@article {pmid40559922, year = {2025}, author = {Zhong, YF and Ding, C and Yao, CJ and Wang, JC and Feng, MQ and Gong, XX and Yu, L and Xu, HD and Xia, HL}, title = {HMGB1 as a Key Mediator in Malignant Mesothelioma and a Potential Target for Asbestos-Related Cancer Therapy.}, journal = {Toxics}, volume = {13}, number = {6}, pages = {}, pmid = {40559922}, issn = {2305-6304}, support = {202413023017//National Innovation Training Program for College Students/ ; 2020KY100//Medical Science and Technology Project of Zhejiang Province/ ; YS2022011//Institutional Special Program for Healthy Zhejiang/ ; First Class, Category A//Key Discipline of Zhejiang Province in Public Health and Preventive Medicine/ ; }, abstract = {Malignant mesothelioma (MM) is a highly aggressive cancer strongly associated with asbestos exposure, and accumulating evidence suggests that high mobility group box 1 (HMGB1) plays a central role in its pathogenesis. Our in vitro and in vivo experiments revealed that HMGB1 was highly expressed in MM. Both genetic and pharmacological inhibition of HMGB1 markedly suppressed MM cell viability, migration, and invasion, while inducing G1-phase cell cycle arrest and enhancing apoptosis. Interestingly, the inhibition of Toll-like receptor 4 (TLR4), achieved through both siRNA and TAK-242 treatment, not only suppressed tumor-promoting signals but also reduced HMGB1 expression, suggesting a self-amplifying HMGB1-TLR4 loop. Mechanistically, in vitro experiments indicated that suppression of HMGB1 and TLR4 was associated with decreased activation of NF-κB, AKT, and ERK pathways, which are involved in regulating MM cell survival and motility. In xenograft models, treatment with ethyl pyruvate (EP) and TAK-242 significantly suppressed tumor growth and HMGB1 expression, reinforcing their therapeutic potential. Given HMGB1's influence on both tumor cell behavior and the immune microenvironment, targeting the HMGB1-TLR4 axis may not only provide a novel therapeutic strategy for MM but also offer insights into the mechanisms underlying asbestos-induced tumorigenesis, potentially guiding future prevention and intervention strategies in asbestos-exposed populations.}, } @article {pmid40559443, year = {2025}, author = {Rovers, S and Farahmand, P and Liu, D and Brants, L and Hermans, C and Peeters, D and McKinven, D and Doig, J and Lardon, F and van Meerbeeck, J and Marcq, E and Murphy, DJ and Smits, E}, title = {A Minimally Invasive Transthoracic Injection Technique for Reproducible Intrapleural Delivery in Mice.}, journal = {Methods and protocols}, volume = {8}, number = {3}, pages = {}, doi = {10.3390/mps8030055}, pmid = {40559443}, issn = {2409-9279}, support = {OZ8119//Kom op tegen Kanker/ ; FFB210293//BOF research fund University of Antwerp/ ; A29372/CRUK_/Cancer Research UK/United Kingdom ; EDDPGM-Nov21\100001/CRUK_/Cancer Research UK/United Kingdom ; DCRNPG-Jun22\100007/CRUK_/Cancer Research UK/United Kingdom ; }, abstract = {The development of standardised, reproducible preclinical models is essential for advancing pleural mesothelioma (PM) research. Here, we present a simple and reliable minimally invasive transthoracic intrapleural injection technique that could improve the efficiency of orthotopic PM model generation. By incorporating a simple needle sleeve to control the injection depth, this method eliminates the need for surgery or general anaesthesia, reducing technical complexity and animal stress while ensuring precise delivery into the pleural cavity. We demonstrate the effectiveness of this approach by achieving a 100% tumour engraftment rate following the injection of AE17 tumour cells. Additionally, this technique has been successfully used for asbestos fibre injection in mesothelioma models, highlighting its versatility. By providing a more accessible, standardised alternative to existing methods, this protocol improves the reliability of PM models and facilitates broader adoption by researchers, including those with limited experience in invasive procedures.}, } @article {pmid40544502, year = {2025}, author = {Adamic, K and Malovrh, MM and Stojkovic, UB and Rozman, A}, title = {Fibulin-3 in plasma and pleural effusion as a biomarker of mesothelioma.}, journal = {Radiology and oncology}, volume = {59}, number = {2}, pages = {225-232}, pmid = {40544502}, issn = {1581-3207}, mesh = {Humans ; Male ; Female ; *Extracellular Matrix Proteins/blood/metabolism/analysis ; *Biomarkers, Tumor/blood/metabolism ; Middle Aged ; Aged ; *Mesothelioma/blood/diagnosis/pathology/metabolism/mortality ; Prospective Studies ; Mesothelioma, Malignant ; *Pleural Neoplasms/blood/diagnosis/pathology/metabolism ; *Lung Neoplasms/blood/diagnosis/pathology ; *Pleural Effusion/metabolism/blood ; *Pleural Effusion, Malignant/blood/metabolism ; Prognosis ; Aged, 80 and over ; Adult ; Sensitivity and Specificity ; ROC Curve ; Enzyme-Linked Immunosorbent Assay ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a global health concern linked to asbestos exposure. In Slovenia, regions with high asbestos exposure rates make MPM a significant public health issue. Although thoracoscopic biopsy is the gold standard for MPM diagnosis, its invasiveness highlights the need for reliable, non-invasive diagnostic biomarkers.

PATIENTS AND METHODS: This prospective study evaluated the diagnostic potential of fibulin-3 as a biomarker for MPM, focusing on its ability to distinguish MPM from other pleural conditions, its association with disease stage and histological subtype, and its prognostic value for survival. Ninety patients, who underwent diagnostic thoracoscopic biopsy from January 2013 to October 2014, were included. Fibulin-3 levels in plasma and pleural effusion were measured using enzyme-linked immunosorbent assay (ELISA), and clinical data were analysed with statistical tests, including receiver operating characteristic (ROC) analysis.

RESULTS: The study cohort comprised 32 patients with MPM, 24 with metastatic pleural carcinoma, and 34 with benign pleural diseases. Plasma fibulin-3 levels were significantly elevated (p = 0.0132) in MPM patients compared to those with benign pleural effusions due to asbestos exposure, with a cut-off of 12.31 ng/mL showing 100% specificity but low sensitivity (39.39%). Elevated fibulin-3 levels in pleural effusion correlated with advanced disease (p = 0.0463) and aggressive histological subtypes (p = 0.0324). No significant survival correlation was observed.

CONCLUSIONS: While plasma fibulin-3 is a highly specific biomarker for MPM, its low sensitivity limits its standalone diagnostic utility. Its potential role in risk stratification and early detection of MPM at-risk populations using combination of different and new biomarkers warrants further study.}, } @article {pmid40520135, year = {2025}, author = {Singh, R and Frank, AL}, title = {Work‑Related Migration to the Alang Ship‑Breaking Industry from Other Parts of India: An Overview of Health‑Related Issues.}, journal = {Annals of global health}, volume = {91}, number = {1}, pages = {32}, pmid = {40520135}, issn = {2214-9996}, mesh = {Humans ; India/epidemiology ; *Ships ; *Occupational Exposure/adverse effects ; *Asbestos/adverse effects ; *Transients and Migrants/statistics & numerical data ; *Mesothelioma/epidemiology/etiology ; Male ; Adult ; Female ; Middle Aged ; }, abstract = {Background: India has a ship‑breaking yard at Alang in Gujarat. The workers are prone to being exposed to various hazardous chemicals, including asbestos. These workers are often interstate migrants, and there is a chance of them developing diseases caused by asbestos, manifesting decades after exposure. This includes mesothelioma, which is a malignancy caused by asbestos exposure and can manifest much after the cessation of their employment. Objective: In the absence of an operational national database of migrants, it is important to understand the source of migrants to trace future disease occurrence, especially after retiring to their home states. This study aims to find the Indian districts from which workers migrate to work at Alang‑Sosiya ship‑breaking yards. Methods: The current study uses the Right to Information Act, 2005, to find out the districts of residents of migrant workers that came to Alang in 2019 as a representative year. Findings and conclusion: The data point to districts in three states: Uttar Pradesh, Jharkhand and Bihar, and have important policy consequences and epidemiological importance as these can be used to understand the aetiology of asbestos‑related diseases.}, } @article {pmid40518258, year = {2025}, author = {Lee, CT and Gandhi, SA and Elmrayed, S and Barnes, H and Lorenzetti, D and Salisbury, ML and Stewart, ID and Barber, C and Peters, CE and Feary, J and Johannson, KA}, title = {Inhalational exposures associated with risk of interstitial lung disease: a systematic review and meta-analysis.}, journal = {Thorax}, volume = {}, number = {}, pages = {}, doi = {10.1136/thorax-2024-222306}, pmid = {40518258}, issn = {1468-3296}, abstract = {RATIONALE: Inhalational exposures are associated with risk of developing interstitial lung disease (ILD), yet the relationship between specific exposures and ILD is poorly characterised.

OBJECTIVE: Identify inhalational exposures associated with ILD and estimate the effects of exposures on ILD risk.

METHODS: MEDLINE and EMBASE databases were searched from 1990 to 2022 to identify inhalational exposures associated with ILD diagnosis. ILDs where causality is well-established (hypersensitivity pneumonitis, pneumoconiosis) and sarcoidosis were excluded. Two independent reviewers screened abstracts with full-text review and data extraction of eligible studies. Where possible, data were pooled and multilevel meta-analysis was specified using a random effects model. Sources of heterogeneity and risk of bias were assessed.

MAIN RESULTS: 96 studies were included in the systematic review, representing 40 819 116 subjects (295 167 had ILD, 40 523 949 controls). For the meta-analysis, 54 studies were included (40 490 793 subjects: 273 899 ILD, 40 216 894 controls). Exposures associated with significantly increased ILD risk included smoking (OR 1.69, 95% CI 1.47 to 1.94), organic exposures (OR 1.56, 95% CI 1.12 to 2.16), metals (OR 1.52, 95% CI 1.07 to 2.16), dust (OR 1.45, 95% CI 1.20 to 1.76) and asbestos (OR 1.53, 95% CI 1.08 to 2.15). Silica and fumes had positive associations with ILD that trended towards significance.

CONCLUSIONS: This systematic review and multilevel meta-analysis is the first to comprehensively assess the effect of inhalational exposures on overall risk of ILD, with multiple putative exposures identified. Future work should investigate novel occupational exposures associated with ILD, characterise the gene-environment interaction and develop preventative strategies.

PROSPERO REGISTRATION NUMBER: CRD42022292908.}, } @article {pmid40515516, year = {2025}, author = {Chen, G and Mannetje, A' and Salmond, JA and Douwes, J}, title = {Environmental and occupational exposure to erionite and related health risks: progress and prospects.}, journal = {Annals of work exposures and health}, volume = {}, number = {}, pages = {}, doi = {10.1093/annweh/wxaf034}, pmid = {40515516}, issn = {2398-7316}, support = {//New Zealand Ministry of Business, Innovation and Employment/ ; }, abstract = {OBJECTIVES: Erionite, a naturally occurring fibrous zeolite classified as a human carcinogen, is believed to be more potent than asbestos in causing mesothelioma. However, unlike asbestos, erionite has rarely been used for commercial purposes and, as a result, knowledge about exposure pathways is limited. This paper provides a narrative review of the current knowledge regarding the associations between erionite exposure, health effects and exposure circumstances.

METHODS: Medline/PubMed and Scopus were systematically searched up to the end of 2024 using keywords related to erionite exposure and health outcomes.

RESULTS: We identified 26 peer-reviewed journal articles reporting on the health effects of erionite exposure, specifically mesothelioma and lung cancer, with mesothelioma being the most extensively studied outcome. Of these, 12 studies focussed on erionite-exposed populations in Turkey, 8 examined health effects among Turkish migrants in northern Europe, and 6 investigated erionite-related health risks in North America (3 in the United States and 3 in Mexico). These studies showed a very high incidence of mesothelioma, often in relatively young individuals, from the Cappadocia region of Turkey, with well-documented environmental exposures to erionite, contributing to a high proportion of all deaths (21% to 51%) in affected villages. Evidence of lung cancer associated with erionite exposure was also found. There is also evidence of erionite exposure-associated mesothelioma in Guanajuato, central Mexico. In the United States, erionite exposure-associated health effects (not mesothelioma) have been reported among people occupationally exposed to erionite. Studies on environmental exposures have shown outdoor concentrations ranging from 0.001 f/ml to 0.3 f/ml, while indoor concentrations have ranged from 0.005 to 1.38 f/ml. Occupational exposure to erionite has been less studied, with only one study in forestry workers showing elevated exposures to erionite ranging from non-detectable to 0.36 f/cc. Erionite deposits have also been identified in other countries such as Italy and New Zealand, but exposures and associated health effects have not yet been studied in these regions.

CONCLUSION: There is clear evidence that environmental exposure to erionite in the Cappadocia region of Turkey, and Guanajuato in central Mexico are causally associated with the high mesothelioma rates observed in these areas. Evidence for other parts of the world where there is naturally occurring erionite is limited. This review has highlighted significant knowledge gaps, and advocates for further research on occupational exposure to erionite fibres and associated health effects.}, } @article {pmid40506895, year = {2025}, author = {Zahiu, T and Mihu, CM and Bosca, BA and Mărginean, M and Mocan, LP and Ștefan, RA and Suflețel, RT and Mihu, C and Melincovici, CS}, title = {Molecular Insights into Pleural Mesothelioma: Unveiling Pathogenic Mechanisms and Therapeutic Opportunities.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {15}, number = {11}, pages = {}, doi = {10.3390/diagnostics15111323}, pmid = {40506895}, issn = {2075-4418}, abstract = {Pleural mesothelioma (PM) is a rare disease, which is going to be a global medical concern in the 21st century, because of its aggressiveness, late diagnosis, and insufficient therapies. This review seeks to enhance the comprehension of medical professionals regarding the risk factors and environmental influences that contribute to the development of the disease, as well as its underlying mechanisms. In addition, we aim to provide a schematic yet thorough overview of diagnostic techniques in PM, emphasizing the significance of the immunohistochemical markers BAP1 and MTAP, with the latter serving as an almost ideal surrogate for the gold-standard diagnostic approach, FISH p16/CDKN2A deletion. The scientific world is grappling with BAP1, MTAP, and the tumour inflammatory microenvironment, because they are the key for personalized treatments and palliative care in this disease. Considering that the survival rate for patients with PM seldom surpasses five years, every moment is significant. Therefore, our article also highlights recent advancements in clinical assessments related to prognostic scoring and treatment options. PM is a complex disease, with gradual progression over decades, which requires further investigation covering the prevention, mutations, diagnosis and treatment.}, } @article {pmid40506494, year = {2025}, author = {Yang, J and Kong, F}, title = {[Recent Advances in Medical Treatment of Malignant Pleural Mesothelioma].}, journal = {Zhongguo fei ai za zhi = Chinese journal of lung cancer}, volume = {28}, number = {5}, pages = {391-399}, doi = {10.3779/j.issn.1009-3419.2025.102.18}, pmid = {40506494}, issn = {1999-6187}, mesh = {Humans ; Mesothelioma, Malignant ; *Pleural Neoplasms/therapy/drug therapy ; *Lung Neoplasms/therapy/drug therapy ; }, abstract = {Malignant pleural mesothelioma (MPM) is a highly aggressive malignancy originating from mesothelial cells of the pleura, primarily associated with asbestos exposure, and is often characterized by poor prognosis. Due to the lack of specific clinical manifestations in the early stages, the diagnosis of MPM presents a significant challenge, leading to most patients being diagnosed at an advanced stage, which limits the effectiveness of surgical treatment. Consequently, systemic therapies are commonly required. Although Pemetrexed in combination with Platinum-based chemotherapy remains the first-line standard treatment for unresectable MPM, its therapeutic efficacy is limited, and more effective treatment strategies are urgently needed. In recent years, immune checkpoint inhibitors have made significant progress in the treatment of MPM, markedly improving patient survival outcomes. With the increasing depth of molecular biological research on MPM, targeted therapies offer promising personalized treatment options. Additionally, the therapeutic potential of novel strategies such as cell therapy and oncolytic virus therapy is beginning to emerge. This review summarizes the latest advancements in the medical treatment of MPM and looks forward to future therapeutic directions, aiming to provide insights for clinical practice. .}, } @article {pmid40502637, year = {2025}, author = {Zhao, T and Hu, X and Peng, M and Wei, W and Fu, N and Chen, C and Chen, Z}, title = {Volatile organic compounds in exhaled human breath for the diagnosis of malignant pleural mesothelioma: a meta-analysis.}, journal = {Frontiers in oncology}, volume = {15}, number = {}, pages = {1537767}, pmid = {40502637}, issn = {2234-943X}, abstract = {OBJECTIVE: Malignant pleural mesothelioma (MPM) is a relatively rare thoracic tumor with a high mortality rate, making early diagnosis and treatment challenging. The present study evaluated the utility of exhaled volatile organic compounds (VOCs) in diagnosing MPM.

METHODS: The Cochrane Library, PubMed, EMBASE, and Web of Science were systematically searched for clinical trials assessing the diagnostic ability of VOCs for MPM through August 30, 2024. Quality was evaluated using the QUADAS-2 tool. A meta-analysis was performed with a bivariate model for sensitivity and specificity using Stata MP 17.0 software.

RESULTS: Eight trials with 859 subjects were included. VOCs were found to have a pooled sensitivity of 0.86 (95% confidence interval [CI] 0.75-0.93), a pooled specificity of 0.73 (95% CI 0.58-0.84), and an area under the curve (AUC) of 0.88 (95% CI 0.85-0.90) in differentiating MPM patients from healthy controls. In addition VOCs had a pooled sensitivity of 0.89 (95% CI 0.83-0.93), a pooled specificity of 0.79 (95% CI 0.57-0.91), and an AUC of 0.91 (95% CI 0.88-0.93) in differentiating MPM patients from asymptomatic individuals formerly exposed to asbestos (AEx).

CONCLUSIONS: Although the utility of VOCs in diagnosing MPM varied among clinical trials, VOCs in exhaled human breath may have a potential role in the diagnosis of MPM. Large-scale randomized clinical trials are warranted.}, } @article {pmid40501447, year = {2025}, author = {Karam, AS and Abdelwahab, S and Ezz El Din, MMA and Alorabi, MO}, title = {A randomized comparative study on maintenance gemcitabine versus supportive care in pleural mesothelioma.}, journal = {Future oncology (London, England)}, volume = {}, number = {}, pages = {1-11}, doi = {10.1080/14796694.2025.2516412}, pmid = {40501447}, issn = {1744-8301}, abstract = {BACKGROUND: Pleural mesothelioma (PPM) is a rare aggressive cancer linked to asbestos exposure, with limited treatment options, especially in low-resource settings. While immune checkpoint inhibitors show promise, access remains limited in many countries.

METHODS: This prospective study was conducted at Ain Shams University Hospital from November 2022 to December 2024. 42 patients with unresectable PM and no progression after 4-6 cycles of platinum-pemetrexed chemotherapy were randomized 1:1 to receive switch-maintenance gemcitabine (1000 mg/m[2] on days 1 and 8 every 21 days) or best supportive care (BSC). Progression-free survival (PFS), overall survival (OS), and toxicity (Common Terminology Criteria for Adverse Events CTCAE v5.0) were assessed.

RESULTS: Maintenance gemcitabine significantly improved PFS in unresectable PM (8.9 vs. 5.2 months, p = 0.022), confirmed in univariate analysis (HR = 0.505, p = 0.040) but not multivariate (p = 0.069). OS also favored gemcitabine (16.2 vs. 13.4 months, p = 0.138). Multivariate analysis linked gemcitabine (p = 0.043), females, cisplatin use, and partial response to initial therapy with better OS, while ECOG II and occupational exposure predicted worse OS. Adverse events were manageable.

CONCLUSION: Maintenance gemcitabine significantly improved PFS and was well tolerated, offering a practical and affordable treatment option for PM.

CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifier is NCT05660616.}, } @article {pmid40498282, year = {2025}, author = {Aujayeb, A and Astoul, P}, title = {A Diagnostic Approach to Malignant Pleural Mesothelioma.}, journal = {Pulmonary therapy}, volume = {}, number = {}, pages = {}, pmid = {40498282}, issn = {2364-1746}, abstract = {In this concise article, we give a current overview of the practical approach to diagnosing pleural mesothelioma (PM). PM is a rare, incurable, aggressive cancer almost exclusively related to previous asbestos exposure. We begin by outlining the general approach to pleural malignancy. The focus then shifts to pleural mesothelioma (PM), with discussions on cytological analyses, a direct-to-thoracoscopy approach, specialist services, and future directions. This narrative review aims to provide an updated, practical overview of current and emerging diagnostic strategies.}, } @article {pmid40489775, year = {2025}, author = {Zisook, RE and Gaffney, SH and Pierce, JS and Comerford, CE and Hamaji, CM and Henshaw, JL and Balzer, JL}, title = {A state-of-the-science review of health hazards in insulators in the United States.}, journal = {Journal of occupational and environmental hygiene}, volume = {}, number = {}, pages = {1-104}, doi = {10.1080/15459624.2025.2488390}, pmid = {40489775}, issn = {1545-9632}, abstract = {This article presents a state-of-the-science analysis of the evolution of knowledge over time regarding the potential health hazards associated with exposure to airborne asbestos among the insulating trade, which included the state of knowledge of the International Association of Heat and Frost Insulators and Asbestos Workers Union (IAHFIAW), now known as the International Association of Heat and Frost Insulators and Allied Workers (IAHFIAW), and its connection to the National Insulation Contractors Association (NICA) and the National Insulation Manufacturers Association (NIMA); work practices, exposure controls, and personal protective equipment (PPE) that were recommended; and the major regulations and guidelines related to asbestos over the past 100 years in the United States (U.S.). The general timeline of knowledge regarding potential health hazards associated with insulator exposures to asbestos in the U.S. Navy is incorporated in this review, including specific examples of exposure monitoring, medical surveillance campaigns, and recommendations for work practice controls over time. This paper is divided into five time periods (late 1800s-1945; 1946-1962; 1963-1970; 1971-1981; and 1982-present) that were selected based on what were generally believed to be seminal events with respect to the recognition or knowledge of the hazards of asbestos in relation to the insulating trade, the development and standardization of workplace and respiratory controls, and the promulgation of occupational exposure limits (OELs) for asbestos. For each time period, the following topics are addressed: insulation product composition and usage; major developments in the recognition or knowledge of health hazards of asbestos, including key epidemiology studies; health studies of insulators; guidelines and regulations related to OELs for asbestos and sampling and analytical method development for characterizing exposures; and industrial hygiene sampling and recommendations for controlling exposure to asbestos during insulating operations. The goal of this analysis is to illustrate when specific scientific knowledge about asbestos health hazards was established and communicated among the scientific and industrial hygiene communities and within the IAHFIAW. Although this information is available in various separate documents and locations, the purpose of this work is to synthesize it together in a single document so that the reader can understand the full historical context of the evolution of asbestos health hazard knowledge within the insulator trade. To the best of the authors' knowledge, this review represents the most comprehensive historical examination of the literature on exposure, health effects, and industrial hygiene controls related to asbestos used in insulating operations over time.}, } @article {pmid40487709, year = {2025}, author = {Marsili, D and Binazzi, A and Marinaccio, A and Mensi, C and Fazzo, L and , }, title = {Engaging Social Stakeholders in National Asbestos Research for Public Health: An Italian Experience.}, journal = {Annals of global health}, volume = {91}, number = {1}, pages = {25}, pmid = {40487709}, issn = {2214-9996}, mesh = {Humans ; Italy/epidemiology ; *Asbestos/adverse effects/toxicity ; *Public Health ; *Stakeholder Participation ; *Asbestosis/prevention & control/epidemiology ; *Environmental Exposure/adverse effects/prevention & control ; Mesothelioma/prevention & control/epidemiology ; }, abstract = {Background: Asbestos and its impacts on the population worldwide are threats to the environment and public health, striking both countries that have banned asbestos, such as Italy in 1992, and those that continue its use. In Italy, asbestos‑affected communities have experienced diverse progress in their involvement in prevention and asbestos risk management. Objectives: Exploring social stakeholders' engagement in research projects on asbestos health impacts and discussing the benefits of the ongoing SEPRA project (Epidemiological Surveillance, Prevention and Research on Asbestos). Methods: A structured communication plan was implemented, including the selection of social stakeholders and their engagement during the project's lifetime; selection of research topics to characterize the participative initiatives and communication modality; and collection and analysis of inputs for enabling impacts. Findings: Sharing major issues of concern highlighted by social stakeholders, such as the recognition of all asbestos‑related diseases besides mesothelioma and non‑occupational asbestos exposures. The need to implement health surveillance plans in all the regions of the country, including a national plan addressing the psychological support to patients and their families, and to extend social welfare to people affected by occupational and non‑occupational asbestos‑related diseases has been highlighted. Conclusions: Social stakeholders' engagement in research activities through structured interactions and trusted relationships allowed us to share information, needs and recommendations for implementing effective actions in public health. Researchers committed to asbestos research at a national scale should closely collaborate with stakeholders through structured communication, considering their diversified fields of experience, critical thinking and inputs. Giving recognition to social stakeholders of their role and expertise and providing them appropriate tools to interact with the relevant authorities and the asbestos‑affected communities are key for effectively advancing in inclusive processes and health equity.}, } @article {pmid40487392, year = {2025}, author = {Shi, L and Yuan, D and Zhu, F and He, Y and Zuo, R and Chen, L and Luo, Y and Wang, Y and Huang, D and Chen, P and Guo, H}, title = {Immune-related gene risk model establishment and role of key gene FUCA1 in malignant pleural mesothelioma.}, journal = {Frontiers in pharmacology}, volume = {16}, number = {}, pages = {1577232}, pmid = {40487392}, issn = {1663-9812}, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare type of tumor closely associated with asbestos exposure. Increasing evidence shows that high immuno-heterogeneity reduces the therapeutic efficacy of MPM. At present, good biomarkers to screen immunodominant populations and predict the efficacy of immunotherapy are lacking.

METHODS: In this study, expression data from TCGA, GSE2459, GSE51024, and GSE29354 were integrated for model construction. An eight-gene risk score model (FLI1, IL32, FUCA1, CCR2, PSMB10, CCL5, WT1, and KRT5) was constructed using CIBERSORT, weighted gene co-expression network analysis, Cox regression analysis, differentially expressed gene analysis, and protein-protein interaction network. The K-M survival analysis was used to evaluate the prediction ability of the risk score model. The TIDE database and Oncology Drug Sensitivity Genomics database were used to assess the predictive power of risk score models for treatment. In addition, the expression of the key gene in para-carcinoma tissue and MPM samples were detected by Immunohistochemistry. Patient clinical information was employed to evaluate the relationship between key genes and patient survival. Finally, the biological functions of the key gene were examined by in vitro and in vivo experiments.

RESULTS: The score model was used to divide patients with MPM into low- and high-risk groups. The high-risk group was characterized by a survival disadvantage, and they were less sensitive to immunotherapy. Clinical data suggest that FUCA1, which is a key gene in the model, is an independent risk factor for predicting the prognosis of patients with MPM. A series of experiments demonstrated that FUCA1 expression was negatively correlated with the proliferation, invasion and migration abilities of MPM cells. Further studies revealed that FUCA1 inhibited epithelial-mesenchymal transition in MPM cells by regulating the PI3K-AKT signaling pathway.

CONCLUSION: The risk score model provides a new perspective for screening potential populations to benefit from immunotherapy and predicting their survival. FUCA1 may be a potential prognostic biomarker and promising therapeutic target for patients with MPM.}, } @article {pmid40484892, year = {2025}, author = {Orozco-Castaño, C and Mejía-Garcia, A and Tsao, HM and Bonilla, DA and Bruges-Maya, R and Combita, A and Parra-Medina, R}, title = {Transcriptional landscape of pleural mesothelioma patients in relation to NF2 gene mutational status.}, journal = {Journal of the Egyptian National Cancer Institute}, volume = {37}, number = {1}, pages = {25}, pmid = {40484892}, issn = {2589-0409}, mesh = {Humans ; *Mutation ; Female ; Male ; *Neurofibromin 2/genetics ; Middle Aged ; *Mesothelioma/genetics/pathology/drug therapy/mortality ; *Pleural Neoplasms/genetics/pathology/drug therapy/mortality ; Prognosis ; Aged ; Mesothelioma, Malignant/genetics ; Biomarkers, Tumor/genetics ; Gene Expression Regulation, Neoplastic ; Transcriptome ; Tumor Microenvironment/genetics ; Gene Expression Profiling ; Adult ; }, abstract = {BACKGROUND: Pleural mesothelioma (PM) is an aggressive cancer with poor prognosis, often driven by asbestos exposure. Mutations in the NF2 gene, a key regulator of the Hippo signaling pathway, are frequently observed in PM. However, their impact on tumor biology, immune infiltration, cytokine signaling, and therapeutic response remains poorly understood.

METHODS: Using data from The Cancer Genome Atlas, we analyzed 82 PM cases to assess the prevalence and consequences of NF2 mutations. Logistic regression was used to evaluate associations with clinical variables, while transcriptomic differences were examined through differential expression and functional enrichment analyses. Immune and stromal infiltration were inferred via the xCell algorithm, cytokine signaling analyzed with Cytosig, and chemotherapeutic sensitivity predicted using the pRRophetic R package. Single-cell RNA sequencing data provided further insights into transcriptional patterns in NF2-mutated tumors.

RESULTS: NF2 mutations were present in 22% of cases, with no significant correlations to histological subtype, stage, or age. NF2-mutated tumors exhibited increased infiltration of basophils, naïve B cells, and pericytes, along with altered cytokine profiles, including NRG1, TGFB3, and reduced FGF2. Differentially expressed genes, such as MYL7 and HOXA11, were linked to poorer survival. Chemotherapy modeling indicated higher sensitivity to camptothecin and vinblastine in NF2-mutated tumors.

CONCLUSIONS: NF2 mutations influence the tumor microenvironment, transcriptional landscape, and predicted therapeutic response in PM, underscoring their potential as prognostic biomarkers. These findings support tailored therapeutic strategies targeting NF2-related pathways, including Hippo signaling and cytokine modulation.}, } @article {pmid40475198, year = {2025}, author = {Patel, K and Tuminello, S and Taioli, E}, title = {Sex differences in asbestos exposure.}, journal = {Frontiers in public health}, volume = {13}, number = {}, pages = {1588415}, pmid = {40475198}, issn = {2296-2565}, mesh = {Humans ; *Asbestos/adverse effects ; Female ; Male ; *Occupational Exposure/statistics & numerical data/adverse effects ; Sex Factors ; *Environmental Exposure/statistics & numerical data/adverse effects ; *Mesothelioma/epidemiology ; Mesothelioma, Malignant ; }, abstract = {BACKGROUND: Although the association between exposure to asbestos and malignant mesothelioma has been established, occupational exposure has been historically present in males, while the ascertainment of female exposures is more nuanced. We reviewed the literature to assess differences in environmental exposure in mesothelioma cases according to sex.

METHODS: A new PubMed search was conducted with the key words "mesothelioma" and "environmental exposure" on October 11, 2024 with a start date of January 1, 2016, to supplement our previous qualitative review that included publications up through June 2016. Studies conducted in occupational settings were excluded.

RESULTS: Out of the 26 eligible papers, 11 were excluded because they did not report information on exposure by sex, leaving 15 published studies that were added to the 9 from our previous qualitative synthesis (24 total studies). 19 studies were cross-sectional, 2 were cohort and 3 were case control studies. The average NIH Study Quality tool score was 7.4/14 (minimum 3, maximum 12). Occupational exposure was more frequently observed in males than in females. While a male to female ratio favored males, there was variation in the strength of the association. There was a large proportion of cases with "unknown exposure," and these were more frequently observed among female cases. In some studies, up to 40% of female cases had unknown exposure profiles. Quality assessment showed a generalized lack of standardization in the definition of environmental exposures across studies.

CONCLUSION: Although recent studies have continued to improve our understanding of environmental exposure to asbestos and other elongated fibers, challenges remain, including but not limited to lack of rigorous, high-quality evidence and difficulty standardizing definitions across countries and datasets to enable appropriate comparison across studies.}, } @article {pmid40474647, year = {2025}, author = {Ichiyama, N and Yamane, H and Saitou, T and Miura, M and Mimura, A and Kosaka, Y and Kawahara, T and Nagasaki, Y and Ochi, N and Nakanishi, H and Fujiwara, H and Takigawa, N}, title = {A Case of Duodenal Metastasis From Malignant Pleural Mesothelioma Diagnosed by Gastrointestinal Endoscopy Following Progressive Anemia During Salvage Chemotherapy.}, journal = {Thoracic cancer}, volume = {16}, number = {11}, pages = {e70098}, doi = {10.1111/1759-7714.70098}, pmid = {40474647}, issn = {1759-7714}, mesh = {Humans ; *Mesothelioma, Malignant/pathology/drug therapy/complications ; *Salvage Therapy/methods ; *Duodenal Neoplasms/secondary ; Male ; *Pleural Neoplasms/pathology/drug therapy ; *Endoscopy, Gastrointestinal/methods ; *Anemia/pathology ; Middle Aged ; Aged ; *Lung Neoplasms/pathology/drug therapy ; }, abstract = {Malignant pleural mesothelioma (MPM) primarily progresses through direct invasion into the lung and pleura and is a refractory tumor in which asbestos exposure is a major underlying factor in most cases. Hematogenous metastasis of MPM is not uncommon in advanced stages, and reports suggest that metastatic sites may impact prognosis. Gastrointestinal metastases, ranging from the stomach to the colon, have been sporadically observed, but metastases to the small intestine and duodenum are exceedingly rare. Here, we report a case in which duodenal metastasis of MPM was endoscopically identified during the patient's lifetime while undergoing salvage chemotherapy following treatment with an immune checkpoint inhibitor and cytotoxic chemotherapy. Given the rarity and clinical significance of such cases, we present this report with a review of the relevant literature.}, } @article {pmid40464221, year = {2025}, author = {Li, J and Dai, Y and Huang, H and Zhong, Y and Zhu, L}, title = {Studies on the regulatory role of microRNA-30d in chrysotile-transformed MeT-5A cells.}, journal = {Toxicology and industrial health}, volume = {}, number = {}, pages = {7482337251342903}, doi = {10.1177/07482337251342903}, pmid = {40464221}, issn = {1477-0393}, abstract = {Asbestos is classified as a class I carcinogen by the International Agency for Research on Cancer (IARC) because of its propensity to accumulate in the lungs and induce malignant tumors, including lung cancer and malignant mesothelioma. The objective of this study was to examine the inhibitory impact of miR-30d on the proliferation, migration, and invasion of chrysotile-transformed human pleural mesothelial cells (MeT-5A). The asbestos-transformed cell model was constructed using a chrysotile asbestos chronically exposed human pleural mesothelial cell line (MeT-5A). The expression level of miR-30d in the transfected cells was determined by qRT-PCR. Cell viability was assessed by CCK-8 assay. The apoptosis rate was evaluated by flow cytometry. The cell scratch assay and the Transwell assay were used to assess cell migration and invasion ability. It was observed that the expression level of miR-30d in Asb MeT-5A+miR-30d cells transfected with miR-30d mimics was markedly elevated in comparison to that in Asb MeT-5A+miR NC cells. Additionally, the cell viability in Asb MeT-5A+miR-30d cells was significantly diminished, while the level of apoptosis was markedly elevated in comparison to that in Asb MeT-5A+miR NC cells. The relative migration area was significantly lower in the Asb MeT-5A+miR-30d group than in the Asb MeT-5A+miR NC group. Furthermore, the number of migrated and invaded cells in the Asb MeT-5A+miR-30d group was significantly less than in the Asb MeT-5A+miR NC group. The findings suggest that miR-30d may suppress the proliferation, apoptosis, migration, and invasion of chrysotile-transformed pleural mesothelial cells.}, } @article {pmid40439143, year = {2025}, author = {Rovers, S and Van Audenaerde, J and Verloy, R and De Waele, J and Brants, L and Hermans, C and Lau, HW and Merlin, C and Möller Ribas, M and Ponsaerts, P and Van Laere, S and Lardon, F and Wouters, A and Fisher, SA and van Meerbeeck, J and Marcq, E and Smits, E}, title = {Co-targeting of VEGFR2 and PD-L1 promotes survival and vasculature normalization in pleural mesothelioma.}, journal = {Oncoimmunology}, volume = {14}, number = {1}, pages = {2512104}, pmid = {40439143}, issn = {2162-402X}, mesh = {Animals ; *B7-H1 Antigen/antagonists & inhibitors ; *Vascular Endothelial Growth Factor Receptor-2/antagonists & inhibitors ; Mice ; *Pleural Neoplasms/drug therapy/pathology/blood supply/immunology/metabolism ; Mice, Inbred C57BL ; *Immune Checkpoint Inhibitors/pharmacology ; *Neovascularization, Pathologic/drug therapy ; Humans ; *Mesothelioma/drug therapy/pathology/blood supply/immunology/metabolism ; Cell Line, Tumor ; Angiogenesis Inhibitors/pharmacology ; Female ; Lymphocytes, Tumor-Infiltrating/immunology/drug effects ; Disease Models, Animal ; CD4-Positive T-Lymphocytes/immunology/drug effects ; }, abstract = {Pleural mesothelioma (PM) is an aggressive cancer caused by asbestos exposure, with limited treatment options and poor prognosis, highlighting the need for more effective therapies. Combining immune checkpoint blockade with anti-angiogenic therapy has shown potential in other cancers. Our study investigated the combined inhibition of PD-L1 and VEGFR2 in a mouse model of PM. Using C57BL/6 mice with subcutaneous AE17 mesothelioma tumors, we assessed the effects of anti-PD-L1 therapy with induction, concomitant, or consolidation anti-VEGFR2 treatment. Mice received intraperitoneal doses every three days for three treatments. Tumor growth, survival, tumor-infiltrating immune cells and intra-tumoral vasculature were analyzed. Results demonstrated that combining anti-PD-L1 with induction or concomitant anti-VEGFR2 significantly delayed tumor growth, improved survival, and promoted vascular maturation. Flow cytometry suggested T cell exhaustion in monotherapy groups, while no significant changes were seen with concomitant treatment. Depleting CD4[+] T cells reversed the positive effects of concomitant treatment. These findings suggest that dual inhibition of PD-L1 and VEGFR2 is a promising therapeutic approach for PM, with CD4[+] T cells playing a critical role in the immune response. This dual targeting of immune checkpoints and angiogenesis offers a potential new avenue for improving outcomes in PM treatment and warrants further clinical exploration.}, } @article {pmid40438058, year = {2025}, author = {Barlow, CA and Mossman, BT}, title = {Cellular defense mechanisms against asbestos fibers.}, journal = {Frontiers in public health}, volume = {13}, number = {}, pages = {1566473}, pmid = {40438058}, issn = {2296-2565}, mesh = {Humans ; *Asbestos/toxicity/adverse effects ; *Occupational Exposure/adverse effects ; Apoptosis ; Oxidative Stress ; }, abstract = {Although inhalation of sufficient doses and dimensions of airborne asbestos dusts in an occupational setting can produce cancer in the lungs, pleura and peritoneum, tumors occur in <5-10% of exposed individuals, even among persons with considerable historical exposures. In this perspective, we review cell defense mechanisms that are involved in protective and adaptive responses to asbestos exposure. These adaptive responses are orchestrated through a multifaceted cellular program involving the concerted action of diverse stress response pathways, including antioxidant responses, DNA repair mechanisms, molecular mechanisms for intracellular signaling leading to proliferation, apoptosis, and inflammation, and cell cycle regulation. These cell defenses suggest that humans can adjust to moderate levels of stress or change without experiencing negative effects, implying the existence of a threshold dose. Likewise, reported no-observed adverse-effect levels (NOAELs) for various asbestos fiber types and asbestos-related cancers in experimental and epidemiological data further support the existence of a threshold dose and are discussed here.}, } @article {pmid40433487, year = {2025}, author = {Goodman, JE and Korchevskiy, A and Wylie, AG}, title = {Comparison of various methodological approaches to model asbestos thresholds for mesothelioma.}, journal = {Frontiers in public health}, volume = {13}, number = {}, pages = {1569343}, pmid = {40433487}, issn = {2296-2565}, mesh = {Humans ; *Mesothelioma/chemically induced/epidemiology ; *Asbestos/toxicity/adverse effects ; Dose-Response Relationship, Drug ; SEER Program ; Models, Statistical ; Asbestos, Amphibole ; Occupational Exposure/adverse effects ; }, abstract = {BACKGROUND: There is evidence to support several modes of action (MoAs), and particularly non-genotoxic MoAs, for mesothelioma induced by asbestiform elongate mineral particles (EMPs). In turn, these MoAs provide biological support for dose-response relationships that are non-linear and that include a threshold. However, statistical models of human data have not adequately addressed threshold dose-response relationships for asbestiform EMPs and mesothelioma. In addition, unlike other carcinogens, asbestiform EMPs are not uniform materials and display a range of properties.

OBJECTIVES: Our objective was to review various approaches for applying threshold dose-response models to asbestiform EMPs and mesothelioma.

MATERIALS AND METHODS: We collected data from several sources, including the Surveillance, Epidemiology, and End Results (SEER) Program and published case-control studies, cohort studies, and a meta-analysis that evaluated various mineral types of asbestos and mesothelioma risk. Several threshold-based models were fit to the available data. We also evaluated thresholds for certain fiber characteristics.

RESULTS: Certain characteristics of asbestiform EMPs, such as width, length, and surface area, likely have thresholds for mesothelioma. Theoretical models and models based on epidemiology data supported thresholds. A Monte Carlo evaluation of the threshold hypothesis for mesothelioma in a meta-analysis of occupational exposures to various mineral fiber types, using a cumulative exposure metric, demonstrated the likelihood of a threshold to be 72% for non-textile chrysotile, 80.9% for textile chrysotile, 84% for amosite, and 60% for crocidolite. A multi-stage clonal expansion (MSCE) model applied to the SEER mesothelioma registry data demonstrated a good fit with the inclusion of a threshold by a surrogate predictor of cumulative exposure to amphiboles. Finally, lung burden studies also support a threshold. Our preliminary estimate of a central-tendency cumulative exposure threshold level for non-textile chrysotile is ~90 f/cc-years. Based on our proposed approach, we suggest thresholds of 1.04 f/cc-years for amosite, 0.25 f/cc-years for crocidolite, and 4.3-10.9 f/cc-years for tremolite. Future studies should be conducted to support these estimates.

CONCLUSIONS: While uncertainties remain, many angles of scientific evidence support the existence of mineral-specific thresholds for mesothelioma.}, } @article {pmid40427901, year = {2025}, author = {Moyano-Ariza, LF and Villamizar, G and Henríquez-Mendoza, G and Frank, A and Camero, G}, title = {Epidemiological Trends in Mesothelioma Mortality in Colombia (1997-2022): A Retrospective National Study.}, journal = {International journal of environmental research and public health}, volume = {22}, number = {5}, pages = {}, doi = {10.3390/ijerph22050787}, pmid = {40427901}, issn = {1660-4601}, support = {BPIN code 2020000100366//SISTEMA GENERAL DE REGALÍAS/ ; }, mesh = {Humans ; Colombia/epidemiology ; Male ; Female ; Retrospective Studies ; Middle Aged ; Aged ; Adult ; *Mesothelioma/mortality/epidemiology ; Young Adult ; Aged, 80 and over ; Adolescent ; Mortality/trends ; }, abstract = {BACKGROUND: Mesothelioma is a rare and aggressive cancer primarily caused by asbestos exposure. In Colombia, asbestos use began in 1942, but mortality surveillance remains limited. Long latency periods and poor documentation hinder public health action.

MATERIALS AND METHODS: A retrospective descriptive study was conducted using mortality data from 1997 to 2022 obtained from the National Administrative Department of Statistics (DANE), including all mesothelioma cases recorded under the five ICD-10 diagnostic categories (C45.0 to C45.9), covering all anatomical sites of first occurrence. Variables analyzed included sex, age, occupation, and place of residence. Mortality rates and trends were estimated using R, Excel, JoinPoint, and Minitab.

RESULTS: A total of 1539 mesothelioma deaths were recorded. Most occurred in men (65.1%) and in individuals over 60 years old (62.6%). Urban areas accounted for 92% of deaths. The most frequent diagnosis was unspecified mesothelioma (61.3%). Cities with the highest adjusted mortality rates per 100,000 inhabitants were Sibaté (38.36), Soacha (8.41), and Bogotá (1.89), aligning with historical exposure zones.

CONCLUSIONS: Mesothelioma is still a preventable public health issue in Colombia, with sustained mortality affecting even working-age populations. The high rate of unspecified diagnoses and weak linkage between morbidity and mortality data underscore the need to strengthen diagnostic capacity, improve surveillance, and implement a national asbestos-related disease elimination strategy.}, } @article {pmid40427571, year = {2025}, author = {Kong, SL and Feng, Z and Kim, S and Ha, EK and Kamel, K and Becich, M and Luketich, JD and Pennathur, A}, title = {Hyperthermic Intrathoracic Chemoperfusion and the Role of Adjunct Immunotherapy for the Treatment of Pleural Mesothelioma.}, journal = {Biomolecules}, volume = {15}, number = {5}, pages = {}, doi = {10.3390/biom15050678}, pmid = {40427571}, issn = {2218-273X}, mesh = {Humans ; *Immunotherapy/methods ; *Pleural Neoplasms/therapy/pathology/drug therapy ; *Hyperthermia, Induced/methods ; Combined Modality Therapy ; *Mesothelioma/therapy/pathology ; Mesothelioma, Malignant ; Cytoreduction Surgical Procedures ; }, abstract = {Pleural mesothelioma (PM) is an aggressive cancer originating from the mesothelial lining of the pleura, with a rising global incidence since the mid-20th century due to asbestos and erionite exposure. PM accounts for 80-90% of all mesothelioma cases and is histologically classified into three subtypes-epithelioid, sarcomatoid, and biphasic- with epithelioid carrying the most favorable prognosis. Despite advances in surgery, chemotherapy, radiotherapy, and immunotherapy, PM prognosis remains poor, necessitating more effective, multimodal strategies. Hyperthermic intrathoracic chemoperfusion (HITHOC) has emerged as a promising adjunct to cytoreductive surgery by delivering heated chemotherapy directly to the pleural cavity, potentially improving survival-especially in patients with epithelioid PM. Combining HITHOC with post-surgical immunotherapy represents a novel approach to enhancing both local and systemic anti-tumor responses and targeting microscopic disease and distant metastases. This review explores surgical outcomes after surgery for PM, the therapeutic synergy of HITHOC and immunotherapy, ongoing clinical trials evaluating this multimodal strategy, and its implications for future patient care.}, } @article {pmid40412248, year = {2025}, author = {Zhu, L and Ying, S and Su, X and Yu, W and Yan, K and Shen, W and Hu, S and Jiang, Z and Xia, H and Feng, L and Zeng, Y and Chen, J and Zhang, X and Lou, J}, title = {A four-miRNA signature as a potential biomarker of malignant mesothelioma patients from hand-spinning asbestos exposed area in Eastern China.}, journal = {Ecotoxicology and environmental safety}, volume = {299}, number = {}, pages = {118357}, doi = {10.1016/j.ecoenv.2025.118357}, pmid = {40412248}, issn = {1090-2414}, abstract = {Malignant mesothelioma (MM) is an aggressive malignant tumor of mesothelial origin that develops mainly in the parietal pleura or peritoneum and is strongly associated with asbestos exposure. MicroRNAs (miRNAs) can serve as biomarkers for the in vitro diagnosis of tumors. To investigate the differential expression of miRNAs in MM patients and identify potential diagnostic biomarkers, we sequenced miRNAs in formalin-fixed paraffin-embedded (FFPE) tumor tissues from 85 malignant pleural mesothelioma patients (samples collected between 1998 and 2017), and compared them with adjacent normal tissues, and the expression of four miRNAs was validated using in situ hybridization. Moreover, the expression differences of these four miRNAs in the plasma were also compared between lung cancer (LC) patients, patients with pleural plaques (PP), asbestos-exposed (AE) subjects and healthy controls (196 plasma samples collected from this handing-spun asbestos-exposed area) by qPCR. We found a total of 31 differentially expressed miRNAs in the tumor tissue of mesothelioma patients compared with the adjacent normal tissue, with 18 upregulated miRNAs and 13 downregulated miRNAs. The elevated expression of miR-19b, miR-26a, miR-26b, and miR-29a in FFPE tumor tissue was further validated in both the cytoplasm and the nucleus using fluorescence in situ hybridization (FISH). Furthermore, the plasma expression levels of miR-19b and miR-29a in the mesothelioma group were significantly higher than those in any of the other four groups, and similar expression differences were found in miR-26a and miR-26b between the mesothelioma group and any other group except the LC group. Diagnostic value analysis indicated high sensitivity and specificity of these four miRNAs in distinguishing MM patients from PP patients, AE subjects, and healthy controls. Conclusively, miR-19b, miR-26a, miR-26b and miR-29a are potential blood biomarkers for the early or differential diagnosis of MM.}, } @article {pmid40407381, year = {2025}, author = {Kijima, T and Kato, T and Goto, Y and Kuribayashi, K and Mikami, K and Negi, Y and Murakami, S and Yoshida, T and Homma, M and Wakana, A and Noguchi, K and Fujimoto, N}, title = {KEYNOTE-A17: First-Line Pembrolizumab Plus Cisplatin-Pemetrexed in Japanese Participants With Advanced Pleural Mesothelioma.}, journal = {Cancer science}, volume = {}, number = {}, pages = {}, doi = {10.1111/cas.70082}, pmid = {40407381}, issn = {1349-7006}, support = {//Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA/ ; }, abstract = {Pleural mesothelioma (PM) is an inflammatory cancer linked with asbestos exposure and has a poor prognosis. We report results of the phase 1b KEYNOTE-A17 study (NCT04153565) of first-line pembrolizumab plus chemotherapy in Japanese participants with advanced PM. Participants aged ≥ 20 years with previously untreated, histologically confirmed advanced or unresectable PM received pembrolizumab 200 mg every 3 weeks (Q3W) for ≤ 35 cycles with cisplatin 75 mg/m[2] and pemetrexed 500 mg/m[2] Q3W for 4-6 cycles. Primary endpoints were the rate of dose-limiting toxicities (DLTs), adverse events (AEs), and treatment discontinuations due to AEs. DLTs were assessed during cycle 1 in 18 participants, and having ≤ 8 participants with DLTs was considered tolerable. AEs were graded per NCI CTCAE 5.0. Tumor response was evaluated per modified RECIST for PM by the investigator. Among 19 participants enrolled, the median study follow-up was 30.8 (range, 27.8-33.3) months (data cutoff September 21, 2022). Of 18 participants evaluated for DLTs, 2 (11%) experienced 4 DLTs (hypoalbuminemia, malaise, pyrexia in 1 participant; uveitis in 1 participant). 18/19 participants (95%) experienced treatment-related AEs; 14 (74%) had grade 3-4 events (no grade 5). Treatment-related AEs led to discontinuation of any drug in 5 participants (26%). The objective response rate was 74% (partial response, n = 14), and the median (range) duration of response was 16.8 (3.0-26.3+) months. First-line pembrolizumab plus chemotherapy was tolerable based on the low incidence of DLTs and showed acceptable safety and preliminary antitumor activity in Japanese participants with advanced PM. Trial Registration: NCT04153565.}, } @article {pmid40404863, year = {2025}, author = {Štěpánek, L and Nakládalová, M and Janošíková, M and Štěpánek, L and Boriková, A}, title = {Cumulative asbestos exposure as a key predictor of long-term pleuropulmonary outcomes: insights from decades of follow-up.}, journal = {International archives of occupational and environmental health}, volume = {}, number = {}, pages = {}, pmid = {40404863}, issn = {1432-1246}, abstract = {PURPOSE: Occupational asbestos exposure was widespread before regulatory bans, and it remains a risk during renovations or demolitions of older buildings. While asbestos-related diseases are well-documented, less is known about minor radiological changes in exposed individuals. This longitudinal study aimed to identify predictors of pleural and parenchymal lung disorders in individuals with previous occupational asbestos exposure, focusing on both established asbestos-related diseases and minor radiological abnormalities.

METHODS: The study tracked 445 former employees (334 men, 111 women) of two Czech asbestos-processing plants, who underwent regular examinations from the 1980s to December 2022. Cox proportional hazards regression models were employed to analyse predictors of asbestos-related diseases, as well as minor radiological findings alone.

RESULTS: Over a median latency of 37 years, 127 participants (28.5%) developed asbestos-related diseases, mainly pleural mesothelioma (59 cases). An additional 168 participants (37.8%) exhibited minor radiological findings, predominantly pleural plaques (129 cases), while 150 (33.7%) had no abnormalities. Substantial cumulative exposure was a strong predictor for minor radiological findings (odds ratio [OR] 1.98, 95% confidence interval [CI] 1.18-3.35, p = 0.010) and any endpoint, including diseases (OR 1.89, 95% CI 1.18-3.02, p = 0.008). Respiratory symptoms and impaired spirometry results significantly increased the likelihood of endpoint occurrence. No significant differences emerged between settings with predominantly chrysotile exposure and those with a chrysotile-crocidolite mixture.

CONCLUSION: This study highlights the predictive value of cumulative exposure and the need for ongoing surveillance of occupationally exposed individuals to better understand radiological changes, their significance, and to refine risk assessment models.}, } @article {pmid40398085, year = {2025}, author = {Rosati, D and Maurizi, BG and Serio, VB and Maffeo, D and Rina, A and Mari, F and Palmieri, M and Giordano, A and Frullanti, E}, title = {From asbestos exposure to carcinogenesis: Transcriptomic signatures in malignant pleural mesothelioma.}, journal = {Experimental and molecular pathology}, volume = {143}, number = {}, pages = {104973}, doi = {10.1016/j.yexmp.2025.104973}, pmid = {40398085}, issn = {1096-0945}, abstract = {BACKGROUND: The incidence of malignant pleural mesothelioma (MPM) has surged due to widespread asbestos exposure, particularly since the mid-20th century. Despite significant advancements in cancer treatment, an effective cure for MPM remains elusive, largely due to a limited understanding of the molecular mechanisms underlying asbestos-related carcinogenesis. This exploratory study aims to uncover gene expression patterns uniquely altered in mesothelioma patients with documented asbestos exposure, providing a solid foundation for future research focused on identifying novel prognostic and predictive biomarkers.

METHODS: Publicly available RNA sequencing data were analyzed through a bioinformatics pipeline to perform differential gene expression analysis. Additionally, functional enrichment analysis was applied to highlight significantly enriched Gene Ontology (GO) terms related to biological processes, molecular functions, and cellular components, offering insights into the molecular pathways involved in MPM development.

RESULTS: The analysis uncovered a set of differentially expressed genes (DEGs) in MPM patients with documented asbestos exposure, as well as key GO terms. These enriched biological terms reflect processes such as ion homeostasis and oxidative stress response, providing crucial information on the cellular alterations driven by asbestos exposure.

CONCLUSION: This study's findings deepen our understanding of the molecular landscape underlying asbestos-induced carcinogenesis in MPM. The identification of specific DEGs and enriched GO terms lays the foundation for future investigations, including the development of biomarkers, with potential implications for the diagnostic and prognostic assessment of MPM.}, } @article {pmid40389217, year = {2025}, author = {Franckenberg, S and Theissen-Lauk, O and Frauenfelder, T}, title = {[Modern Radiological Approaches to the Diagnosis and Staging of Pleural Mesothelioma].}, journal = {Zentralblatt fur Chirurgie}, volume = {}, number = {}, pages = {}, doi = {10.1055/a-2576-6585}, pmid = {40389217}, issn = {1438-9592}, abstract = {Pleural mesothelioma (PM) is a highly aggressive tumour, mainly associated with prior asbestos exposure. Symptoms typically do not manifest until 20 to 50 years after exposure. Depending on the histological subtype of PM, the prognosis varies, though the median survival time is only 12-18 months. Imaging plays a central role in the management of PM patients, particularly in assessing operability and treatment response. However, PM presents a unique challenge for radiology due to its rarity, complex morphology, and tendency to invade multiple tissue layers simultaneously. Contrast-enhanced computed tomography (CT) is the central imaging modality in the diagnosis, preoperative planning and therapy monitoring of pleural mesothelioma (PM). Ideally, CT should include both the thorax and abdomen to capture the entire pleural space. Tumour thickness and volume, as determined by CT, are important prognostic factors for patient survival in PM. In addition, PET/CT, using radioactively labelled fluorodeoxyglucose ([18]F-FDG), offers additional valuable insights into tumour metabolism. Since PM is typically metabolically active, PET/CT is particularly effective in detecting smaller lesions, occult metastases, and assessing morphologically ambiguous lesions. Magnetic resonance imaging (MRI), on the other hand, offers distinct advantages over CT, due to its superior soft tissue contrast, particularly in visualizing tumour extent and infiltration of adjacent structures. Dynamic contrast-enhanced imaging, diffusion-weighted imaging, and 4D sequences provide valuable additional information. On the basis of the "Best Practices" of the expert panel from the International Mesothelioma Interest Group (iMig), we provide an overview of the common imaging modalities, including conventional X-ray, CT, MRI, and PET/CT. Additionally, we discuss staging based on the TNM classification (Tumour, Node, Metastasis), which evaluates the local invasion of the tumour (T), lymph node involvement (N), and the presence of metastases (M). We also present examples of assessing treatment response and highlight recent developments in diagnostic imaging.}, } @article {pmid40362314, year = {2025}, author = {Ashley, CN and Broni, E and Pena-Martinez, M and Wood, CM and Kwofie, SK and Miller, WA}, title = {Computer-Aided Discovery of Natural Compounds Targeting the ADAR2 dsRBD2-RNA Interface and Computational Modeling of Full-Length ADAR2 Protein Structure.}, journal = {International journal of molecular sciences}, volume = {26}, number = {9}, pages = {}, pmid = {40362314}, issn = {1422-0067}, support = {1912104//U.S. National Science Foundation/ ; 2216567//U.S. National Science Foundation/ ; }, mesh = {*Adenosine Deaminase/chemistry/metabolism ; *RNA-Binding Proteins/chemistry/metabolism/antagonists & inhibitors ; Humans ; Molecular Dynamics Simulation ; Molecular Docking Simulation ; Protein Binding ; *RNA, Double-Stranded/metabolism/chemistry ; Ligands ; *Biological Products/pharmacology/chemistry ; Drug Discovery ; Binding Sites ; }, abstract = {Mesothelioma is a rare and aggressive cancer linked to asbestos exposure and characterized by rapid metastasis and poor prognosis. Inhibition of adenosine deaminase acting on dsRNA 2 (ADAR2) RNA binding but not ADAR2 editing has shown antitumor effects in mesothelioma. Natural compounds from the Traditional Chinese Medicine (TCM) database were docked to the RNA-binding interface of ADAR2's second dsRNA binding domain (dsRBD2), and their drug-likeness and predicted safety were assessed. Eight ligands (ZINC000085597263, ZINC000085633079, ZINC000014649947, ZINC000034512861, ZINC000070454124, ZINC000085594944, ZINC000085633008, and ZINC000095909822) showed high binding affinity to dsRBD2 from molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) calculations. Protein-ligand interactions were analyzed to identify key residues contributing to these binding affinities. Molecular dynamics (MD) simulations of dsRBD-ligand-RNA complexes revealed that four compounds (ZINC000085597263, ZINC000085633079, ZINC000014649947, and ZINC000034512861) had negative binding affinities to dsRBD2 in the presence of the RNA substrate GluR-2. Key residues, including Val164, Met165, Lys209, and Lys212, were crucial for ligand binding, even with RNA present, suggesting these compounds could inhibit dsRBD2's RNA-binding function. The predicted biological activities of these compounds indicate potential anticancer properties, particularly for the treatment of mesothelioma. These compounds are structurally similar to known anti-mesothelioma agents or anticancer drugs, highlighting their therapeutic potential. Current mesothelioma treatments are limited. Optimization of these compounds, alone or in combination with current therapeutics, has potential for mesothelioma treatment. Additionally, five high-quality full-length ADAR2 models were developed. These models provide insights into ADAR2 function, mutation impacts, and potential areas for protein engineering to enhance stability, RNA-binding specificity, or protein interactions, particularly concerning dimerization or complex formation with other proteins and RNAs.}, } @article {pmid40361508, year = {2025}, author = {Cedres, S and Valdivia, A and Priano, I and Rocha, P and Iranzo, P and Pardo, N and Martinez-Marti, A and Felip, E}, title = {BAP1 Mutations and Pleural Mesothelioma: Genetic Insights, Clinical Implications, and Therapeutic Perspectives.}, journal = {Cancers}, volume = {17}, number = {9}, pages = {}, doi = {10.3390/cancers17091581}, pmid = {40361508}, issn = {2072-6694}, abstract = {Pleural mesothelioma (PM) is a locally aggressive tumor associated with asbestos exposure. Despite legislative efforts to regulate asbestos use, its incidence continues to rise in some parts of the world. Chemotherapy and immunotherapy have improved survival in PM patients, but overall survival remains poor. Molecular analysis of PM patients has shown that most alterations occur in tumor suppressor genes, with BAP1 being the most frequently affected. Patients with germline BAP1 mutations have been reported to have a better prognosis, but this is not observed in those with somatic mutations. Interest in developing drugs targeting patients with BAP1 loss has led to several phase II studies in recent years. Unfortunately, initial results have not been very promising. In this review, we conclude that, at this time, with the contradictory results from studies and the limited number of patients evaluated, BAP1, the most commonly altered gene in PM, is not yet suitable for use in clinical practice as a prognostic or predictive factor. Future studies are needed to establish the prognostic or predictive value of BAP1.}, } @article {pmid40355086, year = {2025}, author = {Horie, M and Sugino, S and Fujita, K and Endoh, S and Maru, J and Matsuzawa, T and Ogura, I}, title = {Evaluation of inflammatory and mesothelioma-related responses in mice following the intraperitoneal administration of cellulose nanofibers.}, journal = {NanoImpact}, volume = {}, number = {}, pages = {100561}, doi = {10.1016/j.impact.2025.100561}, pmid = {40355086}, issn = {2452-0748}, abstract = {Mesothelioma can develop from long-term exposure to fine fibrous materials including asbestos and carbon nanotubes, and chronic inflammation is critical for its development. Inflammatory responses and key related markers associated with the development of mesothelioma were evaluated over time in relation to cellulose nanofibers (CNFs), which are being developed as new plant-derived materials, for the purpose of risk management Three types of CNFs, mechanically fibrillated CNFs, TEMPO-oxidized CNFs, and phosphorylated CNFs, were administered intraperitoneally to mice at doses of 0.1 and 1.0 mg per animal, and progress was observed for up to 2 years. In the group receiving mechanically fibrillated CNFs, white substances were observed adhering to the liver surface throughout the observation period. This white substance was presumed to be cellulose. Some CNFs have been shown to persist in the body. During this period, inflammation markers and mesothelioma-related markers were evaluated at 1, 2, and 6 months, and 1, and 2 years after administration. No significant symptoms were observed in animals administered one of the three types of CNFs intraperitoneally during the observation period. Inflammatory markers in the peritoneal lavage fluid remained below the detection limit throughout the entire observation period. Additionally, no significant increase in blood levels of mesothelioma or the major related markers mesothelin, osteopontin, or HMGB1 was observed. In this study, although some CNFs remained in the body, no inflammatory response was observed in vivo under the concentration conditions and observation periods used. Furthermore, no evidence of long-term effects, such as cancer, was found.}, } @article {pmid40340549, year = {2025}, author = {Ram, M and Afrash, MR and Moulaei, K and Esmaeeli, E and Khorashadizadeh, MS and Garavand, A and Amiri, P and Sabahi, A}, title = {Predicting Mesothelioma Using Artificial Intelligence: A Scoping Review of Common Models and Applications.}, journal = {Technology in cancer research & treatment}, volume = {24}, number = {}, pages = {15330338251341053}, pmid = {40340549}, issn = {1533-0338}, mesh = {Humans ; *Artificial Intelligence ; Prognosis ; *Mesothelioma/diagnosis/etiology ; *Mesothelioma, Malignant/diagnosis ; Neural Networks, Computer ; Bayes Theorem ; }, abstract = {IntroductionMesothelioma is a type of lung cancer caused by asbestos exposure, and early diagnosis is crucial for improving survival chances. Artificial intelligence offers a potential solution for the timely diagnosis and staging of the disease. This study aims to review the latest research conducted in artificial intelligence applications to predict mesothelioma.MethodsUntil April 24, 2023, PubMed, Scopus, and Web of Science databases were searched comprehensively for articles on artificial intelligence in mesothelioma management. The data was gathered using a standardized extraction form, and the findings were reported in figures and tables.ResultsOne hundred and seventy-three articles were identified from database searches, which were then reduced to 151 after eliminating duplicates. Finally, 19 articles were selected for inclusion in our study. The applications of artificial intelligence in these articles primarily focused on tumor diagnosis and classification (73.69%), followed by prevention and prognosis (21.05%) and tumor volumetric measurement of malignant pleural mesothelioma (5.26%). The most frequently used AI models include types of neural networks (NN), decision trees (DT), random forests (RF), logistic regression (LogR), Naïve Bayes (NB), and support vector machines (SVM). SVM, DT, and RF emerged as prominent models, achieving high accuracies ranging from 78.3% to 99.97%. Genetic algorithms, correlation-based algorithms, and Neural Networks were employed for risk factor identification and feature selection.ConclusionArtificial intelligence, particularly machine learning models such as neural networks, decision trees, support vector machines, and random forests, holds promise in predicting and managing mesothelioma, potentially enhancing early detection and improving patient outcomes.}, } @article {pmid40338466, year = {2025}, author = {Bonsignore, G and Ranzato, E and Martinotti, S}, title = {Unraveling BOLD-100 synergistic potential in pleural mesothelioma treatment: an in vitro study.}, journal = {Investigational new drugs}, volume = {}, number = {}, pages = {}, pmid = {40338466}, issn = {1573-0646}, abstract = {Pleural mesothelioma (PM) is a rare cancer affecting the pleural layer on the body's serosal surfaces. Exposure to asbestos fibers, a naturally occurring fibrous material with insulating characteristics, contributes to PM's prevalence. PM has a long latency period, making major surgery ineffective and necessitating systemic treatment. Despite the progress of mesothelioma treatment, the median survival is very poor; so, there is a strong need to explore new therapeutic approaches. This study explores the use of BOLD-100, a novel therapeutic drug that targets GRP78, a protein overexpressed in PM cells. BOLD-100, a ruthenium-based small molecule therapeutic drug, is being investigated for the treatment of advanced gastrointestinal malignancies in conjunction with chemotherapy. Our aim is to investigate cellular responses of several PM cell lines to a regimen that includes BOLD-100 in addition to other commonly used treatments. BOLD-100 is a ruthenium-based anticancer therapeutic.}, } @article {pmid40330553, year = {2025}, author = {Wylie, AG and Korchevskiy, AA}, title = {Critical values for dimensional parameters of mesotheliomagenic mineral fibers: evidence from the dimensions and rigidity of MWCNT.}, journal = {Frontiers in toxicology}, volume = {7}, number = {}, pages = {1568513}, pmid = {40330553}, issn = {2673-3080}, abstract = {MWCNT (multi-walled carbon nanotubes) used in 72 animal instillation or inhalation studies were classified by average length, average width, Young's modulus, Rigidity Index (RI), and potency for mesothelioma in animals. The RI is based on the Euler buckling theory. MWCNT that induce mesothelioma have average lengths >2 µm and widths >37 nm, and average RI > 0.05 (µm[2] x GPa x 10[4]). Many noncarcinogenic MWCNT materials have RI < 0.05 and lack biological rigidity. In comparison, Elongate Mineral Particle (EMP) populations with one exception have RI > 0.05. Mineral particles likely to have RI < 0.05 include chrysotile fibrils with lengths >5 μm, amosite and crocidolite fibers with widths <60 nm, and sheet silicate fibers with widths <200 nm. The product of percent EMPA, average RI, and biosolubility among silicates correlates with known mesothelioma potency. The derived models reproduce published values of RM with high statistical significance (P < 0.05). Average RI, length, and width are critical parameters for mesotheliomagenicity for both MWCNT and EMPA mineral fiber.}, } @article {pmid40327427, year = {2025}, author = {Nawojowska, A and Mendes, S and Gaspar, M and Cabral, D and Rodrigues, C and Antunes, M and Alvoeiro, M and Calado, T and Félix, F}, title = {Oncological Outcomes Of Radical Surgery With And Without Induction And Adjuvant Chemotherapy In Mesothelioma Patients - 8-Year Experience In A Single Center.}, journal = {Portuguese journal of cardiac thoracic and vascular surgery}, volume = {32}, number = {1}, pages = {35-40}, doi = {10.48729/pjctvs.457}, pmid = {40327427}, issn = {2184-9927}, mesh = {Humans ; Chemotherapy, Adjuvant ; Male ; Middle Aged ; Aged ; Female ; *Mesothelioma/mortality/therapy/surgery/drug therapy ; Neoadjuvant Therapy ; Disease-Free Survival ; Treatment Outcome ; Induction Chemotherapy ; Retrospective Studies ; Time Factors ; *Lung Neoplasms/mortality/therapy ; *Pleural Neoplasms/mortality/therapy ; Adult ; }, abstract = {INTRODUCTION: Mesothelioma is a devastating, insidious disease with a long latency period. Its peak incidence occurs in the 5th and 6th decades of life, up to 40 years after asbestos exposure which is strongly related to the disease. The optimal treatment is the object of an intense discussion.

AIMS: The established outcomes were disease-free survival (DFS) and 1-year survival analyzed in the context of neoadjuvant chemotherapy with subsequent surgery, surgical intervention without any systemic treatment, an upfront surgery and adjuvant chemotherapy and surgical intervention with both neo- and adjuvant therapy to establish the most advantageous treatment in terms of oncological results.

MATERIALS AND METHODS: We analyzed our center's surgical experience with radical surgery for mesothelioma, evaluating the disease-free time and 1-year survival in relation to the treatment scheme. A search of the department's surgical database for mesothelioma cases between January 2016 and December 2020 revealed 16 cases, which were included in the final analysis. The established outcomes were disease-free survival and 1-year survival.

RESULTS: The 3 patients treated with surgery without any systemic treatment had a median follow-up period (MFUP) of 7 months (3- 12), 67% of recurrence, DFS of 6 months (0-12), and 1-year survival of 33%. The 6 patients treated with neoadjuvant chemotherapy, surgical resection, and adjuvant therapy, had an MFUP of 45 months (8-82), 67% of recurrence, DFS of 32 months (2-82), and 1-year survival of 83%. The 1 patient, treated with neoadjuvant chemotherapy and subsequently, surgery had a follow-up of 29 months with DFS of 20 months and he was alive at the time of submission of this article. The 6 patients treated with an up-front surgery and adjuvant chemotherapy had an MFUP of 20 months (8-33), 67% of recurrence, DFS of 15 months (6-33), and 1-year survival of 67%.

CONCLUSION: Despite the limitations of the study, the multimodal approach with both neoadjuvant and adjuvant chemotherapy demonstrated the longest MFUP, DFS, and 1-year survival. The worst results were observed in patients treated only with radical surgery, while the sequence of systemic treatment did not influence the rate of recurrence.}, } @article {pmid40326864, year = {2025}, author = {Christensen, HS and Jensen, RH and Nielsen, LH and Bertelsen, LD and Teglgaard, C and Bønløkke, JH and Severinsen, MT and Bøgsted, M}, title = {Detailed mapping of mesothelioma cases in Denmark to identify areas with elevated risk: a nationwide population-based study.}, journal = {Scandinavian journal of work, environment & health}, volume = {}, number = {}, pages = {}, doi = {10.5271/sjweh.4229}, pmid = {40326864}, issn = {1795-990X}, abstract = {OBJECTIVES: Previous studies mapping pleural mesothelioma in Denmark have found that the risk varies between Danish regions. However, evaluating disease risk for such relatively large geographical units ignores any heterogeneity within the unit and can thus diminish more local spikes in risk, missing smaller areas of excess risk. In this study, we examined the distribution of pleural mesothelioma in Denmark on an unprecedented detailed scale, mapping cases to each of the Danish parishes.

METHODS: We identified individuals diagnosed with pleural mesothelioma between 1990 and 2021 in the Danish Cancer Registry. Considering age- and sex-standardized incidence rate ratios (IRR), we used a conditional autoregressive random effects model to smooth IRR across parishes. Parishes with a smoothed parish-to-national IRR >1.25 or >2.0 with a posterior probability of >95% were flagged as parishes with an excess risk of pleural mesothelioma.

RESULTS: We identified 3105 incident cases of pleural mesothelioma in the study period. A total of 74 and 14 parishes were flagged with IRR significantly above 1.25 and 2.0, respectively. These parishes had posterior mean smoothed IRR of 1.82-4.13.

CONCLUSIONS: We provided a detailed mapping of pleural mesothelioma cases in Denmark and found five distinct areas, each covering several parishes, with a significantly elevated risk. All these areas were in the proximity of previous asbestos-using industries.}, } @article {pmid40282929, year = {2025}, author = {Kalkan, Z and Ebinc, S and Arcagok, M and Bilici, A and Yildiz, O and Kilickap, S and Guven, DC and Tatli, AM and Sumbul, AT and Mandel, NM and Ozturk, A and Bardakci, M and Karakaya, S and Kaplan, MA}, title = {Efficacy of Immunotherapy Versus Chemotherapy in Advanced Pleural Mesothelioma: A Turkish Oncology Group (TOG) Study.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {61}, number = {4}, pages = {}, pmid = {40282929}, issn = {1648-9144}, mesh = {Humans ; Male ; Female ; Middle Aged ; Retrospective Studies ; *Immunotherapy/methods/standards ; Turkey ; Aged ; *Pleural Neoplasms/drug therapy ; *Mesothelioma/drug therapy/therapy ; Adult ; Mesothelioma, Malignant ; Treatment Outcome ; Progression-Free Survival ; }, abstract = {Background and Objectives: This study aimed to evaluate the effectiveness of immunotherapy compared to chemotherapy across different treatment lines in patients with pleural mesothelioma. It also sought to identify factors influencing the success of immunotherapy, such as histological subtype, PD-L1 expression, type of asbestos exposure, and metastatic status. Materials and Methods: A retrospective analysis was conducted with 60 patients diagnosed with pleural mesothelioma. Data on age, gender, histological subtype, and asbestos exposure were collected for all patients and PD-L1 expression was assessed in a subset of patients. Patients received either chemotherapy or immunotherapy as first-, second-, and third-line treatments, and progression-free survival (PFS) and treatment responses were evaluated. Results: Among the 60 patients, 35 (58.3%) were male and the median age was 59 years. The majority (71.7%) had epithelioid histology and 28.3% had distant metastases. Asbestos exposure was documented in 65% of the cases. PD-L1 expression of ≥1% was found in 13 of 17 patients tested. First-line treatments included immunotherapy for 11 patients and chemotherapy for the others, with immunotherapy achieving median PFS of 9 months versus 6 months for chemotherapy, although the difference was not statistically significant. In third-line treatments, immunotherapy significantly outperformed chemotherapy with median PFS of 6 months compared to 3 months (p = 0.048). Absence of metastasis and prior asbestos exposure in an endemic region were linked to better immunotherapy outcomes. Conclusion: Immunotherapy shows increased efficacy in later treatment lines for pleural mesothelioma, especially for patients without metastases or with prior endemic asbestos exposure. Tailored therapeutic strategies should be further explored in prospective studies.}, } @article {pmid40277909, year = {2025}, author = {Magouliotis, DE and Minervini, F and Cioffi, U and De Simone, M and Patrini, D and Scarci, M}, title = {The Role of Epithelial-Mesenchymal Transition in Malignant Pleural Mesothelioma: From Pathogenesis to Diagnosis and Treatment.}, journal = {Cells}, volume = {14}, number = {8}, pages = {}, pmid = {40277909}, issn = {2073-4409}, mesh = {Humans ; *Epithelial-Mesenchymal Transition ; *Mesothelioma, Malignant/diagnosis/therapy/pathology ; *Pleural Neoplasms/diagnosis/therapy/pathology ; Signal Transduction ; Biomarkers, Tumor/metabolism ; Animals ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive cancer of the pleural lining, primarily associated with asbestos exposure. Despite advancements in multimodal treatment, patient survival remains poor. Epithelial-mesenchymal transition (EMT) has emerged as a crucial process driving MPM pathogenesis, metastasis, and resistance to therapy. This review explores the molecular mechanisms underlying EMT in MPM, including key signaling pathways such as TGF-β, Wnt/β-catenin, and PI3K/Akt. We also discuss the diagnostic and prognostic significance of EMT-related biomarkers and emerging targeted therapies aimed at reversing EMT or exploiting EMT-induced vulnerabilities. Additionally, recent clinical trials, including the MARS 2 trial, are reviewed to provide insight into the evolving treatment landscape.}, } @article {pmid40248456, year = {2025}, author = {Didier, AJ and Li, M and Gheeya, J and Alahmadi, A and Kaufman, J and Memmott, R and He, K and Shields, P and Carbone, DP and Presley, C and Owen, D and Roof, L}, title = {Trends in Mesothelioma Mortality in the United States Between 1999 and 2020.}, journal = {JTO clinical and research reports}, volume = {6}, number = {5}, pages = {100804}, pmid = {40248456}, issn = {2666-3643}, abstract = {INTRODUCTION: Mesothelioma is a rare but aggressive cancer primarily caused by asbestos exposure. In March 2024, the Environmental Protection Agency banned asbestos in the United States, but its use will take years to phase out. Therefore, asbestos remains a threat, and incidence may remain stable or slowly decrease due to the long latency between exposure and diagnosis. This study investigates mesothelioma mortality trends in the United States from 1999 to 2020, focusing on demographic and geographic variations.

METHODS: Data on mesothelioma-related deaths from 1999 to 2020 were extracted from the Centers for Disease Control and Prevention database. Variables including race/ethnicity, sex, geographic density, and mesothelioma subtype were assessed. Age-adjusted mortality rates were calculated per 1 million individuals and standardized to the 2000 United States population. Joinpoint regression identified statistically significant changes in mortality trends over time.

RESULTS: From 1999 to 2020, there were 54,905 mesothelioma-related deaths in the United States (age-adjusted mortality rate = 7.5). Pleural mesothelioma accounted for 8.1% of deaths, peritoneal for 4.6%, pericardial for 0.01%, other sites for 10.9%, and unspecified sites for 76.3%. Most deaths (81.3%) occurred in individuals aged over 65 years. Overall mortality decreased from 8.5 in 1999 to 5.7 in 2020 at -1.9% annually. Non-Hispanic Whites had the highest mortality, and male individuals experienced higher mortality than female individuals. Suburban and rural populations had the highest mortality rates.

CONCLUSIONS: The study highlights significant declines in mesothelioma mortality in the United States from 1999 to 2020, with variations across demographic and geographic groups. Continued monitoring and targeted interventions are necessary to address disparities and further reduce mesothelioma mortality.}, } @article {pmid40239912, year = {2025}, author = {Lamote, K and Delanghe, S and Speeckaert, MM and van Meerbeeck, JP and Delanghe, JR}, title = {Haptoglobin phenotype: A germline risk factor for malignant pleural mesothelioma? A case-control study.}, journal = {Clinica chimica acta; international journal of clinical chemistry}, volume = {}, number = {}, pages = {120309}, doi = {10.1016/j.cca.2025.120309}, pmid = {40239912}, issn = {1873-3492}, abstract = {PURPOSE: The pathogenesis of malignant pleural mesothelioma (MPM) is linked to asbestos-induced chronic inflammation, oxidant formation, hemolysis and subsequent hemoglobin (Hb) release, potentiating oxidative injury. Haptoglobin (Hp) serves as a major antioxidant by binding free Hb in order to prevent its harmful effects. Dependent on the Hp-phenotype, this complexing can be divergent, leading to additional formation of reactive oxygen species (ROS) above those directly induced by asbestos or released by inflammatory cells. In order to determine the Hp-phenotype as a risk factor in MPM, this case-control study compared the Hp-phenotype distribution in MPM patients with asymptomatic persons with former occupational asbestos exposure (AEx) and controls from a European population.

MATERIALS AND METHODS: Hp-phenotyping was done on serum samples of 118 MPM patients and 96 AEx subjects by starch gel electrophoresis. The frequencies of Hp phenotypes (Hp 1-1, Hp 2-1 and Hp 2-2) and alleles (Hp[1], Hp[2]) were compared with those from 918 healthy control subjects.

RESULTS: The Hp 1-1 phenotype was overrepresented in MPM patients compared to AEx persons (P = 0.001) and healthy controls (P = 0.005). The relative risk for developing MPM when having the Hp 1-1 phenotype was 3.05 (1.47-6.34) for AEx subjects and 1.74 (1.19-2.54) for healthy controls compared to other phenotypes.

CONCLUSION: Our results indicate an important role of the Hp-phenotype in MPM pathogenesis suggesting that Hp 1-1 phenotypic persons are more prone for MPM development. Apart from the asbestos-induced radical formation, this finding confirms the role of oxidative stress in cancer development.}, } @article {pmid40236706, year = {2025}, author = {Revelant, A and Gessoni, F and Montico, M and Dhibi, R and Brisotto, G and Casarotto, M and Zanchetta, M and Paduano, V and Sperti, F and Evangelista, C and Giordari, F and De Re, V and Trovò, M and Minatel, E and Mascarin, M and Steffan, A and Muraro, E}, title = {Radical hemithorax radiotherapy induces an increase in circulating PD-1[+] T lymphocytes and in the soluble levels of PD-L1 in malignant pleural mesothelioma patients: a possible synergy with PD-1/PD-L1 targeting treatment?.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1534766}, pmid = {40236706}, issn = {1664-3224}, mesh = {Humans ; *Mesothelioma, Malignant/radiotherapy/immunology ; Male ; *Programmed Cell Death 1 Receptor/metabolism/immunology ; Middle Aged ; Aged ; Female ; *B7-H1 Antigen/blood/metabolism/immunology ; *Pleural Neoplasms/radiotherapy/immunology/blood ; *T-Lymphocytes/immunology/metabolism/radiation effects ; Aged, 80 and over ; }, abstract = {Malignant Pleural Mesothelioma (MPM) is an aggressive tumor associated with asbestos exposure, characterized by a poor prognosis, managed with surgery, chemotherapy and radiotherapy. Recently, immunotherapy gives a survival advantage compared to chemotherapy, but limited to the non-epithelioid histotype, the rarest type. Radical hemithorax radiotherapy (RHRT) improves the Overall Survival (OS) of MPM patients, irrespective of histotype, and is able to induce immunomodulatory effects. In this study we aim to investigate changes in circulating T lymphocytes phenotype and activity, in MPM patients undergoing RHRT, to evaluate a possible therapeutic space for immunotherapy in this setting. To assess immunomodulatory effects of RHRT we evaluate peripheral blood samples of 35 MPM patients collected before treatment, at the end of RT, and 1 month later. We first notice that higher Lymphocyte-to-Monocyte Ratio (LMR) levels, before RT, are associated with an improved OS. The immune monitoring performed by ELISA assays reveals a significant increase in the serum levels of soluble PD-L1 (sPD-L1) and IFN-γ at the end of RHRT. Furthermore, the percentage of PD-1[+] cells, evaluated by flow cytometry, significantly raise after RHRT in T cells, both CD4[+] and CD8[+]. Also the proportion of proliferative cells is significantly expanded after RHRT in all T cell subtypes. After treatment we observe a significant increase in the number of patients showing WT-1 specific CD4[+] T cells, measured by intracellular staining. The TCR repertoire analysis, investigated by Next Generation Sequencing, reveals an increased number of expanded T-cell clones after RHRT, and an association between TCR clonality and the percentage of proliferating cytotoxic T lymphocytes. The comparison of TCR sequences obtained in our cohort with those described in a literature cohort of MPM patients, reveals common entries, specific for MPM-associated antigens including WT-1. In this setting, pre-treatment levels of LMR seem to have a positive prognostic role, and RHRT would appear to induce immunomodulating effects, potential biomarkers for immunotherapy eligibility: i.e. increased PD-1[+] T lymphocytes, proliferating T cells, expanded T cell clones and augmented levels of sPD-L1. These data suggest the design of a prospective study evaluating a maintenance immunotherapy after RHRT in MPM, even in the epithelioid histotype.}, } @article {pmid40232704, year = {2025}, author = {Walker-Bone, K and Goodwin, MA and Bufton, B and Davis, BA and Wong, H and Harvey, J and Barker, S and Chalker, E and Klebe, S and Prabhakaran, S and Brims, FJ and MacFarlane, E and Benke, G and Mahoney, K and Driscoll, TR}, title = {Mesothelioma Incidence rates in Australia since 1982: exploring age, period and cohort effects and future projections.}, journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology}, volume = {}, number = {}, pages = {}, doi = {10.1158/1055-9965.EPI-24-1224}, pmid = {40232704}, issn = {1538-7755}, abstract = {Background Use of asbestos-containing products was banned in Australia in 2003. However, rates of new cases of mesothelioma, which has a very long latent period between exposure and disease, have continued to increase. The aim of this study was to investigate mesothelioma incidence in Australia by year of birth and age-period-cohort analysis and to develop projections of expected mesothelioma cases to 2034. Methods Data came from the Australian Cancer Database which provides complete national records of mesothelioma cases notified 1982-2020. Incidence rates were age-standardised to the 2001 Australian Standard Population to enable comparisons of the population across time. Age-period-cohort models were used to examine the temporal trends of incidence rates by age, calendar year and birth cohort. Projections for incidence rates of mesothelioma 2020-34 were estimated using Nordpred models. Results Graphs of age-standardised incidence rates of mesothelioma suggest a birth cohort effect and the age-period-cohort model confirmed this. There was a birth cohort effect in all cohorts born before 1960, strongest in cohorts born 1920-1949. Projection modelling to 2034 suggested that the age-standardised rates will continue to decline while crude incidence rates of mesothelioma will stabilise and then gradually decline, mostly among people aged 60-84 years. Conclusions The findings are consistent with the greatest risk of mesothelioma in Australia occurring in cohorts with the highest levels of historical cumulative occupational exposure, showing the value of a ban on asbestos. Impact The number of new cases of mesothelioma per year is not expected to decline until after 2030.}, } @article {pmid40227645, year = {2025}, author = {Bertuccio, FR and Montini, S and Fusco, MA and Di Gennaro, A and Sciandrone, G and Agustoni, F and Galli, G and Bortolotto, C and Saddi, J and Baietto, G and Melloni, G and D'Ambrosio, G and Corsico, AG and Stella, GM}, title = {Malignant Pleural Mesothelioma: From Pathophysiology to Innovative Actionable Targets.}, journal = {Cancers}, volume = {17}, number = {7}, pages = {}, doi = {10.3390/cancers17071160}, pmid = {40227645}, issn = {2072-6694}, abstract = {BACKGROUND: Pleural mesothelioma (PM) is a rare and highly aggressive cancer which arises from mesothelial layer and primarily linked to asbestos exposure, genetic predispositions, and specific mutations. Despite current treatment modalities, including chemotherapy, antiangiogenic therapy and more recently immunotherapy, the prognosis remains dismal, with a median survival time of 6-18 months.

OBJECTIVES: The urgent need for novel therapeutic strategies has prompted research into molecular targets and precision medicine approaches. At present, many potential targets for therapeutic strategies have been identified, and emerging clinical trials are demonstrating certain clinical efficacy.

METHODS: This review examines advancements in understanding PM's genetic and epigenetic landscape, signaling pathways, and promising therapeutic targets.

RESULTS: We also discuss the results of recent clinical trials and their potential implications for future treatment paradigms.}, } @article {pmid40223054, year = {2025}, author = {Li, J and Wang, X and Lin, Y and Li, Z and Xiong, W}, title = {Integrative eQTL and Mendelian randomization analysis reveals key genetic markers in mesothelioma.}, journal = {Respiratory research}, volume = {26}, number = {1}, pages = {140}, pmid = {40223054}, issn = {1465-993X}, support = {Nos. 32160167 and 82160516//the National Natural Science Foundation of China/ ; Nos. 202201AT070004 and 202301AT070023//Yunnan Provincial Applied Basic Research Program General Project/ ; No. 202001BB0500080//Key Program of Yunnan Provincial Applied Basic Research Program/ ; }, mesh = {Humans ; *Mendelian Randomization Analysis/methods ; *Quantitative Trait Loci/genetics ; Genome-Wide Association Study/methods ; *Mesothelioma/genetics/diagnosis ; *Biomarkers, Tumor/genetics ; Genetic Markers/genetics ; Databases, Genetic ; Genetic Predisposition to Disease ; }, abstract = {BACKGROUND: Mesothelioma is a rare cancer that originates from the pleura and peritoneum, with its incidence increasing due to asbestos exposure. Patients are frequently diagnosed at advanced stages, resulting in poor survival rates. Therefore, the identification of molecular markers for early detection and diagnosis is essential.

METHODS: Three mesothelioma datasets were downloaded from the GEO database for differential gene expression analysis. Instrumental variables (IVs) were identified based on expression quantitative trait locus (eQTL) data for Mendelian randomization (MR) analysis using mesothelioma Genome-Wide Association Study (GWAS) data from the FINNGEN database. The intersecting genes from MR-identified risk genes and differentially expressed genes were identified as key co-expressed genes for mesothelioma. Functional enrichment analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA), as well as immune cell correlation analysis, were performed to elucidate the roles of key genes in mesothelioma. Additionally, the differential expression of key genes in mesothelioma was validated in independent GEO datasets and TCGA datasets. This integrative research combining multiple databases and analytical methods established a robust model for identifying mesothelioma risk genes.

RESULTS: The research conducted in our study identified 1608 genes that were expressed differentially in mesothelioma GEO datasets. By combining these genes with 192 genes from MR analysis, we identified 14 key genes. Notably, MPZL1, SOAT1, TACC3, and CYBRD1 are linked to a high risk of mesothelioma, while TGFBR3, NDRG2, EPAS1, CPA3, MNDA, PRKCD, MTUS1, ALOX15, LRRN3, and ITGAM are associated with a lower risk. These genes were found to be enriched in pathways associated with superoxide metabolism, cell cycle regulation, and proteasome function, all of which are linked to the development of mesothelioma. Noteworthy observations included a significant infiltration of M1 macrophages and CD4 + T cells in mesothelioma, with genes SOAT1, MNDA, and ITGAM showing a positive correlation with the level of M1 macrophage infiltration. Furthermore, the differential expression analyses conducted on the GEO validation set and TCGA data confirmed the significance of the identified key genes.

CONCLUSION: This integrative eQTL and Mendelian randomization analysis provides evidence of a positive causal association between 14 key co-expressed genes and mesothelioma genetically. These disease critical genes are implicated in correlations with biological processes and infiltrated immune cells related to mesothelioma. Moreover, our study lays a theoretical foundation for further research into the mechanisms of mesothelioma and potential clinical applications.}, } @article {pmid40215614, year = {2025}, author = {Jin, W and Ding, Z and Zhang, M and Shen, L and Wang, H and Huang, J and Xuzhang, W and Huang, Y and Dong, C and Li, C and Jiang, L and Yuan, Z and Ye, X}, title = {The global burden of mesothelioma and its association with asbestos bans, 1990-2021: a population-based study.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {203}, number = {}, pages = {108534}, doi = {10.1016/j.lungcan.2025.108534}, pmid = {40215614}, issn = {1872-8332}, abstract = {BACKGROUND: Mesothelioma, as a lethal consequence of asbestos exposure, poses a significant threat to high-risk populations. The Global Burden of Disease (GBD) 2021 update provides an opportunity to examine current mesothelioma epidemiology and assess whether asbestos bans have effectively reduced mesothelioma incidence over a longer time span than covered in existing literature.

METHODS: Annual cases and age-standardized rates (ASRs, reported per 100,000 person-years) of incidence, death, disability-adjusted life-years, and probability of death associated with mesothelioma among different age groups were obtained from patients in 204 countries and territories diagnosed with mesothelioma between 1990 and 2021. Estimated annual percentage changes (EAPCs) and period analysis of ASRs were employed to evaluate temporal trends in incidence and mortality. Data on global asbestos consumption and bans were collected from various sources to investigate their relationship with mesothelioma burdens.

RESULTS: In 2021, global incident cases of mesothelioma slightly increased to 31,908 [29,643, 34,115], with 23,184 [21,553, 24,941] in males and 8,724 [7,784, 9,580] in females, up from 31,173 [28,821, 33,090] in 2019, and approximately double the number in 1990 (16,493 [15,325, 17,783]). Australasia, Western Europe, and Southern Sub-Saharan Africa ranked in the top three for all ASRs. The United Kingdom and Australia had the highest ASRs globally, while the Northern Mariana Islands, El Salvador, Syrian Arab Republic, Iran (Islamic Republic of), Saudi Arabia, and Palestine had the lowest ASRs in 2021. Most countries with asbestos bans continued to exhibit declining trends in ASRs from 2019 to 2021.

CONCLUSIONS: Global asbestos bans have demonstrated sustained effectiveness in controlling mesothelioma. Accelerated implementation of asbestos bans in developing nations coupled with deeper exploration of mesothelioma pathogenesis would aid in enhancing primary prevention efforts. Although the mesothelioma burden is more severe in high-income regions, ASRs have decreased more notably in high and upper-middle socio-demographic indexes (SDIs) tiers with generally more comprehensive and earlier asbestos bans compared to other locations. The burden of female mesothelioma has shown slower remission compared to males in many regions recently, underscoring the importance of non-occupational exposures.}, } @article {pmid40213175, year = {2025}, author = {Ghiasvand, M and Fooladi Sarabi, S and Salehi, A and Seyedi Asl, FS and AlJasem, M and Yaghoubi, M and Ehsani Zunuz, B and Sanatian, Z and Alaghi, P and Khadembashiri, MA}, title = {Burden of mesothelioma in the Middle East and North Africa: a 32-year analysis of the Global Burden of Diseases Study 2021.}, journal = {Annals of medicine and surgery (2012)}, volume = {87}, number = {3}, pages = {1127-1139}, pmid = {40213175}, issn = {2049-0801}, abstract = {BACKGROUND: Mesothelioma, a cancer primarily caused by asbestos exposure, has been increasing in the Middle East and North Africa (MENA), raising concerns about the region's occupational and environmental health landscape. With varying Sociodemographic Index (SDI) and differing asbestos regulations across MENA, understanding mesothelioma trends over time is crucial.

METHODS: Using data from the Global Burden of Disease (GBD) Study 2021, we analyzed mesothelioma incidence, mortality, and disability-adjusted life years (DALYs) in MENA from 1990 to 2021. Age-standardized incidence rate (ASIR), mortality rate (ASMR), and disability rate (ASDR) were assessed by age, sex, and country. Trend analyses were conducted using joinpoint regression to identify significant shifts in disease burden over the study period.

RESULTS: Between 1990 and 2021, mesothelioma cases rose from 597 to 1365, with ASIR declining at an average annual percent change (AAPC) of -0.49% (P < 0.001). Countries like Oman and Saudi Arabia exhibited rising burdens, while the United Arab Emirates and Turkey saw declines. Males and older age groups had higher ASIR, ASMR, and ASDR rates, indicating gender- and age-based disparities.

CONCLUSION: While the mesothelioma burden in MENA has declined overall, significant increases in certain countries highlight the need for uniform asbestos regulations and targeted health interventions, especially among high-risk demographics. Further research on occupational exposure and Sociodemographic Index (SDI) improvements could help reduce mesothelioma rates across the region.}, } @article {pmid40188356, year = {2025}, author = {Javed, H and Ahmad, A and Rehman, A and Wagner, M and McKnight, JE}, title = {Delayed Diagnosis of Peritoneal Mesothelioma in Recurrent Ascites: A Case Report.}, journal = {The American journal of case reports}, volume = {26}, number = {}, pages = {e946777}, doi = {10.12659/AJCR.946777}, pmid = {40188356}, issn = {1941-5923}, mesh = {Humans ; Male ; *Peritoneal Neoplasms/diagnosis/complications ; Aged ; *Ascites/etiology ; *Mesothelioma/diagnosis/complications ; *Delayed Diagnosis ; Mesothelioma, Malignant ; Recurrence ; Tomography, X-Ray Computed ; *Lung Neoplasms/diagnosis ; }, abstract = {BACKGROUND Ascites is a common clinical sign noted in 3% to 4% of hospitalized medical patients. Nearly 94% of patients with ascites have non-malignant etiologies, with the most common being chronic liver disease. Peritoneal mesothelioma is an exceedingly rare malignancy associated with asbestos exposure. Here, we report the case of an elderly man who presented with recurrent loculated ascites and received a diagnosis of peritoneal mesothelioma after a delay of approximately 10 weeks. CASE REPORT A 67-year-old man with a history of asbestos exposure presented with abdominal distension and muscle wasting for 1 month. Initial abdominal CT was notable for smooth liver contour and massive ascites. Ascitic fluid analysis was consistent with low serum albumin-ascites gradient but showed negative cytology for malignant cells. Upper and lower endoscopies did not reveal lesions. Due to recurring ascites, serial abdominal paracenteses were performed, although cytology was negative for malignant cells. Repeat abdominal CT performed after 6 weeks showed worsening loculated ascites, with possible peritoneal carcinomatosis. At this point, percutaneous omental biopsy was performed, which established the diagnosis of peritoneal mesothelioma (75 days after initial presentation). CONCLUSIONS In patients presenting with recurrent ascites and a history of asbestos exposure, it is important to consider the diagnosis of peritoneal mesothelioma. While 94% of patients with ascites have non-malignant etiologies, a small proportion of patients can have malignant ascites. In patients in which the first set of ascitic fluid studies are inconclusive, repeat abdominal paracentesis and omental biopsy or diagnostic laparoscopy should be expedited to avoid delays in diagnosis.}, } @article {pmid40178731, year = {2025}, author = {Aujayeb, A and Astoul, P and Londero, F and Zuin, A}, title = {The Role of Surgery in Pleural Mesothelioma: A Journey through the Evidence, MARS 2 and Beyond.}, journal = {Pulmonary therapy}, volume = {}, number = {}, pages = {}, pmid = {40178731}, issn = {2364-1746}, abstract = {Pleural mesothelioma (PM) is a rare incurable disease, predominantly linked to asbestos exposure. Not only is diagnosis difficult, but treatment choices are often limited to systemic anti-cancer treatment with chemotherapy or immunotherapy. Surgery has been employed for decades, but its application has been fiercely debated despite some randomized controlled trials such as the recent Mesothelioma and Radical Surgery 2 (MARS 2) study. We provide a commentary on this controversial topic.}, } @article {pmid40166649, year = {2025}, author = {Goodman, JE and Rhomberg, LR and Cohen, SM and Mundt, KA and Case, B and Burstyn, I and Becich, MJ and Gibbs, G}, title = {Challenges in defining thresholds for health effects: some considerations for asbestos and silica.}, journal = {Frontiers in epidemiology}, volume = {5}, number = {}, pages = {1557023}, pmid = {40166649}, issn = {2674-1199}, abstract = {This paper summarizes several presentations in the Thresholds in Epidemiology and Risk Assessment session at the Monticello III conference. These presentations described evidence regarding thresholds for particles, including asbestos and silica, and cancer (e.g., mesothelioma) and noncancer (e.g., silicosis) endpoints. In the case of exposure to various types of particles and malignancy, it is clear that even though a linear non-threshold model has often been assumed, experimental and theoretical support for thresholds exist (e.g., through particle clearance, repair mechanisms, and various other aspects of the carcinogenic process). For mesothelioma and exposure to elongate mineral particles (EMPs), there remains controversy concerning the epidemiological demonstration of thresholds. However, using data from the Québec mining cohort studies, it was shown that a "practical" threshold exists for chrysotile exposure and mesothelioma. It was also noted that, in such evaluations, measurement error in diagnosis and exposure assessment needs to be incorporated into risk analyses. Researchers were also encouraged to use biobanks that collect specimens and data on mesothelioma to more precisely define cases of mesothelioma and possible variants for cases of all ages, and trends that may help define background rates and distinguish those mesotheliomas related to EMP exposures from those that are not, as well as other factors that support or define thresholds. New statistical approaches have been developed for identifying and quantifying exposure thresholds, an example of which is described for respirable crystalline silica (RCS) exposure and silicosis risk. Finally, the application of Artificial Intelligence (AI) to considering the multiple factors influencing risk and thresholds may prove useful.}, } @article {pmid40143456, year = {2025}, author = {Roggli, VL and Novakovic, S and Ghio, AJ and Li, H and Pina-Oviedo, S and Carney, JM and Sporn, TA and Glass, CH and Pavlisko, EN}, title = {Recent trends in the causation of peritoneal mesothelioma: fiber burden analysis of ten cases.}, journal = {Ultrastructural pathology}, volume = {}, number = {}, pages = {1-8}, doi = {10.1080/01913123.2025.2483226}, pmid = {40143456}, issn = {1521-0758}, abstract = {Mesothelioma in the past has been strongly associated with a history of asbestos exposure. Studies have shown that, on average, a higher dose of asbestos exposure is required for the development of peritoneal mesothelioma, and a smaller percentage of cases are asbestos related. Non-asbestos-related causes have been reported, including prior therapeutic radiation, genetic predisposition, and chronic inflammation (e.g. Crohn disease, endometriosis, ventriculo-peritoneal shunts, and diverticulitis). Cases in children have also been reported. Recent studies have shown a decreasing trend in fiber burdens and percentage of asbestos-related mesotheliomas, with similar observations in epidemiological studies. We performed fiber burden analysis on lung tissue in 10 cases (six men, four women) of peritoneal mesothelioma since 2010. Fiber analysis was performed using the sodium hypochlorite digestion technique, with asbestos body concentrations determined by light microscopy. Fiber concentrations and types were determined by scanning electron microscopy. The median age for the six men was 62 years (range: 53-75 years). Three cases were epithelioid type and three were biphasic. Two of six cases (33%) had an elevated lung fiber burden, with one case exclusively crocidolite and the other predominately amosite. The median age for the four women was 55 years (range: 39-63 years). Two cases were epithelioid type and two were biphasic. None of the four had an elevated lung fiber burden. Our findings are consistent with contemporary epidemiological studies indicating that a minority of peritoneal mesotheliomas occurring in men are asbestos related and very few are asbestos related in women.}, } @article {pmid40141249, year = {2025}, author = {Zacchi, P and Longo, F and Marconato, A and Amadei, M and Bonaccorsi di Patti, MC and Avolio, E and Li, P and Fan, H and Tetley, TD and Zabucchi, G and Borelli, V}, title = {Functional Characterization of the Hephaestin Variant D568H Provides Novel Mechanistic Insights on Iron-Dependent Asbestos-Induced Carcinogenesis.}, journal = {International journal of molecular sciences}, volume = {26}, number = {6}, pages = {}, doi = {10.3390/ijms26062607}, pmid = {40141249}, issn = {1422-0067}, support = {Liberal donation//Associazione Esposti Amianto (AEA) Monfalcone (Gorizia)/ ; Liberal donation//Lega Italiana per la Lotta contro i Tumori (LILT)- Associazione Provinciale Isontina Monfalcone (Gorizia)/ ; Internship award (APPID 3087)//Instruct-ERIC (PID 27484)/ ; }, mesh = {Humans ; *Iron/metabolism ; *Ceruloplasmin/metabolism/genetics ; *Cation Transport Proteins/metabolism/genetics ; *Membrane Proteins/metabolism/genetics ; *Asbestos/toxicity ; Carcinogenesis/metabolism/genetics/chemically induced ; Lung Neoplasms/metabolism/chemically induced/genetics/etiology/pathology ; Lung/metabolism/pathology ; }, abstract = {A local disruption of iron homeostasis leading to oxidative stress is considered one of the main mechanisms of asbestos-related genotoxicity. Another aspect contributing to the risk of developing pathological consequences upon asbestos exposure is individual genetic factors. In a previous study, we identified a coding SNP in the hephaestin gene (HEPH) that protects against developing asbestos-related thoracic cancer. Heph is a ferroxidase that promotes iron export in concert with the permease ferroportin (Fpn1). Here, we performed an in-depth functional characterization of the HephD568H variant to gain insights into the molecular basis of its protective activity. We showed that HephD568H forms a complex with Fpn1 and possesses full ferroxidase activity. Although HephD568H is more efficiently recruited to the plasma membrane, it is impaired in binding iron-deficient Tfn, whose interaction with wild-type (WT) ferroxidase emerged as a novel mechanism to perceive brain iron needs. Heph is expressed in the human lung by pericytes and fibroblasts, and lung pericytes were shown to respond to iron demand by upregulating the iron exporter pair. These results extend the paradigm of local iron regulation discovered at the blood-brain barrier to the pulmonary vasculature. Furthermore, they establish a mechanistic link between changes in iron sensing and the risk of developing asbestos-related malignancies.}, } @article {pmid40121357, year = {2025}, author = {Reid, G and Williams, M and Cheng, YY and Sarun, K and Winata, P and Kirschner, MB and Mugridge, N and Weiss, J and Molloy, M and Brahmbhatt, H and MacDiarmid, J and van Zandwijk, N}, title = {Therapeutic potential of synthetic microRNA mimics based on the miR-15/107 consensus sequence.}, journal = {Cancer gene therapy}, volume = {}, number = {}, pages = {}, pmid = {40121357}, issn = {1476-5500}, support = {11/TPG/3-06//Cancer Institute NSW (Cancer Institute New South Wales)/ ; }, abstract = {MicroRNA expression is frequently suppressed in cancer, and previously we demonstrated coordinate downregulation of multiple related microRNAs of the miR-15/107 group in malignant pleural mesothelioma (PM). From an alignment of the miR-15 family and the related miR-103/107, we derived a consensus sequence and used this to generate synthetic mimics. The synthetic mimics displayed tumour suppressor activity in PM cells in vitro, which was greater than that of a mimic based on the native miR-16 sequence. These mimics were also growth inhibitory in cells from non-small cell lung (NSCLC), prostate, breast and colorectal cancer, and sensitised all cell lines to the chemotherapeutic drug gemcitabine. The increased activity corresponded to enhanced inhibition of the expression of target genes and was associated with an increase in predicted binding to target sites, and proteomic analysis revealed a strong effect on proteins involved in RNA and DNA processes. Applying the novel consensus mimics to xenograft models of PM and NSCLC in vivo using EGFR-targeted nanocells loaded with mimic led to tumour growth inhibition. These results suggest that mimics based on the consensus sequence of the miR-15/107 group have therapeutic potential in a range of cancer types.}, } @article {pmid40115062, year = {2025}, author = {Seca, M and Cho, BCJ and Tryon, A and Narod, SA}, title = {A woman with a pleural mesothelioma and an inherited ATM mutation-a case report.}, journal = {Annals of translational medicine}, volume = {13}, number = {1}, pages = {8}, pmid = {40115062}, issn = {2305-5839}, abstract = {BACKGROUND: Pleural mesothelioma (PM) is a rare and aggressive malignancy primarily linked to asbestos exposure. Up to 80% of patients have a history of such exposure. Several studies have investigated the possibility of a genetic predisposition for a subgroup of PM patients, but the data remains inconsistent. The ataxia-telangiectasia mutated (ATM) gene, crucial for DNA repair, is implicated in cancer susceptibility, with heterozygous mutations increasing risks, notably in breast and pancreatic cancers.

CASE DESCRIPTION: We present a case of a 42-year-old woman, with no asbestos exposure history, diagnosed with metastatic PM. Initial treatment with immunotherapy showed limited efficacy. Given the rarity in young females, she opted for genetic testing via "The Screen Project", revealing a pathogenic ATM mutation. Due to enhanced radiosensitivity in ATM mutation carriers, to reduce adverse events conventional palliative radiotherapy (RT) was chosen over stereotactic hypofractionated RT. A follow-up computed tomography (CT) scan after 4 weeks indicated disease burden reduction.

CONCLUSIONS: This case highlights the importance of genetic testing in atypical PM cases, guiding treatment decisions tailored to individual genetic profiles. Awareness of ATM mutations can optimize therapeutic strategies, particularly regarding RT choices, in managing this challenging malignancy. Integrating genetic insights into clinical practice holds promise for enhancing treatment outcomes and refining management strategies in PM and related conditions.}, } @article {pmid40095514, year = {2025}, author = {Baratella, E and Ercolani, E and Segalotti, A and Troian, M and Lovadina, S and Giudici, F and Minelli, P and Ruaro, B and Salton, F and Cova, MA}, title = {Prognostic Value of Chest CT Volumetric Analysis in Patients with Malignant Pleural Mesothelioma.}, journal = {Journal of clinical medicine}, volume = {14}, number = {5}, pages = {}, doi = {10.3390/jcm14051547}, pmid = {40095514}, issn = {2077-0383}, abstract = {Background/Objectives: Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer linked to asbestos exposure and with poor overall survival. In recent years, CT volumetric analysis has gained increasing interest as a more accurate method for assessing tumor burden. This study aims to evaluate the prognostic value of chest CT volumetric analysis in MPM, comparing tumor volume with tumor thickness measurements and survival outcomes. Methods: This is a retrospective, observational analysis of all patients undergoing diagnostic thoracoscopy between 2014 and 2021 at the University Hospital of Cattinara (Trieste, Italy). Inclusion criteria were as follows: age ≥ 18 years, histological diagnosis of MPM, and the availability of at least one contrast-enhanced chest CT scan at the time of diagnosis. For each patient, the tumor thickness was measured on the axial plane at three levels (upper, middle, and lower hemithorax). Tumor and effusion volumes were calculated with the RayStation[®] software version 11.7.174 (HealthMyne[®], Madison, WI, USA). Results: A total of 81 patients were eligible for analysis. Maximum and mean tumor thickness were strongly associated with survival, with higher thicknesses correlating with an increased risk of death (adjusted hazard ratio per doubling (aHR) of 1.97 (95%CI: 1.40-2.77) and of 2.23 (95%CI: 1.56-3.20), p < 0.001)), respectively, while the effect of the tumor volume on survival was nevertheless significant but less impactful (aHR = 1.26 (1.10-1.45, p < 0.001)). The presence and volume of effusion did not correlate with survival (p = 0.48 and p = 0.64, respectively). Conclusions: This study supports the role of quantitative parameters for staging MPM, particularly given the frequent discrepancies between clinical and pathological staging when relying solely on qualitative measures.}, } @article {pmid40065797, year = {2025}, author = {Jayabalan, D and Donaghy, M and Charlesworth, C and Fysh, E and Lee, YCG}, title = {Miliary Mesothelioma.}, journal = {Respirology case reports}, volume = {13}, number = {3}, pages = {e70141}, doi = {10.1002/rcr2.70141}, pmid = {40065797}, issn = {2051-3380}, abstract = {Miliary spread of mesothelioma is a rare but important manifestation of late-stage disease, likely due to hematogenous dissemination. This case highlights characteristic CT imaging findings, emphasizing the need for awareness among clinicians and radiologists. Recognizing this pattern can aid in diagnosis, prognostication, and appropriate referral for palliative management.}, } @article {pmid40061543, year = {2025}, author = {Barreto, I and Franckenberg, S and Frauenfelder, T and Opitz, I and Lauk, O}, title = {Potential advantage of magnetic resonance imaging in detecting thoracic wall infiltration in pleural mesothelioma: A retrospective single-center analysis.}, journal = {JTCVS open}, volume = {23}, number = {}, pages = {318-325}, pmid = {40061543}, issn = {2666-2736}, abstract = {OBJECTIVES: Thoracic wall infiltration in pleural mesothelioma determines the extent of resection and can be an important prognostic factor. Currently, standardized imaging for restaging after neoadjuvant systemic therapy comprises contrast-enhanced computed tomography or positron emission tomography. Additional thoracic magnetic resonance imaging could better discriminate chest wall infiltration preoperatively and increase staging accuracy. For this reason, the added benefit of magnetic resonance imaging was evaluated at our center.

METHODS: A retrospective analysis of the extended imaging protocol was performed from July 2018 to March 2024, including a descriptive analysis for the patient's sex, age, tobacco consumption, asbestos exposure, histological subtype, TNM stage, Modified Response Evaluation Criteria for Solid Tumors in solid tumors, and number of neoadjuvant therapy cycles. Preoperative restaging included routine imaging and magnetic resonance imaging. After histological diagnosis of pleural mesothelioma, neoadjuvant therapy was conducted, followed by intended macroscopic complete resection, with intraoperative biopsies of suspicious chest wall lesions. Computed tomography and magnetic resonance imaging results were compared with intraoperative biopsies.

RESULTS: Twenty-six patients (mean age, 65.50 years, 11.50% female) with operable pleural mesothelioma were included. Of the 11 patients with histologically proven chest wall infiltration, 10 (90.91%) had a cT-stage 3 or greater and 4 (36.36%) underwent surgery that resulted in an R2 resection. Thoracic magnetic resonance imaging showed a high sensitivity (90.91%) for the detection of chest wall infiltration, especially when compared with the computed tomography scan (9.09%).

CONCLUSIONS: With the adjunctive use of magnetic resonance imaging, we demonstrated a higher sensitivity for detection of chest wall infiltration compared with conventional imaging before surgery. This may improve patient selection for surgery. Nevertheless, larger studies are required to confirm these results.}, } @article {pmid40056733, year = {2025}, author = {Kinoshita, R and Takeda, N and Kiyotoshi, H and Sugihara, M and Kuriyama, M and Nakao, M and Tsuyuki, T and Muramatsu, H}, title = {Sarcomatoid pleural mesothelioma evaluated using diffusion-weighted whole-body imaging with background body signal suppression.}, journal = {Respiratory investigation}, volume = {63}, number = {3}, pages = {323-325}, doi = {10.1016/j.resinv.2025.02.013}, pmid = {40056733}, issn = {2212-5353}, abstract = {An 83-year-old man with a history of asbestos exposure presented with dyspnea. Thoracic computed tomography showed right-sided pleural effusion and heterogeneous pleural thickening with calcified plaques. Thoracentesis revealed exudative fluid, and the cytology results were negative for malignancy. He didn't want to undergo invasive biopsy for pathological diagnosis. Diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) detected signal enhancement in the pleural thickening, ruling out metastasis. The patient died after one month, and sarcomatoid pleural mesothelioma was confirmed by autopsy. DWIBS is free of radioactive materials and can be used to evaluate lesion spread and metastases in hospitals equipped with magnetic resonance imaging.}, } @article {pmid40036898, year = {2025}, author = {DeBono, NL and Everest, L and Richardson, DB and Berriault, C and Yeo, RE and Meeds, MA and Arrandale, V and Demers, PA}, title = {Impact of Interventions to Prevent Asbestos-Related Respiratory Disease in an Exposed Worker Registry Using a Simplified G-computation.}, journal = {American journal of epidemiology}, volume = {}, number = {}, pages = {}, doi = {10.1093/aje/kwaf040}, pmid = {40036898}, issn = {1476-6256}, abstract = {The Ontario Asbestos Workers Registry is a regulatory exposure registry obligating employers to report the number of work hours with asbestos containing materials for each of their workers. Currently, each worker is notified of the need for a medical examination once they have accrued 2,000 reported hours of work with asbestos. We sought to evaluate the impact on disease prevention of alternative policies limiting asbestos work hours among registry participants. A cohort of 26,164 asbestos workers were followed for cancer and non-malignant disease diagnoses between 1986 and 2019. Analyses of the association between cumulative asbestos work hours and respiratory disease incidence rates showed substantially elevated disease rates well before reaching 2,000 asbestos work hours. Using a simplified application of parametric G-computation (G-POSH), limiting cumulative asbestos work hours to 100 hours would have prevented 76 asbestosis, 36 pulmonary fibrosis, 27 mesothelioma, and 79 lung cancer cases at the end of follow-up compared to the observed risk in the cohort. Limiting exposure to 2,000 asbestos work hours had a smaller but still substantial impact on disease prevention, particularly among workers in the construction industry. Regulatory agencies should intervene sooner to prevent respiratory disease among workers in the registry.}, } @article {pmid40034201, year = {2025}, author = {Takano, T and Sato, S and Ito, I and Yamamoto, M and Tsukioka, K and Matsumura, Y and Kono, T}, title = {Rare Metastatic Mesothelioma Occupying Intra-Atrial Cavity, Released by an Emergency Surgery: A Case Report and Literature Review.}, journal = {Surgical case reports}, volume = {11}, number = {1}, pages = {}, pmid = {40034201}, issn = {2198-7793}, abstract = {INTRODUCTION: Cardiac surgery for cardiovascular-associated mesothelioma has a poor prognosis. However, life-saving surgery is unavoidable to maintain circulation. This report describes a case in which metastatic intracardiac mesothelioma triggered sudden respiratory failure, which was reduced by surgical resection.

CASE PRESENTATION: An 81-year-old man with a history of asbestos exposure presented to our hospital with sudden onset of dyspnea. Prior to this event, the pleura was involved in an epithelial malignancy, which was immunohistochemically negatively stained with anti-D2-40, WT-1, or anti-calretinin antibodies, which are positive markers of mesothelioma. Transthoracic echocardiography revealed a fragile and mobile tumor occupying the right atrium, and the patient was admitted for surgical tumorectomy. The operation was performed urgently using a cardiopulmonary bypass via a full sternotomy. The pericardium is grossly intact and does not adhere to the heart. A 3 × 5 cm tumor was tightly attached to the right atrium and was large enough to fit into the tricuspid valve. Therefore, the entire margin of the tumor stem attachment was resected from the lateral wall of the right atrium. Although the resected tumor was not positive for any of the three histopathological markers of mesothelioma, CDKN2A co-deletion revealed by fluorescence in situ hybridization led to a diagnosis of malignant mesothelioma.

CONCLUSIONS: Surgical removal of intracardiac tumors that cause circulatory and respiratory instability is essential for the prevention of sudden death, regardless of prognostic determinants. This case demonstrates that mesotheliomas can metastasize to the endocardium. Even when nuclear atypia and negative results for immunohistochemical tests for the three mesothelioma markers suggest carcinoma, mesothelioma should still be considered and p16/CDKN2A co-deletion should be evaluated.}, } @article {pmid40017229, year = {2025}, author = {Prabhakaran, S and Hocking, AJ and Irani, Y and Hussey, M and Alexeyenko, A and Dobra, K and Micsik, T and Duhig, E and Walts, AE and Vanwalleghem, L and Chhut, V and Roden, AC and Roggli, VL and Hertoghs, M and Galateau-Salle, F and Brcic, L and Moffat, D and Klebe, S}, title = {An Evaluation Into the Robustness of Grading of Pleural Mesothelioma Outside of Specialist Centres.}, journal = {APMIS : acta pathologica, microbiologica, et immunologica Scandinavica}, volume = {133}, number = {3}, pages = {e70006}, pmid = {40017229}, issn = {1600-0463}, support = {//Flinders University/ ; }, mesh = {Humans ; *Pleural Neoplasms/pathology/diagnosis ; *Neoplasm Grading ; *Mesothelioma/pathology/diagnosis ; Male ; Female ; Middle Aged ; Mesothelioma, Malignant/pathology/diagnosis ; Pathologists ; Aged ; Surveys and Questionnaires ; Prognosis ; Necrosis ; }, abstract = {The 2021 WHO classification of thoracic tumours recommends grading pleural mesothelioma to aid prognostication. Robustness of grading and morphological characterisation is key to its clinical utility, though validation of this grading system has largely been conducted by expert thoracic pathologists. We conducted a survey inviting pathologists across a range of practices and expertise to grade digitised images of 50 epithelioid pleural mesotheliomas that had been graded by an expert in thoracic pathology. We included slides that were considered potentially problematic such as small biopsies, focal necrosis, and rare subtypes that may affect grading (small cell and deciduoid features). Using the Sectra Uniview web viewer, participants were asked to score atypia, mitotic count, and necrosis and choose from a list of cytological and architectural features. Seventy-four pathologists anonymously participated. There was 90% agreement of consensus scores with expert opinion using the WHO 2-tier grade and 72% for the 3-tier nuclear grade but only 70% for nuclear atypia, 56% for mitoses, and 84% for necrosis. Both 3-tier nuclear grade and WHO 2-tier grading systems were significantly associated with survival. Our study affirms the overall robustness and utility of grading for pleural mesothelioma, reveals variances, and suggests the need for dedicated training.}, } @article {pmid40009063, year = {2025}, author = {Brew, DW and Stevens, ME and Langer, AM and Paustenbach, DJ}, title = {A risk assessment of mechanics who changed chrysotile asbestos containing brakes and other vehicle components in the 1950s-early 2000s era: an update on the 2004 evaluation.}, journal = {Critical reviews in toxicology}, volume = {}, number = {}, pages = {1-50}, doi = {10.1080/10408444.2024.2427222}, pmid = {40009063}, issn = {1547-6898}, abstract = {For the past 50 years, there has been an ongoing interest in understanding the potential health hazards, if any, to vehicle mechanics who worked with asbestos-containing brakes in the 1950s-early 2000s era. Two reviews have been published on this topic, one by Langer (2003) ("Reduction of the biological potential of chrysotile asbestos arising from conditions of service on brake pads") and another by Paustenbach, et al. (2004) ("Environmental and occupational health hazards associated with the presence of asbestos in brake linings and pads (1900 to present): a 'state-of-the-art' review"). This analysis is an update on those papers since a considerable amount of research has been published over the past 20 years on this topic. The following important aspects are addressed in this review: new information on the toxicology of chrysotile, toxicology studies of brake dust associated with grinding, additional epidemiology studies and meta-analyses published on auto mechanics of the era, previously unfound data on how brakes (during the era when chrysotile was used) were manufactured, and new work describing the transformation of chrysotile to various degradation products during vehicle braking. This update also addresses questions about the health hazards associated with asbestos in vehicle clutches, transmissions, and gaskets. The exposure data indicate that the airborne concentrations of chrysotile fibers associated with vehicle mechanic work when asbestos was in auto brakes were, on average, less than 0.04 f/cm[3] (8-h TWA) and the average lifetime cumulative dose was in the vicinity of 0.5-3 f/cm[3]-year for mechanics of that era. Although many of these fibers may have no toxicity due to thermal degradation and the conversion to degradation products, 31 epidemiology studies have evaluated the risks of mesothelioma for vehicle mechanics of this era and all but one indicate that there was no increased incidence of this disease in these workers. The weight of evidence continues to indicate that the asbestos-related health risks to vehicle mechanics from asbestos-containing components were de minimis. The risks associated with take-home and bystander exposure of a mechanic were also addressed and they were found to pose a de minimis or zero health risk to those potentially exposed. Based on our evaluation, there is no indication that asbestos from asbestiform tremolite was present at detectable concentrations in bulk samples of brakes or in the air during brake work. The recent U.S. Environmental Protection Agency (EPA) risk assessment of 2024 on chrysotile and their views of the hazards of asbestos-containing brakes were discussed. Their analyses did not alter our views that exposures to mechanics posed no increased risk of asbestos related disease. The latest knowledge about the role of genetic susceptibility on the development of mesothelioma is also addressed.}, } @article {pmid40006597, year = {2025}, author = {Stebletsova, IA and Larin, AA and Matnurov, EM and Ananyev, IV and Babak, MV and Fershtat, LL}, title = {Exploring the Anticancer Potential of NO-Donor Oxadiazole Assemblies Against Malignant Pleural Mesothelioma.}, journal = {Pharmaceutics}, volume = {17}, number = {2}, pages = {}, doi = {10.3390/pharmaceutics17020230}, pmid = {40006597}, issn = {1999-4923}, support = {9211315//Pneumoconiosis Compensation Fund Board of Hong Kong/ ; 19-73-20074-P//Russian Science Foundation/ ; }, abstract = {Background: Nitric oxide (NO) has been linked to the pathogenesis of asbestos-related pleural diseases, including an extremely aggressive cancer called malignant pleural mesothelioma (MPM). Given that MPM cells are characterized by a higher expression of NO synthases and elevated NO production relative to normal cells, the use of NO-donor compounds could potentially saturate the cancerous cells with NO, triggering their death. Methods: We developed a novel class of NO prodrugs by merging two NO-releasing components, 1,2,5-oxadiazole 2-oxides (furoxans) and 1,2,4-oxadiazoles, and studied their NO-releasing characteristics in a time-dependent manner using the Griess assay. The cytotoxicity against two human MPM cell lines and non-cancerous lung fibroblasts was evaluated using a colorimetric MTT assay. Results: All compounds exhibited excellent NO-donating properties, surpassing the capacity of two reference NO donor compounds, 3-carbamoyl-4-(hydroxymethyl)furoxan (CAS-1609) and 4-ethoxy-3-phenylsulphonylfuroxan (CHF-2363), by at least 1.5-3 times. All oxadiazole hybrids demonstrated high cytotoxicity against MPM cell lines in a low micromolar range, comparable or higher than the cytotoxicity of the standard-of-care drug cisplatin. Conclusions: Notably, the novel compounds displayed a markedly greater selectivity towards cancerous cells than cisplatin when compared with non-cancerous lung fibroblasts, aligning with the intended design.}, } @article {pmid40003441, year = {2025}, author = {Singh, R and Fitzgerald, S and Dada, R and Frank, AL}, title = {Marble Waste Dump Yard in Rajasthan, India Revealed as a Potential Asbestos Exposure Hazard.}, journal = {International journal of environmental research and public health}, volume = {22}, number = {2}, pages = {}, doi = {10.3390/ijerph22020215}, pmid = {40003441}, issn = {1660-4601}, mesh = {India ; *Asbestos/analysis ; Humans ; Environmental Exposure ; Waste Disposal Facilities ; Asbestos, Amphibole/analysis/toxicity ; Dust/analysis ; }, abstract = {Asbestos is a fibrous variety of certain minerals, some of which occur naturally as an accessory to a wide variety of mineral resources. Although asbestos itself has been historically mined for various useful properties, the negative health effects of asbestos dust have greatly diminished it as a useful earth material, as many countries have banned the use of these fibrous minerals based on those health concerns. Resulting regulations of asbestos have focused primarily on intentionally mined material used in product manufacturing, such as building materials made with beneficiated asbestos and their derivative exposures, e.g., airborne asbestos in schools with asbestos-containing materials. The hazards of asbestos as unintended byproducts have not been as extensively considered, although this "contamination" has been repeatedly observed in common earth materials including talc, vermiculite, sand, and gravel. This study reveals such contamination of ornamental and dimension stone commonly referred to as "marble". Asbestos types that can be associated with certain Indian marble reserves include asbestiform tremolite, actinolite, anthophyllite, and chrysotile asbestos. This case reveals such contamination in a marble reserve in Rajsamand, Rajasthan. At this location, marble dust in slurry is disposed at waste collection points, unfortunately including a location now open to the public that has become a tourist destination. Using Transmission Electron Microscopy (TEM) in this study, dust from this location revealed abundant tremolite asbestos fibres in the disaggregated dust. This poses potential health risks to the workers, bystanders, and tourists that may be exposed to this recognized carcinogen, a known cause of mesothelioma, lung cancer, and other asbestos-related diseases.}, } @article {pmid40002287, year = {2025}, author = {Suraya, R and Nagano, T and Tachihara, M}, title = {Recent Advances in Mesothelioma Treatment: Immunotherapy, Advanced Cell Therapy, and Other Innovative Therapeutic Modalities.}, journal = {Cancers}, volume = {17}, number = {4}, pages = {}, doi = {10.3390/cancers17040694}, pmid = {40002287}, issn = {2072-6694}, abstract = {Mesothelioma is a highly malignant condition arising from the pleura and peritoneum that is closely related to asbestos exposure. The prognosis for this condition has traditionally been poor due to the difficulty physicians have faced in diagnosing and treating this disease, even in its early phase. Fortunately, recent advances in both the molecular understanding of the development of this disease and innovative and novel treatment modalities have accelerated the discovery of new ways to treat mesothelioma. In this review, we first summarize the mechanism of mesothelioma pathophysiology and then relate it to emerging treatment modalities. These include immunotherapy or immune checkpoint inhibitors (ICIs), molecular targeted therapies, and cell-based therapies (such as CAR-T cells or dendritic cells). The scientific basis for the utilization of these treatment modalities, alongside the current clinical evidence for each option, will be explored in detail later on. The hope is that this review can elucidate how these emerging therapeutic options work clinically to help accelerate further developments in novel mesothelioma treatment modalities.}, } @article {pmid39989419, year = {2025}, author = {Angelini, A and Ricci, P and Mirabelli, D}, title = {[Risk apportionment to remote and recent asbestos exposures for pleural mesothelioma].}, journal = {Epidemiologia e prevenzione}, volume = {49}, number = {1}, pages = {In press}, doi = {10.19191/EP25.1.A762.002}, pmid = {39989419}, issn = {1120-9763}, mesh = {Humans ; *Asbestos ; *Mesothelioma/epidemiology/etiology ; *Pleural Neoplasms/epidemiology/etiology ; *Occupational Exposure/adverse effects ; Italy/epidemiology ; *Occupational Diseases/epidemiology/etiology ; Incidence ; Risk Assessment ; Middle Aged ; Time Factors ; Adult ; Male ; Aged ; Lung Neoplasms/epidemiology/etiology ; Female ; Aged, 80 and over ; }, abstract = {BACKGROUND: the exposure-response relationship between pleural mesothelioma and asbestos has been traditionally described by models that predicted incidence to increase indefinitely by latency. Studies with long observation showed that the increase flattens out beyond 40 years of latency. It has been, therefore, proposed to introduce an exponential decay function into the models Objectives: to show characteristics and implications as to the relevance of remote and recent exposures, by conducting a simulation exercise based on data available from the literature.

METHODS: the traditional and decay models that best fit mortality from pleural cancer during the initial 40 years of observation in the Italian pooled cohort of asbestos workers were selected. The mesothelioma incidence predicted by such models as a function of age at first exposure, exposure duration, and age at risk was compared. It was also compared the proportional weight assigned to remote, intermediate, and recent exposure, by dividing the whole exposure period in three parts of equal duration.

RESULTS: the decay, but not the traditional, model fits well the trend observed after 40 years. According to the traditional model, remote exposures have maximum and recent exposures minimum weight: for instance, following an exposure starting at age 20 and lasting 18 years, the incidence at age 80 would be attributed to remote exposures by 47% and by 21% to the recent ones. The decay model predicts only minor differences and even of reversed weight: 34% and 31%, respectively, in this case.

CONCLUSIONS: remote exposures do not necessarily have overwhelming weight in determining pleural mesothelioma risk. The balance between different exposure periods depends on the time-distribution of exposure.}, } @article {pmid39984959, year = {2025}, author = {Piccioni, M and Di Meo, F and Valentino, A and Campani, V and Arigoni, M and Tanori, M and Mancuso, M and Cuciniello, R and Tomasetti, M and Monaco, F and Goteri, G and Spugnini, EP and Calogero, RA and De Rosa, G and Peluso, G and Baldi, A and Crispi, S}, title = {miRNA-503 inhibition exerts anticancer effects and reduces tumor growth in mesothelioma.}, journal = {Journal of experimental & clinical cancer research : CR}, volume = {44}, number = {1}, pages = {65}, pmid = {39984959}, issn = {1756-9966}, support = {PNRR P2022RLH39//Ministero dell'Istruzione, dell'Università e della Ricerca/ ; P2022RZ8WM//Ministero dell'Università e della Ricerca/ ; G46C2000000009//Regione Basilicata/ ; F/180022/04/X43//Ministero dello Sviluppo Economico/ ; DBA.AD005.225//Consiglio Nazionale delle Ricerche/ ; }, abstract = {BACKGROUND: Malignant mesothelioma (MM) is a rare and aggressive form of cancer that affects the mesothelial surfaces, associated with exposure to asbestos fibres. To date, no cure is available for MM and therapeutically approved treatments are based on the use of platinum compounds often used in combination with other drugs. We have previously analysed the efficacy of a cisplatin/piroxicam (CDDP/P) combined treatment showing that this treatment was able to reduce in vivo tumor growth. Several studies reported that platinum-drug sensitivity in cancer is connected to modulation of the expression of non-coding RNAs. In this study we analysed if the CDDP/P treatment was able to modulate miRNAs expression in MM.

METHODS: miRNA sequencing performed on MSTO-211 H cells treated with CDDP with CDDP/P led us to identify miRNA-503 - downregulated by CDDP/P - as a novel miRNA that acts as an oncomiR in MM. The effect of miRNA-503 inhibition was evaluated in vitro in mesothelioma cells analysing apoptosis induction and reduction of cancer properties. Inhibition of miR-503 expression in vivo, was analysed in ectopic mouse model of MM by using LNP encapsulating anti-mir-503 and miR-503 expression was evaluated in human MM samples.

RESULTS: In vitro and in vivo analysis confirmed miR-503 acts as oncogene in MM since its inhibition was able to reduce cell cancer properties and tumor growth in ectopic mouse model of MM. Its expression was found upregulated in human MM patients compared to normal pleura. Bioinformatic analysis indicated BTG1, CCNG1, EDG1, and TIMP2 as putative target genes of miRNA-503. These genes showed an opposite expression compared to miR-503 levels both in cells and in MM samples. Finally, microarray analysis indicated that miR-503 inhibition affected the expression of the well-known MM biomarkers: CXCL8, SERPINE1 and Osteopontin.

CONCLUSIONS: Our study is the first reporting an oncomiR role for miR-503 in MM and suggests that its inactivation could have a clinical value in MM patients. This study reveals that miRNA-503 acts as an oncomiR in MM suggesting that its inhibition, through LNP delivery, has the potential to be considered as a novel therapeutic strategy in MM.}, } @article {pmid39983469, year = {2025}, author = {Fukui, T and Sumitomo, R and Menju, T and Kobayashi, M and Sakai, H and Date, H}, title = {M2-like tumor-associated macrophages may promote tumor progression in malignant pleural mesothelioma.}, journal = {Translational oncology}, volume = {54}, number = {}, pages = {102324}, doi = {10.1016/j.tranon.2025.102324}, pmid = {39983469}, issn = {1936-5233}, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is an aggressive malignancy with an unfavorable prognosis. Asbestos-activated macrophages may contribute to both oncogenesis and progression of MPM. This study aimed to clarify the biological and clinical significance of M2-like tumor-associated macrophages (TAMs) in MPM.

METHODS: This retrospective study included 101 MPM patients who were diagnosed and started treatment between 1998 and 2010. The distribution of M2-like TAMs in the intratumoral and peritumoral regions was evaluated by immunohistochemistry using CD163 staining. Tumor proliferation was evaluated by Ki-67 staining.

RESULTS: Intratumoral M2-like TAM density was significantly correlated with the pretreatment C-reactive protein level (r = 0.283, P = 0.004) and Ki-67 proliferation index (r = 0.498, P < 0.001). Peritumoral M2-like TAM density was also significantly correlated with the pretreatment C-reactive protein level (r = 0.255, P = 0.010) and Ki-67 proliferation index (r = 0.435, P < 0.001). Additionally, intratumoral M2-like TAM density was associated with histological subtype (P < 0.001), with higher densities observed in sarcomatoid tumors compared to epithelioid tumors. The overall survival rate was significantly worse in the intratumoral and peritumoral M2-like TAM-high groups (P = 0.044 and P = 0.046, respectively), particularly in patients with advanced-stage MPM. Multivariable analysis identified peritumoral M2-like TAM status (hazard ratio = 1.700, 95 % confidence interval: 1.034-2.796, P = 0.037), clinical stage, and histology as significant prognostic factors for overall survival.

CONCLUSIONS: During MPM progression, M2-like TAMs may induce tumor cell proliferation and aggressiveness, contributing to the poor prognosis in MPM patients.}, } @article {pmid39981889, year = {2025}, author = {Andreikos, D and Spandidos, DA and Georgakopoulou, VE}, title = {Telomeres and telomerase in mesothelioma: Pathophysiology, biomarkers and emerging therapeutic strategies (Review).}, journal = {International journal of oncology}, volume = {66}, number = {3}, pages = {}, doi = {10.3892/ijo.2025.5729}, pmid = {39981889}, issn = {1791-2423}, mesh = {Humans ; *Telomerase/genetics/metabolism ; *Biomarkers, Tumor/genetics/metabolism ; *Telomere/genetics/metabolism ; *Mesothelioma, Malignant/genetics/pathology/drug therapy ; Mesothelioma/genetics/pathology ; Lung Neoplasms/genetics/pathology ; Prognosis ; Polymorphism, Single Nucleotide ; Mutation ; Promoter Regions, Genetic ; }, abstract = {Malignant mesothelioma (MM) is a rare but aggressive cancer linked to asbestos exposure and characterized by advanced‑stage disease at presentation. Despite advances in treatment, prognosis remains abysmal, highlighting the imperative for the development of novel biomarkers and treatment approaches. Telomere biology plays a pivotal role in the tumorigenic process and has emerged as a key area in oncology research. Short telomeres have been associated with genomic instability, and substantially shorter telomere length (TL) has been identified in MM, showcasing the potential of TL in risk assessment, early detection, and disease progression monitoring. MM predominantly maintains TL through telomerase activity (TA), which in research has been identified in >90% of MM cases, underscoring the potential of TA as a biomarker in MM. Telomerase reverse transcriptase (TERT) polymorphisms may serve as valuable biomarkers, with research identifying associations between single nucleotide polymorphisms (SNPs) and the risk and prognosis of MM. Additionally, TERT promoter mutations have been associated with poor prognosis and advanced‑stage disease, with the non‑canonical functions of TERT hypothesized to contribute to the development of MM. TERT promoter mutations occur in ~12% of MM cases; C228T, C250T and A161C are the most common, while the distribution and frequency differ depending on histological subtype. Research reveals the promise of the various approaches therapeutically targeting telomerase, with favorable results in pre‑clinical models and inconclusive findings in clinical trials. The present review examines the role of telomere biology in MM and its implications in diagnosis, prognosis, and therapy.}, } @article {pmid39973732, year = {2025}, author = {Tuncer, K and Gomleksiz, M}, title = {Improving asbestos knowledge among demolition workers through training after earthquakes.}, journal = {Work (Reading, Mass.)}, volume = {}, number = {}, pages = {10519815241305009}, doi = {10.1177/10519815241305009}, pmid = {39973732}, issn = {1875-9270}, abstract = {BACKGROUND: Asbestos was widely used as insulation material in Türkiye's construction. It poses severe health risks, including mesothelioma, a type of lung cancer that is often fatal.

OBJECTIVE: This study aimed to determine and improve the knowledge about asbestos among employees of a building demolition workers in Elazığ.

METHODS: Out of 82 employees in the demolition workers, 75 volunteered for the study after ethical approval was obtained. Training materials and survey forms were developed through a review of the literature. Surveys were conducted before and after the training sessions. Data were analyzed using SPSS 22.0, and a p-value of less than 0.05 indicated statistical significance.

RESULTS: The participants were exclusively male, with an average age of 39.06 years. Among them, 40% were current smokers. Most had not received prior training on asbestos. Before the training, nearly half of the respondents (49.4%) were unaware of the procedures for asbestos check and removal prior to demolition. knowledge across all surveyed areas. The knowledge of demolition workers increased significantly after training.

CONCLUSION: Training significantly improved asbestos-related knowledge which was low before among the demolition workers, a group at high risk for asbestos exposure.}, } @article {pmid39960454, year = {2025}, author = {Kanno, J}, title = {Carcinogenicity assessment: "Modern Toxicology" considerations from an experience in the evaluation of a carbon nanotube.}, journal = {Journal of occupational health}, volume = {}, number = {}, pages = {}, doi = {10.1093/joccuh/uiaf013}, pmid = {39960454}, issn = {1348-9585}, abstract = {The novel properties and functions of nanomaterials have naturally alerted the toxicologists to the fact that such materials may also have novel effects on the human body and living organisms. In particular, materials with high stability or biopersisteny have been shown to have a tendency to accumulate in the body, leading to chronic toxicity including carcinogenicity. However, at the early stages of toxicity research, the information is often limited to the effects of short-term exposure studies, and findings on chronic effects are very much delayed. In this context, it was rather exceptional that studies on multiwall carbon nanotubes (MWCNTs) have started with the verification of their potential to induce mesothelioma. This toxicological endpoint was expected on the basis of existing knowledge of asbestos and asbestos-like fiber particles. This movement has led to the achievement of the original mission of the "Modern Toxicology", which is "to achieve a win-win situation where both industrial promotion and safety assurance are ensured by communicating and sharing toxicity information to developers and consumers at a stage before mass production and consumption begins, that is, before massive exposure of the general public begins". Inaccurate toxicity assessments of asbestos in the 1980s and 1990s allowed its spread to our living environment, which is difficult to decontaminate, and the damage still continues to this day. However, the case described here could be an example of realizing the proposition that 'nanomaterials, the flagship of high technology, must not repeat the same mistakes.'}, } @article {pmid39958414, year = {2024}, author = {Salvado, A and Capone, L and Zamorano, P and Samudio, M and Garcia-de-Dávila, MT and Ernst, G}, title = {A comprehensive multidisciplinary approach for identifying asbestos exposure among underground workers.}, journal = {Revista brasileira de medicina do trabalho : publicacao oficial da Associacao Nacional de Medicina do Trabalho-ANAMT}, volume = {22}, number = {4}, pages = {e20241271}, pmid = {39958414}, issn = {1679-4435}, abstract = {INTRODUCTION: Inhalation of asbestos fibers can lead to a range of diseases, including asbestosis, pleural plaques, lung cancer, and malignant mesothelioma. Despite regulatory efforts, asbestos-related diseases remain a significant public health issue.

OBJECTIVES: This study aimed to assess the characteristics and prevalence of asbestos-related diseases among exposed workers.

METHODS: We conducted a descriptive cohort study with underground workers in Buenos Aires, Argentina, from March 2018 to March 2023. A comprehensive screening and surveillance program, including medical examinations, was implemented to identify exposure-related signs and symptoms. Histological sections from paraffin-embedded tissue blocks were analyzed using light and polarization microscopy for lung cancer cases.

RESULTS: A total of 2,690 participants were included, of whom 2.8% (n = 77) had asbestos-related diseases and 0.22% (n = 6) had lung cancer. Occupational exposure exceeding 20 years was significantly associated with an elevated risk of asbestos-related diseases (odd ratio: 3.02; 95%CI 1.7-5.3).

CONCLUSIONS: The prevalence of occupational diseases among underground workers was consistent with findings from other surveillance programs for asbestos-exposed workers. Occupational exposure exceeding 20 years emerged as a significant risk factor, markedly increasing the likelihood of asbestos-related diseases.}, } @article {pmid39947731, year = {2025}, author = {Rao D, P and Vijayan, S and Vananjakar, SS and T, PK}, title = {Malignant pleural mesothelioma.}, journal = {BMJ case reports}, volume = {18}, number = {2}, pages = {}, doi = {10.1136/bcr-2024-263562}, pmid = {39947731}, issn = {1757-790X}, mesh = {Humans ; Female ; *Mesothelioma, Malignant/diagnosis/pathology/therapy ; *Pleural Neoplasms/diagnosis/therapy ; Aged ; *Pleurodesis ; Mesothelioma/diagnosis/therapy/pathology ; Lung Neoplasms/diagnosis/pathology/therapy ; Palliative Care ; Talc/adverse effects/administration & dosage ; Thoracoscopy/methods ; Pleural Effusion, Malignant/etiology/therapy/diagnosis/diagnostic imaging ; Tomography, X-Ray Computed ; Dyspnea/etiology ; }, abstract = {Malignant pleural mesothelioma is a rare and aggressive tumour of the pleura, commonly linked to asbestos exposure. However, its diagnosis is challenging, especially without known exposure. We present the case of a woman in her early 70s with no history of asbestos exposure, who presented with progressive breathlessness and left-sided chest pain. Radiological assessment revealed a large pleural effusion and nodular pleural thickening. Malignant pleural mesothelioma was confirmed through histopathological analysis of biopsies obtained via medical thoracoscopy. The patient was initiated on a palliative chemotherapy regimen, underwent talc slurry pleurodesis for recurrent effusion, and is currently under follow-up. This case emphasises the importance of a high index of suspicion for malignant pleural mesothelioma in patients with unexplained pleural effusion, even in the absence of typical risk factors, and the need for a timely diagnosis due to the disease's dismal prognosis.}, } @article {pmid39939955, year = {2025}, author = {Shi, H and Yu, TK and Johnson, B and Selvamani, SP and Zhuang, L and Lee, K and Klebe, S and Smith, S and Wong, K and Chen, K and Clark, G and Rath, EM and Pearson, H and Ortega, DG and Linton, A and Kao, S and Silveira, P and Cheng, YY}, title = {A combination of PD-1 and TIGIT immune checkpoint inhibitors elicits a strong anti-tumour response in mesothelioma.}, journal = {Journal of experimental & clinical cancer research : CR}, volume = {44}, number = {1}, pages = {51}, pmid = {39939955}, issn = {1756-9966}, abstract = {BACKGROUND: Finding effective and curative treatment for mesothelioma remains challenging. While the introduction of immunotherapy combinations using ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) have offered hope for some patients, a large proportion of mesothelioma cases, particularly the epithelial subtype, have minimal benefit from this.

METHODS: Our study was inspired by the results of the AdvanTG-105 phase I clinical trial, which showed partial response with anti-TIGIT/PD-1 treatment in two epithelioid mesothelioma patients. Here, we conducted a comprehensive in vivo experiment involving eight animal treatment groups administered with either PBS (control group), cisplatin/pemetrexed, anti-PD-1, anti-PD-1 + anti-CTLA-4, anti-TIGIT, anti-PD-1 + anti-TIGIT, anti-PD-1 + anti-CTLA-4 + anti-TIGIT, and cisplatin/pemetrexed + anti-PD-1 + anti-TIGIT.

RESULTS: Our results indicate that animals receiving anti-PD-1 + TIGIT exhibited a superior anti-tumour response, with 90% of the treatment group exhibiting an objective response, compared to 60%, 20% and 40% for the standard-of-care anti-PD-1 + CTLA-4, single-agent anti-PD-1 and cisplatin/pemetrexed treatment groups, respectively. Animals receiving anti-PD-1 + TIGIT displayed a significantly reduced average tumour size, with improved weight and survival rates, and fewer adverse effects than those receiving anti-PD-1 + CTLA-4 treatment. Anti-PD-1 + TIGIT-treated animals achieved complete tumour regression, with heightened effector CD8 + T cell and NK cell activity, remaining tumour-free for over 300 days without immune-related adverse events. After initial tumour elimination, anti-PD-1 + TIGIT-treated animals showed no tumour regrowth in the rechallenge experiment.

CONCLUSION: These findings provide rationale for the development of an anti-PD-1 + TIGIT combination immunotherapy trial for mesothelioma patients.}, } @article {pmid39934006, year = {2025}, author = {Lopci, E}, title = {"Current Status of Staging and Restaging Malignant Pleural Mesothelioma".}, journal = {Seminars in nuclear medicine}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.semnuclmed.2025.01.003}, pmid = {39934006}, issn = {1558-4623}, abstract = {Malignant pleural mesothelioma (MPM) is the most frequent aggressive tumor affecting the pleura, accounting for over 38,000 deaths worldwide. It originates from the mesothelial cells and is mostly associated to asbestos exposure. Depending on the extent of the disease, the management of MPM varies from surgical intervention to a combination of systemic chemotherapy, immunotherapy, and radiation therapy. Major International scientific societies provide continuous updates on proper management of the disease, including recommendations on the optimal imaging algorithms, which are crucial for determining effective treatment options and optimizing clinical outcomes. However, despite the continuous efforts to improve patients' prognosis, median overall survival remains poor, ranging from 8 to 14 months. And even in case of initial response to treatment, local or distant recurrences represent almost a certainty, requiring appropriate imaging for the assessment of tumor sites. The aim of the present article is to illustrate the current status of imaging for staging and restaging of MPM, not forgetting most recent novelties in the diagnostic work-up of the disease.}, } @article {pmid39921204, year = {2025}, author = {Pandey, K and Faridi, P and Ayala, R and Lee, YCG and Rouse, E and Krishna, SSG and Dick, I and Redwood, A and Robinson, B and Creaney, J and Purcell, AW}, title = {Multiple classes of antigen contribute to the antigenic landscape of mesothelioma.}, journal = {Molecular & cellular proteomics : MCP}, volume = {}, number = {}, pages = {100925}, doi = {10.1016/j.mcpro.2025.100925}, pmid = {39921204}, issn = {1535-9484}, abstract = {Mesothelioma is an incurable, asbestos-exposure related cancer that typically affects the lining or pleura of the lungs. Symptoms typically develop many decades after initial exposure to asbestos, leaving an enduring legacy of disease. Current disease burden is peaking worldwide and thus there is a massive unmet clinical need for curative therapies. Recently, immune checkpoint blockade-based therapy has been adopted as a first-line of treatment for mesothelioma. Vaccine-induced augmentation of immune responses unleashed during checkpoint blockade may provide further clinical benefit in mesothelioma. In this study we explore the human leukocyte antigen class I landscape (or immunopeptidome) of mesothelioma in patient derived cell line and clinical material (pleural effusion samples). We identify a range of peptide antigens derived from targets including cancer testis antigens, endogenous retroviruses as well as novel post-translational modification of peptides. This information will facilitate the characterization of the immune response to these antigens to determine which class of antigen is most immunogenic and has the potential to be tested in future vaccine studies.}, } @article {pmid39911320, year = {2025}, author = {Korchevskiy, AA and Wylie, AG}, title = {Habit of elongate amphibole particles as a predictor of mesothelial carcinogenicity.}, journal = {Toxicology reports}, volume = {14}, number = {}, pages = {101908}, pmid = {39911320}, issn = {2214-7500}, abstract = {INTRODUCTION: Amphiboles are a class of minerals that are abundantly present in the environment. Amphiboles may exist in several habits, with asbestiform particles behaving like typical amphibole asbestos and non-asbestiform (or massive) reported to be less biologically active.

MATERIALS AND METHODS: The available dimensional information for 16 testing sets (8 asbestiform and 8 non-asbestiform types of tremolite) was combined. In addition, three validation sets (an asbestiform sample from Eastern New York and non-asbestiform samples from Quebec and Falls Village, Connecticut) were tested by Transmission Electron Microscopy (TEM) to determine dimensional distribution. Mathematical modeling was utilized to determine the classification method for amphiboles with various habits.

RESULTS: The decision boundary method was developed to distinguish asbestiform vs. non-asbestiform samples (with error rate of 0 % for single-sourced tremolite and 3 % for potentially mixed samples). All validation datasets were correctly classified. A new empirical dimensional coefficient of carcinogenicity (DCC) was proposed, with DCC = 1 - exp(-0.11 Surface Area /(1000width[3] + 1)). For several mineral types (crocidolite, amosite, Libby amphiboles, anthophyllite, chrysotile, and erionite), it was demonstrated that mesothelioma potency factors can be predicted based on DCC and biosolubility with a high level of accuracy (R=0.98, R[2]=0.96, p < 0.006). It was demonstrated that modeled mesothelioma potency correlates with relative potency for pleural instillation in Wistar rats, and correlates inversely with membranolytic toxicity index HC50. Mesothelioma potency was demonstrated to be negligible in all non-asbestiform sets.

CONCLUSIONS: The habit of amphibole particles is predictive of biological behavior that can be estimated from the dimensional data for the particles.}, } @article {pmid39871092, year = {2025}, author = {Toyokuni, S and Kong, Y}, title = {Decoding the Molecular Enigma Behind Asbestos and Fibrous Nanomaterial-induced carcinogenesis.}, journal = {Journal of occupational health}, volume = {}, number = {}, pages = {}, doi = {10.1093/joccuh/uiae064}, pmid = {39871092}, issn = {1348-9585}, abstract = {OBJECTIVES: Natural fibrous mineral, asbestos, has been useful in industry for many centuries. In the 1960's, epidemiology had recognized the association between asbestos exposure and mesothelioma and the IARC designated all kinds of asbestos as Group 1 in 1987. However, various scientific enigmas remained regarding the molecular mechanisms of asbestos-induced mesothelial carcinogenesis. This review article was undertaken to reveal and summarize the recent discoveries how the enigma has been resolved.

METHODS: We collected recent important findings of our own laboratory and the others to explain why mesothelial cells are the target for asbestos-induced carcinogenesis and what is the key molecular mechanisms.

RESULTS: Long incubation period of 30 ~ 40 years for mesothelial carcinogenesis after asbestos exposure is responsible for the asbestos fibers to go through the pulmonary parenchyma from the central to peripheral portions finally to reach the parietal mesothelium by piercing visceral pleura. Asbestos fibers have affinity for hemoglobin and histones, thus accumulating iron on the surface while travelling through the lung. The other important point is that mesothelial cells are phagocytic cells, engulfing iron-coated asbestos fibers. Accordingly, homozygous deletion of p16INK4a tumor suppressor gene, a signature of excess iron-induced carcinogenesis, is acquired through oxidative DNA damage. Recently, exosome-dependent iron transfer from asbestos-fed macrophages to mesothelial cells was reported. Similar molecular mechanisms are observed in multiwalled carbon nanotube of ~50-nm-diameter.

CONCLUSION: Physical dimension, biopersistence and affinity to iron/histones are essential for fibrous material to be carcinogenic to mesothelial cells. Therefore, local iron reduction maybe a strategy to prevent mesothelial carcinogenesis.}, } @article {pmid39867168, year = {2025}, author = {Jadhav, AV and Gawde, N and Veerappan, R and Choi, Y and Frank, AL}, title = {Understanding exposure risk using soil testing and GIS around an abandoned asbestos mine.}, journal = {Annals of global health}, volume = {91}, number = {1}, pages = {2}, pmid = {39867168}, issn = {2214-9996}, mesh = {*Mining ; Humans ; *Geographic Information Systems ; *Environmental Exposure/analysis ; India/epidemiology ; *Asbestos/analysis ; *Soil Pollutants/analysis ; Dust/analysis ; Soil/chemistry ; Asbestos, Serpentine/analysis ; Environmental Monitoring/methods ; Microscopy, Electron, Scanning ; }, abstract = {Background: Abandoned asbestos mines are a potential source of environmental contamination and exposure for nearby residents. The asbestos exposure risk may persist even after the cessation of mining activity if the mine is not properly closed. One such abandoned mine is at Roro Hills in the Jharkhand state of India. There are limited studies examining soil contamination and asbestos exposure to nearby residents due to abandoned mines. Objectives: The aim of this study is to examine the presence of asbestos in the residential areas of villages surrounding an abandoned asbestos mine and to understand the spread of visible asbestos dust using geographic information system map analysis. Methods: This study examined the presence of asbestos in soil samples from four villages surrounding an abandoned asbestos mine using the scanning electron microscopy technique. The study also compared satellite images taken 13 years apart to determine whether the mine waste containing asbestos had spread over time. Findings: The soil sample testing indicated that, out of 16 soil samples from residential areas, 12 showed the presence of chrysotile asbestos. It was found in the map analysis that asbestos-containing areas had enlarged by around 20% in those years. Conclusion: The evidence indicated the presence of asbestos in the soil of nearby residential areas around the mine, and this contamination has spread over the years. Similar studies at other mine locations are needed, and timely interventions are warranted to protect nearby residents.}, } @article {pmid39447855, year = {2024}, author = {Opitz, I and Lauk, O and Werner, R and Matter, A and Hebeisen, M and Battilana, B and Batirel, H and Pass, H and Flores, R and Wolf, A and de Perrot, M and Hoda, MA and Klepetko, W and Klikovits, T and Hashimoto, M and Hasegawa, S and Richards, WG and Bueno, R}, title = {Characteristics of Long-term Survivors With Malignant Pleural Mesothelioma.}, journal = {The Annals of thoracic surgery}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.athoracsur.2024.10.004}, pmid = {39447855}, issn = {1552-6259}, abstract = {BACKGROUND: Pleural mesothelioma (PM) is a cancer with a usually dismal prognosis. However, long-term survivors do exist. Herein, we analyzed long-term survivors (>5 years after surgery) from high-volume centers around the world.

METHODS: This is a multicenter retrospective descriptive analysis of long-term survivors (overall survival ≥5 years from surgery) treated within a multimodality therapy approach, including macroscopic complete resection. Overall survival was calculated with Kaplan-Meier analysis, and patients were matched by center and surgery year and compared with a control group of short-term survivors (<2 years) in a conditional logistic regression analysis.

RESULTS: There were 276 long-term survivors (166 men [63%]), with a median age of 59 years (range 21-83 years) at the time of diagnosis. The histology was epithelioid for 246 patients and nonepithelioid for 30 patients. The disease was on the right side in 58% of the patients. As of this analysis, 148 patients had died, 104 were alive, and 10 were lost to follow-up. Pathologic tumor stages were: pT1 (n = 50), pT2 (n = 63), pT3 (n = 90), or pT4 (n = 16) and pN0 (n = 150), pN1 (n = 20), and pN2 (n = 39). The matched control data set included 333 patients, 95 cases and 238 controls. Comparing short- with long-term survivors, we found moderate evidence that a low white blood cell count before surgery was more often observed in long-term survivors.

CONCLUSIONS: The data show that long-term survival in PM is possible in a subgroup of surgically treated patients. Histologic subtype and white blood cell count seem to be prognosticators for longer survival.}, } @article {pmid39833869, year = {2025}, author = {Ahmad, Z and Jehanzeb, H and Hussain, SN and Umar, M and Saleem, H}, title = {A synchronous occurrence of breast cancer and pleural mesothelioma: a case report.}, journal = {Journal of medical case reports}, volume = {19}, number = {1}, pages = {25}, pmid = {39833869}, issn = {1752-1947}, mesh = {Humans ; Female ; *Pleural Neoplasms/therapy/pathology/diagnosis ; Adult ; *Breast Neoplasms/pathology ; *Neoplasms, Multiple Primary/pathology ; *Mesothelioma, Malignant/pathology ; Lung Neoplasms/pathology ; Tomography, X-Ray Computed ; Paclitaxel/therapeutic use ; Mesothelioma/pathology/diagnosis ; }, abstract = {BACKGROUND: Malignant mesotheliomas are aggressive forms of tumors arising from mesothelial cells. The most common type is malignant pleural mesothelioma, which progresses rapidly and leads to pleural effusion. It typically affects older men and is strongly associated with asbestos exposure. However, a few studies have reported cases of malignant pleural mesothelioma resulting from non-asbestos factors, including radiotherapy for breast cancer, viruses, chronic inflammation, and BRCA1-associated protein-1-associated genetic mutations. Breast cancer is the most common sporadic cancer among women, and a small percentage of cases are related to genetic factors, such as BRCA1/2 and BRCA1-associated protein-1 mutations. While breast cancer can be linked with other primary malignancies through germline mutations, the synchronous occurrence of breast cancer with pleural mesothelioma is extremely rare.

CASE PRESENTATION: We present the case of a 40-year-old Pashtun woman diagnosed with primary breast cancer. She underwent surgery followed by chemotherapy (paclitaxel). During chemotherapy, she developed right-sided chest pain and dyspnea. A computed tomography scan revealed pleural thickening, and a pleural biopsy confirmed the diagnosis of malignant pleural mesothelioma, with positive results for the diagnostic markers WT1 and D240.

CONCLUSION: This case represents a rare occurrence of synchronous breast cancer and pleural mesothelioma in a 40-year-old female, and is the first case reported in Khyber Pakhtunkhwa, Pakistan. These findings demonstrate the importance of comprehensive diagnostic testing and the potential role of genetic mutations in concurrent cancers. The challenge of simultaneously treating these cancers highlights the need for further research and the importance of multidisciplinary approaches.}, } @article {pmid39831243, year = {2024}, author = {Vinci, L and Wanner, M and Karavasiloglou, N and Dressel, H and Barresi, F and Korol, D and Rohrmann, S}, title = {Incidence, mortality and survival of pleural mesothelioma in Zurich between 1981 and 2019, Switzerland.}, journal = {Journal of thoracic disease}, volume = {16}, number = {12}, pages = {8240-8249}, doi = {10.21037/jtd-24-766}, pmid = {39831243}, issn = {2072-1439}, abstract = {BACKGROUND: Pleural mesothelioma is mainly caused by (occupational) asbestos exposure. Since 1990, the import and use of asbestos is prohibited in Switzerland. However, due to the long latency time between exposure and the development of disease, incidence in Switzerland was expected to further increase for years after the ban. The aim of the present study was to analyse incidence, mortality, and survival of patients diagnosed with malignant pleural mesothelioma in the canton of Zurich in Switzerland.

METHODS: Population-based cancer registry data and cause of death statistics of the canton of Zurich from 1981 to 2019 were used to calculate age-standardized incidence and mortality rates. Time trends were investigated with joinpoint regression and net survival was computed using the Pohar-Perme method.

RESULTS: In men, the incidence rate increased from 1981 to 2002 {annual percentage change (APC) 4.7 [95% confidence interval (CI): 2.6 to 6.8]} and then decreased until 2019 [APC: -2.3 (95% CI: -4.2 to -0.3)], while in women it increased over the whole period [APC 6.2 (95% CI: -1.3 to 14.4)]. Mortality rates were stable in men and women. Three-year net survival was 9.7% (95% CI: 7.8% to 12.2%) for men and 22.1% (95% CI: 15.3% to 32.1%) for women. Men with stage I or II pleural mesothelioma had a net survival of 25.4% (95% CI: 17.2% to 37.5%) after three years whereas men with stage III or IV experienced a net survival of 7.4% (95% CI: 3.9% to 13.8%) after three years.

CONCLUSIONS: Malignant pleural mesothelioma incidence seems to have reached the peak in the canton of Zurich in men, but not yet in women. Mortality rates were stable in men and women, and net survival was poor for both sexes, particularly in men.}, } @article {pmid39831064, year = {2024}, author = {Jaurand, MC and Murphy, F and Felley-Bosco, E}, title = {Editorial: Asbestos and disease genomics: is mesothelioma a genomic paradigm?.}, journal = {Frontiers in toxicology}, volume = {6}, number = {}, pages = {1536344}, doi = {10.3389/ftox.2024.1536344}, pmid = {39831064}, issn = {2673-3080}, } @article {pmid39818191, year = {2025}, author = {Imai, H}, title = {Current drug therapy for pleural mesothelioma.}, journal = {Respiratory investigation}, volume = {63}, number = {2}, pages = {200-209}, doi = {10.1016/j.resinv.2024.12.017}, pmid = {39818191}, issn = {2212-5353}, abstract = {Pleural mesothelioma (PM) is a rare and highly aggressive malignancy originating from the pleural lining, with a median overall survival of merely 1 year. This cancer primarily arises from mesothelial cells following exposure to carcinogenic, biopersistent mineral fibers, particularly asbestos. The histological subtypes of mesothelioma are epithelioid (approximately 60%), sarcomatoid (20%), and biphasic (20%), exhibiting epithelioid and sarcomatoid characteristics. Classification is important for prognosis and guides the therapeutic strategy. Due to the typical late presentation, most patients with PM are ineligible for localized treatments such as surgery or radiotherapy. Systemic therapy, including cytotoxic chemotherapy, targeted therapies, and immunotherapy, is thus critical for managing advanced PM. For unresectable PM, decisions regarding systemic treatment are guided by patient suitability and histological characteristics. First-line therapies for advanced PM currently include the cisplatin-pemetrexed combination and the nivolumab-ipilimumab regimen. Historically, cisplatin-pemetrexed has been administered as first-line treatment, though recent advancements have introduced new therapies that significantly prolong patient survival. Innovative approaches combining immunotherapy and chemotherapy offer promising avenues for further improvement. Future treatment strategies should incorporate novel paradigms, such as combination chemo-immunotherapy, targeted agents, and potential cellular therapies, alongside companion biomarkers tailored to the histologic and molecular diversity of mesothelioma. This review explores the latest advancements in drug therapy for PM and provides an overview of current systemic treatment options.}, } @article {pmid39791266, year = {2025}, author = {Kadariya, Y and Sementino, E and Hua, X and Kappes, DJ and Testa, JR}, title = {Modeling Malignant Mesothelioma in Genetically Engineered Mice.}, journal = {Current protocols}, volume = {5}, number = {1}, pages = {e70086}, doi = {10.1002/cpz1.70086}, pmid = {39791266}, issn = {2691-1299}, mesh = {Animals ; *Mesothelioma/genetics/chemically induced/pathology ; Mice ; *Disease Models, Animal ; *Mesothelioma, Malignant/genetics/pathology ; *Lung Neoplasms/genetics/chemically induced/pathology ; Humans ; Asbestos/toxicity ; Mice, Transgenic ; Genetic Engineering ; }, abstract = {Mesothelioma is a lethal cancer of the serosal lining of the body cavities. Risk factors include environmental and genetic factors. Asbestos exposure is considered the principal environmental risk factor, but other carcinogenic mineral fibers, such as erionite, also have a causal role. Pathogenic germline (heritable) mutations of specific genes, especially BAP1, are thought to predispose the individual to mesothelioma in about 10% of cases. Somatic mutations and deletions of specific tumor suppressor genes, particularly BAP1, CDKN2A/B, and NF2, occur frequently in human mesothelioma, and asbestos-exposed mice with heterozygous deletions of any one of these genes have been shown to develop mesothelioma more often and at an accelerated rate than in control animals. Autochthonous mesothelioma mouse models, which are genetically engineered to carry multiple genetic lesions matching those observed in the human disease counterpart, closely resemble the disease phenotype and the extensive inflammatory responses that characterize human mesothelioma. Because autochthonous mice do not require asbestos exposure and form tumors rapidly, these models are invaluable for assessing novel therapeutic strategies in an immunocompetent setting. The overlapping genetic, epigenetic, and immune environments of the tumors observed in these genetically engineered mouse models (GEMMs) and human primary mesothelioma specimens support the clinical relevance of these preclinical models. This article presents protocols for studies of asbestos-induced mesothelioma in GEMMs and non-carcinogenic conditional knockout models of mesothelioma, including an example of a preclinical application. These models are invaluable for understanding the biological underpinnings of mesothelioma and for testing new therapeutics and chemoprevention or interception agents. © 2025 Wiley Periodicals LLC. Basic Protocol 1: Generation of a genetically engineered mouse model (GEMM) with a germline Bap1 knockout allele Basic Protocol 2: Generation of GEMMs with germline Bap1 knock-in alleles Basic Protocol 3: Asbestos carcinogenicity investigations with GEMMs Basic Protocol 4: Preclinical chemoprevention and chemotherapy studies using a GEMM with asbestos-induced mesothelioma Basic Protocol 5: Generation of a GEMM with conditional knockout of Bap1 Basic Protocol 6: Generation of a conditional knockout model of mesothelioma.}, } @article {pmid39776006, year = {2025}, author = {Franzoi, IG and Sauta, MD and Bonafede, M and Francioso, G and De Luca, A and Barbagli, F and Granieri, A}, title = {Psychological Distress in Patients With Asbestos-Related Diseases and Their Families: A Systematic Literature Review.}, journal = {Psycho-oncology}, volume = {34}, number = {1}, pages = {e70051}, doi = {10.1002/pon.70051}, pmid = {39776006}, issn = {1099-1611}, mesh = {Humans ; *Caregivers/psychology ; *Asbestos ; *Psychological Distress ; Quality of Life/psychology ; Mesothelioma, Malignant/psychology ; Anxiety/psychology ; Depression/psychology ; Stress, Psychological/psychology ; Occupational Exposure/adverse effects ; }, abstract = {BACKGROUND: Exposure to asbestos in the workplace is currently recognized as one of the leading causes of work-related deaths, with more than half of deaths attributable to cancer.

AIMS: The aim of this systematic literature review was to investigate the mental health and psychological distress of patients affected by asbestos-related diseases and their caregivers.

METHODS: The review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The studies were identified in October 2023 by searching four electronic databases: Scopus, Web of Science, PubMed and PsycInfo/PsycArtcicles. Risk of bias was assessed using the JBI checklist.

RESULTS: Fourteen articles were identified. The studies focused exclusively on the psychological distress of patients with malignant mesothelioma (MM) and their caregivers. MM appears to have traumatic effects on both patients and caregivers, who may experience anxiety and depression, an impoverished emotional life, somatization, social withdrawal, and a deterioration in their quality of life. In addition, a need for information about MM, its progression and associated care tasks was identified, and patients and caregivers reported frequently seeking information from online sources.

CONCLUSIONS: Our review has shown that there are still few studies addressing psychological distress in MM patients and their caregivers, and none addressing distress in the context of other asbestos-related diseases. The somatopsychic consequences of MM in patients and caregivers should encourage institutions and health professionals to develop assessment and intervention models that are tailored to the specific suffering and needs of MM patients and their caregivers and promote their residual vitality.}, } @article {pmid39773018, year = {2025}, author = {Pyana Kitenge, J and Dubbeldam, A and Said-Hartley, Q and Ronsmans, S and Jeebhay, M and Nemery, B}, title = {Asbestos-related diseases in Africa: sentinel cases of mesothelioma and asbestosis from DR Congo.}, journal = {Pulmonology}, volume = {31}, number = {1}, pages = {2449268}, doi = {10.1080/25310429.2024.2449268}, pmid = {39773018}, issn = {2531-0437}, } @article {pmid39765992, year = {2024}, author = {Ferrante, P}, title = {Respiratory Diseases with High Occupational Fraction in Italy: Results from the Italian Hospital Discharge Registry (2010-2021).}, journal = {Healthcare (Basel, Switzerland)}, volume = {12}, number = {24}, pages = {}, doi = {10.3390/healthcare12242565}, pmid = {39765992}, issn = {2227-9032}, abstract = {OBJECTIVES: Occupational respiratory diseases represent a major public health concern worldwide. This study analyses the hospitalization costs and characteristics of four major occupational respiratory diseases: malignant mesothelioma (MM), sinonasal cancer (SNC), pneumoconiosis (PN), and hypersensitivity pneumonitis (HP). The findings are situated within the context of Italy's population trends and healthcare system, offering insights into the economic and clinical burden of these diseases.

STUDY DESIGN: This retrospective, population-based study examines Italian hospitalizations for MM, SNC, PN, and HP during the period 2010-2021. The primary outcomes were the number of hospitalizations, length of stay, and associated cost. Costs were derived from charges linked to diagnosis-related groups (version 24) and major diagnostic category coding systems.

RESULTS: Though the Italian population is rapidly aging, the annual number and rate of hospitalizations declined by 35% over the study period. SNC hospitalizations aligned with the overall trend, PN and MM experienced faster declines, whereas HP admissions remained steady. MM emerged as the most resource-intensive (EUR 25 million yearly, with 86% attributable to occupation), followed by PN (EUR 10 million, entirely occupational), SNC (EUR 5 million, with EUR 650,000 occupational), and HP (EUR 2 million, with EUR 370,000 occupational). All studied diseases had an average length of stay exceeding the national one. The SNC admissions were the shortest (6.5 days) and least expensive (EUR 3647). In contrast, MM, PN, and HP had a mean length of stay exceeding 10 days, with admission costs averaging EUR 4700 for MM and EUR 4000 for PN and HP. The median age was the highest for PN (78 years) and MM (71 years), while SNC and HP patients had a median age of approximately 65 years.

CONCLUSIONS: Consistent with their anticipated benefits, Italian workplace health regulations over the last three decades, including the 1992 asbestos ban and D.lgs. 81/2008, are associated with significant reductions in the hospitalization burden and an increased median age at discharge for MM and PN. In contrast, fewer conclusions can be drawn for SNC and HP due to their lower occupational fractions (10-20%). This finding suggests adding an occupational exposure flag in hospital records for acknowledged occupational diseases to enhance surveillance. Finally, this study provides the first estimate of the occupational fraction of hospitalization costs for the studied diseases in Italy.}, } @article {pmid39758284, year = {2025}, author = {Bertolotti, M and Tamburro, M and Salzo, A and Cassinari, A and Crivellari, S and Bertolina, C and Farotto, M and Adesso, C and Di Palma, MA and Natale, A and Torregiani, F and Pacileo, G and Maconi, A and Ripabelli, G}, title = {Knowledge and awareness of asbestos risk among General Practitioners: Validation of a questionnaire in an area with a high incidence of asbestos-related diseases.}, journal = {Preventive medicine reports}, volume = {49}, number = {}, pages = {102940}, pmid = {39758284}, issn = {2211-3355}, abstract = {OBJECTIVE: Given the critical role of general practitioners (GPs) in the early diagnosis and management of asbestos-related diseases (ARDs), and the significant history of asbestos fibres pollution in Alessandria Local Health Authority (ASL AL), this project aimed to assess the knowledge and awareness of asbestos risks, as well as the experience in diagnosing ARDs among GPs working in Alessandria province, Northern Italy.

METHODS: A questionnaire was administered to 216 GPs from all ASL AL territorial districts during 26 Territorial Assistance Equipes (EATs) meetings, held from September 2022 to January 2023. It contained 29 questions covering three main areas: 'knowledge and awareness', 'competence and experience', 'sociodemographic characteristics and workload'.

RESULTS: Although GPs were aware of the health hazards of asbestos (94 %) and the increased risk of mesothelioma from asbestos exposure (92.6 %), significant disparities and heterogeneity of knowledge were observed among territorial districts and by comparing Casale Monferrato district with all the others, particularly regarding asbestos exposure routes, reporting of occupational diseases, and mesothelioma latency.

CONCLUSIONS: This project provides a comprehensive overview of GPs' knowledge, awareness and experience in managing ARDs, providing indications of customised training requirements. This evaluation could be extended to all areas with a history of previous asbestos exposure and provide a useful tool for policy makers to define and plan strategic actions on asbestos. This work could also be adapted to different realities with a history of environmental pollutant exposure other than asbestos, which pose a risk for the development of several diseases.}, } @article {pmid39751851, year = {2025}, author = {D'Alonzo, RA and Keam, S and Gill, S and Rowshanfarzad, P and Nowak, AK and Ebert, MA and Cook, AM}, title = {Fractionated low-dose radiotherapy primes the tumor microenvironment for immunotherapy in a murine mesothelioma model.}, journal = {Cancer immunology, immunotherapy : CII}, volume = {74}, number = {2}, pages = {44}, pmid = {39751851}, issn = {1432-0851}, support = {APP1197652//National Health & Medical Research Council with a Centre of Research Excellence/ ; APP1197652//National Health & Medical Research Council with a Centre of Research Excellence/ ; APP1197652//National Health & Medical Research Council with a Centre of Research Excellence/ ; 1163065//Cancer Australia Priority-driven Collaborative Cancer Research Scheme/ ; 1163065//Cancer Australia Priority-driven Collaborative Cancer Research Scheme/ ; }, mesh = {Animals ; Mice ; *Tumor Microenvironment/immunology/radiation effects ; *Immunotherapy/methods ; *Mesothelioma/radiotherapy/immunology/therapy/pathology ; *Disease Models, Animal ; Dose Fractionation, Radiation ; Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; Female ; Mice, Inbred C57BL ; Humans ; Cell Line, Tumor ; Combined Modality Therapy/methods ; }, abstract = {Combination immune checkpoint inhibitors (nivolumab and ipilimumab) are currently a first-line treatment for mesothelioma; however, not all patients respond. The efficacy of treatment is influenced by the tumor microenvironment. Murine mesothelioma tumors were irritated with various radiotherapy doses. Radiotherapy induced vasculature changes were monitored by power Doppler and photoacoustic ultrasound and analyzed via mixed-effects models. Tissue staining was used to investigate the immune cell infiltrate of tumors. The optimal radiotherapy schedule was combined with immune checkpoint inhibitors, and the survival of mice was analyzed. Using low-dose, low-fraction radiotherapy allowed favorable modification of the murine mesothelioma tumor microenvironment. Irradiating tumors with 2 Gy × 5 fractions significantly improved blood flow and reduced hypoxia, consequently increasing the presence of CD8[+] and regulatory T cells in the tumor. Understanding the transient nature of these changes is crucial for optimizing the timing of therapeutic delivery. The combination of radiotherapy with dual immunotherapy (anti-PD-1 plus anti-CTLA-4) proved highly curative when administered concurrently. A diminishing rate of cures was noted with an increasing delay between radiotherapy and subsequent immunotherapy. Concurrent low-dose, low-fraction radiotherapy emerges as a translatable approach for improving the efficacy of immune checkpoint inhibitors in patients.}, } @article {pmid39747518, year = {2025}, author = {Nielsen, DM and Hsu, M and Zapata, M and Ciavarra, G and van Zyl, L}, title = {Bayesian analysis of the rate of spontaneous malignant mesothelioma among BAP1 mutant mice in the absence of asbestos exposure.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {169}, pmid = {39747518}, issn = {2045-2322}, abstract = {Cancers of the mesothelium, such as malignant mesothelioma (MM), historically have been attributed solely to exposure to asbestos. Recent large scale genetic and genomic functional studies now show that approximately 20% of all human mesotheliomas are causally linked to highly penetrant inherited (germline) pathogenic mutations in numerous cancer related genes. The rarity of these mutations in humans makes it difficult to perform statistically conclusive genetic studies to understand their biological effects. This has created a disconnect between functional and epidemiological studies. However, since the molecular pathogenesis of MM in mice accurately recapitulates that of human disease, this disconnect between functional and epidemiological studies can be overcome by using inbred mouse strains that harbor mutation(s) in genes involved in the disease. Most mouse studies have focused on the effect of asbestos exposure, leaving the effects of genetic mutations in the absence of exposure understudied. Here, using existing peer-reviewed studies, we investigate the rate of spontaneous MM among mice with and without germline genetic mutations, in the absence of asbestos exposure. We leveraged these published data to generate a historical control dataset (HCD) to allow us to improve statistical power and account for genetic heterogeneity between studies. Our Bayesian analyses indicate that the odds of spontaneous MM among germline BAP1 mutant mice is substantially larger than that of wildtype mice. These results support the existing biological study findings that mesotheliomas can arise in the presence of pathogenic germline mutations, independently of asbestos exposure.}, } @article {pmid39737233, year = {2024}, author = {Franzoi, IG}, title = {Rediscovering one's own voice in a brief psychoanalytic group intervention aimed at malignant mesothelioma patients and their families.}, journal = {Frontiers in psychology}, volume = {15}, number = {}, pages = {1471057}, pmid = {39737233}, issn = {1664-1078}, abstract = {Occupational and/or environmental exposure to asbestos can lead to clinical manifestation of a variety of diseases, including malignant mesothelioma (MM), a rare cancer with a particularly high incidence rate in areas with a long history of asbestos processing. This paper aims to describe brief psychoanalytic groups (BPGs), which is an intervention model aimed at MM patients and their families in the early stages of the disease, shortly after diagnosis. The BPG model comprises 12 weekly sessions of 1 h each, co-led by two psychoanalytically oriented psychotherapists who are trained in working with cancer patients and their families and in the specifics of the BPG setting. Reflections in this paper on the BPGs will attempt to trace the voice of the group in clinical material, paying attention to its horizontal unfolding as a melodic development over time and its vertical unfolding as a harmonic interweaving between the different individual voices, which, even when opposed to each other, can find a generative interlocking of meaning. In the BPG, then, it is possible to set in motion transformations that allow one to embrace the different and diverse affective colorations of experience, evolve toward a thinking that is capable of incorporating intense emotions related to death and grief, follow healthier paths of interaction on an intrapsychic and interpersonal level, and find traces of one's own vitality.}, } @article {pmid39731918, year = {2024}, author = {Chin, WL and Cook, AM and Chee, J and Principe, N and Hoang, TS and Kidman, J and Hmon, KPW and Yeow, Y and Jones, ME and Hou, R and Denisenko, E and McDonnell, AM and Hon, CC and Moody, J and Anderson, D and Yip, S and Cummins, MM and Stockler, MR and Kok, PS and Brown, C and John, T and Kao, SC and Karikios, DJ and O'Byrne, KJ and Hughes, BGM and Lake, RA and Forrest, ARR and Nowak, AK and Lassmann, T and Lesterhuis, WJ}, title = {Coupling of response biomarkers between tumor and peripheral blood in patients undergoing chemoimmunotherapy.}, journal = {Cell reports. Medicine}, volume = {}, number = {}, pages = {101882}, doi = {10.1016/j.xcrm.2024.101882}, pmid = {39731918}, issn = {2666-3791}, abstract = {Platinum-based chemotherapy in combination with anti-PD-L1 antibodies has shown promising results in mesothelioma. However, the immunological mechanisms underlying its efficacy are not well understood and there are no predictive biomarkers to guide treatment decisions. Here, we combine time course RNA sequencing (RNA-seq) of peripheral blood mononuclear cells with pre-treatment tumor transcriptome data from the single-arm, phase 2 DREAM trial (N = 54). Single-cell RNA-seq and T cell receptor sequencing (TCR-seq) reveal that CD8[+] T effector memory (TEM) cells with stem-like properties are more abundant in peripheral blood of responders and that this population expands upon treatment. These peripheral blood changes are linked to the transcriptional state of the tumor microenvironment. Combining information from both compartments, rather than individually, is most predictive of response. Our study highlights complex interactions between the tumor and immune cells in peripheral blood during objective tumor responses to chemoimmunotherapy. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12616001170415.}, } @article {pmid39697085, year = {2024}, author = {Kurzhunbaeva, Z and Dzhusupov, K and Spinazzè, A and Visonà, SD and Sulaimanova, C and Kasymov, O and Belluso, E and Colosio, C}, title = {Human Exposure to Asbestos in Central Asian Countries and Health Effects: A Narrative Review.}, journal = {La Medicina del lavoro}, volume = {115}, number = {6}, pages = {e2024042}, doi = {10.23749/mdl.v115i6.15453}, pmid = {39697085}, issn = {0025-7818}, mesh = {Humans ; *Asbestos/adverse effects ; Environmental Exposure/adverse effects ; Occupational Exposure/adverse effects ; Asia, Central/epidemiology ; Asbestosis/epidemiology/etiology ; Kazakhstan/epidemiology ; Mesothelioma/etiology/epidemiology ; }, abstract = {The discovery of the detrimental effects of asbestos on human health came long after its widespread use, with the first scientific evidence of asbestos-related diseases emerging in the late 19th and early 20th centuries. Despite efforts to ban its use, asbestos continues to be mined and used in Central Asia (as well as in Russia, China, and other countries). To gain a deeper understanding of the situation in Central Asia, we have conducted a systematic review of scientific literature on the use of asbestos, exposure assessment, and health consequences of asbestos exposure in this geographic area. This review encompasses studies about exposure assessments, epidemiological data, and biochemical or clinical surveys conducted in Kazakhstan, Uzbekistan, Tajikistan, Turkmenistan, and Kyrgyzstan. A total of 18 articles met the inclusion criteria, and their content is summarised in this review, which represents the first attempt to systematically examine research on asbestos and its impact on the health of workers and the general population in Central Asia countries, including literature published in Russian and English. The findings here highlighted the substantial limitations of the currently available knowledge about the impact of asbestos on health in this geographical area.}, } @article {pmid39686704, year = {2024}, author = {Meisenkothen, C}, title = {Underestimation of Chrysotile Health Risk due to Under-ascertainment of Mesothelioma: Evidence from a Century of Connecticut's Experience with the "Magic Mineral".}, journal = {New solutions : a journal of environmental and occupational health policy : NS}, volume = {}, number = {}, pages = {10482911241303469}, doi = {10.1177/10482911241303469}, pmid = {39686704}, issn = {1541-3772}, abstract = {Over a century ago, Connecticut industry began using chrysotile asbestos. Chrysotile found a home in several factories that used it exclusively or predominantly. The occurrence of mesothelioma in 4 of those factories is the subject of this paper-2 have been reported previously and are updated here with new information; one was the subject of a prior internal corporate study that was never published; one is reported here for the first time. Twenty-four cases of mesothelioma have been identified among these workers, including several who had no known amphibole exposure. It is likely that additional cases of mesothelioma have been missed. The full scale of the hazard may never be completely known, but reports such as the present one add to the weight of evidence that chrysotile causes mesothelioma in humans and that the full extent of the epidemic is probably wider than retrospective studies have revealed. Continued vigilance is required.}, } @article {pmid39682143, year = {2024}, author = {Stella, S and Ceresoli, GL and Dallari, B and Barile, R and Maisenti, F and Rugarli, S and Marinaccio, A and Consonni, D and Mensi, C}, title = {Mesothelioma of the Tunica Vaginalis Testis: Diagnostic and Therapeutic Management. A Comprehensive Review, 1982-2024.}, journal = {Cancers}, volume = {16}, number = {23}, pages = {}, doi = {10.3390/cancers16233956}, pmid = {39682143}, issn = {2072-6694}, support = {BRIC INAIL ID 66/2022 [Grant PB-0184]//INAIL: Istituto Nazionale per l'Assicurazione contro gli Infortuni sul Lavoro/ ; }, abstract = {BACKGROUND: Mesothelioma of the tunica vaginalis testis (MTVT) is an extremely rare and aggressive cancer. The diagnosis and management of MTVT is complex, and no standard treatment protocol is available.

METHODS: We conducted a systematic literature review from 1 January 1982 to 14 March 2024 using PubMed to collect all the available case reports and case series. A descriptive analysis of patient characteristics with clinical presentation, diagnostic work-up, therapeutic management, and past asbestos exposure was performed. Survival times of patients treated with different therapeutic approaches were evaluated.

RESULTS: Overall, 289 patients with MTVT were included in our analysis. The most common clinical presentations were scrotal/testicular swelling or mass (187 patients, 65%) and the presence of hydrocele (159, 55%). Imaging evaluation, mostly with ultrasonography or CT scan, was reported in two-thirds of cases. Radical surgery (216 patients, 75%) with orchiectomy and, in select cases, hemiscrotectomy and inguinal lymphadenectomy was the most frequent therapeutic approach. A minority of patients (49, 17%) received adjuvant therapy after surgery (radiotherapy, chemotherapy, or a combination of the two), with no evidence of survival improvement.

CONCLUSIONS: No standard guidelines for MTVT are available so far. Radical surgery following accurate radiological staging should be the mainstay of treatment. The role of adjuvant treatments remains undefined. Due to its rarity, MTVT should be treated in referral centers, and patients' data should be collected in a dedicated register in order to improve the knowledge of this exceedingly rare disease and establish optimal diagnostic and therapeutic management.}, } @article {pmid39679483, year = {2024}, author = {Taiano, L and Porzio, A and Massari, S and Iavicoli, I and Palladino, R and Menegozzo, S and Mensi, C and Binazzi, A and Menegozzo, M and Marinaccio, A}, title = {[Mortality due to mesothelioma and asbestosis in Campania Region (Southern Italy): perspectives for reducing asbestos exposure].}, journal = {Epidemiologia e prevenzione}, volume = {48}, number = {6}, pages = {429-437}, doi = {10.19191/EP24.6.A754.134}, pmid = {39679483}, issn = {1120-9763}, mesh = {Humans ; Italy/epidemiology ; *Asbestosis/mortality ; Female ; Male ; *Mesothelioma/mortality ; *Asbestos/adverse effects ; Aged ; Middle Aged ; Environmental Exposure/adverse effects ; Lung Neoplasms/mortality ; Aged, 80 and over ; Adult ; }, abstract = {OBJECTIVES: to provide an overview of the geographical distribution of mesothelioma and asbestosis deaths in the Campania Region (Southern Italy) occurred from 2005 to 2018 and to identify areas at higher risk.

DESIGN: for each municipality, Standardized Mortality Ratios (SMRs) for mesothelioma and asbestosis have been estimated from the mortality data provided by the Italian National Institute of Statistics (Istat). Deaths for which mesothelioma and asbestosis were identified as the underlying causes, according to the classification system ICD-10 codes (C45 and J61, respectively), were included. Expected cases were estimated applying age- and gender-specific mortality rates in Campania on resident populations of each municipality. Furthermore, the association between the municipal SMR and the local socioeconomic deprivation index based on the 2011 General Census of Population and Housing was also analysed.

SETTING AND PARTICIPANTS: Campania Region.

MAIN OUTCOMES MEASURES: the study outcomes were standardized mortality ratios for mesothelioma and asbestosis and the identification of territorial subareas.

RESULTS: a total of 998 deaths attributed to mesothelioma and 62 to asbestosis were identified. No cases of death due to mesothelioma or asbestosis were reported in the province of Benevento. A significant increase in mortality due to mesothelioma was observed across 34 municipalities. These findings show that several municipalities within the province of Naples display a high increase in mortality due to mesothelioma and asbestosis, with 506 deaths in total and 246 cases recorded in the municipality of Naples against 178,37 expected (SMR 1,38; 90%CI 1.24-1.53). In 15 municipalities, a notable increase in mortality for asbestosis was recorded; in Naples, 28 cases occurred (SMR 2,51; 90%CI 1.84-3.42). The overlap between mortality maps for mesothelioma and asbestosis confirms the existence of areas subjected to definite and prolonged asbestos exposure. Additionally, a correlation with the deprivation index was noted: the pooled SMR by quintiles increases with higher quintiles of the deprivation index, for both mesothelioma and asbestosis.

CONCLUSIONS: results highlight the crucial need for epidemiological surveillance of asbestos-related diseases in Campania. Actively searching out for new cases of mesothelioma in the entire region is a crucial task in primary prevention of occupational, environmental, and domestic exposures to asbestos.}, } @article {pmid39668371, year = {2024}, author = {Tibaldi, E and Gnudi, F and Mandrioli, D and Bruno, C and Zona, A and Fazzo, L and Comba, P}, title = {Pathological characterization of lung fibrosis in Sprague-Dawley rats treated with fluoro-edenite fibres by intrapleural injection.}, journal = {Journal of occupational medicine and toxicology (London, England)}, volume = {19}, number = {1}, pages = {45}, pmid = {39668371}, issn = {1745-6673}, abstract = {BACKGROUND: An increased incidence of pleural mesotheliomas in Biancavilla (Italy) was attributed to the environmental exposure to fluoro-edenite (FE). Results from the Ramazzini Institute (RI) in vivo long-term study confirmed the evidence that exposure to FE fibres is correlated with an increase of malignant pleural mesotheliomas in Sprague-Dawley rats. Recently asbestosis-like features were substantiated in Biancavilla residents without known occupational exposures. Aim of this work was to establish whether FE induce lung fibrosis with a pathogenetic mechanism similar to other asbestiform fibres.

METHODS: Original slides from the RI study were systematically re-examined to characterize the FE-induced lesions. Quantitative analysis of lung fibrosis was assessed following the Ashcroft method. Immunohistochemical analysis of protein involved in fibrotic responses and histochemical staining for FE-fibres identification were performed.

RESULTS: Like asbestos, FE caused fibrotic lesions, pleural plaques or nodules and mesotheliomas. A significant increase of lung fibrosis (p < 0.001) was observed in the FE-treated groups compared to untreated controls. In the fibrotic responses to FE, vimentin was the most expressed protein, followed by collagen-I and alpha-SMA. Finally, ferruginous bodies, characterized by iron deposits and ferritin expression, were observed in FE-induced lesions.

CONCLUSIONS: This study confirmed that FE exposure promotes the onset of fibrotic lesions at pleural level, as fibrous plaques or nodules and fibrosis, through a mechanism similar to other form of asbestos. These results combined with epidemiological study reported in Biancavilla residents, corroborate the need to promote health and epidemiological surveillance plans of respiratory diseases in population living in FE contaminated sites.}, } @article {pmid39611075, year = {2024}, author = {Fadl, L and Fadl, M and Fadl, O and Thaplar G Gouda, SG and Mirza, H}, title = {A Case Report of Peritoneal Mesothelioma as an Acute Abdomen Mimic: A Rare Presentation and Diagnostic Challenges.}, journal = {Cureus}, volume = {16}, number = {11}, pages = {e74598}, pmid = {39611075}, issn = {2168-8184}, abstract = {Malignant peritoneal mesothelioma (MPM) is a rare and aggressive cancer often linked to asbestos exposure. This case report presents a 60-year-old man with a history of asbestos exposure who developed MPM, initially presenting with acute abdominal pain, an uncommon mimic of the acute abdomen. Diagnosing MPM is challenging due to its vague symptoms, often leading to delayed diagnosis. Additionally, the patient developed internal jugular vein thrombosis, a rare complication associated with malignancies. This case highlights the rare presentation of peritoneal mesothelioma as an acute abdomen mimic, the diagnostic complexities associated with MPM, and the rare type of thromboembolic event in this case.}, } @article {pmid39609252, year = {2024}, author = {Visonà, SD and Untalan, M and Bertoglio, B and Capella, S and Belluso, E and Billò, M and Ivic-Pavlicic, T and Taioli, E}, title = {Asbestos Burden in Lungs of Subjects Deceased From Mesothelioma Who Lived in Proximity to an Asbestos Factory: A Topographic Post-Mortem SEM-EDS Study.}, journal = {American journal of industrial medicine}, volume = {}, number = {}, pages = {}, doi = {10.1002/ajim.23680}, pmid = {39609252}, issn = {1097-0274}, support = {//The authors received no specific funding for this work./ ; }, abstract = {BACKGROUND: Asbestos exposure and its pathological consequences, especially malignant mesothelioma (MM) still represent a major public health problem on a global scale. After the ban of asbestos in most western countries, nonoccupational exposure plays an essential role in MM pathogenesis. However, few studies have quantified asbestos lung burden after environmental exposure. The main objective of this work is to understand if asbestos lung content is different between occupationally and environmentally exposed individuals, and if the distance between the subjects' residences and the source of exposure is significantly associated with the asbestos lung burden.

METHODS: In this retrospective, observational study we quantified, with analytical scanning electron microscopy, asbestos content in lungs of individuals deceased from MM between 2005 and 2019, who were exposed to asbestos (occupationally and/or environmentally) in Broni, a small town in northern Italy where an important asbestos-cement plant operated until 1993.

RESULTS: We analyzed asbestos lung content of 77 subjects. We found that the asbestos lung content in MM patients who lived around the asbestos factory was as high as that seen in occupationally exposed individuals; this holds true in residents up to 10 km radius from the factory. We found no significant associations between the residence duration/distance ratio and asbestos lung burden.

CONCLUSIONS: This study suggests that heavy asbestos pollution involves not only the area adjacent to the factory, but the entire town of Broni and the surroundings. This is alarming if we consider that most asbestos factories still active in some countries are located close to towns and dwellings.}, } @article {pmid39607779, year = {2024}, author = {Faccioli, E and Dell'Amore, A and Lorenzoni, G and Schiavon, M and Canu, G and Pasello, G and Zambello, G and Sepulcri, M and Sambataro, V and Labella, F and Giraudo, C and Gregori, D and Calabrese, F and Rea, F}, title = {Surgery for pleural mesothelioma in multimodality setting: comparison between surgical techniques in a high-volume center.}, journal = {European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery}, volume = {}, number = {}, pages = {}, doi = {10.1093/ejcts/ezae431}, pmid = {39607779}, issn = {1873-734X}, abstract = {OBJECTIVES: Pleural mesothelioma (PM) is an aggressive disease linked to asbestos exposure, presenting significant treatment challenges. The recommended approach is multimodal treatment, even if the concept of resectable PM and the superiority of one surgical technique over the other [(extended) pleurectomy decortication [(E)PD] vs extra-pleural pneumonectomy (EPP)] are matter of debates. The aim of this study is to compare the two techniques in terms of short- and long-term outcomes at a high-volume center.

METHODS: Clinical data from PM patients who underwent radical surgery [(E)PD and EPP] between 1994 and 2022 were collected. A propensity score weighting approach was used for non-random intervention allocation. Survival distribution was estimated using Kaplan-Meier method and the association with outcomes was evaluated using a weighted Cox Proportional Hazard Models.

RESULTS: Among 254 patients, 125 (49%) underwent EPP and 129 (51%) (E)PD. The 90-day mortality was higher in the EPP group (7.2% vs 0%; p = 0.01). No difference in 1-,3- and 5-year survival was found: 65.8%, 26%, 17% for EPP and 75.5%, 39.7% and 21.3% for (E)PD; p = 0.39). The multivariable weighted Cox model identified no increased risk of death (HR 1.25; p = 0.49) or recurrence (HR 1.05; p = 0.858) in the EPP group. Pre-operative total lung capacity (TLC) was significantly associated with a reduced risk of death (HR 0.96; p = 0.023) and recurrence (HR 0.97; p = 0.019) at follow-up while preoperative disease burden to a higher risk of recurrence (HR 1.01; p = 0.02).

CONCLUSIONS: Our experience showed acceptable short- and long-term outcomes in both procedures, making EPP still an option only for carefully selected patients at high volume center. Surgery, although recently debated, should be performed exclusively in expert centers to minimize post-operative risks. The identification of new prognostic factors is crucial for better selecting patients who may benefit from surgery within the context of multimodal treatment.}, } @article {pmid39604235, year = {2024}, author = {Chen, YQ and Gao, ZB and Shen, W and Ying, SB and He, XL and Zhang, X and Jiang, ZQ and Lou, JL}, title = {[The prognostic value of BAP1 protein loss in patients with malignant mesothelioma].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {42}, number = {11}, pages = {815-820}, doi = {10.3760/cma.j.cn121094-20240112-00016}, pmid = {39604235}, issn = {1001-9391}, support = {KYYB202113//The Basic Scientific Research Business Fee and Basic Scientific Research Plan of Hangzhou Medical College/ ; 81973011//The National Natural Science Foundation of China/ ; //The Key Discipline of Zhejiang Province in Public Health and Preventive Medicine (First Class, Category A) of Hangzhou Medical College/ ; }, mesh = {Humans ; *Ubiquitin Thiolesterase/metabolism ; Female ; *Tumor Suppressor Proteins/metabolism ; Male ; Middle Aged ; *Mesothelioma, Malignant/metabolism ; Prognosis ; *Lung Neoplasms/metabolism ; Aged ; *Mesothelioma/metabolism ; Survival Rate ; Kaplan-Meier Estimate ; Proportional Hazards Models ; Adult ; }, abstract = {Objective: To explore the prognostic value of BRCA1-associated protein 1 (BAP1) expression loss in patients with malignant mesothelioma (MM) . Methods: A total of 82 MM patients from January 1998 to December 2017 in Zhejiang Province were selected to detect the expression of BAP1 protein by immunohistochemical analysis. Kaplan-Meier method was used to draw the survival curve, and multivariate Cox proportional risk model was used to analyze the factors affecting the survival rate. Results: Among 82 MM patients, 61 (74.4%) were female, aged (57±11) years. BAP1 protein expression was deficient in 39 patients (47.6%). The survival rate was correlated with the loss of BAP1 protein expression and age (χ(2)=5.27, 5.66, P=0.022, 0.017). Subgroup analysis showed that loss of BAP1 protein expression was associated with better prognosis in MM patients <57 years of age, female, pleural MM, epithelial MM, and treated with drugs or surgery (P<0.05). Multivariate model results showed that positive expression of BAP1 protein (HR=3.75, 95%CI: 2.23-6.30, P<0.001) and age ≥57 years (HR=1.66, 95% CI: 1.01-2.72, P=0.049) were risk factors for survival in patients with MM. Conclusion: Loss of BAP1 protein expression may be an independent prognostic factor in patients with MM, which is associated with longer survival.}, } @article {pmid39569577, year = {2024}, author = {Angelini, A and Martini, A and Masala, G}, title = {[Update. Inventory of occupational exposure to asbestos with particular reference to Tuscan worker].}, journal = {Epidemiologia e prevenzione}, volume = {48}, number = {6}, pages = {1-128}, doi = {10.19191/EP24.6.S1.128}, pmid = {39569577}, issn = {1120-9763}, mesh = {Italy/epidemiology ; *Asbestos/adverse effects ; Humans ; *Occupational Exposure/adverse effects ; Occupational Diseases/epidemiology ; Lung Neoplasms/epidemiology/etiology/chemically induced ; Asbestosis/epidemiology/etiology ; Mesothelioma/epidemiology/etiology ; Carcinogens ; Population Surveillance ; }, abstract = {This Catalogue is a collection of information on the use of raw asbestos and asbestos-containing materials used in several industries and occupational activities, with particular attention to the situation of Tuscany, a region of Central Italy. The work was developed at the Institute for Cancer Research, Prevention and Clinical Network (ISPRO) of Florence, where epidemiologic research and surveillance activities have been developing since 1988 and where the coordination and evaluation of the regional health surveillance programme provided to past asbestos workers started in 2016 and is still ongoing. The Catalogue aims at being a working tool for all health professionals engaged in examining and classifying the occupational asbestos exposures of subjects both affected by diseases that could be associated to this carcinogen and examined within the regional health surveillance programme. It is necessary for the health personnel engaged in the above-mentioned activities to know or to have the possibility to find exact and detailed data on asbestos exposure by occupational sector. These data are briefly described in the 29 factsheets this Catalogue consists of. In each factsheet, the presence and every use of asbestos are described, with reference to a precise occupational sector. Several occupational sectors can be considered together because of analogies on asbestos exposure. Occupations are considered on the basis of existing evidence on the use of raw asbestos or asbestos-containing materials (as semi-finished or finished products or as auxiliary materials in production processes). Besides the presence and use of asbestos, a description of the possible exposures of workers is reported. Sources of information were scientific and grey literature as well as the 8,097 occupational histories of mesothelioma registered by the specific Tuscan registry. Some factsheets have been revised and enhanced by Italian experts on the asbestos exposure with a specific competence in the examined sectors. Each factsheet includes also questions to be addressed to workers in order to examine in depth their possible asbestos exposure. For those who would like to expand their knowledge on this topic, references are reported both at the end of each factsheet and at the end of the volume. In all industrialized countries, also in those which have not already banned asbestos use, a decrease in the use of this material and in the relative exposure have been observing since the end of the Seventies, few years after the general consensus within the scientific community on asbestos carcinogenicity. This decreasing trend has been becoming greater and greater since the end of the Eighties, when more restrictive regulations have been approved and applied, especially in occupational settings. Nevertheless, nowadays asbestos-related diseases are still diagnosed due to past exposures, although during next decade a decreasing incidence of malignant mesothelioma - the cancer most specifically related to this carcinogen and characterized by a very bad prognosis and the longest latency - could be observed. Particular attention will be paid to jobs regarding renovation of old buildings containing asbestos and to decontamination activities. In conclusion, this Catalogue is a working tool - although it is not exhaustive and could be upgraded with new information - for all professionals engaged in asbestos risk prevention activities as health personnel, personnel of insurance companies, employers, and employee representatives.}, } @article {pmid39568634, year = {2024}, author = {Yilmaz, ME and Rashidfarokhi, M and Pollard, K and Durmus, N and Keserci, S and Sterman, DH and Arslan, AA and Shao, Y and Reibman, J}, title = {Mesothelioma Cases in the World Trade Center Survivors.}, journal = {Annals of case reports}, volume = {9}, number = {2}, pages = {}, pmid = {39568634}, issn = {2574-7754}, abstract = {OBJECTIVES: The destruction of the World Trade Center (WTC) towers in New York City on September 11, 2001 (9/11), released approximately 1 million tons of pulverized particulate matter throughout southern Manhattan and areas in Brooklyn, exposing community members and responders to high levels of potentially toxic environmental particles. Asbestos exposure was a health concern because of its use in certain sections of the WTC towers. Malignant mesothelioma, originating from the lining cells (mesothelium) of the peritoneal and pleural cavities, is one complication associated with asbestos exposure.

METHODS: The WTC Environmental Health Center (WTC EHC) is a treatment and surveillance program for community members (Survivors) exposed to WTC dust and fumes.

RESULTS: In this report, we describe four cases of mesothelioma in the WTC EHC as of July 1st, 2023. Two of our patients have been diagnosed with peritoneal mesothelioma and two patients have been diagnosed with pleural mesothelioma.

CONCLUSION: Given the known delay in the development of mesotheliomas after asbestos exposure, we provide information on these early mesothelioma cases to enhance the understanding of the adverse health effects of WTC exposures on the local community.}, } @article {pmid39558529, year = {2024}, author = {Willis, VJ and Levin, JL and Nessim, DE}, title = {A Review of Job Assignments and Asbestos Workplace Exposure Measurements for TAWP Mesothelioma Deaths Through 2011.}, journal = {American journal of industrial medicine}, volume = {}, number = {}, pages = {}, doi = {10.1002/ajim.23675}, pmid = {39558529}, issn = {1097-0274}, support = {//This study was supported by the Jesse Jones Distinguished Professorship of Occupational Health Sciences Endowment, University of Texas at Tyler Health Science Center Occupational and Environmental Medicine Residency Program./ ; }, abstract = {INTRODUCTION: Asbestos workers have a higher risk of developing mesothelioma; however, few studies have looked at specific jobs and job locations within asbestos factories. The purpose of this study was to investigate asbestos exposure in different job locations of the Tyler, Texas asbestos plant to determine if there was a relationship between the duration of exposure and air fiber concentration burden in workers who developed pleural versus peritoneal mesothelioma.

METHODS: This study used a patient information database to compile secondary data on 23 workers who died from mesothelioma through 2011. The airborne fiber exposure burdens for each of the 23 workers were estimated and then stratified by job location category and by type of mesothelioma for analysis.

RESULTS: Most of the worker cases were assigned to the forming area which had the overall highest fiber concentration of all the plant's job locations. Workers who developed pleural mesothelioma spent the most time in the packing and miscellaneous locations, whereas workers who developed peritoneal mesothelioma worked mostly in the forming and miscellaneous locations. There were significant differences in days worked and estimated airborne exposure fiber burden between the pleural and peritoneal mesothelioma cases in the forming and curing locations.

CONCLUSION: Results from this study reiterate the association between occupational asbestos exposure and mesothelioma, emphasizing the importance of concentration of respirable asbestos dust levels and duration of exposure.}, } @article {pmid39539262, year = {2024}, author = {Ebrahimi, A and Ak, G and Özel, C and İzgördü, H and Ghorbanpoor, H and Hassan, S and Avci, H and Metintaş, M}, title = {Clinical Perspectives and Novel Preclinical Models of Malignant Pleural Mesothelioma: A Critical Review.}, journal = {ACS pharmacology & translational science}, volume = {7}, number = {11}, pages = {3299-3333}, doi = {10.1021/acsptsci.4c00324}, pmid = {39539262}, issn = {2575-9108}, abstract = {Pleural mesothelioma (PM), a rare malignant tumor explicitly associated with asbestos and erionite exposures, has become a global health problem due to limited treatment options and a poor prognosis, in which the median life expectancy varies depending on the method of treatment. However, the importance of early diagnosis is emphasized, and the practical methods have not matured yet. This study provides a critical overview of PM, addressing various aspects like epidemiology, etiology, diagnosis, treatment options, and the potential use of advanced technologies like microfluidic chip-based models for research and diagnosis. It initially begins with fundamentals of clinical aspects and then discusses the identification of disease-specific biomarkers in patients' serum or plasma samples, which could potentially be used for early diagnosis. A detailed investigation of the sophisticated preclinical models is highlighted. Recent three-dimensional (3D) model accomplishments, including microarchitecture modeling by transwell coculture, spheroids, organoids, 3D bioprinting constructs, and ex vivo tumor slices, are discussed comprehensively. On-chip models that imitate physiological processes, such as detection chips and therapeutic screening chips, are assessed as potential techniques. The review concludes with a critical and constructive discussion of the growing interest in the topic and its limitations and suggestions.}, } @article {pmid39534944, year = {2024}, author = {Wu, Y and Zhao, Y and Yu, L and Wang, R and Feng, W and Wu, Y and Wang, L and Chen, H and He, Z and Wang, Q}, title = {Case report: targeted therapy of malignant pleural mesothelioma with anaplastic lymphoma kinase receptor tyrosine kinase gene fusion mutation by crizotinib.}, journal = {The Journal of international medical research}, volume = {52}, number = {11}, pages = {3000605241287320}, doi = {10.1177/03000605241287320}, pmid = {39534944}, issn = {1473-2300}, mesh = {Humans ; *Crizotinib/therapeutic use ; Female ; *Anaplastic Lymphoma Kinase/genetics ; *Mesothelioma, Malignant/drug therapy/genetics/pathology ; *Mutation ; *Lung Neoplasms/genetics/drug therapy/pathology ; *Pleural Neoplasms/genetics/drug therapy/pathology ; *Protein Kinase Inhibitors/therapeutic use ; *Mesothelioma/genetics/drug therapy/pathology ; Pyridines/therapeutic use ; Receptor Protein-Tyrosine Kinases/genetics ; Pyrazoles/therapeutic use ; Molecular Targeted Therapy ; Middle Aged ; Gene Fusion ; }, abstract = {Malignant mesothelioma is a rare highly invasive tumour originating from the mesothelial cells of the pleura, peritoneum and pericardium. Malignant pleural mesothelioma (MPM) is the most common type in all malignant mesothelioma. The onset of MPM is associated with exposure to asbestos and it can have an incubation period of up to 40 years. The incidence of MPM has been increasing worldwide in recent years, so more attention has been focused on its diagnosis, treatment and prognosis. Activating mutations, amplifications and fusions/rearrangements of the anaplastic lymphoma kinase receptor tyrosine kinase (ALK) gene are commonly seen in patients with non-small cell lung cancer. However, it is rare in MPM. This current case report describes a female patient with advanced MPM with an ALK gene fusion mutation. In this particular case, treatment with crizotinib demonstrated some initial efficacy, which suggests that this might be a promising strategy for patients with advanced MPM with an ALK gene mutation. This required further research and evaluation in the future.}, } @article {pmid39516654, year = {2023}, author = {Gold, LT and Bray, SE and Kernohan, NM and Henderson, N and Nowicki, M and Masson, GR}, title = {The amino-acid stress sensing eIF2α kinase GCN2 is a survival biomarker for malignant mesothelioma.}, journal = {BJC reports}, volume = {1}, number = {1}, pages = {4}, pmid = {39516654}, issn = {2731-9377}, support = {119615//Tenovus/ ; }, abstract = {BACKGROUND: Malignant mesothelioma is a tumour that is strongly associated with a history of asbestos exposure, and which derives from mesothelial cells that line the serous cavities of the body. The tumour most commonly arises in the pleural cavity, but can also arise in the pericardium, peritoneum, and tunica vaginalis. At present the lesion has a very poor prognosis and is an incurable form of cancer with median survival times of up to 19 months being quoted for some histological subtypes. A large proportion of mesotheliomas have been shown to be arginine auxotrophic, leading to new research for therapeutics which might exploit this potential vulnerability.

METHODS: We measured the levels of General Control Non-derepressible 2 (GCN2) protein in malignant mesothelioma tumour samples and determined whether these levels correlate with clinical outcomes.

RESULTS: We observed that the expression levels of GCN2 correlated with patient survival and was an independent prognostic variable in pairwise comparisons with all available clinical data.

CONCLUSION: These findings suggest that GCN2 levels provides prognostic information and may allow for stratification of care pathways. It may suggest that targeting GCN2 is a viable strategy for mesothelioma therapy development.}, } @article {pmid39514167, year = {2024}, author = {Guglielmo, P and Crivellaro, C and Castello, A and Della Corte, CM and Pagano, M and Marchesi, S and Occhipinti, M and Zucali, PA and Evangelista, L}, title = {Emerging Radiopharmaceuticals in Pet Imaging for Mesothelioma: A Review of [[18]F]FDG Alternatives.}, journal = {Molecular diagnosis & therapy}, volume = {}, number = {}, pages = {}, pmid = {39514167}, issn = {1179-2000}, abstract = {Mesothelioma is a malignant tumor associated primarily with asbestos exposure, characterized by an aggressive nature and poor prognosis. Accurate diagnosis, staging, and monitoring of therapeutic response are crucial for effective patient management. Along with a computed tomography (CT) scan, fluorodeoxyglucose labeled with fluorine-18 ([[18]F]FDG) positron emission tomography (PET) is commonly used in mesothelioma evaluation. However, it has some limitations, including lower sensitivity after pleurodesis and poor accuracy for involved lymph node evaluation. Thus, there is the need to explore other agents. The aim of the present review is to analyze the current literature on the use of alternative radiopharmaceuticals for PET imaging in patients with mesothelioma. A comprehensive search of scientific databases (PubMed, Scopus, and Web of Science) for studies published in the last decade was performed by using the following keywords: "mesothelioma" AND "PET" AND "PET/CT" "radiopharmaceuticals", "[[18]F]FDG alternatives". Articles focused solely on [[18]F]FDG, non-English publications or preclinical studies, reviews, meeting abstracts, letters to the editors, and editorials were excluded. A qualitative assessment was made by using the Critical Appraisal Skills Programme (CASP) checklist for diagnostic test studies, when applicable. In total, 14 papers were selected; in seven articles more than five patients were enrolled, while the other seven were only clinical cases (enrolling up to two subjects). [[18]F]/gallium-68 ([[68]Ga])-labeled fibroblast activation protein inhibitor (FAPI) compounds, [[18]F]Fluorothymidine ([[18]F]FLT), methionine labeled with carbon-11 ([[11]C]MET), and fluoromisonidazole labeled with fluorine-18 ([[18]F]FMISO) PET/CT were the alternative agents used most often. In 12 articles, [[18]F]FDG PET/CT was used as a comparator imaging modality. Detection rate of [[18]F]FDG was similar to the other radiopharmaceuticals ([[68]Ga]/[18F]-labeled FAPI compounds, [[18]F]FLT, [[18]F]FMISO, [[11]C]MET, and [[68]Ga]-Pentaxifor), although radiolabeled FAPI seems to exhibit a higher diagnostic performance. [[18]F]FDG is still a valuable agent in patients with mesothelioma. However, radiolabeled FAPI appears to be promising and its theranostic properties should therefore be further assessed.}, } @article {pmid39507169, year = {2024}, author = {Lief, S and Patibandla, S and Ansari, AZ and Bhatt, N and Gulraiz, A and Beauti, SM and Ali, R}, title = {Ascites as a Rare Manifestation of Malignant Peritoneal Mesothelioma: A Case Report.}, journal = {Cureus}, volume = {16}, number = {10}, pages = {e70982}, doi = {10.7759/cureus.70982}, pmid = {39507169}, issn = {2168-8184}, abstract = {Malignant peritoneal mesothelioma (MPM) is an aggressive neoplasm that originates from the mesothelial cells lining the parietal peritoneum or visceral peritoneum and extensively spreads within the abdominal cavity. It is a rare malignancy characterized by an insidious onset and poor prognosis. We present the case of a 79-year-old Caucasian male who experienced escalating abdominal pain for six weeks and acute abdominal distension. His medical history was significant for hypertension, gastroesophageal reflux disease (GERD), hypercholesterolemia, and prior coronary artery bypass grafting (CABG). The patient had a 30-pack-year smoking history and worked as a plumber and roofer until retirement. We also confirmed with the patient that he has never been diagnosed with asbestosis. He reported no family history of mesothelioma or related conditions. A computed tomography (CT) scan revealed a prior sternotomy, mild pleural calcifications, mild hepatic steatosis, diffuse peritoneal ascites, diffuse omental edema, and pelvic phleboliths. MPM was confirmed through histopathological examination, which revealed atypical mesothelial cells with high nucleus-to-cytoplasm ratios, prominent nucleoli, and irregular nuclear membranes. It also revealed tumor cells positive for p53, calretinin, WT1, and podoplanin (D2-40). This case highlights the importance of considering MPM in the differential diagnosis for patients with ascites and possible asbestos exposure, particularly with respect to occupational hazards, as it is a rare manifestation of the disease.}, } @article {pmid39481034, year = {2024}, author = {Gilbert, A and Wieland, R and Zacher, N and Rieger, K and Berry, GJ and Novoa, R}, title = {Metastatic Mesothelioma of the Tunica Vaginalis Presenting as Scrotal and Abdominal Nodules: A Case Report and Review of the Literature.}, journal = {The American Journal of dermatopathology}, volume = {}, number = {}, pages = {}, doi = {10.1097/DAD.0000000000002848}, pmid = {39481034}, issn = {1533-0311}, abstract = {Mesothelioma of the tunica vaginalis testis (MMTVT) is a rare neoplasm comprising <3% of all cases of malignant mesothelioma (MM). MMTVT derives from the tunica vaginalis testis, an outpouching of the mesothelial-lined abdominal peritoneum that detaches from the abdominal cavity after the descent of the testis. Similar to pleural mesothelioma, asbestos exposure is a known risk factor. However, MMTVT has a better prognosis than pleural mesothelioma. Cutaneous metastases from MMTVT are exceedingly rare. Herein, we describe a case of a 67-year-old man with a history of asbestos exposure presenting with scrotal pain and indurated plaques on his lower abdomen and scrotum. Histologic sections showed a sheet-like dermal proliferation comprising epithelioid cells with necrosis and increased mitotic activity. The clinical and histologic differential diagnosis was broad, including metastatic carcinoma, melanoma, sarcoma, germ cell tumor, hematologic malignancy, neuroendocrine carcinoma, and malignant mesothelioma. By immunohistochemistry, the neoplastic cells were positive for WT1, D2-40, and AE1/AE3, with rare positivity for calretinin, consistent with a diagnosis of mesothelioma. Additional immunohistochemical studies provided no support for the other diagnostic considerations listed above. BAP1 showed retained nuclear expression (normal) by immunohistochemistry. A DNA sequencing panel identified copy number losses in CDKN2A, MTAP, CDKN2B, and NF2, which are frequently identified genetic alterations in malignant mesothelioma. Subsequent testicular imaging demonstrated a diffusely thickened scrotal wall with an enlarged left testicle. Overall, this represents a case of malignant mesothelioma presenting with cutaneous metastases to the scrotum and lower abdomen, with clinical and imaging features suggestive of primary MMTVT. The International Mesothelioma Interest Group recommends using at least 2 mesothelial markers, such as calretinin, WT1, CK5/6 or D2-40, and 2 epithelial markers, such as claudin-4, CEA, MOC-31, as well as a broad-spectrum cytokeratin stain (AE1/AE3) as part of an initial immunohistochemical panel. Metastatic mesothelioma should be included in the differential diagnosis of malignant epithelioid dermal tumors with unusual staining patterns.}, } @article {pmid39474071, year = {2024}, author = {Behrouzfar, K and Mutsaers, SE and Chin, WL and Patrick, K and Ng, IT and Pixley, FJ and Morahan, G and Lake, RA and Fisher, SA}, title = {Mesothelioma survival prediction based on a six-gene transcriptomic signature.}, journal = {iScience}, volume = {27}, number = {10}, pages = {111011}, pmid = {39474071}, issn = {2589-0042}, abstract = {Mesothelioma is a lethal cancer. Despite promising outcomes associated with immunotherapy, durable responses remain restricted to a minority of patients, highlighting the need for improved strategies that better predict outcome. Here, we described the development of a mesothelioma-specific gene signature that accurately predicts survival. Comprehensive gene expression analysis of asbestos exposed MexTAg Collaborative Cross mouse tumors revealed distinct tumor clusters characterized by epithelial mesenchymal transition/extracellular matrix, or immune infiltrate related gene expression profiles. Weighted gene co-expression network analysis (WGCNA) identified 20 hub genes that drove differential gene expression. Human homologues of these 20 hub genes were refined through univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses to identify a six-gene mesothelioma-specific prognostic signature that accurately predicted patient survival across four independent human mesothelioma datasets. Furthermore, this six-gene signature demonstrated the potential to predict treatment response, thus advancing the management of this challenging malignancy.}, } @article {pmid39472148, year = {2024}, author = {Mei, W and Yang, SJ and Zhang, YP}, title = {[Establishment and research progress of early diagnosis system for pleural mesothelioma].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {42}, number = {10}, pages = {793-800}, doi = {10.3760/cma.j.cn121094-20230915-00060}, pmid = {39472148}, issn = {1001-9391}, support = {202301BA070001-26, 202301BA070001-027//Special Basic Cooperative Research Programs of Yunnan Provincial Undergraduate Universities/ ; 81560458, 31601155//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Mesothelioma/diagnosis ; *Pleural Neoplasms/diagnosis ; *Early Detection of Cancer/methods ; MicroRNAs/blood ; Lung Neoplasms/diagnosis ; Biomarkers, Tumor/blood ; Breath Tests ; Early Diagnosis ; Mesothelioma, Malignant/diagnosis ; }, abstract = {Pleural mesothelioma (PMe) was associated with asbestos exposure.The Diagnosis of PMe is difficult due to the lack of specificity of clinical signs and symptoms, although there are many tools available for early diagnosis of mesothelioma. Most PMe patients are diagnosed at an advanced stage. This article reviews advances in strategies for early diagnosis of mesothelioma, focusing on breath analysis, early diagnosis of pleural effusion cytology in patients with mesothelioma, serum biomarkers and miRNA.}, } @article {pmid39469233, year = {2024}, author = {Santos, C and Sacadura-Leite, E and Feijó, S and Dixe, MDA and Astoul, P and Sousa-Uva, A}, title = {Translation, Cultural Adaptation, and Content Validation of a Pleural Mesothelioma Questionnaire to Portuguese Context - A Key Tool for Epidemiological Surveillance.}, journal = {Portuguese journal of public health}, volume = {42}, number = {2}, pages = {101-110}, pmid = {39469233}, issn = {2504-3145}, abstract = {OBJECTIVE: The main objective of this study was to describe the translation, cultural adaptation, and content validation process of the French National Surveillance Programme for Pleural Mesothelioma (FNSPPM) questionnaire for the Portuguese context.

METHODS: A search was conducted in the PubMed database and Web of Science, in the period from January 1, 1960, to December 31, 2022, to select the questionnaire. Forward and reverse translations, calculation of the content validity index (CVI) by a panel of experts (n = 9), and cognitive interviewing with individuals with at least one exposure to asbestos (n = 10) were performed. Experts rated items on a Likert scale (1-4) based on their relevance. The item-level content validity index (I-CVI), scale-level content validity index based on the average method (S-CVI/Ave), and scale-level content validity index based on the universal agreement method (S-CVI/UA) were calculated.

RESULTS: The final version of the FNSPPM questionnaire for the Portuguese context resulted from a translation and content validation process. The panel of experts considered the questionnaire relevant, with an I-CVI of up to 0.78 in 68 of 69 of the questions, an S-CVI/Ave of 0.98, and an S-CVI/UA of 0.90. The participants in the cognitive interviews reported an understanding of the questionnaire.

CONCLUSION: A validated FNSPPM questionnaire for the Portuguese context is now available to study individuals with pleural mesothelioma (PM) and asbestos exposure.}, } @article {pmid39469260, year = {2023}, author = {Santos, C and Dixe, MDA and Sacadura-Leite, E and Astoul, P and Sousa-Uva, A}, title = {Asbestos Exposure and Malignant Pleural Mesothelioma: A Systematic Review of Literature.}, journal = {Portuguese journal of public health}, volume = {40}, number = {3}, pages = {188-202}, pmid = {39469260}, issn = {2504-3145}, abstract = {BACKGROUND: The relationship between exposure to asbestos and malignant pleural mesothelioma (MPM) is already well established. Nevertheless, much remains to be known about exposure thereto and the incidence and mortality from MPM.

OBJECTIVE: This systematic review aims to map the relationship between asbestos and MPM by studying the exposure to asbestos and the incidence and mortality of MPM.

METHODS: A systematic review was conducted relating asbestos and MPM. Exposure to asbestos, incidence, and mortality by MPM was reviewed. PubMed, Web of Science, Cochrane Library, RCAAP, DART-Europe, and the reference lists of included studies were searched, from January 1, 1960, to December 31, 2020. Methodological quality was checked, the risk of bias analysis was performed, a level of evidence grade was assigned, and descriptive data analysis was performed.

RESULTS: 3,484 unique citations were identified, which included seventeen observational studies that met inclusion criteria with a total of 1,104 patients. Heterogeneity is present between the included studies which range from a case series of 16 retrospective studies and 1 prospective study. Studies were mostly conducted in Europe, particularly in Italy (6), and were published between 1969 and 2020. The mean age of patients is approximately 66 years with a latency period between the first exposure and diagnosis of approximately 42 years. 14 studies present data regarding the occupational context and chrysotile and crocidolite are the most studied types of fibre. The incidence of cases occurred between the interval 1966 and 2014 and in 9 studies the mortality rate was 100% of patients.

CONCLUSION: There is high evidence to support the relationships between asbestos and MPM. However, the relatively scant information provided by the studies reinforces the need for well-conducted research and implementation of National Mesothelioma Surveillance Centres at a global level.}, } @article {pmid39447016, year = {2024}, author = {Stevens, ME and Tuttle, BP and Brew, DW and Paustenbach, DJ}, title = {An evaluation of trends for mesothelioma mortality in American women: Addressing the content of a recent Morbidity and Mortality Weekly Report (MMWR).}, journal = {Toxicology and industrial health}, volume = {}, number = {}, pages = {7482337241293201}, doi = {10.1177/07482337241293201}, pmid = {39447016}, issn = {1477-0393}, abstract = {Mesothelioma is a fatal disease that has historically been associated with exposure to airborne asbestos. Because occupational asbestos exposures dropped dramatically in the late 1960s and early 1970s, far fewer cases of mesothelioma today are due to these fibers but, instead, are usually a result of the aging process or genetic predisposition. In May of 2022, a Morbidity and Mortality Weekly Report (MMWR) was issued by the Centers for Disease Control and Prevention (CDC) regarding malignant mesothelioma incidence in women from 1999 to 2020. While this MMWR alerted citizens to the continued presence of the disease, after reading this article one might have thought that the CDC was suggesting that the disease was increasing in women due to asbestos exposures (which it is not). In the present analysis, we investigate several factors related to the interpretation of epidemiological data for mesothelioma, including the role of asbestos as a risk factor over time. The authors conducted a review of the scientific community's understanding of mesothelioma incidence and asbestos exposures amongst women, as well as an investigation of the methods and references in the MMWR article. Although various articles have recently discussed the incidence of both peritoneal and pleural mesothelioma in women, it is fortunate that the age-adjusted rates for mesothelioma have remained flat (neither increased nor decreased significantly) in women for the past 50 years. Incredibly few women in the U. S. have had appreciable cumulative exposures to any type of asbestos (chrysotile, amosite, or crocidolite) in the workplace or from the ambient environment, especially since about 1965-1970. In this paper, we highlight six factors that should be considered when evaluating the incidence of mesothelioma amongst American women in the current era. Without sufficient consideration of these factors, improper conclusions have been drawn over the past several years.}, } @article {pmid39445262, year = {2024}, author = {Paremuzyan, A and Onwubuya, E and Mathews, J}, title = {A Case of Malignant Pleural Mesothelioma With Unknown Asbestos Exposure.}, journal = {Cureus}, volume = {16}, number = {9}, pages = {e69966}, pmid = {39445262}, issn = {2168-8184}, abstract = {Malignant pleural mesothelioma (MPM) is a rare, locally invasive tumor that develops from mesothelial cells lining the lung's pleura. It is mostly associated with prolonged asbestos exposure. The long latency period between asbestos exposure and clinical symptoms makes diagnosing MPM challenging. This report describes a 57-year-old Hispanic female who presented with a persistent nonproductive cough and was ultimately diagnosed with advanced-stage pleural mesothelioma after extensive work-up. It highlights the difficulties in diagnosing MPM in patients without apparent asbestos exposure independent of age or gender.}, } @article {pmid39441675, year = {2024}, author = {Suehiro, T and Ahmad, KM and Hoang, NTD and Xu, B and Komatsu, H and Kurachi, K and Nikawa, H and Mine, Y and Matsuki, T and Asano, K and Fujii, M}, title = {Activation of platelet-derived growth factor receptors regulate connective tissue growth factor protein levels via the AKT pathway in malignant mesothelioma cells.}, journal = {Journal of biochemistry}, volume = {}, number = {}, pages = {}, doi = {10.1093/jb/mvae068}, pmid = {39441675}, issn = {1756-2651}, abstract = {The incidence of malignant mesothelioma (MM), a disease linked to refractory asbestos exposure, continues to increase globally, and remains largely resistant to various treatments. Our previous studies have identified a strong correlation between connective tissue growth factor (CTGF) protein expression and MM malignancy, underscoring the importance of understanding CTGF regulation in MM cells. In this study, we demonstrate for the first time that stimulation with platelet-derived growth factor receptor (PDGFR) ligand, PDGF-BB, increases CTGF protein expression levels without affecting CTGF mRNA levels. Inhibition of PDGFR resulted in a reduction of CTGF protein expression, indicating that PDGFR activation is essential in regulating CTGF protein expression in MM cells. PDGF-BB also activated the protein kinase B (AKT) pathway, and inhibition of AKT phosphorylation abolished the PDGFR-induced CTGF protein expression, suggesting that PDGFR acts upstream of CTGF via the AKT pathway. This reinforces the role of CTGF protein as a key regulator of MM malignancy. Additionally, PDGFR activation led to the phosphorylation of mTOR and 4E-BP1, critical regulators of protein synthesis downstream of AKT, suggesting that PDGFR controls CTGF protein expression through the regulation of CTGF mRNA translation.}, } @article {pmid39439640, year = {2024}, author = {Guerra, J and Pina, JM and Andrade, V and Cassis, J and Campos Pinheiro, L}, title = {Malignant Mesothelioma of the Tunica Vaginalis: About a Rare Clinical Case.}, journal = {Cureus}, volume = {16}, number = {9}, pages = {e69897}, pmid = {39439640}, issn = {2168-8184}, abstract = {Malignant mesothelioma (MM) of the tunica vaginalis is an exceedingly rare neoplasm, with fewer than 300 cases reported in the medical literature. Due to its rarity, epidemiology, and risk factors are still unclear, and it is unknown whether asbestos or chronic inflammatory conditions play a role in etiology. This case study presents a 70-year-old male patient with MM of the tunica vaginalis, detailing the diagnostic challenges, treatment procedures, and eventual progression to palliative care. The study underscores the importance of accurate diagnosis and the aggressive nature of the disease despite treatment efforts.}, } @article {pmid39434641, year = {2024}, author = {Visonà, SD and Pace, MC and Consonni, D and Mensi, C}, title = {Accuracy of the Lombardy Mesothelioma Registry: comparison with the autopsy database of Pavia University (Lombardy Region, Northern Italy).}, journal = {Epidemiologia e prevenzione}, volume = {48}, number = {4-5}, pages = {320-325}, doi = {10.19191/EP24.4-5.A736.096}, pmid = {39434641}, issn = {1120-9763}, mesh = {Humans ; Italy/epidemiology ; *Registries ; *Autopsy ; *Mesothelioma/mortality/pathology/epidemiology ; Male ; *Sensitivity and Specificity ; *Databases, Factual ; Female ; Aged ; Middle Aged ; Incidence ; Asbestos/adverse effects ; Universities ; }, abstract = {OBJECTIVES: to evaluate the accuracy (completeness of case recording and diagnostic quality) of the Lombardy Mesothelioma Registry (Registro Mesoteliomi Lombardia, RML) through a comparison with the autopsy database of Pavia University (years 2000-2016).

DESIGN: validation study.

SETTING AND PARTICIPANTS: all mesothelioma records with incidence date between 01.01.2000 and 16.09.2016 were extracted from the RML. They were cross-referenced with deaths from any asbestos-related disease subjected to a forensic autopsy extracted from the archive of the Department of Public Health, Experimental and Forensic Medicine of Pavia University.

MAIN OUTCOMES MEASURES: using the postmortem diagnosis by Pavia University as the gold standard, RML sensitivity and specificity and their 95% confidence intervals (95%CI) were calculated using the Agresti-Coull formula.

RESULTS: based on 141 deaths, the RML showed very good accuracy: specificity was 100% (95%CI 87%-100%; 32/32 deaths) and sensitivity 94% (95%CI 87%-97%; 102/109 deaths). The 7 false negative cases either were missed by the RML (N. 4) or had been wrongly classified as non-mesotheliomas (N. 3) because the diagnosis was made or confirmed only postmortem after a forensic autopsy.

CONCLUSIONS: RML accuracy (completeness and diagnostic quality) was very high. No false positive was found and the few false negatives were due to lack of notification of mesotheliomas diagnosed postmortem to the registry. Forensic pathologists should be made aware that mesothelioma notification to the regional mesothelioma registry is important and compulsory.}, } @article {pmid39430319, year = {2024}, author = {Ye, L and Ryu, H and Granadier, D and Nguyen, LT and Simoni, Y and Dick, I and Firth, T and Rouse, E and Chiang, P and Lee, YCG and Robinson, BW and Creaney, J and Newell, EW and Redwood, AJ}, title = {Stem-like exhausted CD8 T cells in pleural effusions predict improved survival in non-small cell lung cancer (NSCLC) and mesothelioma.}, journal = {Translational lung cancer research}, volume = {13}, number = {9}, pages = {2352-2372}, pmid = {39430319}, issn = {2218-6751}, abstract = {BACKGROUND: Anti-tumor CD8 T cells are important for immunity but can become 'exhausted' and hence ineffective. Tumor-infiltrating exhausted CD8[+] T cells include less differentiated stem-like exhausted T (Tex[stem]) cells and terminally exhausted T (Tex[term]) cells. Both subsets have been proposed as prognostic biomarkers in cancer patients. In this study, we retrospectively investigated their prognostic significance in patients with metastatic non-small cell lung cancer (NSCLC) and validated our findings in a mesothelioma cohort.

METHODS: Pre-treatment malignant pleural effusions (PEs) from 43 NSCLC (41 non-squamous, 2 squamous) patients were analyzed by flow cytometry. The percentages of Tex[stem] and Tex[term] CD8 T cells were correlated with overall survival (OS) after adjusting for clinicopathological variables. Findings were validated using a mesothelioma cohort (n=49). Mass cytometry was performed on 16 pre-treatment PE samples from 5 mesothelioma and 3 NSCLC patients for T-cell phenotyping. Single-cell multi-omics analysis was performed on 4 pre-treatment PE samples from 2 NSCLC patients and 2 mesothelioma patients for analysis of the transcriptomic profiles, surface markers and T cell receptor (TCR) repertoire.

RESULTS: Higher frequency of Tex[stem] was associated with significantly increased OS [median 9.9 vs. 3.4 months, hazard ratio (HR) 0.36, 95% CI: 0.16-0.79, P=0.01]. The frequency of Tex[term] was not associated with OS. These findings were validated in the mesothelioma cohort (high vs. low Tex[stem], median OS 32.1 vs. 19.8 months, HR 0.31, 95% CI: 0.10-0.96, P=0.04). Detailed single-cell sequencing and mass cytometry profiling revealed that exhausted T cells from NSCLC expressed greater stem-likeness and less inhibitory markers than those from mesothelioma and that Tex[stem] cells also contained 'bystander' virus-specific T cells.

CONCLUSIONS: This study demonstrates that PE CD8 Tex[stem] cell abundance is associated with better survival outcomes, and thus may be a useful prognostic biomarker.}, } @article {pmid39410011, year = {2024}, author = {Stella, GM and Lisini, D and Pedrazzoli, P and Galli, G and Bortolotto, C and Melloni, G and D'Ambrosio, G and Klersy, C and Grosso, A and Paino, F and Tomaselli, S and Saracino, L and Alessandri, G and Pessina, A and Grignani, E and Rosti, V and Corsico, AG and Comoli, P and Agustoni, F}, title = {Phase I Clinical Trial on Pleural Mesothelioma Using Neoadjuvant Local Administration of Paclitaxel-Loaded Mesenchymal Stromal Cells (PACLIMES Trial): Study Rationale and Design.}, journal = {Cancers}, volume = {16}, number = {19}, pages = {}, doi = {10.3390/cancers16193391}, pmid = {39410011}, issn = {2072-6694}, support = {PLAGENCELL//Fondazione Regionale per la Ricerca Biomedica , PLAGENCELL project - A network for cell and gene therapies for devastating diseases (grant to A.G.C. and P.C.)/ ; }, abstract = {Background and rationale. Pleural mesothelioma (PM) is a rare and aggressive neoplasm that originates from the pleural mesothelium and whose onset is mainly linked to exposure to asbestos, which cannot be attacked with truly effective therapies with consequent poor prognosis. The rationale of this study is based on the use of mesenchymal stromal cells (MSCs) as a vehicle for chemotherapy drugs to be injected directly into the pathological site, such as the pleural cavity. Study design. The study involves the use of a conventional chemotherapeutic drug, Paclitaxel (PTX), which is widely used in the treatment of different types of solid tumors, including PM, although some limitations are related to pharmacokinetic aspects. The use of PTX-loaded MSCs to treat PM should provide several potential advantages over the systemically administered drug as reduced toxicity and increased concentration of active drug in the tumor-surrounding context. The PACLIMES trial explores the safety and toxicity of the local administration of Paclimes in chemonaive patients, candidates for pleurectomy. The secondary objective is to find the effective Paclimes dose for subsequent phase II studies and to observe and record the antitumor activity. Future direction. The experimental pre-clinical background and rationale are discussed as well.}, } @article {pmid39409190, year = {2024}, author = {Chiec, L and Bruno, DS}, title = {Immunotherapy for Treatment of Pleural Mesothelioma: Current and Emerging Therapeutic Strategies.}, journal = {International journal of molecular sciences}, volume = {25}, number = {19}, pages = {}, doi = {10.3390/ijms251910861}, pmid = {39409190}, issn = {1422-0067}, mesh = {Humans ; *Immunotherapy/methods ; *Pleural Neoplasms/therapy/immunology/pathology ; *Mesothelioma/therapy/immunology/pathology ; Immune Checkpoint Inhibitors/therapeutic use ; Mesothelioma, Malignant/therapy/pathology ; Clinical Trials as Topic ; }, abstract = {Pleural mesothelioma is a rare malignancy associated with asbestos exposure and very poor prognosis, with a 5-year overall survival of 12%. Outcomes may vary according to stage at time of diagnosis and histologic subtype. Most recently, clinical trials utilizing dual checkpoint inhibitor regimens and chemotherapy in combination with immune oncologic agents have demonstrated impactful changes in outcomes. In this article, we review studies that have led to the successful implementation of immunotherapy in clinical practice for the treatment of this disease and highlight ongoing clinical trials exploring the use of different immunotherapy strategies for the treatment of pleural mesothelioma. We also discuss the challenges of immunotherapy-based approaches in the context of mesothelioma and future strategies currently being investigated to overcome them.}, } @article {pmid39407894, year = {2024}, author = {Jain, M and Crites, MK and Rich, P and Bajantri, B}, title = {Malignant Pleural Mesothelioma: A Comprehensive Review.}, journal = {Journal of clinical medicine}, volume = {13}, number = {19}, pages = {}, doi = {10.3390/jcm13195837}, pmid = {39407894}, issn = {2077-0383}, abstract = {Mesotheliomas are hyperplastic tumors that envelop the serosal membranes that safeguard the body's external surfaces. Although certain instances may exhibit indolent characteristics, a significant number of tumors demonstrate rapid progression and a poor prognosis. Mesotheliomas are typically categorized as benign or malignant, with malignant mesothelioma being more frequently linked to asbestos exposure. Malignant pleural mesothelioma (MPM) predominantly impacts males and often emerges in the late 50 s or beyond, characterized by a median age of early 70 s among patients exposed to asbestos lasting from 2 to 4 decades. Respiratory exposure to asbestos particles leads to the development of malignant mesothelioma, characterized by recurrent inflammation, disruption of cell division, activation of proto-oncogenes, and generation of free radicals. In pleural mesothelioma, BAP1, CDKN2A, and NF are the most often mutated genes. Accurate diagnosis and assessment usually require the use of chest computed tomography (CT) scans, magnetic resonance imaging (MRI), and positron emission tomography (PET). Radiation therapy, immunotherapy, chemotherapy, and surgery are some of the treatment options that are currently available. This systematic review provides a comprehensive analysis of the latest research, biomarkers, evaluation, and management strategies for malignant pleural mesothelioma.}, } @article {pmid39400365, year = {2024}, author = {Arrandale, VH and Berriault, C and Song, C and DeBono, N and Demers, PA}, title = {Surveillance of asbestos related disease among workers enrolled in an exposure registry.}, journal = {American journal of industrial medicine}, volume = {}, number = {}, pages = {}, doi = {10.1002/ajim.23668}, pmid = {39400365}, issn = {1097-0274}, support = {//Ontario Ministry of Labour, Immigration, Training and Skills Development/ ; }, abstract = {INTRODUCTION: Contemporary asbestos exposure occurs during construction, remediation, and maintenance involving asbestos-containing materials (ACM), as compared to the historical exposure scenarios of asbestos mining and milling. The Ontario Asbestos Workers Register (AWR) was established in 1986 to track asbestos exposure among construction workers. This study reports on the risk of asbestos-related diseases (ARD) among workers in the AWR.

METHODS: AWR registrants were linked probabilistically with administrative health databases (1986-2019) to identify cases of ARD including both cancer and chronic respiratory disease. Follow-up began at AWR enrollment and continued prospectively. Incidence rates were compared to the general population using standardized incidence ratios (SIRs). Associations between ACM exposure and ARD were estimated among AWR registrants using Poisson regression.

RESULTS: In total, 26,204 (81%) registrants were linked successfully. Common industries of employment were construction (62%), manufacturing (19%) and education (8%). Among men and women mesothelioma (M:SIR 6.83 [95% CI = 5.56-8.31]; W:SIR 19.2 [3.86-56.1]) and pulmonary fibrosis (M:SIR 14.1 [12.2-16.2]; W:SIR 9.25 [2.49-23.7]) rates were higher than the general population. Asbestosis risk was elevated among men (M:SIR 11.2 [9.59-13.1]). Workers with longer reported exposures (≥140 h) had increased rates of lung cancer (RR 1.34 [1.10-1.63]), mesothelioma (RR 2.83 [1.75-4.58]), asbestosis (RR 3.07 [2.12-4.43]), chronic obstructive pulmonary disease (RR 1.42 [1.29-1.57]), and pulmonary fibrosis (RR 1.88 [1.35-2.62]).

CONCLUSION: Exposure to asbestos in construction and building maintenance continues to contribute to ARD incidence. Despite a Canadian ban on asbestos in new products, exposures to existing ACM will persist from construction activities. The AWR offers an opportunity for ongoing surveillance of resulting ARD in Ontario.}, } @article {pmid39394704, year = {2024}, author = {Li, R and Yu, WK and Wang, Q and Zhu, LJ and Zhang, FF}, title = {[Expression changes of miRNAs and EMT-related genes in human mesothelial cells induced by long-term exposure to asbestos].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {42}, number = {9}, pages = {668-672}, doi = {10.3760/cma.j.cn121094-20240112-00014}, pmid = {39394704}, issn = {1001-9391}, support = {LQY18H260001, LGD21C040008//Natural Science Foundation of Zhejiang Province/ ; YS2022012//Special Plan Project of Hangzhou Medical College Institute/ ; }, mesh = {Humans ; *MicroRNAs/genetics/metabolism ; *Epithelial-Mesenchymal Transition/drug effects ; *Asbestos, Serpentine/toxicity ; Epithelial Cells/metabolism/drug effects ; Asbestos/toxicity ; Mesothelioma/genetics/chemically induced ; Cell Line, Tumor ; Cadherins/genetics/metabolism ; Vimentin/metabolism/genetics ; Cell Line ; Pleural Neoplasms/genetics/chemically induced/metabolism ; }, abstract = {Objective: To investigate the effects of long-term exposure to chrysotile and crocidolite on miRNAs and epithelial mesenchymal transformation (EMT) -related gene expression in human pleural mesothelial cells. Methods: In November 2020, fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect the expressions of EMT-related genes in human pleural mesothelioma cells (NCl-H2052 cells, NCl-H2452 cells) and human normal mesothelial cells (Met-5A cells). MiRNAs with abnormal expression in human pleural mesothelioma cells were screened out from the previous miRNA chip data of research group, and target genes of differentially expressed miRNAs were predicted using miRWalk database (http: //mirwalk.umm.uni-heidelberg.de). RT-qPCR was used to verify the abnormal expression of EMT-related miRNAs in cell lines. Met-5A cells were treated with 5μg/cm(2) chrysotile and crocidolite respectively for 48 h a time, once a week and a total of 10 times. Chrysotile group, crocidolite group and control group were set up. And the control group was added with the same volume of PBS. The expression changes of EMT-related genes and abnormal expression miRNAs in each group were detected by RT-qPCR. The differences among the groups were compared by one-way ANOVA, and the differences between the control group and the experimental group were compared by dunnet-t test. Results: Compared with Met-5A cells, the expression levels of Vimentin and Twist genes were increased, and the expression level of E-cadherin genes was decreased in NCl-H2052 cells and NCl-H2452 cells (P<0.001). Target genes of miRNAs with abnormal expression in miRNA chip were predicted, and the results showed four abnormally expressed miRNAs associated with EMT and verified the expression of these four miRNAs in the cell lines. Compared with Met-5A cells, the expression level of hsa-miR-155-5p was increased in NCl-H2052 cells and NCl-H2452 cells, the expression levels of hsa-miR-34b-5p, hsa-miR-34c-5p and hsa-miR-28-5p were decreased in NCl-H2052 cells and NCl-H2452 cells (P<0.001), which was consistent with the results of chip analysis. After exposure of Met-5A cells, it was found that compared with the control group, the expression levels of Vimentin and Twist genes, hsa-miR-155-5p, hsa-miR-34b-5p and hsa-miR-34c-5p in the crocidolite group were increased, while the expression level of E-cadherin gene was decreased (P<0.05). Compared with the control group, the expression levels of Vimentin, Twist and E-cadherin genes in chrysotile group were increased, while the expression levels of hsa-miR-34b-5p, hsa-miR-34c-5p and hsa-miR-28-5p were decreased (P<0.05) . Conclusion: Long-term exposure to chrysotile and crocidolite could cause Met-5A cells to produce miRNAs and EMT-related gene expression changes similar to mesothelioma cells.}, } @article {pmid39377019, year = {2024}, author = {Rezvani, A and Shahriarirad, R and Jahanshahi, S and Fouladi, D and Tavallali, M and Ziaian, B and Fallahi, MJ}, title = {The aftermath of asbestos prohibition in industry and its association with malignant mesothelioma in the south of Iran: An enduring predicament yet to be resolved.}, journal = {Health science reports}, volume = {7}, number = {10}, pages = {e70117}, pmid = {39377019}, issn = {2398-8835}, abstract = {PURPOSE: Malignant Mesothelioma (MM) is a rare malignancy of the serosa membranes with a high mortality rate and long latent period. The relationship between a group of mineral fibers known as asbestos and mesothelioma is now well accepted in which people can be exposed to these fibers by various means during their lifetime and has been its usage has banned in many countries, such as Iran, which announced its gradual elimination from 1999 over a period of 7 years by using safe substitutes. However, the mineral particles are able to sustain itself in the environment, air, water, and soil and on the other hand, symptoms may take up to half a century to develop in exposed individuals. Also, there remains a shortage of comprehensive investigation on the effects of asbestos exposure within the familial context (household or domestic exposure) or on individuals residing in proximity to asbestos mines or factories (environmental exposure). Based on the high number of MM cases in Iran, and also our hypothesis that residuals of asbestos in the environment and petroleum products may be the etiological factor for MM, we conducted this study to evaluate the clinic epidemiological features of MM in the south of Iran its relation to possible asbestos exposure.

METHODS: In this study, we analyzed the demographic features and occupations of confirmed cases of MM in Shiraz, southern Iran along with the follow-up of the patients' disease from 2008 to 2018, while also comparing the features of our patients with a control group compromising of 105 non-MM patients.

RESULTS: Among the 35 confirmed cases of MM, with an average age of 61 years, 9 (25.7%) were female, and 26 (74.3%) were male. During our assessment, 12 patients had already died, with a mean time of 11.26 months post-diagnosis. Our findings revealed a higher prevalence of MM among housekeepers and employees of oil companies. In comparison to the control group, individuals with occupational exposure and those residing near refinery locations were at a heightened risk of developing MM. However, based on regression analysis, only occupations associated with refineries exhibited a significant correlation with MM (p = 0.028; OR: 14.602; 95% CI: 1.328-160.499).

CONCLUSION: Both occupational and para-occupational exposure demonstrated a significant correlation with MM, whereas our regression analysis did not affirm geographical and environmental factors as contributors to MM. Despite the industry's prohibition of direct asbestos usage, the persistent existence of asbestos particles in the environment for decades, coupled with the long latency period of MM, warrants further investigation. Health authorities and policymakers should recognize this potential hazard, prompting an enhancement of early detection within at-risk groups.}, } @article {pmid39371847, year = {2024}, author = {R, PD and Grace Priyadarshini, S and P, J}, title = {Malignant Mesothelioma: Overcoming Diagnostic Hurdles.}, journal = {Cureus}, volume = {16}, number = {9}, pages = {e68718}, pmid = {39371847}, issn = {2168-8184}, abstract = {Malignant pleural mesothelioma, an aggressive neoplasm frequently linked to asbestos exposure, is often detected at an advanced stage. This report details the case of a 58-year-old mason who presented with left-sided chest pain, and shortness of breath, accompanied by weight loss for a month. A positron emission tomography (PET) scan revealed increased uptake along the pleural surface, as well as in several mediastinal lymph nodes and the left supraclavicular lymph node. Thoracoscopy revealed the presence of multiple nodules on the costal pleura. Despite repeated negative results from pleural effusion cytology, cell block analysis, and pleural biopsies, the diagnosis of malignant mesothelioma (MM) was ultimately established through an ultrasound-guided (USG) biopsy of the left supraclavicular lymph node, with immunohistochemical confirmation using calretinin.}, } @article {pmid39337157, year = {2024}, author = {Porzio, A and Feola, A and Salzillo, C and Corbi, G and Campobasso, CP}, title = {Colorectal Cancer and Asbestos Exposure: A Women's Health Perspective.}, journal = {Healthcare (Basel, Switzerland)}, volume = {12}, number = {18}, pages = {}, pmid = {39337157}, issn = {2227-9032}, abstract = {BACKGROUND: Colorectal cancer (CRC) is considered a "man's disease". However, emerging data show that females may have a higher prevalence of certain risk factors. A potential causal role of asbestos in CRC carcinogenesis has been suggested. This relationship is controversial, and only a few studies have focused on exposed female populations. The aim of this study was to review the scientific literature related to asbestos-related CRC incidence and mortality rates in female populations to address gender bias in the existing research.

METHODS: A systematic review was performed following PRISMA statement.

RESULTS: Fourteen studies reporting 92 cases in total were included. Most women were aged 50 years or older and were employed in occupational activities with high asbestos exposure (steel, textile, and asbestos-cement industry) for at least 10 years. In one single case, household asbestos exposure was reported. The colon was the primary location of the tumor in 47 out of 92 cases. Three women were also affected by synchronous or metachronous peritoneal mesotheliomas.

CONCLUSIONS: This study revealed a general methodological "gender bias" in scientific research. A significantly higher representation of women in clinical studies is needed to clarify the link between asbestos exposure and the development of colorectal cancer.}, } @article {pmid39329996, year = {2024}, author = {Roca, E and Aujayeb, A and Astoul, P}, title = {Diagnosis of Pleural Mesothelioma: Is Everything Solved at the Present Time?.}, journal = {Current oncology (Toronto, Ont.)}, volume = {31}, number = {9}, pages = {4968-4983}, pmid = {39329996}, issn = {1718-7729}, mesh = {Humans ; *Pleural Neoplasms/diagnosis/therapy ; *Mesothelioma, Malignant/diagnosis/therapy/pathology ; Mesothelioma/diagnosis/therapy ; Lung Neoplasms/diagnosis/therapy ; Biopsy/methods ; Thoracic Surgery, Video-Assisted/methods ; }, abstract = {Ranked high in worldwide growing health issues, pleural diseases affect approximately one million people globally per year and are often correlated with a poor prognosis. Among these pleural diseases, malignant pleural mesothelioma (PM), a neoplastic disease mainly due to asbestos exposure, still remains a diagnostic challenge. Timely diagnosis is imperative to define the most suitable therapeutic approach for the patient, but the choice of diagnostic modalities depends on operator experience and local facilities while bearing in mind the yield of each diagnostic procedure. Since the analysis of pleural fluid cytology is not sufficient in differentiating historical features in PM, histopathological and morphological features obtained via tissue biopsies are fundamental. The quality of biopsy samples is crucial and often requires highly qualified expertise. Since adequate tissue biopsy is essential, medical or video-assisted thoracoscopy (MT or VATS) is proposed as the most suitable approach, with the former being a physician-led procedure. Indeed, MT is the diagnostic gold standard for malignant pleural pathologies. Moreover, this medical or surgical approach can allow diagnostic and therapeutic procedures: it provides the possibility of video-assisted biopsies, the drainage of high volumes of pleural fluid and the administration of sterile calibrated talcum powder under visual control in order to achieve pleurodesis, placement of indwelling pleural catheters if required and in a near future potential intrapleural therapy. In this context, dedicated diagnostic pathways remain a crucial need, especially to quickly and properly diagnose PM. Lastly, the interdisciplinary approach and multidisciplinary collaboration should always be implemented in order to direct the patient to the best customised diagnostic and therapeutic pathway. At the present time, the diagnosis of PM remains an unsolved problem despite MDT (multidisciplinary team) meetings, mainly because of the lack of standardised diagnostic work-up. This review aims to provide an overview of diagnostic procedures in order to propose a clear strategy.}, } @article {pmid39316223, year = {2024}, author = {Pacella, A and Ballirano, P and Di Carlo, MC and Altieri, A and Paccapelo, M and Skogby, H and Campopiano, A and Bruno, MR and Croce, A and Piersante, C and Apollaro, C and Malvasi, G and Bruni, BM and Bloise, A}, title = {Geological and mineralogical characterization of fibrous tremolite from Iacolinei quarry (Basilicata, Italy).}, journal = {Environmental geochemistry and health}, volume = {46}, number = {11}, pages = {429}, pmid = {39316223}, issn = {1573-2983}, support = {B87G23000090005//National Institute for Insurance against Accidents at Work (INAIL) - BRIC 2022 project/ ; }, mesh = {Italy ; *Asbestos, Amphibole/analysis ; X-Ray Diffraction ; Geologic Sediments/chemistry ; Environmental Monitoring ; }, abstract = {Naturally Occurring Asbestos (NOA) has drawn the attention worldwide when investigation revealed an increased incidence of malignant mesothelioma in population living near NOA sites. In Basilicata region (South Italy), population living in the villages of Castelluccio Superiore and Inferiore, Lauria, Latronico, Episcopia, San Severino Lucano, and Francavilla in Sinni may be considered at high risk of asbestos exposure because these villages are either surrounded by or built on NOA-rich ophiolitic outcrops. In this work we investigated an asbestos tremolite sample coming from the ophiolitic rocks outcropping in the quarry of Iacolinei, widely used in the past to extract aggregates for various applications. A detailed mineralogical characterization has been attained by using a multi-analytical approach (EMPA, SEM-EDS, TEM-EDS, Mössbauer, µ-Raman, X-ray powder diffraction, and thermal analysis). Morphological investigation highlighted that the sample is composed of long fibers (> 5 µm) with a significant fraction (ca. 55%) having width below 0.25 µm, considered the most biologically active fibers. Moreover, the crystal chemical characterization showed that Fe occurs at the octahedral sites of the tremolite structure. It should be noted that Fe plays a primary role in the toxicity of asbestos. Based on these results, the investigated asbestos tremolite may be considered a potent mesothelial carcinogen, requiring therefore special attention for public health protection purposes. Investigations using sentinel animals to assess the diffusion of the tremolite fibers into the environment from the serpentinite rocks and soils of Iacolinei quarry are in progress.}, } @article {pmid39312698, year = {2024}, author = {Khosla, D and Singh, PK and Chhabria, BA and Kataria, V and Singh, N and Kapoor, R}, title = {Malignant pleural mesothelioma: The disdained member of thoracic oncology!.}, journal = {World journal of experimental medicine}, volume = {14}, number = {3}, pages = {91739}, pmid = {39312698}, issn = {2220-315X}, abstract = {Pleural mesothelioma is a very aggressive malignancy that arises from the pleural mesothelial cell lining and is linked strongly to prior asbestos exposure. The ban on asbestos has helped to lower the incidence, but in developing countries like India, it is expected to rise. It has an extended latency period usually progressing over decades and presents with nonspecific symptoms. It has a median survival ranging between 10-22 months. The diagnosis of malignant pleural mesothelioma is challenging and is done using computed tomography (CT), magnetic resonance imaging, or positron emission tomography-CT, with the last two predicting the resectability of the tumor better than CT alone. A pleural biopsy along with an array of immunohistochemical markers, such as p16, BRCA1 associated protein 1, and claudin-4, are required for a definitive diagnosis. Several genetic alterations have prognostic significance as well. The current histological subtype identification is indispensable for decision making because of the new therapeutic avenues being explored. The combination of nivolumab and ipilimumab-based immunotherapy outperformed platinum and pemetrexed-based chemotherapy in terms of survival benefit and improved quality of life especially for non-epithelioid subtypes. However, the latter continues to be a robust treatment option for patients with the epithelioid subtype. Surgery is recommended for resectable cases with radiotherapy being indicated in neoadjuvant, adjuvant, and palliative settings along with systemic treatment. This review article provides an overview of epidemiology, etiology, clinical manifestations, diagnostic approaches (including immunohistochemical and genetic markers), staging, and multidisciplinary approaches to current treatment for malignant pleural mesothelioma using surgery, chemotherapy, immunotherapy, and radiotherapy. It also sheds light on some recent studies (EMPHACIS, CALGB30901, Checkmate-743, etc.) that have led to significant developments in recent years with clinically meaningful results.}, } @article {pmid39290927, year = {2024}, author = {Reddy, S and M G, K and Gattu, R and P, A and Kuthadi, M}, title = {Challenging the Norm: Occurrence of Synchronous Pleural and Peritoneal Mesothelioma in a Female Patient.}, journal = {Cureus}, volume = {16}, number = {8}, pages = {e67118}, pmid = {39290927}, issn = {2168-8184}, abstract = {Here, we present a unique case involving a female patient in her 40s with synchronous malignant pleural and peritoneal mesothelioma, despite lacking a history of asbestos exposure. The patient's initial symptoms included dyspnoea, chest pain, cough, fever, appetite loss, and weight loss over a month. Clinical evaluation led to the identification of right-sided pleural effusion, prompting consideration of differential diagnoses, such as tubercular or malignant pleural effusion. A thoracoscopy-guided biopsy, followed by histopathological examination and immunohistochemical staining, confirmed the diagnosis of mesothelioma. Chemotherapy was initiated as part of the treatment plan. The prognosis for this condition is generally bad; however, unusual cases of extended survival have been documented. The complexities of our case underscore the critical necessity for a thorough and aggressive evaluation of pleural effusion cases to unveil rare underlying causes, such as mesothelioma.}, } @article {pmid39281715, year = {2024}, author = {Huang, Q and Chen, Y and Lian, L and Lei, Q and Chen, J and Wu, L and Hemminki, K and Ji, J and Chen, T}, title = {Burden of malignant mesothelioma in China during 1990-2019 and the projections through 2029.}, journal = {Journal of the National Cancer Center}, volume = {4}, number = {3}, pages = {214-222}, pmid = {39281715}, issn = {2667-0054}, abstract = {OBJECTIVE: To provide the most up-to-date data on the burden of malignant mesothelioma (MM) and the projections through 2029 in China.

METHODS: Data on patients diagnosed with MM from China during 1990-2019 were obtained from the Global Burden of Disease (GBD) 2019 database, including annual cases and deaths data and age-standardized rates of incidence, mortality, and disability-adjusted life-years (DALYs) associated with MM among different age groups. Temporal trends during 1990-2019 were analyzed by the Joinpoint regression models using 95% confidence interval (CI), while the projections through 2029 were calculated by the Bayesian age-period-cohort model. Data on the production and consumption of asbestos in China were obtained from the United States Geological Survey on Mineral Commodity Summaries during 1996-2023.

RESULTS: We observed a significant elevation in incident new cases and deaths over the last 3 decades, increasing from 1193 in 1990 to 2815 in 2019 for incident cases and from 1134 in 1990 to 2773 in 2019 for death cases. We found a roughly 6% increase in the proportion of incident cases for those aged >70 years (30% in 2019 versus 24% in 1990), while for the proportion of deaths similar elevation for those aged >70 years was found. Additionally, men had significantly higher DALYs due to MM across age groups compared with women. Asbestos consumption in China dramatically dropped since 2012 and reached the bottom in 2017 with 230 kilotons. By 2029, the projected age-standardized rate for incidence and mortality is expected to reach 1.2 per million for both.

CONCLUSION: We found, for the first time using GBD data on the Chinese population, that the burden of MM has been significantly increasing in China over the last three decades and will continue to increase in the upcoming decade, suggesting an urgent need for a complete ban on chrysotile asbestos in China.}, } @article {pmid39269499, year = {2024}, author = {Sheema, AN and Naiki-Ito, A and Kakehashi, A and Ahmed, OHM and Alexander, DB and Alexander, WT and Numano, T and Kato, H and Goto, Y and Takase, H and Hirose, A and Wakahara, T and Miyazawa, K and Takahashi, S and Tsuda, H}, title = {Fullerene and fullerene whisker are not carcinogenic to the lungs and pleura in rat long-term study after 2-week intra-tracheal intrapulmonary administration.}, journal = {Archives of toxicology}, volume = {}, number = {}, pages = {}, pmid = {39269499}, issn = {1432-0738}, support = {JPMH20316858//Ministry of Health, Labour and Welfare/ ; JPMH16769893//Ministry of Health, Labour and Welfare/ ; }, abstract = {Fullerene whiskers (FLW)s are thin rod-like structures composed of C60 and C70 fullerene (FL). The shape of FLWs suggests potential toxic effects including carcinogenicity to the lung and pleura, similar to effects elicited by asbestos and multi-walled carbon nanotubes (MWCNT)s. However, no long-term carcinogenic studies of FL or FLW have been conducted. In the present study we investigated the pulmonary and pleural carcinogenicity of FL and FLW. Twelve-week-old male F344 rats were administered 0.25 or 0.5 mg FL, FLW, MWCNT-7, and MWCNT-N by intra-tracheal intra-pulmonary spraying (TIPS). Acute lung lesions and carcinogenicity were analyzed at 1 and 104 weeks after 8 doses/15 days TIPS administration. At week 1, FLW, MWCNT-7, and MWCNT-N significantly increased alveolar macrophage infiltration. Expression of Ccl2 and Ccl3, reactive oxygen species production, and cell proliferation were significantly increased by administration of MWCNT-7 and MWCNT-N but not FL or FLW. At week 104, the incidence of bronchiolo-alveolar adenoma plus adenocarcinoma was significantly increased in the MWCNT-7 and MWCNT-N groups, and the incidence of mesothelioma was significantly increased in the MWCNT-7 group. No significant induction of pulmonary or pleural tumorigenesis was observed in the FL or FLW groups. The number of 8-OHdG-positive cells in the alveolar epithelium was significantly increased in the MWCNT-7 and MWCNT-N groups but not in the FL or FLW groups. FL and FLW did not exert pulmonary or pleural carcinogenicity in our study. In addition, oxidative DNA damage was implicated in MWCNT-induced lung carcinogenesis, suggesting that it may be a useful initial marker of carcinogenicity.}, } @article {pmid39265763, year = {2024}, author = {Feng, L and Li, T and Xu, B and Huang, J and Xia, H and Jiang, Z and Chen, J and Pan, S and Zhang, X and Jiang, H and Lou, J}, title = {Integrated DNA methylation analysis of peripheral blood from asbestos exposed populations and patients with malignant mesothelioma reveals novel methylation driver genes of diagnostic and prognostic relevance.}, journal = {Environmental pollution (Barking, Essex : 1987)}, volume = {362}, number = {}, pages = {124928}, doi = {10.1016/j.envpol.2024.124928}, pmid = {39265763}, issn = {1873-6424}, abstract = {Effective biomarkers are paramount importance for the early detection and prognosis prediction of malignant mesothelioma (MM) which mainly caused by asbestos exposure, and DNA methylation has been demonstrated to be a potentially powerful diagnostic tool. To elucidate the relationship between asbestos exposure and alterations in DNA methylation patterns, as well as the potential diagnostic and prognostic value of differentially methylated regions and CpG sites (DMRs/DMCs) in the progression of MM. The current study employed reduced representation bisulfite sequencing (RRBS) to examine the genome-wide DNA methylation profiles in the peripheral blood of individuals exposed to asbestos and those diagnosed with MM, in comparison to the controls, and DMRs/DMCs were subsequently validated by targeted bisulfite sequencing (TBS). Our results suggested that there were 12 DMRs/DMCs exhibiting a consistent change trend of DNA methylation in both RRBS and TBS results. Significant correlations were observed between DNA methylation levels of DMRs/DMCs and the duration of occupational asbestos exposure. The evaluation of the receiver operating characteristic (ROC) curve suggested that the DNA methylation status of FHIT, CCR12P and CDH15 may serve as diagnosis indicator in distinguishing MM patients from healthy controls and those exposed to asbestos. Our findings offer a foundation for the role of DNA methylation in the development of MM induced by asbestos exposure. The potential significance of FHIT, CCR12P and CDH15 DNA methylation alterations in the pathogenesis and advancement of MM disease suggests their potential as diagnostic and prognostic biomarkers.}, } @article {pmid39258522, year = {2024}, author = {Kinsman, N and Del Monaco, A and Dimitriadis, C and Xie, S and Benke, G and Sim, MR and Walker-Bone, K}, title = {Bauxite mine and alumina refinery workers: mortality and cancer risk.}, journal = {Occupational medicine (Oxford, England)}, volume = {74}, number = {7}, pages = {508-513}, pmid = {39258522}, issn = {1471-8405}, support = {//Alcoa of Australia Ltd/ ; }, mesh = {Humans ; Male ; Female ; *Occupational Exposure/adverse effects ; *Aluminum Oxide/adverse effects ; *Occupational Diseases/mortality/epidemiology ; Australia/epidemiology ; *Mining/statistics & numerical data ; Middle Aged ; *Neoplasms/mortality/epidemiology ; Adult ; Incidence ; Risk Factors ; Mesothelioma/mortality/epidemiology ; Aged ; Melanoma/mortality/epidemiology ; Metallurgy ; Prostatic Neoplasms/mortality/epidemiology ; }, abstract = {BACKGROUND: Aluminium industry workers are at risk of long-term health consequences.

AIMS: To investigate mortality and cancer incidence in bauxite mine and alumina refinery workers.

METHODS: A pre-existing cohort of workers was re-linked with the Australian National Death Index, and the Australian Cancer Database to provide additional death (7 years) and cancer (9 years) data. Standardized mortality ratios (SMRs) and standardized incidence rates (SIRs) were estimated by job category, duration of employment and time since first employment.

RESULTS: Linkage was performed for 6935 (6207 male) workers. Compared with the general population, there was a reduced or similar risk of death for mine/refinery workers for all causes except mesothelioma which was increased amongst male production workers [SMR 2.42, 95% CI 1.11-4.60]. Mesothelioma incidence was also increased amongst males [SIR 2.50, 95% CI 1.60-3.71]. Male office workers had a greater incidence of prostate cancer [SIR 1.30, 95% CI 1.06-1.57] and thyroid cancer [SIR 3.47, 95% CI 1.66-6.38]. Melanoma incidence was increased in female office workers [SIR 2.27, 95% CI 1.36-3.54]. Lip cancer incidence was increased in male maintenance/production workers [SIR 2.04, 95% CI 1.02-3.65]. Overall cancer incidence was otherwise similar to the general Australian population.

CONCLUSIONS: Overall risk of death and incidence of cancer for bauxite mine and alumina refinery workers was similar to the general population. Incidence and risk of death from mesothelioma were higher, likely due to historic asbestos exposure in this and other industries. The increased risk of melanoma, lip, prostate and thyroid cancers requires further investigation.}, } @article {pmid39237806, year = {2024}, author = {Duraffour, F and Ramos-Bonilla, JP and Lysaniuk, B}, title = {Use of agent-based modeling to analyze potential non-occupational exposures to asbestos of the general population of Sibaté (Colombia).}, journal = {Environmental monitoring and assessment}, volume = {196}, number = {10}, pages = {900}, pmid = {39237806}, issn = {1573-2959}, support = {ANR-18-CE03-0001-01//Agence Nationale de la Recherche/ ; ANR-18-CE03-0001-01//Agence Nationale de la Recherche/ ; ANR-18-CE03-0001-01//Agence Nationale de la Recherche/ ; }, mesh = {*Asbestos/analysis ; Humans ; *Environmental Exposure/statistics & numerical data ; Environmental Monitoring/methods ; Mesothelioma/epidemiology/chemically induced ; }, abstract = {Previous studies conducted in the municipality of Sibaté (Colombia) have revealed alarming findings regarding asbestos exposure in the region, as it is the site of the country's first mesothelioma cluster. Non-occupational asbestos exposure events were identified in this population, and the young age of the mesothelioma cases at the time of diagnosis suggests that asbestos exposure occurred during their childhood. The creation of landfilled zones in the 1980s and 1990s, utilizing friable asbestos among other disposed materials, may have been a significant asbestos exposure event contributing to the elevated number of mesothelioma cases. The objective of this study was to model various historical exposure scenarios related to the creation and interaction of the population with asbestos-contaminated landfilled zones, in light of the absence of asbestos monitoring in the region. The models utilized a multi-agent simulation process, focusing on a 10-year period (1986-1995). Various relevant variables were incorporated into the modeling process, including, for example, the number of children playing in the landfilled zones and the percentage of children carrying asbestos fibers on their clothes to their homes. A range of values for input data for the models were utilized, spanning from very conservative numbers to exposure-promoting values. The average number of exposed individuals estimated over 750 simulation runs, considering all scenarios, was 571, with a range between 31 and 3800 exposed individuals. The use of multi-agent simulation models can assist the understanding of past asbestos exposure events, especially when there is a lack of environmental surveillance data.}, } @article {pmid39204360, year = {2024}, author = {Favaron, C and Gaiaschi, L and Casali, C and De Luca, F and Gola, F and Cavallo, M and Ramundo, V and Aldieri, E and Milanesi, G and Visonà, SD and Ravera, M and Bottone, MG}, title = {Unraveling Novel Strategies in Mesothelioma Treatments Using a Newly Synthetized Platinum(IV) Compound.}, journal = {Pharmaceutics}, volume = {16}, number = {8}, pages = {}, pmid = {39204360}, issn = {1999-4923}, support = {FRG Fondo ricerca e Giovani Maria Grazia Bottone//University of Pavia: Fondi Ricerca Giovani (FRG 2021)./ ; }, abstract = {Malignant mesothelioma is a rare tumor associated with asbestos exposure. Mesothelioma carcinogenesis is related to enhanced reactive oxygen species (ROS) production and iron overload. Despite the recent advances in biomedical sciences, to date the only available treatments include surgery in a small fraction of patients and platinum-based chemotherapy in combination with pemetrexed. In this view, the purpose of this study was to evaluate the therapeutic potential of the newly synthetized platinum prodrug Pt(IV)Ac-POA compared to cisplatin (CDDP) on human biphasic mesothelioma cell line MSTO-211H using different complementary techniques, such as flow-cytometry, transmission electron microscopy (TEM), and immunocytochemistry. Healthy mesothelial cell lines Met-5A were also employed to assess the cytotoxicity of the above-mentioned compounds. Our in vitro results showed that Pt(IV)Ac-POA significantly interfere with iron metabolisms and more importantly is able to trigger cell death, through different pathways, including ferroptosis, necroptosis, and apoptosis, in neoplastic cells. On the other hand, CDDP triggers mainly apoptotic and necrotic cell death. In conclusion, Pt(IV)Ac-POA may represent a new promising pharmacological agent in the treatment of malignant mesothelioma.}, } @article {pmid39189372, year = {2024}, author = {Giacomino, F and Marinelli, F and Bisceglia, I and Cacchi, M and Storchi, C and Pinto, C and Mangone, L and Romanelli, A and Morabito, F}, title = {Trends in Asbestos Exposure and Malignant Mesothelioma Incidence in Emilia-Romagna Italy: A Retrospective Study 1996-2023.}, journal = {La Medicina del lavoro}, volume = {115}, number = {4}, pages = {e2024028}, pmid = {39189372}, issn = {0025-7818}, mesh = {Humans ; Italy/epidemiology ; Male ; Retrospective Studies ; Female ; *Asbestos/adverse effects ; Aged ; *Mesothelioma, Malignant/epidemiology ; Incidence ; *Occupational Exposure/statistics & numerical data/adverse effects ; Middle Aged ; *Lung Neoplasms/epidemiology/etiology ; *Mesothelioma/epidemiology/etiology ; Environmental Exposure/adverse effects/statistics & numerical data ; Adult ; Aged, 80 and over ; Occupational Diseases/epidemiology ; }, abstract = {Malignant mesothelioma (MM) is a rare but lethal cancer strongly associated with asbestos exposure. This retrospective study examines trends in asbestos exposure in Emilia-Romagna, Northern Italy. Between 1996 and 2023, 3,513 cases of MM were recorded, predominantly in males (72%) and in older than 65 years (79%). Occupational exposure accounted for 82% of cases, with a significant increase observed over time from 71% to 88% in the most recent period. A greater definition of professional exposure indicates that certain exposure has gone from 49% in the first period to 62% and 58% in the last two periods; probable exposure showed a decrease from 21% to 16% while possible exposure decreased from 16% to 13%. Familiar exposure remained relatively constant at around 8%, environmental exposure showed a slight decrease from 4% to 2%, while non-occupational exposure remained stable at 2%. Among patients with exclusively occupational exposure (1,826 cases), 87% were male and aged between 65 and 75 years (36%) and 75+ (41%). The exposure rates for the province of residence see the province of Reggio Emilia with the highest occupational exposure rate (2.5 x 100,000 residents), followed by Ravenna (2.3 x 100,000 residents) and Parma and Piacenza which have similar exposure rates with 2.2 x 100,000 residents. Professional sectors such as construction, railway maintenance and metalworking are identified as high-risk industries. Despite efforts to mitigate exposure, non-occupational and environmental exposures persist. The study highlights the importance of continuous surveillance and exposure monitoring to guide effective interventions and legal recognition of MM.}, } @article {pmid39181447, year = {2024}, author = {Kindler, HL and Rosenthal, A and Giroux, DJ and Nowak, AK and Billè, A and Gill, RR and Pass, H and Rice, D and Ripley, RT and Wolf, A and Blyth, KG and Cedres, S and Rusch, V and , }, title = {The International Association for the Study of Lung Cancer Mesothelioma Staging Project: Proposals for the M Descriptors in the Forthcoming Ninth Edition of the TNM Classification for Pleural Mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jtho.2024.08.022}, pmid = {39181447}, issn = {1556-1380}, abstract = {INTRODUCTION: The International Association for the Study of Lung Cancer developed a global multicenter database to propose evidence-based revisions for the ninth edition of the TNM classification of pleural mesothelioma (PM). This study analyzes the M category to validate eighth edition M category recommendations.

METHODS: Cases were submitted electronically or by transfer of existing institutional databases for patients with histologically or cytologically confirmed PM. The presence and number of metastases (single versus multiple) in each of eight organ systems were reported for patients with M1 disease at diagnosis. Overall survival (OS) was calculated by the Kaplan-Meier method. Differences in OS were assessed by log-rank test.

RESULTS: Of 7338 submitted cases, 3598 were eligible and 3221 had sufficient data for clinical staging; 228 cases (7%) were M1. Median overall estimated survival was inferior for M1 compared with M0 patients: 10.5 months versus 21.5 months, respectively (p < 0.0001); estimated 1-year survival was 46% versus 71%, respectively. OS differences between M categories were preserved within histologic subgroups. Among 158 patients with organ-specific documentation of M1 disease, there was no statistically significant difference in OS between those with intrathoracic versus more distant metastatic disease (14.4 mo versus 10.9 mo, p = 0.64). No significant survival difference was detected between patients with metastatic disease in a single-organ system versus multiple-organ systems (12.6 mo versus 8.8 mo, p = 0.45).

CONCLUSIONS: This evidence-based analysis of the M category for PM conforms with the eighth edition M descriptors. No changes are proposed in the ninth edition of the mesothelioma M category.}, } @article {pmid39168966, year = {2024}, author = {Zhang, M and Bzura, A and Baitei, EY and Zhou, Z and Spicer, JB and Poile, C and Rogel, J and Branson, A and King, A and Barber, S and Kamata, T and Dzialo, J and Harber, J and Greystoke, A and Nusrat, N and Faulkner, D and Sun, Q and Nolan, L and Hahne, JC and Scotland, M and Walter, H and Darlison, L and Morgan, B and Bajaj, A and Brookes, C and Hollox, EJ and Lubawska, D and Jama, M and Griffiths, G and Nakas, A and Kutywayo, K and Luo, JL and Klampatsa, A and Cooper, A and Halder, K and Wells-Jordan, P and Zhou, H and Dudbridge, F and Thomas, A and Richards, CJ and Pritchard, C and Yang, H and Barer, M and Fennell, DA}, title = {A gut microbiota rheostat forecasts responsiveness to PD-L1 and VEGF blockade in mesothelioma.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {7187}, pmid = {39168966}, issn = {2041-1723}, support = {C10604/A25151//Cancer Research UK (CRUK)/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Bevacizumab/therapeutic use/pharmacology ; Male ; *B7-H1 Antigen/metabolism/antagonists & inhibitors ; *Antibodies, Monoclonal, Humanized/therapeutic use ; Female ; *Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; Middle Aged ; Aged ; Mesothelioma, Malignant/drug therapy ; Vascular Endothelial Growth Factor A/metabolism ; Mesothelioma/immunology/drug therapy/microbiology/pathology ; Tumor Microenvironment/immunology ; Lung Neoplasms/drug therapy/immunology/pathology/genetics/microbiology ; Treatment Outcome ; }, abstract = {Malignant mesothelioma is a rare tumour caused by asbestos exposure that originates mainly from the pleural lining or the peritoneum. Treatment options are limited, and the prognosis is dismal. Although immune checkpoint blockade (ICB) can improve survival outcomes, the determinants of responsiveness remain elusive. Here, we report the outcomes of a multi-centre phase II clinical trial (MiST4, NCT03654833) evaluating atezolizumab and bevacizumab (AtzBev) in patients with relapsed mesothelioma. We also use tumour tissue and gut microbiome sequencing, as well as tumour spatial immunophenotyping to identify factors associated with treatment response. MIST4 met its primary endpoint with 50% 12-week disease control, and the treatment was tolerable. Aneuploidy, notably uniparental disomy (UPD), homologous recombination deficiency (HRD), epithelial-mesenchymal transition and inflammation with CD68[+] monocytes were identified as tumour-intrinsic resistance factors. The log-ratio of gut-resident microbial genera positively correlated with radiological response to AtzBev and CD8[+] T cell infiltration, but was inversely correlated with UPD, HRD and tumour infiltration by CD68[+] monocytes. In summary, a model is proposed in which both intrinsic and extrinsic determinants in mesothelioma cooperate to modify the tumour microenvironment and confer clinical sensitivity to AtzBev. Gut microbiota represent a potentially modifiable factor with potential to improve immunotherapy outcomes for individuals with this cancer of unmet need.}, } @article {pmid39163890, year = {2024}, author = {Little, LD and Barnett, SE and Issitt, T and Bonsall, S and Carolan, VA and Allen, E and Cole, LM and Cross, NA and Coulson, JM and Haywood-Small, SL}, title = {Volatile organic compound analysis of malignant pleural mesothelioma chorioallantoic membrane xenografts.}, journal = {Journal of breath research}, volume = {18}, number = {4}, pages = {}, pmid = {39163890}, issn = {1752-7163}, mesh = {*Volatile Organic Compounds/analysis ; *Chorioallantoic Membrane ; Animals ; Humans ; *Mesothelioma, Malignant/pathology ; *Gas Chromatography-Mass Spectrometry ; *Pleural Neoplasms/pathology ; *Lung Neoplasms/pathology/metabolism ; Biomarkers, Tumor/analysis ; Mesothelioma/pathology ; Cell Line, Tumor ; Heterografts ; Breath Tests/methods ; Solid Phase Microextraction/methods ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive cancer associated with asbestos exposure. MPM is often diagnosed late, at a point where limited treatment options are available, but early intervention could improve the chances of successful treatment for MPM patients. Biomarkers to detect MPM in at-risk individuals are needed to implement early diagnosis technologies. Volatile organic compounds (VOCs) have previously shown diagnostic potential as biomarkers when analysed in MPM patient breath. In this study, chorioallantoic membrane (CAM) xenografts of MPM cell lines were used as models of MPM tumour development for VOC biomarker discovery with the aim of generating targets for investigation in breath, biopsies or other complex matrices. VOC headspace analysis of biphasic or epithelioid MPM CAM xenografts was performed using solid-phase microextraction and gas chromatography-mass spectrometry. We successfully demonstrated the capture, analysis and separation of VOC signatures from CAM xenografts and controls. A panel of VOCs was identified that showed discrimination between MPM xenografts generated from biphasic and epithelioid cells and CAM controls. This is the first application of the CAM xenograft model for the discovery of VOC biomarkers associated with MPM histological subtypes. These findings support the potential utility of non-invasive VOC profiling from breath or headspace analysis of tissues for detection and monitoring of MPM.}, } @article {pmid39143249, year = {2024}, author = {Mayoral, M and Araujo-Filho, JAB and Tan, KS and Ortiz, E and Adusumilli, PS and Rusch, V and Zauderer, M and Ginsberg, MS}, title = {Are there features that can predict the unresectability of pleural mesothelioma?.}, journal = {European radiology}, volume = {}, number = {}, pages = {}, pmid = {39143249}, issn = {1432-1084}, abstract = {INTRODUCTION: The current clinical staging of pleural mesothelioma (PM) is often discordant with the pathologic staging. This study aimed to identify clinical and radiological features that could help predict unresectability in PM.

METHODS: Twenty-two descriptive radiologic features were retrospectively evaluated on preoperative computed tomography (CT) and/or positron emission tomography/CT (PET/CT) performed in patients with presumably resectable PM who underwent surgery. Measurements of maximum and sum pleural thickness at three levels of the thorax (upper, middle, and lower) were taken and stratified based on the cutpoints provided by the International Association for the Study of Lung Cancer (IASLC). Clinical and radiological features, including clinical-stage, were compared between resectable and unresectable tumors by univariate analysis and logistic regression modeling.

RESULTS: Of 133 patients, 69/133 (52%) had resectable and 64/133 (48%) had unresectable PM. Asbestos exposure (p = 0.005), neoadjuvant treatment (p = 0.001), clinical T-stage (p < 0.0001), all pleural thickness measurements (p < 0.05), pleural thickness pattern (p < 0.0001) and degree (p = 0.033), lung invasion (p = 0.004), extrapleural space obliteration (p < 0.0001), extension to subphrenic space (p = 0.0004), and two combination variables representing extensive diaphragmatic contact and/or chest wall involvement (p = 0.002) and mediastinal invasion (p < 0.0001) were significant predictors at univariate analysis. At multivariable analysis, all models achieved a strong diagnostic performance (area under the curve (AUC) > 0.8). The two best-performing models were one that included the upper-level maximum pleural thickness, extrapleural space obliteration, and mediastinal infiltration (AUC = 0.876), and another that integrated clinical variables and radiological assessment through the clinical T-stage (AUC = 0.879).

CONCLUSION: Selected clinical and radiologic features, including pleural thickness measurements, appear to be strong predictors of unresectability in PM.

CLINICAL RELEVANCE STATEMENT: A more accurate prediction of unresectability in the preoperative assessment of patients with pleural mesothelioma may avoid unnecessary surgery and prompt initiation of nonsurgical treatments.

KEY POINTS: About half of pleural mesothelioma patients are reported to receive an incorrect disease stage preoperatively. Eleven features identified as predictors of unresectability were included in strongly performing predictive models. More accurate preoperative staging will help clinicians and patients choose the most appropriate treatments.}, } @article {pmid39138009, year = {2024}, author = {Nash, J and Stone, E and Vinod, S and Leong, T and Dawkins, P and Stirling, RG and Harden, S and Bolton, A and McWilliams, A and O'Byrne, K and Wright, GM and Brunelli, VN and Guan, T and Philpot, S and Navani, N and Brims, F and , }, title = {Lung cancer (internet-based) Delphi (LUCiD): A modified eDelphi consensus process to establish Australasian clinical quality indicators for thoracic cancer.}, journal = {Respirology (Carlton, Vic.)}, volume = {}, number = {}, pages = {}, doi = {10.1111/resp.14812}, pmid = {39138009}, issn = {1440-1843}, abstract = {BACKGROUND AND OBJECTIVE: Approximately 16,000 new cases of lung cancer are diagnosed each year in Australia and Aotearoa New Zealand, and it is the leading cause of cancer death in the region. Unwarranted variation in lung cancer care and outcomes has been described for many years, although clinical quality indicators to facilitate benchmarking across Australasia have not been established. The purpose of this study was to establish clinical quality indicators applicable to lung and other thoracic cancers across Australia and Aotearoa New Zealand.

METHODS: Following a literature review, a modified three round eDelphi consensus process was completed between October 2022 and June 2023. Participants included clinicians from all relevant disciplines, patient advocates, researchers and other stakeholders, with representatives from all Australian states and territories and Aotearoa New Zealand. Consensus was set at a threshold of 70%, with the first two rounds conducted as online surveys, and the final round held as a hybrid in person and virtual consensus meeting.

RESULTS: The literature review identified 422 international thoracic oncology indicators, and a total of 71 indicators were evaluated over the course of the Delphi consensus. Ultimately, 27 clinical quality indicators reached consensus, covering the continuum of thoracic oncologic care from diagnosis to first line treatment. Indicators benchmarking supportive care were poorly represented. Attendant numeric quality standards were developed to facilitate benchmarking.

CONCLUSION: Twenty-seven clinical quality indicators relevant to thoracic oncology care in Australasia were developed. Real world implementation will now be explored utilizing a prospective dataset collected across Australia.}, } @article {pmid39133306, year = {2024}, author = {Thunold, S and Hernes, E and Farooqi, S and Öjlert, ÅK and Francis, RJ and Nowak, AK and Szejniuk, WM and Nielsen, SS and Cedres, S and Perdigo, MS and Sørensen, JB and Meltzer, C and Mikalsen, LTG and Helland, Å and Malinen, E and Haakensen, VD}, title = {Outcome prediction based on [18F]FDG PET/CT in patients with pleural mesothelioma treated with ipilimumab and nivolumab +/- UV1 telomerase vaccine.}, journal = {European journal of nuclear medicine and molecular imaging}, volume = {}, number = {}, pages = {}, pmid = {39133306}, issn = {1619-7089}, support = {2020077//Helse Sør-Øst RHF/ ; 2021083//Helse Sør-Øst RHF/ ; }, abstract = {PURPOSE: The introduction of immunotherapy in pleural mesothelioma (PM) has highlighted the need for effective outcome predictors. This study explores the role of [18F]FDG PET/CT in predicting outcomes in PM treated with immunotherapy.

METHODS: Patients from the NIPU trial, receiving ipilimumab and nivolumab +/- telomerase vaccine in second-line, were included. [18F]FDG PET/CT was obtained at baseline (n = 100) and at week-5 (n = 76). Metabolic tumour volume (MTV) and peak standardised uptake value (SUVpeak) were evaluated in relation to survival outcomes. Wilcoxon rank-sum test was used to assess differences in MTV, total lesion glycolysis (TLG), maximum standardised uptake value (SUVmax) and SUVpeak between patients exhibiting an objective response, defined as either partial response or complete response according to the modified Response Criteria in Solid Tumours (mRECIST) and immune RECIST (iRECIST), and non-responders, defined as either stable disease or progressive disease as their best overall response.

RESULTS: Univariate Cox regression revealed significant associations of MTV with OS (HR 1.36, CI: 1.14, 1.62, p < 0.001) and PFS (HR 1.18, CI: 1.03, 1.34, p = 0.02), while multivariate analysis showed a significant association with OS only (HR 1.35, CI: 1.09, 1.68, p = 0.007). While SUVpeak was not significantly associated with OS or PFS in univariate analyses, it was significantly associated with OS in multivariate analysis (HR 0.43, CI: 0.23, 0.80, p = 0.008). Objective responders had significant reductions in TLG, SUVmax and SUVpeak at week-5.

CONCLUSION: MTV provides prognostic value in PM treated with immunotherapy. High SUVpeak was not associated with inferior outcomes, which could be attributed to the distinct mechanisms of immunotherapy. Early reductions in PET metrics correlated with treatment response.

STUDY REGISTRATION: The NIPU trial (NCT04300244) is registered at clinicaltrials.gov. https://classic.

CLINICALTRIALS: gov/ct2/show/NCT04300244?cond=Pleural+Mesothelioma&cntry=NO&draw=2&rank=4.}, } @article {pmid39129543, year = {2024}, author = {Delhaise, J and Gustin, M}, title = {[Erionite, an exposure factor linked to pleural mesothelioma].}, journal = {Revue medicale de Liege}, volume = {79}, number = {7-8}, pages = {478-484}, pmid = {39129543}, issn = {0370-629X}, mesh = {Humans ; *Pleural Neoplasms/etiology/diagnosis ; *Mesothelioma/etiology/chemically induced ; Male ; Zeolites/adverse effects ; Environmental Exposure/adverse effects ; Mesothelioma, Malignant/pathology ; }, abstract = {Mesotheliomas are neoplasia developed from the mesothelium, a layer covering the viscera (visceral layer) and the cavity where the organs are (parietal layer). The best known, and the most frequently encountered is the pleural mesothelioma. This disease has a close link with exposure to asbestos, a mineral fibre now banned in several countries. However, other exposure factors have also been incriminated, including another one recognised as a certain carcinogenic agent for several years now : erionite. We present the case of a patient with pleural mesothelioma whose exposure to erionite could be demonstrated. The presentation of this clinical case will be complemented by a literature review on this less known and mostly environmental exposure, contrary to asbestos which is mostly professional.}, } @article {pmid39114201, year = {2024}, author = {Al-Moussally, F and Alamin, F and Khan, S and Gopalan, PK}, title = {Sarcomatoid Mesothelioma With New Pancreatic Lesions Presenting As Acute Pancreatitis: A Case Report.}, journal = {Cureus}, volume = {16}, number = {7}, pages = {e64088}, pmid = {39114201}, issn = {2168-8184}, abstract = {Sarcomatoid mesothelioma is a rare, aggressive malignancy that usually follows asbestos exposure. It is the least common subtype of mesotheliomas, following epithelial and biphasic subtypes. Pleural mesothelioma can metastasize, with the liver, kidneys, adrenal glands, and opposite lungs being the most commonly reported sites for metastasis. Metastasis of the pancreas is extremely rare, which is why the authors of this case report intend to present the case of a 78-year-old male who was found to have acute pancreatitis, most likely secondary to metastatic lesions.}, } @article {pmid39111017, year = {2024}, author = {Otte, N and Fraune, E and Cetiner, Y and Felten, MK and Dirrichs, T and Krabbe, J and Kraus, T}, title = {Asbestos Surveillance Program Aachen (ASPA): Cancer mortality among asbestos exposed power industry workers.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {195}, number = {}, pages = {107899}, doi = {10.1016/j.lungcan.2024.107899}, pmid = {39111017}, issn = {1872-8332}, mesh = {Humans ; *Occupational Exposure/adverse effects ; *Asbestos/adverse effects ; Male ; *Lung Neoplasms/mortality/etiology/epidemiology ; Middle Aged ; Female ; Aged ; Adult ; Mesothelioma/mortality/etiology ; Occupational Diseases/mortality/epidemiology ; Follow-Up Studies ; }, abstract = {BACKGROUND: The time between initial asbestos exposure and asbestos-related disease can span several decades. The Asbestos Surveillance Program aims to detect early asbestos-related diseases in a cohort of 8,565 power industry workers formerly exposed to asbestos.

RESEARCH QUESTION: How does asbestos exposure patterns affect cancer mortality and the duration of latency until death?

METHODS: A mortality follow-up was conducted with available vital status for 8,476 participants (99 %) and available death certificates for 89.9 % of deceased participants. Standardised mortality ratios (SMR) were calculated for asbestos-related cancers. The SMR of mesothelioma and lung cancer were stratified by exposure duration, cumulative asbestos exposure and smoking. The effect of age at first exposure, cumulative asbestos exposure and smoking on the duration of latency until death was examined using multiple linear regression analysis.

RESULTS: The mortality risk of mesothelioma (n = 104) increased with cumulative asbestos exposure but not with exposure duration; the highest mortality (SMR: 23.20; 95 % CI: 17.62-29.99) was observed in participants who performed activities with short extremely high exposures (steam turbine revisions). Lung cancer mortality (n = 215) was not increased (SMR: 1.03; 95 % CI: 0.89-1.17). Median latency until death was 46 (15-63) years for mesothelioma and 44 (15-70) years for lung cancer and deaths occurred between age 64 and 82 years. Latency until death was not influenced by age at first exposure, cumulative exposure, or smoking.

CONCLUSION: Cumulative dose seems to be more appropriate than exposure duration for estimating the risk of mesothelioma death. Additionally, exposure with high cumulative doses in short time should be considered. Since only lung cancer mortality, not incidence, was recorded in this study, lung cancer risk associated with asbestos exposure could not be assessed and the lung cancer mortality was lower than expected probably due to screening effects and improved treatments. The critical time window of death from asbestos-related cancer is between the seventh and ninth decade of life. Future studies should further explore the concept of latency, especially since large ranges are reported throughout the literature.}, } @article {pmid39083122, year = {2024}, author = {Kraus, T and Jonigk, D}, title = {[Mesothelioma-30 years after the asbestos ban in Germany].}, journal = {Pathologie (Heidelberg, Germany)}, volume = {45}, number = {5}, pages = {305-308}, pmid = {39083122}, issn = {2731-7196}, mesh = {Humans ; Germany/epidemiology ; *Asbestos/adverse effects ; *Mesothelioma/epidemiology/history/etiology ; Occupational Diseases/epidemiology/history/prevention & control ; Occupational Exposure/legislation & jurisprudence/history/adverse effects/prevention & control ; Incidence ; Pleural Neoplasms/epidemiology/history/etiology ; Asbestosis/epidemiology/history/prevention & control/etiology ; }, abstract = {In 1993, a total asbestos ban was introduced in Germany. Thirty years later, mesothelioma is still one of the most frequent occupational diseases. Recent data on incidence, mortality, recognized occupational diseases, early detection, and assessment are presented in this article.}, } @article {pmid39060158, year = {2024}, author = {Gislard, A and Gramond, C and Clin, B and Paris, C and Delva, F and Brochard, P and Laurent, F and Benoist, J and Andujar, P and Chouaïd, C and Thaon, I and Boudet, L and Pairon, JC}, title = {[Compensation of occupational diseases during monitoring of the ARDCO cohort].}, journal = {Revue des maladies respiratoires}, volume = {41}, number = {7}, pages = {472-487}, doi = {10.1016/j.rmr.2024.06.010}, pmid = {39060158}, issn = {1776-2588}, mesh = {Humans ; France/epidemiology ; *Occupational Diseases/epidemiology/diagnosis/etiology ; Male ; Middle Aged ; Female ; *Occupational Exposure/adverse effects/statistics & numerical data ; Aged ; *Asbestosis/epidemiology/diagnosis ; Cohort Studies ; *Lung Neoplasms/epidemiology/diagnosis/etiology ; *Workers' Compensation/statistics & numerical data ; *Asbestos/adverse effects ; Adult ; Aged, 80 and over ; Tomography, X-Ray Computed/statistics & numerical data ; Mesothelioma/epidemiology/diagnosis/etiology ; }, abstract = {INTRODUCTION: Questions concerning under-reporting of occupational diseases (OD) linked to asbestos exposure are regularly voiced in France. Monitoring of the French multicenter Asbestos-Related Disease Cohort (ARDCO), which ensures post-occupational medical surveillance of subjects having been exposed to asbestos, provides information on (1) the medico-legal steps taken following screening by computed tomography (CT) for benign thoracic diseases, and (2) recognition of OD as a causal factor in malignant diseases.

METHODS: OD recognition - and possible compensation - was analyzed in July 2021 among 13,289 volunteers in the cohort recruited between 2003 and 2005.

RESULTS: Fifteen percent of the subjects in the cohort were found to have at least one recognized asbestos-related OD (78.2% benign pleural disease, 10.3% asbestosis, 14.2% lung cancer, and 6.0% mesothelioma). Only 58% of pleural plaques reported by the radiologist who performed the CT resulted in their recognition as ODs. On a parallel track, 88.7% of the mesotheliomas identified based on French National health insurance data and 46.9% of lung cancers were recognized as ODs.

CONCLUSIONS: This study confirms the feasibility of a system designed to facilitate recognition, leading to possible compensation, of asbestos-related occupational diseases. The system could be improved by better training of the medical actors involved.}, } @article {pmid39015660, year = {2024}, author = {Neilly, MDJ and Pearson, J and Thu, AW and MacRae, C and Blyth, KG}, title = {Contemporary management of mesothelioma.}, journal = {Breathe (Sheffield, England)}, volume = {20}, number = {2}, pages = {230175}, pmid = {39015660}, issn = {1810-6838}, abstract = {Pleural mesothelioma (PM) is an aggressive asbestos-associated thoracic malignancy with a median survival of 12-18 months. Due to continued asbestos use in many nations, global incidence is rising. Causes due to non-occupational, environmental exposure are also rising in many countries despite utilisation bans. For many years, platinum--pemetrexed chemotherapy was the solitary licensed therapy, but first-line combination immune checkpoint blockade has recently demonstrated improved outcomes, with both regimes tested in predominantly late-stage cohorts. In the second-line setting, single-agent nivolumab has been shown to extend survival and is now available for routine use in some regions, while second-line chemotherapy has no proven role and opportunities for clinical trials should be maximised in relapsed disease. Surgery for "technically resectable" disease has been offered for decades in many expert centres, but the recent results from the phase III MARS2 trial have challenged this approach. There remains no robustly proven standard of care for early-stage PM. The clinical trial landscape for PM is complex and increasingly diverse, making further development of specialist PM multidisciplinary teams an important priority in all countries. The observation of improving outcomes in centres that have adopted this service model emphasises the importance of high-quality diagnostics and equitable access to therapies and trials. Novel therapies targeting a range of aberrations are being evaluated; however, a better understanding of the molecular drivers and their associated vulnerabilities is required to identify and prioritise treatment targets.}, } @article {pmid39015649, year = {2024}, author = {Cravero, JC and Yakubik, T and Wahab, L and Giang, T and Lopez, LM and Newman, MG}, title = {Primary Peritoneal Mesothelioma Affecting the Greater Omentum That Mimicked an Omental Infarction: A Case Report.}, journal = {Case reports in oncology}, volume = {17}, number = {1}, pages = {596-601}, pmid = {39015649}, issn = {1662-6575}, abstract = {INTRODUCTION: Malignant peritoneal mesothelioma (MPM) is a rare cancer that is associated with asbestos exposure. The diagnosis can be difficult given the nonspecific nature of presenting symptoms and the presence of concomitant confounding findings.

CASE PRESENTATION: We report a 71-year-old male who presented with right lower quadrant pain and new-onset ascites. CT imaging of the abdomen/pelvis demonstrated omental stranding concerning for a possible omental infarction. Subsequent imaging showed persistent omental edema but no identifiable soft tissue mass. A biopsy of the omentum showed atypical mesothelial proliferation, but pathology was unable to determine if proliferation was a neoplastic versus reactive process. Surgical oncology performed a diagnostic laparoscopy that showed peritoneal studding of the omentum. Subsequent immunohistochemical staining of the omentum demonstrated preservation of BAP1 expression and loss of MTAP expression, consistent with peritoneal mesothelioma.

CONCLUSION: MPM is a rare and aggressive cancer with an overall poor prognosis. The diagnosis of MPM can be difficult based on the nonspecific clinical presentation, insufficient imaging and laboratory testing, and the presence of concomitant confounding findings, such as with this patient and his admitting diagnosis of omental infarction. This case demonstrates the importance of developing a broad differential while maintaining an awareness of heuristics that can influence clinical decision-making.}, } @article {pmid39014872, year = {2024}, author = {Khan, S and Malik, A and Qureshi, S and Cohen, B and Nadir, A}, title = {Incidental Diagnosis of Malignant Peritoneal Mesothelioma During Liver Transplantation Surgery: A Case Report.}, journal = {The American journal of case reports}, volume = {25}, number = {}, pages = {e943787}, pmid = {39014872}, issn = {1941-5923}, mesh = {Humans ; *Liver Transplantation ; Female ; *Peritoneal Neoplasms/diagnosis ; Middle Aged ; *Incidental Findings ; *Mesothelioma, Malignant/diagnosis ; Mesothelioma/diagnosis ; Lung Neoplasms/diagnosis ; }, abstract = {BACKGROUND Malignant peritoneal mesothelioma (MPM) is a rare, lethal tumor of serous membranes. The most common factor reported in association with MPM is asbestos exposure, while viral infections, genetic predisposition, paraneoplastic syndrome, and altered immunity have been described as well. The diagnosis can be challenging among those with lower tumor burden as well as nonspecific symptoms, and it is not unusual to discover the diagnosis incidentally. CASE REPORT A middle-aged woman with decompensated cirrhosis underwent extensive pre-transplant workup, showing no evidence of malignancy. She had a personal history of asbestos exposure and family history of MPM in the extended family. During transplant surgery, a few peritoneal nodules were noted, leading to termination of the procedure. Pathological analysis confirmed malignant MPM. A multidisciplinary discussion led to following a conservative treatment approach without any intervention, due to higher risk of worsening hepatic decompensation associated with peritonectomy and intraperitoneal chemotherapy. The patient's hepatic decompensation resolved 6 months after the aborted liver transplant operation. Since the diagnosis of MPM, positron emission tomography scans have shown no recurrence of MPM for 3 consecutive years. CONCLUSIONS This is the first case of MPM diagnosed incidentally during a liver transplantation surgery. This case highlights the challenges in the diagnosis and management of MPM in a patient with decompensated liver disease. A multidisciplinary approach and following a consensus decision led to prolonged survival in the described patient.}, } @article {pmid39011477, year = {2024}, author = {Costa, A and Forte, IM and Pentimalli, F and Iannuzzi, CA and Alfano, L and Capone, F and Camerlingo, R and Calabrese, A and von Arx, C and Benot Dominguez, R and Quintiliani, M and De Laurentiis, M and Morrione, A and Giordano, A}, title = {Pharmacological inhibition of CDK4/6 impairs diffuse pleural mesothelioma 3D spheroid growth and reduces viability of cisplatin-resistant cells.}, journal = {Frontiers in oncology}, volume = {14}, number = {}, pages = {1418951}, pmid = {39011477}, issn = {2234-943X}, abstract = {INTRODUCTION: Diffuse pleural mesothelioma (DPM) of the pleura is a highly aggressive and treatment-resistant cancer linked to asbestos exposure. Despite multimodal treatment, the prognosis for DPM patients remains very poor, with an average survival of 2 years from diagnosis. Cisplatin, a platinum-based chemotherapy drug, is commonly used in the treatment of DPM. However, the development of resistance to cisplatin significantly limits its effectiveness, highlighting the urgent need for alternative therapeutic strategies. New selective inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6) have shown promise in various malignancies by inhibiting cell cycle progression and suppressing tumor growth. Recent studies have indicated the potential of abemaciclib for DPM therapy, and a phase II clinical trial has shown preliminary encouraging results.

METHODS: Here, we tested abemaciclib, palbociclib, and ribociclib on a panel of DPM cell lines and non-tumor mesothelial(MET-5A) cells.

RESULTS: Specifically, we focused on abemaciclib, which was the mosteffective cytotoxic agent on all the DPM cell lines tested. Abemaciclib reduced DPM cell viability, clonogenic potential, and ability to grow as three-dimensional (3D) spheroids. In addition, abemaciclib induced prolonged effects, thereby impairing second-generation sphere formation and inducing G0/G1 arrest and apoptosis/ necrosis. Interestingly, single silencing of RB family members did not impair cell response to abemaciclib, suggesting that they likely complement each other in triggering abemaciclib's cytostatic effect. Interestingly, abemaciclib reduced the phosphorylation of AKT, which is hyperactive in DPM and synergized with the pharmacological AKT inhibitor (AKTi VIII). Abemaciclib also synergized with cisplatin and reduced the viability of DPM cells with acquired resistance to cisplatin.

DISCUSSION: Overall, our results suggest that CDK4/6 inhibitors alone or in combination with standard of care should be further explored for DPM therapy.}, } @article {pmid39006698, year = {2024}, author = {Sonobe, H and Omote, R and Habara, T and Washio, K and Yamazoe, N and Matsumoto, S and Nabeshima, K and Toda, H}, title = {A Rare Case of Pleural Epithelioid Mesothelioma With a Prominent Myxoid Stroma Reported With Morphology, Fluorescent In Situ Hybridization, and Ultrastructural Findings.}, journal = {Cureus}, volume = {16}, number = {6}, pages = {e62212}, pmid = {39006698}, issn = {2168-8184}, abstract = {Herein, we report a rare case of pleural epithelioid malignant mesothelioma with a prominent myxoid stroma. To date, detailed morphological or molecular pathological findings have not been reported for this type of tumor. Hence, we aimed to describe the cytological, histological, immuno-cytohistological, electron-microscopic, and molecular pathological findings using fluorescence in situ hybridization (FISH) in such a case. The patient was a male in his mid-sixties with a history of asbestos exposure and had originally visited the hospital with a persistent cough and fever. Chest radiography revealed left pleural effusion, and laboratory examination revealed a high titer for hyaluronic acid in the effusion. Additionally, computed tomography revealed diffuse multinodular or cystic lesions in the left parietal pleura, and pleural effusion cytology revealed large epithelioid cells with mild nuclear atypia, which were considered reactive mesothelial cells. Cytologically, Giemsa staining revealed that these cells harbored variously sized intracytoplasmic vacuoles that were Alcian-blue-positive, suggesting hyaluronan production. Biopsy revealed large epithelioid cells that loosely proliferated against a prominent myxoid background. These cells were immuno-positive for calretinin, Wilms' tumor 1, D2-40, vimentin, and cytokeratin AE1/AE3 but not for carcinoembryonic antigen, Ber-EP4, or desmin. BRCA 1 associated protein 1 immunostaining showed nuclear loss, and FISH showed homozygous deletion of cyclin-dependent kinase inhibitor 2A (p16) on chromosome 9p21. Based on these findings, the lesion was diagnosed as an epithelioid mesothelioma with a prominent myxoid stroma. Electron-microscopy demonstrated a dense microvillus pattern on the surface of the tumor cells, indicating a mesothelial cell origin, and variously sized vacuoles in the cytoplasm, confirming the presence of intracytoplasmic vacuoles demonstrated on cytology. The tumor tissues obtained during surgery harbored prominent myxoid stroma, which proved that the present tumor was consistent with this type of mesothelioma. After informed consent was obtained, the patient and family wished for total resection of the tumor and postoperative chemotherapy, and the patient eventually died eight months after surgery.}, } @article {pmid39003938, year = {2024}, author = {van Zandwijk, N and Frank, AL and Reid, G and Dimitri Røe, O and Amos, CI}, title = {Asbestos-Related lung Cancer: An underappreciated oncological issue.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {194}, number = {}, pages = {107861}, doi = {10.1016/j.lungcan.2024.107861}, pmid = {39003938}, issn = {1872-8332}, mesh = {Humans ; *Lung Neoplasms/etiology/epidemiology ; *Asbestos/adverse effects ; Environmental Exposure/adverse effects ; Incidence ; Air Pollution/adverse effects ; Occupational Exposure/adverse effects ; Particulate Matter/adverse effects ; }, abstract = {Asbestos, a group of class I (WHO) carcinogenic fibers, is the main cause of mesothelioma. Asbestos inhalation also increases the risk to develop other solid tumours with lung cancer as the most prominent example [91]. The incidence of asbestos-related lung cancer (ARLC) is estimated to be to six times larger than the mesothelioma incidence thereby becoming an important health issue [86]. Although the pivotal role of asbestos in inducing lung cancer is well established, the precise causal relationships between exposures to asbestos, tobacco smoke, radon and 'particulate' (PM2.5) air pollution remain obscure and new knowledge is needed to establish appropriate preventive measures and to tailor existing screening practices[22,61,65]. We hypothesize that a part of the increasing numbers of lung cancer diagnoses in never-smokers can be explained by (historic and current) exposures to asbestos as well as combinations of different forms of air pollution (PM2.5, asbestos and silica).}, } @article {pmid38995135, year = {2024}, author = {Mirabelli, D and Terracini, B}, title = {Carcinogenicity of asbestos-free talc and talcum powder: A systematic review of the epidemiological evidence after the 2006 monograph of the International Agency for Research on Cancer.}, journal = {Epidemiologia e prevenzione}, volume = {48}, number = {3}, pages = {220-232}, doi = {10.19191/EP24.3.A688.057}, pmid = {38995135}, issn = {1120-9763}, mesh = {Female ; Humans ; Male ; Carcinogens/toxicity ; Case-Control Studies ; Cosmetics ; Endometrial Neoplasms/epidemiology/chemically induced ; Lung Neoplasms/epidemiology/chemically induced/etiology ; Neoplasms/epidemiology/chemically induced/etiology ; *Occupational Diseases/epidemiology/chemically induced ; *Occupational Exposure/adverse effects ; Ovarian Neoplasms/epidemiology/chemically induced ; *Talc/adverse effects ; }, abstract = {BACKGROUND: in 2006, the International Agency for Research on Cancer (IARC) concluded that the evidence of carcinogenicity for asbestos-free talc was inadequate (group 3), whereas perineal use of talcum powder was classified as possibly carcinogenic (group 2B).

OBJECTIVES: to assess whether later studies provide more solid information on the carcinogenic risk from asbestos-free talc and talcum powder and a better characterization of exposure.

DESIGN: systematic review.

METHODS: cohort studies of talc miners and millers exposed to asbestos-free talc, as well as cohort and case-control studies reporting cancer risk in talc powder consumers published from 2006 onwards were identified through PubMed and reference lists. Pooled analyses were included, but not reviews and meta-analyses. In the case of repeatedly reported studies, the article with the longest follow-up or the largest number of observed cases was selected for data abstraction. Notice was taken of studies which were both reported individually and included in pooled analyses.

RESULTS: publications meeting inclusion criteria were: 2 cohort studies on talc miners and millers, 10 cohort studies on talcum powder users (4 of which estimated ovarian cancer risk), and 14 case-control studies (13 on ovarian and 1 on endometrial cancer) on the risk from talcum powder use. No excess cancer mortality has been reported among asbestos-free talc miners and millers. Case-control studies consistently led to estimates of ovarian cancer excesses associated with the use of perineal talcum powder (odds ratios up to 1.5). Most studies quantifying exposure also provided evidence of a dose-response relationship. Individual cohort studies estimated hazard ratios (HR) just above 1. In an analysis of pooled cohorts for a total of 3,112 cases, the HR for women with patent reproductive tract was 1.13 (95%CI 1.01-1.26) with a correlation between HR and frequency of use (p for trend 0.03). In all cohort studies, the perineal use of talcum powder was measured only once in the early phases of follow-up, thus producing an inaccurate measure of cumulative exposure. Results of epidemiological studies regarding cancer risk in other organs are limited and inconsistent.

CONCLUSIONS: epidemiological studies updated or published after IARC 2006 evaluation indicate that: no increase in cancer risk is apparent among miners and millers of asbestos-free talc; risk for ovarian cancer increases following the perineal use of commercial talcum powder. A correlation between indicators of quantity of use and cancer risk is suggested by a number of studies. The composition of talcum powders considered in such studies is not known.}, } @article {pmid38990952, year = {2024}, author = {Novelli, F and Yoshikawa, Y and Vitto, VAM and Modesti, L and Minaai, M and Pastorino, S and Emi, M and Kim, JH and Kricek, F and Bai, F and Onuchic, JN and Bononi, A and Suarez, JS and Tanji, M and Favaron, C and Zolondick, AA and Xu, R and Takanishi, Y and Wang, Z and Sakamoto, G and Gaudino, G and Grzymski, J and Grosso, F and Schrump, DS and Pass, HI and Atanesyan, L and Smout, J and Savola, S and Sarin, KY and Abolhassani, H and Hammarström, L and Pan-Hammarström, Q and Giorgi, C and Pinton, P and Yang, H and Carbone, M}, title = {Germline BARD1 variants predispose to mesothelioma by impairing DNA repair and calcium signaling.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {29}, pages = {e2405231121}, pmid = {38990952}, issn = {1091-6490}, support = {R01 CA198138/CA/NCI NIH HHS/United States ; S10 OD028515/OD/NIH HHS/United States ; 853057/ERC_/European Research Council/International ; IG-19803//Italian Association for Cancer Research/ ; PRIN2017E5L5P3 t//AROSE, Progetti di Rilevante Interesse Nazionale/ ; C-1792//Welch Foundation (The Welch Foundation)/ ; GR-2013-02356747//Italian Ministry of Health/ ; R01 ES030948/ES/NIEHS NIH HHS/United States ; 5U01CA214195-04//the Early Detection Research Network NCI/ ; 1R01ES030948-01//HHS | NIH | National Institute of Environmental Health Sciences (NIEHS)/ ; IG-23670//Italian Association for Cancer Research/ ; 1R01CA237235-01A1//HHS | NIH | National Cancer Institute (NCI)/ ; 1R01CA198138//US Department of Defence/ ; R01 CA237235/CA/NCI NIH HHS/United States ; PHY-2019745//NSF/ ; U01 CA214195/CA/NCI NIH HHS/United States ; PRIN20177E9EPY//AROSE, Progetti di Rilevante Interesse Nazionale/ ; }, mesh = {Humans ; *DNA Repair/genetics ; *Tumor Suppressor Proteins/genetics/metabolism ; *Germ-Line Mutation ; *Ubiquitin-Protein Ligases/genetics/metabolism ; *Mesothelioma/genetics ; *Genetic Predisposition to Disease ; *Calcium Signaling/genetics ; Female ; Male ; Middle Aged ; Tumor Suppressor Protein p53/genetics/metabolism ; Apoptosis/genetics ; Fibroblasts/metabolism ; Asbestos/toxicity ; Genomic Instability ; }, abstract = {We report that ~1.8% of all mesothelioma patients and 4.9% of those younger than 55, carry rare germline variants of the BRCA1 associated RING domain 1 (BARD1) gene that were predicted to be damaging by computational analyses. We conducted functional assays, essential for accurate interpretation of missense variants, in primary fibroblasts that we established in tissue culture from a patient carrying the heterozygous BARD1[V523A] mutation. We found that these cells had genomic instability, reduced DNA repair, and impaired apoptosis. Investigating the underlying signaling pathways, we found that BARD1 forms a trimeric protein complex with p53 and SERCA2 that regulates calcium signaling and apoptosis. We validated these findings in BARD1-silenced primary human mesothelial cells exposed to asbestos. Our study elucidated mechanisms of BARD1 activity and revealed that heterozygous germline BARD1 mutations favor the development of mesothelioma and increase the susceptibility to asbestos carcinogenesis. These mesotheliomas are significantly less aggressive compared to mesotheliomas in asbestos workers.}, } @article {pmid38970770, year = {2024}, author = {Cedres, S and Calvete, J and Taylor-Stokes, G and Ayerza, NÁ and Larena, DV and Daumont, M}, title = {Treatment patterns and humanistic burden of malignant pleural mesothelioma in Spain.}, journal = {Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico}, volume = {}, number = {}, pages = {}, pmid = {38970770}, issn = {1699-3055}, abstract = {PURPOSE: Malignant pleural mesothelioma (MPM) is an aggressive cancer with long latency and poor prognosis. The real-world treatment patterns and humanistic burden of MPM in an international cohort of patients were recently published. Spanish data are currently lacking and are reported here.

METHODS/PATIENTS: Data were collected from three sources: physician-abstracted demographic, clinical and treatment characteristics of patients with MPM; patient-completed questionnaires on treatment satisfaction, symptoms, caregiver use, and impact of the disease; and caregiver-completed questionnaire reporting their activity and its impact on their daily life.

RESULTS: The 241 patients in Spain were primarily elderly (median age: 67 years), male, retired/unemployed/on long-term sick leave, and diagnosed at stage IV with unresectable disease. Exposure to asbestos was detected (54%, 101/188). First-line treatment (1L) consisted primarily of doublet chemotherapy (86%, 207/241). Of 102 patients who completed 1L at data abstraction, 67 were receiving maintenance therapy, most commonly singlet chemotherapy with pemetrexed. Best supportive care was given to 29 patients, primarily after 1L (86.2%, 25/29). Symptom burden was high and health-related quality of life was poor and declined with progression: mean (SD) EQ-5D score and EQ-5D visual analogue scale score were 0.615 (0.285) and 60.8 (17.1) in 1L and 0.497 (0.370) and 56.1 (19.5) in second line. Overall, 67% of patients (162/241) required daily assistance from their caregiver, who reported an impact on their psychological well-being.

CONCLUSIONS: Patients with MPM in Spain were overall treated according to treatment guidelines at the time. Nevertheless, a considerable burden of disease was reported by patients and caregivers.}, } @article {pmid38968839, year = {2024}, author = {Andersson, EM and Barregard, L and Akerstrom, M and Sallsten, G and Järvholm, B and Nilsson, RI}, title = {Cancer incidence in Swedish oil refinery workers exposed to benzene.}, journal = {International journal of hygiene and environmental health}, volume = {261}, number = {}, pages = {114420}, doi = {10.1016/j.ijheh.2024.114420}, pmid = {38968839}, issn = {1618-131X}, mesh = {Humans ; *Benzene/toxicity ; Sweden/epidemiology ; *Occupational Exposure/adverse effects ; Male ; Incidence ; *Oil and Gas Industry ; Middle Aged ; Adult ; *Leukemia/epidemiology/chemically induced ; Occupational Diseases/epidemiology/chemically induced ; Retrospective Studies ; Neoplasms/epidemiology/chemically induced ; Air Pollutants, Occupational ; }, abstract = {BACKGROUND: Oil refinery workers are exposed to benzene, which is a well-known cause of leukaemia, but results on leukaemia in oil refinery workers have been mixed, and the data on workers' exposure is limited. Oil refinery workers are also exposed to asbestos and several studies have shown increased risk of mesothelioma.

AIM: The objective was to investigate cancer incidence, especially leukaemia, at low to moderate exposure to benzene in an update of a previous study of employees at three Swedish oil refineries.

METHODS: Cancer incidence was followed up in 2264 men (1548 refinery operators) employed at three oil refineries in Sweden for at least one year. Job types and employment times were collected from complete company files. A retrospective assessment of the benzene exposure was performed by occupational hygienists in collaboration with the refineries using historic measurements as well as detailed information on changes in the industrial hygiene and technological developments. Cases of cancer were retrieved by a linkage with the Swedish Cancer Register through 35-47 years of follow-up and standardized incidence ratios (SIR) with 95% confidence intervals (CI) were calculated.

RESULTS: In total, 258 tumors had occurred versus 240 expected (SIR 1.07; 95% CI 0.95-1.21). There were 10 cases of leukaemia, all in refinery operators (SIR 2.4; 95% CI 1.18-4.51). There were three cases of pleural mesothelioma, two of which in refinery operators. The mean estimated cumulative benzene exposure for the cases of leukaemia was 7.9 ppm-years (median 4.9, range 0.1-31.1).

DISCUSSION: The study suggests that low to moderate average cumulative benzene exposure increases the risk of leukaemia. Limitations include the modest number of cases and potential misclassification of exposure.

CONCLUSION: The present study indicated an increased risk of leukaemia in male oil refinery workers with low to moderate exposure to benzene.}, } @article {pmid38955483, year = {2024}, author = {Berge, LAM and Shala, NK and Barone-Adesi, F and Hosgood, HD and Samuelsen, SO and Bråtveit, M and Kirkeleit, J and Silverman, D and Friesen, MC and Babigumira, R and Grimsrud, TK and Veierød, MB and Stenehjem, JS}, title = {Exposure to fibres and risk of pleural mesothelioma in the Norwegian Offshore Petroleum Workers cohort.}, journal = {Occupational and environmental medicine}, volume = {81}, number = {7}, pages = {331-338}, doi = {10.1136/oemed-2024-109424}, pmid = {38955483}, issn = {1470-7926}, mesh = {Humans ; Norway/epidemiology ; *Occupational Exposure/adverse effects ; Male ; *Asbestos/adverse effects ; Middle Aged ; *Mesothelioma/epidemiology/etiology/chemically induced ; *Pleural Neoplasms/epidemiology/etiology/chemically induced ; *Occupational Diseases/epidemiology/chemically induced/etiology ; Adult ; Aged ; *Ceramics/adverse effects ; *Petroleum/adverse effects ; Cohort Studies ; Mesothelioma, Malignant/epidemiology/etiology ; Risk Factors ; Oil and Gas Industry ; Lung Neoplasms/epidemiology/etiology/chemically induced ; Mineral Fibers/adverse effects ; Case-Control Studies ; Proportional Hazards Models ; }, abstract = {OBJECTIVES: Pleural mesothelioma is a rare respiratory cancer, mainly caused by inhalation of asbestos fibres. Other inorganic fibres are also suggested risk factors. We aimed to investigate the association between exposure to asbestos or refractory ceramic fibres (RCFs) and pleural mesothelioma among male Norwegian offshore petroleum workers.

METHODS: Among 25 347 men in the Norwegian Offshore Petroleum Workers (NOPW) cohort (1965-1998), 43 pleural mesothelioma cases were identified through the Cancer Registry of Norway (1999-2022). A case-cohort study was conducted with 2095 randomly drawn non-cases from the cohort. Asbestos and RCF exposures were assessed with expert-made job-exposure matrices (JEMs). Weighted Cox regression was used to estimate HRs and 95% CIs, adjusted for age at baseline and pre-offshore employment with likely asbestos exposure.

RESULTS: An increased risk of pleural mesothelioma was indicated for the highest versus lowest tertile of average intensity of asbestos (HR=1.21, 95% CI: 0.57 to 2.54). Pre-offshore asbestos exposure (vs no such exposure) was associated with increased risk of pleural mesothelioma (HR=2.06, 95% CI: 1.11 to 3.81). For offshore workers with no pre-offshore asbestos exposure, an increased risk of pleural mesothelioma was found for the highest tertile of average intensity of asbestos (HR=4.13, 95% CI: 0.93 to 18), versus the lowest tertile. No associations were found between RCF and pleural mesothelioma.

CONCLUSIONS: Associations between JEM-based offshore asbestos exposure and pleural mesothelioma were confirmed in the NOPW cohort. Pleural mesothelioma risk was also associated with asbestos exposure before work in the offshore petroleum industry.}, } @article {pmid38954660, year = {2024}, author = {Zhao, Z and Li, J and Tan, F and Xue, Q and Gao, S and He, J}, title = {Assessing the global burden of mesothelioma: trends, socioeconomic influences, and asbestos exposure: a retrospective cohort study.}, journal = {International journal of surgery (London, England)}, volume = {}, number = {}, pages = {}, doi = {10.1097/JS9.0000000000001900}, pmid = {38954660}, issn = {1743-9159}, abstract = {INTRODUCTION: Mesothelioma is an uncommon type of cancer which has received little attention. This study aims to evaluate the global disease burden; trends of mesothelioma by age, sex, and geographic locations; and its risk factors on the population level.

METHODS: The Global Cancer Observatory in 2022 and 2019 Global Burden of Disease were accessed for mesothelioma incidence and its risk factors worldwide. Multivariable linear regression analyses was conducted to explore the associations between mesothelioma incidence and key predictors including Human Development Index (HDI), Gross Domestic Product (GDP) per capita, and occupational asbestos exposure, adjusting for age and sex across global regions.

RESULTS: This study identified 30,870 global cases of mesothelioma in 2022, with a higher age-standardized incidence rate (ASR) in males (0.25 per 100,000) compared to females (0.39 per 100,000). Geographical analysis indicated the highest disease burden in Northern Europe, with particular prevalence in more developed regions. The incidence was also significantly associated with higher Human Development Index (HDI), with a beta coefficient of 0.133 overall, and Gross Domestic Product (GDP) per capita, with a beta coefficient of 0.101. These socioeconomic factors exhibited stronger associations in the elderly population, especially with HDI (β=0.512) and GDP (β=0.389), than in adults. Additionally, occupational exposure to asbestos remained a significant risk factor across all groups, except for the younger adult population, with an overall beta of 0.122 for incidence. The temporal trend analysis revealed a general decrease in mesothelioma incidence, particularly in the 15-49 years age group.

CONCLUSIONS: The analysis indicates a higher mesothelioma incidence in males and in developed regions, with marked disparities noted particularly in Northern Europe. Significant correlations with socioeconomic indicators-HDI and GDP-and occupational asbestos exposure were identified, particularly affecting the elderly. Despite a decline in global incidence, especially among younger individuals, persistent cases in females highlight the need for continued public health measures addressing both occupational and environmental exposures.}, } @article {pmid38952736, year = {2024}, author = {De Maria, L and Pentimone, F and Cavone, D and Caputi, A and Sponselli, S and Fragassi, F and Dicataldo, F and Luisi, V and Delvecchio, G and Giannelli, G and Cafaro, F and Sole, S and Ronghi, C and Zagaria, S and Loiacono, G and Sifanno, G and Ferri, GM and Vimercati, L}, title = {Clinical investigation of former workers exposed to asbestos: the health surveillance experience of an Italian University Hospital.}, journal = {Frontiers in public health}, volume = {12}, number = {}, pages = {1411910}, pmid = {38952736}, issn = {2296-2565}, mesh = {Humans ; Italy/epidemiology ; *Occupational Exposure/adverse effects ; Male ; *Asbestos ; *Hospitals, University ; Female ; Middle Aged ; *Asbestosis/epidemiology ; Aged ; Mesothelioma, Malignant ; Adult ; Lung Neoplasms/epidemiology/etiology ; Population Surveillance ; Pleural Neoplasms/epidemiology/etiology ; Mesothelioma/epidemiology/etiology ; }, abstract = {BACKGROUND: The need for health surveillance of former workers exposed to asbestos was provided by law in Italy after the asbestos ban in 1992.

OBJECTIVES: We describe the results of the health surveillance of former workers exposed to asbestos, conducted over 27 years, from 1994 to 2020, at the Operative Unit of Occupational Medicine of the University Hospital of Bari.

MATERIALS AND METHODS: We adopted the health surveillance protocol, which was validated at the national level in 2018.

RESULTS: A total of 1,405 former workers exposed to asbestos were examined. We proceeded with diagnosing pathologies in 339 cases (24% of the cohort subjected to surveillance), with diagnoses of some cases involving multiple pathologies. Specifically, pleural plaques were diagnosed in 49.2% of the 339 cases, asbestosis in 35.9%, malignant pleural mesothelioma (MPM) in 20.3%, mesothelioma of the vaginal tunic of the testis (MTVT) in 9.1%, lung cancer in 5.8%, and laryngeal cancer in 0.8%.

CONCLUSION: Despite the 1992 asbestos ban, asbestos-related diseases remain a serious public health issue. It is important to establish criteria that ensure the health surveillance of formerly exposed workers minimizes costs, reduces the number of invasive examinations, and optimizes achievable results.}, } @article {pmid38951010, year = {2024}, author = {Sherborne, V and Ejegi-Memeh, S and Tod, AM and Taylor, B and Hargreaves, S and Gardiner, C}, title = {Living with mesothelioma: a systematic review of mental health and well-being impacts and interventions for patients and their informal carers.}, journal = {BMJ open}, volume = {14}, number = {6}, pages = {e075071}, pmid = {38951010}, issn = {2044-6055}, mesh = {Humans ; *Mesothelioma/psychology/therapy ; *Caregivers/psychology ; *Mental Health ; Quality of Life ; Anxiety/etiology ; Depression/etiology ; }, abstract = {OBJECTIVES: Mesothelioma is an aggressive cancer predominantly affecting the lung and abdominal linings. It can have a unique impact on mental health and well-being (MHWB) due to its incurability, poor prognosis and asbestos-exposure causation. This review's aims were to identify/synthesise international evidence on mesothelioma's MHWB impacts; explore MHWB interventions used by patients and carers; and identify evidence of their effectiveness.

DESIGN: Systematic review.

DATA SOURCES: Databases, searched March 2022 and March 2024, were MEDLINE; CINAHL; PsycINFO; Cochrane Library; ASSIA.

ELIGIBILITY CRITERIA: We included study designs focusing on psychological impacts of living with mesothelioma and MHWB interventions used by patients and informal carers, published in English since January 2002.

DATA EXTRACTION AND SYNTHESIS: A team of reviewers screened included studies using standardised methods. Quality was assessed using validated tools: Mixed-Methods Appraisal tool for primary research and Joanna Briggs Institute Critical Appraisal Checklist for Systematic Reviews.

RESULTS: Forty-eight studies met the inclusion criteria: 20 qualitative, 16 quantitative, nine reviews, two mixed-methods, one combined systematic review/qualitative study. UK studies predominated. Many MHWB impacts were reported, including traumatic stress, depression, anxiety and guilt. These were influenced by mesothelioma's causation, communication issues and carer-patient relational interactions. Participants used wide-ranging MHWB interventions, including religious/spiritual practice; talking to mental-health professionals; meaning-making. Some strategies were presented as unhelpful, for example, denial. Participants reported lack of access to support.

CONCLUSIONS: Most qualitative studies were rated high quality. The quality of the quantitative studies and reviews varied. The sparse literature regarding MHWB in mesothelioma means more research is needed into impacts on patients and carers, including trauma. To enable access to evidence-based support, research is recommended concerning MHWB interventions' effectiveness in mesothelioma.

PROSPERO REGISTRATION NUMBER: CRD42022302187.}, } @article {pmid38943482, year = {2024}, author = {Girardi, P and Rigoni, S and Ferrante, D and Silvestri, S and Angelini, A and Cuccaro, F and Oddone, E and Vicentini, M and Barone-Adesi, F and Tunesi, S and Migliore, E and Roncaglia, F and Sala, O and Pirastu, R and Chellini, E and Miligi, L and Perticaroli, P and Bressan, V and Merler, E and Azzolina, D and Marinaccio, A and Massari, S and Magnani, C}, title = {Asbestos exposure and asbestosis mortality in Italian cement-asbestos cohorts: Dose-response relationship and the role of competing death causes.}, journal = {American journal of industrial medicine}, volume = {67}, number = {9}, pages = {813-822}, doi = {10.1002/ajim.23629}, pmid = {38943482}, issn = {1097-0274}, support = {//Istituto Superiore di Sanità/ ; //Istituto Nazionale per l'Assicurazione Contro Gli Infortuni sul Lavoro/ ; //The Italian National Institute of Health (ISS)/ ; //The INAIL/ ; }, mesh = {Humans ; *Asbestosis/mortality ; Italy/epidemiology ; *Occupational Exposure/adverse effects/analysis ; Male ; *Asbestos ; Middle Aged ; *Construction Materials/adverse effects ; Female ; *Cause of Death ; Aged ; Cohort Studies ; *Lung Neoplasms/mortality ; Pleural Neoplasms/mortality ; Proportional Hazards Models ; Peritoneal Neoplasms/mortality ; Occupational Diseases/mortality ; Adult ; Dose-Response Relationship, Drug ; }, abstract = {OBJECTIVES: In Italy, asbestos was used intensively until its ban in 1992, which was extended for asbestos cement factories until 1994. The aim of this study was to evaluate the dose-response between asbestos exposure and asbestosis mortality across a pool of Italian occupational cohorts, taking into account the presence of competing risks.

METHODS: Cohorts were followed for vital status and the cause of death was ascertained by a linkage with mortality registers. Cause-specific (CS) Cox-regression models were used to evaluate the dose-exposure relationship between asbestosis mortality and the time-dependent cumulative exposure index (CEI) to asbestos. Fine and Gray regression models were computed to assess the effect of competing risks of death.

RESULTS: The cohort included 12,963 asbestos cement workers. During the follow-up period (1960-2012), of a total of 6961 deaths, we observed 416 deaths attributed to asbestosis, 879 to lung cancer, 400 to primary pleural cancer, 135 to peritoneal cancer, and 1825 to diseases of the circulatory system. The CS model showed a strong association between CEI and asbestosis mortality. Dose-response models estimated an increasing trend in mortality even below a CEI of 25 ff/mL-years. Lung cancer and circulatory diseases were the main competing causes of death.

CONCLUSIONS: Asbestos exposure among Italian asbestos-cement workers has led to a very high number of deaths from asbestosis and asbestos-related diseases. The increasing risk trend associated with excess deaths, even at low exposure levels, suggests that the proposed limit values would not have been adequate to prevent disability and mortality from asbestosis.}, } @article {pmid38920665, year = {2024}, author = {Zhand, S and Liao, J and Castorina, A and Yuen, ML and Ebrahimi Warkiani, M and Cheng, YY}, title = {Small Extracellular Vesicle-Derived Circular RNA hsa_circ_0007386 as a Biomarker for the Diagnosis of Pleural Mesothelioma.}, journal = {Cells}, volume = {13}, number = {12}, pages = {}, pmid = {38920665}, issn = {2073-4409}, support = {2023/24 ideas to action//NSW Dust Diseases board (iCare)/ ; }, mesh = {Humans ; *RNA, Circular/genetics/metabolism ; *Extracellular Vesicles/metabolism/genetics ; *Biomarkers, Tumor/genetics/metabolism ; *Mesothelioma/genetics/diagnosis ; Cell Line, Tumor ; Pleural Neoplasms/genetics/diagnosis ; Gene Expression Regulation, Neoplastic ; Mesothelioma, Malignant/genetics/diagnosis ; }, abstract = {Pleural mesothelioma (PM) is a highly aggressive tumor that is caused by asbestos exposure and lacks effective therapeutic regimens. Current procedures for PM diagnosis are invasive and can take a long time to reach a definitive result. Small extracellular vesicles (sEVs) have been identified as important communicators between tumor cells and their microenvironment via their cargo including circular RNAs (circRNAs). CircRNAs are thermodynamically stable, highly conserved, and have been found to be dysregulated in cancer. This study aimed to identify potential biomarkers for PM diagnosis by investigating the expression of specific circRNA gene pattern (hsa_circ_0007386) in cells and sEVs using digital polymerase chain reaction (dPCR). For this reason, 5 PM, 14 non-PM, and one normal mesothelial cell line were cultured. The sEV was isolated from the cells using the gold standard ultracentrifuge method. The RNA was extracted from both cells and sEVs, cDNA was synthesized, and dPCR was run. Results showed that hsa_circ_0007386 was significantly overexpressed in PM cell lines and sEVs compared to non-PM and normal mesothelial cell lines (p < 0.0001). The upregulation of hsa_circ_0007386 in PM highlights its potential as a diagnostic biomarker. This study underscores the importance and potential of circRNAs and sEVs as cancer diagnostic tools.}, } @article {pmid38902063, year = {2024}, author = {Couchman, E and Ejegi-Memeh, S and Mitchell, S and Gardiner, C}, title = {Rethinking continuity in primary care for people with mesothelioma.}, journal = {The British journal of general practice : the journal of the Royal College of General Practitioners}, volume = {74}, number = {suppl 1}, pages = {}, doi = {10.3399/bjgp24X737373}, pmid = {38902063}, issn = {1478-5242}, mesh = {Humans ; *Continuity of Patient Care ; *Primary Health Care ; *Mesothelioma/therapy ; Male ; Female ; State Medicine ; United Kingdom ; Middle Aged ; Qualitative Research ; Aged ; Lung Neoplasms/therapy ; Attitude of Health Personnel ; }, abstract = {BACKGROUND: Mesothelioma is a terminal disease that is linked to asbestos exposure. Continuity is difficult for GPs, and other healthcare professionals (HCPs), to provide within the current NHS primary care system, but is highly valued by people with mesothelioma.

AIM: To understand the experiences of continuity in primary care among people with mesothelioma, their close persons, and their HCPs; how they achieve this (or not); and how it affects their healthcare service use.

METHOD: Realist case studies of patient journeys through the healthcare system (involving longitudinal interviews with people with mesothelioma, their close persons, and HCPs; and exploration of the organisational context). Data analysis allowed understanding of hidden mechanisms (resources and reasoning), triggered in certain contexts, leading to specific outcomes.

RESULTS: Forty-eight interviews (involving 9 patients, 8 close persons, and 12 HCPs) were undertaken (totalling 30.8 hours/1848 minutes). Context-Mechanism-Outcome configurations related to: challenges unique to mesothelioma; capacity of patients/close persons/HCPs to facilitate continuity; multidisciplinary (MDT) approach differs from the family doctor model; and 'the NHS primary care system is broken'.

CONCLUSION: Patients perceive their continuity needs to be unmet by the inflexible primary care system, which needs to adapt to a society in which people receive increasingly novel treatments and live longer with complex healthcare needs. A societal perspective shift is required to understand that an MDT now shares responsibility for care, rather than an individual family doctor. Policy documents continue to focus on access, and still do not advocate strongly enough for continuity, despite unequivocal evidence demonstrating its worth.}, } @article {pmid38891178, year = {2024}, author = {Santos, C and Sacadura-Leite, E and Ferreira, J and Dixe, MDA and Astoul, P and Sousa-Uva, A}, title = {The Pleural Mesothelioma Cases and Mortality in Portugal in 2014-2020: A Descriptive Study.}, journal = {Healthcare (Basel, Switzerland)}, volume = {12}, number = {11}, pages = {}, pmid = {38891178}, issn = {2227-9032}, abstract = {BACKGROUND: The incidence and mortality of pleural mesothelioma (PM) reflect the production and consumption of asbestos over time. However, despite the current global concern, these data remain to be known.

OBJECTIVE: Our aim was to carry out a descriptive analysis of PM cases and mortality from some Portuguese databases between 2014 and 2020.

METHODS: A retrospective observational study was carried out between 2014 and 2020. Data on the number of PM cases were provided by the Portuguese Cancer Registry, and data on mortality were from the Portuguese Death Certificate Information System.

RESULTS: Between 2014 and 2020, 315 cases of PM were reported, with 222 (70.5%) men. The average age of patients was 72.1, with the highest number of cases in patients aged >70 years (n = 198; 62.9%). The highest number of cases was reported in 2018 (n = 62; 19.7%). Regarding mortality, 169 deaths were reported, with 126 (74.6%) men and mostly in individuals aged >70 years (n = 109; 64.5%). It is estimated that around 520 years of potential life were lost. The highest number of deaths occurred in 2015 (n = 33; 19.5%).

CONCLUSION: It is mandatory to reinforce the need for surveillance programs that allow us to gather real and reliable data and eliminate asbestos-related diseases.}, } @article {pmid38886298, year = {2024}, author = {Lin, RT and Boonhat, H and Lin, YY and Klebe, S and Takahashi, K}, title = {Health Effects of Occupational and Environmental Exposures to Nuclear Power Plants: A Meta-Analysis and Meta-Regression.}, journal = {Current environmental health reports}, volume = {11}, number = {3}, pages = {329-339}, pmid = {38886298}, issn = {2196-5412}, support = {CMU112-MF-76 and CMU111-MF-82//China Medical University, Taiwan/ ; 111-2314-B-039-020-MY2 and 110-2314-B-039-058//National Science and Technology Council, Taiwan/ ; }, mesh = {*Nuclear Power Plants ; Humans ; *Occupational Exposure/adverse effects/analysis ; *Radiation Exposure/adverse effects ; *Environmental Exposure/adverse effects ; Neoplasms, Radiation-Induced/epidemiology/etiology ; }, abstract = {PURPOSE OF REVIEW: Numerous epidemiological studies have shown increased health risks among workers and residents living near nuclear power plants exposed to radiation levels meeting regulatory dose limits. This study aimed to evaluate the association between radiation exposure and disease risks among these populations exposed to radiation levels meeting the current regulatory dose limits.

RECENT FINDINGS: We searched four databases (Cochrane Library, PubMed, ScienceDirect, and Web of Science) for studies published before August 2023, screened eligible studies (inclusion and exclusion criteria based on population, exposure, comparator, and outcome framework), and collected data on exposure indicators and disease risks. We applied random-effects models of meta-analysis to estimate the pooled effects and meta-regression to assess the dose-response relationship (radiation dose rate for workers and distance for residents). We identified 47 studies, 13 with worker and 34 with resident samples, covering 175 nuclear power plants from 17 countries, encompassing samples of 480,623 workers and 7,530,886 residents. Workers had a significantly lower risk for all-cancer and a significantly higher risk for mesothelioma. Residents had significantly higher risks for all-cancer, thyroid cancer, and leukemia. Notably, children under 5 years old showed the highest risk for all-cancer. Our meta-regression showed a significantly positive dose-response relationship between cumulative dose of radiation exposure and risk for circulatory disease among workers. Our findings demonstrated higher risks for mesothelioma for workers and all-cancer, thyroid cancer, and leukemia for residents exposed to low-dose radiation from nuclear power plants. Some included studies did not adjust for cancer risk confounders, which could overestimate the association between radiation exposure and cancer risk and increase the risk of bias.}, } @article {pmid38880927, year = {2024}, author = {Fu, F and Zhang, Y and Shen, H}, title = {[Advances in Targeted Therapy for Malignant Pleural Mesothelioma].}, journal = {Zhongguo fei ai za zhi = Chinese journal of lung cancer}, volume = {27}, number = {5}, pages = {391-398}, pmid = {38880927}, issn = {1999-6187}, mesh = {Humans ; *Mesothelioma, Malignant/drug therapy/therapy ; *Mesothelioma/drug therapy/therapy ; *Lung Neoplasms/drug therapy/therapy/genetics ; *Molecular Targeted Therapy ; Pleural Neoplasms/drug therapy/therapy ; Animals ; Endoplasmic Reticulum Chaperone BiP ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare cancer with high malignancy and aggressiveness on the pleural, caused by the following risk factors including asbestos inhalation, genetic factors, and genetic mutation. The present chemotherapy, antiangiogenic therapy, and immunotherapy methods are ineffective and the survival time of patients is very short. There is an urgent need to find potential therapeutic targets for MPM. At present, it has been found the following types of targets: gene mutation targets such as BRCA associated protein 1 (BAP1) and cyclin-dependent kinase 2A (CDKN2A); epigenetic targets such as lysine (K)-specific demethylase 4A (KDM4A) and lysine-specific demethylase 1 (LSD1), and signal protein targets such as glucose-regulated protein 78 (GRP78) and signal transducer and activator of transcription 3 (STAT3). So far, available clinical trials include phase II clinical trials of histone methyltransferase inhibitor Tazemetostat, poly (ADP-ribose) polymerase (PARP) inhibitor Rucaparib and cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor Abemaciclib, as well as phase I clinical trials of mesothelin-targeting chimeric antigen receptor T-cell immunotherapy (CAR-T) cell injection in the thoracic cavity and TEA domain family member (TEAD) inhibitor VT3989 and IK-930, and the results of these trials have showed certain clinical efficacy. .}, } @article {pmid38858710, year = {2024}, author = {Huh, DA and Choi, YH and Kim, L and Park, K and Lee, J and Hwang, SH and Moon, KW and Kang, MS and Lee, YJ}, title = {Air pollution and survival in patients with malignant mesothelioma and asbestos-related lung cancer: a follow-up study of 1591 patients in South Korea.}, journal = {Environmental health : a global access science source}, volume = {23}, number = {1}, pages = {56}, pmid = {38858710}, issn = {1476-069X}, mesh = {Humans ; Male ; Republic of Korea/epidemiology ; *Lung Neoplasms/mortality ; Female ; Aged ; Middle Aged ; *Mesothelioma, Malignant/mortality ; *Air Pollutants/adverse effects/analysis ; Follow-Up Studies ; *Air Pollution/adverse effects ; Asbestos/adverse effects ; Environmental Exposure/adverse effects ; Particulate Matter/adverse effects/analysis ; Aged, 80 and over ; Adult ; Mesothelioma/mortality/epidemiology ; }, abstract = {BACKGROUND: Despite significant advancements in treatments such as surgery, radiotherapy, and chemotherapy, the survival rate for patients with asbestos-related cancers remains low. Numerous studies have provided evidence suggesting that air pollution induces oxidative stress and inflammation, affecting acute respiratory diseases, lung cancer, and overall mortality. However, because of the high case fatality rate, there is limited knowledge regarding the effects of air pollution exposures on survival following a diagnosis of asbestos-related cancers. This study aimed to determine the effect of air pollution on the survival of patients with malignant mesothelioma and asbestos-related lung cancer.

METHODS: We followed up with 593 patients with malignant mesothelioma and 998 patients with lung cancer identified as asbestos victims between 2009 and 2022. Data on five air pollutants-sulfur dioxide, carbon monoxide, nitrogen dioxide, fine particulate matter with a diameter < 10 μm, and fine particulate matter with a diameter < 2.5 μm-were obtained from nationwide atmospheric monitoring stations. Cox proportional hazard models were used to estimate the association of cumulative air pollutant exposure with patient mortality, while adjusting for potential confounders. Quantile-based g-computation was used to assess the combined effect of the air pollutant mixture on mortality.

RESULTS: The 1-, 3-, and 5-year survival rates for both cancer types decreased with increasing exposure to all air pollutants. The estimated hazard ratios rose significantly with a 1-standard deviation increase in each pollutant exposure level. A quartile increase in the pollutant mixture was associated with a 1.99-fold increase in the risk of malignant mesothelioma-related mortality (95% confidence interval: 1.62, 2.44). For lung cancer, a quartile increase in the pollutant mixture triggered a 1.87-fold increase in the mortality risk (95% confidence interval: 1.53, 2.30).

CONCLUSION: These findings support the hypothesis that air pollution exposure after an asbestos-related cancer diagnosis can negatively affect patient survival.}, } @article {pmid38857841, year = {2024}, author = {Chornkrathok, S and Carbone, M and Yang, H and Rouf, M and Dodson, RF and Dera, P}, title = {Mineralogical investigation of asbestos contamination of soil near old vermiculite processing plant in Honolulu, Hawai'i.}, journal = {Environmental pollution (Barking, Essex : 1987)}, volume = {356}, number = {}, pages = {124350}, doi = {10.1016/j.envpol.2024.124350}, pmid = {38857841}, issn = {1873-6424}, mesh = {*Aluminum Silicates ; Hawaii ; *Soil Pollutants/analysis ; *Asbestos/analysis ; *Environmental Monitoring ; *Mining ; *Soil/chemistry ; Asbestos, Amphibole ; }, abstract = {From 1954 to 1983, a vermiculite processing facility operated near the Honolulu airport and processed raw material from the Libby, Montana mine, which is now well known for the high asbestos content of its clay deposits. The factory was closed in 1983 due to health hazard concerns, and remediation was performed in 2001 as part of the Libby mine superfund project. However, because of close proximity of the closed-down facility to residential areas of metropolitan Honolulu, some concerns remain regarding the possible environmental persistence of the harmful contaminant. To assess the dispersion of asbestos-contaminated vermiculite and explore the impact of trade winds on its distribution, air samples, and soil samples were collected from multiple locations near the former vermiculite plant. Polarized light microscopy was employed to identify elongated minerals, including potential asbestos. Quantitative mineralogical analysis utilizing X-ray powder diffraction and Rietveld refinement revealed an average content of approximately 7% vermiculite and 4% tremolite at the site. The asbestiform nature of tremolite was confirmed through X-ray micro-diffraction. Detailed analysis of airborne samples using transmission electron microscopy revealed no detectable levels of asbestos fibers in the vicinity of the former processing facilities, but the possibility of asbestos fibers becoming airborne due to mechanical disturbance during dry weather cannot be ruled out.}, } @article {pmid38854177, year = {2024}, author = {Potesta, MA and Guld, E and Laman, J}, title = {Dual Malignancies Discovered: A Rare Case of Malignant Peritoneal Epithelioid Mesothelioma and Lung Adenocarcinoma.}, journal = {Cureus}, volume = {16}, number = {5}, pages = {e59962}, pmid = {38854177}, issn = {2168-8184}, abstract = {Clinicians diagnosing malignant peritoneal epithelioid mesothelioma (MPM or MPeM) have historically had challenges due to the low incidence of the disease, as well as the often vague symptomatology that patients present with. Newer advances in technology, specifically in immunocytochemistry, have provided a clearer path to diagnosis. Additionally, malignant mesotheliomas must be differentiated from carcinomas. This is done via histology, immunocytochemistry, as well as a careful incorporation of the patient's clinical history. In this case, we present an asymptomatic 73-year-old non-smoker female with no past medical history of asbestos exposure. She was diagnosed with MPM following a routine abdominal hernia repair. Subsequent workup revealed a lung infiltrate that was successfully biopsied and resected, evidently found to be adenocarcinoma. A careful review of the resulting pathology, as well as the interpretation of immunocytochemistry, supported the notion that the patient had two independent malignant processes occurring at once. This case underscores the rarity of two similar, yet distinct cancers, as well as epidemiology, symptomatology, histology, immunocytochemistry, and prognosis.}, } @article {pmid38806867, year = {2024}, author = {Chen, Z and Cai, Y and Ou, T and Zhou, H and Li, H and Wang, Z and Cai, K}, title = {Global burden of mesothelioma attributable to occupational asbestos exposure in 204 countries and territories: 1990-2019.}, journal = {Journal of cancer research and clinical oncology}, volume = {150}, number = {5}, pages = {282}, pmid = {38806867}, issn = {1432-1335}, support = {2022A028//the Dean Research Funding of Nanfang Hospital, Southern Medical University, China/ ; }, mesh = {Humans ; *Occupational Exposure/adverse effects ; *Asbestos/adverse effects ; Male ; Female ; *Global Burden of Disease ; Middle Aged ; Aged ; Adult ; Mesothelioma/epidemiology/mortality/etiology ; Mesothelioma, Malignant/epidemiology/mortality/etiology ; Disability-Adjusted Life Years ; Lung Neoplasms/epidemiology/etiology/mortality ; Aged, 80 and over ; Global Health/statistics & numerical data ; Occupational Diseases/epidemiology/mortality/etiology ; }, abstract = {Malignant mesothelioma, a rare and aggressive cancer primarily caused by occupational asbestos exposure, has a poor prognosis. This study leverages the Global Burden of Disease (GBD) 2019 dataset to analyze the burden of mesothelioma linked to occupational asbestos exposure from 1990 to 2019. The analysis includes the number of mesothelioma deaths and disability-adjusted life years (DALYs) attributable to occupational asbestos exposure, focusing on trends in age-standardized mortality rate (ASMR) and age-standardized disability-adjusted life-year rate (ASDR) by year, age, sex, country, region, and Socio-demographic Index (SDI). In 2019, 91.7% of mesothelioma deaths and 85.2% of DALYs were attributable to occupational asbestos exposure, resulting in 26,820 (95% UI 24,312-28,622) deaths and 569,429 (95% UI 509,956-617,484) DALYs. Despite a decline in ASMR and ASDR from 1990 to 2019, the absolute number of deaths and DALYs almost doubled. The United States reported the highest number of mesothelioma deaths, while China had the highest number of DALYs. Age-specific mortality rates and DALYs decreased in the 25-74 age group but increased in the 75+ age group. In conclusion, occupational asbestos exposure remains the primary cause of mesothelioma worldwide, with an increasing number of deaths and DALYs. The highest incidence rates are observed in high-income areas, and rates are rising in low-income areas. It is crucial to raise awareness about the hazards of asbestos to reduce the global burden of mesothelioma linked to occupational exposure.}, } @article {pmid38806807, year = {2024}, author = {Albano, GD and Rodolico, V and Di Franco, S and Re, GL and Midiri, M and Malta, G and Cannizzaro, E and Argo, A and Zerbo, S}, title = {Asbestos exposure determined 357 days after death through autopsy: a report of a multidisciplinary approach.}, journal = {Forensic science, medicine, and pathology}, volume = {}, number = {}, pages = {}, pmid = {38806807}, issn = {1556-2891}, abstract = {Asbestosis is an interstitial lung disease caused by the inhalation of asbestos fibers and poses a significant risk to individuals working in construction, shipping, mining, and related industries. In a forensic context, postmortem investigations are crucial for accurate diagnosis, for which the gold standard is the histopathological examination. This case report describes the autopsy and related investigations conducted on an 84-year-old man, nearly one year (357 days) after his death. After a post-mortem CT scan, an autoptic investigation was performed, followed by histopathological, immunohistochemical, and scanning electron microscopy examinations. The integration of the evidence from these examinations with previously available personal and clinical information conclusively confirmed the diagnosis of asbestosis. We demonstrated the efficacy and reliability of our diagnostic protocol in detecting asbestosis and asbestos fibers and excluding mesothelioma even in decomposed tissues. According to our findings autopsy remains the diagnostic gold standard in cases of suspected asbestosis within a forensic context, even 1 year after death, therefore it is always highly recommended, even in cases where the body has decomposed.}, } @article {pmid38806763, year = {2024}, author = {Yaşar, S and Yılmaz, F and Utkan, G and Algın, E and Bayram, D and Tamam, S and Öksüzoğlu, ÖBÇ and İlhan, A and Erdat, EC and Ünal, AE and Yalçın, Ş}, title = {Analysis of Treatment Strategies and Outcomes in Malignant Peritoneal Mesothelioma: Insights From a Multi-Center Study.}, journal = {Annals of surgical oncology}, volume = {31}, number = {9}, pages = {6228-6236}, pmid = {38806763}, issn = {1534-4681}, mesh = {Humans ; *Peritoneal Neoplasms/therapy/secondary/mortality ; Female ; Male ; Middle Aged ; Retrospective Studies ; *Cytoreduction Surgical Procedures ; *Mesothelioma, Malignant/therapy/pathology ; Survival Rate ; Prognosis ; Aged ; Follow-Up Studies ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; *Hyperthermic Intraperitoneal Chemotherapy ; Adult ; Combined Modality Therapy ; Lung Neoplasms/therapy/pathology/mortality ; }, abstract = {BACKGROUND: This study aimed to evaluate the demographic," clinicopathologic, and prognostic characteristics of malignant peritoneal mesothelioma (MPeM), as well as the treatment options for the rare and heterogeneous MPeM population.

METHODS: A retrospective multi-center observational cohort study was conducted to evaluate patients with MPeM. Due to the heterogeneity of the study population, the study divided them into two main groups in terms of treatments, follow-up periods, and prognostic features. The first group comprised the patients who underwent cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), and the second group included the patients with metastatic disease for whom curative intent surgery was not possible. The patients' diagnostic procedures and treatments were identified from medical records. Patients older than 18 years old were included in the study regardless of asbestos exposure. Well-differentiated papillary and multicystic mesothelioma histologic types were not included in the study.

RESULTS: The study evaluated 118 patients from five centers. Survival times, prognosis, and treatment responses were analyzed in both groups. The study showed that CRS-HIPEC was associated with longer overall survival (OS) and progression-free survival (PFS). Perioperative therapy was evaluated in subgroup analyses of this population and shown to provide survival benefits. The patients treated with chemotherapy (metastatic and medically inoperable patients and those for whom complete cytoreduction was not achievable) had a poorer prognosis than the surgery group. The study showed that life expectancy decreased significantly for the patients not suitable to undergo surgery for any reason.

CONCLUSIONS: According to data from experienced centers, CRS-HIPEC is a treatment option recognized as effective, cost-effective, and safe, with better OS and PFS , as well as low morbidity and mortality rates similar to those in the literature. In addition, the platinum-pemetrexed combination continues to be an effective and acceptable treatment option for metastatic patients, those who are medically inoperable, and those for whom complete or near-complete cytoreduction is not achievable.}, } @article {pmid38803090, year = {2024}, author = {Altshuler, PC and Newman, AL and Garibay, JA}, title = {Rapid Progression of Malignant Peritoneal Mesothelioma Mimicking a Postoperative Complication in a Young Woman: A Case Report.}, journal = {The American journal of case reports}, volume = {25}, number = {}, pages = {e942948}, pmid = {38803090}, issn = {1941-5923}, mesh = {Humans ; Female ; Adult ; *Peritoneal Neoplasms/diagnosis ; *Postoperative Complications/diagnosis ; *Ovarian Neoplasms/diagnosis/pathology ; *Mesothelioma, Malignant/diagnosis ; Fatal Outcome ; Diagnosis, Differential ; Disease Progression ; Teratoma/diagnosis/surgery ; Salpingo-oophorectomy ; Mesothelioma/diagnosis ; }, abstract = {BACKGROUND Malignant peritoneal mesothelioma is a rare disease with a poor prognosis that often presents with vague symptoms and inconclusive laboratory test results. Causes include industrial pollutants, primarily asbestos, and certain genetic mutations, such as BAP1. Due to the nonspecific symptoms, it is often incidentally diagnosed during or after other surgical procedures. CASE REPORT A 35-year-old healthy woman underwent an uncomplicated laparoscopic left salpingo-oophorectomy for a symptomatic large ovarian mature cystic teratoma. She subsequently presented with late-onset postoperative fever, leukocytosis, and multiple intra-abdominal masses. Following an exploratory laparotomy, extensive infectious disease evaluation, and multiple biopsies requiring interdisciplinary collaboration, malignant peritoneal mesothelioma was diagnosed by positive histologic staining of an omental biopsy for D2-40 and CK5/6. This first specimen was positive for BAP1, with the second, a liver biopsy, testing negative for BAP1. The tumor cell testing was also notable for mutations in NF2, MLL2, and ARID1A, and the hereditary cancer genetic testing was overall unremarkable. Her disease progressed rapidly, and she died 6 months after her initial procedure. CONCLUSIONS This case of rapidly developing malignant peritoneal mesothelioma following surgical management of an ovarian mature teratoma highlights the complexity in diagnosing a rare disease that presents with nonspecific symptoms in an otherwise young and healthy woman. The rapid disease course was likely accelerated by expansive intraperitoneal spread and multiple somatic oncogenic mutations in BAP1, NF2, MLL2, and ARID1A. Gynecologists should keep a broad differential for postoperative complications, as occult malignancies can present with symptoms that mimic postoperative complications.}, } @article {pmid38798778, year = {2024}, author = {Singh, R and Frank, AL}, title = {Analysis of mesothelioma cases and National Cancer Registry data to assess asbestos exposure in India.}, journal = {Public health action}, volume = {14}, number = {1}, pages = {30-33}, pmid = {38798778}, issn = {2220-8372}, abstract = {SETTING: Asbestos exposure can cause mesothelioma, a form of cancer which should be recorded by cancer registries. However, such registries currently cover only a small fraction (16%) of the population in India. Because India still uses asbestos, it is important to understand its health impact, especially the number of mesothelioma cases.

OBJECTIVE: To assess the number of mesothelioma cases in India and compare these to the number reported to the National Cancer Registry.

DESIGN: We used the Right to Information Act 2005 to gather data for 83 hospitals across India from 2012 to 2022-2023.

RESULTS: From a total of 83 hospitals, there were 2,213 cases of mesothelioma from 2012 onwards. During the 2012-2016 period, the number of reported cases in the Cancer Registry was 54, whereas 1,126 cases were reported by these hospitals for this period. Only 21 (25%) of the hospitals assessed in this study were part of the population-based national cancer registry programme. Overall, cases of mesothelioma occur far more frequently than are reported in cancer registries.

CONCLUSION: National record-keeping is inadequate and the system needs to be expanded and improved across all of India. This will provide more effective reporting and help to highlight the risk of exposure to asbestos.}, } @article {pmid38791896, year = {2024}, author = {Hintermair, S and Iser, S and Varga, A and Biesinger, M and Bohanes, T and Celik, A and Sayan, M and Kankoç, A and Akyurek, N and Öğüt, B and Stubenberger, E and Ghanim, B}, title = {Ki67 Tumor Expression Predicts Treatment Benefit Achieved by Macroscopic Radical Lung-Preserving Surgery in Pleural Mesothelioma-A Retrospective Multicenter Analysis.}, journal = {Cancers}, volume = {16}, number = {10}, pages = {}, pmid = {38791896}, issn = {2072-6694}, abstract = {Pleural mesothelioma (PM), linked to asbestos-induced inflammation, carries a poor prognosis. Therapy ranges from therapy limitation to aggressive multimodality treatment. Given the uncertainty about treatment benefits for patients, this study aimed to assess the role of Ki67 as a prognostic and predictive parameter in PM. Ki67 was measured in the specimens of 70 PM patients (17 female, 53 male) from two centers and correlated to overall survival (OS) and therapy outcome. The median OS was 16.1 months. The level of Ki67 expression was divided into low (≤15%) and high (>15%). A low value of Ki67 expression was associated with a longer OS (Ki67 ≤ 15%: 31.2 (95% CI 6.5-55.8) months vs. Ki67 > 15%: 11.1 (95% CI 7.7-14.6) months, p = 0.012). The 5-year survival represents 22% in the low Ki67 expression group, in contrast to 5% in the high Ki67 expression group. We found a significant interaction term of Ki67 with multimodality treatment (p = 0.031) translating to an OS of 48.1 months in the low expression Ki67 group compared to 24.3 months in the high Ki67 expression group when receiving surgery within multimodality therapy. Therefore, Ki67 stands out as a validated prognostic and, most importantly, novel predictive biomarker for treatment benefits, particularly regarding surgery within multimodality therapy.}, } @article {pmid38789301, year = {2024}, author = {Hassan, A and Prabhakaran, S and Pulford, E and Hocking, AJ and Godbolt, D and Ziad, F and Pandita, A and Wessels, A and Hussey, M and Russell, PA and Klebe, S}, title = {The significance of BAP1 and MTAP/CDKN2A expression in well-differentiated papillary mesothelial tumour: a series of 21 cases and a review of the literature.}, journal = {Pathology}, volume = {56}, number = {5}, pages = {662-670}, doi = {10.1016/j.pathol.2024.02.016}, pmid = {38789301}, issn = {1465-3931}, mesh = {Humans ; *Ubiquitin Thiolesterase/metabolism ; *Tumor Suppressor Proteins/metabolism ; Male ; Female ; Middle Aged ; Aged ; Adult ; *Cyclin-Dependent Kinase Inhibitor p16/metabolism ; *Mesothelioma/pathology/metabolism/diagnosis ; *Biomarkers, Tumor/metabolism/analysis ; Purine-Nucleoside Phosphorylase/metabolism ; Young Adult ; Mesothelioma, Malignant/pathology/diagnosis/metabolism ; Neoplasms, Mesothelial/pathology/metabolism/diagnosis ; Lung Neoplasms/pathology/metabolism/diagnosis ; Pleural Neoplasms/pathology/metabolism/diagnosis ; Immunohistochemistry ; }, abstract = {The nomenclature and diagnostic criteria of well-differentiated papillary mesothelial tumour (WDPMT) have been changed in the 2021 World Health Organization (WHO) classification of thoracic tumours, and a new entity, mesothelioma in situ (MIS), introduced. Histologically these two entities may be similar. However, MIS is regarded as a precursor to invasive mesothelioma and requires demonstration of loss of BAP1 and/or MTAP/CDKN2A for diagnosis, whereas performance of these ancillary tests is desirable but not essential for a diagnosis of WDPMT, in which the significance of BAP1 and/or MTAP/CDKN2A loss is not well understood or well defined. Against this backdrop, we undertook an investigation of 21 cases of WDPMT, identified from our case files and diagnosed according to 2021 WHO criteria, to explore the relationship between histology and BAP1 and MTAP/CDKN2A expression with clinical features including asbestos exposure, focality of tumours and clinical outcome. There were 18 women and three men, with ages ranging from 23-77 years (median 62 years), in which six had a history of asbestos exposure, two had no exposure, and in 13 exposure history was unavailable. Of 20 peritoneal tumours and one pleural tumour, 13 were detected incidentally at the time of surgery for unrelated conditions and eight peritoneal tumours were multifocal at the time of diagnosis. BAP1 immunohistochemistry (IHC) was performed in all 21 tumours, with nine tumours showing BAP1 expression loss. MTAP/CDKN2A testing was performed in 14 tumours, comprising MTAP IHC in 12 and CDKN2A fluorescence in situ hybridisation (FISH) in two, with three tumours showing MTAP/CDKN2A expression loss. Two tumours with MTAP/CDKN2A loss also showed BAP1 expression loss. Four patients progressed to invasive mesothelioma, including one male with a pleural tumour and asbestos exposure, and three females with multifocal peritoneal tumours, two with asbestos exposure and one without exposure. BAP1 expression loss was seen in all tumours from the four patients who progressed to invasive mesothelioma, whilst two of these tumours showed retained MTAP IHC and two were not tested. There was one patient with a tumour with MTAP loss and retained BAP1 who died from unrelated causes 5 months after diagnosis. Eight patients received WDPMT-specific treatment in addition to the initial excision. Survival for all patients ranged from 4-218 months, with one patient dying of mesothelioma at 49 months. Based on our results in this series of 21 patients with WDPMT diagnosed according to 2021 WHO criteria, we propose that WDPMT with BAP1 expression loss may best be regarded as papillary MIS and that a history of asbestos exposure and the presence of multifocal tumours in patients diagnosed with WDPMT should prompt ancillary testing with BAP1 IHC. Further we propose that BAP1 IHC should be essential in the diagnosis of WDPMT, with the diagnosis restricted to those tumours which show retained BAP1 expression. However more studies in larger cohorts of patients are needed to explore the relationship between BAP1 expression and MTAP loss in WDPMT, which will help to define this entity and separate it more clearly from MIS and invasive mesothelioma.}, } @article {pmid38784478, year = {2024}, author = {Testa, JR and Kadariya, Y and Friedberg, JS}, title = {Targeting inflammatory factors for chemoprevention and cancer interception to tackle malignant mesothelioma.}, journal = {Oncoscience}, volume = {11}, number = {}, pages = {53-57}, pmid = {38784478}, issn = {2331-4737}, abstract = {Mesothelioma is an incurable cancer of the mesothelial lining often caused by exposure to asbestos. Asbestos-induced inflammation is a significant contributing factor in the development of mesothelioma, and genetic factors also play a role in the susceptibility to this rapidly progressive and treatment-resistant malignancy. Consequently, novel approaches are urgently needed to treat mesothelioma and prevent or reduce the overall incidence of this fatal disease. In this research perspective, we review the current state of chemoprevention and cancer interception progress in asbestos-induced mesothelioma. We discuss the different preclinical mouse models used for these investigations and the inflammatory factors that may be potential targets for mesothelioma prevention. Preliminary studies with naturally occurring phytochemicals and synthetic agents are reviewed. Results of previous clinical chemoprevention trials in populations exposed to asbestos and considerations regarding future trials are also presented.}, } @article {pmid38781764, year = {2024}, author = {Broggi, G and Massimino, M and Failla, M and Filetti, V and Rapisarda, V and Ledda, C and Lombardo, C and Loreto, C and Vigneri, P and Caltabiano, R}, title = {Concordance between CDKN2A homozygous deletion and MTAP immunohistochemical loss in fluoroedenite-induced pleural mesothelioma: An immunohistochemical and molecular study on a single-institution series.}, journal = {Pathology, research and practice}, volume = {259}, number = {}, pages = {155350}, doi = {10.1016/j.prp.2024.155350}, pmid = {38781764}, issn = {1618-0631}, mesh = {Aged ; Female ; Humans ; Male ; Middle Aged ; Asbestos, Amphibole ; Biomarkers, Tumor/genetics/analysis/metabolism ; *Cyclin-Dependent Kinase Inhibitor p16/genetics/metabolism ; Gene Deletion ; Homozygote ; *Immunohistochemistry ; *Mesothelioma/genetics/pathology/chemically induced/metabolism ; Mesothelioma, Malignant/pathology/genetics ; *Pleural Neoplasms/genetics/pathology/chemically induced/metabolism ; Purine-Nucleoside Phosphorylase/genetics ; }, abstract = {Fluoroedenite-induced pleural mesothelioma (FE-induced-PM) is a rare and small subset of PM that shares with its asbestos-induced counterpart the same aggressive biological behavior and poor prognosis, but that differs from it from a pathogenetic point of view as it is associated with exposure to fluoroedenite, a carcinogenic agent that shows similarities with tremolite amphibolic asbestos fibers. Although it has been demonstrated that asbestos-induced PMs frequently harbor CDKN2A homozygous deletion and that the immunohistochemical loss of MTAP may represent a cheap and reliable surrogate marker for this molecular alteration, little is known about the molecular landscape and the reliability of MTAP immunohistochemistry in this peculiar subset of PM. The study herein presented investigated the prevalence of CDKN2A homozygous deletion and its concordance with MTAP immunohistochemical status on a cohort of 10 cases of FE-induced-PM from patients with environmental exposure to FE fibers, who were residents in the small town of Biancavilla (Sicily, Italy) or nearby areas. CDKN2A homozygous deletions were found in 3 out of 10 cases (30%) and all these cases showed concomitant cytoplasmic loss of MTAP with a concordance rate of 100%. Despite the relatively low number of cases included in our series, MTAP immunohistochemistry seemed to represent a reliable immunohistochemical surrogate marker of CDKNA homozygous deletion even in this subset of PMs.}, } @article {pmid38763755, year = {2024}, author = {Takata, A and Yamauchi, H and Yamashita, K and Aminaka, M and Hitomi, T and Toya, T and Kohyama, N}, title = {Mesothelioma carcinogenesis of chrysotile and forsterite compared and validated by intraperitoneal injection in rat.}, journal = {Industrial health}, volume = {}, number = {}, pages = {}, doi = {10.2486/indhealth.2024-0025}, pmid = {38763755}, issn = {1880-8026}, abstract = {Asbestos, especially chrysotile, continues to be exposed to humans globally. Hence, it should be disposed properly to prevent asbestos-related diseases, including mesothelioma and lung cancer. This study aimed to verify whether forsterite, a heating product of chrysotile, can cause carcinogenicity, particularly mesothelioma. Forsterite (FO-1000) and enstatite (EN-1500) produced by heating chrysotile at 1000°C and 1500°C, respectively, were subjected. We injected 10 mg of chrysotile, FO-1000, or EN-1500 in rats intraperitoneally and observed the development of peritoneal mesothelioma until 24 months. The incidence of peritoneal mesothelioma in the chrysotile group was 91.2%, whereas in the FO-1000 and EN-1500 groups, peritoneal mesothelioma did not develop. Urinary 8-hydroxy-2'-deoxyguanosine and serum N-ERC/mesothelin concentrations significantly increased in the chrysotile group that developed peritoneal mesothelioma, while they only temporarily changed in the FO-1000 or EN-1500 groups during early treatment. Furthermore, there was a significant homozygous deletion of the CDKN2A/p16 gene in the chrysotile group compared to the control group, in contrast to no significant difference in the FO-1000 and EN-1500 groups. Therefore, this study provides clear evidence that forsterite is a nonmesothelioma carcinogen and suggests that forsterite and enstatite are sufficient substances for chrysotile detoxification.}, } @article {pmid38737188, year = {2024}, author = {Hong Lee, AH and Macalister, SJ and Yap, KK}, title = {Pleural small cell lung cancer masquerading as malignant mesothelioma: A case report.}, journal = {Radiology case reports}, volume = {19}, number = {8}, pages = {2969-2972}, pmid = {38737188}, issn = {1930-0433}, abstract = {Nodular soft tissue pleural thickening on imaging is highly suggestive of malignancy, of which pleural malignant mesothelioma and metastatic disease are differentials. We present the case of a 71-year-old male who presented with acute worsening of shortness of breath associated with a recurrent left pleural effusion post-pleurocentesis. He was an ex-smoker with previous asbestos exposure. Computed tomography performed demonstrated left-sided pleural thickening in the hemithorax and hemidiaphragm with complex pleural effusion. [18]F-2-deoxy-d-glucose whole body PET scan revealed extensive uptake throughout the left hemithorax in multiple pleural masses. The imaging findings and clinical case were typical of malignant mesothelioma. However, histopathology results revealed small cell lung cancer. We need to be cognisant of this atypical presentation of a common disease entity. Even when all clinical and imaging findings point towards a certain diagnosis, histopathological assessment cannot be ignored.}, } @article {pmid38736489, year = {2024}, author = {Lapidot, M and Mazzola, E and Bueno, R}, title = {Prolonged survival and novel prognostic factors in women with pleural mesothelioma treated with extended pleurectomy decortication.}, journal = {Translational lung cancer research}, volume = {13}, number = {4}, pages = {811-820}, pmid = {38736489}, issn = {2218-6751}, abstract = {BACKGROUND: Pleural mesothelioma (PM) is an uncommon and extremely aggressive malignancy associated with past exposure to asbestos. The low representation of women among PM patients is likely due to differences in occupational asbestos exposure. Due to the controversial role of female sex as a prognostic factor in PM, the study aims to evaluate the survival of females treated with lung-sparing surgery. We present a cohort of 114 consecutive female patients with PM who underwent intended extended pleurectomy decortication (ePD) over 11 years in a high-volume single institution.

METHODS: All women from 2007-2017 who underwent intended ePD were enrolled in the study. Data on clinical, operative, and outcome were collected. Kaplan-Meier estimators and log-rank tests were employed to assess the overall survival, and Cox regression models were utilized to analyze prognostic factors.

RESULTS: During the study period, 454 patients underwent thoracotomy with intended ePD in a single institution. There were 114 females (25%), and macroscopic complete resection (MCR) was achieved in 97 (85.1%). The median age was 65 years, histology was epithelioid in 81 (71.0%), biphasic in 31 (27.2%), and sarcomatoid in 2 (1.8%). The 30- and 90-day mortality were 3.5% and 6.1%, respectively. Median survival in females was 38 months, and 5-year survival was 28.2%. The median survival and 5-year survival rate for patients with epithelioid histology and MCR were 44.4 months and 36.4%, respectively. In a univariate analysis, several factors were found to be associated with patient overall survival including MCR [hazard ratio (HR): 0.3, P<0.001], early T status (HR: 1.6, P=0.03), adjuvant therapy (HR: 0.5, P=0.006), intraoperative heated chemotherapy (IOHC) (HR: 0.8, P=0.03), age (HR: 1.02, P=0.03) and epithelioid histology (HR: 0.5, P=0.009).

CONCLUSIONS: For women with epithelioid PM undergoing intended ePD within a multimodal setting, prolonged survival is anticipated.}, } @article {pmid38734073, year = {2024}, author = {Bille, A and Ripley, RT and Giroux, DJ and Gill, RR and Kindler, HL and Nowak, AK and Opitz, I and Pass, HI and Wolf, A and Rice, D and Rusch, VW and , }, title = {The International Association for the Study of Lung Cancer Mesothelioma Staging Project: Proposals for the "N" Descriptors in the Forthcoming Ninth Edition of the TNM Classification for Pleural Mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {19}, number = {9}, pages = {1326-1338}, pmid = {38734073}, issn = {1556-1380}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Neoplasm Staging/standards ; *Pleural Neoplasms/pathology/classification ; *Lung Neoplasms/pathology/classification/surgery/mortality ; *Mesothelioma/pathology/classification/mortality/surgery ; Male ; Female ; Mesothelioma, Malignant/pathology/classification/mortality ; Aged ; Middle Aged ; }, abstract = {INTRODUCTION: The International Association for the Study of Lung Cancer developed an international database to inform potential revisions in the ninth edition of the TNM classification of diffuse pleural mesothelioma (PM). This study analyzed the clinical and pathologic N categories to determine whether revisions were indicated relative to the eighth edition staging system.

METHODS: Of 7338 PM cases diagnosed from 2013 to 2022 and 3598 met all inclusion criteria for planned analyses. Data on 2836 patients without metastases were included in this study. Overall survival (OS) was measured from date of diagnosis. Patients were included regardless of whether they received neoadjuvant treatment. For the pathologic N analysis, patients who underwent resection (extrapleural pneumonectomy or pleurectomy/decortication) were included. N subgroups were analyzed and OS assessed by the Kaplan-Meier method.

RESULTS: The existing eighth edition N categories were performed adequately in the ninth edition data set. A median OS advantage was noted for clinical and pathologic N0 versus N1 patients: 23.2 versus 18.5 and 33.8 versus 25.0 months, respectively. Patients with resected pN0 had a 3-year OS of 48%. No difference in OS was noted for single- versus multiple-station nodal metastases. The number of nodal stations sampled at the time of resection was not associated with a difference in OS.

CONCLUSIONS: Data regarding clinical and pathologic N categories corroborate those used in the eighth edition. No changes in the N categories are recommended in the ninth edition of PM staging system.}, } @article {pmid38729555, year = {2024}, author = {Gugnoni, M and Lorenzini, E and Torricelli, F and Donati, B and Manicardi, V and Vitale, E and Muccioli, S and Piana, S and Lococo, F and Zamponi, R and Gandellini, P and Ciarrocchi, A}, title = {Linc00941 fuels ribogenesis and protein synthesis by supporting robust cMYC translation in malignant pleural mesothelioma.}, journal = {Cancer letters}, volume = {592}, number = {}, pages = {216950}, doi = {10.1016/j.canlet.2024.216950}, pmid = {38729555}, issn = {1872-7980}, mesh = {Humans ; *Mesothelioma, Malignant/genetics/pathology/metabolism ; *RNA, Long Noncoding/genetics/metabolism ; *Protein Biosynthesis ; *Eukaryotic Initiation Factor-4G/genetics/metabolism ; *Mesothelioma/genetics/pathology/metabolism ; Cell Line, Tumor ; *Proto-Oncogene Proteins c-myc/genetics/metabolism ; *Lung Neoplasms/genetics/pathology/metabolism ; *Gene Expression Regulation, Neoplastic ; Pleural Neoplasms/genetics/pathology/metabolism ; Ribosomes/metabolism/genetics ; Retrospective Studies ; Prognosis ; Cell Proliferation ; }, abstract = {Malignant pleural mesothelioma is a rare and lethal cancer caused by exposure to asbestos. The highly inflammatory environment caused by fibers accumulation forces cells to undergo profound adaptation to gain survival advantages. Prioritizing the synthesis of essential transcripts is an efficient mechanism coordinated by multiple molecules, including long non-coding RNAs. Enhancing the knowledge about these mechanisms is an essential weapon in combating mesothelioma. Linc00941 correlates to bad prognosis in various cancers, but it is reported to partake in distinct and apparently irreconcilable processes. In this work, we report that linc00941 supports the survival and aggressiveness of mesothelioma cells by influencing protein synthesis and ribosome biogenesis. Linc00941 binds to the translation initiation factor eIF4G, promoting the selective protein synthesis of cMYC, which, in turn, enhances the expression of key genes involved in translation. We analyzed a retrospective cohort of 97 mesothelioma patients' samples from our institution, revealing that linc00941 expression strongly correlates with reduced survival probability. This discovery clarifies linc00941's role in mesothelioma and proposes a unified mechanism of action for this lncRNA involving the selective translation of essential oncogenes, reconciling the discrepancies about its function.}, } @article {pmid38724155, year = {2024}, author = {Bluhm, M and Atmeh, B and Boehm, S and Rüschoff, JH and Bode, P and Dommann-Scherrer, C}, title = {Pleural Effusion Caused by an Unusual Mass in the Right Hemithorax.}, journal = {Chest}, volume = {165}, number = {5}, pages = {e151-e155}, doi = {10.1016/j.chest.2024.01.025}, pmid = {38724155}, issn = {1931-3543}, mesh = {Humans ; Female ; Aged, 80 and over ; *Tomography, X-Ray Computed ; Pleural Effusion/etiology/diagnosis ; Diagnosis, Differential ; Pleural Neoplasms/complications/diagnosis ; }, abstract = {An 80-year-old woman presented with complaints of weakness and dizziness. She had a medical history of subacute cerebral ischemia, vertigo, hypertension, and thalassemia minor. The patient was born and raised in Turkey and has lived in Switzerland for 50 years. Her sister died of a mesothelioma caused by asbestos exposure at the age of 60 years but had lived in Turkey until her death. The patient had neither a history of TB nor B symptoms. She has never smoked.}, } @article {pmid38722058, year = {2024}, author = {Stirpe, E and Bardaro, F and Köhl, J}, title = {Gluteal muscle metastases from malignant pleural mesothelioma: a case report.}, journal = {Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace}, volume = {}, number = {}, pages = {}, doi = {10.4081/monaldi.2024.2629}, pmid = {38722058}, issn = {2532-5264}, abstract = {Malignant pleural mesothelioma (MPM) is a rare malignancy arising from the mesothelial or subthelial layer of the pleura, and it has increased in recent decades, mainly associated with asbestos exposure. Sarcomatoid mesothelioma is the second-most common subtype of MPM. It is usually difficult to differentiate MPM from benign mesothelial pleural proliferations or other cancers. Because of its nonspecific symptoms, MPM is often diagnosed at a late stage with distal metastases. However, it is extremely rare to see a metastatic lesion within subcutaneous tissue and muscles, which is most likely caused by hematogenous spread. We present a case of sarcomatoid mesothelioma with a metastatic lesion of the right gluteal muscles.}, } @article {pmid38711818, year = {2024}, author = {Syed Ahmad, SD and Kirk, F and Wijesinghe, W and He, C and Stroebel, A}, title = {A peculiar presentation of tamponade: pericardial mesothelioma.}, journal = {Journal of surgical case reports}, volume = {2024}, number = {5}, pages = {rjae279}, pmid = {38711818}, issn = {2042-8812}, abstract = {Pericardial mesothelioma (PM) is rare with only 200 cases recorded, and a post-mortem prevalence of <0.0022%. It is the third most common cardiac/pericardial tumour, behind angiosarcoma and rhabdomyosarcoma. PM incidence increases with age, typically incidentally diagnosed between 50 and 70 years, with a 3:1 male predominance. Occasional PM can cause chest pain, dyspnoea, cough and even dysphagia. PMs are often misdiagnosed with only 25% of cases being antemortem diagnoses. Unlike pleural mesothelioma, the link between asbestos exposure and malignancy is less convincing, with only 20% of cases having known exposure. 6 There are three histological types: epithelioid, fibrous (spindle cell), and biphasic (mixed). The average life-expectancy post diagnosis is 3-10 months. Due to the heterogeneity of the presentation and rarity there is no standardized management algorithm, and the diagnostic imaging or laboratory investigations are scarcely described. We are presenting one of the cases diagnosed in our unit here in the Gold Coast.}, } @article {pmid38702329, year = {2024}, author = {Chin, WL and Zemek, RM and Tilsed, CM and Forrest, ARR and Fear, VS and Forbes, C and Boon, L and Bosco, A and Guo, BB and Millward, MJ and Nowak, AK and Lake, RA and Lesterhuis, WJ and Lassmann, T}, title = {Time-course RNAseq data of murine AB1 mesothelioma and Renca renal cancer following immune checkpoint therapy.}, journal = {Scientific data}, volume = {11}, number = {1}, pages = {448}, pmid = {38702329}, issn = {2052-4463}, support = {APP1154524//Department of Health | National Health and Medical Research Council (NHMRC)/ ; }, mesh = {Animals ; Mice ; *Carcinoma, Renal Cell/drug therapy/genetics ; *Immune Checkpoint Inhibitors/therapeutic use ; *Kidney Neoplasms/drug therapy/genetics ; *Mesothelioma/drug therapy/genetics ; RNA-Seq ; Sequence Analysis, RNA ; Single-Cell Analysis ; *Tumor Microenvironment ; }, abstract = {Time-critical transcriptional events in the immune microenvironment are important for response to immune checkpoint blockade (ICB), yet these events are difficult to characterise and remain incompletely understood. Here, we present whole tumor RNA sequencing data in the context of treatment with ICB in murine models of AB1 mesothelioma and Renca renal cell cancer. We sequenced 144 bulk RNAseq samples from these two cancer types across 4 time points prior and after treatment with ICB. We also performed single-cell sequencing on 12 samples of AB1 and Renca tumors an hour before ICB administration. Our samples were equally distributed between responders and non-responders to treatment. Additionally, we sequenced AB1-HA mesothelioma tumors treated with two sample dissociation protocols to assess the impact of these protocols on the quality transcriptional information in our samples. These datasets provide time-course information to transcriptionally characterize the ICB response and provide detailed information at the single-cell level of the early tumor microenvironment prior to ICB therapy.}, } @article {pmid38699968, year = {2024}, author = {Lombardo, C and Maugeri, G and D'Amico, AG and Broggi, G and Caltabiano, R and Filetti, V and Matera, S and D'Agata, V and Loreto, C}, title = {Pleural mesothelioma from fluoro-edenite exposure: PACAP and PAC1 receptor. A preliminary report.}, journal = {European journal of histochemistry : EJH}, volume = {68}, number = {2}, pages = {}, pmid = {38699968}, issn = {2038-8306}, mesh = {Humans ; *Pituitary Adenylate Cyclase-Activating Polypeptide/metabolism ; Male ; *Mesothelioma/metabolism/pathology/chemically induced ; Middle Aged ; *Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I/metabolism ; Female ; *Pleural Neoplasms/metabolism/pathology/chemically induced ; Aged ; Asbestos, Amphibole/toxicity ; Mesothelioma, Malignant/metabolism/pathology ; Lung Neoplasms/metabolism/pathology/chemically induced ; Immunohistochemistry ; Biomarkers, Tumor/metabolism ; }, abstract = {Pleural mesothelioma is a devastating malignancy primarily associated with asbestos exposure. However, emerging evidence suggests that exposure to fluoro-edenite fibers, a naturally occurring mineral fiber, can also lead to the development of pleural mesothelioma. In this study, based on the hypothesis that pituitary adenylate cyclase-activating polypeptide (PACAP) and PACAP-preferring receptor (PAC1R) expressions could be dysregulated in pleural mesothelioma samples and that they could potentially act as diagnostic or prognostic biomarkers, we aimed to investigate the immunohistochemical expression of PACAP and PAC1R in pleural biopsies from patients with pleural mesothelioma exposed to fluoro-edenite fibers. A total of 12 patients were included in this study, and their biopsies were processed for immunohistochemical analysis to evaluate the expression of PACAP and its receptor. The study revealed a correlation between the overexpression of PACAP and PAC1R and shorter overall survival in patients with malignant mesothelioma. These findings suggest that PACAP and PAC1R expression levels could serve as potential prognostic biomarkers for malignant mesothelioma. Furthermore, the immunohistochemical analysis of PACAP and PAC1R may provide valuable information for clinicians to guide therapeutic decisions and identify patients with poorer prognosis.}, } @article {pmid38694815, year = {2024}, author = {Fisher, SA and Patrick, K and Hoang, T and Marcq, E and Behrouzfar, K and Young, S and Miller, TJ and Robinson, BWS and Bueno, R and Nowak, AK and Lesterhuis, WJ and Morahan, G and Lake, RA}, title = {The MexTAg collaborative cross: host genetics affects asbestos related disease latency, but has little influence once tumours develop.}, journal = {Frontiers in toxicology}, volume = {6}, number = {}, pages = {1373003}, pmid = {38694815}, issn = {2673-3080}, abstract = {Objectives: This study combines two innovative mouse models in a major gene discovery project to assess the influence of host genetics on asbestos related disease (ARD). Conventional genetics studies provided evidence that some susceptibility to mesothelioma is genetic. However, the identification of host modifier genes, the roles they may play, and whether they contribute to disease susceptibility remain unknown. Here we report a study designed to rapidly identify genes associated with mesothelioma susceptibility by combining the Collaborative Cross (CC) resource with the well-characterised MexTAg mesothelioma mouse model. Methods: The CC is a powerful mouse resource that harnesses over 90% of common genetic variation in the mouse species, allowing rapid identification of genes mediating complex traits. MexTAg mice rapidly, uniformly, and predictably develop mesothelioma, but only after asbestos exposure. To assess the influence of host genetics on ARD, we crossed 72 genetically distinct CC mouse strains with MexTAg mice and exposed the resulting CC-MexTAg (CCMT) progeny to asbestos and monitored them for traits including overall survival, the time to ARD onset (latency), the time between ARD onset and euthanasia (disease progression) and ascites volume. We identified phenotype-specific modifier genes associated with these traits and we validated the role of human orthologues in asbestos-induced carcinogenesis using human mesothelioma datasets. Results: We generated 72 genetically distinct CCMT strains and exposed their progeny (2,562 in total) to asbestos. Reflecting the genetic diversity of the CC, there was considerable variation in overall survival and disease latency. Surprisingly, however, there was no variation in disease progression, demonstrating that host genetic factors do have a significant influence during disease latency but have a limited role once disease is established. Quantitative trait loci (QTL) affecting ARD survival/latency were identified on chromosomes 6, 12 and X. Of the 97-protein coding candidate modifier genes that spanned these QTL, eight genes (CPED1, ORS1, NDUFA1, HS1BP3, IL13RA1, LSM8, TES and TSPAN12) were found to significantly affect outcome in both CCMT and human mesothelioma datasets. Conclusion: Host genetic factors affect susceptibility to development of asbestos associated disease. However, following mesothelioma establishment, genetic variation in molecular or immunological mechanisms did not affect disease progression. Identification of multiple candidate modifier genes and their human homologues with known associations in other advanced stage or metastatic cancers highlights the complexity of ARD and may provide a pathway to identify novel therapeutic targets.}, } @article {pmid38692809, year = {2024}, author = {Li, H and Husain, AN and Moffat, D and Klebe, S}, title = {Nonmesothelial Spindle Cell Tumors of Pleura and Pericardium.}, journal = {Surgical pathology clinics}, volume = {17}, number = {2}, pages = {257-270}, doi = {10.1016/j.path.2024.01.001}, pmid = {38692809}, issn = {1875-9157}, mesh = {Humans ; *Pericardium/pathology ; *Pleural Neoplasms/pathology/diagnosis ; Diagnosis, Differential ; Heart Neoplasms/pathology/diagnosis ; Mesothelioma/pathology/diagnosis ; Sarcoma/pathology/diagnosis ; Biomarkers, Tumor/analysis ; Pleura/pathology ; }, abstract = {Spindle cell lesions of the pleura and pericardium are rare. Distinction from sarcomatoid mesothelioma, which has a range of morphologic patterns, can be difficult, but accurate diagnosis matters. This article provides practical guidance for the diagnosis of pleural spindle cell neoplasms, focusing on primary lesions.}, } @article {pmid38692064, year = {2024}, author = {Nuvoli, B and Sacconi, A and Bottillo, G and Sciarra, F and Libener, R and Maconi, A and Carosi, M and Piperno, G and Mastropasqua, E and Papale, M and Camera, E and Galati, R}, title = {DHEA-S, Androstenedione, 17-β-estradiol signature as novel biomarkers for early prediction of risk of malignant pleural mesothelioma linked to asbestos-exposure: A preliminary investigation.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {175}, number = {}, pages = {116662}, doi = {10.1016/j.biopha.2024.116662}, pmid = {38692064}, issn = {1950-6007}, mesh = {Humans ; *Estradiol/blood ; Male ; *Biomarkers, Tumor/blood ; *Androstenedione/blood ; *Asbestos/toxicity/adverse effects ; Female ; Middle Aged ; *Occupational Exposure/adverse effects ; Aged ; *Mesothelioma, Malignant/blood/diagnosis ; *Lung Neoplasms/blood/diagnosis ; Mesothelioma/blood/diagnosis/chemically induced ; Pleural Neoplasms/blood/diagnosis/chemically induced ; Dehydroepiandrosterone/blood ; Case-Control Studies ; Early Detection of Cancer/methods ; }, abstract = {17-β-estradiol, involved in mesothelioma pathogenesis, and its precursors were explored as potential biomarkers for the early diagnosis of mesothelioma. Using enzyme-linked immunosorbent assay(ELISA) for 17-β-estradiol and ultra-high performance liquid chromatography/tandem mass spectrometry(UHPLC-MS/MS) for 19 17-β-estradiol precursors, a comprehensive analysis of 20steroid hormones was conducted in the serum of mesothelioma patients(n=67), asbestos-exposed healthy subjects(n=39), and non-asbestos-exposed healthy subjects(n=35). Bioinformatics analysis explored three potential serum biomarkers: 17-β-estradiol, DHEA-S, and androstenedione. The results revealed significant differences in 17-β-estradiol levels between mesothelioma patients and both non-asbestos-exposed and asbestos-exposed healthy subjects. No significant variations in serum 17-β-estradiol levels were observed among mesothelioma patients at different stages, suggesting its potential as an early diagnostic marker. 17-β-estradiol levels were similar in mesothelioma patients with environmental and occupational asbestos exposure, while males with occupational asbestos exposure exhibited significantly higher levels of 17-β-estradiol compared to females. Significant reduction in androstenedione and an increase in DHEA-S were observed in asbestos-exposed individuals compared to non-asbestos-exposed individuals. The analysis of DHEA-S-androstenedione-17-β-estradiol signature score showed an increase in asbestos-exposed individuals and mesothelioma patients compared to non-asbestos-exposed individuals, and this score effectively distinguished between the groups. The Cancer Genome Atlas data was utilized to analyze the expression of 5-α-reductase1 and hydroxysteroid-17β-dehydrogenase2 genes. The findings indicated that mesothelioma patients with elevated gene values for 5-α-reductase1 and hydroxysteroid-17β-dehydrogenase2 have a worse or better prognosis on overall survival, respectively. In conclusion, this study suggests 17-β-estradiol, DHEA-S, and androstenedione as biomarkers for mesothelioma risk and early diagnosis of mesothelioma in asbestos-exposed individuals, aiding timely intervention and improved care.}, } @article {pmid38671450, year = {2024}, author = {Gogou, E and Hatzoglou, C and Siachpazidou, D and Zarogiannis, SG and Gourgoulianis, KI}, title = {Asbestos ban policies and mesothelioma mortality in Greece.}, journal = {BMC public health}, volume = {24}, number = {1}, pages = {1177}, pmid = {38671450}, issn = {1471-2458}, mesh = {Humans ; Greece/epidemiology ; Male ; Female ; *Asbestos ; *Mesothelioma/mortality ; Middle Aged ; Aged ; Adult ; Mesothelioma, Malignant/mortality ; Aged, 80 and over ; Environmental Exposure/adverse effects ; Lung Neoplasms/mortality ; }, abstract = {BACKGROUND: Malignant mesothelioma is a rare form of cancer that mostly affects the pleura and has a strong link to asbestos exposure. Greece banned the use of asbestos in 2005, however, the public was already aware of this substance in the 1980s. This research aims to present an overview of Greece's mesothelioma age-standardized mortality rates (ASMR) from 1983 to 2019 by age, gender, and geographic region and to determine whether the actions to ban asbestos impacted these rates.

METHODS: Data were retrieved by the Hellenic Statistical Authority (HSA) from death certificates that mentioned mesothelioma as the cause of death from 1983 to 2019 with details on the residence, gender, and age. Statistical analysis was performed using PRISM 6.0 software, a two-way ANOVA test, Trend analysis was conducted using Joinpoint Regression Program 5.0 software. The linear and non-linear model was used to calculate the age-standardized rates of annual percentage change (APC) and its 95% confidential interval (95% CI).

RESULTS: From 1983 to 2019, 850 total mesothelioma deaths were recorded, the majority of whom were males (634). A rate of 74.6% accounts for males and 25.4% for females, and the ratio of Males: Females was 3:1. Males' ASMR and the whole population's ASMR reached their highest levels in 2011 (0.93/100000person-years and 0.53/100000person-years, respectively). To look for potential changes between the first two decades of the 21st century, we compared the mean ASMR of each geographic region in Greece between two different 10-year subperiods (2000-2009 and 2010-2019). Except for Epirus, all regions of Greece had elevated regional ASMRs, particularly in those with the highest asbestos deposits. Notably, the ASMR in Epirus decreased from 0.54/100000person-years (2000-2009) to 0.31/100000person-years (2010-2019). After 2011, the ASMR for men and the general population stabilized. This stability is important since mesothelioma in men is associated with occupational asbestos exposure. The intriguing discovery of a lower ASMR in Epirus emphasizes the need to raise awareness of the condition and implement effective public health measures.

CONCLUSIONS: In Greece, the annual ASMR for males and the whole population reached its highest level in 2011, which is positive and encouraging and may be a sign that the rate will stabilize during the following years. Moreover, this study showed that the actions made in the 1980s regarding public awareness and surveillance directly impacted the decrease in Epirus rates. Future research, continual awareness, information, and recording are needed to monitor the mesothelioma epidemic. The possible benefit of a mesothelioma registry and the epidemiological surveillance of asbestos-related diseases, particularly mesothelioma mortality, need to be addressed.

TRIAL REGISTRATION: Not applicable.}, } @article {pmid38662022, year = {2024}, author = {Feder, IS and Fruth, E and Tannapfel, A}, title = {[Asbestos: detection and characterization in tissue].}, journal = {Pathologie (Heidelberg, Germany)}, volume = {45}, number = {5}, pages = {333-338}, pmid = {38662022}, issn = {2731-7196}, mesh = {Humans ; *Asbestos/adverse effects/analysis ; *Asbestosis/pathology/diagnosis ; *Lung/pathology/drug effects ; Mesothelioma/diagnosis/chemically induced/pathology/etiology ; Occupational Exposure/adverse effects/analysis ; Lung Neoplasms/diagnosis/pathology ; Microscopy/methods ; }, abstract = {BACKGROUND: When asbestos fibers are inhaled, asbestos bodies can form in the lungs with the involvement of macrophages. It can take decades from the last exposure to the onset of an asbestos-related disease.

OBJECTIVES: The aim of this review is to present methods to detect asbestos bodies in lung tissue, the development of diagnostic criteria and to discuss pros and cons of different methods.

MATERIALS AND METHODS: Observations and evaluations from the German Mesothelioma Register, along with relevant literature review and expert recommendations in guidelines are presented.

RESULTS: Assessing asbestos-related diseases requires recognition of the person's occupational history, the asbestos fiber burden in the lungs, and determining fiber types. Various methods have been developed and validated, including light microscopy techniques such as bright-field microscopy, phase-contrast microscopy, polarization microscopy, and differential interference microscopy, as well as electron microscopy techniques like field-emission-scanning electron microscopy (e.g., FE-SEM) and transmission electron microscopy (TEM).

CONCLUSION: The use of asbestos has been heavily restricted worldwide, even completely banned in Europe. Thus, patients' exposure to asbestos is decreasing. However, asbestos exposure during renovations, demolitions, or through unconscious handling of asbestos-containing materials remains a concern.}, } @article {pmid38642958, year = {2024}, author = {Gómez Herrero, H and Álvarez Galván, B}, title = {Analysis of invasive diagnostic techniques for pathological confirmation of pleural mesothelioma.}, journal = {Radiologia}, volume = {66 Suppl 1}, number = {}, pages = {S3-S9}, doi = {10.1016/j.rxeng.2023.03.005}, pmid = {38642958}, issn = {2173-5107}, mesh = {Male ; Humans ; Female ; Aged ; *Mesothelioma/diagnostic imaging/etiology ; *Pleural Neoplasms/diagnostic imaging/etiology ; *Asbestos/adverse effects ; *Pleural Effusion/chemically induced/complications/pathology ; Diagnostic Imaging ; }, abstract = {BACKGROUND AND OBJECTIVES: Mesothelioma is an infrequent neoplasm with a poor prognosis that is related to exposure to asbestos and whose peak incidence in Europe is estimated from 2020. Its diagnosis is complex; imaging techniques and the performance of invasive pleural techniques being essential for pathological confirmation. The different diagnostic yields of these invasive techniques are collected in the medical literature. The present work consisted of reviewing how the definitive diagnosis of mesothelioma cases in our centre was reached to check if there was concordance with the data in the bibliography.

MATERIALS AND METHODS: Retrospective review of patients with a diagnosis of pleural mesothelioma in the period 2019-2021, analysing demographic data and exposure to asbestos, the semiology of the radiological findings and the invasive techniques performed to reach the diagnosis.

RESULTS: Twenty-six mesothelioma cases were reviewed. 22 men and 4 women. Median age 74 years. 9 patients had a history of asbestos exposure. Moderate-severe pleural effusion was the most frequent radiological finding (23/26). The sensitivity of the invasive techniques was as follows: Cytology 13%, biopsy without image guidance 11%, image-guided biopsy 93%, surgical biopsy 67%.

CONCLUSIONS: In our review, pleural biopsy performed with image guidance was the test that had the highest diagnostic yield, so it should be considered as the initial invasive test for the study of mesothelioma.}, } @article {pmid38640636, year = {2024}, author = {Ejegi-Memeh, S and Sherborne, V and Mayland, C and Tod, A and Taylor, BH}, title = {Mental health and wellbeing in mesothelioma: A qualitative study exploring what helps the wellbeing of those living with this illness and their informal carers.}, journal = {European journal of oncology nursing : the official journal of European Oncology Nursing Society}, volume = {70}, number = {}, pages = {102572}, doi = {10.1016/j.ejon.2024.102572}, pmid = {38640636}, issn = {1532-2122}, mesh = {Humans ; Male ; Female ; Middle Aged ; *Qualitative Research ; *Caregivers/psychology ; Aged ; *Mesothelioma/psychology ; *Mental Health ; United Kingdom ; Quality of Life ; Adult ; Social Support ; Adaptation, Psychological ; Aged, 80 and over ; Interviews as Topic ; }, abstract = {PURPOSE: Mesothelioma is an incurable, asbestos related cancer with a poor prognosis. Little is known about how patients and carers living with the condition manage their mental health and wellbeing needs. This paper reports findings on interventions being used by patients and informal carers living with mesothelioma and those which they find most helpful.

METHODS: In-depth interviews with patients (n = 10) and (informal) carers (n = 11) living with mesothelioma in the UK. We analysed our data inductively using a reflexive thematic analysis approach.

RESULTS: Participants described the importance of both smaller and larger actions and strategies which helped with their mental health. This included spending more time with family and friends and going on holidays. Professionals who participants said supported their mental health journey included not only specialist nurses and mental health professionals but also legal and Asbestos Support Group professionals. The latter demonstrates the unique needs and support required for this population. Exposure to asbestos as the cause of mesothelioma, has led to a social justice aspect of the experience of living with this cancer. Participants reported the importance of collective action to their mental health and wellbeing. The data indicate that patients and carers may have distinct mental health and wellbeing requirements and need to manage these in different ways at different times.

CONCLUSIONS: Findings have implications for nurses and other key professionals working in healthcare, community and legal settings supporting this client group, and for those living with mesothelioma who want to understand ways to enhance their own wellbeing.}, } @article {pmid38634609, year = {2024}, author = {Liu, RA and Wang, BY and Chen, X and Pu, YQ and Zi, JJ and Mei, W and Zhang, YP and Qiu, L and Xiong, W}, title = {Association Study of Pleural Mesothelioma and Oncogenic Simian Virus 40 in the Crocidolite-Contaminated Area of Dayao County, Yunnan Province, Southwest China.}, journal = {Genetic testing and molecular biomarkers}, volume = {28}, number = {5}, pages = {189-198}, doi = {10.1089/gtmb.2023.0532}, pmid = {38634609}, issn = {1945-0257}, mesh = {Humans ; *Simian virus 40/genetics ; China/epidemiology ; Male ; Female ; Middle Aged ; Aged ; *Pleural Neoplasms/epidemiology/virology/genetics ; *Asbestos, Crocidolite ; Mesothelioma/virology/epidemiology/genetics ; Polyomavirus Infections/epidemiology ; Tumor Virus Infections/epidemiology ; Cell Line, Tumor ; Mesothelioma, Malignant/genetics ; Lung Neoplasms/virology/genetics/epidemiology ; Adult ; }, abstract = {Background: In Dayao County, Chuxiong Yi Autonomous Prefecture, Yunnan Province, Southwest China, 5% of the surface is scattered with blue asbestos, which has a high incidence of pleural mesothelioma (PMe). Simian virus 40 (SV40) is a small circular double-stranded DNA polyomavirus that can cause malignant transformation of normal cells of various human and animal tissue types and promote tumor growth. In this study, we investigate whether oncogenic SV40 is associated with the occurrence of PMe in the crocidolite-contaminated area of Dayao County, Yunnan Province, Southwest China. Methods: Tumor tissues from 51 patients with PMe (40 of whom had a history of asbestos exposure) and pleural tissues from 12 non-PMe patients (including diseases such as pulmonary maculopathy and pulmonary tuberculosis) were collected. Three pairs of low-contamination risk primers (SVINT, SVfor2, and SVTA1) were used to detect the gene fragment of SV40 large T antigen (T-Ag) by polymerase chain reaction (PCR). The presence of SV40 T-Ag in PMe tumor tissues and PMe cell lines was detected by Western blotting and immunohistochemical staining with SV40-related antibodies (PAb 101 and PAb 416). Results: PCR, Western blotting, and immunohistochemical staining results showed that the Met5A cell line was positive for SV40 and contained the SV40 T-Ag gene and protein. In contrast, the various PMe cell lines NCI-H28, NCI-H2052, and NCI-H2452 were negative for SV40. PCR was negative for all three sets of low-contamination risk primers in 12 non-PMe tissues and 51 PMe tissues. SV40 T-Ag was not detected in 12 non-PMe tissues or 51 PMe tissues by immunohistochemical staining. Conclusion: Our data suggest that the occurrence of PMe in the crocidolite-contaminated area of Yunnan Province may not be related to SV40 infection and that crocidolite exposure may be the main cause of PMe. The Clinical Trial Registration number: 2020-YXLL20.}, } @article {pmid38630790, year = {2024}, author = {Yang, SR and Jayakumaran, G and Benhamida, J and Febres-Aldana, CA and Fanaroff, R and Chang, J and Gedvilaite, E and Villafania, LB and Sauter, JL and Offin, M and Zauderer, MG and Ladanyi, M}, title = {Diffuse Pleural Mesotheliomas with Genomic Near-Haploidization: A Newly Recognized Subset with Distinct Clinical, Histologic, and Molecular Features.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {30}, number = {13}, pages = {2780-2789}, pmid = {38630790}, issn = {1557-3265}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; P30-CA008748//National Cancer Institute (NCI)/ ; }, mesh = {Humans ; Male ; Female ; Middle Aged ; Aged ; *Pleural Neoplasms/genetics/pathology/mortality ; Mutation ; Loss of Heterozygosity ; Mesothelioma/genetics/pathology ; Adult ; DNA Copy Number Variations ; Genomics/methods ; Biomarkers, Tumor/genetics ; Prognosis ; Aged, 80 and over ; Mesothelioma, Malignant/genetics/pathology ; Lung Neoplasms/genetics/pathology/mortality ; }, abstract = {PURPOSE: Diffuse pleural mesotheliomas (DPM) with genomic near-haploidization (GNH) represent a novel subtype first recognized by The Cancer Genome Atlas project; however, its clinicopathologic and molecular features remain poorly defined.

EXPERIMENTAL DESIGN: We analyzed clinical genomic profiling data from 290 patients with DPM using the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) assay. Allele-specific copy number analysis was performed using the Fraction and Allele-Specific Copy Number Estimates from Tumor Sequencing (FACETS) algorithm.

RESULTS: A total of 210 patients were evaluable for loss of heterozygosity (LOH) analysis using FACETS from MSK-IMPACT tumor:normal sequencing data. In this cohort, GNH, defined as LOH across >80% of the genome, was detected in 10 cases (4.8%). Compared with non-GNH tumors, GNH DPMs were associated with younger age and less frequent self-reported history of occupational asbestos exposure. Histologically, GNH DPMs were enriched in biphasic subtype (80% vs. 14.5%) and showed abundant tumor-infiltrating lymphocytes (TILs). Genomic analysis revealed a higher frequency of TP53 alterations, whereas SETDB1 mutations were present in nearly all and only in this subset. The clinicopathologic and molecular findings were further validated in a separate cohort. Despite the younger age, patients with GNH DPMs had a shorter overall survival (10.9 vs. 25.4 months, P = 0.004); the poor prognostic impact of GNH remained significant after controlling for biphasic histology. Of three patients with GNH DPMs who received immune checkpoint blockade, two achieved a clinician-assessed partial response.

CONCLUSIONS: GNH defines an aggressive subtype of mainly biphasic DPMs in younger patients with recurrent alterations in SETDB1 and TP53. The enrichment in biphasic histology and TILs, together with our preliminary immune checkpoint blockade response data and anecdotal clinical trial data, suggests that further evaluation of immunotherapy may be warranted in this subset.}, } @article {pmid38629360, year = {2024}, author = {Mirra, L and Beretta, GL and Lisini, D and Marcianti, A and Spampinato, E and Corno, C and Costantino, M and Corsico, A and Stella, GM and Perego, P}, title = {Therapeutic Strategies to Improve the Treatment of Pleural Mesothelioma.}, journal = {Current medicinal chemistry}, volume = {}, number = {}, pages = {}, doi = {10.2174/0109298673268206240405084558}, pmid = {38629360}, issn = {1875-533X}, abstract = {Pleural mesothelioma is a rare neoplastic disease with aggressive features. Patient survival is poor due to the lack of early symptoms and the absence of effective therapeutic strategies. The development of pleural mesothelioma is mainly associated with asbestos exposure and related chronic inflammation. From a molecular-based perspective, this disease is a heterogeneous tumor lacking actionable alterations. The median overall survival of patients affected by this tumor does not exceed 16 months from diagnosis. Molecular and biochemical approaches have shown that this disease is characterized by resistance to drug-induced apoptosis associated with the activation of cell survival pathways and expression of anti-apoptotic proteins. Thus, there is an urgent need to develop efficient and safe therapeutic strategies. Here, we review the pharmacological options available for the treatment of this disease with specific reference to the antitumor agents used in systemic therapies. In addition, novel pharmacological approaches, such as drug delivery tools, to improve pleural mesothelioma treatment are discussed.}, } @article {pmid38619810, year = {2024}, author = {Gibson, AEJ and Ahmed, W and Longworth, L and Bennett, B and Daumont, M and Darlison, L}, title = {Development of Patient and Caregiver Conceptual Models Investigating the Health-Related Quality of Life Impacts of Malignant Pleural Mesothelioma.}, journal = {The patient}, volume = {17}, number = {5}, pages = {551-563}, pmid = {38619810}, issn = {1178-1661}, mesh = {Humans ; *Quality of Life ; Male ; Female ; *Caregivers/psychology ; Middle Aged ; *Mesothelioma, Malignant/psychology ; Aged ; United Kingdom ; Qualitative Research ; Australia ; Pleural Neoplasms/psychology ; Interviews as Topic ; Adult ; Aged, 80 and over ; Lung Neoplasms/psychology ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare and usually fatal malignancy frequently linked to occupational asbestos exposures and associated with poor prognosis and considerable humanistic burden. The study aimed to develop conceptual models of the health-related quality of life (HRQoL) impact on patients with and receiving treatment for MPM, and the burden on their caregivers.

METHODS: This multi-country study (Australia and United Kingdom) adopted a qualitative methodology to conduct semi-structured, independent interviews with people with MPM (n = 26), current caregivers (n = 20), and caregivers of people who had recently died because of MPM (n = 4). Participants were recruited using a purposive sampling approach and interviews conducted via telephone between January 2021 and January 2022. Transcripts were analysed using thematic analysis and used to construct conceptual models.

RESULTS: Patient analysis yielded four overarching themes: (1) debilitating burden of breathlessness and fatigue; (2) physical mesothelioma symptoms experienced by patients; (3) distress of MPM on the self and family; and (4) treatment is worth 'having a go' despite the potential impact on symptoms. Caregiver analysis yielded five core themes: (1) daily life limited by caregiving duties; (2) emotional well-being and the need for support; (3) the relational role shift to caregiver; (4) time spent providing care negatively impacts work and productivity; and (5) positive aspects and outcomes of caregiving.

CONCLUSIONS: This study highlights the substantial daily and emotional HRQoL impact that MPM symptoms have on patients and caregivers. Both groups reduced work, productivity, and social and leisure activities. There was evidence of positive HRQoL impacts as a result of immunotherapy and radiotherapy, but less for chemotherapy. Caregiver impacts were intensified during the end-of-life period and persisted following patient death. Evident is a need for increased psychological support, information, and advice for caregivers, increased during the end-of-life period.}, } @article {pmid38619498, year = {2024}, author = {Miller, E and Beckett, EM and Cheatham, D and Comerford, CE and Lewis, RC and Krevanko, C and Mandava, N and Pierce, JS}, title = {A review of the mesotheliogenic potency of cleavage fragments found in talc.}, journal = {Toxicology and industrial health}, volume = {40}, number = {7}, pages = {398-424}, doi = {10.1177/07482337241246924}, pmid = {38619498}, issn = {1477-0393}, mesh = {*Talc/chemistry ; Humans ; Animals ; *Asbestos, Amphibole ; Mesothelioma/chemically induced ; Occupational Exposure/adverse effects ; }, abstract = {It has long been recognized that amphibole minerals, such as cleavage fragments of tremolite and anthophyllite, may exist in some talc deposits. We reviewed the current state of the science regarding the factors influencing mesotheliogenic potency of cleavage fragments, with emphasis on those that may co-occur in talc deposits, including dimensional and structural characteristics, animal toxicology, and the most well-studied cohort exposed to talc-associated cleavage fragments. Based on our review, multiple lines of scientific evidence demonstrate that inhaled cleavage fragments associated with talc do not pose a mesothelioma hazard.}, } @article {pmid38592450, year = {2024}, author = {Kadariya, Y and Sementino, E and Ruan, M and Cheung, M and Hadikhani, P and Osmanbeyoglu, HU and Klein-Szanto, AJ and Cai, K and Testa, JR}, title = {Low Exposures to Amphibole or Serpentine Asbestos in Germline Bap1-mutant Mice Induce Mesothelioma Characterized by an Immunosuppressive Tumor Microenvironment.}, journal = {Cancer research communications}, volume = {4}, number = {4}, pages = {1004-1015}, pmid = {38592450}, issn = {2767-9764}, support = {R00 CA207871/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Animals ; Mice ; *Mesothelioma, Malignant ; Asbestos, Serpentine ; Asbestos, Amphibole ; Asbestos, Crocidolite/toxicity ; Tumor Microenvironment/genetics ; *Mesothelioma/chemically induced ; *Neoplasms, Mesothelial ; Adenosine ; Immunosuppressive Agents ; Germ Cells ; }, abstract = {UNLABELLED: Asbestos and BAP1 germline mutations are risk factors for malignant mesothelioma (MM). While it is well accepted that amphibole asbestos is carcinogenic, the role of serpentine (chrysotile) asbestos in MM has been debated. To address this controversy, we assessed whether minimal exposure to chrysotile could significantly increase the incidence and rate of MM onset in germline Bap1-mutant mice. With either crocidolite or chrysotile, and at each dose tested, MMs occurred at a significantly higher rate and earlier onset time in Bap1-mutant mice than in wild-type littermates. To explore the role of gene-environment interactions in MMs from Bap1-mutant mice, we investigated proinflammatory and protumorigenic factors and the tumor immune microenvironment (TIME). IHC and immunofluorescence staining showed an increased number of macrophages in granulomatous lesions and MMs. The relative number of CD163-positive (CD163+) M2 macrophages in chrysotile-induced MMs was consistently greater than in crocidolite-induced MMs, suggesting that chrysotile induces a more profound immunosuppressive response that creates favorable conditions for evading immune surveillance. MMs from Bap1-mutant mice showed upregulation of CD39/CD73-adenosine and C-C motif chemokine ligand 2 (Ccl2)/C-C motif chemokine receptor 2 (Ccr2) pathways, which together with upregulation of IL6 and IL10, promoted an immunosuppressive TIME, partly by attracting M2 macrophages. Interrogation of published human MM RNA sequencing (RNA-seq) data implicated these same immunosuppressive pathways and connections with CD163+ M2 macrophages. These findings indicate that increased M2 macrophages, along with upregulated CD39/CD73-adenosine and Ccl2/Ccr2 pathways, contribute to an immunosuppressive TIME in chrysotile-induced MMs of Bap1-mutant mice, suggesting that immunotherapeutic strategies targeting protumorigenic immune pathways could be beneficial in human BAP1 mutation carriers who develop MM.

SIGNIFICANCE: We show that germline Bap1-mutant mice have enhanced susceptibility to MM upon minimal exposure to chrysotile asbestos, not only amphibole fibers. Chrysotile induced a more profound immune tumor response than crocidolite in Bap1-mutant mice by upregulating CD39/CD73-adenosine and Ccl2/Ccr2 pathways and recruiting more M2 macrophages, which together contributed to an immunosuppressive tumor microenvironment. Interrogation of human MM RNA-seq data revealed interconnected immunosuppressive pathways consistent with our mouse findings.}, } @article {pmid38583132, year = {2024}, author = {Stevens, ME and Paustenbach, DJ and Lockhart, NJ and Busboom, DE and Deckard, BM and Brew, DW}, title = {The presence of erionite in North American geologies and the estimated mesothelioma potency by region.}, journal = {Inhalation toxicology}, volume = {36}, number = {3}, pages = {158-173}, doi = {10.1080/08958378.2024.2322496}, pmid = {38583132}, issn = {1091-7691}, mesh = {Humans ; Asbestos, Crocidolite/toxicity ; Asbestos, Serpentine/toxicity ; Asbestos, Amosite/toxicity ; *Mesothelioma/chemically induced/epidemiology ; *Mesothelioma, Malignant/complications ; *Asbestos/toxicity ; *Zeolites ; Montana ; *Lung Neoplasms/epidemiology ; }, abstract = {OBJECTIVE: Erionite is a naturally occurring fibrous mineral found in soils in some geographical regions. Known for its potency for causing mesothelioma in the Cappadocia region of Turkey, the erionite fiber has attracted interest in the United States due to its presence in a band of rock that extends from Mexico to Montana. There are few toxicology studies of erionite, but all show it to have unusually high chronic toxicity. Despite its high potency compared to asbestos fibers, erionite has no occupational or environmental exposure limits. This paper takes what has been learned about the chemical and physical characteristics of the various forms of asbestos (chrysotile, amosite, anthophyllite, and crocidolite) and predicts the potency of North American erionite fibers.

MATERIALS AND METHODS: Based on the fiber potency model in Korchevskiy et al. (2019) and the available published information on erionite, the estimated mesothelioma potency factors (the proportion of mesothelioma mortality per unit cumulative exposure (f/cc-year)) for erionites in the western United States were determined.

RESULTS AND DISCUSSION: The model predicted potency factors ranged from 0.19 to 11.25 (average ∼3.5), depending on the region. For reference, crocidolite (the most potent commercial form of asbestos) is assigned a potency factor ∼0.5.

CONCLUSION: The model predicted mesothelioma potency of Turkish erionite (4.53) falls in this same range of potencies as erionite found in North America. Although it can vary by region, a reasonable ratio of average mesothelioma potency based on this model is 3,000:500:100:1 comparing North American erionite, crocidolite, amosite, and chrysotile (from most potent to least potent).}, } @article {pmid38552427, year = {2024}, author = {Lanfranco, A and Rakhshan, S and Alberti, D and Renzi, P and Zarechian, A and Protti, N and Altieri, S and Crich, SG and Deagostino, A}, title = {Combining BNCT with carbonic anhydrase inhibition for mesothelioma treatment: Synthesis, in vitro, in vivo studies of ureidosulfamido carboranes.}, journal = {European journal of medicinal chemistry}, volume = {270}, number = {}, pages = {116334}, doi = {10.1016/j.ejmech.2024.116334}, pmid = {38552427}, issn = {1768-3254}, mesh = {Mice ; Animals ; *Carbonic Anhydrases ; *Boron Neutron Capture Therapy ; *Mesothelioma/drug therapy ; *Glioma/drug therapy ; *Melanoma/drug therapy ; Boron Compounds/therapeutic use ; }, abstract = {Mesothelioma is a malignant neoplasm of mesothelial cells caused by exposure to asbestos. The average survival time after diagnosis is usually nine/twelve months. A multi-therapeutic approach is therefore required to treat and prevent recurrence. Boronated derivatives containing a carborane cage, a sulfamido group and an ureido functionality (CA-USF) have been designed, synthesised and tested, in order to couple Boron Neutron Capture Therapy (BNCT) and the inhibition of Carbonic Anhydrases (CAs), which are overexpressed in many tumours. In vitro studies showed greater inhibition than the reference drug acetazolamide (AZ). To increase solubility in aqueous media, CA-USFs were used as inclusion complexes of hydroxypropyl β-cyclodextrin (HP-β-CD) in all the inhibition and cell experiments. BNCT experiments carried out on AB22 (murine mesothelioma) cell lines showed a marked inhibition of cell proliferation by CA-USFs, and in one case a complete inhibition of proliferation twenty days after neutron irradiation. Finally, in vivo neutron irradiation experiments on a mouse model of mesothelioma demonstrated the efficiency of combining CA IX inhibition and BNCT treatment. Indeed, a greater reduction in tumour mass was observed in treated mice compared to untreated mice, with a significant higher effect when combined with BNCT. For in vivo experiments CA-USFs were administered as inclusion complexes of higher molecular weight β-CD polymers thus increasing the selective extravasation into tumour tissue and reducing clearance. In this way, boron uptake was maximised and CA-USFs demonstrated to be in vivo well tolerated at a therapeutic dose. The therapeutic strategy herein described could be expanded to other cancers with increased CA IX activity, such as melanoma, glioma, and breast cancer.}, } @article {pmid38538248, year = {2024}, author = {Mei, W and Zhang, YP and Yang, SJ}, title = {[Research progress on pathogenesis of malignant mesothelioma].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {42}, number = {3}, pages = {232-240}, doi = {10.3760/cma.j.cn121094-20221226-00604}, pmid = {38538248}, issn = {1001-9391}, support = {82160516//National Natural Science Foundation of China/ ; 2022J0716//Science Research Foundation of Education Department of Yunnan Province/ ; 202301BA070001-26, 202301BA070001-027//The Special Basic Cooperative Research Programs of Yunnan Provincial Undergraduate Universities/ ; }, mesh = {Humans ; *Mesothelioma, Malignant/complications ; *Lung Neoplasms/genetics/pathology ; *Pleural Neoplasms/genetics ; *Mesothelioma/genetics/diagnosis ; *Asbestos ; }, abstract = {The occurrence of malignant mesothelioma is related to exposure of asbestos. And many researchers have conducted in-depth analysis of the molecular changes of mesothelioma, showed that its molecular characteristics were chromosome changes, including chromosome rearrangement, gene mutation and gene deletion. Recent studies have strengthened our understanding of molecular characterization of mesothelioma, such as targeted mutations of tumor suppressor genes, differential gene expression, changes of miRNA and signal pathways. It is of great significance for the early diagnosis, clinical treatment and prognosis of malignant mesothelioma to explore the pathogenesis and development of malignant mesothelioma. This article reviews the research progress on the pathogenesis and carcinogenesis-related molecules of malignant mesothelioma.}, } @article {pmid38538239, year = {2024}, author = {Wang, ZZ and Zhang, JJ and Song, PP and Zhang, H and Luo, LM and Luan, T}, title = {[Survival analysis of 37 cases of malignant mesothelioma].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {42}, number = {3}, pages = {191-195}, doi = {10.3760/cma.j.cn121094-20230109-00012}, pmid = {38538239}, issn = {1001-9391}, mesh = {Humans ; Aged ; Middle Aged ; *Mesothelioma, Malignant ; *Mesothelioma/drug therapy ; Retrospective Studies ; *Pleural Neoplasms ; Prognosis ; Survival Analysis ; *Lung Neoplasms ; Survival Rate ; }, abstract = {Objective: To explore the relationship between clinicopathological features, treatment and prognosis of patients with malignant mesothelioma, and provide theoretical basis for the prevention and treatment of malignant mesothelioma. Methods: In November 2022, the clinical data of 37 patients with malignant mesothelioma diagnosed in Qingdao Central Hospital from July 2014 to November 2022 were retrospectively analyzed, and the prognostic factors were analyzed by Kaplan-Meier and log-rank tests. Results: The median age of the 37 patients was 66 years old, all patients were confirmed by pathology. The median survival time of all patients was 30.00 months. The 1-year, 2-year, 3-year and 5-year cumulative survival rates were 70.27% (26/37), 48.65% (18/37), 16.22% (6/37) and 13.51% (5/37), respectively. Compared with different treatments, the median survival time of palliative care patients was 5.00 months, which was significantly lower than that of operation group (30.33 months), chemotherapy group (30.00 months), surgery combined with chemotherapy group (30.00 months) and chemotherapy combined with bevacizumab targeted therapy group (47.42 months) (P<0.05). Gender, age (≥60 years old or <60 years old), smoking history, occupational exposure history, disease site, and surgical history were not factors affecting the survival of malignant mesothelioma patients (P>0.05) . Conclusion: The clinical symptoms of malignant mesothelioma are not specific, but early initiation of treatment can still prolong survival, and chemotherapy combined with anti-vascular targeted therapy shows better therapeutic effect.}, } @article {pmid38532179, year = {2024}, author = {Mirabelli, D and Somigliana, AB and Azzolina, D and Consonni, D and Barbieri, PG}, title = {Lung fibre burden and risk of malignant mesothelioma in shipyard workers: a necropsy-based case-control study.}, journal = {Annals of work exposures and health}, volume = {68}, number = {5}, pages = {476-485}, doi = {10.1093/annweh/wxae018}, pmid = {38532179}, issn = {2398-7316}, mesh = {Humans ; Male ; Case-Control Studies ; *Occupational Exposure/adverse effects ; *Mesothelioma/pathology/etiology/epidemiology ; Italy/epidemiology ; Middle Aged ; *Lung Neoplasms/pathology/etiology/epidemiology ; *Ships ; Aged ; *Mesothelioma, Malignant ; Mineral Fibers/analysis/adverse effects ; Occupational Diseases/epidemiology/etiology ; Lung/pathology ; Pleural Neoplasms/etiology/pathology/epidemiology ; Adult ; Odds Ratio ; Autopsy ; Asbestos/analysis/adverse effects ; Asbestos, Amphibole/analysis/adverse effects ; Asbestos, Serpentine/analysis/adverse effects ; Risk Factors ; }, abstract = {OBJECTIVES: In Italy, the highest pleural cancer mortality and incidence have been observed among Italian regions where the 2 largest Italian shipyards were (and are) located. The objective of this study was to assess the exposure-response relationship for mesothelioma among male workers employed in the Monfalcone, Italy, shipyard.

METHODS: We conducted a necropsy-based case-control study. Cases (N = 102) were mesothelioma decedents and controls were those with lung cancer (N = 84). Complete job histories were available; the lung fibre content was measured using a scanning electron microscope with X-ray fluorescence, after sample preparation according to the European Respiratory Society guidelines. Odds ratios and 95% confidence intervals of mesothelioma by fibre type and lung fibre burden, as a categorical or continuous variable, were assessed by unconditional logistic regression, adjusted for age and time since exposure cessation. Analyses for the amphibole and chrysotile lung fibre burden were mutually adjusted. We calculated a cumulative exposure index by applying a job-exposure matrix to the job histories of study cases and assessed its correlation with the lung fibre burden.

RESULTS: We found an odds ratio of 22.0 (confidence intervals 5.66-85.7) for the highest lung fibre burden category (mean 43.8 million total asbestos fibres per gram of dry tissue) compared with the reference (mean 0.48). Using log10-transformed lung fibre burden, we found that the odds ratio was 3.71 (confidence intervals 2.03-6.79) for a 10-fold lung fibre burden increase. Results for the amphibole lung fibre burden were similar. Odds ratios increased over chrysotile lung fibre burden categories (P-trend = 0.025), and the odds ratio for a 10-fold increase was 4.73 (confidence intervals 0.32-70.4).

CONCLUSIONS: The cumulative exposure index was correlated with total and amphibole lung fibre burden, but not with chrysotile lung fibre burden. Mesothelioma risk was proportional to total, amphibole, and chrysotile lung fibre burden in shipyard workers.}, } @article {pmid38522452, year = {2024}, author = {Burki, T}, title = {EPA ruling to ban chrysotile asbestos.}, journal = {The Lancet. Oncology}, volume = {25}, number = {5}, pages = {537}, doi = {10.1016/S1470-2045(24)00155-4}, pmid = {38522452}, issn = {1474-5488}, mesh = {*Asbestos, Serpentine/adverse effects ; Humans ; *United States Environmental Protection Agency/legislation & jurisprudence ; United States ; Mesothelioma/chemically induced ; Occupational Exposure/legislation & jurisprudence/adverse effects/prevention & control ; Lung Neoplasms ; }, } @article {pmid38522172, year = {2024}, author = {Sherborne, V and Wood, E and Mayland, CR and Gardiner, C and Lusted, C and Bibby, A and Tod, A and Taylor, B and Ejegi-Memeh, S}, title = {The mental health and well-being implications of a mesothelioma diagnosis: A mixed methods study.}, journal = {European journal of oncology nursing : the official journal of European Oncology Nursing Society}, volume = {70}, number = {}, pages = {102545}, doi = {10.1016/j.ejon.2024.102545}, pmid = {38522172}, issn = {1532-2122}, mesh = {Humans ; Male ; Female ; *Mesothelioma/diagnosis/psychology ; Cross-Sectional Studies ; Middle Aged ; Aged ; *Quality of Life ; *Caregivers/psychology ; Adult ; Mental Health ; Depression/epidemiology/diagnosis ; Anxiety/epidemiology/diagnosis ; Aged, 80 and over ; Stress Disorders, Post-Traumatic/diagnosis/epidemiology ; Surveys and Questionnaires ; Mesothelioma, Malignant/diagnosis ; }, abstract = {PURPOSE: Mesothelioma is an incurable, asbestos-related cancer with a poor prognosis. There is scant evidence about the mental health and well-being impacts on patients and carers living with the illness. This study aimed to investigate mesothelioma's impact on mental health and well-being and the scale of mental health conditions in patients and informal carers.

METHODS: A mixed-methods design was used: a cross-sectional survey of mesothelioma patients and informal carers plus semi-structured interviews with patients and carers. The survey used validated scales collecting data on mental health aspects of mesothelioma: the EQ5D to assess health-related quality-of-life; the Hospital Anxiety and Depression scale; the PCL-5 to assess Posttraumatic Stress; and the Posttraumatic Growth Inventory. The datasets were integrated during analysis.

RESULTS: 96 useable survey responses were received. A clinical level of depression was reported by 29 participants (30.21%), of anxiety by 48 (50%), of posttraumatic distress disorder by 32 (33.33%), and of posttraumatic growth by 34 (35.42%). Carers had worse scores than patients. Three main themes were developed from interviews with 10 patients and 11 carers: 'Prognosis', 'Support from services', and 'Social connections and communication'.

CONCLUSIONS: Healthcare professionals delivering a mesothelioma diagnosis require regular training in communication skills plus updating in current treatment options, so they provide an appropriate mix of realism and hope. Better signposting to mental health support is needed for patients and carers. Our introduction of posttraumatic growth into the mesothelioma literature is novel. We recommend specialist nurses are trained to recognise, understand, and foster posttraumatic growth.}, } @article {pmid38521202, year = {2024}, author = {Gill, RR and Nowak, AK and Giroux, DJ and Eisele, M and Rosenthal, A and Kindler, H and Wolf, A and Ripley, RT and Billé, A and Rice, D and Opitz, I and Rimner, A and de Perrot, M and Pass, HI and Rusch, VW and , }, title = {The International Association for the Study of Lung Cancer Mesothelioma Staging Project: Proposals for Revisions of the "T" Descriptors in the Forthcoming Ninth Edition of the TNM Classification for Pleural Mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {19}, number = {9}, pages = {1310-1325}, pmid = {38521202}, issn = {1556-1380}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Neoplasm Staging/standards/methods ; *Pleural Neoplasms/pathology/classification ; *Lung Neoplasms/pathology/classification ; Male ; Female ; *Mesothelioma/pathology/classification ; Aged ; Middle Aged ; Mesothelioma, Malignant/pathology/classification ; Prognosis ; Prospective Studies ; }, abstract = {INTRODUCTION: The primary tumor (T) component in the eighth edition of pleural mesothelioma (PM) staging system is based on pleural involvement and extent of invasion. Quantitative assessment of pleural tumor has been found to be prognostic. We explored quantitative and qualitative metrics to develop recommendations for T descriptors in the upcoming ninth edition of the PM staging system.

METHODS: The International Association for the Study of Lung Cancer prospectively collected data on patients with PM. Sum of maximum pleural thickness (Psum) was recorded. Optimal combinations of Psum and eighth edition cT descriptors were assessed using recursive binary splitting algorithm, with bootstrap resampling to correct for the adaptive nature of the splitting algorithm, and validated in the eighth edition data. Overall survival (OS) was calculated by the Kaplan-Meier method and differences in OS assessed by the log-rank test.

RESULTS: Of 7338 patients submitted, 3598 were eligible for cT analysis and 1790 had Psum measurements. Recursive partitioning identified optimal cutpoints of Psum at 12 and 30 mm, which, in combination with extent of invasion, yielded four prognostic groups for OS. Fmax greater than 5 mm indicated poor prognosis. cT4 category (based on invasion) revealed similar performance to eighth edition. Three eighth edition descriptors were eliminated based on low predictive accuracy. Eighth edition pT descriptors remained valid in ninth edition analyses.

CONCLUSION: Given reproducible prognostication by Psum, size criteria will be incorporated into cT1 to T3 categories in the ninth edition. Current cT4 category and all pT descriptors will be maintained, with reclassification of fissural invasion as pT2.}, } @article {pmid38515807, year = {2023}, author = {Singh, S and Roy Pradhan, S and Yadav, A and Singh, PK}, title = {Banning asbestos in talcum powder: Time for action in India.}, journal = {Dialogues in health}, volume = {3}, number = {}, pages = {100158}, pmid = {38515807}, issn = {2772-6533}, abstract = {Long-term use of asbestos-contaminated talcum power has been reported to be the main causative agent for carcinogenesis in many research studies. In recent developments Johnson & Johnson has lost multimillion-dollar lawsuits for being associated with the development of mesothelioma and ovarian cancer by its talc-based baby powder. In May 2020, the company announced, the end of the sale of its baby powder in the USA and Canada and in August 2022, announced the global discontinuation by 2023. However, in India vast proportions of people are using talc-based baby powder and the products are readily available in the market. The purpose of this communication is to create awareness and draw attention of authorities for effective regulation, including prohibition of sale and retraction of the contaminated talc-based products from the Indian market at the earliest.}, } @article {pmid38511037, year = {2024}, author = {Singh, A and Bansal, C and Singla, D and More, S and Chabhra, S and Bashir, S}, title = {Peritoneal Malignant Mesothelioma Metastasizing to Lymph Node in Young Male-a Case Report.}, journal = {Indian journal of surgical oncology}, volume = {15}, number = {1}, pages = {145-148}, pmid = {38511037}, issn = {0975-7651}, abstract = {Peritoneal malignant mesothelioma is an uncommon neoplasm with a poor prognosis. We hereby report a case of a 20-year-old male, first diagnosed on biopsy with axillary lymph node metastasis. He presented with abdominal pain and axillary lymphadenopathy, with no history of asbestos exposure. CECT showed peritoneal thickening and ascites. Ascitic fluid cytology showed reactive morphology. The diagnosis of metastatic deposits of malignant mesothelioma was made on histopathology and confirmed by immunohistochemistry. Tumor cells were immune-reactive for CK 5/6, calretinin, D2-40, and WT1 and negative for TTF1, CK 20, and CD 3. This case report has two important highlights-(i) unusual presentation with axillary lymph node metastasis leading to diagnostic dilemma in a young male with no asbestos exposure history and (ii) confirmatory diagnostic role of IHC in Peritoneal malignant mesothelioma.}, } @article {pmid38505910, year = {2024}, author = {Tuncel, T and Ak, G and Güneş, HV and Metintaş, M}, title = {Complex Genomic Rearrangement Patterns in Malignant Pleural Mesothelioma due to Environmental Asbestos Exposure.}, journal = {Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer}, volume = {43}, number = {2}, pages = {13-27}, doi = {10.1615/JEnvironPatholToxicolOncol.2023046200}, pmid = {38505910}, issn = {2162-6537}, mesh = {Humans ; *Mesothelioma, Malignant/genetics/complications ; *Mesothelioma/chemically induced/genetics ; *Lung Neoplasms/chemically induced/genetics ; *Asbestos/toxicity ; Genomics ; Nucleotides ; Xeroderma Pigmentosum Group D Protein ; X-ray Repair Cross Complementing Protein 1 ; DEAD-box RNA Helicases ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare type of cancer, and its main risk factor is exposure to asbestos. Accordingly, our knowledge of the genomic structure of an MPM tumor is limited when compared to other cancers. In this study, we aimed to characterize complex genomic rearrangement patterns and variations to better understand the genomics of MPM tumors. We comparatively scanned 3 MPM tumor genomes by Whole-Genome Sequencing and High-Resolution SNP array. We also used various computational algorithms to detect both CNAs and complex chromosomal rearrangements. Genomic data obtained from each bioinformatics tool are interpreted comparatively to better understand CNAs and cancer-related Nucleotide variations in MPM tumors. In patients 1 and 2, we found pathogenic nucleotide variants of BAP1, RB1, and TP53. These two MPM genomes exhibited a highly rearranged chromosomal rearrangement pattern resembling Chromomanagesis particularly in the form of Chromoanasynthesis. In patient 3, we found nucleotide variants of important cancer-related genes, including TGFBR1, KMT2C, and PALLD, to have lower chromosomal rearrangement complexity compared with patients 1 and 2. We also detected several actionable nucleotide variants including XRCC1, ERCC2. We also discovered the SKA3-DDX10 fusion in two MPM genomes, which is a novel finding for MPM. We found that MPM genomes are very complex, suggesting that this highly rearranged pattern is strongly related to driver mutational status like BAP1, TP53 and RB1.}, } @article {pmid38502527, year = {2024}, author = {Rota, M and Viscardi, A and Maghin, F and Placidi, D and Conti, A}, title = {Mesothelioma among seamen: a systematic review and meta-analysis.}, journal = {European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP)}, volume = {33}, number = {5}, pages = {438-447}, doi = {10.1097/CEJ.0000000000000875}, pmid = {38502527}, issn = {1473-5709}, mesh = {Humans ; *Mesothelioma/epidemiology/mortality/etiology ; *Occupational Exposure/adverse effects ; *Asbestos/adverse effects/toxicity ; *Ships ; Occupational Diseases/epidemiology/etiology/mortality ; Military Personnel/statistics & numerical data ; }, abstract = {OBJECTIVES: Navy personnel and seafarers live and work 24 h per day in the shipboard environment and they are exposed to asbestos fibers released into the confined spaces aboard ships. We conducted a systematic review and meta-analysis to quantify the mesothelioma risk of seamen working aboard ships, either commercial or naval vessels, as compared to that of the general population.

METHODS: We carried out a literature search in MEDLINE through PubMed and EMBASE, from inception to 31 December 2021, of all studies on seamen working aboard ships, either commercial or naval vessels, characterized by exposure to asbestos and providing mesothelioma risk estimates. The Newcastle-Ottawa Scale was used to assess the quality of the studies included. The pooled standardized mortality ratio (SMR) was computed across eligible studies. The study protocol was registered on PROSPERO and reporting followed the preferred reporting items for systematic reviews and meta-analyses guidelines.

RESULTS: A total of 10 studies published from 1990 to 2020 were considered eligible and included in the systematic review and meta-analysis. All the included studies were of good quality, with a median score of seven out of nine. Overall, there were 235 mesothelioma cases/deaths in the included studies versus 115.6 expected, with a pooled SMR of 2.11 (95% confidence intervals, 1.70-2.62), in the absence of a significant between-study heterogeneity (I2  = 39%, P  = 0.11).

CONCLUSION: A more than double excess risk for mesothelioma among seamen working aboard ships emerged from our meta-analysis.}, } @article {pmid38502172, year = {2024}, author = {Dodson, RF and Moline, J and Salinas, CD and Poye, LW}, title = {Elongated particulate burden in an individual who died of mesothelioma and had an occupational history as a talc "mucker".}, journal = {Inhalation toxicology}, volume = {36}, number = {3}, pages = {205-216}, doi = {10.1080/08958378.2024.2329935}, pmid = {38502172}, issn = {1091-7691}, mesh = {Male ; Humans ; Aged ; Talc ; *Mesothelioma/chemically induced ; Asbestos, Amphibole ; *Mesothelioma, Malignant/complications ; *Asbestos/toxicity ; *Lung Neoplasms/chemically induced ; Dust ; }, abstract = {INTRODUCTION: Tissue from a 77-year-old man diagnosed with mesothelioma was referred with a request for identification of the presence of fibrous structures in tissue samples. The individual's work history including working as a "mucker" at a specific "industrial" talc mine.

METHODS: Ferruginous bodies in the tissue digests as well as asbestos fibers were found. A bulk sample of a talc containing product from that mine was also analyzed.

DISCUSSIONS/CONCLUSIONS: The correlation between the unique asbestos mineral/fibrous content of the talc to which he was exposed and findings of the same type of asbestos found in his lung is discussed. The type of asbestos found (tremolite) is a "non-commercial" type of asbestos that has been identified in some talc deposits. Tremolite, like all forms of asbestos is a causative agent for mesothelioma-the disease from which this individual suffered.}, } @article {pmid38500093, year = {2024}, author = {Miao, X and Yao, T and Dong, C and Chen, Z and Wei, W and Shi, Z and Xu, T and Shao, J and Niu, Q and Rui, D and Hu, Y and Yan, Y}, title = {Global, regional, and national burden of non-communicable diseases attributable to occupational asbestos exposure 1990-2019 and prediction to 2035: worsening or improving?.}, journal = {BMC public health}, volume = {24}, number = {1}, pages = {832}, pmid = {38500093}, issn = {1471-2458}, support = {RCZK2021B28//The Shihezi University High-level Talents Program/ ; ZZZC202125//The Shihezi University self-funded project/ ; SRP2023085//The Shihezi University 2023 College Student Research and Training Program SRP Project/ ; }, mesh = {Male ; Humans ; Aged ; Quality-Adjusted Life Years ; *Noncommunicable Diseases/epidemiology ; Global Burden of Disease ; *Occupational Exposure/adverse effects ; *Asbestos/toxicity ; Global Health ; }, abstract = {Understanding the burden associated with occupational asbestos exposure on a global and regional scale is necessary to implement coordinated prevention and control strategies. By the GBD Study 2019, we conducted a comprehensive assessment of the non-communicable diseases burden attributable to occupational asbestos exposure. In 2019, 239,330 deaths and 4,189,000 disability-adjusted life years (DALYs) worldwide due to occupational asbestos exposure occurred. 1990-2019, deaths and DALYs attributed to occupational asbestos exposure increased by 65.65% and 43.66%, respectively. Age-standardized mortality rate (ASMR) and age-standardized DALYs rate (ASDR) decreased, with the most rapid declines in high Socio-Demographic Index (SDI) regions, with average annual percent change (AAPC) of - 1.05(95%CI: -1.2, -0.89) and -1.53(95%CI: -1.71, -1.36), respectively. Lung cancer, mesothelioma and ovarian cancer were the top three contributors to the increase in deaths and DALYs, accounting for more than 96%. AAPCs of ASMR and ASDR were positively associated with SDI. Global deaths from occupational asbestos exposure were predicted to increase and ASMR to decrease by 2035, mostly in males. Due consideration should be given to the susceptibility of the elderly, the lag of asbestos onset, and the regional differences, and constantly improve the prevention and control measures of occupational asbestos exposure and related diseases.}, } @article {pmid38490630, year = {2024}, author = {Frank, AL}, title = {To the Editor-environmental research this letter is a critique of the paper by regarding chronological trends of the fiber burden in mesothelioma cases.}, journal = {Environmental research}, volume = {251}, number = {Pt 1}, pages = {117352}, doi = {10.1016/j.envres.2023.117352}, pmid = {38490630}, issn = {1096-0953}, mesh = {Humans ; *Mesothelioma/epidemiology ; Asbestos ; }, } @article {pmid38482789, year = {2024}, author = {Chellini, E}, title = {[Is the epidemiological surveillance of malignant mesothelioma implemented in Italy still valid and necessary?].}, journal = {Epidemiologia e prevenzione}, volume = {48}, number = {1}, pages = {78-84}, doi = {10.19191/EP24.1.A561.024}, pmid = {38482789}, issn = {1120-9763}, mesh = {Humans ; *Mesothelioma, Malignant ; *Mesothelioma/epidemiology/etiology ; *Occupational Exposure ; *Pleural Neoplasms/epidemiology/etiology ; Italy/epidemiology ; *Asbestos/toxicity ; }, abstract = {The register of malignant mesotheliomas can still play an informative role in the context of both remediation activities and the health surveillance of former asbestos-exposed persons, and become an epidemiological surveillance system on the harmful effects of exposure to asbestos. It must, however, maintain and improve the level of quality achieved, resolve the problems that have emerged in the interaction between the local level (where cases and their exposure histories are identified, registered, assessed, and medical insurance procedures activated) and the central insurance body that also manages the national register, and become an active participant in research, including clinical research. All this is important to meet the social and welfare justice needs of individual cases.}, } @article {pmid38465395, year = {2024}, author = {Costantino, C and Ledda, C and Riccò, M and Costagliola, E and Balsamo, F and Belluzzo, M and Bonaccorso, N and Carubia, A and D'Azzo, L and Sciortino, M and Vitello, T and Zagra, L and Fruscione, S and Ilardo, S and Trapani, E and Calamusa, G and Rapisarda, V and Mazzucco, W}, title = {Decade-long insights: tracking asbestos-related health impacts among formerly exposed workers in Palermo, Italy.}, journal = {Annali di igiene : medicina preventiva e di comunita}, volume = {36}, number = {5}, pages = {525-536}, doi = {10.7416/ai.2024.2619}, pmid = {38465395}, issn = {1120-9135}, mesh = {Humans ; Italy/epidemiology ; *Occupational Exposure/adverse effects ; *Asbestosis/epidemiology/etiology ; *Asbestos/adverse effects ; Male ; *Lung Neoplasms/epidemiology/etiology ; Middle Aged ; Female ; Aged ; *Occupational Diseases/epidemiology/etiology ; Mesothelioma/epidemiology/etiology ; Adult ; Time Factors ; Pleural Neoplasms/epidemiology/etiology ; Smoking/epidemiology/adverse effects ; }, abstract = {BACKGROUND: Asbestos is a foremost occupational carcinogen globally. Despite the prohibition under Law 257/1992, Italy persists as one of the European nations most burdened by asbestos-related diseases (ARDs). This research assessed ARD cases in asbestos-exposed workers from the Province of Palermo, Italy, spanning 2010-2021.

METHODS: Data acquisition utilized the epidemiological dataset from the 'Service of Prevention and Safety on Work Environment' under the Prevention Department of Palermo's Local Health Authority (LHA).

RESULTS: Between 2010 and 2021, we identified 245 ARD instances, comprising 163 Asbestosis/Pleural plaques, 41 Lung Cancers, 38 Mesotheliomas, and 3 unspecified cases. Multivariate analysis indicated a notable decline in temporal exposure for mesothelioma (HR=0.933; 95% CI=0.902-0.965) and lung cancer (HR=0.93; 95% CI=0.90-0.978) relative to pleural plaques/asbestosis. Tobacco use displayed a pronounced correlation with lung cancer (smoker HR=64.520 95% CI=13,075-318.390; former smoker HR=20.917 95% CI=4,913-89.048). A significant link was observed between mesothelioma and pleural plaques/asbestosis in those employed in shipbuilding and repair (HR=0.371 95% CI=0.155-0.892).

CONCLUSIONS: ARDs persist in clinical observations, even following the 1992 cessation of asbestos-related activities, emphasizing an enduring public health challenge. Enhancing prevention strategies is paramount, focusing on amplifying anamnestic and occupational data collection, thereby facilitating superior early diagnosis strategies for these maladies in the occupationally exposed cohort.}, } @article {pmid38462627, year = {2024}, author = {Liu, J and Lu, Y and Liu, Y and Zhang, W and Xian, S and Wang, S and Zheng, Z and Lin, R and Jin, M and Zhang, M and Qian, W and Tang, J and Lu, B and Yang, Y and Liu, Z and Qu, M and Ma, H and Wu, X and Chang, Z and Zhang, J and Zhang, Y}, title = {A gene signature linked to fibroblast differentiation for prognostic prediction of mesothelioma.}, journal = {Cell & bioscience}, volume = {14}, number = {1}, pages = {33}, pmid = {38462627}, issn = {2045-3701}, support = {82002923//National Natural Science Foundation of China/ ; 201940306//Shanghai Municipal Health Commission/ ; }, abstract = {BACKGROUND: Malignant mesothelioma is a type of infrequent tumor that is substantially related to asbestos exposure and has a terrible prognosis. We tried to produce a fibroblast differentiation-related gene set for creating a novel classification and prognostic prediction model of MESO.

METHOD: Three databases, including NCBI-GEO, TCGA, and MET-500, separately provide single-cell RNA sequencing data, bulk RNA sequencing profiles of MESO, and RNA sequencing information on bone metastatic tumors. Dimensionality reduction and clustering analysis were leveraged to acquire fibroblast subtypes in the MESO microenvironment. The fibroblast differentiation-related genes (FDGs), which were associated with survival and subsequently utilized to generate the MESO categorization and prognostic prediction model, were selected in combination with pseudotime analysis and survival information from the TCGA database. Then, regulatory network was constructed for each MESO subtype, and candidate inhibitors were predicted. Clinical specimens were collected for further validation.

RESULT: A total of six fibroblast subtypes, three differentiation states, and 39 FDGs were identified. Based on the expression level of FDGs, three MESO subtypes were distinguished in the fibroblast differentiation-based classification (FDBC). In the multivariate prognostic prediction model, the risk score that was dependent on the expression level of several important FDGs, was verified to be an independently effective prognostic factor and worked well in internal cohorts. Finally, we predicted 24 potential drugs for the treatment of MESO. Moreover, immunohistochemical staining and statistical analysis provided further validation.

CONCLUSION: Fibroblast differentiation-related genes (FDGs), especially those in low-differentiation states, might participate in the proliferation and invasion of MESO. Hopefully, the raised clinical subtyping of MESO would provide references for clinical practitioners.}, } @article {pmid38459714, year = {2024}, author = {Rigon, M and Mutti, L and Campanella, M}, title = {Pleural mesothelioma (PMe): The evolving molecular knowledge of a rare and aggressive cancer.}, journal = {Molecular oncology}, volume = {18}, number = {4}, pages = {797-814}, pmid = {38459714}, issn = {1878-0261}, support = {2019//Gruppo Italiano Mesotelioma G.I.Me Charity/ ; COG2018-819600_FIRM//H2020 European Research Council/ ; ARCLEADER2022020004901//Fondation ARC pour la Recherche sur le Cancer/ ; MFAG21903//Associazione Italiana per la Ricerca sul Cancro/ ; }, mesh = {Humans ; *Mesothelioma/genetics/diagnosis ; *Mesothelioma, Malignant ; *Pleural Neoplasms/genetics ; *Asbestos ; *Lung Neoplasms/pathology ; }, abstract = {Mesothelioma is a type of late-onset cancer that develops in cells covering the outer surface of organs. Although it can affect the peritoneum, heart, or testicles, it mainly targets the lining of the lungs, making pleural mesothelioma (PMe) the most common and widely studied mesothelioma type. PMe is caused by exposure to fibres of asbestos, which when inhaled leads to inflammation and scarring of the pleura. Despite the ban on asbestos by most Western countries, the incidence of PMe is on the rise, also facilitated by a lack of specific symptomatology and diagnostic methods. Therapeutic options are also limited to mainly palliative care, making this disease untreatable. Here we present an overview of biological aspects underlying PMe by listing genetic and molecular mechanisms behind its onset, aggressive nature, and fast-paced progression. To this end, we report on the role of deubiquitinase BRCA1-associated protein-1 (BAP1), a tumour suppressor gene with a widely acknowledged role in the corrupted signalling and metabolism of PMe. This review aims to enhance our understanding of this devastating malignancy and propel efforts for its investigation.}, } @article {pmid38447601, year = {2024}, author = {Roggli, VL and Pavlisko, EN and Glass, CH and Green, CL and Liu, B and Carney, JM}, title = {Response to the editor-Environmental Research this letter is a critique of the paper by Roggli et al. (1) regarding chronological trends of the fiber burden in mesothelioma cases.}, journal = {Environmental research}, volume = {251}, number = {Pt 1}, pages = {118620}, doi = {10.1016/j.envres.2024.118620}, pmid = {38447601}, issn = {1096-0953}, mesh = {Humans ; *Mesothelioma/epidemiology/chemically induced ; Asbestos ; }, } @article {pmid38447379, year = {2024}, author = {Haakensen, VD and Öjlert, ÅK and Thunold, S and Farooqi, S and Nowak, AK and Chin, WL and Grundberg, O and Szejniuk, WM and Cedres, S and Sørensen, JB and Dalen, TS and Lund-Iversen, M and Bjaanæs, M and Helland, Å}, title = {UV1 telomerase vaccine with ipilimumab and nivolumab as second line treatment for pleural mesothelioma - A phase II randomised trial.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {202}, number = {}, pages = {113973}, doi = {10.1016/j.ejca.2024.113973}, pmid = {38447379}, issn = {1879-0852}, mesh = {Humans ; Nivolumab/adverse effects ; Ipilimumab/adverse effects ; *Telomerase ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; *Mesothelioma, Malignant/drug therapy ; *Mesothelioma/drug therapy ; *Pleural Neoplasms/drug therapy/etiology ; }, abstract = {PURPOSE: The NIPU-trial investigates the effect of adding the telomerase vaccine UV1 to treatment with ipilimumab and nivolumab for patients with pleural mesothelioma (PM).

METHODS: In this phase 2 open-label trial, patients with PM progressing after first-line chemotherapy were randomised to receive ipilimumab and nivolumab alone (arm B) or combined with UV1 (arm A). The primary endpoint was progression-free survival (PFS) as determined by BICR. It was estimated that 69 PFS events were needed to detect a hazard ratio (HR) of 0.60 with 80% power and a one-sided alpha level of 0.10.

RESULTS: 118 patients were randomised. The median PFS determined by blinded independent central review (BICR) was 4.2 months (95%CI 2.9-9.8) in arm A and 4.7 months (95%CI 3.9-7.0) in arm B (HR 1.01, 80%CI 0.75-1.36 P = 0.979), after a median follow-up of 12.5 months (95%CI 9.7-15.6). The investigator-determined median PFS was 4.3 months (95%CI 3.0-6.8) in arm A and 2.9 months (95%CI 2.4-5.5) in arm B (HR 0.60, 80%CI 0.45-0.81 P = 0.025). Confirmed objective response rate (ORR) by BICR was 31% in arm A and 16% in arm B (odds ratio 2.44 80%CI 1.35-4.49 P = 0.056). After a median follow-up time of 17.3 months (95%CI 15.8-22.9), the OS was 15.4 months (95%CI 11.1-22.6) in arm A and 11.1 months (95%CI 8.8-18.1) in arm B, (HR 0.73, 80%CI 0.53-1.0, P = 0.197).

CONCLUSION: The primary endpoint was not met. Predefined analyses of response rates are in favour of adding the vaccine.}, } @article {pmid38426158, year = {2024}, author = {Amakusa, Y and Suzuki, T and Hikosaka, Y and Takemura, M and Oguri, T}, title = {Successful treatment of simultaneous malignant pleural mesothelioma and pulmonary adenocarcinoma: A case report.}, journal = {Oncology letters}, volume = {27}, number = {4}, pages = {155}, pmid = {38426158}, issn = {1792-1082}, abstract = {The present report described the case of a 74-year-old male patient with asbestos exposure whose chest computed tomography revealed a right lower lobe nodule and right pleural effusion. Pleural biopsy led to the diagnosis of epithelial malignant pleural mesothelioma (cT2N0M0, stage IB). Combination therapy with cisplatin + pemetrexed led to the complete remission of malignant pleural mesothelioma; however, the right lower lobe nodule grew in size over time. The patient was subsequently diagnosed with lung adenocarcinoma (cT1aN0M0, stage IA1) by computed tomography-guided biopsy performed 18 months after chemotherapy initiation and achieved remission of lung adenocarcinoma with stereotactic radiotherapy. The patient was alive without recurrence at the 12-month follow-up. The present case illustrated that multiple active regimens are currently available for malignant pleural mesothelioma and lung cancer that can aid in the treatment of complex cases.}, } @article {pmid38423601, year = {2024}, author = {Shimizu, D and Ishibashi, M and Yamada, T and Toda, Y and Hosogi, S and Ashihara, E}, title = {POLD1 Is Required for Cell Cycle Progression by Overcoming DNA Damage in Malignant Pleural Mesothelioma.}, journal = {Cancer genomics & proteomics}, volume = {21}, number = {2}, pages = {158-165}, pmid = {38423601}, issn = {1790-6245}, mesh = {Humans ; *Mesothelioma, Malignant ; DNA Polymerase III/genetics ; *Lung Neoplasms/pathology ; *Pleural Neoplasms/genetics/pathology ; *Mesothelioma/genetics ; RNA, Small Interfering/genetics ; Cell Line, Tumor ; Cell Cycle/genetics ; DNA Damage ; RNA, Messenger ; }, abstract = {BACKGROUND/AIM: The prognosis of patients with malignant pleural mesothelioma (MPM) remains poor due to lack of effective therapeutic targets. DNA damage caused by long-time exposure to asbestos fibers has been associated with the development of MPM, with mutations at genes encoding DNA damage repair (DDR)-related molecules frequently expressed in patients with MPM. The present study was designed to identify novel therapeutic targets in MPM using large public databases, such as The Cancer Genome Atlas (TCGA) and Genotype Tissue Expression project (GTEx) focused on DDR pathways.

MATERIALS AND METHODS: The correlations between mRNA expression levels of DDR-related genes and overall survival (OS) were analyzed in mesothelioma patients in TCGA mesothelioma (TCGA-MESO) datasets. The anti-tumor effects of small interfering RNAs (siRNA) against DDR-related genes associated with OS were subsequently tested in MPM cell lines.

RESULTS: High levels of mRNA encoding DNA polymerase delta 1, catalytic subunit (POLD1) were significantly associated with reduced OS in patients with MPM (p<0.001, Log-rank test). In addition, siRNA targeting POLD1 (siPOLD1) caused cell cycle arrest at the G1/S checkpoint and induced apoptosis involving accumulation of DNA damage in MPM cell lines.

CONCLUSION: POLD1 plays essential roles in overcoming DNA damage and cell cycle progression at the G1/S checkpoint in MPM cells. These findings suggest that POLD1 may be a novel therapeutic target in MPM.}, } @article {pmid38413635, year = {2024}, author = {Elkahwagy, DM and Kiriacos, CJ and Sobeih, ME and Khorshid, OMR and Mansour, M}, title = {The lncRNAs Gas5, MALAT1 and SNHG8 as diagnostic biomarkers for epithelial malignant pleural mesothelioma in Egyptian patients.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {4823}, pmid = {38413635}, issn = {2045-2322}, mesh = {Humans ; Biomarkers ; Biomarkers, Tumor/genetics ; Egypt ; *Mesothelioma/diagnosis/genetics ; *Mesothelioma, Malignant ; *RNA, Long Noncoding/genetics ; }, abstract = {Long noncoding RNAs have been shown to be involved in a myriad of physiological and pathological pathways. To date, malignant pleural mesothelioma (MPM) is considered an extremely aggressive cancer. One reason for this is the late diagnosis of the disease, which can occur within 30-40 years of asbestos exposure. There is an immense need for the development of new, sensitive, inexpensive and easy methods for the early detection of this disease other than invasive methods such as biopsy. The aim of this study was to determine the expression of circulating lncRNAs in mesothelioma patient plasma to identify potential biomarkers. Ten previously identified lncRNAs that were shown to be aberrantly expressed in mesothelioma tissues were selected as candidates for subsequent validation. The expression of the ten selected candidate lncRNAs was verified via quantitative PCR (qPCR) in human plasma samples from mesothelioma patients versus healthy controls. The expression levels of circulating GAS5, SNHG8 and MALAT1 were significantly greater in plasma samples from patients than in those from controls. The ROC analysis of both MALAT1 and SNHG8 revealed 88.89% sensitivity and 66.67% specificity. The sensitivity of these markers was greater than that of GAS5 (sensitivity 72.22% and specificity 66.67%). The regression model for GAS5 was statistically significant, while that for SNHG8 and MALAT1 was not significant due to the small sample size. The area under the curve (AUC) of the three ROC curves was acceptable and significant: 0.7519 for GAS5, 0.7352 for SNHG8 and 0.7185 for MALAT1. This finding confirmed their ability to be used as markers. The three lncRNAs were not affected by age, sex or smoking status. The three lncRNAs showed great potential as independent predictive diagnostic biomarkers. Although the prediction model for MALAT1 did not significantly differ, MALAT1 was significantly expressed in patients more than in controls (p = 0.0266), and the recorded sensitivity and specificity were greater than those of GAS5.}, } @article {pmid38412661, year = {2024}, author = {Kalla, C and Ott, G and Finotello, F and Niewola-Staszkowska, K and Conza, GD and Lahn, M and van der Veen, L and Schüler, J and Falkenstern-Ge, R and Kopecka, J and Riganti, C}, title = {The highly selective and oral phosphoinositide 3-kinase delta (PI3K-δ) inhibitor roginolisib induces apoptosis in mesothelioma cells and increases immune effector cell composition.}, journal = {Translational oncology}, volume = {43}, number = {}, pages = {101857}, pmid = {38412661}, issn = {1936-5233}, abstract = {Targeting aberrantly expressed kinases in malignant pleural mesothelioma (MPM) is a promising therapeutic strategy. We here investigated the effect of the novel and highly selective Phosphoinositide 3-kinase delta (PI3K-δ) inhibitor roginolisib (IOA-244) on MPM cells and on the immune cells in MPM microenvironment. To this aim, we analyzed the expression of PI3K-δ by immunohistochemistry in specimens from primary MPM, cell viability and death in three different MPM cell lines treated with roginolisib alone and in combination with ipatasertib (AKT inhibitor) and sapanisertib (mTOR inhibitor). In a co-culture model of patient-derived MPM cells, autologous peripheral blood mononuclear cells and fibroblasts, the tumor cell viability and changes in immune cell composition were investigated after treatment of roginolisib with nivolumab and cisplatin. PI3K-δ was detected in 66/89 (74%) MPM tumors and was associated with reduced overall survival (12 vs. 25 months, P=0.0452). Roginolisib induced apoptosis in MPM cells and enhanced the anti-tumor efficacy of AKT and mTOR kinase inhibitors by suppressing PI3K-δ/AKT/mTOR and ERK1/2 signaling. Furthermore, the combination of roginolisib with chemotherapy and immunotherapy re-balanced the immune cell composition, increasing effector T-cells and reducing immune suppressive cells. Overall, roginolisib induces apoptosis in MPM cells and increases the antitumor immune cell effector function when combined with nivolumab and cisplatin. These results provide first insights on the potential of roginolisib as a therapeutic agent in patients with MPM and its potential in combination with established immunotherapy regimen.}, } @article {pmid38410609, year = {2024}, author = {Congedo, MT and West, EC and Evangelista, J and Mattingly, AA and Calabrese, G and Sassorossi, C and Nocera, A and Chiappetta, M and Flamini, S and Abenavoli, L and Margaritora, S and Boccuto, L and Lococo, F}, title = {The genetic susceptibility in the development of malignant pleural mesothelioma: somatic and germline variants, clinicopathological features and implication in practical medical/surgical care: a narrative review.}, journal = {Journal of thoracic disease}, volume = {16}, number = {1}, pages = {671-687}, pmid = {38410609}, issn = {2072-1439}, abstract = {BACKGROUND AND OBJECTIVE: Malignant pleural mesothelioma (MPM) is a very aggressive primary tumor of the pleura whose main risk factor is exposure to asbestos. However, only a minority of exposed people develops MPM and the incidence of MPM cases without an apparent association with asbestos exposure has been increasing in recent years, suggesting that genetic predisposing factors may play a crucial role. In addition, several studies reported familial cases of MPM, suggesting that heredity may be an important and underestimated feature in MPM development. Several candidate genes have been associated with a predisposition to MPM and most of them play a role in DNA repair mechanisms: overall, approximately 20% of MPM cases may be related to genetic predisposition. A particular category of patients with high susceptibility to MPM is represented by carriers of pathogenic variants in the BAP1 gene. Germline variants in BAP1 predispose to the development of MPM following an autosomal dominant pattern of inheritance in the familial cases. MPMs in these patients are significantly less aggressive, and patients require a multidisciplinary approach that involves genetic counseling, medical genetics, pathology, surgical, medical, and radiation oncology expertise. In the present narrative review, we presented a comprehensive overview of genetic susceptibility in the development of MPM.

METHODS: The narrative review is based on a selective literature carried out in PubMed in 2023. Inclusion criteria were original articles in English language, and clinical trials (randomized, prospective, or retrospective).

KEY CONTENT AND FINDINGS: We summarized the somatic and germline variants and the differences in terms of clinicopathological features and prognosis between gene-related MPM (GR-MPM) and asbestos-related MPM (AR-MPM). We also discussed the indications for screening, genetic testing, and surveillance of patients with BAP1 germline variants.

CONCLUSIONS: In this narrative review, we have emphasized that the BAP1 gene's harmful germline variations are inherited in an autosomal dominant manner in familial cases. MPMs in individuals with these variations are less severe, and their medical care necessitates a collaborative effort. Additionally, we have outlined the current therapeutic prospects for MPM, including the possibility of gene-specific therapy, which is currently promising but still requires clinical validation.}, } @article {pmid38409016, year = {2024}, author = {Nazar, T and Gopalakrishnabhaktan, A and Tashrifwala, FAA and Sathish, A and Dave, T}, title = {Testicular mesothelioma disguised as hydrocele: a case report.}, journal = {Journal of medical case reports}, volume = {18}, number = {1}, pages = {114}, pmid = {38409016}, issn = {1752-1947}, mesh = {Male ; Humans ; Middle Aged ; *Mesothelioma, Malignant/complications ; *Mesothelioma/diagnostic imaging/surgery ; *Testicular Hydrocele/diagnosis/surgery/etiology ; *Testicular Neoplasms/diagnosis/surgery/complications ; }, abstract = {BACKGROUND: Testicular tumors have many different manifestations. The majority of these cases are presented as an incidental finding during hydrocelectomy. Malignant mesotheliomas are uncommon tumours that can arise from the coelomic epithelium of the pleura, peritoneum, pericardium, and tunica vaginalis.

CASE PRESENTATION: We present a 51-year-old South Asian (Indian) male patient with a rare case of mesothelioma, presenting with right hydrocele, to whom a right hydrocelectomy was performed. Any history of trauma or asbestos exposure was not present. Histopathological and immunohistochemistry reports revealed a malignant mesothelioma of tunica vaginalis. There was no invasion of the tumour to the epididymis and spermatic cord. Imaging studies showed no signs of metastasis. 1 month later, a high inguinal orchidectomy was performed. The patient underwent adjuvant chemotherapy thereafter and is still on follow-up.

CONCLUSION: Although hydrocele is common, detailed evaluation is mandatory to rule out certain rare tumours-testicular and paratesticular variants.}, } @article {pmid38406142, year = {2024}, author = {Qasim, A and Allu, SVV and Schmidt, P and Parikh, HR and Moore, S and Yapor, L and Soliman, M}, title = {Comprehensive Review of Mesothelioma Cases: From Diagnosis to Therapeutic Strategies.}, journal = {Cureus}, volume = {16}, number = {1}, pages = {e52859}, pmid = {38406142}, issn = {2168-8184}, abstract = {Mesothelioma is a rare and aggressive malignancy typically associated with asbestos exposure. We present the clinical and diagnostic journey of a 63-year-old male carpenter, who presented with concerning symptoms of shortness of breath and total right lung "white-out" on imaging. Comprehensive medical evaluation revealed the presence of malignant pleural mesothelioma. This study underscores the importance of considering mesothelioma as a potential diagnosis in individuals with occupational asbestos exposure and highlights patterns in diagnosing and managing this devastating disease. Early recognition and intervention are essential in improving outcomes for patients diagnosed with mesothelioma.}, } @article {pmid38404135, year = {2024}, author = {Barnes, H and Hoy, RF}, title = {Changing trends in mesothelioma: Important lessons for an occupational disease registry.}, journal = {Respirology (Carlton, Vic.)}, volume = {29}, number = {4}, pages = {269-270}, doi = {10.1111/resp.14692}, pmid = {38404135}, issn = {1440-1843}, mesh = {Humans ; *Mesothelioma/epidemiology/etiology ; *Mesothelioma, Malignant ; *Occupational Diseases/epidemiology ; Registries ; *Occupational Exposure/adverse effects ; *Asbestos/adverse effects ; *Pleural Neoplasms ; }, } @article {pmid38402124, year = {2024}, author = {Mukhopadhyay, D and Cocco, P and Orrù, S and Cherchi, R and De Matteis, S}, title = {The role of MicroRNAs as early biomarkers of asbestos-related lung cancer: A systematic review and meta-analysis.}, journal = {Pulmonology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.pulmoe.2024.02.002}, pmid = {38402124}, issn = {2531-0437}, abstract = {BACKGROUND: Asbestos is still the leading cause of occupational cancer mortality worldwide. Asbestos-related lung cancer (LC) and malignant pleural mesothelioma (MPM) prognosis is still poor especially at advanced stage, so early diagnosis biomarkers are needed. MicroRNAs (miRNAs) have been proposed as potential early diagnostic biomarkers of asbestos-related LC and MPM.

AIM: To evaluate the role of miRNAs as diagnostic and prognostic biomarkers of asbestos-related LC and MPM by performing a literature systematic review and meta-analysis.

METHODS: MEDLINE, EMBASE via Ovid, PUBMED and Cochrane library databases were systematically searched up to April 2023 to identify relevant articles. A grey literature search was also conducted using the Google Scholar platform. MeSH and free text terms for 'asbestos', 'occupational exposure', 'lung cancer', 'mesothelioma' and 'miRNAs' were used to search the literature. Our systematic review protocol was registered in the PROSPERO database. Study quality was assessed via the Newcastle-Ottawa Scale.

RESULTS: From the search, 331 articles were retrieved, and, after applying our selection criteria, and exclusion of one study for poor quality, 27 studies were included in the review. Most of the studies were hospital-based case-control, conducted in Europe, and evaluated MPM among men only. MiRNAs expression was measured mainly in plasma or serum. MiR-126, miR-132-3p, and miR-103a-3p were the most promising diagnostic biomarkers for MPM, and we estimated a pooled area under the curve (AUC) of 85 %, 73 %, and 50 %, respectively. In relation to MPM prognosis, miR-197‑3p resulted associated with increased survival time. MiR-126, alone and combined with miR-222, was confirmed associated also to LC diagnosis, together with miR-1254 and miR-574-5p; no miRNA was found associated to LC prognosis.

CONCLUSION: Based on our systematic literature review there is suggestive evidence that the expression of specific miRNAs in the blood serum or plasma are associated with asbestos-related LC and MPM diagnosis and prognosis. Further large longitudinal studies are urgently needed to validate these findings and elucidate the underlying mechanisms given the potential important implications for patients' survival.}, } @article {pmid38397189, year = {2024}, author = {Oliveto, S and Ritter, P and Deroma, G and Miluzio, A and Cordiglieri, C and Benvenuti, MR and Mutti, L and Raimondi, MT and Biffo, S}, title = {The Impact of 3D Nichoids and Matrix Stiffness on Primary Malignant Mesothelioma Cells.}, journal = {Genes}, volume = {15}, number = {2}, pages = {}, pmid = {38397189}, issn = {2073-4425}, support = {PRIN2020//PRIN/ ; WCR2022//WCR/ ; }, mesh = {Humans ; *Mesothelioma, Malignant ; *Mesothelioma/genetics/metabolism/pathology ; Collagen ; Cell Movement/genetics ; }, abstract = {Malignant mesothelioma is a type of cancer that affects the mesothelium. It is an aggressive and deadly form of cancer that is often caused by exposure to asbestos. At the molecular level, it is characterized by a low number of genetic mutations and high heterogeneity among patients. In this work, we analyzed the plasticity of gene expression of primary mesothelial cancer cells by comparing their properties on 2D versus 3D surfaces. First, we derived from primary human samples four independent primary cancer cells. Then, we used Nichoids, which are micro-engineered 3D substrates, as three-dimensional structures. Nichoids limit the dimension of adhering cells during expansion by counteracting cell migration between adjacent units of a substrate with their microarchitecture. Tumor cells grow effectively on Nichoids, where they show enhanced proliferation. We performed RNAseq analyses on all the samples and compared the gene expression pattern of Nichoid-grown tumor cells to that of cells grown in a 2D culture. The PCA analysis showed that 3D samples were more transcriptionally similar compared to the 2D ones. The 3D Nichoids induced a transcriptional remodeling that affected mainly genes involved in extracellular matrix assembly. Among these genes responsible for collagen formation, COL1A1 and COL5A1 exhibited elevated expression, suggesting changes in matrix stiffness. Overall, our data show that primary mesothelioma cells can be effectively expanded in Nichoids and that 3D growth affects the cells' tensegrity or the mechanical stability of their structure.}, } @article {pmid38396947, year = {2024}, author = {Okado, S and Kato, T and Hanamatsu, Y and Emoto, R and Imamura, Y and Watanabe, H and Kawasumi, Y and Kadomatsu, Y and Ueno, H and Nakamura, S and Mizuno, T and Takeuchi, T and Matsui, S and Chen-Yoshikawa, TF}, title = {CHST4 Gene as a Potential Predictor of Clinical Outcome in Malignant Pleural Mesothelioma.}, journal = {International journal of molecular sciences}, volume = {25}, number = {4}, pages = {}, pmid = {38396947}, issn = {1422-0067}, mesh = {Humans ; *Asbestos/toxicity ; Biomarkers, Tumor/genetics/metabolism ; *Mesothelioma, Malignant/diagnosis/genetics ; Survival Analysis ; }, abstract = {Malignant pleural mesothelioma (MPM) develops primarily from asbestos exposures and has a poor prognosis. In this study, The Cancer Genome Atlas was used to perform a comprehensive survival analysis, which identified the CHST4 gene as a potential predictor of favorable overall survival for patients with MPM. An enrichment analysis of favorable prognostic genes, including CHST4, showed immune-related ontological terms, whereas an analysis of unfavorable prognostic genes indicated cell-cycle-related terms. CHST4 mRNA expression in MPM was significantly correlated with Bindea immune-gene signatures. To validate the relationship between CHST4 expression and prognosis, we performed an immunohistochemical analysis of CHST4 protein expression in 23 surgical specimens from surgically treated patients with MPM who achieved macroscopic complete resection. The score calculated from the proportion and intensity staining was used to compare the intensity of CHST4 gene expression, which showed that CHST4 expression was stronger in patients with a better postoperative prognosis. The median overall postoperative survival was 107.8 months in the high-expression-score group and 38.0 months in the low-score group (p = 0.044, log-rank test). Survival after recurrence was also significantly improved by CHST4 expression. These results suggest that CHST4 is useful as a prognostic biomarker in MPM.}, } @article {pmid38384604, year = {2024}, author = {Bairos Menezes, M and Pedroso de Lima, R and Dunões, I and Inácio, M and Dinis, R}, title = {A Complete Response to Pembrolizumab in Malignant Peritoneal Mesothelioma: A Case Report.}, journal = {Cureus}, volume = {16}, number = {1}, pages = {e52716}, pmid = {38384604}, issn = {2168-8184}, abstract = {Malignant peritoneal mesothelioma (MPeM) is a rare cancer of the peritoneum with a poor prognosis and nonspecific clinical course. We discuss a case of MPeM in a 59-year-old male who presented with abdominal pain and distension, without any known previous asbestos exposure. The diagnosis was made after a second biopsy finally confirmed epithelioid MPeM in an advanced stage with pleural effusion. The patient underwent six cycles of chemotherapy with cisplatin and pemetrexed, experienced disease progression, and was then started on pembrolizumab as a second-line treatment. The patient achieved a complete response after two years of treatment with pembrolizumab and has been disease-free for almost four years with an Eastern Cooperative Oncology Group (ECOG) performance status of 0. Despite the lack of evidence to support the treatment with immunotherapy for MPeM, our case report encourages its use, highlighting its ability to enable a complete response with pembrolizumab with an excellent quality of life.}, } @article {pmid38378028, year = {2024}, author = {Mervic, A and Goricar, K and Blagus, T and Franko, A and Trebusak-Podkrajsek, K and Fikfak, MD and Dolzan, V and Kovac, V}, title = {Telomere length and TERT polymorphisms as biomarkers in asbestos-related diseases.}, journal = {Radiology and oncology}, volume = {58}, number = {1}, pages = {87-98}, pmid = {38378028}, issn = {1581-3207}, mesh = {Humans ; *Telomerase/genetics ; Case-Control Studies ; Retrospective Studies ; Polymorphism, Single Nucleotide ; Biomarkers ; Telomere/genetics ; Disease Progression ; }, abstract = {BACKGROUND: Asbestos exposure has been proposed as a risk factor for shorter telomere length. The aim of our study was to investigate whether telomere length in leukocytes and hTERT genetic polymorphisms may serve as potential biomarkers for the risk of developing asbestos-related diseases and as biomarkers of progression and chemotherapy response rate in malignant mesothelioma (MM).

SUBJECTS AND METHODS: We conducted two retrospective studies. In the first study, a case-control study, telomere length and hTERT polymorphisms were determined in patients with MM, subjects with pleural plaques and controls without the asbestos related disease, who were occupationally exposed to asbestos. In the second study, a longitudinal observational study, telomere length was also determined in samples from MM patients before and after chemotherapy. Telomere length was determined by monochromatic multiplex quantitative polymerase chain reaction (PCR), while competitive allele-specific PCR was used to genotype hTERT rs10069690, rs2736100 and rs2736098. Logistic regression and survival analysis were used in statistical analysis.

RESULTS: Patients with MM had shorter telomere length than subjects with pleural plaques (p < 0.001). After adjustment for age, rs2736098 CT, and rs10069690 TT and CT+TT genotypes were significantly associated with a higher risk of MM (padj = 0.023; padj = 0.026 and padj = 0.017), while rs2736100 AA and CA+AA genotypes conferred to a lower risk for MM compared to all other subjects (padj = 0.017, and padj = 0.026). Telomere length was not associated with a response to chemotherapy (p > 0.05) or time to disease progression (p > 0.05). Carriers of one or two polymorphic rs10069690 T alleles had a good response to chemotherapy (p = 0.039, and p = 0.048), these associations remained statistically significant after adjustment for age (padj = 0.019; padj = 0.017). Carriers of two polymorphic rs2736100 A alleles had a longer time to disease progression (p = 0.038).

CONCLUSIONS: Shorter telomere length and hTERT polymorphisms may serve as a biomarker for the risk of developing MM. Additionally, rs10069690 and rs2736100 polymorphisms, but not telomere length, were associated with a chemotherapy response or MM progression.}, } @article {pmid38377382, year = {2024}, author = {Tian, T and Xie, H and Huang, M}, title = {Epithelial Malignant Pleural Mesothelioma Mimics Lymphoma on 18 F-FDG PET/MRI : A Case Report.}, journal = {Clinical nuclear medicine}, volume = {49}, number = {4}, pages = {359-360}, doi = {10.1097/RLU.0000000000005095}, pmid = {38377382}, issn = {1536-0229}, mesh = {Male ; Humans ; Middle Aged ; *Mesothelioma, Malignant ; Fluorodeoxyglucose F18 ; *Lymphoma ; *Mesothelioma/diagnostic imaging ; Magnetic Resonance Imaging ; Positron-Emission Tomography ; }, abstract = {Malignant pleural mesothelioma is a rare tumor with a poor prognosis. We describe a case of 55-year-old man without asbestos exposure history presenting with extensive lymph nodes with high 18 F-FDG uptake in PET/MRI but atypical pleural manifestations thereby being misdiagnosed for lymphoma. Pathological examination concludes for an epithelioid mesothelioma-associated lymph node metastasis. This case emphasizes that with the extensive lymph node abnormalities shown in PET imaging, in addition to the general consideration of lymphoma, it is still necessary to be vigilant about the possibility of mesothelioma and emphasizes the necessity of pathological examination.}, } @article {pmid38350880, year = {2024}, author = {Tilsed, CM and Morales, MLO and Zemek, RM and Gordon, BA and Piggott, MJ and Nowak, AK and Fisher, SA and Lake, RA and Lesterhuis, WJ}, title = {Tretinoin improves the anti-cancer response to cyclophosphamide, in a model-selective manner.}, journal = {BMC cancer}, volume = {24}, number = {1}, pages = {203}, pmid = {38350880}, issn = {1471-2407}, mesh = {Humans ; Animals ; Mice ; *Tretinoin/pharmacology/therapeutic use ; Cyclophosphamide ; CD8-Positive T-Lymphocytes ; Combined Modality Therapy ; *Mesothelioma/drug therapy ; Tumor Microenvironment ; }, abstract = {BACKGROUND: Chemotherapy is included in treatment regimens for many solid cancers, but when administered as a single agent it is rarely curative. The addition of immune checkpoint therapy to standard chemotherapy regimens has improved response rates and increased survival in some cancers. However, most patients do not respond to treatment and immune checkpoint therapy can cause severe side effects. Therefore, there is a need for alternative immunomodulatory drugs that enhance chemotherapy.

METHODS: We used gene expression data from cyclophosphamide (CY) responders and non-responders to identify existing clinically approved drugs that could phenocopy a chemosensitive tumor microenvironment (TME), and tested combination treatments in multiple murine cancer models.

RESULTS: The vitamin A derivative tretinoin was the top predicted upstream regulator of response to CY. Tretinoin pre-treatment induced an inflammatory, interferon-associated TME, with increased infiltration of CD8 + T cells, sensitizing the tumor to subsequent chemotherapy. However, while combination treatment significantly improved survival and cure rate in a CD4[+] and CD8[+] T cell dependent manner in AB1-HA murine mesothelioma, this effect was model-selective, and could not be replicated using other cell lines.

CONCLUSIONS: Despite the promising data in one model, the inability to validate the efficacy of combination treatment in multiple cancer models deprioritizes tretinoin/cyclophosphamide combination therapy for clinical translation.}, } @article {pmid38341199, year = {2024}, author = {Mizuhashi, K and Okamoto, K and Nabeshima, K and Kishimoto, T}, title = {Detailed clinical course of a patient with rapidly progressing sarcomatoid pleural mesothelioma without p16 deletion with systemic haematogenous metastasis to soft tissues.}, journal = {BMJ case reports}, volume = {17}, number = {2}, pages = {}, pmid = {38341199}, issn = {1757-790X}, mesh = {Humans ; Male ; *Asbestos ; Disease Progression ; *Lung Neoplasms/pathology ; *Mesothelioma/diagnosis/genetics/pathology ; *Mesothelioma, Malignant ; *Pleural Effusion ; *Pleural Neoplasms/pathology ; Aged, 80 and over ; }, abstract = {Sarcomatoid mesothelioma is difficult to differentiate from other mesotheliomas. Here, we describe the case of a man in his early 80s with sarcomatoid mesothelioma and a history of asbestos exposure. He initially presented with right-sided chest pain and was examined. Right-sided pleural effusion was detected; therefore, he was hospitalised. Based on the observed pleural effusion and biopsy result, the presence of a malignant tumour was excluded; hence, he was diagnosed with benign asbestos pleurisy. He subsequently developed left-sided pleural effusion, masses and lung nodules, and died 9.5 months after the initial examination. A definitive diagnosis of sarcomatoid mesothelioma with rapid systemic progression was established after detailed investigations using autopsy specimens. This rare case of mesothelioma-without p16 deletion (detected using fluorescence in situ hybridisation)-presented differently from the usual sarcomatoid mesothelioma.}, } @article {pmid38341059, year = {2024}, author = {Xiong, X and Zhang, S and Liao, X and Du, J and Zheng, W and Hu, S and Wei, Q and Yang, L}, title = {An umbrella review of the evidence associating occupational carcinogens and cancer risk at 19 anatomical sites.}, journal = {Environmental pollution (Barking, Essex : 1987)}, volume = {345}, number = {}, pages = {123531}, doi = {10.1016/j.envpol.2024.123531}, pmid = {38341059}, issn = {1873-6424}, mesh = {Humans ; *Mesothelioma ; *Lung Neoplasms/chemically induced/epidemiology ; *Asbestos ; Carcinogens/toxicity ; *Occupational Exposure/adverse effects ; Formaldehyde/*adverse effects ; *Respiratory Hypersensitivity ; }, abstract = {Occupational exposure to carcinogens of increasing cancer risk have been extensively suggested. A robust assessment of these evidence is needed to guide public policy and health care. We aimed to classify the strength of evidence for associations of 13 occupational carcinogens (OCs) and risk of cancers. We searched PubMed and Web of Science up to November 2022 to identify potentially relevant studies. We graded the evidence into convincing, highly suggestive, suggestive, weak, or not significant according to a standardized classification based on: random-effects p value, number of cancer cases, 95% confidence interval of largest study, heterogeneity between studies, 95% prediction interval, small study effect, excess significance bias and sensitivity analyses with credibility ceilings. The quality of meta-analysis was evaluated by AMSTAR 2. Forty-eight articles yielded 79 meta-analyses were included in current umbrella review. Evidence of associations were convincing (class I) or highly suggeastive (class II) for asbestos exposure and increasing risk of lung cancer among smokers (RR = 8.79, 95%CI: 5.81-13.25 for cohort studies and OR = 8.68, 95%CI: 5.68-13.24 for case-control studies), asbestos exposure and increasing risk of mesothelioma (RR = 4.61, 95%CI: 2.57-8.26), and formaldehyde exposure and increasing risk of sinonasal cancer (RR = 1.68, 95%CI: 1.38-2.05). Fifteen associations were supported by suggestive evidence (class III). In summary, the current umbrella review found strong associations between: asbestos exposure and increasing risk of lung cancer among smokers; asbestos exposure and increasing risk of mesothelioma; and formaldehyde exposure and higher risk of sinonasal cancer. Other associations might be genuine, but substantial uncertainty remains.}, } @article {pmid38323897, year = {2024}, author = {Järvholm, B and Burdorf, A}, title = {Asbestos and disease - a public health success story?.}, journal = {Scandinavian journal of work, environment & health}, volume = {50}, number = {2}, pages = {53-60}, pmid = {38323897}, issn = {1795-990X}, mesh = {Humans ; Public Health ; *Asbestos/adverse effects ; *Occupational Exposure/adverse effects/analysis ; *Neoplasms ; *Occupational Health ; *Mesothelioma/epidemiology ; *Lung Neoplasms/epidemiology ; *Asbestosis/epidemiology ; }, abstract = {OBJECTIVE: This paper discusses the failure and success of society to decrease the adverse health effects of asbestos exposure on workers' health in relation to scientific knowledge.

METHODS: The findings are based on a narrative literature review.

RESULTS: Early warnings of the adverse health effects of workplace exposure to asbestos were published already in the 1930s. Serious health effects, such as malignancies and fibrosis due to occupational asbestos exposure, were highlighted in major medical journals and textbooks in late 1960s. New technologies could detect also asbestos fibers in the lung of non-occupational exposed persons in the 1970s. The first bans for using asbestos came in the early 1970s, and more general bans by authorities came in the 1980s and continue until today.

CONCLUSIONS: The rather late recognition of adverse effects of asbestos exposure in the general population and measures to decrease the exposure through more general bans came rather late. However, the very strong measures such as general bans in many countries have been a success. A Swedish study showed that the general ban and other measures have decreased the risk of malignancies due to occupational exposure. The effect of the bans on adverse effects in the general population has yet to be studied. Analysis of fibers in the lungs of persons born after the bans could be an efficient method.}, } @article {pmid38318560, year = {2024}, author = {Subahi, EA and Fadul, A and Mohamed, A and Alsayed, A and Ali, EA and Sayed, S and Mustafa, S and Wazwaz, B and Fadul, MH}, title = {Biphasic Peritoneal Mesothelioma Is a Rare Tumor and a Diagnostic Challenge: A Case Report.}, journal = {Cureus}, volume = {16}, number = {1}, pages = {e51725}, pmid = {38318560}, issn = {2168-8184}, abstract = {Malignant peritoneal mesothelioma (MPM) is a rare subtype of mesothelioma. There are three main histological subtypes of mesothelioma: epithelioid, sarcomatoid, and biphasic (mixed). Risk factors include asbestos exposure, previous radiation, and some germline mutations. Treatment includes surgical resection of amenable tumors or cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. We present a 34-year-old male who presented with weight loss, night sweats, and pleuritic chest pain and was found to have ascites with peritoneal nodularity on abdominal imaging. He had a history of tuberculosis contact, but no history of asbestos exposure. After a long challenging and interesting diagnostic process, he was subsequently diagnosed with biphasic MPM. The diagnostic challenge stems from not only the rarity of the tumor but also from the absence of risk factors, the unavailability of some special laboratory investigations, in addition to the potentially misleading effect of tuberculosis exposure history, a top differential diagnosis in the case. This is a case report of a really challenging and totally unexpected diagnosis of biphasic peritoneal mesothelioma in a patient with tuberculosis exposure, constitutional symptoms, but no history of asbestos exposure. It highlights the diagnostic process as well as the importance of early diagnosis to improve the overall survival of such malignancies.}, } @article {pmid38301599, year = {2024}, author = {Fitzgerald, SM}, title = {Resolving asbestos and ultrafine particulate definitions with carcinogenicity.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {189}, number = {}, pages = {107478}, doi = {10.1016/j.lungcan.2024.107478}, pmid = {38301599}, issn = {1872-8332}, mesh = {Humans ; *Lung Neoplasms ; *Asbestos ; Minerals ; *Calcinosis ; }, abstract = {As asbestos fibers and other fine particles have been studied extensively to correlate physical and chemical properties with their potential for negative human health impact on inhalation, there remains no concise definitions for the individual particle types nor collective considerations of combined variabilities. Extensive studies relating negative health to asbestos morphology, chemistry, surface effects, and biodurability form general qualitative bins of what is more likely causative or less, but do not provide enough information to quantitatively dismiss particles with parameters outside any given range. Further, natural mineral species and accessory mineralization makes standardization of universally applicable reference materials nearly unobtainable. With modern advent of engineered nanoparticles, we are adding even more unknowns to the universe of the microscopic size fraction and its potential for human disease, and our paradigm is challenged.}, } @article {pmid38297314, year = {2024}, author = {Reamon-Buettner, SM and Rittinghausen, S and Klauke, A and Hiemisch, A and Ziemann, C}, title = {Malignant peritoneal mesotheliomas of rats induced by multiwalled carbon nanotubes and amosite asbestos: transcriptome and epigenetic profiles.}, journal = {Particle and fibre toxicology}, volume = {21}, number = {1}, pages = {3}, pmid = {38297314}, issn = {1743-8977}, support = {BMBF-No. 03X0109A//BMBF-funded CarboTox "Development of screening methods to analyze the carcinogenic potentials of carbon nanotubes/ ; BMBF-No. 03X0109A//BMBF-funded CarboTox "Development of screening methods to analyze the carcinogenic potentials of carbon nanotubes/ ; BMBF-No. 03X0109A//BMBF-funded CarboTox "Development of screening methods to analyze the carcinogenic potentials of carbon nanotubes/ ; BMBF-No. 03X0109A//BMBF-funded CarboTox "Development of screening methods to analyze the carcinogenic potentials of carbon nanotubes/ ; BMBF-No. 03X0109A//BMBF-funded CarboTox "Development of screening methods to analyze the carcinogenic potentials of carbon nanotubes/ ; Nos. 507334 and 50781//Fraunhofer-ITEM-funded pilot research "MWCNT-Mesothelioma"/ ; Nos. 507334 and 50781//Fraunhofer-ITEM-funded pilot research "MWCNT-Mesothelioma"/ ; Nos. 507334 and 50781//Fraunhofer-ITEM-funded pilot research "MWCNT-Mesothelioma"/ ; Nos. 507334 and 50781//Fraunhofer-ITEM-funded pilot research "MWCNT-Mesothelioma"/ ; Nos. 507334 and 50781//Fraunhofer-ITEM-funded pilot research "MWCNT-Mesothelioma"/ ; }, mesh = {Humans ; Rats ; Animals ; *Mesothelioma, Malignant/complications/genetics ; Asbestos, Amosite/toxicity ; *Nanotubes, Carbon/toxicity ; *Mesothelioma/chemically induced/genetics ; Transcriptome ; Rats, Wistar ; *Asbestos/toxicity ; Carcinogenesis/chemically induced/genetics ; DNA Methylation ; Epigenesis, Genetic ; *Lung Neoplasms/chemically induced/genetics/pathology ; GADD45 Proteins ; Antigens, Differentiation/toxicity ; }, abstract = {BACKGROUND: Malignant mesothelioma is an aggressive cancer that often originates in the pleural and peritoneal mesothelium. Exposure to asbestos is a frequent cause. However, studies in rodents have shown that certain multiwalled carbon nanotubes (MWCNTs) can also induce malignant mesothelioma. The exact mechanisms are still unclear. To gain further insights into molecular pathways leading to carcinogenesis, we analyzed tumors in Wistar rats induced by intraperitoneal application of MWCNTs and amosite asbestos. Using transcriptomic and epigenetic approaches, we compared the tumors by inducer (MWCNTs or amosite asbestos) or by tumor type (sarcomatoid, epithelioid, or biphasic).

RESULTS: Genome-wide transcriptome datasets, whether grouped by inducer or tumor type, showed a high number of significant differentially expressed genes (DEGs) relative to control peritoneal tissues. Bioinformatic evaluations using Ingenuity Pathway Analysis (IPA) revealed that while the transcriptome datasets shared commonalities, they also showed differences in DEGs, regulated canonical pathways, and affected molecular functions. In all datasets, among highly- scoring predicted canonical pathways were Phagosome Formation, IL8 Signaling, Integrin Signaling, RAC Signaling, and TREM1 Signaling. Top-scoring activated molecular functions included cell movement, invasion of cells, migration of cells, cell transformation, and metastasis. Notably, we found many genes associated with malignant mesothelioma in humans, which showed similar expression changes in the rat tumor transcriptome datasets. Furthermore, RT-qPCR revealed downregulation of Hrasls, Nr4a1, Fgfr4, and Ret or upregulation of Rnd3 and Gadd45b in all or most of the 36 tumors analyzed. Bisulfite sequencing of Hrasls, Nr4a1, Fgfr4, and Ret revealed heterogeneity in DNA methylation of promoter regions. However, higher methylation percentages were observed in some tumors compared to control tissues. Lastly, global 5mC DNA, m6A RNA and 5mC RNA methylation levels were also higher in tumors than in control tissues.

CONCLUSIONS: Our findings may help better understand how exposure to MWCNTs can lead to carcinogenesis. This information is valuable for risk assessment and in the development of safe-by-design strategies.}, } @article {pmid38292909, year = {2024}, author = {Tagarakis, G and Tsolaki, F and Tagarakis, I}, title = {Commentary: The role of single nucleotide polymorphisms related to iron homeostasis in mesothelioma susceptibility after asbestos exposure: a genetic study on autoptic samples.}, journal = {Frontiers in public health}, volume = {12}, number = {}, pages = {1336545}, pmid = {38292909}, issn = {2296-2565}, mesh = {Humans ; Polymorphism, Single Nucleotide ; *Mesothelioma/genetics ; *Mesothelioma, Malignant ; *Asbestos/adverse effects ; Iron ; Homeostasis ; }, } @article {pmid38292377, year = {2023}, author = {Fazzo, L and Grande, E and Zona, A and Minelli, G and Crialesi, R and Iavarone, I and Grippo, F}, title = {Mortality rates from asbestos-related diseases in Italy during the first year of the COVID-19 pandemic.}, journal = {Frontiers in public health}, volume = {11}, number = {}, pages = {1243261}, pmid = {38292377}, issn = {2296-2565}, mesh = {Adult ; Humans ; Female ; Male ; Aged, 80 and over ; *Mesothelioma, Malignant ; *Asbestosis/epidemiology/etiology ; *Mesothelioma/epidemiology/etiology ; Pandemics ; *Lung Neoplasms ; *COVID-19/epidemiology/complications ; SARS-CoV-2 ; *Asbestos/adverse effects ; Italy/epidemiology ; }, abstract = {BACKGROUND AND AIM: Patients with interstitial lung diseases, including asbestosis, showed high susceptibility to the SARS-CoV-2 virus and a high risk of severe COVID-19 symptoms. Italy, highly impacted by asbestos-related diseases, in 2020 was among the European countries with the highest number of COVID-19 cases. The mortality related to malignant mesotheliomas and asbestosis in 2020 and its relationship with COVID-19 in Italy are investigated.

METHODS: All death certificates involving malignant mesotheliomas or asbestosis in 2010-2020 and those involving COVID-19 in 2020 were retrieved from the National Registry of Causes of Death. Annual mortality rates and rate ratios (RRs) of 2020 and 2010-2014 compared to 2015-2019 were calculated. The association between malignant pleural mesothelioma (MPM) and asbestosis with COVID-19 in deceased adults ≥80 years old was evaluated through a logistic regression analysis (odds ratios: ORs), using MPM and asbestosis deaths COVID-19-free as the reference group. The hospitalization for asbestosis in 2010-2020, based on National Hospital Discharge Database, was analyzed.

RESULTS: In 2020, 746,343 people died; out of them, 1,348 involved MPM and 286 involved asbestosis. Compared to the period 2015-2019, the mortality involving the two diseases decreased in age groups below 80 years; meanwhile, an increasing trend was observed in subjects aged 80 years and older, with a relative mortality risks of 1.10 for MPM and 1.17 for asbestosis. In subjects aged ≥80 years, deaths with COVID-19 were less likely to have MPM in both genders (men: OR = 0.22; women: OR = 0.44), while no departure was observed for asbestosis. A decrease in hospitalization in 2020 with respect to those in 2010-2019 in all age groups, both considering asbestosis as the primary or secondary diagnosis, was observed.

CONCLUSIONS: The increasing mortality involving asbestosis and, even if of slight entity, MPM, observed in people aged over 80 years during the 1[st] year of the COVID-19 pandemic, aligned in part with the previous temporal trend, could be due to several factors. Although no positive association with COVID-19 mortality was observed, the decrease in hospitalizations for asbestosis among individuals aged over 80 years, coupled with the increase in deaths, highlights the importance of enhancing home-based assistance during the pandemic periods for vulnerable patients with asbestos-related conditions.}, } @article {pmid38250976, year = {2023}, author = {Kang, MS and Chae, WR and Lee, YJ and Moon, KW}, title = {Occupational and Environmental Asbestos Exposure and Survival of Patients with Asbestos-Related Cancer: A Follow-Up Study on Patients with Malignant Mesothelioma and Asbestos-Related Lung Cancer in Korea.}, journal = {Toxics}, volume = {12}, number = {1}, pages = {}, pmid = {38250976}, issn = {2305-6304}, abstract = {Malignant mesothelioma and asbestos-related lung cancer are typically associated with a poor prognosis. However, it has been observed that some patients with these cancers survive significantly longer than the average survival period. While many preliminary studies have investigated factors influencing patient survival, the specific impact of asbestos exposure has not been thoroughly explored. We followed up with 546 patients with malignant mesothelioma and 902 patients with asbestos-related lung cancer, all identified as asbestos victims between 2009 and 2021. In both malignant mesothelioma and asbestos-related lung cancer, patients with occupational asbestos exposure exhibited not only shorter median survival times but also lower 3- and 5-year survival rates compared to those with environmental exposure. Additionally, a longer duration of occupational exposure and closer proximity to the source of asbestos were linked to shorter survival times and lower survival rates. Among the patients with occupational asbestos exposure, the highest hazard ratios (HRs) were observed in those who worked in the production of asbestos-containing products across both cancer types. In contrast, significant HRs were only noted in mesothelioma patients who lived near asbestos industries, slate houses, and redevelopment areas, within the environmentally exposed group.}, } @article {pmid38249898, year = {2023}, author = {Visonà, SD and Capella, S and Borrelli, P and Villani, S and Favaron, C and Kurzhunbaeva, Z and Colosio, C and Belluso, E}, title = {Asbestos burden in lungs of non-occupationally exposed women from Broni (Pavia, Italy): a postmortem SEM-EDS study.}, journal = {Journal of thoracic disease}, volume = {15}, number = {12}, pages = {6555-6569}, pmid = {38249898}, issn = {2072-1439}, abstract = {BACKGROUND: In Italy the incidence of malignant mesothelioma (MM) among women is remarkably high, due to the several contexts in which women had been exposed to asbestos. However, very few studies in literature focus on the inorganic lung content in women. The aim of this retrospective, observational study is to investigate the asbestos lung burden, in terms of concentration, dimensions and type of asbestos, in 42 women who died from MM and had been non-occupationally exposed to asbestos during the activity of the asbestos-cement plant located in Broni (Pavia, Northern Italy) where mainly chrysotile, crocidolite and amosite were used.

METHODS: Lung samples taken during forensic autopsies have been digested using sodium hypochlorite and filtered through a cellulose-ester membrane. The filter was examined using a scanning electron microscope and the chemical composition of the fibers was analyzed using an electron dispersive spectroscopy. The number of detected inorganic fibers, asbestos fibers and asbestos bodies (ABs) were normalized to 1 gram of dry tissue.

RESULTS: In six samples no asbestos has been detected. Overall, the most represented kind of asbestos was amosite, followed by crocidolite, tremolite/actinolite asbestos and chrysotile. The concentration of all inorganic fibers was significantly higher in women with environmental and household exposures compared with those with only environmental exposure (P=0.025), as well as the concentration of asbestos fibers (P=0.019) and ABs (P=0.049). We found a significant correlation between the concentration of asbestos fibers and the duration of exposure (rho =0.413, P=0.008), as well as with the latency of MM (rho =0.427, P=0.005). The distance of the residential address from the factory and the time spent daily in contact with asbestos did not influence the lung asbestos burden.

CONCLUSIONS: These results suggest the relevance of the lung clearance of asbestos, regarding mainly chrysotile. As a consequence, although scanning electron microscopy -energy dispersive X-ray spectroscopy (SEM-EDS) is considered the most reliable tool for assessing previous exposure to asbestos, its results should be interpreted with caution, especially in a legal context. In addition, our data confirm the relevance of environmental and household exposure in determining asbestos concentration in lungs and highlight the importance of household exposure.}, } @article {pmid38247448, year = {2024}, author = {Schüz, J and Kovalevskiy, E and Olsson, A and Moissonnier, M and Ostroumova, E and Ferro, G and Feletto, E and Schonfeld, SJ and Byrnes, G and Tskhomariia, I and Straif, K and Morozova, T and Kromhout, H and Bukhtiyarov, I}, title = {Cancer mortality in chrysotile miners and millers, Russian Federation: main results (Asbest Chrysotile Cohort-Study).}, journal = {Journal of the National Cancer Institute}, volume = {116}, number = {6}, pages = {866-875}, pmid = {38247448}, issn = {1460-2105}, support = {001/WHO_/World Health Organization/International ; /NH/NIH HHS/United States ; //Ministry of Health of the Russian Federation/ ; 2009-2014//National System of Chemical and Biological Safety of the Russian Federation/ ; //Federal State Budgetary Scientific Institution/ ; //Izmerov Research Institute of Occupational Health/ ; //International Agency for Research on Cancer/ ; 2015-2023/WHO_/World Health Organization/International ; /CA/NCI NIH HHS/United States ; /NH/NIH HHS/United States ; }, mesh = {Humans ; Male ; *Asbestos, Serpentine/adverse effects ; Female ; *Occupational Exposure/adverse effects ; *Lung Neoplasms/mortality/epidemiology ; Middle Aged ; Russia/epidemiology ; Cohort Studies ; *Occupational Diseases/mortality/epidemiology ; Adult ; Dust ; Aged ; Miners/statistics & numerical data ; Mining/statistics & numerical data ; }, abstract = {BACKGROUND: We investigated mortality in workers of the world's largest chrysotile mine and enrichment factories located in the town of Asbest, Russian Federation.

METHODS: This historical cohort study included all workers employed for at least 1 year between 1975 and 2010 and follow-up until the end of 2015. Cumulative exposure to dust was estimated based on workers' complete occupational history linked to dust measurements systematically collected from the 1950s. Exposure to chrysotile fibers was estimated using dust-to-fiber conversion factors. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated as mortality rate ratios in Poisson regression models.

RESULTS: A total of 30 445 (32% women) workers accumulated 721 312 person-years at risk and 11 110 (36%) died. Of the workers, 54% had more than 30 years since their first exposure. We found an exposure-response between cumulative dust and lung cancer mortality in men. No clear association with dust exposure but a modest increase in the highest category of fiber exposure was seen for lung cancer in women. Mesothelioma mortality was increased (RR = 7.64, 95% CI = 1.18 to 49.5, to at least 80 fibers per cm3 years and RR = 4.56, 95% CI = 0.94 to 22.1, to at least 150 mg/m3 years [dust]), based on 13 deaths. For colorectal and stomach cancer, there were inconsistent associations. No associations were seen for laryngeal or ovarian cancer.

CONCLUSION: In this large-scale epidemiological study in the world's largest active asbestos mine, we confirmed an increased risk of mesothelioma with high fiber exposure and an increasing mortality for lung cancer in men with increasing dust exposure. Less clear-cut increased lung cancer mortality was seen in the women. Continued mortality follow-up is warranted.}, } @article {pmid38239857, year = {2024}, author = {Behers, BM and Guske, CW and Behers, BJ and Kortum, SB and Bermingham, IG and Warner, CL and Carey, RI}, title = {Malignant Epithelioid Mesothelioma of the Tunica Vaginalis Testis Presenting as Hydrocele in a Kidney Transplant Recipient.}, journal = {Case reports in urology}, volume = {2024}, number = {}, pages = {9227764}, pmid = {38239857}, issn = {2090-696X}, abstract = {Mesotheliomas of the tunica vaginalis testis are rare malignant tumors that can present as a scrotal mass or hydrocele. These tumors are typically aggressive with high rates of recurrence and metastasis. Suspected risk factors for malignant mesothelioma include asbestos exposure, chronic inflammation, trauma, and persistent hydrocele. We report the case of a malignant epithelioid mesothelioma of the tunica vaginalis testis that presented as a finding at hydrocelectomy and was ultimately treated with radical inguinal orchiectomy. This patient was on chronic immunosuppression therapy with tacrolimus and mycophenolate mofetil secondary to a kidney transplant but had none of the common risk factors for mesothelioma formation. To our knowledge, this is the first case describing a possible connection between chronic immunosuppression and mesothelioma of the tunica vaginalis. However, future studies are needed to investigate this association and discern whether this could have played a role in our patient or if his mesothelioma formation was coincidental.}, } @article {pmid38201520, year = {2023}, author = {Iser, S and Hintermair, S and Varga, A and Çelik, A and Sayan, M and Kankoç, A and Akyürek, N and Öğüt, B and Bertoglio, P and Capozzi, E and Solli, P and Ventura, L and Waller, D and Weber, M and Stubenberger, E and Ghanim, B}, title = {Validation of Inflammatory Prognostic Biomarkers in Pleural Mesothelioma.}, journal = {Cancers}, volume = {16}, number = {1}, pages = {}, pmid = {38201520}, issn = {2072-6694}, support = {ATU 67837709//Karl Landsteiner University of Health Sciences/ ; }, abstract = {Evoked from asbestos-induced inflammation, pleural mesothelioma represents a fatal diagnosis. Therapy ranges from nihilism to aggressive multimodality regimens. However, it is still unclear who ultimately benefits from which treatment. We aimed to re-challenge inflammatory-related biomarkers' prognostic value in times of modern immune-oncology and lung-sparing surgery. The biomarkers (leukocytes, hemoglobin, platelets, neutrophils, lymphocytes, monocytes, neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), platelet-lymphocyte ratio (PLR), C-reactive protein (CRP)) and clinical characteristics (age, sex, histology, therapy) of 98 PM patients were correlated to overall survival (OS). The median OS was 19.4 months. Significant OS advantages (Log-Rank) were observed in multimodal treatment vs. others (26.1 vs. 7.2 months, p < 0.001), surgery (pleurectomy/decortication) vs. no surgery (25.5 vs. 3.8 months, p < 0.001), a high hemoglobin level (cut-off 12 g/dL, 15 vs. 24.2 months, p = 0.021), a low platelet count (cut-off 280 G/L, 26.1 vs. 11.7 months, p < 0.001), and a low PLR (cut-off 194.5, 25.5 vs. 12.3 months, p = 0.023). Histology (epithelioid vs. non-epithelioid, p = 0.002), surgery (p = 0.004), CRP (cut-off 1 mg/dL, p = 0.039), and platelets (p = 0.025) were identified as independent prognostic variables for this cohort in multivariate analysis (Cox regression, covariates: age, sex, histology, stage, CRP, platelets). Our data verified the previously shown prognostic role of systemic inflammatory parameters in patients treated with lung-sparing surgery within multimodality therapy.}, } @article {pmid38192052, year = {2024}, author = {Carney, JM and Sporn, TA and Roggli, VL and Pavlisko, EN}, title = {The diagnosis of asbestosis in the 21[st] century: a clinicopathological correlation of 102 cases.}, journal = {Ultrastructural pathology}, volume = {48}, number = {2}, pages = {137-148}, doi = {10.1080/01913123.2023.2299874}, pmid = {38192052}, issn = {1521-0758}, mesh = {Male ; Humans ; Female ; Middle Aged ; Aged ; Aged, 80 and over ; *Asbestosis/pathology ; *Asbestos ; Lung/pathology ; *Mesothelioma/complications/pathology ; Asbestos, Amosite ; *Lung Neoplasms/pathology ; *Mesothelioma, Malignant ; *Occupational Exposure ; }, abstract = {Asbestosis, defined as diffuse pulmonary fibrosis caused by inhalation of asbestos fibers, occurs after heavy exposures to asbestos dust over several decades. Because workplace exposures have been significantly curtailed since the banning of asbestos in insulation products, we were interested in examining the clinicopathological characteristics of cases diagnosed in the 21[st] century. The consultation files of one of the authors (VLR) were reviewed for cases of asbestosis diagnosed since 1/1/2001. 102 cases were identified, with a median age of 75 years (range: 45-89). There were 100 men and 2 women. The women were from Turkey and Brazil (none from the United States). Malignancies were present in 78 cases, including 38 lung cancers, 29 pleural mesotheliomas, and 8 peritoneal mesotheliomas. The grade of asbestosis was available in 88 cases (median severity of 2; scale: 1-4). Pleural plaque was present in 94% of cases. The most common exposure categories were insulators (39), shipyard workers (16), asbestos manufacturing (9), boiler workers (8) and pipefitter/welders (6). The median duration of exposure was 33 years (range: 2-49 years). Lung fiber burden analysis was performed in 34 cases, with amosite being the predominant fiber type. Results were compared with similar information for 475 cases diagnosed prior to 1/1/2001.}, } @article {pmid38190277, year = {2024}, author = {Hung, YP and Chirieac, LR}, title = {Molecular and Immunohistochemical Testing in Mesothelioma and Other Mesothelial Lesions.}, journal = {Archives of pathology & laboratory medicine}, volume = {148}, number = {5}, pages = {e77-e89}, doi = {10.5858/arpa.2023-0213-RA}, pmid = {38190277}, issn = {1543-2165}, mesh = {Humans ; *Mesothelioma/diagnosis/genetics/metabolism/pathology ; *Immunohistochemistry ; *Biomarkers, Tumor/genetics/metabolism/analysis ; Neoplasms, Mesothelial/diagnosis/genetics/metabolism/pathology ; Mesothelioma, Malignant/diagnosis/genetics/pathology/metabolism ; Mutation ; *Tumor Suppressor Proteins ; *Ubiquitin Thiolesterase ; }, abstract = {CONTEXT.—: Molecular testing has increasingly been utilized in the evaluation of mesothelioma. Diffuse mesothelioma comprises multiple distinct genetic subgroups. While most diffuse mesotheliomas lack oncogenic kinase mutations and instead harbor alterations involving tumor suppressors and chromatin regulators, a minor subset of tumors is characterized by uncommon alterations such as germline mutations, genomic near-haploidization, ALK rearrangement, ATF1 rearrangement, or EWSR1::YY1 fusion.

OBJECTIVE.—: To provide updates on the salient molecular features of diffuse mesothelioma, mesothelioma in situ, and other mesothelial lesions: well-differentiated papillary mesothelial tumor, adenomatoid tumor, peritoneal inclusion cyst, and others. We consider the diagnostic, prognostic, and predictive utility of molecular testing in mesothelial lesions.

DATA SOURCES.—: We performed a literature review of recently described genetic features, molecular approaches, and immunohistochemical tools, including BAP1, MTAP, and merlin in mesothelioma and other mesothelial lesions.

CONCLUSIONS.—: Our evolving understanding of the molecular diversity of diffuse mesothelioma and other mesothelial lesions has led to considerable changes in pathology diagnostic practice, including the application of immunohistochemical markers such as BAP1, MTAP, and merlin (NF2), which are surrogates of mutation status. In young patients and/or those without significant asbestos exposure, unusual mesothelioma genetics such as germline mutations, ALK rearrangement, and ATF1 rearrangement should be considered.}, } @article {pmid38182448, year = {2024}, author = {Carney, JM and Roggli, VL and Glass, CH and Piña-Oviedo, S and Pavlisko, EN}, title = {The over diagnosis of diffuse mesothelioma: An analysis of 311 cases with recommendations for the avoidance of pitfalls.}, journal = {Annals of diagnostic pathology}, volume = {68}, number = {}, pages = {152248}, doi = {10.1016/j.anndiagpath.2023.152248}, pmid = {38182448}, issn = {1532-8198}, mesh = {Humans ; Overdiagnosis ; *Pleural Neoplasms/diagnosis/metabolism/pathology ; Biomarkers, Tumor/analysis ; *Mesothelioma/diagnosis/pathology ; *Mesothelioma, Malignant/diagnosis ; *Carcinoma/pathology ; *Lung Neoplasms/diagnosis/pathology ; Diagnosis, Differential ; }, abstract = {BACKGROUND: The diagnosis of mesothelioma may be challenging. We investigated a large database of cases in order to determine the frequency with which a diagnosis of mesothelioma was made incorrectly and the most frequent causes of error.

DESIGN: A database including more than 4000 consultation cases of histologically confirmed mesothelioma was examined to identify cases in which mesothelioma was diagnosed by at least one pathologist when the available information pointed towards a different diagnosis.

RESULTS: There were 311 cases misdiagnosed as mesothelioma. The most common category was metastatic carcinoma to the pleura or peritoneum (129 cases: 73 lung carcinomas, 15 renal cell carcinomas). The next most common category was primary lung cancer (111 cases: 55 sarcomatoid carcinoma, 56 pseudomesotheliomatous carcinoma). The third most common category was primary malignancies arising from or near the serosal membranes (33 cases). The fourth most common category was fibrous pleurisy (38 cases). The most common errors were failure to consider important radiographic information regarding the gross distribution of tumor, lack of awareness or consideration of another malignancy, overreliance on certain immunohistochemical results, and failure to perform certain diagnostic histochemical, immunohistochemical, or ultrastructural studies.

CONCLUSIONS: There are a number of diagnostic pitfalls that can lead to the over diagnosis of mesothelioma. Careful attention to clinical and radiographic information as well as performance of appropriate ancillary tests can help to prevent such misdiagnoses. Detailed examples will be presented to assist in the avoidance of these pitfalls with emphasis on the most commonly observed errors.}, } @article {pmid38176439, year = {2024}, author = {van der Linde, LIS and Hantzsch-Kuhn, B and Ellebrecht, D and Stellmacher, F and Welker, L}, title = {[Interdisciplinary diagnostics and therapy of malignant mesothelioma].}, journal = {Pneumologie (Stuttgart, Germany)}, volume = {78}, number = {4}, pages = {262-268}, doi = {10.1055/a-2202-5445}, pmid = {38176439}, issn = {1438-8790}, mesh = {Humans ; *Mesothelioma, Malignant ; *Mesothelioma/therapy/drug therapy ; *Pleural Neoplasms/diagnosis/therapy/pathology ; Prognosis ; Combined Modality Therapy ; }, abstract = {The asbestos-related malignant mesothelioma (MM) is one of the common occupational cancers in Germany with approximately 1000 new cases per year. Provided that the appropriate diagnostic criteria are fulfilled, MM can be diagnosed with high specificity from both histological and cytological specimens. However, many MM are detected cyto-/histologically only at advanced stages. Clinical/radiological aspects complement each other and enable interdisciplinary assessment of tumor stage and individualized decisions on the best possible therapeutic options. Diagnostically, video-assisted thoracoscopy (VATS) has the highest priority. Therapy planning is based on the MM subtype, tumor spread and stage, and the patient's clinical condition. MM has generally a very unfavorable prognosis. Accordingly, the standard therapy aims at a macroscopic radical tumor resection in terms of cytoreduction within the framework of a suitable multimodal therapy concept (chemotherapy, radiotherapy, psychooncology). The aim of palliative measures should be primarily symptom control. Overall, interdisciplinary diagnosis and therapy of MM is crucial for the best possible care of MM patients.}, } @article {pmid38166430, year = {2024}, author = {Shaker, N and Blankenship, H and Shaker, N and Ben Musa, R and Niu, S and Alrohaibani, A and Mansoor, I and Abu Shakra, R and Sangueza, OP}, title = {Malignant Para-Testicular Mesothelioma: A Rare Presentation in the Tunica Vaginalis of an Elderly Male With No Prior Asbestos Exposure.}, journal = {International journal of surgical pathology}, volume = {32}, number = {6}, pages = {1117-1122}, doi = {10.1177/10668969231215426}, pmid = {38166430}, issn = {1940-2465}, mesh = {Humans ; Male ; Aged ; *Testicular Neoplasms/pathology/diagnosis ; *Mesothelioma, Malignant/pathology/diagnosis ; *Biomarkers, Tumor/analysis/metabolism ; Diagnosis, Differential ; Mesothelioma/diagnosis/pathology ; Testis/pathology ; Lung Neoplasms/diagnosis/pathology ; }, abstract = {Malignant mesothelioma of the tunica vaginalis is an extremely rare and aggressive tumor that is frequently encountered in elderly patients. The diagnosis of malignant mesothelioma of the tunica vaginalis poses a diagnostic challenge due to its infrequency and nonspecific clinical presentation. Histopathological examination and immunohistochemical staining are essential in differentiating this tumor from other para-testicular masses and establishing a definitive diagnosis. Early detection and comprehensive treatment planning are crucial for improving the prognosis and overall outcomes for patients with this rare malignancy. We present a report of malignant mesothelioma of the tunica vaginalis in a 78-year-old male patient with no history of asbestos exposure who presented with a large infiltrative left para-testicular mass. Histopathological examination revealed a biphasic proliferation composed of epithelioid and spindle cells with infiltrative features, foci of necrosis, and increased mitotic figures. Immunohistochemical staining exhibited positive staining for WT1, D2-40, and calretinin, supporting the mesothelial origin of the tumor. Notably, BerEP4 staining was negative, arguing against carcinoma. Immunostaining for keratin 5 was positive, supporting the mesothelial differentiation. The Ki67 proliferation index was high. The differential diagnosis included adenomatoid tumors, germ cell tumors, and pleomorphic sarcoma. We aim to discuss the clinical presentation, diagnostic approach, and therapeutic approaches of this rare entity.}, } @article {pmid38153786, year = {2024}, author = {Brims, F and Kumarasamy, C and Menon, L and Olsen, N and de Klerk, N and Franklin, P}, title = {The Western Australian Mesothelioma Registry: Analysis of 60 years of cases.}, journal = {Respirology (Carlton, Vic.)}, volume = {29}, number = {4}, pages = {288-294}, doi = {10.1111/resp.14648}, pmid = {38153786}, issn = {1440-1843}, support = {1197652//National Health and Medical Research Council/ ; //Western Australia Department of Health/ ; }, mesh = {Male ; Female ; Humans ; Western Australia/epidemiology ; Australia/epidemiology ; *Mesothelioma/epidemiology ; *Mesothelioma, Malignant ; *Asbestos/adverse effects ; *Pleural Neoplasms/etiology/complications ; Registries ; Incidence ; }, abstract = {BACKGROUND AND OBJECTIVE: Australia introduced a partial ban on asbestos consumption in 1984. There is continuing concern about exposure to asbestos in the built environment and non-occupational exposures. The aim of this study was to describe epidemiological trends of mesothelioma in Western Australia (WA) over the 60 years since the first case was recorded.

METHODS: Every case of mesothelioma notified to the WA Cancer Registry is reviewed by an expert panel. Data include demographic and clinical variables including principal mode of asbestos exposure and age at first exposure. Trends over time for survival, latency and pathological subtype of mesothelioma where analysed. Incidence rates for cases exposed during home renovation where calculated.

RESULTS: Two thousand seven hundred ninety-six cases of mesothelioma were identified with males comprising the majority (n = 2368, 84.7%). The median (IQR) age at diagnosis was 70 (62-78) years, and median latency of 47 (38-55) years. Pleural mesothelioma was recorded in 2620 (93.7%) cases with the epithelioid subtype most prevalent (n = 1730, 61.9%). Overall, median survival was 298 (128-585) days and latency 46 (37-54) years, both effectively doubling over the study period. Non-occupational exposures were proportionally higher in females (52.6%), compared with males (9.5%). Home renovation was the primary exposure in 227 (8.1%) cases, with number of cases and incidence rate ratio peaking in 2005/09 but subsequently decreasing.

CONCLUSION: The annual number of cases of mesothelioma in WA may have hit a plateau. The majority of females have non-occupational exposures and incidence rates from home renovation exposure may have peaked, suggesting the ban on asbestos has been effective.}, } @article {pmid38136442, year = {2023}, author = {Weber, DG and Casjens, S and Wichert, K and Lehnert, M and Taeger, D and Rihs, HP and Brüning, T and Johnen, G and The MoMar Study Group, }, title = {Tasks and Experiences of the Prospective, Longitudinal, Multicenter MoMar (Molecular Markers) Study for the Early Detection of Mesothelioma in Individuals Formerly Exposed to Asbestos Using Liquid Biopsies.}, journal = {Cancers}, volume = {15}, number = {24}, pages = {}, pmid = {38136442}, issn = {2072-6694}, abstract = {Mesothelioma is an aggressive cancer, strongly associated with prior exposure to asbestos. Commonly, tumors are detected at late stages of the disease. Detection at early stages might be meaningful, because therapies might be more effective when the tumor burden is relatively low and the tumor has not spread to distant sites. Circulating biomarkers in blood might be a promising tool to improve the early detection of mesothelioma, but for screening in asymptomatic subjects, candidate biomarkers need to be validated in appropriate studies. This study was conducted to assess the performance of biomarkers in liquid biopsies to detect mesothelioma at early stages. Over a period of 10 years, 2769 volunteers formerly exposed to asbestos were annually examined and liquid biopsies were collected. A follow-up was completed 17 months after the last blood collection. The article provides a detailed overview of our lessons learned and experiences of conducting a prospective, longitudinal, multicenter study. The existing cohort of individuals at risk is highly suitable for the validation of blood-based biomarkers for the early detection of mesothelioma as well as lung cancer.}, } @article {pmid38136353, year = {2023}, author = {Bertin, B and Zugman, M and Schvartsman, G}, title = {The Current Treatment Landscape of Malignant Pleural Mesothelioma and Future Directions.}, journal = {Cancers}, volume = {15}, number = {24}, pages = {}, pmid = {38136353}, issn = {2072-6694}, abstract = {The incidence of malignant pleural mesothelioma is expected to increase globally. New treatment options for this malignancy are eagerly awaited to improve the survival and quality of life of patients. The present article highlights the results of recent advances in this field, analyzing data from several relevant trials. The heterogeneous tumor microenvironment and biology, together with the low mutational burden, pose a challenge for treating such tumors. So far, no single biomarker has been soundly correlated with targeted therapy development; thus, combination strategies are often required to improve outcomes. Locally applied vaccines, the expansion of genetically engineered immune cell populations such as T cells, the blockage of immune checkpoints that inhibit anti-tumorigenic responses and chemoimmunotherapy are among the most promising options expected to change the mesothelioma treatment landscape.}, } @article {pmid38136333, year = {2023}, author = {Cedres, S and Valdivia, A and Iranzo, P and Callejo, A and Pardo, N and Navarro, A and Martinez-Marti, A and Assaf-Pastrana, JD and Felip, E and Garrido, P}, title = {Current State-of-the-Art Therapy for Malignant Pleural Mesothelioma and Future Options Centered on Immunotherapy.}, journal = {Cancers}, volume = {15}, number = {24}, pages = {}, pmid = {38136333}, issn = {2072-6694}, abstract = {Malignant pleural mesothelioma (MPM) is a locally aggressive disease related to asbestos exposure with a median survival for untreated patients of 4-8 months. The combination of chemotherapy based on platinum and antifolate is the standard treatment, and the addition of bevacizumab adds two months to median survival. Recently, in first-line treatment, immunotherapy combining nivolumab with ipilimumab has been shown to be superior to chemotherapy in the CheckMate-743 study in terms of overall survival (18.1 months), leading to its approval by the FDA and EMA. The positive results of this study represent a new standard of treatment for patients with MPM; however, not all patients will benefit from immunotherapy treatment. In an effort to improve the selection of patient candidates for immunotherapy for different tumors, biomarkers that have been associated with a greater possibility of response to treatment have been described. MPM is a type of tumor with low mutational load and neo-antigens, making it a relatively non-immunogenic tumor for T cells and possibly less susceptible to responding to immunotherapy. Different retrospective studies have shown that PD-L1 expression occurs in 20-40% of patients and is associated with a poor prognosis; however, the predictive value of PD-L1 in response to immunotherapy has not been confirmed. The purpose of this work is to review the state of the art of MPM treatment in the year 2023, focusing on the efficacy results of first-line or subsequent immunotherapy studies on patients with MPM and possible chemo-immunotherapy combination strategies. Additionally, potential biomarkers of response to immunotherapy will be reviewed, such as histology, PD-L1, lymphocyte populations, and TMB.}, } @article {pmid38136262, year = {2023}, author = {Cerbone, L and Orecchia, S and Bertino, P and Delfanti, S and de Angelis, AM and Grosso, F}, title = {Clinical Next Generation Sequencing Application in Mesothelioma: Finding a Golden Needle in the Haystack.}, journal = {Cancers}, volume = {15}, number = {24}, pages = {}, pmid = {38136262}, issn = {2072-6694}, abstract = {Mesothelioma comprises a group of rare cancers arising from the mesothelium of the pleura, peritoneum, tunica vaginalis testis and pericardium. Mesothelioma is generally associated with asbestos exposure and has a dismal prognosis, with few therapeutic options. Several next generation sequencing (NGS) experiments have been performed on mesothelioma arising at different sites. These studies highlight a genomic landscape mainly characterized by a high prevalence (>20%) of genomic aberrations leading to functional losses in oncosuppressor genes such as BAP1, CDKN2A, NF2, SETD2 and TP53. Nevertheless, to date, evidence of the effect of targeting these alterations with specific drugs is lacking. Conversely, 1-2% of mesothelioma might harbor activating mutations in oncogenes with specifically approved drugs. The goal of this review is to summarize NGS applications in mesothelioma and to provide insights into target therapy of mesothelioma guided by NGS.}, } @article {pmid38134842, year = {2024}, author = {Ledda, C and Loreto, C and Lombardo, C and Cardile, V and Rapisarda, V}, title = {Mesothelin methylation, soluble mesothelin related protein levels and inflammation profiling in workers chronically exposed to naturally occurring asbestos fibers.}, journal = {Translational oncology}, volume = {40}, number = {}, pages = {101872}, pmid = {38134842}, issn = {1936-5233}, abstract = {Exposure to asbestiform fibers, including chrysotile and amphibole, is carcinogenic, causing malignant pleural mesothelioma (MPM) when inhaled. Some populations globally face Naturally Occurring Asbestos (NOA) exposure, leading to MPM cases like in Biancavilla, Italy, from Fluoro-edenite (FE) contamination. Studies show NOA exposure causes epigenetic changes, focusing on mesothelin methylation, an MPM marker, and altered inflammation, emphasizing the health risks of FE and asbestos. This research, conducted from February 2022 to October 2022, studied 125 construction workers from Biancavilla and 125 controls from 40 km away without Biancavilla work history. With at least ten years in construction and no respiratory conditions, participants underwent medical assessments and gave blood samples for analysis, including inflammation markers, mesothelin methylation, and soluble mesothelin-related protein levels. The results showed similar demographics but differing inflammation and methylation levels in exposed workers, suggesting long-term cellular changes. Pearson correlation showed intricate biomarker relationships. Significant inflammatory differences were found between FE exposed and non-exposed workers, indicating potential health impacts from FE. This raises concerns for communities like Biancavilla, emphasizing the importance of extensive epigenetic research for public health.}, } @article {pmid38126124, year = {2023}, author = {Beckett, EM and Abelmann, A and Roberts, B and Lewis, RC and Cheatham, D and Miller, EW and Hall, E and Pierce, JS}, title = {An updated evaluation of reported no-observed adverse effect levels for chrysotile, amosite, and crocidolite asbestos for lung cancer and mesothelioma.}, journal = {Critical reviews in toxicology}, volume = {53}, number = {10}, pages = {611-657}, doi = {10.1080/10408444.2023.2283169}, pmid = {38126124}, issn = {1547-6898}, mesh = {Humans ; Asbestos, Crocidolite/toxicity/analysis ; Asbestos, Serpentine/toxicity ; Asbestos, Amosite/analysis ; *Lung Neoplasms/chemically induced/epidemiology ; No-Observed-Adverse-Effect Level ; *Mesothelioma/chemically induced/epidemiology ; *Mesothelioma, Malignant/chemically induced/complications ; Asbestos, Amphibole/toxicity/analysis ; *Asbestos/toxicity/analysis ; }, abstract = {This analysis updates two previous analyses that evaluated the exposure-response relationships for lung cancer and mesothelioma in chrysotile-exposed cohorts. We reviewed recently published studies, as well as updated information from previous studies. Based on the 16 studies considered for chrysotile (<10% amphibole), we identified the "no-observed adverse effect level" (NOAEL) for lung cancer and/or mesothelioma; it should be noted that smoking or previous or concurrent occupational exposure to amphiboles (if it existed) was not controlled for. NOAEL values ranged from 2.3-<11.5 f/cc-years to 1600-3200 f/cc-years for lung cancer and from 100-<400 f/cc-years to 800-1599 f/cc-years for mesothelioma. The range of best-estimate NOAELs was estimated to be 97-175 f/cc-years for lung cancer and 250-379 f/cc-years for mesothelioma. None of the six cohorts of cement or friction product manufacturing workers exhibited an increased risk at any exposure level, while all but one of the six studies of textile workers reported an increased risk at one or more exposure levels. This is likely because friction and cement workers were exposed to much shorter chrysotile fibers. Only eight cases of peritoneal mesothelioma were reported in all studies on predominantly chrysotile-exposed cohorts combined. This analysis also proposed best-estimate amosite and crocidolite NOAELs for mesothelioma derived by the application of relative potency estimates to the best-estimate chrysotile NOAELs for mesothelioma and validated by epidemiology studies with exposure-response information. The best-estimate amosite and crocidolite NOAELs for mesothelioma were 2-5 f/cc-years and 0.6-1 f/cc-years, respectively. The rate of peritoneal mesothelioma in amosite- and crocidolite-exposed cohorts was between approximately 70- to 100-fold and several-hundred-fold higher than in chrysotile-exposed cohorts, respectively. These findings will help characterize potential worker and consumer health risks associated with historical and current chrysotile, amosite, and crocidolite exposures.}, } @article {pmid38090310, year = {2023}, author = {Liu, B and Niu, L and Lee, FF}, title = {Utilizing residential histories to assess environmental exposure and socioeconomic status over the life course among mesothelioma patients.}, journal = {Journal of thoracic disease}, volume = {15}, number = {11}, pages = {6126-6139}, pmid = {38090310}, issn = {2072-1439}, support = {R21 CA235153/CA/NCI NIH HHS/United States ; }, abstract = {BACKGROUND: Exposure misclassification based solely on the address at cancer diagnosis has been widely recognized though not commonly assessed.

METHODS: We linked 1,015 mesothelioma cases diagnosed during 2011-2015 from the New York State Cancer Registry to inpatient claims and LexisNexis administrative data and constructed residential histories. Percentile ranking of exposure to ambient air toxics and socioeconomic status (SES) were based on the National Air Toxic Assessment and United States Census data, respectively. To facilitate comparisons over time, relative exposures (REs) were calculated by dividing the percentile ranking at individual census tract by the state-level average and subtracting one. We used generalized linear regression models to compare the RE in the past with that at cancer diagnosis, adjusting for patient-level characteristics.

RESULTS: Approximately 43.7% of patients had residential information available for up to 30 years, and 96.0% up to 5 years. The median number of unique places lived was 4 [interquartile range (IQR), 2-6]. The time-weighted-average RE from all addresses available had a median of -0.11 (IQR, -0.50 to 0.30) for air toxics and -0.28 (IQR, -0.65 to 0.25) for SES. RE associated with air toxics (but not SES) was significantly higher for earlier addresses than addresses at cancer diagnosis for the 5-year [annual increase =1.24%; 95% confidence interval (CI): 0.71-1.77%; n=974] and 30-year (annual increase =0.36%; 95% CI: 0.25-0.48%; n=444) look-back windows, respectively.

CONCLUSIONS: Environmental exposure to non-asbestos air toxics among mesothelioma patients may be underestimated if based solely on the address at diagnosis. With geospatial data becoming more readily available, incorporating cancer patients' residential history would lead to reduced exposure misclassification and accurate health risk estimates.}, } @article {pmid38089107, year = {2023}, author = {Tibaduiza Torres, AL and Betancur Romero, JE and Silva Aparicio, A and Rico Mendoza, MA}, title = {[Malignant mesothelioma in Colombia: burden of disease, overview, and subnational sociodemographic index, 2015-2020Mesotelioma maligno na Colômbia: carga de morbidade, visão geral e índice sociodemográfico subnacional, entre 2015 e 2020].}, journal = {Revista panamericana de salud publica = Pan American journal of public health}, volume = {47}, number = {}, pages = {e95}, pmid = {38089107}, issn = {1680-5348}, abstract = {OBJECTIVE: Establish the disease burden of malignant mesothelioma (MM) in Colombia between 2015 and 2020, and its association with the subnational sociodemographic development index (SDI) and with asbestos sites.

METHODS: Mixed ecological study of the Colombian population diagnosed with MM (according to ICD-10) from 2015 to 2020. The global burden of disease (GBD) was estimated using the methodology proposed by Murray and Lopez, based on prevalence and mortality data obtained from official sources. The subnational (departmental level) SDI was estimated as a measure of socioeconomic development. Linear regressions were established with the GBD, SDI, and documented asbestos sites.

RESULTS: The estimated GBD of MM in Colombia during 2015-2020 was 51.71 disability-adjusted life years (DALYs) per 1 000 000 inhabitants (15 375.79 total DALYs), with predominance in people over 50 years of age (91.1%) and males (66.4%).Bogotá and Valle del Cauca were the departments with the highest number of adjusted DALYs. Bogotá had the highest SDI and Guainía and Cesar had the lowest. There was evidence of an association between DALYs and SDI, explaining 22.8% of DALYs.

CONCLUSION: Malignant mesothelioma is the cause of a large number of DALYs, predominantly in the departments with greater socioeconomic development and with companies that used to use asbestos. However, possible underdiagnosis of MM limits analysis of the information.}, } @article {pmid38076518, year = {2023}, author = {Shenouda, M and Gudmundsson, E and Li, F and Straus, CM and Kindler, HL and Dudek, AZ and Stinchcombe, T and Wang, X and Starkey, A and Armato, SG}, title = {Convolutional Neural Networks for Segmentation of Malignant Pleural Mesothelioma: Analysis of Probability Map Thresholds (CALGB 30901, Alliance).}, journal = {ArXiv}, volume = {}, number = {}, pages = {}, pmid = {38076518}, issn = {2331-8422}, support = {U10 CA180821/CA/NCI NIH HHS/United States ; U10 CA180882/CA/NCI NIH HHS/United States ; UG1 CA189863/CA/NCI NIH HHS/United States ; UG1 CA233253/CA/NCI NIH HHS/United States ; }, abstract = {Malignant pleural mesothelioma (MPM) is the most common form of malignant mesothelioma, with exposure to asbestos being the primary cause of the disease. To assess response to treatment, tumor measurements are acquired and evaluated based on a patient's longitudinal computed tomography (CT) scans. Tumor volume, however, is the more accurate metric for assessing tumor burden and response. Automated segmentation methods using deep learning can be employed to acquire volume, which otherwise is a tedious task performed manually. The deep learning-based tumor volume and contours can then be compared with a standard reference to assess the robustness of the automated segmentations. The purpose of this study was to evaluate the impact of probability map threshold on MPM tumor delineations generated using a convolutional neural network (CNN). Eighty-eight CT scans from 21 MPM patients were segmented by a VGG16/U-Net CNN. A radiologist modified the contours generated at a 0.5 probability threshold. Percent difference of tumor volume and overlap using the Dice Similarity Coefficient (DSC) were compared between the standard reference provided by the radiologist and CNN outputs for thresholds ranging from 0.001 to 0.9. CNN annotations consistently yielded smaller tumor volumes than radiologist contours. Reducing the probability threshold from 0.5 to 0.1 decreased the absolute percent volume difference, on average, from 43.96% to 24.18%. Median and mean DSC ranged from 0.58 to 0.60, with a peak at a threshold of 0.5; no distinct threshold was found for percent volume difference. The CNN exhibited deficiencies with specific disease presentations, such as severe pleural effusion or disease in the pleural fissure. No single output threshold in the CNN probability maps was optimal for both tumor volume and DSC. This study emphasized the importance of considering both figures of merit when evaluating deep learning-based tumor segmentations across probability thresholds. This work underscores the need to simultaneously assess tumor volume and spatial overlap when evaluating CNN performance. While automated segmentations may yield comparable tumor volumes to that of the reference standard, the spatial region delineated by the CNN at a specific threshold is equally important.}, } @article {pmid38072464, year = {2023}, author = {Turati, F and Rossi, M and Spinazzè, A and Pira, E and Cavallo, DM and Patel, L and Mensi, C and La Vecchia, C and Negri, E}, title = {Occupational asbestos exposure and ovarian cancer: updated systematic review.}, journal = {Occupational medicine (Oxford, England)}, volume = {73}, number = {9}, pages = {532-540}, doi = {10.1093/occmed/kqad122}, pmid = {38072464}, issn = {1471-8405}, support = {ARL_2/2018//'Fondazione Regionale per la Ricerca Biomedica'-'Bando Progetto Speciale 2017 su Patologie Amianto-Correlate'/ ; }, mesh = {Humans ; Female ; *Asbestos/adverse effects ; *Ovarian Neoplasms/etiology ; Risk ; *Occupational Exposure/adverse effects ; Time Factors ; *Mesothelioma/etiology ; *Occupational Diseases/diagnosis/etiology ; *Lung Neoplasms ; }, abstract = {BACKGROUND: The association between asbestos exposure and ovarian cancer has been questioned given the possible misdiagnosis of peritoneal mesothelioma as ovarian cancer.

AIMS: To update a systematic review on ovarian cancer risk in women occupationally exposed to asbestos, exploring the association with the time since first exposure and the duration of exposure.

METHODS: We searched PubMed from 2008 onwards, screened previous systematic reviews, combined standardized mortality ratios (SMR) using random effect models and quantified heterogeneity using the I2 statistic. To assess tumour misclassification, we compared the distribution of observed excess ovarian cancers (OEOC) to that expected (EEOC) from the distribution of peritoneal cancers in strata of latency and exposure duration.

RESULTS: Eighteen publications (20 populations), including a pooled analysis of 21 cohorts, were included. The pooled SMR was 1.79 (95% confidence interval 1.38-2.31), with moderate heterogeneity between studies (I2 = 42%), based on 144 ovarian cancer deaths/cases. The risk was increased for women with indirect indicators of higher exposure, longer duration and latency, and lower for chrysotile than for crocidolite exposure. The effect of duration and latency could not be completely disentangled, since no multivariate analysis was available for time-related variables. The dissimilarity index between OEOC and EEOC for the time since first exposure was small suggesting a similar pattern of risk.

CONCLUSIONS: While some misclassification between ovarian and peritoneal cancers cannot be excluded, the observed excess risk of ovarian cancer should be added to the overall disease burden of asbestos.}, } @article {pmid38069464, year = {2024}, author = {Visonà, SD and Bertoglio, B and Capella, S and Belluso, E and Austoni, B and Colosio, C and Kurzhunbaeva, Z and Ivic-Pavlicic, T and Taioli, E}, title = {Asbestos burden in lungs of mesothelioma patients with pleural plaques, lung fibrosis and/or ferruginous bodies at histology: a postmortem SEM-EDS study.}, journal = {Carcinogenesis}, volume = {45}, number = {3}, pages = {131-139}, doi = {10.1093/carcin/bgad090}, pmid = {38069464}, issn = {1460-2180}, mesh = {Humans ; *Pulmonary Fibrosis/complications/pathology ; *Mesothelioma, Malignant/complications/pathology ; *Asbestos/toxicity/analysis ; *Mesothelioma/chemically induced ; Lung/pathology ; *Lung Neoplasms/etiology/pathology ; *Occupational Exposure ; }, abstract = {The causal attribution of asbestos-related diseases to past asbestos exposures is of crucial importance in clinical and legal contexts. Often this evaluation is made based on the history of exposure, but this method presents important limitations. To assess past asbestos exposure, pleural plaques (PP), lung fibrosis and histological evidence of ferruginous bodies (FB) can be used in combination with anamnestic data. However, such markers have never been associated with a threshold value of inhaled asbestos. With this study we attempted to shed light on the dose-response relationship of PP, lung fibrosis and FBs, investigating if their prevalence in exposed individuals who died from malignant mesothelioma (MM) is related to the concentration of asbestos in lungs assessed using scanning electron microscopy equipped with energy dispersive spectroscopy. Moreover, we estimated the values of asbestos concentration in lungs associated with PP, lung fibrosis and FB. Lung fibrosis showed a significant positive relationship with asbestos lung content, whereas PP and FB did not. We identified, for the first time, critical lung concentrations of asbestos related to the presence of PP, lung fibrosis and FB at histology (respectively, 19 800, 26 400 and 27 400 fibers per gram of dry weight), that were all well-below the background levels of asbestos identified in our laboratory. Such data suggest that PP, lung fibrosis and FB at histology should be used with caution in the causal attribution of MM to past asbestos exposures, while evaluation of amphibole lung content using analytical electron microscopy should be preferred.}, } @article {pmid38064629, year = {2024}, author = {Yang, D and Zhou, Y and Lv, K}, title = {Analysis of Ki67 Protein Expression and Clinicopathological Features in Patients with Peritoneal Mesothelioma.}, journal = {Alternative therapies in health and medicine}, volume = {30}, number = {9}, pages = {202-209}, pmid = {38064629}, issn = {1078-6791}, mesh = {Humans ; *Ki-67 Antigen/metabolism ; *Peritoneal Neoplasms/metabolism/genetics ; *Mesothelioma/pathology/metabolism/mortality ; Male ; Female ; Prognosis ; Middle Aged ; *Biomarkers, Tumor/metabolism/genetics ; Aged ; Adult ; }, abstract = {BACKGROUND: At present, there are many treatments for peritoneal mesothelioma, but the treatment of peritoneal mesothelioma is still facing great challenges. Distant metastasis is the main cause of poor prognosis and death of patients with peritoneal mesothelioma. Ki67 is a cell proliferation marker. In recent years, it has been found to be used as a molecular marker for the diagnosis, treatment and prognosis of different tumor cells. Ki67 has been shown to play a crucial role in the occurrence and development of a variety of cancers. However, the clinical significance and biological function of Ki67 in peritoneal mesothelioma remain poorly understood.

PURPOSE: To clarify the expression of Ki67 in peritoneal mesothelioma (PC), and to explore the relationship between the expression level of Ki67 and the clinicopathological parameters and prognosis of patients with PC, and to explore the potential of Ki67 as a therapeutic target and prognostic biomarker for PC.

METHODS: TIMER database was used to compare the expression levels of Ki67 mRNA and protein in mesothelioma tissues and adjacent tissues. The relationship between the expression level of Ki67 in mesothelioma and clinicopathological characteristics, and the relationship between the expression level of Ki67 and the level of immune infiltration in mesothelioma were analyzed. The prognostic value of Ki67 in mesothelioma patients was predicted, and the overall survival curve was drawn according to the follow-up data. LinkedOmics database and GSEA were used to perform co-expression analysis and enrichment analysis of Ki67, respectively.

RESULTS: Bioinformatics analysis showed that Ki67 was highly expressed in peritoneal mesothelioma (P < .01). Immunohistochemistry showed that the positive rate of Ki67 in peritoneal mesothelioma was high, and the number of Ki67 positive cases was 62.0% (31/50 cases). Univariate analysis showed that TNM stage (P = .007), asbestos (P < .001), chemotherapy (P < .001), and Ki67 expression level (P = .029) were associated with prognosis. Multivariate analysis showed that Ki67 expression level (P = .039) and TNM stage (P = .029) were independent risk factors for the prognosis of peritoneal mesothelioma. Peritoneal mesothelioma patients with high Ki67 expression have poor OS. In addition, Ki67 is also associated with the immune infiltration of mesothelioma.

CONCLUSION: Ki67 is highly expressed in peritoneal mesothelioma. Ki67 protein plays an important role in the development of peritoneal mesothelioma and is one of the important factors to evaluate the prognosis of patients with peritoneal mesothelioma.}, } @article {pmid38063957, year = {2024}, author = {Martella, S and Aiello, MM and Bertaglia, V and Cau, R and Denaro, N and Cadoni, A and Novello, S and Scartozzi, M and Novello, G and Soto Parra, HJ and Saba, L and Solinas, C and Porcu, M}, title = {Malignant Pleural Mesothelioma: Staging and Radiological Response Criteria in Patients Treated with Immune Checkpoint Inhibitors.}, journal = {Targeted oncology}, volume = {19}, number = {1}, pages = {13-28}, pmid = {38063957}, issn = {1776-260X}, mesh = {Humans ; *Mesothelioma, Malignant/drug therapy ; Immune Checkpoint Inhibitors/therapeutic use ; Artificial Intelligence ; *Pleural Neoplasms/diagnostic imaging/drug therapy ; *Lung Neoplasms/diagnostic imaging/drug therapy ; Combined Modality Therapy ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare and challenging cancer associated with asbestos fiber exposure, which offers limited treatment options. Historically, platinum-based chemotherapy has been the primary approach, but recent developments have introduced immunotherapy as a promising alternative for the treatment of this disease. Nevertheless, the unique growth patterns and occasionally ambiguous progressive characteristics of MPM make the interpretation of radiological assessments complex. Immunotherapy further complicates matters by introducing unconventional treatment response patterns such as hyperprogression and pseudoprogression. Consequently, there is a growing imperative to integrate the standard RECIST criteria with the mesothelioma-specific mRECIST criteria (version 1.1), as outlined in iRECIST. This comprehensive review is driven by the intent to provide a valuable resource for radiologists and clinicians engaged in the diagnosis, treatment, and monitoring of MPM in the era of immunotherapy. Specifically, the current imaging methods employed for staging and follow-up will be exposed and discussed, with a focus on the technical specificities and the mRECIST 1.1 methodology. Furthermore, we will provide a discussion about major clinical trials related to the use of immunotherapy in MPM patients. Finally, the latest advancements in radiomics, the applications of artificial intelligence in MPM, and their potential impact on clinical practice for prognosis and therapy, are discussed.}, } @article {pmid38054089, year = {2023}, author = {Wang, D and Wang, YH and Chu, SC}, title = {Case Report: Early diagnosis and bevacizumab-based chemotherapy for primary pericardial mesothelioma: a case with occupational asbestos exposure history.}, journal = {Frontiers in cardiovascular medicine}, volume = {10}, number = {}, pages = {1257373}, pmid = {38054089}, issn = {2297-055X}, abstract = {BACKGROUND: Primary pericardial mesothelioma (PPM) is an exceedingly rare malignant cancer and has a poor prognosis, which has been partly attributed to its frequently delayed diagnosis due to its nonspecific syndromes, its similar presentation to benign pericardial diseases, and its non-definitive etiology. In many PPM cases, the time from presentation to definite diagnosis may last for several months or even over one year. Unlike pleural mesothelioma, the relationship between PPM and asbestos exposure remains unsettled. To date, there is no consensus on the treatment of PPM.

CASE REPORT: The patient is a 57-year-old male who had nonspecific syndromes and inconclusive image findings. The occupational long-term asbestos exposure history of this patient raised our concerns regarding potential malignancy when confronted with unexplained pericardial effusion accompanied by cardiac tamponade. The heightened suspicion prompted us to perform pericardiocentesis and biopsy on the third day after admission to our department. An early diagnosis of PPM was established by the pathological and immunohistochemical evaluation of the biopsy specimen two weeks after admission. Positron emission tomography-computed tomography revealed that the lesion was localized at the anterior part of the mediastinum without distant metastasis. This patient refused to receive cardiac surgery. He subsequently underwent six cycles of chemotherapy (cisplatin plus pemetrexed) in combination with bevacizumab (a humanized anti-VEGF antibody) as the first-line treatment, resulting in complete relief of symptoms and satisfactory outcomes with no complications. Four months after the first course, the patient initiated a second course of chemotherapy with a similar regimen, but he opted to discontinue the medical treatment after the initiation of the second course. The patient was transferred to the hospice care unit and unfortunately expired one year after the initial presentation.

CONCLUSION: We present a case of an early multidisciplinary clinical approach to diagnose and manage PPM with consideration of occupational asbestos exposure history and clinical symptoms. Bevacizumab-based chemotherapy remains an option for the treatment of PPM.}, } @article {pmid38044849, year = {2024}, author = {Klebe, S and Judge, M and Brcic, L and Dacic, S and Galateau-Salle, F and Nicholson, AG and Roggli, V and Nowak, AK and Cooper, WA}, title = {Mesothelioma in the pleura, pericardium and peritoneum: Recommendations from the International Collaboration on Cancer Reporting (ICCR).}, journal = {Histopathology}, volume = {84}, number = {4}, pages = {633-645}, doi = {10.1111/his.15106}, pmid = {38044849}, issn = {1365-2559}, mesh = {Humans ; Peritoneum ; Pleura ; Retrospective Studies ; *Mesothelioma/diagnosis ; *Mesothelioma, Malignant ; Pericardium ; *Pathology, Clinical/methods ; }, abstract = {AIMS: Mesothelioma is a rare malignancy of the serosal membranes that is commonly related to exposure to asbestos. Despite extensive research and clinical trials, prognosis to date remains poor. Consistent, comprehensive and reproducible pathology reporting form the basis of all future interventions for an individual patient, but also ensures that meaningful data are collected to identify predictive and prognostic markers.

METHODS AND RESULTS: This article details the International Collaboration on Cancer Reporting (ICCR) process and the development of the international consensus mesothelioma reporting data set. It describes the 'core' and 'non-core' elements to be included in pathology reports for mesothelioma of all sites, inclusive of clinical, macroscopic, microscopic and ancillary testing considerations. An international expert panel consisting of pathologists and a medical oncologist produced a set of data items for biopsy and resection specimens based on a critical review and discussion of current evidence, and in light of the changes in the 2021 WHO Classification of Tumours. The commentary focuses particularly upon new entities such as mesothelioma in situ and provides background on relevant and essential ancillary testing as well as implementation of the new requirement for tumour grading.

CONCLUSION: We recommend widespread and consistent implementation of this data set, which will facilitate accurate reporting and enhance the consistency of data collection, improve the comparison of epidemiological data, support retrospective research and ultimately help to improve clinical outcomes. To this end, all data sets are freely available worldwide on the ICCR website (www.iccr-cancer.org/data-sets).}, } @article {pmid38041166, year = {2023}, author = {Visonà, SD and Bertoglio, B and Favaron, C and Capella, S and Belluso, E and Colosio, C and Villani, S and Ivic-Pavlicic, T and Taioli, E}, title = {A postmortem case control study of asbestos burden in lungs of malignant mesothelioma cases.}, journal = {Journal of translational medicine}, volume = {21}, number = {1}, pages = {875}, pmid = {38041166}, issn = {1479-5876}, mesh = {Humans ; Female ; Male ; *Mesothelioma, Malignant/complications ; Asbestos, Serpentine ; Case-Control Studies ; *Mesothelioma/pathology ; *Lung Neoplasms/etiology/pathology ; *Asbestos ; Lung/pathology ; Tumor Microenvironment ; }, abstract = {BACKGROUND: Asbestos lung content is regarded as the most reliable tool for causal attribution of malignant mesothelioma (MM) to previous asbestos exposures. However, there is a lack of studies on asbestos burden in lungs of MM patients in comparison with healthy individuals. This study aims to provide such a comparison, investigating, as well, differences in asbestos lung burden with sex and time trends.

METHODS: Asbestos lung content has been assessed on formalin-fixed lung fragments using scanning electron microscopy coupled with energy dispersion spectroscopy (SEM-EDS) on individuals deceased from MM (cases) and healthy subjects without any lung disease who died from violent causes (controls) between 2005 and 2023.

RESULTS: Asbestos and asbestos bodies (ABs) were found, respectively, in 73.7% and 43.2% of cases and in 28 and 22% of controls; in MM cases the most represented asbestos types were crocidolite and amosite, whereas in controls it was tremolite-actinolite asbestos. The concentration of both asbestos fibers and ABs was statistically significantly higher in MM cases compared to controls. The mean asbestos fibers width was also significantly higher in cases than controls. Males and females with MM showed similar asbestos and ABs concentrations, but females had higher concentrations of chrysotile, and significantly lower fibers width compared to males. Time trends show that MM lung asbestos concentrations decreased starting in 2011.

DISCUSSION: The results suggest a correlation between asbestos burden in lungs and MM risk. The different concentration of chrysotile, as well as the different width of asbestos fibers in MM males and females might reflect a sex difference in response of the lung microenvironment to inhaled asbestos. Finally, this study provides the first pathological evidence of the effect of the ban of asbestos use, demonstrating a significant decrease of asbestos lung content after 2011.}, } @article {pmid38038422, year = {2023}, author = {Zupanc, C and Franko, A and Strbac, D and Kovac, V and Dolzan, V and Goricar, K}, title = {The association of genetic factors with serum calretinin levels in asbestos-related diseases.}, journal = {Radiology and oncology}, volume = {57}, number = {4}, pages = {473-486}, pmid = {38038422}, issn = {1581-3207}, mesh = {Humans ; *Asbestos/adverse effects ; *Asbestosis/genetics ; *Calbindin 2/blood ; *Mesothelioma, Malignant/genetics ; }, abstract = {BACKGROUND: Asbestos exposure is associated with different asbestos-related diseases, including malignant mesothelioma (MM). MM diagnosis is confirmed with immunohistochemical analysis of several markers, including calretinin. Increased circulating calretinin was also observed in MM. The aim of the study was to determine if CALB2 polymorphisms or polymorphisms in genes that can regulate calretinin expression are associated with serum calretinin levels or MM susceptibility.

SUBJECTS AND METHODS: The study included 288 MM patients and 616 occupationally asbestos-exposed subjects without MM (153 with asbestosis, 380 with pleural plaques and 83 without asbestos-related disease). Subjects were genotyped for seven polymorphisms in CALB2, E2F2, MIR335, NRF1 and SEPTIN7 genes using competitive allele-specific polymerase chain reaction (PCR). Serum calretinin was determined with ELISA in 545 subjects. Nonparametric tests, logistic regression and receiver operating characteristic (ROC) curve analysis were used for statistical analysis.

RESULTS: Carriers of at least one polymorphic CALB2 rs889704 allele had lower calretinin levels (P = 0.036). Carriers of two polymorphic MIR335 rs3807348 alleles had higher calretinin (P = 0.027), while carriers of at least one polymorphic NRF1 rs13241028 allele had lower calretinin levels (P = 0.034) in subjects without MM. Carriers of two polymorphic E2F2 rs2075995 alleles were less likely to develop MM (odds ratio [OR] = 0.64, 95% confidence interval [CI] = 0.43-0.96, P = 0.032), but the association was no longer significant after adjustment for age (P = 0.093). Optimal serum calretinin cut-off values differentiating MM patients from other subjects differed according to CALB2, NRF1, E2F2, and MIR335 genotypes.

CONCLUSIONS: The results of presented study suggest that genetic variability could influence serum calretinin levels. These findings could contribute to a better understanding of calretinin regulation and potentially to earlier MM diagnosis.}, } @article {pmid38036250, year = {2024}, author = {McNamee, N and Harvey, C and Gray, L and Khoo, T and Lingam, L and Zhang, B and Nindra, U and Yip, PY and Pal, A and Clay, T and Arulananda, S and Itchins, M and Pavlakis, N and Kao, S and Bowyer, S and Chin, V and Warburton, L and Pires da Silva, I and John, T and Solomon, B and Alexander, M and Nagrial, A}, title = {Brief Report: Real-World Toxicity and Survival of Combination Immunotherapy in Pleural Mesothelioma-RIOMeso.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {19}, number = {4}, pages = {636-642}, doi = {10.1016/j.jtho.2023.11.014}, pmid = {38036250}, issn = {1556-1380}, mesh = {Humans ; Male ; Aged ; Female ; Nivolumab/adverse effects ; Ipilimumab/adverse effects ; Retrospective Studies ; *Lung Neoplasms/drug therapy/etiology ; Australia ; *Mesothelioma, Malignant ; *Mesothelioma/drug therapy/etiology ; *Pleural Neoplasms/drug therapy/etiology ; Immunotherapy/adverse effects ; *Asbestos ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; }, abstract = {BACKGROUND: Australia has one of the highest rates of asbestos-associated diseases. Mesothelioma remains an area of unmet need with a 5-year overall survival of 10%. First-line immunotherapy with ipilimumab and nivolumab is now a standard of care for unresectable pleural mesothelioma following the CheckMate 743 trial, with supportive data from the later line single-arm MAPS2 trial. RIOMeso evaluates survival and toxicity of this regimen in real-world practice.

METHODS: Demographic and clinicopathologic data of Australian patients treated with ipilimumab and nivolumab in first- and subsequent-line settings for pleural mesothelioma were collected retrospectively. Survival was reported using the Kaplan-Meier method and compared between subgroups with the log-rank test. Toxicity was investigator assessed using Common Terminology Criteria for Adverse Events version 5.0.

RESULTS: A total of 119 patients were identified from 11 centers. The median age was 72 years, 83% were male, 92% had Eastern Cooperative Oncology Group less than or equal to 1, 50% were past or current smokers, and 78% had known asbestos exposure. In addition, 50% were epithelioid, 19% sarcomatoid, 14% biphasic, and 17% unavailable. Ipilimumab and nivolumab were used first line in 75% of patients. Median overall survival (mOS) was 14.5 months (95% confidence interval [CI]: 13.0-not reached [NR]) for the entire cohort. For patients treated first line, mOS was 14.5 months (95% CI: 12.5-NR) and in second- or later-line patients was 15.4 months (95% CI: 11.2-NR). There was no statistically significant difference in mOS for epithelioid patients compared with nonepithelioid (19.1 mo [95% CI: 15.4-NR] versus 13.0 mo [95% CI: 9.7-NR], respectively, p = 0.064). Furthermore, 24% of the patients had a Common Terminology Criteria for Adverse Events grade greater than or equal to 3 adverse events, including three treatment-related deaths. Colitis was the most frequent adverse event.

CONCLUSIONS: Combination immunotherapy in real-world practice has poorer survival outcomes and seems more toxic compared with clinical trial data. This is the first detailed report of real-world survival and toxicity outcomes using ipilimumab and nivolumab treatment of pleural mesothelioma.}, } @article {pmid38032359, year = {2024}, author = {Geyer, SJ}, title = {A cluster of mesotheliomas reported in a case series does not implicate chrysotile asbestos-containing friction products as the cause of mesotheliomas.}, journal = {American journal of industrial medicine}, volume = {67}, number = {1}, pages = {81-82}, doi = {10.1002/ajim.23554}, pmid = {38032359}, issn = {1097-0274}, mesh = {Humans ; Asbestos, Serpentine/toxicity ; Friction ; *Mesothelioma/chemically induced/epidemiology ; *Asbestos/toxicity ; *Lung Neoplasms/etiology ; }, } @article {pmid38030592, year = {2024}, author = {Miller, A}, title = {Recognizing the pleura in asbestos-related pleuropulmonary disease: Known and new manifestations of pleural fibrosis.}, journal = {American journal of industrial medicine}, volume = {67}, number = {1}, pages = {73-80}, doi = {10.1002/ajim.23553}, pmid = {38030592}, issn = {1097-0274}, mesh = {Humans ; *Asbestos/toxicity ; Asbestos, Amphibole/toxicity ; *Asbestosis/diagnostic imaging/pathology ; Fibrosis ; Pain ; Pleura/diagnostic imaging/pathology ; *Pleural Diseases/diagnostic imaging/etiology ; *Pleurisy/pathology ; }, abstract = {Pleural thickening (PT) is a major consequence of exposure to all fiber types of asbestos. In recent decades, it is more prevalent than parenchymal asbestosis. Its manifestations occupy a full clinical and radiographic spectrum. Six major manifestations can be identified: (a) acute pleuritis generally with effusion; (b) diffuse PT or fibrous pleuritis; (c) rounded atelectasis; (d) circumscribed PT or plaques; (e) chronic pleuritic pain; and (f) mesothelioma. Review of the experience of workers and community members in Libby, MT to asbestiform fibers in vermiculite has confirmed the appearance of these previously known benign and malignant asbestos-related diseases as well as a unique pleuropulmonary disease characterized as lamellar PT and associated with progressive decline in pulmonary function and pleuritic pain. Despite previous literature asserting that PT represents a marker for asbestos exposure without significant effect on pulmonary function and physiology, the experience of Libby amphibole (LA) disease, along with other studies, indicates that PT plays a role in declining vital capacity in those with prolonged or unusual exposures such as those arising from LA.}, } @article {pmid38017544, year = {2023}, author = {Yoshida, M and Jimbo, N and Tsukamoto, R and Itoh, T and Kawahara, K and Mitsui, S and Tanaka, Y and Maniwa, Y}, title = {Sarcomatoid mesothelioma diagnosed in a patient with mesothelioma in situ: a case report on morphologic differences after 9-month interval with details analysis of cytology in early-stage mesothelioma.}, journal = {Diagnostic pathology}, volume = {18}, number = {1}, pages = {126}, pmid = {38017544}, issn = {1746-1596}, support = {23K08317//JSPS KAKENHI/ ; 23K08317//JSPS KAKENHI/ ; }, mesh = {Male ; Humans ; Aged ; In Situ Hybridization, Fluorescence ; Homozygote ; *Lung Neoplasms/diagnosis/genetics/pathology ; Sequence Deletion ; *Mesothelioma, Malignant ; *Mesothelioma/diagnosis/genetics/pathology ; *Pleural Neoplasms/diagnosis/genetics/pathology ; *Pleural Effusion/genetics ; *Sarcoma/genetics ; Biomarkers, Tumor/genetics/analysis ; Ubiquitin Thiolesterase/analysis/genetics ; }, abstract = {BACKGROUND: Overlapping morphological features of mesothelial cells have been rendered it difficult to distinguish between reactive and malignant conditions. The development of methods based on detecting genomic abnormalities using immunohistochemistry and fluorescence in situ hybridization have contributed markedly to solving this problem. It is important to identify bland mesothelioma cells on cytological screening, perform efficient genomic-based testing, and diagnose mesothelioma, because the first clinical manifestation of pleural mesothelioma is pleural effusion, which is the first sample available for pathological diagnosis. However, certain diagnostic aspects remain challenging even for experts.

CASE PRESENTATION: This report describes a case of a 72-year-old man with a history of asbestos exposure who presented with pleural effusion as the first symptom and was eventually diagnosed as mesothelioma. Mesothelioma was suspected owing to prominent cell-in-cell engulfment in mesothelial cells on the first cytological sample, and the diagnosis of mesothelioma in situ was confirmed by histology. Unexpectedly, sarcomatoid morphology of mesothelioma was found in the second pathology samples 9 months after the first pathological examination. Both the mesothelioma in situ and invasive lesion showed immunohistochemical loss of methylthioadenosine phosphorylase (MTAP) and homozygous deletion of cyclin dependent kinase inhibitor 2A (CDKN2A) on fluorescence in situ hybridization. The patient received medication therapy but died of disease progression 12 months after the diagnosis of the sarcomatoid morphology of mesothelioma.

CONCLUSION: Our case suggests that cell-in-cell engulfment can be conspicuous in early-stage mesothelioma with inconspicuous nuclear atypia and few multinucleated cells. In addition, the presence of MTAP loss and CDKN2A homozygous deletion are suspected to be involved in early formation to invasive lesions and/or sarcomatoid morphology. We believe that it is important to consider genetic abnormalities when deciding on individual patient management. Furthermore, cases of mesothelioma, even those of an in situ lesion, with MTAP loss and/or CDKN2A deletion should be carefully followed up or subjected to early treatment.}, } @article {pmid38015374, year = {2023}, author = {Nash, A and Creaney, J}, title = {Genomic Landscape of Pleural Mesothelioma and Therapeutic Aftermaths.}, journal = {Current oncology reports}, volume = {25}, number = {12}, pages = {1515-1522}, pmid = {38015374}, issn = {1534-6269}, support = {1197652//National Health and Medical Research Council/ ; CA190450//U.S. Department of Defense/ ; }, mesh = {Humans ; *Lung Neoplasms/genetics/therapy/pathology ; *Mesothelioma, Malignant ; *Mesothelioma/genetics/therapy/pathology ; *Pleural Neoplasms/genetics/therapy/pathology ; Genomics ; Tumor Microenvironment ; }, abstract = {PURPOSE OF REVIEW: In this article, we provide a comprehensive analysis of recent progress in the genetic characterisation of pleural mesothelioma, and the translation of these findings to clinical practice.

RECENT FINDINGS: Advancements in sequencing technology have allowed the identification of driver mutations and improved our understanding of how these mutations may shape the mesothelioma tumour microenvironment. However, the identification of frequently mutated regions including CDKN2A, BAP1 and NF2 have, to date, not yet yielded targeted therapy options that outperform standard chemo- and immunotherapies. Similarly, the association between mutational profile and the immune microenvironment or immunotherapy response is not well characterised. Further research into the link between tumour mutational profile and response to therapy is critical for identifying targetable vulnerabilities and stratifying patients for therapy.}, } @article {pmid38002620, year = {2023}, author = {Sorino, C and Mondoni, M and Marchetti, G and Agati, S and Inchingolo, R and Mei, F and Flamini, S and Lococo, F and Feller-Kopman, D}, title = {Pleural Mesothelioma: Advances in Blood and Pleural Biomarkers.}, journal = {Journal of clinical medicine}, volume = {12}, number = {22}, pages = {}, pmid = {38002620}, issn = {2077-0383}, abstract = {Pleural mesothelioma (PM) is a type of cancer that is highly related to exposure to asbestos fibers. It shows aggressive behavior, and the current therapeutic approaches are usually insufficient to change the poor prognosis. Moreover, apart from staging and histological classification, there are no validated predictors of its response to treatment or its long-term outcomes. Numerous studies have investigated minimally invasive biomarkers in pleural fluid or blood to aid in earlier diagnosis and prognostic assessment of PM. The most studied marker in pleural effusion is mesothelin, which exhibits good specificity but low sensitivity, especially for non-epithelioid PM. Other biomarkers found in pleural fluid include fibulin-3, hyaluronan, microRNAs, and CYFRA-21.1, which have lower diagnostic capabilities but provide prognostic information and have potential roles as therapeutic targets. Serum is the most investigated matrix for biomarkers of PM. Several serum biomarkers in PM have been studied, with mesothelin, osteopontin, and fibulin-3 being the most often tested. A soluble mesothelin-related peptide (SMRP) is the only FDA-approved biomarker in patients with suspected mesothelioma. With different serum and pleural fluid cut-offs, it provides useful information on the diagnosis, prognosis, follow-up, and response to therapy in epithelioid PM. Panels combining different markers and proteomics technologies show promise in terms of improving clinical performance in the diagnosis and monitoring of mesothelioma patients. However, there is still no evidence that early detection can improve the treatment outcomes of PM patients.}, } @article {pmid38000500, year = {2024}, author = {Nel, AE and Pavlisko, EN and Roggli, VL}, title = {The Interplay Between the Immune System, Tumor Suppressor Genes, and Immune Senescence in Mesothelioma Development and Response to Immunotherapy.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {19}, number = {4}, pages = {551-564}, doi = {10.1016/j.jtho.2023.11.017}, pmid = {38000500}, issn = {1556-1380}, mesh = {Humans ; United States ; Aged ; Phylogeny ; *Lung Neoplasms/genetics/therapy ; *Mesothelioma/genetics/therapy ; *Mesothelioma, Malignant/genetics ; Genes, Tumor Suppressor ; *Asbestos ; Tumor Microenvironment ; }, abstract = {Despite efforts to ban asbestos mining and manufacturing, mesothelioma deaths in the United States have remained stable at approximately 2500 cases annually. This trend is not unique to the United States but is also a global phenomenon, associated with increased aging of populations worldwide. Although geoeconomic factors such as lack of regulations and continued asbestos manufacturing in resource-poor countries play a role, it is essential to consider biological factors such as immune senescence and increased genetic instability associated with aging. Recognizing that mesothelioma shares genetic instability and immune system effects with other age-related cancers is crucial because the impact of aging on mesothelioma is frequently assessed in the context of disease latency after asbestos exposure. Nevertheless, the long latency period, often cited as a reason for mesothelioma's elderly predominance, should not overshadow the shared mechanisms. This communication focuses on the role of immune surveillance in mesothelioma, particularly exploring the impact of immune escape resulting from altered TSG function during aging, contributing to the phylogenetic development of gene mutations and mesothelioma oncogenesis. The interplay between the immune system, TSGs, and aging not only shapes the immune landscape in mesothelioma but also contributes to the development of heterogeneous tumor microenvironments, significantly influencing responses to immunotherapy approaches and survival rates. By understanding the complex interplay between aging, TSG decline, and immune senescence, health care professionals can pave the way for more effective and personalized immunotherapies, ultimately offering hope for better outcomes in the fight against mesothelioma.}, } @article {pmid37995092, year = {2023}, author = {Somigliana, AB and Barbieri, PG and Cavallo, A and Colombo, R and Consonni, D and Mirabelli, D}, title = {Lung asbestos fiber burden analysis: effects of the counting rules for legal medicine evaluations.}, journal = {Inhalation toxicology}, volume = {35}, number = {11-12}, pages = {300-307}, doi = {10.1080/08958378.2023.2285789}, pmid = {37995092}, issn = {1091-7691}, mesh = {Humans ; *Asbestos/toxicity/analysis ; Lung/chemistry ; Asbestos, Amphibole/toxicity/analysis ; Asbestos, Serpentine/toxicity ; *Lung Neoplasms ; Forensic Medicine ; }, abstract = {OBJECTIVES: The work shows the effect of counting rules, such as analysis magnification and asbestos fiber dimension to be count (with length ≥5 µm or also asbestos fibers with length <5 µm) in the lung asbestos fiber burden analysis for legal medicine evaluations.

METHODS: On the same lung tissue samples, two different analyses were carried out to count any asbestos fibers with length ≥1 µm and with length ≥5 µm. Results of the amphibole burden of the two analyses were compared by linear regression analysis on log10-transformed values.

RESULTS: The analysis should be carried out at an appropriate magnification and on samples prepared in such a way as they allow the counting of very fine fibers. If the analysis is limited to the asbestos fibers with length ≥5 µm, there is a high risk of not detecting possible residual chrysotile fiber burden and thinner crocidolite asbestos fibers.

CONCLUSIONS: On average we estimated that 1 amphibole fiber with length ≥5 µm corresponds to ∼8 amphibole fibers with length ≥1 µm in the lung. The values of the Helsinki criteria should be updated taking this into account.}, } @article {pmid37977032, year = {2023}, author = {Salman, A and Abdel Mageed, SS and Fathi, D and Elrebehy, MA and Abulsoud, AI and Elshaer, SS and Khidr, EG and Al-Noshokaty, TM and Khaled, R and Rizk, NI and Elballal, MS and Sayed, GA and Abd-Elmawla, MA and El Tabaa, MM and Mohammed, OA and Ashraf, A and El-Husseiny, AA and Midan, HM and El-Dakroury, WA and Abdel-Reheim, MA and Doghish, AS}, title = {Deciphering signaling pathway interplay via miRNAs in malignant pleural mesothelioma.}, journal = {Pathology, research and practice}, volume = {252}, number = {}, pages = {154947}, doi = {10.1016/j.prp.2023.154947}, pmid = {37977032}, issn = {1618-0631}, mesh = {Humans ; *Mesothelioma, Malignant ; *MicroRNAs/genetics ; *Mesothelioma/diagnosis ; *Pleural Neoplasms/pathology ; Hedgehog Proteins ; *Lung Neoplasms/pathology ; Signal Transduction/genetics ; }, abstract = {Malignant pleural mesothelioma (MPM) is a highly invasive form of lung cancer that adversely affects the pleural and other linings of the lungs. MPM is a very aggressive tumor that often has an advanced stage at diagnosis and a bad prognosis (between 7 and 12 months). When people who have been exposed to asbestos experience pleural effusion and pain that is not explained, MPM should be suspected. After being diagnosed, most MPM patients have a one- to four-year life expectancy. The life expectancy is approximately six months without treatment. Despite the plethora of current molecular investigations, a definitive universal molecular signature has yet to be discovered as the causative factor for the pathogenesis of MPM. MicroRNAs (miRNAs) are known to play a crucial role in the regulation of gene expression at the posttranscriptional level. The association between the expression of these short, non-coding RNAs and several neoplasms, including MPM, has been observed. Although the incidence of MPM is very low, there has been a significant increase in research focused on miRNAs in the past few years. In addition, miRNAs have been found to have a role in various regulatory signaling pathways associated with MPM, such as the Notch signaling network, Wnt/β-catenin, mutation of KRAS, JAK/STAT signaling circuit, protein kinase B (AKT), and Hedgehog signaling pathway. This study provides a comprehensive overview of the existing understanding of the roles of miRNAs in the underlying mechanisms of pathogenic symptoms in MPM, highlighting their potential as viable targets for therapeutic interventions.}, } @article {pmid37975977, year = {2023}, author = {John, A and O'Sullivan, H and Popat, S}, title = {Updates in Management of Malignant Pleural Mesothelioma.}, journal = {Current treatment options in oncology}, volume = {24}, number = {12}, pages = {1758-1789}, pmid = {37975977}, issn = {1534-6277}, mesh = {Humans ; *Mesothelioma, Malignant ; *Mesothelioma/diagnosis/etiology/therapy ; Pemetrexed/therapeutic use ; *Lung Neoplasms/pathology ; *Pleural Neoplasms/diagnosis/etiology/therapy ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive asbestos-associated thoracic malignancy that is usually incurable. As demonstrated in the landmark MARS2 trial, surgical resection does not improve survival outcomes and its role in managing MPM is limited. Whilst platinum-pemetrexed chemotherapy in combination with bevacizumab was the standard first-line approach for unresectable disease, landmark phase 3 trials have now established the role of immune checkpoint inhibitors (CPIs) in the upfront management of unresectable disease: either nivolumab-ipilimumab or carboplatin-pemetrexed-pembrolizumab. Patient selection for optimal strategy remains an ongoing question. For relapsed disease novel genomic-based therapies targeting a range of aberrations including losses of the tumour suppressor genes BAP1, CDKN2A and NF2, are being evaluated. Nonetheless, the future of MPM therapeutics holds promise. Here we overview current treatment strategies in the management of MPM.}, } @article {pmid37963950, year = {2023}, author = {Gun, RT and Kendall, GM}, title = {Asbestos-related cancer in naval personnel: findings from participants in the British nuclear tests 1952-1967.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {18842}, pmid = {37963950}, issn = {2045-2322}, mesh = {Humans ; Australia/epidemiology ; *Asbestos/toxicity ; *Mesothelioma/epidemiology/etiology ; *Asbestosis/complications ; *Lung Neoplasms/epidemiology/etiology ; *Occupational Exposure/adverse effects ; *Occupational Diseases/epidemiology ; }, abstract = {Asbestos-containing materials (ACM) were present in British and Australian naval vessels throughout the twentieth century. The aim of this study was to identify and quantify the incidence of cancer in naval personnel from onboard asbestos exposure. Subjects were four cohorts of subjects who had served in the armed forces of the United Kingdom and Australia in the 1950s and 1960s. All cohorts had previously been studied, three of them in relation to radiation exposures from British nuclear testing. Comparisons of SIRs between services were made to identify cancers attributable to asbestos exposure. Excess mesotheliomas were found in naval personnel in all cohorts. In all but one cohort the lung cancer incidence was highest in navy personnel. Comparison of other smoking-related conditions indicated that the excess in navy personnel was not smoking-related. The relatively high SIRs for mesothelioma and the occurrence of deaths from asbestosis were indicative of high levels of asbestos exposure, with an expectation of cases of asbestos-related lung cancer. The findings are consistent with the occurrence of significant excesses of mesotheliomas. In addition, notwithstanding some inconsistencies in the results between the cohorts, we estimated that approximately 27% of lung cancers in Australian seamen and 12% in British seamen were related to onboard asbestos exposure.}, } @article {pmid37942251, year = {2023}, author = {Grignani, P and Visonà, SD and Fronda, MV and Borrelli, P and Monti, MC and Bertoglio, B and Conti, A and Fattorini, P and Previderè, C}, title = {The role of single nucleotide polymorphisms related to iron homeostasis in mesothelioma susceptibility after asbestos exposure: a genetic study on autoptic samples.}, journal = {Frontiers in public health}, volume = {11}, number = {}, pages = {1236558}, pmid = {37942251}, issn = {2296-2565}, mesh = {Male ; Humans ; *Mesothelioma, Malignant ; Polymorphism, Single Nucleotide ; *Occupational Exposure ; *Mesothelioma/genetics ; *Asbestos/adverse effects ; Iron/metabolism ; Homeostasis ; Tumor Microenvironment ; }, abstract = {Asbestos-related diseases still represent a major public health problem all over the world. Among them, malignant mesothelioma (MM) is a poor-prognosis cancer, arising from the serosal lining of the pleura, pericardium and peritoneum, triggered by asbestos exposure. Literature data suggest the key role of iron metabolism in the coating process leading to the formation of asbestos bodies, considered to be both protective and harmful. Two sample sets of individuals were taken into consideration, both residing in Broni or neighboring cities (Northwestern Italy) where an asbestos cement factory was active between 1932 and 1993. The present study aims to compare the frequency of six SNPs involved in iron trafficking, previously found to be related to protection/predisposition to MM after asbestos exposure, between 48 male subjects with documented asbestos exposure who died of MM and 48 male subjects who were exposed to asbestos but did not develop MM or other neoplastic respiratory diseases (Non-Mesothelioma Asbestos Exposed - NMAE). The same analysis was performed on 76 healthy male controls. The allelic and genotypic frequencies of a sub-group of 107 healthy Italian individuals contained in the 1000 genomes database were considered for comparison. PCR-multiplex amplification followed by SNaPshot mini-sequencing reaction was used. The findings presented in this study show that the allelic and genotypic frequencies for six SNP markers involved in iron metabolism/homeostasis and the modulation of tumor microenvironment are not significantly different between the two sample sets of MM and NMAE. Therefore, the SNPs here considered do not seem to be useful markers for individual susceptibility to mesothelioma. This finding is not in agreement with previous literature.}, } @article {pmid37921373, year = {2023}, author = {Esteban Porcar, A and García Gómez, M and Santana Yllobre, L and Gómez Pajares, F and Esteban Buedo, V and Usó Talamantes, R}, title = {[Reconocimiento del mesotelioma de pleura como enfermedad profesional en la Comunidad Valenciana de 2012 a 2018.].}, journal = {Revista espanola de salud publica}, volume = {97}, number = {}, pages = {}, pmid = {37921373}, issn = {2173-9110}, mesh = {Humans ; Pleura ; Retrospective Studies ; Spain/epidemiology ; *Mesothelioma/epidemiology/etiology ; *Pleural Neoplasms/etiology/complications ; *Occupational Exposure/adverse effects ; *Occupational Diseases/epidemiology/etiology ; }, abstract = {OBJECTIVE: Pleural mesothelioma is a neoplasm almost exclusively attributed to occupational exposure to asbestos and is legally considered an occupational disease. Nevertheless, only a few cases achieve that official recognition. The objective of this work was to describe and analyse this issue, and to identify the major obstacles to its recognition.

METHODS: A descriptive and retrospective epidemiological study of data was carried out, including figures and some characteristics, of all patients with pleural mesothelioma registered in the official health and labor registries of the Valencian Community from 2012 to 2018, using frequencies, proportions, and incidence rates.

RESULTS: There were large differences between the two sets of data collected in the different registries, especially regarding the number of cases. During the seven years of data examined, 590 pleural mesotheliomas were diagnosed in the Valencian public health system. Of these, the number of cases that were related to occupational exposure was at least 437. Despite the legal duty of doctors to report such cases, only 31 were reported as suspected occupational disease (7.09%), of which only 13 were ultimately officially recognized as such. It was estimated that the annual economic overcost to the public system of unrecognised patients with this occupational disease by was 2,2270,520 euros.

CONCLUSIONS: Only a small proportion of occupational mesotheliomas are officially recognized as such. This has important health care and economic repercussions for the individuals involved as well as for the public health system.}, } @article {pmid37916370, year = {2023}, author = {Aydogdu, G and Özekinci, S}, title = {Contribution of BAP1 loss and p16 (CDKN2A) deletion analysis to the definitive diagnosis of mesothelioma in effusion cytology.}, journal = {European review for medical and pharmacological sciences}, volume = {27}, number = {20}, pages = {10001-10007}, doi = {10.26355/eurrev_202310_34180}, pmid = {37916370}, issn = {2284-0729}, mesh = {Female ; Humans ; Male ; Middle Aged ; Biomarkers, Tumor/analysis ; Cyclin-Dependent Kinase Inhibitor p16/genetics ; Cyclin-Dependent Kinase Inhibitor Proteins ; Homozygote ; In Situ Hybridization, Fluorescence ; *Lung Neoplasms/genetics ; *Mesothelioma/diagnosis/genetics/metabolism ; *Mesothelioma, Malignant ; *Pleural Neoplasms ; Sequence Deletion ; Tumor Suppressor Proteins/genetics/analysis ; Ubiquitin Thiolesterase/genetics ; Adult ; Aged ; Aged, 80 and over ; }, abstract = {OBJECTIVE: The cytological diagnosis of mesothelioma is a controversial issue, and definitive diagnosis often requires ancillary tests. The aim of this study was to investigate the contribution of BRCA1-associated protein (1) (BAP1) loss and p16 (CDKN2A) homozygous deletion (HD) on the early diagnosis of mesothelioma in effusion fluids.

MATERIALS AND METHODS: Between 2019-2022, 21 pleural and peritoneal fluid samples diagnosed with atypical mesothelial proliferation in our institution were included in the study. The slides of the cases that underwent BAP1 immunohistochemistry (IHC) were retrieved from the archive and re-examined. Homozygous deletion (HD) of p16 (CDKN2A) was investigated by the fluorescence in situ hybridization (FISH) method in cell blocks of cytology samples. At least 100 atypical mesothelial cells were counted in each case, and the HD threshold value was >10%.

RESULTS: The mean age of the cases was 63.47 years (34-90 years), female/male ratio was 3/1. Of the pleural mesothelioma cases, 16 were epithelioid, 2 were biphasic, and 1 were sarcomatoid. Two cases were diagnosed with peritoneal well-differentiated papillary mesothelioma (WDPM). BAP1 loss was observed in 11 (69%) of 16 cases. HD deletion of p16 (CDKN2A) was seen in 11 (58%) patients with FISH. The HD threshold value was 10-20% in 6 of the cases, 30-50% in 3 cases, and above 90% in 2 cases. While HD deletion was observed in p16 (CDKN2A) in all biphasic and sarcomatoid cases (n=3), no deletion was observed in peritoneal WDPM (n=2). Positivity was observed with at least one method in 12 (86%) of 14 pleural mesotheliomas who underwent both BAP1 IHC and p16 (CDKN2A) FISH. Due to technical reasons, the FISH signal could not be obtained in two cell blocks, so no results could be obtained.

CONCLUSIONS: Asbestos exposure in areas where mesothelioma is endemic and/or the presence of proliferating mesothelial cells in cytological examination are important clues for diagnosis. In controversial cases, BAP1 IHC should be the first step in an ancillary test. Although the FISH method applied to cell blocks has cytology-specific limitations and difficulties, investigating the p16 (CDKN2A) deletion with FISH in selected cases will contribute to the diagnosis.}, } @article {pmid37901248, year = {2023}, author = {Qualiotto, AN and Baldavira, CM and Balancin, M and Ab'Saber, A and Takagaki, T and Capelozzi, VL}, title = {Mesothelin expression remodeled the immune-matrix tumor microenvironment predicting the risk of death in patients with malignant pleural mesothelioma.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1268927}, pmid = {37901248}, issn = {1664-3224}, mesh = {Humans ; Male ; Female ; *Mesothelioma, Malignant ; B7-H1 Antigen/metabolism ; *Mesothelioma/drug therapy ; Mesothelin ; Tumor Microenvironment ; Collagen Type I ; *Pleural Neoplasms/drug therapy ; *Lung Neoplasms/pathology ; Neoplasm Recurrence, Local ; Risk Factors ; }, abstract = {BACKGROUND: The combination of immunobiological agents with immune checkpoint proteins is a promising treatment for malignant pleural mesothelioma (MPM). Mesothelin and anti-PD-L1 antibody-drug conjugates specifically target malignant neoplastic cells, inhibit the migration and invasion of neoplastic cells, and restore the immune landscape. In this study, we confirmed the importance of mesothelin and examined the relationship between mesothelin and the immune landscape of the tumor microenvironment (TME) in two MPM cohorts.

METHODS: The discovery cohort included 82 MPM cases. Tissue microarray slides were generated, and samples were processed for hematoxylin & eosin staining, immunohistochemistry, and immunofluorescence assays. The relationship between mesothelin, biomarkers of histogenesis, histological aggressiveness, PD-L1, immune cells (CD4, CD8, CD20, CD68), and collagen type I and type V fibers was evaluated by quantitative digital analyses. The outcome was the survival time until death from disease recurrence. The exploratory cohort included 87 malignant mesothelioma (MESO) patients from The Cancer Genome Atlas database.

RESULTS: Most patients were male (70.7%) with a history of asbestos exposure (53.7%) and with the epithelioid subtype (89%). Surgical resection was performed in 85.4% of patients, and 14.6% received chemotherapy; 59.8% of patients died from disease extension to the mediastinum. Low tumor mesothelin expression was associated with tumor necrosis and nuclear grade 1, whereas high mesothelin expression was significantly associated with the epithelioid histotype and high density of T cells CD8+, macrophages CD68+, and collagen type I fibers. Cox multivariate analysis showed a high risk of death for non-operated patients [hazard ratio (HR), 3.42 (1.15-10.16)] with low tumor mesothelin levels [HR, 2.58 (1.09-6.10)] and high PD-L1 and low infiltration of T cells CD4+ [HR, 3.81 (1.58-9.18)]. In the exploratory cohort, low mesothelin and high COL1A1 and COL5A1 expression were associated with poor overall survival.

CONCLUSION: Tumor mesothelin expression associated with the TME immune landscape predicts the risk of death for patients with MPM and could be a new target for immunotherapy in MPM.}, } @article {pmid37899647, year = {2023}, author = {Yu, M and Yang, D and Chen, C and Xia, H}, title = {Effects of SETD2 on telomere length and malignant transformation property of Met-5A after one-month crocidolite exposure.}, journal = {Journal of environmental science and health. Part C, Toxicology and carcinogenesis}, volume = {41}, number = {3-4}, pages = {121-134}, doi = {10.1080/26896583.2023.2271822}, pmid = {37899647}, issn = {2689-6591}, mesh = {Humans ; *Aminobenzoates/metabolism/pharmacology ; *Asbestos, Crocidolite/toxicity/metabolism ; Cell Transformation, Neoplastic/chemically induced/metabolism/pathology ; Epithelium/metabolism/pathology ; Naphthalenes/metabolism/pharmacology ; *Histone-Lysine N-Methyltransferase/metabolism ; *Telomere Homeostasis ; }, abstract = {Crocidolite is a carcinogen contributing to the pathogenesis of malignant mesothelioma. This study aimed to characterize the possible telomere-related events mediating the malignant transformation of mesothelial cells with and without SETD2 under crocidolite exposure. The crocidolite concentration resulting in 90% viable SETD2 knockout Met-5A (Met-5A[SETD2-KO]) and Met-5A were estimated to be 0.71 μg/cm[2] and 1.8 μg/cm[2], respectively, during 72 h of exposure, which was further employed in chronical crocidolite exposure during a 72 h exposure interval per time up to 1 month. Chronical crocidolite-exposed Met-5A[SETD2-KO] (chronical Cro-Met-5A[SETD2-KO]) had higher colony formation and increased telomerase reverse transcriptase (TERT) protein levels than chronical crocidolite-exposed Met-5A (chronical Cro-Met-5A) and Met-5A[SETD2-KO]. Chronical Cro-Met-5A[SETD2-KO] had longer telomere length (TL) than chronical Cro-Met-5A, although there were no changes in TL for either chronical Cro-Met-5A or chronical Cro-Met-5A[SETD2-KO] compared with their corresponding cells without crocidolite exposure. BIBR 1532, an inhibitor targeting TERT, partially reduced colony formation and TL for chronical Cro-Met-5A[SETD2-KO], while BIBR 1532 reduced TL but had no effect on colony formation for chronical Cro-Met-5A. Therefore, SETD2 deficient mesothelial cells are susceptible to malignant transformation during chronical crocidolite exposure, and TERT-dependent TL modification likely partially drives SETD2 loss-mediated early onset of mesothelial malignant transformation.}, } @article {pmid37898984, year = {2024}, author = {May, IJ and Nowak, AK and Francis, RJ and Ebert, MA and Dhaliwal, SS}, title = {The prognostic value of F18 Fluorothymidine positron emission tomography for assessing the response of malignant pleural mesothelioma to chemotherapy - A prospective cohort study.}, journal = {Journal of medical imaging and radiation oncology}, volume = {68}, number = {1}, pages = {57-66}, doi = {10.1111/1754-9485.13592}, pmid = {37898984}, issn = {1754-9485}, support = {//National Health and Medical Research Council (NHMRC)/ ; }, mesh = {Humans ; *Mesothelioma, Malignant/diagnostic imaging ; Prognosis ; Prospective Studies ; Fluorodeoxyglucose F18 ; Talc ; Radiopharmaceuticals ; Positron-Emission Tomography/methods ; *Mesothelioma/diagnostic imaging/drug therapy ; Positron Emission Tomography Computed Tomography/methods ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma is difficult to prognosticate. F18-Fluorodeoxyglucose positron emission tomography (FDG PET) shows promise for response assessment but is confounded by talc pleurodesis. F18-Fluorothymidine (FLT) PET is an alternative tracer specific for proliferation. We compared the prognostic value of FDG and FLT PET and determined the influence of talc pleurodesis on these parameters.

METHODS: Overall, 29 prospectively recruited patients had FLT PET, FDG PET and CT-scans performed prior to and post one chemotherapy cycle; 10 had prior talc pleurodesis. Patients were followed for overall survival. CT response was assessed using mRECIST. Radiomic features were extracted using the MiM software platform. Changes in maximum SUV (SUVmax), mean SUV (SUVmean), FDG total lesion glycolysis (TLG), FLT total lesion proliferation (TLP) and metabolic tumour volume (MTV) after one chemotherapy cycle.

RESULTS: Cox univariate analysis demonstrated FDG PET radiomics were confounded by talc pleurodesis, and that percentage change in FLT MTV was predictive of overall survival. Cox multivariate analysis showed a 10% increase in FLT tumour volume corresponded with 9.5% worsened odds for overall survival (P = 0.028, HR = 1.095, 95% CI [1.010, 1.187]). No other variables were significant on multivariate analysis.

CONCLUSION: This is the first prospective study showing the statistical significance of FLT PET tumour volumes for measuring mesothelioma treatment response. FLT may be better than FDG for monitoring mesothelioma treatment response, which could help optimise mesothelioma treatment regimes.}, } @article {pmid37894824, year = {2023}, author = {Leinardi, R and Petriglieri, JR and Pochet, A and Yakoub, Y and Lelong, M and Lescoat, A and Turci, F and Lecureur, V and Huaux, F}, title = {Distinct Pro-Inflammatory Mechanisms Elicited by Short and Long Amosite Asbestos Fibers in Macrophages.}, journal = {International journal of molecular sciences}, volume = {24}, number = {20}, pages = {}, pmid = {37894824}, issn = {1422-0067}, mesh = {Mice ; Animals ; *Asbestos, Amosite/toxicity ; Toll-Like Receptor 4 ; Macrophages ; *Asbestos/toxicity ; Apoptosis ; }, abstract = {While exposure to long amphibolic asbestos fibers (L > 10 µm) results in the development of severe diseases including inflammation, fibrosis, and mesothelioma, the pathogenic activity associated with short fibers (L < 5 µm) is less clear. By exposing murine macrophages to short (SFA) or long (LFA) fibers of amosite asbestos different in size and surface chemistry, we observed that SFA internalization resulted in pyroptotic-related immunogenic cell death (ICD) characterized by the release of the pro-inflammatory damage signal (DAMP) IL-1α after inflammasome activation and gasdermin D (GSDMD)-pore formation. In contrast, macrophage responses to non-internalizable LFA were associated with tumor necrosis factor alpha (TNF-α) release, caspase-3 and -7 activation, and apoptosis. SFA effects exclusively resulted from Toll-like receptor 4 (TLR4), a pattern-recognition receptor (PRR) recognized for its ability to sense particles, while the response to LFA was elicited by a multifactorial ignition system involving the macrophage receptor with collagenous structure (SR-A6 or MARCO), reactive oxygen species (ROS) cascade, and TLR4. Our findings indicate that asbestos fiber size and surface features play major roles in modulating ICD and inflammatory pathways. They also suggest that SFA are biologically reactive in vitro and, therefore, their inflammatory and toxic effects in vivo should not be underestimated.}, } @article {pmid37889448, year = {2023}, author = {Lee, FW and Chen, YH and Tran, ND and Lin, CK and Pham, LA}, title = {Association between Asbestos Exposure and the Incidence of Kidney Cancer: a Weight-of-Evidence Evaluation and Meta-analysis.}, journal = {Current environmental health reports}, volume = {10}, number = {4}, pages = {394-409}, pmid = {37889448}, issn = {2196-5412}, mesh = {Humans ; *Mesothelioma/chemically induced/epidemiology ; Incidence ; *Asbestos/toxicity ; Asbestos, Amphibole ; *Occupational Exposure/adverse effects ; *Kidney Neoplasms/chemically induced/epidemiology/complications ; }, abstract = {PURPOSE OF REVIEW: Occupational asbestos exposure has been extensively linked to various cancers, with ongoing debates regarding its association with kidney cancer. This study aims to investigate the correlation between occupational asbestos exposure and kidney cancer incidence. Additionally, potential influencing factors are analyzed to enhance the comprehension of the relationship between asbestos exposure and kidney cancer.

RECENT FINDING: While asbestos has established strong associations with malignant mesothelioma and lung cancer, its connection to other malignancies such as gastric, colorectal, and kidney cancers remains under scrutiny. The current study presents mixed opinions on the relationship between asbestos exposure and kidney cancer. Our analysis revealed a potential association between asbestos exposure and the incidence of kidney cancer. Notably, among different types of asbestos, exposure to amphibole appeared to be particularly linked to a higher incident risk of kidney cancer.}, } @article {pmid37880686, year = {2023}, author = {Carbone, M and Minaai, M and Takinishi, Y and Pagano, I and Yang, H}, title = {Preventive and therapeutic opportunities: targeting BAP1 and/or HMGB1 pathways to diminish the burden of mesothelioma.}, journal = {Journal of translational medicine}, volume = {21}, number = {1}, pages = {749}, pmid = {37880686}, issn = {1479-5876}, support = {R01 CA198138/CA/NCI NIH HHS/United States ; 1R01ES030948-01/ES/NIEHS NIH HHS/United States ; 1R01CA237235-01A1/CA/NCI NIH HHS/United States ; 1R01CA198138/CA/NCI NIH HHS/United States ; R01 ES030948/ES/NIEHS NIH HHS/United States ; }, mesh = {Humans ; *Asbestos/toxicity ; Carcinogenesis ; *HMGB1 Protein ; *Lung Neoplasms/genetics ; *Mesothelioma/epidemiology/therapy ; *Mesothelioma, Malignant/complications ; Tumor Suppressor Proteins/genetics/metabolism ; Ubiquitin Thiolesterase/genetics ; }, abstract = {Mesothelioma is a cancer typically caused by asbestos. Mechanistically, asbestos carcinogenesis has been linked to the asbestos-induced release of HMGB1 from the nucleus to the cytoplasm, where HMGB1 promotes autophagy and cell survival, and to the extracellular space where HMGB1 promotes chronic inflammation and mesothelioma growth. Targeting HMGB1 inhibited asbestos carcinogenesis and the growth of mesothelioma. It is hoped that targeting HMGB1 will be a novel therapeutic strategy that benefits mesothelioma patients. Severe restrictions and/or a complete ban on the use of asbestos were introduced in the 80 and early 90s in the Western world. These measures have proven effective as the incidence of mesothelioma/per 100,000 persons is decreasing in these countries. However, the overall number of mesotheliomas in the Western world has not significantly decreased. There are several reasons for that which are discussed here: (1) the presence of asbestos in old constructions; (2) the development of rural areas containing asbestos or other carcinogenic mineral fibers in the terrain; (3) the discovery of an increasing fraction of mesotheliomas caused by germline genetic mutations of BAP1 and other tumor suppressor genes; (4) mesotheliomas caused by radiation therapy; (5) the overall increase in the population and of the fraction of older people who are much more susceptible to develop all types of cancers, including mesothelioma. In summary, the epidemiology of mesothelioma is changing, the ban on asbestos worked, there are opportunities to help mesothelioma patients especially those who develop in a background of germline mutations and there is the opportunity to prevent a mesothelioma epidemic in the developing world, where the use of asbestos is increasing exponentially. We hope that restrictive measures similar to those introduced in the Western world will soon be introduced in developing countries to prevent a mesothelioma epidemic.}, } @article {pmid37878258, year = {2023}, author = {Vimercati, L and Cavone, D and Negrisolo, O and Pentimone, F and De Maria, L and Caputi, A and Sponselli, S and Delvecchio, G and Cafaro, F and Chellini, E and Binazzi, A and Di Marzio, D and Mensi, C and Consonni, D and Migliore, E and Brentisci, C and Martini, A and Negro, C and D'Agostin, F and Grappasonni, I and Pascucci, C and Benfatto, L and Malacarne, D and Casotto, V and Comiati, V and Storchi, C and Mangone, L and Murano, S and Rossin, L and Tallarigo, F and Vitale, F and Verardo, M and Eccher, S and Madeo, G and Staniscia, T and Carrozza, F and Cozzi, I and Romeo, E and Pelullo, P and Labianca, M and Melis, M and Cascone, G and Ferri, GM and Serio, G}, title = {Mesothelioma Risk Among Maritime Workers According to Job Title: Data From the Italian Mesothelioma Register (ReNaM).}, journal = {La Medicina del lavoro}, volume = {114}, number = {5}, pages = {e2023038}, pmid = {37878258}, issn = {0025-7818}, mesh = {Male ; Humans ; *Mesothelioma, Malignant ; *Mesothelioma/epidemiology/etiology ; *Military Personnel ; Italy/epidemiology ; *Asbestos/adverse effects ; }, abstract = {The study describes the 466 cases of malignant mesotheliomas (MM) collected by the National Mesothelioma Register (ReNaM) in Italy in the period 1993-2018 relating to subjects with exclusive asbestos exposure in merchant or military navy. The cases among maritime workers represent 1.8% of the total cases with defined exposure registred in the ReNaM, of which 212 cases (45.4%) among merchant maritime workers and 254 cases (54.5%) among navy. The distribution by site of mesothelioma showed 453 (97.2%) MM cases of the pleura, 11 (2.3%) of the peritoneum and 2 (0.4%) of the tunica vaginalis of the testis. With regard to occupational exposure, it was classified as certain in 318 (68.2%) cases, probable in 69 (14.8%) cases and possible in 79 (16.9%) cases. Among the 23 classified jobs, the highest percentages of certain exposures are among naval engineers, motor mechanics, machine captains and sailors. Machine crew accounted for 49.3% of the cases, deck crew for 27.6%. All cases began exposure on board between 1926 and 1988. Seamen were exposed to asbestos while at sea by virtue of living onboard ships and from continual release of asbestos fibers due to the motion of a vessel. Epidemiological surveillance through the ReNaM has allowed us to verify among cases in the maritime, navy and merchant marine sectors, that in the past, subjects were exposed regardless of the ship's department where have provided service therefore all these cases must be considered as occupational diseases.}, } @article {pmid37873988, year = {2023}, author = {Bolgeo, T and Di Matteo, R and Crivellari, S and Gatti, D and Cassinari, A and Riccio, C and De Angelis, A and Delfanti, S and Ferrero, E and Gnani, C and Riili, G and Maconi, A}, title = {Quality of life in patients with PICC diagnosed with mesothelioma: Results of a multicenter epidemiological survey (LifePICC).}, journal = {The journal of vascular access}, volume = {}, number = {}, pages = {11297298231202046}, doi = {10.1177/11297298231202046}, pmid = {37873988}, issn = {1724-6032}, abstract = {BACKGROUND: Pleural mesothelioma (PM) is a rare and aggressive cancer. PICC devices are widely used in cancer patients. The aim of the study is to evaluate the quality of life of patients with PICC diagnosed with PM treated at the Hospital of Casale Monferrato and Alessandria (Italy), an area with a high incidence of asbestos-related diseases.

STUDY DESIGN AND METHODS: Longitudinal prospective observational study with data collection at PICC insertion (T0), after 3 months (T1), 6 months (T2), and 9 months (T3). Participants were aged >18 years, diagnosed with PM, eligible for PICC insertion. Questionnaires used: EORTC QLQ-C30, EORTC QLQ-LC13, and HADS rating scale.

RESULTS: Twenty-eight patients were enrolled. The mean age was 68.93 years (SD 9.13), mostly male (57.1%). The most frequent cancer stage at diagnosis was III (39.3%), then I (32.1%), and IV (21.4%). 85.7% were treated with chemotherapy, 14.3% also with immunotherapy. 96.4% of patients reported no complications during PICC implantation. The perception of health status and quality of life, measured on a scale of 1-7, was in line with an average score of 5 during the evaluation period. The total anxiety and depression score remained normal for most patients (0-7).

CONCLUSIONS: The PICC management involved a multidisciplinary team with different skills: study findings revealed the key role that dedicated nurses play in PICC placement and ensuring patient problems are promptly addressed. From our study results, PICC placement does not seem to negatively impact the patient's quality of life.}, } @article {pmid37855384, year = {2024}, author = {Ferrante, D and Angelini, A and Barbiero, F and Barbone, F and Bauleo, L and Binazzi, A and Bovenzi, M and Bruno, C and Casotto, V and Cernigliaro, A and Ceppi, M and Cervino, D and Chellini, E and Curti, S and De Santis, M and Fazzo, L and Fedeli, U and Fiorillo, G and Franchi, A and Gangemi, M and Giangreco, M and Rossi, PG and Girardi, P and Luberto, F and Massari, S and Mattioli, S and Menegozzo, S and Merlo, DF and Michelozzi, P and Migliore, E and Miligi, L and Oddone, E and Pernetti, R and Perticaroli, P and Piro, S and Addario, SP and Romeo, E and Roncaglia, F and Silvestri, S and Storchi, C and Zona, A and Magnani, C and Marinaccio, A}, title = {Cause specific mortality in an Italian pool of asbestos workers cohorts.}, journal = {American journal of industrial medicine}, volume = {67}, number = {1}, pages = {31-43}, doi = {10.1002/ajim.23546}, pmid = {37855384}, issn = {1097-0274}, support = {//This work was supported by the 'INAIL BRIC project 2019-2021"; INAIL (Piano Ricerca 2016-2018, "Programma Speciale Amianto, BRIC id 55 and BRIC id 59) and 'Asbestos Project' organized by the Italian National Institute of Health (ISS) (Ricerca corrente 2012: Progetto amianto)./ ; }, mesh = {Male ; Humans ; Female ; Cause of Death ; *Mesothelioma/etiology ; Cohort Studies ; *Occupational Exposure/adverse effects ; *Occupational Diseases/etiology ; Construction Materials ; *Asbestos/adverse effects ; *Pleural Neoplasms ; *Peritoneal Neoplasms ; *Ovarian Neoplasms ; Italy/epidemiology ; *Lung Neoplasms/etiology ; }, abstract = {BACKGROUND: Asbestos is a known human carcinogen and is causally associated with malignant mesothelioma, lung, larynx and ovarian cancers.

METHODS: Cancer risk was studied among a pool of formerly asbestos-exposed workers in Italy. Fifty-two Italian asbestos cohorts (asbestos-cement, rolling-stock, shipbuilding, and other) were pooled and their mortality follow-up was updated to 2018. Standardized mortality ratios (SMRs) were computed for major causes of death considering duration of exposure and time since first exposure (TSFE), using reference rates by region, age and calendar period.

RESULTS: The study included 63,502 subjects (57,156 men and 6346 women): 40% who were alive, 58% who died (cause known for 92%), and 2% lost to follow-up. Mortality was increased for all causes (SMR: men = 1.04, 95% confidence interval [CI] 1.03-1.05; women = 1.15, 95% CI 1.11-1.18), all malignancies (SMR: men = 1.21, 95% CI 1.18-1.23; women = 1.29, 95% CI 1.22-1.37), pleural and peritoneal malignancies (men: SMR = 10.46, 95% CI 9.86-11.09 and 4.29, 95% CI 3.66-5.00; women: SMR = 27.13, 95% CI 23.29-31.42 and 7.51, 95% CI 5.52-9.98), lung (SMR: men = 1.28, 95% CI 1.24-1.32; women = 1.26, 95% CI 1.02-1.53), and ovarian cancer (SMR = 1.42, 95% CI 1.08-1.84). Pleural cancer mortality increased during the first 40 years of TSFE (latency), reaching a plateau thereafter.

CONCLUSIONS: Analyses by time-dependent variables showed that the risk for pleural neoplasms increased with latency and no longer increases at long TSFE, consistent with with asbestos clearance from the lungs. Peritoneal neoplasm risk increased over all observation time.}, } @article {pmid37850051, year = {2023}, author = {Nishida, S and Toriyama, K and Yomota, M and Hosomi, Y}, title = {Malignant pleural mesothelioma with resolution of pleural effusion.}, journal = {Respirology case reports}, volume = {11}, number = {11}, pages = {e01234}, pmid = {37850051}, issn = {2051-3380}, abstract = {In malignant pleural mesothelioma patients, pleural effusion may improve during the course of the disease. Pleural effusion with nodular shadows bordering the pleura should be followed up even if the pleural effusion improves.}, } @article {pmid37846453, year = {2023}, author = {Silvestri, S and Carnevale, F and Cavariani, F and Deidda, B}, title = {[The assessment of asbestos exposure of mesothelioma cases registered in Italy: which problems more than thirty years after the birth of the first regional archives].}, journal = {Epidemiologia e prevenzione}, volume = {47}, number = {4-5}, pages = {298-305}, doi = {10.19191/EP23.4-5.A617.070}, pmid = {37846453}, issn = {1120-9763}, mesh = {Humans ; *Occupational Exposure/adverse effects ; Population Surveillance ; Italy/epidemiology ; Registries ; *Mesothelioma/epidemiology/etiology ; *Mesothelioma, Malignant ; *Asbestos/toxicity ; *Pleural Neoplasms/diagnosis/epidemiology/etiology ; }, abstract = {More than 30 years have passed since the beginning of the epidemiological surveillance of mesothelioma (MM). The Italian National Mesothelioma Register (ReNaM), part of the research department of the National Institute for insurance against industrial injuries (INAIL), has published 7 reports with the description of the cas-es concerning the assessment of diagnoses and exposures to asbestos suffered mainly during working activities but also environmental, in the family premises and during personal activities.Today we are witnessing a reduction in the commitment by some regions which negatively affects those who develop the pathology. Reading the ReNaM reports it emerges, among others, the problem of the delay in reporting new cases which limits the collection of information directly from patients. This contribution, discussing various topics, invites to develop a debate that should allow to update and resolve the critical aspects that arise after decades of activity regarding, in particular, the asbestos exposure assessment. It is the primary interest of the authors to give continuity and improve the ReNaM which remains the most prestigious MM register among those active in other countries.}, } @article {pmid37846448, year = {2023}, author = {Angelini, A and Martini, A and Begliomini, B and Silvestri, S}, title = {[Malignant mesothelioma in two married couples exposed to asbestos].}, journal = {Epidemiologia e prevenzione}, volume = {47}, number = {4-5}, pages = {257-262}, doi = {10.19191/EP23.4-5.A623.065}, pmid = {37846448}, issn = {1120-9763}, mesh = {Humans ; Female ; *Mesothelioma, Malignant ; *Mesothelioma/chemically induced/diagnosis/epidemiology ; Spouses ; *Occupational Exposure/adverse effects ; *Pleural Neoplasms/epidemiology ; Italy/epidemiology ; *Asbestos/toxicity ; *Lung Neoplasms/chemically induced/diagnosis/epidemiology ; *Occupational Diseases/epidemiology ; }, abstract = {BACKGROUND: the relationship between past asbestos exposure and the onset of malignant mesothelioma (MM) is well established. However, defining the exposure is not always easy, as it occurs decades before the onset of the disease.

OBJECTIVES: this report describes four cases of MM diagnosed in two different married couples, both exposed to asbestos fibers: husbands at work and wives for cohabiting and washing their work overalls.

DESIGN: case report.

METHODS: the information was collected through interviews using a semi-structured questionnaire and analyzed by occupational hygienists during the activity of epidemiological surveillance of this disease. The results of the mineral content of asbestos fibers performed on lung parenchymal from one of the female cases are available.

RESULTS: these two cases show a longer latency in the lesser exposed confirming what an occupational epidemiological study has recently highlighted.

CONCLUSIONS: whenever good quality information collected during interviews are available, skilled occupational hygienists are able to reconstruct past exposures in quali-quantitative terms.}, } @article {pmid37845104, year = {2023}, author = {Kaplan, MA and Şendur, MAN and Cangır, AK and Fırat, P and Göker, E and Kılıçkap, S and Oyan, B and Büge Öz, A and Özdemir, F and Özyiğit, G}, title = {Established and new treatment roadmaps for pleural mesothelioma: opinions of the Turkish Collaborative Group.}, journal = {Current problems in cancer}, volume = {47}, number = {6}, pages = {101017}, doi = {10.1016/j.currproblcancer.2023.101017}, pmid = {37845104}, issn = {1535-6345}, mesh = {Humans ; Immunotherapy ; *Mesothelioma/therapy/drug therapy ; Pleura/pathology ; *Pleural Neoplasms/therapy/drug therapy ; Turkey/epidemiology ; }, abstract = {Pleural mesothelioma (PM) is a cancer of the pleural surface, which is aggressive and may be rapidly fatal. PM is a rare cancer worldwide, but is a relatively common disease in Turkey. Asbestos exposure is the main risk factor and the most common underlying cause of the disease. There have been significant improvements in diagnoses and treatments of many malignancies; however, there are still therapeutic challenges in PM. In this review, we aimed to increase the awareness of health care professionals, oncologists, and pulmonologists by underlining the unmet needs of patients with PM and by emphasizing the need for a multidisciplinary treatment and management of PM. After reviewing the general information about PM, we further discuss the treatment options for patients with PM using immunotherapy and offer evidence for improvements in the clinical outcomes of these patients because of these newer treatment modalities.}, } @article {pmid37813485, year = {2023}, author = {Marinaccio, A and Di Marzio, D and Mensi, C and Consonni, D and Gioscia, C and Migliore, E and Genova, C and Rossetto Giaccherino, R and Eccher, S and Murano, S and Comiati, V and Casotto, V and Negro, C and Mangone, L and Miligi, L and Piro, S and Angelini, A and Grappasonni, I and Madeo, G and Cozzi, I and Ancona, L and Staniscia, T and Carrozza, F and Cavone, D and Vimercati, L and Labianca, M and Tallarigo, F and Cascone, G and Melis, M and Bonafede, M and Scarselli, A and Binazzi, A}, title = {Incidence of mesothelioma in young people and causal exposure to asbestos in the Italian national mesothelioma registry (ReNaM).}, journal = {Occupational and environmental medicine}, volume = {80}, number = {11}, pages = {603-609}, doi = {10.1136/oemed-2023-108983}, pmid = {37813485}, issn = {1470-7926}, mesh = {Humans ; Adolescent ; Middle Aged ; *Mesothelioma, Malignant/complications ; Incidence ; *Mesothelioma/epidemiology/etiology ; *Asbestos/adverse effects ; *Occupational Exposure/adverse effects ; Italy/epidemiology ; Registries ; *Pleural Neoplasms/epidemiology/etiology ; }, abstract = {INTRODUCTION: The epidemiological surveillance of mesothelioma incidence is a crucial key for investigating the occupational and environmental sources of asbestos exposure. The median age at diagnosis is generally high, according to the long latency of the disease. The purposes of this study are to analyse the incidence of mesothelioma in young people and to evaluate the modalities of asbestos exposure.

METHODS: Incident malignant mesothelioma (MM) cases in the period 1993-2018 were retrieved from Italian national mesothelioma registry and analysed for gender, incidence period, morphology and exposure. Age-standardised rates have been calculated and the multiple correspondence analysis has been performed. The association between age and asbestos exposure has been tested by χ[2] test.

RESULTS: From 1993 to 2018, 30 828 incident MM cases have been collected and 1278 (4.1%) presented diagnosis at early age (≤50 years). There is a substantial association between age at diagnosis and the type of asbestos exposure and a significantly lower frequency of cases with occupational exposure to asbestos (497 cases vs 701 expected) in young people has been documented. Paraoccupational and environmental exposure to asbestos have been found more frequent in young MM cases (85 and 93 observed cases vs 52 and 44 expected cases, respectively).

CONCLUSIONS: Mesothelioma incidence surveillance at population level and the anamnestic individual research of asbestos exposure is a fundamental tool for monitoring asbestos exposure health effects, supporting the exposure risks prevention policies. Clusters of mesothelioma incident cases in young people are a significant signal of a potential non-occupational exposure to asbestos.}, } @article {pmid37824368, year = {2024}, author = {Tuncel, T and Metintas, M and Güntülü, AK and Güneş, HV}, title = {Whole-Genome Comparative Copy Number Alteration Profiling between Malignant Pleural Mesothelioma and Asbestos-Induced Chronic Pleuritis.}, journal = {Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer}, volume = {43}, number = {1}, pages = {31-44}, doi = {10.1615/JEnvironPatholToxicolOncol.2023047755}, pmid = {37824368}, issn = {2162-6537}, mesh = {Humans ; *Mesothelioma, Malignant ; DNA Copy Number Variations ; *Asbestos/toxicity ; *Pleurisy/genetics ; }, abstract = {Malignant pleural mesothelioma (MPM) is rare and aggressive cancer. The most important risk factor for MPM is exposure to asbestos. In this study, we scanned the genomes of individuals MPM and asbestos-induced chronic pleuritis (AICP) to compare and determine copy number alterations (CNAs) between two asbestos-related diseases. We used high-resolution SNP arrays to compare CNA profiles between MPM (n = 55) and AICP (n = 18). DNAs extracted from pleural tissues in both groups. SNP array analysis revealed common losses at 1p, 3p, 6q, 9p, 13q, 14q, 15q, 16q, 22q and frequent gains at chromosomes 1, 3, 5, 7, 8, and 6p, 12q, 15q, 17p, 20q in MPMs (frequencies max 67%-min 30%; these alterations were not detected in AICPs. Besides detecting well-known MPM-associated CNAs, our high -resolution copy number profiling also detected comparatively rare CNAs for MPMs including losses like 9q33.3, 16q and gains of 1p, 1q, 3p, 3q, 6p, 7q, 15q, 12q, 17p, 20q at significant frequencies in the MPM cohort. We also observed Copy Number gains clustered on the NF2 locus in AICPs, whereas this region was commonly deleted in MPMs. According to this distinct genomic profiles between the two groups, AICPs genomes can be clearly distinguished from highly altered MPM genomes. Hence, we can suggest that SNP arrays can be used as a supporting diagnostic tool in terms of discriminating asbestos-related malignant disease such as MPM and benign pleural lesions, which can be challenging in most instances.}, } @article {pmid37811036, year = {2023}, author = {Mehta, K and Mehta, S and Joshi, M and Bharadwaj, HR and Ardeshana, G and Tenkorang, PO}, title = {Challenging diagnosis of sarcomatoid hepatic mesothelioma: a case report with review of literature.}, journal = {Annals of medicine and surgery (2012)}, volume = {85}, number = {10}, pages = {5123-5126}, pmid = {37811036}, issn = {2049-0801}, abstract = {INTRODUCTION: Mesothelioma is a rare and aggressive cancer that is primarily caused by asbestos exposure. However, cases of mesothelioma without asbestos exposure suggest the involvement of other risk factors. Sarcomatoid mesothelioma, which is characterized by spindle-shaped cells, is a particularly aggressive subtype with limited treatment options.

CASE PRESENTATION: The authors present a case of a 72-year-old man with no history of asbestos exposure who presented with abdominal pain, fatigue, and weight loss. Imaging revealed a large cystic mass in the liver. A Liver biopsy confirmed the diagnosis of sarcomatoid mesothelioma. Immunohistochemistry results further supported this diagnosis. Due to the advanced stage and tumor size, surgical resection was not feasible. Palliative chemotherapy was initiated, but the patient's condition deteriorated rapidly, leading to his demise.

CONCLUSION: This case highlights the complexity of mesothelioma and the need for further research to identify the nonasbestos-related risk factors. Understanding alternative causative agents and mechanisms is crucial for the early detection, the development of targeted therapies, and improving patient outcomes. The presented case contributes to the existing literature and aligns with the Surgical CAse REport (SCARE) Criteria.}, } @article {pmid37810608, year = {2023}, author = {Ramos-Bonilla, JP and Giraldo, M and Marsili, D and Pasetto, R and Terracini, B and Mazzeo, A and Magnani, C and Comba, P and Lysaniuk, B and Cely-García, MF and Ascoli, V}, title = {An Approach to Overcome the Limitations of Surveillance of Asbestos Related Diseases in Low- and Middle-Income Countries: What We Learned from the Sibaté Study in Colombia.}, journal = {Annals of global health}, volume = {89}, number = {1}, pages = {64}, pmid = {37810608}, issn = {2214-9996}, mesh = {Humans ; Colombia/epidemiology ; Developing Countries ; *Occupational Exposure/adverse effects ; *Asbestos ; *Mesothelioma/epidemiology ; *Mesothelioma, Malignant ; *Respiratory Distress Syndrome ; }, abstract = {INTRODUCTION: The asbestos industry began its operations in Colombia in 1942 with the establishment of an asbestos-cement facility in Sibaté, located in the Department of Cundinamarca. Despite extensive asbestos use and production in Colombia, the country lacks a reliable epidemiological surveillance system to monitor the health effects of asbestos exposure. The Colombian health information system, known as SISPRO, did not report mesothelioma cases diagnosed in the municipality, posing a significant challenge in understanding the health impacts of asbestos exposure on the population of Sibaté.

METHODS: To address this issue, an active surveillance strategy was implemented in Sibaté. This strategy involved conducting door-to-door health and socioeconomic structured interviews to identify Asbestos-Related Diseases (ARDs). Validation strategies included a thorough review of medical records by a panel of physicians, and the findings were communicated to local, regional, and national authorities, as well as the general population.

RESULTS: The active surveillance strategy successfully identified a mesothelioma cluster in Sibaté, revealing the inadequacy of the existing health information system in monitoring asbestos-related diseases. The discovery of this cluster underscores the critical importance of implementing active surveillance strategies in Colombia, where governmental institutions and resources are often limited.

CONCLUSION: The findings of this study emphasize the urgent need for Colombia to establish a reliable epidemiological surveillance system for asbestos-related diseases (ARDs). Active surveillance strategies can play a crucial role in identifying mesothelioma clusters and enhancing our understanding of the health effects of asbestos exposure in low- and middle-income countries.}, } @article {pmid37802348, year = {2024}, author = {Takefuji, Y}, title = {An urgent call to action: The absolute necessity to ban asbestos production and sales.}, journal = {The Science of the total environment}, volume = {906}, number = {}, pages = {167557}, doi = {10.1016/j.scitotenv.2023.167557}, pmid = {37802348}, issn = {1879-1026}, mesh = {Humans ; *Occupational Exposure ; *Asbestos ; *Mesothelioma/epidemiology ; Health Policy ; Dust ; }, abstract = {The issue with asbestos highlights the shortcomings in the global management of health policies for dangerous substances. The perils of asbestos dust were identified about a century ago. A significant number of individuals succumb to asbestos-related diseases worldwide annually. A considerable portion of occupational cancer fatalities are believed to be due to asbestos. A large population across the globe is exposed to asbestos in their workplaces. To address issues like asbestos, it is crucial for policymakers to prioritize public interest, and third parties should actively participate in scrutinizing the actions of these policymakers.}, } @article {pmid37800384, year = {2023}, author = {Sahin, ER and Koksal, D}, title = {Asbestos: Mineralogical features and fiber analysis in biological materials.}, journal = {Archives of environmental & occupational health}, volume = {78}, number = {6}, pages = {369-378}, doi = {10.1080/19338244.2023.2264764}, pmid = {37800384}, issn = {2154-4700}, mesh = {Humans ; *Asbestos ; *Mesothelioma/chemically induced ; *Asbestosis/etiology ; *Lung Neoplasms/chemically induced ; *Mesothelioma, Malignant/complications ; }, abstract = {Asbestos is a mineral with unique physical and chemical properties that make it highly resistant to heat, fire, and corrosion. Nevertheless, exposure to asbestos fibers has been linked to serious health problems, including lung cancer, mesothelioma, and asbestosis. Despite the ban on asbestos usage, asbestos-related diseases are still a major cause of morbidity and mortality worldwide. Analyzing the mineralogical features and fiber analysis of asbestos in biological materials is critical for scenarios where an asbestos exposure history cannot be obtained, a clinical diagnosis cannot be made, or legal aspects necessitate further investigation. This review outlines the mineralogical features and fiber analysis techniques of asbestos in biological materials.}, } @article {pmid37793939, year = {2023}, author = {Ibnian, AM and Khan, OU and Chan, R and Bangalore Lakshminarayana, U and Kiran, F and Abed, S and Abbas, R and Amir, A and Al-Kofahi, NK}, title = {Gelatinous Pleural Effusion: A Diagnostic Challenge for Pleural Mesothelioma in an 80-Year-Old Man.}, journal = {The American journal of case reports}, volume = {24}, number = {}, pages = {e941263}, pmid = {37793939}, issn = {1941-5923}, mesh = {Male ; Humans ; Aged, 80 and over ; *Mesothelioma/diagnosis/pathology ; *Pleural Neoplasms/diagnosis ; *Pleural Effusion/diagnostic imaging/etiology ; Pleura/pathology ; *Asbestos ; *Pleural Diseases ; }, abstract = {BACKGROUND Gelatinous pleural effusion, due to raised hyaluronic acid, can be associated with pleural infection and malignancies, such as tuberculosis, metastatic pleural disease, and mesothelioma. This report is of an 80-year-old man presenting with a gelatinous pleural effusion and diagnosis of pleural mesothelioma. CASE REPORT An 80-year-old man with diabetes mellitus, ischemic heart disease, metastatic prostate cancer, 30-pack-year smoking history, and 5-year history of asbestos exposure (during his 30s), presented with a 4-week history of breathlessness and was found to have right-sided pleural effusion. Thoracic computed tomography (CT) showed mild right-sided pleural thickening. Pleural tap revealed exudative fluid, with a pH of 7.4, and unremarkable cytology and microbiology analyses. The patient was treated for pneumonia and para-pneumonic effusion and discharged home. He came back 5 weeks later with worsening of symptoms and re-accumulation of pleural fluid. Repeated thorax CT showed extensive right-sided pleural lobular thickening. Pleural tap again yielded an exudative fluid, with a pH of 7.37. Cytology and microbiology did not reveal any positive signs for malignancy or infection. This time the pleural fluid appeared gelatinous in consistency. Pleural biopsy showed atypical epithelioid mesothelial cells arranged in trabeculae, with a tubulo-papillary configuration. Also, immunohistochemistry panel showed tumor cells expressed calretinin, EMA, WT1, and D2-40, with negative TTF1, CEA, and BerEp4. Final diagnosis was epithelioid mesothelioma. CONCLUSIONS This report has shown that a gelatinous pleural effusion can be associated with malignant and inflammatory pleural diseases. In this case, imaging and pleural biopsy with histopathology confirmed a diagnosis of pleural mesothelioma.}, } @article {pmid37730104, year = {2023}, author = {Schelch, K and Emminger, D and Zitta, B and Johnson, TG and Kopatz, V and Eder, S and Ries, A and Stefanelli, A and Heffeter, P and Hoda, MA and Hoetzenecker, K and Dome, B and Berger, W and Reid, G and Grusch, M}, title = {Targeting YB-1 via entinostat enhances cisplatin sensitivity of pleural mesothelioma in vitro and in vivo.}, journal = {Cancer letters}, volume = {574}, number = {}, pages = {216395}, doi = {10.1016/j.canlet.2023.216395}, pmid = {37730104}, issn = {1872-7980}, support = {DOC 59/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {*Cisplatin/pharmacology ; Animals ; Humans ; *Pyridines/pharmacology ; *Benzamides/pharmacology ; Cell Line, Tumor ; *Y-Box-Binding Protein 1/metabolism/genetics ; *Pleural Neoplasms/drug therapy/pathology/genetics/metabolism ; *Xenograft Model Antitumor Assays ; *Drug Synergism ; *Mesothelioma/drug therapy/pathology/metabolism/genetics ; Mice ; Cell Proliferation/drug effects ; Antineoplastic Combined Chemotherapy Protocols/pharmacology/therapeutic use ; Mice, Nude ; Antineoplastic Agents/pharmacology ; Acetylation ; Female ; Tumor Suppressor Proteins ; Ubiquitin Thiolesterase ; }, abstract = {Pleural mesothelioma (PM) is characterized by poor prognosis and limited therapeutic options. Y-box-binding protein 1 (YB-1) was shown to drive growth and migration of PM cells. Here, we evaluated the effect of genetic and pharmacological targeting of YB-1 on PM growth and response to cisplatin and radiation treatment. YB-1 knockdown via siRNA resulted in reduced PM cell growth, which significantly correlated with wt BAP1 and mutant NF2 and P53 status. Entinostat inhibited YB-1 deacetylation and its efficacy correlated with YB-1 knockdown-induced growth inhibition in 20 PM cell lines. Tumor growth inhibition by siRNA as well as entinostat was confirmed in mouse xenotransplant models. Furthermore, both YBX1-targeting siRNA and entinostat enhanced sensitivity to cisplatin and radiation. In particular, entinostat showed strong synergistic interactions with cisplatin which was linked to significantly increased cellular platinum uptake in all investigated cell models. Importantly, in a mouse model, the combination of cisplatin and entinostat also resulted in stronger growth inhibition than each treatment alone. Our study highlights YB-1 as an attractive target in PM and demonstrates that targeting YB-1 via entinostat is a promising approach to enhance cisplatin and radiation sensitivity.}, } @article {pmid37729199, year = {2023}, author = {Suarez, JS and Novelli, F and Goto, K and Ehara, M and Steele, M and Kim, JH and Zolondick, AA and Xue, J and Xu, R and Saito, M and Pastorino, S and Minaai, M and Takanishi, Y and Emi, M and Pagano, I and Wakeham, A and Berger, T and Pass, HI and Gaudino, G and Mak, TW and Carbone, M and Yang, H}, title = {HMGB1 released by mesothelial cells drives the development of asbestos-induced mesothelioma.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {120}, number = {39}, pages = {e2307999120}, pmid = {37729199}, issn = {1091-6490}, support = {R01 CA198138/CA/NCI NIH HHS/United States ; S10 OD028515/OD/NIH HHS/United States ; R01 CA237235/CA/NCI NIH HHS/United States ; U01 CA214195/CA/NCI NIH HHS/United States ; R01 ES030948/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Mice ; *Mesothelioma, Malignant ; Tumor Necrosis Factor-alpha/genetics ; *HMGB1 Protein/genetics ; *Mesothelioma/chemically induced/genetics ; *Asbestos/toxicity ; Inflammation ; Tumor Microenvironment ; }, abstract = {Asbestos is the main cause of malignant mesothelioma. Previous studies have linked asbestos-induced mesothelioma to the release of HMGB1 from the nucleus to the cytoplasm, and from the cytoplasm to the extracellular space. In the cytoplasm, HMGB1 induces autophagy impairing asbestos-induced cell death. Extracellularly, HMGB1 stimulates the secretion of TNFα. Jointly, these two cytokines kick-start a chronic inflammatory process that over time promotes mesothelioma development. Whether the main source of extracellular HMGB1 were the mesothelial cells, the inflammatory cells, or both was unsolved. This information is critical to identify the targets and design preventive/therapeutic strategies to interfere with asbestos-induced mesothelioma. To address this issue, we developed the conditional mesothelial HMGB1-knockout (Hmgb1[ΔpMeso]) and the conditional myelomonocytic-lineage HMGB1-knockout (Hmgb1[ΔMylc]) mouse models. We establish here that HMGB1 is mainly produced and released by the mesothelial cells during the early phases of inflammation following asbestos exposure. The release of HMGB1 from mesothelial cells leads to atypical mesothelial hyperplasia, and in some animals, this evolves over the years into mesothelioma. We found that Hmgb1[ΔpMeso], whose mesothelial cells cannot produce HMGB1, show a greatly reduced inflammatory response to asbestos, and their mesothelial cells express and secrete significantly reduced levels of TNFα. Moreover, the tissue microenvironment in areas of asbestos deposits displays an increased fraction of M1-polarized macrophages compared to M2 macrophages. Supporting the biological significance of these findings, Hmgb1[ΔpMeso] mice showed a delayed and reduced incidence of mesothelioma and an increased mesothelioma-specific survival. Altogether, our study provides a biological explanation for HMGB1 as a driver of asbestos-induced mesothelioma.}, } @article {pmid37722697, year = {2024}, author = {Febres-Aldana, CA and Fanaroff, R and Offin, M and Zauderer, MG and Sauter, JL and Yang, SR and Ladanyi, M}, title = {Diffuse Pleural Mesothelioma: Advances in Molecular Pathogenesis, Diagnosis, and Treatment.}, journal = {Annual review of pathology}, volume = {19}, number = {}, pages = {11-42}, doi = {10.1146/annurev-pathol-042420-092719}, pmid = {37722697}, issn = {1553-4014}, mesh = {Humans ; *Mesothelioma ; Risk Factors ; }, abstract = {Diffuse pleural mesothelioma (DPM) is a highly aggressive malignant neoplasm arising from the mesothelial cells lining the pleural surfaces. While DPM is a well-recognized disease linked to asbestos exposure, recent advances have expanded our understanding of molecular pathogenesis and transformed our clinical practice. This comprehensive review explores the current concepts and emerging trends in DPM, including risk factors, pathobiology, histologic subtyping, and therapeutic management, with an emphasis on a multidisciplinary approach to this complex disease.}, } @article {pmid37712235, year = {2023}, author = {Bruno, C and Di Stefano, R and Ricceri, V and La Rosa, M and Cernigliaro, A and Ciranni, P and Di Maria, G and Mandrioli, D and Zona, A and Comba, P and Scondotto, S}, title = {Fluoro-edenite non-neoplastic diseases in Biancavilla (Sicily, Italy): pleural plaques and/or pneumoconiosis?.}, journal = {Annali dell'Istituto superiore di sanita}, volume = {59}, number = {3}, pages = {187-193}, doi = {10.4415/ANN_23_03_03}, pmid = {37712235}, issn = {2384-8553}, mesh = {Humans ; Sicily/epidemiology ; *Asbestosis/diagnostic imaging/epidemiology ; Asbestos, Amphibole/toxicity ; Italy/epidemiology ; *Pneumoconiosis/diagnostic imaging/epidemiology ; *Mesothelioma/diagnostic imaging/epidemiology ; }, abstract = {BACKGROUND: A mesothelioma cluster in Biancavilla (Sicily, Italy), drew attention to fluoro-edenite, a fibre classified by International Agency for Research on Cancer as carcinogenic to humans. Significant excesses in mortality and morbidity were observed for respiratory diseases and a significant excess of pneumoconiosis hospitalizations was reported.

OBJECTIVE: Aim of this study is to assess the characters of the lung damage in Biancavilla residents hospitalized with pneumoconiosis or asbestosis diagnoses.

METHODOLOGY: Medical records, available radiographs and computed tomography scans were collected. The obtained imaging was reviewed by a panel of three specialists and focused on pleural and parenchymal abnormalities. Cases with an ILO-BIT or ICOERD score equal or greater than 2 were considered positive for a pneumoconiosis-like damage, cases with a score lower than 2 or insufficient quality of imaging were considered inconclusive. If no pneumoconiotic aspects were present the cases were classified as negative.

RESULTS: Out of 38 cases, diagnostic imaging for 25 cases were found. Ten cases out of 25 showed asbestosis-like features, nine subjects were considered negative. In six patients' results were inconclusive.

CONCLUSIONS: Asbestosis-like features were substantiated in Biancavilla residents without known occupational exposure to asbestos. Further studies to estimate population respiratory health are required. Experimental studies on the fibrogenic potential of fluoro-edenite are needed.}, } @article {pmid37692737, year = {2023}, author = {Alsalihi, Y and Kandaswamy, C}, title = {A Worsening Cough: An Unusual Presentation of Malignant Mesothelioma.}, journal = {Cureus}, volume = {15}, number = {8}, pages = {e43205}, pmid = {37692737}, issn = {2168-8184}, abstract = {Localized malignant pleural mesothelioma (LMPM) is a rare cancer with poor survival rates. Often affecting males with asbestos exposure, we report a case of a 56-year-old female with no history of occupational exposure presenting with a worsening cough. A radiological examination revealed left pleural effusion and pleural thickening. Cytological and pathological reports of pleural samples were consistent with malignant mesothelioma of epithelioid type, with the histological examination via video-assisted thoracoscopic surgery (VATS) consistent with a clear cell epithelioid mesothelioma. We discuss the rapid presentation of the disease with emphasis on considering the disease in young patients with no prior asbestos exposure.}, } @article {pmid37683624, year = {2023}, author = {Zwijsen, K and Schillebeeckx, E and Janssens, E and Cleemput, JV and Richart, T and Surmont, VF and Nackaerts, K and Marcq, E and van Meerbeeck, JP and Lamote, K}, title = {Determining the clinical utility of a breath test for screening an asbestos-exposed population for pleural mesothelioma: baseline results.}, journal = {Journal of breath research}, volume = {17}, number = {4}, pages = {}, doi = {10.1088/1752-7163/acf7e3}, pmid = {37683624}, issn = {1752-7163}, mesh = {Humans ; Breath Tests ; *Mesothelioma/diagnostic imaging ; *Pleural Neoplasms/diagnostic imaging ; *Asbestos/adverse effects ; *Body Fluids ; }, abstract = {Pleural mesothelioma (PM) is an aggressive cancer of the serosal lining of the thoracic cavity, predominantly caused by asbestos exposure. Due to nonspecific symptoms, PM is characterized by an advanced-stage diagnosis, resulting in a dismal prognosis. However, early diagnosis improves patient outcome. Currently, no diagnostic biomarkers or screening tools are available. Therefore, exhaled breath was explored as this can easily be obtained and contains volatile organic compounds, which are considered biomarkers for multiple (patho)physiological processes. A breath test, which differentiates asbestos-exposed (AEx) individuals from PM patients with 87% accuracy, was developed. However, before being implemented as a screening tool, the clinical utility of the test must be determined. Occupational AEx individuals underwent annual breath tests using multicapillary column/ion mobility spectrometry. A baseline breath test was taken and their individual risk of PM was estimated. PM patients were included as controls. In total, 112 AEx individuals and six PM patients were included in the first of four screening rounds. All six PM patients were correctly classified as having mesothelioma (100% sensitivity) and out of 112 AEx individuals 78 were classified by the breath-based model as PM patients (30% specificity). Given the large false positive outcome, the breath test will be repeated annually for three more consecutive years to adhere to the 'test, re-test' principle and improve the false positivity rate. A low-dose computed tomography scan in those with two consecutive positive tests will correlate test positives with radiological findings and the possible growth of a pleural tumor. Finally, the evaluation of the clinical value of a breath-based prediction model may lead to the initiation of a screening program for early detection of PM in Aex individuals, which is currently lacking. This clinical study received approval from the Antwerp University Hospital Ethics Committee (B300201837007).}, } @article {pmid37676382, year = {2024}, author = {Gabelloni, M and Faggioni, L and Brunese, MC and Picone, C and Fusco, R and Aquaro, GD and Cioni, D and Neri, E and Gandolfo, N and Giovagnoni, A and Granata, V}, title = {An overview on multimodal imaging for the diagnostic workup of pleural mesothelioma.}, journal = {Japanese journal of radiology}, volume = {42}, number = {1}, pages = {16-27}, pmid = {37676382}, issn = {1867-108X}, mesh = {Humans ; Neoplasm Staging ; *Mesothelioma/diagnostic imaging/etiology ; *Pleural Neoplasms/diagnostic imaging/pathology ; Risk Factors ; Multimodal Imaging ; }, abstract = {Pleural mesothelioma (PM) is an aggressive disease that has a strong causal relationship with asbestos exposure and represents a major challenge from both a diagnostic and therapeutic viewpoint. Despite recent improvements in patient care, PM typically carries a poor outcome, especially in advanced stages. Therefore, a timely and effective diagnosis taking advantage of currently available imaging techniques is essential to perform an accurate staging and dictate the most appropriate treatment strategy. Our aim is to provide a brief, but exhaustive and up-to-date overview of the role of multimodal medical imaging in the management of PM.}, } @article {pmid37673586, year = {2023}, author = {Eastwood, M and Marc, ST and Gao, X and Sailem, H and Offman, J and Karteris, E and Fernandez, AM and Jonigk, D and Cookson, W and Moffatt, M and Popat, S and Minhas, F and Robertus, JL}, title = {Malignant Mesothelioma subtyping via sampling driven multiple instance prediction on tissue image and cell morphology data.}, journal = {Artificial intelligence in medicine}, volume = {143}, number = {}, pages = {102628}, doi = {10.1016/j.artmed.2023.102628}, pmid = {37673586}, issn = {1873-2860}, support = {30731/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Humans ; *Mesothelioma, Malignant ; Neural Networks, Computer ; Recognition, Psychology ; }, abstract = {Malignant Mesothelioma is a difficult to diagnose and highly lethal cancer usually associated with asbestos exposure. It can be broadly classified into three subtypes: Epithelioid, Sarcomatoid, and a hybrid Biphasic subtype in which significant components of both of the previous subtypes are present. Early diagnosis and identification of the subtype informs treatment and can help improve patient outcome. However, the subtyping of malignant mesothelioma, and specifically the recognition of transitional features from routine histology slides has a high level of inter-observer variability. In this work, we propose an end-to-end multiple instance learning (MIL) approach for malignant mesothelioma subtyping. This uses an adaptive instance-based sampling scheme for training deep convolutional neural networks on bags of image patches that allows learning on a wider range of relevant instances compared to max or top-N based MIL approaches. We also investigate augmenting the instance representation to include aggregate cellular morphology features from cell segmentation. The proposed MIL approach enables identification of malignant mesothelial subtypes of specific tissue regions. From this a continuous characterisation of a sample according to predominance of sarcomatoid vs epithelioid regions is possible, thus avoiding the arbitrary and highly subjective categorisation by currently used subtypes. Instance scoring also enables studying tumor heterogeneity and identifying patterns associated with different subtypes. We have evaluated the proposed method on a dataset of 234 tissue micro-array cores with an AUROC of 0.89±0.05 for this task. The dataset and developed methodology is available for the community at: https://github.com/measty/PINS.}, } @article {pmid37667155, year = {2023}, author = {Yang, YX and Zhang, DK and Lu, HY and Zhao, XL and Yu, H}, title = {[Change trends and related risk factors of disease burden on mesothelioma in Jiangsu Province from 1990 to 2019].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {41}, number = {8}, pages = {594-600}, doi = {10.3760/cma.j.cn121094-20220815-00400}, pmid = {37667155}, issn = {1001-9391}, support = {H2017018//Medical Research Topic of Jiangsu Commission of Health/ ; }, mesh = {Female ; Male ; Humans ; *Mesothelioma/epidemiology ; *Mesothelioma, Malignant ; Risk Factors ; Cost of Illness ; *Occupational Exposure ; }, abstract = {Objective: To analyze the change trends and risk factors of mesothelioma disease burden in Jiangsu Province from 1990 to 2019. Methods: In January 2022, using the 2019 Global Burden of Disease Study Data, the Joinpoint regression model was used to analyze the change trends of incidence, mortality, disable-adjusted life years (DALY) and premature mortality of mesothelioma residents in Jiangsu Province from 1990 to 2019, and the attribution level of mesothelioma risk factors was estimated by population attributing fraction. Results: The standardized incidence rates of mesothelioma in Jiangsu Province from 1990 to 2019 ranged from 0.07/10(5) to 0.09/10(5), with an average annual percentage change (AAPC) of -1.1% (t=-13.56, P<0.001). AAPCs in males and females were -0.3% (t=-2.18, P=0.029) and -1.6% (t=-11.39, P<0.001), respectively. The standardized mortality rates of mesothelioma ranged from 0.07/10(5) to 0.09/10(5), the AAPC was -1.1% (t=-12.23, P<0.001), AAPC was -1.6% (t=-14.09, P<0.001) for females, and there was no significant change in males (t=-1.83, P=0.068). The premature mortality was 0.004%-0.006%, the AAPC was -1.0% (t=-4.40, P<0.001), AAPC was -1.7% (t=-13.72, P<0.001) for females, and there was no significant change in males (t=-0.68, P=0.495). The standardized DALY rates ranged from 1.86/10(5) to 2.32/10(5), the AAPC was -0.9% (t=-11.08, P<0.001), AAPC was -1.6% (t=-11.05, P<0.001) for females, and there was no significant change in males (t=-0.95, P=0.343). Both the standardized years of life lost (YLL) rate and the standardized years lived with disability (YLD) rate showed a decreasing trend, and the AAPCs were -0.9% (t=-7.66, P<0.001) and -1.0% (t=-12.88, P<0.001), respectively. The proportion of YLL in DALY was more than 98.5%. Among the risk factors for mesothelioma burden attribution, the AAPC attributed to occupational asbestos exposure of DALY was 1.4% (t=3.43, P=0.001). The AAPC of DALY rate of standardized attribution was -1.7% (t=-12.11, P<0.001) . Conclusion: The overall burden of mesothelioma in Jiangsu Province is decreasing, occupational asbestos exposure is still the main risk factor of mesothelioma in Jiangsu Province, and early diagnosis and treatment should be strengthened.}, } @article {pmid37664365, year = {2023}, author = {Sousa, B and Silva, J and Monteiro, N and Romano, M and Araújo, E}, title = {Malignant Peritoneal Mesothelioma: A Case Report.}, journal = {Cureus}, volume = {15}, number = {8}, pages = {e42902}, pmid = {37664365}, issn = {2168-8184}, abstract = {Malignant peritoneal mesothelioma (MPM) is a rare tumor of the serous membranes of the peritoneum and has been linked to exposure to asbestos and other risk factors. The clinical manifestations are vague, with a wide clinical spectrum, predominantly related to the abdominal involvement of the disease. Localized mesothelioma is an uncommon manifestation of the disease. Common symptoms include abdominal pain or abdominal distention, nausea, anorexia, and weight loss. Rarely, patients present with paraneoplastic syndrome. Due to the nonspecific symptoms, many patients already have advanced disease at the time of diagnosis. The authors report a case of a 75-year-old female patient who presented with symptoms of asthenia, anorexia, progressive paleness, and weight loss lasting five months. She reports later new-onset symptoms of diffuse abdominal pain and diarrhea associated with nausea. Laboratory tests showed anemia, mild leukocytosis, thrombocytosis, elevated C-reactive protein (CRP), and elevated liver enzymes. An abdominal and pelvic computed tomography (CT) scan revealed marked tissue thickening of an irregular and striated configuration of the leaflets and peritoneal reflections in an omental cake pattern, and a chest CT scan showed multiple bilateral pulmonary nodules, suggesting diffuse malignant disease. A CT-guided biopsy of a peritoneal implant was performed, establishing the diagnosis of malignant peritoneal mesothelioma. Due to rapid clinical deterioration, the patient did not receive any systemic treatment, surgery, or radiotherapy and was transitioned to comfort care. As in the presented case, most cases of MPM have diffuse peritoneal involvement at the time of diagnosis, although extra-abdominal involvement is very rare. This disease presentation is associated with high morbidity and mortality compared to cases of localized disease. There is no specific imaging diagnostic modality or valuable tumor markers for MPM. Although a CT scan remains important in the diagnostic approach, the changes found are not specific. Radiographically, MPM may present as mesenteric or parietal peritoneal nodules, visceral peritoneal thickening, ascites, or omental masses. Although these features may raise suspicion of MPM, a biopsy is necessary to confirm the diagnosis. Therefore, due to the rarity of this disease and its nonspecific signs or symptoms, MPM is difficult to diagnose, and the prognosis remains poor.}, } @article {pmid37658846, year = {2023}, author = {Qin, C and Xia, Q and Chen, ZJ and Zhou, Q and Zheng, X}, title = {En bloc resection of the recurrent pleural mesothelioma and reconstruction of the chest wall after immunotherapy: A case report.}, journal = {Thoracic cancer}, volume = {14}, number = {30}, pages = {3063-3066}, pmid = {37658846}, issn = {1759-7714}, mesh = {Female ; Humans ; Adult ; *Mesothelioma, Malignant/pathology ; *Thoracic Wall/surgery/pathology ; Nivolumab ; Ipilimumab ; *Mesothelioma/surgery/pathology ; *Pleural Neoplasms/surgery/pathology ; Immunotherapy ; }, abstract = {Malignant pleural mesothelioma (MPM) is associated with previous asbestos exposure, while more clinical insights into this disease have come from other case studies. Maximal cytoreduction is critical in disease control and might help to improve the prognosis. Here, a 41-year-old female presented with a 6-month history of a mass detected in the chest wall following resection of a right pleural mesothelioma 2 years previously. A fluorodeoxyglucose positron emission tomography/computed tomography scan showed a right chest wall mass with a blurred boundary 8.9 cm × 3.7 cm in size. The patient had received one cycle of bevacizumab, carboplatin, and pemetrexed, and two cycles of nivolumab, ipilimumab, and gemcitabine 5 months before admission. We subsequently resected the tumor, the involved diaphragm, and the fifth and sixth ribs, and titanium mesh and continuous suture were used to close the thoracic cage. The fixed paraffin-embedded tissues showed epithelioid pleural mesothelioma. The patient received nivolumab and ipilimumab postoperatively, and no recurrence was detected 16 months after surgery. En bloc resection with reconstructive surgery effectively removed the locally advanced malignancy and restored the biological function of the thorax with a favorable prognosis. Neoadjuvant immunotherapy might therefore be conducive to radical resection and perioperative immunotherapy might improve the prognosis.}, } @article {pmid37648326, year = {2023}, author = {Endo, I and Amatya, VJ and Kushitani, K and Kambara, T and Nakagiri, T and Aoe, K and Takeshima, Y}, title = {FOXM1 Promotes Mesothelioma Cell Migration and Invasion via Activation of SMAD Signaling.}, journal = {Anticancer research}, volume = {43}, number = {9}, pages = {3961-3968}, doi = {10.21873/anticanres.16583}, pmid = {37648326}, issn = {1791-7530}, mesh = {Humans ; *Mesothelioma/genetics ; *Mesothelioma, Malignant ; Carcinogenesis ; Cell Transformation, Neoplastic ; Cell Movement ; Forkhead Box Protein M1/genetics ; }, abstract = {BACKGROUND/AIM: Forkhead box M1 (FOXM1) is a transcription factor closely associated with various human malignancies and is considered an attractive target for cancer therapy. Mesothelioma is a malignancy primarily due to asbestos exposure and certain genetic factors, requiring a better understanding of tumorigenesis for improved treatment. Asbestos-exposed human mesothelial cells have been reported to up-regulate FOXM1 expression in a dose-dependent manner.

MATERIALS AND METHODS: FOXM1 expression was evaluated in mesothelioma tissues and cell lines. FOXM1 small interfering RNA was transfected into mesothelioma cell lines to analyze its biological functions and regulatory mechanisms.

RESULTS: FOXM1 was over-expressed in mesothelioma tissues and cell lines. Knock-down of FOXM1 in mesothelioma cell lines inhibited cell proliferation, migration, and invasion. These results suggest that up-regulation of FOXM1 expression promotes mesothelioma tumorigenesis and progression. We previously reported that insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) promotes the proliferation, migration, and invasion of mesothelioma cell lines. In this study, IGF2BP3 knock-down suppressed FOXM1 expression in mesothelioma cell lines. Our results suggest that IGF2BP3, an upstream regulator, contributes to increased FOXM1 expression. Furthermore, IGF2BP3 and FOXM1 knock-down suppressed SMAD signaling by inhibiting SMAD2/3 phosphorylation in mesothelioma cell lines.

CONCLUSION: IGF2BP3/FOXM1 promotes mesothelioma cell migration and invasion via SMAD signaling, highlighting IGF2BP3/FOXM1 as a potential target for mesothelioma treatment.}, } @article {pmid37642305, year = {2023}, author = {Zhang, C and Sun, Q and Zhao, J and Jiang, N and Hao, Y and Luo, J and Karim, S and Wu, L and de Perrot, M and Peng, C and Zhao, X}, title = {JSI-124 inhibits cell proliferation and tumor growth by inducing autophagy and apoptosis in murine malignant mesothelioma.}, journal = {Molecular carcinogenesis}, volume = {62}, number = {12}, pages = {1888-1901}, doi = {10.1002/mc.23623}, pmid = {37642305}, issn = {1098-2744}, support = {//Taishan Mountain Scholars of Shandong Province/ ; //Second hospital of Shandong University/ ; 2022YP104//Youth Talent Innovation Foundation of the Second Hospital of Shandong University/ ; //Special Construction Project Fund for Taishan Mountain Scholars of Shandong Province/ ; }, mesh = {Humans ; Animals ; Mice ; *Mesothelioma, Malignant ; Cell Line, Tumor ; Cell Proliferation ; Apoptosis ; Autophagy ; }, abstract = {Malignant pleural mesothelioma (MPM), mainly caused by asbestos exposure, has a poor prognosis and lacks effective treatment compared with other cancer types. The intracellular transcription factor signal transducer and activator of transcription 3 (STAT3) is overexpressed and hyperactivated in most human cancers. In this study, the role of STAT3 in murine MPM was examined. Inhibition of the Janus kinase 2 (JAK2)/STAT3 pathway with the selective inhibitor JSI-124 has an antitumor effect in murine MPM. Specifically, we demonstrated that JSI-124 inhibits murine MPM cell growth and induces apoptotic and autophagic cell death. Exposure of RN5 and AB12 cells to JSI-124 resulted in apoptosis via the Bcl-2 family of proteins. JSI-124 triggered autophagosome formation, accumulation, and conversion of LC3I to LC3II. Autophagy inhibitors, Chloroquine (CQ) and Bafilomycin A1 (Baf-A1), inhibited autophagy and sensitized RN5 and AB12 cells to JSI-124-induced apoptosis. Our data indicate that JSI-124 is a promising therapeutic agent for MPM treatment.}, } @article {pmid37637041, year = {2023}, author = {Deboever, N and Zhou, N and McGrail, DJ and Tomczak, K and Oliva, JL and Feldman, HA and Parra, E and Zhang, J and Lee, PP and Antonoff, MB and Hofstetter, WL and Mehran, RJ and Rajaram, R and Rice, DC and Roth, JA and Swisher, SS and Vaporciyan, AA and Altan, M and Weissferdt, A and Tsao, AS and Haymaker, CL and Sepesi, B}, title = {Radiographic response to neoadjuvant therapy in pleural mesothelioma should serve as a guide for patient selection for cytoreductive operations.}, journal = {Frontiers in oncology}, volume = {13}, number = {}, pages = {1216999}, pmid = {37637041}, issn = {2234-943X}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is associated with poor prognosis despite advances in multimodal therapeutic strategies. While patients with resectable disease may benefit from added survival with oncologic resection, patient selection for mesothelioma operations often relies on both objective and subjective evaluation metrics. We sought to evaluate factors associated with improved overall survival (OS) in patients with mesothelioma who underwent macroscopic complete resection (MCR).

METHODS: Patients with MPM who received neoadjuvant therapy and underwent MCR were identified in a prospectively maintained departmental database. Clinicopathologic, blood-based, and radiographic variables were collected and included in a Cox regression analysis (CRA). Response to neoadjuvant therapy was characterized by a change in tumor thickness from pretherapy to preoperative scans using the modified RECIST criteria.

RESULTS: In this study, 99 patients met the inclusion criteria. The median age of the included patients was 64.7 years, who were predominantly men, had smoking and asbestos exposure, and who received neoadjuvant therapy. The median change in tumor thickness following neoadjuvant therapy was -16.5% (interquartile range of -49.7% to +14.2%). CRA demonstrated reduced OS associated with non-epithelioid histology [hazard ratio (HR): 3.06, 95% confidence interval (CI): 1.62-5.78, p < 0.001] and a response to neoadjuvant therapy inferior to the median (HR: 2.70, CI: 1.55-4.72, p < 0.001). Patients who responded poorly (below median) to neoadjuvant therapy had lower median survival (15.8 months compared to 38.2 months, p < 0.001).

CONCLUSION: Poor response to neoadjuvant therapy in patients with MPM is associated with poor outcomes even following maximum surgical cytoreduction and should warrant a patient-centered discussion regarding goals of care and may therefore help guide further therapeutic decisions.}, } @article {pmid37628748, year = {2023}, author = {Ramundo, V and Zanirato, G and Palazzo, ML and Riganti, C and Aldieri, E}, title = {APE-1/Ref-1 Inhibition Blocks Malignant Pleural Mesothelioma Cell Proliferation and Migration: Crosstalk between Oxidative Stress and Epithelial Mesenchymal Transition (EMT) in Driving Carcinogenesis and Metastasis.}, journal = {International journal of molecular sciences}, volume = {24}, number = {16}, pages = {}, pmid = {37628748}, issn = {1422-0067}, support = {ALDE_RILO_19_01//University of Turin/ ; }, mesh = {Animals ; *Mesothelioma, Malignant ; Epithelial-Mesenchymal Transition ; Oxidative Stress ; Cell Proliferation ; Carcinogenesis ; Hyperplasia ; Endonucleases ; *Hominidae ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive cancer associated with asbestos exposure. MPM pathogenesis has been related both to oxidative stress, evoked by and in response to asbestos fibers exposure, and epithelial mesenchymal transition (EMT), an event induced by oxidative stress itself and related to cancer proliferation and metastasis. Asbestos-related primary oxidative damage is counteracted in the lungs by various redox-sensitive factors, often hyperactivated in some cancers. Among these redox-sensitive factors, Apurinic-apyrimidinic endonuclease 1 (APE-1)/Redox effector factor 1 (Ref-1) has been demonstrated to be overexpressed in MPM and lung cancer, but the molecular mechanism has not yet been fully understood. Moreover, asbestos exposure has been associated with induced EMT events, via some EMT transcription factors, such as Twist, Zeb-1 and Snail-1, in possible crosstalk with oxidative stress and inflammation events. To demonstrate this hypothesis, we inhibited/silenced Ref-1 in MPM cells; as a consequence, both EMT (Twist, Zeb-1 and Snail-1) markers and cellular migration/proliferation were significantly inhibited. Taken as a whole, these results show, for the first time, crosstalk between oxidative stress and EMT in MPM carcinogenesis and invasiveness, thus improving the knowledge to better address a preventive and therapeutic approach against this aggressive cancer.}, } @article {pmid37626858, year = {2023}, author = {Fiorilla, I and Martinotti, S and Todesco, AM and Bonsignore, G and Cavaletto, M and Patrone, M and Ranzato, E and Audrito, V}, title = {Chronic Inflammation, Oxidative Stress and Metabolic Plasticity: Three Players Driving the Pro-Tumorigenic Microenvironment in Malignant Mesothelioma.}, journal = {Cells}, volume = {12}, number = {16}, pages = {}, pmid = {37626858}, issn = {2073-4409}, mesh = {Humans ; *Mesothelioma, Malignant ; Reactive Oxygen Species ; Oxidative Stress ; Carcinogenesis ; Inflammation ; Tumor Microenvironment ; }, abstract = {Malignant pleural mesothelioma (MPM) is a lethal and rare cancer, even if its incidence has continuously increased all over the world. Asbestos exposure leads to the development of mesothelioma through multiple mechanisms, including chronic inflammation, oxidative stress with reactive oxygen species (ROS) generation, and persistent aberrant signaling. Together, these processes, over the years, force normal mesothelial cells' transformation. Chronic inflammation supported by "frustrated" macrophages exposed to asbestos fibers is also boosted by the release of pro-inflammatory cytokines, chemokines, growth factors, damage-associated molecular proteins (DAMPs), and the generation of ROS. In addition, the hypoxic microenvironment influences MPM and immune cells' features, leading to a significant rewiring of metabolism and phenotypic plasticity, thereby supporting tumor aggressiveness and modulating infiltrating immune cell responses. This review provides an overview of the complex tumor-host interactions within the MPM tumor microenvironment at different levels, i.e., soluble factors, metabolic crosstalk, and oxidative stress, and explains how these players supporting tumor transformation and progression may become potential and novel therapeutic targets in MPM.}, } @article {pmid37608979, year = {2023}, author = {Moitra, S and Tabrizi, AF and Khadour, F and Henderson, L and Melenka, L and Lacy, P}, title = {Exposure to insulating materials and risk of coronary artery diseases: a cross-sectional study.}, journal = {Frontiers in public health}, volume = {11}, number = {}, pages = {1235189}, pmid = {37608979}, issn = {2296-2565}, mesh = {Adult ; Male ; Humans ; Middle Aged ; Female ; *Coronary Artery Disease/epidemiology/etiology ; Cross-Sectional Studies ; *Heart Diseases ; Heart ; *Mesothelioma, Malignant ; }, abstract = {BACKGROUND: Although previous reports link exposure to insulating materials with an increased risk of mesothelioma and chronic respiratory diseases, studies evaluating their associations with the risk of coronary artery diseases (CAD) are lacking.

AIMS: We aimed at evaluating the associations between exposure to insulating materials and the 10-year risk of CAD among insulators.

METHODS: In this cross-sectional study, we recruited 643 adults (≥18 years), full-time insulators from the Local 110 Heat and Frost Insulators and Allied Workers Union in Edmonton, Alberta. We obtained demographic information, personal and family history, and job-exposure history, including experience (years) and types of exposure to insulating materials. Clinical profiling including Framingham risk scores (FRS) was assessed.

RESULTS: Of all insulators, 89% were men (mean ± SD age: 47 ± 12 years), 27% had a parental history of cardiac diseases, and 22% had a comorbid chronic respiratory disease. In total, 53% reported exposure to asbestos, while 61, 82, and 94% reported exposure to ceramic fibers, fiberglass, and mineral fibers, respectively. In single-exposure multivariable regression models adjusted for experience, marital status, and body mass index (BMI), asbestos was found to be associated with higher FRS (β: 1.004; 95%CI: 0.003-2.00). The association remained consistent in multi-exposure models and a higher association was found between asbestos exposure and FRS among insulators with comorbid chronic respiratory disease.

CONCLUSION: Our study demonstrates that apart from cancer and chronic respiratory diseases, asbestos exposure may also have a cardiac effect, thus warranting the need for systematic surveillance to protect workers from the adverse effects of these materials.}, } @article {pmid37605147, year = {2023}, author = {Welch, H and Harris, J and Pufulete, M and Dimagli, A and Benedetto, U and Maskell, N}, title = {Does previous asbestos exposure increase the risk of a post coronary artery bypass graft (CABG) pleural effusion - a routine data study?.}, journal = {BMC pulmonary medicine}, volume = {23}, number = {1}, pages = {307}, pmid = {37605147}, issn = {1471-2466}, mesh = {Humans ; *Asbestosis/epidemiology ; Prospective Studies ; *Pleural Effusion/epidemiology/etiology ; *Asbestos/adverse effects ; *Pleural Diseases/epidemiology/etiology ; Coronary Artery Bypass/adverse effects ; }, abstract = {BACKGROUND: Development of pleural effusion (PE) following CABG is common. Post-CABG PE are divided into early- (within 30 days of surgery) and delayed-onset (30 days-1 year) which are likely due to distinct pathological processes. Some experts suggest asbestos exposure may confer an independent risk for late-onset post-CABG PE, however no large studies have explored this potential association.

RESEARCH QUESTION: To explore possible association between asbestos exposure and post-CABG PE using routine data.

METHODS: All patients who underwent CABG 01/04/2013-31/03/2018 were identified from the Hospital Episode Statistics (HES) Database. This England-wide population was evaluated for evidence of asbestos exposure, pleural plaques or asbestosis and a diagnosis of PE or PE-related procedure from 30 days to 1 year post-CABG. Patients with evidence of PE three months prior to CABG were excluded, as were patients with a new mesothelioma diagnosis.

RESULTS: 68,150 patients were identified, of whom 1,003 (1%) were asbestos exposed and 2,377 (3%) developed late-onset PE. After adjusting for demographic data, Index of Multiple Deprivation and Charlson Co-morbidity Index, asbestos exposed patients had increased odds of PE diagnosis or related procedure such as thoracentesis or drainage (OR 1.35, 95% CI 1.03-1.76, p = 0.04). In those with evidence of PE requiring procedure alone, the adjusted OR was 1.66 (95% CI 1.14-2.40, p = 0.01). Additional subgroup analysis of the 518 patients coded for pleural plaques and asbestosis alone revealed an adjusted OR of post-CABG PE requiring a procedure of 2.16 (95% CI 1.38-3.37, p = 0.002).

INTERPRETATION: This large-scale study demonstrates prior asbestos exposure is associated with modestly increased risk of post-CABG PE development. The risk association appears higher in patients with assigned clinical codes indicative of radiological evidence of asbestos exposure (pleural plaques or asbestosis). This association may fit with a possible inflammatory co-pathogenesis, with asbestos exposure 'priming' the pleura resulting in greater propensity for PE evolution following the physiological insult of CABG surgery. Further work, including prospective studies and clinicopathological correlation are suggested to explore this further.}, } @article {pmid37571934, year = {2022}, author = {Nasirzadeh, N and Soltanpour, Z and Mohammadian, Y and Pourhasan, B}, title = {Lung Cancer and Pleural Mesothelioma Risk Assessment for the General Population Exposed to Asbestos in Different Regions of Tehran, Iran.}, journal = {Journal of research in health sciences}, volume = {22}, number = {4}, pages = {e00563}, pmid = {37571934}, issn = {2228-7809}, mesh = {Humans ; Iran/epidemiology ; Cross-Sectional Studies ; *Mesothelioma/epidemiology/etiology ; *Asbestos/toxicity ; *Lung Neoplasms/epidemiology/etiology ; *Pleural Neoplasms/epidemiology/etiology ; Risk Assessment ; *Occupational Exposure/adverse effects/analysis ; }, abstract = {BACKGROUND: Asbestos is a natural fiber leading to health risks like chronic lung diseases. The current study aimed to estimate pleural mesothelioma and lung cancer risk for population exposure to asbestos in Tehran, Iran.

STUDY DESIGN: A cross-sectional study.

METHODS: According to the annual report of Air Quality Control Company (AQCC), from 2011-2020, carcinogenic risk and mesothelioma were assessed based on the Environmental Protection Agency (EPA) method using the Monte Carlo simulation (MCS). The relative risk (RR) of mortality cancer was calculated based on Camus and colleagues' model. Moreover, mesothelioma risk was estimated by Bourgault and colleagues' model.

RESULTS: The mean concentration and health risk of asbestos in ambient air generally reduced from 2011 to 2020. The highest mortality risk for lung cancer was 8.4 per 100000 persons in 2011 and reduced to 1.8 in 2017. For mesothelioma, the corresponding values were 8.96 per 100000 persons in 2011 and reduced to 1.92 in 2017.

CONCLUSION: The findings of this study could be helpful to health policymakers in the management of asbestos risk.}, } @article {pmid37567753, year = {2023}, author = {Stella, S and Consonni, D and Migliore, E and Stura, A and Cavone, D and Vimercati, L and Miligi, L and Piro, S and Landi, MT and Caporaso, NE and Curti, S and Mattioli, S and Brandi, G and Gioscia, C and Eccher, S and Murano, S and Casotto, V and Comiati, V and Negro, C and D'Agostin, F and Genova, C and Benfatto, L and Romanelli, A and Grappasonni, I and Madeo, G and Cozzi, I and Romeo, E and Tommaso, S and Carrozza, F and Labianca, M and Tallarigo, F and Cascone, G and Melis, M and Marinaccio, A and Binazzi, A and Mensi, C and , }, title = {Pleural mesothelioma risk in the construction industry: a case-control study in Italy, 2000-2018.}, journal = {BMJ open}, volume = {13}, number = {8}, pages = {e073480}, pmid = {37567753}, issn = {2044-6055}, mesh = {Humans ; Male ; *Construction Industry ; Case-Control Studies ; *Occupational Exposure/adverse effects ; *Occupational Diseases/epidemiology ; *Mesothelioma/epidemiology/etiology ; *Mesothelioma, Malignant ; *Asbestos/adverse effects ; *Pleural Neoplasms/epidemiology/etiology ; Logistic Models ; Italy/epidemiology ; }, abstract = {OBJECTIVES: Workers in the construction industry have been exposed to asbestos in various occupations. In Italy, a National Mesothelioma Registry has been implemented more than 20 years ago. Using cases selected from this registry and exploiting existing control data sets, we estimated relative risks for pleural mesothelioma (PM) among construction workers.

DESIGN: Case-control study.

SETTING: Cases from the National Mesothelioma Registry (2000-2018), controls from three previous case-control studies.

METHODS: We selected male PM incident cases diagnosed in 2000-2018. Population controls were taken from three studies performed in six Italian regions within two periods (2002-2004 and 2012-2016). Age-adjusted and period-adjusted unconditional logistic regression models were fitted to estimate odds ratios (OR) for occupations in the construction industry. We followed two approaches, one (primary) excluding and the other (secondary) including subjects employed in other non-construction blue collar occupations for >5 years. For both approaches, we performed an overall analysis including all cases and, given the incomplete temporal and geographic overlap of cases and controls, three time or/and space restricted sensitivity analyses.

RESULTS: The whole data set included 15 592 cases and 2210 controls. With the primary approach (4797 cases and 1085 controls), OR was 3.64 (2181 cases) for subjects ever employed in construction. We found elevated risks for blue-collar occupations (1993 cases, OR 4.52), including bricklayers (988 cases, OR 7.05), general construction workers (320 cases, OR 4.66), plumbers and pipe fitters (305 cases, OR 9.13), painters (104 cases, OR 2.17) and several others. Sensitivity analyses yielded very similar findings. Using the secondary approach, we observed similar patterns, but ORs were remarkably lower.

CONCLUSIONS: We found markedly increased PM risks for most occupations in the construction industry. These findings are relevant for compensation of subjects affected with mesothelioma in the construction industry.}, } @article {pmid37553196, year = {2023}, author = {Ferguson, K and Neilson, M and Mercer, R and King, J and Marshall, K and Welch, H and Tsim, S and Maskell, NA and Rahman, NM and Evison, M and Blyth, KG}, title = {Results of the Meso-ORIGINS feasibility study regarding collection of matched benign-mesothelioma tissue pairs by longitudinal surveillance.}, journal = {BMJ open}, volume = {13}, number = {8}, pages = {e067780}, pmid = {37553196}, issn = {2044-6055}, support = {29372/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Humans ; Feasibility Studies ; Prospective Studies ; Retrospective Studies ; *Mesothelioma, Malignant ; *Mesothelioma/pathology ; *Pleural Neoplasms/epidemiology ; *Asbestos ; *Lung Neoplasms/pathology ; }, abstract = {OBJECTIVES: To assess key elements of the design for Meso-ORIGINS (Mesothelioma Observational study of RIsk prediction and Generation of paired benign-meso tissue samples, Including a Nested MRI Substudy), an ambitious, UK-wide, prospective study that will collect ≥63 matched benign-mesothelioma tissue pairs through longitudinal surveillance and repeat biopsy of patients with asbestos-associated pleural inflammation (AAPI).

DESIGN: A multicentre, mixed-methods feasibility study, comprising a prospective observational element, evaluating recruitment feasibility, technical feasibility of repeat local anaesthetic thoracoscopy (LAT) and patient acceptability, and a retrospective cohort study focused on AAPI-mesothelioma evolution rate, informing sample size.

SETTING: 4 UK pleural disease centres (February 2019-January 2020).

PARTICIPANTS: Patients with AAPI (history or typical imaging plus appropriate pleural histology) were eligible for both elements. In August 2019, eligibility for the prospective element was broadened, including addition of radiological AAPI for technical feasibility and patient acceptability endpoints only. Retrospective cases required ≥2 years follow-up.

OUTCOME MEASURES: A prospective recruitment target was set a priori at 27 histological AAPI cases (or 14 in any 6 months). Technical feasibility and patient acceptability were determined at 6-month follow-up by thoracic ultrasound surrogates and questionnaires, respectively. Retrospective malignant pleural mesothelioma evolution rate was defined by proportion (95% CI). Baseline predictors of evolution were identified using logistic regression.

RESULTS: 296 patients with AAPI (39 prospective, 257 retrospective) were recruited/selected. 21/39 prospective recruits were histologically diagnosed (target n=27). Repeat LAT was technically feasible and acceptable in 13/28 (46%) and 24/36 (67%) cases with complete follow-up data. Mesothelioma evolution was confirmed histologically in 36/257 retrospective cases (14% (95% CI 10.3% to 18.8%)) and associated with malignant CT features (OR 4.78 (95% CI 2.36 to 9.86)) and age (OR 1.06 (95% CI 1.02 to 1.12)).

CONCLUSIONS: Our initial eligibility criteria were too narrow. Meso-ORIGINS will recruit a broader cohort, including prevalent cases, any biopsy type and patients with malignant CT features. A range of rebiopsy techniques will be allowed, accounting for technical and patient factors. The sample size has been reduced to 500.

TRIAL REGISTRATION NUMBER: ISRCTN12840870.}, } @article {pmid37547483, year = {2023}, author = {Damiran, N and Frank, AL}, title = {Mongolia: Failure of Total Banning of Asbestos.}, journal = {Annals of global health}, volume = {89}, number = {1}, pages = {50}, pmid = {37547483}, issn = {2214-9996}, mesh = {Humans ; Mongolia ; *Occupational Exposure/adverse effects/prevention & control/analysis ; *Asbestos/toxicity ; *Mesothelioma/epidemiology/prevention & control ; *Mesothelioma, Malignant ; *Lung Neoplasms ; }, abstract = {The primary uses of asbestos in Mongolia are in thermal power plants, construction and at railway companies. There is, however, limited data on both asbestos consumption and asbestos related disease (ARD) in Mongolia. The purpose of this paper is to report on the failure to completely ban asbestos in Mongolia. To write this paper, available asbestos related literature, published nationally and internationally, and legal regulations, national standards and guidelines on asbestos control were reviewed. Mongolia consumed a total of 44,421.9 metric tons of asbestos containing materials (AMCs) between 1996 and 2014. As a key indicator of ARD, 54 cases of mesothelioma were diagnosed at the National Cancer Center by pathological testing of tissue samples between 1994 and 2013. In 2010, The government made the decision to stop all types of asbestos use under the Law on Toxic and Hazardous Substances. However, there was no nationwide action plan to gradually reduce asbestos use, promote substitutes and raise awareness of health hazards and economic burdens in the future from asbestos use. There was also no planning for safe removal of asbestos currently in place. After the banning of asbestos, thermal power plants told the government that they could not produce electricity without insulation of AMCs and substitution materials were economically not feasible. Due to pressure from the energy sector and inadequate awareness of asbestos hazards, the government changed the legal status on asbestos in 2011 as a restricted chemical. Asbestos is still allowed to be used, and workers and the general community are still unnecessarily exposed to this carcinogen.}, } @article {pmid37529811, year = {2023}, author = {Kuramochi, M and Muraoka, T and Shinonaga, M and Ohtani, H and Kuraoka, S}, title = {Malignant Pleural Mesothelioma (MPM) Presenting as Hydropneumothorax.}, journal = {Cureus}, volume = {15}, number = {7}, pages = {e41243}, pmid = {37529811}, issn = {2168-8184}, abstract = {An 86-year-old man presented with bilateral lower limb edema and was found to have hydropneumothorax on chest radiography. CT revealed a substantial pleural effusion and plaques. The patient had a history of working in a stone workshop, but the extent of asbestos exposure remained unknown. Thoracic drainage and subsequent thoracoscopic surgery confirmed the presence of biphasic malignant mesothelioma through pathological examination. Hydropneumothorax as a presentation of malignant pleural mesothelioma (MPM) is rare, with only a few similar cases reported. Remarkably, despite the coexistence of plural effusion and pneumothorax, the patient did not experience dyspnea. The examination also revealed tumor rupture and disruption of the pleura. Considering the possibility of MPM in patients with asymptomatic hydropneumothorax is essential for early diagnosis and appropriate management.}, } @article {pmid37528762, year = {2023}, author = {Frank, AL}, title = {Four mesothelioma cases from a single automotive dealership: A case series.}, journal = {American journal of industrial medicine}, volume = {66}, number = {10}, pages = {904-906}, doi = {10.1002/ajim.23521}, pmid = {37528762}, issn = {1097-0274}, mesh = {Humans ; Asbestos, Serpentine ; *Lung Neoplasms/etiology ; *Mesothelioma/etiology ; *Asbestos ; *Mesothelioma, Malignant ; *Occupational Exposure/adverse effects ; }, abstract = {BACKGROUND: Four cases of mesothelioma were noted in a workplace of some 110 persons at a tractor dealership between 2006 and 2023. Each worker had a different job title.

METHODS: Medical-legal case material was reviewed and abstracted from four cases from the same dealership, all supplied via one law firm.

RESULTS: Four mesotheliomas are reported from this single facility that used chrysotile asbestos automotive products. Two of the four cases had no other known exposures to asbestos.

DISCUSSION: Automotive products containing chrysotile do appear capable of causing mesothelioma. Job category is not a good surrogate for exposure.}, } @article {pmid37524680, year = {2023}, author = {Zhang, GZ and Zheng, GQ and Wei, F and Liu, YY and Song, H and Liang, YF}, title = {[Pathological classification of malignant peritoneal mesothelioma and comparative analysis with peritoneal carcinomatosis].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {41}, number = {7}, pages = {541-546}, doi = {10.3760/cma.j.cn121094-20211203-00597}, pmid = {37524680}, issn = {1001-9391}, abstract = {Objective: To analyze the pathological classification of malignant peritoneal mesothelioma (MPeM) and screen the immunohistochemical markers that can distinguish MPeM from peritoneal metastatic carcinoma (PC) . Methods: In June 2020, the pathological results of peritoneal biopsy of 158 MPeM and 138 PC patients from Cangzhou Central Hospital, Cangzhou People's Hospital, and Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine from May 2011 to July 2019 were retrospectively analyzed, and the pathological classifications of MPeM in Cangzhou were summarized. Immunohistochemical markers of MPeM and PC patients were analyzed, and receiver operating characteristic curve (ROC curve) was drawn for differential diagnosis of MPeM and PC. Results: There were 55 male and 103 female MPeM patients in Cangzhou, with an average age of 57.1 years old. The asbestos exposure rate was 91.14% (144/158). The most common pathological classifications were cutaneous type, accounting for 90.51% (143/158). There were significant differences in the expression of calreticulum protein, CK5/6, vimentin, D2-40, carcinoembryonic antigen (CEA) and tail type homologous nuclear gene transcription factor 2 (CDX-2) between MPeM and PC (P<0.05). Among the 6 positive markers, the sensitivity of calreticulum protein was the highest (0.905) and CEA was the lowest (0.428) . Conclusion: Calreticulum protein, CK5/6, vimentin, D2-40, CEA and CDX-2 may be used as specific markers to distinguish the diagnosis of MPeM from PC.}, } @article {pmid37517251, year = {2023}, author = {Rouabeh, W and Cherif, T and Mgarrech, I and Ajmi, N and Kortas, C and Jerbi, S}, title = {Case report and analysis of the literature on sarcomatous mesothelioma of the left atrium.}, journal = {International journal of surgery case reports}, volume = {109}, number = {}, pages = {108537}, pmid = {37517251}, issn = {2210-2612}, abstract = {INTRODUCTION AND IMPORTANCE: Primary intracardiac malignant mesothelioma is an extremely uncommon condition with a terrible prognosis. Because of its rarity, there have been extremely few examples described in the literature.

CASE PRESENTATION: We are reporting the instance of a 44-year-old lady who was referred to the department of cardiology for worsening dyspnea, palpitations, and a recent syncopal episode. On examination, the patient had signs of global heart failure. Cardiac imaging showed a tissue mass infiltrating the atrioventricular sulcus at the mitral valve level, responsible for severe mitral stenosis. Pleural effusion without an intrapleural mass was also noted. Urgent surgery was performed, including excision of the tumor mass, mechanical replacement of the mitral valve, and tricuspid plasty. The anatomo-pathological study concluded in cardiac mesothelioma. The patient was transferred back to the cardiology department 9 months after surgery due to severe left heart failure. TTE and TOE were performed and revealed tumor recurrence responsible for severe mitral stenosis. The course was marked by the onset of cardiogenic shock refractory to treatment, followed by the death of the patient. The case we are reporting seems to be the initial instance documented as exclusively primary intracardiac mesothelioma especially its lack of association with any other pleural sarcomatoid mesothelioma or asbestos exposure.

CLINICAL DISCUSSION: In cases where a large atrial tumor is present, prompt surgical intervention is recommended to mitigate the risk of catastrophic embolization or valve orifice obstruction. The objective of surgical intervention is to excise the entire neoplasm with sufficient surrounding tissue, a feat that is infrequently achievable. Palliative debulking may be a beneficial intervention for patients who do not necessitate complete resection, particularly those experiencing relevant or rapidly escalating symptoms. Cardiac transplantation remains a viable option in the event of an unresectable malignant tumor.

CONCLUSION: The short-term prognosis is poor. Surgical treatment remains the best treatment for this type of tumor. Total excision should be considered, but may not be feasible in all cases. Adjuvant chemotherapy may be considered.}, } @article {pmid37483507, year = {2023}, author = {Wang, J and Huang, X and Ma, R and Zhang, Q and Wu, N and Du, X and Ye, Q}, title = {The incidence of malignancies in asbestosis with chrysotile exposure: a large Chinese prospective cohort study.}, journal = {Frontiers in oncology}, volume = {13}, number = {}, pages = {1172496}, pmid = {37483507}, issn = {2234-943X}, abstract = {BACKGROUND: Asbestos exposure is closely related to the occurrence and development of various malignancies. This prospective cohort study aimed to evaluate the incidence rate and potential risk factors in a cohort of asbestosis patients in China.

METHODS: The incidence of malignancies was determined in patients who had been exposed to chrysotile asbestos and diagnosed with asbestosis sequentially at Beijing Chaoyang Hospital from 1 January 2007 to 31 December 2019. Cox regression analyses were used to analyze the correlations between clinical variables and asbestosis combined with malignancies.

RESULTS: A total of 618 patients with asbestosis were identified, of whom 544 were eligible for analysis. Among them, 89 (16.36%) were diagnosed with various malignancies. The standardized incidence ratios (SIRs) of patients with asbestosis combined with malignancies were 16.61, 175, 5.23, and 8.77 for lung cancer, mesothelioma, breast cancer, and endometrial carcinoma, respectively. The risks of all malignancies and lung cancer increased with initial exposure before 17 years old, longer asbestos exposure, and smoking.

CONCLUSIONS: The SIRs of patients with asbestosis-related malignancies were significantly increased in lung cancer, mesothelioma, breast cancer, and endometrial carcinoma in a hospital-based Chinese cohort. Smoking and the duration of asbestos exposure increased the risk of lung cancer.}, } @article {pmid37476375, year = {2023}, author = {Shi, H and Zhang, L and Yu, TK and Zhuang, L and Ke, H and Johnson, B and Rath, E and Lee, K and Klebe, S and Kao, S and Qin, KL and Pham, HNT and Vuong, Q and Cheng, YY}, title = {Leptospermum extract (QV0) suppresses pleural mesothelioma tumor growth in vitro and in vivo by mitochondrial dysfunction associated apoptosis.}, journal = {Frontiers in oncology}, volume = {13}, number = {}, pages = {1162027}, pmid = {37476375}, issn = {2234-943X}, abstract = {Pleural mesothelioma (PM) is a highly aggressive, fast-growing asbestos-induced cancer with limited effective treatments. There has been interest in using naturally occurring anticancer agents derived from plant materials for the treatment of PM. However, it is unclear if an aqueous extract from Leptospermum polygalifolium (QV0) has activity against PM. Here we investigated the anti-cancer properties of QV0 and Defender[®] (QV0 dietary formula) in vitro and in vivo, respectively. QV0 suppressed the growth of eight PM cell lines in a dose-dependent manner, effective at concentrations as low as 0.02% w/v (equivalent to 0.2 mg/ml). This response was found to be associated with inhibited cell migration, proliferation, and colony formation but without evident cell cycle alteration. We observed mitochondrial dysfunction post-QV0 treatment, as evidenced by significantly decreased basal and maximal oxygen consumption rates. Ten SCID mice were treated with 0.25 mg/g Defender[®] daily and exhibited reduced tumor size over 30 days, which was associated with an average extension of seven days of mouse life. There was no evidence of liver toxicity or increased blood glucose post-treatment in animals treated with Defender[®]. Significantly enhanced tumor apoptosis was observed in the Defender[®]-treated animals, correlating to mitochondrial dysfunction. Lastly, the high levels of polyphenols and antioxidant properties of QV0 and Defender[®] were detected in HPLC analysis. To the best of our knowledge, this study constitutes the first demonstration of an improved host survival (without adverse effects) response in a QV0-treated PM mouse model, associated with evident inhibition of PM cell growth and mitochondrial dysfunction-related enhancement of tumor apoptosis.}, } @article {pmid37469419, year = {2023}, author = {Sahu, RK and Ruhi, S and Jeppu, AK and Al-Goshae, HA and Syed, A and Nagdev, S and Widyowati, R and Ekasari, W and Khan, J and Bhattacharjee, B and Goyal, M and Bhattacharya, S and Jangde, RK}, title = {Malignant mesothelioma tumours: molecular pathogenesis, diagnosis, and therapies accompanying clinical studies.}, journal = {Frontiers in oncology}, volume = {13}, number = {}, pages = {1204722}, pmid = {37469419}, issn = {2234-943X}, abstract = {The pathetic malignant mesothelioma (MM) is a extremely uncommon and confrontational tumor that evolves in the mesothelium layer of the pleural cavities (inner lining- visceral pleura and outer lining- parietal pleura), peritoneum, pericardium, and tunica vaginalis and is highly resistant to standard treatments. In mesothelioma, the predominant pattern of lesions is a loss of genes that limit tumour growth. Despite the worldwide ban on the manufacture and supply of asbestos, the prevalence of mesothelioma continues to increase. Mesothelioma presents and behaves in a variety of ways, making diagnosis challenging. Most treatments available today for MM are ineffective, and the median life expectancy is between 10 and 12 months. However, in recent years, considerable progress has already been made in understanding the genetics and molecular pathophysiology of mesothelioma by addressing hippo signaling pathway. The development and progression of MM are related to many important genetic alterations. This is related to NF2 and/or LATS2 mutations that activate the transcriptional coactivator YAP. The X-rays, CT scans, MRIs, and PET scans are used to diagnose the MM. The MM are treated with surgery, chemotherapy, first-line combination chemotherapy, second-line treatment, radiation therapy, adoptive T-cell treatment, targeted therapy, and cancer vaccines. Recent clinical trials investigating the function of surgery have led to the development of innovative approaches to the treatment of associated pleural effusions as well as the introduction of targeted medications. An interdisciplinary collaborative approach is needed for the effective care of persons who have mesothelioma because of the rising intricacy of mesothelioma treatment. This article highlights the key findings in the molecular pathogenesis of mesothelioma, diagnosis with special emphasis on the management of mesothelioma.}, } @article {pmid37466108, year = {2023}, author = {Lombardo, C and Broggi, G and Vitale, E and Ledda, C and Loreto, C and Matera, S and Hagnas, M and Caltabiano, R and Filetti, V}, title = {Expression of stathmin in asbestos-like fibers-induced mesothelioma: A preliminary report.}, journal = {Histology and histopathology}, volume = {38}, number = {11}, pages = {1249-1256}, pmid = {37466108}, issn = {1699-5848}, support = {2020/2022//Interdepartment "PIA.CE.RI" Research Plan of University of Catania/ ; }, mesh = {Humans ; *Asbestos/toxicity/analysis ; Biomarkers/analysis ; *Lung Neoplasms/pathology ; *Mesothelioma/diagnosis/metabolism ; *Mesothelioma, Malignant ; Sicily ; Stathmin ; }, abstract = {BACKGROUND: Mesothelioma is strongly associated with exposure to asbestos fibers, however, recent studies have also linked exposure to "naturally occurring asbestos" fibers with this disease. Fluoro-edenite, a silicate mineral found in the southeast of Biancavilla (Sicily, Italy), has been identified as a potential risk factor for mesothelioma. Unfortunately, this cancer often has a poor prognosis, and current diagnostic and prognostic biomarkers are inadequate. Histological subtype, gender, and age at diagnosis are the most significant parameters for mesothelioma. Stathmin, a cytosolic protein that regulates cell growth and migration and is overexpressed in many human malignancies, has not yet been linked to mesothelioma survival or clinical-pathological variables.

AIM: The aim of this study was to investigate the immunohistochemical expression of stathmin in ten mesothelioma tissue samples with available clinical and follow-up data.

MATERIAL AND METHODS: Paraffin-embedded tissue samples from ten mesothelioma patients were processed for immunohistochemical analyses to evaluate stathmin expression.

RESULTS: Our findings suggest that stathmin overexpression is associated with shorter overall survival in patients with mesothelioma. Furthermore, stathmin expression was significantly correlated with the survival time of mesothelioma patients.

CONCLUSION: Our results suggest that stathmin expression may serve as a potential prognostic biomarker for mesothelioma. This biomarker could be used to promptly identify patients with poor prognosis and to guide clinicians in the selection of treatment options.}, } @article {pmid37460925, year = {2023}, author = {Torricelli, F and Donati, B and Reggiani, F and Manicardi, V and Piana, S and Valli, R and Lococo, F and Ciarrocchi, A}, title = {Spatially resolved, high-dimensional transcriptomics sorts out the evolution of biphasic malignant pleural mesothelioma: new paradigms for immunotherapy.}, journal = {Molecular cancer}, volume = {22}, number = {1}, pages = {114}, pmid = {37460925}, issn = {1476-4598}, mesh = {Humans ; *Mesothelioma, Malignant ; *Mesothelioma/genetics/therapy ; Transcriptome ; Ecosystem ; *Pleural Neoplasms/genetics/therapy ; *Lung Neoplasms/genetics ; Prognosis ; Biomarkers, Tumor/genetics ; Immunotherapy ; }, abstract = {BACKGROUND: Malignant Pleural Mesothelioma (MPM) is a dreadful disease escaping the classical genetic model of cancer evolution and characterized by wide heterogeneity and transcriptional plasticity. Clinical evolution of MPM is marked by a progressive transdifferentiation that converts well differentiated epithelioid (E) cells into undifferentiated and pleomorphic sarcomatoid (S) phenotypes. Catching the way this transition takes place is necessary to understand how MPM develops and progresses and it is mandatory to improve patients' management and life expectancy. Bulk transcriptomic approaches, while providing a significant overview, failed to resolve the timing of this evolution and to identify the hierarchy of molecular events through which this transition takes place.

METHODS: We applied a spatially resolved, high-dimensional transcriptomic approach to study MPM morphological evolution. 139 regions across 8 biphasic MPMs (B-MPMs) were profiled using the GeoMx™Digital Spatial Profiler to reconstruct the positional context of transcriptional activities and the spatial topology of MPM cells interactions. Validation was conducted on an independent large cohort of 84 MPMs by targeted digital barcoding analysis.

RESULTS: Our results demonstrated the existence of a complex circular ecosystem in which, within a strong asbestos-driven inflammatory environment, MPM and immune cells affect each other to support S-transdifferentiation. We also showed that TGFB1 polarized M2-Tumor Associated Macrophages foster immune evasion and that TGFB1 expression correlates with reduced survival probability.

CONCLUSIONS: Besides providing crucial insights into the multidimensional interactions governing MPM clinical evolution, these results open new perspectives to improve the use of immunotherapy in this disease.}, } @article {pmid37441092, year = {2023}, author = {Farahmand, P and Gyuraszova, K and Rooney, C and Raffo-Iraolagoitia, XL and Jayasekera, G and Hedley, A and Johnson, E and Chernova, T and Malviya, G and Hall, H and Monteverde, T and Blyth, K and Duffin, R and Carlin, LM and Lewis, D and Le Quesne, J and MacFarlane, M and Murphy, DJ}, title = {Asbestos accelerates disease onset in a genetic model of malignant pleural mesothelioma.}, journal = {Frontiers in toxicology}, volume = {5}, number = {}, pages = {1200650}, pmid = {37441092}, issn = {2673-3080}, support = {23983/CRUK_/Cancer Research UK/United Kingdom ; 25006/CRUK_/Cancer Research UK/United Kingdom ; MC_UU_00025/5/MRC_/Medical Research Council/United Kingdom ; }, abstract = {Hypothesis: Asbestos-driven inflammation contributes to malignant pleural mesothelioma beyond the acquisition of rate-limiting mutations. Methods: Genetically modified conditional allelic mice that were previously shown to develop mesothelioma in the absence of exposure to asbestos were induced with lentiviral vector expressing Cre recombinase with and without intrapleural injection of amosite asbestos and monitored until symptoms required euthanasia. Resulting tumours were examined histologically and by immunohistochemistry for expression of lineage markers and immune cell infiltration. Results: Injection of asbestos dramatically accelerated disease onset and end-stage tumour burden. Tumours developed in the presence of asbestos showed increased macrophage infiltration. Pharmacological suppression of macrophages in mice with established tumours failed to extend survival or to enhance response to chemotherapy. Conclusion: Asbestos-driven inflammation contributes to the severity of mesothelioma beyond the acquisition of rate-limiting mutations, however, targeted suppression of macrophages in established epithelioid mesothelioma showed no therapeutic benefit.}, } @article {pmid37421230, year = {2024}, author = {Jama, M and Zhang, M and Poile, C and Nakas, A and Sharkey, A and Dzialo, J and Dawson, A and Kutywayo, K and Fennell, DA and Hollox, EJ}, title = {Gene fusions during the early evolution of mesothelioma correlate with impaired DNA repair and Hippo pathways.}, journal = {Genes, chromosomes & cancer}, volume = {63}, number = {1}, pages = {e23189}, doi = {10.1002/gcc.23189}, pmid = {37421230}, issn = {1098-2264}, support = {//British Lung Foundation/ ; //Mesothelioma UK/ ; }, mesh = {Humans ; *Mesothelioma, Malignant/genetics ; Hippo Signaling Pathway ; *Lung Neoplasms/genetics/pathology ; *Mesothelioma/genetics ; *Asbestos ; DNA Repair/genetics ; Gene Fusion ; }, abstract = {Malignant pleural mesothelioma (MPM), a rare cancer a long latency period (up to 40 years) between asbestos exposure and disease presentation. The mechanisms coupling asbestos to recurrent somatic alterations are poorly defined. Gene fusions arising through genomic instability may create novel drivers during early MPM evolution. We explored the gene fusions that occurred early in the evolutionary history of the tumor. We conducted multiregional whole exome sequencing (WES) of 106 samples from 20 patients undergoing pleurectomy decortication and identified 24 clonal nonrecurrent gene fusions, three of which were novel (FMO9P-OR2W5, GBA3, and SP9). The number of early gene fusion events detected varied from zero to eight per tumor, and presence of gene fusions was associated with clonal losses involving the Hippo pathway genes and homologous recombination DNA repair genes. Fusions involved known tumor suppressors BAP1, MTAP, and LRP1B, and a clonal oncogenic fusion involving CACNA1D-ERC2, PARD3B-NT5DC2, and STAB2-NT5DC2 fusions were also identified as clonal fusions. Gene fusions events occur early during MPM evolution. Individual fusions are rare as no recurrent truncal fusions event were found. This suggests the importance of early disruption of these pathways in generating genomic rearrangements resulting in potentially oncogenic gene fusions.}, } @article {pmid37399948, year = {2023}, author = {Coccè, V and Bonelli, M and La Monica, S and Alfieri, R and Doneda, L and Martegani, E and Alessandri, G and Lagrasta, CA and Giannì, A and Sordi, V and Petrella, F and Roncoroni, L and Paino, F and Pessina, A}, title = {Mesenchymal stromal cells loaded with Paclitaxel (PacliMES) a potential new therapeutic approach on mesothelioma.}, journal = {Biochemical pharmacology}, volume = {214}, number = {}, pages = {115678}, doi = {10.1016/j.bcp.2023.115678}, pmid = {37399948}, issn = {1873-2968}, mesh = {Humans ; Paclitaxel ; *Mesothelioma, Malignant ; Cell Line, Tumor ; *Mesothelioma/drug therapy ; *Mesenchymal Stem Cells ; }, abstract = {Malignant pleural mesothelioma is an asbestos-related tumor originating in mesothelial cells of the pleura that poorly responds to chemotherapeutic approaches. Adult mesenchymal stromal cells derived either from bone marrow or from adipose tissue may be considered a good model for cell-based therapy, a treatment which has experienced significant interest in recent years. The present study confirms that Paclitaxel is effective on mesothelioma cell proliferation in 2D and 3D in vitro cultures, and that 80,000 mesenchymal stromal cells loaded with Paclitaxel inhibit tumor growth at a higher extent than Paclitaxel alone. An in vivo approach to treat in situ mesothelioma xenografts using a minimal amount of 10[6] mesenchymal stromal cells loaded with Paclitaxel showed the same efficacy of a systemic administration of 10 mg/kg of Paclitaxel. These data strongly support drug delivery system by mesenchymal stromal cells as a useful approach against many solid tumors. We look with interest at the favourable opinion recently expressed by the Italian Drug Agency on the procedure for the preparation of mesenchymal stromal cells loaded with Paclitaxel in large-scale bioreactor systems and their storage until clinical use. This new Advanced Medicinal Therapy Product, already approved for a Phase I clinical trial on mesothelioma patients, could pave the way for mesenchymal stromal cells use as drug delivery system on other solid tumors for adjuvant therapy associated with surgery and radiotherapy.}, } @article {pmid37398648, year = {2023}, author = {Digifico, E and Erreni, M and Mannarino, L and Marchini, S and Ummarino, A and Anfray, C and Bertola, L and Recordati, C and Pistillo, D and Roncalli, M and Bossi, P and Zucali, PA and D'Incalci, M and Belgiovine, C and Allavena, P}, title = {Important functional role of the protein osteopontin in the progression of malignant pleural mesothelioma.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1116430}, pmid = {37398648}, issn = {1664-3224}, mesh = {Animals ; Humans ; Mice ; Cytokines/therapeutic use ; *Mesothelioma/drug therapy ; *Mesothelioma, Malignant ; *Osteopontin/genetics/metabolism ; *Pleural Neoplasms/drug therapy ; }, abstract = {BACKGROUND: Malignant Pleural Mesothelioma (MPM) is an aggressive cancer of the mesothelial lining associated with exposure to airborne non-degradable asbestos fibers. Its poor response to currently available treatments prompted us to explore the biological mechanisms involved in its progression. MPM is characterized by chronic non-resolving inflammation; in this study we investigated which inflammatory mediators are mostly expressed in biological tumor samples from MPM patients, with a focus on inflammatory cytokines, chemokines and matrix components.

METHODS: Expression and quantification of Osteopontin (OPN) was detected in tumor and plasma samples of MPM patients by mRNA, immunohistochemistry and ELISA. The functional role of OPN was investigated in mouse MPM cell lines in vivo using an orthotopic syngeneic mouse model.

RESULTS: In patients with MPM, the protein OPN was significantly more expressed in tumors than in normal pleural tissues and predominantly produced by mesothelioma cells; plasma levels were elevated in patients and associated with poor prognosis. However, modulation of OPN levels was not significantly different in a series of 18 MPM patients receiving immunotherapy with durvalumab alone or with pembrolizumab in combination with chemotherapy, some of whom achieved a partial clinical response. Two established murine mesothelioma cell lines: AB1 and AB22 of sarcomatoid and epithelioid histology, respectively, spontaneously produced high levels of OPN. Silencing of the OPN gene (Spp1) dramatically inhibited tumor growth in vivo in an orthotopic model, indicating that OPN has an important promoting role in the proliferation of MPM cells. Treatment of mice with anti-CD44 mAb, blocking a major OPN receptor, significantly reduced tumor growth in vivo.

CONCLUSION: These results demonstrate that OPN is an endogenous growth factor for mesothelial cells and inhibition of its signaling may be helpful to restrain tumor progression in vivo. These findings have translational potential to improve the therapeutic response of human MPM.}, } @article {pmid37361656, year = {2023}, author = {Mishra, K and Siddiquee, S and Mislang, AR}, title = {A rare presentation of malignant mesothelioma of the tunica vaginalis managed with immunotherapy and review of the literature.}, journal = {Clinical case reports}, volume = {11}, number = {6}, pages = {e7610}, pmid = {37361656}, issn = {2050-0904}, abstract = {KEY CLINICAL MESSAGE: We describe the first case in literature of malignant mesothelioma of the tunica vaginalis that has shown partial response to systemic immunotherapy (ipilimumab-nivolumab) post orchiectomy, warranting further investigation in a trial setting.

ABSTRACT: We present a case report of an 80-year-old ex-smoker with a rare diagnosis of metastatic mesothelioma of the tunica vaginalis, managed with immunotherapy. The patient, with no known history of asbestos exposure, presented with a left scrotal mass and pain. Scrotal ultrasound confirmed a large paratesticular mass, and computed tomography (CT) of the chest, abdomen, and pelvis revealed a bilobed mass in the left scrotal compartment without associated inguinal or abdominopelvic lymphadenopathy, and an indeterminate, subcentimeter, bi-basal subpleural nodules. He underwent a left orchiectomy, and histopathology confirmed the diagnosis of a paratesticular mesothelioma. Postoperatively, the patient had a positron emission tomography (PET) scan showing a new right pleural effusion as well as increasing size of the lobar and pleural nodules bilaterally, all metabolically active and suggestive of progressive metastatic disease. The patient was commenced on ipilimumab and nivolumab immunotherapy, a regimen indicated for malignant pleural mesothelioma; however, the efficacy on paratesticular mesothelioma is not known. After 6 months of treatment, the patient demonstrated a partial response to immunotherapy, with a reduction in the size of known pleural nodules and effusion.Literature review suggests that diagnosis requires a high index of suspicion and patients commonly have metastatic disease at the time of diagnosis. Orchiectomy is a common management modality. However, the role, regimen, and benefits of systemic therapy are unclear, warranting further studies investigating management strategies.}, } @article {pmid37359917, year = {2023}, author = {Charlaix Hidalgo, AL and Roux, A and Charissoux, A and Mathonnet, M and Descazeaud, A and Durand Fontanier, S and Taibi, A}, title = {First Case of Abdominal and Tunica Vaginalis Multicystic Benign Mesothelioma: Management and Review of Literature.}, journal = {Indian journal of surgical oncology}, volume = {14}, number = {Suppl 1}, pages = {92-96}, pmid = {37359917}, issn = {0975-7651}, abstract = {Multicystic benign mesothelioma is a rare tumor that affects the serosa. Most cases present with peritoneal lesions exclusively. Some identified risk factors are chronic abdominal inflammation, woman of childbearing age, and asbestos exposure. The symptomatology is not specific and can delay the diagnosis. There are no guidelines for the treatment of this pathology. We describe one male patient with abdominal and tunica vaginalis localizations of multicystic benign mesothelioma. The diagnosis was suspected on imaging and confirmed with histological examination. The treatment on an expert center was complete cytoreduction surgery and HIPEC, but the patient had two recurrences during the 2-year of follow-up. This is the first case of simultaneous rare localizations of multicystic benign mesothelioma. No new risk factors were identified. The case underlines the importance of regular examination of all serosa localizations.}, } @article {pmid37359063, year = {2023}, author = {Singh, R and Frank, AL}, title = {Analysis of the Indian Government's position on the use of asbestos and its health effects.}, journal = {Public health action}, volume = {13}, number = {2}, pages = {50-52}, pmid = {37359063}, issn = {2220-8372}, abstract = {Based on WHO guidance, all forms of asbestos are a health risk. In India, the mining of asbestos has been stopped, but chrysotile (a type of asbestos) is still imported and processed in large quantities. Chrysotile is mainly used for asbestos-cement roofing, and the manufacturers claim its use to be safe. We sought to understand the Indian Government's position on the use of asbestos. To do so, we have analysed the replies of the executive wing of the Indian Government to questions on asbestos in the Indian Parliament. This revealed that, despite a mining ban, the government has defended the import, processing and continued use of asbestos.}, } @article {pmid37347449, year = {2024}, author = {Mejia-Garcia, A and Bonilla, DA and Ramirez, CM and Escobar-Díaz, FA and Combita, AL and Forero, DA and Orozco, C}, title = {Genes and Pathways Involved in the Progression of Malignant Pleural Mesothelioma: A Meta-analysis of Genome-Wide Expression Studies.}, journal = {Biochemical genetics}, volume = {62}, number = {1}, pages = {352-370}, pmid = {37347449}, issn = {1573-4927}, support = {CV2022-CSD-B-12516//Fundación Universitaria del Area Andina/ ; }, mesh = {Humans ; *Mesothelioma, Malignant ; *Mesothelioma/genetics/metabolism ; Phosphatidylinositol 3-Kinases ; *Pleural Neoplasms/genetics/metabolism ; *Lung Neoplasms/pathology ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare and aggressive neoplasm of the pleural tissue that lines the lungs and is mainly associated with long latency from asbestos exposure. This tumor has no effective therapeutic opportunities nowadays and has a very low five-year survival rate. In this sense, identifying molecular events that trigger the development and progression of this tumor is highly important to establish new and potentially effective treatments. We conducted a meta-analysis of genome-wide expression studies publicly available at the Gene Expression Omnibus (GEO) and ArrayExpress databases. The differentially expressed genes (DEGs) were identified, and we performed functional enrichment analysis and protein-protein interaction networks (PPINs) to gain insight into the biological mechanisms underlying these genes. Additionally, we constructed survival prediction models for selected DEGs and predicted the minimum drug inhibition concentration of anticancer drugs for MPM. In total, 115 MPM tumor transcriptomes and 26 pleural tissue controls were analyzed. We identified 1046 upregulated DEGs in the MPM samples. Cellular signaling categories in tumor samples were associated with the TNF, PI3K-Akt, and AMPK pathways. The inflammatory response, regulation of cell migration, and regulation of angiogenesis were overrepresented biological processes. Expression of SOX17 and TACC1 were associated with reduced survival rates. This meta-analysis identified a list of DEGs in MPM tumors, cancer-related signaling pathways, and biological processes that were overrepresented in MPM samples. Some therapeutic targets to treat MPM are suggested, and the prognostic potential of key genes is shown.}, } @article {pmid37309879, year = {2023}, author = {Vimercati, L and Cavone, D and De Maria, L and Caputi, A and Pentimone, F and Sponselli, S and Delvecchio, G and Chellini, E and Binazzi, A and Di Marzio, D and Mensi, C and Consonni, D and Migliore, E and Mirabelli, D and Angelini, A and Martini, A and Negro, C and D'Agostin, F and Grappasonni, I and Pascucci, C and Benfatto, L and Malacarne, D and Casotto, V and Comiati, V and Storchi, C and Mangone, L and Murano, S and Rossin, L and Tallarigo, F and Vitale, F and Verardo, M and Eccher, S and Madeo, G and Staniscia, T and Carrozza, F and Cozzi, I and Romeo, E and Pelullo, P and Labianca, M and Melis, M and Cascone, G and Marinaccio, A and Ferri, GM and Serio, G}, title = {Mesothelioma Risk among Construction Workers According to Job Title: Data from the Italian Mesothelioma Register.}, journal = {La Medicina del lavoro}, volume = {114}, number = {3}, pages = {e2023025}, pmid = {37309879}, issn = {0025-7818}, mesh = {Humans ; *Construction Industry ; *Mesothelioma ; *Mesothelioma, Malignant ; *Occupational Health ; Registries ; }, abstract = {BACKGROUND: An increased risk of mesothelioma has been reported in various countries for construction workers. The Italian National Mesothelioma Registry, from 1993 to 2018, reported exposure exclusively in the construction sector in 2310 cases. We describe the characteristics of these cases according to job title.

METHODS: We converted into 18 groups the original jobs (N=338) as reported by ISTAT codes ('ATECO 91'). The exposure level was attributed at certain, probable and possible in accordance with the qualitative classification of exposure as reported in the Registry guidelines. Descriptive analysis by jobs highlights the total number of subjects for each single job and certain exposure, in descending order, insulator, plumbing, carpenter, mechanic, bricklayer, electrician, machine operator, plasterer, building contractor, painter and labourer.

RESULTS: The cases grow for plumbing in the incidence periods 1993-2018, while, as expected, it decreases for insulator. Within each period considered the most numerous cases are always among bricklayers and labourers, these data confirm the prevalence of non-specialised "interchangeable" jobs in Italian construction sector in the past.

CONCLUSIONS: Despite the 1992 ban, the construction sector still presents an occupational health prevention challenge, circumstances of exposure to asbestos may still occur due to incomplete compliance with prevention and protection measures.}, } @article {pmid37306905, year = {2023}, author = {Tamanna, MT and Egbune, C}, title = {Traditional Treatment Approaches and Role of Immunotherapy in Lung Malignancy and Mesothelioma.}, journal = {Cancer treatment and research}, volume = {185}, number = {}, pages = {79-89}, pmid = {37306905}, issn = {0927-3042}, mesh = {Humans ; B7-H1 Antigen ; *Carcinoma, Non-Small-Cell Lung ; Immunotherapy ; *Lung Neoplasms ; *Mesothelioma ; *Mesothelioma, Malignant ; Nivolumab ; Programmed Cell Death 1 Receptor ; Receptors, Death Domain ; }, abstract = {There is no denying that many revolutions took place in the fight against cancer during the last decades. However, cancers have always managed to find new ways to challenge humankinds. Variable genomic epidemiology, socio-economic differences and limitations of widespread screening are the major concerns in cancer diagnosis and early treatment. A multidisciplinary approach is essentially to manage a cancer patient efficiently. Thoracic malignancies including lung cancers and pleural mesothelioma are accountable for little more than 11.6% of the global cancer burden [4]. Mesothelioma is one of the rare cancers, but concern is the incidences are increasing globally. However, the good news is first-line chemotherapy with the combination of immune checkpoints inhibitors (ICIs) in non-small cell lung cancer (NSCLC) and mesothelioma has showed promising respond and improved overall survival (OS) in pivotal clinical trials [10]. ICIs are commonly referred as immunotherapy are antigens on the cancer cells, and inhibitors are the antibodies produce by the T cell defence system. By inhibiting immune checkpoints, the cancer cells become visible to be identified as abnormal cells and attack by the body's defence system [17]. The programmed death receptor-1 (PD-1) and programmed death receptor ligand-1 (PD-L1) inhibitors are commonly used immune checkpoint blockers for anti-cancer treatment. PD-1/PD-L1 are proteins produced by immune cells and mimic by cancer cells that are implicated in inhibiting T cell response to regulate our immune system, which results tumour cells escaping the defence mechanism to achieve immune surveillance. Therefore, inhibiting immune checkpoints as well as monoclonal antibodies can lead to effective apoptosis of tumour cells [17]. Mesothelioma is an industrial disease caused by significant asbestos exposure. It is the cancer of the mesothelial tissue which presents in the lining of the mediastinum of pleura, pericardium and peritoneum, most commonly affected sites are pleura of the lung or chest wall lining [9] as route of asbestos exposure is inhalation. Calretinin is a calcium binding protein, typically over exposed in malignant mesotheliomas and the most useful marker even while initial changes take place [5]. On the other hand, Wilm's tumour 1 (WT-1) gene expression on the tumour cells can be related to prognosis as it can elicit immune response, thereby inhibit cell apoptosis. A systematic review and meta-analysis study conducted by Qi et al. has suggested that expression of WT-1 in a solid tumour is fatal however, it gives the tumour cell a feature of immune sensitivity which then acts positively towards the treatment with immunotherapy. Clinical significance of WT-1 oncogene in treatment is still hugely debatable and needs further attention [21]. Recently, Japan has reinstated Nivolumab in patients with chemo-refractory mesothelioma. According to NCCN guidelines, the salvage therapies include Pembrolizumab in PD-L1 positive patients and Nivolumab alone or with Ipilimumab in cancers irrespective of PD-L1 expression [9]. The checkpoint blockers have taken over the biomarker-based research and demonstrated impressive treatment options in immune sensitive and asbestos-related cancers. It can be expected that in near future the immune checkpoint inhibitors will be considered as approved first-line cancer treatment universally.}, } @article {pmid37305461, year = {2023}, author = {Peña-Castro, M and Montero-Acosta, M and Saba, M}, title = {A critical review of asbestos concentrations in water and air, according to exposure sources.}, journal = {Heliyon}, volume = {9}, number = {5}, pages = {e15730}, pmid = {37305461}, issn = {2405-8440}, abstract = {Asbestos, a group of minerals with unique physical and chemical properties, has been widely used in various industries. However, extensive exposure to asbestos fibers, present in the environment, has been linked to several types of cancer, mesothelioma, and asbestosis. Despite worldwide regulations prohibiting or regulating the use of this material, the uncertainty surrounding the concentrations of asbestos fibers in the environment (air and water) from different sources of exposure persists. The objective of this review paper is to identify the levels of asbestos in air and water reported in the literature based on the source of exposure in diverse contexts to assess conformity with the reference limits for this mineral. Initially, the review delineates various forms of exposure and the origin of fiber generation in the environment, whether direct or indirect. Regarding the presence of asbestos in the environment, high concentrations were identified in natural water bodies known as Naturally Occurring Asbestos (NOA), and there is a risk in the process of distributing drinking water due to the presence of asbestos-cement pipes. In the air, studies to determine asbestos concentrations vary based on the sources of exposure in each region or city studied. The presence of asbestos mines around the city and the intensity of vehicular traffic are some of the most relevant sources found to be related to high concentrations of asbestos fibers in the air. The present review paper features a critical review section in each chapter to highlight critical points found in the literature and suggest new methodologies/ideas to standardize future research. It emphasizes the necessity to standardize methods for measuring asbestos concentrations in air and water arising from diverse sources of exposure to enable comparisons between different regions and countries.}, } @article {pmid37302119, year = {2023}, author = {Torén, K and Neitzel, RL and Eriksson, HP and Andersson, E}, title = {Cancer incidence among workers in soft paper mills: A cohort study.}, journal = {American journal of industrial medicine}, volume = {66}, number = {9}, pages = {728-735}, doi = {10.1002/ajim.23508}, pmid = {37302119}, issn = {1097-0274}, mesh = {Male ; Humans ; Female ; Cohort Studies ; Incidence ; *Occupational Diseases/epidemiology/etiology ; *Neoplasms/chemically induced/epidemiology ; *Mesothelioma/epidemiology ; *Mesothelioma, Malignant ; *Pleural Neoplasms ; *Occupational Exposure/adverse effects ; *Sarcoma/complications ; Dust ; }, abstract = {OBJECTIVES: To elucidate whether occupational exposure to soft paper dust increases the incidence of cancer.

METHODS: We studied 7988 workers in Swedish soft paper mills from 1960 to 2008, of whom 3233 (2 187 men and 1046 women) had more than 10 years of employment. They were divided into high exposure (>5 mg/m[3] for >1 year) or lower exposure to soft paper dust based on a validated job-exposure matrix. They were followed from 1960 to 2019, and person-years at risk were stratified according to gender, age, and calendar-year. The expected numbers of incident tumors were calculated using the Swedish population as the reference, and standardized incidence ratios (SIR) with 95% confidence intervals (95% CI) were assessed.

RESULTS: Among high-exposure workers with more than 10 years of employment, there was an increased incidence of colon cancer (SIR 1.66, 95% CI 1.20-2.31), small intestine cancer (SIR 3.27, 95% CI 1.36-7.86), and thyroid gland cancer (SIR 2.68, 95% CI 1.11-6.43), as well as lung cancer (SIR 1.56, 95% CI 1.12-2.19). Among the lower-exposed workers there was an increased incidence of connective tissue tumors (sarcomas) (SIR 2.26, 95% CI 1.13-4.51) and pleural mesothelioma (SIR 3.29, 95% CI 1.37-7.91).

CONCLUSION: Workers in soft paper mills with high exposure to soft paper dust have an increased incidence of large and small intestine tumors. Whether the increased risk is caused by paper dust exposure or some unknown associated factors is unclear. The increased incidence of pleural mesothelioma is probably linked to asbestos exposure. The reason for increased incidence of sarcomas is unknown.}, } @article {pmid37297561, year = {2023}, author = {Fazzo, L and Minelli, G and De Santis, M and Ceccarelli, E and Iavarone, I and Zona, A}, title = {The Epidemiological Surveillance of Mesothelioma Mortality in Italy as a Tool for the Prevention of Asbestos Exposure.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {11}, pages = {}, pmid = {37297561}, issn = {1660-4601}, mesh = {Male ; Female ; Humans ; *Mesothelioma, Malignant ; *Mesothelioma/epidemiology ; *Asbestos ; Italy/epidemiology ; Asbestos, Amphibole ; *Occupational Exposure ; }, abstract = {As part of a surveillance plan active since the early 1990s, this study evaluates malignant mesothelioma (MM) mortality for the time-window 2010-2019 in Italy, a country that banned asbestos in 1992. National and regional mortality rates for MM, and municipal standardized mortality ratios (all mesotheliomas, pleural (MPM) and peritoneal (MPeM)), by gender and age group were calculated. A municipal clustering analysis was also performed. There were 15,446 deaths from MM (11,161 males, 3.8 × 100,000; 4285 females, 1.1 × 100,000), of which 12,496 were MPM and 661 were MPeM. In the study period, 266 people ≤50 years died from MM. A slightly decreasing rate among males since 2014 was observed. The areas at major risk hosted asbestos-cement plants, asbestos mines (chrysotile in Balangero), shipyards, petrochemical and chemical plants, and refineries. Female mortality excesses particularly were found in municipalities with a fluoro-edenite-contaminated mine (Biancavilla) and textile facilities. Excesses were also found in a region with the presence of natural asbestos fibres and in males living in two small islands. The Italian National Prevention Plan stated recommendations to eliminate asbestos exposures and to implement health surveillance and healthcare for people exposed to asbestos.}, } @article {pmid37296902, year = {2023}, author = {Rondon, L and Fu, R and Patel, MR}, title = {Success of Checkpoint Blockade Paves the Way for Novel Immune Therapy in Malignant Pleural Mesothelioma.}, journal = {Cancers}, volume = {15}, number = {11}, pages = {}, pmid = {37296902}, issn = {2072-6694}, abstract = {Malignant pleural mesothelioma (MPM) is a malignancy associated with asbestos exposure and is typically categorized as an orphan disease. Recent developments in immunotherapy with anti-PD-1 and anti-CTLA-4 antibodies, specifically with agents nivolumab and ipilimumab, have demonstrated an improvement in overall survival over the previous standard chemotherapy leading to their FDA-approval as first-line therapy for unresectable disease. For quite some time, it has been known that these proteins are not the only ones that function as immune checkpoints in human biology, and the hypothesis that MPM is an immunogenic disease has led to an expanding number of studies investigating alternative checkpoint inhibitors and novel immunotherapy for this malignancy. Early trials are also supporting the notion that therapies that target biological molecules on T cells, cancer cells, or that trigger the antitumor activity of other immune cells may represent the future of MPM treatment. Moreover, mesothelin-targeted therapies are thriving in the field, with forthcoming results from multiple trials signaling an improvement in overall survival when combined with other immunotherapy agents. The following manuscript will review the current state of immune therapy for MPM, explore the knowledge gaps in the field, and discuss ongoing novel immunotherapeutic research in early clinical trials.}, } @article {pmid37295554, year = {2023}, author = {Schaefer, IM and Mariño-Enríquez, A and Hammer, MM and Padera, RF and Sholl, LM}, title = {Recurrent Tumor Suppressor Alterations in Primary Pericardial Mesothelioma.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {36}, number = {9}, pages = {100237}, pmid = {37295554}, issn = {1530-0285}, support = {K08 CA241085/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Male ; Female ; Aged ; *Lung Neoplasms/pathology ; Neoplasm Recurrence, Local ; *Mesothelioma, Malignant ; *Mesothelioma/diagnosis ; *Pleural Neoplasms/pathology ; *Heart Neoplasms/genetics ; *Thymus Neoplasms ; Ubiquitin Thiolesterase/genetics/metabolism ; Biomarkers, Tumor/genetics/metabolism ; }, abstract = {Primary pericardial mesotheliomas are extremely rare, accounting for <1% of all mesotheliomas, and their molecular genetic features and predisposing factors remain to be determined. Here, we report the clinicopathologic, immunohistochemical, and molecular genetic findings of 3 pericardial mesotheliomas without pleural involvement. Three cases diagnosed between 2004 and 2022 were included in the study and analyzed by immunohistochemistry and targeted next-generation sequencing (NGS); corresponding nonneoplastic tissue was sequenced in all cases. Two patients were female and 1 was male, aged between 66 and 75 years. Two patients each had prior asbestos exposure and were smokers. Histologic subtypes were epithelioid in 2 cases and biphasic in 1 case. Immunohistochemical staining identified expression of cytokeratin AE1/AE3 and calretinin in all cases, D2-40 in 2 cases, and WT1 in 1 case. Staining for tumor suppressors revealed loss of p16, MTAP, and Merlin (NF2) expression in 2 cases and loss of BAP1 and p53 in 1 case. Abnormal cytoplasmic BAP1 expression was observed in an additional case. Protein expression abnormalities correlated with NGS results, which showed concurrent complete genomic inactivation of CDKN2A/p16, CDKN2B, MTAP, and NF2 in 2 mesotheliomas and of BAP1 and TP53 in 1 mesothelioma each, respectively. In addition, 1 patient harbored a pathogenic BRCA1 germline mutation, which resulted in biallelic inactivation in the mesothelioma. All mesotheliomas were mismatch repair proficient and showed several chromosomal gains and losses. All patients died from disease. Our study demonstrates that pericardial mesotheliomas share common morphologic, immunohistochemical, and molecular genetic features with pleural mesothelioma, including recurrent genomic inactivation of canonical tumor suppressors. Our study adds new insights into the genetic landscape of primary pericardial mesothelioma and highlights BRCA1 loss as a potential contributing factor in a subset of cases, thereby contributing to refined precision diagnostics for this rare cancer.}, } @article {pmid37293522, year = {2023}, author = {Tagliaferri, AR and Melki, G and Rezkalla, A and Baddoura, W}, title = {Diffuse malignant peritoneal mesothelioma presenting as small bowel obstruction.}, journal = {Radiology case reports}, volume = {18}, number = {8}, pages = {2681-2684}, pmid = {37293522}, issn = {1930-0433}, abstract = {Mesotheliomas are aggressive malignant tumors which can occur most commonly in the pleural space, however can occur in the peritoneum in those with an extensive history of asbestos exposure. Primary peritoneal mesothelioma is relatively rare and is a fatal diagnosis. The prognosis of primary peritoneal mesothelioma is very poor and individuals are at high risk of developing mesothelioma in another cavity within the first year after initial diagnosis. Herein, we present a case of primary peritoneal mesothelioma, presenting as small bowel obstruction.}, } @article {pmid37292347, year = {2023}, author = {Migliore, M and Fiore, M and Filippini, T and Tumino, R and Sabbioni, M and Spatola, C and Polosa, R and Vigneri, P and Nardini, M and Castorina, S and Basile, F and Ferrante, M and , }, title = {Comparison of video-assisted pleurectomy/decortication surgery plus hyperthermic intrathoracic chemotherapy with VATS talc pleurodesis for the treatment of malignant pleural mesothelioma: A pilot study.}, journal = {Heliyon}, volume = {9}, number = {6}, pages = {e16685}, pmid = {37292347}, issn = {2405-8440}, abstract = {Hyperthermic intrathoracic chemotherapy (HITHOC) adjunct to surgery for Malignant Pleural Mesothelioma (MPM) has no definite role. The primary objective of this pilot-trial was to evaluate the feasibility for future large studies. The study design was a prospective randomized three-centric pilot trial. We recruited patients diagnosed with MPM and prospectively assigned them to two groups: Group A: Video Assisted Thoracic Surgery (VATS) talc pleurodesis or Group B: Video-assisted P/D plus HITHOC. From November-2011 to July-2017 24 males and 3 females, with a median age of 68-years were enrolled (recruitment rate 5 patients/year). Preoperative stage was I-II, and 18 had epithelioid type. 14 patients were in the Group A. Operative mortality was 0. Follow-up ranged 6-80 months. The median overall survival time started to diverge at 20 months, being 19 months (95% CI 12-25) in Group A and 28 months (95% CI 0-56) in Group B. Survival rate for the epithelioid type was 15 months (95% CI 0-34) in Group A and 45 months (95% CI 0-107) in the Group B. These findings suggest that video-assisted P/D plus HITHOC may improve survival time in MPM patients undergoing surgical treatment and support the need for a larger multicenter randomized clinical trial.}, } @article {pmid37254056, year = {2023}, author = {Ito, F and Kato, K and Yanatori, I and Maeda, Y and Murohara, T and Toyokuni, S}, title = {Matrigel-based organoid culture of malignant mesothelioma reproduces cisplatin sensitivity through CTR1.}, journal = {BMC cancer}, volume = {23}, number = {1}, pages = {487}, pmid = {37254056}, issn = {1471-2407}, support = {JP18J13646, JP20K22805 and JP21K15484//Japan Society for the Promotion of Science/ ; JP20K17145, JP22K08123//Japan Society for the Promotion of Science/ ; JP19H05462 and JP20H05502//Japan Society for the Promotion of Science/ ; JPMJCR19H4//Core Research for Evolutional Science and Technology/ ; 19-25126//Princess Takamatsu Cancer Research Fund/ ; }, mesh = {Animals ; Humans ; Mice ; *Cisplatin/pharmacology ; Collagen/metabolism ; *Mesothelioma, Malignant/metabolism ; Organoids/pathology ; *Copper Transporter 1/metabolism ; }, abstract = {Organoids are a three-dimensional (3D) culture system that simulate actual organs. Therefore, tumor organoids are expected to predict precise response to chemotherapy in patients. However, to date, few studies have studied the drug responses in organoids of malignant mesothelioma (MM). The poor prognosis of MM emphasizes the importance of establishing a protocol for generating MM-organoid for research and clinical use. Here, we established murine MM organoids from p53[+/-] or wild-type C57BL/6 strain by intraperitoneal injection either with crocidolite or carbon nanotube. Established MM-organoids proliferated in Matrigel as spheroids. Subcutaneous injection assays revealed that the MM-organoids mimicked actual tissue architecture and maintained the original histological features of the primary MM. RNA sequencing and pathway analyses revealed that the significant expressional differences between the 2D- and 3D-culture systems were observed in receptor tyrosine kinases, including IGF1R and EGFR, glycosylation and cholesterol/steroid metabolism. MM-organoids exhibited a more sensitive response to cisplatin through stable plasma membrane localization of a major cisplatin transporter, copper transporter 1/Slc31A1 (Ctr1) in comparison to 2D-cultures, presumably through glycosylation and lipidation. The Matrigel culture system facilitated the localization of CTR1 on the plasma membrane, which simulated the original MMs and the subcutaneous xenografts. These results suggest that the newly developed protocol for MM-organoids is useful to study strategies to overcome chemotherapy resistance to cisplatin.}, } @article {pmid37253383, year = {2023}, author = {Nash, A and Firth Née Phan, T and Creaney, J}, title = {New Markers for Management of Mesothelioma.}, journal = {Seminars in respiratory and critical care medicine}, volume = {44}, number = {4}, pages = {491-501}, doi = {10.1055/s-0043-1769097}, pmid = {37253383}, issn = {1098-9048}, mesh = {Humans ; *Mesothelioma, Malignant ; *Lung Neoplasms/diagnosis/drug therapy/genetics ; *Mesothelioma/diagnosis/therapy ; *Pleural Neoplasms/diagnosis/drug therapy ; Biomarkers, Tumor/genetics ; }, abstract = {In this review, we provide an update on the status of cancer biomarkers for the clinical management of pleural mesothelioma, an aggressive cancer associated with asbestos exposure. Mesothelioma can be difficult to diagnose, and response to treatment is transient, even with recently adopted immune checkpoint inhibitor (ICI) combinations. Identification of mesothelioma-specific biomarkers could facilitate early diagnosis and tailor treatment strategies. Mesothelioma is characterized by frequent loss or alteration of the tumor suppressor genes cyclin-dependent kinase inhibitor 2A (CDKN2A) and BRCA1-associated protein-1 (BAP1). Accumulating data show these genes and/or their related protein products will be valuable tissue-based biomarkers for mesothelioma. Loss of BAP1, CDKN2A, p16, or methylthioadenosine phosphorylase provide pathologists with a reliable means of differentiating between mesothelioma and reactive mesothelial cell proliferations. This can aid diagnosis in difficult cases and is requisite for the identification of the new pathological entity malignant mesothelioma in situ. However, limited progress in identifying clinically useful soluble biomarkers in this cancer type has been made, with mesothelin remaining the benchmark. To date, results from studies to identify predictive biomarkers for ICI response have been disappointing. A recent retrospective study demonstrated BAP1 loss was predictive of improved survival following combination pemetrexed- and platinum-based chemotherapy. Validation of this result could have important clinical implications. Clinical trials aimed at targeting therapy based on biomarker expression are generally in the early phase setting, with overall results being moderate. The identification of biomarkers for mesothelioma remains a key research question due to their potential to improve patient outcomes in this deadly cancer.}, } @article {pmid37248188, year = {2023}, author = {Zhao, F and Zhang, YL and Liu, X and Chen, TH and Li, J}, title = {[A case of malignant peritoneal mesothelioma].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {41}, number = {4}, pages = {307-309}, doi = {10.3760/cma.j.cn121094-20220328-00158}, pmid = {37248188}, issn = {1001-9391}, mesh = {Humans ; *Mesothelioma, Malignant/drug therapy ; *Mesothelioma/diagnosis ; Pemetrexed/therapeutic use ; Cisplatin/therapeutic use ; *Peritoneal Neoplasms/diagnosis ; *Pleural Neoplasms ; *Lung Neoplasms/drug therapy ; }, abstract = {Malignant mesothelioma is a highly malignant disease that most often occurs in the pleural cavity, followed by the peritoneum and pericardium. Malignant peritoneal mesothelioma (MPM) accounts for 10%-15% of all mesothelioma. The most important risk factor for MPM is exposure to asbestos. MPM has no specific clinical symptoms, imaging and histopathology are critical for the diagnosis. There are currently no generally accepted guidelines for curative treatment of MPM. The patient mainly presented with abdominal pain, abdominal distension and discomfort. Due to extensive omentum metastasis, no further surgical treatment was performed. Pemetrexed combined with cisplatin chemotherapy was given for 2 cycles, and the patient is still alive.}, } @article {pmid37247334, year = {2023}, author = {Ntlailane, L and Sebola, L and Singo, D and Nthoke, T and Mizan, G}, title = {Managing the risks of an asbestos bulk storage facility at a research institute.}, journal = {Annals of work exposures and health}, volume = {67}, number = {7}, pages = {907-911}, doi = {10.1093/annweh/wxad028}, pmid = {37247334}, issn = {2398-7316}, mesh = {Humans ; *Mesothelioma ; *Occupational Exposure ; *Asbestos ; Asbestos, Crocidolite ; Academies and Institutes ; }, abstract = {The South African National Institute for Occupational Health (NIOH), formerly the Pneumoconiosis Research Unit, has previously milled about 544 kg of anthophyllite, crocidolite, amosite and chrysotile asbestos fibre materials. This endeavour came about in an attempt to address a recommendation, made by the International Union Against Cancer (UICC), to make asbestos standard reference samples available for research. Some of these reference samples, as well as the bulk, unprocessed materials are still within the care of the NIOH and can be obtained for the purpose of Public Health research under strict terms and conditions. Considering the hazardous nature of asbestos and regulated prohibitions imposed on this mineral, the NIOH asbestos storage facility is being subjected to various occupational and environmental control measures to ensure that any potential fibre release, and subsequent risk of exposure, are prevented.}, } @article {pmid37232345, year = {2023}, author = {Broggi, G and Filetti, V and Magro, G and Morante, B and Garro, R and Ledda, C and Rapisarda, V and Lombardo, C and Loreto, C and Caltabiano, R}, title = {Immunohistochemical expression of cAMP in fluoroedenite‑induced malignant pleural mesothelioma: Preliminary results.}, journal = {Molecular medicine reports}, volume = {28}, number = {1}, pages = {}, doi = {10.3892/mmr.2023.13019}, pmid = {37232345}, issn = {1791-3004}, mesh = {Male ; Female ; Humans ; Middle Aged ; Aged ; Aged, 80 and over ; *Mesothelioma, Malignant ; *Mesothelioma/chemically induced/metabolism ; *Lung Neoplasms/pathology ; *Asbestos ; }, abstract = {Despite advances in understanding of the biology of malignant pleural mesothelioma (MPM), the prognosis of this malignancy remains poor. Although asbestos still remains the main pathogenic agent of MPM, other asbestos‑like fibers such as fluoro‑edenite (FE) fibers, induce MPM. Notable incidence and mortality rates of MPM have been found in Biancavilla, Italy, where FE fibers have been extracted from building materials for >50 years. Cyclic adenosine monophosphate (cAMP) is a secondary messenger that plays a key role in several physiological and pathological mechanisms regulating protein kinase A (PKA) and the CREB pathway. Hyperactivation of the cAMP/PKA/CREB pathway is involved in many neoplastic processes, including tumor cell proliferation, invasion and metastatic spread. The present study investigated immunohistochemical expression of cAMP in patients with FE‑induced MPM, which included six males and four females with an age range of 50‑93 years. There was high immunoexpression of cAMP in 5 out of 10 tumors while the remaining 5 cases showed low immunoexpression. In addition, there was a correlation between cAMP overexpression and decreased survival times (mean overall survival times, 7.5 months in high expression group vs. 18 months in low expression group).}, } @article {pmid37220527, year = {2023}, author = {Wang, D and Zhu, J and Li, N and Lu, H and Gao, Y and Zhuang, L and Chen, Z and Mao, W}, title = {GC-MS-based untargeted metabolic profiling of malignant mesothelioma plasma.}, journal = {PeerJ}, volume = {11}, number = {}, pages = {e15302}, pmid = {37220527}, issn = {2167-8359}, mesh = {Humans ; *Mesothelioma, Malignant ; Gas Chromatography-Mass Spectrometry ; Metabolomics ; Alanine ; }, abstract = {BACKGROUND: Malignant mesothelioma (MM) is a cancer caused mainly by asbestos exposure, and is aggressive and incurable. This study aimed to identify differential metabolites and metabolic pathways involved in the pathogenesis and diagnosis of malignant mesothelioma.

METHODS: By using gas chromatography-mass spectrometry (GC-MS), this study examined the plasma metabolic profile of human malignant mesothelioma. We performed univariate and multivariate analyses and pathway analyses to identify differential metabolites, enriched metabolism pathways, and potential metabolic targets. The area under the receiver-operating curve (AUC) criterion was used to identify possible plasma biomarkers.

RESULTS: Using samples from MM (n = 19) and healthy control (n = 22) participants, 20 metabolites were annotated. Seven metabolic pathways were disrupted, involving alanine, aspartate, and glutamate metabolism; glyoxylate and dicarboxylate metabolism; arginine and proline metabolism; butanoate and histidine metabolism; beta-alanine metabolism; and pentose phosphate metabolic pathway. The AUC was used to identify potential plasma biomarkers. Using a threshold of AUC = 0.9, five metabolites were identified, including xanthurenic acid, (s)-3,4-hydroxybutyric acid, D-arabinose, gluconic acid, and beta-d-glucopyranuronic acid.

CONCLUSIONS: To the best of our knowledge, this is the first report of a plasma metabolomics analysis using GC-MS analyses of Asian MM patients. Our identification of these metabolic abnormalities is critical for identifying plasma biomarkers in patients with MM. However, additional research using a larger population is needed to validate our findings.}, } @article {pmid37220304, year = {2023}, author = {Korchevskiy, AA and Wylie, AG}, title = {Toxicological and epidemiological approaches to carcinogenic potency modeling for mixed mineral fiber exposure: the case of fibrous balangeroite and chrysotile.}, journal = {Inhalation toxicology}, volume = {35}, number = {7-8}, pages = {185-200}, doi = {10.1080/08958378.2023.2213720}, pmid = {37220304}, issn = {1091-7691}, mesh = {Humans ; Asbestos, Serpentine/toxicity ; Mineral Fibers/toxicity ; Carcinogens/toxicity ; Asbestos, Amphibole/toxicity ; *Mesothelioma/chemically induced/epidemiology ; *Mesothelioma, Malignant ; *Lung Neoplasms/chemically induced/epidemiology ; *Asbestos/analysis ; }, abstract = {CONTEXT: Excess mesothelioma risk was observed among chrysotile miners and millers in Balangero, Italy. The mineral balangeroite has been identified in an asbestiform habit from the Balangero chrysotile mine (Italy). Previous studies did not contain a detailed description of the fiber dimensions, thus limiting possible approaches to estimating their carcinogenic potential.

OBJECTIVES: To reconstruct excess mesothelioma risk based on characteristics of mixed fiber exposure.

METHODS: The lengths and widths of particles from a sample of balangeroite were measured by transmission electron microscopy (TEM). Statistical analysis and modeling were applied to assess the toxicological potential of balangeroite.

RESULTS: Balangeroite fibers are characterized as asbestiform, with geometric mean length of 10 μm, width of 0.54 μm, aspect ratio of 19, and specific surface area of 13.8 (1/μm). Proximity analysis shows dimensional characteristics of balangeroite close to asbestiform anthophyllite. Modeling estimates the average potency of balangeroite as 0.04% (95% CI 0.0058, 0.16) based on dimensional characteristics and 0.05% (95% CI-0.04, 0.24) based on epidemiological data. The available estimate of the fraction of balangeroite in the Balangero mine is very approximate. There were no data for airborne balangeroite fibers from the Balangero mine and no lung burden data are available. All estimates were performed using weight fractions of balangeroite and chrysotile. However, based on reasonable assumptions, of the seven cases of mesothelioma in the cohort, about three cases (43%) can be attributed to fibrous balangeroite.

CONCLUSION: The presence of different types of mineral fibers in aerosolized materials even in small proportions can explain observed cancer risks.}, } @article {pmid37217834, year = {2023}, author = {Zambrano, E and Matoso, A and Reyes-Múgica, M}, title = {Mesotheliomas in Children.}, journal = {Advances in anatomic pathology}, volume = {30}, number = {4}, pages = {275-279}, doi = {10.1097/PAP.0000000000000403}, pmid = {37217834}, issn = {1533-4031}, mesh = {Adult ; Humans ; Child ; *Mesothelioma/genetics/pathology ; *Asbestos ; }, abstract = {Mesotheliomas are rare and aggressive tumors that originate from mesothelial cells. Although exceedingly rare, these tumors may occur in children. Different from adult mesotheliomas, however, environmental exposures particularly to asbestos do not appear to play a major role in mesotheliomas in children, in whom specific genetic rearrangements driving these tumors have been identified in recent years. These molecular alterations may increasingly offer opportunities for targeted therapies in the future, which may provide better outcomes for these highly aggressive malignant neoplasms.}, } @article {pmid37210180, year = {2023}, author = {Carbone, M and Yang, H and Pass, HI and Taioli, E}, title = {Did the Ban on Asbestos Reduce the Incidence of Mesothelioma?.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {18}, number = {6}, pages = {694-697}, doi = {10.1016/j.jtho.2023.03.013}, pmid = {37210180}, issn = {1556-1380}, support = {R01 ES030948/ES/NIEHS NIH HHS/United States ; R01 CA237235/CA/NCI NIH HHS/United States ; R01 CA198138/CA/NCI NIH HHS/United States ; U01 CA214195/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Incidence ; *Lung Neoplasms/epidemiology/prevention & control/complications ; *Mesothelioma/epidemiology/prevention & control/etiology ; *Mesothelioma, Malignant ; *Asbestos/adverse effects ; *Occupational Exposure/adverse effects/prevention & control ; }, } @article {pmid37199503, year = {2023}, author = {Giacobbe, C and Moliterni, A and Di Giuseppe, D and Malferrari, D and Wright, JP and Mattioli, M and Raneri, S and Giannini, C and Fornasini, L and Mugnaioli, E and Ballirano, P and Gualtieri, AF}, title = {The crystal structure of the killer fibre erionite from Tuzköy (Cappadocia, Turkey).}, journal = {IUCrJ}, volume = {10}, number = {Pt 4}, pages = {397-410}, pmid = {37199503}, issn = {2052-2525}, support = {20173X8WA4//PRIN: Progetti di Ricerca di Rilevante Interesse Nazionale-Bando 2017-Prot/ ; }, abstract = {Erionite is a non-asbestos fibrous zeolite classified by the International Agency for Research on Cancer (IARC) as a Group 1 carcinogen and is considered today similar to or even more carcinogenic than the six regulated asbestos minerals. Exposure to fibrous erionite has been unequivocally linked to cases of malignant mesothelioma (MM) and this killer fibre is assumed to be directly responsible for more than 50% of all deaths in the population of the villages of Karain and Tuzköy in central Anatolia (Turkey). Erionite usually occurs in bundles of thin fibres and very rarely as single acicular or needle-like fibres. For this reason, a crystal structure of this fibre has not been attempted to date although an accurate characterization of its crystal structure is of paramount importance for our understanding of the toxicity and carcinogenicity. In this work, we report on a combined approach of microscopic (SEM, TEM, electron diffraction), spectroscopic (micro-Raman) and chemical techniques with synchrotron nano-single-crystal diffraction that allowed us to obtain the first reliable ab initio crystal structure of this killer zeolite. The refined structure showed regular T-O distances (in the range 1.61-1.65 Å) and extra-framework content in line with the chemical formula (K2.63Ca1.57Mg0.76Na0.13Ba0.01)[Si28.62Al7.35]O72·28.3H2O. The synchrotron nano-diffraction data combined with three-dimensional electron diffraction (3DED) allowed us to unequivocally rule out the presence of offretite. These results are of paramount importance for understanding the mechanisms by which erionite induces toxic damage and for confirming the physical similarities with asbestos fibres.}, } @article {pmid37194050, year = {2023}, author = {RanYue, W and ChunYan, W and Likun, H and LiPing, Z and JieLu, L and ZhengWei, D}, title = {Diffuse intrapulmonary mesothelioma mimicking pulmonary lepidic adenocarcinoma: a rare case report and review of the literature.}, journal = {Diagnostic pathology}, volume = {18}, number = {1}, pages = {64}, pmid = {37194050}, issn = {1746-1596}, mesh = {Humans ; In Situ Hybridization, Fluorescence ; *Mesothelioma/diagnosis/pathology ; *Mesothelioma, Malignant/diagnosis ; *Lung Neoplasms/diagnosis/pathology ; *Pleural Neoplasms/pathology ; *Adenocarcinoma of Lung/diagnosis ; *Lung Diseases, Interstitial/diagnosis ; Biomarkers, Tumor/metabolism ; Diagnosis, Differential ; }, abstract = {Mesothelioma, with various clinical manifestations, radiological features, and histomorphological types, can be divided into epithelioid, sarcomatoid, and biphasic types, according to their histomorphological characteristics. There is a rare growth pattern of pleural mesothelioma: diffuse intrapulmonary mesothelioma (DIM), with a distinctive pattern of predominantly intrapulmonary growth, has no or minimal pleural involvement, and simulates interstitial lung disease(ILD) clinically and radiologically. A 59-year-old man presented to the hospital with recurrent pleural effusions for 4 years and a history of asbestos exposure. Computed tomography (CT) showed bilateral pure ground-glass opacity lesions, and the tumor cells showed a lepidic growth pattern pathologically. Immunohistochemical staining was positive for CK, WT-1, calretinin, D2-40, CK5/6, and Claudin4, while TTF-1, CEA, EMA, CK7, CK20, and other epithelial markers were negative. BAP1 loss its expression, and MTAP was positive in cytoplasm. CDKN2A was negative tested by Fluorescence in situ hybridization (FISH). The final diagnosis was DIM. In conclusion, we should recognize this rare disease to avoid misdiagnosis and delayed treatment.}, } @article {pmid37190292, year = {2023}, author = {Ahmadzada, T and Vijayan, A and Vafaee, F and Azimi, A and Reid, G and Clarke, S and Kao, S and Grau, GE and Hosseini-Beheshti, E}, title = {Small and Large Extracellular Vesicles Derived from Pleural Mesothelioma Cell Lines Offer Biomarker Potential.}, journal = {Cancers}, volume = {15}, number = {8}, pages = {}, pmid = {37190292}, issn = {2072-6694}, support = {Corporate/private financial support//Turner Freeman Lawyers/ ; TBC//Dust Diseases Board/ ; }, abstract = {Pleural mesothelioma, previously known as malignant pleural mesothelioma, is an aggressive and fatal cancer of the pleura, with one of the poorest survival rates. Pleural mesothelioma is in urgent clinical need for biomarkers to aid early diagnosis, improve prognostication, and stratify patients for treatment. Extracellular vesicles (EVs) have great potential as biomarkers; however, there are limited studies to date on their role in pleural mesothelioma. We conducted a comprehensive proteomic analysis on different EV populations derived from five pleural mesothelioma cell lines and an immortalized control cell line. We characterized three subtypes of EVs (10 K, 18 K, and 100 K), and identified a total of 4054 unique proteins. Major differences were found in the cargo between the three EV subtypes. We show that 10 K EVs were enriched in mitochondrial components and metabolic processes, while 18 K and 100 K EVs were enriched in endoplasmic reticulum stress. We found 46 new cancer-associated proteins for pleural mesothelioma, and the presence of mesothelin and PD-L1/PD-L2 enriched in 100 K and 10 K EV, respectively. We demonstrate that different EV populations derived from pleural mesothelioma cells have unique cancer-specific proteomes and carry oncogenic cargo, which could offer a novel means to extract biomarkers of interest for pleural mesothelioma from liquid biopsies.}, } @article {pmid37190163, year = {2023}, author = {Collatuzzo, G and Turati, F and Malvezzi, M and Negri, E and La Vecchia, C and Boffetta, P}, title = {Attributable Fraction of Cancer Related to Occupational Exposure in Italy.}, journal = {Cancers}, volume = {15}, number = {8}, pages = {}, pmid = {37190163}, issn = {2072-6694}, support = {22987//Italian Association for Cancer Research/ ; }, abstract = {BACKGROUND: Exposure to occupational carcinogens is an important and avoidable cause of cancer. We aimed to provide an evidence-based estimate of the burden of occupation-related cancers in Italy.

METHODS: The attributable fraction (AF) was calculated based on the counterfactual scenario of no occupational exposure to carcinogens. We included exposures classified as IARC group 1 and with reliable evidence of exposure in Italy. Relative risk estimates for selected cancers and prevalences of exposure were derived from large-scale studies. Except for mesothelioma, a 15-20-year latency period between exposure and cancer was considered. The data on cancer incidence in 2020 and mortality in 2017 in Italy were obtained from the Italian Association of Cancer Registries.

RESULTS: The most prevalent exposures were UV radiation (5.8%), diesel exhaust (4.3%), wood dust (2.3%) and silica dust (2.1%). Mesothelioma had the largest AF to occupational carcinogens (86.6%), followed by sinonasal cancer (11.8%) and lung cancer (3.8%). We estimated that 0.9% of cancer cases (N~3500) and 1.6% of cancer deaths (N~2800) were attributable to occupational carcinogens in Italy. Of these, about 60% were attributable to asbestos, 17.5% to diesel exhaust, followed by chromium and silica dust (7% and 5%).

CONCLUSIONS: Our estimates provide up-to-date quantification of the low, but persistent, burden of occupational cancers in Italy.}, } @article {pmid37189132, year = {2023}, author = {Kauschke, V and Philipp-Gehlhaar, M and Schneider, J}, title = {Expression of microRNAs in leukocytes and serum of asbestosis patients.}, journal = {European journal of medical research}, volume = {28}, number = {1}, pages = {175}, pmid = {37189132}, issn = {2047-783X}, mesh = {Humans ; *MicroRNAs ; *Asbestosis/genetics ; Biomarkers ; *Asbestos ; Leukocytes/metabolism ; }, abstract = {BACKGROUND: Although asbestos use is banned in many countries, long latency of asbestos-related diseases like pleural plaques or asbestosis mean it is still a public health issue. People suffering from these diseases have a higher risk of developing mesothelioma or lung cancer, which can progress quickly and aggressively. MicroRNAs were suggested as potential biomarkers in several diseases. However, in asbestosis, blood microRNAs are less explored. Since miR-32-5p, miR-143-3p, miR-145-5p, miR-146b-5p, miR-204-5p and miR-451a are involved in fibrotic processes and in cancer, expression of these microRNAs was analyzed in leukocytes and serum of asbestosis patients.

METHODS: MicroRNA expression was analyzed in leukocytes and serum of 36 patients (26 affected by pleural plaques and 10 by asbestosis) and 15 healthy controls by real-time RT-PCR. Additionally, data analyses were performed regarding disease severity based on ILO classification.

RESULTS: MicroRNA miR-146b-5p was significantly down-regulated in leukocytes of patients suffering from pleural plaques with a large effect indicated by η[2]p = 0.150 and Cohen's f = 0.42, a value of difference of 0.725 and a 95% confidence interval of 0.070-1.381. In patients suffering from asbestosis miR-146b-5p was not significantly regulated. However, data analyses considering disease severity only, revealed that miR-146b-5p was significantly down-regulated in leukocytes of mildly diseased patients compared to controls with a large effect indicated by η[2]p = 0.178 and Cohen's f = 0.465, a value of difference of 0.848 and a 95% confidence interval of 0.097-1.599. Receiver operating characteristic (ROC) curve and an area under the ROC curve value of 0.757 for miR-146b-5p indicated acceptable discrimination ability between patients suffering from pleural plaques and healthy controls. Less microRNAs were detectable in serum than in leukocytes, showing no significant expression differences in all participants of this study. Moreover, miR-145-5p was regulated significantly differently in leukocytes and serum. An R[2] value of 0.004 for miR-145-5p indicated no correlation in microRNA expression between leukocytes and serum.

CONCLUSION: Leukocytes seem more suitable than serum for microRNA analyses regarding disease and potentially cancer risk assessment of patients suffering from asbestos-related pleural plaques or asbestosis. Long-term studies may reveal whether down-regulation of miR-146b-5p in leukocytes might be an early indicator for an increased cancer risk.}, } @article {pmid37180489, year = {2023}, author = {Sekido, Y and Sato, T}, title = {NF2 alteration in mesothelioma.}, journal = {Frontiers in toxicology}, volume = {5}, number = {}, pages = {1161995}, pmid = {37180489}, issn = {2673-3080}, abstract = {The NF2 tumor suppressor gene is a frequent somatically mutated gene in mesothelioma, with 30%-40% mesotheliomas showing NF2 inactivation. NF2 encodes merlin, a member of the ezrin, radixin, and moesin (ERM) family of proteins that regulate cytoskeleton and cell signaling. Recent genome analysis revealed that NF2 alteration may be a late event in mesothelioma development, suggesting that NF2 mutation confers a more aggressive phenotype to mesothelioma cells and may not be directly caused by asbestos exposure. The Hippo tumor-suppressive and mTOR prooncogenic signaling pathways are crucial cell-signaling cascades regulated by merlin. Although the exact role and timing of NF2 inactivation in mesothelioma cells remain to be elucidated, targeting the NF2/merlin-Hippo pathway may be a new therapeutic strategy for patients with mesothelioma.}, } @article {pmid37178944, year = {2023}, author = {Brown, JS}, title = {Comparison of Oncogenes, Tumor Suppressors, and MicroRNAs Between Schizophrenia and Glioma: The Balance of Power.}, journal = {Neuroscience and biobehavioral reviews}, volume = {151}, number = {}, pages = {105206}, doi = {10.1016/j.neubiorev.2023.105206}, pmid = {37178944}, issn = {1873-7528}, mesh = {Humans ; *MicroRNAs/genetics/metabolism ; *Schizophrenia/genetics ; Oncogenes ; *Glioma/genetics ; }, abstract = {The risk of cancer in schizophrenia has been controversial. Confounders of the issue are cigarette smoking in schizophrenia, and antiproliferative effects of antipsychotic medications. The author has previously suggested comparison of a specific cancer like glioma to schizophrenia might help determine a more accurate relationship between cancer and schizophrenia. To accomplish this goal, the author performed three comparisons of data; the first a comparison of conventional tumor suppressors and oncogenes between schizophrenia and cancer including glioma. This comparison determined schizophrenia has both tumor-suppressive and tumor-promoting characteristics. A second, larger comparison between brain-expressed microRNAs in schizophrenia with their expression in glioma was then performed. This identified a core carcinogenic group of miRNAs in schizophrenia offset by a larger group of tumor-suppressive miRNAs. This proposed "balance of power" between oncogenes and tumor suppressors could cause neuroinflammation. This was assessed by a third comparison between schizophrenia, glioma and inflammation in asbestos-related lung cancer and mesothelioma (ALRCM). This revealed that schizophrenia shares more oncogenic similarity to ALRCM than glioma.}, } @article {pmid37175892, year = {2023}, author = {Cugliari, G}, title = {FKBP5, a Modulator of Stress Responses Involved in Malignant Mesothelioma: The Link between Stress and Cancer.}, journal = {International journal of molecular sciences}, volume = {24}, number = {9}, pages = {}, pmid = {37175892}, issn = {1422-0067}, mesh = {Humans ; *Mesothelioma, Malignant ; *Mesothelioma/pathology ; *Pleural Neoplasms/pathology ; *Asbestos/toxicity ; *Lung Neoplasms/pathology ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare tumour characterized by a long latency period after asbestos exposure and poor survival [...].}, } @article {pmid37172528, year = {2023}, author = {Du, X and Li, X and Zhang, B and Hao, Z and Gao, Y and Jiang, X and Yang, Z and Chen, Y}, title = {The clinicopathological significance of TOP2A expression in malignant peritoneal mesothelioma.}, journal = {Annals of diagnostic pathology}, volume = {65}, number = {}, pages = {152155}, doi = {10.1016/j.anndiagpath.2023.152155}, pmid = {37172528}, issn = {1532-8198}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; *Asbestos ; Ki-67 Antigen/metabolism ; *Lung Neoplasms/pathology ; *Mesothelioma/diagnosis ; *Mesothelioma, Malignant ; *Peritoneal Neoplasms ; *Pleural Neoplasms/metabolism/pathology ; Prognosis ; }, abstract = {BACKGROUND: Malignant peritoneal mesothelioma (MPM) is a rare malignant tumor with a high mortality rate and extremely poor prognosis. TOP2A expression is associated with cell proliferation and cell cycle progression. We aimed to demonstrate the expression profile of TOP2A in MPM and its correlation with clinicopathological features.

METHODS: Clinicopathological information from 100 MPM cases was collected at Beijing Shijitan Hospital, Capital Medical University. Immunohistochemistry (IHC) was performed to evaluate TOP2A levels. The associations between TOP2A levels and clinicopathological features or prognosis were analyzed. Clinical follow-up data were reviewed to determine correlations among the pathological prognostic factors using the Kaplan-Meier estimator and univariate/multivariate Cox proportional hazards regression models.

RESULTS: Among the 100 MPM patients, there were 48 males and 52 females, with a median age of 54 years (range: 24-72 years). The cutoff curve was used to find the boundary value of the TOP2A-positive rate. TOP2A positive rate ≥ 11.97 % accounted for 48 % in tumor tissue. The TOP2A-positive rate was not associated with sex, age, asbestos exposure, peritoneal carcinomatosis index (PCI) score, or completeness of cytoreduction (CC) score in MPM. Univariate analysis revealed survival-related pathological parameters, including asbestos exposure, CA125, histological type, PCI score, CC score, Ki-67 index, and TOP2A positive rate. Multivariate analysis identified that asbestos exposure history, PCI score, Ki-67 proliferation index and TOP2A positive rate in tissue are independent prognostic factors.

CONCLUSIONS: High expression of TOP2A is linked to better prognosis of MPM.}, } @article {pmid37168168, year = {2023}, author = {Singh, R and Frank, AL}, title = {Does the Presence of Asbestos-Containing Materials in Buildings Post-construction and Before Demolition Have an Impact on the Exposure to Occupants in Non-occupational Settings?.}, journal = {Cureus}, volume = {15}, number = {4}, pages = {e37305}, pmid = {37168168}, issn = {2168-8184}, abstract = {This narrative review aims to determine if asbestos-containing materials in buildings pose a hazard to building occupants in non-occupational settings. This paper is limited to the post-construction and pre-demolition stages of a building. The researchers selected 19 studies from the 126 studies screened, concerning exposure to asbestos fibers in non-occupational building settings, with a focus on post-construction and pre-demolition phases. The literature review found that certain conditions, such as the measurement techniques, standards, and previous data availability, prevent a conclusive answer to the research question. Some studies have pointed towards an effect of asbestos-containing materials on health of occupants in non-occupational settings. But, there are some that do not suggest a positive relationship between non-occupational exposure and the presence of asbestos-containing materials, and therefore these provide scope for further research, as these studies also do not rule out the relationship completely. The present study highlights the gaps in current knowledge and indicates areas for further research. Until conclusive evidence based on revised threshold standards and accurate measurement techniques is available, asbestos-containing materials may be considered unsafe for use in non-occupational settings, especially ones that young people and children occupy.}, } @article {pmid37167572, year = {2023}, author = {Hathaway, F and Martins, R and Sorscher, S and Bzura, A and Dudbridge, F and Fennell, DA}, title = {Family Matters: Germline Testing in Thoracic Cancers.}, journal = {American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting}, volume = {43}, number = {}, pages = {e389956}, doi = {10.1200/EDBK_389956}, pmid = {37167572}, issn = {1548-8756}, mesh = {Humans ; *Lung Neoplasms/diagnosis/epidemiology/etiology ; ErbB Receptors/genetics ; *Carcinoma, Non-Small-Cell Lung ; Mutation ; Tumor Suppressor Proteins/genetics/metabolism ; Protein Kinase Inhibitors ; *Mesothelioma ; *Mesothelioma, Malignant ; *Asbestos ; Germ-Line Mutation ; Germ Cells/metabolism ; Genetic Predisposition to Disease ; }, abstract = {Most thoracic cancers arise via a series of stepwise somatic alterations driven by a well-defined carcinogen (ie, tobacco or asbestos for lung cancer and mesothelioma, respectively). A small proportion can emerge on a background of pathogenic germline variants (PGVs), which have the property of heritability. In general, PGVs may be initially suspected on the basis of the presence of specific clinical features. Such gene × environment interactions significantly increase the risk of developing lung cancer (1.5- to 3.2-fold). PGVs have been discovered involving the actionable driver oncogene, epidermal growth factor receptor (EGFR), with an EGFR T790M PGV rate of 0.3%-0.9% in the nonsquamous non-small-cell lung cancer subtype. Its appearance during routine somatic DNA sequencing in those patients who have not had a previous tyrosine kinase inhibitor should raise suspicion. In patients with sporadic mesothelioma, BAP1 is the most frequently mutated tumor driver, with a PGV rate between 2.8% and 8%, associated with a favorable prognosis. BAP1 PGVs accelerate mesothelioma tumorigenesis after asbestos exposure in preclinical models and may be partly predicted by clinical criteria. At present, routine germline genetic testing for thoracic cancers is not a standard practice. Expert genetic counseling is, therefore, required for patients who carry a PGV. Ongoing studies aim to better understand the natural history of patients harboring PGVs to underpin future cancer prevention, precise counseling, and cancer management with the goal of improving the quality and length of life.}, } @article {pmid37165917, year = {2023}, author = {Sato, T and Akao, K and Sato, A and Tsujimura, T and Mukai, S and Sekido, Y}, title = {Aberrant expression of NPPB through YAP1 and TAZ activation in mesothelioma with Hippo pathway gene alterations.}, journal = {Cancer medicine}, volume = {12}, number = {12}, pages = {13586-13598}, pmid = {37165917}, issn = {2045-7634}, mesh = {Humans ; Hippo Signaling Pathway ; *Mesothelioma, Malignant ; *Mesothelioma/genetics ; *Pleural Effusion ; Protein Serine-Threonine Kinases/genetics/metabolism ; Tumor Suppressor Proteins/metabolism ; }, abstract = {BACKGROUND: Mesothelioma is a neoplastic disease associated with asbestos exposure. It is highly malignant and has a poor prognosis; thus, early detection is desirable. Recent whole-genome analysis has revealed that mesothelioma is characterized by a high frequency of mutations in a set of genes involved in the Hippo pathway, such as NF2 and LATS2. However, a rapid, simple, and precise method for finding mesothelioma with these mutations has not yet been established.

METHODS: Clustering of Hippo pathway gene alteration groups and the differential expression of each gene in mesothelioma patients were analyzed using The Cancer Genome Atlas database. Gene expression levels in various tumors and normal tissues were analyzed using public databases. Knockdown or transient expression of YAP1 or TAZ was performed to evaluate the regulation of gene expression by these genes. NT-proBNP was measured in the pleural effusions of 18 patients and was compared with NF2 expression in five cases where cell lines had been successfully established.

RESULTS: NPPB mRNA expression was markedly higher in the group of mesothelioma patients with Hippo pathway gene mutations than in the group without them. NPPB expression was low in all normal tissues except heart, and was highest in mesothelioma. Mesothelioma patients in the high NPPB expression group had a significantly worse prognosis than those in the low NPPB expression group. NPPB expression was suppressed by knockdown of YAP1 or TAZ. NT-proBNP was abundant in the effusions of mesothelioma patients and was particularly high in those with impaired NF2 expression.

CONCLUSIONS: NPPB, whose levels can be measured in pleural effusions of mesothelioma patients, has the potential to act as a biomarker to detect NF2-Hippo pathway gene alterations and/or predict patient prognosis. Additionally, it may provide useful molecular insights for a better understanding of mesothelioma pathogenesis and for the development of novel therapies.}, } @article {pmid37158685, year = {2023}, author = {Moline, J}, title = {Response to the Letter to the Editor From Jeffrey Brent, MD, PhD. Re: Mesothelioma Associated With the Use of Cosmetic Talc.}, journal = {Journal of occupational and environmental medicine}, volume = {65}, number = {5}, pages = {e361}, doi = {10.1097/JOM.0000000000002840}, pmid = {37158685}, issn = {1536-5948}, mesh = {Humans ; Talc/adverse effects ; *Mesothelioma/chemically induced ; *Mesothelioma, Malignant ; }, } @article {pmid37150820, year = {2023}, author = {Avramescu, ML and Potiszil, C and Kunihiro, T and Okabe, K and Nakamura, E}, title = {An investigation of the internal morphology of asbestos ferruginous bodies: constraining their role in the onset of malignant mesothelioma.}, journal = {Particle and fibre toxicology}, volume = {20}, number = {1}, pages = {19}, pmid = {37150820}, issn = {1743-8977}, mesh = {Animals ; Mice ; *Mesothelioma, Malignant/pathology ; Smoking/adverse effects ; *Asbestos/toxicity/analysis ; Lung ; *Lung Neoplasms/chemically induced/pathology ; *Mesothelioma/chemically induced/pathology ; }, abstract = {BACKGROUND: Asbestos is a fibrous mineral that was widely used in the past. However, asbestos inhalation is associated with an aggressive type of cancer known as malignant mesothelioma (MM). After inhalation, an iron-rich coat forms around the asbestos fibres, together the coat and fibre are termed an "asbestos ferruginous body" (AFB). AFBs are the main features associated with asbestos-induced MM. Whilst several studies have investigated the external morphology of AFBs, none have characterised the internal morphology. Here, cross-sections of multiple AFBs from two smokers and two non-smokers are compared to investigate the effects of smoking on the onset and growth of AFBs. Morphological and chemical observations of AFBs were undertaken by transmission electron microscopy, energy dispersive x-ray spectroscopy and selected area diffraction.

RESULTS: The AFBs of all patients were composed of concentric layers of 2-line or 6-line ferrihydrite, with small spherical features being observed on the outside of the AFBs and within the cross-sections. The spherical components are of a similar size to Fe-rich inclusions found within macrophages from mice injected with asbestos fibres in a previous study. As such, the spherical components composing the AFBs may result from the deposition of Fe-rich inclusions during frustrated phagocytosis. The AFBs were also variable in terms of their Fe, P and Ca abundances, with some layers recording higher Fe concentrations (dense layers), whilst others lower Fe concentrations (porous layers). Furthermore, smokers were found to have smaller and overall denser AFBs than non-smokers.

CONCLUSIONS: The AFBs of smokers and non-smokers show differences in their morphology, indicating they grew in lung environments that experienced disparate conditions. Both the asbestos fibres of smokers and non-smokers were likely subjected to frustrated phagocytosis and accreted mucopolysaccharides, resulting in Fe accumulation and AFB formation. However, smokers' AFBs experienced a more uniform Fe-supply within the lung environment compared to non-smokers, likely due to Fe complexation from cigarette smoke, yielding denser, smaller and more Fe-rich AFBs. Moreover, the lack of any non-ferrihydrite Fe phases in the AFBs may indicate that the ferritin shell was intact, and that ROS may not be the main driver for the onset of MM.}, } @article {pmid37147569, year = {2023}, author = {Liang, Y and Li, C and Liu, Y and Tian, L and Yang, D}, title = {Prognostic role of CD74, CD10 and Ki-67 immunohistochemical expression in patients with diffuse malignant peritoneal mesothelioma: a retrospective study.}, journal = {BMC cancer}, volume = {23}, number = {1}, pages = {406}, pmid = {37147569}, issn = {1471-2407}, support = {2016-304//Cangzhou Finance Bureau/ ; }, mesh = {Humans ; Male ; Female ; Middle Aged ; Prognosis ; Retrospective Studies ; Ki-67 Antigen/metabolism ; *Mesothelioma/pathology ; *Percutaneous Coronary Intervention ; Biomarkers, Tumor/metabolism ; *Mesothelioma, Malignant ; *Peritoneal Neoplasms/drug therapy ; }, abstract = {BACKGROUND: Diagnosis and treatment of diffuse malignant peritoneal mesothelioma (DMPM) are still challenging. The aim of the present study was to explore the correlation between CD74, CD10, Ki-67 and clinicopathological parameters, and identify independent prognostic factors of DMPM.

METHODS: Seventy patients with pathologically proven DMPM were retrospectively reviewed. The expression of CD74, CD10 and Ki-67 in peritoneal tissues was detected by immunohistochemical analysis using standard avidin biotin complex (ABC) immunostaining technique. Kaplan-Meier survival analysis and multivariate Cox regression analyses were performed to assess prognostic factors. The nomogram based on the Cox hazards regression model was established. C-index and calibration curve were performed to evaluate the accuracy of nomogram models.

RESULTS: The median age of DMPM was 62.34 years, and the male-to-female ratio was 1: 1.80. CD74 expression was identified in 52 (74.29%) of 70 specimens, CD10 in 34 (48.57%) specimens, and higher Ki-67 in 33(47.14%) specimens. CD74 was negatively associated with asbestos exposure(r = -0.278), Ki-67(r = -0.251) and TNM stage(r = -0.313). All patients were effectively followed up in the survival analysis. Univariate analysis revealed that PCI, TNM stage, treatment, Ki-67, CD74 and ECOG PS were associated with DMPM prognosis. CD74 (HR = 0.65, 95%Cl:0.46-0.91, P = 0.014), Ki-67(HR = 2.09, 95%Cl:1.18-3.73, P = 0.012),TNM stage (HR = 1.89, 95%Cl:1.16-3.09, P = 0.011), ECOG PS(HR = 2.12, 95%Cl:1.06-4.25, P = 0.034), systemic chemotherapy (HR = 0.41, 95%Cl:0.21-0.82, P = 0.011) and intraperitoneal chemotherapy (HR = 0.34, 95%Cl:0.16-0.71, P = 0.004) were independent predictors by multivariate Cox analysis. The C‑index of the nomogram for predicting overall survival (OS) was 0.81. The OS calibration curve showed good agreement between nomogram-predicted and observed survival.

CONCLUSIONS: CD74, Ki-67, TNM stage, ECOG PS and treatment were independent factors affecting prognosis of DMPM. Reasonable chemotherapy treatment might improve the prognosis of patients. The proposed nomogram was a visual tool to effectively predict the OS of DMPM patients.}, } @article {pmid37147272, year = {2023}, author = {Yang, D and Chen, C and Xia, H and Chen, J and Yu, M}, title = {Characteristics of transcription profile, adhesion and migration of SETD2-loss Met-5A mesothelial cells exposed with crocidolite.}, journal = {Journal of applied toxicology : JAT}, volume = {43}, number = {10}, pages = {1511-1521}, doi = {10.1002/jat.4493}, pmid = {37147272}, issn = {1099-1263}, mesh = {Humans ; Asbestos, Crocidolite/toxicity/metabolism ; Epithelium ; *Asbestos/toxicity ; *Mesothelioma ; Silicates ; Cell Adhesion Molecule-1/metabolism ; }, abstract = {Asbestos is a fibrous silicate mineral exhibiting biopersistence and carcinogenic properties and contributes to mesothelioma. Despite the concept of gene-environmental interaction in pathogenesis of mesothelioma, the possible pathophysiological changes of mesothelial cells simultaneously with SET domain containing 2 (SETD2) loss and asbestos exposure remains obscure. Herein, CRISPR/Cas9-mediated SETD2 knockout Met-5A mesothelial cells (Met-5A[SETD2-KO]) were established and exposed with crocidolite, an amphibole asbestos. Cell viability of Met-5A[SETD2-KO] appeared to dramatically decrease with ≥2.5 μg/cm[2] crocidolite exposure as compared with Met-5A, although no cytotoxicity and apoptosis changes of Met-5A[SETD2-KO] and Met-5A was evident with 1.25 μg/cm[2] crocidolite exposure for 48 h. RNA sequencing uncovered top 50 differentially expressed genes (DEGs) between 1.25 μg/cm[2] crocidolite exposed Met-5A[SETD2-KO] (Cro-Met-5A[SETD2-KO]) and 1.25 μg/cm[2] crocidolite exposed Met-5A (Cro-Met-5A), and ITGA4, THBS2, MYL7, RAC2, CADM1, and CLDN11 appeared to be the primary DEGs involved with adhesion in gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Cro-Met-5A[SETD2-KO] had strong migration but mild adhesion behavior as compared with Cro-Met-5A. Additionally, crocidolite tended to increase migration of Met-5A[SETD2-KO] but inhibited migration of Met-5A when compared with their corresponding cells without crocidolite exposure, although no further adhesion property changes was evident for both cells in response to crocidolite. Therefore, crocidolite may affect adhesion-related gene expression and modify adhesion and migration behavior for SETD2-depleted Met-5A, which could provide preliminary insight regarding the potential role of SETD2 in the cell behavior of asbestos-related malignant mesothelial cell.}, } @article {pmid37146474, year = {2023}, author = {Tada, A and Minami, T and Kitai, H and Higashiguchi, Y and Tokuda, M and Higashiyama, T and Negi, Y and Horio, D and Nakajima, Y and Otsuki, T and Mikami, K and Takahashi, R and Nakamura, A and Kitajima, K and Ohmuraya, M and Kuribayashi, K and Kijima, T}, title = {Combination therapy with anti-programmed cell death 1 antibody plus angiokinase inhibitor exerts synergistic antitumor effect against malignant mesothelioma via tumor microenvironment modulation.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {180}, number = {}, pages = {107219}, doi = {10.1016/j.lungcan.2023.107219}, pmid = {37146474}, issn = {1872-8332}, mesh = {Humans ; Female ; Animals ; Mice ; Cell Line, Tumor ; Mice, Inbred C57BL ; *Mesothelioma, Malignant/drug therapy ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; *Indoles/therapeutic use ; *Programmed Cell Death 1 Receptor/antagonists & inhibitors ; *Protein Kinase Inhibitors/therapeutic use ; *Angiogenesis Inhibitors/therapeutic use ; *Antibodies, Monoclonal/therapeutic use ; Allografts ; }, abstract = {Malignant pleural mesothelioma (MPM) is an asbestos-related fatal malignant neoplasm. Although there has been no reliable chemotherapeutic regimen other than combination therapy of cisplatin and pemetrexed for two decades, combination of ipilimumab plus nivolumab brought about a better outcome in patients with MPM. Thus, cancer immunotherapy using immune checkpoint inhibitor (ICI) is expected to play a central role in the treatment of MPM. To maximize the antitumor effect of ICI, we evaluated whether nintedanib, an antiangiogenic agent, could augment the antitumor effect of anti-programmed cell death 1 (PD-1) antibody (Ab). Although nintedanib could not inhibit the proliferation of mesothelioma cells in vitro, it significantly suppressed the growth of mesothelioma allografts in mice. Moreover, combination therapy with anti-PD-1 Ab plus nintedanib reduced tumor burden more dramatically compared with nintedanib monotherapy via inducing remarkable necrosis in MPM allografts. Nintedanib did not promote the infiltration of CD8[+] T cells within the tumor when used alone or in combination with anti-PD-1 Ab but it independently decreased the infiltration of tumor-associated macrophages (TAMs). Moreover, immunohistochemical analysis and ex vivo study using bone marrow-derived macrophages (BMDMs) showed that nintedanib could polarize TAMs from M2 to M1 phenotype. These results indicated that nintedanib had a potential to suppress protumor activity of TAMs both numerically and functionally. On the other hand, ex vivo study revealed that nintedanib upregulated the expression of PD-1 and PD-ligand 1 (PD-L1) in BMDMs and mesothelioma cells, respectively, and exhibited the impairment of phagocytic activity of BMDMs against mesothelioma cells. Co-administration of anti-PD-1 Ab may reactivate phagocytic activity of BMDMs by disrupting nintedanib-induced immunosuppressive signal via binding between PD-1 on BMDMs and PD-L1 on mesothelioma cells. Collectively, combination therapy of anti-PD-1 Ab plus nintedanib enhances the antitumor activity compared with respective monotherapy and can become a novel therapeutic option for patients with MPM.}, } @article {pmid37146029, year = {2023}, author = {Orozco Morales, ML and Rinaldi, CA and de Jong, E and Lansley, SM and Lee, YCG and Zemek, RM and Bosco, A and Lake, RA and Lesterhuis, WJ}, title = {Geldanamycin treatment does not result in anti-cancer activity in a preclinical model of orthotopic mesothelioma.}, journal = {PloS one}, volume = {18}, number = {5}, pages = {e0274364}, pmid = {37146029}, issn = {1932-6203}, mesh = {Humans ; *Mesothelioma, Malignant ; *Mesothelioma/drug therapy/genetics ; *Pleural Neoplasms/pathology ; Cell Proliferation ; *Lung Neoplasms/drug therapy/genetics/pathology ; }, abstract = {Mesothelioma is characterised by its aggressive invasive behaviour, affecting the surrounding tissues of the pleura or peritoneum. We compared an invasive pleural model with a non-invasive subcutaneous model of mesothelioma and performed transcriptomic analyses on the tumour samples. Invasive pleural tumours were characterised by a transcriptomic signature enriched for genes associated with MEF2C and MYOCD signaling, muscle differentiation and myogenesis. Further analysis using the CMap and LINCS databases identified geldanamycin as a potential antagonist of this signature, so we evaluated its potential in vitro and in vivo. Nanomolar concentrations of geldanamycin significantly reduced cell growth, invasion, and migration in vitro. However, administration of geldanamycin in vivo did not result in significant anti-cancer activity. Our findings show that myogenesis and muscle differentiation pathways are upregulated in pleural mesothelioma which may be related to the invasive behaviour. However, geldanamycin as a single agent does not appear to be a viable treatment for mesothelioma.}, } @article {pmid37139482, year = {2023}, author = {Ma, GY and Shi, S and Sang, YZ and Wang, P and Zhang, ZG}, title = {High Expression of SMO and GLI1 Genes with Poor Prognosis in Malignant Mesothelioma.}, journal = {BioMed research international}, volume = {2023}, number = {}, pages = {6575194}, pmid = {37139482}, issn = {2314-6141}, mesh = {Humans ; *Mesothelioma, Malignant/genetics ; Zinc Finger Protein GLI1/genetics/metabolism ; Lymphatic Metastasis ; Signal Transduction ; Hedgehog Proteins/genetics ; *Mesothelioma/genetics/pathology ; Prognosis ; RNA, Messenger/genetics ; Biomarkers, Tumor/genetics/metabolism ; Smoothened Receptor/genetics ; }, abstract = {BACKGROUND: To investigate the value of SMO and GLI1 genes in the hedgehog pathway in malignant mesothelioma specimens. Further study on the expression and prognosis of SMO and GLI1 in malignant mesothelioma tissues and the relationship between the two and the molecular mechanisms of mesothelioma immunity and to further investigate the prognostic value of mesothelioma expression.

MATERIALS AND METHODS: Immunohistochemistry and RT-qPCR were applied to detect the expression of SMO and GLI1 proteins and mRNA in biopsy specimens and plasma cavity effusion specimens from malignant mesothelioma (n = 130) and benign mesothelial tissues (n = 50) and to analyze the clinicopathological significance and survival risk factors of SMO and GLI1 protein expression in mesothelioma. The mechanisms of mesothelioma cell expression and immune cell infiltration were investigated using bioinformatics methods.

RESULTS: SMO and GLI1 in mesothelioma tissues detected high concordance between the diagnostic results of mesothelioma biopsy specimens and plasma cavity effusion specimens. The expression levels of SMO and GLI1 protein and mRNA in mesothelioma tissues were higher than those in benign mesothelioma tissues. The expression levels of SMO and GLI1 protein were correlated with the age, site, and asbestos exposure history of patients with mesothelioma. The expression levels of SMO and GLI1 protein were correlated with the expressions of ki67 and p53 (P < 0.05). SMO and GLI1 gene expression levels were negatively correlated with good prognosis in mesothelioma patients (P < 0.05). Cox proportional risk model indicated that protein expressions of invasion, lymph node metastasis, distant metastasis, staging, and genes were independent prognostic factors of mesothelioma. The GEPIA database showed the overall survival rate and the disease-free survival rate of mesothelioma patients in the high SMO and GLI1 expression groups; the UALCAN database analysis showed lower SMO expression levels in mesothelioma patients with more pronounced TP53 mutations (P = 0.001); GLI1 gene expression levels were strongly correlated with lymph node metastasis in mesothelioma patients (P = 0.009). Timer database analysis showed that the mechanism of immune cell infiltration was closely related to SMO and GLI1 expression. The degree of immune cell infiltration was strongly correlated with the prognosis of mesothelioma patients (P < 0.05).

CONCLUSION: The expression levels of both SMO and GLI1 proteins were higher than those of normal mesothelial tissues, and the mRNA expression levels also changed in the same direction. SMO and GLI1 gene expressions in mesothelioma were negatively correlated with age, site of occurrence, and history of asbestos exposure. Positive expression of SMO and GLI1 was negatively correlated with patient survival. The Cox proportional risk model showed that gender, history of asbestos exposure, site of occurrence, SMO, and GLI1 were independent prognostic factors for mesothelioma. The mechanism of immune cell infiltration in mesothelioma is closely related to the gene expression of both and the survival prognosis of mesothelioma patients.}, } @article {pmid37131285, year = {2023}, author = {Abdelghafar, M and Anand, K and Paiva-Correia, A and Smith, EP and Salle, FG and Joshi, V}, title = {Well-Differentiated Papillary Mesothelial Tumor: An Unusual Radiologic Presentation: A Case Report.}, journal = {Journal of chest surgery}, volume = {56}, number = {3}, pages = {220-223}, pmid = {37131285}, issn = {2765-1606}, abstract = {Well-differentiated papillary mesothelial tumor (WDPMT) is an uncommon tumor, formerly named well-differentiated papillary mesothelioma in the 2015 World Health Organization classification. It has a characteristic papillary architecture, bland cytologic features, a tendency toward superficial spread without invasion, and a good prognosis due to its clinically indolent behavior with prolonged survival. Rare cases with superficial invasion are termed WDPMT with invasive foci. WDPMT occurs primarily in the peritoneum of reproductive-age women, but also rarely in the pleura. We report a case of a 60-year-old woman who developed WDPMT with minimal invasion in the pleura with atypical radiological features and a family history of mesothelioma and indirect asbestos exposure.}, } @article {pmid37128670, year = {2024}, author = {Marshall, T and Lane, J and Lahorra, J}, title = {A Rare Presentation of Minimally Invasive Mesothelioma as a Large Tension Pneumothorax.}, journal = {International journal of surgical pathology}, volume = {32}, number = {1}, pages = {109-114}, doi = {10.1177/10668969231167492}, pmid = {37128670}, issn = {1940-2465}, mesh = {Male ; Humans ; Aged, 80 and over ; *Pneumothorax/diagnosis/etiology/surgery ; *Mesothelioma/complications/diagnosis/surgery ; *Mesothelioma, Malignant/complications ; Pleura/surgery ; *Pleural Effusion/complications ; *Pleural Neoplasms/complications/diagnosis/surgery ; }, abstract = {Development of mesothelioma is associated with asbestos exposure. Common presentations are with pleural-based plaques invading the chest wall and/or pleural effusion on chest imaging. The intent of this case report is to describe a rare presentation of mesothelioma, which presented atypically as a large tension pneumothorax. A 93-year-old male presented with a history of dyspnea that started after a coughing episode. On physical examination he was hemodynamically stable, but was hypoxic requiring 2L of supplemental oxygen. Computed tomography of the chest revealed a large right tension pneumothorax. A chest tube was placed and connected to suction (-20cmH20), but he continued to have an unresolving air leak over the following 2-week period. Upon video-assisted thoracotomy there were no blebs or adhesions seen. Right apical wedge resection and talc pleurodesis were performed. Pathologic examination revealed an atypical mesothelial cell proliferation with minimal, focal invasion into the pulmonary parenchyma. Tumor spread along the visceral pleura was thought to be the underlying cause of the pneumothorax. The surgical margins were uninvolved by the tumor, and the patient was later discharged home in stable condition. This was a rare presentation of what could best be described as minimally invasive mesothelioma arising in a background of probable mesothelioma in situ, which presented atypically as a large tension pneumothorax. This case highlighted the importance of establishing a pathologic diagnosis from pleural effusion cytology and/or pleural biopsy in persons presenting with spontaneous pneumothorax, and the difficulty in confirming a pathologic diagnosis of early mesothelial neoplasia.}, } @article {pmid37104724, year = {2023}, author = {Arrossi, AV}, title = {Pericardial Mesotheliomas.}, journal = {Advances in anatomic pathology}, volume = {30}, number = {4}, pages = {253-258}, doi = {10.1097/PAP.0000000000000399}, pmid = {37104724}, issn = {1533-4031}, mesh = {Humans ; Prospective Studies ; *Mesothelioma, Malignant/complications ; *Mesothelioma/diagnosis/pathology ; *Pleural Neoplasms/diagnosis/etiology/pathology ; *Sarcoma/pathology ; *Heart Neoplasms/diagnosis ; }, abstract = {Primary pericardial mesothelioma (PM) is a rare tumor arising from the mesothelial cells of the pericardium. It has an incidence of <0.05% and comprises <2% of all mesotheliomas; however, it is the most common primary malignancy of the pericardium. PM should be distinguished from secondary involvement by the spread of pleural mesothelioma or metastases, which are more common. Although data are controversial, the association between asbestos exposure and PM is less documented than that with other mesotheliomas. Late clinical presentation is common. Symptoms may be nonspecific but are usually related to pericardial constriction or cardiac tamponade, and diagnosis can be challenging usually requiring multiple imaging modalities. Echocardiography, computed tomography, and cardiac magnetic resonance demonstrate heterogeneously enhancing thickened pericardium, usually encasing the heart, with findings of constrictive physiology. Tissue sampling is essential for diagnosis. Histologically, similar to mesotheliomas elsewhere in the body, PM is classified as epithelioid, sarcomatoid, or biphasic, with the biphasic type being the most common. Combined with morphologic assessment, the use of immunohistochemistry and other ancillary studies is helpful for distinguishing mesotheliomas from benign proliferative processes and other neoplastic processes. The prognosis of PM is poor with about 22% 1-year survival. Unfortunately, the rarity of PM poses limitations for comprehensive and prospective studies to gain further insight into the pathobiology, diagnosis, and treatment of PM.}, } @article {pmid37101434, year = {2022}, author = {Vicari, K and Ribeiro, IM and Aguiar, BF and Brey, C and Boller, S and Miranda, FMD}, title = {Occupational characterization of workers exposed to asbestos: an integrative review.}, journal = {Revista brasileira de medicina do trabalho : publicacao oficial da Associacao Nacional de Medicina do Trabalho-ANAMT}, volume = {20}, number = {4}, pages = {650-658}, pmid = {37101434}, issn = {1679-4435}, abstract = {Asbestos is a mineral fiber abundant in nature and classified as a carcinogen since 1987. The present study aimed to identify, in the scientific literature, what are the occupation and activities developed by sick workers and which categories would be affected with asbestos-related diseases. Through a literature review performed in the following databases: PubMed, CINAHL (Cumulative Index to Nursing and Allied Health Literature), Web of Science, and Regional Portal of the Virtual Health Library, 23 studies published from 2015 to 2020 were selected and evaluated. The occupations that showed greater illness due to exposure to asbestos were general asbestos workers (40%), miners (22%), and textile workers (9%), followed by naval, automotive, carpentry, doll-making, construction, and upholstery workers, as well as workers involved in the rescue, recovery, cleaning, and restoration of the World Trade Center (4%). Of the disease associated with exposure to asbestos, the most described is malignant mesothelioma (43%). Evidence found corroborate pre-existing information in the literature showing that exposure to asbestos may be harmful to health. Moreover, the importance of using personal protective equipment was emphasized, in order to prevent the development of asbestos-related diseases.}, } @article {pmid37095543, year = {2023}, author = {Tomasetti, M and Monaco, F and Strogovets, O and Volpini, L and Valentino, M and Amati, M and Neuzil, J and Santarelli, L}, title = {ATG5 as biomarker for early detection of malignant mesothelioma.}, journal = {BMC research notes}, volume = {16}, number = {1}, pages = {61}, pmid = {37095543}, issn = {1756-0500}, mesh = {Humans ; *Mesothelioma, Malignant ; Mesothelin ; *Mesothelioma/diagnosis ; GPI-Linked Proteins/adverse effects ; *Pleural Neoplasms/diagnosis ; Biomarkers, Tumor/metabolism ; *Asbestos/adverse effects ; *MicroRNAs ; Early Diagnosis ; *Lung Neoplasms/diagnosis ; Autophagy-Related Protein 5 ; }, abstract = {OBJECTIVES: Malignant pleural mesothelioma (MPM) is an aggressive disease with grim prognosis due to lack of effective treatment options. Disease prediction in association with early diagnosis may both contribute to improved MPM survival. Inflammation and autophagy are two processes associated with asbestos-induced transformation. We evaluated the level of two autophagic factors ATG5 and HMGB1, microRNAs (miRNAs) such as miR-126 and miR-222, and the specific biomarker of MPM, soluble mesothelin related proteins (Mesothelin) in asbestos-exposed individuals, MPM patients, and healthy subjects. The performance of these markers in detecting MPM was investigated in pre-diagnostic samples of asbestos-subjects who developed MPM during the follow-up and compared for the three groups.

RESULTS: The ATG5 best distinguished the asbestos-exposed subjects with and without MPM, while miR-126 and Mesothelin were found as a significant prognostic biomarker for MPM. ATG5 has been identified as an asbestos-related biomarker that can help to detect MPM with high sensitivity and specificity in pre-diagnostic samples for up to two years before diagnosis. To utilize this approach practically, higher number of cases has to be tested in order to give the combination of the two markers sufficient statistical power. Performance of the biomarkers should be confirmed by testing their combination in an independent cohort with pre-diagnostic samples.}, } @article {pmid37090283, year = {2023}, author = {Razzak, AN and Syed, A and Procknow, ER and Bequest, A and Jha, P}, title = {Modern Malignant Mesothelioma Manifestation.}, journal = {Cureus}, volume = {15}, number = {3}, pages = {e36479}, pmid = {37090283}, issn = {2168-8184}, abstract = {Malignant pleural mesothelioma (MPM) involves the uncontrolled growth of mesothelial cells that form the lining of pleural serous layers. MPM has been linked with asbestos exposure in mining and manufacturing occupations with an unforgiving prognosis of 4-18 months. In this case report, we present a 56-year-old male with a significant past medical history of hypertension, hyperlipidemia, hepatic steatosis, and ulcerative colitis who presented to the emergency department for worsening cough, eight-pound weight loss over the previous year, night sweats, and fatigue. The patient was admitted due to right pleural effusion with lower lobe collapse seen on imaging; upon diagnostic workup including pleural biopsy, results were consistent with malignant mesothelioma of the epithelioid type. Over the course of six months post-diagnosis, the patient underwent multiple hospital admissions due to acute hypoxic respiratory failure from the segmental left upper lobe and subsegmental right upper lobe pulmonary emboli, recurrent pleural effusion, and anemia. Given the aggressive nature of MPM, the patient was determined not to be a surgical candidate and underwent palliative chemotherapy sessions until his passing. As the patient worked in heating/ventilation/air conditioning with asbestos exposure, taking a full occupational history was crucial. MPM is relatively rare; however, the incidence has increased over the last decade due to tumor development lag time post-asbestos exposure and an increase in do-it-yourself projects. There is no cure for MPM. Multimodal treatment approaches with surgery, chemotherapy, radiotherapy, and immunotherapy have been noted in the literature.}, } @article {pmid37089484, year = {2023}, author = {Marsh, GM and Kruchten, A}, title = {A reevaluation of selected mortality risks in the updated NCI/NIOSH acrylonitrile cohort study.}, journal = {Frontiers in public health}, volume = {11}, number = {}, pages = {1122346}, pmid = {37089484}, issn = {2296-2565}, mesh = {United States/epidemiology ; Humans ; Cohort Studies ; *Acrylonitrile ; National Institute for Occupational Safety and Health, U.S. ; *Occupational Exposure/adverse effects ; *Lung Neoplasms ; *Asbestos ; *Urinary Bladder Neoplasms ; }, abstract = {OBJECTIVES: The study aimed to determine whether the National Cancer Institute's (NCI) recent suggestion of associations between acrylonitrile (AN) exposure and mortality in lung and bladder cancer and pneumonitis is robust to alternative methods of data analysis.

MATERIALS AND METHODS: We used the Richardson method to indirectly adjust risk ratios (RRs) in relation to AN exposure for potential confounding by smoking and asbestos. We repeated key analyses omitting workers from Plant 4 to account for possible local, historical shipyard-related asbestos exposures.

RESULTS: The adjustment of lung cancer RRs for confounding by both smoking and asbestos and omitting Plant 4 workers yielded mostly decreased RRs and much less evidence of a positive association with cumulative AN exposure.

CONCLUSION: Overall, our reanalysis provided little evidence to support NCI's suggestion of associations between AN exposure and mortality in lung and bladder cancer and pneumonitis.}, } @article {pmid37087784, year = {2023}, author = {Barbieri, PG and Consonni, D and Magnani, C and Mensi, C and Mirabell, D and Ricci, P and Terracini, B}, title = {Is mesothelioma related to "initial dose" rather than to "cumulative dose"? Critical remarks on Maghin et al. Assessment protocol of mesothelioma and relevance of SEM-EDS analysis through a case studies of legal medicine of Brescia (Italy). Legal Medicine 2022;57:102076.}, journal = {Legal medicine (Tokyo, Japan)}, volume = {63}, number = {}, pages = {102262}, doi = {10.1016/j.legalmed.2023.102262}, pmid = {37087784}, issn = {1873-4162}, mesh = {Humans ; *Mesothelioma/diagnosis ; *Occupational Exposure ; Forensic Medicine ; Italy ; }, } @article {pmid37081052, year = {2023}, author = {Di Mauro, G and Frontini, F and Torreggiani, E and Iaquinta, MR and Caselli, A and Mazziotta, C and Esposito, V and Mazzoni, E and Libener, R and Grosso, F and Maconi, A and Martini, F and Bononi, I and Tognon, M}, title = {Epigenetic investigation into circulating microRNA 197-3p in sera from patients affected by malignant pleural mesothelioma and workers ex-exposed to asbestos.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {6501}, pmid = {37081052}, issn = {2045-2322}, mesh = {Humans ; *Mesothelioma, Malignant/genetics ; *Circulating MicroRNA ; *Mesothelioma/pathology ; *Lung Neoplasms/pathology ; *Pleural Neoplasms/pathology ; *Asbestos/adverse effects ; *MicroRNAs/genetics ; Epigenesis, Genetic ; }, abstract = {The epigenetic role of microRNAs is established at both physiological and pathological levels. Dysregulated miRNAs and their targets appear to be a promising approach for innovative anticancer therapies. In our previous study, circulating miR-197-3p tested dysregulated in workers ex-exposed to asbestos (WEA). Herein, an epigenetic investigation on this circulating miRNA was carried out in sera from malignant pleural mesothelioma (MPM) patients. MiR-197-3p was quantified in MPM (n = 75) sera and comparatively analyzed to WEA (n = 75) and healthy subject (n = 75) sera, using ddPCR and RT-qPCR techniques. Clinicopathological characteristics, occupational, non-occupational information and overall survival (OS) were evaluated in correlation studies. MiR-197-3p levels, analyzed by ddPCR, were significantly higher in MPM than in WEA cohort, with a mean copies/µl of 981.7 and 525.01, respectively. Consistently, RT-qPCR showed higher miR-197-3p levels in sera from MPM with a mean copies/µl of 603.7, compared to WEA with 336.1 copies/µl. OS data were significantly associated with histologic subtype and pleurectomy. Circulating miR-197-3p is proposed as a new potential biomarker for an early diagnosis of the MPM onset. Indeed, miR-197-3p epigenetic investigations along with chest X-ray, computed tomography scan and spirometry could provide relevant information useful to reach an early and effective diagnosis for MPM.}, } @article {pmid37077094, year = {2023}, author = {Bulutay, P and Vatansever, D and Taskiran, C and Mericoz, CA and Tokat, F and Kapucuoglu, N and Kulac, I}, title = {STRN-ALK rearranged malignant peritoneal mesothelioma-Presenting with bilateral extensive pelvic masses in a young woman: Mimicking low-grade serous ovarian carcinoma.}, journal = {Indian journal of pathology & microbiology}, volume = {66}, number = {2}, pages = {392-395}, doi = {10.4103/ijpm.ijpm_360_21}, pmid = {37077094}, issn = {0974-5130}, mesh = {Adolescent ; Female ; Humans ; Calmodulin-Binding Proteins/genetics ; *Cystadenocarcinoma, Serous/diagnosis/genetics ; Membrane Proteins/genetics ; *Mesothelioma/diagnosis/pathology ; *Mesothelioma, Malignant ; Nerve Tissue Proteins/genetics/metabolism ; *Ovarian Neoplasms/diagnosis/pathology ; Receptor Protein-Tyrosine Kinases/genetics ; *Anaplastic Lymphoma Kinase/genetics ; }, abstract = {Malignant peritoneal mesothelioma (MPM) is an exceptionally rare tumor type. Although some somatic/germline genetic alterations including BAP1 loss have been identified in some cases, the molecular properties of MPMs are remained poorly understood. In recent years, anaplastic lymphoma kinase (ALK) gene rearrangement was revealed in a subset of (3.4%) MPMs. Low-grade serous carcinomas (LGSCs) are a rare subtype of ovarian carcinoma and have some morphologic and immunophenotypic overlapping features with MPMs and this may cause misdiagnosis in daily practice. Here, we report a case of 18-year-old women with STRN-ALK-rearranged MPM and no previous exposure to asbestos. This case was presented with bilateral pelvic masses and histologically was displaying pure papillary morphology with mild-to-moderate nuclear atypia, psammoma bodies, and diffuse PAX8 expression as LGSCs. With the detection of ALK alteration in some of the MPMs, a targeted treatment option has emerged for these unusual tumor types.}, } @article {pmid37062308, year = {2023}, author = {Bolan, S and Kempton, L and McCarthy, T and Wijesekara, H and Piyathilake, U and Jasemizad, T and Padhye, LP and Zhang, T and Rinklebe, J and Wang, H and Kirkham, MB and Siddique, KHM and Bolan, N}, title = {Sustainable management of hazardous asbestos-containing materials: Containment, stabilization and inertization.}, journal = {The Science of the total environment}, volume = {881}, number = {}, pages = {163456}, doi = {10.1016/j.scitotenv.2023.163456}, pmid = {37062308}, issn = {1879-1026}, abstract = {Asbestos is a group of six major silicate minerals that belong to the serpentine and amphibole families, and include chrysotile, amosite, crocidolite, anthophyllite, tremolite and actinolite. Weathering and human disturbance of asbestos-containing materials (ACMs) can lead to the emission of asbestos dust, and the inhalation of respirable asbestos fibrous dust can lead to 'mesothelioma' cancer and other diseases, including the progressive lung disease called 'asbestosis'. There is a considerable legacy of in-situ ACMs in the built environment, and it is not practically or economically possible to safely remove ACMs from the built environment. The aim of the review is to examine the three approaches used for the sustainable management of hazardous ACMs in the built environment: containment, stabilization, and inertization or destruction. Most of the asbestos remaining in the built environment can be contained in a physically secured form so that it does not present a significant health risk of emitting toxic airborne fibres. In settings where safe removal is not practically feasible, stabilization and encapsulation can provide a promising solution, especially in areas where ACMs are exposed to weathering or disturbance. Complete destruction and inertization of asbestos can be achieved by thermal decomposition using plasma and microwave radiation. Bioremediation and chemical treatment (e.g., ultrasound with oxalic acid) have been found to be effective in the inertization of ACMs. Technologies that achieve complete destruction of ACMs are found to be attractive because the treated products can be recycled or safely disposed of in landfills.}, } @article {pmid37058192, year = {2023}, author = {Bardelli, F and Giacobbe, C and Ballirano, P and Borelli, V and Di Benedetto, F and Montegrossi, G and Bellis, D and Pacella, A}, title = {Closing the knowledge gap on the composition of the asbestos bodies.}, journal = {Environmental geochemistry and health}, volume = {45}, number = {7}, pages = {5039-5051}, pmid = {37058192}, issn = {1573-2983}, support = {BRIC2019, ID57//Istituto Nazionale per l'Assicurazione Contro Gli Infortuni sul Lavoro/ ; }, mesh = {Humans ; *Asbestosis/etiology/pathology ; *Asbestos/toxicity/analysis ; Lung/chemistry ; }, abstract = {Asbestos bodies (AB) form in the lungs as a result of a biomineralization process initiated by the alveolar macrophages in the attempt to remove asbestos. During this process, organic and inorganic material deposit on the foreign fibers forming a Fe-rich coating. The AB start to form in months, thus quickly becoming the actual interface between asbestos and the lung tissue. Therefore, revealing their composition, and, in particular, the chemical form of Fe, which is the major component of the AB, is essential to assess their possible role in the pathogenesis of asbestos-related diseases. In this work we report the result of the first x-ray diffraction measurements performed on single AB embedded in the lung tissue samples of former asbestos plant workers. The combination with x-ray absorption spectroscopy data allowed to unambiguously reveal that Fe is present in the AB in the form of two Fe-oxy(hydroxides): ferrihydrite and goethite. The presence of goethite, which can be explained in terms of the transformation of ferrihydrite (a metastable phase) due to the acidic conditions induced by the alveolar macrophages in their attempt to phagocytose the fibers, has toxicological implications that are discussed in the paper.}, } @article {pmid37057081, year = {2023}, author = {Sundaralingam, A and Aujayeb, A and Jackson, KA and Pellas, EI and Khan, II and Chohan, MT and Joosten, R and Boersma, A and Kerkhoff, J and Bielsa, S and Porcel, JM and Rozman, A and Marc-Malovrh, M and Welch, H and Symonds, J and Anevlavis, S and Froudrakis, M and Mei, F and Zuccatosta, L and Gasparini, S and Gonnelli, F and Dhaliwal, I and Mitchell, MA and Fjaellegaard, K and Petersen, JK and Ellayeh, M and Rahman, NM and Burden, T and Bodtger, U and Koegelenberg, CFN and Maskell, NA and Janssen, J and Bhatnagar, R}, title = {Investigation and outcomes in patients with nonspecific pleuritis: results from the International Collaborative Effusion database.}, journal = {ERJ open research}, volume = {9}, number = {2}, pages = {}, pmid = {37057081}, issn = {2312-0541}, abstract = {INTRODUCTION: We present findings from the International Collaborative Effusion database, a European Respiratory Society clinical research collaboration. Nonspecific pleuritis (NSP) is a broad term that describes chronic pleural inflammation. Various aetiologies lead to NSP, which poses a diagnostic challenge for clinicians. A significant proportion of patients with this finding eventually develop a malignant diagnosis.

METHODS: 12 sites across nine countries contributed anonymised data on 187 patients. 175 records were suitable for analysis.

RESULTS: The commonest aetiology for NSP was recorded as idiopathic (80 out of 175, 44%). This was followed by pleural infection (15%), benign asbestos disease (12%), malignancy (6%) and cardiac failure (6%). The malignant diagnoses were predominantly mesothelioma (six out of 175, 3.4%) and lung adenocarcinoma (four out of 175, 2.3%). The median time to malignant diagnosis was 12.2 months (range 0.8-32 months). There was a signal towards greater asbestos exposure in the malignant NSP group compared to the benign group (0.63 versus 0.27, p=0.07). Neither recurrence of effusion requiring further therapeutic intervention nor initial biopsy approach were associated with a false-negative biopsy. A computed tomography finding of a mass lesion was the only imaging feature to demonstrate a significant association (0.18 versus 0.01, p=0.02), although sonographic pleural thickening also suggested an association (0.27 versus 0.09, p=0.09).

DISCUSSION: This is the first multicentre study of NSP and its associated outcomes. While some of our findings are reflected by the established body of literature, other findings have highlighted important areas for future research, not previously studied in NSP.}, } @article {pmid37047661, year = {2023}, author = {Boumya, S and Fallarini, S and Siragusa, S and Petrarolo, G and Aprile, S and Audrito, V and La Motta, C and Garavaglia, S and Moro, L and Pinton, G}, title = {A Selective ALDH1A3 Inhibitor Impairs Mesothelioma 3-D Multicellular Spheroid Growth and Neutrophil Recruitment.}, journal = {International journal of molecular sciences}, volume = {24}, number = {7}, pages = {}, pmid = {37047661}, issn = {1422-0067}, support = {FAR#2019//University of Eastern Piedmont Amadeo Avogadro/ ; MFAG-2021 #26004 to V.A.//Associazione Italiana di Ricerca sul Cancro/ ; }, mesh = {Humans ; Aldehyde Dehydrogenase ; Cell Line, Tumor ; Enzyme Inhibitors/therapeutic use ; *Lung Neoplasms/genetics ; *Mesothelioma/drug therapy/genetics/metabolism ; *Mesothelioma, Malignant ; Neutrophil Infiltration ; *Pleural Neoplasms/pathology ; Spheroids, Cellular/metabolism ; Tumor Microenvironment ; Retinal Dehydrogenase/metabolism ; }, abstract = {Aldehyde dehydrogenase 1A3 (ALDH1A3), one of the three members of the aldehyde dehydrogenase 1A subfamily, has been associated with increased progression and drug resistance in various types of solid tumours. Recently, it has been reported that high ALDH1A3 expression is prognostic of poor survival in patients with malignant pleural mesothelioma (MPM), an asbestos-associated chemoresistant cancer. We treated MPM cells, cultured as multicellular spheroids, with NR6, a potent and highly selective ALDH1A3 inhibitor. Here we report that NR6 treatment caused the accumulation of toxic aldehydes, induced DNA damage, CDKN2A expression and cell growth arrest. We observed that, in CDKN2A proficient cells, NR6 treatment induced IL6 expression, but abolished CXCL8 expression and IL-8 release, preventing both neutrophil recruitment and generation of neutrophil extracellular traps (NETs). Furthermore, we demonstrate that in response to ALDH1A3 inhibition, CDKN2A loss skewed cell fate from senescence to apoptosis. Dissecting the role of ALDH1A3 isoform in MPM cells and tumour microenvironment can open new fronts in the treatment of this cancer.}, } @article {pmid37047331, year = {2023}, author = {Hager, T and Borchert, S and Wessolly, M and Mathilakathu, A and Mairinger, E and Kollmeier, J and Mairinger, T and Hegedus, B and Greimelmaier, K and Wohlschlaeger, J and Herrmann, K and Mairinger, FD}, title = {One Third of Malignant Pleural Mesothelioma Shows High Immunohistochemical Expression of MSLN or CXCR4 Which Indicates Potent Candidates for Endo-Radiotherapy.}, journal = {International journal of molecular sciences}, volume = {24}, number = {7}, pages = {}, pmid = {37047331}, issn = {1422-0067}, mesh = {Humans ; *Mesothelioma, Malignant ; Mesothelin ; *Mesothelioma/drug therapy/radiotherapy/diagnosis ; Positron Emission Tomography Computed Tomography ; GPI-Linked Proteins/genetics/metabolism ; *Pleural Neoplasms/metabolism ; *Lung Neoplasms/metabolism ; Receptors, CXCR4/genetics ; }, abstract = {Malignant pleural mesothelioma (MPM) is a mainly asbestos-related tumour associated with a very poor prognosis. Therapeutic approaches include multimodal therapy and chemotherapeutics, with cisplatin being the drug of choice, but response rates of only up to 14% indicate very poor outcomes. Effective treatment options are lacking. Besides the diagnostic usage of radioligands in positron emission tomography (PET)/computed tomography (CT), the endo-radioligand therapy with Lu177 has been proven as a powerful tool in cancer therapy. Mesothelin (MSLN) and C-XC chemokine receptor 4 (CXCR4) are membrane-bound proteins, expressed in certain cancers, and thus are promising targets for endo-radiotherapy. A significant portion of high MSLN- or CXCR4-expressing tumors within the MPM may open the field for this sophisticated treatment approach in the near future. Formalin-fixed, paraffin-embedded (FFPE) tumour specimens from 105 patients suffering from MPM and treated at the Lung Cancer Centre of Essen and at the Helios Klinikum Emil von Behring Berlin were screened. The tumour samples were arranged in tissue microarrays. We immunohistochemically stained the tumour samples against MSLN and CXCR4. The protein expressions of the stainings were scored by a pathologist by using a semiquantitative method. The data obtained were correlated with the clinical outcome. Overall, 77.1% of the analysed tumours showed CXCR4 protein expression (25.7% of them at high expression level (Score 3)). 48.6% of all samples showed an overall strong staining (Score ≥ 2), 59% of the investigated tumours showed MSLN protein expression (10.5% of them at high expression (Score 3)), and 36.2% of all samples showed an overall strong staining (Score ≥ 2). Our results show significant tissue expression levels, for both CXCR4 and MSLN protein, in a major portion of clinical MPM samples. One-third of patients showed outstanding immunoexpression of at least one of these markers, making them interesting candidates for radioligand-based PET/CT diagnostics and follow-up and furthermore may profit from endo-radiotherapy.}, } @article {pmid37040900, year = {2023}, author = {Chu, GJ and Linton, A and Kao, S and Klebe, S and Adelstein, S and Yeo, D and Rasko, JEJ and Cooper, WA}, title = {High mesothelin expression by immunohistochemistry predicts improved survival in pleural mesothelioma.}, journal = {Histopathology}, volume = {83}, number = {2}, pages = {202-210}, pmid = {37040900}, issn = {1365-2559}, support = {//CSR Ltd/ ; //Li Ka Shing Foundation/ ; //Royal College of Pathologists of Australasia/ ; //Sydney Local Health District/ ; PW18-030//Cancer Council of NSW/ ; RG20-07//Cancer Council of NSW/ ; APP1169460//National Health and Medical Research Council/ ; 1177305//National Health and Medical Research Council/ ; }, mesh = {Humans ; GPI-Linked Proteins/metabolism ; Immunohistochemistry ; *Mesothelioma/pathology ; *Mesothelioma, Malignant ; *Pleural Neoplasms/pathology ; *Receptors, Chimeric Antigen ; }, abstract = {AIMS: Mesothelin (MSLN) is a cancer-associated antigen that is overexpressed in malignancies such as mesothelioma, pancreatic and ovarian cancer. It is also a target for novel personalised therapies, including antibodies, antibody-drug conjugates and chimeric antigen receptor T cells. Immunohistochemistry may predict those who would best respond to anti-mesothelin therapies and guide decisions in therapeutic strategy. This study aimed to assess the intensity and distribution of MSLN immunostaining in mesothelioma, and to determine the prognostic value of MSLN expression by histochemical-score (H-score).

METHODS AND RESULTS: The MN1 anti-MSLN antibody was used to stain a formalin-fixed paraffin-embedded tissue microarray of histologically confirmed mesothelioma from 75 consecutive patients who had undergone pleurectomy with or without decortication. MSLN positivity, the staining intensity, distribution of staining and H-score were evaluated. The correlation of H-score with prognosis was investigated. Sixty-six per cent of epithelioid tumours were MSLN-positive (with expression in > 5% tumour cells). Of MSLN-expressing epithelioid tumours, 70.4% had moderate (2+) or strong (3+) intensity MSLN immunostaining, although only 37% of samples had staining in ≥ 50% of tumour cells. In multivariate analysis, MSLN H-score as a continuous variable and an H-score ≥ 33 were independent predictors of improved survival (P = 0.04 and P < 0.001, respectively).

CONCLUSIONS: MSLN expression was more heterogenous in epithelioid mesothelioma than reported previously. Therefore, it would be appropriate to perform an immunohistochemical assessment of MSLN expression to stratify and assess patient suitability for mesothelin-targeted personalised therapies, such as chimeric antigen receptor T cells.}, } @article {pmid37027032, year = {2023}, author = {Akarsu, M and Ak, G and Dündar, E and Metintaş, M}, title = {Genetic analysis of familial predisposition in the pathogenesis of malignant pleural mesothelioma.}, journal = {Journal of cancer research and clinical oncology}, volume = {149}, number = {10}, pages = {7767-7778}, pmid = {37027032}, issn = {1432-1335}, mesh = {Humans ; *Mesothelioma, Malignant ; Genetic Predisposition to Disease ; *Lung Neoplasms/pathology ; *Mesothelioma/genetics/pathology ; *Asbestos/toxicity ; *Pleural Neoplasms/genetics/pathology ; }, abstract = {PURPOSE: Mesothelioma is the primary tumor of the mesothelial cell membrane. The most important etiology is asbestos exposure. The development of malignant mesothelioma in very few of the population exposed to asbestos and its frequent occurrence in some families may be significant in terms of genetic predisposition. Again, the presence of relatives with mesothelioma who did not have asbestos contact strengthens this argument. This disease, which has limited treatment options and has a poor prognosis, revealing a genetic predisposition, if any, may prolong survival with early diagnosis and effective treatment.

METHODS: Based on the genetic predisposition idea, we diagnosed and followed a total of ten individuals of relatives with mesothelioma. DNA was isolated from peripheral blood and whole genome sequencing analysis was done. Common gene mutations in ten individuals were filtered using bioinformatics. After this filter, from the remaining variants, very rare in the population and damaging mutations are selected.

RESULTS: Eight thousand six hundred and twenty-two common variants have been identified in ten individuals with this analysis. In total, 120 variants were found on 37 genes in 15 chromosomes. These genes are PIK3R4, SLC25A5, ITGB6, PLK2, RAD17, HLA-B, HLA-DRB1, HLA-DQB1, GRM, IL20RA, MAP3K7, RIPK2, and MUC16.

CONCLUSION: Our finding, PIK3R4 gene, is directly associated with mesothelioma development. Twelve genes, which are associated with cancer, were detected in literature. Additional studies, which scan first-degree relatives of individual, are needed to find the specific gene region.}, } @article {pmid37010194, year = {2023}, author = {Kitamura, Y and Zha, L and Liu, R and Shima, M and Nakaya, T and Kurumatani, N and Kumagai, S and Goji, J and Sobue, T}, title = {Association of mesothelioma deaths with neighborhood asbestos exposure due to a large-scale asbestos-cement plant.}, journal = {Cancer science}, volume = {114}, number = {7}, pages = {2973-2985}, pmid = {37010194}, issn = {1349-7006}, support = {15H04774//Japan Society for the Promotion of Science/ ; }, mesh = {Male ; Female ; Humans ; Case-Control Studies ; Environmental Exposure/adverse effects ; *Mesothelioma/chemically induced/epidemiology ; *Asbestos/toxicity ; *Mesothelioma, Malignant/chemically induced ; *Pleural Neoplasms/epidemiology ; }, abstract = {A causal relationship between mesothelioma and occupational asbestos exposure is well known, while some studies have shown a relationship to non-occupational exposures. The aim of this study was to quantify the risk of mesothelioma death associated with neighborhood asbestos exposure due to a large-scale asbestos-cement (AC) plant in Amagasaki, Japan, adjusting properly risk factors including occupational exposures. We conducted a nested case-control study in which a fixed population of 143,929 residents who had been living in Amagasaki City between 1975 and 2002 were followed from 2002 to 2015. All 133 cases and 403 matched controls were interviewed about their occupational, domestic, household, and neighborhood asbestos exposures. Odds ratios (ORs) for mesothelioma death associated with the neighborhood exposure were estimated by a conditional logistic-regression model. For quantitative assessments for neighborhood exposure, we adopted cumulative indices for individuals' residential histories at each residence-specific asbestos concentration multiplied by the duration during the potential exposure period of 1957-1975 (crocidolite). We observed an increasing, dose-dependent risk of mesothelioma death associated with neighborhood exposure, demonstrating that ORs in the highest quintile category were 21.4 (95% confidence interval [CI] 5.8-79.2) for all, 23.7 (95% CI 3.8-147.2) for males, and 26.0 (95% CI 2.8-237.5) for females compared to the lowest quintile, respectively. A quantitative assessment for risk of mesothelioma deaths, adjusting for occupational and non-occupational exposures separately, showed a dose-dependent association with neighborhood exposure and no substantial gender differences in magnitude.}, } @article {pmid36981857, year = {2023}, author = {Gaitens, JM and Culligan, M and Friedberg, JS and Glass, E and Reback, M and Scilla, KA and Sachdeva, A and Atalla, A and McDiarmid, MA}, title = {Laying the Foundation for a Mesothelioma Patient Registry: Development of Data Collection Tools.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {6}, pages = {}, pmid = {36981857}, issn = {1660-4601}, support = {U24 OH009077/OH/NIOSH CDC HHS/United States ; 75D30119P05558/CC/CDC HHS/United States ; }, mesh = {United States/epidemiology ; Humans ; *Mesothelioma/chemically induced ; *Mesothelioma, Malignant ; *Asbestos/toxicity ; *Occupational Exposure/adverse effects ; Registries ; Surveys and Questionnaires ; Incidence ; }, abstract = {Mesothelioma, a cancer of mesothelial cells that line the chest, lungs, heart, and abdomen, is a relatively rare disease. In the United States, approximately 3000 individuals are diagnosed with mesothelioma annually. The primary risk factor for mesothelioma is occupational asbestos exposure which can occur decades prior to disease development, though in approximately 20% of cases, known asbestos exposure is lacking. While several other countries have developed mesothelioma registries to collect key clinical and exposure data elements to allow better estimation of incidence, prevalence, and risk factors associated with disease development, no national mesothelioma registry exists in the U.S. Therefore, as part of a larger feasibility study, a patient exposure questionnaire and a clinical data collection tool were created using a series of key informant interviews. Findings suggest that risk factor and clinical data collection via an on-line questionnaire is feasible, but specific concerns related to confidentiality, in the context of employer responsibility for exposure in the unique U.S. legal environment, and timing of enrollment must be addressed. Lessons learned from piloting these tools will inform the design and implementation of a mesothelioma registry of national scope.}, } @article {pmid36981000, year = {2023}, author = {Doyle, E and Blanchon, D and Wells, S and de Lange, P and Lockhart, P and Waipara, N and Manefield, M and Wallis, S and Berry, TA}, title = {Internal Transcribed Spacer and 16S Amplicon Sequencing Identifies Microbial Species Associated with Asbestos in New Zealand.}, journal = {Genes}, volume = {14}, number = {3}, pages = {}, pmid = {36981000}, issn = {2073-4425}, mesh = {*Siderophores ; New Zealand ; *Asbestos ; Iron/metabolism ; Bacteria/genetics/metabolism ; Soil ; }, abstract = {Inhalation of asbestos fibres can cause lung inflammation and the later development of asbestosis, lung cancer, and mesothelioma, and the use of asbestos is banned in many countries. In most countries, large amounts of asbestos exists within building stock, buried in landfills, and in contaminated soil. Mechanical, thermal, and chemical treatment options do exist, but these are expensive, and they are not effective for contaminated soil, where only small numbers of asbestos fibres may be present in a large volume of soil. Research has been underway for the last 20 years into the potential use of microbial action to remove iron and other metal cations from the surface of asbestos fibres to reduce their toxicity. To access sufficient iron for metabolism, many bacteria and fungi produce organic acids, or iron-chelating siderophores, and in a growing number of experiments these have been found to degrade asbestos fibres in vitro. This paper uses the internal transcribed spacer (ITS) and 16S amplicon sequencing to investigate the fungal and bacterial diversity found on naturally-occurring asbestos minerals, asbestos-containing building materials, and asbestos-contaminated soils with a view to later selectively culturing promising species, screening them for siderophore production, and testing them with asbestos fibres in vitro. After filtering, 895 ITS and 1265 16S amplicon sequencing variants (ASVs) were detected across the 38 samples, corresponding to a range of fungal, bacteria, cyanobacterial, and lichenized fungal species. Samples from Auckland (North Island, New Zealand) asbestos cement, Auckland asbestos-contaminated soils, and raw asbestos rocks from Kahurangi National Park (South Island, New Zealand) were comprised of very different microbial communities. Five of the fungal species detected in this study are known to produce siderophores.}, } @article {pmid36980631, year = {2023}, author = {Mensi, C and Stella, S and Dallari, B and Rugarli, S and Pesatori, AC and Ceresoli, GL and Consonni, D}, title = {Second Primary Cancers in a Population-Based Mesothelioma Registry.}, journal = {Cancers}, volume = {15}, number = {6}, pages = {}, pmid = {36980631}, issn = {2072-6694}, support = {BRiC 55/2019//Istituto Nazionale per l'Assicurazione Contro gli Infortuni sul Lavoro/ ; }, abstract = {BACKGROUND: The presence of a second primary cancer (SPC) in patients with pleural mesothelioma (PM) may impact overall survival and suggest a common mechanism of carcinogenesis or an underlying germline genetic alteration.

METHODS: We evaluated the occurrence of SPCs within PM cases collected from 2000 to 2018 by the Lombardy Mesothelioma Registry and their prognostic implications. Kaplan-Meier analysis was performed to estimate median survival times, together with univariate and multivariate Cox regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) of death.

RESULTS: The median overall survival (OS) of the entire study population (N = 6646) was 10.9 months (95% CI: 10.4-11.2); patient age and histotype were the strongest prognostic factors. No substantial survival difference was observed by the presence of an SPC (10.5 months in 1000 patients with an SPC vs. 10.9 months in 5646 patients in the non-SPC group, HR 1.03, p = 0.40). Shorter OS in the SPC group was only observed in 150 patients with the non-epithelioid subtype (median OS of 5.4 vs. 7.1 months, HR 1.21, p = 0.03).

CONCLUSIONS: The diagnosis of an SPC did not influence the outcome of PM patients in the overall study population but was associated with shorter OS in non-epithelioid cases. Further studies are needed to clarify the role of SPCs as markers of genetic susceptibility in mesothelioma.}, } @article {pmid36974955, year = {2023}, author = {Dement, JM and Loomis, D}, title = {Manufactured doubt and the EPA 2020 chrysotile asbestos risk assessment.}, journal = {American journal of industrial medicine}, volume = {66}, number = {7}, pages = {543-553}, doi = {10.1002/ajim.23476}, pmid = {36974955}, issn = {1097-0274}, mesh = {United States ; Humans ; Asbestos, Serpentine/toxicity/analysis ; United States Environmental Protection Agency ; *Lung Neoplasms ; *Asbestos/toxicity/analysis ; Asbestos, Amphibole/toxicity/analysis ; Asbestos, Crocidolite/analysis/toxicity ; Risk Assessment ; *Mesothelioma/epidemiology ; }, abstract = {While all forms of asbestos have been determined to be carcinogenic to humans by the International Agency for Research on Cancer (IARC) as well as other authoritative bodies, the relative carcinogenic potency of chrysotile continues to be argued, largely in the context of toxic tort litigation. Relatively few epidemiologic studies have investigated only a single form of asbestos; however, one study that included an asbestos textile plant located in Marshville, North Carolina that processed chrysotile asbestos was used by the United States Environmental Protection Agency (EPA) in 2020 to help inform the agency's chrysotile asbestos risk assessment. During the EPA proceedings toxic tort defense consultants submitted comments to the EPA docket and made public presentations asserting that the Marshville plant had processed amphibole asbestos types and should not be used for the chrysotile risk assessment. A detailed evaluation of defense consultant assertions and supporting information and a full assessment of the available information concerning asbestos types used at the Marshville plant was undertaken. The preponderance of evidence continues to support the conclusion that neither amosite nor crocidolite were likely to have been processed in the Marshville textile plant. Defense consultants' assertions about chrysotile use are not supported by the preponderance of evidence and constitute an example of manipulation of information to cast uncertainty and doubt rather than to seek truth and contribute to the body of scientific evidence.}, } @article {pmid36966347, year = {2023}, author = {Marcu, A and McGregor, F and Egan, B and Hill, K and Cook, T and Arber, A}, title = {Developing sustainable patient and public involvement in mesothelioma research: multi-method exploration with researchers, patients, carers, and patient organisations.}, journal = {Research involvement and engagement}, volume = {9}, number = {1}, pages = {15}, pmid = {36966347}, issn = {2056-7529}, support = {JH-18-10//June Hancock Mesothelioma Research Fund/ ; JH-18-10//June Hancock Mesothelioma Research Fund/ ; JH-18-10//June Hancock Mesothelioma Research Fund/ ; JH-18-10//June Hancock Mesothelioma Research Fund/ ; }, abstract = {BACKGROUND: Rare diseases where prognosis is poor provide limited scope for patient and public involvement (PPI). One such disease is mesothelioma, a cancer of the lung pleura or of the peritoneum caused by exposure to asbestos, where PPI is poorly documented. We undertook to explore how PPI could be facilitated in mesothelioma research.

METHODS: An online survey with mesothelioma researchers (n = 23) assessed the perceived benefits and challenges of PPI in mesothelioma. Six online workshops and thirteen in-depth interviews with patients and the public explored their views on how PPI could be increased in mesothelioma and their motivations to become PPI representatives in the future. The survey data were analysed using descriptive statistics and the interviews, using Thematic Analysis.

RESULTS: In the survey, 26% (n = 6) of the researchers did not include PPI in their research, while 74% (n = 17) did, finding it most beneficial at the stages of applying for funding and dissemination. The main perceived benefits of PPI were clarifying the research question and outcome measures, making research more credible and relevant to patients' needs, and increasing its impact. The main perceived challenges to PPI were the general poor prognosis in mesothelioma, and funding timescales which hindered timely recruitment of PPI representatives. The analysis of the interviews with the patients and public revealed three main themes: "Motivations to become a PPI representative in the future", "Understanding the nature of PPI during the project", and "Perceived challenges to PPI in mesothelioma". Altruism and the need for hope were the main reasons to wish to become involved in PPI in the future. For many participants, the project proved to be a journey of understanding the nature of PPI, a concept that was not easy to grasp from the start. The participants perceived certain barriers to PPI such as high symptom burden in mesothelioma, the abstract concept of PPI, and the use of scientific language.

CONCLUSIONS: The present research provides a detailed picture of the benefits and challenges of PPI in mesothelioma. We recommend long-term engagement with mesothelioma support groups so that researchers achieve meaningful and sustainable PPI in mesothelioma research.}, } @article {pmid36965810, year = {2023}, author = {Gao, Y and Mazurek, JM and Li, Y and Blackley, D and Weissman, DN and Burton, SV and Amin, W and Landsittel, D and Becich, MJ and Ye, Y}, title = {Industry, occupation, and exposure history of mesothelioma patients in the U.S. National Mesothelioma Virtual Bank, 2006-2022.}, journal = {Environmental research}, volume = {230}, number = {}, pages = {115085}, pmid = {36965810}, issn = {1096-0953}, support = {CC999999/ImCDC/Intramural CDC HHS/United States ; U24 OH009077/OH/NIOSH CDC HHS/United States ; U24OH009077/ACL/ACL HHS/United States ; }, mesh = {Female ; Humans ; Male ; *Mesothelioma, Malignant/chemically induced ; *Mesothelioma/chemically induced/epidemiology ; *Asbestos/toxicity ; Industry ; Occupations ; *Occupational Exposure/adverse effects ; *Occupational Diseases/epidemiology ; }, abstract = {BACKGROUND: Malignant mesothelioma is associated with environmental and occupational exposure to certain mineral fibers, especially asbestos. This study aims to examine work histories of mesothelioma patients and their survival time.

METHOD: Using the NIOSH Industry and Occupation Computerized Coding System, we mapped occupations and industries recorded for 748 of 1444 patients in the U.S. National Mesothelioma Virtual Bank (NMVB) during the period 2006-2022. Descriptive and survival analyses were conducted.

RESULTS: Among the 1023 industries recorded for those having mesothelioma, the most frequent cases were found for those in manufacturing (n = 225, 22.0%), construction (138, 13.5%), and education services (66, 6.5%); among the 924 occupation records, the most frequent cases were found for those in construction and extraction (174, 18.8%), production (145, 15.7%), and management (84, 9.1%). Males (583) or persons aged >40 years (658) at the time of diagnosis tended to have worked in industries traditionally associated with mesothelioma (e.g., construction), while females (163) or persons aged 20-40 years (27) tended to have worked in industries not traditionally associated with mesothelioma (e.g., health care). Asbestos, unknown substances, and chemical solvents were the most frequently reported exposure, with females most often reporting an unknown substance. A multi-variable Cox Hazard Regression analysis showed that significant prognostic factors associated with decreased survival in mesothelioma cases are sex (male) and work experience in utility-related industry, while factor associated with increased survival are epithelial or epithelioid histological type, prior history of surgery and immunotherapy, and industry experience in accommodation and food services.

CONCLUSION: The NMVB has the potential of serving as a sentinel surveillance mechanism for identifying industries and occupations not traditionally associated with mesothelioma. Results indicate the importance of considering all potential sources of asbestos exposures including occupational, environmental, and extra-occupational exposures when evaluating mesothelioma patients and advising family members.}, } @article {pmid36965809, year = {2023}, author = {Lieberman-Cribbin, W and Taioli, E}, title = {Epidemiologic roadblocks in studying elongated mineral particles and mesothelioma risk.}, journal = {Environmental research}, volume = {230}, number = {}, pages = {115086}, doi = {10.1016/j.envres.2022.115086}, pmid = {36965809}, issn = {1096-0953}, mesh = {Humans ; Silicates ; Iron ; *Occupational Exposure/adverse effects/analysis ; *Air Pollutants, Occupational/analysis ; *Lung Neoplasms/chemically induced/epidemiology ; Minerals/analysis ; *Mesothelioma/chemically induced/epidemiology ; *Asbestos/toxicity ; }, abstract = {Elongated mineral particles (EMPs) are a type of both occupational and environmental exposures that have generated interest in the scientific community due to their potential health effects. Their possible association with mesothelioma represents an area of concern. We provide an overview of the current challenges around epidemiological assessments of EMP exposure and mesothelioma risk, including methodological aspects that need to be addressed when designing and analyzing a study on EMP exposure and mesothelioma. Future work is needed to investigate the relationship between EMPs and mesothelioma, focused on an improved definition of EMP exposure and accounting for other concomitant sources of carcinogen exposure.}, } @article {pmid36965808, year = {2023}, author = {Bogen, KT}, title = {Ultrasensitive dose-response for asbestos cancer risk implied by new inflammation-mutation model.}, journal = {Environmental research}, volume = {230}, number = {}, pages = {115047}, doi = {10.1016/j.envres.2022.115047}, pmid = {36965808}, issn = {1096-0953}, mesh = {Animals ; Humans ; *Asbestos/toxicity ; *Mesothelioma/chemically induced/genetics ; Inflammation/chemically induced/metabolism ; *Lung Neoplasms/chemically induced/genetics ; *Carcinogens, Environmental/toxicity ; Mutation ; }, abstract = {Alterations in complex cellular phenotype each typically involve multistep activation of an ultrasensitive molecular switch (e.g., to adaptively initiate an apoptosis, inflammasome, Nrf2-ARE anti-oxidant, or heat-shock activation pathway) that triggers expression of a suite of target genes while efficiently limiting false-positive switching from a baseline state. Such switches exhibit nonlinear signal-activation relationships. In contrast, a linear no-threshold (LNT) dose-response relationship is expected for damage that accumulates in proportion to dose, as hypothesized for increased risk of cancer in relation to genotoxic dose according to the multistage somatic mutation/clonal-expansion theory of cancer, e.g., as represented in the Moolgavkar-Venzon-Knudsen (MVK) cancer model by a doubly stochastic nonhomogeneous Poisson process. Mesothelioma and lung cancer induced by exposure to carcinogenic (e.g., certain asbestos) fibers in humans and experimental animals are thought to involve modes of action driven by mutations, cytotoxicity-associated inflammation, or both, rendering ambiguous expectations concerning the nature of model-implied shape of the low-dose response for above-background increase in risk of incurring these endpoints. A recent Inflammation Somatic Mutation (ISM) theory of cancer posits instead that tissue-damage-associated inflammation that epigenetically recruits, activates and orchestrates stem cells to engage in tissue repair does not merely promote cancer, but rather is a requisite co-initiator (acting together with as few as two somatic mutations) of the most efficient pathway to any type of cancer in any reparable tissue (Dose-Response 2019; 17(2):1-12). This theory is reviewed, implications of this theory are discussed in relation to mesothelioma and lung cancer associated with chronic asbestos inhalation, one of the two types of ISM-required mutations is here hypothesized to block or impede inflammation resolution (e.g., by doing so for GPCR-mediated signal transduction by one or more endogenous autacoid specialized pro-resolving mediators or SPMs), and supporting evidence for this hypothesis is discussed.}, } @article {pmid36965804, year = {2023}, author = {Sanchez, MS and McGrath-Koerner, M and McNamee, BD}, title = {Characterization of elongate mineral particles including talc, amphiboles, and biopyriboles observed in mineral derived powders: Comparisons of analysis of the same talcum powder samples by two laboratories.}, journal = {Environmental research}, volume = {230}, number = {}, pages = {114791}, doi = {10.1016/j.envres.2022.114791}, pmid = {36965804}, issn = {1096-0953}, mesh = {*Asbestos, Amphibole/toxicity ; Talc/toxicity ; Powders ; Laboratories ; Minerals/toxicity ; *Asbestos ; }, abstract = {Elongate mineral particles, including asbestos, have long been screened in talc and other mineral powders. In recent years, there has been a renewed scrutiny of talc containing asbestos due to allegations in civil litigation in the United States as well as reports, proposals, and white papers by international laboratories and government bodies related to this subject. This study demonstrates the importance of the fundamental understanding of both mineralogy and its application, using microscopy with empirical examples from conflicting analyses of the same talc powders by two independent laboratories in civil litigation in the United States. Methods include polarized light microscopy (PLM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) in the accurate measurement of morphological, optical, compositional, and structural data to characterize mineral-based samples. Discussions in this study include: 1) contrasting the interlaboratory findings of amphibole and amphibole asbestos by PLM and TEM using various preparation techniques, 2) the use of multiple analytical tools on a singular particle for identification, 3) the misidentification of anthophyllite asbestos by inexpert use of electron diffraction using TEM, and 4) the misidentification of chrysotile in talc by PLM. These examples emphasize the importance of not only maintaining the existing requirements, but of the need for even more rigorous analytical requirements in routine monitoring of elongate mineral particles that may occur in mineral-based powders.}, } @article {pmid36965802, year = {2023}, author = {Darnton, L}, title = {Quantitative assessment of mesothelioma and lung cancer risk based on Phase Contrast Microscopy (PCM) estimates of fibre exposure: an update of 2000 asbestos cohort data.}, journal = {Environmental research}, volume = {230}, number = {}, pages = {114753}, doi = {10.1016/j.envres.2022.114753}, pmid = {36965802}, issn = {1096-0953}, mesh = {Humans ; Asbestos, Serpentine/toxicity ; Asbestos, Amosite ; Asbestos, Crocidolite/toxicity ; Microscopy, Phase-Contrast ; *Occupational Exposure ; *Asbestos/toxicity ; *Mesothelioma/chemically induced/epidemiology ; *Lung Neoplasms/chemically induced/epidemiology ; Asbestos, Amphibole/toxicity ; *Occupational Diseases ; }, abstract = {An earlier meta-analysis of mortality studies of asbestos-exposed worker populations, quantified excess mesothelioma and lung cancer risks in relation to cumulative exposure to the three main commercial asbestos types. The aim of this paper was to update these analyses incorporating new data based on increased follow-up of studies previously included, as well as studies of worker populations exposed predominantly to single fibre types published since the original analysis. Mesothelioma as a percentage of expected mortality due to all causes of death, percentage excess lung cancer and mean cumulative exposure were abstracted from available mortality studies of workers exposed predominantly to single asbestos types. Average excess mesothelioma and lung cancer per unit of cumulative exposure were summarised for groupings of studies by fibre type; models for pleural and peritoneal mesothelioma risk and lung cancer risk in terms of cumulative exposure for the different fibre types were fitted using Poisson regression. The average mesothelioma risks (per cent of total expected mortality) per unit cumulative exposure (f/cc.yr), RM, were 0.51 for crocidolite, 0.12 for amosite, and 0.03 for the Libby mixed amphiboles cohort. Significant heterogeneity was present for cohorts classed as chrysotile, with RM values of 0.01 for chrysotile textiles cohorts and 0.0011 for other chrysotile-exposed cohorts. Average percentage excess lung cancer risks per unit cumulative exposure, RL, were 4.3 for crocidolite and amosite combined, 0.82 for Libby. Very significant heterogeneity was present for chrysotile-exposed cohorts with RL values spanning two orders of magnitude from 0.053 for the Balangero mine to 4.8 for the South Carolina textiles cohort. Best fitting models suggest a non-linear exposure-response in which the peritoneal mesothelioma risk is proportional to approximately the square of cumulative exposure. Pleural mesothelioma and lung cancer risk were proportion to powers of cumulative exposure slightly less than one and slightly higher than one respectively.}, } @article {pmid36965801, year = {2023}, author = {Nel, A}, title = {Carbon nanotube pathogenicity conforms to a unified theory for mesothelioma causation by elongate materials and fibers.}, journal = {Environmental research}, volume = {230}, number = {}, pages = {114580}, doi = {10.1016/j.envres.2022.114580}, pmid = {36965801}, issn = {1096-0953}, mesh = {Humans ; *Nanotubes, Carbon/toxicity ; Virulence ; *Mesothelioma/chemically induced ; *Asbestos/toxicity ; Inflammation/pathology ; }, abstract = {The purpose of this review is to elucidate how dimensional and durability characteristics of high aspect ratio nanomaterials (HARN), including carbon nanotubes (CNT) and metal nanowires (MeNW), contribute to understanding the fiber pathogenicity paradigm (FPP), including by explaining the structure-activity relationships (SAR) of a diverse range of natural and synthetic elongate materials that may or may not contribute to mesothelioma development in the lung. While the FPP was originally developed to explain the critical importance of asbestos and synthetic vitreous fiber length, width, aspect ratio and biopersistence in mesothelioma development, there are a vast number of additional inhalable materials that need to be considered in terms of pathogenic features that may contribute to mesothelioma or lack thereof. Not only does the ability to exert more exact control over the length and biopersistence of HARNs confirm the tenets of the FPP, but could be studied by implementating more appropriate toxicological tools for SAR analysis. This includes experimentation with carefully assembled libraries of CNTs and MeNWs, helping to establish more precise dimensional features for interfering in lymphatic drainage from the parietal pleura, triggering of lysosomal damage, frustrated phagocytosis and generation of chronic inflammation. The evidence includes data that long and rigid, but not short and flexible multi-wall CNTs are capable of generating mesotheliomas in rodents based on an adverse outcome pathway requiring access to pleural cavity, obstruction of pleural stomata, chronic inflammation and transformation of mesothelial cells. In addition to durability and dimensional characteristics, bending stiffness of CNTs is a critical factor in determining the shape and rigidity of pathogenic MWCNTs. While no evidence has been obtained in humans that CNT exposure leads to a mesothelioma outcome, it is important to monitor exposure levels and health effect impacts in workers to prevent adverse health outcomes in humans.}, } @article {pmid36965800, year = {2023}, author = {Roggl, VL and Green, CL and Liu, B and Carney, JM and Glass, CH and Pavlisko, EN}, title = {Chronological trends in the causation of malignant mesothelioma: Fiber burden analysis of 619 cases over four decades.}, journal = {Environmental research}, volume = {230}, number = {}, pages = {114530}, pmid = {36965800}, issn = {1096-0953}, support = {UL1 TR002553/TR/NCATS NIH HHS/United States ; }, mesh = {Female ; Humans ; Male ; Asbestos/toxicity ; Asbestosis/etiology/complications ; Lung/pathology ; *Lung Neoplasms/chemically induced/epidemiology ; *Mesothelioma/chemically induced/epidemiology ; Mesothelioma, Malignant/complications/pathology ; *Occupational Exposure ; }, abstract = {Malignant mesothelioma is a relatively rare malignancy with a strong association with prior asbestos exposure. A percentage of cases is not related to asbestos, and fiber analysis of lung tissue is a useful methodology for identifying idiopathic or spontaneous cases. We have performed fiber analyses in more than 600 cases of mesothelioma over the past four decades and were interested in looking for trends in terms of fiber types and concentrations as well as percentages of cases not related to asbestos. Demographic information was also considered including patient age, gender, and tumor location (pleural vs. peritoneal). The histologic pattern of the tumor and the presence or absence of pleural plaques or asbestosis were noted. Fiber analysis was performed in 619 cases, using the sodium hypochlorite technique for digestion of lung tissue samples. Asbestos bodies were counted by light microscopy (LM) and coated and uncoated fibers by scanning electron microscopy (EM). The results were stratified over four decades. Trends that were observed included increasing patient age, increasing percentage of women, increasing percentage of peritoneal cases, and increasing percentage of epithelial histological type. There was a decreasing trend in the percentage of patients with concomitant asbestosis (p < 0.001). The percentage of cases with an elevated lung asbestos content decreased from 90.5% in the 1980s to 54.1% in the 2010s (p < 0.001). This trend also held when the analysis was limited to 490 cases of pleural mesothelioma in men (91.8% in the 1980s vs. 65.1% in the 2010s). There was a decrease in the median asbestos body count by LM from 1390 asbestos bodies per gram of wet lung in the 1980s to 38 AB/gm in the 2010s. Similar trends were observed for each of the asbestos fiber types as detected by EM. We conclude that there has been a progressive decrease in lung fiber content of mesothelioma patients during the past four decades, with an increasing percentage of cases not related to asbestos and an increase in median patient age.}, } @article {pmid36965799, year = {2023}, author = {Moolgavkar, S and Chang, ET and Luebeck, EG}, title = {Multistage carcinogenesis: Impact of age, genetic, and environmental factors on the incidence of malignant mesothelioma.}, journal = {Environmental research}, volume = {230}, number = {}, pages = {114582}, doi = {10.1016/j.envres.2022.114582}, pmid = {36965799}, issn = {1096-0953}, mesh = {Humans ; *Mesothelioma, Malignant/complications ; Incidence ; *Carcinogens, Environmental/toxicity ; Syndrome ; *Lung Neoplasms/chemically induced/epidemiology ; Genetic Predisposition to Disease ; *Asbestos/toxicity ; Carcinogenesis/chemically induced/genetics ; }, abstract = {The current paradigm of carcinogenesis as a cellular evolutionary process driven by mutations of a few critical driver genes has immediate logical implications for the epidemiology of cancer. These include the impact of age on cancer risk, the role played by inherited tumor predisposition syndromes, and the interaction of genetics and environmental exposures on cancer risk. In this paper, we explore the following logical epidemiological consequences of carcinogenesis as a clonal process of mutation accumulation, with special emphasis on asbestos-related cancers, specifically malignant mesothelioma:1 All cancers, including mesothelioma, can and do occur spontaneously, i.e., in the absence of exposure to any environmental carcinogens. 2. Age is an important determinant of cancer risk, with or without exposure to environmental carcinogens. 3. Genetic tumor predisposition syndromes, such as the BAP1 syndrome, increase enormously the risk of cancer even in the absence of exposure to environmental carcinogens. We illustrate these concepts by applying a multistage clonal expansion model to U.S. Surveillance, Epidemiology, and End Results cancer registry data for pleural and peritoneal malignant mesotheliomas in 1975-2018.}, } @article {pmid36965798, year = {2023}, author = {Wylie, AG and Korchevskiy, AA}, title = {Dimensions of elongate mineral particles and cancer: A review.}, journal = {Environmental research}, volume = {230}, number = {}, pages = {114688}, doi = {10.1016/j.envres.2022.114688}, pmid = {36965798}, issn = {1096-0953}, mesh = {Humans ; Mineral Fibers/toxicity ; Minerals/toxicity/analysis ; *Mesothelioma/chemically induced/epidemiology ; Asbestos, Amphibole ; *Lung Neoplasms/chemically induced/epidemiology ; Carcinogens/analysis ; Dust/analysis ; *Asbestos ; }, abstract = {CONTEXT: Based on a decade-long exploration, dimensions of elongate mineral particles are implicated as a pivotal component of their carcinogenic potency. This paper summarizes current understanding of the discovered relationships and their importance to the protection of public health.

OBJECTIVES: To demonstrate the relationships between cancer risk and dimensions (length, width, and other derivative characteristics) of mineral fibers by comparing the results and conclusions of previously published studies with newly published information.

METHODS: A database including 59 datasets comprising 341,949 records were utilized to characterize dimensions of elongate particles. The descriptive statistics, correlation and regression analysis, combined with Monte Carlo simulation, were used to select dimensional characteristics most relevant for mesothelioma and lung cancer risk prediction.

RESULTS: The highest correlation between mesothelioma potency factor and weight fraction of size categories is achieved for fibers with lengths >5.6 μm and widths ≤0.26 μm (R = 0.94, P < 0.02); no statistically significant potency was found for lengths <5 μm. These results are consistent with early published estimations, though are derived from a different approach. For combinations of amphiboles and chrysotile (with a consideration of a correction factor between mineral classes), the potency factors correlated most highly with a fraction of fibers longer than 5 μm and thinner than 0.2 μm for mesothelioma, and longer than 5 μm and thinner than 0.3 μm for lung cancer. Because the proportion of long, thin particles in asbestiform vs. non-asbestiform dusts is higher, the cancer potencies of the former are predicted at a significantly higher level. The analysis of particle dimensionality in human lung burden demonstrates positive selection for thinner fibers (especially for amosite and crocidolite) and prevailing fraction of asbestiform habit.

CONCLUSION: Dimensions of mineral fibers can be confirmed as one of the main drivers of their carcinogenicity. The width of fibers emerges as a primary potency predictor, and fibers of all widths with lengths shorter than 5 μm seem to be non-impactful for cancer risk. The mineral dust with a fibrous component is primarily carcinogenic if it contains amphibole fibers longer than 5 μm and thinner than 0.25 μm.}, } @article {pmid36965797, year = {2023}, author = {Goodman, JE and Becich, MJ and Bernstein, DM and Case, BW and Mandel, JH and Nel, AE and Nolan, R and Odo, NU and Smith, SR and Taioli, E and Gibbs, G}, title = {Non-asbestiform elongate mineral particles and mesothelioma risk: Human and experimental evidence.}, journal = {Environmental research}, volume = {230}, number = {}, pages = {114578}, pmid = {36965797}, issn = {1096-0953}, support = {P30 CA047904/CA/NCI NIH HHS/United States ; U24 OH009077/OH/NIOSH CDC HHS/United States ; U24OH009077/ACL/ACL HHS/United States ; }, mesh = {Humans ; Epigenesis, Genetic ; *Air Pollutants, Occupational ; *Occupational Exposure ; *Lung Neoplasms/chemically induced/epidemiology ; Minerals/analysis ; *Mesothelioma/chemically induced/epidemiology ; *Asbestos/toxicity ; Tumor Microenvironment ; }, abstract = {The presentations in this session of the Monticello II conference were aimed at summarizing what is known about asbestiform and non-asbestiform elongate mineral particles (EMPs) and mesothelioma risks based on evidence from experimental and epidemiology studies. Dr. Case discussed case reports of mesothelioma over the last several decades. Dr. Taioli indicated that the epidemiology evidence concerning non-asbestiform EMPs is weak or lacking, and that progress would be limited unless mesothelioma registries are established. One exception discussed is that of taconite miners, who are exposed to grunerite. Drs. Mandel and Odo noted that studies of taconite miners in Minnesota have revealed an excess rate of mesothelioma, but the role of non-asbestiform EMPs in this excess incidence of mesothelioma is unclear. Dr. Becich discussed the National Mesothelioma Virtual Bank (NMVB), a virtual mesothelioma patient registry that includes mesothelioma patients' lifetime work histories, exposure histories, biospecimens, proteogenomic information, and imaging data that can be used in epidemiology research on mesothelioma. Dr. Bernstein indicated that there is a strong consensus that long, highly durable respirable asbestiform EMPs have the potential to cause mesothelioma, but there is continued debate concerning the biodurability required, and the dimensions (both length and diameter), the shape, and the dose associated with mesothelioma risk. Finally, Dr. Nel discussed how experimental studies of High Aspect Ratio Engineered Nanomaterials have clarified dimensional and durability features that impact disease risk, the impact of inflammation and oxidative stress on the epigenetic regulation of tumor suppressor genes, and the generation of immune suppressive effects in the mesothelioma tumor microenvironment. The session ended with a discussion of future research needs.}, } @article {pmid36965795, year = {2023}, author = {Chatfield, EJ}, title = {Asbestiform fibers and cleavage Fragments: Conceptual approaches for differentiation in laboratory practice and data analysis.}, journal = {Environmental research}, volume = {230}, number = {}, pages = {114529}, doi = {10.1016/j.envres.2022.114529}, pmid = {36965795}, issn = {1096-0953}, mesh = {Animals ; *Occupational Exposure/analysis ; *Air Pollutants, Occupational/analysis ; Particle Size ; Minerals/analysis ; *Asbestos ; Asbestos, Amphibole ; Dust/analysis ; Data Analysis ; }, abstract = {The respirable fractions from 46 different crushed amphibole samples were separated by water elutriation. The dimensions of approximately 200 elongate mineral particles (EMPs) longer than 5 μm in each of these fractions were measured by transmission electron microscopy (TEM). The data were used to address three questions: 1. Can amphiboles be classified on a scale that represents the level of inhalation hazard they present? 2. Can prismatic amphibole be discriminated from amphibole asbestos on the basis of EMP size distributions and concentration measurements? 3. How do different exposure indices (Phase Contrast Microscopy Equivalent (PCME), Berman & Crump protocol fibers, Chatfield extra-criteria EMPs) compare when applied to these amphibole samples? For each sample, the number of respirable EMPs longer than 5 μm per gram of respirable dust and the number of extra-criteria EMPs per gram of respirable dust were calculated. The number of respirable EMPs longer than 5 μm per gram of respirable dust and the proportion of those with dimensions associated with mesothelioma in animal studies were considered to be contributors to the inhalation hazard presented by amphibole dust. In addition to these concentration measurements, the median EMP width, median aspect ratio and the aspect ratio geometric standard deviation (GSD) were considered to be relevant parameters in discriminating prismatic amphibole from asbestiform amphibole. A plot of the aspect ratio GSD against either the concentration of respirable EMPs per gram of respirable dust, the median aspect ratio or the median width allowed discrimination. The data showed a close correspondence between exposures in terms of Chatfield extra-criteria EMPs and Berman and Crump protocol structures for all of the amphibole samples. However, although for commercial asbestos varieties exposures in terms of PCME fibers were comparable to those of the other two metrics, they greatly exceeded those for non-asbestiform amphiboles.}, } @article {pmid36965793, year = {2023}, author = {Cox, LA and Bogen, KT and Conolly, R and Graham, U and Moolgavkar, S and Oberdörster, G and Roggli, VL and Turci, F and Mossman, B}, title = {Mechanisms and shapes of causal exposure-response functions for asbestos in mesotheliomas and lung cancers.}, journal = {Environmental research}, volume = {230}, number = {}, pages = {115607}, doi = {10.1016/j.envres.2023.115607}, pmid = {36965793}, issn = {1096-0953}, mesh = {Humans ; *Asbestos/toxicity ; *Mesothelioma/chemically induced/epidemiology ; *Lung Neoplasms/chemically induced/epidemiology ; Lung/pathology ; Asbestos, Amphibole/toxicity ; Inflammation/metabolism ; }, abstract = {This paper summarizes recent insights into causal biological mechanisms underlying the carcinogenicity of asbestos. It addresses their implications for the shapes of exposure-response curves and considers recent epidemiologic trends in malignant mesotheliomas (MMs) and lung fiber burden studies. Since the commercial amphiboles crocidolite and amosite pose the highest risk of MMs and contain high levels of iron, endogenous and exogenous pathways of iron injury and repair are discussed. Some practical implications of recent developments are that: (1) Asbestos-cancer exposure-response relationships should be expected to have non-zero background rates; (2) Evidence from inflammation biology and other sources suggests that there are exposure concentration thresholds below which exposures do not increase inflammasome-mediated inflammation or resulting inflammation-mediated cancer risks above background risk rates; and (3) The size of the suggested exposure concentration threshold depends on both the detailed time patterns of exposure on a time scale of hours to days and also on the composition of asbestos fibers in terms of their physiochemical properties. These conclusions are supported by complementary strands of evidence including biomathematical modeling, cell biology and biochemistry of asbestos-cell interactions in vitro and in vivo, lung fiber burden analyses and epidemiology showing trends in human exposures and MM rates.}, } @article {pmid36965792, year = {2023}, author = {Smith, SR}, title = {An updated review of diffuse mesothelioma of the pleura - A sentinel health event of potential elongate mineral particle pathogenicity.}, journal = {Environmental research}, volume = {230}, number = {}, pages = {115608}, doi = {10.1016/j.envres.2023.115608}, pmid = {36965792}, issn = {1096-0953}, mesh = {Humans ; Asbestos/toxicity ; Asbestos, Amphibole/toxicity ; *Lung Neoplasms/epidemiology ; *Mesothelioma/chemically induced/epidemiology ; Minerals/adverse effects ; *Occupational Exposure/adverse effects ; Particle Size ; Particulate Matter/adverse effects ; Pleura ; Sentinel Surveillance ; Virulence ; }, abstract = {There are approximately 400 inorganic minerals in the Earth's crust, some of which can be encountered as elongate mineral particles [EMPs] with dimensional characteristics similar to the six minerals known as asbestos and other asbestiform amphiboles with established human pathogenicity. In addition, the rapidly developing field of nanotechnology is producing an ever-increasing array of high aspect ratio engineered nanomaterials [HARNs] with physical dimensions and biodurability similar to the asbestos fiber types with recognized pathogenic potential. Many of these non-asbestos/non-asbestiform EMPs and HARNs with the potential for aerosolization into the breathing zones of workers and in individuals in non-occupational environments have not yet been thoroughly studied with respect to their potential human pathogenicity, a fact which obviously poses concerns for both occupational health and public health professionals. On the basis of dose-response considerations it seems reasonable to infer that if any of these non-regulated EMPs or HARNs actually are pathogenic, then those mineral fiber exposure-induced disorders associated with the lowest cumulative exposure doses of the commercial amphibole types of asbestos, that is, diffuse mesothelioma of the pleura, and its non-malignant correlate of benign parietal pleural plaques, are those which are most likely to occur following inhalational exposures to any of the non-regulated EMPs and HARNs. Because of that observation, this paper reviews certain aspects of diffuse mesothelioma, including a summary of recent changes in the nomenclature of diffuse mesothelioma of the pleura; of both the descriptive and the analytical epidemiology of the disease; of the etiologies of mesothelioma, both "exposure" related and endogenous in nature; and of the asbestos population attributable fraction for diffuse mesotheliomas in the USA, both historically and in the future.}, } @article {pmid36944283, year = {2023}, author = {Belcaid, L and Bertelsen, B and Wadt, K and Tuxen, I and Spanggaard, I and Højgaard, M and Benn Sørensen, J and Ravn, J and Lassen, U and Cilius Nielsen, F and Rohrberg, K and Westmose Yde, C}, title = {New pathogenic germline variants identified in mesothelioma.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {179}, number = {}, pages = {107172}, doi = {10.1016/j.lungcan.2023.03.008}, pmid = {36944283}, issn = {1872-8332}, mesh = {Humans ; Genetic Predisposition to Disease ; *Lung Neoplasms/genetics ; *Mesothelioma/genetics ; *Mesothelioma, Malignant ; Germ-Line Mutation ; Germ Cells ; DNA Helicases/genetics ; }, abstract = {BACKGROUND: Mesothelioma (MM) is associated with asbestos exposure, tumor heterogeneity and aggressive clinical behavior. Identification of germline pathogenic variants (PVs) in mesothelioma is relevant for identifying potential actionable targets and genetic counseling.

METHODS: 44 patients underwent whole exome sequencing (WES) or whole genome sequencing (WGS). Germline variants were selected according to association with inherited cancer using a 168-gene in silico panel, and variants classified according to ACMG/AMP classification as pathogenic (class 5) or likely pathogenic (class 4).

RESULTS: In total, 16 patients (36%) were found to carry pathogenic or likely pathogenic variants in 13 cancer associated genes (ATM, BAP1, BRCA2, CDKN2A, FANCA, FANCC, FANCD2, FANCM, MUTYH, NBN, RAD51B, SDHA and XPC). The germline PVs occurred in DNA repair pathways, including homologous recombination repair (HRR) (75%), nucleotide excision repair (6%), cell cycle regulatory (7%), base excision repair (6%), and hypoxic pathway (6%). Five (31%) patients with a germline PV had a first or second degree relative with mesothelioma compared to none for patients without a germline PV. Previously undiagnosed BRCA2 germline PVs were identified in two patients. Potential actionable targets based on the germline PVs were found in four patients (9%).

CONCLUSION: This study revealed a high frequency of germline PVs in patients with mesothelioma. Furthermore, we identified germline PVs in two genes (NBN & RAD51B) not previously associated with mesothelioma. The data support germline testing in mesothelioma and provide a rationale for additional investigation of the HRR pathway as a potential actionable target.}, } @article {pmid36932968, year = {2023}, author = {Taioli, E and Wolf, A and Alpert, N and Rosenthal, D and Flores, R}, title = {Malignant pleural mesothelioma characteristics and outcomes: A SEER-Medicare analysis.}, journal = {Journal of surgical oncology}, volume = {128}, number = {1}, pages = {134-141}, doi = {10.1002/jso.27243}, pmid = {36932968}, issn = {1096-9098}, mesh = {Humans ; Female ; Male ; Aged ; United States/epidemiology ; *Mesothelioma, Malignant ; Medicare ; *Mesothelioma/epidemiology/therapy ; *Pleural Neoplasms/epidemiology/therapy ; Prognosis ; *Lung Neoplasms/epidemiology/therapy ; SEER Program ; }, abstract = {BACKGROUND: Pleural mesothelioma is rare cancer linked to asbestos exposure. Previous research has indicated that female individuals have better survival than male individuals, but this has never been examined in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database.

MATERIALS AND METHODS: Malignant pleural mesothelioma cases diagnosed from 1992 to 2015 were queried from the linked SEER-Medicare database. Multivariable logistic regression was used to assess the clinical and demographic factors associated with sex. A multivariable Cox proportional hazards model and propensity matching methods were used to assess sex differences in overall survival (OS) while accounting for potential confounders.

RESULTS: Among 4201 patients included in the analysis, 3340 (79.5%) were males and 861 (20.5%) females. Females were significantly older, with more epithelial histology than males were, and had significantly better OS, adjusted for confounders (adjusted hazard ratio, 0.83, 95% confidence interval: 0.76-0.90). Other variables independently associated with improved survival included younger age at diagnosis, having a spouse/domestic partner, epithelial histology, lower comorbidity score, and receipt of surgery or chemotherapy.

CONCLUSIONS: The study describes sex differences in mesothelioma occurrence, treatment, and survival and is the first to examine SEER-Medicare. It provides directions for future research into potential therapeutic targets.}, } @article {pmid36924064, year = {2023}, author = {Spaziani, E and Di Filippo, AR and Valle, G and Spaziani, M and Francioni, P and Caruso, G and Tamagnini, GT and Mosciatti, E and Picchio, M and De Cesare, A}, title = {A rare case of primary gastric Burkitt's lymphoma associated with malignant pleural mesothelioma.}, journal = {Annali italiani di chirurgia}, volume = {12}, number = {}, pages = {}, pmid = {36924064}, issn = {2239-253X}, mesh = {Humans ; Male ; Aged ; *Mesothelioma, Malignant/complications ; *Burkitt Lymphoma/complications/diagnosis ; *Mesothelioma/complications/diagnosis/pathology ; *Pleural Neoplasms/complications/diagnosis/pathology ; *Pleural Effusion ; *Respiratory Insufficiency/complications ; Dyspnea/complications ; }, abstract = {BACKGROUND: Primary gastric Burkitt lymphoma (PG BL) and malignant pleural mesothelioma (MPM) are rare and aggressive tumors with poor prognosis. HIV and EBV infection have a link in the aetiology of PG BL, while MPM is usually associated with asbestos exposure. Endoluminal bleeding from massive solid tumor, and dyspnea usually due to pleural effusion, are the typical clinical manifestations respectively of PG BL and MPM. In most patients just palliative treatment is indicated.

CASE REPORT: A caucasian elderly male, negative for the proven risk factors, presenting respiratory failure due to massive left pleural effusion with severe mediastinal shift. Contrast enhanced - Computed Tomography (CE-CT) showed a large mass causing circumferential thickening of the gastric fundus, infiltrating the left diaphragmatic dome and the ipsilateral crus. Macroscopically, on endoscopy the gastric fundus appeared completely occupied by an ulcerated large mass protunding in the gastric lumen. Histopathological examination from biopsy specimens taken during esophagogastroduodenoscopy and thoracoscopy allowed to make diagnosis of PG BL and MPM. The patient first underwent a placement of a chest tube drainage for the pleural effusion and then a thoracoscopic talc insufflation (TTI) in the left hemithorax. A surgical treatment of the gastric lesion was planned, due to the rapid growth and the high risk of bleeding. The patient died because of fatal cardiac arrhythmia, before undergoig abdominal surgery.

CONCLUSIONS: This report presents an unique case of PG BL associated with MPM and highlights the real challenge for the physicians to identify them in early stage, especially in patients without the proved risk factors. The onset symptoms make it a very singular case, characterized by severe dyspnea up to respiratory failure, due to massive left pleural effusion and contralateral mediastinal fluttering, without an active bleeding from the gastric mass, while CE-CT findings were instead negative for pleural thickening and positive for circumferential thickening of the gastric fundus.

KEY WORDS: Burkitt Lymphoma, Case Report, Gastric, Pleural Mesothelioma, Pleural Effusion, Respiratory Failure.}, } @article {pmid36902544, year = {2023}, author = {Borgeaud, M and Kim, F and Friedlaender, A and Lococo, F and Addeo, A and Minervini, F}, title = {The Evolving Role of Immune-Checkpoint Inhibitors in Malignant Pleural Mesothelioma.}, journal = {Journal of clinical medicine}, volume = {12}, number = {5}, pages = {}, pmid = {36902544}, issn = {2077-0383}, abstract = {Malignant pleural mesothelioma (MPM) is a rare cancer usually caused by asbestos exposure and associated with a very poor prognosis. After more than a decade without new therapeutic options, immune checkpoint inhibitors (ICIs) demonstrated superiority over standard chemotherapy, with improved overall survival in the first and later-line settings. However, a significant proportion of patients still do not derive benefit from ICIs, highlighting the need for new treatment strategies and predictive biomarkers of response. Combinations with chemo-immunotherapy or ICIs and anti-VEGF are currently being evaluated in clinical trials and might change the standard of care in the near future. Alternatively, some non-ICI immunotherapeutic approaches, such as mesothelin targeted CAR-T cells or denditric-cells vaccines, have shown promising results in early phases of trials and are still in development. Finally, immunotherapy with ICIs is also being evaluated in the peri-operative setting, in the minority of patients presenting with resectable disease. The goal of this review is to discuss the current role of immunotherapy in the management of malignant pleural mesothelioma, as well as promising future therapeutic directions.}, } @article {pmid36901302, year = {2023}, author = {Buralli, RJ and Pinheiro, RDC and Susviela, LL and Duracenko, SRC and De Capitani, EM and Savaris, A and Algranti, E}, title = {The Brazilian System for Monitoring Workers and General Population Exposed to Asbestos: Development, Challenges, and Opportunities for Workers' Health Surveillance.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {5}, pages = {}, pmid = {36901302}, issn = {1660-4601}, mesh = {Humans ; *Asbestosis/epidemiology ; Brazil ; Quality of Life ; *Occupational Exposure ; Population Surveillance ; *Asbestos ; *Mesothelioma/epidemiology ; *Lung Neoplasms/epidemiology ; }, abstract = {UNLABELLED: The lack of safe levels of asbestos exposure and the long latency of asbestos-related disease (ARD) makes workers' health surveillance challenging, especially in lower-income countries. This paper aims to present the recently developed Brazilian system for monitoring workers and general population exposed to asbestos (Datamianto), and to discuss the main challenges and opportunities for workers' health surveillance.

METHODS: a descriptive study of the Datamianto development process, examining all the stages of system planning, development, improvement, validation, availability, and training of health services for its use, in addition to presenting the main challenges and opportunities for its implementation.

RESULTS: The system was developed by a group of software developers, workers' health specialists, and practitioners, and it was recently incorporated by the Ministry of Health to be used for workers' health surveillance. It can facilitate the monitoring of exposed individuals, epidemiological data analysis, promote cooperation between health services, and ensure periodical medical screening guaranteed to workers by labor legislation. Moreover, the system has a Business Intelligence (BI) platform to analyze epidemiologic data and produce near real-time reports.

CONCLUSIONS: Datamianto can support and qualify the healthcare and surveillance of asbestos-exposed workers and ARD, promoting a better quality of life for workers and improving companies' compliance with legislation. Even so, the system's significance, applicability, and longevity will depend on the efforts aimed at its implementation and improvement.}, } @article {pmid36900330, year = {2023}, author = {Al Khatib, MO and Pinton, G and Moro, L and Porta, C}, title = {Benefits and Challenges of Inhibiting EZH2 in Malignant Pleural Mesothelioma.}, journal = {Cancers}, volume = {15}, number = {5}, pages = {}, pmid = {36900330}, issn = {2072-6694}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive thoracic cancer that is mainly associated with prior exposure to asbestos fibers. Despite being a rare cancer, its global rate is increasing and the prognosis remains extremely poor. Over the last two decades, despite the constant research of new therapeutic options, the combination chemotherapy with cisplatin and pemetrexed has remained the only first-line therapy for MPM. The recent approval of immune checkpoint blockade (ICB)-based immunotherapy has opened new promising avenues of research. However, MPM is still a fatal cancer with no effective treatments. Enhancer of zeste homolog 2 (EZH2) is a histone methyl transferase that exerts pro-oncogenic and immunomodulatory activities in a variety of tumors. Accordingly, a growing number of studies indicate that EZH2 is also an oncogenic driver in MPM, but its effects on tumor microenvironments are still largely unexplored. This review describes the state-of-the-art of EZH2 in MPM biology and discusses its potential use both as a diagnostic and therapeutic target. We highlight current gaps of knowledge, the filling of which will likely favor the entry of EZH2 inhibitors within the treatment options for MPM patients.}, } @article {pmid36896837, year = {2023}, author = {Scarselli, A and Corfiati, M and Marinaccio, A}, title = {Occupational exposure register-based cohort study on mortality among asbestos-related workers in Italy after the ban.}, journal = {European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP)}, volume = {32}, number = {3}, pages = {281-285}, doi = {10.1097/CEJ.0000000000000786}, pmid = {36896837}, issn = {1473-5709}, mesh = {Male ; Humans ; Cohort Studies ; *Asbestos/toxicity ; *Mesothelioma ; *Occupational Exposure/adverse effects ; Carcinogens ; Italy/epidemiology ; *Lung Neoplasms/etiology ; }, abstract = {OBJECTIVE: Asbestos is a human carcinogen and can cause some types of cancer, including mesothelioma. A relevant number of workers are still engaged in asbestos removal and disposal activities, whose actual risk of asbestos-related diseases is still scarcely recognized. The main objective of this study is to assess the cause-specific mortality among workers involved in asbestos removal and disposal after the ban in Italy.

METHODS: Data from the Information System on Occupational Exposure to carcinogens (SIREP) in the period 1996-2018 were selected. Proportionate mortality ratios (PMRs) by cause of death were calculated by linking exposure occupational information to national mortality statistics (2005-2018), assuming a Poisson distribution of the data.

RESULTS: A total of 142 deaths (all men) were identified among 13 715 asbestos removal and disposal workers. A significant excess (P  < 0.05) of mesothelioma deaths was found among male workers, about five-fold the expected. A significant increase in the mortality ratio was also found for malignant melanoma of skin.

CONCLUSIONS: A risk of mesothelioma has been found among workers involved in asbestos removal and disposal. Epidemiological surveillance and promotion of prevention action plans are highly recommended for workers engaged in asbestos removal and disposal activities, to ensure compliance with regulatory requirements and reduce the still relevant risk of contracting the related tumor pathology.}, } @article {pmid36883200, year = {2023}, author = {Janosikova, M and Nakladalova, M and Stepanek, L}, title = {Current causes of mesothelioma: how has the asbestos ban changed the perspective?.}, journal = {Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia}, volume = {167}, number = {2}, pages = {99-108}, pmid = {36883200}, issn = {1804-7521}, mesh = {Humans ; Female ; Adolescent ; *Nanotubes, Carbon ; *Lung Neoplasms/chemically induced ; *Mesothelioma/chemically induced/complications ; *Mesothelioma, Malignant/chemically induced/complications ; *Asbestos/adverse effects ; Environmental Exposure/adverse effects ; Minerals ; *Pleural Neoplasms/chemically induced/complications ; }, abstract = {The association of mesothelioma, a lethal lung disease, with asbestos has led to an absolute ban on asbestos in at least 55 countries worldwide. The purpose of this paper is to review residual exposure to asbestos as well as other emerging causes of mesothelioma outside asbestos. The review provides detailed description of asbestos minerals, their geographical locations, mesothelioma in these areas, as well as contemporary possible sources of asbestos exposure. Second, we examine other emerging causes of mesothelioma including: ionizing radiation as the second most important risk factor after asbestos, particularly relevant to patients undergoing radiotherapy, third, carbon nanotubes which are under investigation and fourth, Simian virus 40. In the case of asbestos per se, the greatest risk is from occupational exposure during mining and subsequent processing. Of the non-occupational exposures, environmental exposure is most serious, followed by exposure from indoor asbestos minerals and secondary familial exposure. Overall, asbestos is still a major risk factor, but alternative causes should not be neglected, especially in young people, in women and those with a history of radiotherapy or living in high-risk locations.}, } @article {pmid36876393, year = {2023}, author = {Walther, D and Hunziker, S and Boichat Burdy, S and Ruf, F and Rossi, I and Vernez, D}, title = {[Asbestos related cancers: burden and recognition as occupational diseases].}, journal = {Revue medicale suisse}, volume = {19}, number = {816}, pages = {422-425}, doi = {10.53738/REVMED.2023.19.816.422}, pmid = {36876393}, issn = {1660-9379}, mesh = {Humans ; *Asbestos ; Health Personnel ; *Lung Neoplasms ; *Occupational Diseases ; }, abstract = {Although asbestos has been banned in Switzerland since 1989, diseases caused by asbestos are still present and increasing today. In Switzerland, per year, occupational exposure to asbestos is responsible for approximately 135 deaths from mesothelioma and 930 deaths from lung cancer, though the latter is rarely recognized as an occupational disease. Taking an occupational history is essential for all such diagnosis, especially in smokers, whose risk of lung cancer increases due to the synergistic effect of asbestos and tobacco exposure. The medical practitioner can play an important role in occupational diseases being recognized as such, which is essential for the reimbursement of medical expenses by the accident insurance companies and the allocation of indemnities and pensions for the patient or their family.}, } @article {pmid36857650, year = {2023}, author = {Han, J and Park, S and Yon, DK and Lee, SW and Woo, W and Dragioti, E and Koyanagi, A and Jacob, L and Kostev, K and Radua, J and Lee, S and Shin, JI and Smith, L}, title = {Global, Regional, and National Burden of Mesothelioma 1990-2019: A Systematic Analysis of the Global Burden of Disease Study 2019.}, journal = {Annals of the American Thoracic Society}, volume = {20}, number = {7}, pages = {976-983}, doi = {10.1513/AnnalsATS.202209-802OC}, pmid = {36857650}, issn = {2325-6621}, mesh = {Male ; Humans ; Female ; *Global Burden of Disease ; Quality-Adjusted Life Years ; Risk Factors ; Morbidity ; Incidence ; *Mesothelioma/epidemiology ; Global Health ; }, abstract = {Rationale: Mesothelioma has become a major health burden since World War II because of the use of asbestos. Although many countries have imposed bans on asbestos, there remain significant mortality and morbidity from mesothelioma because of its long latent period and aggressiveness. Also, the use of asbestos is increasing in low-income countries, potentiating risk of mesothelioma in the coming decades. Assessment of the global burden of mesothelioma is required to take proper measures against the disease. Objectives: To assess the burden of mesothelioma from 1990 to 2019 at the global, regional, and national levels and to investigate patterns according to sex, age, sociodemographic index, and risk factors. Methods: The numbers, rates, and age-standardized rates of incidence, death, and disability-adjusted life years (DALYs) of mesothelioma in 204 countries and territories from 1990 to 2019 were estimated using vital registration and cancer registry data. The relationship between sociodemographic index and age-standardized DALY rate was determined, and DALYs attributable to occupational exposure to asbestos were calculated. Results: In 2019, there were 34,511 (95% uncertainty interval [UI], 31,199 to 37,771) incident cases of mesothelioma globally, with an age-standardized rate of 0.43 per 100,000 persons (95% UI, 0.38 to 0.47), which decreased between 1990 and 2019 by -12.6% (95% UI, -21.8% to -2.3%). Mesothelioma was responsible for 29,251 (95% UI, 26,668 to 31,006) deaths in 2019, with an age-standardized rate of 0.36 deaths per 100,000 persons (95% UI, 0.33 to 0.39), which decreased between 1990 and 2019 by -9.6% (95% UI, -17.8% to -1.1%). The age-standardized incidence rate increased in central Europe between 1990 and 2019 by 46.1% (95% UI, 16.6% to 72.4%). The Netherlands, Australia, and the United Kingdom had the highest age-standardized incidence rates. Incidence rates were higher in men than in women ages 45-49 to 90-94 years, peaking at 85-89 years. Occupational exposure to asbestos contributed to 85.2% (95% UI, 82.1% to 88.1%) of DALYs. Conclusions: The global burden of mesothelioma is decreasing in terms of age-standardized incidence and mortality rates. Mesothelioma remains a substantial public health challenge in many parts of the world.}, } @article {pmid36833533, year = {2023}, author = {Lai, H and Hu, C and Qu, M and Liu, X and Xue, Y and Xu, P and Hao, D}, title = {Mesothelioma Due to Workplace Exposure: A Comprehensive Bibliometric Analysis of Current Situation and Future Trends.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {4}, pages = {}, pmid = {36833533}, issn = {1660-4601}, mesh = {Humans ; *Mesothelioma, Malignant ; *Mesothelioma ; Workplace ; *Lung Neoplasms ; Bibliometrics ; }, abstract = {Background: This article provides an overview of the current status and research progress of mesothelioma. Methods: A total of 2638 documents published from 1 January 2004 to 30 November 2022 were retrieved from the Web of Science Core Collection and analyzed via Microsoft Office Excel 2019, VOSviewer 1.6.18, and Tableau 2022.2. Results: There was an obvious increase in the number of publications regarding mesothelioma in the last 18 years, with the United States dominating the research field with 715 publications and 23,882 citations, while the University of Turin contributed the most (118). Occupational & Environmental Medicine was the most popular journal (80), with Corrado Magnani being the most prolific author (52) and Michele Carbone obtaining the most citations (4472). "Oncology" and "Health Science of Environment & Occupation" were the two main subjects, while the keywords "asbestos", "lung cancer", "gene expression", "apoptosis", "survival", and "cisplatin" were the most popular. Conclusions: The containment of mesothelioma calls for more participation from low- and middle-income countries, and further attention needs to be paid to clinical research.}, } @article {pmid36831074, year = {2023}, author = {Filetti, V and Lombardo, C and Loreto, C and Dounias, G and Bracci, M and Matera, S and Rapisarda, L and Rapisarda, V and Ledda, C and Vitale, E}, title = {Small RNA-Seq Transcriptome Profiling of Mesothelial and Mesothelioma Cell Lines Revealed microRNA Dysregulation after Exposure to Asbestos-like Fibers.}, journal = {Biomedicines}, volume = {11}, number = {2}, pages = {}, pmid = {36831074}, issn = {2227-9059}, support = {20722142130//University of Catania/ ; }, abstract = {Environmental exposure to fibers of respirable size has been identified as a risk for public health. Experimental evidence has revealed that a variety of fibers, including fluoro-edenite, can develop chronic respiratory diseases and elicit carcinogenic effects in humans. Fluoro-edenite (FE) is a silicate mineral first found in Biancavilla (Sicily, Italy) in 1997. Environmental exposure to its fibers has been correlated with a cluster of malignant pleural mesotheliomas. This neoplasm represents a public health problem due to its long latency and to its aggression not alerted by specific symptoms. Having several biomarkers providing us with data on the health state of those exposed to FE fibers or allowing an early diagnosis on malignant pleural mesothelioma, still asymptomatic patients, would be a remarkable goal. To these purposes, we reported the miRNA transcriptome in human normal mesothelial cell line (MeT-5A) and in the human malignant mesothelioma cell line (JU77) exposed and not exposed to FE fibers. The results showed a difference in the number of deregulated miRNAs between tumor and nontumor samples both exposed and not exposed to FE fibers. As a matter of fact, the effect of exposure to FE fibers is more evident in the expression of miRNA in the tumor samples than in the nontumor samples. In the present paper, several pathways involved in the pathogenesis of malignant pleural mesothelioma have been analyzed. We especially noticed the involvement of pathways that have important functions in inflammatory processes, angiogenesis, apoptosis, and necrosis. Besides this amount of data, further studies will be designed for the selection of the most significant miRNAs to test and validate their diagnostic potential, alone or in combination with other protein biomarkers, in high-risk individuals' liquid biopsy to have a noninvasive tool of diagnosis for this neoplasm.}, } @article {pmid36825373, year = {2023}, author = {Zona, A and Fazzo, L and Benedetti, M and Bruno, C and Vecchi, S and Pasetto, R and Minichilli, F and De Santis, M and Nannavecchia, AM and Di Fonzo, D and Contiero, P and Ricci, P and Bisceglia, L and Manno, V and Minelli, G and Santoro, M and Gorini, F and Ancona, C and Scondotto, S and Soggiu, ME and Scaini, F and Beccaloni, E and Marsili, D and Villa, MF and Maifredi, G and Magoni, M and Iavarone, I and , }, title = {[SENTIERI - Epidemiological Study of Residents in National Priority Contaminated Sites. Sixth Report].}, journal = {Epidemiologia e prevenzione}, volume = {47}, number = {1-2 Suppl 1}, pages = {1-286}, doi = {10.19191/EP23.1-2-S1.003}, pmid = {36825373}, issn = {1120-9763}, mesh = {Pregnancy ; Adolescent ; Young Adult ; Humans ; Female ; Male ; Child ; Adult ; Middle Aged ; Aged ; Infant, Newborn ; Infant ; Child, Preschool ; *Stomach Neoplasms/complications ; Cross-Sectional Studies ; Italy/epidemiology ; *Mesothelioma/etiology ; *Asbestos ; *Breast Neoplasms ; *Lymphoma, Non-Hodgkin ; *Lung Neoplasms/epidemiology ; *Urinary Bladder Neoplasms/complications ; *Liver Neoplasms ; *Colorectal Neoplasms ; }, abstract = {INTRODUCTION ADN OBJECTIVES: The Sixth Report presents the results of the "SENTIERI Project: implementation of the permanent epidemiological surveillance system of populations residing in Italian Sites of Remediation Interest", promoted and financed by the Italian Ministry of Health (Centre for Disease Control and Prevention - CCM Project 2018). The aim of this study is to update the mortality and hospitalization analyses concerning the 6,227,531 inhabitants (10.4% of the Italian population) residing in 46 contaminated sites (39 of national interest and 7 of regional interest). The sites include 316 municipalities distributed as follows: 15 in the North-East (20.3% of the investigated population); 104 in the North-West (12% of the investigated population), 32 in the Centre (12.6% of the investigated population), 165 in the South and Islands (55.5% of the investigated population). Analyses were carried out on the paediatric-adolescent (1,128,396 residents) and youth (665,284 residents) population, and a study on congenital anomalies (CA) was carried out at sites covered by congenital malformation registers. Accompanying the epidemiological assessments, site-specific socioeconomic conditions were examined and an overall estimate of excess risk for populations residing at contaminated sites was drawn up. By means of a systematic review of the scientific literature, the epidemiological evidence on causal links between sources of environmental exposure and health effects was updated to identify pathologies of a priori interest.

METHODOLOGY: In the 46 sites included in the SENTIERI Project, mortality (time window: 2013-2017) and hospital admissions (time window: 2014-2018) of the general population of all ages, divided by gender, and of the paediatric-adolescent (0-1 year, 0-14 years, 0-19 years), youth (20-29 years), and overall (0-29 years) age groups, divided by gender, were analysed. In 21 sites, CA diagnosed within the first year of life were studied. Standardised mortality ratios (SMR) and hospitalization ratios (SHR) were calculated with reference to the rates in the regions to which the sites belong. The reference population was calculated net of residents in the sites. CA were studied by calculating the prevalence per 10,000 births and the ratio, multiplied by 100, between the cases observed at the site and those expected on the basis of the prevalences observed in the reference area (region or sub-regional area of belonging, according to the geographical coverage of the registry). The socioeconomic condition studied in the 46 sites is based on the convergence of three deprivation indicators with respect to the reference region: deprivation index at municipal level, deprivation index at census section level, premature mortality indicator (age range 30-69 years) for chronic non-communicable diseases. For the estimation of excess risk for the entire study population, meta-analysis of the mortality and hospitalization risk estimates for each site was carried out and the number of excess deaths estimated for the sites as a whole. The epidemiological evidence was updated through a systematic literature review (January 2009-May 2020), following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The search was carried out on the search engines MEDLINE, EMBASE and Web of Science; the quality of the studies included in the review was assessed using the AMSTAR 2 checklist for systematic reviews and the NewCastle-Ottawa Scale for observational studies in the case of cohort and case-control studies and a modified version thereof for ecological and cross-sectional studies. The update was based on the selection of 14 systematic reviews, 15 primary studies, 6 monographs/reports from international scientific organisations on health effects due to the presence of environmental exposure sources.

RESULTS: Mortality. The a priori causes of interest that occur most frequently in excess are, in descending order: malignant lung cancer, malignant mesothelioma of the pleura, malignant bladder cancer, respiratory diseases, non-Hodgkin lymphomas, malignant liver cancer, all malignant tumours, malignant colorectal cancer, malignant stomach cancer, total mesotheliomas, malignant breast cancer, and asbestosis. Hospitalization. The a priori causes of interest that occur most frequently in excess are represented in descending order by: respiratory diseases, malignant lung cancer, malignant tumours of the pleura, malignant bladder cancer, malignant breast cancer, malignant liver cancer, asthma, malignant colorectal cancer, all malignant tumours, malignant stomach cancer, non-Hodgkin's lymphomas, acute respiratory diseases, leukaemias. The differences observed between mortality and hospitalization can be attributed to the intrinsic characteristics of the diseases (higher or lower lethality, gender differences in incidence), lifestyles, and occupational phenomena. Age classes. Excesses of general mortality were observed in the first year of life at the Manfredonia, Basso Bacino Fiume Chienti, Litorale Domizio Flegreo and Agro Aversano sites; in the 0-1 year and 0-19 year age groups at Casale Monferrato; in the paediatric age group at Serravalle Scrivia and at the Trento Nord site; in the 0-19 year age group at Sassuolo Scandiano; in the young age group (0-29 years) at the two municipalities of Cerchiara and Cassano (Crotone-Cassano-Cerchiara site). With regard to hospitalization due to natural causes, risk excesses in both genders are found in the first year of life in 35% of the sites (Porto Torres industrial areas, Bari-Fibronit, Basso bacino fiume Chienti, Bolzano, Crotone-Cassano-Cerchiara, Cerro al Lambro, Bologna ETR large repair workshop, Gela, Manfredonia, Massa Carrara, Pioltello Rodano, Pitelli, Priolo, Sesto San Giovanni, Trento Nord, and Trieste). These same sites, with the addition of Casale Monferrato, Cengio e Saliceto, Serravalle Scrivia, and Sulcis-Iglesiente-Guspinese (total: 43% of sites), show excesses for all natural causes, in both genders, even in the paediatric-adolescent age group (0-19 years). Among young adults (20-29 years), the analyses show excesses of hospitalization for all natural causes in both genders in the Bolzano, Crotone-Cassano-Cerchiara, Gela, Manfredonia, Pitelli, Priolo, and Sulcis-Iglesiente-Guspinese sites. Among young women only, excesses for all natural causes are also found in Brescia Caffaro, Brindisi, Broni, Casale Monferrato, Crotone-Cassano-Cerchiara, Falconara Marittima, Fidenza, and Massa Carrara. Congenital anomalies. In the 21 sites investigated for CA, 10,126 cases of CA, validated by participating registers, were analysed out of 304,620 resident births. Genital CA is the subgroup for which the greatest number of excesses was observed (in 6 out of 21 sites). The available evidence does not allow a causal link to be established between the excesses observed for specific subgroups of ACs and exposure to industrial sources, but the results suggest further action. The interpretation of the results appears, in fact, particularly complex as the scientific literature on the association between exposure to industrial sources and AC is very limited. Socioeconomic status. The sites in which the indicators converge to show the presence of fragility are: Litorale Vesuviano area, Val Basento industrial areas, Basso Bacino fiume Chienti, Biancavilla, Crotone-Cassano-Cerchiara, Litorale Domizio Flegreo and Agro Aversano, Livorno, Massa Carrara, Trieste. Global impact. Over the period 2013-2017, an estimated 8,342 excess deaths (CI90% 1,875-14,809) or approximately 1,668 excess cases/year, 4,353 excess deaths among males (CI90% 334-8,372) and 3,989 among females (CI90% -1,122;9,101). The pooled excess risk of general mortality is 2% in both genders (pooled SMR 1.02; CI90% 1.00-1.04). The proportion of excess deaths to total observed deaths is almost constant over time, rising from 2.5% in 1995-2002 to 2.6% in 2013-2017. The number of deaths in absolute value is also very similar between the periods analysed. Deaths from all malignant tumours contribute the most by accounting for 56% of the observed excesses, the excess risk of mortality from malignant tumours across all sites, compared to the reference populations, is 4% in the male population (pooled SMR 1.04; CI90% 1.01-1.06) and 3% among the female population (pooled SMR 1.03; CI90% 1.01-1.05). Hospitalization (2014-2018) in the 46 sites as a whole was in excess of 3% for all causes, in both genders, for all major disease groups (males: SHR pooled 1.03; CI90% 1.01-1.04 - females: SHR pooled 1.03; CI90% 1.01-1.05). The results for the pooled estimates at the 46 sites on the general population, both with regard to mortality and hospitalization, are consistent in indicating excess risk in both genders for all the diseases considered and, in particular, for all malignancies. A total of 1,409 paediatric-adolescent deaths and 999 young adult deaths were observed, and the pooled analysis of mortality across the 46 sites showed no critical issues, with pooled estimates for all causes, perinatal morbid conditions and all malignancies falling short of expectations. The analysis of hospitalizations, on the other hand, showed an excess risk of 8% (males: SHR pooled 1.08; CI90% 1.03-1.13 - females: SHR pooled 1.08; CI90% 1.03-1.14) for all causes in the first year of life, and in paediatric-adolescent and juvenile age of 3-4% among males (age 0-19 years: SHR pooled 1.04; CI90% 1.02-1.06 - age 20-29 years: SHR pooled 1.03; CI90% 1.00-1.05) and 5% among females (in both age groups; SHR pooled 1.05; CI90% 1.02-1.08). The pooled analysis of mortality for the a priori identified diseases reported excesses for specific diseases in the group of sites with sources of exposure associated with them. Mortality from total mesotheliomas is three times higher at sites with asbestos present (males: pooled SMR 3.02; CI90% 2.18-3.87 - females: pooled SMR 3.61; CI90% 2.33-4.88) and that from pleural mesotheliomas more than two times higher at the group of sites with asbestos and port areas (males: pooled SMR 2.47; CI90% 1.94-3.00 - females: pooled SMR 2.43; CI90% 1.67-3.19). Lung cancer was in excess by 6% among males (pooled SMR 1.06; CI90% 1.03-1.10) and 7% among females (pooled SMR 1.07; CI90% 1.00-1.13). In addition, there are excess mortalities for colorectal cancer at sites with chemical plants, by 4 % among males (SMR pooled 1.04; CI90% 1.01-1.08) and 3 % among females (SMR pooled 1.03; CI90% 1.00-1.07) and for bladder cancer among the male population of sites with landfills (+6 %: SMR pooled 1.06; CI90% 1.02-1.11). Among the diseases of a priori interest, stomach and soft tissue cancers are at fault as a cause of death among all the sites considered.

LITERATURE REVIEW: The update of the epidemiological evidence underlying the Sixth SENTIERI Report has highlighted in the general population a possible association, previously undiscovered, between certain diseases and residence near petrochemical and steel plants, landfills, coal mines and asbestos sources.

CONCLUSIONS AND PERSPECTIVES: Despite the fact that this is an ecological study, and the excesses of pathologies with multifactorial aetiology can never be mechanically attributed solely to the environmental pressure factors that exist or existed in the areas studied, the ability to identify the excesses found in the contaminated sites investigated by the SENTIERI Project confirms the validity of this method of assessing the site-specific health profile, based on the use of epidemiological evidence to identify pathologies of interest a priori. In interpreting the data and lending robustness to what has been observed, comparison with the results obtained in previous Reports is essential. The global estimates give an overall picture that shows excess mortality and hospitalization in these populations compared to the rest of the population, and show how, for specific pathologies, comparable effects are produced at sites with similar contamination characteristics. The themes developed in the in-depth chapters broaden the vision and understanding of the complex interactions between environment and health, describe the possibilities offered by new ways of communicating the results, and confirm the modernity of a Project that began way back in 2006, and that could be grafted onto the objectives of the National Recovery and Resilience Plan within the framework of the Operational Programme Health, Environment, Biodiversity and Climate.}, } @article {pmid36819965, year = {2023}, author = {Gariazzo, C and Gasparrini, A and Marinaccio, A}, title = {Asbestos Consumption and Malignant Mesothelioma Mortality Trends in the Major User Countries.}, journal = {Annals of global health}, volume = {89}, number = {1}, pages = {11}, pmid = {36819965}, issn = {2214-9996}, mesh = {Male ; Humans ; *Mesothelioma, Malignant ; *Asbestos ; *Mesothelioma/epidemiology ; World Health Organization ; Linear Models ; *Lung Neoplasms ; *Pleural Neoplasms ; *Occupational Exposure ; }, abstract = {BACKGROUND: The causal association between mesothelioma and asbestos exposure is conclusive, and many studies have proved that the trend in asbestos use is a strong predictor of the pattern in mesothelioma cases with an adequate latency time (generally around 30-40 years or more). Recently, a novel approach for predicting malignant pleural mesothelioma, based on asbestos consumption trend and using distributed non-linear models, has been applied.

OBJECTIVES: The purpose of this study is to analyse trends in asbestos consumption and malignant mesothelioma mortality in the major asbestos-user countries. Furthermore, we applied distributed non-linear models to estimate and compare epidemiological relationships between asbestos consumption and mesothelioma mortality across these countries.

METHODS: The study involves major asbestos-user countries in which historical asbestos consumption and mesothelioma mortality data are available. Data on asbestos consumption were derived from worldwide asbestos supply and mesothelioma mortality data from World Health Organization (WHO) mortality archives. A quasi-Poisson generalized linear model was used to model past asbestos exposure and male mesothelioma mortality rates in each country. Exposure-response associations have been modelled using distributed lag non-linear models.

FINDINGS AND CONCLUSIONS: According to the criteria defined above, we selected 18 countries with raw asbestos cumulative consumptions higher than two million tons in the period 1933-2012. Overall, a clear linear relationship can be observed between total consumption and total deaths for mesothelioma. Country-specific exposure, lag and age-response relationships were identified and common functions extracted by a meta-analysis procedure. Non-linear models appear suitable and flexible tools for investigating the association between mesothelioma mortality and asbestos consumption. There is a need to improve the global epidemiological surveillance of asbestos-related diseases, particularly mesothelioma mortality, and the absence of reliable data for some major asbestos-user countries is a real concern. A reliable assessment of mesothelioma mortality is a fundamental step towards increasing the awareness of related risks and the need of an international ban on asbestos.}, } @article {pmid36808895, year = {2023}, author = {Sejben, A and Pancsa, T and Tiszlavicz, L and Furák, J and Paróczai, D and Zombori, T}, title = {Highlighting the immunohistochemical differences of malignant mesothelioma subtypes via case presentations.}, journal = {Thoracic cancer}, volume = {14}, number = {10}, pages = {857-863}, pmid = {36808895}, issn = {1759-7714}, mesh = {Humans ; *Mesothelioma, Malignant/diagnosis ; *Mesothelioma/pathology ; Mesothelin ; Calbindin 2 ; Biomarkers, Tumor/metabolism ; Immunohistochemistry ; Diagnosis, Differential ; *Lung Neoplasms/pathology ; }, abstract = {Malignant mesothelioma (MM) is a rare tumor of mesothelial cells, with an increasing incidence both in developed and developing countries. MM has three major histological subtypes, in order of frequency, according to the World Health Organization (WHO) Classification of 2021: epithelioid, biphasic, and sarcomatoid MM. Distinction may be a challenging task for the pathologist, due to the unspecific morphology. Here, we present two cases of diffuse MM subtypes to emphasize the immunohistochemical (IHC) differences, and to facilitate diagnostic difficulties. In our first case of epithelioid mesothelioma, the neoplastic cells showed cytokeratin 5/6 (CK5/6), calretinin, and Wilms-tumor-1 (WT1) expression, while remaining negative with thyroid transcription factor-1 (TTF-1). BRCA1 associated protein-1 (BAP1) negativity was seen in the neoplastic cells' nucleus, reflecting loss of the tumor suppressor gene. In the second case of biphasic mesothelioma, expression of epithelial membrane antigen (EMA), CKAE1/AE3, and mesothelin was observed, while WT1, BerEP4, CD141, TTF1, p63, CD31, calretinin, and BAP1 expressions were not detected. Due to the absence of specific histological features, the differentiation between MM subtypes could be a challenging task. In routine diagnostic work, IHC may be the proper method in distinction. According to our results and literature data, CK5/6, mesothelin, calretinin, and Ki-67 should be applied in subclassification.}, } @article {pmid36800547, year = {2023}, author = {Hocking, AJ and Thomas, EM and Prabhakaran, S and Jolley, A and Woods, SL and Soeberg, MJ and Klebe, S}, title = {Molecular Characterization of Testicular Mesothelioma and the Role of Asbestos as a Causative Factor.}, journal = {Archives of pathology & laboratory medicine}, volume = {147}, number = {12}, pages = {1446-1450}, doi = {10.5858/arpa.2022-0283-OA}, pmid = {36800547}, issn = {1543-2165}, mesh = {Male ; Humans ; *Mesothelioma, Malignant ; *Asbestos/adverse effects ; *Mesothelioma/genetics ; *Testicular Neoplasms/genetics/pathology ; }, abstract = {CONTEXT.—: Mesothelioma of the tunica vaginalis testis (TVT) is an extremely rare form of mesothelioma.

OBJECTIVE.—: To compare the clinical and molecular characteristics of mesothelioma of the TVT with those of mesothelioma at other more common sites, including the relationship with exposure to asbestos.

DESIGN.—: We present clinical and pathological data for 9 cases of primary TVT mesothelioma. We performed whole-genome sequencing on 3 cases for the first time.

RESULTS.—: The majority (7 of 9 cases) of TVT mesotheliomas were epithelioid, with the remaining 2 cases showing biphasic morphology. Morphology and immunohistochemical profiles were indistinguishable from mesothelioma elsewhere. Asbestos exposure was documented for 7 of the 9 cases, with no information for 2 cases. The 3 TVT mesothelioma cases that underwent whole-genome sequencing displayed a mutational profile similar to that of mesothelioma at other sites, including NF2 and TP53 mutations.

CONCLUSIONS.—: The clinical and molecular profile of TVT mesothelioma is similar to that of mesothelioma elsewhere.}, } @article {pmid36785667, year = {2023}, author = {Kapila, D and Panwar, S and Raja, MKMM and Mondal, T and Rafi, SM and Singh, SP and Kumar, B}, title = {Applications of Neural Network-Based Plan-Cancer Method for Primary Diagnosis of Mesothelioma Cancer.}, journal = {BioMed research international}, volume = {2023}, number = {}, pages = {3164166}, pmid = {36785667}, issn = {2314-6141}, mesh = {Humans ; *Mesothelioma, Malignant ; *Mesothelioma/diagnosis/pathology ; Artificial Intelligence ; *Asbestos/toxicity ; Neural Networks, Computer ; }, abstract = {"Malignant mesothelioma (MM)" is an uncommon although fatal form of cancer. The proper MM diagnosis is crucial for efficient therapy and has significant medicolegal implications. Asbestos is a carcinogenic material that poses a health risk to humans. One of the most severe types of cancer induced by asbestos is "malignant mesothelioma." Prolonged shortness of breath and continuous pain are the most typical symptoms of the condition. The importance of early treatment and diagnosis cannot be overstated. The combination "epithelial/mesenchymal appearance of MM," however, makes a definite diagnosis difficult. This study is aimed at developing a deep learning system for medical diagnosis MM automatically. Otherwise, the sickness might cause patients to succumb to death in a short amount of time. Various forms of artificial intelligence algorithms for successful "Malignant Mesothelioma illness" identification are explored in this research. In relation to the concept of traditional machine learning, the techniques support "Vector Machine, Neural Network, and Decision Tree" are chosen. SPSS has been used to analyze the result regarding the applications of Neural Network helps to diagnose MM.}, } @article {pmid36781903, year = {2023}, author = {Vasuri, F and Deserti, M and Corradini, AG and Tavolari, S and Relli, V and Palloni, A and Frega, G and Curti, S and Mattioli, S and Cescon, M and D'Errico, A and Brandi, G}, title = {Asbestos exposure as an additional risk factor for small duct intrahepatic cholangiocarcinoma: a pilot study.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {2580}, pmid = {36781903}, issn = {2045-2322}, mesh = {Humans ; Pilot Projects ; *Asbestos/toxicity ; *Cholangiocarcinoma/etiology/chemically induced ; Risk Factors ; Bile Ducts, Intrahepatic/pathology ; *Bile Duct Neoplasms/etiology/chemically induced ; }, abstract = {Intrahepatic cholangiocarcinoma (iCCA) is a rare malignancy, recently classified in small duct and large duct morphological subtypes. Growing evidence suggests asbestos as a putative risk factor for iCCA, albeit no correlation between asbestos and iCCA morphology has been investigated so far. The aim of the present study was to assess the relationship between asbestos exposure and iCCA morphological subtype. Forty patients with surgically removed iCCA were prospectively enrolled: asbestos exposure was assessed according to the Italian National Mesothelioma Register questionnaire. From the surgical iCCA specimens the main histopathological variables were collected, including the small duct (sd-iCCA, 32 patients) and large duct subtypes (ld-iCCA, 8 patients). Five sd-iCCA cases had a definite/probable occupational exposure to asbestos, while no cases of ld-iCCA were classified as being occupationally exposed (definite/probable). Other kind of asbestos exposure (i.e. possible occupational, familial, environmental) were recorded in 16 sd-iCCA and 3 ld-iCCA. Cases with unlikely exposure to asbestos were 11 sd-iCCA (35.5%) and 5 ld-iCCA (62.5%). In conclusion, these findings seem to indicate that sd-iCCA might be more frequently associated to asbestos exposure rather than ld-iCCA, suggesting that asbestos fibres might represent a parenchymal, rather than a ductal risk factor for iCCA. This pilot study must be confirmed by further case-control studies or large independent cohorts.}, } @article {pmid36781827, year = {2023}, author = {Iwadare, T and Kimura, T and Nagata, Y and Suzuki, H and Kunimoto, H and Kitabatake, H and Seki, A and Ochi, Y and Hara, E and Umemura, T}, title = {A case of malignant peritoneal mesothelioma with a Fitz-Hugh-Curtis syndrome-like imaging finding.}, journal = {Clinical journal of gastroenterology}, volume = {16}, number = {3}, pages = {372-376}, pmid = {36781827}, issn = {1865-7265}, mesh = {Male ; Female ; Humans ; Middle Aged ; *Pelvic Inflammatory Disease/diagnosis ; *Hepatitis/diagnosis ; *Peritonitis/diagnosis ; *Peritoneal Neoplasms/diagnostic imaging/drug therapy ; *Mesothelioma, Malignant ; *Mesothelioma/diagnosis/diagnostic imaging ; }, abstract = {Malignant peritoneal mesothelioma (MPeM) is a rare disease with a poor prognosis that develops in the mesothelial cells of the peritoneum. We encountered a 48-year-old man with no prior asbestos exposure who visited our hospital with abdominal pain. Laboratory findings showed elevated C-reactive protein of 15.5 mg/dL. Contrast-enhanced computed tomography (CT) detected a Fitz-Hugh-Curtis syndrome-like contrast effect on the liver surface and thickening of the peritoneum. Blood culture, Mycobacterium tuberculosis-specific IFN-γ release assay, Chlamydia trachomatis and Neisseria gonorrhoeae DNA testing, and antinuclear antibody were all negative. CA125 was high at 124.8 U/mL. The laparoscopy for diagnostic purposes revealed adhesions between the liver surface and peritoneum in addition to numerous small and large white nodules on the peritoneum. Biopsy of the nodules confirmed the diagnosis of epithelial-type MPeM. Treatment was initiated with combined cisplatin and pemetrexed, and CT 6 months later showed a reduced contrast effect on the liver surface and improved peritoneal thickening. A Fitz-Hugh-Curtis syndrome-like contrast effect on the liver surface on contrast-enhanced CT may help identify MPeM.}, } @article {pmid36775192, year = {2023}, author = {Huang, J and Chan, SC and Pang, WS and Chow, SH and Lok, V and Zhang, L and Lin, X and Lucero-Prisno, DE and Xu, W and Zheng, ZJ and Elcarte, E and Withers, M and Wong, MCS and , }, title = {Global Incidence, Risk Factors, and Temporal Trends of Mesothelioma: A Population-Based Study.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {18}, number = {6}, pages = {792-802}, doi = {10.1016/j.jtho.2023.01.095}, pmid = {36775192}, issn = {1556-1380}, mesh = {Female ; Humans ; Male ; Incidence ; *Lung Neoplasms/complications ; *Mesothelioma/epidemiology/etiology ; *Mesothelioma, Malignant ; *Asbestos/adverse effects ; Risk Factors ; }, abstract = {INTRODUCTION: Mesothelioma is an uncommon type of cancer which has received little attention. This study aims to evaluate the global disease burden; trends of mesothelioma by age, sex, and geographic locations; and its risk factors on the population level.

METHODS: The Global Cancer Observatory, Cancer Incidence in Five Continents Plus, and Global Burden of Disease were accessed for mesothelioma incidence and its risk factors worldwide. The associations between mesothelioma incidence and asbestos were evaluated for each country by multivariable linear regression analysis by sex and age. Average annual percentage change (AAPC) was calculated using Joinpoint regression to evaluate the epidemiologic trends of mesothelioma.

RESULTS: The age-standardized rate of mesothelioma was 0.30 per 100,000 persons with Northern Europe reporting the highest incidence rates. The incidence rate of the male population was much higher than that of the females. Countries with higher human development index (β = 0.119, confidence interval [CI]: 0.073-0.166, p < 0.001), gross domestic product per capita (β = 0.133, CI: 0.106-0.161, p < 0.001), and asbestos exposure (β = 0.087, CI: 0.073-0.102, p < 0.001) had higher mesothelioma. The overall trend of mesothelioma incidence was decreasing, although an increase was observed in Bulgaria (AAPC: 5.56, 95% CI: 2.94-8.24, p = 0.001) and Korea (AAPC: 3.24, 95% CI: 0.08-6.49, p = 0.045).

CONCLUSIONS: There was a substantial declining incidence trend of mesothelioma in the past decade possibly related to the restriction of the use of asbestos in some countries. Meanwhile, the increasing trend in mesothelioma incidence observed in females might be indicative of an increase in environmental exposure to mineral fibers.}, } @article {pmid36765599, year = {2023}, author = {Palstrøm, NB and Overgaard, M and Licht, P and Beck, HC}, title = {Identification of Highly Sensitive Pleural Effusion Protein Biomarkers for Malignant Pleural Mesothelioma by Affinity-Based Quantitative Proteomics.}, journal = {Cancers}, volume = {15}, number = {3}, pages = {}, pmid = {36765599}, issn = {2072-6694}, support = {NA//Odense University Hospital/ ; }, abstract = {Malignant pleural mesothelioma (MPM) is an asbestos-associated, highly aggressive cancer characterized by late-stage diagnosis and poor prognosis. Gold standards for diagnosis are pleural biopsy and cytology of pleural effusion (PE), both of which are limited by low sensitivity and markedly inter-observer variations. Therefore, the assessment of PE biomarkers is considered a viable and objective diagnostic tool for MPM diagnosis. We applied a novel affinity-enrichment mass spectrometry-based proteomics method for explorative analysis of pleural effusions from a prospective cohort of 84 patients referred for thoracoscopy due to clinical suspicion of MPM. Protein biomarkers with a high capability to discriminate MPM from non-MPM patients were identified, and a Random Forest algorithm was applied for building classification models. Immunohistology of pleural biopsies confirmed MPM in 40 patients and ruled out MPM in 44 patients. Proteomic analysis of pleural effusions identified panels of proteins with excellent diagnostic properties (90-100% sensitivities, 89-98% specificities, and AUC 0.97-0.99) depending on the specific protein combination. Diagnostic proteins associated with cancer growth included galactin-3 binding protein, testican-2, haptoglobin, Beta ig-h3, and protein AMBP. Moreover, we also confirmed previously reported diagnostic accuracies of the MPM markers fibulin-3 and mesothelin measured by two complementary mass spectrometry-based methods. In conclusion, a novel affinity-enrichment mass spectrometry-based proteomics identified panels of proteins in pleural effusion with extraordinary diagnostic accuracies, which are described here for the first time as biomarkers for MPM.}, } @article {pmid36765038, year = {2023}, author = {Yang, H and Gao, Y and Xu, D and Xu, K and Liang, SQ and Yang, Z and Scherz, A and Hall, SRR and Forster, S and Berezowska, S and Yao, F and Ochsenbein, AF and Marti, TM and Kocher, GJ and Schmid, RA and Dorn, P and Peng, RW}, title = {MEK1 drives oncogenic signaling and interacts with PARP1 for genomic and metabolic homeostasis in malignant pleural mesothelioma.}, journal = {Cell death discovery}, volume = {9}, number = {1}, pages = {55}, pmid = {36765038}, issn = {2058-7716}, support = {KFS-4851-08-2019//Krebsliga Schweiz (Ligue Suisse Contre le Cancer)/ ; 310030_192648//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)/ ; }, abstract = {Malignant pleural mesothelioma (MPM) is a lethal malignancy etiologically caused by asbestos exposure, for which there are few effective treatment options. Although asbestos carcinogenesis is associated with reactive oxygen species (ROS), the bona fide oncogenic signaling pathways that regulate ROS homeostasis and bypass ROS-evoked apoptosis in MPM are poorly understood. In this study, we demonstrate that the mitogen-activated protein kinase (MAPK) pathway RAS-RAF-MEK-ERK is hyperactive and a molecular driver of MPM, independent of histological subtypes and genetic heterogeneity. Suppression of MAPK signaling by clinically approved MEK inhibitors (MEKi) elicits PARP1 to protect MPM cells from the cytotoxic effects of MAPK pathway blockage. Mechanistically, MEKi induces impairment of homologous recombination (HR) repair proficiency and mitochondrial metabolic activity, which is counterbalanced by pleiotropic PARP1. Consequently, the combination of MEK with PARP inhibitors enhances apoptotic cell death in vitro and in vivo that occurs through coordinated upregulation of cytotoxic ROS in MPM cells, suggesting a mechanism-based, readily translatable strategy to treat this daunting disease. Collectively, our studies uncover a previously unrecognized scenario that hyperactivation of the MAPK pathway is an essential feature of MPM and provide unprecedented evidence that MAPK signaling cooperates with PARP1 to homeostatically maintain ROS levels and escape ROS-mediated apoptosis.}, } @article {pmid36757881, year = {2023}, author = {Bonde, A and Singh, R and Prasad, SR and Kamireddy, D and Aggarwal, A and Ramani, N and Saboo, S and Shanbhogue, K and Dasyam, AK and Katabathina, VS}, title = {Mesotheliomas and Benign Mesothelial Tumors: Update on Pathologic and Imaging Findings.}, journal = {Radiographics : a review publication of the Radiological Society of North America, Inc}, volume = {43}, number = {3}, pages = {e220128}, doi = {10.1148/rg.220128}, pmid = {36757881}, issn = {1527-1323}, mesh = {Humans ; *Adenomatoid Tumor ; Positron Emission Tomography Computed Tomography ; *Mesothelioma/diagnostic imaging/therapy ; *Mesothelioma, Malignant ; *Pleural Neoplasms/pathology ; *Neoplasms, Mesothelial ; Biomarkers, Tumor ; }, abstract = {A diverse spectrum of benign entities and malignant neoplasms originate from the monotonous mesothelium that lines the serosal membranes of the pleural, pericardial, and peritoneal cavities. The mesothelium of myriad sites shows a common origin from the lateral plate mesoderm; primary mesothelial tumors thus demonstrate similar pathogenesis, imaging findings, and treatment options. Significant changes have been made in the 2021 World Health Organization (WHO) classification schemata of the pleural and pericardial tumors on the basis of recent advances in pathology and genetics. While malignant mesotheliomas are biologically aggressive malignancies that occur primarily in patients exposed to asbestos with attendant poor survival rates, well-differentiated papillary mesothelial tumors and adenomatoid tumors charter a benign clinical course with an excellent prognosis. Mesothelioma in situ is a newly characterized entity represented by recurrent unexplained pleural effusions without any identifiable mass at imaging or thoracoscopy. Immunohistochemical markers based on BAP1, MTAP, CDKN2A, and TRAF7 gene mutations help differentiate diffuse mesotheliomas from benign mesothelial proliferations and localized mesotheliomas. Cross-sectional imaging modalities, including US, CT, MRI, and fluorine 18-fluorodeoxyglucose (FDG) PET/CT, permit diagnosis and play a major role in staging and assessing surgical resectability. Imaging studies are invaluable in providing noninvasive and quantitative assessment of tumor response in patients with unresectable disease. Owing to significant overlap in patient characteristics and pathomorphology, accurate diagnosis based on advanced histopathology techniques and genetic abnormalities is imperative for optimal management and prognostication. While patients with nonepithelioid pleural mesotheliomas benefit from immunotherapy, novel targeted therapies for CDKN2A-, NF2-, and BAP1-altered mesotheliomas are under consideration. [©] RSNA, 2023 Quiz questions for this article are available through the Online Learning Center.}, } @article {pmid36754595, year = {2023}, author = {Walker-Bone, K and Benke, G and MacFarlane, E and Klebe, S and Takahashi, K and Brims, F and Sim, MR and Driscoll, TR}, title = {Incidence and mortality from malignant mesothelioma 1982-2020 and relationship with asbestos exposure: the Australian Mesothelioma Registry.}, journal = {Occupational and environmental medicine}, volume = {80}, number = {4}, pages = {186-191}, doi = {10.1136/oemed-2022-108669}, pmid = {36754595}, issn = {1470-7926}, mesh = {Male ; Humans ; Female ; Aged, 80 and over ; *Mesothelioma, Malignant/chemically induced/complications ; Incidence ; Australia/epidemiology ; *Mesothelioma/etiology ; *Asbestos/adverse effects ; *Occupational Exposure/adverse effects ; Registries ; }, abstract = {OBJECTIVES: Malignant mesothelioma is an uncommon cancer associated with asbestos exposure, predominantly occupational. Asbestos has been banned in Australia since 2003 but mesothelioma has a long latency and incident cases continue to present. The Australian Mesothelioma Registry was incepted to collect systematic data about incidence and mortality alongside asbestos exposure.

METHODS: Benefiting from the Australian national system of cancer notification, all incident cases of mesothelioma in all states and territories are fast-tracked and notified regularly. Notified patients are contacted asking for consent to collect exposure information, initially by postal questionnaire and subsequently by telephone interview. Age-standardised annual incidence rates and mortality rates were calculated. Asbestos exposure was categorised as occupational, non-occupational, neither or, both; and as low, or high, probability of exposure.

RESULTS: Mesothelioma incidence appears to have peaked. The age-standardised incidence rates have declined steadily since the early 2000s (peaking in males at 5.9/100 000 and in all-persons at 3.2/100 000), driven by rates in males, who comprise the majority of diagnosed cases. Rates in women have remained fairly stable since that time. Age-standardised mortality rates have followed similar trends. Mesothelioma remains the most common in those aged over 80 years. Nearly all (94%) cases were linked with asbestos exposure (78% occupational in men; 6.8% in women).

CONCLUSIONS: With effective control of occupational asbestos use, the decline in age-standardised incidence and death rates has occurred. Incidence rates among women, in whom occupational asbestos exposure is rarely detectable, remain unchanged, pointing to the role of household and /or environmental asbestos exposure.}, } @article {pmid36740402, year = {2023}, author = {Cunningham, R and Jia, S and Purohit, K and Salem, O and Hui, NS and Lin, Y and Carragher, NO and Hansen, CG}, title = {YAP/TAZ activation predicts clinical outcomes in mesothelioma and is conserved in in vitro model of driver mutations.}, journal = {Clinical and translational medicine}, volume = {13}, number = {2}, pages = {e1190}, pmid = {36740402}, issn = {2001-1326}, support = {19-0238/AICR_/Worldwide Cancer Research/United Kingdom ; 204804/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; Hippo Signaling Pathway ; *Mesothelioma/genetics/metabolism/pathology ; Mutation/genetics ; Protein Serine-Threonine Kinases/metabolism ; *Transcription Factors/genetics/metabolism ; Transcriptional Coactivator with PDZ-Binding Motif Proteins ; YAP-Signaling Proteins ; }, abstract = {The Hippo signalling pathway is dysregulated across a wide range of cancer types and, although driver mutations that directly affect the core Hippo components are rare, a handful is found within pleural mesothelioma (PM). PM is a deadly disease of the lining of the lung caused by asbestos exposure. By pooling the largest-scale clinical datasets publicly available, we here interrogate associations between the most prevalent driver mutations within PM and Hippo pathway disruption in patients, while assessing correlations with a variety of clinical markers. This analysis reveals a consistent worse outcome in patients exhibiting transcriptional markers of YAP/TAZ activation, pointing to the potential of leveraging Hippo pathway transcriptional activation status as a metric by which patients may be meaningfully stratified. Preclinical models recapitulating disease are transformative in order to develop new therapeutic strategies. We here establish an isogenic cell-line model of PM, which represents the most frequently mutated genes and which faithfully recapitulates the molecular features of clinical PM. This preclinical model is developed to probe the molecular basis by which the Hippo pathway and key driver mutations affect cancer initiation and progression. Implementing this approach, we reveal the role of NF2 as a mechanosensory component of the Hippo pathway in mesothelial cells. Cellular NF2 loss upon physiological stiffnesses analogous to the tumour niche drive YAP/TAZ-dependent anchorage-independent growth. Consequently, the development and characterisation of this cellular model provide a unique resource to obtain molecular insights into the disease and progress new drug discovery programs together with future stratification of PM patients.}, } @article {pmid36729166, year = {2023}, author = {Slavik, CE and Demers, PA and Tamburic, L and Warden, H and McLeod, C}, title = {Do patterns of past asbestos use and production reflect current geographic variations of cancer risk?: mesothelioma in Ontario and British Columbia, Canada.}, journal = {Cancer causes & control : CCC}, volume = {34}, number = {4}, pages = {349-360}, pmid = {36729166}, issn = {1573-7225}, support = {RS2018-SP27//WorkSafeBC/ ; }, mesh = {Humans ; British Columbia/epidemiology ; Ontario/epidemiology ; *Mesothelioma/epidemiology/etiology ; *Asbestos/adverse effects ; Environmental Exposure ; Incidence ; *Occupational Exposure/adverse effects ; }, abstract = {PURPOSE: Canada was a major global asbestos producer and consumer. Geographic patterns of Canadian asbestos use and mesothelioma, a highly fatal cancer linked to asbestos exposure, have not been previously reported. This study summarized key trends in mesothelioma incidence by geography and time in two Canadian provinces, Ontario and British Columbia (BC), and explored how past workforce characteristics and geographic trends in asbestos production and use may shape variations in regional rates of mesothelioma.

METHODS: We report trends in mesothelioma incidence (1993-2016) for Ontario and British Columbia using population-based incidence data that were age-standardized to the 2011 Canadian population. Historical records of asbestos production and use were analyzed to geo-locate industrial point sources of asbestos in Ontario and BC. The prevalence of occupations in regions with the highest and lowest rates of mesothelioma in Ontario and BC were calculated using labor force statistics from the 1981 Canadian Census.

RESULTS: Regional mesothelioma rates varied in both provinces over time; more census divisions in both Ontario and BC registered mesothelioma rates in the highest quintile of incidences during the period 2009 to 2016 than in any prior period examined. Certain occupations such as construction trades workers were more likely to be overrepresented in regions with high mesothelioma rates.

CONCLUSION: This work explored how studying asbestos exposure and mesothelioma incidence at small-scale geographies could direct cancer surveillance and research to more targeted areas. Findings indicated that regional variations in mesothelioma could signal important differences in past occupational and potentially environmental exposures.}, } @article {pmid36724751, year = {2023}, author = {Endo, I and Amatya, VJ and Kushitani, K and Nakagiri, T and Aoe, K and Takeshima, Y}, title = {miR-142-3p Suppresses Invasion and Adhesion of Mesothelioma Cells by Downregulating ITGAV.}, journal = {Pathobiology : journal of immunopathology, molecular and cellular biology}, volume = {90}, number = {4}, pages = {270-280}, doi = {10.1159/000528670}, pmid = {36724751}, issn = {1423-0291}, mesh = {Humans ; *Mesothelioma, Malignant/genetics ; Cell Movement/genetics ; Cell Line, Tumor ; *Mesothelioma/genetics ; *MicroRNAs/genetics/metabolism ; RNA, Small Interfering/metabolism ; Cell Proliferation/genetics ; Gene Expression Regulation, Neoplastic ; }, abstract = {INTRODUCTION: Malignant mesothelioma is an aggressive cancer associated with asbestos exposure. Currently, the efficacy of therapeutics is limited in malignant mesothelioma, and developing more effective therapies is the need of the hour. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), have attracted attention as therapeutic targets. To explore potential therapeutic targets, we focused on miR-142-3p expression, which was found to be significantly downregulated in mesothelioma cell lines in our previous study.

METHODS: Mesothelioma cell lines and tissues were validated for expression of miR-142-3p or integrin subunit alpha-V (ITGAV). We transfected mesothelioma cell lines with miR-142-3p mimic and ITGAV siRNA and analyzed their biological functions.

RESULTS: We found that miR-142-3p was significantly downregulated in mesothelioma tissues. Transfection with miR-142-3p mimic significantly suppressed cell proliferation, migration, and invasion. Bioinformatics analysis of potential targets of miR-142-3p identified ITGAV. Membrane ITGAV expression in mesothelioma cell lines was confirmed using immunocytochemistry. ITGAV was significantly upregulated in mesothelioma tissues. Moreover, transfection of miR-142-3p mimics into mesothelioma cell lines significantly suppressed ITGAV expression, indicating that miR-142-3p targets ITGAV. Next, ITGAV siRNA transfection into mesothelioma cell lines inhibited cell proliferation, migration, and invasion. Further investigation of cell adhesion mechanisms showed that the miR-142-3p/ITGAV axis specifically affects mesothelioma cell adhesion via vitronectin in the extracellular matrix.

CONCLUSION: This study proposed that the miR-142-3p/ITGAV axis is involved in tumor progression in malignant mesothelioma.}, } @article {pmid36720634, year = {2023}, author = {Del Monaco, A and Dimitriadis, C and Xie, S and Benke, G and Sim, MR and Walker-Bone, K}, title = {Workers in Australian prebake aluminium smelters: update on risk of mortality and cancer incidence in the Healthwise cohort.}, journal = {Occupational and environmental medicine}, volume = {80}, number = {3}, pages = {160-169}, doi = {10.1136/oemed-2022-108605}, pmid = {36720634}, issn = {1470-7926}, mesh = {Humans ; Male ; Aluminum/adverse effects ; Incidence ; Cohort Studies ; *Occupational Diseases/etiology ; Australia/epidemiology ; *Neoplasms ; *Mesothelioma/etiology ; *Lung Neoplasms ; Cause of Death ; *Mesothelioma, Malignant/complications ; *Occupational Exposure/adverse effects ; }, abstract = {OBJECTIVES: To investigate mortality and the rates of incident cancer among a cohort of aluminium industry workers.

METHODS: Among 4507 male employees who worked in either of two Australian prebake smelters for at least 3 months, data linkage was undertaken with the Australian National Death Index and Australian Cancer Database. Standardised Mortality Ratios (SMRs) and Standardised Incidence Rates (SIRs) were estimated for the whole cohort and for: production; maintenance and office workers. SMRs and SIRs were calculated by time since first employment.

RESULTS: Among production workers, there was an excess risk of mortality from mesothelioma (SMR 2.8, 95% CI 1.3 to 5.2), lung (SMR 1.4, 95% CI 1.0 to 1.8), prostate (SMR 1.9, 95% CI 1.3 to 2.7) and liver cancer (SMR 2.0, 95% CI 1.1 to 3.4) and the SIR was also increased for overall respiratory cancers, specifically lung cancers. An excess risk of death from stomach cancer (SMR 2.9, 95% CI 1.2 to 6.1) and Alzheimer's disease (SMR 3.4, 95% CI 1.1 to 7.9) was seen among maintenance workers. The overall risk of death was similar to that of the Australian general population, as was mortality from cancers overall and non-malignant respiratory disease.

CONCLUSIONS: No excess risk of death from bladder cancer or non-malignant respiratory disease was found. Excess lung cancer mortality and incidence may be explained by smoking and excess mortality from mesothelioma may be explained by asbestos exposure. An excess risk of mortality from liver and prostate cancer has been shown in production workers and requires further investigation.}, } @article {pmid36705549, year = {2022}, author = {Di Genova, A and Mangiante, L and Sexton-Oates, A and Voegele, C and Fernandez-Cuesta, L and Alcala, N and Foll, M}, title = {A molecular phenotypic map of malignant pleural mesothelioma.}, journal = {GigaScience}, volume = {12}, number = {}, pages = {}, pmid = {36705549}, issn = {2047-217X}, support = {001/WHO_/World Health Organization/International ; }, mesh = {Humans ; *Mesothelioma, Malignant ; *Mesothelioma/genetics/pathology ; *Lung Neoplasms/genetics/pathology ; *Pleural Neoplasms/genetics/pathology ; Phenotype ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare understudied cancer associated with exposure to asbestos. So far, MPM patients have benefited marginally from the genomics medicine revolution due to the limited size or breadth of existing molecular studies. In the context of the MESOMICS project, we have performed the most comprehensive molecular characterization of MPM to date, with the underlying dataset made of the largest whole-genome sequencing series yet reported, together with transcriptome sequencing and methylation arrays for 120 MPM patients.

RESULTS: We first provide comprehensive quality controls for all samples, of both raw and processed data. Due to the difficulty in collecting specimens from such rare tumors, a part of the cohort does not include matched normal material. We provide a detailed analysis of data processing of these tumor-only samples, showing that all somatic alteration calls match very stringent criteria of precision and recall. Finally, integrating our data with previously published multiomic MPM datasets (n = 374 in total), we provide an extensive molecular phenotype map of MPM based on the multitask theory. The generated map can be interactively explored and interrogated on the UCSC TumorMap portal (https://tumormap.ucsc.edu/?p=RCG_MESOMICS/MPM_Archetypes).

CONCLUSIONS: This new high-quality MPM multiomics dataset, together with the state-of-art bioinformatics and interactive visualization tools we provide, will support the development of precision medicine in MPM that is particularly challenging to implement in rare cancers due to limited molecular studies.}, } @article {pmid36687288, year = {2023}, author = {Romano, M and Pinto, P and Afonso, R and Fontes, J and Ferreira, M}, title = {Pleural Mesothelioma: A Rapid Evolution of an Indolent Disease.}, journal = {Cureus}, volume = {15}, number = {1}, pages = {e33965}, pmid = {36687288}, issn = {2168-8184}, abstract = {Mesothelioma is a rare and insidious neoplasm and is characterized by its highly malignant and aggressive nature. The most common etiology is asbestos exposure, but there are some reports without known asbestos exposure and other factors leading to malignant pleural mesothelioma (MPM). Here, we present the case of a 58-year-old woman with pleuritic chest pain, dyspnea, and fever on presentation to the emergency department (ED), which caused several admissions to the ED in 20 days. The patient was then admitted to the internal medicine department with a diagnosis of community-acquired pneumonia with parapneumonic effusion. During hospitalization, a positron emission tomography (PET) scan, thoracic computed tomography (CT), and pleural biopsy were performed and a final diagnosis of malignant epithelioid pleural mesothelioma was made. Six weeks after the onset of symptoms, the patient presented with an exponential disease progression, dying two months after the diagnosis, despite the initiation of chemotherapy. MPM remains a diagnostic and therapeutic challenge with a very poor prognosis. However, studies show that mesothelioma patients who undergo treatment live at least twice as long as patients who do not receive treatment. This case report is particularly significant because, although it was epithelioid mesothelioma, multiple solid masses were noted on CT and the patient exhibited rapid disease progression, dying a few weeks after starting treatment.}, } @article {pmid36673690, year = {2023}, author = {Magnani, C and Mensi, C and Binazzi, A and Marsili, D and Grosso, F and Ramos-Bonilla, JP and Ferrante, D and Migliore, E and Mirabelli, D and Terracini, B and Consonni, D and Degiovanni, D and Lia, M and Cely-García, MF and Giraldo, M and Lysaniuk, B and Comba, P and Marinaccio, A}, title = {The Italian Experience in the Development of Mesothelioma Registries: A Pathway for Other Countries to Address the Negative Legacy of Asbestos.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {2}, pages = {}, pmid = {36673690}, issn = {1660-4601}, mesh = {Female ; Humans ; *Lung Neoplasms/epidemiology ; *Asbestos/toxicity ; *Mesothelioma/epidemiology/etiology ; *Mesothelioma, Malignant ; *Carcinogens, Environmental ; Registries ; Italy/epidemiology ; }, abstract = {Asbestos (all forms, including chrysotile, crocidolite, amosite, tremolite, actinolite, and anthophyllite) is carcinogenic to humans and causally associated with mesothelioma and cancer of the lung, larynx, and ovary. It is one of the carcinogens most diffuse in the world, in workplaces, but also in the environment and is responsible for a very high global cancer burden. A large number of countries, mostly with high-income economies, has banned the use of asbestos which, however, is still widespread in low- and middle-income countries. It remains, thus, one of the most common occupational and environmental carcinogens worldwide. Italy issued an asbestos ban in 1992, following the dramatic observation of a large increase in mortality from mesothelioma and other asbestos-related diseases in exposed workers and also in subjects with non-occupational exposure. A mesothelioma registry was also organized and still monitors the occurrence of mesothelioma cases, conducting a case-by-case evaluation of asbestos exposure. In this report, we describe two Italian communities, Casale Monferrato and Broni, that faced an epidemic of mesothelioma resulting from the production of asbestos cement and the diffuse environmental exposure; we present the activity and results of the Italian mesothelioma registry (ReNaM), describe the risk-communication activities at the local and national level with a focus on international cooperation and also describe the interaction between mesothelioma registration and medical services specialized in mesothelioma diagnosis and treatment in an area at high risk of mesothelioma. Finally, we assess the potential application of the solutions and methods already developed in Italy in a city in Colombia with high mesothelioma incidence associated with the production of asbestos-cement materials and the presence of diffuse environmental asbestos pollution.}, } @article {pmid36653798, year = {2023}, author = {Moline, J and Patel, K and Frank, AL}, title = {Exposure to cosmetic talc and mesothelioma.}, journal = {Journal of occupational medicine and toxicology (London, England)}, volume = {18}, number = {1}, pages = {1}, pmid = {36653798}, issn = {1745-6673}, abstract = {AIM: Mesothelioma is associated with asbestos exposure. In this case series, we present 166 cases of individuals who had substantial asbestos exposure to cosmetic talc products as well as some who had potential or documented additional exposures to other asbestos-containing products and who subsequently developed mesothelioma.

METHODS: Data were gathered for all subjects referred to an occupational and environmental medicine specialist as part of medicolegal review. Years of total cosmetic talcum powder usage was noted as well as the latency from the onset of talcum powder use to the mesothelioma diagnosis. Alternate asbestos exposure in addition to the exposure from cosmetic talc was categorized as none, possible, likely, and definite.

RESULTS: In 122 cases, the only known exposure to asbestos was from cosmetic talc. For 44 cases, potential or documented alternate exposures in addition to the cosmetic talc were described.

CONCLUSION: Cumulative exposure to asbestos leads to mesothelioma; for individuals with mixed exposures to asbestos, all exposures should be considered. Use of cosmetic talc is often overlooked as a source of asbestos exposure. All individuals with mesothelioma should have a comprehensive history of asbestos exposure, including cosmetic talc exposure.}, } @article {pmid36646495, year = {2022}, author = {Piao, ZH and Zhou, XC and Zhang, X}, title = {[Updates in the pathological diagnosis of Pleural Malignant Mesothelioma in the WHO classification of thoracic tumors (5(th) edition)].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {40}, number = {12}, pages = {956-960}, doi = {10.3760/cma.j.cn121094-20211105-00546}, pmid = {36646495}, issn = {1001-9391}, support = {2022-F30//China-Japan Project for the Improvement of Diagnosis of Asbestos-related Cancer/ ; //Project of NiNGBO leading Medical & Health Discipline/ ; }, mesh = {Humans ; *Mesothelioma, Malignant ; *Pleural Neoplasms/diagnosis ; *Mesothelioma/diagnosis ; Prognosis ; World Health Organization ; *Lung Neoplasms/diagnosis/pathology ; }, abstract = {The WHO Classification of Thoracic Tumors (5(th) edition) mainly has the following changes in the chapter of pleural malignant mesothelioma. (1) The concept of mesothelioma in situ and its diagnostic method have been established for the first time; (2) The tumour grading of pleural malignant mesothelioma was added, it was divided into low grade and high grade according to the cellular atypia, mitotic activity and presence of necrosis. (3) The morphological features of pleural malignant mesothelioma was classified into architectural pattern, cellular and stromal features, the correlation between histological features and prognosis was refined, and some of the controversial cellular types have been reclassified. In this review, we introduced the changes of related pathologic diagnosis, in the WHO Classification of Thoracic Tumors (5(th) edition) and discussed its clinical significance.}, } @article {pmid36636687, year = {2022}, author = {Neff, D and Padberg Sgier, BC and Dietze, H and Müller, J and Früh, M}, title = {Unusually Aggressive Presentation of Malignant Peritoneal Mesothelioma: Two Case Reports.}, journal = {Case reports in oncology}, volume = {15}, number = {3}, pages = {1001-1008}, pmid = {36636687}, issn = {1662-6575}, abstract = {Malignant peritoneal mesothelioma is a rare disease. Patients mainly present with abdominal distension, pain, nausea, and weight loss with or without an exposure history of asbestos. Diagnosis may be difficult from a clinical and histopathologic perspective. Treatment options are surgery in early stages, radiotherapy and/or intraperitoneal or systemic therapy. Prognosis depends on TNM stage and histologic subtype with epithelioid subtype being the most favorable one but in general remains poor. We present a 59-year-old male (patient 1) and a 79-year-old female (patient 2) with progressive dyspnea. PET-CT of patient 1 revealed metastatic spread in the pleura and extensive peritoneal carcinomatosis. PET-CT of patient 2 displayed FDG-avid lymph nodes on both sides of the diaphragm, polyserositis, and FDG uptake along the peritoneum. Both patients were eventually diagnosed with malignant peritoneal mesothelioma. Patient 1 was treated with carboplatin and gemcitabine, and patient 2 received no systemic therapy. Even though the epithelioid subtype was found, both patients succumbed due to rapid tumor progression in a matter of a few weeks only. Presentation with polyserositis even in the absence of relevant asbestos exposure may represent malignant peritoneal mesothelioma if ascites is present, and rapid invasive diagnostic (excision biopsy) should be performed. These two unusual cases emphasize that even in epithelioid subtype, clinicians ought to be aware of possible rapid clinical deterioration, and timely diagnosis with initiation of therapy is crucial. Further research is necessary to better understand tumor biology, establish predictive markers, and develop new treatment options.}, } @article {pmid36636360, year = {2022}, author = {Dusseault, SK and Okobi, OE and Thakral, N and Sankar, V and Gunawardene, I and Dawkins, B and Abu, Y and Davis, B}, title = {Primary Peritoneal Mesothelioma: Diagnostic Challenges of This Lethal Imposter.}, journal = {Case reports in gastroenterology}, volume = {16}, number = {3}, pages = {588-594}, pmid = {36636360}, issn = {1662-0631}, abstract = {Primary Peritoneal Mesothelioma is a rapidly aggressive and rare neoplasm that arises from the lining of mesothelial cells of the peritoneum and spreads extensively within the confines of the abdominal cavity. The pathogenesis of all forms of mesothelioma is strongly associated with industrial pollutants, of which asbestos is the principal carcinogen. Characteristically, asbestos exposure has a strong relationship with mesothelioma of the pleura, but the peritoneal cavity is the second most commonly affected site. Additionally, in contrast to pleural mesothelioma, which has a male predominance (male-female ratio of between four and five to one), women comprise approximately one-half of all cases of malignant peritoneal mesothelioma. A thorough history of occupational/paraoccupational exposure along with histopathology is the key to timely diagnosis and treatment.}, } @article {pmid36635096, year = {2023}, author = {Kurth, L and Mazurek, JM and Blackley, DJ}, title = {Malignant mesothelioma among US Medicare beneficiaries: incidence, prevalence and therapy, 2016-2019.}, journal = {Occupational and environmental medicine}, volume = {80}, number = {2}, pages = {86-92}, pmid = {36635096}, issn = {1470-7926}, support = {CC999999/ImCDC/Intramural CDC HHS/United States ; }, mesh = {Humans ; Aged ; United States/epidemiology ; *Medicare ; *Mesothelioma, Malignant ; Prevalence ; Incidence ; Fee-for-Service Plans ; }, abstract = {OBJECTIVES: Mesothelioma is a rare, aggressive cancer caused by exposure to asbestos fibres. Mesothelioma patients who receive trimodal therapy (chemotherapy, surgical resection and radiation) survive longer than those who receive two or fewer therapy modalities. This study analyses the 2016-2019 Medicare claims data to estimate the burden of malignant mesothelioma and describe therapy patterns (when available) among continuously enrolled fee-for-service (FFS; Medicare parts A and B) beneficiaries.

METHODS: We analysed claims and enrolment information from 42 529 117 FFS Medicare beneficiaries using three mesothelioma case definitions (broad, intermediate and narrow) with varying levels of diagnostic requirements. Results are presented as ranges of values for the three definitions.

RESULTS: Among FFS beneficiaries, 8213-19 036 beneficiaries with mesothelioma were identified depending on the case definition. The annual prevalence per 100 000 beneficiaries ranged from 8.8 in 2016 (narrow) to 31.3 in 2019 (broad) and annual incidence per 100 000 beneficiaries ranged from 4.5 in 2019 (narrow) to 12.6 in 2017 (broad). Depending on the mesothelioma case definition, 41.8%-81.5% had available therapy claim information indicating that 7.6%-11.3% received chemotherapy alone, 1.3%-1.5% received radiation alone, and 14.3%-27.0% underwent surgery only, with 4.6%-10.5% receiving all three therapy modalities.

CONCLUSIONS: Mesothelioma was a prevalent disease among FFS Medicare beneficiaries during 2016-2019, and a limited proportion of beneficiaries received all three therapy modalities. Medicare data build on findings from cancer registry data to enhance our understanding of the mesothelioma burden and therapy patterns.}, } @article {pmid36630203, year = {2023}, author = {Caceres, JD and Venkata, AN}, title = {Asbestos-associated pulmonary disease.}, journal = {Current opinion in pulmonary medicine}, volume = {29}, number = {2}, pages = {76-82}, pmid = {36630203}, issn = {1531-6971}, mesh = {Humans ; *Mesothelioma/etiology/pathology ; *Asbestos/toxicity ; *Pleural Diseases/diagnostic imaging/etiology ; *Lung Diseases/complications ; *Asbestosis/complications/diagnostic imaging/pathology ; *Pleural Effusion/etiology ; *Lung Neoplasms/chemically induced ; *Mesothelioma, Malignant/complications ; }, abstract = {PURPOSE OF REVIEW: Exposure to asbestos can cause both benign and malignant, pulmonary and pleural diseases. In the current era of low asbestos exposure, it is critical to be aware of complications from asbestos exposure; as they often arise after decades of exposure, asbestos-related pulmonary complications include asbestosis, pleural plaques, diffuse pleural thickening, benign asbestos-related pleural effusions and malignant pleural mesothelioma.

RECENT FINDINGS: Multiple recent studies are featured in this review, including a study evaluating imaging characteristics of asbestos with other fibrotic lung diseases, a study that quantified pleural plaques on computed tomography imaging and its impact on pulmonary function, a study that examined the risk of lung cancer with pleural plaques among two large cohorts and a review of nonasbestos causes of malignant mesothelioma.

SUMMARY: Asbestos-related pulmonary and pleural diseases continue to cause significant morbidity and mortality. This review summarizes the current advances in this field and highlights areas that need additional research.}, } @article {pmid36622824, year = {2022}, author = {Moscadelli, A and Martini, A and Angelini, A and Baldassarre, A and Lorini, C and Bonaccorsi, G and Cacciarini, V and Rosselli, A and Chellini, E}, title = {[Mortality study in a cohort of entertainment workers].}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {44}, number = {3}, pages = {360-359}, pmid = {36622824}, issn = {1592-7830}, mesh = {Humans ; Male ; Female ; Cohort Studies ; *Mesothelioma ; *Occupational Diseases/etiology ; Cause of Death ; *Asbestos ; *Occupational Exposure/adverse effects ; }, abstract = {Introduction. Malignant mesotheliomas have been observed in entertainment workers in the last decades. They have been evaluated as occupationally exposed to asbestos contained in tools used for fireproof and sound-absorbing purposes. Aim of the study. To evaluate the mortality of workers engaged in a Florentine theatre where a large quantity of asbestos was found in the '80s, put in place 20 years earlier. Methods. It is a cohort study on entertainment workers with follow-up period ranged from 1-1-1970 till 31-12-2018. Standardized Mortality Ratios (SMRs) and their 95% Confidence Intervals (95% IC) were calculated by gender and job ("manual workers" and "all other jobs"), using age and sex specific mortality rates of Tuscan population. Results. The cohort includes 826 workers (389 manual workers and 437 engaged in other jobs) engaged by the Florentine theatre between 01/01/1937 and 31/12/1990. Excesses of mortality for all causes are observed in manual workers, either males (301 cases; SMR 304,0; 95% IC 271,5-340,3) or females (86 cases; SMR 429,8; 95% IC 348,0-531,0). The group of the other workers presents deficits of mortality by all causes, cancers and cardiovascular diseases in both genders. One death for pleural cancer is observed in a manual worker. Discussion. The results are in line with previous observations in similar occupations. In the examined Florentine theatre the asbestos exposures were important only for the manual workers who worked in the technical rooms characterized by the presence of friable asbestos sprinkled and in a bad state of maintenance.}, } @article {pmid36612385, year = {2022}, author = {Mutetwa, B and Moyo, D and Brouwer, D}, title = {Prediction of Asbestos-Related Diseases (ARDs) and Chrysotile Asbestos Exposure Concentrations in Asbestos-Cement (AC) Manufacturing Factories in Zimbabwe.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {1}, pages = {}, pmid = {36612385}, issn = {1660-4601}, mesh = {Humans ; Asbestos, Serpentine/toxicity ; *Asbestosis/epidemiology ; Zimbabwe/epidemiology ; *Asbestos ; *Mesothelioma/epidemiology ; *Lung Neoplasms/epidemiology ; *Occupational Exposure ; *Mesothelioma, Malignant ; }, abstract = {The use of historical asbestos measurement data in occupational exposure assessment is essential as it allows more quantitative analysis of possible exposure response relationships in asbestos-related disease (ARD) occurrence. The aim of this study was to predict possible ARDs, namely lung cancer, mesothelioma, gastrointestinal cancer, and asbestosis, in two chrysotile asbestos cement (AC) manufacturing factories. Prediction of ARDs was done using a specific designed job-exposure matrix for airborne chrysotile asbestos fibre concentrations obtained from the Harare and Bulawayo AC factories and through application of OSHA's linear dose effect model in which ARDs were estimated through extrapolation at 1, 10, 20, and 25 years of exposure. The results show that more cancer and asbestosis cases are likely to be experienced among those exposed before 2008 as exposure levels and subsequently cumulative exposure were generally much higher than those experienced after 2008. After a possible exposure period of 25 years, overall cancer cases predicted in the Harare factory were 325 cases per 100,000 workers, while for the Bulawayo factory, 347 cancer cases per 100,000 workers exposed may be experienced. Possible high numbers of ARDs are likely to be associated with specific tasks/job titles, e.g., saw cutting, kollergang, fettling table, ground hard waste, and possibly pipe-making operations, as cumulative exposures, though lower than reported in other studies, may present higher risk of health impairment. The study gives insights into possible ARDs, namely lung cancer, mesothelioma, gastrointestinal cancer, and asbestosis, that may be anticipated at various cumulative exposures over 1, 10, 20, and 25 years of exposure in AC manufacturing factories in Zimbabwe. Additionally, results from the study can also form a basis for more in-depth assessment of asbestos cancer morbidity studies in the AC manufacturing industries.}, } @article {pmid36612122, year = {2022}, author = {Casalone, E and Birolo, G and Pardini, B and Allione, A and Russo, A and Catalano, C and Mencoboni, M and Ferrante, D and Magnani, C and Sculco, M and Dianzani, I and Grosso, F and Mirabelli, D and Filiberti, RA and Rena, O and Sacerdote, C and Rodriguez-Barranco, M and Smith-Byrne, K and Panico, S and Agnoli, C and Johnson, T and Kaaks, R and Tumino, R and Huerta, JM and Riboli, E and Heath, AK and Trobajo-Sanmartín, C and Schulze, MB and Saieva, C and Amiano, P and Agudo, A and Weiderpass, E and Vineis, P and Matullo, G}, title = {Serum Extracellular Vesicle-Derived microRNAs as Potential Biomarkers for Pleural Mesothelioma in a European Prospective Study.}, journal = {Cancers}, volume = {15}, number = {1}, pages = {}, pmid = {36612122}, issn = {2072-6694}, support = {001/WHO_/World Health Organization/International ; MR/S019669/1/MRC_/Medical Research Council/United Kingdom ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive cancer with a dismal prognosis. Early therapeutic interventions could improve patient outcomes. We aimed to identify a pattern of microRNAs (miRNAs) as potential early non-invasive markers of MPM. In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition cohort, we screened the whole miRNome in serum extracellular vesicles (EVs) of preclinical MPM cases. In a subgroup of 20 preclinical samples collected five years prior MPM diagnosis, we observed an upregulation of miR-11400 (fold change (FC) = 2.6, adjusted p-value = 0.01), miR-148a-3p (FC = 1.5, p-value = 0.001), and miR-409-3p (FC = 1.5, p-value = 0.04) relative to matched controls. The 3-miRNA panel showed a good classification capacity with an area under the receiver operating characteristic curve (AUC) of 0.81 (specificity = 0.75, sensitivity = 0.70). The diagnostic ability of the model was also evaluated in an independent retrospective cohort, yielding a higher predictive power (AUC = 0.86). A signature of EV miRNA can be detected up to five years before MPM; moreover, the identified miRNAs could provide functional insights into the molecular changes related to the late carcinogenic process, preceding MPM development.}, } @article {pmid36601180, year = {2022}, author = {Mankidy, B and Sparkman, J and Boddu, S and Huang, Q and Sharma, M}, title = {Simultaneous Use of Endobronchial and Endoscopic Ultrasound Guidance as Primary Tools in the Diagnosis of Malignant Pleural Mesothelioma.}, journal = {Cureus}, volume = {14}, number = {12}, pages = {e32110}, pmid = {36601180}, issn = {2168-8184}, abstract = {Malignant pleural mesothelioma (MPM) is related to exposure to asbestos. It is insidious in nature and is generally diagnosed at an advanced stage. MPM is aggressive and portends a poor prognosis. Definitive diagnosis is usually established by obtaining pathological samples of the pleura by medical or surgical thoracoscopy. However, these procedures are invasive and carry a risk of seeding of biopsy sites with tumors. We herein report an infrequently encountered case of simultaneous use of endobronchial ultrasound and endoscopic ultrasound-guided biopsy of malignant pleural mesothelioma in a 48-year-old female patient.}, } @article {pmid38299094, year = {2023}, author = {Alratrout, H and Boumarah, DN and Alghusnah, ES and Alabbad, A and Alsaffar, AH and Alsafwani, NS and Foula, MS}, title = {Synchronous Malignant Peritoneal Mesothelioma and Sigmoid Adenocarcinoma: a Challenging Clinical Entity.}, journal = {Medical archives (Sarajevo, Bosnia and Herzegovina)}, volume = {77}, number = {5}, pages = {400-404}, pmid = {38299094}, issn = {1986-5961}, mesh = {Humans ; Female ; Aged ; *Mesothelioma/diagnosis/pathology/surgery ; *Mesothelioma, Malignant ; *Peritoneal Neoplasms/diagnosis ; *Colonic Neoplasms/diagnosis ; *Adenocarcinoma/diagnosis/surgery ; }, abstract = {BACKGROUND: Malignant peritoneal mesothelioma (MPM) represents a rare clinical entity. The synchronous existence of MPM with other malignancies as colonic adenocarcinoma have been rarely reported. Its diagnosis and management are challenging given its complexity and rarity.

OBJECTIVE: Herein, we report a case of epithelioid subtype of MPM occurring synchronously with sigmoid colonic adenocarcinoma, along with review of the literature.

CASE PRESENTATION: An elderly female patient was referred as case of rectosigmoid mass. She reported history of abdominal pain, per-rectal bleeding, anorexia, and significant weight loss. Her computed-tomography scan of the abdomen revealed a fistulizing sigmoid mass and multiple enlarged lymphnodes with omental nodulation. The colonoscopy revealed a large fungating mass and the endoscopic biopsies were reported as colonic adenocarcinoma. The patient was scheduled laparoscopic low anterior resection. However, the diagnostic laparoscopy revealed several nodules disseminated all over the peritoneum, suggestive of peritoneal mesothelioma. Therefore, the decision was changed to create transverse colostomy after examination obtaining multiple biopsies from the omental and peritoneal nodules. The histopathological revealed MPM and the final diagnosis was sigmoid adenocarcinoma with synchronous MPM. The patient was started on palliative chemotherapy (capecitabine) without active management of MPM because of her general condition. She was followed up with a good clinical course.

CONCLUSION: MPM is an overlooked entity with vague clinical presentation. Synchronous MPM with colorectal cancer is rare with only few published case reports. Its diagnosis is challenging, and its management should be tailored according to the patient. This case is the first reported case in Saudi Arabia and the Middle East.}, } @article {pmid36556334, year = {2022}, author = {Caraballo-Arias, Y and Zunarelli, C and Caffaro, P and Roccuzzo, F and Nocilla, MR and Imperiale, MC and Romano, C and Boffetta, P and Violante, FS}, title = {Quantitative Assessment of Asbestos Fibers in Normal and Pathological Peritoneal Tissue-A Scoping Review.}, journal = {Life (Basel, Switzerland)}, volume = {12}, number = {12}, pages = {}, pmid = {36556334}, issn = {2075-1729}, abstract = {Peritoneal tissue is the second most affected site by malignant mesothelioma linked to asbestos exposure. This scoping review aims to summarize the findings of the studies in which asbestos fibers in the peritoneum were quantified by electron microscopy, occasionally associated with spectroscopy, both in neoplastic and non-neoplastic tissue. The 9 studies selected comprised 62 cases, out of whom 100 samples were analyzed. Asbestos fibers were detected in 58 samples (58%). In addition, 28 cases had diagnosis of peritoneal mesothelioma. For 32 cases, a lung tumor sample was available: 28/32 samples analyzed presented asbestos fibers; 18/32 reported amphiboles with a range from not detected to 14.2 million fibers per gram of dry tissue (mfgdt); 18/32 reported chrysotile, with a range of 0 to 90 mfgdt. The studies were heterogeneous for type of samples, analytical technology, and circumstances of exposure to asbestos. To evaluate asbestos fibers in the peritoneum and to better understand the association between asbestos exposure and malignant peritoneal mesothelioma, it is desirable that the search for asbestos fibers becomes a routine process every time peritoneal tissue is accessible.}, } @article {pmid36554530, year = {2022}, author = {Gardner, M and Cross, M and Reed, S and Davidson, M and Hughes, R and Oosthuizen, J}, title = {Pathogenic Potential of Respirable Spodumene Cleavage Fragments following Application of Regulatory Counting Criteria for Asbestiform Fibres.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {24}, pages = {}, pmid = {36554530}, issn = {1660-4601}, mesh = {Humans ; Minerals ; *Mesothelioma ; *Mesothelioma, Malignant ; *Lung Neoplasms ; *Occupational Exposure ; }, abstract = {Health risks from exposure to lithium-bearing spodumene cleavage fragments are unknown. While asbestiform fibres can lead to fibrosis, mesothelioma and lung cancer, controversy remains whether non-asbestiform cleavage fragments, having equivalent dimensions, elicit similar pathologic responses. The mineralogy of respirable particles from two alpha (α)-spodumene concentrate grades (chemical and technical) were characterised using semi-quantitative X-ray diffraction (XRD). Particles were measured using scanning electron microscopy (SEM) and the dimensions (length [L], diameter [D], aspect ratio [AR]) applied to regulatory counting criteria for asbestiform fibres. Application of the current World Health Organization (WHO) and National Occupational Health and Safety Commission (NOHSC) counting criteria, L ˃ 5 µm, D ˂ 3 µm, AR ˃ 3:1, to 10 SEM images of each grade identified 47 countable particles in the chemical and 37 in the technical concentrate test samples. Of these particles, 17 and 16 in the chemical and technical test samples, respectively, satisfied the more rigorous, previously used Mines Safety and Inspection Regulations 1995 (Western Australia [WA]) criteria, L ˃ 5 µm and D ≤ 1 µm. The majority of the countable particles were consistent with α-spodumene cleavage fragments. These results suggest elongated α-spodumene particles may pose a health risk. It is recommended the precautionary principle be applied to respirable α-spodumene particles and the identification and control of dust hazards in spodumene extraction, handling and processing industries be implemented.}, } @article {pmid36553016, year = {2022}, author = {Moro, J and Sobrero, S and Cartia, CF and Ceraolo, S and Rapanà, R and Vaisitti, F and Ganio, S and Mellone, F and Rudella, S and Scopis, F and La Paglia, D and Cacciatore, CC and Ruffini, E and Leo, F}, title = {Diagnostic and Therapeutic Challenges of Malignant Pleural Mesothelioma.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {12}, number = {12}, pages = {}, pmid = {36553016}, issn = {2075-4418}, abstract = {Malignant pleural mesothelioma is a rare cancer characterized by a very poor prognosis. Exposure to asbestos is the leading cause of malignant pleural mesothelioma. The preinvasive lesions, the mesothelial hyperplasia and its possible evolution are the focus of the majority of the studies aiming to identify the treatable phase of the disease. The role of BAP-1 and MTAP in the diagnosis of mesothelioma in situ and in the prognosis of malignant pleural mesothelioma is the main topic of recent studies. The management of preinvasive lesions in mesothelioma is still unclear and many aspects are the subject of debate. The diagnosis, the disease staging and the accurate, comprehensive assessment of patients are three key instants for an appropriate management of patients/the disease.}, } @article {pmid36552335, year = {2022}, author = {Rihs, HP and Casjens, S and Raiko, I and Kollmeier, J and Lehnert, M and Nöfer, K and May-Taube, K and Kaiser, N and Taeger, D and Behrens, T and Brüning, T and Johnen, G and , }, title = {Mesothelin Gene Variants Affect Soluble Mesothelin-Related Protein Levels in the Plasma of Asbestos-Exposed Males and Mesothelioma Patients from Germany.}, journal = {Biology}, volume = {11}, number = {12}, pages = {}, pmid = {36552335}, issn = {2079-7737}, abstract = {Malignant mesothelioma (MM) is a severe disease mostly caused by asbestos exposure. Today, one of the best available biomarkers is the soluble mesothelin-related protein (SMRP), also known as mesothelin. Recent studies have shown that mesothelin levels are influenced by individual genetic variability. This study aimed to investigate the influence of three mesothelin (MSLN) gene variants (SNPs) in the 5′-untranslated promoter region (5′-UTR), MSLN rs2235503 C > A, rs3764246 A > G, rs3764247 A > C, and one (rs1057147 G > A) in the 3′-untranslated region (3′-UTR) of the MSLN gene on plasma concentrations of mesothelin in 410 asbestos-exposed males without cancer and 43 males with prediagnostic MM (i.e., with MM diagnosed later on) from the prospective MoMar study, as well as 59 males with manifest MM from Germany. The mesothelin concentration differed significantly between the different groups (p < 0.0001), but not between the prediagnostic and manifest MM groups (p = 0.502). Five to eight mutations of the four SNP variants studied were associated with increased mesothelin concentrations (p = 0.001). The highest mesothelin concentrations were observed for homozygous variants of the three promotor SNPs in the 5′-UTR (p < 0.001), and the highest odds ratio for an elevated mesothelin concentration was observed for MSLN rs2235503 C > A. The four studied SNPs had a clear influence on the mesothelin concentration in plasma. Hence, the analysis of these SNPs may help to elucidate the diagnostic background of patients displaying increased mesothelin levels and might help to reduce false-positive results when using mesothelin for MM screening in high-risk groups.}, } @article {pmid36543384, year = {2022}, author = {Chimed-Ochir, O and Rath, EM and Kubo, T and Yumiya, Y and Lin, RT and Furuya, S and Brislane, K and Klebe, S and Nowak, AK and Kang, SK and Takahashi, K}, title = {Must countries shoulder the burden of mesothelioma to ban asbestos? A global assessment.}, journal = {BMJ global health}, volume = {7}, number = {12}, pages = {}, pmid = {36543384}, issn = {2059-7908}, mesh = {Humans ; Shoulder ; *Mesothelioma/epidemiology/etiology ; *Asbestos/adverse effects ; Policy ; Global Burden of Disease ; }, abstract = {INTRODUCTION: Mesothelioma is a key asbestos-related disease (ARD) but can be difficult to diagnose. Countries presumably ban asbestos to reduce future ARD burdens, but it is unknown if countries ban asbestos as a consequence of ARD burdens. We assessed if and to what extent mesothelioma burden has an impact on a country banning asbestos and obtaining targets for preventative strategies.

METHODS: We analysed the status of asbestos ban and mesothelioma burden during 1990-2019 in 198 countries. We assessed mesothelioma burden by age-adjusted mortality rates (MRs) estimated by the Global Burden of Disease Study (GBD) and mesothelioma identification by the WHO mortality database. For GBD-estimated mesothelioma MR, the pre-ban period in the asbestos-banned countries was compared with the 1990-2019 period in the not-banned countries. For mesothelioma identification, the 1990-2019 period was applied to both banned and not-banned countries.

RESULTS: The association of mesothelioma MR with ban status increased as the ban year approached. Logistic regression analyses showed that the odds of a country banning asbestos increased 14.1-fold (95% CI 5.3 to 37.9) for mesothelioma identification combined with a 26% (12% to 42%) increase per unit increase of mesothelioma MR (one death per million per year) during the period 1-5 year before ban (model p<0.0001).

CONCLUSION: Mesothelioma burden had an impact on, and together with its identification, explained the banning of asbestos in many countries. Asbestos-banned countries likely learnt lessons from their historical policies of using asbestos because mesothelioma burden and identification follow historical asbestos use. Prevention targets for ARD elimination should combine asbestos ban with mesothelioma identification.}, } @article {pmid36541514, year = {2023}, author = {Luo, Y and Akatsuka, S and Motooka, Y and Kong, Y and Zheng, H and Mashimo, T and Imaoka, T and Toyokuni, S}, title = {BRCA1 haploinsufficiency impairs iron metabolism to promote chrysotile-induced mesothelioma via ferroptosis resistance.}, journal = {Cancer science}, volume = {114}, number = {4}, pages = {1423-1436}, pmid = {36541514}, issn = {1349-7006}, support = {JP16H06276 [AdAMS]//Japan Society for the Promotion of Science/ ; JP21H03601//Japan Society for the Promotion of Science/ ; JP19H05462//Japan Society for the Promotion of Science/ ; JP20H05502//Japan Society for the Promotion of Science/ ; JP16H06276//Japan Society for the Promotion of Science/ ; JPMJCR19H4//Core Research for Evolutional Science and Technology/ ; SPRING JPMJSP2125//Japan Science and Technology Agency/ ; }, mesh = {Animals ; Female ; Male ; Rats ; *Asbestos/toxicity ; Asbestos, Crocidolite/toxicity ; Asbestos, Serpentine/toxicity ; BRCA1 Protein/genetics ; Carcinogenesis/genetics ; Comparative Genomic Hybridization ; DNA ; Ferric Compounds/metabolism ; *Ferroptosis/genetics ; Haploinsufficiency ; Iron/metabolism ; *Lung Neoplasms/chemically induced/genetics ; *Mesothelioma, Malignant/chemically induced/genetics ; }, abstract = {Malignant mesothelioma (MM) is still a social burden associated with asbestos exposure. Local iron accumulation thereby represents the major pathogenesis, followed by oxidative DNA strand breaks and genomic alterations in the mesothelium. BRCA1 is a critical component of homologous recombination repair directed to DNA double-stranded breaks, whereas BRCA1 germline mutation is an established risk for breast/ovarian cancer, its role in MM development remains to be elucidated. Murine Brca1 mutant models so far have not reproduced human phenotypes. However, a rat Brca1 mutant model (Mut; L63X/+) recently reproduced them at least partially. Here we describe the differential induction of MM in Brca1 mutant rats by intraperitoneal injection of chrysotile or crocidolite. Only Mut males injected with chrysotile revealed a promotional effect on mesothelial carcinogenesis in comparison with wild-type and/or females, with all the MMs Brca1 haploinsufficient. Array-based comparative genomic hybridization of MMs disclosed a greater extent of chromosomal deletions in Brca1 mutants, including Cdkn2a/2b accompanied by Tfr2 amplification, in comparison with wild-type tumors. Mutant MMs indicated iron metabolism dysregulation, such as an increase in catalytic Fe(II) and Ki67-index as well as a decrease in Fe(III) and ferritin expression. Simultaneously, mutant MMs revealed ferroptosis resistance by upregulation of Slc7A11 and Gpx4. At an early carcinogenic stage of 4 weeks, induced Brca1 expression in mesothelial cells was significantly suppressed in chrysotile/Mut in comparison with crocidolite/Mut, whereas significant preference to iron with a decrease in Fe(III) has been already established. In conclusion, chrysotile exposure can be a higher risk for MM in BRCA1 mutant males, considering the rat results.}, } @article {pmid36525994, year = {2023}, author = {Gazzano, E and Petriglieri, JR and Aldieri, E and Fubini, B and Laporte-Magoni, C and Pavan, C and Tomatis, M and Turci, F}, title = {Cytotoxicity of fibrous antigorite from New Caledonia.}, journal = {Environmental research}, volume = {230}, number = {}, pages = {115046}, doi = {10.1016/j.envres.2022.115046}, pmid = {36525994}, issn = {1096-0953}, mesh = {Humans ; Mice ; Animals ; *Asbestos, Serpentine/toxicity ; New Caledonia ; *Asbestos/toxicity ; Minerals/toxicity ; Silicates ; }, abstract = {Exposure to asbestos and asbestos-like minerals has been related to the development of severe lung diseases, including cancer and malignant mesothelioma (MM). A high incidence of non-occupational MM was observed in New Caledonia (France) in people living in proximity of serpentinite outcrops, containing chrysotile and fibrous antigorite. Antigorite is a magnesium silicate, which shares with chrysotile asbestos the chemical formula. To achieve information on antigorite toxicity, we investigated the physico-minero-chemical features relevant for toxicity and cellular effects elicited on murine macrophages (MH-S) and alveolar epithelial cells (A549) of three fibrous antigorites (f-Atg) collected in a Caledonian nickel lateritic ore and subjected to supergene alteration. Field Atg were milled to obtain samples suitable for toxicological studies with a similar particle size distribution. UICC chrysotile (Ctl) and a non-fibrous antigorite (nf-Atg) were used as reference minerals. A high variability in toxicity was observed depending on shape, chemical alteration, and surface reactivity. The antigorites shared with Ctl a similar surface area (16.3, 12.1, 20.3, 13.4, and 15.6 m[2]/g for f-Atg1, 2, 3, nf-Atg, and Ctl). f-Atg showed different level of pedogenetic weathering (Ni depletion f-Atg1 ≪ f-Atg2 and 3) and contained about 50% of elongated mineral particles, some of which exhibited high aspect ratios (AR > 10 μm, 20%, 26%, 31% for f-Atg1, 2, and 3, respectively). The minerals differed in bio-accessible iron at pH 4.5 (f-Atg1 ≪ f-Atg3, < f-Atg2, nf-Atg < Ctl), and surface reactivity (ROS release in solution, f-Atg1 ≪ f-Atg2, 3, nf-Atg, and Ctl). f-Atg2 and f-Atg3 induced oxidative stress and pro-inflammatory responses, while the less altered, poorly reactive sample (f-Atg1) induced negligible effects, as well nf-Atg. The slow dissolution kinetics observed in simulated body fluids may signal a high biopersistence. Overall, our work revealed a significative cellular toxicity of f-Atg that correlates with fibrous habit and surface reactivity.}, } @article {pmid36519024, year = {2022}, author = {Klotz, LV and Hoffmann, H and Shah, R and Eichhorn, F and Gruenewald, C and Bulut, EL and Griffo, R and Muley, T and Christopoulos, P and Baum, P and Huber, P and Safi, S and Kriegsmann, M and Thomas, M and Bischoff, H and Winter, H and Eichhorn, ME}, title = {Multimodal therapy of epithelioid pleural mesothelioma: improved survival by changing the surgical treatment approach.}, journal = {Translational lung cancer research}, volume = {11}, number = {11}, pages = {2230-2242}, pmid = {36519024}, issn = {2218-6751}, abstract = {BACKGROUND: The exact role and type of surgery for malignant pleural mesothelioma (MPM) remains controversial. This study aimed at analyzing a 20-year single center perioperative experience in MPM surgery at our high-volume thoracic surgery center and comparing the overall survival after trimodal extrapleural pneumonectomy (EPP) and extended pleurectomy and decortication combined with hyperthermic intrathoracic chemoperfusion (EPD/HITOC) and adjuvant chemotherapy with that after chemotherapy (CTx) alone.

METHODS: Patients with epithelioid MPM treated with neoadjuvant chemotherapy, EPP and adjuvant radiotherapy within a trimodal concept or EPD/HITOC in combination with adjuvant chemotherapy between 2001 and 2018 were included in this retrospective analysis. Surgical cohorts were compared to patients treated with standard chemotherapy.

RESULTS: Overall, 182 patients (69 EPP, 57 EPD/HITOC, 56 CTx) were analyzed. Due to occupational exposure to asbestos for most of the patients, 154 patients (84.6%) were male. The patients in the surgical cohorts were significantly younger than those in the CTx cohort. There was no significant difference between the proportion of patient age and side. The median overall survival of the EPD/HITOC cohort with 38.1 months was significantly longer than that of the EPP and CTx cohorts (24.0 and 15.8 months). Better survival was significantly associated with an ECOG 0 performance status, age below 70 years, and negative lymph node status. In the multivariate analysis, EPD/HITOC was significantly associated with improved overall survival. Perioperative morbidity was lower in the EPD/HITOC group than in the EPP cohort.

CONCLUSIONS: EPD/HITOC is feasible and safe for localized epithelioid pleural mesothelioma. Changing the surgical approach to a less radical lung-sparing technique may improve overall survival compared to trimodal EPP.}, } @article {pmid36506969, year = {2022}, author = {Guglielmucci, F and Bonafede, M and Azzolina, D and Marinaccio, A and Franzoi, IG and Migliore, E and Mensi, C and Chellini, E and Romeo, E and Grosso, F and Granieri, A}, title = {Preliminary validation of a brief PROM assessing psychological distress in patients with malignant mesothelioma: The mesothelioma psychological distress tool-Patients.}, journal = {Frontiers in psychology}, volume = {13}, number = {}, pages = {974982}, pmid = {36506969}, issn = {1664-1078}, abstract = {OBJECTIVE: Psychological suffering in malignant mesothelioma (MM) differs from that in other cancers because of its occupational etiology, and we aimed to develop specific patient-reported outcome measures to assess it.

METHODS: We used a multi-method prospective observational multicentric study (N = 149), and a preliminary questionnaire validation was performed through a Bayesian approach.

RESULTS: Item analysis showed a good internal consistency and reliability (Cronbach alpha = 0.79 [95% CI = 0.74-0.93]. Twenty of the 41 initial items were selected as posterior 95% highest density interval factor loading standardized effect size fell outside of the region of practical equivalence. Bayesian exploratory factor analysis showed a two-factor structure: (1) Trauma-related reactions (TR, 13 items) and (2) Claim for justice (CJ, 7 items), confirmed by the Bayesian confirmatory factor analysis. Latent factors were poorly correlated (Posterior median: 0.13; 95% CI = -0.079 to 0.323). The 90% root mean square error of approximation posterior median was 0.04 [90% CI = 0.03-0.58]; the 90% chi-square posterior median was 242 [90% CI = 209-287].

CONCLUSION: Psychological suffering in MM patients implies negative cognitive, emotional, and somatic reactions related to the traumatic impact of the disease and the need to obtain justice through economic compensation. Our findings provide preliminary evidence that the Mesothelioma Psychological Distress Tool-Patients could be a promising and reliable instrument to assess MM patients' psychological distress.}, } @article {pmid36499762, year = {2022}, author = {Munson, P and Shukla, A}, title = {Potential Roles of Exosomes in the Development and Detection of Malignant Mesothelioma: An Update.}, journal = {International journal of molecular sciences}, volume = {23}, number = {23}, pages = {}, pmid = {36499762}, issn = {1422-0067}, support = {R01 ES021110/ES/NIEHS NIH HHS/United States ; W81XWH-13-PRCRP-IA//Department of Defence/ ; ES021110/NH/NIH HHS/United States ; }, mesh = {Humans ; *Mesothelioma, Malignant ; *Mesothelioma/pathology ; *Lung Neoplasms/pathology ; *Asbestos/toxicity ; *Exosomes/pathology ; }, abstract = {Malignant mesothelioma (MM) is a devastating cancer of mesothelial cells, caused by asbestos exposure. Limited knowledge regarding the detection of asbestos exposure and the early diagnosis of MM, as well as a lack of successful treatment options for this deadly cancer, project an immediate need to understand the mechanism(s) of MM development. With the recent discovery of nano-vesicles, namely exosomes, and their enormous potential to contain signature molecules representative of different diseases, as well as to communicate with distant targets, we were encouraged to explore their role(s) in MM biology. In this review, we summarize what we know so far about exosomes and MM based on our own studies and on published literature from other groups in the field. We expect that the information contained in this review will help advance the field of MM forward by revealing the mechanisms of MM development and survival. Based on this knowledge, future therapeutic strategies for MM can potentially be developed. We also hope that the outcome of our studies presented here may help in the detection of MM.}, } @article {pmid36498008, year = {2022}, author = {Huh, DA and Chae, WR and Choi, YH and Kang, MS and Lee, YJ and Moon, KW}, title = {Disease Latency according to Asbestos Exposure Characteristics among Malignant Mesothelioma and Asbestos-Related Lung Cancer Cases in South Korea.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {23}, pages = {}, pmid = {36498008}, issn = {1660-4601}, mesh = {Humans ; *Mesothelioma, Malignant ; *Asbestos/toxicity ; *Mesothelioma/epidemiology/etiology ; *Lung Neoplasms/chemically induced/epidemiology ; Republic of Korea/epidemiology ; *Occupational Exposure ; }, abstract = {Korea was one of the major consumers of asbestos in the late 1900s, and asbestos-related disease patients have been reported continuously to date, owing to long disease latency. Several studies have been conducted to predict the future incidence of malignant mesothelioma and lung cancer in Korea, but little is understood about the latency time. Therefore, the aim of this study is to estimate the latency period of malignant mesothelioma and asbestos-related lung cancer in Korea and its determinants. We obtained information from the Environmental Health Centers for Asbestos in Korea on the history of asbestos exposure and demographic characteristics of 1933 patients with malignant mesothelioma and asbestos-related lung cancer. In our study, the latency periods for malignant mesothelioma and lung cancer were 33.7 and 40.1 years, respectively. Regardless of the disease type, those with a history of exposure related to the production of asbestos-containing products or asbestos factories had the shortest latency period. In addition, we observed that those who worked in or lived near asbestos mines tended to have a relatively long disease latency. Smoking was associated with shorter latency, but no linear relationship between the lifetime smoking amount (expressed in pack years) and latent time was observed. In addition, the age of initial exposure showed a negative linear association with the latency period for mesothelioma and lung cancer.}, } @article {pmid36475505, year = {2022}, author = {Ferrari, L and Iodice, S and Cantone, L and Dallari, B and Dioni, L and Bordini, L and Palleschi, A and Mensi, C and Pesatori, AC}, title = {Identification of a new potential plasmatic biomarker panel for the diagnosis of malignant pleural mesothelioma.}, journal = {La Medicina del lavoro}, volume = {113}, number = {6}, pages = {e2022052}, pmid = {36475505}, issn = {0025-7818}, mesh = {Humans ; *Mesothelioma, Malignant ; *HMGB1 Protein ; Reproducibility of Results ; *MicroRNAs ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare highly aggressive tumor strongly associated with asbestos exposure and characterized by poor prognosis. Currently, diagnosis is based on invasive techniques, thus there is a need of identifying non-invasive biomarkers for early detection of the disease among asbestos-exposed subjects. In the present study, we measured the plasmatic concentrations of Mesothelin, Fibulin-3, and HMGB1 protein biomarkers, and of hsa-miR-30e-3p and hsa-miR-103a-3p Extracellular-Vesicles- embedded micro RNAs (EV-miRNAs). We tested the ability of these biomarkers to discriminate between MPM and PAE subjects alone and in combination.

METHODS: the study was conducted on a population of 26 patients with MPM and 54 healthy subjects with previous asbestos exposure (PAE). Mesothelin, Fibulin-3, and HMGB1 protein biomarkers were measured by the enzyme-linked immunosorbent assay (ELISA) technique; the levels of hsa-miR-30e-3p and hsa-miR-103a-3p EV-miRNAs was assessed by quantitative real-time PCR (qPCR).

RESULTS: the most discriminating single biomarker resulted to be Fibulin-3 (AUC 0.94 CI 95% 0.88-1.0; Sensitivity 88%; Specificity 87%). After investigating the different possible combinations, the best performance was obtained by the three protein biomarkers Mesothelin, Fibulin-3, and HMGB1 (AUC 0.99 CI 95% 0.97-1.0; Sensitivity 96%; Specificity 93%).

CONCLUSIONS: the results obtained contribute to identifying new potential non-invasive biomarkers for the early diagnosis of MPM in high-risk asbestos-exposed subjects. Further studies are needed to validate the evidence obtained, in order to assess the reliability of the proposed biomarker panel.}, } @article {pmid36466911, year = {2022}, author = {Graham, PT and Nowak, AK and Cornwall, SMJ and Larma, I and Nelson, DJ}, title = {The STING agonist, DMXAA, reduces tumor vessels and enhances mesothelioma tumor antigen presentation yet blunts cytotoxic T cell function in a murine model.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {969678}, pmid = {36466911}, issn = {1664-3224}, mesh = {Mice ; Animals ; T-Lymphocytes, Cytotoxic ; Antigen Presentation ; Disease Models, Animal ; *Mesothelioma, Malignant ; *Mesothelioma/drug therapy ; Ovalbumin ; Antigens, Neoplasm ; }, abstract = {We assessed the murine Stimulator of Interferon Genes (STING) agonist, DMXAA, for anti-mesothelioma potential using the AE17-sOVA model that expresses ovalbumin (OVA) as a neo tumor antigen. Dose response experiments alongside testing different routes of administration identified a safe effective treatment regimen that induced 100% cures in mice with small or large tumors. Three doses of 25mg/kg DMXAA given intra-tumorally every 9 days induced tumor regression and long-term survival (>5 months). Re-challenge experiments showed that tumor-free mice developed protective memory. MTT and propidium-iodide assays showed that DMXAA exerted direct cytotoxic effects at doses >1mg/ml on the murine AE17 and AB1 mesothelioma cell lines. In-vivo studies using a CFSE-based in-vivo proliferation assay showed that DMXAA improved tumor-antigen presentation in tumor-draining lymph nodes, evidenced by OVA-specific OT-1 T cells undergoing more divisions. An in-vivo cytotoxic T lymphocyte (CTL) assay showed that DMXAA blunted the lytic quality of CTLs recognizing the dominant (SIINFEKL) and a subdominant (KVVRFDKL) OVA epitopes. DMXAA reduced tumor vessel size in-vivo and although the proportion of T cells infiltrating tumors reduced, the proportion of tumor-specific T cells increased. These data show careful dosing and treatment protocols reduce mesothelioma cell viability and modulate tumor vessels such that tumor-antigen specific CTLs access the tumor site. However, attempts to enhance DMXAA-induced anti-tumor responses by combination with an agonist anti-CD40 antibody or IL-2 reduced efficacy. These proof-of-concept data suggest that mesothelioma patients could benefit from treatment with a STING agonist, but combination with immunotherapy should be cautiously undertaken.}, } @article {pmid36465873, year = {2022}, author = {Patel, JP and Brook, MS and Kah, M and Hamilton, A}, title = {Global geological occurrence and character of the carcinogenic zeolite mineral, erionite: A review.}, journal = {Frontiers in chemistry}, volume = {10}, number = {}, pages = {1066565}, pmid = {36465873}, issn = {2296-2646}, abstract = {As with the six regulated asbestos minerals (chrysotile, amosite, crocidolite, anthophyllite, tremolite, and actinolite), the zeolite mineral, erionite, can exhibit a fibrous morphology. When fibrous erionite is aerosolized and inhaled, it has been linked to cases of lung cancers, such as malignant mesothelioma. Importantly, fibrous erionite appears to be more carcinogenic than the six regulated asbestos minerals. The first health issues regarding erionite exposure were reported in Cappadocia (Turkey), and more recently, occupational exposure issues have emerged in the United States. Erionite is now classified as a Group 1 carcinogen. Thus, identifying the geological occurrence of erionite is a prudent step in determining possible exposure pathways, but a global review of the geological occurrence of erionite is currently lacking. Here, we provide a review of the >100 global locations where erionite has been reported, including: 1) geological setting of host rocks; 2) paragenetic sequence of erionite formation, including associated zeolite minerals; 3) fiber morphological properties and erionite mineral series (i.e., Ca, K, Na); and 4) a brief overview of the techniques that have been used to identify and characterize erionite. Accordingly, erionite has been found to commonly occur within two major rock types: felsic and mafic. Within felsic rocks (in particular, tuffaceous layers within lacustrine paleoenvironments), erionite is disseminated through the layer as a cementing matrix. In contrast, within mafic (i.e., basaltic) rocks, erionite is typically found within vesicles. Nevertheless, aside from detailed studies in Italy and the United States, there is a paucity of specific information on erionite geological provenance or fiber morphology. The latter issue is a significant drawback given its impact on erionite toxicity. Future erionite studies should aim to provide more detailed information, including variables such as rock type and lithological properties, quantitative geochemistry, and fiber morphology.}, } @article {pmid36429481, year = {2022}, author = {Handra, CM and Chirila, M and Smarandescu, RA and Ghita, I}, title = {Near Missed Case of Occupational Pleural Malignant Mesothelioma, a Case Report and Latest Therapeutic Options.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {22}, pages = {}, pmid = {36429481}, issn = {1660-4601}, mesh = {Humans ; *Mesothelioma, Malignant ; *Mesothelioma/chemically induced/diagnosis/therapy ; *Pleural Neoplasms/diagnosis/therapy/complications ; *Asbestos/adverse effects ; *Occupational Exposure/adverse effects ; }, abstract = {Asbestos use started to be gradually banned in Europe from 1991 onwards, and there are currently strict occupational exposure limits for asbestos. However, malignant mesothelioma has a long latency time (in some cases up to 50-60 years), so the risks related to asbestos exposure should not be forgotten. Considering the increased risk of lung cancer following the inhalation of asbestos fibers, lifetime health monitoring should be considered in people occupationally exposed to asbestos, with an emphasis on the respiratory system. An assessment of their occupational history should be performed rigorously, especially in the areas with a history of asbestos production/use, as this is a key element for an early diagnosis and appropriate treatment. This case report presents a near-missed case of occupational pleural malignant mesothelioma. The latency time between the first asbestos exposure and the diagnosis of occupational pleural malignant mesothelioma was 49 years. The accurate diagnosis was made two years after the first symptoms appeared.}, } @article {pmid36420194, year = {2022}, author = {Keam, S and MacKinnon, KM and D'Alonzo, RA and Gill, S and Ebert, MA and Nowak, AK and Cook, AM}, title = {Effects of Photon Radiation on DNA Damage, Cell Proliferation, Cell Survival, and Apoptosis of Murine and Human Mesothelioma Cell Lines.}, journal = {Advances in radiation oncology}, volume = {7}, number = {6}, pages = {101013}, pmid = {36420194}, issn = {2452-1094}, abstract = {PURPOSE: To characterize the cellular responses of murine and human mesothelioma cell lines to different doses of photon radiation with a long-term aim of optimizing a clinically relevant in vivo model in which to study the interaction of radiation therapy and immunotherapy combinations.

METHODS AND MATERIALS: Two murine mesothelioma cell lines (AB1 and AE17) and 3 human cell lines (BYE, MC, and JU) were used in the study. Cells were treated with increasing doses of photon radiation. DNA damage, DNA repair, cell proliferation, and apoptosis at different time points after irradiation were quantified by flow cytometry, and cell survival probability was examined using clonogenic survival assay.

RESULTS: DNA damage increased with escalating dose in all cell lines. Evident G2/M arrest and reduced cell proliferation were observed after irradiation with 8 Gy. DNA repair was uniformly less efficient at higher compared with lower radiation-fraction doses. The apoptosis dose response varied between cell lines, with greater apoptosis observed at 16 Gy with human BYE and murine AB1 cell lines but less for other studied cell lines, regardless of dose and time. The α/β ratio from the cell survival fraction of human mesothelioma cell lines was smaller than from murine ones, suggesting human cell lines in our study were more sensitive to a change of dose per fraction than were murine mesothelioma cell lines. However, in all studied cell lines, colony formation was completely inhibited at 8 Gy.

CONCLUSIONS: A threshold dose of 8 Gy appeared to be appropriate for hypofractionated radiation therapy. However, the radiation therapy doses between 4 and 8 Gy remain to be systematically analyzed. These observations provide an accurate picture of the in vitro response of mesothelioma cell lines to photon irradiation and characterize the heterogeneity between human and murine cell lines. This information may guide in vivo experiments and the strengths and limitations of extrapolation from murine experimentation to potential human translation.}, } @article {pmid36420072, year = {2022}, author = {Yabuuchi, Y and Hiroshima, K and Oshima, H and Kanazawa, J and Hayashihara, K and Nakagawa, T and Shimanouchi, M and Usui, S and Oh-Ishi, S and Saito, T and Hizawa, N and Minami, Y}, title = {Usefulness of malignant pleural effusion for early cytological diagnosis of mesothelioma in situ: A case report.}, journal = {Oncology letters}, volume = {24}, number = {6}, pages = {440}, pmid = {36420072}, issn = {1792-1082}, abstract = {Mesothelioma in situ (MIS) is defined as a preinvasive mesothelioma that forms a single layer of mild atypical mesothelial cells lining on the serosa surface of pleura. The atypical mesothelial cells present loss of BRCA-1 associated protein-1 (BAP-1) and/or methylthioadenosine phosphorylase as examined by immunohistochemistry (IHC) and/or homozygous deletion of cyclin-dependent kinase inhibitor 2A/p16 as examined by fluorescence in situ hybridization. It is difficult to diagnose because of the unremarkable clinical findings except for pleural effusion. The present report describes a case in which MIS was diagnosed at the time of sampling due to the presence of clearly malignant mesothelial cells in the pleural fluid. In 2016, a 74-year-old man with a history of past exposure to asbestos was admitted to Ibaraki Higashi National Hospital (Tokai-mura, Japan) with dyspnea. Chest CT indicated only right pleural effusion. Malignant mesothelial cells were suspected in a cell block made using pleural effusion; therefore, right pleural biopsy was performed. Pathologically, there was proliferation of mesothelial cells with mild atypia that formed a single-flat layer on the pleural surface; however, there was no invasion. Furthermore, IHC revealed loss of BAP-1 in cells from the biopsied pleura and pleural effusion. MIS was suspected at the time; however, the patient arbitrarily quit his medical check-ups. After 44 months, the patient was readmitted to our hospital complaining of dyspnea. CT indicated a large right pleural mass. A specimen of the mass obtained via CT-guided needle biopsy revealed malignant mesothelioma. The patient continued to deteriorate and eventually died. This case indicated that pleural effusion could be used to demonstrate overtly malignant mesothelial cells and diagnose MIS at the time of sampling. To the best of our knowledge, this is first report of MIS with overtly malignant mesothelial cells in pleural effusion. Pleural effusion may serve an important role in MIS diagnosis.}, } @article {pmid36410050, year = {2022}, author = {Walter, M and Schenkeveld, WDC and Tomatis, M and Schelch, K and Peter-Vörösmarty, B and Geroldinger, G and Gille, L and Bruzzoniti, MC and Turci, F and Kraemer, SM and Grusch, M}, title = {The Potential Contribution of Hexavalent Chromium to the Carcinogenicity of Chrysotile Asbestos.}, journal = {Chemical research in toxicology}, volume = {35}, number = {12}, pages = {2335-2347}, pmid = {36410050}, issn = {1520-5010}, mesh = {Humans ; Asbestos, Serpentine/toxicity/chemistry ; Hydrogen Peroxide ; *Asbestos ; Chromium/toxicity ; Carcinogens/analysis ; *Lung Neoplasms/chemically induced ; }, abstract = {Chrysotile asbestos is a carcinogenic mineral that has abundantly been used in industrial and consumer applications. The carcinogenicity of the fibers is partly governed by reactive Fe surface sites that catalyze the generation of highly toxic hydroxyl radicals (HO[•]) from extracellular hydrogen peroxide (H2O2). Chrysotile also contains Cr, typically in the low mass permille range. In this study, we examined the leaching of Cr from fibers at the physiological lung pH of 7.4 in the presence and absence of H2O2. Furthermore, we investigated the potential of cells from typical asbestos-burdened tissues and cancers to take up Cr leached from chrysotile in PCR expression, immunoblot, and cellular Cr uptake experiments. Finally, the contribution of Cr to fiber-mediated H2O2 decomposition and HO[•] generation was studied. Chromium readily dissolved from chrysotile fibers in its genotoxic and carcinogenic hexavalent redox state upon oxidation by H2O2. Lung epithelial, mesothelial, lung carcinoma, and mesothelioma cells expressed membrane-bound Cr(VI) transporters and accumulated Cr up to 10-fold relative to the Cr(VI) concentration in the spiked medium. Conversely, anion transporter inhibitors decreased cellular Cr(VI) uptake up to 45-fold. Finally, chromium associated with chrysotile neither decomposed H2O2 nor contributed to fiber-mediated HO[•] generation. Altogether, our results support the hypothesis that Cr may leach from inhaled chrysotile in its hexavalent state and subsequently accumulate in cells of typically asbestos-burdened tissues, which could contribute to the carcinogenicity of chrysotile fibers. However, unlike Fe, Cr did not significantly contribute to the adverse radical production of chrysotile.}, } @article {pmid36387076, year = {2022}, author = {Chang, F and Keam, S and Hoang, TS and Creaney, J and Gill, S and Nowak, AK and Ebert, M and Cook, AM}, title = {Immune marker expression of irradiated mesothelioma cell lines.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {1020493}, pmid = {36387076}, issn = {2234-943X}, abstract = {BACKGROUND: Though immune checkpoint inhibition has recently shown encouraging clinical efficacy in mesothelioma, most patients do not respond. Combining immune checkpoint inhibition with radiotherapy presents an attractive option for improving treatment responses owing to the various immunomodulatory effects of radiation on tumors. However, the ideal dosing and scheduling of combined treatment remains elusive, as it is poorly studied in mesothelioma. The present study characterizes the dose- and time-dependent changes to expression of various immune markers and cytokines important to antitumor responses following irradiation of mesothelioma cell lines.

METHODS: Two murine (AB1, AE17) and two human (BYE, JU77) mesothelioma cell lines were treated with titrated gamma-radiation doses (1-8 Gy) and the expression of MHC class-I, MHC class-II and PD-L1 was measured over a series of post-irradiation timepoints (1-72 hours) by flow cytometry. Levels of cytokines IL-1α, IL-1β, IL-6, IL-10, IL-12p70, IL-17A, IL-23, IL-27, MCP-1, IFN-β, IFN-γ, TNF-α, and GM-CSF were measured by multiplex immunoassay in murine cell lines following 8 Gy radiation.

RESULTS: Following irradiation, a dose-dependent upregulation of MHC-I and PD-L1 was observed on three of the four cell lines studied to varying extents. For all cell lines, the increase in marker expression was most pronounced 72 hours after radiation. At this timepoint, increases in levels of cytokines IFN-β, MCP-1 and IL-6 were observed following irradiation with 8 Gy in AB1 but not AE17, reflecting patterns in marker expression.

CONCLUSIONS: Overall, this study establishes the dose- and time-dependent changes in immune marker expression of commonly studied mesothelioma cell lines following radiation and will inform future study into optimal dosing and scheduling of combined radiotherapy and immune checkpoint inhibition for mesothelioma.}, } @article {pmid36362413, year = {2022}, author = {Crovella, S and Moura, RR and Brandão, L and Vita, F and Schneider, M and Zanconati, F and Finotto, L and Zacchi, P and Zabucchi, G and Borelli, V}, title = {Variant Enrichment Analysis to Explore Pathways Disruption in a Necropsy Series of Asbestos-Exposed Shipyard Workers.}, journal = {International journal of molecular sciences}, volume = {23}, number = {21}, pages = {}, pmid = {36362413}, issn = {1422-0067}, support = {(Bando di Ricerca sanitaria 2017-programma 5 per mille anno 2015) and Municipality of Monfalcone (Gorizia)//Italian League for the Fight Against Cancer (LILT), ASSOCIAZIONE ISONTINA LILT/ ; decree 1124/SPS, 09/20/2016, N° 1299//Regione Autonoma Friuli-Venezia Giulia, Assessorato alla Salute e Protezione Sociale, LR 22/2001/ ; BioHub 03/20//Institute for Maternal and Child Health IRCCS "Burlo Garofolo/Italian Ministry of Health"/ ; 311415/2020-2//Interreg Italia-Slovenia, ISE-EMH 07/2019; and by CNPq/ ; }, mesh = {Humans ; Autopsy ; *Asbestos/toxicity ; *Mesothelioma/chemically induced/genetics ; *Mesothelioma, Malignant ; *Lung Neoplasms/chemically induced/genetics ; *Occupational Exposure/adverse effects ; }, abstract = {The variant enrichment analysis (VEA), a recently developed bioinformatic workflow, has been shown to be a valuable tool for whole-exome sequencing data analysis, allowing finding differences between the number of genetic variants in a given pathway compared to a reference dataset. In a previous study, using VEA, we identified different pathway signatures associated with the development of pulmonary toxicities in mesothelioma patients treated with radical hemithoracic radiation therapy. Here, we used VEA to discover novel pathways altered in individuals exposed to asbestos who developed or not asbestos-related diseases (lung cancer or mesothelioma). A population-based autopsy study was designed in which asbestos exposure was evaluated and quantitated by investigating objective signs of exposure. We selected patients with similar exposure to asbestos. Formalin-fixed paraffin-embedded (FFPE) tissues were used as a source of DNA and whole-exome sequencing analysis was performed, running VEA to identify potentially disrupted pathways in individuals who developed thoracic cancers induced by asbestos exposure. By using VEA analysis, we confirmed the involvement of pathways considered as the main culprits for asbestos-induced carcinogenesis: oxidative stress and chromosome instability. Furthermore, we identified protective genetic assets preserving genome stability and susceptibility assets predisposing to a worst outcome.}, } @article {pmid36362209, year = {2022}, author = {Paajanen, J and Bueno, R and De Rienzo, A}, title = {The Rocky Road from Preclinical Findings to Successful Targeted Therapy in Pleural Mesothelioma.}, journal = {International journal of molecular sciences}, volume = {23}, number = {21}, pages = {}, pmid = {36362209}, issn = {1422-0067}, mesh = {Humans ; *Lung Neoplasms/drug therapy/genetics/chemically induced ; *Mesothelioma/drug therapy/genetics/chemically induced ; *Mesothelioma, Malignant ; *Pleural Neoplasms/drug therapy/genetics ; *Asbestos/adverse effects ; Ubiquitin Thiolesterase/genetics ; }, abstract = {Pleural mesothelioma (PM) is a rare and aggressive disease that arises from the mesothelial cells lining the pleural cavity. Approximately 80% of PM patients have a history of asbestos exposure. The long latency period of 20-40 years from the time of asbestos exposure to diagnosis, suggests that multiple somatic genetic alterations are required for the tumorigenesis of PM. The genomic landscape of PM has been characterized by inter- and intratumor heterogeneity associated with the impairment of tumor suppressor genes such as CDKN2A, NF2, and BAP1. Current systemic therapies have shown only limited efficacy, and none is approved for patients with relapsed PM. Advances in understanding of the molecular landscape of PM has facilitated several biomarker-driven clinical trials but so far, no predictive biomarkers for targeted therapies are in clinical use. Recent advances in the PM genetics have provided optimism for successful molecular strategies in the future. Here, we summarize the molecular mechanism underlying PM pathogenesis and review potential therapeutic targets.}, } @article {pmid36361401, year = {2022}, author = {Vorster, T and Mthombeni, J and teWaterNaude, J and Phillips, JI}, title = {The Association between the Histological Subtypes of Mesothelioma and Asbestos Exposure Characteristics.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {21}, pages = {}, pmid = {36361401}, issn = {1660-4601}, mesh = {Humans ; Female ; *Mesothelioma, Malignant ; *Asbestos ; *Mesothelioma/epidemiology ; Asbestos, Crocidolite/toxicity ; Mining ; *Occupational Exposure ; *Occupational Diseases/epidemiology ; *Lung Neoplasms/pathology ; }, abstract = {Asbestos mining operations have left South Africa with a legacy of asbestos contamination and asbestos-related diseases continue to be a problem. The large-scale mining of three types of asbestos presents a unique opportunity to study malignant mesothelioma of the pleura (mesothelioma) in South Africa. This study aimed to describe the demographics of deceased individuals diagnosed with mesothelioma and explore any associations between the histological morphology of mesothelioma and asbestos characteristics. We reviewed the records of all deceased miners and ex-miners from the Pathology Automation System (PATHAUT) database of the National Institute of Occupational Health (NIOH) that were histologically diagnosed with mesothelioma in the period from January 2006-December 2016 (11 years). The study population does not include all cases of mesothelioma in South Africa but rather those that reached the compensation system. Crocidolite asbestos fibres were identified in the majority of mesothelioma cases (n = 140; 53.4%). The epithelioid subtype was most commonly present in both occupational and environmental cases. Cases with the sarcomatous subtype were older at death and fewer female cases were diagnosed with this subtype. No relationship between mesothelioma subtype and asbestos type or asbestos burden or fibre size was established.}, } @article {pmid36357176, year = {2023}, author = {Azzolina, D and Consonni, D and Ferrante, D and Mirabelli, D and Silvestri, S and Luberto, F and Angelini, A and Cuccaro, F and Nannavecchia, AM and Oddone, E and Vicentini, M and Barone-Adesi, F and Cena, T and Mangone, L and Roncaglia, F and Sala, O and Menegozzo, S and Pirastu, R and Tunesi, S and Chellini, E and Miligi, L and Perticaroli, P and Pettinari, A and Bressan, V and Merler, E and Girardi, P and Bisceglia, L and Marinaccio, A and Massari, S and Magnani, C and , }, title = {Rate advancement measurement for lung cancer and pleural mesothelioma in asbestos-exposed workers.}, journal = {Thorax}, volume = {78}, number = {8}, pages = {808-815}, doi = {10.1136/thorax-2021-217862}, pmid = {36357176}, issn = {1468-3296}, mesh = {Humans ; *Asbestos/toxicity ; Cohort Studies ; Italy/epidemiology ; *Lung Neoplasms/epidemiology/mortality ; *Mesothelioma/epidemiology/mortality ; Mortality/trends ; *Occupational Diseases/epidemiology/mortality ; *Occupational Exposure/adverse effects ; *Pleural Neoplasms/epidemiology/mortality ; Risk Assessment ; Male ; Female ; Construction Industry ; Adult ; Middle Aged ; Aged ; }, abstract = {INTRODUCTION: Exposure to asbestos increases the risk of lung cancer and mesothelioma. Few studies quantified the premature occurrence of these diseases in asbestos-exposed workers. Focus on premature disease onset (rate advancement or acceleration) can be useful in risk communication and for the evaluation of exposure impact. We estimated rate advancement for total mortality, lung cancer and pleural mesothelioma deaths, by classes of cumulative asbestos exposure in a pooled cohort of asbestos cement (AC) workers in Italy.

METHOD: The cohort study included 12 578 workers from 21 cohorts, with 6626 deaths in total, 858 deaths from lung cancer and 394 from pleural malignant neoplasm (MN). Rate advancement was estimated by fitting a competitive mortality Weibull model to the hazard of death over time since first exposure (TSFE).

RESULT: Acceleration time (AT) was estimated at different TSFE values. The highest level of cumulative exposure compared with the lowest, for pleural MN AT was 16.9 (95% CI 14.9 to 19.2) and 33.8 (95% CI 29.8 to 38.4) years at TSFE of 20 and 40 years, respectively. For lung cancer, it was 13.3 (95% CI 12.0 to 14.7) and 26.6 (95% CI 23.9 to 29.4) years, respectively. As for total mortality, AT was 3.35 (95% CI 2.98 to 3.71) years at 20 years TSFE, and 6.70 (95% CI 5.95 to 7.41) at 40 years TSFE.

CONCLUSION: The current study observed marked rate advancement after asbestos exposure for lung cancer and pleural mesothelioma, as well as for total mortality.}, } @article {pmid36355620, year = {2022}, author = {Kadariya, Y and Sementino, E and Shrestha, U and Gorman, G and White, JM and Ross, EA and Clapper, ML and Neamati, N and Miller, MS and Testa, JR}, title = {Inflammation as a chemoprevention target in asbestos-induced malignant mesothelioma.}, journal = {Carcinogenesis}, volume = {43}, number = {12}, pages = {1137-1148}, pmid = {36355620}, issn = {1460-2180}, support = {P30 CA006927/CA/NCI NIH HHS/United States ; HHSN261201500032I/NH/NIH HHS/United States ; }, mesh = {Mice ; Animals ; *Mesothelioma, Malignant ; Interleukin-6/genetics ; Sulindac ; Interleukin 1 Receptor Antagonist Protein/adverse effects ; Cytokine Receptor gp130/metabolism ; *Asbestos/toxicity ; Carcinogenesis ; Inflammation/drug therapy/pathology ; Chemoprevention ; *Mesothelioma/chemically induced/prevention & control/genetics ; }, abstract = {Malignant mesothelioma (MM) is an incurable cancer of the serosal lining that is often caused by exposure to asbestos. Therefore, novel agents for the prevention and treatment of this disease are urgently needed. Asbestos induces the release of pro-inflammatory cytokines such as IL-1β and IL-6, which play a role in MM development. IL-6 is a component of the JAK-STAT3 pathway that contributes to inflammation-associated tumorigenesis. Glycoprotein 130 (gp130), the signal transducer of this signaling axis, is an attractive drug target because of its role in promoting neoplasia via the activation of downstream STAT3 signaling. The anticancer drug, SC144, inhibits the interaction of gp130 with the IL-6 receptor (IL6R), effectively blunting signaling from this inflammatory axis. To test whether the inflammation-related release of IL-6 plays a role in the formation of MM, we evaluated the ability of SC144 to inhibit asbestos-induced carcinogenesis in a mouse model. The ability of sulindac and anakinra, an IL6R antagonist/positive control, to inhibit MM formation in this model was tested in parallel. Asbestos-exposed Nf2+/-;Cdkn2a+/- mice treated with SC144, sulindac or anakinra showed significantly prolonged survival compared to asbestos-exposed vehicle-treated mice. STAT3 activity was markedly decreased in MM specimens from SC144-treated mice. Furthermore, SC144 inhibited STAT3 activation by IL-6 in cultured normal mesothelial cells, and in vitro treatment of MM cells with SC144 markedly decreased the expression of STAT3 target genes. The emerging availability of newer, more potent SC144 analogs showing improved pharmacokinetic properties holds promise for future trials, benefitting individuals at high risk of this disease.}, } @article {pmid36346299, year = {2022}, author = {Fassio, F and Bussa, M and Oddone, E and Ferraro, OE and Puci, MV and Morandi, A and Castaldo, F and Broi, M and Uberti, F and Villani, S and Montomoli, C and Monti, MC}, title = {Health status of petrochemical workers: a narrative review.}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {44}, number = {1}, pages = {51-58}, pmid = {36346299}, issn = {1592-7830}, mesh = {Male ; Humans ; *Petroleum/toxicity ; *Mesothelioma ; *Occupational Exposure/adverse effects ; Health Status ; *Leukemia/complications ; *Occupational Diseases/epidemiology/etiology ; }, abstract = {Professional exposure to benzene has been extensively investigated by occupational medicine, leading to strict regulation of exposure threshold values. However, the petrochemical industry utilizes many chemical substances, whose exposure, without effective control and mitigation actions, could influence the health status over time. The aim of this narrative review is to describe health status of petrochemical workers related to occupational exposures, inquiring literature from 1980 to present. We used the PubMed and Web of Science search engines. As regards non-neoplastic diseases, despite heterogeneous prevalence estimates, we could say that standardized mortality rate (SMR) for hypertension, hypercholesterolemia and diabetes does not increase overall, compared to reference populations; a possible explanation may be the "healthy worker effect". Attention should be paid to color disperception and respiratory symptoms, due to toxic or irritating substances exposure. Studies concerning neoplastic pathology have mainly investigated mortality outcomes, finding no increase in cancer, except for melanoma or other skin cancers and leukemia. As regards the former, however, it is not excluded that other risk factors may contribute (e.g. UV rays in offshore workers), while for leukemia, only the most recent studies have analyzed various subtypes of hematopoietic tumors, highlighting a possible risk for the development of myelodysplastic syndrome. The risk of pleural mesothelioma was also increased, likely due to asbestos exposures, while the risk of death from prostate cancer remains controversial.}, } @article {pmid36325490, year = {2022}, author = {Ge, T and Phung, AL and Jhala, G and Trivedi, P and Principe, N and De George, DJ and Pappas, EG and Litwak, S and Sanz-Villanueva, L and Catterall, T and Fynch, S and Boon, L and Kay, TW and Chee, J and Krishnamurthy, B and Thomas, HE}, title = {Diabetes induced by checkpoint inhibition in nonobese diabetic mice can be prevented or reversed by a JAK1/JAK2 inhibitor.}, journal = {Clinical & translational immunology}, volume = {11}, number = {11}, pages = {e1425}, pmid = {36325490}, issn = {2050-0068}, abstract = {OBJECTIVES: Immune checkpoint inhibitors have achieved clinical success in cancer treatment, but this treatment causes immune-related adverse events, including type 1 diabetes (T1D). Our aim was to test whether a JAK1/JAK2 inhibitor, effective at treating spontaneous autoimmune diabetes in nonobese diabetic (NOD) mice, can prevent diabetes secondary to PD-L1 blockade.

METHODS: Anti-PD-L1 antibody was injected into NOD mice to induce diabetes, and JAK1/JAK2 inhibitor LN3103801 was administered by oral gavage to prevent diabetes. Flow cytometry was used to study T cells and beta cells. Mesothelioma cells were inoculated into BALB/c mice to induce a transplantable tumour model.

RESULTS: Anti-PD-L1-induced diabetes was associated with increased immune cell infiltration in the islets and upregulated MHC class I on islet cells. Anti-PD-L1 administration significantly increased islet T cell proliferation and islet-specific CD8[+] T cell numbers in peripheral lymphoid organs. JAK1/JAK2 inhibitor treatment blocked IFNγ-mediated MHC class I upregulation on beta cells and T cell proliferation mediated by cytokines that use the common γ chain receptor. As a result, anti-PD-L1-induced diabetes was prevented by JAK1/JAK2 inhibitor administered before or after checkpoint inhibitor therapy. Diabetes was also reversed when the JAK1/JAK2 inhibitor was administered after the onset of anti-PD-L1-induced hyperglycaemia. Furthermore, JAK1/JAK2 inhibitor intervention after checkpoint inhibitors did not reverse or abrogate the antitumour effects in a transplantable tumour model.

CONCLUSION: A JAK1/JAK2 inhibitor can prevent and reverse anti-PD-L1-induced diabetes by blocking IFNγ and γc cytokine activities. Our study provides preclinical validation of JAK1/JAK2 inhibitor use in checkpoint inhibitor-induced diabetes.}, } @article {pmid36318367, year = {2022}, author = {Caporali, S and Butera, A and Amelio, I}, title = {BAP1 in cancer: epigenetic stability and genome integrity.}, journal = {Discover oncology}, volume = {13}, number = {1}, pages = {117}, pmid = {36318367}, issn = {2730-6011}, abstract = {Mutations in BAP1 have been identified in a hereditary cancer predisposition syndrome and in sporadic tumours. Individuals carrying familiar BAP1 monoallelic mutations display hypersusceptibility to exposure-associated cancers, such as asbestos-driven mesothelioma, thus BAP1 status has been postulated to participate in gene-environment interaction. Intriguingly, BAP1 functions display also a high degree of tissue dependency, associated to a peculiar cancer spectrum and cell types of specific functions. Mechanistically, BAP1 functions as an ubiquitin carboxy-terminal hydrolase (UCH) and controls regulatory ubiquitination of histones as well as degradative ubiquitination of a range of protein substrates. In this article we provide an overview of the most relevant findings on BAP1, underpinning its tissue specific tumour suppressor function. We also discuss the importance of its epigenetic role versus the control of protein stability in the regulation of genomic integrity.}, } @article {pmid36305648, year = {2023}, author = {Allione, A and Viberti, C and Cotellessa, I and Catalano, C and Casalone, E and Cugliari, G and Russo, A and Guarrera, S and Mirabelli, D and Sacerdote, C and Gentile, M and Eichelmann, F and Schulze, MB and Harlid, S and Eriksen, AK and Tjønneland, A and Andersson, M and Dollé, MET and Van Puyvelde, H and Weiderpass, E and Rodriguez-Barranco, M and Agudo, A and Heath, AK and Chirlaque, MD and Truong, T and Dragic, D and Severi, G and Sieri, S and Sandanger, TM and Ardanaz, E and Vineis, P and Matullo, G}, title = {Blood cell DNA methylation biomarkers in preclinical malignant pleural mesothelioma: The EPIC prospective cohort.}, journal = {International journal of cancer}, volume = {152}, number = {4}, pages = {725-737}, doi = {10.1002/ijc.34339}, pmid = {36305648}, issn = {1097-0215}, support = {1000143/MRC_/Medical Research Council/United Kingdom ; C8221/A29017/CRUK_/Cancer Research UK/United Kingdom ; MR/N003284/1/MRC_/Medical Research Council/United Kingdom ; MR/M012190/1/MRC_/Medical Research Council/United Kingdom ; G0401527/MRC_/Medical Research Council/United Kingdom ; G1000143/MRC_/Medical Research Council/United Kingdom ; 14136/CRUK_/Cancer Research UK/United Kingdom ; MR/S019669/1/MRC_/Medical Research Council/United Kingdom ; 001/WHO_/World Health Organization/International ; }, mesh = {Humans ; Child, Preschool ; *Mesothelioma, Malignant ; *Mesothelioma/diagnosis/genetics/pathology ; DNA Methylation ; Case-Control Studies ; Prospective Studies ; *Pleural Neoplasms/diagnosis/genetics/pathology ; Biomarkers, Tumor/metabolism ; *Asbestos/adverse effects ; Genetic Markers ; Blood Cells ; *Lung Neoplasms/diagnosis/genetics/pathology ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer mainly caused by asbestos exposure. Specific and sensitive noninvasive biomarkers may facilitate and enhance screening programs for the early detection of cancer. We investigated DNA methylation (DNAm) profiles in MPM prediagnostic blood samples in a case-control study nested in the European Prospective Investigation into Cancer and nutrition (EPIC) cohort, aiming to characterise DNAm biomarkers associated with MPM. From the EPIC cohort, we included samples from 135 participants who developed MPM during 20 years of follow-up and from 135 matched, cancer-free, controls. For the discovery phase we selected EPIC participants who developed MPM within 5 years from enrolment (n = 36) with matched controls. We identified nine differentially methylated CpGs, selected by 10-fold cross-validation and correlation analyses: cg25755428 (MRI1), cg20389709 (KLF11), cg23870316, cg13862711 (LHX6), cg06417478 (HOOK2), cg00667948, cg01879420 (AMD1), cg25317025 (RPL17) and cg06205333 (RAP1A). Receiver operating characteristic (ROC) analysis showed that the model including baseline characteristics (age, sex and PC1wbc) along with the nine MPM-related CpGs has a better predictive value for MPM occurrence than the baseline model alone, maintaining some performance also at more than 5 years before diagnosis (area under the curve [AUC] < 5 years = 0.89; AUC 5-10 years = 0.80; AUC >10 years = 0.75; baseline AUC range = 0.63-0.67). DNAm changes as noninvasive biomarkers in prediagnostic blood samples of MPM cases were investigated for the first time. Their application can improve the identification of asbestos-exposed individuals at higher MPM risk to possibly adopt more intensive monitoring for early disease identification.}, } @article {pmid36304150, year = {2022}, author = {Lam, SK and Yan, S and Lam, JS and Feng, Y and Khan, M and Chen, C and Ko, FC and Ho, JC}, title = {Disturbance of the Warburg effect by dichloroacetate and niclosamide suppresses the growth of different sub-types of malignant pleural mesothelioma in vitro and in vivo.}, journal = {Frontiers in pharmacology}, volume = {13}, number = {}, pages = {1020343}, pmid = {36304150}, issn = {1663-9812}, abstract = {Background: Inhalation of asbestos fibers is the most common cause of malignant pleural mesothelioma (MPM). In 2004, the United States Food and Drug Administration approved a combination of cisplatin with pemetrexed to treat unresectable MPM. Nonetheless novel treatment is urgently needed. The objective of this study is to report the combination effect of dichloroacetate (DCA) or niclosamide (Nic) Nic in MPM. Materials and methods: The effect of a combination of DCA and Nic was studied using a panel of MPM cell lines (H28, MSTO-211H, H226, H2052, and H2452). Cell viability was monitored by MTT assay. Glycolysis, oxidative phosphorylation, glucose, glycogen, pyruvate, lactate, citrate, succinate and ATP levels were determined by corresponding ELISA. Apoptosis, mitochondrial transmembrane potential, cell cycle analysis, hydrogen peroxide and superoxide were investigated by flow cytometry. Cell migration and colony formation were investigated by transwell migration and colony formation assays respectively. The in vivo effect was confirmed using 211H and H226 nude mice xenograft models. Results and conclusion: Cell viability was reduced. Disturbance of glycolysis and/or oxidative phosphorylation resulted in downregulation of glycogen, citrate and succinate. DCA and/or Nic increased apoptosis, mitochondrial transmembrane depolarization, G2/M arrest and reactive oxygen species. Moreover, DCA and/or Nic suppressed cell migration and colony formation. Furthermore, a better initial tumor suppressive effect was induced by the DCA/Nic combination compared with either drug alone in both 211H and H226 xenograft models. In H226 xenografts, DCA/Nic increased median survival of mice compared with single treatment. Single drug and/or a combination disturbed the Warburg effect and activated apoptosis, and inhibition of migration and proliferation in vivo. In conclusion, dichloroacetate and/or niclosamide showed a tumor suppressive effect in MPM in vitro and in vivo, partially mediated by disturbance of glycolysis/oxidative phosphorylation, apoptosis, ROS production, G2/M arrest, and suppression of migration and proliferation.}, } @article {pmid36293328, year = {2022}, author = {Chernova, T and Grosso, S and Sun, XM and Tenor, AR and Cabeza, JZ and Craxton, A and Self, EL and Nakas, A and Cain, K and MacFarlane, M and Willis, AE}, title = {Extracellular Vesicles Isolated from Malignant Mesothelioma Cancer-Associated Fibroblasts Induce Pro-Oncogenic Changes in Healthy Mesothelial Cells.}, journal = {International journal of molecular sciences}, volume = {23}, number = {20}, pages = {}, pmid = {36293328}, issn = {1422-0067}, support = {29372/CRUK_/Cancer Research UK/United Kingdom ; MC_UU_00025/4/MRC_/Medical Research Council/United Kingdom ; MC_UU_00025/5/MRC_/Medical Research Council/United Kingdom ; MC_UU_00025/5 (RG94521)/MRC_/Medical Research Council/United Kingdom ; MC_UU_00025/7/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *Mesothelioma, Malignant ; *Cancer-Associated Fibroblasts/metabolism ; YAP-Signaling Proteins ; Cell Line, Tumor ; *Mesothelioma/pathology ; *Extracellular Vesicles/metabolism ; Carcinogenesis/metabolism ; Simvastatin ; Tumor Microenvironment ; }, abstract = {Malignant mesothelioma is an aggressive tumour of the pleura (MPM) or peritoneum with a clinical presentation at an advanced stage of the disease. Current therapies only marginally improve survival and there is an urgent need to identify new treatments. Carcinoma-associated fibroblasts (CAFs) represent the main component of a vast stroma within MPM and play an important role in the tumour microenvironment. The influence of CAFs on cancer progression, aggressiveness and metastasis is well understood; however, the role of CAF-derived extracellular vesicles (CAF-EVs) in the promotion of tumour development and invasiveness is underexplored. We purified CAF-EVs from MPM-associated cells and healthy dermal human fibroblasts and examined their effect on cell proliferation and motility. The data show that exposure of healthy mesothelial cells to EVs derived from CAFs, but not from normal dermal human fibroblasts (NDHF) resulted in activating pro-oncogenic signalling pathways and increased proliferation and motility. Consistent with its role in suppressing Yes-Associated Protein (YAP) activation (which in MPM is a result of Hippo pathway inactivation), treatment with Simvastatin ameliorated the pro-oncogenic effects instigated by CAF-EVs by mechanisms involving both a reduction in EV number and changes in EV cargo. Collectively, these data determine the significance of CAF-derived EVs in mesothelioma development and progression and suggest new targets in cancer therapy.}, } @article {pmid36282034, year = {2022}, author = {Mangone, L and Storchi, C and Pinto, C and Giorgi Rossi, P and Bisceglia, I and Romanelli, A}, title = {Incidence of malignant mesothelioma and asbestos exposure in the Emilia-Romagna region, Italy.}, journal = {La Medicina del lavoro}, volume = {113}, number = {5}, pages = {e2022047}, pmid = {36282034}, issn = {0025-7818}, mesh = {Female ; Humans ; Male ; Middle Aged ; *Asbestos/adverse effects ; Incidence ; Italy/epidemiology ; *Mesothelioma/epidemiology/etiology ; *Mesothelioma, Malignant ; *Occupational Exposure/adverse effects ; *Pleural Neoplasms/epidemiology/etiology ; }, abstract = {BACKGROUND: The aim of this study is to describe the incidence of malignant mesothelioma (MM) and asbestos exposure in an Italian region in the period 1996-June 2021.

METHODS: The study included cases with microscopic confirmation and those with instrumental confirmation. For each case, information on sex, age, tumour site, morphology and date of diagnosis was collected, along with details of exposure to asbestos.

RESULTS: 3,097 cases of MM (2,233 males and 864 females) were registered: 90.8% with microscopic confirmation. A total of 2,840 cases involved the pleura (92%), 230 cases the peritoneum (7%), and a small number of cases the pericardium and testis (9 and 18, respectively). Most cases (78.0%) occurred after 65 years of age, while only 1.5% concerned individuals with age < 45 years. The standardized incidence rate for the entire period (adjusted to the 2000 Italian standard population and calculated per 100,000 person-years) was equal to 3.9 in males and 1.4 in females, and the trend showed an increase with age in both sexes. Concerning asbestos exposure, 79.7% of cases were exposed (86.7% males and 60.1% females). In 70.3%, exposure was occupational (83.4% males and 33.2% females), while 20.7% of females and 0.8% of males had familial exposure. Building construction, rolling stock manufacture/repair and metalworking were the most prevalent economic activities associated with occupational exposure.

CONCLUSIONS: This study offers an overview of MM in an Italian region characterized by high incidence and high exposure due to its particular production activities.}, } @article {pmid36275913, year = {2022}, author = {Quigley, N and Lang-Lazdunski, L and Boily-Daoust, C and Couture, C and Fortin, M}, title = {An unusual isolated anterior mediastinal lesion.}, journal = {Respirology case reports}, volume = {10}, number = {11}, pages = {e01059}, pmid = {36275913}, issn = {2051-3380}, abstract = {Malignant pleural mesothelioma (MPM) is an infrequent tumour of poor prognosis with a strong association with asbestos exposure. Pleural effusion or thickening is the most common radiological finding. Thoracoscopic biopsy is the diagnostic modality of choice. In our report, we present the case of a career welder who consulted with vocal cord palsy and an atypical anterior mediastinal lesion. An EBUS-TBNA-guided biopsy and a thorough cytological assessment led to an unexpected diagnosis of epithelioid MPM. A localized anterior mediastinal lesion is an extremely infrequent presentation of MPM that deserves clinical recognition.}, } @article {pmid36240245, year = {2022}, author = {Jiménez-Ramírez, C and Gilbert Weber, D and Aguilar-Madrid, G and Brik, A and Juárez-Pérez, CA and Casjens, S and Raiko, I and Brüning, T and Johnen, G and Cabello-López, A}, title = {Assessment of miR-103a-3p in leukocytes-No diagnostic benefit in combination with the blood-based biomarkers mesothelin and calretinin for malignant pleural mesothelioma diagnosis.}, journal = {PloS one}, volume = {17}, number = {10}, pages = {e0275936}, pmid = {36240245}, issn = {1932-6203}, mesh = {*Asbestos/adverse effects ; Bilirubin ; Biomarkers, Tumor/genetics ; Calbindin 2/genetics ; Creatinine ; Female ; GPI-Linked Proteins/genetics ; Glucose ; Humans ; Leukocytes/pathology ; *Lung Neoplasms/pathology ; Male ; Mesothelin ; *Mesothelioma/diagnosis/genetics ; *Mesothelioma, Malignant ; *MicroRNAs/genetics ; Middle Aged ; *Pleural Neoplasms/pathology ; }, abstract = {Malignant pleural mesothelioma (MPM) is a cancer associated with asbestos exposure and its diagnosis is challenging due to the moderate sensitivities of the available methods. In this regard, miR-103a-3p was considered to increase the sensitivity of established biomarkers to detect MPM. Its behavior and diagnostic value in the Mexican population has not been previously evaluated. In 108 confirmed MPM cases and 218 controls, almost all formerly exposed to asbestos, we quantified miR-103-3a-3p levels in leukocytes using quantitative Real-Time PCR, together with mesothelin and calretinin measured in plasma by ELISA. Sensitivity and specificity of miR-103-3a-3p alone and in combination with mesothelin and calretinin were determined. Bivariate analysis was performed using Mann-Whitney U test and Spearman correlation. Non-conditional logistic regression models were used to calculate the area under curve (AUC), sensitivity, and specificity for the combination of biomarkers. Mesothelin and calretinin levels were higher among cases, remaining as well among males and participants ≤60 years old (only mesothelin). Significant differences for miR-103a-3p were observed between male cases and controls, whereas significant differences between cases and controls for mesothelin and calretinin were observed in men and women. At 95.5% specificity the individual sensitivity of miR-103a-3p was 4.4% in men, whereas the sensitivity of mesothelin and calretinin was 72.2% and 80.9%, respectively. Positive correlations for miR-103a-3p were observed with age, environmental asbestos exposure, years with diabetes mellitus, and glucose levels, while negative correlations were observed with years of occupational asbestos exposure, creatinine, erythrocytes, direct bilirubin, and leukocytes. The addition of miR-103a-3p to mesothelin and calretinin did not increase the diagnostic performance for MPM diagnosis. However, miR-103a-3p levels were correlated with several characteristics in the Mexican population.}, } @article {pmid36232554, year = {2022}, author = {Gesmundo, I and Pedrolli, F and Vitale, N and Bertoldo, A and Orlando, G and Banfi, D and Granato, G and Kasarla, R and Balzola, F and Deaglio, S and Cai, R and Sha, W and Papotti, M and Ghigo, E and Schally, AV and Granata, R}, title = {Antagonist of Growth Hormone-Releasing Hormone Potentiates the Antitumor Effect of Pemetrexed and Cisplatin in Pleural Mesothelioma.}, journal = {International journal of molecular sciences}, volume = {23}, number = {19}, pages = {}, pmid = {36232554}, issn = {1422-0067}, support = {2017HRTZYA//Italian Ministry of Instruction and Research PRIN 2017/ ; 2017S55RXB_002//Italian Ministry of Instruction and Research PRIN 2017/ ; 2019-2022//Fondazione Buzzi Unicem/ ; }, mesh = {Cell Line, Tumor ; Cisplatin/pharmacology/therapeutic use ; Cyclin D1 ; Cyclooxygenase 2 ; Growth Hormone-Releasing Hormone ; *HMGB1 Protein ; Humans ; Insulin-Like Growth Factor I/therapeutic use ; Matrix Metalloproteinase 2 ; Matrix Metalloproteinase 9/genetics ; *Mesothelioma/drug therapy/pathology ; *Mesothelioma, Malignant ; NF-kappa B/metabolism ; Pemetrexed/pharmacology/therapeutic use ; *Pleural Neoplasms/drug therapy/pathology ; Vascular Endothelial Growth Factor A/metabolism ; }, abstract = {Pleural mesothelioma (PM) is an aggressive cancer with poor prognosis and no effective therapies, mainly caused by exposure to asbestos. Antagonists of growth hormone-releasing hormone (GHRH) display strong antitumor effects in many experimental cancers, including lung cancer and mesothelioma. Here, we aimed to determine whether GHRH antagonist MIA-690 potentiates the antitumor effect of cisplatin and pemetrexed in PM. In vitro, MIA-690, in combination with cisplatin and pemetrexed, synergistically reduced cell viability, restrained cell proliferation and enhanced apoptosis, compared with drugs alone. In vivo, the same combination resulted in a strong growth inhibition of MSTO-211H xenografts, decreased tumor cell proliferation and increased apoptosis. Mechanistically, MIA-690, particularly with chemotherapeutic drugs, inhibited proliferative and oncogenic pathways, such as MAPK ERK1/2 and cMyc, and downregulated cyclin D1 and B1 mRNAs. Inflammatory pathways such as NF-kB and STAT3 were also reduced, as well as oxidative, angiogenic and tumorigenic markers (iNOS, COX-2, MMP2, MMP9 and HMGB1) and growth factors (VEGF and IGF-1). Overall, these findings strongly suggest that GHRH antagonists of MIA class, such as MIA-690, could increase the efficacy of standard therapy in PM.}, } @article {pmid36230710, year = {2022}, author = {Johnson, B and Zhuang, L and Rath, EM and Yuen, ML and Cheng, NC and Shi, H and Kao, S and Reid, G and Cheng, YY}, title = {Exploring MicroRNA and Exosome Involvement in Malignant Pleural Mesothelioma Drug Response.}, journal = {Cancers}, volume = {14}, number = {19}, pages = {}, pmid = {36230710}, issn = {2072-6694}, support = {RSP-080-19/20//Tour de Cure/ ; }, abstract = {Malignant pleural mesothelioma (MPM) is a deadly thoracic malignancy and existing treatment options are limited. Chemotherapy remains the most widely used first-line treatment regimen for patients with unresectable MPM, but is hampered by drug resistance issues. The current study demonstrated a modest enhancement of MPM cell sensitivity to chemotherapy drug treatment following microRNA (miRNA) transfection in MPM cell lines, albeit not for all tested miRNAs. This effect was more pronounced for FAK (PND-1186) small molecule inhibitor treatment; consistent with previously published data. We previously established that MPM response to survivin (YM155) small molecule inhibitor treatment is unrelated to basal survivin expression. Here, we showed that MPM response to YM155 treatment is enhanced following miRNA transfection of YM155-resistant MPM cells. We determined that YM155-resistant MPM cells secrete a higher level of exosomes in comparison to YM155-sensitive MPM cells. Despite this, an exosome inhibitor (GW4896) did not enhance MPM cell sensitivity to YM155. Additionally, our study showed no evidence of a correlation between the mRNA expression of inhibitor of apoptosis (IAP) gene family members and MPM cell sensitivity to YM155. However, two drug transporter genes, ABCA6 and ABCA10, were upregulated in the MPM cell lines and correlated with poor sensitivity to YM155.}, } @article {pmid36221913, year = {2022}, author = {Hariharan, A and Qi, W and Rehrauer, H and Wu, L and Ronner, M and Wipplinger, M and Kresoja-Rakic, J and Sun, S and Oton-Gonzalez, L and Sculco, M and Serre-Beinier, V and Meiller, C and Blanquart, C and Fonteneau, JF and Vrugt, B and Rüschoff, JH and Opitz, I and Jean, D and de Perrot, M and Felley-Bosco, E}, title = {Heterogeneous RNA editing and influence of ADAR2 on mesothelioma chemoresistance and the tumor microenvironment.}, journal = {Molecular oncology}, volume = {16}, number = {22}, pages = {3949-3974}, pmid = {36221913}, issn = {1878-0261}, mesh = {Animals ; Mice ; RNA Editing/genetics ; Tumor Microenvironment/genetics ; Drug Resistance, Neoplasm/genetics ; RNA-Binding Proteins/genetics/metabolism ; Adenosine Deaminase/genetics/metabolism ; *Mesothelioma, Malignant ; *Mesothelioma/genetics ; }, abstract = {We previously observed increased levels of adenosine-deaminase-acting-on-dsRNA (Adar)-dependent RNA editing during mesothelioma development in mice exposed to asbestos. The aim of this study was to characterize and assess the role of ADAR-dependent RNA editing in mesothelioma. We found that tumors and mesothelioma primary cultures have higher ADAR-mediated RNA editing compared to mesothelial cells. Unsupervised clustering of editing in different genomic regions revealed heterogeneity between tumor samples as well as mesothelioma primary cultures. ADAR2 expression levels are higher in BRCA1-associated protein 1 wild-type tumors, with corresponding changes in RNA editing in transcripts and 3'UTR. ADAR2 knockdown and rescue models indicated a role in cell proliferation, altered cell cycle, increased sensitivity to antifolate treatment, and type-1 interferon signaling upregulation, leading to changes in the microenvironment in vivo. Our data indicate that RNA editing contributes to mesothelioma heterogeneity and highlights an important role of ADAR2 not only in growth regulation in mesothelioma but also in chemotherapy response, in addition to regulating inflammatory response downstream of sensing nucleic acid structures.}, } @article {pmid36209608, year = {2023}, author = {Gualtieri, AF}, title = {Journey to the centre of the lung. The perspective of a mineralogist on the carcinogenic effects of mineral fibres in the lungs.}, journal = {Journal of hazardous materials}, volume = {442}, number = {}, pages = {130077}, doi = {10.1016/j.jhazmat.2022.130077}, pmid = {36209608}, issn = {1873-3336}, mesh = {Humans ; Mineral Fibers/toxicity ; Asbestos, Crocidolite ; Asbestos, Serpentine ; *Zeolites/chemistry ; Asbestos, Amphibole/toxicity ; Lung ; *Lung Neoplasms/chemically induced ; *Asbestos/toxicity ; }, abstract = {This work reviews the bio-chemical mechanisms leading to adverse effects produced when mineral fibres are inhaled and transported in the lungs from the perspective of a mineralogist. The behaviour of three known carcinogenic mineral fibres (crocidolite, chrysotile, and fibrous-asbestiform erionite) during their journey through the upper respiratory tract, the deep respiratory tract and the pleural cavity is discussed. These three fibres have been selected as they are the most socially and economically relevant mineral fibres representative of the classes of chain silicates (amphiboles), layer silicates (serpentine), and framework silicates (zeolites), respectively. Comparison of the behaviour of these fibres is made according to their specific crystal-chemical assemblages and properties. Known biological and subsequent pathologic effects which lead and contribute to carcinogenesis are critically reviewed under the mineralogical perspective and in relation to recent progress in this multidisciplinary field of research. Special attention is given to the understanding of the cause-effect relationships for lung cancer and malignant mesothelioma. Comparison with interstitial pulmonary fibrosis, or "asbestosis", will also be made here. This overview highlights open issues, data gaps, and conflicts in the literature for these topics, especially as regards relative potencies of the three mineral fibres under consideration for lung cancer and mesothelioma. Finally, an attempt is made to identify future research lines suitable for a general comprehensive model of the carcinogenicity of mineral fibres.}, } @article {pmid36187519, year = {2022}, author = {Kazi, M and Vispute, T and Shah, P and Ramadwar, M and Bhandare, MS and Shrikhande, SV and Chaudhari, VA}, title = {Localized gastric mesothelioma with nodal metastasis-an exceptionally rare entity.}, journal = {Indian journal of surgical oncology}, volume = {13}, number = {3}, pages = {612-615}, pmid = {36187519}, issn = {0975-7651}, abstract = {Localized mesothelioma is a rare disease with very few reports of presentation in visceral organs. We report a case of localized gastric mesothelioma with lymph node metastasis in a 32-year-old man without asbestos exposure. A failed attempt at resection was made before presentation at another center. He was given perioperative chemotherapy that was followed by a D2 radical subtotal gastrectomy and hyperthermic intraperitoneal chemotherapy. Histopathology showed epithelioid mesothelioma with nodal metastasis but without visceral peritoneal involvement. Cytoreductive surgery and regional chemotherapy are standard in diffuse mesothelioma. Management of localized mesothelioma is anecdotal; however aggressive surgery plays a central role with selective use of perioperative chemotherapy.}, } @article {pmid36181042, year = {2022}, author = {Cimen, F and Agackiran, Y and Düzgün, S and Aloglu, M and Senturk, A and Atikcan, S}, title = {Factors affecting the life expectancy in malignant pleural mesothelioma: Our 10 years of studies and experience.}, journal = {Medicine}, volume = {101}, number = {39}, pages = {e30711}, pmid = {36181042}, issn = {1536-5964}, mesh = {Female ; Fluorodeoxyglucose F18 ; Humans ; Life Expectancy ; *Lung Neoplasms/pathology ; Male ; *Mesothelioma/diagnosis ; *Mesothelioma, Malignant ; *Pleural Diseases ; *Pleural Neoplasms/pathology ; Positron Emission Tomography Computed Tomography/methods ; Prognosis ; Radiopharmaceuticals ; Retrospective Studies ; Tomography, X-Ray Computed ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive tumor with a poor prognosis. In our study, we aimed to investigate the specific clinical, laboratory, and radiological features of the tumor and the prognostic effect of SUVmax (maximum standardized uptake values) according to PET/CT (positron emission tomography). Demographic, therapeutic, clinical, and survival information of patients diagnosed with histologically-validated pleural mesothelioma in our hospital between January 2010 to December 2019 will be retrospectively scanned from the hospital records. A total of 116 patients, 61 men (52.6%), and 55 women (47.4%), were analyzed. Thirty five patients (30.2%) were over the age of 65. Percentage of patients over 65 years of age, neutrophil count, and PET SUV Max values, asbestos exposure and pleural thickening rate were significantly higher in the deceased patients' group than in the living patients' group (P = .042, P = .039, P = .002, P = .004, P = .037). T stage (tumor stage), N stage (lymph nodes stage), metastasis stage, and Grade distribution were significantly higher in the deceased patients' group than in the living patients' group (P < .000, P < .000, P = .003, P < .000). The rates of chemotherapy and surgical treatment, right lung location, and epithelioid pathology were significantly lower in the deceased patients' group compared to the living patients' group (P = .016, P = .030, P = .018, P = .008). The mean follow-up time was 13 months. Key determinants of survival in MPM include age, male gender, neutrophil increase, pleural thickening, high PET SUV max values, stage, histological type, asbestos exposure, and treatment regimen.}, } @article {pmid36174024, year = {2022}, author = {Wang, X and Katz, S and Miura, J and Karakousis, G and Roshkovan, L and Walker, S and McNulty, S and Ciunci, C and Cengel, K and Langer, CJ and Marmarelis, ME}, title = {A single-center retrospective cohort study of perioperative systemic chemotherapy in diffuse malignant peritoneal mesothelioma.}, journal = {PloS one}, volume = {17}, number = {9}, pages = {e0275187}, pmid = {36174024}, issn = {1932-6203}, mesh = {Adjuvants, Immunologic ; Adjuvants, Pharmaceutic ; Humans ; *Mesothelioma, Malignant ; Middle Aged ; *Peritoneal Neoplasms/drug therapy/surgery ; Peritoneum ; Platinum ; Retrospective Studies ; }, abstract = {BACKGROUND: Diffuse malignant peritoneal mesothelioma (DMPM) is a rare variant of malignant mesothelioma, representing 10-15% of malignant mesothelioma cases. The preferred therapeutic approach is cytoreductive surgery (CRS) accompanied by hyperthermic intraperitoneal chemotherapy (HIPEC); the role of systemic chemotherapy is not well established. While some limited retrospective studies report worse outcomes with neoadjuvant chemotherapy, our institution has favored the use of neoadjuvant chemotherapy for symptom relief and surgical optimization. The aim of our study was to assess the outcomes of patients receiving neoadjuvant chemotherapy, compared to those receiving adjuvant or no perioperative chemotherapy.

PATIENTS AND METHODS: We conducted a single-center retrospective cohort study of treatment-naïve, non-papillary DMPM patients seen at our institution between 1/1/2009 and 9/1/2019. We explored the effect of type of systemic therapy on clinical outcomes and estimated median overall survival (mOS) using Kaplan-Meier curves. Hazard ratios (HR) calculated by Cox proportional hazard model were used to estimate effect of the exposures on overall survival.

RESULTS: 47 patients were identified with DMPM (median age at diagnosis 61.2 years, 76.6% epithelioid histology, 74.5% white race, 55.3% known asbestos exposure). CRS was performed in 53.2% of patients (25/47); 76.0% of surgical patients received HIPEC (19/25). The majority received systemic chemotherapy (37/47, 78.7%); among patients receiving both CRS and chemotherapy, neoadjuvant chemotherapy was more common than adjuvant chemotherapy (12 neoadjuvant, 8 adjuvant). Overall mOS was 84.1 months. Among neoadjuvant patients, 10/12 underwent surgery, and 2 were lost to follow-up; the majority (9/10) had clinically stable or improved disease during the pre-operative period. There were numerical more issues with chemotherapy with the adjuvant patients (4/8: 2 switches in platinum agent, 2 patients stopped therapy) than with the neoadjuvant patients (2/10: 1 switch in platinum agent, 1 delay due to peri-procedural symptoms). Neoadjuvant chemotherapy was not associated with worse mOS compared to adjuvant chemotherapy (mOS NR vs 95.1 mo, HR 0.89, 95% CI 0.18-4.5, p = 0.89).

CONCLUSIONS: When used preferentially, the use of neoadjuvant chemotherapy in DMPM patients was not associated with worse outcomes compared to adjuvant chemotherapy. It was well-tolerated and did not prevent surgical intervention.}, } @article {pmid36165817, year = {2022}, author = {Han, Y and Zhang, T and Chen, H and Yang, X}, title = {Global magnitude and temporal trend of mesothelioma burden along with the contribution of occupational asbestos exposure in 204 countries and territories from 1990 to 2019: Results from the Global Burden of Disease Study 2019.}, journal = {Critical reviews in oncology/hematology}, volume = {179}, number = {}, pages = {103821}, doi = {10.1016/j.critrevonc.2022.103821}, pmid = {36165817}, issn = {1879-0461}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Asbestos/adverse effects ; Global Burden of Disease ; Global Health ; Humans ; *Mesothelioma/epidemiology/etiology ; *Mesothelioma, Malignant ; Quality-Adjusted Life Years ; Risk Factors ; }, abstract = {Understanding the burden of mesothelioma with the contribution of occupational asbestos exposure globally provides essential foundations for cancer control, policy decisions and resource allocation. Globally, 34,511 incident cases, 29,251 deaths and 668,104 disability-adjusted life years (DALYs) of mesothelioma were estimated in 2019. The age-standardized rates of incidence, mortality and DALYs all showed a slightly declining trend over the past 30 years, but the latest absolute number of mesothelioma burden almost doubled since 1990. The burden rate decreased among the population aged under 70 years, but increased among the population aged over 80 years, especially in the High socio-demographic index (SDI) region. The burden rate of mesothelioma attributable to asbestos exposure was positively associated with SDI at the national level. This study depicted a continuous increase in mesothelioma burden globally over the past 30 years. Controlling occupational asbestos exposure will reduce the mesothelioma burden, especially for higher SDI regions.}, } @article {pmid36161345, year = {2022}, author = {Golka, K and Böthig, R and Weistenhöfer, W and Jungmann, OP and Bergmann, S and Zellner, M and Schöps, W}, title = {[Occupation-related cancer in urology-Current knowledge including environmental medical aspects].}, journal = {Urologie (Heidelberg, Germany)}, volume = {61}, number = {11}, pages = {1198-1207}, pmid = {36161345}, issn = {2731-7072}, mesh = {Male ; Humans ; Female ; *Trichloroethylene ; *Urology ; *Mesothelioma/etiology ; Occupations ; *Kidney Neoplasms/chemically induced ; }, abstract = {Occupation-related cancers are of considerable importance, which is not yet adequately recognized in the field of urology. The three numerically most significant entities are tumors of the urinary tract caused by carcinogenic aromatic amines or polycyclic aromatic hydrocarbons, renal cell cancer after high exposure to the solvent trichloroethylene, and mesotheliomas of the tunica vaginalis of the testis after exposure to asbestos; however, these can only be recognized as occupation-related if an occupational history regarding the hazard relevant to the organ bearing the tumor is documented from the beginning of employment, e.g. by a questionnaire. This is because the relevant exposures generally date back several decades. With the exception of high exposure to trichloroethylene, the substances mentioned can also environmentally trigger the same tumors. In the context of environmental risk factors, it is of considerable importance that smoking is now considered to be a trigger for some 50% of all bladder cancers in men and women; however, smoking cessation results in a reduction in smoking-related cancer risk of over 30% after only 3-4 years. Work and commuting accidents, which are considered occupational risks, can lead to urological sequelae. For example, increased tumors of the bladder can occur after spinal cord injury lasting longer than 10 years.}, } @article {pmid36156859, year = {2022}, author = {Algranti, E and Santana, VS and Campos, F and Salvi, L and Saito, CA and Cavalcante, F and Correa-Filho, HR}, title = {Analysis of Mortality from Asbestos-Related Diseases in Brazil Using Multiple Health Information Systems, 1996-2017.}, journal = {Safety and health at work}, volume = {13}, number = {3}, pages = {302-307}, pmid = {36156859}, issn = {2093-7911}, abstract = {BACKGROUND: In Brazil, asbestos was intensively used from the 1960s until its ban in 2017. Mesothelioma, asbestosis, and pleural plaques are typical asbestos-related diseases (ARD-T). To create an ARD-T national database, death records from 1996-2017 were retrieved from several health information systems (HIS).

METHODS: All national HIS containing coded diagnoses (ICD-10) and death information were obtained. Linkage was performed to create a single database of ARD-T death records, either as underlying or contributory causes, in adults aged 30 years and older.

RESULTS: A total of 3,057 ARD-T death records were found, 2,405 (76.4%) of which being malignant mesotheliomas (MM). Pleural MM (n = 1,006; 41.8%) and unspecified MM (n = 792; 32.9%) prevailed. Male to female MM ratio (M:F) was 1.4:1, and higher ratios were found for non-malignant ARD-T: 3.5:1 for asbestosis and 2.4:1 for pleural plaques. Male crude annual mesothelioma mortality (CMmm x1,000,000) was 0.98 in 1996 and 2.26 in 2017, a 131.1% increment, while for females it was 1.04 and 1.25, a 20.2% increase, correspondingly. The small number of deaths with asbestosis and pleural plaques records precluded conclusive interpretations.

CONCLUSIONS: Even with the linkage of several HIS, ARD-T in death records remained in low numbers. MM mortality in men was higher and showed a rapid increase and, along with non-malignant ARD-T, higher M:F ratios suggested a predominant pattern of work-related exposure. The monitoring of workplace and environmental asbestos exposure needs to be improved, as well as the workers surveillance, following the recent Brazilian ban.}, } @article {pmid36139575, year = {2022}, author = {Tedesco, J and Jaradeh, M and Vigneswaran, WT}, title = {Malignant Pleural Mesothelioma: Current Understanding of the Immune Microenvironment and Treatments of a Rare Disease.}, journal = {Cancers}, volume = {14}, number = {18}, pages = {}, pmid = {36139575}, issn = {2072-6694}, abstract = {Malignant pleural mesothelioma is a rare disease with an annual incidence of around 3000 cases a year in the United States. Most cases are caused by asbestos exposure, with a latency period of up to 40 years. Pleural mesothelioma is an aggressive disease process with overall survival of roughly 6-12 months after the time of diagnosis. It is divided into three subtypes: epithelioid, mixed type, and sarcomatoid type, with the epithelioid subtype having the best overall survival. Often, the treatment is multimodality with surgery, chemotherapy, and radiation. The survival benefit is improved but remains marginal. New treatment options involving targeted immune therapies appear to offer some promise. The tumor microenvironment is the ecosystem within the tumor that interacts and influences the host immune system. Understanding this complex interaction and how the host immune system is involved in the progression of the disease process is important to define and guide potential treatment options for this devastating and rare disease.}, } @article {pmid36109807, year = {2022}, author = {Hoang, NTD and Hassan, G and Suehiro, T and Mine, Y and Matsuki, T and Fujii, M}, title = {BMP and activin membrane-bound inhibitor regulate connective tissue growth factor controlling mesothelioma cell proliferation.}, journal = {BMC cancer}, volume = {22}, number = {1}, pages = {984}, pmid = {36109807}, issn = {1471-2407}, support = {16K15922//Japan Society for the Promotion of Science/ ; }, mesh = {Activins ; Animals ; Cell Proliferation/genetics ; *Connective Tissue Growth Factor/genetics ; Cyclin D3 ; Cyclin-Dependent Kinases ; Humans ; *Membrane Proteins/genetics ; *Mesothelioma, Malignant ; Mice ; }, abstract = {BACKGROUND: Malignant mesothelioma (MM) is an aggressive mesothelial cell cancer type linked mainly to asbestos inhalation. MM characterizes by rapid progression and resistance to standard therapeutic modalities such as surgery, chemotherapy, and radiotherapy. Our previous studies have suggested that tumor cell-derived connective tissue growth factor (CTGF) regulates the proliferation of MM cells as well as the tumor growth in mouse xenograft models.

METHODS: In this study, we knock downed the bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) and CTGF in MM cells and investigated the relationship between both and their impact on the cell cycle and cell proliferation.

RESULTS: The knockdown of CTGF or BAMBI reduced MM cell proliferation. In contrast to CTGF knockdown which decreased BAMBI, knockdown of BAMBI increased CTGF levels. Knockdown of either BAMBI or CTGF reduced expression of the cell cycle regulators; cyclin D3, cyclin-dependent kinase (CDK)2, and CDK4. Further, in silico analysis revealed that higher BAMBI expression was associated with shorter overall survival rates among MM patients.

CONCLUSIONS: Our findings suggest that BAMBI is regulated by CTGF promoting mesothelioma growth by driving cell cycle progression. Therefore, the crosstalk between BAMBI and CTGF may be an effective therapeutic target for MM treatment.}, } @article {pmid36091141, year = {2022}, author = {Shi, H and Rath, EM and Lin, RCY and Sarun, KH and Clarke, CJ and McCaughan, BC and Ke, H and Linton, A and Lee, K and Klebe, S and Maitz, J and Song, K and Wang, Y and Kao, S and Cheng, YY}, title = {3-Dimensional mesothelioma spheroids provide closer to natural pathophysiological tumor microenvironment for drug response studies.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {973576}, pmid = {36091141}, issn = {2234-943X}, abstract = {Traditional studies using cancer cell lines are often performed on a two-dimensional (2D) cell culture model with a low success rate of translating to Phase I or Phase II clinical studies. In comparison, with the advent of developments three-dimensional (3D) cell culture has been championed as the latest cellular model system that better mimics in vivo conditions and pathological conditions such as cancer. In comparison to biospecimens taken from in vivo tissue, the details of gene expression of 3D culture models are largely undefined, especially in mesothelioma - an aggressive cancer with very limited effective treatment options. In this study, we examined the veracity of the 3D mesothelioma cell culture model to study cell-to-cell interaction, gene expression and drug response from 3D cell culture, and compared them to 2D cell and tumor samples. We confirmed via SEM analysis that 3D cells grown using the spheroid methods expressed highly interconnected cell-to-cell junctions. The 3D spheroids were revealed to be an improved mini-tumor model as indicated by the TEM visualization of cell junctions and microvilli, features not seen in the 2D models. Growing 3D cell models using decellularized lung scaffold provided a platform for cell growth and infiltration for all cell types including primary cell lines. The most time-effective method was growing cells in spheroids using low-adhesive U-bottom plates. However, not every cell type grew into a 3D model using the the other methods of hanging drop or poly-HEMA. Cells grown in 3D showed more resistance to chemotherapeutic drugs, exhibiting reduced apoptosis. 3D cells stained with H&E showed cell-to-cell interactions and internal architecture that better represent that of in vivo patient tumors when compared to 2D cells. IHC staining revealed increased protein expression in 3D spheroids compared to 2D culture. Lastly, cells grown in 3D showed very different microRNA expression when compared to that of 2D counterparts. In conclusion, 3D cell models, regardless of which method is used. Showed a more realistic tumor microenvironment for architecture, gene expression and drug response, when compared to 2D cell models, and thus are superior preclinical cancer models.}, } @article {pmid36077838, year = {2022}, author = {Trassl, L and Stathopoulos, GT}, title = {KRAS Pathway Alterations in Malignant Pleural Mesothelioma: An Underestimated Player.}, journal = {Cancers}, volume = {14}, number = {17}, pages = {}, pmid = {36077838}, issn = {2072-6694}, support = {Translational Research Project to GTS and LT//German Center for Lung Research/ ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare, incurable cancer of the mesothelial cells lining the lungs and the chest wall that is mainly caused by asbestos inhalation. The molecular mechanisms of mesothelial carcinogenesis are still unclear despite comprehensive studies of the mutational landscape of MPM, and the most frequently mutated genes BAP1, NF2, CDKN2A, TP53, and TSC1 cannot cause MPM in mice in a standalone fashion. Although KRAS pathway alterations were sporadically detected in older studies employing targeted sequencing, they have been largely undetected by next generation sequencing. We recently identified KRAS mutations and copy number alterations in a significant proportion of MPM patients. Here, we review and analyze multiple human datasets and the published literature to show that, in addition to KRAS, multiple other genes of the KRAS pathway are perturbed in a significant proportion of patients with MPM.}, } @article {pmid36077664, year = {2022}, author = {Ranzato, E and Bonsignore, G and Martinotti, S}, title = {ER Stress Response and Induction of Apoptosis in Malignant Pleural Mesothelioma: The Achilles Heel Targeted by the Anticancer Ruthenium Drug BOLD-100.}, journal = {Cancers}, volume = {14}, number = {17}, pages = {}, pmid = {36077664}, issn = {2072-6694}, abstract = {Malignant mesothelioma is a rare cancer arising from the serosal surfaces of the body, mainly from the pleural layer. This cancer is strongly related to asbestos exposure and shows a very inauspicious prognosis, because there are scarce therapeutic options for this rare disease. Thus, there is an urgent need to develop novel therapeutic approaches to treat this form of cancer. To explore the biology of malignant pleural mesothelioma (MPM), we previously observed that MPM cell lines show high expression of the GRP78 protein, which is a chaperone protein and the master regulator of the unfolded protein response (UPR) that resides in the endoplasmic reticulum (ER). Based on our previous studies showing the importance of GRP78 in MPM, we observed that BOLD-100, a specific modulator of GRP78 and the UPR, shows cytotoxicity against MPM cells. Our studies demonstrated that BOLD-100 increases ROS production and Ca[2+] release from the ER, leading to ER stress activation and, ultimately, to cell death. Our in vitro data strongly suggest that BOLD-100 inhibits the growth of MPM cell lines, proposing the application as a single agent, or in combination with other standard-of-care drugs, to treat MPM.}, } @article {pmid36077483, year = {2022}, author = {Pietrofesa, RA and Chatterjee, S and Kadariya, Y and Testa, JR and Albelda, SM and Christofidou-Solomidou, M}, title = {Synthetic Secoisolariciresinol Diglucoside (LGM2605) Prevents Asbestos-Induced Inflammation and Genotoxic Cell Damage in Human Mesothelial Cells.}, journal = {International journal of molecular sciences}, volume = {23}, number = {17}, pages = {}, pmid = {36077483}, issn = {1422-0067}, support = {1P30 ES013508-02/NH/NIH HHS/United States ; Office of the Vice Provost for Research//University of Pennsylvania School of Medicine/ ; NIH-R03 CA180548/NH/NIH HHS/United States ; 3P42ES023720-04S2/NH/NIH HHS/United States ; P30 ES013508/ES/NIEHS NIH HHS/United States ; }, mesh = {*Asbestos/toxicity ; Butylene Glycols ; Cytokines ; DNA Damage ; Glucosides ; *HMGB1 Protein ; Humans ; Inflammasomes ; Inflammation/pathology/prevention & control ; Interleukin-18 ; Interleukin-6 ; Reactive Oxygen Species ; Tumor Necrosis Factor-alpha ; }, abstract = {Although alveolar macrophages play a critical role in malignant transformation of mesothelial cells following asbestos exposure, inflammatory and oxidative processes continue to occur in the mesothelial cells lining the pleura that may contribute to the carcinogenic process. Malignant transformation of mesothelial cells following asbestos exposure occurs over several decades; however, amelioration of DNA damage, inflammation, and cell injury may impede the carcinogenic process. We have shown in an in vitro model of asbestos-induced macrophage activation that synthetic secoisolariciresinol diglucoside (LGM2605), given preventively, reduced inflammatory cascades and oxidative/nitrosative cell damage. Therefore, it was hypothesized that LGM2605 could also be effective in reducing asbestos-induced activation and the damage of pleural mesothelial cells. LGM2605 treatment (50 µM) of huma n pleural mesothelial cells was initiated 4 h prior to exposure to asbestos (crocidolite, 20 µg/cm2). Supernatant and cells were evaluated at 0, 2, 4, and 8 h post asbestos exposure for reactive oxygen species (ROS) generation, DNA damage (oxidized guanine), inflammasome activation (caspase-1 activity) and associated pro-inflammatory cytokine release (IL-1β, IL-18, IL-6, TNFα, and HMGB1), and markers of oxidative stress (malondialdehyde (MDA) and 8-iso-prostaglandin F2a (8-iso-PGF2α). Asbestos induced a time-dependent ROS increase that was significantly (p < 0.0001) reduced (29.4%) by LGM2605 treatment. LGM2605 pretreatment also reduced levels of asbestos-induced DNA damage by 73.6% ± 1.0%. Although levels of inflammasome-activated cytokines, IL-1β and IL-18, reached 29.2 pg/mL ± 0.7 pg/mL and 43.9 pg/mL ± 0.8 pg/mL, respectively, LGM2605 treatment significantly (p < 0.0001) reduced cytokine levels comparable to baseline (non-asbestos exposed) values (3.8 pg/mL ± 0.2 pg/mL and 5.4 pg/mL ± 0.2 pg/mL, respectively). Furthermore, levels of IL-6 and TNFα in asbestos-exposed mesothelial cells were high (289.1 pg/mL ± 2.9 pg/mL and 511.3 pg/mL ± 10.2 pg/mL, respectively), while remaining undetectable with LGM2605 pretreatment. HMGB1 (a key inflammatory mediator and initiator of malignant transformation) release was reduced 75.3% ± 0.4% by LGM2605. Levels of MDA and 8-iso-PGF2α, markers of oxidative cell injury, were significantly (p < 0.001) reduced by 80.5% ± 0.1% and 76.6% ± 0.3%, respectively. LGM2605, given preventively, reduced ROS generation, DNA damage, and inflammasome-activated cytokine release and key inflammatory mediators implicated in asbestos-induced malignant transformation of normal mesothelial cells.}, } @article {pmid36054746, year = {2022}, author = {Mai, HL and Deshayes, S and Nguyen, TV and Dehame, V and Chéné, AL and Brouard, S and Blanquart, C}, title = {IL-7 is expressed in malignant mesothelioma and has a prognostic value.}, journal = {Molecular oncology}, volume = {16}, number = {20}, pages = {3606-3619}, pmid = {36054746}, issn = {1878-0261}, mesh = {Humans ; *Mesothelioma, Malignant ; *Mesothelioma/genetics/diagnosis ; *Pleural Neoplasms/genetics ; Interleukin-7 ; Prognosis ; *Asbestos ; *Lung Neoplasms/pathology ; Receptors, Interleukin-7 ; Biomarkers ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive cancer mainly related to asbestos exposure. Despite recent therapeutic advances, notably immunotherapies, the benefit remains limited and restricted to a small percentage of patients. Thus, a better understanding of the disease is needed to identify new therapeutic strategies. Recently, interleukin 7 receptor (IL-7R) has been described as being expressed by MPM cells and associated with poorer patient survival. Thus, the aim of this work was to study the IL-7R/IL-7 pathway in MPM using patient samples. We found that, although more than 40% of MPM cells expressed IL-7R, IL-7 had no effect on their intracellular signaling. Accordingly, the addition of IL-7 to the culture medium did not affect MPM cell growth. Using The Cancer Genome Atlas (TCGA) database, we showed that high IL7 gene expression in MPM tumors was associated with a higher overall patient survival and an induction of genes involved in the immune response. In pleural effusions (PEs), we found that IL-7 concentration was not a good diagnostic biomarker. However, we observed that high IL-7 levels in PEs were associated with shorter survival of MPM patients, but not of lung cancer patients. The prognostic value of IL-7 was also conserved when only patients with epithelioid mesothelioma, the most common histological type of MPM, were analyzed. Taken together, our study suggests that, although the IL-7R/IL-7 signaling pathway is not functional in MPM cells, IL-7 expression in PEs may have prognostic value in MPM patients.}, } @article {pmid36039621, year = {2022}, author = {Kenchetty, PK and Balasundaram, S and Rao, K}, title = {An uncommon aetiology for a common clinical problem: Primary pericardial mesothelioma.}, journal = {The National medical journal of India}, volume = {35}, number = {1}, pages = {14-16}, doi = {10.25259/NMJI_273_20}, pmid = {36039621}, issn = {2583-150X}, mesh = {*Asbestos ; *Heart Neoplasms/complications/diagnostic imaging ; Humans ; Male ; *Mesothelioma/etiology/pathology/therapy ; Middle Aged ; Pericardium/diagnostic imaging/pathology ; *Peritoneal Neoplasms ; }, abstract = {Mesothelioma is a tumour arising from the mesothelial cells lining the pleura, pericardium, peritoneum, or the tunica vaginalis of testes. Primary pericardial mesothelioma is a rare tumour that can have varied manifestations and survival in patients with malignant pericardial tumours is generally dismal. The role of asbestos in pericardial mesotheliomas is less well established compared to that in pleural or peritoneal mesotheliomas. The prognosis is generally poor with the treatment options available. We present a middle-aged man with large pericardial effusion secondary to primary pericardial mesothelioma with no previous exposure to asbestos.}, } @article {pmid36039211, year = {2022}, author = {Kerosky, ZP and Powell, CR and Lindholm, PC}, title = {Malignant Peritoneal Mesothelioma Presenting with High Protein, High Serum-Ascites Albumin Gradient.}, journal = {Cureus}, volume = {14}, number = {7}, pages = {e27286}, pmid = {36039211}, issn = {2168-8184}, abstract = {Mesothelioma is a difficult-to-detect neoplasm that rarely develops in the peritoneum. In patients with unexplained ascites, pleural fluid analysis and ultrasonography is often the first step to achieving a diagnosis. This case report shares a unique presentation in which a patient who presented with unexplained ascites, was initially thought to have cirrhosis but was later found to have malignant peritoneal mesothelioma after cross-sectional imaging and tissue acquisition. This case illustrates the importance of a high clinical index of suspicion for mesothelioma given its variety of clinical presentations, as well as the utility of early cross-sectional imaging in such cases.}, } @article {pmid36012262, year = {2022}, author = {Setlai, BP and Mkhize-Kwitshana, ZL and Mehrotra, R and Mulaudzi, TV and Dlamini, Z}, title = {Microbiomes, Epigenomics, Immune Response, and Splicing Signatures Interplay: Potential Use of Combination of Regulatory Pathways as Targets for Malignant Mesothelioma.}, journal = {International journal of molecular sciences}, volume = {23}, number = {16}, pages = {}, pmid = {36012262}, issn = {1422-0067}, mesh = {*Asbestos/adverse effects ; Epigenomics ; Humans ; Immunity ; *Lung Neoplasms/genetics ; *Mesothelioma/etiology ; *Mesothelioma, Malignant ; *Microbiota ; }, abstract = {Malignant mesotheliomas (MM) are hard to treat malignancies with poor prognosis and high mortality rates. This cancer is highly misdiagnosed in Sub-Saharan African countries. According to literature, the incidence of MM is likely to increase particularly in low-middle-income countries (LMICs). The burden of asbestos-induced diseases was estimated to be about 231,000 per annum. Lack of awareness and implementation of regulatory frameworks to control exposure to asbestos fibers contributes to the expected increase. Exposure to asbestos fibers can lead to cancer initiation by several mechanisms. Asbestos-induced epigenetic modifications of gene expression machinery and non-coding RNAs promote cancer initiation and progression. Furthermore, microbiome-epigenetic interactions control the innate and adaptive immunity causing exacerbation of cancer progression and therapeutic resistance. This review discusses epigenetic mechanisms with more focus on miRNAs and their interaction with the microbiome. The potential use of epigenetic alterations and microbiota as specific biomarkers to aid in the early detection and/or development of therapeutic targets is explored. The advancement of combinatorial therapies to prolong overall patient survival or possible eradication of MM especially if it is detected early is discussed.}, } @article {pmid36000688, year = {2022}, author = {Gregório, PHP and Terra, RM and Lima, LP and Pêgo-Fernandes, PM}, title = {Mesothelioma in a developing country: a retrospective analysis of the diagnostic process.}, journal = {Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia}, volume = {48}, number = {5}, pages = {e20220064}, pmid = {36000688}, issn = {1806-3756}, mesh = {*Asbestos/toxicity ; Developing Countries ; Humans ; *Lung Neoplasms/chemically induced/diagnosis/therapy ; *Mesothelioma/diagnosis/etiology/therapy ; *Mesothelioma, Malignant ; Middle Aged ; *Pleural Neoplasms/diagnosis/therapy ; Retrospective Studies ; }, abstract = {OBJECTIVE: To evaluate the process of diagnosing patients with malignant pleural mesothelioma (MPM) at a tertiary care hospital.

METHODS: This was a retrospective study involving patients referred to a tertiary-care cancer center in Brazil between 2009 and 2020. The diagnostic process was divided into four steps: onset of symptoms, referral to a specialist visit, histopathological diagnosis, and beginning of treatment. The intervals between each phase and the factors for delays were evaluated. Data including clinical status, radiological examinations, staging, treatment modalities, and survival outcomes were collected.

RESULTS: During the study period, 66 patients (mean age = 64 years) were diagnosed with MPM and underwent treatment. Only 27 (41%) of the patients had knowledge of prior exposure to asbestos. The median number of months (IQR) between the onset of symptoms and the first specialist visit, between the specialist visit and histopathological characterization, and between definite diagnosis and beginning of treatment was, respectively, 6.5 (2.0-11.4), 1.5 (0.6-2.1), and 1.7 (1.2-3.4). The knowledge of prior asbestos exposure was associated with a shorter time to referral to a specialist (median: 214 vs. 120 days; p = 0.04). A substantial number of nondiagnostic procedures and false-negative biopsy results (the majority of which involved the use of Cope needle biopsy) were found to be decisive factors for the length of waiting time. The mean overall survival was 11.9 months.

CONCLUSIONS: The unfamiliarity of health professionals with MPM and the patient's lack of knowledge of prior asbestos exposure were the major factors to cause a long time interval between the onset of symptoms and beginning of treatment. An overall survival shorter than 1 year is likely to have been due to the aforementioned delays.}, } @article {pmid35987988, year = {2022}, author = {Muti, P and Sacconi, A and Pulito, C and Orlandi, G and Donzelli, S and Morrone, A and Jiulian, J and Cox, GP and Kolb, M and Pond, G and Kavsak, P and Levine, MN and Blandino, G and Strano, S}, title = {Artichoke phytocomplex modulates serum microRNAs in patients exposed to asbestos: a first step of a phase II clinical trial.}, journal = {Journal of experimental & clinical cancer research : CR}, volume = {41}, number = {1}, pages = {255}, pmid = {35987988}, issn = {1756-9966}, mesh = {*Asbestos/toxicity ; Biomarkers, Tumor ; *Cynara scolymus ; GPI-Linked Proteins/genetics ; Humans ; *Lung Neoplasms/etiology ; Male ; Mesothelin ; *Mesothelioma/drug therapy/genetics ; *Mesothelioma, Malignant ; *MicroRNAs/genetics ; *Pleural Neoplasms/drug therapy/genetics ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma is a highly aggressive tumor associated with asbestos exposure. There are few effective treatment options for mesothelioma, and patients have a very poor prognosis. Mesothelioma has the potential to represent an appropriate disease to prevent because of its strong association with asbestos exposure and the long latency from exposure to the disease on-set.

METHODS: In the present study, we tested biological activity and toxicity of an artichoke freeze-dried extract (AWPC) as potential complementary preventive/early stage treatment agent for mesothelioma. This phase II clinical study then was conducted in 18 male-patients with evidence of radiographic characteristics related to asbestos exposure such as asbestosis or benign pleural disease as surrogate disease for mesothelioma clinical model.

RESULTS: We investigate AWPC biological activity assessing its effect on mesothelin serum level, a glycoprotein with low expression in normal mesothelial cells and high expression in mesothelioma and asbestos related diseases. We also assess the AWPC effect on circulating miRNAs, as novel biomarkers of both cancer risk and response to therapeutic targets. While we found a small and not significant effect of AWPC on mesothelin serum levels, we observed that AWPC intake modulated 11 serum miRNAs related to gene-pathways connected to mesothelioma etiology and development. In terms of toxicity, we also did not observe any severe adverse effects associated to AWPC treatment, only gastro-intestinal symptoms were reported by five study participants.

CONCLUSIONS: We observed an interesting AWPC effect on miRNAs which targets modulate mesothelioma development. New and much larger clinical studies based on follow-up of workers exposed to asbestos are needed to corroborate the role of AWPC in prevention and early treatment of mesothelioma.

TRIAL REGISTRATION: ClinicalTrials.gov, NCT02076672 . Registered 03/03/2014.}, } @article {pmid35978837, year = {2022}, author = {Jiang, Z and Chen, J and Chen, J and Feng, L and Jin, M and Zhong, H and Ju, L and Zhu, L and Xiao, Y and Jia, Z and Xu, C and Yu, D and Zhang, X and Lou, J}, title = {Mortality due to respiratory system disease and lung cancer among female workers exposed to chrysotile in Eastern China: A cross-sectional study.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {928839}, pmid = {35978837}, issn = {2234-943X}, abstract = {Female workers in the asbestos processing industry of Eastern China are at high risk of developing multiple types of cancer, and more data are urgently needed to better understand and address this issue. Death certificate data were selected from an asbestos processing city in China from 2005 to 2006. Information was investigated using the relatives of those individuals who had died as sources of information. Individuals were classified into one of three asbestos exposure levels. Standardized mortality ratio and 95% confidence interval were calculated. A total of 2,964 individual deaths were identified from 2005 to 2006; of these, 21.4% were occupationally exposed to asbestos. The main cause of death was circulatory system diseases (21.2%). The proportion of individuals with respiratory system diseases increased by age among each exposure subgroup (P trend < 0.01). Among females, a significant trend was observed between increased asbestos exposure and mortality due to respiratory system diseases and lung cancer. Our study indicated that asbestos exposure was associated with excess mortality from lung cancer and respiratory diseases, particularly among female workers in an asbestos processing area in Eastern China.}, } @article {pmid35941734, year = {2022}, author = {Silvestri, S and Ciapini, C and Innocenti, A}, title = {Past Asbestos Exposure in Rolling Stock Manufacturing in the Absence of Environmental Monitoring: An Original Method.}, journal = {Journal of occupational and environmental medicine}, volume = {64}, number = {10}, pages = {e635-e640}, doi = {10.1097/JOM.0000000000002656}, pmid = {35941734}, issn = {1536-5948}, mesh = {*Asbestos ; Cohort Studies ; Environmental Monitoring ; Humans ; *Mesothelioma ; *Occupational Diseases ; *Occupational Exposure/adverse effects/analysis ; }, abstract = {OBJECTIVE: The aim of this study is the reconstruction of asbestos exposure in absence of environmental monitoring data, to use the results in a cohort study of railway rolling stock workers.

METHODS: To reconstruct past exposures, the production data (number of rolling stock and asbestos content) and working methods were reconstructed with former employees and company documentation, literature data, and author expertise.

RESULTS: The result of the work is a job/exposure matrix from 1956 to 1979, when sprayed asbestos was used as insulator of the metal bodies. Annual exposure estimate varies from 0.08 to 4.9 fb/mL depending on the specific jobs. Thirty-one mesotheliomas with occupational exposure, one with environmental and one with family exposures, were identified.

CONCLUSIONS: The originality of the study consists on the use of company production data to establish frequency duration of asbestos exposure.}, } @article {pmid35940275, year = {2023}, author = {Chun, CP and Song, LX and Zhang, HP and Guo, DD and Xu, GX and Li, Y and Xin, X and Cao, J and Li, F}, title = {Malignant peritoneal mesothelioma.}, journal = {The American journal of the medical sciences}, volume = {365}, number = {1}, pages = {99-103}, doi = {10.1016/j.amjms.2022.07.008}, pmid = {35940275}, issn = {1538-2990}, mesh = {Male ; Humans ; Aged ; *Mesothelioma, Malignant/complications ; Ascites/diagnostic imaging/etiology ; *Mesothelioma/diagnosis/etiology/pathology ; *Asbestos/toxicity ; *Pleural Neoplasms/diagnosis ; *Peritoneal Neoplasms/diagnosis/etiology/pathology ; }, abstract = {Malignant peritoneal mesothelioma (MPM) is a rare, life-threatening malignant tumor. We present a report of a rare case of a 67-year-old male patient with MPM and severe abdominal pain, bloating, and bloody ascites as manifestations. The diagnosis was confirmed by cytology of ascites aspiration fluid and further verified by laparoscopic exploratory biopsy. The characteristics of signs and clinical manifestations in this case are less common. As everyone knows, asbestos exposure is usually associated with pleural mesothelioma, but only 6%-10% of malignant mesothelioma cases originate from the peritoneum, which is far less than pleural mesothelioma. Generally, its non-specificity provides a huge challenge to medical professionals in its diagnosis, and this is also the main reason for delayed diagnosis. Patients should be vigilant, even though no clear risk factor is observed.}, } @article {pmid35937383, year = {2022}, author = {Shobana, M and Balasraswathi, VR and Radhika, R and Oleiwi, AK and Chaudhury, S and Ladkat, AS and Naved, M and Rahmani, AW}, title = {Classification and Detection of Mesothelioma Cancer Using Feature Selection-Enabled Machine Learning Technique.}, journal = {BioMed research international}, volume = {2022}, number = {}, pages = {9900668}, pmid = {35937383}, issn = {2314-6141}, mesh = {Algorithms ; Bayes Theorem ; Humans ; *Machine Learning ; *Mesothelioma/classification/diagnosis ; Mesothelioma, Malignant/diagnosis ; Multiple Myeloma/diagnosis ; }, abstract = {Cancer of the mesothelium, sometimes referred to as malignant mesothelioma (MM), is an extremely uncommon form of the illness that almost always results in death. Chemotherapy, surgery, radiation therapy, and immunotherapy are all potential treatments for multiple myeloma; however, the majority of patients are identified with the disease at an advanced stage, at which time it is resistant to these therapies. After obtaining a diagnosis of advanced multiple myeloma, the average length of time that a person lives is one year after hearing this news. There is a substantial link between asbestos exposure and mesothelioma (MM). Using an approach that enables feature selection and machine learning, this article proposes a classification and detection method for mesothelioma cancer. The CFS correlation-based feature selection approach is first used in the feature selection process. It acts as a filter, selecting just the traits that are relevant to the categorization. The accuracy of the categorization model is improved as a direct consequence of this. After that, classification is carried out with the help of naive Bayes, fuzzy SVM, and the ID3 algorithm. Various metrics have been utilized during the process of measuring the effectiveness of machine learning strategies. It has been discovered that the choice of features has a substantial influence on the accuracy of the categorization.}, } @article {pmid35931425, year = {2022}, author = {Røe, OD and Creaney, J and , }, title = {Response to "Revisiting 'BAP1ness' in Malignant Pleural Mesothelioma".}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {17}, number = {8}, pages = {e69-e70}, doi = {10.1016/j.jtho.2022.05.013}, pmid = {35931425}, issn = {1556-1380}, mesh = {Humans ; *Lung Neoplasms/genetics/pathology ; *Mesothelioma/pathology ; *Mesothelioma, Malignant ; *Pleural Neoplasms/pathology ; }, } @article {pmid35931423, year = {2022}, author = {Yang, H and Gaudino, G and Bardelli, F and Carbone, M}, title = {Does the Amount of Asbestos Exposure Influence Prognosis?.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {17}, number = {8}, pages = {949-952}, doi = {10.1016/j.jtho.2022.06.003}, pmid = {35931423}, issn = {1556-1380}, mesh = {*Asbestos/adverse effects ; Humans ; *Lung Neoplasms/etiology ; *Mesothelioma/etiology ; *Occupational Exposure/adverse effects ; Prognosis ; }, } @article {pmid35911327, year = {2022}, author = {Tachibana, M and Nozawa, M and Kamimura, K and Tsutsumi, Y}, title = {Synchronous Jejunal Sarcomatoid Carcinoma and Incidentally Associated Localized Peritoneal Malignant Mesothelioma.}, journal = {Cureus}, volume = {14}, number = {6}, pages = {e26270}, pmid = {35911327}, issn = {2168-8184}, abstract = {Sarcomatoid carcinoma (SCA) of the small bowel is a rare aggressive variant of small intestinal cancer accompanying a poor prognosis. The tumor primarily affects middle-aged and elderly patients. We report herein a 67-year-old Japanese male who manifested anemia. He had a history of asbestos exposure 30 years earlier. An abdominal computed tomography (CT) scan showed a 6.5-cm aneurysmal, dilated mass of the small intestine. Capsule endoscopy revealed a large circumferential hemorrhagic ulcerative lesion in the jejunum. Biopsy indicated sarcomatoid carcinoma, and partial resection of the small bowel and adjacent transverse colon and omentum was performed. In addition to the T3N0M0 jejunal giant sarcomatoid carcinoma (SCA), a 3-mm small localized peritoneal (omental) malignant mesothelioma (LMM) was also incidentally included. Synchronous presentation of small intestinal and mesothelial malignancies is extremely rare, and the avoidance of incorrect clinical staging is critically important. Surgical resection is still considered the best first-line therapy, because of a poor response to chemotherapy and radiotherapy. Dual-color fluorescent in situ hybridization (FISH) for p16/CDKN2A and chromosome 9 indicated homologous deletion of p16/CDKN2A in SCA and a normal pattern in LMM. Methylthioadenosine phosphorylase (MTAP) was negative in SCA but positive in LMM. Both tumors consistently expressed BRCA1-associated protein 1 (BAP1). Tumor necrosis factor receptor-associated factor 7 (TRAF7) was suppressed, and neural cell adhesion molecule L1 precursor (NCAML1/L1CAM) was agitated in both tumors. Diffuse and strong expression of programmed death-ligand 1 (PD-L1) and the association of tumor-infiltrating lymphocytes in SCA may indicate a potential for PD-L1-targeted immunotherapy for treating this type of aggressive cancer. PD-L1 was focally expressed in LMM. The postoperative course was uneventful for two years.}, } @article {pmid35908620, year = {2022}, author = {Parvathaneni, V and Chilamakuri, R and Kulkarni, NS and Wang, X and Agarwal, S and Gupta, V}, title = {Repurposing clofazimine for malignant pleural mesothelioma treatment - In-vitro assessment of efficacy and mechanism of action.}, journal = {Life sciences}, volume = {306}, number = {}, pages = {120843}, doi = {10.1016/j.lfs.2022.120843}, pmid = {35908620}, issn = {1879-0631}, mesh = {*Antineoplastic Agents/pharmacology/therapeutic use ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Clofazimine/pharmacology/therapeutic use ; Drug Repositioning ; Humans ; *Lung Neoplasms/pathology ; *Mesothelioma/drug therapy/metabolism ; *Mesothelioma, Malignant ; *Pleural Neoplasms/drug therapy/metabolism/pathology ; beta Catenin ; }, abstract = {AIMS: Malignant pleural mesothelioma (MPM) is a rare cancer of lungs' pleural cavity, with minimally effective therapies available. Thus, there exists a necessity for drug repurposing which is an attractive strategy for drug development in MPM. Repurposing of an old FDA-approved anti-leprotic drug, Clofazimine (CFZ), presents an outstanding opportunity to explore its efficacy in treating MPM.

MAIN METHODS: Cytotoxicity, scratch assay, and clonogenic assays were employed to determine CFZ's ability to inhibit cell viability, cell migration, and colony growth. 3D Spheroid cell culture studies were performed to identify tumor growth inhibition potential of CFZ in MSTO-211H cell line. Gene expression analysis was performed using RT-qPCR assays to determine the CFZ's effect of key genes. Western blot studies were performed to determine CFZ's ability to induce apoptosis its effect to induce autophagy marker.

KEY FINDINGS: CFZ showed significant cytotoxicity against both immortalized and primary patient-derived cell lines with IC50 values ranging from 3.4 μM (MSTO-211H) to 7.1 μM (HAY). CFZ significantly impaired MPM cell cloning efficiency, migration, and tumor spheroid formation. 3D Spheroid model showed that CFZ resulted in reduction in spheroid volume. RT-qPCR data showed downregulation of genes β-catenin, BCL-9, and PRDX1; and upregulation of apoptosis markers such as PARP, Cleaved caspase 3, and AXIN2. Additionally, immunoblot analysis showed that CFZ down-regulates the expression of β-catenin (apoptosis induction) and up-regulates p62, LC3B protein II (autophagy inhibition).

SIGNIFICANCE: It can be concluded that CFZ could be a promising molecule to repurpose for MPM treatment which needs numerous efforts from further studies.}, } @article {pmid35906513, year = {2022}, author = {Dubois, F and Bazille, C and Levallet, J and Maille, E and Brosseau, S and Madelaine, J and Bergot, E and Zalcman, G and Levallet, G}, title = {Molecular Alterations in Malignant Pleural Mesothelioma: A Hope for Effective Treatment by Targeting YAP.}, journal = {Targeted oncology}, volume = {17}, number = {4}, pages = {407-431}, pmid = {35906513}, issn = {1776-260X}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; *Asbestos ; Bevacizumab/therapeutic use ; Humans ; *Lung Neoplasms/drug therapy ; *Mesothelioma/drug therapy/pathology ; *Mesothelioma, Malignant ; Pemetrexed/therapeutic use ; *Pleural Neoplasms/drug therapy/pathology ; }, abstract = {Malignant pleural mesothelioma is a rare and aggressive neoplasm, which has primarily been attributed to the exposure to asbestos fibers (83% of cases); yet, despite a ban of using asbestos in many countries, the incidence of malignant pleural mesothelioma failed to decline worldwide. While little progress has been made in malignant pleural mesothelioma diagnosis, bevacizumab at first, then followed by double immunotherapy (nivolumab plus ipilumumab), were all shown to improve survival in large phase III randomized trials. The morphological analysis of the histological subtyping remains the primary indicator for therapeutic decision making at an advanced disease stage, while a platinum-based chemotherapy regimen combined with pemetrexed, either with or without bevacizumab, is still the main treatment option. Consequently, malignant pleural mesothelioma still represents a significant health concern owing to poor median survival (12-18 months). Given this context, both diagnosis and therapy improvements require better knowledge of the molecular mechanisms underlying malignant pleural mesothelioma's carcinogenesis and progression. Hence, the Hippo pathway in malignant pleural mesothelioma initiation and progression has recently received increasing attention, as the aberrant expression of its core components may be closely related to patient prognosis. The purpose of this review was to provide a critical analysis of our current knowledge on these topics, the main focus being on the available evidence concerning the role of each Hippo pathway's member as a promising biomarker, enabling detection of the disease at earlier stages and thus improving prognosis.}, } @article {pmid35885614, year = {2022}, author = {Sculco, M and La Vecchia, M and Aspesi, A and Clavenna, MG and Salvo, M and Borgonovi, G and Pittaro, A and Witel, G and Napoli, F and Listì, A and Grosso, F and Libener, R and Maconi, A and Rena, O and Boldorini, R and Giachino, D and Bironzo, P and Maffè, A and Alì, G and Elefanti, L and Menin, C and Righi, L and Tampieri, C and Scagliotti, GV and Dianzani, C and Ferrante, D and Migliore, E and Magnani, C and Mirabelli, D and Matullo, G and Dianzani, I}, title = {Diagnostics of BAP1-Tumor Predisposition Syndrome by a Multitesting Approach: A Ten-Year-Long Experience.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {12}, number = {7}, pages = {}, pmid = {35885614}, issn = {2075-4418}, support = {21390//Italian Association for Cancer Research/ ; 23760//Italian Association for Cancer Research/ ; //This research was funded by the offer of compensation to the inhabitants of Casale Monferrato deceased or affected by mesothelioma - HERMES (HEreditary Risk in MESothelioma)/ ; //The APC was funded by the Italian Ministry of Education, University and Research (MIUR) program "Departments of Excellence 2018-2022", FOHN Project - Department of Health Sciences, Università del Piemonte Orientale/ ; }, abstract = {Germline mutations in the tumor suppressor gene BRCA1-associated protein-1 (BAP1) lead to BAP1 tumor predisposition syndrome (BAP1-TPDS), characterized by high susceptibility to several tumor types, chiefly melanoma, mesothelioma, renal cell carcinoma, and basal cell carcinoma. Here, we present the results of our ten-year experience in the molecular diagnosis of BAP1-TPDS, along with a clinical update and cascade genetic testing of previously reported BAP1-TPDS patients and their relatives. Specifically, we sequenced germline DNA samples from 101 individuals with suspected BAP1-TPDS and validated pathogenic variants (PVs) by assessing BAP1 somatic loss in matching tumor specimens. Overall, we identified seven patients (7/101, 6.9%) carrying six different germline BAP1 PVs, including one novel variant. Consistently, cascade testing revealed a total of seven BAP1 PV carriers. In addition, we explored the mutational burden of BAP1-TPDS tumors by targeted next-generation sequencing. Lastly, we found that certain tumors present in PV carriers retain a wild-type BAP1 allele, suggesting a sporadic origin of these tumors or a functional role of heterozygous BAP1 in neoplastic development. Altogether, our findings have important clinical implications for therapeutic response of BAP1-TPDS patients.}, } @article {pmid35883451, year = {2022}, author = {Pandey, SK and Machlof-Cohen, R and Santhanam, M and Shteinfer-Kuzmine, A and Shoshan-Barmatz, V}, title = {Silencing VDAC1 to Treat Mesothelioma Cancer: Tumor Reprograming and Altering Tumor Hallmarks.}, journal = {Biomolecules}, volume = {12}, number = {7}, pages = {}, pmid = {35883451}, issn = {2218-273X}, mesh = {Animals ; Apoptosis ; Humans ; Inflammation ; *Mesothelioma/genetics/therapy ; Mice ; *Nanotubes, Carbon ; RNA, Small Interfering/metabolism ; Tumor Microenvironment ; Voltage-Dependent Anion Channel 1/genetics/metabolism ; }, abstract = {Mesothelioma, an aggressive cancer with a poor prognosis, is linked to asbestos exposure. However, carbon nanotubes found in materials we are exposed to daily can cause mesothelioma cancer. Cancer cells reprogram their metabolism to support increased biosynthetic and energy demands required for their growth and motility. Here, we examined the effects of silencing the expression of the voltage-dependent anion channel 1 (VDAC1), controlling the metabolic and energetic crosstalk between mitochondria and the rest of the cell. We demonstrate that VDAC1 is overexpressed in mesothelioma patients; its levels increase with disease stage and are associated with low survival rates. Silencing VDAC1 expression using a specific siRNA identifying both mouse and human VDAC1 (si-m/hVDAC1-B) inhibits cell proliferation of mesothelioma cancer cells. Treatment of xenografts of human-derived H226 cells or mouse-derived AB1 cells with si-m/hVDAC1-B inhibited tumor growth and caused metabolism reprogramming, as reflected in the decreased expression of metabolism-related proteins, including glycolytic and tricarboxylic acid (-)cycle enzymes and the ATP-synthesizing enzyme. In addition, tumors depleted of VDAC1 showed altered microenvironments and inflammation, both associated with cancer progression. Finally, tumor VDAC1 silencing also eliminated cancer stem cells and induced cell differentiation to normal-like cells. The results show that silencing VDAC1 expression leads to reprogrammed metabolism and to multiple effects from tumor growth inhibition to modulation of the tumor microenvironment and inflammation, inducing differentiation of malignant cells. Thus, silencing VDAC1 is a potential therapeutic approach to treating mesothelioma.}, } @article {pmid35880098, year = {2022}, author = {Di Marzio, N and Ananthanarayanan, P and Guex, AG and Alini, M and Riganti, C and Serra, T}, title = {Sound-based assembly of a microcapillary network in a saturn-like tumor model for drug testing.}, journal = {Materials today. Bio}, volume = {16}, number = {}, pages = {100357}, pmid = {35880098}, issn = {2590-0064}, abstract = {The tumor microenvironment (TME), consisting of extracellular matrix, proteins, stromal cells, and a vascular system, is reported to have a key role in cancer progression and prognosis. Thereby, the interaction between the vascular network and tumor mass is an important feature of the TME since the anticancer agents which are delivered to the TME can trigger the vascular response and influence the therapeutic outcome of the treatment. To identify and develop new therapeutic strategies, 3D in vitro models that recapitulate the complexity of the TME are urgently needed. Among them, vascularized tumor models are a promising approach, allowing to target tumor angiogenesis and reduce tumor growth. By using sound patterning, cells can be condensed locally into highly reproducible patterns through the action of mild hydrodynamic forces. Here, we use a soundwave-driven cell assembly approach to create a ring-shaped microcapillary network in fibrin hydrogel. Then, we generate a 3D vascularized tumor model by combining a tumor heterotypic spheroid, consisting of fibroblasts and Malignant Pleural Mesothelioma (MPM) cells, with the surrounding vascular ring. Based on its shape, we name it Saturn-like vascularized Tumor Model (STM). The growth of the microcapillary network is monitored over time by fluorescence imaging. The area covered by the microcapillary network, and its continuous increase in presence of the heterotypic tumor spheroid was monitored. Interestingly, this effect is enhanced when treating the STM with the anticancer agent Cisplatin. Overall, we show the use of sound patterning as a fast and cell-friendly approach to spatially organize and condense cells, to generate a 3D in vitro platform from which simple readouts of drug tests can be extracted by image analysis, with the potential to provide a model system for tailored tumor therapy.}, } @article {pmid35876593, year = {2022}, author = {Urban, M and Pelclová, D and Urban, P and Vít, M and Urban, P and Fenclová, Z}, title = {Asbestos danger in central Europe is not yet over - the situation in the Czech Republic.}, journal = {Central European journal of public health}, volume = {30}, number = {2}, pages = {67-73}, pmid = {35876593}, issn = {1210-7778}, mesh = {*Asbestos/toxicity ; Asbestosis/epidemiology ; Czech Republic/epidemiology ; Humans ; Lung Neoplasms/epidemiology ; Mesothelioma/epidemiology ; *Occupational Diseases/epidemiology ; *Occupational Exposure/adverse effects ; Retrospective Studies ; }, abstract = {OBJECTIVES: In the Czech Republic, asbestos has been classified as a known human carcinogen since 1984. The use of asbestos-containing products was limited to scenarios where the use of other materials was not possible. Since 1997, the manufacture of asbestos materials has been forbidden, and in 1999, the import, manufacture and distribution of all types of asbestos fibres was legally banned by Act No. 157/1998 Coll. Although the use of asbestos is forbidden, the risk of exposure still exists given the ongoing demolition and reconstruction of buildings in which asbestos has been used. In addition, a novel risk has arisen through the quarrying of asbestos-containing aggregates and their subsequent use. The aim of this paper was to describe and evaluate asbestos in terms of history, legislation, current risk of occupational exposure and its health consequences in the Czech Republic over the last three decades.

METHODS: This retrospective descriptive study used the collected data on occupational exposure and occupational diseases. The counts of workers occupationally exposed to asbestos were obtained from the Registry of Work Categorization; the numbers and structure of occupational diseases caused by asbestos were taken from the Czech National Registry of Occupational Diseases. Data on the total number of mesothelioma cases recorded in the Czech National Cancer Registry was provided by the Institute of Health Information and Statistics of the Czech Republic.

RESULTS: A total of 13,112 subjects were registered as occupationally exposed to asbestos during the period 2001-2020. A total of 687 cases of asbestos-related occupational diseases were reported in the period 1991-2020 in the Czech Republic, comprising 178 cases of asbestosis, 250 cases of pleural hyalinosis, 168 cases of pleural or peritoneal mesothelioma, 90 cases of lung cancer, and one case of laryngeal cancer. The data from the Czech National Cancer Registry, available for a shorter period (1991-2018), reveal 1,389 cases of mesothelioma, of which only ~11% were recognised as occupational, despite the fact that the occupational causality of mesotheliomas is estimated to be up to 90% of mesotheliomas. Moreover, the latency of mesotheliomas since the last occupational exposure reached up to 50 years and this trend is still slightly increasing, unlike asbestosis, where a high cumulative dose of inhaled asbestos is needed. The real proportion of occupational lung cancers may obviously be even higher, especially in smokers, where occupational causes including asbestos are not suspected by most physicians.

CONCLUSION: Czech data on asbestos-related occupational diseases, especially cancers, are grossly underestimated, which is most apparent through the low proportion of mesotheliomas diagnosed as occupational. Asbestos materials in older buildings remained in situ and may represent a danger during reconstruction works. The current source of exposure appears to be quarrying of asbestos-containing aggregate and its subsequent use. Awareness of the professional community is therefore crucial, not only for the possibility of compensating those affected, but also for the early detection of the diseases through the dispensary of exposed persons.}, } @article {pmid35874636, year = {2022}, author = {Mazzoni, E and Bononi, I and Rotondo, JC and Mazziotta, C and Libener, R and Guaschino, R and Gafà, R and Lanza, G and Martini, F and Tognon, M}, title = {Sera from Patients with Malignant Pleural Mesothelioma Tested Positive for IgG Antibodies against SV40 Large T Antigen: The Viral Oncoprotein.}, journal = {Journal of oncology}, volume = {2022}, number = {}, pages = {7249912}, pmid = {35874636}, issn = {1687-8450}, abstract = {Malignant pleural mesothelioma (MPM), a fatal tumor, is mainly linked to the asbestos exposure. It has been reported that together with the inhalation of asbestos fibers, other factors are involved in the MPM onset, including simian virus 40 (SV40). SV40, a polyomavirus with oncogenic potential, induces (i) in vitro the mesenchymal cell transformation, whereas (ii) in vivo the MPM onset in experimental animals. The association between MPM and SV40 in humans remains to be elucidated. Sera (n = 415) from MPM-affected patients (MPM cohort 1; n = 152) and healthy subjects (HSs, n = 263) were investigated for their immunoglobulin G (IgG) against simian virus 40 large tumor antigen (Tag), which is the transforming protein. Sera were investigated with an indirect enzyme-linked immunosorbent assay (ELISA) using two synthetic peptides from SV40 Tag protein. SV40 Tag protein was evaluated by immunohistochemical (IHC) staining on MPM samples (MPM cohort 2; n = 20). Formalin-fixed and paraffin-embedded (FFPE) samples were obtained from MPM patients unrelated to MPM serum donors. The proportion of sera, from MPM patients, showing antibodies against SV40 Tag (34%) was significantly higher compared to HSs (20%) (odds ratio 2.049, CI 95% 1.32-3.224; p=0.0026). Immunohistochemical staining (IHS) assays showed SV40 Tag expression in 8/20, 40% of MPM specimens. These results indicate that SV40 is linked to a large fraction of MPM. It is worth noting that the prevalence of SV40 Tag antibodies detected in sera from cohort 1 of MPM patients is similar to the prevalence of SV40 Tag found to be expressed in FFPE tissues from MPM cohort 2.}, } @article {pmid35863303, year = {2022}, author = {Thives, LP and Ghisi, E and Thives Júnior, JJ and Vieira, AS}, title = {Is asbestos still a problem in the world? A current review.}, journal = {Journal of environmental management}, volume = {319}, number = {}, pages = {115716}, doi = {10.1016/j.jenvman.2022.115716}, pmid = {35863303}, issn = {1095-8630}, mesh = {*Asbestos ; Commerce ; Humans ; International Cooperation ; *Mesothelioma/epidemiology/etiology ; *Occupational Exposure ; }, abstract = {Asbestos has been used by automobile, construction, manufacturing, power, and chemical industries for many years due to its particular properties, i.e. high tensile strength, non-flammable, thermal and electrical resistance and stability, and chemical resistance. However, such a mineral causes harmful effects to human health, including different types of cancer (e.g., mesothelioma). As a result, the use of asbestos has been banned since the 1980s in many countries. Nonetheless, asbestos is still part of the daily life of the population as asbestos-containing materials (ACMs) are still present in many buildings constructed and renovated before the 1990s. This work aims to present a current literature review about asbestos. The literature review was composed mainly of research articles published in international journals from the medical and engineering disciplines to provide an overview of asbestos use effects reported in interdisciplinary areas. The literature review comprised asbestos characteristics and its relationship to the risks of human exposure, countries where asbestos use is permitted or banned, reducing asbestos in the built environment, and environmental impact due to use and disposal of asbestos. The main findings were that ACMs are still responsible for severe human diseases, particularly in areas where there is a lack of coordinated asbestos management plans, reduced awareness about asbestos health risks, or even a delay in the implementation of asbestos-ban. Such issues may be more prevailing in developing countries. The current research in many countries contemplates several methodologies and techniques to process ACMs into inert and recyclable materials. The identification and coordinated management of ACM hazardous waste is a significant challenge to be faced by countries, and its inadequate disposal causes severe risk of exposure to asbestos fibres. Based on this work, it was concluded that banning asbestos is indicated in all countries in the world.}, } @article {pmid35859704, year = {2022}, author = {Kumar, N and Natrayan, L and Kasirajan, G and Kaliappan, S and Raj Kamal, MD and Patil, PP and Chewaka, MD}, title = {Development of Novel Bio-mulberry-Reinforced Polyacrylonitrile (PAN) Fibre Organic Brake Friction Composite Materials.}, journal = {Bioinorganic chemistry and applications}, volume = {2022}, number = {}, pages = {6426763}, pmid = {35859704}, issn = {1565-3633}, abstract = {Natural fibre reinforcement is used in important sectors such as medical, aerospace, automobile, and many other fields. Many articles have reported that natural fibre has the potential to replace synthetic fibres. Natural fibre reinforcement has given good results as a brake friction material. It has already been proven that asbestos causes lung cancer and mesothelioma in brakes. Many people died from the effects of asbestos. According to the World Health Organization's trending brake report, this material leads to serious health issues. This work is going on for the replacement of these materials. Mulberry fibre is a unique material, and PAN fibre is combined with mulberry fibre and used as a brake reinforcement material to replace Kevlar fibre. The brake pads were fabricated with the various wt% of mulberry fibres and PAN fibre [3-12%] with an equal ratio and aramid fibre [3-6%] in the hydraulic hind brake moulding machine. The mechanical, chemical, physical, tribological, and thermal properties were evaluated. MF-2 [6 wt%] mulberry-PAN-fibre-based brake pad composites have shown better results for ultimate shear strength and proof stress, tensile strength, compressive strength, and impact energy.}, } @article {pmid35852497, year = {2022}, author = {Price, B}, title = {Projection of future numbers of mesothelioma cases in the US and the increasing prevalence of background cases: an update based on SEER data for 1975 through 2018.}, journal = {Critical reviews in toxicology}, volume = {52}, number = {4}, pages = {317-324}, doi = {10.1080/10408444.2022.2082919}, pmid = {35852497}, issn = {1547-6898}, mesh = {*Asbestos/toxicity ; Humans ; Incidence ; *Mesothelioma/epidemiology ; *Mesothelioma, Malignant ; *Pleural Neoplasms/epidemiology/etiology/pathology ; Prevalence ; }, abstract = {Historically, mesothelioma, which is almost exclusively a cancer of the pleura or peritoneum, has been referred to as a sentinel disease for asbestos exposure meaning that the disease is an epidemiologic marker for asbestos. This description of mesothelioma often has been misinterpreted to mean that the only risk factor for mesothelioma is asbestos. In addition to a few risk factors other than asbestos, in the US, background mesotheliomas, i.e. mesothelioma cases that are a consequence of spontaneous tumor formation, are the most prevalent number of cases after asbestos-associated cases.[1] My analysis of SEER data for 1973 through 2005 published in 2009 projected that around 2040 virtually all mesothelioma cases in the US will be background cases. The update here, which is based on the most current SEER data, 1975 through 2018, and the same methods used in 2009 shows that the pattern of mesothelioma incidence is unchanged. Further, in general agreement with the analysis published in 2009, after 2040 virtually all mesothelioma cases, currently estimated to be approximately 1600 per year, will be background cases.}, } @article {pmid35840292, year = {2022}, author = {Henshall, C and Dawson, P and Rahman, N and Ball, H and Sundralingam, A and Shahidi, M and McKeown, E and Park, J and Walthall, H and Davey, Z}, title = {Understanding clinical decision-making in mesothelioma care: a mixed methods study.}, journal = {BMJ open respiratory research}, volume = {9}, number = {1}, pages = {}, pmid = {35840292}, issn = {2052-4439}, mesh = {*COVID-19 ; Clinical Decision-Making ; Humans ; *Mesothelioma/diagnosis ; *Mesothelioma, Malignant ; State Medicine ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma is a rare, incurable cancer arising from previous asbestos exposure; patients have a poor prognosis, with a median survival rate of 8-14 months. Variation in mesothelioma clinical decision-making remains common with a lack of multidisciplinary knowledge sharing, leading to inconsistencies in treatment decisions. The study aimed to explore which factors impacted on clinicians' decision-making in mesothelioma care, with a view to optimising the mesothelioma care pathway.

METHODS: This mixed methods study consisted of documentary analysis of local and national guidelines, policies or documents pertaining to mesothelioma care pathways, secondary analysis of mesothelioma patient data, and interviews with clinicians attending lung cancer and/or mesothelioma-specific multidisciplinary team meetings. The study took place at three National Health Service trusts in England. Documentations relating to patients' treatment pathways were collated and reviewed qualitatively. Records of patients with mesothelioma were extracted from hospital patient records and data collected on diagnosis date, treatment, mortality rates, survival postdiagnosis, age and clinical care team. Data were statistically analysed. Interviews with clinicians explored influences on clinical decision-making, including challenges or barriers involved. Data were thematically analysed. The Strengthening the Reporting of Observational Studies in Epidemiology reporting checklist was used.

RESULTS: There were differences in the structure and delivery of mesothelioma treatment and care between trusts. Four main themes were identified: 'collaboration and communication', 'evidence base and knowledge', 'role of the clinician' and 'role of the patient'. Two cross-cutting themes relating to the role of the mesothelioma nurse specialist and the impact of COVID-19 were identified.

DISCUSSION: There is a need to review the structure of mesothelioma multidisciplinary team meetings to ensure patients are reviewed by clinicians with appropriate knowledge, expertise and understanding of how, why and when decisions should be made. There is a need for expert clinicians in mesothelioma care to promote an up-to-date evidence and knowledge base within the wider multidisciplinary team.}, } @article {pmid35815188, year = {2022}, author = {Ma, GY and Shi, S and Wang, P and Wang, XG and Zhang, ZG}, title = {Clinical significance of 9P21 gene combined with BAP1 and MTAP protein expression in diagnosis and prognosis of mesothelioma serous effusion.}, journal = {Biomedical reports}, volume = {17}, number = {2}, pages = {66}, pmid = {35815188}, issn = {2049-9442}, abstract = {The diagnostic value of the 9P21 gene determined using fluorescence in situ hybridization (FISH) combined with BRCA1-associated protein 1 (BAP1) and methylthioadenosine phosphorylase (MTAP) expression detection by immunohistochemistry, was investigated in serous effusion samples of malignant mesothelioma. A total of 70 serous disease samples with serous effusion were collected from June 2017 to June 2020. Following biopsy specimen pathological diagnosis, samples were divided into malignant mesothelioma and benign mesothelioma. Differential expression of BAP1 and MTAP genes were identified in mesothelioma and mesenchymal hyperplasia. The 9P21 gene fragment was lost in mesothelioma. The positive rates of FISH, BAP1 and MTAP in biopsy specimens were 98.00, 94.00 and 90.00%. The specificity of the three were 96.00, 85.71 and 77.27%, the sensitivity were 90.00, 95.92 and 93.75%, and the positive rate of the combined detection of the three was 93.33%. The positive rate of serous fluid samples detected by the three methods (9P21 FISH probe combined with BAP1 and MTAP expression detected immunohistochemically) was 96.00, 92.00 and 88.00%, the specificity were 90.00, 77.27 and 71.43%, the sensitivity was 96.00, 93.75 and 89.80%, and the positive rate of the three combined detections was 91.33%. It was demonstrated that there was a high consistency between serous fluid samples and biopsy samples. According to clinicopathological analysis, sex, age, lesion site, Ki67 had little association with the occurrence and development of malignant mesothelioma, while asbestos exposure history was closely associated to the occurrence of mesothelioma. A high level of BAP1 gene was positively associated with the prognosis of mesothelioma, while a high level of MTAP gene was negatively associated with the prognosis of mesothelioma (P<0.05). Therefore, 9P21 FISH probe combined with BAP1 and MTAP can be used as a new method for the detection of malignant mesothelioma, and provide an important basis for the early diagnosis of mesothelioma.}, } @article {pmid35804954, year = {2022}, author = {Janssens, E and Schillebeeckx, E and Zwijsen, K and Raskin, J and Van Cleemput, J and Surmont, VF and Nackaerts, K and Marcq, E and van Meerbeeck, JP and Lamote, K}, title = {External Validation of a Breath-Based Prediction Model for Malignant Pleural Mesothelioma.}, journal = {Cancers}, volume = {14}, number = {13}, pages = {}, pmid = {35804954}, issn = {2072-6694}, support = {grants KOTK UA/2016/10710/1 and 'Emmanuel van der Schueren'//Kom op tegen Kanker (Stand up to Cancer), the Flemish cancer society/ ; }, abstract = {During the past decade, volatile organic compounds (VOCs) in exhaled breath have emerged as promising biomarkers for malignant pleural mesothelioma (MPM). However, as these biomarkers lack external validation, no breath test for MPM has been implemented in clinical practice. To address this issue, we performed the first external validation of a VOC-based prediction model for MPM. The external validation cohort was prospectively recruited, consisting of 47 MPM patients and 76 asbestos-exposed (AEx) controls. The predictive performance of the previously developed model was assessed by determining the degree of agreement between the predicted and actual outcome of the participants (patient/control). Additionally, to optimise the performance, the model was updated by refitting it to the validation cohort. External validation revealed a poor performance of the original model as the accuracy was estimated at only 41%, indicating poor generalisability. However, subsequent updating of the model improved the differentiation between MPM patients and AEx controls significantly (73% accuracy, 92% sensitivity, and 92% negative predictive value), substantiating the validity of the original predictors. This updated model will be more generalisable to the target population and exhibits key characteristics of a potential screening test for MPM, which could significantly impact MPM management.}, } @article {pmid35804881, year = {2022}, author = {Song, Y and Baxter, SS and Dai, L and Sanders, C and Burkett, S and Baugher, RN and Mellott, SD and Young, TB and Lawhorn, HE and Difilippantonio, S and Karim, B and Kadariya, Y and Pinto, LA and Testa, JR and Shoemaker, RH}, title = {Mesothelioma Mouse Models with Mixed Genomic States of Chromosome and Microsatellite Instability.}, journal = {Cancers}, volume = {14}, number = {13}, pages = {}, pmid = {35804881}, issn = {2072-6694}, support = {HHSN261201500003C/CA/NCI NIH HHS/United States ; R01 CA148805/CA/NCI NIH HHS/United States ; HHSN261201500003I/CA/NCI NIH HHS/United States ; CA06927/CA/NCI NIH HHS/United States ; P30 CA006927/CA/NCI NIH HHS/United States ; CA148805/CA/NCI NIH HHS/United States ; }, abstract = {Malignant mesothelioma (MMe) is a rare malignancy originating from the linings of the pleural, peritoneal and pericardial cavities. The best-defined risk factor is exposure to carcinogenic mineral fibers (e.g., asbestos). Genomic studies have revealed that the most frequent genetic lesions in human MMe are mutations in tumor suppressor genes. Several genetically engineered mouse models have been generated by introducing the same genetic lesions found in human MMe. However, most of these models require specialized breeding facilities and long-term exposure of mice to asbestos for MMe development. Thus, an alternative model with high tumor penetrance without asbestos is urgently needed. We characterized an orthotopic model using MMe cells derived from Cdkn2a[+/-];Nf2[+/-] mice chronically injected with asbestos. These MMe cells were tumorigenic upon intraperitoneal injection. Moreover, MMe cells showed mixed chromosome and microsatellite instability, supporting the notion that genomic instability is relevant in MMe pathogenesis. In addition, microsatellite markers were detectable in the plasma of tumor-bearing mice, indicating a potential use for early cancer detection and monitoring the effects of interventions. This orthotopic model with rapid development of MMe without asbestos exposure represents genomic instability and specific molecular targets for therapeutic or preventive interventions to enable preclinical proof of concept for the intervention in an immunocompetent setting.}, } @article {pmid35795882, year = {2022}, author = {Tanaka, T and Asakura, S and Hisamatsu, K and Fujimoto, N}, title = {Thrombocytopenia as an Immune-Related Adverse Event in Malignant Pleural Mesothelioma: A Case Report.}, journal = {JTO clinical and research reports}, volume = {3}, number = {7}, pages = {100351}, pmid = {35795882}, issn = {2666-3643}, abstract = {A 69-year-old man presented with a pulmonary opacity at a regular medical check-up. He had been exposed to asbestos in a chemical fiber manufacturing setting. Result of positron emission tomography with computed tomography (CT) revealed fluorodeoxyglucose accumulations along the right pleura in areas with multiple nodules and irregular pleural thickening. On the basis of analysis of a CT-guided needle biopsy result, he had been diagnosed with having epithelioid malignant pleural mesothelioma. He received neoadjuvant chemotherapy, and subsequently, a pleurectomy and decortication. After 6 months, malignant pleural mesothelioma recurred with multiple tumors in the pleural cavity. Nivolumab was administered as salvage immunotherapy. A CT scan result revealed marked tumor reduction; however, his platelet count was low (8000/μL), and he was diagnosed with having nivolumab-induced immune thrombocytopenia. Oral prednisone and thrombopoietin receptor agonist were delivered, and the platelet count improved; therefore, a sustained cycle of nivolumab was resumed. This case revealed that nivolumab could be readministered for continued antitumor effects, with careful management of immune-related adverse events.}, } @article {pmid35785199, year = {2022}, author = {Kuryk, L and Rodella, G and Staniszewska, M and Pancer, KW and Wieczorek, M and Salmaso, S and Caliceti, P and Garofalo, M}, title = {Novel Insights Into Mesothelioma Therapy: Emerging Avenues and Future Prospects.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {916839}, pmid = {35785199}, issn = {2234-943X}, abstract = {Malignant mesothelioma is a rare and aggressive cancer that develops in the thin layer surrounding the mesothelium and is mainly caused by asbestos exposure. Despite improvements in patient prognosis with conventional cancer treatments, such as surgery, chemotherapy, and radiotherapy, there are still no curative treatment modalities for advanced disease. In recent years, new therapeutic avenues have been explored. Improved understanding of the mechanisms underlying the dynamic tumor interaction with the immune system has led to the development of immunotherapeutic approaches. Numerous recent clinical trials have shown a desire to develop more effective treatments that can be used to fight against the disease. Immune checkpoint inhibitors, oncolytic adenoviruses, and their combination represent a promising strategy that can be used to synergistically overcome immunosuppression in the mesothelioma tumor microenvironment. This review provides a synthesized overview of the current state of knowledge on new therapeutic options for mesothelioma with a focus on the results of clinical trials conducted in the field.}, } @article {pmid35778611, year = {2022}, author = {Fennell, DA and Dulloo, S and Harber, J}, title = {Immunotherapy approaches for malignant pleural mesothelioma.}, journal = {Nature reviews. Clinical oncology}, volume = {19}, number = {9}, pages = {573-584}, pmid = {35778611}, issn = {1759-4782}, support = {21400/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Humans ; Immunotherapy/methods ; *Lung Neoplasms/drug therapy ; *Mesothelioma/therapy ; *Mesothelioma, Malignant ; *Pleural Neoplasms/drug therapy/pathology ; Tumor Microenvironment ; *Vaccines/therapeutic use ; }, abstract = {Over the past decade, immune-checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer. In mesothelioma, a rare cancer with a dismal prognosis generally caused by exposure to asbestos, treatment with single or dual ICIs results in robust improvements in overall survival over previous standard-of-care therapies, both in the first-line and relapsed disease settings. Predictive biological features that underpin response to ICIs remain poorly understood; however, insights into the immune microenvironment and genomic landscape of mesothelioma as well as into their association with response or acquired resistance to ICIs are emerging. Several studies of rational combinations involving ICIs with either another ICI or a different agent are ongoing, with emerging evidence of synergistic antitumour activity. Non-ICI-based immunotherapies, such as peptide-based vaccines and mesothelin-targeted chimeric antigen receptor T cells, have demonstrated promising efficacy. Moreover, results from pivotal trials of dendritic cell vaccines and viral cytokine delivery, among others, are eagerly awaited. In this Review, we comprehensively summarize the key steps in the development of immunotherapies for mesothelioma, focusing on strategies that have led to randomized clinical evaluation and emerging predictors of response. We then forecast the future treatment opportunities that could arise from ongoing research.}, } @article {pmid35748766, year = {2022}, author = {Locher, BN and Barresi, F and Kuhn, BK and Vrugt, B and Bopp, M and Dressel, H}, title = {Occupations and geographical distribution of mesothelioma in Switzerland 1989-2018 - record linkage of an asbestos-exposed population with the Swiss National Cohort.}, journal = {Swiss medical weekly}, volume = {152}, number = {}, pages = {w30164}, doi = {10.4414/smw.2022.w30164}, pmid = {35748766}, issn = {1424-3997}, mesh = {*Asbestos/toxicity ; Humans ; *Mesothelioma/epidemiology/etiology/pathology ; *Mesothelioma, Malignant ; *Occupational Exposure/adverse effects ; Occupations ; *Pleural Neoplasms/epidemiology/etiology/pathology ; Switzerland/epidemiology ; }, abstract = {OBJECTIVE: We investigated the possibility of linking the data of the Swiss Laboratory for Particle Analysis (Silag), a valuable but incomplete data source in the field of asbestos-related diseases, to the Swiss National Cohort (SNC). With the resulting comprehensive dataset, we intended to provide a source for further research in the field. We also conducted preliminary analyses of data focusing on occupations and regional distribution of malignant pleural mesothelioma cases.

METHODS: Data of asbestos-exposed individuals available from the Silag were anonymously linked with the SNC by means of deterministic record linkage. From this linkage, data on occupation classified according to the international standard classification of occupations (ISCO) as well as the canton of residence in Switzerland could be retrieved.

RESULTS: Of 838 eligible individuals from the Silag data, 788 (94.0%) could be linked to the SNC database, including 476 mesothelioma cases. In 340 cases of the latter, data on occupation and industries were available. Although the majority of them were blue-collar workers, a significant proportion (n = 44, 12.9%) had executive professions. The Canton of residence in 1990 was established in 430 of subjects with mesothelioma. A cluster could be identified in eastern Switzerland, especially in the canton of Glarus.

CONCLUSIONS: It was possible to link the datasets to a large extent thereby creating a data source for further research. Of note, the linkage provided data on occupation of a selection of mesothelioma cases in Switzerland.}, } @article {pmid35743451, year = {2022}, author = {Nagamatsu, Y and Sakyo, Y and Barroga, E and Koni, R and Natori, Y and Miyashita, M}, title = {Depression and Complicated Grief, and Associated Factors, of Bereaved Family Members of Patients Who Died of Malignant Pleural Mesothelioma in Japan.}, journal = {Journal of clinical medicine}, volume = {11}, number = {12}, pages = {}, pmid = {35743451}, issn = {2077-0383}, support = {16H05579, and 21H03241//Japan Society for the Promotion of Science/ ; 210901-01//Grants-in-Aid from the Ministry of Health, Labor and Welfare, Japan,/ ; }, abstract = {OBJECTIVES: we investigated the prevalence and associated factors of depression and complicated grief (CG) among bereaved family members of malignant pleural mesothelioma (MPM) patients in Japan.

METHODS: Bereaved family members of MPM patients (n = 72) were surveyed. The Japanese version of the Patient Health Questionnaire-9 (PHQ-9) and the Japanese version of the Brief Grief Questionnaire (BGQ) were used to assess depression and complicated grief (CG), respectively. Socio-economic factors, anger toward asbestos, care satisfaction, achievement of good death, and quality of end-of-life care were assessed in relation to depression and CG.

RESULTS: In the family members of MPM patients, the frequencies of depression and CG were 19.4% and 15.3%, respectively. The bereaved family members who were not compensated by the asbestos-related health-damage relief system (p = 0.018) and who felt the financial impacts of the patient's MPM on the family (p = 0.006) had a higher likelihood of depression. The bereaved family members who were not satisfied with the care given when the patient became critical (p = 0.034), who were not compensated by the asbestos-related health-damage relief system (p = 0.020), who felt the financial impact of the patient's MPM on the family (p = 0.016), and whose deceased relative underwent surgery (p = 0.030) had a higher likelihood of CG.

CONCLUSIONS: For bereaved family members of MPM patients, routine screening for depression and CG and the provision of grief care are suggested. In addition, for family members of MPM patients, financial support, including the promotion of the asbestos-related health-damage relief system, and improved care for patients who undergo surgery and when patients become critical, are recommended.}, } @article {pmid35743417, year = {2022}, author = {Bellini, A and Mazzarra, S and Sterrantino, S and Argnani, D and Stella, F}, title = {Second Surgery for Recurrent Malignant Pleural Mesothelioma after Multimodality Treatment: A Systematic Review.}, journal = {Journal of clinical medicine}, volume = {11}, number = {12}, pages = {}, pmid = {35743417}, issn = {2077-0383}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive asbestos-related tumour with poor prognosis. To date, a multimodality treatment, including chemotherapy and surgery, with or without radiotherapy, is the gold standard therapy for selected patients with epithelioid and early-stage MPM. In this setting, the goal of surgery is to achieve the macroscopic complete resection, obtained by either extrapleural pneumonectomy or pleurectomy/decortication. Failure, in local and/or distant sites, is one of the major concerns; in fact, there has been no established treatment for the recurrence of MPM after the multimodal approach, and the role of surgery in this context is still controversial. By using electronic databases, studies that included recurrent MPM patients who underwent a second surgery were identified. The endpoints included were: a pattern of recurrence, post-recurrence survival (PRS), and the type of second surgery. When available, factors predicting better PRS and perioperative mortality and morbidity were collected. This systematic review offers an overview of the results that are currently obtained in patients undergoing a second surgery for relapsed MPM, with the aim to provide a comprehensive view on this subject that explores if a second surgery leads to an improvement in survival.}, } @article {pmid35741021, year = {2022}, author = {Pellavio, G and Martinotti, S and Patrone, M and Ranzato, E and Laforenza, U}, title = {Aquaporin-6 May Increase the Resistance to Oxidative Stress of Malignant Pleural Mesothelioma Cells.}, journal = {Cells}, volume = {11}, number = {12}, pages = {}, pmid = {35741021}, issn = {2073-4409}, mesh = {Aquaporin 6/metabolism ; Humans ; Hydrogen Peroxide/metabolism ; *Mesothelioma/diagnosis/drug therapy/genetics ; *Mesothelioma, Malignant ; Oxidative Stress ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive cancer of the pleural surface and is associated with previous asbestos exposure. The chemotherapy drug is one of the main treatments, but the median survival ranges from 8 to 14 months from diagnosis. The redox homeostasis of tumor cells should be carefully considered since elevated levels of ROS favor cancer cell progression (proliferation and migration), while a further elevation leads to ferroptosis. This study aims to analyze the functioning/role of aquaporins (AQPs) as a hydrogen peroxide (H2O2) channel in epithelial and biphasic MPM cell lines, as well as their possible involvement in chemotherapy drug resistance. Results show that AQP-3, -5, -6, -9, and -11 were expressed at mRNA and protein levels. AQP-6 was localized in the plasma membrane and intracellular structures. Compared to normal mesothelial cells, the water permeability of mesothelioma cells is not reduced by exogenous oxidative stress, but it is considerably increased by heat stress, making these cells resistant to ferroptosis. Functional experiments performed in mesothelioma cells silenced for aquaporin-6 revealed that it is responsible, at least in part, for the increase in H2O2 efflux caused by heat stress. Moreover, mesothelioma cells knocked down for AQP-6 showed a reduced proliferation compared to mock cells. Current findings suggest the major role of AQP-6 in providing mesothelioma cells with the ability to resist oxidative stress that underlies their resistance to chemotherapy drugs.}, } @article {pmid35723508, year = {2022}, author = {Lee, JT and Mittal, DL and Warby, A and Kao, S and Dhillon, HM and Vardy, JL}, title = {Dying of mesothelioma: A qualitative exploration of caregiver experiences.}, journal = {European journal of cancer care}, volume = {31}, number = {5}, pages = {e13627}, pmid = {35723508}, issn = {1365-2354}, support = {//Dust Diseases Board NSW/ ; }, mesh = {Adaptation, Psychological ; *Bereavement ; Caregivers ; Humans ; *Mesothelioma/therapy ; Palliative Care ; Qualitative Research ; }, abstract = {OBJECTIVE: To explore the experience of family caregivers of people with mesothelioma with focus on end-of-life issues.

METHODS: A qualitative sub-study using semi-structured interviews and thematic analysis.

RESULTS: Fourteen caregivers were interviewed; 11 were bereaved. The overarching theme was the impact of patients' diagnosis, treatment and death on caregivers and families. Three main themes were identified: (i) information provision and decision-making; (ii) grief and bereavement; and (iii) involvement and timing of palliative care. Caregivers initially had minimal knowledge of mesothelioma and wanted more information. Prognostic uncertainty caused distress. Grief and bereavement sub-themes were (i) coping and personal priorities; (ii) reflections on dying; and (iii) reflections on care. Caregivers highlighted the importance of creating meaningful events, having hope, 'doing something' and support from family and external sources. Reflections on dying contrasted regret after a 'bad', often unexpected death, with 'good' deaths. Care was made difficult by challenges navigating the health system and perceived gaps. Caregivers reported late referral to palliative care.

CONCLUSION: Lack of information caused challenges for caregivers. Grief and bereavement outcomes varied and may have been adversely impacted by lack of engagement with palliative care. Integrated care with lung cancer coordinators and improved palliative care access may reduce caregiver burden.}, } @article {pmid35717324, year = {2022}, author = {Migliore, E and Consonni, D and Peters, S and Vermeulen, RCH and Kromhout, H and Baldassarre, A and Cavone, D and Chellini, E and Magnani, C and Mensi, C and Merler, E and Musti, M and Marinaccio, A and Mirabelli, D}, title = {Pleural mesothelioma risk by industry and occupation: results from the Multicentre Italian Study on the Etiology of Mesothelioma (MISEM).}, journal = {Environmental health : a global access science source}, volume = {21}, number = {1}, pages = {60}, pmid = {35717324}, issn = {1476-069X}, mesh = {*Asbestos ; Case-Control Studies ; Female ; Humans ; Italy/epidemiology ; Male ; *Mesothelioma/epidemiology/etiology ; *Mesothelioma, Malignant ; *Occupational Diseases/epidemiology/etiology ; *Occupational Exposure/adverse effects ; Occupations ; *Pleural Neoplasms/epidemiology/etiology ; }, abstract = {BACKGROUND: The Italian mesothelioma registry (ReNaM) estimates mesothelioma incidence and addresses its etiology by assessing cases' exposures but cannot provide relative risk estimates.

OBJECTIVES: i) To estimate pleural mesothelioma relative risk by industry and occupation and by ReNaM categories of asbestos exposure; and ii) to provide quantitative estimates of the exposure-response relationship.

METHODS: A population-based mesothelioma case-control study was conducted in 2012-2014 in five Italian regions. Cases and age and gender frequency-matched controls were interviewed using a standard ReNaM questionnaire. Experts coded work histories according to international standard classifications of industries/occupations and assigned asbestos exposure according to ReNaM categories. Job codes were further linked to SYN-JEM, a quantitative job-exposure matrix. Cumulative exposure (CE, f/mL-years) was computed by summing individual exposures over lifetime work history. Unconditional logistic regression analyses adjusted by gender, centre and age were fitted to calculate odds ratios (OR) and 95% confidence intervals (CI).

RESULTS: Among men we observed increased risks of mesothelioma in many industries and associated occupations, including: asbestos-cement (OR = 3.43), manufacture of railroad equipment (OR = 8.07), shipbuilding and repairing (OR = 2.34), iron and steel mills (OR = 2.15), and construction (OR = 1.94). ORs by ReNaM exposure categories were as follows: definite/probable occupational exposure (OR = 15.8, men; OR = 8.80, women), possible occupational (OR = 2.82, men; OR = 3.70, women), sharing home with an exposed worker (OR = 2.55, men; OR = 10.3, women), residential (OR = 2.14, men; OR = 3.24, women). Based on SYN-JEM, mesothelioma risk increased by almost 30% per f/mL-year (OR = 1.28, CI 1.16-1.42).

CONCLUSIONS: Out study involved five regions with historically different types and levels of industrial development, encompassing one third of the Italian population and half of Italian mesothelioma cases. As expected, we found increased pleural mesothelioma risk in the asbestos industry and in trades with large consumption of asbestos materials. Clear associations were found using both qualitative (ReNaM classifications) and quantitative estimates (using SYN-JEM) of past asbestos exposure, with clear evidence of an exposure-response relationship.}, } @article {pmid35713639, year = {2022}, author = {Malpica, A and Euscher, ED and Marques-Piubelli, ML and Miranda, RN and Raghav, KP and Fournier, KF and Ramalingam, P}, title = {Localized Malignant Peritoneal Mesothelioma (LMPeM) in Women: A Clinicopathologic Study of 18 Cases.}, journal = {The American journal of surgical pathology}, volume = {46}, number = {10}, pages = {1352-1363}, doi = {10.1097/PAS.0000000000001924}, pmid = {35713639}, issn = {1532-0979}, mesh = {Adult ; Aged ; *Asbestos/adverse effects ; Female ; Homozygote ; Humans ; *Mesothelioma ; *Mesothelioma, Malignant ; Middle Aged ; MutS Homolog 2 Protein ; *Peritoneal Neoplasms/genetics ; Sequence Deletion ; }, abstract = {Localized malignant peritoneal mesothelioma is a rare tumor with limited information in the literature. In this study, we present our experience with 18 cases seen in our hospital over a period of 43 years (1978 to 2021). Patients' median age was 55 years (y) (range: 33 to 79 y) and most of them were Caucasians. Patients presented with abdominal pain (11), ascites and right leg swelling (1), abdominal mass (1), and as incidental finding (1). Thirty percent of patients reported asbestos exposure, and all patients with available information had family history of tumors; a third had personal history of tumors. Seventy-seven percent had some form of abdominopelvic surgery and/or inflammatory process. Most cases had microscopic features typically seen in malignant mesothelioma; however, some cases had confounding features such as signet-ring cells, spindle cells, clear cell changes, and adenomatoid tumor-like appearance. BAP-1 by immunohistochemistry was lost in 1/3 cases. Only 1 patient underwent genetic testing and had an MSH2 germline mutation. Homozygous deletion of CDKN2A by FISH was not found in 1 tested case, although next-generation sequencing identified a CDKN2A pathogenic mutation. 16/18 (88%) had surgical treatment, and some also received adjuvant chemotherapy. The mean overall survival (OS) of our patients was 80.4 months (95% confidence interval: 54.3-106.52); the 3-year OS was 79%, while the 5-year OS was 52.6%. Fifty-three percent of patients had recurrences and 20% had tumor progression. Although the limited sample precludes definitive conclusions, small tumor size, low-grade cytology, and low mitotic index appeared to be associated with an indolent behavior.}, } @article {pmid35703172, year = {2022}, author = {Bernstein, DM}, title = {The health effects of short fiber chrysotile and amphibole asbestos.}, journal = {Critical reviews in toxicology}, volume = {52}, number = {2}, pages = {89-112}, doi = {10.1080/10408444.2022.2056430}, pmid = {35703172}, issn = {1547-6898}, mesh = {*Asbestos ; Asbestos, Amphibole/toxicity ; Asbestos, Serpentine/toxicity ; Humans ; Lung ; *Lung Neoplasms/epidemiology ; *Mesothelioma/epidemiology ; }, abstract = {The potential toxic effects of short chrysotile and amphibole asbestos fibers with lengths <5 to ∼10 µm have been debated over the years. This stems from the large database of epidemiology, toxicology, and in-vitro studies, each of which often provides different information in understanding and differentiating the effects of short fibers. The epidemiology studies in which the cancer potency estimates were based upon relatively high exposure concentrations provide a conservative assessment that shorter fibers would have little if any effect, especially under controlled exposure or environmental conditions that may occur today. The QSAR models have shown that fiber aspect ratio and Mg content are excellent predictors of cancer potency and that short fibers/particles of amphibole would have no effect. The studies of motor vehicle mechanics and in particular workers who serviced chrysotile containing brakes with the majority of the fibers being short provides evidence that motor vehicle mechanics, including workers who were engaged in brake repair, are not at an increased risk of mesothelioma. Several inhalation toxicology studies clearly differentiated that short chrysotile and amphibole asbestos fibers did not produce a significant carcinogenic effect in the lung or pleural cavity. Because of dosing and lack of sensitivity to biosolubility, in vitro studies can be difficult to interpret; however, a number have differentiated short chrysotile and amphibole asbestos fibers from long fibers. Integral to understanding the importance of fiber length in determining possible health effects is an understanding of the biological and physiological function of the respiratory system. Short asbestos fibers, like innocuous dust, can be cleared through the tracheobronchial ciliated mucous transport, phagocytized by macrophages and cleared via the bronchial tree, and can also be removed through the lymphatic system. While the first two methods can remove them from the lung, with lymphatic transport through one-way valves, fibers are removed from the active area of the lung where the fiber-related disease has been shown to develop and can accumulate in lymphatic sumps and lymph nodes. While short asbestos fibers are present in most occupational or environmental exposures, the large body of studies strongly supports that they do not contribute to the health effects of asbestos exposure.}, } @article {pmid35670855, year = {2022}, author = {Napoli, F and Rapa, I and Izzo, S and Rigutto, A and Libener, R and Riganti, C and Bironzo, P and Taulli, R and Papotti, M and Volante, M and Scagliotti, G and Righi, L}, title = {Correction to: Micro-RNA-215 and -375 regulate thymidylate synthase protein expression in pleural mesothelioma and mediate epithelial to mesenchymal transition.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {481}, number = {2}, pages = {331}, doi = {10.1007/s00428-022-03355-y}, pmid = {35670855}, issn = {1432-2307}, } @article {pmid35665561, year = {2022}, author = {Dermawan, JK and Torrence, D and Lee, CH and Villafania, L and Mullaney, KA and DiNapoli, S and Sukhadia, P and Benayed, R and Borsu, L and Agaram, NP and Nash, GM and Dickson, BC and Benhamida, J and Antonescu, CR}, title = {EWSR1::YY1 fusion positive peritoneal epithelioid mesothelioma harbors mesothelioma epigenetic signature: Report of 3 cases in support of an emerging entity.}, journal = {Genes, chromosomes & cancer}, volume = {61}, number = {10}, pages = {592-602}, pmid = {35665561}, issn = {1098-2264}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; P50 CA140146/CA/NCI NIH HHS/United States ; P50 CA217694/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers, Tumor/genetics ; Epigenesis, Genetic ; Epigenomics ; Female ; Humans ; Male ; *Mesothelioma/genetics ; *Mesothelioma, Malignant ; Middle Aged ; *Peritoneal Neoplasms/genetics/pathology ; RNA-Binding Protein EWS/genetics ; YY1 Transcription Factor/genetics/metabolism ; Young Adult ; }, abstract = {Mesothelioma is a rare, aggressive malignant neoplasm of mesothelial origin. A small subset of peritoneal mesothelioma is driven by recurrent gene fusions, mostly EWSR1/FUS::ATF1 fusions, with predilection for young adults. To date, only two cases of mesothelioma harboring EWSR1::YY1 fusions have been described. We present three additional cases of EWSR1::YY1-fused peritoneal mesotheliomas, two localized and one diffuse, all occurring in the peritoneum of middle-aged adults (2 females and 1 male), and discovered incidentally by imaging or during surgery performed for unrelated reasons. None presented with symptoms or had a known history of asbestos exposure. All three cases were cellular epithelioid neoplasms with heterogeneous architectural patterns comprising mostly solid nests and sheets with variably papillary and trabecular areas against collagenous stroma. Cytologically, the cells were monomorphic, polygonal, epithelioid cells with dense eosinophilic cytoplasm and centrally located nuclei. Overt mitotic activity or tumor necrosis was absent. All cases showed strong diffuse immunoreactivity for pancytokeratin, CK7, and nuclear WT1, patchy to negative calretinin, retained BAP1 expression, and were negative for Ber-EP4 and MOC31. RNA-sequencing confirmed in-frame gene fusion transcripts involving EWSR1 exon 7/8 and YY1 exon 2/3. By unsupervised clustering analysis, the methylation profiles of EWSR1::YY1-fused mesotheliomas clustered similarly with EWSR1/FUS::ATF1-fused mesotheliomas and conventional mesotheliomas, suggesting a mesothelioma epigenetic signature. All three patients underwent surgical resection or cytoreductive surgery of the masses. On follow-up imaging, no recurrence or progression of disease was identified. Our findings suggest that EWSR1::YY1-fusion defines a small subset of peritoneal epithelioid mesothelioma in middle-aged adults without history of asbestos exposure.}, } @article {pmid35664766, year = {2022}, author = {Usuda, K and Niida, Y and Ishikawa, M and Iwai, S and Yamagata, A and Iijima, Y and Motono, N and Yamada, S and Uramoto, H}, title = {Genomics of Tumor Origin and Characteristics for Adenocarcinoma and Malignant Pleural Mesothelioma: A Case Report.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {858094}, pmid = {35664766}, issn = {2234-943X}, abstract = {A female underwent a right middle lobectomy for a pulmonary adenocarcinoma (AD). She eventually died of a right malignant pleural mesothelioma (MPM; sarcomatoid type) 4 years and 7 months after the removal of the AD even though she did not have any history of asbestos exposure, smoking, or radiation exposure. Her chest CT revealed multiple pulmonary nodules and bilateral pleural effusion with a right pleural tumor directly invading into the abdominal cavity. The genomics of tumor origin and characteristics were examined for the AD and the MPM. As a result, 50 somatic variants were detected in the AD, and 29 somatic variants were detected in the MPM. The variants which were common in both the AD and the MPM were not present, which suggested that the AD and the MPM had occurred independently in different origins. The MPM had two driver oncogenes of TP53 and EP300, but the AD did not. Two driver oncogenes of TP53 and EP300 were hypothesized to make the MPM aggressive. The speed at which the MPM progressed without the patient having a history of asbestos exposure, smoking, or radiation exposure was alarming.}, } @article {pmid35659582, year = {2022}, author = {Barbieri, PG and Consonni, D and Somigliana, A}, title = {Asbestos Lung Burden Does Not Predict Survival in Malignant Pleural Mesothelioma: A Necropsy-Based Study of 185 Cases.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {17}, number = {8}, pages = {1042-1049}, doi = {10.1016/j.jtho.2022.05.010}, pmid = {35659582}, issn = {1556-1380}, mesh = {*Asbestos ; Humans ; Italy/epidemiology ; Lung/pathology ; *Lung Neoplasms/pathology ; *Mesothelioma/pathology ; *Mesothelioma, Malignant ; *Occupational Exposure ; *Pleural Neoplasms/pathology ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma is an asbestos-related disease with poor survival. The prognostic role of histologic subtype is well established. Some studies (without a biological hypothesis) suggested that higher asbestos lung burden is associated with reduced survival.

METHODS: We selected subjects from two series of necropsies: residents in Brescia province (North-West Italy) and workers (or persons living with them) employed in the Monfalcone shipyards (North-East Italy). Asbestos fibers and asbestos bodies in lung samples were counted using a scanning electron and an optical microscope, respectively. Separately in the two series, we analyzed median survival time and fitted multivariable Cox regression models (adjusted for sex, period and age at diagnosis, and histopatholocical diagnosis) to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for three levels of asbestos fiber counts (reference: <1 million fibers/g of dry lung tissue).

RESULTS: We analyzed 185 necropsies, 83 in Brescia and 102 in Monfalcone. Despite a much higher lung burden in Monfalcone patients, median survival was slightly shorter in Brescia (8.3 mo) than in Monfalcone (10.2 mo). In Brescia, medium (1.0-9.9) and high (10+) fiber burden HRs were 0.91 (95% CI: 0.54-1.53) and 1.23 (95% CI: 0.41-3.70), respectively. In Monfalcone, the corresponding HRs were 1.18 (95% CI: 0.59-2.35) and 1.63 (95% CI: 0.77-3.45), respectively.

CONCLUSIONS: No relationship between asbestos lung burden and survival was found. Histologic subtype was the strongest prognostic determinant.}, } @article {pmid35650101, year = {2022}, author = {Tomita, R and Nishijo, N and Hayama, T and Fujioka, T}, title = {Discrimination of Malignant Pleural Mesothelioma Cell Lines Using Amino Acid Metabolomics with HPLC.}, journal = {Biological & pharmaceutical bulletin}, volume = {45}, number = {6}, pages = {724-729}, doi = {10.1248/bpb.b21-00972}, pmid = {35650101}, issn = {1347-5215}, mesh = {Amino Acids ; Cell Line, Tumor ; Chromatography, High Pressure Liquid ; Humans ; *Mesothelioma/metabolism ; *Mesothelioma, Malignant ; Metabolomics ; *Pleural Neoplasms/diagnosis/metabolism/pathology ; }, abstract = {Malignant pleural mesothelioma (MPM) is a malignancy closely associated with asbestos exposure. Although early diagnosis provides a chance of effective treatment and better prognosis, invasive biopsy and cytological procedure are required for definitive diagnosis. In this study, we developed a method to differentiate between MPM and control cell lines, named "amino acid metabolomics," consisting in the assessment of the balance of their amino acid levels in the cell culture medium. Culture media of MESO-1 (MPM cell line) and Met-5A (control) cells were used in this study to evaluate amino acid levels using HPLC, following the fluorescence derivatization method. The time-dependent changes in amino acid levels were visualized on the score plot following principal component analysis, and the results revealed differential changes in amino acid levels between the two cell culture supernatants. A discriminative model based on linear discriminant analysis could distinguish MPM and control cells.}, } @article {pmid35649637, year = {2022}, author = {Johnson, M and Allmark, P and Tod, A}, title = {Living beyond expectations: a qualitative study into the experience of long-term survivors with pleural mesothelioma and their carers.}, journal = {BMJ open respiratory research}, volume = {9}, number = {1}, pages = {}, pmid = {35649637}, issn = {2052-4439}, mesh = {Caregivers ; Cross-Sectional Studies ; Humans ; *Mesothelioma/therapy ; *Mesothelioma, Malignant ; Motivation ; Survivors ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is characterised by poor prognosis and limited treatment options. However, a minority of patients can survive well beyond these bleak estimates. Little is known about the specific experiences and needs of long-term survivors and families.

STUDY PURPOSE: The study aimed to gain in-depth understanding of the experiences of patients diagnosed with MPM 3 or more years, along with their main carer, and to determine the care and support needs of this group.

PARTICIPANTS AND SETTING: People diagnosed with MPM 3 or more years were recruited via asbestos and mesothelioma social media and support groups. Potential participants were asked to identify someone who acted as their main carer.

METHOD: The study employed a cross-sectional qualitative interview design. A topic guide aided a conversational interview style, conducted remotely and recorded. Patient and carer pairs were interviewed jointly when possible, but were given an option for separate interviews if preferred. Fifteen patients, with 14 identifying a main carer, consented to participation.

ANALYSIS: Recorded interviews were transcribed verbatim, and then anonymised by the interviewer. Framework analysis was used to analyse the data iteratively and to develop final themes.

FINDINGS: Three themes were developed. Participants 'Living beyond expectations' remained acutely aware that MPM was incurable, but developed a range of coping strategies. Periods of disease stability were punctuated with crises of progression or treatment ending, straining coping. 'Accessing treatment' was important for patients and carers, despite the associated challenges. They were aware options were limited, and actively sought new treatments and clinical trials. 'Support needs' were met by healthcare professionals, voluntary groups and social media networks.

CONCLUSIONS: Managing patients via regional MPM multidisciplinary teams, facilitating equal access to treatment and trials, could reduce patient and carer burden. Greater awareness and support around crisis points for this group could improve care.}, } @article {pmid35642773, year = {2022}, author = {Taeger, D and Wichert, K and Lehnert, M and Casjens, S and Pesch, B and Weber, DG and Brüning, T and Johnen, G and Behrens, T}, title = {Lung cancer and mesothelioma risks in a prospective cohort of workers with asbestos-related lung or pleural diseases.}, journal = {American journal of industrial medicine}, volume = {65}, number = {8}, pages = {652-659}, doi = {10.1002/ajim.23401}, pmid = {35642773}, issn = {1097-0274}, mesh = {*Asbestos/adverse effects ; Humans ; Lung ; *Lung Neoplasms/chemically induced/etiology ; Male ; *Mesothelioma/chemically induced/etiology ; *Mesothelioma, Malignant ; *Occupational Diseases/chemically induced/etiology ; *Occupational Exposure/adverse effects ; *Pleural Diseases/chemically induced/etiology ; *Pleural Neoplasms/epidemiology/etiology ; Prospective Studies ; }, abstract = {BACKGROUND: Asbestos causes mesothelioma and lung cancer. In the European Union, asbestos was banned in 2005, but it is still in use in many other countries. The aim of this study was to estimate the lung cancer and mesothelioma incidence risk of men with benign asbestos-related lung or pleural diseases.

METHODS: Between 2008 and 2018, 2439 male participants of a German surveillance program for asbestos workers were included in the cohort. All participants had a recognized occupational asbestos-related disease of the pleura or lung. We estimated the mesothelioma and lung cancer risks by calculating standardized incidence ratios (SIR) with corresponding 95% confidence intervals (95% CI).

RESULTS: We observed 64 incident lung cancer and 40 mesothelioma cases in the cohort. An SIR of 17.60 (95% CI: 12.57-23.96) was estimated for mesothelioma and 1.27 (95% CI: 0.98-1.62) for lung cancer. The presence of pleural plaques was associated with a strongly increased risk (SIR: 13.14; 95% CI: 8.51-19.40) for mesothelioma, but not for lung cancer (SIR: 1.05; 95% CI: 0.76-1.41). The highest lung-cancer risk (SIR: 2.56; 95% CI 1.10-5.04) was revealed for cohort members with less than 40 years since first asbestos exposure. Lung cancer risks by duration of asbestos exposure did not show a consistent time trend, but for time since last exposure a trend for mesothelioma was seen.

CONCLUSIONS: Compared to the general population, we demonstrated an association between benign asbestos-related lung or pleural disease and mesothelioma risk in workers with a history of occupational asbestos exposure. Because lung-cancer risk is dominated by smoking habits, a possible effect of asbestos exposure may have been masked. Efforts should be made to ban production and use of asbestos worldwide and to establish safe handling rules of legacy asbestos.}, } @article {pmid35637829, year = {2022}, author = {Rhazari, M and Moueqqit, O and Gartini, S and El Morabit, S and Diani, S and Aharmim, M and Thouil, A and Kouismi, H and El Bourkadi, JE}, title = {Unexplained Pleural Effusion Leads to the Revelation of a Malignant Mesothelioma: A Case Report.}, journal = {Cureus}, volume = {14}, number = {4}, pages = {e24478}, pmid = {35637829}, issn = {2168-8184}, abstract = {Malignant mesothelioma is a rare and aggressive cancer that usually affects subjects with prior asbestos exposure, a major risk factor that has been widely known as carcinogenic, and its use is now controlled if not banned in many areas of the world. Malignant mesothelioma originates from mesothelial surface cells covering the serous cavities, and the pleura is its most common site. Malignant pleural mesothelioma (MPM) typically presents with pleural effusion and chest wall pain with wide pleural thickening at radiological investigation. Although the histological examination along with immunohistochemistry helps yield the diagnosis, clinicians and experts face many challenges in diagnosing malignant mesothelioma not only due to the rarity of the disease but also due to the similarities that the disease share with other malignancies. Here, we report a case of a 55-year-old male patient with a history of chronic asbestos work exposure for 12 years who initially presented with unexplained pleural effusion and chest wall pain and was lost to follow-up but came back later with a worsening clinical state. This case is specially presented to raise awareness against cases of unexplained pleural effusion and chest pain.}, } @article {pmid35637530, year = {2022}, author = {Creaney, J and Patch, AM and Addala, V and Sneddon, SA and Nones, K and Dick, IM and Lee, YCG and Newell, F and Rouse, EJ and Naeini, MM and Kondrashova, O and Lakis, V and Nakas, A and Waller, D and Sharkey, A and Mukhopadhyay, P and Kazakoff, SH and Koufariotis, LT and Davidson, AL and Ramarao-Milne, P and Holmes, O and Xu, Q and Leonard, C and Wood, S and Grimmond, SM and Bueno, R and Fennell, DA and Pearson, JV and Robinson, BW and Waddell, N}, title = {Comprehensive genomic and tumour immune profiling reveals potential therapeutic targets in malignant pleural mesothelioma.}, journal = {Genome medicine}, volume = {14}, number = {1}, pages = {58}, pmid = {35637530}, issn = {1756-994X}, mesh = {Genomics ; Humans ; *Lung Neoplasms/genetics ; *Mesothelioma/genetics ; *Mesothelioma, Malignant ; *Pleural Neoplasms/genetics/pathology ; Tumor Microenvironment/genetics ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) has a poor overall survival with few treatment options. Whole genome sequencing (WGS) combined with the immune features of MPM offers the prospect of identifying changes that could inform future clinical trials.

METHODS: We analysed somatic mutations from 229 MPM samples, including previously published data and 58 samples that had undergone WGS within this study. This was combined with RNA-seq analysis to characterize the tumour immune environment.

RESULTS: The comprehensive genome analysis identified 12 driver genes, including new candidate genes. Whole genome doubling was a frequent event that correlated with shorter survival. Mutational signature analysis revealed SBS5/40 were dominant in 93% of samples, and defects in homologous recombination repair were infrequent in our cohort. The tumour immune environment contained high M2 macrophage infiltrate linked with MMP2, MMP14, TGFB1 and CCL2 expression, representing an immune suppressive environment. The expression of TGFB1 was associated with overall survival. A small subset of samples (less than 10%) had a higher proportion of CD8 T cells and a high cytolytic score, suggesting a 'hot' immune environment independent of the somatic mutations.

CONCLUSIONS: We propose accounting for genomic and immune microenvironment status may influence therapeutic planning in the future.}, } @article {pmid35636988, year = {2022}, author = {Porcel, JM}, title = {Pleural mesothelioma.}, journal = {Medicina clinica}, volume = {159}, number = {5}, pages = {240-247}, doi = {10.1016/j.medcli.2022.03.007}, pmid = {35636988}, issn = {1578-8989}, mesh = {Biomarkers, Tumor/metabolism ; Homozygote ; Humans ; In Situ Hybridization, Fluorescence ; *Lung Neoplasms/diagnosis/genetics/therapy ; *Mesothelioma/diagnosis/genetics/therapy ; *Mesothelioma, Malignant ; *Pleural Neoplasms/diagnosis/genetics/therapy ; Sequence Deletion ; Tumor Suppressor Proteins/metabolism ; Ubiquitin Thiolesterase/genetics/metabolism ; }, abstract = {The diagnosis of diffuse pleural mesothelioma requires in most cases a pleural biopsy, performed either under imaging guidance (ultrasound or computed tomography) or thoracoscopy. Loss of BAP1 or MTAP expression (immunohistochemistry) and homozygous deletion of CDKN2A (fluorescence in situ hybridization) are the basic molecular markers for the diagnosis of mesothelioma. The histologic type and patient's performance status are the most important prognostic factors. Pleural effusion can be managed by the insertion of tunneled pleural catheters, either as a stand-alone measure (e.g., patients not amenable to multimodality therapy who have been diagnosed by pleural fluid cytology or image-guided biopsy) or combined with the administration of aerosolized talc during a diagnostic thoracoscopy. Immunotherapy is one of the front-line approaches in inoperable patients, particularly in biphasic or sarcomatous histologic varieties.}, } @article {pmid35634282, year = {2022}, author = {Principe, N and Aston, WJ and Hope, DE and Tilsed, CM and Fisher, SA and Boon, L and Dick, IM and Chin, WL and McDonnell, AM and Nowak, AK and Lake, RA and Chee, J and Lesterhuis, WJ}, title = {Comprehensive Testing of Chemotherapy and Immune Checkpoint Blockade in Preclinical Cancer Models Identifies Additive Combinations.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {872295}, pmid = {35634282}, issn = {1664-3224}, mesh = {Animals ; CD8-Positive T-Lymphocytes ; Fluorouracil/therapeutic use ; Humans ; *Immune Checkpoint Inhibitors ; Mice ; *Neoplasms/therapy ; Tumor Microenvironment ; Tumor Necrosis Factor-alpha/therapeutic use ; }, abstract = {Antibodies that target immune checkpoints such as cytotoxic T lymphocyte antigen 4 (CTLA-4) and the programmed cell death protein 1/ligand 1 (PD-1/PD-L1) are now a treatment option for multiple cancer types. However, as a monotherapy, objective responses only occur in a minority of patients. Chemotherapy is widely used in combination with immune checkpoint blockade (ICB). Although a variety of isolated immunostimulatory effects have been reported for several classes of chemotherapeutics, it is unclear which chemotherapeutics provide the most benefit when combined with ICB. We investigated 10 chemotherapies from the main canonical classes dosed at the clinically relevant maximum tolerated dose in combination with anti-CTLA-4/anti-PD-L1 ICB. We screened these chemo-immunotherapy combinations in two murine mesothelioma models from two different genetic backgrounds, and identified chemotherapies that produced additive, neutral or antagonistic effects when combined with ICB. Using flow cytometry and bulk RNAseq, we characterized the tumor immune milieu in additive chemo-immunotherapy combinations. 5-fluorouracil (5-FU) or cisplatin were additive when combined with ICB while vinorelbine and etoposide provided no additional benefit when combined with ICB. The combination of 5-FU with ICB augmented an inflammatory tumor microenvironment with markedly increased CD8[+] T cell activation and upregulation of IFNγ, TNFα and IL-1β signaling. The effective anti-tumor immune response of 5-FU chemo-immunotherapy was dependent on CD8[+] T cells but was unaffected when TNFα or IL-1β cytokine signaling pathways were blocked. Our study identified additive and non-additive chemotherapy/ICB combinations and suggests a possible role for increased inflammation in the tumor microenvironment as a basis for effective combination therapy.}, } @article {pmid35602795, year = {2022}, author = {Shrestha, B and Handa, R and Poudel, B and Hingorani, R}, title = {Pericardial Mesothelioma Presenting as Constrictive Pericarditis.}, journal = {Cureus}, volume = {14}, number = {4}, pages = {e24270}, pmid = {35602795}, issn = {2168-8184}, abstract = {This case report presents a 60-year-old gentleman with a significant smoking history and possible asbestos exposure who was referred to the emergency department for atrial fibrillation with a rapid ventricular rate and symptoms of heart failure. Labs showed normal brain natriuretic peptide and troponin I. His echocardiography finding suggested constrictive pericarditis with an ejection fraction of 60%. A computed tomography scan was concerning for a pericardial mass. Left and right heart catheterization hinted more toward constrictive physiology; however, some findings were concerning for restrictive physiology. Hence, cardiac magnetic resonance imaging was done, which established the diagnosis of constrictive pericarditis. Pericardiectomy was planned with a maze procedure for atrial fibrillation. However, a malignant neoplasm was seen on a frozen biopsy. Hence, surgery was limited to partial pericardiectomy, as the patient had advanced infiltrative neoplasm that had resulted in constrictive pericarditis. The final pathology report confirmed the diagnosis of malignant pericardial mesothelioma mixed type. Malignancy is usually diagnosed in an advanced stage, like in our case, due to nonspecific initial presentation. A literature review suggests that there is a lack of established consensus on treatment. The response to therapy also seems to be poor and results only in palliation of symptoms, with a median survival of six months from diagnosis despite optimum medical management.}, } @article {pmid35582652, year = {2022}, author = {Mielgo-Rubio, X and Cardeña Gutiérrez, A and Sotelo Peña, V and Sánchez Becerra, MV and González López, AM and Rosero, A and Trujillo-Reyes, JC and Couñago, F}, title = {Tsunami of immunotherapy reaches mesothelioma.}, journal = {World journal of clinical oncology}, volume = {13}, number = {4}, pages = {267-275}, pmid = {35582652}, issn = {2218-4333}, abstract = {Malignant pleural mesothelioma (MPM) is the most common type of malignant mesothelioma. It is a rare tumor linked to asbestos exposure and is associated with a poor prognosis. Until very recently, patients with advanced or unresectable disease had limited treatment options, primarily based on doublet chemotherapy with cisplatin and pemetrexed. In 2020 and 2021, after more than a decade with no major advances or new drugs, two phase III clinical trials published results positioning immunotherapy as a promising option for the first- and second-line treatment of MPM. Immunotherapy has revolutionized the treatment of many cancers and is also showing encouraging results in malignant mesothelioma. Both immune checkpoint inhibition and dual cytotoxic T-lymphocyte-associated antigen 4 and programmed death-ligand 1 pathway blockade resulted in significantly improved overall survival in randomized phase III trials. In the CheckMate 743 trial, first-line therapy with nivolumab plus ipilimumab outperformed standard chemotherapy, while in the CONFIRM trial, nivolumab outperformed placebo in patients previously treated with chemotherapy. These two trials represent a major milestone in the treatment of MPM and are set to position immunotherapy as a viable alternative for treatment-naïve patients and patients with progressive disease after chemotherapy.}, } @article {pmid35566667, year = {2022}, author = {Nagamatsu, Y and Sakyo, Y and Barroga, E and Koni, R and Natori, Y and Miyashita, M}, title = {Bereaved Family Members' Perspectives of Good Death and Quality of End-of-Life Care for Malignant Pleural Mesothelioma Patients: A Cross-Sectional Study.}, journal = {Journal of clinical medicine}, volume = {11}, number = {9}, pages = {}, pmid = {35566667}, issn = {2077-0383}, support = {16H05579//the Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (JSPS KAKENHI)/ ; 16H05579//the Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (JSPS KAKENHI)/ ; }, abstract = {OBJECTIVE: This study investigated whether malignant pleural mesothelioma (MPM) patients achieved good deaths and good quality of end-of-life care compared with other cancer patients from the perspective of bereaved family members in Japan.

METHODS: This cross-sectional study was part of a larger study on the achievement of good deaths of MPM patients and the bereavement of their family members. Bereaved family members of MPM patients in Japan (n = 72) were surveyed. The Good Death Inventory (GDI) was used to assess the achievement of good death. The short version of the Care Evaluation Scale (CES) version 2 was used to assess the quality of end-of-life care. The GDI and CES scores of MPM patients were compared with those of a Japanese cancer population from a previous study.

RESULTS: MPM patients failed to achieve good deaths. Only 12.5% of the MPM patients were free from physical pain. The GDI scores of most of the MPM patients were significantly lower than those of the Japanese cancer population. The CES scores indicated a significantly poorer quality of end-of-life care for the MPM patients than the Japanese cancer population. The total GDI and CES scores were correlated (r = 0.55).

CONCLUSIONS: The quality of end-of-life care for MPM patients remains poor. Moreover, MPM patients do not achieve good deaths from the perspective of their bereaved family members.}, } @article {pmid35565374, year = {2022}, author = {Holzknecht, A and Illini, O and Hochmair, MJ and Krenbek, D and Setinek, U and Huemer, F and Bitterlich, E and Kaindl, C and Getman, V and Akan, A and Weber, M and Leobacher, G and Valipour, A and Mueller, MR and Watzka, SB}, title = {Multimodal Treatment of Malignant Pleural Mesothelioma: Real-World Experience with 112 Patients.}, journal = {Cancers}, volume = {14}, number = {9}, pages = {}, pmid = {35565374}, issn = {2072-6694}, abstract = {Malignant pleural mesothelioma (MPM) is a rare pleural cancer associated with asbestos exposure. According to current evidence, the combination of chemotherapy, surgery and radiotherapy improves patients’ survival. However, the optimal sequence and weighting of the respective treatment modalities is unclear. In anticipation of the upcoming results of the MARS-2 trial, we sought to determine the relative impact of the respective treatment modalities on complications and overall survival in our own consecutive institutional series of 112 patients. Fifty-seven patients (51%) underwent multimodality therapy with curative intent, while 55 patients (49%) were treated with palliative intent. The median overall survival (OS) of the entire cohort was 16.9 months (95% CI: 13.4−20.4) after diagnosis; 5-year survival was 29% for patients who underwent lung-preserving surgery. In univariate analysis, surgical treatment (p < 0.001), multimodality therapy (p < 0.001), epithelioid subtype (p < 0.001), early tumor stage (p = 0.02) and the absence of arterial hypertension (p = 0.034) were found to be prognostic factors for OS. In multivariate analysis, epithelioid subtype was associated with a survival benefit, whereas the occurrence of complications was associated with worse OS. Multimodality therapy including surgery significantly prolonged the OS of MPM patients compared with multimodal therapy without surgery.}, } @article {pmid35564776, year = {2022}, author = {Vidican, P and Perol, O and Fevotte, J and Fort, E and Treilleux, I and Belladame, E and Zavadil, J and Fervers, B and Charbotel, B}, title = {Frequency of Asbestos Exposure and Histological Subtype of Ovarian Carcinoma.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {9}, pages = {}, pmid = {35564776}, issn = {1660-4601}, support = {001/WHO_/World Health Organization/International ; }, mesh = {*Asbestos/toxicity ; *Carcinoma ; Carcinoma, Ovarian Epithelial ; Child ; Female ; Humans ; *Mesothelioma/epidemiology ; Middle Aged ; *Occupational Diseases/epidemiology ; *Occupational Exposure/adverse effects ; *Ovarian Neoplasms/epidemiology ; }, abstract = {The International Agency for Research on Cancer established a causal link between asbestos exposure and ovarian cancer. However, the exposure frequency and histological characteristics of asbestos-associated ovarian cancers remain to be investigated in detail. This multicenter case-case study assessed the asbestos exposure in ovarian carcinoma (OC) patients, alongside its association with histological subtype. Women were recruited in four hospitals in Lyon, France. Histological reports were reviewed by a pathologist. Patient and family members' data were collected by phone-based questionnaires. Asbestos exposure was defined as direct (occupational and environmental) and indirect (via parents, partners, and children). An industrial hygienist assessed the probability and level of exposure. The 254 enrolled patients (mean age 60 years) reported having an average of 2.3 different jobs (mean working duration 29 years). The prevalence of direct and indirect asbestos exposure was 13% (mean exposure duration 11 years) and 46%, respectively. High-grade serous carcinoma accounted for 73% of all OCs and 82% of histological subtypes in women with direct exposure. After adjustment on a familial history of OC, no significant associations between asbestos exposure (direct and/or indirect) and high-grade serous carcinoma were found. Women with OC had a high prevalence of asbestos exposure. Establishing risk profiles, as reported here, is important in facilitating compensation for asbestos-related OCs and for the surveillance of women at risk.}, } @article {pmid35559971, year = {2021}, author = {Murphy, F and Dekkers, S and Braakhuis, H and Ma-Hock, L and Johnston, H and Janer, G and di Cristo, L and Sabella, S and Jacobsen, NR and Oomen, AG and Haase, A and Fernandes, T and Stone, V}, title = {An integrated approach to testing and assessment of high aspect ratio nanomaterials and its application for grouping based on a common mesothelioma hazard.}, journal = {NanoImpact}, volume = {22}, number = {}, pages = {100314}, doi = {10.1016/j.impact.2021.100314}, pmid = {35559971}, issn = {2452-0748}, mesh = {*Asbestos/toxicity ; Humans ; *Mesothelioma/chemically induced ; *Mesothelioma, Malignant ; *Nanostructures/adverse effects ; Risk Assessment/methods ; }, abstract = {Here we describe the development of an Integrated Approach to Testing and Assessment (IATA) to support the grouping of different types (nanoforms; NFs) of High Aspect Ratio Nanomaterials (HARNs), based on their potential to cause mesothelioma. Hazards posed by the inhalation of HARNs are of particular concern as they exhibit physical characteristics similar to pathogenic asbestos fibres. The approach for grouping HARNs presented here is part of a framework to provide guidance and tools to group similar NFs and aims to reduce the need to assess toxicity on a case-by-case basis. The approach to grouping is hypothesis-driven, in which the hypothesis is based on scientific evidence linking critical physicochemical descriptors for NFs to defined fate/toxicokinetic and hazard outcomes. The HARN IATA prompts users to address relevant questions (at decision nodes; DNs) regarding the morphology, biopersistence and inflammatory potential of the HARNs under investigation to provide the necessary evidence to accept or reject the grouping hypothesis. Each DN in the IATA is addressed in a tiered manner, using data from simple in vitro or in silico methods in the lowest tier or from in vivo approaches in the highest tier. For these proposed methods we provide justification for the critical descriptors and thresholds that allow grouping decisions to be made. Application of the IATA allows the user to selectively identify HARNs which may pose a mesothelioma hazard, as demonstrated through a literature-based case study. By promoting the use of alternative, non-rodent approaches such as in silico modelling, in vitro and cell-free tests in the initial tiers, the IATA testing strategy streamlines information gathering at all stages of innovation through to regulatory risk assessment while reducing the ethical, time and economic burden of testing.}, } @article {pmid35558518, year = {2022}, author = {Martens, M and Kreidl, F and Ehrhart, F and Jean, D and Mei, M and Mortensen, HM and Nash, A and Nymark, P and Evelo, CT and Cerciello, F}, title = {A Community-Driven, Openly Accessible Molecular Pathway Integrating Knowledge on Malignant Pleural Mesothelioma.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {849640}, pmid = {35558518}, issn = {2234-943X}, abstract = {Malignant pleural mesothelioma (MPM) is a highly aggressive malignancy mainly triggered by exposure to asbestos and characterized by complex biology. A significant body of knowledge has been generated over the decades by the research community which has improved our understanding of the disease toward prevention, diagnostic opportunities and new treatments. Omics technologies are opening for additional levels of information and hypotheses. Given the growing complexity and technological spread of biological knowledge in MPM, there is an increasing need for an integrating tool that may allow scientists to access the information and analyze data in a simple and interactive way. We envisioned that a platform to capture this widespread and fast-growing body of knowledge in a machine-readable and simple visual format together with tools for automated large-scale data analysis could be an important support for the work of the general scientist in MPM and for the community to share, critically discuss, distribute and eventually advance scientific results. Toward this goal, with the support of experts in the field and informed by existing literature, we have developed the first version of a molecular pathway model of MPM in the biological pathway database WikiPathways. This provides a visual and interactive overview of interactions and connections between the most central genes, proteins and molecular pathways known to be involved or altered in MPM. Currently, 455 unique genes and 247 interactions are included, derived after stringent manual curation of an initial 39 literature references. The pathway model provides a directly employable research tool with links to common databases and repositories for the exploration and the analysis of omics data. The resource is publicly available in the WikiPathways database (Wikipathways : WP5087) and continues to be under development and curation by the community, enabling the scientists in MPM to actively participate in the prioritization of shared biological knowledge.}, } @article {pmid35552365, year = {2022}, author = {Mazurek, JM and Blackley, DJ and Weissman, DN}, title = {Malignant Mesothelioma Mortality in Women - United States, 1999-2020.}, journal = {MMWR. Morbidity and mortality weekly report}, volume = {71}, number = {19}, pages = {645-649}, pmid = {35552365}, issn = {1545-861X}, mesh = {*Asbestos/adverse effects ; Data Collection ; Female ; Humans ; Male ; *Mesothelioma/etiology ; *Mesothelioma, Malignant ; *Occupational Exposure/adverse effects ; United States/epidemiology ; }, abstract = {Inhalation of asbestos fibers can cause malignant mesothelioma, a rapidly progressing and lethal cancer of the mesothelium, the thin layer of tissues surrounding internal organs in the chest and abdomen. Patients with malignant mesothelioma have a poor prognosis, with a median survival of 1 year from diagnosis. The estimated median interval from initial occupational asbestos exposure to death is 32 years (range = 13-70 years) (1). Occupational asbestos exposure is most often reported in men working in industries such as construction and manufacturing; however, women are also at risk for exposure to asbestos fibers, and limited data exist on longer-term trends in mesothelioma deaths among women. To characterize deaths associated with mesothelioma and temporal trends in mesothelioma mortality among women in the United States, CDC analyzed annual Multiple Cause of Death records from the National Vital Statistics System for 1999-2020, the most recent years for which complete data are available. The annual number of mesothelioma deaths among women increased significantly, from 489 in 1999 to 614 in 2020; however, the age-adjusted death rate per 1 million women declined significantly, from 4.83 in 1999 to 4.15 in 2020. The largest number of deaths was associated with the health care and social assistance industry (89; 15.7%) and homemaker occupation (129; 22.8%). Efforts to limit exposure to asbestos fibers, including among women, need to be maintained.}, } @article {pmid35547634, year = {2022}, author = {Li, X and Wang, D and Liu, A and Hu, W and Sun, X}, title = {Epidemiological Characteristics of Occupational Cancers Reported - China, 2006-2020.}, journal = {China CDC weekly}, volume = {4}, number = {17}, pages = {370-373}, pmid = {35547634}, issn = {2096-7071}, abstract = {INTRODUCTION: Occupational cancers are a major threat to workers' health in China. The latest version of the Classification and Catalogue of the Occupational Diseases includes 11 occupational cancers. This study analyzed the epidemiological characteristics of occupational cancers in China reported to the National Occupational Disease Reporting System during 2006-2020.

METHODS: Occupational cancers reported during 2016-2020 were obtained from the National Occupational Disease Reporting System. Epidemiological characteristics were analyzed by year, region, industry, gender, age at diagnosis, and exposure duration to occupational hazards.

RESULTS: Overall, a total of 1,116 cases of occupational cancers were reported between 2006 and 2020. The main types reported were leukemia caused by benzene exposure (511, 45.79%), lung cancer caused by coke oven exhaust exposure (266, 23.84%), and lung cancer and mesothelioma caused by asbestos exposure (226, 20.25%). There were 6 provincial-level administrative divisions (PLADs) that had reported over 50 new cases in the last 15 years. Most cases (913, 81.18%) were distributed in the manufacturing industry. There were 870 (77.96%) male cases and 246 (22.04%) female cases. The average age at diagnosis of all reported cases was 51.91±15.85 years, and the median exposure duration to occupational hazards was 12 (5.29-23.25) years.

CONCLUSIONS: There is a large discrepancy between the high morbidity of occupational cancers and a low number of cases diagnosed and reported cases. Occupational cancers in China may be underestimated, and comprehensive measures should be taken to improve the diagnosis and reporting of occupational cancers.}, } @article {pmid35533249, year = {2022}, author = {Anobile, DP and Montenovo, G and Pecoraro, C and Franczak, M and Ait Iddouch, W and Peters, GJ and Riganti, C and Giovannetti, E}, title = {Splicing deregulation, microRNA and notch aberrations: fighting the three-headed dog to overcome drug resistance in malignant mesothelioma.}, journal = {Expert review of clinical pharmacology}, volume = {15}, number = {3}, pages = {305-322}, doi = {10.1080/17512433.2022.2074835}, pmid = {35533249}, issn = {1751-2441}, mesh = {Drug Resistance, Neoplasm/genetics ; Humans ; *Mesothelioma, Malignant/genetics ; *MicroRNAs/genetics ; Neoplasm Recurrence, Local ; Prognosis ; *RNA Splicing/genetics ; *Receptors, Notch/metabolism ; }, abstract = {INTRODUCTION: Malignant mesothelioma (MMe) is an aggressive rare cancer of the mesothelium, associated with asbestos exposure. MMe is currently an incurable disease at all stages mainly due to resistance to treatments. It is therefore necessary to elucidate key mechanisms underlying chemoresistance, in an effort to exploit them as novel therapeutic targets.

AREAS COVERED: Chemoresistance is frequently elicited by microRNA (miRNA) alterations and splicing deregulations. Indeed, several miRNAs, such as miR-29c, have been shown to exert oncogenic or oncosuppressive activity. Alterations in the splicing machinery might also be involved in chemoresistance. Moreover, the Notch signaling pathway, often deregulated in MMe, plays a key role in cancer stem cells formation and self-renewal, leading to drug resistance and relapses.

EXPERT OPINION: The prognosis of MMe in patients varies among different tumors and patient characteristics, and novel biomarkers and therapies are warranted. This work aims at giving an overview of MMe, with a special focus on state-of-the-art treatments and new therapeutic strategies against vulnerabilities emerging from studies on epigenetics factors. Besides, this review is also the first to discuss the interplay between miRNAs and alternative splicing as well as the role of Notch as new promising frontiers to overcome drug resistance in MMe.}, } @article {pmid35524457, year = {2022}, author = {Almeida, GC and Santos, UP and Parente, YDM and Colares, PFB and Mizutani, RF and Bernardi, FDC and Terra, RM and Terra-Filho, M}, title = {Mesothelioma in situ with regressive malignant pleural effusion and an unexpected evolution: A case report.}, journal = {American journal of industrial medicine}, volume = {65}, number = {7}, pages = {620-623}, doi = {10.1002/ajim.23358}, pmid = {35524457}, issn = {1097-0274}, mesh = {Aged ; *Asbestos/toxicity ; Humans ; Male ; *Mesothelioma/etiology ; *Mesothelioma, Malignant ; *Pleural Effusion, Malignant/complications ; *Pleural Neoplasms/etiology ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive neoplasm that originates from hyperplasia and metaplasia of the mesothelial cells that cover the pleural cavity. Previous exposure to asbestos is the main risk factor. Since MPM is often diagnosed at an advanced stage with rapid evolution and resistance to treatment, it is associated with an unfavorable outcome. Mesothelioma in situ (MIS) has been postulated as a preinvasive phase of MPM; however, its diagnostic criteria have been defined only recently. Diagnosis of MIS may represent an opportunity for early therapies with better results, but the optimal approach has not been defined thus far. Here, we report on a case of a 74-year-old man with right-sided pleural effusion and a previous history of occupational exposure to asbestos for 9 years who was diagnosed with MIS after a latency of 36 years. During follow-up, spontaneous disease regression was observed 5 months after the initial diagnosis; however, it recurred in the form of invasive epithelioid MPM. There is a paucity of literature on MIS and its evolution; however, our case provides relevant knowledge of this unusual behavior, which is important to define follow-up and therapeutic strategies for future cases.}, } @article {pmid35501851, year = {2022}, author = {Malakoti, F and Targhazeh, N and Abadifard, E and Zarezadeh, R and Samemaleki, S and Asemi, Z and Younesi, S and Mohammadnejad, R and Hadi Hossini, S and Karimian, A and Alemi, F and Yousefi, B}, title = {DNA repair and damage pathways in mesothelioma development and therapy.}, journal = {Cancer cell international}, volume = {22}, number = {1}, pages = {176}, pmid = {35501851}, issn = {1475-2867}, abstract = {Malignant mesothelioma (MMe) is an aggressive neoplasm that occurs through the transformation of mesothelial cells. Asbestos exposure is the main risk factor for MMe carcinogenesis. Other important etiologies for MMe development include DNA damage, over-activation of survival signaling pathways, and failure of DNA damage response (DDR). In this review article, first, we will describe the most important signaling pathways that contribute to MMe development and their interaction with DDR. Then, the contribution of DDR failure in MMe progression will be discussed. Finally, we will review the latest MMe therapeutic strategies that target the DDR pathway.}, } @article {pmid35497939, year = {2022}, author = {Kambara, T and Amatya, VJ and Kushitani, K and Fujii, Y and Endo, I and Takeshima, Y}, title = {Downregulation of FTL decreases proliferation of malignant mesothelioma cells by inducing G1 cell cycle arrest.}, journal = {Oncology letters}, volume = {23}, number = {6}, pages = {174}, pmid = {35497939}, issn = {1792-1082}, abstract = {Pleural malignant mesothelioma is a malignant tumor with a poor prognosis that is strongly associated with asbestos exposure during its development. Because there is no adequate treatment for malignant mesothelioma, investigation of its molecular mechanism is important. The ferritin light chain (FTL) is a subunit of ferritin, and its high expression in malignant tumors, including malignant mesothelioma, has recently been reported; however, its role in malignant mesothelioma is unclear. The purpose of the present study was to clarify the function of FTL in malignant mesothelioma. The expression levels of FTL in malignant mesothelioma were examined using the Cancer Cell Line Encyclopedia database and our previous data. The short interfering (si)RNA against FTL was transfected into two mesothelioma cell lines, ACC-MESO-1 and CRL-5915, and functional analysis was performed. Expression of p21, p27, cyclin-dependent kinase 2 (CDK2) and phosphorylated retinoblastoma protein (pRb) associated with the cell cycle were examined as candidate genes associated with FTL. The expression levels of the FTL mRNA were higher in malignant mesothelioma compared with other tumors in the Cancer Cell Line Encyclopedia database, and among other genes in our previous study. Reverse transcription-quantitative PCR and western blotting demonstrated suppression of FTL expression in two cell lines transfected with FTL siRNA compared with cells transfected with negative control (NC) siRNA. In the two cell lines transfected with FTL siRNA, proliferation was significantly suppressed, and cell cycle arrest was observed in the G1 phase. The levels of p21 and p27 were increased, while those of CDK2 and pRb were decreased compared with NC. However, no significant differences in invasion and migration ability were revealed between FTL siRNA-transfected cells and NC. In conclusion, FTL may increase the proliferative capacity of malignant mesothelioma cells by affecting p21, p27, CDK2 and pRb, and promoting the cell cycle at the G1 phase.}, } @article {pmid35489694, year = {2022}, author = {Louw, A and Panou, V and Szejniuk, WM and Meristoudis, C and Chai, SM and van Vliet, C and Lee, YCG and Dick, IM and Firth, T and Lynggaard, LA and Asghari, AB and Vyberg, M and Hansen, J and Creaney, J and Røe, OD}, title = {BAP1 Loss by Immunohistochemistry Predicts Improved Survival to First-Line Platinum and Pemetrexed Chemotherapy for Patients With Pleural Mesothelioma: A Validation Study.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {17}, number = {7}, pages = {921-930}, doi = {10.1016/j.jtho.2022.04.008}, pmid = {35489694}, issn = {1556-1380}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Australia/epidemiology ; Humans ; Immunohistochemistry ; *Lung Neoplasms/pathology ; *Mesothelioma/pathology ; *Mesothelioma, Malignant ; Pemetrexed/therapeutic use ; Platinum/therapeutic use ; *Pleural Neoplasms/pathology ; Tumor Suppressor Proteins ; Ubiquitin Thiolesterase ; }, abstract = {INTRODUCTION: Pleural mesothelioma (PM) is an aggressive malignancy with no identified predictive biomarkers. We assessed whether tumor BAP1 status is a predictive biomarker for survival in patients receiving first-line combination platinum and pemetrexed therapy.

METHODS: PM cases (n = 114) from Aalborg, Denmark, were stained for BAP1 on tissue microarrays. Demographic, clinical, and survival data were extracted from registries and medical records. Surgical cases were excluded. BAP1 status was associated with overall survival (OS) by Cox regression and Kaplan-Meier methods. Results were validated in an independent cohort from Perth, Australia (n = 234).

RESULTS: BAP1 loss was found in 62% and 60.3% of all Danish and Australian samples, respectively. BAP1 loss was an independent predictor of OS in multivariate analyses corrected for histological subtype, performance status, age, sex, and treatment (hazard ratio = 2.49, p < 0.001, and 1.48, p = 0.01, respectively). First-line platinum and pemetrexed-treated patients with BAP1 loss had significantly longer median survival than those with retained BAP1 in both the Danish (20.1 versus 7.3 mo, p < 0.001) and Australian cohorts (19.6 versus 11.1 mo, p < 0.01). Survival in patients with BAP1 retained and treated with platinum and pemetrexed was similar as in those with best supportive care. There was a higher OS in patients with best supportive care with BAP1 loss, but it was significant only in the Australian cohort (16.8 versus 8.3 mo, p < 0.01).

CONCLUSIONS: BAP1 is a predictive biomarker for survival after first-line combination platinum and pemetrexed chemotherapy and a potential prognostic marker in PM. BAP1 in tumor is a promising clinical tool for treatment stratification.}, } @article {pmid35472827, year = {2022}, author = {Maghin, F and Antonietti, A and Cerri, N and Lancini, LM and Maccarinelli, A and Manzoni, S and Restori, M and Rota, M and Ruffini, D and Verzeletti, A and Conti, A}, title = {Assessment protocol of mesothelioma and relevance of SEM-EDS analysis through a case studies of legal medicine of Brescia (Italy).}, journal = {Legal medicine (Tokyo, Japan)}, volume = {57}, number = {}, pages = {102076}, doi = {10.1016/j.legalmed.2022.102076}, pmid = {35472827}, issn = {1873-4162}, mesh = {*Asbestos/adverse effects ; Autopsy ; Humans ; Italy ; *Mesothelioma/chemistry/diagnosis/etiology ; *Mesothelioma, Malignant ; *Occupational Diseases/complications ; Retrospective Studies ; }, abstract = {INTRODUCTION: This study evaluates the assessment protocol that allows the correlation between the development of mesothelioma to a specific exposure, with particular focus on investigations with Scanning Electron Microscope with Energy Dispersion Spectroscopy.

METHODS: This retrospective study includes 80 subjects who died from mesothelioma in the period 2001-2019. A judicial autopsy was performed for each case to confirm cause of death and correlate the disease with specific asbestos exposure. In 28 cases investigations were carried out to determine the pulmonary load of the asbestos fibres and corpuscles in the lung tissue through microscopic investigations, in order to confirm the suspicion of occupational exposure.

RESULTS: Our data agree with the scientific literature reported, but it is interesting to underline how the present study uses a different systematic approach than others, which are mainly based on epidemiological and environmental studies without considering the lung content of fibres and corpuscles.

CONCLUSION: It would be desirable that the use of the microscopic analysis was introduced in the evaluation protocol: it should always be carried out if the suspicion of asbestos-related disease is raised and not only as a possible integration to the less expensive anamnestic evaluation, even more so if the work or personal history should be suggestive of exposure to asbestos fibres.}, } @article {pmid35462085, year = {2022}, author = {Carbone, M and Pass, HI and Ak, G and Alexander, HR and Baas, P and Baumann, F and Blakely, AM and Bueno, R and Bzura, A and Cardillo, G and Churpek, JE and Dianzani, I and De Rienzo, A and Emi, M and Emri, S and Felley-Bosco, E and Fennell, DA and Flores, RM and Grosso, F and Hayward, NK and Hesdorffer, M and Hoang, CD and Johansson, PA and Kindler, HL and Kittaneh, M and Krausz, T and Mansfield, A and Metintas, M and Minaai, M and Mutti, L and Nielsen, M and O'Byrne, K and Opitz, I and Pastorino, S and Pentimalli, F and de Perrot, M and Pritchard, A and Ripley, RT and Robinson, B and Rusch, V and Taioli, E and Takinishi, Y and Tanji, M and Tsao, AS and Tuncer, AM and Walpole, S and Wolf, A and Yang, H and Yoshikawa, Y and Zolondick, A and Schrump, DS and Hassan, R}, title = {Medical and Surgical Care of Patients With Mesothelioma and Their Relatives Carrying Germline BAP1 Mutations.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {17}, number = {7}, pages = {873-889}, pmid = {35462085}, issn = {1556-1380}, support = {R01 CA198138/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R01 CA237235/CA/NCI NIH HHS/United States ; U01 CA214195/CA/NCI NIH HHS/United States ; R01 ES030948/ES/NIEHS NIH HHS/United States ; }, mesh = {Genetic Predisposition to Disease ; Germ-Line Mutation ; Humans ; *Lung Neoplasms/diagnosis/genetics/surgery ; *Melanoma/genetics ; *Mesothelioma/diagnosis/genetics/surgery ; *Mesothelioma, Malignant ; Quality of Life ; *Skin Neoplasms/genetics ; Tumor Suppressor Proteins/genetics/metabolism ; Ubiquitin Thiolesterase/genetics/metabolism ; }, abstract = {The most common malignancies that develop in carriers of BAP1 germline mutations include diffuse malignant mesothelioma, uveal and cutaneous melanoma, renal cell carcinoma, and less frequently, breast cancer, several types of skin carcinomas, and other tumor types. Mesotheliomas in these patients are significantly less aggressive, and patients require a multidisciplinary approach that involves genetic counseling, medical genetics, pathology, surgical, medical, and radiation oncology expertise. Some BAP1 carriers have asymptomatic mesothelioma that can be followed by close clinical observation without apparent adverse outcomes: they may survive many years without therapy. Others may grow aggressively but very often respond to therapy. Detecting BAP1 germline mutations has, therefore, substantial medical, social, and economic impact. Close monitoring of these patients and their relatives is expected to result in prolonged life expectancy, improved quality of life, and being cost-effective. The co-authors of this paper are those who have published the vast majority of cases of mesothelioma occurring in patients carrying inactivating germline BAP1 mutations and who have studied the families affected by the BAP1 cancer syndrome for many years. This paper reports our experience. It is intended to be a source of information for all physicians who care for patients carrying germline BAP1 mutations. We discuss the clinical presentation, diagnostic and treatment challenges, and our recommendations of how to best care for these patients and their family members, including the potential economic and psychosocial impact.}, } @article {pmid35461395, year = {2022}, author = {Napoli, F and Rapa, I and Izzo, S and Rigutto, A and Libener, R and Riganti, C and Bironzo, P and Taulli, R and Papotti, M and Volante, M and Scagliotti, G and Righi, L}, title = {Micro-RNA-215 and -375 regulate thymidylate synthase protein expression in pleural mesothelioma and mediate epithelial to mesenchymal transition.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {481}, number = {2}, pages = {233-244}, pmid = {35461395}, issn = {1432-2307}, support = {IG 2019 - ID 23760//Associazione Italiana per la Ricerca sul Cancro/ ; GR-2011-02348356//Regione Piemonte/ ; }, mesh = {Cell Line, Tumor ; *Epithelial-Mesenchymal Transition/genetics ; Gene Expression Regulation, Neoplastic ; Humans ; *Mesothelioma, Malignant/genetics/pathology ; *MicroRNAs/genetics ; *Pleural Neoplasms/genetics/pathology ; *Thymidylate Synthase/genetics/metabolism ; }, abstract = {The standard front-line treatment for pleural mesothelioma (PM) is pemetrexed-based chemotherapy, whose major target is thymidylate synthase (TS). In several cancer models, miR-215 and miR-375 have been shown to target TS, while information on these miRNAs in PM are still limited although suggest their role in epithelial to mesenchymal transition. Seventy-one consecutive PM tissues (4 biphasic, 7 sarcomatoid, and 60 epithelioid types) and 16 commercial and patient-derived PM cell lines were screened for TS, miR-215, and miR-375 expression. REN and 570B cells were selected for miR-215 and miR-375 transient transfections to test TS modulation. ZEB1 protein expression in tumor samples was also tested. Moreover, genetic profile was investigated by means of BAP1 and p53 immunohistochemistry. Expression of both miR-215 and miR-375 was significantly higher in epithelioid histotype. Furthermore, inverse correlation between TS protein and both miR-215 and miR-375 expression was found. Efficiently transfected REN and 570B cell lines overexpressing miR-215 and miR-375 showed decreased TS protein levels. Epithelioid PM with a mesenchymal component highlighted by reticulin stain showed significantly higher TS and ZEB1 protein and lower miRNA expression. A better survival was recorded for BAP1 lost/TS low cases. Our data indicate that miR-215 and miR-375 are involved in TS regulation as well as in epithelial-to-mesenchymal transition in PM.}, } @article {pmid35443624, year = {2022}, author = {Ziółkowska, B and Cybulska-Stopa, B and Papantoniou, D and Suwiński, R}, title = {Systemic treatment in patients with malignant pleural mesothelioma - real life experience.}, journal = {BMC cancer}, volume = {22}, number = {1}, pages = {432}, pmid = {35443624}, issn = {1471-2407}, mesh = {Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Female ; Humans ; *Lung Neoplasms/pathology ; Male ; *Mesothelioma/pathology ; *Mesothelioma, Malignant ; Middle Aged ; Pemetrexed/therapeutic use ; *Pleural Neoplasms ; Retrospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare, aggressive malignancy of the pleural cavity linked to asbestos exposure. The combination of pemetrexed and platinum is a standard first-line therapy for malignant pleural mesothelioma. Despite some progress, almost all MPM patients experience progression after first-line therapy. The second-line treatment is still being under discussion and there are very limited data available on the second-line and subsequent treatments.

METHODS: The retrospective analysis included 57 patients (16 females and 41 males) from two Polish oncological institutions treated for advanced mesothelioma between 2013 and 2019. We analysed the efficacy of first-line and second-line therapy: progression-free survival (PFS), overall survival (OS), overall response rate (ORR).

RESULTS: In the first-line treatment, 55 patients received pemetrexed-based chemotherapy (PBC) and two cisplatin in monotherapy. Patients' characteristics at baseline: median age was 64.2 years, ECOG PS ≤ 1 (86.2%), epithelial histology (85.7%). Median PFS and OS were 7.6 months and 14 months, respectively. Patients with ECOG PS ≤ 1 vs > 1 had a longer median OS (14.8 months vs 9.7 months, p = 0.057). One-year OS and PFS were 60.9% and 32.0%, respectively. Disease control rate (DCR) was 82.5%. Response to first-line therapy: PFS ≥ 6 months and PFS ≥ 12 months had a significant impact on median OS. Twelve patients received second-line therapy (seven PBC and five other cytotoxic single agents: navelbine, gemcitabine, or adriamycin/vincristine/methotrexate triplet). Median PFS and OS were 3.7 months and 7.2 months, respectively. DCR was 83%. One-year OS and PFS were 37% and 16.7%, respectively. In the group receiving PBC, OS was prolonged by 4.5 months compared to the non-PBC group (6.0 months vs 10.5 months, p = 0.47).

CONCLUSION: Patients who benefited from first-line therapy and had prolonged PFS at first-line and achieve PFS longer than 6 months at first-line should be offered second-line treatment. Consideration of retreatment with the same cytotoxic agent could to be a viable option when no other treatment are available.}, } @article {pmid35439870, year = {2022}, author = {Jin, MY and Jiang, ZQ}, title = {[Research progress on the role of lncRNA in the occurrence and development of malignant mesothelioma].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {40}, number = {3}, pages = {231-235}, doi = {10.3760/cma.j.cn121094-20210413-00205}, pmid = {35439870}, issn = {1001-9391}, support = {2019RC142//Zhejiang Medical and Health Science and Technology Program/ ; 11-ZC02//Zhejiang Medical Support Discipline Labor Hygiene/ ; KYYB202113//Basic Scientific Research Projects of Hangzhou Medical College/ ; }, mesh = {*Asbestos ; Epigenesis, Genetic ; Humans ; *Mesothelioma/genetics ; *Mesothelioma, Malignant ; Prognosis ; *RNA, Long Noncoding/genetics ; }, abstract = {Malignant mesothelioma (MM) is a long latency, poor prognosis and asbestos exposure related malignant disease. Long non-coding RNA (lncRNA) is a kind of RNA with a length of more than 200 nucleotides that does not encode protein. It plays an important role in epigenetic regulation, cell cycle regulation and cell differentiation regulation. Recent studies have shown that the abnormal expression or function of lncRNA is closely related to the diagnosis and prognosis of MM. In this paper, the lncRNA research on MM is reviewed to better understand the role of lncRNA in MM.}, } @article {pmid35431929, year = {2022}, author = {Robinson, BWS and Redwood, AJ and Creaney, J}, title = {How Our Continuing Studies of the Pre-clinical Inbred Mouse Models of Mesothelioma Have Influenced the Development of New Therapies.}, journal = {Frontiers in pharmacology}, volume = {13}, number = {}, pages = {858557}, pmid = {35431929}, issn = {1663-9812}, abstract = {Asbestos-induced preclinical mouse models of mesothelioma produce tumors that are very similar to those that develop in humans and thus represent an ideal platform to study this rare, universally fatal tumor type. Our team and a number of other research groups have established such models as a stepping stone to new treatments, including chemotherapy, immunotherapy and other approaches that have been/are being translated into clinical trials. In some cases this work has led to changes in mesothelioma treatment practice and over the last 30 years these models and studies have led to trials which have improved the response rate in mesothelioma from less than 10% to over 50%. Mouse models have had a vital role in that improvement and will continue to play a key role in the future success of mesothelioma immunotherapy. In this review we focus only on these original inbred mouse models, the large number of preclinical studies conducted using them and their contribution to current and future clinical therapy for mesothelioma.}, } @article {pmid35410957, year = {2023}, author = {Dawson, AG and Kutywayo, K and Mohammed, SB and Fennell, DA and Nakas, A}, title = {Cytoreductive surgery with hyperthermic intrathoracic chemotherapy for malignant pleural mesothelioma: a systematic review.}, journal = {Thorax}, volume = {78}, number = {4}, pages = {409-417}, doi = {10.1136/thoraxjnl-2021-218214}, pmid = {35410957}, issn = {1468-3296}, mesh = {Humans ; *Mesothelioma, Malignant ; *Mesothelioma/surgery ; Cisplatin/therapeutic use ; Cytoreduction Surgical Procedures ; *Pleural Neoplasms/drug therapy/surgery ; Combined Modality Therapy ; }, abstract = {INTRODUCTION: Cytoreductive surgery has been used a part of multimodality treatment in patients with malignant pleural mesothelioma (MPM). The residual microscopic disease that remains will lead to disease progression in the majority of patients. Delivery of hyperthermic intrathoracic chemotherapy at the time of surgery has been used to address this microscopic disease, however it's effect and place in the multimodality treatment sphere is unknown. The aim of this systematic review was to assess the effect of surgery and hyperthermic intrathoracic chemotherapy in patients with MPM on overall survival and disease-free interval.

METHODS: Ovid MEDLINE, Embase, Web of Science and the Cochrane Database of Systematic Reviews were searched from database inception through to June 2021. Studies reporting overall survival and/or disease-free interval in patients with MPM undergoing cytoreductive surgery with hyperthermic intrathoracic chemotherapy were considered. Study quality was assessed using the Newcastle-Ottawa Scale. A narrative review was performed.

RESULTS: Fifteen studies were eligible for inclusion comprising 598 patients. Surgery with hyperthermic intrathoracic chemotherapy was associated with a median overall survival and disease-free interval ranging from 11 to 75 months and 7.2 to 57 months, respectively. These appeared to be superior to patients not receiving hyperthermic intrathoracic chemotherapy (overall survival: 5-36 months and disease-free interval: 12.1-21 months). A higher dose of hyperthermic intrathoracic chemotherapy was associated with an improvement in overall survival compared with a lower dose: 18-31 months versus 6-18 months, respectively. The most common morbidity was atrial fibrillation followed by renal complications.

CONCLUSION: Surgery with hyperthermic intrathoracic chemotherapy offers a safe and effective therapy with an improvement in disease-free interval and overall survival, particularly when hyperthermic intrathoracic chemotherapy is administered at a higher dose.

PROSPERO REGISTRATION NUMBER: CRD42019129002.}, } @article {pmid35409711, year = {2022}, author = {Berry, TA and Belluso, E and Vigliaturo, R and Gieré, R and Emmett, EA and Testa, JR and Steinhorn, G and Wallis, SL}, title = {Asbestos and Other Hazardous Fibrous Minerals: Potential Exposure Pathways and Associated Health Risks.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {7}, pages = {}, pmid = {35409711}, issn = {1660-4601}, support = {P30 ES013508/ES/NIEHS NIH HHS/United States ; }, mesh = {*Asbestos/toxicity ; *Asbestosis/epidemiology ; Carcinogens/toxicity ; Humans ; *Mesothelioma/chemically induced/epidemiology ; *Mesothelioma, Malignant ; *Zeolites ; }, abstract = {There are six elongate mineral particles (EMPs) corresponding to specific dimensional and morphological criteria, known as asbestos. Responsible for health issues including asbestosis, and malignant mesothelioma, asbestos has been well researched. Despite this, significant exposure continues to occur throughout the world, potentially affecting 125 million people in the workplace and causing thousands of deaths annually from exposure in homes. However, there are other EMPS, such as fibrous/asbestiform erionite, that are classified as carcinogens and have been linked to cancers in areas where it has been incorporated into local building materials or released into the environment through earthmoving activities. Erionite is a more potent carcinogen than asbestos but as it is seldom used for commercial purposes, exposure pathways have been less well studied. Despite the apparent similarities between asbestos and fibrous erionite, their health risks and exposure pathways are quite different. This article examines the hazards presented by EMPs with a particular focus on fibrous erionite. It includes a discussion of the global locations of erionite and similar hazardous minerals, a comparison of the multiple exposure pathways for asbestos and fibrous erionite, a brief discussion of the confusing nomenclature associated with EMPs, and considerations of increasing global mesothelioma cases.}, } @article {pmid35409322, year = {2022}, author = {Henzi, T and Diep, KL and Oberson, A and Salicio, V and Bochet, CG and Schwaller, B}, title = {Forchlorfenuron and Novel Analogs Cause Cytotoxic Effects in Untreated and Cisplatin-Resistant Malignant Mesothelioma-Derived Cells.}, journal = {International journal of molecular sciences}, volume = {23}, number = {7}, pages = {}, pmid = {35409322}, issn = {1422-0067}, mesh = {Animals ; *Antineoplastic Agents/pharmacology ; Cell Line, Tumor ; Cisplatin/metabolism/pharmacology ; Halogens/metabolism ; *Mesothelioma/drug therapy ; *Mesothelioma, Malignant ; Mice ; Phenylurea Compounds/pharmacology ; Pyridines ; Septins/metabolism ; }, abstract = {Malignant mesothelioma (MM) is a currently incurable, aggressive cancer derived from mesothelial cells, most often resulting from asbestos exposure. The current first-line treatment in unresectable MM is cisplatin/pemetrexed, which shows very little long-term effectiveness, necessitating research for novel therapeutic interventions. The existing chemotherapies often act on the cytoskeleton, including actin filaments and microtubules, but recent advances indicate the 'fourth' form consisting of the family of septins, representing a novel target. The septin inhibitor forchlorfenuron (FCF) and FCF analogs inhibit MM cell growth in vitro, but at concentrations which are too high for clinical applications. Based on the reported requirement of the chloride group in the 2-position of the pyridine ring of FCF for MM cell growth inhibition and cytotoxicity, we systematically investigated the importance (cell growth-inhibiting capacity) of the halogen atoms fluorine, chlorine, bromine and iodine in the 2- or 3-position of the pyridine ring. The MM cell lines ZL55, MSTO-211H, and SPC212, and-as a control-immortalized Met-5A mesothelial cells were used. The potency of the various halogen substitutions in FCF was mostly correlated with the atom size (covalent radius); the small fluoride analogs showed the least effect, while the largest one (iodide) most strongly decreased the MTT signals, in particular in MM cells derived from epithelioid MM. In the latter, the strongest effects in vitro were exerted by the 2-iodo and, unexpectedly, the 2-trifluoromethyl (2-CF3) FCF analogs, which were further tested in vivo in mice. However, FCF-2-I and, more strongly, FCF-2-CF3 caused rapidly occurring strong symptoms of systemic toxicity at doses lower than those previously obtained with FCF. Thus, we investigated the effectiveness of FCF (and selected analogs) in vitro in MM cells which were first exposed to cisplatin. The slowly appearing population of cisplatin-resistant cells was still susceptible to the growth-inhibiting/cytotoxic effect of FCF and its analogs, indicating that cisplatin and FCF target non-converging pathways in MM cells. Thus, a combination therapy of cisplatin and FCF (analogs) might represent a new avenue for the treatment of repopulating chemo-resistant MM cells in this currently untreatable cancer.}, } @article {pmid35402250, year = {2022}, author = {Tilsed, CM and Casey, TH and de Jong, E and Bosco, A and Zemek, RM and Salmons, J and Wan, G and Millward, MJ and Nowak, AK and Lake, RA and Lesterhuis, WJ}, title = {Retinoic Acid Induces an IFN-Driven Inflammatory Tumour Microenvironment, Sensitizing to Immune Checkpoint Therapy.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {849793}, pmid = {35402250}, issn = {2234-943X}, abstract = {With immune checkpoint therapy (ICT) having reshaped the treatment of many cancers, the next frontier is to identify and develop novel combination therapies to improve efficacy. Previously, we and others identified beneficial immunological effects of the vitamin A derivative tretinoin on anti-tumour immunity. Although it is known that tretinoin preferentially depletes myeloid derived suppressor cells in blood, little is known about the effects of tretinoin on the tumour microenvironment, hampering the rational design of clinical trials using tretinoin in combination with ICT. Here, we aimed to identify how tretinoin changed the tumour microenvironment in mouse tumour models, using flow cytometry and RNAseq, and we sought to use that information to establish optimal dosing and scheduling of tretinoin in combination with several ICT antibodies in multiple cancer models. We found that tretinoin rapidly induced an interferon dominated inflammatory tumour microenvironment, characterised by increased CD8+ T cell infiltration. This phenotype completely overlapped with the phenotype that was induced by ICT itself, and we confirmed that the combination further amplified this inflammatory milieu. The addition of tretinoin significantly improved the efficacy of anti-CTLA4/anti-PD-L1 combination therapy, and staggered scheduling was more efficacious than concomitant scheduling, in a dose-dependent manner. The positive effects of tretinoin could be extended to ICT antibodies targeting OX40, GITR and CTLA4 monotherapy in multiple cancer models. These data show that tretinoin induces an interferon driven, CD8+ T cell tumour microenvironment that is responsive to ICT.}, } @article {pmid35394203, year = {2022}, author = {Nakashima, K and Sakai, Y and Hoshino, H and Umeda, Y and Kawashima, H and Sekido, Y and Ishizuka, T and Kobayashi, M}, title = {Sulfated Glycans Recognized by S1 Monoclonal Antibody can Serve as a Diagnostic Marker for Malignant Pleural Mesothelioma.}, journal = {Lung}, volume = {200}, number = {3}, pages = {339-346}, pmid = {35394203}, issn = {1432-1750}, mesh = {*Adenocarcinoma of Lung/diagnosis ; Antibodies, Monoclonal ; Humans ; *Lung Neoplasms/diagnosis ; *Mesothelioma/diagnosis/pathology ; *Mesothelioma, Malignant ; *Pleural Neoplasms/diagnosis/pathology ; Polysaccharides ; Sulfates ; }, abstract = {PURPOSE: Malignant pleural mesothelioma (MPM) is a malignant neoplasm of the pleura caused by asbestos exposure. For diagnosis of MPM, immunohistochemistry using multiple markers is recommended to rule out differential diagnoses, such as pulmonary adenocarcinoma. However, the specificity of currently used markers is not fully satisfactory. We previously developed a monoclonal antibody named S1, which recognizes 6-sulfo sialyl Lewis x, an L-selectin ligand expressed on high endothelial venules. During the screening process, we discovered that this antibody stained normal pleural mesothelium. This finding prompted us to hypothesize that the epitope recognized by S1 might serve as a new diagnostic marker for MPM.

METHODS: To test this hypothesis, we immunostained human MPM (n = 22) and lung adenocarcinoma (n = 25) tissues using S1 antibody.

RESULTS: 77.3% of MPM were S1 positive, and if limited to epithelioid type, the positivity rate was 100%, while that of lung adenocarcinoma was only 36.0%. Statistical analysis revealed a significant difference in the S1 positivity rate between each disease. Furthermore, immunohistochemistry using a series of anti-carbohydrate antibodies combined with glycosidase digestion revealed the structure of sulfated glycans expressed in MPM to be 6-sulfo sialyl N-acetyllactosamine attached to core 2-branched O-glycans.

CONCLUSION: We propose that the S1 glycoepitope could serve as a new diagnostic marker for MPM.}, } @article {pmid35378379, year = {2022}, author = {Cameron, JK and Aitken, J and Reid, A and Mengersen, K and Cramb, S and Preston, P and Armstrong, B and Baade, P}, title = {Geographic distribution of malignant mesothelioma incidence and survival in Australia.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {167}, number = {}, pages = {17-24}, doi = {10.1016/j.lungcan.2022.03.017}, pmid = {35378379}, issn = {1872-8332}, mesh = {*Asbestos ; Australia/epidemiology ; Bayes Theorem ; Humans ; Incidence ; *Lung Neoplasms/epidemiology/etiology ; *Mesothelioma ; *Mesothelioma, Malignant ; *Occupational Exposure ; }, abstract = {OBJECTIVES: To understand the geographic distribution of and area-level factors associated with malignant mesothelioma incidence and survival in Australia.

MATERIALS AND METHODS: Generalised linear models and Bayesian spatial models were fitted using population registry data. Area-level covariates were socioeconomic quintile, remoteness category and state or territory. The maximised excess events test was used to test for spatial heterogeneity.

RESULTS: There was strong evidence of spatial differences in standardised incidence rates for malignant mesothelioma but survival was uniformly poor. Incidence rates varied by state or territory and were lower in remote areas. Patterns in the geographic distribution of modelled incidence counts for malignant mesothelioma differed substantially from patterns of standardised incidence rates.

CONCLUSIONS: Geographic variation in the modelled incidence counts of malignant mesothelioma demonstrates varying demand for diagnostic and management services. The long latency period for this cancer coupled with migration complicates any associations with patterns of exposure, however some of the geographic distribution of diagnoses can be explained by the location of historical mines and asbestos-related industries.}, } @article {pmid35367351, year = {2022}, author = {Laaksonen, S and Kettunen, E and Sutinen, E and Ilonen, I and Vehmas, T and Törmäkangas, T and Räsänen, J and Wolff, H and Myllärniemi, M}, title = {Pulmonary Asbestos Fiber Burden Is Related to Patient Survival in Malignant Pleural Mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {17}, number = {8}, pages = {1032-1041}, doi = {10.1016/j.jtho.2022.03.012}, pmid = {35367351}, issn = {1556-1380}, mesh = {*Asbestos/adverse effects ; Humans ; Lung/pathology ; *Lung Neoplasms/pathology ; *Mesothelioma/complications ; *Mesothelioma, Malignant ; *Occupational Exposure/adverse effects ; *Pleural Neoplasms/pathology ; Retrospective Studies ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is associated with poor prognosis and is strongly associated with occupational asbestos exposure. Given the importance of asbestos exposure in MPM pathogenesis, we retrospectively analyzed the types and concentrations of asbestos fibers within the lung tissues of patients with MPM and investigated their effects on all-cause mortality.

METHODS: We formed a national data set of patients with MPM identified from the Finnish Cancer Registry and Statistics Finland. These data were merged with pulmonary asbestos fiber analysis results received from the Finnish Institute of Occupational Health.

RESULTS: We identified 590 patients with MPM who underwent pulmonary asbestos fiber analysis. The median asbestos concentration within dry lung tissue was 3.20 million fibers/gram (range: 0 - 1700 million fibers/gram). Crocidolite and anthophyllite were the most prevalent asbestos fiber types detected in lung tissue. The multivariable risk of death analyses, where changes over time were accounted for, revealed that total asbestos fiber concentration was associated with increased mortality. Nevertheless, no difference in mortality was noted between different fiber types.

CONCLUSIONS: Our study revealed that pulmonary fiber concentrations correlated with the manner of asbestos usage. Anthophyllite was identified as the sole fiber in a sizable proportion of cases, supporting its independent role in the pathogenesis of MPM. Our findings suggest that asbestos fiber burden, but not fiber type, may have an impact on the prognosis of MPM.}, } @article {pmid35360426, year = {2022}, author = {Idkedek, M and Tahayneh, KS and Abu-Akar, F and Bakri, IA}, title = {Case Report and Review of Literature: Familial Malignant Pleural Mesothelioma in a 39 Years Old Patient With an Inconclusive [18]F-FDG PET/CT Result.}, journal = {Frontiers in surgery}, volume = {9}, number = {}, pages = {819596}, pmid = {35360426}, issn = {2296-875X}, abstract = {Malignant pleural mesothelioma (MPM) is a rare yet aggressive neoplasm that was linked only to asbestos exposure for decades, although familial clusters were diagnosed with MPM without a known history of asbestos exposure most likely due to genetic susceptibility. Here, we describe a case of familial malignant mesothelioma in a 39 years old patient with a confirmed BAP1 mutation in addition to a known family history with the same mutation. The patient presented with progressive shortness of breath and recurrent pleural effusions and diagnosis was made through biopsies taken during uniportal Video-Assisted Thoracoscopic Surgery. After the inconclusive result of [18]F-FDG PET/CT scan, subxiphoid uniportal Video-Assisted Thoracoscopic Surgery left pleural and laparoscopic peritoneal biopsies were obtained for staging and evaluating contralateral lung and peritoneal cavity. Finally, two important educational values should be acquired from this case: genetic predisposition and BAP1 tumor suppressor gene mutation might affect the age of presentation and overall prognosis of the disease. Also, [18]F-FDG PET/CT scan may not be the best modality for staging and confirming the diagnosis of malignant pleural mesothelioma.}, } @article {pmid35358455, year = {2022}, author = {Kindler, HL and Novello, S and Bearz, A and Ceresoli, GL and Aerts, JGJV and Spicer, J and Taylor, P and Nackaerts, K and Greystoke, A and Jennens, R and Calabrò, L and Burgers, JA and Santoro, A and Cedrés, S and Serwatowski, P and Ponce, S and Van Meerbeeck, JP and Nowak, AK and Blumenschein, G and Siegel, JM and Kasten, L and Köchert, K and Walter, AO and Childs, BH and Elbi, C and Hassan, R and Fennell, DA}, title = {Anetumab ravtansine versus vinorelbine in patients with relapsed, mesothelin-positive malignant pleural mesothelioma (ARCS-M): a randomised, open-label phase 2 trial.}, journal = {The Lancet. Oncology}, volume = {23}, number = {4}, pages = {540-552}, pmid = {35358455}, issn = {1474-5488}, support = {ZID BC011540/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Humans ; Arthrogryposis ; *Immunoconjugates/adverse effects ; Maytansine/analogs & derivatives ; Mesothelin ; *Mesothelioma, Malignant/drug therapy ; Neoplasm Recurrence, Local/pathology ; Vinorelbine/adverse effects ; }, abstract = {BACKGROUND: Few treatment options exist for second-line treatment of malignant pleural mesothelioma. We aimed to assess the antibody-drug conjugate anetumab ravtansine versus vinorelbine in patients with unresectable locally advanced or metastatic disease overexpressing mesothelin who had progressed on first-line platinum-pemetrexed chemotherapy with or without bevacizumab.

METHODS: In this phase 2, randomised, open-label study, done at 76 hospitals in 14 countries, we enrolled adults (aged ≥18 years) with unresectable locally advanced or metastatic malignant pleural mesothelioma, an Eastern Cooperative Oncology Group performance status of 0-1, and who had progressed on first-line platinum-pemetrexed chemotherapy with or without bevacizumab. Participants were prospectively screened for mesothelin overexpression (defined as 2+ or 3+ mesothelin membrane staining intensity on at least 30% of viable tumour cells by immunohistochemistry) and were randomly assigned (2:1), using an interactive voice and web response system provided by the sponsor, to receive intravenous anetumab ravtansine (6·5 mg/kg on day 1 of each 21-day cycle) or intravenous vinorelbine (30 mg/m[2] once every week) until progression, toxicity, or death. The primary endpoint was progression-free survival according to blinded central radiology review, assessed in the intention-to-treat population, with safety assessed in all participants who received any study treatment. This study is registered with ClinicalTrials.gov, NCT02610140, and is now completed.

FINDINGS: Between Dec 3, 2015, and May 31, 2017, 589 patients were enrolled and 248 mesothelin-overexpressing patients were randomly allocated to the two treatment groups (166 patients were randomly assigned to receive anetumab ravtansine and 82 patients were randomly assigned to receive vinorelbine). 105 (63%) of 166 patients treated with anetumab ravtansine (median follow-up 4·0 months [IQR 1·4-5·5]) versus 43 (52%) of 82 patients treated with vinorelbine (3·9 months [1·4-5·4]) had disease progression or died (median progression-free survival 4·3 months [95% CI 4·1-5·2] vs 4·5 months [4·1-5·8]; hazard ratio 1·22 [0·85-1·74]; log-rank p=0·86). The most common grade 3 or worse adverse events were neutropenia (one [1%] of 163 patients for anetumab ravtansine vs 28 [39%] of 72 patients for vinorelbine), pneumonia (seven [4%] vs five [7%]), neutrophil count decrease (two [1%] vs 12 [17%]), and dyspnoea (nine [6%] vs three [4%]). Serious drug-related treatment-emergent adverse events occurred in 12 (7%) patients treated with anetumab ravtansine and 11 (15%) patients treated with vinorelbine. Ten (6%) treatment-emergent deaths occurred with anetumab ravtansine: pneumonia (three [2%]), dyspnoea (two [1%]), sepsis (two [1%]), atrial fibrillation (one [1%]), physical deterioration (one [1%]), hepatic failure (one [1%]), mesothelioma (one [1%]), and renal failure (one [1%]; one patient had 3 events). One (1%) treatment-emergent death occurred in the vinorelbine group (pneumonia).

INTERPRETATION: Anetumab ravtansine showed a manageable safety profile and was not superior to vinorelbine. Further studies are needed to define active treatments in relapsed mesothelin-expressing malignant pleural mesothelioma.

FUNDING: Bayer Healthcare Pharmaceuticals.}, } @article {pmid35341441, year = {2022}, author = {Ierardi, AM and Best, EA and Marsh, GM}, title = {Updated Italian cohort data continues to confirm lack of mesothelioma risk in pooled cohort of international cosmetic talc miners and millers.}, journal = {Inhalation toxicology}, volume = {34}, number = {5-6}, pages = {135-144}, doi = {10.1080/08958378.2022.2053251}, pmid = {35341441}, issn = {1091-7691}, mesh = {Cohort Studies ; Cosmetics ; *Extraction and Processing Industry ; Humans ; Italy/epidemiology ; *Mesothelioma/epidemiology ; Mining ; *Occupational Diseases/epidemiology ; Risk Assessment ; *Talc/toxicity ; }, abstract = {OBJECTIVES: To assess potential mesothelioma risk following inhalation of cosmetic talc, we updated previous iterations of a pooled cohort analysis, post-study statistical power analysis, and confidence interval function analysis for a pooled cohort of international cosmetic talc miners/millers given new Italian cohort data.

METHODS: Five cohorts of cosmetic talc miners/millers were pooled. Expected numbers of mesotheliomas for each cohort were reported by the original authors. We based our post-study statistical power analysis on an a priori one-sided significance level of 0.05, and exact Poisson and approximate distribution probabilities. To evaluate the confidence interval function for the observed pooled mesothelioma standardized mortality ratios (SMRs), we calculated the probability for the upper 100(1-2α)% confidence limit that equals various SMRs of interest.

RESULTS: The pooled cohorts generated a total observation time of 135,524.38 person-years. Overall, 4.14 mesotheliomas were expected (mid-value estimate), though only one case of mesothelioma has been confirmed in the pooled cohort to date. We calculated 71% and 87% post-study power to detect a 2.5-fold or greater and a 3.0-fold or greater increase in mesothelioma, respectively. Our complimentary confidence interval function analysis demonstrated that the probability that the true mesothelioma SMR for the pooled cohort was at or above 2.0 or at or above 3.0 was 0.00235 and 0.00005, respectively.

CONCLUSIONS: Based on the updated results of our various analyses, the current epidemiological evidence from cosmetic talc miner/miller cohort studies continues to not support the hypothesis that the inhalation of cosmetic talc is associated with an increased risk of mesothelioma.}, } @article {pmid35339776, year = {2022}, author = {Ejegi-Memeh, S and Sherborne, V and Harrison, M and Taylor, B and Senek, M and Tod, A and Gardiner, C}, title = {Patients' and informal carers' experience of living with mesothelioma: A systematic rapid review and synthesis of the literature.}, journal = {European journal of oncology nursing : the official journal of European Oncology Nursing Society}, volume = {58}, number = {}, pages = {102122}, doi = {10.1016/j.ejon.2022.102122}, pmid = {35339776}, issn = {1532-2122}, mesh = {Adaptation, Psychological ; *Asbestos ; Caregivers/psychology ; Health Personnel ; Humans ; *Mesothelioma/therapy ; Qualitative Research ; }, abstract = {PURPOSE: Mesothelioma is a rare and incurable cancer linked to asbestos exposure. It primarily affects the pleura. This systematic rapid review aimed to identify what is known about the experience of living with mesothelioma, from the perspective of patients and their informal carers.

METHODS: Medline, PsycInfo, Scopus and the Cumulative Index to Nursing and Allied Health Literature were searched for empirical studies published between December 2008 and October 2020. Google Scholar was searched. The inclusion criteria stated that studies were peer-reviewed, reported the experience of living with mesothelioma from the perspective of patients and carers and written in English. The Mixed-Methods Appraisal Tool was used to assess quality. The review protocol is registered on PROSPERO: CRD42020204726.

RESULTS: Twenty-five studies met the inclusion criteria. Following data extraction, a narrative synthesis identified three themes: the impact on the individual; the impact on informal carers and relationships; and interactions with professionals and systems. The physical and psychological symptom burden of mesothelioma on patients' lives was reported as high. Both the qualitative and quantitative literature highlighted that patients and carers may have different needs throughout the mesothelioma journey. Differences included psychological experiences and preferences regarding the timing of information and support provision. Patients and carers expected their health care professionals to be knowledgeable about mesothelioma or refer to those who were. Health care professionals that were compassionate, honest and supportive also positively influenced the experience of patients and carers living with mesothelioma. A lack of communication or misinformation was damaging to the patient-healthcare professional relationship. Continuity of care, coordinated care and good communication between treatment centres were widely reported as important in the literature. Fragmented care was identified as detrimental to the patient experience, increasing anxiety in patients. However, relationships with professionals were not only important in terms of co-ordinating care. There was also evidence that good relationships with healthcare professionals were beneficial to coping with the mesothelioma diagnosis.

CONCLUSION: The volume of mesothelioma experience research has grown over the past decade. This has led to our growing understanding of the complex needs and experiences of mesothelioma patients and carers. However, this review identified several evidence gaps.}, } @article {pmid35329341, year = {2022}, author = {Saito, CA and Bussacos, MA and Salvi, L and Mensi, C and Consonni, D and Fernandes, FT and Campos, F and Cavalcante, F and Algranti, E}, title = {Sex-Specific Mortality from Asbestos-Related Diseases, Lung and Ovarian Cancer in Municipalities with High Asbestos Consumption, Brazil, 2000-2017.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {6}, pages = {}, pmid = {35329341}, issn = {1660-4601}, mesh = {Adult ; *Asbestos/toxicity ; *Asbestosis ; Brazil/epidemiology ; Carcinoma, Ovarian Epithelial ; Cities ; Female ; Humans ; Italy ; Lung ; *Lung Neoplasms ; Male ; *Mesothelioma ; *Occupational Exposure ; *Ovarian Neoplasms ; }, abstract = {The aim of this study is to compare the mortality rates for typical asbestos-related diseases (ARD-T: mesothelioma, asbestosis, and pleural plaques) and for lung and ovarian cancer in Brazilian municipalities where asbestos mines and asbestos-cement plants had been operating (areas with high asbestos consumption, H-ASB) compared with in other municipalities. The death records for adults aged 30+ years were retrieved from multiple health information systems. In the 2000-2017 time period, age-standardized mortality rates (standard: Brazil 2010) and standardized rate ratios (SRR; H-ASB vs. others) were estimated. The SRRs for ARD-T were 2.56 for men (257 deaths in H-ASB municipalities) and 1.19 for women (136 deaths). For lung cancer, the SRRs were 1.33 for men (32,604 deaths) and 1.19 for women (20,735 deaths). The SRR for ovarian cancer was 1.34 (8446 deaths). Except for ARD-T and lung cancer in women, the SRRs were higher in municipalities that began using asbestos before 1970 than in municipalities that began utilizing asbestos from 1970 onwards. In conclusion, the mortality rates for ARD-T, and lung and ovarian cancer in municipalities with a history of asbestos mining and asbestos-cement production exceed those of the whole country. Caution is needed when interpreting the results of this ecological study. Analytical studies are necessary to document the impact of asbestos exposure on health, particularly in the future given the long latency of asbestos-related cancers.}, } @article {pmid35329152, year = {2022}, author = {Stoppa, G and Mensi, C and Fazzo, L and Minelli, G and Manno, V and Consonni, D and Biggeri, A and Catelan, D}, title = {Spatial Analysis of Shared Risk Factors between Pleural and Ovarian Cancer Mortality in Lombardy (Italy).}, journal = {International journal of environmental research and public health}, volume = {19}, number = {6}, pages = {}, pmid = {35329152}, issn = {1660-4601}, mesh = {*Asbestos/adverse effects ; Bayes Theorem ; Carcinoma, Ovarian Epithelial ; Female ; Humans ; Italy/epidemiology ; *Mesothelioma/epidemiology ; *Occupational Exposure/adverse effects ; *Ovarian Neoplasms/epidemiology ; *Pleural Neoplasms/complications/epidemiology ; Risk Factors ; Spatial Analysis ; }, abstract = {BACKGROUND: Asbestos exposure is a recognized risk factor for ovarian cancer and malignant mesothelioma. There are reports in the literature of geographical ecological associations between the occurrence of these two diseases. Our aim was to further explore this association by applying advanced Bayesian techniques to a large population (10 million people).

METHODS: We specified a series of Bayesian hierarchical shared models to the bivariate spatial distribution of ovarian and pleural cancer mortality by municipality in the Lombardy Region (Italy) in 2000-2018.

RESULTS: Pleural cancer showed a strongly clustered spatial distribution, while ovarian cancer showed a less structured spatial pattern. The most supported Bayesian models by predictive accuracy (widely applicable or Watanabe-Akaike information criterion, WAIC) provided evidence of a shared component between the two diseases. Among five municipalities with significant high standardized mortality ratios of ovarian cancer, three also had high pleural cancer rates. Wide uncertainty was present when addressing the risk of ovarian cancer associated with pleural cancer in areas at low background risk of ovarian cancer.

CONCLUSIONS: We found evidence of a shared risk factor between ovarian and pleural cancer at the small geographical level. The impact of the shared risk factor can be relevant and can go unnoticed when the prevalence of other risk factors for ovarian cancer is low. Bayesian modelling provides useful information to tailor epidemiological surveillance.}, } @article {pmid35329075, year = {2022}, author = {Spinazzè, A and Consonni, D and Borghi, F and Rovelli, S and Cattaneo, A and Zellino, C and Dallari, B and Pesatori, AC and Kromhout, H and Peters, S and Riboldi, L and Cavallo, DM and Mensi, C}, title = {Asbestos Exposure in Patients with Malignant Pleural Mesothelioma included in the PRIMATE Study, Lombardy, Italy.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {6}, pages = {}, pmid = {35329075}, issn = {1660-4601}, mesh = {Animals ; *Asbestos/adverse effects ; Female ; Humans ; Italy/epidemiology ; Male ; *Mesothelioma/chemically induced/epidemiology ; *Mesothelioma, Malignant ; *Occupational Exposure/adverse effects ; Primates ; Surveys and Questionnaires ; }, abstract = {The PRIMATE study is an Italian translational research project, which aims to identify personalized biomarkers associated with clinical characteristics of malignant pleural mesothelioma (MPM). For this purpose, characteristics of MPM patients with different degrees of asbestos exposure will be compared to identify somatic mutations, germline polymorphism, and blood inflammatory biomarkers. In this framework, we assessed exposure to asbestos for 562 cases of MPM extracted from the Lombardy region Mesothelioma Registry (RML), for which a complete interview based on a standardized national questionnaire and histopathological specimens were available. Exposure assessment was performed: (1) through experts' evaluation (considered as the gold standard for the purpose of this study), according to the guidelines of the Italian National Mesothelioma Registry (ReNaM) and (2) using a job-exposure matrix (SYN-JEM) to obtain qualitative (ever/never) and quantitative estimates of occupational asbestos exposure (cumulative exposure expressed in fibers per mL (f/mL)). The performance of SYN-JEM was evaluated against the experts' evaluation. According to experts' evaluation, occupational asbestos exposure was recognized in 73.6% of men and 23.6% of women; furthermore, 29 men (7.8%) and 70 women (36.9%) had non-occupational exposure to asbestos. When applying SYN-JEM, 225 men (60.5%) and 25 women (13.2%) were classified as occupationally exposed, with a median cumulative exposure higher for men (1.7 f/mL-years) than for women (1.2 f/mL-years). The concordance between the two methods (Cohen's kappa) for occupational exposure assessment was 0.46 overall (0.41 in men, and 0.07 in women). Sensitivity was higher in men (0.73) than in women (0.18), while specificity was higher in women (0.88) than in men (0.74). Overall, both methods can be used to reconstruct past occupational exposure to asbestos, each with its own advantages and limitations.}, } @article {pmid35328844, year = {2022}, author = {Anaya-Aguilar, C and Bravo, M and Magan-Fernandez, A and Del Castillo-Salmerón, R and Rodríguez-Archilla, A and Montero, J and Rosel, E and Puche, P and Anaya-Aguilar, R}, title = {Prevention of Occupational Hazards Due to Asbestos Exposure in Dentistry. A Proposal from a Panel of Experts.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {6}, pages = {}, pmid = {35328844}, issn = {1660-4601}, mesh = {*Asbestos ; Dentistry ; Humans ; *Lung Neoplasms ; *Mesothelioma/etiology ; *Occupational Exposure/prevention & control ; }, abstract = {Asbestos in all its forms is a Group 1 material agent with proven carcinogenic effects in the human being since 1977. Exposure to asbestos can be considered unsafe. The use of asbestos in the field of dentistry had a common use in the manufacture of dental prostheses in the 1960s and 1970s. Taking into account the long induction period of this agent and the plausibility for being a risk factor in dentistry, the objective of this study is to propose a plan for the prevention of occupational risks due to asbestos exposure in dentistry by means of the contribution of a panel of experts. An Expert Panel (EP) approach was used in which a group of nine experts identified and documented the use of asbestos in the dental profession. EP was created and followed the protocol in accordance with the EuropeAid Assessment Guidelines. As a result of this study, EP documented the common use and sources of asbestos in dentistry in prosthetic materials, dental dressings, and in the coating of casting cylinders. EP also created a consensus document on the priority measures for the Plan for the Prevention of Risks from Asbestos in Dentistry, based on previous reports from the European Commission Senior Labour Inspectors' Committee. The document concluded that obtainment of information, receiving specific training on the subject and performing epidemiological studies, and the proper risk assessments were the priority measures to adopt.}, } @article {pmid35327475, year = {2022}, author = {Rovers, S and Janssens, A and Raskin, J and Pauwels, P and van Meerbeeck, JP and Smits, E and Marcq, E}, title = {Recent Advances of Immune Checkpoint Inhibition and Potential for (Combined) TIGIT Blockade as a New Strategy for Malignant Pleural Mesothelioma.}, journal = {Biomedicines}, volume = {10}, number = {3}, pages = {}, pmid = {35327475}, issn = {2227-9059}, support = {FFB210293//BOF research fund, University of Antwerp/ ; }, abstract = {Malignant pleural mesothelioma (MPM) is a fatal cancer type that affects the membranes lining the lungs, and is causally associated with asbestos exposure. Until recently, the first-line treatment consisted of a combination of chemotherapeutics that only had a limited impact on survival, and had not been improved in decades. With the recent approval of combined immune checkpoint inhibition for MPM, promising new immunotherapeutic strategies are now emerging for this disease. In this review, we describe the current preclinical and clinical evidence of various immune checkpoint inhibitors in MPM. We will consider the advantages of combined immune checkpoint blockade in comparison with single agent checkpoint inhibitor drugs. Furthermore, recent evidence suggests a role for T cell immunoglobulin and ITIM domain (TIGIT), an inhibitory immunoreceptor, as a novel target for immunotherapy. As this novel immune checkpoint remains largely unexplored in mesothelioma, we will discuss the potential of TIGIT blockade as an alternative therapeutic approach for MPM. This review will emphasize the necessity for new and improved treatments for MPM, while highlighting the recent advances and future perspectives of combined immune checkpoint blockade, particularly aimed at PD-L1 and TIGIT.}, } @article {pmid35270479, year = {2022}, author = {Nishida, C and Yatera, K}, title = {The Impact of Ambient Environmental and Occupational Pollution on Respiratory Diseases.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {5}, pages = {}, pmid = {35270479}, issn = {1660-4601}, mesh = {*Air Pollutants, Occupational ; *Air Pollution/adverse effects ; *COVID-19/epidemiology ; Child ; Humans ; *Respiration Disorders ; SARS-CoV-2 ; }, abstract = {Ambient pollutants and occupational pollutants may cause and exacerbate various lung and respiratory diseases. This review describes lung and respiratory diseases in relation to ambient pollutants, particularly particulate matter (PM2.5), and occupational air pollutants, excluding communicable diseases and indoor pollutants, including tobacco smoke exposure. PM2.5 produced by combustion is an important ambient pollutant. PM2.5 can cause asthma attacks and exacerbations of chronic obstructive pulmonary disease in the short term. Further, it not only carries a risk of lung cancer and death, but also hinders the development of lung function in children in the long term. It has recently been suggested that air pollution, such as PM2.5, is a risk factor for severe coronavirus disease (COVID-19). Asbestos, which causes asbestosis, lung cancer, and malignant mesothelioma, and crystalline silica, which cause silicosis, are well-known traditional occupational pollutants leading to pneumoconiosis. While work-related asthma (WRA) is the most common occupational lung disease in recent years, many different agents cause WRA, including natural and synthetic chemicals and irritant gases. Primary preventive interventions that increase awareness of pollutants and reduce the development and exacerbation of diseases caused by air pollutants are paramount to addressing ambient and occupational pollution.}, } @article {pmid35269773, year = {2022}, author = {Serio, G and Pezzuto, F and Fortarezza, F and Marzullo, A and Delfino, MC and d'Amati, A and Romano, DE and Maniglio, S and Caporusso, C and Lettini, T and Cavone, D and Vimercati, L}, title = {Mesothelioma and Colorectal Cancer: Report of Four Cases with Synchronous and Metachronous Presentation.}, journal = {International journal of molecular sciences}, volume = {23}, number = {5}, pages = {}, pmid = {35269773}, issn = {1422-0067}, mesh = {*Asbestos/toxicity ; *Colorectal Neoplasms/chemically induced/diagnosis/genetics ; Humans ; *Lung Neoplasms/etiology/genetics ; *Mesothelioma/chemically induced/diagnosis ; *Mesothelioma, Malignant ; Tumor Suppressor Proteins/genetics ; Ubiquitin Thiolesterase/genetics ; }, abstract = {There is evidence that asbestos could play a role in the carcinogenesis of digestive cancers. The presence of asbestos fibres in histological samples from gastric, biliary, colon cancers has been reported, but the mechanism is still controversial. It has been hypothesised that asbestos reaches these sites, especially through contaminated water; however, some experimental studies have shown that the inhaled fibres are mobile, so they can migrate to many organs, directly or via blood and lymph flow. We report four unusual cases of colorectal cancers in patients with a long history of asbestos exposure who also developed synchronous or metachronous mesothelioma. We evaluated the roles of BRCA associated protein-1 (BAP1) and cyclin-dependent kinase inhibitor 2A (CDKN2A) in colon cancer and mesothelioma to support the hypothesis that BAP-1 and CDKN2A are tumour suppressor genes involved in disease progression, recurrence, or death in both digestive cancers and mesothelioma. Potentially, these markers may be used as predictors of worse prognosis, but we also stress the importance of clinical surveillance of exposed patients because asbestos could induce cancer in any organ.}, } @article {pmid35264891, year = {2022}, author = {Davis, A and Ke, H and Kao, S and Pavlakis, N}, title = {An Update on Emerging Therapeutic Options for Malignant Pleural Mesothelioma.}, journal = {Lung Cancer (Auckland, N.Z.)}, volume = {13}, number = {}, pages = {1-12}, pmid = {35264891}, issn = {1179-2728}, abstract = {The treatment paradigm for malignant pleural mesothelioma (MPM) has changed little in the last 18 years. Radical intent treatment, consisting of surgical resection, radiotherapy and chemotherapy, has been offered to a highly select few; however, there is little randomised evidence to validate this approach. Prior to 2020 chemotherapy with platinum and an anti-folate was the only intervention with randomised evidence to demonstrate improved overall survival (OS) in MPM. No systemic therapy had been demonstrated to improve OS in the second line setting until 2020. The publication of the Checkmate 743 trial in 2021 demonstrated a survival benefit of combination immunotherapy over standard chemotherapy in newly diagnosed patients with MPM. This finding was shortly followed by the CONFIRM trial which demonstrates a modest but significant survival benefit of second line nivolumab versus placebo in patients having previously received standard chemotherapy. The results of these trials, recent biomarker directed therapy and chemotherapy adjuncts are discussed within this review. The integration of immunotherapy for the few patients in whom radical surgical therapy is intended is currently the subject of clinical trials and offers the prospect of improving outcomes in this rare but devastating disease.}, } @article {pmid35251640, year = {2022}, author = {Rijavec, E and Biello, F and Barletta, G and Dellepiane, C and Genova, C}, title = {Novel approaches for the treatment of unresectable malignant pleural mesothelioma: A focus on immunotherapy and target therapy (Review).}, journal = {Molecular and clinical oncology}, volume = {16}, number = {4}, pages = {89}, pmid = {35251640}, issn = {2049-9469}, abstract = {Malignant pleural mesothelioma (MPM) is considered a relatively uncommon disease but its incidence is increasing worldwide. Patients affected by MPM have a very severe prognosis and have been often occupationally and environmentally exposed to asbestos. In recent years, checkpoint inhibitors have dramatically revolutionized the paradigm for the treatment of several malignancies. Several efforts have also been made to improve the survival outcomes of patients with MPM and after decades, the standard-of-care systemic treatment for unresectable MPM, based on first-line combination chemotherapy with cisplatin and pemetrexed, has changed. In addition to checkpoint inhibitors, other types of treatments, such as molecularly targeted therapy have been evaluated. However, to date, the results of these investigations are not very encouraging. The aim of the present review is to provide a comprehensive overview of the most relevant data of clinical trials regarding recent treatment strategies of MPM with a particular focus on immunotherapeutic and targeted approaches.}, } @article {pmid35236019, year = {2022}, author = {Freemantle, GG and Chetty, D and Olifant, M and Masikhwa, S}, title = {Assessment of asbestos contamination in soils at rehabilitated and abandoned mine sites, Limpopo Province, South Africa.}, journal = {Journal of hazardous materials}, volume = {429}, number = {}, pages = {127588}, doi = {10.1016/j.jhazmat.2021.127588}, pmid = {35236019}, issn = {1873-3336}, mesh = {*Asbestos ; Asbestos, Amosite ; Asbestos, Crocidolite ; Asbestos, Serpentine ; Humans ; *Mesothelioma ; Soil ; South Africa ; }, abstract = {Prior to its termination, asbestos mining in South Africa was centred on the large crocidolite fields of the present day Northern Cape, the amosite (grunerite)-crocidolite fields of Limpopo, and chrysotile fields of Mpumalanga provinces. The legacy of these activities continues to affect surrounding communities in contemporary South Africa. The asbestos fields of Limpopo host two important former mining areas at Penge and at the Bewaarkloof near Chuenespoort. A large abandoned site is located southeast of Penge at Weltevreden, where there is no evidence of any rehabilitation. Two former mines, Lagerdraai and Uitkyk, are rehabilitated sites in an extensive string of closed mines that operated in the southern Bewaarkloof. Samples from the abandoned and rehabilitated mine sites were studied using semi-quantitative X-ray powder diffraction (XRD) to determine asbestos contamination levels in soils, and to assess distribution patterns of asbestos mineral species in the surrounding soils. Only where below detection (typically 1-3 mass%) from XRD, samples were assessed optically. The Weltevreden site, with no observable rehabilitation efforts, contrasts with the rehabilitated sites at Lagerdraai and Uitkyk. The predominant asbestiform mineral species at each site were successfully identified, with underlying geological asbestos mineral distribution trends recognised in the soils at the Bewaarkloof. Trace amounts of asbestiform minerals were identified in soils downstream of the Weltevreden mine, as well as in surrounding hillsides. The results indicate that XRD is a potentially useful tool for benchmarking sites yet to be rehabilitated as well as monitoring the effectiveness of previous rehabilitation efforts. The method is also a suitable first-pass for target areas that may require more detailed, time-consuming, and costly analysis.}, } @article {pmid35223506, year = {2022}, author = {Fortarezza, F and Pezzuto, F and Marzullo, A and Cavone, D and Romano, DE and d'Amati, A and Serio, G and Vimercati, L}, title = {Molecular Pathways in Peritoneal Mesothelioma: A Minireview of New Insights.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {823839}, pmid = {35223506}, issn = {2234-943X}, abstract = {Mesothelioma is a rare malignant neoplasm with poor survival. It mainly affects the pleura (90%) but can arise in all serous cavities: peritoneum (5-10%), pericardium and tunica vaginalis testis (<1%). The onset of pleural mesothelioma is strictly related to asbestos exposure with a long latency time. The causal link with asbestos has also been suggested for peritoneal mesothelioma, while the importance of exposure in the onset of pericardial and tunica vaginalis testis mesotheliomas is not well known. Mesothelioma remains an aggressive and fatal disease with a five-year mortality rate higher than 95%. However, new therapeutic approaches based on molecular-targeted and immunomodulatory therapies are being explored but have conflicting results. In this context, the identification of critical targets appears mandatory. Awareness of the molecular and physiological changes leading to the neoplastic degeneration of mesothelial cells and the identification of gene mutations, epigenetic alterations, gene expression profiles and altered pathways could be helpful for selecting targetable mechanisms and molecules. In this review, we aimed to report recent research in the last 20 years focusing on the molecular pathways and prognostic factors in peritoneal mesothelioma and their possible diagnostic and therapeutic implications.}, } @article {pmid35216091, year = {2022}, author = {Štrbac, D and Dolžan, V}, title = {Novel and Future Treatment Options in Mesothelioma: A Systematic Review.}, journal = {International journal of molecular sciences}, volume = {23}, number = {4}, pages = {}, pmid = {35216091}, issn = {1422-0067}, support = {P1-170, L3-8203, and L3-2622.//Slovenian Research Agency/ ; }, mesh = {Animals ; Cell- and Tissue-Based Therapy/methods ; Clinical Trials as Topic ; Humans ; Immunotherapy/methods ; Mesothelioma/*drug therapy/immunology/*therapy ; Receptors, Chimeric Antigen/immunology ; T-Lymphocytes/immunology ; Tumor Microenvironment/drug effects ; }, abstract = {Mesothelioma is a rare tumor, frequently associated with asbestos exposure, arising from pleura and peritoneum. Traditionally, diagnosis and treatment have been difficult in a clinical setting. The treatment is based on a trimodal approach involving surgery, chemotherapy, and radiotherapy. The introduction of chemotherapy improved the overall survival. However, the regimen of pemetrexed/cisplatin doublet has not been changed as a standard treatment since 2004. Novel combinations of ipilimumab and nivolumab have only been approved for clinical use in late 2020. The aim of this review was to systematically summarize findings on novel treatment options in mesothelioma. We searched available medical databases online, such as PubMed and Clinicaltrials.gov, to systematically review the literature on novel approaches in immunotherapy, vaccines, and Chimeric Antigen Receptor (CAR)-T cell therapy in mesothelioma. We manually screened 1127 articles on PubMed and 450 trials on ClinicalTrials.gov, and 24 papers and 12 clinical trials published in the last ten years were included in this review. Immunotherapy that was swiftly introduced to treat other thoracic malignancies was slow to reach desirable survival endpoints in mesothelioma, possibly due to limited patient numbers. Novel treatment approaches, such as CAR-T cell therapy, are being investigated. As the incidence of mesothelioma is still rising globally, novel treatment options based on a better understanding of the tumor microenvironment and the genetic drivers that modulate it are needed to support future precision-based therapies.}, } @article {pmid35211727, year = {2022}, author = {Spinazzè, A and Consonni, D and Borghi, F and Mazzucchelli, LA and Rovelli, S and Cattaneo, A and Zellino, C and Dallari, B and Pesatori, AC and Kromhout, H and Peters, S and Riboldi, L and Mensi, C and Cavallo, DM}, title = {Development of a Crosswalk to Translate Italian Occupation Codes to ISCO-68 Codes.}, journal = {Annals of work exposures and health}, volume = {66}, number = {6}, pages = {815-821}, doi = {10.1093/annweh/wxac009}, pmid = {35211727}, issn = {2398-7316}, mesh = {*Asbestos ; Female ; Humans ; Male ; *Mesothelioma/epidemiology ; *Occupational Exposure ; Occupations ; }, abstract = {In occupational epidemiology, job coding is an important-but time-consuming-step in assigning exposure. We implemented a tool (i.e. a crosswalk) to translate occupation codes from the Italian (ISTAT-CIP-91, n = 6319 five-digit job codes) to the International Standard Classification of Occupations (ISCO-68, n = 1881 five-digit job codes). The former is currently used in Italy for various purposes (e.g. in the National Mesothelioma Registry). The latter has been used in several studies on occupational cancers because it facilitates communication of results to the scientific community and, most importantly, because some job exposure matrices (JEMs) are based on international codes. Three authors created a table containing the crosswalk structure, providing an interpretation for each of the ISTAT-CIP-91 codes job descriptions and then manually recoding them according to ISCO-68. Two other authors independently revised it. The performance of the final version was assessed by comparison with results obtained by manual ISCO-68 coding performed in two previous case-control studies on asbestos and mesothelioma. More specifically, the automatically obtained ISCO-68 codes were merged with a JEM (DOM-JEM). The resulting individual asbestos exposure estimates (ever versus never exposed) were compared to those originally obtained (using the same DOM-JEM) from manual translation of ISTAT-CIP-91 to ISCO-68 (considered as the 'gold standard'). In the first study, among 159 peritoneal mesothelioma cases (400 job codes), Cohen's kappa was 0.91, sensitivity 0.95, and specificity 0.96. In the second study, among 716 pleural mesothelioma cases and controls (4400 job codes) kappa was 0.86, sensitivity 0.94, and specificity 0.91. Performance was better among in women. For men, performance was lower among cases than among controls (kappa 0.70, sensitivity 0.95, specificity 0.72 versus kappa 0.87, sensitivity 0.97, and specificity 0.92). In conclusion, the proposed tool allowed a rapid translation of thousands of job codes with good to excellent accuracy. The table containing ISTAT-CIP-91 codes and job descriptions and the corresponding ISCO-68 codes and job descriptions is made publicly available and can be freely used for epidemiological analyses in Italy and international collaborations.}, } @article {pmid35207583, year = {2022}, author = {Caraballo-Arias, Y and Caffaro, P and Boffetta, P and Violante, FS}, title = {Quantitative Assessment of Asbestos Fibers in Normal and Pathological Pleural Tissue-A Scoping Review.}, journal = {Life (Basel, Switzerland)}, volume = {12}, number = {2}, pages = {}, pmid = {35207583}, issn = {2075-1729}, abstract = {BACKGROUND: pleural mesothelioma is a rare cancer in the general population, but it is more common in subjects occupationally exposed to asbestos. Studies with asbestos fiber quantification in pleural tissue are scarce: for this reason, we aimed at undertaking a scoping review to summarize the evidence provided by studies in which asbestos fibers were determined by electron microscopy (SEM or TEM) in human pleural tissues, whether normal or pathologic.

MATERIALS AND METHODS: A scoping review of articles that quantified asbestos fibers in human pleural tissue (normal or pathologic) by electron microscopy (SEM or TEM), in subjects with asbestos exposure (if any) was performed.

RESULTS: The 12 studies selected comprised 137 cases, out of which 142 samples were analyzed. Asbestos fibers were detected in 111 samples (78%) and were below the detectable limit in 31 samples (22%). The concentration of asbestos fibers detected in the positive samples was distributed from as low as 0.01 mfgdt (millions of fibers per gram of dry tissue) up to 240 mfgdt. However, the minimum concentration of fibers overlaps in the three types of tissues (normal pleura, pleural plaque, mesothelioma) in terms of magnitude; therefore, it is not possible to distinguish a definite pattern which differentiates one tissue from the other.

CONCLUSIONS: The studies included were heterogeneous as to the representativeness of the samples and analytical techniques; the possibility of false negatives must be considered. It would be desirable to systematically search for asbestos fibers to fill the knowledge gap about the presence of asbestos fibers in normal or pathological pleural tissue in order to better understand the development of the different pleural diseases induced by this mineral.}, } @article {pmid35206274, year = {2022}, author = {Dalsgaard, SB and Würtz, ET and Hansen, J and Røe, OD and Omland, Ø}, title = {A Cohort Study on Cancer Incidence among Women Exposed to Environmental Asbestos in Childhood with a Focus on Female Cancers, including Breast Cancer.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {4}, pages = {}, pmid = {35206274}, issn = {1660-4601}, mesh = {*Asbestos/toxicity ; *Breast Neoplasms/complications ; Child ; Cohort Studies ; Environmental Exposure/adverse effects ; Female ; Humans ; Incidence ; Italy/epidemiology ; *Lung Neoplasms/chemically induced/etiology ; *Mesothelioma/epidemiology ; *Occupational Exposure/adverse effects ; }, abstract = {OBJECTIVES: To examine the risk of cancer in former school children exposed to environmental asbestos in childhood with a focus on female cancers, including breast cancer.

METHODS: We retrieved a cohort of females (n = 6024) attending four schools located in the neighborhood of a large asbestos cement plant in Denmark. A reference cohort was frequency-matched 1:9 (n = 54,200) in sex and five-year age intervals. Using Danish registries, we linked information on historical employments, relatives' employments, cancer, and vital status. We calculated standardized incidence rates (SIRs) for all and specific cancers, comparing these rates with the reference cohort. Hazard ratios were calculated for selected cancers adjusted for occupational and familial asbestos exposure.

RESULTS: For cancer of the corpus uteri (SIR 1.29, 95% CI 1.01-1.66) and malignant mesothelioma (SIR 7.26, 95% CI 3.26-16.15), we observed significantly increased incidences. Occupationally, asbestos exposure had a significantly increased hazard ratio for cancer in the cervix, however, a significantly lower risk of ovarian cancer. The overall cancer incidence was similar to that of the reference cohort (SIR 1.02, 95% CI 0.96-1.07). The risk of cancer of the lung was increased for those exposed to occupational asbestos, those with family members occupationally exposed to asbestos and for tobacco smokers.

CONCLUSIONS: In our study, environmental asbestos exposure in childhood is associated with an increased risk of cancer of the corpus uteri and malignant mesothelioma in women.}, } @article {pmid35205798, year = {2022}, author = {Shah, R and Klotz, LV and Glade, J}, title = {Current Management and Future Perspective in Pleural Mesothelioma.}, journal = {Cancers}, volume = {14}, number = {4}, pages = {}, pmid = {35205798}, issn = {2072-6694}, abstract = {Pleural mesothelioma is an aggressive malignancy arising from pleural mesothelial cell lining, predominantly associated with prior exposure to asbestos. The ban on asbestos use has led to its lower incidence in many countries, but globally the disease burden is expected to rise. Therefore, well-planned research is needed to develop more effective, tolerable and affordable drugs. The development of novel treatment has been too slow, with only two regimens of systemic therapy with robust phase 3 data approved formally to date. The treatment scenario for resectable disease remains controversial. However, recent developments in the understanding of disease and clinical trials have been encouraging, and may add better treatment options in the coming years. In this review, we discuss the current treatment options for pleural mesothelioma and shed light on some recent studies and ongoing trials.}, } @article {pmid35204402, year = {2022}, author = {Foddis, R and Franzini, M and Bonotti, A and Marino, R and Silvestri, R and Fallahi, P and Chiappino, D and Emdin, M and Paolicchi, A and Cristaudo, A}, title = {Big and Free Fractions of Gamma-Glutamyltransferase: New Diagnostic Biomarkers for Malignant Mesothelioma?.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {12}, number = {2}, pages = {}, pmid = {35204402}, issn = {2075-4418}, support = {PRA 2017//University of Pisa/ ; }, abstract = {Malignant pleural mesothelioma (MPM) is a cancer mainly caused by asbestos fiber inhalation, characterized by an extremely long latency and poor prognosis. Recently, researchers have focused on testing the diagnostic ability of several biomarkers. Gamma-Glutamyltransferase (GGT) has been demonstrated to be the sum of several GGT sub-fractions activity, classified based on their molecular weight in big-GGT, medium-GGT, small-GGT, and free-GGT. This work aims to evaluate whether specific GGT fractional enzymatic activity patterns could be helpful in MPM diagnosis. We analyzed blood samples from 175 workers previously exposed to asbestos, 157 non-exposed healthy subjects, and 37 MPM patients through a molecular exclusion chromatographic method. We found a specific profile of GGT fractions activity, significantly associated with MPM, resulting in an increase in b-, m- activity, along with an evident, yet not significant, decrease in f-activity. Receiver-operating characteristic (ROC) analysis showed that the best Area Under Curve (AUC) value resulted from the combined index b/f (0.679, 95% CI: 0.582-0.777). Combining the b-/f-GGT activity with the levels of serum mesothelin-related protein (SMRP; another promising MPM biomarker) improved the diagnostic accuracy, increasing the AUC value to 0.875 (95% CI: 0.807-0.943, p = <0.0001). Since MPM has a specific pattern of GGT enzymatic activity, we could hypothesize that GGT fractions play different specific biochemical roles. The improvement in the diagnostic power given by the combination of these two biomarkers confirms that the strategy of biomarkers combination might be a better approach for MPM diagnosis.}, } @article {pmid35201802, year = {2022}, author = {Lond, B and Quincey, K and Apps, L and Darlison, L and Williamson, I}, title = {The experience of living with mesothelioma: A meta-ethnographic review and synthesis of the qualitative literature.}, journal = {Health psychology : official journal of the Division of Health Psychology, American Psychological Association}, volume = {41}, number = {5}, pages = {343-355}, doi = {10.1037/hea0001166}, pmid = {35201802}, issn = {1930-7810}, mesh = {*Adaptation, Psychological ; Europe ; Humans ; *Mesothelioma/ethnology/psychology/therapy ; }, abstract = {OBJECTIVE: Mesothelioma is a life limiting cancer caused by previous exposure to asbestos. Due to the continued use of asbestos products internationally, the condition presents an increasing risk to global health with case numbers peaking in industrially developed nations. With the cancer reducing patient well-being, this study aimed to synthesizes the qualitative findings of studies exploring the experiences of patients living with mesothelioma to generate new conceptual insights and guide therapeutic care.

METHOD: Thirteen databases were systematically searched: Academic Search Premier, BioMed Central, British Nursing Database, CINAHL Plus, Cochrane Library, Europe PubMed Central, MEDLINE, PsycARTICLES, PsycINFO, Science Direct, Scopus, Social Care Online, and Web of Science, between August and September 2020. Included articles were subject to quality appraisal using CASP checklists, and their respective findings analyzed using a metaethnographic form of qualitative data synthesis.

RESULTS: Twenty-two articles met the inclusion criteria, and the data synthesis produced three themes: (1) "complex trauma"; (2) "psycho-behavioral coping strategies"; and (3) "external sources of support." Combined, these themes form a novel conceptual framework and awareness of the patient experience that presents the lived trauma of disease alongside a patients coping processes and support pathways.

CONCLUSION: Robust therapeutic support is needed to address the psychosocial and existential burden shouldered by people with mesothelioma. Therapies that promote sentiments of acceptance, hope, and benefit finding are proposed alongside initiatives that foster patient empowerment and meaning, and further promote patient choice in deciding end-of-life care. Recommendations for future research are also made. (PsycInfo Database Record (c) 2022 APA, all rights reserved).}, } @article {pmid35149582, year = {2022}, author = {van Kooten, JP and Belderbos, RA and von der Thüsen, JH and Aarts, MJ and Verhoef, C and Burgers, JA and Baas, P and Aalbers, AGJ and Maat, APWM and Aerts, JGJV and Cornelissen, R and Madsen, EVE}, title = {Incidence, treatment and survival of malignant pleural and peritoneal mesothelioma: a population-based study.}, journal = {Thorax}, volume = {77}, number = {12}, pages = {1260-1267}, pmid = {35149582}, issn = {1468-3296}, mesh = {Humans ; Male ; Female ; Aged, 80 and over ; *Mesothelioma, Malignant ; Incidence ; *Pleural Neoplasms/epidemiology/therapy ; Pleura/pathology ; *Lung Neoplasms/epidemiology/therapy ; *Mesothelioma/epidemiology/therapy/diagnosis ; *Asbestos ; *Peritoneal Neoplasms/epidemiology/therapy/etiology ; }, abstract = {INTRODUCTION: Malignant mesothelioma (MM) is an aggressive cancer that primarily arises from the pleura (MPM) or peritoneum (MPeM), mostly due to asbestos exposure. This study reviewed the Dutch population-based incidence, treatment and survival since the national ban on asbestos in 1993.

MATERIALS AND METHODS: Patients with MPM or MPeM diagnosed from 1993 to 2018 were selected from the Dutch cancer registry. Annual percentage change (APC) was calculated for (age-specific and sex-specific) revised European standardised incidence rates (RESR). Treatment pattern and Kaplan-Meier overall survival analyses were performed.

RESULTS: In total, 12 168 patients were included in the study. For male patients younger than 80 years, the MM incidence significantly decreased in the last decade (APC ranging between -9.4% and -1.8%, p<0.01). Among both male and female patients aged over 80 years, the incidence significantly increased during the entire study period (APC 3.3% and 4.6%, respectively, p<0.01). From 2003 onwards, the use of systemic chemotherapy increased especially for MPM (from 9.3% to 39.4%). Overall, 62.2% of patients received no antitumour treatment. The most common reasons for not undergoing antitumour treatment were patient preference (42%) and performance status (25.6%). The median overall survival improved from 7.3 (1993-2003) to 8.9 (2004-2011) and 9.3 months from 2012 to 2018 (p<0.001).

CONCLUSION: The peak of MM incidence was reached around 2010 in the Netherlands, and currently the incidence is declining in most age groups. The use of systemic chemotherapy increased from 2003, which likely resulted in improved overall survival over time. The majority of patients do not receive treatment though and prognosis is still poor.}, } @article {pmid35143119, year = {2022}, author = {Louw, A and van Vliet, C and Peverall, J and Colkers, S and Acott, N and Creaney, J and Lee, YCG and Chai, SM}, title = {Analysis of early pleural fluid samples in patients with mesothelioma: A case series exploration of morphology, BAP1, and CDKN2A status with implications for the concept of mesothelioma in situ in cytology.}, journal = {Cancer cytopathology}, volume = {130}, number = {5}, pages = {352-362}, doi = {10.1002/cncy.22548}, pmid = {35143119}, issn = {1934-6638}, mesh = {Biomarkers, Tumor/metabolism ; Cyclin-Dependent Kinase Inhibitor p16/genetics ; Homozygote ; Humans ; In Situ Hybridization, Fluorescence ; *Lung Neoplasms/diagnosis/genetics ; *Mesothelioma/diagnosis/genetics ; *Mesothelioma, Malignant ; *Pleural Neoplasms/diagnosis/genetics ; Retrospective Studies ; Sequence Deletion ; Tumor Suppressor Proteins/genetics ; Ubiquitin Thiolesterase/genetics ; }, abstract = {BACKGROUND: The concept of mesothelioma in situ has been revisited and is a new World Health Organization diagnostic entity. The definition centers on ancillary techniques used in pleural mesothelioma (PM) assessment. At the authors' institution, most PM diagnoses are made on cytologic specimens. Effusion samples obtained before definitive PM diagnosis were interrogated using BRCA1-associated protein 1 gene (BAP1), cyclin-dependent kinase inhibitor 2A gene (CDKN2A) and cytologic evaluation to assess whether early or possible in situ disease could be characterized.

METHODS: All cases of PM diagnosed between January 2008 and December 2019 were identified at a tertiary referral center. Patients who had a pleural fluid sample collected 24 months before the diagnosis were selected, numbering 8 in total. The cytomorphology of each sample was reviewed; and, retrospectively, BAP1 immunohistochemistry (IHC) and CDKN2A fluorescence in situ hybridization (FISH) were performed on initial and diagnostic samples.

RESULTS: The initial samples were deemed benign in 5 cases and atypical mesothelial proliferations in 3 cases. A spectrum of apparently normal to atypical cytomorphologic changes was identified. BAP1 loss was present in 6 of 8 initial cases, whereas CDKN2A homozygous deletion was identified in 1 of 7 initial cases. Either abnormality was identified in 7 of 8 initial samples.

CONCLUSIONS: Detectable abnormalities of BAP1 IHC and CDKN2A FISH were present in pleural fluid specimens before the development of cytomorphologic features diagnostic of PM. This is the largest series to date describing cytology samples early in the course of PM development, thereby highlighting a possible cytological equivalent for mesothelioma in situ.}, } @article {pmid35127504, year = {2021}, author = {Endo, I and Amatya, VJ and Kushitani, K and Kambara, T and Nakagiri, T and Fujii, Y and Takeshima, Y}, title = {Insulin-Like Growth Factor 2 mRNA Binding Protein 3 Promotes Cell Proliferation of Malignant Mesothelioma Cells by Downregulating p27[Kip1].}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {795467}, pmid = {35127504}, issn = {2234-943X}, abstract = {Malignant mesothelioma is a tumor with a poor prognosis, mainly caused by asbestos exposure and with no adequate treatment yet. To develop future therapeutic targets, we analyzed the microarray dataset GSE 29370 of malignant mesothelioma and reactive mesothelial hyperplasia, downloaded from the Gene Expression Omnibus (GEO) database. We identified insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) as one of the significantly upregulated genes in malignant mesothelioma. IGF2BP3 functions as an oncoprotein in many human cancers; however, to our knowledge, this is the first study on the biological function of IGF2BP3 in malignant mesothelioma cells. The knockdown of IGF2BP3 in malignant mesothelioma cells resulted in the suppression of cell proliferation with an increase in the proportion of cells in the G1 phase of the cell cycle. Furthermore, knockdown of IGF2BP3 inhibited cell migration and invasion. We focused on the cell cycle assay to investigate the role of IGF2BP3 in cell proliferation in malignant mesothelioma. Among the various proteins involved in cell cycle regulation, the expression of p27 Kip1 (p27) increased significantly upon IGF2BP3 knockdown. Next, p27 siRNA was added to suppress the increased expression of p27. The results showed that p27 knockdown attenuated the effects of IGF2BP3 knockdown on cell proliferation and G1 phase arrest. In conclusion, we found that IGF2BP3 promotes cell proliferation, a critical step in tumorigenesis, by suppressing the expression of p27 in malignant mesothelioma.}, } @article {pmid35114507, year = {2022}, author = {Repo, P and Staskiewicz, A and Sutinen, E and Rönty, M and Tero T Kivelä, and Myllärniemi, M and Turunen, JA}, title = {BAP1 germline variants in Finnish patients with malignant mesothelioma.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {165}, number = {}, pages = {102-107}, doi = {10.1016/j.lungcan.2022.01.017}, pmid = {35114507}, issn = {1872-8332}, abstract = {OBJECTIVES: Although asbestos exposure is the most common cause of malignant mesothelioma (MM), an aggressive cancer of the pleura or peritoneum, up to 7% of patients harbor a genetic predisposition to MM. Pathogenic germline variants in the BRCA1-associated protein 1 (BAP1) gene cause a dominantly inherited tumor predisposition syndrome, BAP1-TPDS, in which MM is the second most common associated cancer. Other frequent cancers in BAP1-TPDS are uveal melanoma (UM), cutaneous melanoma and renal cell carcinoma. Additionally patients can exhibit benign skin lesions, BAP1-inactivated nevi (BIN). Most BINs arise sporadically, but patients with BAP1-TPDS may harbor multiple BINs before other tumors or as the only indication of the syndrome. Our objective was to establish the frequency of pathogenic germline BAP1 variants in Finnish patients with MM.

MATERIALS AND METHODS: 56 DNA samples archived in the Helsinki Biobank from Finnish patients with MM were sequenced for germline BAP1 variations. Formalin fixed paraffin embedded nevi from a pathogenic variant carrier were subjected to immunohistochemistry and exome sequencing.

RESULTS: Sanger sequencing identified one patient with Finnish founder mutation c.1780_1781insT, p.(G549Vfs*49) in BAP1. The carrier was diagnosed with MM over fifteen years before the cohorts mean onset age (mean 68, range 27 to 82) although the patient had no asbestos exposure or family history of BAP1-TPDS. However, the patient had three BINs removed prior to the MM. The c.1780_1781insT is now found from five Finnish BAP1-TPDS families with unknown common ancestor.

CONCLUSION: The frequency of pathogenic germline BAP1 variants in Finnish patients with MM is 1.8 % (95 % CI, 0.04 to 9.2), comparable to the frequency in Finnish patients with UM (1.9 %). The frequency of recurring BINs in patients with BAP1-TPDS should be studied further and genetic testing for BAP1 variants considered if the patient has ≥ 2 BAP1-TPDS core tumors, including BINs.}, } @article {pmid35102573, year = {2022}, author = {LeMasters, G and Lockey, JE and Hilbert, TJ and Burkle, JW and Rice, CH}, title = {Mortality of workers employed in refractory ceramic fiber manufacturing: An update.}, journal = {Journal of applied toxicology : JAT}, volume = {42}, number = {7}, pages = {1287-1293}, doi = {10.1002/jat.4295}, pmid = {35102573}, issn = {1099-1263}, support = {//High Temperature Insulation Wool Coalition to the University of Cincinnati, College of Medicine/ ; }, mesh = {Ceramics ; Cohort Studies ; Humans ; *Lung Neoplasms/mortality ; *Mesothelioma/mortality ; *Neoplasms/mortality ; *Occupational Diseases/complications/mortality ; *Occupational Exposure/adverse effects ; }, abstract = {This study evaluates the possible association between refractory ceramic fiber (RCF) exposure and all causes of death. Current and former employees (n = 1,119) hired from 1952 to 1999 at manufacturing facilities in New York (NY) state and Indiana were included. Work histories and quarterly plant-wide sampling from 1987 to 2015 provided cumulative fiber exposure (CFE) estimates. The full cohort was evaluated as well as individuals with lower and higher exposure, <45 and ≥45 fiber-months/cc. The Life-Table-Analysis-System was used for all standardized mortality rates (SMRs). Person-years at risk were accumulated from start of employment until 12/31/2019 or date of death. There was no significant association with all causes, all cancers, or lung cancer in any group. In the higher exposed, there was a significant elevation in both malignancies of the "urinary organs" (SMR = 3.59, 95% confidence interval [CI] 1.44, 7.40) and "bladder or other urinary site" (SMR = 4.04, 95% CI 1.10, 10.36), which persisted in comparison to regional mortality rates from NY state and Niagara County. However, six of the nine workers with urinary cancers were known smokers. In the lower exposed, there was a significant elevation in malignancies of the lymphatic and hematopoietic system (SMR = 2.54, 95% CI 1.27, 4.55) and leukemia (SMR = 4.21, 95% CI 1.69, 8.67). There was one pathologically unconfirmed mesothelioma death. A second employee currently living with a pathologically confirmed mesothelioma was identified, but the SMR was non-significant when both were included in the analyses. The association of these two mesothelioma cases with RCF exposure alone is unclear because of potential past exposure to asbestos.}, } @article {pmid35100476, year = {2022}, author = {Hyland, RA and Chrzanowska, A and Hannaford-Turner, K and Davis, A and Ke, H and Bradbury, L and Nagrial, A and McCaughan, B and Hui, R and van Zandwijk, N and Takahashi, K and Kao, SC}, title = {Asbestos-related lung cancer: Clinical characteristics and survival outcomes in an Australian cohort seeking workers compensation.}, journal = {Asia-Pacific journal of clinical oncology}, volume = {18}, number = {5}, pages = {e448-e455}, doi = {10.1111/ajco.13664}, pmid = {35100476}, issn = {1743-7563}, mesh = {*Asbestos/analysis/toxicity ; Australia ; Humans ; *Lung Neoplasms/epidemiology/etiology ; *Mesothelioma ; *Occupational Exposure/adverse effects ; Workers' Compensation ; }, abstract = {BACKGROUND AND OBJECTIVES: Due to difficulties in identifying sufficient-sized cohorts there remains uncertainty about prognostic and clinical differences that may be unique to asbestos-related lung cancer (ARLC). In this study, we use the Helsinki Criteria to define a group of ex-workers with lung cancer attributable to asbestos exposure and investigate differences that may exist.

METHODS: A total of 529 patients seeking workers' compensation for their lung cancer were assigned to either ARLC or the non-ARLC based on parameters defined in the Helsinki Criteria. Clinical and survival details were collected and analyzed.

RESULTS: In our study population, ARLC patients were on average older (72.1 ± 7.8) than non-ARLC patients (66.5 ± 10.2, P < 0.001) and were more likely to be diagnosed as a result of incidental findings or screening program (P < 0.001). The groups were similar in terms of clinical characteristics with the only difference being that plaques were more prevalent among ARLC patients (P < 0.001). Differences were observed for median overall survival (OS), ARLC (9 months) and non-ARLC (13 months, P = 0.005), as well for treatment (P = 0.01). After adjusting for age, however, these differences disappeared.

CONCLUSIONS: Age at diagnosis, pleural plaques, and asymptomatic presentation were the attributes that we identified as significantly different between asbestos-related cancer and other lung cancers. In this cohort, ARLC patients were older diagnosis and with worse overall survival.}, } @article {pmid35098897, year = {2023}, author = {Le, HT and Dinh, HT and Ngo, TT}, title = {Asbestos dust concentrations and health conditions of workers at asbestos-cement corrugated sheet production manufacturers in Vietnam: a nationwide assessment.}, journal = {International journal of occupational safety and ergonomics : JOSE}, volume = {29}, number = {1}, pages = {263-267}, doi = {10.1080/10803548.2022.2035510}, pmid = {35098897}, issn = {2376-9130}, mesh = {Humans ; *Occupational Exposure/analysis ; Vietnam ; *Asbestos ; *Mesothelioma ; Dust/analysis ; }, abstract = {This study examined contemporary concentrations of asbestos dust during production and the health conditions of workers at asbestos-cement corrugated sheet production manufacturers in Vietnam. A nationwide survey was conducted on 28 factories (with 206 air samples) and 2459 workers. Asbestos fiber dust and the health status of workers were assessed. Results showed that 108/206 (52.4%) samples had asbestos fiber dust. The average concentration of asbestos fibers was 0.19 ± 0.14 fibers/ml. The percentage of workers with thickened pleural lesions/pleural calcification nodules was low. More studies are needed to evaluate the effectiveness of biomarkers in preventing the onset of lung cancer and mesothelioma in workers.}, } @article {pmid35098108, year = {2021}, author = {Zolondick, AA and Gaudino, G and Xue, J and Pass, HI and Carbone, M and Yang, H}, title = {Asbestos-induced chronic inflammation in malignant pleural mesothelioma and related therapeutic approaches-a narrative review.}, journal = {Precision cancer medicine}, volume = {4}, number = {}, pages = {}, pmid = {35098108}, issn = {2617-2216}, support = {R01 CA160715/CA/NCI NIH HHS/United States ; R01 CA237235/CA/NCI NIH HHS/United States ; R01 ES030948/ES/NIEHS NIH HHS/United States ; U01 CA214195/CA/NCI NIH HHS/United States ; }, abstract = {OBJECTIVE: The aim of this review is addressing the mechanisms of asbestos carcinogenesis, including chronic inflammation and autophagy-mediated cell survival, and propose potential innovative therapeutic targets to prevent mesothelioma development or improve drug efficacy by reducing inflammation and autophagy.

BACKGROUND: Diffuse malignant pleural mesothelioma is an aggressive cancer predominantly related to chronic inflammation caused by asbestos exposure. Millions of individuals have been exposed to asbestos or to other carcinogenic mineral fibers occupationally or environmentally, resulting in an increased risk of developing mesothelioma. Overall patient survival rates are notably low (about 8-14 months from the time of diagnosis) and mesothelioma is resistant to existing therapies. Additionally, individuals carrying inactivating germline mutations in the BRCA-associated protein 1 (BAP1) gene and other genes are predisposed to developing cancers, prevalently mesothelioma. Their risk of developing mesothelioma further increases upon exposure to asbestos. Recent studies have revealed the mechanisms and the role of inflammation in asbestos carcinogenesis. Biomarkers for asbestos exposure and malignant mesothelioma have also been identified. These findings are leading to the development of novel therapeutic approaches to prevent or delay the growth of mesothelioma.

METHODS: Review of full length manuscripts published in English from January 1980 to February 2021 gathered from PubMed.gov from the National Center of Biotechnology Information and the National Library of Medicine were used to inform this review.

CONCLUSION: Key regulators of chronic inflammation mediate asbestos-driven mesothelial cell transformation and survival through autophagic pathways. Recent studies have elucidated some of the key mechanisms involved in asbestos-induced chronic inflammation, which are largely driven by extracellular high mobility group box 1 (HMGB1). Upon asbestos exposure, mesothelial cells release HMGB1 from the nucleus to the cytoplasm and extracellular space, where HMGB1 initiates an inflammatory response. HMGB1 translocation and release also activates autophagy and other pro-survival mechanisms, which promotes mesothelioma development. HMGB1 is currently being investigated as a biomarker to detect asbestos exposure and to detect mesothelioma development in its early stage when therapy is more effective. In parallel, several approaches inhibiting HMGB1 activities have been studied and have shown promising results. Moreover, additional cytokines, such as IL-1β and TNF-α are being targeted to interfere with the inflammatory process that drives mesothelioma growth. Developing early detection methods and novel therapeutic strategies is crucial to prolong overall survival of patients with mesothelioma. Novel therapies targeting regulators of asbestos-induced inflammation to reduce mesothelioma growth may lead to clinical advancements to benefit patients with mesothelioma.}, } @article {pmid35089637, year = {2022}, author = {Yue, L and Luo, Y and Jiang, L and Sekido, Y and Toyokuni, S}, title = {PCBP2 knockdown promotes ferroptosis in malignant mesothelioma.}, journal = {Pathology international}, volume = {72}, number = {4}, pages = {242-251}, doi = {10.1111/pin.13209}, pmid = {35089637}, issn = {1440-1827}, support = {19-251//Princess Takamatsu Cancer Research Fund/ ; JPMJCR19H4//Core Research for Evolutional Science and Technology/ ; JP19H05462 and JP20H05502//Japan Society for the Promotion of Science/ ; //JST CREST/ ; //JSPS Kakenhi/ ; //Research Grant of the Princess Takamatsu Cancer Research Fund/ ; }, mesh = {Animals ; *Ferroptosis ; Ferrous Compounds/metabolism ; Gene Knockdown Techniques ; Humans ; Iron/metabolism ; *Mesothelioma, Malignant/genetics/metabolism ; *RNA-Binding Proteins/genetics/metabolism ; Rats ; }, abstract = {Malignant mesothelioma (MM) is still increasing worldwide. The pathogenesis depends on asbestos-induced iron accumulation, which eventually leads to ferroptosis-resistance of mesothelial cells via somatic mutations. Poly (rC)-binding proteins 1 and 2 (PCBP1/2) are recently recognized cytosolic Fe(II) chaperones. Here we studied the role of PCBP1/2 in rat/human mesothelial and MM cells as well as rat/human MM specimens. Normal peritoneal mesothelial cells in rats exhibited PCBP1 but not PCBP2 immunopositivity whereas primary/immortalized mesothelial cells showed PCBP1/2 immunopositivity. Rat MM specimens induced by intraperitoneal injection of chrysotile, including in situ lesion, revealed PCBP1/2 immunopositivity (90% for both) in the nucleus and cytoplasm with a tendency of higher expression in epithelioid subtype. Knockdown of PCBP2 but not PCBP1 significantly decreased both TfR1 and FTH expression in MM cells with inhibition of proliferation, indicating stagnation of intracellular iron transport. Erastin, a cysteine-deprivation type ferroptosis inducer, decreased the expression of both PCBP1/2 in MM cells. Furthermore, PCBP2 knockdown significantly increased the sensitivity of MM cells to erastin-induced ferroptosis with increased catalytic Fe(II). In conclusion, PCBP2 works for ferroptosis-resistance not only during mesothelial carcinogenesis but also in MM, which warrants further investigation as a novel therapeutic target.}, } @article {pmid35089066, year = {2022}, author = {Kelsey, K}, title = {Epigenetics, environment and epidemiology: an interview with Karl Kelsey.}, journal = {Epigenomics}, volume = {14}, number = {6}, pages = {323-326}, doi = {10.2217/epi-2022-0008}, pmid = {35089066}, issn = {1750-192X}, mesh = {*Arsenic ; Biomarkers ; Case-Control Studies ; Epigenesis, Genetic ; Epigenomics ; Female ; Humans ; Male ; *Urinary Bladder Neoplasms ; }, abstract = {In this interview, Professor Karl Kelsey speaks with Storm Johnson, Commissioning Editor for Epigenomics, on his work to date in the field of environmental epigenomics and epidemiology. Dr Karl Kelsey, MD, MOH is a Professor of Epidemiology and Pathology and Laboratory Medicine at Brown University. He is the Founding Director of the Center for Environmental Health and Technology and Head of the Environmental Health Section at the Department of Epidemiology. Dr Kelsey is interested in the application of laboratory-based biomarkers in environmental disease, with experience in chronic disease epidemiology and tumor biology. The goals of his work include a mechanistic understanding of individual susceptibility to exposure-related cancers. In addition, his laboratory is interested in tumor biology, investigating somatic alterations in tumor tissue from the patients who have developed exposure-related cancers. This work involves the use of an epidemiologic approach to characterize epigenetic and genetic alteration of genes in the causal pathway for malignancy. Active work includes several studies of individual susceptibility to cancer. Dr Kelsey's laboratory mainly investigates susceptibility to smoking-related lung cancer and studies multi-racial and ethnic populations. In addition, the laboratory is also involved with the study of inherited susceptibility to brain tumors and pancreatic cancer. Major case control studies that are ongoing in the laboratory include studies designed to understand inherited and acquired susceptibility in head and neck cancers. The laboratory is also involved in a case control study of asbestos-associated mesothelioma, arsenic exposure, cigarette smoking and bladder cancer. Considerable work is being devoted to understanding the mechanisms of action of both asbestos and arsenic including their ability to affect promoter methylation and gene silencing in carcinogenesis. Recent laboratory studies includes an interest in using newly developed DNA methylation biomarkers to probe immune profiles from archived blood. Dr Kelsey received his MD from the University of Minnesota and Masters of Occupational Health from Harvard University.}, } @article {pmid35081587, year = {2022}, author = {Tao, XG and Curriero, FC and Chee, EM and Mahesh, M}, title = {Updated Standardized Mortality Ratio Evaluation of Disease Risks of Shipyard Workers Exposed to Low Dose Ionizing Radiation.}, journal = {Journal of occupational and environmental medicine}, volume = {64}, number = {4}, pages = {e224-e230}, doi = {10.1097/JOM.0000000000002491}, pmid = {35081587}, issn = {1536-5948}, mesh = {*Asbestos ; *Asbestosis ; Humans ; *Lung Neoplasms ; Male ; *Mesothelioma ; *Occupational Diseases/etiology ; *Occupational Exposure/adverse effects ; Radiation, Ionizing ; }, abstract = {OBJECTIVE: To examine the risk of diseases among industrial workers with low and fractionated radiation exposures.

METHOD: The 372,047 US male shipyard radiation and non-radiation workers were followed for 54 years and compared with US men using standardized mortality ratio (SMR) method.

RESULTS: SMRs for both radiation and non-radiation workers had lower risks of death from all causes (0.74; 95% confidence interval [CI] 0.74 to 0.75 and 0.77; 95% Cl 0.77 to 0.78, respectively) and from all cancers (0.92; 95% CI 0.91 to 0.93 and 0.90; 95% CI 0.89 to 0.91, respectively) compared with US men. Asbestos-related diseases including pleural cancers, mesothelioma, and asbestosis, but not lung cancers, were statistically higher in both radiation and non-radiation workers compared with the US men.

CONCLUSION: US shipyard male radiation and non-radiation workers did not show any elevated mortality risks that might be associated with radiation exposure.}, } @article {pmid35078853, year = {2022}, author = {Kok, PS and Forde, PM and Hughes, B and Sun, Z and Brown, C and Ramalingam, S and Cook, A and Lesterhuis, WJ and Yip, S and O'Byrne, K and Pavlakis, N and Brahmer, J and Anagnostou, V and Ford, K and Fitzpatrick, K and Bricker, A and Cummins, MM and Stockler, M and Nowak, AK and , }, title = {Protocol of DREAM3R: DuRvalumab with chEmotherapy as first-line treAtment in advanced pleural Mesothelioma-a phase 3 randomised trial.}, journal = {BMJ open}, volume = {12}, number = {1}, pages = {e057663}, pmid = {35078853}, issn = {2044-6055}, mesh = {Adolescent ; Adult ; Aged ; Antibodies, Monoclonal ; Antineoplastic Combined Chemotherapy Protocols ; Clinical Trials, Phase III as Topic ; Humans ; *Lung Neoplasms/drug therapy ; *Mesothelioma/drug therapy/pathology ; *Mesothelioma, Malignant ; Middle Aged ; Multicenter Studies as Topic ; Quality of Life ; Randomized Controlled Trials as Topic ; Young Adult ; }, abstract = {INTRODUCTION: There is a strong theoretical rationale for combining checkpoint blockade with cytotoxic chemotherapy in pleural mesothelioma and other cancers. Two recent single-arm, phase 2 trials [DuRvalumab with chEmotherapy as first-line treAtment in advanced pleural Mesothelioma (DREAM) and Phase II multicenter study of anti-PD-L1, durvalumab, in combination with cisplatin and pemetrexed for the first-line treatment of unresectable malignant pleural mesothelioma (PrE0505)] combining the programmed death ligand-1 (PD-L1) inhibitor durvalumab with standard first-line chemotherapy exceeded prespecified safety and activity criteria to proceed to a phase 3 confirmatory trial to assess this combination. We present the protocol of the DREAM3R trial.

METHODS AND ANALYSIS: This multicentre open-label randomised trial will recruit 480 treatment-naïve adults with advanced pleural mesothelioma, randomised (2:1) to either 3-weekly durvalumab 1500 mg plus 3-weekly doublet chemotherapy (cisplatin 75 mg/m[2] or carboplatin, Area Under the Curve,AUC 5 and pemetrexed 500 mg/m[2]) 4-6 cycles, followed by 4-weekly durvalumab 1500 mg until disease progression, unacceptable toxicity or patient withdrawal; OR doublet chemotherapy alone for 4-6 cycles, followed by observation. The target accrual time is 27 months, with follow-up for an additional 24 months. This provides over 85% power if the true HR for overall survival (OS) is 0.70, with two-sided alpha of 0.05, assuming a median OS of 15 months in the control group. Randomisation is stratified by age (18-70 years vs >70), sex, histology (epithelioid vs non-epithelioid), platinum agent (cisplatin vs carboplatin) and region (USA vs Australia/New Zealand vs Other). The primary endpoint is OS. Secondary endpoints include progression-free survival, objective tumour response (by mRECIST V.1.1 and iRECIST), adverse events, health-related quality of life and healthcare resource use. Tertiary correlative objectives are to explore and validate potential prognostic and/or predictive biomarkers (including features identified in the DuRvalumab with chEmotherapy as first-line treAtment in advanced pleural Mesothelioma (DREAM) and PrE0505 studies, PD-L1 expression, tumour mutational burden, genomic characteristics and human leukocyte antigen subtypes) in tissue and serial blood samples. An imaging databank will be assembled for validation of radiological measures of response, and studies of possible radiomic biomarkers in mesothelioma.

ETHICS AND DISSEMINATION: The protocol was approved by human research ethics review committees for all participating sites. Results will be disseminated in peer-reviewed journals and at scientific conferences.

DRUG SUPPLY: AstraZeneca.

PROTOCOL VERSION: CTC 0231 / TOGA 18/001 / PrE0506 3.0, 29 July 2021.

TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT04334759 ACTRN 12620001199909.}, } @article {pmid35073065, year = {2022}, author = {Voloaca, OM and Clench, MR and Koellensperger, G and Cole, LM and Haywood-Small, SL and Theiner, S}, title = {Elemental Mapping of Human Malignant Mesothelioma Tissue Samples Using High-Speed LA-ICP-TOFMS Imaging.}, journal = {Analytical chemistry}, volume = {94}, number = {5}, pages = {2597-2606}, pmid = {35073065}, issn = {1520-6882}, mesh = {*Asbestos/toxicity ; Humans ; *Laser Therapy ; Mass Spectrometry/methods ; *Mesothelioma, Malignant ; Spectrum Analysis ; }, abstract = {This is the first report of the use of laser ablation-inductively coupled plasma time-of-flight mass spectrometry (LA-ICP-TOFMS) to analyze human malignant pleural mesothelioma (MPM) samples at the cellular level. MPM is an aggressive, incurable cancer associated with asbestos exposure, with a long latency and poor overall survival. Following careful optimization of the laser fluence, the simultaneous ablation of soft biological tissue and hard mineral fibers was possible, allowing the spatial detection of elements such as Si, Mg, Ca, and Fe, which are also present in the glass substrate. A low-dispersion LA setup was employed, which provided the high spatial resolution necessary to identify the asbestos fibers and fiber fragments in the tissue and to characterize the metallome at the cellular level (a pixel size of 2 μm), with a high speed (at 250 Hz). The multielement LA-ICP-TOFMS imaging approach enabled (i) the detection of asbestos fibers/mineral impurities within the MPM tissue samples of patients, (ii) the visualization of the tissue structure with the endogenous elemental pattern at high spatial resolution, and (iii) obtaining insights into the metallome of MPM patients with different pathologies in a single analysis run. Asbestos and other mineral fibers were detected in the lung and pleura tissue of MPM patients, respectively, based on their multielement pattern (Si, Mg, Ca, Fe, and Sr). Interestingly, strontium was detected in asbestos fibers, suggesting a link between this potential toxic element and MPM pathogenesis. Furthermore, monitoring the metallome around the talc deposit regions (characterized by elevated levels of Al, Mg, and Si) revealed significant tissue damage and inflammation caused by talc pleurodesis. LA-ICP-TOFMS results correlated to Perls' Prussian blue and histological staining of the corresponding serial sections. Ultimately, the ultra-high-speed and high-spatial-resolution capabilities of this novel LA-ICP-TOFMS setup may become an important clinical tool for simultaneous asbestos detection, metallome monitoring, and biomarker identification.}, } @article {pmid35058235, year = {2022}, author = {Senek, M and Robertson, S and Darlison, L and Creech, L and Tod, A}, title = {Malignant pleural mesothelioma patients' experience by gender: findings from a cross-sectional UK-national questionnaire.}, journal = {BMJ open respiratory research}, volume = {9}, number = {1}, pages = {}, pmid = {35058235}, issn = {2052-4439}, mesh = {Cross-Sectional Studies ; Female ; Humans ; Male ; *Mesothelioma, Malignant ; Quality of Life ; Surveys and Questionnaires ; United Kingdom ; }, abstract = {OBJECTIVES: Malignant mesothelioma is an aggressive malignancy of mesothelial surfaces, most commonly those of the pleura. The aim of this study was to understand, using a national questionnaire, the gendered care experiences of patients with malignant pleural mesothelioma (MPM).Patients were asked about their experience of the diagnostic process, about information clarity, health care professionals' knowledge, general practitioner support and overall satisfaction with care received.

SETTING: Recruitment of patients was carried out in three UK countries (England, Wales and Scotland) via mesothelioma clinical nurse specialists.

PARTICIPANTS: In total, 503 patients completed the questionnaire. 460 had MPM, the remainder had other types of mesothelioma. In accord with the study protocol, only the MPM patients were included in this study.Primary and secondary measures were: (1) time from symptom to diagnosis, (2) satisfaction with the diagnosis and treatment, and (3) quality of life and well-being.

RESULTS: There were gender differences in time from symptom to diagnosis. The time from symptom to diagnosis was significantly longer for women than men (median=152 days vs men=92 days, p=0.01). Lack of a verified source of exposure to asbestos was a hindrance to private treatment access for women (95% of those that access private treatment are men). Patients were five times more likely to be satisfied if they thought that the doctors knew enough about their condition (OR=4.4, p=0.001) and nearly three times more likely to be satisfied if information was presented in a sensitive way (OR=2.8,p=0.01).

CONCLUSIONS: This study has several implications for clinical practice. Our findings suggest that the diagnostic time in women might be reduced by reviewing diagnostic processes including occupational history taking, and by revising the occupational risk of mesothelioma categorisation.}, } @article {pmid35042132, year = {2022}, author = {Armato, SG and Nowak, AK and Francis, RJ and Katz, SI and Kholmatov, M and Blyth, KG and Gudmundsson, E and Kidd, AC and Gill, RR}, title = {Imaging in pleural mesothelioma: A review of the 15th International Conference of the International Mesothelioma Interest Group.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {164}, number = {}, pages = {76-83}, doi = {10.1016/j.lungcan.2021.12.008}, pmid = {35042132}, issn = {1872-8332}, support = {R25 CA240134/CA/NCI NIH HHS/United States ; S10 RR021039/RR/NCRR NIH HHS/United States ; }, mesh = {Humans ; *Lung Neoplasms/pathology ; Magnetic Resonance Imaging ; *Mesothelioma/diagnostic imaging/pathology ; Neoplasm Staging ; *Pleural Neoplasms/diagnosis/pathology ; Public Opinion ; }, abstract = {Imaging of mesothelioma plays a role in all aspects of patient management, including disease detection, staging, evaluation of treatment options, response assessment, pre-surgical evaluation, and surveillance. Imaging in this disease impacts a wide range of disciplines throughout the healthcare enterprise. Researchers and clinician-scientists are developing state-of-the-art techniques to extract more of the information contained within these medical images and to utilize it for more sophisticated tasks; moreover, image-acquisition technology is advancing the inherent capabilities of these images. This paper summarizes the imaging-based topics presented orally at the 2021 International Conference of the International Mesothelioma Interest Group (iMig), which was held virtually from May 7-9, 2021. These topics include an update on the mesothelioma staging system, novel molecular targets to guide therapy in mesothelioma, special considerations and potential pitfalls in imaging mesothelioma in the immunotherapy setting, tumor measurement strategies and their correlation with patient survival, tumor volume measurement in MRI and CT, CT-based texture analysis for differentiation of histologic subtype, diffusion-weighted MRI for the assessment of biphasic mesothelioma, and the prognostic significance of skeletal muscle loss with chemotherapy.}, } @article {pmid35032816, year = {2022}, author = {Sculco, M and La Vecchia, M and Aspesi, A and Pinton, G and Clavenna, MG and Casalone, E and Allione, A and Grosso, F and Libener, R and Muzio, A and Rena, O and Baietto, G and Parini, S and Boldorini, R and Giachino, D and Papotti, M and Scagliotti, GV and Migliore, E and Mirabelli, D and Moro, L and Magnani, C and Ferrante, D and Matullo, G and Dianzani, I}, title = {Malignant pleural mesothelioma: Germline variants in DNA repair genes may steer tailored treatment.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {163}, number = {}, pages = {44-54}, doi = {10.1016/j.ejca.2021.12.023}, pmid = {35032816}, issn = {1879-0852}, mesh = {DNA Repair/genetics ; Germ Cells/pathology ; Humans ; *Lung Neoplasms/drug therapy/genetics/pathology ; *Mesothelioma/drug therapy/genetics/pathology ; *Mesothelioma, Malignant ; *Pleural Neoplasms/drug therapy/genetics/pathology ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is a tumour associated with asbestos exposure. Approximately, 10% of patients with MPM carry a germline pathogenic variant (PV), mostly in DNA repair genes, suggesting the occurrence of inherited predispositions.

AIM: This article aimed to 1) search for new predisposing genes and assess the prevalence of PVs in DNA repair genes, by next-generation sequencing (NGS) analysis of germline DNA from 113 unselected patients with MPM and 2) evaluate whether these patients could be sensitive to tailored treatments.

METHODS: NGS was performed using a custom panel of 107 cancer-predisposing genes. To investigate the response to selected drugs in conditions of DNA repair insufficiency, we created a three-dimensional-MPM cell model that had a defect in ataxia telangiectasia mutated (ATM), the master regulator of DNA repair.

RESULTS: We identified PVs in approximately 7% of patients with MPM (8/113) and a new PV in BAP1 in a further patient with familial MPM. Most of these PVs were in genes involved or supposedly involved in DNA repair (BRCA1, BRIP1, CHEK2, SLX4, FLCN and BAP1). In vitro studies showed apoptosis induction in ATM-silenced/inhibited MPM spheroids treated with an enhancer of zeste homologue 2 inhibitor (tazemetostat).

CONCLUSIONS: Overall these data suggest that patients with MPM and DNA repair insufficiency may benefit from this treatment, which induces synthetic lethality.}, } @article {pmid35010531, year = {2021}, author = {Dalsgaard, SB and Würtz, ET and Hansen, J and Røe, OD and Omland, Ø}, title = {Cancer Incidence and Risk of Multiple Cancers after Environmental Asbestos Exposure in Childhood-A Long-Term Register-Based Cohort Study.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {1}, pages = {}, pmid = {35010531}, issn = {1660-4601}, mesh = {*Asbestos/toxicity ; Child ; Cohort Studies ; Environmental Exposure/statistics & numerical data ; Humans ; Incidence ; *Mesothelioma/chemically induced/epidemiology ; *Occupational Diseases ; *Occupational Exposure/statistics & numerical data ; }, abstract = {OBJECTIVES: To examine the asbestos-associated cancer incidence and the risk of multiple cancers in former school children exposed to environmental asbestos in childhood.

METHODS: A cohort of 12,111 former school children, born 1940-1970, was established using 7th grade school records from four schools located at a distance of 100-750 m in the prevailing wind direction from a large asbestos-cement plant that operated from 1928 to 1984 in Aalborg, Denmark. Using the unique Danish personal identification number, we linked information on employments, relatives' employments, date of cancer diagnosis, and type of cancer and vital status to data on cohortees extracted from the Supplementary Pension Fund Register (employment history), the Danish Cancer Registry, and the Danish Civil Registration System. We calculated standardized incidence rates (SIRs) for asbestos-associated cancers, all cancers, and multiple cancers using rates for a gender and five-year frequency-matched reference cohort.

RESULTS: The overall incidence of cancer was modestly increased for the school cohort (SIR 1.07, 95% confidence interval (CI) 1.02-1.12) compared with the reference cohort. This excess was driven primarily by a significantly increased SIR for malignant mesothelioma (SIR 8.77, 95% CI 6.38-12.05). Former school children who had combined childhood environmental and subsequent occupational exposure to asbestos had a significantly increased risk of lung cancer. Within this group, those with additional household exposure by a relative had a significantly increased SIR for cancer of the pharynx (SIR 4.24, 95% CI 1.59-11.29). We found no significant difference in the number of subjects diagnosed with multiple cancers between the two cohorts.

CONCLUSIONS: Our study confirms the strong association between environmental asbestos exposure and malignant mesothelioma and suggests that environmental asbestos exposure in childhood may increase the overall cancer risk later in life.}, } @article {pmid35010496, year = {2021}, author = {Binazzi, A and Di Marzio, D and Verardo, M and Migliore, E and Benfatto, L and Malacarne, D and Mensi, C and Consonni, D and Eccher, S and Mazzoleni, G and Comiati, V and Negro, C and Romanelli, A and Chellini, E and Angelini, A and Grappasonni, I and Madeo, G and Romeo, E and Di Giammarco, A and Carrozza, F and Angelillo, IF and Cavone, D and Vimercati, L and Labianca, M and Tallarigo, F and Tumino, R and Melis, M and Bonafede, M and Scarselli, A and Marinaccio, A and On Behalf Of The ReNaM Working Group, }, title = {Asbestos Exposure and Malignant Mesothelioma in Construction Workers-Epidemiological Remarks by the Italian National Mesothelioma Registry (ReNaM).}, journal = {International journal of environmental research and public health}, volume = {19}, number = {1}, pages = {}, pmid = {35010496}, issn = {1660-4601}, mesh = {*Asbestos ; *Construction Industry ; Humans ; Italy/epidemiology ; *Mesothelioma/chemically induced/epidemiology ; *Mesothelioma, Malignant ; *Occupational Exposure ; Registries ; }, abstract = {Notwithstanding the ban in 1992, asbestos exposure for workers in the construction sector in Italy remains a concern. The purpose of this study is to describe the characteristics of malignant mesothelioma (MM) cases recorded by the Italian registry (ReNaM) among construction workers. Incident mesothelioma cases with a definite asbestos exposure have been analyzed. Characteristics of cases and territorial clusters of crude rates of MM in construction workers have been described, as well as the relation between asbestos use before the ban and the historical trend of workforce in the construction sector in Italy. ReNaM has collected 31,572 incident MM cases in the period from 1993 to 2018 and asbestos exposure has been assessed for 24,864 (78.2%) cases. An occupational exposure has been reported for 17,191 MM cases (69.1% of subjects with a definite asbestos exposure). Among them, 3574 had worked in the construction sector, with an increasing trend from 15.8% in the 1993-98 period to 23.9% in 2014-2018 and a ubiquitous territorial distribution. The large use of asbestos in construction sector before the ban makes probability of exposure for workers a real concern still today, particularly for those working in maintenance and removal of old buildings. There is a clear need to assess, inform, and prevent asbestos exposure in this sector.}, } @article {pmid35004305, year = {2021}, author = {Crovella, S and Revelant, A and Muraro, E and Moura, RR and Brandão, L and Trovò, M and Steffan, A and Zacchi, P and Zabucchi, G and Minatel, E and Borelli, V}, title = {Biological Pathways Associated With the Development of Pulmonary Toxicities in Mesothelioma Patients Treated With Radical Hemithoracic Radiation Therapy: A Preliminary Study.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {784081}, pmid = {35004305}, issn = {2234-943X}, abstract = {Radical hemithoracic radiotherapy (RHR), after lung-sparing surgery, has recently become a concrete therapeutic option for malignant pleural mesothelioma (MPM), an asbestos-related, highly aggressive tumor with increasing incidence and poor prognosis. Although the toxicity associated to this treatment has been reduced, it is still not negligible and must be considered when treating patients. Genetic factors appear to play a role determining radiotherapy toxicity. The aim of this study is the identification of biological pathways, retrieved through whole exome sequencing (WES), possibly associated to the development of lung adverse effects in MPM patients treated with RHR. The study included individuals with MPM, treated with lung-sparing surgery and chemotherapy, followed by RHR with curative intent, and followed up prospectively for development of pulmonary toxicity. Due to the strong impact of grade 3 pulmonary toxicities on the quality of life, compared with less serious adverse events, for genetic analyses, patients were divided into a none or tolerable pulmonary toxicity (NoSTox) group (grade ≤2) and a severe pulmonary toxicity (STox) group (grade = 3). Variant enrichment analysis allowed us to identify different pathway signatures characterizing NoSTox and Stox patients, allowing to formulate hypotheses on the protection from side effects derived from radiotherapy as well as factors predisposing to a worst response to the treatment. Our findings, being aware of the small number of patients analyzed, could be considered a starting point for the definition of a panel of pathways, possibly helpful in the management of MPM patients.}, } @article {pmid35001771, year = {2022}, author = {Korchevskiy, AA and Wylie, AG}, title = {Dimensional characteristics of the major types of amphibole mineral particles and the implications for carcinogenic risk assessment.}, journal = {Inhalation toxicology}, volume = {34}, number = {1-2}, pages = {24-38}, doi = {10.1080/08958378.2021.2024304}, pmid = {35001771}, issn = {1091-7691}, mesh = {Asbestos, Amphibole/analysis/toxicity ; Carcinogenesis ; Carcinogens/toxicity ; Humans ; *Lung Neoplasms/chemically induced ; *Mesothelioma/chemically induced ; Minerals/toxicity ; Risk Assessment ; }, abstract = {Context: Though some significant advances have been made in recent decades to evaluate the importance of size and morphology (habit) of elongate mineral particles (EMPs), further research is needed to better understand the role of each dimensional metric in determining the levels of cancer potency.Objective: To determine dimensional parameters most relevant for predicting cancer potency of durable elongate particles, specifically amphibole and durable silicate minerals generally.Methods: A database on dimensional and other relevant characteristics of elongate amphibole mineral particles was created, containing particle-by-particle information for 128 099 particles. Integral statistical characteristics on dimensionality of various amphibole types and morphological habits of EMPs were calculated, compared, and correlated with published mesothelioma and lung cancer potency factors.Results: The highest absolute Pearson correlation (r = 0.97, r[2] = 0.94, p < 0.05) was achieved between mesothelioma potency (RM) and specific surface area. The highest correlation with adjusted lung cancer potency was found with particle aspect ratio (AR) (r = 0.80, r[2] = 0.64, p < 0.05). Cluster analysis demonstrates that fractions of thin fibers (width less than 0.15 and 0.25 µm) also closely relate both to lung cancer and RM. Asbestiform and non-asbestiform populations of amphiboles significantly differ by dimensionality and carcinogenic potency.Conclusions: Dimensional parameters and morphological habits of EMPs are the main drivers for the observable difference in cancer potency among amphibole populations.}, } @article {pmid34992464, year = {2021}, author = {Tai, SY and Wu, J and Lee, LJ and Lu, TH}, title = {How Malignant Mesothelioma Was Coded in Mortality Data in Taiwan During Years When the Specific ICD Code Was Not Available?.}, journal = {Clinical epidemiology}, volume = {13}, number = {}, pages = {1135-1140}, pmid = {34992464}, issn = {1179-1349}, abstract = {PURPOSE: Malignant mesothelioma (MM) is associated with past exposure to asbestos and the latency period ranged from 20 to 40 years. Asbestos consumption reached a peak in the 1980s in Taiwan, and the MM mortality is expected to increase since 2000s. However, no specific code for MM was available before the International Classification of Disease, Tenth Revision (ICD-10), which was launched in 2008 in Taiwan. We examined how MM was coded in mortality data in Taiwan during the years when the ICD, Ninth Revision (ICD-9) was used.

PATIENTS AND METHODS: Double-coded mortality data (each death coded according to both ICD-10 and ICD-9 codes) for the period 2002-2008 were obtained for analysis. Detection rates (similar to sensitivity) and confirmation rates (similar to positive predictive value) for various potential proxy ICD-9 codes for MM were calculated.

RESULTS: For 113 deaths, for which the underlying cause of death was ICD-10 code C45 (MM), 14 corresponding ICD-9 codes were used. Four ICD-9 codes constituted 77% (87/113) of all MM deaths. The detection rate for code 199 (malignant neoplasm [MN] without specification of site) was 37% (42/113), that for code 163 (MN of pleura) was 18% (20/113), that for code 162 (MN of trachea, bronchus, and lung) was 12% (14/113), and that for code 173 (other MN of skin) was 10% (11/113). The confirmation rates for codes 199, 163, 162, and 173 were 0.9% (42/4759), 14.3% (20/140), 0.03% (14/51,778), and 1.5% (11/717), respectively.

CONCLUSION: ICD-9 codes 199, 163, 162, and 173 were most commonly used for MM deaths in Taiwan during the years before the ICD-10 introduction. However, when we used only ICD-9 code 163, which was most commonly used as a surrogate measure of MM in mortality studies during the ICD-9 era, we could detect only one-fifth of MM deaths in Taiwan.}, } @article {pmid34984327, year = {2022}, author = {Orozco Morales, ML and Rinaldi, CA and de Jong, E and Lansley, SM and Gummer, JPA and Olasz, B and Nambiar, S and Hope, DE and Casey, TH and Lee, YCG and Leslie, C and Nealon, G and Shackleford, DM and Powell, AK and Grimaldi, M and Balaguer, P and Zemek, RM and Bosco, A and Piggott, MJ and Vrielink, A and Lake, RA and Lesterhuis, WJ}, title = {PPARα and PPARγ activation is associated with pleural mesothelioma invasion but therapeutic inhibition is ineffective.}, journal = {iScience}, volume = {25}, number = {1}, pages = {103571}, pmid = {34984327}, issn = {2589-0042}, abstract = {Mesothelioma is a cancer that typically originates in the pleura of the lungs. It rapidly invades the surrounding tissues, causing pain and shortness of breath. We compared cell lines injected either subcutaneously or intrapleurally and found that only the latter resulted in invasive and rapid growth. Pleural tumors displayed a transcriptional signature consistent with increased activity of nuclear receptors PPARα and PPARγ and with an increased abundance of endogenous PPAR-activating ligands. We found that chemical probe GW6471 is a potent, dual PPARα/γ antagonist with anti-invasive and anti-proliferative activity in vitro. However, administration of GW6471 at doses that provided sustained plasma exposure levels sufficient for inhibition of PPARα/γ transcriptional activity did not result in significant anti-mesothelioma activity in mice. Lastly, we demonstrate that the in vitro anti-tumor effect of GW6471 is off-target. We conclude that dual PPARα/γ antagonism alone is not a viable treatment modality for mesothelioma.}, } @article {pmid34967848, year = {2022}, author = {, and Kocarnik, JM and Compton, K and Dean, FE and Fu, W and Gaw, BL and Harvey, JD and Henrikson, HJ and Lu, D and Pennini, A and Xu, R and Ababneh, E and Abbasi-Kangevari, M and Abbastabar, H and Abd-Elsalam, SM and Abdoli, A and Abedi, A and Abidi, H and Abolhassani, H and Adedeji, IA and Adnani, QES and Advani, SM and Afzal, MS and Aghaali, M and Ahinkorah, BO and Ahmad, S and Ahmad, T and Ahmadi, A and Ahmadi, S and Ahmed Rashid, T and Ahmed Salih, Y and Akalu, GT and Aklilu, A and Akram, T and Akunna, CJ and Al Hamad, H and Alahdab, F and Al-Aly, Z and Ali, S and Alimohamadi, Y and Alipour, V and Aljunid, SM and Alkhayyat, M and Almasi-Hashiani, A and Almasri, NA and Al-Maweri, SAA and Almustanyir, S and Alonso, N and Alvis-Guzman, N and Amu, H and Anbesu, EW and Ancuceanu, R and Ansari, F and Ansari-Moghaddam, A and Antwi, MH and Anvari, D and Anyasodor, AE and Aqeel, M and Arabloo, J and Arab-Zozani, M and Aremu, O and Ariffin, H and Aripov, T and Arshad, M and Artaman, A and Arulappan, J and Asemi, Z and Asghari Jafarabadi, M and Ashraf, T and Atorkey, P and Aujayeb, A and Ausloos, M and Awedew, AF and Ayala Quintanilla, BP and Ayenew, T and Azab, MA and Azadnajafabad, S and Azari Jafari, A and Azarian, G and Azzam, AY and Badiye, AD and Bahadory, S and Baig, AA and Baker, JL and Balakrishnan, S and Banach, M and Bärnighausen, TW and Barone-Adesi, F and Barra, F and Barrow, A and Behzadifar, M and Belgaumi, UI and Bezabhe, WMM and Bezabih, YM and Bhagat, DS and Bhagavathula, AS and Bhardwaj, N and Bhardwaj, P and Bhaskar, S and Bhattacharyya, K and Bhojaraja, VS and Bibi, S and Bijani, A and Biondi, A and Bisignano, C and Bjørge, T and Bleyer, A and Blyuss, O and Bolarinwa, OA and Bolla, SR and Braithwaite, D and Brar, A and Brenner, H and Bustamante-Teixeira, MT and Butt, NS and Butt, ZA and Caetano Dos Santos, FL and Cao, Y and Carreras, G and Catalá-López, F and Cembranel, F and Cerin, E and Cernigliaro, A and Chakinala, RC and Chattu, SK and Chattu, VK and Chaturvedi, P and Chimed-Ochir, O and Cho, DY and Christopher, DJ and Chu, DT and Chung, MT and Conde, J and Cortés, S and Cortesi, PA and Costa, VM and Cunha, AR and Dadras, O and Dagnew, AB and Dahlawi, SMA and Dai, X and Dandona, L and Dandona, R and Darwesh, AM and das Neves, J and De la Hoz, FP and Demis, AB and Denova-Gutiérrez, E and Dhamnetiya, D and Dhimal, ML and Dhimal, M and Dianatinasab, M and Diaz, D and Djalalinia, S and Do, HP and Doaei, S and Dorostkar, F and Dos Santos Figueiredo, FW and Driscoll, TR and Ebrahimi, H and Eftekharzadeh, S and El Tantawi, M and El-Abid, H and Elbarazi, I and Elhabashy, HR and Elhadi, M and El-Jaafary, SI and Eshrati, B and Eskandarieh, S and Esmaeilzadeh, F and Etemadi, A and Ezzikouri, S and Faisaluddin, M and Faraon, EJA and Fares, J and Farzadfar, F and Feroze, AH and Ferrero, S and Ferro Desideri, L and Filip, I and Fischer, F and Fisher, JL and Foroutan, M and Fukumoto, T and Gaal, PA and Gad, MM and Gadanya, MA and Gallus, S and Gaspar Fonseca, M and Getachew Obsa, A and Ghafourifard, M and Ghashghaee, A and Ghith, N and Gholamalizadeh, M and Gilani, SA and Ginindza, TG and Gizaw, ATT and Glasbey, JC and Golechha, M and Goleij, P and Gomez, RS and Gopalani, SV and Gorini, G and Goudarzi, H and Grosso, G and Gubari, MIM and Guerra, MR and Guha, A and Gunasekera, DS and Gupta, B and Gupta, VB and Gupta, VK and Gutiérrez, RA and Hafezi-Nejad, N and Haider, MR and Haj-Mirzaian, A and Halwani, R and Hamadeh, RR and Hameed, S and Hamidi, S and Hanif, A and Haque, S and Harlianto, NI and Haro, JM and Hasaballah, AI and Hassanipour, S and Hay, RJ and Hay, SI and Hayat, K and Heidari, G and Heidari, M and Herrera-Serna, BY and Herteliu, C and Hezam, K and Holla, R and Hossain, MM and Hossain, MBH and Hosseini, MS and Hosseini, M and Hosseinzadeh, M and Hostiuc, M and Hostiuc, S and Househ, M and Hsairi, M and Huang, J and Hugo, FN and Hussain, R and Hussein, NR and Hwang, BF and Iavicoli, I and Ibitoye, SE and Ida, F and Ikuta, KS and Ilesanmi, OS and Ilic, IM and Ilic, MD and Irham, LM and Islam, JY and Islam, RM and Islam, SMS and Ismail, NE and Isola, G and Iwagami, M and Jacob, L and Jain, V and Jakovljevic, MB and Javaheri, T and Jayaram, S and Jazayeri, SB and Jha, RP and Jonas, JB and Joo, T and Joseph, N and Joukar, F and Jürisson, M and Kabir, A and Kahrizi, D and Kalankesh, LR and Kalhor, R and Kaliyadan, F and Kalkonde, Y and Kamath, A and Kameran Al-Salihi, N and Kandel, H and Kapoor, N and Karch, A and Kasa, AS and Katikireddi, SV and Kauppila, JH and Kavetskyy, T and Kebede, SA and Keshavarz, P and Keykhaei, M and Khader, YS and Khalilov, R and Khan, G and Khan, M and Khan, MN and Khan, MAB and Khang, YH and Khater, AM and Khayamzadeh, M and Kim, GR and Kim, YJ and Kisa, A and Kisa, S and Kissimova-Skarbek, K and Kopec, JA and Koteeswaran, R and Koul, PA and Koulmane Laxminarayana, SL and Koyanagi, A and Kucuk Bicer, B and Kugbey, N and Kumar, GA and Kumar, N and Kumar, N and Kurmi, OP and Kutluk, T and La Vecchia, C and Lami, FH and Landires, I and Lauriola, P and Lee, SW and Lee, SWH and Lee, WC and Lee, YH and Leigh, J and Leong, E and Li, J and Li, MC and Liu, X and Loureiro, JA and Lunevicius, R and Magdy Abd El Razek, M and Majeed, A and Makki, A and Male, S and Malik, AA and Mansournia, MA and Martini, S and Masoumi, SZ and Mathur, P and McKee, M and Mehrotra, R and Mendoza, W and Menezes, RG and Mengesha, EW and Mesregah, MK and Mestrovic, T and Miao Jonasson, J and Miazgowski, B and Miazgowski, T and Michalek, IM and Miller, TR and Mirzaei, H and Mirzaei, HR and Misra, S and Mithra, P and Moghadaszadeh, M and Mohammad, KA and Mohammad, Y and Mohammadi, M and Mohammadi, SM and Mohammadian-Hafshejani, A and Mohammed, S and Moka, N and Mokdad, AH and Molokhia, M and Monasta, L and Moni, MA and Moosavi, MA and Moradi, Y and Moraga, P and Morgado-da-Costa, J and Morrison, SD and Mosapour, A and Mubarik, S and Mwanri, L and Nagarajan, AJ and Nagaraju, SP and Nagata, C and Naimzada, MD and Nangia, V and Naqvi, AA and Narasimha Swamy, S and Ndejjo, R and Nduaguba, SO and Negoi, I and Negru, SM and Neupane Kandel, S and Nguyen, CT and Nguyen, HLT and Niazi, RK and Nnaji, CA and Noor, NM and Nuñez-Samudio, V and Nzoputam, CI and Oancea, B and Ochir, C and Odukoya, OO and Ogbo, FA and Olagunju, AT and Olakunde, BO and Omar, E and Omar Bali, A and Omonisi, AEE and Ong, S and Onwujekwe, OE and Orru, H and Ortega-Altamirano, DV and Otstavnov, N and Otstavnov, SS and Owolabi, MO and P A, M and Padubidri, JR and Pakshir, K and Pana, A and Panagiotakos, D and Panda-Jonas, S and Pardhan, S and Park, EC and Park, EK and Pashazadeh Kan, F and Patel, HK and Patel, JR and Pati, S and Pattanshetty, SM and Paudel, U and Pereira, DM and Pereira, RB and Perianayagam, A and Pillay, JD and Pirouzpanah, S and Pishgar, F and Podder, I and Postma, MJ and Pourjafar, H and Prashant, A and Preotescu, L and Rabiee, M and Rabiee, N and Radfar, A and Radhakrishnan, RA and Radhakrishnan, V and Rafiee, A and Rahim, F and Rahimzadeh, S and Rahman, M and Rahman, MA and Rahmani, AM and Rajai, N and Rajesh, A and Rakovac, I and Ram, P and Ramezanzadeh, K and Ranabhat, K and Ranasinghe, P and Rao, CR and Rao, SJ and Rawassizadeh, R and Razeghinia, MS and Renzaho, AMN and Rezaei, N and Rezaei, N and Rezapour, A and Roberts, TJ and Rodriguez, JAB and Rohloff, P and Romoli, M and Ronfani, L and Roshandel, G and Rwegerera, GM and S, M and Sabour, S and Saddik, B and Saeed, U and Sahebkar, A and Sahoo, H and Salehi, S and Salem, MR and Salimzadeh, H and Samaei, M and Samy, AM and Sanabria, J and Sankararaman, S and Santric-Milicevic, MM and Sardiwalla, Y and Sarveazad, A and Sathian, B and Sawhney, M and Saylan, M and Schneider, IJC and Sekerija, M and Seylani, A and Shafaat, O and Shaghaghi, Z and Shaikh, MA and Shamsoddin, E and Shannawaz, M and Sharma, R and Sheikh, A and Sheikhbahaei, S and Shetty, A and Shetty, JK and Shetty, PH and Shibuya, K and Shirkoohi, R and Shivakumar, KM and Shivarov, V and Siabani, S and Siddappa Malleshappa, SK and Silva, DAS and Singh, JA and Sintayehu, Y and Skryabin, VY and Skryabina, AA and Soeberg, MJ and Sofi-Mahmudi, A and Sotoudeh, H and Steiropoulos, P and Straif, K and Subedi, R and Sufiyan, MB and Sultan, I and Sultana, S and Sur, D and Szerencsés, V and Szócska, M and Tabarés-Seisdedos, R and Tabuchi, T and Tadbiri, H and Taherkhani, A and Takahashi, K and Talaat, IM and Tan, KK and Tat, VY and Tedla, BAA and Tefera, YG and Tehrani-Banihashemi, A and Temsah, MH and Tesfay, FH and Tessema, GA and Thapar, R and Thavamani, A and Thoguluva Chandrasekar, V and Thomas, N and Tohidinik, HR and Touvier, M and Tovani-Palone, MR and Traini, E and Tran, BX and Tran, KB and Tran, MTN and Tripathy, JP and Tusa, BS and Ullah, I and Ullah, S and Umapathi, KK and Unnikrishnan, B and Upadhyay, E and Vacante, M and Vaezi, M and Valadan Tahbaz, S and Velazquez, DZ and Veroux, M and Violante, FS and Vlassov, V and Vo, B and Volovici, V and Vu, GT and Waheed, Y and Wamai, RG and Ward, P and Wen, YF and Westerman, R and Winkler, AS and Yadav, L and Yahyazadeh Jabbari, SH and Yang, L and Yaya, S and Yazie, TSY and Yeshaw, Y and Yonemoto, N and Younis, MZ and Yousefi, Z and Yu, C and Yuce, D and Yunusa, I and Zadnik, V and Zare, F and Zastrozhin, MS and Zastrozhina, A and Zhang, J and Zhong, C and Zhou, L and Zhu, C and Ziapour, A and Zimmermann, IR and Fitzmaurice, C and Murray, CJL and Force, LM}, title = {Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life Years for 29 Cancer Groups From 2010 to 2019: A Systematic Analysis for the Global Burden of Disease Study 2019.}, journal = {JAMA oncology}, volume = {8}, number = {3}, pages = {420-444}, pmid = {34967848}, issn = {2374-2445}, support = {001/WHO_/World Health Organization/International ; SCAF/15/02/CSO_/Chief Scientist Office/United Kingdom ; SPHSU17/CSO_/Chief Scientist Office/United Kingdom ; MC_UU_00022/2/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Disability-Adjusted Life Years ; *Global Burden of Disease ; Global Health ; Humans ; Incidence ; *Neoplasms/epidemiology ; Prevalence ; Quality-Adjusted Life Years ; Risk Factors ; }, abstract = {IMPORTANCE: The Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019) provided systematic estimates of incidence, morbidity, and mortality to inform local and international efforts toward reducing cancer burden.

OBJECTIVE: To estimate cancer burden and trends globally for 204 countries and territories and by Sociodemographic Index (SDI) quintiles from 2010 to 2019.

EVIDENCE REVIEW: The GBD 2019 estimation methods were used to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life years (DALYs) in 2019 and over the past decade. Estimates are also provided by quintiles of the SDI, a composite measure of educational attainment, income per capita, and total fertility rate for those younger than 25 years. Estimates include 95% uncertainty intervals (UIs).

FINDINGS: In 2019, there were an estimated 23.6 million (95% UI, 22.2-24.9 million) new cancer cases (17.2 million when excluding nonmelanoma skin cancer) and 10.0 million (95% UI, 9.36-10.6 million) cancer deaths globally, with an estimated 250 million (235-264 million) DALYs due to cancer. Since 2010, these represented a 26.3% (95% UI, 20.3%-32.3%) increase in new cases, a 20.9% (95% UI, 14.2%-27.6%) increase in deaths, and a 16.0% (95% UI, 9.3%-22.8%) increase in DALYs. Among 22 groups of diseases and injuries in the GBD 2019 study, cancer was second only to cardiovascular diseases for the number of deaths, years of life lost, and DALYs globally in 2019. Cancer burden differed across SDI quintiles. The proportion of years lived with disability that contributed to DALYs increased with SDI, ranging from 1.4% (1.1%-1.8%) in the low SDI quintile to 5.7% (4.2%-7.1%) in the high SDI quintile. While the high SDI quintile had the highest number of new cases in 2019, the middle SDI quintile had the highest number of cancer deaths and DALYs. From 2010 to 2019, the largest percentage increase in the numbers of cases and deaths occurred in the low and low-middle SDI quintiles.

CONCLUSIONS AND RELEVANCE: The results of this systematic analysis suggest that the global burden of cancer is substantial and growing, with burden differing by SDI. These results provide comprehensive and comparable estimates that can potentially inform efforts toward equitable cancer control around the world.}, } @article {pmid34965001, year = {2022}, author = {Okazaki, Y}, title = {Asbestos-induced mesothelial injury and carcinogenesis: Involvement of iron and reactive oxygen species.}, journal = {Pathology international}, volume = {72}, number = {2}, pages = {83-95}, doi = {10.1111/pin.13196}, pmid = {34965001}, issn = {1440-1827}, support = {JSPS KAKENHI 21K06968//Japan Society for the Promotion of Science/ ; //JSPS KAKENHI/ ; }, mesh = {Animals ; Asbestos/*adverse effects ; Asbestos, Crocidolite/adverse effects ; Carcinogenesis ; Cation Transport Proteins/genetics/metabolism ; Deferasirox/administration & dosage ; Humans ; Iron/*metabolism ; Iron Chelating Agents/administration & dosage ; Mesothelioma, Malignant/chemically induced/*pathology ; Mice ; Mice, Transgenic ; Mineral Fibers/*adverse effects ; Nanotubes, Carbon/*adverse effects ; Oxidative Stress ; Reactive Oxygen Species/*metabolism ; }, abstract = {Asbestos fibers have been used as an industrial and construction material worldwide due to their high durability and low production cost. Commercial usage of asbestos is currently prohibited in Japan; however, the risk of asbestos-induced malignant mesothelioma (MM) remains. According to epidemiological data, the onset of MM is estimated to occur after a latent period of 30-40 years from initial exposure to asbestos fibers; thus, the continuous increase in MM is a concern. To explore the molecular mechanisms of MM using animal models, iron saccharate with iron chelator-induced sarcomatoid mesothelioma (SM) revealed hallmarks of homozygous deletion of Cdkn2a/2b by aCGH and microRNA-199/214 by expression microarray. Oral treatment of iron chelation by deferasirox decreased the rate of high-grade SM. Moreover, phlebotomy delayed MM development in crocidolite-induced MM in rats. In Divalent metal transporter 1 (Dmt1) transgenic mice, MM development was delayed because of low reactive oxygen species (ROS) production. These results indicate the importance of iron and ROS in mesothelial carcinogenesis. The aims of this review focus on the pathogenesis of elongated mineral particles (EMPs), including asbestos fibers and multiwalled carbon nanotubes (MWCNTs) that share similar rod-like shapes in addition to the molecular mechanisms of MM development.}, } @article {pmid34962302, year = {2022}, author = {Kottek, M and Yuen, ML}, title = {Public health risks from asbestos cement roofing.}, journal = {American journal of industrial medicine}, volume = {65}, number = {3}, pages = {157-161}, pmid = {34962302}, issn = {1097-0274}, mesh = {*Asbestos/toxicity ; Construction Materials/toxicity ; Humans ; *Mesothelioma/epidemiology ; *Mesothelioma, Malignant ; *Occupational Exposure/adverse effects ; Public Health ; Weather ; }, abstract = {There is no identified risk-free threshold exposure to asbestos. Based on epidemiology and toxicology, asbestos fiber dimensions have been implicated in causing asbestos-related diseases. Phase-contrast microscopy provides only a limited index of exposure to fiber dimensions implicated in mesothelioma induction. Installed asbestos-containing materials (ACMs) create an ongoing risk of intense exposure during natural disasters and remodeling, along with low-level exposure arising from the continual emission of airborne asbestos into the environment arising from weathering of installed ACM. Epidemiological studies have demonstrated a risk of disease associated with proximity to asbestos cement roofing (ACR), while ongoing environmental emissions of asbestos from installed ACR have also been demonstrated. Owing to the limitations of the available data, a precautionary approach is warranted; asbestos-free roofing materials should be used in new construction and existing ACR should be removed at the earliest opportunity.}, } @article {pmid34960727, year = {2021}, author = {Forte, IM and Indovina, P and Montagnaro, S and Costa, A and Iannuzzi, CA and Capone, F and Camerlingo, R and Malfitano, AM and Pentimalli, F and Ferrara, G and Quintiliani, M and Portella, G and Giordano, A and Ciarcia, R}, title = {The Oncolytic Caprine Herpesvirus 1 (CpHV-1) Induces Apoptosis and Synergizes with Cisplatin in Mesothelioma Cell Lines: A New Potential Virotherapy Approach.}, journal = {Viruses}, volume = {13}, number = {12}, pages = {}, pmid = {34960727}, issn = {1999-4915}, mesh = {Antineoplastic Agents/*pharmacology ; *Apoptosis/drug effects ; Cell Line, Tumor ; Cell Survival/drug effects ; Cisplatin/*pharmacology ; Combined Modality Therapy ; Humans ; Mesothelioma, Malignant/drug therapy/physiopathology/*therapy/virology ; *Oncolytic Virotherapy ; Oncolytic Viruses/genetics/*physiology ; Varicellovirus/genetics/*physiology ; }, abstract = {Malignant mesothelioma (MM) is an aggressive asbestos-related cancer, against which no curative modalities exist. Oncolytic virotherapy is a promising therapeutic approach, for which MM is an ideal candidate; indeed, the pleural location provides direct access for the intra-tumoral injection of oncolytic viruses (OVs). Some non-human OVs offer advantages over human OVs, including the non-pathogenicity in humans and the absence of pre-existing immunity. We previously showed that caprine herpesvirus 1 (CpHV-1), a non-pathogenic virus for humans, can kill different human cancer cell lines. Here, we assessed CpHV-1 effects on MM (NCI-H28, MSTO, NCI-H2052) and non-tumor mesothelial (MET-5A) cells. We found that CpHV-1 reduced cell viability and clonogenic potential in all MM cell lines without affecting non-tumor cells, in which, indeed, we did not detect intracellular viral DNA after treatment. In particular, CpHV-1 induced MM cell apoptosis and accumulation in G0/G1 or S cell cycle phases. Moreover, CpHV-1 strongly synergized with cisplatin, the drug currently used in MM chemotherapy, and this agent combination did not affect normal mesothelial cells. Although further studies are required to elucidate the mechanisms underlying the selective CpHV-1 action on MM cells, our data suggest that the CpHV-1-cisplatin combination could be a feasible strategy against MM.}, } @article {pmid34948918, year = {2021}, author = {Klebe, S and Hocking, AJ and Soeberg, M and Leigh, J}, title = {The Significance of Short Latency in Mesothelioma for Attribution of Causation: Report of a Case with Predisposing Germline Mutations and Review of the Literature.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {24}, pages = {}, pmid = {34948918}, issn = {1660-4601}, mesh = {*Asbestos/toxicity ; Germ-Line Mutation ; Humans ; *Lung Neoplasms/genetics ; Male ; *Mesothelioma/genetics ; *Mesothelioma, Malignant ; *Peritoneal Neoplasms/genetics ; }, abstract = {Malignant mesothelioma is a tumour of the serosal membranes, related to asbestos exposure. Median latency is in the order of 40 years in various registries, but small numbers of cases with shorter latencies have long been reported and often dismissed as unrelated to asbestos exposure. However, emerging data regarding the significance of inherited mutations leading to a predisposition to mesothelioma suggest that the causative effect of asbestos may be associated with shorter latencies in a subset of patients. Here, we describe a male patient with germline mutations in RAD51 and p53 who developed peritoneal mesothelioma 8.5 years after well-documented asbestos exposure and discuss the current literature on the subject. Mesothelioma in situ is now a WHO-accepted diagnosis, but preliminary data reveal a potential lead time of 5 or more years to invasive disease, and this is also a factor which may affect the recording of latency (and potentially survival) in the future.}, } @article {pmid34948906, year = {2021}, author = {Lysaniuk, B and Cely-García, MF and Giraldo, M and Larrahondo, JM and Serrano-Calderón, LM and Guerrero-Bernal, JC and Briceno-Ayala, L and Cruz Rodriguez, E and Ramos-Bonilla, JP}, title = {Using GIS to Estimate Population at Risk Because of Residence Proximity to Asbestos Processing Facilities in Colombia.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {24}, pages = {}, pmid = {34948906}, issn = {1660-4601}, mesh = {*Asbestos ; Asbestos, Serpentine ; Colombia/epidemiology ; Geographic Information Systems ; Humans ; *Mesothelioma ; Risk Factors ; }, abstract = {The recent enactment of the law banning asbestos in Colombia raises a significant number of challenges. The largest factories that have historically processed asbestos include five asbestos-cement facilities located in the cities of Sibaté (Cundinamarca), Cali (Valle del Cauca), and Barranquilla (Atlántico), and Manizales (Caldas), which has two, as well as a friction products facility in Bogotá D.C. An asbestos chrysotile mine has also operated in Colombia since 1980 in Campamento (Antioquia). In the framework of developing the National Asbestos Profile for Colombia, in this study, we estimated the population residing in the vicinity of asbestos processing plants or the mine and, therefore, potentially at risk of disease. Using a geographic information system, demographic data obtained from the last two general population censuses were processed to determine the number of people living within the concentric circles surrounding the asbestos facilities and the mine. In previous studies conducted in different countries of the world, an increased risk of asbestos-related diseases has been reported for people living at different distance bands from asbestos processing facilities. Based on these studies, circles of 500, 1000, 2000, 5000, and 10,000 m radii, centered on the asbestos processing facilities and the mine that operated in Colombia, were combined with the census data to estimate the number of people living within these radii. Large numbers of people were identified. It is estimated that in 2005, at the country level, 10,489 people lived within 500 m of an asbestos processing facility or mine. In 2018, and within a distance of 10,000 m, the number of people was 6,724,677. This information can aid public health surveillance strategies.}, } @article {pmid34944051, year = {2021}, author = {Abukar, A and Wipplinger, M and Hariharan, A and Sun, S and Ronner, M and Sculco, M and Okonska, A and Kresoja-Rakic, J and Rehrauer, H and Qi, W and Beusechem, VWV and Felley-Bosco, E}, title = {Double-Stranded RNA Structural Elements Holding the Key to Translational Regulation in Cancer: The Case of Editing in RNA-Binding Motif Protein 8A.}, journal = {Cells}, volume = {10}, number = {12}, pages = {}, pmid = {34944051}, issn = {2073-4409}, support = {320030_182690/SNSF_/Swiss National Science Foundation/Switzerland ; }, mesh = {3' Untranslated Regions/genetics ; Adenosine Deaminase/metabolism ; Animals ; Cell Line, Tumor ; Epithelium/metabolism ; Genes, Reporter ; Humans ; Mesothelioma/genetics/metabolism/pathology ; Mice ; Models, Biological ; Protein Binding ; *Protein Biosynthesis ; *RNA Editing ; RNA, Double-Stranded/*chemistry ; *RNA-Binding Motifs ; RNA-Binding Proteins/*metabolism ; }, abstract = {Mesothelioma is an aggressive cancer associated with asbestos exposure. RNA-binding motif protein 8a (RBM8A) mRNA editing increases in mouse tissues upon asbestos exposure. The aim of this study was to further characterize the role of RBM8A in mesothelioma and the consequences of its mRNA editing. RBM8A protein expression was higher in mesothelioma compared to mesothelial cells. Silencing RBM8A changed splicing patterns in mesothelial and mesothelioma cells but drastically reduced viability only in mesothelioma cells. In the tissues of asbestos-exposed mice, editing of Rbm8a mRNA was associated with increased protein immunoreactivity, with no change in mRNA levels. Increased adenosine deaminase acting on dsRNA (ADAR)-dependent editing of Alu elements in the RBM8A 3'UTR was observed in mesothelioma cells compared to mesothelial cells. Editing stabilized protein expression. The unedited RBM8A 3'UTR had a stronger interaction with Musashi (MSI) compared to the edited form. The silencing of MSI2 in mesothelioma or overexpression of Adar2 in mesothelial cells resulted in increased RBM8A protein levels. Therefore, ADAR-dependent editing contributes to maintaining elevated RBM8A protein levels in mesothelioma by counteracting MSI2-driven downregulation. A wider implication of this mechanism for the translational control of protein expression is suggested by the editing of similarly structured Alu elements in several other transcripts.}, } @article {pmid34943522, year = {2021}, author = {Gharib, AF and Alaa Eldeen, M and Khalifa, AS and Elsawy, WH and Eed, EM and Askary, AE and Eid, RA and Soltan, MA and Raafat, N}, title = {Assessment of Glutathione Peroxidase-1 (GPX1) Gene Expression as a Specific Diagnostic and Prognostic Biomarker in Malignant Pleural Mesothelioma.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {11}, number = {12}, pages = {}, pmid = {34943522}, issn = {2075-4418}, support = {TURSP-2020/157//Taif University/ ; }, abstract = {Malignant pleural mesothelioma (MPM) is a malignant tumor of the mesothelial lining of the thorax. It has been related to frequent exposure to asbestos. Diagnosis of malignant pleural mesothelioma is considered a criticizing problem for clinicians. Early diagnosis and sufficient surgical excision of MPM are considered the cornerstone success factors for the management of early MPM. Glutathione peroxidase-1 (GPX1) is an intracellular protein found to be extensively distributed in all cells, and it belongs to the GPX group. In the current study, we included ninety-eight patients with MPM that underwent surgery at the Zagazig University Hospital in Egypt. We assessed GPX1 gene expression level as it was thought to be related to pathogenicity of cancer in a variety of malignant tumors. We observed a significant elevation in GPX1-mRNA levels in MPM relative to the nearby normal pleural tissues. It was found to be of important diagnostic specificity in the differentiation of MPM from normal tissues. Moreover, we studied the survival of patients in correlation to the GPX1 expression levels and we reported that median overall survival was about 16 months in patients with high GPX1 expression levels, while it was found to be about 40 months in low GPX1 levels.}, } @article {pmid34909922, year = {2021}, author = {Hajj, GNM and Cavarson, CH and Pinto, CAL and Venturi, G and Navarro, JR and Lima, VCC}, title = {Malignant pleural mesothelioma: an update.}, journal = {Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia}, volume = {47}, number = {6}, pages = {e20210129}, pmid = {34909922}, issn = {1806-3756}, mesh = {*Asbestos/toxicity ; Humans ; *Mesothelioma/therapy ; *Mesothelioma, Malignant ; Pleura ; *Pleural Neoplasms/diagnosis/therapy ; }, abstract = {Malignant mesotheliomas are rare types of cancers that affect the mesothelial surfaces, usually the pleura and peritoneum. They are associated with asbestos exposure, but due to a latency period of more than 30 years and difficult diagnosis, most cases are not detected until they reach advanced stages. Treatment options for this tumor type are very limited and survival ranges from 12 to 36 months. This review discusses the molecular physiopathology, current diagnosis, and latest therapeutic options for this disease.}, } @article {pmid34907223, year = {2021}, author = {Frontini, F and Bononi, I and Torreggiani, E and Di Mauro, G and Mazzoni, E and Stendardo, M and Boschetto, P and Libener, R and Guaschino, R and Grosso, F and Guerra, G and Martini, F and Tognon, M}, title = {Circulating microRNA-197-3p as a potential biomarker for asbestos exposure.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {23955}, pmid = {34907223}, issn = {2045-2322}, mesh = {Aged ; Asbestos/*toxicity ; Biomarkers/blood ; Circulating MicroRNA/*blood/genetics ; Female ; Humans ; Male ; MicroRNAs/*blood/genetics ; Middle Aged ; Occupational Exposure/*adverse effects ; }, abstract = {Asbestos is considered the main cause of diseases in workers exposed to this mineral in the workplace as well as an environmental pollutant. The association between asbestos and the onset of different diseases has been reported, but asbestos exposure specific biomarkers are not known. MicroRNAs (miRNAs) are small, single-strand, non-coding RNAs, with potential value as diagnostic, prognostic, and predictive markers in liquid biopsies. Sera collected from workers ex-exposed to asbestos (WEA) fibers were compared with sera from healthy subjects (HS) of similar age, as liquid biopsies. The expression of the circulating miRNA 197-3p was investigated employing two different highly analytical PCR methods, i.e. RT-qPCR and ddPCR. MiR-197-3p levels were tested in sera from WEA compared to HS. MiR-197-3p tested dysregulated in sera from WEA (n = 75) compared to HS (n = 62). Indeed, miR-197-3p was found to be 2.6 times down-regulated in WEA vs. HS (p = 0.0001***). In addition, an inverse correlation was detected between miR-197-3p expression level and cumulative asbestos exposure, being this miRNA down-regulated 2.1 times in WEA, with high cumulative asbestos exposure, compared to WEA with low exposure (p = 0.0303*). Circulating miR-197-3p, found to be down regulated in sera from WEA, is proposed as a new potential biomarker of asbestos exposure.}, } @article {pmid34900693, year = {2021}, author = {Johnson, BW and Takahashi, K and Cheng, YY}, title = {Preclinical Models and Resources to Facilitate Basic Science Research on Malignant Mesothelioma - A Review.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {748444}, pmid = {34900693}, issn = {2234-943X}, abstract = {Malignant mesothelioma is an aggressive cancer with poor prognosis, predominantly caused by human occupational exposure to asbestos. The global incidence of mesothelioma is predicted to increase as a consequence of continued exposure to asbestos from a variety of sources, including construction material produced in the past in developed countries, as well as those currently being produced in developing countries. Mesothelioma typically develops after a long latency period and consequently it is often diagnosed in the clinic at an advanced stage, at which point standard care of treatment, such as chemo- and radio-therapy, are largely ineffective. Much of our current understanding of mesothelioma biology, particularly in relation to disease pathogenesis, diagnosis and treatment, can be attributed to decades of preclinical basic science research. Given the postulated rising incidence in mesothelioma cases and the limitations of current diagnostic and treatment options, continued preclinical research into mesothelioma is urgently needed. The ever-evolving landscape of preclinical models and laboratory technology available to researchers have made it possible to study human disease with greater precision and at an accelerated rate. In this review article we provide an overview of the various resources that can be exploited to facilitate an enhanced understanding of mesothelioma biology and their applications to research aimed to improve the diagnosis and treatment of mesothelioma. These resources include cell lines, animal models, mesothelioma-specific biobanks and modern laboratory techniques/technologies. Given that different preclinical models and laboratory technologies have varying limitations and applications, they must be selected carefully with respect to the intended objectives of the experiments. This review therefore aims to provide a comprehensive overview of the various preclinical models and technologies with respect to their advantages and limitations. Finally, we will detail about a highly valuable preclinical laboratory resource to curate high quality mesothelioma biospecimens for research; the biobank. Collectively, these resources are essential to the continued advancement of precision medicine to curtail the increasing health burden caused by malignant mesothelioma.}, } @article {pmid34898002, year = {2022}, author = {Marazioti, A and Krontira, AC and Behrend, SJ and Giotopoulou, GA and Ntaliarda, G and Blanquart, C and Bayram, H and Iliopoulou, M and Vreka, M and Trassl, L and Pepe, MAA and Hackl, CM and Klotz, LV and Weiss, SAI and Koch, I and Lindner, M and Hatz, RA and Behr, J and Wagner, DE and Papadaki, H and Antimisiaris, SG and Jean, D and Deshayes, S and Grégoire, M and Kayalar, Ö and Mortazavi, D and Dilege, Ş and Tanju, S and Erus, S and Yavuz, Ö and Bulutay, P and Fırat, P and Psallidas, I and Spella, M and Giopanou, I and Lilis, I and Lamort, AS and Stathopoulos, GT}, title = {KRAS signaling in malignant pleural mesothelioma.}, journal = {EMBO molecular medicine}, volume = {14}, number = {2}, pages = {e13631}, pmid = {34898002}, issn = {1757-4684}, mesh = {Animals ; Humans ; *Lung Neoplasms/genetics/pathology ; *Mesothelioma/genetics/pathology ; *Mesothelioma, Malignant/genetics/pathology ; Mice ; *Pleural Neoplasms/genetics/pathology ; *Proto-Oncogene Proteins p21(ras)/genetics/metabolism ; Signal Transduction ; Tumor Suppressor Proteins/genetics/metabolism ; Ubiquitin Thiolesterase/genetics/metabolism ; }, abstract = {Malignant pleural mesothelioma (MPM) arises from mesothelial cells lining the pleural cavity of asbestos-exposed individuals and rapidly leads to death. MPM harbors loss-of-function mutations in BAP1, NF2, CDKN2A, and TP53, but isolated deletion of these genes alone in mice does not cause MPM and mouse models of the disease are sparse. Here, we show that a proportion of human MPM harbor point mutations, copy number alterations, and overexpression of KRAS with or without TP53 changes. These are likely pathogenic, since ectopic expression of mutant KRAS[G12D] in the pleural mesothelium of conditional mice causes epithelioid MPM and cooperates with TP53 deletion to drive a more aggressive disease form with biphasic features and pleural effusions. Murine MPM cell lines derived from these tumors carry the initiating KRAS[G12D] lesions, secondary Bap1 alterations, and human MPM-like gene expression profiles. Moreover, they are transplantable and actionable by KRAS inhibition. Our results indicate that KRAS alterations alone or in accomplice with TP53 alterations likely play an important and underestimated role in a proportion of patients with MPM, which warrants further exploration.}, } @article {pmid34874752, year = {2021}, author = {Sohn, EJ}, title = {Bioinformatic Analysis of Potential Biomarker for hsa-miR-196b-5p in Mesothelioma.}, journal = {Genetic testing and molecular biomarkers}, volume = {25}, number = {12}, pages = {772-780}, doi = {10.1089/gtmb.2021.0147}, pmid = {34874752}, issn = {1945-0257}, mesh = {Biomarkers ; Cell Line, Tumor ; Computational Biology ; Humans ; *Mesothelioma/drug therapy/genetics ; *Mesothelioma, Malignant/genetics ; MicroRNAs/genetics/metabolism/*supply & distribution ; }, abstract = {Purpose: Malignant pleural mesothelioma is a rare neoplasia with a poor prognosis, and the majority of patients have advanced disease at the time of presentation. Exposure to asbestos is the most important risk factor for malignant pleural mesothelioma. Materials and Methods: To determine the cytotoxicity of geldanamycin in mesothelioma H28 cells, the MTT assay was used. To determine changes in microRNA (miRNA) expression in geldanamycin-treated H28 cells, miRNA microarray analysis was performed. To determine the function of miR-196b-5p, we performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of miR-196b-5p targets predicted by miRwalk. Results: Our data showed that geldanamycin treatment reduced H28 cell viability in a dose-dependent manner. MicroRNA array analyses showed that expression of hsa-miR-196b-5p was downregulated in geldanamycin-treated H28 cells. Geldanamycin regulated miRNAs with roles in processes such as aging, angiogenesis, apoptosis, cell cycle, cell differentiation, cell proliferation, DNA repair, and secretion. Survival analysis showed that decreased expression of hsa-miR-196b-5p was significantly associated with a better outcome in mesothelioma patients. Expression of miR-196b-5p was also significantly associated with the developmental stages of mesothelioma. To narrow down the target genes of miR-196b-5p, we determined the overlap between the predicted target genes of miR-196b-5p and downregulated mRNAs in ovarian cancer based on the Gene Expression Omnibus dataset GSE12345. PDE1A, LAMA4, and PAPPA were identified as both miR-196b-5p targets and downregulated genes in GSE12345 and were thus considered targets of miR-196b-5p. Gene-miRNA expression correlation analysis showed that PDE1A, LAMA4, and PAPPA expression was negatively correlated with miR-196b-5p expression. Conclusions: We suggest that geldanamycin has potential for the treatment of mesothelioma via regulating miR-196b-5p. Furthermore, miR-196b-5p may be a potential biomarker for mesothelioma.}, } @article {pmid34861373, year = {2022}, author = {Popat, S and Baas, P and Faivre-Finn, C and Girard, N and Nicholson, AG and Nowak, AK and Opitz, I and Scherpereel, A and Reck, M and , }, title = {Malignant pleural mesothelioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up[☆].}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {33}, number = {2}, pages = {129-142}, doi = {10.1016/j.annonc.2021.11.005}, pmid = {34861373}, issn = {1569-8041}, mesh = {Diagnosis, Differential ; Follow-Up Studies ; Humans ; *Lung Neoplasms/diagnosis/pathology/therapy ; *Mesothelioma/diagnosis/pathology/therapy ; *Mesothelioma, Malignant ; *Pleural Neoplasms/diagnosis/pathology/therapy ; }, } @article {pmid34843704, year = {2022}, author = {Chen, Z and Song, S and Yang, C and Dai, Z and Gao, Y and Li, N and Zhu, J and Mao, W and Liu, J}, title = {Lipid profiling in malignant mesothelioma reveals promising signatures for diagnosis and prognosis: A plasma-based LC-MS lipidomics study.}, journal = {Clinica chimica acta; international journal of clinical chemistry}, volume = {524}, number = {}, pages = {34-42}, doi = {10.1016/j.cca.2021.11.024}, pmid = {34843704}, issn = {1873-3492}, mesh = {Chromatography, Liquid ; Female ; Humans ; *Lipidomics ; Lipids ; Male ; *Mesothelioma, Malignant ; Tandem Mass Spectrometry ; }, abstract = {BACKGROUND AND AIM: Malignant mesothelioma (MM), being a rare and aggressive carcinoma, can barely be cured. Incidence of this cancer will keep climbing up in the next few decades since its major carcinogen, asbestos, is still in use in many countries. Unfortunately, prognosis of MM is unsatisfactory principally due to poor early diagnosis as a result of its long latency period and ambiguous symptoms. Lipids are known to contribute to cellular structure, signaling, and energy storage, and are widely reported to be related with tumorigenesis. Therefore, we aim to discover novel lipid biomarkers by plasma-based lipidomics that may improve MM diagnosis.

METHODS: Plasma samples from 25 MM patients and 32 healthy controls (HCs) were collected and analysed using a high-throughput liquid chromatography-mass spectrometry (LC-MS). Univariate and multivariate analyses were subsequently performed to visualize the separation trend between two groups and to screen for differential feature ions. Ions were annotated using LipidSearch 4.2 and their enriched pathways were detected on LIPEA. Receiver operating characteristic (ROC) curves were used for analysing each annotated lipid's diagnostic value. Survival analyses were performed to investigate each lipid's prognostic value.

RESULTS: In supervised partial least squares discriminant analysis (PLS-DA), clear separation between MM and HC groups was observed. A total of 34 differential lipids were annotated, among which 5 upregulated and 29 downregulated. Levels of plasma triacylglycerols (TGs) were higher in smoking versus non-smoking patients, and lower in female versus male patients. The top six lipids possessing highest diagnostic value included two phosphatidylethanolamines (PEs), two phosphatidylcholines (PCs) and two ceramides. Moreover, elevated circulating TG levels were associated with poorer survival, whereas increased monohexosylceramide (Hex1Cer) might be beneficial.

CONCLUSIONS: Our study revealed differentially expressed lipid patterns in MM compared to HC. PC, PE, and ceramides showed outstanding diagnostic performance, while TG and Hex1Cer exhibited significant prognostic values. Nevertheless, more studies should verify these trends as well as further investigating on underlying mechanisms.}, } @article {pmid34841838, year = {2021}, author = {De Sario, M and Bauleo, L and Magnani, C and Ferrante, D and Marinaccio, A and Michelozzi, P and Romeo, E}, title = {L'impatto dell'esposizione occupazionale ad amianto sul tumore del polmone in Italia.}, journal = {Epidemiologia e prevenzione}, volume = {45}, number = {5}, pages = {353-367}, doi = {10.19191/EP21.5.P353.102}, pmid = {34841838}, issn = {1120-9763}, mesh = {*Asbestos/toxicity ; Female ; Humans ; Italy/epidemiology ; *Lung Neoplasms ; Male ; *Mesothelioma/etiology ; *Occupational Diseases/epidemiology ; *Occupational Exposure/adverse effects ; *Pleural Neoplasms/epidemiology/etiology ; }, abstract = {OBJECTIVES: to perform a meta-analysis of cohort studies on lung cancer mortality in occupational sectors exposed to asbestos, particularly in the construction sector, and to use data from Italian cohorts exposed to asbestos to estimate the number of lung cancer cases attributable to asbestos in Italy.

METHODS: systematic literature review and estimation of lung cancer deaths and cases attributable to asbestos in Italian cohorts and from the Italian National Register of Malignant Mesothelioma (ReNaM).

SETTING AND PARTICIPANTS: the literature search was conducted in Medline and Embase (Ovid), including papers published from 1999 to May 2019. The following sectors were considered most exposed to asbestos: asbestos-cement, rolling-stock, shipyards, dockyards, glass workers, insulators, asphalt roll production workers, industrial ovens, miners. Moreover, the construction sector was included.

MAIN OUTCOME MEASURES: the standardized mortality ratio (SMR) was estimated from the meta-analysis of the literature review. The ratio lung cancer to mesothelioma attributable cases was estimated by occupational sector from the Italian cohorts. For the construction sector, the ratio lung cancer to mesothelioma cases was estimated within the exposed workers estimated by CAREX (1990-1993). The ratios were applied to the mesothelioma cases registered at the ReNaM for the 2010-2015 period, to obtain a national estimate of lung cancer cases attributable to occupational exposure to asbestos.

RESULTS: the meta-analytical SMR for lung cancer in men varied between 1.05 (asphalt roll) and 2.36 (insulation). The mean risk for all sectors was 1.37 in men and 1.60 in women. It increased in cohorts with latency higher than 20 years. Significant risks were observed in asbestos-cement (both genders), construction, and mining sectors. There was a mean of 1.1, 2.7, and 2.8 lung cancer deaths per mesothelioma death in the cement-asbestos, harbour, and construction sectors, respectively. The impact in terms of lung cancer cases estimated at the national level was equal to 3,814 cases between 2010 and 2015.

CONCLUSIONS: to provide an overall assessment of the impact of the occupational asbestos exposure, it is important to consider lung cancer cases, in addition to malignant mesotheliomas. This study was able to estimate the impact of asbestos on lung cancer in Italy 25 years after the ban of this occupational carcinogen, with the largest contribution in terms of attributable cases coming from the construction sector. It is urgent to implement adequate information and prevention strategies, health surveillance of workers, and the appropriate legal framework for insurance purposes.}, } @article {pmid34840219, year = {2023}, author = {Kawamoto, Y and Kure, S and Katayama, H and Kawahara, K and Teduka, K and Kunugi, S and Onda, M and Motoda, N and Ohashi, R}, title = {Cytological Assessment of Desmoplastic Malignant Pleural Mesothelioma in an Autopsy Case.}, journal = {Journal of Nippon Medical School = Nippon Ika Daigaku zasshi}, volume = {89}, number = {6}, pages = {616-622}, doi = {10.1272/jnms.JNMS.2022_89-605}, pmid = {34840219}, issn = {1347-3409}, mesh = {Humans ; Male ; Autopsy ; In Situ Hybridization, Fluorescence ; *Mesothelioma/diagnosis ; *Mesothelioma, Malignant/complications ; *Pleural Effusion/complications/pathology ; *Pleural Effusion, Malignant/complications/pathology ; *Pleural Neoplasms/diagnosis ; Middle Aged ; }, abstract = {INTRODUCTION: Desmoplastic malignant pleural mesothelioma (DMPM) is a sarcoma-type mesothelioma, comprising approximately 5% of malignant pleural mesotheliomas. Although effusion cytology is commonly used as the primary diagnostic approach for mesothelioma, it may not be useful for DMPM because of the presence of desmoplasia and bland cellular atypia. We report a case, and previously undescribed cytological features, of DMPM that was diagnosed during autopsy.

CASE PRESENTATION: A man in his 60s with a history of occupational asbestos exposure was referred to our hospital with right chest pain. A chest CT scan showed right pleural effusion. Thirteen months later, the patient died of respiratory failure. During autopsy, scrape-imprint smears were prepared and cytology of pleural effusions was performed. The scrape-imprint smear samples showed spindle cells with mild nuclear atypia and grooves with fibrous stroma. Pleural effusion cytology revealed spindle cells with mild nuclear atypia, as well as grooves with loose epithelial connections. Histological examination of the right pleura showed spindle cells proliferating with dense collagen fibers, as seen in the cytological samples, thus indicating a diagnosis of DMPM, which was confirmed by fluorescence in situ hybridization.

CONCLUSION: Cytological procedures such as pleural effusion cytology and scrape-imprinting cytology may help in diagnosing rare tumors such as DMPM.}, } @article {pmid34836499, year = {2021}, author = {Kelarji, AB and Alshutaihi, MS and Ghazal, A and Mahli, N and Agha, S}, title = {Correction to: A rare case of benign multicystic peritoneal mesothelioma misdiagnosed as hydatid cyst found in the liver parenchyma and abdomen cavity of a male with asbestos exposure.}, journal = {BMC gastroenterology}, volume = {21}, number = {1}, pages = {447}, pmid = {34836499}, issn = {1471-230X}, } @article {pmid34834557, year = {2021}, author = {Filetti, V and Loreto, C and Falzone, L and Lombardo, C and Cannizzaro, E and Castorina, S and Ledda, C and Rapisarda, V}, title = {Diagnostic and Prognostic Value of Three microRNAs in Environmental Asbestiform Fibers-Associated Malignant Mesothelioma.}, journal = {Journal of personalized medicine}, volume = {11}, number = {11}, pages = {}, pmid = {34834557}, issn = {2075-4426}, abstract = {Fluoro-edenite (FE) is an asbestiform fiber identified in Biancavilla (Sicily, Italy). Environmental exposure to FE has been associated with a higher incidence of malignant mesothelioma (MM). The present study aimed to validate the predicted diagnostic significance of hsa-miR-323a-3p, hsa-miR-101-3p, and hsa-miR-20b-5p on a subset of MM patients exposed to FE and matched with healthy controls. For this purpose, MM tissues vs. nonmalignant pleura tissues were analyzed through droplet digital PCR (ddPCR) to evaluate differences in the expression levels of the selected miRNAs and their MM diagnostic potential. In addition, further computational analysis has been performed to establish the correlation of these miRNAs with the available online asbestos exposure data and clinic-pathological parameters to verify the potential role of these miRNAs as prognostic tools. ddPCR results showed that the three analyzed miRNAs were significantly down-regulated in MM cases vs. controls. Receiver operating characteristic (ROC) analysis revealed high specificity and sensitivity rates for both hsa-miR-323a-3p and hsa-miR-20b-5p, which thus acquire a diagnostic value for MM. In silico results showed a potential prognostic role of hsa-miR-101-3p due to a significant association of its higher expression and increased overall survival (OS) of MM patients.}, } @article {pmid34830817, year = {2021}, author = {Cersosimo, F and Barbarino, M and Lonardi, S and Vermi, W and Giordano, A and Bellan, C and Giurisato, E}, title = {Mesothelioma Malignancy and the Microenvironment: Molecular Mechanisms.}, journal = {Cancers}, volume = {13}, number = {22}, pages = {}, pmid = {34830817}, issn = {2072-6694}, abstract = {Several studies have reported that cellular and soluble components of the tumor microenvironment (TME) play a key role in cancer-initiation and progression. Considering the relevance and the complexity of TME in cancer biology, recent research has focused on the investigation of the TME content, in terms of players and informational exchange. Understanding the crosstalk between tumor and non-tumor cells is crucial to design more beneficial anti-cancer therapeutic strategies. Malignant pleural mesothelioma (MPM) is a complex and heterogenous tumor mainly caused by asbestos exposure with few treatment options and low life expectancy after standard therapy. MPM leukocyte infiltration is rich in macrophages. Given the failure of macrophages to eliminate asbestos fibers, these immune cells accumulate in pleural cavity leading to the establishment of a unique inflammatory environment and to the malignant transformation of mesothelial cells. In this inflammatory landscape, stromal and immune cells play a driven role to support tumor development and progression via a bidirectional communication with tumor cells. Characterization of the MPM microenvironment (MPM-ME) may be useful to understand the complexity of mesothelioma biology, such as to identify new molecular druggable targets, with the aim to improve the outcome of the disease. In this review, we summarize the known evidence about the MPM-ME network, including its prognostic and therapeutic relevance.}, } @article {pmid34830097, year = {2021}, author = {Ramundo, V and Zanirato, G and Aldieri, E}, title = {The Epithelial-to-Mesenchymal Transition (EMT) in the Development and Metastasis of Malignant Pleural Mesothelioma.}, journal = {International journal of molecular sciences}, volume = {22}, number = {22}, pages = {}, pmid = {34830097}, issn = {1422-0067}, mesh = {Biomarkers, Tumor/metabolism ; *Epithelial-Mesenchymal Transition ; Humans ; Mesothelioma, Malignant/*metabolism/pathology/therapy ; MicroRNAs/metabolism ; Neoplasm Metastasis ; Neoplasm Proteins/metabolism ; Pleural Neoplasms/*metabolism/pathology/therapy ; RNA, Neoplasm/metabolism ; Transforming Growth Factor beta/metabolism ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive tumor mainly associated with asbestos exposure and is characterized by a very difficult pharmacological approach. One of the molecular mechanisms associated with cancer onset and invasiveness is the epithelial-to-mesenchymal transition (EMT), an event induced by different types of inducers, such as transforming growth factor β (TGFβ), the main inducer of EMT, and oxidative stress. MPM development and metastasis have been correlated to EMT; On one hand, EMT mediates the effects exerted by asbestos fibers in the mesothelium, particularly via increased oxidative stress and TGFβ levels evoked by asbestos exposure, thus promoting a malignant phenotype, and on the other hand, MPM acquires invasiveness via the EMT event, as shown by an upregulation of mesenchymal markers or, although indirectly, some miRNAs or non-coding RNAs, all demonstrated to be involved in cancer onset and metastasis. This review aims to better describe how EMT is involved in driving the development and invasiveness of MPM, in an attempt to open new scenarios that are useful in the identification of predictive markers and to improve the pharmacological approach against this aggressive cancer.}, } @article {pmid34827604, year = {2021}, author = {Javadi, J and Görgens, A and Vanky, H and Gupta, D and Hjerpe, A and El-Andaloussi, S and Hagey, D and Dobra, K}, title = {Diagnostic and Prognostic Utility of the Extracellular Vesicles Subpopulations Present in Pleural Effusion.}, journal = {Biomolecules}, volume = {11}, number = {11}, pages = {}, pmid = {34827604}, issn = {2218-273X}, mesh = {Humans ; *Extracellular Vesicles/metabolism ; Prognosis ; Male ; Female ; *Pleural Effusion/metabolism/diagnosis/pathology ; Aged ; *Biomarkers, Tumor/metabolism ; Middle Aged ; Exosomes/metabolism ; Mesothelioma, Malignant/diagnosis/pathology/metabolism ; Lung Neoplasms/metabolism/diagnosis/pathology ; Mesothelioma/diagnosis/metabolism/pathology ; Pleural Effusion, Malignant/metabolism/diagnosis/pathology ; Aged, 80 and over ; }, abstract = {Extracellular vesicles (EVs), comprising exosomes, microvesicles, and apoptotic bodies, are released by all cells into the extracellular matrix and body fluids, where they play important roles in intercellular communication and matrix remodeling in various pathological conditions. Malignant pleural mesothelioma (MPM) is a primary tumor of mesothelial origin, predominantly related to asbestos exposure. The detection of MPM at an early stage and distinguishing it from benign conditions and metastatic adenocarcinomas (AD) is sometimes challenging. Pleural effusion is often the first available biological material and an ideal source for characterizing diagnostic and prognostic factors. Specific proteins have previously been identified as diagnostic markers in effusion, but it is not currently known whether these are associated with vesicles or released in soluble form. Here, we study and characterize tumor heterogeneity and extracellular vesicle diversity in pleural effusion as diagnostic or prognostic markers for MPM. We analyzed extracellular vesicles and soluble proteins from 27 pleural effusions, which were collected and processed at the department of pathology and cytology at Karolinska University Hospital, representing three different patient groups, MPM (n = 9), benign (n = 6), and AD (n = 12). The vesicles were fractionated into apoptotic bodies, microvesicles, and exosomes by differential centrifugation and characterized by nanoparticle tracking analysis and Western blotting. Multiplex bead-based flow cytometry analysis showed that exosomal markers were expressed differently on EVs present in different fractions. Further characterization of exosomes by a multiplex immunoassay (Luminex) showed that all soluble proteins studied were also present in exosomes, though the ratio of protein concentration present in supernatant versus exosomes varied. The proportion of Angiopoietin-1 present in exosomes was generally higher in benign compared to malignant samples. The corresponding ratios of Mesothelin, Galectin-1, Osteopontin, and VEGF were higher in MPM effusions compared to those in the benign group. These findings demonstrate that relevant diagnostic markers can be recovered from exosomes.}, } @article {pmid34823106, year = {2021}, author = {Nowak, AK and Chin, WL and Keam, S and Cook, A}, title = {Immune checkpoint inhibitor therapy for malignant pleural mesothelioma.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {162}, number = {}, pages = {162-168}, doi = {10.1016/j.lungcan.2021.11.006}, pmid = {34823106}, issn = {1872-8332}, mesh = {Humans ; Immune Checkpoint Inhibitors ; Immunotherapy ; *Lung Neoplasms/drug therapy ; *Mesothelioma/drug therapy ; *Mesothelioma, Malignant ; *Pleural Neoplasms/drug therapy ; }, abstract = {Mesothelioma is a rare and universally fatal cancer linked to exposure to asbestos. Until recently, standard of care treatment was chemotherapy; a treatment resulting in a minimal survival extension, and not improved upon for almost twenty years. However, the advent of cancer immunotherapy - and in particular the immune checkpoint inhibitor class of drugs - has resulted in recently approved new treatment options, with more currently under investigation. Here, we review clinical trials of both single agent and combination checkpoint inhibitors in mesothelioma, plus studies investigating their combination with chemotherapy. We also describe current advances in biomarker identification regarding prediction of patient response to checkpoint inhibitors. Finally, we assess the probable future direction of the field; including where current and developing technologies are likely to lead - in terms of both biomarker discovery and treatment options.}, } @article {pmid34815344, year = {2021}, author = {Novelli, F and Bononi, A and Wang, Q and Bai, F and Patergnani, S and Kricek, F and Haglund, E and Suarez, JS and Tanji, M and Xu, R and Takanishi, Y and Minaai, M and Pastorino, S and Morris, P and Sakamoto, G and Pass, HI and Barbour, H and Gaudino, G and Giorgi, C and Pinton, P and Onuchic, JN and Yang, H and Carbone, M}, title = {BAP1 forms a trimer with HMGB1 and HDAC1 that modulates gene × environment interaction with asbestos.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {118}, number = {48}, pages = {}, pmid = {34815344}, issn = {1091-6490}, support = {R01 CA198138/CA/NCI NIH HHS/United States ; R01 CA237235/CA/NCI NIH HHS/United States ; R01 ES030948/ES/NIEHS NIH HHS/United States ; U01 CA214195/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Asbestos ; Biomarkers, Tumor/metabolism ; Carcinogenesis ; Cell Nucleus/metabolism ; Female ; Gene-Environment Interaction ; Germ-Line Mutation ; HMGB1 Protein/*chemistry/genetics ; Heterozygote ; Histone Deacetylase 1/*chemistry/genetics ; Incidence ; Inflammation ; Male ; Mesothelioma/metabolism ; Mice ; Mutation ; Prognosis ; Protein Binding ; Tumor Suppressor Proteins/*chemistry/metabolism ; Ubiquitin/chemistry ; Ubiquitin Thiolesterase/*chemistry/metabolism ; }, abstract = {Carriers of heterozygous germline BAP1 mutations (BAP1[+/-]) are affected by the "BAP1 cancer syndrome." Although they can develop almost any cancer type, they are unusually susceptible to asbestos carcinogenesis and mesothelioma. Here we investigate why among all carcinogens, BAP1 mutations cooperate with asbestos. Asbestos carcinogenesis and mesothelioma have been linked to a chronic inflammatory process promoted by the extracellular release of the high-mobility group box 1 protein (HMGB1). We report that BAP1[+/-] cells secrete increased amounts of HMGB1, and that BAP1[+/-] carriers have detectable serum levels of acetylated HMGB1 that further increase when they develop mesothelioma. We linked these findings to our discovery that BAP1 forms a trimeric protein complex with HMGB1 and with histone deacetylase 1 (HDAC1) that modulates HMGB1 acetylation and its release. Reduced BAP1 levels caused increased ubiquitylation and degradation of HDAC1, leading to increased acetylation of HMGB1 and its active secretion that in turn promoted mesothelial cell transformation.}, } @article {pmid34788178, year = {2021}, author = {Dodge, DG and Engel, AM and Prueitt, RL and Peterson, MK and Goodman, JE}, title = {US EPA's TSCA risk assessment approach: a case study of asbestos in automotive brakes.}, journal = {Inhalation toxicology}, volume = {33}, number = {9-14}, pages = {295-307}, doi = {10.1080/08958378.2021.1998258}, pmid = {34788178}, issn = {1091-7691}, mesh = {*Asbestos ; Asbestos, Serpentine/analysis ; *Occupational Exposure ; Risk Assessment ; United States ; }, abstract = {The United States Environmental Protection Agency (US EPA) is currently refining its approach for risk assessments conducted under the amended Toxic Substances Control Act (TSCA), largely based on recommendations from the National Academies of Sciences, Engineering, and Medicine (NASEM). We identified several issues with the current TSCA risk assessment approach that were not addressed by NASEM in its recommendations. Here, we demonstrate these issues with a case study of the 'Risk Evaluation for Asbestos, Part 1: Chrysotile Asbestos,' which US EPA released in December 2020. In this evaluation, US EPA found that occupational and some consumer uses of automotive brakes and clutches that contain asbestos result in unreasonable risks. These risks were calculated from estimated exposures during brake work and an inhalation unit risk (IUR) developed for chrysotile asbestos. We found that US EPA overestimated risk as a result of unrealistic inputs to both the exposure and toxicity components of the risk equation, and because the Agency did not fully consider relevant epidemiology and toxicity evidence in its systematic review. Our evaluation demonstrates areas in which the TSCA risk assessment approach could be improved to result in risk evaluations that are supported by the available scientific evidence.}, } @article {pmid34774176, year = {2021}, author = {Sidhu, C and Louw, A and Gary Lee, YC}, title = {Malignant Pleural Mesothelioma: Updates for Respiratory Physicians.}, journal = {Clinics in chest medicine}, volume = {42}, number = {4}, pages = {697-710}, doi = {10.1016/j.ccm.2021.08.006}, pmid = {34774176}, issn = {1557-8216}, mesh = {*Asbestos/adverse effects ; Humans ; *Mesothelioma/diagnosis/therapy ; *Mesothelioma, Malignant ; *Physicians ; *Pleural Neoplasms/diagnosis/therapy ; }, } @article {pmid34768883, year = {2021}, author = {Çakılkaya, P and Sørensen, RR and Jürgensen, HJ and Krigslund, O and Gårdsvoll, H and Nielsen, CF and Santoni-Rugiu, E and Behrendt, N and Engelholm, LH}, title = {The Collagen Receptor uPARAP in Malignant Mesothelioma: A Potential Diagnostic Marker and Therapeutic Target.}, journal = {International journal of molecular sciences}, volume = {22}, number = {21}, pages = {}, pmid = {34768883}, issn = {1422-0067}, support = {No 801481//European Union/ ; NNF19OC0058603//Novo Nordisk Foundation/ ; R231-A13820//Danish Cancer Society/ ; R231-A13832//Danish Cancer Society/ ; N/A//Region Hovedstadens Forskningsfond/ ; N/A//Simon Fougner Hartmanns family foundation/ ; }, mesh = {Adult ; Aged ; Biomarkers, Tumor/genetics ; Cell Line, Tumor ; Female ; Gene Expression ; Humans ; Immunoconjugates/metabolism ; Male ; Mannose-Binding Lectins/*metabolism/physiology ; Membrane Glycoproteins/*metabolism/physiology ; Mesothelioma, Malignant/diagnosis/*metabolism/physiopathology ; Middle Aged ; Receptors, Cell Surface/*metabolism/physiology ; Receptors, Collagen/genetics/metabolism/physiology ; Receptors, Mitogen/genetics ; Transcriptome ; Up-Regulation ; }, abstract = {Malignant mesothelioma (MM) is a highly aggressive cancer with limited therapeutic options. We have previously shown that the endocytic collagen receptor, uPARAP, is upregulated in certain cancers and can be therapeutically targeted. Public RNA expression data display uPARAP overexpression in MM. Thus, to evaluate its potential use in diagnostics and therapy, we quantified uPARAP expression by immunohistochemical H-score in formalin-fixed paraffin-embedded bioptic/surgical human tissue samples and tissue microarrays. We detected pronounced upregulation of uPARAP in the three main MM subtypes compared to non-malignant reactive mesothelial proliferations, with higher expression in sarcomatoid and biphasic than in epithelioid MM. The upregulation appeared to be independent of patients' asbestos exposure and unaffected after chemotherapy. Using immunoblotting, we demonstrated high expression of uPARAP in MM cell lines and no expression in a non-malignant mesothelial cell line. Moreover, we showed the specific internalization of an anti-uPARAP monoclonal antibody by the MM cell lines using flow cytometry-based assays and confocal microscopy. Finally, we demonstrated the sensitivity of these cells towards sub-nanomolar concentrations of an antibody-drug conjugate formed with the uPARAP-directed antibody and a potent cytotoxin that led to efficient, uPARAP-specific eradication of the MM cells. Further studies on patient cohorts and functional preclinical models will fully reveal whether uPARAP could be exploited in diagnostics and therapeutic targeting of MM.}, } @article {pmid34768395, year = {2021}, author = {Zupanc, C and Franko, A and Štrbac, D and Dodič Fikfak, M and Kovač, V and Dolžan, V and Goričar, K}, title = {Serum Calretinin as a Biomarker in Malignant Mesothelioma.}, journal = {Journal of clinical medicine}, volume = {10}, number = {21}, pages = {}, pmid = {34768395}, issn = {2077-0383}, support = {P1-0170, L3-8203, and L3-2622//Slovenian Research Agency/ ; }, abstract = {The early diagnosis of malignant mesothelioma (MM) could improve the prognosis of MM patients. To confirm an MM diagnosis, an immunohistochemical analysis of several tumor tissue markers, including calretinin, is currently required. Our aim is to evaluate serum calretinin as a potential biomarker in asbestos-related diseases, especially in MM. Our study includes 549 subjects: 164 MM patients, 117 subjects with asbestosis, 195 subjects with pleural plaques and 73 occupationally asbestos-exposed subjects without asbestos-related diseases. The serum calretinin concentration was determined with a commercially available enzyme immunoassay. Data on the soluble mesothelin-related peptides (SMRP) concentration are available from previous studies. MM patients had a significantly higher calretinin concentration than subjects without disease, subjects with pleural plaques or subjects with asbestosis (all p < 0.001). The histological type was significantly associated with serum calretinin: patients with sarcomatoid MM had lower calretinin than patients with the epithelioid type (p = 0.001). In a ROC curve analysis, the area under the curve for calretinin concentration predicting MM was 0.826 (95% CI = 0.782-0.869; p < 0.001). At the cutoff value of 0.32 ng/mL, sensitivity was 0.683, while specificity was 0.886. The combination of calretinin and SMRP had the highest predictive value. Calretinin is a useful biomarker that can distinguish MM from other asbestos-related diseases and could, therefore, contribute to an earlier non-invasive diagnosis of MM.}, } @article {pmid34766064, year = {2021}, author = {Ke, H and Gill, AJ and McKenzie, C and Kench, JG and Chan, RCF and Pavlakis, N and Fulham, M and Koh, C and Kao, S}, title = {Malignant Peritoneal Mesothelioma With EWSR1-ATF1 Fusion: A Case Report.}, journal = {JTO clinical and research reports}, volume = {2}, number = {11}, pages = {100236}, pmid = {34766064}, issn = {2666-3643}, abstract = {Malignant mesothelioma with EWSR1-ATF1 fusion is a rare malignancy described in young adults without asbestos exposure. To the best of our knowledge, outcomes to local and systemic therapies for this subtype of malignant mesothelioma have not been described. This case report describes the clinical course of a 19-year-old man diagnosed with malignant peritoneal mesothelioma with EWSR1-ATF1 fusion localized to the abdomen. His disease followed an aggressive course and resulted in limited survival (18 mo). There was treatment resistance to several lines of conventional local and systemic treatments for peritoneal mesothelioma and biologically targeted MET inhibition with crizotinib. More research is required in this rare subtype of peritoneal mesothelioma.}, } @article {pmid34761371, year = {2021}, author = {Rapisarda, V and Broggi, G and Caltabiano, R and Lombardo, C and Castorina, S and Trovato, A and Ledda, C and Filetti, V and Loreto, C}, title = {ATG7 immunohistochemical expression in malignant pleural mesothelioma. A preliminary report.}, journal = {Histology and histopathology}, volume = {36}, number = {12}, pages = {1301-1308}, pmid = {34761371}, issn = {1699-5848}, support = {20722142130//2020/2022 PIA.CE.RI., University of Catania, DIPREME project/ ; }, mesh = {Aged ; Asbestos, Amphibole/*adverse effects ; Autophagy-Related Protein 7/genetics/*metabolism ; Biomarkers, Tumor/metabolism ; Female ; Humans ; *Immunohistochemistry ; Italy/epidemiology ; Lung Neoplasms/*metabolism/pathology ; Male ; Mesothelioma, Malignant/epidemiology/*metabolism ; }, abstract = {Literature evidence has demonstrated a high incidence of asbestos-related malignant pleural mesothelioma (MPM) in a Sicilian town (Biancavilla, Italy), where fluoro-edenite (FE) fibers were discovered some decades ago. As ATG7 immunohistochemical analysis has been ascribed as a prognostic tool of improved survival, we decided to investigate, in MPM patients, exposed and not exposed to FE fibers, the immunohistochemical expression of this autophagy-related protein named ATG7. We analyzed the correlation between ATG7 immunohistochemical level and clinicopathological parameters. Twenty MPM tissue samples, from patients with available clinical and follow-up data, were included in paraffin and processed for immunohistochemistry. The immunohistochemical results confirmed activation of the autophagic process in MPM. Densitometric and morphometric expressions of ATG7 were significantly increased in MPMs when compared to the control tissues. A significant association of a high level of ATG7 with increased survival was demonstrated, with a mean overall survival (OS) of 12.5 months for patients with high expression vs. a mean OS of 4.5 months for patients with low ATG7 expression. In addition, a significant correlation between ATG7 expression and the survival time of MPM patients was observed. This study represents a starting point to hypothesize the prognostic role of ATG7 which could be a reliable prognostic indicator in MPM.}, } @article {pmid34754347, year = {2022}, author = {Touma, T and Taira, R and Makida, T and Oshiro, K and Miyara, T and Taba, Y}, title = {Marked ventilation impairment due to progression of diffuse pleural thickening after cardiac surgery.}, journal = {Radiology case reports}, volume = {17}, number = {1}, pages = {1-4}, pmid = {34754347}, issn = {1930-0433}, abstract = {A 64-year-old Japanese man presented with dyspnea and shortness of breath during exertion. Chest computed tomography revealed bilateral pleural effusion. He was drowsy because of CO2 storage and died due to ventilatory impairment. His past medical history included a thymectomy and adjuvant radiotherapy with thymoma. He had undergone cardiac surgery and permanent pacemaker implantation. The autopsy examination revealed extensive bilateral pleural adhesions and diffuse visceral pleural thickening. An inspection of multiple lung sections failed to detect any asbestos body formation or mesothelioma. The patient's pleural effusion and diffuse pleural thickening may have exacerbated after cardiac surgery. In this case, the progression and pathophysiology of the pleural thickening could be traced by imaging and an autopsy, and we were able to estimate the factors that exacerbated the pleural thickening and ventilation impairment.}, } @article {pmid34749677, year = {2021}, author = {Hemminki, K and Försti, A and Chen, T and Hemminki, A}, title = {Incidence, mortality and survival in malignant pleural mesothelioma before and after asbestos in Denmark, Finland, Norway and Sweden.}, journal = {BMC cancer}, volume = {21}, number = {1}, pages = {1189}, pmid = {34749677}, issn = {1471-2407}, mesh = {Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Asbestos/adverse effects/*standards ; Denmark/epidemiology ; Environmental Exposure/adverse effects/*standards ; Female ; Finland/epidemiology ; History, 20th Century ; History, 21st Century ; Humans ; Incidence ; Male ; Mesothelioma, Malignant/*epidemiology/etiology ; Middle Aged ; Mortality/history/trends ; Norway/epidemiology ; Pleural Neoplasms/*epidemiology/etiology ; Sex Factors ; Survival Analysis ; Sweden/epidemiology ; Young Adult ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare but fatal cancer, which is largely caused by exposure to asbestos. Reliable information about the incidence of MPM prior the influence of asbestos is lacking. The nationwide regional incidence trends for MPM remain poorly characterized. We use nationwide MPM data for Denmark (DK), Finland (FI), Norway (NO) and Sweden (SE) to assess incidence, mortality and survival trends for MPM in these countries.

METHODS: We use the NORDCAN database for the analyses: incidence data were available from 1943 in DK, 1953 in FI and NO and 1958 in SE, through 2016. Survival data were available from 1967 through 2016. World standard population was used in age standardization.

RESULTS: The lowest incidence that we recorded for MPM was 0.02/100,000 for NO women and 0.05/100,000 for FI men in 1953-57, marking the incidence before the influence of asbestos. The highest rate of 1.9/100,000 was recorded for DK in 1997. Female incidence was much lower than male incidence. In each country, the male incidence trend for MPM culminated, first in SE around 1990. The regional incidence trends matched with earlier asbestos-related industrial activity, shipbuilding in FI and SE, cement manufacturing and shipbuilding in DK and seafaring in NO. Relative 1-year survival increased from about 20 to 50% but 5-year survival remained at or below 10%.

CONCLUSION: In the Nordic countries, the male incidence trends for MPM climaxed and started to decrease, indicating that the prevention of exposure was beneficial. Survival in MPM has improved for both sexes but long-term survival remains dismal.}, } @article {pmid34740982, year = {2022}, author = {Hessel, PA}, title = {Mesothelioma among vehicle mechanics: a controversy?.}, journal = {Thorax}, volume = {77}, number = {5}, pages = {426-427}, doi = {10.1136/thoraxjnl-2021-217880}, pmid = {34740982}, issn = {1468-3296}, mesh = {*Asbestos ; Humans ; *Lung Neoplasms/epidemiology/etiology ; *Mesothelioma/etiology ; *Mesothelioma, Malignant ; *Occupational Diseases ; *Occupational Exposure ; }, } @article {pmid34738103, year = {2022}, author = {Inamasu, E and Tsuchiya, T and Yamauchi, M and Nishi, K and Matsuda, K and Sugawara, F and Sakaguchi, K and Mori, R and Matsumoto, K and Miyazaki, T and Hatachi, G and Doi, R and Watanabe, H and Tomoshige, K and Matsuda, N and Higami, Y and Shimokawa, I and Nakashima, M and Nagayasu, T}, title = {Anticancer agent α-sulfoquinovosyl-acylpropanediol enhances the radiosensitivity of human malignant mesothelioma in nude mouse models.}, journal = {Journal of radiation research}, volume = {63}, number = {1}, pages = {19-29}, pmid = {34738103}, issn = {1349-9157}, support = {//Nagasaki University/ ; }, mesh = {Animals ; *Antineoplastic Agents/therapeutic use ; Cell Line, Tumor ; Humans ; Male ; *Mesothelioma/drug therapy/metabolism/radiotherapy ; *Mesothelioma, Malignant ; Mice ; Mice, Nude ; *Pleural Neoplasms/drug therapy/metabolism/radiotherapy ; Radiation Tolerance ; }, abstract = {Malignant pleural mesothelioma (MPM) is a highly malignant disease that develops after asbestos exposure. Although the number of MPM cases is predicted to increase, no effective standard therapies have been established. The novel radiosensitizer α-sulfoquinovosyl-acylpropanediol (SQAP) enhances the effects of γ-radiation in human lung and prostate cancer cell lines and in animal models. In this study, we explored the radiosensitizing effect of SQAP and its mechanisms in MPM. The human MPM cell lines MSTO-211H and MESO-4 were implanted subcutaneously into the backs and thoracic cavities of immunodeficient KSN/Slc mice, then 2 mg/kg SQAP was intravenously administered with or without irradiation with a total body dose of 8 Gy. In both the orthotopic and ectopic xenograft murine models, the combination of irradiation plus SQAP delayed the implanted human MSTO-211H tumor growth. The analysis of the changes in the relative tumor volume of the MSTO-211H indicated a statistically significant difference after 8 Gy total body combined with 2 mg/kg SQAP, compared to both the untreated control (P = 0.0127) and the radiation treatment alone (P = 0.0171). After the treatment in each case, immunostaining of the harvested tumors revealed decreased cell proliferation, increased apoptosis and normalization of tumor blood vessels in the SQAP- and irradiation-treated group. Furthermore, hypoxia-inducible factor (HIF) 1 mRNA and protein expression were decreased, indicating reoxygenation in this group. In conclusion, SQAP improved hypoxic conditions in tumor tissue and may elicit a radiosensitizing effect in malignant mesothelioma models.}, } @article {pmid34725624, year = {2021}, author = {Gupta, A and Vasileva, A and Manthri, S}, title = {The Rarest of the Rare: A Case of BAP1-Mutated Primary Peritoneal Mesothelioma.}, journal = {Cureus}, volume = {13}, number = {9}, pages = {e18380}, pmid = {34725624}, issn = {2168-8184}, abstract = {Malignant mesotheliomas (MM), as described are rare tumors that are mostly associated with occupational exposure to asbestos. They most commonly occur in the pleura. Other unfamiliar sites where they can occur are the peritoneum, pericardium, and tunica vaginalis. There is no significant correlation between the amount and duration of asbestos exposure to mesothelioma development as reported by various studies over the years. Apart from the environmental exposure, the development of malignant mesothelioma has been linked to a mutation in the BAP1 gene, which can predispose the patient to develop other malignancies associated with BAP1 mutation. We report a case of a 43-year-old man without any significant risk factors, who presented with a complaint of abdominal discomfort and was found to have malignant peritoneal mesothelioma (MPM). With a known familial history of mesothelioma and melanoma, our patient underwent genetic testing which revealed a mutation in BAP1, affirming the strong association with the development of MPM. Young patients who develop malignant mesothelioma without risk factors for MM should have germline testing for BAP1. This case report is unique and highlights a familial variant of mesothelioma, even rare with peritoneal mesothelioma in our patient.}, } @article {pmid34698447, year = {2022}, author = {Danese, MD and Daumont, M and Nwokeji, E and Gleeson, M and Penrod, JR and Lubeck, D}, title = {Treatment patterns and outcomes in older patients with advanced malignant pleural mesothelioma: Analyses of Surveillance, Epidemiology, and End Results-Medicare data.}, journal = {Cancer reports (Hoboken, N.J.)}, volume = {5}, number = {9}, pages = {e1568}, pmid = {34698447}, issn = {2573-8348}, mesh = {Aged ; Female ; Humans ; Male ; Medicare ; *Mesothelioma/drug therapy/epidemiology ; *Mesothelioma, Malignant ; Pemetrexed/therapeutic use ; Platinum/therapeutic use ; *Pleural Neoplasms/drug therapy/epidemiology ; Retrospective Studies ; United States/epidemiology ; }, abstract = {BACKGROUND: Malignant mesothelioma is a rare neoplasm associated with asbestos exposure. Characterizing treatment patterns and outcomes of older patients with advanced malignant pleural mesothelioma (MPM) is important to understand the unmet needs of this population.

AIM: To evaluate the demographic and clinical characteristics, treatment patterns, and outcomes among older patients diagnosed with advanced MPM in the United States between 2007 and 2013.

METHODS: This was a retrospective cohort study using Surveillance, Epidemiology, and End Results (SEER) data linked with Medicare claims. We included patients who were age 66 or older at the time of their primary MPM diagnosis between 2007 and 2013 and followed them through 2014. Treated patients who received first-line chemotherapy with pemetrexed and platinum within 90 days of diagnosis, second-line, or third-line therapy were identified for evaluation of outcomes.

RESULTS: There were 666 older patients with advanced MPM, of whom 82% were male, 87% White, 78% stage IV, and 70% had no mobility limitation indicators at diagnosis. There were 262 patients who received first-line chemotherapy for advanced MPM, most of whom (80%; n = 209) received pemetrexed-platinum. Of these 209 patients, 41% (n = 86) initiated second-line therapy, and 26% (n = 22) initiated third-line therapy. Median overall survival for the cohort of 209 patients was 7.2 months. Patients with epithelioid histology had better median overall survival (12.2 months) compared with other histologies (4.4-5.6 months). Within 90 days of diagnosis of advanced MPM, 78% of patients were hospitalized, 52% visited an emergency department, and 21% had hospice care. The 2-year cost of care was over $100 000 for all patients with advanced MPM treated with first-line pemetrexed-platinum.

CONCLUSIONS: Although first-line systemic anticancer treatment was generally consistent with guidelines (e.g., pemetrexed-platinum), poor patient outcomes highlight the need for effective treatment options for older patients with advanced MPM.}, } @article {pmid34689163, year = {2021}, author = {Shrestha, S and Adhikary, G and Naselsky, W and Xu, W and Friedberg, JS and Eckert, RL}, title = {ACTL6A suppresses p21[Cip1] tumor suppressor expression to maintain an aggressive mesothelioma cancer cell phenotype.}, journal = {Oncogenesis}, volume = {10}, number = {10}, pages = {70}, pmid = {34689163}, issn = {2157-9024}, support = {R01 CA211909/CA/NCI NIH HHS/United States ; T32 CA154274/CA/NCI NIH HHS/United States ; R01 CA211909/CA/NCI NIH HHS/United States ; }, abstract = {Mesothelioma is a poor prognosis cancer of the mesothelial lining that develops in response to exposure to various agents including asbestos. Actin-Like Protein 6A (ACTL6A, BAF53a) is a SWI/SNF regulatory complex protein that is elevated in cancer cells and has been implicated as a driver of cancer cell survival and tumor formation. In the present study, we show that ACTL6A drives mesothelioma cancer cell proliferation, spheroid formation, invasion, and migration, and that these activities are markedly attenuated by ACTL6A knockdown. ACTL6A expression reduces the levels of the p21[Cip1] cyclin-dependent kinase inhibitor and tumor suppressor protein. DNA binding studies show that ACTL6A interacts with Sp1 and p53 binding DNA response elements in the p21[Cip1] gene promoter and that this is associated with reduced p21[Cip1] promoter activity and p21[Cip1] mRNA and protein levels. Moreover, ACTL6A suppression of p21[Cip1] expression is required for maintenance of the aggressive mesothelioma cancer cell phenotype suggesting that p21[Cip1] is a mediator of ACTL6A action. p53, a known inducer of p21[Cip1] expression, is involved ACTL6A in regulation of p21[Cip1] in some but not all mesothelioma cells. In addition, ACTL6A knockout markedly reduces tumor formation and this is associated with elevated tumor levels of p21[Cip1]. These findings suggest that ACTL6A suppresses p21[Cip1] promoter activity to reduce p21[Cip1] protein as a mechanism to maintain the aggressive mesothelioma cell phenotype.}, } @article {pmid34682428, year = {2021}, author = {Kim, EA}, title = {Standardized Incidence Ratio and Standardized Mortality Ratio of Malignant Mesothelioma in a Worker Cohort Using Employment Insurance Database in Korea.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {20}, pages = {}, pmid = {34682428}, issn = {1660-4601}, mesh = {Employment ; Female ; Humans ; Incidence ; *Insurance ; Male ; *Mesothelioma, Malignant ; *Occupational Exposure ; Republic of Korea/epidemiology ; }, abstract = {Malignant mesothelioma is one of the appropriate indicators for assessing the carcinogenic effects of asbestos. This study compared the risk ratio of mesothelioma according to the industry in the worker cohort. A cohort was constructed using the Korean employment insurance system during 1995-2017, enrolling 13,285,895 men and 10,452,705 women. The standardized mortality ratio (SMR) and standardized incidence ratio (SIR) were calculated using the indirect standardization method. There were 641 malignant mesotheliomas that occurred; the SIR was significantly higher than the general population (men 1.36, 95% confidence interval (CI) 1.24-1.48, women 1.44, 95% CI: 1.23-1.7). More than half (52.8%) of malignant mesothelioma cases occurred in the manufacturing (n = 240, 38.6%, SIR: men, 1.72, 95% CI: 1.37-2.15, women, 3.31, 95% CI: 1.71-5.79) and construction industries (n = 88, 14.2%, SIR: men, 1.54 95% CI: 1.33-1.78, women, 1.62 95% CI: 1.25-2.11). The accommodation and food service (men, 2.56 95% CI: 1.28-4.58, women 1.35, 95% CI: 0.65-2.48) and real estate (men 1.34, 95% CI: 0.98-1.83, women 1.95, 95% CI: 0.78-4.02) also showed a high SIR, indicating the risk of asbestos-containing materials in old buildings. The incidence of malignant mesothelioma is likely to increase in the future, given the long latency of this disease. Moreover, long-term follow-up studies will be needed.}, } @article {pmid34681644, year = {2021}, author = {Badger, R and Park, K and Pietrofesa, RA and Christofidou-Solomidou, M and Serve, KM}, title = {Late Inflammation Induced by Asbestiform Fibers in Mice Is Ameliorated by a Small Molecule Synthetic Lignan.}, journal = {International journal of molecular sciences}, volume = {22}, number = {20}, pages = {}, pmid = {34681644}, issn = {1422-0067}, mesh = {Adaptive Immunity/drug effects ; Animals ; Asbestos, Amphibole/*toxicity ; B-Lymphocytes/cytology/immunology/metabolism ; Butylene Glycols/pharmacology/*therapeutic use ; Chemokine CCL2/metabolism ; Female ; Glucosides/pharmacology/*therapeutic use ; Immunity, Innate/drug effects ; Immunoglobulin Isotypes/metabolism ; Immunoglobulins/metabolism ; Inflammation/chemically induced/pathology/*prevention & control ; Interleukin-6 ; Male ; Mice ; Mice, Inbred C57BL ; Oxidative Stress/drug effects/genetics ; T-Lymphocytes/cytology/immunology/metabolism ; }, abstract = {Exposure to Libby amphibole (LA) asbestos-like fibers is associated with increased risk of asbestosis, mesothelioma, pulmonary disease, and systemic autoimmune disease. LGM2605 is a small molecule antioxidant and free radical scavenger, with anti-inflammatory effects in various disease models. The current study aimed to determine whether the protective effects of LGM2605 persist during the late inflammatory phase post-LA exposure. Male and female C57BL/6 mice were administered daily LGM2605 (100 mg/kg) via gel cups for 3 days before and 14 days after a 200 µg LA given via intraperitoneal (i.p.) injection. Control mice were given unsupplemented gel cups and an equivalent dose of i.p. saline. On day 14 post-LA treatment, peritoneal lavage was assessed for immune cell influx, cytokine concentrations, oxidative stress biomarkers, and immunoglobulins. During the late inflammatory phase post-LA exposure, we noted an alteration in trafficking of both innate and adaptive immune cells, increased pro-inflammatory cytokine concentrations, induction of immunoglobulin isotype switching, and increased oxidized guanine species. LGM2605 countered these changes similarly among male and female mice, ameliorating late inflammation and altering immune responses in late post-LA exposure. These data support possible efficacy of LGM2605 in the prolonged treatment of LA-associated disease and other inflammatory conditions.}, } @article {pmid34679210, year = {2021}, author = {Hiraku, Y and Watanabe, J and Kaneko, A and Ichinose, T and Murata, M}, title = {MicroRNA expression in lung tissues of asbestos-exposed mice: Upregulation of miR-21 and downregulation of tumor suppressor genes Pdcd4 and Reck.}, journal = {Journal of occupational health}, volume = {63}, number = {1}, pages = {e12282}, pmid = {34679210}, issn = {1348-9585}, support = {23659328//Ministry of Education, Culture, Sports, Science and Technology, Japan/ ; 24390153//Ministry of Education, Culture, Sports, Science and Technology, Japan/ ; 15H04784//Ministry of Education, Culture, Sports, Science and Technology, Japan/ ; 18H03038//Ministry of Education, Culture, Sports, Science and Technology, Japan/ ; //Grants-in-Aid for Scientific Research/ ; }, mesh = {Animals ; Apoptosis Regulatory Proteins/*genetics ; Asbestos/toxicity ; Asbestos, Crocidolite/*administration & dosage ; Asbestos, Serpentine/*administration & dosage ; Disease Models, Animal ; Down-Regulation ; GPI-Linked Proteins/*genetics ; Gene Expression/*drug effects ; Lung/pathology ; Male ; Mice ; Mice, Inbred ICR ; MicroRNAs/*genetics ; Microarray Analysis ; RNA-Binding Proteins/*genetics ; Up-Regulation ; }, abstract = {OBJECTIVES: Asbestos causes lung cancer and malignant mesothelioma in humans, but the precise mechanism has not been well understood. MicroRNA (miRNA) is a short non-coding RNA that suppresses gene expression and participates in human diseases including cancer. In this study, we examined the expression levels of miRNA and potential target genes in lung tissues of asbestos-exposed mice by microarray analysis.

METHODS: We intratracheally administered asbestos (chrysotile and crocidolite, 0.05 or 0.2 mg/instillation) to 6-week-old ICR male mice four times weekly. We extracted total RNA from lung tissues and performed microarray analysis for miRNA and gene expression. We also carried out real-time polymerase chain reaction (PCR), Western blotting, and immunohistochemistry to confirm the results of microarray analysis.

RESULTS: Microarray analysis revealed that the expression levels of 14 miRNAs were significantly changed by chrysotile and/or crocidolite (>2-fold, P < .05). Especially, miR-21, an oncogenic miRNA, was significantly upregulated by both chrysotile and crocidolite. In database analysis, miR-21 was predicted to target tumor suppressor genes programmed cell death 4 (Pdcd4) and reversion-inducing-cysteine-rich protein with kazal motifs (Reck). Although real-time PCR showed that Pdcd4 was not significantly downregulated by asbestos exposure, Western blotting and immunohistochemistry revealed that PDCD4 expression was reduced especially by chrysotile. Reck was significantly downregulated by chrysotile in real-time PCR and immunohistochemistry.

CONCLUSIONS: This is the first study demonstrating that miR-21 was upregulated and corresponding tumor suppressor genes were downregulated in lung tissues of asbestos-exposed animals. These molecular events are considered to be an early response to asbestos exposure and may contribute to pulmonary toxicity and carcinogenesis.}, } @article {pmid34676483, year = {2022}, author = {Sonobe, M and Kou, Y and Yamazaki, N and Sakaguchi, Y and Tanaka, H}, title = {Staged removal of artificial patches for thoracic empyema after extrapleural pneumonectomy for diffuse malignant pleural mesothelioma.}, journal = {General thoracic and cardiovascular surgery}, volume = {70}, number = {2}, pages = {193-196}, pmid = {34676483}, issn = {1863-6713}, mesh = {Aged ; *Empyema, Pleural/etiology/surgery ; Humans ; Male ; *Mesothelioma/surgery ; *Mesothelioma, Malignant ; *Pleural Neoplasms/surgery ; Pneumonectomy/adverse effects ; }, abstract = {A 69-year-old man with occupational exposure to asbestos was referred to our hospital with right diffuse malignant pleural mesothelioma. He underwent extrapleural pneumonectomy with reconstruction of the pericardium and diaphragm using elongated polytetrafluoroethylene patches, followed by postoperative chemotherapy and chest wall irradiation. One year later, he was hospitalized because of a right empyema caused by Escherichia coli infection. As chest drainage and systemic antibiotics did not eliminate the abscess around the artificial patches, a Clagett window was created. To avoid mediastinal and liver overshift into the right thoracic cavity, we only performed partial resection of the diaphragm patch and incision of the artificial pericardium. After 19 days of irrigation and dressing change, the artificial patches were completely removed. Two months later, the patient provided a culture-negative sample and had an improved nutritional status; we therefore performed closure of the Clagett window with thoracoplasty. He did not experience recurrence of empyema.}, } @article {pmid34673618, year = {2021}, author = {Sunitha, S and Shah, AH and Gami, A and Trivedi, P}, title = {Thigh mass in a patient with malignant pleural mesothelioma: Metastasis at an unusual site.}, journal = {Indian journal of pathology & microbiology}, volume = {64}, number = {4}, pages = {834-836}, doi = {10.4103/IJPM.IJPM_463_20}, pmid = {34673618}, issn = {0974-5130}, mesh = {Asbestos/adverse effects ; Humans ; Male ; Medicine, Ayurvedic ; Mesothelioma, Malignant/*pathology ; Middle Aged ; Muscle Neoplasms/*secondary ; Occupational Exposure/adverse effects ; Pleural Cavity/pathology ; Soft Tissue Neoplasms/*pathology ; Thigh/*pathology ; }, abstract = {Soft tissue tumors are a highly heterogeneous group of lesions with varied clinical presentation. The majority is primary tumors and metastatic tumors are very rare. Malignant pleural mesothelioma presenting as a soft tissue mass at a distant site is even rarer and can cause diagnostic challenges both clinically and pathologically. We report a case of malignant pleural mesothelioma presenting as a soft tissue mass in the left thigh. A 59-year-old man, non-smoker, working in a cement factory since 30 years presented with complains of difficulty in walking since 1½ months. Review of his previous medical records revealed malignant pleural mesothelioma, which was diagnosed 9 months before. He had denied chemotherapy and was on Ayurvedic medication. The lesion involved the adjacent intercostal muscles. Few enlarged lymph nodes were noted in mediastinal and cervical regions. Biopsy of left supraclavicular and right cervical lymph nodes showed metastases. Metastasis from malignant pleural mesothelioma to the thigh was confirmed by immunohistochemistry. The tumor was positive for CK5/6, CK7, Calretinin and vimentin and immunonegative for CEA, Napsin A and TTF 1.}, } @article {pmid34664557, year = {2021}, author = {Sánchez-Trujillo, L and Sanz-Anquela, JM and Ortega, MA}, title = {Use of the Minimum Basic Data Set as a tool for the epidemiological surveillance of mesothelioma.}, journal = {Anales del sistema sanitario de Navarra}, volume = {44}, number = {3}, pages = {405-415}, doi = {10.23938/ASSN.0969}, pmid = {34664557}, issn = {2340-3527}, mesh = {*Asbestos/adverse effects ; Humans ; Incidence ; *Mesothelioma/epidemiology ; *Mesothelioma, Malignant ; Spain/epidemiology ; }, abstract = {BACKGROUND: Mesothelioma is a very aggressive tumor that appears after several decades of asbestos exposure. The Minimum Basic Data Set (MBDS) has been validated for the incidence of mesothelioma in Italy, but not in Spain. The objectives of this investigation are: to estimate the prevalence, incidence and mortality of mesothelioma in the Community of Madrid (CM); to evaluate the distribution of this risk within the territory; and to explore validity of the MBDS in the epidemiological surveillance of mesothelioma.

METHODS: Prevalence, incidence and mortality mesothelioma rates were calculated for the CM from data of the MBDS (2016 and 2017), and mortality data of the Spanish National Statistics Institute (INE) for the same period. The geographical distribution of cases and deaths, and its correlation at municipal level was studied. Statistical analysis with R and Excel tools was carried out.

RESULTS: The incidence of mesothelioma in the CM was higher than in previous years. Mortality estimated by the MBDS and calculated using INE data for 2016 were similar in the CM. The correlation between the geographical patterns of risk of mesothelioma obtained from the two sources was high (r = 0.86). The aggregation of cases continues in municipalities in the south, detecting the maximum risk in Aranjuez.

CONCLUSION: The MBDS and INE are good resources for monitoring the risk of mesothelioma. New studies that investigate the aggregation of cases in Aranjuez are required.}, } @article {pmid34663305, year = {2021}, author = {Sato, T and Nakanishi, H and Akao, K and Okuda, M and Mukai, S and Kiyono, T and Sekido, Y}, title = {Three newly established immortalized mesothelial cell lines exhibit morphological phenotypes corresponding to malignant mesothelioma epithelioid, intermediate, and sarcomatoid types, respectively.}, journal = {Cancer cell international}, volume = {21}, number = {1}, pages = {546}, pmid = {34663305}, issn = {1475-2867}, support = {JP19H03527//japan society for the promotion of science/ ; JP18K07255//japan society for the promotion of science/ ; 20K16462//japan society for the promotion of science/ ; }, abstract = {BACKGROUND: Malignant mesothelioma (MM) is a very aggressive tumor that develops from mesothelial cells, mainly due to asbestos exposure. MM is categorized into three major histological subtypes: epithelioid, sarcomatoid, and biphasic, with the biphasic subtype containing both epithelioid and sarcomatoid components. Patients with sarcomatoid mesothelioma usually show a poorer prognosis than those with epithelioid mesothelioma, but it is not clear how these morphological phenotypes are determined or changed during the oncogenic transformation of mesothelial cells.

METHODS: We introduced the E6 and E7 genes of human papillomavirus type 16 and human telomerase reverse transcriptase gene in human peritoneal mesothelial cells and established three morphologically different types of immortalized mesothelial cell lines.

RESULTS: HOMC-B1 cells exhibited epithelioid morphology, HOMC-A4 cells were fibroblast-like, spindle-shaped, and HOMC-D4 cells had an intermediate morphology, indicating that these three cell lines closely mimicked the histological subtypes of MM. Gene expression profiling revealed increased expression of NOD-like receptor signaling-related genes in HOMC-A4 cells. Notably, the combination treatment of HOMC-D4 cells with TGF-β and IL-1β induced a morphological change from intermediate to sarcomatoid morphology.

CONCLUSIONS: Our established cell lines are useful for elucidating the fundamental mechanisms of mesothelial cell transformation and mesothelial-to-mesenchymal transition.}, } @article {pmid34656224, year = {2021}, author = {Nowak, AK}, title = {CONFIRMing single-drug immune checkpoint blockade efficacy in mesothelioma.}, journal = {The Lancet. Oncology}, volume = {22}, number = {11}, pages = {1485-1487}, doi = {10.1016/S1470-2045(21)00516-7}, pmid = {34656224}, issn = {1474-5488}, mesh = {Clinical Trials as Topic ; Humans ; Immune Checkpoint Inhibitors/*therapeutic use ; Immunotherapy/*methods ; Mesothelioma/*drug therapy/immunology/pathology ; Pharmaceutical Preparations/*administration & dosage ; }, } @article {pmid34652478, year = {2022}, author = {Ebbinghaus-Mier, D and Ebbinghaus, R and Prager, HM and Schöps, W and Golka, K}, title = {[Mesothelioma of the tunica vaginalis of the testis-a histopathological finding with far-reaching consequences].}, journal = {Der Urologe. Ausg. A}, volume = {61}, number = {3}, pages = {292-296}, pmid = {34652478}, issn = {1433-0563}, mesh = {Humans ; Male ; *Mesothelioma/diagnosis/etiology/surgery ; *Mesothelioma, Malignant ; *Testicular Hydrocele/diagnosis/etiology/surgery ; *Testicular Neoplasms/diagnosis/pathology/surgery ; }, abstract = {Mesotheliomas are very aggressive tumors, almost exclusively caused by asbestos. Four of the 5 mesotheliomas assessed in the years 2014-2020 were recognized as occupational diseases, the 5th case was discontinued due to lack of the patient's cooperation. Surgical exposure of the testis was performed under the suspected diagnoses of hydrocele (n = 3), spermatocele (n = 1) as well as "unknown" (n = 1). This proves that a histopathological examination of removed tissue is the gold standard in scrotal interventions. Every mesothelioma must always be reported as an occupational disease.}, } @article {pmid34651555, year = {2021}, author = {Paustenbach, D and Brew, D and Ligas, S and Heywood, J}, title = {A critical review of the 2020 EPA risk assessment for chrysotile and its many shortcomings.}, journal = {Critical reviews in toxicology}, volume = {51}, number = {6}, pages = {509-539}, doi = {10.1080/10408444.2021.1968337}, pmid = {34651555}, issn = {1547-6898}, mesh = {Aged ; *Asbestos ; Asbestos, Serpentine/toxicity ; Humans ; *Lung Neoplasms ; *Mesothelioma ; *Occupational Exposure ; Risk Assessment ; Tumor Suppressor Proteins ; Ubiquitin Thiolesterase ; United States/epidemiology ; United States Environmental Protection Agency ; }, abstract = {From 2018 to 2020, the United States Environmental Protection Agency (EPA) performed a risk evaluation of chrysotile asbestos to evaluate the hazards of asbestos-containing products (e.g. encapsulated products), including brakes and gaskets, allegedly currently sold in the United States. During the public review period, the EPA received more than 100 letters commenting on the proposed risk evaluation. The Science Advisory Committee on Chemicals (SACC), which peer reviewed the document, asked approximately 100 questions of the EPA that they expected to be addressed prior to publication of the final version of the risk assessment on 30 December 2020. After careful analysis, the authors of this manuscript found many significant scientific shortcomings in both the EPA's draft and final versions of the chrysotile risk evaluation. First, the EPA provided insufficient evidence regarding the current number of chrysotile-containing brakes and gaskets being sold in the United States, which influences the need for regulatory oversight. Second, the Agency did not give adequate consideration to the more than 200 air samples detailed in the published literature of auto mechanics who changed brakes in the 1970-1989 era. Third, the Agency did not consider more than 15 epidemiology studies indicating that exposures to encapsulated chrysotile asbestos in brakes and gaskets, which were generally in commerce from approximately 1950-1985, did not increase the incidence of any asbestos-related disease. Fourth, the concern about chrysotile asbestos being a mesothelioma hazard was based on populations in two facilities where mixed exposure to chrysotile and commercial amphibole asbestos (amosite and crocidolite) occurred. All 8 cases of pleural cancer and mesothelioma in the examined populations arose in facilities where amphiboles were present. It was therefore inappropriate to rely on these cohorts to predict the health risks of exposure to short fiber chrysotile, especially of those fibers filled with phenolic resins. Fifth, the suggested inhalation unit risk (IUR) for chrysotile asbestos was far too high since it was not markedly different than for amosite, despite the fact that the amphiboles are a far more potent carcinogen. Sixth, the approach to low dose modeling was not the most appropriate one in several respects, but, without question, it should have accounted for the background rate of mesothelioma in the general population. Just one month after this assessment was published, the National Academies of Science notified the EPA that the Agency's systematic review process was flawed. The result of the EPA's chrysotile asbestos risk evaluation is that society can expect dozens of years of scientifically unwarranted litigation. Due to an aging population and because some fraction of the population is naturally predisposed to mesothelioma given the presence of various genetic mutations in DNA repair mechanisms (e.g. BAP1 and others), the vast majority of mesotheliomas in the post-2035 era are expected to be spontaneous and unrelated in any way to exposure to asbestos. Due to the EPA's analysis, it is our belief that those who handled brakes and gaskets in the post-1985 era may now believe that those exposures were the cause of their mesothelioma, when a risk assessment based on the scientific weight of evidence would indicate otherwise.}, } @article {pmid34649858, year = {2021}, author = {Magnavita, N and Congedo, MT and Di Prinzio, RR and Iuliano, A}, title = {War journalism: an occupational exposure.}, journal = {BMJ case reports}, volume = {14}, number = {10}, pages = {}, pmid = {34649858}, issn = {1757-790X}, mesh = {*Asbestos/toxicity ; Dust ; Humans ; Male ; *Mesothelioma/chemically induced ; Middle Aged ; *Occupational Diseases/etiology ; *Occupational Exposure/adverse effects ; *Pleural Neoplasms ; Silicon Dioxide ; }, abstract = {Apart from the risk of accidents, war theatres present a hazard related to numerous long-lasting toxic agents. For 10 years, a >60-year-old male journalist worked in war theatres in the Far and Near East where he was exposed to asbestos and other toxic substances (metals, silica, clays, polycyclic aromatic hydrocarbons and other organic substances) contained in dust and smoke of destroyed buildings. More than 15 years later, he developed a mucoepidermoid carcinoma of the soft palate and, subsequently, a pleural malignant mesothelioma. The safety of war journalists should focus not only on preventing the risk of being killed, but also on providing protection from toxic and carcinogenic agents. Exposure to substances released during the destruction of buildings can also pose a carcinogenic risk for survivors.}, } @article {pmid34645127, year = {2021}, author = {Angelini, A and Chellini, E}, title = {[Inventory of occupational exposure to asbestos with particular reference to Tuscan workers].}, journal = {Epidemiologia e prevenzione}, volume = {45}, number = {5 Suppl 1}, pages = {1-120}, doi = {10.19191/EP21.5S1.073}, pmid = {34645127}, issn = {1120-9763}, mesh = {*Asbestos/toxicity ; Carcinogens/toxicity ; Humans ; Italy/epidemiology ; *Mesothelioma/chemically induced/epidemiology ; *Occupational Diseases/epidemiology ; *Occupational Exposure/adverse effects ; *Pleural Neoplasms/epidemiology/etiology ; }, abstract = {This Catalogue is a collection of information on the use of raw asbestos and asbestos-containing materials used in several industries and occupational activities, with particular attention to the situation of Tuscany, a region of Central Italy. The work was developed at the Institute for Cancer Research, Prevention and Clinical Network (ISPRO) of Florence, where epidemiologic research and surveillance activities have been developing since 1988 and where the coordination and evaluation of the regional health surveillance programme provided to past asbestos workers started in 2016 and is still ongoing. The Catalogue aims at being a working tool for all health professionals engaged in examining and classifying the occupational asbestos exposures of subjects both affected by diseases that could be associated to this carcinogen and examined within the regional health surveillance programme. It is necessary for the health personnel engaged in the above-mentioned activities to know or to have the possibility to find exact and detailed data on asbestos exposure by occupational sector. These data are briefly described in the 29 factsheets this Catalogue consists of. In each factsheet, the presence and every use of asbestos are described, with reference to a precise occupational sector. Several occupational sectors can be considered together because of analogies on asbestos exposure. Occupations are considered on the basis of existing evidence on the use of raw asbestos or asbestos-containing materials (as semi-finished or finished products or as auxiliary materials in production processes). Besides the presence and use of asbestos, a description of the possible exposures of workers is reported. Sources of information were scientific and grey literature as well as the 7,187 occupational histories of mesothelioma registered by the specific Tuscan registry. Some factsheets have been revised and enhanced by Italian experts on the asbestos exposure with a specific competence in the examined sectors. Each factsheet includes also questions to be addressed to workers in order to examine in depth their possible asbestos exposure. For those who would like to expand their knowledge on this topic, references are reported both at the end of each factsheet and at the end of the volume. In all industrialized countries, also in those which have not already banned asbestos use, a decrease in the use of this material and in the relative exposure have been observing since the end of the Seventies, few years after the general consensus within the scientific community on asbestos carcinogenicity. This decreasing trend has been becoming greater and greater since the end of the Eighties, when more restrictive regulations have been approved and applied, especially in occupational settings. Nevertheless, nowadays asbestos-related diseases are still diagnosed due to past exposures, although during next decade a decreasing incidence of malignant mesothelioma - the cancer most specifically related to this carcinogen and characterized by a very bad prognosis and the longest latency - could be observed. Particular attention will be paid to jobs regarding renovation of old buildings containing asbestos and to decontamination activities. In conclusion, this Catalogue is a working tool - although it is not exhaustive and could be upgraded with new information - for all professionals engaged in asbestos risk prevention activities as health personnel, personnel of insurance companies, employers, and employee representatives.}, } @article {pmid34641979, year = {2021}, author = {Kuroda, A}, title = {Recent progress and perspectives on the mechanisms underlying Asbestos toxicity.}, journal = {Genes and environment : the official journal of the Japanese Environmental Mutagen Society}, volume = {43}, number = {1}, pages = {46}, pmid = {34641979}, issn = {1880-7046}, support = {JPMEERF201950001//environmental restoration and conservation agency/ ; 19H04291//japan society for the promotion of science/ ; }, abstract = {Most cases of mesothelioma are known to result from exposure to asbestos fibers in the environment or occupational ambient air. The following questions regarding asbestos toxicity remain partially unanswered: (i) why asbestos entering the alveoli during respiration exerts toxicity in the pleura; and (ii) how asbestos causes mesothelioma, even though human mesothelial cells are easily killed upon exposure to asbestos. As for the latter question, it is now thought that the frustrated phagocytosis of asbestos fibers by macrophages prolongs inflammatory responses and gives rise to a "mutagenic microenvironment" around mesothelial cells, resulting in their malignant transformation. Based on epidemiological and genetic studies, a carcinogenic model has been proposed in which BRCA1-associated protein 1 mutations are able to suppress cell death in mesothelial cells and increase genomic instability in the mutagenic microenvironment. This leads to additional mutations, such as CDKN2A [p16], NF2, TP53, LATS2, and SETD2, which are associated with mesothelioma carcinogenesis. Regarding the former question, the receptors involved in the intracellular uptake of asbestos and the mechanism of transfer of inhaled asbestos from the alveoli to the pleura are yet to be elucidated. Further studies using live-cell imaging techniques will be critical to fully understanding the mechanisms underlying asbestos toxicity.}, } @article {pmid34641792, year = {2021}, author = {Kelarji, AB and Alshutaihi, MS and Ghazal, A and Mahli, N and Agha, S}, title = {A rare case of benign multicystic peritoneal mesothelioma misdiagnosed as hydatid cyst found in the liver parenchyma and abdomen cavity of a male with asbestos exposure.}, journal = {BMC gastroenterology}, volume = {21}, number = {1}, pages = {374}, pmid = {34641792}, issn = {1471-230X}, mesh = {Abdomen ; *Asbestos ; Diagnostic Errors ; *Echinococcosis ; Humans ; Liver ; Male ; *Mesothelioma, Cystic/diagnosis/surgery ; Middle Aged ; Neoplasm Recurrence, Local ; }, abstract = {BACKGROUND: Benign Multicystic Peritoneal Mesothelioma (BMPM) is one of the rarest diseases in medicine with only more than 200 cases worldwide. This paper aims to report a case of Benign Multicystic Peritoneal Mesothelioma that strangely arose from the liver and was long treated as Hydatid cyst. The case also had many risk factors including asbestos exposure that had not yet been linked with Benign Multicystic Peritoneal Mesothelioma.

CASE PRESENTATION: We report a case of a 62 years old male with a history of a perforated peptic ulcer and a cystic mass in the liver that was misdiagnosed as hydatid cyst 7 years ago. He presented with generalized abdominal pain and bloating. Image studies showed many cystic formations filled with clear fluid. An en bloc surgery was performed and a pathologic study showed a multiloculated mass lined by flat or cuboidal epithelium leading to the diagnosis of BMPM. A follow up was scheduled after 3 months revealed total recurrence.

CONCLUSION: BMPM resembles many other cystic lesions in the abdomen and should be taken into consideration when dealing with nontypical cystic formations. Its diagnostic and treatment methods are still hazy making this disease difficult to approach.}, } @article {pmid34639316, year = {2021}, author = {Fazzo, L and Binazzi, A and Ferrante, D and Minelli, G and Consonni, D and Bauleo, L and Bruno, C and Bugani, M and De Santis, M and Iavarone, I and Magnani, C and Romeo, E and Zona, A and Alessi, M and Comba, P and Marinaccio, A}, title = {Burden of Mortality from Asbestos-Related Diseases in Italy.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {19}, pages = {}, pmid = {34639316}, issn = {1660-4601}, mesh = {*Asbestos/toxicity ; *Asbestosis ; Humans ; Italy/epidemiology ; *Mesothelioma ; *Occupational Diseases ; }, abstract = {Asbestos is one of the major worldwide occupational carcinogens. The global burden of asbestos-related diseases (ARDs) was estimated around 231,000 cases/year. Italy was one of the main European asbestos producers until the 1992 ban. The WHO recommended national programs, including epidemiological surveillance, to eliminate ARDs. The present paper shows the estimate of the burden of mortality from ARDs in Italy, established for the first time. National standardized rates of mortality from mesothelioma and asbestosis and their temporal trends, based on the National Institute of Statistics database, were computed. Deaths from lung cancer attributable to asbestos exposure were estimated using population-based case-control studies. Asbestos-related lung and ovarian cancer deaths attributable to occupational exposure were estimated, considering the Italian occupational cohort studies. In the 2010-2016 period, 4400 deaths/year attributable to asbestos were estimated: 1515 from mesothelioma, 58 from asbestosis, 2830 from lung and 16 from ovarian cancers. The estimates based on occupational cohorts showed that each year 271 deaths from mesothelioma, 302 from lung cancer and 16 from ovarian cancer were attributable to occupational asbestos exposure in industrial sectors with high asbestos levels. The important health impact of asbestos in Italy, 10-25 years after the ban, was highlighted. These results suggest the need for appropriate interventions in terms of prevention, health care and social security at the local level and could contribute to the global estimate of ARDs.}, } @article {pmid34639307, year = {2021}, author = {Kwon, SC and Lee, SS and Kang, MS and Huh, DA and Lee, YJ}, title = {The Epidemiologic Characteristics of Malignant Mesothelioma Cases in Korea: Findings of the Asbestos Injury Relief System from 2011-2015.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {19}, pages = {}, pmid = {34639307}, issn = {1660-4601}, mesh = {*Asbestos/toxicity ; Female ; Humans ; Incidence ; Italy ; Male ; *Mesothelioma/epidemiology ; *Mesothelioma, Malignant ; *Occupational Exposure ; Republic of Korea/epidemiology ; }, abstract = {(1) Background: The purpose of this study was to investigate the epidemiological characteristics of malignant mesothelioma in Korea by investigating cases compensated under the asbestos injury relief system. (2) Methods: A total of 407 compensated cases between 2011 and 2015 were reviewed using medical records and resident registrations in order to investigate the dates of diagnosis and death. Asbestos exposure and patients' general characteristics were investigated through face-to-face interviews. The standardized incidence ratio was calculated as the number of observations from 2005 to 2014 per exposure region in Korea, using the mid-annual population of each region in 2009 as the standard population. (3) Results: Among the 407 cases, 65.1% were male. The pleura and peritoneum were affected in 76.9% and 23.1% of cases, respectively. For peritoneal mesothelioma, the median survival duration was longer (p = 0.005), and the proportion of affected women was higher than that in pleural mesothelioma. The standardized incidence ratio (95% CI) by province of primary exposure was Chungnam 3.33 (2.51-4.35), Ulsan 1.85 (0.97-3.21), and Seoul 1.32 (1.06-1.63). (4) Conclusions: Although the representativeness of the data is limited, it is sufficient to assume the epidemiologic characteristics of malignant mesothelioma, help improve the compensation system, and contribute to future policies.}, } @article {pmid34638565, year = {2021}, author = {Yuen, ML and Zhuang, L and Rath, EM and Yu, T and Johnson, B and Sarun, KH and Wang, Y and Kao, S and Linton, A and Clarke, CJ and McCaughan, BC and Takahashi, K and Lee, K and Cheng, YY}, title = {The Role of E-Cadherin and microRNA on FAK Inhibitor Response in Malignant Pleural Mesothelioma (MPM).}, journal = {International journal of molecular sciences}, volume = {22}, number = {19}, pages = {}, pmid = {34638565}, issn = {1422-0067}, support = {2018//Regional Collaboration Program Grant/ ; }, mesh = {Aminopyridines/pharmacology ; Antigens, CD/*genetics/*metabolism ; Cadherins/*genetics/*metabolism ; Cell Cycle/drug effects ; Cell Line, Tumor ; ErbB Receptors/metabolism ; Focal Adhesion Kinase 1/*antagonists & inhibitors ; Humans ; Mesothelioma, Malignant/*drug therapy/*genetics ; MicroRNAs/genetics/metabolism/*physiology ; Protein Interaction Maps ; Protein Kinase Inhibitors/*pharmacology ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive malignancy with limited effective treatment options. Focal adhesion kinase (FAK) inhibitors have been shown to efficiently suppress MPM cell growth initially, with limited utility in the current clinical setting. In this study, we utilised a large collection of MPM cell lines and MPM tissue samples to study the role of E-cadherin (CDH1) and microRNA on the efficacy of FAK inhibitors in MPM. The immunohistochemistry (IHC) results showed that the majority of MPM FFPE samples exhibited either the absence of, or very low, E-cadherin protein expression in MPM tissue. We showed that MPM cells with high CDH1 mRNA levels exhibited resistance to the FAK inhibitor PND-1186. In summary, MPM cells that did not express CDH1 mRNA were sensitive to PND-1186, and MPM cells that retained CDH1 mRNA were resistant. A cell cycle analysis showed that PND-1186 induced cell cycle disruption by inducing the G2/M arrest of MPM cells. A protein-protein interaction study showed that EGFR is linked to the FAK pathway, and a target scan of the microRNAs revealed that microRNAs (miR-17, miR221, miR-222, miR137, and miR148) interact with EGFR 3'UTR. Transfection of MPM cells with these microRNAs sensitised the CHD1-expressing FAK-inhibitor-resistant MPM cells to the FAK inhibitor.}, } @article {pmid34612763, year = {2021}, author = {Korchevskiy, AA and Wylie, AG}, title = {Dimensional determinants for the carcinogenic potency of elongate amphibole particles.}, journal = {Inhalation toxicology}, volume = {33}, number = {6-8}, pages = {244-259}, doi = {10.1080/08958378.2021.1971340}, pmid = {34612763}, issn = {1091-7691}, mesh = {Asbestos, Amphibole/*adverse effects/chemistry ; Environmental Pollutants/*adverse effects ; Humans ; Lung Neoplasms/*chemically induced ; Mesothelioma/*chemically induced ; }, abstract = {CONTEXT: Carcinogenic properties of particulates depend, among other factors, on dimensional characteristics that affect their ability to reach sensitive tissue, to be removed or retained, and to interact with the cells.

OBJECTIVE: To model mesothelioma and lung cancer potency of amphibole particles based on their dimensional characteristics and mineral habit (asbestiform vs. nonasbestiform) utilizing epidemiological data and detailed size information.

METHODS: The datasets from recently created depository of dimensional information of elongate mineral particles were used to correlate mesothelioma and lung cancer potency with the fraction of particles in a specific size range and the ratio of length and width in different powers. In addition, the cancer potency factors were estimated and compared for 30 asbestiform, 15 nonasbestiform, and 10 mixed datasets.

RESULTS: For particles longer than 5 µm, the highest correlation with mesothelioma potency was achieved for width <0.22 µm, and with lung cancer <0.28 µm. The statistical power of the correlation was observed to lose significance at a maximum width of 0.6-0.7 µm. Mesothelioma potency correlated with length in the power of 1.9 divided by width in the power of 2.97, lung cancer potency with length in the power of 0.4 divided by width in the power of 1.17. The predicted cancer potencies of asbestiform, nonasbestiform, and mixed categories were significantly different.

CONCLUSION: While additional studies in this direction are warranted, this paper should serve as an additional confirmation for the role of fiber dimensions in the carcinogenicity of amphibole elongate mineral particles (EMPs).}, } @article {pmid34602383, year = {2022}, author = {Gupta, N and Soni, A and Mahajan, R and Selhi, P and Tyagi, R and Garg, B and Kaur, H}, title = {Peritoneal malignant mesothelioma: Slippery like an eel to diagnose on cytology-case series of 3 cases.}, journal = {Journal of the American Society of Cytopathology}, volume = {11}, number = {1}, pages = {40-45}, doi = {10.1016/j.jasc.2021.08.007}, pmid = {34602383}, issn = {2213-2945}, mesh = {Ascitic Fluid/cytology/pathology ; Cytological Techniques ; Diagnosis, Differential ; Humans ; Liver/cytology/pathology ; Male ; Mesothelioma, Malignant/*diagnosis/pathology ; Middle Aged ; Peritoneal Neoplasms/*diagnosis/pathology ; Peritoneum/cytology/pathology ; }, abstract = {INTRODUCTION: Peritoneal malignant mesothelioma is an extremely rare tumor and is a difficult diagnosis to be made on cytology alone. We report 3 cases where the cytologic features were misdiagnosed as carcinoma/lymphoma but histopathology and immunohistochemistry (IHC) established the diagnosis of malignant mesothelioma.

CLINICAL DETAILS: Case 1 was a 60-year-old man with multiloculated ascites and omental caking. Peritoneal fluid was reported as malignant on cytology but was misclassified as adenocarcinoma. Case 2, a 45-year-old man with ascites and peritoneal nodularity, radiologically mimicking peritoneal carcinomatosis, was also reported positive for malignancy on ascitic fluid cytology. Fine-needle aspiration (FNAC) from omental fat revealed signet ring cells, thus misleading to cytologic diagnosis of adenocarcinoma. Case 3 was a 63-year-old man with perisplenic mass with extensive omental caking and peritoneal nodularity that was also suspected to be peritoneal carcinomatosis on radiology. FNAC smears from perisplenic mass showed sheets of plasmacytoid cells. On cytology, the differential diagnoses offered were neuroendocrine tumor or non-Hodgkin lymphoma. The diagnosis of malignant mesothelioma was established only after IHC on histopathologic sections in all these cases. None of our patients had history of prior asbestos exposure.

CONCLUSION: In such clinical scenarios, with radiology suggesting peritoneal carcinomatosis, the cytologic features need corroboration by IHC/fluorescence in situ hybridization on cell block or biopsy to correctly identify malignant mesothelioma and differentiate it from metastatic carcinomatous deposits and benign mesothelial proliferation.}, } @article {pmid34590026, year = {2021}, author = {Nakagawa, K and Kijima, T and Okada, M and Morise, M and Kato, M and Hirano, K and Fujimoto, N and Takenoyama, M and Yokouchi, H and Ohe, Y and Hida, T and Aoe, K and Kishimoto, T and Hirokawa, M and Matsuki, H and Kaneko, Y and Yamada, T and Morimoto, C and Takeda, M}, title = {Phase 2 Study of YS110, a Recombinant Humanized Anti-CD26 Monoclonal Antibody, in Japanese Patients With Advanced Malignant Pleural Mesothelioma.}, journal = {JTO clinical and research reports}, volume = {2}, number = {6}, pages = {100178}, pmid = {34590026}, issn = {2666-3643}, abstract = {INTRODUCTION: YS110, a humanized monoclonal antibody with a high affinity to CD26, exhibited promising antitumor activity and was generally well-tolerated in the phase 1 part of a phase 1 and 2 Japanese trial in patients with malignant pleural mesothelioma (MPM). Here we report the results of the phase 2 part of the study.

METHODS: The patients included were aged 20 years and older, had histologically confirmed MPM, were refractory to or intolerant of existing antineoplastic agents, and were not candidates for standard therapy. YS110 6 mg/kg, determined in the phase 1 dose-determination part, was given in 6-weekly cycles (5 × once-weekly infusions, followed by a 1-wk rest).

RESULTS: The study included 31 patients (median age = 68 y, 90.3% men); 64.5% had stage IV MPM, 90.3% had greater than or equal to 20% CD26 expression in tumor tissue, and 38.7% (12 patients) had previously received nivolumab. The 6-month disease control rate was 3.2%. The best overall response was partial response in one patient and stable disease in 14 patients. The median progression-free survival was 2.8 months (both in patients who had and had not previously received nivolumab-groups A and B, respectively). Respective progression-free survival rates at 6 months were 9.1% and 31.6% in groups A and B. The median overall survival was 9.7 months. A total of 30 patients (96.8%) had at least one adverse event. Common treatment-related adverse events were infusion-related reaction (16.1%), hiccups (9.7%), and interstitial lung disease (9.7%). There were no treatment-related deaths.

CONCLUSIONS: The 6-month disease control rate did not exceed the predefined threshold, but YS110 revealed modest efficacy in response rate as salvage therapy in difficult-to-treat patients with MPM. YS110 was generally well tolerated.}, } @article {pmid34575358, year = {2021}, author = {Musso, V and Diotti, C and Palleschi, A and Tosi, D and Aiolfi, A and Mendogni, P}, title = {Management of Pleural Effusion Secondary to Malignant Mesothelioma.}, journal = {Journal of clinical medicine}, volume = {10}, number = {18}, pages = {}, pmid = {34575358}, issn = {2077-0383}, abstract = {Malignant pleural mesothelioma (MPM) is a highly aggressive pleural tumour which has been epidemiologically linked to occupational exposure to asbestos. MPM is often associated with pleural effusion, which is a common cause of morbidity and whose management remains a clinical challenge. In this review, we analysed the literature regarding the diagnosis and therapeutic options of pleural effusion secondary to mesothelioma. Our aim was to provide a comprehensive view on this subject, and a new algorithm was proposed as a practical aid to clinicians dealing with patients suffering from pleural effusion.}, } @article {pmid34572485, year = {2021}, author = {Štrbac, D and Dolžan, V}, title = {Matrix Metalloproteinases as Biomarkers and Treatment Targets in Mesothelioma: A Systematic Review.}, journal = {Biomolecules}, volume = {11}, number = {9}, pages = {}, pmid = {34572485}, issn = {2218-273X}, mesh = {Biomarkers, Tumor/*metabolism ; Body Fluids/metabolism ; Genetic Variation ; Humans ; Matrix Metalloproteinases/*metabolism ; Mesothelioma/*drug therapy/*enzymology/genetics ; *Molecular Targeted Therapy ; }, abstract = {Metalloproteinases (MMPs) have an important role in tissue remodeling and have been shown to have an effect on tumor progression, invasion, metastasis formation, and apoptosis in several tumors, including mesothelioma. Mesothelioma is a rare tumor arising from pleura and peritoneum and is frequently associated with asbestos exposure. We have performed a systematic search of PubMed.gov and ClinicalTrials.gov databases to retrieve and review three groups of studies: studies of MMPs expression in tumor tissue or body fluids in patients with mesothelioma, studies of MMPs genetic variability, and studies of MMPs as potential novel drug targets in mesothelioma. Several studies of MMPs in mesothelioma tissues reported a link between higher expression levels of commonly studied MMPs and clinical parameters, such as overall survival. Fewer studies have investigated genetic variability of MMP genes. Nevertheless, these studies suggested that certain genetic variants in MMP genes can have either protective or tumor-promoting effects on mesothelioma patients. MMPs have been also reported as novel drug targets, but so far no clinical trials of MMP inhibitors are registered in mesothelioma. In conclusion, MMPs play an important role in mesothelioma, but further studies are needed to elucidate the potentials of MMPs as biomarkers and drug targets in mesothelioma.}, } @article {pmid34566802, year = {2021}, author = {Di Basilio, D and Shigemura, J and Guglielmucci, F}, title = {Commentary: SARS-CoV-2 and Asbestos Exposure: Can Our Experience With Mesothelioma Patients Help Us Understand the Psychological Consequences of COVID-19 and Develop Interventions?.}, journal = {Frontiers in psychology}, volume = {12}, number = {}, pages = {720160}, pmid = {34566802}, issn = {1664-1078}, } @article {pmid34549571, year = {2021}, author = {Barbieri, PG and Calisti, R and Calabresi, C}, title = {[Pleural malignant mesotheliomas from environmental exposures to asbestos In Italy].}, journal = {Epidemiologia e prevenzione}, volume = {45}, number = {4}, pages = {289-295}, doi = {10.19191/EP21.4.P289.085}, pmid = {34549571}, issn = {1120-9763}, mesh = {*Asbestos/adverse effects ; Environmental Exposure/adverse effects ; Humans ; Italy/epidemiology ; *Mesothelioma/epidemiology/etiology ; *Mesothelioma, Malignant ; *Occupational Exposure/adverse effects ; *Pleural Neoplasms/epidemiology/etiology ; Sicily ; }, abstract = {Pleural mesothelioma clusters from outdoor environmental exposure have been highlighted also in Italy and, on the basis of epidemiological surveillance coordinated by the Italian National Mesothelioma Register, their frequency has been estimated at about 4.5%. Epidemiological studies and evaluations of some regional mesothelioma registers have made it possible to highlight that the dispersion of asbestos fibers in the outdoor environment was the only ascertained cause of mesothelioma in subjects from asbestos-cement factories, from the Balangero mine (Piedmont Region), from some serpentine rock quarries with tremolite outcrops in the Southern Apennines and in Alta Val di Susa (Piedmont Region); from chrysotile and serpentine caves in Valmalenco (Lombardy Region). Furthermore, cases of pleural mesothelioma were clearly caused by environmental pollution from fluoroedenite fibers in Biancavilla (Sicily Region). On the other hand, regional mesothelioma registers have also reported other circumstances of environmental asbestos exposure, like in the case of steel industry, shipbuilding, chemical plants, railway lines, and repair/demolition of railway carriages. However, these reports have not found confirmation on the basis of ad-hoc studies and it is likely that there is a lack of homogeneity in the assessment of individual cases. Apart from the scenarios which have been the subject of ad-hoc studies, the assessment of the causal role of environmental exposure to "in place" asbestos in the onset of pleural mesothelioma is problematic without an effort to more carefully examine the circumstances of possible exposure, harmonization of the attribution criteria used in the individual regional registers, analytical assessment of the impact of such exposure on the risk of onset of mesothelioma.}, } @article {pmid34540427, year = {2021}, author = {Khatib, S and Asad, O and Asad, H and Sabobeh, T}, title = {A Rare Case of Malignant Pleural Mesothelioma in a Young Healthy Male Without Asbestos Exposure.}, journal = {Cureus}, volume = {13}, number = {8}, pages = {e17199}, pmid = {34540427}, issn = {2168-8184}, abstract = {Malignant pleural mesothelioma (MPM) is a highly aggressive malignant tumor that arises from mesothelial cells of pleural cavity. The main risk factor for MPM is asbestos exposure with most cases discovered in elderly males after a long latency period. However, here we report a rare case of MPM diagnosed in a healthy young male patient without significant asbestos exposure. We report the case of an otherwise healthy 47-year-old male who presented with one week of exertional dyspnea and chest pain. Chest X-ray showed unilateral large pleural effusion. Chest CT scan revealed confluent right hilar mass and pleural thickening. Pleural fluid analysis showed exudative features. Cytology was negative for malignant cells. Core tissue biopsy showed features of epithelioid mesothelioma. Although most cases of MPM have been reported in elderly male patients with significant asbestos exposure, more research is needed to explain the pathogenesis of MPM in young patients without asbestos exposure.}, } @article {pmid34526026, year = {2021}, author = {Airoldi, C and Magnani, C and Lazzarato, F and Mirabelli, D and Tunesi, S and Ferrante, D}, title = {Environmental asbestos exposure and clustering of malignant mesothelioma in community: a spatial analysis in a population-based case-control study.}, journal = {Environmental health : a global access science source}, volume = {20}, number = {1}, pages = {103}, pmid = {34526026}, issn = {1476-069X}, mesh = {Aged ; Asbestos/*adverse effects ; Case-Control Studies ; Cluster Analysis ; Environmental Exposure/*adverse effects ; Female ; Humans ; Italy/epidemiology ; Male ; Mesothelioma, Malignant/*epidemiology ; Middle Aged ; Pleural Neoplasms/*epidemiology ; Spatial Analysis ; }, abstract = {BACKGROUND: Neighborhood exposure to asbestos increases the risk of developing malignant mesothelioma (MM) in residents who live near asbestos mines and asbestos product plants. The area of Casale Monferrato (Northwest Italy) was impacted by several sources of asbestos environmental pollution, due to the presence of the largest Italian asbestos cement (AC) plant. In the present study, we examined the spatial variation of MM risk in an area with high levels of asbestos pollution and secondly, and we explored the pattern of clustering.

METHODS: A population-based case-control study conducted between 2001 and 2006 included 200 cases and 348 controls. Demographic and occupational data along with residential information were recorded. Bivariate Kernel density estimation was used to map spatial variation in disease risk while an adjusted logistic model was applied to estimate the impact of residential distance from the AC plant. Kulldorf test and Cuzick Edward test were then performed.

RESULTS: One hundred ninety-six cases and 322 controls were included in the analyses. The contour plot of the cases to controls ratio showed a well-defined peak of MM incidence near the AC factory, and the risk decreased monotonically in all directions when large bandwidths were used. However, considering narrower smoothing parameters, several peaks of increased risk were reported. A constant trend of decreasing OR with increasing distance was observed, with estimates of 10.9 (95% CI 5.32-22.38) and 10.48 (95%CI 4.54-24.2) for 0-5 km and 5-10 km, respectively (reference > 15 km). Finally, a significant (p < 0.0001) excess of cases near the pollution source was identified and cases are spatially clustered relative to the controls until 13 nearest neighbors.

CONCLUSIONS: In this study, we found an increasing pattern of mesothelioma risk in the area around a big AC factory and we detected secondary clusters of cases due to local exposure points, possibly associated to the use of asbestos materials.}, } @article {pmid34519165, year = {2021}, author = {Torkki, P and Paajanen, J and Kytö, V and Laaksonen, S and Räsänen, J and Myllärniemi, M and Ilonen, I}, title = {Evidence for marked underutilization of insurance billing in malignant pleural mesothelioma in Finland.}, journal = {Thoracic cancer}, volume = {12}, number = {19}, pages = {2594-2600}, pmid = {34519165}, issn = {1759-7714}, mesh = {Finland ; Health Care Costs/*statistics & numerical data ; Humans ; Insurance, Health/*statistics & numerical data ; Mesothelioma, Malignant/*economics/*therapy ; Retrospective Studies ; }, abstract = {BACKGROUND: Substantial variation in health care costs for malignant pleural mesothelioma (MPM) has previously been identified.

MATERIALS AND METHODS: We analyzed the changes in health care costs in MPM in Finland during 2002-2012. Finland has low-threshold public health care and a mandatory Workers' Compensation scheme that covers all occupational-related disease expenses. The costs include treatment costs for inpatients, hospice care, medication costs, rehabilitation costs, and travel costs. All costs are expressed in 2012 prices, adjusted using the consumer price index.

RESULTS: A total of 907 MPM patients were included in the study. Mean duration of inpatient episodes increased 7% per year from 2002 to 2012, correlating with total costs (R[2]  = 0.861, p < 0.05). The annual total costs for treatment increased from 1.7 to 4.3 m€ during the study period and the cost per patient from 27 000 to 43 000 €. The overall costs increased progressively by the number of procedures performed. In patients who had been compensated for occupational cause by Workers' Compensation Center, only 36% of the overall care costs were billed from the insurance company. Billing of inpatient costs was 86% in these patients.

CONCLUSION: During the study period, we found that the costs of MPM increased more than the average health care costs. This may be because of advanced diagnostic workup or more costly treatment (e.g., pemetrexed). Moreover, only one-third of all health care costs are charged to Workers' Compensation Insurance.}, } @article {pmid34511983, year = {2021}, author = {Xie, D and Hu, J and Wu, T and Cao, K and Luo, X}, title = {Four Immune-Related Genes (FN1, UGCG, CHPF2 and THBS2) as Potential Diagnostic and Prognostic Biomarkers for Carbon Nanotube-Induced Mesothelioma.}, journal = {International journal of general medicine}, volume = {14}, number = {}, pages = {4987-5003}, pmid = {34511983}, issn = {1178-7074}, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM), a highly aggressive cancer, was mainly attributed to asbestos exposure. Carbon nanotubes (CNTs) share similar negative features to asbestos, provoking concerns about their contribution to MPM. This study was used to identify genes associated with CNT-induced MPM.

METHODS: Microarray datasets were available in the Gene Expression Omnibus database. The limma method was used to identify differentially expressed genes (DEGs) in CNT-exposed MeT5A cells (GSE48855) or mice (GSE51636). Weighted correlation network analysis (WGCNA) and protein-protein interaction (PPI) network construction were conducted to screen hub DEGs. The mRNA expression levels of hub DEGs were validated on MPM samples of GSE51024, GSE2549 and GSE42977 datasets, and their diagnostic efficacy was determined by receiver operating characteristic curve analysis. The prognostic values of hub DEGs were assessed using online tools based on The Cancer Genome Atlas data. Their functions were annotated by Database for Annotation, Visualization and Integrated Discovery (DAVID) enrichment and correlation with immune cells and markers.

RESULTS: WGCNA identified that two modules were associated with disease status. Thirty-one common DEGs in the GSE48855 and GSE51636 datasets were overlapped with the genes in these two modules. Twenty of them had a high degree centrality (≥4) in the PPI network. Four DEGs (FN1, fibronectin 1; UGCG, UDP-glucose ceramide glucosyltransferase; CHPF2, chondroitin polymerizing factor 2; and THBS2, thrombospondin 2) could predict the overall survival, and they were confirmed to be upregulated in MPM samples compared with controls. Also, they could effectively predict the MPM risk, with an overall accuracy of >0.9. DAVID analysis revealed FN1, CHPF2 and THBS2 functioned in cell-ECM interactions; UGCG influenced glycosphingolipid metabolism. All genes were positively associated with infiltrating levels of immune cells (macrophages or dendritic cells) and the expression of the dendritic cell marker (NRP1, neuropilin 1).

CONCLUSION: These four immune-related genes represent potential biomarkers for monitoring CNT-induced MPM and predicting the prognosis.}, } @article {pmid34491782, year = {2022}, author = {Nowak, AK and Jackson, A and Sidhu, C}, title = {Management of Advanced Pleural Mesothelioma-At the Crossroads.}, journal = {JCO oncology practice}, volume = {18}, number = {2}, pages = {116-124}, doi = {10.1200/OP.21.00426}, pmid = {34491782}, issn = {2688-1535}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Humans ; *Mesothelioma/drug therapy/etiology ; *Mesothelioma, Malignant ; Nivolumab/therapeutic use ; *Pleural Neoplasms/drug therapy/pathology ; }, abstract = {The management of pleural mesothelioma has changed with the demonstration that first-line checkpoint blockade therapy improves survival. This review covers issues of relevance to the practicing medical oncologist, with an emphasis on the palliative setting and on new information. Until recently, standard systemic therapy for mesothelioma was combination chemotherapy with platinum and pemetrexed. In 2020, combination immunotherapy with ipilimumab and nivolumab was approved as first-line systemic therapy for mesothelioma following release of the results from the CheckMate 743 trial. This trial showed improved overall survival for patients receiving ipilimumab and nivolumab over those treated with platinum and pemetrexed chemotherapy. When the survival results were examined by histologic subtype, the survival benefit was most significant in those with nonepithelioid mesothelioma, a group for which combination immunotherapy is now standard of care. The most important outstanding issue from CheckMate-743 is a better understanding, through translational studies, of which patients with epithelioid mesothelioma may benefit from combination immunotherapy. The next generation of first-line clinical trials in mesothelioma will report the results of first-line combination chemoimmunotherapy. For those patients who receive first-line dual checkpoint blockade, there is no evidence as to the efficacy of subsequent chemotherapy. However, given the known first-line efficacy of cisplatin or carboplatin and pemetrexed, combination chemotherapy is an appropriate subsequent choice for those who progress on or after dual immunotherapy. For those who previously received chemotherapy without immunotherapy, single-agent nivolumab provides benefit over best supportive care. In summary, both chemotherapy and immunotherapy should be considered for all patients during their disease course. Another topical issue is the growing appreciation that some individuals have an inherited predisposition to mesothelioma; referral to a clinical geneticist should be considered under some circumstances. The role of surgery and multimodality therapy is controversial, with results awaited from the fully recruited MARS-2 clinical trial. Patient selection, staging, and multidisciplinary review are critical to identify those who might benefit from a multimodality approach. Finally, a proactive, multidisciplinary approach to symptom management and the principles of management of pleural effusions are critical to manage the symptom burden of mesothelioma and optimize patient well-being.}, } @article {pmid34487023, year = {2022}, author = {Dick, IM and Lee, YCG and Cheah, HM and Miranda, A and Robinson, BWS and Creaney, J}, title = {Profile of soluble factors in pleural effusions predict prognosis in mesothelioma.}, journal = {Cancer biomarkers : section A of Disease markers}, volume = {33}, number = {1}, pages = {159-169}, pmid = {34487023}, issn = {1875-8592}, mesh = {Biomarkers, Tumor/metabolism ; Humans ; *Lung Neoplasms/metabolism ; *Mesothelioma/diagnosis/metabolism ; *Pleural Effusion/diagnosis ; *Pleural Effusion, Malignant/diagnosis ; *Pleural Neoplasms/diagnosis ; Prognosis ; }, abstract = {BACKGROUND: Pleural mesothelioma is a deadly asbestos induced cancer. Less than 10% of mesothelioma patients survive 5 years post diagnosis. However survival can range from a few months to a number of years. Accurate prediction of survival is important for patients to plan for their remaining life, and for clinicians to determine appropriate therapy. One unusual feature of mesothelioma is that patients frequently present with tumor-associated pleural effusions early in the course of the disease.

OBJECTIVE: To study whether cells and molecules present in pleural effusions provide prognostic information for mesothelioma.

METHODS: We profiled the cellular constituents and concentrations of 40 cytokines, chemokines and cellular factors (collectively "soluble factors") involved in inflammatory and immune signalling pathways in pleural effusion samples from 50 mesothelioma patients.Associations with survival were evaluated by Cox proportional hazards regression methods. Results for the two soluble factors most significantly and independently associated with survival were validated in an independent set of samples (n= 51) using a separate assay system.

RESULTS: Survival analysis revealed that IL8, IL2Ra (CD25) and PF4 were independent determinants of a more negative prognosis in mesothelioma patients, independent of other known prognostic factors. Lipocalin2 and IL4 were associated with better prognosis.

CONCLUSIONS: This study demonstrates that pleural effusions rich in a range of soluble factors are associated with poor prognosis. These findings will enhance our ability to prognosticate outcomes in mesothelioma patients.}, } @article {pmid34445720, year = {2021}, author = {Lisini, D and Lettieri, S and Nava, S and Accordino, G and Frigerio, S and Bortolotto, C and Lancia, A and Filippi, AR and Agustoni, F and Pandolfi, L and Piloni, D and Comoli, P and Corsico, AG and Stella, GM}, title = {Local Therapies and Modulation of Tumor Surrounding Stroma in Malignant Pleural Mesothelioma: A Translational Approach.}, journal = {International journal of molecular sciences}, volume = {22}, number = {16}, pages = {}, pmid = {34445720}, issn = {1422-0067}, support = {#08050//IRCCS Policlinico San Mattteo/ ; }, mesh = {Combined Modality Therapy ; Drug Delivery Systems/methods ; Humans ; Immunotherapy/methods ; Mesothelioma/pathology/therapy ; Mesothelioma, Malignant/*pathology/*therapy ; Pleural Neoplasms/pathology/therapy ; Soft Tissue Neoplasms/pathology/therapy ; Tumor Microenvironment/drug effects/physiology ; }, abstract = {Malignant Pleural Mesothelioma (MPM) is a rare and aggressive neoplasm of the pleural mesothelium, mainly associated with asbestos exposure and still lacking effective therapies. Modern targeted biological strategies that have revolutionized the therapy of other solid tumors have not had success so far in the MPM. Combination immunotherapy might achieve better results over chemotherapy alone, but there is still a need for more effective therapeutic approaches. Based on the peculiar disease features of MPM, several strategies for local therapeutic delivery have been developed over the past years. The common rationale of these approaches is: (i) to reduce the risk of drug inactivation before reaching the target tumor cells; (ii) to increase the concentration of active drugs in the tumor micro-environment and their bioavailability; (iii) to reduce toxic effects on normal, non-transformed cells, because of much lower drug doses than those used for systemic chemotherapy. The complex interactions between drugs and the local immune-inflammatory micro-environment modulate the subsequent clinical response. In this perspective, the main interest is currently addressed to the development of local drug delivery platforms, both cell therapy and engineered nanotools. We here propose a review aimed at deep investigation of the biologic effects of the current local therapies for MPM, including cell therapies, and the mechanisms of interaction with the tumor micro-environment.}, } @article {pmid34444165, year = {2021}, author = {Lemen, RA and Landrigan, PJ}, title = {Sailors and the Risk of Asbestos-Related Cancer.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {16}, pages = {}, pmid = {34444165}, issn = {1660-4601}, mesh = {*Asbestos/analysis/toxicity ; Asbestos, Serpentine ; Humans ; *Mesothelioma/chemically induced/epidemiology ; *Military Personnel ; Ships ; }, abstract = {Sailors have long been known to experience high rates of injury, disease, and premature death. Many studies have shown asbestos-related diseases among shipyard workers, but few have examined the epidemiology of asbestos-related disease and death among asbestos-exposed sailors serving on ships at sea. Chrysotile and amphibole asbestos were used extensively in ship construction for insulation, joiner bulkhead systems, pipe coverings, boilers, machinery parts, bulkhead panels, and many other uses, and asbestos-containing ships are still in service. Sailors are at high risk of exposure to shipboard asbestos, because unlike shipyard workers and other occupationally exposed groups, sailors both work and live at their worksite, making asbestos standards and permissible exposure limits (PELs). based on an 8-h workday inadequate to protect their health elevated risks of mesothelioma and other asbestos-related cancers have been observed among sailors through epidemiologic studies. We review these studies here.}, } @article {pmid34439349, year = {2021}, author = {Brims, F}, title = {Epidemiology and Clinical Aspects of Malignant Pleural Mesothelioma.}, journal = {Cancers}, volume = {13}, number = {16}, pages = {}, pmid = {34439349}, issn = {2072-6694}, abstract = {Mesothelioma is a cancer predominantly of the pleural cavity. There is a clear association of exposure to asbestos with a dose dependent risk of mesothelioma. The incidence of mesothelioma in different countries reflect the historical patterns of commercial asbestos utilisation in the last century and predominant occupational exposures mean that mesothelioma is mostly seen in males. Modern imaging techniques and advances in immunohistochemical staining have contributed to an improved diagnosis of mesothelioma. There have also been recent advances in immune checkpoint inhibition, however, mesothelioma remains very challenging to manage, especially considering its limited response to conventional systemic anticancer therapy and that no cure exists. Palliative interventions and support remain paramount with a median survival of 9-12 months after diagnosis. The epidemiology and diagnosis of mesothelioma has been debated over previous decades, due to a number of factors, such as the long latent period following asbestos exposure and disease occurrence, the different potencies of the various forms of asbestos used commercially, the occurrence of mesothelioma in the peritoneal cavity and its heterogeneous pathological and cytological appearances. This review will describe the contemporary knowledge on the epidemiology of mesothelioma and provide an overview of the best clinical practice including diagnostic approaches and management.}, } @article {pmid34439164, year = {2021}, author = {Carbotti, G and Dozin, B and Martini, S and Giordano, C and Scordamaglia, F and Croce, M and Filaci, G and Ferrini, S and Fabbi, M}, title = {IL-27 Mediates PD-L1 Expression and Release by Human Mesothelioma Cells.}, journal = {Cancers}, volume = {13}, number = {16}, pages = {}, pmid = {34439164}, issn = {2072-6694}, support = {GR-2013-02356568//Italian Ministry of Health/ ; 5 x 1000 Funds//Italian Ministry of Health/ ; Ricerca Corrente 2018-2021//Italian Ministry of Health/ ; }, abstract = {Malignant mesothelioma (MM) is a rare tumor with an unfavorable prognosis. MM genesis involves asbestos-mediated local inflammation, supported by several cytokines, including IL-6. Recent data showed that targeting PD-1/PD-L1 is an effective therapy in MM. Here, we investigated the effects of IL-6 trans-signaling and the IL-6-related cytokine IL-27 on human MM cells in vitro by Western blot analysis of STAT1/3 phosphorylation. The effects on PD-L1 expression were tested by qRT-PCR and flow-cytometry and the release of soluble (s)PD-L1 by ELISA. We also measured the concentrations of sPD-L1 and, by multiplexed immunoassay, IL-6 and IL-27 in pleural fluids obtained from 77 patients in relation to survival. IL-27 predominantly mediates STAT1 phosphorylation and increases PD-L1 gene and surface protein expression and sPD-L1 release by human MM cells in vitro. IL-6 has limited activity, whereas a sIL-6R/IL-6 chimeric protein mediates trans-signaling predominantly via STAT3 phosphorylation but has no effect on PD-L1 expression and release. IL-6, IL-27, and sPD-L1 are present in pleural fluids and show a negative correlation with overall survival, but only IL-27 shows a moderate albeit significant correlation with sPD-L1 levels. Altogether these data suggest a potential role of IL-27 in PD-L1-driven immune resistance in MM.}, } @article {pmid34430345, year = {2021}, author = {Mathilakathu, A and Borchert, S and Wessolly, M and Mairinger, E and Beckert, H and Steinborn, J and Hager, T and Christoph, DC and Kollmeier, J and Wohlschlaeger, J and Mairinger, T and Schmid, KW and Walter, RFH and Brcic, L and Mairinger, FD}, title = {Mitogen signal-associated pathways, energy metabolism regulation, and mediation of tumor immunogenicity play essential roles in the cellular response of malignant pleural mesotheliomas to platinum-based treatment: a retrospective study.}, journal = {Translational lung cancer research}, volume = {10}, number = {7}, pages = {3030-3042}, pmid = {34430345}, issn = {2218-6751}, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare malignant tumor associated with asbestos exposure, with infaust prognosis and overall survival below 20 months in treated patients. Platinum is still the backbone of the chemotherapy protocols, and the reasons for the rather poor efficacy of platinum compounds in MPM remain largely unknown. Therefore, we aimed to analyze differences in key signaling pathways and biological mechanisms in therapy-naïve samples and samples after chemotherapy in order to evaluate the effect of platinum-based chemotherapy.

METHODS: The study cohort comprised 24 MPM tumor specimens, 12 from therapy-naïve and 12 from patients after platinum-based therapy. Tumor samples were screened using the NanoString nCounter platform for digital gene expression analysis with an appurtenant custom-designed panel comprising a total of 366 mRNAs covering the most important tumor signaling pathways. Significant pathway associations were identified by gene set enrichment analysis using the WEB-based GEne SeT AnaLysis Toolkit (WebGestalt).

RESULTS: We have found reduced activity of TNF (normalized enrichment score: 2.03), IL-17 (normalized enrichment score: 1.93), MAPK (normalized enrichment score: 1.51), and relaxin signaling pathways (normalized enrichment score: 1.42) in the samples obtained after platinum-based therapy. In contrast, AMPK (normalized enrichment score: -1.58), mTOR (normalized enrichment score: -1.50), Wnt (normalized enrichment score: -1.38), and longevity regulating pathway (normalized enrichment score: -1.31) showed significantly elevated expression in the same samples.

CONCLUSIONS: We could identify deregulated signaling pathways due to a directed cellular response to platinum-induced cell stress. Our results are paving the ground for a better understanding of cellular responses and escape mechanisms, carrying a high potential for improved clinical management of patients with MPM.}, } @article {pmid34395196, year = {2021}, author = {Tran, T and Egilman, D and Rigler, M and Emory, T}, title = {A Critique of Helsinki Criteria for Using Lung Fiber Levels to Determine Causation in Mesothelioma Cases.}, journal = {Annals of global health}, volume = {87}, number = {1}, pages = {73}, pmid = {34395196}, issn = {2214-9996}, mesh = {Air Pollutants, Occupational/*adverse effects ; Asbestos/*toxicity ; Humans ; Lung/*pathology ; Lung Neoplasms/*chemically induced/epidemiology ; Mesothelioma, Malignant/*chemically induced/epidemiology ; Mineral Fibers/*analysis/toxicity ; Occupational Exposure/*adverse effects/analysis ; Particulate Matter/analysis/chemistry ; }, abstract = {Asbestos is a known human carcinogen and the chief known cause of mesothelioma. In 1997, a group of experts developed the Helsinki Criteria, which established criteria for attribution of mesothelioma to asbestos. The criteria include two methods for causation attribution: 1) a history of significant occupational, domestic, or environmental exposure and/or 2) pathologic evidence of exposure to asbestos. In 2014, the Helsinki Criteria were updated, and these attribution criteria were not changed. However, since the Helsinki Criteria were first released in 1997, some pathologists, cell biologists, and others have claimed that a history of exposure cannot establish causation unless the lung asbestos fiber burden exceeds "the background range for the laboratory in question to attribute mesothelioma cases to exposure to asbestos." This practice ignores the impact on fiber burden of clearance/translocation over time, which in part is why the Helsinki Criteria concluded that a history of exposure to asbestos was independently sufficient to attribute causation to asbestos. After reviewing the Helsinki Criteria, we conclude that their methodology is fatally flawed because a quantitative assessment of a background lung tissue fiber level cannot be established. The flaws of the Helsinki Criteria are both technical and substantive. The 1995 paper that served as the scientific basis for establishing background levels used inconsistent methods to determine exposures in controls and cases. In addition, historic controls cannot be used to establish background fiber levels for current cases because ambient exposures to asbestos have decreased over time and control cases pre-date current cases by decades. The use of scanning electron microscope (SEM) compounded the non-compatibility problem; the applied SEM cannot distinguish talc from anthophyllite because it cannot perform selected area electron diffraction, which is a crucial identifier in ATEM for distinguishing the difference between serpentine asbestos, amphibole asbestos, and talc.}, } @article {pmid34390717, year = {2022}, author = {Ciocan, C and Pira, E and Coggiola, M and Franco, N and Godono, A and La Vecchia, C and Negri, E and Boffetta, P}, title = {Mortality in the cohort of talc miners and millers from Val Chisone, Northern Italy: 74 years of follow-up.}, journal = {Environmental research}, volume = {203}, number = {}, pages = {111865}, doi = {10.1016/j.envres.2021.111865}, pmid = {34390717}, issn = {1096-0953}, mesh = {Cause of Death ; Follow-Up Studies ; Humans ; Italy/epidemiology ; Male ; *Occupational Exposure ; *Talc/toxicity ; }, abstract = {OBJECTIVE: To update the analysis of mortality of a cohort of talc miners and millers in Northern Italy.

METHODS: We analyzed overall mortality and mortality from specific causes of death during 1946-2020 of 1749 male workers in a talc mine where asbestos was not detected (1184 miners and 565 millers) employed during 1946-1995.

RESULTS: The overall standardized mortality ratio (SMR) was 1.21 (95 % confidence interval [CI] 1.14-1.28); no deaths were observed from pleural cancer. Mortality from lung cancer was not increased (SMR = 1.02 95 % CI 0.82-1.27), while mortality from pneumoconiosis was (SMR 9.55; 95 % CI 7.43-12.08), especially among miners (SMR 12.74; 95 % CI 9.79-16.31). There was a trend in risk of pneumoconiosis with increasing duration of employment in the overall cohort, and the SMR for 25+ years of employment was 15.12 (95 % CI 10.89-20.43).

CONCLUSIONS: This uniquely long-term follow up confirms the results of previous analyses, namely the lack of association between exposure to talc with no detectable level of asbestos and lung cancer and mesothelioma. Increased mortality from pneumoconiosis among miners is related to past exposure to silica.}, } @article {pmid34389715, year = {2021}, author = {Grosso, S and Marini, A and Gyuraszova, K and Voorde, JV and Sfakianos, A and Garland, GD and Tenor, AR and Mordue, R and Chernova, T and Morone, N and Sereno, M and Smith, CP and Officer, L and Farahmand, P and Rooney, C and Sumpton, D and Das, M and Teodósio, A and Ficken, C and Martin, MG and Spriggs, RV and Sun, XM and Bushell, M and Sansom, OJ and Murphy, D and MacFarlane, M and Le Quesne, JPC and Willis, AE}, title = {The pathogenesis of mesothelioma is driven by a dysregulated translatome.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {4920}, pmid = {34389715}, issn = {2041-1723}, support = {MC_UU_00025/6/MRC_/Medical Research Council/United Kingdom ; MR/K00252X/1/MRC_/Medical Research Council/United Kingdom ; MC_UU_00025/4/MRC_/Medical Research Council/United Kingdom ; /DH_/Department of Health/United Kingdom ; MC_UP_A600_1023/MRC_/Medical Research Council/United Kingdom ; 5TR019/MRC_/Medical Research Council/United Kingdom ; 28879/CRUK_/Cancer Research UK/United Kingdom ; MC_UP_1203/1/MRC_/Medical Research Council/United Kingdom ; A17196/CRUK_/Cancer Research UK/United Kingdom ; 5TR00/MRC_/Medical Research Council/United Kingdom ; MCA/600/MRC_/Medical Research Council/United Kingdom ; PCL/18/06/CSO_/Chief Scientist Office/United Kingdom ; MC_EX_G0902052/MRC_/Medical Research Council/United Kingdom ; 24388/CRUK_/Cancer Research UK/United Kingdom ; MC_UP_A600_1024/MRC_/Medical Research Council/United Kingdom ; 29372/CRUK_/Cancer Research UK/United Kingdom ; 21139/CRUK_/Cancer Research UK/United Kingdom ; MC_UU_00025/5/MRC_/Medical Research Council/United Kingdom ; A29252/CRUK_/Cancer Research UK/United Kingdom ; 30062/CRUK_/Cancer Research UK/United Kingdom ; A21139/CRUK_/Cancer Research UK/United Kingdom ; MC_UU_00025/7/MRC_/Medical Research Council/United Kingdom ; 29252/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Animals ; Asbestos ; Humans ; Mechanistic Target of Rapamycin Complex 1/antagonists & inhibitors/metabolism ; Mechanistic Target of Rapamycin Complex 2/antagonists & inhibitors/metabolism ; Mesothelioma, Malignant/chemically induced/*genetics/metabolism ; Mice, Inbred C57BL ; Mice, Knockout ; Mitochondria/genetics/metabolism ; Naphthyridines/pharmacology ; Oncogenes/*genetics ; Polyribosomes/drug effects/metabolism ; Protein Biosynthesis/drug effects/*genetics ; RNA, Messenger/*genetics/metabolism ; Tumor Cells, Cultured ; Mice ; }, abstract = {Malignant mesothelioma (MpM) is an aggressive, invariably fatal tumour that is causally linked with asbestos exposure. The disease primarily results from loss of tumour suppressor gene function and there are no 'druggable' driver oncogenes associated with MpM. To identify opportunities for management of this disease we have carried out polysome profiling to define the MpM translatome. We show that in MpM there is a selective increase in the translation of mRNAs encoding proteins required for ribosome assembly and mitochondrial biogenesis. This results in an enhanced rate of mRNA translation, abnormal mitochondrial morphology and oxygen consumption, and a reprogramming of metabolic outputs. These alterations delimit the cellular capacity for protein biosynthesis, accelerate growth and drive disease progression. Importantly, we show that inhibition of mRNA translation, particularly through combined pharmacological targeting of mTORC1 and 2, reverses these changes and inhibits malignant cell growth in vitro and in ex-vivo tumour tissue from patients with end-stage disease. Critically, we show that these pharmacological interventions prolong survival in animal models of asbestos-induced mesothelioma, providing the basis for a targeted, viable therapeutic option for patients with this incurable disease.}, } @article {pmid34386422, year = {2021}, author = {Zhang, C and Wu, L and de Perrot, M and Zhao, X}, title = {Carbon Nanotubes: A Summary of Beneficial and Dangerous Aspects of an Increasingly Popular Group of Nanomaterials.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {693814}, pmid = {34386422}, issn = {2234-943X}, abstract = {Carbon nanotubes (CNTs) are nanomaterials with broad applications that are produced on a large scale. Animal experiments have shown that exposure to CNTs, especially one type of multi-walled carbon nanotube, MWCNT-7, can lead to malignant transformation. CNTs have characteristics similar to asbestos (size, shape, and biopersistence) and use the same molecular mechanisms and signaling pathways as those involved in asbestos tumorigenesis. Here, a comprehensive review of the characteristics of carbon nanotubes is provided, as well as insights that may assist in the design and production of safer nanomaterials to limit the hazards of currently used CNTs.}, } @article {pmid34379126, year = {2021}, author = {Zhai, Z and Ruan, J and Zheng, Y and Xiang, D and Li, N and Hu, J and Shen, J and Deng, Y and Yao, J and Zhao, P and Wang, S and Yang, S and Zhou, L and Wu, Y and Xu, P and Lyu, L and Lyu, J and Bergan, R and Chen, T and Dai, Z}, title = {Assessment of Global Trends in the Diagnosis of Mesothelioma From 1990 to 2017.}, journal = {JAMA network open}, volume = {4}, number = {8}, pages = {e2120360}, pmid = {34379126}, issn = {2574-3805}, mesh = {Age Factors ; Cross-Sectional Studies ; Forecasting ; Geography ; Global Burden of Disease/*history/*trends ; Global Health/*statistics & numerical data/*trends ; History, 20th Century ; History, 21st Century ; Humans ; Incidence ; Mesothelioma/*diagnosis/*epidemiology/*history ; Prevalence ; Sex Factors ; Socioeconomic Factors ; }, abstract = {IMPORTANCE: It is difficult for policy makers and clinicians to formulate targeted management strategies for mesothelioma because data on current epidemiological patterns worldwide are lacking.

OBJECTIVE: To evaluate the mesothelioma burden across the world and describe its epidemiological distribution over time and by sociodemographic index (SDI) level, geographic location, sex, and age.

Annual case data and age-standardized rates of incidence, death, and disability-adjusted life-years associated with mesothelioma among different age groups were obtained from the Global Burden of Disease 2017 database. The estimated annual percentage changes in age-standardized rates were calculated to evaluate temporal trends in incidence and mortality. The study population comprised individuals from 21 regions in 195 countries and territories who were diagnosed with mesothelioma between 1990 and 2017. Data were collected from May 23, 2019, to January 18, 2020.

MAIN OUTCOMES AND MEASURES: Primary outcomes were incident cases, deaths, and their age-standardized rates and estimated annual percentage changes. Secondary outcomes were disability-adjusted life-years and relative temporal trends.

RESULTS: Overall, 34 615 new cases (95% uncertainty interval [UI], 33 530-35 697 cases) of mesothelioma and 29 909 deaths (95% UI, 29 134-30 613 deaths) associated with mesothelioma were identified in 2017, and more than 70% of these cases and deaths were among male individuals. In 1990, the number of incident cases was 21 224 (95% UI, 17 503-25 450), and the number of deaths associated with mesothelioma was 17 406 (95% UI, 14 495-20 660). These numbers increased worldwide from 1990 to 2017, with more than 50% of cases recorded in regions with high SDI levels, whereas the age-standardized incidence rate (from 0.52 [95% UI, 0.43-0.62] in 1990 to 0.44 [95% UI, 0.42-0.45] in 2017) and the age-standardized death rate (from 0.44 [95% UI, 0.37-0.52] in 1990 to 0.38 [95% UI, 0.37-0.39] in 2017) decreased, with estimated annual percentage changes of -0.61 (95% CI, -0.67 to -0.54) for age-standardized incidence rate and -0.44 (95% CI, -0.52 to -0.37) for age-standardized death rate. The proportion of incident cases among those 70 years or older continued to increase (from 36.49% in 1990 to 44.67% in 2017), but the proportion of patients younger than 50 years decreased (from 16.74% in 1990 to 13.75% in 2017) over time. In addition, mesothelioma incident cases and age-standardized incidence rates began to decrease after 20 years of a complete ban on asbestos use. For example, in Italy, a complete ban on asbestos went into effect in 1992; incident cases increased from 1409 individuals (95% UI, 1013-1733 individuals) in 1990, peaked in 2015 after 23 years of the asbestos ban, then decreased from 1820 individuals (95% UI, 1699-1981 individuals) in 2015 to 1746 individuals (95% UI, 1555-1955 individuals) in 2017.

CONCLUSIONS AND RELEVANCE: This cross-sectional study found that incident cases of mesothelioma and deaths associated with mesothelioma continuously increased worldwide, especially in resource-limited regions with low SDI levels. Based on these findings, global governments and medical institutions may consider formulating optimal policies and strategies for the targeted prevention and management of mesothelioma.}, } @article {pmid34373297, year = {2021}, author = {Ferrante, P}, title = {Hospitalisation costs of malignant mesothelioma: results from the Italian hospital discharge registry (2001-2018).}, journal = {BMJ open}, volume = {11}, number = {8}, pages = {e046456}, pmid = {34373297}, issn = {2044-6055}, mesh = {*Asbestos/adverse effects ; Hospitalization ; Hospitals ; Humans ; Incidence ; Italy/epidemiology ; *Mesothelioma/epidemiology/therapy ; *Mesothelioma, Malignant ; *Occupational Exposure ; Patient Discharge ; *Pleural Neoplasms ; Registries ; Retrospective Studies ; }, abstract = {OBJECTIVES: This paper aims to establish hospitalisation costs of mesothelioma in Italy and to evaluate hospital-related trends associated with the 1992 asbestos ban.

DESIGN: This is a retrospective population-based study of Italian hospitalisations treating pleura, peritoneum and pericardium mesothelioma in the period 2001-2018.

SETTINGS: Public and private Italian hospitals reached by the Ministry of Health (coverage close to 100%).

PARTICIPANTS: 157 221 admissions with primary or contributing diagnosis of pleural, peritoneal or hearth cancer discharged from 2001 to 2018.Primary and secondary outcome measures: number, length and cost of hospitalisations with related percentages.

RESULTS: Each year, Italian hospitals treated a mesothelioma in 6025 admissions on average. Mean annual costs by site were €20 293 733, €3183 632 and €40 443 for pleura, peritoneum and pericardium, respectively. Pericardial mesothelioma showed the highest cost per admission (€6117), followed by peritoneal (€4549) and pleural cases (€3809). Percentage of hospitalisation costs attributable to mesothelioma was higher when it is located in pleura (53.4%) and pericardium (51.8%) with respect to peritoneum (41.2%). Overall annual hospitalisation cost, percentages of number and length of admissions showed an inverted U-shape, with maxima (of €25 850 276, 0.064% and 0.096%, respectively) reached in 2011-2013. Mean age at discharge and percentages of surgery and of urgent cases increased over time.

CONCLUSIONS: The highest impact of mesothelioma on the National Health System was recorded 20 years after the asbestos ban (2011-2013). Hospitals should expect soon fewer but more severe patients needing more cares. To study the disease prevalence could help assistance planning of next decade.}, } @article {pmid34361048, year = {2021}, author = {Chmielewska-Kassassir, M and Wozniak, LA}, title = {Phytochemicals in Malignant Pleural Mesothelioma Treatment-Review on the Current Trends of Therapies.}, journal = {International journal of molecular sciences}, volume = {22}, number = {15}, pages = {}, pmid = {34361048}, issn = {1422-0067}, support = {2015/19/N/NZ3/01497//Narodowym Centrum Nauki/ ; }, mesh = {Animals ; Antineoplastic Agents, Phytogenic/chemistry/*therapeutic use ; Biological Products/chemistry/*therapeutic use ; Humans ; Mesothelioma, Malignant/*drug therapy/metabolism ; Polyphenols/chemistry/*therapeutic use ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare but highly aggressive tumor of pleura arising in response to asbestos fibers exposure. MPM is frequently diagnosed in the advanced stage of the disease and causes poor prognostic outcomes. From the clinical perspective, MPM is resistant to conventional treatment, thus challenging the therapeutic options. There is still demand for improvement and sensitization of MPM cells to therapy in light of intensive clinical studies on chemotherapeutic drugs, including immuno-modulatory and targeted therapies. One way is looking for natural sources, whole plants, and extracts whose ingredients, especially polyphenols, have potential anticancer properties. This comprehensive review summarizes the current studies on natural compounds and plant extracts in developing new treatment strategies for MPM.}, } @article {pmid34359365, year = {2021}, author = {Li, N and Yang, C and Zhou, S and Song, S and Jin, Y and Wang, D and Liu, J and Gao, Y and Yang, H and Mao, W and Chen, Z}, title = {Combination of Plasma-Based Metabolomics and Machine Learning Algorithm Provides a Novel Diagnostic Strategy for Malignant Mesothelioma.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {11}, number = {7}, pages = {}, pmid = {34359365}, issn = {2075-4418}, support = {81672315//National Natural Science Foundation of China/ ; 81302840//National Natural Science Foundation of China/ ; 2017C04G1360498//Key R&D Program Projects in Zhejiang Province/ ; LY20H280001//Zhejiang Provincial Natural Science Fund/ ; 2017KY256//Projects of Zhejiang Province Medical and Health Science and Technology Plan/ ; }, abstract = {BACKGROUND: Malignant mesothelioma (MM) is an aggressive and incurable carcinoma that is primarily caused by asbestos exposure. However, the current diagnostic tool for MM is still under-developed. Therefore, the aim of this study is to explore the diagnostic significance of a strategy that combined plasma-based metabolomics with machine learning algorithms for MM.

METHODS: Plasma samples collected from 25 MM patients and 32 healthy controls (HCs) were randomly divided into train set and test set, after which analyzation was performed by liquid chromatography-mass spectrometry-based metabolomics. Differential metabolites were screened out from the samples of the train set. Subsequently, metabolite-based diagnostic models, including receiver operating characteristic (ROC) curves and Random Forest model (RF), were established, and their prediction accuracies were calculated for the test set samples.

RESULTS: Twenty differential plasma metabolites were annotated in the train set; 10 of these metabolites were validated in the test set. The seven most prevalent diagnostic metabolites were taurocholic acid), 0.7142 (uracil), 0.7142 (biliverdin), 0.8571 (histidine), 0.5000 (tauroursodeoxycholic acid), 0.8571 (pyrroline hydroxycarboxylic acid), and 0.7857 (phenylalanine). Furthermore, RF based on 20 annotated metabolites showed a prediction accuracy of 0.9286, and its optimized version achieved 1.0000 in the test set. Moreover, the comparison between the samples of peritoneal MM (n = 8) and pleural MM (n = 17) illustrated a significant increase in levels of taurocholic acid and tauroursodeoxycholic acid, as well as an evident decrease in biliverdin.

CONCLUSIONS: Our results revealed the potential diagnostic value of plasma-based metabolomics combined with machine learning for MM. Further research with large sample size is worthy conducting. Moreover, our data demonstrated dysregulated metabolism pathways in MM, which aids in better understanding of molecular mechanisms related to the initiation and development of MM.}, } @article {pmid34354974, year = {2021}, author = {Visonà, SD and Capella, S and Bodini, S and Borrelli, P and Villani, S and Crespi, E and Colosio, C and Previderè, C and Belluso, E}, title = {Evaluation of Deposition and Clearance of Asbestos (Detected by SEM-EDS) in Lungs of Deceased Subjects Environmentally and/or Occupationally Exposed in Broni (Pavia, Northern Italy).}, journal = {Frontiers in public health}, volume = {9}, number = {}, pages = {678040}, pmid = {34354974}, issn = {2296-2565}, mesh = {*Asbestos/adverse effects ; Asbestos, Amphibole/adverse effects ; Asbestos, Serpentine/adverse effects ; Humans ; Lung ; *Lung Neoplasms/chemically induced ; }, abstract = {Biodurability is one of the main determinants of asbestos hazardousness for human health. Very little is known about the actual persistence of asbestos in lungs and its clearance, nor about differences in this regard between the different mineralogical types of asbestos. The aim of the present study was to evaluate the amount, the dimensional characteristics and the mineralogic kinds of asbestos in lungs (measured using SEM-EDS) of a series of 72 deceased subjects who were certainly exposed to asbestos (mainly crocidolite and chrysotile) during their life. Moreover, we investigated possible correlations between the lung burden of asbestos (in general and considering each asbestos type), as well as their dimension (length, width, and l/w ratio) and the duration of exposure, the latency- in case of malignant mesothelioma (MM), the survival and the time since the end of exposure. In 62.5% of subjects, asbestos burden in lungs was lower that the threshold considered demonstrative for occupational exposure. In 29.1% of cases no asbestos was found. Chrysotile was practically not detected. The mean length of asbestos fibers and the length to width ratio were significantly related to the duration of exposure to asbestos. No other statistically significant correlations were found between the amount and dimensional characteristics of asbestos (nor with the relative amount of each asbestos type) and the other chronological variables considered. In conclusion, it was pointed out that chrysotile can be completely removed from human lungs in <8 years and, instead, amphiboles persist much more time. The present results suggest, as well, that the finding of no asbestos in lungs cannot rule out the attribution of MM to asbestos (in particular, chrysotile) inhaled in an occupational setting. This point is of crucial importance from a legal point of view.}, } @article {pmid34350658, year = {2021}, author = {Mensi, C and Zellino, C and Polonioli, M and Dallari, B and Pesatori, AC and Riboldi, L and Consonni, D}, title = {Pleural mesothelioma in a circus worker.}, journal = {Journal of occupational health}, volume = {63}, number = {1}, pages = {e12250}, pmid = {34350658}, issn = {1348-9585}, support = {acronym: PRIMATE-code ARL_2/2018//Fondazione Regionale per la Ricerca Biomedica/ ; BRiC P55 and//Istituto Nazionale per l'Assicurazione Contro Gli Infortuni sul Lavoro/ ; BRiC P59//Istituto Nazionale per l'Assicurazione Contro Gli Infortuni sul Lavoro/ ; }, mesh = {Aged, 80 and over ; Asbestos/*toxicity ; Humans ; Italy ; Male ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; Occupational Exposure/*adverse effects ; }, abstract = {OBJECTIVES: To describe an unusual occupational asbestos exposure in a patient with mesothelioma.

METHODS: Since 2000, the Lombardy Mesothelioma Registry (LMR) collects cases of malignant mesothelioma (MM) occurring among people residing in the Lombardy Region, North-West Italy, with a population of 10 million inhabitants. For each case, clinical records and asbestos exposure are collected. Each case is then classified in agreement with the guidelines of the National Mesothelioma Registry.

RESULTS: We identified a male (86 years old), former smoker, who had been working for 53 years as a circus truck driver and tamer of lions and tigers. The first circumstance of exposure was the use of an asbestos tape that wrapped around the hoop in the feline jumping show with a flaming hoop. The second one was the presence of insulating panels protecting the engine placed inside the trucks.

CONCLUSION: A new MM case with an occupational etiology has been found in the public entertainment, an occupational sector not usually considered at risk for the presence of asbestos.}, } @article {pmid34349988, year = {2021}, author = {Iyoda, A and Azuma, Y and Sakai, T and Koezuka, S and Otsuka, H and Tochigi, N and Isobe, K and Sano, A}, title = {Intraoperative argon-plasma coagulation treatment for patients with malignant pleural mesothelioma.}, journal = {Molecular and clinical oncology}, volume = {15}, number = {3}, pages = {188}, pmid = {34349988}, issn = {2049-9469}, abstract = {Malignant pleural mesothelioma (MPM) is often associated with asbestos exposure and carries an extremely poor prognosis. The present study assessed the effectiveness of argon plasma coagulation (APC) treatment in patients with MPM who underwent radical pleural decortication (PD). The clinical data from 11 patients who underwent radical PD treated with APC at Toho University Omori Medical Center from July 2015 to March 2020 were retrospectively analyzed. Clinical features, local recurrence, and clinical prognoses were evaluated. The median overall survival was 18.5 months, and the 1- and 2-year overall survival rates were 71.6 and 43.0%, respectively. One patient survived 5 years but had recurrent tumors. The median disease-free survival was 11.1 months. The 1- and 2-year disease-free survival rates were 49.9 and 12.5%, respectively. Three patients had no recurrences, two of whom were followed continuously (39.6 and 10.2 months). The present study revealed that APC treatment for MPM might be associated with good survival and prognosis. APC as an additional intraoperative treatment for patients with MPM may be further investigated with larger multi-center clinical trials to support its efficacy.}, } @article {pmid34345849, year = {2021}, author = {Gualtieri, AF}, title = {Bridging the gap between toxicity and carcinogenicity of mineral fibres by connecting the fibre crystal-chemical and physical parameters to the key characteristics of cancer.}, journal = {Current research in toxicology}, volume = {2}, number = {}, pages = {42-52}, pmid = {34345849}, issn = {2666-027X}, abstract = {Airborne fibres and particularly asbestos represent hazards of great concern for human health because exposure to these peculiar particulates may cause malignancies such as lung cancer and mesothelioma. Currently, many researchers worldwide are focussed on fully understanding the patho-biological mechanisms leading to carcinogenesis prompted by pathogenic fibres. Along this line, the present work introduces a novel approach to correlate how and to what extent the physical/crystal-chemical and morphological parameters (including length, chemistry, biodurability, and surface properties) of mineral fibres cause major adverse effects with an emphasis on asbestos. The model described below conceptually attempts to bridge the gap between toxicity and carcinogenicity of mineral fibres and has several implications: 1) it provides a tool to measure the toxicity and pathogenic potential of asbestos minerals, allowing a quantitative rank of the different types (e.g. chrysotile vs. crocidolite); 2) it can predict the toxicity and pathogenicity of "unregulated" or unclassified fibres; 3) it reveals the parameters of a mineral fibre that are active in stimulating key characteristics of cancer, thus offering a strategy for developing specific cancer prevention strategies and therapies. Chrysotile, crocidolite and fibrous glaucophane are described here as mineral fibres of interest.}, } @article {pmid34339095, year = {2021}, author = {Prusak, A and van der Zwan, JM and Aarts, MJ and Arber, A and Cornelissen, R and Burgers, S and Duijts, SFA}, title = {The psychosocial impact of living with mesothelioma: Experiences and needs of patients and their carers regarding supportive care.}, journal = {European journal of cancer care}, volume = {30}, number = {6}, pages = {e13498}, doi = {10.1111/ecc.13498}, pmid = {34339095}, issn = {1365-2354}, mesh = {Adaptation, Psychological ; Aged ; Caregivers ; Female ; Humans ; Male ; *Mesothelioma/therapy ; *Mesothelioma, Malignant ; Qualitative Research ; }, abstract = {OBJECTIVE: Mesothelioma is a rare cancer with a poor prognosis caused by exposure to asbestos. Psychosocial support and care for mesothelioma patients and their carers is limited and not tailored to their specific needs. The aim of this study was to explore patients' and carers' needs and experiences regarding psychosocial support and their coping mechanisms dealing with psychosocial problems.

METHODS: A qualitative study was performed using semi-structured interviews with both mesothelioma patients and their carers. Participants were recruited through two specialised hospitals and two patient organisations. All interviews were transcribed verbatim and thematically analysed.

RESULTS: Ten patients (70% male, mean age 67.7) and five carers (20% male, mean age 65) participated in the study. The main themes identified for patients were active coping, limited needs and limited knowledge and awareness about psychosocial support. The main themes for carers were passive coping and 'it's all about the patient'.

CONCLUSION: Mesothelioma patients do not seem to have high needs for psychosocial support, whereas carers do. However, knowledge about and awareness of psychosocial support is low among mesothelioma patients. The findings from this study should be used to adjust guidelines for psychosocial support in mesothelioma patients and their carers.}, } @article {pmid34333253, year = {2021}, author = {Onagi, H and Hayashi, T and Saito, T and Kishikawa, S and Takamochi, K and Suzuki, K}, title = {Malignant pleural mesothelioma showing rare morphology indistinguishable from myxofibrosarcoma concomitant with EGFR-mutated lung adenocarcinoma: A case report.}, journal = {International journal of surgery case reports}, volume = {85}, number = {}, pages = {106237}, pmid = {34333253}, issn = {2210-2612}, abstract = {INTRODUCTION AND IMPORTANCE: Primary tumors of the pleura are rare, with malignant mesothelioma being the most common of these neoplasms. Pathological diagnosis of sarcomatoid mesothelioma can be more challenging than that of epithelioid malignant mesothelioma because of its similarities with true sarcomas and restricted or inconsistent expression of mesothelial markers in immunohistochemistry analysis.

PRESENTATION OF CASE: Here, we present an unusual case of malignant pleural mesothelioma concomitant with lung adenocarcinoma in a 72-year-old Japanese man, a smoker with no family history of cancer and asbestos exposure. Malignant pleural mesothelioma is composed of epithelial and spindle-shaped cells. Spindle-shaped cells with scant eosinophilic cytoplasm and hyperchromatic nuclei proliferated in abundant myxoid stroma containing thin-walled blood vessels, mimicking myxofibrosarcoma. The loss of BAP1 (BRCA1-associated protein 1) expression, as assessed by immunohistochemistry, and homozygous deletions of CDKN2A, detected using fluorescence in situ hybridization (FISH), were observed in both components. Targeted sequencing revealed that lung adenocarcinoma harbored EGFR mutations, whereas no mutations were detected in either component of biphasic mesothelioma.

DISCUSSION: Although alcian blue-stained mucins were detected in biphasic mesothelioma subsets, the clinicopathological significance of myxoid stroma in biphasic and sarcomatoid mesothelioma remains largely unknown.

CONCLUSION: Our case presented a unique morphology mimicking myxofibrosarcoma in a sarcomatoid component of biphasic mesothelioma; therefore, it raises a question on the clinicopathological significance of myxoid stroma in sarcomatous areas of biphasic and sarcomatoid mesothelioma.}, } @article {pmid34322630, year = {2021}, author = {Scopa, P}, title = {Reconstruction of asbestos exposure in workers suffering from pleural neoplasms and employed in sectors not generally associated with high exposure levels: the importance of an accurate standardized assessment of occupational medicine.}, journal = {Journal of preventive medicine and hygiene}, volume = {62}, number = {1}, pages = {E148-E151}, pmid = {34322630}, issn = {2421-4248}, mesh = {*Asbestos/adverse effects ; Humans ; *Mesothelioma/diagnosis/etiology ; *Occupational Exposure/adverse effects/analysis ; *Occupational Medicine ; *Pleural Neoplasms/diagnosis/etiology ; Reproducibility of Results ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma onset in workers exposed to asbestos is well known with reference to multiple working sectors. In some cases, occurring among workers of sectors characterized by a presumed lower relevance of asbestos exposure, the absence of a well-defined correlation can prevent their emergence and compensation. To improve definition of these cases, this article underlines the importance of a standardized approach to occupational anamnesis.

METHODS: Thorough standardized occupational health assessment method application in a case of pleural malignant neoplasm occurred in a hauler, a job generally not associated with high levels of exposure to asbestos fibres.

RESULTS: Assessment of malignant pleural mesothelioma diagnosis and dual mode relevant occupational exposure to asbestos during both truck driving and loading and unloading operations of asbestos-containing goods.

CONCLUSIONS: Systematic occupational medicine assessment with accurate standardized approach is essential for reconstruction of asbestos exposure, in order to highlight every aspect useful to establish causal link between cases of pleural mesothelioma and possible occupational and non-occupational exposure to the mineral, even in cases where the first-level occupational history does not appear to be suggestive.}, } @article {pmid34313510, year = {2021}, author = {Brustugun, OT and Nilssen, Y and Eide, IJZ}, title = {Epidemiology and outcome of peritoneal and pleural mesothelioma subtypes in Norway. A 20 year nation-wide study.}, journal = {Acta oncologica (Stockholm, Sweden)}, volume = {60}, number = {10}, pages = {1250-1256}, doi = {10.1080/0284186X.2021.1955971}, pmid = {34313510}, issn = {1651-226X}, mesh = {Female ; Humans ; Male ; *Mesothelioma/epidemiology/therapy ; *Mesothelioma, Malignant ; *Peritoneal Neoplasms/epidemiology/therapy ; *Pleural Neoplasms/epidemiology/therapy ; Prognosis ; }, abstract = {BACKGROUND: Mesothelioma of the pleural or peritoneal cavities is one of the deadliest cancer types. The incidence of pleural subtypes has decreased over time due to decrease in asbestos exposure, and the current treatment landscape is changing due to introduction of novel therapies. In this study we have analysed contemporary epidemiological data of mesothelioma on a national level before the advent of immunotherapy.

MATERIAL AND METHODS: Complete national data on 1509 pleural and peritoneal malignant mesothelioma from the Cancer Registry of Norway from 2000 to 2019 are presented. Age standardised incidence and median survival were calculated.

RESULTS: The age-standardised incidence of pleural mesothelioma among males has decreased from 1.7 per 100 000 in 2000-2004 to 1.1 in 2015-2019, whereas the incidence for females has been stable, lower than 0.3 per 100 000 throughout the period. Incidence of peritoneal mesotheliomas remained low, below 0.08 per 100 000. The female to male ratio among pleural mesotheliomas was 1:7 with no differences among morphological subtypes, whereas this ratio was 1:1.2 in peritoneal mesotheliomas. Median age at diagnosis for pleural mesothelioma was 73 years and 76 years for females and males respectively in the last 5-year period, and 67 years for peritoneal mesotheliomas of both sexes. Median survival among pleural mesotheliomas has been stable, with significantly worse prognosis among sarcomatoid subtype (5.4 months) compared to epithelioid subtype (15.8 months). Peritoneal mesothelioma of the epithelioid subtype, representing 38% of cases, had a median survival of 43.3 months, contrasting the non-epithelioid subtype of 5.1 months.

DISCUSSION: Mesothelioma is still a significant disease with a dismal prognosis. Improvement in treatment is warranted.}, } @article {pmid34299971, year = {2021}, author = {Fang, YJ and Chuang, HY and Pan, CH and Chang, YY and Cheng, Y and Lee, LJ and Wang, JD}, title = {Increased Risk of Gastric Cancer in Asbestos-Exposed Workers: A Retrospective Cohort Study Based on Taiwan Cancer Registry 1980-2015.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {14}, pages = {}, pmid = {34299971}, issn = {1660-4601}, mesh = {*Asbestos/toxicity ; Cohort Studies ; Female ; Humans ; Incidence ; *Lung Neoplasms ; Male ; *Mesothelioma ; *Occupational Diseases/chemically induced/epidemiology ; *Occupational Exposure/adverse effects ; Registries ; Retrospective Studies ; *Stomach Neoplasms/chemically induced/epidemiology ; Taiwan/epidemiology ; }, abstract = {Asbestos has been recognized as a human carcinogen associated with malignant mesothelioma, cancers of lung, larynx, and ovary. However, a putative association between gastric cancer and asbestos exposure remains controversial. In this study, we aimed to explore gastric cancer risk of workers potentially exposed to asbestos in Taiwan. The asbestos occupational cohort was established from 1950 to 2015 based on the Taiwan Labor Insurance Database, and Taiwan Environmental Protection Agency regulatory datasets, followed by the Taiwan Cancer Registry for the period 1980-2015. Standardized incidence ratios (SIRs) for cancer were computed for the whole cohort using reference rates of the general population, and also reference labor population. Compared with the general population, SIR of the asbestos occupational cohort for the gastric cancer increased both in males (1.05, 95% confidence interval (CI): 1.02-1.09) and females (1.10, 95% CI: 1.01-1.18). A total of 123 worksites were identified to have cases of malignant mesothelioma, where increased risk for gastric cancer was found with a relative risk of 1.76 (95% CI: 1.63-1.90). This 35-year retrospective cohort study of asbestos-exposed workers in Taiwan may provide support for an association between occupational exposure to asbestos and gastric cancer.}, } @article {pmid34299035, year = {2021}, author = {Yuan, L and Sun, B and Xu, L and Chen, L and Ou, W}, title = {The Updating of Biological Functions of Methyltransferase SETDB1 and Its Relevance in Lung Cancer and Mesothelioma.}, journal = {International journal of molecular sciences}, volume = {22}, number = {14}, pages = {}, pmid = {34299035}, issn = {1422-0067}, support = {2020Y002//the Fundamental Research Funds of Zhejiang Sci-Tech University/ ; 81728012//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Histone-Lysine N-Methyltransferase/*metabolism ; Humans ; Lung Neoplasms/metabolism/*pathology ; Mesothelioma/metabolism/*pathology ; }, abstract = {SET domain bifurcated 1 (SETDB1) is a histone H3 lysine 9 (H3K9) methyltransferase that exerts important effects on epigenetic gene regulation. SETDB1 complexes (SETDB1-KRAB-KAP1, SETDB1-DNMT3A, SETDB1-PML, SETDB1-ATF7IP-MBD1) play crucial roles in the processes of histone methylation, transcriptional suppression and chromatin remodelling. Therefore, aberrant trimethylation at H3K9 due to amplification, mutation or deletion of SETDB1 may lead to transcriptional repression of various tumour-suppressing genes and other related genes in cancer cells. Lung cancer is the most common type of cancer worldwide in which SETDB1 amplification and H3K9 hypermethylation have been indicated as potential tumourigenesis markers. In contrast, frequent inactivation mutations of SETDB1 have been revealed in mesothelioma, an asbestos-associated, locally aggressive, highly lethal, and notoriously chemotherapy-resistant cancer. Above all, the different statuses of SETDB1 indicate that it may have different biological functions and be a potential diagnostic biomarker and therapeutic target in lung cancer and mesothelioma.}, } @article {pmid34298661, year = {2021}, author = {Pouliquen, DL and Kopecka, J}, title = {Malignant Mesothelioma.}, journal = {Cancers}, volume = {13}, number = {14}, pages = {}, pmid = {34298661}, issn = {2072-6694}, abstract = {Malignant mesothelioma (MM) is a rare and aggressive cancer, related to chronic inflammation and oxidative stress caused mainly by exposure to asbestos [...].}, } @article {pmid34295692, year = {2021}, author = {Menis, J and Pasello, G and Remon, J}, title = {Immunotherapy in malignant pleural mesothelioma: a review of literature data.}, journal = {Translational lung cancer research}, volume = {10}, number = {6}, pages = {2988-3000}, pmid = {34295692}, issn = {2218-6751}, abstract = {Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer of the pleural surface, associated with asbestos exposure, whose incidence is still growing in some areas of the world. MPM is still considered a rare and an orphan disease with an unchanged median overall survival (OS) ranging from 8 to 14 months and no treatment advances in the last 15 years both in local and advanced disease. In the recent years, chronic inflammation of the mesothelium together with local tumor suppression plays a major role in the malignant transformation. Also, significant heterogeneity in both tumor and the microenvironment is at the basis of MPM biology. Preclinical data have demonstrated the immunogenicity and the lack of an effective antitumor response by the immune system in MPM thus paving the way to the development of immune therapeutics in this disease. Still there is no clear evidence of any predictive biomarker so that, given the close interaction between the immune infiltrate and mesothelial cells, a number of trials are ongoing to investigate the role and prognostic value of the immune microenvironment. In this review we summarize the rationale for immune therapeutics development in MPM, as well as, the relevant literature and ongoing trials of immune checkpoint inhibitors (ICIs) and vaccines used as both first-line treatment and beyond.}, } @article {pmid34295165, year = {2021}, author = {Gu, R and Jiang, L and Duan, T and Chen, C and Wu, S and Mu, D}, title = {A Case of Pulmonary Embolism with Sarcomatoid Malignant Pleural Mesothelioma with Long-Term Pleural Effusion.}, journal = {OncoTargets and therapy}, volume = {14}, number = {}, pages = {4231-4237}, pmid = {34295165}, issn = {1178-6930}, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a highly aggressive tumor that originates from pleural mesothelial cells. In recent years, with the development of asbestos-related industries and the increase in air pollution, its incidence has been increased. The incidence of pulmonary embolism combined with sarcomatoid MPM is very low and the prognosis is extremely poor. We here report a case of a patient with long term of pleural effusion and finally diagnosed as pulmonary embolism with sarcomatoid MPM.

CASE: A 75-year-old male with a 30-year history of asbestos exposure was admitted to our hospital due to chest pain and difficulty in breathing after exercise. Radiologic examination revealed pleural effusion, computed tomography pulmonary angiography (CTPA) suggests pulmonary embolism, and we consider pleural effusion caused by pulmonary embolism. After anticoagulant therapy for pulmonary embolism and pleural puncture to reduce pleural effusion, the patient's symptoms improved. However, after that, the patient was still admitted to the hospital several times because of recurrent chest pain and dyspnea symptoms, and radiologic examination always showed unexplained pleural effusion. Finally, pathological and immunohistochemical examinations of the pleural biopsy specimens were performed, and the diagnosis was confirmed as sarcomatoid MPM.

CONCLUSION: In summary, sarcomatoid MPM with pulmonary embolism is relatively rare, and the prognosis is poor. Clinicians need to be alert to its occurrence. When the first diagnosis is confirmed and the effect of targeted treatment is still not good, the possibility of other diseases should be considered. In clinical practice, pleural biopsy guided by PET-CT is a good choice for patients with sarcomatoid MPM who cannot tolerate open pleural biopsies or thoracoscopy. And patients should undergo pleural morphology and immunohistochemistry as soon as possible, which are helpful for timely diagnosis.}, } @article {pmid34291807, year = {2021}, author = {Santana, VS and Salvi, L and Cavalcante, F and Campos, F and Algranti, E}, title = {Underreporting of mesothelioma, asbestosis and pleural plaques in Brazil.}, journal = {Occupational medicine (Oxford, England)}, volume = {71}, number = {4-5}, pages = {223-230}, doi = {10.1093/occmed/kqab073}, pmid = {34291807}, issn = {1471-8405}, mesh = {*Asbestos/adverse effects ; *Asbestosis ; Brazil/epidemiology ; Humans ; *Lung Neoplasms ; *Mesothelioma/etiology ; *Pleural Diseases/etiology ; *Pleural Neoplasms/etiology ; }, abstract = {BACKGROUND: Brazil has a long history of heavy asbestos consumption. However, the number of asbestos-related diseases (ARDs) falls far below the one expected compared with other asbestos consumer countries.

AIMS: To examine underreporting of ARDs, that is mesothelioma, asbestosis and pleural plaques, in Brazil's Mortality Information System (SIM).

METHODS: Health information systems (HIS) were mapped, datasets retrieved and records of ARD deaths extracted. Records were pair-matched using anonymous linkage to create a single database. ARD-reported cases missing in SIM were considered unreported. The study's period ranged from 2008 to 2014, when every HIS contributed to the ARD records pool.

RESULTS: A total of 1298 registered ARD deaths were found, 996 cases of mesothelioma (77%) and 302 (23%) of asbestosis and pleural plaques. SIM was the major single data source of ARD but 335 mesothelioma deaths were missing, an average underreporting of 33%, with no clear time trend. For asbestosis and pleural plaques, underreporting of ARD oscillated from 55% in 2010 to 25% in 2014, a declining trend. ARD underreporting was not associated with sex or age.

CONCLUSIONS: One-third of underreported ARD deaths in the universal SIM is unacceptably high and, apparently, it has not been improving substantially over time. After recoveries from multiple databases, the number of cases is still below, which could be expected based on asbestos consumption. Interoperability of multiple information systems could enhance case detection and improve the precision of mortality estimates, which are crucial for surveillance and for evaluation of remedial policies.}, } @article {pmid34283067, year = {2021}, author = {Oddone, E and Bollon, J and Nava, CR and Consonni, D and Marinaccio, A and Magnani, C and Gasparrini, A and Barone-Adesi, F}, title = {Effect of Asbestos Consumption on Malignant Pleural Mesothelioma in Italy: Forecasts of Mortality up to 2040.}, journal = {Cancers}, volume = {13}, number = {13}, pages = {}, pmid = {34283067}, issn = {2072-6694}, support = {MR/R013349/1/MRC_/Medical Research Council/United Kingdom ; }, abstract = {Statistical models used to forecast malignant pleural mesothelioma (MPM) trends often do not take into account historical asbestos consumption, possibly resulting in less accurate predictions of the future MPM death toll. We used the distributed lag non-linear model (DLNM) approach to predict future MPM cases in Italy until 2040, based on past asbestos consumption figures. Analyses were conducted using data on male MPM deaths (1970-2014) and annual asbestos consumption using data on domestic production, importation, and exportation. According to our model, the peak of MPM deaths is expected to occur in 2021 (1122 expected cases), with a subsequent decrease in mortality (344 MPM deaths in 2039). The exposure-response curve shows that relative risk (RR) of MPM increased almost linearly for lower levels of exposure but flattened at higher levels. The lag-specific RR grew until 30 years since exposure and decreased thereafter, suggesting that the most relevant contributions to the risk come from exposures which occurred 20-40 years before death. Our results show that the Italian MPM epidemic is approaching its peak and underline that the association between temporal trends of MPM and time since exposure to asbestos is not monotonic, suggesting a lesser role of remote exposures in the development of MPM than previously assumed.}, } @article {pmid34281119, year = {2021}, author = {Visonà, SD and Capella, S and Bodini, S and Borrelli, P and Villani, S and Crespi, E and Frontini, A and Colosio, C and Vigliaturo, R and Belluso, E}, title = {Reply to Mirabelli et al. Is Mesothelioma Unrelated to the Lung Asbestos Burden? Comment on "Visonà et al. Inorganic Fiber Lung Burden in Subjects with Occupational and/or Anthropogenic Environmental Asbestos Exposure in Broni (Pavia, Northern Italy): An SEM-EDS Study on Autoptic Samples. Int. J. Environ. Res. Public Health 2021, 18, 2053".}, journal = {International journal of environmental research and public health}, volume = {18}, number = {13}, pages = {}, pmid = {34281119}, issn = {1660-4601}, mesh = {*Asbestos/toxicity ; Humans ; Italy/epidemiology ; Lung ; *Mesothelioma/chemically induced/epidemiology ; *Occupational Exposure/adverse effects ; Public Health ; }, abstract = {We appreciate very much the interest of Mirabelli et al. [...].}, } @article {pmid34281114, year = {2021}, author = {Mirabelli, D and Angelini, A and Barbieri, PG and Calisti, R and Capacci, F and Girardi, P and Silvestri, S and Somigliana, AB}, title = {Is Mesothelioma Unrelated to the Lung Asbestos Burden? Comment on Visonà et al. Inorganic Fiber Lung Burden in Subjects with Occupational and/or Anthropogenic Environmental Asbestos Exposure in Broni (Pavia, Northern Italy): An SEM-EDS Study on Autoptic Samples. Int. J. Environ. Res. Public Health 2021, 18, 2053.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {13}, pages = {}, pmid = {34281114}, issn = {1660-4601}, mesh = {*Asbestos/toxicity ; Humans ; Italy/epidemiology ; Lung ; *Lung Neoplasms/epidemiology ; *Mesothelioma/epidemiology ; Public Health ; }, abstract = {We read with interest the report by Visonà and coworkers on the lung asbestos fiber burden in an autopsy series of decedents from mesothelioma (MM: 59 cases) and individuals who "suffered from asbestosis and died of its complications" (13 cases) [...].}, } @article {pmid34277071, year = {2021}, author = {Freudenberger, DC and Shah, RD}, title = {A narrative review of the health disparities associated with malignant pleural mesothelioma.}, journal = {Journal of thoracic disease}, volume = {13}, number = {6}, pages = {3809-3815}, pmid = {34277071}, issn = {2072-1439}, abstract = {Malignant pleural mesothelioma (MPM) is a cancer of the mesothelial lining of the pleura that has traditionally been associated with asbestos exposure in an industrial setting. Asbestos usage has fortunately been banned or phased out in most industrialized countries resulting in its decline in countries such as the United States. Despite this, MPM continues to place significant burden on its affected patients resulting in overall poor prognosis and survival. Questions arise as to what factors, especially what health disparities, contribute to the disease's dismal prognosis. This article will present a narrative review of recent literature that identifies the impact age, sex, race, access to medical centers, and economics have on the diagnosis, treatment, and prognosis of MPM. As will be discussed, research has shown that factors including younger age, female sex, non-white race, private insurance, Medicare, and higher income have been associated with better survival in MPM. Whereas older age, male sex, white race, lack of insurance, and lower income are associated with worse survival. The identification of these and other health disparities related to MPM may allow for future research, clinical guidelines, and policies to be implemented to decrease the burden health disparities create in the diagnosis, treatment, and prognosis of patients with MPM.}, } @article {pmid34249695, year = {2021}, author = {Hiltbrunner, S and Mannarino, L and Kirschner, MB and Opitz, I and Rigutto, A and Laure, A and Lia, M and Nozza, P and Maconi, A and Marchini, S and D'Incalci, M and Curioni-Fontecedro, A and Grosso, F}, title = {Tumor Immune Microenvironment and Genetic Alterations in Mesothelioma.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {660039}, pmid = {34249695}, issn = {2234-943X}, abstract = {Malignant pleural mesothelioma (MPM) is a rare and fatal disease of the pleural lining. Up to 80% of the MPM cases are linked to asbestos exposure. Even though its use has been banned in the industrialized countries, the cases continue to increase. MPM is a lethal cancer, with very little survival improvements in the last years, mirroring very limited therapeutic advances. Platinum-based chemotherapy in combination with pemetrexed and surgery are the standard of care, but prognosis is still unacceptably poor with median overall survival of approximately 12 months. The genomic landscape of MPM has been widely characterized showing a low mutational burden and the impairment of tumor suppressor genes. Among them, BAP1 and BLM are present as a germline inactivation in a small subset of patients and increases predisposition to tumorigenesis. Other studies have demonstrated a high frequency of mutations in DNA repair genes. Many therapy approaches targeting these alterations have emerged and are under evaluation in the clinic. High-throughput technologies have allowed the detection of more complex molecular events, like chromotripsis and revealed different transcriptional programs for each histological subtype. Transcriptional analysis has also paved the way to the study of tumor-infiltrating cells, thus shedding lights on the crosstalk between tumor cells and the microenvironment. The tumor microenvironment of MPM is indeed crucial for the pathogenesis and outcome of this disease; it is characterized by an inflammatory response to asbestos exposure, involving a variety of chemokines and suppressive immune cells such as M2-like macrophages and regulatory T cells. Another important feature of MPM is the dysregulation of microRNA expression, being frequently linked to cancer development and drug resistance. This review will give a detailed overview of all the above mentioned features of MPM in order to improve the understanding of this disease and the development of new therapeutic strategies.}, } @article {pmid34244457, year = {2022}, author = {Thomsen, RW and Riis, AH and Flachs, EM and Garabrant, DH and Bonde, JPE and Sørensen, HT}, title = {Risk of asbestosis, mesothelioma, other lung disease or death among motor vehicle mechanics: a 45-year Danish cohort study.}, journal = {Thorax}, volume = {77}, number = {5}, pages = {477-485}, doi = {10.1136/thoraxjnl-2020-215041}, pmid = {34244457}, issn = {1468-3296}, mesh = {Adult ; *Asbestos/adverse effects/analysis ; *Asbestosis/epidemiology ; Cohort Studies ; Denmark/epidemiology ; Humans ; *Lung Neoplasms/epidemiology/etiology ; Male ; *Mesothelioma/epidemiology/etiology ; *Mesothelioma, Malignant ; Motor Vehicles ; *Occupational Diseases/epidemiology/etiology ; *Occupational Exposure/adverse effects ; *Pleural Neoplasms/complications ; Young Adult ; }, abstract = {INTRODUCTION: The risk of asbestosis, malignant mesothelioma and lung cancer among motor vehicle mechanics is of concern because of potential exposure to chrysotile asbestos during brake, clutch and gasket repair and maintenance. Asbestos has also been used in insulation and exhaust systems.

METHODS: We examined the long-term risk of incident mesothelioma, lung cancer, asbestosis and other lung diseases and mortality due to mesothelioma, lung cancer, asbestosis and other lung diseases in a nationwide cohort of all men registered as motor vehicle mechanics since 1970 in Denmark. This was compared with the corresponding risk in a cohort of male workers matched 10:1 by age and calendar year, with similar socioeconomic status (instrument makers, dairymen, upholsterers, glaziers, butchers, bakers, drivers, farmers and workers in the food industry, trade or public services).

RESULTS: Our study included 138 559 motor vehicle mechanics (median age 24 years; median follow-up 20 years (maximum 45 years)) and 1 385 590 comparison workers (median age 25 years; median follow-up 19 years (maximum 45 years)). Compared with other workers, vehicle mechanics had a lower risk of morbidity due to mesothelioma/pleural cancer (n=47 cases) (age-adjusted and calendar-year-adjusted HR=0.74 (95% CI 0.55 to 0.99)), a slightly increased risk of lung cancer (HR=1.09 (95% CI 1.03 to 1.14)), increased risk of asbestosis (HR=1.50 (95% CI 1.10 to 2.03)) and a chronic obstructive pulmonary disease risk close to unity (HR=1.02 (95% CI 0.99 to 1.05)). Corresponding HRs for mortality were 0.86 (95% CI 0.64 to 1.15) for mesothelioma/pleural cancer, 1.06 (95% CI 1.01 to 1.12) for lung cancer, 1.79 (95% CI 1.10 to 2.92) for asbestosis, 1.06 (95% CI 0.86 to 1.30) for other lung diseases caused by external agents and 1.00 (95% CI 0.98 to 1.01) for death due to all causes.

CONCLUSIONS: We found that the risk of asbestosis was increased among vehicle mechanics. The risk of malignant mesothelioma/pleural cancers was not increased among vehicle mechanics.}, } @article {pmid34241641, year = {2021}, author = {Golka, K and Böthig, R and Jungmann, O and Forchert, M and Zellner, ME and Schöps, W}, title = {[Occupational cancers in urology].}, journal = {Der Urologe. Ausg. A}, volume = {60}, number = {8}, pages = {1061-1072}, pmid = {34241641}, issn = {1433-0563}, mesh = {Humans ; *Kidney Neoplasms ; Male ; *Occupational Diseases/diagnosis/epidemiology/etiology ; *Occupational Exposure/adverse effects ; *Urinary Bladder Neoplasms/chemically induced/epidemiology ; *Urology ; }, abstract = {Cancers can be triggered by occupational causes. In the field of urology, bladder cancer is by far the most frequent occupationally induced tumor disease. Causes are particularly carcinogenic aromatic amines and carcinogenic polycyclic aromatic hydrocarbons. The frequency of this disease has shifted over the last decades from the classical hazard in the chemical industry to the users. Among a variety of hazardous occupations, hairdressers and painters are the best known. Rarely, renal cell carcinoma can be triggered by high trichloroethylene exposure and mesothelioma of the tunica vaginalis testis by asbestos. If a disease that can be caused by occupational activities has been confirmed (e.g. urinary bladder cancer), the risk factors must be recorded by a complete occupational history from the first employment on in order to be able to report a suspected occupational disease. In addition, spinal cord injury due to occupational and commuting accidents can lead to urinary bladder cancer over the long term.}, } @article {pmid34240508, year = {2021}, author = {Hiroshima, K and Wu, D and Koh, E and Sekine, Y and Ozaki, D and Yusa, T and Nakazawa, T and Tsuji, S and Miyagi, Y and Walts, AE and Marchevsky, AM and Husain, AN and Imai, K}, title = {Membranous HEG1 expression is a useful marker in the differential diagnosis of epithelioid and biphasic malignant mesothelioma versus carcinomas.}, journal = {Pathology international}, volume = {71}, number = {9}, pages = {604-613}, pmid = {34240508}, issn = {1440-1827}, support = {//Ministry of the Environment of Japan/ ; JP20cm0106406//Japan Agency for Medical Research and Development/ ; //Nichias Corporation, Tokyo, Japan/ ; }, mesh = {Carcinoma, Squamous Cell/*diagnosis/pathology ; Diagnosis, Differential ; Epithelium/pathology ; Humans ; Immunohistochemistry ; Lung Neoplasms/*diagnosis/pathology ; Membrane Proteins/genetics/*metabolism ; Mesothelioma, Malignant/*diagnosis/pathology ; Tissue Array Analysis ; }, abstract = {Sialylated HEG1 has been reported as a highly specific and sensitive mesothelioma marker but a comprehensive evaluation of its expression in carcinomas in different organs, various sarcomas and reactive mesothelial proliferations has not been reported. The aim of this study was to evaluate the clinical applicability of HEG1 as a marker in the diagnosis of mesothelioma. HEG1 immunoreactivity was evaluated in whole sections of 122 mesotheliomas, 75 pulmonary carcinomas, 55 other carcinomas, 16 mesenchymal tumors, and 24 reactive mesothelial proliferations and in tissue microarrays containing 70 epithelioid (EM), 36 biphasic (BM), and 2 sarcomatoid mesotheliomas (SM). In whole sections and tissue microarrays, respectively, membranous HEG1 was expressed in 93.0% and 85.5% of EM, 81.3% and 69.4% of BM, 0% and 0% of SM. HEG1 was not expressed in pulmonary adenocarcinomas. HEG1 was expressed as cytoplasmic immunoreactivity in pulmonary squamous cell carcinomas (21.7%). Membranous HEG1 staining was seen in ovarian carcinomas (66.7%), thyroid carcinomas (100%), reactive conditions (16.7%), and mesenchymal tumors (18.8%). The sensitivity of membranous HEG1 expression to distinguish EM/BM from all carcinomas was 88.8%. The specificity for the differential diagnosis between EM/BM and all carcinomas and pulmonary carcinomas was 92.3% and 98.7%, respectively.}, } @article {pmid34235080, year = {2021}, author = {Behrouzfar, K and Burton, K and Mutsaers, SE and Morahan, G and Lake, RA and Fisher, SA}, title = {How to Better Understand the Influence of Host Genetics on Developing an Effective Immune Response to Thoracic Cancers.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {679609}, pmid = {34235080}, issn = {2234-943X}, abstract = {Thoracic cancers pose a significant global health burden. Immune checkpoint blockade therapies have improved treatment outcomes, but durable responses remain limited. Understanding how the host immune system interacts with a developing tumor is essential for the rational development of improved treatments for thoracic malignancies. Recent technical advances have improved our understanding of the mutational burden of cancer cells and changes in cancer-specific gene expression, providing a detailed understanding of the complex biology underpinning tumor-host interactions. While there has been much focus on the genetic alterations associated with cancer cells and how they may impact treatment outcomes, how host genetics affects cancer development is also critical and will greatly determine treatment response. Genome-wide association studies (GWAS) have identified genetic variants associated with cancer predisposition. This approach has successfully identified host genetic risk factors associated with common thoracic cancers like lung cancer, but is less effective for rare cancers like malignant mesothelioma. To assess how host genetics impacts rare thoracic cancers, we used the Collaborative Cross (CC); a powerful murine genetic resource designed to maximize genetic diversity and rapidly identify genes associated with any biological trait. We are using the CC in conjunction with our asbestos-induced MexTAg mouse model, to identify host genes associated with mesothelioma development. Once genes that moderate tumor development and progression are known, human homologues can be identified and human datasets interrogated to validate their association with disease outcome. Furthermore, our CC-MexTAg animal model enables in-depth study of the tumor microenvironment, allowing the correlation of immune cell infiltration and gene expression signatures with disease development. This strategy provides a detailed picture of the underlying biological pathways associated with mesothelioma susceptibility and progression; knowledge that is crucial for the rational development of new diagnostic and therapeutic strategies. Here we discuss the influence of host genetics on developing an effective immune response to thoracic cancers. We highlight current knowledge gaps, and with a focus on mesothelioma, describe the development and application of the CC-MexTAg to overcome limitations and illustrate how the knowledge gained from this unique study will inform the rational design of future treatments of mesothelioma.}, } @article {pmid34234080, year = {2021}, author = {Ken Takahashi, }, title = {Asbestos Diseases Research Institute - A New WHO Collaborating Center.}, journal = {Industrial health}, volume = {59}, number = {3}, pages = {143-145}, pmid = {34234080}, issn = {1880-8026}, mesh = {Academies and Institutes ; *Asbestos/adverse effects ; *Asbestosis/epidemiology ; Humans ; *Mesothelioma ; *Occupational Exposure ; World Health Organization ; }, } @article {pmid34227091, year = {2021}, author = {Pagliuca, F and Zito Marino, F and Morgillo, F and Della Corte, C and Santini, M and Vicidomini, G and Guggino, G and De Dominicis, G and Campione, S and Accardo, M and Cozzolino, I and Franco, R}, title = {Inherited predisposition to malignant mesothelioma: germline BAP1 mutations and beyond.}, journal = {European review for medical and pharmacological sciences}, volume = {25}, number = {12}, pages = {4236-4246}, doi = {10.26355/eurrev_202106_26129}, pmid = {34227091}, issn = {2284-0729}, mesh = {Aged ; Female ; *Genetic Predisposition to Disease ; Germ-Line Mutation ; Humans ; Male ; Mesothelioma, Malignant/epidemiology/*genetics/pathology ; Middle Aged ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {Malignant mesothelioma (MM) is a rare aggressive neoplasm arising from mesothelial lining of body cavities, most commonly pleura and peritoneum. It is characterised by a poor prognosis and limited treatment options. A universally recognised risk factor for the development of MM is exposure to asbestos. However, evidence supporting a genetic susceptibility to the development of MM has been accumulating during the last decades. Intensive research for the identification of MM susceptibility genes has led to the discovery of BAP1 and to the definition of the so-called "BAP1-related tumour predisposition syndrome". Patients carrying germline BAP1 mutations have an increased risk for the early development of tumours, including MMs, uveal melanomas, cutaneous melanocytic lesions, clear cell renal cell carcinomas and basal cell carcinomas. Furthermore, pathogenic variants in tumour suppressor genes with a role in DNA repair have been recently described in families with clustered MM cases. These genetic alterations seem to confer exaggerate sensitivity to asbestos carcinogenic effect and, arguably, increased response to specific chemotherapeutic strategies. While the translational significance of BAP1 alterations is explored in the research field, the identification of families carrying germline BAP1 mutations is mandatory to start appropriate surveillance programs and guarantee the best clinical management to these patients.}, } @article {pmid34226685, year = {2021}, author = {Obacz, J and Yung, H and Shamseddin, M and Linnane, E and Liu, X and Azad, AA and Rassl, DM and Fairen-Jimenez, D and Rintoul, RC and Nikolić, MZ and Marciniak, SJ}, title = {Biological basis for novel mesothelioma therapies.}, journal = {British journal of cancer}, volume = {125}, number = {8}, pages = {1039-1055}, pmid = {34226685}, issn = {1532-1827}, support = {G1002610/MRC_/Medical Research Council/United Kingdom ; MR/R009120/1/MRC_/Medical Research Council/United Kingdom ; MR/S005579/1/MRC_/Medical Research Council/United Kingdom ; MR/V028669/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Asbestos/*toxicity ; Combined Modality Therapy ; Epigenesis, Genetic ; *Gene Regulatory Networks ; Humans ; Mesothelioma/chemically induced/genetics/pathology/*therapy ; Prognosis ; }, abstract = {Mesothelioma is an aggressive cancer that is associated with exposure to asbestos. Although asbestos is banned in several countries, including the UK, an epidemic of mesothelioma is predicted to affect middle-income countries during this century owing to their heavy consumption of asbestos. The prognosis for patients with mesothelioma is poor, reflecting a failure of conventional chemotherapy that has ultimately resulted from an inadequate understanding of its biology. However, recent work has revolutionised the study of mesothelioma, identifying genetic and pathophysiological vulnerabilities, including the loss of tumour suppressors, epigenetic dysregulation and susceptibility to nutrient stress. We discuss how this knowledge, combined with advances in immunotherapy, is enabling the development of novel targeted therapies.}, } @article {pmid34211838, year = {2021}, author = {Faversani, A and Favero, C and Dioni, L and Pesatori, AC and Bollati, V and Montoli, M and Musso, V and Terrasi, A and Fusco, N and Nosotti, M and Vaira, V and Palleschi, A}, title = {An EBC/Plasma miRNA Signature Discriminates Lung Adenocarcinomas From Pleural Mesothelioma and Healthy Controls.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {643280}, pmid = {34211838}, issn = {2234-943X}, abstract = {BACKGROUND: Despite significant improvement in screening programs for cancers of the respiratory district, especially in at-risk subjects, early disease detection is still a major issue. In this scenario, new molecular and non-invasive biomarkers are needed to improve early disease diagnosis.

METHODS: We profiled the miRNome in exhaled breath condensate (EBC) and plasma samples from fourteen patients affected by lung AdCa, nine healthy subjects. miRNA signatures were then analyzed in another neoplasia of the respiratory district, i.e. pleural mesothelioma (n = 23) and subjects previously exposed to asbestos were used as controls for this cohort (n = 19). Selected miRNAs were analyzed in purified pulmonary neoplastic or normal epithelial and stromal cell subpopulation from AdCa patients. Finally, the plasmatic miRNA signature was analyzed in a publicly available cohort of NSCLC patients for data validation and in silico analysis was performed with predicted miRNA targets using the multiMiR tool and STRING database.

RESULTS: miR-597-5p and miR-1260a are significantly over-expressed in EBC from lung AdCa and are associated with AdCa. Similarly, miR-1260a is also up-regulated in the plasma of AdCa patients together with miR-518f-3p and correlates with presence of lung cancer, whereas let-7f-5p is under-expressed. Analysis of these circulating miRNAs in pleural mesothelioma cases confirmed that up-regulation of miR-518f-3p, -597-5p and -1260a, is specific for lung AdCa. Lastly, quantification of the miRNAs in laser-assisted microdissected lung tissues revealed that miR-518f-3p, 597-5p and miR-1260a are predominantly expressed in tumor epithelial cells. Validation analysis confirmed miR-518f-3p as a possible circulating biomarker of NSCLC. In silico analysis of the potentially modulated biological processes by these three miRNAs, shows that tumor bioenergetics are the most affected pathways.

CONCLUSIONS: Overall, our data suggest a 3-miRNAs signature as a non-invasive and accurate biomarker of lung AdCa. This approach could supplement the current screening approaches for early lung cancer diagnosis.}, } @article {pmid34210265, year = {2021}, author = {Saracino, L and Bortolotto, C and Tomaselli, S and Fraolini, E and Bosio, M and Accordino, G and Agustoni, F and Abbott, DM and Pozzi, E and Eleftheriou, D and Morbini, P and Rinaldi, P and Primiceri, C and Lancia, A and Comoli, P and Filippi, AR and Stella, GM}, title = {Integrating data from multidisciplinary Management of Malignant Pleural Mesothelioma: a cohort study.}, journal = {BMC cancer}, volume = {21}, number = {1}, pages = {762}, pmid = {34210265}, issn = {1471-2407}, support = {Plagencell project//Fondazione Regionale per la Ricerca Biomedica/ ; }, mesh = {Cohort Studies ; Databases, Factual ; Female ; Humans ; Male ; Mesothelioma, Malignant/*epidemiology/mortality/*therapy ; Pleural Neoplasms/*epidemiology/mortality/*therapy ; Survival Analysis ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare and aggressive malignancy that most commonly affects the pleural layers. MPM has a strong association with asbestos, mainly caused by exposure to its biopersistent fibers in at least 80% of cases. Individuals with a chronic exposure to asbestos might develop disease with a 20-40-year latency with few or no symptoms. Such has been the case in the Italian regions of Piedmont and Lombardy, where industrial production of materials laden with asbestos, mainly cements, has been responsible for the onset of a large epidemic. Since 2018, a multidisciplinary team at San Matteo hospital in Pavia has been collecting data on over 100 patients with MPM. The main goal of this project is to define and describe an integrated profile for each MPM case at diagnosis by using data mining and partition analysis.

METHODS: Here we bring together exhaustive epidemiologic, histologic and radiologic data of 88 MPM patients that came to our observation and draw correlations with predictive and prognostic significance.

RESULTS: The median overall survival (OS) was 15.6 months. Most patients presented with pleural effusion, irrespective of disease stage. Quite unexpectedly, no statistically significant association was demonstrated between OS and TNM disease stage at diagnosis. Although average OS is similar in male and female patients, partition analysis of data underlined a significant differential hierarchy of predictor categories based on patient gender. In females with no smoking history, full chemotherapeutic regimens are associated with better outcomes. Moreover, concerning second line treatments, vinorelbine emerged as the most advantageous choice for female patients, whereas in the male subgroup no statistically significant difference resulted between gemcitabine and vinorelbine.

CONCLUSION: A multidisciplinary approach to MPM is mandatory to define better therapeutic approaches, personalize the management and improve patient outcomes.}, } @article {pmid34207798, year = {2021}, author = {Broggi, G and Angelico, G and Filetti, V and Ledda, C and Lombardo, C and Vitale, E and Rapisarda, V and Loreto, C and Caltabiano, R}, title = {Immunohistochemical Expression of Serine and Arginine-Rich Splicing Factor 1 (SRSF1) in Fluoro-Edenite-Induced Malignant Mesothelioma: A Preliminary Study.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {12}, pages = {}, pmid = {34207798}, issn = {1660-4601}, mesh = {Arginine ; Asbestos, Amphibole ; Biomarkers, Tumor/genetics ; Humans ; *Lung Neoplasms/chemically induced/genetics ; *Mesothelioma/chemically induced ; *Mesothelioma, Malignant ; RNA Splicing Factors ; Serine ; Serine-Arginine Splicing Factors/genetics ; }, abstract = {UNLABELLED: The Serine and Arginine-Rich Splicing Factor 1 (SRSF1) has a proto-oncogenic function, being associated with angiogenesis and frequently overexpressed in many human malignant neoplasms. Its immunohistochemical expression has never been investigated in malignant pleural mesothelioma (MPM). We evaluated SRSF1 immunoexpression and its possible relation to angiogenesis in a selected cohort of 10 fluoro-edenite(FE)-induced MPM cases.

METHODS: Immunohistochemical analyses with an anti-SRSF1 antibody were performed. We interpreted the cases as positive if tumor cell nuclei were stained; a semi-quantitative analysis of the cases was performed by evaluating the intensity of staining and the percentage of tumor positive cells. A microvessel density (MVD) count was also performed.

RESULTS: High and low immunoexpressions of SRSF1 were seen in six and four MPMs, respectively. A trend of shorter overall survival was found in FE-induced MPM patients with SRSF1 overexpression. In addition, a significant association between high-MVD and high SRSF1 immunoexpression (p = 0.0476) was found.

CONCLUSIONS: SRSF1 appears to be involved in MPM pathogenesis and its immunoexpression may represent a prognostic biomarker capable of identifying subgroups of patients with different prognosis. However, given the preliminary nature of the present study, further investigations on larger series, and additional in vitro studies, are required to validate our findings.}, } @article {pmid34206956, year = {2021}, author = {Désage, AL and Karpathiou, G and Peoc'h, M and Froudarakis, ME}, title = {The Immune Microenvironment of Malignant Pleural Mesothelioma: A Literature Review.}, journal = {Cancers}, volume = {13}, number = {13}, pages = {}, pmid = {34206956}, issn = {2072-6694}, abstract = {Malignant pleural mesothelioma (MPM) is a rare and aggressive tumour with a poor prognosis, associated with asbestos exposure. Nowadays, treatment is based on chemotherapy with a median overall survival of less than two years. This review highlights the main characteristics of the immune microenvironment in MPM with special emphasis on recent biological advances. The MPM microenvironment is highly infiltrated by tumour-associated macrophages, mainly M2-macrophages. In line with infiltration by M2-macrophages, which contribute to immune suppression, other effectors of innate immune response are deficient in MPM, such as dendritic cells or natural killer cells. On the other hand, tumour infiltrating lymphocytes (TILs) are also found in MPM, but CD4+ and CD8+ TILs might have decreased cytotoxic effects through T-regulators and high expression of immune checkpoints. Taken together, the immune microenvironment is particularly heterogeneous and can be considered as mainly immunotolerant or immunosuppressive. Therefore, identifying molecular vulnerabilities is particularly relevant to the improvement of patient outcomes and the assessment of promising treatment approaches.}, } @article {pmid34205400, year = {2021}, author = {Kwak, K and Cho, SI and Paek, D}, title = {Future Incidence of Malignant Mesothelioma in South Korea: Updated Projection to 2038.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {12}, pages = {}, pmid = {34205400}, issn = {1660-4601}, mesh = {*Asbestos/toxicity ; Female ; Humans ; Incidence ; Male ; *Mesothelioma/chemically induced/epidemiology ; *Mesothelioma, Malignant ; *Occupational Exposure ; Republic of Korea/epidemiology ; }, abstract = {Malignant mesothelioma (MM) is a cancer that is largely caused by exposure to asbestos. Although asbestos is no longer used in South Korea, the incidence of MM continues to increase due to its long latent period. We aimed to update the previous prediction of MM incidence until 2038. We predicted the incidence of MM over the next 20 years (2019-2038) in South Korea using Møller's age-period-cohort (APC) model and a Poisson regression model based on asbestos consumption. The APC model predicted that the crude incidence rate would increase sharply in men and slowly in women. Despite the sex discrepancy in the rate of increase, the incidence rate for both sexes is expected to continue increasing until 2038. In the Poisson model, the crude incidence rate was predicted to increase continuously until 2038, and far more cases of MM were predicted to occur compared with the results of the APC model. When compared with actual incidence data, the APC model was deemed more suitable than the Poisson model. The APC model predicted a continuous increase over the next 20 years with no peak, suggesting that the incidence of MM will continue to rise far into the future.}, } @article {pmid34201002, year = {2021}, author = {Coccè, V and La Monica, S and Bonelli, M and Alessandri, G and Alfieri, R and Lagrasta, CA and Madeddu, D and Frati, C and Flammini, L and Lisini, D and Marcianti, A and Parati, E and Paino, F and Giannì, A and Farronato, G and Falco, A and Spaggiari, L and Petrella, F and Pessina, A}, title = {Inhibition of Human Malignant Pleural Mesothelioma Growth by Mesenchymal Stromal Cells.}, journal = {Cells}, volume = {10}, number = {6}, pages = {}, pmid = {34201002}, issn = {2073-4409}, mesh = {Adolescent ; Adult ; Aged ; Animals ; *Cell Cycle ; Cell Line, Tumor ; *Cell Proliferation ; *Cell Survival ; Female ; Humans ; Mesenchymal Stem Cells ; Mesothelioma, Malignant/*pathology ; Mice ; Mice, Inbred BALB C ; Middle Aged ; Young Adult ; }, abstract = {BACKGROUND: Malignant Pleural Mesothelioma (MPM) is an aggressive tumor that has a significant incidence related to asbestos exposure with no effective therapy and poor prognosis. The role of mesenchymal stromal cells (MSCs) in cancer is controversial due to their opposite effects on tumor growth and in particular, only a few data are reported on MSCs and MPM.

METHODS: We investigated the in vitro efficacy of adipose tissue-derived MSCs, their lysates and secretome against different MPM cell lines. After large-scale production of MSCs in a bioreactor, their efficacy was also evaluated on a human MPM xenograft in mice.

RESULTS: MSCs, their lysate and secretome inhibited MPM cell proliferation in vitro with S or G0/G1 arrest of the cell cycle, respectively. MSC lysate induced cell death by apoptosis. The efficacy of MSC was confirmed in vivo by a significant inhibition of tumor growth, similar to that produced by systemic administration of paclitaxel. Interestingly, no tumor progression was observed after the last MSC treatment, while tumors started to grow again after stopping chemotherapeutic treatment.

CONCLUSIONS: These data demonstrated for the first time that MSCs, both through paracrine and cell-to-cell interaction mechanisms, induced a significant inhibition of human mesothelioma growth. Since the prognosis for MPM patients is poor and the options of care are limited to chemotherapy, MSCs could provide a potential new therapeutic approach for this malignancy.}, } @article {pmid34199722, year = {2021}, author = {Terenziani, R and Zoppi, S and Fumarola, C and Alfieri, R and Bonelli, M}, title = {Immunotherapeutic Approaches in Malignant Pleural Mesothelioma.}, journal = {Cancers}, volume = {13}, number = {11}, pages = {}, pmid = {34199722}, issn = {2072-6694}, abstract = {Malignant pleural mesothelioma (MPM) is a rare and aggressive malignant disease affecting the mesothelium, commonly associated to asbestos exposure. The current therapeutic actions, based on cisplatin/pemetrexed treatment, are limited due to the late stage at which most patients are diagnosed and to the intrinsic chemo-resistance of the tumor. Another relevant point is the absence of approved therapies in the second line setting following progression of MPM after chemotherapy. Considering the poor prognosis of the disease and the fact that the incidence of this tumor is expected to increase in the next decade, novel therapeutic approaches are urgently needed. In the last few years, several studies have investigated the efficacy and safety of immune-checkpoint inhibitors (ICIs) in the treatment of unresectable advanced MPM, and a number of trials with immunotherapeutic agents are ongoing in both first line and second line settings. In this review, we describe the most promising emerging immunotherapy treatments for MPM (ICIs, engineered T cells to express chimeric antigen receptors (CARs), dendritic cells (DCs) vaccines), focusing on the biological and immunological features of this tumor as well as on the issues surrounding clinical trial design.}, } @article {pmid34199544, year = {2021}, author = {Lorenzini, E and Ciarrocchi, A and Torricelli, F}, title = {Molecular Fingerprints of Malignant Pleural Mesothelioma: Not Just a Matter of Genetic Alterations.}, journal = {Journal of clinical medicine}, volume = {10}, number = {11}, pages = {}, pmid = {34199544}, issn = {2077-0383}, support = {//Italian Ministry of Health though Bando per la Valorizzazione della Ricerca in ambito Oncologico 2020-Fondi 5 per Mille/ ; //Italian Ministry of Health though Bando per la Valorizzazione della Ricerca in ambito Oncologico 2019-Fondi 5 per Mille/ ; }, abstract = {Malignant pleural mesothelioma (MPM) is a clinical emergency of our time. Being strongly associated with asbestos exposure, incidence of this cancer is ramping up these days in many industrialized countries and it will soon start to increase in many developing areas where the use of this silicate derivate is still largely in use. Deficiency of reliable markers for the early identification of these tumors and the limited efficacy of the currently available therapeutic options are the basis of the impressive mortality rate of MPM. These shortcomings reflect the very poor information available about the molecular basis of this disease. Results of the recently released deep profiling studies point to the epigenome as a central element in MPM development and progression. First, MPM is characterized by a low mutational burden and a highly peculiar set of mutations that hits almost exclusively epigenetic keepers or proteins controlling chromatin organization and function. Furthermore, asbestos does not seem to be associated with a distinctive mutational signature, while the precise mapping of epigenetic changes caused by this carcinogen has been defined, suggesting that alterations in epigenetic features are the driving force in the development of this disease. Last but not least, consistent evidence also indicates that, in the setting of MPM, chromatin rewiring and epigenetic alterations of cancer cells heavily condition the microenvironment, including the immune response. In this review we aim to point to the relevance of the epigenome in MPM and to highlight the dependency of this tumor on chromatin organization and function. We also intend to discuss the opportunity of targeting these mechanisms as potential therapeutic options for MPM.}, } @article {pmid34172838, year = {2023}, author = {Marant Micallef, C and Charvat, H and Houot, MT and Vignat, J and Straif, K and Paul, A and El Yamani, M and Pilorget, C and Soerjomataram, I}, title = {Estimated number of cancers attributable to occupational exposures in France in 2017: an update using a new method for improved estimates.}, journal = {Journal of exposure science & environmental epidemiology}, volume = {33}, number = {1}, pages = {125-131}, pmid = {34172838}, issn = {1559-064X}, support = {001/WHO_/World Health Organization/International ; }, mesh = {Female ; Humans ; Male ; *Asbestos ; Benzene ; Carcinogens ; Dust ; France/epidemiology ; *Lung Neoplasms/chemically induced/epidemiology ; *Occupational Diseases/epidemiology/etiology ; *Occupational Exposure ; Rubber ; }, abstract = {BACKGROUND: Over the last 50 years, occupational exposure to carcinogenic agents has been widely regulated in France.

OBJECTIVE: Report population-attributable fraction (PAF) and number of attributable cancer cases linked to occupational exposure in France based on an updated method to estimate lifetime occupational exposure prevalence.

METHODS: Population-level prevalence of lifetime exposure to ten carcinogenic agents (asbestos, benzene, chromium VI, diesel engine exhaust, formaldehyde, nickel compounds, polycyclic aromatic hydrocarbons, silica dust, trichloroethylene, wood dust) and two occupational circumstances (painters and rubber industry workers) were estimated using the French Census linked with MATGÉNÉ job-exposure matrices and French occupational surveys. PAF and number of attributable cancer cases were calculated using the estimated prevalence, relative risks from systematic review and national estimates of cancer incidence in 2017.

RESULTS: The lifetime occupational exposure prevalences were much higher in men than in women ranging from 0.2% (workers in the rubber industry) to 10.2% in men (silica), and from 0.10% (benzene, PAH and workers in the rubber industry) to 5.7% in women (formaldehyde). In total, 4,818 cancer cases (men: 4,223; women: 595) were attributable to the ten studied carcinogens and two occupational circumstances, representing 5.2% of cases among the studied cancer sites (M: 7.0%; W: 1.9%). In both sexes, mesothelioma (M: 689 cases; W: 160) and lung cancer (M: 3,032; W: 308) were the largest cancer sites impacted by the studied occupational agents and circumstances.

SIGNIFICANCE: A moderate proportion of the cancer cases in France is linked to carcinogens in occupational settings. Our method provides more precise estimates of attributable cancer taking into account evolution of exposure to occupational agents by sex, age and time. This methodology can be easily replicated using cross-sectional occupational data to aid priority making and implementation of prevention strategies in the workplace.}, } @article {pmid34161674, year = {2022}, author = {Ke, H and Kao, S and Lee, K and Takahashi, K and Goh, HP and Linton, A}, title = {The minimum standard of care for managing malignant pleural mesothelioma in developing nations within the Asia-Pacific Region.}, journal = {Asia-Pacific journal of clinical oncology}, volume = {18}, number = {3}, pages = {177-190}, doi = {10.1111/ajco.13611}, pmid = {34161674}, issn = {1743-7563}, mesh = {*Asbestos ; Developing Countries ; Humans ; *Lung Neoplasms/diagnosis/epidemiology/therapy ; *Mesothelioma/epidemiology/therapy ; *Mesothelioma, Malignant ; *Pleural Neoplasms/epidemiology/therapy ; Standard of Care ; }, abstract = {Malignant pleural mesothelioma (MPM) is an incurable malignancy associated with high symptom burden and poor prognosis. The relationship between asbestos exposure and MPM incidence is well-established. The incidence rate of MPM in Australia and New Zealand is among the highest globally. Matching the experience of other nations with legal restrictions on asbestos, incidence is expected to fall. In contrast, the incidence of MPM is rising in the developing nations of the Asia-Pacific as consumption and mining (albeit to a lesser extent) of asbestos continues. The incidence of MPM in these nations is currently low or unknown, reflecting insufficient latency periods since industrial use of asbestos, deficient resources for accurate diagnosis, and lack of occupational disease or cancer registries. The landscape of treatment for MPM is rapidly changing with combination immunotherapy now demonstrating improved survival in the first-line setting. Considering vast global inequity in access to anticancer treatments, establishing minimum standard of care for MPM in developing nations is of greater significance. Here, we review the evidence that form the basis of our minimum-standard recommendations for diagnosis, systemic treatment, management of recurrent pleural effusions, and symptom management. We also briefly review evidence-based treatment that may be considered for those with access.}, } @article {pmid34155270, year = {2021}, author = {Kishimoto, T and Kojima, Y and Fujimoto, N}, title = {Significance of secretory leukocyte peptidase inhibitor in pleural fluid for the diagnosis of benign asbestos pleural effusion.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {12965}, pmid = {34155270}, issn = {2045-2322}, mesh = {Area Under Curve ; Asbestosis/complications/*diagnosis/*metabolism ; *Biomarkers ; Biomarkers, Tumor ; Diagnosis, Differential ; Humans ; Mesothelioma, Malignant/diagnosis/etiology/metabolism ; Pleural Effusion/*diagnosis/etiology/*metabolism ; Pleural Effusion, Malignant/diagnosis/metabolism ; ROC Curve ; Secretory Leukocyte Peptidase Inhibitor/*metabolism ; }, abstract = {Secretory leukocyte peptidase inhibitor (SLPI) is a biomarker present in the respiratory tract that protects against tissue destruction and aids in wound healing. We examined whether SLPI in pleural effusion can be used to distinguish benign asbestos pleural effusion (BAPE) from early-stage malignant pleural mesothelioma (MPM) and other diseases. We measured the levels of SLPI, hyaluronic acid (HA), soluble mesothelin-related peptides (SMRP), CCL2, galectin-3, and CYFRA21-1 in 51 patients with BAPE, 37 patients with early-stage MPM, 77 patients with pleural effusions due to non-small-cell lung cancer (LCa), and 74 patients with other pleural effusions. SLPI levels in the pleural fluid of patients with BAPE were significantly lower than those in patients with MPM, LCa, and other pleural effusions (p < 0.0001). The area under the curve (AUC) for SLPI's ability to distinguish BAPE from MPM was 0.902, with a sensitivity of 82.4% and a specificity of 86.5%. This AUC was not only favourable but was better than the AUC for the ability of CYFRA21-1 to distinguish BAPE (0.853). The combination of SLPI and CYFRA21-1 achieved an AUC of 0.965 for the differentiation between BAPE and MPM. Pleural fluid SLPI as well as CYFRA21-1 and HA is useful as a biomarker to diagnose BAPE, which needs to be distinguished from early-stage MPM.}, } @article {pmid34120777, year = {2022}, author = {Ramada Rodilla, JM and Calvo Cerrada, B and Serra Pujadas, C and Delclos, GL and Benavides, FG}, title = {Fiber burden and asbestos-related diseases: an umbrella review.}, journal = {Gaceta sanitaria}, volume = {36}, number = {2}, pages = {173-183}, pmid = {34120777}, issn = {1578-1283}, support = {P30 ES030285/ES/NIEHS NIH HHS/United States ; T42 OH008421/OH/NIOSH CDC HHS/United States ; }, mesh = {*Asbestos/toxicity ; Asbestos, Amphibole ; Humans ; *Lung Neoplasms/chemically induced/epidemiology ; *Mesothelioma/chemically induced/etiology ; *Occupational Exposure/adverse effects ; Risk Assessment ; }, abstract = {OBJECTIVE: What are the levels of asbestos exposure that cause each type of health effect? The objective of this study was to review the available scientific evidence on exposure levels for asbestos and their relationship to health effects.

METHOD: An umbrella review of English-language reviews and meta-analyses, from 1980 to March 2021 was conducted. We included reviews involving quantified asbestos exposures and health outcomes. The review has been adapted to the indications of the PRISMA declaration. Methodological quality of the selected studies was assessed using the AMSTAR instrument.

RESULTS: We retrieved 196 references. After applying the search strategy and quality analysis, 10 reviews were selected for in-depth analysis. For lung cancer, the highest risk was observed with exposure to amphiboles. Longer, thinner fibers had the greatest capacity to cause lung cancer, especially those > 10 μm in length. For mesothelioma, longer and thinner fibers were also more pathogenic; amphiboles ≥ 5 μm are especially associated with increased mesothelioma risk. No studies observed an increased risk for lung cancer or mesothelioma at asbestos exposure levels <0.1 f/ml. No reviews provided information on exposure concentrations for pulmonary fibrosis. Currently, there is limited evidence in humans to establish the causal relationship between gastrointestinal cancer and asbestos exposure.

CONCLUSIONS: Banning all asbestos exposure remains the best measure to preventing its negative health effects. The highest quality reviews and meta-analyses support that there is little risk of lung cancer or mesothelioma at daily exposure levels below 0.1 f/ml.}, } @article {pmid34116230, year = {2021}, author = {Tsim, S and Alexander, L and Kelly, C and Shaw, A and Hinsley, S and Clark, S and Evison, M and Holme, J and Cameron, EJ and Sharma, D and Wright, A and Grundy, S and Grieve, D and Ionescu, A and Breen, DP and Paramasivam, E and Psallidas, I and Mukherjee, D and Chetty, M and Cox, G and Hart-Thomas, A and Naseer, R and Edwards, J and Daneshvar, C and Panchal, R and Munavvar, M and Ostroff, R and Alexander, L and Hall, H and Neilson, M and Miller, C and McCormick, C and Thomson, F and Chalmers, AJ and Maskell, NA and Blyth, KG}, title = {Serum Proteomics and Plasma Fibulin-3 in Differentiation of Mesothelioma From Asbestos-Exposed Controls and Patients With Other Pleural Diseases.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {16}, number = {10}, pages = {1705-1717}, pmid = {34116230}, issn = {1556-1380}, support = {29801/CRUK_/Cancer Research UK/United Kingdom ; A29801/CRUK_/Cancer Research UK/United Kingdom ; A31287/CRUK_/Cancer Research UK/United Kingdom ; A17196/CRUK_/Cancer Research UK/United Kingdom ; 15960/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {*Asbestos ; Biomarkers, Tumor ; Calcium-Binding Proteins ; Extracellular Matrix Proteins ; GPI-Linked Proteins ; Humans ; *Lung Neoplasms/diagnosis ; *Mesothelioma/diagnosis/etiology ; *Pleural Neoplasms/diagnosis/etiology ; Proteomics ; Retrospective Studies ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is difficult to diagnose. An accurate blood biomarker could prompt specialist referral or be deployed in future screening. In earlier retrospective studies, SOMAscan proteomics (Somalogic, Boulder, CO) and fibulin-3 seemed highly accurate, but SOMAscan has not been validated prospectively and subsequent fibulin-3 data have been contradictory.

METHODS: A multicenter prospective observational study was performed in 22 centers, generating a large intention-to-diagnose cohort. Blood sampling, processing, and diagnostic assessment were standardized, including a 1-year follow-up. Plasma fibulin-3 was measured using two enzyme-linked immunosorbent assays (CloudClone [used in previous studies] and BosterBio, Pleasanton, CA). Serum proteomics was measured using the SOMAscan assay. Diagnostic performance (sensitivity at 95% specificity, area under the curve [AUC]) was benchmarked against serum mesothelin (Mesomark, Fujirebio Diagnostics, Malvern, PA). Biomarkers were correlated against primary tumor volume, inflammatory markers, and asbestos exposure.

RESULTS: A total of 638 patients with suspected pleural malignancy (SPM) and 110 asbestos-exposed controls (AECs) were recruited. SOMAscan reliably differentiated MPM from AECs (75% sensitivity, 88.2% specificity, validation cohort AUC 0.855) but was not useful in patients with differentiating non-MPM SPM. Fibulin-3 (by BosterBio after failed CloudClone validation) revealed 7.4% and 11.9% sensitivity at 95% specificity in MPM versus non-MPM SPM and AECs, respectively (associated AUCs 0.611 [0.557-0.664], p = 0.0015) and 0.516 [0.443-0.589], p = 0.671), both inferior to mesothelin. SOMAscan proteins correlated with inflammatory markers but not with asbestos exposure. Neither biomarker correlated with tumor volume.

CONCLUSIONS: SOMAscan may prove useful as a future screening test for MPM in asbestos-exposed persons. Neither fibulin-3 nor SOMAscan should be used for diagnosis or pathway stratification.}, } @article {pmid34082107, year = {2021}, author = {Vandenhoeck, J and van Meerbeeck, JP and Fransen, E and Raskin, J and Van Camp, G and Op de Beeck, K and Lamote, K}, title = {DNA Methylation as a Diagnostic Biomarker for Malignant Mesothelioma: A Systematic Review and Meta-Analysis.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {16}, number = {9}, pages = {1461-1478}, doi = {10.1016/j.jtho.2021.05.015}, pmid = {34082107}, issn = {1556-1380}, mesh = {*Asbestos/adverse effects ; Biomarkers, Tumor/genetics/metabolism ; DNA Methylation ; Humans ; *Lung Neoplasms/diagnosis/genetics ; *Mesothelioma/diagnosis/genetics ; *Mesothelioma, Malignant ; }, abstract = {Malignant mesothelioma is an aggressive cancer type linked to asbestos exposure. Because of several intrinsic challenges, mesothelioma is often diagnosed in an advanced disease stage. Therefore, there is a need for diagnostic biomarkers that may contribute to early detection. Recently, the epigenome of tumors is being extensively investigated to identify biomarkers. This manuscript is a systematic review summarizing the state-of-the-art research investigating DNA methylation in mesothelioma. Four literature databases (PubMed, Scopus, Web of Science, MEDLINE) were systematically searched for studies investigating DNA methylation in mesothelioma up to October 16, 2020. A meta-analysis was performed per gene investigated in at least two independent studies. A total of 53 studies investigated DNA methylation of 97 genes in mesothelioma and are described in a qualitative overview. Furthermore, ten studies investigating 13 genes (APC, CDH1, CDKN2A, DAPK, ESR1, MGMT, miR-34b/c, PGR, RARβ, RASSF1, SFRP1, SFRP4, WIF1) were included in the quantitative meta-analysis. In this meta-analysis, the APC gene is significantly hypomethylated in mesothelioma, whereas CDH1, ESR1, miR-34b/c, PGR, RARβ, SFRP1, and WIF1 are significantly hypermethylated in mesothelioma. The three genes that are the most appropriate candidate biomarkers from this meta-analysis are APC, miR-34b/c, and WIF1. Nevertheless, both study number and study objects comprised in this meta-analysis are too low to draw final conclusions on their clinical applications. The elucidation of the genome-wide DNA methylation profile of mesothelioma is desirable in the future, using a standardized genome-wide methylation analysis approach. The most informative CpG sites from this signature could then form the basis of a panel of highly sensitive and specific biomarkers that can be used for the diagnosis of mesothelioma and even for the screening of an at high-risk population of asbestos-exposed individuals.}, } @article {pmid34073720, year = {2021}, author = {Napoli, F and Listì, A and Zambelli, V and Witel, G and Bironzo, P and Papotti, M and Volante, M and Scagliotti, G and Righi, L}, title = {Pathological Characterization of Tumor Immune Microenvironment (TIME) in Malignant Pleural Mesothelioma.}, journal = {Cancers}, volume = {13}, number = {11}, pages = {}, pmid = {34073720}, issn = {2072-6694}, support = {IG 2019 - ID. 23760 project//Associazione Italiana per la Ricerca sul Cancro/ ; Ricerca Locale 2019//Università degli Studi di Torino/ ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare and highly aggressive disease that arises from pleural mesothelial cells, characterized by a median survival of approximately 13-15 months after diagnosis. The primary cause of this disease is asbestos exposure and the main issues associated with it are late diagnosis and lack of effective therapies. Asbestos-induced cellular damage is associated with the generation of an inflammatory microenvironment that influences and supports tumor growth, possibly in association with patients' genetic predisposition and tumor genomic profile. The chronic inflammatory response to asbestos fibers leads to a unique tumor immune microenvironment (TIME) composed of a heterogeneous mixture of stromal, endothelial, and immune cells, and relative composition and interaction among them is suggested to bear prognostic and therapeutic implications. TIME in MPM is known to be constituted by immunosuppressive cells, such as type 2 tumor-associated macrophages and T regulatory lymphocytes, plus the expression of several immunosuppressive factors, such as tumor-associated PD-L1. Several studies in recent years have contributed to achieve a greater understanding of the pathogenetic mechanisms in tumor development and pathobiology of TIME, that opens the way to new therapeutic strategies. The study of TIME is fundamental in identifying appropriate prognostic and predictive tissue biomarkers. In the present review, we summarize the current knowledge about the pathological characterization of TIME in MPM.}, } @article {pmid34071989, year = {2021}, author = {Cugliari, G and Allione, A and Russo, A and Catalano, C and Casalone, E and Guarrera, S and Grosso, F and Ferrante, D and Sculco, M and La Vecchia, M and Pirazzini, C and Libener, R and Mirabelli, D and Magnani, C and Dianzani, I and Matullo, G}, title = {New DNA Methylation Signals for Malignant Pleural Mesothelioma Risk Assessment.}, journal = {Cancers}, volume = {13}, number = {11}, pages = {}, pmid = {34071989}, issn = {2072-6694}, abstract = {Malignant pleural mesothelioma (MPM) is a rare and aggressive neoplasm. Patients are usually diagnosed when current treatments have limited benefits, highlighting the need for noninvasive tests aimed at an MPM risk assessment tool that might improve life expectancy. Three hundred asbestos-exposed subjects (163 MPM cases and 137 cancer-free controls), from the same geographical region in Italy, were recruited. The evaluation of asbestos exposure was conducted considering the frequency, the duration and the intensity of occupational, environmental and domestic exposure. A genome-wide methylation array was performed to identify novel blood DNA methylation (DNAm) markers of MPM. Multiple regression analyses adjusting for potential confounding factors and interaction between asbestos exposure and DNAm on the MPM odds ratio were applied. Epigenome-wide analysis (EWAS) revealed 12 single-CpGs associated with the disease. Two of these showed high statistical power (99%) and effect size (>0.05) after false discovery rate (FDR) multiple comparison corrections: (i) cg03546163 in FKBP5, significantly hypomethylated in cases (Mean Difference in beta values (MD) = -0.09, 95% CI = -0.12|-0.06, p = 1.2 × 10[-7]), and (ii) cg06633438 in MLLT1, statistically hypermethylated in cases (MD = 0.07, 95% CI = 0.04|0.10, p = 1.0 × 10[-6]). Based on the interaction analysis, asbestos exposure and epigenetic profile together may improve MPM risk assessment. Above-median asbestos exposure and hypomethylation of cg03546163 in FKBP5 (OR = 20.84, 95% CI = 8.71|53.96, p = 5.5 × 10[-11]) and hypermethylation of cg06633438 in MLLT1 (OR = 11.71, 95% CI = 4.97|29.64, p = 5.9 × 10[-8]) genes compared to below-median asbestos exposure and hyper/hypomethylation of single-CpG DNAm, respectively. Receiver Operation Characteristics (ROC) for Case-Control Discrimination showed a significant increase in MPM discrimination when DNAm information was added in the model (baseline model, BM: asbestos exposure, age, gender and white blood cells); area under the curve, AUC = 0.75; BM + cg03546163 at FKBP5. AUC = 0.89, 2.1 × 10[-7]; BM + cg06633438 at MLLT1. AUC = 0.89, 6.3 × 10[-8]. Validation and replication procedures, considering independent sample size and a different DNAm analysis technique, confirmed the observed associations. Our results suggest the potential application of DNAm profiles in blood to develop noninvasive tests for MPM risk assessment in asbestos-exposed subjects.}, } @article {pmid34070888, year = {2021}, author = {Rossi, G and Davoli, F and Poletti, V and Cavazza, A and Lococo, F}, title = {When the Diagnosis of Mesothelioma Challenges Textbooks and Guidelines.}, journal = {Journal of clinical medicine}, volume = {10}, number = {11}, pages = {}, pmid = {34070888}, issn = {2077-0383}, abstract = {The diagnosis of malignant mesothelioma (MPM) does not pose difficulties when presenting with usual clinico-radiologic features and morphology. Pathology textbooks and national/international guidelines generally describe the findings of classic MPM, underlining common clinical presentation, the gold standard of sampling techniques, usual morphologic variants, immunohistochemical results of several positive and negative primary antibodies in the differential diagnosis, and the role of novel molecular markers. Nevertheless, MPM often does not follow the golden rules in routine practice, while the literature generally does not sufficiently emphasize unusual features of its manifestation. This gap may potentially create problems for patients in sustaining a difficult diagnosis of MPM in clinical practice and during legal disputes. Indeed, the guidelines accidentally tend to favor the job of lawyers and pathologists defending asbestos-producing industries against patients suffering from MPM characterized by uncommon features. The current review is aimed at underlining the wide spectrum of clinical and radiological presentation of MPM, the possibility to consistently use cytology for diagnostic intent, the aberrant immunohistochemical expression using so-called specific negative and positive primary antibodies, and finally proposing some alternative and more unbiased approaches to the diagnosis of MPM.}, } @article {pmid34069196, year = {2021}, author = {Lee, KM and Godderis, L and Furuya, S and Kim, YJ and Kang, D}, title = {Comparison of Asbestos Victim Relief Available Outside of Conventional Occupational Compensation Schemes.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {10}, pages = {}, pmid = {34069196}, issn = {1660-4601}, mesh = {*Asbestos ; France ; Humans ; Japan ; *Lung Neoplasms ; *Mesothelioma/chemically induced ; Netherlands ; *Occupational Diseases ; *Occupational Exposure ; Republic of Korea ; United Kingdom ; Workers' Compensation ; }, abstract = {The asbestos victim relief schemes were introduced to resolve the issue of victims of asbestos-related diseases not receiving compensation through conventional legal orders. This article seeks to derive the differences and commonalities of various asbestos victim relief schemes available outside of the conventional occupational compensation system along with a systematic understanding and to propose plans for improvement through a comparative study. After the degree of asbestos exposure, the population, and the period of implementation were corrected, the recognized claims of the total of conventional occupational compensation schemes and the asbestos victim relief schemes could be ranked in the order of South Korea (KOR) (1867, total), France (FRA) (1571), Japan (JPN) (966), KOR (847, asbestosis grade 2,3 excluded), the United Kingdom (GBR) (670), and the Netherlands (NLD) (95). The average amount of compensation per person, in the case of mesothelioma, was higher in the order of FRA (4.60 times), KOR (1.46 times), GBR (1.03 times), and NLD (0.73 times) of the median income per year. The differences between countries were largely caused by the purpose of institutional design and influenced by the level of qualification, the existence of an expiration date, type of disease, type of benefit, level of judgment criteria, the existence of a procedure for appeals, and recognition rate (GBR: 102%, FRA: 84%, NLD: 81%, JPN: 76%, KOR: 73%, and BEL: 54%). Based on this analysis, suggestions could be made regarding the expansion of disease types, benefit types, and the overall review of judgment criteria.}, } @article {pmid34068638, year = {2021}, author = {Vimercati, L and Cavone, D and Delfino, MC and Bruni, B and De Maria, L and Caputi, A and Sponselli, S and Rossi, R and Resta, L and Fortarezza, F and Pezzuto, F and Serio, G}, title = {Primary Ovarian Mesothelioma: A Case Series with Electron Microscopy Examination and Review of the Literature.}, journal = {Cancers}, volume = {13}, number = {9}, pages = {}, pmid = {34068638}, issn = {2072-6694}, abstract = {Primary ovarian mesothelioma is a rare, aggressive neoplastic disease with a poor prognosis. At onset, the tumor is only rarely limited to the ovaries and usually already widespread in the peritoneum. The rarity of this entity and the difficulties differentiating it from either ovarian carcinoma or peritoneal mesothelioma may lead to frequent misdiagnoses and may raise some concerns about its histogenesis. Thus, reporting such rare cases is fundamental to gain greater awareness of this neoplasm and try to answer unsolved questions. Herein, we described four cases of histological diagnoses of ovarian mesothelioma extrapolated by the regional mesothelioma register of Apulia (southern Italy). In all cases, a detailed medical history was collected according to national mesothelioma register guidelines. A broad panel of antibodies was used for immunohistochemistry to confirm the diagnoses. Moreover, ovarian tissue samples were also examined by transmission and scanning electron microscopy, detecting asbestos fibers and talc crystals in two cases. Because of the few cases described, we reviewed the English literature in the Medline database, focusing on articles about ovarian mesothelioma "misclassification", "misdiagnosis", "diagnostic challenge" or "diagnostic pitfall" and on unsolved questions about its histogenesis and possible risk factors.}, } @article {pmid34066159, year = {2021}, author = {Anobile, DP and Bironzo, P and Picca, F and Lingua, MF and Morena, D and Righi, L and Napoli, F and Papotti, MG and Pittaro, A and Di Nicolantonio, F and Gigliotti, C and Bussolino, F and Comunanza, V and Guerrera, F and Sandri, A and Leo, F and Libener, R and Aviles, P and Novello, S and Taulli, R and Scagliotti, GV and Riganti, C}, title = {Evaluation of the Preclinical Efficacy of Lurbinectedin in Malignant Pleural Mesothelioma.}, journal = {Cancers}, volume = {13}, number = {10}, pages = {}, pmid = {34066159}, issn = {2072-6694}, support = {23760//Associazione Italiana per la Ricerca sul Cancro/ ; 21408//Associazione Italiana per la Ricerca sul Cancro/ ; EX60% Funding 2019//Ministero dell'Istruzione, dell'Università e della Ricerca/ ; TOPMESO JTC 2017//ERANet Transcan2/ ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a highly aggressive cancer generally diagnosed at an advanced stage and characterized by a poor prognosis. The absence of alterations in druggable kinases, together with an immune-suppressive tumor microenvironment, limits the use of molecular targeted therapies, making the treatment of MPM particularly challenging. Here we investigated the in vitro susceptibility of MPM to lurbinectedin (PM01183), a marine-derived drug that recently received accelerated approval by the FDA for the treatment of patients with metastatic small cell lung cancer with disease progression on or after platinum-based chemotherapy.

METHODS: A panel of primary MPM cultures, resembling the three major MPM histological subtypes (epithelioid, sarcomatoid, and biphasic), was characterized in terms of BAP1 status and histological markers. Subsequently, we explored the effects of lurbinectedin at nanomolar concentration on cell cycle, cell viability, DNA damage, genotoxic stress response, and proliferation.

RESULTS: Stabilized MPM cultures exhibited high sensitivity to lurbinectedin independently from the BAP1 mutational status and histological classification. Specifically, we observed that lurbinectedin rapidly promoted a cell cycle arrest in the S-phase and the activation of the DNA damage response, two conditions that invariably resulted in an irreversible DNA fragmentation, together with strong apoptotic cell death. Moreover, the analysis of long-term treatment indicated that lurbinectedin severely impacts MPM transforming abilities in vitro.

CONCLUSION: Overall, our data provide evidence that lurbinectedin exerts a potent antitumoral activity on primary MPM cells, independently from both the histological subtype and BAP1 alteration, suggesting its potential activity in the treatment of MPM patients.}, } @article {pmid34060417, year = {2021}, author = {Ierardi, AM and Mathis, C and Urban, A and Jacobs, N and Finley, B and Gaffney, S}, title = {Potential airborne asbestos exposures in dentistry: a comprehensive review and risk assessment.}, journal = {Critical reviews in toxicology}, volume = {51}, number = {4}, pages = {301-327}, doi = {10.1080/10408444.2021.1910624}, pmid = {34060417}, issn = {1547-6898}, mesh = {Air Pollutants, Occupational/*analysis ; *Asbestos ; Asbestos, Serpentine ; *Dentistry ; Environmental Monitoring ; Humans ; Lung Neoplasms ; Mesothelioma/chemically induced/epidemiology ; No-Observed-Adverse-Effect Level ; Occupational Exposure/*statistics & numerical data ; Risk Assessment ; }, abstract = {Chrysotile was formerly used in the manufacture of casting ring liner (CRL) and periodontal dressing powder (PDP). The purpose of this study was to describe the potential for airborne asbestos exposure among dental professionals who may have used these products and to assess their risk of asbestos-related disease (ARD). Task-specific exposure data associated with CRL and PDP were identified and compared to regulatory standards for asbestos and health-based benchmarks. Personal airborne fiber concentrations ranged from 0.008-3.5 f/cc by PCM (duration: 3-420 minutes) for CRL (tearing, placement), and from <0.0044-<0.297 f/cc by PCM (duration: 5-28 minutes) for PDP (mixing). Eight-hour time-weighted average (TWA) exposures were calculated using the reported task-based airborne fiber concentrations and associated sampling durations. For CRL tasks, the upper-bound calculated 8-hour TWA of 0.022 f/cc (tearing, placement) did not exceed regulatory standards for asbestos (≥0.1 f/cc). All samples collected during the mixing of PDP resulted in non-measurable fiber concentrations. The greatest estimated cumulative asbestos exposure for dental professionals using CRL (tearing, placement) of 0.33 f/cc-years is well below "best estimate", published chrysotile no-observed-adverse-effect-levels (NOAEL) for ARD (lung cancer = 89-168 f/cc-years; pleural mesothelioma = 208-415 f/cc-years). As such, the use of asbestos-containing CRL and/or PDP is not expected to pose an increased risk of ARD among dental professionals. This conclusion is consistent with the lack of an increased risk of ARD reported in epidemiological studies of these occupations.}, } @article {pmid34059094, year = {2021}, author = {Haakensen, VD and Nowak, AK and Ellingsen, EB and Farooqi, SJ and Bjaanæs, MM and Horndalsveen, H and Mcculloch, T and Grundberg, O and Cedres, SM and Helland, Å}, title = {NIPU: a randomised, open-label, phase II study evaluating nivolumab and ipilimumab combined with UV1 vaccination as second line treatment in patients with malignant mesothelioma.}, journal = {Journal of translational medicine}, volume = {19}, number = {1}, pages = {232}, pmid = {34059094}, issn = {1479-5876}, mesh = {Antineoplastic Combined Chemotherapy Protocols ; Humans ; Ipilimumab/therapeutic use ; *Mesothelioma/drug therapy ; *Mesothelioma, Malignant ; Nivolumab/therapeutic use ; Vaccination ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare and aggressive tumour. For patients with inoperable disease, few treatment options are available after first line chemotherapy. The combination of ipilimumab and nivolumab has recently shown increased survival compared to standard chemotherapy, but most patients do not respond and improvements are called for. Telomerase is expressed in mesothelioma cells, but only sparsely in normal tissues and is therefore an attractive target for therapeutic vaccination. Vaccination against telomerase is tolerable and has shown to induce immune responses associated with increased survival in other cancer types. There is a well-founded scientific rationale for the combination of a telomerase vaccine and checkpoint inhibition to improve treatment response in MPM patients.

METHODS: NIPU is a randomized, multi-centre, open-label, phase II study comparing the efficacy and safety of nivolumab and ipilimumab with or without telomerase vaccine in patients with inoperable malignant pleural mesothelioma after first-line platinum-based chemotherapy. Participants (n = 118) are randomized 1:1 into two treatment arms. All participants receive treatment with nivolumab (240 mg every 2 weeks) and ipilimumab (1 mg/kg every 6 weeks) until disease progression, unacceptable toxicity or for a maximum of 2 years. Patients randomised to the experimental arm receive 8 intradermal injections of UV1 vaccine during the first three months of treatment. Tumour tissue, blood, urine, faeces and imaging will be collected for biomarker analyses and exploration of mechanisms for response and resistance to therapy.

DISCUSSION: Checkpoint inhibition is used for treatment of mesothelioma, but many patients still do not respond. Increasing therapy response to immunotherapy is an important goal. Possible approaches include combination with chemotherapy, radiotherapy, targeted therapy and other immunotherapeutic agents. Predictive biomarkers are necessary to ensure optimal treatment for each patient and to prevent unnecessary side effects. This trial seeks to improve treatment response by combining checkpoint inhibition with a telomerase vaccine and also to explore mechanisms for treatment response and resistance. Knowledge gained in the NIPU study may be transferred to the first line setting and to other cancers with limited benefit from immunotherapy.

TRIAL REGISTRATION: ClinicalTrials.gov: NCT04300244, registered March 8th, 2020, https://clinicaltrials.gov/ct2/show/NCT04300244?term=NIPU&draw=2&rank=1 .}, } @article {pmid34052509, year = {2021}, author = {Scarselli, A and Marinaccio, A and Iavicoli, S}, title = {Ophiolitic outcrops, naturally occurring asbestos exposure and mortality risk from malignant mesothelioma in Calabria (Southern Italy).}, journal = {Public health}, volume = {195}, number = {}, pages = {57-60}, doi = {10.1016/j.puhe.2021.04.008}, pmid = {34052509}, issn = {1476-5616}, mesh = {*Asbestos/toxicity ; Environmental Exposure/adverse effects ; Female ; Humans ; Italy/epidemiology ; *Lung Neoplasms/epidemiology ; Male ; *Mesothelioma, Malignant ; *Occupational Diseases/epidemiology ; *Occupational Exposure/adverse effects ; }, abstract = {OBJECTIVES: Naturally occurring asbestos from ophiolitic outcrops can pose a health risk to the resident population. Some studies have documented this risk of exposure in many areas around the world. The aim of the study is to estimate the possible impact on health caused by asbestos outcrops present in some areas of Calabria, a region of southern Italy.

STUDY DESIGN: The design of the study is observational and uses routinely collected data on employment, compensations and mortality.

METHODS: Data from archives of mortality in the period 2005-2015 were selected. Standardized mortality ratio (SMR) for malignant mesothelioma (MM) by municipalities of residence with reference to the regional population was estimated assuming a Poisson distribution of the data. Administrative archives of companies' employment records and occupational disease compensation data were used to exclude occupational origin cases.

RESULTS: A total of 163 cases of MM were identified. Statistically significant excess risks (P-value <0.05) were observed for several municipalities, some of which were located in areas where asbestos outcrops had previously been identified. Significant SMRs vary between 44.0 and 5.2. The mean age at death in the areas at risk of ophiolitic outcrops ranges from 65.4 to 77.1 years, and the gender ratio (male/female) ranges from 0.66 to 1.3.

CONCLUSIONS: Monitoring of areas most involved in the risk of environmental contamination from ophiolitic outcrops is highly suggested. Full implementation of the local MM surveillance system is strongly encouraged. Further investigations are recommended to specifically identify the cause of exposure and confirm the hypothesis of a causal association with asbestos naturally occurring in these risk areas.}, } @article {pmid34040906, year = {2021}, author = {Thomas, A and Karakattu, S and Cagle, J and Hoskere, G}, title = {Malignant Pleural Mesothelioma Epidemiology in the United States From 2000 to 2016.}, journal = {Cureus}, volume = {13}, number = {4}, pages = {e14605}, pmid = {34040906}, issn = {2168-8184}, abstract = {Introduction Pleural mesothelioma constitutes about 80% of all mesotheliomas. The peak incidence of malignant mesothelioma estimated using the cancer registries was in early 1990 to 2000 in the United States. The disease is primarily associated with asbestos exposure. The latency period between asbestos exposure and the development of malignant pleural mesothelioma (MPM) can range anywhere from 15 to 60 years. Asbestos exposure was peaked during the industrial revolution and World War II due to military and shipyard exposures. It is often difficult for the pathologist to distinguish different histological subtypes; due to the disease's rarity and the inadequate tissue sample obtained. There is no available data on the difference in epidemiology of different subtypes of MPM. Surveillance Epidemiology and End Results (SEER), cancer incidence data include population-based registries covering approximately 34.6% of the U.S. population. Here in our study, we analyze malignant pleural mesothelioma epidemiology in the United States, emphasizing different histological subtypes. Methods SEER data from 2000 to 2016 was used in our study. The primary site of cancer is selected as pleura, and malignant behavior only is selected as the filter. Data were analyzed using the SEER stat program. Overall epidemiology of MPM and epidemiology of epithelioid, fibrous, and biphasic histological subtypes were analyzed separately. We used annual percentage change (APC) to evaluate the trend in the epidemiology of MPM. Results summary A total of 11,857 cases of MPM were included in the primary cohort from the SEER 18 registry from 2000 to 2016. The total prevalence of MPM was highest in 2009 and was lowest in 2016. The APC in MPM incidence during this period is -2.0. After removing 5,989 cases with non-specified histology during the same period, the APC for each histological type is -0.7 for fibrous type, 1.8 for epithelioid type, and 2.9 for biphasic type. Out of 17 regional registries included in the study, the greatest statistically significant change in APC was seen in the Hawaiian registry -4.1. In contrast, the lowest statistically significant difference was seen in Seattle (Puget Sound) registry -1.7. The APC in the incidence of MPM among males during the study period was -2.4 while that of females was -0.9. The Iowa registry showed a statistically significant increase in APC of the epithelioid malignant mesothelioma with a statistically insignificant reduction in the overall MPM APC. Conclusion The overall incidence of MPM in the United States is declining, while the data showed an increase in the incidence of epithelioid and biphasic histological subtypes. The authors believe that these conflicting results can be attributed to improved histological diagnosis and improved biopsy techniques.}, } @article {pmid34036634, year = {2021}, author = {Baur, X and Frank, AL and Soskolne, CL and Oliver, LC and Magnani, C}, title = {Malignant mesothelioma: Ongoing controversies about its etiology in females.}, journal = {American journal of industrial medicine}, volume = {64}, number = {7}, pages = {543-550}, doi = {10.1002/ajim.23257}, pmid = {34036634}, issn = {1097-0274}, mesh = {*Asbestos/toxicity ; Female ; Humans ; Incidence ; Male ; *Mesothelioma/epidemiology/etiology ; *Mesothelioma, Malignant ; *Occupational Exposure/adverse effects ; *Pleural Neoplasms ; }, abstract = {Malignant mesothelioma (MM) is one of the most aggressive cancers with the poorest of outcomes. There is no doubt that mesothelioma in males is related to asbestos exposure, but some authors suggest that most of the cases diagnosed in females are "idiopathic." In our assessment of the science, the "low risk" of mesothelioma in females is because of the nonsystematic recording of exposure histories among females. Indeed, asbestos exposure is mentioned in only some of the studies that include females. We estimate the risk of MM among females to be close to that in males. The absence of detailed exposure histories should be rectified in future studies involving women. As a matter of social justice, the ongoing failure to recognize asbestos as the cause of a majority of cases of MM in females does them, and their kin, a profound disservice.}, } @article {pmid34033161, year = {2022}, author = {Louw, A and Lee, YCG and Acott, N and Creaney, J and van Vliet, C and Chai, SM}, title = {Diagnostic utility of BAP1 for malignant pleural mesothelioma in pleural fluid specimens with atypical morphology.}, journal = {Cytopathology : official journal of the British Society for Clinical Cytology}, volume = {33}, number = {1}, pages = {84-92}, doi = {10.1111/cyt.13015}, pmid = {34033161}, issn = {1365-2303}, mesh = {Biomarkers, Tumor/metabolism ; Humans ; *Lung Neoplasms/diagnosis/genetics/metabolism ; *Mesothelioma/pathology ; *Mesothelioma, Malignant ; *Pleural Neoplasms/pathology ; Tumor Suppressor Proteins/genetics ; Ubiquitin Thiolesterase/genetics ; }, abstract = {OBJECTIVE: To assess the utility of BRCA1-associated protein 1 (BAP1) immunohistochemistry (IHC) for the diagnosis of malignant pleural mesothelioma (MPM) in fluid samples with atypical cytology.

METHODS: Pleural fluid samples with an atypical mesothelial proliferation (diagnostic categories: 'atypical' and 'suspicious') received between January 2015 and March 2018 at a tertiary referral centre were identified. Results of routine IHC testing were recorded for each case. BAP1 by IHC was performed and a final diagnosis sought from subsequent pathology specimens, medical records, or consensus clinical diagnosis.

RESULTS: Of 50 cases identified, 41 were reported as atypical and 9 as suspicious. Seven (14%) demonstrated loss of BAP1 staining, 40 retained BAP1 staining, 1 had heterogeneous staining, and 2 had insufficient cells for analysis. All seven cases with BAP1 loss were diagnosed with MPM on follow-up. Of those with retained BAP1, 52.5% (21) were subsequently diagnosed with MPM, while 40% (16) had non-MPM diagnoses after a median follow-up of 24 months. Three cases were not further investigated based on patient and clinician decision. The case with heterogeneous staining was diagnosed as mesothelioma by clinical consensus.

CONCLUSIONS: BAP1 IHC loss is highly specific for malignancy and has value as a rule-in test. Even in a tertiary centre with clinical interest in the cytological diagnosis of MPM this investigation was able to increase diagnostic accuracy beyond routine IHC studies. Cytological criteria remain valuable, as retained BAP1 in an atypical or suspicious mesothelial proliferation cannot exclude malignancy.}, } @article {pmid34012597, year = {2021}, author = {Schumann, SO and Kocher, G and Minervini, F}, title = {Epidemiology, diagnosis and treatment of the malignant pleural mesothelioma, a narrative review of literature.}, journal = {Journal of thoracic disease}, volume = {13}, number = {4}, pages = {2510-2523}, pmid = {34012597}, issn = {2072-1439}, abstract = {The malignant pleural mesothelioma is a very aggressive tumor which is arising from mesothelial cells and is associated with asbestos exposure. It is a heterogeneous cancer that shows a complex pattern of molecular changes, including genetic, chromosomic, and epigenetic abnormalities. The malignant pleural mesothelioma is characterized by a silent and slow clinical progression with an average period of 20-40 years from the asbestos exposure phase to the start of the symptoms. Unfortunately, to date, the therapeutic options are very limited, especially if the tumor is detected late. This narrative review provides an extended overview of the present evidence in the literature regarding the epidemiology, diagnostic pathways and treatment approaches of the malignant pleural mesothelioma. The treatment of mesothelioma has evolved slowly over the last 20 years not only from a surgical point of view but also radiotherapy, chemotherapy and immunotherapy play nowadays a key role. Several surgical strategies are available ranging from extrapleural pneumonectomy to cytoreductive surgery but a multidisciplinary approach seems to be mandatory because a single approach has not proved to date to be resolutive. New non-surgical treatment options appear to be promising but the results have to be taken in account with caution because clear evidence with high-quality studies is still lacking.}, } @article {pmid34008015, year = {2021}, author = {Cheung, M and Kadariya, Y and Sementino, E and Hall, MJ and Cozzi, I and Ascoli, V and Ohar, JA and Testa, JR}, title = {Novel LRRK2 mutations and other rare, non-BAP1-related candidate tumor predisposition gene variants in high-risk cancer families with mesothelioma and other tumors.}, journal = {Human molecular genetics}, volume = {30}, number = {18}, pages = {1750-1761}, pmid = {34008015}, issn = {1460-2083}, support = {P30 CA006927/CA/NCI NIH HHS/United States ; R01 CA148805/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; *Genetic Predisposition to Disease ; Humans ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/*genetics ; Male ; Mesothelioma, Malignant/*genetics ; Risk Factors ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {There is irrefutable evidence that germline BRCA1-associated protein 1 gene (BAP1) mutations contribute to malignant mesothelioma (MM) susceptibility. However, BAP1 mutations are not found in all cases with evidence of familial MM or in other high-risk cancer families affected by various cancers, including MM. The goal of this study was to use whole genome sequencing (WGS) to determine the frequency and types of germline gene variants occurring in 12 MM patients who were selected from a series of 141 asbestos-exposed MM patients with a family history of cancer but without a germline BAP1 mutation. WGS was also performed on two MM cases, a proband and sibling, from a previously reported family with multiple cases of MM without the inheritance of a predisposing BAP1 mutation. Altogether, germline DNA sequencing variants were identified in 21 cancer-related genes in 10 of the 13 probands. Germline indel, splice site and missense mutations and two large deletions were identified. Among the 13 MM index cases, 6 (46%) exhibited one or more predicted pathogenic mutations. Affected genes encode proteins involved in DNA repair (ATM, ATR, BRCA2, BRIP1, CHEK2, MLH3, MUTYH, POLE, POLE4, POLQ and XRCC1), chromatin modification (ARID1B, DNMT3A, JARID2 and SETD1B) or other cellular pathways: leucine-rich repeat kinase 2 gene (LRRK2) (two cases) and MSH4. Notably, somatic truncating mutation or deletions of LRRK2 were occasionally found in MMs in The Cancer Genome Atlas, and the expression of LRRK2 was undetectable or downregulated in a majority of primary MMs and MM cell lines we examined, implying that loss of LRRK2 expression is a newly recognized tumor suppressor alteration in MM.}, } @article {pmid34000787, year = {2021}, author = {Wilk, E and Krówczyńska, M}, title = {Malignant mesothelioma and asbestos exposure in Europe: Evidence of spatial clustering.}, journal = {Geospatial health}, volume = {16}, number = {1}, pages = {}, doi = {10.4081/gh.2021.951}, pmid = {34000787}, issn = {1970-7096}, mesh = {Aged ; *Asbestos ; Cluster Analysis ; Europe/epidemiology ; Female ; Humans ; *Lung Neoplasms/epidemiology ; Male ; *Mesothelioma/epidemiology ; *Mesothelioma, Malignant ; Spatial Analysis ; Switzerland ; }, abstract = {Exposure to asbestos causes a wide range of diseases, such as asbestosis, malignant mesothelioma (MM) and other types of cancer. Many European countries have reduced production and use of asbestos and some have banned it altogether. Based on data derived from the World Health Organisation (WHO) Cancer Mortality Database, we investigated whether some regions in Europe could have a higher relative risk of MM incidence than others. The data were compared, including the number of MM deaths per million inhabitants and aged-standardized mortality rates. Applying Moran's I and Getis-Ord Gi statistic on the agedstandardized mortality rates of MM cases assisted the spatial analysis of the occurrence of health events leading to an assessment of the heterogeneity of distribution and cluster detection of MM. We found a statistically significant positive autocorrelation for the male population and also the general population, while there was no statistically significant positive one for the female population. Hotspots of relative risk of developing MM were found in northwestern Europe. For the general population, Great Britain and the Netherlands stood out with high levels at the 99% and 95% confidence levels, respectively. For the male population, the results were similar, but with addition of risk also in Belgium and Switzerland. However, in many European countries with high asbestos use per capita, the MM incidence was found to still be low. The reasons for this are not yet clear, but part of the problem is certainly due to incomplete data in registers and databases. The latency time can be longer than 40 years and is related to the intensity and time of exposure (occupational, para-occupational and environmental). In Europe, even though peak production occurred in the 1960s and 1970s, a significant decrease in production did not occur until 25 years later, which means that the impact will continue for as late as The mid 2030s.}, } @article {pmid33998299, year = {2021}, author = {Tanrıverdi, Z and Meteroglu, F and Yüce, H and Şenyiğit, A and Işcan, M and Unüvar, S}, title = {The usefulness of biomarkers in diagnosis of asbestos-induced malignant pleural mesothelioma.}, journal = {Human & experimental toxicology}, volume = {40}, number = {11}, pages = {1817-1824}, doi = {10.1177/09603271211017324}, pmid = {33998299}, issn = {1477-0903}, mesh = {Adult ; Asbestos/*toxicity ; Biomarkers, Tumor/blood ; Cell Adhesion Molecules/*blood ; Chitinase-3-Like Protein 1/*blood ; Cross-Sectional Studies ; Female ; Humans ; Indoleamine-Pyrrole 2,3,-Dioxygenase/*blood ; Male ; Mesothelioma, Malignant/blood/*chemically induced/*diagnosis/physiopathology ; Middle Aged ; Neopterin/*blood ; Pleural Neoplasms/chemically induced/diagnosis/physiopathology ; Prospective Studies ; Tenascin/*blood ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is a malignant tumor that is associated mostly with asbestos exposure. The present study was to evaluates the diagnostic value of neopterin, periostin, YKL-40, Tenascin-C (TNC), and Indolamine 2,3-dioxygenase (IDO) as noninvasive markers of malign pleural mesothelioma.

METHODS: Included in the study were 30 patients diagnosed with malign pleural mesothelioma, and 25 people as a control group. Biomarker levels were determined using an enzyme immunoassay . A Mann-Whitney U test and Spearman correlation methods were used for the statistical analysis.

RESULTS: All evaluated biomarkers were found to be significantly higher in the MPM group than in the control group (p < 0.05). There was no effect of such variables as gender, age or MPMsubtype on the parameters (p > 0.05) in the patient group. All biomarkers were positively correlated with each other (p < 0.001).

CONCLUSIONS: The current non-invasive biomarkers that can be used in the diagnosis of MPM yielded significant results and can make important contributions to the early diagnosis of MPM.}, } @article {pmid33971174, year = {2022}, author = {Zhou, N and Rice, DC and Tsao, AS and Lee, PP and Haymaker, CL and Corsini, EM and Antonoff, MB and Hofstetter, WL and Rajaram, R and Roth, JA and Swisher, SG and Vaporciyan, AA and Walsh, GL and Mehran, RJ and Sepesi, B}, title = {Extrapleural Pneumonectomy Versus Pleurectomy/Decortication for Malignant Pleural Mesothelioma.}, journal = {The Annals of thoracic surgery}, volume = {113}, number = {1}, pages = {200-208}, doi = {10.1016/j.athoracsur.2021.04.078}, pmid = {33971174}, issn = {1552-6259}, mesh = {Aged ; Female ; Humans ; Male ; Mesothelioma, Malignant/mortality/*surgery ; Middle Aged ; Pleura/*surgery ; Pleural Neoplasms/mortality/*surgery ; Pneumonectomy/*methods ; Postoperative Complications/epidemiology ; Retrospective Studies ; Survival Rate ; Time Factors ; }, abstract = {BACKGROUND: Whether extrapleural pneumonectomy (EPP) or extended pleurectomy/decortication (P/D) is the optimal resection for malignant pleural mesothelioma remains controversial. We therefore compared perioperative outcomes and long-term survival of patients who underwent EPP versus P/D.

METHODS: Patients with the diagnosis of malignant pleural mesothelioma who underwent either EPP or P/D from 2000 to 2019 were identified from our departmental database. Propensity score matching was performed to minimize potential confounders for EPP or P/D. Survival analysis was performed by the Kaplan-Meier method and Cox multivariable analysis.

RESULTS: Of 282 patients, 187 (66%) underwent EPP and 95 (34%) P/D. Even with propensity score matching, perioperative mortality was significantly higher for EPP than for P/D (11% vs 0%; P = .031); when adjusted for perioperative mortality, median overall survival between EPP and P/D was 15 versus 22 months, respectively (P = .276). Cox multivariable analysis for the matched cohort identified epithelioid histology (hazard ratio [HR], 0.56; P = .029), macroscopic complete resection (HR, 0.41; P = .004), adjuvant radiation therapy (HR, 0.57; P = .019), and more recent operative years (HR, 0.93; P = .011)-but not P/D-to be associated with better survival. Asbestos exposure (HR, 2.35; P = .003) and pathologic nodal disease (HR, 1.61; P = .048) were associated with worse survival.

CONCLUSIONS: In a multimodality treatment setting, P/D and EPP had comparable long-term oncologic outcomes, although P/D had much lower perioperative mortality. The goal of surgical cytoreduction should be macroscopic complete resection achieved by the safest operation a patient can tolerate.}, } @article {pmid33959504, year = {2021}, author = {Arrieta, O and Muñoz-Montaño, W and Muñiz-Hernández, S and Campos, S and Catalán, R and Soto-Molina, H and Guzmán Vázquez, S and Díaz-Álvarez, O and Martínez-Pacheco, V and Turcott, JG and Ramos-Ramírez, M and Cabrera-Miranda, L and Barrón, F and Cardona, AF}, title = {Efficacy, Safety, and Cost-Minimization Analysis of Continuous Infusion of Low-Dose Gemcitabine Plus Cisplatin in Patients With Unresectable Malignant Pleural Mesothelioma.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {641975}, pmid = {33959504}, issn = {2234-943X}, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is rare and aggressive neoplasia, with a poor prognosis; furthermore, the monetary cost of its treatment represents a major challenge for many patients. The economic burden this malignancy imposes is underscored by the fact that asbestos exposure, which is the most frequent risk factor, is much more prevalent in the lower socioeconomic population of developing countries. The aims of the present study were to evaluate the efficacy, safety, and cost of continuous infusion of low-dose Gemcitabine plus Cisplatin (CIGC) as a treatment strategy for patients with unresectable MPM.

METHODS: We performed a prospective cohort study to determine efficacy and safety of continuous infusion gemcitabine at a dose of 250 mg/m2 in a 6-h continuous infusion plus cisplatin 35 mg/m2 on days 1 and 8 of a 21-day cycle in patients with unresectable MPM. We also performed a cost-minimization analysis to determine if this chemotherapy regimen is less expensive than other currently used regimens.

RESULTS: The median number of chemotherapy cycles was six (range 1-11 cycles); objective response rate was documented in 46.2%, and disease control rate was seen in 81.2%. Median PFS was 8.05 months (CI 95% 6.97-9.13); median OS was 16.16 months (CI 95% 12.5-19.9). The cost minimization analysis revealed savings of 66.4, 61.9, and 97.7% comparing CIGC with short-infusion gemcitabine plus cisplatin (SIGC), cisplatin plus pemetrexed (CP), and cisplatin plus pemetrexed and bevacizumab (CPB), respectively. Furthermore, this chemotherapy regimen proved to be safe at the administered dosage.

CONCLUSION: CIGC is an effective and safe treatment option for patients with unresectable MPM; besides, this combination is a cost-saving option when compared with other frequently used chemotherapy schemes. Therefore, this treatment scheme should be strongly considered for patients with unresectable MPM and limited economic resources.}, } @article {pmid33952230, year = {2021}, author = {Gray, SG}, title = {Emerging avenues in immunotherapy for the management of malignant pleural mesothelioma.}, journal = {BMC pulmonary medicine}, volume = {21}, number = {1}, pages = {148}, pmid = {33952230}, issn = {1471-2466}, mesh = {Antineoplastic Agents/*therapeutic use ; CTLA-4 Antigen/antagonists & inhibitors ; Clinical Trials as Topic ; Combined Modality Therapy ; Humans ; Immunotherapy ; Lung Neoplasms/*therapy ; Mesothelioma, Malignant/*therapy ; Pleural Neoplasms/*therapy ; Programmed Cell Death 1 Ligand 2 Protein/antagonists & inhibitors ; Programmed Cell Death 1 Receptor/antagonists & inhibitors ; }, abstract = {BACKGROUND: The role of immunotherapy in cancer is now well-established, and therapeutic options such as checkpoint inhibitors are increasingly being approved in many cancers such as non-small cell lung cancer (NSCLC). Malignant pleural mesothelioma (MPM) is a rare orphan disease associated with prior exposure to asbestos, with a dismal prognosis. Evidence from clinical trials of checkpoint inhibitors in this rare disease, suggest that such therapies may play a role as a treatment option for a proportion of patients with this cancer.

MAIN TEXT: While the majority of studies currently focus on the established checkpoint inhibitors (CTLA4 and PD1/PDL1), there are many other potential checkpoints that could also be targeted. In this review I provide a synopsis of current clinical trials of immunotherapies in MPM, explore potential candidate new avenues that may become future targets for immunotherapy and discuss aspects of immunotherapy that may affect the clinical outcomes of such therapies in this cancer.

CONCLUSIONS: The current situation regarding checkpoint inhibitors in the management of MPM whilst encouraging, despite impressive durable responses, immune checkpoint inhibitors do not provide a long-term benefit to the majority of patients with cancer. Additional studies are therefore required to further delineate and improve our understanding of both checkpoint inhibitors and the immune system in MPM. Moreover, many new potential checkpoints have yet to be studied for their therapeutic potential in MPM. All these plus the existing checkpoint inhibitors will require the development of new biomarkers for patient stratification, response and also for predicting or monitoring the emergence of resistance to these agents in MPM patients. Other potential therapeutic avenues such CAR-T therapy or treatments like oncolytic viruses or agents that target the interferon pathway designed to recruit more immune cells to the tumor also hold great promise in this hard to treat cancer.}, } @article {pmid33946118, year = {2021}, author = {Aigner, C and Brüning, T and Eberhardt, WEE and Härter, M and Kaelberlah, HP and Metzenmacher, M and Shah, R and Taube, C and Thomas, M}, title = {[The Current Therapy of Asbestos-Associated Malignant Pleural Mesothelioma - An Expert Consensus Paper].}, journal = {Pneumologie (Stuttgart, Germany)}, volume = {75}, number = {10}, pages = {776-794}, pmid = {33946118}, issn = {1438-8790}, mesh = {*Asbestos/adverse effects ; Consensus ; Humans ; *Lung Neoplasms/diagnosis/therapy ; *Mesothelioma/diagnosis/therapy ; *Mesothelioma, Malignant ; *Occupational Exposure ; *Pleural Neoplasms/diagnosis/therapy ; }, abstract = {Asbestos-related mesotheliomas belong to the group of the most frequent occupational diseases in Germany, reaching about 1,000 new cases per year. The disease has a dismal prognosis because most tumors remain asymptomatic for a long time and therefore are diagnosed as incidental findings at later stages.During the last decade the German Social Accident Insurance (DGUV) has made considerable efforts to prepone the diagnosis in order to detect the disease at earliest possible stages. These efforts resulted in new findings showing that, in a high-risk group, a combination of the biomarkers calretinin and mesothelin was able to advance the diagnosis up to 12 months.Ideally, the diagnosis of a mesothelioma at an early stage has to be accompanied by the best possible individualized therapy. Standard therapeutic strategies are surgery and chemotherapy, added by radiotherapy and psycho-oncology. In recent years, several new therapeutic avenues are being explored. This review comprehensively presents both old and new therapeutic options in mesothelioma, based on international Leitlinien and new studies.}, } @article {pmid33945895, year = {2021}, author = {Ejegi-Memeh, S and Robertson, S and Taylor, B and Darlison, L and Tod, A}, title = {Gender and the experiences of living with mesothelioma: A thematic analysis.}, journal = {European journal of oncology nursing : the official journal of European Oncology Nursing Society}, volume = {52}, number = {}, pages = {101966}, doi = {10.1016/j.ejon.2021.101966}, pmid = {33945895}, issn = {1532-2122}, mesh = {Female ; Humans ; Male ; Men ; *Mesothelioma/therapy ; *Mesothelioma, Malignant ; Qualitative Research ; }, abstract = {PURPOSE: Mesothelioma is a terminal cancer caused by exposure to asbestos. As a cancer with a higher rate in men than women, women's experiences of living with mesothelioma are often underexplored. Furthermore, men's experiences are often taken for granted and therefore have remained underexplored. This paper considers men's and women's experiences across the mesothelioma pathway.

METHODS: This qualitative study incorporated semi-structured interviews with 13 men and 11 women living with mesothelioma. Telephone interviews took place between July and December 2019, and were audio recorded, transcribed and anonymised. Thematic analysis was used to analyse the data.

RESULTS: Three themes were developed in relation to the gendered experience of mesothelioma: familial responsibility and social perceptions; support preferences; and treatment and trials. Analysis suggests that men and women's sense of familial responsibility varied. Differences in priorities and motivations influenced approaches to seeking support, compensation and, making decisions around treatments and clinical trials.

CONCLUSIONS: The current study reports on how gender can influence the experience of living with mesothelioma. The findings indicate how the patients' role in their families and society can more broadly influence their experiences, choices and preferences. Nurses caring for mesothelioma patients need high quality research on which to base their practice. Recognition and an understanding of the underlyingfactors influencing patients' decision-making will enable nurses and other professionals to support their patients better.}, } @article {pmid33945357, year = {2021}, author = {Davis, AP and Kao, SC and Clarke, SJ and Boyer, M and Pavlakis, N}, title = {Emerging biological therapies for the treatment of malignant pleural mesothelioma.}, journal = {Expert opinion on emerging drugs}, volume = {26}, number = {2}, pages = {179-192}, doi = {10.1080/14728214.2021.1924670}, pmid = {33945357}, issn = {1744-7623}, mesh = {Biological Therapy/methods ; Biomarkers, Tumor/metabolism ; Humans ; Immunotherapy/*methods ; Mesothelioma, Malignant/immunology/*therapy ; Pleural Neoplasms/immunology/*therapy ; Precision Medicine ; }, abstract = {Introduction: Malignant pleural mesothelioma (MPM) has limited treatment options with minimal new therapy approvals for unresectable disease in the past 15 years. However, considerable work has occurred to develop immunotherapies and biomarker driven therapy to improve patient outcomes over this period.Areas covered: This review examines current standard of care systemic therapy in the first- and second line setting. The last 12 months has seen 2 significant trials (Checkmate 743 and CONFIRM) which provide evidence supporting the role of immunotherapy in the management of MPM. Further trials are underway to assess the role of combination chemoimmunotherapy and personalized therapy. Additionally, a large number of clinical trials are ongoing to assess the efficacy of oncoviral, dendritic cell, anti-mesothelin and chimeric antigen receptor T cell therapy in the treatment of MPM.Expert opinion: Recent Phase III trial results have established a role for immunotherapy in the management of MPM. The optimal sequencing and combination of chemotherapy and immunotherapy remains to be determined. Novel therapies for MPM are promising however efficacy remains to be determined and issues remain regarding access to and delivery of these therapies.}, } @article {pmid33927865, year = {2021}, author = {Muralidhar, V}, title = {An unusual presentation of acute abdomen: infarcted peritoneal cyst-a probable asbestos-related benign cystic mesothelioma.}, journal = {Journal of surgical case reports}, volume = {2021}, number = {4}, pages = {rjab129}, pmid = {33927865}, issn = {2042-8812}, abstract = {This is a report of a rare case of an infarcted pelvic intra-abdominal cyst, having no mesenteric connection presenting as an acute abdomen. The patient had significant asbestos exposure. The cyst was treated successfully by surgical excision. Histopathology showed an infarcted cyst; the lining was destroyed, precluding marker studies. A diagnosis of benign cystic peritoneal mesothelioma (BCPM) was made by excluding other causes of solitary pelvic intra-abdominal cysts. BCPM has been classified as an asbestos-related neoplasm and is usually seen in the pelvis adjunct to the urinary bladder. One-year post-surgery, there was no recurrence. The case report shows that infarcted pelvic mesothelial cysts can present as an acute abdomen and can be treated successfully by total excision with no recurrence.}, } @article {pmid33917061, year = {2021}, author = {Brcic, L and Mathilakathu, A and Walter, RFH and Wessolly, M and Mairinger, E and Beckert, H and Kreidt, D and Steinborn, J and Hager, T and Christoph, DC and Kollmeier, J and Mairinger, T and Wohlschlaeger, J and Schmid, KW and Borchert, S and Mairinger, FD}, title = {Digital Gene Expression Analysis of Epithelioid and Sarcomatoid Mesothelioma Reveals Differences in Immunogenicity.}, journal = {Cancers}, volume = {13}, number = {8}, pages = {}, pmid = {33917061}, issn = {2072-6694}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive malignancy associated with asbestos exposure. Median survival ranges from 14 to 20 months after initial diagnosis. As of November 2020, the FDA approved a combination of immune checkpoint inhibitors after promising intermediate results. Nonetheless, responses remain unsatisfying. Adequate patient stratification to improve response rates is still lacking. This retrospective study analyzed formalin fixed paraffin embedded specimens from a cohort of 22 MPM. Twelve of those samples showed sarcomatoid, ten epithelioid differentiation. Complete follow-up, including radiological assessment of response by modRECIST and time to death, was available with reported deaths of all patients. RNA of all samples was isolated and subjected to digital gene expression pattern analysis. Our study revealed a notable difference between epithelioid and sarcomatoid mesothelioma, showing differential gene expression for 304/698 expressed genes. Whereas antigen processing and presentation to resident cytotoxic T cells as well as phagocytosis is highly affected in sarcomatoid mesothelioma, cell-cell interaction via cytokines seems to be of greater importance in epithelioid cases. Our work reveals the specific role of the immune system within the different histologic subtypes of MPM, providing a more detailed background of their immunogenic potential. This is of great interest regarding therapeutic strategies including immunotherapy in mesothelioma.}, } @article {pmid33910295, year = {2021}, author = {Li, N and Wang, D and Chen, ZJ and Mao, WM}, title = {[Asbestos-induced malignant peritoneal mesothelioma complicated with lung cancer:a case report].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {39}, number = {4}, pages = {305-307}, doi = {10.3760/cma.j.cn121094-20200114-00029}, pmid = {33910295}, issn = {1001-9391}, support = {81672315//National Natural Science Foundation of China/ ; }, mesh = {*Asbestos/adverse effects ; Humans ; *Lung Neoplasms ; *Mesothelioma ; *Mesothelioma, Malignant ; *Occupational Exposure/adverse effects ; *Peritoneal Neoplasms ; }, abstract = {Asbestos is harmful to human, and populations with occupational and environmental exposure to respirable asbestos fibers have higher risk of cancers like malignant mesothelioma and lung cancer. At present, patient with asbestos-induced malignant peritoneal mesothelioma and lung cancer is rare. In this study, we analyzed the clinical data of a case of asbestos-induced malignant peritoneal mesothelioma complicated with lung cancer to investigate the diagnosis and treatment of this disease.}, } @article {pmid33890321, year = {2021}, author = {Zhang, F and Yuan, X and Sun, H and Yin, X and Gao, Y and Zhang, M and Jia, Z and Yu, M and Ying, S and Xia, H and Ju, L and Xiao, Y and Tao, H and Lou, J and Zhu, L}, title = {A nontoxic dose of chrysotile can malignantly transform Met-5A cells, in which microRNA-28 has inhibitory effects.}, journal = {Journal of applied toxicology : JAT}, volume = {41}, number = {11}, pages = {1879-1892}, doi = {10.1002/jat.4174}, pmid = {33890321}, issn = {1099-1263}, mesh = {Asbestos, Serpentine/*toxicity ; Cells, Cultured ; Dose-Response Relationship, Drug ; Humans ; MicroRNAs/*metabolism ; }, abstract = {Chrysotile, which is classified as a class I carcinogen by the International Agency for Research on Cancer (IARC), has extensive application in the industry and can lead to lung or other cancers. However, whether chrysotile causes malignant mesothelioma and its molecular mechanism remain debatable. Thus, this study aimed to demonstrate the mesothelioma-inducing potential of chrysotile at the mesothelial cellular level and the function of microRNA-28 in malignantly transformed mesothelial MeT-5A cells. MeT-5A cells malignantly transformed by a nontoxic dose of chrysotile were named Asb-T, and miR-28 expression was downregulated in Asb-T cells. Restoration of miR-28 expression inhibited the proliferation, migration and invasion of Asb-T cells. We verified that IMPDH is a putative target of miR-28. The expression of IMPDH was significantly higher in Asb-T MeT-5A cells than in control cells, whereas the opposite trend was observed with miR-28 overexpression. Additionally, inhibition of IMPDH had similar effects as miR-28 overexpression. After miR-28 was elevated or IMPDH was inhibited, Ras activation was reduced, and its downstream pathways (the Erk and Akt signalling pathways) were inhibited. Surprisingly, the content of miR-28 in the blood of mesothelioma patients was higher than that in control subjects. Overall, nontoxic doses of chrysotile can cause malignant transformation of MeT-5A cells. Moreover, miR-28 inhibits the proliferation, migration and invasion of Asb-T MeT-5A cells, negatively regulates the expression of IMPDH through the Ras signalling pathway and may be an important therapeutic target.}, } @article {pmid33889258, year = {2021}, author = {Ouafki, I and Nouiakh, L and Boujarnija, R and Amarti, A and Amaadour, L and Oualla, K and Benbrahim, Z and Arifi, S and Mellas, N}, title = {[Malignant mesothelioma of the ovary: a case report].}, journal = {The Pan African medical journal}, volume = {38}, number = {}, pages = {92}, pmid = {33889258}, issn = {1937-8688}, mesh = {Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Humans ; Mesothelioma, Malignant/*diagnosis/pathology/therapy ; Middle Aged ; Neoplasm Staging ; Ovarian Neoplasms/*diagnosis/pathology/therapy ; Tomography, X-Ray Computed ; }, abstract = {Primary malignant mesothelioma of the ovary (PMMO) is an extremely rare tumor which can develop from mesothelial cells. This neoplasia is caused predominantly by exposure to asbestos or other cancer-causing agents. Preoperative assessment, based on computed tomography (CT) scan, magnetic resonance imaging and positron emission tomography, is essential for cancer staging. Anatomopathological diagnosis is based on immunohistochemical findings. PMMO is an exceptional disease involving a multidisciplinary therapeutic strategy including the use of chemotherapy which improves the management and prognosis of patients. This study reports the case of a female patient undergoing suboptimal surgery complemented by adjuvant chemotherapy with complete radiological response and 1-year disease-free survival.}, } @article {pmid33874885, year = {2021}, author = {Kumagai-Takei, N and Nishimura, Y and Matsuzaki, H and Lee, S and Yoshitome, K and Ito, T and Otsuki, T}, title = {Effect of IL-15 addition on asbestos-induced suppression of human cytotoxic T lymphocyte induction.}, journal = {Environmental health and preventive medicine}, volume = {26}, number = {1}, pages = {50}, pmid = {33874885}, issn = {1347-4715}, support = {16K09114//Japan Society for the Promotion of Science/ ; 27B068//Kawasaki Medical School/ ; 28B008//Kawasaki Medical School/ ; }, mesh = {Asbestos/*adverse effects ; CD8-Positive T-Lymphocytes/cytology/drug effects/*immunology/metabolism ; Humans ; Interleukin-15/*pharmacology ; Lymphocyte Activation/*drug effects/immunology ; T-Lymphocytes, Cytotoxic/cytology/drug effects/*immunology/metabolism ; }, abstract = {BACKGROUND: Asbestos fibers possess tumorigenicity and are thought to cause mesothelioma. We have previously reported that exposure to asbestos fibers causes a reduction in antitumor immunity. Asbestos exposure in the mixed lymphocyte reaction (MLR) showed suppressed induction of cytotoxic T lymphocytes (CTLs), accompanied by a decrease in proliferation of CD8[+] T cells. Recently, we reported that asbestos-induced suppression of CTL induction is not due to insufficient levels of interleukin-2 (IL-2). In this study, we continue to investigate the mechanism responsible for the effect of asbestos fibers on the differentiation of CTLs and focus on interleukin-15 (IL-15) which is known to be a regulator of T lymphocyte proliferation.

METHODS: For MLR, human peripheral blood mononuclear cells (PBMCs) were cultured with irradiated allogenic PBMCs upon exposure to chrysotile B asbestos at 5 μg/ml for 7 days. After 2 days of culture, IL-15 was added at 1 ng/ml. After 7 days of MLR, PBMCs were collected and analyzed for phenotypic and functional markers of CD8[+] T cells with fluorescence-labeled anti-CD3, anti-CD8, anti-CD45RA, anti-CD45RO, anti-CD25, and anti-granzyme B antibodies using flow cytometry. To examine the effect of IL-15 on the expression level of intracellular granzyme B in proliferating and non-proliferating CD8[+] lymphocytes, PBMCs were stained using carboxyfluorescein diacetate succinimidyl ester (CFSE) and then washed and used for the MLR.

RESULTS: IL-15 addition partially reversed the decrease in CD3[+]CD8[+] cell numbers and facilitated complete recovery of granzyme B[+] cell percentages. IL-15 completely reversed the asbestos-induced decrease in percentage of granzyme B[+] cells in both non-proliferating CFSE-positive and proliferating CFSE-negative CD8[+] cells. The asbestos-induced decrease in the percentage of CD25[+] and CD45RO[+] cells in CD8[+] lymphocytes was not reversed by IL-15.

CONCLUSION: These findings indicate that CTLs induced upon exposure to asbestos possess dysfunctional machinery that can be partly compensated by IL-15 supplementation, and that IL-15 is more effective in the recovery of proliferation and granzyme B levels from asbestos-induced suppression of CTL induction compared with IL-2.}, } @article {pmid33872411, year = {2021}, author = {Ezeka, G and Adhikary, G and Kandasamy, S and Friedberg, JS and Eckert, RL}, title = {Sulforaphane inhibits PRMT5 and MEP50 function to suppress the mesothelioma cancer cell phenotype.}, journal = {Molecular carcinogenesis}, volume = {60}, number = {7}, pages = {429-439}, pmid = {33872411}, issn = {1098-2744}, support = {R01 CA211909/CA/NCI NIH HHS/United States ; R25 GM055036/GM/NIGMS NIH HHS/United States ; }, mesh = {Adaptor Proteins, Signal Transducing/genetics/*metabolism ; Animals ; Anticarcinogenic Agents/pharmacology ; Gene Expression Regulation, Neoplastic/drug effects ; Histones/metabolism ; Humans ; Isothiocyanates/*pharmacology ; Mesothelioma/*drug therapy/metabolism/*pathology ; Mice, Inbred NOD ; Phenotype ; Protein-Arginine N-Methyltransferases/genetics/*metabolism ; Signal Transduction/drug effects ; Sulfoxides/*pharmacology ; Tumor Cells, Cultured ; Xenograft Model Antitumor Assays ; Mice ; }, abstract = {Mesothelioma is a highly aggressive cancer of the mesothelial lining that is caused by exposure to asbestos. Surgical resection followed by chemotherapy is the current treatment strategy, but this is marginally successful and leads to drug-resistant disease. We are interested in factors that maintain the aggressive mesothelioma cancer phenotype as therapy targets. Protein arginine methyltransferase 5 (PRMT5) functions in concert with the methylosome protein 50 (MEP50) cofactor to catalyze symmetric dimethylation of key arginine resides in histones 3 and 4 which modifies the chromatin environment to alter tumor suppressor and oncogene expression and enhance cancer cell survival. Our studies show that PRMT5 or MEP50 loss reduces H4R3me2s formation and that this is associated with reduced cancer cell spheroid formation, invasion, and migration. Treatment with sulforaphane (SFN), a diet-derived anticancer agent, reduces PRMT5/MEP50 level and H4R3me2s formation and suppresses the cancer phenotype. We further show that SFN treatment reduces PRMT5 and MEP50 levels and that this reduction is required for SFN suppression of the cancer phenotype. SFN treatment also reduces tumor formation which is associated with reduced PRMT5/MEP50 expression and activity. These findings suggest that SFN may be a useful mesothelioma treatment agent that operates, at least in part, via suppression of PRMT5/MEP50 function.}, } @article {pmid33851620, year = {2021}, author = {Fujishima, F and Konosu-Fukaya, S and Nabeshima, K and McNamara, KM and Sakamoto, K and Sakurada, J and Sasano, H and Nakamura, Y}, title = {Histological and immunohistochemical characteristics and p16 status studied by FISH in six incidentally detected cases of well-differentiated papillary mesothelioma of the peritoneum.}, journal = {Indian journal of pathology & microbiology}, volume = {64}, number = {2}, pages = {277-281}, doi = {10.4103/IJPM.IJPM_111_20}, pmid = {33851620}, issn = {0974-5130}, mesh = {Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Biomarkers, Tumor/metabolism ; Cyclin-Dependent Kinase Inhibitor p16/genetics/*metabolism ; Female ; Humans ; Immunohistochemistry/methods ; In Situ Hybridization, Fluorescence ; Male ; Mesothelioma/diagnosis/*pathology/surgery ; Middle Aged ; Peritoneal Neoplasms/diagnosis/*pathology/surgery ; Peritoneum/pathology ; Tumor Suppressor Proteins/metabolism ; Ubiquitin Thiolesterase/metabolism ; }, abstract = {Well-differentiated papillary mesothelioma (WDPM) is an uncommon mesothelial neoplasm, which is generally regarded as benign or indolent in terms of its clinical behavior. However, details about WDPM have remained relatively unknown. Therefore, in this study, we examined six incidentally detected cases of WDPM of the peritoneum. All six cases were surgically excised, without any additional therapeutic measures. None of the cases showed recurrence. All six cases presented single lesions and the tumor sizes ranged from 2 to 10 mm. Histologically, all six cases exhibited papillary proliferation of cytologically bland mesothelial cells with a fibroconnective tissue core. One of the cases (Case 6) presented small invasive foci in the stalk. The tumor cells were immunohistochemically positive for mesothelial markers and negative for GLUT-1, p53, and CD146. The Ki-67 labeling index of the tumor cells was lower than 5% at the hot spots. All samples were BAP1-positive. None of the samples presented p16 homozygous deletion, as assessed by fluorescence in situ hybridization (FISH). None of the patients deceased due to WDPM. However, in Case 3, death occurred due to pancreatic cancer. The results of this study indicate the importance of analyzing immunohistochemical markers and p16 status to diagnose WDPM accurately.}, } @article {pmid33834530, year = {2021}, author = {DeBono, NL and Warden, H and Logar-Henderson, C and Shakik, S and Dakouo, M and MacLeod, J and Demers, PA}, title = {Incidence of mesothelioma and asbestosis by occupation in a diverse workforce.}, journal = {American journal of industrial medicine}, volume = {64}, number = {6}, pages = {476-487}, doi = {10.1002/ajim.23245}, pmid = {33834530}, issn = {1097-0274}, mesh = {Aged ; Asbestosis/*epidemiology ; Female ; Humans ; Incidence ; Industry/statistics & numerical data ; Lung Neoplasms/epidemiology ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Occupational Diseases/*epidemiology ; Occupations/*statistics & numerical data ; Ontario/epidemiology ; *Population Surveillance ; Proportional Hazards Models ; Registries ; Workers' Compensation/statistics & numerical data ; Workforce/statistics & numerical data ; }, abstract = {OBJECTIVE: We sought to characterize detailed patterns of mesothelioma and asbestosis incidence in the workforce as part of an occupational disease surveillance program in Ontario, Canada.

METHODS: The Occupational Disease Surveillance System (ODSS) cohort was established using workers' compensation claims data and includes 2.18 million workers employed from 1983 to 2014. Workers were followed for mesothelioma and asbestosis diagnoses in Ontario Cancer Registry, physician, hospital, and ambulatory care records through 2016. Trends in incidence rates were estimated over the study period. Cox proportional hazard models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs).

RESULTS: A total of 854 mesothelioma and 737 asbestosis cases were diagnosed during follow-up. Compared with all other workers in the ODSS, those employed in construction trades occupations had the greatest adjusted incidence rate of both mesothelioma (223 cases; HR, 2.38; 95% CI: 2.03-2.78) and asbestosis (261 cases; HR, 3.64; 95% CI: 3.11-4.25). Rates were particularly elevated for insulators, pipefitters and plumbers, and carpenters. Workers in welding and flame cutting, boiler making, and mechanic and machinery repair occupations, as well as those in industrial chemical and primary metal manufacturing industries, had strongly elevated rates of both diseases. Rates were greater than anticipated for workers in electrical utility occupations and education and related services.

CONCLUSIONS: Results substantiate the risk of mesothelioma and asbestosis in occupation and industry groups in the Ontario workforce with known or suspected asbestos exposure. Sustained efforts to prevent the occurrence of additional cases of disease in high-risk groups are warranted.}, } @article {pmid33816102, year = {2021}, author = {Mizuhashi, K and Okamoto, K and Kishimoto, T}, title = {A patient with epithelioid pleural mesothelioma (Myxoid variant) who survived for a long period without treatment.}, journal = {Respiratory medicine case reports}, volume = {33}, number = {}, pages = {101381}, pmid = {33816102}, issn = {2213-0071}, abstract = {Pleural mesothelioma is a disease with a very poor prognosis. Here, we report a mesothelioma patient who survived for 5 years and a half. As a result of the autopsy, the tumor was diagnosed as a myxoid variant, which is internationally proposed as a histological subtype of epithelioid mesothelioma with a relatively favorable prognosis. Since patients with this disease are expected to survive for a long period even without treatment, careful determination of the therapeutic approach is considered necessary. This report is considered to be the first of a myxoid variant epithelioid pleural mesothelioma in Japan.}, } @article {pmid33804168, year = {2021}, author = {Barbarino, M and Giordano, A}, title = {Assessment of the Carcinogenicity of Carbon Nanotubes in the Respiratory System.}, journal = {Cancers}, volume = {13}, number = {6}, pages = {}, pmid = {33804168}, issn = {2072-6694}, abstract = {In 2014, the International Agency for Research on Cancer (IARC) classified the first type of carbon nanotubes (CNTs) as possibly carcinogenic to humans, while in the case of other CNTs, it was not possible to ascertain their toxicity due to lack of evidence. Moreover, the physicochemical heterogeneity of this group of substances hamper any generalization on their toxicity. Here, we review the recent relevant toxicity studies produced after the IARC meeting in 2014 on an homogeneous group of CNTs, highlighting the molecular alterations that are relevant for the onset of mesothelioma. Methods: The literature was searched on PubMed and Web of Science for the period 2015-2020, using different combinations keywords. Only data on normal cells of the respiratory system after exposure to fully characterized CNTs for their physico-chemical characteristics were included. Recent studies indicate that CNTs induce a sustained inflammatory response, oxidative stress, fibrosis and histological alterations. The development of mesothelial hyperplasia, mesothelioma, and lungs tumors have been also described in vivo. The data support a strong inflammatory potential of CNTs, similar to that of asbestos, and provide evidence that CNTs exposure led to molecular alterations known to have a key role in mesothelioma onset. These evidences call for an urgent improvement of studies on exposed human populations and adequate systems for monitoring the health of workers exposed to this putative carcinogen.}, } @article {pmid33802313, year = {2021}, author = {Lettieri, S and Bortolotto, C and Agustoni, F and Lococo, F and Lancia, A and Comoli, P and Corsico, AG and Stella, GM}, title = {The Evolving Landscape of the Molecular Epidemiology of Malignant Pleural Mesothelioma.}, journal = {Journal of clinical medicine}, volume = {10}, number = {5}, pages = {}, pmid = {33802313}, issn = {2077-0383}, abstract = {Malignant pleural mesothelioma (MPM) is a rare and aggressive malignancy that most commonly affects the pleural lining of the lungs. It has a strong association with exposure to biopersistent fibers, mainly asbestos (80% of cases) and-in specific geographic regions-erionite, zeolites, ophiolites, and fluoro-edenite. Individuals with a chronic exposure to asbestos generally have a long latency with no or few symptoms. Then, when patients do become symptomatic, they present with advanced disease and a worse overall survival (about 13/15 months). The fibers from industrial production not only pose a substantial risk to workers, but also to their relatives and to the surrounding community. Modern targeted therapies that have shown benefit in other human tumors have thus far failed in MPM. Overall, MPM has been listed as orphan disease by the European Union. However, molecular high-throughput profiling is currently unveiling novel biomarkers and actionable targets. We here discuss the natural evolution, mainly focusing on the novel concept of molecular epidemiology. The application of innovative endpoints, quantification of genetic damages, and definition of genetic susceptibility are reviewed, with the ultimate goal to point out new tools for screening of exposed subject and for designing more efficient diagnostic and therapeutic strategies.}, } @article {pmid33799965, year = {2021}, author = {Schiavello, M and Gazzano, E and Bergandi, L and Silvagno, F and Libener, R and Riganti, C and Aldieri, E}, title = {Identification of Redox-Sensitive Transcription Factors as Markers of Malignant Pleural Mesothelioma.}, journal = {Cancers}, volume = {13}, number = {5}, pages = {}, pmid = {33799965}, issn = {2072-6694}, abstract = {Although asbestos has been banned in most countries around the world, malignant pleural mesothelioma (MPM) is a current problem. MPM is an aggressive tumor with a poor prognosis, so it is crucial to identify new markers in the preventive field. Asbestos exposure induces oxidative stress and its carcinogenesis has been linked to a strong oxidative damage, event counteracted by antioxidant systems at the pulmonary level. The present study has been focused on some redox-sensitive transcription factors that regulate cellular antioxidant defense and are overexpressed in many tumors, such as Nrf2 (Nuclear factor erythroid 2-related factor 2), Ref-1 (Redox effector factor 1), and FOXM1 (Forkhead box protein M1). The research was performed in human mesothelial and MPM cells. Our results have clearly demonstrated an overexpression of Nrf2, Ref-1, and FOXM1 in mesothelioma towards mesothelium, and a consequent activation of downstream genes controlled by these factors, which in turn regulates antioxidant defense. This event is mediated by oxidative free radicals produced when mesothelial cells are exposed to asbestos fibers. We observed an increased expression of Nrf2, Ref-1, and FOXM1 towards untreated cells, confirming asbestos as the mediator of oxidative stress evoked at the mesothelium level. These factors can therefore be considered predictive biomarkers of MPM and potential pharmacological targets in the treatment of this aggressive cancer.}, } @article {pmid33792699, year = {2021}, author = {Fujihira, H and Takakura, D and Matsuda, A and Abe, M and Miyazaki, M and Nakagawa, T and Kajino, K and Denda-Nagai, K and Noji, M and Hino, O and Irimura, T}, title = {Bisecting-GlcNAc on Asn388 is characteristic to ERC/mesothelin expressed on epithelioid mesothelioma cells.}, journal = {Journal of biochemistry}, volume = {170}, number = {3}, pages = {317-326}, pmid = {33792699}, issn = {1756-2651}, support = {JP19ae0101026//Japan Agency for Medical Research and Development/ ; 18K14655//Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research/ ; //Promotion and Mutual Aid Corporation for Private Schools of Japan/ ; }, mesh = {Acetylglucosamine/*metabolism ; Biomarkers, Tumor/metabolism ; Cell Line, Tumor ; Chromatography, Liquid/methods ; Epithelioid Cells/metabolism ; GPI-Linked Proteins/*metabolism ; Glycosylation ; Humans ; Lectins/*metabolism ; Mass Spectrometry/methods ; Mesothelin ; Mesothelioma/*metabolism ; Mesothelioma, Malignant/metabolism ; Protein Array Analysis/methods ; }, abstract = {Mesothelioma is a highly aggressive tumour associated with asbestos exposure and is histologically classified into three types: epithelioid-type, sarcomatoid-type and biphasic-type. The prognosis of mesothelioma patients is poor and there is no effective molecular-targeting therapy as yet. ERC/mesothelin is a glycoprotein that is highly expressed on several types of cancers including epithelioid mesothelioma, but also expressed on normal mesothelial cells. This is a predicted reason why there is no clinically approved therapeutic antibody targeting ERC/mesothelin. In the present study, we focussed on the differential glycosylation between ERC/mesothelin present on epithelioid mesothelioma and that on normal mesothelial cells and aimed to reveal a distinct feature of epithelioid mesothelioma cells. Lectin microarray analysis of ERC/mesothelin using cells and patient specimens showed significantly stronger binding of PHA-E4 lectin, which recognizes complex-type N-glycans having a so-called bisecting-GlcNAc structure, to ERC/mesothelin from epithelioid mesothelioma cells than that from normal mesothelial cells. Further, liquid chromatography/mass spectrometry analysis on ERC/mesothelin from epithelioid mesothelioma cells confirmed the presence of a bisecting-GlcNAc attached to Asn388 of ERC/mesothelin. These results suggest that this glycoproteome could serve as a potential target for the generation of a highly selective and safe therapeutic antibody for epithelioid mesothelioma.}, } @article {pmid33781046, year = {2021}, author = {Huang, XY and Ye, Q}, title = {[Asbestos exposure and asbestos-related malignant diseases:an epidemiological review].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {39}, number = {3}, pages = {233-236}, doi = {10.3760/cma.j.cn121094-20200226-00089}, pmid = {33781046}, issn = {1001-9391}, support = {2019-XZ-70//Consutting Research Project of Chinese Academy of Engineering/ ; Z181100001718118//Capital Clinical Character1stic Application Research/ ; }, mesh = {*Asbestos/adverse effects ; Carcinogens/toxicity ; Humans ; *Lung Neoplasms/chemically induced/epidemiology ; *Mesothelioma/chemically induced/epidemiology ; *Mesothelioma, Malignant ; *Occupational Exposure ; }, abstract = {Asbestos has high fire resistance, electrical insulation and thermal insulation. It is an important fire prevention, insulation and insulation material. It is widely used in industrial production and daily life. In 1987, the international agency for research on cancer (IARC) has listed asbestos as a class I carcinogen; in 2012, IARC confirmed that all types of asbestos have carcinogenic effect. By 2019, asbestos has been banned in 66 countries and regions around the world. Asbestos exposure increases the risk of human malignant tumor. Lung cancer and mesothelioma are known asbestos induced tumors. Epidemiological studies also support that asbestos exposure is related to the incidence of malignant tumors in reproductive system, digestive system, urinary system, nasopharynx head and neck. We summarized the epidemiological studies of asbestos induced tumors in order to provide reference for further research.}, } @article {pmid33778549, year = {2020}, author = {Gill, RR and Murphy, DJ and Seethamraju, RT and Mazzola, E and Bueno, R and Richards, WG}, title = {Interobserver Variability of Quantitative and Qualitative Assessment Using MRI in Malignant Pleural Mesothelioma.}, journal = {Radiology. Cardiothoracic imaging}, volume = {2}, number = {2}, pages = {e190066}, pmid = {33778549}, issn = {2638-6135}, support = {R01 CA120528/CA/NCI NIH HHS/United States ; }, abstract = {PURPOSE: To evaluate the interobserver variability associated with quantitative and qualitative MRI assessments of malignant pleural mesothelioma (MPM).

MATERIALS AND METHODS: Patients with MPM who underwent uniform-protocol preoperative MRI between 2009 and 2014 were included. The MRI-derived tumor volume was estimated. Unidimensional measurements of maximal pleural thickness (P max) and average pleural thickness (P avg) on axial MR images; maximal fissural thickness (F max); maximal diaphragmatic thickness (D max); and average diaphragmatic thickness (D avg) on sagittal reconstructed images were acquired. Interobserver agreement regarding the American Joint Committee on Cancer (AJCC) tumor stage at each criterion level was assessed by using Cohen κ statistics. Agreement between quantitative measurements was assessed by using Bland-Altman plots and intraclass correlation coefficients (ICCs).

RESULTS: The study cohort included 349 patients (median age, 68 years [age range, 30-90 years), 273 (78%) of whom were men and 203 (58%) of whom had epithelioid-subtype tumors. Qualitative assessment performed by using the AJCC staging criteria (eighth edition) was concordant in 31% of cases and yielded considerable disagreement (κ = 0.177). Inspection of the Bland-Altman plots led to decisive agreement between the two reviewers regarding MRI-derived tumor volume (ICC, 0.979). There was also a good degree of agreement between the two reviewers regarding unidimensional measurements of D max (ICC, 0.807), D avg (ICC, 0.823), P max (ICC, 0.787), P avg (ICC, 0.787), and F max (ICC, 0.659).

CONCLUSION: Quantitative assessment can enhance the clinical staging of MPM. Compared with qualitative assessment, quantitative assessment has low interobserver variability and could yield a tumor size criterion that is currently lacking in the AJCC clinical staging of MPM.Supplemental material is available for this article.© RSNA, 2020.}, } @article {pmid33775406, year = {2021}, author = {Klebe, S and Nakatani, Y and Dobra, K and Butnor, KJ and Roden, AC and Nicholson, AG and Marchevsky, AM and Husain, AN and Segal, A and Walts, AE and Weynand, B and Michael, CW and Dacic, S and Godbolt, D and Attanoos, R and Santoni-Rugiu, E and Galateau-Salle, F and Hiroshima, K and Moreira, AL and Burn, J and Nabeshima, K and Gibbs, AR and Churg, A and Litzky, LA and Brcic, L and Tsao, MS and Mino-Kenudson, M and Rørvig, SB and Tazelaar, HD and Krausz, T and Zhang, YZ and Chirieac, LR and Beasley, MB and Hjerpe, A}, title = {The concept of mesothelioma in situ, with consideration of its potential impact on cytology diagnosis.}, journal = {Pathology}, volume = {53}, number = {4}, pages = {446-453}, doi = {10.1016/j.pathol.2020.12.005}, pmid = {33775406}, issn = {1465-3931}, mesh = {Cytodiagnosis ; Early Diagnosis ; Humans ; Mesothelioma, Malignant/classification/*diagnosis/pathology/therapy ; Pathologists ; Serous Membrane/pathology ; Surveys and Questionnaires ; World Health Organization ; }, abstract = {Diffuse malignant mesothelioma (MM) is an incurable tumour of the serosal membranes, which is often caused by exposure to asbestos and commonly diagnosed at advanced stage. Malignant mesothelioma in situ (MMIS) is now included as diagnostic category by the World Health Organization (WHO). However, our international survey of 34 pulmonary pathologists with an interest in MM diagnosis highlights inconsistency regarding how the diagnosis is being made by experts, despite published guidelines. Whilst the WHO restricts the diagnosis to surgical samples, the very concept has implication for cytological diagnosis, which is already regarded as controversial in itself by some. MMIS is currently only applicable as precursor to MM with an epithelioid component, and raises the possibility for different molecular pathways for different histological MM subtypes. The clinical implications of MMIS at this stage are uncertain, but aggressive therapies are being initiated in some instances. Based on the results of the survey we here present a critical appraisal of the concept, its clinical and conceptual implications and provide practice suggestions for diagnosis. A low threshold for ancillary testing is suggested. The designations of 'malignant mesothelioma, cannot exclude MMIS' or 'atypical mesothelial proliferation with molecular indicators of malignancy, so-called MMIS' could be used on cytology samples, adding 'no evidence of invasion in sample provided' for surgical samples. Clinical and radiological correlation are integral to diagnosis and best done at multidisciplinary meetings. Finally, collaborative studies are required to improve our understanding of MMIS.}, } @article {pmid37034512, year = {2023}, author = {Simsek, FS and Cakmak, M and Kuslu, D and Balci, TA and In, E and Ozercan, IH and Narin, Y}, title = {How can we use positron emission tomography/computed tomography more accurately for characterization of asbestos-related pleural thickening?.}, journal = {Archives of medical science : AMS}, volume = {19}, number = {2}, pages = {385-391}, pmid = {37034512}, issn = {1734-1922}, abstract = {INTRODUCTION: There is no consensus about the standardized uptake value maximum (SUVmax) cut-off value to characterize pleural thickening worldwide. Sometimes, this causes unnecessary invasive diagnostic procedures. Our first aim is to determine a cut-off value for SUVmax. Secondly, we try to answer the following question: If we use this cut-off value together with morphological parameters, can we differentiate benign thickening from malignant pleural mesothelioma (MPM) more accurately?

MATERIAL AND METHODS: Thirty-seven patients who underwent 2-deoxy-2-fluoro-D-glucose ([[18]F]FDG) positron emission tomography/computed tomography (PET/CT) before pleural biopsy were included the study. All of patients had histopathologically proven primary pleural disease. Their [18F]FDG-PET/CT imaging reports were re-assessed. If a patient's SUVmax or size of the thickening was not mentioned in the report, we calculated it with their [18F]FDG-PET/CT.

RESULTS: Age, pleural effusion, size, and SUVmax were found to have a relationship with MPM. We found the size > 14 mm, and SUVmax > 4.0 as cut-off values for MPM. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for size > 14 mm were found to be 86.4%, 85.2%, 82.6%, 88.5%, respectively. For SUVmax > 4.0, sensitivity, specificity, PPV, NPV were 90.9%, 87.0%, 85.1%, 92.2%, respectively.

CONCLUSIONS: If a patient has SUVmax > 4.0 and/or size > 14 mm, the risk of MPM is high. These patients should undergo biopsy. If a patient's SUVmax < 4.0, size < 14 mm and does not have pleural effusion, he/she has low risk for MPM. These patients can undergo the follow-up. If a patient's SUVmax < 4, size < 14, and has pleural effusion the MPM risk is approximately 4%. These patients can undergo biopsy/cytology/follow-up. Novel studies are needed for these patients.}, } @article {pmid33749247, year = {2021}, author = {Reid, G and Klebe, S and van Zandwijk, N and George, AM}, title = {Asbestos and Zeolites: from A to Z via a Common Ion.}, journal = {Chemical research in toxicology}, volume = {34}, number = {4}, pages = {936-951}, doi = {10.1021/acs.chemrestox.0c00286}, pmid = {33749247}, issn = {1520-5010}, mesh = {Asbestos/*adverse effects/metabolism ; Humans ; Nanotubes, Carbon/adverse effects ; Zeolites/*adverse effects/metabolism ; }, abstract = {Asbestos and zeolites are silicate-based minerals, linked inextricably via paradoxical similarities and differences which have emanated from different geological epochs. Both have been employed in the service of humanity through millennia: asbestos, for its "inextinguishable" quality of being an insulator against heat and fire; zeolite, a "boiling stone" with its volcanic and marine sedimentary rock origins, for its propensity to adsorb water and remove metals and toxins. Serious adverse health effects observed in asbestos miners as long ago as the 1st Century AD did not halt the rising popularity of asbestos. As the miracle material of the 1900s, asbestos production and consumption exploded, culminating in its ubiquity in ships, vehicles, homes, commercial buildings, and over 3000 different industrial and household products. Through the 1940s and 1950s, epidemiological studies concluded that asbestos was a likely cause of asbestosis, lung cancer, and malignant mesothelioma, and it is now banned in many but far from all countries. The long latency between exposure to asbestos and the occurrence of cancer has obscured the deadly consequences of asbestos exposure for centuries. Even today, a considerable part of the world population is insufficiently aware of the dangers of asbestos, and millions of tons of this carcinogen continue to be mined and used worldwide. Zeolites, both natural and synthetic, are microporous aluminosilicate minerals commonly used in a myriad of processes, in the petrochemical industry, in domestic appliances and cleaning agents, as commercial adsorbents and exchangers for toxins and pollutants, and as catalysts. Zeolites are found in agriculture, veterinary science, and human health. More recently, new materials such as carbon nanotubes are being employed in materials requiring durability and thermal and electrical conductivity, yet nanotubes are now joining the ranks of more established particulates such as asbestos and silica, in causing human disease. In this review, we compare and contrast the similarities and differences of these two groups of silicate minerals and their waxing and waning use in the employ of humanity.}, } @article {pmid33741915, year = {2021}, author = {Zhang, M and Luo, JL and Sun, Q and Harber, J and Dawson, AG and Nakas, A and Busacca, S and Sharkey, AJ and Waller, D and Sheaff, MT and Richards, C and Wells-Jordan, P and Gaba, A and Poile, C and Baitei, EY and Bzura, A and Dzialo, J and Jama, M and Le Quesne, J and Bajaj, A and Martinson, L and Shaw, JA and Pritchard, C and Kamata, T and Kuse, N and Brannan, L and De Philip Zhang, P and Yang, H and Griffiths, G and Wilson, G and Swanton, C and Dudbridge, F and Hollox, EJ and Fennell, DA}, title = {Clonal architecture in mesothelioma is prognostic and shapes the tumour microenvironment.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {1751}, pmid = {33741915}, issn = {2041-1723}, support = {C61811/A24218/CRUK_/Cancer Research UK/United Kingdom ; /DH_/Department of Health/United Kingdom ; 25352/CRUK_/Cancer Research UK/United Kingdom ; 25253/CRUK_/Cancer Research UK/United Kingdom ; 20466/CRUK_/Cancer Research UK/United Kingdom ; 17786/CRUK_/Cancer Research UK/United Kingdom ; 30025/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {*Chromosome Deletion ; Clone Cells/metabolism/pathology ; Cluster Analysis ; Cohort Studies ; Humans ; Kaplan-Meier Estimate ; Lung Neoplasms/*genetics ; Mesothelioma/*genetics ; *Mutation ; Pleural Neoplasms/*genetics ; Prognosis ; Tumor Microenvironment/genetics ; Tumor Suppressor Proteins/classification/*genetics ; Exome Sequencing/methods ; }, abstract = {Malignant Pleural Mesothelioma (MPM) is typically diagnosed 20-50 years after exposure to asbestos and evolves along an unknown evolutionary trajectory. To elucidate this path, we conducted multi-regional exome sequencing of 90 tumour samples from 22 MPMs acquired at surgery. Here we show that exomic intratumour heterogeneity varies widely across the cohort. Phylogenetic tree topology ranges from linear to highly branched, reflecting a steep gradient of genomic instability. Using transfer learning, we detect repeated evolution, resolving 5 clusters that are prognostic, with temporally ordered clonal drivers. BAP1/-3p21 and FBXW7/-chr4 events are always early clonal. In contrast, NF2/-22q events, leading to Hippo pathway inactivation are predominantly late clonal, positively selected, and when subclonal, exhibit parallel evolution indicating an evolutionary constraint. Very late somatic alteration of NF2/22q occurred in one patient 12 years after surgery. Clonal architecture and evolutionary clusters dictate MPM inflammation and immune evasion. These results reveal potentially drugable evolutionary bottlenecking in MPM, and an impact of clonal architecture on shaping the immune landscape, with potential to dictate the clinical response to immune checkpoint inhibition.}, } @article {pmid33718042, year = {2021}, author = {Schiopu, SRI and Käsmann, L and Schönermarck, U and Fischereder, M and Grabmaier, U and Manapov, F and Rauch, J and Orban, M}, title = {Pembrolizumab-induced myocarditis in a patient with malignant mesothelioma: plasma exchange as a successful emerging therapy-case report.}, journal = {Translational lung cancer research}, volume = {10}, number = {2}, pages = {1039-1046}, pmid = {33718042}, issn = {2218-6751}, abstract = {Malignant mesothelioma is an aggressive cancer associated with prior exposure to asbestos and dismal prognosis. Immune checkpoint inhibitor therapy is currently approved by the Food and Drug Administration for pre-treated malignant pleural mesothelioma. We describe a 75-year-old patient with disseminated, progressive malignant mesothelioma receiving 2 cycles of pembrolizumab who presented with generalized muscle weakness, shortness of breath, double vision and ptosis. There was no previous history of cardiovascular disease. The clinical picture, supported by the detection of anti-titin autoantibodies suggested myasthenia gravis (MG). Also, cardiac biomarkers were elevated. Echocardiography showed new severely reduced ejection fraction. A 12-lead resting electrocardiogram (ECG) revealed ST segment elevation in the posterior leads with polymorphic ventricular extrasystoles. Because cardiac catheterization revealed no relevant coronary lesions, immune checkpoint inhibitor-associated myocarditis and MG were suspected. Management and Outcome: The patient was started on steroids. Within a few days of presentation respiratory failure set in and the patient was intubated. Recurrent arrhythmias followed, which were treated by repeated emergency electrical cardioversion. In order to relieve myasthenic symptoms, plasma exchange was initiated and 10 cycles were carried out. This consequently also led to an improvement of myocarditis. Upon discharge, the ejection fraction recovered. The patient recovered and was alive at 1-year follow-up, without relevant limitations to his quality of life. Discussion and Conclusion: The article further discusses the use of plasma exchange for immune checkpoint inhibitor-associated myocarditis based on a review of literature. We conclude that patients showing no improvement after steroid therapy for immune checkpoint inhibitor-related myocarditis should be evaluated for plasma exchange, which appears to be an effective treatment option.}, } @article {pmid33713739, year = {2021}, author = {Sun, S and Frontini, F and Qi, W and Hariharan, A and Ronner, M and Wipplinger, M and Blanquart, C and Rehrauer, H and Fonteneau, JF and Felley-Bosco, E}, title = {Endogenous retrovirus expression activates type-I interferon signaling in an experimental mouse model of mesothelioma development.}, journal = {Cancer letters}, volume = {507}, number = {}, pages = {26-38}, doi = {10.1016/j.canlet.2021.03.004}, pmid = {33713739}, issn = {1872-7980}, mesh = {Animals ; Asbestos, Crocidolite ; Asbestosis/complications ; Cell Line, Tumor ; DNA Methylation ; Disease Models, Animal ; Endogenous Retroviruses/genetics/metabolism/*pathogenicity ; Gene Expression Regulation, Neoplastic ; Host-Pathogen Interactions ; Interferon Regulatory Factors/genetics/metabolism ; Interferon Type I/genetics/*metabolism ; Mesothelioma/etiology/genetics/metabolism/*virology ; Mice ; Promoter Regions, Genetic ; *RNA Editing ; RNA, Double-Stranded/genetics/*metabolism ; Signal Transduction ; }, abstract = {Early events in an experimental model of mesothelioma development include increased levels of editing in double-stranded RNA (dsRNA). We hypothesised that expression of endogenous retroviruses (ERV) contributes to dsRNA formation and type-I interferon signaling. ERV and interferon stimulated genes (ISGs) expression were significantly higher in tumor compared to non-tumor samples. 12 tumor specific ERV ("MesoERV1-12") were identified and verified by qPCR in mouse tissues. "MesoERV1-12" expression was lower in mouse embryonic fibroblasts (MEF) compared to mesothelioma cells. "MesoERV1-12" levels were significantly increased by demethylating agent 5-Aza-2'-deoxycytidine treatment and were accompanied by increased levels of dsRNA and ISGs. Basal ISGs expression was higher in mesothelioma cells compared to MEF and was significantly decreased by JAK inhibitor Ruxolitinib, by blocking Ifnar1 and by silencing Mavs. "MesoERV7" promoter was demethylated in asbestos-exposed compared to sham mice tissue as well as in mesothelioma cells and MEF upon 5-Aza-CdR treatment. These observations uncover novel aspects of asbestos-induced mesothelioma whereby ERV expression increases due to promoter demethylation and is paralleled by increased levels of dsRNA and activation of type-I IFN signaling. These features are important for early diagnosis and therapy.}, } @article {pmid33692175, year = {2021}, author = {Shamseddin, M and Obacz, J and Garnett, MJ and Rintoul, RC and Francies, HE and Marciniak, SJ}, title = {Use of preclinical models for malignant pleural mesothelioma.}, journal = {Thorax}, volume = {76}, number = {11}, pages = {1154-1162}, pmid = {33692175}, issn = {1468-3296}, support = {BRC-1215-20014/DH_/Department of Health/United Kingdom ; G1002610/MRC_/Medical Research Council/United Kingdom ; MR/V028669/1/MRC_/Medical Research Council/United Kingdom ; MR/R009120/1/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; /CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Animals ; *Asbestos ; *Lung Neoplasms ; *Mesothelioma ; *Mesothelioma, Malignant ; Mice ; *Pleural Neoplasms ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive cancer most commonly caused by prior exposure to asbestos. Median survival is 12-18 months, since surgery is ineffective and chemotherapy offers minimal benefit. Preclinical models that faithfully recapitulate the genomic and histopathological features of cancer are critical for the development of new treatments. The most commonly used models of MPM are two-dimensional cell lines established from primary tumours or pleural fluid. While these have provided some important insights into MPM biology, these cell models have significant limitations. In order to address some of these limitations, spheroids and microfluidic chips have more recently been used to investigate the role of the three-dimensional environment in MPM. Efforts have also been made to develop animal models of MPM, including asbestos-induced murine tumour models, MPM-prone genetically modified mice and patient-derived xenografts. Here, we discuss the available in vitro and in vivo models of MPM and highlight their strengths and limitations. We discuss how newer technologies, such as the tumour-derived organoids, might allow us to address the limitations of existing models and aid in the identification of effective treatments for this challenging-to-treat disease.}, } @article {pmid33691361, year = {2021}, author = {Yu, M and Yu, M and Zhu, LJ and Yuan, XY and Zhang, X}, title = {[Expression and clinical significance of SETD2 in maligant pleural mesothelioma].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {39}, number = {2}, pages = {91-98}, doi = {10.3760/cma.j.cn121094-20200831-00505}, pmid = {33691361}, issn = {1001-9391}, support = {11-ZC02//The Key Program of Zhejiang Medical Science: Occupational Health Sciences/ ; 2019D002//The Funding of Zhejiang Academy of Medical Sciences/ ; }, mesh = {*Asbestos ; Histone-Lysine N-Methyltransferase ; Humans ; *Lung Neoplasms/genetics ; *Mesothelioma/genetics ; *Mesothelioma, Malignant ; *Pleural Neoplasms/genetics ; Protein Serine-Threonine Kinases ; Tumor Suppressor Proteins ; Ubiquitin Thiolesterase ; }, abstract = {Objective: To analyze the gene mutation profile in malignant pleural mesothelioma (MPM) and investigate the expression of high-frequency mutant genes and its relationship with clinicopathological parameters. To screen out key genes and clinicopathologic factors related to the prognosis of MPM patients. Methods: The second generation sequencing data, somatic mutation data and clinical pathological data of 86 MPM cases and gene chip expression data of 89 MPM cases were downloaded from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) in March 2020. Summarize the gene mutation profile of tissue samples in the TCGA database and analyze the relationship between the expression level of high-frequency mutation genes and the clinicopathological characteristics, asbestos exposure history and prognosis of MPM patients. The genes significantly related to MPM prognosis were screened out for gene set enrichment analysis (GSEA) . Survival analysis and GSEA were performed for the selected key genes and clinicopathological features verification using the microarray expression data from the GEO database. Results: The top 10 genes with highest single nucleotide variations frequencies were BAP1, NF2, TP53, TTN, SETD2, LATS2, CCDC168, FAT4, PTCH1 and ZNF469. The high expression rates of NF2, TP53, SETD2 and CCDC168 genes in wild type were higher than those of mutated type, and the differences were statistically significant (P<0.05) . Cox multivariate analysis of TCGA data showed that MPM patients with epithelial type (HR=0.425, 95%CI: 0.235-0.767, P<0.01) and SETD2 low expression (HR=0.516, 95%CI: 0.307-0.868, P=0.011) had lower risk of death. The survival analysis of GEO data verified that patients with epithelial type MPM had longer survival time, while patients with sarcoma type MPM had shortest survival time (P<0.01) . GSEA showed that SETD2 was involved in G2M checkpoint, E2F targets, MYC signaling pathways, protein secretion, mitotic spindle, MTORC1 pathway, TGF-β pathway, androgen response and uv response. Conclusion: MPM is accompanied with higher frequency of gene mutations represented by BAP1, NF2, TP53, TTN, SETD2, LATS2 and so on. SETD2 expression level and epithelia type of MPM may be influential factors for MPM prognosis.}, } @article {pmid33691360, year = {2021}, author = {Yu, M and Yu, M and Ying, SB and Yuan, XY and Jiang, ZQ and Lou, JL and Zhu, LJ and Zhang, X}, title = {[The impact of CD8 and CTLA-4 expression on histopathological character and survival in mesothelioma].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {39}, number = {2}, pages = {85-90}, doi = {10.3760/cma.j.cn121094-20200831-00506}, pmid = {33691360}, issn = {1001-9391}, support = {2017183851//The Project of Zhejiang Medical & Health Science/ ; 2019D002//The Funding of Zhejiang Academy of Medical Sciences/ ; 11-ZC02//The Key Program of Zhejiang Medical Science: Occupational Health Sciences/ ; }, mesh = {CD8-Positive T-Lymphocytes ; CTLA-4 Antigen ; Humans ; Ki-67 Antigen ; *Mesothelioma ; *Mesothelioma, Malignant ; Retrospective Studies ; }, abstract = {Objective: To investigate the survival and death risk factors of mesothelioma cases stratified by the expression levels of CD8 and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) , providing new clue to evaluate disease progression and clinical outcome. Methods: This was a retrospective case report, which included 47 clinically and pathologically confirmed mesothelioma cases on November 2016. Their clinical and pathological information, asbestos exposure history and survival data were collected. Infiltrated lymphocyte, 5-methylcytosine (5-mC) , CTLA-4, CD8 and Ki-67 antigen were detected using hematoxylin-eosin staining and immunohistochemistry. Survival time and death risk factors of mesothelioma patients with different CD8 and CTLA-4 protein expression characteristics were analyzed. And analyze the influence of Ki-67 expression on the survival of patients with different CD8 and CTLA-4 protein and gene expression characteristics. Results: Among the 47 cases, 63.8% (30/47) had low/medium level of infiltrated lymphocyte. The immunohistochemistry scores of CTLA-4, CD8, 5-mC and Ki-67 were 92.97 (54.95, 120.65) , 72.41 (36.62, 89.82) , 11.09 (3.40, 52.89) and 5.88 (2.41, 11.48) , respectively. Patients with CD8(high) CTLA-4(high) had higher 5-mC level than those with CD8(high) CTLA-4(low) (P<0.01) . The median survival time of 27 cases was 0.83±0.29 year. The median survival times of those with CD8(high) CTLA-4(high) and CD8(high) CTLA-4(low) were 0.58±0.51 year and 0.83±0.30 year, respectively (P=0.521) . The immunohistochemistry score of Ki-67 ≥5.88 was an independent death risk factor for patients with CD8(high) CTLA-4(low) (HR=8.40, P=0.01) . Under different CD8 and CTLA-4 protein expression characteristics, in the patients with CD8(high) CTLA-4(low), the median survival times of those with high and low Ki-67 expression were 0.57±0.11 years and 2.31±0.46 years, respectively (P<0.01) . Under different CD8 and CTLA-4 mRNA expression characteristics, in the patients with CD8(high) CTLA-4(low), the median survival times of those with high and low Ki-67 mRNA expression were 1.20±0.36 years and 3.38±0.43 years, respectively (P=0.018) . Conclusion: Mesothelioma case with high CD8 but low CTLA-4 content might coexist DNA hypomethylation. In the presence of high Ki-67 expression, their survival time appears to be shortened with increased death risk.}, } @article {pmid33691359, year = {2021}, author = {Zhang, X}, title = {[Indispensable urgency for prevention and control of asbestos-related cancer].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {39}, number = {2}, pages = {81-84}, doi = {10.3760/cma.j.cn121094-20200831-00504}, pmid = {33691359}, issn = {1001-9391}, mesh = {*Asbestos ; *Asbestosis ; Humans ; *Lung Neoplasms ; *Mesothelioma ; *Neoplasms ; *Occupational Exposure ; }, } @article {pmid33691040, year = {2021}, author = {García López, V}, title = {[Programs for Asbestos Abatement. Lessons from Poland].}, journal = {Archivos de prevencion de riesgos laborales}, volume = {24}, number = {1}, pages = {62-73}, doi = {10.12961/aprl.2021.24.01.06}, pmid = {33691040}, issn = {1578-2549}, mesh = {*Asbestos/adverse effects/analysis ; Europe ; Humans ; *Mesothelioma/epidemiology/etiology/prevention & control ; *Occupational Exposure/prevention & control ; Poland ; Spain ; }, abstract = {The commercialization of asbestos in Europe in the second half of the 20th century translated into consumption of millions of tons of this material. Occupational exposure to asbestos is controlled under the 2009 European Union Directive. Currently, through epidemiological surveillance and pathology registries (mainly mesotheliomas), it is possible to record past exposures. Despite prohibiting its use, large amounts of asbestos remain in buildings, infrastructures and vehicles, among others. The road to elimination of existing asbestos began with a 2013 European Parliament Resolution and the Opinion of the European Economic and Social Committee (2015 / C 251/03).To better understand barriers to implementing these plans, we reviewed the experience in Poland the only country that to date has implemented an action plan with great financial support, together with actions carried out in Spain generally, and Navarre specifically, given the latter's exhaustive registry of exposed workers.The enormous economic effort required to implement these plans, along with the environmental risks associated with asbestos abatement, require detailed planning, which should consider understanding why the objectives set by Poland, a benchmark country, have not been achieved to date.}, } @article {pmid33678145, year = {2021}, author = {Carey, RN and Pfau, JC and Fritzler, MJ and Creaney, J and de Klerk, N and W Bill Musk, A and Franklin, P and Sodhi-Berry, N and Brims, F and Reid, A}, title = {Autoantibodies and cancer among asbestos-exposed cohorts in Western Australia.}, journal = {Journal of toxicology and environmental health. Part A}, volume = {84}, number = {11}, pages = {475-483}, pmid = {33678145}, issn = {1528-7394}, support = {UL1 TR002319/TR/NCATS NIH HHS/United States ; }, mesh = {Aged ; Asbestos/*adverse effects ; Autoantibodies/*blood ; Female ; Humans ; Lung Neoplasms/chemically induced/*immunology ; Male ; Mesothelioma, Malignant/chemically induced/*immunology ; Middle Aged ; Mining ; Occupational Exposure/*adverse effects ; Western Australia ; }, abstract = {Asbestos exposure is associated with many adverse health conditions including malignant mesothelioma and lung cancer as well as production of autoantibodies. Autoantibodies may serve as biomarkers for asbestos exposure in patients with cancer, and autoimmune dysfunction has been linked to increased rates of various cancers. The aim of this study was to examine the hypothesis that autoantibodies are more frequent in asbestos-exposed individuals with either lung cancer or mesothelioma than those without these conditions. Asbestos-exposed individuals from Western Australia who had lung cancer (n = 24), malignant mesothelioma (n = 24), or no malignancy (n = 51) were tested for antinuclear autoantibodies (ANA) using indirect immunofluorescence and specific extractable nuclear autoantibodies (ENA) employing a multiplexed addressable laser bead immunoassay. Contrary to the hypothesis, data demonstrated that individuals without malignancy were more likely to be positive for ANA compared to those with cancer. However, autoantibodies to histone and Ro-60 were found to be associated with lung cancer. These results support a possible predictive value for specific autoantibodies in the early detection of lung cancer and/or in our understanding of the role of autoimmune processes in cancer. However, further studies are needed to identify specific target antigens for the antibodies.}, } @article {pmid33673264, year = {2021}, author = {Arachi, D and Furuya, S and David, A and Mangwiro, A and Chimed-Ochir, O and Lee, K and Tighe, P and Takala, J and Driscoll, T and Takahashi, K}, title = {Development of the "National Asbestos Profile" to Eliminate Asbestos-Related Diseases in 195 Countries.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {4}, pages = {}, pmid = {33673264}, issn = {1660-4601}, mesh = {*Asbestos/toxicity ; Humans ; Income ; *Mesothelioma ; World Health Organization ; }, abstract = {Worldwide, 230,000+ people die annually from asbestos-related diseases (ARDs). The World Health Organization (WHO) recommends that countries develop a National Asbestos Profile (NAP) to eliminate ARDs. For 195 countries, we assessed the global status of NAPs (A: bona fide NAP, B: proxy NAP, C: relevant published information, D: no relevant information) by national income (HI: high, UMI: upper-middle, LMI: lower-middle, LI: low), asbestos bans (banned, no-ban) and public data availability. Fourteen (7% of 195) countries were category A (having a bona fide NAP), while 98, 51 and 32 countries were categories B, C and D, respectively. Of the 14 category-A countries, 8, 3 and 3 were LMI, UMI and HI, respectively. Development of a bona fide NAP showed no gradient by national income. The proportions of countries having a bona fide NAP were similar between asbestos-banned and no-ban countries. Public databases useful for developing NAPs contained data for most countries. Irrespective of the status of national income or asbestos ban, most countries have not developed a NAP despite having the potential. The global status of NAP is suboptimal. Country-level data on asbestos and ARDs in public databases can be better utilized to develop NAPs for globally eliminating ARDs.}, } @article {pmid33669843, year = {2021}, author = {Visonà, SD and Capella, S and Bodini, S and Borrelli, P and Villani, S and Crespi, E and Frontini, A and Colosio, C and Belluso, E}, title = {Inorganic Fiber Lung Burden in Subjects with Occupational and/or Anthropogenic Environmental Asbestos Exposure in Broni (Pavia, Northern Italy): An SEM-EDS Study on Autoptic Samples.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {4}, pages = {}, pmid = {33669843}, issn = {1660-4601}, mesh = {*Asbestos ; Environmental Exposure ; Humans ; Italy/epidemiology ; Lung ; *Lung Neoplasms/epidemiology/etiology ; *Mesothelioma/chemically induced/epidemiology ; *Occupational Exposure/adverse effects ; Tumor Microenvironment ; }, abstract = {Increased mortality due to malignant mesothelioma has been demonstrated by several epidemiologic studies in the area around Broni (a small town in Lombardy, northern Italy), where a factory producing asbestos cement was active between 1932 and 1993. Until now, the inorganic fiber burden in lungs has not been investigated in this population. The aim of this study is to assess the lung fiber burden in 72 individuals with previous occupational and/or anthropogenic environmental exposure to asbestos during the activity of an important asbestos cement factory. Inorganic fiber lung burden was assessed in autoptic samples taken from individuals deceased from asbestos-related diseases using a scanning electron microscope equipped with an energy-dispersive spectrometer. Significant differences in the detected amount of asbestos were pointed out among the three types of exposure. In most lung samples taken from patients who died of mesothelioma, very little asbestos (or, in some cases, no fibers) was found. Such subjects showed a significantly lower median amount of asbestos as compared to asbestosis. Almost no chrysotile was detected in the examined samples. Overall, crocidolite was the most represented asbestos, followed by amosite, tremolite/actinolite asbestos, and anthophyllite asbestos. There were significant differences in the amount of crocidolite and amosite fibers according to the kind of exposure. Overall, these findings provide novel insights into the link between asbestos exposure and mesothelioma, as well as the different impacts of the various types of asbestos on human health in relation to their different biopersistences in the lung microenvironment.}, } @article {pmid33669318, year = {2021}, author = {Gariazzo, C and Binazzi, A and Alfò, M and Massari, S and Stafoggia, M and Marinaccio, A}, title = {Predictors of Lung Cancer Risk: An Ecological Study Using Mortality and Environmental Data by Municipalities in Italy.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {4}, pages = {}, pmid = {33669318}, issn = {1660-4601}, mesh = {*Asbestos/toxicity ; Cities ; Environmental Exposure/adverse effects ; Female ; Humans ; Italy/epidemiology ; *Lung Neoplasms/epidemiology/etiology ; Male ; *Mesothelioma/epidemiology ; *Occupational Exposure ; }, abstract = {Lung cancer (LC) mortality remains a consistent part of the total deaths occurring worldwide. Its etiology is complex as it involves multifactorial components. This work aims in providing an epidemiological assessment on occupational and environmental factors associated to LC risk by means of an ecological study involving the 8092 Italian municipalities for the period 2006-2015. We consider mortality data from mesothelioma as proxy of asbestos exposure, as well as PM2.5 and radon levels as a proxy of environmental origin. The compensated cases for occupational respiratory diseases, urbanization and deprivation were included as predictors. We used a negative binomial distribution for the response, with analysis stratified by gender. We estimated that asbestos is responsible for about 1.1% (95% CI: 0.8, 1.4) and 0.5% (95% CI: 0.2, 0.8) of LC mortality in males and females, respectively. The corresponding figures are 14.0% (95% CI: 12.5, 15.7) and 16.3% (95% CI: 16.2, 16.3) for PM2.5 exposure, and 3.9% (95% CI: 3.5, 4.2) and 1.6% (95% CI: 1.4, 1.7) for radon exposure. The assessment of determinants contribution to observed LC deaths is crucial for improving awareness of its origin, leading to increase the equity of the welfare system.}, } @article {pmid33668103, year = {2021}, author = {Wortzel, JD and Wiebe, DJ and Elahi, S and Agawu, A and Barg, FK and Emmett, EA}, title = {Ascertainment Bias in a Historic Cohort Study of Residents in an Asbestos Manufacturing Community.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {5}, pages = {}, pmid = {33668103}, issn = {1660-4601}, support = {P30 ES013508/ES/NIEHS NIH HHS/United States ; P42 ES023720/NH/NIH HHS/United States ; P30 ES013508/NH/NIH HHS/United States ; }, mesh = {Adult ; Aged ; *Asbestos ; Cohort Studies ; Environmental Exposure ; Female ; Humans ; *Lung Neoplasms ; *Mesothelioma ; Middle Aged ; *Occupational Exposure ; Young Adult ; }, abstract = {This paper describes follow-up for a cohort of 4530 residents living in the asbestos manufacturing community of Ambler, PA, U.S. in 1930. Using re-identified census data, cause and date of death data obtained from the genealogic website Ancestry.com, along with geospatial analysis, we explored relationships among demographic characteristics, occupational, paraoccupational and environmental asbestos exposures. We identified death data for 2430/4530 individuals. Exposure differed significantly according to race, gender, age, and recency of immigration to the U.S. Notably, there was a significant difference in the availability of year of death information for non-white vs. white individuals (odds ratio (OR) = 0.62 p-value < 0.001), females (OR = 0.53, p-value < 0.001), first-generation immigrants (OR = 0.67, p-value = 0.001), second-generation immigrants (OR = 0.31, p-value < 0.001) vs. non-immigrants, individuals aged less than 20 (OR = 0.31 p-value < 0.001) and individuals aged 20 to 59 (OR = 0.63, p-value < 0.001) vs. older individuals. Similarly, the cause of death was less often available for non-white individuals (OR = 0.42, p-value <0.001), first-generation immigrants and (OR = 0.71, p-value = 0.009), second-generation immigrants (OR = 0.49, p-value < 0.001), individuals aged less than 20 (OR = 0.028 p-value < 0.001), and individuals aged 20 to 59 (OR = 0.26, p-value < 0.001). These results identified ascertainment bias that is important to consider in analyses that investigate occupational, para-occupational and environmental asbestos exposure as risk factors for mortality in this historic cohort. While this study attempts to describe methods for assessing itemized asbestos exposure profiles for a community in 1930 using Ancestry.com and other publicly accessible databases, it also highlights how historic cohort studies likely underestimate the impact of asbestos exposure on vulnerable populations. Future work will aim to assess mortality patterns in this cohort.}, } @article {pmid33662805, year = {2021}, author = {Kotsiou, OS and Gourgoulianis, KI and Zarogiannis, SG}, title = {The role of nitric oxide in pleural disease.}, journal = {Respiratory medicine}, volume = {179}, number = {}, pages = {106350}, doi = {10.1016/j.rmed.2021.106350}, pmid = {33662805}, issn = {1532-3064}, mesh = {Anti-Inflammatory Agents ; Asbestos/adverse effects ; Biomarkers/metabolism ; Humans ; Mesothelioma/diagnosis/etiology ; Nitric Oxide/metabolism/pharmacology/*physiology ; Nitric Oxide Donors/pharmacology ; Pleura/metabolism ; Pleural Diseases/diagnosis/*etiology/therapy ; Signal Transduction ; }, abstract = {Nitric oxide (NO) regulates various physiological and pathophysiological functions in the lungs. However, there is much less information about the effects of NO in the pleura. The present review aimed to explore the available evidence regarding the role of NO in pleural disease. NO, has a double-edged role in the pleural cavity. It is an essential signaling molecule mediating various physiological cell functions such as lymphatic drainage of the serous cavities, the immune response to intracellular multiplication of pathogens, and downregulation of neutrophil migration, but also induces genocytotoxic and mutagenic effects when present in excess. NO is implicated in the pathogenesis of asbestos-related or exudative pleural disease and mesothelioma. From a clinical point of view, the fraction of exhaled NO has been suggested as a potential non-invasive tool for the diagnosis of benign asbestos-related disorders. Under experimental conditions, NO-mimetics were found to attenuate hypoxia-induced therapy resistance in mesothelioma. Similarly, hybrid agents consisting of an NO donor coupled with a parent anti-inflammatory drug showed an enhancement of the anti-inflammatory activity of anti-inflammatory drugs. However, given the paucity of research work performed over the last years in this area, further research should be undertaken to establish reliable conclusions with respect to the feasibility of determining or targeting the NO signaling pathway for pleural disease diagnosis and therapeutic management.}, } @article {pmid33660947, year = {2021}, author = {Guzmán-Casta, J and Carrasco-CaraChards, S and Guzmán-Huesca, J and Sánchez-Ríos, CP and Riera-Sala, R and Martínez-Herrera, JF and Peña-Mirabal, ES and Bonilla-Molina, D and Alatorre-Alexander, JA and Martínez-Barrera, LM and Rodríguez-Cid, JR}, title = {Prognostic factors for progression-free and overall survival in malignant pleural mesothelioma.}, journal = {Thoracic cancer}, volume = {12}, number = {7}, pages = {1014-1022}, pmid = {33660947}, issn = {1759-7714}, mesh = {Adolescent ; Adult ; Female ; Humans ; Male ; Mesothelioma, Malignant/*mortality ; Prognosis ; Progression-Free Survival ; Retrospective Studies ; Young Adult ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma is an infrequent neoplasia with a poor prognosis and the majority of patients already have advanced disease at the time of presentation. Exposure to asbestos is the most important risk factor for malignant pleural mesothelioma. Mesothelioma is a neoplasia with a long preclinical stage that can span from 15 to 40 years.

METHODS: This was a descriptive, observational, retrospective study of 136 patients with a confirmed diagnosis of mesothelioma, which compared histological subtypes, immunohistochemical biomarkers, concomitant chronic degenerative diseases, tobacco use, age at the time of diagnosis, clinical stage and chemotherapy agents used or other treatments such as radiotherapy and surgery to identify all the factors that impact in the prognosis of overall survival (OS) and progression-free survival (PFS).

RESULTS: A total of 136 patients were included in the study. In the total study population, 84 patients were male (61.8%) and 52 were female (38.2%). Median PFS was nine months (95% confidence interval [CI]: 8.4-9.5 months) and median OS was 12 months (95% CI: 11.3-12.6). The results indicated that the most determining prognostic factors for OS and PFS were cell differentiation measured by immunohistochemical biomarkers, the treatment chosen, and that RECIST was the most significant in the evaluation of patient response to treatment.

CONCLUSIONS: Malignant pleural mesothelioma is a cancer with a poor prognosis usually diagnosed at an advanced stage of disease. Our study revealed that the prognostic factors for OS and PS were cell differentiation, the treatment chosen and RECIST.}, } @article {pmid33655329, year = {2021}, author = {Yamamoto, S and Lee, S and Ariyasu, T and Endo, S and Miyata, S and Yasuda, A and Harashima, A and Ohta, T and Kumagai-Τakei, N and Ito, T and Shimizu, Y and Srinivas, B and Sada, N and Nishimura, Y and Otsuki, T}, title = {Ingredients such as trehalose and hesperidin taken as supplements or foods reverse alterations in human T cells, reducing asbestos exposure-induced antitumor immunity.}, journal = {International journal of oncology}, volume = {58}, number = {4}, pages = {}, pmid = {33655329}, issn = {1791-2423}, mesh = {Asbestos/*adverse effects ; CD4-Positive T-Lymphocytes/drug effects/*immunology/metabolism ; Cells, Cultured ; *Dietary Supplements ; Hesperidin/*pharmacology ; Humans ; Interferon-gamma/immunology ; Interleukin-17/immunology ; Male ; Mesothelioma, Malignant/chemically induced/*immunology/prevention & control ; Middle Aged ; Receptors, CXCR3/immunology ; Trehalose/*pharmacology ; }, abstract = {Exposure of human immune cells to asbestos causes a reduction in antitumor immunity. The present study aimed to investigate the recovery of reduced antitumor immunity by several ingredients taken as supplements or foods, including trehalose (Treh) and glycosylated hesperidin (gHesp). Peripheral blood CD4[+] cells were stimulated with IL‑2, anti‑CD3 and anti‑CD28 antibodies for 3 days, followed by further stimulation with IL‑2 for 7 days. Subsequently, cells were stimulated with IL‑2 for an additional 28 days. During the 28 days, cells were cultured in the absence or presence of 50 µg/ml chrysotile asbestos fibers. In addition, cells were treated with 10 mM Treh or 10 µM gHesp. Following culture for 28 days, reverse transcription‑quantitative PCR was performed to assess the expression levels of transcription factors, cytokines and specific genes, including matrix metalloproteinase‑7 (MMP‑7), nicotinamide nucleotide transhydrogenase (NNT) and C‑X‑C motif chemokine receptor 3, in unstimulated cells (fresh) and cells stimulated with PMA and ionomycin (stimuli). The results demonstrated that compared with the control group, chrysotile‑exposure induced alterations in MMP‑7, NNT and IL‑17A expression levels were not observed in the 'Treh' and 'gHesp' groups in stimulated cells. The results suggested that Treh and gHesp may reverse asbestos exposure‑induced reduced antitumor immunity in T helper cells. However, further investigation is required to confirm the efficacy of future trials involving the use of these compounds with high‑risk human populations exposed to asbestos, such as workers involved in asbestos‑handling activities.}, } @article {pmid33652123, year = {2021}, author = {Sridharan, S and Taylor-Just, A and Bonner, JC}, title = {Osteopontin mRNA expression by rat mesothelial cells exposed to multi-walled carbon nanotubes as a potential biomarker of chronic neoplastic transformation in vitro.}, journal = {Toxicology in vitro : an international journal published in association with BIBRA}, volume = {73}, number = {}, pages = {105126}, pmid = {33652123}, issn = {1879-3177}, support = {P30 ES025128/ES/NIEHS NIH HHS/United States ; R01 ES020897/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Biomarkers ; Cell Line ; Cell Transformation, Neoplastic/*genetics ; Epithelial Cells/*drug effects/metabolism ; Male ; Mesothelioma/genetics ; Nanotubes, Carbon/*toxicity ; Osteopontin/*genetics ; Pleura/cytology ; RNA, Messenger ; Rats, Inbred F344 ; Rats ; }, abstract = {Mesothelioma is a cancer of the lung pleura primarily associated with inhalation of asbestos fibers. Multi-walled carbon nanotubes (MWCNTs) are engineered nanomaterials that pose a potential risk for mesothelioma due to properties that are similar to asbestos. Inhaled MWCNTs migrate to the pleura in rodents and some types cause mesothelioma. Like asbestos, there is a diversity of MWCNT types. We investigated the neoplastic potential of tangled (tMWCNT) versus rigid (rMWCNT) after chronic exposure using serial passages of rat mesothelial cells in vitro. Normal rat mesothelial (NRM2) cells were exposed to tMWCNTs or rMWCNTs for 45 weeks over 85 passages to determine if exposure resulted in transformation to a neoplastic phenotype. Rat mesothelioma (ME1) cells were used as a positive control. Osteopontin (OPN) mRNA was assayed as a biomarker of transformation by real time quantitative polymerase chain reaction (qPCR) and transformation was determined by a cell invasion assay. Exposure to rMWCNTs, but not tMWCNTs, resulted in transformation of NRM2 cells into an invasive phenotype that was similar to ME1 cells. Moreover, exposure of NRM2 cells to rMWCNTs increased OPN mRNA that correlated with cellular transformation. These data suggest that OPN is a potential biomarker that should be further investigated to screen the carcinogenicity of MWCNTs in vitro.}, } @article {pmid33640705, year = {2021}, author = {Niu, X and Zhou, C and Hu, A and Su, L and Lin, D and Han, H and Lu, Y}, title = {Malignant mesothelioma without asbestos exposure diagnosed during EGFR-TKI treatment of lung adenocarcinoma: A case report.}, journal = {Cancer treatment and research communications}, volume = {27}, number = {}, pages = {100345}, doi = {10.1016/j.ctarc.2021.100345}, pmid = {33640705}, issn = {2468-2942}, mesh = {Adenocarcinoma of Lung/diagnosis/*drug therapy/genetics ; Antineoplastic Combined Chemotherapy Protocols/pharmacology/therapeutic use ; Drug Resistance, Neoplasm ; ErbB Receptors/antagonists & inhibitors/genetics ; Fatal Outcome ; Humans ; Lung Neoplasms/diagnosis/*drug therapy/genetics ; Male ; Mesothelioma, Malignant/*diagnosis/drug therapy/genetics/secondary ; Middle Aged ; Neoplasms, Multiple Primary/*diagnosis/drug therapy/genetics/pathology ; Pleural Neoplasms/*diagnosis/drug therapy/genetics/pathology ; Protein Kinase Inhibitors/pharmacology/therapeutic use ; }, abstract = {Synchronous malignant mesothelioma (MM) and lung carcinoma are extremely rare in patients without a history of asbestos exposure and poses tremendous difficulties in clinical management. We report a patient without asbestos exposure diagnosed with MM during EGFR-TKI treatment of lung adenocarcinoma (LUAD), who responded to first-line chemotherapy with pemetrexed plus carboplatin and failed to subsequent systemic therapy. Clinicians should be careful about the possibility of MM comorbidity in LUAD patients whose lesions respond differently to EGFR-TKI, even in those without a history of asbestos exposure.}, } @article {pmid33635114, year = {2021}, author = {Hoton, D and Luyckx, M and Galant, C and Dano, H}, title = {Hibernoma-like Changes and TFE3 Expression in Mesothelioma Mimicking TFE3-Translocation Renal Cell Carcinoma: A Diagnostic Pitfall.}, journal = {International journal of surgical pathology}, volume = {29}, number = {6}, pages = {627-630}, doi = {10.1177/1066896921998000}, pmid = {33635114}, issn = {1940-2465}, mesh = {Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/analysis/genetics/*metabolism ; Biomarkers, Tumor/analysis/genetics/*metabolism ; Carcinoma, Renal Cell/diagnosis/pathology ; Female ; Humans ; Kidney Neoplasms/diagnosis/pathology ; Lipoma/diagnosis/pathology ; Mesothelioma/*diagnosis/genetics/secondary ; Middle Aged ; Peritoneal Neoplasms/*diagnosis/genetics/secondary ; Peritoneum/pathology ; Translocation, Genetic ; }, abstract = {The long delay between asbestos exposure and the development of mesothelioma will likely result in an increased incidence of mesothelioma in our industrialized societies. Radiation therapy is another factor known to induce these tumors. We describe a rare case of foamy looking mesothelioma in a 63-year-old patient with a long oncology history of a supposed peritoneal carcinomatosis. The pathologist was faced with a diagnostic pitfall as this peritoneal clear cell tumor expressed transcription factor binding to immunoglobulin heavy constant mu enhancer 3 (TFE3) at the nuclear level. Fortunately, the pathologist performed an extensive panel of immunomarkers, leading to a final diagnosis of epithelioid mesothelioma. Thus, we describe the first case of mesothelioma expressing TFE3. Note that there was no rearrangement of TFE3 in fluorescence in situ hybridization.}, } @article {pmid33624546, year = {2021}, author = {Rossi, G and Caroli, G and Caruso, D and Stella, F and Davoli, F}, title = {Pseudocarcinomatous Mesothelioma: A Hitherto Unreported Presentation closely simulating primary lung cancer.}, journal = {International journal of surgical pathology}, volume = {29}, number = {7}, pages = {775-779}, doi = {10.1177/1066896921997559}, pmid = {33624546}, issn = {1940-2465}, mesh = {Adenocarcinoma of Lung/*diagnosis ; Aged ; Diagnosis, Differential ; Humans ; Lung/diagnostic imaging ; Lung Neoplasms/*diagnosis ; Male ; Mesothelioma, Malignant/*diagnosis/pathology ; Pleura/diagnostic imaging/*pathology ; Pleural Neoplasms/*diagnosis/pathology ; }, abstract = {Malignant mesothelioma (MM) has a wide range of clinical, radiologic, and pathologic presentations, mimicking lung cancer or interstitial lung diseases when predominantly involving the lung parenchyma. The case herein refers to a 79-year-old man, active smoker without asbestos exposure, incidentally discovered to have a pulmonary nodule in the right upper lobe (1.5 cm). The lesion was misinterpreted as primary lung adenocarcinoma at the frozen section in light of the predominant lepidic growth pattern. Definitive examination confirmed neoplastic proliferation along alveolar structures. However, the unusual globous shape of tumor cells along the alveoli abruptly merging with normal pneumocytes prompted us to perform some immunostains that surprisingly revealed a mesothelial differentiation (positive staining with calretinin, cytokeratins (CK5/6), D2-40, and negativity with BRCA-associated protein 1 (BAP1), Thyroid Transcription Factor 1 [TTF-1], claudin-4, carcinoembryonic antigen [CEA], and napsin). MM represents the pathologic counterpart of so-called pseudomesotheliomatous carcinoma, since it appears as a localized pulmonary neoplastic nodule displaying a predominant lepidic growth pattern (pseudocarcinomatous mesothelioma). The challenging diagnostic features of this unique case and a review of similar cases in the literature are discussed.}, } @article {pmid33622366, year = {2021}, author = {Baur, X and Frank, AL}, title = {Ongoing downplaying of the carcinogenicity of chrysotile asbestos by vested interests.}, journal = {Journal of occupational medicine and toxicology (London, England)}, volume = {16}, number = {1}, pages = {6}, pmid = {33622366}, issn = {1745-6673}, abstract = {Industries that mine, manufacture and sell asbestos or asbestos-containing products have a long tradition of promoting the use of asbestos, while placing the burden of economic and health costs on workers and society. This has been successfully done in recent years and decades in spite of the overwhelming evidence that all asbestos types are carcinogenic and cause asbestosis. In doing so, the asbestos industry has undermined the WHO campaign to reach a worldwide ban of asbestos and to eliminate asbestos-related diseases. Even worse, in recent years they succeeded in continuing asbestos mining and consuming in the range of about 1.3 million tons annually. Nowadays, production takes place predominantly in Russia, Kazakhstan and China. Chrysotile is the only asbestos type still sold and represents 95% of asbestos traded over the last century.The asbestos industry, especially its PR agency, the International Chrysotile Association, ICA, financed by asbestos mining companies in Russia, Kazakhstan and Zimbabwe and asbestos industrialists in India and Mexico, continues to be extremely active by using slogans such as chrysotile can be used safely.Another approach of the asbestos industry and of some of its insurance agencies is to broadly defeat liability claims of asbestos victims.In doing so they systematically use inappropriate science produced by their own and/or by industry-affiliated researchers. Some of the latter were also engaged in producing defense material for other industries including the tobacco industry. Frequent examples of distributing such disinformation include questioning or denying established scientific knowledge about adverse health effects of asbestos. False evidence continues to be published in scientific journals and books.The persisting strong influence of vested asbestos-related interests in workers and public health issues including regulations and compensation necessitate ongoing alertness, corrections and appropriate reactions in scientific as well as public media and policy advisory bodies.}, } @article {pmid33617892, year = {2021}, author = {Ierardi, AM and Urban, A and Marsh, GM}, title = {A quantitative weight of evidence assessment of Hill's guidelines for causal inference for cosmetic talc as a cause of mesothelioma.}, journal = {Toxicology and applied pharmacology}, volume = {417}, number = {}, pages = {115461}, doi = {10.1016/j.taap.2021.115461}, pmid = {33617892}, issn = {1096-0333}, mesh = {Animals ; Causality ; Humans ; Mesothelioma/*chemically induced/diagnosis/epidemiology ; Pleural Neoplasms/*chemically induced/diagnosis/epidemiology ; Probability ; Risk Assessment ; Risk Factors ; Talc/*adverse effects ; Time Factors ; Toxicity Tests ; }, abstract = {Cosmetic talc has been suggested to cause mesothelioma. To assess a potential causal relationship between cosmetic talc and mesothelioma, a quantitative weight of evidence analysis was performed in accordance with Hill's nine original guidelines for causal inference using a published empirical model to weight each respective guideline. Various epidemiological, toxicological, and exposure studies related to cosmetic talc and risk of mesothelioma were included in an evaluation of each of Hill's guidelines. Probabilities that the guidelines were true were assigned based on expert judgment. We applied a sensitivity analysis to evaluate the variability of our probability estimates. The overall probability of causality for cosmetic talc and mesothelioma was approximately 1.29% (range: 0.73%-3.96%). This low probability of causality supports the conclusion that cosmetic talc is not related to the development of mesothelioma.}, } @article {pmid33614517, year = {2021}, author = {Cheng, YY and Yuen, ML and Jin, H}, title = {Editorial: Epigenetic Modifications in Mesothelioma.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {650136}, doi = {10.3389/fonc.2021.650136}, pmid = {33614517}, issn = {2234-943X}, } @article {pmid33614198, year = {2021}, author = {Pestak, CR and Boyce, TW and Myers, OB and Hopkins', LO and Wiggins, CL and Wissore, BR and Sood, A and Cook, LS}, title = {A Population-Based Feasibility Study of Occupation and Thoracic Malignancies in New Mexico.}, journal = {Southwest journal of pulmonary & critical care}, volume = {22}, number = {1}, pages = {23-25}, pmid = {33614198}, issn = {2160-6773}, support = {KL2 RR031976/RR/NCRR NIH HHS/United States ; P30 CA118100/CA/NCI NIH HHS/United States ; UL1 TR000041/TR/NCATS NIH HHS/United States ; HHSN261201800014I/CA/NCI NIH HHS/United States ; U01 GM132175/GM/NIGMS NIH HHS/United States ; UL1 TR001449/TR/NCATS NIH HHS/United States ; HHSN261201800014C/CA/NCI NIH HHS/United States ; }, abstract = {BACKGROUND: Occupational exposures in mining and oil/gas extraction are known risk factors for thoracic malignancies (TMs). Given the relatively high proportion of these industries in New Mexico (NM), we conducted a feasibility study of adult lifetime occupational history among TM cases. We hypothesized a higher proportion of occupational TM in NM relative to the estimated national average of 10-14%.

METHODS: We identified incident TM cases through the population-based New Mexico Tumor Registry (NMTR), from 2017-2018. Cases completed a telephone interview. An adjudication panel reviewed case histories and classified cancers as probable, possible, or non-occupational related, taking into account the presence, duration, and latency of exposures. We characterized recruitment and describe job titles and exposures among those with occupational TMs. We also compared the distributions of industry between those with and without occupational TM.

RESULTS: The NMTR identified 400 eligible TM cases, 290 of which were available to be recruited (n=285 lung/bronchial cancer; n=5 mesotheliomas). Of the latter, 60% refused and 18% were deceased, 9% had invalid addresses, 11% were unable to be reached by telephone, and 3% were too ill to participate. The 43 cases who completed an interview held 236 jobs. A total of 33% of cases were classified as probable occupational TM and 5% as possible occupational TM.

CONCLUSIONS: High rates of early mortality and refusals were significant barriers to study participation. Nonetheless, the proportion of probable occupational TMs greatly exceeded the estimated national average, highlighting the need for further study of occupational TM in the state.}, } @article {pmid33577225, year = {2022}, author = {Malpica, A and Euscher, ED and Marques-Piubelli, ML and Miranda, RN and Fournier, KF and Raghav, KP and Ramalingam, P}, title = {Malignant Peritoneal Mesothelioma Associated With Endometriosis: A Clinicopathologic Study of 15 Cases.}, journal = {International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists}, volume = {41}, number = {1}, pages = {59-67}, doi = {10.1097/PGP.0000000000000762}, pmid = {33577225}, issn = {1538-7151}, mesh = {Adolescent ; Adult ; Aged ; Cohort Studies ; Cytoreduction Surgical Procedures ; Endometriosis/complications/*pathology/surgery ; Female ; Germ-Line Mutation ; Humans ; Immunohistochemistry ; Mesothelioma, Malignant/complications/*pathology/surgery ; Middle Aged ; Peritoneal Neoplasms/complications/*pathology/surgery ; Peritoneum/pathology/surgery ; Young Adult ; }, abstract = {Only a few cases of malignant peritoneal mesothelioma (MPeM) associated with endometriosis have been published; with chronic inflammation of the peritoneum associated with the latter being postulated as an inducing factor in the pathogenesis of this tumor. We assessed the clinicopathologic characteristics of MPeM associated with endometriosis to determine if there were other factors besides inflammation that may contribute to the pathogenesis in this patient population. Fifteen MPeM associated with endometriosis were retrieved from our files. Most presented with abdominal/pelvic pain, mass or distention; median age was 45 yr. Only 16% of patients had a history of asbestos exposure. In contrast, a third of the patients had a personal history of other neoplasms, and >80% had a family history of malignancies. Although most tumors had gross and microscopic features typical of MPeM, some had confounding features including "adhesion-like" appearance or gelatinous cysts/nodules, and signet ring cells. Tumors were epithelioid (9) and biphasic (6). MPeM was misdiagnosed as Müllerian carcinoma in 40% of cases. All patients (n=15) had cytoreductive surgery in addition to other therapies. Only 2/12 patients died of disease (17%). The 3- and 5-yr overall survival was 90%. MPeM associated with endometriosis tends to occur in patients with personal/familial history of malignancies, which may be a predisposing factor. In light of this finding, the role of endometriosis in the pathogenesis of MPeM is likely less relevant. The favorable outcome seen in these patients may be related to germline mutations or the hormonal milieu and needs further investigation.}, } @article {pmid33574130, year = {2021}, author = {Sato, T and Mukai, S and Ikeda, H and Mishiro-Sato, E and Akao, K and Kobayashi, T and Hino, O and Shimono, W and Shibagaki, Y and Hattori, S and Sekido, Y}, title = {Silencing of SmgGDS, a Novel mTORC1 Inducer That Binds to RHEBs, Inhibits Malignant Mesothelioma Cell Proliferation.}, journal = {Molecular cancer research : MCR}, volume = {19}, number = {5}, pages = {921-931}, doi = {10.1158/1541-7786.MCR-20-0637}, pmid = {33574130}, issn = {1557-3125}, mesh = {Adaptor Proteins, Signal Transducing/*metabolism ; Animals ; Cell Proliferation/physiology ; Cytoskeletal Proteins/*metabolism ; Female ; Guanine Nucleotide Exchange Factors/*metabolism ; HEK293 Cells ; HeLa Cells ; Humans ; Mechanistic Target of Rapamycin Complex 1/*metabolism ; Mesothelioma, Malignant/*genetics/pathology ; Mice ; Mice, Nude ; Ras Homolog Enriched in Brain Protein/*metabolism ; }, abstract = {Malignant mesothelioma (MM) is an aggressive tumor that typically develops after a long latency following asbestos exposure. Although mechanistic target of rapamycin complex 1 (mTORC1) activation enhances MM cell growth, the mTORC1 inhibitor everolimus has shown limited efficacy in clinical trials of MM patients. We explored the mechanism underlying mTORC1 activation in MM cells and its effects on cell proliferation and progression. Analysis of the expression profiles of 87 MMs from The Cancer Genome Atlas revealed that 40 samples (46%) displayed altered expression of RPTOR (mTORC1 component) and genes immediately upstream that activate mTORC1. Among them, we focused on RHEB and RHEBL1, which encode direct activators of mTORC1. Exogenous RHEBL1 expression enhanced MM cell growth, indicating that RHEB-mTORC1 signaling acts as a pro-oncogenic cascade. We investigated molecules that directly activate RHEBs, identifying SmgGDS as a novel RHEB-binding protein. SmgGDS knockdown reduced mTORC1 activation and inhibited the proliferation of MM cells with mTORC1 activation. Interestingly, SmgGDS displayed high binding affinity with inactive GDP-bound RHEBL1, and its knockdown reduced cytosolic RHEBL1 without affecting its activation. These findings suggest that SmgGDS retains GDP-bound RHEBs in the cytosol, whereas GTP-bound RHEBs are localized on intracellular membranes to promote mTORC1 activation. We revealed a novel role for SmgGDS in the RHEB-mTORC1 pathway and its potential as a therapeutic target in MM with aberrant mTORC1 activation. IMPLICATIONS: Our data showing that SmgGDS regulates RHEB localization to activate mTORC1 indicate that SmgGDS can be used as a new therapeutic target for MM exhibiting mTORC1 activation.}, } @article {pmid33567673, year = {2021}, author = {Keller, M and Reis, K and Hjerpe, A and Dobra, K and Aspenström, P}, title = {Cytoskeletal Organization Correlates to Motility and Invasiveness of Malignant Mesothelioma Cells.}, journal = {Cancers}, volume = {13}, number = {4}, pages = {}, pmid = {33567673}, issn = {2072-6694}, support = {CAN 2017/527//Cancerfonden/ ; CAN 2015/479//Cancerfonden/ ; Beslut 2017/160(180)//Stiftelsen Olle Engkvist Byggmästare/ ; }, abstract = {Malignant mesothelioma (MM) is a rare but highly aggressive cancer that primarily originates from the pleura, peritoneum or pericardium. There is a well-established link between asbestos exposure and progression of MM. Direct invasion of the surrounding tissues is the main feature of MM, which is dependent on dysregulated communication between the mesothelium and the microenvironment. This communication is dependent on the dynamic organization of the cytoskeleton. We have analyzed the organization and function of key cytoskeletal components in MM cell lines of increasing malignancies measured as migratory and invasive properties, and we show that highly malignant and invasive MM cells have an organization of the actin filament and vimentin systems that is distinct from the less malignant MM cell lines. In addition, the Hippo tumor suppressor pathway was inactivated in the invasive MM cells, which was seen as increased YAP nuclear localization.}, } @article {pmid33567623, year = {2021}, author = {Lococo, F}, title = {Malignant Pleural Mesothelioma: Time Is Running Out.}, journal = {Journal of clinical medicine}, volume = {10}, number = {4}, pages = {}, pmid = {33567623}, issn = {2077-0383}, abstract = {Malignant pleural mesothelioma (MPM) is a rare but highly malignant disease of the pleura usually related to asbestos exposure [...].}, } @article {pmid33562413, year = {2021}, author = {Emmett, EA}, title = {Asbestos in High-Risk Communities: Public Health Implications.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {4}, pages = {}, pmid = {33562413}, issn = {1660-4601}, support = {P30 ES013508/ES/NIEHS NIH HHS/United States ; P42 ES023720/ES/NIEHS NIH HHS/United States ; }, mesh = {*Asbestos/toxicity ; Female ; Humans ; Italy ; *Lung Neoplasms ; *Mesothelioma/epidemiology/etiology ; Montana ; *Occupational Exposure ; Pennsylvania ; Public Health ; Turkey ; Western Australia/epidemiology ; }, abstract = {Asbestos-related diseases (ARDs)-mesothelioma, lung cancer, and asbestosis-are well known as occupational diseases. As industrial asbestos use is eliminated, ARDs within the general community from para-occupational, environmental, and natural exposures are more prominent. ARD clusters have been studied in communities including Broni, Italy; Libby, Montana; Wittenoom, Western Australia; Karain, Turkey; Ambler, Pennsylvania; and elsewhere. Community ARDs pose specific public health issues and challenges. Community exposure results in higher proportions of mesothelioma in women and a younger age distribution than occupational exposures. Exposure amount, age at exposure, fiber type, and genetic predisposition influence ARD expression; vulnerable groups include those with social and behavioral risk, exposure to extreme events, and genetic predispositions. To address community exposure, regulations should address all carcinogenic elongated mineral fibers. Banning asbestos mining, use, and importation will not reduce risks from asbestos already in place. Residents of high-risk communities are characteristically exposed through several pathways differing among communities. Administrative responsibility for controlling environmental exposures is more diffuse than for workplaces, complicated by diverse community attitudes to risk and prevention and legal complexity. The National Mesothelioma Registries help track the identification of communities at risk. High-risk communities need enhanced services for screening, diagnosis, treatment, and social and psychological support, including for retired asbestos workers. Legal settlements could help fund community programs. A focus on prevention, public health programs, particularization to specific community needs, and participation is recommended.}, } @article {pmid33562138, year = {2021}, author = {Vogl, M and Rosenmayr, A and Bohanes, T and Scheed, A and Brndiar, M and Stubenberger, E and Ghanim, B}, title = {Biomarkers for Malignant Pleural Mesothelioma-A Novel View on Inflammation.}, journal = {Cancers}, volume = {13}, number = {4}, pages = {}, pmid = {33562138}, issn = {2072-6694}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive disease with limited treatment response and devastating prognosis. Exposure to asbestos and chronic inflammation are acknowledged as main risk factors. Since immune therapy evolved as a promising novel treatment modality, we want to reevaluate and summarize the role of the inflammatory system in MPM. This review focuses on local tumor associated inflammation on the one hand and systemic inflammatory markers, and their impact on MPM outcome, on the other hand. Identification of new biomarkers helps to select optimal patient tailored therapy, avoid ineffective treatment with its related side effects and consequently improves patient's outcome in this rare disease. Additionally, a better understanding of the tumor promoting and tumor suppressing inflammatory processes, influencing MPM pathogenesis and progression, might also reveal possible new targets for MPM treatment. After reviewing the currently available literature and according to our own research, it is concluded that the suppression of the specific immune system and the activation of its innate counterpart are crucial drivers of MPM aggressiveness translating to poor patient outcome.}, } @article {pmid33555117, year = {2021}, author = {Miyagawa, C and Takaya, H and Sakai, K and Nishio, K and Konishi, M and Minamiguchi, S and Shimada, T and Matsumura, N}, title = {A Novel Malignant Peritoneal Mesothelioma with STRN Exon 2 and ALK Exon 20: A Case Report and Literature Review.}, journal = {The oncologist}, volume = {26}, number = {5}, pages = {356-361}, pmid = {33555117}, issn = {1549-490X}, mesh = {Adolescent ; Anaplastic Lymphoma Kinase/genetics ; Calmodulin-Binding Proteins/genetics ; Exons/genetics ; Female ; Gene Rearrangement ; Humans ; Membrane Proteins/genetics ; *Mesothelioma, Malignant ; Nerve Tissue Proteins/genetics ; Oncogene Proteins, Fusion/genetics ; *Peritoneal Neoplasms/drug therapy/genetics ; }, abstract = {Recently, several malignant peritoneal mesotheliomas (MPMs), occurring in young women without asbestos exposure and with fusion genes such as anaplastic lymphoma kinase (ALK) and Ewing sarcoma breakpoint region 1, have been reported. In the present case, we encountered MPM with STRN-ALK fusion in a 17-year-old female adolescent. The case did not respond to chemotherapy and is currently in a clinical trial of alectinib. This is the fourth reported case of MPM with STRN-ALK fusion. Of the 45 cancer cases with STRN-ALK fusion in which the fusion partners were examined, all cases except for the current case showed fusion of exon 3 of STRN and exon 20 of ALK. This is the first case with fusion of exon 2 of STRN and exon 20 of ALK. Further advances in cancer genomic medicine may help clarify the clinical significance of this new fusion. KEY POINTS: Malignant peritoneal mesotheliomas (MPMs) can occur in young women without asbestos exposure and show fusion genes that activate anaplastic lymphoma kinase (ALK) by gene rearrangement. ALK rearrangement and the fusion partner can be detected by companion diagnostics and by next generation sequencing. Patients with MPMs with ALK rearrangement may benefit from target therapy.}, } @article {pmid33544514, year = {2021}, author = {Franko, A and Goricar, K and Dodic Fikfak, M and Kovac, V and Dolzan, V}, title = {The role of polymorphisms in glutathione-related genes in asbestos-related diseases.}, journal = {Radiology and oncology}, volume = {55}, number = {2}, pages = {179-186}, pmid = {33544514}, issn = {1581-3207}, mesh = {Aged ; Asbestos/toxicity ; Asbestosis/*genetics ; Cross-Sectional Studies ; Female ; Genotype ; Glutamate-Cysteine Ligase/genetics ; Glutathione/*genetics ; Glutathione S-Transferase pi/genetics ; Glutathione Transferase/genetics ; Humans ; Male ; Mesothelioma, Malignant/*genetics ; Middle Aged ; Pleural Diseases/*genetics ; *Polymorphism, Genetic ; Regression Analysis ; Smoking/epidemiology ; }, abstract = {BACKGROUND: The study investigated the influence of GCLC, GCLM, GSTM1, GSTT1 and GSTP1 polymorphisms, as well as the influence of interactions between polymorphism and interactions between polymorphisms and asbestos exposure, on the risk of developing pleural plaques, asbestosis and malignant mesothelioma (MM).

SUBJECTS AND METHODS: The cross sectional study included 940 asbestos-exposed subjects, among them 390 subjects with pleural plaques, 147 subjects with asbestosis, 225 subjects with MM and 178 subjects with no asbestos-related disease. GCLC rs17883901, GCLM rs41303970, GSTM1 null, GSTT1 null, GSTP1 rs1695 and GSTP1 rs1138272 genotypes were determined using PCR based methods. In statistical analysis, logistic regression was used.

RESULTS: GSTT1 null genotype was associated with the decreased risk for pleural plaques (OR = 0.63; 95% CI = 0.40-0.98; p = 0.026) and asbestosis (OR = 0.51; 95% CI = 0.28-0.93; p = 0.028), but not for MM. A positive association was found between GSTP1 rs1695 AG + GG vs. AA genotypes for MM when compared to pleural plaques (OR = 1.39; 95% CI = 1.00-1.94; p = 0.049). The interactions between different polymorphisms showed no significant influence on the risk of investigated asbestos-related diseases. The interaction between GSTT1 null polymorphism and asbestos exposure decreased the MM risk (OR = 0.17; 95% CI = 0.03-0.85; p = 0.031).

CONCLUSIONS: Our findings suggest that GSTT1 null genotype may be associated with a decreased risk for pleural plaques and asbestosis, may modify the association between asbestos exposure and MM and may consequently act protectively on MM risk. This study also revealed a protective effect of the interaction between GSTP1 rs1695 polymorphism and asbestos exposure on MM risk.}, } @article {pmid33540554, year = {2021}, author = {De Rienzo, A and Coleman, MH and Yeap, BY and Severson, DT and Wadowski, B and Gustafson, CE and Jensen, RV and Chirieac, LR and Richards, WG and Bueno, R}, title = {Association of RERG Expression with Female Survival Advantage in Malignant Pleural Mesothelioma.}, journal = {Cancers}, volume = {13}, number = {3}, pages = {}, pmid = {33540554}, issn = {2072-6694}, support = {P30 CA006516/CA/NCI NIH HHS/United States ; RO1CA120528//National Cancer Research Institute/ ; }, abstract = {Sex differences in incidence, prognosis, and treatment response have been described for many cancers. In malignant pleural mesothelioma (MPM), a lethal disease associated with asbestos exposure, men outnumber women 4 to 1, but women consistently live longer than men following surgery-based therapy. This study investigated whether tumor expression of genes associated with estrogen signaling could potentially explain observed survival differences. Two microarray datasets of MPM tumors were analyzed to discover estrogen-related genes associated with survival. A validation cohort of MPM tumors was selected to balance the numbers of men and women and control for competing prognostic influences. The RAS like estrogen regulated growth inhibitor (RERG) gene was identified as the most differentially-expressed estrogen-related gene in these tumors and predicted prognosis in discovery datasets. In the sex-matched validation cohort, low RERG expression was significantly associated with increased risk of death among women. No association between RERG expression and survival was found among men, and no relationship between estrogen receptor protein or gene expression and survival was found for either sex. Additional investigations are needed to elucidate the molecular mechanisms underlying this association and its sex specificity.}, } @article {pmid33538989, year = {2021}, author = {Nadal, E and Bosch-Barrera, J and Cedrés, S and Coves, J and García-Campelo, R and Guirado, M and López-Castro, R and Ortega, AL and Vicente, D and de Castro-Carpeño, J}, title = {SEOM clinical guidelines for the treatment of malignant pleural mesothelioma (2020).}, journal = {Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico}, volume = {23}, number = {5}, pages = {980-987}, pmid = {33538989}, issn = {1699-3055}, mesh = {Antineoplastic Agents/therapeutic use ; Asbestos/toxicity ; Carcinogens/toxicity ; Combined Modality Therapy/methods ; Cytoreduction Surgical Procedures ; Deoxycytidine/analogs & derivatives/therapeutic use ; Genetic Testing ; High-Throughput Nucleotide Sequencing ; Humans ; Immunotherapy/methods ; Medical Oncology ; Mesothelioma, Malignant/*diagnosis/etiology/pathology/*therapy ; Neoplasm Staging ; Pemetrexed/therapeutic use ; Platinum Compounds/therapeutic use ; Pleural Neoplasms/*diagnosis/etiology/pathology/*therapy ; Radiotherapy/methods ; Societies, Medical ; Spain ; Vinorelbine/therapeutic use ; Gemcitabine ; }, abstract = {Mesothelioma is a rare and aggressive tumour with dismal prognosis arising in the pleura and associated with asbestos exposure. Its incidence is on the rise worldwide. In selected patients with early-stage MPM, a maximal surgical cytoreduction in combination with additional antitumour treatment may be considered in selected patients assessed by a multidisciplinary tumor board. In patients with unresectable or advanced MPM, chemotherapy with platinum plus pemetrexed is the standard of care. Currently, no standard salvage therapy has been approved yet, but second-line chemotherapy with vinorelbine or gemcitabine is commonly used. Novel therapeutic approaches based on dual immunotherapy or chemotherapy plus immunotherapy demonstrated promising survival benefit and will probably be incorporated in the future.}, } @article {pmid33537296, year = {2020}, author = {Rossini, M and Martini, F and Torreggiani, E and Fortini, F and Aquila, G and Sega, FVD and Patergnani, S and Pinton, P and Maniscalco, P and Cavallesco, G and Rizzo, P and Tognon, M}, title = {Metformin Induces Apoptosis and Inhibits Notch1 in Malignant Pleural Mesothelioma Cells.}, journal = {Frontiers in cell and developmental biology}, volume = {8}, number = {}, pages = {534499}, pmid = {33537296}, issn = {2296-634X}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive asbestos-related cancer arising from the mesothelial cells lining the pleural cavity. MPM is characterized by a silent clinical progression and a highly resistance to conventional chemo/radio-therapies. MPM patients die in a few months/years from diagnosis. Notch signaling is a well-conserved cell communication system, which regulates many biological processes. In humans, the dysregulation of Notch pathway potentially contributes to cancer onset/progression, including MPM. Metformin is the first-line drug used to treat type 2 diabetes mellitus. Metformin is proven to be an effective antitumor drug in preclinical models of different types of cancer. To date, clinical efficacy is being studied in many clinical trials. In this study, the anti-proliferative effect of metformin on MPM cells and the putative involvement of Notch1 as a mediator of metformin activities, were investigated. MPM cells showed high levels of Notch1 activation compared to normal pleural mesothelial cells. Furthermore, metformin treatment hampered MPM cell proliferation and enhanced the apoptotic process, accompanied by decreased Notch1 activation.}, } @article {pmid33533198, year = {2021}, author = {Fukui, T and Okubo, T and Tanimoto, N and Okuma, H and Shiina, Y and Kohama, M and Yamada, J and Funada, Y and Ikura, Y}, title = {Malignant pleural mesothelioma in a patient with pneumothorax: A cumbersome subtype both clinically and pathologically.}, journal = {Thoracic cancer}, volume = {12}, number = {6}, pages = {974-977}, pmid = {33533198}, issn = {1759-7714}, mesh = {Female ; Humans ; Mesothelioma, Malignant/*complications/pathology ; Middle Aged ; Pleural Neoplasms/*complications/pathology ; Pneumothorax/*etiology/physiopathology ; }, abstract = {Here, we report a case of malignant pleural mesothelioma (MPM) that was very difficult to diagnose. A 62-year-old woman with a surgical history of recurrent bilateral pneumothorax was admitted to our hospital with severe dysphagia. Computed tomography (CT) detected stenosis in the lower esophagus. Immunohistochemical examination of a biopsy sample from the stenotic region was suggestive of MPM. Chemotherapy was initiated, but the patient soon weakened and died. Autopsy revealed atypical cells, identical to those seen in the biopsy sample which had spread into the stenotic esophagus and entire thoracic cavity. Although neither pleural thickening/nodules nor asbestos bodies were observed, we finally diagnosed the tumor as a biphasic-type MPM. We re-examined previous surgical specimens of pneumothorax and acknowledged foci of bland mesothelial cell proliferation which had the same pathological findings as tumor cells at autopsy. The lack of asbestos exposure and pleural thickening, an initial manifestation of pneumothorax, and faint cytological atypia prevented an early diagnosis. In cases of recurrent pneumothorax in elderly patients, MPM should be included in the differential diagnosis.}, } @article {pmid33533181, year = {2021}, author = {Piro, R and Fontana, M and Livrieri, F and Menzella, F and Casalini, E and Taddei, S and De Giorgi, F and Facciolongo, N}, title = {Pleural mesothelioma: When echo-endoscopy (EUS-B-FNA) leads to diagnosis in a minimally invasive way.}, journal = {Thoracic cancer}, volume = {12}, number = {6}, pages = {981-984}, pmid = {33533181}, issn = {1759-7714}, mesh = {Endoscopic Ultrasound-Guided Fine Needle Aspiration/*methods ; Female ; Humans ; Mesothelioma/*diagnostic imaging ; Middle Aged ; Pleural Neoplasms/*diagnostic imaging ; }, abstract = {Malignant pleural mesothelioma (MPM) is an asbestos-related and locally invasive tumor with poor prognosis. The acquisition of histological material is mandatory in order to establish a diagnosis. In this situation, the sampling of tissue is generally performed via a thoracoscopic pleural biopsy, either medically or surgically. The use of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) or transesophageal fine needle aspiration with an EBUS scope (EUS-B-FNA) of pleural lesions have only rarely been reported due to the theoretical limitations of tissue acquisition in such cases. We herein report a rare case of MPM successfully diagnosed via EUS-B-FNA in a 49-year-old woman with an unusual presentation characterized by solid thickening in the right mediastinal pleura.}, } @article {pmid33533080, year = {2021}, author = {Dell, LD and Gallagher, AE and Yost, LJ and Mundt, KA}, title = {Integration of Evidence on Community Cancer Risks from Elongate Mineral Particles in Silver Bay, Minnesota.}, journal = {Risk analysis : an official publication of the Society for Risk Analysis}, volume = {41}, number = {9}, pages = {1674-1692}, pmid = {33533080}, issn = {1539-6924}, mesh = {*Environmental Exposure ; Humans ; Minerals/*toxicity ; Minnesota ; Neoplasms/*chemically induced ; Risk Factors ; }, abstract = {The potential for cancer-related risks to community members from ambient exposure to elongate mineral particles (EMPs) in taconite processing has not been formally evaluated. We evaluated 926 ambient air samples including 12,928 EMPs (particle structures with length-to-width ratio ≥3:1) collected over 26 years near a taconite processing facility in Silver Bay, Minnesota. Eighty-two percent of EMPs were ≤3 μm in length and 97% of EMPs had an average aspect ratio <20:1. A total of 935 (7.3%) EMPs had length >5 μm and AR ≥3:1. Average ambient concentration of NIOSH countable amphibole EMPs over all years was 0.000387 EMPs per cubic centimeter (EMP/cm[3]). Of 12,765 nonchrysotile EMPs, the number of amphiboles with length and width dimensions that correlate best with asbestos-related carcinogenicity ranged from four (0.03%) to 13 (0.1%) and the associated ambient amphibole air concentrations ranged from 0.000003 to 0.000007 EMP/cm[3] . After 65 years of taconite processing in Silver Bay, evidence of an increased risk of mesothelioma and lung cancer in community members who did not work in the taconite industry is lacking. The absence of an increased risk of asbestos-related cancer in the Silver Bay community is coherent with supporting evidence from epidemiological and toxicological studies, as well as ambient exposure data and lake sediment data collected in Minnesota Iron Range communities. Collectively, the data provide consistent evidence that nonasbestiform amphibole minerals lack the carcinogenic potential exhibited by amphibole asbestos.}, } @article {pmid33515502, year = {2021}, author = {Nowak, AK}, title = {New and old treatments for malignant mesothelioma: not just immunotherapy.}, journal = {The Lancet. Respiratory medicine}, volume = {9}, number = {6}, pages = {547-549}, doi = {10.1016/S2213-2600(20)30516-6}, pmid = {33515502}, issn = {2213-2619}, mesh = {Deoxycytidine/analogs & derivatives ; Humans ; Immunotherapy ; *Mesothelioma, Malignant ; *Pleural Neoplasms/drug therapy ; Gemcitabine ; }, } @article {pmid33509005, year = {2021}, author = {Cook, AM and McDonnell, A and Millward, MJ and Creaney, J and Hasani, A and McMullen, M and Meniawy, T and Robinson, BWS and Lake, RA and Nowak, AK}, title = {A phase 1b clinical trial optimizing regulatory T cell depletion in combination with platinum-based chemotherapy in thoracic cancers.}, journal = {Expert review of anticancer therapy}, volume = {21}, number = {5}, pages = {465-474}, doi = {10.1080/14737140.2021.1882308}, pmid = {33509005}, issn = {1744-8328}, mesh = {Antineoplastic Combined Chemotherapy Protocols ; *Carcinoma, Non-Small-Cell Lung/drug therapy ; Cisplatin ; Cyclophosphamide/administration & dosage/toxicity ; Humans ; *Lung Neoplasms/drug therapy ; Pemetrexed ; Platinum/therapeutic use ; T-Lymphocytes, Regulatory ; }, abstract = {Background: Single-agent cyclophosphamide can deplete regulatory T-cells (Treg). We aimed to determine optimal dosing and scheduling of oral cyclophosphamide, alongside pemetrexed-based chemotherapy, to deplete Treg in mesothelioma or non-small-cell lung cancer patients.Methods: 31 Patients received pemetrexed ± cisplatin or carboplatin on day 1 of a 21-day cycle (maximum 6 cycles). From cycle two, patients received cyclophosphamide, 50 mg/day, with intrapatient escalation to maximum 100/150 mg/day alternately. Immunological changes were examined by flow cytometry. Primary endpoint was Treg proportion of CD4[+] T-cells, with doses tailored to target Treg nadir <4%.Results: Reduction in Treg proportion was observed on day 8 of all cycles, and was not augmented by cyclophosphamide. Few patients achieved the <4% Treg target. Treg proliferation reached nadir one week after chemotherapy, and peaked on day 1 of the subsequent cycle. Efficacy parameters were similar to chemotherapy alone. Seventeen percent of patients ceased cyclophosphamide due to toxicity.Conclusions: Specific Treg depletion to the degree seen with single-agent cyclophosphamide was not observed during pemetrexed-based chemotherapy. This study highlights the poor evidence basis for use of cyclophosphamide as an immunotherapeutic in combination with chemotherapy, and the importance of detailed flow cytometry studies.Trial registration: Clinical trial registration: www.anzctr.org.au identifier is ACTRN12609000260224.}, } @article {pmid33506658, year = {2020}, author = {Barone Adesi, F and Bruno, C and Calisti, R and Chellini, E and Comba, P and Consonni, D and Fazzo, L and Fedeli, U and Forastiere, F and Magnani, C and Marinaccio, A and Merler, E and Mirabelli, D and Ricci, P and Terracini, B}, title = {[Effects of Asbestos on Human Health. Document of the Italian Epidemiological Association (AIE)].}, journal = {Epidemiologia e prevenzione}, volume = {44}, number = {5-6}, pages = {327-338}, doi = {10.19191/EP20.5-6.A001.064}, pmid = {33506658}, issn = {1120-9763}, mesh = {*Asbestos/toxicity ; *Asbestosis/epidemiology/etiology ; Carcinogens/toxicity ; Humans ; Italy/epidemiology ; Lung Neoplasms/epidemiology/etiology ; Mesothelioma/epidemiology/etiology ; Occupational Exposure/statistics & numerical data ; }, abstract = {OBJECTIVES: the Italian Epidemiological Association (AIE) intends to formulate assessments and recommendations on the most relevant and critical aspects in the preparation, conduct, and interpretation of epidemiological investigations on the health effects of exposure to asbestos and asbestos-like fibres.

the document was prepared by a working group of AIE associates, with a broad curriculum of epidemiological investigations, starting from the evaluation of scientific evidence, and was subsequently evaluated by the AIE governing body.

RESULTS: the topics covered included: • consumption and presence of asbestos; • association between asbestos exposure and disease; • epidemiological surveillance of asbestos related diseases in Italy; • risk function for asbestos related diseases; • increased risk and anticipation of the disease; • interaction between asbestos and other carcinogens; • diagnosis in epidemiological studies; • assessment of exposure to asbestos; • epidemiological evidence on asbestos related diseases.

CONCLUSIONS: the document ends with a summary of the conclusions of scientific research shared by AIE, with reflection on the methodology to be followed for the application at individual level of the results of epidemiological studies, and the proposal of themes on which to direct research.}, } @article {pmid33502280, year = {2021}, author = {Ringgaard Petersen, T and Panou, V and Meristoudis, C and Weinreich, UM and Røe, OD}, title = {Clinical prognostic factors in pleural mesothelioma: best supportive care and anti-tumor treatments in a real-life setting.}, journal = {Acta oncologica (Stockholm, Sweden)}, volume = {60}, number = {4}, pages = {521-527}, doi = {10.1080/0284186X.2021.1876246}, pmid = {33502280}, issn = {1651-226X}, mesh = {Female ; Humans ; *Lung Neoplasms/therapy ; *Mesothelioma/therapy ; *Pleural Neoplasms/drug therapy ; Prognosis ; Retrospective Studies ; }, abstract = {BACKGROUND: This study aims to investigate patient- and disease characteristics associated with survival in malignant pleural mesothelioma (MPM) patients with anti-tumor treatment or with best supportive care (BSC).

MATERIALS AND METHODS: Consecutive MPM cases diagnosed in North Denmark Region from 1972 to 2015 were reevaluated and verified by two pathologists using modern immunohistochemical techniques. Danish registries and hospital records were used to gather patient-, asbestos exposure-, and disease information.

RESULTS: Of the 279 patients, anti-tumor treatment was administered to 184 patients (66.0%). All of those received chemotherapy alone or as part of a multimodal treatment, where pemetrexed was given to 126 (68.5%) patients. Asbestos exposure was documented in 92.5% of all patients. In the treated group, mean age was lower (66 years versus 74 years, p < 0.01), rate of occupational asbestos exposure was higher (74.5 versus 54.7%, p < 0.01), more patients had better performance score (98.4 versus 60%, p < 0.01) and stage was lower (81 versus 63.2%, p < 0.01) compared to the BSC group. Multivariate analysis showed that epithelioid subtype was the only common prognostic factor for OS in both groups. In BSC patients, good PS and female gender was associated with improved OS. Median overall survival (OS) was 17 versus 4 months (p < 0.01), and independently of the histopathological subtype, the median and 2-year survival was higher in the treated versus the BSC group (p < 0.02).

CONCLUSIONS: This retrospective study showed that epithelioid subtype is the only independent positive prognostic factor of survival in treated patients with MPM. For BSC patients, the epithelioid subtype, good PS, and female gender were positive prognostic factors, while age and comorbidities were not significant. This study with long-term follow-up of treated and BSC MPM patients can contribute to the clinical stratification of patients. Further validation is appropriate to verify these findings.}, } @article {pmid33498425, year = {2021}, author = {Kwak, K and Zoh, KE and Paek, D}, title = {Incidence of Cancer and Asbestos-Related Diseases among Residents Living near Abandoned Asbestos Mines in South Korea: A Retrospective Cohort Study Using National Health Insurance Database.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {3}, pages = {}, pmid = {33498425}, issn = {1660-4601}, mesh = {*Asbestos/toxicity ; Humans ; Incidence ; Male ; *Mesothelioma ; National Health Programs ; *Occupational Exposure ; Republic of Korea/epidemiology ; Retrospective Studies ; }, abstract = {The use of asbestos has been banned since 2009 in South Korea. However, there is still a risk of exposure to environmental asbestos originating from abandoned asbestos mines. We constructed a retrospective dynamic cohort using the National Health Insurance Database of South Korea. We determined the risk of developing asbestos-related diseases (ARDs) among residents living near asbestos mines compared with those living in the control area and the general population. The risks of asbestosis (adjusted hazards ratio [HR] 65.40, 95% CI = 35.02-122.12) and pleural plaques (adjusted HR 3.55, 95% CI = 1.96-6.41) were significantly increased among residents living near the asbestos mines compared with the control area. The risk of malignant mesothelioma was increased near asbestos mines compared with the control area; however, it was not significant (adjusted HR 1.83, 95% CI = 0.61-5.47). When a separate analysis according to sex was conducted, the risk of mesothelioma among male residents was statistically significant (adjusted HR 8.30, 95% CI = 1.04-66.63), and the standardized incidence ratio (SIR) was significantly increased (SIR 3.48, 95% CI = 1.50-6.85). The risk of ARDs was increased due to environmental asbestos exposure near abandoned asbestos mines in South Korea.}, } @article {pmid33472960, year = {2021}, author = {Asciak, R and George, V and Rahman, NM}, title = {Update on biology and management of mesothelioma.}, journal = {European respiratory review : an official journal of the European Respiratory Society}, volume = {30}, number = {159}, pages = {}, pmid = {33472960}, issn = {1600-0617}, support = {MCCC-RP-14-A17178/MCCC_/Marie Curie/United Kingdom ; }, mesh = {*Asbestos/adverse effects ; Biology ; Humans ; *Mesothelioma/diagnosis/genetics/therapy ; *Mesothelioma, Malignant ; *Pleural Neoplasms/diagnosis/epidemiology/etiology ; }, abstract = {Malignant pleural mesothelioma is an aggressive, incurable cancer that is usually caused by asbestos exposure several decades before symptoms arise. Despite widespread prohibition of asbestos production and supply, its incidence continues to increase. It is heterogeneous in its presentation and behaviour, and diagnosis can be notoriously difficult. Identification of actionable gene mutations has proven challenging and current treatment options are largely ineffective, with a median survival of 10-12 months.However, the past few years have witnessed major advances in our understanding of the biology and pathogenesis of mesothelioma. This has also revealed the limitations of existing diagnostic algorithms and identified new treatment targets.Recent clinical trials have re-examined the role of surgery, provided new options for the management of associated pleural effusions and heralded the addition of targeted therapies. The increasing complexity of mesothelioma management, along with a desperate need for further research, means that a multidisciplinary team framework is essential for the delivery of contemporary mesothelioma care.This review provides a synthesised overview of the current state of knowledge and an update on the latest research in the field.}, } @article {pmid33466653, year = {2021}, author = {Marcq, E and Van Audenaerde, JRM and De Waele, J and Merlin, C and Pauwels, P and van Meerbeeck, JP and Fisher, SA and Smits, ELJ}, title = {The Search for an Interesting Partner to Combine with PD-L1 Blockade in Mesothelioma: Focus on TIM-3 and LAG-3.}, journal = {Cancers}, volume = {13}, number = {2}, pages = {}, pmid = {33466653}, issn = {2072-6694}, support = {141433//Agentschap voor Innovatie door Wetenschap en Technologie/ ; 11455//Kom op tegen Kanker/ ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive cancer that is causally associated with previous asbestos exposure in most afflicted patients. The prognosis of patients remains dismal, with a median overall survival of only 9-12 months, due to the limited effectiveness of any conventional anti-cancer treatment. New therapeutic strategies are needed to complement the limited armamentarium against MPM. We decided to focus on the combination of different immune checkpoint (IC) blocking antibodies (Abs). Programmed death-1 (PD-1), programmed death ligand-1 (PD-L1), T-cell immunoglobulin mucin-3 (TIM-3), and lymphocyte activation gene-3 (LAG-3) blocking Abs were tested as monotherapies, and as part of a combination strategy with a second IC inhibitor. We investigated their effect in vitro by examining the changes in the immune-related cytokine secretion profile of supernatant collected from treated allogeneic MPM-peripheral blood mononuclear cell (PBMC) co-cultures. Based on our in vitro results of cytokine secretion, and flow cytometry data that showed a significant upregulation of PD-L1 on PBMC after co-culture, we chose to further investigate the combinations of anti PD-L1 + anti TIM-3 versus anti PD-L1 + anti LAG-3 therapies in vivo in the AB1-HA BALB/cJ mesothelioma mouse model. PD-L1 monotherapy, as well as its combination with LAG-3 blockade, resulted in in-vivo delayed tumor growth and significant survival benefit.}, } @article {pmid33466544, year = {2021}, author = {Mensi, C and Dallari, B and Polonioli, M and Riboldi, L and Consonni, D and Pesatori, AC}, title = {Mesothelioma in Agriculture in Lombardy, Italy: An Unrecognized Risk.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {1}, pages = {}, pmid = {33466544}, issn = {1660-4601}, mesh = {Aged ; Aged, 80 and over ; *Agriculture ; *Asbestos/toxicity ; Female ; Humans ; Italy/epidemiology ; Male ; *Mesothelioma/chemically induced/epidemiology ; Middle Aged ; *Occupational Exposure ; }, abstract = {Cohort studies showed consistently low risks for malignant mesothelioma (MM) among agricultural workers, however the investigated exposures did not include asbestos. Our aim is to describe sources of asbestos exposure of MM in agriculture. Twenty-six MM cases in agricultural or seed trades workers were identified through the MM registry of the Lombardy region, Italy in 2000-2016. Asbestos exposures were investigated through a standardized questionnaire. The most frequent exposure circumstances were recycled jute bags previously containing asbestos (11 cases) and maintenance and repair of asbestos roofs (12 subjects). Three subjects performed maintenance and repair of tractor asbestos brakes and two used asbestos filters for wine production. Our data suggest asbestos exposure opportunities in the agricultural setting, underlining the need to look for this exposure in subjects affected with mesothelioma.}, } @article {pmid33465294, year = {2021}, author = {Eccher, A and Girolami, I and Lucenteforte, E and Troncone, G and Scarpa, A and Pantanowitz, L}, title = {Diagnostic mesothelioma biomarkers in effusion cytology.}, journal = {Cancer cytopathology}, volume = {129}, number = {7}, pages = {506-516}, doi = {10.1002/cncy.22398}, pmid = {33465294}, issn = {1934-6638}, mesh = {Biomarkers, Tumor/*analysis ; Homozygote ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Mesothelioma, Malignant/*diagnosis/genetics/*metabolism/pathology ; Pleural Effusion/genetics/*metabolism/*pathology ; Tumor Suppressor Proteins/analysis ; Ubiquitin Thiolesterase/analysis ; }, abstract = {Malignant mesothelioma is a rare malignancy with a poor prognosis whose development is related to asbestos fiber exposure. An increasing role of genetic predisposition has been recognized recently. Pleural biopsy is the gold standard for diagnosis, in which the identification of pleural invasion by atypical mesothelial cell is a major criterion. Pleural effusion is usually the first sign of disease; therefore, a cytological specimen is often the initial or the only specimen available for diagnosis. Given that reactive mesothelial cells may show marked atypia, the diagnosis of mesothelioma on cytomorphology alone is challenging. Accordingly, cell block preparation is encouraged, as it permits immunohistochemical staining. Traditional markers of mesothelioma such as glucose transporter 1 (GLUT1) and insulin-like growth factor 2 mRNA-binding protein 3 (IMP3) are informative, but difficult to interpret when reactive proliferations aberrantly stain positive. BRCA1-associated protein 1 (BAP1) nuclear staining loss is highly specific for mesothelioma, but sensitivity is low in sarcomatoid tumors. Cyclin-dependent kinase inhibitor 2A (CDKN2A)/p16 homozygous deletion, assessed by fluorescence in situ hybridization, is more specific for mesothelioma with better sensitivity, even in the sarcomatoid variant. The surrogate marker methylthioadenosine phosphorylase (MTAP) has been found to demonstrate excellent diagnostic correlation with p16. The purpose of this review is to provide an essential appraisal of the literature regarding the diagnostic value of many of these emerging biomarkers for malignant mesothelioma in effusion cytology.}, } @article {pmid36034504, year = {2021}, author = {Noda, R and Yanagisawa, S and Inoue, M and Hara, T}, title = {A case of brain metastasis with pathological transformation of long-surviving malignant pleural mesothelioma: illustrative case.}, journal = {Journal of neurosurgery. Case lessons}, volume = {1}, number = {3}, pages = {CASE2099}, pmid = {36034504}, issn = {2694-1902}, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare cancer, and in 80% of cases the cause is asbestos exposure. In 1972, the World Health Organization (WHO) declared asbestos is a carcinogenic substance. Since then, every developed country has restricted and banned the product. Because of its high heat resistance, asbestos had been widely used as building material for decades. The WHO estimated that approximately 125 million people are exposed to asbestos, and more than 107,000 die from asbestos-related diseases annually. Because of its long incubation period, the number of patients is estimated to keep increasing in the near future.

OBSERVATIONS: The authors report a case of long-surviving MPM with a rushed clinical course after brain metastasis. A 69-year-old woman diagnosed with MPM (epithelial type) 6 years earlier presented with a brain metastasis. The pathological result of the brain metastasis was the sarcomatoid type. This case showed the possibility of subtype transition after long survival.

LESSONS: This article aids in understanding the long-term natural history of MPM and the possibility of epithelial-mesenchymal transition. Neurosurgeons have to be aware of its the natural history and the possibility of brain metastasis.}, } @article {pmid33438079, year = {2021}, author = {Borrelli, EP and McGladrigan, CG}, title = {A Review of Pharmacologic Management in the Treatment of Mesothelioma.}, journal = {Current treatment options in oncology}, volume = {22}, number = {2}, pages = {14}, pmid = {33438079}, issn = {1534-6277}, mesh = {Antineoplastic Agents/administration & dosage/adverse effects/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use ; Biomarkers, Tumor ; Clinical Decision-Making ; Combined Modality Therapy ; Disease Management ; Disease Susceptibility ; Drug Development ; Humans ; Mesothelioma/diagnosis/*drug therapy/epidemiology/etiology ; Standard of Care ; Treatment Outcome ; }, abstract = {Mesothelioma is a rare and severe form of cancer that is associated with asbestos exposure. Approximately 2500 Americans die annually from this condition with a median survival of 1 year. The latency period of this disease ranges anywhere from 20 to 70 years, with shorter latency periods associated with a higher exposure intensity to asbestos. Therefore, cases of mesothelioma are expected in the coming decades. This highlights the need for clinicians to understand the pharmacologic regimens available for treating this rare, yet serious malignancy. With multiple treatment regimens available in the treatment of this condition, clinicians should take an evidence-based approach and consider the totality of evidence and safety information while considering the best patient-centered approach for treatment. This article provides a review of current pharmacologic treatment options available for mesothelioma and goes into detail about the recommended medication regimens and dosages and the available evidence of efficacy, effectiveness, and/or safety and estimates the annual cost of treatment for these medications on the U.S. healthcare system per patient. A brief introduction is provided for several promising agents currently under investigation for mesothelioma as well.}, } @article {pmid33435788, year = {2022}, author = {Germine, M and Puffer, JH}, title = {Anthophyllite asbestos from Staten Island, New York: Longitudinal fiber splitting.}, journal = {Archives of environmental & occupational health}, volume = {77}, number = {4}, pages = {268-275}, doi = {10.1080/19338244.2021.1873095}, pmid = {33435788}, issn = {2154-4700}, mesh = {*Asbestos ; Asbestos, Amphibole/analysis ; Humans ; *Mesothelioma/chemically induced/epidemiology ; New York ; }, abstract = {Asbestos ore was sampled from a historical anthophyllite mine in Staten Island, New York. High-resolution transmission electron microscopy (HRTEM) was used to image the structure of nineteen fibers of the anthophyllite asbestos. The anthophyllite was characterized by a high level of chain width disorder, involving wide chain multiplicity faults (CMFs) that were frequent in fibers, randomly spaced, and ranged from one to eight chains in width. This chain width disorder was manifest by streaking of electron diffraction rows of chain width. The anthophyllite asbestos fibers were found to be produced by longitudinal splitting rather than crystal growth. Such splitting is a function of cleavage along CMFs rather than crystal boundaries. The morphology of the fibers is consistent with anthophyllite asbestos mined in Finland associated with lung cancer and mesothelioma. These findings may have regulatory implications.}, } @article {pmid33422732, year = {2021}, author = {Ejegi-Memeh, S and Darlison, L and Moylan, A and Tod, A and Sherborne, V and Warnock, C and Taylor, BH}, title = {Living with mesothelioma: A qualitative study of the experiences of male military veterans in the UK.}, journal = {European journal of oncology nursing : the official journal of European Oncology Nursing Society}, volume = {50}, number = {}, pages = {101889}, doi = {10.1016/j.ejon.2020.101889}, pmid = {33422732}, issn = {1532-2122}, mesh = {Adaptation, Psychological ; Adult ; Aged ; Aged, 80 and over ; Asbestos/toxicity ; Family/psychology ; Female ; Humans ; Life Change Events ; Male ; Mesothelioma/nursing/*psychology ; Middle Aged ; Military Personnel/psychology ; Qualitative Research ; Self-Help Groups ; United Kingdom ; Veterans/*psychology ; }, abstract = {PURPOSE: The UK has the highest incidence of mesothelioma in the world. Evidence in the United States suggests that mesothelioma may disproportionately affect military veterans. However, there has been no investigation of the experience of UK veterans living with mesothelioma. The Military Mesothelioma Experience Study (MiMES) aimed to understand the experience and health/support needs of British Armed Forces personnel/veterans with mesothelioma.

METHODS: Semi-structured interviews were conducted with 13 veterans living with mesothelioma, and nine family members of veterans living with mesothelioma. Participants were recruited via charities and asbestos support groups. Data were analysed using thematic analysis.

RESULTS: Participants' experiences are presented using three themes, i) exposure to asbestos and awareness of asbestos related diseases, ii) using military strategies to cope with mesothelioma and iii) preferences for information and support. MiMES indicates that the nature and range of UK military veterans' asbestos exposure is varied and not limited to high risk occupations. Participants' knowledge of asbestos and experience of mesothelioma influenced their experiences of diagnosis. Participants had coping strategies influenced by their military experiences. Assistance in navigating health and military systems was considered beneficial, especially if support was provided by professionals with knowledge or experience of the military. Attributes which may inhibit veterans from seeking professional support are discussed.

CONCLUSION: MiMES provides insight into how UK military veterans experience and cope with mesothelioma. Key implications focus on the role that Mesothelioma Nurse Specialists, Asbestos Support Groups and veterans groups play in providing acceptable support for UK veterans.}, } @article {pmid33419364, year = {2020}, author = {Affatato, R and Mendogni, P and Del Gobbo, A and Ferrero, S and Ricci, F and Broggini, M and Rosso, L}, title = {Establishment and Characterization of Patient-Derived Xenografts (PDXs) of Different Histology from Malignant Pleural Mesothelioma Patients.}, journal = {Cancers}, volume = {12}, number = {12}, pages = {}, pmid = {33419364}, issn = {2072-6694}, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a very aggressive tumor originating from mesothelial cells. Although several etiological factors were reported to contribute to MPM onset, environmental exposure to asbestos is certainly a major risk factor. The latency between asbestos (or asbestos-like fibers) exposure and MPM onset is very long. MPM continues to be a tumor with poor prognosis despite the introduction of new therapies including immunotherapy. One of the major problems is the low number of preclinical models able to recapitulate the features of human tumors. This impacts the possible discovery of new treatments and combinations.

METHODS: In this work, we aimed to generate patient-derived xenografts (PDXs) from MPM patients covering the three major histotypes (epithelioid, sarcomatoid, and mixed) occurring in the clinic. To do this, we obtained fresh tumors from biopsies or pleurectomies, and samples were subcutaneously implanted in immunodeficient mice within 24 h.

RESULTS: We successfully isolated different PDXs and particularly concentrated our efforts on three covering the three histotypes. The tumors that grew in mice compared well histologically with the tumors of origin, and showed stable growth in mice and a low response to cisplatin, as was observed in the clinic.

CONCLUSIONS: These models are helpful in testing new drugs and combinations that, if successful, could rapidly translate to the clinical setting.}, } @article {pmid33414743, year = {2020}, author = {Granieri, A and Bonafede, M and Marinaccio, A and Iavarone, I and Marsili, D and Franzoi, IG}, title = {SARS-CoV-2 and Asbestos Exposure: Can Our Experience With Mesothelioma Patients Help Us Understand the Psychological Consequences of COVID-19 and Develop Interventions?.}, journal = {Frontiers in psychology}, volume = {11}, number = {}, pages = {584320}, pmid = {33414743}, issn = {1664-1078}, abstract = {Since its emergence, the novel coronavirus disease of 2019 (COVID-19) has had enormous physical, social, and psychological impacts worldwide. The aim of this article was to identify elements of our knowledge on asbestos exposure and malignant mesothelioma (MM) that can provide insight into the psychological impact of the COVID-19 pandemic and be used to develop adequate interventions. Although the etiology of Covid-19 and MM differs, their psychological impacts have common characteristics: in both diseases, there is a feeling of being exposed through aerial contagion to an "invisible killer" without boundaries that can strike even the strongest individuals. In both cases, affected persons can experience personality dysfunction, anxiety, depression, and posttraumatic symptoms; helplessness, hopelessness, and projection of destructive thoughts onto external forces often emerge, while defense mechanisms such as denial, splitting, repression, and reduced emotional expression are used by individuals to contain their overwhelming anxieties. We believe that in both diseases, an integrated multidimensional intervention offered by hospitals and other public health services is the most effective approach to alleviating patients' and caregivers' psychological distress. In particular, we emphasize that in the context of both MM and COVID-19, Brief Psychoanalytic Group therapy can help patients and caregivers attribute meaning to the significant changes in their lives related to the experience of the disease and identify adaptive strategies and more realistic relational modalities to deal with what has happened to them. We also highlight the importance of developing a surveillance system that includes individual anamnestic evaluation of occupational risk factors for COVID-19 disease.}, } @article {pmid33414260, year = {2021}, author = {Gunatilake, S and Lodge, D and Neville, D and Jones, T and Fogg, C and Bassett, P and Begum, S and Kerley, S and Marshall, L and Glaysher, S and Elliott, S and Stores, R and Bishop, L and Chauhan, A}, title = {Predicting survival in malignant pleural mesothelioma using routine clinical and laboratory characteristics.}, journal = {BMJ open respiratory research}, volume = {8}, number = {1}, pages = {}, pmid = {33414260}, issn = {2052-4439}, mesh = {Humans ; Laboratories ; *Lung Neoplasms/diagnosis ; *Mesothelioma/diagnosis ; *Mesothelioma, Malignant ; *Pleural Neoplasms/diagnosis ; Retrospective Studies ; }, abstract = {INTRODUCTION: The prognosis of malignant pleural mesothelioma (MPM) is poor, with a median survival of 8-12 months. The ability to predict prognosis in MPM would help clinicians to make informed decisions regarding treatment and identify appropriate research opportunities for patients. The aims of this study were to examine associations between clinical and pathological information gathered during routine care, and prognosis of patients with MPM, and to develop a 6-month mortality risk prediction model.

METHODS: A retrospective cohort study of patients diagnosed with MPM at Queen Alexandra Hospital, Portsmouth, UK between December 2009 and September 2013. Multivariate analysis was performed on routinely available histological, clinical and laboratory data to assess the association between different factors and 6-month survival, with significant associations used to create a model to predict the risk of death within 6 months of diagnosis with MPM.

RESULTS: 100 patients were included in the analysis. Variables significantly associated with patient survival in multivariate analysis were age (HR 1.31, 95% CI 1.09 to 1.56), smoking status (current smoker HR 3.42, 95% CI 1.11 to 4.20), chest pain (HR 2.14, 95% CI 1.23 to 3.72), weight loss (HR 2.13, 95% CI 1.18 to 3.72), platelet count (HR 1.05, 95% CI 1.00 to 1.10), urea (HR 2.73, 95% CI 1.31 to 5.69) and adjusted calcium (HR 1.47, 95% CI 1.10 to 1.94). The resulting risk model had a c-statistic value of 0.76. A Hosmer-Lemeshow test confirmed good calibration of the model against the original dataset.

CONCLUSION: Risk of death at 6 months in patients with a confirmed diagnosis of MPM can be predicted using variables readily available in clinical practice. The risk prediction model we have developed may be used to influence treatment decisions in patients with MPM. Further validation of the model requires evaluation of its performance on a separate dataset.}, } @article {pmid33400741, year = {2020}, author = {Reis, K and Arbiser, JL and Hjerpe, A and Dobra, K and Aspenström, P}, title = {Inhibitors of cytoskeletal dynamics in malignant mesothelioma.}, journal = {Oncotarget}, volume = {11}, number = {50}, pages = {4637-4647}, pmid = {33400741}, issn = {1949-2553}, abstract = {Malignant mesotheliomas (MMs) are highly aggressive mesenchymal tumors that originate from mesothelial cells lining serosal cavities; i.e., the pleura, peritoneum, and pericardium. Classically, there is a well-established link between asbestos exposure, oxidative stress, release of reactive oxygen species, and chronic inflammatory mediators that leads to progression of MMs. MMs have an intermediate phenotype, with co-expression of mesenchymal and epithelial markers and dysregulated communication between the mesothelium and the microenvironment. We have previously shown that the organization and function of key cytoskeletal components can distinguish highly invasive cell lines from those more indolent. Here, we used these tools to study three different types of small-molecule inhibitors, where their common feature is their influence on production of reactive oxygen species. One of these, imipramine blue, was particularly effective in counteracting some key malignant properties of highly invasive MM cells. This opens a new possibility for targeted inhibition of MMs based on well-established molecular mechanisms.}, } @article {pmid33399341, year = {2021}, author = {Argani, P and Lian, DWQ and Agaimy, A and Metzler, M and Wobker, SE and Matoso, A and Epstein, JI and Sung, YS and Zhang, L and Antonescu, CR}, title = {Pediatric Mesothelioma With ALK Fusions: A Molecular and Pathologic Study of 5 Cases.}, journal = {The American journal of surgical pathology}, volume = {45}, number = {5}, pages = {653-661}, pmid = {33399341}, issn = {1532-0979}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; P50 CA140146/CA/NCI NIH HHS/United States ; P50 CA217694/CA/NCI NIH HHS/United States ; }, mesh = {Abdominal Neoplasms/enzymology/*genetics/pathology ; Adolescent ; Anaplastic Lymphoma Kinase/*genetics ; Biomarkers, Tumor/analysis/*genetics ; Child ; Female ; *Gene Fusion ; *Gene Rearrangement ; Genetic Predisposition to Disease ; Humans ; Immunohistochemistry ; Male ; Mesothelioma/enzymology/*genetics/pathology ; Molecular Diagnostic Techniques ; Testicular Neoplasms/enzymology/*genetics/pathology ; }, abstract = {Pediatric mesotheliomas are rare and their pathogenesis remains undefined. In this study, we report 5 cases of malignant mesothelioma in children, characterized by fusions involving the anaplastic lymphoma kinase (ALK) gene. Four cases occurred in females involving the abdominal cavity and were characterized by a pure epithelioid morphology. The fifth arose in the tunica vaginalis of a 15-year-old male and displayed a biphasic epithelioid-sarcomatoid phenotype. All cases demonstrated the classic morphologic and immunohistochemical features of malignant mesothelioma, including tubulopapillary architecture and cuboidal epithelioid cells with eosinophilic cytoplasm and uniform nuclei with vesicular chromatin. Immunohistochemically, all cases showed labeling for ALK, cytokeratins, WT1, and calretinin, while lacking expression of adenocarcinoma immunomarkers. Four cases demonstrated weak-moderate labeling for PAX8 protein, which resulted in diagnostic challenges with primary peritoneal serous carcinoma. The ALK genetic abnormalities were investigated by a combination of molecular methods. Archer FusionPlex was performed in 2 cases, showing fusions between ALK with either STRN or TPM1 genes, resulting in a transcript that retained the ALK kinase domain. One case was further studied by DNA targeted sequencing, but no additional genetic alterations were observed. In 1 case, cytogenetic analysis showed the presence of a t(2;15)(p23;q22) and fluorescence in situ hybridization confirmed the ALK gene break-apart. In the remaining 2 cases, ALK gene rearrangements were demonstrated by fluorescence in situ hybridization. Unlike adult mesotheliomas, which are tightly linked to asbestos exposure, often show loss of BAP1 expression and have complex karyotypes, ALK-rearranged mesothelioma appears to be similar to other fusion-positive mesotheliomas, such as those harboring EWSR1/FUS-ATF1 fusions, sharing significant morphologic overlap, occurring in young patients and displaying a simple, translocation-driven genetic profile.}, } @article {pmid33388783, year = {2021}, author = {Marinaccio, A and Consonni, D and Mensi, C and Mirabelli, D and Migliore, E and Magnani, C and Di Marzio, D and Gennaro, V and Mazzoleni, G and Girardi, P and Negro, C and Romanelli, A and Chellini, E and Grappasonni, I and Madeo, G and Romeo, E and Ascoli, V and Carrozza, F and Angelillo, IF and Cavone, D and Tumino, R and Melis, M and Curti, S and Brandi, G and Mattioli, S and Iavicoli, S and , }, title = {Authors' response: Mezei et al's "Comments on a recent case-control study of malignant mesothelioma of the pericardium and the tunica vaginalis testis".}, journal = {Scandinavian journal of work, environment & health}, volume = {47}, number = {1}, pages = {87-89}, pmid = {33388783}, issn = {1795-990X}, mesh = {*Asbestos/adverse effects ; Case-Control Studies ; Cohort Studies ; Female ; Humans ; Italy/epidemiology ; Male ; *Mesothelioma/epidemiology ; *Mesothelioma, Malignant ; *Occupational Exposure ; Pericardium ; Testis ; }, abstract = {Mezei et al's letter (1) is an opportunity to provide more details about our study on pericardial and tunica vaginalis testis (TVT) mesothelioma (2), which is based on the Italian national mesothelioma registry (ReNaM): a surveillance system on mesothelioma, with individual asbestos exposure assessment. Incidence of pericardial mesothelioma has been estimated around 0.5 and 0.2 cases per 10 million person-years in men and women, respectively, and around 1 case for TVT mesothelioma. ReNaM collected 138 cases thanks to its long period of observation (1993-2015) and national coverage. Conducting a population-based case-control study with incidence-density sampling of controls across Italy and over a 23 year time-span should have been planned in 1993 and would have been beyond feasibility and ReNaM scope. We rather exploited two existing series of controls (3). The resulting incomplete time- and spatial matching of cases and controls is a limitation of our study and has been acknowledged in our article. The analysis of case-control studies can nevertheless be accomplished in logistic models accounting for the variables of interest, in both individually and frequency matched studies (4). Furthermore, analyses restricted to (i) regions with enrolled controls, (ii) cases with definite diagnosis, (iii) incidence period 2000-2015, and (iv) subjects born before 1950 have been provided in the manuscript, confirming the strength of the association with asbestos exposure (supplemental material tables S4-7). Following Mezei et al's suggestion, we performed further sensitivity analyses by restriction to regions with controls and fitting conditional regression models using risk-sets made of combinations of age and year of birth categories (5-year classes for both). We confirmed positive associations with occupational exposure to asbestos of pericardial mesothelioma, with odds ratios (OR) (adjusted for region) of 9.16 among women [95% confidence interval (CI) 0.56-150] and 5.63 (95% CI 1.02-31.0) among men; for TVT mesothelioma the OR was 7.70 (95% CI 2.89-20.5). Using risk sets of age categories and introducing year of birth (5-year categories) as a covariate (dummy variables) the OR were similar: OR (adjusted for region) of 9.17 among women (95% CI 0.56-150) and 5.76 (95% CI 1.07-31.0) among men; for TVT the OR was 9.86 (95% CI 3.46-28.1). Possible bias from incomplete geographical overlap between cases and controls has been addressed in the paper (table S4) and above. In spatially restricted analyses, OR were larger than in those including cases from the whole country, indicating that bias was towards the null. Mezei et al further noted that "the regional distribution of controls is different from that of person-time observed". This objection is not relevant because the above analyses were adjusted by region. Our controls were provided by a population-based study on pleural mesothelioma (called MISEM) and a hospital-based study on cholangiocarcinoma (called CARA). In MISEM, the response rate was 48.4%, a low but not unexpected rate as participation among population controls is usually lower and has been declining over time (5). It is important to underline that ReNaM applied the same questionnaire that was used for interviews and carried out the same exposure assessment as both MISEM and CARA. As repeatedly stated in ReNaM papers (6-7), each regional operating center assesses asbestos exposure based on the individual questionnaire, other available information, and knowledge of local industries. Occupational exposure to asbestos is classified as definite, probable or possible. Occupational exposure is (i) definite when the subject`s work was reported or otherwise known to have involved the use of asbestos or asbestos-containing materials (MCA); (ii) probable when subjects worked in factories where asbestos or MCA were used, but their personal exposure could not be documented; and (iii) possible when they were employed in industrial activities known to entail the use of asbestos or MCA. Hence, the definite and probable categories are closer to one another and were combined in our analyses. In any case, restricting analyses to subjects with definite occupational exposure and using each set of controls separately, as suggested by Mezei et al, yielded elevated OR for TVT and pericardial mesothelioma among men using both the above described modelling strategies; the OR could not be calculated for women. There were 70 (25 pericardial and 45 TVT) occupationally exposed mesothelioma cases. In population-based studies, analyses by occupation are limited by the low prevalence of most specific jobs. As briefly reported in our paper, for purely descriptive purposes, the industrial activity of exposure (cases may have multiple exposures), were construction (22 exposures, 7 and 15 for pericardial and TVT mesotheliomas, respectively), steel mills and other metal working industries (4 and 11), textile industries (2 and 3), and agriculture (2 and 5); other sectors had lower exposure frequencies. The absence of industries like asbestos-cement production, shipbuilding and railway carriages production/repair should not be surprising and had already been observed (7). In the Italian multicenter cohort study of asbestos workers (8), given the person-years of observation accrued by workers employed in these industries and gender- and site-specific crude incidence rates, approximately 0.1 case of pericardial and 0.2 of TVT mesothelioma would have been expected from 1970 to 2010. Even increasing ten-fold such figures to account for higher occupational risks among these workers would not change much. Asbestos exposure in agriculture has been repeatedly discussed in ReNaM reports (9: pages 70, 73, 128, 164 and 205). Exposure opportunities included the presence of asbestos in wine production, reuse of hessian bags previously containing asbestos, or construction and maintenance of rural buildings. Similarly, mesothelioma cases and agricultural workers exposed to asbestos have been noted in France (10). In conclusion, the additional analyses we performed according to Mezei et al's suggestions confirm the association between asbestos exposure and pericardial and TVT mesothelioma, supporting the causal role of asbestos for all mesotheliomas. ReNaM`s continuing surveillance system with national coverage is a precious platform for launching analytical studies on pleural and extra pleural mesothelioma. References 1. Mezei G, Chang ET, Mowat FS, Moolgavkar SH. Comments on a recent case-control study of malignant mesothelioma of the pericardium and the tunica vaginalis testis Scand J Work Environ Health. 2021;47(1):85-86. https://doi.org/10.5271/3909 2. Marinaccio A, Consonni D, Mensi C, Mirabelli D, Migliore E, Magnani C et al.; ReNaM Working Group. Association between asbestos exposure and pericardial and tunica vaginalis testis malignant mesothelioma: a case-control study and epidemiological remarks. Scand J Work Environ Health. 2020;46(6):609-617. https://doi.org/10.5271/sjweh.3895. 3. Greenland S. Control-initiated case-control studies. Int J Epidemiol 1985 Mar;14(1):130-4. https://doi.org/10.1093/ije/14.1.130. 4. Pearce N. Analysis of matched case-control studies. BMJ 2016 Feb;352:i969. https://doi.org/10.1136/bmj.i969. 5. Bigert C, Gustavsson P, Straif K, Pesch B, Brüning T, Kendzia B et al. Lung cancer risk among cooks when accounting for tobacco smoking: a pooled analysis of case-control studies from Europe, Canada, New Zealand, and China. J Occup Environ Med 2015 Feb;57(2):202-9. https://doi.org/10.1097/JOM.0000000000000337. 6. Marinaccio A, Binazzi A, Marzio DD, Scarselli A, Verardo M, Mirabelli D et al.; ReNaM Working Group. Pleural malignant mesothelioma epidemic: incidence, modalities of asbestos exposure and occupations involved from the Italian National Register. Int J Cancer 2012 May;130(9):2146-54. https://doi.org/10.1002/ijc.26229. 7. Marinaccio A, Binazzi A, Di Marzio D, Scarselli A, Verardo M, Mirabelli D et al. Incidence of extrapleural malignant mesothelioma and asbestos exposure, from the Italian national register. Occup Environ Med 2010 Nov;67(11):760-5. https://doi.org/10.1136/oem.2009.051466. 8. Ferrante D, Chellini E, Merler E, Pavone V, Silvestri S, Miligi L et al.; the working group. Italian pool of asbestos workers cohorts: mortality trends of asbestos-related neoplasms after long time since first exposure. Occup Environ Med 2017 Dec;74(12):887-98. https://doi.org/10.1136/oemed-2016-104100. 9. ReNaM VI Report. Available from: https://www.inail.it/cs/internet/docs/alg-pubbl-registro-nazionale-mesoteliomi-6-rapporto.pdf. Italian 10. Marant Micallef C, Shield KD, Vignat J, Baldi I, Charbotel B, Fervers B et al. Cancers in France in 2015 attributable to occupational exposures. Int J Hyg Environ Health 2019 Jan;222(1):22-9. https://doi.org/10.1016/j.ijheh.2018.07.015.}, } @article {pmid33381446, year = {2020}, author = {Yoshikawa, Y and Kuribayashi, K and Minami, T and Ohmuraya, M and Kijima, T}, title = {Epigenetic Alterations and Biomarkers for Immune Checkpoint Inhibitors-Current Standards and Future Perspectives in Malignant Pleural Mesothelioma Treatment.}, journal = {Frontiers in oncology}, volume = {10}, number = {}, pages = {554570}, pmid = {33381446}, issn = {2234-943X}, abstract = {Malignant pleural mesothelioma (MPM) is strongly associated with occupational or environmental asbestos exposure and arises from neoplastic transformation of mesothelial cells in the pleural cavity. The only standard initial treatment for unresectable MPM is combination chemotherapy with cisplatin (CDDP) and pemetrexed (PEM). Further, CDDP/PEM is the only approved regimen with evidence of prolonged overall survival (OS), although the median OS for patients treated with this regimen is only 12 months after diagnosis. Thus, the development of new therapeutic strategies has been investigated for approximately 20 years. In contrast to recent advances in personalized lung cancer therapies, diagnostic and prognostic biomarker research has just started in mesothelioma. Epigenetic alterations include DNA methylation, histone modifications, and other chromatin-remodeling events. These processes are involved in numerous cellular processes including differentiation, development, and tumorigenesis. Epigenetic modifications play an important role in gene expression and regulation related to malignant MPM phenotypes and histological subtypes. An immune checkpoint PD-1 inhibitor, nivolumab, was approved as second-line therapy for patients who had failed initial chemotherapy, based on the results of the MERIT study. Various clinical immunotherapy trials are ongoing in patients with advanced MPM. In this review, we describe recent knowledge on epigenetic alterations, which might identify candidate therapeutic targets and immunotherapeutic regimens under development for MPM.}, } @article {pmid33380218, year = {2021}, author = {Seastedt, KP and Pruett, N and Hoang, CD}, title = {Mouse models for mesothelioma drug discovery and development.}, journal = {Expert opinion on drug discovery}, volume = {16}, number = {6}, pages = {697-708}, pmid = {33380218}, issn = {1746-045X}, support = {ZIA BC011657/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Animals ; *Asbestos ; Carcinogenesis ; Drug Discovery ; *Lung Neoplasms ; *Mesothelioma/drug therapy ; *Mesothelioma, Malignant ; Mice ; Tumor Microenvironment ; }, abstract = {INTRODUCTION: Mesothelioma is an aggressive mesothelial lining tumor. Available drug therapies include chemotherapeutic agents, targeted molecular therapies, and immune system modulators. Mouse models were instrumental in the discovery and evaluation of such therapies, but there is need for improved understanding of the role of inflammation, tumor heterogeneity, mechanisms of carcinogenesis, and the tumor microenvironment. Novel mouse models may provide new insights and drive drug therapy discovery that improves efficacy.

AREAS COVERED: This review concerns available mouse models for mesothelioma drug discovery and development including the advantages and disadvantages of each. Gaps in current knowledge of mesothelioma are highlighted, and future directions for mouse model research are considered.

EXPERT OPINION: Soon, CRISPR-Cas gene-editing will improve understanding of mesothelioma mechanisms foundational to the discovery and testing of efficacious therapeutic targets. There are at least two likely areas of upcoming methodology development. One is concerned with precise modeling of inflammation - is it a causal process whereby inflammatory signals contribute to tumor initiation, or is it a secondary passenger process driven by asbestos exposure effects? The other area of methods improvement regards the availability of humanized immunocompromised mice harboring patient-derived xenografts. Combining human tumors in an environment with human immune cells will enable rapid innovation in immuno-oncology therapeutics.}, } @article {pmid33379304, year = {2020}, author = {Oddone, E and Bollon, J and Nava, CR and Minelli, G and Imbriani, M and Consonni, D and Marinaccio, A and Magnani, C and Barone-Adesi, F}, title = {Forecast of Malignant Peritoneal Mesothelioma Mortality in Italy up to 2040.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {1}, pages = {}, pmid = {33379304}, issn = {1660-4601}, mesh = {Aged ; Aged, 80 and over ; Female ; Forecasting ; Humans ; Italy/epidemiology ; Male ; Mesothelioma, Malignant/*mortality ; Middle Aged ; Peritoneal Neoplasms/*mortality ; }, abstract = {Despite their differences, pleural and peritoneal mesothelioma are frequently lumped together to describe epidemic curves and to forecast future mesothelioma trends. This study aims to describe the malignant peritoneal mesothelioma (MPeM) epidemic in Italy (1996-2016) and to forecast future trends up to 2040 in order to contribute to the assessment of MPeM future burden. All MPeM deaths in Italy from 1996-2016 were collected (as provided by the Italian National Statistical Institute (ISTAT)) in order to estimate MPeM mortality rates for each 3-year period from 1996 to 2016. Poisson age-period-cohort (APC) models were then used to forecast MPeM future trends. Between 2017 and 2040, 1333 MPeM deaths are expected. The number of MPeM deaths, as well as mortality rates, are expected to constantly decrease throughout the considered period. Based on considering the information from this study, it can be concluded that the MPeM epidemic has probably already reached its peak in Italy.}, } @article {pmid33363966, year = {2020}, author = {Brahim, D and Mechergui, N and Ben Said, H and Cherif, D and Ladhari, N and Youssef, I}, title = {Peritoneal mesothelioma associated with bladder cancer and occupational exposure to asbestos: A case report.}, journal = {Clinical case reports}, volume = {8}, number = {12}, pages = {3529-3532}, pmid = {33363966}, issn = {2050-0904}, abstract = {Mesothelioma is a rare tumor usually located on the pleura. In this typical location, it is closely linked to asbestos exposure. However, in other locations such as in peritoneal mesothelioma, the association to asbestos remains unusual.}, } @article {pmid33347735, year = {2021}, author = {Re, A and Shersher, D and Allen, A and Schwarting, R and Ren, S}, title = {Malignant pleural neoplasm with both differentiation of epithelioid mesothelioma and squamous-cell carcinoma, a rare phenomena.}, journal = {Diagnostic cytopathology}, volume = {49}, number = {6}, pages = {E234-E237}, doi = {10.1002/dc.24686}, pmid = {33347735}, issn = {1097-0339}, mesh = {Aged ; Asbestos/toxicity ; Carcinoma, Squamous Cell/etiology/*pathology ; Cell Differentiation ; Humans ; Male ; Mesothelioma, Malignant/*pathology ; Occupational Exposure/adverse effects ; Pleural Neoplasms/etiology/*pathology ; }, abstract = {Malignant mesothelioma, a neoplasm arising within the serosal surfaces, has been linked closely to asbestos exposure. We present a case of 72-year-old male with a 27 year work-related history of asbestos exposure who presented with dyspnea. Chest computed tomography scan showed a large, right pleural effusion with compressive right lung atelectasis. Biopsies, subsequent pleurectomy and lung wedge resections revealed epithelioid malignant mesothelioma with associated focal non-keratinizing squamous-cell carcinoma, supported by extensive immunohistochemical stains and molecular studies. The patient was treated with 6 cycles of carboplatin/pemetrexed, showing no new metastases. Seven months post-treatment, the patient presented with progressive dyspnea and large pleural effusions. Bilateral pleural fluid was collected and showed malignant epithelioid cells, morphologically similar to the patient's pleural neoplastic cells. However, the tumor was positive for squamous cells markers and showed BAP1 loss, while negative for mesothelial markers. The findings support the diagnosis of squamous-cell carcinoma and were consistent with the patient's previously diagnosed pleural neoplastic origin. A malignant mesothelioma associated with squamous-cell carcinoma is a rare phenonmenon. To our knowledge, only two case reports are available in current literature. This unique case shows a single pleura tumor differentiating as both malignant mesothelioma and squamous-cell carcinoma. Squamous-cell carcinoma is the predominating malignancy seen within the bilateral pleural effusions, a potential pitfall for cytology specimen diagnosis.}, } @article {pmid33346174, year = {2020}, author = {Fazzo, L and Minelli, G and Bruno, C and Comba, P and Conti, S and De Santis, M and Zona, A and Binazzi, A and Magnani, C and Marinaccio, A and Iavarone, I}, title = {Early mortality from malignant mesothelioma in Italy as a proxy of environmental exposure to asbestos in children.}, journal = {Annali dell'Istituto superiore di sanita}, volume = {56}, number = {4}, pages = {478-486}, doi = {10.4415/ANN_20_04_10}, pmid = {33346174}, issn = {2384-8553}, mesh = {Adult ; Aged ; Asbestos/*toxicity ; Child ; Environmental Exposure/*adverse effects ; Female ; Humans ; Italy/epidemiology ; Male ; Mesothelioma, Malignant/*etiology/*mortality ; Middle Aged ; Time Factors ; }, abstract = {Malignant mesothelioma (MM) is a rare neoplasm caused by asbestos. Mortality from MM in ≤50 years old people, considering the long latency, is likely related to asbestos exposure in childhood. Mortality from MM (C45, ICD10 code) is described among ≤50 years (ys) old people in Italy, in 2003-2016. National and regional Standardized Rates (SRs) were computed by age-class. The North-South trend of regional SRs, increasing in >50ys age-class, showed a flat cline in ≤50ys old people. Municipal Standardized Mortality Ratios (SMRs) were computed, with respect to regional figures, for ≤50 ys old population. In Italy, 487 people ≤50 ys old died from MM, in 2003-2016 (2.5% of all MM deaths), corresponding to 35/year. The highest SMRs were observed in Northern Regions, the most industrialized areas. Exceeding SMRs were found in 10 municipalities where former asbestos-cement plants, shipyards, and a quarry contaminated by fluoro-edenite fibres were present. Early mortality from MM, proxy of childhood environmental asbestos exposure, deserves particular concern.}, } @article {pmid33344293, year = {2020}, author = {Chand, MT and Edens, J and Lin, T and Anderson, I and Berri, R}, title = {Benign multicystic peritoneal mesothelioma: literature review and update.}, journal = {Autopsy & case reports}, volume = {10}, number = {3}, pages = {e2020159}, pmid = {33344293}, issn = {2236-1960}, abstract = {Benign multicystic peritoneal mesothelioma (BMPM) is a rare peritoneal tumor diagnosed predominantly in pre-menopausal women. Associated risk factors include endometriosis and pelvic inflammatory disease in women, and prior abdominal surgery in both genders. To date, the pathogenesis of this disease remains controversial with possible etiologies, including a neoplastic versus a reactive process. Given the risk factors, some authors believe that this disease is secondary to a reactive process. However, because some studies describe cases where there is no prior surgical history or inflammatory milieu present, and because of this entity's predilection for recurrence, some authors believe the origin to be neoplastic. Some genetic and familial associations have also been reported. Malignant transformation is extremely rare, with only two cases reported in the literature, despite the recurrence potential. Like the etiology, the name of this entity is also controversial. Some authors prefer the term "peritoneal inclusion cyst (PCM)" instead of "benign cystic mesothelioma" and argue that the term mesothelioma should only be used when there is evidence of atypia. Most cases of BMPM are discovered incidentally. Others reflect sequela of tumor mass effect. It appears intra-operatively as large, multi-focal, cystic lesions in the peritoneal and pelvic cavity. Diagnosis is achieved through surgical sampling with histopathological examination. Immunobiologically, BMPM exhibits multiple small cystic spaces with flattened lining containing calretinin positive cells without atypical features, mitotic figures, or tissue invasion. Treatment includes cytoreductive surgery. Here we present a case of BMPM in a 60-year-old male - a rare disease in an uncommon patient population.}, } @article {pmid33336248, year = {2021}, author = {Bartkowiak, K and Casjens, S and Andreas, A and Ačkar, L and Joosse, SA and Raiko, I and Brüning, T and Geffken, M and Peine, S and Johnen, G and Weber, DG and Pantel, K}, title = {Sensitive Blood-Based Detection of Asbestos-Associated Diseases Using Cysteine-Rich Angiogenic Inducer 61 as Circulating Protein Biomarker.}, journal = {Clinical chemistry}, volume = {67}, number = {2}, pages = {363-373}, doi = {10.1093/clinchem/hvaa232}, pmid = {33336248}, issn = {1530-8561}, mesh = {Aged ; Aged, 80 and over ; Asbestosis/blood/*diagnosis ; Biomarkers/blood ; Case-Control Studies ; Cysteine-Rich Protein 61/*blood ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Male ; Mesothelioma/blood/*diagnosis ; Middle Aged ; Sensitivity and Specificity ; }, abstract = {BACKGROUND: Detection of asbestos-associated diseases like asbestosis or mesothelioma is still challenging. We sought to improve the diagnosis of benign asbestos-associated disease (BAAD) by detection of the protein cysteine-rich angiogenic inducer 61 (Cyr61) in human plasma.

METHODS: Plasma Cyr61 was quantified using an enzyme-linked immunosorbent assay. Plasma samples from males diagnosed with BAAD, but without a malignant disease (n = 101), and malignant mesothelioma (n = 21; 15 males, 6 females), as well as nonasbestos-exposed healthy control participants (n = 150; 58 males, 92 females) were analyzed. Clinical sensitivity and specificity of Cyr61 were determined by receiver operating characteristic analysis.

RESULTS: The median plasma Cyr61 concentration for healthy control participants was 0.27 ng/mL. Cytoplasmic Cyr61 in peripheral blood mononuclear cells from healthy control participants was evenly distributed, as detected by immunofluorescent staining. The increase in plasma Cyr61 concentrations in the BAAD study group was statistically significant compared to the healthy control participants (P < 0.0001). For the detection of BAAD vs male healthy control participants, clinical sensitivity was 88% and clinical specificity 95% with an area under the curve of 0.924 at maximal Youden Index. For a predefined clinical specificity of 100%, the clinical sensitivity was 76%. For male mesothelioma patients vs male healthy control participants, the clinical sensitivity at maximal Youden Index was 95% with a clinical specificity of 100% (area under the curve, 0.997) and for a predefined clinical specificity of 100%, the clinical sensitivity was 93%.

CONCLUSIONS: In our study, plasma Cyr61 protein concentrations showed to be a new biomarker for asbestos-associated diseases like BAAD and mesothelioma in men, which deserves further investigation in large-scale cohort studies.}, } @article {pmid33329908, year = {2020}, author = {Park, EK and Johnson, AR and Wilson, D and Thomas, PS and Yates, DH}, title = {Follow-up of Soluble Mesothelin-Related Protein Levels in Participants With Asbestos-Related Disorders.}, journal = {Safety and health at work}, volume = {11}, number = {4}, pages = {425-430}, pmid = {33329908}, issn = {2093-7911}, abstract = {BACKGROUND: Asbestos exposure is associated with the development of the cancer malignant mesothelioma (MM). Measurement of soluble mesothelin-related protein (SMRP) has been suggested as a method for detection of MM in its early stages. We prospectively examined SMRP levels in participants with asbestos exposure who are a group at a high risk of development of MM.

METHODS: This study was a follow-up of our cohort of 322 asbestos-exposed participants. No further participants developed MM or malignancy over the study period. Mean follow-up time was 22.9 months.

RESULTS: Mean (standard deviation) SMRP levels at baseline and follow-up were 0.94 (0.79) and 0.91 (0.86) nmol/L (p = 0.1033), respectively. Mean SMRP levels of the healthy individuals exposed to asbestos at baseline was significantly lower than those of participants with asbestosis and pleural plaques alone; similar patterns were found on follow-up measurements. There was a statistically significant effect of age on serial SMRP measurements. Our study confirms higher levels in participants with nonmalignant asbestos-related disorders. Levels decreased in asbestos-related disorders other than asbestosis, where a small increase was observed. We did not detect any further cases of malignancy.

CONCLUSION: Monitoring programs for early detection of MM need to take into account increased SMRP levels found in benign asbestos-related diseases.}, } @article {pmid33319489, year = {2021}, author = {Sakai, K and Inoue, M and Mikami, S and Nishimura, H and Kuwabara, Y and Kojima, A and Toda, M and Ogawa-Kobayashi, Y and Kikuchi, S and Hirata, Y and Mikami-Saito, Y and Kyoyama, H and Moriyama, G and Shiibashi, M and Seike, M and Gemma, A and Uematsu, K}, title = {Functional inhibition of heat shock protein 70 by VER-155008 suppresses pleural mesothelioma cell proliferation via an autophagy mechanism.}, journal = {Thoracic cancer}, volume = {12}, number = {4}, pages = {491-503}, pmid = {33319489}, issn = {1759-7714}, support = {16-B-1-22//Saitama Medical University/ ; 18-B-1-19//Saitama Medical University/ ; }, mesh = {Autophagy ; Cell Line, Tumor ; Cell Proliferation ; HSP70 Heat-Shock Proteins/*metabolism ; Humans ; Mesothelioma/*drug therapy/pathology ; Pleural Neoplasms/*drug therapy/pathology ; Purine Nucleosides/pharmacology/*therapeutic use ; Transfection ; }, abstract = {BACKGROUND: Pleural mesothelioma, a devastating asbestos-associated malignancy, urgently requires a novel effective therapy. Heat shock protein 70 (HSP70), which is synthesized in the cell response to protein damage, is expected to be a new target for antitumor treatment. In addition to its well-known protein refolding function, HSP70 regulates cell proliferation through different pathways, including PI3K/AKT/mTOR, and autophagy in malignant cells. In this study, we attempted to clarify the effects of VER-155008, an HSP70 inhibitor, on pleural mesothelioma.

METHODS: Human pleural mesothelioma cell lines 211H, H2452 and H28 were cultured with VER-155008, and protein expression, cell proliferation, colony formation, cell cycle, synergistic effect with cisplatin, and autophagy induction were analyzed.

RESULTS: In mesothelioma cell lines, VER-155008 (5.0 μM or more) inhibited cell growth and colony formation, accompanied by G1 cell cycle arrest. According to western blot analysis, VER-155008 reduced p-AKT expression. However, VER-155008 failed to show a synergistic effect with cisplatin on cell growth. Mesothelioma cells transfected with the novel plasmid pMRX-IP-GFP-LC3-RFP-LC3ΔG, which was developed for the quantitative and statistical estimation of macroautophagy, showed enhanced macroautophagy upon treatment with VER-155008 and gefitinib which is an EGFR-tyrosine kinase inhibitor. In addition, fetal bovine serum deprivation induced macroautophagy was further enhanced by VER-155008.

CONCLUSIONS: On the basis of these results, functional HSP70 inhibition by VER-155008 suppressed cell growth in pleural mesothelioma cells, accompanied by enhanced macroautophagy. HSP70 inhibition is thus expected to become a new strategy for treating mesothelioma.

KEY POINTS: Significant findings of the study In pleural mesothelioma cells, inhibition of HSP70 function by VER-155008 suppressed cell proliferation accompanied by induction of autophagy which was synergistically enhanced under the starvation condition, whereas gefitinib, an EGFR-TKI, did not show the same synergistic effect in autophagy. What this study adds The inhibition of HSP70 induced autophagy and suppressed cell proliferation in mesothelioma cells.}, } @article {pmid33318203, year = {2020}, author = {Bononi, A and Goto, K and Ak, G and Yoshikawa, Y and Emi, M and Pastorino, S and Carparelli, L and Ferro, A and Nasu, M and Kim, JH and Suarez, JS and Xu, R and Tanji, M and Takinishi, Y and Minaai, M and Novelli, F and Pagano, I and Gaudino, G and Pass, HI and Groden, J and Grzymski, JJ and Metintas, M and Akarsu, M and Morrow, B and Hassan, R and Yang, H and Carbone, M}, title = {Heterozygous germline BLM mutations increase susceptibility to asbestos and mesothelioma.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {117}, number = {52}, pages = {33466-33473}, pmid = {33318203}, issn = {1091-6490}, support = {R01 CA198138/CA/NCI NIH HHS/United States ; P20 GM103466/GM/NIGMS NIH HHS/United States ; U01 CA214195/CA/NCI NIH HHS/United States ; P30 CA071789/CA/NCI NIH HHS/United States ; R01 ES030948/ES/NIEHS NIH HHS/United States ; Z01 BC010816/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Adult ; Aged ; Animals ; Asbestos, Crocidolite ; Asbestosis/*genetics ; Family ; Female ; *Genetic Predisposition to Disease ; Genomic Instability ; Germ-Line Mutation/*genetics ; Heterozygote ; Humans ; Incidence ; Inflammation/pathology ; Male ; Mesothelioma/*genetics ; Mice ; Middle Aged ; RecQ Helicases/*genetics ; }, abstract = {Rare biallelic BLM gene mutations cause Bloom syndrome. Whether BLM heterozygous germline mutations (BLM[+/-]) cause human cancer remains unclear. We sequenced the germline DNA of 155 mesothelioma patients (33 familial and 122 sporadic). We found 2 deleterious germline BLM[+/-] mutations within 2 of 33 families with multiple cases of mesothelioma, one from Turkey (c.569_570del; p.R191Kfs*4) and one from the United States (c.968A>G; p.K323R). Some of the relatives who inherited these mutations developed mesothelioma, while none with nonmutated BLM were affected. Furthermore, among 122 patients with sporadic mesothelioma treated at the US National Cancer Institute, 5 carried pathogenic germline BLM[+/-] mutations. Therefore, 7 of 155 apparently unrelated mesothelioma patients carried BLM[+/-] mutations, significantly higher (P = 6.7E-10) than the expected frequency in a general, unrelated population from the gnomAD database, and 2 of 7 carried the same missense pathogenic mutation c.968A>G (P = 0.0017 given a 0.00039 allele frequency). Experiments in primary mesothelial cells from Blm[+/-] mice and in primary human mesothelial cells in which we silenced BLM revealed that reduced BLM levels promote genomic instability while protecting from cell death and promoted TNF-α release. Blm[+/-] mice injected intraperitoneally with asbestos had higher levels of proinflammatory M1 macrophages and of TNF-α, IL-1β, IL-3, IL-10, and IL-12 in the peritoneal lavage, findings linked to asbestos carcinogenesis. Blm[+/-] mice exposed to asbestos had a significantly shorter survival and higher incidence of mesothelioma compared to controls. We propose that germline BLM[+/-] mutations increase the susceptibility to asbestos carcinogenesis, enhancing the risk of developing mesothelioma.}, } @article {pmid33314519, year = {2020}, author = {Kishimoto, T and Fujimoto, N and Mizuhashi, K and Kozawa, S and Miura, M}, title = {Retrospective investigation on diagnostic process for benign asbestos pleural effusion (BAPE) using checklist.}, journal = {Journal of occupational health}, volume = {62}, number = {1}, pages = {e12182}, pmid = {33314519}, issn = {1348-9585}, support = {//The research and development, and the dissemination project/ ; //Japan Organization of Occupational Health and Safety/ ; }, mesh = {Aged ; Aged, 80 and over ; Asbestosis/*diagnosis ; Checklist/*standards ; Diagnosis, Differential ; Humans ; Male ; Middle Aged ; Occupational Diseases/*diagnosis ; Occupational Exposure/analysis ; Pleural Effusion/*diagnosis ; Radiography ; Reproducibility of Results ; Retrospective Studies ; Thoracentesis ; Thoracoscopy ; }, abstract = {OBJECTIVES: In Japan, benign asbestos pleural effusion (BAPE) has been eligible for industrial accident compensation since 2003 as an asbestos-related disease despite the lack of good criteria. We compiled a criteria into a checklist of essential items and for excluding other diseases inducing pleural effusion as a diagnosis process.

METHOD: Thoracentesis was performed in order to confirm the presence of pleural effusion at the initial diagnosis, and 105 suspected BAPE patients were retrospectively examined. We complied a checklist comprising the following diagnostic items: (a) occupational asbestos exposure; (b) confirmation of exudate of pleural effusion; (c) exclusion of pleural effusion with malignant tumors based on negative results of CEA and hyaluronic acid, and cytology of pleural effusion; (d) exclusion of rheumatic, bacterial, and tuberculous pleuritis; (d) radiological findings for exclusion of malignancies; and (e) histopathological findings based on thoracoscopy that exclude malignancies (when thoracoscopy was not performed, there was confirmation that no malignancies were present during 3-month follow-up observation). Cases that satisfied all items were defined as BAPE.

RESULTS: Among the 105 suspected cases, there were five cases that had no occupational asbestos exposure; six cases in which transudate of on pleural effusion; one case each of rheumatoid pleuritis and tuberculous pleuritis; and five cases of pleural mesothelioma based on chest radiography and histopathological findings within 3 months after initial diagnosis. Therefore, we excluded 18 cases from the 105 candidates and determined 87 cases of BAPE.

CONCLUSION: We consider that six items described above are suitable for diagnosing BAPE.}, } @article {pmid33312638, year = {2020}, author = {Moteallemi, A and Minaei, M and Tahmasbizadeh, M and Fadaei, S and Masroor, K and Fanaei, F}, title = {Monitoring of airborne asbestos fibers in an urban ambient air of Mashhad City, Iran: levels, spatial distribution and seasonal variations.}, journal = {Journal of environmental health science & engineering}, volume = {18}, number = {2}, pages = {1239-1246}, pmid = {33312638}, issn = {2052-336X}, abstract = {Asbestos, as with other pollutants in the air, has adverse effects on the health of human beings and animals. Today, the relationship between presence of asbestos fibers in the air breathed by humans and developing serious diseases such as lung cancer (asbestosis) and mesothelioma has been proven. The objectives of this study were to monitor the levels of asbestos fibers in ambient air of Mashhad, Iran during 2018, and to draw its Geographic Information System (GIS) distribution map for the city. In this descriptive study, 13 sampling points in Mashhad city were chosen. Sampling of asbestos was carried out for 3 hour during summer and winter at 2018. Sampling of asbestos was performed using MCE (Mixed Cellulose Ester) membrane filters (pour size 0.45 µm; diameter: 25 mm) and cassette holder and peripheral pump. The samples were the analyzed by the phase contrast microscopy (PCM) method (NIOSH7400). Also, to investigate the type of asbestos and for more accurate counting of fibers, Scanning Electron Microscopy (SEM) analysis was utilized. Meteorological parameter were recorded through portable devices. To draw the graphs, Excel, R and Arc GIS software were used. Results showed that the mean asbestos fiber concentrations were equal to 11.40 ± 2.14 and 14.38 ± 2.52 f/L in summer and winter, respectively. The maximum level of asbestos fiber was detected in the station of Baitolmoghaddas square by 26.64 ± 2.14 and 19.3 SEM f/L in winter and summer, respectively. High concentration of asbestos fiber observed in this study can be attributed to the heavy traffic, the presence of prominent industries in the vicinity of the study area, and topographic features. The results from this research recommends that suitable controlling policies should be regulated to reduce both ambient air asbestos and its adverse health endpoints in Mashhad.}, } @article {pmid33304846, year = {2020}, author = {Cheng, YY and Yuen, ML and Rath, EM and Johnson, B and Zhuang, L and Yu, TK and Aleksova, V and Linton, A and Kao, S and Clarke, CJ and McCaughan, BC and Takahashi, K and Lee, K}, title = {CDKN2A and MTAP Are Useful Biomarkers Detectable by Droplet Digital PCR in Malignant Pleural Mesothelioma: A Potential Alternative Method in Diagnosis Compared to Fluorescence In Situ Hybridisation.}, journal = {Frontiers in oncology}, volume = {10}, number = {}, pages = {579327}, pmid = {33304846}, issn = {2234-943X}, abstract = {BACKGROUND: The diagnosis of malignant pleural mesothelioma (MPM) can be difficult, in part due to the difficulty in distinguishing between MPM and reactive mesothelial hyperplasia (RMH). The tumor suppressor gene, CDKN2A, is frequently silenced by epigenetic mechanisms in many cancers; in the case of MPM it is mostly silenced via genomic deletion. Co-deletion of the CDKN2A and methylthioadenosine phosphorylase (MTAP) genes has been researched extensively and discovered to be a highly specific characteristic of MPM. Most studies have used FISH to detect the deletion of CDKN2A and IHC for MTAP as a surrogate for this. In this study, we aim to investigate and validate droplet digital PCR (ddPCR) as an emerging alternative and efficient testing method in diagnosing MPM, by particularly emphasizing on the loss of MTAP and CDKN2A.

METHODS: This study included 75 formalin fixed paraffin embedded (FFPE) MPM tissue, and 12 normal pleural tissue and 10 RMH as control. Additionally, primary MPM cell lines and normal pleural samples were used as biomarker detection controls, as established in our previous publication. All FFPE specimens were processed to isolate the DNA, that was subsequently used for ddPCR detection of CDKN2A and MTAP. FFPE samples were also analyzed by fluorescence in situ hybridization (FISH) for CDKN2A and MTAP deletion, and for MTAP IHC expression. Concordance of IHC and ddPCR with FISH were studied in these samples.

RESULTS: 95% and 82% of cases showed co-deletion of both MTAP and CDKN2A when determined by FISH and ddPCR respectively. ddPCR has a sensitivity of 72% and specificity of 100% in detecting CDKN2A homozygous loss in MPM. ddPCR also has a concordance rate of 92% with FISH in detecting homozygous loss of CDKN2A. MTAP IHC was 68% sensitive and 100% specific for detecting CDKN2A homozygous loss in MPM when these losses were determined by ddPCR.

CONCLUSION: Our study confirms that MTAP is often co-deleted with CDKN2A in MPM. Our in-house designed ddPCR assays for MTAP and CDKN2A are useful in differentiating MPM from RMH, and is highly concordant with FISH that is currently used in diagnosing MPM. ddPCR detection of these genetic losses can potentially be utilized as an alternative method in the diagnosis of MPM and for the future development of a less-invasive MPM-specific detection technique on MPM tumor tissue DNA.}, } @article {pmid33304592, year = {2021}, author = {Cheah, HM and Fitzgerald, D and Louw, A and Creaney, J and Lee, YCG}, title = {Hyaluronic acid in viscous malignant mesothelioma pleural effusion.}, journal = {Respirology case reports}, volume = {9}, number = {1}, pages = {e00694}, pmid = {33304592}, issn = {2051-3380}, abstract = {Malignant pleural effusion (MPE) is common with mesothelioma. We report two cases of extraordinarily viscous MPEs associated with mesothelioma. The viscosity prohibited spontaneous gravity-dependent drainage via indwelling pleural catheters. Our ex vivo experiments found very high hyaluronic acid (HA) content within the fluid. Treatment of the fluid with hyaluronidase, but not with deoxyribonucleases, significantly reduced fluid viscosity. The results provide proof that HA can contribute to high viscosity of pleural fluid in mesothelioma. Research into strategies of counteracting HA properties in the management of MPEs may provide further insight.}, } @article {pmid33300108, year = {2021}, author = {Dell'Anno, I and Martin, SA and Barbarino, M and Melani, A and Silvestri, R and Bottaro, M and Paolicchi, E and Corrado, A and Cipollini, M and Melaiu, O and Giordano, A and Luzzi, L and Gemignani, F and Landi, S}, title = {Drug-repositioning screening identified fludarabine and risedronic acid as potential therapeutic compounds for malignant pleural mesothelioma.}, journal = {Investigational new drugs}, volume = {39}, number = {3}, pages = {644-657}, pmid = {33300108}, issn = {1573-0646}, mesh = {Antineoplastic Agents/*pharmacology ; Cell Line ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Drug Repositioning ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Mesothelioma/*drug therapy/genetics/metabolism ; Pleural Neoplasms/*drug therapy/genetics/metabolism ; Risedronic Acid/*pharmacology ; STAT1 Transcription Factor/*antagonists & inhibitors/metabolism ; Vidarabine/*analogs & derivatives/pharmacology ; }, abstract = {Objectives Malignant pleural mesothelioma (MPM) is an occupational disease mainly due to asbestos exposure. Effective therapies for MPM are lacking, making this tumour type a fatal disease. Materials and Methods In order to meet this need and in view of a future "drug repositioning" approach, here we screened five MPM (Mero-14, Mero-25, IST-Mes2, NCI-H28 and MSTO-211H) and one SV40-immortalized mesothelial cell line (MeT-5A) as a non-malignant model, with a library of 1170 FDA-approved drugs. Results Among several potential compounds, we found that fludarabine (F-araA) and, to a lesser extent, risedronic acid (RIS) were cytotoxic in MPM cells, in comparison to the non-malignant Met-5A cells. In particular, F-araA reduced the proliferation and the colony formation ability of the MPM malignant cells, in comparison to the non-malignant control cells, as demonstrated by proliferation and colony formation assays, in addition to measurement of the phospho-ERK/total-ERK ratio. We have shown that the response to F-araA was not dependent upon the expression of DCK and NT5E enzymes, nor upon their functional polymorphisms (rs11544786 and rs2295890, respectively). Conclusion This drug repositioning screening approach has identified that F-araA could be therapeutically active against MPM cells, in addition to other tumour types, by inhibiting STAT1 expression and nucleic acids synthesis. Further experiments are required to fully investigate this.}, } @article {pmid33257382, year = {2020}, author = {Tanaka, T and Miyamoto, Y and Sakai, A and Fujimoto, N}, title = {Nivolumab for malignant peritoneal mesothelioma.}, journal = {BMJ case reports}, volume = {13}, number = {11}, pages = {}, pmid = {33257382}, issn = {1757-790X}, mesh = {Aged ; Antineoplastic Agents, Immunological/*therapeutic use ; Humans ; Immune Checkpoint Inhibitors/therapeutic use ; Male ; Mesothelioma, Malignant/diagnostic imaging/*drug therapy ; Nivolumab/*therapeutic use ; Peritoneal Neoplasms/diagnostic imaging/*drug therapy ; Radiography, Abdominal ; Tomography, X-Ray Computed ; }, abstract = {Malignant peritoneal mesothelioma (MPeM) is a highly malignant neoplasm of the peritoneum, which carries a poor prognosis. A 70-year-old man, who was employed in the shipbuilding industry and exposed to asbestos for 50 years, was found to have a low-density lesion in the peritoneum around the liver and spleen, associated with multiple mediastinal and parasternal lymphadenopathy. Laparoscopic exploration was performed, and biopsy specimen analysis led to a diagnosis of MPeM. Initial systemic chemotherapy comprising cisplatin and pemetrexed yielded a modest cytoreductive effect. However, 4 months later, the patient presented with abdominal distension and anorexia. CT images revealed massive ascites, bowel obstruction and an enlarged intra-abdominal tumour, which was considered progression of the MPeM. The patient was treated with nivolumab. Bowel obstruction was improved after the first administration, and his sense of abdomen distension completely disappeared after the third administration. This case supports the utility of immunotherapy in MPeM.}, } @article {pmid33238762, year = {2021}, author = {Arulananda, S and Lee, EF and Fairlie, WD and John, T}, title = {The role of BCL-2 family proteins and therapeutic potential of BH3-mimetics in malignant pleural mesothelioma.}, journal = {Expert review of anticancer therapy}, volume = {21}, number = {4}, pages = {413-424}, doi = {10.1080/14737140.2021.1856660}, pmid = {33238762}, issn = {1744-8328}, mesh = {Antineoplastic Agents/*pharmacology ; Apoptosis/drug effects ; Biomimetic Materials/pharmacology ; Cell Survival ; Humans ; Mesothelioma/*drug therapy/pathology ; Molecular Targeted Therapy ; Pleural Neoplasms/*drug therapy/pathology ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Survival Rate ; }, abstract = {Introduction: With limited recent therapeutic changes, malignant pleural mesothelioma (MPM) is associated with poor survival and death within 12 months, making it one of the most lethal malignancies. Due to unregulated asbestos use in developing countries and home renovation exposures, cases of MPM are likely to present for decades. As MPM is largely driven by dysregulation of tumor suppressor genes, researchers have examined other mechanisms of subverting tumor proliferation and spread. Over-expression of pro-survival BCL-2 family proteins impairs cells from undergoing apoptosis, and BH3-mimetics targeting them are a novel treatment option across various cancers, though have not been widely investigated in MPM.Areas covered: This review provides an overview of MPM and its current treatment landscape. It summarizes the role of BCL-2 family proteins in tumorigenesis and the therapeutic potential of BH3-mimetics . Finally, it discusses the role of BCL-2 proteins in MPM and the pre-clinical rationale for investigating BH3-mimetics as a therapeutic strategy.Expert opinion: As a disease without readily actionable oncogene driver mutations and with modest benefit from immune checkpoint inhibition, novel therapeutic options are urgently needed for MPM. Hence, BH3-mimetics provide a promising treatment option, with evidence supporting dependence on pro-survival BCL-2 proteins for MPM cell survival.}, } @article {pmid33233407, year = {2020}, author = {Cugliari, G and Catalano, C and Guarrera, S and Allione, A and Casalone, E and Russo, A and Grosso, F and Ferrante, D and Viberti, C and Aspesi, A and Sculco, M and Pirazzini, C and Libener, R and Mirabelli, D and Magnani, C and Dianzani, I and Matullo, G}, title = {DNA Methylation of FKBP5 as Predictor of Overall Survival in Malignant Pleural Mesothelioma.}, journal = {Cancers}, volume = {12}, number = {11}, pages = {}, pmid = {33233407}, issn = {2072-6694}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive tumor with median survival of 12 months and limited effective treatments. The scope of this study was to study the relationship between blood DNA methylation (DNAm) and overall survival (OS) aiming at a noninvasive prognostic test. We investigated a cohort of 159 incident asbestos exposed MPM cases enrolled in an Italian area with high incidence of mesothelioma. Considering 12 months as a cut-off for OS, epigenome-wide association study (EWAS) revealed statistically significant (p value = 7.7 × 10[-9]) OS-related differential methylation of a single-CpG (cg03546163), located in the 5'UTR region of the FKBP5 gene. This is an independent marker of prognosis in MPM patients with a better performance than traditional inflammation-based scores such as lymphocyte-to-monocyte ratio (LMR). Cases with DNAm < 0.45 at the cg03546163 had significantly poor survival compared with those showing DNAm ≥ 0.45 (mean: 243 versus 534 days; p value< 0.001). Epigenetic changes at the FKBP5 gene were robustly associated with OS in MPM cases. Our results showed that blood DNA methylation levels could be promising and dynamic prognostic biomarkers in MPM.}, } @article {pmid33230247, year = {2020}, author = {Jiang, Z and Shen, W and Ying, S and Gao, Z and He, X and Chen, R and Xia, H and Guo, X and Fang, Y and Zhang, Y and Miao, J and Zhou, J and Zhang, X and Chen, J and Lou, J}, title = {Overexpression of fibulin-3 in tumor tissue predicts poor survival of malignant mesothelioma patients from hand-spinning asbestos exposed area in eastern China.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {20373}, pmid = {33230247}, issn = {2045-2322}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Biomarkers, Tumor/*genetics/metabolism ; Extracellular Matrix Proteins/*genetics/metabolism ; Female ; *Gene Expression Regulation, Neoplastic ; HMGB1 Protein/*genetics/metabolism ; Humans ; Kaplan-Meier Estimate ; Lung Neoplasms/chemically induced/diagnosis/*genetics/mortality ; Male ; Mesothelioma, Malignant/chemically induced/diagnosis/*genetics/mortality ; Microarray Analysis ; Middle Aged ; Prognosis ; Proportional Hazards Models ; }, abstract = {Fibulin-3 is an extracellular matrix glycoprotein widely expressed in various tissues. Tissue fibulin-3 expression have never been reported in association with prognosis of mesothelioma. Hence, we sought to determine the association between fibulin-3 expression and mesothelioma survival. We made a tissue microarray, which was comprised of cancer and normal tissue from mesothelioma patients (n = 82) during the period 1998-2017 in China. Fibulin-3 and HGMB1 expression were analyzed by immunohistochemistry method. Kaplan-Meier method and Cox proportional hazard models were used for analyzing survival data. Overall, 61 cases (74.4%) were female; 90.2% were of epithelioid type; the median overall survival time was 12.5 months. Fibulin-3 and HMGB1 were highly expressed in tumor tissue rather than adjacent tissue. The expression of fibulin-3 in tissue was correlated with that of HMGB1 (r = 0.32, P = 0.003). High expression of fibulin-3 in tumor tissue could predict poor survival in patients with mesothelioma (P = 0.02). This remained true in a multivariate model, with a significant hazard ratio of 1.91. We demonstrated that fibulin-3 in tumor tissue was a novel biomarker of poor survival of mesothelioma, suggesting it may be a relevant target for therapeutic intervention.}, } @article {pmid33197421, year = {2021}, author = {Xia, H and Feng, L and Lin, L and Jiang, Z and Chen, J and Shi, W and Ying, S and Yu, M and Ju, L and Zhu, L and Shi, L and Zhang, X and Lou, J}, title = {Exploration of identifying novel serum biomarkers for malignant mesothelioma using iTRAQ combined with 2D-LC-MS/MS.}, journal = {Environmental research}, volume = {193}, number = {}, pages = {110467}, doi = {10.1016/j.envres.2020.110467}, pmid = {33197421}, issn = {1096-0953}, mesh = {Biomarkers ; Biomarkers, Tumor ; Chromatography, Liquid ; Humans ; *Mesothelioma/diagnosis ; *Mesothelioma, Malignant ; *Pleural Neoplasms ; ROC Curve ; Tandem Mass Spectrometry ; }, abstract = {Malignant mesothelioma (MM) is an aggressive cancer linked to asbestos exposure. Its poor prognosis makes early diagnosis extremely important, which would provide an opportunity for early treatment and potentially changing outcomes. This study aimed to explore the underlying mechanisms of MM and discover novel noninvasive biomarkers for the diagnosis of malignant mesothelioma. Using Isobaric tags for relative and absolute quantitation (iTRAQ) combined with two-dimensional liquid chromatography/tandem mass spectrometry (2D LC-MS/MS), a total of 145 differentially expressed serum proteins were identified between MM patients and healthy controls. The identified proteins were further analyzed by bioinformatics, out of which three candidate biomarkers (Filamin A (FLNA), Fibulin 1 (FBLN1) and Thrombospondin-1 (TSP-1)) were validated in large cohorts of patients with asbestos-related diseases including MM patients by ELISA assay. Receiver operating characteristic (ROC) curve analysis showed that serum FLNA, FBLN1 and TSP-1 had high diagnostic values in distinguishing MM patients from healthy controls, individuals with asbestos exposure (AE), and patients with pleural plaques (PP) or asbestosis. Meanwhile, serum FBLN1 and TSP-1 possessed good diagnostic values in distinguishing asbestosis patients from healthy controls and individuals with AE. The combination of FLNA, FBLN1, and TSP-1 proteins had higher sensitivity and specificity in discriminating patients with MM, PP and asbestosis. Our findings indicated that analysis of serum proteome using iTRAQ is a feasible strategy for biomarker discovery, and serum FLNA, FBLN1 and TSP-1 may be promising candidates for diagnosis of malignant mesothelioma and screening of at-risk individuals.}, } @article {pmid33149905, year = {2020}, author = {Filetti, V and Vitale, E and Broggi, G and Hagnäs, MP and Candido, S and Spina, A and Lombardo, C}, title = {Update of in vitro, in vivo and ex vivo fluoro-edenite effects on malignant mesothelioma: A systematic review (Review).}, journal = {Biomedical reports}, volume = {13}, number = {6}, pages = {60}, pmid = {33149905}, issn = {2049-9434}, abstract = {Fluoro-edenite (FE), asbestiform fiber found in Biancavilla (Sicily, Italy), presents various characteristics similar to the asbestos group, in particular two fibrous phases tremolite and actinolite. Indeed, epidemiological studies have shown that FE fibers have similar effects to those of asbestos fibers. Such studies have reported a high incidence of malignant mesothelioma (MM), an aggressive neoplasm of the serosal membranes lining the pleural cavity, in individuals residing there due to FE exposure in Biancavilla related to environmental contamination. Evidence has led to the classification of FE as a Group 1 human carcinogen by the International Agency for Research on Cancer (IARC). The aim of this systematic review is to compare the results achieved in in vitro, in vivo and ex vivo experimental studies involving FE in order to update the current knowledge on the pathogenesis and molecular mechanisms responsible for FE-mediated MM development as well as the availability of effective biomarkers for MM prevention and diagnosis. This review is focused on the pathophysiological mechanisms mediated by inflammation induced by FE fiber exposure and which are responsible for MM development. This review also discusses the discovery of new diagnostic and prognostic biomarkers for the management of this pathology. It is known that the risk of cancer development increases with chronic inflammation, arising from enhanced reactive oxygen species (ROS) and NO[•] production stimulated by the body to remove exogenous agents, causing DNA damage and enhanced signal transduction that may lead to activation of oncogenes. Studies concerning MM biomarker discovery indicate that several biomarkers have been proposed for MM, but mesothelin is the only Food and Drug Administration (FDA)-approved biomarker for MM, with limitations. In recent studies, in silico analysis to identify selected miRNAs highly deregulated in cancer samples when compared with normal control have been developed. This in silico approach could represent an effort in the field of biomarker discovery for MM.}, } @article {pmid33149886, year = {2020}, author = {Notue, YA and Mbessoh, UI and Nganwa, G and Pambe, JN and Mefire, AC and Moifo, B and Sando, Z}, title = {Sarcomatoid malignant peritoneal mesothelioma presenting as a localized mesenteric tumor with no previous asbestos exposure.}, journal = {Journal of surgical case reports}, volume = {2020}, number = {10}, pages = {rjaa419}, pmid = {33149886}, issn = {2042-8812}, abstract = {Sarcomatoid malignant peritoneal mesothelioma is the rarest and most lethal form of peritoneal mesothelioma. We present the case of a sarcomatoid malignant peritoneal mesothelioma presenting as a localized mesenteric tumor in a 54-year-old female with no previous asbestos exposure. This clinical presentation is extremely rare and is the first documented in Cameroon.}, } @article {pmid33148505, year = {2020}, author = {Khaliullin, TO and Kisin, ER and Guppi, S and Yanamala, N and Zhernovkov, V and Shvedova, AA}, title = {Differential responses of murine alveolar macrophages to elongate mineral particles of asbestiform and non-asbestiform varieties: Cytotoxicity, cytokine secretion and transcriptional changes.}, journal = {Toxicology and applied pharmacology}, volume = {409}, number = {}, pages = {115302}, doi = {10.1016/j.taap.2020.115302}, pmid = {33148505}, issn = {1096-0333}, mesh = {Air Pollutants, Occupational/adverse effects ; Animals ; Asbestos/*adverse effects ; Asbestos, Amphibole/adverse effects ; Autoimmune Diseases/chemically induced/metabolism ; Bodily Secretions/*drug effects ; Cells, Cultured ; Cytokines/*metabolism ; Lung Neoplasms/chemically induced/metabolism ; Macrophages, Alveolar/*drug effects/metabolism ; Mesothelioma, Malignant/chemically induced/metabolism ; Mice ; Mice, Inbred C57BL ; Mineral Fibers/adverse effects ; Minerals/*adverse effects ; Occupational Exposure/adverse effects ; Particle Size ; Particulate Matter/adverse effects ; Transcription, Genetic/*drug effects ; }, abstract = {Human exposures to asbestiform elongate mineral particles (EMP) may lead to diffuse fibrosis, lung cancer, malignant mesothelioma and autoimmune diseases. Cleavage fragments (CF) are chemically identical to asbestiform varieties (or habits) of the parent mineral, but no consensus exists on whether to treat them as asbestos from toxicological and regulatory standpoints. Alveolar macrophages (AM) are the first responders to inhaled particulates, participating in clearance and activating other resident and recruited immunocompetent cells, impacting the long-term outcomes. In this study we address how EMP of asbestiform versus non-asbestiform habit affect AM responses. Max Planck Institute (MPI) cells, a non-transformed mouse line that has an AM phenotype and genotype, were treated with mass-, surface area- (s.a.), and particle number- (p.n.) equivalent concentrations of respirable asbestiform and non-asbestiform riebeckite/tremolite EMP for 24 h. Cytotoxicity, cytokines secretion and transcriptional changes were evaluated. At the equal mass, asbestiform EMP were more cytotoxic, however EMP of both habits induced similar LDH leakage and decrease in viability at s.a. and p.n. equivalent doses. DNA damage assessment and cell cycle analysis revealed differences in the modes of cell death between asbestos and respective CF. There was an increase in chemokines, but not pro-inflammatory cytokines after all EMP treatments. Principal component analysis of the cytokine secretion showed close clustering for the s.a. and p.n. equivalent treatments. There were mineral- and habit-specific patterns of gene expression dysregulation at s.a. equivalent doses. Our study reveals the critical nature of EMP morphometric parameters for exposure assessment and dosing approaches used in toxicity studies.}, } @article {pmid33143837, year = {2020}, author = {Liu, Y and Tong, J and Ling, X and Cao, W and Fang, L}, title = {A Case of Systemic Lupus Erythematosus with Malignant Pleural Mesothelioma in a 42-year Woman.}, journal = {Journal of the College of Physicians and Surgeons--Pakistan : JCPSP}, volume = {30}, number = {10}, pages = {1099-1101}, doi = {10.29271/jcpsp.2020.10.1099}, pmid = {33143837}, issn = {1681-7168}, mesh = {Female ; Humans ; *Lupus Erythematosus, Systemic/complications/diagnosis/drug therapy ; *Mesothelioma/diagnosis/drug therapy ; *Mesothelioma, Malignant ; *Pleural Effusion/etiology ; *Pleural Neoplasms/diagnosis/drug therapy ; }, abstract = {Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease characterised by inflammation. Malignant pleural mesothelioma (MPM) is a highly invasive malignant tumor derived from pleural mesothelial cells. Here, we report a case of SLE with MPM. A 42-year woman with no exposure to asbestos presented with severe left chest pain. Initially, we diagnosed her with SLE because of the clinical manifestations and high antinuclear antibody titer. Finally, a diagnosis of MPM was made, based on pleural biopsy. Her condition was under control after one cycle of chemotherapy and oral methotrexate. However, three years later, she was admitted with dyspnea, mild orthopnea, and tachycardia, and died one month later after discontinuing treatment. MPM is rare, and MPM with SLE is even rarer. We should pay attention to pleural effusion when diagnosing SLE. If possible, a pleural biopsy should be performed to reduce misdiagnosis and missed diagnosis. Key Words: Pleural effusion, Systemic lupus erythematosus (SLE), Mesothelioma.}, } @article {pmid33133607, year = {2020}, author = {MacMillan, M and Roy, B and McLaren, S and Nowak, AK and Thomas, R and Lee, YCG}, title = {Widespread pulmonary invasion by malignant pleural mesothelioma: an important diagnostic consideration.}, journal = {Respirology case reports}, volume = {8}, number = {9}, pages = {e00675}, pmid = {33133607}, issn = {2051-3380}, abstract = {We report a rare case of early and extensive pulmonary invasion of malignant pleural mesothelioma (MPM) in a 70-year-old woman. She first presented with a hydropneumothorax and subsequent workup, including video-assisted thoracoscopy (VAT), confirmed MPM. After VAT, she developed dyspnoea, cough, and widespread pulmonary infiltrates of uncertain aetiology. These infiltrates progressed over the following months, failed to respond to antibiotics, and were strongly fluorodeoxyglucose (FDG)-avid on positron emission tomography (PET). Bronchoalveolar lavage (BAL) yielded extremely viscous fluid containing mesothelioma cells. These cells were also found in the sputum when nebulized deoxyribonuclease (DNase) was trialled to enhance clearance of the pulmonary fluid. The patient deteriorated rapidly with progressive mediastinal and contralateral MPM involvement and died one month later. This case highlights the importance of including tumour invasion as a differential diagnosis of non-resolving pulmonary infiltrates in patients with MPM.}, } @article {pmid33133014, year = {2020}, author = {Gesmundo, I and Silvagno, F and Banfi, D and Monica, V and Fanciulli, A and Gamba, G and Congiusta, N and Libener, R and Riganti, C and Ghigo, E and Granata, R}, title = {Calcitriol Inhibits Viability and Proliferation in Human Malignant Pleural Mesothelioma Cells.}, journal = {Frontiers in endocrinology}, volume = {11}, number = {}, pages = {559586}, pmid = {33133014}, issn = {1664-2392}, mesh = {Calcitriol/*pharmacology/therapeutic use ; Cell Cycle Checkpoints/drug effects/physiology ; Cell Line, Tumor ; Cell Proliferation/*drug effects/physiology ; Cell Survival/*drug effects/physiology ; Humans ; Mesothelioma, Malignant/drug therapy/*pathology ; Tumor Cells, Cultured ; Vitamins/*pharmacology/therapeutic use ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor, often associated with exposure to asbestos and characterized by poor prognosis and limited treatment options. The biologically active form of vitamin D, calcitriol, exerts anticancer effects in many cell types, both alone and in combination with chemotherapy drugs, through binding to vitamin D receptor (VDR); however, the role of calcitriol in MPM is still unknown. This study aimed to determine the potential antitumor role of calcitriol in MPM. The results showed that calcitriol reduces cell viability and proliferation in human MPM cells lines, which express both cytoplasmic and nuclear VDR; furthermore, calcitriol potentiated the inhibitory activity of the chemotherapy drug PEM. These effects were paralleled by cell cycle arrest and inhibition in expression of c-Myc and cyclins involved in cell cycle progression. Exposure of MPM cells to calcitriol also produced an alteration in mitochondrial function and inhibition in the expression of respiratory chain complex subunits. Finally, the inhibitory effects of calcitriol were also observed on viability of human primary MPM cells. Collectively, these results indicate a novel anticancer role for calcitriol in MPM, suggesting potential for vitamin D derivatives, alone or in combination with chemotherapy, in the treatment of this malignancy.}, } @article {pmid33119974, year = {2020}, author = {Barbieri, PG and Mirabelli, D and Madeo, E and Somigliana, A}, title = {[Asbestos exposure and related diseases among friction products workers (1971-2016)].}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {42}, number = {3}, pages = {145-152}, pmid = {33119974}, issn = {1592-7830}, mesh = {Aged ; Air Pollutants, Occupational/analysis ; Asbestos, Amphibole/analysis ; Asbestos, Serpentine/analysis/*toxicity ; Asbestosis/*epidemiology ; Automobiles ; Female ; Friction ; Humans ; Italy ; *Lung ; Lung Neoplasms/*epidemiology/etiology ; Male ; *Manufacturing Industry ; Mesothelioma/epidemiology ; Middle Aged ; Mineral Fibers/analysis ; Occupational Exposure/*adverse effects/analysis/statistics & numerical data ; Preliminary Data ; Talc/toxicity ; Time Factors ; }, abstract = {Worldwide studies have been published on the mortality of workers employed in asbestos-based materials for the production of clutches and brakes. However no one of these studies is related to Italian cases. Furthermore, not even surveys have been conducted in Italy to characterize the correlation between asbestos exposures and the possible occurring of asbestos-related disease. Our objectives are the following: i) to assess and quantify the asbestos exposure cases, ii) to describe the nature and the frequency of asbestos-related diseases among blue collar employees of an important factory producing brakes and clutches with chrysotile asbestos content from 1971 to 1993 and iii) to provide preliminary data on cumulative asbestos exposure estimated using lung fibre burden analysis. Critical appraisal of airborne asbestos fibre measurements and identification of cases of asbestos-related diseases between the blue collar employees, either notified to the local health authority or recovered from the Italian national Mesothelioma registry was investigated. Lung fibre burden analysis using the lung tissue samples from two deceased blue collar employees was also performed. Airborne asbestos fibre measurements (carried out in 1982) suggested asbestos fibres average concentrations of about 0.3 f/ml, while all 1992 measurements showed results below 0.1 f/ml. Furthermore, since 1988, we identified four cases of pleural plaques, three cases of asbestosis and seven cases of lung cancer. No case of malignant mesothelioma was found. In both lung cancer cases, analysed to measure the lung fibre burden, commercial amphiboles were absent or in limited concentration but chrysotile and, especially, tremolite asbestos were present in noticeable amount. In conclusion, since 1971 and up to early 1980s, exposure to chrysotile asbestos and talc, likely contaminated by tremolite, had been significant and comparable to levels causing asbestosis long-term risk. No case of malignant mesothelioma was found, that is consistent with the absence of amphiboles and with the lower risk of mesothelioma associated with the chrysotile asbestos. However a subset of the blue collar employees, the ones employed later on, could still have not reached the full risk condition, and so being still at risk of developing malignant mesothelioma. In the two lung cancer cases studied, the lung fibre burden was essentially made of chrysotile and tremolite. Lastly, lung cancer occurrence in the population of blue collar employees has been likely underestimated and the correct determination of lung cancer risk should be done through the mortality analysis of this population.}, } @article {pmid33093002, year = {2020}, author = {Brandi, G and Deserti, M and Palloni, A and Turchetti, D and Zuntini, R and Pedica, F and Frega, G and De Lorenzo, S and Abbati, F and Rizzo, A and Di Marco, M and Massari, F and Tavolari, S}, title = {Intrahepatic cholangiocarcinoma development in a patient with a novel BAP1 germline mutation and low exposure to asbestos.}, journal = {Cancer genetics}, volume = {248-249}, number = {}, pages = {57-62}, doi = {10.1016/j.cancergen.2020.10.001}, pmid = {33093002}, issn = {2210-7762}, mesh = {Asbestos/*adverse effects ; Bile Duct Neoplasms/etiology/*pathology ; *Carcinogens ; Cholangiocarcinoma/etiology/*pathology ; Female ; *Genetic Predisposition to Disease ; *Germ-Line Mutation ; Humans ; Middle Aged ; Prognosis ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {BRCA1 associated protein-1 (BAP1) germline mutations define a novel hereditary cancer syndrome, namely BAP1 tumor predisposition syndrome (BAP1-TPDS), characterized by an increased susceptibility to develop different cancer types, including mesothelioma, uveal and cutaneous melanoma, renal cell carcinoma, and basal cell and squamous cell carcinoma. Currently, the role of BAP1 germline mutations in intrahepatic cholangiocarcinoma (iCCA) pathogenesis is less known. Here we report the first clinical case of a female patient who developed an iCCA when she was 47-years-old and was found to carry a novel germline mutation at a splicing site of exon 4 in BAP1 gene (NM_004656.4: c.255_255+6del). An accurate anamnesis revealed the absence of risk factors linked to iCCA development, except for a low occupational exposure to asbestos. In tumor tissue, BAP1 sequencing, multiplex ligation-dependent probe amplification and immunoistochemistry showed the loss of heterozygosity and lack of nuclear expression, suggesting that BAP1 wild-type allele and functional protein were lost in cancer cells, in line with the classical two-hit model of tumor suppressor genes. Further studies are needed to confirm whether iCCA may be included into BAP1-TPDS cancer phenotypes and whether minimal asbestos exposure may facilitate the development of this malignancy in individuals carrying BAP1 germline mutations.}, } @article {pmid33087407, year = {2020}, author = {Wong, JYY and Rice, C and Blair, A and Silverman, DT}, title = {Mesothelioma risk among those exposed to chrysotile asbestos only and mixtures that include amphibole: a case-control study in the USA, 1975-1980.}, journal = {Occupational and environmental medicine}, volume = {}, number = {}, pages = {}, pmid = {33087407}, issn = {1470-7926}, support = {Z01 CP010136/ImNIH/Intramural NIH HHS/United States ; ZIA CP010120/ImNIH/Intramural NIH HHS/United States ; }, abstract = {OBJECTIVES: Occupational asbestos exposure is causally linked to mesothelioma. However, whether exposure to only chrysotile asbestos is associated with mesothelioma risk, and the heterogeneity in risk by different fibre types/lengths remains unclear. We investigated whether mesothelioma risk differs among workers exposed to only chrysotile asbestos compared with chrysotile and ≥1 amphibole (ie, amosite, tremolite, anthophyllite and crocidolite) over the working lifetime.

METHODS: We analysed next-of-kin interview data including occupational histories for 580 white men (176 cases and 404 controls) from a case-control study of mesothelioma conducted in the USA in 1975-1980. Asbestos exposure was determined by an occupational hygienist using a job-exposure matrix and exposure categories included chrysotile only and nine chrysotile-amphibole mixtures. Logistic regression models were used to estimate the ORs and 95% CIs of mesothelioma, comparing each asbestos category to the unexposed group, adjusted for age at death and data source. Analysis of contrasts was used to assess overall heterogeneity and pair-wise differences in risk.

RESULTS: Exposure to long and short chrysotile only was associated with increased mesothelioma risk compared with the unexposed (OR=3.8 (95% CI 1.3 to 11.2)). The complex mixture of extra-long amosite, short and long chrysotile, tremolite and anthophyllite was associated with the highest risk (OR=12.8 (95% CI 4.1 to 40.2)). There was evidence for overall heterogeneity among the asbestos exposure categories (p heterogeneity=0.02). However, the lower risk observed for exposure to chrysotile only compared with the complex mixture was not significant (p difference=0.10).

CONCLUSIONS: Our findings suggest that policies aimed at regulating asbestos should target both pure chrysotile and mixtures that include amphibole.}, } @article {pmid33085641, year = {2020}, author = {Piber, P and Vavpetic, N and Goricar, K and Dolzan, V and Kovac, V and Franko, A}, title = {The influence of genetic variability in IL1B and MIR146A on the risk of pleural plaques and malignant mesothelioma.}, journal = {Radiology and oncology}, volume = {54}, number = {4}, pages = {429-436}, pmid = {33085641}, issn = {1581-3207}, mesh = {Aged ; Alleles ; Case-Control Studies ; Female ; Genetic Variation ; Genotype ; Humans ; Inflammation Mediators/metabolism ; Interleukin-1beta/*genetics ; Male ; Mesothelioma, Malignant/diagnostic imaging/*genetics ; MicroRNAs/*genetics ; Middle Aged ; Pleural Diseases/diagnostic imaging/*genetics ; Pleural Neoplasms/diagnostic imaging/*genetics ; Polymorphism, Single Nucleotide ; Risk Factors ; }, abstract = {Background Asbestos exposure is associated with the development of pleural plaques as well as malignant mesothelioma (MM). Asbestos fibres activate macrophages, leading to the release of inflammatory mediators including interleukin 1 beta (IL-1β). The expression of IL-1β may be influenced by genetic variability of IL1B gene or regulatory microRNAs (miRNAs). This study investigated the effect of polymorphisms in IL1B and MIR146A genes on the risk of developing pleural plaques and MM. Subjects and methods In total, 394 patients with pleural plaques, 277 patients with MM, and 175 healthy control subjects were genotyped for IL1B and MIR146A polymorphisms. Logistic regression was used in statistical analysis. Results We found no association between MIR146A and IL1B genotypes, and the risk of pleural plaques. MIR146A rs2910164 was significantly associated with a decreased risk of MM (OR = 0.31, 95% CI = 0.13-0.73, p = 0.008). Carriers of two polymorphic alleles had a lower risk of developing MM, even after adjustment for gender and age (OR = 0.34, 95% CI = 0.14-0.85, p = 0.020). Among patients with known asbestos exposure, carriers of at least one polymorphic IL1B rs1143623 allele also had a lower risk of MM in multivariable analysis (OR = 0.50, 95% CI = 0.28-0.92, p = 0.025). The interaction between IL1B rs1143623 and IL1B rs1071676 was significantly associated with an increased risk of MM (p = 0.050). Conclusions Our findings suggest that genetic variability of inflammatory mediator IL-1β could contribute to the risk of developing MM, but not pleural plaques.}, } @article {pmid33069179, year = {2020}, author = {Janošíková, M and Nakládalová, M and Štěpánek, L and Boriková, A and Vildová, H and Fošum, M}, title = {Occurrence of asbestos-related occupational diseases in the Czech Republic in the last 20 years.}, journal = {Central European journal of public health}, volume = {28 Suppl}, number = {}, pages = {S37-S42}, doi = {10.21101/cejph.a6297}, pmid = {33069179}, issn = {1210-7778}, mesh = {*Asbestos/toxicity ; Czech Republic/epidemiology ; Humans ; *Mesothelioma/chemically induced/epidemiology ; *Occupational Diseases/epidemiology ; Retrospective Studies ; }, abstract = {OBJECTIVES: Asbestos-related diseases are still a current problem worldwide. What is their occurrence in the Czech Republic? The answer is the subject of this study, which aims to provide a general and regional overview of the situation over the last 20 years with a more detailed focus on mesothelioma, the development of which is highly associated with asbestos exposure and the issue of their recognition as an occupational disease.

METHODS: In its retrospective reviews, the study is based on analyses of data from the Institute of Health Information and Statistics of the Czech Republic and data from the Czech National Cancer Registry, which also interconnects.

RESULTS: In the last 20 years, 512 new cases of occupational diseases from asbestos have been reported, namely 228 cases of pleural thickening, 133 mesotheliomas, 92 asbestoses, and 59 cases of lung cancer. In the last 5 years, mesotheliomas (n = 39) predominated among the reported diseases with a 45% proportion in the total number of 86 cases. The trend in their incidence, as the only one among asbestos-related diseases, is not declining. There was a significant difference in the overall incidence of mesothelioma in a general population and the incidence of occupational mesotheliomas. At the national level, occupational aetiology was acknowledged in only 11.3% of cases of mesothelioma on average. The highest proportion of occupational mesotheliomas and the highest incidence of all asbestos-related diseases were found in regions where the largest asbestos processing plants were located.

CONCLUSION: The authors emphasize the importance of work history for the diagnostic process of asbestos-related diseases and also the need to perform follow-up examinations for their early detection.}, } @article {pmid33065463, year = {2020}, author = {Fusco, N and Vaira, V and Righi, I and Sajjadi, E and Venetis, K and Lopez, G and Cattaneo, M and Castellani, M and Rosso, L and Nosotti, M and Clerici, M and Ferrero, S}, title = {Characterization of the immune microenvironment in malignant pleural mesothelioma reveals prognostic subgroups of patients.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {150}, number = {}, pages = {53-61}, doi = {10.1016/j.lungcan.2020.09.026}, pmid = {33065463}, issn = {1872-8332}, mesh = {B7-H1 Antigen ; Humans ; *Lung Neoplasms ; Lymphocytes, Tumor-Infiltrating ; *Mesothelioma, Malignant ; Prognosis ; Tumor Microenvironment ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare tumor with an extremely poor prognosis. Its pathogenesis is related to an immune response against asbestos fibers. The T-lymphocytes, including CD8[POS] and CD4[POS] cells, are an important part of the MPM immune microenvironment, and likely contribute to the therapy resistance observed in these tumors. Here, we sought to characterize the MPM-specific lymphocytes subpopulations within the tumor immune microenvironment to identify novel clinically relevant immunologic subtypes of tumors. Representative formalin-fixed, paraffin-embedded (FFPE) tissue blocks of 88 MPMs were included in tissue microarrays and subjected to tumor-infiltrating lymphocytes (TILs) quantification and subtyping by immunohistochemistry (IHC) with antibodies specific for CD4, CD8, and CD19. Further, PD-L1 (clone 22C3) expression was assessed by IHC as a combined positive score (CPS). Our data show that PD-L1 expression by tumor cells or the presence of a sarcomatoid component is related to increased stromal TILs presence in MPM. Survival analyses showed that low CD4[POS] and high CD8[POS] stromal TILs are associated with poor patients' survival. In MPMs with PD-L1 CPS > 1, stromal CD8[HIGH] was a poor prognostic factor, akin stromal CD4[POS] peritumoral TILs correlated with a worse prognosis. Furthermore, we demonstrated that a high CD4[POS]/CD8[POS] ratio in the tumor immune microenvironment is an independent prognostic factor for survival. Finally, we provided evidence that the characterization of the stromal immune landscape of MPM predicts responses to chemotherapy in subgroups of MPM. The results of this study provide novel insights into the clinical scenario of immune-related biomarkers in MPM.}, } @article {pmid33055488, year = {2021}, author = {Sekine, I and Yamamoto, Y and Suzuki, T and Suzuki, H}, title = {Malignant Pleural Mesothelioma in Patients Who Previously Received Radiotherapy for Their First Malignant Tumor.}, journal = {Internal medicine (Tokyo, Japan)}, volume = {60}, number = {5}, pages = {663-665}, pmid = {33055488}, issn = {1349-7235}, mesh = {*Asbestos ; Humans ; *Lung Neoplasms/radiotherapy ; *Mesothelioma/radiotherapy ; *Mesothelioma, Malignant ; *Pleural Neoplasms/radiotherapy ; }, } @article {pmid33055477, year = {2021}, author = {Nakashima, K and Demura, Y and Oi, M and Tabata, M and Tada, T and Shiozaki, K and Akai, M and Ishizuka, T}, title = {The Association between Malignant Pleural Mesothelioma and Thoracic Radiation Therapy for Hodgkin's Lymphoma: The First Case Report in Japan.}, journal = {Internal medicine (Tokyo, Japan)}, volume = {60}, number = {5}, pages = {771-775}, pmid = {33055477}, issn = {1349-7235}, mesh = {*Asbestos ; Europe ; Female ; *Hodgkin Disease/radiotherapy ; Humans ; Japan/epidemiology ; *Mesothelioma/diagnosis/etiology ; *Mesothelioma, Malignant ; Middle Aged ; *Pleural Neoplasms/etiology/radiotherapy ; }, abstract = {Malignant pleural mesothelioma (MPM) is mostly observed in patients with a history of asbestos exposure. Although other causes are rare, there are several reports of MPM induced by therapeutic radiation, mainly in Europe and North America. However, no such case has been reported in Japan. We herein report a 50-year-old Japanese woman who developed MPM 25 years after thoracic radiation therapy for Hodgkin's lymphoma. The patient had no history of exposure to asbestos; therefore, her history of radiation therapy was considered to be the cause of MPM. Clinicians should consider secondary MPM in patients with a history of thoracic radiation therapy.}, } @article {pmid33054855, year = {2020}, author = {Saleh, DM and Alexander, WT and Numano, T and Ahmed, OHM and Gunasekaran, S and Alexander, DB and Abdelgied, M and El-Gazzar, AM and Takase, H and Xu, J and Naiki-Ito, A and Takahashi, S and Hirose, A and Ohnishi, M and Kanno, J and Tsuda, H}, title = {Comparative carcinogenicity study of a thick, straight-type and a thin, tangled-type multi-walled carbon nanotube administered by intra-tracheal instillation in the rat.}, journal = {Particle and fibre toxicology}, volume = {17}, number = {1}, pages = {48}, pmid = {33054855}, issn = {1743-8977}, mesh = {Air Pollutants/*toxicity ; Animals ; Asbestos, Crocidolite ; Carcinogenicity Tests ; Inhalation Exposure ; Lung ; Lung Neoplasms ; Mesothelioma ; Nanotubes, Carbon/*toxicity ; Rats ; Trachea/drug effects ; }, abstract = {BACKGROUND: Multi-walled carbon nanotubes can be divided into two general subtypes: tangled and straight. MWCNT-N (60 nm in diameter) and MWCNT-7 (80-90 nm in diameter) are straight-type MWCNTs, and similarly to asbestos, both are carcinogenic to the lung and pleura when administered to rats via the airway. Injection of straight-type MWCNTs into the peritoneal cavity also induces the development of mesothelioma, however, injection of tangled-type MWCNTs into the peritoneal cavity does not induce carcinogenesis. To investigate these effects in the lung we conducted a 2-year comparative study of the potential carcinogenicities of a straight-type MWCNT, MWCNT-A (approximately 150 nm in diameter), and a tangled-type MWCNT, MWCNT-B (7.4 nm in diameter) after administration into the rat lung. Crocidolite asbestos was used as the reference material, and rats administered vehicle were used as the controls. Test materials were administered by intra-Tracheal Intra-Pulmonary Spraying (TIPS) once a week over a 7 week period (8 administrations from day 1 to day 50), followed by a 2-year observation period without further treatment. Rats were administered total doses of 0.5 or 1.0 mg MWCNT-A and MWCNT-B or 1.0 mg asbestos.

RESULTS: There was no difference in survival between any of the groups. The rats administered MWCNT-A or asbestos did not have a significant increase in bronchiolo-alveolar hyperplasia or tumors in the lung. However, the rats administered MWCNT-B did have significantly elevated incidences of bronchiolo-alveolar hyperplasia and tumors in the lung: the incidence of bronchiolo-alveolar hyperplasia was 0/20, 6/20, and 9/20 in the vehicle, 0.5 mg MWCNT-B, and 1.0 mg MWCNT-B groups, respectively, and the incidence of adenoma and adenocarcinoma combined was 1/19, 5/20, and 7/20 in the vehicle, 0.5 mg MWCNT-B, and 1.0 mg MWCNT-B groups, respectively. Malignant pleural mesothelioma was not induced in any of the groups.

CONCLUSIONS: The results of this initial study indicate that tangled-type MWCNT-B is carcinogenic to the rat lung when administered via the airway, and that straight-type MWCNT-A did not have higher carcinogenic potential in the rat lung than tangled-type MWCNT-B.}, } @article {pmid33050791, year = {2020}, author = {Hariharan, A and Sun, S and Wipplinger, M and Felley-Bosco, E}, title = {RNA editing in mesothelioma: a look forward.}, journal = {Open biology}, volume = {10}, number = {10}, pages = {200112}, pmid = {33050791}, issn = {2046-2441}, mesh = {Adenosine Deaminase/metabolism ; Animals ; Cell Proliferation ; Disease Progression ; *Gene Expression Regulation, Neoplastic ; Genomic Instability ; Humans ; Interferon Type I/metabolism ; Mesothelioma/*genetics/metabolism/pathology/therapy ; Protein Binding ; *RNA Editing ; RNA Processing, Post-Transcriptional ; RNA-Binding Proteins/metabolism ; }, abstract = {RNA editing is a post-transcriptional process increasing transcript diversity, thereby regulating different biological processes. We recently observed that mutations resulting from RNA editing due to hydrolytic deamination of adenosine increase during the development of mesothelioma, a rare cancer linked to chronic exposure to asbestos. This review gathers information from the published literature and public data mining to explore several aspects of RNA editing and their possible implications for cancer growth and therapy. We address possible links between RNA editing and particular types of mesothelioma genetic and epigenetic alterations and discuss the relevance of an edited substrate in the context of current chemotherapy or immunotherapy.}, } @article {pmid33049597, year = {2020}, author = {Orbach, D and André, N and Brecht, IB and López Almaraz, R and Ben-Ami, T and Vermersch, S and Carton, M and Virgone, C and Bisogno, G and Schneider, DT and Bajciova, V and Reguerre, Y and Galateau-Salle, F and Stachowicz-Stencel, T and Dvir, R and Rees, H and Bien, E and Ferrari, A and Ben Arush, M}, title = {Mesothelioma in children and adolescents: the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) contribution.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {140}, number = {}, pages = {63-70}, doi = {10.1016/j.ejca.2020.09.011}, pmid = {33049597}, issn = {1879-0852}, mesh = {Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Chemotherapy, Adjuvant/methods ; Child ; Child, Preschool ; Cisplatin/therapeutic use ; Cytoreduction Surgical Procedures/methods ; Europe ; Female ; Follow-Up Studies ; Humans ; Infant ; Male ; Mesothelioma, Malignant/*drug therapy ; Neoadjuvant Therapy/methods ; Peritoneal Neoplasms/drug therapy ; Retrospective Studies ; Young Adult ; }, abstract = {INTRODUCTION: Very little is known about the characteristics of mesothelial tumours in the paediatric population. In adults with malignant mesothelioma, the pemetrexed-based regimen with cytoreductive surgery (CRS) is a standard of care in limited tumours, but long-term survival is uncommon.

MATERIAL AND METHODS: The European Cooperative Study Group on Pediatric Rare Tumors (EXPeRT) retrospectively reviewed children, adolescents and young adults (≤21 year) diagnosed with mesothelial tumours treated between 1987 and 2018.

RESULTS: Thirty-three patients were identified, 15 male and 18 female patients. One patient's exposure to asbestos was documented. Primary tumour was mainly in the peritoneum (23 patients). Histology was multicystic mesothelioma of the peritoneum (MCM) (six patients) or malignant mesothelioma (MM) (27 patients). Among MM, the first-line treatment comprised preoperative chemotherapy (14 cases), surgery only (three cases), chemotherapy only (five cases), adjuvant chemotherapy (three cases) or palliative treatment (two cases). The response rate to cisplatin-pemetrexed was 50% (6/12 cases). CRS with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) was performed in 19 patients (upfront in three, after neoadjuvant therapy in 12, or after tumour progression in six patients, including three twice). After a median follow-up of 6.7 years (range, 0-20), five-year overall and event-free survivals were 82.3% (95% CI, confidential interval ((CI), 67.8-99.9) and 45.1% (95% CI, 28.4-71.7), respectively. All patients with MCM are alive after surgery (five patients) and CRS-HIPEC (one patient).

CONCLUSIONS: Paediatric mesothelioma is exceptional and seems to be different from its adult counterpart with few asbestos exposures, more peritoneal primary, and a better outcome. The cisplatin-pemetrexed regimen showed promising efficacy. Relapses could be salvaged with active therapy including CRS-HIPEC.}, } @article {pmid33045471, year = {2020}, author = {Duong, BTV and Wu, L and Green, BJ and Bavaghar-Zaeimi, F and Wang, Z and Labib, M and Zhou, Y and Cantu, FJP and Jeganathan, T and Popescu, S and Pantea, J and de Perrot, M and Kelley, SO}, title = {A liquid biopsy for detecting circulating mesothelial precursor cells: A new biomarker for diagnosis and prognosis in mesothelioma.}, journal = {EBioMedicine}, volume = {61}, number = {}, pages = {103031}, pmid = {33045471}, issn = {2352-3964}, support = {R33 CA204574/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Aged, 80 and over ; Animals ; Asbestos/adverse effects ; *Biomarkers, Tumor ; Cell Line ; Disease Models, Animal ; Female ; Gene Expression Profiling/methods ; Humans ; *Liquid Biopsy/methods/standards ; Male ; Mesothelin ; Mesothelioma/*diagnosis/etiology ; Mice ; Middle Aged ; Neoplasm Grading ; Neoplasm Metastasis ; Neoplasm Staging ; Neoplastic Cells, Circulating/*pathology ; Occupational Exposure/adverse effects ; Prognosis ; Reproducibility of Results ; Transcriptome ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive cancer related to asbestos exposure. Early diagnosis is challenging due to generic symptoms and a lack of biomarkers. We previously demonstrated that mesothelial precursor cells (MPC) characterized by mesothelin (MSLN)+CD90+CD34+ could be implicated in the development of mesothelioma after asbestos exposure. Here, we aimed to determine the clinical significance of detecting MPC in blood for early-stage diagnosis and prognosis of mesothelioma.

METHODS: Due to the rarity of MPC in blood, it is challenging to identify this cell population using conventional techniques. Hence, we have developed a microfluidic liquid biopsy platform called MesoFind that utilizes an immunomagnetic, mesothelin capture strategy coupled with immunofluorescence to identify rare populations of cells at high sensitivity and precision. To validate our technique, we compared this approach to flow cytometry for the detection of MPC in murine blood and lavage samples. Upon successful validation of the murine samples, we then proceeded to examine circulating MPC in 23 patients with MPM, 23 asbestos-exposed individuals (ASB), and 10 healthy donors (HD) to evaluate their prognostic and diagnostic value.

FINDING: MPC were successfully detected in the blood of murine samples using MesoFind but were undetectable with flow cytometry. Circulating MPC were significantly higher in patients with epithelioid MPM compared to HD and ASB. The MPC subpopulation, MSLN+ and CD90+, were upregulated in ASB compared to HD suggesting an early role in pleural damage from asbestos. The MPC subpopulation, MSLN+ and CD34+, in contrast, were detected in advanced MPM and associated with markers of poor prognosis, suggesting a predominant role during cancer progression.

INTERPRETATION: The identification of circulating MPC presents an attractive solution for screening and early diagnosis of epithelioid mesothelioma. The presence of different subtypes of MPC have a prognostic value that could be of assistance with clinical decisions in patients with MPM.

FUNDING: Princess Margaret Hospital Foundation Mesothelioma Research Fund, Toronto General & Western Hospital Foundation.}, } @article {pmid33040390, year = {2021}, author = {Korchevskiy, A}, title = {Using benchmark dose modeling for the quantitative risk assessment: Carbon nanotubes, asbestos, glyphosate.}, journal = {Journal of applied toxicology : JAT}, volume = {41}, number = {1}, pages = {148-160}, doi = {10.1002/jat.4063}, pmid = {33040390}, issn = {1099-1263}, mesh = {Adult ; Asbestos/*toxicity ; Benchmarking ; *Dose-Response Relationship, Drug ; Female ; Glycine/*analogs & derivatives/*toxicity ; Humans ; Male ; Middle Aged ; Nanotubes, Carbon/*toxicity ; Nervous System Diseases/*chemically induced ; Occupational Exposure/adverse effects ; Risk Assessment/*methods ; }, abstract = {Benchmark dose method is one of the most famous quantitative approaches available for toxicological risks prediction. However, it is not fully clear how occupational health professionals can use it for specific workplace scenarios requiring carcinogen risk assessment. The paper explores the hypothesis that benchmark dose method allows to effectively approximate dose-response data on carcinogenic response, providing reasonable estimations of risks in the situations when a choice between more complex models is not warranted for practical purposes. Three case studies were analyzed for the agents with different levels of scientific confidence in human carcinogenicity: carbon nanotubes, amosite asbestos, and glyphosate. For each agent, a critical study was determined, and a dose-response slope factor was quantified, based on the weighted average lower bound benchmark dose. The linear slope factors of 0.111 lifetime excess cases of lung carcinoma per mg/m[3] of MWCNT-7 (in rats exposure equivalent), 0.009 cases of mesothelioma per f/cc-years of cumulative exposure to amosite asbestos, and 0.000094 cases of malignant lymphoma per mg/kg/day of glyphosate (in mice equivalent) were determined. The correlations between the proposed linear predictive models and observed data points were R = 0.96 (R[2] = 0.92) for carbon nanotubes, R = 0.97 (R[2] = 0.95) for amosite asbestos, and R = 0.89 (R[2] = 0.79) for glyphosate. In all three cases, the linear extrapolation yielded comparable level of risk estimations with the "best fit" nonlinear model; for nanoparticles and amosite asbestos, linear estimations were more conservative. By performing a simulation study, it was demonstrated that a weighted average benchmark dose expressed the highest correlation with multistage and quantal-linear models.}, } @article {pmid33037108, year = {2021}, author = {Slomovitz, B and de Haydu, C and Taub, M and Coleman, RL and Monk, BJ}, title = {Asbestos and ovarian cancer: examining the historical evidence.}, journal = {International journal of gynecological cancer : official journal of the International Gynecological Cancer Society}, volume = {31}, number = {1}, pages = {122-128}, doi = {10.1136/ijgc-2020-001672}, pmid = {33037108}, issn = {1525-1438}, mesh = {Asbestos/adverse effects/chemistry/*history ; Biomedical Research/*history/standards ; Causality ; Diagnostic Errors ; Female ; History, 20th Century ; History, 21st Century ; Humans ; Mesothelioma, Malignant/diagnosis ; Observational Studies as Topic ; Ovarian Neoplasms/*diagnosis ; Peritoneal Neoplasms/diagnosis ; Retrospective Studies ; Talc ; }, abstract = {Asbestos recently returned to the spotlight when Johnson & Johnson halted sales of baby powder due to lawsuits claiming that the talc in baby powder may have been contaminated with asbestos, which has been linked to the risk of ovarian cancer development. Although talc and asbestos have some structural similarities, only asbestos is considered causally associated with ovarian cancer by the WHO's International Agency for Research on Cancer. While it is useful to understand the types and properties of asbestos and its oncologic biology, the history of its association with ovarian cancer is largely based on retrospective observational studies in women working in high asbestos exposure environments. In reviewing the literature, it is critical to understand the distinction between associative risk and causality, and to examine the strength of association in the context of how the diagnosis of ovarian cancer is made and how the disease should be distinguished from a similar appearing but unrelated neoplasm, malignant mesothelioma. Based on contextual misinterpretation of these factors, it is imperative to question the International Agency for Research on Cancer's assertion that asbestos has a clear causal inference to ovarian cancer. This has important clinical implications in the way patients are conceivably counseled and provides motivation to continue research to improve the understanding of the association between asbestos and ovarian cancer.}, } @article {pmid33036536, year = {2020}, author = {Song, PP and Sun, XW and Zhang, SQ and Gao, Y and Zhang, H and Chen, YX}, title = {[Clinical analysis of 30 cases with asbestos-related occupational tumors].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {38}, number = {9}, pages = {693-695}, doi = {10.3760/cma.j.cn121094-20190930-00460}, pmid = {33036536}, issn = {1001-9391}, support = {2018-WJZD058//Medical Research Guidance Plan for Qingdao in 2018/ ; }, mesh = {*Asbestos/toxicity ; Humans ; *Lung Neoplasms/epidemiology ; *Mesothelioma/chemically induced/epidemiology ; *Occupational Diseases/epidemiology ; *Occupational Exposure/adverse effects ; *Pleural Neoplasms ; Tomography, X-Ray Computed ; }, abstract = {Asbestos is classified as a Class 1 carcinogen by the International Cancer Organization (IARC) , and almost all types of asbestos are carcinogenic. The clinical data of 30 asbestos-induced occupational tumor patients in Qingdao city from January 2002 to May 2019 were analyzed, including 24 cases of asbestos-induced lung cancer and 6 cases of asbestos-induced malignant mesothelioma. Mesothelioma was significantly worse than lung cancer in terms of malignancy, the survival time of patients is shorter, and the mortality rate was higher. Both its diagnostic methods and treatment methods should be improved. The high incidence of asbestos-caused tumors is coming. It is recommended that workers exposed to asbestos dust should undergo regular chest CT examinations for early detection, early diagnosis and early treatment.}, } @article {pmid33036531, year = {2020}, author = {Jiang, ZQ and Shao, DC and Cheng, YR and Miao, C and Chai, JR and Xu, CM and Yu, M and Wang, J and Li, T and Chen, JQ}, title = {[Detection and comparison of fiber count concentration in processing environment of asbestos and man-made mineral fiber].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {38}, number = {9}, pages = {675-678}, doi = {10.3760/cma.j.cn121094-20191128-00546}, pmid = {33036531}, issn = {1001-9391}, mesh = {*Asbestos/analysis ; China ; Dust/analysis ; Humans ; *Mesothelioma ; Mineral Fibers/analysis ; }, abstract = {Objective: To connect with the measurement data of asbestos dust fiber concentration in foreign countries, improve the accuracy of asbestos fiber detection in China, and understand the dust exposure in the working environment of asbestos and man-made mineral fiber production and processing sites in Zhejiang Province. The fiber count concentrations of working environment in glass fiber, ceramic fiber and asbestos processing plants were measured and compared. Methods: The dust concentration in the working environment of two glass fiber factories, one ceramic fiber factory and eight asbestos products processing factories was measured. The total dust mass concentration was measured according to GBZ/T 192.1-2007, and the fiber count concentration was measured by phase contrast microscope. Kruskal Wallis was used to test and compare the dust concentration in the working environment of each post. The correlation between asbestos mass concentration and fiber count concentration was analyzed by Spearman correlation. Results: Under the phase contrast microscope, there were many short and fine asbestos fibers in the field of vision, and there were many impurities around. The average dust concentration of asbestos processing plant was 3.2 f/ml, and the dust concentration of cotton ginning was the highest (6.68 f/ml) . There was a significantly positive correlation between asbestos fiber count concentration and mass concentration (r=0.535, P=0.033) . The average fiber count concentration of glass fiber factory was 0.001 f/ml, and the highest was 0.005 f/ml. The average fiber count concentration of ceramic fiber factory was 0.001 f/ml, and the highest was 0.006 f/ml. Conclusion: The fiber count concentration in the working environment of asbestos factory in Zhejiang Province is obviously over the standard, which is one of the important reasons for the high incidence of mesothelioma in this area. Short and small asbestos fibers are easy to be ignored when counting. It is necessary to improve the actual operation process of fiber counting to form a laboratory standard in China.}, } @article {pmid33032525, year = {2020}, author = {Kumagai-Takei, N and Nishimura, Y and Maeda, M and Hayashi, H and Matsuzaki, H and Lee, S and Yoshitome, K and Ito, T and Otsuki, T}, title = {Effect of asbestos exposure on differentiation and function of cytotoxic T lymphocytes.}, journal = {Environmental health and preventive medicine}, volume = {25}, number = {1}, pages = {59}, pmid = {33032525}, issn = {1347-4715}, support = {H18-1-3-3-1//Japan Science and Technology Agency/ ; 19659153//Japan Society for the Promotion of Science/ ; 20390178//Japan Society for the Promotion of Science/ ; 20890270//Japan Society for the Promotion of Science/ ; 21659161//Japan Society for the Promotion of Science/ ; 23790679//Japan Society for the Promotion of Science/ ; 25860470//Japan Society for the Promotion of Science/ ; 16K09114//Japan Society for the Promotion of Science/ ; Tokutei Kenkyu Josei I, 2008//Takeda Science Foundation/ ; 21-107//Kawasaki Medical School/ ; 21-401//Kawasaki Medical School/ ; 20-411I//Kawasaki Medical School/ ; 22-A29//Kawasaki Medical School/ ; 23B66//Kawasaki Medical School/ ; 23P3//Kawasaki Medical School/ ; 26B39//Kawasaki Medical School/ ; 29B051//Kawasaki Medical School/ ; Kyoiku Kenkyu Josei, 2009//The Kawasaki Foundation for Medical Science and Medical Welfare/ ; Kenkyu Josei, 2009//The Ryobi Teien Memory Foundation/ ; Tokubetsu Dengen Syozai Ken Kagaku Gijyutsu Sinkou Jigyou Kenkyu Itaku, 2010-2012//Okayama prefecture/ ; }, mesh = {Asbestos/*toxicity ; Asbestos, Serpentine/toxicity ; Cell Differentiation/*drug effects ; Cell Proliferation/*drug effects ; Humans ; Lung Neoplasms/*immunology ; Mesothelioma/*immunology ; Mesothelioma, Malignant ; T-Lymphocytes, Cytotoxic/*drug effects/immunology ; }, abstract = {Asbestos exposure is known to cause malignant mesothelioma, which is associated with poor prognosis. We focused on and examined the effect of asbestos exposure on the differentiation and function of cytotoxic T lymphocytes (CTLs). CTLs have the ability to specifically attack tumor cells after being differentiated from naïve CD8[+] T cells following antigen stimulation. Exposure to chrysotile B asbestos suppressed the differentiation of CTLs during the mixed lymphocyte reaction (MLR) and was associated with a decrease in proliferation of CD8[+] T cells. Additionally, in an effort to investigate the mechanism associated with suppressed CTL differentiation upon exposure to asbestos, we focused on IL-2, a cytokine involved in T cell proliferation. Our findings indicated that insufficient levels of IL-2 are not the main cause for the suppressed induction of CTLs by asbestos exposure, although they suggest potential improvement in the suppressed CTL function. Furthermore, the functional properties of peripheral blood CD8[+] lymphocytes from asbestos-exposed individuals with pleural plaque (PP) and patients with malignant mesothelioma (MM) were examined. MM patients showed lower perforin levels in CD8[+] lymphocytes following stimulation compared with PP-positive individuals. The production capacity of IFN-γ in the MM group tended to be lower compared with healthy volunteers or PP-positive individuals. In an effort to determine whether chronic and direct asbestos exposure affected the function of CD8[+] T cells, cultured human CD8[+] T cells were employed as an in vitro model and subjected to long-term exposure to chrysotile (CH) asbestos. This resulted in decreased levels of intracellular perforin and secreted IFN-γ. Those findings underlie the possibility that impaired CD8[+] lymphocyte function is caused by asbestos exposure, which fail to suppress the development of MM. Our studies therefore reveal novel effects of asbestos exposure on CTLs, which might contribute towards the development and implementation of an effective strategy for the prevention and cure of malignant mesothelioma.}, } @article {pmid33032291, year = {2020}, author = {Zhang, X and Yang, L and Chen, W and Kong, M}, title = {Identification of Potential Hub Genes and Therapeutic Drugs in Malignant Pleural Mesothelioma by Integrated Bioinformatics Analysis.}, journal = {Oncology research and treatment}, volume = {43}, number = {12}, pages = {656-671}, doi = {10.1159/000510534}, pmid = {33032291}, issn = {2296-5262}, mesh = {Antineoplastic Agents/therapeutic use ; Biomarkers, Tumor/genetics/metabolism ; Computational Biology/*methods ; Databases, Genetic ; Down-Regulation ; Drug Discovery/*methods ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; *Genes, Neoplasm ; Humans ; Mesothelioma, Malignant/*drug therapy/*genetics ; Microarray Analysis ; Molecular Targeted Therapy/methods ; Peroxisome Proliferator-Activated Receptors/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Prognosis ; Protein Interaction Maps/genetics ; Up-Regulation ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is closely linked to asbestos exposure and is an extremely aggressive tumor with poor prognosis.

OBJECTIVE: Our study aimed to elucidate hub genes and potential drugs in MPM by integrated bioinformatics analysis.

METHODS: GSE42977 was download from the Gene Expression Omnibus (GEO) database; the differentially expressed genes (DEGs) with adj.p value <0.05 and |logFC| ≥2 were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed by DAVID database. The STRING database was used to construct a protein-protein interaction network, and modules analysis and hub genes acquisition were performed by Cytoscape. The Gene Expression Profiling Interactive Analysis (GEPIA) database was used to assess the impact of hub genes on the prognosis of MPM patients. The Drug-Gene Interaction database (DGIdb) was used to select the related drugs.

RESULTS: A total of 169 upregulated and 70 downregulated DEGs were identified. These DEGs are enriched in the pathway of extracellular matrix-receptor interaction, focal adhesion, PI3K-Akt signaling pathway, and PPAR signaling pathway. Finally, 10 hub genes (CDC20, CDK1, UBE2C, TOP2A, CCNB2, NUSAP1, KIF20A, AURKA, CEP55, and ASPM) were identified, which are considered to be closely related to the poor prognosis of MPM. In addition, 119 related drugs that may have a therapeutic effect on MPM were filtered out.

CONCLUSION: These discovered genes and small-molecule drugs provide some new ideas for further research on MPM.}, } @article {pmid33020398, year = {2020}, author = {Iannuzzi, CA and Indovina, P and Forte, IM and Di Somma, S and Malfitano, AM and Bruno, M and Portella, G and Pentimalli, F and Giordano, A}, title = {Pharmacological Inhibition of WEE1 Potentiates the Antitumoral Effect of the dl922-947 Oncolytic Virus in Malignant Mesothelioma Cell Lines.}, journal = {International journal of molecular sciences}, volume = {21}, number = {19}, pages = {}, pmid = {33020398}, issn = {1422-0067}, mesh = {Adenoviridae/genetics ; Apoptosis/drug effects ; Asbestos/toxicity ; Cell Cycle Proteins/*antagonists & inhibitors/genetics/pharmacology ; Cell Line, Tumor ; Cell Survival/*drug effects ; DNA Damage/drug effects ; Humans ; Mesothelioma, Malignant/chemically induced/*drug therapy/genetics/virology ; Oncolytic Virotherapy ; Oncolytic Viruses/genetics ; Phosphorylation/drug effects ; Protein Kinase Inhibitors ; Protein-Tyrosine Kinases/*antagonists & inhibitors/genetics ; Pyrazoles/*pharmacology ; Pyrimidinones/*pharmacology ; }, abstract = {Malignant mesothelioma (MM) is a very aggressive asbestos-related cancer, for which no therapy proves to be effective. We have recently shown that the oncolytic adenovirus dl922-947 had antitumor effects in MM cell lines and murine xenografts. Previous studies demonstrated that dl922-947-induced host cell cycle checkpoint deregulation and consequent DNA lesions associated with the virus efficacy. However, the cellular DNA damage response (DDR) can counteract this virus action. Therefore, we assessed whether AZD1775, an inhibitor of the G2/M DNA damage checkpoint kinase WEE1, could enhance MM cell sensitivity to dl922-947. Through cell viability assays, we found that AZD1775 synergized with dl922-947 selectively in MM cell lines and increased dl922-947-induced cell death, which showed hallmarks of apoptosis (annexinV-positivity, caspase-dependency, BCL-XL decrease, chromatin condensation). Predictably, dl922-947 and/or AZD1775 activated the DDR, as indicated by increased levels of three main DDR players: phosphorylated histone H2AX (γ-H2AX), phospho-replication protein A (RPA)32, phospho-checkpoint kinase 1 (CHK1). Dl922-947 also increased inactive Tyr-15-phosphorylated cyclin-dependent kinase 1 (CDK1), a key WEE1 substrate, which is indicative of G2/M checkpoint activation. This increase in phospho-CDK1 was effectively suppressed by AZD1775, thus suggesting that this compound could, indeed, abrogate the dl922-947-induced DNA damage checkpoint in MM cells. Overall, our data suggest that the dl922-947-AZD1775 combination could be a feasible strategy against MM.}, } @article {pmid33014860, year = {2020}, author = {Rozitis, E and Johnson, B and Cheng, YY and Lee, K}, title = {The Use of Immunohistochemistry, Fluorescence in situ Hybridization, and Emerging Epigenetic Markers in the Diagnosis of Malignant Pleural Mesothelioma (MPM): A Review.}, journal = {Frontiers in oncology}, volume = {10}, number = {}, pages = {1742}, pmid = {33014860}, issn = {2234-943X}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive asbestos related disease that is generally considered to be difficult to diagnose, stage and treat. The diagnostic process is continuing to evolve and requires highly skilled pathology input, and generally an extensive list of biomarkers for definitive diagnosis. Diagnosis of MPM requires histological evidence of invasion by malignant mesothelial cells often confirmed by various immunohistochemical biomarkers in order to separate it from pleural metastatic carcinoma. Often when invasion of neoplastic mesothelial cells into adjacent tissue is not apparent, further immunohistochemical testing - namely BAP1 and MTAP, as well as FISH testing for loss of p16 (CDKN2A) are used to separate reactive mesothelial proliferation due to benign processes, from MPM. Various combinations of these markers, such as BAP1 and/or MTAP immunohistochemistry alongside FISH testing for loss of p16, have shown excellent sensitivity and specificity in the diagnosis of MPM. Additionally, over the recent years, research into epigenetic marker use in the diagnosis of MPM has gained momentum. Although still in their research stages, various markers in DNA methylation, long non-coding RNA, micro RNA, circular RNA, and histone modifications have all been found to support diagnosis of MPM with generally good sensitivity and specificity. Many of these studies are however, limited by small sample sizes or other study limitations and further research into the area would be beneficial. Epigenetic markers show promise for use in the future to facilitate the diagnosis of MPM.}, } @article {pmid33012432, year = {2020}, author = {Ripley, RT}, title = {Extended Pleurectomy and Decortication for Malignant Pleural Mesothelioma.}, journal = {Thoracic surgery clinics}, volume = {30}, number = {4}, pages = {451-460}, doi = {10.1016/j.thorsurg.2020.07.002}, pmid = {33012432}, issn = {1558-5069}, mesh = {Humans ; Mesothelioma, Malignant/*surgery ; Pleura/*surgery ; Pleural Neoplasms/surgery ; Thoracic Surgical Procedures/*methods ; Treatment Outcome ; }, abstract = {Extended pleurectomy and decortication (ePD) is a difficult operation performed for the surgical resection of malignant pleural mesothelioma that can achieve a macroscopic complete resection with preservation of the lung. With lower perioperative mortality, similar long-term survival, and better tolerance in patients with lower performance status, ePD has become the preferred operation rather than extrapleural pneumonectomy despite lack of a direct comparison. As ePD has become more popular, international collaboration is underway to create surgical guidelines based on collection of operative data. These efforts will improve the safety and standardization of this operation.}, } @article {pmid33012429, year = {2020}, author = {Pass, HI and Alimi, M and Carbone, M and Yang, H and Goparaju, CM}, title = {Mesothelioma Biomarkers: Discovery in Search of Validation.}, journal = {Thoracic surgery clinics}, volume = {30}, number = {4}, pages = {395-423}, doi = {10.1016/j.thorsurg.2020.08.001}, pmid = {33012429}, issn = {1558-5069}, mesh = {Asbestos/adverse effects ; *Biomarkers, Tumor/analysis/blood/genetics/metabolism ; Calbindin 2/analysis/blood/genetics/metabolism ; Extracellular Matrix Proteins/analysis/blood/genetics/metabolism ; HMGB1 Protein/analysis/blood/genetics/metabolism ; Humans ; Mesothelioma, Malignant/*blood/chemistry/genetics/metabolism ; Multidrug Resistance-Associated Proteins/analysis/*blood/genetics/metabolism ; Pleural Neoplasms/blood/chemistry/genetics/metabolism ; Prognosis ; Proteomics ; }, abstract = {Malignant pleural mesothelioma (MPM) is an asbestos-related neoplasm that can only be treated successfully when correctly diagnosed and treated early. The asbestos-exposed population is a high-risk group that could benefit from sensitive and specific blood- or tissue-based biomarkers. We review recent work with biomarker development in MPM and literature of the last 20 years on the most promising blood- and tissue-based biomarkers. Proteomic, genomic, and epigenomic platforms are covered. SMRP is the only validated blood-based biomarker with diagnostic, monitoring and prognostic value. To strengthen development and testing of MPM biomarkers, cohorts for validation must be established by enlisting worldwide collaborations.}, } @article {pmid33012428, year = {2020}, author = {Wadowski, B and De Rienzo, A and Bueno, R}, title = {The Molecular Basis of Malignant Pleural Mesothelioma.}, journal = {Thoracic surgery clinics}, volume = {30}, number = {4}, pages = {383-393}, pmid = {33012428}, issn = {1558-5069}, support = {R01 CA120528/CA/NCI NIH HHS/United States ; }, mesh = {Asbestos/adverse effects ; Computational Biology/methods ; Epigenesis, Genetic ; Gene Expression ; High-Throughput Nucleotide Sequencing ; Humans ; Mesothelioma, Malignant/etiology/*genetics ; Pleural Neoplasms/etiology/genetics ; Transcriptome ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare, aggressive malignancy of the pleural lining associated with asbestos exposure in greater than 80% of cases. It is characterized by molecular heterogeneity both between patients and within individual tumors. Next-generation sequencing technology and novel computational techniques have resulted in a greater understanding of the epigenetic, genetic, and transcriptomic hallmarks of MPM. This article reviews these features and discusses the implications of advances in MPM molecular biology in clinical practice.}, } @article {pmid32999071, year = {2020}, author = {Xue, J and Patergnani, S and Giorgi, C and Suarez, J and Goto, K and Bononi, A and Tanji, M and Novelli, F and Pastorino, S and Xu, R and Caroccia, N and Dogan, AU and Pass, HI and Tognon, M and Pinton, P and Gaudino, G and Mak, TW and Carbone, M and Yang, H}, title = {Asbestos induces mesothelial cell transformation via HMGB1-driven autophagy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {117}, number = {41}, pages = {25543-25552}, pmid = {32999071}, issn = {1091-6490}, support = {R01 CA198138/CA/NCI NIH HHS/United States ; R01 CA237235/CA/NCI NIH HHS/United States ; R01 ES030948/ES/NIEHS NIH HHS/United States ; U01 CA214195/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Animals ; Asbestos/*adverse effects ; Autophagy/*drug effects ; Cell Transformation, Neoplastic/*chemically induced ; Cells, Cultured ; Epithelial Cells/cytology/metabolism ; HMGB1 Protein/*metabolism ; Humans ; Male ; Mesothelioma/*metabolism ; Mice ; Mice, Knockout ; Middle Aged ; Occupational Exposure ; }, abstract = {Asbestos causes malignant transformation of primary human mesothelial cells (HM), leading to mesothelioma. The mechanisms of asbestos carcinogenesis remain enigmatic, as exposure to asbestos induces HM death. However, some asbestos-exposed HM escape cell death, accumulate DNA damage, and may become transformed. We previously demonstrated that, upon asbestos exposure, HM and reactive macrophages releases the high mobility group box 1 (HMGB1) protein that becomes detectable in the tissues near asbestos deposits where HMGB1 triggers chronic inflammation. HMGB1 is also detectable in the sera of asbestos-exposed individuals and mice. Searching for additional biomarkers, we found higher levels of the autophagy marker ATG5 in sera from asbestos-exposed individuals compared to unexposed controls. As we investigated the mechanisms underlying this finding, we discovered that the release of HMGB1 upon asbestos exposure promoted autophagy, allowing a higher fraction of HM to survive asbestos exposure. HMGB1 silencing inhibited autophagy and increased asbestos-induced HM death, thereby decreasing asbestos-induced HM transformation. We demonstrate that autophagy was induced by the cytoplasmic and extracellular fractions of HMGB1 via the engagement of the RAGE receptor and Beclin 1 pathway, while nuclear HMGB1 did not participate in this process. We validated our findings in a novel unique mesothelial conditional HMGB1-knockout (HMGB1-cKO) mouse model. Compared to HMGB1 wild-type mice, mesothelial cells from HMGB1-cKO mice showed significantly reduced autophagy and increased cell death. Autophagy inhibitors chloroquine and desmethylclomipramine increased cell death and reduced asbestos-driven foci formation. In summary, HMGB1 released upon asbestos exposure induces autophagy, promoting HM survival and malignant transformation.}, } @article {pmid32988786, year = {2020}, author = {Cattaneo, M and Mendogni, P and Damarco, F and Tosi, D}, title = {Spontaneous diaphragmatic rupture following neoadjuvant chemotherapy and cytoreductive surgery in malignant pleural mesothelioma: A case report and review of the literature.}, journal = {International journal of surgery case reports}, volume = {77S}, number = {Suppl}, pages = {S85-S87}, pmid = {32988786}, issn = {2210-2612}, abstract = {INTRODUCTION: Diaphragmatic rupture (DR) is an acquired diaphragmatic defect that can cause herniation of abdominal organs into the chest. It is usually a trauma-related lesion, but rarely it can occur spontaneously. Every DR with abdominal herniation should be considered a surgical emergency.

PRESENTATION OF CASE: A 61-year-old male patient, with previous exposure to asbestos, was diagnosed of Stage Ib malignant pleural mesothelioma (MPM). He underwent neo-adjuvant chemotherapy (three cycle of cisplatin-pemetrexed combination) and a cytoreductive surgery with pleurectomy/decortication. Post-operative course was characterized by prolonged air-leakage (PAL). After three months, during a follow-up CT-scan, a spontaneous diaphragmatic rupture (SDR) with gastric herniation was detected and treated by a laparascopic diaphragmatic repair and suture.

DISCUSSION: Spontaneous diaphragmatic rupture (SDR) is an extremely rare injury of the diaphragm (less than 1% of all DR). In this case, potential predisposing factors for SDR could be: presence of diaphragmatic "locus minoris resistentiae" due to thinning of the diaphragm and increase tissue fragility after neo-adjuvant chemotherapy and diaphragmatic pleural stripping; increased thoraco-abdominal pressure gradient due to PAL and residual pleural space. Thus, we confirmed the feasibility and safety of the laparoscopic approach.

CONCLUSION: We highlight the multifactor etiopathology, the challenging diagnosis and the importance of a prompt treatment of SDR.}, } @article {pmid32977478, year = {2020}, author = {Kumagai-Takei, N and Lee, S and Srinivas, B and Shimizu, Y and Sada, N and Yoshitome, K and Ito, T and Nishimura, Y and Otsuki, T}, title = {The Effects of Asbestos Fibers on Human T Cells.}, journal = {International journal of molecular sciences}, volume = {21}, number = {19}, pages = {}, pmid = {32977478}, issn = {1422-0067}, mesh = {Asbestos/*toxicity ; CD8-Positive T-Lymphocytes/*immunology/pathology ; Humans ; *Immunity, Cellular ; Mesothelioma, Malignant/chemically induced/*immunology/pathology ; T-Lymphocytes, Regulatory/*immunology/pathology ; }, abstract = {Asbestos exposure causes malignant tumors such as lung cancer and malignant mesothelioma. The effects of asbestos fibers on immunocompetent cells, however, have not been well studied. Asbestos physically comprises a fibrous substance, which differs from silica particles which are a particulate substance, although chemically it is a mineral silicate. Since silicosis patients previously exposed to silica particles often suffer from lung and autoimmune diseases, it is clear that silica exposure impairs immune tolerance. Similarly, asbestos may alter the immune system in asbestos-exposed individuals. Given that malignant tumors can result following exposure to asbestos, the attenuation of anti-tumor immunity in cases of asbestos exposure is an important area of investigation. We observed the effect of asbestos fibers on T lymphocytes, such as CD8+ cytotoxic T lymphocytes (CTLs), CD4+ helper T (Th), and regulatory T (Treg) cells, and showed that anti-tumor immunity was attenuated, as demonstrated in a system that stimulates fresh cells isolated from peripheral blood in vitro and a system that is continuously exposed to a cell line. In this manuscript, we introduce the experiments and results of studies on CTLs, as well as Th and Treg cells, and discuss how future changes in immunocompetent cells induced by asbestos fibers can be clinically linked.}, } @article {pmid32971078, year = {2020}, author = {Lysaniuk, B and Cely-García, MF and Mazzeo, A and Marsili, D and Pasetto, R and Comba, P and Ramos-Bonilla, JP}, title = {Where are the landfilled zones? Use of historical geographic information and local spatial knowledge to determine the location of underground asbestos contamination in Sibaté (Colombia).}, journal = {Environmental research}, volume = {191}, number = {}, pages = {110182}, doi = {10.1016/j.envres.2020.110182}, pmid = {32971078}, issn = {1096-0953}, mesh = {*Asbestos ; Cities ; Colombia ; Environmental Exposure ; *Occupational Exposure ; Waste Disposal Facilities ; }, abstract = {INTRODUCTION: Sibaté is a municipality located in the central region of Colombia, where the first asbestos-cement facility of the country has been in operation since 1942. Both a malignant pleural mesothelioma cluster and landfilled zones with the presence of an underground friable asbestos layer have been identified in Sibaté. There is still limited knowledge regarding the history of the construction of landfilled zones, and what kinds of materials were deposited. The current study aims to improve our understanding of the history and characteristics of the landfilled zones present in Sibaté.

METHODS: Two participatory workshops with inhabitants of Sibaté were conducted to determine when the landfilled zones were built and their location. Information collected in participatory workshops was crossed with both topographic maps and aerial photographs, giving special attention to zones within the urban area of the municipality that in the past were inundated with water from El Muña Reservoir. An opportunistic soil sampling campaign was conducted in suspected landfilled zones that had not been previously sampled, during the replacement of pipelines of the drainage system ordered by the municipality.

RESULTS: The analysis of historical topographic maps, combined with the interpretation of aerial photographs, confirmed the disposal of residues in areas that were previously inundated with water from El Muña Reservoir, creating landfilled zones in the urban area of Sibaté. On top of these landfilled zones, a football stadium and a football field with an athletic track were built. The location of landfilled zones identified using geographic analysis was similar to the location identified analyzing maps constructed by inhabitants of Sibaté in participatory workshops. The four soil samples collected during an opportunistic sampling campaign confirmed the presence in new locations of the underground friable asbestos layer discovered in previous studies.

DISCUSSION: Based on the extension of the landfilled zones, the presence of friable asbestos in these areas, and the close proximity to a school and residential dwellings, there could have been major dispersion events of asbestos fibers in the urban area of Sibaté during the disposal of residue materials and the construction of the landfilled zones. Thus, important asbestos exposures may have occurred among residents of Sibaté, which is aggravated by the fact that during those years, more than 50% of the population of Sibaté was 25 years old or younger. Although the results of the current study improved our understanding of the processes and chronology associated with the landfilled zones, the uncertainty regarding their exact location remains significant. It is important to continue investigating the adverse health effects resulting from this potential asbestos exposure source.}, } @article {pmid32967259, year = {2020}, author = {Chimed-Ochir, O and Arachi, D and Driscoll, T and Lin, RT and Takala, J and Takahashi, K}, title = {Burden of Mesothelioma Deaths by National Income Category: Current Status and Future Implications.}, journal = {International journal of environmental research and public health}, volume = {17}, number = {18}, pages = {}, pmid = {32967259}, issn = {1660-4601}, mesh = {Asbestos/toxicity ; Global Health ; Humans ; *Income ; *Mesothelioma/economics/mortality ; Reproducibility of Results ; }, abstract = {Background: This study compares estimates of the global-level mesothelioma burden with a focus on how existing national mortality data were utilized and further assesses the interrelationship of country-level mesothelioma burden and asbestos use with national income status. Methods: Country-level mesothelioma deaths in the WHO Mortality Database as of December 2019 were analyzed by national income category of countries in terms of data availability and reliability. Numbers of mesothelioma deaths from the study of Odgerel et al. were reanalyzed to assess country-level mesothelioma death burdens by national income status. Results: Among 80 high-income countries, 54 (68%) reported mesothelioma to the WHO and 26 (32%) did not, and among 60 upper middle-income countries, the respective numbers (proportions) were 39 (65%) countries and 21 (35%) countries, respectively. In contrast, among 78 low- and lower middle-income countries, only 11 (14%) reported mesothelioma deaths while 67 (86%) did not. Of the mesothelioma deaths, 29,854 (78%) were attributed to high- and upper middle-income countries, and 8534 (22%) were attributed to low- and lower middle- income countries. Conclusions: The global mesothelioma burden, based on reported numbers, is currently shouldered predominantly by high-income countries; however, mesothelioma burdens will likely manifest soon in upper middle-income and eventually in low and lower middle-income countries.}, } @article {pmid32966235, year = {2021}, author = {Cheng, TJ and More, SL and Maddaloni, MA and Fung, ES}, title = {Evaluation of potential gastrointestinal carcinogenicity associated with the ingestion of asbestos.}, journal = {Reviews on environmental health}, volume = {36}, number = {1}, pages = {15-26}, doi = {10.1515/reveh-2020-0061}, pmid = {32966235}, issn = {2191-0308}, mesh = {Animals ; Asbestos/*toxicity ; Gastrointestinal Neoplasms/chemically induced/*epidemiology/pathology ; Humans ; Mesothelioma/chemically induced/epidemiology/pathology ; }, abstract = {The inhalation of asbestos, depending on the fiber type and dose, may be associated with the development of mesothelioma and other asbestos-related diseases. However, little is known about the potential adverse effects associated with the ingestion of asbestos. Evidence of asbestos fibers released from asbestos-cement pipes used in water distribution systems has led to concerns of potentially contaminated drinking water. The purpose of this study is to determine whether ingestion of asbestos fibers may lead to cancerous effects on the gastrointestinal (GI) tract. Data from animal and human studies were analyzed using a weight-of-evidence approach to evaluate the potential risk of GI cancers associated with asbestos ingestion. Seventeen human and 23 animal studies were identified and evaluated in this study. Animal studies were conducted in multiple species with inconsistent dosing protocols. Overall, animal studies reported that the asbestos fibers, irrespective of fiber type and dose, failed to produce any definitive GI carcinogenic effect. The 17 identified human epidemiological studies reported the ingestion of asbestos-contaminated water with concentrations from 1 to 71,350 million fibers per liter (MFL). A majority of the epidemiology studies reported statistically significant increases in multiple GI-specific cancers. However, these findings are confounded due to several critical study limitations including flawed study design, small sample size, selection bias, lack of individual exposure history, lack of adequate latency, and the inability to account for confounders including occupational history, diet, and smoking history. Based on our weight-of-evidence assessment, there is insufficient evidence of causality between the ingestion of asbestos and an increased incidence of GI cancers.}, } @article {pmid32963780, year = {2020}, author = {Ohnishi, Y and Fujii, T and Sakamoto, T and Watanabe, M and Motohashi, T and Kubo, H and Nakajima, M}, title = {Malignant mesothelioma metastatic to the oral region and latest topics (Review).}, journal = {Molecular and clinical oncology}, volume = {13}, number = {5}, pages = {61}, pmid = {32963780}, issn = {2049-9450}, abstract = {Malignant mesothelioma (MM) is a rare neoplasm with poor prognosis that usually develops after exposure to asbestos, and is characterised by aggressive local invasion and metastatic spread. While metastasis to the oral cavity is very rare, a total of 23 cases of MM metastasising to the oral cavity were identifed. Among those, the tongue was the most common site of metastasis (39.1%), and frequently involved the epithelioid MM cell type. Recent studies have elucidated the mechanisms underlying the development of MM. Chronic inflammation has been implicated in promoting MM growth and was shown to play a key role by driving the release of high mobility group box protein 1 following asbestos deposition. Inherited heterozygous germline mutations in the deubiquitylase BRCA-associated protein 1 were shown to increase the incidence of MM in some families. Infection by the simian virus 40 was also found to be associated with the occurrence of MM. Moreover, the increasing incidence rates of MM, together with its propensity to metastasise to the oral cavity, indicate that clinicians and pathologists should be highly aware of this disease. Furthermore, identification of novel serum biomarkers would enable better screening and treatment of MM, and improve the survival outcomes.}, } @article {pmid32959879, year = {2021}, author = {Giles Murphy, T and Bornstein, S and Oudyk, J and Demers, PA}, title = {A Quantitative Retrospective Exposure Assessment for Former Chrysotile Asbestos Miners and Millers from Baie Verte, NL, Canada.}, journal = {Annals of work exposures and health}, volume = {65}, number = {1}, pages = {113-126}, pmid = {32959879}, issn = {2398-7316}, support = {//CIHR/Canada ; }, mesh = {*Asbestos/adverse effects ; Asbestos, Serpentine ; Canada ; Humans ; Italy ; *Mesothelioma/chemically induced/epidemiology ; *Occupational Diseases/chemically induced/epidemiology ; *Occupational Exposure ; Quebec ; Retrospective Studies ; }, abstract = {Despite numerous studies of asbestos workers in the epidemiologic literature, there are very few cohort studies of chrysotile asbestos miners/millers that include high-quality retrospective exposure assessments. As part of the creation of the Baie Verte Miners' Registry in 2008, a two-dimensional job exposure matrix (JEM) was developed for estimating asbestos exposures for former chrysotile asbestos miners/millers. Industrial hygiene data collected between 1963 and 1994 were analysed to assess validity for use in a retrospective exposure assessment and epidemiologic study. Registered former employees were divided into 52 exposure groups (EGs) based on job title and department and mean asbestos concentrations were calculated for each EG. The resulting exposure estimates were linked to individual registrants' work histories allowing for the calculation of cumulative asbestos exposure for each registrant. The distribution of exposure for most EGs (82.6%) could be described as fitting a log-normal distribution, although variability within some EGs (55%) exceeded a geometric standard deviation (GSD) of 2.5. Overall, the data used to create EGs in the development of the JEM were deemed to be of adequate quality for estimating cumulative asbestos exposures for the former employees of the Baie Verte asbestos mine/mill. The variability between workers in the same job was often high and is an important factor to be considered when using estimates of cumulative asbestos exposure to adjudicate compensation claims. The exposures experienced in this cohort were comparable to those of other chrysotile asbestos miners/millers cohorts, specifically Italian and Québec cohorts.}, } @article {pmid32944078, year = {2020}, author = {Wahlbuhl, E and Liehr, T and Rincic, M and Azawi, S}, title = {Cytogenomic characterization of three murine malignant mesothelioma tumor cell lines.}, journal = {Molecular cytogenetics}, volume = {13}, number = {}, pages = {43}, pmid = {32944078}, issn = {1755-8166}, abstract = {BACKGROUND: Malignant mesothelioma (MM) is a rare aggressive cancer primary located in pleura and lung. MMs can be divided into biphasic, epithelioid and sarcomatoid subtypes. In majority of cases MMs are induced by asbestos fiber exposure. As latency period after asbestos exposure ranges between ~ 10 and 60 years MMs are mainly observed in elder people. Human MM, being a rare tumor type, lacks detailed cytogenetic data, while molecular genetic studies have been undertaken more frequently. However, murine MM cell lines are also regularly applied to get more insight into MM biology and to test new therapy strategies.

RESULTS: Here the murine MM cell lines AB1, AB22 and AC29 were studied by molecular cytogenetics and molecular karyotyping. Interestingly, yet there were no genetic or genomic studies undertaken for these already in 1992 established cell lines. The obtained data on genomic imbalances in these murine cell lines was translated into the human genome as previously reported based on human and murine genomic browsers.

CONCLUSIONS: It turned out that all three cell lines showed high similarities in copy number variants as observed typically in human MM. Also, all three cell lines were most similar to human epithelioid MMs, and should be used as models therefore.}, } @article {pmid32933580, year = {2020}, author = {Fisher, SA and Peddle-McIntyre, CJ and Burton, K and Newton, RU and Marcq, E and Lake, RA and Nowak, AK}, title = {Voluntary exercise in mesothelioma: effects on tumour growth and treatment response in a murine model.}, journal = {BMC research notes}, volume = {13}, number = {1}, pages = {435}, pmid = {32933580}, issn = {1756-0500}, support = {CRE APP1107043//National Health and Medical Research Council/ ; Health Research Fund//Slater & Gordon/ ; KotK_UA/2018/11519/1//Kom Op Tegen Kanker (Stand Up to Cancer)/ ; hShort-Term Research Fellowship April 2019//European Respiratory Society-ERS/ ; }, mesh = {Animals ; *Asbestos/toxicity ; Disease Models, Animal ; *Mesothelioma/chemically induced/therapy ; *Mesothelioma, Malignant ; Mice ; *Occupational Exposure ; }, abstract = {OBJECTIVE: There is substantial evidence that exercise can safely reduce the risk of cancer and improve survival in different human cancer populations. Long latency periods associated with carcinogen-induced cancers like asbestos induced mesothelioma provide an opportunity to implement exercise as an intervention to delay or prevent disease development. However, there are limited studies investigating the ability of exercise to prevent or delay cancer, and exercise as a preventive strategy has never been assessed in models with a known carcinogen. We investigated the potential of voluntary exercise (VE) to delay development of asbestos related disease (ARD) in our well-characterised, asbestos induced MexTAg model of mesothelioma.

RESULTS: Asbestos exposed MexTAg mice were given continuous or delayed access to VE and ARD assessed over time. We found that the addition of VE did not affect ARD development in asbestos exposed MexTAg mice. However, non-asbestos exposed, aged matched control mice participated in significantly more VE behaviours, suggesting subclinical development of ARD after asbestos exposure had a greater impact on VE participation than age alone. These data highlight the importance of model choice and the potential limitation that some pre-clinical studies may not accurately represent the clinical paradigm, particularly in the context of prevention studies.}, } @article {pmid32929059, year = {2020}, author = {Costa, C and Indovina, P and Mattioli, E and Forte, IM and Iannuzzi, CA and Luzzi, L and Bellan, C and De Summa, S and Bucci, E and Di Marzo, D and De Feo, M and Mutti, L and Pentimalli, F and Giordano, A}, title = {P53-regulated miR-320a targets PDL1 and is downregulated in malignant mesothelioma.}, journal = {Cell death & disease}, volume = {11}, number = {9}, pages = {748}, pmid = {32929059}, issn = {2041-4889}, mesh = {B7-H1 Antigen/*genetics/*metabolism ; Cell Line, Tumor ; Cell Movement/physiology ; Cell Proliferation/physiology ; Down-Regulation ; HEK293 Cells ; Humans ; Mesothelioma, Malignant/genetics/*metabolism/pathology ; MicroRNAs/genetics/*metabolism ; Transfection ; Tumor Suppressor Protein p53/genetics/*metabolism ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive cancer, related to asbestos exposure, which has a dismal prognosis. MPM diagnosis is late and often challenging, suggesting the need to identify more reliable molecular biomarkers. Here, we set out to identify differentially expressed miRNAs in epithelioid, biphasic, and sarcomatoid MPMs versus normal mesothelium and explored specific miRNA contribution to mesothelial tumorigenesis. We screened an LNA™-based miRNA-microrray with 14 formalin-fixed paraffin-embedded (FFPE) MPMs and 6 normal controls. Through real-time qRT-PCR we extended the analysis of a miRNA subset and further investigated miR-320a role through state-of-the-art techniques. We identified 16 upregulated and 32 downregulated miRNAs in MPMs versus normal tissue, including the previously identified potential biomarkers miR-21, miR-126, miR-143, miR-145. We showed in an extended series that miR-145, miR-10b, and miR-320a levels can discriminate tumor versus controls with high specificity and sensitivity. We focused on miR-320a because other family members were found downregulated in MPMs. However, stable miR-320a ectopic expression induced higher proliferation and migration ability, whereas miR-320a silencing reduced these processes, not supporting a classic tumor-suppressor role in MPM cell lines. Among putative targets, we found that miR-320a binds the 3'-UTR of the immune inhibitory receptor ligand PDL1 and, consistently, miR-320a modulation affects PDL1 levels in MPM cells. Finally, we showed that p53 over-expression induces the upregulation of miR-320a, along with miR-200a and miR-34a, both known to target PDL1, and reduces PDL1 levels in MPM cells. Our data suggest that PDL1 expression might be due to a defective p53-regulated miRNA response, which could contribute to MPM immune evasion or tumorigenesis through tumor-intrinsic roles.}, } @article {pmid32927122, year = {2021}, author = {Reardon, ES and Shukla, V and Xi, S and Gara, SK and Liu, Y and Straughan, D and Zhang, M and Hong, JA and Payabyab, EC and Kumari, A and Richards, WG and De Rienzo, A and Hassan, R and Miettinen, M and Xi, L and Raffeld, M and Uechi, LT and Li, X and Wang, R and Chen, H and Hoang, CD and Bueno, R and Schrump, DS}, title = {UHRF1 Is a Novel Druggable Epigenetic Target in Malignant Pleural Mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {16}, number = {1}, pages = {89-103}, pmid = {32927122}, issn = {1556-1380}, support = {P30 CA016042/CA/NCI NIH HHS/United States ; R01 CA120528/CA/NCI NIH HHS/United States ; ZIA BC011115/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Animals ; CCAAT-Enhancer-Binding Proteins/genetics ; Cell Line, Tumor ; Cell Proliferation ; Epigenesis, Genetic ; Gene Expression Regulation, Neoplastic ; Humans ; *Lung Neoplasms/genetics ; *Mesothelioma/drug therapy/genetics ; *Mesothelioma, Malignant ; Mice ; *Pleural Neoplasms/drug therapy/genetics ; Ubiquitin-Protein Ligases ; }, abstract = {INTRODUCTION: Ubiquitin-like with plant homeodomain and ring finger domains 1 (UHRF1) encodes a master regulator of DNA methylation that has emerged as an epigenetic driver in human cancers. To date, no studies have evaluated UHRF1 expression in malignant pleural mesothelioma (MPM). This study was undertaken to explore the therapeutic potential of targeting UHRF1 in MPM.

METHODS: Microarray, real-time quantitative reverse transcription-polymerase chain reaction, immunoblot, and immunohistochemistry techniques were used to evaluate UHRF1 expression in normal mesothelial cells (NMCs) cultured with or without asbestos, MPM lines, normal pleura, and primary MPM specimens. The impact of UHRF1 expression on MPM patient survival was evaluated using two independent databases. RNA-sequencing, proliferation, invasion, and colony formation assays, and murine xenograft experiments were performed to evaluate gene expression and growth of MPM cells after biochemical or pharmacologic inhibition of UHRF1 expression.

RESULTS: UHRF1 expression was significantly higher in MPM lines and specimens relative to NMC and normal pleura. Asbestos induced UHRF1 expression in NMC. The overexpression of UHRF1 was associated with decreased overall survival in patients with MPM. UHRF1 knockdown reversed genomewide DNA hypomethylation, and inhibited proliferation, invasion, and clonogenicity of MPM cells, and growth of MPM xenografts. These effects were phenocopied by the repurposed chemotherapeutic agent, mithramycin. Biochemical or pharmacologic up-regulation of p53 significantly reduced UHRF1 expression in MPM cells. RNA-sequencing experiments exhibited the pleiotropic effects of UHRF1 down-regulation and identified novel, clinically relevant biomarkers of UHRF1 expression in MPM.

CONCLUSIONS: UHRF1 is an epigenetic driver in MPM. These findings support the efforts to target UHRF1 expression or activity for mesothelioma therapy.}, } @article {pmid32922794, year = {2020}, author = {Tada, Y and Tagawa, M and Yusa, T and Yatomi, M and Shimomura, I and Suzuki, T and Takeshita, Y and Sato, T and Shimada, H and Hiroshima, K}, title = {Diffuse pleural thickening and thoracic contraction: An indistinguishable case from malignant pleural mesothelioma.}, journal = {SAGE open medical case reports}, volume = {8}, number = {}, pages = {2050313X20948716}, pmid = {32922794}, issn = {2050-313X}, abstract = {The differential diagnosis of reactive mesothelial hyperplasia and mesothelioma is difficult. We present a rare case of diffuse pleural thickening with thoracic contraction that was indistinguishable from mesothelioma. A 66-year-old woman with no history of asbestos exposure visited our hospital with a complaint of dyspnea. The clinical findings included circumferential pleural thickening on chest computed tomography image and a high concentration of hyaluronic acid in the pleural fluid. Pleural biopsies obtained by thoracoscopy under local anesthesia were pathologically consistent with mesothelioma, but the patient refused to take any kind of mesothelioma treatments. Four months later, she consented to a surgical pleural biopsy under general anesthesia to obtain larger tissue samples, which included typical proliferating polygonal cells positive for CAM5.2, calretinin, WT-1, D2-40, CK5/6, epithelial membrane antigen, and glucose transporter-1 and negative for carcinoembryonic antigen, BerEP4, and MOC31. The analysis was consistent with diagnosis of epithelioid mesothelioma. Fluorescence in situ hybridization, however, showed the presence of p16 gene, and the expression of BRCA1-associated protein-1 was detected by immunohistochemistry. Our final diagnosis was diffuse pleural thickening unrelated to asbestos exposure. Differential diagnosis of diffuse pleural thickening and malignant mesothelioma is thus difficult and routine immunohistochemical examinations are often insufficient for accurate diagnosis. Multiple diagnostic methods are required for correct diagnosis in a clinically marginal case.}, } @article {pmid32911426, year = {2020}, author = {Lam, SK and Yan, S and Xu, S and Ho, JC}, title = {Targeting polyamine as a novel therapy in xenograft models of malignant pleural mesothelioma.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {148}, number = {}, pages = {138-148}, doi = {10.1016/j.lungcan.2020.08.016}, pmid = {32911426}, issn = {1872-8332}, mesh = {Animals ; Eflornithine ; Heterografts ; *Lung Neoplasms/drug therapy ; *Mesothelioma, Malignant ; Mice ; Mice, Nude ; Polyamines ; }, abstract = {INTRODUCTION: Inhalation of asbestos fibers is the key culprit in malignant pleural mesothelioma (MPM). Although the import and use of asbestos have been restricted, the incidence of MPM continues to increase globally due to the prolonged lag time in malignant transformation. The development of a novel adjuvant therapy for the minority of individuals with resectable early-stage disease and effective treatment for those with unresectable MPM are urgently needed. Our preliminary data revealed that ornithine decarboxylase (ODC) is highly expressed in MPM xenografts. This study aimed to determine the treatment effects of α-difluoromethylornithine (DFMO), a specific ODC inhibitor, in MPM xenografts.

RESULTS: In an "extended adjuvant DFMO treatment" setting, nude mice were fed with DFMO for 7 days prior to inoculation of 200,000 cells. DFMO suppressed tumor growth and increased median survival in both xenografts. In H226 xenograft, 43 % of treated mice had not reached the humane endpoint by day 132, mimicking long-term survival. DFMO decreased spermidine, increased nitrotyrosine and activated apoptosis in both xenografts. Furthermore, increase in nitrosocysteine, intratumoral IL-6, keratinocyte chemoattractant and TNFα, DNA lesion and inhibition of the Akt/mTOR pathway were induced by DFMO in H226 xenograft. In "DFMO treatment" setting, 10[7] cells were inoculated into nude mice and DFMO treatment commenced when tumor size reached ∼50-100 mm[3]. DFMO also suppressed tumor growth by similar mechanisms. Supplementation with spermidine reversed the therapeutic effect of DFMO. DFMO increased actin nitration at tyrosine 53 and inhibited actin polymerization.

CONCLUSION: DFMO is preclinically effective in treating MPM.}, } @article {pmid32892058, year = {2020}, author = {Fuso Nerini, I and Roca, E and Mannarino, L and Grosso, F and Frapolli, R and D'Incalci, M}, title = {Is DNA repair a potential target for effective therapies against malignant mesothelioma?.}, journal = {Cancer treatment reviews}, volume = {90}, number = {}, pages = {102101}, doi = {10.1016/j.ctrv.2020.102101}, pmid = {32892058}, issn = {1532-1967}, mesh = {Animals ; Antineoplastic Combined Chemotherapy Protocols/pharmacology/therapeutic use ; Clinical Trials, Phase II as Topic ; DNA Damage ; *DNA Repair ; Humans ; Mesothelioma, Malignant/*drug therapy/*genetics ; Mutation ; Poly(ADP-ribose) Polymerase Inhibitors/administration & dosage/*pharmacology/therapeutic use ; Randomized Controlled Trials as Topic ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare malignancy mainly caused by asbestos exposure. Germinal and acquired mutations in genes of DNA repair pathways, in particular of homologous recombination repair, are frequent in MPM. Here we overview the available experimental data suggesting that an impaired DNA repair system affects MPM pathogenesis by leaving lesions through the genome unresolved. DNA repair defects represent a vulnerability of MPM, and it seems plausible to propose that leveraging these deficiencies could have therapeutic potential for patients with MPM, for whom there is an urgent need of more effective therapies.}, } @article {pmid32888937, year = {2020}, author = {Prabhakaran, S and Hocking, A and Kim, C and Hussey, M and Klebe, S}, title = {The potential utility of GATA binding protein 3 for diagnosis of malignant pleural mesotheliomas.}, journal = {Human pathology}, volume = {105}, number = {}, pages = {1-8}, doi = {10.1016/j.humpath.2020.08.005}, pmid = {32888937}, issn = {1532-8392}, mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Female ; GATA3 Transcription Factor/*analysis ; Humans ; *Immunohistochemistry ; Ki-67 Antigen/analysis ; Male ; Mesothelioma, Malignant/*chemistry/mortality/pathology/therapy ; Middle Aged ; Pleural Neoplasms/*chemistry/mortality/pathology/therapy ; Predictive Value of Tests ; Prognosis ; Tumor Suppressor Proteins/analysis ; Ubiquitin Thiolesterase/analysis ; }, abstract = {Malignant pleural mesothelioma is associated with asbestos exposure and poor outcomes. The usefulness of immunohistochemistry for diagnosis of sarcomatoid mesothelioma, especially the desmoplastic type, is limited, and more effective markers are required. GATA binding protein 3 (GATA3) has been suggested as a diagnostic marker for sarcomatoid mesothelioma. The potential usefulness of GATA3 for prognostication and its clinical and pathological correlations in different subtypes of mesothelioma have not been evaluated. We investigated the immunohistochemical labeling and associations for GATA3, BRCA1-associated protein 1 (BAP1), and Ki67 labeling in three major histological types of pleural malignant mesotheliomas. We examined 149 clinically annotated malignant mesotheliomas and assessed associations of GATA3 expression with clinical variables and prognosis. In addition, we labeled 10 cases of fibrous pleuritis with GATA3, all of which were negative. GATA3 was positive in 75 of 149 (50%) mesotheliomas, with the highest incidence of labeling seen in the sarcomatoid subtype (73%), compared with the biphasic (50%) and epithelioid (40%), mesotheliomas. A total of eight desmoplastic mesotheliomas showed labeling with GATA3. Patients whose tumors had sarcomatoid histology showed poorer survival than those with the other subtypes (p < 0.001), but overall GATA3 labeling did not have a statistically significant association with survival (p = 0.602). There was no association of GATA3 labeling and BAP1 status or Ki67 index. Our study includes the largest cohort of mesotheliomas that has been labeled for GATA3 to date. GATA3 is a useful marker for sarcomatoid mesothelioma, including the desmoplastic subtype. Discordance in GATA3 and BAP1 labeling of epithelioid and sarcomatoid components in the biphasic subtype is not uncommon.}, } @article {pmid32888453, year = {2020}, author = {Nowak, AK and Lesterhuis, WJ and Kok, PS and Brown, C and Hughes, BG and Karikios, DJ and John, T and Kao, SC and Leslie, C and Cook, AM and Pavlakis, N and Briscoe, K and O'Byrne, KJ and Karapetis, CS and Lam, WS and Langford, A and Yip, S and Stockler, MR}, title = {Durvalumab with first-line chemotherapy in previously untreated malignant pleural mesothelioma (DREAM): a multicentre, single-arm, phase 2 trial with a safety run-in.}, journal = {The Lancet. Oncology}, volume = {21}, number = {9}, pages = {1213-1223}, doi = {10.1016/S1470-2045(20)30462-9}, pmid = {32888453}, issn = {1474-5488}, mesh = {Adolescent ; Adult ; Aged ; Antibodies, Anti-Idiotypic/administration & dosage/adverse effects ; Antibodies, Monoclonal/*administration & dosage/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage/adverse effects ; Australia/epidemiology ; B7-H1 Antigen/antagonists & inhibitors/genetics ; Cisplatin/*administration & dosage/adverse effects ; Female ; Humans ; Lung Neoplasms/*drug therapy/genetics/immunology/pathology ; Male ; Mesothelioma/*drug therapy/genetics/immunology/pathology ; Mesothelioma, Malignant ; Middle Aged ; Pemetrexed/*administration & dosage/adverse effects ; Pleural Neoplasms/*drug therapy/genetics/immunology/pathology ; Progression-Free Survival ; }, abstract = {BACKGROUND: There is a strong unmet need to improve systemic therapy in mesothelioma. Chemotherapy with cisplatin and pemetrexed improves survival in malignant pleural mesothelioma, and immune checkpoint inhibitors are an emerging treatment in this disease. We aimed to evaluate the activity of durvalumab, an anti-PD-L1 antibody, given during and after first-line chemotherapy with cisplatin and pemetrexed in patients with advanced malignant pleural mesothelioma.

METHODS: DREAM was a multicentre, single-arm, open-label, phase 2 trial done in nine hospitals in Australia. Eligible patients were aged 18 years or older and had histologically confirmed malignant pleural mesothelioma considered unsuitable for cancer-directed surgery, an Eastern Cooperative Oncology Group performance status of 0 or 1, and measurable disease as per the modified Response Evaluation Criteria in Solid Tumors version 1.0 (mRECIST) for mesothelioma that was previously untreated with systemic therapy. All histological subtypes were eligible. The first six participants were treated for two cycles in a safety run-in. All participants received cisplatin 75 mg/m[2], pemetrexed 500 mg/m[2], and durvalumab 1125 mg intravenously on day 1 of a 3-weekly schedule for a maximum of six cycles. Change from cisplatin to carboplatin with an area under the curve of 5 was permitted. Durvalumab was continued for a maximum of 12 months. The primary endpoint was progression-free survival at 6 months, measured according to mRECIST for malignant pleural mesothelioma and analysed in the intention-to-treat population. Safety analyses included all participants who receive at least one dose of any study drug. This study is registered with the Australia New Zealand Clinical Trials Registry, ACTRN12616001170415.

FINDINGS: Between Dec 28, 2016, and Sept 27, 2017, 55 participants were enrolled. 54 patients were eligible and were followed up for a median of 28·2 months (IQR 26·5-30·2). 31 (57%; 95% CI 44-70) of 54 patients were alive and progression-free at 6 months. The most common grade 3-4 adverse events were neutropenia (seven [13%] patients), nausea (six [11%]), and anaemia (four [7%]). A total of 60 serious adverse events occurred in 29 participants, five of which were considered possibly related to durvalumab. Five patients died during the study treatment; none of these five deaths were attributed to study treatment.

INTERPRETATION: The combination of durvalumab, cisplatin, and pemetrexed has promising activity and an acceptable safety profile that warrants further investigation in a randomised phase 3 trial.

FUNDING: AstraZeneca.}, } @article {pmid32887638, year = {2020}, author = {Dell'Anno, I and Barone, E and Mutti, L and Rassl, DM and Marciniak, SJ and Silvestri, R and Landi, S and Gemignani, F}, title = {Tissue expression of lactate transporters (MCT1 and MCT4) and prognosis of malignant pleural mesothelioma (brief report).}, journal = {Journal of translational medicine}, volume = {18}, number = {1}, pages = {341}, pmid = {32887638}, issn = {1479-5876}, support = {G0601840/MRC_/Medical Research Council/United Kingdom ; G1002610/MRC_/Medical Research Council/United Kingdom ; MR/R009120/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Basigin/metabolism ; Humans ; *Mesothelioma, Malignant ; Monocarboxylic Acid Transporters ; Muscle Proteins/metabolism ; Prognosis ; *Symporters ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive neoplasm of the pleura, mainly related to asbestos exposure. As in other solid tumors, malignant cells exhibit high glucose uptake and glycolytic rates with increased lactic acid efflux into the interstitial space. Lactate transport into and out of cells, crucial to maintaining intracellular pH homeostasis and glycolysis, is carried out by monocarboxylate transporters (MCTs) and the chaperone basigin (CD147). We set out to examine the clinical significance of basigin, MCT1 and MCT4 in the context of MPM and to evaluate their expression in relation to the evolution of the disease.

METHODS: We used immunohistochemistry to measure the expression of basigin, MCT1 and MCT4 in a cohort of 135 individuals with MPM compared to a series of 15 non-MPM pleura specimens. Moreover, by Kaplan-Meier and Cox analyses we evaluated whether an expression over the average of these markers could be associated with the patients' overall survival (OS).

RESULTS: We detected positive staining of basigin, MCT1, and MCT4 in most MPM specimens. In particular, MCT4 was always positive in malignant tissues but undetectable in the 4 normal pleural specimens incorporated within the tissue microarray. This was confirmed in the additional series of 15 normal pleural samples. Moreover, MCT4 expression was significantly associated with reduced OS.

CONCLUSION: In this study, the tissue expression of basigin did not prove to be exploitable as a diagnostic or prognostic marker for MPM patients. The expression of MCT1 was not informative either, being tightly correlated with that of basigin. However, the expression of MCT4 showed promise as a diagnostic/therapeutic and prognostic biomarker.}, } @article {pmid32882916, year = {2020}, author = {Cakiroglu, E and Senturk, S}, title = {Genomics and Functional Genomics of Malignant Pleural Mesothelioma.}, journal = {International journal of molecular sciences}, volume = {21}, number = {17}, pages = {}, pmid = {32882916}, issn = {1422-0067}, mesh = {Animals ; Biomarkers, Tumor/genetics/*metabolism ; Genomics/*methods ; Humans ; Mesothelioma, Malignant/genetics/metabolism/*pathology ; Phenomics/*methods ; Pleural Neoplasms/genetics/metabolism/*pathology ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer of the mesothelial cells lining the pleural surface of the chest wall and lung. The etiology of MPM is strongly associated with prior exposure to asbestos fibers, and the median survival rate of the diagnosed patients is approximately one year. Despite the latest advancements in surgical techniques and systemic therapies, currently available treatment modalities of MPM fail to provide long-term survival. The increasing incidence of MPM highlights the need for finding effective treatments. Targeted therapies offer personalized treatments in many cancers. However, targeted therapy in MPM is not recommended by clinical guidelines mainly because of poor target definition. A better understanding of the molecular and cellular mechanisms and the predictors of poor clinical outcomes of MPM is required to identify novel targets and develop precise and effective treatments. Recent advances in the genomics and functional genomics fields have provided groundbreaking insights into the genomic and molecular profiles of MPM and enabled the functional characterization of the genetic alterations. This review provides a comprehensive overview of the relevant literature and highlights the potential of state-of-the-art genomics and functional genomics research to facilitate the development of novel diagnostics and therapeutic modalities in MPM.}, } @article {pmid32881200, year = {2020}, author = {Mori, D and Kido, S and Hiraki, M and Sumi, K and Ureshino, N and Masuda, M and Nabeshima, K and Akashi, M}, title = {Peritoneal adenomatoid (microcystic) mesothelioma.}, journal = {Pathology international}, volume = {70}, number = {11}, pages = {876-880}, doi = {10.1111/pin.13006}, pmid = {32881200}, issn = {1440-1827}, mesh = {Adenomatoid Tumor/*pathology ; Female ; Humans ; In Situ Hybridization, Fluorescence/methods ; Mesothelioma/*pathology ; Mesothelioma, Malignant/diagnosis/pathology ; Middle Aged ; Peritoneal Neoplasms/diagnosis/*pathology ; Peritoneum/*pathology ; Prognosis ; }, abstract = {There are several reports of pleural adenomatoid (microcystic) mesothelioma, but peritoneal adenomatoid mesothelioma is extremely rare. A 64-year-old Japanese woman presented with no symptoms and no asbestos exposure history. An abdominal computed tomography scan revealed multiple hypervascular masses on the liver surface, pelvic cavity and anterior peritoneum. Over 10 pieces of the multiple resected tumors showed numerous microcysts composed of a bland mesothelial cell background with rich capillary vessels. Focally, atypical cells with bizarre nuclei with prominent nucleoli were observed. Adenomatoid mesothelioma was suspected based on histochemical, immunohistochemical and fluorescence in situ hybridization findings. The tumors relapsed 4 years later and metastasized to the lung, but the patient remains alive 7 years after the first tumor resection surgery. Although the prognosis of adenomatoid mesothelioma of pleural origin is poor, the progression of this peritoneal case is slow.}, } @article {pmid32875620, year = {2020}, author = {Petrof, O and Neyens, T and Nuyts, V and Nackaerts, K and Nemery, B and Faes, C}, title = {On the impact of residential history in the spatial analysis of diseases with a long latency period: A study of mesothelioma in Belgium.}, journal = {Statistics in medicine}, volume = {39}, number = {26}, pages = {3840-3866}, doi = {10.1002/sim.8697}, pmid = {32875620}, issn = {1097-0258}, mesh = {*Asbestos/toxicity ; Belgium/epidemiology ; Humans ; *Lung Neoplasms/epidemiology/etiology ; *Mesothelioma/epidemiology/etiology ; *Mesothelioma, Malignant ; *Occupational Exposure ; Spatial Analysis ; }, abstract = {Mesothelioma is a rare cancer caused by exposure to asbestos. Belgium has a known long history of asbestos production, resulting in one of the highest mesothelioma mortality rates worldwide. While the production of asbestos has stopped completely, the long latency period of mesothelioma, which can fluctuate between 20 and 40 years after exposure, causes incidences still to be frequent. Mesothelioma's long incubation time affects our assessment of its geographical distribution as well. Since patients' residential locations are likely to change a number of times throughout their lives, the location where the patients develop the disease is often far from the location where they were exposed to asbestos. Using the residential history of patients, we propose the use of a convolution multiple membership model (MMM), which includes both a spatial conditional autoregressive and an unstructured random effect. Pancreatic cancer patients are used as a control population, reflecting the population at risk for mesothelioma. Results show the impact of the residential mobility on the geographical risk estimation, as well as the importance of acknowledging the latency period of a disease. A simulation study was conducted to investigate the properties of the convolution MMM. The robustness of the results for the convolution MMM is assessed via a sensitivity analysis.}, } @article {pmid32869268, year = {2020}, author = {Sayan, M and Mamidanna, S and Fuat Eren, M and Daliparty, V and Zoto Mustafayev, T and Nelson, C and Ohri, N and Jabbour, SK and Guven Mert, A and Atalar, B}, title = {New horizons from novel therapies in malignant pleural mesothelioma.}, journal = {Advances in respiratory medicine}, volume = {88}, number = {4}, pages = {343-351}, pmid = {32869268}, issn = {2543-6031}, support = {R50 CA275877/CA/NCI NIH HHS/United States ; }, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Asbestos/*adverse effects ; Clinical Trials as Topic ; Humans ; Mesothelioma, Malignant/chemically induced/*therapy ; Neoplasm Staging ; Pleural Neoplasms/chemically induced/*therapy ; Radiotherapy, Adjuvant ; }, abstract = {Malignant pleural mesothelioma (MPM) is a relatively rare, but highly lethal cancer of the pleural mesothelial cells. Its pathoge-nesis is integrally linked to asbestos exposure. In spite of recent developments providing a more detailed understanding of the pathogenesis, the outcomes continue to be poor. To date, trimodality therapy involving surgery coupled with chemotherapy and/or radiotherapy remains the standard of therapy. The development of resistance of the tumor cells to radiation and several che-motherapeutic agents poses even greater challenges in the management of this cancer. Ionizing radiation damages cancer cell DNA and aids in therapeutic response, but it also activates cell survival signaling pathways that helps the tumor cells to overcome radiation-induced cytotoxicity. A careful evaluation of the biology involved in mesothelioma with an emphasis on the workings of pro-survival signaling pathways might offer some guidance for treatment options. This review focuses on the existing treatment options for MPM, novel treatment approaches based on recent studies combining the use of inhibitors which target different pro-survival pathways, and radiotherapy to optimize treatment.}, } @article {pmid36238033, year = {2020}, author = {Bae, JY and Kim, Y and Kang, HJ and Kwon, H and Shim, SS}, title = {Imaging Features of Various Benign and Malignant Tumors and Tumorlike Conditions of the Pleura: A Pictorial Review.}, journal = {Taehan Yongsang Uihakhoe chi}, volume = {81}, number = {5}, pages = {1109-1120}, pmid = {36238033}, issn = {2288-2928}, abstract = {Pleural masses may be caused by various conditions, including benign and malignant neoplasms and non-neoplastic tumorlike conditions. Primary pleural neoplasms include solitary fibrous tumor, malignant mesothelioma, and primary pleural non-Hodgkin's lymphoma. Metastatic disease is the most common neoplasm of the pleura and may uncommonly occur in patients with hematologic malignancy, including lymphoma, leukemia, and multiple myeloma. Pleural effusion is usually associated with pleural malignancy. Rarely, pleural malignancy may arise from chronic empyema, and the most common cell type is non-Hodgkin's lymphoma (pyothorax-associated lymphoma). Non-neoplastic pleural masses may be observed in several benign conditions, including tuberculosis, pleural plaques caused by asbestos exposure, and pleural loose body. Herein, we present a review of benign and malignant pleural neoplasms and tumorlike conditions with illustrations of their computed tomographic images.}, } @article {pmid32863225, year = {2020}, author = {Ito, F and Yanatori, I and Maeda, Y and Nimura, K and Ito, S and Hirayama, T and Nagasawa, H and Kohyama, N and Okazaki, Y and Akatsuka, S and Toyokuni, S}, title = {Asbestos conceives Fe(II)-dependent mutagenic stromal milieu through ceaseless macrophage ferroptosis and β-catenin induction in mesothelium.}, journal = {Redox biology}, volume = {36}, number = {}, pages = {101616}, pmid = {32863225}, issn = {2213-2317}, mesh = {Animals ; *Asbestos ; Epithelium ; *Ferroptosis ; Ferrous Compounds ; Hydrogen Peroxide ; Macrophages ; *Mesothelioma ; Mutagens ; Rats ; beta Catenin/genetics ; }, abstract = {Asbestos is still a social burden worldwide as a carcinogen causing malignant mesothelioma. Whereas recent studies suggest that local iron reduction is a preventive strategy against carcinogenesis, little is known regarding the cellular and molecular mechanisms surrounding excess iron. Here by differentially using high-risk and low-risk asbestos fibers (crocidolite and anthophyllite, respectively), we identified asbestos-induced mutagenic milieu for mesothelial cells. Rat and cell experiments revealed that phagocytosis of asbestos by macrophages results in their distinctive necrotic death; initially lysosome-depenent cell death and later ferroptosis, which increase intra- and extra-cellular catalytic Fe(II). DNA damage in mesothelial cells, as assessed by 8-hydroxy-2'-deoxyguanosine and γ-H2AX, increased after crocidolite exposure during regeneration accompanied by β-catenin activation. Conversely, β-catenin overexpression in mesothelial cells induced higher intracellular catalytic Fe(II) with increased G2/M cell-cycle fraction, when p16[INK4A] genomic loci localized more peripherally in the nucleus. Mesothelial cells after challenge of H2O2 under β-catenin overexpression presented low p16[INK4A] expression with a high incidence of deletion in p16[INK4A] locus. Thus, crocidolite generated catalytic Fe(II)-rich mutagenic environment for mesothelial cells by necrotizing macrophages with lysosomal cell death and ferroptosis. These results suggest novel molecular strategies to prevent mesothelial carcinogenesis after asbestos exposure.}, } @article {pmid32849853, year = {2020}, author = {Bai, Y and Wang, X and Hou, J and Geng, L and Liang, X and Ruan, Z and Guo, H and Nan, K and Jiang, L}, title = {Identification of a Five-Gene Signature for Predicting Survival in Malignant Pleural Mesothelioma Patients.}, journal = {Frontiers in genetics}, volume = {11}, number = {}, pages = {899}, pmid = {32849853}, issn = {1664-8021}, abstract = {Malignant pleural mesothelioma (MPM), predominantly caused by asbestos exposure, is a highly aggressive cancer with poor prognosis. The staging systems currently used in clinics is inadequate in evaluating the prognosis of MPM. In this study, a five-gene signature was developed and enrolled into a prognostic risk score model by LASSO Cox regression analysis based on two expression profiling datasets (GSE2549 and GSE51024) from Gene Expression Omnibus (GEO). The five-gene signature was further validated using the Cancer Genome Atlas (TCGA) MPM dataset. Univariate and multivariate Cox analyses proved that the five-gene signature was an independent prognostic factor for MPM. The signature remained statistically significant upon stratification by Brigham stage, AJCC stage, gender, tumor size, and lymph node status. Time-dependent receiver operating characteristic (ROC) curve indicated good performance of our model in predicting 1- and 2-years overall survival in MPM patients. The C-index was 0.784 for GSE2549 and 0.753 for the TCGA dataset showing moderate predictive accuracy of our model. Furthermore, Gene Set Enrichment Analysis suggested that the five-gene signature was related to pathways resulting in MPM tumor progression. Together, we have established a five-gene signature significantly associated with prognosis in MPM patients. Hence, the five-genes signature may serve as a potentially useful prognostic tool for MPM patients.}, } @article {pmid32847019, year = {2020}, author = {Airoldi, C and Ferrante, D and Mirabelli, D and Azzolina, D and Magnani, C}, title = {Evaluation of Nonresponse Bias in a Case-Control Study of Pleural Mesothelioma.}, journal = {International journal of environmental research and public health}, volume = {17}, number = {17}, pages = {}, pmid = {32847019}, issn = {1660-4601}, mesh = {Aged ; Aged, 80 and over ; *Asbestos ; Bias ; Case-Control Studies ; Female ; Humans ; Male ; *Mesothelioma ; Middle Aged ; *Occupational Exposure ; *Pleural Neoplasms ; }, abstract = {Nonparticipation limits the power of epidemiological studies, and can cause bias. In a case-control study on pleural malignant mesothelioma (MM), we found low participation in interviews (63%) among controls. Our goal was to characterize nonresponder controls and assess nonresponse bias in our study. We selected all nonresponder controls (204) and a random sample of responder controls (174). Data were obtained linking hospital admissions and town registrars, and concordance between sources was assessed. Nonresponse bias was evaluated using a logistic regression model applying the inverse probability weighting approach. The odds ratio (OR) for the status of the respondents was 0.61 (95% confidence interval (CI): 0.33-1.16) for controls aged 61-70, 0.37 (CI: 0.20-0.66) for those aged 71-80, and 0.40 (CI: 0.20-0.80) for those aged above 80 (reference group: ≤60 years). Controls with low education level had lower OR (0.47; CI: 0.26-0.84). After adjustment, the ORs for MM by categories of cumulative exposure to asbestos were similar to the unadjusted results, ranging from 4.6 (CI: 1.8-11.7) for cumulative exposures between 0.1 and 1 f/mL-y to 57.5 (CI: 20.2-163.9) above 10 f/mL-y. Responder controls were younger and had higher education level. Nevertheless, there was little evidence of bias from nonresponse in the risk estimates of MM.}, } @article {pmid32826527, year = {2021}, author = {Mujahed, T and Tazelaar, HD and Sukov, WR and Halling, KC and Davila, JI and Glass, C and Pavlisko, EN and Strickland, KC and Roggli, V and Haque, M and Mneimneh, W and Carter, E and Galateau-Salle, F and Glidden, D and Garcia-Kennedy, R and Larsen, BT}, title = {Malignant Peritoneal Mesothelioma Arising in Young Adults With Long-standing Indwelling Intra-abdominal Shunt Catheters.}, journal = {The American journal of surgical pathology}, volume = {45}, number = {2}, pages = {255-262}, doi = {10.1097/PAS.0000000000001574}, pmid = {32826527}, issn = {1532-0979}, mesh = {Adolescent ; Adult ; Catheters, Indwelling/*adverse effects ; Female ; Humans ; Male ; Mesothelioma, Malignant/*etiology/pathology ; Middle Aged ; Peritoneal Neoplasms/*etiology/pathology ; Portasystemic Shunt, Surgical/*adverse effects ; Ventriculoperitoneal Shunt/*adverse effects ; Young Adult ; }, abstract = {Only 50% to 70% of patients with mesothelioma report asbestos exposure. Other exposures (eg, radiation) play a role in some cases, but some patients have no obvious cause. We describe a series of patients with long-standing indwelling intra-abdominal shunt catheters who developed malignant peritoneal mesothelioma, suggesting a novel association. We identified 7 patients who had shunts and subsequently developed mesothelioma (5 women; median age: 31 y, range: 18 to 45 y). Clinical history and pathology materials were reviewed, and RNA sequencing was performed. Clinical presentations varied; 6 patients had hydrocephalus and a ventriculoperitoneal shunt, and 1 patient had portal hypertension and a portoatrial shunt. The median duration of shunt therapy in 5 cases was 29 years (range: 12 to 35 y); the remaining 2 patients also had shunts for many years, but specific details were unavailable. Two patients had radiotherapy for malignancies in childhood. One had an alleged exposure to asbestos and 1 had prior exposure to talc. The rest had no known risk factors. Histologically, all tumors were purely epithelioid. Treatments included surgical debulking, chemotherapy, and palliative care. All 7 died of disease (median survival: 7 mo, range: 1 to 18 mo). Molecular testing showed loss of NF2 and CDKN2A/B and a BAP1 mutation in 1 case, and no genomic alterations associated with mesothelioma in 2 cases. Peritoneal mesothelioma may represent a complication of long-standing indwelling shunt catheters. The mechanism is unknown, but chronic peritoneal irritation may play a role. Albeit rare, mesothelioma should be considered in patients with a shunt who present with new ascites.}, } @article {pmid32823952, year = {2020}, author = {Johnson, TG and Schelch, K and Lai, K and Marzec, KA and Kennerson, M and Grusch, M and Reid, G and Burgess, A}, title = {YB-1 Knockdown Inhibits the Proliferation of Mesothelioma Cells through Multiple Mechanisms.}, journal = {Cancers}, volume = {12}, number = {8}, pages = {}, pmid = {32823952}, issn = {2072-6694}, support = {IIRS-18-103//National Breast Cancer Foundation/ ; T 1062 Firnberg Program//Austrian Science Fund/ ; }, abstract = {Y-box binding protein-1 (YB-1) is a multifunctional oncoprotein that has been shown to regulate proliferation, invasion and metastasis in a variety of cancer types. We previously demonstrated that YB-1 is overexpressed in mesothelioma cells and its knockdown significantly reduces tumour cell proliferation, migration, and invasion. However, the mechanisms driving these effects are unclear. Here, we utilised an unbiased RNA-seq approach to characterise the changes to gene expression caused by loss of YB-1 knockdown in three mesothelioma cell lines (MSTO-211H, VMC23 and REN cells). Bioinformatic analysis showed that YB-1 knockdown regulated 150 common genes that were enriched for regulators of mitosis, integrins and extracellular matrix organisation. However, each cell line also displayed unique gene expression signatures, that were differentially enriched for cell death or cell cycle control. Interestingly, deregulation of STAT3 and p53-pathways were a key differential between each cell line. Using flow cytometry, apoptosis assays and single-cell time-lapse imaging, we confirmed that MSTO-211H, VMC23 and REN cells underwent either increased cell death, G1 arrest or aberrant mitotic division, respectively. In conclusion, this data indicates that YB-1 knockdown affects a core set of genes in mesothelioma cells. Loss of YB-1 causes a cascade of events that leads to reduced mesothelioma proliferation, dependent on the underlying functionality of the STAT3/p53-pathways and the genetic landscape of the cell.}, } @article {pmid32823056, year = {2020}, author = {Torres-Roman, JS and Gomez-Rubio, V and Sanchez-Trujillo, L and Delgado-Rosas, E and Puche-Vergara, F and Sanz-Anquela, JM and Ortega, MA}, title = {Geographic study of mortality due to mesothelioma in Peru and its evolution.}, journal = {Cancer epidemiology}, volume = {68}, number = {}, pages = {101791}, doi = {10.1016/j.canep.2020.101791}, pmid = {32823056}, issn = {1877-783X}, mesh = {Adolescent ; Adult ; Asbestos/*adverse effects ; Carcinogens/*toxicity ; Child ; Child, Preschool ; Female ; Geography ; Humans ; Infant ; Infant, Newborn ; Male ; Mesothelioma/epidemiology/etiology/*mortality ; Middle Aged ; Occupational Exposure/*adverse effects ; Peru/epidemiology ; Prognosis ; Survival Rate ; Young Adult ; }, abstract = {BACKGROUND: Peru has a public health problem because of asbestos imports. We analyzed the mortality trends for mesothelioma in Peru and its provinces from 2005 to 2014 and estimated their relationship with the amount of asbestos imported previously.

METHODS: We computed age-standardized mortality rates (ASMRs) per 100,000 population (direct method and SEGI world standard population reference), and the standardized mortality ratio (SMR). The relationship between the amount of asbestos imported annually along the period 1965-2010 and the number of mesothelioma deaths per year from 2005 to 2014 was estimated by log-linear Poisson regression models and Pearson correlation calculations.

RESULTS: After correcting the number of deaths, Peru registered 428 cases (or 430 when corrected cases are rounded by sex) between 2005 and 2014. The highest ASMRs were in Arequipa and Callao (range: 0.40-0.41/100,000 population), followed by Huancavelica (0.36/100,000 population). This translates into approximately one death per each 68-111 of asbestos tons imported. The latency period for the higher level of positive correlation found was 8 years (r = 0.8). Male female sex ratio was lower in provinces such as Junin and Hunacavelica with geological asbestos risk.

CONCLUSIONS: Two patterns of mesothelioma risk have been detected, occupational and environmental. During the 2002-2006 years, Peru increased the asbestos use. If crocidolite imports were also increased, this could be behind the 8 years latency period detected. Peru should boost strategies towards the total ban of all forms of asbestos.}, } @article {pmid32816595, year = {2021}, author = {Johnson, NF}, title = {Inhalation Toxicity of Talc.}, journal = {Journal of aerosol medicine and pulmonary drug delivery}, volume = {34}, number = {2}, pages = {79-107}, doi = {10.1089/jamp.2020.1609}, pmid = {32816595}, issn = {1941-2703}, mesh = {Administration, Inhalation ; Animals ; Carcinogens ; Humans ; Lung ; *Lung Neoplasms ; *Talc/toxicity ; }, abstract = {Respirable talc powder (RTP) is a complex mineral mixture of talc along with accessory minerals, including tremolite, anthophyllite, quartz, magnesite, dolomite, antigorite, lizardite, and chlorite. The industrial mining, milling, and processing of talc ore is associated with elevated incidences of fibrotic and neoplastic diseases, which are also seen among workers exposed to RTP in secondary industries and individuals using processed cosmetic talc for personal use. There is controversial evidence of a link between the talc-induced lung diseases and a potential contamination with asbestos fibers. This controversy is fueled by inadequate exposure data and the complex mineralogy and terminology of the accessory minerals. Talc aerosols exhibit a wide range of mineral habits, including particulates and fibrous structures that have dimensional and compositional characteristics related to the development of asbestos-related lung disease. The inhalation toxicology of RTP is based on the analysis of occupational hygiene and animal inhalation studies conducted between the 1940s and the 1990s and more recent mechanistic studies conducted both in vivo and in vitro. The review of talc toxicity studies reveals that the occupational studies provide only equivocal links between any of the components of the aerosols and the development of pulmonary cancer; however, there is substantial evidence of an association between the aerosols and pleural and pulmonary fibrosis and the development of nonmalignant respiratory disease. The animal inhalation and implantation studies appear to be less than optimal, which also appears to be true for the in vivo and in vitro studies. The mechanistic studies have identified the key pathogenic characteristics of asbestos to be long and thin fibers that are durable in lung tissues and fluids. Talc toxicity studies show that talc particles and fibers are durable and can remain in the lung for up to 40 years after the end of exposure. This extended tissue residence is considered to constitute a continuing tissue exposure that is capable of inducing the documented inflammatory and proliferative response. There is less consensus as to whether there is a threshold fiber length effect, as long, thin fibers (>5 μm) form only a small fraction of talc aerosols and the possible role of fibers >5 μm in the translocation from the lung to the pleura and their association with pleural fibrotic and carcinogenic lesions. Long, thin fibers are preferentially deposited in hot spots in the lung, such as airway bifurcations, areas typically associated with the development of lung cancer. The platy structures typical of talc can form oblate structures behaving more as fibers in the air stream, and these have also been shown to deposit preferentially in such locations. The review of the inhalation toxicity of talc provides a plausible explanation for the carcinogenic potential of RTP.}, } @article {pmid32815857, year = {2020}, author = {Alpert, N and van Gerwen, M and Flores, R and Taioli, E}, title = {Gender Differences in Outcomes of Patients With Mesothelioma.}, journal = {American journal of clinical oncology}, volume = {43}, number = {11}, pages = {792-797}, pmid = {32815857}, issn = {1537-453X}, support = {P30 CA196521/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Mesothelioma, Malignant/*mortality ; Middle Aged ; Pleural Neoplasms/*mortality ; *Sex Characteristics ; Survival Rate ; Treatment Outcome ; United Kingdom/epidemiology ; }, abstract = {BACKGROUND: Mesothelioma is a rare and deadly form of cancer, linked to asbestos exposure. Although the United Kingdom has banned asbestos, the incidence rate remains high. Previous research has indicated that female individuals have better survival than male individuals, but this has never been examined in the United Kingdom.

MATERIALS AND METHODS: Pleural mesothelioma cases from 2005 to 2014 were extracted from the United Kingdom Lung Cancer Dataset. Multivariable logistic regression was used to assess the clinical and demographic factors associated with gender. A multivariable Cox proportional hazards model and propensity matching methods were used to assess gender differences in overall survival while accounting for potential confounders.

RESULTS: There were 8479 (87.8%) male and 1765 (17.2%) female individuals included in the analysis. Female individuals were significantly younger, with more epithelial histology than male individuals. Female individuals had significantly better overall survival (adjusted hazard ratio, 0.85, 95% confidence interval, 0.81-0.90). Results remained similar when stratifying by age and performance status, and when limiting to patients with epithelial histology.

CONCLUSIONS: The study increases knowledge about gender differences in mesothelioma survival and is the first to directly examine this in the United Kingdom. It further disentangles the effects of age, histology, and health status. Increased estrogen may improve survival and could provide a potential target for future therapies.}, } @article {pmid32811344, year = {2021}, author = {Barbieri, PG and Mirabelli, D}, title = {Diagnosis of lung cancer: a necropsy-based study of 128 cases (1997-2016).}, journal = {Tumori}, volume = {107}, number = {3}, pages = {226-230}, doi = {10.1177/0300891620949665}, pmid = {32811344}, issn = {2038-2529}, mesh = {Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Asbestosis/diagnosis ; Autopsy/methods ; Female ; Humans ; Lung Neoplasms/chemically induced/*diagnosis ; Male ; Mesothelioma/chemically induced/diagnosis ; Mesothelioma, Malignant/chemically induced/diagnosis ; Middle Aged ; Pleural Diseases/chemically induced/diagnosis ; Pleural Neoplasms/chemically induced/diagnosis ; Prevalence ; }, abstract = {BACKGROUND: The diagnosis of lung cancer (LC) may be difficult to make in the elderly. We report on the diagnostic elements available in life in an LC necropsy case series of asbestos-exposed workers and describe the frequency of non-neoplastic asbestos-related diseases as biological exposure indices.

METHODS: We reviewed pathologic and clinical records of an unselected series of autopsies (1997-2016) in patients with LC employed in the Monfalcone shipyards. We assessed the consistency with autopsy results of diagnoses based on, respectively, radiologic, cytologic, and histologic findings.

RESULTS: Data on 128 autopsy-confirmed LC cases were available; in life, 119 had been diagnosed as LC. Among these, 49 had histologic confirmation of diagnosis (17 with immunophenotyping); histology had been negative in 4. Cytology had been the main positive finding and the basis for diagnosis in 24 cases, but had been negative in 13. Chest computed tomography had been the basis for diagnosis in 45; in 18 cases, it had been negative. Nine patients had received a diagnosis different from LC, among whom 4 had been suspected to have malignant pleural mesothelioma by chest computed tomography. Pleural plaques were found in 124 and histologic asbestosis in 46 cases.

CONCLUSIONS: Autopsies confirmed all LC diagnoses received in life, including 46 that would have been considered only possible LC based on clinical workup. The overall survival in this case series was poor. The high prevalence of pleural plaques and asbestosis suggest severity of asbestos exposures.}, } @article {pmid32787452, year = {2020}, author = {Uhlenhopp, DJ and Saliares, A and Gaduputi, V and Sunkara, T}, title = {An Unpleasant Surprise: Abdominal Presentation of Malignant Mesothelioma.}, journal = {Journal of investigative medicine high impact case reports}, volume = {8}, number = {}, pages = {2324709620950121}, pmid = {32787452}, issn = {2324-7096}, mesh = {Abdominal Pain/etiology ; Aged ; Asbestos/*adverse effects ; Diagnosis, Differential ; Fatal Outcome ; Humans ; Immunohistochemistry ; Male ; Mesothelioma, Malignant/*chemically induced/*pathology ; Retroperitoneal Neoplasms/*chemically induced/*pathology ; }, abstract = {Malignant mesothelioma is an aggressive cancer associated with asbestos exposure with median survival time of 8 to 14 months following diagnosis. Given that mesothelial cells also line the peritoneum and pericardium, malignant mesothelioma can present in unusual sites and in patients with nonrespiratory complaints. A 73-year-old male presented to the emergency department for worsening intermittent diffuse abdominal pain for the past 3 months with associated unintentional 40-pound weight loss, early satiety, and diarrhea. He denied exposure to asbestos. Computed tomography imaging revealed multiple masses concerning for malignancy including the primary retroperitoneal mass, a mass involving the terminal ileum, and a mass in the right upper lung. Esophagogastroduodenoscopy demonstrated significant mass effect within the stomach without signs of endoluminal infiltration. Computed tomography-guided biopsy of the retroperitoneal abdominal and intramuscular paraspinal masses was performed. Stage IV epithelioid mesothelioma was confirmed when hematoxylin and eosin staining revealed pleomorphic malignancy nuclei containing a vesicular chromatin pattern and prominent nucleoli and immunohistochemical staining was positive for CK Oscar, cytokeratin 7, GATA3, calretinin, EMA, and CK5/6. He was started on cisplatin, pemetrexed, and bevacizumab but developed severe abdominal pain with pneumoperitoneum and bowel perforation 1 month later and expired shortly thereafter. To our knowledge, this represents a highly atypical presentation of malignant mesothelioma considering the involvement of the retroperitoneum with diffuse lesions in the abdominopelvic cavity and thorax (sparing the lung pleurae). This case also calls attention to the occurrence of malignant mesothelioma in patients without known asbestos exposure and the crucial role of pathology in diagnosing atypical presentations.}, } @article {pmid32783735, year = {2020}, author = {Rosner, D and Markowitz, G}, title = {Baby Powders and the Precautionary Principle.}, journal = {American journal of public health}, volume = {110}, number = {9}, pages = {1378-1379}, pmid = {32783735}, issn = {1541-0048}, mesh = {Asbestos/*adverse effects ; Consumer Product Safety ; Female ; Humans ; Mesothelioma/chemically induced/prevention & control ; Ovarian Neoplasms/chemically induced/prevention & control ; Powders/adverse effects/chemistry ; Risk Factors ; Talc/*adverse effects/chemistry ; }, } @article {pmid32777272, year = {2020}, author = {Manangama, G and Gramond, C and Audignon-Durand, S and Baldi, I and Fabro-Peray, P and Gilg Soit Ilg, A and Guénel, P and Lebailly, P and Luce, D and Stücker, I and Brochard, P and Lacourt, A}, title = {Occupational exposure to unintentionally emitted nanoscale particles and risk of cancer: From lung to central nervous system - Results from three French case-control studies.}, journal = {Environmental research}, volume = {191}, number = {}, pages = {110024}, doi = {10.1016/j.envres.2020.110024}, pmid = {32777272}, issn = {1096-0953}, mesh = {Adult ; *Asbestos ; Case-Control Studies ; Central Nervous System ; Humans ; Lung ; *Lung Neoplasms/chemically induced/epidemiology ; Male ; *Occupational Diseases ; *Occupational Exposure/adverse effects ; Retrospective Studies ; }, abstract = {OBJECTIVES: Nanoscale particles (1-100 nm) can be of natural origin, and either intentionally or unintentionally produced by human activities. Toxicological data have suggested a possible carcinogenic effect of such particles. The aim of this study was to estimate the association between occupational exposure to nanoscale particles and risk of lung cancer, pleural mesothelioma and brain tumors in adults.

METHODS: Three French population-based case-control studies were analyzed: 1) the ICARE study including 2029 lung cancer cases and 2591 controls; 2) the PNSM study including 371 pleural mesothelioma cases and 730 controls and 3) the CERENAT study including 257 brain tumor cases and 511 controls. Occupational exposure to unintentionally emitted nanoscale particles (UNPs) was retrospectively assessed by a job exposure matrix providing a probability and a frequency of exposure.

RESULTS: In adjusted analyses among men, significant associations between occupational exposure to UNPs and lung cancer (OR = 1.51; 95% CI: 1.22-1.86 and brain tumors (OR = 1.69; 95% CI: 1.17-2.44) were observed. No increased OR was observed for pleural mesothelioma (OR = 0.78; 95% CI: 0.46-1.33).

CONCLUSION: This is the first study showing positive associations between occupational exposure to UNPs and increased risk of lung cancer and brain tumors. These preliminary results should encourage further epidemiological research.}, } @article {pmid32769428, year = {2021}, author = {Malpica, A and Euscher, ED and Marques-Piubelli, ML and Ferrufino-Schmidt, MC and Miranda, RN and Sams, R and Royal, RE and Raghav, KPS and Fournier, KF and Ramalingam, P}, title = {Malignant Mesothelioma of the Peritoneum in Women: A Clinicopathologic Study of 164 Cases.}, journal = {The American journal of surgical pathology}, volume = {45}, number = {1}, pages = {45-58}, doi = {10.1097/PAS.0000000000001545}, pmid = {32769428}, issn = {1532-0979}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Female ; Humans ; Mesothelioma, Malignant/mortality/*pathology/therapy ; Middle Aged ; Peritoneal Neoplasms/mortality/*pathology/therapy ; Young Adult ; }, abstract = {Malignant mesothelioma of the peritoneum in women is an uncommon tumor. In this study, we present the clinicopathologic features of 164 such cases seen in our institution over a period of 42 years (1974-2016). Clinical information, pathologic findings, immunohistochemical results, and follow-up were recorded. Hematoxylin and eosin-stained slides were reviewed in all cases. Patients ranged in age from 3 to 85 years, median: 49 years. Most patients presented with abdominal/pelvic pain, although some were asymptomatic, presented with paraneoplastic syndromes or cervical lymphadenopathy. Overall, 9% of patients had a history of direct or indirect exposure to asbestos. In total, 31% and 69% of patients had either a personal or family history of other tumors; most of these tumors are currently recognized as part of a syndrome. Genetic testing information was available in 5 patients: BAP-1 germline mutation (1), type 2 neurofibromatosis (1), Lynch syndrome (1), McCune-Albright syndrome (1), no BAP-1 or TP53 mutation (1). Most cases had gross and microscopic features typical of malignant mesothelioma of the peritoneum in women; however, some had confounding features such as gelatinous appearance, signet ring or clear cells, and well-differentiated papillary mesothelioma-like areas. Calretinin and WT-1 were the markers more frequently expressed, and up to 23% of the cases showed PAX-8 expression. Patients' treatments predominantly included: chemotherapy, cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy. On multivariate analysis, the predominance of deciduoid cells, nuclear grade 3, and the absence of surgical treatment were associated with worse overall survival (OS). For all patients, the 3- and 5-year OS were 74.3% and 57.4%, respectively. The 3- and 5-year OS for patients treated with cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy were 88.9% and 77.8%, respectively.}, } @article {pmid32769345, year = {2020}, author = {Kazaz, IO and Teoman, AS and Mungan, S}, title = {Mesothelioma of the tunica vaginalis testis: A case report.}, journal = {Indian journal of pathology & microbiology}, volume = {63}, number = {3}, pages = {475-477}, doi = {10.4103/IJPM.IJPM_780_18}, pmid = {32769345}, issn = {0974-5130}, mesh = {Aged ; Biomarkers, Tumor ; Diagnosis, Differential ; Fatal Outcome ; Humans ; Immunohistochemistry ; Male ; Mesothelioma/diagnosis/*pathology ; Mesothelioma, Malignant ; Orchiectomy ; Testicular Hydrocele/diagnosis ; Testicular Neoplasms/*diagnosis/pathology/surgery ; Testis/*pathology/surgery ; }, abstract = {Primary mesotheliomas of the tunica vaginalis testis are very rare malignant tumors. They are generally associated with exposure to asbestos. They may manifest as hydrocele, testis tumor, inguinal hernia, or epididymitis. After differential diagnosis, treatment is primarily surgical. Adjuvant therapeutic methods for mesotheliomas of the tunica vaginalis testis, with their high mortality, are controversial. Here, we present a mesothelioma case derived from tunica vaginalis testis acting as long-term pyocele with no known asbestos exposure.}, } @article {pmid32764839, year = {2020}, author = {Wang, Q and Wang, Q and Zhao, Z and Alexander, DB and Zhao, D and Xu, J and Tsuda, H}, title = {Pleural translocation and lesions by pulmonary exposed multi-walled carbon nanotubes.}, journal = {Journal of toxicologic pathology}, volume = {33}, number = {3}, pages = {145-151}, pmid = {32764839}, issn = {0914-9198}, abstract = {Carbon nanotubes (CNTs) are recently developed tubular nanomaterials, with diameters ranging from a few nanometers to tens of nanometers, and the length reaching up to several micrometers. They can be either single-walled carbon nanotubes (SWCNTs) or multi-walled carbon nanotubes (MWCNTs). Due to their nano-scaled structure, CNTs have a unique set of mechanical, electrical, and chemical properties that make them useful in information technologies, optoelectronics, energy technologies, material sciences, medical technologies, and other fields. However, with the wide application and increasing production of CNTs, their potential risks have led to concerns regarding their impact on environment and health. The shape of some types of CNTs is similar to asbestos fibers, which suggests that these CNTs may cause characteristic pleural diseases similar to those found in asbestos-exposed humans, such as pleural plaques and malignant mesothelioma. Experimental data indicate that CNTs can induce lung and pleural lesions, inflammation, pleural fibrosis, lung tumors, and malignant mesothelioma upon inhalation in the experimental animals. In this review, we focus on the potential of MWCNTs to induce diseases similar to those by asbestos, molecular and cellular mechanisms associated with these diseases, and we discuss a method for evaluating the pleural toxicity of MWCNTs.}, } @article {pmid32760782, year = {2020}, author = {Plesker, R and Köhler, K and von Gerlach, S and Boller, K and Vogt, M and Feder, IS}, title = {Reactive mesothelial hyperplasia mimicking mesothelioma in an African green monkey (Chlorocebus aethiops).}, journal = {Primate biology}, volume = {7}, number = {1}, pages = {5-12}, pmid = {32760782}, issn = {2363-4715}, abstract = {A spontaneous reactive mesothelial hyperplasia occurred in a female, 15.7-year-old African green monkey (grivet; Chlorocebus aethiops). At necropsy, massive effusions were found in the abdomen, the thorax, and the pericardium. Additionally, multiple small, beige-gray nodules were detected on the serosal surfaces of the abdominal organs. Histopathologically, the mesothelial cells resembled the epithelioid subtype of a mesothelioma, but no infiltrative or invasive growth could be demonstrated. The mesothelial cells on the thoracis, liver, and intestinal serosa were accompanied by chronic serositis. Mesothelial cells expressed cytokeratin, vimentin, calretinin, desmin, Wilms Tumor 1 (WT-1) protein, and epithelial membrane antigen (EMA). Cells were negative for carcinoembryonic antigen (CEA), cluster of differentiation 15 (CD15), and podoplanin. Ultrastructurally, cells revealed a moderate amount of microvilli of medium length, perinuclear tonofilament bundles, and long desmosomes. In fluorescence in situ hybridization (FISH) for the detection of characteristic gene loss (p16; CDKN2A), NF2, and MTAP, no deletions were detected. No asbestos fibers and no presence of Simian virus 40 antigen (SV40) could be demonstrated.}, } @article {pmid32759747, year = {2020}, author = {Marzullo, A and Serio, G and Pezzuto, F and Fortarezza, F and Cazzato, G and Caporusso, C and Lettini, T and Cavone, D and Delfino, MC and Vimercati, L}, title = {A Single Liver Metastasis from Pleural Biphasic Mesothelioma.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {10}, number = {8}, pages = {}, pmid = {32759747}, issn = {2075-4418}, abstract = {Virtually any malignancy can metastasize to the liver. Large solitary metastases are rare and can be difficult to distinguish from primary tumors. Malignant mesothelioma is often considered as a locally invasive cancer but tumor dissemination to extra-thoracic sites is possible, and the liver can be involved. Herein, we present a rare case of pleural mesothelioma with a solitary large liver metastasis diagnosed postmortem in a ninety-two-year-old man with 35 years of exposure to asbestos. Results of immunohistochemical staining of the pleural and liver tumor were similar, both positive for low-molecular weight keratins, calretinin, vimentin, and podoplanin, and negative for Claudin-4, TTF1, CEA, BerEP4, CK7, CK19, CK20, BAP1, Hep Par1, p40, and WT1. Fluorescent in-situ hybridization (FISH) for p16/CDKN2A was also performed and a homozygous deletion was detected in both tumors, supporting the diagnosis of mesothelioma. Reporting this case, we would like to point out that extra-thoracic dissemination from pleural mesothelioma, even if exceptional, can occur. In cases where differential diagnoses are challenging, the value of ancillary techniques and a practical approach to diagnostic work-up is of primary importance.}, } @article {pmid32755622, year = {2020}, author = {Luo, Y and Deng, J and Cui, Y and Li, T and Bai, J and Huang, L and Sun, Y and Dong, F and Zhang, Q}, title = {Long-term instillation to four natural representative chrysotile of China induce the inactivation of P53 and P16 and the activation of C-JUN and C-FOS in the lung tissues of Wistar rats.}, journal = {Toxicology letters}, volume = {333}, number = {}, pages = {140-149}, doi = {10.1016/j.toxlet.2020.07.033}, pmid = {32755622}, issn = {1879-3169}, mesh = {Animals ; Asbestos, Serpentine/chemistry/*toxicity ; Bronchoalveolar Lavage Fluid/cytology ; China ; Cyclin-Dependent Kinase Inhibitor p16/genetics/*metabolism ; Cytokines/metabolism ; Environmental Pollutants/chemistry/*toxicity ; Gene Expression/drug effects ; Inhalation Exposure/adverse effects ; JNK Mitogen-Activated Protein Kinases/genetics/*metabolism ; Leukocyte Count ; Leukocytes/cytology/drug effects ; Lung/*drug effects/immunology/metabolism/pathology ; Male ; Mineral Fibers/toxicity ; Proto-Oncogene Proteins c-fos/genetics/*metabolism ; Rats, Wistar ; Tumor Suppressor Protein p53/genetics/*metabolism ; }, abstract = {Chrysotile is the only type of asbestos still widely exploited, and all kinds of asbestos including chrysotile was classified as a group I carcinogen by the IARC. There is a wealth of evidence that chrysotile can cause a range of cancers, including cancer of the lung, larynx, ovary, and mesothelioma. As the second largest chrysotile producer, China is at great risk of occupational exposure. Moreover, our previous experiment and some other studies have shown that the toxicity of mineral fibre from various mining areas may be different. To explore the oncogenic potential of chrysotile from different mining areas of China, Wistar rats were administered 0.5 mL chrysotile asbestos suspension of 2.0 mg/mL (from Akesai, Gansu; Mangnai, Qinghai; XinKang, Sichuan; and Shannan, Shaanxi) dissolved in saline by intratracheal instillation once-monthly and were sacrificed at 1 mo, 6 mo, and 12 mo. Our results found that chrysotile caused lung inflammation and lung tissue damage. Moreover, prolonged exposure of chrysotile can induce inactivation of the tumor suppressor gene P53 and P16 and activation of the protooncogene C-JUN and C-FOS both in the messenger RNA and protein level. In addition, chrysotile from Shannan and XinKang has a stronger effect which may link to cancer than that from Akesai and Mangnai.}, } @article {pmid32732250, year = {2020}, author = {Cerciello, F and Choi, M and Sinicropi-Yao, SL and Lomeo, K and Amann, JM and Felley-Bosco, E and Stahel, RA and Robinson, BWS and Creaney, J and Pass, HI and Vitek, O and Carbone, DP}, title = {Verification of a Blood-Based Targeted Proteomics Signature for Malignant Pleural Mesothelioma.}, journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology}, volume = {29}, number = {10}, pages = {1973-1982}, pmid = {32732250}, issn = {1538-7755}, support = {U01 CA111295/CA/NCI NIH HHS/United States ; U01 CA214195/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Female ; Humans ; Male ; Mass Spectrometry/*methods ; Mesothelioma, Malignant/*genetics ; Middle Aged ; Pleural Neoplasms/*genetics ; Proteomics/*methods ; }, abstract = {BACKGROUND: We have verified a mass spectrometry (MS)-based targeted proteomics signature for the detection of malignant pleural mesothelioma (MPM) from the blood.

METHODS: A seven-peptide biomarker MPM signature by targeted proteomics in serum was identified in a previous independent study. Here, we have verified the predictive accuracy of a reduced version of that signature, now composed of six-peptide biomarkers. We have applied liquid chromatography-selected reaction monitoring (LC-SRM), also known as multiple-reaction monitoring (MRM), for the investigation of 402 serum samples from 213 patients with MPM and 189 cancer-free asbestos-exposed donors from the United States, Australia, and Europe.

RESULTS: Each of the biomarkers composing the signature was independently informative, with no apparent functional or physical relation to each other. The multiplexing possibility offered by MS proteomics allowed their integration into a single signature with a higher discriminating capacity than that of the single biomarkers alone. The strategy allowed in this way to increase their potential utility for clinical decisions. The signature discriminated patients with MPM and asbestos-exposed donors with AUC of 0.738. For early-stage MPM, AUC was 0.765. This signature was also prognostic, and Kaplan-Meier analysis showed a significant difference between high- and low-risk groups with an HR of 1.659 (95% CI, 1.075-2.562; P = 0.021).

CONCLUSIONS: Targeted proteomics allowed the development of a multianalyte signature with diagnostic and prognostic potential for MPM from the blood.

IMPACT: The proteomic signature represents an additional diagnostic approach for informing clinical decisions for patients at risk for MPM.}, } @article {pmid32731396, year = {2020}, author = {Javadi, J and Dobra, K and Hjerpe, A}, title = {Multiplex Soluble Biomarker Analysis from Pleural Effusion.}, journal = {Biomolecules}, volume = {10}, number = {8}, pages = {}, pmid = {32731396}, issn = {2218-273X}, support = {CAN 2018/653//Cancerfonden/International ; }, mesh = {Adenocarcinoma/diagnosis/*pathology ; Biomarkers, Tumor/analysis ; Humans ; Lung Neoplasms/diagnosis/*pathology ; Mesothelioma, Malignant/diagnosis/*pathology ; Pleural Effusion/diagnosis/*pathology ; Prognosis ; }, abstract = {Malignant pleural mesothelioma (MPM) is a highly aggressive and therapy resistant pleural malignancy that is caused by asbestos exposure. MPM is associated with poor prognosis and a short patient survival. The survival time is strongly influenced by the subtype of the tumor. Dyspnea and accumulation of pleural effusion in the pleural cavity are common symptoms of MPM. The diagnostic distinction from other malignancies and reactive conditions is done using histopathology or cytopathology, always supported by immunohistochemistry, and sometimes also by analyses of soluble biomarkers in effusion supernatant. We evaluated the soluble angiogenesis related molecules as possible prognostic and diagnostic biomarkers for MPM by Luminex multiplex assay. Pleural effusion from 42 patients with malignant pleural mesothelioma (MPM), 36 patients with adenocarcinoma (AD) and 40 benign (BE) effusions were analyzed for 10 different analytes that, in previous studies, were associated with angiogenesis, consisting of Angiopoietin-1, HGF, MMP-7, Osteopontin, TIMP-1, Galectin, Mesothelin, NRG1-b1, Syndecan-1 (SDC-1) and VEGF by a Human Premixed Multi-Analyte Luminex kit. We found that shed SDC-1 and MMP-7 levels were significantly lower, whereas Mesothelin and Galectin-1 levels were significantly higher in malignant mesothelioma effusions, compared to adenocarcinoma. Galectin-1, HGF, Mesothelin, MMP-7, Osteopontin, shed SDC-1, NRG1-β1, VEGF and TIMP-1 were significantly higher in malignant pleural mesothelioma effusions compared to benign samples. Moreover, there is a negative correlation between Mesothelin and shed SDC-1 and positive correlation between VEGF, Angiopoietin-1 and shed SDC-1 level in the pleural effusion from malignant cases. Shed SDC-1 and VEGF have a prognostic value in malignant mesothelioma patients. Collectively, our data suggest that MMP-7, shed SDC-1, Mesothelin and Galectin-1 can be diagnostic and VEGF and SDC-1 prognostic markers in MPM patients. Additionally, Galectin-1, HGF, Mesothelin, MMP-7, Osteopontin, shed SDC-1 and TIMP-1 can be diagnostic for malignant cases.}, } @article {pmid32727552, year = {2020}, author = {Lehnert, M and Weber, DG and Taeger, D and Raiko, I and Kollmeier, J and Stephan-Falkenau, S and Brüning, T and Johnen, G and , }, title = {Determinants of plasma calretinin in patients with malignant pleural mesothelioma.}, journal = {BMC research notes}, volume = {13}, number = {1}, pages = {359}, pmid = {32727552}, issn = {1756-0500}, support = {IN-1214264//Ruhr-Universität Bochum/ ; }, mesh = {Calbindin 2 ; Cross-Sectional Studies ; Humans ; *Mesothelioma/diagnosis ; *Mesothelioma, Malignant ; *Pleural Neoplasms/diagnosis ; }, abstract = {OBJECTIVE: Calretinin is a well-known immunohistochemical tissue marker in the diagnosis of malignant mesothelioma. Promising results also indicate the use in early detection. In the present cross-sectional survey, correlations of calretinin plasma levels with clinical features were investigated. Plasma samples of 60 patients with malignant pleural mesothelioma (MPM) and 111 cancer-free controls formerly exposed to asbestos were compared. Calretinin concentrations were determined in plasma using an enzyme-linked immunosorbent assay (ELISA).

RESULTS: The median concentration was higher in MPM patients than in controls (0.79 vs. 0.23 ng/ml; p < 0.0001). Patients with epithelioid MPM or biphasic MPM had higher calretinin plasma levels than patients with sarcomatoid MPM. Strong expression of calretinin in the tumor tissue was associated with higher plasma levels. Preoperative patients showed higher levels of calretinin than patients after thoracic surgery (1.20 vs. 0.67 ng/ml; p = 0.096). The suitability of plasma calretinin has been confirmed as a tumor marker in the differential diagnosis of epithelioid MPM. The value of plasma calretinin for therapy monitoring or as a prognostic marker should be further investigated.}, } @article {pmid32726334, year = {2020}, author = {Schüz, J and Bukhtiyarov, I and Olsson, A and Moissonnier, M and Ostroumova, E and Feletto, E and Schonfeld, SJ and Byrnes, G and Tskhomariia, I and McCormack, V and Straif, K and Kashanskiy, S and Morozova, T and Kromhout, H and Kovalevskiy, E}, title = {Occupational cohort study of current and former workers exposed to chrysotile in mine and processing facilities in Asbest, the Russian Federation: Cohort profile of the Asbest Chrysotile Cohort study.}, journal = {PloS one}, volume = {15}, number = {7}, pages = {e0236475}, pmid = {32726334}, issn = {1932-6203}, support = {001/WHO_/World Health Organization/International ; }, mesh = {Adult ; Asbestos/adverse effects ; Asbestos, Serpentine/*adverse effects ; Cohort Studies ; Female ; Humans ; Lung Neoplasms/chemically induced/*epidemiology/pathology ; Male ; Mesothelioma/chemically induced/*epidemiology/pathology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Diseases/chemically induced/*epidemiology/pathology ; Occupational Exposure/*adverse effects ; Russia/epidemiology ; }, abstract = {A historical cohort study in workers occupationally exposed to chrysotile was set up in the town of Asbest, the Russian Federation, to study their cause-specific mortality, with a focus on cancer. Chrysotile has different chemical and physical properties compared with other asbestos fibres; therefore it is important to conduct studies specifically of chrysotile and in different geographical regions to improve the knowledge about its carcinogenicity. Setting was the town of Asbest, Sverdlovsk oblast, the Russian Federation. Participants were all current and former employees with at least one year of employment between 1/1/1975 and 31/12/2010 in the mine, enrichment factories, auto-transport and external rail transportation departments, the central laboratory, and the explosives unit of the company. Of the 35,837 cohort members, 12,729 (35.5%) had died (2,373 of them of cancer, including 10 of mesothelioma), 18,799 (52.5%) were known to be alive at the end of the observation period (2015), and 4,309 (12.0%) were censored before the end of 2015. Mean follow-up duration was 21.7 years in men and 25.9 years in women. The mean age at death was 59.4 years in men and 66.5 years in women. This is the largest occupational cohort of chrysotile workers to date, and the only one with a large proportion of exposed female workers.}, } @article {pmid32723839, year = {2020}, author = {Kwak, K and Paek, D and Zoh, KE}, title = {Author's response to 'Re: Exposure to asbestos and the risk of colorectal cancer mortality: a systematic review and meta-analysis by Kwak et al'.}, journal = {Occupational and environmental medicine}, volume = {77}, number = {9}, pages = {656-657}, doi = {10.1136/oemed-2020-106737}, pmid = {32723839}, issn = {1470-7926}, mesh = {*Asbestos/adverse effects ; *Colonic Neoplasms ; *Colorectal Neoplasms ; Humans ; *Mesothelioma ; }, } @article {pmid32710945, year = {2020}, author = {Gandhi, M and Nair, S}, title = {New vistas in malignant mesothelioma: MicroRNA architecture and NRF2/MAPK signal transduction.}, journal = {Life sciences}, volume = {257}, number = {}, pages = {118123}, doi = {10.1016/j.lfs.2020.118123}, pmid = {32710945}, issn = {1879-0631}, mesh = {Animals ; Biomarkers, Tumor ; Humans ; Lung Neoplasms/*metabolism ; *MAP Kinase Signaling System ; Mesothelioma/*metabolism ; Mesothelioma, Malignant ; MicroRNAs/*metabolism ; NF-E2-Related Factor 2/*metabolism ; }, abstract = {Malignant mesothelioma (MM) is a cancer of the mesothelial lining of the pleura, peritoneum, pericardium and testes. The most common form is asbestos-linked MM that is etiologically linked to repeated asbestos exposure with a long latency period, although non-asbestos MM has also been reported. Late diagnosis, poor survival rates, lack of diagnostic and prognostic markers act as major impediments in the clinical management of MM. Despite advances in immune checkpoint inhibition and CAR T-cell-based therapies, MM which is of different histologic subtypes remains challenging to treat. We review microRNAs (miRNAs) and the miRNA interactome implicated in MM which can be useful as circulating miRNA biomarkers for early diagnosis of MM and as biomarkers for prognostication in MM. Further, we underscore the relevance of the NRF2/MAPK signal transduction pathway that has been implicated in MM which may be useful as druggable targets or as biomarkers of predictive response. In addition, since MM is driven partly by inflammation, we elucidate chemopreventive phytochemicals that are beneficial in MM, either via crosstalk with the NRF2/MAPK pathway or via concerted anticancer mechanisms, and may be of benefit as adjuvants in chemotherapy. Taken together, a multifactorial approach comprising identification of miRNA target hubs and NRF2/MAPK biomarkers along with appropriately designed clinical trials may enable early detection and faster intervention in MM translating into better patient outcomes for this aggressive cancer.}, } @article {pmid32709739, year = {2020}, author = {Boffetta, P}, title = {Re: Exposure to asbestos and the risk of colorectal cancer mortality: a systematic review and meta-analysis by Kwak et al.}, journal = {Occupational and environmental medicine}, volume = {77}, number = {9}, pages = {655}, doi = {10.1136/oemed-2020-106588}, pmid = {32709739}, issn = {1470-7926}, mesh = {*Asbestos/adverse effects ; *Colonic Neoplasms ; *Colorectal Neoplasms/etiology ; Humans ; *Mesothelioma ; }, } @article {pmid32708306, year = {2020}, author = {Bonelli, M and Terenziani, R and Zoppi, S and Fumarola, C and La Monica, S and Cretella, D and Alfieri, R and Cavazzoni, A and Digiacomo, G and Galetti, M and Petronini, PG}, title = {Dual Inhibition of CDK4/6 and PI3K/AKT/mTOR Signaling Impairs Energy Metabolism in MPM Cancer Cells.}, journal = {International journal of molecular sciences}, volume = {21}, number = {14}, pages = {}, pmid = {32708306}, issn = {1422-0067}, support = {N/A//Associazione Augusto per la Vita (Novellara, RE)/ ; N/A//CHIESI Farmaceutici S.p.A. (Parma)/ ; N/A//Transfer Oil S.p.A. (Colorno, PR)/ ; N/A//Famiglia Gigetto Furlotti (Parma)/ ; N/A//A.VO.PRO.RI.T. (Parma)/ ; N/A//Ing. Marco Nocivelli, EPTA S.p.A (Milano)/ ; 2018.0184//Fondazione CARIPARMA/ ; }, mesh = {Cell Line, Tumor ; Cell Proliferation/*drug effects ; Cyclin-Dependent Kinase 4/*antagonists & inhibitors ; Cyclin-Dependent Kinase 6/*antagonists & inhibitors ; Energy Metabolism/*drug effects ; Glycolysis/drug effects ; Humans ; Mesothelioma, Malignant/drug therapy/*metabolism ; Mitochondria/drug effects/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphoinositide-3 Kinase Inhibitors/pharmacology ; Piperazines/pharmacology ; Pleural Neoplasms/drug therapy/*metabolism ; Protein Kinase Inhibitors/*pharmacology ; Proto-Oncogene Proteins c-akt/antagonists & inhibitors/metabolism ; Pyridines/pharmacology ; Signal Transduction/drug effects ; TOR Serine-Threonine Kinases/*antagonists & inhibitors/metabolism ; }, abstract = {Background: Malignant pleural mesothelioma (MPM) is an aggressive malignancy associated to asbestos exposure. One of the most frequent genetic alteration in MPM patients is CDKN2A/ARF loss, leading to aberrant activation of the Rb pathway. In MPM cells, we previously demonstrated the therapeutic efficacy of targeting this signaling with the CDK4/6 inhibitor palbociclib in combination with PI3K/mTOR inhibitors. Here, we investigated whether such combination may have an impact on cell energy metabolism. Methods: The study was performed in MPM cells of different histotypes; metabolic analyses were conducted by measuring GLUT-1 expression and glucose uptake/consumption, and by SeaHorse technologies. Results: MPM cell models differed for their ability to adapt to metabolic stress conditions, such as glucose starvation and hypoxia. Independently of these differences, combined treatments with palbociclib and PI3K/mTOR inhibitors inhibited cell proliferation more efficaciously than single agents. The drugs alone reduced glucose uptake/consumption as well as glycolysis, and their combination further enhanced these effects under both normoxic and hypoxic conditions. Moreover, the drug combinations significantly impaired mitochondrial respiration as compared with individual treatments. These metabolic effects were mediated by the concomitant inhibition of Rb/E2F/c-myc and PI3K/AKT/mTOR signaling. Conclusions: Dual blockade of glycolysis and respiration contributes to the anti-tumor efficacy of palbociclib-PI3K/mTOR inhibitors combination.}, } @article {pmid32700418, year = {2020}, author = {Voloaca, OM and Greenhalgh, CJ and Cole, LM and Clench, MR and Managh, AJ and Haywood-Small, SL}, title = {Laser ablation inductively coupled plasma mass spectrometry as a novel clinical imaging tool to detect asbestos fibres in malignant mesothelioma.}, journal = {Rapid communications in mass spectrometry : RCM}, volume = {34}, number = {21}, pages = {e8906}, doi = {10.1002/rcm.8906}, pmid = {32700418}, issn = {1097-0231}, mesh = {*Asbestos/analysis/chemistry ; Cell Line, Tumor ; Humans ; Lasers ; *Lung Neoplasms/diagnostic imaging/pathology ; Mass Spectrometry/*methods ; *Mesothelioma, Malignant/diagnostic imaging/pathology ; Microscopy/*methods ; }, abstract = {RATIONALE: Malignant pleural mesothelioma is an extremely aggressive and incurable malignancy associated with prior exposure to asbestos fibres. Difficulties remain in relation to early diagnosis, notably due to impeded identification of asbestos in lung tissue. This study describes a novel laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) imaging approach to identify asbestos within mesothelioma models with clinical significance.

METHODS: Human mesothelioma cells were exposed to different types of asbestos fibres and prepared on plastic slides for LA-ICP-MS analysis. No further sample preparation was required prior to analysis, which was performed using an NWR Image 266 nm laser ablation system coupled to an Element XR sector-field ICP mass spectrometer, with a lateral resolution of 2 μm. Data was processed using LA-ICP-MS ImageTool v1.7 with the final graphic production made using DPlot software.

RESULTS: Four different mineral fibres were successfully identified within the mesothelioma samples based on some of the most abundant elements that make up these fibres (Si, Mg and Fe). Using LA-ICP-MS as an imaging tool provided information on the spatial distribution of the fibres at cellular level, which is essential in asbestos detection within tissue samples. Based on the metal counts generated by the different types of asbestos, different fibres can be identified based on shape, size, and elemental composition. Detection of Ca was attempted but requires further optimisation.

CONCLUSIONS: Detection of asbestos fibres in lung tissues is very useful, if not necessary, to complete the pathological dt9iagnosis of asbestos-related malignancies in the medicolegal field. For the first time, this study demonstrates the successful application of LA-ICP-MS imaging to identify asbestos fibres and other mineral fibres within mesothelioma samples. Ultimately, high-resolution, fast-speed LA-ICP-MS analysis has the potential to be integrated into clinical workflow to aid earlier detection and stratification of mesothelioma patient samples.}, } @article {pmid32699075, year = {2020}, author = {Pass, HI and Alimi, M and Carbone, M and Yang, H and Goparaju, CM}, title = {Mesothelioma Biomarkers: A Review Highlighting Contributions from the Early Detection Research Network.}, journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology}, volume = {29}, number = {12}, pages = {2524-2540}, doi = {10.1158/1055-9965.EPI-20-0083}, pmid = {32699075}, issn = {1538-7755}, support = {U01 CA214195/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers, Tumor/*metabolism ; Early Detection of Cancer/*methods ; Female ; Humans ; Male ; Mesothelioma/*diagnosis/pathology ; }, abstract = {Malignant pleural mesothelioma (MPM) is an asbestos-related neoplasm, which can be treated successfully only if correctly diagnosed and treated in early stages. The asbestos-exposed population serves as a high-risk group that could benefit from sensitive and specific blood- or tissue-based biomarkers. This review details the recent work with biomarker development in MPM and the contributions of the NCI Early Detection Research Network Biomarker Developmental Laboratory of NYU Langone Medical Center. The literature of the last 20 years was reviewed to comment on the most promising of the blood- and tissue-based biomarkers. Proteomic, genomic, and epigenomic platforms as well as novel studies such as "breath testing" are covered. Soluble mesothelin-related proteins (SMRP) have been characterized extensively and constitute an FDA-approved biomarker in plasma with diagnostic, monitoring, and prognostic value in MPM. Osteopontin is found to be a valuable prognostic biomarker for MPM, while its utility in diagnosis is slightly lower. Other biomarkers, such as calretinin, fibulin 3, and High-Mobility Group Box 1 (HMGB1), remain under study and need international validation trials with large cohorts of cases and controls to demonstrate any utility. The EDRN has played a key role in the development and testing of MPM biomarkers by enlisting collaborations all over the world. A comprehensive understanding of previously investigated biomarkers and their utility in screening and early diagnosis of MPM will provide guidance for further future research.See all articles in this CEBP Focus section, "NCI Early Detection Research Network: Making Cancer Detection Possible."}, } @article {pmid32691574, year = {2020}, author = {Loreto, C and Ledda, C and Tumino, R and Lombardo, C and Vitale, E and Filetti, V and Caltabiano, R and Rapisarda, V}, title = {Activation of caspase-3 in malignant mesothelioma induced by asbestiform fiber: an in vivo study.}, journal = {Journal of biological regulators and homeostatic agents}, volume = {34}, number = {3}, pages = {1163-1166}, doi = {10.23812/19-441-L-50}, pmid = {32691574}, issn = {0393-974X}, mesh = {Caspase 3/genetics ; Humans ; Italy ; *Lung Neoplasms/genetics ; *Mesothelioma/genetics ; }, } @article {pmid32690542, year = {2020}, author = {Carbone, M and Harbour, JW and Brugarolas, J and Bononi, A and Pagano, I and Dey, A and Krausz, T and Pass, HI and Yang, H and Gaudino, G}, title = {Biological Mechanisms and Clinical Significance of BAP1 Mutations in Human Cancer.}, journal = {Cancer discovery}, volume = {10}, number = {8}, pages = {1103-1120}, pmid = {32690542}, issn = {2159-8290}, support = {R01 CA198138/CA/NCI NIH HHS/United States ; R01 CA237235/CA/NCI NIH HHS/United States ; R01 CA125970/CA/NCI NIH HHS/United States ; P50 CA196516/CA/NCI NIH HHS/United States ; P30 CA240139/CA/NCI NIH HHS/United States ; U01 CA111295/CA/NCI NIH HHS/United States ; U01 CA214195/CA/NCI NIH HHS/United States ; R01 ES030948/ES/NIEHS NIH HHS/United States ; P30 CA071789/CA/NCI NIH HHS/United States ; P30 EY014801/EY/NEI NIH HHS/United States ; R01 CA175754/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Kidney Neoplasms ; *Melanoma ; Mutation ; *Skin Neoplasms ; Tumor Suppressor Proteins/genetics ; Ubiquitin Thiolesterase/genetics ; *Uveal Neoplasms ; }, abstract = {Among more than 200 BAP1-mutant families affected by the "BAP1 cancer syndrome," nearly all individuals inheriting a BAP1 mutant allele developed one or more malignancies during their lifetime, mostly uveal and cutaneous melanoma, mesothelioma, and clear-cell renal cell carcinoma. These cancer types are also those that, when they occur sporadically, are more likely to carry somatic biallelic BAP1 mutations. Mechanistic studies revealed that the tumor suppressor function of BAP1 is linked to its dual activity in the nucleus, where it is implicated in a variety of processes including DNA repair and transcription, and in the cytoplasm, where it regulates cell death and mitochondrial metabolism. BAP1 activity in tumor suppression is cell type- and context-dependent. BAP1 has emerged as a critical tumor suppressor across multiple cancer types, predisposing to tumor development when mutated in the germline as well as somatically. Moreover, BAP1 has emerged as a key regulator of gene-environment interaction.This article is highlighted in the In This Issue feature, p. 1079.}, } @article {pmid32683434, year = {2020}, author = {Brook, MS and Black, PM and Salmond, J and Dirks, KN and Berry, TA and Steinhorn, G}, title = {Erionite in Auckland bedrock and malignant mesothelioma: an emerging public and occupational health hazard?.}, journal = {The New Zealand medical journal}, volume = {133}, number = {1518}, pages = {73-78}, pmid = {32683434}, issn = {1175-8716}, mesh = {Humans ; Incidence ; Lung Neoplasms/*chemically induced/epidemiology ; Mesothelioma/*chemically induced/epidemiology ; Mesothelioma, Malignant ; New Zealand/epidemiology ; Occupational Exposure/*adverse effects ; *Occupational Health ; *Public Health ; Zeolites/*adverse effects ; }, abstract = {Overseas, emerging research has shown that where erionite is present in bedrock as a zeolite, and then subsequently disturbed and blown into the atmosphere, resulting exposure is associated with health effects similar to those caused by asbestos, including malignant mesothelioma (MM). Erionite-induced MM is thought to be particularly prevalent in the construction and quarrying industries, in regions where rock containing erionite is disturbed. In 2015, the then Government Chief Scientist, Sir Peter Gluckman, reported that erionite was a more potent carcinogen than asbestos, and more recent studies have established its presence in the Auckland Region. However, globally at present, there are no established occupational exposure limits for erionite, standard sampling and analytical methods or exposure mitigation guidelines. Given the many major construction projects being carried out in Auckland at the present time, which involve the removal of large quantities of bedrock containing erionite, an assessment of the health risks such activities pose to the public is needed.}, } @article {pmid32682370, year = {2020}, author = {Cheng, L and Li, N and Xu, XL and Mao, WM}, title = {Progress in the Understanding of the Immune Microenvironment and Immunotherapy in Malignant Pleural Mesothelioma.}, journal = {Current drug targets}, volume = {21}, number = {15}, pages = {1606-1612}, doi = {10.2174/1389450121666200719011234}, pmid = {32682370}, issn = {1873-5592}, support = {81802995//National Natural Science Foundation of China/ ; 2018RC020, 2018KY024//Medical Science and Technology Project of Zhejiang Province/ ; }, mesh = {Animals ; B7-H1 Antigen/metabolism ; Cancer-Associated Fibroblasts/immunology ; Dendritic Cells/immunology ; Humans ; *Immunotherapy ; Killer Cells, Natural/immunology ; Mesothelioma, Malignant/*immunology/*therapy ; Myeloid-Derived Suppressor Cells/immunology ; T-Lymphocytes/immunology ; Tumor Microenvironment/*immunology ; Tumor-Associated Macrophages/immunology ; }, abstract = {Malignant pleural mesothelioma (MPM) is a remarkably aggressive thoracic malignancy with a limited survival of only 5-12 months. However, MPM still remains unresponsive to conventional standards of treatment, including pleurectomy and decortication, extrapleural pneumonectomy for resectable disease with or without chemotherapy, and/or radiation therapy. The mechanism of carcinogenesis has not been fully elucidated, although approximately 80% of cases can still be linked to asbestos exposure. The tumor immune microenvironment (TME) has been proven to play an important role in MPM pathogenesis and treatment outcomes. Several molecular pathways have been implicated in the MPM tumor microenvironment, such as angiogenesis, apoptosis, cell cycle regulation, and stromal processes. Immunotherapy has already shown promising results in other thoracic solid tumors, such as non-small-cell lung cancer (NSCLC). However, immunotherapy has shown less convincing results in MPM than in melanoma and NSCLC. A multicenter, randomized trial (DETERMINE) proved that immune checkpoint inhibition using tremelimumab, an anti-cytotoxic T lymphocyteassociated protein 4 (CTLA-4) antibody, failed to improve median overall survival. Therefore, it is important to explore the relationship between the characteristics of the tumor microenvironment and immunotherapy. Here, we review the heterogeneity of the TME and the progress in the understanding of the immune microenvironment and immunotherapy in MPM to explore the mechanisms of resistance to immunotherapy.}, } @article {pmid32682189, year = {2020}, author = {Remon, J and Nadal, E and Dómine, M and Ruffinelli, J and García, Y and Pardo, JC and López, R and Cilleruelo, A and García-Campelo, R and Martín, P and Juan, O and González-Larriba, JL and Provencio, M and Olmedo, E and Ponce, S and Cumplido, D and Barenys, C and Majem, M and Massutti, B and Rodriguez-Abreu, D and Porta, R and Sala, MA and Martinez-Kareaga, M and Lianes, P and Reguart, N}, title = {Malignant pleural mesothelioma: Treatment patterns and outcomes from the Spanish Lung Cancer Group.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {147}, number = {}, pages = {83-90}, doi = {10.1016/j.lungcan.2020.06.034}, pmid = {32682189}, issn = {1872-8332}, mesh = {Humans ; *Lung Neoplasms/diagnosis/epidemiology/therapy ; *Mesothelioma/diagnosis/epidemiology/therapy ; *Mesothelioma, Malignant ; *Pleural Neoplasms/epidemiology/therapy ; Spain/epidemiology ; }, abstract = {BACKGROUND: Malignant mesothelioma is a rare but aggressive tumor arising from the pleura, typically associated with exposure to asbestos. The purpose of this investigation was to describe mesothelioma patient characteristics, treatment patterns, and outcomes in Spain.

MATERIAL AND METHODS: Patients diagnosed with malignant mesothelioma of the pleura were recorded in an anonymous online database (BEMME, Epidemiologic Spanish Malignant Mesothelioma Database) from June 2008 through May 2013. Patient and tumor characteristics at time of diagnosis, as well as subsequent treatments (surgery, radiation, and chemotherapy), were collected. Among patients treated with chemotherapy, we explored type of chemotherapy regimen and outcomes by treatments.

RESULTS: A total of 560 malignant pleural mesothelioma (MPM) patients were recorded. The median age at diagnosis was 68 years, mainly with epithelioid histology (62 %), and any asbestos exposure was noted in 45 % of patients. Nearly two-thirds of patients (71 %) received chemotherapy, mainly platinum-pemetrexed combination, as part of their treatment. Surgery and radiotherapy were given in 36 % and 17 % of patients, respectively. The median overall survival (OS) in the whole cohort was 13.0 months (95 % confidence interval (CI), 11.1-14.8 months) with 1-year OS of 53.2 % (95 % CI, 48.7-57.7 %). In patients receiving first-line chemotherapy (N = 315), the median OS was 13.4 months (95 % CI, 10.8-16.0 months), reaching 20.2 months (95 % CI, 17.2-23.2 months) for those 68 patients receiving maintenance chemotherapy. Results of multivariate analyses showed significant association of ECOG-performance status, histology and treatment response with improved OS in MPM patients treated with palliative chemotherapy.

CONCLUSIONS: Despite multimodal therapeutic intervention, survival of patients with mesothelioma in Spain remains poor. Although it did not reach significance in the multivariate analysis, a meaningful additional survival benefit was observed among those patients receiving maintenance chemotherapy.}, } @article {pmid32676359, year = {2020}, author = {Hjerpe, A and Abd Own, S and Dobra, K}, title = {Integrative approach to cytologic and molecular diagnosis of malignant pleural mesothelioma.}, journal = {Translational lung cancer research}, volume = {9}, number = {3}, pages = {934-943}, pmid = {32676359}, issn = {2218-6751}, abstract = {The global incidence of malignant mesothelioma (MM) causes considerable disease burden, suffering and health care costs. Beside preventive measures and ban the use of asbestos, early diagnosis would largely improve the chance of curative treatment. Current histologic criteria, however, requiring presence of invasion in the surrounding fatty tissue fail to identify MM in sufficiently early stage. Unilateral accumulation of pleural effusion is one of the earliest clinical manifestations of MM that occurs in approximately 90% of the patients. Therapeutic thoracocenthesis is necessary to remove the fluid and to relieve patients' symptoms. This effusion is easily accessible and offers early and minimally invasive diagnosis by combining cytology with immunologic, molecular- and biomarker analyses. Typically, the fluid is rich in malignant cells and cell groups, but incipient stages of the disease may be difficult to recognize as the malignant cells can be masked by presence of inflammatory or reactive mesothelial cells. Recurrent, hemorrhagic and cell rich effusion should always be suspicious for MM and adequately prepared and analyzed to provide necessary information for subsequent therapy. Importantly, early detection of MM by integrating cytology and molecular approaches has high sensitivity and positive predictive value and has a major impact on patient survival. Thus, a conclusive positive MM cytology should lead to treatment without delay. This review summarizes molecular and diagnostic criteria of MM diagnosis.}, } @article {pmid34589956, year = {2020}, author = {Ahmadzada, T and Cooper, WA and Holmes, M and Mahar, A and Westman, H and Gill, AJ and Nordman, I and Yip, PY and Pal, A and Zielinski, R and Pavlakis, N and Nagrial, A and Daneshvar, D and Brungs, D and Karikios, D and Aleksova, V and Burn, J and Asher, R and Grau, GE and Hosseini-Beheshti, E and Reid, G and Clarke, S and Kao, S}, title = {Retrospective Evaluation of the Use of Pembrolizumab in Malignant Mesothelioma in a Real-World Australian Population.}, journal = {JTO clinical and research reports}, volume = {1}, number = {4}, pages = {100075}, pmid = {34589956}, issn = {2666-3643}, abstract = {INTRODUCTION: We investigated the efficacy and toxicity of pembrolizumab in patients with mesothelioma from a real-world Australian population. We aimed to determine clinical factors and predictive biomarkers that could help select patients who are likely to benefit from pembrolizumab.

METHOD: Patients with mesothelioma who were treated with pembrolizumab as part of the Insurance and Care New South Wales compensation scheme were included. Clinical information was collected retrospectively. Tumor biomarkers such as programmed death-ligand 1 (PD-L1), BAP1, and CD3-positive (CD3+) tumor-infiltrating lymphocytes (TILs) were examined using archival formalin-fixed paraffin-embedded tumor samples.

RESULTS: A total of 98 patients were included with a median age of 70 years (range, 46-91 y); 92% were men; 76% had epithelioid subtype; 21% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0. Pembrolizumab was used as second-line or subsequent-line treatment in 94 patients and as first-line treatment in four patients. The overall response rate was 18%, and the disease control rate was 56%. The median progression-free survival (PFS) was 4.8 months (95% confidence interval: 3.6-6.2), and the median overall survival (OS) was 9.5 months (95% confidence interval: 6.6-13.7). Immune-related adverse events occurred in 27% of patients, of which nine (9%) were of grade 3 or higher. In the multivariable analysis, factors independently associated with longer PFS included baseline ECOG status of 0 (median PFS: 12 mo versus 4 mo, p < 0.01) and PD-L1 tumor proportion score of greater than or equal to 1% (median PFS: 6 mo versus 4 mo, p < 0.01). Baseline platelet count of less than or equal to 400 × 10[9]/liter was independently associated with longer PFS and OS (median PFS: 6 mo versus 2 mo, p = 0.05; median OS: 10 mo versus 4 mo, p = 0.01), whereas lack of pretreatment dexamethasone was independently associated with OS but not PFS (median OS: 10 mo versus 3 mo, p = 0.01). The odds of response were higher for patients with baseline ECOG status of 0 (p = 0.02) and with greater than or equal to 5% CD3+ TILs in the tumor (p < 0.01). PD-L1 expression, BAP1 loss, and CD3+ TILs in the stroma were not significantly associated with the overall response rate.

CONCLUSIONS: Immunotherapy is a reasonable treatment option for patients with mesothelioma. Our results are comparable to other clinical trials investigating pembrolizumab in mesothelioma in terms of response. Good performance status assessment remains the most robust predictor for patient outcomes. CD3+ TILs in the tumor may help select patients that are likely to respond to pembrolizumab, whereas factors such as PD-L1 expression, baseline platelet count, and lack of pretreatment dexamethasone may help predict survival outcomes from pembrolizumab treatment.}, } @article {pmid32667289, year = {2020}, author = {Świątkowska, B}, title = {[The Amiantus Program in Poland - 20 years of implementation].}, journal = {Medycyna pracy}, volume = {71}, number = {5}, pages = {595-601}, doi = {10.13075/mp.5893.00997}, pmid = {32667289}, issn = {2353-1339}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Asbestosis/*diagnosis/epidemiology/*history/*prevention & control ; Female ; History, 21st Century ; Humans ; Male ; Mass Screening/history/methods/statistics & numerical data ; Middle Aged ; National Health Programs/*history ; Occupational Diseases/history/*prevention & control ; Occupational Exposure/history/*prevention & control ; Poland ; Population Surveillance/methods ; }, abstract = {BACKGROUND: Despite the ban on the production of asbestos-containing materials, introduced in Poland over 20 years ago, new cases of asbestos-related diseases are still being recorded. Systematic control of respiratory function in people exposed to asbestos dust is, therefore, extremely important due to the biological properties of this mineral.

MATERIAL AND METHODS: The Amiantus preventive medical examination program was undertaken in 2000 to implement the legal rights of former employees of asbestos processing plants for this type of examinations. People who have ever been employed in such factories have been authorized to use preventive medical examinations for the rest of their lives. The research is continuous, spread over time and focused, in particular, on the assessment of the respiratory system.

RESULTS: Since the beginning of the program, throughout 20 years of its implementation, 8329 people have been examined, including 5199 (62.4%) men for whom a total of 34 454 medical examinations have been carried out. During the program period, the percentage of diagnosed pathologies increased from 8% in 2000 to 25% in 2019. Overall, 2078 asbestos-related diseases were diagnosed among former employees of asbestos processing plants under the Amiantus Program, which accounted for 25% of this group. Among all diseases caused by exposure to asbestos, the most common were: asbestosis (1880 cases - 90.5%), lung cancer (121 cases - 5.8%) and pleural mesothelioma (77 cases - 3.7%). Diseases of pleura in the form of plaques and diffuse pleural thickening were diagnosed in 40% of the examined patients, while radiological pulmonary shadows affected over 65% of former employees of asbestos processing plants.

CONCLUSIONS: The Amiantus Program, thanks to the long observation period, enabled monitoring the health of former employees exposed to asbestos, and created a unique opportunity to carry out epidemiological analyzes. These studies allowed the authors to expand their knowledge of the natural history of asbestos-related diseases. Med Pr. 2020;71(5):595-601.}, } @article {pmid32664483, year = {2020}, author = {Indovina, P and Forte, IM and Pentimalli, F and Giordano, A}, title = {Targeting SRC Family Kinases in Mesothelioma: Time to Upgrade.}, journal = {Cancers}, volume = {12}, number = {7}, pages = {}, pmid = {32664483}, issn = {2072-6694}, support = {ID 483418//Mesothelioma Applied Research Foundation/ ; Ricerca Corrente (M4/7)//Italian Ministry of Health/ ; }, abstract = {Abstract: Malignant mesothelioma (MM) is a deadly tumor mainly caused by exposure to asbestos. Unfortunately, no current treatment is able to change significantly the natural history of the disease, which has a poor prognosis in the majority of patients. The non-receptor tyrosine kinase SRC and other SRC family kinase (SFK) members are frequently hyperactivated in many cancer types, including MM. Several works have indeed suggested that SFKs underlie MM cell proliferation, survival, motility, and invasion, overall affecting multiple oncogenic pathways. Consistently, SFK inhibitors effectively counteracted MM cancerous features at the preclinical level. Dasatinib, a multi-kinase inhibitor targeting SFKs, was also assessed in clinical trials either as second-line treatment for patients with unresectable MM or, more recently, as a neoadjuvant agent in patients with resectable MM. Here, we provide an overview of the molecular mechanisms implicating SFKs in MM progression and discuss possible strategies for a more successful clinical application of SFK inhibitors. Our aim is to stimulate discussion and further consideration of these agents in better designed preclinical and clinical studies to make the most of another class of powerful antitumoral drugs, which too often are lost in translation when applied to MM.}, } @article {pmid32649346, year = {2020}, author = {Louw, A and Creaney, J and Thomas, A and Van Vliet, C and Harvey, NT and Wood, BA and Mesbah Ardakani, N}, title = {Histologically Diverse BAP1-Deficient Melanocytic Tumors in a Patient With BAP1 Tumor Predisposition Syndrome.}, journal = {The American Journal of dermatopathology}, volume = {42}, number = {11}, pages = {872-875}, doi = {10.1097/DAD.0000000000001719}, pmid = {32649346}, issn = {1533-0311}, mesh = {Female ; Germ-Line Mutation ; Humans ; Melanoma/genetics/*pathology ; Mesothelioma/genetics ; Middle Aged ; Neoplastic Syndromes, Hereditary/*genetics/*pathology ; Pleural Neoplasms/genetics ; Skin Neoplasms/genetics/*pathology ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {BRCA1-associated protein-1 (BAP1)-deficient cutaneous tumors are common in patients with BAP1 tumor predisposition syndrome, frequently presenting before other associated neoplasms, and can serve as an early marker to identify individuals with this disease. The typical lesions are dermal based and composed of a combination of larger epithelioid melanocytes with abundant glassy cytoplasm and smaller cells resembling those of a conventional nevus. There is often a component of interspersed lymphocytes. However, BAP1-deficient melanocytic tumors can show a spectrum of histologic appearances, ranging from lesions with pure epithelioid, pure conventional nevus, or rhabdoid cells and tumors with an intraepidermal component. To demonstrate such morphologic variation, we present a case of a 50-year-old woman with multiple histologically diverse BAP1-deficient melanocytic tumors and germline BAP1 mutation, identified after a diagnosis of pleural mesothelioma. We also discuss the pathogenesis and potential histopathological and clinical indications of germline versus sporadic etiology in the assessment of BAP1-deficient melanocytic tumors.}, } @article {pmid32648970, year = {2020}, author = {Schüz, J and Kromhout, H}, title = {Re Ferrante et al (2020). Mortality and mesothelioma incidence among chrysotile asbestos miners in Balangero, Italy: A cohort study.}, journal = {American journal of industrial medicine}, volume = {63}, number = {9}, pages = {834-835}, doi = {10.1002/ajim.23154}, pmid = {32648970}, issn = {1097-0274}, support = {001/WHO_/World Health Organization/International ; }, mesh = {Asbestos, Serpentine ; Cohort Studies ; Humans ; Incidence ; Italy ; *Lung Neoplasms ; *Mesothelioma ; }, } @article {pmid32648944, year = {2020}, author = {Ferrante, D and Mirabelli, D and Silvestri, S and Azzolina, D and Giovannini, A and Tribaudino, P and Magnani, C}, title = {Ferrante et al respond.}, journal = {American journal of industrial medicine}, volume = {63}, number = {9}, pages = {836-837}, doi = {10.1002/ajim.23153}, pmid = {32648944}, issn = {1097-0274}, mesh = {*Asbestos, Serpentine ; Cohort Studies ; Humans ; Incidence ; Italy ; *Mesothelioma ; }, } @article {pmid32633902, year = {2020}, author = {Maat, A and Abdullah, S and Schouten, G and Cornelissen, R and Bogers, A and Mahtab, E}, title = {Video-assisted biopsy and talc pleurodesis for malignant pleural mesothelioma.}, journal = {Multimedia manual of cardiothoracic surgery : MMCTS}, volume = {2020}, number = {}, pages = {}, doi = {10.1510/mmcts.2020.038}, pmid = {32633902}, issn = {1813-9175}, mesh = {Aged ; Humans ; Image-Guided Biopsy/*methods ; *Lung Neoplasms/pathology/physiopathology/therapy ; Male ; *Mesothelioma/pathology/physiopathology/therapy ; Mesothelioma, Malignant ; Pleural Effusion, Malignant/etiology/prevention & control ; Pleurodesis/*methods ; Thoracic Surgery, Video-Assisted/*methods ; }, abstract = {Malignant pleural mesothelioma is a disease of the pleural cavity that is strongly associated with asbestos exposure. In most cases it carries a poor prognosis. Patients often present with respiratory symptoms, caused by pleural effusion. Treatment, preferably in a multimodal setting, cannot provide cure, but can prolong survival and improve quality of life in selected cases. Prior to eventual cytoreductive surgery, surgical intervention can provide histopathological proof of disease, and symptoms can be controlled with talc pleurodesis. We present the case of a 67-year-old patient with malignant pleural mesothelioma who underwent video-assisted thoracoscopic biopsy and talc pleurodesis, and demonstrate our technique with a video tutorial showing how we performed the procedure.}, } @article {pmid32631013, year = {2020}, author = {Fazzo, L and Cernigliaro, A and De Santis, M and Quattrone, G and Bruno, C and Zona, A and Tumino, R and Cascone, G and Scondotto, S and Comba, P}, title = {Occupational cohort study of asbestos-cement workers in a contaminated site in Sicily (Italy).}, journal = {Epidemiologia e prevenzione}, volume = {44}, number = {2-3}, pages = {137-144}, doi = {10.19191/EP20.2-3.P137.036}, pmid = {32631013}, issn = {1120-9763}, mesh = {Asbestos ; Asbestosis/*epidemiology ; Cohort Studies ; Construction Materials ; Female ; Humans ; Male ; Mesothelioma/epidemiology ; Middle Aged ; Occupational Diseases/*epidemiology ; Occupational Exposure/*statistics & numerical data ; Sicily/epidemiology ; }, abstract = {OBJECTIVES: to analyse the asbestos-related diseases risk among the former workers of Sacelit asbestos-cement plant, operating in San Filippo del Mela (Sicily: 1958- 1993).

DESIGN: cohort study.

SETTING AND PARTICIPANTS: 228 subjects were employed in Sacelit from 1958 to 1993. Due to the available observation periods, the analyses of the different outcomes were performed for the subjects alive at the beginning of the respective follow up periods: mortality (1986-2018) was analysed for 204 subjects (177 men, 27 women), hospitalization (2001-2016) for 164 workers (139 men, 25 women) and the incidence of mesothelioma (1998-2016) was estimated for 178 subjects (153 men, 25 women).

MAIN OUTCOMES MEASURES: mortality (Standardized Mortality Ratio: SMR) and hospitalization (Standardized Hospitalization Ratio: SHR) from specific diseases were analysed. Incidence (Standardized Incidence Ratio: SIR) of mesothelioma cases was detected, also. SMR (1986-2014), SHR (2001-2016) and SIR (1998-2016), with 95% Confidence Intervals, were computed with respect to the regional rates, with STATA11.

RESULTS: in the men cohort, mortality from lung (17 cases, SMR 2.83) and pleural cancers (5 cases, SMR 30) and from asbestosis (15 cases, SMR 1,930) was in excess. The risk of hospitalization was in excess, in both genders, from lung cancer (men: 6 cases, SHR 4.1; women: 2 cases, SHR 8.6) and asbestosis (men: 17 cases, SHR 1,304; women: 6 cases, SHR 2,455). The incidence of mesothelioma was in excess in men (5 cases, SIR 23.9); no female cases of mesothelioma were observed.

CONCLUSIONS: a high occurrence of asbestos-related diseases in the cohort, particularly among men, was observed. The excess of hospitalization from asbestosis and lung cancer was highlighted also in women. The prosecution of the on-going health surveillance plan is particularly appropriated.}, } @article {pmid32626907, year = {2021}, author = {Mezei, G and Chang, ET and Mowat, FS and Moolgavkar, SH}, title = {Comments on a recent case-control study of malignant mesothelioma of the pericardium and the tunica vaginalis testis.}, journal = {Scandinavian journal of work, environment & health}, volume = {47}, number = {1}, pages = {85-86}, pmid = {32626907}, issn = {1795-990X}, mesh = {*Asbestos/adverse effects ; Case-Control Studies ; Female ; Humans ; Italy ; Male ; *Mesothelioma/epidemiology ; *Mesothelioma, Malignant ; Middle Aged ; *Occupational Exposure ; Pericardium ; Testis ; }, abstract = {As the first case-control study of malignant mesothelioma of the pericardium and the tunica vaginalis testis (mTVT), the paper by Marinaccio et al (1) is potentially an important epidemiologic contribution. A careful review of the paper, however, raises a number of methodological issues. Any case-control study can be viewed as being nested within a conceptual cohort, with controls being sampled from the at-risk cohort as cases arise over time. This view of case-control studies leads to the concept of incidence-density sampling of controls (eg, 2, 3). For Marinaccio et al (1) this would mean that, as cases were registered over the study period, each would be matched to an individual control or set of controls of the same gender, age, and region of the country (since asbestos exposure varies by time and region [4]). For example, if a case were 50 years old in 1995, then any matched control should be close to age 50 in 1995 and of the same gender and from the same region as the case. Matching for age in this fashion automatically results in matching for year of birth, which is essential in this context because birth-cohort effects are determinants of asbestos exposure and mesothelioma incidence (eg, 5-8). If Marinaccio et al (1) used this scheme for age-matching, one would expect to see similar distributions of cases (table 1) and controls (table S3 in the supplemental material) by period of birth. Among males, however, the distributions of mesothelioma cases (whether pericardial or mTVT) and controls by period of birth are clearly different (P<0.001). Among females, the distributions of cases of pericardial mesothelioma and controls by birth year are less dissimilar (P≈0.05). Thus, the female cases of pericardial mesothelioma are better matched to controls on year of birth than are male cases of either mTVT or pericardial mesothelioma. We note also that the distributions of male and female controls by year of birth are distinctly different (P<0.002), whereas the birth-year distributions of cases of mesothelioma by site and gender are not (P≈0.8). In the Marinaccio et al (1) sensitivity analysis restricted to subjects born before 1950, the distributions of cases and controls by period of birth remain significantly different. Therefore, based on the reported evidence, cases and controls were not matched on birth cohort, thereby possibly biasing the results. Similarly, bias may result from the lack of matching on geographic region; while cases were registered from across Italy, controls were selected from only six regions. Although a sensitivity analysis restricted cases and controls to those from only the six regions, a comparison of tables S1 and S3 indicates that the regional distribution of controls is different from that of person-time observed; that is, the controls do not appear to be representative of the underlying population at risk by region. The second major issue of concern has to do with ascertainment of asbestos exposure. Information on exposure for the cases was presumably obtained at the time of registration. The two sets of controls, obtained from previously unpublished case-control studies, were interviewed during 2014-2015 and 2014-2016; that is, many years after the exposure for most cases was ascertained (1993-2015). Few other details of the control groups are provided, except that participation by one set of controls was <50%, raising additional concerns about selection bias. For details on the second set of controls, Marinaccio et al (1) reference a paper by Brandi et al (9). On review of that paper, however, we found no description of the control group, only references to three earlier papers. Marinaccio et al (1) present analyses only with both sets of controls combined; to evaluate potential sources of bias from the use of different sets of controls, they should also report results using each set of controls separately. The authors also did not detail their methods of exposure classification. For example, what does probable or possible exposure mean? The authors should at least present separate analyses of definite occupational exposure. Eighty cases of mTVT were registered, but only 68 were included in the analyses. Information on the 12 omitted cases (eg, age, year of birth, and region) would be helpful. Marinaccio et al (1) did not provide clear information on what occupations and/or industries they considered as exposed to asbestos. In an earlier study, Marinaccio et al (10) remarked on the absence of pericardial mesothelioma and mTVT in industries with the highest exposures to asbestos, saying, "[t]he absence of exposures in the shipbuilding, railway and asbestos-cement industries … for all the 67 pericardial and testicular cases is noteworthy but not easy to interpret." By contrast, Marinaccio et al (1) stated, "[t]he economic sectors more frequently associated with asbestos exposure were construction, steel mills, metal-working industry, textile industry and agriculture." The possibility of exposure in the "agriculture economic sector" was not mentioned in Marinaccio et al (10) and appears not to have been considered in previous epidemiologic studies in Italy. In general, epidemiologic studies indicate that farmers and agricultural workers are not at increased risk of developing mesothelioma (eg, 11-17). The fact that few, if any, cases of mTVT and pericardial mesothelioma occurred in industries traditionally associated with high asbestos exposure raises the possibility that the results of Marinaccio et al (1) are attributable to deficiencies in study design, very possibly bias in the selection of controls, and deficiencies in exposure assessment and classification as described above, leading to a spurious association of occupational exposure with mTVT and male pericardial mesothelioma. Conflict of interest This research has received no outside funding. All authors are employees of Exponent, Inc., an international scientific and engineering consulting company. All authors have worked as both consulting and testifying experts in litigation matters related to asbestos exposure and asbestos-related disease. References 1. Marinaccio A, Consonni D, Mensi C, Mirabelli D, Migliore E, Magnani C et al.; ReNaM Working Group. Association between asbestos exposure and pericardial and tunica vaginalis testis malignant mesothelioma: a case-control study and epidemiological remarks. Scand J Work Environ Health. 2020;46(6):609-617. https://doi.org/10.5271/sjweh.3895. 2. Rothman KJ, Greenland S, Lash TL. Modern Epidemiology. 2008; Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins. 3. Richardson DB. An incidence density sampling program for nested case-control analyses. Occup Environ Med 2004 Dec;61(12):e59. https://doi.org/10.1136/oem.2004.014472. 4. Marinaccio A, Binazzi A, Marzio DD, Scarselli A, Verardo M, Mirabelli D et al.; ReNaM Working Group. Pleural malignant mesothelioma epidemic: incidence, modalities of asbestos exposure and occupations involved from the Italian National Register. Int J Cancer 2012 May;130(9):2146-54. https://doi.org/10.1002/ijc.26229. 5. La Vecchia C, Decarli A, Peto J, Levi F, Tomei F, Negri E. An age, period and cohort analysis of pleural cancer mortality in Europe. Eur J Cancer Prev 2000 Jun;9(3):179-84. https://doi.org/10.1097/00008469-200006000-00005. 6. Price B, Ware A. Mesothelioma trends in the United States: an update based on Surveillance, Epidemiology, and End Results Program data for 1973 through 2003. Am J Epidemiol 2004 Jan;159(2):107-12. https://doi.org/10.1093/aje/kwh025. 7. Moolgavkar SH, Meza R, Turim J. Pleural and peritoneal mesotheliomas in SEER: age effects and temporal trends, 1973-2005. Cancer Causes Control 2009 Aug;20(6):935-44. https://doi.org/10.1007/s10552-009-9328-9. 8. Moolgavkar SH, Chang ET, Mezei G, Mowat FS. Chapter 3. Epidemiology of mesothelioma. In Testa JR. Asbestos and mesothelioma; 2017. pp. 43-72. Cham, Switzerland: Springer International Publishing. 9. Brandi G, Di Girolamo S, Farioli A, de Rosa F, Curti S, Pinna AD et al. Asbestos: a hidden player behind the cholangiocarcinoma increase? Findings from a case-control analysis. Cancer Causes Control 2013 May;24(5):911-8. https://doi.org/10.1007/s10552-013-0167-3. 10. Marinaccio A, Binazzi A, Di Marzio D, Scarselli A, Verardo M, Mirabelli D et al. Incidence of extrapleural malignant mesothelioma and asbestos exposure, from the Italian national register. Occup Environ Med 2010 Nov;67(11):760-5. https://doi.org/10.1136/oem.2009.051466. 11. Teschke K, Morgan MS, Checkoway H, Franklin G, Spinelli JJ, van Belle G et al. Mesothelioma surveillance to locate sources of exposure to asbestos. Can J Public Health 1997 May-Jun;88(3):163-8. https://doi.org/10.1007/BF03403881. 12. Bouchardy C, Schüler G, Minder C, Hotz P, Bousquet A, Levi F et al. Cancer risk by occupation and socioeconomic group among men--a study by the Association of Swiss Cancer Registries. Scand J Work Environ Health 2002;28(1 Suppl 1):1-88. 13. Hemminki K, Li X. Time trends and occupational risk factors for pleural mesothelioma in Sweden. J Occup Environ Med 2003a Apr;45(4):456-61. https://doi.org/10.1097/01.jom.0000058341.05741.7e. 14. Hemminki K, Li X. Time trends and occupational risk factors for peritoneal mesothelioma in Sweden. J Occup Environ Med 2003b Apr;45(4):451-5. https://doi.org/10.1097/01.jom.0000052960.59271.d4. 15. Pukkala E, Martinsen JI, Lynge E, Gunnarsdottir HK, Sparén P, Tryggvadottir L et al. Occupation and cancer - follow-up of 15 million people in five Nordic countries. Acta Oncol 2009;48(5):646-790. https://doi.org/10.1080/02841860902913546. 16. Rolland P, Gramond C, Berron H, Ducamp S, Imbernon E, Goldberg M et al. Mesotheliome pleural: Professions et secteurs d'activite a risque chez les hommes [Pleural mesothelioma: Professions and occupational areas at risk among humans]. 2005; Institut de Veille Sanitaire, Departement Sante Travai, Saint-Maurice, France. 17. Rolland P, Gramond C, Lacourt A, Astoul P, Chamming's S, Ducamp S et al. PNSM Study Group. Occupations and industries in France at high risk for pleural mesothelioma: A population-based case-control study (1998-2002). Am J Ind Med 2010 Dec;53(12):1207-19. https://doi.org/10.1002/ajim.20895.}, } @article {pmid32624414, year = {2020}, author = {Paajanen, J and Laaksonen, S and Ilonen, I and Vehmas, T and Mäyränpää, MI and Sutinen, E and Kettunen, E and Salo, JA and Räsänen, J and Wolff, H and Myllärniemi, M}, title = {Clinical Features in Patients With Malignant Pleural Mesothelioma With 5-Year Survival and Evaluation of Original Diagnoses.}, journal = {Clinical lung cancer}, volume = {21}, number = {6}, pages = {e633-e639}, doi = {10.1016/j.cllc.2020.05.020}, pmid = {32624414}, issn = {1938-0690}, mesh = {Aged ; Case-Control Studies ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Male ; Mesothelioma, Malignant/*mortality/pathology/therapy ; Middle Aged ; Pleural Neoplasms/*mortality/pathology/therapy ; Prognosis ; Registries/*statistics & numerical data ; Retrospective Studies ; Survival Rate ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is a fatal malignancy strongly associated with previous asbestos exposure. Overall survival remains dismal, partly owing to poor response to available treatment. The aims of this study were to evaluate diagnostic accuracy in a group of patients with MPM with an unusually long survival time and to assess the factors related to this prolonged survival.

MATERIALS AND METHODS: Forty-three patients with overall survival exceeding 5 years were accepted to the long-term survivor (LTS) group, and these patients were compared with 84 patients with epithelial MPM. Data were collected from various national registries and electronic medical records. In addition, all available histopathologic diagnostic samples and computed tomography studies were re-evaluated by experienced specialists.

RESULTS: Our study showed a good diagnostic accuracy, with only 1 (0.5%) patient having an incorrect MPM diagnosis. Two (0.9%) localized malignant mesotheliomas and 2 (0.9%) well-differentiated papillary mesotheliomas were also found. LTS patients were younger, more frequently female, had a better performance status at time of diagnosis, and had less evidence of prior asbestos exposure. In multivariate analysis, we showed tumor size, Eastern Cooperative Oncology Group performance status, and first-line treatment (both surgery and chemotherapy) to be associated with survival time.

CONCLUSION: We confirmed the diagnosis of MPM in an overwhelming majority of patients in the LTS group. An epithelial subtype of MPM behaving clinically more indolently seems to exist, but further tumor and genetic characterization is needed. The prolonged survival time is most likely explained by a combination of tumor-, patient-, and treatment-related factors.}, } @article {pmid32604114, year = {2020}, author = {Xu, T and Hu, J and Zhang, X and Cao, J and Chen, Y}, title = {A Case of Localized Malignant Peritoneal Mesothelioma Evaluated by 18F-FDG PET/CT.}, journal = {Clinical nuclear medicine}, volume = {45}, number = {11}, pages = {890-891}, doi = {10.1097/RLU.0000000000003158}, pmid = {32604114}, issn = {1536-0229}, mesh = {Aged ; Female ; *Fluorodeoxyglucose F18 ; Humans ; Lung Neoplasms/*diagnostic imaging/pathology ; Mesothelioma/*diagnostic imaging/pathology ; Mesothelioma, Malignant ; Peritoneal Neoplasms/*diagnostic imaging/pathology ; *Positron Emission Tomography Computed Tomography ; Prognosis ; }, abstract = {Localized malignant mesothelioma is rare. The prognosis is generally more favorable for this condition than for diffuse malignant mesothelioma. An elderly woman recently complained of abdominal pain, fever, and weight loss. She had no history of asbestos exposure. Her serum CEA level was elevated. Plain CT revealed a mass under the left diaphragm, with liquefaction and necrosis. A contrast-enhanced scan showed circular enhancement of the mass. A subsequent biopsy of the mass revealed a poorly differentiated carcinoma. PET/CT showed a significant FDG-avid subphrenic mass without any indications of metastasis. Postoperative pathological and immunohistochemical examination confirmed a case of malignant mesothelioma.}, } @article {pmid32602389, year = {2022}, author = {Boice, JD and Cohen, SS and Mumma, MT and Chen, H and Golden, AP and Beck, HL and Till, JE}, title = {Mortality among U.S. military participants at eight aboveground nuclear weapons test series.}, journal = {International journal of radiation biology}, volume = {98}, number = {4}, pages = {679-700}, doi = {10.1080/09553002.2020.1787543}, pmid = {32602389}, issn = {1362-3095}, support = {U01 CA137026/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Leukemia, Lymphocytic, Chronic, B-Cell ; Male ; *Mesothelioma ; *Myocardial Ischemia ; *Nuclear Weapons ; Radiometry ; }, abstract = {BACKGROUND: Approximately 235,000 military personnel participated at one of 230 U.S. atmospheric nuclear weapons tests from 1945 through 1962. At the Nevada Test Site (NTS), the atomic veterans participated in military maneuvers, observed nuclear weapons tests, or provided technical support. At the Pacific Proving Ground (PPG), they served aboard ships or were stationed on islands during or after nuclear weapons tests.

MATERIAL AND METHODS: Participants at seven test series, previously studied with high-quality dosimetry and personnel records, and the first test at TRINITY formed the cohort of 114,270 male military participants traced for vital status from 1945 through 2010. Dose reconstructions were based on Nuclear Test Personnel Review records, Department of Defense. Standardized mortality ratios (SMR) and Cox and Poisson regression models were used in the analysis.

RESULTS: Most atomic veterans were enlisted men, served in the Navy at the PPG, and were born before 1930. Vital status was determined for 96.8% of the veterans; 60% had died. Enlisted men had significantly high all-causes mortality SMR (1.06); officers had significantly low all-causes mortality SMR (0.71). The pattern of risk over time showed a diminution of the 'healthy soldier effect': the all-causes mortality SMR after 50 years of follow-up was 1.00. The healthy soldier effect for all cancers also diminished over time. The all-cancer SMR was significantly high after 50 years (SMR 1.10) primarily from smoking-related cancers, attributed in part to the availability of cigarettes in military rations. The highest SMR was for mesothelioma (SMR 1.56) which was correlated with asbestos exposure in naval ships. Prostate cancer was significantly high (SMR 1.13). Ischemic heart disease was significantly low (SMR 0.84). Estimated mean doses varied by organ were low; e.g., the mean red bone marrow dose was 6 mGy (maximum 108 mGy). Internal cohort dose-response analyses provided no evidence for increasing trends with radiation dose for leukemia (excluding chronic lymphocytic leukemia (CLL)) [ERR (95% CI) per 100 mGy -0.37 (-1.08, 0.33); n = 710], CLL, myelodysplastic syndrome, multiple myeloma, ischemic heart disease, or cancers of the lung, prostate, breast, and brain.

CONCLUSION: No statistically significant radiation associations were observed among 114,270 nuclear weapons test participants followed for up to 65 years. The 95% confidence limits were narrow and excluded mortality risks per unit dose that are two to four times higher than those reported in other investigations. Significantly elevated SMRs were seen for mesothelioma and asbestosis, attributed to asbestos exposure aboard ships.}, } @article {pmid32600665, year = {2020}, author = {Marinaccio, A and Gariazzo, C and Di Marzio, D and Iavicoli, S and , }, title = {Predictors of filing claims and receiving compensation in malignant mesothelioma patients.}, journal = {Health policy (Amsterdam, Netherlands)}, volume = {124}, number = {9}, pages = {1032-1040}, doi = {10.1016/j.healthpol.2020.06.005}, pmid = {32600665}, issn = {1872-6054}, mesh = {*Asbestos/toxicity ; Filing ; Humans ; Italy ; *Mesothelioma ; *Mesothelioma, Malignant ; *Occupational Exposure ; }, abstract = {Although the predominant occupation origin of mesothelioma is well known, determinant factors involved in filing compensation are scarcely investigated. A linkage between incident mesothelioma cases collected by Italian mesothelioma register (ReNaM) and compensation claims and assignment by Italian national insurance Institute (INAIL) has been conducted for cases diagnosed in the period 2010-2015 and occupational exposure to asbestos. Logistic regression models and decision tree models have been used to identify demographic, diagnostic and anamnestic factors significant for filing and receiving compensation. We have included in the analyses 5019 mesothelioma cases, and among them, 3321 (66.2 %) were found in INAIL archives as mesothelioma cases who fil claims for compensation. The modalities of asbestos exposure, sector of working activities and job type are crucial factors. Furthermore, gender, age at diagnosis, area of residence have been found to be significant predictors of probability to fil claims. Relative risks to fil claims were obtained for the above determinants and conditions to maximize the probability to obtain compensation identified. Our findings demonstrate that there is a need to enforce policies for improving awareness of the occupational origin for mesothelioma cases. Stakeholders, occupational health and safety institutions can play an important role for improving the sensitization regarding the rights of compensation benefits, ensuring the equity and the effectiveness of insurance, welfare and public health systems.}, } @article {pmid32596966, year = {2020}, author = {Sherborne, V and Seymour, J and Taylor, B and Tod, A}, title = {What are the psychological effects of mesothelioma on patients and their carers? A scoping review.}, journal = {Psycho-oncology}, volume = {29}, number = {10}, pages = {1464-1473}, doi = {10.1002/pon.5454}, pmid = {32596966}, issn = {1099-1611}, mesh = {*Adaptation, Psychological ; Caregivers/*psychology ; Emotions ; Female ; Humans ; Male ; Mental Health ; Mesothelioma, Malignant/*psychology ; Palliative Care ; *Psychological Distress ; Quality of Life/*psychology ; Stress, Psychological ; Uncertainty ; }, abstract = {OBJECTIVE: Despite recent advances in research, malignant mesothelioma remains an incurable and devastating disease, typically bringing shock and emotional distress to patients and carers. Little research has addressed the psychological impact on either group. This scoping review examines the current state of evidence on the psychological effects of mesothelioma on patients and carers, and identifies areas for further research.

METHODS: We searched PubMed, PsychINFO, CINAHL, the Cochrane Library and Web of Science for English-language peer-reviewed research articles published 1981 to 2019 reporting studies focussing on the psychological effects of mesothelioma on patients and carers. Following data extraction and quality appraisal, reflexive thematic analysis was used to identify themes.

RESULTS: Seventeen articles met the inclusion criteria. Carers' experiences were generally amalgamated with patients'. Three themes were developed. The Passing of Time included the importance of timing of interventions; delays in the medical journey; awareness of different time-phases in mesothelioma; and uncertainty/certainty. Dealing with Difficult Feelings reflected ubiquitous negative emotions, feelings about identity and states of being and associated coping strategies. Craving Good Communication covered issues related to sharing of information and to positive/negative aspects of communication.

CONCLUSIONS: Though limited, the evidence indicates that mesothelioma, with its high symptom-burden, incurability, rarity and asbestos-related causation, leads to complex and inter-relating psychological effects on patients and carers. These effects are both negative and positive. The sparse literature gives a partial picture and demonstrates an urgent need for more nuanced research. Studies exploring the experiences of specific groups are recommended, with particular attention required to carers.}, } @article {pmid32583627, year = {2020}, author = {Shinozaki-Ushiku, A and Kohsaka, S and Kage, H and Oda, K and Miyagawa, K and Nakajima, J and Aburatani, H and Mano, H and Ushiku, T}, title = {Genomic profiling of multiple primary cancers including synchronous lung adenocarcinoma and bilateral malignant mesotheliomas: Identification of a novel BAP1 germline variant.}, journal = {Pathology international}, volume = {70}, number = {10}, pages = {775-780}, doi = {10.1111/pin.12977}, pmid = {32583627}, issn = {1440-1827}, support = {JP19kk0205016//Japan Agency for Medical Research and Development/ ; //Sysmex Corporation/ ; }, mesh = {Adenocarcinoma of Lung/complications/*diagnosis/genetics/pathology ; Aged ; Genetic Predisposition to Disease ; Genomics ; Germ-Line Mutation ; Humans ; Immunohistochemistry ; Lung Neoplasms/complications/*diagnosis/genetics/pathology ; Male ; Mesothelioma, Malignant/complications/*diagnosis/genetics/pathology ; Neoplasms, Multiple Primary ; Peritoneal Neoplasms/complications/*diagnosis/genetics/pathology ; Tumor Suppressor Proteins/*genetics/metabolism ; Ubiquitin Thiolesterase/*genetics/metabolism ; Urinary Bladder Neoplasms/complications/*diagnosis/genetics/pathology ; }, abstract = {We report a case with a rare combination of synchronous lung adenocarcinoma and bilateral malignant pleural mesotheliomas in a 70-year-old male without asbestos exposure. He metachronously developed peritoneal malignant mesothelioma, intrahepatic cholangiocarcinoma, urothelial carcinoma of the bladder and prostatic adenocarcinoma. Immunohistochemistry revealed complete loss of BAP1 expression in all seven lesions. Targeted next generation sequencing using Todai OncoPanel identified a novel germline variant (c.1565_1566del, p.P522Rfs*14) of BAP1. Additionally, different nonsynonymous somatic mutations of BAP1 were identified in four lesions including lung adenocarcinoma, malignant pleural and peritoneal mesotheliomas, and bladder cancer. The remaining two lesions had different somatic mutations in genes other than BAP1. Multiple BAP1-deficient cancers that developed in a single patient suggest the newly identified germline variant of BAP1 gene to be pathogenic and this case expands the clinical spectrum of BAP1-tumor predisposition syndrome. Screening for BAP1 status is highly recommended in cases with a similar combination of cancers.}, } @article {pmid32581164, year = {2020}, author = {Ide, Y and Yuki, T and Taooka, Y and Higashi, Y and Tachiyama, Y}, title = {Malignant Peritoneal Mesothelioma Presenting with Polymyalgia Rheumatica-like Syndrome.}, journal = {Internal medicine (Tokyo, Japan)}, volume = {59}, number = {20}, pages = {2629-2632}, pmid = {32581164}, issn = {1349-7235}, mesh = {Adult ; Diagnosis, Differential ; Giant Cell Arteritis/diagnosis ; Glucocorticoids/therapeutic use ; Humans ; Male ; Mesothelioma, Malignant/*complications ; Paraneoplastic Syndromes/*complications/*diagnosis ; Peritoneal Neoplasms/*complications ; Polymyalgia Rheumatica/diagnosis ; }, abstract = {A 30-year-old man was admitted to our hospital because of pain in his proximal extremities. The pain mimicked polymyalgia rheumatica (PMR) and it temporarily improved by a low dose of glucocorticoids, but his symptoms relapsed many times. After six years of glucocorticoid treatment, he developed abdominal pain and ascites, for which he was diagnosed with malignant peritoneal mesothelioma (MPM). His PMR-like symptoms improved with cytoreductive surgery and chemotherapy for MPM. Finally, we diagnosed this PMR-like syndrome to be paraneoplastic syndrome with MPM. Although cases of MPM complicated by PMR-like syndrome are rare, MPM should be taken into account in the differential diagnosis.}, } @article {pmid32581053, year = {2020}, author = {Blondy, T and d'Almeida, SM and Briolay, T and Tabiasco, J and Meiller, C and Chéné, AL and Cellerin, L and Deshayes, S and Delneste, Y and Fonteneau, JF and Boisgerault, N and Bennouna, J and Grégoire, M and Jean, D and Blanquart, C}, title = {Involvement of the M-CSF/IL-34/CSF-1R pathway in malignant pleural mesothelioma.}, journal = {Journal for immunotherapy of cancer}, volume = {8}, number = {1}, pages = {}, pmid = {32581053}, issn = {2051-1426}, mesh = {Aged ; Biomarkers, Tumor/genetics/*metabolism ; CD8-Positive T-Lymphocytes/immunology/metabolism/pathology ; Cytokines/metabolism ; Female ; Follow-Up Studies ; Humans ; Interleukins/genetics/*metabolism ; Macrophage Colony-Stimulating Factor/genetics/*metabolism ; Macrophages/immunology/metabolism/pathology ; Male ; Mesothelioma, Malignant/genetics/immunology/metabolism/*pathology ; Monocytes/immunology/metabolism/pathology ; Pleural Effusion/immunology/metabolism/*pathology ; Pleural Neoplasms/genetics/immunology/metabolism/*pathology ; Prognosis ; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/genetics/*metabolism ; Survival Rate ; T-Lymphocytes, Cytotoxic/immunology ; Tumor Microenvironment/immunology ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer related to asbestos exposure. The tumor microenvironment content, particularly the presence of macrophages, was described as crucial for the development of the disease. This work aimed at studying the involvement of the M-CSF (CSF-1)/IL-34/CSF-1R pathway in the formation of macrophages in MPM, using samples from patients.

METHODS: Pleural effusions (PEs), frozen tumors, primary MPM cells and MPM cell lines used in this study belong to biocollections associated with clinical databases. Cytokine expressions were studied using real-time PCR and ELISA. The Cancer Genome Atlas database was used to confirm our results on an independent cohort. An original three-dimensional (3D) coculture model including MPM cells, monocytes from healthy donors and a tumor antigen-specific cytotoxic CD8 T cell clone was used.

RESULTS: We observed that high interleukin (IL)-34 levels in PE were significantly associated with a shorter survival of patients. In tumors, expression of CSF1 was correlated with 'M2-like macrophages' markers, whereas this was not the case with IL34 expression, suggesting two distinct modes of action of these cytokines. Expression of IL34 was higher in MPM cells compared with primary mesothelial cells. Particularly, high expression of IL34 was observed in MPM cells with an alteration of CDKN2A. Finally, using 3D coculture model, we demonstrated the direct involvement of MPM cells in the formation of immunosuppressive macrophages, through activation of the colony stimulating factor-1 receptor (CSF1-R) pathway, causing the inhibition of cytotoxicity of tumor antigen-specific CD8[+] T cells.

CONCLUSIONS: The M-CSF/IL-34/CSF-1R pathway seems strongly implicated in MPM and could constitute a therapeutic target to act on immunosuppression and to support immunotherapeutic strategies.}, } @article {pmid32571118, year = {2020}, author = {Ierardi, AM and Marsh, GM}, title = {Absence of mesothelioma risk maintained in an expanded international cohort of cosmetic talc miners and millers.}, journal = {Inhalation toxicology}, volume = {32}, number = {6}, pages = {257-264}, doi = {10.1080/08958378.2020.1781304}, pmid = {32571118}, issn = {1091-7691}, mesh = {Cohort Studies ; Cosmetics ; Europe/epidemiology ; Extraction and Processing Industry ; Humans ; Mesothelioma/*epidemiology ; Occupational Diseases/*epidemiology ; *Occupational Exposure ; Pleural Neoplasms/*epidemiology ; Risk Factors ; *Talc ; Vermont/epidemiology ; }, abstract = {Objectives: Based on novel information for the Vermont cosmetic talc miner/miller cohort, including a reported case of mesothelioma, we sought to update our prior pooled statistical power analyses of mesothelioma incidence among European cosmetic talc miners/millers. With the inclusion of the Vermont cohort, we expanded our pooled analysis by 17,170 person-years of observation.Methods: Cosmetic talc miner/miller cohort studies conducted in Italy, Norway, France, Austria, and Vermont were pooled. The expected numbers of mesothelioma cases for each cohort as reported in these studies were used. Our statistical power analysis was based on an a priori one-sided significance level of 0.05 and Poisson distribution probabilities.Results: A total of 130,514 person-years of observation was generated across the five cohorts. One case of mesothelioma was observed (in the Vermont cohort), while approximately 3.34 cases (a mid-value estimate) were expected overall. Thus, we found that the pooled cohorts had 59% and 78% power to detect a 2.5-fold or greater and a 3.0-fold or greater increase in mesothelioma, respectively. The work history characteristics of the one mesothelioma case, which included mention of prior asbestos exposure on the case's death certificate, do not support a causal link with cosmetic talc exposure.Conclusions: Despite the recent finding of one case of mesothelioma in the Vermont cohort (a case unlikely related to talc exposure), we continue to conclude that the epidemiological evidence from the cosmetic talc miner/miller cohort studies does not support the hypothesis that cosmetic talc exposures are associated with an increased risk of pleural mesothelioma.}, } @article {pmid32560575, year = {2020}, author = {Panou, V and Røe, OD}, title = {Inherited Genetic Mutations and Polymorphisms in Malignant Mesothelioma: A Comprehensive Review.}, journal = {International journal of molecular sciences}, volume = {21}, number = {12}, pages = {}, pmid = {32560575}, issn = {1422-0067}, mesh = {Alleles ; Animals ; DNA Repair ; *Genetic Association Studies ; *Genetic Predisposition to Disease ; Genetic Variation ; *Germ-Line Mutation ; Humans ; Mesothelioma, Malignant/*genetics ; Pedigree ; *Polymorphism, Single Nucleotide ; }, abstract = {Malignant mesothelioma (MM) is mainly caused by air-born asbestos but genetic susceptibility is also suspected to be a risk factor. Recent studies suggest an increasing number of candidate genes that may predispose to MM besides the well-characterized BRCA1-associated protein-1 gene. The aim of this review is to summarize the most important studies on germline mutations for MM. A total of 860 publications were retrieved from Scopus, PubMed and Web of Science, of which 81 met the inclusion criteria and were consider for this review. More than 50% of the genes that are reported to predispose to MM are involved in DNA repair mechanisms, and the majority of them have a role in the homologous recombination pathway. Genetic alterations in tumor suppressor genes involved in chromatin, transcription and hypoxia regulation have also been described. Furthermore, we identified several single nucleotide polymorphisms (SNPs) that may promote MM tumorigenesis as a result of an asbestos-gene interaction, including SNPs in DNA repair, carcinogen detoxification and other genes previously associated with other malignancies. The identification of inherited mutations for MM and an understanding of the underlying pathways may allow early detection and prevention of malignancies in high-risk individuals and pave the way for targeted therapies.}, } @article {pmid32560553, year = {2020}, author = {Bonafede, M and Granieri, A and Binazzi, A and Mensi, C and Grosso, F and Santoro, G and Franzoi, IG and Marinaccio, A and Guglielmucci, F}, title = {Psychological Distress after a Diagnosis of Malignant Mesothelioma in a Group of Patients and Caregivers at the National Priority Contaminated Site of Casale Monferrato.}, journal = {International journal of environmental research and public health}, volume = {17}, number = {12}, pages = {}, pmid = {32560553}, issn = {1660-4601}, mesh = {Adaptation, Psychological ; Adult ; Aged ; Asbestos/adverse effects ; Asbestosis/diagnosis/epidemiology/etiology/psychology ; Carcinogens ; Caregivers/*psychology/statistics & numerical data ; Cross-Sectional Studies ; Depression/epidemiology/etiology/psychology ; Environmental Exposure/statistics & numerical data ; Female ; Humans ; Italy/epidemiology ; Male ; Mesothelioma/diagnosis/*epidemiology/etiology/*psychology ; Middle Aged ; Occupational Diseases/diagnosis/*epidemiology/etiology/*psychology ; *Psychological Distress ; Registries/statistics & numerical data ; Risk Factors ; Stress Disorders, Post-Traumatic/epidemiology/etiology/psychology ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Patients of malignant mesothelioma (MM) and their caregivers face significant physical and psychological challenges. The purpose of the present study is to examine the emotional impact after the diagnosis of MM in a group of patients and familial caregivers in a National Priority Contaminated Site (NPCS).

METHODS: A sample of 108 patients and 94 caregivers received a sociodemographic/clinical questionnaire, the Beck Depression Inventory II, the Davidson Trauma Scale, the Coping Orientation to the Problems Experienced-New Italian Version, and the Defense style questionnaire. The risk of depressive and post-traumatic stress disorder (PTSD) symptoms in relation to the strategies of coping and defense mechanisms was estimated in patients and caregivers separately by logistic regression models.

RESULTS: For patients, a high risk of depression was associated with high usage of Defense Style Questionnaire (DSQ) Isolation (OR: 53.33; 95% CI: 3.22-882.30; p = 0.01) and DSQ Somatization (OR: 16.97; 95% CI: 1.04-275.90; p = 0.05). Other significant risks emerged for some coping strategies and some defenses regarding both depression and trauma in patients and caregivers.

CONCLUSIONS: This research suggests that for both patients and caregivers unconscious adaptive processes have a central role in dealing with overwhelming feelings related to the disease.}, } @article {pmid32553000, year = {2020}, author = {Musk, AW and de Klerk, N and Reid, A and Hui, J and Franklin, P and Brims, F}, title = {Asbestos-related diseases.}, journal = {The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease}, volume = {24}, number = {6}, pages = {562-567}, doi = {10.5588/ijtld.19.0645}, pmid = {32553000}, issn = {1815-7920}, mesh = {*Asbestos/toxicity ; *Asbestosis/diagnostic imaging/epidemiology ; Humans ; *Lung Neoplasms/epidemiology/etiology ; *Mesothelioma/epidemiology/etiology/therapy ; Pleura ; }, abstract = {Knowledge of asbestos-related diseases has been accumulating for over one hundred years as the industrial value of asbestos was recognised for the strength of its fibres and their resistance to destruction, resulting in increasing production and use until the multiple health effects have become apparent. Deposition in the lung parenchyma results in an inflammatory/progressively fibrotic response, with impaired gas exchange and reduced lung compliance ('asbestosis'), causing progressive dyspnoea and respiratory failure for which only palliation is indicated, although anti-fibrotic agents used for idiopathic usual interstitial pneumonitis remain to be evaluated. Benign pleural effusion, diffuse pleural fibrosis (occasionally with associated rolled atelectasis) and pleural plaques are the non-malignant pleural diseases that result from fibres reaching the pleura. But the main issues that led to the ban on asbestos in industry are those of malignancy: lung cancer, malignant mesothelioma (MM) of the pleura and MM of the peritoneum. Bronchogenic carcinoma risk from asbestos exposure is dose-dependent and multiplies the risk attributable to tobacco smoking. The principles of treatment are as for all cases of lung cancer. Low-dose computed tomography screening of exposed people can detect early-stage, non-small cell cancers, with improved survival. The amphibole varieties of asbestos are much more potent causes of MM than chrysotile, and the risk increases exponentially for 40-50 years following first exposure. As MM is non-resectable and poorly responsive to chemotherapy and radiotherapy, curative treatment is not possible and screening not justified.}, } @article {pmid32549902, year = {2020}, author = {Frank, AL}, title = {Global use of asbestos - legitimate and illegitimate issues.}, journal = {Journal of occupational medicine and toxicology (London, England)}, volume = {15}, number = {}, pages = {16}, pmid = {32549902}, issn = {1745-6673}, abstract = {BACKGROUND: Exposure to asbestos causes non-malignant and malignant diseases including asbestosis, lung cancer, and mesothelioma. The modern history of such diseases goes back more than a century.

MAIN TEXT: While much is known about the ability of asbestos to cause disease, the carcinogenic mechanism is not yet understood. Continuing legitimate scientific questions include such issues as potential differential toxicity and carcinogenicity of different fiber types. Illegitimate issues include the supposed "safe" use of asbestos, and the chrysotile hypothesis.

CONCLUSION: Asbestos disease issues are highly politicized and vested economic interests perpetuate false issues regarding the hazards of asbestos.}, } @article {pmid32549782, year = {2020}, author = {Franko, A and Goricar, K and Kovac, V and Dodic-Fikfak, M and Dolzan, V}, title = {NLRP3 and CARD8 polymorphisms influence risk for asbestos-related diseases.}, journal = {Journal of medical biochemistry}, volume = {39}, number = {1}, pages = {91-99}, pmid = {32549782}, issn = {1452-8258}, abstract = {BACKGROUND: This study aimed to investigate the association between NLRP3 rs35829419 and CARD8 rs2043211 polymorphisms and the risk of developing pleural plaques, asbestosis, and malignant mesothelioma (MM), and to study the influence of the interactions between polymorphisms and asbestos exposure on the risk of developing these diseases.

METHODS: The case-control study included 416 subjects with pleural plaques, 160 patients with asbestosis, 154 subjects with MM and 149 subjects with no asbestos disease. The NLRP3 rs35829419 and CARD8 rs2043211 polymorphisms were determined using real-time PCR-based methods. In the statistical analysis, standard descriptive statistics was followed by univariate and multivariate logistic regression modelling.

RESULTS: Asbestos exposure (medium and high vs low) was associated with the risk for each studied asbestos-related disease. An increased risk of pleural plaques was found for CARD8 rs2043211 at + TT genotypes (OR = 1.48, 95% CI 1.01-2.16, p = 0.042). When the analysis was performed for MM patients as cases, and pleural plaques patients as controls, a decreased MM risk was observed for carriers of CARD8 rs2043211 TT genotype (OR = 0.52, 95% CI 0.27-1.00, p = 0.049). The interactions between NLRP3 rs35829419 and CARD8 rs2043211 genotypes did not influence the risk of any asbestos-related disease. However, when testing interactions with asbestos exposure, a decreased risk of asbestosis was found for NLRP3 CA+AA genotypes (OR = 0.09, 95% CI 0.01-0.60, p = 0.014).

CONCLUSIONS: The results of our study suggest that NLRP3 and CARD8 polymorphisms could affect the risk of asbestos-related diseases.}, } @article {pmid32535843, year = {2020}, author = {Shibata, R and Ozaki, T and Tada, K and Aoyama, T and Watanabe, M and Himuro, N and Takahashi, K and Ito, K and Yasuno, T and Miyake, K and Masutani, K and Uesugi, N and Nabeshima, K and Nakashima, H}, title = {Secondary renal amyloidosis associated with asbestos-related pleuropulmonary diseases.}, journal = {CEN case reports}, volume = {9}, number = {4}, pages = {385-391}, pmid = {32535843}, issn = {2192-4449}, mesh = {Adult ; Aged ; Amyloidosis/*complications/pathology ; Angiotensin Receptor Antagonists/therapeutic use ; Asbestos/*adverse effects ; Asian People/ethnology ; Biopsy ; Female ; Humans ; Kidney/diagnostic imaging/pathology ; Male ; Middle Aged ; Nephrotic Syndrome/*diagnosis/drug therapy/etiology ; Occupational Exposure ; Pleura/pathology ; Pleural Diseases/complications/pathology ; Pleural Effusion/diagnosis/etiology ; Tomography, X-Ray Computed/methods ; }, abstract = {Here, we present a 67-year-old Japanese man who developed insidious-onset nephrotic syndrome. He had a history of occupational asbestos exposure for about 8 years during his 30s, and was found to have pleural effusion 3 years before his present illness. At that time, repeated cytology testing of his pleural effusion found no malignant cells, and pleural biopsy found fibrous pleuritis without evidence of malignant mesothelioma. Percutaneous kidney biopsy found massive deposits of AA-type amyloid in the glomeruli, small arteries, and medulla. Computed tomography showed a calcified mass in the right lower lung that was positive for [67]Ga uptake, but transbronchial lung biopsy and bronchoalveolar lavage found no evidence of malignancy. He was diagnosed with rounded atelectasis and diffuse pleural thickening. As these benign asbestos-related diseases have no standard treatment, we administered low-dose angiotensin II receptor blocker to preserve kidney function. Unfortunately, his nephrotic syndrome persists, with progressive chronic kidney failure. Kidney involvement in patients with asbestos-related disease is rare. To our knowledge, this is the first case to present with secondary amyloidosis. Kidney biopsy should be considered for patients with existing asbestos-related pleuropulmonary diseases who have urinary abnormalities or renal dysfunction, to clarify the incidence and pathophysiology of renal manifestations.}, } @article {pmid32530527, year = {2020}, author = {Horio, D and Minami, T and Kitai, H and Ishigaki, H and Higashiguchi, Y and Kondo, N and Hirota, S and Kitajima, K and Nakajima, Y and Koda, Y and Fujimoto, E and Negi, Y and Niki, M and Kanemura, S and Shibata, E and Mikami, K and Takahashi, R and Yokoi, T and Kuribayashi, K and Kijima, T}, title = {Tumor-associated macrophage-derived inflammatory cytokine enhances malignant potential of malignant pleural mesothelioma.}, journal = {Cancer science}, volume = {111}, number = {8}, pages = {2895-2906}, pmid = {32530527}, issn = {1349-7006}, support = {18K08161//Japan Society for the Promotion of Science/ ; 18K15962//Japan Society for the Promotion of Science/ ; 18K15963//Japan Society for the Promotion of Science/ ; 20K08555//Japan Society for the Promotion of Science/ ; }, mesh = {Aged ; Antineoplastic Combined Chemotherapy Protocols/pharmacology/therapeutic use ; Asbestos/toxicity ; Biopsy ; Cell Line, Tumor ; Cisplatin/pharmacology/therapeutic use ; Female ; Humans ; Inflammasomes/metabolism ; Interleukin-1beta/*metabolism ; Macrophages/drug effects/*metabolism ; Male ; Mesothelioma, Malignant/chemically induced/drug therapy/mortality/*pathology ; Middle Aged ; Pemetrexed/pharmacology/therapeutic use ; Pleura/*pathology ; Receptors, Interleukin-1 Type I/*metabolism ; Spheroids, Cellular ; Tumor Microenvironment/drug effects ; Up-Regulation ; }, abstract = {Malignant pleural mesothelioma (MPM) is an asbestos-related aggressive malignant neoplasm. Due to the difficulty of achieving curative surgical resection in most patients with MPM, a combination chemotherapy of cisplatin and pemetrexed has been the only approved regimen proven to improve the prognosis of MPM. However, the median overall survival time is at most 12 mo even with this regimen. There has been therefore a pressing need to develop a novel chemotherapeutic strategy to bring about a better outcome for MPM. We found that expression of interleukin-1 receptor (IL-1R) was upregulated in MPM cells compared with normal mesothelial cells. We also investigated the biological significance of the interaction between pro-inflammatory cytokine IL-1β and the IL-1R in MPM cells. Stimulation by IL-1β promoted MPM cells to form spheroids along with upregulating a cancer stem cell marker CD26. We also identified tumor-associated macrophages (TAMs) as the major source of IL-1β in the MPM microenvironment. Both high mobility group box 1 derived from MPM cells and the asbestos-activated inflammasome in TAMs induced the production of IL-1β, which resulted in enhancement of the malignant potential of MPM. We further performed immunohistochemical analysis using clinical MPM samples obtained from patients who were treated with the combination of platinum plus pemetrexed, and found that the overexpression of IL-1R tended to correlate with poor overall survival. In conclusion, the interaction between MPM cells and TAMs through a IL-1β/IL-1R signal could be a promising candidate as the target for novel treatment of MPM (Hyogo College of Medicine clinical trial registration number: 2973).}, } @article {pmid32528683, year = {2020}, author = {Amore, D and Massa, S and Caterino, U and Casazza, D and Palma, A and Curcio, C}, title = {Mediastinal malignant mesothelioma discovered in a patient with dysphagia.}, journal = {Respirology case reports}, volume = {8}, number = {6}, pages = {e00592}, pmid = {32528683}, issn = {2051-3380}, abstract = {A mediastinal mass in patients with a history of asbestos exposure should raise the suspicion of malignant mesothelioma.}, } @article {pmid32526494, year = {2020}, author = {Catelan, D and Consonni, D and Biggeri, A and Dallari, B and Pesatori, AC and Riboldi, L and Mensi, C}, title = {Estimate of environmental and occupational components in the spatial distribution of malignant mesothelioma incidence in Lombardy (Italy).}, journal = {Environmental research}, volume = {188}, number = {}, pages = {109691}, doi = {10.1016/j.envres.2020.109691}, pmid = {32526494}, issn = {1096-0953}, mesh = {*Asbestos/toxicity ; Bayes Theorem ; Environmental Exposure ; Female ; Humans ; Incidence ; Italy/epidemiology ; Male ; *Mesothelioma/chemically induced/epidemiology ; *Occupational Exposure ; Registries ; }, abstract = {INTRODUCTION: Measuring and mapping the occurrence of malignant mesothelioma (MM) is a useful means to monitor the impact of past asbestos exposure and possibly identify previously unknown sources of asbestos exposure.

OBJECTIVE: Our goal is to decompose the observed spatial pattern of incidence of MM in the Lombardy region (Italy) in gender-specific components linked to occupational exposure and a shared component linked to environmental exposure.

MATERIALS AND METHODS: We selected from the Lombardy Region Mesothelioma Registry (RML) all incident cases of MM (pleura, peritoneum, pericardium, and tunica vaginalis testis) with first diagnosis in the period 2000-2016. We mapped at municipality level crude incidence rates and smoothed rates using the Besag York and Mollié model separately for men and women. We then decomposed the spatial pattern of MM in gender-specific occupational components and a shared environmental component using a multivariate hierarchical Bayesian model.

RESULTS: We globally analyzed 6226 MM cases, 4048 (2897 classified as occupational asbestos exposure at interview) in men and 2178 (780 classified as occupational asbestos exposure at interview) in women. The geographical analysis showed a strong spatial pattern in the distribution of incidence rates in both genders. The multivariate hierarchical Bayesian model decomposed the spatial pattern in occupational and environmental components and consistently identified some known occupational and environmental hot spots. Other areas at high risk for MM occurrence were highlighted, contributing to better characterize environmental exposures from industrial sources and suggesting a role of natural sources in the Alpine region.

CONCLUSION: The spatial pattern highlights areas at higher risk which are characterized by the presence of industrial sources - asbestos-cement, metallurgic, engineering, textile industries - and of natural sources in the Alpine region. The multivariate hierarchical Bayesian model was able to disentangle the geographical distribution of MM cases in two components interpreted as occupational and environmental.}, } @article {pmid32520630, year = {2020}, author = {Tran, T and Egilman, D and Rigler, M}, title = {Response to Roggli et al. (2020) "Talc and mesothelioma: mineral fiber analysis of 65 cases with clinicopathological correlation".}, journal = {Ultrastructural pathology}, volume = {44}, number = {3}, pages = {314-315}, doi = {10.1080/01913123.2020.1778148}, pmid = {32520630}, issn = {1521-0758}, mesh = {Asbestos, Amphibole ; Humans ; *Mesothelioma/pathology ; *Mesothelioma, Malignant ; Mineral Fibers ; Talc ; }, } @article {pmid32517259, year = {2020}, author = {Staumont, B and Jamakhani, M and Costa, C and Vandermeers, F and Sriramareddy, SN and Redouté, G and Mascaux, C and Delvenne, P and Hubert, P and Safari, R and Willems, L}, title = {TGFα Promotes Chemoresistance of Malignant Pleural Mesothelioma.}, journal = {Cancers}, volume = {12}, number = {6}, pages = {}, pmid = {32517259}, issn = {2072-6694}, support = {CDR//Fonds De La Recherche Scientifique - FNRS/ ; Télévie//Fonds De La Recherche Scientifique - FNRS/ ; Asbestos grants//Belgian Foundation against Cancer/ ; }, abstract = {Background: There is no standard chemotherapy for refractory or relapsing malignant pleural mesothelioma (MPM). Our previous reports nevertheless indicated that a combination of an anthracycline (doxorubicin) and a lysine deacetylase inhibitor (valproic acid, VPA) synergize to induce the apoptosis of MPM cells and reduce tumor growth in mouse models. A Phase I/II clinical trial indicated that this regimen is a promising therapeutic option for a proportion of MPM patients. Methods: The transcriptomes of mesothelioma cells were compared after Illumina HiSeq 4000 sequencing. The expression of differentially expressed genes was inhibited by RNA interference. Apoptosis was determined by cell cycle analysis and Annexin V/7-AAD labeling. Protein expression was assessed by immunoblotting. Preclinical efficacy was evaluated in BALB/c and NOD-SCID mice. Results: To understand the mechanisms involved in chemoresistance, the transcriptomes of two MPM cell lines displaying different responses to VPA-doxorubicin were compared. Among the differentially expressed genes, transforming growth factor alpha (TGFα) was associated with resistance to this regimen. The silencing of TGFα by RNA interference correlated with a significant increase in apoptosis, whereas the overexpression of TGFα desensitized MPM cells to the apoptosis induced by VPA and doxorubicin. The multi-targeted inhibition of histone deacetylase (HDAC), HER2 and TGFα receptor (epidermal growth factor receptor/EGFR) improved treatment efficacy in vitro and reduced tumor growth in two MPM mouse models. Finally, TGFα expression but not EGFR correlated with patient survival. Conclusions: Our data show that TGFα but not its receptor EGFR is a key factor in resistance to MPM chemotherapy. This observation may contribute to casting light on the promising but still controversial role of EGFR signaling in MPM therapy.}, } @article {pmid32515059, year = {2020}, author = {Orriols, R and Tarrés, J and Albertí-Casas, C and Rosell-Murphy, M and Abós-Herràndiz, R and Canela-Soler, J}, title = {Malignant asbestos-related disease in a population exposed to asbestos.}, journal = {American journal of industrial medicine}, volume = {63}, number = {9}, pages = {796-802}, doi = {10.1002/ajim.23141}, pmid = {32515059}, issn = {1097-0274}, mesh = {Aged ; Asbestos/*toxicity ; Cities/epidemiology ; Construction Materials/*toxicity ; Environmental Exposure/*adverse effects/analysis ; Female ; Humans ; Incidence ; Lung Neoplasms/*epidemiology/etiology ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Exposure/adverse effects/analysis ; Pleural Neoplasms/*epidemiology/etiology ; Prospective Studies ; Sex Distribution ; Spain/epidemiology ; }, abstract = {OBJECTIVES: The first asbestos fiber cement plant in Spain operated in Cerdanyola, in the Barcelona metropolitan area, between 1907 and 1997. We describe clinical and epidemiological characteristics of patients diagnosed with the malignant asbestos-related disease (ARD) in the area of the plant between 2007 and 2016.

METHODS: A prospective, descriptive study was undertaken in the 12 municipalities of the county of Barcelona most proximate to the plant. We describe malignant ARD cases by time of diagnosis, source of exposure, periods of exposure and latency, and distribution by sex. Cumulative incidence and age-standardized incidence rates (ASIR) are calculated.

RESULTS: Of 477 patients diagnosed with ARD between 2007 and 2016, 128 (26%) presented with asbestos-associated malignancy. Pleural mesothelioma was noted in 105 patients (82.0%) with a linear trend Z-score of -0.2 (NS) in men and 2.7 (P < .01) in women. The highest ASIRs for malignant ARD (6.1/100 000 residents/year; 95% confidence interval [CI], 2.2-13.3) and pleural mesothelioma (4.8/100 000 residents/year; 95% CI, 1.5-11.6) occurred in municipalities closest to the focal point of contamination. The origin of malignant ARD was nonoccupational in 32.2% of men and 81.6% of women (P < .001).

CONCLUSIONS: More than 20 years after the closure of the fiber cement plant, the grave consequences of exposure to asbestos remain. The detection of cases of pleural mesothelioma in men seems to have plateaued whereas in women an ascending trend continues, which principally has its origin in nonoccupational exposures.}, } @article {pmid32509926, year = {2020}, author = {Marques de Sousa, S and Pereira, F and Duarte, M and Marques, M and Vázquez, D and Marques, C}, title = {Malignant Peritoneal Mesothelioma as a Rare Cause of Dyspeptic Complaints and Ascites: A Diagnostic Challenge.}, journal = {GE Portuguese journal of gastroenterology}, volume = {27}, number = {3}, pages = {197-202}, pmid = {32509926}, issn = {2341-4545}, abstract = {INTRODUCTION: Malignant peritoneal mesothelioma (MPM) is a rare malignancy of the mesothelial cells in the peritoneum. The best-defined risk factor is asbestos exposure, but germline mutations in BAP1 also increase susceptibility to this tumor. The diagnosis of MPM is challenging since clinical manifestations are often nonspecific.

CASE PRESENTATION: We describe a case of MPM in a 53-year-old former construction worker with prior asbestos exposure. The clinical presentation was a 3-month history of dyspeptic complaints. As initial workup, abdominal ultrasound and upper gastrointestinal endoscopy were performed. Chronic gastritis due to Helicobacter pylori was detected, which was promptly treated but without symptom relief. Abdominal ultrasound showed small volume ascites with hyperechogenic foci, which was later confirmed on computed tomography scan showing the presence of peritoneal nodules in the greater omentum and mesentery. A thorough investigation was conducted based on the suspicion of peritoneal carcinomatosis. A non-peritoneal primary tumor was not found. Ascitic cytology and immunocytochemical studies were suggestive of mesothelioma. He underwent exploratory laparotomy and inoperable peritoneal disease was observed. Peritoneal biopsy confirmed epithelioid-type MPM. Systemic therapy was initiated with platinum plus pemetrexed with good response. The last follow-up was 38 months after the diagnosis.

DISCUSSION/CONCLUSION: The diagnosis of MPM is challenging since it requires a high degree of suspicion. MPM has a poor prognosis. The standard of treatment recommended is cytoreductive surgery with hyperthermic intraperitoneal chemotherapy. For those who are inoperable, systemic therapy with pemetrexed-cisplatin combination is the alternative. Given the infrequency of disease, it is imperative to ensure patient participation in clinical trials with the purpose of treatment standardization.}, } @article {pmid32492522, year = {2020}, author = {Marsh, GM and Ierardi, AM}, title = {Confidence interval function analysis to evaluate the risk of mesothelioma among an expanded international cohort of cosmetic talc miners and millers.}, journal = {Regulatory toxicology and pharmacology : RTP}, volume = {115}, number = {}, pages = {104696}, doi = {10.1016/j.yrtph.2020.104696}, pmid = {32492522}, issn = {1096-0295}, mesh = {Confidence Intervals ; Cosmetics ; Data Interpretation, Statistical ; Humans ; Mesothelioma/*epidemiology ; Mining ; Occupational Diseases/*epidemiology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*epidemiology ; Risk ; Talc/*adverse effects ; }, abstract = {We used pooled data from international cosmetic talc miner/miller cohorts to determine whether hypothesized increased mesothelioma risks are consistent with the observed data. We evaluated the confidence interval function for the observed pooled mesothelioma SMRs (observed = 1; expected = 3.17, 3.34, or 3.60), and calculated the value of α for the upper 100(1 - 2α)% confidence limit that equals various SMRs of interest (1.5, 2.0, 2.5, 3.0). Using the mid-value estimate of expected number of cases (3.34), the probability (α) that the true mesothelioma SMR is at or above 2.0, or at or above 3.0 is 0.0096 and 0.0005, respectively. Thus, a mesothelioma SMR ≥2.0 is not compatible with the observed pooled data, providing further support for our conclusion that cosmetic talc exposure is not associated with an elevated risk of mesothelioma.}, } @article {pmid32489446, year = {2020}, author = {Alghamdi, ZM and Othman, SA and Al-Yousef, MJ and AlFadel, BZ}, title = {Intrapulmonary location of benign solitary fibrous tumor.}, journal = {Annals of thoracic medicine}, volume = {15}, number = {2}, pages = {98-101}, pmid = {32489446}, issn = {1817-1737}, abstract = {Intrapulmonary solitary fibrous tumors (SFTs) are sporadic mesenchymal neoplasms that typically arise from visceral or parietal pleura. While accounting for <5% of all pleural tumors, SFTs are known to occur in nearly all bodily organs, including nasopharynx, bladder, prostate, soft tissue of neck, buttocks, extremities, and abdominal wall. Such tumors have been previously designated localized fibrous mesothelioma or pleural fibroma. SFTs have no genetic basis and are unrelated to environmental factors such as tobacco smoking or asbestos exposure. Herein, we describe a 24-year-old woman whose clinical presentation mimicked atypical carcinoid tumor. A diagnosis of intrapulmonary SFT was achieved by surgical resection.}, } @article {pmid32475501, year = {2020}, author = {Severson, DT and De Rienzo, A and Bueno, R}, title = {Mesothelioma in the age of "Omics": Before and after The Cancer Genome Atlas.}, journal = {The Journal of thoracic and cardiovascular surgery}, volume = {160}, number = {4}, pages = {1078-1083.e2}, pmid = {32475501}, issn = {1097-685X}, support = {R01 CA120528/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Lung Neoplasms/genetics ; *Mesothelioma/genetics ; }, abstract = {Malignant pleural mesothelioma (MPM) is a highly fatal cancer of the pleura that has been defeating standard and investigational therapies since its first description. The efficacies of chemotherapy, radiotherapy, and surgical therapy are limited, and we have been writing for decades that improved therapies are needed. MPM is born of inflammation, and approximately 80% of cases are associated with the smoldering tissue inflammatory responses against the carcinogenic fibers of asbestos. Emerging data on the use of programmed cell death protein 1 immune checkpoint inhibitors were initially exciting, but response is less than 20% and these agents are finding their place on the list of approaches with narrow efficacy. Molecular targeted therapies have revolutionized the treatment of other cancers, commonly result in striking antitumor responses, and directly embody precision medicine. For an example, we prescribe drugs for some lung adenocarcinomas that target the secondary mutations that develop as a resistance mechanism to their initial targeted therapy. The discovery of molecular therapeutics for any tumor begins with identification of a target through investigation of the genomic, epigenomic, and transcriptomic drivers of its carcinogenesis. Such an advance could revolutionize the treatment of mesothelioma. A comprehensive dissection of MPM’s molecular structure was recently published by 2 groups, the first from the Brigham and Women’s Hospital and then from The Cancer Genome Atlas. In the Invited Expert Opinion article that follows, a practical account of the molecular underpinnings of MPM is eloquently presented by the Brigham group and will inspire the discovery and translation of novel molecular targets by mesothelioma investigators and practitioners.}, } @article {pmid32475021, year = {2020}, author = {Korša, L and Lukač, A and Kovačević, L and Bilić, I and Prutki, M and Marušić, Z}, title = {Breast metastasis as the initial presentation of malignant pleural mesothelioma.}, journal = {The breast journal}, volume = {26}, number = {10}, pages = {2063-2064}, doi = {10.1111/tbj.13898}, pmid = {32475021}, issn = {1524-4741}, mesh = {*Breast Neoplasms ; Female ; Humans ; *Lung Neoplasms/diagnostic imaging ; Male ; *Mesothelioma/diagnostic imaging ; *Mesothelioma, Malignant ; Middle Aged ; *Pleural Neoplasms/diagnostic imaging ; }, abstract = {Metastatic involvement of the breast is far less common than primary breast carcinoma, comprising 0.5%-6.6% of all breast malignancies. Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor with higher incidence among men, particularly smokers, strongly associated with asbestos exposure. The epithelioid type of MPM can represent a diagnostic pitfall in this setting, as it shows similar histologic features to primary breast carcinoma as well as other metastatic epithelioid malignancies. We report a rare case of breast metastasis of malignant pleural mesothelioma in a 61-year-old female.}, } @article {pmid32472158, year = {2020}, author = {Greimelmaier, K and Wohlschläger, J and Probst, A and Hager, T and Wardelmann, E and Werlein, C and Jonigk, D and Müller, KM}, title = {[Mesothelial proliferation of the tunica vaginalis testis].}, journal = {Der Pathologe}, volume = {41}, number = {4}, pages = {406-410}, doi = {10.1007/s00292-020-00797-6}, pmid = {32472158}, issn = {1432-1963}, mesh = {Cell Proliferation ; Diagnosis, Differential ; Humans ; Immunohistochemistry ; *Lung Neoplasms/diagnosis ; Male ; *Mesothelioma/diagnosis ; *Testicular Neoplasms/pathology ; Testis ; Tumor Suppressor Proteins/analysis ; Ubiquitin Thiolesterase/analysis ; }, abstract = {Proliferative changes seen in reactive mesothelial hyperplasia of a hydrocele sac may mimic malignant mesothelioma. There is no immunohistochemical staining that reliably separates benign from malignant mesothelial proliferations. However, the combined analysis of BAP1 by immunohistochemistry and CDKN2A by FISH has been reported to yield both a high specificity and sensitivity in this differential diagnosis. In addition, the evaluation of risk factors such as asbestos exposure or prior traumata may be helpful for the correct diagnosis. Exclusion of stromal invasion, which is diagnostic for malign mesothelioma, is of utmost importance. Therefore, extended histological workup is essential.}, } @article {pmid32435497, year = {2020}, author = {Weber, DG and Casjens, S and Brik, A and Raiko, I and Lehnert, M and Taeger, D and Gleichenhagen, J and Kollmeier, J and Bauer, TT and Brüning, T and Johnen, G and , }, title = {Circulating long non-coding RNA GAS5 (growth arrest-specific transcript 5) as a complement marker for the detection of malignant mesothelioma using liquid biopsies.}, journal = {Biomarker research}, volume = {8}, number = {}, pages = {15}, pmid = {32435497}, issn = {2050-7771}, abstract = {BACKGROUND: For the detection of malignant mesothelioma additional markers are needed besides the established panel consisting of calretinin and mesothelin. The aim of this study was the identification and verification of long non-coding RNAs (lncRNAs) as complementing circulating markers.

METHODS: Candidate lncRNAs were identified in silico using previously published RNA expression profiles and verified using quantitative PCR (qPCR) in mesothelioma cell lines as well as human plasma samples from mesothelioma patients and asbestos-exposed controls.

RESULTS: GAS5 (growth arrest-specific transcript 5) as a single marker is marked by a low sensitivity of 14%, but the combination of GAS5 with calretinin and mesothelin increased the panel's sensitivity from 64 to 73% at a predefined specificity of 97%. Circulating GAS5 is not affected by pleurectomy before blood collection, age, or smoking status.

CONCLUSIONS: GAS5 is verified as an appropriate circulating marker for the supplement of calretinin and mesothelin to detect malignant mesothelioma. Although the sensitivity of GAS5 is too low for the use as a single marker, the addition of GAS5 as a third marker improves the performance of the established marker panel. The benefit of GAS5 for the detection of malignant mesothelioma at early stages needs to be validated in a prospective study.}, } @article {pmid32429446, year = {2020}, author = {Di Gilio, A and Catino, A and Lombardi, A and Palmisani, J and Facchini, L and Mongelli, T and Varesano, N and Bellotti, R and Galetta, D and de Gennaro, G and Tangaro, S}, title = {Breath Analysis for Early Detection of Malignant Pleural Mesothelioma: Volatile Organic Compounds (VOCs) Determination and Possible Biochemical Pathways.}, journal = {Cancers}, volume = {12}, number = {5}, pages = {}, pmid = {32429446}, issn = {2072-6694}, abstract = {Malignant pleural mesothelioma (MPM) is a rare neoplasm, mainly caused by asbestos exposure, with a high mortality rate. The management of patients with MPM is controversial due to a long latency period between exposure and diagnosis and because of non-specific symptoms generally appearing at advanced stage of the disease. Breath analysis, aimed at the identification of diagnostic Volatile Organic Compounds (VOCs) pattern in exhaled breath, is believed to improve early detection of MPM. Therefore, in this study, breath samples from 14 MPM patients and 20 healthy controls (HC) were collected and analyzed by Thermal Desorption-Gas Chromatography-Mass Spectrometry (TD-GC/MS). Nonparametric test allowed to identify the most weighting variables to discriminate between MPM and HC breath samples and multivariate statistics were applied. Considering that MPM is an aggressive neoplasm leading to a late diagnosis and thus the recruitment of patients is very difficult, a promising data mining approach was developed and validated in order to discriminate between MPM patients and healthy controls, even if no large population data are available. Three different machine learning algorithms were applied to perform the classification task with a leave-one-out cross-validation approach, leading to remarkable results (Area Under Curve AUC = 93%). Ten VOCs, such as ketones, alkanes and methylate derivates, as well as hydrocarbons, were able to discriminate between MPM patients and healthy controls and for each compound which resulted diagnostic for MPM, the metabolic pathway was studied in order to identify the link between VOC and the neoplasm. Moreover, five breath samples from asymptomatic asbestos-exposed persons (AEx) were exploratively analyzed, processed and tested by the validated statistical method as blinded samples in order to evaluate the performance for the early recognition of patients affected by MPM among asbestos-exposed persons. Good agreement was found between the information obtained by gold-standard diagnostic methods such as computed tomography CT and model output.}, } @article {pmid32392897, year = {2020}, author = {Abbott, DM and Bortolotto, C and Benvenuti, S and Lancia, A and Filippi, AR and Stella, GM}, title = {Malignant Pleural Mesothelioma: Genetic and Microenviromental Heterogeneity as an Unexpected Reading Frame and Therapeutic Challenge.}, journal = {Cancers}, volume = {12}, number = {5}, pages = {}, pmid = {32392897}, issn = {2072-6694}, abstract = {Mesothelioma is a malignancy of serosal membranes including the peritoneum, pleura, pericardium and the tunica vaginalis of the testes. Malignant mesothelioma (MM) is a rare disease with a global incidence in countries like Italy of about 1.15 per 100,000 inhabitants. Malignant Pleural Mesothelioma (MPM) is the most common form of mesothelioma, accounting for approximately 80% of disease. Although rare in the global population, mesothelioma is linked to industrial pollutants and mineral fiber exposure, with approximately 80% of cases linked to asbestos. Due to the persistent asbestos exposure in many countries, a worldwide progressive increase in MPM incidence is expected for the current and coming years. The tumor grows in a loco-regional pattern, spreading from the parietal to the visceral pleura and invading the surrounding structures that induce the clinical picture of pleural effusion, pain and dyspnea. Distant spreading and metastasis are rarely observed, and most patients die from the burden of the primary tumor. Currently, there are no effective treatments for MPM, and the prognosis is invariably poor. Some studies average the prognosis to be roughly one-year after diagnosis. The uniquely poor mutational landscape which characterizes MPM appears to derive from a selective pressure operated by the environment; thus, inflammation and immune response emerge as key players in driving MPM progression and represent promising therapeutic targets. Here we recapitulate current knowledge on MPM with focus on the emerging network between genetic asset and inflammatory microenvironment which characterize the disease as amenable target for novel therapeutic approaches.}, } @article {pmid32383566, year = {2020}, author = {Kilitci, A and Uygun, N and Emir, ML}, title = {Sarcomatoid Type of Paratesticular Malignant Mesothelioma in a Dry-Cleaning Worker Exposed to Asbestos and Diagnostic Value of WT-1.}, journal = {Puerto Rico health sciences journal}, volume = {39}, number = {1}, pages = {39-44}, pmid = {32383566}, issn = {2373-6011}, mesh = {Asbestos/toxicity ; Humans ; Male ; Mesothelioma, Malignant/*diagnosis/pathology ; Middle Aged ; Occupational Exposure/adverse effects ; Sarcoma/*diagnosis/pathology ; Testicular Neoplasms/*diagnosis/pathology ; WT1 Proteins/analysis ; }, abstract = {Of the 3 major histologic types of malignant paratesticular mesothelioma (MPM) (epithelial, sarcomatoid, and biphasic), many cases of epithelial and biphasic mesothelioma have been reported in the literature. Pure sarcomatoid MPM is the least common but the most aggressive of the 3 major histologic types of mesothelioma cells. It is limited to only 2 cases in the literature The sarcomatoid type of MPM can be confused clinically and histologically with true sarcomas because it is rarely seen. We present a case who had been exposed to asbestos for years due to his involvement in the dry-cleaning industry and who was diagnosed with the sarcomatoid type of MPM but had a relatively prolonged survival not usually seen with this tumor. This report also emphasizes the significance of an immunohistochemical examination, focusing especially on the diagnostic role of WT-1.}, } @article {pmid32382335, year = {2020}, author = {Zhang, G and Yang, DL and Zheng, G and Liang, Y}, title = {Survivin expression as an independent predictor of overall survival in malignant peritoneal mesothelioma.}, journal = {Oncology letters}, volume = {19}, number = {6}, pages = {3871-3880}, pmid = {32382335}, issn = {1792-1074}, abstract = {Malignant peritoneal mesothelioma (MPeM) is an incurable cancer strongly associated with asbestos exposure and characterised by poor prognosis. The aim of the present study was to elucidate the prognostic and predictive value of CD146 and survivin expression in MPeM. Diagnostic biopsies from 60 patients with MPeM were collected and analysed for CD146, survivin and Ki-67 expression using immunohistochemistry. Complete clinical and follow-up information was obtained from patients' records. CD146 was expressed in 31/60 MPeM specimens and survivin in 34/60 specimens, with both expression levels being significantly associated with the Ki-67 labelling index (Ki-67LI). Kaplan-Meier and univariate Cox regression analyses revealed that a lower peritoneal cancer index (PCI), tumour-directed treatment, stage I, lower Ki-67LI and lower CD146 and survivin expression had a statistically positive effect on overall survival (OS). Cox regression analysis revealed that PCI [hazard ratio (HR)=1.99; 95% CI, 1.04-3.83; P=0.038], survivin (HR=1.47; 95% CI, 1.03-2.10; P=0.034) and treatment protocol including intraperitoneal chemotherapy (HR=0.28; 95% CI, 0.14-0.57; P=0.013) and systemic chemotherapy (HR=0.13; 95% CI, 0.04-0.42; P=0.013) retained independent prognostic significance for OS. All of these were included in the nomogram. Calibration curves showed good agreement between nomogram-predicted and observed survival. The C-index of the nomogram for predicting OS was 0.77. A lower PCI, intraperitoneal chemotherapy, systemic chemotherapy and a lower level of survivin were powerful prognostic markers in patients with MPeM. The proposed nomogram provides individual survival prediction for patients with MPeM.}, } @article {pmid32374117, year = {2020}, author = {Barbieri, PG and Calisti, R and Silvestri, S and Calabresi, C and Consonni, D and Angelini, A and Carnevale, F and Cavariani, F and Sala, O}, title = {[About the asbestos and the Position Paper on asbestos of the Italian Society of Occupational Medicine].}, journal = {Epidemiologia e prevenzione}, volume = {44}, number = {1}, pages = {73-83}, doi = {10.19191/EP20.1.P073.019}, pmid = {32374117}, issn = {1120-9763}, mesh = {*Asbestos ; Asbestosis/epidemiology ; Humans ; Italy/epidemiology ; Mesothelioma/epidemiology ; Occupational Diseases/*epidemiology ; Occupational Exposure ; }, abstract = {The SIML Position Paper dedicated to asbestos (PPA) is addressed (mainly) to competent practitioners (CP) for the purposes to provide a guidance about a set of items classified as markedly interesting: the actuality of asbestos exposure and the evaluation of the related risk; the diagnosis of the asbestos related diseases; the shape of the risk functions (namely about mesotheliomas); the causal relationship between exposure and disease; the medical surveillance of the workers currently and previously exposed. The scientific literature doesn't acknowledge the idea that nowadays in Italy the frequency of pleural mesotheliomas deriving from environmental asbestos from outdoor sources exposures is really a relevant item. Inside the SIML PPA the chapter concerning industrial hygiene and environmental monitoring themes shows inaccuracies and deficiencies, so resulting of scarce utility for the CPs that should be called for a more cooperative role in front of the employers. The arguments of the diagnosis of the asbestos related diseases is developed with an undue emphasis upon the differential histological diagnosis of asbestosis and, especially, of pleural mesothelioma: nosographic aspects that hardly are posed to the attention of the CP. A similar emphasis is posed towards the shape of the risk function for pleural mesothelioma, a theme absent from the current practice of the CP such as of other occupational practitioners. In conclusion, next to themes of undoubted interest for the PC, the SIML PPA dwells on the scrutiny of some topics representing critical elements of the current contrast between consultants and valuers in the context of criminal prosecutions: subjects having forensic relevance but far from the "application actuality" for the CP invoked in the PPA. A greater transparency, last but not least, was to have been posed, inside the SIML PPA, in the disclosure of the conflict of interests (COIs) of some Authors, declaring their consultancy in favour of companies.}, } @article {pmid32374111, year = {2020}, author = {Marinaccio, A and Corfiati, M and Binazzi, A and Di Marzio, D and Bonafede, M and Verardo, M and Migliore, E and Gennaro, V and Mensi, C and Schallemberg, G and Mazzoleni, G and Fedeli, U and Negro, C and Romanelli, A and Chellini, E and Grappasonni, I and Pascucci, C and Madeo, G and Romeo, E and Trafficante, L and Carrozza, F and Angelillo, IF and Cavone, D and Cauzillo, G and Tallarigo, F and Tumino, R and Melis, M and , }, title = {The epidemiological surveillance of malignant mesothelioma in Italy (1993-2015): methods, findings, and research perspectives.}, journal = {Epidemiologia e prevenzione}, volume = {44}, number = {1}, pages = {23-30}, doi = {10.19191/EP20.1.P023.014}, pmid = {32374111}, issn = {1120-9763}, mesh = {Adult ; Female ; Humans ; Incidence ; Italy/epidemiology ; Male ; Mesothelioma, Malignant/*epidemiology ; Middle Aged ; Occupational Diseases/epidemiology ; Occupational Exposure/statistics & numerical data ; Population Surveillance ; Registries ; }, abstract = {BACKGROUND: as a legacy of the large asbestos consumption until the definitive ban in 1992, Italy had to tackle a real epidemic of asbestos related diseases. The Italian National Registry of Malignant Mesotheliomas (ReNaM) is a permanent surveillance system of mesothelioma incidence, with a regional structure. Aims, assignments and territorial network of ReNaM are described, as well as data collection, recording and coding procedures.

OBJECTIVES: to describe the Italian epidemiological surveillance system of mesothelioma incidence, to provide updated data about occurrence of malignant mesothelioma in Italy, and to discuss goals, attainments, and expectations of registering occupational cancer.

DESIGN: analysis of data by malignant mesothelioma incident cases surveillance system.

SETTING AND PARTICIPANTS: Italy, network of regional surveillance system, all Italian regions.

MAIN OUTCOME MEASURES: a Regional Operating Centre (COR) is currently established in all the Italian regions, actively searching incident malignant mesothelioma cases from health care institutions. Occupational history, lifestyle habits, and residential history are obtained using a standardized questionnaire, administered to the subject or to the next of kin by a trained interviewer. The extent of dataset, epidemiological parameters, and occupations involved are reported updated at 31.12.2016, and standardized incidence rates are calculated.

RESULTS: at December 2016, ReNaM has collected 27,356 malignant mesothelioma cases, referring to the period of incidence between 1993 and 2015. The modalities of exposure to asbestos have been investigated for 21,387 (78%) and an occupational exposure has been defined for around 70% of defined cases (14,818).

CONCLUSIONS: the Italian experience shows that epidemiological systematic surveillance of asbestos related diseases incidence has a key importance for assessing and monitoring the public health impact of occupational and/or environmental hazards, programming preventive interventions, including remediation plans and information campaigns, and supporting the efficiency of insurance and welfare system. Monitoring the incidence of malignant mesothelioma through a specialized cancer registry is essential to follow-up the health effects of changing modalities and extent of occupational exposures over years and of environmental contamination. Such consolidated surveillance system is recommended also for occupational cancers with low aetiological fraction.}, } @article {pmid32369821, year = {2020}, author = {Campanella, NC and Silva, EC and Dix, G and de Lima Vazquez, F and Escremim de Paula, F and Berardinelli, GN and Balancin, M and Chammas, R and Mendoza Lopez, RV and Silveira, HCS and Capelozzi, VL and Reis, RM}, title = {Mutational Profiling of Driver Tumor Suppressor and Oncogenic Genes in Brazilian Malignant Pleural Mesotheliomas.}, journal = {Pathobiology : journal of immunopathology, molecular and cellular biology}, volume = {87}, number = {3}, pages = {208-216}, doi = {10.1159/000507373}, pmid = {32369821}, issn = {1423-0291}, mesh = {Carcinogenesis ; Cohort Studies ; Female ; *Genes, Tumor Suppressor ; High-Throughput Nucleotide Sequencing ; Humans ; Lung Neoplasms/*genetics ; Male ; Mesothelioma, Malignant/*genetics ; Middle Aged ; *Mutation ; *Oncogenes ; Paraffin Embedding ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a highly lethal disease comprising a heterogeneous group of tumors with challenging to predict biological behavior. The diagnosis is complex, and the histologic classification includes 2 major subtypes of MPM: epithelioid (∼60% of cases) and sarcomatous (∼20%). Its identification depends upon pathological investigation supported by clinical and radiological evidence and more recently ancillary molecular testing. Treatment options are currently limited, with no known targeted therapies available.

OBJECTIVES: To elucidate the mutation profile of driver tumor suppressor and oncogenic genes in a cohort of Brazilian patients.

METHODS: We sequenced 16 driver genes in a series of 43 Brazilian malignant mesothelioma (MM) patients from 3 distinct Brazilian centers. Genomic DNA was extracted from formalin-fixed paraffin-embedded tumor tissue blocks, and the TERT promoter region was amplified by PCR followed by direct capillary sequencing. The Illumina TruSight Tumor 15 was used to evaluate 250 amplicons from 15 genes associated with solid tumors (AKT1, GNA11, NRAS, BRAF, GNAQ, PDGFRA, EGFR, KIT, PIK3CA, ERBB2, KRAS, RET, FOXL2, MET,and TP53). Library preparation with the TruSight Tumor 15 was performed before sequencing at the MiSeq platform. Data analysis was performed using Sophia DDM software.

RESULTS: Out of 43 MPM patients, 38 (88.4%) were epithelioid subtype and 5 (11.6%) were sarcomatoid histotype. Asbestos exposure was present in 15 (39.5%) patients with epithelioid MPM and 3 (60%) patients with sarcomatoid MPM. We found a TERT promoter mutation in 11.6% of MM, and the c.-146C>T mutation was the most common event. The next-generation sequencing was successful in 33 cases. A total of 18 samples showed at least 1 pathogenic, with a median of 1.8 variants, ranging from 1 to 6. The most mutated genes were TP53 and ERBB2 with 7 variants each, followed by NRAS BRAF, PI3KCA, EGFR and PDGFRA with 2 variants each. KIT, AKT1, and FOXL2 genes exhibited 1 variant each. Interestingly, 2 variants observed in the PDGFRA gene are classic imatinib-sensitive therapy.

CONCLUSIONS: We concluded that Brazilian MPM harbor mutation in classic tumor suppressor and oncogenic genes, which might help in the guidance of personalized treatment of MPM.}, } @article {pmid32367143, year = {2020}, author = {Fadel, M and Evanoff, BA and Andersen, JH and d'Errico, A and Dale, AM and Leclerc, A and Descatha, A}, title = {Not just a research method: If used with caution, can job-exposure matrices be a useful tool in the practice of occupational medicine and public health?.}, journal = {Scandinavian journal of work, environment & health}, volume = {46}, number = {5}, pages = {552-553}, pmid = {32367143}, issn = {1795-990X}, mesh = {*Asbestos ; France ; Humans ; Occupational Exposure/*analysis ; *Occupational Medicine ; Occupations ; Public Health ; }, abstract = {The recent editorial by Dr Susan Peters "Although a valuable method in occupational epidemiology, job-exposure matrices are no magic fix" ably describes the strengths and limitations of job-exposure matrix (JEM) approaches in occupational epidemiology research (1). In addition to their use in research, we would like to add that JEM may also be of use in compensation and surveillance efforts in occupational health. JEM could assist the compensation process by supporting the assessment of relevant exposures related to specific health conditions (2). The potential usefulness of a JEM as a decision tool for compensation of work-related musculoskeletal disorders has been examined (3). Because occupational diseases are often under-recognized, another practical application is using a JEM to screen for occupational exposures as part of health surveillance. Use of JEM to screen for asbestos and wood dust exposure in the clinical setting has shown promising results (4-6). By summarizing multiple exposures at a job level (7), JEM may also assist policy-makers in setting priorities for hazards and controls at work, as well as occupational practitioners to target prevention efforts and direct the conduct of more precise exposure measures to particular jobs. Sharing JEM across different countries may be useful in providing estimates of exposures across larger populations to calculate global burden of disease related to occupational exposure. The JEMINI (JEM InterNatIonal) initiative was launched to explore the possibility of developing international JEM that could be used across countries (8). Beginning with physical (biomechanical) exposures, this open group has started homogenizing job coding systems and comparing some available JEM. Estimating differences in the level of exposure between countries will require much more work, without guaranteed success. As Peters mentioned, many limitations exist in the use of JEM. Users of JEM must consider the source of exposure data - expert assessments, data collected from individual workers, or environmental sampling. The coding of occupations is time consuming and can introduce error (9), and more testing of and comparison with automated job coding systems is needed (10). JEM reflect an "average" level of exposure within a job at the expense of individual variation. At population level, JEM can offer a useful estimate of exposures. If used at an individual level in a clinical or compensation setting, JEM cannot replace the professionals involved in exposure assessment but may help them focus their action more effectively on complex situations that require their expertise. In conclusion, these JEM developed for research might also be used as a public health tool, provided that their limitations are properly taken into account. References 1. Peters S. Although a valuable method in occupational epidemiology, job-exposure matrices are no magic fix. Scand J Work Environ Health 2020;46:2314. https://doi.org/10.5271/sjweh.3894 2. Kerbrat J, Descatha A. (The recognition of health consequences of difficult working conditions in France and its evaluation with the use of a job-exposure matrix). Arch Mal Prof Environ. 2018;79:493500. https://doi.org/10.1016/j.admp.2017.12.001 3. Fadel M, Valter R, Quignette A, Descatha A. Usefulness of a job-exposure matrix « MADE » as a decision tool for compensation of work-related musculoskeletal disorders. Eur J Public Health 2019;29:86870. https://doi.org/10.1093/eurpub/cky274 4. Lorentz E, Despreaux T, Quignette A, Chinet T, Descatha A. (Screening of occupational exposure to asbestos and silica by job-exposure matrix among patients with lung cancer and mesothelioma). Rev Mal Respir. 2019;36:108895. https://doi.org/10.1016/j.rmr.2019.08.006 5. Imbernon E, Goldberg M, Spyckerell Y, Steinmetz J, Bonenfant S, Fournier B. (Use of a job-exposure matrix for the screening of occupational exposure to asbestos). Rev Epidemiol Sante Publique 2004;52:717. https://doi.org/10.1016/S0398-7620(04)99018-9 6. Carton M, Bonnaud S, Nachtigal M, Serrano A, Carole C, Bonenfant S, et al. Post-retirement surveillance of workers exposed to asbestos or wood dust: first results of the French national SPIRALE Program. Epidemiol Prev. 2011;35:31523. 7. Guéguen A, Goldberg M, Bonenfant S, Martin JC. Using a representative sample of workers for constructing the SUMEX French general population based job-exposure matrix. Occup Environ Med. 2004;61:58693. https://doi.org/10.1136/oem.2003.010660 8. Descatha A, Evanoff BA, Andersen JH, Fadel M, Ngabirano L, Leclerc A, et al. JEMINI (Job Exposure Matrix InterNatIonal) Initiative: a Utopian Possibility for Helping Occupational Exposure Assessment All Around the World? J Occup Environ Med. 2019;61:e3201. https://doi.org/10.1097/JOM.0000000000001631 9. Petersen SB, Flachs EM, Svendsen SW, Marott JL, Budtz-Jørgensen E, Hansen J, et al. Influence of errors in job codes on job exposure matrix-based exposure assessment in the register-based occupational cohort DOC*X. Scand J Work Environ Health 2020;46:25967. https://doi.org/10.5271/sjweh.3857 10. Buckner-Petty S, Dale AM, Evanoff BA. Efficiency of autocoding programs for converting job descriptors into standard occupational classification (SOC) codes. Am J Ind Med. 2019;62:5968. https://doi.org/10.1002/ajim.22928.}, } @article {pmid32364316, year = {2020}, author = {Trama, A and Proto, C and Signorelli, D and Garassino, MC and Lo Russo, G and Ganzinelli, M and Prelaj, A and Mensi, C and Gangemi, M and Gennaro, V and Chellini, E and Caldarella, A and Angelillo, IF and Ascoli, V and Pascucci, C and Tagliabue, G and Cusimano, R and Bella, F and Falcini, F and Merler, E and Masanotti, G and Ziino, A and Michiara, M and Gola, G and Storchi, C and Mangone, L and Vitale, MF and Cirilli, C and Tumino, R and Scuderi, T and Fanetti, AC and Piffer, S and Tiseo, M and Gatta, G and Botta, L and , }, title = {Treatment patterns among patients with malignant pleural mesothelioma: An Italian, population-based nationwide study.}, journal = {Thoracic cancer}, volume = {11}, number = {6}, pages = {1661-1669}, pmid = {32364316}, issn = {1759-7714}, support = {NA//Associazione Italiana Esposti Amianto (Italian Association of Asbestos Expositions AIEA)/International ; Investigator Grant - IG 2012 number 13534, year 20//Associazione Italiana per la Ricerca sul Cancro (Italian Association for cancer research-AIRC)/International ; RF-INT- 201241451, year 2008//Italian Ministry of Health/International ; }, mesh = {Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Italy/epidemiology ; Male ; Mesothelioma, Malignant/epidemiology/pathology/*therapy ; Middle Aged ; Pleural Neoplasms/epidemiology/pathology/*therapy ; Pneumonectomy/*mortality ; Prognosis ; Radiotherapy/*mortality ; Registries/*statistics & numerical data ; Survival Rate ; Young Adult ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare cancer with a poor prognosis. Centralization of rare cancer in dedicated centers is recommended to ensure expertise, multidisciplinarity and access to innovation. In Italy, expert centers for MPM have not been identified in all regions. We aimed to describe the treatment patterns among MPM patients across different Italian regions and to identify factors associated with the treatment patterns across the regions.

METHODS: We performed an observational study on a random sample of 2026 MPM patients diagnosed in 2003-2008. We included 26 population-based registries covering 70% of the Italian population. To identify factors associated with treatment patterns, across the different regions, we fitted a multinomial logistic regression model adjusted by age, sex, stage, histology and hospital with thoracic surgical department.

RESULTS: MPM patients mostly received chemotherapy alone (41%) or no cancer-directed therapy (36%) especially the older patients. The first course of treatment for MPM patients differed across regions. Patients from Piedmont, Liguria and Campania were more likely to receive no cancer-directed therapy; those living in Tuscany and Sicily were more likely to get surgery; patients from Marche and Lazio were more likely to receive chemotherapy. These differences were not explained by age, sex, stage, histology and availability of a thoracic surgery department.

CONCLUSIONS: There is limited expertise available and lack of a network able to maximize the expertise available may contribute to explaining the results of our study. Our findings support the need to ensure the appropriate care of all MPM patients in reorganizing the health care services.

KEY POINTS: Significant findings of the study: MPM patients mostly received chemotherapy alone or no cancer-directed therapy especially the older patients. The first course of treatment for MPM patients differed across Italian regions.

WHAT THIS STUDY ADDS: Differences in MPM clinical management are not explained by the age, stage, histology nor by the availability of a thoracic surgery department. Limited expertise for MPM contribute to explaining the unequal access to appropriate care for MPM patients in Italy.}, } @article {pmid32354783, year = {2020}, author = {Dyer, C}, title = {Doctor with mesothelioma wins settlement for asbestos exposure in late 1990s.}, journal = {BMJ (Clinical research ed.)}, volume = {369}, number = {}, pages = {m1783}, doi = {10.1136/bmj.m1783}, pmid = {32354783}, issn = {1756-1833}, } @article {pmid34594644, year = {2020}, author = {Chen, M and Wang, H and Zhang, J and Yu, C and Liu, W and Xu, Y}, title = {Distribution of Asbestos Enterprises and Asbestosis Cases - China, 1997-2019.}, journal = {China CDC weekly}, volume = {2}, number = {18}, pages = {305-309}, pmid = {34594644}, issn = {2096-7071}, abstract = {Asbestos is classified as a Class I Carcinogen by the International Agency for Research on Cancer (IARC) because exposure causes mesothelioma and lung cancer in addition to asbestosis and plaques. So far, asbestos has been banned in 67 countries, but chrysotile, a commonly encountered form of asbestos, is still widely used in China and most developing countries. Most asbestos-caused cancers are not reported, recorded, and compensated in many countries.

WHAT IS ADDED BY THIS REPORT?: Enterprises manufacturing asbestos products have been migrating from economically developed Eastern China to relatively underdeveloped central and western regions between 2010 and 2019. Asbestosis cases reported in Tianjin, Beijing, Shandong, Xinjiang, Gansu, Qinghai, and Sichuan accounted for a large proportion of the total cases in China, which was inconsistent with the distribution of asbestos-related enterprises (AREs). The reported asbestosis cases versus total pneumoconiosis cases declined from 2.81% to 0.39% from 2006-2017, and this proportion reached 0.69% in 2018.

Robust occupational and environmental health assessments and reporting are needed to define the epidemiology of asbestos-related lung diseases, and management of using asbestos and existing products containing asbestos need strengthening and follow-up. Enterprises should be encouraged to use safer substitutes and gradually ban asbestos materials in China.}, } @article {pmid32352426, year = {2020}, author = {Angelini, A and Chellini, E and Parducci, D and Puccetti, M and Mauro, L}, title = {[Not Available].}, journal = {La Medicina del lavoro}, volume = {111}, number = {2}, pages = {126-132}, pmid = {32352426}, issn = {0025-7818}, mesh = {*Asbestos/toxicity ; Humans ; *Lung Neoplasms/epidemiology ; *Mesothelioma/epidemiology ; Occupational Diseases ; *Occupational Exposure ; *Pleural Neoplasms/epidemiology ; }, abstract = {UNLABELLED: «Reconstruction of the asbestos exposure in a textile company producing sewing threads through the use of an unusual information source».

BACKGROUND:: The Tuscan Regional Operating Center (ROC) of Malignant Mesotheliomas has identified a cluster of 11 cases of malignant mesothelioma occurred in a textile plant manufacturing sewing thread. Using the common research method, the ROC had not previously been able to identify the specific sources of asbestos exposure causing such a large cluster.

OBJECTIVES:: The ROC’s objective was to review all cases of the cluster and to better identify their occupational asbestos exposures.

METHODS:: The cases’ occupational histories of asbestos exposure have been reviewed, using information deriving from the annual reports sent to the Tuscany Region since 1988 by all the asbestos removal companies according to the Law no. 257/1992, article 9, and from interviews to former employees of the plant.

RESULTS:: The work cycle has been reconstructed and enriched with the new information about the asbestos presence and its uses in the plant. The eleven cases were all reclassified as “certainly occupational exposed” given that the new collected information depicted a widespread asbestos pollution of the workplace during the period of employment of all cases.

CONCLUSIONS:: Using different sources of information, in addition to those traditionally collected through questionnaires, to reconstruct past asbestos exposuresallowed us to clarify the existence of the cluster of mesothelioma cases and the highest level of occupational asbestos exposure was attributed to all cases with consequent activation of the medico-legal procedure.}, } @article {pmid32345664, year = {2020}, author = {Lacerenza, S and Ciregia, F and Giusti, L and Bonotti, A and Greco, V and Giannaccini, G and D'Antongiovanni, V and Fallahi, P and Pieroni, L and Cristaudo, A and Lucacchini, A and Mazzoni, MR and Foddis, R}, title = {Putative Biomarkers for Malignant Pleural Mesothelioma Suggested by Proteomic Analysis of Cell Secretome.}, journal = {Cancer genomics & proteomics}, volume = {17}, number = {3}, pages = {225-236}, pmid = {32345664}, issn = {1790-6245}, mesh = {Aged ; Biomarkers, Tumor/*blood ; Case-Control Studies ; Cell Line, Tumor ; Female ; GPI-Linked Proteins/blood ; Humans ; Lung Neoplasms/*blood/pathology ; Male ; Mesothelin ; Mesothelioma/*blood/pathology ; Mesothelioma, Malignant ; Middle Aged ; Oxidoreductases Acting on Sulfur Group Donors/blood ; Pleural Neoplasms/*blood/pathology ; Proteome/*metabolism ; ROC Curve ; Saposins/blood ; Secretory Pathway ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) a rare neoplasm linked to asbestos exposure is characterized by a poor prognosis. Soluble mesothelin is currently considered the most specific diagnostic biomarker. The aim of the study was to identify novel biomarkers by proteomic analysis of two MPM cell lines secretome.

MATERIALS AND METHODS: The protein patterns of MPM cells secretome were examined and compared to a non-malignant mesothelial cell line using two-dimensional gel electrophoresis coupled to mass spectrometry. Serum levels of candidate biomarkers were determined in MPM patients and control subjects.

RESULTS: Two up-regulated proteins involved in cancer biology, prosaposin and quiescin Q6 sulfhydryl oxidase 1, were considered candidate biomarkers. Serum levels of both proteins were significantly higher in MPM patients than control subjects. Combining the data of each receiver-operating characteristic analysis predicted a good diagnostic accuracy.

CONCLUSION: A panel of the putative biomarkers represents a promising tool for MPM diagnosis.}, } @article {pmid32330840, year = {2020}, author = {Ahmadzada, T and Kao, S and Reid, G and Clarke, S and Grau, GE and Hosseini-Beheshti, E}, title = {Extracellular vesicles as biomarkers in malignant pleural mesothelioma: A review.}, journal = {Critical reviews in oncology/hematology}, volume = {150}, number = {}, pages = {102949}, doi = {10.1016/j.critrevonc.2020.102949}, pmid = {32330840}, issn = {1879-0461}, mesh = {Biomarkers ; *Cell-Derived Microparticles ; *Exosomes ; *Extracellular Vesicles ; Humans ; *Mesothelioma ; }, abstract = {Extracellular vesicles (EV) are secreted by all cells, including cancer cells, as a mode of intercellular transport and communication. The main types of EV known to date include exosomes, microvesicles and apoptotic bodies, as well as oncosomes and large oncosomes, which are specific to cancer cells. These different EV populations carry specific cargo from one cell to another to stimulate a specific response. They can be found in all body fluids and can be detected in liquid biopsies. EV released from mesothelioma cells can reveal important information about the molecules and signalling pathways involved in the development and progression of the tumour. The presence of tumour-derived EV in circulating body fluids makes them potential novel biomarkers for early diagnosis, prognostication and surveillance of cancer. In this review, we explore the characteristics and functional roles of EV reported in the literature, with a focus on their role in malignant pleural mesothelioma.}, } @article {pmid32330788, year = {2020}, author = {Filetti, V and Falzone, L and Rapisarda, V and Caltabiano, R and Eleonora Graziano, AC and Ledda, C and Loreto, C}, title = {Modulation of microRNA expression levels after naturally occurring asbestiform fibers exposure as a diagnostic biomarker of mesothelial neoplastic transformation.}, journal = {Ecotoxicology and environmental safety}, volume = {198}, number = {}, pages = {110640}, doi = {10.1016/j.ecoenv.2020.110640}, pmid = {32330788}, issn = {1090-2414}, mesh = {Adult ; Asbestos/*toxicity ; Asbestos, Amphibole/*toxicity ; Biomarkers/analysis ; Cell Line ; Cell Transformation, Neoplastic/*chemically induced ; *Environmental Exposure ; Epithelium/*drug effects ; Female ; Gene Expression Profiling ; Humans ; Male ; MicroRNAs/*genetics ; Middle Aged ; Neoplasms, Mesothelial/*chemically induced/diagnosis ; Sicily ; }, abstract = {Fluoro-edenite (FE) is a silicate mineral identified in the lava products of Monte Calvario from stone quarries located in the southeast of Biancavilla, a small city of the Etnean volcanic complex (Sicily, Italy). Inhalation of FE fibers has been associated with a higher incidence of Malignant Mesothelioma (MM), a highly aggressive neoplasm of the serosal membranes lining the pleural cavity. Only 5% of MM patients are diagnosed at an early stage and the median survival is approximate 6-12 months. Many diagnostic biomarkers have been proposed for MM. Several studies demonstrated that microRNAs (miRNAs) may be used as good non-invasive diagnostics, as well as prognostic biomarkers for various human diseases, including cancer. On these bases, the aim of the present study was to identify a set of miRNAs involved in the development and progression of MM and potentially used as diagnostic biomarkers. For these purposes, in silico analyses were performed on healthy/exposed to asbestos fibers subjects vs. patients with MM. These analyses revealed a set of miRNAs strictly involved in MM by merging the lists of miRNAs found differentially expressed in the three miRNA expression datasets analyzed. The result of these computational evaluations allowed the execution of functional in vitro experiments performed on normal pleural mesothelial cell line (MeT-5A) and MM cell line (JU77) in order to test the carcinogenetic effects and epigenetic modulation induced by FE exposure. The in vitro results showed that the expression levels of hsa-miR-323a-3p vary significantly in both supernatant- and cell-derived miRNAs derived from treated and untreated cells. Secreted and cellular hsa-miR-101-3p in MeT-5A treated with FE fibers and JU77 cells showed different trends of expression. As regard hsa-miR-20b-5p, there was no differential expression between secreted and cellular hsa-miR-20b-5p. This miRNA has been shown a significant up-regulation in JU77 cells vs. control and treated MeT-5A. As a future plan, translational analyses will be performed on a subset of patients chronically exposed to FE fibers to further verify the clinical role of such miRNAs in high-risk individuals and their possible use as biomarkers of FE exposure or MM early onset.}, } @article {pmid32328661, year = {2020}, author = {Girardi, P and Merler, E and Ferrante, D and Silvestri, S and Chellini, E and Angelini, A and Luberto, F and Fedeli, U and Oddone, E and Vicentini, M and Barone-Adesi, F and Cena, T and Mirabelli, D and Mangone, L and Roncaglia, F and Sala, O and Menegozzo, S and Pirastu, R and Azzolina, D and Tunesi, S and Miligi, L and Perticaroli, P and Pettinari, A and Cuccaro, F and Nannavecchia, AM and Bisceglia, L and Marinaccio, A and Pavone, VLM and Magnani, C}, title = {Factors Affecting Asbestosis Mortality Among Asbestos-Cement Workers in Italy.}, journal = {Annals of work exposures and health}, volume = {64}, number = {6}, pages = {622-635}, doi = {10.1093/annweh/wxaa037}, pmid = {32328661}, issn = {2398-7316}, mesh = {*Asbestos/adverse effects ; Asbestos, Serpentine ; *Asbestosis ; Female ; Humans ; Italy/epidemiology ; Male ; Middle Aged ; *Occupational Exposure/adverse effects ; }, abstract = {OBJECTIVES: This study was performed with the aim of investigating the temporal patterns and determinants associated with mortality from asbestosis among 21 cohorts of Asbestos-Cement (AC) workers who were heavily exposed to asbestos fibres.

METHODS: Mortality for asbestosis was analysed for a cohort of 13 076 Italian AC workers (18.1% women). Individual cumulative asbestos exposure index was calculated by factory and period of work weighting by the different composition of asbestos used (crocidolite, amosite, and chrysotile). Two different approaches to analysis, based on Standardized Mortality Ratios (SMRs) and Age-Period-Cohort (APC) models were applied.

RESULTS: Among the considered AC facilities, asbestos exposure was extremely high until the end of the 1970s and, due to the long latency, a peak of asbestosis mortality was observed after the 1990s. Mortality for asbestosis reached extremely high SMR values [SMR: males 508, 95% confidence interval (CI): 446-563; females 1027, 95% CI: 771-1336]. SMR increased steeply with the increasing values of cumulative asbestos exposure and with Time Since the First Exposure. APC analysis reported a clear age effect with a mortality peak at 75-80 years; the mortality for asbestosis increased in the last three quintiles of the cumulative exposure; calendar period did not have a significant temporal component while the cohort effect disappeared if we included in the model the cumulative exposure to asbestos.

CONCLUSIONS: Among heaviest exposed workers, mortality risk for asbestosis began to increase before 50 years of age. Mortality for asbestosis was mainly determined by cumulative exposure to asbestos.}, } @article {pmid32326213, year = {2020}, author = {Cellai, F and Bonassi, S and Cristaudo, A and Bonotti, A and Neri, M and Ceppi, M and Bruzzone, M and Milić, M and Munnia, A and Peluso, M}, title = {Chromatographic Detection of 8-Hydroxy-2'-Deoxyguanosine in Leukocytes of Asbestos Exposed Workers for Assessing Past and Recent Carcinogen Exposures.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {10}, number = {4}, pages = {}, pmid = {32326213}, issn = {2075-4418}, support = {NA//Istituto Nazionale per l'Assicurazione Contro Gli Infortuni sul Lavoro/ ; NA//Regione Toscana/ ; }, abstract = {Asbestos fibers include a group of silicate minerals that occur in the environment and are widely employed in occupational settings. Asbestos exposure has been associated to various chronic diseases; such as pulmonary fibrosis; mesothelioma; and lung cancer; often characterized by a long period of latency. Underlying mechanisms that are behind the carcinogenic effect of asbestos have not been fully clarified. Therefore; we have conducted an epidemiological study to evaluate the relationship between 8-hydroxy-2'-deoxyguanosine (8-oxodG), one of the most reliable biomarkers of oxidative stress and oxidative DNA damage; and asbestos exposure in the peripheral blood of residents in Tuscany and Liguria regions; Italy; stratified by occupational exposure to this carcinogen. Levels of 8-oxodG were expressed such as relative adduct labeling (RAL); the frequency of 8-oxodG per 10[5] deoxyguanosine was significantly higher among exposed workers with respect to the controls; i.e., 3.0 ± 0.2 Standard Error (SE) in asbestos workers versus a value of 1.3 ± 0.1 (SE) in unexposed controls (p < 0.001). When the relationship with occupational history was investigated; significant higher levels of 8-oxodG were measured in current and former asbestos workers vs. healthy controls; 3.1 ± 0.3 (SE) and 2.9 ± 0.2 (SE), respectively. After stratification for occupational history; a significant 194% excess of adducts was found in workers with 10 or more years of past asbestos exposure (p < 0.001). 8-oxodG can be used for medical surveillance programs of cohorts of workers with past and recent exposures to carcinogens for the identification of subjects requiring a more intense clinical surveillance.}, } @article {pmid32318342, year = {2020}, author = {Ferrari, L and Carugno, M and Mensi, C and Pesatori, AC}, title = {Circulating Epigenetic Biomarkers in Malignant Pleural Mesothelioma: State of the Art and critical Evaluation.}, journal = {Frontiers in oncology}, volume = {10}, number = {}, pages = {445}, pmid = {32318342}, issn = {2234-943X}, abstract = {Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer, which originates from the mesothelial cells of the pleura and is associated with asbestos exposure. In light of its aggressive nature, late diagnosis and dismal prognosis, there is an urgent need for identification of biomarkers in easily accessible samples (such as blood) for early diagnosis of MPM. In the last 10 years, epigenetic markers, such as DNA methylation and microRNAs (miRNAs), have gained popularity as possible early diagnostic and prognostic biomarkers in cancer research. The aim of this review is to provide a critical analysis of the current evidences on circulating epigenetic biomarkers for MPM and on their translational potential to the clinical practice for early diagnosis and for prognosis.}, } @article {pmid32312030, year = {2020}, author = {Loreto, C and Caltabiano, R and Graziano, ACE and Castorina, S and Lombardo, C and Filetti, V and Vitale, E and Rapisarda, G and Cardile, V and Ledda, C and Rapisarda, V}, title = {Defense and protection mechanisms in lung exposed to asbestiform fiber: the role of macrophage migration inhibitory factor and heme oxygenase-1.}, journal = {European journal of histochemistry : EJH}, volume = {64}, number = {2}, pages = {}, pmid = {32312030}, issn = {2038-8306}, mesh = {Animals ; Asbestos, Amphibole/*toxicity ; Asbestosis/*physiopathology ; Female ; Fibroblasts/drug effects ; Heme Oxygenase-1/*metabolism ; Humans ; Immunohistochemistry ; Inflammation/physiopathology ; Lung/*drug effects/pathology ; Macrophage Migration-Inhibitory Factors/*metabolism ; Male ; Sheep ; }, abstract = {Fluoro-edenite (FE), an asbestiform fiber, is responsible for many respiratory pathologies: chronic obstructive diseases, pleural plaques, fibrosis, and malignant mesothelioma. Macrophage migration inhibitory factor (MIF) is one of the first cytokines produced in response to lung tissue damage. Heme oxygenase-1 (HO-1) is a protein with protective effects against oxidative stress. It is up regulated by several stimuli including pro-inflammatory cytokines and factors that promote oxidative stress. In this research, the in vivo model of sheep lungs naturally exposed to FE was studied in order to shed light on the pathophysiological events sustaining exposure to fibers, by determining immunohistochemical lung expression of MIF and HO-1. Protein levels expression of HO-1 and MIF were also evaluated in human primary lung fibroblasts after exposure to FE fibers in vitro. In exposed sheep lungs, MIF and HO-1 immunoexpression were spread involving the intraparenchymal stroma around bronchioles, interstitium between alveoli, alveolar epithelium and macrophages. High MIF immunoexpression prevails in macrophages. Similar results were obtained in vitro, but significantly higher values were only detected for HO-1 at concentrations of 50 and 100 μg/mL of FE fibers. MIF and HO-1 expressions seem to play a role in lung self-protection against uncontrolled chronic inflammation, thus counteracting the strong link with cancer development, induced by exposure to FE. Further studies will be conducted in order to add more information about the role of MIF and HO-1 in the toxicity FE-induced.}, } @article {pmid32308151, year = {2020}, author = {Sturchio, E and Berardinelli, MG and Boccia, P and Zanellato, M and Gioiosa, S}, title = {MicroRNAs diagnostic and prognostic value as predictive markers for malignant mesothelioma.}, journal = {Archives of environmental & occupational health}, volume = {75}, number = {8}, pages = {471-482}, doi = {10.1080/19338244.2020.1747966}, pmid = {32308151}, issn = {2154-4700}, mesh = {Animals ; Asbestos/toxicity ; Biomarkers, Tumor/analysis ; Humans ; Lung Neoplasms/*genetics ; Mesothelioma/*genetics ; Mesothelioma, Malignant ; MicroRNAs/*analysis ; Occupational Exposure/adverse effects ; Predictive Value of Tests ; Prognosis ; }, abstract = {Malignant mesothelioma is an aggressive tumor resistant to current therapies with a latency period ranging between 20 and 60 years, caused by inhalation of asbestos fibers, that continues to represent a social and healthcare issue. The high percentage of people exposed to asbestos for professional or environmental reasons is associated with the high biopersistence of its fibers and with its widespread use in the last century. Approximately 20-40% of men report an occupational history that might have caused the workplace exposure (criteria Helsinki, 1997). Some authors are evaluating the possible use of bioindicators as a screening and early diagnosis tool. In this regard, the use of microRNAs has been proposed as powerful diagnostic and prognostic biomarkers for many tumors and human diseases. This review focuses on the current state of knowledge on the key role of microRNAs expression as new malignant mesothelioma biomarkers, in early clinical diagnostic applications.}, } @article {pmid32301278, year = {2020}, author = {Barbarino, M and Cesari, D and Bottaro, M and Luzzi, L and Namagerdi, A and Bertolino, FM and Bellan, C and Proietti, F and Somma, P and Micheli, M and de Santi, MM and Guazzo, R and Mutti, L and Pirtoli, L and Paladini, P and Indovina, P and Giordano, A}, title = {PRMT5 silencing selectively affects MTAP-deleted mesothelioma: In vitro evidence of a novel promising approach.}, journal = {Journal of cellular and molecular medicine}, volume = {24}, number = {10}, pages = {5565-5577}, pmid = {32301278}, issn = {1582-4934}, mesh = {Cell Line, Tumor ; Chromatography, Liquid ; Epithelial-Mesenchymal Transition/genetics ; *Gene Deletion ; *Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; *Gene Silencing ; Humans ; Immunohistochemistry ; Mesothelioma/*genetics/metabolism/pathology ; Protein-Arginine N-Methyltransferases/*genetics ; Purine-Nucleoside Phosphorylase/*genetics ; Tandem Mass Spectrometry ; }, abstract = {Malignant mesothelioma (MM) is an aggressive asbestos-related cancer of the serous membranes. Despite intensive treatment regimens, MM is still a fatal disease, mainly due to the intrinsic resistance to current therapies and the lack of predictive markers and new valuable molecular targets. Protein arginine methyltransferase 5 (PRMT5) inhibition has recently emerged as a potential therapy against methylthioadenosine phosphorylase (MTAP)-deficient cancers, in which the accumulation of the substrate 5'-methylthioadenosine (MTA) inhibits PRMT5 activity, thus sensitizing the cells to further PRMT5 inhibition. Considering that the MTAP gene is frequently codeleted with the adjacent cyclin-dependent kinase inhibitor 2A (CDKN2A) locus in MM, we assessed whether PRMT5 could represent a therapeutic target also for this cancer type. We evaluated PRMT5 expression, the MTAP status and MTA content in normal mesothelial and MM cell lines. We found that both administration of exogenous MTA and stable PRMT5 knock-down, by short hairpin RNAs (shRNAs), selectively reduced the growth of MTAP-deleted MM cells. We also observed that PRMT5 knock-down in MTAP-deficient MM cells reduced the expression of E2F1 target genes involved in cell cycle progression and of factors implicated in epithelial-to-mesenchymal transition. Therefore, PRMT5 targeting could represent a promising new therapeutic strategy against MTAP-deleted MMs.}, } @article {pmid32290761, year = {2020}, author = {Laubenthal, TG}, title = {Regulated Asbestos Analysis: EPA Polarized Light Microscopy Method and the Implications for Reported Fiber Sizes.}, journal = {New solutions : a journal of environmental and occupational health policy : NS}, volume = {30}, number = {2}, pages = {83-85}, doi = {10.1177/1048291120917952}, pmid = {32290761}, issn = {1541-3772}, mesh = {*Asbestos ; Asbestos, Serpentine ; Humans ; *Mesothelioma ; Microscopy, Polarization ; }, } @article {pmid32290540, year = {2020}, author = {Vimercati, L and Cavone, D and Delfino, MC and Caputi, A and De Maria, L and Sponselli, S and Corrado, V and Ferri, GM and Serio, G}, title = {Asbestos Air Pollution: Description of a Mesothelioma Cluster Due to Residential Exposure from an Asbestos Cement Factory.}, journal = {International journal of environmental research and public health}, volume = {17}, number = {8}, pages = {}, pmid = {32290540}, issn = {1660-4601}, mesh = {Aged ; *Air Pollution ; *Asbestos/toxicity ; Environmental Exposure/adverse effects ; Female ; Humans ; Italy/epidemiology ; *Lung Neoplasms/chemically induced/epidemiology ; Male ; *Mesothelioma/chemically induced/epidemiology ; Middle Aged ; *Occupational Exposure/adverse effects ; }, abstract = {The study describes a cluster of 71 malignant mesothelioma cases among Bari residents without asbestos exposure other than residential exposure. This small cohort, as expected, was composed of a majority of females (56.34%) with a M/F ratio of 0.8, ages ≤ 65 years old (52.11%) and the epithelioid morphological type (78.87%). Sixty-four subjects (90.14%) lived between 10 m and 1000 m from the asbestos cement factory (Fibronit), and the latency length was longer than 55 years for 25 subjects (35.21%). The adjusted risk (adjusted OR) of observing the epithelial form of mesothelioma among subjects living at small distances from Fibronit was high (OR = 1.870 (0.353-9.905)) for people living 550-1000 m from the site and for those living less than 550 m from the site (OR = 1.470 (0.262-8.248)). Additionally, the subjects with a high length of exposure showed a relevant risk of epithelioid mesothelioma both for 21-40 years of exposure (OR = 2.027 (0.521-7.890)) and more than 40 years of exposure (OR = 2.879 (0.651-12.736)). All of the estimates were high but not significant because this transitional study has a typically low power. The adjustment for latency showed the same trend. Using detailed information collected by the regional mesothelioma registry, this study provided evidence of a continuing health impact of the Fibronit asbestos cement factory in Bari on the resident population.}, } @article {pmid32282287, year = {2020}, author = {Metintas, S and Ak, G and Metintas, M}, title = {Potential years of life and productivity loss due to malignant mesothelioma in Turkey.}, journal = {Archives of environmental & occupational health}, volume = {75}, number = {8}, pages = {464-470}, doi = {10.1080/19338244.2020.1747380}, pmid = {32282287}, issn = {2154-4700}, mesh = {Adult ; *Efficiency ; Female ; Humans ; *Life Expectancy ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; Mesothelioma, Malignant ; Middle Aged ; Mortality/*trends ; Population Surveillance ; Risk Assessment ; Risk Factors ; Turkey/epidemiology ; }, abstract = {The study aimed to calculate years of life lost (YLL) and years of potential life lost (YPLL) due to malignant mesothelioma (MM) in Turkey. YLL was computed by estimating the difference between age at death due to MM and the expected death age. To calculate YPLL, all deaths above 65 years (retirement age) were disregarded. Of the 5,617 deaths due to MM in the study period, 3,241 (57.70%) were male and 2,376 (42.30%) were female. The median YLL and YPLL were 16.58 and 25.13 for males and 19.83 and 28.50 years for females. YLL and YPLL were shorter in males than females (p < 0.001). Premature mortality cost per death was $ 45,963.57 (2.23 times higher for males). MM is associated with high YLL, YPLL and economic burden in a country with environmental asbestos exposure in the rural areas.}, } @article {pmid32253443, year = {2020}, author = {Marinaccio, A and Consonni, D and Mensi, C and Mirabelli, D and Migliore, E and Magnani, C and Di Marzio, D and Gennaro, V and Mazzoleni, G and Girardi, P and Negro, C and Romanelli, A and Chellini, E and Grappasonni, I and Madeo, G and Romeo, E and Ascoli, V and Carrozza, F and Angelillo, IF and Cavone, D and Tumino, R and Melis, M and Curti, S and Brandi, G and Mattioli, S and Iavicoli, S and , }, title = {Association between asbestos exposure and pericardial and tunica vaginalis testis malignant mesothelioma: a case-control study and epidemiological remarks.}, journal = {Scandinavian journal of work, environment & health}, volume = {46}, number = {6}, pages = {609-617}, pmid = {32253443}, issn = {1795-990X}, mesh = {Adolescent ; Adult ; Aged ; *Asbestos ; Case-Control Studies ; Child ; Child, Preschool ; Female ; Humans ; Incidence ; Infant ; Infant, Newborn ; Italy/epidemiology ; Male ; Mesothelioma, Malignant/*epidemiology ; Middle Aged ; Occupational Diseases/*epidemiology ; *Occupational Exposure ; Pericardium/*pathology ; Registries ; Testicular Neoplasms/*epidemiology ; Young Adult ; }, abstract = {Objectives The purposes of this study are to describe the epidemiology of pericardial and tunica vaginalis testis mesothelioma and assess the role of asbestos exposure for these rare diseases. Methods Based on incident pericardial and tunica vaginalis testis mesothelioma cases collected from the Italian national mesothelioma registry (ReNaM) in the period 1993-2015, incidence rates, survival median period and prognostic factors have been evaluated. A case-control study has been performed to analyze the association with asbestos exposure (occupational and non-occupational) for these diseases. Results Between 1993 and 2015, 58 pericardial (20 women and 38 men) and 80 tunica vaginalis testis mesothelioma cases have been registered with a mean annual standardized (world standard population as reference) incidence rates of 0.049 (per million) in men and 0.023 in women for the pericardial site, and 0.095 for tunica vaginalis testis mesothelioma. Occupational exposure to asbestos was significantly associated with the risk of the diseases [odds ratio (OR) 3.68, 95% confidence interval (CI) 1.85-7.31 and OR 3.42, 95% CI 1.93-6.04 in pericardial and tunica vaginalis testis mesothelioma, respectively]. The median survival was 2.5 months for pericardial and 33.0 months for tunica vaginalis testis mesotheliomas. Age was the main predictive factor for survival for both anatomical sites. Conclusions For the first time in an analytical study, asbestos exposure was associated with pericardial and tunica vaginalis testis mesothelioma risk, supporting the causal role of asbestos for all anatomical sites. The extreme rarity of the diseases, the poor survival and the prognostic role of age have been confirmed based on population and nationwide mesothelioma registry data.}, } @article {pmid32249197, year = {2020}, author = {Lau, B and Boyer, M and Lee, JH and Kao, S}, title = {Clinical Trials Eligibility of Patients With Malignant Pleural Mesothelioma: Use of Novel Therapies and Outcomes.}, journal = {Clinical lung cancer}, volume = {21}, number = {4}, pages = {378-383.e1}, doi = {10.1016/j.cllc.2020.01.007}, pmid = {32249197}, issn = {1938-0690}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal, Humanized/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Bevacizumab/administration & dosage ; Cisplatin/administration & dosage ; Clinical Trials, Phase I as Topic ; Clinical Trials, Phase III as Topic ; *Eligibility Determination ; Female ; Follow-Up Studies ; Humans ; Male ; Mesothelioma, Malignant/*drug therapy/pathology ; Middle Aged ; *Patient Selection ; Pleural Neoplasms/*drug therapy/pathology ; Prognosis ; Randomized Controlled Trials as Topic ; Retrospective Studies ; Survival Rate ; }, abstract = {INTRODUCTION: Studies of bevacizumab and pembrolizumab in the treatment of malignant pleural mesothelioma suggest anticancer efficacy; clinical trial populations are not reflective of real-world patients. We aimed to determine the proportion of real-world patients who would be eligible for trials, identify patients who participated in clinical trials, and examine treatment and outcome data.

PATIENTS AND METHODS: Consecutive patients with unresectable malignant pleural mesothelioma seen at our center from January 2012 to July 2018 were assessed with regards to their eligibility for Mesothelioma Avastin Cisplatin Study (MAPS) and KEYNOTE-028 clinical trials. Prognostic information, treatment use, and overall survival (OS) data were also collected.

RESULTS: A total of 133 patients were included: 50% and 37%, respectively, did not meet trial eligibility for MAPS or KEYNOTE-028, most commonly owing to age ≥75 (23%), Eastern Cooperative Oncology Group performance status of ≥2 (21%), concomitant medication (21%), or comorbidity (12%). MAPS eligibility did not correlate with use of bevacizumab (P = .30) or improved OS (P = .87). Eligibility for KEYNOTE-028 correlated with pembrolizumab use (P < .001), but not improved OS (P = .21). Patients who received an investigational anticancer therapy on any clinical trial had improved OS: 32.4 (95% CI, 23.9-40.9) months versus 20.5 (95% CI, 15.8-25.3) months (P = .01).

CONCLUSION: Only ≤63% of our patients were eligible for these trials, highlighting the differences between real-world patients and the highly select trial population. Our patients who participated in clinical trials had superior OS, further emphasizing the selection bias in the trial population.}, } @article {pmid32248600, year = {2020}, author = {Okazaki, Y and Chew, SH and Nagai, H and Yamashita, Y and Ohara, H and Jiang, L and Akatsuka, S and Takahashi, T and Toyokuni, S}, title = {Overexpression of miR-199/214 is a distinctive feature of iron-induced and asbestos-induced sarcomatoid mesothelioma in rats.}, journal = {Cancer science}, volume = {111}, number = {6}, pages = {2016-2027}, pmid = {32248600}, issn = {1349-7006}, support = {//Ministry of Education, Culture, Sports, Science and Technology/ ; Young Scientist (B)(23790440)//Japan Society for the Promotion of Science/ ; Young Scientist (B)(25860292)//Japan Society for the Promotion of Science/ ; JP17H04064//JSPS Kakenhi/ ; JP19H05462//JSPS Kakenhi/ ; JPMJCR19H4//JST CREST/ ; }, mesh = {Animals ; Asbestos/toxicity ; Cell Line ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Iron/toxicity ; Lung Neoplasms/genetics/metabolism/*pathology ; Mesothelioma/genetics/metabolism/*pathology ; Mesothelioma, Malignant ; MicroRNAs/*biosynthesis ; Peritoneal Neoplasms/genetics/metabolism/*pathology ; Rats ; Twist-Related Protein 1/*biosynthesis ; }, abstract = {Malignant mesothelioma (MM) is one of the most lethal tumors in humans. The onset of MM is linked to exposure to asbestos, which generates reactive oxygen species (ROS). ROS are believed to be derived from the frustrated phagocytosis and the iron in asbestos. To explore the pathogenesis of MM, peritoneal MM was induced in rats by the repeated intraperitoneal injection of iron saccharate and nitrilotriacetate. In the present study, we used microarray techniques to screen the microRNA (miR) expression profiles of these MM. We observed that the histological subtype impacted the hierarchical clustering of miR expression profiles and determined that miR-199/214 is a distinctive feature of iron saccharate-induced sarcomatoid mesothelioma (SM). Twist1, a transcriptional regulator of the epithelial-mesenchymal transition, has been shown to activate miR-199/214 transcription; thus, the expression level of Twist1 was examined in iron-induced and asbestos-induced mesotheliomas in rats. Twist1 was exclusively expressed in iron saccharate-induced SM but not in the epithelioid subtype. The Twist1-miR-199/214 axis is activated in iron saccharate-induced and asbestos-induced SM. The expression levels of miR-214 and Twist1 were correlated in an asbestos-induced MM cell line, suggesting that the Twist1-miR-199/214 axis is preserved. MeT5A, an immortalized human mesothelial cell line, was used for the functional analysis of miR. The overexpression of miR-199/214 promoted cellular proliferation, mobility and phosphorylation of Akt and ERK in MeT5A cells. These results indicate that miR-199/214 may affect the aggressive biological behavior of SM.}, } @article {pmid32242530, year = {2020}, author = {Ramos-Bonilla, JP and Marsili, D and Comba, P}, title = {Epidemiological research as a driver of prevention: the Sibaté study. Commentary.}, journal = {Annali dell'Istituto superiore di sanita}, volume = {56}, number = {1}, pages = {6-9}, doi = {10.4415/ANN_20_01_03}, pmid = {32242530}, issn = {2384-8553}, mesh = {Academies and Institutes ; Asbestos/analysis/*toxicity ; Colombia/epidemiology ; Conservation of Natural Resources/*legislation & jurisprudence ; Construction Materials ; Environmental Exposure ; *Epidemiologic Studies ; Female ; Humans ; Intersectoral Collaboration ; Male ; *Manufacturing and Industrial Facilities ; Mesothelioma/epidemiology/etiology/*prevention & control ; Occupational Exposure ; Pleural Neoplasms/epidemiology/etiology/*prevention & control ; Soil Pollutants/analysis ; Universities ; Urban Health ; Waste Disposal Facilities ; }, abstract = {Although asbestos exposure and risks can be prevented, only five countries in Latin America have banned asbestos, including Colombia. Beginning in 2011, a collaboration between the Istituto Superiore di Sanità in Italy and Universidad de los Andes in Colombia was established, bringing together relevant expertise aiming to improve our understanding of the asbestos problem. An important result of this collaboration was a recently published study conducted in Sibaté, Colombia, a municipality where an asbestos-cement facility has operated since 1942. The evidence collected suggests the presence of a mesothelioma cluster in Sibaté. Landfilled zones with an underground layer of friable asbestos were also discovered in the urban area of the municipality. The importance of this type of collaboration can go beyond understanding the impact of asbestos at the local level, which is crucial, and may also contribute in solving unanswered questions of the problem in countries that banned asbestos decades ago.}, } @article {pmid32223452, year = {2020}, author = {van Zandwijk, N and Reid, G and Frank, AL}, title = {Asbestos-related cancers: the 'Hidden Killer' remains a global threat.}, journal = {Expert review of anticancer therapy}, volume = {20}, number = {4}, pages = {271-278}, doi = {10.1080/14737140.2020.1745067}, pmid = {32223452}, issn = {1744-8328}, mesh = {Animals ; Asbestos/*toxicity ; Asbestos, Amphibole/toxicity ; Asbestos, Serpentine/toxicity ; Humans ; Lung Neoplasms/epidemiology/etiology ; Mesothelioma/epidemiology/etiology ; Occupational Diseases/epidemiology/*etiology ; Occupational Exposure/*adverse effects ; }, abstract = {Introduction: Asbestos, the most frequent cause of occupational cancer, continues to be consumed on a massive scale, with millions of people exposed on a daily basis. This review explains why we have failed in curtailing the silent epidemic of asbestos-related disease and why the numbers of asbestos victims are likely to remain high. Emerging and developed countries have to be reminded that asbestos exposure has yet to become a problem of the past. The worldwide spread of asbestos, followed by the surge of asbestos-related cancers, resembles the lung cancer epidemic caused by smoking and stimulated by manufacturers.Areas covered: Underreporting of malignant mesothelioma and asbestos-induced lung cancer, frequently-used arguments in the amphibole/chrysotile debate and the conclusion from bona-fide research organizations, that all forms of asbestos are carcinogenic, are reviewed. Special attention is paid to the consequences of ubiquitous environmental asbestos and the 'changing face' of malignant mesothelioma in countries with heavy asbestos use in the past.Expert opinion: Experts in oncology, respiratory medicine, occupational and public health, and basic researchers must take responsibility and acknowledge the ongoing silent epidemic of asbestos-related diseases. The call for a world-wide asbestos ban is more urgent than ever.}, } @article {pmid32213537, year = {2020}, author = {Hoon, SN and Fyfe, K and Peddle-McIntyre, CJ and Bowyer, S and Hawkins, F and Jeffery, E and Chih, HJ and Creaney, J and Nowak, A and Brims, F}, title = {Randomised placebo-controlled cross-over study examining the role of anamorelin in mesothelioma (The ANTHEM study): rationale and protocol.}, journal = {BMJ open respiratory research}, volume = {7}, number = {1}, pages = {}, pmid = {32213537}, issn = {2052-4439}, mesh = {Absorptiometry, Photon ; Appetite Stimulants/adverse effects/*therapeutic use ; Australia ; Body Composition/drug effects ; Cachexia/*complications/*drug therapy/etiology/physiopathology ; Clinical Trials, Phase II as Topic ; Cross-Over Studies ; Double-Blind Method ; Humans ; Hydrazines/adverse effects/*therapeutic use ; Linear Models ; Mesothelioma, Malignant/*complications ; Muscle Strength/drug effects ; Oligopeptides/adverse effects/*therapeutic use ; Pilot Projects ; Quality of Life ; Randomized Controlled Trials as Topic ; Weight Gain/drug effects ; }, abstract = {INTRODUCTION: Cachexia is common in malignant mesothelioma (MM); half of patients have malnutrition and low skeletal muscle mass. Malnourished patients have worse quality of life (QoL). Weight loss is strongly associated with poor survival. Anamorelin is an oral ghrelin receptor agonist that improves appetite, body weight and QoL in advanced cancer. The aim of this study is to examine the efficacy of anamorelin in improving appendicular skeletal muscle mass (ASM) and patient-reported outcomes in patients with MM with cachexia.

METHODS AND ANALYSIS: A single-centre, phase II, randomised, placebo-controlled cross-over pilot study with 28-day treatment periods and 3-day washout. Forty patients will be randomised. Primary outcome is change in ASM relative to height measured by dual energy X-ray absorptiometry at end of period 1. Secondary outcomes include cancer-specific and cachexia-related QoL, objective physical activity, dietary intake and adverse events. Eligible patients will have confirmed MM, Eastern Cooperative Oncology Group 0-2, expected survival >3 months and cachexia (defined as >5% weight loss in 6 months or body mass index <20 kg/m[2] with weight loss >2%).

ETHICS AND DISSEMINATION: Ethical approval has been granted. Results will be reported in peer-reviewed publications.

TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (U1111-1240-6828).}, } @article {pmid32208261, year = {2020}, author = {Neitzel, RL and Sayler, SK and Demond, AH and d'Arcy, H and Garabrant, DH and Franzblau, A}, title = {Measurement of asbestos emissions associated with demolition of abandoned residential dwellings.}, journal = {The Science of the total environment}, volume = {722}, number = {}, pages = {137891}, pmid = {32208261}, issn = {1879-1026}, support = {P30 ES017885/ES/NIEHS NIH HHS/United States ; }, abstract = {Many cities are revitalizing their urban cores through the demolition of abandoned residential dwellings (ARDs). However, data regarding the emissions of asbestos during such an operation are sparse. We measured airborne asbestos emissions from emergency demolitions (demolitions on structures deemed too dangerous to enter and remove asbestos) of ARDs in Detroit. High-flow air sampling was conducted during ARD demolitions. Air samples were analyzed using Phased Contrast Microscopy (PCM), and a subset using Transmission Electron Microscopy (TEM). One hundred and one air samples were collected on 25 emergency demolitions. Fifty-four of the 101 PCM samples (53%) exceeded the limit of detection (LOD). However, only 2 of 46 TEM samples (4%) exceeded the LOD for asbestos; these latter samples were from two different demolitions and each contained a single chrysotile asbestos fiber. Using conservative exposure assumptions and commonly-accepted risk estimation formulae, we estimated the lifetime risk of mesothelioma and lung cancer combined to be less than one case per one million people. Emissions of airborne asbestos during emergency (unabated) ARD demolition operations appear to be negligible. As a result, the associated health risk for asbestos-related disease is also negligible. Reconsideration of current regulatory mandates for asbestos abatement in ARDs may be warranted.}, } @article {pmid32206576, year = {2020}, author = {Gray, SG and Mutti, L}, title = {Immunotherapy for mesothelioma: a critical review of current clinical trials and future perspectives.}, journal = {Translational lung cancer research}, volume = {9}, number = {Suppl 1}, pages = {S100-S119}, pmid = {32206576}, issn = {2218-6751}, abstract = {At the clinical level the role of immunotherapy in cancer is currently at a pivotal point. Therapies such as checkpoint inhibitors are being approved at many levels in cancers such as non-small cell lung cancer (NSCLC). Mesothelioma is a rare orphan disease associated with prior exposure to asbestos, with a dismal prognosis. Various clinical trials for checkpoint inhibitors have been conducted in this rare disease, and suggest that such therapies may play a role as a treatment option for a proportion of patients with this cancer. Most recently approved as a salvage therapy in mesothelioma was granted in Japan, regulatory approval for their use in the clinic elsewhere lags. In this article we review the current pertinent clinical trials of immunotherapies in malignant mesothelioma, discuss the current issues that may affect the clinical outcomes of such therapies and further evaluate potential candidate new avenues that may become future targets for immunotherapy in this cancer.}, } @article {pmid32206572, year = {2020}, author = {Yoshikawa, Y and Emi, M and Nakano, T and Gaudino, G}, title = {Mesothelioma developing in carriers of inherited genetic mutations.}, journal = {Translational lung cancer research}, volume = {9}, number = {Suppl 1}, pages = {S67-S76}, pmid = {32206572}, issn = {2218-6751}, abstract = {Malignant mesothelioma is associated with the exposure to asbestos fibers. Recent discovery of the BAP1 cancer syndrome, a Mendelian disorder with high-penetrance autosomal dominant inheritance fostered the genotyping for nucleotide-level or larger structural alteration of germline DNA. Inherited heterozygous mutations of the BAP1 gene increase the susceptibility to carcinogenic fibers, leading to a concept of gene x environment interaction (GxE) as a pathogenetic mechanism of mesothelioma. Several studies on cohorts of unselected patients with mesothelioma or on familial/early-onset cohorts of mesothelioma cases converged on BAP1 as the more frequent germline mutated gene, followed by other genes involved in DNA repair and homologous recombination. Evidence has been emerging that patients with mesothelioma carrying germline mutations of BAP1 and of other genes, such as those involved in DNA repair and tumor suppressor genes, have better prognosis and higher chemosensitivity when compared with patients with germline wildtype Bap1. We report here a germline genomic analysis targeted 22 genes in a cohort of 101 Japanese patients irrespective of asbestos exposure, age at diagnosis, or personal or family history of cancer. By comparing the results with the Human Genetic Variation Database (HGVD) and the Genome Aggregation Database (gnomAD) we selected rare germline variants with a Combined Annotation Dependent Depletion (CADD) >20. We show here that 31 of 101 subjects were carrying 25 rare variants in 14 genes, neither reported in the HGVD nor in the gnomAD database for 14/25 variants. Besides pathogenic variants of BAP1, rare missense variants were found in genes encoding lysine-specific histone methyltransferase SETD2 and SETDB1 and genes encoding subunits of the mSWI/SNF chromatin remodeling complex. The complete scenario of the genetic background consisting of pathogenic germline variants required for the predisposition and GxE for pathogenesis of mesothelioma appears complex, and further large-scale studies are warranted.}, } @article {pmid32206570, year = {2020}, author = {Carbone, M and Gazdar, A and Butel, JS}, title = {SV40 and human mesothelioma.}, journal = {Translational lung cancer research}, volume = {9}, number = {Suppl 1}, pages = {S47-S59}, pmid = {32206570}, issn = {2218-6751}, abstract = {Simian virus 40 (SV40) is a DNA tumor virus capable of infecting and transforming human mesothelial (HM) cells in vitro. Hamsters injected intracardially to expose most tissue types to SV40 preferentially develop mesotheliomas. In humans, asbestos is the main cause of mesothelioma, and asbestos and SV40 are co-carcinogens in transforming HM cells in tissue culture and in causing mesothelioma in hamsters. Laser microdissection experiments conducted in the laboratory of Adi Gazdar demonstrated that SV40 was present specifically in the malignant mesothelioma cells and not in nearby stromal cells. Further experiments demonstrated that SV40 remains episomal in HM cells and astrocytes because of the production of a long antisense RNA that represses viral capsid protein production. Thus, the potent SV40 oncoprotein, T-antigen (Tag), is expressed, but because the capsid proteins are not produced, the cells are not lysed and, instead, become transformed. Together this evidence suggests that SV40 may contribute to the development of mesotheliomas in humans. However, epidemiological evidence to support this hypothesis is lacking. This chapter also summarizes the introduction of SV40, a monkey virus, into the human population as an unrecognized contaminant of early poliovaccines. In addition to mesotheliomas, SV40 now is linked with brain cancers, osteosarcomas, and lymphomas in humans. Explanations are provided for the apparent geographic variations in SV40 prevalence and for controversies about the role of SV40 in human cancer.}, } @article {pmid32206569, year = {2020}, author = {Gaudino, G and Xue, J and Yang, H}, title = {How asbestos and other fibers cause mesothelioma.}, journal = {Translational lung cancer research}, volume = {9}, number = {Suppl 1}, pages = {S39-S46}, pmid = {32206569}, issn = {2218-6751}, abstract = {Mesothelioma has long been associated with the exposure to asbestos, which was largely used in manufacturing activities. Toxicology studies in vitro and in vivo demonstrated that asbestos fibers were carcinogenic, and epidemiology studies revealed that asbestos exposure was paralleled by the increase in the incidence of mesothelioma and related mortality rates. More recently, the role of chronic inflammation and the molecular mechanisms involved in carcinogenesis by mineral fibers were elucidated following the discovery of the roles of HMGB1 and inflammasome. A change of paradigm was the discovery of a prevalence of mesotheliomas attributable to inherited mutations of cancer susceptibility genes. The discovery of BAP1 as a predisposition gene for the development of familial mesothelioma and other cancers implemented genome studies in patients with mesothelioma and routine clinical surveys in individuals at risk to identify germline mutations associated with cancers included in the BAP1 syndrome. A further progress in the approach to asbestos-related malignancy was the adoption of combined genetics and environmental analyses according to the model of gene-environment (GxE) interactions. This review aims at updating on the most recently discovered mechanisms of tumorigenesis and the pivotal role of GxE interactions.}, } @article {pmid32206568, year = {2020}, author = {Alpert, N and van Gerwen, M and Taioli, E}, title = {Epidemiology of mesothelioma in the 21[st] century in Europe and the United States, 40 years after restricted/banned asbestos use.}, journal = {Translational lung cancer research}, volume = {9}, number = {Suppl 1}, pages = {S28-S38}, pmid = {32206568}, issn = {2218-6751}, abstract = {Research has established a strong association between asbestos exposure and malignant mesothelioma, a deadly form of cancer. Since the early 1980's many countries have restricted or banned the production of asbestos, leading to a decline of occupational asbestos exposure in many industrialized countries. However, some countries continue to use asbestos, and worldwide rates of mesothelioma are still increasing. Because of the long latency between exposure and mesothelioma occurrence and the persistence of environmental exposure, incidence rates (IR) may decrease very slowly for several years ahead. In this review, we examine estimates of asbestos consumption before widespread asbestos regulations and the trends in incidence and mortality rates, as well as changes over time for the United States and Europe. In some countries with earlier asbestos restrictions, mesothelioma incidence has been in a modest decline over time. However, asbestos exposure is still a burden worldwide and legislative action is needed to obtain a full ban. The pattern of mesothelioma is shifting from a mostly male disease to a disease that affects females as well in substantial numbers. Studies on unknown sources of asbestos exposure, of other sources of natural exposure to asbestos and asbestos-like fibers, as well as of individual genetic susceptibility to asbestos fibers are needed.}, } @article {pmid32206566, year = {2020}, author = {Carbone, M}, title = {This special volume of mesothelioma is dedicated to my friend Adi Gazdar.}, journal = {Translational lung cancer research}, volume = {9}, number = {Suppl 1}, pages = {S1-S2}, doi = {10.21037/tlcr.2020.01.15}, pmid = {32206566}, issn = {2218-6751}, support = {R01 CA198138/CA/NCI NIH HHS/United States ; R01 CA237235/CA/NCI NIH HHS/United States ; R01 ES030948/ES/NIEHS NIH HHS/United States ; }, } @article {pmid32187018, year = {2020}, author = {Goricar, K and Kovac, V and Dodic-Fikfak, M and Dolzan, V and Franko, A}, title = {Evaluation of soluble mesothelin-related peptides and MSLN genetic variability in asbestos-related diseases.}, journal = {Radiology and oncology}, volume = {54}, number = {1}, pages = {86-95}, pmid = {32187018}, issn = {1581-3207}, mesh = {Aged ; Alleles ; Asbestos ; Asbestosis/*blood ; Carcinogens ; Enzyme-Linked Immunosorbent Assay/methods ; Female ; GPI-Linked Proteins/*blood/chemistry/*genetics ; Genetic Variation ; Genotype ; Humans ; Male ; Mesothelin ; Mesothelioma, Malignant/*blood/etiology/mortality ; Middle Aged ; Peptides/blood/genetics ; Peritoneal Neoplasms/blood/etiology/mortality ; Polymorphism, Genetic ; Protein Isoforms/blood/genetics ; Protein Kinases ; Statistics, Nonparametric ; }, abstract = {Background Asbestos exposure is associated with increased risk of several diseases, including malignant mesothelioma (MM). Cell surface glycoprotein mesothelin is overexpressed in MM and serum soluble mesothelin-related peptides (SMRP) were already proposed as a diagnostic or prognostic biomarker in MM. However, interindividual variability in serum SMRP levels limits the clinical usefulness. Our primary objective was to investigate the influence of MSLN rs1057147 on serum SMRP levels in asbestos-exposed subjects and patients with asbestos-related diseases as well as on survival in MM. Subjects and methods Among 782 asbestos-exposed subjects and patients with asbestos-related diseases, 154 had MM. Serum SMRP levels were determined using sandwich enzyme-linked immunosorbent assay. All subjects were genotyped for MSLN rs1057147 polymorphism using competitive allele-specific polymerase chain reaction. Nonparametric tests, logistic and Cox regression were used in statistical analysis to compare different subject groups. Results MM patients had significantly higher SMRP levels than all other subjects (p < 0.001). Compared to wild-type MSLN rs1057147 genotype, both heterozygotes and carriers of two polymorphic alleles had significantly higher SMRP levels among subjects without MM (p < 0.001), but not in MM patients (p = 0.424). If genotype information was included, specificity of SMRP increased from 88.5% to 92.7% for the optimal cutoff value. Overall survival was significantly shorter in MM patients carrying at least one polymorphic rs1057147 allele (HR = 1.72, 95% CI = 1.15-2.55, p = 0.008). Conclusions MSLN genetic variability affects serum SMRP levels and was associated with shorter survival of MM patients. Combination of genetic and serum factors could therefore serve as a better diagnostic or prognostic biomarker in MM patients.}, } @article {pmid32183600, year = {2020}, author = {Funahashi, S and Okazaki, Y and Akatsuka, S and Takahashi, T and Sakumi, K and Nakabeppu, Y and Toyokuni, S}, title = {Mth1 deficiency provides longer survival upon intraperitoneal crocidolite injection in female mice.}, journal = {Free radical research}, volume = {54}, number = {2-3}, pages = {195-205}, doi = {10.1080/10715762.2020.1743285}, pmid = {32183600}, issn = {1029-2470}, mesh = {Animals ; Asbestos, Crocidolite/*adverse effects/*metabolism ; DNA Repair Enzymes/*deficiency ; Female ; Injections, Intraperitoneal/*methods ; Mice ; Phosphoric Monoester Hydrolases/*deficiency ; }, abstract = {Exposure to asbestos fiber is central to mesothelial carcinogenesis. Recent sequencing studies on human and rodent malignant mesothelioma (MM) revealed frequently mutated genes, including CDKN2A, BAP1 and NF2. Crocidolite directly or indirectly catalyses the generation of hydroxyl radicals, which appears to be the major driving force for mesothelial mutations. DNA base modification is an oxidative DNA damage mechanism, where 8-hydroxy-2'-deoxyguanosine (8-OHdG) is the most abundant modification both physiologically and pathologically. Multiple distinct mechanisms work together to decrease the genomic level of 8-OHdG through the enzymatic activities of Mutyh, Ogg1 and Mth1. Knockout of one or multiple enzymes is not lethal but increases the incidence of tumors. Here, we used single knockout (KO) mice to test whether the deficiency of these three genes affects the incidence and prognosis of asbestos-induced MM. Intraperitoneal injection of 3 mg crocidolite induced MM at a fraction of 14.8% (4/27) in Mth1 KO, 41.4% (12/29) in Mutyh KO and 24.0% (6/25) in Ogg1 KO mice, whereas 31.7% (20/63) induction was observed in C57BL/6 wild-type (Wt) mice. The lifespan of female Mth1 KO mice was longer than that of female Wt mice (p = 0.0468). Whole genome scanning of MM with array-based comparative genomic hybridization revealed rare genomic alterations compared to MM in rats and humans. These results indicate that neither Mutyh deficiency nor Ogg1 deficiency promotes crocidolite-induced MM in mice, but the sanitizing nucleotide pool with Mth1 is advantageous in crocidolite-induced mesothelial carcinogenesis.}, } @article {pmid32183579, year = {2020}, author = {Roggli, VL and Carney, JM and Sporn, TA and Pavlisko, EN}, title = {Talc and mesothelioma: mineral fiber analysis of 65 cases with clinicopathological correlation.}, journal = {Ultrastructural pathology}, volume = {44}, number = {2}, pages = {211-218}, doi = {10.1080/01913123.2020.1737286}, pmid = {32183579}, issn = {1521-0758}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/adverse effects/analysis ; Female ; Humans ; Male ; Mesothelioma, Malignant/*chemistry ; Middle Aged ; Mineral Fibers/adverse effects/*analysis ; Peritoneal Neoplasms/*chemistry ; Pleural Neoplasms/*chemistry ; Talc/adverse effects/*analysis ; }, abstract = {Malignant mesothelioma is strongly associated with prior asbestos exposure. Recently there has been interest in the role of talc exposure in the pathogenesis of mesothelioma. We have analyzed lung tissue samples from a large series of malignant mesothelioma patients. Asbestos bodies were counted by light microscopy and mineral fiber concentrations for fibers 5 µm or greater in length were determined by scanning electron microscopy equipped with an energy dispersive spectrometer. The values were compared with 20 previously published controls. Among 609 patients with mesothelioma, talc fibers were detected in 375 (62%) and exceeded our control values in 65 (11%). Elevated talc levels were found in 48/524 men (9.2%) and 17/85 women (20%). Parietal pleural plaques were identified in 30/51 informative cases (59%) and asbestosis in 5/62 informative cases (8%). Commercial amphiboles (amosite and/or crocidolite) were elevated in 52/65 (80%) and noncommercial amphiboles (tremolite, actinolite or anthophyllite) in 41/65 (63%). Both were elevated in 34/65 (52%). Asbestos body counts by light microscopy were elevated in 53/64 informative cases (83%). A history of working in industries associated with asbestos exposure and increased mesothelioma risk was identified in 36/48 cases in men, and a history of exposure as household contacts of an occupationally exposed individual was identified in 12/17 cases in women. We conclude that among patients with mesothelioma, the vast majority have talc levels indistinguishable from background. Of the remaining 11% with elevated talc levels, the vast majority (80%) have elevated levels of commercial amphibole fibers.}, } @article {pmid32175619, year = {2020}, author = {Emory, TS and Maddox, JC and Kradin, RL}, title = {Malignant mesothelioma following repeated exposures to cosmetic talc: A case series of 75 patients.}, journal = {American journal of industrial medicine}, volume = {63}, number = {6}, pages = {484-489}, pmid = {32175619}, issn = {1097-0274}, mesh = {Adult ; Air Pollutants, Occupational/*adverse effects/analysis ; Asbestos, Amphibole/adverse effects/analysis ; Barbering ; Beauty Culture ; Female ; Humans ; Lung Neoplasms/epidemiology/etiology ; Male ; Mesothelioma, Malignant/*epidemiology/etiology ; Middle Aged ; Occupational Diseases/*epidemiology/etiology ; Occupational Exposure/*adverse effects/analysis ; Pleural Neoplasms/epidemiology/etiology ; Talc/*adverse effects/analysis ; Time Factors ; }, abstract = {BACKGROUND: Asbestos is the primary known cause of malignant mesothelioma. Some cosmetic talc products have been shown to contain asbestos. Recently, repeated exposures to cosmetic talc have been implicated as a cause of mesothelioma.

METHODS: Seventy-five individuals (64 females; 11 males) with malignant mesothelioma, whose only known exposure to asbestos was repeated exposures to cosmetic talcum powders, were reviewed in medical-legal consultation. Out of the 75 cases, 11 were examined for asbestiform fibers.

RESULTS: All subjects had pathologically confirmed malignant mesothelioma. The mean age at diagnosis was 61 ± 17 years. The mean latency from exposure to diagnosis was 50 ± 13 years. The mean exposure duration was 33 ± 16 years. Four mesotheliomas (5%) occurred in individuals working as barbers/cosmetologists, or in a family member who swept the barber shop. Twelve (16%) occurred in individuals less than 45 years old (10 females; 2 males). Forty-eight mesotheliomas were pleural (40 females; 8 males), 23 were peritoneal (21 females; 2 males). Two presented with concomitant pleural and peritoneal disease. There was one pericardial, and one testicular mesothelioma. The majority (51) were of the epithelioid histological subtype, followed by 13 biphasic, 8 sarcomatoid, 2 lymphohistiocytoid, and 1 poorly differentiated. Of the 11 individuals whose nontumorous tissues were analyzed for the presence of asbestiform fibers, all showed the presence of anthophyllite and/or tremolite asbestos.

CONCLUSIONS: Mesotheliomas can develop following exposures to cosmetic talcum powders. These appear to be attributable to the presence of anthophyllite and tremolite contaminants in cosmetic talcum powder.}, } @article {pmid32169964, year = {2020}, author = {Napolitano, A and Antoine, DJ and Pellegrini, L and Baumann, F and Pagano, I and Pastorino, S and Goparaju, CM and Prokrym, K and Canino, C and Pass, HI and Carbone, M and Yang, H}, title = {Expression of Concern: HMGB1 and Its Hyperacetylated Isoform are Sensitive and Specific Serum Biomarkers to Detect Asbestos Exposure and to Identify Mesothelioma Patients.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {26}, number = {6}, pages = {1529}, doi = {10.1158/1078-0432.CCR-20-0338}, pmid = {32169964}, issn = {1557-3265}, } @article {pmid32156681, year = {2020}, author = {Viscardi, G and Di Liello, R and Morgillo, F}, title = {How I treat malignant pleural mesothelioma.}, journal = {ESMO open}, volume = {4}, number = {Suppl 2}, pages = {e000669}, pmid = {32156681}, issn = {2059-7029}, mesh = {Humans ; Lung Neoplasms/*pathology/*therapy ; Mesothelioma/*pathology/*therapy ; Mesothelioma, Malignant ; Pleural Neoplasms/*therapy ; }, abstract = {Malignant pleural mesothelioma is a rare and aggressive malignancy mostly associated with occupational asbestos exposure. Prognosis is poor and only highly selected patients may benefit from aggressive surgical management, also as part of a multimodal approach. In advanced disease, the combination of pemetrexed and platinum remains the only established treatment, while efficacy evidence of second line chemotherapy is lacking. Thus, a deeper knowledge of biology of the disease and more effective treatments are urgently needed. Refer to specialised centres with multidisciplinary expertise is mandatory, as well as inclusion of patients in clinical trials is advisable whenever possible. In all stages of disease focus on symptoms control is paramount.}, } @article {pmid32142836, year = {2020}, author = {Paajanen, J and Laaksonen, S and Kettunen, E and Ilonen, I and Vehmas, T and Salo, J and Räsänen, J and Sutinen, E and Ollila, H and Mäyränpää, MI and Myllärniemi, M and Wolff, H}, title = {Histopathological features of epithelioid malignant pleural mesotheliomas in patients with extended survival.}, journal = {Human pathology}, volume = {98}, number = {}, pages = {110-119}, doi = {10.1016/j.humpath.2020.02.007}, pmid = {32142836}, issn = {1532-8392}, mesh = {Epithelioid Cells/*pathology ; Female ; Humans ; Lung Neoplasms/mortality/*pathology/surgery ; Male ; Mesothelioma/mortality/*pathology/surgery ; Mesothelioma, Malignant ; Necrosis ; Neoplasm Grading ; Pleural Neoplasms/mortality/*pathology/surgery ; Time Factors ; Treatment Outcome ; }, abstract = {Diffuse malignant mesothelioma (DMM) of the pleura is a rare and aggressive disease, wherein the long-term survival (LTS) rate is low. The epithelioid subtype is the most prevalent form of DMM with the best prognosis. To study prognostic histopathologic factors associated with extended survival in epithelioid DMM, we examined 43 tumors from patients with survival more than five years (LTSs) and compared the findings with 84 tumors from a reference group (RG) with average survival. We analyzed the tumors considering previously published histopathological prognostic features and attempted to identify additional morphological features predictive of extended survival. Most of the LTS tumors presented with nuclear grade I (n = 34, 90%) and a tubulopapillary growth pattern (n = 30, 70%). One LTS tumor had necrosis. In contrast, nuclear grade II (n = 49, 61%) and solid growth pattern (n = 59, 70%) were more frequent in the RG, and necrosis was present in 16 (19%) tumors. We also evaluated the association of asbestos lung tissue fiber burden quantified from autopsy samples with histopathological features and found that elevated asbestos fiber was associated with higher nuclear grade (P < 0.001) and the presence of necrosis (P = 0.021). In univariate survival analysis, we identified the following three novel morphological features associated with survival: exophytic polypoid growth pattern, tumor density, and single mesothelium layered tubular structures. After adjustments, low nuclear grade (P < 0.001) and presence of exophytic polypoid growth (P = 0.024) were associated with prolonged survival. These results may aid in estimating DMM prognosis.}, } @article {pmid32133285, year = {2020}, author = {Nowak, AK and Brosseau, S and Cook, A and Zalcman, G}, title = {Antiangiogeneic Strategies in Mesothelioma.}, journal = {Frontiers in oncology}, volume = {10}, number = {}, pages = {126}, pmid = {32133285}, issn = {2234-943X}, abstract = {There is a strong rationale for inhibiting angiogenesis in mesothelioma. Vascular endothelial growth factor (VEGF) is an autocrine growth factor in mesothelioma and a potent mitogen for mesothelial cells. Further, the abnormal tumor vasculature promotes raised interstitial pressure and hypoxia, which may be detrimental to both penetration and efficacy of anticancer agents. Antiangiogenic agents have been trialed in mesothelioma for close to two decades, with early phase clinical trials testing vascular targeting agents, the VEGF-A targeting monoclonal antibody bevacizumab, and numerous tyrosine kinase inhibitors, many with multiple targets. None of these have shown efficacy which has warranted further development as single agents in any line of therapy. Whilst a randomized phase II trial combining the multitargeted tyrosine kinase inhibitor nintedanib with platinum/pemetrexed chemotherapy was positive, these results were not confirmed in a subsequent phase III study. The combination of cisplatin and pemetrexed with bevacizumab, in appropriately selected patients, remains the only anti-angiogenic combination showing efficacy in mesothelioma. Extensive efforts to identify biomarkers of response have not yet been successful.}, } @article {pmid32123850, year = {2019}, author = {Fan, X and McLaughlin, C and Robinson, C and Ravasini, J and Schelch, K and Johnson, T and van Zandwijk, N and Reid, G and George, AM}, title = {Zeolites ameliorate asbestos toxicity in a transgenic model of malignant mesothelioma.}, journal = {FASEB bioAdvances}, volume = {1}, number = {9}, pages = {550-560}, pmid = {32123850}, issn = {2573-9832}, abstract = {Malignant mesothelioma (MM) is an almost invariably fatal cancer caused by asbestos exposure. The toxicity of asbestos fibers is related to their physicochemical properties and the generation of free radicals. We set up a pilot study to investigate the potential of the zeolite clinoptilolite to counteract the asbestos carcinogenesis by preventing the generation of reactive nitrogen and oxygen radicals. In cell culture experiments, clinoptilolite prevented asbestos-induced cell death, reactive oxygen species production, DNA degradation, and overexpression of genes known to be up-regulated by asbestos. In an asbestos-induced transgenic mouse model of MM, mice were injected intraperitoneal injections with blue asbestos, with or without clinoptilolite, and monitored for 30 weeks. By the end of the trial all 13 mice injected with asbestos alone had reached humane end points, whereas only 7 of 29 mice receiving crocidolite and clinoptilolite reached a similar stage of disease. Post-mortem examination revealed pinpoint mesothelioma-like tumors in affected mice, and the absence of tumor formation in surviving mice. Interestingly, the macrophage clearance system, which was largely suppressed in asbestos-treated mice, exhibited evidence of increased phagocytosis in mice treated with asbestos and clinoptilolite. Our study suggests that inhibiting the asbestos-induced generation of reactive oxygen species and stimulating the macrophage system may represent a pathway to amelioration of asbestos-induced toxicity. Additional studies are warranted to explore the underlying mechanisms responsible for our observations.}, } @article {pmid32117755, year = {2020}, author = {Reid, G and Johnson, TG and van Zandwijk, N}, title = {Manipulating microRNAs for the Treatment of Malignant Pleural Mesothelioma: Past, Present and Future.}, journal = {Frontiers in oncology}, volume = {10}, number = {}, pages = {105}, pmid = {32117755}, issn = {2234-943X}, abstract = {microRNAs (miRNAs) are an important class of non-coding RNA that post-transcriptionally regulate the expression of most protein-coding genes. Their aberrant expression in tumors contributes to each of the hallmarks of cancer. In malignant pleural mesothelioma (MPM), in common with other tumor types, changes in miRNA expression are characterized by a global downregulation, although elevated levels of some miRNAs are also found. While an increasing number of miRNAs exhibit altered expression in MPM, relatively few have been functionally characterized. Of a growing number with tumor suppressor activity in vitro, miR-16, miR-193a, and miR-215 were also shown to have tumor suppressor activity in vivo. In the case of miR-16, the significant inhibitory effects on tumor growth following targeted delivery of miR-16-based mimics in a xenograft model was the basis for a successful phase I clinical trial. More recently overexpressed miRNAs with oncogenic activity have been described. Many of these changes in miRNA expression are related to the characteristic loss of tumor suppressor pathways in MPM tumors. In this review we will highlight the studies providing evidence for therapeutic effects of modulating microRNA levels in MPM, and discuss these results in the context of emerging approaches to miRNA-based therapy.}, } @article {pmid32117751, year = {2020}, author = {Testa, JR and Berns, A}, title = {Preclinical Models of Malignant Mesothelioma.}, journal = {Frontiers in oncology}, volume = {10}, number = {}, pages = {101}, pmid = {32117751}, issn = {2234-943X}, abstract = {Rodent models of malignant mesothelioma help facilitate the understanding of the biology of this highly lethal cancer and to develop and test new interventions. Introducing the same genetic lesions as found in human mesothelioma in mice results in tumors that show close resemblance with the human disease counterpart. This includes the extensive inflammatory responses that characterize human malignant mesothelioma. The relatively fast development of mesothelioma in mice when the appropriate combination of lesions is introduced, with or without exposure to asbestos, make the autochthonous models particularly useful for testing new treatment strategies in an immunocompetent setting, whereas Patient-Derived Xenograft models are particularly useful to assess effects of inter- and intra-tumor heterogeneity and human-specific features of mesothelioma. It is to be expected that new insights obtained by studying these experimental systems will lead to new more effective treatments for this devastating disease.}, } @article {pmid32114955, year = {2020}, author = {Kim, K and Ko, Y and Oh, H and Ha, M and Kang, J and Kwon, EJ and Kang, JW and Kim, Y and Heo, HJ and Kim, G and Kim, JW and Kim, YH}, title = {MicroRNA-98 is a prognostic factor for asbestos-induced mesothelioma.}, journal = {Journal of toxicology and environmental health. Part A}, volume = {83}, number = {3}, pages = {126-134}, doi = {10.1080/15287394.2020.1734891}, pmid = {32114955}, issn = {1528-7394}, mesh = {Aged ; Asbestos/*toxicity ; Biomarkers, Tumor ; Carcinogens/*toxicity ; Down-Regulation ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Male ; Mesothelioma/chemically induced/*diagnosis ; MicroRNAs/genetics/*metabolism ; Middle Aged ; }, abstract = {Malignant pleural mesothelioma (MPM) is a type of cancer characterized by a short survival time and poor prognosis. Malignant pleural mesothelioma is most frequently associated with exposure to asbestos and other elongated mineral fibers. The aim of this study was to examine molecular differences between asbestos-exposed and non-exposed MPM patients and assess prognostic significances of molecular factors. Clinical and genetic data were downloaded from Cancer Genome Atlas. To identify the molecular differences, Significant Analysis of Microarray method was used. Prognostic significances of differentially expressed genes were confirmed by using Kaplan-Meier curve with the Log-Rank test. Although mRNAs did not exhibit any significant differences between the two patient groups, nine miRNAs were found to be down-regulated in the asbestos-exposed group. The top five pathways most relevant to the selected miRNAs were extracted through pathway enrichment analysis. Survival analysis revealed that high expression of only hsa-miR-98 was significantly associated with poor prognosis in patients with asbestos-exposed MPM. Evidence suggests that management of the aggressiveness and progression of asbestos-induced MPM may require high levels of hsa-miR-98 due to its tumor-suppressive role. This study might be helpful in enhancing our understanding of the biological mechanisms underlying asbestos-induced MPM and for acquiring greater insights into targeted therapy.Abbreviations: FDR: false discovery rate; MM: malignant mesothelioma; MPM: malignant pleural mesothelioma; mRNA: messenger RNA; miRNA: microRNA; SAM: significance analysis of microarrays; TCGA: the cancer genome atlas.}, } @article {pmid32106829, year = {2020}, author = {Drevinskaite, M and Patasius, A and Kevlicius, L and Mickys, U and Smailyte, G}, title = {Malignant mesothelioma of the tunica vaginalis testis: a rare case and review of literature.}, journal = {BMC cancer}, volume = {20}, number = {1}, pages = {162}, pmid = {32106829}, issn = {1471-2407}, mesh = {Aged ; Antineoplastic Agents/*therapeutic use ; Biopsy ; Cisplatin/therapeutic use ; Deoxycytidine/analogs & derivatives/therapeutic use ; Disease Progression ; Fatal Outcome ; Humans ; Lung Neoplasms/complications/*diagnosis/therapy ; Lymphadenopathy ; Male ; Mesothelioma/complications/*diagnosis/therapy ; Mesothelioma, Malignant ; Orchiectomy ; Pemetrexed/therapeutic use ; Prognosis ; Testicular Hydrocele/etiology/*surgery ; Testicular Neoplasms/complications/*diagnosis/therapy ; Gemcitabine ; }, abstract = {BACKGROUND: Malignant mesothelioma of the tunica vaginalis is a rare tumour which comprises less than 1% of all mesotheliomas.

CASE PRESENTATION: 69-years old patient with painful hard mass and hydrocele in the right scrotum to whom a right hydrocelectomy was performed. Any history of scrotal trauma or exposure to asbestos was not present. Excisional biopsy revealed a multinodular tumour with focal areas of necrosis and infiltrative growth. According to morphological and immunohistochemical findings, diagnosis of malignant biphasic mesothelioma of the tunica vaginalis testis was made. Two months after hydrocelectomy, right inguinal orchidectomy was performed. Post-surgical whole body CT scan revealed paraaortic and pararenal lymphadenopathy, likely to be metastatic. Adjuvant treatment with 6 cycles of cisplatin and pemetrexed was applied. After 3 cycles of chemotherapy, CT scan showed progression and the treatment was changed to gemcitabine 1 month after.

CONCLUSIONS: Although malignant mesothelioma of the tunica vaginalis is a rare malignancy, it poses a diagnostic challenge which can mimic common inguinal or scrotal diseases such as hydrocele. Despite aggressive surgical procedures or adjuvant therapies, the prognosis remains poor.}, } @article {pmid32083805, year = {2020}, author = {Quetel, L and Meiller, C and Assié, JB and Blum, Y and Imbeaud, S and Montagne, F and Tranchant, R and de Wolf, J and Caruso, S and Copin, MC and Hofman, V and Gibault, L and Badoual, C and Pintilie, E and Hofman, P and Monnet, I and Scherpereel, A and Le Pimpec-Barthes, F and Zucman-Rossi, J and Jaurand, MC and Jean, D}, title = {Genetic alterations of malignant pleural mesothelioma: association with tumor heterogeneity and overall survival.}, journal = {Molecular oncology}, volume = {14}, number = {6}, pages = {1207-1223}, pmid = {32083805}, issn = {1878-0261}, mesh = {Adult ; Aged ; Aged, 80 and over ; Cell Line, Tumor ; Female ; *Genetic Heterogeneity ; Humans ; Kaplan-Meier Estimate ; Male ; Mesothelioma, Malignant/epidemiology/*genetics/pathology ; Middle Aged ; Mutation/genetics ; Pleural Neoplasms/epidemiology/*genetics/pathology ; Survival Analysis ; Young Adult ; }, abstract = {Development of precision medicine for malignant pleural mesothelioma (MPM) requires a deep knowledge of tumor heterogeneity. Histologic and molecular classifications and histo-molecular gradients have been proposed to describe heterogeneity, but a deeper understanding of gene mutations in the context of MPM heterogeneity is required and the associations between mutations and clinical data need to be refined. We characterized genetic alterations on one of the largest MPM series (266 tumor samples), well annotated with histologic, molecular and clinical data of patients. Targeted next-generation sequencing was performed focusing on the major MPM mutated genes and the TERT promoter. Molecular heterogeneity was characterized using predictors allowing classification of each tumor into the previously described molecular subtypes and the determination of the proportion of epithelioid-like and sarcomatoid-like components (E/S.scores). The mutation frequencies are consistent with literature data, but this study emphasized that TERT promoter, not considered by previous large sequencing studies, was the third locus most affected by mutations in MPM. Mutations in TERT promoter, NF2, and LATS2 were more frequent in nonepithelioid MPM and positively associated with the S.score. BAP1, NF2, TERT promoter, TP53, and SETD2 mutations were enriched in some molecular subtypes. NF2 mutation rate was higher in asbestos unexposed patient. TERT promoter, NF2, and TP53 mutations were associated with a poorer overall survival. Our findings lead to a better characterization of MPM heterogeneity by identifying new significant associations between mutational status and histologic and molecular heterogeneity. Strikingly, we highlight the strong association between new mutations and overall survival.}, } @article {pmid32082887, year = {2019}, author = {Döngel, İ and Akbaş, A and Benli, İ and Bayram, M}, title = {Comparison of serum biochemical markers in patients with mesothelioma and pleural plaques versus healthy individuals exposed to environmental asbestos.}, journal = {Turk gogus kalp damar cerrahisi dergisi}, volume = {27}, number = {3}, pages = {374-380}, pmid = {32082887}, issn = {1301-5680}, abstract = {BACKGROUND: In this study, we aimed to compare serum biochemical markers in patients with malignant pleural mesothelioma and pleural plaques versus healthy individuals exposed to environmental asbestos.

METHODS: Between September 01, 2010 and March 31, 2011, a total of 540 participants (354 males, 186 females; mean age 61.4 years; range, 35 to 89 years) were included in the study. The participants were divided into four groups as follows: (1) patients with pleural plaques (n=277); (2) healthy individuals with normal chest X-rays who were exposed to environmental asbestos (n=121); (3) healthy individuals with normal chest X-rays who were not exposed to environmental asbestos (n=118); and (4) patients with malignant pleural mesothelioma (n=24). Serum levels of carcinoembryonic antigen, cancer antigen 125, 15-3, 19-9, free T3, free T4, thyroidstimulating hormone, vitamin B12, folate, and ferritin were measured.

RESULTS: Serum cancer antigen 125, 15-3, folic acid, vitamin B12, and ferritin levels were higher with lower free T3 levels in Group 4 than the other groups. The areas under the curve for cancer antigen 125 and 15-3 were 0.78 and 0.67, respectively in the differential diagnosis of mesothelioma from other pathologies (p<0.001 for both). Optimal limits of these biomarkers were 13.63 and 18.43 ng/mL, respectively with 83% and 75% sensitivity and 69% and 48% specificity, respectively.

CONCLUSION: The combination or individual use of serum cancer antigen 125, 15-3, folic acid, vitamin B12, and ferritin levels may be helpful for early diagnosis and treatment of malignant pleural mesothelioma.}, } @article {pmid32081346, year = {2020}, author = {Sinha, S and Swift, AJ and Kamil, MA and Matthews, S and Bull, MJ and Fisher, P and De Fonseka, D and Saha, S and Edwards, JG and Johns, CS}, title = {The role of imaging in malignant pleural mesothelioma: an update after the 2018 BTS guidelines.}, journal = {Clinical radiology}, volume = {75}, number = {6}, pages = {423-432}, doi = {10.1016/j.crad.2019.12.001}, pmid = {32081346}, issn = {1365-229X}, support = {205188/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Diagnostic Imaging/*standards ; Early Detection of Cancer ; Humans ; Mesothelioma, Malignant/*diagnostic imaging/pathology ; Neoplasm Staging ; Pleural Neoplasms/*diagnostic imaging/pathology ; *Practice Guidelines as Topic ; Societies, Medical ; }, abstract = {Malignant pleural mesothelioma (MPM) is a primary malignancy of the pleura and is associated with a poor outcome. The symptoms and signs of malignant mesothelioma present late in the natural history of the disease and are non-specific, making the diagnosis challenging and imaging key. In 2018, the British Thoracic Society (BTS) updated the guideline on diagnosis, staging, and follow-up of patients with MPM. These recommendations are discussed in this review of the current literature on imaging of MPM. It is estimated MPM will continue to cause serious morbidity and mortality in the UK late into the 21st century, and internationally, people continue to be exposed to asbestos. We aim to update the reader on current and future imaging strategies, which could aid early diagnosis of pleural malignancy and provide an update on staging and assessment of tumour response.}, } @article {pmid32080953, year = {2020}, author = {Okazaki, Y and Misawa, N and Akatsuka, S and Kohyama, N and Sekido, Y and Takahashi, T and Toyokuni, S}, title = {Frequent homozygous deletion of Cdkn2a/2b in tremolite-induced malignant mesothelioma in rats.}, journal = {Cancer science}, volume = {111}, number = {4}, pages = {1180-1192}, pmid = {32080953}, issn = {1349-7006}, support = {JP17H04064 and JP19H05462//Japan Society for the Promotion of Science/ ; JP25860292//Japan Society for the Promotion of Science/ ; }, mesh = {Animals ; Asbestos/*toxicity ; Asbestos, Amphibole/toxicity ; Asbestos, Crocidolite/toxicity ; Asbestos, Serpentine/toxicity ; Comparative Genomic Hybridization ; Cyclin-Dependent Kinase Inhibitor p15/*genetics ; Cyclin-Dependent Kinase Inhibitor p16/*genetics ; Homozygote ; Humans ; Lung Neoplasms/chemically induced/*genetics/pathology ; Mesothelioma/chemically induced/*genetics/pathology ; Mesothelioma, Malignant ; Rats ; Risk Factors ; Sequence Deletion/genetics ; }, abstract = {The onset of malignant mesothelioma (MM) is linked to exposure to asbestos fibers. Asbestos fibers are classified as serpentine (chrysotile) or amphibole, which includes the crocidolite, amosite, anthophyllite, tremolite, and actinolite types. Although few studies have been undertaken, anthophyllite has been shown to be associated with mesothelioma, and tremolite, a contaminant in talc and chrysotile, is a risk factor for carcinogenicity. Here, after characterizing the length and width of these fibers by scanning electron microscopy, we explored the cytotoxicity induced by tremolite and anthophyllite in cells from an immortalized human mesothelial cell line (MeT5A), murine macrophages (RAW264.7), and in a rat model. Tremolite and short anthophyllite fibers were phagocytosed and localized to vacuoles, whereas the long anthophyllite fibers were caught on the pseudopod of the MeT5A and Raw 264.7 cells, according to transmission electron microscopy. The results from a 2-day time-lapse study revealed that tremolite was engulfed and damaged the MeT5A and RAW264.7 cells, but anthophyllite was not cytotoxic to these cells. Intraperitoneal injection of tremolite in rats induced diffuse serosal thickening, whereas anthophyllite formed focal fibrosis and granulomas on peritoneal serosal surfaces. Furthermore, the loss of Cdkn2a/2b, which are the most frequently lost foci in human MM, were observed in 8 cases of rat MM (homozygous deletion [5/8] and loss of heterozygosity [3/8]) by array-based comparative genomic hybridization techniques. These results indicate that tremolite initiates mesothelial injury and persistently frustrates phagocytes, causing subsequent peritoneal fibrosis and MM. The possible mechanisms of carcinogenicity based on fiber diameter/length are discussed.}, } @article {pmid32077824, year = {2020}, author = {Loreto, C and Lombardo, C and Caltabiano, R and Ledda, C and Hagnas, M and Filetti, V and Rapisarda, V}, title = {An In vivo Immunohistochemical Study on MacroH2A.1 in Lung and Lymph-Node Tissues Exposed to an Asbestiform Fiber.}, journal = {Current molecular medicine}, volume = {20}, number = {8}, pages = {653-660}, doi = {10.2174/1566524020666200220130023}, pmid = {32077824}, issn = {1875-5666}, mesh = {Animals ; Asbestos, Amphibole/*toxicity ; Histones/*metabolism ; Immunohistochemistry/*methods ; Lung/drug effects/*metabolism/pathology ; Lymph Nodes/drug effects/*metabolism/pathology ; Sheep ; }, abstract = {AIMS: The aim of this study was to investigate MacroH2A.1 immunoexpression in tissues of sheep exposed to FE.

BACKGROUND: The correlation between asbestiform fibers, lung cancer, pleural mesothelioma, and other lung diseases is already well established as the pathophisiological pathophysiological respiratory mechanisms involved by inhalation of Fluoro-edenite (FE). The latter is represented by cell proliferation and inducing the release of growth factors, cytokines, and reactive oxygen and nitrite species, with DNA damage that causes chronic inflammation and carcinogenesis. MacroH2A.1, and histone variant, seems to play a role in sensing the metabolic state of the cell and linking it with chromatin. Physiologically, MacroH2A.1 is expressed at low levels in stem cells and it became upregulated during differentiation, preventing reprogramming of induced pluripotent stem cells and after nuclear transfer. In particular, MacroH2A.1 has been shown to explicate a potent antitumor mechanism in vivo as it results upregulated in senescent cells determining a permanent growth-arrest.

OBJECTIVE: Evaluate the possible role of the histone variant in the organism in response to deep insight understanding the mechanisms of toxicity and the cellular response to FE.

METHODS: Lung and lymph nodes of exposed sheep were selected. Samples were processed for histological and immunihistochemical immunohistochemical evaluations. Densitometric, morphometric, and statistical analysis analyses were conducted.

RESULTS: Tissue sections of FE exposed sheep demonstrated overexpression of MacroH2A.1 vs unexposed samples. The data suggest an involvement of these this molecule in the cellular response triggered by FE directed exposure.

CONCLUSION: In this contest, MacroH2A.1 overexpression supports its function as an epigenetic stabilizer that helps to establish and maintain differentiated states.}, } @article {pmid32065212, year = {2020}, author = {Barbieri, PG and Somigliana, A and Chen, Y and Consonni, D and Vignola, R and Finotto, L}, title = {Lung Asbestos Fibre Burden and Pleural Mesothelioma in Women with Non-occupational Exposure.}, journal = {Annals of work exposures and health}, volume = {64}, number = {3}, pages = {297-310}, doi = {10.1093/annweh/wxaa009}, pmid = {32065212}, issn = {2398-7316}, mesh = {*Asbestos/adverse effects ; Autopsy ; Female ; Humans ; Lung ; *Mesothelioma/etiology ; Occupational Exposure ; *Pleural Neoplasms/etiology ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) due to environmental and familial (domestic) asbestos exposure is well recognized. However, information on cumulative asbestos dose in subjects affected by MPM is limited.

OBJECTIVES: To evaluate the residual lung asbestos fibre and asbestos body burden in women with MPM with past environmental and/or familial asbestos exposure.

METHODS: We collected lung samples from autopsies regarding 15 non-occupationally asbestos-exposed MPM cases, divided in three groups: (i) familial exposure from the Fincantieri shipyards in Monfalcone (No. 7), (ii) environmental and familial asbestos exposure from the asbestos-cement plant Fibronit in Broni (No. 6), and (iii) environmental exposure from the Fibronit plant (No. 2). Asbestos body (AB) and fibres (AF) per gram of dry lung tissue were counted by optical and scanning electron microscopy, respectively, and expressed as geometric means and standard deviations (GM, GSD).

RESULTS: GM/GSD of AB counts were 6123/9.6 (Group 1), 13 800/10.4 (Group 2), and 8400/1.1 (Group 3); GM/GSD of AF were 0.6/2.1 (Group 1), 7.9/2.1 (Group 2), and 6.0/2.3 (Group 3) million. Pleural plaques were observed in 12 cases.

CONCLUSIONS: Exclusive familial exposure to asbestos determined cumulative doses close to those observed in moderate occupational exposure circumstances. Our results also suggest that combined environmental and familial exposures may cause unexpectedly high cumulative fibre doses.}, } @article {pmid32054819, year = {2020}, author = {, }, title = {Global and regional burden of cancer in 2016 arising from occupational exposure to selected carcinogens: a systematic analysis for the Global Burden of Disease Study 2016.}, journal = {Occupational and environmental medicine}, volume = {77}, number = {3}, pages = {151-159}, pmid = {32054819}, issn = {1470-7926}, mesh = {Adolescent ; Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Carcinogens ; Disabled Persons/statistics & numerical data ; Female ; Global Burden of Disease/*statistics & numerical data/*trends ; Global Health/statistics & numerical data/trends ; Humans ; *Life Expectancy ; Lung Neoplasms/mortality ; Male ; Mesothelioma ; Mesothelioma, Malignant ; Middle Aged ; Neoplasms/*epidemiology/mortality ; Occupational Diseases/epidemiology ; Occupational Exposure/adverse effects/*statistics & numerical data ; Quality-Adjusted Life Years ; Risk Assessment ; Risk Factors ; Sex Distribution ; Socioeconomic Factors ; Young Adult ; }, abstract = {OBJECTIVES: This study provides a detailed analysis of the global and regional burden of cancer due to occupational carcinogens from the Global Burden of Disease 2016 study.

METHODS: The burden of cancer due to 14 International Agency for Research on Cancer Group 1 occupational carcinogens was estimated using the population attributable fraction, based on past population exposure prevalence and relative risks from the literature. The results were used to calculate attributable deaths and disability-adjusted life years (DALYs).

RESULTS: There were an estimated 349 000 (95% Uncertainty Interval 269 000 to 427 000) deaths and 7.2 (5.8 to 8.6) million DALYs in 2016 due to exposure to the included occupational carcinogens-3.9% (3.2% to 4.6%) of all cancer deaths and 3.4% (2.7% to 4.0%) of all cancer DALYs; 79% of deaths were of males and 88% were of people aged 55 -79 years. Lung cancer accounted for 86% of the deaths, mesothelioma for 7.9% and laryngeal cancer for 2.1%. Asbestos was responsible for the largest number of deaths due to occupational carcinogens (63%); other important risk factors were secondhand smoke (14%), silica (14%) and diesel engine exhaust (5%). The highest mortality rates were in high-income regions, largely due to asbestos-related cancers, whereas in other regions cancer deaths from secondhand smoke, silica and diesel engine exhaust were more prominent. From 1990 to 2016, there was a decrease in the rate for deaths (-10%) and DALYs (-15%) due to exposure to occupational carcinogens.

CONCLUSIONS: Work-related carcinogens are responsible for considerable disease burden worldwide. The results provide guidance for prevention and control initiatives.}, } @article {pmid32050546, year = {2020}, author = {Töreyin, ZN and Ghosh, M and Göksel, Ö and Göksel, T and Godderis, L}, title = {Exhaled Breath Analysis in Diagnosis of Malignant Pleural Mesothelioma: Systematic Review.}, journal = {International journal of environmental research and public health}, volume = {17}, number = {3}, pages = {}, pmid = {32050546}, issn = {1660-4601}, mesh = {*Asbestos ; *Biomarkers, Tumor/analysis ; *Breath Tests ; Exhalation ; Humans ; *Mesothelioma/diagnosis ; Prospective Studies ; *Volatile Organic Compounds ; }, abstract = {Malignant pleural mesothelioma (MPM) is mainly related to previous asbestos exposure. There is still dearth of information on non-invasive biomarkers to detect MPM at early stages. Human studies on exhaled breath biomarkers of cancer and asbestos-related diseases show encouraging results. The aim of this systematic review was to provide an overview on the current knowledge about exhaled breath analysis in MPM diagnosis. A systematic review was conducted on MEDLINE (PubMed), EMBASE and Web of Science databases to identify relevant studies. Quality assessment was done by the Newcastle-Ottawa Scale. Six studies were identified, all of which showed fair quality and explored volatile organic compounds (VOC) based breath profile using Gas Chromatography Coupled to Mass Spectrometry (GC-MS), Ion Mobility Spectrometry Coupled to Multi-capillary Columns (IMS-MCC) or pattern-recognition technologies. Sample sizes varied between 39 and 330. Some compounds (i.e, cyclohexane, P3, P5, P50, P71, diethyl ether, limonene, nonanal, VOC IK 1287) that can be indicative of MPM development in asbestos exposed population were identified with high diagnostic accuracy rates. E-nose studies reported breathprints being able to distinguish MPM from asbestos exposed individuals with high sensitivity and a negative predictive value. Small sample sizes and methodological diversities among studies limit the translation of results into clinical practice. More prospective studies with standardized methodologies should be conducted on larger populations.}, } @article {pmid32050285, year = {2020}, author = {Habbel, VSA and Mahler, EA and Feyerabend, B and Oldhafer, KJ and Lipp, MJ}, title = {[Diffuse malignant peritoneal mesothelioma (DMPM) - a rare diagnosis].}, journal = {Zeitschrift fur Gastroenterologie}, volume = {58}, number = {2}, pages = {146-151}, doi = {10.1055/a-1083-6962}, pmid = {32050285}, issn = {1439-7803}, mesh = {Antineoplastic Agents/*administration & dosage ; Antineoplastic Combined Chemotherapy Protocols ; Combined Modality Therapy ; *Cytoreduction Surgical Procedures/methods ; Female ; Humans ; Hyperthermia, Induced/*methods ; Male ; Mesothelioma/drug therapy/mortality/surgery/*therapy ; Peritoneal Neoplasms/drug therapy/mortality/surgery/*therapy ; Prognosis ; Survival Rate ; }, abstract = {Diffuse malignant peritoneal mesothelioma (DMPM) is a rare diagnosis, found more frequently in men than in women. Symptoms are unspecific abdominal disorders making that diagnosis difficult to set. Causes of DMPM are yet to be discovered in entirety. Asbestos exposure is the reason for approximately 7 % of all peritoneal mesotheliomas. Until the evaluation of systematic cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) DMPM was a fatal diagnosis with a median overall survival (OS) of 4-13 months. The prognosis of DMPM dramatically improved with implementation of CRS and HIPEC to an OS of 30-92 month nowadys. CRS and HIPEC were performed in this case.}, } @article {pmid32050148, year = {2020}, author = {Singh, R and Cherrie, JW and Rao, B and Asolekar, SR}, title = {Assessment of the future mesothelioma disease burden from past exposure to asbestos in ship recycling yards in India.}, journal = {International journal of hygiene and environmental health}, volume = {225}, number = {}, pages = {113478}, doi = {10.1016/j.ijheh.2020.113478}, pmid = {32050148}, issn = {1618-131X}, mesh = {Adult ; Air Pollutants, Occupational/*toxicity ; Asbestos/*toxicity ; Humans ; India ; Lung Neoplasms/*epidemiology/etiology ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Exposure/*adverse effects ; Recycling ; *Ships ; Young Adult ; }, abstract = {The recycling of end-of-life vessels is a complex activity that generates an enormous amount of hazardous waste, including asbestos-containing materials (ACM). Efforts by the Government of India to comply with national and international regulations and improved standard operating procedures are expected to lower the exposure risk of the workforce to hazardous substances, including asbestos. The current workers are likely to face lesser risks than did those exposed in the past. The present study assesses the health risks from past exposure of asbestos for those workers engaged in handling and removing ACM in ship recycling yards before environmentally sound recycling of obsolete ships was introduced in the early 2000s. Estimates were made of the number of workers exposed, and the intensity of exposure and these data were used to estimate the likely number of mesothelioma deaths in the future. It was estimated that nearly 15% of the total workforce engaged in ship recycling will suffer from mesothelioma which translates to about 4,513 mesothelioma deaths among the total of 31,000 workers estimated to be ever employed in the yards from 1994 till 2002. Recommendations are made for a practical approach to the safe handling of ACMs in Indian ship recycling yards.}, } @article {pmid32041759, year = {2020}, author = {Ahmed, ST and Barvo, M and Kamath, N and Alweis, R}, title = {Acute popliteal thrombus workup leads to discovery of primary peritoneal mesothelioma in the absence of any known asbestos exposure.}, journal = {BMJ case reports}, volume = {13}, number = {2}, pages = {}, pmid = {32041759}, issn = {1757-790X}, mesh = {Abdomen/diagnostic imaging ; Aged ; Antineoplastic Agents/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Asbestos ; Ascites/diagnostic imaging ; Biopsy, Large-Core Needle ; Carboplatin/therapeutic use ; Diagnosis, Differential ; Emergency Service, Hospital ; Humans ; Lung Neoplasms/*diagnosis/drug therapy ; Male ; Mesothelioma/*diagnosis/drug therapy ; Mesothelioma, Malignant ; Pelvis/diagnostic imaging ; Pemetrexed/therapeutic use ; Peritoneal Neoplasms/*diagnosis/drug therapy ; Popliteal Artery/surgery ; Positron Emission Tomography Computed Tomography ; Thrombosis/surgery ; }, abstract = {A 75-year-old man presented to the emergency department with 1-day history of right lower limb pain and 3-month history of vague abdominal pain. In the emergency department a thrombus was discovered in the right popliteal artery. CT scan of the abdomen and pelvis revealed high-density material in the pelvis, multiple hypodensities on the liver, ascites with omental nodularity, and high-density material along the stomach wall. He underwent thrombectomy and was started on anticoagulation therapy. The core needle biopsy revealed primary omental mesothelioma. There was no history of any known asbestos exposure. He also had to undergo therapeutic paracentesis twice due to abdominal distension. Mesothelioma treatment of carboplatin and pemetrexed was started, and the patient is currently receiving this chemotherapy treatment regimen.}, } @article {pmid32041124, year = {2020}, author = {Airoldi, C and Ferrante, D and Miligi, L and Piro, S and Stoppa, G and Migliore, E and Chellini, E and Romanelli, A and Sciacchitano, C and Mensi, C and Cavone, D and Romeo, E and Massari, S and Marinaccio, A and Magnani, C}, title = {Estimation of Occupational Exposure to Asbestos in Italy by the Linkage of Mesothelioma Registry (ReNaM) and National Insurance Archives. Methodology and Results.}, journal = {International journal of environmental research and public health}, volume = {17}, number = {3}, pages = {}, pmid = {32041124}, issn = {1660-4601}, mesh = {Asbestos/*adverse effects ; Humans ; Industry ; Italy ; Mesothelioma/*chemically induced ; National Health Programs ; Occupational Exposure/*adverse effects ; Registries ; }, abstract = {The identification and monitoring of occupational cancer is an important aspect of occupational health protection. The Italian law on the protection of workers (D. Leg. 81/2008) includes different cancer monitoring systems for high and low etiologic fraction tumors. Record linkage between cancer registries and administrative data is a convenient procedure for occupational cancer monitoring. We aim to: (i) Create a list of industries with asbestos exposure and (ii) identify cancer cases who worked in these industries. The Italian National Mesothelioma Registry (ReNaM) includes information on occupational asbestos exposure of malignant mesothelioma (MM) cases. We developed using data from seven Italian regions a methodology for listing the industries with potential exposure to asbestos linking ReNaM to Italian National Social Security Institute (INPS) data. The methodology is iterative and adjusts for imprecision and inaccuracy in reporting firm names at interview. The list of asbestos exposing firms was applied to the list of cancer cases (all types associated or possibly associated with asbestos according to International Agency for Research on Cancer (IARC) monograph 100C) in two Italian regions for the indication of possible asbestos exposure. Eighteen percent of the cancer cases showed at least one work period in firms potentially exposing to asbestos, 48% of which in regions different from where the cases lived at diagnosis. The methodology offers support for the preliminary screening of asbestos exposing firms in the occupational history of cancer cases.}, } @article {pmid32040984, year = {2020}, author = {Wylie, AG and Korchevskiy, A and Segrave, AM and Duane, A}, title = {Modeling mesothelioma risk factors from amphibole fiber dimensionality: mineralogical and epidemiological perspective.}, journal = {Journal of applied toxicology : JAT}, volume = {40}, number = {4}, pages = {515-524}, doi = {10.1002/jat.3923}, pmid = {32040984}, issn = {1099-1263}, mesh = {Aerosols ; Asbestos, Amphibole/*adverse effects/analysis ; Construction Materials/*adverse effects/analysis ; Humans ; Linear Models ; Mesothelioma/diagnosis/*epidemiology ; *Models, Theoretical ; Nonlinear Dynamics ; Occupational Exposure/*adverse effects ; Particle Size ; Risk Assessment ; Risk Factors ; }, abstract = {Amphiboles are common rock-forming minerals but when they form asbestos, they are known carcinogens. Mesothelioma mortality among miners and millers per the unit of asbestiform amphibole exposure varies significantly across cohorts when asbestos exposure measurements are based on the membrane filter method. Because the cohorts were exposed to different occurrences of asbestiform amphibole, variance in mesothelioma potency (RM) among cohorts is likely due to differences in exposure characteristics not reflected by the membrane filter method. In this paper using both linear and nonlinear models we correlate RM from four mining and milling cohorts with two-dimensional parameters of the exposure. The parameters are based on the proportion of elongated minerals that are >5 μm in length from each occurrence that also have either (a) width ≤ 0.15 μm, or (b) width ≤ 0.25 μm. Based on the models we derived, it was possible to quantify RM for the occurrences of asbestiform amphibole associated with mesothelioma excess but for which epidemiologically based RM has not been published. It was demonstrated that modeled RM for amphibole occurrences in nonasbestiform habits are lower (fibrous glaucophane) or not significant (cleavage fragments). The results of the study can be used in a risk assessment of elongated mineral particles and have implications for public policy and regulations.}, } @article {pmid32039010, year = {2019}, author = {Nicolini, F and Bocchini, M and Bronte, G and Delmonte, A and Guidoboni, M and Crinò, L and Mazza, M}, title = {Malignant Pleural Mesothelioma: State-of-the-Art on Current Therapies and Promises for the Future.}, journal = {Frontiers in oncology}, volume = {9}, number = {}, pages = {1519}, pmid = {32039010}, issn = {2234-943X}, abstract = {Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer of the pleural surface associated with asbestos exposure. The median survival of MPM patients is a mere 8-14 months, and there are few biomarkers and no cure available. It is hoped that, eventually, the incidence of MPM will drop and remain low and constant, given that most nations have banned the use of asbestos, but in the meantime, the incidence in Europe is still growing. The exact molecular mechanisms that explain the carcinogenicity of asbestos are not known. Standard therapeutic strategies for MPM include surgery, often coupled with chemotherapy and/or radiotherapy, in a small percentage of eligible patients and chemotherapy in tumors considered unresectable with or without adjuvant radiotherapy. In recent years, several new therapeutic avenues are being explored. These include angiogenesis inhibitors, synthetic lethal treatment, miRNA replacement, oncoviral therapies, and the fast-growing field of immunotherapy alone or in combination with chemotherapy. Of particular promise are the multiple options offered by immunotherapy: immune checkpoint inhibitors, tumor vaccines, and therapies taking advantage of tumor-specific antigens, such as specific therapeutic antibodies or advanced cell-based therapies exemplified by the CAR-T cells. This review comprehensively presents both old and new therapeutic options in MPM, focusing on the results of the numerous recent and on-going clinical trials in the field, including the latest data presented at international meetings (AACR, ASCO, and ESMO) this year, and concludes that more work has to be done in the framework of tailored therapies to identify reliable targets and novel biomarkers to impact MPM management.}, } @article {pmid32035500, year = {2020}, author = {Pais, A and Pinto, N and Cardoso, J and Fernandes, M and Coutinho, AI and Oliveira, AS and Carvalho, L and Bárbara, C}, title = {[Diffuse Intraparenchymal Mesothelioma: An Atypical Presentation].}, journal = {Acta medica portuguesa}, volume = {33}, number = {2}, pages = {143-146}, doi = {10.20344/amp.11406}, pmid = {32035500}, issn = {1646-0758}, mesh = {Asbestosis/*diagnosis ; Diagnosis, Differential ; Humans ; Male ; Mesothelioma, Malignant/*diagnosis ; Middle Aged ; Occupational Diseases/*diagnosis ; Pleural Neoplasms/*diagnosis ; }, abstract = {Pleural mesothelioma is a disease associated with exposure to asbestos. Although rare, it is the most common malignant pleural neoplasm. It is difficult to diagnose and it has a poor prognosis. We report the case of a 62-year-old male patient with a history of prolonged occupational exposure to asbestos, with dyspnea for minor exertion and productive cough, for several months. Imaging studies revealed extensive interstitial involvement with marked thickening of the interlobular and centrilobular septa and tenuous pleural involvement. Several differential diagnoses were considered such as, asbestosis, cryptogenic organizing pneumonia, desquamative interstitial pneumonia, pleuropulmonary metastases, and/or bronchopulmonary infection, but the histological and immunohistochemical results were compatible with pleural mesothelioma - a rare malignant neoplasm, with pleural origin, with a high mortality rate.}, } @article {pmid32033249, year = {2020}, author = {Aoki, K and Saito, N}, title = {Biocompatibility and Carcinogenicity of Carbon Nanotubes as Biomaterials.}, journal = {Nanomaterials (Basel, Switzerland)}, volume = {10}, number = {2}, pages = {}, pmid = {32033249}, issn = {2079-4991}, abstract = {With the development of nanotechnology in recent years, there have been concerns about the health effects of nanoparticles. Carbon nanotubes (CNTs) are fibrous nanoparticles with a micro-sized length and nano-sized diameter, which exhibit excellent physical properties and are widely studied for their potential application in medicine. However, asbestos has been historically shown to cause pleural malignant mesothelioma and lung cancer by inhalation exposure. Because carbon nanotubes are also fibrous nanotubes, some have raised concerns about its possible carcinogenicity. We have reported that there is no clear evidence of carcinogenicity by local and intravenous administration of multi-walled CNTs to cancer mice models. We firmly believe that CNTs can be a safe, new, and high-performance biomaterials by controlling its type, site of administration, and dosage.}, } @article {pmid32021524, year = {2020}, author = {Cheng, YY and Rath, EM and Linton, A and Yuen, ML and Takahashi, K and Lee, K}, title = {The Current Understanding Of Asbestos-Induced Epigenetic Changes Associated With Lung Cancer.}, journal = {Lung Cancer (Auckland, N.Z.)}, volume = {11}, number = {}, pages = {1-11}, pmid = {32021524}, issn = {1179-2728}, abstract = {Asbestos is a naturally occurring mineral consisting of extremely fine fibres that can become trapped in the lungs after inhalation. Occupational and environmental exposures to asbestos are linked to development of lung cancer and malignant mesothelioma, a cancer of the lining surrounding the lung. This review discusses the factors that are making asbestos-induced lung cancer a continuing problem, including the extensive historic use of asbestos and decades long latency between exposure and disease development. Genomic mutations of DNA nucleotides and gene rearrangements driving lung cancer are well-studied, with biomarkers and targeted therapies already in clinical use for some of these mutations. The genes involved in these mutation biomarkers and targeted therapies are also involved in epigenetic mechanisms and are discussed in this review as it is hoped that identification of epigenetic aberrations in these genes will enable the same gene biomarkers and targeted therapies to be used. Currently, understanding of how asbestos fibres trapped in the lungs leads to epigenetic changes and lung cancer is incomplete. It has been shown that oxidoreduction reactions on fibre surfaces generate reactive oxygen species (ROS) which in turn damage DNA, leading to genetic and epigenetic alterations that reduce the activity of tumour suppressor genes. Epigenetic DNA methylation changes associated with lung cancer are summarised in this review, and some of these changes will be due to asbestos exposure. So far, little research has been carried out to separate the asbestos driven epigenetic changes from those due to non-asbestos causes of lung cancer. Asbestos-associated lung cancers exhibit less methylation variability than lung cancers in general, and in a large proportion of samples variability has been found to be restricted to promoter regions. Epigenetic aberrations in cancer are proving to be promising biomarkers for diagnosing cancers. It is hoped that further understanding of epigenetic changes in lung cancer can result in useful asbestos-associated lung cancer biomarkers to guide treatment. Research is ongoing into the detection of lung cancer epigenetic alterations using non-invasive samples of blood and sputum. These efforts hold the promise of non-invasive cancer diagnosis in the future. Efforts to reverse epigenetic aberrations in lung cancer by epigenetic therapies are ongoing but have not yet yielded success.}, } @article {pmid32006662, year = {2020}, author = {Gaetani, S and Monaco, F and Alessandrini, F and Tagliabracci, A and Sabbatini, A and Bracci, M and Valentino, M and Neuzil, J and Amati, M and Santarelli, L and Tomasetti, M}, title = {Mechanism of miR-222 and miR-126 regulation and its role in asbestos-induced malignancy.}, journal = {The international journal of biochemistry & cell biology}, volume = {121}, number = {}, pages = {105700}, doi = {10.1016/j.biocel.2020.105700}, pmid = {32006662}, issn = {1878-5875}, mesh = {Aged ; Asbestos/*adverse effects ; Carcinogens/*chemistry ; Humans ; Lung Neoplasms/*genetics/pathology ; Male ; Mesothelioma/*genetics/pathology ; Mesothelioma, Malignant ; MicroRNAs/*metabolism ; }, abstract = {MiR-222 and miR-126 are associated with asbestos exposure and the ensuing malignancy, but the mechanism(s) of their regulation remain unclear. We evaluated the mechanism by which asbestos regulates miR-222 and miR-126 expression in the context of cancer etiology. An 'in vitro' model of carcinogen-induced cell transformation was used based on exposing bronchial epithelium BEAS-2B cells to three different carcinogens including asbestos. Involvement of the EGFR pathway and the role of epigenetics have been investigated in carcinogen-transformed cells and in malignant mesothelioma, a neoplastic disease associated with asbestos exposure. Increased expression of miR-222 and miR-126 were found in asbestos-transformed cells, but not in cells exposed to arsenic and chrome. Asbestos-mediated activation of the EGFR pathway and macrophages-induced inflammation resulted in miR-222 upregulation, which was reversed by EGFR inhibition. Conversely, asbestos-induced miR-126 expression was affected neither by EGFR modulation nor inflammation. Rather than methylation of the miR-126 host gene EGFL7, epigenetic mechanism involving DNMT1- and PARP1-mediated chromatin remodeling was found to upregulate of miR-126 in asbestos-exposed cells, while miR-126 was downregulated in malignant cells. Analysis of MM tissue supported the role of PARP1 in miR-126 regulation. Therefore, activation of the EGFR pathway and the PARP1-mediated epigenetic regulation both play a role in asbestos-induced miRNA expression, associated with in asbestos-induced carcinogenesis and tumor progression.}, } @article {pmid32005436, year = {2020}, author = {Fels Elliott, DR and Jones, KD}, title = {Diagnosis of Mesothelioma.}, journal = {Surgical pathology clinics}, volume = {13}, number = {1}, pages = {73-89}, doi = {10.1016/j.path.2019.10.001}, pmid = {32005436}, issn = {1875-9157}, mesh = {Biopsy ; Humans ; Lung/diagnostic imaging/pathology ; Lung Neoplasms/*diagnosis/diagnostic imaging/pathology ; Magnetic Resonance Imaging ; Mesothelioma/*diagnosis/diagnostic imaging/pathology ; Radiography ; Tomography, X-Ray Computed ; }, abstract = {Mesothelioma is a rare neoplasm that arises from mesothelial cells lining body cavities including the pleura, pericardium, peritoneum, and tunica vaginalis. Most malignant mesotheliomas occur in the chest and are frequently associated with a history of asbestos exposure. The diagnosis of malignant mesothelioma is challenging and fraught with pitfalls, particularly in small biopsies. This article highlights what the pathologist needs to know regarding the clinical and radiographic presentation of mesothelioma, histologic features including subtypes and variants, and recent advances in immunohistochemical markers and molecular testing.}, } @article {pmid32002299, year = {2020}, author = {Ma, S and Chee, J and Fear, VS and Forbes, CA and Boon, L and Dick, IM and Robinson, BWS and Creaney, J}, title = {Pre-treatment tumor neo-antigen responses in draining lymph nodes are infrequent but predict checkpoint blockade therapy outcome.}, journal = {Oncoimmunology}, volume = {9}, number = {1}, pages = {1684714}, pmid = {32002299}, issn = {2162-4011}, mesh = {Animals ; Antigens, Neoplasm/genetics ; *Cancer Vaccines ; Humans ; Immune Checkpoint Inhibitors/*pharmacology ; Intracellular Signaling Peptides and Proteins/genetics ; Lymph Nodes ; Mice ; *Neoplasms/genetics/therapy ; T-Lymphocytes, Cytotoxic ; }, abstract = {Immune checkpoint blockade (ICPB) is a powerfully effective cancer therapy in some patients. Tumor neo-antigens are likely main targets for attack but it is not clear which and how many tumor mutations in individual cancers are actually antigenic, with or without ICPB therapy and their role as neo-antigen vaccines or as predictors of ICPB responses. To examine this, we interrogated the immune response to tumor neo-antigens in a murine model in which the tumor is induced by a natural human carcinogen (i.e. asbestos) and mimics its human counterpart (i.e. mesothelioma). We identified and screened 33 candidate neo-antigens, and found T cell responses against one candidate in tumor-bearing animals, mutant UQCRC2. Interestingly, we found a high degree of inter-animal variation in the magnitude of neo-antigen responses in otherwise identical mice. ICPB therapy with Cytotoxic T-lymphocyte-associated protein (CTLA-4) and α-glucocorticoid-induced TNFR family related gene (GITR) in doses that induced tumor regression, increased the magnitude of responses and unmasked functional T cell responses against another neo-antigen, UNC45a. Importantly, the magnitude of the pre-treatment draining lymph node (dLN) response to UNC45a closely corresponded to ICPB therapy outcomes. Surprisingly however, boosting pre-treatment UNC45a-specific T cell numbers did not improve response rates to ICPB. These observations suggest a novel biomarker approach to the clinical prediction of ICPB response and have important implications for the development of neo-antigen vaccines.}, } @article {pmid32002298, year = {2020}, author = {Sneddon, S and Rive, CM and Ma, S and Dick, IM and Allcock, RJN and Brown, SD and Holt, RA and Watson, M and Leary, S and Lee, YCG and Robinson, BWS and Creaney, J}, title = {Identification of a CD8+ T-cell response to a predicted neoantigen in malignant mesothelioma.}, journal = {Oncoimmunology}, volume = {9}, number = {1}, pages = {1684713}, pmid = {32002298}, issn = {2162-4011}, mesh = {Antigens, Neoplasm/genetics ; CD8-Positive T-Lymphocytes/*immunology ; Humans ; Immunotherapy ; *Mesothelioma, Malignant/immunology ; Receptors, Cell Surface ; }, abstract = {Neoantigens present unique and specific targets for personalized cancer immunotherapy strategies. Given the low mutational burden yet immunotherapy responsiveness of malignant mesothelioma (MM) when compared to other carcinogen-induced malignancies, identifying candidate neoantigens and T cells that recognize them has been a challenge. We used pleural effusions to gain access to MM tumor cells as well as immune cells in order to characterize the tumor-immune interface in MM. We characterized the landscape of potential neoantigens from SNVs identified in 27 MM patients and performed whole transcriptome sequencing of cell populations from 18 patient-matched pleural effusions. IFNγ ELISpot was performed to detect a CD8+ T cell responses to predicted neoantigens in one patient. We detected a median of 68 (range 7-258) predicted neoantigens across the samples. Wild-type non-binding to mutant binding predicted neoantigens increased risk of death in a model adjusting for age, sex, smoking status, histology and treatment (HR: 33.22, CI: 2.55-433.02, p = .007). Gene expression analysis indicated a dynamic immune environment within the pleural effusions. TCR clonotypes increased with predicted neoantigen burden. A strong activated CD8+ T-cell response was identified for a predicted neoantigen produced by a spontaneous mutation in the ROBO3 gene. Despite the challenges associated with the identification of bonafide neoantigens, there is growing evidence that these molecular changes can provide an actionable target for personalized therapeutics in difficult to treat cancers. Our findings support the existence of candidate neoantigens in MM despite the low mutation burden of the tumor, and may present improved treatment opportunities for patients.}, } @article {pmid31977466, year = {2020}, author = {Fernández-Rodríguez, P and Martín-Marcuartu, JJ and Acevedo Báñez, I and Masero Carretero, JM and Jiménez-Hoyuela García, JM}, title = {99mTc-HDP Bone Scintigraphy, SPECT/CT, and 18F-FDG PET/CT Diagnosis Imaging of Incidental Pleural Mesothelioma in a Patient With Biochemical Recurrences of Prostate Cancer: Is it Really a Coincidence?.}, journal = {Clinical nuclear medicine}, volume = {45}, number = {3}, pages = {e148-e150}, doi = {10.1097/RLU.0000000000002908}, pmid = {31977466}, issn = {1536-0229}, mesh = {Aged ; Diphosphonates ; Fluorodeoxyglucose F18 ; Humans ; Lung Neoplasms/complications/*diagnostic imaging ; Male ; Mesothelioma/complications/*diagnostic imaging ; Mesothelioma, Malignant ; Organotechnetium Compounds ; Pleural Neoplasms/complications/*diagnostic imaging ; *Positron Emission Tomography Computed Tomography ; Prostatic Neoplasms/blood/*complications ; Radiopharmaceuticals ; *Single Photon Emission Computed Tomography Computed Tomography ; }, abstract = {We present the case of a 69-year-old man with history of prostate carcinoma treated with prostatectomy and subsequently with external beam radiotherapy and hormone therapy because of biochemical recurrences. More than 10 years after the diagnosis, follow-up Tc-HDP bone scans and SPECT/CT images demonstrated an incidental diagnosis of osteoblastic pleural plaques that quickly evolve to mesothelioma. PET/CT achieved the definitive diagnosis by guiding the biopsy to the highest and most accessible focus of glucidic hypermetabolism. Our case report raises the association between prostate cancer patients treated with external beam radiotherapy and the development of pleural mesothelioma despite having no history of exposure to asbestos.}, } @article {pmid31967100, year = {2019}, author = {Vimercati, L and Cavone, D and Mansi, F and Cannone, ESS and DE Maria, L and Caputi, A and Delfino, MC and Serio, G}, title = {Health impact of exposure to asbestos in polluted area of Southern Italy.}, journal = {Journal of preventive medicine and hygiene}, volume = {60}, number = {4}, pages = {E407-E418}, pmid = {31967100}, issn = {2421-4248}, mesh = {*Asbestos ; Asbestosis/epidemiology/*mortality ; Cardiovascular Diseases/mortality ; Cause of Death ; *Environmental Exposure ; *Environmental Pollution ; Humans ; Italy/epidemiology ; Lung Neoplasms/epidemiology/mortality ; Mesothelioma/epidemiology/*mortality ; Neoplasms/epidemiology/mortality ; *Occupational Exposure ; Peritoneal Neoplasms/epidemiology/mortality ; Personal Protective Equipment ; Pleural Neoplasms/epidemiology/*mortality ; }, abstract = {The three main sources of asbestos pollution in the city of Bari, Puglia, the former Fibronit asbestos factory, the Torre Quetta beach, the former Rossani barracks and the history of their reclamation are described. The results of cohort studies on factory workers and case-control studies on asbestos exposure to the resident population and the onset of mesothelioma are also reported. Finally, the data of the regional register of mesothelioma related to residents in the city of Bari and four new cases with environmental exposure due to the former Rossani barracks are presented.}, } @article {pmid31965908, year = {2019}, author = {Peterson, MK and Mohar, I and Lam, T and Cook, TJ and Engel, AM and Lynch, H}, title = {Critical review of the evidence for a causal association between exposure to asbestos and esophageal cancer.}, journal = {Critical reviews in toxicology}, volume = {49}, number = {7}, pages = {597-613}, doi = {10.1080/10408444.2019.1692190}, pmid = {31965908}, issn = {1547-6898}, mesh = {Animals ; *Asbestos ; Environmental Exposure/*statistics & numerical data ; Esophageal Neoplasms/*epidemiology ; *Hazardous Substances ; Humans ; }, abstract = {Esophageal cancers comprise about 1% of all cancers diagnosed in the US but are more prevalent in other regions of the world. Several regulatory agencies have classified asbestos as a known human carcinogen, and it is linked to multiple diseases and malignancies, including lung cancer and mesothelioma. In a 2006 review of the epidemiological literature, the Institute of Medicine (IOM) did not find sufficient evidence to demonstrate a causal relationship between asbestos exposure and esophageal cancer. To reevaluate this conclusion, we performed a critical review of the animal toxicological, epidemiological, and mechanism of action literature on esophageal cancer and asbestos, incorporating studies published since 2006. Although there is some evidence in the epidemiological literature for an increased risk of esophageal cancer in asbestos-exposed occupational cohorts, these studies generally did not control for critical esophageal cancer risk factors (e.g. smoking, alcohol consumption). Furthermore, data from animal toxicological studies do not indicate that asbestos exposure increases esophageal cancer risk. Based on our evaluation of the literature, and reaffirming the IOM's findings, we conclude that there is insufficient evidence to demonstrate a causal link between asbestos exposure and esophageal cancer.}, } @article {pmid31963601, year = {2020}, author = {Oddone, E and Bollon, J and Nava, CR and Bugani, M and Consonni, D and Marinaccio, A and Magnani, C and Barone-Adesi, F}, title = {Predictions of Mortality from Pleural Mesothelioma in Italy After the Ban of Asbestos Use.}, journal = {International journal of environmental research and public health}, volume = {17}, number = {2}, pages = {}, pmid = {31963601}, issn = {1660-4601}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Epidemics/*statistics & numerical data ; Female ; Forecasting ; Humans ; Italy/epidemiology ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; Mesothelioma, Malignant ; Middle Aged ; }, abstract = {Even if the epidemic of malignant pleural mesothelioma (MPM) is still far from being over worldwide, the health effects of regulations banning asbestos can be evaluated in the countries that implemented them early. Estimates of MPM future burden can be useful to inform and support the implementation of anti-asbestos health policies all around the world. With this aim we described the trends of MPM deaths in Italy (1970-2014) and predicted the future number of cases in both sexes (2015-2039), with consideration of the national asbestos ban that was issued in 1992. The Italian National Statistical Institute (ISTAT) provided MPM mortality figures. Cases ranging from 25 to 89 years of age were included in the analysis. For each five-year period from 1970 to 2014, mortality rates were calculated and age-period-cohort Poisson models were used to predict future burden of MPM cases until 2039. During the period 1970-2014 a total number of 28,907 MPM deaths were observed. MPM deaths increased constantly over the study period, ranging from 1356 cases in 1970-1974 to 5844 cases in 2010-2014. The peak of MPM cases is expected to be reached in the period 2020-2024 (about 7000 cases). The decrease will be slow: about 26,000 MPM cases are expected to occur in Italy during the next 20 years (2020-2039). The MPM epidemic in Italy is far from being concluded despite the national ban implemented in 1992, and the peak is expected in 2020-2024, in both sexes. Our results are consistent with international literature.}, } @article {pmid31929796, year = {2019}, author = {Borchert, S and Suckrau, PM and Wessolly, M and Mairinger, E and Hegedus, B and Hager, T and Herold, T and Eberhardt, WEE and Wohlschlaeger, J and Aigner, C and Bankfalvi, A and Schmid, KW and Walter, RFH and Mairinger, FD}, title = {Screening of Pleural Mesothelioma Cell Lines for Kinase Activity May Identify New Mechanisms of Therapy Resistance in Patients Receiving Platin-Based Chemotherapy.}, journal = {Journal of oncology}, volume = {2019}, number = {}, pages = {2902985}, pmid = {31929796}, issn = {1687-8450}, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare, predominantly asbestos-related and biologically highly aggressive tumor associated with a dismal prognosis. Multimodal therapy consisting of platinum-based chemotherapy is the treatment of choice. The reasons underlying the rather poor efficacy of platinum compounds remain largely unknown. Kinase activity might influence cellular response to these regimens.

MATERIALS AND METHODS: For this exploratory study, we screened MPM cell lines (NCI-H2452, NCI-H2052, and MSTO-211H) differing in response to cisplatin and benign control fibroblasts (MRC-5) for overall phosphorylation patterns as well as kinase activity with respect to cellular response to cisplatin-based therapeutics. We analysed the cell lines for cellular kinases in a high-throughput manner using the highly innovative technique PamGene. Cell state analysis including apoptosis, necrosis, and cell viability was performed by using enzyme activity and fluorescent-based assays.

RESULTS: Cisplatin alters cellular phosphorylation patterns affecting cell cycle, migration, adhesion, signal transduction, immune modulation, and apoptosis. In cisplatin-responsive cell lines, phosphorylation of AKT1 and GSK3B was decreased but could not be influenced in cisplatin-resistant NCI-H2452 cells. Cisplatin-responsive cell lines showed increased phosphorylation levels of JNK1/2/3 but decreased phosphorylation in cisplatin-resistant NCI-H2452 cells.

CONCLUSION: Kinase phosphorylation and activity might play a crucial role in cellular response to cytostatic agents. Cisplatin influences phosphorylation patterns with distinct features in cisplatin-resistant cells. These alterations exert a significant impact on cell cycle, migration, adhesion, signal transduction, immune modulation, and apoptosis of the respective tumor cells. Based on our results, the induction of p38 or JNK1/3, or inhibition of AKT1 by, for example, BIA-6, might offer a positive synergistic effect by induction of an apoptotic response to cisplatin-based treatment, thus potentially enhancing the clinical outcome of MPM patients.}, } @article {pmid31927297, year = {2020}, author = {Cox, LA}, title = {Nonlinear dose-time-response functions and health-protective exposure limits for inflammation-mediated diseases.}, journal = {Environmental research}, volume = {182}, number = {}, pages = {109026}, doi = {10.1016/j.envres.2019.109026}, pmid = {31927297}, issn = {1096-0953}, mesh = {*Asbestos/toxicity ; Humans ; Inflammation ; Inhalation Exposure ; *Mesothelioma ; *Occupational Exposure ; *Occupational Health ; *Silicon Dioxide/toxicity ; Threshold Limit Values ; United States ; }, abstract = {Why have occupational safety regulations in the United States not been more successful in protecting worker health from mesothelioma risks, while apparently succeeding relatively well in reducing silicosis risks? This paper briefly discusses biological bases for thresholds and nonlinearities in exposure-response functions for respirable crystalline silica (RCS) and asbestos, based on modeling a chronic inflammation mode of action (mediated by activation of the NLRP3 inflammasome, for both RCS and asbestos). It applies previously published physiologically based pharmacokinetic (PBPK) models to perform computational experiments illuminating how different time courses of exposure with the same time-weighted average (TWA) concentration affect internal doses in target tissues (lung for RCS and mesothelium for asbestos). Key conclusions are that (i) For RCS, but not asbestos, limiting average (TWA) exposure concentrations also tightly constrains internal doses and ability to trigger chronic inflammation and resulting increases in disease risks (ii) For asbestos, excursions (i.e., spikes in concentrations); and especially the times between them are crucial drivers of internal doses and time until chronic inflammation; and hence (iii) These dynamic aspects of exposure, which are not addressed by current occupational safety regulations, should be constrained to better protect worker health. Adjusting permissible average exposure concentration limits (PELs) and daily excursion limits (ELs) is predicted to have little impact on reducing mesothelioma risks, but increasing the number of days between successive excursions is predicted to be relatively effective in reducing worker risks, even if it has little or no impact on TWA average concentrations.}, } @article {pmid31921422, year = {2020}, author = {Kim, MK and Kim, HW and Jang, M and Oh, SS and Yong, SJ and Jeong, Y and Jung, SH and Choi, JW}, title = {LOX family and ZFPM2 as novel diagnostic biomarkers for malignant pleural mesothelioma.}, journal = {Biomarker research}, volume = {8}, number = {}, pages = {1}, pmid = {31921422}, issn = {2050-7771}, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer that develops in the pleural and outer layer of tissues surrounding the lungs. MPM is primarily caused by occupational exposure to asbestos and results in a poor prognosis. Effective therapeutics as well as early diagnostics for the MPM are still lacking. To identify potential diagnostic biomarkers for MPM, we performed bioinformatics analysis of public database.

METHODS: Utilizing databases from Cancer Cell Line Encyclopedia (CCLE) and Gene Expression Omnibus (GEO), we identified several potential candidates that could act as MPM biomarkers. We carried out additional molecular analyses of these potential markers using MPM patient tissue samples via quantitative polymerase chain reaction.

RESULTS: We identified Lysyl oxidase (LOX), Lysyl oxidase homologs 1&2 (LOXL1& LOXL2) Zinc Finger Protein, FOG Family Member 2 (ZFPM2) as potential diagnostic biomarkers for MPM. In this study, we found that the LOX family and ZFPM2 showed comparable diagnostic ability to Fibulin-3 or mesothelin (MSLN) and would be better potential biomarkers than Sulfatase 1 (SULF1), Thrombospondin 2 (THBS2) and Cadherin 11 (CDH11).

CONCLUSIONS: LOX family and ZPFM2 were identified as novel MPM diagnostic biomarkers which could strengthen MPM clinical diagnostic capabilities.}, } @article {pmid31917456, year = {2020}, author = {Ugelvig Petersen, K and Pukkala, E and Martinsen, JI and Lynge, E and Tryggvadottir, L and Weiderpass, E and Kjærheim, K and Heikkinen, S and Hansen, J}, title = {Cancer incidence among seafarers and fishermen in the Nordic countries.}, journal = {Scandinavian journal of work, environment & health}, volume = {46}, number = {5}, pages = {461-468}, pmid = {31917456}, issn = {1795-990X}, mesh = {Adult ; Aged ; Humans ; Incidence ; Male ; Middle Aged ; Naval Medicine/*statistics & numerical data ; Neoplasms/*epidemiology ; Occupational Diseases/*epidemiology ; Scandinavian and Nordic Countries/epidemiology ; }, abstract = {Objectives Maritime workers may be exposed to several occupational hazards at sea. The aim of this study was to assess cancer incidence among seafarers and fishermen in the Nordic countries and identify patterns in morbidity in the context of existing studies in this field. Methods A cohort of 81 740 male seafarers and 66 926 male fishermen was established from census data on 15 million citizens in the five Nordic countries. Using personal identity codes, information on vital status and cancer was linked to members of the cohort from the national population and cancer registries for the follow-up period 1961-2005. Standardized incidence ratios (SIR) were calculated applying national cancer incidence rates for each country and pooling results. Results The overall incidence of cancer was increased among the male seafarers [SIR 1.22, 95% confidence interval (CI) 1.19-1.23]. Significant excesses were observed for multiple cancer sites among the seafarers, while results for the fishermen were mixed. Lip cancer incidence was increased among both maritime populations. For mesothelioma (SIR 2.17, 95% CI 1.83-2.56 seafarers) and non-melanoma skin cancer (SIR 1.23, 95% CI 1.14-1.32 seafarers), incidence was increased among the seafarers. Conclusion In our cohort, seafaring was associated with a higher overall incidence of cancer compared to the general population. While the majority of cancers could not be linked to specific occupational factors, increases in mesothelioma, lip and non-melanoma-skin cancer indicate previous exposure to asbestos, ultraviolet radiation and potentially also chemicals with dermal carcinogenic properties at sea.}, } @article {pmid31916469, year = {2020}, author = {Dodson, RF and Poye, LW}, title = {Tissue burden evaluation of elongated mineral particles in two individuals with mesothelioma and whose work history included manufacturing tile.}, journal = {Ultrastructural pathology}, volume = {44}, number = {1}, pages = {17-31}, doi = {10.1080/01913123.2019.1709935}, pmid = {31916469}, issn = {1521-0758}, mesh = {Asbestos, Amphibole/adverse effects/*analysis ; Humans ; Male ; Mesothelioma, Malignant/*etiology ; Middle Aged ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*etiology ; Talc/adverse effects/*agonists ; }, abstract = {Two cases with diagnosis of mesothelioma were referred to our laboratories with a request for tissue burden analysis in order to determine the presence of ferruginous bodies and uncoated elongated mineral particles in tissue samples. The individuals shared in common a past background of working in tile manufacturing facilities where industrial talc was used in the production of the products. Both were found to have ferruginous bodies in their lung tissues as well as elongated talc fibers/ribbons and elevated numbers of noncommercial amphiboles in their tissues. To our knowledge, this is the first report of tissue assessment for the presence of elongated mineral particles in individuals whose exposures to talc occurred were while working in the manufacture of tile products and who developed the fiber-related cancer - mesothelioma.}, } @article {pmid31905913, year = {2019}, author = {Klebe, S and Leigh, J and Henderson, DW and Nurminen, M}, title = {Asbestos, Smoking and Lung Cancer: An Update.}, journal = {International journal of environmental research and public health}, volume = {17}, number = {1}, pages = {}, pmid = {31905913}, issn = {1660-4601}, mesh = {Animals ; Asbestos/*adverse effects ; Humans ; Lung Neoplasms/*chemically induced ; Mesothelioma/*chemically induced ; Occupational Exposure ; Tobacco Smoking/*adverse effects ; }, abstract = {This review updates the scientific literature concerning asbestos and lung cancer, emphasizing cumulative exposure and synergism between asbestos exposure and tobacco smoke, and proposes an evidence-based and equitable approach to compensation for asbestos-related lung cancer cases. This update is based on several earlier reviews written by the second and third authors on asbestos and lung cancer since 1995. We reevaluated the peer-reviewed epidemiologic studies. In addition, selected in vivo and in vitro animal studies and molecular and cellular studies in humans were included. We conclude that the mechanism of lung cancer causation induced by the interdependent coaction of asbestos fibers and tobacco smoke at a biological level is a multistage stochastic process with both agents acting conjointly at all times. The new knowledge gained through this review provides the evidence for synergism between asbestos exposure and tobacco smoke in lung cancer causation at a biological level. The evaluated statistical data conform best to a multiplicative model for the interaction effects of asbestos and smoking on the lung cancer risk, with no requirement for asbestosis. Any asbestos exposure, even in a heavy smoker, contributes to causation. Based on this information, we propose criteria for the attribution of lung cancer to asbestos in smokers and non-smokers.}, } @article {pmid31905042, year = {2019}, author = {Cox, LA}, title = {Dose-response modeling of NLRP3 inflammasome-mediated diseases: asbestos, lung cancer, and malignant mesothelioma as examples.}, journal = {Critical reviews in toxicology}, volume = {49}, number = {7}, pages = {614-635}, doi = {10.1080/10408444.2019.1692779}, pmid = {31905042}, issn = {1547-6898}, mesh = {*Asbestos ; Carcinogens, Environmental ; *Dose-Response Relationship, Drug ; Environmental Exposure/*statistics & numerical data ; Humans ; Inflammasomes ; Inflammation ; Lung Neoplasms/*metabolism ; Mesothelioma/*metabolism ; Mesothelioma, Malignant ; NLR Family, Pyrin Domain-Containing 3 Protein/*metabolism ; Risk Assessment ; }, abstract = {Can a single fiber of amphibole asbestos increase the risk of lung cancer or malignant mesothelioma (MM)? Traditional linear no-threshold (LNT) risk assessment assumptions imply that the answer is yes: there is no safe exposure level. This paper draws on recent scientific progress in inflammation biology, especially elucidation of the activation thresholds for NLRP3 inflammasomes and resulting chronic inflammation, to model dose-response relationships for malignant mesothelioma and lung cancer risks caused by asbestos exposures. The modeling integrates a physiologically based pharmacokinetics (PBPK) front end with inflammation-driven two-stage clonal expansion (I-TSCE) models of carcinogenesis to describe how exposure leads to chronic inflammation, which in turn promotes carcinogenesis. Together, the combined PBPK and I-TSCE modeling predict that there are practical thresholds for exposure concentration below which asbestos exposure does not cause chronic inflammation in less than a lifetime, and therefore does not increase chronic inflammation-dependent cancer risks. Quantitative examples using model parameter estimates drawn from the literature suggest that practical thresholds may be within about a factor of 2 of some past exposure levels for some workers. The I-TSCE modeling framework explains previous puzzling aspects of asbestos epidemiology, such as why age at first exposure is a better predictor of lifetime MM risk than exposure duration. It may be a valuable tool for risk analysts when LNT assumptions are not justified due to inflammation response thresholds mediating dose-response relationships.}, } @article {pmid31904012, year = {2019}, author = {Colin, DJ and Bejuy, O and Germain, S and Triponez, F and Serre-Beinier, V}, title = {Implantation and Monitoring by PET/CT of an Orthotopic Model of Human Pleural Mesothelioma in Athymic Mice.}, journal = {Journal of visualized experiments : JoVE}, volume = {}, number = {154}, pages = {}, doi = {10.3791/60272}, pmid = {31904012}, issn = {1940-087X}, mesh = {Animals ; Cell Line, Tumor ; Cell Proliferation ; Fluorodeoxyglucose F18/chemistry ; Humans ; Lung Neoplasms/*diagnostic imaging/metabolism/pathology ; Mesothelioma/*diagnostic imaging/metabolism/pathology ; Mesothelioma, Malignant ; Mice, Nude ; Organ Size ; Pleural Neoplasms/*diagnostic imaging/metabolism/pathology ; *Positron Emission Tomography Computed Tomography ; *Xenograft Model Antitumor Assays ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor arising in the mesothelium that covers the lungs, the heart, and the thoracic cavity. MPM development is mainly associated with asbestos. Treatments provide only modest survival since the median survival average is 9-18 months from the time of diagnosis. Therefore, more effective treatments must be identified. Most data describing new therapeutic targets were obtained from in vitro experiments and need to be validated in reliable in vivo preclinical models. This article describes one such reliable MPM orthotopic model obtained after injection of a human MPM cell line H2052/484 into the pleural cavity of immunodeficient athymic mice. Transplantation in the orthotopic site allows studying the progression of tumor in the natural in vivo environment. Positron emission tomography/computed tomography (PET/CT) molecular imaging using the clinical [[18]F]-2-fluoro-2-deoxy-D-glucose ([[18]F]FDG) radiotracer is the diagnosis method of choice for examining patients with MPM. Accordingly, [[18]F]FDG-PET/CT was used to longitudinally monitor the disease progression of the H2052/484 orthotopic model. This technique has a high 3R potential (Reduce the number of animals, Refine to lessen pain and discomfort, and Replace animal experimentation with alternatives) since the tumor development can be monitored non-invasively and the number of animals required could be significantly reduced. This model displays a high development rate, a rapid tumor growth, is cost-efficient and allows for rapid clinical translation. By using this orthotopic xenograft MPM model, researchers can assess biological responses of a reliable MPM model following therapeutic interventions.}, } @article {pmid31901768, year = {2020}, author = {Lam, WS and Creaney, J and Chen, FK and Chin, WL and Muruganandan, S and Arunachalam, S and Attia, MS and Read, C and Murray, K and Millward, M and Spiro, J and Chakera, A and Gary Lee, YC and Nowak, AK}, title = {A phase II trial of single oral FGF inhibitor, AZD4547, as second or third line therapy in malignant pleural mesothelioma.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {140}, number = {}, pages = {87-92}, doi = {10.1016/j.lungcan.2019.12.018}, pmid = {31901768}, issn = {1872-8332}, mesh = {Aged ; Aged, 80 and over ; Antineoplastic Agents/*therapeutic use ; Benzamides/*therapeutic use ; Female ; Fibroblast Growth Factors/*antagonists & inhibitors ; Follow-Up Studies ; Humans ; Male ; Mesothelioma, Malignant/*drug therapy/metabolism/pathology ; Middle Aged ; Piperazines/*therapeutic use ; Pleural Neoplasms/*drug therapy/metabolism/pathology ; Prognosis ; Pyrazoles/*therapeutic use ; *Salvage Therapy ; Survival Rate ; }, abstract = {OBJECTIVES: Currently, there is no optimal salvage therapy for patients with malignant pleural mesothelioma (MPM) who relapse after treatment with first-line chemotherapy. In line with the strong preclinical rationale for targeting fibroblast growth factor receptor (FGFR) signalling in malignant mesothelioma, we conducted a phase II study assessing the efficacy of AZD4547, an oral tyrosine multi-kinase FGFR 1-3 inhibitor, as a second or third-line treatment.

MATERIALS AND METHODS: We conducted a single-center, open-label, single-arm phase II study of AZD4547 in eligible patients with confirmed, measurable MPM and radiological progression after first or second-line systemic chemotherapy. Patients received continuous, twice-daily oral AZD4547 on a 3-weekly cycle. The primary end point was 6-month progression free survival (PFS6). Response was assessed with CT scan every 6 weeks according to the modified RECIST criteria for mesothelioma (mRECIST) and toxicities were also assessed. The study used a Simon's two-stage design: 26 patients would be recruited to the first stage and more than 7 (27 %) of 26 patients were required to achieve PFS6 to continue to stage two, for a potential total cohort of 55 patients.

RESULTS: 3 of 24 patients (12 %) were progression-free at 6 months. Hence, the study fulfilled stopping criteria regardless of further recruitment and warranted discontinuation. The most common toxicities (across all grades) were hyperphosphatemia, xerostomia, mucositis, retinopathy, dysgeusia, and fatigue. Maximum toxicities were grade 2 or below for all patients across all cycles. There was no association between tumour BAP1 protein loss and clinical outcomes.

CONCLUSIONS: The FGFR 1-3 inhibitor AZD4547 did not demonstrate efficacy in patients with MPM who had progressed after first line treatment with platinum-based chemotherapy.}, } @article {pmid31900296, year = {2020}, author = {Hinkamp, CA and Dalal, SN and Butt, Y and Cabo Chan, AV}, title = {Diffuse epithelioid malignant mesothelioma of the pleura presenting as a hydropneumothorax and vertebral body invasion.}, journal = {BMJ case reports}, volume = {13}, number = {1}, pages = {}, pmid = {31900296}, issn = {1757-790X}, mesh = {Aged ; Asbestos/*adverse effects ; Diagnosis, Differential ; Humans ; Hydropneumothorax/*surgery ; Lung Neoplasms/*therapy ; Male ; Mesothelioma/*therapy ; Mesothelioma, Malignant ; Neoplasm Invasiveness ; Pleural Neoplasms/*therapy ; Thoracic Neoplasms/secondary/*therapy ; }, abstract = {Malignant mesothelioma is an uncommon form of neoplastic transformation of the mesothelial cells that line the serosal surfaces of the body. It most commonly affects the pleura and is often associated with pleural effusions and pleural-based masses. The annual incidence in the United States is only 3300 cases, representing less than 0.3% of all cancers worldwide, although this is likely underestimated. We present a case of diffuse epithelioid malignant pleural mesothelioma in a patient with remote, short-term asbestos exposure complicated by recurrent left-sided hydropneumothoraces and pleural-based invasion of the T12 vertebral body, which represent two rare coexisting complications. This case illustrates the importance of maintaining a broad differential for hydropneumothorax, particularly as the risk factors may be decades removed and the degree of asbestos exposure to induce a malignant mesothelioma may be smaller than has been traditionally thought.}, } @article {pmid31895128, year = {2020}, author = {Walters, GI}, title = {Occupational exposures and idiopathic pulmonary fibrosis.}, journal = {Current opinion in allergy and clinical immunology}, volume = {20}, number = {2}, pages = {103-111}, pmid = {31895128}, issn = {1473-6322}, mesh = {*Cost of Illness ; Dust ; Humans ; Idiopathic Pulmonary Fibrosis/*epidemiology/etiology/prevention & control ; Incidence ; Inhalation Exposure/adverse effects ; Meta-Analysis as Topic ; Occupational Diseases/*epidemiology/etiology/prevention & control ; Occupational Exposure/*adverse effects/prevention & control ; Prevalence ; Risk Factors ; }, abstract = {PURPOSE OF REVIEW: A recent meta-analysis of data from international case-control studies reports a population attributable fraction of 16% for occupational factors in the cause of idiopathic pulmonary fibrosis (IPF). Smoking, genetic factors and other prevalent diseases only partly explain IPF, and so this review aims to summarize recent progress in establishing which occupational exposures are important in cause.

RECENT FINDINGS: IPF is a rare disease, although it is the commonest idiopathic interstitial pneumonia. Epidemiological study suggests that incidence of IPF is increasing, particularly in older men. There are significant associations with IPF and occupational exposures to organic dust, including livestock, birds and animal feed, metal dust, wood dust and silica/minerals. Estimates of effect vary between studies, and are influenced by the distribution of employment, study design and case definition. Inhalation of asbestos fibres is a known cause of usual interstitial pneumonia (as seen histologically in IPF), though there are significant linear relationships between asbestos consumption, and mortality from both IPF and mesothelioma, leading to the hypothesis that low-level asbestos exposure may cause IPF.

SUMMARY: Research must focus on exposure-response relationships between asbestos and other occupational inhaled hazards, and IPF. Funding bodies and policy makers should acknowledge the significant occupational burden on IPF.}, } @article {pmid36046389, year = {2020}, author = {Viscardi, G and Di Natale, D and Fasano, M and Brambilla, M and Lobefaro, R and De Toma, A and Galli, G}, title = {Circulating biomarkers in malignant pleural mesothelioma.}, journal = {Exploration of targeted anti-tumor therapy}, volume = {1}, number = {6}, pages = {434-451}, pmid = {36046389}, issn = {2692-3114}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive tumor strictly connected to asbestos exposure. Prognosis is dismal as diagnosis commonly occurs in advanced stage. Radiological screenings have not proven to be effective and also pathological diagnosis may be challenging. In the era of precision oncology, validation of robust non-invasive biomarkers for screening of asbestos-exposed individuals, assessment of prognosis and prediction of response to treatments remains an important unmet clinical need. This review provides an overview on current understanding and possible applications of liquid biopsy in MPM, mostly focused on the utility as diagnostic and prognostic test.}, } @article {pmid31887736, year = {2019}, author = {Totaro, M and Giorgi, S and Filippetti, E and Gallo, A and Frendo, L and Privitera, G and Baggiani, A}, title = {[Asbestos in drinking water and hazards to human health: a narrative synthesis].}, journal = {Igiene e sanita pubblica}, volume = {75}, number = {4}, pages = {303-312}, pmid = {31887736}, issn = {0019-1639}, mesh = {Asbestos/*adverse effects/toxicity ; Carcinogens ; Drinking Water/*analysis ; Environmental Exposure/*adverse effects ; Humans ; Lung Neoplasms/etiology/prevention & control ; Mesothelioma/etiology/prevention & control ; Water Pollutants, Chemical/*toxicity ; }, abstract = {The term asbestos refers to six unique fibrous minerals mostly used in the production of asbestos cement sheets and pipes. According to the World Health Organization and the International Agency for Research on Cancer (IARC), there exists at least "sufficient evidence" that all types of asbestos may cause cancer in humans (mesothelioma, lung cancer, laryngeal tumor and ovarian cancer). The only asbestos limit in drinking water is 7 million fiber/liter. This study is a narrative synthesis about the possible hazards to human health related to the presence of asbestos in drinking water. The various scientific studies and epidemiological reports examined highlight that there is an ongoing debate on the possible carcinogenic risk associated with asbestos exposure through ingestion. Nevertheless, considering the latency with which diseases caused by asbestos may emerge, control measures should be adopted.}, } @article {pmid31878930, year = {2019}, author = {Vimercati, L and Cavone, D and Delfino, MC and De Maria, L and Caputi, A and Ferri, GM and Serio, G}, title = {Response to the "Letter to the Editor" by Gabor Mezei et al., Comments on Vimercati et al., 2019, "Asbestos exposure and malignant mesothelioma of the tunica vaginalis testis: a systematic review and the experience of the Apulia (Southern Italy) mesothelioma register".}, journal = {Environmental health : a global access science source}, volume = {18}, number = {1}, pages = {112}, pmid = {31878930}, issn = {1476-069X}, } @article {pmid31878926, year = {2019}, author = {Mezei, G and Chang, ET and Mowat, FS and Moolgavkar, SH}, title = {Comments on Vimercati et al., 2019, "Asbestos exposure and malignant mesothelioma of the tunica vaginalis testis: a systematic review and the experience of the Apulia (southern Italy) mesothelioma register".}, journal = {Environmental health : a global access science source}, volume = {18}, number = {1}, pages = {111}, pmid = {31878926}, issn = {1476-069X}, } @article {pmid31876833, year = {2020}, author = {Kodama, E and Kodama, T and Ichikawa, T and Ikoma, H and Hashimoto, J}, title = {18F-FDG Uptake of Localized Malignant Peritoneal Mesothelioma.}, journal = {Clinical nuclear medicine}, volume = {45}, number = {2}, pages = {161-163}, doi = {10.1097/RLU.0000000000002901}, pmid = {31876833}, issn = {1536-0229}, mesh = {Aged ; Fluorodeoxyglucose F18 ; Humans ; Lung Neoplasms/*diagnostic imaging ; Male ; Mesothelioma/*diagnostic imaging ; Mesothelioma, Malignant ; Peritoneal Neoplasms/*diagnostic imaging ; *Positron Emission Tomography Computed Tomography ; Radiopharmaceuticals ; }, abstract = {We present 2 cases of malignant peritoneal mesothelioma (MPM) characterized by a localized solid mass without ascites and showing F-FDG uptake. A 79-year-old man with a history of asbestos exposure suffered from an epithelioid MPM originating from the hepatoduodenal ligament with FDG uptake (SUVmax 16.8). Another 80-year-old man with esophageal cancer showed desmoplastic MPM of the small bowel mesentery with FDG uptake (SUVmax 4.0). Desmoplastic MPM is more aggressive and yields poorer prognosis compared with the epithelioid type. However, the present desmoplastic MPM case showed mild FDG uptake because of rich fibrosis.}, } @article {pmid31876584, year = {2020}, author = {Pavlisko, EN and Liu, B and Green, C and Sporn, TA and Roggli, VL}, title = {Malignant Diffuse Mesothelioma in Women: A Study of 354 Cases.}, journal = {The American journal of surgical pathology}, volume = {44}, number = {3}, pages = {293-304}, doi = {10.1097/PAS.0000000000001418}, pmid = {31876584}, issn = {1532-0979}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/toxicity ; Carcinogens/toxicity ; Databases, Factual ; Environmental Exposure/adverse effects ; Female ; Humans ; Lung Neoplasms/chemically induced/diagnosis/mortality/*pathology ; Mesothelioma/chemically induced/diagnosis/mortality/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Prognosis ; Survival Analysis ; United States/epidemiology ; }, abstract = {We reviewed 354 cases of malignant diffuse mesothelioma (MM) in women from a database of 2858 histologically confirmed MM cases. There was a pleural predominance with 78% pleural MM and 22% peritoneal MM. The pleural tumors consisted of 72% epithelioid, 19% biphasic, and 9% sarcomatoid variant. The peritoneal tumors consisted of 82% epithelioid, 13% biphasic, and 5% sarcomatoid. The immunohistochemical profile was typical of what is well-accepted and previously described for MM. When examining tumor subtype and location, there was a trend toward epithelioid subtype and peritoneal location; however, this did not reach statistical significance. Age at the time of diagnosis ranged from 19 to 93 years with a mean of 60 years. The median age at time of diagnosis for pleural MM was 65 years and for peritoneal MM was 52 years. A further look at age and histologic subtype showed no statistically significant difference in age between MM subtypes. Survival was greatest for epithelioid variant, and this was magnified in the peritoneum. A majority of our cases were exposed to asbestos through a household contact. Asbestosis and parietal pleural plaque were present in 5% and 50% of cases with data, respectively. Fiber analysis data was available in 67 cases; 38 cases had elevated asbestos fiber burden, and tremolite was the most common asbestos fiber type detected. Commercial and noncommercial amphibole asbestos fibers were elevated in nearly equal numbers of cases.}, } @article {pmid31868762, year = {2020}, author = {Steffen, JE and Tran, T and Yimam, M and Clancy, KM and Bird, TB and Rigler, M and Longo, W and Egilman, DS}, title = {Serous Ovarian Cancer Caused by Exposure to Asbestos and Fibrous Talc in Cosmetic Talc Powders-A Case Series.}, journal = {Journal of occupational and environmental medicine}, volume = {62}, number = {2}, pages = {e65-e77}, doi = {10.1097/JOM.0000000000001800}, pmid = {31868762}, issn = {1536-5948}, mesh = {*Asbestos ; Asbestos, Amphibole ; *Cosmetics ; Environmental Exposure/*analysis ; Female ; Humans ; Mesothelioma ; Middle Aged ; Ovarian Neoplasms/*chemically induced ; Powders ; *Talc ; }, abstract = {OBJECTIVE: Asbestos is a known cause of ovarian cancer. We report 10 cases of serous ovarian cancer among users of Johnson & Johnson (J&J) asbestos-containing "cosmetic" talc products.

METHODS: We conducted an asbestos exposure assessment during talc application and analyzed surgical tissues and talc containers for asbestos and talc.

RESULTS: Talc was found in all cases and tremolite and/or anthophyllite asbestos was found in 8/10 cases. The asbestos fibers found in the "cosmetic" talc containers matched those found in tissues. We estimated inhaled asbestos dose ranged from 0.38 to 5.18 fiber years.

CONCLUSION: We provide evidence that the inhaled dose of asbestos/fibrous talc from "cosmetic" talc use causes ovarian cancer. The unique combination of the types of asbestiform minerals detected in cancerous tissue and "cosmetic" talc is a fingerprint for exposure to asbestos-containing talc.}, } @article {pmid31867277, year = {2019}, author = {Chu, GJ and van Zandwijk, N and Rasko, JEJ}, title = {The Immune Microenvironment in Mesothelioma: Mechanisms of Resistance to Immunotherapy.}, journal = {Frontiers in oncology}, volume = {9}, number = {}, pages = {1366}, pmid = {31867277}, issn = {2234-943X}, abstract = {Although mesothelioma is the consequence of a protracted immune response to asbestos fibers and characterized by a clear immune infiltrate, novel immunotherapy approaches show less convincing results as compared to those seen in melanoma and non-small cell lung cancer. The immune suppressive microenvironment in mesothelioma is likely contributing to this therapy resistance. Therefore, it is important to explore the characteristics of the tumor microenvironment for explanations for this recalcitrant behavior. This review describes the stromal, cytokine, metabolic, and cellular milieu of mesothelioma, and attempts to make connection with the outcome of immunotherapy trials.}, } @article {pmid35582270, year = {2019}, author = {Williams, M and Cheng, YY and Phimmachanh, M and Winata, P and van Zandwijk, N and Reid, G}, title = {Tumour suppressor microRNAs contribute to drug resistance in malignant pleural mesothelioma by targeting anti-apoptotic pathways.}, journal = {Cancer drug resistance (Alhambra, Calif.)}, volume = {2}, number = {4}, pages = {1193-1206}, pmid = {35582270}, issn = {2578-532X}, abstract = {Aim: Aberrant microRNA expression is a common event in cancer drug resistance, however its involvement in malignant pleural mesothelioma (MPM) drug resistance is largely unexplored. We aimed to investigate the contribution of microRNAs to the resistance to drugs commonly used in the treatment of MPM. Methods: Drug resistant MPM cell lines were generated by treatment with cisplatin, gemcitabine or vinorelbine. Expression of microRNAs was quantified using RT-qPCR. Apoptosis and drug sensitivity assays were carried out following transfection with microRNA mimics or BCL2 siRNAs combined with drugs. Results: Expression of miR-15a, miR-16 and miR-34a was downregulated in MPM cells with acquired drug resistance. Transfection with miR-15a or miR-16 mimics reversed the resistance to cisplatin, gemcitabine or vinorelbine, whereas miR-34a reversed cisplatin and vinorelbine resistance only. Similarly, in parental cell lines, miR-15a or miR-16 mimics sensitised cells to all drugs, whereas miR-34a increased response to cisplatin and vinorelbine. Increased microRNA expression increased drug-induced apoptosis and caused BCL2 mRNA and protein reduction. RNAi-mediated knockdown of BCL2 partly recapitulated the increase in drug sensitivity in cisplatin and vinorelbine treated cells. Conclusion: Drug-resistant MPM cell lines exhibited reduced expression of tumour suppressor microRNAs. Increasing tumour suppressor of microRNA expression sensitised both drug resistant and parental cell lines to chemotherapeutic agents, in part through targeting of BCL2. Taken together, these data suggest that miR-15a, miR-16 and miR-34a are involved in the acquired and intrinsic drug resistance phenotype of MPM cells.}, } @article {pmid31850200, year = {2019}, author = {Tomasetti, M and Gaetani, S and Monaco, F and Neuzil, J and Santarelli, L}, title = {Epigenetic Regulation of miRNA Expression in Malignant Mesothelioma: miRNAs as Biomarkers of Early Diagnosis and Therapy.}, journal = {Frontiers in oncology}, volume = {9}, number = {}, pages = {1293}, pmid = {31850200}, issn = {2234-943X}, abstract = {Asbestos exposure leads to epigenetic and epigenomic modifications that, in association with ROS-induced DNA damage, contribute to cancer onset. Few miRNAs epigenetically regulated in MM have been described in literature; miR-126, however, is one of them, and its expression is regulated by epigenetic mechanisms. Asbestos exposure induces early changes in the miRNAs, which are reversibly expressed as protective species, and their inability to reverse reflects the inability of the cells to restore the physiological miRNA levels despite the cessation of carcinogen exposure. Changes in miRNA expression, which results from genetic/epigenetic changes during tumor formation and evolution, can be detected in fluids and used as cancer biomarkers. This article has reviewed the epigenetic mechanisms involved in miRNA expression in MM, focusing on their role as biomarkers of early diagnosis and therapeutic effects.}, } @article {pmid31846450, year = {2019}, author = {Apostoli, P and Boffetta, P and Bovenzi, M and Cocco, PL and Consonni, D and Cristaudo, A and Discalzi, G and Farioli, A and Manno, M and Mattioli, S and Pira, E and Soleo, L and Taino, G and Violante, FS and Zocchetti, C}, title = {Position Paper on Asbestos of the Italian Society of Occupational Medicine.}, journal = {La Medicina del lavoro}, volume = {110}, number = {6}, pages = {459-485}, pmid = {31846450}, issn = {0025-7818}, mesh = {*Asbestos ; *Asbestosis ; Humans ; Italy ; *Lung Neoplasms ; *Mesothelioma ; *Occupational Exposure ; *Occupational Medicine ; *Pleural Neoplasms ; Retrospective Studies ; }, abstract = {The Position Paper (PP) on asbestos of the Italian Society of Occupational Medicine (SIML) aims at providing a tool to the occupational physician to address current diagnostic criteria and results of epidemiological studies, and their consequences in terms of preventive and evaluation actions for insurance, compensation and litigation. The PP was based on an extensive review of the scientific literature and was compiled by a Working Group comprising researchers who have contributed to the international literature on asbestos-related diseases, as well as occupational physicians with extensive experience in the evaluation of risks and the medical surveillance of workers currently and formerly exposed to asbestos. The PP was drafted and reviewed between 2017 and 2018; its final version was prepared according to the guidelines of AGREE Reporting Checklist. All the members of the Working Group subscribed to the document, which was eventually approved by SIML's Executive Committee. The first section addresses industrial hygiene issues, such as methods for environmental monitoring, advantages and limitations of different microscopy techniques, the potential role of microfibers and approaches for retrospective assessment of exposure, in particular in epidemiological studies. The second section reviews the biological effects of asbestos with particular attention to the diagnostic aspects of asbestosis, pleural changes, mesothelioma and lung cancer. In the following section the criteria of causal attribution are discussed, together with different hypotheses on the form of the risk functions, with a comparison of the opinions prevalent in the literature. In particular, the models of the risk function for mesothelioma were examined, in the light of the hypothesis of an acceleration or anticipation of the events in relation to the dose. The last section discusses topics of immediate relevance for the occupational physician, such as health surveillance of former exposed and of workers currently exposed in remediation activities.}, } @article {pmid31842309, year = {2019}, author = {Vernez, D and Duperrex, O and Herrera, H and Perret, V and Rossi, I and Regamey, F and Guillemin, M}, title = {Exposure to Amosite-Containing Ceiling Boards in a Public School in Switzerland: A Case Study.}, journal = {International journal of environmental research and public health}, volume = {16}, number = {24}, pages = {}, pmid = {31842309}, issn = {1660-4601}, mesh = {Adolescent ; Air Pollutants/*analysis ; Air Pollution, Indoor/*analysis ; Asbestos, Amosite/*analysis ; Child ; *Construction Materials ; Dose-Response Relationship, Drug ; Environmental Monitoring ; Female ; Humans ; *Lung Neoplasms ; Male ; *Mesothelioma ; Mesothelioma, Malignant ; Risk Assessment ; Schools ; Switzerland ; }, abstract = {The measurement of an airborne concentration in Amosite fibers above 5035 F/m[3] in a school prompted a retrospective quantitative health risk assessment. Dose estimates were built using air measurements, laboratory experiments, previous exposure data, and interviews. A dose response model was adapted for amosite-only exposure and adjusted for the life expectancy and lung cancer incidence in the Swiss population. The average yearly concentrations found were 52-320 F/m[3]. The high concentration previously observed was not representative of the average exposure in the building. Overall, the risk estimates for the different populations of the school were low and in the range of 2 × 10[-6] to 3 × 10[-5] for mesothelioma and 4 × 10[-7] to 8 × 10[-6] for lung cancer. The results evidenced however that children have to be considered at higher risk when exposed to asbestos, and that the current reference method and target values are of limited use for amphibole-only exposures. This study confirmed that quantitative health risk assessments and participatory approaches are powerful tools to support public decisions and build constructive communication between exposed people, experts, and policy-makers.}, } @article {pmid31833271, year = {2019}, author = {Pellegrini, I and Sibille, A and Paulus, A and Vaillant, F and Radermecker, MA and Corhay, JL and Louis, R and Duysinx, B}, title = {[How I manage... Malignant pleural mesothelioma in 2019].}, journal = {Revue medicale de Liege}, volume = {74}, number = {12}, pages = {627-632}, pmid = {31833271}, issn = {0370-629X}, mesh = {Antineoplastic Combined Chemotherapy Protocols ; Bevacizumab ; Combined Modality Therapy ; Humans ; *Mesothelioma/drug therapy ; Pemetrexed ; *Pleural Neoplasms/drug therapy ; }, abstract = {Malignant pleural mesothelioma is a rare disease originating from mesothelial cells of the pleura and is related to asbestos exposure. The tumor is generally extended at the time of diagnosis and the treatment consists of a systemic palliative therapy. Radical approach is limited to very selected patients and is performed in expert centers but without validated schema. Radiotherapy alone is mainly used in palliative intent. Platinum-based chemotherapy in association with pemetrexed is the frontline standard of care and provides a 12-month overall survival. The addition of bevacizumab, an antiangiogenic drug, shows an improvement in median survival. To date, there is no second-line treatment approved for this disease and therefore inclusion in trials is recommended. Currently, various studies are investigating target therapy, immunotherapy and intrapleural perioperative treatment.}, } @article {pmid31823764, year = {2019}, author = {Kishimoto, T and Fujimoto, N and Ebara, T and Omori, T and Oguri, T and Niimi, A and Yokoyama, T and Kato, M and Usami, I and Nishio, M and Yoshikawa, K and Tokuyama, T and Tamura, M and Yokoyama, Y and Tsuboi, K and Matsuo, Y and Xu, J and Takahashi, S and Abdelgied, M and Alexander, WT and Alexander, DB and Tsuda, H}, title = {Serum levels of the chemokine CCL2 are elevated in malignant pleural mesothelioma patients.}, journal = {BMC cancer}, volume = {19}, number = {1}, pages = {1204}, pmid = {31823764}, issn = {1471-2407}, support = {14030101-01//Ministry of Health, Labour and Welfare/ ; 13801370//Ministry of Health, Labour and Welfare/ ; 16768893//Ministry of Health, Labour and Welfare/ ; H24//Princess Takamatsu Cancer Research Fund/ ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestosis/blood ; Biomarkers, Tumor/blood ; Chemokine CCL2/*blood ; Disease Progression ; Female ; Healthy Volunteers ; Humans ; Lung Neoplasms/*blood/pathology ; Male ; Mesothelioma/*blood/pathology ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/*blood ; Young Adult ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a debilitating disease of the pleural cavity. It is primarily associated with previous inhalation of asbestos fibers. These fibers initiate an oxidant coupled inflammatory response. Repeated exposure to asbestos fibers results in a prolonged inflammatory response and cycles of tissue damage and repair. The inflammation-associated cycles of tissue damage and repair are intimately involved in the development of asbestos-associated cancers. Macrophages are a key component of asbestos-associated inflammation and play essential roles in the etiology of a variety of cancers. Macrophages are also a source of C-C motif chemokine ligand 2 (CCL2), and a variety of tumor-types express CCL2. High levels of CCL2 are present in the pleural effusions of mesothelioma patients, however, CCL2 has not been examined in the serum of mesothelioma patients.

METHODS: The present study was carried out with 50 MPM patients and 356 subjects who were possibly exposed to asbestos but did not have disease symptoms and 41 healthy volunteers without a history of exposure to asbestos. The levels of CCL2 in the serum of the study participants was determined using ELISA.

RESULTS: Levels of CCL2 were significantly elevated in the serum of patients with advanced MPM.

CONCLUSIONS: Our findings are consistent with the premise that the CCL2/CCR2 axis and myeloid-derived cells play an important role in MPM and disease progression. Therapies are being developed that target CCL2/CCR2 and tumor resident myeloid cells, and clinical trials are being pursued that use these therapies as part of the treatment regimen. The results of trials with patients with a similar serum CCL2 pattern as MPM patients will have important implications for the treatment of MPM.}, } @article {pmid31821579, year = {2020}, author = {Ferrante, D and Mirabelli, D and Silvestri, S and Azzolina, D and Giovannini, A and Tribaudino, P and Magnani, C}, title = {Mortality and mesothelioma incidence among chrysotile asbestos miners in Balangero, Italy: A cohort study.}, journal = {American journal of industrial medicine}, volume = {63}, number = {2}, pages = {135-145}, doi = {10.1002/ajim.23071}, pmid = {31821579}, issn = {1097-0274}, support = {//This study was partially supported by Istituto Superiore di Sanità - Progetto Amianto (to C.M)/International ; }, mesh = {Adult ; Asbestos, Serpentine/*toxicity ; Asbestosis/*mortality ; Cause of Death ; Humans ; Incidence ; Italy/epidemiology ; Lung Neoplasms/*mortality ; Male ; Mesothelioma, Malignant/*mortality ; Middle Aged ; Mining ; Occupational Diseases/*mortality ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*mortality ; Risk Factors ; }, abstract = {BACKGROUND: We studied cancer mortality and mesothelioma incidence in 974 male workers employed at least 6 months at the Balangero mine (Italy), the largest chrysotile mine in Western Europe, active from 1917 to 1985.

METHODS: Vital status as of 31 May 2013, causes of deaths and mesothelioma incidence from 1990 were ascertained. Past exposure to asbestos by working area and calendar period was estimated, based on historical data of fibers concentrations. Individual cumulative exposure was assessed by applying estimates to the job history of cohort members. Standardized mortality ratios (SMRs) for selected causes and standardized incidence ratios for malignant mesothelioma (MM) were calculated based on regional reference rates. Poisson regression analysis was used to study MM and lung cancer risk by latency, duration, and cumulative exposure.

RESULTS: Mortality was increased for all causes (SMR = 1.28; 95% confidence interval [CI] = 1.17-1.40), pleural cancer (SMR = 4.30; 95% CI = 1.58-9.37), asbestosis (SMR = 375.06; 95% CI = 262.68-519.23). An increase was also found for lung cancer (SMR = 1.14; 95% CI =  0.81-1.55) and peritoneal cancer (SMR = 3.25; 95% CI = 0.39-11.75). The risk of both pleural and peritoneal cancer mortality and of mesothelioma incidence increased with increasing cumulative exposure, duration, and latency. Poisson regression analyses showed an increase in mesothelioma risk with cumulative asbestos exposure and suggest a similar trend for lung cancer. Asbestosis mortality also increased with cumulative exposure.

CONCLUSIONS: Among Balangero chrysotile miners and millers, the occurrence of malignant and nonmalignant asbestos-related diseases was increased by exposure, with dose-response relation. The study confirms the carcinogenicity of chrysotile asbestos, in particular for pleural mesothelioma.}, } @article {pmid31819191, year = {2020}, author = {Urso, L and Cavallari, I and Sharova, E and Ciccarese, F and Pasello, G and Ciminale, V}, title = {Metabolic rewiring and redox alterations in malignant pleural mesothelioma.}, journal = {British journal of cancer}, volume = {122}, number = {1}, pages = {52-61}, pmid = {31819191}, issn = {1532-1827}, mesh = {Animals ; Antineoplastic Agents/therapeutic use ; Asbestos/adverse effects ; Cell Transformation, Neoplastic/metabolism ; Cisplatin/therapeutic use ; Humans ; Loss of Function Mutation ; Lung Neoplasms/drug therapy/etiology/*genetics/*metabolism ; Mesothelioma/drug therapy/etiology/*genetics/*metabolism ; Mesothelioma, Malignant ; Oxidation-Reduction ; Pleural Neoplasms/drug therapy/etiology/*genetics/*metabolism ; Reactive Oxygen Species/metabolism ; Transforming Growth Factor beta ; Transforming Growth Factor beta1/metabolism ; Tumor Suppressor Proteins/genetics ; Ubiquitin Thiolesterase/genetics ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare malignancy of mesothelial cells with increasing incidence, and in many cases, dismal prognosis due to its aggressiveness and lack of effective therapies. Environmental and occupational exposure to asbestos is considered the main aetiological factor for MPM. Inhaled asbestos fibres accumulate in the lungs and induce the generation of reactive oxygen species (ROS) due to the presence of iron associated with the fibrous silicates and to the activation of macrophages and inflammation. Chronic inflammation and a ROS-enriched microenvironment can foster the malignant transformation of mesothelial cells. In addition, MPM cells have a highly glycolytic metabolic profile and are positive in [18]F-FDG PET analysis. Loss-of-function mutations of BRCA-associated protein 1 (BAP1) are a major contributor to the metabolic rewiring of MPM cells. A subset of MPM tumours show loss of the methyladenosine phosphorylase (MTAP) locus, resulting in profound alterations in polyamine metabolism, ATP and methionine salvage pathways, as well as changes in epigenetic control of gene expression. This review provides an overview of the perturbations in metabolism and ROS homoeostasis of MPM cells and the role of these alterations in malignant transformation and tumour progression.}, } @article {pmid31814459, year = {2019}, author = {Pfau, JC and McNew, T and Hanley, K and Swan, L and Black, B}, title = {Autoimmune markers for progression of Libby amphibole lamellar pleural thickening.}, journal = {Inhalation toxicology}, volume = {31}, number = {11-12}, pages = {409-419}, pmid = {31814459}, issn = {1091-7691}, support = {UL1 TR002319/TR/NCATS NIH HHS/United States ; }, mesh = {Antibodies, Antinuclear/metabolism ; Asbestos, Amphibole/*toxicity ; Autoantibodies/*metabolism ; Biomarkers ; Cell Line ; Collagen ; Cytokines/genetics/metabolism ; Gene Expression Regulation/drug effects ; Humans ; Pleura/*drug effects/*pathology ; Sensitivity and Specificity ; }, abstract = {Exposure to Libby Asbestiform Amphibole (LAA) is associated with asbestos-related diseases, including mesothelioma, pulmonary carcinoma, pleural fibrosis, and systemic autoimmune diseases. The pleural fibrosis can manifest as a rapidly progressing lamellar pleural thickening (LPT), which causes thoracic pain, dyspnea, and worsening pulmonary function tests (PFT). It is refractory to treatment and frequently fatal.Objective: Because of the immune dysfunction that has been described in the LAA-exposed population and the association of pleural manifestations with the presence of autoantibodies, this study tested whether specific immunological factors were associated with progressive LPT and whether they could be used as markers of progressive disease.Methods: Subjects were placed into three study groups defined as (1) progressive LPT, (2) stable LPT, (3) no LPT. Serum samples were tested for antinuclear autoantibodies, mesothelial cell autoantibodies, anti-plasminogen antibodies, IL1 beta, and IL17; which have all been shown to be elevated in mice and/or humans exposed to LAA.Results: Group 1 had significantly higher mean values for all of the autoantibodies, but not IL1 or IL-17, compared to the control Group 3. All three autoantibody tests had high specificity but low sensitivity, but ROC area-under-the-curve values for all three antibodies were over 0.7, statistically higher than a test with no value. When all LPT subjects were combined (Progressive plus Stable), no marker had predictive value for disease.Conclusion: The data support the hypothesis that progressive LPT is associated with immunological findings that may serve as an initial screen for progressive LPT.}, } @article {pmid31812249, year = {2020}, author = {Consonni, D and De Matteis, S and Dallari, B and Pesatori, AC and Riboldi, L and Mensi, C}, title = {Impact of an asbestos cement factory on mesothelioma incidence in a community in Italy.}, journal = {Environmental research}, volume = {183}, number = {}, pages = {108968}, doi = {10.1016/j.envres.2019.108968}, pmid = {31812249}, issn = {1096-0953}, mesh = {Adult ; *Asbestos/toxicity ; Female ; Humans ; Incidence ; Italy/epidemiology ; Male ; *Mesothelioma/epidemiology ; *Occupational Exposure ; *Pleural Neoplasms/epidemiology ; }, abstract = {BACKGROUND: Broni is a small town (9000 inhabitants) in the province of Pavia, Lombardy, north-west Italy, where the second largest Italian asbestos cement factory (Fibronit) was in operation between 1932 and 1993. Based on Lombardy Mesothelioma Registry (RML) data (2000-2011), we previously showed a high impact of asbestos exposure on malignant mesothelioma (MM) incidence among Fibronit workers, their families, and people living in Broni and in the nearby town of Stradella (11,000 residents). Given the great concern of the community, we have recently updated the data regarding 5 more years (2012-2016).

METHODS: From the RML database we extracted subjects who ever worked in Fibronit, their family members, ever residents in Broni, and subjects living in Stradella and nearby towns at the time of diagnosis. For each type of exposure we calculated standardized incidence ratios (SIR = observed/expected cases).

RESULTS: In the period 2000-2016 we registered 56 cases (2.52 expected, SIR = 22.2), 49 men (41 pleural, 8 peritoneal MM), 7 women (5 pleural, 2 peritoneal MM) with past occupational exposure in Fibronit. Among subjects never occupationally exposed and never exposed to extra-occupational sources unrelated to Fibronit, we counted 39 cases (4.24 expected, SIR = 9.2), 10 men (all pleural MM), 29 women (28 pleural, 1 peritoneal MM) in Fibronit workers' families, 91 pleural mesothelioma cases (7.43 expected, SIR = 12.2, 31 men, 60 women), ever residents in Broni, and 25 pleural mesothelioma cases (3.05 expected, SIR = 8.2, 6 men, 19 women) living in Stradella at the time of diagnosis. The overall number of excess cases was about 194 (211 against 17.24 expected). In the remaining adjacent (No. 8) and surrounding (No. 17) municipalities (32,000 people) there were 7 cases (1 men, 6 women, 8.85 expected).

CONCLUSION: The mesothelioma burden related to the asbestos cement factory is still high on factory workers, their families, and residents in Broni and Stradella towns.}, } @article {pmid31812210, year = {2019}, author = {Sonnick, MA and Weisman, S and Borczuk, AC and Turetz, ML}, title = {A Man in His 20s With Cough, Unilateral Pleural Effusion, and Nodular Pleural Thickening.}, journal = {Chest}, volume = {156}, number = {6}, pages = {e121-e126}, doi = {10.1016/j.chest.2019.05.040}, pmid = {31812210}, issn = {1931-3543}, mesh = {Adenocarcinoma of Lung/diagnosis ; Adult ; Asbestos ; Bartonella Infections/diagnosis ; Biopsy ; Cough/etiology ; Diagnosis, Differential ; Dyspnea/etiology ; Environmental Exposure ; Humans ; Lung Neoplasms/complications/*diagnosis/pathology ; Lymph Nodes/diagnostic imaging ; Lymphoma, Non-Hodgkin/diagnosis ; Male ; Mesothelioma/complications/*diagnosis/pathology ; Mesothelioma, Malignant ; Palatine Tonsil/diagnostic imaging ; Pleural Effusion/diagnostic imaging/etiology ; Pleural Effusion, Malignant/*diagnostic imaging/etiology ; Pleural Neoplasms/complications/*diagnosis/pathology ; Positron-Emission Tomography ; Spleen/diagnostic imaging ; Sweating ; Talc ; Thoracic Surgery, Video-Assisted ; }, abstract = {A man in his 20s presented to the ED after several months of progressive dyspnea, dry cough, and night sweats. He had no chest pain, fevers, weight loss, or sick contacts. He was previously healthy and took no medications. Social history was notable for 5 pack-years of tobacco use. The patient was sexually active with male partners and had a recent partner infected with human T-lymphotropic virus. The patient worked in set design and window installations, and wore a respirator when working around solvents and resins. From ages 2 to 7 years, he frequently visited buildings at his parents' workplace that were undergoing asbestos abatement. From ages 7 to 24 years, he frequently visited pottery studios where talc-containing products were used. He frequently visited northern Massachusetts, and infections with Borrelia burgdorferi and Bartonella henselae were common in family members. His stepfather had recently been infected with Anaplasma. There was no family history of cancer.}, } @article {pmid31807495, year = {2019}, author = {Johnson, TG and Schelch, K and Mehta, S and Burgess, A and Reid, G}, title = {Corrigendum: Why Be One Protein When You Can Affect Many? The Multiple Roles of YB-1 in Lung Cancer and Mesothelioma.}, journal = {Frontiers in cell and developmental biology}, volume = {7}, number = {}, pages = {293}, pmid = {31807495}, issn = {2296-634X}, abstract = {[This corrects the article DOI: 10.3389/fcell.2019.00221.].}, } @article {pmid31783178, year = {2020}, author = {Mian, I and Abdullaev, Z and Morrow, B and Kaplan, RN and Gao, S and Miettinen, M and Schrump, DS and Zgonc, V and Wei, JS and Khan, J and Pack, S and Hassan, R}, title = {Anaplastic Lymphoma Kinase Gene Rearrangement in Children and Young Adults With Mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {15}, number = {3}, pages = {457-461}, pmid = {31783178}, issn = {1556-1380}, support = {Z01 BC010816/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Anaplastic Lymphoma Kinase/genetics ; Child ; Female ; Gene Rearrangement ; Humans ; In Situ Hybridization, Fluorescence ; *Lung Neoplasms/genetics ; Male ; *Mesothelioma/genetics ; Prospective Studies ; Receptor Protein-Tyrosine Kinases/genetics ; Young Adult ; }, abstract = {INTRODUCTION: Children and young adults diagnosed with malignant mesothelioma may have unique genetic characteristics. In this study, we evaluated for the presence of the anaplastic lymphoma kinase (ALK) translocations in these patients.

METHODS: In a prospective study of mesothelioma natural history (ClinicalTrials.gov number NCT01950572), we assessed for the presence of the ALK translocation in patients younger than 40 years, irrespective of the site of disease. The presence of this translocation was assessed by means of fluorescence in situ hybridization (FISH). If the patients tested positive for the ALK translocation, both immunohistochemistry and RNA sequencing were performed on the tumor specimen.

RESULTS: Between September 2013 and December 2018, 373 patients were enrolled in the mesothelioma natural history study, of which 32 patients were 40 years old or younger at the time of their mesothelioma diagnosis. There were 25 patients with peritoneal mesothelioma, five with pleural mesothelioma, one with pericardial mesothelioma, and one with bicompartmental mesothelioma. Presence of an ALK translocation by FISH was seen in two of the 32 patients (6%) with mesothelioma. Both patients, a 14-year-old female and a 27-year-old male, had peritoneal mesothelioma and had no history of asbestos exposure, prior radiation therapy, or predisposing germline mutations. Neither had detectable ALK expression by immunohistochemistry. RNA sequencing revealed the presence of an STRN fusion partner in the female patient but failed to identify any fusion protein in the male patient.

CONCLUSIONS: Young patients with peritoneal mesothelioma should be evaluated for the presence of ALK translocations. Presence of this translocation should be assessed by FISH and these patients could potentially benefit from tyrosine kinase inhibitors targeting ALK.}, } @article {pmid31766522, year = {2019}, author = {Martinotti, S and Patrone, M and Moccia, F and Ranzato, E}, title = {Targeting Calcium Signalling in Malignant Mesothelioma.}, journal = {Cancers}, volume = {11}, number = {12}, pages = {}, pmid = {31766522}, issn = {2072-6694}, abstract = {Calcium ions (Ca[2+]) are central in cancer development and growth, serving as a major signaling system determining the cell's fate. Therefore, the investigation of the functional roles of ion channels in cancer development may identify novel approaches for determining tumor prognosis. Malignant mesothelioma is an aggressive cancer that develops from the serosal surface of the body, strictly related to asbestos exposure. The treatment of malignant mesothelioma is complex and the survival outcomes, rather than the overall survival data are, to date, disappointedly daunting. Nevertheless, conventional chemotherapy is almost ineffective. The alteration in the expression and/or activity of Ca[2+] permeable ion channels seems to be characteristic of mesothelioma cells. In this review, we explore the involvement of the Ca[2+]toolkit in this disease. Moreover, the established sensitivity of some Ca[2+]channels to selective pharmacological modulators makes them interesting targets for mesothelioma cancer therapy.}, } @article {pmid31755376, year = {2019}, author = {Celsi, F and Crovella, S and Moura, RR and Schneider, M and Vita, F and Finotto, L and Zabucchi, G and Zacchi, P and Borelli, V}, title = {Pleural mesothelioma and lung cancer: the role of asbestos exposure and genetic variants in selected iron metabolism and inflammation genes.}, journal = {Journal of toxicology and environmental health. Part A}, volume = {82}, number = {20}, pages = {1088-1102}, doi = {10.1080/15287394.2019.1694612}, pmid = {31755376}, issn = {1528-7394}, mesh = {Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Female ; Humans ; Inflammasomes/*genetics ; Iron/*metabolism ; Italy ; Lung Neoplasms/chemically induced/*epidemiology ; Male ; Mesothelioma/chemically induced/*epidemiology ; Mesothelioma, Malignant ; Pleural Neoplasms/chemically induced/*epidemiology ; Prevalence ; Retrospective Studies ; Risk Factors ; }, abstract = {Two of the major cancerous diseases associated with asbestos exposure are malignant pleural mesothelioma (MPM) and lung cancer (LC). In addition to asbestos exposure, genetic factors have been suggested to be associated with asbestos-related carcinogenesis and lung genotoxicity. While genetic factors involved in the susceptibility to MPM were reported, to date the influence of individual genetic variations on asbestos-related lung cancer risk is still poorly understood. Since inflammation and disruption of iron (Fe) homeostasis are hallmarks of asbestos exposure affecting the pulmonary tissue, this study aimed at investigating the association between Fe-metabolism and inflammasome gene variants and susceptibility to develop LC or MPM, by comparing an asbestos-exposed population affected by LC with an "asbestos-resistant exposed population". A retrospective approach similar to our previous autopsy-based pilot study was employed in a novel cohort of autoptic samples, thus giving us the possibility to corroborate previous findings obtained on MPM by repeating the analysis in a novel cohort of autoptic samples. The protective role of HEPH coding SNP was further confirmed. In addition, the two non-coding SNPs, either in FTH1 or in TF, emerged to exert a similar protective role in a new cohort of LC exposed individuals from the same geographic area of MPM subjects. No association was found between NLRP1 and NLRP3 polymorphisms with susceptibility to develop MPM and LC. Further research into a specific MPM and LC "genetic signature" may be needed to broaden our knowledge of the genetic landscape attributed to result in MPM and LC.}, } @article {pmid31743489, year = {2020}, author = {Cummings, KJ and Becich, MJ and Blackley, DJ and Deapen, D and Harrison, R and Hassan, R and Henley, SJ and Hesdorffer, M and Horton, DK and Mazurek, JM and Pass, HI and Taioli, E and Wu, XC and Zauderer, MG and Weissman, DN}, title = {Workshop summary: Potential usefulness and feasibility of a US National Mesothelioma Registry.}, journal = {American journal of industrial medicine}, volume = {63}, number = {2}, pages = {105-114}, pmid = {31743489}, issn = {1097-0274}, support = {U19 OH009077/OH/NIOSH CDC HHS/United States ; R13 OH009753/OH/NIOSH CDC HHS/United States ; U54 GM104942/GM/NIGMS NIH HHS/United States ; R25 OH008802/OH/NIOSH CDC HHS/United States ; }, mesh = {Feasibility Studies ; Humans ; Mesothelioma, Malignant/*epidemiology ; Occupational Diseases/*epidemiology ; Population Surveillance ; Prognosis ; *Registries ; United States/epidemiology ; }, abstract = {The burden and prognosis of malignant mesothelioma in the United States have remained largely unchanged for decades, with approximately 3200 new cases and 2400 deaths reported annually. To address care and research gaps contributing to poor outcomes, in March of 2019 the Mesothelioma Applied Research Foundation convened a workshop on the potential usefulness and feasibility of a national mesothelioma registry. The workshop included formal presentations by subject matter experts and a moderated group discussion. Workshop participants identified top priorities for a registry to be (a) connecting patients with high-quality care and clinical trials soon after diagnosis, and (b) making useful data and biospecimens available to researchers in a timely manner. Existing databases that capture mesothelioma cases are limited by factors such as delays in reporting, deidentification, and lack of exposure information critical to understanding as yet unrecognized causes of disease. National disease registries for amyotrophic lateral sclerosis (ALS) in the United States and for mesothelioma in other countries, provide examples of how a registry could be structured to meet the needs of patients and the scientific community. Small-scale pilot initiatives should be undertaken to validate methods for rapid case identification, develop procedures to facilitate patient access to guidelines-based standard care and investigational therapies, and explore approaches to data sharing with researchers. Ultimately, federal coordination and funding will be critical to the success of a National Mesothelioma Registry in improving mesothelioma outcomes and preventing future cases of this devastating disease.}, } @article {pmid31732616, year = {2020}, author = {Kandasamy, S and Adhikary, G and Rorke, EA and Friedberg, JS and Mickle, MB and Alexander, HR and Eckert, RL}, title = {The YAP1 Signaling Inhibitors, Verteporfin and CA3, Suppress the Mesothelioma Cancer Stem Cell Phenotype.}, journal = {Molecular cancer research : MCR}, volume = {18}, number = {3}, pages = {343-351}, pmid = {31732616}, issn = {1557-3125}, support = {R01 CA184027/CA/NCI NIH HHS/United States ; R01 CA211909/CA/NCI NIH HHS/United States ; R25 GM055036/GM/NIGMS NIH HHS/United States ; T32 CA154274/CA/NCI NIH HHS/United States ; }, mesh = {Adaptor Proteins, Signal Transducing/*antagonists & inhibitors ; Animals ; Humans ; Mesothelioma/*drug therapy ; Mice ; Neoplastic Stem Cells/*drug effects ; Phenotype ; Photosensitizing Agents/pharmacology/*therapeutic use ; Signal Transduction ; Transcription Factors/*antagonists & inhibitors ; Transfection ; Verteporfin/pharmacology/*therapeutic use ; YAP-Signaling Proteins ; }, abstract = {Mesothelioma is an aggressive cancer that has a poor prognosis. Tumors develop in the mesothelial lining of the pleural and peritoneal cavities in response to asbestos exposure. Surgical debulking followed by chemotherapy is initially effective, but this treatment ultimately selects for resistant cells that form aggressive and therapy-resistant recurrent tumors. Mesothelioma cancer stem cells (MCS) are a highly aggressive subpopulation present in these tumors that are responsible for tumor maintenance and drug resistance. In this article, we examine the impact of targeting YAP1/TAZ/TEAD signaling in MCS cells. YAP1, TAZ, and TEADs are transcriptional mediators of the Hippo signaling cascade that activate gene expression to drive tumor formation. We show that two YAP1 signaling inhibitors, verteporfin and CA3, attenuate the MCS cell phenotype. Verteporfin or CA3 treatment reduces YAP1/TEAD level/activity to suppress MCS cell spheroid formation, Matrigel invasion, migration, and tumor formation. These agents also increase MCS cell apoptosis. Moreover, constitutively active YAP1 expression antagonizes inhibitor action, suggesting that loss of YAP1/TAZ/TEAD signaling is required for response to verteporfin and CA3. These agents are active against mesothelioma cells derived from peritoneal (epithelioid) and patient-derived pleural (sarcomatoid) mesothelioma, suggesting that targeting YAP1/TEAD signaling may be a useful treatment strategy. IMPLICATIONS: These studies suggest that inhibition of YAP1 signaling may be a viable approach to treating mesothelioma.}, } @article {pmid31727556, year = {2019}, author = {Lorentz, E and Despreaux, T and Quignette, A and Chinet, T and Descatha, A}, title = {[Screening of occupational exposure to asbestos and silica by job-exposure matrix among patients with lung cancer and mesothelioma].}, journal = {Revue des maladies respiratoires}, volume = {36}, number = {10}, pages = {1088-1095}, doi = {10.1016/j.rmr.2019.08.006}, pmid = {31727556}, issn = {1776-2588}, mesh = {Adult ; Aged ; Aged, 80 and over ; Algorithms ; Asbestos/toxicity ; Asbestosis/complications/*diagnosis/epidemiology ; Carcinoma, Bronchogenic/diagnosis/*epidemiology/etiology ; Female ; France/epidemiology ; Humans ; Lung Neoplasms/diagnosis/*epidemiology/etiology ; Male ; Mass Screening/*methods ; Mesothelioma/diagnosis/*epidemiology/etiology ; Middle Aged ; Occupational Diseases/diagnosis ; Occupational Exposure/analysis ; Silicon Dioxide/toxicity ; Silicosis/complications/*diagnosis/epidemiology ; Surveys and Questionnaires ; Work/statistics & numerical data ; }, abstract = {INTRODUCTION: In the context of underreporting of occupational diseases, the aim was to study the validity of silica and asbestos job-exposure matrices in screening occupational exposure in the field of thoracic oncology.

METHODS: Fifty patients hospitalized with primitive lung cancer or mesothelioma in a university hospital center in the Hauts-de-Seine department of France were included between November 2016 and September 2017. For each patient 1/the job history was collected, from which data was entered single-blindly into the job-exposure matrices by a resident in occupational medicine, 2/a questionnaire (Q-SPLF) was completed similarly, and 3/the patients also had a consultation with a chief resident in occupational medicine, considered the gold standard. The main outcome was the diagnostic performance of the matrices. The Q-SPLF diagnostic performance was also studied.

RESULTS: The asbestos and silica matrices had sensitivities of 100%, specificities of respectively 76.1% and 87.8%, the positive likelihood ratios were at 4.19 [2.5-6] and 8.17 [3.8-10], and the negative likelihood ratios were at 0. The Q-SPLF diagnostic performance was comparable to that of the matrices.

CONCLUSIONS: The matrices and the questionnaire have a great diagnostic performance which seems interesting for a use as a screening tool for occupational exposures. These results have yet to be confirmed by large-scale studies.}, } @article {pmid31714372, year = {2020}, author = {Larson, TC and Williamson, L and Antao, VC}, title = {Follow-Up of the Libby, Montana Screening Cohort: A 17-Year Mortality Study.}, journal = {Journal of occupational and environmental medicine}, volume = {62}, number = {1}, pages = {e1-e6}, pmid = {31714372}, issn = {1536-5948}, support = {CC999999/ImCDC/Intramural CDC HHS/United States ; }, mesh = {Adult ; Aluminum Silicates ; Asbestos ; Asbestos, Amphibole ; Asbestosis/*epidemiology ; Biometry ; Cohort Studies ; Environmental Exposure/*statistics & numerical data ; Female ; Follow-Up Studies ; Humans ; Lung ; Lung Neoplasms ; Male ; Mesothelioma/epidemiology ; Middle Aged ; Montana/epidemiology ; Occupational Exposure/*statistics & numerical data ; }, abstract = {OBJECTIVE: To evaluate mortality patterns among participants in a community-based screening program for asbestos-related disease.

METHODS: We calculated standardized mortality ratios (SMRs) and stratified results by exposure group (three occupational exposure groups, household contacts and residents without occupational asbestos exposure) and by radiographic abnormality presence.

RESULTS: All-cause mortality (15.8%; 1,429/8,043) was statistically lower than expected. Asbestosis was statistically elevated in all exposure groups. Lung cancer was moderately associated with vermiculite miner/miller employment. Mesothelioma was elevated in that same exposure group and among residents. Systemic autoimmune disease mortality was also elevated. Radiographic parenchymal abnormalities were associated with lung cancer mortality.

CONCLUSION: In addition to asbestos-related mortality in occupational exposure groups, this initial follow-up of this cohort also shows elevated mortality for some asbestos-related causes in non-occupational exposure groups.}, } @article {pmid31713586, year = {2020}, author = {Finkelstein, MM and Meisenkothen, C}, title = {Malignant Mesothelioma Among Employees of a Connecticut Factory That Manufactured Friction Materials Using Chrysotile Asbestos: An Update.}, journal = {Annals of work exposures and health}, volume = {64}, number = {1}, pages = {106-109}, doi = {10.1093/annweh/wxz082}, pmid = {31713586}, issn = {2398-7316}, mesh = {Aged ; Asbestos, Serpentine/*toxicity ; Connecticut ; Friction ; Humans ; *Lung Neoplasms/chemically induced ; Male ; Mesothelioma, Malignant/*chemically induced ; *Occupational Exposure/adverse effects ; }, abstract = {There is an ongoing argument about the potency of chrysotile asbestos to cause malignant mesothelioma. Authors of chrysotile risk assessments have relied upon the results of an epidemiologic study, published in 1984, to state that there were no mesotheliomas found among workers at a Connecticut friction products plant. McDonald reported the first two cases in 1986. In 2010, we reported the work histories and pathologic reports of five individuals from the Connecticut plant who were diagnosed with mesothelioma. Despite this, a review of the health effects of chrysotile published in 2018 continued to state that there were no cases of mesothelioma from this plant. We report here two new cases that were diagnosed after the publication of our previous report, bringing the current total to nine cases. We also discuss the results of previously unpublished air sampling data from the plant. Chrysotile, mainly from Canada, was the only asbestos fiber type used until 1957 when some anthophyllite was added in making paper discs and bands. Beyond this original description of the anthophyllite usage from McDonald, there is a dearth of information about the amount of anthophyllite used in the plant, the frequency of its use, and the specific departments where it was used. For over 30 years in the published literature, this factory has alternatively been described as a 'chrysotile' or 'predominantly chrysotile' factory. While it is clear that some anthophyllite was used in the factory (in addition to 400 pounds of crocidolite in the laboratory), given the volume, frequency, and processes using chrysotile, it still seems satisfactory to describe this cohort as a predominantly, but not exclusively, chrysotile-exposed cohort.}, } @article {pmid31701555, year = {2020}, author = {van Gerwen, M and Alpert, N and Flores, R and Taioli, E}, title = {An overview of existing mesothelioma registries worldwide, and the need for a US Registry.}, journal = {American journal of industrial medicine}, volume = {63}, number = {2}, pages = {115-120}, doi = {10.1002/ajim.23069}, pmid = {31701555}, issn = {1097-0274}, mesh = {Global Health ; Humans ; Mesothelioma, Malignant/*epidemiology ; Occupational Diseases/*epidemiology ; Population Surveillance ; *Registries ; United States/epidemiology ; }, abstract = {The association between asbestos exposure, mainly in occupational settings, and malignant mesothelioma has been well established; this has prompted several countries to establish mesothelioma epidemiologic surveillance programs often at the request of national agencies. This review compares currently existing mesothelioma registries worldwide to develop a concept model for a US real-time case capture mesothelioma registry. Five countries were identified with a mesothelioma specific registry, including Italy, France, UK, Australia, and South Korea. All, except the UK, used interviews to collect exposure data. Linkage with the national death index was available or was in future plans for all registries. The registries have limited information on treatment, quality of life, and other patient-centered outcomes such as symptoms and pain management. To thoroughly collect exposure data, "real-time" enrollment is preferable; to maximize the capture of mesothelioma cases, optimal coverage, and a simplified consent process are needed.}, } @article {pmid31693951, year = {2020}, author = {Gwenzi, W}, title = {Occurrence, behaviour, and human exposure pathways and health risks of toxic geogenic contaminants in serpentinitic ultramafic geological environments (SUGEs): A medical geology perspective.}, journal = {The Science of the total environment}, volume = {700}, number = {}, pages = {134622}, doi = {10.1016/j.scitotenv.2019.134622}, pmid = {31693951}, issn = {1879-1026}, mesh = {Africa ; Animals ; Asbestos, Serpentine ; Asbestosis ; Environmental Exposure ; *Environmental Monitoring ; Geology ; Hazardous Substances/*analysis ; Humans ; Iron ; Lung Neoplasms ; Mesothelioma ; Mesothelioma, Malignant ; Metals, Heavy ; Metals, Rare Earth ; Mining ; *Risk Assessment ; }, abstract = {Serpentinitic ultramafic geological environments (SUGEs) contain toxic geogenic contaminants (TGCs). Yet comprehensive reviews on the medical geology of SUGEs are still lacking. The current paper posits that TGCs occur widely in SUGEs, and pose human health risks. The objectives of the review are to: (1) highlight the nature, occurrence and behaviour of TGCs associated with SUGEs; (2) discuss the human intake pathways and health risks of TGCs; (4) identify the key risk factors predisposing human health to TGCs particularly in Africa; and (5) highlight key knowledge gaps and future research directions. TGCs of human health concern in SUGEs include chrysotile asbestos, toxic metals (Fe, Cr, Ni, Mn, Zn, Co), and rare earth elements. Human intake of TGCs occur via inhalation, and ingestion of contaminated drinking water, wild foods, medicinal plants, animal foods, and geophagic earths. Occupational exposure may occur in the mining, milling, sculpturing, engraving, and carving industries. African populations are particularly at high risk due to: (1) widespread consumption of wild foods, medicinal plants, untreated drinking water, and geophagic earths; (2) weak and poorly enforced environmental, occupational, and public health regulations; and (3) lack of human health surveillance systems. Human health risks of chrysotile include asbestosis, cancers, and mesothelioma. Toxic metals are redox active, thus generate reactive oxygen species causing oxidative stress. Dietary intake of iron and geophagy may increase the iron overload among native Africans who are genetically predisposed to such health risks. Synergistic interactions among TGCs particularly chrysotile and toxic metals may have adverse human health effects. The occurrence of SUGEs, coupled with the several risk factors in Africa, provides a unique and ideal setting for investigating the relationships between TGCs and human health risks. A conceptual framework for human health risk assessment and mitigation, and future research direction are highlighted.}, } @article {pmid31690138, year = {2019}, author = {Boyles, MSP and Poland, CA and Raftis, J and Duffin, R}, title = {Assessment of the physicochemical properties of chrysotile-containing brake debris pertaining to toxicity.}, journal = {Inhalation toxicology}, volume = {31}, number = {8}, pages = {325-342}, doi = {10.1080/08958378.2019.1683103}, pmid = {31690138}, issn = {1091-7691}, mesh = {Air Pollutants, Occupational/*chemistry ; Asbestos, Serpentine/*chemistry ; Automobiles ; Humans ; Macrophages/*drug effects ; Microscopy, Electron, Scanning ; Microscopy, Electron, Transmission ; Reactive Oxygen Species/analysis ; THP-1 Cells ; }, abstract = {Grinding and drilling of chrysotile asbestos-containing brake pads during the 20[th] century led to release of chrysotile, resulting in varying levels of workplace exposures of mechanics. Despite exposures, excess risk of mesothelioma remains in doubt. Objectives: The toxicity of particulates is primarily derived through a combination of physicochemical properties and dose and as such this study aimed to determine properties of asbestos-containing brake debris (BD) which may influence pathogenicity and potential of mesothelioma. Materials and Methods: Chrysotile-containing brake pads were ground - to reflect occupational activities, aerosolized, and size-fractionated to isolate respirable fractions. Analysis of morphology, biodurability, surface charge, and interactions with macrophages were undertaken. Results: The respirable fraction of BD contained ∼15-17% free chrysotile fibers thereby constituting a small but relevant potential long fiber dose. Acellular biodurability studies showed rapid dissolution and fragmentation of chrysotile fibers that was consistent for pure chrysotile control and BD samples. Conclusions: The long, free, respirable chrysotile fibers were present in BD, yet were of low bio-durability; incubation in artificial lysosomal fluid led to destruction of free fibers.}, } @article {pmid31684803, year = {2021}, author = {Waldron, T}, title = {ERA Merewether - And asbestos.}, journal = {Journal of medical biography}, volume = {29}, number = {4}, pages = {189-195}, doi = {10.1177/0967772019883550}, pmid = {31684803}, issn = {1758-1087}, mesh = {*Asbestos/toxicity ; Humans ; *Lung Neoplasms/chemically induced ; Male ; *Mesothelioma/chemically induced ; }, abstract = {After a succession of posts and studying for the Bar, Edward Merewether joined the Medical Inspectorate of Factories in 1927. Not long thereafter he was asked to undertake a study of the effects of asbestos exposure on the lungs. His results showed that asbestos workers had a significant risk of developing pulmonary fibrosis and this resulted in the promulgation of regulations to limit exposure. Some years later, Merewether showed that asbestos workers also had a higher than expected risk of developing lung cancer, but on this occasion there was no further protective legislation, and the association was not generally accepted until some years later. Merewether's name is inextricably linked with the risks of asbestos exposure but after his death the importance of his efforts was often played down by those who wished to show that the government had not acted quickly enough, or vigorously enough to control the hazard. The contention of this paper is that these criticisms are not justified and that Merewether acted to the best of his ability, given the conditions and knowledge current at the time he was working.}, } @article {pmid31682242, year = {2019}, author = {Świątkowska, B}, title = {[The occurrence of asbestos-related diseases among former employees of asbestos processing plants in Poland].}, journal = {Medycyna pracy}, volume = {70}, number = {6}, pages = {723-731}, doi = {10.13075/mp.5893.00890}, pmid = {31682242}, issn = {2353-1339}, mesh = {Adult ; Asbestos/*adverse effects ; Asbestosis/*epidemiology ; Female ; Humans ; Lung Neoplasms/*chemically induced ; Male ; Middle Aged ; Occupational Diseases/*epidemiology ; Occupational Exposure/*adverse effects/*statistics & numerical data ; Poland/epidemiology ; Population Surveillance ; }, abstract = {BACKGROUND: Despite the fact that asbestos is no longer used in production in Poland, there are still new cases of asbestos-related diseases among workers previously exposed to asbestos dust. This situation is related to the specificity of the biological activity of this mineral; the health consequences of asbestos can manifest not only during the exposure but also many years after exposure cessation. The aim of the analysis was to assess the occurrence of occupational diseases among people exposed to asbestos dust, who were examined under the Amiantus program.

MATERIAL AND METHODS: The research material consisted of the program cards filled by the doctors conducting the examinations as well as radiological images stored on the International Labour Organization form. The analysis covered 8049 people, including 37% of women surveyed in the years 2000-2017.

RESULTS: In the group of former employees of asbestos processing plants, the occupational disease was diagnosed in 1993 people (25%), including 584 women (19%). The most common was asbestosis (76% of occupational diseases) and pleural disease (17%). Malignant neoplasms accounted for 7% of all cases in this group. The analysis showed an increase in the incidence of respiratory system diseases along with the age of the surveyed persons, their seniority at asbestos processing plants and an increase in cumulative exposure. The chest radiographs revealed radiological changes among 75% of the examined cases, whereas the changes entitling to diagnose asbestosis, according to the criteria applicable in Poland, occurred in 23% of the workers. The adoption of international criteria would increase the incidence of asbestosis as an occupational disease by 19% in the study group.

CONCLUSIONS: The increase in the percentage of people with a diagnosed occupational disease provides evidence for the worsening health status of the former workers as well as a good detection of asbestos-related diseases among employees exposed to asbestos dust in the past. The results of the analysis indicate the need for undertaking a discussion in Poland on the implementation of international criteria for the diagnosis of asbestosis. Med Pr. 2019;70(6):723-31.}, } @article {pmid31671889, year = {2019}, author = {Wörthmüller, J and Salicio, V and Oberson, A and Blum, W and Schwaller, B}, title = {Modulation of Calretinin Expression in Human Mesothelioma Cells Reveals the Implication of the FAK and Wnt Signaling Pathways in Conferring Chemoresistance towards Cisplatin.}, journal = {International journal of molecular sciences}, volume = {20}, number = {21}, pages = {}, pmid = {31671889}, issn = {1422-0067}, mesh = {Antineoplastic Agents/*pharmacology ; Calbindin 2/genetics/*metabolism ; Carcinogenesis ; Carrier Proteins/metabolism ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Cisplatin/*pharmacology ; Down-Regulation ; Drug Resistance, Neoplasm/*drug effects ; Epithelial-Mesenchymal Transition/drug effects ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/*metabolism ; Mesothelioma/*metabolism ; Mesothelioma, Malignant ; Wnt Signaling Pathway/*drug effects ; }, abstract = {Malignant mesothelioma (MM) is an aggressive asbestos-linked neoplasm, characterized by dysregulation of signaling pathways. Due to intrinsic or acquired chemoresistance, MM treatment options remain limited. Calretinin is a Ca[2+]-binding protein expressed during MM tumorigenesis that activates the FAK signaling pathway, promoting invasion and epithelial-to-mesenchymal transition. Constitutive calretinin downregulation decreases MM cells' growth and survival, and impairs tumor formation in vivo. In order to evaluate early molecular events occurring during calretinin downregulation, we generated a tightly controlled IPTG-inducible expression system to modulate calretinin levels in vitro. Calretinin downregulation significantly reduced viability and proliferation of MM cells, attenuated FAK signaling and reduced the invasive phenotype of surviving cells. Importantly, surviving cells showed a higher resistance to cisplatin due to increased Wnt signaling. This resistance was abrogated by the Wnt signaling pathway inhibitor 3289-8625. In various MM cell lines and regardless of calretinin expression levels, blocking of FAK signaling activated the Wnt signaling pathway and vice versa. Thus, blocking both pathways had the strongest impact on MM cell proliferation and survival. Chemoresistance mechanisms in MM cells have resulted in a failure of single-agent therapies. Targeting of multiple components of key signaling pathways, including Wnt signaling, might be the future method-of-choice to treat MM.}, } @article {pmid31670764, year = {2020}, author = {Musk, AWB and Reid, A and Olsen, N and Hobbs, M and Armstrong, B and Franklin, P and Hui, J and Layman, L and Merler, E and Brims, F and Alfonso, H and Shilkin, K and Sodhi-Berry, N and de Klerk, N}, title = {The Wittenoom legacy.}, journal = {International journal of epidemiology}, volume = {49}, number = {2}, pages = {467-476}, doi = {10.1093/ije/dyz204}, pmid = {31670764}, issn = {1464-3685}, mesh = {*Asbestos, Crocidolite/toxicity ; Humans ; *Lung Neoplasms/epidemiology ; *Mining ; *Occupational Diseases/epidemiology ; *Occupational Exposure/adverse effects ; Western Australia/epidemiology ; }, abstract = {The Wittenoom crocidolite (blue asbestos) mine and mill ceased operating in 1966. The impact of this industry on asbestos-related disease in Western Australia has been immense. Use of the employment records of the Australian Blue Asbestos Company and records of the Wittenoom township residents has permitted two cohorts of people with virtually exclusive exposure to crocidolite to be assembled and studied. Follow-up of these two cohorts has been conducted through data linkage with available hospital, mortality and cancer records. The evolution of asbestos-related disease has been recorded and, with the establishment of exposure measurements, quantitative exposure-response relationships have been estimated. There has been an ongoing epidemic of mortality from lung cancer and malignant mesothelioma and, less so, from asbestosis. Wittenoom crocidolite was used extensively in asbestos-cement products in Western Australia. As a result, the state has recorded a higher malignant-mesothelioma mortality rate than in any other Australian state and in any defined general population in the world. Thus, the legacy of Wittenoom has extended beyond the mine and the town, and is still evident more than 50 years after the closure of the mine.}, } @article {pmid31670225, year = {2019}, author = {Cinausero, M and Rihawi, K and Cortiula, F and Follador, A and Fasola, G and Ardizzoni, A}, title = {Emerging therapies in malignant pleural mesothelioma.}, journal = {Critical reviews in oncology/hematology}, volume = {144}, number = {}, pages = {102815}, doi = {10.1016/j.critrevonc.2019.102815}, pmid = {31670225}, issn = {1879-0461}, mesh = {Combined Modality Therapy ; Humans ; Immunotherapy ; *Lung Neoplasms ; *Mesothelioma ; *Pleural Neoplasms ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare cancer of the pleural surfaces frequently related to asbestos exposure. It is characterized by a poor prognosis even for patients treated with trimodality therapy, including surgery, chemotherapy and radiotherapy. Moreover, the majority of patients are not candidates for surgery due to disease advanced stage or medical comorbidities. For these patients, the survival rate is even lower and few therapeutic options are currently available. Nevertheless, many interesting novel approaches are under investigation, among which immunotherapy represents one of the most promising emerging strategies. In this review, we will discuss the role of new therapeutic options, particularly immunotherapy, and present the results of the most important and promising clinical trials.}, } @article {pmid31667596, year = {2020}, author = {Minami, K and Jimbo, N and Tanaka, Y and Hokka, D and Miyamoto, Y and Itoh, T and Maniwa, Y}, title = {Malignant mesothelioma in situ diagnosed by methylthioadenosine phosphorylase loss and homozygous deletion of CDKN2A: a case report.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {476}, number = {3}, pages = {469-473}, pmid = {31667596}, issn = {1432-2307}, mesh = {Aged ; Biomarkers, Tumor/*analysis ; Cyclin-Dependent Kinase Inhibitor p16/analysis/genetics ; *Early Diagnosis ; Genes, p16 ; Humans ; Lung Neoplasms/*diagnosis ; Male ; Mesothelioma/*diagnosis ; Mesothelioma, Malignant ; Pleural Neoplasms/*diagnosis ; Purine-Nucleoside Phosphorylase/analysis/biosynthesis ; Sequence Deletion ; }, abstract = {Malignant pleural mesothelioma (MPM), associated with unfavorable outcomes, is closely associated with asbestos exposure. Early detection and treatment are critical to prolong survival of patients with MPM because of the rapid progression and resistance to treatment. The recently defined malignant mesothelioma in situ (MIS) has been gaining increasing attention with advances in genome-based methods including fluorescence in situ hybridization (FISH) as well as immunohistochemistry. We herein report the case of a MIS in a 73-year-old male with a history of asbestos exposure presenting with massive pleural effusion in the right thoracic cavity. Video-assisted thoracoscopic surgery with pleural biopsy of the right side revealed a single layer of atypical mesothelial cells without invasive lesions by hematoxylin and eosin staining. However, these mesothelial cells exhibited a loss of methylthioadenosine phosphorylase (MTAP) by immunohistochemistry and homozygous deletion of CDKN2A (p16) by FISH, leading to the diagnosis of MIS.}, } @article {pmid31662422, year = {2019}, author = {Reynolds, CJ and Minelli, C and Darnton, A and Cullinan, P}, title = {Mesothelioma mortality in Great Britain: how much longer will dockyards dominate?.}, journal = {Occupational and environmental medicine}, volume = {76}, number = {12}, pages = {908-912}, doi = {10.1136/oemed-2019-105878}, pmid = {31662422}, issn = {1470-7926}, support = {MR/S019669/1/MRC_/Medical Research Council/United Kingdom ; 201291/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Aged ; Female ; Humans ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; Mesothelioma, Malignant ; Occupational Diseases/*mortality ; *Ships ; United Kingdom/epidemiology ; }, abstract = {OBJECTIVES: We aimed to investigate whether there has been a geographic shift in the distribution of mesothelioma deaths in Great Britain given the decline of shipbuilding and progressive exposure regulation.

METHODS: We calculated age-adjusted mesothelioma mortality rates and estimated rate ratios for areas with and without a dockyard. We compared spatial autocorrelation statistics (Moran's I) for age-adjusted rates at local authority district level for 2002-2008 and 2009-2015. We measured the mean distance of the deceased's postcode to the nearest dockyard at district level and calculated the association of average distance to dockyard and district mesothelioma mortality using simple linear regression for men, for 2002-2008 and 2009-2015.

RESULTS: District age-adjusted male mortality rates fell during 2002-2015 for 80 of 348 districts (23%), rose for 267 (77%) and were unchanged for one district; having one or more dockyards in a district was associated with rates falling (OR=2.43, 95% CI 1.22 to 4.82, p=0.02). The mortality rate ratio for men in districts with a dockyard, compared with those without a dockyard was 1.41 (95% CI 1.35 to 1.48, p<0.05) for 2002-2008 and 1.18 (95% CI 1.13 to 1.23, p<0.05) for 2009-2015. Spatial autocorrelation (measured by Moran's I) decreased from 0.317 (95% CI 0.316 to 0.319, p=0.001) to 0.312 (95% CI 0.310 to 0.314, p=0.001) for men and the coefficient of the association between distance to dockyard and district level age-adjusted male mortality (per million population) from -0.16 (95% CI -0.21 to -0.10, p<0.01) to -0.13 (95% CI -0.18 to -0.07, p<0.01) for men, when comparing 2002-2008 with 2009-2015.

CONCLUSION: For most districts age-adjusted mesothelioma mortality rates increased through 2002-2015 but the relative contribution from districts with a dockyard fell. Dockyards remain strongly spatially associated with mesothelioma mortality but the strength of this association appears to be falling and mesothelioma deaths are becoming more dispersed.}, } @article {pmid31655816, year = {2020}, author = {Fortin, M and Cabon, E and Berbis, J and Laroumagne, S and Guinde, J and Elharrar, X and Dutau, H and Astoul, P}, title = {Diagnostic Value of Computed Tomography Imaging Features in Malignant Pleural Mesothelioma.}, journal = {Respiration; international review of thoracic diseases}, volume = {99}, number = {1}, pages = {28-34}, doi = {10.1159/000503239}, pmid = {31655816}, issn = {1423-0356}, mesh = {Aged ; Aged, 80 and over ; Breast Neoplasms/pathology ; Carcinoma, Squamous Cell/diagnostic imaging/secondary ; Female ; Humans ; Lung Neoplasms/pathology ; Male ; Mesothelioma, Malignant/*diagnostic imaging/pathology ; Middle Aged ; Neoplasms, Unknown Primary/pathology ; Pleural Effusion, Malignant/*diagnostic imaging/pathology ; Pleural Neoplasms/*diagnostic imaging/pathology/secondary ; Retrospective Studies ; Thoracentesis ; Thoracoscopy ; *Tomography, X-Ray Computed ; }, abstract = {BACKGROUND: Medical history, thoracentesis, and imaging features are usually the first steps in the investigation of a possible malignant pleural effusion (MPE). Unfortunately, the diagnostic yield of thoracentesis in this situation is suboptimal even if the procedure is repeated, especially in the context of malignant pleural mesothelioma (MPM). The next step for confirming the diagnosis, if clinically appropriate, is thoracoscopy, but not all patients are fit to undergo this procedure, so the diagnosis is then based on the medical history and imaging features only.

OBJECTIVES: Our objective was to evaluate the diagnostic value of the medical history and imaging features in MPM.

METHODS: We reviewed the imaging and medical charts of 92 patients with a final diagnosis of MPE included in our prospective medical thoracoscopy database. The clinical characteristics and imaging features of patients with primary MPE were compared with those of patients with secondary MPE.

RESULTS: Male sex (82 vs. 59%, p = 0.02), asbestos exposure (58 vs. 10%, p < 0.001), and mediastinal (68 vs. 33%, p = 0.04), diaphragmatic (75 vs. 31%, p = 0.001) and circumferential pleural thickening (55 vs. 19% p = 0.001) were significantly more frequent in MPM patients. In a multivariate linear regression model, only asbestos exposure (OR 11.2; 95% CI 3.4-36.9) and circumferential pleural thickening (OR 4.7; 95% CI 1.6-13.9) were significantly associated with a diagnosis of MPM.

CONCLUSION: In situations where it is impossible to obtain adequate pleural samples to differentiate MPM from a secondary pleural malignancy, the combination of circumferential pleural thickening and a history of asbestos exposure may be sufficient to make a clinical diagnosis.}, } @article {pmid31648983, year = {2019}, author = {Alcala, N and Mangiante, L and Le-Stang, N and Gustafson, CE and Boyault, S and Damiola, F and Alcala, K and Brevet, M and Thivolet-Bejui, F and Blanc-Fournier, C and Le Rochais, JP and Planchard, G and Rousseau, N and Damotte, D and Pairon, JC and Copin, MC and Scherpereel, A and Wasielewski, E and Wicquart, L and Lacomme, S and Vignaud, JM and Ancelin, G and Girard, C and Sagan, C and Bonnetaud, C and Hofman, V and Hofman, P and Mouroux, J and Thomas de Montpreville, V and Clermont-Taranchon, E and Mazieres, J and Rouquette, I and Begueret, H and Blay, JY and Lantuejoul, S and Bueno, R and Caux, C and Girard, N and McKay, JD and Foll, M and Galateau-Salle, F and Fernandez-Cuesta, L}, title = {Redefining malignant pleural mesothelioma types as a continuum uncovers immune-vascular interactions.}, journal = {EBioMedicine}, volume = {48}, number = {}, pages = {191-202}, pmid = {31648983}, issn = {2352-3964}, support = {001/WHO_/World Health Organization/International ; R01 CA120528/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers, Tumor ; *Disease Susceptibility ; Female ; Gene Expression Profiling ; Humans ; Immunohistochemistry ; Lung Neoplasms/*diagnosis/*etiology/pathology ; Male ; Mesothelioma/*diagnosis/*etiology/pathology ; Mesothelioma, Malignant ; Neovascularization, Pathologic/*immunology ; Pleural Neoplasms/*diagnosis/*etiology/pathology ; Transcriptome ; Tumor Microenvironment/*immunology ; }, abstract = {BACKGROUND: Malignant Pleural Mesothelioma (MPM) is an aggressive disease related to asbestos exposure, with no effective therapeutic options.

METHODS: We undertook unsupervised analyses of RNA-sequencing data of 284 MPMs, with no assumption of discreteness. Using immunohistochemistry, we performed an orthogonal validation on a subset of 103 samples and a biological replication in an independent series of 77 samples.

FINDINGS: A continuum of molecular profiles explained the prognosis of the disease better than any discrete model. The immune and vascular pathways were the major sources of molecular variation, with strong differences in the expression of immune checkpoints and pro-angiogenic genes; the extrema of this continuum had specific molecular profiles: a "hot" bad-prognosis profile, with high lymphocyte infiltration and high expression of immune checkpoints and pro-angiogenic genes; a "cold" bad-prognosis profile, with low lymphocyte infiltration and high expression of pro-angiogenic genes; and a "VEGFR2+/VISTA+" better-prognosis profile, with high expression of immune checkpoint VISTA and pro-angiogenic gene VEGFR2. We validated the gene expression levels at the protein level for a subset of five selected genes belonging to the immune and vascular pathways (CD8A, PDL1, VEGFR3, VEGFR2, and VISTA), in the validation series, and replicated the molecular profiles as well as their prognostic value in the replication series.

INTERPRETATION: The prognosis of MPM is best explained by a continuous model, which extremes show specific expression patterns of genes involved in angiogenesis and immune response.}, } @article {pmid32704189, year = {2019}, author = {Berry, D and Januch, J and Woodbury, L and Kent, D}, title = {Detection of Erionite and Other Zeolite Fibers in Soil by the Fluidized Bed Preparation Methodology.}, journal = {Microscope (Carshalton Beeches (Surrey))}, volume = {67}, number = {4}, pages = {147-158}, pmid = {32704189}, issn = {0026-282X}, support = {EPA999999/ImEPA/Intramural EPA/United States ; }, abstract = {Erionite is a zeolite mineral that can occur as fibrous particles in soil. Inhalation exposure to erionite fibers may result in increased risk of diseases, such as mesothelioma. Low level detection of mineral fibers in soils has traditionally been accomplished using polarized light microscopy (PLM) methods to analyze bulk samples providing detection limits of around 0.25% by weight. This detection level may not be sufficiently low enough for protection of human health and is subject to large variability between laboratories. The fluidized bed asbestos segregator (FBAS) soil preparation method uses air elutriation to separate mineral fibers, such as erionite, from soil particles with higher aerodynamic diameter and deposits those mineral fibers onto filters that can be quantitatively analyzed by microscopic techniques, such as transmission electron microscopy (TEM). In this study, performance evaluation (PE) standards of erionite in soil with nominal concentrations ranging from 0.1% to 0.0001% by weight were prepared using the FBAS soil preparation method and the resulting filters were analyzed by TEM. The analytical results of this study illustrate a linear relationship between the nominal concentration of erionite (as % by weight) in the PE standard and the concentration estimated by TEM analysis expressed as erionite structures per gram of test material (s/g). A method detection limit of 0.003% by weight was achieved, which is approximately 100 times lower than typical detection limits for soils by PLM. The FBAS soil preparation method was also used to evaluate authentic field soil samples to better estimate the concentrations of erionite in soils on a weight percent basis. This study demonstrates the FBAS preparation method, which has already been shown to reliably detect low levels of asbestos in soil, can also be used to quantify low levels of erionite in soil.}, } @article {pmid32464005, year = {2019}, author = {Bolognesi, C and Bruzzone, M and Fontana, V and Ugolini, D and Compalati, A and Stagnaro, L and Ceppi, M}, title = {The Role of Micronucleus Assay to Detect Genetic Instability in Respiratory Cancer Patients.}, journal = {Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer}, volume = {38}, number = {4}, pages = {345-352}, doi = {10.1615/JEnvironPatholToxicolOncol.2019030907}, pmid = {32464005}, issn = {2162-6537}, mesh = {Adult ; Biomarkers, Tumor/metabolism ; Female ; Genetic Predisposition to Disease ; Humans ; Lung Neoplasms/*genetics ; Male ; Mesothelioma/genetics ; Mesothelioma, Malignant ; *Micronucleus Tests ; Middle Aged ; }, abstract = {Asbestos represents the main risk factor for malignant pleural mesothelioma (PM) even if only a minority of exposed people develop this tumor, suggesting a significant role for genetic susceptibility. This study aims to evaluate micronuclei (MN) frequency as a biomarker of genome instability in peripheral blood lymphocytes of PM and lung cancer (LC) patients when compared with healthy controls (HCs) and patients with nonneoplastic respiratory diseases (RDs). Lymphocyte cytokinesis-block MN assay was carried out on 317 subjects. Mutagen sensitivity, measured by quantifying MN frequency after an in vitro challenge with ionizing radiation, was evaluated in 252 subjects. A significant increase in MN frequency was observed in cancer patients compared to HCs, with a mean ratio (MR) of 1.35 and 1.36 at baseline and 1.43 and 1.38 after irradiation in PM and LC patients, respectively. A positive (synergistic) interaction between asbestos exposure and disease status was observed for MN frequency after irradiation in PM patients with possible exposure to asbestos (MR = 1.62). The evidence of increased genetic damage in cancer cases confirms lymphocyte cytokinesis-block MN assay as a sensitive predictor of the role of genetic instability in carcinogenic processes.}, } @article {pmid31632972, year = {2019}, author = {Johnson, TG and Schelch, K and Mehta, S and Burgess, A and Reid, G}, title = {Why Be One Protein When You Can Affect Many? The Multiple Roles of YB-1 in Lung Cancer and Mesothelioma.}, journal = {Frontiers in cell and developmental biology}, volume = {7}, number = {}, pages = {221}, pmid = {31632972}, issn = {2296-634X}, abstract = {Lung cancers and malignant pleural mesothelioma (MPM) have some of the worst 5-year survival rates of all cancer types, primarily due to a lack of effective treatment options for most patients. Targeted therapies have shown some promise in thoracic cancers, although efficacy is limited only to patients harboring specific mutations or target expression. Although a number of actionable mutations have now been identified, a large population of thoracic cancer patients have no therapeutic options outside of first-line chemotherapy. It is therefore crucial to identify alternative targets that might lead to the development of new ways of treating patients diagnosed with these diseases. The multifunctional oncoprotein Y-box binding protein-1 (YB-1) could serve as one such target. Recent studies also link this protein to many inherent behaviors of thoracic cancer cells such as proliferation, invasion, metastasis and involvement in cancer stem-like cells. Here, we review the regulation of YB-1 at the transcriptional, translational, post-translational and sub-cellular levels in thoracic cancer and discuss its potential use as a biomarker and therapeutic target.}, } @article {pmid31624358, year = {2019}, author = {Nowak, AK and Forde, PM}, title = {Immunotherapy trials in mesothelioma - promising results, but don't stop here.}, journal = {Nature reviews. Clinical oncology}, volume = {16}, number = {12}, pages = {726-728}, pmid = {31624358}, issn = {1759-4782}, mesh = {Humans ; Immunotherapy ; *Lung Neoplasms ; *Mesothelioma ; }, } @article {pmid31619883, year = {2019}, author = {Munot, MN and Utpat, KV and Desai, UD and Joshi, JM}, title = {Malignant Mesothelioma - Report of Two Cases with Different Presentations.}, journal = {Indian journal of occupational and environmental medicine}, volume = {23}, number = {2}, pages = {93-96}, pmid = {31619883}, issn = {0973-2284}, abstract = {Malignant pleural mesothelioma (MPM) is a rare and aggressive neoplasm that stems from the mesothelial cells lining the visceral cavities, namely, the pleura, peritoneum, pericardium, and tunica vaginalis of the testes. MPM is the most common variant of these and constitutes up to 80% of all malignant mesotheliomas. It is usually associated with asbestos exposure and is a locally invasive neoplasm that spreads along pleura and can involve lungs with locoregional metastasis. Diagnosis remains challenging due to the latency between asbestos exposure and clinical presentation and the variable clinicoradiological manifestations. Meticulous history taking, high index of, suspicion and multimodality approach toward diagnosis are the keys to better prognosis. We hereby present two interesting cases of MPM with different presentations.}, } @article {pmid31610664, year = {2019}, author = {Levý, M and Boublíková, L and Büchler, T and Šimša, J}, title = {Treatment of Malignant Peritoneal Mesothelioma.}, journal = {Klinicka onkologie : casopis Ceske a Slovenske onkologicke spolecnosti}, volume = {32}, number = {5}, pages = {333-337}, doi = {10.14735/amko2019333}, pmid = {31610664}, issn = {1802-5307}, mesh = {Combined Modality Therapy ; *Cytoreduction Surgical Procedures ; Humans ; *Hyperthermia, Induced ; Mesothelioma/diagnosis/epidemiology/*therapy ; Peritoneal Neoplasms/diagnosis/epidemiology/*therapy ; }, abstract = {Malignant mesothelioma is a highly malignant disease that most often occurs in the pleura of the thoracic cavity, followed by the peritoneum, pericardium, or tinea vaginalis testis. Malignant peritoneal mesothelioma (MPM) accounts for 10-15% of all mesotheliomas. The most significant risk factor for MPM is exposure to asbestos. There is no specific symptomatology, and imaging (computed tomography) and histopathology are crucial for diagnosis. There are no generally accepted guidelines for radical treatment of MPM. Previously, the prognosis of MPM patients was poor, with survival of up to 1 year. However, median survival of patients who are suitable candidates for radical therapy is currently 3-5 years. A combination of cytoreductive surgery (CRS) and hyperthermic perioperative chemotherapy (HIPEC) is recommended in selected patients, while chemotherapy alone has insufficient efficacy. Systemic chemotherapy remains the only treatment option for patients who are unsuitable for CRS and HIPEC. In selected patients scheduled for or currently undergoing CRS and HIPEC, surgery may be performed in combination with systemic chemotherapy in the neoadjuvant or adjuvant setting; however, the benefit is unclear. There are no recommendations for follow-up of MPM patients after radical surgery. Existing guidelines for the pleural form (e.g., those issued by the European Society for Medical Oncology) do not specify the frequency or method of investigation. In the absence of specific serum markers, only CA 125 and mesothelin are generally available. Imaging methods include ultrasonography, computed tomography, and magnetic resonance imaging.}, } @article {pmid31609780, year = {2020}, author = {Moline, J and Bevilacqua, K and Alexandri, M and Gordon, RE}, title = {Mesothelioma Associated With the Use of Cosmetic Talc.}, journal = {Journal of occupational and environmental medicine}, volume = {62}, number = {1}, pages = {11-17}, doi = {10.1097/JOM.0000000000001723}, pmid = {31609780}, issn = {1536-5948}, mesh = {*Asbestos ; *Cosmetics ; Humans ; Mesothelioma/chemically induced/*epidemiology ; Mesothelioma, Malignant ; *Talc ; }, abstract = {OBJECTIVE: To describe 33 cases of malignant mesothelioma among individuals with no known asbestos exposure other than cosmetic talcum powder.

METHODS: Cases were referred for medico-legal evaluation, and tissue digestions were performed in some cases. Tissue digestion for the six cases described was done according to standard methodology.

RESULTS: Asbestos of the type found in talcum powder was found in all six cases evaluated. Talcum powder usage was the only source of asbestos for all 33 cases.

CONCLUSIONS: Exposure to asbestos-contaminated talcum powders can cause mesothelioma. Clinicians should elicit a history of talcum powder usage in all patients presenting with mesothelioma.}, } @article {pmid31596154, year = {2019}, author = {Ceresoli, GL and Rossi, A}, title = {Approved and emerging treatments of malignant pleural mesothelioma in elderly patients.}, journal = {Expert review of respiratory medicine}, volume = {13}, number = {12}, pages = {1179-1188}, doi = {10.1080/17476348.2019.1678386}, pmid = {31596154}, issn = {1747-6356}, mesh = {Aged ; Combined Modality Therapy ; Humans ; *Immunotherapy ; Lung Neoplasms/*drug therapy/therapy ; Mesothelioma/*drug therapy/therapy ; Mesothelioma, Malignant ; Pleural Neoplasms/*drug therapy/therapy ; Treatment Outcome ; }, abstract = {Introduction: Malignant pleural mesothelioma (MPM) is a rare neoplasm with asbestos exposure as the dominant etiologic agent. Owing to the long latent period following exposure, MPM is often diagnosed late in life. Despite this, elderly patients are under-represented in clinical trials. To date, data regarding the tolerability and efficacy of anticancer treatments for elderly patients affected by MPM are still lacking.Areas covered: The current state-of-the-art of approved treatments employed in the treatment of MPM elderly patients is reviewed and discussed, with a look to emerging therapies. A structured search of bibliographic databases for peer-reviewed research literature and of main meeting abstracts using a focused review question was undertaken.Expert opinion: Even though the median age of MPM patients enrolled in the most recent experimental trials is increasing, no specific analysis has been reported so far in the elderly. Moreover, no data are available for the 'oldest of the elderly' (>75 years). Treatment of elderly patients with MPM is one of the major challenges to the clinician. There is a clear need of large, well-conducted retrospective studies and above all of prospective investigations in this patient population, both in the first-and in the second-line setting.}, } @article {pmid31594840, year = {2019}, author = {Kwak, K and Paek, D and Zoh, KE}, title = {Exposure to asbestos and the risk of colorectal cancer mortality: a systematic review and meta-analysis.}, journal = {Occupational and environmental medicine}, volume = {76}, number = {11}, pages = {861-871}, doi = {10.1136/oemed-2019-105735}, pmid = {31594840}, issn = {1470-7926}, mesh = {Asbestos/*toxicity ; Cohort Studies ; Colorectal Neoplasms/*epidemiology/*mortality ; Female ; Hazardous Substances/*toxicity ; Humans ; Lung Neoplasms/epidemiology ; Male ; Occupational Exposure/*statistics & numerical data ; Risk Factors ; }, abstract = {Asbestos exposure is associated with mesothelioma and cancer of the lung, larynx and ovary. However, the association between asbestos exposure and colorectal cancer is controversial despite several systematic reviews of the literature, including a number of meta-analyses. We performed a systematic review and meta-analysis to evaluate quantitatively the association between exposure to asbestos and colorectal cancer. We searched for articles on occupational asbestos exposure and colorectal cancer in PubMed, EMBASE and Web of Science published before April 2018. In total, 44 articles were selected and 46 cohort studies were analysed. The overall pooled risk estimates and corresponding 95% CIs of the association between occupational asbestos exposure and colorectal cancer were calculated using a random-effects model. Subgroup analyses and sensitivity tests were also performed. There was a significantly increased risk of colorectal cancer mortality among workers exposed to asbestos occupationally, with an overall pooled SMR of 1.16 (95% CI: 1.05 to 1.29). The pooled SMR for colorectal cancer was elevated in studies in which the asbestos-associated risk of lung cancer was also elevated (1.43; 95% CI: 1.30 to 1.56). This implies that the risk of colorectal cancer mortality increases as the level of asbestos exposure rises. A sensitivity analysis showed robust results and there was no publication bias. Although the effect size was small and the heterogeneity among studies was large, our findings indicate that occupational exposure to asbestos is a risk factor for colorectal cancer.}, } @article {pmid31564247, year = {2019}, author = {Vimercati, L and Cavone, D and Caputi, A and Delfino, MC and De Maria, L and Ferri, GM and Serio, G}, title = {Malignant mesothelioma in construction workers: the Apulia regional mesothelioma register, Southern Italy.}, journal = {BMC research notes}, volume = {12}, number = {1}, pages = {636}, pmid = {31564247}, issn = {1756-0500}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Construction Industry/instrumentation ; Environmental Exposure/*adverse effects ; Humans ; Incidence ; Italy/epidemiology ; Lung/drug effects/pathology ; Lung Neoplasms/chemically induced/diagnosis/*epidemiology/pathology ; Male ; Mesothelioma/chemically induced/diagnosis/*epidemiology/pathology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/*adverse effects ; *Registries ; }, abstract = {OBJECTIVE: Asbestos was widely used in construction in both a friable and a compact form until the 1990s, before its use was banned. Today, many of these materials are still in situ and represent a source of risk for construction workers. The objective of the study was to analyse the cases of mesothelioma arising among construction workers registered in the Apulia regional register of mesothelioma.

RESULTS: For the period 1993-2018, there were 178 male cases, and 10.2% of the cases were present in the regional register. The average age at diagnosis was 64.7 years. The site was pleural in 96.06% of cases, with a diagnosis of certainty in 86.5% of the total cases and 61.8% of cases with epithelial histology. The average latency is 43.9 years. In 75.2% of cases, the exposure began between 1941 and 1970, with an average duration of 24.3 years. The age at the start of exposure in 68.5% of cases is between 8 and 20 years. The ORs were 2.5 (C.I. 95% 1.01-6.17) for the epithelioid histotype and the high duration of exposure. The data underline the need for prevention and information on all activities involving construction workers in which asbestos-containing materials are still used.}, } @article {pmid31557561, year = {2019}, author = {Takeda, M and Ohe, Y and Horinouchi, H and Hida, T and Shimizu, J and Seto, T and Nosaki, K and Kishimoto, T and Miyashita, I and Yamada, M and Kaneko, Y and Morimoto, C and Nakagawa, K}, title = {Phase I study of YS110, a recombinant humanized monoclonal antibody to CD26, in Japanese patients with advanced malignant pleural mesothelioma.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {137}, number = {}, pages = {64-70}, doi = {10.1016/j.lungcan.2019.09.010}, pmid = {31557561}, issn = {1872-8332}, mesh = {Adult ; Aged ; Antibodies, Monoclonal/pharmacokinetics/*therapeutic use ; Cohort Studies ; Dipeptidyl Peptidase 4/immunology ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/*drug therapy/immunology/pathology ; Male ; Maximum Tolerated Dose ; Mesothelioma/*drug therapy/immunology/pathology ; Mesothelioma, Malignant ; Middle Aged ; Neoplasm Staging ; Pleural Neoplasms/*drug therapy/immunology/pathology ; Prognosis ; Response Evaluation Criteria in Solid Tumors ; Tissue Distribution ; Young Adult ; }, abstract = {OBJECTIVES: CD26 is a transmembrane glycoprotein with dipeptidyl peptidase IV activity that is overexpressed in malignant pleural mesothelioma (MPM). We performed a phase I study to determine the maximum tolerated dose, pharmacokinetics, and antitumor activity of YS110, a monoclonal antibody to CD26, in Japanese patients with MPM intolerant of or refractory to prior standard therapies.

MATERIAL AND METHODS: The study was designed as an open-label, 3 + 3 dose-escalation, phase I trial. Patients were sequentially assigned to three dosing cohorts (2, 4, or 6 mg/kg). Each 6-week treatment cycle consisted of YS110 administration weekly for 5 weeks followed by a 1-week rest period. Treatment was continued until disease progression, death, or intolerable toxicity. Corticosteroid, antihistamine, and acetaminophen administration before each infusion was adopted to limit infusion-related reactions (IRRs).

RESULTS: Nine Japanese patients (seven men and two women, mean age of 62.2 years), three in each dosing cohort, were enrolled in the study. No patient developed a dose-limiting toxicity. Adverse events of grade 3 or 4 developed in seven patients, with the most common such event being a decreased lymphocyte count. Two patients had mild or moderate IRRs. The serum concentration of YS110 increased in a dose-dependent manner. Among seven patients evaluable for tumor response, four showed stable disease and one achieved a partial response.

CONCLUSIONS: YS110 showed promising antitumor efficacy and was generally well tolerated in Japanese patients with advanced MPM at doses of up to 6 mg/kg. YS110 will be tested at 6 mg/kg in a subsequent phase II study.}, } @article {pmid31546009, year = {2020}, author = {Hinz, TK and Heasley, LE}, title = {Translating mesothelioma molecular genomics and dependencies into precision oncology-based therapies.}, journal = {Seminars in cancer biology}, volume = {61}, number = {}, pages = {11-22}, doi = {10.1016/j.semcancer.2019.09.014}, pmid = {31546009}, issn = {1096-3650}, mesh = {Animals ; Biomarkers, Tumor ; Combined Modality Therapy ; Gene Expression Profiling/methods ; Genetic Association Studies ; Genetic Predisposition to Disease ; *Genomics/methods ; Humans ; Loss of Function Mutation ; Mesothelioma/diagnosis/*etiology/*therapy ; Mesothelioma, Malignant/diagnosis/etiology/therapy ; Mutation ; *Precision Medicine/methods ; Receptor, Fibroblast Growth Factor, Type 1/genetics ; *Translational Research, Biomedical/methods ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare, yet lethal asbestos-induced cancer and despite marked efforts to reduce occupational exposure, the incidence has not yet significantly declined. Since 2003, combined treatment with a platinum-based agent and pemetrexed has been the first-line therapy and no effective or approved second-line treatments have emerged. The seemingly slow advance in developing new MPM treatments does not appear to be related to a low level of clinical and pre-clinical research activity. Rather, we suggest that a key hurdle in successfully translating basic discovery into novel MPM therapeutics is the underlying assumption that as a rare cancer, it will also be molecularly and genetically homogeneous. In fact, lung adenocarcinoma and melanoma only benefitted from precision oncology upon full appreciation of the high degree of molecular heterogeneity inherent in these cancers, especially regarding the diversity of oncogenic drivers. Herein, we consider the recent explosion of molecular and genetic information that has become available regarding MPM and suggest ways in which the unfolding landscape may guide identification of novel therapeutic vulnerabilities within subsets of MPM that can be targeted in a manner consistent with the tenets of precision oncology.}, } @article {pmid31538797, year = {2019}, author = {Geyer, SJ}, title = {Malignant Mesothelioma and Its Nonasbestos Causes: Talcum Powder Does Not Create Occult Asbestos Exposure.}, journal = {Archives of pathology & laboratory medicine}, volume = {143}, number = {12}, pages = {1439}, doi = {10.5858/arpa.2019-0388-LE}, pmid = {31538797}, issn = {1543-2165}, mesh = {*Asbestos ; Humans ; *Lung Neoplasms ; *Mesothelioma ; Talc ; }, } @article {pmid31534051, year = {2019}, author = {Hamaidia, M and Gazon, H and Hoyos, C and Hoffmann, GB and Louis, R and Duysinx, B and Willems, L}, title = {Inhibition of EZH2 methyltransferase decreases immunoediting of mesothelioma cells by autologous macrophages through a PD-1-dependent mechanism.}, journal = {JCI insight}, volume = {4}, number = {18}, pages = {}, pmid = {31534051}, issn = {2379-3708}, mesh = {Animals ; Antineoplastic Agents, Immunological/pharmacology/therapeutic use ; Cell Communication/*immunology ; Cell Culture Techniques ; Cell Line, Tumor/transplantation ; Coculture Techniques ; Disease Models, Animal ; Enhancer of Zeste Homolog 2 Protein/antagonists & inhibitors/genetics/immunology/*metabolism ; Humans ; Immunogenic Cell Death/drug effects/genetics ; Lung Neoplasms/*immunology/therapy ; Macrophages/*immunology/metabolism/transplantation ; Male ; Mesothelioma/*immunology/therapy ; Mesothelioma, Malignant ; Mice ; Peroxynitrous Acid/metabolism ; Programmed Cell Death 1 Receptor/antagonists & inhibitors/*immunology ; RAW 264.7 Cells/transplantation ; RNA, Small Interfering/metabolism ; Reactive Oxygen Species/metabolism ; }, abstract = {The roles of macrophages in orchestrating innate immunity through phagocytosis and T lymphocyte activation have been extensively investigated. Much less understood is the unexpected role of macrophages in direct tumor regression. Tumoricidal macrophages can indeed manifest cancer immunoediting activity in the absence of adaptive immunity. We investigated direct macrophage cytotoxicity in malignant pleural mesothelioma, a lethal cancer that develops from mesothelial cells of the pleural cavity after occupational asbestos exposure. In particular, we analyzed the cytotoxic activity of mouse RAW264.7 macrophages upon cell-cell contact with autologous AB1/AB12 mesothelioma cells. We show that macrophages killed mesothelioma cells by oxeiptosis via a mechanism involving enhancer of zeste homolog 2 (EZH2), a histone H3 lysine 27-specific (H3K27-specific) methyltransferase of the polycomb repressive complex 2 (PRC2). A selective inhibitor of EZH2 indeed impaired RAW264.7-directed cytotoxicity and concomitantly stimulated the PD-1 immune checkpoint. In the immunocompetent BALB/c model, RAW264.7 macrophages pretreated with the EZH2 inhibitor failed to control tumor growth of AB1 and AB12 mesothelioma cells. Blockade of PD-1 engagement restored macrophage-dependent antitumor activity. We conclude that macrophages can be directly cytotoxic for mesothelioma cells independent of phagocytosis. Inhibition of the PRC2 EZH2 methyltransferase reduces this activity because of PD-1 overexpression. Combination of PD-1 blockade and EZH2 inhibition restores macrophage cytotoxicity.}, } @article {pmid31525810, year = {2019}, author = {Kim, RY and Sterman, DH and Haas, AR}, title = {Malignant Mesothelioma: Has Anything Changed?.}, journal = {Seminars in respiratory and critical care medicine}, volume = {40}, number = {3}, pages = {347-360}, doi = {10.1055/s-0039-1693406}, pmid = {31525810}, issn = {1098-9048}, mesh = {Antineoplastic Agents, Immunological/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Asbestos/adverse effects ; Biomarkers, Tumor ; Biopsy ; CTLA-4 Antigen/antagonists & inhibitors ; Catheters, Indwelling ; Combined Modality Therapy ; Humans ; Immunohistochemistry ; Lung Neoplasms/diagnosis/pathology/*therapy ; Mesothelioma/diagnosis/pathology/*therapy ; Mesothelioma, Malignant ; Neoplasm Staging ; Pleural Neoplasms/diagnosis/pathology/*therapy ; Pneumonectomy/methods ; Prognosis ; Programmed Cell Death 1 Receptor/antagonists & inhibitors ; Radiotherapy, Adjuvant ; Thoracoscopy ; }, abstract = {Malignant pleural mesothelioma is a rare cancer associated with asbestos exposure and portends a dismal prognosis. Its worldwide incidence has been increasing, and treatment options are currently suboptimal and noncurative. However, since the turn of the century, several encouraging steps have been made toward improving outcomes for mesothelioma patients. An increased understanding of disease pathophysiology has led to more accurate diagnosis and staging, and the establishment of the standard of care first-line pemetrexed/platin doublet chemotherapy regimen in 2003 initially revolutionized treatment. While significant debate remains regarding the preferred approach to surgical and radiation therapy in the context of multimodal therapy, recent breakthroughs in immunotherapy offer hope for another paradigm shift in the near future. This review will summarize the current clinical approach to diagnosis, staging, and treatment of malignant pleural mesothelioma.}, } @article {pmid31511437, year = {2020}, author = {Huang, Q and Lan, YJ}, title = {Colorectal cancer and asbestos exposure-an overview.}, journal = {Industrial health}, volume = {58}, number = {3}, pages = {200-211}, pmid = {31511437}, issn = {1880-8026}, mesh = {Asbestos/*adverse effects ; Cohort Studies ; Colorectal Neoplasms/*mortality ; Construction Materials/adverse effects ; Humans ; Incidence ; Lung Neoplasms/mortality ; Mesothelioma/mortality ; Occupational Exposure/*adverse effects ; Textile Industry/statistics & numerical data ; }, abstract = {The relationship between colorectal cancer and asbestos exposure has not been fully clarified. This study aimed to determine the associations between asbestos exposure and colorectal cancer. We performed a meta-analysis to quantitatively evaluate this association. A fixed effects model was used to summarize the relative risks across studies. Sources of heterogeneity were explored through subgroup analyses and meta-regression. We analyzed the dose-effect relationship using lung cancer standardized mortality ratio (SMR) and the risk of mesothelioma as a percent (%) as exposure surrogates. A total of 47 cohort studies were included. We identified 28 incidence cohort studies from 17 separate papers and extracted colorectal cancer standardized incidence ratio (SIR). Cancer mortality data were extracted from 19 separate cohorts among 13 papers. The overall colorectal cancer SMR for synthesis cohort was 1.07 (95% CI 1.02-1.12). Statistically significant excesses were observed in exposure to mixed asbestos (SMR/SIR=1.07), exposure to production (SMR/SIR=1.11), among asbestos cement workers (SMR/SIR=1.18) and asbestos textile workers (SMR/SIR=1.11). Additionally, we determined that the SMR for lung cancer increased with increased exposure to asbestos, as did the risk for colorectal cancer. This study confirms that colorectal cancer has a positive weak associations with asbestos exposure.}, } @article {pmid31485011, year = {2020}, author = {Marchevsky, AM and Khoor, A and Walts, AE and Nicholson, AG and Zhang, YZ and Roggli, V and Carney, J and Roden, AC and Tazelaar, HD and Larsen, BT and LeStang, N and Chirieac, LR and Klebe, S and Tsao, MS and De Perrot, M and Pierre, A and Hwang, DM and Hung, YP and Mino-Kenudson, M and Travis, W and Sauter, J and Beasley, MB and Galateau-Sallé, F}, title = {Localized malignant mesothelioma, an unusual and poorly characterized neoplasm of serosal origin: best current evidence from the literature and the International Mesothelioma Panel.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {33}, number = {2}, pages = {281-296}, pmid = {31485011}, issn = {1530-0285}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biopsy ; Child ; Diagnosis, Differential ; Evidence-Based Medicine ; Female ; Humans ; Male ; Mesothelioma, Malignant/diagnostic imaging/mortality/*pathology/therapy ; Middle Aged ; Pleural Neoplasms/diagnostic imaging/mortality/*pathology/therapy ; Predictive Value of Tests ; Prognosis ; Solitary Fibrous Tumor, Pleural/diagnostic imaging/mortality/*pathology/therapy ; Tumor Burden ; Young Adult ; }, abstract = {Localized malignant mesotheliomas (LMM) is an uncommon and poorly recognized neoplasm. Its pathologic diagnosis is often surprising in patients with serosal/subserosal based localized tumors that are clinically suspicious for metastatic lesions or primary sarcomas. Once a tumor is diagnosed as "mesothelioma", LMM is often mistaken for diffuse malignant mesothelioma (DMM). Best currently available evidence about LMM was collected from the literature and cases diagnosed by members of the International Mesothelioma Panel (IMP). One hundred and one (101) LMM have been reported in the English literature. Patients had localized tumors with identical histopathologic features to DMM. Patients ranged in age from 6 to 82 years; 75% were men. Most (82%) of the tumors were intrathoracic. Others presented as intrahepatic, mesenteric, gastric, pancreatic, umbilical, splenic, and abdominal wall lesions. Tumors varied in size from 0.6 to 15 cm. Most patients underwent surgical resection and/or chemotherapy or radiation therapy. Median survival in a subset of patients was 29 months. Seventy two additional LMM from IMP institutions ranged in age from 28 to 95 years; 58.3% were men. Sixty tumors (83.3%) were intrathoracic, others presented in intraabdominal sites. Tumors varied in size from 1.2 to 19 cm. Median survival for 51 cases was 134 months. Best evidence was used to formulate guidelines for the diagnosis of LMM. It is important to distinguish LMM from DMM as their treatment and prognosis is different. A multidisciplinary approach is needed for the diagnosis of LMM as it shows identical histopathology and immunophenotype to DMM.}, } @article {pmid31477126, year = {2019}, author = {Abdelgied, M and El-Gazzar, AM and Alexander, WT and Numano, T and Iigou, M and Naiki-Ito, A and Takase, H and Hirose, A and Taquahashi, Y and Kanno, J and Abdelhamid, M and Abdou, KA and Takahashi, S and Alexander, DB and Tsuda, H}, title = {Carcinogenic effect of potassium octatitanate (POT) fibers in the lung and pleura of male Fischer 344 rats after intrapulmonary administration.}, journal = {Particle and fibre toxicology}, volume = {16}, number = {1}, pages = {34}, pmid = {31477126}, issn = {1743-8977}, mesh = {Animals ; Carcinogens/chemistry/pharmacokinetics/*toxicity ; Inhalation Exposure ; Lung/*drug effects/pathology ; Lung Neoplasms/*chemically induced/pathology ; Male ; Mesothelioma/*chemically induced/pathology ; Mesothelioma, Malignant ; Mineral Fibers ; Pleura/*drug effects/pathology ; Rats, Inbred F344 ; Surface Properties ; Tissue Distribution ; Titanium/chemistry/pharmacokinetics/*toxicity ; }, abstract = {BACKGROUND: Potassium octatitanate fibers (K2O•8TiO2, POT fibers) are used as an asbestos substitute. Their physical characteristics suggest that respirable POT fibers are likely to be carcinogenic in the lung and pleura. However, previous 2-year inhalation studies reported that respired POT fibers had little or no carcinogenic potential. In the present study ten-week old male F344 rats were left untreated or were administered vehicle, 0.25 or 0.5 mg rutile-type nano TiO2 (r-nTiO2), 0.25 or 0.5 mg POT fibers, or 0.5 mg MWCNT-7 by intra-tracheal intra-pulmonary spraying (TIPS), and then observed for 2 years.

RESULTS: There were no differences between the r-nTiO2 and control groups. The incidence of bronchiolo-alveolar cell hyperplasia was significantly increased in the groups treated with 0.50 mg POT and 0.50 mg MWCNT-7. The overall incidence of lung tumors, however, was not increased in either the POT or MWCNT-7 treated groups. Notably, the carcinomas that developed in the POT and MWCNT-7 treated rats were accompanied by proliferative fibrous connective tissue while the carcinomas that developed in the untreated rats and the r-nTiO2 treated rats were not (carcinomas did not develop in the vehicle control rats). In addition, the carcinoma that developed in the rat treated with 0.25 mg POT was a squamous cell carcinoma, a tumor that develops spontaneously in about 1 per 1700 rats. The incidence of mesothelial cell hyperplasia was 4/17, 7/16, and 10/14 and the incidence of malignant mesothelioma was 3/17, 1/16, and 2/14 in the 0.25 mg POT, 0.5 mg POT, and MWCNT-7 treated groups, respectively. Neither mesothelial cell hyperplasia nor mesothelioma developed in control rats or the rats treated with r-nTiO2. Since the incidence of spontaneously occurring malignant mesothelioma in rats is extremely low, approximately 1 per 1000 animals (Japan Bioassay Research Center [JBRC] historical control data), the development of multiple malignant mesotheliomas in the POT and MWCNT-7 treated groups was biologically significant.

CONCLUSION: The incidence of pleural mesotheliomas in male F344 rats administered POT fibers and MWCNT-7 was significantly higher than the JBRC historical control data, indicating that the incidence of pleural mesothelioma in the groups administered POT fibers and MWCNT-7 fibers via the airway using TIPS was biologically significant. The incidence of type II epithelial cell hyperplasia and the histology of the carcinomas that developed in the POT treated rats also indicates that respirable POT fibers are highly likely to be carcinogenic in the lungs of male F344 rats.}, } @article {pmid31475103, year = {2019}, author = {Cavallari, I and Urso, L and Sharova, E and Pasello, G and Ciminale, V}, title = {Liquid Biopsy in Malignant Pleural Mesothelioma: State of the Art, Pitfalls, and Perspectives.}, journal = {Frontiers in oncology}, volume = {9}, number = {}, pages = {740}, pmid = {31475103}, issn = {2234-943X}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive tumor linked to asbestos exposure. Although the risk factors for MPM are well-known, the majority of MPM patients are diagnosed at an advanced stage and have a very poor prognosis. Circulating biomarkers for early diagnosis remain to be identified, and the current standard for MPM diagnosis relies on pleural biopsies. Robust non-invasive tests for the screening of asbestos-exposed subjects are therefore an important unmet clinical need. This review provides a critical summary of recent liquid biopsy-based studies aimed at discovering novel blood-based circulating biomarkers for the early diagnosis and prognostic stratification of MPM patients.}, } @article {pmid31470859, year = {2019}, author = {Vimercati, L and Cavone, D and Delfino, MC and De Maria, L and Caputi, A and Ferri, GM and Serio, G}, title = {Asbestos exposure and malignant mesothelioma of the tunica vaginalis testis: a systematic review and the experience of the Apulia (southern Italy) mesothelioma register.}, journal = {Environmental health : a global access science source}, volume = {18}, number = {1}, pages = {78}, pmid = {31470859}, issn = {1476-069X}, mesh = {Asbestos/*adverse effects ; Humans ; Incidence ; Italy/epidemiology ; Lung Neoplasms/chemically induced/*epidemiology ; Male ; Mesothelioma/chemically induced/*epidemiology ; Mesothelioma, Malignant ; Occupational Diseases/chemically induced/*epidemiology ; Occupational Exposure/*adverse effects ; Registries/*statistics & numerical data ; Testicular Neoplasms/chemically induced/*epidemiology ; }, abstract = {BACKGROUND: Malignant mesothelioma of the tunica vaginalis testis (MMTVT) is a rare disease with a poor prognosis. The diagnosis and management of these lesions are often difficult for pathologists, surgeons, oncologists and occupational physicians. A preoperative diagnosis of malignancy is rarely made, and there is no established effective therapy except orchidectomy.

METHODS: A systematic literature review was conducted among the articles published in the English literature on primary MMTVT. Moreover four cases from the Apulia mesothelioma register are reported here.

RESULTS: Two hundred eighty-nine cases of MMTVT have been reported from 1943 to 2018. Overall asbestos exposure has been investigated only for 58% of all cases reported in this review, while in 41.8% this data are not available. Noteworthy is the fact that in many reports there is not an anamnestic reconstruction of any asbestos exposure. A history of direct occupational, environmental or familial asbestos exposure is found in 27.6% of the cases. The four cases from the Apulia mesothelioma register are all with ascertained occupational exposure to asbestos.

CONCLUSIONS: The true incidence of asbestos exposure in MMTVT is underestimated because of insufficient information reported in older literature. To establish a broad consensus on the causal relationship between asbestos and MMTVT in the scientific community its necessary to analyze the same variables in the epidemiological studies. In general it should be recommended that a positive history of exposure to asbestos or to asbestos-containing materials are at risk for the development of a MMTVT and should be monitored.}, } @article {pmid31467759, year = {2019}, author = {Hassan, D and Ligato, S}, title = {Localized Biphasic Malignant Peritoneal Mesothelioma with Rhabdoid Features Involving the Liver: Case Report and Review of the Literature.}, journal = {Case reports in pathology}, volume = {2019}, number = {}, pages = {2732674}, pmid = {31467759}, issn = {2090-6781}, abstract = {INTRODUCTION: Localized malignant mesotheliomas, defined as sharply circumscribed tumors of the serosal membrane with the microscopic appearance of diffuse malignant mesothelioma, are rare tumors; their behavior and prognosis are uncertain. Intrahepatic mesotheliomas are postulated to arise from mesothelial cells of Glisson's capsule.

CASE PRESENTATION: A 69-year-old female with no history of asbestos exposure presented with a one-month history of increasing abdominal pain associated with constitutional symptoms. Computerized Tomography (CT) scan of the abdomen and pelvis revealed a sizable soft tissue mass within the right paracolic gutter, abutting the inferior hepatic margin, the lateral abdominal wall, and descending colon. Ultrasound-guided biopsy of the mass suggested a poorly differentiated hepatocellular carcinoma. There was no disease elsewhere on PET scan. Surgical resection of the mass was performed. Pathological assessment suggested the tumor to be arising from the liver with invasion of the liver, abdominal wall musculature, and the adventitial surface of the ascending colon. A final diagnosis of localized biphasic malignant peritoneal mesothelioma with rhabdoid features was rendered based on morphology and the result of immunohistochemical studies. The abdominal wall margin was positive. The patient progressed over the course of 6 months despite receiving adjuvant chemotherapy and immunotherapy with metastases and a decline in performance status and was transitioned to hospice.

CONCLUSION: Localized malignant peritoneal mesotheliomas are rare tumors that may present clinically as a liver mass and simulate primary hepatic or secondary tumors. Definitive diagnosis is obtained by surgical resection in most cases. The clinical outcome is variable with most cases having a poor outcome.}, } @article {pmid31442913, year = {2019}, author = {Li, Z and Jiang, L and Chew, SH and Hirayama, T and Sekido, Y and Toyokuni, S}, title = {Carbonic anhydrase 9 confers resistance to ferroptosis/apoptosis in malignant mesothelioma under hypoxia.}, journal = {Redox biology}, volume = {26}, number = {}, pages = {101297}, pmid = {31442913}, issn = {2213-2317}, mesh = {Antigens, Neoplasm/*genetics/*metabolism ; Apoptosis/*genetics ; Biomarkers ; Carbonic Anhydrase IX/*genetics/*metabolism ; Cell Line, Tumor ; Ferroptosis/*genetics ; Humans ; Hypoxia/*metabolism ; Lung Neoplasms/*genetics/*metabolism ; Mesothelioma/*genetics/*metabolism ; Mesothelioma, Malignant ; Mitochondria/genetics/metabolism ; Models, Biological ; Reactive Oxygen Species/metabolism ; }, abstract = {Hypoxia and acidity provide microenvironment for selection under evolutionary pressure and proliferation in cancer cells. Carbonic anhydrases (CAs) are a superfamily of metalloenzymes present in all life kingdoms, equilibrating the reactions among CO2, bicarbonate and H[+]. CA9, a membrane-associated α-CA, has been a drug target for various cancers. Whereas iron is essential not only for cancer cells but also for all the lives on earth, little is known on the association among hypoxia, iron metabolism, extracellular acidity and redox regulation. Malignant mesothelioma (MM), an aggressive tumor with poor prognosis, is an intriguing model in that asbestos-associated pathogenesis includes excess iron environment during carcinogenesis. Re-analysis of rat asbestos-induced MM model revealed an inverse association between high CA9 expression and survival. Here we used human MMs to identify the molecular events surrounding CA9 from the viewpoint of iron metabolism. CA9 expression was significantly higher in MM cells than in MeT-5A mesothelial cells, which was further amplified under hypoxia (1%O2) with increased catalytic Fe(II). CA9 suppression by inhibitors (S4 and U104) decreased viability and migration of MM cells, accompanied by overexpression of TFRC, IREB1/2 and FPN1(SLC40A1) and by downregulation of FTH/FTL. This expressional pattern was similar to that of erastin-induced ferroptosis in the same cells. Furthermore, we observed mitochondrial fission and enhanced autophagy with increased catalytic Fe(II) in both mitochondria and lysosomes after CA9 inhibition, accompanied by increased peroxides, mitochondrial O2[-] and lipid peroxidation. The eventual cell death was significantly inhibited by deferoxamine, ferrostatin-1 and Z-VAD-FMK, suggesting a mixed cell death of ferroptosis and apoptosis. Therefore, CA9 plays a role in equilibrating among hypoxia, iron metabolism and redox regulation in MM cells.}, } @article {pmid31428834, year = {2019}, author = {Keshava, HB and Tang, A and Siddiqui, HU and Raja, S and Raymond, DP and Bribriesco, A and Stevenson, J and Murthy, SC and Ahmad, U}, title = {Largely Unchanged Annual Incidence and Overall Survival of Pleural Mesothelioma in the USA.}, journal = {World journal of surgery}, volume = {43}, number = {12}, pages = {3239-3247}, pmid = {31428834}, issn = {1432-2323}, support = {U01 HL088955/HL/NHLBI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Incidence ; Lung Neoplasms/*epidemiology/mortality ; Male ; Mesothelioma/*epidemiology/mortality ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/*epidemiology/mortality ; United States/epidemiology ; Young Adult ; }, abstract = {BACKGROUND: Projections based on regulations curtailing asbestos use in the USA suggest that peak incidence of pleural mesothelioma would occur between 2000 and 2005 and then decline. We analyzed the National Cancer Database (NCDB) to assess current trends in disease incidence, patient demographics, cancer treatment, and survival.

METHODS: The NCDB was queried to identify patients diagnosed with pleural mesothelioma from 2004 through 2014. Clinical and pathologic characteristics, treatments, and survival were analyzed. Risk factors for death were identified by multivariable Cox regression.

RESULTS: A total of 20,988 patients with pleural mesothelioma were reported to the NCDB. The number of cases per year increased from 1783 to 1961, accounting for roughly 0.3% of all reported cancers each year. The proportion of elderly patients increased from 75 to 80%, but distribution by sex remained constant (20% female). The proportion of patients undergoing treatment increased from 34 to 54%. One-year survival increased from 37 to 47% and 3-year survival from 9 to 15% (p < 0.001). Factors associated with improved survival included younger age, female sex, epithelioid histology, treatment in an academic center, health insurance, higher income, and multimodality therapy.

CONCLUSIONS: The annual incidence of mesothelioma has not declined this century and remains stable. Reporting of histologic and clinical staging has improved. National trends suggest that survival is slowly increasing despite an aging cohort. Multimodal therapy and treatment at academic centers are modifiable risk factors associated with improved survival.}, } @article {pmid31428586, year = {2019}, author = {Hoffmann, PR and Hoffmann, FW and Premeaux, TA and Fujita, T and Soprana, E and Panigada, M and Chew, GM and Richard, G and Hindocha, P and Menor, M and Khadka, VS and Deng, Y and Moise, L and Ndhlovu, LC and Siccardi, A and Weinberg, AD and De Groot, AS and Bertino, P}, title = {Multi-antigen Vaccination With Simultaneous Engagement of the OX40 Receptor Delays Malignant Mesothelioma Growth and Increases Survival in Animal Models.}, journal = {Frontiers in oncology}, volume = {9}, number = {}, pages = {720}, pmid = {31428586}, issn = {2234-943X}, support = {G12 MD007601/MD/NIMHD NIH HHS/United States ; R01 AI089999/AI/NIAID NIH HHS/United States ; P20 GM103466/GM/NIGMS NIH HHS/United States ; U54 MD007601/MD/NIMHD NIH HHS/United States ; R13 CA150300/CA/NCI NIH HHS/United States ; P30 GM114737/GM/NIGMS NIH HHS/United States ; U54 MD007584/MD/NIMHD NIH HHS/United States ; P30 GM103341/GM/NIGMS NIH HHS/United States ; G12 RR003061/RR/NCRR NIH HHS/United States ; P30 CA071789/CA/NCI NIH HHS/United States ; }, abstract = {Malignant Mesothelioma (MM) is a rare and highly aggressive cancer that develops from mesothelial cells lining the pleura and other internal cavities, and is often associated with asbestos exposure. To date, no effective treatments have been made available for this pathology. Herein, we propose a novel immunotherapeutic approach based on a unique vaccine targeting a series of antigens that we found expressed in different MM tumors, but largely undetectable in normal tissues. This vaccine, that we term p-Tvax, is comprised of a series of immunogenic peptides presented by both MHC-I and -II to generate robust immune responses. The peptides were designed using in silico algorithms that discriminate between highly immunogenic T cell epitopes and other harmful epitopes, such as suppressive regulatory T cell epitopes and autoimmune epitopes. Vaccination of mice with p-Tvax led to antigen-specific immune responses that involved both CD8[+] and CD4[+] T cells, which exhibited cytolytic activity against MM cells in vitro. In mice carrying MM tumors, p-Tvax increased tumor infiltration of CD4[+] T cells. Moreover, combining p-Tvax with an OX40 agonist led to decreased tumor growth and increased survival. Mice treated with this combination immunotherapy displayed higher numbers of tumor-infiltrating CD8[+] and CD4[+] T cells and reduced T regulatory cells in tumors. Collectively, these data suggest that the combination of p-Tvax with an OX40 agonist could be an effective strategy for MM treatment.}, } @article {pmid31420427, year = {2019}, author = {Bousema, JE and van de Luijtgaarden, KM and Wilhelmus, S and Poelman, MM}, title = {Acute severe abdominal pain in a young woman caused by a well-differentiated papillary mesothelioma of the peritoneum.}, journal = {BMJ case reports}, volume = {12}, number = {8}, pages = {}, pmid = {31420427}, issn = {1757-790X}, mesh = {Abdominal Pain/*diagnosis/etiology ; Acute Pain/*diagnosis/etiology ; Adult ; Female ; Humans ; Mesothelioma/complications/*diagnosis ; Peritoneal Neoplasms/complications/*diagnosis ; }, abstract = {Acute abdominal pain is a common symptom in young women. We describe a patient with acute illness and severe lower abdominal pain. Laboratory tests were normal except for mildly deranged inflammatory markers. No abnormalities were reported on abdominal ultrasonography and MRI, whereas diagnostic laparoscopy revealed a tumour located dorsally from the uterus. We resected the tumour and pathology results showed a well-differentiated papillary mesothelioma of the peritoneum (WDPMP). Microscopy showed evidence of acute ischaemia in the resected lesion, which was likely the cause of the acute abdominal pain. WDPMP is a rare disease that arises from the serous membranes which does not seem to have a relation to asbestos exposure. Generally, WDPMP has a mild clinical course and good long-term prognosis.}, } @article {pmid31419715, year = {2019}, author = {Consonni, D and Migliore, E and Barone-Adesi, F and Dallari, B and De Matteis, S and Oddone, E and Pesatori, AC and Riboldi, L and Mirabelli, D and Mensi, C}, title = {Gender differences in pleural mesothelioma occurrence in Lombardy and Piedmont, Italy.}, journal = {Environmental research}, volume = {177}, number = {}, pages = {108636}, doi = {10.1016/j.envres.2019.108636}, pmid = {31419715}, issn = {1096-0953}, mesh = {*Asbestos ; Female ; Humans ; Incidence ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Occupational Exposure/*statistics & numerical data ; Pleural Neoplasms/*epidemiology ; Registries ; Sex Factors ; }, abstract = {BACKGROUND: Higher mesothelioma rates in men (vs women) reflect more frequent and more intense asbestos exposure. We assessed the impact of exposure difference between genders on age-specific rates of pleural mesothelioma (PM) occurrence using data from two Italian regions.

METHODS: We used data from the Lombardy and Piedmont mesothelioma registries (period 2000-2016, age 45-74 years) to compare rates of PM in men and women and to estimate the rate advancement period (RAP).

RESULTS: Based on 3384 cases (2405 men, 979 women) in Lombardy and 2042 (1389 men, 653 women) in Piedmont, the rate ratio was 2.81 (90% confidence interval: 2.61-3.03) in Lombardy and 2.39 (2.17-2.62) in Piedmont. In both regions RAP ranged from 7 to 10 years (at age 45 and 63 in men, respectively).

CONCLUSION: Men showed more than twofold increased PM rates and reached the same incidence as women 7-10 years earlier. RAP can be a useful measure of exposure impact on premature disease occurrence.}, } @article {pmid31416570, year = {2019}, author = {Betti, M and Aspesi, A and Sculco, M and Matullo, G and Magnani, C and Dianzani, I}, title = {Genetic predisposition for malignant mesothelioma: A concise review.}, journal = {Mutation research. Reviews in mutation research}, volume = {781}, number = {}, pages = {1-10}, doi = {10.1016/j.mrrev.2019.03.001}, pmid = {31416570}, issn = {1388-2139}, mesh = {Animals ; Asbestos/toxicity ; DNA Repair/drug effects/genetics ; Environmental Exposure/adverse effects ; Genetic Predisposition to Disease/*genetics ; Germ-Line Mutation/drug effects/genetics ; Humans ; Lung Neoplasms/chemically induced/*etiology ; Mesothelioma/chemically induced/*etiology ; Mesothelioma, Malignant ; Risk Factors ; }, abstract = {Malignant mesothelioma (MM) is an aggressive cancer associated with asbestos exposure. Studies of familial malignant pleural mesothelioma (MPM) have suggested the existence of a genetic predisposition. Information on the role of genetic risk factors in the development of MM has been growing in the last years, and both low- and high-risk genetic factors have been identified, but genetic factors alone (without any exposure to asbestos or other mineral fibers) have never been shown to induce MM. Low-risk genetic factors have been identified in studies that systematically analyzed the whole genome. When considered alone these low-risk genetic factors carry a relative risk of MPM that is 10- to 15-fold lower than that carried by asbestos exposure; however, a large number of these factors in combination may increase the impact of asbestos exposure. High-risk genetic factors include truncating variants in the tumor suppressor BAP1 and in other tumor suppressor genes belonging to DNA repair pathways. Heterozygous germline variants in these genes may favor carcinogenesis if a second somatic variant occurs that impairs the wild-type allele. This impairment can cause genetic instability due to the suppression of a specific DNA repair pathway, and transformation. This genetic predisposition may have translational consequences, as it may predict patient response to drugs that induce tumor-specific synthetic lethality.}, } @article {pmid31413184, year = {2019}, author = {Barone-Adesi, F and Ferrante, D and Chellini, E and Merler, E and Pavone, V and Silvestri, S and Miligi, L and Gorini, G and Bressan, V and Girardi, P and Ancona, L and Romeo, E and Luberto, F and Sala, O and Scarnato, C and Menegozzo, S and Oddone, E and Tunesi, S and Perticaroli, P and Pettinari, A and Cuccaro, F and Curti, S and Baldassarre, A and Cena, T and Angelini, A and Marinaccio, A and Mirabelli, D and Musti, M and Pirastu, R and Ranucci, A and Magnani, C and , }, title = {Role of asbestos clearance in explaining long-term risk of pleural and peritoneal cancer: a pooled analysis of cohort studies.}, journal = {Occupational and environmental medicine}, volume = {76}, number = {9}, pages = {611-616}, doi = {10.1136/oemed-2019-105779}, pmid = {31413184}, issn = {1470-7926}, mesh = {Adolescent ; Adult ; Asbestos/*adverse effects ; Female ; Humans ; Italy/epidemiology ; Male ; Middle Aged ; Models, Theoretical ; Occupational Diseases/*mortality ; Occupational Exposure/*adverse effects ; Peritoneal Neoplasms/*mortality ; Pleural Neoplasms/*mortality ; Time Factors ; Young Adult ; }, abstract = {OBJECTIVES: Models based on the multistage theory of cancer predict that rates of malignant mesothelioma continuously increase with time since first exposure (TSFE) to asbestos, even after the end of external exposure. However, recent epidemiological studies suggest that mesothelioma rates level off many years after first exposure to asbestos. A gradual clearance of asbestos from the lungs has been suggested as a possible explanation for this phenomenon. We analysed long-term trends of pleural and peritoneal cancer mortality in subjects exposed to asbestos to evaluate whether such trends were consistent with the clearance hypothesis.

METHODS: We used data from a pool of 43 Italian asbestos cohorts (51 801 subjects). The role of asbestos clearance was explored using the traditional mesothelioma multistage model, generalised to include a term representing elimination of fibres over time.

RESULTS: Rates of pleural cancer increased until 40 years of TSFE, but remained stable thereafter. On the other hand, we observed a monotonic increase of peritoneal cancer with TSFE. The model taking into account asbestos clearance fitted the data better than the traditional one for pleural (p=0.004) but not for peritoneal (p=0.09) cancer.

CONCLUSIONS: Rates of pleural cancer do not increase indefinitely after the exposure to asbestos, but eventually reach a plateau. This trend is well described by a model accounting for a gradual elimination of the asbestos fibres. These results are relevant for the prediction of future rates of mesothelioma and in asbestos litigations.}, } @article {pmid31411568, year = {2019}, author = {Gudmundsson, G and Tomasson, K}, title = {[Asbestos and its effects on health of Icelanders - review].}, journal = {Laeknabladid}, volume = {105}, number = {7}, pages = {327-334}, doi = {10.17992/lbl.2019.0708.241}, pmid = {31411568}, issn = {1670-4959}, mesh = {Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Asbestosis/diagnostic imaging/*epidemiology/pathology ; Construction Materials/*adverse effects ; Environmental Exposure/*adverse effects ; Female ; Humans ; Iceland/epidemiology ; Incidence ; Lung Neoplasms/diagnostic imaging/*epidemiology/pathology ; Male ; Mesothelioma/diagnosis/*epidemiology ; Middle Aged ; Risk Assessment ; Risk Factors ; Sex Distribution ; Time Factors ; }, abstract = {Asbestos are crystallized silicate minerals that form fibers with different structures and characteristics. Asbestos fibers are very durable and can tolerate very high temperatures. Therefore it was common to use asbestos as a fire retardants, heat insulation and where high temperature is used. Asbestos has been banned in Iceland from 1983 but can still be found in large amounts in buildings, ships and hot water pipes. Large amounts of asbestos were imported in the years before the ban but diminished soon to almost nothing today. Needle or filamentous shaped dust is released when working with asbestos. It is this dust that is dangerous for health. The latent time from exposure to disease can be up to forty years. Asbestos reaches the lungs via inhalation and can cause asbestosis that is a form of lung fibrosis with slow progression. Asbestos can also cause benign pleural effusions, pleural plaques and diffuse pleural thickening. Asbestos is a carcinogen. Lung cancer is most common but asbestos is also a risk factor for cancers of other organs. Mesothelioma is most common in the pleura but can be seen in other membranes. The incidence of these tumors is high in Iceland and is still increasing among males. Of all the European countries mortality is highest in Iceland. It is important for physicians to include asbestos exposure in the differential diagnosis of lung diseases and when lung cancer is diagnosed.}, } @article {pmid31411522, year = {2019}, author = {Jiang, Y and Mei, Z and Cao, H and Li, S and Xu, H and Qiu, H and Liu, Y}, title = {Meningeal metastasis of a malignant peritoneal mesothelioma: A case report and literature review.}, journal = {Cancer biology & therapy}, volume = {20}, number = {12}, pages = {1409-1415}, pmid = {31411522}, issn = {1555-8576}, mesh = {Asbestos/adverse effects ; Biomarkers, Tumor ; Biopsy ; Disease Progression ; Fatal Outcome ; Female ; Genetic Testing ; Humans ; Immunohistochemistry ; Lung Neoplasms/diagnostic imaging/etiology/*pathology ; Meningeal Neoplasms/*diagnosis/*secondary/therapy ; Mesothelioma/diagnostic imaging/etiology/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Multimodal Imaging/methods ; Occupational Exposure/adverse effects ; Peritoneal Neoplasms/diagnostic imaging/etiology/*pathology ; Radiotherapy, Intensity-Modulated ; }, abstract = {Malignant peritoneal mesothelioma is a very rare tumor originating from the peritoneal serous mesothelium. Meningeal metastasis of malignant peritoneal is even more rare. Here, we reported a case of a 60-year-old female patient with a history of exposure to asbestos for 10 years who presented with massive peritoneal effusion followed by disorder of consciousness and symptoms of cranial nerve injury. The patient was diagnosed as peritoneal mesothelioma with meningeal metastasis through neurological symptoms, cytological finding of cerebrospinal fluid combined with cranial magnetic resonance imaging (MRI). The patient received systemic chemotherapy and total craniospinal irradiation. The follow up visits showed that the survival time of patient after diagnosis of meningeal metastasis from peritoneal mesothelioma was 5 months. To our knowledge, this is the first case of menigeal metastasis of peritoneal mesothelioma. We hope this particular case may be helpful in providing some experience to the treatment of peritoneal mesothelioma with meningeal metastasis.}, } @article {pmid31406977, year = {2019}, author = {Boffetta, P and Righi, L and Ciocan, C and Pelucchi, C and La Vecchia, C and Romano, C and Papotti, M and Pira, E}, title = {Validation of the diagnosis of mesothelioma and BAP1 protein expression in a cohort of asbestos textile workers from Northern Italy.}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {30}, number = {11}, pages = {1844}, doi = {10.1093/annonc/mdz217}, pmid = {31406977}, issn = {1569-8041}, } @article {pmid31406207, year = {2019}, author = {Munson, PB and Hall, EM and Farina, NH and Pass, HI and Shukla, A}, title = {Exosomal miR-16-5p as a target for malignant mesothelioma.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {11688}, pmid = {31406207}, issn = {2045-2322}, support = {R01 ES021110/ES/NIEHS NIH HHS/United States ; R21 ES028857/ES/NIEHS NIH HHS/United States ; S10 OD025030/OD/NIH HHS/United States ; }, mesh = {Aniline Compounds/pharmacology ; Antineoplastic Agents/*pharmacology ; Benzylidene Compounds/pharmacology ; Cell Death ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cyclin D1/*genetics/metabolism ; Exosomes/*chemistry/metabolism ; *Gene Expression Regulation, Neoplastic ; Humans ; Indoles/pharmacology ; Lung Neoplasms/genetics/metabolism/pathology ; Maleimides/pharmacology ; Mesothelioma/genetics/metabolism/pathology ; Mesothelioma, Malignant ; MicroRNAs/*genetics/metabolism ; Molecular Targeted Therapy/methods ; Ornithine/analogs & derivatives/pharmacology ; Proto-Oncogene Proteins c-bcl-2/*genetics/metabolism ; Signal Transduction ; Small Molecule Libraries/pharmacology ; Transfection ; }, abstract = {Malignant mesothelioma (MM) is an asbestos-induced cancer arising on the mesothelial surface of organ cavities. MM is essentially incurable without a means of early diagnosis and no successful standard of care. These facts indicate a deep chasm of knowledge that needs to be filled. Our group recently delved into MM tumor biology from the perspective of exosome-contained microRNAs (miRNAs). We discovered that the most abundant miRNAs in MM cancer exosomes were tumor suppressors, particularly miR-16-5p. This observation lead us to hypothesize that MM cells preferentially secreted tumor-suppressor miRNAs via exosomes. Through separate avenues of potential therapeutic advance, we embarked on an innovative strategy to kill MM tumor cells. We employed small molecule inhibitors to block exosome secretion, thereby reducing miR-16-5p exosome loss and replenishing cellular miR-16-5p leading to reduced tumorigenic capacity and miR-16-5p target oncoproteins CCND1 and BCL2. Additionally, we force-fed MM tumor exosomes back to MM tumor cells, which led to cell death, and a reduction in the same oncoproteins. We recapitulated these results with direct transfection of miR-16-5p, confirmed that this is a cancer-cell specific effect, and elucidated a part of the miR-16-5p mechanism of exosome loading.}, } @article {pmid31391078, year = {2019}, author = {Luberto, F and Ferrante, D and Silvestri, S and Angelini, A and Cuccaro, F and Nannavecchia, AM and Oddone, E and Vicentini, M and Barone-Adesi, F and Cena, T and Mirabelli, D and Mangone, L and Roncaglia, F and Sala, O and Menegozzo, S and Pirastu, R and Azzolina, D and Tunesi, S and Chellini, E and Miligi, L and Perticaroli, P and Pettinari, A and Bressan, V and Merler, E and Girardi, P and Bisceglia, L and Marinaccio, A and Massari, S and Magnani, C and , }, title = {Cumulative asbestos exposure and mortality from asbestos related diseases in a pooled analysis of 21 asbestos cement cohorts in Italy.}, journal = {Environmental health : a global access science source}, volume = {18}, number = {1}, pages = {71}, pmid = {31391078}, issn = {1476-069X}, support = {Current research 2012: asbestos project. Operative Unit 2//Istituto Superiore Sanità/International ; Piano Ricerca 2016-2018, "Programma Speciale Amianto", Ricerca BRIC id 55//INAIL/International ; Piano Ricerca 2016-2018, "Programma Speciale Amianto", Ricerca BRIC id 59//INAIL/International ; }, mesh = {Adult ; Asbestos/*adverse effects ; Asbestosis/*epidemiology/etiology ; Cohort Studies ; Female ; Humans ; Italy/epidemiology ; Male ; Middle Aged ; Neoplasms/chemically induced/*epidemiology ; Occupational Exposure/*adverse effects ; Sex Factors ; Time Factors ; Young Adult ; }, abstract = {BACKGROUND: Despite the available information on cancer risk, asbestos is used in large areas in the world, mostly in the production of asbestos cement. Moreover, questions are raised regarding the shape of the dose response relation, the relation with time since exposure and the association with neoplasms in various organs. We conducted a study on the relationship between cumulative asbestos exposure and mortality from asbestos related diseases in a large Italian pool of 21 cohorts of asbestos-cement workers with protracted exposure to both chrysotile and amphibole asbestos.

METHODS: The cohort included 13,076 workers, 81.9% men and 18.1% women, working in 21 Italian asbestos-cement factories, with over 40 years of observation. Exposure was estimated by plant and period, and weighted for the type of asbestos used. Data were analysed with consideration of cause of death, cumulative exposure and time since first exposure (TSFE), and by gender. SMRs were computed using reference rates by region, gender and calendar time. Poisson regression models including cubic splines were used to analyse the effect of cumulative exposure to asbestos and TSFE on mortality for asbestos-related diseases. 95% Confidence Intervals (CI) were computed according to the Poisson distribution.

RESULTS: Mortality was significantly increased for 'All Causes' and 'All Malignant Neoplasm (MN)', in both genders. Considering asbestos related diseases (ARDs), statistically significant excesses were observed for MN of peritoneum (SMR: men 14.19; women 15.14), pleura (SMR: 22.35 and 48.10), lung (SMR: 1.67 and 1.67), ovary (in the highest exposure class SMR 2.45), and asbestosis (SMR: 507 and 1023). Mortality for ARDs, in particular pleural and peritoneal malignancies, lung cancer, ovarian cancer and asbestosis increased monotonically with cumulative exposure. Pleural MN mortality increased progressively in the first 40 years of TSFE, then reached a plateau, while peritoneal MN showed a continuous increase. The trend of lung cancer SMRs also showed a flattening after 40 years of TSFE. Attributable proportions for pleural, peritoneal, and lung MN were respectively 96, 93 and 40%.

CONCLUSIONS: Mortality for ARDs was associated with cumulative exposure to asbestos. Risk of death from pleural MN did not increase indefinitely with TSFE but eventually reached a plateau, consistently with reports from other recent studies.}, } @article {pmid31388672, year = {2020}, author = {Corti, A and Bonetti, J and Dominici, S and Piaggi, S and Fierabracci, V and Foddis, R and Pompella, A}, title = {Induction of Gamma-Glutamyltransferase Activity and Consequent Pro-oxidant Reactions in Human Macrophages Exposed to Crocidolite Asbestos.}, journal = {Toxicological sciences : an official journal of the Society of Toxicology}, volume = {177}, number = {2}, pages = {476-482}, doi = {10.1093/toxsci/kfz175}, pmid = {31388672}, issn = {1096-0929}, mesh = {*Asbestos ; *Asbestos, Crocidolite/toxicity ; Humans ; Macrophages ; Reactive Oxygen Species ; gamma-Glutamyltransferase ; }, abstract = {Asbestos is the main causative agent of malignant pleural mesothelioma. The variety known as crocidolite (blue asbestos) owns the highest pathogenic potential, due to the dimensions of its fibers as well as to its content of iron. The latter can in fact react with macrophage-derived hydrogen peroxide in the so called Fenton reaction, giving rise to highly reactive and mutagenic hydroxyl radical. On the other hand, hydroxyl radical can as well originate after thiol-dependent reduction of iron, a process capable of starting its redox cycling. Previous studies showed that glutathione (GSH) is one such thiol, and that cellular gamma-glutamyltransferase (GGT) can efficiently potentiate GSH-dependent iron redox cycling and consequent oxidative stress. As GGT is expressed in macrophages and is released upon their activation, the present study was aimed at verifying the hypothesis that GSH/GGT-dependent redox reactions may participate in the oxidative stress following the activation of macrophages induced by crocidolite asbestos. Experiments in acellular systems confirmed that GGT-mediated metabolism of GSH can potentiate crocidolite-dependent production of superoxide anion, through the production of highly reactive dipeptide thiol cysteinyl-glycine. Cultured THP-1 macrophagic cells, as well as isolated monocytes obtained from healthy donors and differentiated to macrophages in vitro, were investigated as to their expression of GGT and the effects of exposure to crocidolite. The results show that crocidolite asbestos at subtoxic concentrations (50-250 ng/1000 cells) can upregulate GGT expression, which raises the possibility that macrophage-initiated, GSH/GGT-dependent pro-oxidant reactions may participate in the pathogenesis of tissue damage and inflammation consequent to crocidolite intoxication.}, } @article {pmid31383968, year = {2020}, author = {Wronkiewicz, SK and Roggli, VL and Hinrichs, BH and Kendler, A and Butler, RA and Christensen, BC and Marsit, CJ and Nelson, HH and McClean, MD and Kelsey, KT and Langevin, SM}, title = {Chrysotile fibers in tissue adjacent to laryngeal squamous cell carcinoma in cases with a history of occupational asbestos exposure.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {33}, number = {2}, pages = {228-234}, pmid = {31383968}, issn = {1530-0285}, support = {R21 DE027227/DE/NIDCR NIH HHS/United States ; P30 ES006096/ES/NIEHS NIH HHS/United States ; R01 CA100679/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Asbestos, Serpentine/*adverse effects/analysis ; Case-Control Studies ; Epithelial Cells/chemistry/ultrastructure ; Humans ; Laryngeal Neoplasms/chemistry/*etiology/ultrastructure ; Larynx/chemistry/ultrastructure ; Male ; Middle Aged ; Mineral Fibers/adverse effects/analysis ; Occupational Exposure/*adverse effects ; Risk Assessment ; Risk Factors ; Squamous Cell Carcinoma of Head and Neck/chemistry/*etiology/ultrastructure ; }, abstract = {Asbestos describes a group of naturally occurring fibrous silicate mineral compounds that have been associated with a number of respiratory maladies, including mesothelioma and lung cancer. In addition, based primarily on epidemiologic studies, asbestos has been implicated as a risk factor for laryngeal and pharyngeal squamous cell carcinoma (SCC). The main objective of this work was to strengthen existing evidence via empirical demonstration of persistent asbestos fibers embedded in the tissue surrounding laryngeal and pharyngeal SCC, thus providing a more definitive biological link between exposure and disease. Six human papillomavirus (HPV)-negative laryngeal (n = 4) and pharyngeal (n = 2) SCC cases with a history working in an asbestos-exposed occupation were selected from a large population-based case-control study of head and neck cancer. A laryngeal SCC case with no history of occupational asbestos exposure was included as a control. Tissue cores were obtained from adjacent nonneoplastic tissue in tumor blocks from the initial primary tumor resection, and mineral fiber analysis was performed using a scanning electron microscope equipped with an energy dispersive X-ray analyzer (EDXA). Chrysotile asbestos fiber bundles were identified in 3/6 of evaluated cases with a history of occupational asbestos exposure. All three cases had tumors originating in the larynx. In addition, a wollastonite fiber of unclear significance was identified one of the HPV-negative pharyngeal SCC cases. No mineral fibers were identified in adjacent tissue of the case without occupational exposure. The presence of asbestos fibers in the epithelial tissue surrounding laryngeal SCC in cases with a history of occupational asbestos exposure adds a key line of physical evidence implicating asbestos as an etiologic factor.}, } @article {pmid31380709, year = {2019}, author = {Jacobs, NFB and Towle, KM and Finley, BL and Gaffney, SH}, title = {An updated evaluation of potential health hazards associated with exposures to asbestos-containing drywall accessory products.}, journal = {Critical reviews in toxicology}, volume = {49}, number = {5}, pages = {430-444}, doi = {10.1080/10408444.2019.1639612}, pmid = {31380709}, issn = {1547-6898}, mesh = {*Asbestos ; Asbestos, Amphibole ; Asbestos, Serpentine ; *Construction Materials ; Environmental Exposure/*analysis/standards/statistics & numerical data ; Humans ; Lung Neoplasms/epidemiology ; No-Observed-Adverse-Effect Level ; Risk Assessment ; }, abstract = {Following a previously published (2012) evaluation of the potential health hazards related to the use of asbestos-containing drywall accessory products, additional information regarding asbestos exposures during the use of accessory products, as well as studies of chrysotile asbestos risk as a function of exposure, have been published in the peer-reviewed literature. The purpose of this analysis is to update the original evaluation with this new information. It was previously estimated that a professional drywaller performing joint compound-associated tasks could have a lifetime cumulative chrysotile exposure of 12-26 f/cc-year. Using conservative assumptions regarding airborne asbestos levels during different drywalling tasks, task duration, and job tenure, we found that a range of 4.3-36.3 f/cc-year is a plausible estimate of a career drywaller's cumulative asbestos exposure from historical joint compound use. The estimated range for bystander exposures would be below (sometimes significantly below) this range depending on the frequency and duration of work near drywallers. Further, the estimated drywaller and bystander total fiber exposures were well below a recently published "no-observed adverse effect level, best estimate" for predominately chrysotile exposures of 89-168 f/cc-year for lung cancer and 208-415 f/cc-year for mesothelioma. We also determined that, even if the chrysotile or possibly talc ingredients in the drywall products had contained asbestiform tremolite, the cumulative tremolite exposures would have been well below a recently published tremolite no-effect level of 0.5-2.6 f/cc-year. Based on our calculations, typical drywall work using asbestos-containing drywall accessory products is not expected to increase the risk of asbestos-related lung cancer or mesothelioma. These conclusions are consistent with the lack of epidemiological evidence that drywall work resulted in an increased incidence of asbestos-related disease in the drywall trades.}, } @article {pmid31380702, year = {2019}, author = {Marsh, GM and Ierardi, AM and Benson, SM and Finley, BL}, title = {Occupational exposures to cosmetic talc and risk of mesothelioma: an updated pooled cohort and statistical power analysis with consideration of latency period.}, journal = {Inhalation toxicology}, volume = {31}, number = {6}, pages = {213-223}, doi = {10.1080/08958378.2019.1645768}, pmid = {31380702}, issn = {1091-7691}, mesh = {Adult ; Air Pollutants, Occupational/*adverse effects ; Cohort Studies ; Europe/epidemiology ; Humans ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*epidemiology ; Talc/*adverse effects ; Young Adult ; }, abstract = {Objectives: We previously published a pooled statistical power analysis of mesothelioma incidence in the Italian, Norwegian, Austrian, and French cosmetic talc miner and miller cohorts. Soon thereafter, updates to the Italian and Norwegian cohorts were published, providing an additional 14,322 person-years of observation. In this study, we provide an updated power analysis using the newly available information. Methods: We pooled the current results regarding pleural cancer/mesothelioma mortality or incidence in four cosmetic talc miner and miller cohorts in Italy, Norway, Austria, and France. We used the expected numbers of cases as reported by the authors and the power analysis was based on an a priori one-sided significance level of 0.05 and Poisson distribution probabilities. Results: There was a pooled total of 113,344 person-years in the cohorts. Although 3.0 pleural cancers/mesotheliomas were expected, there were no reported pleural cancer or mesothelioma cases in any cohort. Our pooled analysis was associated with 79 and 62% power to detect a 3.0-fold and 2.5-fold or greater increase in pleural cancer/mesothelioma, respectively. These favorable power characteristics were effectively maintained when restricting the pooled cohort to workers with a latency period of 30 or more years (observation time from first employment). Conclusions: The epidemiological evidence from the cosmetic talc miner/miller cohort studies does not support the hypothesis that exposure to cosmetic talc is associated with the development of pleural cancer/mesothelioma.}, } @article {pmid31376434, year = {2019}, author = {Butnor, KJ and Pavlisko, EN and Sporn, TA and Roggli, VL}, title = {Mesothelioma of the tunica vaginalis testis.}, journal = {Human pathology}, volume = {92}, number = {}, pages = {48-58}, doi = {10.1016/j.humpath.2019.07.009}, pmid = {31376434}, issn = {1532-8392}, mesh = {Adult ; Aged ; Aged, 80 and over ; Humans ; Lung Neoplasms/*pathology/surgery ; Male ; Mesothelioma/*pathology/surgery ; Mesothelioma, Malignant ; Middle Aged ; Orchiectomy ; Retrospective Studies ; Testicular Neoplasms/*pathology/surgery ; Testis/*pathology/surgery ; Treatment Outcome ; }, abstract = {Malignant mesothelioma (MM) arising from the serosal membranes of the tunica vaginalis testis (TVT) is rare. Most examples in the published medical literature are individual case reports. This study presents the clinicopathological findings of mesothelioma of the TVT in one of the largest series to date. Individuals with mesothelioma of the TVT were identified from a database of more than 4000 mesothelioma cases, and their clinicopathological features were recorded. Eighteen men with MM and 2 with well-differentiated papillary mesothelioma of the TVT were identified, which represented 0.6% of males with mesothelioma in study population. The median age at diagnosis was 72 years (range, 32-85 years). A neoplasm was not suspected preoperatively in 12 of the 17 (71%) men whose clinical presentation was known, 7 of whom presented with hydrocele and 5 with inguinal hernia. The other 5 had a clinically recognized mass. Seven of the men underwent herniorrhaphy; 7, radical orchiectomy; 3, hydrocelectomy; and 3, paratesticular mass biopsy or excision as the initial diagnostic procedure. Twelve of the MM cases were epithelioid and 6 were biphasic. Among the 6 men with MM who had ≥6 months of follow-up, 1 was alive with no evidence of disease at 6 months, and 5 were known to have died of disease 8-74 months (median = 31.5 months) following diagnosis. Three men with MM had received either chemotherapy or radiation therapy. Of the 2 men initially diagnosed with well-differentiated papillary mesothelioma, 1 was alive without evidence of disease 5 years after diagnosis, while the other had findings more compatible with MM with peritoneal involvement 2 years following initial diagnosis. In 15 of the 18 cases of MM (83%), there was documented occupational or paraoccupational exposure to asbestos, the average duration of which was 33 years (range, 2-46 years). Information regarding the presence or absence of pleural plaques was available in 5 of the MM cases, and pleural plaques had been found in 4. Lung tissue was not available for fiber analysis in any of the cases. One additional case originally diagnosed at another institution as MM of the TVT was reclassified as adenocarcinoma following performance of additional immunohistochemical testing. TVT is a rare site of MM, the diagnosis of which is often unsuspected preoperatively. Like its counterparts at other serosal sites, MM of the TVT is an aggressive tumor with a poor prognosis that evidence would suggest is etiologically associated with asbestos in at least some cases.}, } @article {pmid31375830, year = {2019}, author = {Sorahan, TM}, title = {Cancer incidence in UK electricity generation and transmission workers, 1973-2015.}, journal = {Occupational medicine (Oxford, England)}, volume = {69}, number = {5}, pages = {342-351}, pmid = {31375830}, issn = {1471-8405}, mesh = {Asbestos/adverse effects ; Female ; Humans ; Incidence ; Male ; Mesothelioma/epidemiology/etiology ; Neoplasms/*epidemiology/etiology ; Occupational Diseases/*epidemiology ; Occupational Exposure/adverse effects/statistics & numerical data ; *Power Plants ; United Kingdom/epidemiology ; }, abstract = {BACKGROUND: Long-term health outcomes in cohorts of workers from the electricity supply industry have been studied.

AIMS: The aim of the study was to examine updated cancer incidence findings among a cohort of UK electricity generation and transmission workers.

METHODS: Cancer morbidity experienced by 81 616 employees of the former Central Electricity Generating Board of England and Wales was investigated for the period 1973-2015. All employees had worked for at least 6 months with some employment between 1973 and 1982. Standardized registration ratios (SRRs) were calculated based on national rates.

RESULTS: Overall cancer morbidity was slightly below expectation in males. Significant excesses were found in male workers for mesothelioma (observed [Obs] 763, SRR 326), skin cancer (non-melanoma) (Obs 5616, SRR 106), and prostate cancer (Obs 4298, SRR 106), and in female workers for cancer of the small intestine (Obs 13, SRR 220), nasal cancer (Obs 11, SRR 407), and breast cancer (Obs 758, SRR 110). More detailed analyses showed important contrasts, particularly for mesothelioma, lung cancer, skin cancer, prostate cancer and breast cancer.

CONCLUSIONS: A clear occupational excess of mesothelioma was not matched by a corresponding excess of asbestos-induced lung cancer. Confident interpretation of the excesses of cancers of the nasal cavities and small intestine is not possible, although occupational exposures received in this industry may well not be involved. An excess of skin cancer in transmission workers may be associated with outdoor working.}, } @article {pmid31375770, year = {2020}, author = {Churg, A and Galateau-Salle, F and Roden, AC and Attanoos, R and von der Thusen, JH and Tsao, MS and Chang, N and De Perrot, M and Dacic, S}, title = {Malignant mesothelioma in situ: morphologic features and clinical outcome.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {33}, number = {2}, pages = {297-302}, pmid = {31375770}, issn = {1530-0285}, mesh = {Aged ; Biomarkers, Tumor/analysis/genetics ; Biopsy ; Cell Proliferation ; Cyclin-Dependent Kinase Inhibitor p16/genetics ; Disease Progression ; Female ; Humans ; Male ; Mesothelioma, Malignant/enzymology/genetics/*pathology/therapy ; Middle Aged ; Neoplasm Invasiveness ; Peritoneal Neoplasms/enzymology/genetics/*pathology/therapy ; Pleural Neoplasms/enzymology/genetics/*pathology/therapy ; Purine-Nucleoside Phosphorylase/analysis ; Time Factors ; Treatment Outcome ; Tumor Suppressor Proteins/genetics ; Ubiquitin Thiolesterase/genetics ; }, abstract = {The existence of an in situ phase of malignant mesothelioma has long been postulated but until recently has been impossible to prove. Here we describe ten patients with mesothelioma in situ, defined by a single layer of surface mesothelial cells showing loss of BAP1 nuclear immunostaining, no evidence of tumor by imaging and/or by direct examination of the pleura/peritoneum, and no invasive mesothelioma developing for at least 1 year. Nine cases were pleural and one peritoneal. Most patients were biopsied for repeated effusions of unknown etiology; in two patients mesothelioma in situ was found incidentally in lung cancer resections. In addition to surface mesothelium with BAP1 loss, one case had a surface papillary proliferation with BAP1 loss, and two cases had a small (few millimeter) nodule with BAP1 loss. CDKN2A was deleted by FISH in one of eight cases. Methylthioadenosine phosphorylase showed partial loss in the surface mesothelium by immunohistochemistry in three cases. Invasive malignant mesothelioma developed in seven patients with time between biopsy and invasive disease from 12 to 92 (median 60) months. Invasive mesothelioma has not developed in the other three patients at 12, 57, and 120 months, but the latter patient, who has pleural plaques, still has repeated pleural effusions, probably representing a so-called "benign asbestos effusion." We conclude that mesothelioma in situ, as diagnosed using the criteria outlined above, is associated with a high risk of developing invasive mesothelioma, but typically over a relatively protracted time, so that curable interventions maybe possible.}, } @article {pmid31372931, year = {2020}, author = {Itano, H and Takeda, T and Yamada, T and Koide, M and Kobayashi, T}, title = {Heterologous sarcomatoid pleural mesothelioma with osteosarcomatous differentiation: a report of autopsy case that accomplished trimodality therapy and review of the literature.}, journal = {General thoracic and cardiovascular surgery}, volume = {68}, number = {8}, pages = {871-879}, doi = {10.1007/s11748-019-01182-8}, pmid = {31372931}, issn = {1863-6713}, mesh = {Aged ; Asbestos/adverse effects ; Autopsy ; Biopsy ; Cell Differentiation ; Fatal Outcome ; Humans ; Lung/pathology ; Male ; Mesothelioma/chemically induced/diagnostic imaging/*surgery ; Mesothelioma, Malignant/*surgery ; Neoplasm Recurrence, Local/mortality/*surgery ; Osteosarcoma/*surgery ; Pericardium/surgery ; Pleura/diagnostic imaging/*pathology ; Pleural Neoplasms/diagnostic imaging/*surgery ; Pneumonectomy ; Thoracic Wall/pathology ; }, abstract = {Heterologous mesothelioma is a very rare subtype of sarcomatoid mesothelioma characterized by the presence of malignant heterologous elements. A 69-year-old man with a strong history of asbestos exposure presented with a 5-cm mass in his chest wall, destroying the right 5th rib and spreading along the parietal pleura, on a CT. Biopsy revealed heterologous mesothelioma with osteosarcomatous elements, following which left extrapleural pneumonectomy was performed with combined resection of pericardium, hemidiaphragm, and 4th, 5th, and 6th costal segments. A small cytokeratin-positive epithelioid component in the resected tumor definitively confirmed the diagnosis. Post-operative chemotherapy and intensity-modulated radiotherapy were undertaken. After 12-month disease-free period post treatment, rapid intraperitoneal recurrence resulted in death. Autopsy revealed no tumors in the left thorax. We present here a case of heterologous osteosarcomatous pleural mesothelioma that followed a unique clinical course after trimodality therapy. In addition, literature of 54 cases of the similar heterologous mesothelioma was reviewed.}, } @article {pmid31366157, year = {2019}, author = {Gogou, E and Hatzoglou, C and Zarogiannis, SG and Malli, F and Jagirdar, RM and Gourgoulianis, KI}, title = {Mesothelioma Mortality Rates in Greece for the Period 2005-2015 Is Increased Compared to Previous Decades.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {55}, number = {8}, pages = {}, pmid = {31366157}, issn = {1648-9144}, mesh = {Aged ; Aged, 80 and over ; Cause of Death/*trends ; Female ; Geographic Mapping ; Greece/epidemiology ; Humans ; Male ; Mesothelioma/epidemiology/*mortality ; Middle Aged ; Occupational Diseases/epidemiology/mortality ; }, abstract = {Background and Objective: To present summary statistics regarding malignant mesothelioma (MM) mortality in Greece during the period 2005-2015 and compare it with previous decades, along with gender, age and geographical area analysis. Materials and Methods: The Hellenic Statistical Authority provided the data, which included all deaths for the period 1983 to 2015 that mentioned MM as the death cause in the corresponding death certificate. MM mortality rates have been calculated with respect to gender, age, and geographical location in Greece. Furthermore, a comparison analysis was made among three eleven consecutive year periods, in order to assess potential changes in the mortality rates. Results: The MM mortality rate has significantly increased during the period 2005-2015 both in males and females compared to earlier decades. The maximum number of MM deaths has shifted to an older age group of 70-80 years during the 2005-2015 period as compared to that of 1983-2004 in both genders. Additionally, MM mortality rates have significantly increased in all geographical areas except for the Epirus Prefecture. Conclusions: Our results demonstrate an increased MM mortality rate in Greece for the decade 2005-2015 as compared to the two previous decades. This increase is possibly due to the fact that the peak in asbestos production and use in Greece was in mid 1990s, while the asbestos ban came in effect in 2005. Based on these findings the MM epidemic in Greece has not yet peaked, therefore it is important to implement screening strategies for early MM detection.}, } @article {pmid31364588, year = {2019}, author = {The Lancet Oncology, }, title = {Asbestos exposure: the dust cloud lingers.}, journal = {The Lancet. Oncology}, volume = {20}, number = {8}, pages = {1035}, doi = {10.1016/S1470-2045(19)30462-0}, pmid = {31364588}, issn = {1474-5488}, mesh = {Asbestos/*adverse effects ; Environmental Exposure/adverse effects ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Mesothelioma, Malignant ; Occupational Exposure/adverse effects ; }, } @article {pmid31360386, year = {2019}, author = {Borrelli, E and Babcock, Z and Kogut, S}, title = {Costs of medical care for mesothelioma.}, journal = {Rare tumors}, volume = {11}, number = {}, pages = {2036361319863498}, pmid = {31360386}, issn = {2036-3605}, abstract = {Malignant mesothelioma is a rare and devastating form of cancer with an increasing economic burden. We sought to describe the direct cost burden of mesothelioma to the US health system. A systematic literature review was performed to locate published estimates of the medical cost of mesothelioma. In addition, we performed an analysis of hospital discharge data from the National Inpatient Sample, Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality. We also reviewed publicly available legal settlements. We found that published estimates of the cost of medical care for mesothelioma are sparse, and differ with respect to nation, timeframe, and types of cost included. For the year 2014 in the United States, we estimated a mean cost per mesothelioma hospitalization of US$24,124 (95% confidence interval: US$20,819-US$28,983) and a total cost for hospital care of US$44,214,835. In conclusion, we found that reports describing the direct medical cost of care for mesothelioma in the United States are lacking, yet the per-patient cost of care is substantial, as evidenced by analyses of inpatient care and legal settlements.}, } @article {pmid31355511, year = {2019}, author = {Lee, MJ and Kuehne, N and Hueniken, K and Liang, S and Rai, S and Sorotsky, H and Herman, M and Shepshelovich, D and Bruce, J and Liang, M and Patel, D and Cheng, D and Chen, Z and Eng, L and Brown, MC and Cho, J and Leighl, NB and de Perrot, M and Reisman, D and Xu, W and Bradbury, PA and Liu, G}, title = {Association of two BRM promoter polymorphisms and smoking status with malignant pleural mesothelioma risk and prognosis.}, journal = {Molecular carcinogenesis}, volume = {58}, number = {11}, pages = {1960-1973}, doi = {10.1002/mc.23088}, pmid = {31355511}, issn = {1098-2744}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Lung Neoplasms/*genetics/pathology ; Male ; Mesothelioma/*genetics/pathology ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/*genetics/pathology ; Polymorphism, Single Nucleotide/genetics ; Prognosis ; Promoter Regions, Genetic ; Risk Factors ; Smoking/*adverse effects/genetics ; Transcription Factors/*genetics ; }, abstract = {Brahma (BRM), of the SWI/SNF complex, has two 6 to 7 bp insertion promoter polymorphisms (BRM-741/BRM-1321) that cause epigenetic BRM suppression, and are associated with risk of multiple cancers. BRM polymorphisms were genotyped in malignant pleural mesothelioma (MPM) cases and asbestos-exposed controls. Multivariable logistic regression (risk) and Cox regression (prognosis) were performed, including stratified analyses by smoking status to investigate the effect of polymorphisms on MPM risk and prognosis. Although there was no significant association overall between BRM-741/BRM-1321 and risk in patients with MPM, a differential effect by smoking status was observed (P-interaction < .001), where homozygous variants were protective (aOR of 0.18-0.28) in ever smokers, while never smokers had increased risk when carrying homozygous variants (aOR of 2.7-4.4). While there was no association between BRM polymorphisms and OS in ever-smokers, the aHR of carrying homozygous-variants of BRM-741, BRM-1321 or both were 4.0 to 8.6 in never-smokers when compared to wild-type carriers. Mechanistically, lower mRNA expression of BRM was associated with poorer general cancer prognosis. Electrophoretic mobility shift assays and chromatin immunoprecipitation experiments (ChIP) revealed high BRM insertion variant homology to MEF2 regulatory binding sites. ChIP experimentation confirmed MEF2 binding only occurs in the presence of insertion variants. DNA-affinity purification assays revealed YWHA scaffold proteins as vital to BRM mRNA expression. Never-smokers who carry BRM homozygous variants have an increased chance of developing MPM, which results in worse prognosis. In contrast, in ever-smokers, there may be a protective effect, with no difference in overall survival. Mechanisms for the interaction between BRM and smoking require further study.}, } @article {pmid31355131, year = {2019}, author = {Di Somma, S and Iannuzzi, CA and Passaro, C and Forte, IM and Iannone, R and Gigantino, V and Indovina, P and Botti, G and Giordano, A and Formisano, P and Portella, G and Malfitano, AM and Pentimalli, F}, title = {The Oncolytic Virus dl922-947 Triggers Immunogenic Cell Death in Mesothelioma and Reduces Xenograft Growth.}, journal = {Frontiers in oncology}, volume = {9}, number = {}, pages = {564}, pmid = {31355131}, issn = {2234-943X}, abstract = {Background: Malignant pleural mesothelioma (MPM) is an aggressive cancer associated with asbestos exposure that urgently requires effective therapeutic strategies. Current treatments are unable to increase significantly patient survival, which is often limited to <1 year from diagnosis. Virotherapy, based on the use of oncolytic viruses that exert anti-cancer effects by direct cell lysis and through the induction of anti-tumor immune response, represents an alternative therapeutic option for rare tumors with limited life expectancy. In this study, we propose the use of the adenovirus dl922-947, engineered to allow selective replication in cancer cells, to counteract MPM. Methods: We performed a thorough preclinical assessment of dl922-947 effects in a set of MPM cell lines and xenografts. Cytotoxicity of dl922-947 alone and in combination assays was evaluated by sulforhodamine B assay. Cell cycle, calreticulin expression, and high mobility group box protein 1 (HMGB1) secretion were determined by flow cytometry, whereas ATP content was determined by a luminescence-based bioassay. The modulation of angiogenic factors in MPM-infected cells was evaluated through ELISA. Results: We found that dl922-947 infection exhibits cytotoxic effects in MPM cell lines, affecting cell viability, cell cycle progression, and regulating main hallmarks of immunogenic cell death inducing calreticulin surface exposure, HMGB1 and ATP release. Our results also suggest that dl922-947 may affect angiogenic signals by regulation of VEGF-A and IL-8 secretion. Furthermore, dl922-947 shows anti-tumor efficacy in murine xenograft models reducing tumor growth and enhancing survival. Finally, the combination with cisplatin potentiated the cytotoxic effect of dl922-947. Conclusions: Overall our data identify virotherapy, based on the use of dl922-947, as a new possible therapeutic strategy against MPM, which could be used alone, in combination with standard chemotherapy drugs, as shown here, or other approaches also aimed at enhancing the antitumoral immune response elicited by the virus.}, } @article {pmid31336692, year = {2019}, author = {Krówczyńska, M and Wilk, E}, title = {Environmental and Occupational Exposure to Asbestos as a Result of Consumption and Use in Poland.}, journal = {International journal of environmental research and public health}, volume = {16}, number = {14}, pages = {}, pmid = {31336692}, issn = {1660-4601}, mesh = {Asbestos/*analysis ; Construction Materials ; Environmental Exposure/*analysis ; Female ; Humans ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology ; Mesothelioma, Malignant ; Poland/epidemiology ; }, abstract = {UNLABELLED: Asbestos is harmful to human health; exposure to asbestos causes a wide range of asbestos-related diseases.

AIM: Malignant mesothelioma (MM) is unique to occupational and environmental asbestos exposure.

METHODS: Environmental asbestos exposure was examined in relation to asbestos use and manufacturing, the quantity of the asbestos-containing products still in use, the concentrations of asbestos fibres in the air and the number of MM cases diagnosed each year per county.

RESULTS: The correlation coefficient of the measurements of the asbestos fibre concentrations in the air and the quantity of asbestos-cement products in use is high and amounts to 0.68. Meanwhile, the correlation coefficient of the measurements of asbestos fibre concentrations in air and MM morbidity rate resulting from environmental exposure calculated for particular counties in provinces is low and amounts to 0.37. The highest MM morbidity rate was observed for Małopolskie and Śląskie, a typical industrial area of Poland.

CONCLUSIONS: There are MM cases which are still attributable to occupational asbestos exposure, although MM cases resulting from environmental exposure to asbestos have an increased MM risk. Poland is among those countries with a low MM incidence rate, which seems to be an underestimation of environmental asbestos exposure. As long as asbestos-cement products are used in the environment, actions should be undertaken to protect public health.}, } @article {pmid31328588, year = {2019}, author = {Korchevskiy, A and Rasmuson, JO and Rasmuson, EJ}, title = {Empirical model of mesothelioma potency factors for different mineral fibers based on their chemical composition and dimensionality.}, journal = {Inhalation toxicology}, volume = {31}, number = {5}, pages = {180-191}, doi = {10.1080/08958378.2019.1640320}, pmid = {31328588}, issn = {1091-7691}, mesh = {Asbestos, Amphibole/toxicity ; Asbestos, Crocidolite/toxicity ; Asbestos, Serpentine/toxicity ; Humans ; Lung Neoplasms/*chemically induced ; Mesothelioma/*chemically induced ; Mesothelioma, Malignant ; Mineral Fibers/*toxicity ; *Models, Biological ; }, abstract = {Context: The potency of various mineral fiber types to produce mesothelioma was previously evaluated for numerous cohorts, but the differences in potencies for distinct fiber types have yet to be explained. Objective: To develop an empirical model that would reconstruct mesothelioma potency factors for various types of fiber based on their chemical composition and dimensionality. Methods: Typical chemical composition and dimensionality metrics (aspect ratios) were obtained and combined with mesothelioma potency factors estimated by Hodgson and Darnton method for Quebec chrysotile, South Africa amosite, South Africa and Australian crocidolite, Russian anthophyllite, Libby amphiboles, and Turkey erionite. The forward stepwise log-log regression method was utilized to determine the best combination of input parameters. Results: Mesothelioma potency factors (RM) for selected cohorts were effectively reconstructed utilizing the median aspect ratio of fibers and equivalent fractions of SiO2, total Fe oxides or total equivalent Fe[3+] as Fe2O3, and MgO. Modeled potency factors increase as the aspect ratio, SiO2, and total Fe oxide (or Fe2O3) content grow, and as the MgO content diminishes. Correlation coefficients up to 0.999, p < 0.01, were achieved. The models also yield reasonable estimates of mesothelioma potencies for other fiber types, including Bolivian crocidolite, Russian chrysotile, fluoro-edenite, and others. Conclusion: In spite of the empirical approach, the proposed models provide a starting point for targeted studies of mesothelioma mechanisms by elucidating significant contributing physicochemical factors. The models have an exploratory and preliminary character but can potentially be useful to introduce quantitative structure-activity relationship approaches for the toxicology of fibrous minerals.}, } @article {pmid31314677, year = {2020}, author = {Henley, SJ and Peipins, LA and Rim, SH and Larson, TC and Miller, JW}, title = {Geographic Co-Occurrence of Mesothelioma and Ovarian Cancer Incidence.}, journal = {Journal of women's health (2002)}, volume = {29}, number = {1}, pages = {111-118}, pmid = {31314677}, issn = {1931-843X}, support = {CC999999/ImCDC/Intramural CDC HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/toxicity ; Carcinoma, Ovarian Epithelial/*epidemiology ; Female ; Humans ; Incidence ; Lung Neoplasms/epidemiology/etiology ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Exposure/adverse effects ; Ovarian Neoplasms/*epidemiology ; Registries ; United States/epidemiology ; }, abstract = {Background: Asbestos is an established cause of several cancers, including mesothelioma and ovarian cancer. Incidence of mesothelioma, the sentinel asbestos-associated cancer, varies by state, likely reflecting different levels of asbestos exposure. We hypothesized that states with high mesothelioma incidence may also have high ovarian cancer incidence. Materials and Methods: Using data from the Centers for Disease Control and Prevention National Program for Cancer Registries and the National Cancer Institute Surveillance, Epidemiology, and End Results Program, we examined the geographic co-occurrence of mesothelioma and ovarian cancer incidence rates by U.S. state for 2003-2015. Results: By state, mesothelioma incidence ranged from 0.5 to 1.3 cases per 100,000 persons and ovarian cancer incidence ranged from 9 to 12 cases per 100,000 females. When states were grouped by quartile of mesothelioma incidence, the average ovarian cancer incidence rate was 10% higher in states with the highest mesothelioma incidence than in states with the lowest mesothelioma incidence. Ovarian cancer incidence tended to be higher in states with high mesothelioma incidence (Pearson correlation r = 0.54; p < 0.0001). Conclusions: Data from state cancer registries show ovarian cancer incidence was positively correlated with mesothelioma incidence, suggesting asbestos may be a common exposure. The potential for asbestos exposure has declined since the 1970s because fewer products contain asbestos; however, some products, materials, and buildings may still release asbestos and thousands of workers may be exposed. Ensuring that people are protected from exposure to asbestos in their workplaces, homes, schools, and communities may reduce the risk of several cancers.}, } @article {pmid31295974, year = {2019}, author = {Zona, A and Iavarone, I and Buzzoni, C and Conti, S and Santoro, M and Fazzo, L and Pasetto, R and Pirastu, R and Bruno, C and Ancona, C and Bianchi, F and Forastiere, F and Manno, V and Minelli, G and Minerba, A and Minichilli, F and Stoppa, G and Pierini, A and Ricci, P and Scondotto, S and Bisceglia, L and Cernigliaro, A and Ranzi, A and Comba, P and , and , and , }, title = {[SENTIERI: Epidemiological Study of Residents in National Priority Contaminated Sites. Fifth Report].}, journal = {Epidemiologia e prevenzione}, volume = {43}, number = {2-3 Suppl 1}, pages = {1-208}, doi = {10.19191/EP19.2-3.S1.032}, pmid = {31295974}, issn = {1120-9763}, mesh = {Adolescent ; Adult ; Aged ; Cause of Death ; Child ; Child, Preschool ; Congenital Abnormalities/epidemiology/etiology ; Endocrine Disruptors/toxicity ; Environmental Exposure/adverse effects ; Environmental Pollution/*adverse effects ; Environmental Restoration and Remediation ; Female ; Humans ; Incidence ; Industrial Waste/adverse effects ; Infant ; Infant, Newborn ; Italy/epidemiology ; Male ; Middle Aged ; Neoplasms/epidemiology/etiology ; Pregnancy ; Young Adult ; }, abstract = {INTRODUCTION AND OBJECTIVES: This volume provides an update of the health status of the populations living in the National Priority Contaminated Sites (NPCSs) included in the SENTIERI Project. This update is part of an epidemiological surveillance programme carried out in NPCSs, promoted by the Italian Ministry of Health as a further step of a project started in 2006, when the health status of residents in contaminated sites was first addressed within the National Strategic Program "Environment and Health". The Report focuses on five health outcomes: mortality, cancer incidence, hospital discharges, congenital anomalies, and children, adolescents and young adults' health. A key element of SENTIERI project is the a priori evaluation of the epidemiological evidence of a causal association between the considered cause of disease and the exposure. When an a priori evidence is identified, it is given a greater importance in the comment of the study findings.

METHODS: The present update of the SENTIERI Project concerns 45 NPCSs including in all 319 Italian Municipalities (out of over 8,000 Municipalities), with an overall population of 5,900,000 inhabitants at the 2011 Italian Census. Standardized Mortality Ratios (SMRs) and Standardized Hospitalization Ratios (SHRs), referring to a time window of 2006-2013, were computed for all the 45 NPCSs, using as a reference the corresponding mortality and hospitalization rates of the Regions where each NCPS is located. Standardized Incidence Ratios (SIRs) were computed by the Italian Association of Cancer Registries (AIRTUM) for the 22 NPCSs served by a Cancer Registry. AIRTUM covers about 56% of Italy, with partly different time-windows. SIRs have been estimated using as reference population the 4 macroareas in which Italy is divided (North-West, North-East, Centre, South). Prevalence of congenital anomalies was computed for 15 NPCSs.

RESULTS: An all-cause excess of 5,267 and 6,725 deaths was observed, respectively, in men and women; the cancer death excess was of 3,375 in men and 1,910 in women. It was estimated an excess of cancer incidence of 1,220 case in men and 1,425 in women over a five-year time window. With regard to the diseases with an a priori environmental aetiological validity, an excess for malignant mesothelioma, lung, colon, and gastric cancer, and for non-malignant respiratory diseases was observed. Cancer excess mainly affected NPCSs with presence of chemical and petrochemical plants, oil refineries, and dumping hazardous wastes. An excess of non-malignant respiratory disease was also detected in NPCSs in which steel industries and thermoelectric plants were present. An excess of mesothelioma was observed in NPCSs characterized by presence of asbestos and fluoro-edenite; it was also observed where the presence of asbestos was not reported in the legislative national decrees which define the NPCS areas. It is worth noting that, even if the presence of asbestos is not reported in many NPCSs legislative decrees, petrochemical plants and steel industries, for instance, are often characterized by the presence of a large amount of this mineral that, in the past, was extensively used as an insulating material. For the first time, the present Report includes a focus on the health status of children and adolescents (1,160,000 subjects, aged 0-19 years), and young adults (660,000 subjects, aged 20-29 years). Among infants (0-1 year), an excess of 7,000 hospitalizations was observed, 2,000 of which due to conditions of perinatal origin. In the age class 0-14, an excess of 22,000 hospitalizations for all causes was observed; 4,000 of them were due to acute respiratory diseases, and 2,000 to asthma. Data on cancer incidence for subjects aged 0-24 years were derived from general population cancer registries for twenty NPCSs, and from children cancer registries (age group: 0-19 years) for six NPCSs; 666 cases where diagnosed in the age group 0-24 years, corresponding to an excess of 9%. The main contributions to this excess are from soft tissue sarcomas in children (aged 0-14 years), acute myeloid leukaemia in children (aged 0-14 years) and in the age group 0-29 years, non-Hodgkin lymphoma and testicular cancer in young adults (aged 20-29 years). In seven out of 15 NPCSs, an excess prevalence rate of overall congenital anomalies at birth was observed. Congenital anomalies excesses included the following sites: genital organs, heart, limbs, nervous system, digestive system, and urinary system.

CONCLUSIONS: The main findings of SENTIERI Project have been the detection of excesses for the diseases which showed an a priori epidemiological evidence of a causal association with the environmental exposures specific for each considered NPCS. These observations are valuable within public health, because they contribute to priority health promotion activities. Looking ahead, the health benefits of an improved environmental quality might be appreciated in terms of reduction of the occurrence of adverse health effects attributable to each Site major pollutant agents. Due to the methodological approach of the present study, it was not possible to adjust for several confounding factors reported to be risk factors for the studied diseases (e.g., smoking, alcohol consumption, obesity). Even if excesses of mortality, hospitalization, cancer incidence, and prevalence of congenital anomalies were found in several NPCSs, the study design and the multifactorial aetiology of the considered diseases do not permit, for all of them, to draw conclusions in terms of causal links with environmental contamination. Moreover, it must be taken into consideration that economic factors and the availability of health services may also play a relevant role in a diseases outcome. A few observations regarding some methodological limitations of SENTIERI Project should be made. There is not a uniform environmental characterisation of the studied NPCSs in term of quality and detection of the pollutants, because this information is present in different databases which at present are not adequately connected. Moreover, the recognition of a contaminated site as a National Priority Site is based on soil and groundwater pollution, and the available information on air quality is currently sparse and not homogenous. Another limitation, in term of statistical power, is the small population size of many NPCSs and the low frequency of several health outcomes. A special caution must be paid in data interpretation when considering the correspondence between the contaminated areas and the municipality boundaries, as they do not always coincide perfectly: in some cases, a small municipality with a large industrial site, while in other settings only a part of the municipality is exposed to the sources of pollution. Furthermore, all available health information systems are currently accessible at municipality level. The real breakthrough is essentially comprised of the development and fostering of a networking system involving all local health authorities and regional environmental protection agencies operating in the areas under study. The possibility to integrate the geographic approach of SENTIERI Project with a set of ad hoc analytic epidemiological investigations, such as residential cohort studies, case control studies, children health surveys, biomonitoring surveys, and with socioepidemiological studies, might greatly contribute to the identification of health priorities for environmental remediation activities. Finally, as discussed in the last section of the report, there is a need to adopt, in each NPCS, a two-way oriented communication plan involving public health authorities, scientific community, and resident population, taking into account that the history, the cultural frame and the network of relationships specific of each local context play a major role in the risk perception perspective.}, } @article {pmid31290725, year = {2022}, author = {Mumma, MT and Sirko, JL and Boice, JD and Blot, WJ}, title = {Mesothelioma mortality within two radiation monitored occupational cohorts.}, journal = {International journal of radiation biology}, volume = {98}, number = {4}, pages = {786-794}, doi = {10.1080/09553002.2019.1642540}, pmid = {31290725}, issn = {1362-3095}, mesh = {*Asbestosis ; Humans ; *Lung Neoplasms/etiology ; *Mesothelioma/etiology ; Nuclear Power Plants ; *Occupational Diseases ; *Occupational Exposure/adverse effects ; *Radiation Exposure/adverse effects ; Thorax ; }, abstract = {PURPOSE: The risk of mesothelioma, including cancers of the pleura and peritoneum, was examined within two large cohorts of workers monitored for exposure to ionizing radiation.

METHODS AND MATERIALS: Mortality was assessed among 253,632 workers routinely monitored for external radiation, including 30,724 industrial radiographers (IR) at shipyards, 142,583 workers at nuclear power plants (NPP), and 83,441 IR who had not worked at an NPP or shipyard. Follow-up was from 1969 through 2011. Standardized mortality ratios (SMRs) and 95% confidence intervals (CIs) were computed; observed numbers of deaths from mesothelioma (including cancers of the pleura and peritoneum) and asbestosis were compared with numbers expected based on age-, sex-, and calendar year-specific national mortality rates. Job history and quantitative asbestos exposure data were unavailable, but work at a shipyard was taken as a surrogate for the likelihood of exposure. Cox proportional hazards models were used to estimate hazard ratios (HRs) for mesothelioma in relation to estimated cumulative radiation exposure to the lung.

RESULTS: The mean duration of follow-up was 25.3 years (max 42 years). The mean cumulative lung dose was 28.6 mGy (7.3% > 250 mGy). Nearly 20% of the workers had died by 2011. A total of 421 mesothelioma deaths were found (75% occurring after 1999) with increased SMRs among workers monitored in shipyards (SMR 9.97; 95% CI 8.50-11.63) and for NPP workers (SMR 5.55; 95% CI 4.88-6.29), but not for IR who had not worked in shipyards (SMR 1.15; 95% CI 0.53-2.19). Likewise, deaths from asbestosis (n = 189) were also increased for shipyard and NPP workers (SMR = 18.1 and 9.2, respectively), but not among workers who never worked at a shipyard or NPP (SMR = 0.70; n = 1). Radiation dose to the lung was not associated with a statistically meaningful dose-response trend for mesothelioma in the combined cohorts (HR at 100 mGy = 1.10; 95% CI 0.96-1.27; p = .18), nor was mesothelioma risk associated with radiation exposure among IR who had not worked in a shipyard and assumed minimally exposed to asbestos.

CONCLUSIONS: An elevated rate of death from mesothelioma was observed in two radiation-exposed occupational groups with potential for asbestos exposure. The increased risk of death from asbestosis, combined with little evidence of a rising trend in mesothelioma mortality with increasing radiation exposure, suggests that the mesothelioma (and asbestosis) excess in these workers was due to asbestos exposure in shipyards and power plants and not to occupational low-dose radiation.}, } @article {pmid31289611, year = {2019}, author = {Williams, M and Cheng, YY and Kirschner, MB and Sarun, KH and Schelch, K and Winata, P and McCaughan, B and Kao, S and Van Zandwijk, N and Reid, G}, title = {Transcriptional suppression of the miR-15/16 family by c-Myc in malignant pleural mesothelioma.}, journal = {Oncotarget}, volume = {10}, number = {41}, pages = {4125-4138}, pmid = {31289611}, issn = {1949-2553}, abstract = {MicroRNA downregulation is frequent in malignant pleural mesothelioma (MPM), but the mechanisms responsible for loss of miR-15/16 and miR-193a are yet to be elucidated and were investigated in this study. Copy Number Variation (CNV) of microRNA-coding genes was analyzed in MPM cells by digital droplet PCR (ddPCR) and revealed heterozygous loss of miR-193a and miR-15a/16-1, but no change in miR-15b/16-2. Epigenetic control of microRNA expression was inferred following decitabine and Trichostatin A (TSA) treatment which did not substantially affect microRNA expression. Knockdown of c-Myc expression led to upregulation of SMC4, miR-15b and 16, and to a lesser extent DLEU2 and miR-15a, whereas c-Myc overexpression repressed microRNA expression. Chromatin immunoprecipitation (ChIP) assays confirmed the interaction of c-Myc with the DLEU2 and SMC4 promoters. Tumor microRNA expression was determined in samples from MPM patients, with samples of pleura from cardiac surgery patients used as controls. In tumor samples, a strong correlation was observed between the expression of miR-15b and 16 (R[2]=0.793), but not miR-15a and 16. Our data suggest that in MPM, the downregulation of miR-15/16 is due to transcriptional repression by c-Myc, primarily via control of the miR-15b/16-2 locus, while miR-193a-3p loss is due to genomic deletion.}, } @article {pmid31289169, year = {2019}, author = {Taylor, L and Cooper, D and Aujayeb, A}, title = {Malignant deciduoid mesothelioma: a rare variant of epithelioid mesothelioma.}, journal = {BMJ case reports}, volume = {12}, number = {7}, pages = {}, pmid = {31289169}, issn = {1757-790X}, mesh = {Aged ; Asbestos/*adverse effects ; Deciduoma/*pathology ; Environmental Exposure ; Humans ; Lung Neoplasms/diagnostic imaging/metabolism/*pathology ; Male ; Mesothelioma/diagnostic imaging/metabolism/*pathology ; Mesothelioma, Malignant ; Palliative Care/methods ; Pleural Neoplasms/diagnostic imaging/pathology ; Prognosis ; Thoracoscopy/methods ; Tomography, X-Ray Computed/methods ; }, abstract = {We describe a case of a deciduoid mesothelioma, a rare variant of epithelioid mesothelioma, which is associated with a very poor prognosis. A review of the relevant literature is also included. The patient was a man with probable asbestos exposure and presented with classic features of pleural malignancy. Diagnosis was reached with close correlation between clinical, radiological and pathological findings.}, } @article {pmid31285358, year = {2019}, author = {Consonni, D and Calvi, C and De Matteis, S and Mirabelli, D and Landi, MT and Caporaso, NE and Peters, S and Vermeulen, R and Kromhout, H and Dallari, B and Pesatori, AC and Riboldi, L and Mensi, C}, title = {Peritoneal mesothelioma and asbestos exposure: a population-based case-control study in Lombardy, Italy.}, journal = {Occupational and environmental medicine}, volume = {76}, number = {8}, pages = {545-553}, pmid = {31285358}, issn = {1470-7926}, mesh = {Adult ; Aged ; Aged, 80 and over ; Case-Control Studies ; Environmental Exposure/*adverse effects ; Female ; Humans ; Italy/epidemiology ; Lung Neoplasms/*epidemiology/etiology ; Male ; Mesothelioma/*epidemiology/etiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/adverse effects ; Peritoneal Neoplasms/*epidemiology/etiology ; }, abstract = {OBJECTIVES: Asbestos is the main risk factor for peritoneal mesothelioma (PeM). However, due to its rarity, PeM has rarely been investigated in community-based studies. We examined the association between asbestos exposure and PeM risk in a general population in Lombardy, Italy.

METHODS: From the regional mesothelioma registry, we selected PeM cases diagnosed in 2000-2015. Population controls (matched by area, gender and age) came from two case-control studies in Lombardy on lung cancer (2002-2004) and pleural mesothelioma (2014). Assessment of exposure to asbestos was performed through a quantitative job-exposure matrix (SYN-JEM) and expert evaluation based on a standardised questionnaire. We calculated period-specific and gender-specific OR and 90% CI using conditional logistic regression adjusted for age, province of residence and education.

RESULTS: We selected 68 cases and 2116 controls (2000-2007) and 159 cases and 205 controls (2008-2015). The ORs for ever asbestos exposure (expert-based, 2008-2015 only) were 5.78 (90% CI 3.03 to 11.0) in men and 8.00 (2.56 to 25.0) in women; the ORs for definite occupational exposure were 12.3 (5.62 to 26.7) in men and 14.3 (3.16 to 65.0) in women. The ORs for ever versus never occupational asbestos exposure based on SYN-JEM (both periods) were 2.05 (90% CI 1.39 to 3.01) in men and 1.62 (0.79 to 3.27) in women. In men, clear positive associations were found for duration, cumulative exposure (OR 1.33 (1.19 to 1.48) per fibres/mL-years) and latency.

CONCLUSIONS: Using two different methods of exposure assessment we provided evidence of a clear association between asbestos exposure and PeM risk in the general population.}, } @article {pmid31283845, year = {2019}, author = {Carbone, M and Adusumilli, PS and Alexander, HR and Baas, P and Bardelli, F and Bononi, A and Bueno, R and Felley-Bosco, E and Galateau-Salle, F and Jablons, D and Mansfield, AS and Minaai, M and de Perrot, M and Pesavento, P and Rusch, V and Severson, DT and Taioli, E and Tsao, A and Woodard, G and Yang, H and Zauderer, MG and Pass, HI}, title = {Mesothelioma: Scientific clues for prevention, diagnosis, and therapy.}, journal = {CA: a cancer journal for clinicians}, volume = {69}, number = {5}, pages = {402-429}, pmid = {31283845}, issn = {1542-4863}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; R01 CA198138/CA/NCI NIH HHS/United States ; U01 CA214195/CA/NCI NIH HHS/United States ; }, mesh = {Antineoplastic Agents, Immunological/*therapeutic use ; Asbestos/adverse effects ; Australia/epidemiology ; Biomarkers, Tumor/*analysis/genetics/metabolism ; Carcinogenesis/chemically induced/genetics/pathology ; Combined Modality Therapy/methods ; Diagnostic Errors ; Europe/epidemiology ; Genetic Predisposition to Disease ; Germ-Line Mutation ; Global Burden of Disease ; Humans ; Incidence ; Inhalation Exposure/adverse effects ; International Cooperation ; Mesothelioma/diagnosis/epidemiology/etiology/*therapy ; Molecular Targeted Therapy/methods ; Occupational Exposure/adverse effects ; Pleura/drug effects/pathology/surgery ; Pleural Neoplasms/diagnosis/epidemiology/etiology/*therapy ; Pneumonectomy/*methods ; Prognosis ; Tumor Suppressor Proteins/genetics/metabolism ; Ubiquitin Thiolesterase/genetics/metabolism ; United States/epidemiology ; }, abstract = {Mesothelioma affects mostly older individuals who have been occupationally exposed to asbestos. The global mesothelioma incidence and mortality rates are unknown, because data are not available from developing countries that continue to use large amounts of asbestos. The incidence rate of mesothelioma has decreased in Australia, the United States, and Western Europe, where the use of asbestos was banned or strictly regulated in the 1970s and 1980s, demonstrating the value of these preventive measures. However, in these same countries, the overall number of deaths from mesothelioma has not decreased as the size of the population and the percentage of old people have increased. Moreover, hotspots of mesothelioma may occur when carcinogenic fibers that are present in the environment are disturbed as rural areas are being developed. Novel immunohistochemical and molecular markers have improved the accuracy of diagnosis; however, about 14% (high-resource countries) to 50% (developing countries) of mesothelioma diagnoses are incorrect, resulting in inadequate treatment and complicating epidemiological studies. The discovery that germline BRCA1-asssociated protein 1 (BAP1) mutations cause mesothelioma and other cancers (BAP1 cancer syndrome) elucidated some of the key pathogenic mechanisms, and treatments targeting these molecular mechanisms and/or modulating the immune response are being tested. The role of surgery in pleural mesothelioma is controversial as it is difficult to predict who will benefit from aggressive management, even when local therapies are added to existing or novel systemic treatments. Treatment outcomes are improving, however, for peritoneal mesothelioma. Multidisciplinary international collaboration will be necessary to improve prevention, early detection, and treatment.}, } @article {pmid31280996, year = {2019}, author = {Tsao, A and Nakano, T and Nowak, AK and Popat, S and Scagliotti, GV and Heymach, J}, title = {Targeting angiogenesis for patients with unresectable malignant pleural mesothelioma.}, journal = {Seminars in oncology}, volume = {46}, number = {2}, pages = {145-154}, doi = {10.1053/j.seminoncol.2019.06.001}, pmid = {31280996}, issn = {1532-8708}, mesh = {Asbestos/toxicity ; Bevacizumab/therapeutic use ; Carcinogenesis/*drug effects/genetics ; Humans ; Indoles/therapeutic use ; Lung Neoplasms/*drug therapy/genetics/pathology ; Mesothelioma/*drug therapy/genetics/pathology ; Mesothelioma, Malignant ; Neovascularization, Pathologic/*drug therapy/genetics/pathology ; Pleural Neoplasms/*drug therapy/genetics/pathology ; Quinazolines/therapeutic use ; }, abstract = {Malignant pleural mesothelioma (MPM) is a global health issue, the principal cause of which is exposure to asbestos. The prevalence is anticipated to rise over the next 2 decades, particularly in developing countries, due to the 30-50-year latency period between exposure to asbestos and carcinogenic development. Unresectable MPM has a poor prognosis and limited treatment options and, as such, there is a broad range of therapeutic targets of interest, including angiogenesis, immune checkpoints, mesothelin, as well as chemotherapeutic agents. Recently, the results of several randomized trials in the first-line setting combining antiangiogenic agents with chemotherapy have been reported. This review examines the scientific rationale for targeting angiogenesis in the treatment of unresectable MPM and analyzes recent clinical results with antiangiogenic agents in development (bevacizumab, nintedanib, and cediranib) for the management of MPM.}, } @article {pmid31273181, year = {2019}, author = {Terakawa, H and Gabata, R and Haba, Y and Takada, S and Sakamoto, K and Sasaki, M}, title = {[A Case of Peritoneal Mesothelioma Diagnosed by Ileus].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {46}, number = {6}, pages = {1081-1083}, pmid = {31273181}, issn = {0385-0684}, mesh = {Aged ; *Asbestos ; Humans ; *Ileus/etiology ; Male ; *Mesothelioma/complications ; *Peritoneal Neoplasms/complications ; }, abstract = {The present case involved a man aged about 70 years. He visited our hospital with the main complaint of abdominal pain. We diagnosed him with intestinal obstruction, and we decided to perform surgery. White knot sections were spread inside the abdominal cavity, and the small intestine appeared as a single block. This block was resected and examined for peritoneal mesothelioma. Peritoneal mesothelioma is thought to have incubation period of 20-25 years after exposure to asbestos, and the number of affected patients will increase in the future. In some cases, peritoneal mesothelioma occurs only in the peritoneum; therefore, diagnosis often becomes difficult. Once intestinal obstruction occurs, administering chemotherapy is difficult. Therefore, early diagnosis is thought to be very important.}, } @article {pmid31269586, year = {2019}, author = {Liu, XH and Wu, H and Huang, YF and Zhang, GY and Xu, MH}, title = {[Clinical characteristics of malignant peritoneal mesothelioma misdiagnosed as tuberculous peritonitis: a report of 6 cases].}, journal = {Zhonghua yi xue za zhi}, volume = {99}, number = {24}, pages = {1893-1897}, doi = {10.3760/cma.j.issn.0376-2491.2019.24.011}, pmid = {31269586}, issn = {0376-2491}, mesh = {Adult ; Aged ; Humans ; Male ; *Mesothelioma ; Middle Aged ; *Peritoneal Neoplasms ; *Peritonitis, Tuberculous ; Retrospective Studies ; }, abstract = {Objective: To reduce the misdiagnosis rate of ascites and improve the diagnosis rate of malignant peritoneal mesothelioma. Methods: From May 2008 to May 2018, in Xiangya Hospital of Central South University,the clinical data of malignant peritoneal mesothelioma misdiagnosed as tuberculous peritonitis were retrospectively analyzed. Results: (1) Among the 6 patients, they were male; the age of onset was 42-70 (52±9.57) years old, and there was no history of asbestos exposure. (2) All cases with abdominal pain or abdominal distension were there and the course of disease was more than 1 month to more than 2 years. (3) In all patients,the nature of ascites was exudate; ADA was higher than normal value and below 45 U/L; LDH value in ascites was higher than 200 U/L (83.3%); mesothelioma was considered in ascites cytology in 1 case. (4) Laparoscopic biopsy was performed in 2 cases and B-ultrasound guided biopsy in 4 cases; Among them, malignant peritoneal mesothelioma diagnosed by pathology. (5) In Immunohistochemical positive markers, MC was the most sensitive (100%), followed by CR (67%), CK-Pan (67%), Ki-67 (67%) and EMA (67%). (6) Two patients received treatment with operation, abdominal hyperthermic perfusion and postoperative systemic chemotherapy. Conclusions: (1) Malignant peritoneal mesothelioma should be considered in middle-aged and aged male patients with unexplained ascites and early laparoscopy or laparotomy for diagnosis. (2) ADA and LDH level in ascites are significant in differentiating tuberculous peritonitis from malignant peritoneal mesothelioma. (3) Immunohistochemical positive marker MC may be a potential specific marker for malignant mesothelioma. (4) The survival time of patients is improved by comprehensive treatment such as operation and chemotherapy.}, } @article {pmid31267149, year = {2019}, author = {Jiménez-Ramírez, C and Casjens, S and Juárez-Pérez, CA and Raiko, I and Del Razo, LM and Taeger, D and Calderón-Aranda, ES and Rihs, HP and Acosta-Saavedra, LC and Weber, DG and Cabello-López, A and Pesch, B and Ochoa-Vázquez, MD and Burek, K and Torre-Bouscoulet, L and Pérez-Padilla, JR and García-Bazan, EM and Brüning, T and Johnen, G and Aguilar-Madrid, G}, title = {Mesothelin, Calretinin, and Megakaryocyte Potentiating Factor as Biomarkers of Malignant Pleural Mesothelioma.}, journal = {Lung}, volume = {197}, number = {5}, pages = {641-649}, pmid = {31267149}, issn = {1432-1750}, mesh = {Aged ; Biomarkers, Tumor/*blood ; Calbindin 2/*blood ; Enzyme-Linked Immunosorbent Assay ; Female ; GPI-Linked Proteins/*blood ; Humans ; Incidence ; Lung Neoplasms/*blood/diagnosis/epidemiology ; Male ; Mesothelin ; Mesothelioma/*blood/diagnosis/epidemiology ; Mesothelioma, Malignant ; Mexico/epidemiology ; Middle Aged ; Pleural Neoplasms/*blood/diagnosis/epidemiology ; Predictive Value of Tests ; Prognosis ; Risk Assessment ; Risk Factors ; Sex Factors ; }, abstract = {PURPOSE: Malignant pleural mesothelioma (MPM) is a highly lethal cancer caused by exposure to asbestos. Currently, the diagnosis is a challenge, carried out by means of invasive methods of limited sensitivity. This is a case-control study to evaluate the individual and combined performance of minimally invasive biomarkers for the diagnosis of MPM.

METHOD: A study of 166 incident cases of MPM and 378 population controls of Mestizo-Mexican ethnicity was conducted. Mesothelin, calretinin, and megakaryocyte potentiating factor (MPF) were quantified in plasma by ELISA. The samples were collected from 2011 to 2016.

RESULTS: Based on ROC analysis and a preset specificity of 95%, the combination of the three biomarkers reached an AUC of 0.944 and a sensitivity of 82% in men. In women, an AUC of 0.937 and a sensitivity of 87% were reached. In nonconditional logistic regression models, the adjusted ORs in men were 7.92 (95% CI 3.02-20.78) for mesothelin, 20.44 (95% CI 8.90-46.94) for calretinin, and 4.37 (95% CI 1.60-11.94) for MPF. The ORs for women were 28.89 (95% CI 7.32-113.99), 17.89 (95% CI 3.93-81.49), and 2.77 (95% CI 0.47-16.21), respectively.

CONCLUSIONS: To our knowledge, this is the first study evaluating a combination of mesothelin, calretinin, and MPF, and demonstrating a sex effect for calretinin. The biomarker panel showed a good performance in a Mestizo-Mexican population, with high sensitivity and specificity for the diagnosis of MPM.}, } @article {pmid31265162, year = {2019}, author = {Numano, T and Higuchi, H and Alexander, DB and Alexander, WT and Abdelgied, M and El-Gazzar, AM and Saleh, D and Takase, H and Hirose, A and Naiki-Ito, A and Suzuki, S and Takahashi, S and Tsuda, H}, title = {MWCNT-7 administered to the lung by intratracheal instillation induces development of pleural mesothelioma in F344 rats.}, journal = {Cancer science}, volume = {110}, number = {8}, pages = {2485-2492}, pmid = {31265162}, issn = {1349-7006}, support = {//5th Term Long-Range Research Initiative (2017) by Japan Chemical Industry Association/ ; H22-kagaku-ippan-005//Ministry of Health, Labour and Welfare/ ; H22-kagaku-shitei-004//Ministry of Health, Labour and Welfare/ ; H25-kagaku-ippan-004//Ministry of Health, Labour and Welfare/ ; H27-kagaku-shitei-004//Ministry of Health, Labour and Welfare/ ; H28-kagaku-ippan-004//Ministry of Health, Labour and Welfare/ ; //Egyptian Cultural Affairs and Missions Sector/ ; }, mesh = {Animals ; Asbestos, Crocidolite/adverse effects ; Injections, Intraperitoneal/methods ; Lung/*drug effects ; Lung Neoplasms/*chemically induced/pathology ; Male ; Mesothelioma/*chemically induced/pathology ; Mesothelioma, Malignant ; Nanotubes, Carbon/*adverse effects ; Pleural Neoplasms/*chemically induced/pathology ; Rats ; Rats, Inbred F344 ; Trachea/drug effects/pathology ; }, abstract = {Multi-walled carbon nanotube-7 (MWCNT-7) fibers are biopersistent and have a structure similar to asbestos. MWCNT-7 has been shown to induce malignant mesothelioma when administered by intrascrotal or intraperitoneal injection in rats and mice, and an inhalation study demonstrated that rats exposed to respirable MWCNT-7 developed lung tumors. MWCNT-N, which is similar to MWCNT-7, was shown to induce both lung tumors and malignant mesothelioma in rats when administered by trans-tracheal intrapulmonary spraying (TIPS). The present study was performed to investigate the carcinogenicity of MWCNT-7 when administered by the TIPS method. Ten-week-old male F344/Crj rats were divided into 3 groups and administered 0.5 mL vehicle, 0.250 μg/mL MWCNT-7 or 0.250 μg/mL crocidolite once a week for 12 weeks (total doses of 1.5 mg/rat) and then observed for up to 104 weeks. Rats in the MWCNT-7 group began to die from pathologies associated with the development of malignant mesothelioma 35 weeks after the final TIPS administration. Overall, the incidence of malignant mesothelioma in the MWCNT-7 group was significantly higher than in the vehicle or crocidolite groups.}, } @article {pmid31262194, year = {2019}, author = {Guazzelli, A and Meysami, P and Bakker, E and Bonanni, E and Demonacos, C and Krstic-Demonacos, M and Mutti, L}, title = {What can independent research for mesothelioma achieve to treat this orphan disease?.}, journal = {Expert opinion on investigational drugs}, volume = {28}, number = {8}, pages = {719-732}, doi = {10.1080/13543784.2019.1638363}, pmid = {31262194}, issn = {1744-7658}, mesh = {Animals ; Antineoplastic Agents/*administration & dosage/pharmacology ; Drug Repositioning ; Humans ; Immunotherapy/methods ; Lung Neoplasms/*drug therapy/pathology ; Mesothelioma/*drug therapy/pathology ; Mesothelioma, Malignant ; Molecular Docking Simulation ; Molecular Targeted Therapy ; Pleural Neoplasms/*drug therapy/pathology ; Prognosis ; Rare Diseases/drug therapy/pathology ; Survival Rate ; }, abstract = {Introduction: Malignant pleural mesothelioma (MPM) is a rare neoplasm with a poor prognosis, as current therapies are ineffective. Despite the increased understanding of the molecular biology of mesothelioma, there is still a lack of drugs that dramatically enhance patient survival. Area Covered: This review discusses recent and complete clinical trials supported by the NIH, other U.S. Federal agencies, universities and organizations found on clinicaltrials.gov. Firstly, chemotherapy-based trials are described, followed by immunotherapy and multitargeted therapy. Then we introduce drug repositioning and the use of drug docking as tools to find new interesting molecules. Finally, we highlight potential molecular pathways that may play a role in mesothelioma biology and therapy. Expert Opinion: Numerous biases are present in the clinical trials due to a restricted number of cases, inappropriate endpoints and inaccurate stratification of patients which delay the finding of a treatment for MPM. The most crucial issue of independent research for MPM is the lack of more substantive funding to translate these findings to the clinical setting. However, this approach is not necessarily scientific given the low mutational load of mesothelioma relative to other cancers, and therefore patients need a more solid rationale to have a good chance of successful treatment.}, } @article {pmid31260913, year = {2019}, author = {Pyana Kitenge, J and Kapinga Kayembe, D and Tshibangu Muamba, M and Kachil Rubing, H and De Vos, B and Van Bouwel, J and Nemery, B}, title = {Malignant mesothelioma in Sub-Saharan Africa: A case report from Lubumbashi, DR Congo.}, journal = {Environmental research}, volume = {176}, number = {}, pages = {108556}, doi = {10.1016/j.envres.2019.108556}, pmid = {31260913}, issn = {1096-0953}, mesh = {Adult ; *Asbestos ; Congo ; Humans ; Lung Neoplasms/*diagnosis ; Male ; Mesothelioma/*diagnosis ; South Africa ; }, abstract = {Although asbestos has been used throughout Africa in the past decades, no reports of asbestos-related malignant mesothelioma are available from sub-Saharan Africa, except from South Africa and Zimbabwe. We present a case of a 39-year-old man who died from a histologically proven malignant mesothelioma of the peritoneum in Lubumbashi, DR Congo. No occupational exposure to asbestos could be found in his history. In view of his young age, we speculated that he had been exposed to asbestos as a child, which was highly plausible because he had grown up in one of the numerous mining estates of the region. The houses of these estates were often built with asbestos-containing materials, notably roofs made of corrugated asbestos-cement. The possibility of past domestic or environmental exposure to asbestos was substantiated by the identification of chrysotile and crocidolite fibres in samples of asbestos-cement collected from the home where the patient had lived as a child. To our knowledge, this is the first report of malignant mesothelioma from a country in the Central African region. We expect that heightened awareness and improved diagnosis will lead to the detection of more asbestos-related diseases in Africa.}, } @article {pmid31260832, year = {2019}, author = {Tsao, MS and Carbone, M and Galateau-Salle, F and Moreira, AL and Nicholson, AG and Roden, AC and Adjei, AA and Aubry, MC and Fennell, DA and Gomez, D and Harpole, D and Hesdorffer, M and Hirsch, FR and Liu, G and Malik, S and Nowak, A and Peikert, T and Salgia, R and Szlosarek, P and Taioli, E and Yang, H and Tsao, A and Mansfield, AS}, title = {Pathologic Considerations and Standardization in Mesothelioma Clinical Trials.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {14}, number = {10}, pages = {1704-1717}, doi = {10.1016/j.jtho.2019.06.020}, pmid = {31260832}, issn = {1556-1380}, mesh = {Biological Specimen Banks ; Biomarkers, Tumor/*genetics ; Clinical Trials as Topic/*standards ; Diagnosis, Differential ; Humans ; Mesothelioma/*classification/genetics/*pathology ; Pleural Neoplasms/*classification/genetics/*pathology ; }, abstract = {The accurate diagnosis of mesothelioma is critical for the appropriate clinical management of this cancer. Many issues complicate making the diagnosis of mesothelioma including the presence of reactive mesothelial cells in benign pleural effusions, the heterogeneity of mesothelioma histopathology, the relatively high incidence of other epithelial malignancies that metastasize to the pleura, and primary sarcomas that arise within the pleura. Given the rapidly evolving field of molecular profiling and the need for translational correlates in mesothelioma clinical trials, the National Cancer Institute (NCI)-International Association for the Study of Lung Cancer-Mesothelioma Applied Research Foundation Clinical Trials Planning Meeting was convened in March 2017 to develop a consensus on standard pathology guidelines for future NCI-sponsored clinical trials in mesothelioma. This consensus statement covers recommendations for specimen handling, pathologic classification and diagnosis, biobanking, and tissue correlative studies.}, } @article {pmid31239765, year = {2019}, author = {Ospina, D and Villegas, VE and Rodríguez-Leguizamón, G and Rondón-Lagos, M}, title = {Analyzing biological and molecular characteristics and genomic damage induced by exposure to asbestos.}, journal = {Cancer management and research}, volume = {11}, number = {}, pages = {4997-5012}, pmid = {31239765}, issn = {1179-1322}, abstract = {Asbestos is one of the most important occupational carcinogens. Currently, about 125 million people worldwide are exposed to asbestos in the workplace. According to global estimates, at least 107,000 people die each year from lung cancer, mesothelioma, and asbestosis as a result of occupational exposure to asbestos. The high pathogenicity of this material is currently known, being associated with the development of pulmonary diseases, of which lung cancer is the main cause of death due to exposure to this mineral. Pulmonary diseases related to asbestos are a common clinical problem and a major health concern worldwide. Extensive research has identified many important pathogenic mechanisms; however, the precise molecular mechanisms involved, and the generated genomic damage that lead to the development of these diseases, are not completely understood. The modes of action that underlie this type of disease seem to differ depending on the type of fiber, lung clearance, and genetics. This evidences the need to increase our knowledge about these effects on human health. This review focuses on the characteristics of asbestos and the cellular and genomic damage generated in humans via exposure.}, } @article {pmid31237454, year = {2019}, author = {Ledda, C and Caltabiano, R and Vella, F and Matera, S and Marconi, A and Loreto, C and Rapisarda, V}, title = {Fibulin-3 as biomarker of malignant mesothelioma.}, journal = {Biomarkers in medicine}, volume = {13}, number = {10}, pages = {875-886}, doi = {10.2217/bmm-2018-0285}, pmid = {31237454}, issn = {1752-0371}, mesh = {Asbestos/toxicity ; Biomarkers, Tumor/blood/*metabolism ; Databases, Factual ; ErbB Receptors/metabolism ; Extracellular Matrix Proteins/blood/*metabolism ; Humans ; Lung Neoplasms/chemically induced/mortality/*pathology ; Mesothelioma/chemically induced/mortality/*pathology ; Mesothelioma, Malignant ; Survival Rate ; }, abstract = {Many malignant diseases are associated with past asbestos exposure; the most lethal and strictly related to previous fiber exposure being malignant mesothelioma (MM). Effective preventive protocols may include sensitive and specific biomarkers. The role of Fb-3 has been recently investigated for MM early detection, but its role is still under debate. After an independent search for scientific literature, nine studies were included for a systematic review. Human Fb-3 levels seem to be able to separate healthy people with previous exposure to asbestiform fibers from MM patients. Fb-3 blood levels can distinguish MM effusions from other malignant and benign effusions. Furthers investigations on more significant groups of patients are desirable to validate and assess the validity of combining Fb-3 with other biomarkers.}, } @article {pmid31229775, year = {2019}, author = {Ramos-Bonilla, JP and Cely-García, MF and Giraldo, M and Comba, P and Terracini, B and Pasetto, R and Marsili, D and Ascoli, V and Lysaniuk, B and Rodríguez, MC and Mazzeo, A and Panqueva, RDPL and Baldión, M and Cañón, D and García-Herreros, LG and Pinzón, B and Hernández, LJ and Silva, YA}, title = {An asbestos contaminated town in the vicinity of an asbestos-cement facility: The case study of Sibaté, Colombia.}, journal = {Environmental research}, volume = {176}, number = {}, pages = {108464}, doi = {10.1016/j.envres.2019.04.031}, pmid = {31229775}, issn = {1096-0953}, mesh = {Adult ; *Asbestos/toxicity ; Cities ; Colombia ; Environmental Exposure ; Female ; Humans ; Incidence ; Male ; *Mesothelioma/epidemiology ; Middle Aged ; *Occupational Exposure ; }, abstract = {INTRODUCTION: The asbestos industry began operations in Colombia in 1942, with an asbestos-cement facility located in the municipality of Sibaté. In recent years residents from Sibaté have been complaining about what they consider is an unusually large number of people diagnosed with asbestos-related diseases in the town. A study to analyze the situation of Sibaté started in 2015, to verify if the number of asbestos related diseases being diagnosed were higher than expected, and to identify potential asbestos exposure sources in the town.

METHODS: A health and socioeconomic survey was implemented door-to-door to identify potential asbestos-related diseases. Several self-reported mesothelioma cases were identified, and for confirmation purposes, copies of the medical record with the histopathology report were obtained. A panel of six physicians analyzed the medical records. Information of validated cases was used to estimate the male and female age-adjusted incidence rate for Sibaté. Based on reports of the existence of potential asbestos-contaminated landfills, topographic maps, a digital elevation model, and current satellite images were crossed using a geographic information system to identify potential landfilled areas, and soils samples were collected in some of these areas.

RESULTS: A total of 355 surveys were completed, and 29 self-reported mesothelioma cases were identified. Twenty-five of these cases have been persons who had lived at some moment of their lives in Sibaté. It was possible to obtain copies of the medical diagnosis for 17 cases. Of these, the panel of physicians classified 15 cases as certain pleural mesothelioma, one as probable, and one as not mesothelioma. Based on this information, the estimated age-adjusted incidence rate of mesothelioma in Sibaté was 3.1 × 10[5] persons-year for males and 1.6 × 10[5] persons-year for females. These rates are high in comparison to those reported in other cities, regions, and countries of the world. Using geographic information systems, landfilled zones in the urban area of Sibaté were identified, on top of which a school and different sports facilities were built. The analysis of four soil samples collected in landfilled zones, confirmed the existence of an underground layer of friable and non-friable asbestos.

CONCLUSION: The collected evidence suggests the presence of a malignant pleural mesothelioma cluster in Sibaté.}, } @article {pmid31225962, year = {2019}, author = {Marsili, D and Canepa, A and Mossone, N and Comba, P}, title = {Environmental Health Education for Asbestos-Contaminated Communities in Italy: The Casale Monferrato Case Study.}, journal = {Annals of global health}, volume = {85}, number = {1}, pages = {}, pmid = {31225962}, issn = {2214-9996}, mesh = {Adolescent ; Adult ; Asbestos/*toxicity ; Construction Materials/*toxicity ; Curriculum ; Environmental Exposure/adverse effects ; Environmental Health/*education ; Female ; Humans ; Italy/epidemiology ; Lung Neoplasms/epidemiology ; Male ; Mesothelioma/epidemiology ; Mesothelioma, Malignant ; Occupational Exposure/adverse effects ; Peer Group ; Pleural Neoplasms/epidemiology ; *Schools ; }, abstract = {BACKGROUND: Environmental health education contributes towards increasing awareness of communities to prevent exposure to hazardous substances. Casale Monferrato, the operating site for the Eternit asbestos-cement factory from 1907 to 1986, is a prioritized asbestos-contaminated site for remediation in Italy. The area is prone to severe asbestos-related diseases. About 50 cases of mesothelioma are diagnosed in Casale Monferrato annually; mesothelioma has been shown to be caused by occupational, environmental and domestic asbestos exposure.

OBJECTIVES: The goal of this paper is to analyze the Casale Monferrato case study in terms of youth engagement in environmental health education initiatives on asbestos risk and health impact. The paper aims at underlining the lessons learned in order to share the success of this initiative with other communities living in asbestos-contaminated sites in different countries.

METHODS: Peer education methodology has been used through the Asbestos Classroom to involve teachers, students and other local stakeholders in training activities, in selection of the contents for educational materials and interactive tools, as well as in choosing the presentation process for the aforementioned knowledge sharing instruments.

FINDINGS: From November 2014 to June 2018, 185 high school students and teachers were trained through the Asbestos Classroom. Through December 2018, they trained 3,241 classroom visitors. The Classroom relies on an inclusive participative process in which young people play a key role in the network of relationships within their community.

CONCLUSIONS: The paper corroborates the importance of engaging the educational system in communication efforts aimed at fostering collective awareness on environmental risk and health-related impacts for communities living in industrially contaminated sites. Considering the global dimension of the asbestos contamination and disease burden, this experience might be of relevance both in countries that banned asbestos and in those where asbestos is not yet prohibited.}, } @article {pmid31211722, year = {2019}, author = {Metintas, M and Ak, G and Metintas, S and Yildirim, H and Dündar, E and Rahman, N}, title = {Prospective Study of the Utility of Computed Tomography Triage of Pleural Biopsy Strategies in Patients With Pleural Diseases.}, journal = {Journal of bronchology & interventional pulmonology}, volume = {26}, number = {3}, pages = {210-218}, doi = {10.1097/LBR.0000000000000559}, pmid = {31211722}, issn = {1948-8270}, support = {MCCC-RP-14-A17178/MCCC_/Marie Curie/United Kingdom ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Algorithms ; Female ; Humans ; *Image-Guided Biopsy/adverse effects/methods ; Male ; Mesothelioma/complications/*diagnostic imaging/pathology ; Middle Aged ; Patient Selection ; Pleura/diagnostic imaging/pathology ; Pleural Effusion/*diagnostic imaging/etiology ; Pleural Neoplasms/complications/*diagnostic imaging/pathology/secondary ; Predictive Value of Tests ; Prospective Studies ; Thoracoscopy ; *Tomography, X-Ray Computed ; Triage ; Tuberculosis, Pleural/complications/*diagnostic imaging/pathology ; Young Adult ; }, abstract = {BACKGROUND: This study aimed to prospectively evaluate the efficacy and reliability of a diagnostic workup, triaging pleural biopsy method according to baseline computerized tomography (CT) findings in the diagnosis of pleural diseases.

METHODS: Patients with pleural pathology were divided into 3 arms according to findings on CT scan images. Arm A: patients with pleural thickening/lesion in addition to pleural effusion. These patients underwent CT scan-guided Abrams' needle pleural biopsy. Arm B: patients with pleural effusion alone or suspected benign asbestos pleurisy. This group underwent medical thoracoscopy (MT). Arm C: patients with only pleural thickening. This group underwent ultrasonography-guided cutting needle pleural biopsy. MT was planned in patients who did not have a specific diagnosis in the CT scan-guided Abrams' needle pleural biopsy group. When patients with a histopathologic diagnosis of fibrinous pleuritis after MT were assessed in terms of the risk factors for malignant pleural diseases, we offered a further invasive procedure.

RESULTS: A total of 164 patients were enrolled in the study. Diagnostic sensitivity after the initial procedure was 90.2% in Arm A, 93.3% in Arm B, 95.2% in Arm C, and 92.4% in the entire workup. The negative predictive value of the entire workup was 90.4% for malignant pleural mesothelioma, 97.1% for metastatic malignant pleural diseases, and 100% for tuberculous pleurisy. Five cases who had a diagnosis of fibrinous pleuritis after MT were detected to have risk factors, 4 of which (80%) indicated malignant disease. Complication rates were low and acceptable.

CONCLUSION: Use of CT scans to triage an appropriate pleural biopsy method is associated with high diagnostic success. We recommend that the proposed diagnostic workup in this study may be used as a diagnostic algorithm for pleural diseases that require a histopathologic analysis. Determination of risk factors predicting malignant disease in patients where fibrinous pleuritis is reported after MT would be useful for clinical practice.}, } @article {pmid31207975, year = {2019}, author = {Catino, A and de Gennaro, G and Di Gilio, A and Facchini, L and Galetta, D and Palmisani, J and Porcelli, F and Varesano, N}, title = {Breath Analysis: A Systematic Review of Volatile Organic Compounds (VOCs) in Diagnostic and Therapeutic Management of Pleural Mesothelioma.}, journal = {Cancers}, volume = {11}, number = {6}, pages = {}, pmid = {31207975}, issn = {2072-6694}, abstract = {Malignant pleural mesothelioma (MPM) is a rare neoplasm related to asbestos exposure and with high mortality rate. The management of patients with MPM is complex and controversial, particularly with regard to early diagnosis. In the last few years, breath analysis has been greatly implemented with this aim. In this review the strengths of breath analysis and preliminary results in searching breath biomarkers of MPM are highlighted and discussed, respectively. Through a systematic electronic literature search, collecting papers published from 2000 until December 2018, fifteen relevant scientific papers were selected. All papers considered were prospective, comparative, observational case-control studies although every single one pilot and based on a relatively small number of samples. The identification of diagnostic VOCs pattern, through breath sample characterization and the statistical data treatment, allows to obtain a strategic information for clinical diagnostics. To date the collected data provide just preliminary information and, despite the promising results and diagnostic accuracy, conclusions cannot be generalized due to the limited number of individuals included in each cohort study. Furthermore none of studies was externally validated, although validation process is a necessary step towards clinical implementation. Breathomics-based biomarker approach should be further explored to confirm and validate preliminary findings and to evaluate its potential role in monitoring the therapeutic response.}, } @article {pmid31205069, year = {2020}, author = {Alchami, FS and Attanoos, RL and Gibbs, A and Morgan, F and Jasani, B}, title = {Does Simian Virus 40 (SV40) Have a Role in UK Malignant Pleural Mesothelioma? No Role is Identified in a Sensitive RNA In Situ Hybridization Study on Potentially Affected Birth Cohorts.}, journal = {Applied immunohistochemistry & molecular morphology : AIMM}, volume = {28}, number = {6}, pages = {444-447}, doi = {10.1097/PAI.0000000000000779}, pmid = {31205069}, issn = {1533-4058}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antigens, Polyomavirus Transforming/genetics/*metabolism ; Asbestos/*adverse effects ; Cell Transformation, Neoplastic/genetics ; Correlation of Data ; Female ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Male ; Mesothelioma, Malignant/etiology/genetics/*metabolism ; Middle Aged ; Pleural Neoplasms/etiology/genetics/*metabolism/pathology ; Poliovirus Vaccines/*adverse effects ; Retrospective Studies ; Simian virus 40/genetics/*metabolism ; United Kingdom ; }, abstract = {BACKGROUND: Simian virus 40 (SV40)-contaminated polio vaccine was accidentally administered to about one-third of the UK population receiving polio vaccines between 1956 and 1962. SV40 was subsequently demonstrated to be a carcinogenic virus in experimental and animal models. Since then, the SV40 oncogenic protein large T antigen (SV40 Tag) has been shown to cause malignant transformation of asbestos-treated human pleural mesothelial cells and malignant pleural mesotheliomas in asbestos-exposed SV40 Tag transgenic mice. The present study was designed to investigate the possible association of SV40 Tag with human malignant pleural mesothelioma samples from birth cohorts of the UK population exposed to combined peak levels of asbestos and SV40-contaminated polio vaccines.

MATERIALS AND METHODS: Tumor and background lung tissue microarrays prepared from archival surgical specimens of 139 pleural mesothelioma cases, collected over a period of 8 years (1998 to 2005), were analyzed. These represented birth cohorts overlapping with the period 1950 to 1960, exposed to a high level of both asbestos and SV40-contaminated live polio vaccines. SV40 Tag mRNA expression was investigated using a highly sensitive and specific SV40 Tag RNA in situ hybridization detection method on the basis of the novel RNAscope technology.

RESULTS: SV40 Tag RNA was not detected in any of the 127 evaluable tumor cases, despite appropriate results obtained for the external positive and negative controls included.

CONCLUSION: The complete absence of SV40 Tag mRNA in this large series of cases contradicts experimental evidence suggestive of SV40 link with asbestos-exposed malignant pleural mesotheliomas in the UK population. Alternative explanations of the negative findings are discussed to exclude possible confounding factors.}, } @article {pmid31200818, year = {2019}, author = {Tsim, S and Paterson, S and Cartwright, D and Fong, CJ and Alexander, L and Kelly, C and Holme, J and Evison, M and Blyth, KG}, title = {Baseline predictors of negative and incomplete pleural cytology in patients with suspected pleural malignancy - Data supporting 'Direct to LAT' in selected groups.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {133}, number = {}, pages = {123-129}, doi = {10.1016/j.lungcan.2019.05.017}, pmid = {31200818}, issn = {1872-8332}, support = {25355/CRUK_/Cancer Research UK/United Kingdom ; ETM/285/CSO_/Chief Scientist Office/United Kingdom ; }, mesh = {Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Biomarkers, Tumor ; Environmental Exposure/adverse effects ; Female ; Humans ; Lung Neoplasms/*diagnosis/pathology ; Male ; Pleura/*pathology ; Pleural Effusion, Malignant/*diagnosis/pathology ; Pleural Neoplasms/*diagnosis/pathology ; Predictive Value of Tests ; Prognosis ; Retrospective Studies ; }, abstract = {OBJECTIVES: Negative effusion cytology is more common in certain forms of Malignant Pleural Effusion (MPE) and results in pathway delay. Local Anaesthetic Thoracoscopy (LAT) is extremely sensitive and safe but cannot be offered to all. A stratified pathway, including 'Direct to LAT' in selected cases could enhance patient experience but requires reliable baseline predictors of unhelpful cytology, including both negative (no malignant cells) and incomplete results (malignant cells identified but predictive markers failed), since pleural biopsies will be required in the latter for optimal management. This retrospective analysis of a prospective multi-centre study, sought to identify baseline features for pathway rationalization.

MATERIALS AND METHODS: 363/638 (57%) of patients recruited to the DIAPHRAGM study (ISRCTN10079972) were included. Prospective data, including final diagnoses, asbestos exposure and fluid cytology results were supplemented by retrospective Computed Tomography (CT) and predictive marker reports. Independent predictors of negative and incomplete cytology were determined by multivariable logistic regression. Contingency tables were used to assess diagnostic value of cytology in associated phenotypes.

RESULTS: 238/363 (66%) patients were diagnosed with MPE (18 tumour types). Fluid cytology was negative in 151/238 (63%) and independently associated with asbestos-exposure (Odds Ratio (OR) 5.34) and a malignant CT (OR 2.25). When both features were recorded the sensitivity and negative predictive value of fluid cytology were 19% (95% CI 11-30%) and 9% (95% CI 4-20%)), respectively. Cytology was incomplete in 34/238 (14%), i.e. 47% of positive cytology cases) but was not associated with any baseline feature. ORs for incomplete cytology in Ovarian, Breast, Renal and Lung Cancer were 83, 22, 21 and 9, respectively.

CONCLUSION: Negative cytology is extremely likely in patients with asbestos exposure and a malignant CT report. A 'Direct-to-LAT' approach may be appropriate in this setting. No baseline predictors of incomplete cytology were identified.}, } @article {pmid31192957, year = {2019}, author = {Zan, X and Wang, Y and Shi, J and Zhao, L and Zhao, Y and Liu, R and Zhou, Y and Wan, Y and , }, title = {Biomarkers for detecting malignant pleural mesothelioma: Protocol for a reanalysis of published data based on systematic reviews of diagnostic test accuracy.}, journal = {Medicine}, volume = {98}, number = {24}, pages = {e16028}, pmid = {31192957}, issn = {1536-5964}, mesh = {Biomarkers, Tumor/metabolism ; Humans ; Lung Neoplasms/*metabolism ; Mesothelioma/*metabolism ; Mesothelioma, Malignant ; *Meta-Analysis as Topic ; Pleural Neoplasms/*metabolism ; *Systematic Reviews as Topic ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a highly invasive tumor caused primarily by asbestos exposure. In recent decades, the incidence of MPM has shown an increasing trend, posing a great threat to human health. Although there is currently no effective way to treat MPM, patients can survive for more than 5 years if the tumor is removed early. Several systematic reviews (SRs) have evaluated the diagnostic value of biomarkers for diagnosing MPM. However, no studies have been conducted to analyze the quality of these SRs and it remains unclear which biomarker is the excellent diagnostic test. This study aims to assess the methodological quality of the SRs and reanalyze the published data based on SRs to find the optimal biomarker for the early diagnosis of MPM.

METHODS: A systematic search will be performed in PubMed, Embase.com, the Cochrane Library of Systematic Reviews, and Web of Science to identify SRs reporting value of biomarkers for detecting MPM. We will evaluate the risk of bias of the included SRs according to the Assessment of Multiple Systematic Reviews-2 (AMSTAR-2) instrument. Standard pairwise meta-analysis and adjusted indirect comparison will be used to compare the diagnostic value of different biomarkers.

RESULTS: The results of this study will be submitted to a peer-reviewed journal for publication.

CONCLUSION: This study will reanalyze the published data based on SRs to find a biomarker with the superior diagnostic performance for the diagnosis of MPM.

ETHICS AND DISSEMINATION: Ethics approval and patient consent are not required as this study is an overview based on published systematic reviews.

PROSPERO REGISTRATION NUMBER: CRD42019125880.}, } @article {pmid31179006, year = {2019}, author = {Taylor, BH and Warnock, C and Tod, A}, title = {Communication of a mesothelioma diagnosis: developing recommendations to improve the patient experience.}, journal = {BMJ open respiratory research}, volume = {6}, number = {1}, pages = {e000413}, pmid = {31179006}, issn = {2052-4439}, mesh = {Asbestos/adverse effects ; Caregivers/*psychology ; *Communication ; Female ; Health Personnel/*psychology ; Humans ; Lung Neoplasms/*diagnosis/etiology/mortality/psychology ; Male ; Mesothelioma/*diagnosis/etiology/mortality/psychology ; Mesothelioma, Malignant ; *Professional-Patient Relations ; Prognosis ; Qualitative Research ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive cancer linked to asbestos exposure and inhalation. As with other cancers, receiving a diagnosis of MPM is challenging and distressing. Particular challenges are associated with communicating a diagnosis of MPM, including explaining the disease and its prognosis, treatment options and legal and financial implications. Receiving A Diagnosis Of Mesothelioma (RADIO Meso) aimed to understand the experience of communicating a diagnosis of MPM from the perspective of patients, family carers and health professionals.

METHODS: This qualitative study comprised 31 individual interviews with patients, family carers and health professionals. This was followed by two group interviews (n=42) and an electronic consultation exercise (n=39).

RESULTS: This study provides unique insight into the mesothelioma diagnostic experience of patients, family carers and health professionals. Key findings include the importance of regarding diagnosis as a process, and provision of continuity and consistency. The clinical nurse specialist and effective multidisciplinary team working provided vital contributions to successful mesothelioma diagnostic communication. Facilitators to diagnostic communication included honesty and timeliness in communication, partnership working and maintaining a patient-centred approach. Challenges to enhancing mesothelioma diagnosis communication included accessing ongoing training, ensuring a suitable clinical environment and being able to allocate appropriate time.

CONCLUSION: The RADIO Meso study highlights factors that influence the communication of a diagnosis of MPM from the perspectives of individual patients and family carers. These findings provide the basis for a set of recommendations that can be used by health professionals to improve the MPM diagnostic experience.}, } @article {pmid31171576, year = {2019}, author = {Takada, K and Fujimoto, N and Ozeki, T and Nishimura, J and Miyamoto, Y and Asano, M and Fuchimoto, Y and Wada, S and Ozaki, S and Igawa, T and Sonobe, H and Kishimoto, T}, title = {Small intestinal intussusception in an adult.}, journal = {Journal of clinical pathology}, volume = {72}, number = {7}, pages = {510}, doi = {10.1136/jclinpath-2017-204973}, pmid = {31171576}, issn = {1472-4146}, mesh = {Aged ; Autopsy ; Cell Proliferation ; Fatal Outcome ; Humans ; Intestine, Small/diagnostic imaging/pathology ; Intussusception/*diagnostic imaging/pathology ; Male ; Mesothelioma/*diagnostic imaging/pathology ; }, } @article {pmid31169558, year = {2019}, author = {Louw, A and Badiei, A and Creaney, J and Chai, MS and Lee, YCG}, title = {Advances in pathological diagnosis of mesothelioma: what pulmonologists should know.}, journal = {Current opinion in pulmonary medicine}, volume = {25}, number = {4}, pages = {354-361}, doi = {10.1097/MCP.0000000000000578}, pmid = {31169558}, issn = {1531-6971}, mesh = {Cyclin-Dependent Kinase Inhibitor p16/analysis ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; *Lung Neoplasms/diagnosis/pathology ; *Mesothelioma/diagnosis/pathology ; Mesothelioma, Malignant ; Pleural Effusion/*diagnosis/metabolism ; *Pleural Neoplasms/diagnosis/pathology ; Tumor Suppressor Proteins/analysis ; Ubiquitin Thiolesterase/analysis ; }, abstract = {PURPOSE OF REVIEW: Malignant pleural mesothelioma (MPM) is a universally fatal illness with a rising incidence, particularly in developing countries. The diagnosis can be challenging and require repeated investigations with implications for the patient and healthcare system.

RECENT FINDINGS: Distinguishing between benign/reactive and malignant mesothelial proliferations can be challenging. Cytological diagnosis of MPM from pleural fluid is as reliable as histological analysis of tissue biopsies in epithelioid MPM - an approach endorsed by the International Academy of Cytology. Identification of BRCA1-associated protein 1 (BAP1) and cyclin-dependent kinase inhibitor 2A (CDKN2A) gene mutations in MPM have led to the development of new ancillary tests that can streamline the diagnostic pathway. The prognostic values of these molecules are being investigated. Clinicians should be aware of the recently described BAP1 tumor predisposition syndrome and offer genetic investigations in potential patients. Routine use of prophylactic radiotherapy in MPM patients after pleural interventions has been disproved in a randomized trial.

SUMMARY: Diagnosis of epithelioid MPM can be established on pleural fluid analysis in most patients. The use of BAP1 immunostaining and CDKN2A/p16 fluorescence in-situ hybridization are particularly useful in distinguishing benign from malignant mesothelial proliferations. Clinicians should ensure these investigations are available in the pathological assessment of cases to minimize invasive investigations and the associated risks.}, } @article {pmid31166112, year = {2019}, author = {Santos Seoane, SM and Yano Escudero, R and Arenas García, V}, title = {An unexpected cause of dysphagia: pleural mesothelioma.}, journal = {Revista espanola de enfermedades digestivas}, volume = {111}, number = {6}, pages = {494-495}, doi = {10.17235/reed.2019.6024/2018}, pmid = {31166112}, issn = {1130-0108}, mesh = {Aged ; Deglutition Disorders/*etiology ; Humans ; Male ; Mesothelioma/*complications ; Pleural Neoplasms/*complications ; }, abstract = {Malignant mesothelioma usually originates from the pleura or peritoneum, and has a poor prognosis. The incidence of this type of tumor is increasing worldwide, which is probably a result of occupational or environmental exposure to asbestos. In 90% dyspnea, chest pain or a combination of both are usually the initial symptoms. Dysphagia only occurs in 1.4% and is very rare as the initial symptom. We present the case of a middle-aged patient, in whom the initial symptom was dysphagia, so an endoscopy was performed. This showed extrinsic compression of the esophagus that was demonstrated when performing the chest X-ray, in which it was revealed a posterior mediastinal mass surrounding the esophagus concentrically without mucosal invasion.}, } @article {pmid31158563, year = {2019}, author = {Konen, T and Johnson, JE and Lindgren, P and Williams, A}, title = {Cancer incidence and mortality associated with non-occupational and low dose exposure to Libby vermiculite in Minnesota.}, journal = {Environmental research}, volume = {175}, number = {}, pages = {449-456}, doi = {10.1016/j.envres.2019.04.004}, pmid = {31158563}, issn = {1096-0953}, mesh = {*Aluminum Silicates ; *Asbestos ; Asbestos, Amphibole ; Female ; Humans ; Incidence ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology ; Minnesota/epidemiology ; Montana ; Occupational Exposure/*statistics & numerical data ; }, abstract = {BACKGROUND: A vermiculite processing plant in a Minneapolis, Minnesota neighborhood utilized asbestos-containing ore from Libby, Montana from the late 1930's until 1989. Multiple pathways of exposure to Libby asbestos were characterized in a cohort of over 6000 plant workers and residents living near the plant.

OBJECTIVE: We conducted a cohort linkage study to assess the impact of cumulative low dose exposure and the role of occupational history on asbestos-related mortality and cancer morbidity among cohort members residing near a vermiculite plant.

METHODS: Cohort members alive in 1988 (n = 5848) were linked to the Minnesota Cancer Surveillance System to identify incident cases of mesothelioma, lung cancer, and all-cancer diagnosed from 1988 to 2010. Proportional incidence ratios (PIRs) were calculated for mesothelioma and lung cancer. Vital status and cause of death were ascertained from Minnesota vital records and the National Death Index (1988-2011). Mortality rates of the cohort (2001-2011) for asbestos-related outcomes were compared to the Minnesota population to estimate standardized mortality ratios (SMRs) and stratified by gender, exposure, and occupational history categories.

RESULTS: We identified seven cases of mesothelioma, with elevated incidence only in females (PIR = 11.76, 95% CI: 3.17, 30.12). Lung cancer was elevated in both genders: PIR = 1.54 (95% CI: 1.19, 2.0) in males and 1.62 (95% CI: 1.21, 2.12) in females. We found elevated mortality from COPD, lung cancer, and mesothelioma among females (SMR for mesothelioma in females = 18.97, CI: 3.91, 55.45), among the 546 deaths identified. All four deaths from mesothelioma occurred in the >75th percentile of exposure (>0.0156 fiber/cc x months). The SMR for lung cancer and all respiratory cancer was elevated even after controlling for occupation.

CONCLUSIONS: Community exposure to Libby amphibole asbestos from a vermiculite processing plant is associated with increased risk of COPD, lung cancer and mesothelioma incidence and mortality, most notably among females, and is likely to remain a public health issue for years to come.}, } @article {pmid31138176, year = {2019}, author = {Kettunen, E and Savukoski, S and Salmenkivi, K and Böhling, T and Vanhala, E and Kuosma, E and Anttila, S and Wolff, H}, title = {CDKN2A copy number and p16 expression in malignant pleural mesothelioma in relation to asbestos exposure.}, journal = {BMC cancer}, volume = {19}, number = {1}, pages = {507}, pmid = {31138176}, issn = {1471-2407}, support = {115372//Terveyden Tutkimuksen Toimikunta/ ; 109003//Työsuojelurahasto/ ; }, mesh = {Aged ; Asbestos/*adverse effects ; Chromosomes, Human/genetics ; Cyclin-Dependent Kinase Inhibitor p16/*genetics/*metabolism ; *DNA Copy Number Variations ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; In Situ Hybridization, Fluorescence ; Lung Neoplasms/chemically induced/genetics/*metabolism ; Male ; Mesothelioma/chemically induced/genetics/*metabolism ; Mesothelioma, Malignant ; Middle Aged ; Stromal Cells/metabolism ; Tissue Array Analysis ; }, abstract = {BACKGROUND: Deletion of the CDKN2A locus is centrally involved in the development of several malignancies. In malignant pleural mesothelioma (MPM), it is one of the most frequently reported genomic alteration. MPM is strongly associated with a patients' asbestos exposure. However, the status of CDKN2A and the expression of the corresponding protein, p16, in relation to MPM patient's asbestos exposure is poorly known. Copy number alterations in 2p16, 9q33.1 and 19p13 have earlier been shown to accumulate in lung cancer in relation to asbestos exposure but their status in MPM is unclear.

METHODS: We studied DNA copy numbers for CDKN2A using fluorescence in situ hybridization (FISH) and p16 expression by immunohistochemistry (IHC) in 92 MPM patients, 75 of which with known asbestos exposure status. We also studied, in MPM, copy number alterations in 2p16, 9q33.1 and 19p13 by FISH.

RESULTS: We were unable to detect an association between p16 expression and pulmonary asbestos fiber count in MPM tumor cells. However, significantly more MPM patients with high pulmonary asbestos fiber count (> 1 million fibers per gram [f/g]) had stromal p16 immunoreactivity than MPM of patients with low exposure (≤ 0.5 million f/g) (51.4% vs 16.7%; p = 0.035, Chi-Square). We found that an abnormal copy number of CDKN2A in MPM tumor cells associated with a high pulmonary asbestos fiber count (p = 0.044, Fisher's Exact test, two-tailed). In contrast to our earlier findings in asbestos associated lung cancer, DNA copy number changes in 2p16, 9q33 and 19p13 were not frequent in MPM although single cases with variable copy numbers on those regions were seen.

CONCLUSIONS: We found two instances where the gene locus CDKN2A or its corresponding protein expression, is associated with high asbestos exposure levels. This suggests that there may be biological differences between the mesotheliomas with high pulmonary asbestos fiber count and those with low fiber count.}, } @article {pmid31132706, year = {2019}, author = {Colombino, E and Capella, S and Casalinuovo, F and Racco, R and Pruiti, F and Volante, M and Di Marco Lo Presti, V and Belluso, E and Capucchio, MT}, title = {Malignant peritoneal mesothelioma in a boar who lived in Calabria (Italy): Wild animal as sentinel system of human health.}, journal = {The Science of the total environment}, volume = {683}, number = {}, pages = {267-274}, doi = {10.1016/j.scitotenv.2019.05.254}, pmid = {31132706}, issn = {1879-1026}, mesh = {Animals ; Asbestos/analysis ; Asbestosis/epidemiology/veterinary ; Environmental Exposure/*statistics & numerical data ; Environmental Monitoring/*methods ; Environmental Pollutants/analysis ; Humans ; Italy ; Lung Neoplasms/epidemiology/*veterinary ; Mesothelioma/epidemiology/*veterinary ; Mesothelioma, Malignant ; Swine ; }, abstract = {Mesothelioma is a tumor of the serosal membranes described both in human and veterinary medicine. While in humans the relationship between mesothelioma and exposure to asbestos and some other asbestiform minerals is well known, in animals it is still difficult to establish. In this paper a case of malignant peritoneal mesothelioma probably related to asbestos exposure in a wild boar is described. At post-mortem evaluation the peritoneum, diaphragm and serosal surface of liver and kidneys showed isolated to coalescent multiple nodular lesions. Samples from diaphragm, liver and lung were collected to perform microbiological and histological investigations. To assess the presence of asbestos and/or other asbestiform minerals, SEM-EDS investigations were performed on organs and soil samples collected from the area where the wild boar lived. Microbiological investigations were negative for Mycobacterium species. Gross and histological examination were compatible with a biphasic mesothelioma, with nodules composed of epithelioid and sarcomatoid elements with high pleomorphism. Immunohistochemistry revealed only multifocal scattered positivity for WT-1 and D2-40. Asbestos fibres were detected in all samples (organs and soil) by SEM-EDS, demonstrating a potential relationship between the neoplasia and the exposure to naturally occurring asbestos (NOA). In conclusion, the results of the present study are further confirmation that wild animals, such as the boar, are suitable sentinels to indicate the risk of environmental exposure to asbestos for human populations.}, } @article {pmid31120531, year = {2019}, author = {Chen, T and Sun, XM and Wu, L}, title = {High Time for Complete Ban on Asbestos Use in Developing Countries.}, journal = {JAMA oncology}, volume = {5}, number = {6}, pages = {779-780}, doi = {10.1001/jamaoncol.2019.0446}, pmid = {31120531}, issn = {2374-2445}, mesh = {Asbestos/*toxicity ; Carcinogens/*toxicity ; China ; Developing Countries ; Humans ; Mesothelioma/etiology/*prevention & control ; Occupational Diseases/etiology/*prevention & control ; Occupational Exposure/adverse effects/*prevention & control ; Pleural Neoplasms/etiology/*prevention & control ; }, } @article {pmid31120100, year = {2019}, author = {Kamiya, H and Peters, S and Sodhi-Berry, N and Reid, A and Gordon, L and de Klerk, N and Brims, F and Musk, AW and Franklin, P}, title = {Validation of an Asbestos Job-Exposure Matrix (AsbJEM) in Australia: Exposure-Response Relationships for Malignant Mesothelioma.}, journal = {Annals of work exposures and health}, volume = {63}, number = {7}, pages = {719-728}, doi = {10.1093/annweh/wxz038}, pmid = {31120100}, issn = {2398-7316}, mesh = {Adult ; Asbestos/*adverse effects ; Australia/epidemiology ; Humans ; Incidence ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Diseases/*epidemiology/etiology ; Occupational Exposure/*analysis ; Occupations/statistics & numerical data ; Proportional Hazards Models ; Young Adult ; }, abstract = {OBJECTIVES: An asbestos job-exposure matrix (AsbJEM) has been developed to systematically and cost-effectively evaluate occupational exposures in population-based studies. The primary aim of this study was to examine the accuracy of the AsbJEM in determining exposure-response relationships between asbestos exposure estimates and malignant mesothelioma (MM) incidence (indirect validation). The secondary aim was to investigate whether the assumptions used in the development of the original AsbJEM provided accurate asbestos exposure estimates.

METHODS: The study population consisted of participants in an annual health surveillance program, who had at least 3-month occupational asbestos exposure. Calculated asbestos exposure indices included cumulative asbestos exposure and the average exposure intensity, estimated using the AsbJEM and duration of employment. Asbestos and MM exposure-response relationships were compared between the original AsbJEM and its variations based on manipulations of the intensity, duration and frequency of exposure. Twenty-four exposure estimates were calculated for both cumulative asbestos exposure and the average exposure intensity using three exposure intensities (50th, 75th and 90th percentile of the range of mode exposure), four peak durations (15, 30, 60 and 120 min) and two patterns of peak frequency (original and doubled). Cox proportional hazards models were used to describe the associations between MM incidence and each of the cumulative and average intensity estimates.

RESULTS: Data were collected from 1602 male participants. Of these, 40 developed MM during the study period. There were significant associations between MM incidence and both cumulative and average exposure intensity for all estimates. The strongest association, based on the regression-coefficient from the models, was found for the 50th percentile of mode exposure, 15-min peak duration and the doubled frequency of peak exposure. Using these assumptions, the hazard ratios for mesothelioma were 1 (reference), 1.91, 3.24 and 5.37 for the quartiles of cumulative asbestos exposure and 1 (reference), 1.84, 2.31 and 4.40 for the quartiles of the average exposure intensity, respectively.

CONCLUSION: The well-known positive exposure-response relationship between MM incidence and both estimated cumulative asbestos exposure and average exposure intensity was confirmed. The strongest relationship was found when the frequency of peak exposure in the AsbJEM was doubled from the originally published estimates.}, } @article {pmid31119375, year = {2019}, author = {Galani, V and Varouktsi, A and Papadatos, SS and Mitselou, A and Sainis, I and Constantopoulos, S and Dalavanga, Y}, title = {The role of apoptosis defects in malignant mesothelioma pathogenesis with an impact on prognosis and treatment.}, journal = {Cancer chemotherapy and pharmacology}, volume = {84}, number = {2}, pages = {241-253}, doi = {10.1007/s00280-019-03878-3}, pmid = {31119375}, issn = {1432-0843}, mesh = {Apoptosis/*immunology ; Humans ; Lung Neoplasms/pathology/*therapy ; Mesothelioma/pathology/*therapy ; Mesothelioma, Malignant ; Prognosis ; }, abstract = {Malignant mesothelioma (MM) is a highly aggressive tumor that is strongly related to asbestos fiber exposure. The tumorigenesis procedure in MM is complex, and many pathogenetic mechanisms including chronic inflammation, deregulation of cell death, and the genomic copy-number losses and gains may contribute to carcinogenesis. MM cells are resistant to TRAIL-mediated apoptosis due to defects in extrinsic apoptotic pathway. CAPS, a regulator of cell cycle and death, may contribute to the MM development as well. BAP1 is the most frequently inactivated gene in MPM; BAP1 deficiency triggers malignant transformation via disruption of DNA repair, transcription regulation, cell metabolism, apoptosis, and ferroptosis. In addition, bcl-2 family proteins as well as abnormal activation of PI3 K/Akt/mTOR pathway and deregulation of the Wnt signaling pathway may result in MM tumorigenesis. Finally, the Hippo pathway plays a critical role in MPM development. Mutations of NF2 and LATS lead to YAP activation in MPM. Thus, inhibition of YAP activity by YAP inhibitors could be a potentially promising treatment option for MM. In conclusion, extensive genetic alterations exist in mesotheliomas associated with the signaling of apoptotic HM cells death. The comprehension of these pathways may contribute to enhancing survival via developing new effective therapeutic strategies.}, } @article {pmid31110054, year = {2019}, author = {Waqar, AB and Menzies, D and Casey, M and Doran, M}, title = {Paraneoplastic phenomenon in mesothelioma.}, journal = {Thorax}, volume = {74}, number = {7}, pages = {719-720}, doi = {10.1136/thoraxjnl-2019-213176}, pmid = {31110054}, issn = {1468-3296}, mesh = {Aged ; Biopsy ; Humans ; Lung Neoplasms/*complications/diagnostic imaging/pathology ; Male ; Mesothelioma/*complications/diagnostic imaging/pathology ; Mesothelioma, Malignant ; Ophthalmoplegia/*etiology ; Paraneoplastic Syndromes, Ocular/*etiology ; Pleural Effusion, Malignant/etiology ; Tomography, X-Ray Computed ; }, abstract = {A 71-year-old man presented with breathlessness and visual disturbance. On examination of the chest, he had signs suggestive of a right-sided pleural effusion and a neurological examination yielded conjugate vertical gaze palsy. Subsequent investigations revealed pleural thickening and mesothelioma. His anti-Ma2 antibodies were positive indicating a paraneoplastic syndrome as the cause of the vertical gaze palsy.}, } @article {pmid31107974, year = {2020}, author = {Milosevic, V and Kopecka, J and Salaroglio, IC and Libener, R and Napoli, F and Izzo, S and Orecchia, S and Ananthanarayanan, P and Bironzo, P and Grosso, F and Tabbò, F and Comunanza, V and Alexa-Stratulat, T and Bussolino, F and Righi, L and Novello, S and Scagliotti, GV and Riganti, C}, title = {Wnt/IL-1β/IL-8 autocrine circuitries control chemoresistance in mesothelioma initiating cells by inducing ABCB5.}, journal = {International journal of cancer}, volume = {146}, number = {1}, pages = {192-207}, doi = {10.1002/ijc.32419}, pmid = {31107974}, issn = {1097-0215}, mesh = {ATP Binding Cassette Transporter, Subfamily B/*genetics ; Animals ; Antineoplastic Agents/therapeutic use ; Cell Line, Tumor ; Drug Resistance, Neoplasm/*genetics ; Female ; Humans ; Interleukin-1beta/*metabolism ; Interleukin-8/*metabolism ; Mesothelioma/*drug therapy/metabolism/pathology ; Mice ; Mice, Inbred BALB C ; Mice, Knockout ; Pleural Neoplasms/*drug therapy/metabolism/pathology ; *Wnt Signaling Pathway ; }, abstract = {Malignant pleural mesothelioma (MPM) is a tumor with high chemoresistance and poor prognosis. MPM-initiating cells (ICs) are known to be drug resistant, but it is unknown if and how stemness-related pathways determine chemoresistance. Moreover, there are no predictive markers of IC-associated chemoresistance. Aim of this work is to clarify if and by which mechanisms the chemoresistant phenotype of MPM IC was due to specific stemness-related pathways. We generated MPM IC from primary MPM samples and compared the gene expression and chemo-sensitivity profile of IC and differentiated/adherent cells (AC) of the same patient. Compared to AC, IC had upregulated the drug efflux transporter ABCB5 that determined resistance to cisplatin and pemetrexed. ABCB5-knocked-out (KO) IC clones were resensitized to the drugs in vitro and in patient-derived xenografts. ABCB5 was transcriptionally activated by the Wnt/GSK3β/β-catenin/c-myc axis that also increased IL-8 and IL-1β production. IL-8 and IL-1β-KO IC clones reduced the c-myc-driven transcription of ABCB5 and reacquired chemosensitivity. ABCB5-KO clones had lower IL-8 and IL-1β secretion, and c-myc transcriptional activity, suggesting that either Wnt/GSK3β/β-catenin and IL-8/IL-1β signaling drive c-myc-mediated transcription of ABCB5. ABCB5 correlated with lower time-to-progression and overall survival in MPM patients treated with cisplatin and pemetrexed. Our work identified multiple autocrine loops linking stemness pathways and resistance to cisplatin and pemetrexed in MPM IC. ABCB5 may represent a new target to chemosensitize MPM IC and a potential biomarker to predict the response to the first-line chemotherapy in MPM patients.}, } @article {pmid31103412, year = {2019}, author = {Scagliotti, GV and Gaafar, R and Nowak, AK and Nakano, T and van Meerbeeck, J and Popat, S and Vogelzang, NJ and Grosso, F and Aboelhassan, R and Jakopovic, M and Ceresoli, GL and Taylor, P and Orlandi, F and Fennell, DA and Novello, S and Scherpereel, A and Kuribayashi, K and Cedres, S and Sørensen, JB and Pavlakis, N and Reck, M and Velema, D and von Wangenheim, U and Kim, M and Barrueco, J and Tsao, AS}, title = {Nintedanib in combination with pemetrexed and cisplatin for chemotherapy-naive patients with advanced malignant pleural mesothelioma (LUME-Meso): a double-blind, randomised, placebo-controlled phase 3 trial.}, journal = {The Lancet. Respiratory medicine}, volume = {7}, number = {7}, pages = {569-580}, doi = {10.1016/S2213-2600(19)30139-0}, pmid = {31103412}, issn = {2213-2619}, mesh = {Aged ; Antineoplastic Agents/*administration & dosage ; Antineoplastic Combined Chemotherapy Protocols ; Cisplatin/*administration & dosage ; Double-Blind Method ; Female ; Humans ; Indoles/*administration & dosage ; Lung Neoplasms/*drug therapy/mortality/pathology ; Male ; Mesothelioma/*drug therapy/mortality/pathology ; Mesothelioma, Malignant ; Middle Aged ; Pemetrexed/*administration & dosage ; Pleural Neoplasms/*drug therapy/mortality/pathology ; Progression-Free Survival ; }, abstract = {BACKGROUND: Nintedanib targets VEGF receptors 1-3, PDGF receptors α and β, FGF receptors 1-3, and Src and Abl kinases, which are all implicated in malignant pleural mesothelioma pathogenesis. Here, we report the final results of the phase 3 part of the LUME-Meso trial, which aimed to investigate the efficacy and safety of pemetrexed plus cisplatin combined with nintedanib or placebo in unresectable malignant pleural mesothelioma.

METHODS: This double-blind, randomised, placebo-controlled phase 3 trial was done at 120 academic medical centres and community clinics in 27 countries across the world. Chemotherapy-naive adults (aged ≥18 years) with unresectable epithelioid malignant pleural mesothelioma and ECOG performance status 0-1 were randomly assigned 1:1 via an independently verified random number-generating system to receive up to six 21-day cycles of pemetrexed (500 mg/m[2]) plus cisplatin (75 mg/m[2]) on day 1, then nintedanib (200 mg twice daily) or matched placebo on days 2-21. Patients without disease progression after six cycles received nintedanib or placebo maintenance on days 1-21 of each cycle. The primary endpoint was progression-free survival (investigator-assessed according to mRECIST) in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of their assigned study drug. This study is registered with ClinicalTrials.gov, number NCT01907100.

FINDINGS: Between April 14, 2016, and Jan 5, 2018, 541 patients were screened and 458 were randomly assigned to either the nintedanib group (n=229) or the placebo group (n=229). Median treatment duration was 5·3 months (IQR 2·8-7·3) in the nintedanib group and 5·1 months (2·7-7·8) in the placebo group. After 250 events, progression-free survival was not different between the nintedanib group (median 6·8 months [95% CI 6·1-7·0]) and the placebo group (7·0 months [6·7-7·2]; HR 1·01 [95% CI 0·79-1·30], p=0·91). The most frequently reported grade 3 or worse adverse event in both treatment groups was neutropenia (73 [32%] in the nintedanib group vs 54 [24%] in the placebo group). Serious adverse events were reported in 99 (44%) patients in the nintedanib group and 89 (39%) patients in the placebo group. The only serious adverse event occurring in at least 5% of patients in either group was pulmonary embolism (13 [6%] vs seven [3%]).

INTERPRETATION: The primary progression-free survival endpoint of the phase 3 part of LUME-Meso was not met and phase 2 findings were not confirmed. No unexpected safety findings were reported.

FUNDING: Boehringer Ingelheim.}, } @article {pmid31097089, year = {2019}, author = {MacRae, RM and Ashton, M and Lauk, O and Wilson, W and O'Rourke, N and Simone, CB and Rimner, A}, title = {The role of radiation treatment in pleural mesothelioma: Highlights of the 14th International Conference of the International mesothelioma interest group.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {132}, number = {}, pages = {24-27}, doi = {10.1016/j.lungcan.2019.03.023}, pmid = {31097089}, issn = {1872-8332}, mesh = {Animals ; Combined Modality Therapy ; Congresses as Topic ; Humans ; International Cooperation ; Mesothelioma/*radiotherapy ; Pleural Neoplasms/*radiotherapy ; Public Opinion ; Radiation Oncology/*trends ; Radiotherapy/*methods ; }, abstract = {Radiation remains an important component of mesothelioma treatment in 2018. Its use as a treatment modality continues to evolve as the technology for planning and delivery continues to improve. Use of radiation to improve local control in the involved hemithorax has been a common adjuvant treatment post extrapleural pneumonectomy for many years. Modern treatment options with advanced planning techniques including protons and intensity modulated radiation therapy lead to new potential options for treatment post lung-sparing surgery or in the unresectable setting. Presentations and discussions on the implementation of these strategies for palliation, treatment of oligometastatic recurrence or unresectable disease were the focus of a session dedicated to the role of radiation therapy at the 14[th] International Conference of the International Mesothelioma Interest Group and are reviewed in this article. Preclinical data to better understand how to integrate radiation and the delivery of novel systemic therapy approached like check point inhibitors are also presented.}, } @article {pmid31095409, year = {2019}, author = {Rosner, D and Markowitz, G and Chowkwanyun, M}, title = {"Nondetected": The Politics of Measurement of Asbestos in Talc, 1971-1976.}, journal = {American journal of public health}, volume = {109}, number = {7}, pages = {969-974}, pmid = {31095409}, issn = {1541-0048}, mesh = {Asbestos/*toxicity ; Carcinogens, Environmental/*adverse effects ; Cosmetics/*toxicity ; Humans ; Mesothelioma/chemically induced ; Mineral Fibers/adverse effects ; Particulate Matter/analysis ; Talc/*toxicity ; }, abstract = {The recent lawsuits against Johnson & Johnson have raised the issue of what and when talcum powder manufacturers knew about the presence of asbestos in their products and what they did or did not do to protect the public. Low-level exposure to asbestos in talc is said to result in either mesothelioma or ovarian cancer. Johnson & Johnson has claimed that there was "no detectable asbestos" in their products and that any possible incidental presence was too small to act as a carcinogen. But what exactly does "nondetected" mean? Here, we examine the historical development of the argument that asbestos in talcum powder was "nondetected." We use a unique set of historical documents from the early 1970s, when low-level pollution of talc with asbestos consumed the cosmetics industry. We trace the debate over the Food and Drug Administration's efforts to guarantee that talc was up to 99.99% free of chrysotile and 99.9% free of amphibole asbestos. Cosmetic talc powder manufacturers, through their trade association, pressed for a less stringent methodology and adopted the term "nondetected" rather than "asbestos-free" as a term of art.}, } @article {pmid31092657, year = {2019}, author = {de Boer, NL and van Kooten, JP and Burger, JWA and Verhoef, C and Aerts, JGJV and Madsen, EVE}, title = {Adjuvant dendritic cell based immunotherapy (DCBI) after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal mesothelioma, a phase II single centre open-label clinical trial: rationale and design of the MESOPEC trial.}, journal = {BMJ open}, volume = {9}, number = {5}, pages = {e026779}, pmid = {31092657}, issn = {2044-6055}, mesh = {Adjuvants, Immunologic/*therapeutic use ; Adult ; Antineoplastic Combined Chemotherapy Protocols ; Cancer Vaccines/*administration & dosage/*therapeutic use ; *Clinical Trials, Phase II as Topic ; *Cytoreduction Surgical Procedures ; Dendritic Cells/*immunology ; Feasibility Studies ; Female ; Humans ; *Hyperthermia, Induced ; Immunotherapy ; Lung Neoplasms/pathology/*therapy ; Male ; Mesothelioma/pathology/*therapy ; Mesothelioma, Malignant ; Middle Aged ; Peritoneal Neoplasms/pathology/*therapy ; Treatment Outcome ; }, abstract = {INTRODUCTION: Malignant peritoneal mesothelioma (MPM) is an uncommon but aggressive neoplasm and has a strong association with asbestos exposure. MPM has low survival rates of approximately 1 year even after (palliative) surgery and/or systemic chemotherapy. Recent advances in treatment strategies focusing on cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have resulted in improved median survival of 53 months and a 5 year survival of 47%. However, recurrence rates are high. Current systemic chemotherapy in the adjuvant setting is of limited efficacy, while immunotherapy with dendritic cell based immunotherapy (DCBI) has yielded promising results in murine models with peritoneal mesothelioma and in patients with pleural mesothelioma.

METHODS AND ANALYSIS: The MESOPEC trial is an open-label single centre phase II study. The study population are adult patients with histological/cytological confirmed diagnosis of epithelioid malignant peritoneal mesothelioma.

INTERVENTION: 4 to 6 weeks before CRS-HIPEC a leukapheresis is performed of which the monocytes are used for differentiation to dendritic cells (DCs). Autologous DCs pulsed with allogeneic tumour associated antigens (MesoPher) are re-injected 8 to 10 weeks after surgery, three times biweekly. Additional booster vaccinations are given at 3 and 6 months.Primary objective is to determine the feasibility of administering DCBI after CRS-HIPEC in patients with malignant peritoneal mesothelioma. Secondary objectives are to assess safety of DCBI in patients with peritoneal mesothelioma and determine whether a specific immunological response against the tumour occurs as a result of this adjuvant immunotherapy.

ETHICS AND DISSEMINATION: Permission to carry out this study protocol has been granted by the Central Committee on Research Involving Human Subjects (CCMO in Dutch) and the Research Ethics Committee (METC in Dutch). The results of this trial will be submitted for publication in a peer-reviewed journal.

TRIAL REGISTRATION NUMBER: NTR7060. EudraCT: 2017-000897-12; Pre-Results.}, } @article {pmid31087402, year = {2019}, author = {Loomis, D and Richardson, DB and Elliott, L}, title = {Quantitative relationships of exposure to chrysotile asbestos and mesothelioma mortality.}, journal = {American journal of industrial medicine}, volume = {62}, number = {6}, pages = {471-477}, pmid = {31087402}, issn = {1097-0274}, support = {P30 ES010126/ES/NIEHS NIH HHS/United States ; R01 OH007803/OH/NIOSH CDC HHS/United States ; R01-OH007803/OH/NIOSH CDC HHS/United States ; }, mesh = {Adult ; Age Factors ; Asbestos, Serpentine/*adverse effects/analysis ; Cohort Studies ; Confidence Intervals ; Environmental Monitoring/methods ; Evaluation Studies as Topic ; Female ; Humans ; Lung Neoplasms/*chemically induced/*mortality/physiopathology ; Male ; Maximum Allowable Concentration ; Mesothelioma/*chemically induced/*mortality/physiopathology ; Mesothelioma, Malignant ; Middle Aged ; North Carolina/epidemiology ; Occupational Diseases/etiology/mortality ; Occupational Exposure/*adverse effects/analysis ; Pleural Neoplasms/*chemically induced/*mortality/physiopathology ; Retrospective Studies ; Risk Assessment ; Sex Factors ; Survival Analysis ; Textile Industry ; }, abstract = {BACKGROUND: While asbestos has long been known to cause mesothelioma, quantitative exposure-response data on the relation of mesothelioma risk and exposure to chrysotile asbestos are sparse.

METHODS: Quantitative relationships of mortality from mesothelioma and pleural cancer were investigated in an established cohort of 5397 asbestos textile manufacturing workers in North Carolina, USA. Eligible workers were those employed between 1950 and 1973 with mortality follow-up through 2003. Individual exposure to chrysotile fibres was estimated on the basis of 3420 air samples covering the entire study period linked to work history records. Exposure coefficients adjusted for age, race, and time-related covariates were estimated by Poisson regression.

RESULTS: Positive, statistically significant associations were observed between mortality from all pleural cancer (including mesothelioma) and time since first exposure (TSFE) to asbestos (rate ratio [RR], 1.19; 95% confidence interval [CI], 1.06-1.34 per year), duration of exposure, and cumulative asbestos fibre exposure (RR, 1.15; 95% CI, 1.04-1.28 per 100 f-years/mL; 10-year lag). Analyses of the shape of exposure-response functions suggested a linear relationship with TSFE and a less-than-linear relationship with cumulative exposure. Restricting the analysis to years when mesothelioma was coded as a unique cause of death yielded stronger but less precise associations.

CONCLUSIONS: These observations support with quantitative data the conclusion that chrysotile causes mesothelioma and encourage exposure-response analyses of mesothelioma in other cohorts exposed to chrysotile.}, } @article {pmid31078776, year = {2019}, author = {Salaroglio, IC and Kopecka, J and Napoli, F and Pradotto, M and Maletta, F and Costardi, L and Gagliasso, M and Milosevic, V and Ananthanarayanan, P and Bironzo, P and Tabbò, F and Cartia, CF and Passone, E and Comunanza, V and Ardissone, F and Ruffini, E and Bussolino, F and Righi, L and Novello, S and Di Maio, M and Papotti, M and Scagliotti, GV and Riganti, C}, title = {Potential Diagnostic and Prognostic Role of Microenvironment in Malignant Pleural Mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {14}, number = {8}, pages = {1458-1471}, doi = {10.1016/j.jtho.2019.03.029}, pmid = {31078776}, issn = {1556-1380}, mesh = {Female ; Humans ; Lung Neoplasms/*diagnosis/pathology ; Male ; Mesothelioma/*diagnosis/pathology ; Mesothelioma, Malignant ; Prognosis ; Tumor Microenvironment ; }, abstract = {INTRODUCTION: A comprehensive analysis of the immune cell infiltrate collected from pleural fluid and from biopsy specimens of malignant pleural mesothelioma (MPM) may contribute to understanding the immune-evasion mechanisms related to tumor progression, aiding in differential diagnosis and potential prognostic stratification. Until now such approach has not routinely been verified.

METHODS: We enrolled 275 patients with an initial clinical diagnosis of pleural effusion. Specimens of pleural fluids and pleural biopsy samples used for the pathologic diagnosis and the immune phenotype analyses were blindly investigated by multiparametric flow cytometry. The results were analyzed using the Kruskal-Wallis test. The Kaplan-Meier and log-rank tests were used to correlate immune phenotype data with patients' outcome.

RESULTS: The cutoffs of intratumor T-regulatory (>1.1%) cells, M2-macrophages (>36%), granulocytic and monocytic myeloid-derived suppressor cells (MDSC; >5.1% and 4.2%, respectively), CD4 molecule-positive (CD4[+]) programmed death 1-positive (PD-1[+]) (>5.2%) and CD8[+]PD-1[+] (6.4%) cells, CD4[+] lymphocyte activating 3-positive (LAG-3[+]) (>2.8%) and CD8[+]LAG-3[+] (>2.8%) cells, CD4[+] T cell immunoglobulin and mucin domain 3-positive (TIM-3[+]) (>2.5%), and CD8[+]TIM-3[+] (>2.6%) cells discriminated MPM from pleuritis with 100% sensitivity and 89% specificity. The presence of intratumor MDSC contributed to the anergy of tumor-infiltrating lymphocytes. The immune phenotype of pleural fluid cells had no prognostic significance. By contrast, the intratumor T-regulatory and MDSC levels significantly correlated with progression-free and overall survival, the PD-1[+]/LAG-3[+]/TIM-3[+] CD4[+] tumor-infiltrating lymphocytes correlated with overall survival.

CONCLUSIONS: A clear immune signature of pleural fluids and tissues of MPM patients may contribute to better predict patients' outcome.}, } @article {pmid31078166, year = {2019}, author = {Labrèche, F and Kim, J and Song, C and Pahwa, M and Ge, CB and Arrandale, VH and McLeod, CB and Peters, CE and Lavoué, J and Davies, HW and Nicol, AM and Demers, PA}, title = {The current burden of cancer attributable to occupational exposures in Canada.}, journal = {Preventive medicine}, volume = {122}, number = {}, pages = {128-139}, doi = {10.1016/j.ypmed.2019.03.016}, pmid = {31078166}, issn = {1096-0260}, support = {//CIHR/Canada ; }, mesh = {Adolescent ; Adult ; Asbestos/toxicity ; Breast Neoplasms ; Canada/epidemiology ; Carcinogens/*toxicity ; Censuses ; Female ; Humans ; Lung Neoplasms ; Male ; Middle Aged ; Neoplasms/*epidemiology/etiology/prevention & control ; Occupational Diseases/*epidemiology ; Occupational Exposure/*statistics & numerical data ; Prevalence ; Silicon Dioxide/toxicity ; Skin Neoplasms ; Surveys and Questionnaires ; Young Adult ; }, abstract = {Exposure to occupational carcinogens is often overlooked as a contributor to the burden of cancer. To estimate the proportion of cancer cases attributable to occupational exposure in Canada in 2011, exposure prevalence and levels of 44 carcinogens were informed by data from the Canadian carcinogen exposure surveillance project (CAREX Canada). These were used with Canadian Census (between 1961 and 2011) and Labour Force Survey (annual surveys between 1976 and 2013) data to estimate the number of workers ever exposed to occupational carcinogens. Risk estimates of the association between each carcinogen and cancer site were selected mainly from published literature reviews. Population attributable risks were estimated using Levin's equation and applied to the 2011 cancer statistics from the Canadian Cancer Registry. It is estimated that 15.5 million Canadians alive in 2011 were exposed, during at least one year between 1961 and 2001, to at least one carcinogen in the workplace. Overall, we estimated that in 2011, between 3.9% (95% CI: 3.1%-8.1%) and 4.2% (95% CI: 3.3%-8.7%) of all incident cases of cancer were due to occupational exposure, corresponding to lower and upper numbers of 7700-21,800 cases. Five of the cancer sites - mesothelioma, non-melanoma skin cancer, lung, female breast, and urinary bladder - account for a total of 7600 to 21,200 cancers attributable to occupational exposures such as solar radiation, asbestos, diesel engine exhaust, crystalline silica, and night shift work. Our study highlights cancer sites and occupational exposures that need recognition and efforts by all stakeholders to avoid preventable cancers in the future.}, } @article {pmid31068670, year = {2019}, author = {Fitzgerald, RC and Rhodes, JM}, title = {Ingested asbestos in filtered beer, in addition to occupational exposure, as a causative factor in oesophageal adenocarcinoma.}, journal = {British journal of cancer}, volume = {120}, number = {12}, pages = {1099-1104}, pmid = {31068670}, issn = {1532-1827}, mesh = {Adenocarcinoma/*epidemiology/etiology ; Alcohol Drinking/*epidemiology ; Asbestos/*poisoning ; *Beer ; Esophageal Neoplasms/*epidemiology/etiology ; Food Contamination ; Humans ; Incidence ; Occupational Diseases/*epidemiology/etiology ; Occupational Exposure/statistics & numerical data ; }, abstract = {Oesophageal adenocarcinoma has become much more common over the past 50 years, particularly in Britain, with an unexplained male to female ratio of > 4:1. Given the use of asbestos filtration in commercial brewing and reports of its unregulated use in British public houses in the 1970's to clear draught beer "slops", we have assessed the hypothesis that ingested asbestos could be a causative factor for this increased incidence. Importantly, occupational asbestos exposure increases the risk of adenocarcinoma but not squamous cell carcinoma of the oesophagus. The presence of asbestos fibres was consistently reported in filtered beverages including beers in the 1970s and asbestos bodies have been found in gastrointestinal tissue, particularly oesophageal tissue, at autopsy. There is no reported association between the intake of alcohol and oesophageal adenocarcinoma but studies would mostly have missed exposure from draught beer before 1980. Oesophageal adenocarcinoma has some molecular similarities to pleural mesothelioma, a condition that is largely due to inhalation of asbestos fibres, including predominant loss of tumour suppressor genes rather than an increase of classical oncogenic drivers. Trends in incidence of oesophageal adenocarcinoma and mesothelioma are similar, rising rapidly over the past 50 years but now plateauing. Asbestos ingestion, either from beer consumed before around 1980, or from occupational exposure, seems a plausible causative factor for oesophageal adenocarcinoma. If this is indeed the case, its incidence should fall back to a low baseline by around 2050.}, } @article {pmid31057996, year = {2019}, author = {Barsky, AR and Cengel, KA and Katz, SI and Sterman, DH and Simone, CB}, title = {First-ever Abscopal Effect after Palliative Radiotherapy and Immuno-gene Therapy for Malignant Pleural Mesothelioma.}, journal = {Cureus}, volume = {11}, number = {2}, pages = {e4102}, pmid = {31057996}, issn = {2168-8184}, abstract = {Malignant pleural mesothelioma (MPM) is a highly aggressive disease, with few, if any, curative interventions. While there is growing interest in using immunotherapy and immuno-gene therapy to treat MPM, very limited data currently exist for combining these modalities with radiotherapy. Preclinical data suggest that radiotherapy may be combined with immunotherapy to produce disease regression, with abscopal effects in mice with MPM. We report the first-ever case of abscopal effect in a patient with MPM, following radiotherapy and immuno-gene therapy. The patient was a 67-year-old male with prior asbestos exposure who presented with progressive dyspnea and thoracic pain. He underwent partial right pleurectomy, pleural biopsy, and talc pleurodesis, with pathology revealing epithelioid MPM. A subsequent chest computed tomography (CT) scan and fluoro-deoxyglucose positron-emission tomography (FDG-PET) CT scan showed extensive, right-sided, fluoro-deoxyglucose (FDG) avid mass-like pleural thickening encasing the right lung, with likely mediastinal extension, nodal metastases, and vascular compression. He enrolled in a clinical trial in which he received intrapleural interferon-alpha gene therapy but needed to discontinue therapy due to supraventricular tachycardia and superior vena cava syndrome induced from tumor burden. He was emergently treated with palliative radiotherapy to 30 Gy in 10 fractions. He was then started on pemetrexed and cisplatin chemotherapy. His subsequent chest CT scan two months after radiotherapy completion showed a dramatic treatment response within, as well as outside of, the irradiated field. After completion of radiotherapy, he did experience radiation esophagitis requiring nasogastric tube placement. Herein, we highlight the feasibility and efficacy of combining immuno-gene therapy with palliative radiotherapy to produce a substantial treatment response and an abscopal effect in a patient with unresectable MPM.}, } @article {pmid31055741, year = {2019}, author = {Cui, Y and Zha, Y and Li, T and Bai, J and Tang, L and Deng, J and He, R and Dong, F and Zhang, Q}, title = {Oxidative effects of lungs in Wistar rats caused by long-term exposure to four kinds of China representative chrysotile.}, journal = {Environmental science and pollution research international}, volume = {26}, number = {18}, pages = {18708-18718}, doi = {10.1007/s11356-019-04978-6}, pmid = {31055741}, issn = {1614-7499}, support = {No. 41472046//National Natural Fund Project of China/ ; No. 41602033//National Natural Youth Fund Project of China/ ; No. YF17-Y12//the Fund Project of Sichuan Medical Law Research Center/ ; No. 2017LZXNYD-J24//Collaborative Fund of Luzhou Government and Southwest Medical University/ ; }, mesh = {Animals ; Asbestos, Serpentine/chemistry/*toxicity ; China ; Heme Oxygenase-1/metabolism ; Lipid Peroxidation/drug effects ; Lung/*drug effects/metabolism ; Lung Injury/*chemically induced/metabolism ; Male ; Oxidative Stress/*drug effects ; Particle Size ; Rats ; Rats, Wistar ; }, abstract = {Chrysotile accounts for some 90% to 95% of all the asbestos used worldwide. Scientific evidences have shown that asbestos (including chrysotile) exposure is associated with increased rates of lung cancer, asbestosis, and mesothelioma. However, molecular mechanisms underlying the toxicity effects of chrysotile are not clear. This study evaluated the oxidative stress in chronic lung toxicity caused by the intratracheal instillation (IT) of four kinds China representative chrysotile once a month for 12 months in Wistar rats. These results indicated that chrysotile exposure led to an obvious increase in lung mass and slowed the growth of body mass. Inflammation and fibrosis were observed by hematoxylin-eosin (HE) staining. Exposure to chrysotile significantly increased the accumulation of reactive oxygen species (ROS) and the level of lipid peroxidation and decreased antioxidant capacity in lung tissues. Furthermore, 1-6-month chrysotile exposure activated heme oxygenase-1 (HO-1) and heat shock protein 70 (HSP70) expression, whereas 12-month exposure caused significant decreases of two-factor expression levels in XK and MN groups when compared to negative control group. Therefore, our results suggested that chronic chrysotile pulmonary injury in Wistar rats is triggered by oxidative damage. Meanwhile, the oxidative damage of MN and XK was stronger than that of SSX and AKS, and the difference of oxidative damage in four chrysotile could have been brought by its properties, morphology, chemical composition, and particle size. With all the above mentioned in view, we hope that the revealed data in the experiment could contribute to the progress of further researches on the toxicity and mechanism of chrysotile.}, } @article {pmid31046484, year = {2019}, author = {Nowak, AK and McDonnell, A and Cook, A}, title = {Immune checkpoint inhibition for the treatment of mesothelioma.}, journal = {Expert opinion on biological therapy}, volume = {19}, number = {7}, pages = {697-706}, doi = {10.1080/14712598.2019.1606209}, pmid = {31046484}, issn = {1744-7682}, mesh = {Antibodies, Monoclonal/*therapeutic use ; B7-H1 Antigen/immunology/metabolism ; Biomarkers, Tumor/metabolism ; CTLA-4 Antigen/immunology/metabolism ; Drug Therapy, Combination ; Humans ; Immunotherapy ; Mesothelioma/*drug therapy/pathology ; Tumor Microenvironment ; }, abstract = {INTRODUCTION: Combination chemotherapy is currently standard care for advanced mesothelioma. Checkpoint blockade is a promising new treatment.

AREAS COVERED: This review covers clinical use and biomarkers of checkpoint blockade. Medline search used keywords 'mesothelioma' combined with 'checkpoint blockade' OR 'PD-L1' OR 'PD1' OR 'anti-CTLA4'; the search terms AND 'clinical trial' or AND 'biomarker*' were added. Handsearching covered abstracts from relevant meetings from 2016 to 2018 and reference lists. Data informed a narrative review.

EXPERT OPINION: Single agent anti-CTLA4 blockade is inactive in mesothelioma. Single agent PD-1 blockade as second or subsequent treatment gives 20-29% partial responses; no randomized comparisons against placebo or chemotherapy are available. Biomarkers of response have been difficult to identify. There is no consensus as to whether tumor PD-L1 expression predicts outcomes. Combination checkpoint inhibitors (CTLA4 and PD1 blockade) provide a small incremental increase in response rates and progression-free survival. Chemoimmunotherapy is the next frontier.}, } @article {pmid31046142, year = {2019}, author = {Macedo, RF and Cerqueira, EMFP and Algranti, E and Silva, D and De Capitani, EM}, title = {High frequency and severity of pleural changes in former workers exposed to anthophyllite associated with other contaminating amphibole asbestos in Brazil.}, journal = {American journal of industrial medicine}, volume = {62}, number = {6}, pages = {503-510}, doi = {10.1002/ajim.22977}, pmid = {31046142}, issn = {1097-0274}, mesh = {Aged ; Asbestos, Amphibole/*adverse effects/analysis ; Asbestosis/*epidemiology/etiology ; Brazil/epidemiology ; Cohort Studies ; Databases, Factual ; Environmental Monitoring/methods ; Female ; Humans ; Incidence ; Lung Neoplasms/chemically induced/*diagnosis/epidemiology ; Male ; Maximum Allowable Concentration ; Mesothelioma/chemically induced/*diagnosis/epidemiology ; Mesothelioma, Malignant ; Middle Aged ; Mining ; Occupational Exposure/*adverse effects ; Occupational Health ; Pleural Neoplasms/chemically induced/*epidemiology/physiopathology ; Retrospective Studies ; Risk Assessment ; Spirometry/methods ; Time Factors ; Vital Capacity ; }, abstract = {OBJECTIVE: To evaluate the frequency and severity of pleuropulmonary alterations in anthophyllite-exposed former workers in Itapira, São Paulo, Brazil. The amphibole anthophyllite, a magnesium-iron silicate, had its mining, marketing, and use forbidden in Brazil in 1995.

METHODS: Former workers were followed from 1999 to 2011. All completed chest X-ray interpreted using the International Labour Office (ILO) classification. High-resolution computed tomography was used at the final evaluation. Spirometry assessed forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and FEV1/FVC throughout the follow-up period. Samples from the mined ore were analyzed by X-ray diffraction (XRD) and scanning electron microscopy coupled to energy dispersive spectroscopy (SEM-EDS).

RESULTS: XRD and SEM-EDS confirmed the presence in ore of anthophyllite at a concentration of 75%, in addition to tremolite and other amphiboles in lower concentrations. Twenty-eight subjects were evaluated. Median time of exposure was 3 years (minimum = 1; maximum  = 18; interquartile interval = 1-4). Twenty cases of pleural abnormalities were diagnosed in 26 evaluated (77%). The average latency time was 25.6 ± 7.4 years. Two individuals (7.7%) showed progressive worsening of diffuse pleural thickening (DPT) and exhibited an annual FVC decrease of 85 mL and 150 mL, respectively.

CONCLUSION: This small sample showed a very high index of nonmalignant pleural abnormalities in anthophyllite-exposed workers compared with workers exposed to other kinds of fibers. Rapidly progressive DPT, defined by the severity of pleural compromise, was possibly secondary to the presence of other amphibole types in the inhaled dust. No significant loss of FVC was found in the studied group as a whole. No cases of asbestosis, lung carcinoma, and mesothelioma were diagnosed in this cohort.}, } @article {pmid31038674, year = {2019}, author = {Oey, H and Daniels, M and Relan, V and Chee, TM and Davidson, MR and Yang, IA and Ellis, JJ and Fong, KM and Krause, L and Bowman, RV}, title = {Whole-genome sequencing of human malignant mesothelioma tumours and cell lines.}, journal = {Carcinogenesis}, volume = {40}, number = {6}, pages = {724-734}, doi = {10.1093/carcin/bgz066}, pmid = {31038674}, issn = {1460-2180}, mesh = {Cell Line, Tumor ; Humans ; Mesothelioma/*genetics/pathology ; Mutation ; Pleural Neoplasms/*genetics/pathology ; *Whole Genome Sequencing ; }, abstract = {Pleural mesothelioma is a cancer of serosal surfaces caused by environmental exposure to asbestos. Clinical outcome remains poor and while trials of new treatments are ongoing it remains an understudied cancer. Mesothelioma cell lines can readily be grown from primary tumour and from tumour cells shed into pleural effusion with the latter representing a particularly valuable source of DNA in clinical settings, procurable without the need for additional invasive procedures. However, it is not well understood how accurately patient-derived cultured tumour cells represent the molecular characteristics of their primary tumour. We used whole-genome sequencing of primary tumour and matched cultured cells to comprehensively characterize mutations and structural alterations. Most cases had complex rearranged genomes with evidence of chromoanagenesis and rearrangements reminiscent of chromoplexy. Many of the identified driver mutations were structural, indicating that mesothelioma is often caused by structural alterations and catastrophic genomic events, rather than point mutations. Because the majority of genomic changes detected in tumours were also displayed by the genomes of cultured tumour cells, we conclude that low-passage cultured tumour cells are generally suitable for molecular characterization of mesothelioma and may be particularly useful where tissue samples with high tumour cell content are not available. However, the subclonal compositions of the cell lines did not fully recapitulate the subclonal diversity of the primary tumours. Furthermore, longitudinal acquisition of major alterations in subclonal cell populations was observed after long-term passaging. These two factors define limitations of tumour-derived cell lines as genomic substrate for clinical purposes.}, } @article {pmid31033031, year = {2019}, author = {Shih, AR and Kradin, RL}, title = {Malignant mesothelioma in Lynch syndrome: A report of two cases and a review of the literature.}, journal = {American journal of industrial medicine}, volume = {62}, number = {5}, pages = {448-452}, doi = {10.1002/ajim.22968}, pmid = {31033031}, issn = {1097-0274}, mesh = {Aged ; Asbestos/*adverse effects ; Colorectal Neoplasms, Hereditary Nonpolyposis/*genetics ; Female ; *Genetic Predisposition to Disease ; Humans ; Lung Neoplasms/*chemically induced/*genetics ; Mesothelioma/*chemically induced/*genetics ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/*adverse effects ; Risk Factors ; }, abstract = {Malignant mesothelioma is a rare and aggressive cancer most typically associated with prior asbestos exposure. The nature of the relationship between asbestos exposure and hereditary familial syndromes predisposing to malignancy has not been determined. We report two Lynch syndrome patients with paraoccupational asbestos exposure who developed diffuse malignant mesothelioma of the pleura or peritoneum. Interestingly, one showed a separate focus of pleural well-differentiated papillary mesothelioma. It is likely that Lynch syndrome patients are at increased risk for the development of mesothelioma in the setting of exposure to asbestos, even at what is generally considered to be low levels. In the presence of a documented history of low-level asbestos exposure, patients with genetic predisposition disorders (including Lynch syndrome) should be considered to have an independent risk factor modifying the effects of asbestos exposure.}, } @article {pmid31032152, year = {2019}, author = {Rakhra, A and Munir, A and Chilukuri, RS and Nahas, J}, title = {A Rare Case of Malignant Mesothelioma Presenting with Systemic Lupus Erythematosus Seropositivity: A Case Report and Review of Literature.}, journal = {Cureus}, volume = {11}, number = {2}, pages = {e4092}, pmid = {31032152}, issn = {2168-8184}, abstract = {While malignant mesothelioma may initially present in a variety of ways, it is uncommon to present with systemic lupus erythematosus (SLE) seropositivity and thus obscuring its diagnosis. Our case involves a 75-year-old Caucasian male with a past medical history of essential hypertension, remote prostate cancer status post prostatectomy, and lifetime nontobacco use presenting with progressive shortness of breath over one month. After a negative cardiac assessment, a postcardiac catheterization chest X-ray (CXR) revealed a right-sided moderate-to-large pleural effusion that, on further workup, was found to be exudative. Effusion studies were negative for malignancy and bacterial growth. Recurrent accumulation of fluid after a thoracentesis one week prior prompted an autoimmune work up. Positive markers included antinuclear antibodies, anti-double stranded DNA antibodies, and anti-histone antibodies, while anti-Smith antibodies were negative. Although SLE was initially suspected based on serologies, no clinical signs or symptoms were present to fulfill the diagnosis criteria. A trial of oral prednisone resulted in decreased pleural effusion size with no further recurrence. Additional studies included a CT scan of the chest that showed pleural masses confirmed with biopsy to be epithelioid mesothelioma. Given the patient's age and new diagnosis of malignant mesothelioma, we hypothesized that the presence of autoantibodies was likely false positives due to acquired autoantibodies with age, hyperactivity of the immune system from malignancy, and possible prior asbestos exposure.}, } @article {pmid31030080, year = {2019}, author = {Zona, A and Fazzo, L and Minelli, G and De Santis, M and Bruno, C and Conti, S and Comba, P}, title = {Peritoneal mesothelioma mortality in Italy: Spatial analysis and search for asbestos exposure sources.}, journal = {Cancer epidemiology}, volume = {60}, number = {}, pages = {162-167}, doi = {10.1016/j.canep.2019.04.001}, pmid = {31030080}, issn = {1877-783X}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Female ; Humans ; Italy ; Lung Neoplasms/*epidemiology/mortality ; Male ; Mesothelioma/*epidemiology/mortality ; Mesothelioma, Malignant ; Middle Aged ; Peritoneal Neoplasms/*epidemiology/mortality ; Spatial Analysis ; }, abstract = {BACKGROUND: This study is part of a national plan of epidemiological surveillance of malignant mesothelioma (MM) mortality in Italy. The paper shows the results of malignant peritoneal mesothelioma (MPeM) mortality study in Italian Regions and municipalities.

METHODS: National Bureau of Statistics data for MPeM municipal mortality (ICD-10, Code C45.1) were analyzed in the time-window 2003-2014: mortality standardized rates (reference Italian population, census 2011), temporal trends of the annual national rates, Standardized Mortality Ratios and a municipal clustering analysis were performed.

RESULTS: 747 deaths for MPeM were recorded (0.10/100,000): 464 in men (0.14/100,000) and in 283 women (0.07/100,000). No significant MPeM mortality temporal trend was found. Seventeen municipalities showed excesses of mortality for MPeM in at least one gender and/or overall population. Four clusters in male population, and one in women were identified.

CONCLUSIONS: The study identifies some areas where remediation activities and/or health care actions may be warranted.}, } @article {pmid31023248, year = {2019}, author = {Nagamatsu, Y and Oze, I and Aoe, K and Hotta, K and Kato, K and Nakagawa, J and Hara, K and Kishimoto, T and Fujimoto, N}, title = {Physician requests by patients with malignant pleural mesothelioma in Japan.}, journal = {BMC cancer}, volume = {19}, number = {1}, pages = {383}, pmid = {31023248}, issn = {1471-2407}, mesh = {Adult ; Aged ; Asbestos/*toxicity ; Environmental Exposure ; Female ; Humans ; Japan/epidemiology ; Lung Neoplasms/chemically induced/*epidemiology/pathology ; Male ; Mesothelioma/chemically induced/*epidemiology/pathology ; Mesothelioma, Malignant ; Middle Aged ; Palliative Care ; Physicians ; Pleural Neoplasms/chemically induced/*epidemiology/pathology ; Quality of Life ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a fatal and rare disease that is caused by the inhalation of asbestos. Treatment and care requests made by MPM patients to their physicians were collected and analyzed.

METHODS: This cross-sectional survey was part of a larger study (N = 133) regarding the quality of life of MPM patients. Specific responses to two open-ended questions related to patients' requests regarding treatment and care were quantified, analyzed and divided into categories based on content.

RESULTS: Responses (N = 217) from MPM patients (N = 73) were categorized into 24 subcategories and then abstracted into 6 categories. The majority of requests were related to patient-physician communication. Patients wanted clear and understandable explanations about MPM and wanted their physician to deliver treatment based on the patient's perspective by accepting and empathizing with their anxiety and pain. Patients expected physicians to be dedicated to their care and establish an improved medical support system for MPM patients.

CONCLUSION: Patients with MPM had a variety of unmet needs from their physicians. Physicians who provide care to MPM patients should receive training in both communication skills and stress management. A multidisciplinary care system that includes respiratory and palliative care for MPM patients should be established.}, } @article {pmid31022494, year = {2019}, author = {Christofidou-Solomidou, M and Pietrofesa, RA and Park, K and Albelda, SM and Serve, KM and Keil, DE and Pfau, JC}, title = {Synthetic secoisolariciresinol diglucoside (LGM2605) inhibits Libby amphibole fiber-induced acute inflammation in mice.}, journal = {Toxicology and applied pharmacology}, volume = {375}, number = {}, pages = {81-93}, pmid = {31022494}, issn = {1096-0333}, support = {R21 CA178654/CA/NCI NIH HHS/United States ; P30 ES013508/ES/NIEHS NIH HHS/United States ; P42 ES023720/ES/NIEHS NIH HHS/United States ; R03 CA180548/CA/NCI NIH HHS/United States ; R01 CA133470/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Asbestos, Amphibole/*toxicity ; Butylene Glycols/*pharmacology ; Female ; Glucosides/*pharmacology ; Inflammation/*chemically induced/*prevention & control ; Male ; Mice ; Mice, Inbred C57BL ; Organ Size ; Peritoneum/drug effects/pathology ; Spleen/drug effects/pathology ; }, abstract = {BACKGROUND: Exposure to the Libby amphibole (LA) asbestos-like fibers found in Libby, Montana, is associated with inflammatory responses in mice and humans, and an increased risk of developing mesothelioma, asbestosis, pleural disease, and systemic autoimmune disease. Flaxseed-derived secoisolariciresinol diglucoside (SDG) has anti-inflammatory, anti-fibrotic, and antioxidant properties. We have previously identified potent protective properties of SDG against crocidolite asbestos exposure modeled in mice. The current studies aimed to extend those findings by evaluating the immunomodulatory effects of synthetic SDG (LGM2605) on LA-exposed mice.

METHODS: Male and female C57BL/6 mice were given LGM2605 via gavage initiated 3 days prior to and continued for 3 days after a single intraperitoneal dose of LA fibers (200 μg) and evaluated on day 3 for inflammatory cell influx in the peritoneal cavity using flow cytometry.

RESULTS: LA exposure induced a significant increase (p < 0.0001) in spleen weight and peritoneal influx of white blood cells, all of which were reduced with LGM2605 with similar trends among males and females. Levels of peritoneal PMN cells were significantly (p < 0.0001) elevated post LA exposure, and were significantly (p < 0.0001) blunted by LGM2605. Importantly, LGM2605 significantly ameliorated the LA-induced mobilization of peritoneal B1a B cells.

CONCLUSIONS: LGM2605 reduced LA-induced acute inflammation and WBC trafficking supporting its possible use in mitigating downstream LA fiber-associated diseases.

SUMMARY: Following acute exposure to Libby amphibole (LA) asbestos-like fibers, synthetic SDG (LGM2605), a small synthetic molecule, significantly reduced the LA-induced increase in spleen weight and peritoneal inflammation in C57BL/6 male and female mice. Our findings highlight that LGM2605 has immunomodulatory properties and may, thus, likely be a chemopreventive agent for LA-induced diseases.}, } @article {pmid30993422, year = {2019}, author = {Boffetta, P and Donato, F and Pira, E and Luu, HN and La Vecchia, C}, title = {Risk of mesothelioma after cessation of asbestos exposure: a systematic review and meta-regression.}, journal = {International archives of occupational and environmental health}, volume = {92}, number = {7}, pages = {949-957}, pmid = {30993422}, issn = {1432-1246}, mesh = {Asbestos/*toxicity ; Carcinogens, Environmental/adverse effects ; Female ; Humans ; Lung Neoplasms/epidemiology/mortality ; Male ; Mesothelioma/*epidemiology/mortality ; Occupational Exposure/*adverse effects ; Peritoneal Neoplasms/epidemiology/mortality ; Pleural Neoplasms/epidemiology/mortality ; Risk Factors ; *Time Factors ; }, abstract = {PURPOSE: A 'risk reversal' has been observed for several human carcinogens following cessation of exposure, but it is unclear whether it also exists for asbestos-related mesothelioma.

METHODS: We conducted a systematic review of the literature and identified nine studies that reported information on risk of mesothelioma after cessation of asbestos exposure, and performed a meta-regression based on random effects models. As comparison we analyzed results on lung cancer risk from four of these studies.

RESULTS: A total of six risk estimates from five studies were included in the meta-analysis. The summary relative risk (RR) of mesothelioma for 10-year interval since cessation of exposure was 1.02 [95% confidence interval (CI) 0.87-1.19; p-heterogeneity 0.01]. The corresponding RR of lung cancer was 0.91 (95% CI 0.84-0.98).

CONCLUSIONS: This analysis provides evidence that the risk of mesothelioma does not decrease after cessation of asbestos exposure, while lung cancer risk does.}, } @article {pmid30968843, year = {2019}, author = {Fedrigotti, A and Riccadonna, A and Riccadonna, D}, title = {"Candido's List": the workers of Collotta Cis & Figli at Molina di Ledro in Trento Province, Italy. A tale of magnesia, asbestos and work.}, journal = {Annali dell'Istituto superiore di sanita}, volume = {55}, number = {1}, pages = {90-93}, doi = {10.4415/ANN_19_01_16}, pmid = {30968843}, issn = {2384-8553}, mesh = {Asbestos, Amosite/*adverse effects/history ; Environmental Restoration and Remediation ; Female ; History, 19th Century ; Humans ; Italy ; Magnesium/adverse effects ; Magnesium Oxide/adverse effects ; Male ; Mesothelioma/*epidemiology/etiology/history ; Occupational Diseases/etiology/history ; Occupational Exposure ; Pleural Neoplasms/*epidemiology/etiology/history ; }, abstract = {The study entitled "Candido's List" (La Lista di Candido) is not the work of the three authors alone. A good part of the community is entitled to feel itself coauthor, each for his/her own part, of a research project that has succeeded in blending a variety of different ingredients: history, entrepreneurship, the industrialization of the Trento Province with all its high and low points, personal life stories, medicine, genius, work, women's emancipation, the past but also the present and future. The research comprises an eloquent collection of memories and a variety of iconographic materials; it has now become a book and a travelling exhibition containing the accounts of the people who worked at the Collotta-Cis factory in Molina di Ledro. It starts with the brilliance of Pier Antonio Cassoni, who in 1816 deposited the first patent in the world for the extraction of magnesium carbonate, and closes with the decontamination of the factory site in the late 1980s. A needful section has been set aside for the painful facts relating to the processing of asbestos fibre; a final space, midway between an artistic reading and an interpretation for the future, has seen the involvement of the Circolo Fotoamatori di Ledro, with a photographic itinerary enabling the reader to "virtually' enter the remaining worksites and listen to these spaces "tell" their stories after years of silence. A story in black and white, where the two tones are also messages for reading a complex story, one that it is important to remember.}, } @article {pmid30968842, year = {2019}, author = {Parolari, G}, title = {An outbreak of cancer and asbestosis among former amosite-exposed subjects in Ledro Valley, Italy. From discovery to environmental cleanup.}, journal = {Annali dell'Istituto superiore di sanita}, volume = {55}, number = {1}, pages = {80-89}, doi = {10.4415/ANN_19_01_15}, pmid = {30968842}, issn = {2384-8553}, mesh = {Adolescent ; Adult ; Aged ; Asbestos ; Asbestos, Amosite/*adverse effects ; Asbestosis/*epidemiology/mortality ; Child ; Disease Outbreaks ; Environmental Restoration and Remediation/*methods ; Female ; Humans ; Italy/epidemiology ; Lung Neoplasms/epidemiology/etiology/mortality ; Male ; Mesothelioma/epidemiology/etiology/mortality ; Middle Aged ; Neoplasms/chemically induced/*epidemiology/mortality ; Occupational Exposure/statistics & numerical data ; Young Adult ; }, abstract = {Here are reviewed the studies conducted on asbestos-amosite pollution and its effects on the health of workers exposed from 1928 to 1973 at the Collotta-Cis factory of Ledro, Italy. The methods adopted to conduct the initial research, involving the population itself and the local administrations are described. The data summarized include: epidemiological studies of mortality carried out in 1977-85 and updated in 2009; results of the investigations carried out throughout the 1980s on the health consequences on workers, their families and residents near the factory; process of environmental cleanup from asbestos of the industrial area, completed in 1989, and the pollution risk assessment in the whole Ledro Valley. Although this was a small community of about 400 workers, these studies show that exposure to asbestos is responsible for the death of 81 people (22 mesotheliomas, 21 asbestosis, 38 malignant tumors of the lung, digestive system, ovary), for 1400 years of life lost, and for about 100 invalidity pensions, as recognized to former workers by INAIL.}, } @article {pmid30968841, year = {2019}, author = {Marsili, D and Magnani, C and Canepa, A and Bruno, C and Luberto, F and Caputo, A and Fazzo, L and Zona, A and Comba, P}, title = {Communication and health education in communities experiencing asbestos risk and health impacts in Italy.}, journal = {Annali dell'Istituto superiore di sanita}, volume = {55}, number = {1}, pages = {70-79}, doi = {10.4415/ANN_19_01_14}, pmid = {30968841}, issn = {2384-8553}, mesh = {Asbestos/*adverse effects ; Asbestosis/*epidemiology/prevention & control ; Communication ; Environmental Exposure ; Health Education/*statistics & numerical data ; Humans ; Incidence ; Italy/epidemiology ; Neoplasms/epidemiology/etiology ; Occupational Exposure ; Public Health Surveillance ; }, abstract = {INTRODUCTION: Numerous municipalities in Italy currently experience asbestos health impact, in particular excesses of pleural mesothelioma incidence and mortality. This paper presents an integrated analysis of epidemiological studies and communication actions in affected municipalities to highlight how communication has been implemented depending on health impact evidence and involvement of local stakeholders.

METHODOLOGY: Four case studies are identified concerning industrial and natural sources of asbestos exposure having different diseases burden. This integrated analysis benefited from multidisciplinary skills.

DISCUSSION: Evidence of different stakeholders engagement is presented to emphasize their role in the communication process. Similarities and differences among case studies allowed us to identify lessons-learned to be transferred in other asbestos contaminated sites.

CONCLUSIONS: The adoption of communication strategies and practices, since the very early evidence of asbestos health impact, represents a relevant contribution for epidemiological and health surveillance, particularly for those communities where asbestos health impact has only been recently reported.}, } @article {pmid30946862, year = {2019}, author = {Finkelstein, MM}, title = {A comparison of asbestos fiber potency and elongate mineral particle (EMP) potency for mesothelioma in humans.}, journal = {Toxicology and applied pharmacology}, volume = {371}, number = {}, pages = {1-2}, doi = {10.1016/j.taap.2019.03.023}, pmid = {30946862}, issn = {1096-0333}, mesh = {Air Pollutants, Occupational/*adverse effects ; Animals ; Asbestos/*adverse effects ; Mesothelioma/*chemically induced/diagnosis/epidemiology ; Mineral Fibers/adverse effects ; Occupational Exposure/*adverse effects ; Risk Assessment ; Risk Factors ; }, abstract = {Dr. Garabrant presented a paper concerning a comparison of asbestos fiber potency and elongate mineral particle (EMP) potency for mesothelioma in humans at the Elongate Mineral Particles Conference in Charlottesville, Virginia in 2017. I was a participant at the Conference. Following Dr. Garabrant's talk, I rose in question period to point out that he had not considered information about the occurrence of mesothelioma in several cohorts that was published after the studies that he cited. These additional data were still not addressed in the paper published in your Journal. I believe that your readers would be interested in these, so this letter is written to draw the additional data to their attention.}, } @article {pmid30944991, year = {2019}, author = {Warby, A and Dhillon, HM and Kao, S and Vardy, JL}, title = {A survey of patient and caregiver experience with malignant pleural mesothelioma.}, journal = {Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer}, volume = {27}, number = {12}, pages = {4675-4686}, pmid = {30944991}, issn = {1433-7339}, support = {n/a//New South Wales Workers' Compensation Dust Disease Board/ ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Caregivers/*psychology ; Decision Making ; Female ; Grief ; Health Personnel/*psychology ; Humans ; Lung Neoplasms/*psychology/*therapy ; Male ; Mesothelioma/*psychology/*therapy ; Mesothelioma, Malignant ; Middle Aged ; Palliative Care/methods ; Physician-Patient Relations ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare cancer with poor prognosis. As there is little information on the lived experience of MPM, our aim was to document the experience of MPM patients and their caregivers.

METHODS: Surveys for MPM patients and caregivers were developed from previous interviews with patients, caregivers, and health professionals, about treatments and decision-making. Participants were recruited from two hospitals, government compensation body, and support groups.

RESULTS: Survey responses were received from 78 MPM patients and 106 caregivers from January to September 2014.

PATIENTS: 85% male, median age 69 years, median time since diagnosis 15 months. Caregivers: median age 68, 91% female, 90% spouse of MPM patient, 95% bereaved. Most participants felt informed about treatment options but only 69% thought all treatment options were discussed. Chemotherapy was discussed most frequently (92-95%); ~80% had sufficient information for decision-making. Decision regarding chemotherapy was made by patient considering doctor's opinion (24%), doctor and patient equally (18%), and doctor (17%). Participants 'agreed'/'strongly agreed' that they made the right decision about chemotherapy (patients 81%, caregivers 60%), but 5% and 16%, respectively, regretted the decision. Most participants received 'sufficient' support (71%). A quarter reported seeing cancer nurse specialists. Palliative care referral: 31% patients, 85% caregivers. Caregivers would have liked to talk to someone by themselves (41%), more time with doctors (30%), psychological support (29%), and clearer information (31%). Bereaved caregivers requested grief counselling (39%) and post-death consultation with specialists (23-25%).

CONCLUSIONS: Satisfaction with treatment was high, but participants identified need for improved communication and quality information, discussion about all treatments, end-of-life assistance, and caregiver support after the patient's death.}, } @article {pmid30941506, year = {2019}, author = {Lococo, F and Di Stefano, T and Rapicetta, C and Piro, R and Gelli, MC and Muratore, F and Ricchetti, T and Taddei, S and Zizzo, M and Cesario, A and Facciolongo, N and Paci, M}, title = {Thoracic Hyper-IgG4-Related Disease Mimicking Malignant Pleural Mesothelioma.}, journal = {Lung}, volume = {197}, number = {3}, pages = {387-390}, pmid = {30941506}, issn = {1432-1750}, mesh = {Aged ; Bronchoscopy ; Diagnosis, Differential ; Endosonography ; Glucocorticoids/therapeutic use ; Humans ; Immunoglobulin G4-Related Disease/complications/*diagnosis/drug therapy/pathology ; Lung Neoplasms/*diagnosis ; Lymphadenopathy/diagnosis/etiology/pathology ; Male ; Mesothelioma/*diagnosis ; Mesothelioma, Malignant ; Pleural Diseases/complications/*diagnosis/drug therapy/pathology ; Pleural Effusion/etiology ; Pleural Neoplasms/*diagnosis ; Positron Emission Tomography Computed Tomography ; Prednisone/therapeutic use ; }, abstract = {We report a rare case of a IgG4-related disease presenting with recurrent pleural effusion, pleural thickness and multiple mediastinal lymphadenopathies and no involvement of other extrathoracic organs. A 65-year-old man with a previous asbestos exposure presented with cough and pain discomfort. A large right pleural effusion was detected and evacuated (siero-haematic liquid). With the suspicious of a pleural mesothelioma, a CT-scan before and a [18F]-FDG PET/CT-scan later were performed revealing multiple pleural thickenings and multiple mediastinal lymphadenopathies with radiotracer uptake. EBUS-TBNA EBUS-TBNA did not result in a formal pathological diagnosis; thus, multiple pleural biopsy were performed via right thoracoscopy. At pathology the pleura was markedly thickened by a chronic fibroinflammatory process with scattered lymphoid follicles and a large number of mature plasma cells. Immunohistochemistry shows a mixed B (CD20+) and T (CD3+) population of lymphocytes, without light chain restriction and an increased number of IgG4-positive plasma cells. A presumptive diagnosis of IgG4-related disease was formulated. Total body CT-scan excluded other organ involvement. Blood test showed elevated serum IgG4 concentrations (253 mg/dL) and mild elevation of acute-phase reactants (C-reactive protein 10.7 mg/L). Autoimmune profile was negative. A diagnosis of definite IgG4-related disease was made, and treatment with prednisone 50 mg/day was started.}, } @article {pmid30937282, year = {2019}, author = {Haygarth, M and Zaw, KK and Yachmenikova, V and Pokorny, AMJ and Kwong, KK and Heraganahally, SS}, title = {Bilateral diffuse pulmonary infiltrates secondary to malignant peritoneal mesothelioma - A rare clinical presentation.}, journal = {Respiratory medicine case reports}, volume = {26}, number = {}, pages = {326-327}, pmid = {30937282}, issn = {2213-0071}, abstract = {Diffuse pulmonary metastasis secondary to primary peritoneal malignant mesothelioma is rarely reported in the literature. In this report we describe a 59-year-old Caucasian women with no known previous asbestos exposure presenting with bilateral diffuse pulmonary opacities in association with primary malignant peritoneal mesothelioma. The diagnosis was confirmed by ultrasound guided abdominal and bronchoscopy, trans-bronchial lung biopsy. The biopsy demonstrated positive staining with AE1/3, CK7, CK5/6, WT1, calretinin and D2 40. The cells were negative for BerEP4, PAX8, CA125, ER, CD34, ERG, P63, P40, Melan A, Gata3 and mammaglobin. The morphology and immunohistochemical profile supported a diagnosis of epithelioid malignant mesothelioma.}, } @article {pmid30936339, year = {2019}, author = {Muralidhar, V and Raghav, P and Das, P and Goel, A}, title = {A case from India of pleural malignant mesothelioma probably due to domestic and environmental asbestos exposure: a posthumous report.}, journal = {BMJ case reports}, volume = {12}, number = {3}, pages = {}, pmid = {30936339}, issn = {1757-790X}, mesh = {Adult ; Air Pollutants, Occupational/*adverse effects ; Asbestos/*adverse effects ; Compensation and Redress/legislation & jurisprudence ; Environmental Exposure/*adverse effects/legislation & jurisprudence ; Fatal Outcome ; Humans ; India ; Lung Neoplasms/chemically induced/*diagnosis/mortality ; Male ; Mesothelioma/chemically induced/*diagnosis/mortality ; Mesothelioma, Malignant ; Occupational Exposure/*adverse effects/legislation & jurisprudence ; Pleural Neoplasms/chemically induced/*diagnosis/mortality ; Workers' Compensation/legislation & jurisprudence ; }, abstract = {India is the largest consumer of asbestos in the world. There is no report from India of mesothelioma related to asbestos. The case is a 42-year-old man who died of pleural mesothelioma. He was exposed to asbestos domestically and from the environment since birth. Two of his close family members worked in a factory that used asbestos. The living quarter of the family was within the premises of the factory. Asbestos waste was strewn on the grounds surrounding the quarters. After decades of legal battles by workers and families exposed to asbestos, Indian courts have ordered remedial measures and compensation to people, who are exposed to asbestos at work and the environment. Mesothelioma, currently in epidemic proportions in the west where asbestos production was banned in the 1990s, could rise to alarming levels in the next decades in India if the legal remedial measures are not implemented soon.}, } @article {pmid30928905, year = {2019}, author = {Reid, A and Franklin, P and Berry, G and Peters, S and Sodhi-Berry, N and Brims, F and Musk, AW and de Klerk, NH}, title = {Response to letter by Farioli et al.}, journal = {Occupational and environmental medicine}, volume = {76}, number = {5}, pages = {356}, doi = {10.1136/oemed-2019-105740}, pmid = {30928905}, issn = {1470-7926}, mesh = {Adult ; Asbestos, Crocidolite ; Child ; Humans ; *Lung Neoplasms ; *Mesothelioma ; }, } @article {pmid30927363, year = {2019}, author = {Koutros, S and Lubin, JH and Graubard, BI and Blair, A and Stewart, PA and Beane Freeman, LE and Silverman, DT}, title = {Extended Mortality Follow-up of a Cohort of 25,460 Workers Exposed to Acrylonitrile.}, journal = {American journal of epidemiology}, volume = {188}, number = {8}, pages = {1484-1492}, pmid = {30927363}, issn = {1476-6256}, support = {Z01 CP010120/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Acrylonitrile/*toxicity ; Aged ; Aged, 80 and over ; Cause of Death ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/mortality ; Male ; Middle Aged ; Mortality/*trends ; Occupational Diseases/*mortality ; Occupational Exposure/*adverse effects ; United States/epidemiology ; }, abstract = {We extended the mortality follow-up of a cohort of 25,460 workers employed at 8 acrylonitrile (AN)-producing facilities in the United States by 21 years. Using 8,124 deaths and 1,023,922 person-years of follow-up, we evaluated the relationship between occupational AN exposure and death. Standardized mortality ratios (SMRs) based on deaths through December 31, 2011, were calculated. Work histories and monitoring data were used to develop quantitative estimates of AN exposure. Hazard ratios were estimated by Cox proportional hazards regression. All-cause mortality and death from total cancer were less than expected compared with the US population. We observed an excess of death due to mesothelioma (SMR = 2.24, 95% confidence interval (CI): 1.39, 3.42); no other SMRs were elevated overall. Cox regression analyses revealed an elevated risk of lung and bronchial cancer (n = 808 deaths; for >12.1 ppm-year vs. unexposed, hazard ratio (HR) = 1.43, 95% CI: 1.13, 1.81; P for trend = 0.05), lagged 10 years, that was robust in sensitivity analyses adjusted for smoking and co-exposures including asbestos. Death resulting from bladder cancer (for >2.56 ppm vs. unexposed, lagged 10-year HR = 2.96, 95% CI: 1.38, 6.34; P for trend = 0.02) and pneumonitis (for >3.12 ppm-year vs. unexposed, HR = 4.73, 95% CI: 1.42, 15.76; P for trend = 0.007) was also associated with AN exposure. We provide additional evidence of an association between AN exposure and lung cancer, as well as possible increased risk for death due to bladder cancer and pneumonitis.}, } @article {pmid30927189, year = {2019}, author = {Kennedy, JM}, title = {The forensic significance of pseudomesotheliomatous adenocarcinoma of the lung.}, journal = {Forensic science, medicine, and pathology}, volume = {15}, number = {3}, pages = {458-462}, pmid = {30927189}, issn = {1556-2891}, mesh = {Adenocarcinoma/metabolism/*pathology ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; Lung/*pathology ; Lung Neoplasms/metabolism/*pathology ; Mesothelioma ; Mesothelioma, Malignant ; }, abstract = {Pseudomesotheliomatous carcinomas (PMC) are rare tumors that clinically, macroscopically, and sometimes histologically resemble malignant pleural mesotheliomas. We report a case of a 91 year woman who was found to have diffuse nodular pleural thickening and a lung mass during a workup for persistent cough. She declined rapidly and died before a histologic diagnosis could be made. Postmortem examination revealed a tumor that diffusely involved the pleural surface with local extension into the chest wall, pericardium, and diaphragm along with a concurrent lung mass. Histologic examination showed poorly-differentiated cells predominantly arranged in sheets, cords, and nests with focal glandular differentiation. An immunohistochemical panel of calretinin, WT1, BEREP4, MOC31, and TTF1 confirmed the diagnosis of primary lung adenocarcinoma. The macroscopic, histologic, and immunohistochemical features used to distinguish metastatic and primary lung adenocarcinoma from epithelioid malignant mesothelioma are discussed. The distinction of malignant mesothelioma from pseudomesotheliomatous carcinoma is important for medicolegal reasons regarding asbestos related compensation claims.}, } @article {pmid30924615, year = {2019}, author = {Algranti, E and Ramos-Bonilla, JP and Terracini, B and Santana, VS and Comba, P and Pasetto, R and Mazzeo, A and Cavariani, F and Trotta, A and Marsili, D}, title = {Prevention of Asbestos Exposure in Latin America within a Global Public Health Perspective.}, journal = {Annals of global health}, volume = {85}, number = {1}, pages = {}, pmid = {30924615}, issn = {2214-9996}, mesh = {Asbestos, Serpentine/*economics/*toxicity ; Carcinogenesis ; Environmental Exposure/adverse effects/analysis/prevention & control ; Humans ; Latin America/epidemiology ; Lung Neoplasms/*epidemiology/*etiology ; Mesothelioma/*epidemiology ; Mining ; Occupational Exposure/adverse effects/analysis/*prevention & control ; Public Health ; }, abstract = {BACKGROUND: Asbestos consumption in Latin America (LA) amounts to 10% of yearly global production. Little is known about the impact of asbestos exposure in the region.

OBJECTIVE: To discuss scientific and socio-economic issues and conflicts of interest and to summarize epidemiological data of asbestos health effects in LA.

DISCUSSION: Recent data on chrysotile strengthened the evidence of its carcinogenicity and showed an excessive risk of lung cancer at cumulative exposure levels as low as 1.5 fibre-years/ml. Technology for substitution is available for all asbestos-containing products and ceasing asbestos production and manufacturing will not result in unemployment and loss of income, except for the mining industry. The flawed arguments used by the industry to maintain its market, both to the public and in courtrooms, strongly relies on the lack of local evidence of the ill effects and on the invisibility of asbestos-related diseases in LA, due to the limited number of studies and the exposed workers' difficulty accessing health services. The few epidemiological studies available show clear evidence of clusters of mesothelioma in municipalities with a history of asbestos consumption and a forecasted rise in its incidence in Argentina and Brazil for the next decade. In Brazil, non-governmental organizations of asbestos workers were pivotal to counterbalance misinformation and inequities, ending recently in a Supreme Court decision backing an asbestos ban. In parallel, continuous efforts should be made to stimulate the growth of competent and ethical researchers to convey adequate information to the scientific community and to the general public.}, } @article {pmid30917938, year = {2019}, author = {Linton, A and Blinman, P and Kao, S and van Zandwijk, N}, title = {Patterns of care and survival of older patients with malignant pleural mesothelioma.}, journal = {Journal of geriatric oncology}, volume = {10}, number = {4}, pages = {573-576}, doi = {10.1016/j.jgo.2019.02.013}, pmid = {30917938}, issn = {1879-4076}, mesh = {Aged ; Aged, 80 and over ; Antineoplastic Agents/*therapeutic use ; Female ; Humans ; Kaplan-Meier Estimate ; Lung Neoplasms/mortality/*therapy ; Male ; Mesothelioma/mortality/*therapy ; Mesothelioma, Malignant ; New South Wales ; Palliative Care/*statistics & numerical data ; Pleural Neoplasms/mortality/*therapy ; Pneumonectomy/*statistics & numerical data ; Radiotherapy/*statistics & numerical data ; Radiotherapy, Adjuvant ; Survival Rate ; Thoracic Surgical Procedures/statistics & numerical data ; }, abstract = {OBJECTIVE: Malignant pleural mesothelioma (MPM) is a cancer that primarily affects older adults. However this patient population is frequently under-represented in clinical studies. Therefore, we studied the impact of advancing age on treatment utilisation and clinical outcomes in an extensive series of minimally selected MPM patients.

MATERIALS AND METHODS: Patients with MPM receiving compensation from the New South Wales (NSW) Dust Diseases Authority (2002-2009) were assessed. They were categorised by age (<70 years, 70-80 years or > 80 years) and chi-square testing was used to assess the relationship between clinical and demographic variables, age, treatment and overall survival (OS).

RESULTS: We identified 910 patients; 41% were aged <70 years, 40% were aged 70-80 years, and 19% were aged >80 years old. Median OS decreased with increasing age: 13.5 months in <70 years, 9.5 months in 70-80 years and 7.1 months in >80 years as did chemotherapy use (66%, 35% and 8% respectively). Radical surgical intervention, adjuvant, and palliative radiotherapy were less frequently used with advanced age. A Kaplan Meier analysis revealed that there was a significant survival advantage (p < .001) for patients <70 and 70-80 years receiving chemotherapy (16.8 vs 7.0 months; 13.9 vs 5.8 months respectively), but not for patients >80 years.

CONCLUSION: Advancing age group of NSW patients with MPM was associated with reduced treatment utilisation and a decline in OS. Prospective studies are warranted to verify if current treatment guidelines are relevant for the older adults with MPM.}, } @article {pmid30915902, year = {2019}, author = {Grosso, F and Croce, A and Libener, R and Mariani, N and Pastormerlo, M and Maconi, A and Rinaudo, C}, title = {Asbestos fiber identification in liver from cholangiocarcinoma patients living in an asbestos polluted area: a preliminary study.}, journal = {Tumori}, volume = {105}, number = {5}, pages = {404-410}, doi = {10.1177/0300891619839305}, pmid = {30915902}, issn = {2038-2529}, mesh = {Asbestos/isolation & purification/*toxicity ; Bile Duct Neoplasms/chemically induced/*diagnostic imaging/pathology ; Cholangiocarcinoma/chemically induced/*diagnostic imaging/pathology ; Environmental Pollutants/isolation & purification/toxicity ; Female ; Humans ; Italy ; Liver/*diagnostic imaging/drug effects/pathology ; Male ; Mesothelioma/chemically induced ; Microscopy, Electron, Scanning ; Occupational Exposure ; }, abstract = {PURPOSE: To assess whether asbestos fibers may be observed in liver tissue of patients with cholangiocarcinoma (CC) with environmental or working asbestos exposure.

METHODS: Detection of fibers was performed directly on histologic sections of liver from 7 patients with CC using optical microscope and variable pressure scanning electron microscopy equipped with energy-dispersive spectroscopy (VP-SEM/EDS). All patients were from Casale Monferrato, Italy, a highly asbestos-polluted town. Due to ethical constraints, observers were blinded to patients' clinical features.

RESULTS: Fibers/bundles of fibers of chrysotile were detected in 5 out of 7 patients (71%). The boundary between healthy and neoplastic tissue or the fibrocollagen tissue produced by the neoplasia were identified as areas of fiber incorporation.

CONCLUSIONS: This study is the first report about the detection of chrysotile asbestos fibers in the liver of patients with CC. Further studies on larger cohorts are needed to corroborate our preliminary findings.}, } @article {pmid30915265, year = {2019}, author = {Robalino Gonzaga, ES and Guzman Rojas, P and Vanar, V}, title = {Malignant Peritoneal Mesothelioma Mimicking Recurrent Diverticulitis.}, journal = {Cureus}, volume = {11}, number = {1}, pages = {e3906}, pmid = {30915265}, issn = {2168-8184}, abstract = {Mesothelioma is an uncommon type of cancer arising from the mesothelial cells that form the lining of several cavities in the body. Exposure to asbestos is the leading known cause of mesothelioma. We present a 73-year-old male with a significant asbestos exposure and a recent history of recurrent diverticulitis who reported persistent left lower quadrant (LLQ) pain despite several courses of empiric antibiotic therapy. A recent computed tomography (CT) performed due to nonresolving symptoms showed possible nodularity of the mesentery and subsequent positron emission tomography (PET) scan demonstrated multiple hypermetabolic mesenteric lesions, notably in the left paracolic gutter. A colonoscopy was subsequently performed which demonstrated severe diverticulosis, but no obvious luminal lesions. The patient underwent an exploratory laparoscopy showing extensive peritoneal carcinomatosis involving all mesenteric surfaces and partial involvement of the right diaphragm. Final pathology revealed malignant epithelial mesothelioma with peritoneal seeding. The patient was referred to oncology and was started on hyperthermic intraperitoneal chemotherapy (HIPEC) and cytoreductive surgery (CRS). Our case highlights a challenging presentation of malignant peritoneal mesothelioma (MPM), which is often initially misdiagnosed due to vague symptoms. Physicians should consider further diagnostic workup for unrelenting LLQ abdominal pain after diverticulitis has been treated.}, } @article {pmid30900641, year = {2019}, author = {Punatar, CB and Jadhav, KK and Kumar, V and Sagade, SN}, title = {Malignant mesothelioma of tunica vaginalis without any risk factors: An uncommon case.}, journal = {Journal of cancer research and therapeutics}, volume = {15}, number = {Supplement}, pages = {S167-S169}, doi = {10.4103/jcrt.JCRT_1403_16}, pmid = {30900641}, issn = {1998-4138}, mesh = {Adult ; Humans ; Lung Neoplasms/*diagnosis/pathology/surgery ; Male ; Mesothelioma/*diagnosis/pathology/surgery ; Mesothelioma, Malignant ; Orchiectomy ; Positron Emission Tomography Computed Tomography ; Scrotum/diagnostic imaging/*pathology/surgery ; Testicular Neoplasms/*diagnosis/pathology/surgery ; Testis/diagnostic imaging/*pathology/surgery ; Treatment Outcome ; Ultrasonography ; }, abstract = {Malignant mesothelioma (MM) of the tunica vaginalis (TV) is a rare tumor. It is seen in elderly patients, with painless scrotal swelling being the most common presentation. The exact etiology is unknown; a few risk factors have been suggested. Here, we present an uncommon case of MM of TV without any known predisposing factors. We also discuss the possible risk factors, clinical presentation, pathological features and the difficulties in diagnosis, and management of this rare malignancy.}, } @article {pmid30893058, year = {2019}, author = {Levpuscek, K and Goricar, K and Kovac, V and Dolzan, V and Franko, A}, title = {The influence of genetic variability of DNA repair mechanisms on the risk of malignant mesothelioma.}, journal = {Radiology and oncology}, volume = {53}, number = {2}, pages = {206-212}, pmid = {30893058}, issn = {1581-3207}, mesh = {Aged ; Asbestos/toxicity ; Carcinogens/toxicity ; Case-Control Studies ; *DNA Repair ; DNA-Binding Proteins/*genetics ; Endonucleases/*genetics ; Female ; *Genetic Variation ; Humans ; Lung Neoplasms/etiology/*genetics ; Male ; Mesothelioma/etiology/*genetics ; Mesothelioma, Malignant ; Middle Aged ; *Polymorphism, Genetic ; Retrospective Studies ; Risk ; X-ray Repair Cross Complementing Protein 1/*genetics ; }, abstract = {Background Malignant mesothelioma (MM) is a rare aggressive tumour of mesothelium caused by asbestos exposure. It has been suggested that the genetic variability of proteins involved in DNA repair mechanisms affects the risk of MM. This study investigated the influence of functional polymorphisms in ERCC1 and XRCC1 genes, the interactions between these polymorphisms as well as the interactions between these polymorphisms and asbestos exposure on MM risk. Patients and methods In total, 237 cases with MM and 193 controls with no asbestos-related disease were genotyped for ERCC1 and XRCC1 polymorphisms. Results ERCC1 rs3212986 polymorphism was significantly associated with a decreased risk of MM (odds ratio [OR] = 0.61; 95% confidence interval [CI] = 0.41-0.91; p = 0.014). No associations were observed between other genetic polymorphisms and MM risk. Interactions between polymorphisms did not significantly influence MM risk. Interaction between ERCC1 rs11615 and asbestos exposure significantly influenced MM risk (OR = 3.61; 95% CI = 1.12-11.66; p = 0.032). Carriers of polymorphic ERCC1 rs11615 allele who were exposed to low level of asbestos had a decreased risk of MM (OR = 0.40; 95% CI = 0.19-0.84; p = 0.016). Interactions between other polymorphisms and asbestos exposure did not significantly influence MM risk. Conclusions Our findings suggest that the genetic variability of DNA repair mechanisms could contribute to the risk of developing MM.}, } @article {pmid30892588, year = {2019}, author = {Dragani, TA and Colombo, F and Pavlisko, EN and Roggli, VL}, title = {Corrigendum: Malignant mesothelioma diagnosed at a younger age is associated with heavier asbestos exposure.}, journal = {Carcinogenesis}, volume = {40}, number = {3}, pages = {492}, doi = {10.1093/carcin/bgz037}, pmid = {30892588}, issn = {1460-2180}, } @article {pmid30891101, year = {2019}, author = {Wang, Y and Jiang, Z and Yan, J and Ying, S}, title = {HMGB1 as a Potential Biomarker and Therapeutic Target for Malignant Mesothelioma.}, journal = {Disease markers}, volume = {2019}, number = {}, pages = {4183157}, pmid = {30891101}, issn = {1875-8630}, mesh = {Animals ; Biomarkers, Tumor/*genetics/metabolism ; Gene Expression Regulation, Neoplastic ; HMGB1 Protein/*genetics/metabolism ; Humans ; Lung Neoplasms/drug therapy/*genetics/metabolism/pathology ; Mesothelioma/drug therapy/*genetics/metabolism/pathology ; Mesothelioma, Malignant ; }, abstract = {Malignant mesothelioma (MM) is a rare, aggressive, and highly lethal cancer that is substantially induced by exposure to asbestos fibers. High-mobility group box 1 (HMGB1) is an intriguing proinflammatory molecule involved in MM. In this review, we describe the possible crucial roles of HMGB1 in carcinogenic mechanisms based on in vivo and in vitro experimental evidence and outline the clinical findings of epidemiological investigations regarding the possible roles of HMGB1 as a biomarker for MM. We conclude that novel strategies targeting HMGB1 may suppress MM cells and interfere with asbestos-induced inflammation.}, } @article {pmid30888083, year = {2019}, author = {Hino, O and Abe, M and Han, B and Yan, Y}, title = {In commemoration of the 2018 Mataro Nagayo Prize: A road to early diagnosis and monitoring of asbestos-related mesothelioma.}, journal = {Cancer science}, volume = {110}, number = {5}, pages = {1518-1524}, pmid = {30888083}, issn = {1349-7006}, support = {S1311011//Foundation of Strategic Research Projects in Private Universities of the NEXT (Ministry of Education, Culture, Sports, Science and Technology of Japan)/ ; S1511008L//Foundation of Strategic Research Projects in Private Universities of the NEXT (Ministry of Education, Culture, Sports, Science and Technology of Japan)/ ; //Institute for Environmental and Gender-Specific Medicine of Juntendo University Urayasu Hospital/ ; //Shizuoka Medical Research Center for Disaster of Juntendo University Shizuoka Hospital/ ; 221S0001//Ministry of Education, Culture, Sports, Science and Technology of Japan/ ; }, mesh = {Animals ; Asbestos/*adverse effects ; Awards and Prizes ; Biomarkers, Tumor/blood ; Disease Management ; Early Detection of Cancer/*methods ; Humans ; Japan ; Lung Neoplasms/blood/chemically induced/*diagnosis/*surgery ; Mesothelin ; Mesothelioma/blood/chemically induced/*diagnosis/*surgery ; Mesothelioma, Malignant ; Occupational Diseases/chemically induced/diagnosis/surgery ; Oncogene Proteins/*blood ; }, abstract = {Primarily caused by exposure to asbestos, mesothelioma is a typical occupational disease. The latency of mesothelioma is as long as 20-40 years, and the cancer initially progresses mainly along the surfaces of pleura or peritoneum without forming masses. As symptoms do not develop until late stages, it has been challenging to diagnose this disease in its early stages and to carry out complete surgical removal. In responding to Japan's asbestos crisis in the mid-2000s, we have developed and improved ERC/MSLN-based serum and radiological markers and pioneered the use of an N-ERC ELISA kit for screening populations at risk for asbestos exposure. In the present article, we review our research toward early diagnosis of asbestos-related mesothelioma before symptoms develop and share our clinical experience of screening, diagnosing and monitoring of this disease. This paper is dedicated to the author (Dr Okio Hino) to commemorate the honor bestowed upon him as the recipient of the Mataro Nagayo Prize in 2018.}, } @article {pmid30886321, year = {2019}, author = {Jeffery, E and Lee, YCG and Newton, RU and Lyons-Wall, P and McVeigh, J and Nowak, AK and Cheah, HM and Nguyen, B and Fitzgerald, DB and Creaney, J and Straker, L and Peddle-McIntyre, CJ}, title = {Body composition and nutritional status in malignant pleural mesothelioma: implications for activity levels and quality of life.}, journal = {European journal of clinical nutrition}, volume = {73}, number = {10}, pages = {1412-1421}, doi = {10.1038/s41430-019-0418-9}, pmid = {30886321}, issn = {1476-5640}, mesh = {Aged ; Australia/epidemiology ; *Body Composition ; Cross-Sectional Studies ; Diet ; Exercise/*physiology ; Female ; Humans ; Lung Neoplasms/*physiopathology ; Male ; Malnutrition/epidemiology ; Mesothelioma/*physiopathology ; Mesothelioma, Malignant ; Middle Aged ; *Nutritional Status ; Pleural Neoplasms/*physiopathology ; Prospective Studies ; *Quality of Life ; Sarcopenia/epidemiology ; }, abstract = {BACKGROUND/OBJECTIVES: Malignant pleural mesothelioma (MPM) is an incurable cancer and optimizing daily physical activity and quality of life are key goals of patient management. Little is known about the prevalence of pre-sarcopenia and malnutrition in MPM or their associations with patient outcomes. This study aimed to determine the prevalence of pre-sarcopenia and malnutrition in MPM and investigate if activity levels and quality of life differed according to body composition and nutritional status.

SUBJECTS/METHODS: Patients with a diagnosis of MPM were recruited. Pre-sarcopenia was defined as low appendicular skeletal muscle mass (≤ 7.26 kg/m[2] for men and ≤ 5.45 kg/m[2] for women), measured by dual energy X-ray absorptiometry. Malnutrition was defined as a rating of B or C on the Patient-Generated Subjective Global Assessment. Outcome measures included objective activity levels (Actigraph GT3X) and health-related quality of life (HRQoL; Functional Assessment of Cancer Therapy General).

RESULTS: Sixty-one people participated (79% male, median age 69 [IQR 62-74] years and median BMI 25.8 [IQR 24.3-28.4] kg/m[2]). Fifty-four percent were pre-sarcopenic and 38% were malnourished. Percent of time spent in light activity/day was lower in participants with pre-sarcopenia compared with non-sarcopenic participants (median 25.4 [IQR 19.8-32.1]% vs. 32.3 [27.1-35.6]%; p = 0.008). Participants with malnutrition had poorer HRQoL than well-nourished participants (mean 69.0 (16.3) vs. 84.4 (13.3); p < 0.001).

CONCLUSION: Participants with MPM had high rates of pre-sarcopenia and malnutrition. Pre-sarcopenia was associated with poorer activity levels, whilst malnutrition was associated with poorer quality of life. Interventions that aim to address reduced muscle mass and weight loss, should be tested in MPM to assess their impact on patient outcomes.}, } @article {pmid30885349, year = {2019}, author = {Ahmadzada, T and Lee, K and Clarke, C and Cooper, WA and Linton, A and McCaughan, B and Asher, R and Clarke, S and Reid, G and Kao, S}, title = {High BIN1 expression has a favorable prognosis in malignant pleural mesothelioma and is associated with tumor infiltrating lymphocytes.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {130}, number = {}, pages = {35-41}, doi = {10.1016/j.lungcan.2019.02.005}, pmid = {30885349}, issn = {1872-8332}, mesh = {Adaptor Proteins, Signal Transducing/genetics/*metabolism ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics/*metabolism ; Lung Neoplasms/*genetics/immunology/mortality ; Lymphocytes, Tumor-Infiltrating/*immunology ; Male ; Mesothelioma/*genetics/immunology/mortality ; Mesothelioma, Malignant ; Middle Aged ; Nuclear Proteins/genetics/*metabolism ; Pleural Neoplasms/*genetics/immunology/mortality ; Prognosis ; Survival Analysis ; Tumor Suppressor Proteins/genetics/*metabolism ; Up-Regulation ; }, abstract = {OBJECTIVES: A number of key immune regulators show prognostic value in malignant pleural mesothelioma (MPM), but the association between Bridging integrator 1 (BIN1), indoleamine 2,3 dioxygenase 1 (IDO1) and patient outcome has not been investigated. We aimed to determine the expression of BIN1 and IDO1, their association with other markers and impact on overall survival (OS) in MPM.

MATERIALS AND METHODS: The expression of BIN1, IDO1, CD3, CD20 and CD68 were evaluated by immunohistochemistry in 67 patients who underwent pleurectomy/decortication. Survival analyses were performed using the Kaplan Meier method and significant biomarkers were entered into a Cox Regression multivariate model, accounting for known prognostic factors such as age, gender, histological subtype, PD-L1 expression and neutrophil-to-lymphocyte ratio.

RESULTS: Immune markers were variably expressed in tumor cells, ranging from 0% to 100% for BIN1 (median: 89%), and 0% to 77.5% for IDO1 (median: 0%). Expression of markers of tumor-infiltrating lymphocytes (TILs) and macrophages ranged from 0% to more than 50%. BIN1 expression was high in 35 patients (51%) and was associated with increased OS (median: 12 vs 6 months for high and low BIN1 respectively,p = 0.03). Multivariate analysis showed BIN1 remained an independent prognostic indicator (HR 0.39; 95% CI: 0.18-0.82, p = 0.01). The majority of patients had immune inflamed tumors (77%) and there was a significant association between TILs and BIN1 (p = 0 < 0.01), PD-L1 (p=0.04) and CD68+ macrophages in the tumor (p < 0.01). There were no significant associations between PD-L1 and BIN1 or IDO1.

CONCLUSION: High BIN1 expression is a favorable prognostic biomarker and is associated with TILs in MPM.}, } @article {pmid30882147, year = {2019}, author = {Nakai, T and Matsumoto, Y and Sasada, S and Tanaka, M and Tsuchida, T and Ohe, Y and Motoi, N}, title = {Cryobiopsy during flex-rigid pleuroscopy: an emerging alternative biopsy method in malignant pleural mesothelioma. A comparative study of pathology.}, journal = {Japanese journal of clinical oncology}, volume = {49}, number = {6}, pages = {559-566}, doi = {10.1093/jjco/hyz032}, pmid = {30882147}, issn = {1465-3621}, mesh = {Aged ; Biopsy/instrumentation/methods ; Female ; Humans ; Lung Neoplasms/*diagnosis ; Male ; Mesothelioma/*diagnosis ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/*diagnosis ; Thoracoscopy/*instrumentation/*methods ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is rarely an asbestos-related cancer with a poor prognosis that is difficult to distinguish from some benign conditions by using conventional biopsy techniques. The purpose of this study was to evaluate the utility of a novel biopsy technique using a cryoprobe during flex-rigid pleuroscopy for diagnosing MPM.

METHODS: Consecutive patients who underwent pleural cryobiopsy during flex-rigid pleuroscopy from June through November 2017 to diagnose the cause of pleural effusion were collected. From these, cases ultimately diagnosed as MPM were selected. Pleural biopsies were performed by using conventional instruments followed by a cryoprobe. The obtained samples were histologically examined and compared with regard to the quality (sample size, tissue depth, and crush rate), immunohistochemical (IHC) staining, and p16 by fluorescence in situ hybridization (FISH).

RESULTS: In total, five patients ultimately diagnosed as MPM were enrolled. The sample collected was significantly larger for cryobiopsy than conventional biopsy (18.9 mm2 vs. 6.7 mm2, P < 0.001). Full-thickness biopsies were achieved in four cases by using cryobiopsy compared with one case by conventional biopsy. Moreover, the crush rate was significantly less for cryobiopsy than conventional biopsy (9% vs. 35%, P < 0.001). The results of IHC staining and p16 by FISH were similar between biopsy techniques. Cryobiopsy successfully led to accurate diagnosis of MPM in all cases, whereas conventional biopsy was diagnostic in one case. No severe complications developed after either biopsy technique.

CONCLUSION: Cryobiopsy during flex-rigid pleuroscopy is a feasible and convenient biopsy technique that supports precise diagnosis of MPM.}, } @article {pmid30879467, year = {2019}, author = {Miyata, T and Fujiwara, Y and Nishijima, K and Futagami, F and Nakamura, T and Takamura, H}, title = {Localized multiple malignant epithelioid peritoneal mesotheliomas arising from the hepatoduodenal ligament and diaphragm: a case report.}, journal = {Journal of medical case reports}, volume = {13}, number = {1}, pages = {66}, pmid = {30879467}, issn = {1752-1947}, mesh = {Female ; Humans ; Liver Neoplasms/diagnostic imaging/*pathology/secondary/surgery ; Lung Neoplasms/diagnostic imaging/*pathology/surgery ; Mesothelioma/diagnostic imaging/*pathology/surgery ; Mesothelioma, Malignant ; Middle Aged ; Muscle Neoplasms/*pathology ; Neoplasm Invasiveness ; Peritoneal Neoplasms/diagnostic imaging/*pathology/secondary/surgery ; Tomography, X-Ray Computed ; }, abstract = {BACKGROUND: Malignant peritoneal mesothelioma is a rare aggressive tumor of the peritoneum. We report a rare case of resection of multiple localized malignant peritoneal mesotheliomas.

CASE PRESENTATION: A 55-year-old Japanese woman was admitted to our hospital because liver tumors were detected by abdominal ultrasonography during a screening examination. Blood examination findings, including tumor makers, were within normal ranges. She had no evidence of exposure to asbestos. Computed tomography showed four hypervascular, round liver tumors, one in the lateral liver segment adjacent to the hepatic hilus, and the other three on the liver surface. Computed tomography angiography revealed that the tumor in the lateral segment had strong enhancement and was fed from the left gastric artery. In contrast, the other tumors showed no enhancement, and were fed from the right inferior phrenic artery. Abnormal accumulation was identified in the four tumors only with [18]F-fluorodeoxyglucose positron emission tomography. It was very difficult to obtain a definitive preoperative diagnosis, but surgical resection was performed because we considered potential malignancy. Laparotomy revealed the principal site of the tumor in the lateral segment was on the hepatoduodenal ligament, and all other tumors were on the diaphragm. A left lobectomy and partial diaphragmatic resection were performed. The final pathological diagnosis was multiple malignant epithelioid mesotheliomas. Our patient has had no recurrence for 20 months postoperatively.

CONCLUSIONS: In general, malignant peritoneal mesotheliomas are classified as diffuse tumors, which are often unresectable and have a poor prognosis. However, early diagnosis and treatment, particularly with the localized type, as in our patient, could lead to long-term survival of the patient. We recommend that multiple malignant epithelioid mesotheliomas be included in the differential diagnosis for patients with subcapsular hepatic tumors.}, } @article {pmid30874891, year = {2019}, author = {Hutter, HP and Waldhoer, T and Müller, K and Hackl, M and Weitensfelder, L and Heinzl, H}, title = {Cancer incidence in an Austrian alpine valley 1983-2012 : A descriptive study.}, journal = {Wiener klinische Wochenschrift}, volume = {131}, number = {9-10}, pages = {200-204}, pmid = {30874891}, issn = {1613-7671}, mesh = {Asbestos/adverse effects ; Austria/epidemiology ; Hexachlorobenzene/*adverse effects ; Humans ; Incidence ; Lung Neoplasms/epidemiology ; Mesothelioma/epidemiology ; Neoplasms/*epidemiology ; }, abstract = {After one of Austria's largest environmental scandals in 2014, which involved the release of hexachlorobenzene (HCB) in the Carinthian valley Görtschitztal, concerns about increased cancer rates have arísen in the affected local population. A descriptive study was conducted to examine the cancer incidence rates between 1983 and 2012. Data from the affected area (Görtschitztal, district St. Veit) were compared to data from the neighboring area within the same district and Carinthia excluding St. Veit, considering incidence rates of liver, lung, kidney, thyroid cancer and mesothelioma. Prostate cancer and carcinoma in situ were both included and excluded from overall cancer incidents in order to prevent potential bias due to screening programs. Considering the observed variability at an overall level, no conspicuous differences in cancer incidences could be found (Carinthia: 495, St. Veit West: 408, St. Veit East: 572 cases per 100,000 person-years in 2012). For some cancer types, e. g. liver, thyroid cancer and mesothelioma, the affected region showed a higher increase in rates than the neighboring area or Carinthia overall; however, these increased rates date back to a time prior to the HCB exposure, suggesting other carcinogenic influences, such as asbestos exposure from antecedent years.}, } @article {pmid30873891, year = {2019}, author = {Poland, CA and Duffin, R}, title = {The toxicology of chrysotile-containing brake debris: implications for mesothelioma.}, journal = {Critical reviews in toxicology}, volume = {49}, number = {1}, pages = {11-35}, doi = {10.1080/10408444.2019.1568385}, pmid = {30873891}, issn = {1547-6898}, mesh = {Asbestos, Serpentine/*toxicity ; *Automobiles ; *Environmental Exposure ; Humans ; Mesothelioma/chemically induced/*epidemiology ; }, abstract = {The global use of "asbestos" in various commercial products has led to a wide range and pervasive legacy of disease. One such use of chrysotile asbestos was brake pads and was utilized commonly in automobiles and heavy vehicles. The result of incorporation of chrysotile into brake pads is associated with the exposure of mechanics fitting and servicing vehicles to liberated chrysotile fibers. Despite the proven exposure, the relative risk of malignant mesothelioma (MM) in this occupational population is broadly seen as low. The toxicity of particulates, including fibers such as chrysotile, is driven by a combination of dose and physicochemical properties. As such, it is plausible that chrysotile released from brake pads may have undergone modification, thereby altering the pathogenicity profile. The impact of high sheer stress causing shortening of long fibers, heat modification, binding of resin matrix to the fiber surface on the relative toxicity of brake debris with regards to MM is considered. It is apparent that released chrysotile can undergo significant modification, reducing the long fiber dose although not all modifications may lead to reduced toxicity.}, } @article {pmid30873867, year = {2019}, author = {Baqui, AA and Boire, NA and Baqui, TT and Etwaru, DJ}, title = {Malignant Mesothelioma of the Tunica Vaginalis Testis-A Malignancy Associated With Asbestos Exposure and Trauma: A Case Report and Literature Review.}, journal = {Journal of investigative medicine high impact case reports}, volume = {7}, number = {}, pages = {2324709619827335}, pmid = {30873867}, issn = {2324-7096}, mesh = {Asbestos/*adverse effects ; Humans ; Immunohistochemistry ; Lung Neoplasms/etiology/*pathology ; Male ; Mesothelioma/etiology/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/adverse effects ; Orchiectomy ; Testicular Hydrocele/etiology/*pathology ; Testicular Neoplasms/etiology/*pathology ; Testis/*injuries/*pathology ; }, abstract = {In this article, we report an unusual case of a malignant mesothelioma of the testis, presenting as hydrocele. The patient has a known medical history of trauma and occupational exposure to asbestos. The clinical features of this injury are discussed together with its immunohistochemistry. Surgical intervention is discussed due to the nature of this pathology.}, } @article {pmid30870398, year = {2019}, author = {Cuccaro, F and Nannavecchia, AM and Silvestri, S and Angelini, A and Coviello, V and Bisceglia, L and Magnani, C}, title = {Mortality for Mesothelioma and Lung Cancer in a Cohort of Asbestos Cement Workers in BARI (Italy): Time Related Aspects of Exposure.}, journal = {Journal of occupational and environmental medicine}, volume = {61}, number = {5}, pages = {410-416}, doi = {10.1097/JOM.0000000000001580}, pmid = {30870398}, issn = {1536-5948}, mesh = {Asbestos/*adverse effects ; *Construction Industry ; Humans ; Italy/epidemiology ; Lung Neoplasms/*mortality ; Mesothelioma/*mortality ; Occupational Exposure/*adverse effects/statistics & numerical data ; Time Factors ; }, abstract = {OBJECTIVE: In this cohort mortality study we used an exposure index to evaluate individual cumulative exposure as proxy of asbestos dose and we evaluated change in cancer mortality pattern after long time since the end of exposure.

METHODS: We calculated standardized mortality ratios (SMRs) for several causes of death stratified by latency, cumulative exposure, and time since last exposure (TSLE).

RESULTS: Latency: we observed a peak and then a decrease in SMR for lung, pleural, and peritoneal cancer. Cumulative Exposure: We observed a peak and then a decrease in SMR for lung and pleural cancer, not for peritoneal cancer. TSLE: Pleural cancer SMR peaked at 20 to 29 years, then decreased, peritoneal cancer SMR reached a plateau after 20 years and lung cancer mortality was in excess in each class.

CONCLUSIONS: We found different patterns in mortality in the main asbestos-related tumors.}, } @article {pmid30863440, year = {2019}, author = {Liang, Y and Zheng, G and Yin, W and Song, H and Li, C and Tian, L and Yang, D}, title = {Significance of EGFR and PTEN Expression and PLR and NLR for Predicting the Prognosis of Epithelioid Malignant Peritoneal Mesothelioma.}, journal = {Gastroenterology research and practice}, volume = {2019}, number = {}, pages = {7103915}, pmid = {30863440}, issn = {1687-6121}, abstract = {OBJECTIVE: The aim of our study was to investigate the expression of EGFR and PTEN in tissues and measure the serum platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) to evaluate the prognostic factors of patients with epithelioid malignant peritoneal mesothelioma (MPeM).

METHODS: 33 patients of pathologically diagnosed epithelioid MPeM tissues were analyzed using immunohistochemistry to detect EGFR and PTEN; the PLR and NLR were determined by using a routine blood test. We analyzed the relationships of these markers to age, sex, asbestos exposure, elevated platelet count, ascites, and clinical stage.

RESULTS: EGFR and PTEN expressions were positive in 22 (66.67%) and 7 (21.21%) epithelioid MPeM patients, respectively. However, these two markers as well as PLR and NLR were not significantly associated with age, sex, asbestos exposure, elevated platelet counts, ascites, and clinical stage (P > 0.05). The correlation between EGFR and PTEN was negative (r = -0.577, P < 0.001), but the correlation between NLR and PLR was positive (r = 0.456, P = 0.008). The median survival of all patients was 6 months. In univariate analysis, PTEN (P < 0.001), PLR (P = 0.014), and NLR (P = 0.015) affected the overall survival. Multivariate analysis revealed that PTEN and PLR were validated as predictive for overall survival of epithelioid MPeM (HR = 0.070, P = 0.001, and HR = 3.379, P = 0.007, respectively).

CONCLUSION: On the basis of these results, it is suggested that PTEN and PLR are risk factors for the prognosis of epithelioid MPeM, which may be targets for selective therapies and improve the outcomes of patients with epithelioid MPeM.}, } @article {pmid30863365, year = {2019}, author = {Baird, AM and Easty, D and Jarzabek, M and Shiels, L and Soltermann, A and Klebe, S and Raeppel, S and MacDonagh, L and Wu, C and Griggs, K and Kirschner, MB and Stanfill, B and Nonaka, D and Goparaju, CM and Murer, B and Fennell, DA and O'Donnell, DM and Barr, MP and Mutti, L and Reid, G and Finn, S and Cuffe, S and Pass, HI and Opitz, I and Byrne, AT and O'Byrne, KJ and Gray, SG}, title = {When RON MET TAM in Mesothelioma: All Druggable for One, and One Drug for All?.}, journal = {Frontiers in endocrinology}, volume = {10}, number = {}, pages = {89}, pmid = {30863365}, issn = {1664-2392}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive inflammatory cancer with a poor survival rate. Treatment options are limited at best and drug resistance is common. Thus, there is an urgent need to identify novel therapeutic targets in this disease in order to improve patient outcomes and survival times. MST1R (RON) is a trans-membrane receptor tyrosine kinase (RTK), which is part of the c-MET proto-oncogene family. The only ligand recognized to bind MST1R (RON) is Macrophage Stimulating 1 (MST1), also known as Macrophage Stimulating Protein (MSP) or Hepatocyte Growth Factor-Like Protein (HGFL). In this study, we demonstrate that the MST1-MST1R (RON) signaling axis is active in MPM. Targeting this pathway with a small molecule inhibitor, LCRF-0004, resulted in decreased proliferation with a concomitant increase in apoptosis. Cell cycle progression was also affected. Recombinant MST1 treatment was unable to overcome the effect of LCRF-0004 in terms of either proliferation or apoptosis. Subsequently, the effect of an additional small molecular inhibitor, BMS-777607 (which targets MST1R (RON), MET, Tyro3, and Axl) also resulted in a decreased proliferative capacity of MPM cells. In a cohort of MPM patient samples, high positivity for total MST1R by IHC was an independent predictor of favorable prognosis. Additionally, elevated expression levels of MST1 also correlated with better survival. This study also determined the efficacy of LCRF-0004 and BMS-777607 in xenograft MPM models. Both LCRF-0004 and BMS-777607 demonstrated significant anti-tumor efficacy in vitro, however BMS-777607 was far superior to LCRF-0004. The in vivo and in vitro data generated by this study indicates that a multi-TKI, targeting the MST1R/MET/TAM signaling pathways, may provide a more effective therapeutic strategy for the treatment of MPM as opposed to targeting MST1R alone.}, } @article {pmid30859065, year = {2019}, author = {Wallen, T and Jagan, N and Krishnan, M and Depew, Z}, title = {A 75 year old male with recurrent unilateral pleural effusion and positive ANA.}, journal = {Respiratory medicine case reports}, volume = {26}, number = {}, pages = {301-303}, pmid = {30859065}, issn = {2213-0071}, abstract = {This case report describes the clinical course and diagnostic challenges arising in a 75 year old man who initially presented with progressive shortness of breath. Imaging revealed a pleural effusion, which was recurrent following thoracentesis. While his initial workup suggested an autoimmune etiology, further diagnostic testing revealed a diagnosis of malignant pleural mesothelioma. Curiously, the patient had no known asbestos exposure, which is classically associated with acquired mesothelioma. There are a small number of similar cases with a possible overlap between positive autoimmune serologies and mesothelioma; however, the underlying pathophysiology remains elusive. It is the authors' goal to contribute this case to the few cases describing such overlap syndromes.}, } @article {pmid30851279, year = {2019}, author = {Mandel, JH and Odo, NU and Alexander, BH}, title = {Potential Problems with Determining Elongate Mineral Particle (EMP) Potency (Comments on article entitled, "A Comparison of Asbestos Fiber Potency and Elongate Mineral Particle (EMP) Potency for Mesothelioma in Humans").}, journal = {Toxicology and applied pharmacology}, volume = {370}, number = {}, pages = {131-132}, doi = {10.1016/j.taap.2019.03.002}, pmid = {30851279}, issn = {1096-0333}, mesh = {*Asbestos ; Humans ; *Lung Neoplasms ; *Mesothelioma ; }, } @article {pmid30840592, year = {2019}, author = {Senk, B and Goricar, K and Kovac, V and Dolzan, V and Franko, A}, title = {Genetic polymorphisms in aquaporin 1 as risk factors for malignant mesothelioma and biomarkers of response to cisplatin treatment.}, journal = {Radiology and oncology}, volume = {53}, number = {1}, pages = {96-104}, pmid = {30840592}, issn = {1581-3207}, mesh = {Age Factors ; Aged ; Alopecia/chemically induced ; Anemia/chemically induced ; Antineoplastic Agents/adverse effects/*therapeutic use ; Aquaporin 1/*genetics ; Case-Control Studies ; Cisplatin/adverse effects/*therapeutic use ; Female ; Humans ; Leukopenia/chemically induced ; Logistic Models ; Lung Neoplasms/*drug therapy/*genetics/mortality ; Male ; Mesothelioma/*drug therapy/*genetics/mortality ; Mesothelioma, Malignant ; Middle Aged ; *Polymorphism, Single Nucleotide ; Risk Assessment ; Sex Factors ; Thrombocytopenia/chemically induced ; }, abstract = {Background Malignant mesothelioma (MM) is an asbestos related aggressive tumor with poor prognosis. The aim of this study was to investigate if aquaporin 1 (AQP1) genetic polymorphisms influence the risk of MM and the response to cisplatin based MM treatment. Patients and methods The case-control study included 231 patients with MM and a control group of 316 healthy blood donors. All subjects were genotyped for three AQP1polymorphisms (rs1049305, rs1476597 and rs28362731). Logistic and Cox regression were used in statistical analysis. Results AQP1 rs1049305 polymorphism was significantly associated with MM risk in dominant model adjusted for gender and age (OR = 0.60, 95% CI = 0.37-0.96, Padj = 0.033). This polymorphism was also significantly associated with cisplatin based treatment related anaemia (unadjusted: OR = 0.49, 95% CI = 0.27-0.90, P = 0.021; adjusted: for CRP: OR = 0.52, 95% CI = 0.27-0.99, P = 0.046), with leukopenia (OR = 2.09, 95% CI = 1.00-4.35, P = 0.049) in dominant model and with thrombocytopenia (OR = 3.06, 95% CI = 1.01-9.28, P = 0.048) and alopecia (OR = 2.92, 95% CI = 1.00-8.46, P = 0.049) in additive model. AQP1 rs28362731 was significantly associated with thrombocytopenia (unadjusted: OR = 3.73, 95% CI = 1.00-13.84, P = 0.049; adjusted for pain: OR = 4.63, 95% CI = 1.13-19.05, P = 0.034) in additive model. Conclusions AQP1 may play a role in the risk of MM. Furthermore, AQP1 genotype information could improve the prediction of MM patients at increased risk for cisplatin toxicity.}, } @article {pmid30834036, year = {2019}, author = {Abbas, H and Rodriguez, JC and Tariq, H and Niazi, M and Alemam, A and Nayudu, SK}, title = {Malignant Peritoneal Mesothelioma Without Asbestos Exposure.}, journal = {Gastroenterology research}, volume = {12}, number = {1}, pages = {48-51}, pmid = {30834036}, issn = {1918-2805}, abstract = {Malignant mesothelioma is a rare neoplasm of the serosal linings. Mesothelioma has been linked to asbestos exposure, with prior asbestos exposure linked to 33-50% of malignant peritoneal mesotheliomas. We describe a case of malignant peritoneal mesothelioma (MPM) without any prior exposure to asbestos in a 40-year-old Hispanic female who presented to the emergency department with worsening abdominal pain and distension. She had a history of beta thalassemia trait and iron deficiency anemia. Examination revealed a distended abdomen with protruding umbilicus and positive shifting dullness. Laboratory tests showed anemia. Computed tomography (CT) of the abdomen revealed massive complex ascites suspicious of a malignant process. Ascitic fluid analysis showed serum ascites albumin gradient (SAAG) of 1.1 g/dL with a total protein of 5.2 g/dL. She underwent laparoscopic peritoneal biopsy which yielded epithelioid type malignant mesothelioma. She was started on chemotherapy with cisplatin and pemetrexed. The last follow-up was 27 months after the diagnosis. MPM is a rare and life-threatening malignancy. Frequently, the symptoms are non-specific. This poses a diagnostic challenge for physicians and probably the reason why the diagnosis is often delayed, especially in the absence of risk factors.}, } @article {pmid30815702, year = {2019}, author = {Pasetto, R and Zona, A and Fazzo, L and Binazzi, A and Bruno, C and Pirastu, R and Comba, P and Marinaccio, A}, title = {Proportion of mesothelioma attributable to living in industrially contaminated areas in Italy.}, journal = {Scandinavian journal of work, environment & health}, volume = {45}, number = {5}, pages = {444-449}, doi = {10.5271/sjweh.3809}, pmid = {30815702}, issn = {1795-990X}, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Child ; Child, Preschool ; Environmental Exposure/*statistics & numerical data ; Female ; Humans ; Industry/*statistics & numerical data ; Infant ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Risk Factors ; Sex Factors ; Spatial Analysis ; Young Adult ; }, abstract = {Objectives The aim of this study was to estimate the attributable proportion (AP) of mesothelioma resulting from living in or close to major Italian industrially contaminated areas. Methods For populations living close to 39 sites of "national priority for remediation", incident mesothelioma cases were extracted from the Italian National Mesothelioma Registry (ReNaM) in the period 2000‒2011. Each site was classified in one of seven asbestos risk groups (RG) on the basis of the type of industrial plants. RG were ranked by the a priori evidence on asbestos risk. The AP for each RG was calculated as the meta-analytic estimate of AP of sites of the same group by gender and age class (0-64, 65-74, ≥75 years). The sex ratio (men/women) was computed for each RG. Results Among men, the AP by age class had the same gradient in each RG, with the highest values in the age class 0-64 years and the lowest in the ≥75 class; in the age class 0-64 years, the AP was positive in each RG, >90% in the presence of asbestos cement factories and harbors with shipyards. Among women, the overall AP decreased by RG, with negative values in the last two ranked RG; the AP by age class was variable without a definite gradient. The sex ratio was close to one only in the RG "only asbestos-cement factories"; the highest value (9.6) was observed in the age class 0-64 years in the RG "harbors with shipyard". Conclusions The integration of a geographic- and case-based approach provides valuable insights into occupational and environmental determinants of mesothelioma risk in industrially contaminated sites.}, } @article {pmid30809599, year = {2018}, author = {Biersack, B}, title = {Relations between approved platinum drugs and non-coding RNAs in mesothelioma.}, journal = {Non-coding RNA research}, volume = {3}, number = {4}, pages = {161-173}, pmid = {30809599}, issn = {2468-0540}, abstract = {Malignant mesothelioma diseases feature an increasing risk due to their severe forms and their association with asbestos exposure. Platinum(II) complexes such as cisplatin and carboplatin are clinically approved for the therapy of mesothelioma often in combination with antimetabolites such as pemetrexed or gemcitabine. It was observed that pathogenic properties of mesothelioma cells and the response of mesothelioma tumors towards platinum-based drugs are strongly influenced by non-coding RNAs, in particular, by small microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). These non-coding RNAs controlled drug sensitivity and the development of tumor resistance towards platinum drugs. An overview of the interactions between platinum drugs and non-coding RNAs is given and the influence of non-coding RNAs on platinum drug efficacy in mesothelioma is discussed. Suitable non-coding RNA-modulating agents with potentially beneficial effects on cisplatin treatment of mesothelioma diseases are mentioned. The understanding of mesothelioma diseases concerning the interactions of non-coding RNAs and platinum drugs will optimize existing therapy schemes and pave the way to new treatment options in future.}, } @article {pmid30804167, year = {2019}, author = {Farioli, A and Boffetta, P and Curti, S and Garzaro, G and La Vecchia, C and Mattioli, S and Spatari, G and Violante, FS}, title = {Response to: 'Are children more vulnerable to mesothelioma than adults? A comparison of mesothelioma risk among children and adults exposed non-occupationally to blue asbestos at Wittenoom' by Reid et al.}, journal = {Occupational and environmental medicine}, volume = {76}, number = {5}, pages = {355}, doi = {10.1136/oemed-2018-105637}, pmid = {30804167}, issn = {1470-7926}, mesh = {Adult ; Asbestos, Crocidolite ; Child ; Humans ; *Lung Neoplasms ; *Mesothelioma ; }, } @article {pmid30804166, year = {2019}, author = {Dalsgaard, SB and Würtz, ET and Hansen, J and Røe, OD and Omland, Ø}, title = {Environmental asbestos exposure in childhood and risk of mesothelioma later in life: a long-term follow-up register-based cohort study.}, journal = {Occupational and environmental medicine}, volume = {76}, number = {6}, pages = {407-413}, doi = {10.1136/oemed-2018-105392}, pmid = {30804166}, issn = {1470-7926}, mesh = {Aged ; Asbestos/*adverse effects ; Cohort Studies ; Denmark/epidemiology ; Environmental Exposure/adverse effects/statistics & numerical data ; Female ; Follow-Up Studies ; Humans ; Male ; Mesothelioma/epidemiology/*etiology ; Metallurgy/statistics & numerical data ; Middle Aged ; Registries/statistics & numerical data ; Risk Assessment/*methods ; }, abstract = {OBJECTIVE: To examine the risk of malignant mesothelioma (MM) in former pupils who attended primary school near an asbestos cement plant.

METHODS: A cohort of 12 111 former pupils, born 1940-1970, was established from individual historical records from four primary schools located at a distance of 100-750 m in the prevailing wind direction from an asbestos cement plant operating from 1928 to 1984 in Aalborg, Denmark. The school cohort and a comparison cohort consisting of 108 987 gender and 5-year frequency-matched subjects were followed up (2015) for MM in the Danish Cancer Registry. Using Cox regression, HRs were estimated for the incidence of MM. Adjustments for occupational and familial asbestos exposure were made with a job exposure matrix. An SIR analysis including latency periods testing the cancer incidence rate was performed with the comparison cohort as the reference rate.

RESULTS: The median person-years of follow-up were 62.5 years in the school cohort and 62.2 years in the comparison cohort. There were 32 males and 6 females of the former pupils who developed MM during the follow-up: HRmale 7.01 (95% CI 4.24 to 11.57), HRfemale 7.43 (95% CI 2.50 to 22.13). Those who attended school 250 m north of the plant had the highest HR for MM, 10.65 (95% Cl 5.82 to 19.48). No significant trend between school distance and risk of MM was established (p=0.35).

CONCLUSION: Our results suggest that boys and girls who attended schools and lived in the neighbourhood of an asbestos cement plant later in life have a significantly increased risk of MM.}, } @article {pmid30804152, year = {2019}, author = {Kim, M and Kim, HS}, title = {Clinicopathological Characteristics of Well-differentiated Papillary Mesothelioma of The Peritoneum: A Single-institutional Experience of 12 Cases.}, journal = {In vivo (Athens, Greece)}, volume = {33}, number = {2}, pages = {633-642}, pmid = {30804152}, issn = {1791-7549}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Mesothelioma/epidemiology/*pathology ; Middle Aged ; Neoplasm Recurrence, Local/epidemiology/*pathology ; Patient Selection ; Peritoneal Neoplasms/epidemiology/*pathology ; Peritoneum/pathology ; Pleural Neoplasms/epidemiology/*pathology ; }, abstract = {BACKGROUND/AIM: Well-differentiated papillary mesothelioma (WDPM) is histologically characterized by papillary architecture with fibrovascular cores, lined by bland mesothelial cells. We recently experienced a case of WDPM associated with multiple peritoneal inclusion cysts, which prompted us to initiate a comprehensive review of previously diagnosed WDPM cases.

MATERIALS AND METHODS: The clinicopathological characteristics and immunophenotype of 12 cases of peritoneal WDPM were investigated using a review of electronic medical records, pathological examination, and immunostaining.

RESULTS: The patients' ages ranged from 23 to 75 years. No patient had endometriosis or a previous history of asbestos exposure. Ten tumors were detected incidentally during surgery for other causes. Most tumors appeared as a small, single nodule on the peritoneal surface, but in three cases, WDPM presented as multiple lesions. All but one patient had no symptoms. All the patients examined are still well without postoperative recurrence. Histologically, all cases demonstrated typical papillary architecture with fibrovascular cores. The mesothelial cells lining the papillae consisted mostly of single row of cells, although areas of proliferation to multiple layers were observed in a few cases. Their nuclei appeared bland, but two cases exhibited mild nuclear atypia and prominent nucleoli. Immunostaining revealed that the mesothelial cells were positive for D2-40, cytokeratin 5/6, cytokeratin 7, and Wilms' tumor 1.

CONCLUSION: We herein demonstrated the clinicopathological characteristics of peritoneal WDPMs. WDPM has distinct pathological features. Although all cases we examined were uneventful after surgery, further surveillance is recommended since the biological behavior of WDPM is still uncertain.}, } @article {pmid30776941, year = {2019}, author = {Wang, F and Chen, Y and Wang, Y and Yin, Y and Qu, G and Song, M and Wang, H}, title = {Ultra-long silver nanowires induced mitotic abnormalities and cytokinetic failure in A549 cells.}, journal = {Nanotoxicology}, volume = {13}, number = {4}, pages = {543-557}, doi = {10.1080/17435390.2019.1571645}, pmid = {30776941}, issn = {1743-5404}, mesh = {A549 Cells ; Cell Culture Techniques ; Cell Proliferation/*drug effects ; Cell Survival/drug effects ; Cytokinesis/*drug effects ; Epithelial Cells/*drug effects/pathology ; Humans ; Mitosis/*drug effects ; Nanowires/chemistry/*toxicity ; Particle Size ; Silver/chemistry/*toxicity ; Surface Properties ; }, abstract = {Asbestos fiber has been associated with mesothelioma and lung cancer. However, the carcinogenic risks of other fiber nanomaterials with morphological similarities to asbestos have not been fully studied. Ultra-long silver nanowires (AgNWs) are increasingly used fiber-shaped nanomaterials with a high aspect ratio, but very few studies have investigated their health risks. Here, proliferation abnormalities of lung epithelial cells induced by ultra-long AgNWs were investigated. Ultra-long AgNW treatment induced dose- and diameter-dependent increase in the ratio of multinucleated cells. Further, proteins involved in mitosis and cytokinesis, including Aurora A, p-Histone 3 (ser10), RhoA, p-MLC, and myosin IIb, were significantly upregulated after an ultra-long AgNW treatment, leading to mitotic abnormalities and cytokinetic failure. Meanwhile, exposure to ultra-long AgNWs induced cell cycle arrest. Interestingly, a series of experiments demonstrated that ROS generation and Ag[+] release were not responsible for the multinucleation induced by ultra-long AgNWs, but ultra-long AgNWs in the intercellular bridge might obstruct the contractile ring and inhibit abscission of the cytokinetic furrow by direct physical contact. Altogether, our findings indicate that ultra-long AgNWs can induce chromosomal instability, which has important consequences for the safety of ultra-long AgNWs to human health.}, } @article {pmid30774332, year = {2019}, author = {Cova, E and Pandolfi, L and Colombo, M and Frangipane, V and Inghilleri, S and Morosini, M and Mrakic-Sposta, S and Moretti, S and Monti, M and Pignochino, Y and Benvenuti, S and Prosperi, D and Stella, G and Morbini, P and Meloni, F}, title = {Pemetrexed-loaded nanoparticles targeted to malignant pleural mesothelioma cells: an in vitro study.}, journal = {International journal of nanomedicine}, volume = {14}, number = {}, pages = {773-785}, pmid = {30774332}, issn = {1178-2013}, mesh = {Apoptosis/drug effects ; Biopsy ; CD146 Antigen/metabolism ; Cell Cycle/drug effects ; Cell Line, Tumor ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Endocytosis/drug effects ; Gold/chemistry ; Humans ; Lung Neoplasms/*drug therapy/pathology ; Mesothelioma/*drug therapy/pathology ; Mesothelioma, Malignant ; Metal Nanoparticles/*chemistry ; Pemetrexed/pharmacology/*therapeutic use ; Pleural Neoplasms/*drug therapy/pathology ; Reactive Oxygen Species/metabolism ; }, abstract = {PURPOSE: Malignant pleural mesothelioma (MPM) is an aggressive tumor characterized by poor prognosis. Its incidence is steadily increasing due to widespread asbestos exposure. There is still no effective therapy for MPM. Pemetrexed (Pe) is one of the few chemotherapeutic agents approved for advanced-stage disease, although the objective response to the drug is limited. The use of gold nanoparticles (GNPs) as a drug delivery system promises several advantages, including specific targeting of malignant cells, with increased intracellular drug accumulation and reduced systemic toxicity, and, in the case of MPM, direct treatment administration into the pleural space. This study aims at exploring CD146 as a potential MPM cell-specific target for engineered Pe-loaded GNPs and to assess their effectiveness in inhibiting MPM cell line growth.

METHODS: MPM cell lines and primary cultures obtained by pleural effusions from MPM patients were assayed for CD146 expression by flow cytometry. Internalization by MPM cell lines of fluorescent dye-marked GNPs decorated with a monoclonal anti CD146 coated GNPs (GNP-HC) was proven by confocal microscopy. The effects of anti CD146 coated GNPs loaded with Pe (GNP-HCPe) on MPM cell lines were evaluated by cell cycle (flow cytometry), viability (MTT test), clonogenic capacity (soft agar assay), ROS production (electric paramagnetic resonance), motility (wound healing assay), and apoptosis (flow cytometry).

RESULTS: GNP-HC were selectively uptaken by MPM cells within 1 hour. MPM cell lines were blocked in the S cell cycle phase in the presence of GNP-HCPe. Both cell viability and motility were significantly affected by nanoparticle treatment compared to Pe. Apoptotic rate and ROS production were significantly higher in the presence of nanoparticles. Clonogenic capacity was completely inhibited following nanoparticle internalization.

CONCLUSION: GNP-HCPe treatment displays in vitro antineoplastic action and is more effective than Pe alone in inhibiting MPM cell line malignant phenotype. The innovative use of specifically targeted GNPs opens the perspective of local intrapleural administration to avoid normal cell toxicity and enhance chemotherapy efficacy.}, } @article {pmid30773744, year = {2019}, author = {Yoshida, GJ}, title = {Beyond Stanton and Pott hypothesis; carbon nanotubes-induced malignant mesothelioma as a disease of gene loss.}, journal = {Journal of occupational health}, volume = {61}, number = {2}, pages = {203-205}, pmid = {30773744}, issn = {1348-9585}, mesh = {Animals ; Asbestos/adverse effects ; Genes, p16 ; Humans ; Lung Neoplasms/*chemically induced/*genetics ; Mesothelioma/*chemically induced/*genetics ; Mesothelioma, Malignant ; Mice ; Nanotubes, Carbon/*adverse effects ; Occupational Exposure/adverse effects ; }, } @article {pmid30770142, year = {2019}, author = {Douglas, T and Van den Borre, L}, title = {Asbestos neglect: Why asbestos exposure deserves greater policy attention.}, journal = {Health policy (Amsterdam, Netherlands)}, volume = {123}, number = {5}, pages = {516-519}, doi = {10.1016/j.healthpol.2019.02.001}, pmid = {30770142}, issn = {1872-6054}, mesh = {*Asbestos ; *Carcinogens, Environmental ; Developing Countries ; Environmental Exposure/*adverse effects ; Health Policy ; Humans ; Lung Neoplasms/chemically induced/prevention & control ; Mesothelioma/chemically induced/prevention & control ; Occupational Exposure/adverse effects ; }, abstract = {While many public health threats are now widely appreciated by the public, the risks from asbestos exposure remain poorly understood, even in high-risk groups. This article makes the case that asbestos exposure is an important, ongoing global health threat, and argues for greater policy efforts to raise awareness of this threat. It also proposes the extension of asbestos bans to developing countries and increased public subsidies for asbestos testing and abatement.}, } @article {pmid30759891, year = {2019}, author = {Bertrand, P and Blanquart, C and Héroguez, V}, title = {The ROMP: A Powerful Approach to Synthesize Novel pH-Sensitive Nanoparticles for Tumor Therapy.}, journal = {Biomolecules}, volume = {9}, number = {2}, pages = {}, pmid = {30759891}, issn = {2218-273X}, mesh = {Animals ; Antineoplastic Agents/chemistry/*pharmacology ; Cell Proliferation/drug effects ; Drug Carriers/chemistry ; Drug Delivery Systems ; Histone Deacetylase Inhibitors/chemistry/*pharmacology ; Humans ; Hydrogen-Ion Concentration ; Nanoparticles/*chemistry ; Neoplasms/*drug therapy/pathology ; Polymerization ; }, abstract = {Fast clearance, metabolism, and systemic toxicity are major limits for the clinical use of anti-cancer drugs. Histone deacetylase inhibitors (HDACi) present these defects, despite displaying promising anti-tumor properties on tumor cells in vitro and in in vivo models of cancer. The specific delivery of anti-cancer drugs into the tumor should improve their clinical benefit by limiting systemic toxicity and by increasing the anti-tumor effect. This paper deals with the synthesis of the polymeric nanoparticle platform, which was produced by Ring-Opening Metathesis Polymerization (ROMP), able to release anti-cancer drugs in dispersion, such as histone deacetylase inhibitors, into mesothelioma tumors. The core-shell nanoparticles (NPs) have stealth properties due to their poly(ethylene oxide) shell and can be viewed as universal nano-carriers on which any alkyne-modified anti-cancer molecule can be grafted by click chemistry. A cleavage reaction of the chemical bond between NPs and drugs through the contact of NPs with a medium presenting an acidic pH, which is typically a cancer tumor environment or an acidic intracellular compartment, induces a controlled release of the bioactive molecule in its native form. In our in vivo syngeneic model of mesothelioma, a highly selective accumulation of the particles in the tumor was obtained. The release of the drugs led to an 80% reduction of tumor weight for the best compound without toxicity. Our work demonstrates that the use of theranostic nanovectors leads to an optimized delivery of epigenetic inhibitors in tumors, which improves their anti-tumor properties in vivo.}, } @article {pmid30754975, year = {2018}, author = {Pelclová, D}, title = {Diagnostics and acknowledgement of occupational diseases - topics and challenges in the Czech Republic.}, journal = {Casopis lekaru ceskych}, volume = {157}, number = {8}, pages = {396-399}, pmid = {30754975}, issn = {0008-7335}, mesh = {*Asbestos/adverse effects ; *Asthma/diagnosis/etiology ; Czech Republic ; Humans ; *Mesothelioma/diagnosis/etiology ; *Occupational Diseases/diagnosis/therapy ; }, abstract = {The causes of occupational diseases are changing, thats why a regular update of Czech List of Occupational Diseases is needed. New compensable occupational diseases, such as cancer of the larynx and ovarian cancer due to asbestos, and chronic obstructive pulmonary diseases due to black coal dust were included in the last two updates of the Czech List. The need of an early examination at the Centers of Occupational Diseases is stressed in this article, especially before a surgery or other treatment of epicondylitis and carpal tunnel syndrome. These treatments may suppress the diagnostic hallmarks requested for acknowledgements of these disorders. Extrinsic allergic alveolitis, allergic rhinitis and bronchial asthma are underdiagnosed, and isocyanates belong among the key factors. Only about 10 % patients with mesotheliomas due to asbestos are compensated. The latency in cancers due to asbestos may reach more than 50 years.}, } @article {pmid30744695, year = {2019}, author = {Weber, DG and Brik, A and Casjens, S and Burek, K and Lehnert, M and Pesch, B and Taeger, D and Brüning, T and Johnen, G and , }, title = {Are circulating microRNAs suitable for the early detection of malignant mesothelioma? Results from a nested case-control study.}, journal = {BMC research notes}, volume = {12}, number = {1}, pages = {77}, pmid = {30744695}, issn = {1756-0500}, mesh = {Adult ; Asbestosis/blood ; Biomarkers, Tumor/*blood ; Case-Control Studies ; Circulating MicroRNA/*blood ; Early Detection of Cancer/*standards ; Humans ; Lung Neoplasms/blood/*diagnosis ; Male ; Mesothelioma/blood/*diagnosis ; Mesothelioma, Malignant ; MicroRNAs/*blood ; Middle Aged ; Prodromal Symptoms ; Sensitivity and Specificity ; }, abstract = {OBJECTIVE: Malignant mesothelioma is an aggressive cancer of the serous membranes. For the detection of the tumor at early stages non- or minimally-invasive biomarkers are needed. The circulating biomarkers miR-132-3p, miR-126-3p, and miR-103a-3p were analyzed in a nested case-control study using plasma samples from 17 prediagnostic mesothelioma cases and 34 matched asbestos-exposed controls without a malignant disease.

RESULTS: Using prediagnostic plasma samples collected in median 8.9 months prior the clinical diagnosis miR-132-3p, miR-126-3p, and miR-103a-3p revealed 0% sensitivity on a defined specificity of 98%. Thus, the analyzed miRNAs failed to detect the cancer in prediagnostic samples, showing that they are not feasible for the early detection of malignant mesothelioma. However, the miRNAs might still serve as possible markers for prognosis and response to therapy, but this needs to be analyzed in appropriate studies.}, } @article {pmid30741658, year = {2019}, author = {García-Ibáñez, J and Cayuelas-Rubio, C and Durán-Rivera, A and Mitjana-Biosca, S and Monzó-Cataluña, A and Sánchez Ballester, F and Ramos de Campos, M and Ramos de Campos, M and López-Alcina, E}, title = {[Report of two cases of malignant mesothelioma of the tunica vaginalis.].}, journal = {Archivos espanoles de urologia}, volume = {72}, number = {1}, pages = {85-88}, pmid = {30741658}, issn = {0004-0614}, mesh = {Aged ; Humans ; *Lung Neoplasms ; Male ; *Mesothelioma/diagnosis ; *Testicular Hydrocele ; *Testicular Neoplasms/diagnosis ; }, abstract = {OBJECTIVE: Paratesticular mesothelioma isan infrequent tumor and only 250 cases have been published.It originates in the scrotal tunica vaginalis. It represents0.3-1.4% of mesotheliomas and it predominates inpatients with history of asbestos exposure and old age. Itsdiagnosis is usually casual. Our objective is to present thecases that occurred in our service with malignant paratesticularmesothelioma and to carry out a review of the currentliterature on this pathology.

METHODS: We report two cases diagnosed with malignantparatesticular mesothelioma that happened in the lasttwo years.

RESULT: The first case was a 73-year-old male with asymptomatichydrocele. The second was a 57-year-oldmale who had testicular pain and hydrocele. Both werediagnosed of mesothelioma after hydrocelectomy. The firsttreatment was radical orchiectomy in both cases. The firstpatient did not need more treatments. The second patientpresented pulmonary nodules, lymphadenopathy and localrelapse, which was treated with chemotherapy and localresection.

CONCLUSION: Paratesticular mesothelioma is an infrequenttumor. Scrotal mass associated with hydrocele is thetypical form of presentation. Surgical treatment consists ofradical orchiectomy. They have poor prognosis because inmost cases there is rapid local and dissemination.}, } @article {pmid30719319, year = {2019}, author = {Guo, X and Watanabe, J and Takahashi, K and Hayashi, T and Kurose, N and Sasaguri, Y and Uramoto, H and Iwagaki, H and Nabeshima, K and Yamada, S}, title = {Localized malignant pleural mesothelioma arising in the interlobar fissure: a unique surgical case masquerading clinicopathologically as primary lung adenocarcinoma.}, journal = {SAGE open medical case reports}, volume = {7}, number = {}, pages = {2050313X18824802}, pmid = {30719319}, issn = {2050-313X}, abstract = {An 80-year-old male with previous workplace exposure to asbestos presented with a history of an increase in the pulmonary-to-hilar mass, measuring more than 50 mm in diameter, likely in the right lower lobe. We first interpreted it as suspicious of primary lung adenocarcinoma with direct invasion to the right hilar lymph node. A right middle and lower lobectomy with partial resection of upper lobe was performed, and gross examination showed a hilar tumor lesion, involving the middle/lower lobe to hilar lymph node and looking whitish to yellow-grayish, partly adjacent to the right pulmonary artery. On microscopic examination, the tumor was located on the extrapulmonary, interlobar pleural fissure, predominantly composed of a proliferation of atypical epithelioid cells, often arranged in an irregular and fused tubular growth pattern with an involvement of pulmonary artery. Immunohistochemically, these atypical cells are positive for several mesothelial markers, including calretinin, cytokeratin 5/6, and WT-1, whereas negative for thyroid transcription factor 1. Furthermore, p16 deletions were specifically detected by fluorescence in situ hybridization, and electron microscopy showed numerous, significantly elongated microvilli. Taken together, we finally made a diagnosis of localized malignant pleural mesothelioma, epithelioid-type, arising in the right interlobar fissure between lower and middle lobes. We should be aware that, owing to its characteristic features, clinicians and pathologists might be able to raise interlobar fissure localized malignant pleural mesothelioma as one of the differential diagnoses, based on careful clinicopathological examinations.}, } @article {pmid30711965, year = {2019}, author = {Salo, SAS and Ilonen, I and Laaksonen, S and Myllärniemi, M and Salo, JA and Rantanen, T}, title = {Malignant Peritoneal Mesothelioma: Treatment Options and Survival.}, journal = {Anticancer research}, volume = {39}, number = {2}, pages = {839-845}, doi = {10.21873/anticanres.13183}, pmid = {30711965}, issn = {1791-7530}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Asbestos/adverse effects ; Cytoreduction Surgical Procedures/mortality ; Female ; Finland ; Humans ; Hyperthermia, Induced ; Lung Neoplasms/*drug therapy/mortality/*surgery ; Male ; Mesothelioma/*drug therapy/mortality/*surgery ; Mesothelioma, Malignant ; Middle Aged ; Peritoneal Neoplasms/*drug therapy/mortality/*surgery ; Prognosis ; Retrospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND: Malignant peritoneal mesothelioma (MPeM) is a rare type of cancer with a poor prognosis. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) have been shown to improve survival. Treatment and survival of patients with MPeM have not been previously studied in Finland.

MATERIALS AND METHODS: The data consisted of all patients diagnosed with MPeM during years 2000-2012 in Finland, including cancer notifications, death certificates and information about asbestos exposure.

RESULTS: Among 50/94 (53.2%) patients treated for MPeM, 44/50 (88.0%) were treated palliatively, 4/50 (8.0%) with radical surgery and chemotherapy, and 2/50 (4.0%) with CRS plus HIPEC. Five-year survival was 50.0% for those treated with CRS plus HIPEC and 75.0% for those treated with radical surgery and chemotherapy. Radical surgery with chemotherapy was associated with significantly longer survival compared to radiation (p=0.008), chemotherapy and radiation (p=0.043), surgery, chemotherapy and radiation (p=0.039), and palliative surgery (p=0.009).

CONCLUSION: Treatment of MPeM is heterogenic in Finland. CRS plus HIPEC, and radical surgery with chemotherapy seem to increase the survival. Patients considered candidates for radical surgery should be sent to specialized centers for further assessment.}, } @article {pmid30706690, year = {2019}, author = {Rojas, L and Cardona, AF and Trejo-Rosales, R and Zatarain-Barrón, ZL and Ramírez-Tirado, LA and Ruiz-Patiño, A and Campos Gómez, S and Corrales, L and Oblitas, G and Bacon, L and Martín, C and de Lima, VCC and Freitas, HC and Mas, L and Vargas, C and Carranza, H and Otero, J and Pérez, MA and González, L and Chirinos, L and Granados, ST and Rodriguez, J and Báez, R and Remolina Bonilla, YA and Núñez Cerrillo, G and Archila, P and Cuello, M and Karachaliou, N and Rosell, R and Arrieta, O and , }, title = {Characteristics and long-term outcomes of advanced pleural mesothelioma in Latin America (MeSO-CLICaP).}, journal = {Thoracic cancer}, volume = {10}, number = {3}, pages = {508-518}, pmid = {30706690}, issn = {1759-7714}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Cisplatin/therapeutic use ; Female ; Humans ; Latin America/epidemiology ; Lung Neoplasms/drug therapy/*epidemiology/pathology/surgery ; Male ; Mesothelioma/drug therapy/*epidemiology/pathology/surgery ; Mesothelioma, Malignant ; Middle Aged ; Pemetrexed/therapeutic use ; Platinum/*therapeutic use ; Pleural Neoplasms/drug therapy/*epidemiology/pathology/surgery ; Progression-Free Survival ; Thoracic Surgical Procedures/methods ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive tumor, associated with poor prognosis. There is a lack of information about the clinical and pathological features related with survival in the Latin American population.

METHODS: The MeSO-CLICaP registry identified 302 patients with advanced MPM diagnosed and treated between January 2008 and March 2016. The Cox model was applied to determine the variables associated with survival. A random forest tree model was built to predict the response to first-line chemotherapy among Latin American patients.

RESULTS: The median age was 61.1 years (SD 10.6 years), 191 (63.2%) were men, 65.9% were ever smokers, and 38.7% had previous exposure to asbestos. A total of 237 (78.5%) had epithelioid tumors, and 188 (62.3%) and 114 (37.7%) cases had stage III or IV MPM, respectively. A total of 49 patients (16.2%) underwent pleurectomy, 57 (18.9%) received radiotherapy, and 279 patients received first-line platinum-based chemotherapy. The overall response rate to first-line chemotherapy was 40.4%, progression-free survival to first-line treatment was 5.7 months (95% CI 4.9-6.5), and 63 (20.8%) patients had pemetrexed maintenance. The median overall survival was 16.8 months (95% CI 13.0-20.5), and multivariate analysis found that stage (P = 0.013), and pleurodesis (P = 0.048), were independent prognostic factors for first-line overall survival. The model to predict response to first-line chemotherapy obtained a 0.98 area under the curve, a sensitivity of 93%, and a specificity of 95% for detecting responders and non-responders.

CONCLUSION: This study identifies factors associated with clinical benefit from chemotherapy among advanced MPM Latin American patients, emphasizing the impact of histology and the clinical benefit of chemotherapy on outcomes.}, } @article {pmid30706505, year = {2019}, author = {Sun, H}, title = {North-south gradient of mesothelioma and asbestos consumption-production in the United States-Progresses since the 1st asbestos partial ban in 1973.}, journal = {American journal of industrial medicine}, volume = {62}, number = {4}, pages = {337-346}, doi = {10.1002/ajim.22955}, pmid = {30706505}, issn = {1097-0274}, mesh = {*Asbestos ; Asbestos, Amphibole ; Asbestos, Serpentine ; Female ; Geography ; Humans ; Incidence ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology ; Mesothelioma, Malignant ; Mining/*statistics & numerical data ; United States/epidemiology ; }, abstract = {BACKGROUND: Temporal trends and broad geographical distributions of asbestos use and the incidence of malignant mesothelioma (MM) in the US still need to be studied.

METHODS: Data on asbestos consumption and production between 1900 and 2015 and MM mortality and incidence rates between 1975 and 2015 in the US were examined. Spatial distributions of MM mortality and incidence rates and their association with climate zone were analyzed.

RESULTS: Decline of MM incidence and mortality rates in the US occurred about 20 years after the peak of asbestos consumption-production in 1973. There are apparent north-south (N-S) gradients in MM mortality and incidence rates in the US.

CONCLUSION: Recent decline of MM incidence and mortality rates in the US may be associated with reduced US asbestos consumption. N-S MM gradients between 1999 and 2015 were likely related to larger asbestos requirements in building materials in the northern states.}, } @article {pmid30702033, year = {2020}, author = {Germine, M and Puffer, JH}, title = {Analytical transmission electron microscopy of amosite asbestos from South Africa.}, journal = {Archives of environmental & occupational health}, volume = {75}, number = {1}, pages = {36-44}, doi = {10.1080/19338244.2018.1556201}, pmid = {30702033}, issn = {2154-4700}, mesh = {Asbestos, Amosite/*chemistry ; Microscopy, Electron, Scanning ; Microscopy, Electron, Transmission ; Molecular Structure ; South Africa ; }, abstract = {Using the recognized amosite standard, we have performed transmission electron microscopy (TEM), scanning electron microscopy (SEM), and chemical analyses. We use high-resolution transmission electron microscopy (HRTEM) and zone-axis selected area electron diffraction (SAED) to describe the molecular structure of the fibers. We find that both microscopic observational evidence and statistical dimensional characteristics indicate that the amosite fibers are formed by longitudinal splitting, with surfaces produced by fine twinning and lateral boundaries formed by parting parallel to the planes of double and triple sheets of amphibole chain structures. Our findings indicate that amosite would not be regulated under current asbestos regulations, which define amphibole asbestos as whole crystals that are not split and that form fibril bundles, not found in our standard. However, it is fully documented that amosite causes mesothelioma, lung cancer, and asbestosis.}, } @article {pmid30687679, year = {2018}, author = {Visonà, SD and Villani, S and Manzoni, F and Chen, Y and Ardissino, G and Russo, F and Moretti, M and Javan, GT and Osculati, A}, title = {Impact of asbestos on public health: a retrospective study on a series of subjects with occupational and non-occupational exposure to asbestos during the activity of Fibronit plant (Broni, Italy).}, journal = {Journal of public health research}, volume = {7}, number = {3}, pages = {1519}, pmid = {30687679}, issn = {2279-9028}, abstract = {The goal of this study is to understand more about the role of asbestos in causing human diseases, first of all mesothelioma, by investigating a large series of deaths due to asbestos-related diseases (ARDs). The main aim is to clarify if even very low amounts of asbestos can cause mesothelioma and other ARDs, as well as to find out if a different individual vulnerability can be important. This retrospective study included 188 subjects who died from asbestos related diseases in 2000-2017 in the area around Broni, Italy, where an important asbestos cement factory had been active from 1932 until 1993. In each case, a forensic autopsy has been performed. In order to perform the present study, the records were retrieved, including the clinical files, the autopsy, and the histological report. The statistical analysis performed showed that there was a significant relation between the cause of death (mesothelioma, lung cancer or asbestosis) and the kind of exposure (occupational, neighborhood or household), showing that all the subjects not exposed occupationally (and, therefore, exposed to lower amounts of asbestos) died from mesothelioma, whereas the individuals who used to work at the plant died also from other caused (asbestosis, lung cancer). Significant differences were highlighted examining the distribution of the causes of death according to the smoking habits. Moreover, among the mesothelioma patients, the survival time was shorter in the subjects with a neighborhood or household exposure than in the occupationally exposed individuals. The study provided meaningful data about the role of asbestos in causing human pathologies. In particular, the present data appear to support the hypothesis that even an exposure to a very little amount of asbestos can cause mesothelioma in hypersusceptible subjects (probably, on a genetic basis).}, } @article {pmid30687504, year = {2019}, author = {Matthews, C and Freeman, C and Sharples, LD and Fox-Rushby, J and Tod, A and Maskell, NA and Edwards, JG and Coonar, AS and Sivasothy, P and Hughes, V and Rahman, NM and Waller, DA and Rintoul, RC}, title = {MesoTRAP: a feasibility study that includes a pilot clinical trial comparing video-assisted thoracoscopic partial pleurectomy decortication with indwelling pleural catheter in patients with trapped lung due to malignant pleural mesothelioma designed to address recruitment and randomisation uncertainties and sample size requirements for a phase III trial.}, journal = {BMJ open respiratory research}, volume = {6}, number = {1}, pages = {e000368}, pmid = {30687504}, issn = {2052-4439}, support = {G0600475/MRC_/Medical Research Council/United Kingdom ; PB-PG-1014-35050/DH_/Department of Health/United Kingdom ; }, mesh = {Adult ; Catheters, Indwelling ; Clinical Trials, Phase III as Topic ; England/epidemiology ; Feasibility Studies ; Female ; Humans ; Lung Neoplasms/complications/mortality/*surgery ; Male ; Mesothelioma/complications/mortality/*surgery ; Mesothelioma, Malignant ; Multicenter Studies as Topic ; Observational Studies as Topic ; Pilot Projects ; Pleural Effusion, Malignant/etiology/mortality/*surgery ; Pleural Neoplasms/complications/mortality/*surgery ; Pleurodesis/adverse effects/instrumentation/*methods ; Randomized Controlled Trials as Topic ; Sample Size ; Survival Analysis ; Thoracic Surgery, Video-Assisted/adverse effects/instrumentation/*methods ; Treatment Outcome ; }, abstract = {INTRODUCTION: One of the most debilitating symptoms of malignant pleural mesothelioma (MPM) is dyspnoea caused by pleural effusion. MPM can be complicated by the presence of tumour on the visceral pleura preventing the lung from re-expanding, known as trapped lung (TL). There is currently no consensus on the best way to manage TL. One approach is insertion of an indwelling pleural catheter (IPC) under local anaesthesia. Another is video-assisted thoracoscopic partial pleurectomy/decortication (VAT-PD). Performed under general anaesthesia, VAT-PD permits surgical removal of the rind of tumour from the visceral pleura thereby allowing the lung to fully re-expand.

METHODS AND ANALYSIS: MesoTRAP is a feasibility study that includes a pilot multicentre, randomised controlled clinical trial comparing VAT-PD with IPC in patients with TL and pleural effusion due to MPM. The primary objective is to measure the SD of visual analogue scale scores for dyspnoea following randomisation and examine the patterns of change over time in each treatment group. Secondary objectives include documenting survival and adverse events, estimating the incidence and prevalence of TL in patients with MPM, examining completion of alternative forms of data capture for economic evaluation and determining the ability to randomise 38 patients in 18 months.

ETHICS AND DISSEMINATION: This study was approved by the East of England-Cambridge Central Research Ethics Committee and the Health Research Authority (reference number 16/EE/0370). We aim to publish the outputs of this work in international peer-reviewed journals compliant with an Open Access policy.

TRIAL REGISTRATION: NCT03412357.}, } @article {pmid30686559, year = {2019}, author = {Neviere, Z and Berthet, P and Polycarpe, F and Dubos-Arvis, C and Dô, P and Gervais, R}, title = {[Malignant mesothelioma and constitutional BAP1 gene mutations].}, journal = {Revue des maladies respiratoires}, volume = {36}, number = {2}, pages = {241-248}, doi = {10.1016/j.rmr.2017.11.014}, pmid = {30686559}, issn = {1776-2588}, mesh = {Aftercare/methods ; Genetic Counseling ; Genetic Predisposition to Disease ; Genetic Testing ; Humans ; Lung Neoplasms/diagnosis/epidemiology/*genetics/*therapy ; Medical Oncology/methods ; Mesothelioma/diagnosis/epidemiology/*genetics/*therapy ; Mesothelioma, Malignant ; *Mutation ; Referral and Consultation ; Tumor Suppressor Proteins/*genetics/physiology ; Ubiquitin Thiolesterase/*genetics/physiology ; }, abstract = {Malignant mesothelioma is a rare tumour, usually the result of asbestos exposure. Several cases of familial aggregation have been reported and recently shown to be associated with constitutional mutations of the BAP1 gene. BAP1 is a deubiquitinating enzyme implicated in several different cellular mechanisms such as the repair or differentiation of DNA. About a half of malignant mesotheliomas present a somatic, bi-allelic inactivation of BAP1, demonstrated by nuclear extinction on histochemistry. Constitutional alterations of BAP1 are extremely rare. Present in the heterozygous state they are transmitted as an autosomal dominant. They are associated with a risk of developing other tumours such as uveal and cutaneous melanomas, benign melanocytic tumours (melanocytic BAP1-mutated atypical intradermal tumour or MBAITS) and clear cell renal carcinomas. The causal link between mesothelioma and germinal mutations of BAP1 has still not been clearly identified. At present there is, in France, no consensus on recommendations for the management of patients with these mutations. This article is a synthesis of the literature on the functions of the BAP1 gene, the tumour risks related to its alteration and the follow up of patients bearing a constitutional mutation.}, } @article {pmid30685089, year = {2019}, author = {Abayasiriwardana, KS and Wood, MK and Prêle, CM and Birnie, KA and Robinson, BW and Laurent, GJ and McAnulty, RJ and Mutsaers, SE}, title = {Inhibition of collagen production delays malignant mesothelioma tumor growth in a murine model.}, journal = {Biochemical and biophysical research communications}, volume = {510}, number = {2}, pages = {198-204}, doi = {10.1016/j.bbrc.2019.01.057}, pmid = {30685089}, issn = {1090-2104}, support = {/MRC_/Medical Research Council/United Kingdom ; /CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Animals ; Antineoplastic Agents/pharmacology ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Collagen/antagonists & inhibitors/*biosynthesis ; Disease Models, Animal ; Extracellular Matrix/metabolism ; Female ; Humans ; Inflammation ; Lung Neoplasms/*metabolism/pathology ; Mesothelioma/*metabolism/pathology ; Mesothelioma, Malignant ; Mice ; Mice, Inbred CBA ; Pleural Neoplasms/*metabolism/pathology ; Thiazolidines/pharmacology ; Transforming Growth Factor beta/metabolism ; }, abstract = {Malignant mesothelioma is an aggressive fibrous tumor, predominantly of the pleura, with a very poor prognosis. Cell-matrix interactions are recognized important determinants of tumor growth and invasiveness but the role of the extracellular matrix in mesothelioma is unknown. Mesothelioma cells synthesize collagen as well as transforming growth factor-beta (TGF-β), a key regulator of collagen production. This study examined the effect of inhibiting collagen production on mesothelioma cell proliferation in vitro and tumor growth in vivo. Collagen production by mesothelioma cells was inhibited by incubating cells in vitro with the proline analogue thiaproline (thiazolidine-4-carboxylic acid) or by oral administration of thiaproline in a murine tumor model. Cell cytotoxicity was measured using neutral red uptake and lactate dehydrogenase assays. Proliferation was measured by tritiated thymidine incorporation, and inflammatory cell influx, proliferation, apoptosis and angiogenesis in tumors examined by immunohistochemical labelling. Tumor size was determined by tumor weight and collagen production was measured by HPLC. Thiaproline at non-toxic doses significantly reduced basal and TGF-β-induced collagen production by over 50% and cell proliferation by over 65%. In vivo thiaproline administration inhibited tumor growth at 10 days, decreasing the median tumor weight by 80%. The mean concentration of collagen was 50% lower in the thiaproline-treated tumors compared with the controls. There were no significant differences in vasculature or inflammatory cell infiltration but apoptosis was increased in thiaproline treated tumors at day 10. In conclusion, these observations strongly support a role for collagen in mesothelioma growth and establish the potential for inhibitors of collagen synthesis in mesothelioma treatment.}, } @article {pmid30684047, year = {2019}, author = {Warby, A and Dhillon, HM and Kao, S and Vardy, JL}, title = {Managing malignant pleural mesothelioma: experience and perceptions of health care professionals caring for people with mesothelioma.}, journal = {Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer}, volume = {27}, number = {9}, pages = {3509-3519}, pmid = {30684047}, issn = {1433-7339}, support = {n/a//New South Wales Workers' Compensation Dust Disease Board/ ; }, mesh = {Adult ; Aged ; *Attitude of Health Personnel ; Caregivers/*psychology ; Communication ; Female ; Humans ; Lung Neoplasms/pathology/*therapy ; Male ; Medical Oncology ; Mesothelioma/pathology/*therapy ; Mesothelioma, Malignant ; Middle Aged ; Palliative Care/methods ; Pleural Neoplasms/pathology/*therapy ; Practice Patterns, Physicians'/*statistics & numerical data ; Referral and Consultation ; Refusal to Treat/*statistics & numerical data ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) has a poor prognosis and heavy symptom burden. Here, we investigate health professionals' attitudes to management and decision-making in people with MPM.

METHODS: Survey questions were based on previous interviews with health professionals, MPM patients, and caregivers. Surveys were sent to specialist doctors and nurses who treat MPM.

RESULTS: Surveys were completed by 107 doctors and 19 nurses from January-September 2014. Most doctors were respiratory physicians (50%) or medical oncologists (35%). Overall, 90% of doctors estimated > 10% of eligible MPM patients did not receive chemotherapy; 43% estimated the rate was > 20%. Doctors believed clinical barriers to chemotherapy were clinician nihilism (70%); non-referral to medical oncology (49%); and lack of specialists in rural/regional areas (44%). Nurses perceived barriers as follows: delayed diagnosis (74%); non-referral to medical oncology (63%); lack of clinician knowledge (58%). Patient-related barriers were negative perception of chemotherapy (83%) and belief survival benefit not worthwhile (63%). Doctors' preference in decision-making was for the patient to make the decision while strongly considering the doctor's opinion (33%); equally with the doctor (29%); and using knowledge gained (23%). Nurses described their roles as providing patient support (100%); information (95%); intermediary (74%); and link to palliative care (74%). Overall, 95% believed they enabled better resource allocation and provided patients with holistic care (95%); clearer communication (89%); more time (89%); additional information (89%); timely referrals (89%).

CONCLUSIONS: Caring for patients with MPM is challenging and complex. Health care professionals believe under-utilisation of chemotherapy is occurring, primarily due to clinician nihilism and lack of medical oncology referral.}, } @article {pmid30663400, year = {2018}, author = {Wang, QQ and Zheng, GQ and Yang, DL and Liang, YF and Yin, WJ and Su, SS}, title = {Pretreatment Controlling Nutritional Status Score and Lactate Dehydrogenase as Predictive Markers of Survival in Patients with Malignant Peritoneal Mesothelioma.}, journal = {Nutrition and cancer}, volume = {70}, number = {8}, pages = {1264-1274}, doi = {10.1080/01635581.2018.1560481}, pmid = {30663400}, issn = {1532-7914}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage/therapeutic use ; Asbestos/toxicity ; Biomarkers, Tumor/blood ; Female ; Humans ; L-Lactate Dehydrogenase/*blood ; Male ; Mesothelioma/drug therapy/*mortality/surgery ; Middle Aged ; Nutritional Status/*physiology ; Peritoneal Neoplasms/drug therapy/*mortality/surgery ; Prognosis ; ROC Curve ; }, abstract = {OBJECTIVE: To investigate the relationships between the Controlling Nutritional Status (CONUT) score and ascites fluid lactate dehydrogenase (LDH) level, and prognosis in patients with malignant peritoneal mesothelioma (MPeM).

METHODS: A total of 125 patients with MPeM were selected for the study using a pathological screening method. Once the diagnosis is established, before the treatment their clinical characteristics and nutritional evaluations were recorded including CONUT score and ascites LDH level. The associations between CONUT, ascites LDH, and other clinicopathological features including body mass index, asbestos exposure, pathological type, and treatment method were analyzed. Prognostic parameters predicting overall survival (OS) were analyzed by Cox regression.

RESULTS: High CONUT score, high ascites LDH level were positively associated with poor prognosis in patients with MPeM according to univariate analyses (P < 0.001, P < 0.001, respectively), and CONUT score and ascites LDH were independent predictors of a poor prognosis according to multivariate analysis. When the CONUT score is greater than 3 and the ascites LHD is greater than 474 IU/l, it indicates a poor prognosis.

CONCLUSIONS: CONUT score and ascites LDH are important factors influencing the prognosis of MPeM patients and should thus be considered in clinical applications.}, } @article {pmid30659154, year = {2019}, author = {Villanova, T and Gesmundo, I and Audrito, V and Vitale, N and Silvagno, F and Musuraca, C and Righi, L and Libener, R and Riganti, C and Bironzo, P and Deaglio, S and Papotti, M and Cai, R and Sha, W and Ghigo, E and Schally, AV and Granata, R}, title = {Antagonists of growth hormone-releasing hormone (GHRH) inhibit the growth of human malignant pleural mesothelioma.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {6}, pages = {2226-2231}, pmid = {30659154}, issn = {1091-6490}, mesh = {Animals ; Antineoplastic Agents/*pharmacology ; Apoptosis/drug effects ; Cell Line, Tumor ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Disease Models, Animal ; Gene Expression ; Growth Hormone-Releasing Hormone/*antagonists & inhibitors/genetics/metabolism ; Humans ; Lung Neoplasms/drug therapy/*metabolism/*pathology ; Mesothelioma/drug therapy/*metabolism/*pathology ; Mesothelioma, Malignant ; Mice ; Mitochondria/drug effects/metabolism ; Pleural Neoplasms/drug therapy/*metabolism/*pathology ; Receptors, Neuropeptide/genetics/metabolism ; Receptors, Pituitary Hormone-Regulating Hormone/genetics/metabolism ; Xenograft Model Antitumor Assays ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive malignancy associated with exposure to asbestos, with poor prognosis and no effective therapies. The strong inhibitory activities of growth hormone-releasing hormone (GHRH) antagonists have been demonstrated in different experimental human cancers, including lung cancer; however, their role in MPM remains unknown. We assessed the effects of the GHRH antagonists MIA-602 and MIA-690 in vitro in MPM cell lines and in primary MPM cells, and in vivo in MPM xenografts. GHRH, GHRH receptor, and its main splice variant SV1 were found in all the MPM cell types examined. In vitro, MIA-602 and MIA-690 reduced survival and proliferation in both MPM cell lines and primary cells and showed synergistic inhibitory activity with the chemotherapy drug pemetrexed. In MPM cells, GHRH antagonists also regulated activity and expression of apoptotic molecules, inhibited cell migration, and reduced the expression of matrix metalloproteinases. These effects were accompanied by impairment of mitochondrial activity and increased production of reactive oxygen species. In vivo, s.c. administration of MIA-602 and MIA-690 at the dose of 5 μg/d for 4 wk strongly inhibited the growth of MPM xenografts in mice, along with reduction of tumor insulin-like growth factor-I and vascular endothelial growth factor. Overall, these results suggest that treatment with GHRH antagonists, alone or in association with chemotherapy, may offer an approach for the treatment of MPM.}, } @article {pmid30651596, year = {2019}, author = {Sépult, C and Bellefroid, M and Rocks, N and Donati, K and Gérard, C and Gilles, C and Ludwig, A and Duysinx, B and Noël, A and Cataldo, D}, title = {ADAM10 mediates malignant pleural mesothelioma invasiveness.}, journal = {Oncogene}, volume = {38}, number = {18}, pages = {3521-3534}, pmid = {30651596}, issn = {1476-5594}, mesh = {ADAM10 Protein/*genetics ; Amyloid Precursor Protein Secretases/*genetics ; Animals ; Cadherins/genetics ; Cell Line, Tumor ; Cell Movement/*genetics ; Disease Progression ; Down-Regulation/genetics ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Lung Neoplasms/*genetics/*pathology ; Male ; Membrane Proteins/*genetics ; Mesothelioma/*genetics/*pathology ; Mesothelioma, Malignant ; Mice ; Mice, Inbred BALB C ; Pleural Neoplasms/*genetics/*pathology ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive cancer with limited therapeutic options and treatment efficiency. Even if the latency period between asbestos exposure, the main risk factor, and mesothelioma development is very long, the local invasion of mesothelioma is very rapid leading to a mean survival of one year after diagnosis. ADAM10 (A Disintegrin And Metalloprotease) sheddase targets membrane-bound substrates and its overexpression is associated with progression in several cancers. However, nothing is known about ADAM10 implication in MPM. In this study, we demonstrated higher ADAM10 expression levels in human MPM as compared to control pleural samples and in human MPM cell line. This ADAM10 overexpression was also observed in murine MPM samples. Two mouse mesothelioma cell lines were used in this study including one primary cell line obtained by repeated asbestos fibre injections. We show, in vitro, that ADAM10 targeting through shRNA and pharmacological (GI254023X) approaches reduced drastically mesothelioma cell migration and invasion, as well as for human mesothelioma cells treated with siRNA targeting ADAM10. Moreover, ADAM10 downregulation in murine mesothelioma cells significantly impairs MPM progression in vivo after intrapleural cell injection. We also demonstrate that ADAM10 sheddase downregulation decreases the production of a soluble N-cadherin fragment through membrane N-cadherin, which stimulated mesothelioma cell migration. Taken together, we demonstrate that ADAM10 is overexpressed in MPM and takes part to MPM progression through the generation of N-cadherin fragment that stimulates mesothelioma cell migration. ADAM10 inhibition is worth considering as a therapeutic perspective in mesothelioma context.}, } @article {pmid30648431, year = {2019}, author = {Harris, EJA and Musk, A and de Klerk, N and Reid, A and Franklin, P and Brims, FJH}, title = {Diagnosis of asbestos-related lung diseases.}, journal = {Expert review of respiratory medicine}, volume = {13}, number = {3}, pages = {241-249}, doi = {10.1080/17476348.2019.1568875}, pmid = {30648431}, issn = {1747-6356}, mesh = {Asbestos/*toxicity ; Asbestosis/diagnosis/diagnostic imaging ; Humans ; Lung Diseases/chemically induced/*diagnosis/diagnostic imaging ; Lung Neoplasms/chemically induced/diagnosis/diagnostic imaging ; Occupational Exposure ; Risk Assessment ; }, abstract = {The diagnosis of lung disease in asbestos-exposed individuals is a process that not only requires a detailed occupational and tobacco smoking history, but the correlation with physical signs, appropriate imaging, detailed lung function assessment and histology/cytology when required. Worldwide, the total quantity of asbestos mined is static, having decreased dramatically in developed countries but increased in countries where there is no restriction on mining: for example, Russia, China, Brazil, and Kazakhstan. The predominant diagnostic challenge in most cases of possible asbestos-related disease is the significant interval between exposure and development of the disease. Also challenging is the estimation of an individual's risk of disease, not least because asbestos-induced malignancy can be rapidly fatal, and, in the case of lung cancer, early detection can lead to treatment with curative intent. Areas covered: Discussion of quantitative asbestos exposure estimation and risk assessment, selection of the most appropriate imaging modality and frequency of imaging. Expert commentary: Consideration of the future for asbestos-related lung disease includes screening those at highest risk particularly in relation to ongoing mining operations and the management of in-situ asbestos. In the future, screening programs designed with estimation of risk of malignancy, based on quantitative estimates of asbestos exposure, and smoking history are indicated.}, } @article {pmid30642542, year = {2019}, author = {Wu, L and Dell'Anno, I and Lapidot, M and Sekido, Y and Chan, ML and Kohno, M and Serre-Beinier, V and Felley-Bosco, E and de Perrot, M}, title = {Progress of malignant mesothelioma research in basic science: A review of the 14th international conference of the international mesothelioma interest group (iMig2018).}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {127}, number = {}, pages = {138-145}, doi = {10.1016/j.lungcan.2018.11.034}, pmid = {30642542}, issn = {1872-8332}, mesh = {Animals ; Antineoplastic Agents/therapeutic use ; Congresses as Topic ; Humans ; *International Cooperation ; Lung Neoplasms/*metabolism/pathology/therapy ; Mesothelioma/*metabolism/pathology/therapy ; Mesothelioma, Malignant ; Molecular Targeted Therapy ; Pleural Neoplasms/*metabolism/pathology/therapy ; Public Opinion ; *Research ; Tumor Microenvironment ; }, abstract = {Here we summarize the most recent update of mesothelioma research in basic science presented at the 14[th] iMig2018 international conference. The symposium of basic science track mainly focused on the drivers of mesothelioma initiation and progression, molecular pathogenesis, and perspectives on potential therapeutic approaches. This review covers several promising fields including strategies efficiently inhibiting YAP/TAZ functions or their critical downstream targets, heparanase inhibitors, RAN depletion, and MIF/CD74 inhibitors that may be developed as novel therapeutic approaches. In addition, targeting mesothelioma stem cells by depleting M2-polarized macrophages in tumor microenvironment or blocking Tnfsf18 (GITRL)-GITR signalling might be translated into therapeutic modalities in mesothelioma treatment.}, } @article {pmid30629589, year = {2019}, author = {Chicco, D and Rovelli, C}, title = {Computational prediction of diagnosis and feature selection on mesothelioma patient health records.}, journal = {PloS one}, volume = {14}, number = {1}, pages = {e0208737}, pmid = {30629589}, issn = {1932-6203}, mesh = {Computational Biology/methods ; Female ; Health Records, Personal ; Humans ; *Machine Learning ; Male ; Mesothelioma/*diagnosis ; Regression Analysis ; }, abstract = {BACKGROUND: Mesothelioma is a lung cancer that kills thousands of people worldwide annually, especially those with exposure to asbestos. Diagnosis of mesothelioma in patients often requires time-consuming imaging techniques and biopsies. Machine learning can provide for a more effective, cheaper, and faster patient diagnosis and feature selection from clinical data in patient records.

METHODS AND FINDINGS: We analyzed a dataset of health records of 324 patients having mesothelioma symptoms from Turkey. The patients had prior asbestos exposure and displayed symptoms consistent with mesothelioma. We compared probabilistic neural network, perceptron-based neural network, random forest, one rule, and decision tree classifiers to predict diagnosis of the patient records. We measured classifiers' performance through standard confusion matrix scores such as Matthews correlation coefficient (MCC). Random forest outperformed all models tried, obtaining MCC = +0.37 on the complete imbalanced dataset and MCC = +0.64 on the under-sampled balanced dataset. We then employed random forest feature selection to identify the two most relevant dataset traits associated with mesothelioma: lung side and platelet count. These two risk factors resulted so predictive, that decision tree focusing on them achieved the second top accuracy on the complete dataset diagnosis prediction (MCC = +0.28), outperforming all other methods and even decision tree itself applied to all features.

CONCLUSIONS: Our results show that machine learning can predict diagnoses of patients having mesothelioma symptoms with high accuracy, sensitivity, and specificity, in few minutes. Additionally, random forest can efficiently select the most important features of this clinical dataset (lung side and platelet count) in few seconds. The importance of pleural plaques in lung sides and blood platelets in mesothelioma diagnosis indicates that physicians should focus on these two features when reading records of patients with mesothelioma symptoms. Moreover, doctors can exploit our machinery to predict patient diagnosis when only lung side and platelet data are available.}, } @article {pmid30623323, year = {2019}, author = {Taghizadeh, F and Jafari, AJ and Gholami, M and Kermani, M and Arfaeinia, H and Mohammadi, S and Dowlati, M and Shahsavani, A}, title = {Monitoring of airborne asbestos fibers in an urban ambient air of Shahryar City, Iran: levels, spatial distribution, seasonal variations, and health risk assessment.}, journal = {Environmental science and pollution research international}, volume = {26}, number = {7}, pages = {6450-6459}, pmid = {30623323}, issn = {1614-7499}, support = {31563//Environmental and occupational health center/ ; }, mesh = {Air Pollutants/*analysis ; Air Pollution/statistics & numerical data ; Asbestos/*analysis ; Cities ; Environmental Exposure/*statistics & numerical data ; Environmental Monitoring ; Humans ; Iran/epidemiology ; Lung Neoplasms/epidemiology ; Mesothelioma/epidemiology ; Mesothelioma, Malignant ; Microscopy, Phase-Contrast ; Risk Assessment ; Seasons ; }, abstract = {Asbestos, as with other pollutants in the air, has adverse effects on the health of human beings and animals. Today, the relationship between presence of asbestos fibers in the air breathed by humans and developing serious diseases such as lung cancer (asbestosis) and mesothelioma has been proven. This study was designed and conducted within the time period of August 2017 and June 2018 to determine the concentration of asbestos fiber in the ambient air of Shahryar City and to evaluate their health effects for the general population of the city. For this purpose, samples were taken from four points, and overall 32 air samples were taken along the year. The samples were then analyzed by the phase contrast microscopy (PCM) method. Also, to investigate the type of asbestos and for more accurate counting of fibers, SEM analysis was utilized. Finally, based on the EPA IRIS method, the health effects resulting from asbestos risks were also evaluated. The results of this study indicated that the mean annual concentration of asbestos fiber in the ambient air of Shahryar City was obtained as 0.0019 f/ml PCM and 0.0072 f/ml SEM. Furthermore, the most polluted point was S1 point (0.0119 -0.0026 f/ml, PCM), while the lowest concentration was related to S4 point (0.001 f/ml PCM-0.0021 f/ml SEM). The mean annual risk resulting from airborne asbestos fiber in the ambient air of Shahryar City for all samples was obtained as 1.72 × 10[-6] to 2.2 × 10[-4], which was higher than the recommended risk range in some points.}, } @article {pmid30622932, year = {2018}, author = {Lo Russo, G and Tessari, A and Capece, M and Galli, G and de Braud, F and Garassino, MC and Palmieri, D}, title = {MicroRNAs for the Diagnosis and Management of Malignant Pleural Mesothelioma: A Literature Review.}, journal = {Frontiers in oncology}, volume = {8}, number = {}, pages = {650}, pmid = {30622932}, issn = {2234-943X}, abstract = {Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor with a variable incidence among different countries. Occupational asbestos exposure is the most important etiological factor and a very long latency period is widely reported. In the early phase of the disease, clinical signs are absent or not specific. For this reason, the diagnosis is frequently achieved only in the advanced stages. The histopathological diagnosis per se is also very complex, and no known factor can predict the prognosis with certainty. Nonetheless, current survival rates remain very low, despite the use of standard treatments, which include surgery, chemotherapy and radiotherapy. The identification of new prognostic and/or diagnostic biomarkers, and the discovery of therapeutic targets is a priority and could lead to a real significant impact on the management of malignant pleural mesothelioma. In this scenario, the role of microRNAs is becoming increasingly relevant, with the promise of a quick translation in the current clinical practice. Despite the relative novelty of this field, the number of works and candidate microRNAs that are present in literature is striking. Unfortunately, to date the microRNAs with the most clinical relevance for MPM are still matter of debate, probably due to the variety of approaches, techniques, and collected samples. Although specific microRNAs (e.g., let-7, miR-15 and miR-16, miR-21, miR-34a, and the miR-200 family) have been reported several times from different groups, the heterogeneity of published data reinforces the need of more comprehensive and unified studies on this topic. In this review we collect and discuss the studies focused on the involvement of microRNAs in different aspects of MPM, from their biological role in tumorigenesis and progression, to their possible application as diagnostic, prognostic and predictive biomarkers. Lastly, we examine their potential value as for the design of therapeutic approaches that could benefit MPM patients.}, } @article {pmid30618090, year = {2019}, author = {Zha, L and Kitamura, Y and Kitamura, T and Liu, R and Shima, M and Kurumatani, N and Nakaya, T and Goji, J and Sobue, T}, title = {Population-based cohort study on health effects of asbestos exposure in Japan.}, journal = {Cancer science}, volume = {110}, number = {3}, pages = {1076-1084}, pmid = {30618090}, issn = {1349-7006}, support = {15H04774//Japan Society for the Promotion of Science KAKENHI/ ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Asbestos, Crocidolite/adverse effects ; Asbestos, Serpentine/adverse effects ; Cohort Studies ; Humans ; Japan/epidemiology ; Lung Neoplasms/epidemiology/etiology ; Male ; Mesothelioma/epidemiology/etiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Diseases/*epidemiology/*etiology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/epidemiology/etiology ; }, abstract = {Occupational asbestos exposure occurs in many workplaces and is a well-known cause of mesothelioma and lung cancer. However, the association between nonoccupational asbestos exposure and those diseases is not clearly described. The aim of this study was to investigate cause-specific mortality among the residents of Amagasaki, a city in Japan with many asbestos factories, and evaluate the potential excess mortality due to established and suspected asbestos-related diseases. The study population consisted of 143 929 residents in Amagasaki City before 1975 until 2002, aged 40 years or older on January 1, 2002. Follow-up was carried out from 2002 to 2015. Standardized mortality ratio (SMR) with its 95% confidence interval (CI) was calculated by sex, using the mortality rate of the Japanese population as reference. A total of 38 546 deaths (including 303 from mesothelioma and 2683 from lung cancer) were observed. The SMRs in the long-term residents' cohort were as follows: death due to all causes, 1.12 (95% CI, 1.10-1.13) in men and 1.07 (95% CI, 1.06-1.09) in women; lung cancer, 1.28 (95% CI, 1.23-1.34) in men and 1.23 (95% CI, 1.14-1.32) in women; and mesothelioma, 6.75 (95% CI, 5.83-7.78) in men and 14.99 (95% CI, 12.34-18.06) in women. These SMRs were significantly higher than expected. The increased SMR of mesothelioma suggests the impact of occupational asbestos exposure among men and nonoccupational asbestos exposure among women in the long-term residents' cohort. In addition, the high level of excess mortality from mesothelioma has persisted, despite the mixture of crocidolite and chrysotile no longer being used for three or four decades.}, } @article {pmid30609805, year = {2019}, author = {Turini, S and Bergandi, L and Gazzano, E and Prato, M and Aldieri, E}, title = {Epithelial to Mesenchymal Transition in Human Mesothelial Cells Exposed to Asbestos Fibers: Role of TGF-β as Mediator of Malignant Mesothelioma Development or Metastasis via EMT Event.}, journal = {International journal of molecular sciences}, volume = {20}, number = {1}, pages = {}, pmid = {30609805}, issn = {1422-0067}, mesh = {Antibodies/immunology ; Asbestos, Serpentine/*toxicity ; Cadherins/genetics/metabolism ; Cell Line ; Down-Regulation/drug effects ; Epithelial Cells/cytology/drug effects/metabolism ; Epithelial-Mesenchymal Transition/*drug effects ; Fibronectins/genetics/metabolism ; Humans ; Lung Neoplasms/chemically induced/pathology ; Matrix Metalloproteinase 2/genetics/metabolism ; Mesothelioma/chemically induced/pathology ; Mesothelioma, Malignant ; Smad Proteins/genetics/metabolism ; Snail Family Transcription Factors/genetics/metabolism ; Transforming Growth Factor beta/immunology/*metabolism ; Up-Regulation/drug effects ; Vimentin/genetics/metabolism ; Zinc Finger E-box-Binding Homeobox 1/genetics/metabolism ; beta Catenin/genetics/metabolism ; }, abstract = {Asbestos exposure increases the risk of asbestosis and malignant mesothelioma (MM). Both fibrosis and cancer have been correlated with the Epithelial to Mesenchymal Transition (EMT)-an event involved in fibrotic development and cancer progression. During EMT, epithelial cells acquire a mesenchymal phenotype by modulating some proteins. Different factors can induce EMT, but Transforming Growth Factor β (TGF-β) plays a crucial role in promoting EMT. In this work, we verified if EMT could be associated with MM development. We explored EMT in human mesothelial cells (MeT-5A) exposed to chrysotile asbestos: we demonstrated that asbestos induces EMT in MeT-5A cells by downregulating epithelial markers E-cadherin, β-catenin, and occludin, and contemporarily, by upregulating mesenchymal markers fibronectin, α-SMA, and vimentin, thus promoting EMT. In these cells, this mechanism is mediated by increased TGF-β secretion, which in turn downregulates E-cadherin and increases fibronectin. These events are reverted in the presence of TGF-β antibody, via a Small Mother Against Decapentaplegic (SMAD)-dependent pathway and its downstream effectors, such as Zinc finger protein SNAI1 (SNAIL-1), Twist-related protein (Twist), and Zinc Finger E-Box Binding Homeobox 1 (ZEB-1), which downregulate the E-cadherin gene. Since SNAIL-1, Twist, and ZEB-1 have been shown to be overexpressed in MM, these genes could be considered possible predictive or diagnostic markers of MM development.}, } @article {pmid30603603, year = {2019}, author = {Shehata, M and Zaid, F and Ottaviano, P and Shweihat, Y and Munn, N}, title = {Case report: Steroid responsive mesothelioma-related pleural effusion.}, journal = {Respiratory medicine case reports}, volume = {26}, number = {}, pages = {131-135}, pmid = {30603603}, issn = {2213-0071}, abstract = {Malignant pleural mesothelioma (MPM) is an asbestos-related tumor arising in the pleural cavity. Symptoms reflect extension of disease and include shortness of breath and chest pain. Unexplained pleural effusion and pleural pain in patients exposed to asbestos should raise the suspicion of MPM. The most common radiologic presentation is ipsilateral pleural effusion with or without pleural thickening or a mass. Thoracoscopic biopsy remains the most appropriate procedure for definitive diagnosis of mesothelioma. Despite advancement in diagnostic procedures and biomolecular research, this tumor nevertheless has poor prognosis. Mesothelioma remains a diagnostic and therapeutic challenge and is likely to remain one in the years to come. Here we present the first reported case of steroid treatment responsive pleural effusion in a 72 year-old-male that initially was misdiagnosed as rheumatoid related effusion. However, Pleuroscopy with biopsy revealed mesothelioma.}, } @article {pmid30596292, year = {2019}, author = {Ye, L and Ma, S and Robinson, BW and Creaney, J}, title = {Immunotherapy strategies for mesothelioma - the role of tumor specific neoantigens in a new era of precision medicine.}, journal = {Expert review of respiratory medicine}, volume = {13}, number = {2}, pages = {181-192}, doi = {10.1080/17476348.2019.1563488}, pmid = {30596292}, issn = {1747-6356}, mesh = {*Cancer Vaccines ; Humans ; Immunologic Factors/*therapeutic use ; Immunotherapy/*methods ; Lung Neoplasms/*drug therapy ; Mesothelioma/*drug therapy ; Mesothelioma, Malignant ; Precision Medicine/methods ; }, abstract = {Immunotherapy has long been considered a potential therapy for malignant mesothelioma and is currently being pursued as such. Some of the early phase clinical trials involving immunomodulators have demonstrated encouraging results and numerous clinical trials are underway to further investigate this treatment approach in various treatment settings and larger patient cohorts. Areas covered: This review summarizes the current and emerging clinical evidence for checkpoint blockade and other immunotherapeutic strategies in mesothelioma. The mesothelioma tumor immune microenvironment and mutational landscape are also discussed, including their impact on treatment strategies. We also provide an evaluation of the current evidence for neoantigen targeted personalized immunotherapy. Expert opinion: Immune checkpoint inhibitors work by unleashing the host immune response against probable neoantigens. Despite impressive activity in a small subset of patients and the potential for prolonged responses, most patients experience treatment failure. Neoantigen vaccines provide a potential complementary therapeutic strategy by increasing the immunogenic antigen load, which can lead to an increased tumor specific immune response. Further research is needed explore this treatment option in mesothelioma and technological advances are required to translate this concept into clinical practice.}, } @article {pmid30594459, year = {2019}, author = {McGehee, E and Gerber, DE and Reisch, J and Dowell, JE}, title = {Treatment and Outcomes of Primary Pericardial Mesothelioma: A Contemporary Review of 103 Published Cases.}, journal = {Clinical lung cancer}, volume = {20}, number = {2}, pages = {e152-e157}, doi = {10.1016/j.cllc.2018.11.008}, pmid = {30594459}, issn = {1938-0690}, support = {K24 CA201543/CA/NCI NIH HHS/United States ; UL1 TR001105/TR/NCATS NIH HHS/United States ; }, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Asbestos/adverse effects ; Environmental Exposure/adverse effects ; Heart Neoplasms/mortality/*therapy ; Humans ; Neoplasms, Mesothelial/mortality/*therapy ; Pemetrexed/*therapeutic use ; Pericardium ; Platinum/*therapeutic use ; Risk Factors ; Survival Analysis ; Treatment Outcome ; }, abstract = {Primary pericardial mesothelioma (PPM) is a rare cancer for which there is no consensus on treatment. We evaluated and summarized a large contemporary population of published PPM cases to characterize risk factors, treatment patterns, and clinical outcomes. Using Ovid and PubMed, literature published from 2000 through 2016 was searched using the terms "primary pericardial mesothelioma," "pericardial mesothelioma," and "malignant pericardial mesothelioma." We identified 6 case series and 84 case reports for a total of 103 PPM cases published from 2000 through 2016. The median age at diagnosis was 55 years, and the median overall survival was 6 months. In univariate analyses of clinical characteristics including gender, asbestos exposure, tobacco use, prior radiation exposure, histologic subtype, and metastasis and/or mediastinal spread, only the presence of metastasis and/or mediastinal spread was a significant predictor of decreased survival (P = .015). Surgery did not provide a statistically significant survival benefit (P = .12). A survival benefit was noted in those who received chemotherapy (median survival, 13 months vs. 0.5 months, P = .002), specifically chemotherapy with a platinum agent with or without pemetrexed. In multivariate analysis, only the receipt of chemotherapy was associated with improved survival. PPM remains a rare and poorly understood malignancy with unclear etiology and a poor prognosis. In this retrospective systematic review, a survival benefit was seen in patients who received chemotherapy.}, } @article {pmid30594195, year = {2018}, author = {Merlo, DF and Bruzzone, M and Bruzzi, P and Garrone, E and Puntoni, R and Maiorana, L and Ceppi, M}, title = {Mortality among workers exposed to asbestos at the shipyard of Genoa, Italy: a 55 years follow-up.}, journal = {Environmental health : a global access science source}, volume = {17}, number = {1}, pages = {94}, pmid = {30594195}, issn = {1476-069X}, mesh = {Adult ; Air Pollutants, Occupational/*adverse effects ; Asbestos/*adverse effects ; Follow-Up Studies ; Humans ; Italy/epidemiology ; Neoplasms/*mortality ; Occupational Diseases/*mortality ; Occupational Exposure/*adverse effects ; Respiratory Tract Diseases/*mortality ; *Ships ; Young Adult ; }, abstract = {BACKGROUND: Exposure to asbestos remains a global issue due to its massive use in the twentieth century and its long environmental persistence. Exposure to asbestos still occurs during dismantling of ships and vessels, buildings renovation, mining operations, and is reported in developing countries. Current estimate report exposure of hundreds of million people in occupational settings in countries where its use remains unregulated.

METHODS: We conducted a historical prospective cohort mortality study aimed at estimating mortality from specific causes, the temporal changes of pleural and lung cancer mortality, and the attributable fraction (AF) of lung cancer deaths following asbestos exposure. The study included 3984 shipyard workers employed at the shipyard of Genoa, Italy, between 1960 and 1981 and followed up to December 2014. Standardized Mortality Ratios (SMR) and their 95% confidence intervals (95%CI) were computed.

RESULTS: Overall deaths recorded were 3331 (83.6%). Excess mortality was observed for all cancers (SMR = 127, 95%CI:120-134), pleural mesothelioma (575, 469-697), cancers of the larynx (183, 134-244) and of the lung (154, 139-170), and for respiratory tract diseases (127, 114-141), including asbestosis (2277, 1525-3270). Ninety out of 399 deaths (22.6%) from lung cancer were attributed to asbestos exposure. The estimated lung cancer AF was 49.3% in workers with the highest SMR for pleural cancer. Median latency times for pleural and lung cancer were 42.8 years (minimum latency: 9.3 years) and 38.7 years (minimum latency: 6 years). The peak of mesothelioma incidence, expected in Italy in the period 2015-2024, was confirmed.

CONCLUSIONS: The long follow-up period of our study allowed the detection of a substantial disease burden following asbestos exposure. These findings support the urgent need for the prevention of asbestos related diseases through the implementation of asbestos ban worldwide, including those countries where asbestos is still mined, manufactured and used.}, } @article {pmid30567579, year = {2018}, author = {Xu, R and Barg, FK and Emmett, EA and Wiebe, DJ and Hwang, WT}, title = {Association between mesothelioma and non-occupational asbestos exposure: systematic review and meta-analysis.}, journal = {Environmental health : a global access science source}, volume = {17}, number = {1}, pages = {90}, pmid = {30567579}, issn = {1476-069X}, support = {P30 ES013508/ES/NIEHS NIH HHS/United States ; P42ES023720/ES/NIEHS NIH HHS/United States ; }, mesh = {Asbestos/*adverse effects ; Case-Control Studies ; Cohort Studies ; Environmental Exposure/*adverse effects ; Humans ; Mesothelioma/*epidemiology ; Risk Factors ; }, abstract = {BACKGROUND: The risk of mesothelioma has been shown to be associated with exposure to asbestos fibers. Most of the existing literature focuses on occupational exposure; however, non-occupational asbestos exposure has also been identified as an important risk factor.

OBJECTIVE: To estimate the association between mesothelioma and non-occupational asbestos exposure, and evaluate control recruitment and exposure measurement methods.

METHODS: A systematic literature review was conducted to identify case-control (CC) and cohort studies that examined the association between mesothelioma and non-occupational exposure to asbestos, including neighborhood, domestic, and household exposure. Meta-analysis was performed to estimate a summary relative risk estimate (SRRE) and 95% confidence interval using random-effects models. Subgroup analyses were also conducted by exposure type, gender, region, and fiber type.

RESULTS: Twenty CC and 7 cohort studies were selected. Controls in CC studies were selected from the general population (55%), hospital records (18%), cancer registry (23%) and a combination of population and hospital records (5%). Multiple methods were used to measure neighborhood exposure (e.g., linear distance and direction of residence from an asbestos factory), domestic (e.g., whether living with an asbestos worker) and household exposure (e.g., whether involved in asbestos-containing home improvement projects). Primary meta-analyses suggested a SRRE of mesothelioma of 5.33 (95%CI: 2.53, 11.23) from neighborhood exposure, 4.31 (95%CI, 2.58, 7.20) from domestic exposure, and 2.41 (95%CI, 1.30, 4.48) from household exposure with large I[2] statistics ranging from 83-99%.

CONCLUSIONS: Non-occupational asbestos exposure is significantly associated with an elevated risk of mesothelioma. Funnel plots indicated a potential of publication bias. Some SRREs should be interpreted with cautions because of high between-studies heterogeneity.}, } @article {pmid30563645, year = {2018}, author = {Rogers, AJ}, title = {Exposures estimates of the Wittenoom mining workforce and town residents - Implications associated with risk estimation for persons exposed to asbestiform riebeckite.}, journal = {Toxicology and applied pharmacology}, volume = {361}, number = {}, pages = {168-170}, doi = {10.1016/j.taap.2018.06.032}, pmid = {30563645}, issn = {1096-0333}, mesh = {Adult ; Asbestos/analysis ; Asbestos, Crocidolite/analysis/*toxicity ; Australia/epidemiology ; Child ; Dust/analysis ; Environmental Exposure/*statistics & numerical data ; Female ; Humans ; Industry ; Inhalation Exposure/*analysis ; Lung Neoplasms/epidemiology/etiology ; Male ; Mesothelioma/epidemiology/etiology ; *Mining ; Occupational Exposure/*statistics & numerical data ; Risk Assessment ; Workforce ; }, abstract = {The mining of crocidolite at Wittenoom from 1943 to 1966 is infamous due to the adverse health outcomes in the mining and milling workforce and the non-mining residents and families. Proportional latency risk analysis provided estimates that 6% of the mine workforce along with 1.9% of women and 1.1% of children residents who were environmentally exposed, have or will die from mesothelioma. The absence of environmental exposure data relevant to the period restricts the extrapolation of these historical risk outcomes being applied to the low level exposures from natural contaminant crocidolite and other amphibole fibres experienced in contemporary mining practices in the Pilbara region.}, } @article {pmid30561515, year = {2019}, author = {Oddone, E and Terracini, B and Mirabelli, D and Mensi, C and Consonni, D and Barone-Adesi, F}, title = {Comment on: Malignant mesothelioma diagnosed at a younger age is associated with heavier asbestos exposure.}, journal = {Carcinogenesis}, volume = {40}, number = {3}, pages = {488-489}, doi = {10.1093/carcin/bgy179}, pmid = {30561515}, issn = {1460-2180}, mesh = {*Asbestos ; Humans ; *Lung Neoplasms ; *Mesothelioma ; }, } @article {pmid30558734, year = {2019}, author = {Kai, Y and Tsutani, Y and Ito, M and Mimura, T and Miyata, Y and Okada, M}, title = {Metachronous Lung Cancer After Pleurectomy/Decortication.}, journal = {The Annals of thoracic surgery}, volume = {107}, number = {1}, pages = {e1-e3}, doi = {10.1016/j.athoracsur.2018.05.087}, pmid = {30558734}, issn = {1552-6259}, abstract = {Pleurectomy/decortication is a surgical procedure for malignant pleural mesothelioma (MPM) and has been proposed as an alternative to extrapleural pneumonectomy. We report a second primary lung cancer developing after pleurectomy/decortication for MPM. A 59-year-old man was diagnosed with MPM on the right side and underwent pleurectomy/decortication. Follow-up computed tomography detected a nodule in the right upper lobe that was diagnosed as adenocarcinoma by wedge resection. Lung cancer and MPM are associated with asbestos exposure. However, predicting lung cancer after treatment for MPM is difficult. Careful follow-up of the spared lung is necessary for detecting second primary lung cancer or MPM recurrence.}, } @article {pmid30557225, year = {2019}, author = {Schnatter, AR and Wojcik, NC and Jorgensen, G}, title = {Mortality Update of a Cohort of Canadian Petroleum Workers.}, journal = {Journal of occupational and environmental medicine}, volume = {61}, number = {3}, pages = {225-238}, pmid = {30557225}, issn = {1536-5948}, mesh = {Adult ; Canada/epidemiology ; Cause of Death ; *Extraction and Processing Industry ; Female ; Humans ; Lung Neoplasms/*epidemiology/*mortality ; Male ; Mesothelioma/*epidemiology/*mortality ; Mesothelioma, Malignant ; Occupational Diseases/*epidemiology/*mortality ; *Occupational Exposure ; *Petroleum ; }, abstract = {OBJECTIVE: This study updates the mortality experience of over 25,000 workers in a large Canadian petroleum company through December 31, 2006.

METHODS: Standardized mortality ratios were generated for all-cause and specific cause mortality.

RESULTS: All cause and all cancer mortality were favorable compared with the general Canadian population. Cancers of previous interest were largely consistent with expectation. There is a continuing excess of mesothelioma, which is of similar magnitude as the previous update, although based on larger numbers. This excess is mostly attributable to men who died in their 50s and 60s and who worked in the refining sector.

CONCLUSION: Most causes of death show mortality rates lower than the Canadian general population. Given the excess of mesothelioma observed, this study supports ongoing vigilance in asbestos exposure control programs, as refineries continue to remove asbestos from their facilities.}, } @article {pmid30545133, year = {2018}, author = {Wörthmüller, J and Oberson, A and Salicio, V and Blum, W and Schwaller, B}, title = {Calretinin Functions in Malignant Mesothelioma Cells Cannot Be Replaced by the Closely Related Ca[2+]-Binding Proteins Calbindin-D28k and Parvalbumin.}, journal = {International journal of molecular sciences}, volume = {19}, number = {12}, pages = {}, pmid = {30545133}, issn = {1422-0067}, support = {130680, 139226, 147697/1//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung/ ; }, mesh = {Calbindin 1/*metabolism ; Calbindin 2/*metabolism ; Cell Line, Tumor ; Cell Proliferation ; Cell Survival ; Clone Cells ; Down-Regulation ; Focal Adhesion Protein-Tyrosine Kinases/metabolism ; Focal Adhesions/metabolism ; Green Fluorescent Proteins/metabolism ; Humans ; Lentivirus/metabolism ; Lung Neoplasms/*metabolism ; Mesothelioma/*metabolism ; Mesothelioma, Malignant ; Parvalbumins/*metabolism ; Phenotype ; }, abstract = {Calretinin (CR; CALB2) belonging to the family of EF-hand Ca[2+]-binding proteins (CaBP) is widely used as a positive marker for the identification of human malignant mesothelioma (MM) and functionally was suggested to play a critical role during carcinogenesis of this highly aggressive asbestos-associated neoplasm. Increasing evidence suggests that CR not only acts as a prototypical Ca[2+] buffer protein, i.e., limiting the amplitude of Ca[2+] signals but also as a Ca[2+] sensor. No studies have yet investigated whether other closely related CaBPs might serve as substitutes for CR's functions(s) in MM cells. Genetically modified MM cell lines with medium (MSTO-211H and ZL5) or low (SPC111) endogenous CR expression levels were generated that overexpress either CR's closest homologue calbindin-D28k (CB) or parvalbumin (PV), the latter considered as a "pure" Ca[2+] buffer protein. After lentiviral shCALB2-mediated CR downregulation, in both MSTO-211H and ZL5 cells expressing CB or PV, the CR deficiency-mediated increase in cell death was not prevented by CB or PV. With respect to proliferation and cell morphology of SPC111 cells, CB was able to substitute for CR, but not for CR's other functions to promote cell migration or invasion. In conclusion, CR has a likely unique role in MM that cannot be substituted by "similar" CaBPs.}, } @article {pmid30534997, year = {2019}, author = {Boffetta, P and Righi, L and Ciocan, C and Pelucchi, C and La Vecchia, C and Romano, C and Papotti, M and Pira, E}, title = {Reply to letters to the editor by Brentisci et al. and Consonni and Mensi.}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {30}, number = {2}, pages = {341}, doi = {10.1093/annonc/mdy523}, pmid = {30534997}, issn = {1569-8041}, mesh = {*Asbestos ; Humans ; Italy ; *Lung Neoplasms ; *Mesothelioma ; Textiles ; Tumor Suppressor Proteins ; Ubiquitin Thiolesterase ; }, } @article {pmid30533375, year = {2019}, author = {Yamazoe, M and Tomioka, H and Kamada, T and Kaneko, M and Katsuyama, E}, title = {Simultaneous presence of lung adenocarcinoma and malignant pleural mesothelioma: A case report.}, journal = {Respiratory medicine case reports}, volume = {26}, number = {}, pages = {45-49}, pmid = {30533375}, issn = {2213-0071}, abstract = {The co-presence of malignant pleural mesothelioma (MPM) and lung cancer is rare. We report a 70-year-old male with exposure to asbestos. Chest computed tomography revealed a right mediastinal mass combined with an enlarged ipsilateral lymph node and left pleural effusion. Transbronchial lung biopsy revealed lung adenocarcinoma. Thoracoscopic examination revealed multiple left pleural nodules, leading to the diagnosis of MPM. Despite aggressive anticancer drug therapy, he expired due to disease progression 2.5 years after diagnosis. Autopsy confirmed an epithelioid MPM in the left pleura. MPM comorbidity in patients diagnosed with lung cancer should be considered, especially in those exposed to asbestos.}, } @article {pmid30530573, year = {2018}, author = {Lee, LJ and Lin, CK and Pan, CH and Cheng, Y and Chang, YY and Liou, SH and Wang, JD}, title = {Clustering of malignant pleural mesothelioma in asbestos factories: a subgroup analysis in a 29-year follow-up study to identify high-risk industries in Taiwan.}, journal = {BMJ open}, volume = {8}, number = {12}, pages = {e021063}, pmid = {30530573}, issn = {2044-6055}, mesh = {Asbestos/*adverse effects ; Cluster Analysis ; Cohort Studies ; Cross-Sectional Studies ; Female ; Follow-Up Studies ; Humans ; Male ; Manufacturing and Industrial Facilities/*statistics & numerical data ; Mesothelioma/*epidemiology/etiology ; Occupational Diseases/*epidemiology/etiology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*epidemiology/etiology ; Retrospective Studies ; Risk ; Taiwan ; }, abstract = {OBJECTIVE: Exposure to asbestos is the major cause for malignant pleural mesothelioma (MPM), but the causal link of individual cases is difficult to establish for lack of exposure information and long disease latency.

METHODS: We established a retrospective cohort of workers employed in asbestos industries during the period of 1950-1989 and the occurrence of MPM during the period of 1980-2009 was examined with the Taiwan Cancer Registry. Estimated rate ratios (eRRs) were computed for each factory where any case of MPM was diagnosed by assuming Poisson distribution with a minimal latency of 20 years.

RESULTS: A total of 18 MPM (17 males, 1 female) in eight factories were found. The incidence rate of MPM for the eight factories was 18.0 per million, ranging from 6.2 per million (military factory) to 268.2 per million (asbestos cement). We observed significantly increased risks for MPM in asbestos cement, thermal insulation and shipbuilding industries, with eRR (genders combined) of 113.6, 87.5 and 15.8, respectively. The sensitivity analyses considering latency showed similar findings in latency ≥30 years, and the shipbuilding industry presented a significant eRR given a latency ≥40 years. The gender-specific eRR showed similar results in men, but high eRR of 729.6 was observed in an asbestos cement factory where a female MPM was diagnosed.

CONCLUSIONS: This nationwide study in Taiwan comprehensively shows that different asbestos manufacturing processes, including asbestos cement, thermal insulation and shipbuilding industries, were at significantly increased risks for MPM. We recommend to establish a medical screening programme for workers previously exposed to asbestos to identify MPM and other asbestos-related diseases at an earlier stage.}, } @article {pmid30527173, year = {2018}, author = {Serio, G and Vimercati, L and Pennella, A and Gentile, M and Cavone, D and Buonadonna, AL and Scattone, A and Fortarezza, F and De Palma, A and Marzullo, A}, title = {Genomic changes of chromosomes 8p23.1 and 1q21: Novel mutations in malignant mesothelioma.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {126}, number = {}, pages = {106-111}, doi = {10.1016/j.lungcan.2018.10.012}, pmid = {30527173}, issn = {1872-8332}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Chromosome Aberrations ; Chromosomes, Human, Pair 1/*genetics ; Chromosomes, Human, Pair 8/*genetics ; Comparative Genomic Hybridization ; Female ; Humans ; Lung Neoplasms/*genetics/pathology ; Male ; Mesothelioma/*genetics/pathology ; Middle Aged ; *Mutation ; Ubiquitin-Conjugating Enzymes/genetics ; }, abstract = {INTRODUCTION: Malignant mesothelioma is an aggressive malignancy of the thoracic cavity caused by prior asbestos exposure. In the peritoneum the mesothelioma is an extremely rare condition. In the present preliminary study, high-resolution array-comparative genomic hybridization (a-CGH) was performed to identify genetic imbalances in a series of malignant peritoneal mesothelioma cases.

MATERIALS AND METHODS: Between 1990 and 2008, among the cases recorded in the Apulia Mesothelioma Register, we found 22 peritoneal mesothelioma cases. CGH-array was performed on samples from all patients.

RESULTS: The CGH-array analysis revealed multiple chromosomal imbalances. Interestingly, deletion at 8p23.1 was observed in 12 cases. Furthermore, another novel deletion at 1q21 was present in 11. Often, 1q21 and 8p23.1 losses were present in the same patient (7 cases). Losses of BAP1 and CDKN2A loci were not detected.

DISCUSSION: The region at 8p23.1 contains the beta-defensin gene cluster (DEF) and 1q21 contains ubiquitin conjugating enzyme E2 (UBE2Q1). We hypotesized that the loss of function of ubiquitination, as well as of the defensins, could play an important role in the initial development and subsequent progression of mesothelioma.}, } @article {pmid30518402, year = {2018}, author = {Chee, J and Watson, MW and Chopra, A and Nguyen, B and Cook, AM and Creaney, J and Lesterhuis, WJ and Robinson, BW and Lee, YCG and Nowak, AK and Lake, RA and McDonnell, AM}, title = {Tumour associated lymphocytes in the pleural effusions of patients with mesothelioma express high levels of inhibitory receptors.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {864}, pmid = {30518402}, issn = {1756-0500}, support = {CA150787//U.S. Department of Defense/ ; }, mesh = {Aged ; Aged, 80 and over ; Humans ; Lung Neoplasms/blood/*immunology ; Mesothelioma/blood/*immunology ; Mesothelioma, Malignant ; Middle Aged ; Pleural Effusion/blood/*immunology ; Receptors, Antigen, T-Cell/metabolism ; Receptors, Cell Surface/*metabolism ; T-Lymphocytes/*immunology ; }, abstract = {OBJECTIVE: Pleural effusion (PE) is a common feature of malignant pleural mesothelioma. These effusions typically contain lymphocytes and malignant cells. We postulated that the PE would be a source of lymphocytes for analysis of tumor immune milieu. The aim of this study was to compare the phenotype and T cell receptor usage of pleural effusion T cells with paired concurrently drawn peripheral blood lymphocytes. We used multi-parameter flow cytometry and high-throughput T cell receptor sequencing to analyse peripheral blood and pleural effusion mononuclear cells.

RESULTS: Both CD8[+] and CD4[+] T cells from effusion showed increased expression of T cell inhibitory receptors PD-1, LAG-3 and Tim-3 compared to blood. Comprehensive T cell receptor sequencing on one of the patients showed a discordant distribution of clonotypes in the antigen-experienced (PD-1[+]) compartment between effusion and blood, suggesting an enrichment of antigen specific clonotypes in the effusion, with potential as an immunological response biomarker.}, } @article {pmid30506035, year = {2018}, author = {Okita, R and Nojima, Y and Saisho, S and Shimizu, K and Shirai, R and Kanomata, N and Oka, M and Nakata, M}, title = {Deciduoid type malignant pleural mesothelioma: a case report.}, journal = {AME case reports}, volume = {2}, number = {}, pages = {43}, pmid = {30506035}, issn = {2523-1995}, abstract = {Here, we report a patient with deciduoid type malignant pleural mesothelioma (MPM), which rapidly progressed. A 55-year-old man who might have been exposed to asbestos a few decades ago had severe back pain. The chest X-ray scanning and computed tomography (CT) revealed pleural thickness on his right thoracic space, without the presence of a lung mass. A pleural biopsy was performed and the patient was histologically diagnosed with deciduoid type MPM. Although he received two cycles of chemotherapy, his disease rapidly progressed and he died within two months of the diagnosis of deciduoid type MPM.}, } @article {pmid30501113, year = {2018}, author = {Izquierdo-Sánchez, V and Muñiz-Hernández, S and Vázquez-Becerra, H and Pacheco-Yepez, J and Romero-Piña, ME and Arrieta, O and Medina, LA}, title = {Biodistribution and Tumor Uptake of [67]Ga-Nimotuzumab in a Malignant Pleural Mesothelioma Xenograft.}, journal = {Molecules (Basel, Switzerland)}, volume = {23}, number = {12}, pages = {}, pmid = {30501113}, issn = {1420-3049}, support = {PAPIIT IN-225014, IN209916//Universidad Nacional Autónoma de México/ ; 154557//Consejo Nacional de Ciencia y Tecnología/ ; (017/027/IBI)(CEI/1147/17)//Instituto Nacional de Cancerología/ ; }, mesh = {Animals ; Antibodies, Monoclonal, Humanized/*pharmacokinetics ; Cell Line, Tumor ; Fluorodeoxyglucose F18/chemistry ; Gallium Radioisotopes/*pharmacokinetics ; Humans ; Imaging, Three-Dimensional ; Liver/metabolism ; Lung Neoplasms/diagnostic imaging/*metabolism ; Male ; Mesothelioma/diagnostic imaging/*metabolism ; Mesothelioma, Malignant ; Mice, Nude ; Pleural Neoplasms/diagnostic imaging/*metabolism ; Positron Emission Tomography Computed Tomography ; Tissue Distribution ; Tomography, Emission-Computed, Single-Photon ; *Xenograft Model Antitumor Assays ; }, abstract = {Malignant pleural mesothelioma (MPM) is the most common tumor of the pulmonary pleura. It is a rare and aggressive malignancy, generally associated with continuous occupational exposure to asbestos. Only a multimodal-approach to treatment, based on surgical resection, chemotherapy and/or radiation, has shown some benefits. However, the survival rate remains low. Nimotuzumab (h-R3), an anti-EGFR (epidermal growth factor receptor) humanized antibody, is proposed as a promising agent for the treatment of MPM. The aim of this research was to implement a procedure for nimotuzumab radiolabeling to evaluate its biodistribution and affinity for EGF (epidermal growth factor) receptors present in a mesothelioma xenograft. Nimotuzumab was radiolabeled with [67]Ga; radiolabel efficiency, radiochemical purity, serum stability, and biodistribution were evaluated. Biodistribution and tumor uptake imaging studies by microSPECT/CT in mesothelioma xenografts revealed constant nimotuzumab uptake at the tumor site during the first 48 h after drug administration. In vivo studies using MPM xenografts showed a significant uptake of this radioimmunoconjugate, which illustrates its potential as a biomarker that could promote its theranostic use in patients with MPM.}, } @article {pmid30513236, year = {2022}, author = {Till, JE and Beck, HL and Boice, JD and Mohler, HJ and Mumma, MT and Aanenson, JW and Grogan, HA}, title = {Asbestos exposure and mesothelioma mortality among atomic veterans.}, journal = {International journal of radiation biology}, volume = {98}, number = {4}, pages = {781-785}, doi = {10.1080/09553002.2018.1551641}, pmid = {30513236}, issn = {1362-3095}, support = {U01 CA137026/CA/NCI NIH HHS/United States ; }, mesh = {*Asbestos/adverse effects ; Cohort Studies ; Humans ; *Lung Neoplasms/etiology ; Male ; *Mesothelioma/complications ; *Occupational Diseases/etiology ; *Occupational Exposure/adverse effects ; *Veterans ; }, abstract = {BACKGROUND: The United States (U.S.) conducted 230 above-ground atmospheric nuclear weapons tests between 1945 and 1962 involving over 250,000 military personnel. This is the first quantitative assessment of asbestos-related mesothelioma, including cancers of the pleura and peritoneum, among military personnel who participated in above-ground nuclear weapons testing.

METHODS: Approximately 114,000 atomic veterans were selected for an epidemiological study because they were in one of eight series of weapons tests that were associated with somewhat higher personnel exposures than the other tests and because they have been previously studied. We were able to categorize specific jobs into potential for asbestos exposure based on a detailed database of the military activities of the atomic veterans. Standardized mortality ratios (SMR) were calculated by service, rank (officer/enlisted) and ratings (occupation code and work location aboard ship) after 65 years of follow-up.

RESULTS: Mesothelioma deaths were significantly increased overall (SMR 1.56; 95% CI 1.32-1.82; n = 153). This increase was seen only among those serving in the PPG (SMR 1.97; 95% CI 1.65-2.34; n = 134), enlisted men (SMR 1.81; 95% CI 1.53-2.13; n = 145), and the 70,309 navy personnel (SMR 2.15; 95% CI 1.80-2.56; n = 130). No increased mortality rates were seen among the other services: army (SMR 0.45), air force (SMR 0.85), or marines (SMR 0.75). Job categories with the highest potential for asbestos exposure (machinist's mates, boiler technicians, water tender, pipe fitters, and fireman) had an of SMR 6.47. Job categories with lower potential (SMR =1.35) or no potential (SMR =1.28) for asbestos exposure had non-significantly elevated mesothelioma mortality.

CONCLUSIONS: The large excess of mesothelioma deaths seen among atomic veterans was explained by asbestos exposure among enlisted naval personnel. The sources of exposure were determined to be on navy ships in areas (or with materials) with known asbestos content. No excess of mesothelioma was observed in other services or among naval personnel with minimal exposure to asbestos in this low-dose radiation exposed cohort.}, } @article {pmid30500290, year = {2019}, author = {Regragui, M and Guebessi, NB}, title = {Primary Malignant Deciduoid Mesothelioma: A Challenging Diagnosis.}, journal = {Archives of pathology & laboratory medicine}, volume = {143}, number = {4}, pages = {531-533}, doi = {10.5858/arpa.2017-0461-RS}, pmid = {30500290}, issn = {1543-2165}, mesh = {Decidua/*pathology ; Female ; Humans ; Lung Neoplasms/*pathology ; Mesothelioma/*pathology ; Mesothelioma, Malignant ; Peritoneal Neoplasms/*pathology ; }, abstract = {Primary malignant deciduoid mesothelioma is a rare subtype of epithelioid mesothelioma that was first described in the peritoneum in young women without a history of asbestos exposure. It was thought to be a distinct clinicopathologic entity with ominous prognosis; recent studies have better characterized this entity. On morphology, primary malignant deciduoid mesothelioma is characterized by cytomorphologic features resembling decidualized tissue. Pleomorphism is variable. The immunoprofile is similar to other epithelioid mesotheliomas. The prognosis is the same as other epithelioid mesotheliomas and seems to depend on histological grade.}, } @article {pmid30489434, year = {2019}, author = {Dournes, G and Dubois, A and Benlala, I and Lacourt, A and Paris, C and Gislard, A and Clin, B and Pairon, JC and Baldacci, F and Laurent, F}, title = {3-Dimensional Quantification of Composite Pleural Plaque Volume in Patients Exposed to Asbestos Using High-resolution Computed Tomography: A Validation Study.}, journal = {Journal of thoracic imaging}, volume = {34}, number = {5}, pages = {320-325}, doi = {10.1097/RTI.0000000000000377}, pmid = {30489434}, issn = {1536-0237}, mesh = {Aged ; Asbestos/*adverse effects ; Female ; Humans ; Imaging, Three-Dimensional/*methods ; Male ; Plaque, Atherosclerotic/*diagnostic imaging ; Pleural Diseases/*chemically induced/*diagnostic imaging ; Reproducibility of Results ; Retrospective Studies ; Tomography, X-Ray Computed/*methods ; }, abstract = {RATIONALE: As pleural plaque has been reported as a risk factor in the occurrence of lung cancer and mesothelioma, a reproducible and precise method of measurement of pleural plaque volume (PPV) is needed to further describe these relationships. The aim of the study was to assess the reproducibility of a 3-dimensional computed tomography (3D-CT) volumetric analysis of PPV in patients with occupational exposure to asbestos.

MATERIAL AND METHODS: A total of 28 patients were retrospectively randomly selected from the multicenter APEXS (Asbestos Post Exposure Survey) study, which was held between 2003 and 2005. All patients underwent a 3D-CT scan. Two readers specialized in chest radiology completed the 3D semiautomated quantification of lung volume using dedicated software. They also had to categorize the visual extent of pleural plaque in terms of thickness and circumference. Reproducibility of the continuous PPV variable was assessed using the intraclass correlation coefficient (ICC) and Bland-Altman analysis. Reproducibility of categorical variables was assessed using the κ test.

RESULTS: Intraobserver reproducibility of PPV was almost perfect (ICC=0.98 [95% interval: 0.97-0.99]), and interobserver reproducibility was very good (ICC=0.93 [0.88-0.97]). At Bland-Altman analysis, the mean differences were 0.1 (limit of agreement: -11.0 to 11.2) and 3.7 cc (-17.8 to 25.2), respectively. Visual analysis of both plaque in terms of thickness and circumference were fair to moderate, with κ values ranging from 0.30 to 0.60.

CONCLUSIONS: 3D semiautomatic quantification of PPV is feasible and reproducible using CT in patients with occupational exposure to asbestos. PPV measurement may be useful to correlate with other asbestos-related disease outcomes and prognosis.}, } @article {pmid30479777, year = {2018}, author = {Park, S and Park, J and Lee, E and Eom, H and Shin, MY and Kim, J and Kang, D and Lee, S}, title = {Ovarian cancer in a former asbestos textile factory worker: a case report.}, journal = {Annals of occupational and environmental medicine}, volume = {30}, number = {}, pages = {65}, pmid = {30479777}, issn = {2052-4374}, abstract = {BACKGROUND: The International Agency for Research on Cancer (IARC) defined that asbestos is a group 1 substance that causes lung cancer, mesothelioma (pleura and peritoneum), laryngeal cancer, and ovarian cancer in humans. Many studies on lung cancer, and mesothelioma caused by asbestos exposure have been conducted, but there was no case report of ovarian cancer due to asbestos exposure in Korea. We describe a case of ovarian cancer caused by asbestos exposure in a worker who worked at an asbestos textile factory for 3 years and 7 months in the late 1970s.

CASE PRESENTATION: A 57-year-old woman visited the hospital because she had difficulty urinating. Ovarian cancer was suspected in radiologic examination, and exploratory laparotomy was performed. She was diagnosed with epithelial ovarian cancer. The patient did not undergo postoperative chemotherapy and recovered. She joined the asbestos factory in March 1976 and engaged in asbestos textile twisting and spinning for 1 year, 2 years and 7 months respectively. In addition, she lived near the asbestos factory for more than 20 years. There was no other specificity or family history.

CONCLUSION: Considering the patient's occupational and environmental history, it is estimated that she had been exposed to asbestos significantly, so we determined that ovarian cancer in the patient is highly correlated with the occupational exposure of asbestos and environmental exposure is a possible cause as well. Social devices are needed to prevent further exposure to asbestos. It is also necessary to recognize that ovarian cancer can occur in workers who have previously been exposed to asbestos, and the education and social compensation for those workers are needed.}, } @article {pmid30479770, year = {2019}, author = {Tlotleng, N and Sidwell Wilson, K and Naicker, N and Koegelenberg, CF and Rees, D and Phillips, JI}, title = {The significance of non-occupational asbestos exposure in women with mesothelioma.}, journal = {Respirology case reports}, volume = {7}, number = {1}, pages = {e00386}, pmid = {30479770}, issn = {2051-3380}, abstract = {Malignant mesothelioma is a rare and aggressive pleural or peritoneal tumour almost always caused by exposure to asbestos fibres. Exposure to asbestos can cause malignant mesothelioma 30-40 years after exposure. A description of sources of exposure is important for prevention and possible financial compensation. Three women with cases of histologically confirmed malignant mesothelioma diagnosed from non-occupational asbestos exposure are described. Patients were contacted for an interview to assess their exposure history to asbestos. All three cases had mixed exposure histories related to secondary, environmental contamination, and domestic exposure. This case series highlight how ubiquitous asbestos is in the environment and how diverse the exposures may be. It is anticipated that a significant number of cases of non-occupational mesothelioma will be seen in many countries for several decades given the extent of asbestos containing materials.}, } @article {pmid30475941, year = {2019}, author = {Consonni, D and Mensi, C}, title = {Comment on the paper 'Boffetta et al. Validation of the diagnosis of mesothelioma and BAP1 protein expression in a cohort of asbestos textile workers from Northern Italy. Ann Oncol 2018; 29(2): 484-489'.}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {30}, number = {2}, pages = {340-341}, doi = {10.1093/annonc/mdy521}, pmid = {30475941}, issn = {1569-8041}, mesh = {*Asbestos ; Humans ; Italy ; *Lung Neoplasms ; *Mesothelioma ; Textiles ; Tumor Suppressor Proteins ; Ubiquitin Thiolesterase ; }, } @article {pmid30455474, year = {2018}, author = {Affar, EB and Carbone, M}, title = {BAP1 regulates different mechanisms of cell death.}, journal = {Cell death & disease}, volume = {9}, number = {12}, pages = {1151}, pmid = {30455474}, issn = {2041-4889}, support = {R01 CA198138/CA/NCI NIH HHS/United States ; 399244//CIHR/Canada ; }, mesh = {*Apoptosis ; Cell Death ; Humans ; *Neoplasms ; Tumor Suppressor Proteins ; Ubiquitin Thiolesterase ; }, } @article {pmid30451473, year = {2018}, author = {Krówczyńska, M and Wilk, E and Pabjanek, P and Olędzka, G}, title = {Pleural mesothelioma in Poland: Spatial analysis of malignant mesothelioma prevalence in the period 1999-2013.}, journal = {Geospatial health}, volume = {13}, number = {2}, pages = {}, doi = {10.4081/gh.2018.667}, pmid = {30451473}, issn = {1970-7096}, mesh = {Air Pollutants/analysis ; Asbestos/*analysis ; Female ; Humans ; Incidence ; Inhalation Exposure/analysis ; Lung Neoplasms/*chemically induced/*epidemiology ; Male ; Mesothelioma/*chemically induced/*epidemiology ; Mesothelioma, Malignant ; Pleural Neoplasms/*chemically induced/*epidemiology ; Poland/epidemiology ; Prevalence ; Spatial Analysis ; }, abstract = {Malignant mesothelioma (MM), a rare and very deadly tumour, can be due to asbestos exposure. To better understand the cause of incidence of MM, spatial autocorrelation analysis with reference to the quantity of asbestos-cement products in use and the localisation of former asbestos manufacturing plants was applied. Geostatistical analysis shows that strong spatial clustering of MM incidence (referring to the general population as well as females and males separately) during the period 1999-2013 in the administrative units of Poland (provinces and counties). Incidence hotspots were found to be concentrated primarily in southern Poland but also seen in the county of Szczecin, which stands out in local autocorrelation analysis in north-western Poland. High incidence rates were discovered, in particular with reference to counties around former plants manufacturing asbestos-containing products, mainly asbestos-cement manufacturers. The highest frequency of MM incidence rate was found in within a 55 km radius of plants in or near the towns Trzebinia, Ogrodzieniec and Szczucin in the South, where asbestos-cement products had been manufactured for close to 40 years. Areas with significantly high incidence rates were also discovered in the provinces of Śląskie, Małopolskie and Świętokrzyskie in southern Poland.}, } @article {pmid30451463, year = {2018}, author = {Krówczyńska, M and Wilk, E}, title = {Spatial analysis of asbestos exposure and occupational health care in Poland during the period 2004-2013.}, journal = {Geospatial health}, volume = {13}, number = {2}, pages = {}, doi = {10.4081/gh.2018.689}, pmid = {30451463}, issn = {1970-7096}, mesh = {Air Pollutants, Occupational/adverse effects/*analysis ; Asbestos/*adverse effects/analysis ; Asbestosis/epidemiology ; Humans ; Inhalation Exposure/adverse effects/*analysis ; Lung Neoplasms/chemically induced/epidemiology ; Manufacturing Industry ; Mesothelioma/chemically induced/epidemiology ; Mineral Fibers ; Occupational Exposure/adverse effects/*analysis ; Occupational Health/*statistics & numerical data ; Poland/epidemiology ; Smoking/epidemiology ; *Spatial Analysis ; Time Factors ; }, abstract = {Asbestos is carcinogenic to humans and exposure to this substance can cause a wide range of diseases. In Poland 1997, a statutory ban was introduced on the production, use and marketing of products containing asbestos. The National Programme for Asbestos Abatement for 2009-2032 includes scheduled activities considering asbestos exposure assessment and health protection. As there are several data sources for asbestos exposure in Poland, which are not linked, the aim of this study was to gather and order them developing a PostgreSQL database, an open-source, objectrelational system. The data gathered combines the following information: the quantity of asbestos-cement products in use, details of asbestos manufacturing plants, the results of the measurements of asbestos fibre concentrations in the air and cases of asbestos-related diseases. The relational database was then used to develop a spatial analysis of asbestos monitoring and exposure in Poland to demonstrate the current state of realisation of the National Asbestos Abatement Programme in the country for 2009-2032 with the use of geoinformation techniques. The use of a database on health aspects of occupational and environmental asbestos exposure was also proposed in Asbestos, Asbestosis, and Cancer: Helsinki Criteria update 2014.}, } @article {pmid30450291, year = {2018}, author = {Broeckx, G and Pauwels, P}, title = {Malignant peritoneal mesothelioma: a review.}, journal = {Translational lung cancer research}, volume = {7}, number = {5}, pages = {537-542}, pmid = {30450291}, issn = {2218-6751}, abstract = {Malignant peritoneal mesothelioma (MPM) is a very rare malignancy of the peritoneum and has a poor prognosis. Of all mesotheliomas, pleural mesothelioma is more common than MPM. In comparison to pleural mesothelioma, the link with asbestos exposure is weaker (33-50% vs. >80%), but it is still the best-defined risk factor. MPM spreads predominantly expansive rather than infiltrative and symptoms are related to tumor spread within the abdominal cavity. Often, MPM is encountered incidentally by diagnostic imaging or by surgery. Computed tomography scan is widely accepted as a first line modality in diagnostic imaging. In diagnostic histopathology, MPM presents some challenges. Firstly, adequate clinical information is of utmost importance to consider the possibility of the diagnosis of MPM. Furthermore, a few morphological subtypes and variants exist. The most sensitive immunohistochemical markers are calretinin (100%), WT1 (94%) and CK5/6 (89%). The malignant character of immunohistochemically demonstrated mesothelial cells is not always obvious. This paradigm somewhat changed with the advent of immunohistochemical demonstration of BAP1 (BRCA-1 associated protein 1). Loss of BAP1 expression supports a diagnosis of malignancy. The gold standard in treatment remains cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC). Targetable molecular pathways in MPM are being identified. An exciting finding was the demonstration of ALK rearrangements in a small subset of patients with MPM and it is hoped for that at least this small subgroup of patients could benefit from treatment with ALK inhibitors. First-generation tyrosine kinase inhibitors against epidermal growth factor receptor (EGFR) did not show any significant activity in MPM. In contrast, nintedanib, an angiokinase inhibitor, improved progression-free survival and bevacizumab, a humanized anti-VEGF antibody increased overall survival in patients with MPM, when administered in combination with cisplatin and pemetrexed. Ongoing immunotherapy trials will offer a possible new treatment.}, } @article {pmid30450290, year = {2018}, author = {Brusselmans, L and Arnouts, L and Millevert, C and Vandersnickt, J and van Meerbeeck, JP and Lamote, K}, title = {Breath analysis as a diagnostic and screening tool for malignant pleural mesothelioma: a systematic review.}, journal = {Translational lung cancer research}, volume = {7}, number = {5}, pages = {520-536}, pmid = {30450290}, issn = {2218-6751}, abstract = {Malignant pleural mesothelioma (MPM) is a tumour related to a historical exposure to asbestos fibres. Currently, the definite diagnosis is made only by the histological examination of a biopsy obtained through an invasive thoracoscopy. However, diagnosis is made too late for curative treatment because of non-specific symptoms mainly appearing at advanced stage disease. Hence, due to its biologic aggressiveness and the late diagnosis, survival rate is low and the patients' outcome poor. In addition, radiological imaging, like computed tomographic scans, and blood biomarkers are found not to be sensitive enough to be used as an early diagnostic tool. Detection in an early stage is assumed to improve the patients' outcome but is hampered due to non-specific and late symptomology. Hence, there is a need for a new screening and diagnostic test which could improve the patients' outcome. Despite extensive research has focused on blood biomarkers, not a single has been shown clinically useful, and therefore research recently shifted to "breathomics" techniques to recognize specific volatile organic compounds (VOCs) in the breath of the patient as potential non-invasive biomarkers for disease. In this review, we summarize the acquired knowledge about using breath analysis for diagnosing and monitoring MPM and asbestos-related disorders (ARD). Gas chromatography-mass spectrometry (GC-MS), the gold standard of breath analysis, appears to be the method with the highest accuracy (97%) to differentiate MPM patients from at risk asbestos-exposed subjects. There have already been found some interesting biomarkers that are significantly elevated in asbestosis (NO, 8-isoprostane, leukotriene B4, α-Pinene…) and MPM (cyclohexane) patients. Regrettably, the different techniques and the plethora of studies suffer some limitations. Most studies are pilot studies with the inclusion of a limited number of patients. Nevertheless, given the promising results and easy sampling methods, we can conclude that breath analysis may become a useful tool in the future to screen for MPM, but further research is warranted.}, } @article {pmid30450289, year = {2018}, author = {Nuyts, V and Nawrot, T and Nemery, B and Nackaerts, K}, title = {Hotspots of malignant pleural mesothelioma in Western Europe.}, journal = {Translational lung cancer research}, volume = {7}, number = {5}, pages = {516-519}, pmid = {30450289}, issn = {2218-6751}, abstract = {Malignant pleural mesothelioma, a highly invasive tumour, has been epidemiologically linked to an occupational or environmental exposure to asbestos. Although asbestos has been widely used in diverse industrial applications and in construction, some industrial sectors have been affected much more than others. The objective of this review was to describe the existence of clusters of malignant pleural mesothelioma in Western European countries, based on epidemiological studies published between 2000 and 2015. MEDLINE (PubMed) and Embase were searched for relevant studies on spatial clustering of mesothelioma in Western European countries. Eventually, 16 different studies published between 2000 and 2015 were selected for a comprehensive analysis. Relevant studies on spatial clustering of mesothelioma were found for Belgium, the Netherlands, the United Kingdom, Germany, France, Spain, Italy and Denmark. Clustering of pleural mesothelioma was found mainly around shipyards (16 studies) and asbestos cement industries (10 studies). Although malignant pleural mesothelioma may be found throughout Western Europe, the present study indicates specific areas with higher past and also probable future incidence.}, } @article {pmid30446780, year = {2018}, author = {Feder, IS and Jülich, M and Tannapfel, A and Tischoff, I}, title = {[The German Mesothelioma Register : Current pathological diagnostics and services].}, journal = {Der Pathologe}, volume = {39}, number = {Suppl 2}, pages = {241-246}, pmid = {30446780}, issn = {1432-1963}, mesh = {*Asbestos ; Germany ; Humans ; Lung ; *Lung Neoplasms ; *Mesothelioma ; *Occupational Exposure ; Tumor Suppressor Proteins ; Ubiquitin Thiolesterase ; }, abstract = {BACKGROUND: In Germany, asbestos-related diseases (asbestosis, lung cancer, mesothelioma) are recognised and compensated occupational diseases. The histologic diagnosis of mesothelioma is sometimes a challenge; additional immunohistochemical and molecular methods are needed. With lung dust analysis, the current asbestos fibre burden of the lung is measured (biomonitoring). Identification of grade I asbestosis (minimal asbestosis) requires directed histological examinations with up to 400-fold magnification, additional iron staining and possibly in connection with a lung dust analysis.

OBJECTIVES: Demonstration of current pathologic diagnostics in association with mesothelioma and lung dust analysis.

MATERIALS AND METHODS: Analysis of routine data from the German Mesothelioma Register.

RESULTS: Contrary to reactive mesothelial hyperplasia, malignant mesotheliomas have a nuclear BAP1 loss-of-expression in up to 66% of cases. For differential diagnosis between reactive versus malignant, a p16-FISH test may be helpful. BAP1 loss-of-expression and p16-deletion are independent markers. Evaluation of the dataset of the German Mesothelioma Register of patients with repeated tissue sampling proves the detection of asbestos fibres at the same level even after 40 years. The asbestos fibre burden in the human lung remains stable over this long period of time. In the electron microscopic analysis, white asbestos was predominantly found.

CONCLUSIONS: The well-known and industrially appreciated characteristics of asbestos fibres (in ancient ἄσβεστος asbestos "imperishable") as biopersistent have also been experimentally confirmed in human lungs.}, } @article {pmid30426024, year = {2018}, author = {Kumagai-Takei, N and Nishimura, Y and Matsuzaki, H and Lee, S and Yoshitome, K and Otsuki, T}, title = {Decrease in Intracellular Perforin Levels and IFN-γ Production in Human CD8[+] T Cell Line following Long-Term Exposure to Asbestos Fibers.}, journal = {Journal of immunology research}, volume = {2018}, number = {}, pages = {4391731}, pmid = {30426024}, issn = {2314-7156}, mesh = {Asbestos/adverse effects ; Asbestos, Serpentine/adverse effects ; CD8-Positive T-Lymphocytes/*immunology ; Cell Degranulation ; Cell Line ; Environmental Exposure/adverse effects ; Granzymes/metabolism ; Humans ; Interferon-gamma/*metabolism ; Lung Neoplasms/immunology/*metabolism ; Lymphocyte Activation ; Mesothelioma/immunology/*metabolism ; Mesothelioma, Malignant ; Perforin/*metabolism ; }, abstract = {Although the tumorigenicity of asbestos, which is thought to cause mesothelioma, has been clarified, its effect on antitumor immunity requires further investigation. We previously reported a decrease in the percentage of perforin[+] cells of stimulated CD8[+] lymphocytes derived from patients with malignant mesothelioma. Therefore, we examined the effects of long-term exposure to asbestos on CD8[+] T cell functions by comparing long-term cultures of the human CD8[+] T cell line EBT-8 with and without exposure to chrysotile (CH) asbestos as an in vitro model. Exposure to CH asbestos at 5 μg/ml or 30 μg/ml did not result in a decrease in intracellular granzyme B in EBT-8 cells. In contrast, the percentage of perforin[+] cells decreased at both doses of CH exposure. CH exposure at 30 μg/ml did not suppress degranulation following stimulation with antibodies to CD3. Secreted production of IFN-γ stimulated via CD3 decreased by CH exposure at 30 μg/ml, although the percentage of IFN-γ [+] cells induced by PMA/ionomycin did not decrease. These results indicate that long-term exposure to asbestos can potentially suppress perforin levels and the production of IFN-γ in human CD8[+] T cells.}, } @article {pmid30417819, year = {2018}, author = {Røe, OD}, title = {[Asbestos and mesothelioma in Denmark 2017: status of a man-made cancer epidemic].}, journal = {Ugeskrift for laeger}, volume = {180}, number = {46}, pages = {}, pmid = {30417819}, issn = {1603-6824}, mesh = {*Asbestos/adverse effects ; Denmark/epidemiology ; Humans ; *Lung Neoplasms ; *Mesothelioma/epidemiology ; *Pleural Neoplasms/epidemiology ; Risk Factors ; }, abstract = {Asbestos-induced cancer is an increasing problem in Denmark, and 32 years after the closure of the Danish Eternit Factory in Aalborg there are > 140 new mesothelioma cases diagnosed yearly, numbers rapidly increasing. Asbestos-induced lung cancer may be six times this number. The non-occupational exposure and even neighborhood exposure as a risk factor suggests, that compensation for mesothelioma should be universal. At the Aalborg University Hospital a multidisciplinary research team has been formed to do epidemiological, translational and clinical studies through national and international collaborations. Transformative research on asbestos cancer should be stimulated.}, } @article {pmid30410726, year = {2018}, author = {Berzenji, L and Van Schil, P}, title = {Multimodality treatment of malignant pleural mesothelioma.}, journal = {F1000Research}, volume = {7}, number = {}, pages = {}, pmid = {30410726}, issn = {2046-1402}, mesh = {Animals ; Combined Modality Therapy/*methods/standards/trends ; Humans ; Lung Neoplasms/mortality/*therapy ; Mesothelioma/mortality/*therapy ; Mesothelioma, Malignant ; Pleura/pathology ; Rare Diseases/therapy ; Treatment Outcome ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare disease of the pleura and is largely related to asbestos exposure. Despite recent advancements in technologies and a greater understanding of the disease, the prognosis of MPM remains poor; the median overall survival rate is about 6 to 9 months in untreated patients. The main therapeutic strategies for MPM are surgery, chemotherapy, and radiation therapy (RT). The two main surgical approaches for MPM are extrapleural pneumonectomy (EPP), in which the lung is removed en bloc, and pleurectomy/decortication, in which the lung stays in situ. Chemotherapy usually consists of a platinum-based chemotherapy, such as cisplatin, often combined with a folate antimetabolite, such as pemetrexed. More recently, immunotherapy has emerged as a possible therapeutic strategy for MPM. Evidence suggests that single-modality treatments are not an effective therapeutic approach for MPM. Therefore, researchers have started to explore different multimodality treatment approaches, in which often combinations of surgery, chemotherapy, immunotherapy, and RT are investigated. There is still no definitive answer to the question of which multimodality treatment combinations are most effective in improving the poor prognosis of MPM. Research into the effects of trimodality treatment approaches have found that radical approaches such as EPP and hemithoracic RT post-EPP are less effective than was previously assumed. In general, there are still a great number of unanswered questions and unknown factors regarding the ideal treatment approach for MPM. Hopefully, more research into multimodality therapy will provide insight into which combination of treatment modalities is most effective.}, } @article {pmid30408567, year = {2019}, author = {Guarrera, S and Viberti, C and Cugliari, G and Allione, A and Casalone, E and Betti, M and Ferrante, D and Aspesi, A and Casadio, C and Grosso, F and Libener, R and Piccolini, E and Mirabelli, D and Dianzani, I and Magnani, C and Matullo, G}, title = {Peripheral Blood DNA Methylation as Potential Biomarker of Malignant Pleural Mesothelioma in Asbestos-Exposed Subjects.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {14}, number = {3}, pages = {527-539}, doi = {10.1016/j.jtho.2018.10.163}, pmid = {30408567}, issn = {1556-1380}, mesh = {Aged ; Asbestos/*adverse effects ; Biomarkers, Tumor/blood/*genetics ; Carcinogens/toxicity ; Case-Control Studies ; DNA/*blood/chemistry/genetics ; *DNA Methylation ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/blood/*diagnosis/etiology/pathology ; Male ; Mesothelioma/blood/*diagnosis/etiology/pathology ; Mesothelioma, Malignant ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/blood/*diagnosis/etiology/pathology ; Prognosis ; ROC Curve ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is an aggressive tumor strongly associated with asbestos exposure. Patients are usually diagnosed when current treatments have limited benefits, highlighting the need for noninvasive early diagnostic tests to monitor asbestos-exposed people.

METHODS: We used a genome-wide methylation array to identify, in asbestos-exposed subjects, novel blood DNA methylation markers of MPM in 163 MPM cases and 137 cancer-free controls (82 MPM cases and 68 controls, training set; replication in 81 MPM cases and 69 controls, test set) sampled from the same areas.

RESULTS: Evidence of differential methylation between MPM cases and controls was found (more than 800 cytosine-guanine dinucleotide sites, false discovery rate p value (pfdr) < 0.05), mainly in immune system-related genes. Considering the top differentially methylated signals, seven single- cytosine-guanine dinucleotides and five genomic regions of coordinated methylation replicated with similar effect size in the test set (pfdr < 0.05). The top hypomethylated single-CpG (cases versus controls effect size less than -0.15, pfdr < 0.05 in both the training and test sets) was detected in FOXK1 (Forkhead-box K1) gene, an interactor of BAP1 which was found mutated in MPM tissue and as germline mutation in familial MPM. In the test set, comparison of receiver operating characteristic curves and the area under the curve (AUC) of two models, including or excluding methylation, showed a significant increase in case/control discrimination when considering DNA methylation together with asbestos exposure (AUC = 0.81 versus AUC = 0.89, DeLong's test p = 0.0013).

CONCLUSIONS: We identified signatures of differential methylation in DNA from whole blood between asbestos exposed MPM cases and controls. Our results provide the rationale to further investigate, in prospective studies, the potential use of blood DNA methylation profiles for the identification of early changes related to the MPM carcinogenic process.}, } @article {pmid30401981, year = {2019}, author = {Matsushita, A and Sato, T and Mukai, S and Fujishita, T and Mishiro-Sato, E and Okuda, M and Aoki, M and Hasegawa, Y and Sekido, Y}, title = {TAZ activation by Hippo pathway dysregulation induces cytokine gene expression and promotes mesothelial cell transformation.}, journal = {Oncogene}, volume = {38}, number = {11}, pages = {1966-1978}, pmid = {30401981}, issn = {1476-5594}, support = {25090053//Japan Society for the Promotion of Science (JSPS)/International ; 16H04706//Japan Society for the Promotion of Science (JSPS)/International ; 17K19628//Japan Society for the Promotion of Science (JSPS)/International ; }, mesh = {Animals ; Cell Line, Tumor ; Cell Transformation, Neoplastic/*genetics ; Cytokines/*genetics/metabolism ; Epithelium/metabolism/pathology ; Female ; Gene Expression Regulation, Neoplastic ; Hippo Signaling Pathway ; Humans ; Intracellular Signaling Peptides and Proteins/*genetics/metabolism ; Lung Neoplasms/*genetics/metabolism/pathology ; Mesothelioma/*genetics/metabolism/pathology ; Mesothelioma, Malignant ; Mice ; Mice, Nude ; Protein Serine-Threonine Kinases/*genetics/metabolism ; Signal Transduction/genetics ; Trans-Activators ; Transcription Factors/*genetics/metabolism ; Transcriptional Activation ; Transcriptional Coactivator with PDZ-Binding Motif Proteins ; }, abstract = {Malignant mesothelioma (MM) constitutes a very aggressive tumor that is caused by asbestos exposure after long latency. The NF2 tumor suppressor gene is mutated in 40-50% of MM; moreover, one of its downstream signaling cascades, the Hippo signaling pathway, is also frequently inactivated in MM cells. Although the YAP transcriptional coactivator, which is regulated by the Hippo pathway, can function as a pro-oncogenic protein, the role of TAZ, a paralog of YAP, in MM cells has not yet been clarified. Here, we show that TAZ is expressed and underphosphorylated (activated) in the majority of MM cells compared to immortalized mesothelial cells. ShRNA-mediated TAZ knockdown highly suppressed cell proliferation, anchorage-independent growth, cell motility, and invasion in MM cells harboring activated TAZ. Conversely, transduction of an activated form of TAZ in immortalized mesothelial cells enhanced these in vitro phenotypes and conferred tumorigenicity in vivo. Microarray analysis determined that activated TAZ most significantly enhanced the transcription of genes related to "cytokine-cytokine receptor interaction." Among selected cytokines, we found that IL-1 signaling activation plays a major role in proliferation in TAZ-activated MM cells. Both IL1B knockdown and an IL-1 receptor antagonist significantly suppressed malignant phenotypes of immortalized mesothelial cells and MM cells with activated TAZ. Overall, these results indicate an oncogenic role for TAZ in MMs via transcriptional induction of distinct pro-oncogenic genes including cytokines. Among these, IL-1 signaling appears as one of the most important cascades, thus potentially serving as a target pathway in MM cells harboring Hippo pathway inactivation.}, } @article {pmid30376426, year = {2018}, author = {Pastorino, S and Yoshikawa, Y and Pass, HI and Emi, M and Nasu, M and Pagano, I and Takinishi, Y and Yamamoto, R and Minaai, M and Hashimoto-Tamaoki, T and Ohmuraya, M and Goto, K and Goparaju, C and Sarin, KY and Tanji, M and Bononi, A and Napolitano, A and Gaudino, G and Hesdorffer, M and Yang, H and Carbone, M}, title = {A Subset of Mesotheliomas With Improved Survival Occurring in Carriers of BAP1 and Other Germline Mutations.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {36}, number = {35}, pages = {JCO2018790352}, pmid = {30376426}, issn = {1527-7755}, support = {R01 CA198138/CA/NCI NIH HHS/United States ; U01 CA111295/CA/NCI NIH HHS/United States ; }, abstract = {PURPOSE: We hypothesized that four criteria could help identify malignant mesotheliomas (MMs) most likely linked to germline mutations of BAP1 or of other genes: family history of MM, BAP1-associated cancers, or multiple malignancies; or age younger than 50 years.

PATIENTS AND METHODS: Over the course of 7 years, 79 patients with MM met the four criteria; 22 of the 79 (28%) reported possible asbestos exposure. They were screened for germline BAP1 mutations by Sanger sequencing and by targeted next-generation sequencing (tNGS) for germline mutations in 55 additional cancer-linked genes. Deleterious mutations detected by tNGS were validated by Sanger sequencing.

RESULTS: Of the 79 patients, 43 (16 probands and 27 relatives) had deleterious germline BAP1 mutations. The median age at diagnosis was 54 years and median survival was 5 years. Among the remaining 36 patients with no BAP1 mutation, median age at diagnosis was 45 years, median survival was 9 years, and 12 had deleterious mutations of additional genes linked to cancer. When compared with patients with MMs in the SEER cohort, median age at diagnosis (72 years), median survival for all MM stages (8 months), and stage I (11 months) were significantly different from the 79 patients with MM in the current study (P < .0001).

CONCLUSION: We provide criteria that help identify a subset of patients with MM who had significantly improved survival. Most of these patients were not aware of asbestos exposure and carried either pathogenic germline mutations of BAP1 or of additional genes linked to cancer, some of which may have targeted-therapy options. These patients and their relatives are susceptible to development of additional cancers; therefore, genetic counseling and cancer screening should be considered.}, } @article {pmid30375909, year = {2019}, author = {Laaksonen, S and Ilonen, I and Kuosma, E and Sutinen, E and Wolff, H and Vehmas, T and Husgafvel-Pursiainen, K and Salo, JA and Koli, K and Räsänen, J and Myllärniemi, M}, title = {Malignant pleural mesothelioma in Finland: regional and gender variation.}, journal = {Acta oncologica (Stockholm, Sweden)}, volume = {58}, number = {1}, pages = {38-44}, doi = {10.1080/0284186X.2018.1532599}, pmid = {30375909}, issn = {1651-226X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Finland/epidemiology ; Humans ; Incidence ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/*epidemiology ; Registries ; Sex Distribution ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare occupational cancer with a poor prognosis. Even with a multimodality treatment approach, the treatment outcomes remain unsatisfactory. The use of asbestos has been banned in most developed countries, but MPM continues to be a significant occupational disease also in these countries. Aim of this study is to identify modern epidemiology and assess equality in care.

METHODS: Our study cohort consists of 1010 patients diagnosed with MPM in Finland during 2000-2012. The data were collected from the Finnish Cancer Registry, the National Workers' Compensation Center Registry and the National Registry of Causes of Death, Statistics Finland.

RESULTS: Women were diagnosed a mean of 4.5 years later than males (p = .001), but survival did not differ (overall median survival 9.7 months). A workers' compensation claim was more common in males (OR 11.0 [95% CI 7.5-16.2]) and in regions with a major asbestos industry (OR 1.7 [95% CI 1.3-2.2]). One-year and three-year survivals did not differ regionally. Patients without chemotherapy treatment had an inferior survival (RR 1.8 [95% CI 1.5-2.0]). The initial survival benefit gained with pemetrexed was diluted at 51 months.

CONCLUSIONS: MPM is a disease with a poor prognosis, although chemotherapy appears to improve survival time. Significant gender and regional variation exists among patients, with notable differences in diagnostic and treatment practices. Long-term outcomes with pemetrexed remain indeterminate.

IMPACT: Emphasize centralized consult services for the diagnosis, treatment and support that patients receive for MPM, facilitating equal outcomes and compensation.}, } @article {pmid30370748, year = {2018}, author = {Algranti, E and Giannasi, F and Sousa Santana, V}, title = {[The fight for the asbestos ban in Brazil and the 2nd International seminar "Brazil without asbestos"].}, journal = {Epidemiologia e prevenzione}, volume = {42}, number = {5-6}, pages = {388-390}, doi = {10.19191/EP18.5-6.P388.115}, pmid = {30370748}, issn = {1120-9763}, mesh = {*Asbestos/toxicity ; Asbestosis/*prevention & control ; Brazil ; Congresses as Topic ; Construction Materials/standards/statistics & numerical data ; Environmental Policy/*legislation & jurisprudence ; *Environmental Pollutants/toxicity ; Environmental Pollution/legislation & jurisprudence/*prevention & control ; Flame Retardants/toxicity ; Humans ; Mesothelioma/etiology/prevention & control ; Occupational Health/legislation & jurisprudence ; Pleural Neoplasms/etiology/prevention & control ; }, } @article {pmid30370160, year = {2018}, author = {Plato, N and Martinsen, JI and Kjaerheim, K and Kyyronen, P and Sparen, P and Weiderpass, E}, title = {Mesothelioma in Sweden: Dose-Response Analysis for Exposure to 29 Potential Occupational Carcinogenic Agents.}, journal = {Safety and health at work}, volume = {9}, number = {3}, pages = {290-295}, pmid = {30370160}, issn = {2093-7911}, abstract = {BACKGROUND: There is little information on the dose-response relationship between exposure to occupational carcinogenic agents and mesothelioma. This study aimed to investigate this association as well as the existence of agents other than asbestos that might cause mesothelioma.

METHODS: The Swedish component of the Nordic Occupational Cancer (NOCCA) study consists of 6.78 million individuals with detailed information on occupation. Mesothelioma diagnoses recorded in 1961-2009 were identified through linkage to the Swedish Cancer Registry. We determined cumulative exposure, time of first exposure, and maximum exposure intensity by linking data on occupation to the Swedish NOCCA job-exposure matrix, which includes 29 carcinogenic agents and corresponding exposure for 283 occupations. To assess the risk of mesothelioma, we used conditional logistic regression models to estimate hazard ratios and 95% confidence intervals.

RESULTS: 2,757 mesothelioma cases were identified in males, including 1,416 who were exposed to asbestos. Univariate analyses showed not only a significant excess risk for maximum exposure intensity, with a hazard ratio of 4.81 at exposure levels 1.25-2.0 fb/ml but also a clear dose-response effect for cumulative exposure with a 30-, 40-, and 50-year latency time. No convincing excess risk was revealed for any of the other carcinogenic agents included in the Swedish NOCCA job-exposure matrix.

CONCLUSION: When considering asbestos exposure, past exposure, even for short periods, might be enough to cause mesothelioma of the pleura later in life.}, } @article {pmid30366103, year = {2019}, author = {Harris, EJA and Kao, S and McCaughan, B and Nakano, T and Kondo, N and Hyland, R and Nowak, AK and de Klerk, NH and Brims, FJH}, title = {Prediction modelling using routine clinical parameters to stratify survival in Malignant Pleural Mesothelioma patients undergoing cytoreductive surgery.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {14}, number = {2}, pages = {288-293}, doi = {10.1016/j.jtho.2018.10.005}, pmid = {30366103}, issn = {1556-1380}, mesh = {Aged ; Anemia/blood ; Chest Pain/etiology ; Cytoreduction Surgical Procedures ; Dyspnea/etiology ; Female ; Health Status Indicators ; Hemoglobins/metabolism ; Humans ; Male ; Mesothelioma/blood/complications/pathology/*surgery ; Middle Aged ; *Models, Statistical ; Pleural Neoplasms/blood/complications/pathology/*surgery ; Risk Assessment/methods ; Risk Factors ; Serum Albumin/metabolism ; Survival Rate ; Weight Loss ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is an uncommon cancer with a poor prognosis and heterogeneous survival. Surgery for MPM is offered in some specialist centers to highly selected patients. A previously described classification and regression tree (CART) model stratified survival in unselected MPM patients using routinely collected clinical data. This study aimed to examine the performance of this CART model on a highly selected surgical population.

METHODS: Data were collected from subjects undergoing cytoreductive surgery for MPM from specialist centers in Hyõgo, Japan, and Sydney, Australia, between 1991 and 2016. The CART model was applied using the combination of clinical variables to stratify subjects into risk groups (1 through 4); survival characteristics were then compared.

RESULTS: Two hundred eighty-nine cases were included (205 from Australia, 84 from Japan). Overall median survival was 34.6 (interquartile range: 17.5-56.1) months; median age was 63.0 (interquartile range: 57.0-67.8) years, and 83.0% (n = 240) were male. There were no clinically meaningful differences between the two cohorts. Survival across the four risk groups was significantly different (p < 0.0001); the model stratified survival well with a Harrell's concordance statistic of 0.62 (95% confidence interval: 0.57-0.66) at 36 months. The group with the longest survival (median, 82.5 months) had: no weight loss, hemoglobin > 153 g/L and serum albumin > 43 g/L at time of referral to the surgical center.

CONCLUSIONS: Using routinely available clinical variables, the CART model was able to stratify surgical patients into risk groups with statistically different survival characteristics with fair to good performance. Presence of weight loss, anemia, and low albumin should confer caution when considering surgical therapy for MPM.}, } @article {pmid30362690, year = {2018}, author = {Trenti, E and Palermo, SM and D'Elia, C and Comploj, E and Pycha, A and Carella, R and Pycha, A}, title = {Malignant mesothelioma of tunica vaginalis testis: Report of a very rare case with review of the literature.}, journal = {Archivio italiano di urologia, andrologia : organo ufficiale [di] Societa italiana di ecografia urologica e nefrologica}, volume = {90}, number = {3}, pages = {212-214}, doi = {10.4081/aiua.2018.3.212}, pmid = {30362690}, issn = {1124-3562}, mesh = {Adult ; Follow-Up Studies ; Frozen Sections ; Humans ; Lung Neoplasms/*diagnosis/pathology/surgery ; Lymph Node Excision ; Male ; Mesothelioma/*diagnosis/pathology/surgery ; Mesothelioma, Malignant ; Prognosis ; Testicular Hydrocele/*surgery ; Testicular Neoplasms/*diagnosis/pathology/surgery ; Tomography, X-Ray Computed ; }, abstract = {INTRODUCTION: Mesothelioma of the tunica vaginalis testis is a extremely rare tumor and represents 0.3 to 0.5% of all malignant mesotheliomas. Exposure to asbestos often precedes illness. Because of its low incidence and nonspecific clinical presentation, it is mostly diagnosed accidentally during surgery for other reasons and the prognosis is usually poor. We present a case of a patient with a mesothelioma of tunica vaginalis testis, diagnosed secondarily during hydrocele surgery, with long-term survival after radical surgery.

MATERIALS AND METHODS: a 40 years old patient was admitted to our department for routine surgery of a left hydrocele. During the operation a frozen section analysis was requested because of the unusual nodular thickening of the tunica vaginalis: the examination revealed a diffuse malignant mesothelioma with epithelioid structure and tubular-papillary proliferation. Therefore a left hemi-scrotectomy with left inguinal lymph node dissection was performed.

RESULTS: The definitive histology confirmed the previous report of diffuse malignant mesothelioma with angio-invasion but normal testicle findings and negative lymph nodes. No metastases were found on the CT-scan. For the first 2 years a CT was repeated every 4 months, for other 3 years every 6 months and then yearly. Six years after surgery the patient is classified as no evidence of disease.

CONCLUSIONS: malignant mesothelioma of the tunica vaginalis testis is a rare entity, often initially thought to be a hydrocele or an epididymal cyst. An aggressive approach with hemiscrotectomy with or without inguinal and retroperitoneal lymphadenectomy can reduce the risk of recurrence.}, } @article {pmid30362153, year = {2019}, author = {Matboli, M and Shafei, AE and Ali, MA and Gaber, AI and Galal, A and Tarek, O and Marei, M and Khairy, E and El-Khazragy, N and Anber, N and Abdel-Rahman, O}, title = {Clinical significance of serum DRAM1 mRNA, ARSA mRNA, hsa-miR-2053 and lncRNA-RP1-86D1.3 axis expression in malignant pleural mesothelioma.}, journal = {Journal of cellular biochemistry}, volume = {120}, number = {3}, pages = {3203-3211}, doi = {10.1002/jcb.27586}, pmid = {30362153}, issn = {1097-4644}, mesh = {Cerebroside-Sulfatase/*blood ; Female ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Linear Models ; Lung Neoplasms/*blood ; Male ; Membrane Proteins/*blood ; Mesothelioma/*blood ; Mesothelioma, Malignant ; MicroRNAs/*blood ; Pleural Neoplasms/*blood ; RNA, Long Noncoding/*blood ; Real-Time Polymerase Chain Reaction ; }, abstract = {AIM AND BACKGROUND: Malignant pleural mesothelioma (MPM) is a lethal cancer mainly caused by chronic exposure of asbestos. In this pilot study, we aimed to assess the expression of serum RNA-based biomarker panel exploring their clinical utility as diagnostic and prognostic biomarkers for MPM.

METHODS: We have selected an MPM-specific RNA-based biomarker panel through bioinformatics analysis based on the integration of DNA damage regulated autophagy modulator 1 (DRAM1) and arylsulfatase A (ARSA) gene expression with their epigenetic regulators microRNA (miR-2053) and long noncoding RNA (lncRNA-RP1-86D1.3). Then, quantitative real-time polymerase chain reaction (qPCR) validation in sera of 60 MPM patients, 20 chronic asbestos exposure patients, and 20 healthy volunteers was done. Lastly, the prognostic power of the selected panel was assessed.

RESULTS: The expression of serum DRAM1 messenger RNA (mRNA), ARSA mRNA, hsa-miR-2053 and lncRNA-RP1-86D1.3 were positive in 78.3%, 90%, 85%, and 83.3% of MPM patients, respectively. The RNA-based biomarker panel was able to discriminate between MPM patients and controls with high accuracy and their combined sensitivity reached 100% for the diagnosis of MPM. Kaplan-Meier analysis showed that hsa-miR-2053 is an independent prognostic factor of MPM.

CONCLUSION: Our preliminary data revealed that the chosen RNAs play an important role in driving MPM development and progression.}, } @article {pmid30357666, year = {2018}, author = {Pascotto, E and Gianoncelli, A and Calligaro, C and Marcuzzo, T and Melato, M and Rizzardi, C and Pascolo, L}, title = {Ferruginous bodies resolved by synchrotron XRF in a dog with peritoneal malignant mesothelioma.}, journal = {Environmental science and pollution research international}, volume = {25}, number = {35}, pages = {35707-35714}, pmid = {30357666}, issn = {1614-7499}, mesh = {Animals ; Asbestos/toxicity ; Dogs ; Environmental Exposure/*adverse effects ; Immunohistochemistry ; Iron/analysis ; Lung/pathology ; Lung Neoplasms/diagnostic imaging/*pathology ; Male ; Mesothelioma/diagnostic imaging/*pathology ; Mesothelioma, Malignant ; Peritoneal Neoplasms/diagnostic imaging/*pathology ; Silicon/analysis ; Spectrometry, X-Ray Emission ; Synchrotrons ; }, abstract = {Mesothelioma is a malignant tumor mainly correlated to occupational asbestos exposure. Rare reports describe its occurrence also in animals, mainly linked to asbestos in the environment. Asbestos exposure is demonstrated by the appearance of characteristic histological hallmarks: asbestos containing ferruginous bodies that are iron-based structures forming around fibers and also other dust particles. Here we present a clinical case of a suspect of mesothelioma in the peritoneum of a dog with parallel histological observation of ferruginous bodies. To possibly correlate the dog tumor to environmental exposure, we performed X-ray fluorescence (XRF) analyses at two different synchrotrons to resolve the ferruginous bodies' composition. While the histological examination diagnoses a tubulo-papillary mesothelioma, the XRF analyses show that ferruginous bodies contain Si particles, resembling formations of exogenous origin; however, the morphology is unlikely that of asbestos fibers. We speculate that the peritoneal mesothelioma of this dog could be related to environmental exposure to non-asbestos material.}, } @article {pmid30357324, year = {2019}, author = {Dragani, TA and Colombo, F and Pavlisko, EN and Roggli, VL}, title = {Response to comments on 'Malignant mesothelioma diagnosed at a younger age is associated with heavier asbestos exposure' by Farioli et al. and Oddone et al.}, journal = {Carcinogenesis}, volume = {40}, number = {3}, pages = {490-491}, doi = {10.1093/carcin/bgy145}, pmid = {30357324}, issn = {1460-2180}, mesh = {*Asbestos ; Humans ; *Lung Neoplasms ; *Mesothelioma ; }, } @article {pmid30349836, year = {2018}, author = {Ibrahim, AM and Al-Akchar, M and Obaidi, Z and Al-Johany, H}, title = {Malignant Peritoneal Mesothelioma: A Rare Cause of Ascites.}, journal = {Journal of investigative medicine high impact case reports}, volume = {6}, number = {}, pages = {2324709618807506}, pmid = {30349836}, issn = {2324-7096}, abstract = {Malignant peritoneal mesothelioma (MPM) is a rare diagnosis that presents with difficulties in diagnosis and management. This article reports a case of an 88-year-old male who presented with a 2-week history of abdominal distention and bloating. He worked at an insulation production factory between the ages of 23 and 25 years with presumed asbestos exposure. On the computed tomography scan of the abdomen/pelvis, the patient was found to have diffuse omental, peritoneal, and mesenteric nodularity with moderate to large ascites. Omental biopsy revealed MPM. The overall prognosis of MPM remains poor, with a median survival time of 12 months at the time of diagnosis. Treatment modalities offered in the United States include chemotherapy alone, cytoreductive surgery alone, or cytoreductive surgery/chemotherapy combination.}, } @article {pmid30349716, year = {2018}, author = {Grosso, F and Roveta, A and Gallizzi, G and Belletti, M}, title = {Management of recurrent pleural mesothelioma: Successful rechallenge with nintedanib in combination with chemotherapy.}, journal = {Clinical case reports}, volume = {6}, number = {10}, pages = {2000-2004}, pmid = {30349716}, issn = {2050-0904}, abstract = {Malignant pleural mesothelioma (MPM) is a rare neoplasm, generally caused by asbestos exposure. This case details how a patient treated with nintedanib during the LUME-Meso study was rechallenged with nintedanib. The findings highlight the benefit of nintedanib rechallenge and the potential use of continuous anti-angiogenic therapy in MPM treatment.}, } @article {pmid30349644, year = {2018}, author = {Adhikary, G and Grun, D and Alexander, HR and Friedberg, JS and Xu, W and Keillor, JW and Kandasamy, S and Eckert, RL}, title = {Transglutaminase is a mesothelioma cancer stem cell survival protein that is required for tumor formation.}, journal = {Oncotarget}, volume = {9}, number = {77}, pages = {34495-34505}, pmid = {30349644}, issn = {1949-2553}, support = {R01 CA184027/CA/NCI NIH HHS/United States ; R01 CA211909/CA/NCI NIH HHS/United States ; T32 CA154274/CA/NCI NIH HHS/United States ; }, abstract = {Mesothelioma is a rare cancer of the mesothelial cell layer of the pleura, peritoneum, pericardium and tunica vaginalis. It is typically caused by asbestos, notoriously resistant to chemotherapy and generally considered incurable with a poor life expectancy. Transglutaminase 2 (TG2), a GTP binding regulatory protein, is an important cancer stem cell survival and therapy resistance factor. We show that TG2 is highly expressed in human mesothelioma tumors and in mesothelioma cancer stem cells (MCS cells). TG2 knockdown or TG2 inhibitor treatment reduces MCS cell spheroid formation, matrigel invasion, migration and tumor formation. Time to tumor first appearance is doubled in TG2 knockout cells as compared to wild-type. In addition, TG2 loss is associated with reduced expression of stemness, and epithelial mesenchymal transition markers, and enhanced apoptosis. These studies indicate that TG2 is an important MCS cell survival protein and suggest that TG2 may serve as a mesothelioma cancer stem cell therapy target.}, } @article {pmid30338612, year = {2018}, author = {Betti, M and Aspesi, A and Ferrante, D and Sculco, M and Righi, L and Mirabelli, D and Napoli, F and Rondón-Lagos, M and Casalone, E and Vignolo Lutati, F and Ogliara, P and Bironzo, P and Gironi, CL and Savoia, P and Maffè, A and Ungari, S and Grosso, F and Libener, R and Boldorini, R and Valiante, M and Pasini, B and Matullo, G and Scagliotti, G and Magnani, C and Dianzani, I}, title = {Sensitivity to asbestos is increased in patients with mesothelioma and pathogenic germline variants in BAP1 or other DNA repair genes.}, journal = {Genes, chromosomes & cancer}, volume = {57}, number = {11}, pages = {573-583}, doi = {10.1002/gcc.22670}, pmid = {30338612}, issn = {1098-2264}, support = {IG 17464//Associazione Italiana per la Ricerca sul Cancro/International ; 2015 IG 17464//Associazione Italiana per la Ricerca sul Cancro/International ; //Istituto Superiore di Sanità (Progetto Amianto)/International ; //Italian Institute for Genomic Medicine/International ; //Ministry of Health - Italy/International ; //Regione Piemonte/International ; GR-2011-02348356//Young Researcher/International ; 2011-02348356//Young Researcher/International ; //INAIL Bric program 2016-2018/International ; }, mesh = {Adult ; Asbestos/*adverse effects ; Cohort Studies ; DNA Repair/genetics ; Environmental Exposure/*analysis ; Female ; Genetic Predisposition to Disease/*genetics ; Germ-Line Mutation/*genetics ; Humans ; Italy ; Male ; Mesothelioma/epidemiology/*genetics ; Middle Aged ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {Pathogenic germline variants in the BAP1 tumor suppressor gene can cause a cancer syndrome called BAP1 tumor predisposition syndrome (BAP1-TPDS), which is characterized by predisposition to mesothelioma, melanoma, renal cell carcinoma, basal cell carcinoma, and other tumors. Other genes that may predispose to mesothelioma are CDKN2A and DNA repair genes. Asbestos exposure has often been reported in patients with malignant pleural mesothelioma (MPM) and germline variants in BAP1, but this exposure has never been quantified. We aimed to search for germline variants in BAP1 among 25 new Italian probands with suspected BAP1-TPDS, summarize the prevalence of these variants in 39 Italian patients with familial MPM and other tumors recruited over a 5-year period, and compare cumulative asbestos exposure in 14 patients with MPM and pathogenic germline variants in BAP1, CDKN2A, or DNA repair genes with that of 67 patients without germline variants in 94 cancer-predisposing genes. We report here a new pathogenic germline variant in BAP1: c.783 + 2 T > C. The prevalence of pathogenic germline variants in BAP1 was 7.7% among patients with familial MPM (3/39). Patients with pathogenic germline variants in BAP1, CDKN2A, or DNA repair genes showed lower cumulative asbestos exposure than patients without germline variants in 94 cancer-predisposing genes (P = .00002). This suggests an interaction between genetic risk factors and asbestos in the development of mesothelioma.}, } @article {pmid30321262, year = {2018}, author = {Brentisci, C and Gangemi, M and Migliore, E and Mirabelli, D and Stura, A}, title = {Comment on 'Validation of the diagnosis of mesothelioma and BAP1 protein expression in a cohort of asbestos textile workers from Northern Italy'.}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {29}, number = {12}, pages = {2395-2396}, doi = {10.1093/annonc/mdy463}, pmid = {30321262}, issn = {1569-8041}, mesh = {*Asbestos ; Humans ; Italy ; *Lung Neoplasms ; *Mesothelioma ; Textiles ; Tumor Suppressor Proteins ; Ubiquitin Thiolesterase ; }, } @article {pmid30319235, year = {2018}, author = {Jargin, SV}, title = {Asbestos and Mesothelioma: A Comment.}, journal = {Indian journal of occupational and environmental medicine}, volume = {22}, number = {2}, pages = {113-114}, pmid = {30319235}, issn = {0973-2284}, } @article {pmid30317900, year = {2018}, author = {Duke, KS and Thompson, EA and Ihrie, MD and Taylor-Just, AJ and Ash, EA and Shipkowski, KA and Hall, JR and Tokarz, DA and Cesta, MF and Hubbs, AF and Porter, DW and Sargent, LM and Bonner, JC}, title = {Role of p53 in the chronic pulmonary immune response to tangled or rod-like multi-walled carbon nanotubes.}, journal = {Nanotoxicology}, volume = {12}, number = {9}, pages = {975-991}, pmid = {30317900}, issn = {1743-5404}, support = {CC999999//Intramural CDC HHS/United States ; P30 ES025128/ES/NIEHS NIH HHS/United States ; R01 ES020897/ES/NIEHS NIH HHS/United States ; T32 ES007046/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Dose-Response Relationship, Drug ; Granuloma, Respiratory Tract/*chemically induced/genetics/immunology ; Inhalation Exposure ; Lung/*drug effects/immunology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Nanotubes, Carbon/*chemistry/*toxicity ; Surface Properties ; Tertiary Lymphoid Structures/*chemically induced/genetics/immunology ; Tumor Suppressor Protein p53/genetics/*physiology ; }, abstract = {The fiber-like shape of multi-walled carbon nanotubes (MWCNTs) is reminiscent of asbestos, suggesting they pose similar health hazards when inhaled, including pulmonary fibrosis and mesothelioma. Mice deficient in the tumor suppressor p53 are susceptible to carcinogenesis. However, the chronic pathologic effect of MWCNTs delivered to the lungs of p53 heterozygous (p53[+/-]) mice has not been investigated. We hypothesized that p53[+/-] mice would be susceptible to lung tumor development after exposure to either tangled (t-) or rod-like (r-) MWCNTs. Wild-type (p53[+/+]) or p53[+/-] mice were exposed to MWCNTs (1 mg/kg) via oropharyngeal aspiration weekly over four consecutive weeks and evaluated for cellular and pathologic outcomes 11-months post-initial exposure. No lung or pleural tumors were observed in p53[+/+] or p53[+/-] mice exposed to either t- or rMWCNTs. In comparison to tMWCNTs, the rMWCNTs induced the formation of larger granulomas, a greater number of lymphoid aggregates and greater epithelial cell hyperplasia in terminal bronchioles in both p53[+/-] and p53[+/+] mice. A constitutively larger area of CD45R[+]/CD3[+] lymphoid tissue was observed in p53[+/-] mice compared to p53[+/+] mice. Importantly, p53[+/-] mice had larger granulomas induced by rMWCNTs as compared to p53[+/+] mice. These findings indicate that a combination of p53 deficiency and physicochemical characteristics including nanotube geometry are factors in susceptibility to MWCNT-induced lymphoid infiltration and granuloma formation.}, } @article {pmid30316650, year = {2018}, author = {Fournel, L and Janet-Vendroux, A and Canny-Hamelin, E and Mansuet-Lupo, A and Guinet, C and Bobbio, A and Damotte, D and Alifano, M}, title = {[Malignant pleural mesothelioma: The role of surgery].}, journal = {Revue de pneumologie clinique}, volume = {74}, number = {5}, pages = {351-358}, doi = {10.1016/j.pneumo.2018.09.006}, pmid = {30316650}, issn = {1776-2561}, mesh = {Chemotherapy, Adjuvant ; Combined Modality Therapy ; Humans ; Lung Neoplasms/diagnosis/drug therapy/radiotherapy/*surgery ; Mesothelioma/diagnosis/drug therapy/radiotherapy/*surgery ; Mesothelioma, Malignant ; Pleural Neoplasms/diagnosis/drug therapy/radiotherapy/*surgery ; Pneumonectomy ; Radiotherapy, Adjuvant ; Thoracic Surgical Procedures/*methods ; Thoracoscopy ; Treatment Outcome ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is a rare and highly aggressive disease, whose incidence is increasing. Asbestos is the primary causal agent.

STATE OF KNOWLEDGE: Knowledge about MPM has evolved. Thoracoscopy is essential for diagnosis of MPM. It allows performing pleural biopsies, to study the extent of the disease and to relieve dyspnea. The pathological diagnosis is also better codified with immunohistochemistry and with analysis by expert of Mesopath group. Curative surgical treatments are pleurectomy decortication and extended pneumonectomy in combination with chemotherapy and/or radiotherapy. Those heavy treatments improve survival in highly selected patients. For the other patients, supportive measures will be considered to reduce pain and dyspnea.

PROSPECT: Radical surgical treatment is only offered in therapeutic trials or multimodal treatment. Its place is not formally established. New therapies associated to surgical treatment are being studied.

CONCLUSIONS: Surgical management of MPM has to be operated in specialized teams where the survival benefit and quality of life is discussed case by case.}, } @article {pmid30316012, year = {2019}, author = {Mansfield, AS and Peikert, T and Smadbeck, JB and Udell, JBM and Garcia-Rivera, E and Elsbernd, L and Erskine, CL and Van Keulen, VP and Kosari, F and Murphy, SJ and Ren, H and Serla, VV and Schaefer Klein, JL and Karagouga, G and Harris, FR and Sosa, C and Johnson, SH and Nevala, W and Markovic, SN and Bungum, AO and Edell, ES and Dong, H and Cheville, JC and Aubry, MC and Jen, J and Vasmatzis, G}, title = {Neoantigenic Potential of Complex Chromosomal Rearrangements in Mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {14}, number = {2}, pages = {276-287}, pmid = {30316012}, issn = {1556-1380}, support = {K12 CA090628/CA/NCI NIH HHS/United States ; }, mesh = {Antigens/*genetics ; *Chromothripsis ; Clonal Selection, Antigen-Mediated ; Computer Simulation ; DNA, Neoplasm/analysis ; Gene Dosage ; Gene Rearrangement ; Genomics ; HLA-A Antigens/genetics ; HLA-B Antigens/genetics ; Humans ; Lymphocytes, Tumor-Infiltrating ; Mesothelioma/*genetics/pathology ; Peptides/genetics/immunology ; Pleural Neoplasms/*genetics/pathology ; Receptors, Antigen, T-Cell/genetics ; Sequence Analysis, DNA/methods ; Sequence Analysis, RNA ; Survival Rate ; T-Lymphocytes/immunology ; Transcriptome/*genetics ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma is a disease primarily associated with exposure to the carcinogen asbestos. Whereas other carcinogen-related tumors are associated with a high tumor mutation burden, mesothelioma is not. We sought to resolve this discrepancy.

METHODS: We used mate-pair (n = 22), RNA (n = 28), and T cell receptor sequencing along with in silico predictions and immunologic assays to understand how structural variants of chromosomes affect the transcriptome.

RESULTS: We observed that inter- or intrachromosomal rearrangements were present in every specimen and were frequently in a pattern of chromoanagenesis such as chromoplexy or chromothripsis. Transcription of rearrangement-related junctions was predicted to result in many potential neoantigens, some of which were proven to bind patient-specific major histocompatibility complex molecules and to expand intratumoral T cell clones. T cells responsive to these predicted neoantigens were also present in a patient's circulating T cell repertoire. Analysis of genomic array data from the mesothelioma cohort in The Cancer Genome Atlas suggested that multiple chromothriptic-like events negatively impact survival.

CONCLUSIONS: Our findings represent the discovery of potential neoantigen expression driven by structural chromosomal rearrangements. These results may have implications for the development of novel immunotherapeutic strategies and the selection of patients to receive immunotherapies.}, } @article {pmid30312759, year = {2019}, author = {Toyokuni, S}, title = {Iron addiction with ferroptosis-resistance in asbestos-induced mesothelial carcinogenesis: Toward the era of mesothelioma prevention.}, journal = {Free radical biology & medicine}, volume = {133}, number = {}, pages = {206-215}, doi = {10.1016/j.freeradbiomed.2018.10.401}, pmid = {30312759}, issn = {1873-4596}, mesh = {Animals ; Asbestos/toxicity ; Carcinogenesis/chemically induced/*genetics/pathology ; Ferroptosis/*genetics ; Humans ; Iron/*metabolism ; Iron Overload/chemically induced/genetics/metabolism/pathology ; Lung Neoplasms/chemically induced/*metabolism/pathology ; Mesothelioma/chemically induced/*metabolism/pathology ; Mesothelioma, Malignant ; Nanotubes, Carbon/toxicity ; Rats ; Transferrin/metabolism ; }, abstract = {Cancer is the primary cause of human mortality in most countries. This tendency has increased as various medical therapeutics have advanced, which suggests that we cannot escape carcinogenesis, although the final outcome may be modified by exposomes and statistics. Cancer is classified by its cellular differentiation. Mesothelial cells are distinct in that they line somatic cavities, facilitating the smooth movement of organs, but are not exposed to the external environment. Malignant mesothelioma, or simply mesothelioma, develops either in the pleural, peritoneal or pericardial cavities, or in the tunica vaginalis testes. Mesothelioma has been a relatively rare cancer but is socially important due to its association with asbestos exposure, caused by modern industrial development. The major pathogenic mechanisms include oxidative stress either via catalytic reactions against the asbestos surface or frustrated phagocytosis of macrophages, and specific adsorption of hemoglobin and histones by asbestos fibers in the presence of phagocytic activity of mesothelial cells. Multiwall carbon nanotubes of ~50 nm-diameter, additionally adsorbing transferrin, are similarly carcinogenic to mesothelial cells in rodents and were thus classified as Group 2B carcinogens. Genetic alterations found in human and rat mesothelioma notably contain changes found in other excess iron-induced carcinogenesis models. Phlebotomy and iron chelation therapies have been successful in the prevention of mesothelioma in rats. Alternatively, loading of oxidative stress by non-thermal plasma to mesothelioma cells causes ferroptosis. Therefore, carcinogenesis by foreign fibrous inorganic materials may overlap the uncovered molecular mechanisms of birth of life and its evolution.}, } @article {pmid30309369, year = {2018}, author = {Smeele, P and d'Almeida, SM and Meiller, C and Chéné, AL and Liddell, C and Cellerin, L and Montagne, F and Deshayes, S and Benziane, S and Copin, MC and Hofman, P and Le Pimpec-Barthes, F and Porte, H and Scherpereel, A and Grégoire, M and Jean, D and Blanquart, C}, title = {Brain-derived neurotrophic factor, a new soluble biomarker for malignant pleural mesothelioma involved in angiogenesis.}, journal = {Molecular cancer}, volume = {17}, number = {1}, pages = {148}, pmid = {30309369}, issn = {1476-4598}, mesh = {Biomarkers, Tumor ; Brain-Derived Neurotrophic Factor/*blood/genetics ; Gene Expression ; Humans ; Lung Neoplasms/*blood/genetics/mortality/*pathology ; Mesothelioma/*blood/genetics/mortality/*pathology ; Mesothelioma, Malignant ; Neovascularization, Pathologic/*blood ; Pleural Effusion, Malignant/genetics/metabolism ; Pleural Neoplasms/*blood/genetics/mortality/*pathology ; Prognosis ; RNA, Messenger/genetics ; ROC Curve ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer related to asbestos exposure. The discovery of soluble biomarkers with diagnostic/prognostic and/or therapeutic properties would improve therapeutic care of MPM patients. Currently, soluble biomarkers described present weaknesses preventing their use in clinic. This study aimed at evaluating brain-derived neurotrophic factor (BDNF), we previously identified using transcriptomic approach, in MPM. We observed that high BDNF expression, at the mRNA level in tumors or at the protein level in pleural effusions (PE), was a specific hallmark of MPM samples. This protein presented significant but limited diagnostic properties (area under the curve (AUC) = 0.6972, p < 0.0001). Interestingly, high BDNF gene expression and PE concentration were predictive of shorter MPM patient survival (13.0 vs 8.3 months, p < 0.0001, in PE). Finally, BDNF did not affect MPM cell oncogenic properties but was implicated in PE-induced angiogenesis. In conclusion, BDNF appears to be a new interesting biomarker for MPM and could also be a new therapeutic target regarding its implication in angiogenesis.}, } @article {pmid30309285, year = {2018}, author = {Funahashi, S and Okazaki, Y and Nishiyama, T and Ohyoshi, H and Yasui, H and Nishida, K and Matsui, S and Toyokuni, S}, title = {Global overexpression of divalent metal transporter 1 delays crocidolite-induced mesothelial carcinogenesis in male mice.}, journal = {Free radical research}, volume = {52}, number = {9}, pages = {1030-1039}, doi = {10.1080/10715762.2018.1514604}, pmid = {30309285}, issn = {1029-2470}, mesh = {Animals ; Asbestos, Crocidolite/*toxicity ; Carcinogenesis/drug effects/*genetics ; Cation Transport Proteins/*genetics ; Epithelial Cells ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Iron ; Lung Neoplasms/chemically induced/*genetics/pathology ; Mesothelioma/chemically induced/*genetics/pathology ; Mesothelioma, Malignant ; Mice ; Mice, Transgenic ; }, abstract = {Exposure to asbestos fiber is central to mesothelial carcinogenesis, for which iron overload in or near mesothelial cells is a key pathogenic mechanism. Alternatively, iron chelation therapy with deferasirox or regular phlebotomy was significantly preventive against crocidolite-induced mesothelial carcinogenesis in rats. However, the role of iron transporters during asbestos-induced carcinogenesis remains elusive. Here, we studied the role of divalent metal transporter 1 (DMT1; Slc11a2), which is a Fe(II) transporter, that is present not only on the apical plasma membrane of duodenal cells but also on the lysosomal membrane of every cell, in crocidolite-induced mesothelial carcinogenesis using DMT1 transgenic (DMT1Tg) mice. DMT1Tg mice show mucosal block of iron absorption without cancer susceptibility under normal diet. We unexpectedly found that superoxide production was significantly decreased upon stimulation with crocidolite both in neutrophils and macrophages of DMT1Tg mice, and the macrophage surface revealed higher iron content 1 h after contact with crocidolite. Intraperitoneal injection of 3 mg crocidolite ultimately induced malignant mesothelioma in ∼50% of both wild-type and DMT1Tg mice (23/47 and 14/28, respectively); this effect was marginally (p = 0.069) delayed in DMT1Tg mice, promoting survival. The promotional effect of nitrilotriacetic acid was limited, and the liver showed significantly higher iron content both in DMT1Tg mice and after crocidolite exposure. The results indicate that global DMT1 overexpression causes decreased superoxide generation upon stimulation in inflammatory cells, which presumably delayed the promotional stage of crocidolite-induced mesothelial carcinogenesis. DMT1Tg mice with low-stamina inflammatory cells may be helpful to evaluate the involvement of inflammation in various pathologies.}, } @article {pmid30301262, year = {2018}, author = {Sarun, KH and Lee, K and Williams, M and Wright, CM and Clarke, CJ and Cheng, NC and Takahashi, K and Cheng, YY}, title = {Genomic Deletion of BAP1 and CDKN2A Are Useful Markers for Quality Control of Malignant Pleural Mesothelioma (MPM) Primary Cultures.}, journal = {International journal of molecular sciences}, volume = {19}, number = {10}, pages = {}, pmid = {30301262}, issn = {1422-0067}, mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics/*standards ; Cell Line, Tumor ; Cells, Cultured ; Cyclin-Dependent Kinase Inhibitor p16 ; Cyclin-Dependent Kinase Inhibitor p18/*genetics ; Gene Deletion ; Humans ; Lung Neoplasms/*genetics/pathology ; Male ; Mesothelioma/*genetics/pathology ; Mesothelioma, Malignant ; Middle Aged ; Primary Cell Culture/methods/*standards ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {Malignant pleural mesothelioma (MPM) is a deadly cancer that is caused by asbestos exposure and that has limited treatment options. The current standard of MPM diagnosis requires the testing of multiple immunohistochemical (IHC) markers on formalin-fixed paraffin-embedded tissue to differentiate MPM from other lung malignancies. To date, no single biomarker exists for definitive diagnosis of MPM due to the lack of specificity and sensitivity; therefore, there is ongoing research and development in order to identify alternative biomarkers for this purpose. In this study, we utilized primary MPM cell lines and tested the expression of clinically used biomarker panels, including CK8/18, Calretinin, CK 5/6, CD141, HBME-1, WT-1, D2-40, EMA, CEA, TAG72, BG8, CD15, TTF-1, BAP1, and Ber-Ep4. The genomic alteration of CDNK2A and BAP1 is common in MPM and has potential diagnostic value. Changes in CDKN2A and BAP1 genomic expression were confirmed in MPM samples in the current study using Fluorescence In situ Hybridization (FISH) analysis or copy number variation (CNV) analysis with digital droplet PCR (ddPCR). To determine whether MPM tissue and cell lines were comparable in terms of molecular alterations, IHC marker expression was analyzed in both sample types. The percentage of MPM biomarker levels showed variation between original tissue and matched cells established in culture. Genomic deletions of BAP1 and CDKN2A, however, showed consistent levels between the two. The data from this study suggest that genomic deletion analysis may provide more accurate biomarker options for MPM diagnosis.}, } @article {pmid30300743, year = {2019}, author = {White, R and Pulford, E and Elliot, DJ and Thurgood, LA and Klebe, S}, title = {Quantitative mass spectrometry to identify protein markers for diagnosis of malignant pleural mesothelioma.}, journal = {Journal of proteomics}, volume = {192}, number = {}, pages = {374-382}, doi = {10.1016/j.jprot.2018.09.018}, pmid = {30300743}, issn = {1876-7737}, mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Disease-Free Survival ; Female ; Humans ; Male ; Mass Spectrometry ; *Mesothelioma/metabolism/mortality ; Middle Aged ; Neoplasm Proteins/*metabolism ; *Pleural Effusion, Malignant/metabolism/mortality ; Survival Rate ; Vascular Endothelial Growth Factor A/*metabolism ; }, abstract = {Malignant pleural mesothelioma (MPM) is a devastating malignancy with a prognosis of <12 months. Even with bans on the use of asbestos in most Western countries, the incidence is still increasing due to the long latency periods between exposure and development of the disease. Diagnosis is often delayed due to invasive biopsies and lack of distinguishable markers. Patients frequently present with pleural effusions months to years before a radiologically detectable mass appears. This study aimed to investigate the proteome of pleural effusions taken from patients with MPM, adenocarcinoma and benign conditions in an attempt to identify a biomarker for early diagnosis. We identified several proteins that may be possible targets and warrant further investigation. Due to the predominance of up regulated proteins involved in VEGF signalling in MPM, we analysed VEGFA levels in effusions and found a strong correlation between VEGFA levels and survival in MPM.}, } @article {pmid30296019, year = {2018}, author = {Behrens, MA}, title = {Asbestos Trust Transparency.}, journal = {Fordham law review}, volume = {87}, number = {1}, pages = {107-124}, pmid = {30296019}, issn = {0015-704X}, mesh = {Asbestos/*adverse effects ; Asbestos, Amphibole/*adverse effects ; Asbestosis/etiology ; Bankruptcy ; Humans ; Liability, Legal/*economics ; Mesothelioma/etiology ; Occupational Exposure/*legislation & jurisprudence ; *Truth Disclosure ; United States ; }, } @article {pmid30293912, year = {2018}, author = {Mlika, M and Lamzirbi, O and Limam, M and Mejri, N and Ben Saad, S and Chaouch, N and Ben Miled, K and Marghli, A and Mezni, F}, title = {[Clinical and pathological profile of the pleural malignant mesothelioma: A retrospective study about 30 cases].}, journal = {Revue de pneumologie clinique}, volume = {74}, number = {6}, pages = {427-435}, doi = {10.1016/j.pneumo.2018.06.004}, pmid = {30293912}, issn = {1776-2561}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Incidence ; Lung Neoplasms/diagnosis/*epidemiology/pathology ; Male ; Mesothelioma/diagnosis/*epidemiology/pathology ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/diagnosis/*epidemiology/pathology ; Retrospective Studies ; Tunisia/epidemiology ; Young Adult ; }, abstract = {BACKGROUND: The malignant pleural mesothelioma (MPM) is a rare tumour usually associated to asbestos exposure. The delay between the exposure and the occurrence of the cancer can reach 40 years. This caused the pick of incidence described in many countries including Tunisia. The diagnosis is suspected based on clinical features but positive diagnosis is microscopic. Our aim was to describe the clinical and microscopic features of MPM through a single institution experience.

PATIENTS AND METHODS: We conducted a retrospective study about 30 MPM diagnosed over a 20-year-period (1995-2015). We included only patients with complete records including clinical, radiologic and microscopic features. All the microscopic diagnoses were reviewed by 2 pathologists. A mean of 12 slides per case was reviewed. The diagnosis was based on the 2015 WHO classification.

RESULTS: The mean age of the patients was 61 years, average 22 to 80 years. The sex ratio was 6,5. An asbetose exposition was reported in 21 cases. The most frequent symptoms was chest pain reported in 25 cases. Physical exam was normal in 9 cases. It revealed pleural syndorm in most patients (60 %). Imaging findings consisted mainly in diffuse pleural thickening in 17 cases. Twelve tumours were classified as stage I, 3 stage II, 14 stage III et 1 stage IV. Pleural biopsy was performed using needle in 18 cases, through thoracoscopy in 16 cases, thoracotomy in 3 cases and allowed the diagnosis in respectively 7 cases/18, 16 cases/16 and 3 cases/3. A lymph node biopsy was performed through mediastinoscopy in one case and yelded the diagnosis. The diagnosis was performed on surgical specimen in 2 patients: one bullectomy and one right upper lobectomy. The microscopic exam concluded to an EM in 17 cases, sarcomatoid mesothelioma (SM) in 4 cases and biphasic mesothelioma (BM) in 9 cases. Pan-cytokeratin antibody was used in all cases in association with 2 antibodies with positive diagnostic value and 2 antibodies with negative diagnostic value. It was repeated in 15 cases and the most used antibodies were the anti-calretinin and the TTF1. This was due to the lack of fixation in one case and in order to reach a quality criteria in the other cases. Surgical resection was possible in 2 patients. 15 patients were lost of view after a mean follow-up period of 3 months. Thirteen patients died before or during the follow-up.

CONCLUSION: This work was about a Tunisian experience in the diagnosis and management of MPM. The major limits faced were the incomplete databases, the small number of patients included. Microsocpic positive diagnosis necessitates a degree of expertise and every laboratory has to determine the most valuable antibodies through its experience in order to optimize the diagnosis and to reduce the delay of diagnosis.}, } @article {pmid30293239, year = {2018}, author = {van Gerwen, M and Wolf, A and Liu, B and Flores, R and Taioli, E}, title = {Short-term outcomes of pleurectomy decortication and extrapleural pneumonectomy in mesothelioma.}, journal = {Journal of surgical oncology}, volume = {118}, number = {7}, pages = {1178-1187}, doi = {10.1002/jso.25260}, pmid = {30293239}, issn = {1096-9098}, support = {NCI CCSG P30 CA196521//National Cancer Institute/ ; }, mesh = {Aged ; Arrhythmias, Cardiac/epidemiology ; Databases, Factual ; Female ; *Hospital Mortality ; Humans ; Male ; Mesothelioma/mortality/*surgery ; Middle Aged ; New York/epidemiology ; Pleura/*surgery ; Pleural Neoplasms/mortality/*surgery ; Pneumonectomy/*adverse effects ; Postoperative Complications ; Propensity Score ; }, abstract = {BACKGROUND/OBJECTIVES: We evaluated postoperative mortality and complications after extrapleural pneumonectomy (EPP) and pleurectomy decortication (P/D) to better understand their effectiveness in malignant pleural mesothelioma (MPM).

METHODS: A meta-analysis was done to evaluate 30-day mortality and postoperative complications. In addition, in-patients data of 500 eligible patients with MPM who underwent EPP or P/D was extracted from the New York Statewide Planning and Research Cooperative System (SPARCS). Multivariate analyses and propensity matching were used to compare in-hospital mortality and postoperative complications in EPP vs P/D.

RESULTS: The meta-analysis showed a statistically significant difference in 30-day mortality (5% [95% CI: 4-6] vs P/D 2% [95% CI: 1-3]), proportion of complications (46% [95% CI: 36-56] vs 24% [95% CI: 15-34]) and postoperative arrhythmias (20% [95% CI: 12-31] vs 5% [95% CI: 2-8]) for EPP vs P/D. In-hospital mortality (OR adj : 2.6; 95% CI: 0.86-7.75) and postoperative complications (OR adj : 1.1; 95% CI: 0.68-1.86) were not different in EPP compared with P/D while supraventricular arrhythmia was significantly more frequent after EPP vs P/D (OR adj : 5.2; 95% CI: 2.34-11.33).

CONCLUSIONS: Postoperative mortality, postoperative complications, and particularly supraventricular arrhythmia are less frequent after P/D vs EPP. P/D, a less invasive surgery, may provide a better option when technically feasible for patients with MPM.}, } @article {pmid30288361, year = {2018}, author = {Fear, VS and Tilsed, C and Chee, J and Forbes, CA and Casey, T and Solin, JN and Lansley, SM and Lesterhuis, WJ and Dick, IM and Nowak, AK and Robinson, BW and Lake, RA and Fisher, SA}, title = {Combination immune checkpoint blockade as an effective therapy for mesothelioma.}, journal = {Oncoimmunology}, volume = {7}, number = {10}, pages = {e1494111}, pmid = {30288361}, issn = {2162-4011}, abstract = {Mesothelioma is an aggressive asbestos induced cancer with extremely poor prognosis and limited treatment options. Immune checkpoint blockade (ICPB) has demonstrated effective therapy in melanoma and is now being applied to other cancers, including mesothelioma. However, the efficacy of ICPB and which immune checkpoint combinations constitute the best therapeutic option for mesothelioma have yet to be fully elucidated. Here, we used our well characterised mesothelioma tumour model to investigate the efficacy of different ICBP treatments to generate effective therapy for mesothelioma. We show that tumour resident regulatory T cell co-express high levels of CTLA-4, OX40 and GITR relative to T effector subsets and that these receptors are co-expressed on a large proportion of cells. Targeting any of CTLA-4, OX40 or GITR individually generated effective responses against mesothelioma. Furthermore, the combination of αCTLA-4 and αOX40 was synergistic, with an increase in complete tumour regressions from 20% to 80%. Other combinations did not synergise to enhance treatment outcomes. Finally, an early pattern in T cell response was predictive of response, with activation status and ICP receptor expression profile of T effector cells harvested from tumour and dLN correlating with response to immunotherapy. Taken together, these data demonstrate that combination ICPB can work synergistically to induce strong, durable immunity against mesothelioma in an animal model.}, } @article {pmid30281709, year = {2018}, author = {Kalinke, LP and Kalinke, MA and Sarquis, LMM and Marcondes, L and Halfeld, T and Mensi, C and Consonni, D}, title = {[A proposal for the creation of a system to monitor cases of malignant mesothelioma in Curitiba, Paraná, Brazil].}, journal = {Cadernos de saude publica}, volume = {34}, number = {9}, pages = {e00171917}, doi = {10.1590/0102-311X00171917}, pmid = {30281709}, issn = {1678-4464}, mesh = {Asbestos/*toxicity ; Brazil/epidemiology ; Carcinogens/*toxicity ; Disease Notification/*methods ; Environmental Exposure/*adverse effects ; *Hospital Records ; Humans ; Lung Neoplasms/*epidemiology/etiology ; Mesothelioma/*epidemiology/etiology ; Mesothelioma, Malignant ; }, abstract = {The study proposes the creation of a system to monitor cases of malignant mesothelioma in the municipality of Curitiba, Paraná State, Brazil, based on the Italian model. This diagnosis-type action-research project featured exploratory and planning phases conducted from July 2015 to May 2017. The following search tools were used: Hospital-Based Cancer Registries Integrator with specific morphologies for mesothelioma; Hospital-Based Cancer Registry with codes C38.4 and C45 of the International Classification of Diseases, 10th revision, and/or records coded by the ICD-O with topographies C38 and C48; Population-Based Cancer Registry of the Curitiba Municipal Health Department, with the same codes. The study also identified, analyzed, and adapted to the Brazilian reality the model, questionnaires, and registry software for mesothelioma from Lombardy, Italy. Fifteen cases of mesothelioma were recorded in the Hospital-Based Cancer Registries Integrator. Two cases were recorded in the University Hospital-Based Cancer Registry and 16 in the Cancer Hospital. There were 317 cases recorded in the Population-Based Cancer Registry during the same period. Although some information was complete, data were lacking on patients' occupational history, thereby preventing the determination of a causal nexus. Given a predicted increase in cases of mesothelioma in the coming decades and the response to court cases, the implementation of registries has become essential to facilitate knowledge and follow-up on the determination of the causal link and specific sources of asbestos exposure in the country.}, } @article {pmid30272283, year = {2018}, author = {Zhang, C and Hao, Y and Wu, L and Dong, X and Jiang, N and Cong, B and Liu, J and Zhang, W and Tang, D and De Perrot, M and Zhao, X}, title = {Curcumin induces apoptosis and inhibits angiogenesis in murine malignant mesothelioma.}, journal = {International journal of oncology}, volume = {53}, number = {6}, pages = {2531-2541}, pmid = {30272283}, issn = {1791-2423}, mesh = {Angiogenesis Inhibitors/*administration & dosage/pharmacology ; Animals ; Antineoplastic Agents/*administration & dosage/pharmacology ; Apoptosis Inducing Factor/metabolism ; Cell Cycle/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Curcumin/*administration & dosage/pharmacology ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Lung Neoplasms/blood supply/*drug therapy/metabolism ; Mesothelioma/blood supply/*drug therapy/metabolism ; Mesothelioma, Malignant ; Mice ; Signal Transduction/drug effects ; Xenograft Model Antitumor Assays ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare form of cancer that is associated with asbestos exposure. Unfortunately, current therapies have limited efficacy. Previous studies have indicated that curcumin exerts antiproliferative and antitumor effects, and has low toxicity. The present study aimed to evaluate the anticancer effects of curcumin on the RN5 MPM cell line. The inhibitory effects of curcumin on cell viability were determined using the sulforhodamine B assay. In addition, cell cycle progression was analyzed by propidium iodide (PI) staining and flow cytometry, and curcumin‑induced apoptosis was measured by Annexin V/PI double staining. The translocation of apoptosis-inducing factor (AIF) was assessed by western blotting and immunofluorescence, and the expression levels of the phosphoinositide 3-kinase (PI3K)-AKT serine/threonine kinase (Akt)‑mammalian target of rapamycin (mTOR) signaling pathway proteins and mitochondria-associated proteins were evaluated by western blotting. In vivo antitumor effects were evaluated in a subcutaneous murine model. Briefly, tumors were harvested from the mice, and immunohistochemistry was conducted to evaluate cell proliferation, apoptosis and angiogenesis. The results indicated that curcumin inhibited RN5 cell viability and induced apoptotic cell death. In addition the findings suggested that curcumin-induced cell apoptosis occurred via the mitochondrial pathway, and caspase‑independent and AIF-dependent pathways. Further analysis revealed that curcumin may act as a PI3K-Akt-mTOR signaling pathway inhibitor by downregulating PI3K, p-Akt, p-mTOR and p-p70 ribosomal protein S6 kinase. Furthermore, curcumin inhibited tumor angiogenesis in vivo. In conclusion, curcumin may be potent enough to be developed as a novel therapeutic agent for the treatment of MPM.}, } @article {pmid30266660, year = {2018}, author = {Tsao, AS and Lindwasser, OW and Adjei, AA and Adusumilli, PS and Beyers, ML and Blumenthal, GM and Bueno, R and Burt, BM and Carbone, M and Dahlberg, SE and de Perrot, M and Fennell, DA and Friedberg, J and Gill, RR and Gomez, DR and Harpole, DH and Hassan, R and Hesdorffer, M and Hirsch, FR and Hmeljak, J and Kindler, HL and Korn, EL and Liu, G and Mansfield, AS and Nowak, AK and Pass, HI and Peikert, T and Rimner, A and Robinson, BWS and Rosenzweig, KE and Rusch, VW and Salgia, R and Sepesi, B and Simone, CB and Sridhara, R and Szlosarek, P and Taioli, E and Tsao, MS and Yang, H and Zauderer, MG and Malik, SM}, title = {Current and Future Management of Malignant Mesothelioma: A Consensus Report from the National Cancer Institute Thoracic Malignancy Steering Committee, International Association for the Study of Lung Cancer, and Mesothelioma Applied Research Foundation.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {13}, number = {11}, pages = {1655-1667}, doi = {10.1016/j.jtho.2018.08.2036}, pmid = {30266660}, issn = {1556-1380}, mesh = {Consensus ; Humans ; Lung Neoplasms/pathology/*therapy ; Mesothelioma/pathology/*therapy ; Mesothelioma, Malignant ; National Cancer Institute (U.S.) ; United States ; }, abstract = {On March 28- 29, 2017, the National Cancer Institute (NCI) Thoracic Malignacy Steering Committee, International Association for the Study of Lung Cancer, and Mesothelioma Applied Research Foundation convened the NCI-International Association for the Study of Lung Cancer- Mesothelioma Applied Research Foundation Mesothelioma Clinical Trials Planning Meeting in Bethesda, Maryland. The goal of the meeting was to bring together lead academicians, clinicians, scientists, and the U.S. Food and Drug Administration to focus on the development of clinical trials for patients in whom malignant pleural mesothelioma has been diagnosed. In light of the discovery of new cancer targets affecting the clinical development of novel agents and immunotherapies in malignant mesothelioma, the objective of this meeting was to assemble a consensus on at least two or three practice-changing multimodality clinical trials to be conducted through NCI's National Clinical Trials Network.}, } @article {pmid30262573, year = {2018}, author = {Arnold, DT and De Fonseka, D and Perry, S and Morley, A and Harvey, JE and Medford, A and Brett, M and Maskell, NA}, title = {Investigating unilateral pleural effusions: the role of cytology.}, journal = {The European respiratory journal}, volume = {52}, number = {5}, pages = {}, doi = {10.1183/13993003.01254-2018}, pmid = {30262573}, issn = {1399-3003}, mesh = {Adenocarcinoma/complications/*diagnosis/epidemiology ; Aged ; Aged, 80 and over ; *Cytodiagnosis ; Female ; Humans ; Lung Neoplasms/complications/*diagnosis/epidemiology ; Male ; Mesothelioma/complications/*diagnosis/epidemiology ; Mesothelioma, Malignant ; Middle Aged ; Neoplasms/complications/*diagnosis/epidemiology ; Pleural Effusion, Malignant/*diagnosis/epidemiology/etiology ; Prospective Studies ; Sensitivity and Specificity ; Thoracentesis ; United Kingdom/epidemiology ; }, abstract = {The vast majority of undiagnosed unilateral pleural effusions have fluid sent for cytological analysis. Despite widespread use, there is uncertainty about its sensitivity to diagnose malignant pleural effusions (MPEs). Our aim was to ascertain the utility of cytology using a large prospective cohort.Consecutive patients presenting with an undiagnosed unilateral pleural effusion were recruited to this UK-based study. All had pleural fluid sent for cytological analysis. Cytological sensitivity was based on the final diagnosis at 12 months, confirmed by two consultants.Over 8 years, 921 patients were recruited, of which 515 had a MPE. Overall sensitivity of fluid cytology to diagnose malignancy was 46% (95% CI 42-58%). There was variation in sensitivity depending on cancer primary, with mesothelioma (6%) and haematological malignancies (40%) being significantly lower than adenocarcinomas (79%). MPEs secondary to ovarian cancer had high pick-up rates (95%). In asbestos-exposed males with exudative effusions, the risk of MPE was 60%, but cytological sensitivity was 11%.This is the largest prospective study of pleural fluid cytology and informs discussions with patients about the likely requirement for investigations following thoracentesis. In patients presenting with a clinical suspicion of mesothelioma, cytological sensitivity is low, so more definitive investigations could be performed sooner.}, } @article {pmid30259910, year = {2018}, author = {Ascoli, V and Murer, B and Nottegar, A and Luchini, C and Carella, R and Calabrese, F and Lunardi, F and Cozzi, I and Righi, L}, title = {What's new in mesothelioma.}, journal = {Pathologica}, volume = {110}, number = {1}, pages = {12-28}, pmid = {30259910}, issn = {0031-2983}, mesh = {Biomarkers, Tumor/*analysis ; Biopsy ; Humans ; Immunohistochemistry ; Lung Neoplasms/*diagnosis/pathology ; Mesothelioma/*diagnosis/pathology ; Mesothelioma, Malignant ; Neoplasm Grading ; Pleural Neoplasms/*diagnosis/pathology ; Prognosis ; }, abstract = {Malignant pleural mesothelioma is a neoplasm characterized by a very poor prognosis and medico-legal implications. Diagnosis, prognosis and therapy are often challenging and include several issues. Cytological diagnosis is frequently the first step of the diagnostic process, and although its sensitivity may be somewhat lower, diagnostic criteria should be taken into account. When effusion cytology is inconclusive for the diagnosis, tissue biopsies should be taken. Even if the morphologic criteria for deciding whether a mesothelial proliferation is a benign or a malignant process have been defined, the separation of benign from malignant mesothelial proliferation is often a difficult problem for the pathologist, particularly on small biopsies. Thirdly, when the diagnosis is made, despite many efforts have been made to identify possible new biomarkers for early diagnosis, prognostic stratification and also predictive tools should be defined. Nowadays, the main prognostic parameter is still represented by the histological subtype, having the epithelioid MPM a better outcome than the sarcomatoid or biphasic MPM. A nuclear grading system have been also proposed to stratify patient outcome. Reliable predictive biomarkers are still lacking in MPM and a personalized therapeutic concept is eagerly needed. Mesothelioma occurs mostly as sporadic cancer and the main risk factor is asbestos exposure, but it also occurs among blood relatives suggesting possible increased genetic susceptibility besides shared exposures. Recently the study of genetic predisposition syndrome raised new aspect in the occurrence of mesothelioma cases. This review summarize these most important issues.}, } @article {pmid30257964, year = {2019}, author = {Santarelli, L and Gaetani, S and Monaco, F and Bracci, M and Valentino, M and Amati, M and Rubini, C and Sabbatini, A and Pasquini, E and Zanotta, N and Comar, M and Neuzil, J and Tomasetti, M and Bovenzi, M}, title = {Four-miRNA Signature to Identify Asbestos-Related Lung Malignancies.}, journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology}, volume = {28}, number = {1}, pages = {119-126}, doi = {10.1158/1055-9965.EPI-18-0453}, pmid = {30257964}, issn = {1538-7755}, mesh = {Aged ; Asbestos/*toxicity ; Biomarkers, Tumor/blood ; Carcinogens/toxicity ; Carcinoma, Non-Small-Cell Lung/*chemically induced ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/*chemically induced ; Male ; Mesothelioma/*chemically induced ; Mesothelioma, Malignant ; MicroRNAs/*blood/genetics ; Middle Aged ; Sensitivity and Specificity ; }, abstract = {BACKGROUND: Altered miRNA expression is an early event upon exposure to occupational/environmental carcinogens; thus, identification of a novel asbestos-related profile of miRNAs able to distinguish asbestos-induced cancer from cancer with different etiology can be useful for diagnosis. We therefore performed a study to identify miRNAs associated with asbestos-induced malignancies.

METHODS: Four groups of patients were included in the study, including patients with asbestos-related (NSCLC[Asb]) and asbestos-unrelated non-small cell lung cancer (NSCLC) or with malignant pleural mesothelioma (MPM), and disease-free subjects (CTRL). The selected miRNAs were evaluated in asbestos-exposed population.

RESULTS: Four serum miRNAs, that is miR-126, miR-205, miR-222, and miR-520g, were found to be implicated in asbestos-related malignant diseases. Notably, increased expression of miR-126 and miR-222 were found in asbestos-exposed subjects, and both miRNAs are involved in major pathways linked to cancer development. Epigenetic changes and cancer-stroma cross-talk could induce repression of miR-126 to facilitate tumor formation, angiogenesis, and invasion.

CONCLUSIONS: This study indicates that miRNAs are potentially involved in asbestos-related malignancies, and their expression outlines mechanism(s) whereby miRNAs may be involved in an asbestos-induced pathogenesis.

IMPACT: The discovery of a miRNA panel for asbestos-related malignancies would impact on occupational compensation and may be utilized for screening asbestos-exposed populations.}, } @article {pmid30256306, year = {2018}, author = {Tomasallo, CD and Christensen, KY and Raymond, M and Creswell, PD and Anderson, HA and Meiman, JG}, title = {An Occupational Legacy: Malignant Mesothelioma Incidence and Mortality in Wisconsin.}, journal = {Journal of occupational and environmental medicine}, volume = {60}, number = {12}, pages = {1143-1149}, doi = {10.1097/JOM.0000000000001461}, pmid = {30256306}, issn = {1536-5948}, support = {U60 OH010898/OH/NIOSH CDC HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asbestos ; Case-Control Studies ; Construction Industry/statistics & numerical data ; Death Certificates ; Extraction and Processing Industry/statistics & numerical data ; Female ; Humans ; Incidence ; Industry/*statistics & numerical data ; Lung Neoplasms/*epidemiology/mortality ; Male ; Manufacturing Industry/statistics & numerical data ; Mesothelioma/*epidemiology/mortality ; Mesothelioma, Malignant ; Middle Aged ; Occupational Diseases/*epidemiology/mortality ; Occupational Exposure/*statistics & numerical data ; Peritoneal Neoplasms/*epidemiology/mortality ; Pleural Neoplasms/*epidemiology/mortality ; Registries ; Schools ; Teaching/statistics & numerical data ; Wisconsin/epidemiology ; Young Adult ; }, abstract = {OBJECTIVES: The aim of the study was to describe mesothelioma occurrence in Wisconsin from 1997 to 2013 by usual industry and occupation (I&O), including occupations generally considered low risk.

METHODS: Population-based rates and standardized incidence and mortality ratios were calculated. Two case-control analyses were designed to compare mesothelioma incidence and mortality in specific I&O groups with occurrence of (1) brain and central nervous system cancers and (2) other causes of death, using logistic regression.

RESULTS: Mesothelioma incidence and mortality were elevated in Wisconsin (SIRadj = 1.20 [1.13 to 1.28]; SMRadj = 1.30 [1.22 to 1.38]). Certain industry (construction, manufacturing) and occupation (construction and extraction) groups were associated with increased odds of mesothelioma, with some evidence of increased risk among teachers.

CONCLUSIONS: Forty years after the Occupational and Safety Health Act, mesothelioma incidence and mortality remain elevated in Wisconsin, with increased risk continuing for certain I&O groups.}, } @article {pmid30254313, year = {2018}, author = {Johnen, G and Burek, K and Raiko, I and Wichert, K and Pesch, B and Weber, DG and Lehnert, M and Casjens, S and Hagemeyer, O and Taeger, D and Brüning, T and , }, title = {Prediagnostic detection of mesothelioma by circulating calretinin and mesothelin - a case-control comparison nested into a prospective cohort of asbestos-exposed workers.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {14321}, pmid = {30254313}, issn = {2045-2322}, mesh = {Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Calbindin 2/*blood ; Case-Control Studies ; Cohort Studies ; Female ; GPI-Linked Proteins/*blood ; Humans ; Incidence ; Lung Neoplasms/*blood/chemically induced/diagnosis ; Male ; Mesothelin ; Mesothelioma/*blood/chemically induced/diagnosis ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/*adverse effects ; Prognosis ; Prospective Studies ; }, abstract = {Malignant mesothelioma (MM) is strongly associated with a previous asbestos exposure. To improve timely detection of MM in asbestos workers, better screening tools - like minimally-invasive biomarkers - are desirable. Between 2008 and 2018 2,769 patients with benign asbestos-related diseases were recruited to participate in annual screens. Using a nested case-control design the protein markers calretinin and mesothelin were determined by enzyme-linked immunosorbent assays in prediagnostic plasma samples of 34 MM cases as well as 136 matched controls from the cohort. Conditional on a pre-defined specificity of 98% for calretinin and 99% for mesothelin the markers reached individual sensitivities of 31% and 23%, respectively, when including the incident cases with samples taken between one and 15 months before diagnosis. The combination of both markers increased the sensitivity to 46% at 98% specificity. Marker complementation increased with earlier sampling. The marker combination improves the sensitivity of the individual markers, indicating a useful complementation and suggesting that additional markers may further improve the performance. This is the first prospective cohort study to evaluate a detection of MM by calretinin and its combination with mesothelin up to about a year before clinical diagnosis. Whether an earlier diagnosis will result in reduced mortality has yet to be demonstrated.}, } @article {pmid30241199, year = {2018}, author = {Boffetta, P and Malvezzi, M and Pira, E and Negri, E and La Vecchia, C}, title = {International Analysis of Age-Specific Mortality Rates From Mesothelioma on the Basis of the International Classification of Diseases, 10th Revision.}, journal = {Journal of global oncology}, volume = {4}, number = {}, pages = {1-15}, pmid = {30241199}, issn = {2378-9506}, support = {P30 ES023515/ES/NIEHS NIH HHS/United States ; }, mesh = {Age Factors ; Female ; Humans ; International Classification of Diseases/*standards ; Mesothelioma/*mortality ; Mortality ; }, abstract = {Past analyses of mortality data from mesothelioma relied on unspecific codes, such as pleural neoplasms. We calculated temporal trends in age-specific mortality rates in Canada, the United States, Japan, France, Germany, Italy, the Netherlands, Poland, the United Kingdom, and Australia on the basis of the 10th version of the International Classification of Diseases, which includes a specific code for mesothelioma. Older age groups showed an increase (in the United States, a weaker decrease) during the study period, whereas in young age groups, there was a decrease (in Poland, a weaker increase, starting, however, from low rates). Results were consistent between men and women and between pleural and peritoneal mesothelioma, although a smaller number of events in women and for peritoneal mesothelioma resulted in less precise results. The results show the heterogeneous effect of the reduction of asbestos exposure on different age groups; decreasing mortality in young people reflects reduced exposure opportunity, and increasing mortality in the elderly shows the long-term effect of early exposures.}, } @article {pmid30240694, year = {2018}, author = {Boffetta, P and Mundt, KA and Thompson, WJ}, title = {The epidemiologic evidence for elongate mineral particle (EMP)-related human cancer risk.}, journal = {Toxicology and applied pharmacology}, volume = {361}, number = {}, pages = {100-106}, doi = {10.1016/j.taap.2018.09.021}, pmid = {30240694}, issn = {1096-0333}, mesh = {Air Pollutants, Occupational/*toxicity ; Asbestos/toxicity ; Carcinogens/toxicity ; Humans ; Lung Neoplasms/chemically induced/epidemiology ; Mesothelioma/chemically induced/epidemiology ; Minerals/*toxicity ; Neoplasms/*chemically induced/*epidemiology ; Occupational Exposure ; Particulate Matter/*toxicity ; Risk Assessment ; }, abstract = {Epidemiologic research on the role of fibers and other elongate mineral particles (EMP) and human diseases including cancers has generated a large body of literature over the last decades: nevertheless, there remain some questions for which the scientific community appears unable to reach consensus. Reasons for genuine differences in opinion include (i) ways in which exposures have been classified; (ii) methodological limitations of the available studies, (iii) criteria for the interpretation of study results, including potential underlying biological mechanisms, and (iv) methodology for integrating the evidence. Various approaches have been proposed in recent years to address these issues, which will be illustrated using examples from asbestos, talc, taconite, synthetic mineral fibers and silicon carbide, with emphasis on potential carcinogenic effects. Potential solutions include improved exposure and outcome assessment - including use of biomarkers and other molecular approaches, consideration of potential confounding and other sources of bias, implementation of guidelines for study quality assessment and evidence evaluation and integration.}, } @article {pmid30209210, year = {2018}, author = {Finkelstein, MM}, title = {Response to: 'The epidemiology of malignant mesothelioma in women: gender differences and modalities of asbestos exposure' by Marinaccio et al.}, journal = {Occupational and environmental medicine}, volume = {75}, number = {11}, pages = {844}, doi = {10.1136/oemed-2018-105129}, pmid = {30209210}, issn = {1470-7926}, mesh = {*Asbestos ; Female ; Humans ; *Lung Neoplasms ; *Mesothelioma ; }, } @article {pmid30209209, year = {2018}, author = {Marinaccio, A and Corfiati, M and Binazzi, A and Di Marzio, D and Scarselli, A and Ferrante, P and Bonafede, M and Verardo, M and Mirabelli, D and Gennaro, V and Mensi, C and Schallemberg, G and Mazzoleni, G and Merler, E and Girardi, P and Negro, C and D'Agostin, F and Romanelli, A and Chellini, E and Silvestri, S and Pascucci, C and Calisti, R and Stracci, F and Romeo, E and Ascoli, V and Trafficante, L and Carrozza, F and Angelillo, I and Cavone, D and Cauzillo, G and Tallarigo, F and Tumino, R and Melis, M and Iavicoli, S and , }, title = {Letter concerning: 'Response to: 'The epidemiology of malignant mesothelioma in women: gender differences and modalities of asbestos exposure' by Marinaccio et al'.}, journal = {Occupational and environmental medicine}, volume = {75}, number = {11}, pages = {844-845}, doi = {10.1136/oemed-2018-105362}, pmid = {30209209}, issn = {1470-7926}, mesh = {*Asbestos ; Female ; Humans ; *Lung Neoplasms ; *Mesothelioma ; }, } @article {pmid30196105, year = {2018}, author = {Kharazmi, E and Chen, T and Fallah, M and Sundquist, K and Sundquist, J and Albin, M and Weiderpass, E and Hemminki, K}, title = {Familial risk of pleural mesothelioma increased drastically in certain occupations: A nationwide prospective cohort study.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {103}, number = {}, pages = {1-6}, doi = {10.1016/j.ejca.2018.07.139}, pmid = {30196105}, issn = {1879-0852}, mesh = {Adolescent ; Adult ; Cohort Studies ; Female ; Humans ; Lung Neoplasms/*etiology/pathology ; Male ; Mesothelioma/*etiology/pathology ; Mesothelioma, Malignant ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*etiology/pathology ; Prospective Studies ; Young Adult ; }, abstract = {OBJECTIVE: We aimed to explore the effect of occupation on familial risk of pleural mesothelioma in a nationwide cohort study design.

METHOD: The nationwide Swedish Family-Cancer Database includes all Swedes born after 1931 and their biological parents, totalling 16.1 million individuals with about 2.3 million cancer patients. Hazards ratios (HRs) were calculated adjusting for age, sex and region of residence.

RESULTS: Having asbestos-related occupation in the absence of family history of mesothelioma increased risk of mesothelioma more than threefold (adjusted HR = 3.2, 95% confidence interval [CI]: 3.0-3.5). In those who had a history of mesothelioma in their first-degree relatives and an asbestos-related occupation, risk of mesothelioma dramatically increased compared with individuals without such occupations and family history (without chronic obstructive pulmonary disease [COPD] HR = 24, 95% CI: 15-39; with COPD 45, 95% CI: 15-141). In those who had a family history of mesothelioma and no history of an asbestos-related occupation, risk of mesothelioma did not show significant increase compared with those who had no family history of mesothelioma and no asbestos-related occupation (HR = 1.6; 95% CI: 0.7-3.8).

CONCLUSION: First-degree relatives of patients with pleural mesothelioma had a drastic risk of developing this malignancy in case of certain occupations, which shows a gene-environment interaction is probable in risk of mesothelioma.}, } @article {pmid30174219, year = {2019}, author = {Marant Micallef, C and Shield, KD and Vignat, J and Baldi, I and Charbotel, B and Fervers, B and Gilg Soit Ilg, A and Guénel, P and Olsson, A and Rushton, L and Hutchings, SJ and Cléro, E and Laurier, D and Scanff, P and Bray, F and Straif, K and Soerjomataram, I}, title = {Cancers in France in 2015 attributable to occupational exposures.}, journal = {International journal of hygiene and environmental health}, volume = {222}, number = {1}, pages = {22-29}, doi = {10.1016/j.ijheh.2018.07.015}, pmid = {30174219}, issn = {1618-131X}, support = {001/WHO_/World Health Organization/International ; }, mesh = {Carcinogens/*toxicity ; Female ; France/epidemiology ; Humans ; Male ; Neoplasms/*chemically induced/epidemiology ; Occupational Exposure/*adverse effects/statistics & numerical data ; }, abstract = {BACKGROUND: Recent and comprehensive estimates for the number of new cancer cases in France attributable to occupational exposures are lacking.

OBJECTIVES: To estimate the number of new cancer cases attributable to occupational exposures, using a newly developed methodology and the most recent data, for a comprehensive set of occupational carcinogens in France in 2015.

METHODS: Surveys among employees, the national labor force data, a cohort of agricultural workers, national monitoring of workers exposed to ionizing radiation and job-exposure matrix in France were used. The number and proportion of new cancer cases attributable to established occupational carcinogens (Group 1) was estimated using estimation of lifetime exposure and risk estimates from cohort studies. Cancer data were obtained from the French Cancer Registries Network.

RESULTS: In France in 2015, an estimated 7905 new cancer cases, 7336 among men and 569 among women, were attributable to occupational exposures, representing 2.3% of all new cancer cases (3.9% and 0.4% among men and women respectively). Among men and women, lung cancer was impacted the most, followed by mesothelioma and bladder cancer in men, and by mesothelioma and ovary in women. These cancers contributed to 89% of the total cancers attributable to occupational carcinogens in men, and to 80% in women. The main contributing occupational agent was asbestos among men (45%) and women (60%).

CONCLUSIONS: Currently, occupational exposures contribute to a substantial burden of cancer in France. Enhanced monitoring and implementation of protective labor policies could potentially prevent a large proportion of these cancers.}, } @article {pmid30169798, year = {2018}, author = {Terracini, B}, title = {Commentary: Past and current asbestos exposure and future mesothelioma risks in Britain.}, journal = {International journal of epidemiology}, volume = {47}, number = {6}, pages = {1756-1757}, doi = {10.1093/ije/dyy175}, pmid = {30169798}, issn = {1464-3685}, mesh = {Asbestos ; Humans ; *Lung Neoplasms ; *Mesothelioma ; United Kingdom ; }, } @article {pmid30158318, year = {2018}, author = {Reid, A and Franklin, P and Berry, G and Peters, S and Sodhi-Berry, N and Brims, F and Musk, AW and de Klerk, NH}, title = {Are children more vulnerable to mesothelioma than adults? A comparison of mesothelioma risk among children and adults exposed non-occupationally to blue asbestos at Wittenoom.}, journal = {Occupational and environmental medicine}, volume = {75}, number = {12}, pages = {898-903}, doi = {10.1136/oemed-2018-105108}, pmid = {30158318}, issn = {1470-7926}, mesh = {Adolescent ; Adult ; Age Distribution ; Asbestos, Crocidolite/*toxicity ; Child ; Child, Preschool ; Environmental Exposure/*adverse effects ; Female ; Humans ; Incidence ; Infant ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Proportional Hazards Models ; Sex Distribution ; Western Australia/epidemiology ; Young Adult ; }, abstract = {OBJECTIVES: The presence of asbestos in public buildings is a legacy of past asbestos use in many developed countries. Of particular concern is the amount and current condition in schools and the vulnerability of children to mesothelioma. Our aim was to compare the risk of mesothelioma between those exposed to blue asbestos as children and as adults at Wittenoom.

METHODS: Public sources were used to establish the Wittenoom residents' cohort. Mesothelioma incidence rates per 100 000 person-years at risk were derived for those first exposed to asbestos at Wittenoom as children (<15 years) or adults separately. Proportional hazards survival models examined the slope of the exposure-response relationship between asbestos exposure and incidence of mesothelioma in different sex and age groups.

RESULTS: The mesothelioma rate was lower among those first exposed as children (76.8 per 100 000) than those first exposed as adults (121.3 per 100 000). Adjusting for cumulative exposure to asbestos and sex, those exposed as adults had a greater risk of mesothelioma (adjusted HR 2.5, 95% CI 1.7 to 3.7). The slope of the exposure-response relationship did not differ between those exposed as children and those exposed as adults.

CONCLUSION: We found no greater susceptibility to mesothelioma among those first exposed to asbestos as children than those first exposed as adults. However, given the long latency of mesothelioma, and the greater years of life yet to be lived by the Wittenoom children, it is likely that there will be more cases of mesothelioma in the future among those first exposed as children.}, } @article {pmid30157247, year = {2018}, author = {Rath, EM and Cheng, YY and Pinese, M and Sarun, KH and Hudson, AL and Weir, C and Wang, YD and Håkansson, AP and Howell, VM and Liu, GJ and Reid, G and Knott, RB and Duff, AP and Church, WB}, title = {BAMLET kills chemotherapy-resistant mesothelioma cells, holding oleic acid in an activated cytotoxic state.}, journal = {PloS one}, volume = {13}, number = {8}, pages = {e0203003}, pmid = {30157247}, issn = {1932-6203}, mesh = {Animals ; Antineoplastic Agents/chemistry/*pharmacology ; Cell Line, Tumor ; Cell Membrane/drug effects/metabolism ; Cell Survival/drug effects ; Drug Resistance, Neoplasm/*drug effects ; Humans ; Hydrogen-Ion Concentration ; Lactalbumin/chemistry/*pharmacology ; Lung Neoplasms/*pathology ; Mesothelioma/*pathology ; Mesothelioma, Malignant ; Mitochondrial Proton-Translocating ATPases/metabolism ; Models, Molecular ; Molecular Conformation ; Oleic Acid/chemistry/*pharmacology ; }, abstract = {Malignant pleural mesothelioma is an aggressive cancer with poor prognosis. Here we have investigated in vitro efficacy of BAMLET and BLAGLET complexes (anti-cancer complexes consisting of oleic acid and bovine α-lactalbumin or β-lactoglobulin respectively) in killing mesothelioma cells, determined BAMLET and BLAGLET structures, and investigated possible biological mechanisms. We performed cell viability assays on 16 mesothelioma cell lines. BAMLET and BLAGLET having increasing oleic acid content inhibited human and rat mesothelioma cell line proliferation at decreasing doses. Most of the non-cancer primary human fibroblasts were more resistant to BAMLET than were human mesothelioma cells. BAMLET showed similar cytotoxicity to cisplatin-resistant, pemetrexed-resistant, vinorelbine-resistant, and parental rat mesothelioma cells, indicating the BAMLET anti-cancer mechanism may be different to drugs currently used to treat mesothelioma. Cisplatin, pemetrexed, gemcitabine, vinorelbine, and BAMLET, did not demonstrate a therapeutic window for mesothelioma compared with immortalised non-cancer mesothelial cells. We demonstrated by quantitative PCR that ATP synthase is downregulated in mesothelioma cells in response to regular dosing with BAMLET. We sought structural insight for BAMLET and BLAGLET activity by performing small angle X-ray scattering, circular dichroism, and scanning electron microscopy. Our results indicate the structural mechanism by which BAMLET and BLAGLET achieve increased cytotoxicity by holding increasing amounts of oleic acid in an active cytotoxic state encapsulated in increasingly unfolded protein. Our structural studies revealed similarity in the molecular structure of the protein components of these two complexes and in their encapsulation of the fatty acid, and differences in the microscopic structure and structural stability. BAMLET forms rounded aggregates and BLAGLET forms long fibre-like aggregates whose aggregation is more stable than that of BAMLET due to intermolecular disulphide bonds. The results reported here indicate that BAMLET and BLAGLET may be effective second-line treatment options for mesothelioma.}, } @article {pmid30156102, year = {2018}, author = {Felley-Bosco, E and MacFarlane, M}, title = {Asbestos: Modern Insights for Toxicology in the Era of Engineered Nanomaterials.}, journal = {Chemical research in toxicology}, volume = {31}, number = {10}, pages = {994-1008}, doi = {10.1021/acs.chemrestox.8b00146}, pmid = {30156102}, issn = {1520-5010}, support = {MC_U132685863/MRC_/Medical Research Council/United Kingdom ; MC_UU_00025/4/MRC_/Medical Research Council/United Kingdom ; MC_UU_00025/5/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Air Pollutants/toxicity ; Asbestos/*toxicity ; Cyclin-Dependent Kinase Inhibitor p16/genetics/metabolism ; Female ; Humans ; Lung Neoplasms/*etiology/mortality ; Male ; Mesothelioma/*etiology/mortality ; Mutation ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics/metabolism ; Nanostructures/*chemistry ; Survival Rate ; Tumor Suppressor Protein p53/genetics/metabolism ; Tumor Suppressor Proteins/genetics/metabolism ; Ubiquitin Thiolesterase/genetics/metabolism ; }, abstract = {Asbestos fibers are naturally occurring silicates that have been extensively used in the past, including house construction, but because of their toxicity, their use has been banned in 63 countries. Despite this, more than one million metric tons of asbestos are still consumed annually in countries where asbestos use has not been banned. Asbestos-related disease incidence is still increasing in several countries, including those countries that banned the use of asbestos more than 30 years ago. We highlight here recent knowledge obtained in experimental models about the mechanisms leading to tumor development following asbestos exposure, including genetic and epigenetic changes. Importantly, the landscape of alterations observed experimentally in tumor samples is consistent with alterations observed in clinical tumor samples; therefore, studies performed on early/precancer stages should help inform secondary prevention, which remains crucial in the absence of an efficient primary prevention. Knowledge gathered on asbestos should also help address future challenges, especially in view of the increased production of new materials that may behave similarly to asbestos fibers.}, } @article {pmid30144378, year = {2019}, author = {Muscella, A and Cossa, LG and Vetrugno, C and Antonaci, G and Marsigliante, S}, title = {ADP sensitizes ZL55 cells to the activity of cisplatin.}, journal = {Journal of cellular physiology}, volume = {234}, number = {4}, pages = {4409-4417}, doi = {10.1002/jcp.27224}, pmid = {30144378}, issn = {1097-4652}, mesh = {Adenosine Triphosphate/*pharmacology ; Antineoplastic Combined Chemotherapy Protocols/*pharmacology ; Apoptosis/drug effects ; Caspases/metabolism ; Cell Cycle Checkpoints/drug effects ; Cell Line, Tumor ; Cell Proliferation/*drug effects ; Cisplatin/*pharmacology ; Dose-Response Relationship, Drug ; Drug Resistance, Neoplasm ; Humans ; Lung Neoplasms/*drug therapy/genetics/metabolism/pathology ; Mesothelioma/*drug therapy/genetics/metabolism/pathology ; Mesothelioma, Malignant ; Phosphorylation ; Poly (ADP-Ribose) Polymerase-1/metabolism ; Ribosomal Protein S6 Kinases/metabolism ; Signal Transduction ; Sirolimus/pharmacology ; TOR Serine-Threonine Kinases/antagonists & inhibitors/metabolism ; Tumor Suppressor Protein p53/genetics/metabolism ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive malignant tumor in which cisplatin therapy is commonly used, although its effectiveness is limited. It follows that research efforts dedicated to identify promising combinations that can synergistically kill cancer cells are needed. Because we recently demonstrated that ADP inhibits the proliferation of ZL55 cells, an MPM-derived cell line obtained from bioptic samples of asbestos-exposed patients. Our objective in this study was to investigate the hypothesis that ADP also potentiates the cytotoxic activity of cisplatin. Results show that in ZL55 cells ADP enhanced (a) the cytotoxicity of cisplatin by 12-fold, (b) the restraint of cell clonogenic potential cisplatin-mediated, and (c) the number of apoptotic cells. Cisplatin, but not ADP, caused caspases activation; nevertheless, poly(ADP-ribose) polymerase-1 was not only cleaved in cisplatin-treated cells but also in cells treated with ADP alone. Furthermore, ADP, but not cisplatin, decreased mTOR and 6SK phosphorylations. Both ADP and cisplatin increased p53 protein, but ADP was also able to enhance p53 messenger RNA. P53 silencing resulted in a very large decrement of cell death induced by ADP or by cisplatin and reverted ADP effects on mTOR/S6K phosphorylation, suggesting that activated p53 may act as a negative regulator of mTOR. Consistently, the inhibition of mTOR by rapamycin also sensitized cells to cisplatin, and the effects of cisplatin plus rapamycin were identical to those obtained with cisplatin plus ADP. These findings suggest that the combination of ADP and cisplatin may be a promising strategy for the clinical treatment of cisplatin-resistant MPM.}, } @article {pmid30140191, year = {2018}, author = {Kang, DM and Kim, JE and Kim, YK and Lee, HH and Kim, SY}, title = {Occupational Burden of Asbestos-Related Diseases in Korea, 1998-2013: Asbestosis, Mesothelioma, Lung Cancer, Laryngeal Cancer, and Ovarian Cancer.}, journal = {Journal of Korean medical science}, volume = {33}, number = {35}, pages = {e226}, pmid = {30140191}, issn = {1598-6357}, mesh = {Aged ; Asbestos/*adverse effects ; Asbestosis ; Europe ; Female ; Humans ; Laryngeal Neoplasms ; Lung Neoplasms ; Male ; Mesothelioma ; Middle Aged ; Occupational Diseases/*chemically induced ; Occupational Exposure ; Ovarian Neoplasms ; Republic of Korea ; }, abstract = {BACKGROUND: Asbestos exposure causes asbestos-related diseases (ARDs) including asbestosis, malignant mesothelioma, lung cancer, laryngeal cancer, and ovarian cancer. Although Korea used substantial amounts of asbestos in the past, no study has focused on its occupational burden of disease (OBD). Therefore, this study aimed to determine the OBDs of ARDs in Korea.

METHODS: The CARcinogen Exposure (CAREX) database was used to determine the proportion of exposed population. Relative risks for lung cancer, laryngeal cancer, and ovarian cancer were used to determine the population-attributable fraction. Data for deaths caused by ARDs during 1998-2013 were obtained from the World Health Organization mortality database. The potential years of life lost (PYLL) and annual average PYLL (APYLL) indicated OBDs.

RESULTS: In Korea, the number of ARD-attributable deaths and PYLL due to all ARDs during 1998-2013 were 4,492 and 71,763.7, respectively. The number of attributable deaths and PYLL due to asbestosis, malignant mesothelioma, lung cancer, laryngeal cancer, and ovarian cancer were 37 and 554.2, 808 and 15,877.0, 3,256 and 47,375.9, 120 and 1,605.5, and 271 and 6,331.1, respectively; additionally, the APYLL were 15.0, 19.7, 14.6, 13.4, and 23.4, respectively, and the average age at death was 70.4, 62.6, 69.1, 69.9, and 61.8, respectively. Our study showed that although the use of asbestos has ceased in Korea, the incidence of ARDs tends to increase.

CONCLUSION: Therefore, efforts to reduce future OBDs of ARDs, including early detection and proper management of ARDs, are needed in Korea.}, } @article {pmid30137349, year = {2018}, author = {Krupoves, A}, title = {Commentary: Asbestos exposure and mesothelioma risk.}, journal = {International journal of epidemiology}, volume = {47}, number = {6}, pages = {1758-1759}, doi = {10.1093/ije/dyy176}, pmid = {30137349}, issn = {1464-3685}, mesh = {Asbestos ; Humans ; *Lung Neoplasms ; *Mesothelioma ; United Kingdom ; }, } @article {pmid30137211, year = {2019}, author = {Farioli, A and Mattioli, S and Curti, S and Spatari, G and Violante, FS}, title = {Letter to the editor re: Dragani et al. (2018), 'Malignant mesothelioma diagnosed at a younger age is associated with heavier asbestos exposure'.}, journal = {Carcinogenesis}, volume = {40}, number = {3}, pages = {487}, doi = {10.1093/carcin/bgy111}, pmid = {30137211}, issn = {1460-2180}, mesh = {*Asbestos ; Humans ; *Lung Neoplasms ; *Mesothelioma ; }, } @article {pmid30134140, year = {2018}, author = {Chatfield, EJ}, title = {Measurement of elongate mineral particles: What we should measure and how do we do it?.}, journal = {Toxicology and applied pharmacology}, volume = {361}, number = {}, pages = {36-46}, doi = {10.1016/j.taap.2018.08.010}, pmid = {30134140}, issn = {1096-0333}, mesh = {Animals ; Asbestos, Amphibole/analysis ; Asbestos, Serpentine/analysis/toxicity ; Humans ; Lung Neoplasms/chemically induced/epidemiology ; Mesothelioma/chemically induced/epidemiology ; Mesothelioma, Malignant ; Microscopy, Electron, Transmission ; Mineral Fibers/*analysis/toxicity ; Minerals/*analysis/toxicity ; Occupational Exposure ; Particle Size ; Particulate Matter/*analysis/toxicity ; }, abstract = {The length distributions of single fibrils of Coalinga, UICC-B and wet dispersed chrysotile were measured by transmission electron microscopy (TEM). It was found that the distributions significantly diverged above approximately 10 μm (μm) in length, corresponding to differences in published results of animal experiments. This result is in contrast to published data in which counting of an insufficient number of fibers resulted in an erroneous conclusion that the length distribution of Coalinga chrysotile fibrils was indistinguishable from those of other sources of chrysotile. The size distributions of the respirable particle size fractions from acknowledged tremolite asbestos samples were found to be dominated by elongate particles longer than 5 μm that are within the dimensional range of non-asbestiform amphiboles. Prior studies have shown that these elongate particles obscure a correlation between a specific size range of particles and results of animal implantation studies that used tremolite of various morphologies. In the prior studies, a reference protocol was developed from four crushed non-asbestiform amphiboles to differentiate the size range of amphibole particles that correlates with the mesothelioma frequencies observed in the animal studies. In the work reported here, this correlation was tested with TEM analyses of amphiboles from Libby, MT, Sparta, NJ and Homestake mine, Lead, SD, which represent known environmental/occupational situations. Further TEM analyses of the tremolite samples used in the original animal implantation studies have also shown that the numbers of elongate tremolite particles with lengths ≤5 μm implanted into the animals are not correlated with the observed mesothelioma frequencies.}, } @article {pmid30133855, year = {2018}, author = {Finkelstein, MM}, title = {Letter Concerning: Glynn ME, Keeton KA, Gaffney SH, Sahmel J. Ambient Asbestos Fiber Concentrations and Long-Term Trends in Pleural Mesothelioma Incidence Between Urban and Rural Areas in the United States (1973-2012). Risk Analysis 2018;38(3):454-471.}, journal = {Risk analysis : an official publication of the Society for Risk Analysis}, volume = {38}, number = {8}, pages = {1521-1523}, doi = {10.1111/risa.13124}, pmid = {30133855}, issn = {1539-6924}, mesh = {*Asbestos ; Humans ; Incidence ; Lung Neoplasms ; *Mesothelioma ; Occupational Exposure ; Pleural Neoplasms ; United States ; }, } @article {pmid30133854, year = {2018}, author = {Keeton, KA and Glynn, ME and Gaffney, SH and Sahmel, J}, title = {Response to Letter to the Editor Regarding "Ambient Asbestos Fiber Concentrations and Long-Term Trends in Pleural Mesothelioma Incidence Between Urban and Rural Areas in the United States (1973-2012)" by Finkelstein.}, journal = {Risk analysis : an official publication of the Society for Risk Analysis}, volume = {38}, number = {8}, pages = {1524-1528}, doi = {10.1111/risa.13169}, pmid = {30133854}, issn = {1539-6924}, mesh = {*Asbestos ; Humans ; Incidence ; Lung Neoplasms ; *Mesothelioma ; Occupational Exposure ; Pleural Neoplasms ; United States ; }, } @article {pmid30126335, year = {2018}, author = {Egilman, D and Bird, T and Wilson, R}, title = {Use of Anti-Warnings to Falsely Reassure Downstream Users: An Asbestos Example.}, journal = {New solutions : a journal of environmental and occupational health policy : NS}, volume = {28}, number = {3}, pages = {515-538}, doi = {10.1177/1048291118794198}, pmid = {30126335}, issn = {1541-3772}, mesh = {Air Pollutants, Occupational/*adverse effects ; Asbestos/*adverse effects ; Asbestos, Serpentine/adverse effects ; *Communication ; Humans ; Industry/*organization & administration ; Mesothelioma/chemically induced ; Occupational Exposure/*adverse effects ; Safety ; Uncertainty ; }, abstract = {Product warnings are theoretically designed to reduce injuries associated with occupational, environmental, or consumer product exposures. Unfortunately, in an effort to protect sales, some companies have produced media and information to falsely reassure their customers about the risks associated with their products. These tactics have been termed "anti-warnings." We reviewed corporate documents uncovered in litigation alongside other historical publications to ascertain the types of anti-warnings used by Union Carbide Corporation (UCC) regarding their asbestos products. Our review finds that UCC went to great lengths to confuse their customers and make their particular asbestos product-which contained short-fiber, chrysotile asbestos-look safe. We discuss three primary communications methods UCC used: industry-produced publications, sales force direct communication with customers, and public speeches. These examples provide further insight into how corporations encourage uncertainty about the risks associated with their products. Understanding anti-warning methods is critical for the implementation of future policies that protect consumer, worker, and environmental health.}, } @article {pmid30123503, year = {2018}, author = {Bosio, M and Salvaterra, E and Datturi, F and Morbini, P and Zorzetto, M and Inghilleri, S and Tomaselli, S and Mangiarotti, P and Meloni, F and Cerveri, I and Stella, GM}, title = {5-hydroxymethylcytosine but not MTAP methylation status can stratify malignant pleural mesothelioma based on the lineage of origin.}, journal = {Multidisciplinary respiratory medicine}, volume = {13}, number = {}, pages = {27}, pmid = {30123503}, issn = {1828-695X}, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive tumor with poor prognosis, mainly associated with work or environmental exposure to asbestos. MPM's molecular profile is largerly unexplored and effective therapies are still lacking. MPM rarely harbours those somatic genetic lesions that usually characterize solid epithelial-derived tumors. On this basis, our study aims at investigating MPM epigenetic profile.

METHODS: We here assessed through immunohistochemistry, FISH and methylation specific PCR, the expression of 5-hydroxymethylcytosine (5- hmC) - an epigenetic marker and an important regulator of embryonic development and carcinogenesis - and the methylation status of the promoter of the MTAP gene - encoding for an enzyme involved in the rescue process of methionine and adenine - in two relevant series of FF-PE MPM samples derived from MPM thoracoscopic biopsies. Tissue sampling was performed at diagnosis.

RESULTS: Within the limitations of the study cohort, the 5-hmC immunophenotype was different among the histological MPM types analysed. In fact, 18% of the epithelial MPMs were negative, 47% weakly positive, and 35% of the cases showed an intense expression of 5-hmC. Sarcomatoid and biphasic MPMs showed intense 5-hmC expression pattern (positive and weakly positive in more than 80% of cases). Among MPM featuring epithelial lineage, none showed methylation of MTAP promoter.

CONCLUSIONS: Mesothelial sarcomatoid tumors featured a methylation profile characterized by a permanent gene silencing. Epithelial MPM methylation profile was in-between that of sarcomatoid MPM and the one of epithelial-derived tumors. MTAP promoter methylation level cannot be considered a suitable biomarker of epithelial MPM arousal.}, } @article {pmid30118736, year = {2019}, author = {Smith-Hannah, A and Naous, R}, title = {Primary peritoneal epithelioid mesothelioma of clear cell type with a novel VHL gene mutation: a case report.}, journal = {Human pathology}, volume = {83}, number = {}, pages = {199-203}, doi = {10.1016/j.humpath.2018.07.033}, pmid = {30118736}, issn = {1532-8392}, mesh = {Female ; Humans ; Mesothelioma/*genetics/*pathology ; Middle Aged ; Mutation ; Peritoneal Neoplasms/*genetics/*pathology ; Von Hippel-Lindau Tumor Suppressor Protein/*genetics ; }, abstract = {Clear cell variant of epithelioid mesothelioma is an extremely rare tumor with only isolated cases reported so far in the peritoneum. Here, we report a case of peritoneal epithelioid mesothelioma, clear cell variant, in a 63-year-old female patient with a novel VHL gene mutation and an unusual indolent clinical course. The patient, who has no clinical history of asbestos exposure, presented with a 27.2-cm upper abdominal mass and a 5.5-cm liver lesion. Retrospective review of the patient's abdominal computed tomographic scan 4 years ago showed 2 small abdominal lesions that were felt clinically to represent hemangiomas. These were retrospectively considered to have grown in size and represented the current abdominal mass. Both masses were subsequently biopsied and showed a proliferation of monomorphic epithelioid cells with distinct cell membranes, fine chromatin, and clear to finely vacuolated pale eosinophilic cytoplasm arranged in nests and solid sheets. Immunohistochemical staining confirmed it to be malignant mesothelioma. Clear cell variant of peritoneal epithelioid mesothelioma should always be considered in patients with an abdominal or pelvic mass with clear cell features. Given the rarity of such entity, its clinical course and prognosis remains unclear.}, } @article {pmid30113886, year = {2018}, author = {Panou, V and Gadiraju, M and Wolin, A and Weipert, CM and Skarda, E and Husain, AN and Patel, JD and Rose, B and Zhang, SR and Weatherly, M and Nelakuditi, V and Knight Johnson, A and Helgeson, M and Fischer, D and Desai, A and Sulai, N and Ritterhouse, L and Røe, OD and Turaga, KK and Huo, D and Segal, J and Kadri, S and Li, Z and Kindler, HL and Churpek, JE}, title = {Frequency of Germline Mutations in Cancer Susceptibility Genes in Malignant Mesothelioma.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {36}, number = {28}, pages = {2863-2871}, pmid = {30113886}, issn = {1527-7755}, support = {T35 DK062719/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Genetic Predisposition to Disease/genetics ; Germ-Line Mutation/*genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Lung Neoplasms/*genetics ; Male ; Mesothelioma/*genetics ; Mesothelioma, Malignant ; Middle Aged ; Young Adult ; }, abstract = {PURPOSE: The aim of the current study was to determine the prevalence and clinical predictors of germline cancer susceptibility mutations in patients with malignant mesothelioma (MM).

METHODS: We performed targeted capture and next-generation sequencing of 85 cancer susceptibility genes on germline DNA from 198 patients with pleural, peritoneal, and tunica vaginalis MM.

RESULTS: Twenty-four germline mutations were identified in 13 genes in 23 (12%) of 198 patients. BAP1 mutations were the most common (n = 6; 25%). The remaining were in genes involved in DNA damage sensing and repair (n = 14), oxygen sensing (n = 2), endosome trafficking (n = 1), and cell growth (n = 1). Pleural site (odds ratio [OR], 0.23; 95% CI, 0.10 to 0.58; P < .01), asbestos exposure (OR, 0.28; 95% CI, 0.11 to 0.72; P < .01), and older age (OR, 0.95; 95% CI, 0.92 to 0.99; P = .01) were associated with decreased odds of carrying a germline mutation, whereas having a second cancer diagnosis (OR, 3.33; 95% CI, 1.22 to 9.07; P = .02) significantly increased the odds. The odds of carrying a mutation in BAP1 (OR, 1,658; 95% CI, 199 to 76,224; P < .001), BRCA2 (OR, 5; 95% CI, 1.0 to 14.7; P = .03), CDKN2A (OR, 53; 95% CI, 6 to 249; P < .001), TMEM127 (OR, 88; 95% CI, 1.7 to 1,105; P = .01), VHL (OR, 51; 95% CI, 1.1 to 453; P = .02), and WT1 (OR, 20; 95% CI, 0.5 to 135; P = .049) were significantly higher in MM cases than in a noncancer control population. Tumor sequencing identified mutations in a homologous recombination pathway gene in 52% (n = 29 of 54).

CONCLUSION: A significant proportion of patients with MM carry germline mutations in cancer susceptibility genes, especially those with peritoneal MM, minimal asbestos exposure, young age, and a second cancer diagnosis. These data support clinical germline genetic testing for patients with MM and provide a rationale for additional investigation of the homologous recombination pathway in MM.}, } @article {pmid30111295, year = {2018}, author = {Löffler, MW and Steinhilber, J and Hilke, FJ and Haen, SP and Bösmüller, H and Montes-Mojarro, IA and Bonzheim, I and Stäbler, A and Faust, U and Grasshoff, U and Königsrainer, I and Rammensee, HG and Kanz, L and Königsrainer, A and Beckert, S and Riess, O and Schroeder, C}, title = {First case report of malignant peritoneal mesothelioma and oral verrucous carcinoma in a patient with a germline PTEN mutation: a combination of extremely rare diseases with probable further implications.}, journal = {BMC medical genetics}, volume = {19}, number = {1}, pages = {144}, pmid = {30111295}, issn = {1471-2350}, mesh = {Carcinoma, Verrucous/*genetics ; Germ-Line Mutation/*genetics ; Humans ; Lung Neoplasms/*genetics ; Mesothelioma/*genetics ; Mesothelioma, Malignant ; Mouth Neoplasms/*genetics ; PTEN Phosphohydrolase/*genetics ; Rare Diseases ; }, abstract = {BACKGROUND: The PTEN-hamartoma-tumor-syndrome (PHTS) is caused by germline mutations in Phosphatase and Tensin homolog (PTEN) and predisposes to the development of several typical malignancies. Whereas PTEN mutations have been implicated in the occurrence of malignant mesotheliomas, the genetic landscape of verrucous carcinomas (VC) is largely uncharted. Both VC and malignant peritoneal mesotheliomas (MPM) are exceedingly rare and a potential link between these malignancies and PHTS has never been reported.

CASE PRESENTATION: We here describe the clinical course of a PHTS patient who, in addition to a typical thyroid carcinoma at the age of 36 years, developed a highly-differentiated oral VC and an epithelioid MPM six years later. The patient with a history of occupational asbestos exposure underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for MPM. The clinical diagnosis of PHTS was consequently corroborated by a germline PTEN deletion. Sequencing of tumor tissue revealed a second hit in PTEN in the thyroid carcinoma and VC, confirmed by a PTEN loss and activation of the PI3K/AKT pathway in immunohistochemistry. Furthermore, additional somatic mutations in the thyroid carcinoma as well as in the VC were detected, whereas the genetics of MPM remained unrevealing.

DISCUSSION AND CONCLUSIONS: We here report the very unusual clinical course of a patient with rare tumors that have a germline mutation first hit in PTEN in common. Since this patient was exposed to asbestos and current evidence suggests molecular mechanisms that might render PHTS patients particularly susceptible to mesothelioma, we strongly recommend PHTS patients to avoid even minimal exposure.}, } @article {pmid30109162, year = {2018}, author = {Salazar, C and Kanter Md, N and Abboud, A}, title = {Malignant Pleural Mesothelioma, Biphasic Type: An Unusual and Insidious Case of Rapidly Progressive Small Blue Cell Tumor.}, journal = {Cureus}, volume = {10}, number = {6}, pages = {e2749}, pmid = {30109162}, issn = {2168-8184}, abstract = {Malignant pleural mesothelioma (MPM) is a rare neoplasm. It predominantly affects elderly individuals aged over 70 years presenting with a unilateral pleural tumor usually associated with previous asbestos exposure. The respiratory symptoms are associated with ipsilateral pleural involvement with concomitant pleural effusions. The diagnosis of MPM is established by the morphologic and immunohistochemical features of a cytologic specimen. MPM can present as three histologic subtypes: epithelioid, sarcomatoid, or biphasic. We present a case of an 85-year-old Caucasian female with a history of occupational asbestos exposure. She complained of 1-week history of progressive sharp right flank and scapular pain with mild shortness of breath, dry cough and pleuritic chest pain. CT of the chest showed a large loculated right pleural effusion with adjacent pleural thickening. CT abdomen and pelvis was negative for other neoplastic findings. CT-guided core biopsy of the right pleural-based mass was positive for a spindle to plasmacytoid small blue cell tumor. An extensive immunohistochemical panel was non-specific. A focal OSCAR keratin and WT-1 expression in the absence of carcinoma markers, a malignant mesothelioma, biphasic type was diagnosed. Further workup with PET-CT and cytotoxic chemotherapy combined with immunotherapy or tyrosine kinase inhibitors was recommended by oncology. The patient refused further imaging and treatment, and palliative care was consulted.}, } @article {pmid30104558, year = {2018}, author = {Krówczyńska, M and Wilk, E}, title = {Asbestos Exposure and the Mesothelioma Incidence in Poland.}, journal = {International journal of environmental research and public health}, volume = {15}, number = {8}, pages = {}, pmid = {30104558}, issn = {1660-4601}, mesh = {Asbestos/*adverse effects ; *Carcinogens ; Environmental Exposure/*statistics & numerical data ; Female ; Humans ; Incidence ; Lung Neoplasms/*epidemiology/*etiology ; Male ; Mesothelioma/*epidemiology/*etiology ; Mesothelioma, Malignant ; Poland/epidemiology ; Risk Factors ; }, abstract = {UNLABELLED: Asbestos is carcinogenic to humans; the exposure to asbestos causes a wide range of diseases.

AIM: Malignant mesothelioma (MM) is unique for asbestos exposure.

METHODS: Based on the physical inventory of asbestos-cement roofing, the social-economic situation of communes, the proximity of asbestos manufacturing plants, the land use data referring to the surface of the built-up area, and the historical data on the annexations, the amount of asbestos-containing products in use was estimated by computing best Random Forest models. Per capita asbestos use is an indicator to compare the state of asbestos use among countries. MM cases in the local administrative units (provinces) were tested by the application of Moran's I and Getis and Ord statistic.

RESULTS: The total amount of asbestos roofing in Poland was estimated at 738,068,000 m² (8.2 million tons). In total there were 28 plants in Poland located in 11 provinces throughout the country. The amount of asbestos-cement roofing in use is correlated primarily with the measurements of asbestos concentration fibers (rs = 0.597). MM raw morbidity rate was calculated, stratified by province, and classified into five groups with respect to incidence. Hotspots of MM cases are in the southern part of Poland.

CONCLUSIONS: MM cases are concentrated in the same geographical areas, which may indicate an increasing impact of environmental exposure. The results of the local and global autocorrelation clearly indicate a statistically significant relationship between incidences of MM in provinces. Poland and other Eastern European countries are among countries with low MM incidence rate. Detailed investigation is desirable since the current MM morbidity rate in Poland seems to be underestimated.}, } @article {pmid30101018, year = {2018}, author = {Negi, Y and Kuribayashi, K and Doi, H and Funaguchi, N and Koda, Y and Fujimoto, E and Mikami, K and Minami, T and Yokoi, T and Kijima, T}, title = {Double cancer comprising malignant pleural mesothelioma and squamous cell carcinoma of the lung treated with radiotherapy: A case report.}, journal = {Molecular and clinical oncology}, volume = {9}, number = {2}, pages = {181-186}, pmid = {30101018}, issn = {2049-9450}, abstract = {Pleurectomy/decortication (P/D) is the surgical treatment of choice for early malignant mesothelioma, but it remains unclear whether radiotherapy along with P/D should be used as multimodal treatment for this disease. We herein present the case of a 76-year-old man with a history of asbestos exposure who was diagnosed with left-sided malignant pleural mesothelioma in February 2010. The patient underwent chemotherapy with a combination of cisplatin and pemetrexed and achieved stable disease, after which time he was kept under observation. A positron emission tomography/computed tomography scan performed in February 2011 revealed nodular shadows with fluorodeoxyglucose uptake in S3 of the left lung; using bronchoscopy, the patient was diagnosed with stage IIB (cT3N0M0) primary squamous cell carcinoma. Chemoradiotherapy with vinorelbine and 60 Gy/20 fr radiotherapy was performed, and a partial response was obtained, suggesting that the radiotherapy used to treat the carcinoma of the lung may have also helped control the disease activity of the pre-existing mesothelioma. The present case indicates the value of radiotherapy in the treatment of malignant mesothelioma. The aim of the present study was to examine the possibility of new multimodal treatments for mesothelioma, along with a discussion of the relevant literature.}, } @article {pmid30098092, year = {2018}, author = {Aida, S and Aida, J and Naoi, M and Kato, M and Tsuura, Y and Natsume, I and Takubo, K}, title = {Measurement of telomere length in cells from pleural effusion: Asbestos exposure causes telomere shortening in pleural mesothelial cells.}, journal = {Pathology international}, volume = {68}, number = {9}, pages = {503-508}, doi = {10.1111/pin.12710}, pmid = {30098092}, issn = {1440-1827}, support = {JP C26460457//JSPS KAKENHI/ ; }, mesh = {Adenocarcinoma of Lung/pathology ; Adult ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Biomarkers, Tumor/*metabolism ; Female ; Humans ; Lung Neoplasms/*diagnosis/pathology ; Male ; Mesothelioma/*diagnosis/pathology ; Mesothelioma, Malignant ; Middle Aged ; Pleural Effusion/pathology ; Pleural Effusion, Malignant/*pathology ; Telomere/*pathology ; }, abstract = {We estimated the telomere lengths of neoplastic and non-neoplastic mesothelial cells and examined their correlation with asbestos exposure and the expression of markers of mesothelial malignancy. Cell blocks of pleural effusion obtained from 35 cases of non-neoplastic disease (NN), 12 cases of malignant mesothelioma (MM) and 12 cases of carcinomatous effusion due to lung adenocarcinoma (LA) were examined. Fifteen of the 35 NN cases had pleural plaques (NNpp+) suggestive of asbestos exposure, and the other 20 cases had no pleural plaques (NNpp-). Telomere length was measured using the tissue quantitative fluorescence in situ hybridization method, and expressed as normalized telomere-to-centromere ratio. NN cases had significantly longer telomeres than MM (P < 0.001) and LA (P < 0.001) cases. Telomeres in NNpp+ cases were slightly shorter than those of NNpp- cases (P = 0.047). MM and LA showed almost the same telomere length. NN cases with shorter telomeres tended to show aberrant expression of epithelial membrane antigen (EMA), CD146, glucose transporter 1 (GLUT1) and IGF-II messenger RNA-binding protein 3 (IMP3). These results suggest that telomere shortening and subsequent genetic instability play an important role in the development of MM. Measurement of telomere length of cells in pleural effusion might be helpful for earlier detection of MM.}, } @article {pmid30084369, year = {2018}, author = {Lucas, C}, title = {Miracle mineral or mesothelioma: cancer and asbestos in the USA.}, journal = {The Lancet. Oncology}, volume = {19}, number = {7}, pages = {868}, doi = {10.1016/S1470-2045(18)30352-8}, pmid = {30084369}, issn = {1474-5488}, mesh = {Asbestos/*adverse effects ; Humans ; Incidence ; Lung Neoplasms/epidemiology/etiology/physiopathology ; *Medicine in the Arts ; Mesothelioma/epidemiology/etiology/physiopathology ; Mesothelioma, Malignant ; *Motion Pictures ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*epidemiology/etiology/physiopathology ; United States/epidemiology ; }, } @article {pmid30077661, year = {2018}, author = {Garabrant, DH and Pastula, ST}, title = {A comparison of asbestos fiber potency and elongate mineral particle (EMP) potency for mesothelioma in humans.}, journal = {Toxicology and applied pharmacology}, volume = {361}, number = {}, pages = {127-136}, doi = {10.1016/j.taap.2018.07.003}, pmid = {30077661}, issn = {1096-0333}, mesh = {Air Pollutants, Occupational/*toxicity ; Aluminum Silicates/toxicity ; Asbestos/*toxicity ; Asbestos, Amosite/toxicity ; Asbestos, Amphibole/toxicity ; Asbestos, Crocidolite/toxicity ; Asbestos, Serpentine/toxicity ; Carcinogens/*toxicity ; Cohort Studies ; Humans ; Iron/toxicity ; Lung Neoplasms/etiology/*mortality ; Mesothelioma/etiology/*mortality ; Minerals/*toxicity ; Mining ; Occupational Exposure ; Particle Size ; Particulate Matter/*toxicity ; Silicates/toxicity ; Talc/toxicity ; }, abstract = {We analyzed the mesothelioma mortality in cohorts of workers exposed to crocidolite, amosite, and chrysotile to estimate asbestos fiber potency for mesothelioma, using the method of Hodgson and Darnton (2000). We relied on the original 17 cohort studies in their analysis, along with 3 updates of those studies and 3 new asbestos cohort studies published since 2000. We extended the analyses to examine the mesothelioma potency of tremolite in vermiculite from Libby, Montana, and for non-asbestiform elongate mineral particles (EMPs) in taconite iron ore, talc, and South Dakota gold mining. Mesothelioma potency (RMeso) was calculated as the percent of all expected deaths that were due to mesothelioma per fiber/cc-year of exposure.The RMeso was 0.0012 for chrysotile, 0.099 for amosite, and 0.451 for crocidolite: thus, the relative potency of chrysotile:amosite:crocidolite was 1:83:376, which was not appreciably different from the estimates by Hodgson and Darnton in 2000. The RMeso for taconite mining fibers was 0.069 which was slightly smaller than that for amosite. The RMeso for Libby fibers was 0.028 which was greater than that for chrysotile and less than that for amosite. Talc and gold mining EMPs were non-potent for mesothelioma. Although there are a number of methods for estimating fiber potency of asbestos and non-asbestiform EMPs, the method of Hodgson and Darnton provides a uniform method by which fiber potency can be compared across many fiber types. Our estimates of RMeso provide a useful addition to our knowledge of mesothelioma potency for different asbestos and non-asbestiform EMP fibers.}, } @article {pmid30072200, year = {2019}, author = {Lin, RT and Chang, YY and Wang, JD and Lee, LJ}, title = {Upcoming epidemic of asbestos-related malignant pleural mesothelioma in Taiwan: A prediction of incidence in the next 30 years.}, journal = {Journal of the Formosan Medical Association = Taiwan yi zhi}, volume = {118}, number = {1 Pt 3}, pages = {463-470}, doi = {10.1016/j.jfma.2018.07.013}, pmid = {30072200}, issn = {0929-6646}, mesh = {Adolescent ; Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Child ; Child, Preschool ; Environmental Exposure/*adverse effects ; Female ; *Forecasting ; Humans ; Incidence ; Infant ; Infant, Newborn ; Lung Neoplasms/chemically induced/*epidemiology ; Male ; Mesothelioma/chemically induced/*epidemiology ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/chemically induced/*epidemiology ; Regression Analysis ; Sex Distribution ; Taiwan/epidemiology ; Young Adult ; }, abstract = {BACKGROUND/PURPOSE: Globally, asbestos-related diseases (ARDs) keep rising over the coming decades. The epidemic of ARDs will be a burden on public health. We aimed to predict the malignant pleural mesothelioma (MPM) incidence in the next 30 years for Taiwan based on historical asbestos consumption.

METHODS: We collected annual data on local asbestos consumption during 1939-2015 and sex-specific incidence of pleural cancer as a proxy for MPM during 1979-2013. We applied Poisson log-linear models to predict future MPM numbers under the assumption that latency periods between asbestos exposure and MPM incidence were between 25 and 45 years.

RESULTS: Asbestos consumption reached a peak in the 1980s, with a total of 668 thousand metric tons during 1939-2015. The observed number of MPM incidence increased by 9- and 6-fold in males and females during 1979-2013, with a cumulative number of 907. Given a latency period of 31 years, MPM incidences were expected to peak around 2012-2016 for males and 2016-2020 for females. In 2017-2046, the predicted total number of new MPM might reach 659 cases (95% confidence interval = 579-749); and the male to female ratios ranged from 1.8 to 2.8.

CONCLUSION: The MPM epidemic in Taiwan will likely peak in 2012-2020 as a result of local asbestos consumption. Approximately 659 new MPM cases in the next 30 years warrant an urgent need to implement a total asbestos ban and put more resources on a comprehensive surveillance, diagnosis, and follow-up health care system for ARDs.}, } @article {pmid30060501, year = {2018}, author = {Sage, AP and Martinez, VD and Minatel, BC and Pewarchuk, ME and Marshall, EA and MacAulay, GM and Hubaux, R and Pearson, DD and Goodarzi, AA and Dellaire, G and Lam, WL}, title = {Genomics and Epigenetics of Malignant Mesothelioma.}, journal = {High-throughput}, volume = {7}, number = {3}, pages = {}, pmid = {30060501}, issn = {2571-5135}, abstract = {Malignant mesothelioma is an aggressive and lethal asbestos-related disease. Diagnosis of malignant mesothelioma is particularly challenging and is further complicated by the lack of disease subtype-specific markers. As a result, it is especially difficult to distinguish malignant mesothelioma from benign reactive mesothelial proliferations or reactive fibrosis. Additionally, mesothelioma diagnoses can be confounded by other anatomically related tumors that can invade the pleural or peritoneal cavities, collectively resulting in delayed diagnoses and greatly affecting patient management. High-throughput analyses have uncovered key genomic and epigenomic alterations driving malignant mesothelioma. These molecular features have the potential to better our understanding of malignant mesothelioma biology as well as to improve disease diagnosis and patient prognosis. Genomic approaches have been instrumental in identifying molecular events frequently occurring in mesothelioma. As such, we review the discoveries made using high-throughput technologies, including novel insights obtained from the analysis of the non-coding transcriptome, and the clinical potential of these genetic and epigenetic findings in mesothelioma. Furthermore, we aim to highlight the potential of these technologies in the future clinical applications of the novel molecular features in malignant mesothelioma.}, } @article {pmid30060470, year = {2018}, author = {Jean, D and Jaurand, MC}, title = {Mesotheliomas in Genetically Engineered Mice Unravel Mechanism of Mesothelial Carcinogenesis.}, journal = {International journal of molecular sciences}, volume = {19}, number = {8}, pages = {}, pmid = {30060470}, issn = {1422-0067}, mesh = {Animals ; *Animals, Genetically Modified ; Carcinogenesis/*genetics ; Epithelium/pathology ; Humans ; Lung/pathology ; Lung Neoplasms/*genetics ; Mesothelioma/*genetics ; Mesothelioma, Malignant ; *Mice ; Mutation ; Neoplasms, Experimental/*genetics ; Rats ; }, abstract = {Malignant mesothelioma (MM), a rare and severe cancer, mainly caused as a result of past-asbestos exposure, is presently a public health concern. Current molecular studies aim to improve the outcome of the disease, providing efficient therapies based on the principles of precision medicine. To model the molecular profile of human malignant mesothelioma, animal models have been developed in rodents, wild type animals and genetically engineered mice harbouring mutations in tumour suppressor genes, especially selecting genes known to be inactivated in human malignant mesothelioma. Animals were either exposed or not exposed to asbestos or to other carcinogenic fibres, to understand the mechanism of action of fibres at the molecular level, and the role of the selected genes in mesothelial carcinogenesis. The aim of the manuscript was to compare mesothelioma models to human malignant mesothelioma and to specify the clue genes playing a role in mesothelial carcinogenesis. Collectively, MM models recapitulate the clinical features of human MM. At least two altered genes are needed to induce malignant mesothelioma in mice. Two pathways regulated by Cdkn2a and Trp53 seem independent key players in mesothelial carcinogenesis. Other genes and pathways appear as bona fide modulators of the neoplastic transformation.}, } @article {pmid30049702, year = {2018}, author = {Lin, RT and Soeberg, MJ and Chien, LC and Fisher, S and Takala, J and Lemen, R and Driscoll, T and Takahashi, K}, title = {Bibliometric analysis of gaps in research on asbestos-related diseases: declining emphasis on public health over 26 years.}, journal = {BMJ open}, volume = {8}, number = {7}, pages = {e022806}, pmid = {30049702}, issn = {2044-6055}, mesh = {Asbestos/*adverse effects ; Asbestosis/*etiology ; Bibliometrics ; Biomedical Research/*trends ; China ; Finland ; Humans ; Italy ; Mesothelioma/*etiology ; Netherlands ; Public Health/trends ; }, abstract = {OBJECTIVES: The global burden of asbestos-related diseases (ARDs) is significant, and most of the world's population live in countries where asbestos use continues. We examined the gaps between ARD research and suggestions of WHO and the International Labour Organization on prevention.

METHODS: From the Web of Science, we collected data on all articles published during 1991-2016 and identified a subset of ARD-related articles. We classified articles into three research areas-laboratory, clinical and public health-and examined their time trends. For all and the top 11 countries publishing ARD-related articles, we calculated the proportions of all ARD-related articles that were in each of the three areas, the average rates of ARD-related articles over all articles, and the average annual per cent changes of rates.

RESULTS: ARD-related articles (n=14 284) accounted for 1.3‰ of all articles in 1991, but this had declined to 0.8‰ by 2016. Among the three research areas, the clinical area accounted for the largest proportion (65.0%), followed by laboratory (26.5%) and public health (24.9%). The public health area declined faster than the other areas, at -5.7% per year. Discrepancies were also observed among the top 11 countries regarding emphasis on public health research, with Finland and Italy having higher, and China and the Netherlands lower, emphases.

CONCLUSIONS: There is declining emphasis on the public health area in the ARD-related literature. Under the ongoing global situation of ARD, primary prevention will remain key for some time, warranting efforts to rectify the current trend in ARD-related research.}, } @article {pmid30032843, year = {2018}, author = {Rosskamp, M and De Schutter, H and Henau, K and Nackaerts, K and Van Meerbeeck, JP and Praet, M and Van Eycken, L}, title = {Assessing the completeness and correctness of the registration of malignant mesothelioma in Belgium.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {122}, number = {}, pages = {38-43}, doi = {10.1016/j.lungcan.2018.05.018}, pmid = {30032843}, issn = {1872-8332}, mesh = {Aged ; Asbestos/*adverse effects ; Belgium/epidemiology ; Cohort Studies ; *Databases, Factual ; Female ; Humans ; Lung Neoplasms/*epidemiology/mortality ; Male ; Mesothelioma/*epidemiology/mortality ; Mesothelioma, Malignant ; Middle Aged ; Registries/*statistics & numerical data ; Survival Analysis ; Survivors ; }, abstract = {OBJECTIVES: Malignant mesothelioma (MM) is a rare and aggressive cancer mostly caused by asbestos exposure, and for which the diagnosis is difficult. This study aimed to assess the completeness and correctness of MM registration using 3 independent national databases: the Belgian Cancer Registry (BCR), the population-based mortality statistics (certificates of death, COD), and the Belgian Mesothelioma Registry (BMR).

METHODS: The study cohort included all MM reported to the BCR and diagnosed between 2004 and 2012 (n = 2292), all patients reviewed by the pathology commission of the BMR (2004-2012; n = 2019), and COD data for all Belgian citizens (2004-2013). Available data were compared in terms of registered cases, histological diagnosis, performed immunohistochemical (IHC) tests, and IHC test results.

RESULTS: Comparison of BCR with BMR registrations showed 94.8% concordant cases. The proportion of MM diagnoses originally reported to BCR with unspecified MM morphology was reduced from 25.8% to less than 1%.

RESULTS: from IHC tests were available for 95.3% of concordant MM cases. Different IHC patterns could be distinguished by MM histology. MM cases registered at BCR for which COD mentioned an MM as underlying cause of death represented 76.4% of deceased cases. MM long-term survivors (survival >3 years; 10.9%) were characterised by distinct clinical and biological characteristics.

CONCLUSIONS: A comparison of independent Belgian MM registration databases elucidated under-registration and misclassification and revealed possible reasons for observed discordances. Combining all the available information resulted in enhanced completeness and correctness of MM registration in Belgium and allowed for the identification and characterisation of MM long-term survivors.}, } @article {pmid30030099, year = {2018}, author = {Sonvico, F and Barbieri, S and Colombo, P and Barocelli, E and Mucchino, C and Cantoni, AM and Petronini, PG and Rusca, M and Carbognani, P and Ampollini, L}, title = {Combined hyaluronate-based films loaded with pemetrexed and cisplatin for the treatment of malignant pleural mesothelioma: Preliminary evaluation in an orthotopic tumor recurrence model.}, journal = {European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences}, volume = {123}, number = {}, pages = {89-97}, doi = {10.1016/j.ejps.2018.07.035}, pmid = {30030099}, issn = {1879-0720}, mesh = {Animals ; *Antineoplastic Agents/administration & dosage/therapeutic use ; Cell Line, Tumor ; *Cisplatin/administration & dosage/therapeutic use ; *Drug Carriers ; *Hyaluronic Acid ; Lung Neoplasms/*drug therapy ; Male ; Mesothelioma/*drug therapy ; Mesothelioma, Malignant ; Neoplasm Recurrence, Local/drug therapy ; *Pemetrexed/administration & dosage/therapeutic use ; Pleural Neoplasms/*drug therapy ; Rats ; Rats, Inbred F344 ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare malignancy characterized by a long latency period of 20-50 years after exposure to the main aetiology agent that is asbestos. MPM treatments include surgery, chemotherapy, and radiation therapy, with the combination pemetrexed and cisplatin being the standard chemotherapy approach. Despite this multimodality therapy one of the major issues after surgery is the high rate of local recurrence of the tumor. One possible approach would be the intrapleural application of implants loaded with anticancer drug to be applied during surgery to prevent local tumor recurrence. The implant proposed in the present work is a polymeric film of hyaluronic acid loaded with pemetrexed. The film developed is a hydrophilic, thin and flexible film sufficiently resistant to be applied intrapleurally adhering to the mesothelial surface. The release of pemetrexed from the film was found to be complete within2 h in phosphate buffered saline. In an orthotopic model of mesothelioma recurrence in rats, pemetrexed loaded films showed the same antitumor efficacy of pemetrexed disodium solutions administered intravenously or intrapleurally, while when administered in combination with cisplatin-loaded hyaluronate film, the implants almost completely prevented tumor recurrence. The local administration of drug-loaded polymer implants appears an ideal chemotherapy strategy especially for patients in which surgery is already selected as a viable therapeutic option.}, } @article {pmid30030095, year = {2018}, author = {Mossman, BT}, title = {Mechanistic in vitro studies: What they have told us about carcinogenic properties of elongated mineral particles (EMPs).}, journal = {Toxicology and applied pharmacology}, volume = {361}, number = {}, pages = {62-67}, doi = {10.1016/j.taap.2018.07.018}, pmid = {30030095}, issn = {1096-0333}, mesh = {Air Pollutants, Occupational/*toxicity ; Animals ; Asbestos/toxicity ; Carcinogenesis ; Carcinogens/*toxicity ; Cell Transformation, Neoplastic/drug effects ; Chromosomes/drug effects ; DNA/drug effects ; Humans ; Minerals/*toxicity ; }, abstract = {In vitro studies using target and effecter cells of mineral-induced cancers have been critical in determining the mechanisms of pathogenesis as well as the properties of elongated mineral particles (EMPs) important in eliciting these responses. Historically, in vitro models of 'mutagenesis' and immortalized cell lines were first used to test the theory that EMPs were mutagenic to cells, and 'genotoxicity', as defined as damage to DNA often culminating in cell death, was observed in a dose-dependent fashion as responses of many cell types to a number of EMPs. As two-stage and multi-step models of cancer development emerged in the 1970s and 1980s, differentiated 3D organ cultures and monolayers of lung epithelial and mesothelial cells were used to probe the mechanisms of cancer development. These studies demonstrated a spectrum of pre-neoplastic changes, including hyperplasia and squamous metaplasia, in response to long (>5 μm in length) needlelike EMPs whereas long, curly chrysotile fibers caused acute cytotoxicity. Shorter fibers of many types were taken up by cells and encompassed in phagolysosomes. Comparative studies using chemical carcinogens showed that chemical agents interacted directly with DNA whereas long EMPs appeared to be promoters of cancers via a number of mechanisms such as inflammation, generation of oxidants, and instigation of cell division. The multitude of these signaling cascades and epigenetic mechanisms of both lung cancers and mesotheliomas have been most recently studied in normal or telomerase immortalized human cells. Importantly, many of these pathways are elicited by long, straight amphibole asbestos fibers or carbon nanotubes in rodents and not by short (<5 μm) EMPs, fragments, or nonfibrous particles. However, the chemistry and surface properties of long fibers are also critical in cell responses to minerals.}, } @article {pmid30030093, year = {2018}, author = {Abello, A and Steinkeler, J and Das, AK}, title = {A Bilateral Metachronous Mesothelioma of the Tunica Vaginalis.}, journal = {Urology}, volume = {120}, number = {}, pages = {e1-e2}, doi = {10.1016/j.urology.2018.07.003}, pmid = {30030093}, issn = {1527-9995}, abstract = {This is a unique case of bilateral metachronous testicular mesothelioma of the tunica vaginalis. Testicular mesothelioma is a rare entity found in patients with or without asbestos occupational exposure. The tumor most commonly presents as a unilateral testicular mass. More rare presentations include bilateral synchronous or metachronous tumors. Treatment is with surgical resection and prognosis is not generally favorable. The benefits of adjuvant therapy with radiation or chemotherapy remain unknown and further studies are needed.}, } @article {pmid30025147, year = {2019}, author = {Panou, V and Vyberg, M and Meristoudis, C and Hansen, J and Bøgsted, M and Omland, Ø and Weinreich, UM and Røe, OD}, title = {Non-occupational exposure to asbestos is the main cause of malignant mesothelioma in women in North Jutland, Denmark.}, journal = {Scandinavian journal of work, environment & health}, volume = {45}, number = {1}, pages = {82-89}, doi = {10.5271/sjweh.3756}, pmid = {30025147}, issn = {1795-990X}, mesh = {Asbestos/*toxicity ; Carcinogens/*toxicity ; Denmark/epidemiology ; Environmental Exposure/*adverse effects ; Female ; Humans ; Incidence ; Lung Neoplasms/*epidemiology ; Mesothelioma/*epidemiology ; Mesothelioma, Malignant ; Registries ; Risk Assessment ; }, abstract = {Objectives Diffuse malignant mesothelioma (MM) is mainly caused by asbestos inhalation. The malignancy is rare among women and studies of the prevalence and causative role of non-occupational asbestos exposure among women with MM are scarce. This observational study aimed to elucidate the asbestos exposure patterns among women with MM. Methods All histological and cytological specimens from women diagnosed with MM between 1974-2015 at the Institute of Pathology, Aalborg University Hospital in Denmark, were re-evaluated. Occupational and habitation information were obtained from Danish registries and medical journals based on record linkage via the unique person ID. The number of MM cases in each parish in the region of North Jutland was determined and the incidence density in parishes was used to calculate the spatial relative risk (RR) of MM among women. Results Diagnosis of MM was confirmed in 91 women. Exposure types were classified as occupational (9%), domestic (10%), environmental (22%), combination of domestic and environmental (34%) and unknown (25%). Twenty continuous parishes formed a MM "hotspot" around the asbestos-consuming industries in the city of Aalborg. Of these, the maximum RR was found in a parish housing an asbestos factory [RR 10.5, 95% confidence interval (CI) 5.5-19.4, environmental exposure in particular RR 2.9, 95% CI 0.7-6.1]. Conclusion Non-occupational asbestos exposure is the main cause of MM and may account for up to 66% of MM cases among women in North Jutland, Denmark.}, } @article {pmid30022998, year = {2018}, author = {Nabavi, N and Wei, J and Lin, D and Collins, CC and Gout, PW and Wang, Y}, title = {Pre-clinical Models for Malignant Mesothelioma Research: From Chemical-Induced to Patient-Derived Cancer Xenografts.}, journal = {Frontiers in genetics}, volume = {9}, number = {}, pages = {232}, pmid = {30022998}, issn = {1664-8021}, abstract = {Malignant mesothelioma (MM) is a rare disease often associated with environmental exposure to asbestos and other erionite fibers. MM has a long latency period prior to manifestation and a poor prognosis. The survival post-diagnosis is often less than a year. Although use of asbestos has been banned in the United States and many European countries, asbestos is still being used and extracted in many developing countries. Occupational exposure to asbestos, mining, and migration are reasons that we expect to continue to see growing incidence of mesothelioma in the coming decades. Despite improvements in survival achieved with multimodal therapies and cytoreductive surgeries, less morbid, more effective interventions are needed. Thus, identifying prognostic and predictive biomarkers for MM, and developing novel agents for targeted therapy, are key unmet needs in mesothelioma research and treatment. In this review, we discuss the evolution of pre-clinical model systems developed to study MM and emphasize the remarkable capability of patient-derived xenograft (PDX) MM models in expediting the pre-clinical development of novel therapeutic approaches. PDX disease model systems retain major characteristics of original malignancies with high fidelity, including molecular, histopathological and functional heterogeneities, and as such play major roles in translational research, drug development, and precision medicine.}, } @article {pmid30018519, year = {2018}, author = {Strbac, D and Goricar, K and Dolzan, V and Kovac, V}, title = {Matrix Metalloproteinases Polymorphisms as Baseline Risk Predictors in Malignant Pleural Mesothelioma.}, journal = {Radiology and oncology}, volume = {52}, number = {2}, pages = {160-166}, pmid = {30018519}, issn = {1318-2099}, abstract = {BACKGROUND: Malignant mesothelioma (MM) is a rare disease, linked to asbestos exposure in more than 80% of the cases. Matrix metalloproteinases (MMPs) have been identified as modulators of the tumour microenvironment and carcinogenesis. Polymorphisms of selected MMPs have been studied as potential biomarkers of time to progression (TTP) and overall survival (OS) in MM. The aim of our study was to investigate selected MMP polymorphisms as baseline risk predictors in MM development in combination with other well known risk factors, such as asbestos exposure.

PATIENTS AND METHODS: The study included 236 patients and 161 healthy blood donors as the control group. Ten different polymorphisms in three MMP genes were genotyped using a fluorescence-based competitive allele-specific assay (KASPar): MMP2 rs243865, rs243849 and rs7201, MMP9 rs17576, rs17577, rs2250889 and rs20544, and MMP14 rs1042703, rs1042704 and rs743257. In statistical analyses continuous variables were described using median and range (25%-75%), while frequencies were used to describe categorical variables. Deviation from the Hardy-Weinberg equilibrium (HWE) was assessed using the standard chi-square test. The additive and dominant genetic models were used in statistical analyses. The association of genetic polymorphism with MM risk were examined by logistic regression to calculate odds ratios (ORs) and their 95% confidence intervals (CIs).

RESULTS: Carriers of at least one polymorphic MMP2 rs243865 allele tended to have a decreased risk for MM (OR = 0.66, 95% CI = 0.44-1.00; P = 0.050). The association was more pronounced in patients with known asbestos exposure: carriers of at least one polymorphic allele had significantly lower MM risk (OR = 0.55, 95% CI = 0.35-0.86; P = 0.009). None of the other tested polymorphisms showed association with the risk of malignant pleural mesothelioma.

CONCLUSIONS: The MMP2 rs243865 polymorphism may have a protective role in malignant pleural mesothelioma development. This finding is even more evident in patients exposed to asbestos, implying a strong gene-environment interaction.}, } @article {pmid30009035, year = {2018}, author = {An, YS and Kim, HD and Kim, HC and Jeong, KS and Ahn, YS}, title = {The characteristics of asbestos-related disease claims made to the Korea Workers' Compensation and Welfare Service (KCOMWEL) from 2011 to 2015.}, journal = {Annals of occupational and environmental medicine}, volume = {30}, number = {}, pages = {45}, pmid = {30009035}, issn = {2052-4374}, abstract = {BACKGROUND: This study aimed to enhance understanding of the epidemiologic characteristics of asbestos-related diseases, and to provide information that could inform policy-making aimed at prevention and compensation for occupational asbestos exposure, through analyzing asbestos-related occupational disease claims to Korea Workers' Compensation and Welfare Service from 2011 to 2015.

METHODS: We analyzed 113 workers who filed medical care claims or survivor benefits for asbestos exposure and occupational-related disease from 2011 to 2015. Among these claims, we selected approved workers' compensation claims relating to malignant mesothelioma and lung cancer, and analyzed the general characteristics, exposure characteristics, pathological characteristics, and occupation and industry distribution.

RESULTS: Malignant mesothelioma and lung cancer occurred predominantly in males at 89.7 and 94%, respectively. The mean age at the time of diagnosis for malignant mesothelioma and lung cancer was 59.5 and 59.7 years, respectively, while the latency period for malignant mesothelioma and lung cancer was 34.1 and 33.1 years, respectively. The companies involving exposed workers were most commonly situated within the Busan-Ulsan-Gyeongnam region. Histology results for lung cancer indicated adenocarcinoma as the most common form, accounting for approximately one half of all claims, followed by squamous cell carcinoma, and small cell lung cancer. The most common occupation type was construction in respect of malignant mesothelioma, and shipbuilding in respect of lung cancer.

CONCLUSIONS: Considering the long latency period of asbestos and that the peak period of asbestos use in Korea was throughout the mid-1990s, damage due to asbestos-related diseases is expected to show a continued long-term increase. Few studies providing an epidemiologic analysis of asbestos-related diseases are available; therefore, this study may provide baseline data to assist in predicting and preparing for future harm due to asbestos exposure.

TRIAL REGISTRATION: DUIH 2018-02-004-001. Registered 28 Februrary 2018.}, } @article {pmid30008600, year = {2018}, author = {Aguilar-Madrid, G and Pesch, B and Calderón-Aranda, ES and Burek, K and Jiménez-Ramírez, C and Juárez-Pérez, CA and Ochoa-Vázquez, MD and Torre-Bouscoulet, L and Acosta-Saavedra, LC and Sada-Ovalle, I and García-Figueroa, J and Alvarado-Cabrero, I and Castillo-González, P and Báez-Saldaña, AR and Pérez-Padilla, JR and Osnaya-Juárez, J and Rivera-Rosales, RM and García-Bazán, EM and Bautista-Aragón, YL and Lazcano-Hernandez, E and Munguía-Canales, DA and Argote-Greene, LM and Taeger, D and Weber, DG and Casjens, S and Raiko, I and Brüning, T and Johnen, G}, title = {Biomarkers for Predicting Malignant Pleural Mesothelioma in a Mexican Population.}, journal = {International journal of medical sciences}, volume = {15}, number = {9}, pages = {883-891}, pmid = {30008600}, issn = {1449-1907}, mesh = {Aged ; Biomarkers, Tumor/*analysis ; Calbindin 2/*blood ; Case-Control Studies ; Female ; GPI-Linked Proteins/*blood ; Humans ; Lung Neoplasms ; Male ; Mesothelin ; Mesothelioma/blood/*diagnosis ; Mexico ; Middle Aged ; Pleural Neoplasms/blood/*diagnosis ; }, abstract = {Background: Diagnosis of malignant pleural mesothelioma (MPM) remains a challenge, especially when resources in pathology are limited. The study aimed to evaluate cost-effective tumor markers to predict the probability of MPM in plasma samples in order to accelerate the diagnostic workup of the tissue of potential cases. Methods: We conducted a case-control study stratified by gender, which included 75 incident cases with MPM from three Mexican hospitals and 240 controls frequency-matched by age and year of blood drawing. Plasma samples were obtained to determine mesothelin, calretinin, and thrombomodulin using enzyme-linked immunosorbent assays (ELISAs). We estimated the performance of the markers based on the area under the curve (AUC) and predicted the probability of an MPM diagnosis of a potential case based on the marker concentrations. Results: Mesothelin and calretinin, but not thrombomodulin were significant predictors of a diagnosis of MPM with AUCs of 0.90 (95% CI: 0.85-0.95), 0.88 (95% CI: 0.82-0.94), and 0.51 (95% CI: 0.41-0.61) in males, respectively. For MPM diagnosis in men we estimated a true positive rate of 0.79 and a false positive rate of 0.11 for mesothelin. The corresponding figures for calretinin were 0.81 and 0.18, and for both markers combined 0.84 and 0.11, respectively. Conclusions: We developed prediction models based on plasma concentrations of mesothelin and calretinin to estimate the probability of an MPM diagnosis. Both markers showed a good performance and could be used to accelerate the diagnostic workup of tissue samples in Mexico.}, } @article {pmid30001711, year = {2018}, author = {Kittaneh, M and Berkelhammer, C}, title = {Detecting germline BAP1 mutations in patients with peritoneal mesothelioma: benefits to patient and family members.}, journal = {Journal of translational medicine}, volume = {16}, number = {1}, pages = {194}, pmid = {30001711}, issn = {1479-5876}, mesh = {Female ; Germ-Line Mutation/*genetics ; Humans ; Laparoscopy ; Lung Neoplasms/diagnostic imaging/*genetics/pathology ; Male ; Mesothelioma/diagnostic imaging/*genetics/pathology ; Mesothelioma, Malignant ; Middle Aged ; Pedigree ; Peritoneal Neoplasms/diagnostic imaging/*genetics/pathology ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {Germline mutations in the BRCA-1 associated tumor protein 1 (BAP1) increase susceptibility to mesothelioma and other cancers. We describe a patient with a family history of peritoneal mesothelioma, who developed malignant peritoneal mesothelioma at age 45 in the absence of known asbestos exposure. These findings lead us to hypothesize that the mesothelioma occurred in the setting of germline a BAP1 mutation. This was confirmed by genetic testing. The subsequent therapeutic choices for the patient and testing of at-risk family members highlight the importance of recognizing this genetic syndrome and screening for individuals at high risk.}, } @article {pmid29990795, year = {2018}, author = {Fazzo, L and Minelli, G and De Santis, M and Bruno, C and Zona, A and Conti, S and Comba, P}, title = {Epidemiological surveillance of mesothelioma mortality in Italy.}, journal = {Cancer epidemiology}, volume = {55}, number = {}, pages = {184-191}, doi = {10.1016/j.canep.2018.06.010}, pmid = {29990795}, issn = {1877-783X}, mesh = {Female ; Humans ; Italy/epidemiology ; Lung Neoplasms/*epidemiology/*mortality ; Male ; Mesothelioma/*epidemiology/*mortality ; Mesothelioma, Malignant ; Pleural Neoplasms/*epidemiology/*mortality ; *Population Surveillance ; Prognosis ; Survival Rate ; }, abstract = {BACKGROUND: Malignant mesothelioma (MM) is causally linked to asbestos exposure with an estimated etiological fraction of 80% or more.

METHODS: Standardized rates of all mesothelioma (C45, ICD-10) and malignant pleural mesothelioma (C45.0, ICD-10) mortality in Italy were computed at national and regional levels, for the period 2003-2014. Standardized Mortality Ratios (SMRs, with 95% Confidence Intervals) were calculated for each of the 8047 Italian municipalities, for both diseases, with respect to Regional figures. A geographical clustering analysis at municipal level was performed, applying SatScan methods.

RESULTS: In Italy, 16,086 persons (about 1,340/year) died for MM, in analysed period. National Standardized rates of MM mortality are 3.65/100,000 in men and 1.09/100,000 in women, with an increasing annual trend, among male population. The highest rates were found in men from Northern Regions. Significant clusters (p < 0.10) were found corresponding to areas that hosted major asbestos-cement plants, naval shipyards, petrochemical plants and refineries. Furthermore, excesses were found corresponding to chemical and textile industries; the latter involving, particularly, female population. Excesses were found also in areas near the chrysotile mine of Balangero, and in Biancavilla, a town with a stone quarry contaminated by fluoro-edenitic fibres; an excess of MM mortality was observed among male population living in a minor island where a Navy shipyard is located.

CONCLUSIONS: Mortality for mesothelioma in Italy is still increasing, twenty-six years after the asbestos ban. Epidemiological surveillance of mesothelioma mortality allows to detect the temporal trend of the disease and highlights previously unknown or underestimated sources of asbestos exposure.}, } @article {pmid29982378, year = {2018}, author = {Dragani, TA and Colombo, F and Pavlisko, EN and Roggli, VL}, title = {Malignant mesothelioma diagnosed at a younger age is associated with heavier asbestos exposure.}, journal = {Carcinogenesis}, volume = {39}, number = {9}, pages = {1151-1156}, doi = {10.1093/carcin/bgy089}, pmid = {29982378}, issn = {1460-2180}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Asbestos/*analysis/*toxicity ; Environmental Exposure/*adverse effects ; Female ; Humans ; Lung Neoplasms/*chemically induced/*diagnosis ; Male ; Mesothelioma/*chemically induced/*diagnosis ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/*adverse effects ; }, abstract = {Asbestos exposure is the main etiology of malignant mesothelioma, but there are conflicting data on whether the intensity of exposure modulates the development of this disease. This study considered 594 patients with malignant mesothelioma for whom count data on asbestos bodies and fibers (per gram of wet lung tissue) were available. The relationships between age at diagnosis (a time-to-event outcome variable) and these two measures of internal asbestos exposure, along with other possible modulating factors (sex, tumor location, histological subtype and childhood exposure), were assessed on multivariable Cox proportional hazard models, stratifying by decade of birth year. For both measures of asbestos in lung tissue, younger age at diagnosis was associated with higher internal measures of exposure to asbestos. Stratified Cox analyses showed that for each doubling in asbestos body count patients were 1.07 times more likely to be diagnosed at a younger age [hazard ratio (HR) = 1.07; 95% confidence interval (CI), 1.04-1.09; P = 2.2 × 10-7] and for each doubling in asbestos fiber count patients were 1.13 times more likely to be diagnosed at a younger age (HR = 1.13; 95% CI, 1.09-1.17; P = 8.6 × 10-11). None of the other variables considered were associated with age at diagnosis. Our finding that tumors become clinically apparent at a younger age in heavily exposed subjects suggests that asbestos is involved not only in the malignant mesothelioma tumor initiation but, somehow, also in the progression of the disease.}, } @article {pmid29977434, year = {2018}, author = {Pranay, P and Serafimov, V and Hall, J and Goel, A and Mushtaq, M}, title = {Metastatic biphasic pleural mesothelioma presenting with cauda equina syndrome.}, journal = {Radiology case reports}, volume = {13}, number = {3}, pages = {736-739}, pmid = {29977434}, issn = {1930-0433}, abstract = {Patient with previous asbestos exposure on a watchful wait and watch regime presents acutely with cauda equina syndrome. Radiological imaging confirmed a mass with direct invasion of the spinal cord. Histology confirmed metastatic pleural mesothelioma.}, } @article {pmid29970876, year = {2018}, author = {Jones, RG and Karthik, F and Dugar, A and Kanagarajan, K and Desai, K and Bhandari, M}, title = {Nivolumab Immunotherapy in Malignant Mesothelioma: A Case Report Highlighting a New Opportunity for Exceptional Outcomes.}, journal = {The American journal of case reports}, volume = {19}, number = {}, pages = {783-789}, pmid = {29970876}, issn = {1941-5923}, mesh = {Aged ; Antibodies, Monoclonal/*therapeutic use ; Antineoplastic Agents/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Humans ; Immunotherapy ; Male ; Mesothelioma/*drug therapy ; Nivolumab ; Pleural Neoplasms/*drug therapy ; Treatment Outcome ; }, abstract = {BACKGROUND Malignant pleural mesothelioma (MPM) is a highly lethal cancer with a median survival of ~12 months even with aggressive intervention. Frontline therapy relies on systemic cisplatin and pemetrexed chemotherapy and has a response rate of ~35-41%; currently, there are no US Food and Drug Administration approved second-line therapies for MPM. Herein, we present a patient with MPM who experienced rapid disease progression after standard therapy but who had an exceptional and sustained response to immune checkpoint inhibition with single agent nivolumab. CASE REPORT A 68-year-old male with a history of work-related asbestos exposure was diagnosed with MPM. He was treated with primary resection followed by systemic chemotherapy with cisplatin and pemetrexed. When chemotherapy failed, he was switched to immunotherapy with nivolumab and achieved an exceptional response. CONCLUSIONS We report the first case of a patient with MPM who experienced rapid disease progression after standard therapy but had an exceptional and sustained response to immune checkpoint inhibition with single agent nivolumab. As outcomes with traditional chemotherapy regimens remain disappointing, there is a substantial need for new approaches to MPM; our case highlights a new therapeutic opportunity even in the face of aggressive disease. Indeed, a new era of investigation utilizing immunotherapy for mesothelioma is beginning, with much anticipation.}, } @article {pmid29966799, year = {2018}, author = {Mutti, L and Peikert, T and Robinson, BWS and Scherpereel, A and Tsao, AS and de Perrot, M and Woodard, GA and Jablons, DM and Wiens, J and Hirsch, FR and Yang, H and Carbone, M and Thomas, A and Hassan, R}, title = {Scientific Advances and New Frontiers in Mesothelioma Therapeutics.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {13}, number = {9}, pages = {1269-1283}, pmid = {29966799}, issn = {1556-1380}, support = {Z01 BC010816-01//Intramural NIH HHS/United States ; }, mesh = {Humans ; *Lung Neoplasms ; *Mesothelioma ; Mesothelioma, Malignant ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer that arises from the mesothelial surface of the pleural and peritoneal cavities, the pericardium, and rarely, the tunica vaginalis. The incidence of MPM is expected to increase worldwide in the next two decades. However, even with the use of multimodality treatment, MPM remains challenging to treat, with a 5-year survival rate of less than 5%. The International Association for the Study of Lung Cancer has gathered experts in different areas of mesothelioma research and management to summarize the most significant scientific advances and new frontiers related to mesothelioma therapeutics.}, } @article {pmid29961174, year = {2018}, author = {Hylebos, M and Op de Beeck, K and van den Ende, J and Pauwels, P and Lammens, M and van Meerbeeck, JP and Van Camp, G}, title = {Molecular analysis of an asbestos-exposed Belgian family with a high prevalence of mesothelioma.}, journal = {Familial cancer}, volume = {17}, number = {4}, pages = {569-576}, pmid = {29961174}, issn = {1573-7292}, mesh = {Asbestos/*toxicity ; Belgium ; Female ; Humans ; Lung Neoplasms/chemically induced/epidemiology/*genetics ; Male ; Mesothelioma/chemically induced/epidemiology/*genetics ; Mesothelioma, Malignant ; Middle Aged ; Mutation ; Prevalence ; RNA-Binding Proteins/genetics ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {Familial clustering of malignant mesothelioma (MM) has been linked to the presence of germline mutations in BAP1. However, families with multiple MM patients, without segregating BAP1 mutation were described, suggesting the existence of other predisposing genetic factors. In this study, we report a previously undescribed Belgian family, in which BAP1 was found to be absent in the epithelial malignant mesothelial cells of the index patient. Whole exome analysis did not reveal a germline or somatic BAP1 variant. Also, no germline or somatic copy number changes in the BAP1 region could be identified. However, germline variants, predicted to be damaging, were detected in 11 other 'Cancer census genes' (i.e. MPL, RBM15, TET2, FAT1, HLA-A, EGFR, KMT2C, BRD3, NOTCH1, RB1 and MYO5A). Of these, the one in RBM15 seems to be the most interesting given its low minor allele frequency and absence in the germline DNA of the index patient's mother. The importance of this 'Cancer census gene' in familial MM clustering needs to be evaluated further. Nevertheless, this study strengthens the suspicion that, next to germline BAP1 alterations, other genetic factors might predispose families to the development of MM.}, } @article {pmid29960000, year = {2018}, author = {Kane, AB and Hurt, RH and Gao, H}, title = {The asbestos-carbon nanotube analogy: An update.}, journal = {Toxicology and applied pharmacology}, volume = {361}, number = {}, pages = {68-80}, pmid = {29960000}, issn = {1096-0333}, support = {P42 ES013660/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Asbestos/*toxicity ; Carcinogens/*toxicity ; Disease Models, Animal ; Humans ; Lung Diseases/chemically induced ; Nanostructures/toxicity ; Nanotechnology ; Nanotubes, Carbon/*toxicity ; Occupational Exposure/adverse effects ; }, abstract = {Nanotechnology is an emerging industry based on commercialization of materials with one or more dimensions of 100 nm or less. Engineered nanomaterials are currently incorporated into thin films, porous materials, liquid suspensions, or filler/matrix nanocomposites with future applications predicted in energy and catalysis, microelectronics, environmental sensing and remediation, and nanomedicine. Carbon nanotubes are one-dimensional fibrous nanomaterials that physically resemble asbestos fibers. Toxicologic studies in rodents demonstrated that some types of carbon nanotubes can induce mesothelioma, and the World Health Organization evaluated long, rigid multiwall carbon nanotubes as possibly carcinogenic for humans in 2014. This review summarizes key physicochemical similarities and differences between asbestos fibers and carbon nanotubes. The "fiber pathogenicity paradigm" has been extended to include carbon nanotubes as well as other high-aspect-ratio fibrous nanomaterials including metallic nanowires. This paradigm identifies width, length, and biopersistence of high-aspect-ratio fibrous nanomaterials as critical determinants of lung disease, including mesothelioma, following inhalation. Based on recent theoretical modeling studies, a fourth factor, mechanical bending stiffness, will be considered as predictive of potential carcinogenicity. Novel three-dimensional lung tissue platforms provide an opportunity for in vitro screening of a wide range of high aspect ratio fibrous nanomaterials for potential lung toxicity prior to commercialization.}, } @article {pmid29959999, year = {2018}, author = {Roggli, VL}, title = {Measuring EMPs in the lung what can be measured in the lung: Asbestiform minerals and cleavage fragments.}, journal = {Toxicology and applied pharmacology}, volume = {361}, number = {}, pages = {14-17}, doi = {10.1016/j.taap.2018.06.026}, pmid = {29959999}, issn = {1096-0333}, mesh = {Air Pollutants, Occupational ; Asbestos/*analysis ; Humans ; Lung/*chemistry ; Lung Neoplasms ; Mesothelioma ; Mesothelioma, Malignant ; Microscopy, Electron, Scanning ; Microscopy, Electron, Transmission ; Mineral Fibers/analysis ; Minerals/*analysis ; Particle Size ; Particulate Matter/*analysis ; }, abstract = {Asbestos mineral fibers have been associated with the development of a variety of diseases in humans and experimental animals, including asbestosis, lung cancer, and mesothelioma. Asbestos includes several mineral types divided into two mineral groups, serpentine and amphibole forms. Chrysotile is the serpentine mineral classified as asbestos, whereas the amphiboles include amosite, crocidolite, tremolite, actinolite and anthophyllite. There are a number of mineral fibers that occur with asbestiform morphology and that have been associated with various asbestos-induced diseases. These include the Libby amphiboles (associated with a vermiculite mine northwest of Libby, MT), erionite (in Turkey and North America), fluoro-edenite (in Sicily), and perhaps balangeroite (in Italy). In addition, each of the asbestos minerals occurs in a non-fibrous form, and these may occur as cleavage fragments that satisfy the definition for a fiber, i.e., particles with an aspect ratio of at least 3:1 and roughly parallel sides. Cleavage fragments of non-asbestiform minerals have not been associated with asbestos-induced diseases nor are these minerals regulated by the Occupational Safety and Health Administration. Finally, there are a number of other mineral species which can occur in human lung samples that satisfy the definition for a fiber as given above. These similarly have not been associated with asbestos-induced diseases. All of these various minerals satisfying the definition for a fiber can be referred to as elongated mineral particles (EMP). It is the purpose of this presentation to discuss the role of scanning electron microscopy (SEM) equipped with an energy dispersive x-ray analyzer (EDXA) in the detection and classification of EMP in human lung samples.}, } @article {pmid29949929, year = {2018}, author = {Colin, DJ and Cottet-Dumoulin, D and Faivre, A and Germain, S and Triponez, F and Serre-Beinier, V}, title = {Experimental Model of Human Malignant Mesothelioma in Athymic Mice.}, journal = {International journal of molecular sciences}, volume = {19}, number = {7}, pages = {}, pmid = {29949929}, issn = {1422-0067}, mesh = {Animals ; Body Fluids/metabolism ; Carcinogenesis/pathology ; Cell Count ; Cell Line, Tumor ; Cell Survival ; Epithelial-Mesenchymal Transition/genetics ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/genetics/immunology/*pathology ; Macrophages/metabolism ; Mesothelioma/genetics/immunology/*pathology ; Mesothelioma, Malignant ; Mice, Nude ; *Xenograft Model Antitumor Assays ; }, abstract = {Malignant pleural mesothelioma (MPM) is a thoracic aggressive cancer caused by asbestos exposure, which is difficult to diagnose and treat. Here, we characterized an in vivo orthotopic xenograft model consisting of human mesothelioma cells (designed as H2052/484) derived from a pleural NCI-H2052 tumor injected in partially immunodeficient athymic mice. We assessed tumor formation and tumor-dependent patterns of inflammation. H2052/484 cells conserved their mesothelioma phenotype and most characteristics from the parental NCI-H2052 cells. After intra-thoracic injection of H2052/484 cells, thoracic tumors developed in nearly all mice (86%) within 14 days, faster than from parental NCI-H2052 cells. When the mice were euthanized, the pleural lavage fluid was examined for immune cell profiles. The pleural immune cell population increased with tumor development. Interestingly, the proportion of myeloid-derived suppressor cell and macrophage (especially CD206[+] M2 macrophages) populations increased in the pleural fluid of mice with large mesothelioma development, as previously observed in immunocompetent mice. This reliable orthotopic model recapitulates human mesothelioma and may be used for the study of new treatment strategies.}, } @article {pmid29946373, year = {2018}, author = {Bensaid, D and Blondy, T and Deshayes, S and Dehame, V and Bertrand, P and Grégoire, M and Errami, M and Blanquart, C}, title = {Assessment of new HDAC inhibitors for immunotherapy of malignant pleural mesothelioma.}, journal = {Clinical epigenetics}, volume = {10}, number = {}, pages = {79}, pmid = {29946373}, issn = {1868-7083}, mesh = {B7-H1 Antigen/*genetics/metabolism ; Benzamides/pharmacology/therapeutic use ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; DNA Methylation/drug effects ; Decitabine/*pharmacology/therapeutic use ; Dose-Response Relationship, Drug ; Drug Therapy, Combination ; Epigenesis, Genetic/drug effects ; Gene Expression Regulation, Neoplastic/drug effects ; Histone Deacetylase Inhibitors/*pharmacology/therapeutic use ; Humans ; Hydroxamic Acids/pharmacology/therapeutic use ; Immunotherapy ; Killer Cells, Natural/cytology/drug effects ; Lung Neoplasms/drug therapy/*genetics/metabolism ; Male ; Mesothelioma/drug therapy/*genetics/metabolism ; Mesothelioma, Malignant ; T-Lymphocytes, Regulatory/cytology/drug effects ; Valproic Acid/*pharmacology/therapeutic use ; Vorinostat/*pharmacology/therapeutic use ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a very rare and highly aggressive cancer of the pleura associated in most cases with asbestos exposure. To date, no really efficient treatments are available for this pathology. Recently, it has been shown that epigenetic drugs, particularly DNA methylation or histone acetylation modulating agents, could be very efficient in terms of cytotoxicity for several types of cancer cells. We previously showed that a hypomethylating agent (decitabine) and a histone deacetylase inhibitor (HDACi) (valproic acid (VPA)) combination was immunogenic and led to the induction of an anti-tumor immune response in a mice model of mesothelioma. However, VPA is not very specific, is active at millimolar concentrations and is responsible for side effects in clinic. To improve this approach, we studied four newly synthetized HDACi, two hydroxamates (ODH and NODH) and two benzamides (ODB and NODB), in comparison with VPA and SAHA. We evaluated their toxicity on immune cells and their immunogenicity on MPM cells in combination with decitabine.

RESULTS: All the tested HDACi were toxic for immune cells at high concentrations. Combination with decitabine increased toxicity of HDACi only towards T-cell clone. A decrease in the proportion of regulatory T cells and natural killer cells was observed in particular with VPA and ODH. In MPM cells, all HDACi combinations induced NY-ESO-1 cancer testis antigen (CTA) expression and the recognition of the treated cells by a NY-ESO-1 specific T-CD8 clone. However, for MAGE-A1, MAGE-A3 and XAGE-1b mRNA expression, the results obtained depended on the HDACi used and on the CTA studied. Depending on the MPM cell line studied, molecules alone increased moderately PD-L1 expression. When combined, a higher stimulation of this immune check point inhibitor expression was observed. Decitabine-induced anti-viral response seemed to be inhibited in the presence of HDACi.

CONCLUSIONS: This work shows that the combination of decitabine and HDACi could be of interest for MPM immunotherapy. However, this combination induced PD-L1 expression which suggests that an association with anti-PD-L1 therapy should be performed to induce an efficient anti-tumor immune response.}, } @article {pmid29932955, year = {2018}, author = {Cox, LAT}, title = {Biological mechanisms of non-linear dose-response for respirable mineral fibers.}, journal = {Toxicology and applied pharmacology}, volume = {361}, number = {}, pages = {137-144}, doi = {10.1016/j.taap.2018.06.016}, pmid = {29932955}, issn = {1096-0333}, mesh = {Animals ; Cytokines ; Dose-Response Relationship, Drug ; Humans ; Inflammasomes/*drug effects ; Inhalation Exposure/*adverse effects ; Mineral Fibers/*toxicity ; NLR Family, Pyrin Domain-Containing 3 Protein/*genetics ; Particulate Matter/*toxicity ; Risk Assessment ; }, abstract = {Sufficiently high and prolonged inhalation exposures to some respirable elongated mineral particles (REMPs), notably including amphibole asbestos fibers, can increase risk of inflammation-mediated diseases including malignant mesothelioma, pleural diseases, fibrosis, and lung cancer. Chronic inflammation involves ongoing activation of the NLRP3 inflammasome, which enables immune cells to produce potent proinflammatory cytokines IL-1β and IL-18. Reactive oxygen species (ROS) (in particular, mitochondrial ROS) contribute to NRLP3 activation via a well-elucidated mechanism involving oxidation of reduced thioredoxin and association of thioredoxin-interacting protein with NLRP3. Lysosomal destabilization, efflux of cytosolic potassium ions and influx of calcium ions, signals from damaged mitochondria, both translational and post-translational controls, and prion-like polymerization have increasingly clear roles in regulating NLRP3 activation. As the molecular biology of inflammation-mediated responses to REMP exposure becomes clearer, a practical question looms: What do these mechanisms imply for the shape of the dose-response function relating exposure concentrations and durations for EMPs to risk of pathological responses? Dose-response thresholds or threshold-like nonlinearities can arise from (a) Cooperativity in assembly of supramolecular signaling complexes; (b) Positive feedback loops and bistability in regulatory networks; (c) Overwhelming of defensive barriers maintaining homeostasis; and (d) Damage thresholds, as in lysosome destabilization-induced activation of NLRP3. Each of these mechanisms holds for NLRP3 activation in response to stimuli such as REMP exposures. It is therefore timely to consider the implications of these advances in biological understanding for human health risk assessment with dose-response thresholds.}, } @article {pmid29928505, year = {2018}, author = {Blum, W and Henzi, T and Châtel-Soulet, HE and Pecze, L and Rodriguez, JW and Vrugt, B and Schwaller, B}, title = {Absence of calretinin protein expression in malignant mesotheliomas from asbestos-exposed NF2[+/-] mice and mouse mesothelioma cell lines from various mouse strains.}, journal = {Biomarker research}, volume = {6}, number = {}, pages = {19}, pmid = {29928505}, issn = {2050-7771}, abstract = {BACKGROUND: Calretinin is the most widespread positive marker for the immunohistochemical identification of malignant mesothelioma (MM) and was proposed to serve as a blood-based biomarker. Functionally, evidence has accumulated that calretinin might be implicated in MM tumorigenesis. We aimed to identify calretinin (CR; Calb2) in murine MM and reactive mesothelial cells in granuloma from asbestos-exposed NF2[+/-] mice, a line heterozygous for the tumor suppressor merlin (NF2), used as a mouse MM model. Additionally, we sought to ascertain the presence of calretinin in MM cell lines from other mouse strains. We also intended to investigate the role of calretinin in mesotheliomagenesis by comparing the survival of asbestos-exposed NF2[+/-] and NF2[+/-]CR[-/-] mice.

METHODS: NF2[+/-] and NF2[+/-]CR[-/-] mice, both lines on a C57Bl/6J background, were exposed to asbestos following an established protocol. Tumor histology and asbestos-induced mortality were assessed. MM and granuloma from NF2[+/-] mice were analyzed with immunohistochemical methods for calretinin expression. Levels of Calb2 mRNA and calretinin expression in tumors and MM cell lines of various mouse strains were determined by RT-qPCR and Western blot analysis, respectively.

RESULTS: No expression of calretinin at the protein level was detected, neither in MM from NF2[+/-] mice, NF2[+/-] MM-derived cell lines nor immortalized mesothelial cells of mouse origin. At the mRNA level we detected Calb2 expression in MM cell lines from different mouse strains. Survival of NF2[+/-] and NF2[+/-]CR[-/-] mice exposed to asbestos showed no significant difference in a log-rank (Kaplan-Meier) comparison.

CONCLUSIONS: The concomitant determination of calretinin and mesothelin blood levels has been proposed for early detection of human MM. Mouse MM models based on asbestos exposure are assumed to yield helpful information on the time course of appearance of mesothelin and calretinin in the blood of asbestos-treated mice determining the earliest time point for interventions. However, the observed absence of calretinin in MM from NF2[+/-] mice and derived cell lines, as well as from MM cells from Balb/c and C3H mice likely precludes the use of calretinin as a biomarker for mouse MM. The results also indicate possible species differences with respect to an involvement of calretinin in the formation of MM.}, } @article {pmid29916421, year = {2018}, author = {Granieri, A and Borgogno, FV and Franzoi, IG and Gonella, M and Guglielmucci, F}, title = {Development of a Brief Psychoanalytic Group therapy (BPG) and its application in an asbestos national priority contaminated site.}, journal = {Annali dell'Istituto superiore di sanita}, volume = {54}, number = {2}, pages = {160-166}, doi = {10.4415/ANN_18_02_12}, pmid = {29916421}, issn = {2384-8553}, mesh = {Asbestos/*adverse effects ; Environmental Exposure ; Humans ; Lung Neoplasms/*psychology ; Mesothelioma/*psychology ; Mesothelioma, Malignant ; Occupational Exposure ; Psychoanalytic Therapy/*methods ; Psychotherapy, Group/*methods ; }, abstract = {The aim of the present paper is to describe the development of a Brief Psychoanalytic Group therapy for contaminated sites and its application in the National Priority Contaminated Site of Casale Monferrato. Before presenting the core of the clinical intervention, a brief examination of some clinical features encountered working with malignant mesothelioma patients and their caregivers is offered. These aspects have been pivotal elements in the construction of a psychoanalytically oriented time-limited (i.e., 12 sessions) group therapy. This model of intervention was designed by one of the Authors (AG) and is aimed at reducing the impact of living in a threatening place where both physical well-being and health are put to the test. At a psychological level, in fact, living in contaminated sites arouses death anxieties, which can deeply compromise the quality of time remaining to live together with loved ones after a fatal cancer diagnosis.}, } @article {pmid29916419, year = {2018}, author = {Comba, P and D'Angelo, M and Fazzo, L and Magnani, C and Marinaccio, A and Mirabelli, D and Terracini, B}, title = {Mesothelioma in Italy: the Casale Monferrato model to a national epidemiological surveillance system.}, journal = {Annali dell'Istituto superiore di sanita}, volume = {54}, number = {2}, pages = {139-148}, doi = {10.4415/ANN_18_02_10}, pmid = {29916419}, issn = {2384-8553}, mesh = {Case-Control Studies ; Cohort Studies ; Environmental Exposure ; Humans ; Incidence ; Italy/epidemiology ; Lung Neoplasms/epidemiology ; Mesothelioma/*epidemiology ; Mesothelioma, Malignant ; Occupational Diseases/epidemiology ; Occupational Exposure ; Pleural Neoplasms/epidemiology ; Population Surveillance ; }, abstract = {The purpose of the present paper is to review the origin and development of the epidemiology of mesothelioma in Italy, starting with the detection and investigation of the major outbreak of the disease observed in Casale Monferrato, Piedmont Region. Over the last four decades, mortality among the cohort of ex-Eternit workers has been measured at three points in time. More recently, population based case-control studies in the area of Casale Monferrato have provided new light on the dose-response curve of the relationship between asbestos exposure and mesotheliomas. The publication of the first Casale Monferrato study had a major impact in the country and contributed to the decision of the Italian Parliament to ban the use of asbestos. The experience of Casale Monferrato represents a lesson in several terms, from the epidemiological surveillance to the health care of the victims and the relationship between epidemiologists, victims, their relatives and residents in contaminated areas.}, } @article {pmid29915796, year = {2018}, author = {Losi, L and Botticelli, L and Taccagni, G and Longinotti, E and Lancellotti, C and Scurani, L and Zannoni, GF}, title = {Malignant peritoneal mesothelioma in a woman with bilateral ovarian serous borderline tumour: Potential interactions between the two diseases.}, journal = {Gynecologic oncology reports}, volume = {24}, number = {}, pages = {39-42}, pmid = {29915796}, issn = {2352-5789}, abstract = {We report a case of a 59-year-old woman with peritoneal malignant mesothelioma and no previous exposure to asbestos with a diagnosis of bilateral ovarian serous borderline tumour with peritoneal implants one year before. We discuss the histopathological and immunohistochemical findings to explain possible and potential interactions between the two diseases. To our knowledge, the association of both serous borderline ovarian tumour and malignant peritoneal mesothelioma has never been described before in the same woman and in such a tight temporal connection. This finding raises numerous issues about the origin of the two tumours and further biomolecular studies are needed to fully understand the carcinogenetic process. From a clinical point of view, this case report can be useful to gynaecologists because it leads to recommend a careful examination of the peritoneal cavity during a surgical resection of borderline serous tumour. Moreover, it may suggest performing a close follow-up associated with a careful surveillance of the patient, especially in the case of micropapillary pattern, to oncologists. A complete clinical approach could help to detect sooner possible relapses or other metachronous malignancies.}, } @article {pmid29914087, year = {2018}, author = {Ledda, C and Senia, P and Rapisarda, V}, title = {Biomarkers for Early Diagnosis and Prognosis of Malignant Pleural Mesothelioma: The Quest Goes on.}, journal = {Cancers}, volume = {10}, number = {6}, pages = {}, pmid = {29914087}, issn = {2072-6694}, abstract = {Malignant pleural mesothelioma (MM) is a highly aggressive tumor characterized by a poor prognosis. Although its carcinogenesis mechanism has not been strictly understood, about 80% of MM can be attributed to occupational and/or environmental exposure to asbestos fibers. The identification of non-invasive molecular markers for an early diagnosis of MM has been the subject of several studies aimed at diagnosing the disease at an early stage. The most studied biomarker is mesothelin, characterized by a good specificity, but it has low sensitivity, especially for non-epithelioid MM. Other protein markers are Fibulin-3 and osteopontin which have not, however, showed a superior diagnostic performance. Recently, interesting results have been reported for the HMGB1 protein in a small but limited series. An increase in channel proteins involved in water transport, aquaporins, have been identified as positive prognostic factors in MM, high levels of expression of aquaporins in tumor cells predict an increase in survival. MicroRNAs and protein panels are among the new indicators of interest. None of the markers available today are sufficiently reliable to be used in the surveillance of subjects exposed to asbestos or in the early detection of MM. Our aim is to give a detailed account of biomarkers available for MM.}, } @article {pmid29908246, year = {2018}, author = {Utell, MJ and Maxim, LD}, title = {Refractory ceramic fibers: Fiber characteristics, potential health effects and clinical observations.}, journal = {Toxicology and applied pharmacology}, volume = {361}, number = {}, pages = {113-117}, doi = {10.1016/j.taap.2018.06.011}, pmid = {29908246}, issn = {1096-0333}, mesh = {Air Pollutants, Occupational ; Ceramics/*toxicity ; Humans ; Inhalation Exposure ; Mineral Fibers/*toxicity ; Occupational Diseases ; Occupational Exposure ; Respiratory Tract Diseases/chemically induced/pathology ; }, abstract = {Refractory ceramic fibers (RCFs) are amorphous fibers that belong to a class of materials termed synthetic vitreous fibers (SVFs), also called man-made mineral fibers (MMMFs), which includes alkaline earth silicate wool, glass wool, rock (stone) wool, slag wool, and special-purpose glass fibers. RCFs are more durable and biopersistent than several other SVFs, although very much less biopersistent than either amosite or crocidolite asbestos. Chronic inhalation studies indicated that rats and hamsters exposed to RCF fibers developed fibrosis and tumors. Epidemiological studies at the University of Cincinnati funded by the Industry indicated that exposed workers; (1) exhibited symptoms (e.g., dyspnea) similar to those reported in other dust-exposed populations, (2) developed statistically, but not clinically, significant deficits in certain measures of pulmonary function in a cross sectional study, but no excessive decline in a longitudinal study, and (3) a dose related increase in pleural plaques, but no interstitial fibrosis. The 2003 mortality study indicated no incremental lung cancer and no cases of mesothelioma. RCF producers developed a comprehensive industry wide product stewardship program (PSP) beginning in the late 1980s. In conjunction with the PSP, there has been a progressive decrease in the TWA concentration of fibers by manufacturers and end-users. The research program has successfully produced more soluble fibers and undertaken efforts to develop larger diameter fibers. The results of the ongoing epidemiology studies confirm that occupational exposure to RCF is associated with the development of pleural plaques and minor decrements in lung function, but no interstitial fibrosis or incremental lung cancer.}, } @article {pmid29895204, year = {2018}, author = {Tweedale, G and Castleman, B}, title = {Jock McCulloch (1945-2018): A Tribute.}, journal = {International journal of health services : planning, administration, evaluation}, volume = {48}, number = {3}, pages = {586-591}, doi = {10.1177/0020731418780607}, pmid = {29895204}, issn = {1541-4469}, mesh = {Agent Orange/history/toxicity ; Asbestosis/history ; Australia ; History, 20th Century ; History, 21st Century ; Humans ; Occupational Diseases/history ; Occupational Health/*history ; South Africa ; }, abstract = {Jock William McCulloch, who died at Melbourne, Australia, in January 2018, was one of the foremost historians of occupational health of his generation. This tribute reviews his career and oeuvre, which was tragically ended by his death from mesothelioma.}, } @article {pmid29873855, year = {2018}, author = {Angelico, G and Ieni, A and Caltabiano, R and Zeppa, P and Tuccari, G}, title = {Aquaporin-1 expression in fluoro-edenite-induced mesothelioma effusions: An approach by cell-block procedure.}, journal = {Cytopathology : official journal of the British Society for Clinical Cytology}, volume = {29}, number = {5}, pages = {455-460}, doi = {10.1111/cyt.12583}, pmid = {29873855}, issn = {1365-2303}, mesh = {Aged ; Aged, 80 and over ; Aquaporin 1/*metabolism ; Asbestos, Amphibole/*toxicity ; Biomarkers, Tumor/*metabolism ; Cohort Studies ; Cytodiagnosis ; Female ; Humans ; Italy/epidemiology ; Lung Neoplasms/*chemically induced/*diagnosis/mortality ; Male ; Mesothelioma/*chemically induced/*diagnosis/mortality ; Mesothelioma, Malignant ; Middle Aged ; Pleural Effusion, Malignant/*chemically induced/*diagnosis/mortality ; Prognosis ; }, abstract = {OBJECTIVE: Aquaporin 1 (AQP-1) is a water channel protein found in cell membranes, whose expression has been considered an independent favourable prognostic factor in pleural malignant mesothelioma (MM). The aim of this study was to evaluate the expression of AQP-1 and its prognostic value in a series of pleural MM effusions, from a geographical area with high concentrations of fluoro-edenite (FE).

METHODS: We selected 25 MM cases from Biancavilla (Italy), an area with high environmental concentrations of FE. Cytological samples, cell-blocks (CB), clinical and follow-up data were available for all cases. Immunohistochemistry for calretinin, CK5/6, WT1, CK7 and TTF1 was used on CB sections to confirm the cytological diagnosis of MM. Immunohistochemistry for AQP-1 was performed and high expression was defined when ≥50% of tumour cells showed linear and circumferential membranous staining.

RESULTS: The cohort included 16 men and nine women (median age: 67.5 years; range: 49-88 years). The median survival was 14 months (range 1.5-60 months), with a significant value (P = 0.006). All cases have been histologically confirmed and classified as epithelioid (16 cases), biphasic (seven cases) and sarcomatoid (two cases). AQP-1 high expression has been observed in 16 cases. Comparing AQP-1 high expression to the survival of corresponding patients, a significant association with a slight increased overall survival of 12 months has been demonstrated. Nine patients with a AQP-1 score less than 50% showed a shorter median overall survival (7 months).

CONCLUSIONS: AQP-1 high expression is detectable on cytological samples of FE-induced MM with a prognostic value.}, } @article {pmid29869702, year = {2018}, author = {Barbiero, F and Zanin, T and Pisa, FE and Casetta, A and Rosolen, V and Giangreco, M and Negro, C and Bovenzi, M and Barbone, F}, title = {Cancer incidence in a cohort of asbestos-exposed workers undergoing health surveillance.}, journal = {International archives of occupational and environmental health}, volume = {91}, number = {7}, pages = {831-841}, pmid = {29869702}, issn = {1432-1246}, mesh = {Adult ; Aged ; Asbestos/*toxicity ; Cohort Studies ; Humans ; Incidence ; Italy/epidemiology ; Lung Neoplasms/*epidemiology/etiology ; Male ; Mesothelioma/*epidemiology/etiology ; Mesothelioma, Malignant ; Middle Aged ; Neoplasms/epidemiology/etiology ; Occupational Diseases/*epidemiology/etiology ; Occupational Exposure/*adverse effects ; Population Surveillance ; }, abstract = {OBJECTIVES: To compare a local cohort of 2488 men occupationally exposed to asbestos and enrolled in a public health surveillance program with the 1995-2009 cancer incidence of the general population of Friuli Venezia Giulia (FVG) region, Northeast Italy, we conducted a historical cohort study.

METHODS: Standardized incidence ratios (SIRs), with 95% confidence interval (95% CI), for specific cancer sites were estimated in the cohort and in subgroups of workers employed in shipbuilding between 1974 and 1994. For internal comparisons, we calculated incidence rate ratios (IRRs) for all cancers, lung cancer and mesothelioma, by level of exposure to asbestos and sector of employment adjusted for smoking habits and age at start of follow-up.

RESULTS: Among cohort members the SIR was 8.82 (95% CI 5.95-12.61) for mesothelioma and 1.61 (95% CI 1.26-2.04) for lung cancer. In subgroup analyses, the SIR for lung cancer in subjects hired in shipbuilding between 1974 and 1984 was 2.09 (95% CI 1.32-3.13). In the overall cohort, a borderline increased incidence was also found for stomach cancer (SIR = 1.53 95% CI 0.96-2.31). Internal comparisons within the cohort show that among men with high asbestos exposure level the relative risk was almost threefold for lung cancer (IRR = 2.94 95% CI 1.01-8.57).

CONCLUSIONS: This cohort experienced an excess in the incidence of both mesothelioma and lung cancer, showing increasing incidence rates at higher level of asbestos exposure. For lung cancer, the relative incidence was highest among workers hired in shipbuilding between 1974 and 1984.}, } @article {pmid29853412, year = {2018}, author = {Fujimoto, N and Aoe, K and Kozuki, T and Oze, I and Kato, K and Kishimoto, T and Hotta, K}, title = {A Phase II Trial of First-Line Combination Chemotherapy With Cisplatin, Pemetrexed, and Nivolumab for Unresectable Malignant Pleural Mesothelioma: A Study Protocol.}, journal = {Clinical lung cancer}, volume = {19}, number = {5}, pages = {e705-e707}, doi = {10.1016/j.cllc.2018.05.001}, pmid = {29853412}, issn = {1938-0690}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Cisplatin/administration & dosage ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/*drug therapy/pathology ; Male ; Mesothelioma/*drug therapy/pathology ; Mesothelioma, Malignant ; Middle Aged ; Nivolumab/administration & dosage ; Pemetrexed/administration & dosage ; Pleural Neoplasms/*drug therapy/pathology ; Prognosis ; Prospective Studies ; *Research Design ; Survival Rate ; Young Adult ; }, abstract = {BACKGROUND: The purpose of this study is to assess the efficacy and safety of combination chemotherapy with cisplatin, pemetrexed, and nivolumab for unresectable malignant pleural mesothelioma (MPM).

PATIENTS AND METHODS: Patients with untreated, advanced, or metastatic MPM who meet the inclusion and exclusion criteria will be included. A total of 18 patients will be enrolled from 4 Japanese institutions within 1 year. Combination chemotherapy with cisplatin (75 mg/m[2]), pemetrexed (500 mg/m[2]), and nivolumab (360 mg/person) is administered every 3 weeks for a total of 4 to 6 cycles. Then, maintenance therapy with nivolumab will be administered until disease progression, unacceptable toxicities, or the patient's condition meets the withdrawal criteria. The primary end point is the centrally reviewed overall response rate. The secondary end points include the disease control rate, overall survival, progression-free survival, and adverse events.

CONCLUSION: This phase II trial evaluating first-line combination chemotherapy for unresectable MPM commenced in January 2018. This is the first prospective trial to evaluate the effect of an anti-programmed death-1 antibody combined with cisplatin and pemetrexed for unresectable MPM.}, } @article {pmid29850181, year = {2018}, author = {Ahmadzada, T and Reid, G and Kao, S}, title = {Biomarkers in malignant pleural mesothelioma: current status and future directions.}, journal = {Journal of thoracic disease}, volume = {10}, number = {Suppl 9}, pages = {S1003-S1007}, pmid = {29850181}, issn = {2072-1439}, } @article {pmid29845703, year = {2018}, author = {Saji, T and Nishita, M and Ogawa, H and Doi, T and Sakai, Y and Maniwa, Y and Minami, Y}, title = {Critical role of the Ror-family of receptor tyrosine kinases in invasion and proliferation of malignant pleural mesothelioma cells.}, journal = {Genes to cells : devoted to molecular & cellular mechanisms}, volume = {23}, number = {7}, pages = {606-613}, doi = {10.1111/gtc.12599}, pmid = {29845703}, issn = {1365-2443}, mesh = {Cell Line, Tumor ; Cell Proliferation ; Humans ; Lung Neoplasms/genetics/*metabolism ; Mesothelioma/genetics/*metabolism ; Mesothelioma, Malignant ; Receptor Tyrosine Kinase-like Orphan Receptors/genetics/*metabolism/physiology ; Signal Transduction ; }, abstract = {Malignant pleural mesothelioma (MPM) is a highly aggressive tumor with poor prognosis and closely related to exposure to asbestos. MPM is a heterogeneous tumor with three main histological subtypes, epithelioid, sarcomatoid, and biphasic types, among which sarcomatoid type shows the poorest prognosis. The Ror-family of receptor tyrosine kinases, Ror1 and Ror2, is expressed in various types of tumor cells at higher levels and affects their aggressiveness. However, it is currently unknown whether they are expressed in and involved in aggressiveness of MPM. Here, we show that Ror1 and Ror2 are expressed in clinical specimens and cell lines of MPM with different histological features. Studies using MPM cell lines indicate that expression of Ror2 is associated tightly with high invasiveness of MPM cells, whereas Ror1 can contribute to their invasion in the absence of Ror2. However, both Ror1 and Ror2 promote proliferation of MPM cells. We also show that promoted invasion and proliferation of MPM cells by Ror signaling can be mediated by the Rho-family of small GTPases, Rac1, and Cdc42. These findings elucidate the critical role of Ror signaling in promoting invasion and proliferation of MPM cells.}, } @article {pmid29845408, year = {2018}, author = {Tartarone, A and Lerose, R and Aieta, M}, title = {Is there a role for immunotherapy in malignant pleural mesothelioma?.}, journal = {Medical oncology (Northwood, London, England)}, volume = {35}, number = {7}, pages = {98}, pmid = {29845408}, issn = {1559-131X}, mesh = {Antineoplastic Agents/*therapeutic use ; CTLA-4 Antigen/antagonists & inhibitors ; Clinical Trials as Topic ; Combined Modality Therapy ; Humans ; *Immunotherapy ; Lung Neoplasms/*therapy ; Mesothelioma/*therapy ; Mesothelioma, Malignant ; Pleural Neoplasms/*therapy ; Programmed Cell Death 1 Ligand 2 Protein/antagonists & inhibitors ; Programmed Cell Death 1 Receptor/antagonists & inhibitors ; }, abstract = {Malignant pleural mesothelioma (MPM) is a very aggressive malignancy, mainly caused by asbestos exposure. Patients with MPM have a poor prognosis that remained substantially unchanged in the last few years and limited effective therapeutic options with no recognized second or further-line therapy. In this context, also in view of the positive results observed in other tumor types, immunotherapy could play a relevant role. This review focuses on the most promising immunotherapies being investigated in MPM.}, } @article {pmid29794065, year = {2018}, author = {Butnor, KJ and Rueckert, J and Pavlisko, EN and Sporn, TA and Roggli, VL}, title = {Malignant peritoneal mesothelioma in patients with endometriosis.}, journal = {Journal of clinical pathology}, volume = {71}, number = {11}, pages = {971-974}, doi = {10.1136/jclinpath-2018-205099}, pmid = {29794065}, issn = {1472-4146}, mesh = {Adult ; Asbestos/adverse effects ; Biomarkers, Tumor/analysis ; Biopsy ; Endometriosis/etiology/*pathology ; Environmental Exposure/adverse effects ; Female ; Humans ; Lung Neoplasms/chemistry/etiology/*pathology ; Mesothelioma/chemistry/etiology/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Peritoneal Neoplasms/chemistry/etiology/*pathology ; Peritoneum/chemistry/*pathology ; Retrospective Studies ; Risk Factors ; Tertiary Care Centers ; }, abstract = {AIMS: Florid mesothelial hyperplasia is known to result from endometriosis. Well-differentiated papillary mesothelioma and multiloculated peritoneal inclusion cysts have also been described in women with endometriosis. To our knowledge, peritoneal diffuse malignant mesothelioma (MM) arising in the setting of endometriosis has not been reported. The purpose of this study is to report the clinicopathological characteristics of women with MM and endometriosis.

METHODS: The surgical pathology files of a tertiary academic medical centre and the consultation files of one of the study authors were reviewed for cases of MM in females with and without endometriosis.

RESULTS: Six women with MM and endometriosis ranging in age from 29 to 55 years (median=45 years) were identified. All had peritoneal MM and endometriosis involving the peritoneum and/or adnexa. Five had epithelioid MM and one had biphasic MM. Two had paraoccupational exposure to asbestos. The median age of women with MM and endometriosis (44.5 years) was significantly less than the median age of cases without endometriosis (58.0 years) (p value=0.01).

CONCLUSIONS: To our knowledge, this is the first report of MM in women with endometriosis. Interestingly, MM in the setting of endometriosis has only been observed in the peritoneum and not in other serosal cavities. The findings in the present study suggest that chronic serosal inflammation secondary to endometriosis may be an inducing factor in rare cases of MM of the peritoneum.}, } @article {pmid29792222, year = {2018}, author = {Kerger, BD}, title = {Longevity and pleural mesothelioma: age-period-cohort analysis of incidence data from the Surveillance, Epidemiology, and End Results (SEER) Program, 1973-2013.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {337}, pmid = {29792222}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; *Aging ; Child ; Child, Preschool ; Cohort Studies ; Female ; Humans ; Infant ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/*epidemiology ; Registries/*statistics & numerical data ; United States/epidemiology ; Young Adult ; }, abstract = {OBJECTIVE: This study investigates the hypothesis that an increasing fraction of incident pleural mesothelioma (PM) in the US population may be related to longevity, i.e., to expansion of the population over age 75 years with an age-related elevation in risk. An age-period-cohort analysis of the SEER 9 cancer registries (1973-2013) was conducted using 5-year intervals of age, calendar period, and birth cohort after stratification into four gender-age groups (male and female; 0-74 and 75+ years).

RESULTS: Gender-specific time trends in age-adjusted PM incidence by age groups were observed. After adjusting for cohort effects, males in the 0-74-year age group experienced rapidly declining PM incidence rates following the observed peak in 1978-1982, whereas continuously increasing incidence rates were observed among older males. A significant cohort effect was also observed among males in both age groups, with peak incidence rates in the 1926-1930/1928-1932 birth cohorts and thereafter. The distinct period and cohort effects among males age 0-74 years may be driven by declining age-adjusted PM incidence rates corresponding to the decline in occupational asbestos exposures post-World War II, whereas the increasing time trend seen in both genders at age 75+ may reflect an increasing proportion due to longevity-related factors.}, } @article {pmid29779004, year = {2018}, author = {Ugelvig Petersen, K and Volk, J and Kaerlev, L and Lyngbeck Hansen, H and Hansen, J}, title = {Cancer incidence among merchant seafarers: an extended follow-up of a Danish cohort.}, journal = {Occupational and environmental medicine}, volume = {75}, number = {8}, pages = {582-585}, doi = {10.1136/oemed-2018-105037}, pmid = {29779004}, issn = {1470-7926}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Cohort Studies ; Denmark/epidemiology ; Employment ; Female ; Follow-Up Studies ; Gastrointestinal Neoplasms/epidemiology/etiology ; Humans ; Incidence ; Lip Neoplasms/epidemiology/etiology ; Lung Neoplasms/epidemiology/etiology ; Male ; Mesothelioma/epidemiology/etiology ; Mesothelioma, Malignant ; Middle Aged ; Neoplasms/*epidemiology/etiology ; Occupational Diseases/*epidemiology/etiology ; Occupational Exposure/*adverse effects ; *Occupations ; Respiratory Tract Neoplasms/epidemiology/etiology ; Sex Factors ; *Ships ; Ultraviolet Rays/adverse effects ; Urogenital Neoplasms/epidemiology/etiology ; }, abstract = {OBJECTIVES: While maritime safety generally has improved dramatically over the last century, modern seafarers are still faced with numerous occupational hazards potentially affecting their risk of chronic diseases such as cancer. The aim of this study is to offer updated information on the incidence of specific cancers among both male and female seafarers.

METHODS: Using records from the Danish Seafarer Registry, all seafarers employed on Danish ships during 1986-1999 were identified, resulting in a cohort of 33 084 men and 11 209 women. Information on vital status and cancer was linked to each member of the cohort from the Danish Civil Registration System and the Danish Cancer Registry using the unique Danish personal identification number. SIRs were estimated for specific cancers using national rates.

RESULTS: The overall incidence of cancer was increased for both male and female seafarers (SIR 1.19, 95% CI 1.15 to 1.23, and SIR 1.14, 95% CI 1.07 to 1.22) compared with the general population. This excess was primarily driven by increases in gastrointestinal, respiratory and genitourinary cancers. In addition, male seafarers working in areas with asbestos exposure showed significantly increased risk of mesothelioma. Finally, the male seafarers had an increased risk of lip cancer.

CONCLUSIONS: The majority of cancers among seafarers continue to be lifestyle-related. However, occupational exposure to asbestos and ultraviolet radiation seems to affect the cancer pattern among the male seafarers as well.}, } @article {pmid29774715, year = {2018}, author = {Chellini, E and Battisti, F and Pellegri, M and Baldacci, M and Sallese, D and Cristaudo, A and Sartorelli, P and Arcangeli, G and Paoli, M and Fani, S and Festa, G and Calà, P}, title = {[Health surveillance programme for workers with past asbestos exposure in Tuscany Region (Central Italy)].}, journal = {Epidemiologia e prevenzione}, volume = {42}, number = {2}, pages = {171-177}, doi = {10.19191/EP18.2.P171.047}, pmid = {29774715}, issn = {1120-9763}, mesh = {Aged ; Aged, 80 and over ; Air Pollutants, Occupational/*toxicity ; Asbestos/*toxicity ; Asbestosis/complications/diagnosis/*epidemiology ; Diagnostic Screening Programs ; Female ; Humans ; Italy/epidemiology ; Male ; Mesothelioma/diagnosis/*epidemiology/etiology ; Middle Aged ; Occupational Exposure ; Pleural Neoplasms/diagnosis/*epidemiology/etiology ; *Population Surveillance ; Program Evaluation ; Stakeholder Participation ; }, abstract = {Asbestos-related diseases are characterized by a long latency time since exposure. This accounts for a health surveillance programme addressed to asbestos workers to be performed for decades after the cessation of occupational exposure. We describe the health surveillance programme for former asbestos-exposed workers in Tuscany Region (Central Italy), with particular attention to organization and related critical issues. The Deliberation of the Regional Administration of Tuscany (No. 396/2016) supports the programme, defined by a regional group of experts, and defines the public health services where the programme has to be implemented. The programme activities are classified in two levels: a first level for a basic health evaluation and a second level for in-depth analyses. The former asbestos workers, aged less than 80 years and with cessation of occupational asbestos exposure in the last 30 years, that might be included free of charge in the programme are about 5.600. The funds assigned to develop the programme from 2016 to 2024 were 2,044,808 euros. The Regional Administration of Tuscany decided to offer and guarantee a homogeneous programme in the whole region. The identification of a specific public health programme and the cooperation of social stakeholders, defined with specific regional agreements, might facilitate to overcome the problems which are still open, such as a broaden invitation to adhere to the programme, an extended knowledge on the service, and the application of a similar health programme for still-working former asbestos workers.}, } @article {pmid29774711, year = {2018}, author = {Caputo, A and De Santis, M and Manno, V and Cauzillo, G and Bruni, BM and Palumbo, L and Conti, S and Comba, P}, title = {[Health impact of asbestos fibres naturally occurring in Mount Pollino area (Basilicata Region, Southern Italy)].}, journal = {Epidemiologia e prevenzione}, volume = {42}, number = {2}, pages = {142-150}, doi = {10.19191/EP18.2.P142.043}, pmid = {29774711}, issn = {1120-9763}, mesh = {Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Asbestosis/*etiology/mortality ; Environmental Exposure ; Environmental Monitoring ; Environmental Pollutants/*toxicity ; Female ; Geography, Medical ; Geological Phenomena ; Hospitalization/statistics & numerical data ; Humans ; Incidence ; Italy ; Male ; Mesothelioma/etiology/mortality ; Mineral Fibers/toxicity ; Ovarian Neoplasms/mortality ; Population Surveillance ; Respiratory Tract Neoplasms/etiology/mortality ; }, abstract = {OBJECTIVES: to estimate the health impact of asbestos fibres naturally occurring in Mount Pollino area (Basilicata Region, Southern Italy).

DESIGN: geographic mortality, hospitalization, and incidence study. Setting and participant s: population resident in 12 Municipalities of Mount Pollino area with naturally occurring asbestos fibres.

MAIN OUTCOME MEASURES: standardized mortality ratio (SMR) and standardized hospitalization rate (SHR) for asbestos-related diseases; standardized incidence ratio (SIR) for mesotheliomas. Result s: in the area of Mount Pollino, where asbestos fibres naturally occur, especially in the sub-area in which fibres are close to dwellings and settlements, it was observed: • a significant excess of mesothelioma incidence (SIR: 208; CI95% 111-355; 13 observed); • a non-significant excess of hospitalization for malignant pleural neoplasms (SHR: 176; CI95% 93-335; 9 observed); • a significant excess for mortality and hospitalization for pneumoconiosis (SMR: 534; CI95% 345-824; 20 observed - SHR: 245; CI95% 149-405; 15 observed); • a significant excess for hospitalization (SHR: 852; CI95% 290-2,506; 3 observed) for asbestosis.

CONCLUSION: it is necessary to continue environmental monitoring and environmental remediation in the area with higher asbestos exposure. It is suggested to implement a permanent process of epidemiological surveillance in this same area. A communication plan with local administrators, general practitioners, school teachers, media, and the resident population at large should be realized.}, } @article {pmid29774705, year = {2018}, author = {Terracini, B}, title = {[Parliamentary committee of inquiry about health of Italian soldiers exposed to uranium, asbestos, and vaccines].}, journal = {Epidemiologia e prevenzione}, volume = {42}, number = {2}, pages = {114-115}, doi = {10.19191/EP18.2.P114.037}, pmid = {29774705}, issn = {1120-9763}, mesh = {*Advisory Committees ; Asbestos/*adverse effects ; Forecasting ; Government Agencies ; Humans ; Italy/epidemiology ; Mesothelioma/epidemiology/etiology ; *Military Personnel ; Occupational Diseases/*epidemiology/etiology ; *Occupational Exposure ; Uranium/*adverse effects ; Vaccines/*adverse effects ; }, } @article {pmid29772681, year = {2018}, author = {Furuya, S and Chimed-Ochir, O and Takahashi, K and David, A and Takala, J}, title = {Global Asbestos Disaster.}, journal = {International journal of environmental research and public health}, volume = {15}, number = {5}, pages = {}, pmid = {29772681}, issn = {1660-4601}, mesh = {Asbestosis/diagnosis/*epidemiology/etiology/prevention & control ; Cost of Illness ; Global Health/*statistics & numerical data ; Humans ; Mesothelioma/diagnosis/*epidemiology/etiology/prevention & control ; }, abstract = {Introduction: Asbestos has been used for thousands of years but only at a large industrial scale for about 100[-]150 years. The first identified disease was asbestosis, a type of incurable pneumoconiosis caused by asbestos dust and fibres. The latest estimate of global number of asbestosis deaths from the Global Burden of Disease estimate 2016 is 3495. Asbestos-caused cancer was identified in the late 1930's but despite today's overwhelming evidence of the strong carcinogenicity of all asbestos types, including chrysotile, it is still widely used globally. Various estimates have been made over time including those of World Health Organization and International Labour Organization: 107,000[-]112,000 deaths. Present estimates are much higher. Objective: This article summarizes the special edition of this Journal related to asbestos and key aspects of the past and present of the asbestos problem globally. The objective is to collect and provide the latest evidence of the magnitude of asbestos-related diseases and to provide the present best data for revitalizing the International Labor Organization/World Health Organization Joint Program on Asbestos-related Diseases. Methods: Documentation on asbestos-related diseases, their recognition, reporting, compensation and prevention efforts were examined, in particular from the regulatory and prevention point of view. Estimated global numbers of incidence and mortality of asbestos-related diseases were examined. Results: Asbestos causes an estimated 255,000 deaths (243,223[-]260,029) annually according to latest knowledge, of which work-related exposures are responsible for 233,000 deaths (222,322[-]242,802). In the European Union, United States of America and in other high income economies (World Health Organization regional classification) the direct costs for sickness, early retirement and death, including production losses, have been estimated to be very high; in the Western European countries and European Union, and equivalent of 0.70% of the Gross Domestic Product or 114 × 10[8] United States Dollars. Intangible costs could be much higher. When applying the Value of Statistical Life of 4 million EUR per cancer death used by the European Commission, we arrived at 410 × 10[8] United States Dollars loss related to occupational cancer and 340 × 10[8] related to asbestos exposure at work, while the human suffering and loss of life is impossible to quantify. The numbers and costs are increasing practically in every country and region in the world. Asbestos has been banned in 55 countries but is used widely today; some 2,030,000 tons consumed annually according to the latest available consumption data. Every 20 tons of asbestos produced and consumed kills a person somewhere in the world. Buying 1 kg of asbestos powder, e.g., in Asia, costs 0.38 United States Dollars, and 20 tons would cost in such retail market 7600 United States Dollars. Conclusions: Present efforts to eliminate this man-made problem, in fact an epidemiological disaster, and preventing exposures leading to it are insufficient in most countries in the world. Applying programs and policies, such as those for the elimination of all kind of asbestos use-that is banning of new asbestos use and tight control and management of existing structures containing asbestos-need revision and resources. The International Labor Organization/World Health Organization Joint Program for the Elimination of Asbestos-Related Diseases needs to be revitalized. Exposure limits do not protect properly against cancer but for asbestos removal and equivalent exposure elimination work, we propose a limit value of 1000 fibres/m[3].}, } @article {pmid29753121, year = {2018}, author = {Armato, SG and Nowak, AK}, title = {Revised Modified Response Evaluation Criteria in Solid Tumors for Assessment of Response in Malignant Pleural Mesothelioma (Version 1.1).}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {13}, number = {7}, pages = {1012-1021}, doi = {10.1016/j.jtho.2018.04.034}, pmid = {29753121}, issn = {1556-1380}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Humans ; Lung Neoplasms/diagnostic imaging/drug therapy/*pathology ; Mesothelioma/diagnostic imaging/drug therapy/*pathology ; Mesothelioma, Malignant ; Pleural Neoplasms/diagnostic imaging/drug therapy/*pathology ; *Response Evaluation Criteria in Solid Tumors ; Survival Rate ; Tomography, X-Ray Computed/methods ; Treatment Outcome ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma poses unique difficulties in tumor measurement and response assessment; however, robust and reproducible assessment of response is critically important in the conduct, interpretation, and reporting of clinical trials.

METHODS: The current de facto standard for the assessment of mesothelioma tumor response, "modified RECIST" (Response Evaluation Criteria in Solid Tumors), was published in 2004 as a research paper. Practical application of the modified RECIST guidelines has suffered from varied interpretations, resulting in inaccuracies and inconsistencies in tumor response assessment across and within mesothelioma clinical trials. The presented "modified RECIST 1.1 for mesothelioma" response assessment guidelines provide a much-needed update that incorporates recommendations from RECIST 1.1 and approaches to other practical issues, including: (1) definition of minimally measurable disease; (2) definition of measurable lesions; (3) acceptable measurement location; (4) non-pleural disease considerations; (5) characterization of non-measurable pleural disease; (6) assessment of pathological lymph nodes; (7) establishing progressive disease; and (8) accommodations for bilateral pleural disease.

RESULTS: These modified RECIST 1.1 guidelines for mesothelioma tumor response collate and apply research published since the development of modified RECIST, align modified RECIST with RECIST 1.1, address those aspects of tumor measurement that were neglected or not well characterized in the modified RECIST paper, and clarify ambiguous or difficult measurement issues that have been highlighted through the subsequent decade of clinical trials research.

CONCLUSION: Adoption of the modified RECIST 1.1 guidelines for mesothelioma is recommended to harmonize the application of tumor measurement and response assessment across the next generation of clinical trials in this disease.}, } @article {pmid29742950, year = {2018}, author = {Arnoldussen, YJ and Skaug, V and Aleksandersen, M and Ropstad, E and Anmarkrud, KH and Einarsdottir, E and Chin-Lin, F and Granum Bjørklund, C and Kasem, M and Eilertsen, E and Apte, RN and Zienolddiny, S}, title = {Inflammation in the pleural cavity following injection of multi-walled carbon nanotubes is dependent on their characteristics and the presence of IL-1 genes.}, journal = {Nanotoxicology}, volume = {12}, number = {6}, pages = {522-538}, doi = {10.1080/17435390.2018.1465139}, pmid = {29742950}, issn = {1743-5404}, mesh = {Animals ; Asbestos, Crocidolite/toxicity ; Fibrosis ; Inflammation/*chemically induced ; Interleukin-1/*genetics ; Mice ; Mice, Inbred C57BL ; Nanotubes, Carbon/*toxicity ; Pleural Cavity/*drug effects/pathology ; }, abstract = {Upon inhalation, multi-walled carbon nanotubes (MWCNTs) may reach the subpleura and pleural spaces, and induce pleural inflammation and/or mesothelioma in humans. However, the mechanisms of MWCNT-induced pathology after direct intrapleural injections are still only partly elucidated. In particular, a role of the proinflammatory interleukin-1 (IL-1) cytokines in pleural inflammation has so far not been published. We examined the MWCNT-induced pleural inflammation, gene expression abnormalities, and the modifying role of IL-1α and β cytokines following intrapleural injection of two types of MWCNTs (CNT-1 and CNT-2) compared with crocidolite asbestos in IL-1 wild-type (WT) and IL-1α/β KO (IL1-KO) mice. Histopathological examination of the pleura 28 days post-exposure revealed mesothelial cell hyperplasia, leukocyte infiltration, and fibrosis occurring in the CNT-1 (Mitsui-7)-exposed group. The pleura of these mice also showed the greatest changes in mRNA and miRNA expression levels, closely followed by CNT-2. In addition, the CNT-1-exposed group also presented the greatest infiltrations of leukocytes and proliferation of fibrous tissue. WT mice were more prone to development of sustained inflammation and fibrosis than IL1-KO mice. Prominent differences in genetic and epigenetic changes were also observed between the two genotypes. In conclusion, the fibrotic response to MWCNTs in the pleura depends on the particles' physico-chemical properties and on the presence or absence of the IL-1 genes. Furthermore, we found that CNT-1 was the most potent inducer of inflammatory responses, followed by CNT-2 and crocidolite asbestos.}, } @article {pmid29738812, year = {2018}, author = {Asgharian, B and Owen, TP and Kuempel, ED and Jarabek, AM}, title = {Dosimetry of inhaled elongate mineral particles in the respiratory tract: The impact of shape factor.}, journal = {Toxicology and applied pharmacology}, volume = {361}, number = {}, pages = {27-35}, pmid = {29738812}, issn = {1096-0333}, support = {CC999999//Intramural CDC HHS/United States ; }, mesh = {Asbestos/toxicity ; Computer Simulation ; Humans ; Inhalation Exposure/*adverse effects ; Minerals/*toxicity ; Occupational Exposure ; Particle Size ; Particulate Matter/*toxicity ; Respiratory Tract Diseases/*chemically induced ; Risk Assessment ; }, abstract = {Inhalation exposure to some types of fibers (e.g., asbestos) is well known to be associated with respiratory diseases and conditions such as pleural plaques, fibrosis, asbestosis, lung cancer, and mesothelioma. In recent years, attention has expanded to other types of elongate mineral particles (EMPs) that may share similar geometry with asbestos fibers but which may differ in mineralogy. Inhalability, dimensions and orientation, and density are major determinants of the aerodynamic behavior for fibers and other EMPs; and the resultant internal dose is recognized as being the critical link between exposure and pathogenesis. Insufficient data are available to fully understand the role of specific physicochemical properties on the potential toxicity across various types of fiber materials. While additional information is required to assess the potential health hazards of EMPs, dosimetry models are currently available to estimate the initially deposited internal dose, which is an essential step in linking airborne exposures to potential health risks. Based on dosimetry model simulations, the inhalability and internal dose of EMPs were found to be greater than that of spherical particles having the same mass or volume. However, the complexity of the dependence of internal dose on EMPs dimensions prevented a straightforward formulation of the deposition-dimension (length or diameter) relationship. Because health outcome is generally related to internal dose, consideration of the factors that influence internal dose is important in assessing the potential health hazards of airborne EMPs.}, } @article {pmid29737238, year = {2017}, author = {Metintas, S and Ak, G and Bogar, F and Yilmaz, S and Metintas, M}, title = {Asbestos knowledge and awareness level in central part of Anatolia.}, journal = {International journal of occupational and environmental health}, volume = {23}, number = {3}, pages = {243-249}, pmid = {29737238}, issn = {2049-3967}, mesh = {Adult ; Aged ; *Asbestos ; *Environmental Exposure ; Female ; *Health Knowledge, Attitudes, Practice ; Humans ; Male ; Middle Aged ; *Rural Population/statistics & numerical data ; Turkey ; Young Adult ; }, abstract = {Background Asbestos-contaminated soil has been used by people for many years in the rural part of Anatolia. However, there is no program to control usage of asbestos in this region. Objective To determine the knowledge and awareness level about asbestos in a region where asbestos-related diseases are endemic due to environmental exposure to asbestos in the rural setting. Methods This study included 760 participants, recruited using non-probability sampling, who were classified into four groups according to residence and asbestos exposure type (urban, rural; asbestos-exposed, asbestos-unexposed). Asbestos knowledge and awareness was measured via the Asbestos Knowledge and Awareness Questionnaire (AKAQ). The cut-off value of questionnaire was determined by the K-means cluster analysis for sufficient and insufficient knowledge and awareness level. A multiple logistic regression analysis was performed to determine independent factors affecting sufficient knowledge and awareness of participants about asbestos. Results The median and mean score of the AKAQ in study group were 30 and 33.9, respectively. The urban asbestos-exposed group had a higher score than the urban asbestos-unexposed and both rural groups (p < 0.001). Factors affecting asbestos knowledge and awareness were education status (p = 0.035), asbestos exposure (p = 0.003) and living in the rural area (p = 0.005). Sufficient knowledge and awareness (score > 45) was higher among participants who had graduated from university and had asbestos exposure. Insufficient knowledge and awareness level was higher among participants living in rural areas. Conclusion In this region of Anatolia, knowledge and awareness level of asbestos was low among people at risk for environmental asbestos exposure. People should be aware of asbestos and its hazards by a well-designed training program and be monitored for asbestos-related diseases.}, } @article {pmid29733442, year = {2018}, author = {Baur, X}, title = {Review on the adverse health effects of asbestiform antigorite, a non-regulated asbestiform serpentine mineral.}, journal = {American journal of industrial medicine}, volume = {61}, number = {7}, pages = {625-630}, doi = {10.1002/ajim.22857}, pmid = {29733442}, issn = {1097-0274}, mesh = {Animals ; Asbestos, Serpentine/*adverse effects/chemistry/toxicity ; Asbestosis/epidemiology/*etiology ; Humans ; Lung Neoplasms/*chemically induced/epidemiology ; Mesothelioma/*chemically induced/epidemiology ; *Mining ; Occupational Exposure/*adverse effects/statistics & numerical data ; }, abstract = {BACKGROUND: Although antigorite is generally described as platy, its fibrous (asbestiform) variant is present widespread in serpentinite rocks. In addition to its primarily fibrous occurrence, asbestiform antigorite may also be formed from serpentinite with massive appearance during tunneling and mining. It is not of commercial interest, but exposure may occur in the certain environments.

METHODS AND RESULTS: Detailed studies of the structural features of this antigorite type revealed characteristics closely related to those of chrysotile. Therefore, it is plausible that this serpentine mineral may present a similar health risk for exposed subjects. This is in agreement with results from clinical and animal studies, as well as in vitro experiments showing the cytotoxic, fibrogenic, and carcinogenic potential of antigorite, similar to that of chrysotile and amphibole asbestos.

CONCLUSIONS: Current evidence supports a need for an update to existing regulations to include unregulated asbestiform antigorite, similar to regulatory measures taken for asbestos.}, } @article {pmid29723687, year = {2018}, author = {Galateau Salle, F and Le Stang, N and Nicholson, AG and Pissaloux, D and Churg, A and Klebe, S and Roggli, VL and Tazelaar, HD and Vignaud, JM and Attanoos, R and Beasley, MB and Begueret, H and Capron, F and Chirieac, L and Copin, MC and Dacic, S and Danel, C and Foulet-Roge, A and Gibbs, A and Giusiano-Courcambeck, S and Hiroshima, K and Hofman, V and Husain, AN and Kerr, K and Marchevsky, A and Nabeshima, K and Picquenot, JM and Rouquette, I and Sagan, C and Sauter, JL and Thivolet, F and Travis, WD and Tsao, MS and Weynand, B and Damiola, F and Scherpereel, A and Pairon, JC and Lantuejoul, S and Rusch, V and Girard, N}, title = {New Insights on Diagnostic Reproducibility of Biphasic Mesotheliomas: A Multi-Institutional Evaluation by the International Mesothelioma Panel From the MESOPATH Reference Center.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {13}, number = {8}, pages = {1189-1203}, pmid = {29723687}, issn = {1556-1380}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Biopsy ; Female ; Humans ; Immunohistochemistry ; Lung Neoplasms/*diagnosis/pathology ; Male ; Mesothelioma/*diagnosis/pathology ; Mesothelioma, Malignant ; Reproducibility of Results ; }, abstract = {INTRODUCTION: The 2015 WHO classification of tumors categorized malignant mesothelioma into epithelioid, biphasic (BMM), and sarcomatoid (SMM) for prognostic relevance and treatment decisions. The survival of BMM is suspected to correlate with the amount of the sarcomatoid component. The criteria for a sarcomatoid component and the interobserver variability between pathologists for identifying this component are not well described. In ambiguous cases, a "transitional" (TMM) subtype has been proposed but was not accepted as a specific subtype in the 2015 WHO classification. The aims of this study were to evaluate the interobserver agreement in the diagnosis of BMM, to determine the nature and the significance of TMM subtype, and to relate the percentage of sarcomatoid component with survival. The value of staining for BRCA-1-associated protein (BAP1) and CDKN2A(p16) fluorescence in situ hybridization (FISH) were also assessed with respect to each of the tumoral components.

METHODS: The study was conducted by the International Mesothelioma Panel supported by the French National Cancer Institute, the network of rare cancer (EURACAN) and in collaboration with the International Association for the Study of Lung Cancer (IASLC). The patient cases include a random group of 42 surgical biopsy samples diagnosed as BMM with evaluation of SMM component by the French Panel of MESOPATH experts was selected from the total series of 971 BMM cases collected from 1998 to 2016. Fourteen international pathologists with expertise in mesothelioma reviewed digitally scanned slides (hematoxylin and eosin - stained and pan-cytokeratin) without knowledge of prior diagnosis or outcome. Cases with at least 7 of 14 pathologists recognizing TMM features were selected as a TMM group. Demographic, clinical, histopathologic, treatment, and follow-up data were retrieved from the MESOBANK database. BAP1 (clone C-4) loss and CDKN2A(p16) homozygous deletion (HD) were assessed by immunohistochemistry (IHC) and FISH, respectively. Kappa statistics were applied for interobserver agreement and multivariate analysis with Cox regression adjusted for age and gender was performed for survival analysis.

RESULTS: The 14 panelists recorded a total of 544 diagnoses. The interobserver correlation was moderate (weighted Kappa = 0.45). Of the cases originally classified as BMM by MESOPATH, the reviewers agreed in 71% of cases (385 of 544 opinions), with cases classified as pure epithelioid in 17% (93 of 544), and pure sarcomatoid in 12% (66 of 544 opinions). Diagnosis of BMM was made on morphology or IHC alone in 23% of the cases and with additional assessment of IHC in 77% (402 of 544). The median overall survival (OS) of the 42 BMM cases was 8 months. The OS for BMM was significantly different from SMM and epithelioid malignant mesothelioma (p < 0.0001). In BMM, a sarcomatoid component of less than 80% correlated with a better survival (p = 0.02). There was a significant difference in survival between BMM with TMM showing a median survival at 6 months compared to 12 months for those without TMM (p < 0.0001). BAP1 loss was observed in 50% (21 of 42) of the total cases and in both components in 26%. We also compared the TMM group to that of more aggressive patterns of epithelioid subtypes of mesothelioma (solid and pleomorphic of our large MESOPATH cohort). The curve of transitional type was persistently close to the OS curve of the sarcomatoid component. The group of sarcomatoid, transitional, and pleomorphic mesothelioma were very close to each other. We then considered the contribution of BAP1 immunostaining and loss of CDKN2A(p16) by FISH. BAP1 loss was observed in 50% (21 of 41) of the total cases and in both component in 27% of the cases (11 of 41). There was no significant difference in BAP1 loss between the TMM and non-TMM groups. HD CDKN2A(p16) was detected in 74% of the total cases with no significant difference between the TMM and non-TMM groups. In multivariate analysis, TMM morphology was an indicator of poor prognosis with a hazard ratio = 3.2; 95% confidence interval: 1.6 - 8.0; and p = 0.003 even when compared to the presence of HD CDKN2A(p16) on sarcomatoid component (hazard ratio = 4.5; 95% confidence interval: 1.2 - 16.3, p = 0.02).

CONCLUSIONS: The interobserver concordance among the international mesothelioma and French mesothelioma panel suggests clinical utility for an updated definition of biphasic mesothelioma that allows better stratification of patients into risk groups for treatment decisions, systemic anticancer therapy, or selection for surgery or palliation. We also have shown the usefulness of FISH detection of CDKN2A(p16) HD compared to BAP1 loss on the spindle cell component for the separation in ambiguous cases between benign florid stromal reaction from true sarcomatoid component of biphasic mesothelioma. Taken together our results further validate the concept of transitional pattern as a poor prognostic indicator.}, } @article {pmid29723551, year = {2018}, author = {Garcia, E and Newfang, D and Coyle, JP and Blake, CL and Spencer, JW and Burrelli, LG and Johnson, GT and Harbison, RD}, title = {Evaluation of airborne asbestos exposure from routine handling of asbestos-containing wire gauze pads in the research laboratory.}, journal = {Regulatory toxicology and pharmacology : RTP}, volume = {96}, number = {}, pages = {135-141}, doi = {10.1016/j.yrtph.2018.04.020}, pmid = {29723551}, issn = {1096-0295}, mesh = {*Absorbent Pads ; Air Pollution, Indoor/*analysis ; Asbestos/administration & dosage/*analysis ; *Environmental Monitoring ; Humans ; *Laboratories ; *Research ; }, abstract = {Three independently conducted asbestos exposure evaluations were conducted using wire gauze pads similar to standard practice in the laboratory setting. All testing occurred in a controlled atmosphere inside an enclosed chamber simulating a laboratory setting. Separate teams consisting of a laboratory technician, or technician and assistant simulated common tasks involving wire gauze pads, including heating and direct wire gauze manipulation. Area and personal air samples were collected and evaluated for asbestos consistent with the National Institute of Occupational Safety Health method 7400 and 7402, and the Asbestos Hazard Emergency Response Act (AHERA) method. Bulk gauze pad samples were analyzed by Polarized Light Microscopy and Transmission Electron Microscopy to determine asbestos content. Among air samples, chrysotile asbestos was the only fiber found in the first and third experiments, and tremolite asbestos for the second experiment. None of the air samples contained asbestos in concentrations above the current permissible regulatory levels promulgated by OSHA. These findings indicate that the level of asbestos exposure when working with wire gauze pads in the laboratory setting is much lower than levels associated with asbestosis or asbestos-related lung cancer and mesothelioma.}, } @article {pmid29719805, year = {2018}, author = {Sattar, N and Durrance, R and Khan, A and Patel, N and Mora, M and Shalonov, A}, title = {Malignant mesothelioma presenting as recurrent hydro-pneumothorax: An atypical case presentation and literature review.}, journal = {Respiratory medicine case reports}, volume = {23}, number = {}, pages = {152-155}, pmid = {29719805}, issn = {2213-0071}, abstract = {Malignant Pleural Mesothelioma (MPM) is a rare pleural malignancy, with a vague presentation complicated by a decades-long latency period between environmental exposure and clinical manifestations. Spontaneous hydro-pneumothorax is a rare presentation of MPM, most often requiring invasive tissue biopsy to confirm the etiologic diagnosis. We present the case of 79-year-old male smoker with no documented history of asbestos exposure, who was found to have MPM after presenting with dyspnea and subsequently found to have recurrent hydro-pneumothorax. On Literature review of the limited documented cases of MPM with hydro-pneumothorax, we found an exclusively male population with a significant smoking history, a marked right sided pathology predominance, and a generally poor prognosis. While this corresponds with the examined case, and suggests that the presence of hydro-pneumothorax implies a high-grade tumor and significant tissue invasion, and therefore poor prognosis similar to that of stage 4 disease, it differs from more generalized case reviews of MPM, most importantly in their anatomical descriptions, prognostic indicators, and epidemiologic tendencies.}, } @article {pmid29714657, year = {2019}, author = {Barbieri, PG and Mirabelli, D and Magnani, C and Brollo, A}, title = {On the diagnosis of malignant pleural mesothelioma: A necropsy-based study of 171 cases (1997-2016).}, journal = {Tumori}, volume = {105}, number = {4}, pages = {304-311}, doi = {10.1177/0300891618765538}, pmid = {29714657}, issn = {2038-2529}, mesh = {Asbestos/adverse effects ; Autopsy/methods ; Humans ; Immunohistochemistry/methods ; Lung Neoplasms/*diagnosis ; Mesothelioma/*diagnosis ; Mesothelioma, Malignant ; Pleural Diseases/*diagnosis ; Pleural Effusion/diagnosis ; Pleural Neoplasms/*diagnosis ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) diagnosis is known to be difficult. We report on the diagnostic elements available in life in an MPM necropsy case series and describe the frequency of non-neoplastic asbestos-related diseases as biological exposure indices.

METHODS: We reviewed pathologic and clinical records of an unselected series of autopsies (1977-2016) in patients with MPM employed in the Monfalcone shipyards or living with shipyard workers. We assessed the consistency with autopsy results of diagnoses based on, respectively, radiologic, cytologic, and histologic findings, with and without immunophenotyping.

RESULTS: Data on 171 cases were available: for 169, autopsy confirmed the MPM diagnosis. In life, 119 cases had histologic confirmation of diagnosis, whereas 7 were negative; all cases without immunophenotypization were autoptic MPMs. Cytology alone had been positive in 18 autoptic MPM cases, negative in 14. Radiologic imaging alone had been positive in another 16, negative in 11. In the 2 cases not confirmed at autopsy, MPM had been suspected by chest computed tomography only. Bilateral pleural plaques were found in 144 and histologic evidence of asbestosis in 62 cases.

CONCLUSIONS: Autopsies confirmed 169/171 cases, including cases that would not be considered as certain based on diagnosis in life. Radiologic imaging, cytologic examination of pleural effusions, or both combined had low sensitivity but high positive predictive value: when they are positive, proceeding to thoracoscopy should be justified. MPM has been correctly diagnosed even without immunohistochemistry. The prevalence of pleural plaques and asbestosis was high due to severity of asbestos exposures in these cases.}, } @article {pmid29709339, year = {2019}, author = {Wu, TH and Lee, LJ and Yuan, CT and Chen, TW and Yang, JC}, title = {Prognostic factors and treatment outcomes of malignant pleural mesothelioma in Eastern Asian patients - A Taiwanese study.}, journal = {Journal of the Formosan Medical Association = Taiwan yi zhi}, volume = {118}, number = {1 Pt 2}, pages = {230-236}, doi = {10.1016/j.jfma.2018.04.001}, pmid = {29709339}, issn = {0929-6646}, mesh = {Aged ; Databases, Factual ; Female ; Hospitals, University ; Humans ; Lung Neoplasms/diagnosis/*mortality/*therapy ; Male ; Mesothelioma/diagnosis/*mortality/*therapy ; Mesothelioma, Malignant ; Middle Aged ; Neoplasm Staging ; Pleural Neoplasms/diagnosis/*mortality/*therapy ; Prognosis ; Survival Analysis ; Taiwan/epidemiology ; }, abstract = {BACKGROUND/PURPOSE: There are scarce reports on the prognostic factors and treatment outcomes of patients with malignant pleural mesothelioma (MPM) in Asia. This study aimed to address these matters in a real-world setting.

METHODS: Medical records of patients with histologically proven MPM diagnosed between 1977 and 2016 at the National Taiwan University Hospital were reviewed. Variables including age, gender, performance status, asbestos exposure, smoking history, histology subtype, staging, and treatment received were recorded. All patients were followed until death or March 1st, 2017. Survival and prognostic factors were analyzed by the Kaplan-Meir method and the Cox proportional hazard model.

RESULTS: A total of 93 patients was identified, including 65 men and 28 women. An increasing trend of MPM cases diagnosed was observed in the past 40 years. Stage I/II disease (HR 0.24, 95% CI 0.13-0.46) and epithelioid histology (HR 0.42, 95% CI 0.23-0.75) were associated with favorable prognosis, whereas age ≥70 years (HR 2.66, 95% CI 1.36-5.22) and ECOG ≥2 (HR 5.03, 95% CI 2.69-9.4) were poor prognostic factors. After adjustment for prognostic factors, surgery in stage I-III MPM (HR 0.36, 95% CI 0.15-0.83) and systemic therapy in stage III/IV disease (HR 0.42, 95% CI 0.19-0.94) conferred a survival benefit.

CONCLUSION: This is one of the largest case series of MPM reported in Asia outside of Japan. Prognostic factors in the study population included age, performance status, stage, and histology subtype. Surgery in potentially resectable disease and systemic therapy in advanced MPM confer a survival benefit in Asian patients.}, } @article {pmid29701625, year = {2018}, author = {Barbiero, F and Zanin, T and Pisa, FE and Casetta, A and Rosolen, V and Giangreco, M and Negro, C and Bovenzi, M and Barbone, F}, title = {Mortality in a cohort of asbestos-exposed workers undergoing health surveillance.}, journal = {La Medicina del lavoro}, volume = {109}, number = {2}, pages = {83-86}, pmid = {29701625}, issn = {0025-7818}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Asbestosis/complications/*mortality ; Carcinogens ; Child ; Child, Preschool ; Cohort Studies ; Construction Materials/adverse effects ; Female ; Follow-Up Studies ; Humans ; Infant ; Infant, Newborn ; Italy/epidemiology ; Lung Neoplasms/etiology/*mortality ; Male ; Mesothelioma/etiology/*mortality ; Middle Aged ; Occupational Diseases/etiology/*mortality ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/etiology/*mortality ; Population Surveillance ; }, abstract = {BACKGROUND: The coastal area of Friuli Venezia Giulia (FVG) region, north-eastern Italy, was characterized by work activities in which asbestos was used until the early 1990s, particularly in shipbuilding. A public health surveillance program (PHSP) for asbestos-exposed workers was established, although limited evidence exists about the efficacy of such programs in reducing disease occurrence and mortality.

OBJECTIVES: To compare mortality in a cohort of 2,488 men occupationally exposed to asbestos, enrolled in a PHSP in FVG between the early 1990s and 2008, with that of the general population of FVG and Italy.

METHODS: Standardized Mortality Ratios (SMR), with 95% Confidence Interval (95% CI), for all causes, all cancers, lung (LC) and pleural cancer (PC) were estimated in the cohort and in subgroups of workers with the first hire in shipbuilding that caused asbestos exposure (<1974, 1974-1984, 1985-1994).

RESULTS: A strong excess in mortality for PC with reference to FVG (SMR=6.87, 95% CI 4.45-10.17) and Italian population (SMR=13.95, 95% CI 9.02-20.64) was observed. For LC, the FVG-based SMR was 1.49 (95% CI 1.17-1.89) and the Italy-based 1.43 (95% CI 1.12-1.81). Mortality among workers with the first hire in shipbuilding before 1974 was high for PC (FVG-based SMR=8.98, 95% CI 5.56-13.75; Italy-based SMR=18.41, 95% CI 11.40-28.17) and for LC (FVG-based SMR =1.60, 95% CI 1.18-2.11; Italy-based SMR=1.54, 95% CI 1.14-2.03). Further, for LC between 1974 and 1984, the FVG-based SMR was 2.45 (95% CI 1.06-4.82), and the Italy-based SMR was 2.33 (95% CI 1.01-4.60).

CONCLUSIONS: This cohort experienced an excess mortality for pleural and lung cancer, compared with regional and national populations. For lung cancer, the excess was stronger in workers with the first hire in shipbuilding before 1985, suggesting a key role of asbestos exposure.}, } @article {pmid29699512, year = {2018}, author = {Blum, W and Pecze, L and Rodriguez, JW and Steinauer, M and Schwaller, B}, title = {Regulation of calretinin in malignant mesothelioma is mediated by septin 7 binding to the CALB2 promoter.}, journal = {BMC cancer}, volume = {18}, number = {1}, pages = {475}, pmid = {29699512}, issn = {1471-2407}, support = {130680//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung/International ; 139226//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (CH)/International ; }, mesh = {Animals ; Base Sequence ; Butyrates/pharmacology ; Calbindin 2/chemistry/*genetics/metabolism ; Cell Cycle Proteins/*metabolism ; Cell Line, Tumor ; Cytokines/metabolism ; Enhancer Elements, Genetic ; *Gene Expression Regulation, Neoplastic/drug effects ; Genes, Reporter ; Humans ; Lung Neoplasms/*genetics/*metabolism/pathology ; Mesothelioma/*genetics/*metabolism/pathology ; Mesothelioma, Malignant ; Mice ; *Promoter Regions, Genetic ; Protein Binding ; Protein Transport ; Proteolysis ; Response Elements ; Septins/*metabolism ; }, abstract = {BACKGROUND: The calcium-binding protein calretinin (gene name: CALB2) is currently considered as the most sensitive and specific marker for the diagnosis of malignant mesothelioma (MM). MM is a very aggressive tumor strongly linked to asbestos exposure and with no existing cure so far. The mechanisms of calretinin regulation, as well as its distinct function in MM are still poorly understood.

METHODS: We searched for transcription factors binding to the CALB2 promoter and modulating calretinin expression. For this, DNA-binding assays followed by peptide shotgun-mass spectroscopy analyses were used. CALB2 promoter activity was assessed by dual-luciferase reporter assays. Furthermore, we analyzed the effects of CALB2 promoter-binding proteins by lentiviral-mediated overexpression or down-regulation of identified proteins in MM cells. The modulation of expression of such proteins by butyrate was determined by subsequent Western blot analysis. Immunohistochemical analysis of embryonic mouse lung tissue served to verify the simultaneous co-expression of calretinin and proteins interacting with the CALB2 promoter during early development. Finally, direct interactions of calretinin with target proteins were evidenced by co-immunoprecipitation experiments.

RESULTS: Septin 7 was identified as a butyrate-dependent transcription factor binding to a CALB2 promoter region containing butyrate-responsive elements (BRE) resulting in decreased calretinin expression. Accordingly, septin 7 overexpression decreased calretinin expression levels in MM cells. The regulation was found to operate bi-directionally, i.e. calretinin overexpression also decreased septin 7 levels. During murine embryonic development calretinin and septin 7 were found to be co-expressed in embryonic mesenchyme and undifferentiated mesothelial cells. In MM cells, calretinin and septin 7 colocalized during cytokinesis in distinct regions of the cleavage furrow and in the midbody region of mitotic cells. Co-immunoprecipitation experiments revealed this co-localization to be the result of a direct interaction between calretinin and septin 7.

CONCLUSIONS: Our results demonstrate septin 7 not only serving as a "cytoskeletal" protein, but also as a transcription factor repressing calretinin expression. The negative regulation of calretinin by septin 7 and vice versa sheds new light on mechanisms possibly implicated in MM formation and identifies these proteins as transcriptional regulators and putative targets for MM therapy.}, } @article {pmid29698884, year = {2018}, author = {Ismael, H and Cox, S}, title = {Primary intrahepatic mesotheliomas: A case presentation and literature review.}, journal = {International journal of surgery case reports}, volume = {47}, number = {}, pages = {1-6}, pmid = {29698884}, issn = {2210-2612}, abstract = {INTRODUCTION: Primary Intrahepatic mesotheliomas are malignant tumors arising from the mesothelial cell layer covering Glisson's capsule of the liver. They are exceedingly rare with only fourteen cases reported in the literature. They have nonspecific signs and symptoms and need a high index of suspicion and an extensive workup prior to surgery. Surgery remains the mainstay of treatment.

PRESENTATION OF CASE: 48 year old male presented with a 3 months history of abdominal pain, productive cough, anemia and weight loss. He had no history of asbestos exposure. A computed tomography scan and magnetic resonance study demonstrated a heterogeneous subscapular mass within the dome of the right hepatic lobe measuring 11.3 × 6.1 cm involving the diaphragm. Combined resection of the liver and diaphragm was performed to achieve negative margins. Pathology demonstrated an epithelioid necrotic intrahepatic mesothelioma that stained positive for calretinin, CK AE1/AE3, WT-1, D2-40 and CK7.

DISCUSSION: Primary intrahepatic mesotheliomas originate from the mesothelial cells lining Glisson's capsule of the liver. They predominantly invade the liver but may also abut or involve the diaphragm. Surgery should include a diagnostic laparoscopy to rule out occult disease or diffuse peritoneal mesothelioma. Complete resection with negative margins should be attempted while maintaining an adequate future liver remnant. Attempts at dissecting the tumor off the involved diaphragm will result in excessive bleeding and may leave residual disease behind.

CONCLUSION: Intrahepatic mesotheliomas are rare peripherally-located malignant tumors of the liver. They require a high index of suspicion and a comprehensive workup prior to operative intervention.}, } @article {pmid29692597, year = {2018}, author = {Saha, A and Mandal, PK and Manna, A and Khan, K and Pal, S}, title = {Well differentiated papillary mesothelioma of abdomen- a rare case with diagnostic dilemma.}, journal = {Journal of laboratory physicians}, volume = {10}, number = {2}, pages = {248-250}, pmid = {29692597}, issn = {0974-2727}, abstract = {Well-differentiated papillary mesothelioma is a rare tumor occurring predominantly in the peritoneum of young women, a few with history of asbestos exposure. A 28-year-old woman presented with ascites and pain abdomen. Ultrasonography and computed tomography scan of the abdomen revealed a mass in the retroperitoneum measuring 15 cm × 12 cm. Histopathological examination along with immunohistochemistry (IHC) confirmed it to be a papillary mesothelioma in the peritoneum. It is difficult to differentiate from more common malignant mesothelioma and papillary adenocarcinoma, which also have poorer prognosis. The difficulty can be resolved by clinico-radiological correlation along with histopathological examination and IHC.}, } @article {pmid29690982, year = {2018}, author = {Sritharan, SS and Frandsen, JL and Omland, Ø and Bruun, JM}, title = {[Malignant pleural mesothelioma].}, journal = {Ugeskrift for laeger}, volume = {180}, number = {15}, pages = {}, pmid = {29690982}, issn = {1603-6824}, mesh = {Asbestos/adverse effects ; Denmark/epidemiology ; Humans ; *Lung Neoplasms/diagnosis/epidemiology/etiology/therapy ; *Mesothelioma/diagnosis/epidemiology/etiology/therapy ; Mesothelioma, Malignant ; Occupational Exposure/adverse effects ; *Pleural Neoplasms/diagnosis/epidemiology/etiology/therapy ; Prognosis ; Workers' Compensation ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare cancer with a poor prognosis. The disease is of importance, since the incidence in Denmark is increasing despite cessation of the use of asbestos in the 1980s. MPM has a long latency period, and the first symptom is often dyspnoea, typically caused by pleural effusion. The diagnosis is a challenge, because cytology often is non-conclusive, and thoracoscopy is needed to obtain biopsies for immunohistochemistry. The occupational history is important, since the patients are entitled to compensation. The treatment is often limited to palliation.}, } @article {pmid29685095, year = {2018}, author = {Takemura, Y and Satoh, M and Hatanaka, K and Kubota, S}, title = {Zebularine exerts its antiproliferative activity through S phase delay and cell death in human malignant mesothelioma cells.}, journal = {Bioscience, biotechnology, and biochemistry}, volume = {82}, number = {7}, pages = {1159-1164}, doi = {10.1080/09168451.2018.1459466}, pmid = {29685095}, issn = {1347-6947}, mesh = {Apoptosis/*drug effects ; Cell Line, Tumor ; Cell Proliferation/*drug effects ; Cytidine/*analogs & derivatives/pharmacology ; DNA (Cytosine-5-)-Methyltransferase 1/antagonists & inhibitors ; Dose-Response Relationship, Drug ; Fibroblasts/cytology/drug effects ; Glyceraldehyde-3-Phosphate Dehydrogenases/metabolism ; Humans ; Mesothelioma/enzymology/metabolism/*pathology ; S Phase/*drug effects ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {Malignant mesothelioma is an asbestos-related aggressive tumor and current therapy remains ineffective. Zebularine as a DNA methyltransferase (DNMT) inhibitor has an anti-tumor effect in several human cancer cells. The aim of the present study was to investigate whether zebularine could induce antiproliferative effect in human malignant mesothelioma cells. Zebularine induced cell growth inhibition in a dose-dependent manner. In addition, zebularine dose-dependently decreased expression of DNMT1 in all malignant mesothelioma cells tested. Cell cycle analysis indicated that zebularine induced S phase delay. Zebularine also induced cell death in malignant mesothelioma cells. In contrast, zebularine did not induce cell growth inhibition and cell death in human normal fibroblast cells. These results suggest that zebularine has a potential for the treatment of malignant mesothelioma by inhibiting cell growth and inducing cell death.}, } @article {pmid29677456, year = {2019}, author = {Metintas, S and Ak, G and Metintas, M}, title = {A review of the cohorts with environmental and occupational mineral fiber exposure.}, journal = {Archives of environmental & occupational health}, volume = {74}, number = {1-2}, pages = {76-84}, doi = {10.1080/19338244.2018.1467873}, pmid = {29677456}, issn = {2154-4700}, mesh = {Asbestos/*toxicity ; *Environmental Exposure ; Female ; Humans ; Incidence ; Lung Neoplasms/*chemically induced/epidemiology ; Male ; Mesothelioma/*chemically induced/epidemiology ; Mesothelioma, Malignant ; Mineral Fibers/*toxicity ; *Occupational Exposure ; Rural Population ; Zeolites/*toxicity ; }, abstract = {The aim of the study was to examine factors associated with Malignant Mesothelioma (MM) incidence rate of the groups with occupational asbestos and environmental asbestos or erionite exposure in rural area. In this ecological study, a total of 21 cohort datasets (8 environmental and 13 occupational) were evaluated. Data were analyzed using a multiple linear regression analysis model. In environmental cohorts, the risk of MM incidence was higher in women and people exposed to erionite. In this cohort, the incidence rate of MM increased as the median exposure time increased, while the incidence decreased as the median cumulative exposure dose increased. In occupational cohorts, the incidence rate of MM was positively correlated with the median cumulative exposure dose. The risk of mesothelioma was lower in those exposed to tremolite than others. Environmental asbestos exposure is as important as occupational exposure to develop MM, and it has its own unique exposure features on the risk of MM.}, } @article {pmid29669604, year = {2018}, author = {Fennell, DA and Kirkpatrick, E and Cozens, K and Nye, M and Lester, J and Hanna, G and Steele, N and Szlosarek, P and Danson, S and Lord, J and Ottensmeier, C and Barnes, D and Hill, S and Kalevras, M and Maishman, T and Griffiths, G}, title = {CONFIRM: a double-blind, placebo-controlled phase III clinical trial investigating the effect of nivolumab in patients with relapsed mesothelioma: study protocol for a randomised controlled trial.}, journal = {Trials}, volume = {19}, number = {1}, pages = {233}, pmid = {29669604}, issn = {1745-6215}, support = {25352/CRUK_/Cancer Research UK/United Kingdom ; C16728/A21400/CRUK_/Cancer Research UK/United Kingdom ; 15956/CRUK_/Cancer Research UK/United Kingdom ; 21400/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Antineoplastic Agents, Immunological/adverse effects/economics/*therapeutic use ; Clinical Trials, Phase III as Topic ; Cost-Benefit Analysis ; Double-Blind Method ; Drug Costs ; Female ; Humans ; Male ; Mesothelioma/*drug therapy/economics/immunology/pathology ; Multicenter Studies as Topic ; *Neoplasm Recurrence, Local ; Nivolumab/adverse effects/economics/*therapeutic use ; Peritoneal Neoplasms/*drug therapy/economics/immunology/pathology ; Pleural Neoplasms/*drug therapy/economics/immunology/pathology ; Programmed Cell Death 1 Receptor/antagonists & inhibitors/immunology ; Progression-Free Survival ; Quality of Life ; Randomized Controlled Trials as Topic ; Time Factors ; Treatment Outcome ; United Kingdom ; }, abstract = {BACKGROUND: Mesothelioma is an incurable, apoptosis-resistant cancer caused in most cases by previous exposure to asbestos and is increasing in incidence. It represents a growing health burden but remains under-researched, with limited treatment options. Early promising signals of activity relating to both PD-L1- and PD-1-targeted treatment in mesothelioma implicate a dependency of mesothelioma on this immune checkpoint. There is a need to evaluate checkpoint inhibitors in patients with relapsed mesothelioma where treatment options are limited.

METHODS: The addition of 12 months of nivolumab (anti-PD1 antibody) to standard practice will be conducted in the UK using a randomised, placebo-controlled phase III trial (the Cancer Research UK CONFIRM trial). A total of 336 patients with pleural or peritoneal mesothelioma who have received at least two prior lines of therapy will be recruited from UK secondary care sites. Patients will be randomised 2:1 (nivolumab:placebo), stratified according to epithelioid/non-epithelioid, to receive either 240 mg nivolumab monotherapy or saline placebo as a 30-min intravenous infusion. Treatment will be for up to 12 months. We will determine whether the use of nivolumab increases overall survival (the primary efficacy endpoint). Secondary endpoints will include progression-free survival, objective response rate, toxicity, quality of life and cost-effectiveness. Analysis will be performed according to the intention-to-treat principle using a Cox regression analysis for the primary endpoint (and for other time-to-event endpoints).

DISCUSSION: The outcome of this trial will provide evidence of the potential benefit of the use of nivolumab in the treatment of relapsed mesothelioma. If found to be clinically effective, safe and cost-effective it is likely to become the new standard of care in the UK.

TRIAL REGISTRATION: EudraCT Number: 2016-003111-35 (entered on 21 July 2016); ClinicalTrials.gov, ID: NCT03063450 . Registered on 24 February 2017.}, } @article {pmid29666782, year = {2018}, author = {Rossini, M and Rizzo, P and Bononi, I and Clementz, A and Ferrari, R and Martini, F and Tognon, MG}, title = {New Perspectives on Diagnosis and Therapy of Malignant Pleural Mesothelioma.}, journal = {Frontiers in oncology}, volume = {8}, number = {}, pages = {91}, pmid = {29666782}, issn = {2234-943X}, abstract = {Malignant pleural mesothelioma (MPM) is a rare, but severe form of cancer, with an incidence that varies significantly within and among different countries around the world. It develops in about one to two persons per million of the general population, leading to thousands of deaths every year worldwide. To date, the MPM is mostly associated with occupational asbestos exposure. Asbestos represents the predominant etiological factor, with approximately 70% of cases of MPM with well-documented occupational exposure to asbestos, with the exposure time, on average greater than 40 years. Environmental exposure to asbestos is increasingly becoming recognized as a cause of mesothelioma, together with gene mutations. The possible roles of other cofactors, such as viral infection and radiation exposure, are still debated. MPM is a fatal tumor. This cancer arises during its early phase without clinical signs. Consequently, its diagnosis occurs at advanced stages. Standard clinical therapeutic approaches include surgery, chemo- and radiotherapies. Preclinical and clinical researches are making great strides in the field of this deadly disease, identifying new biomarkers and innovative therapeutic approaches. Among the newly identified markers and potential therapeutic targets, circulating microRNAs and the Notch pathway represent promising avenues that could result in the early detection of the tumor and novel therapeutic approaches.}, } @article {pmid29664355, year = {2018}, author = {Caltabiano, R and Loreto, C and Vitale, E and Matera, S and Miozzi, E and Migliore, M and Angelico, G and Tumino, R and Ledda, C and Rapisarda, V}, title = {Fibulin-3 immunoexpression in malignant mesothelioma due to fluoro-edenite: a preliminary report.}, journal = {Future oncology (London, England)}, volume = {14}, number = {6s}, pages = {53-57}, doi = {10.2217/fon-2017-0386}, pmid = {29664355}, issn = {1744-8301}, mesh = {Aged ; Aged, 80 and over ; Asbestos, Amphibole/*toxicity ; Biomarkers, Tumor/metabolism ; Biopsy ; Environmental Exposure/*adverse effects ; Extracellular Matrix Proteins/*metabolism ; Female ; Follow-Up Studies ; Humans ; Incidence ; Lung/pathology ; Lung Neoplasms/chemically induced/epidemiology/*pathology ; Male ; Mesothelioma/chemically induced/epidemiology/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Prognosis ; Retrospective Studies ; Sicily/epidemiology ; }, abstract = {An increased standardized incidence and mortality rate were reported due to malignant mesothelioma (MM) in Biancavilla. Environmental investigations showed the presence of an asbestiform fiber: fluoro-edenite (FE). MM develops with a latency of 20-60 years from exposure and specific and sensitive biomarkers are urgently needed. For this purpose, we evaluated Fibulin-3 (Fb-3) immunoexpression in human cases of MM related to FE exposure and its prognostic role. Immunohistochemical analysis of Fb-3 was carried out in eight MM patients resident in Biancavilla and the analysis showed evidence of environmental exposure to FE fibers. Six MM cases (3 epithelioid and 3 biphasic) showed a high immunoexpression of Fb-3 in neoplastic cells with nuclear and cytoplasmic localization. One epithelioid and one biphasic subtype did not show Fb-3 immunostaining. The results demonstrate the implication of Fb-3 in MM due to FE exposure and may possibly suggest its potential role as a diagnostic and prognostic marker.}, } @article {pmid29664352, year = {2018}, author = {Rapisarda, V and Loreto, C and Castorina, S and Romano, G and Garozzo, SF and Musumeci, A and Migliore, M and Avola, R and Cinà, D and Pomara, C and Ledda, C}, title = {Occupational exposure to fluoro-edenite and prevalence of anti-nuclear autoantibodies.}, journal = {Future oncology (London, England)}, volume = {14}, number = {6s}, pages = {59-62}, doi = {10.2217/fon-2017-0389}, pmid = {29664352}, issn = {1744-8301}, mesh = {Adult ; Antibodies, Antinuclear/*blood/immunology ; Asbestos, Amphibole/*toxicity ; Humans ; Lung/pathology ; Lung Neoplasms/blood/chemically induced/*immunology/mortality ; Male ; Mesothelioma/blood/chemically induced/*immunology/mortality ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/*adverse effects ; Sicily/epidemiology ; Survival Rate ; }, abstract = {An environmental contamination due to an asbestiform mineral fiber, fluoro-edenite (FE), caused a significantly increased mortality rate for malignant mesothelioma in Biancavilla, Italy. Exposure to fluoro-edenite has been associated with inflammatory processes as an early response to inhaled fibers. The aim was to explore prevalence of anti-nuclear autoantibodies (ANA) in a group of construction workers residing and working in the contaminated area. Prevalences for samples positive to ANA were 60% (n = 9) and 13% (n = 2), for exposed and nonexposed, respectively (p-value <0.05), the odds ratio was 9.75 (95% CI: 1.59-59.69). The significance of elevated ANAs in subjects exposed to fibers is unknown; additional studies may provide a better opportunity to establish a correlation between autoimmunity and environmental exposure.}, } @article {pmid29663493, year = {2018}, author = {Munson, P and Lam, YW and MacPherson, M and Beuschel, S and Shukla, A}, title = {Mouse serum exosomal proteomic signature in response to asbestos exposure.}, journal = {Journal of cellular biochemistry}, volume = {119}, number = {7}, pages = {6266-6273}, pmid = {29663493}, issn = {1097-4644}, support = {P20 GM103449/GM/NIGMS NIH HHS/United States ; R01 ES021110/ES/NIEHS NIH HHS/United States ; }, mesh = {Administration, Oral ; Animals ; Asbestos/administration & dosage/*toxicity ; Blood Proteins/drug effects/*metabolism ; Carcinogens/administration & dosage/*toxicity ; Exosomes/drug effects/*metabolism ; Mice ; Mice, Inbred C57BL ; Proteomics ; Respiratory Aspiration ; }, abstract = {Asbestos-induced diseases like fibrosis and mesothelioma are very aggressive, without any treatment options. These diseases are diagnosed only at the terminal stages due to lack of early stage biomarkers. The recent discovery of exosomes as circulating biomarkers led us to look for exosomal biomarkers of asbestos exposure in mouse blood. In our model, mice were exposed to asbestos as a single bolus dose by oropharyngeal aspiration. Fifty-six days later blood was collected, exosomes were isolated from plasma and characterized and subjected to proteomic analysis using Tandem Mass Tag labeling. We identified many proteins, some of which were more abundant in asbestos exposed mouse serum exosomes, and three selected proteins were validated by immunoblotting. Our study is the first to show that serum exosomal proteomic signatures can reveal some important proteins relevant to asbestos exposure that have the potential to be validated as candidate biomarkers. We hope to extrapolate the positive findings of this study to humans in future studies.}, } @article {pmid29659015, year = {2018}, author = {Barbarino, M and Cesari, D and Intruglio, R and Indovina, P and Namagerdi, A and Bertolino, FM and Bottaro, M and Rahmani, D and Bellan, C and Giordano, A}, title = {Possible repurposing of pyrvinium pamoate for the treatment of mesothelioma: A pre-clinical assessment.}, journal = {Journal of cellular physiology}, volume = {233}, number = {9}, pages = {7391-7401}, doi = {10.1002/jcp.26579}, pmid = {29659015}, issn = {1097-4652}, mesh = {Cell Line, Tumor ; Cell Movement/drug effects/genetics ; Cell Proliferation/drug effects ; Dose-Response Relationship, Drug ; Down-Regulation/drug effects ; *Drug Repositioning ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Inhibitory Concentration 50 ; Mesothelioma/*drug therapy/genetics/pathology ; Pyrvinium Compounds/pharmacology/*therapeutic use ; RNA, Messenger/genetics/metabolism ; Spheroids, Cellular/drug effects/metabolism/pathology ; Time Factors ; Wnt Signaling Pathway/drug effects/genetics ; beta Catenin/metabolism ; }, abstract = {Malignant mesothelioma (MM) is a very aggressive asbestos-related cancer, whose incidence is increasing worldwide. Unfortunately, no effective therapies are currently available and the prognosis is extremely poor. Recently, the anti-helminthic drug pyrvinium pamoate has attracted a strong interest for its anti-cancer activity, which has been demonstrated in many cancer models. Considering the previously established inhibitory effect of pyrvinium pamoate on the Wnt/β-catenin pathway and given the important role of this pathway in MM, we investigated the potential anti-tumor activity of this drug in MM cell lines. We observed that pyrvinium pamoate significantly impairs MM cell proliferation, cloning efficiency, migration, and tumor spheroid formation. At the molecular level, our data show that pyrvinium pamoate down-regulates the expression of β-catenin and Wnt-regulates genes. Overall, our study suggests that the repurposing of pyrvinium pamoate for MM treatment could represent a new promising therapeutic approach.}, } @article {pmid29656754, year = {2018}, author = {Sneddon, S and Dick, I and Lee, YCG and Musk, AWB and Patch, AM and Pearson, JV and Waddell, N and Allcock, RJN and Holt, RA and Robinson, BWS and Creaney, J}, title = {Malignant cells from pleural fluids in malignant mesothelioma patients reveal novel mutations.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {119}, number = {}, pages = {64-70}, doi = {10.1016/j.lungcan.2018.03.009}, pmid = {29656754}, issn = {1872-8332}, mesh = {Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Cyclin-Dependent Kinase Inhibitor p16/*genetics ; DNA Copy Number Variations ; Environmental Exposure/adverse effects ; Female ; Humans ; Lung Neoplasms/*genetics/pathology ; Male ; Mesothelioma/*genetics/pathology ; Mesothelioma, Malignant ; Middle Aged ; Mutation/*genetics ; Neurofibromin 2/*genetics ; Pleural Effusion, Malignant/*genetics/pathology ; Tumor Cells, Cultured ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {OBJECTIVES: Malignant mesothelioma (MM) is an asbestos related tumour affecting cells of serosal cavities. More than 70% of MM patients develop pleural effusions which contain tumour cells, representing a readily accessible source of malignant cells for genetic analysis. Although common somatic mutations and losses have been identified in solid MM tumours, the characterization of tumour cells within pleural effusions could provide novel insights but is little studied.

MATERIALS AND METHODS: DNA and RNA were extracted from cells from short term cultures of 27 human MM pleural effusion samples. Whole exome and transcriptome sequencing was performed using the Ion Torrent platform. Somatic mutations were identified using VarScan2 and SomaticSniper. Copy number alterations were identified using ExomeCNV in R. Significant copy number alterations were identified across all samples using GISTIC2.0. The association between tumour intrinsic properties and survival was analyzed using the Cox proportional hazards regression model.

RESULTS: We identified BAP1, CDKN2A and NF2 alterations in the cells from MM pleural effusions at a higher frequency than what is typically seen in MM tumours from surgical series. The median mutation rate was 1.09 mutations/Mb. TRAF7 and LATS2 alterations were also identified at a high frequency (66% and 59% respectively). Novel regions of interest were identified, including alterations in FGFR3, and the regions 19p13.3, 8p23.1 and 1p36.32.

CONCLUSION: Short term cultures of tumour cells from MM pleural effusions offer an accessible alternative to surgical tumour biopsies in the study of MM genomics and reveal novel mutations of interest. Pleural effusion tumour cells provide an opportunity for the monitoring of tumour dynamics, treatment response and the clonal evolution of MM tumours.}, } @article {pmid29651248, year = {2018}, author = {Sinis, SI and Hatzoglou, C and Gourgoulianis, KI and Zarogiannis, SG}, title = {Carbon Nanotubes and Other Engineered Nanoparticles Induced Pathophysiology on Mesothelial Cells and Mesothelial Membranes.}, journal = {Frontiers in physiology}, volume = {9}, number = {}, pages = {295}, pmid = {29651248}, issn = {1664-042X}, abstract = {Nanoparticles have great potential for numerous applications due to their unique physicochemical properties. However, concerns have been raised that they may induce deleterious effects on biological systems. There is accumulating evidence that, like asbestos, inhaled nanomaterials of >5 μm and high aspect ratio (3:1), particularly rod-like carbon nanotubes, may inflict pleural disease including mesothelioma. Additionally, a recent set of case reports suggests that inhalation of polyacrylate/nanosilica could in part be associated with inflammation and fibrosis of the pleura of factory workers. However, the adverse outcomes of nanoparticle exposure to mesothelial tissues are still largely unexplored. In that context, the present review aims to provide an overview of the relevant pathophysiological implications involving toxicological studies describing effects of engineered nanoparticles on mesothelial cells and membranes. In vitro studies primarily emphasize on simulating cellular uptake and toxicity of nanotubes on benign or malignant cell lines. On the other hand, in vivo studies focus on illustrating endpoints of serosal pathology in rodent animal models. From a molecular aspect, some nanoparticle categories are shown to be cytotoxic and genotoxic after acute treatment, whereas chronic incubation may lead to malignant-like transformation. At an organism level, a number of fibrous shaped nanotubes are related with features of chronic inflammation and MWCNT-7 is the only type to consistently inflict mesothelioma.}, } @article {pmid29641489, year = {2018}, author = {Felley-Bosco, E and Rehrauer, H}, title = {Non-Coding Transcript Heterogeneity in Mesothelioma: Insights from Asbestos-Exposed Mice.}, journal = {International journal of molecular sciences}, volume = {19}, number = {4}, pages = {}, pmid = {29641489}, issn = {1422-0067}, mesh = {Animals ; Asbestos/toxicity ; *Genetic Heterogeneity ; Mesothelioma/etiology/*genetics ; Mice ; RNA, Untranslated/*genetics ; Transcriptome ; }, abstract = {Mesothelioma is an aggressive, rapidly fatal cancer and a better understanding of its molecular heterogeneity may help with making more efficient therapeutic strategies. Non-coding RNAs represent a larger part of the transcriptome but their contribution to diseases is not fully understood yet. We used recently obtained RNA-seq data from asbestos-exposed mice and performed data mining of publicly available datasets in order to evaluate how non-coding RNA contribute to mesothelioma heterogeneity. Nine non-coding RNAs are specifically elevated in mesothelioma tumors and contribute to human mesothelioma heterogeneity. Because some of them have known oncogenic properties, this study supports the concept of non-coding RNAs as cancer progenitor genes.}, } @article {pmid29635378, year = {2018}, author = {Schelch, K and Wagner, C and Hager, S and Pirker, C and Siess, K and Lang, E and Lin, R and Kirschner, MB and Mohr, T and Brcic, L and Marian, B and Holzmann, K and Grasl-Kraupp, B and Krupitza, G and Laszlo, V and Klikovits, T and Dome, B and Hegedus, B and Garay, T and Reid, G and van Zandwijk, N and Klepetko, W and Berger, W and Grusch, M and Hoda, MA}, title = {FGF2 and EGF induce epithelial-mesenchymal transition in malignant pleural mesothelioma cells via a MAPKinase/MMP1 signal.}, journal = {Carcinogenesis}, volume = {39}, number = {4}, pages = {534-545}, doi = {10.1093/carcin/bgy018}, pmid = {29635378}, issn = {1460-2180}, mesh = {Cell Line, Tumor ; Epidermal Growth Factor/*metabolism ; Epithelial-Mesenchymal Transition/*physiology ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Fibroblast Growth Factor 2/*metabolism ; Humans ; Lung Neoplasms/metabolism/*pathology ; Matrix Metalloproteinase 1/metabolism ; Mesothelioma/metabolism/*pathology ; Mesothelioma, Malignant ; Pleural Neoplasms/metabolism/*pathology ; Signal Transduction/physiology ; }, abstract = {Malignant pleural mesothelioma (MPM), an aggressive malignancy affecting pleural surfaces, occurs in three main histological subtypes. The epithelioid and sarcomatoid subtypes are characterized by cuboid and fibroblastoid cells, respectively. The biphasic subtype contains a mixture of both. The sarcomatoid subtype expresses markers of epithelial-mesenchymal transition (EMT) and confers the worst prognosis, but the signals and pathways controlling EMT in MPM are not well understood. We demonstrate that treatment with FGF2 or EGF induced a fibroblastoid morphology in several cell lines from biphasic MPM, accompanied by scattering, decreased cell adhesion and increased invasiveness. This depended on the MAP-kinase pathway but was independent of TGFβ or PI3-kinase signaling. In addition to changes in known EMT markers, microarray analysis demonstrated differential expression of MMP1, ESM1, ETV4, PDL1 and BDKR2B in response to both growth factors and in epithelioid versus sarcomatoid MPM. Inhibition of MMP1 prevented FGF2-induced scattering and invasiveness. Moreover, in MPM cells with sarcomatoid morphology, inhibition of FGF/MAP-kinase signaling induced a more epithelioid morphology and gene expression pattern. Our findings suggest a critical role of the MAP-kinase axis in the morphological and behavioral plasticity of mesothelioma.}, } @article {pmid29616141, year = {2018}, author = {de Fonseka, D and Underwood, W and Stadon, L and Rahman, N and Edey, A and Rogers, C and Maskell, NA}, title = {Randomised controlled trial to compare the diagnostic yield of positron emission tomography CT (PET-CT) TARGETed pleural biopsy versus CT-guided pleural biopsy in suspected pleural malignancy (TARGET trial).}, journal = {BMJ open respiratory research}, volume = {5}, number = {1}, pages = {e000270}, pmid = {29616141}, issn = {2052-4439}, support = {PB-PG-0214-33095/DH_/Department of Health/United Kingdom ; }, abstract = {INTRODUCTION: Pleural malignancy, particularly malignant pleural mesothelioma (MPM) is increasing in incidence due to the long latency period from exposure to asbestos to development of the disease. MPM can be challenging to diagnose. For patients presenting without a pleural effusion, CT-guided biopsy remains the primary choice of biopsy, but the diagnostic sensitivity of this investigation is 70%-75%. Therefore, a proportion of patients will go on to require further biopsies. If the first biopsy is non-diagnostic, the chances of further non-diagnostic biopsies are high in MPM.

METHODS: Target is a multicentre randomised controlled trial, aiming to recruit 78 patients over a 30-month period, from 10 centres in the UK. Patients will be randomised to either the standard arm which is a second CT-guided biopsy, or the interventional arm, a positron emission tomography-CT scan followed by a targeted CT-guided biopsy. Patients will be followed up for 12 months (patients recruited in the last 6 months of recruitment will have 6 months of follow-up). MPM biomarker mesothelin will be checked at baseline, 6 month and 12 month follow-up appointments where patients are able to attend these appointments.

ETHICS AND DISSEMINATION: Ethical approval for this trial was granted by the South West-Exeter research and ethics committee (reference number 15/SW/0156). Results of the trial will be published in a peer-reviewed journal and presented at an international conference.

TRIAL REGISTRATION NUMBER: ISRCTN 14024829; Pre-results.}, } @article {pmid29608538, year = {2018}, author = {Liu, Y and Marsh, GM and Roggli, VL}, title = {Asbestos Fiber Concentrations in the Lungs of Brake Repair Workers: An Updated Analysis Using Several Regression Methods to Handle Nondetectable Measurements.}, journal = {Journal of occupational and environmental medicine}, volume = {60}, number = {7}, pages = {661-671}, doi = {10.1097/JOM.0000000000001320}, pmid = {29608538}, issn = {1536-5948}, mesh = {Adult ; Aged ; Asbestos, Amphibole/*analysis/toxicity ; *Automobiles ; Humans ; Limit of Detection ; Lung/*chemistry ; Maintenance ; Mesothelioma/*etiology ; Middle Aged ; Occupational Diseases/*etiology ; Occupational Exposure/adverse effects/analysis/*statistics & numerical data ; Peritoneal Neoplasms/*etiology ; Pleural Neoplasms/*etiology ; Regression Analysis ; }, abstract = {OBJECTIVES: The aim of the study was to reanalyze an updated database of lung asbestos fiber levels for 21 brake repair workers who died of mesothelioma using robust maximum likelihood-based regression methods to address nondetectable measurements.

METHODS: We applied bivariate normal regression to address the doubly left-censored situation where both the lung fiber concentration of noncommercial (TAA) and commercial amphiboles (AC) were subject to detection limits. For the single left-censored situation, we applied censored normal regression to study the relationship between duration of employment (DOE) and TAA.

RESULTS: We found a statistically significant positive relationship between TAA and AC (β = 0.49, 95% confidence interval [CI], 0.11 to 0.86) and a not statistically significant relationship between DOE and TAA (β = 0.02, 95% CI, -0.03 to 0.06).

CONCLUSIONS: Our results provide additional support for the conclusion that exposure to commercial amphibole asbestos, and not chrysotile, is related to the occurrence of mesothelioma among some brake workers.}, } @article {pmid29587685, year = {2018}, author = {Nagamatsu, Y and Oze, I and Aoe, K and Hotta, K and Kato, K and Nakagawa, J and Hara, K and Kishimoto, T and Fujimoto, N}, title = {Quality of life of survivors of malignant pleural mesothelioma in Japan: a cross sectional study.}, journal = {BMC cancer}, volume = {18}, number = {1}, pages = {350}, pmid = {29587685}, issn = {1471-2407}, mesh = {Adult ; Aged ; Aged, 80 and over ; Cross-Sectional Studies ; Female ; Humans ; Japan/epidemiology ; Lung Neoplasms/*epidemiology/therapy ; Male ; Mesothelioma/*epidemiology/therapy ; Mesothelioma, Malignant ; Middle Aged ; Palliative Care ; Pleural Neoplasms/*epidemiology/therapy ; *Quality of Life ; Surveys and Questionnaires ; *Survivors ; }, abstract = {BACKGROUND: Previous studies have indicated that people with malignant pleural mesothelioma (MPM) have a poor quality of life (QOL); however, information about the QOL of people with MPM in Japan is anecdotal. The aims of this study were to investigate the QOL of survivors of MPM in Japan and to determine the factors that correlate with their QOL.

METHODS: This was a cross sectional study. The included patients were those diagnosed with MPM in Japan. We created a self-administered questionnaire consisting of 64 questions. The questionnaires were sent to hospitals and patient advocacy groups, distributed to the patients, completed, and sent back to the researchers by postal mail. QOL was assessed with the European Organization for Research and Treatment of Cancer 16 questionnaire (QLQ) and the short version of the core domains of the Comprehensive Quality of Life Outcome questionnaire (CoQoLo).

RESULTS: In total, 133 questionnaires were collected. The QLQ assessments demonstrated that the survivors of MPM most frequently complained of fatigue, pain, sleep disturbances, and dyspnea. The symptom scales were acceptable, but the functional scales were significantly poorer for the patients with poor performance statuses (PSs). The short CoQoLo assessment was very unfavorable for 'Being free from physical pain.' Being a long-term survivor and a survivor with a poor PS were significantly correlated with poor global health status.

CONCLUSIONS: Survivors of MPM have impaired function, a variety of symptoms, and lower QOL. Survivors of MPM, even those in good physical condition, need broad support.}, } @article {pmid29587439, year = {2018}, author = {Sato, T and Sekido, Y}, title = {NF2/Merlin Inactivation and Potential Therapeutic Targets in Mesothelioma.}, journal = {International journal of molecular sciences}, volume = {19}, number = {4}, pages = {}, pmid = {29587439}, issn = {1422-0067}, mesh = {Actins/metabolism ; Antineoplastic Agents/pharmacology/therapeutic use ; Gene Expression Regulation, Neoplastic/drug effects ; *Genetic Variation ; Hippo Signaling Pathway ; Humans ; Lung Neoplasms/drug therapy/*genetics/metabolism ; Mesothelioma/drug therapy/*genetics/metabolism ; Mesothelioma, Malignant ; Neurofibromin 2/*genetics/metabolism ; Protein Serine-Threonine Kinases/metabolism ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism ; }, abstract = {The neurofibromatosis type 2 (NF2) gene encodes merlin, a tumor suppressor protein frequently inactivated in schwannoma, meningioma, and malignant mesothelioma (MM). The sequence of merlin is similar to that of ezrin/radixin/moesin (ERM) proteins which crosslink actin with the plasma membrane, suggesting that merlin plays a role in transducing extracellular signals to the actin cytoskeleton. Merlin adopts a distinct closed conformation defined by specific intramolecular interactions and regulates diverse cellular events such as transcription, translation, ubiquitination, and miRNA biosynthesis, many of which are mediated through Hippo and mTOR signaling, which are known to be closely involved in cancer development. MM is a very aggressive tumor associated with asbestos exposure, and genetic alterations in NF2 that abrogate merlin's functional activity are found in about 40% of MMs, indicating the importance of NF2 inactivation in MM development and progression. In this review, we summarize the current knowledge of molecular events triggered by NF2/merlin inactivation, which lead to the development of mesothelioma and other cancers, and discuss potential therapeutic targets in merlin-deficient mesotheliomas.}, } @article {pmid29580185, year = {2018}, author = {Beaucham, C and King, B and Feldmann, K and Harper, M and Dozier, A}, title = {Assessing occupational erionite and respirable crystalline silica exposure among outdoor workers in Wyoming, South Dakota, and Montana.}, journal = {Journal of occupational and environmental hygiene}, volume = {15}, number = {6}, pages = {455-465}, doi = {10.1080/15459624.2018.1447116}, pmid = {29580185}, issn = {1545-9632}, mesh = {Construction Industry ; Forestry ; Humans ; Inhalation Exposure/analysis ; Montana ; National Institute for Occupational Safety and Health, U.S. ; Occupational Exposure/*analysis/prevention & control ; Particulate Matter/analysis ; Silicon Dioxide/*analysis ; South Dakota ; United States ; Wyoming ; Zeolites/*analysis ; }, abstract = {Erionite is a naturally occurring fibrous mineral found in many parts of the world, including the western United States. Inhalational exposure to erionite fibers in some localities is associated with health effects similar to those caused by asbestos exposure, including malignant mesothelioma. Therefore, there is concern regarding occupational exposures in the western United States. Currently, there are no standard sampling and analytical methods for airborne erionite fibers, as well as no established occupational exposure limits. Due to the potential adverse health effects, characterizing and minimizing exposures is prudent. Crystalline silica also occurs naturally in areas where erionite is found, principally as the mineral quartz. Work activities involving rocks containing quartz and soils derived from those rocks can lead to exposure to respirable crystalline silica (RCS). The typically dry and dusty environment of the western United States can increase the likelihood of exposures to aerosolized rocks and soils, but inhalation exposure is also possible in more humid conditions. In this case study, we describe several outdoor occupational environments with potential exposures to erionite and RCS. We describe our method for evaluating those exposures and demonstrate: (1) the occurrence of occupational exposures to airborne erionite and RCS, (2) that the chemical make-up of the erionite mineral can be determined, and (3) that effective dust control practices are needed to reduce employee exposures to these minerals.}, } @article {pmid29577057, year = {2018}, author = {Field, Z and Zori, A and Khullar, V and Mota, M and Feely, M and Firpi, RJ}, title = {Malignant Peritoneal Mesothelioma Presenting as Mucinous Ascites.}, journal = {ACG case reports journal}, volume = {5}, number = {}, pages = {e23}, pmid = {29577057}, issn = {2326-3253}, abstract = {We present a rare case of a 46-year-old man presenting with mucinous ascites secondary to malignant peritoneal mesothelioma (MPM) that was diagnosed via colonoscopy with biopsies. Both our findings and the clinical presentation were unique. While it is widely known that asbestos exposure is commonly associated with pleural mesothelioma, 6-10% of malignant mesotheliomas arise from the peritoneum. To date, only 4 cases of MPM with the primary tumor site in the colon have been described in the literature.}, } @article {pmid29575036, year = {2018}, author = {Bonafede, M and Ghelli, M and Corfiati, M and Rosa, V and Guglielmucci, F and Granieri, A and Branchi, C and Iavicoli, S and Marinaccio, A}, title = {The psychological distress and care needs of mesothelioma patients and asbestos-exposed subjects: A systematic review of published studies.}, journal = {American journal of industrial medicine}, volume = {61}, number = {5}, pages = {400-412}, doi = {10.1002/ajim.22831}, pmid = {29575036}, issn = {1097-0274}, mesh = {Adaptation, Psychological ; Asbestos/*adverse effects ; Depression/psychology ; Female ; Humans ; Lung Neoplasms/epidemiology/*psychology ; Male ; Mesothelioma/epidemiology/*psychology ; Mesothelioma, Malignant ; Occupational Exposure/*adverse effects ; Quality of Life ; Social Support ; *Stress, Psychological ; }, abstract = {BACKGROUND: The purpose of this study is to present the results of a systematic review of published research that focuses on psychological aspects of malignant mesothelioma patients and asbestos-exposed people.

METHODS: Our research includes primary studies published between 1980 and 2016, using information from the Cochrane Library, the Psychology Behavioral Sciences Collection, PsychINFO, PubMed, PubGet, PubPsych, and Scopus, in compliance with PRISMA guidelines.

RESULTS: We identified 12 papers that investigated the psychological distress and care needs of mesothelioma patients, and nine papers for asbestos-exposed subjects.

CONCLUSIONS: This paper highlights the paucity of studies on the psychological distress and care needs of mesothelioma patients and asbestos-exposed subjects. It confirms that malignant mesothelioma is associated with the physical, emotional, and social functioning of patients, while also suggesting that the risk of developing asbestos-related diseases among asbestos-exposed subjects is associated with high levels of psychological distress, despair, and mental health difficulties.}, } @article {pmid29574645, year = {2018}, author = {Vimercati, L and Cavone, D and Lovreglio, P and De Maria, L and Caputi, A and Ferri, GM and Serio, G}, title = {Environmental asbestos exposure and mesothelioma cases in Bari, Apulia region, southern Italy: a national interest site for land reclamation.}, journal = {Environmental science and pollution research international}, volume = {25}, number = {16}, pages = {15692-15701}, pmid = {29574645}, issn = {1614-7499}, mesh = {Aged ; Antineoplastic Agents/therapeutic use ; Asbestos/*toxicity ; Carcinogens, Environmental/*toxicity ; Cities ; *Environmental Exposure ; Fatal Outcome ; Female ; Humans ; Italy ; Lung Neoplasms/chemically induced/diagnosis/*drug therapy/*surgery ; Male ; Mesothelioma/chemically induced/diagnosis/*drug therapy/*surgery ; Mesothelioma, Malignant ; Middle Aged ; Treatment Outcome ; }, abstract = {Asbestos is an environmental carcinogen, and asbestos-related diseases are a global-scale public health issue. We report three cases (one male and two females) of pleural malignant mesothelioma (PMM) caused by environmental asbestos exposure reported by the Apulia Regional Operating Centre (COR) to the National Mesothelioma Registry (ReNaM). The patients revealed no history of asbestos exposure even after detailed assessment. The environmental (neighborhood) asbestos exposure for each of the three cases was due to both the residential history of the subjects and their workplace, close to a military barracks, at a distance of between 45 and 100 m. Moreover, in addition to this new source of pollution, an asbestos cement factory was located in the urban area of Bari municipality, in the Apulia region, southern Italy. Environmental-residential/neighborhood asbestos exposure in the city of Bari, a contaminated area classified as a site of national concern for land reclamation, is discussed also with reference to the military barracks.}, } @article {pmid29574404, year = {2018}, author = {Marsh, GM and Riordan, AS and Keeton, KA and Benson, SM}, title = {Response to: 'Reanalysis of non-occupational exposure to asbestos and the risk of pleural mesothelioma' by Finkelstein.}, journal = {Occupational and environmental medicine}, volume = {75}, number = {6}, pages = {473-474}, doi = {10.1136/oemed-2018-105020}, pmid = {29574404}, issn = {1470-7926}, mesh = {*Asbestos ; Humans ; *Lung Neoplasms ; *Mesothelioma ; *Pleural Neoplasms ; }, } @article {pmid29572002, year = {2018}, author = {Tsim, S and Humphreys, CA and Cowell, GW and Stobo, DB and Noble, C and Woodward, R and Kelly, CA and Alexander, L and Foster, JE and Dick, C and Blyth, KG}, title = {Early Contrast Enhancement: A novel magnetic resonance imaging biomarker of pleural malignancy.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {118}, number = {}, pages = {48-56}, pmid = {29572002}, issn = {1872-8332}, support = {25355/CRUK_/Cancer Research UK/United Kingdom ; ETM/285/CSO_/Chief Scientist Office/United Kingdom ; }, mesh = {Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Biomarkers, Tumor ; Contrast Media ; Environmental Exposure/adverse effects ; Female ; Humans ; Lung Neoplasms/*diagnosis/pathology ; Magnetic Resonance Imaging/*methods ; Male ; Mesothelioma/*diagnosis/pathology ; Mesothelioma, Malignant ; Pleura/diagnostic imaging/*pathology ; Pleural Neoplasms/*diagnosis/pathology ; Predictive Value of Tests ; Prognosis ; Prospective Studies ; Sensitivity and Specificity ; }, abstract = {INTRODUCTION: Pleural Malignancy (PM) is often occult on subjective radiological assessment. We sought to define a novel, semi-objective Magnetic Resonance Imaging (MRI) biomarker of PM, targeted to increased tumour microvessel density (MVD) and applicable to minimal pleural thickening.

MATERIALS AND METHODS: 60 consecutive patients with suspected PM underwent contrast-enhanced 3-T MRI then pleural biopsy. In 58/60, parietal pleura signal intensity (SI) was measured in multiple regions of interest (ROI) at multiple time-points, generating ROI SI/time curves and Mean SI gradient (MSIG: SI increment/time). The diagnostic performance of Early Contrast Enhancement (ECE; which was defined as a SI peak in at least one ROI at or before 4.5 min) was compared with subjective MRI and Computed Tomography (CT) morphology results. MSIG was correlated against tumour MVD (based on Factor VIII immunostain) in 31 patients with Mesothelioma.

RESULTS: 71% (41/58) patients had PM. Pleural thickening was <10 mm in 49/58 (84%). ECE sensitivity was 83% (95% CI 61-94%), specificity 83% (95% CI 68-91%), positive predictive value 68% (95% CI 47-84%), negative predictive value 92% (78-97%). ECE performance was similar or superior to subjective CT and MRI. MSIG correlated with MVD (r = 0.4258, p = .02).

DISCUSSION: ECE is a semi-objective, perfusion-based biomarker of PM, measurable in minimal pleural thickening. Further studies are warranted.}, } @article {pmid29571785, year = {2018}, author = {Kato, K and Gemba, K and Ashizawa, K and Arakawa, H and Honda, S and Noguchi, N and Honda, S and Fujimoto, N and Kishimoto, T}, title = {Low-dose chest computed tomography screening of subjects exposed to asbestos.}, journal = {European journal of radiology}, volume = {101}, number = {}, pages = {124-128}, doi = {10.1016/j.ejrad.2018.02.017}, pmid = {29571785}, issn = {1872-7727}, mesh = {Aged ; Aged, 80 and over ; *Asbestos ; Cross-Sectional Studies ; Female ; Humans ; Lung/diagnostic imaging/pathology ; Lung Neoplasms/*diagnostic imaging/*epidemiology/pathology ; Male ; Mesothelioma/diagnostic imaging/epidemiology/pathology ; Mesothelioma, Malignant ; Middle Aged ; Prevalence ; Prospective Studies ; *Radiation Dosage ; Tomography, X-Ray Computed/*methods ; }, abstract = {OBJECTIVES: The primary aim was to reveal the prevalence of lung cancer (LC) and malignant pleural mesothelioma (MPM) in subjects with past asbestos exposure (AE). We also examined pulmonary or pleural changes correlated with the development of LC.

MATERIALS AND METHODS: This was a prospective, multicenter, cross-sectional study. There were 2132 subjects enrolled between 2010 and 2012. They included 96.2% men and 3.8% women, with a mean age of 76.1 years; 78.8% former or current smokers; and 21.2% never smokers. We screened subjects using low-dose computed tomography (CT). The CT images were taken with a CT dose Index of 2.7 mGy. The evaluated CT findings included subpleural curvilinear shadow/subpleural dots, ground glass opacity or interlobular reticular opacity, traction bronchiectasia, honeycombing change, parenchymal band, emphysema changes, pleural effusion, diffuse pleural thickening, rounded atelectasis, pleural plaques (PQs), and tumor formation.

RESULTS: The PQs were detected in most of subjects (89.4%) and emphysema changes were seen in 46.0%. Fibrotic changes were detected in 565 cases (26.5%). A pathological diagnosis of LC was confirmed in 45 cases (2.1%) and MPM was confirmed in 7 cases (0.3%). The prevalence of LC was 2.5% in patients with a smoking history, which was significantly higher than that in never smokers (0.7%, p = 0.027). The prevalence of LC was 2.8% in subjects with emphysema changes, which was higher than that of subjects without those findings (1.6%); although, the difference was not statistically significant (p = 0.056). The prevalence of LC in subjects with both fibrotic plus emphysema changes was 4.0%, which was significantly higher than that of subjects with neither of those findings (1.8%, p = 0.011). Logistic regression analysis revealed smoking history, fibrotic plus emphysema changes, and pleural effusion as significant explanatory variables.

CONCLUSIONS: Smoking history, fibrotic plus emphysema changes, and pleural effusion were correlated with the prevalence of LC.}, } @article {pmid29564943, year = {2018}, author = {Maxim, LD and Utell, MJ}, title = {Review of refractory ceramic fiber (RCF) toxicity, epidemiology and occupational exposure.}, journal = {Inhalation toxicology}, volume = {30}, number = {2}, pages = {49-71}, doi = {10.1080/08958378.2018.1448019}, pmid = {29564943}, issn = {1091-7691}, mesh = {Air Pollutants, Occupational/*toxicity ; Animals ; Environmental Monitoring ; Humans ; Mineral Fibers/*toxicity ; Occupational Diseases/*epidemiology ; Occupational Exposure/adverse effects/analysis ; }, abstract = {This literature review on refractory ceramic fibers (RCF) summarizes relevant information on manufacturing, processing, applications, occupational exposure, toxicology and epidemiology studies. Rodent toxicology studies conducted in the 1980s showed that RCF caused fibrosis, lung cancer and mesothelioma. Interpretation of these studies was difficult for various reasons (e.g. overload in chronic inhalation bioassays), but spurred the development of a comprehensive product stewardship program under EPA and later OSHA oversight. Epidemiology studies (both morbidity and mortality) were undertaken to learn more about possible health effects resulting from occupational exposure. No chronic animal bioassay studies on RCF have been conducted since the 1980s. The results of the ongoing epidemiology studies confirm that occupational exposure to RCF is associated with the development of pleural plaques and minor decrements in lung function, but no interstitial fibrosis or incremental lung cancer. Evidence supporting a finding that urinary tumors are associated with RCF exposure remains, but is weaker. One reported, but unconfirmed, mesothelioma was found in an individual with prior occupational asbestos exposure. An elevated SMR for leukemia was found, but was absent in the highly exposed group and has not been observed in studies of other mineral fibers. The industry will continue the product stewardship program including the mortality study.}, } @article {pmid29553831, year = {2018}, author = {Munson, P and Lam, YW and Dragon, J and MacPherson, M and Shukla, A}, title = {Exosomes from asbestos-exposed cells modulate gene expression in mesothelial cells.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {32}, number = {8}, pages = {4328-4342}, pmid = {29553831}, issn = {1530-6860}, support = {P20 GM103449/GM/NIGMS NIH HHS/United States ; P20 RR021905/RR/NCRR NIH HHS/United States ; P30 GM118228/GM/NIGMS NIH HHS/United States ; R01 ES021110/ES/NIEHS NIH HHS/United States ; }, mesh = {Asbestos/*toxicity ; Carcinogens/toxicity ; Cell Line ; Epithelial Cells/drug effects/*physiology ; Epithelial-Mesenchymal Transition/drug effects/physiology ; Epithelium/drug effects/*physiology ; Exosomes/*genetics ; Gene Expression/drug effects/*genetics ; Humans ; Inhalation Exposure/adverse effects ; Lung/drug effects/*physiology ; Macrophages/drug effects/physiology ; }, abstract = {Asbestos exposure is a determinate cause of many diseases, such as mesothelioma, fibrosis, and lung cancer, and poses a major human health hazard. At this time, there are no identified biomarkers to demarcate asbestos exposure before the presentation of disease and symptoms, and there is only limited understanding of the underlying biology that governs asbestos-induced disease. In our study, we used exosomes, 30-140 nm extracellular vesicles, to gain insight into these knowledge gaps. As inhaled asbestos is first encountered by lung epithelial cells and macrophages, we hypothesize that asbestos-exposed cells secrete exosomes with signature proteomic cargo that can alter the gene expression of mesothelial cells, contributing to disease outcomes like mesothelioma. In the present study using lung epithelial cells (BEAS2B) and macrophages (THP-1), we first show that asbestos exposure causes changes in abundance of some proteins in the exosomes secreted from these cells. Furthermore, exposure of human mesothelial cells (HPM3) to these exosomes resulted in gene expression changes related to epithelial-to-mesenchymal transition and other cancer-related genes. This is the first report to indicate that asbestos-exposed cells secrete exosomes with differentially abundant proteins and that those exosomes have a gene-altering effect on mesothelial cells.-Munson, P., Lam, Y.-W., Dragon, J. MacPherson, M., Shukla, A. Exosomes from asbestos-exposed cells modulate gene expression in mesothelial cells.}, } @article {pmid29547510, year = {2018}, author = {Allen, LP and Baez, J and Stern, MEC and Takahashi, K and George, F}, title = {Trends and the Economic Effect of Asbestos Bans and Decline in Asbestos Consumption and Production Worldwide.}, journal = {International journal of environmental research and public health}, volume = {15}, number = {3}, pages = {}, pmid = {29547510}, issn = {1660-4601}, support = {001/WHO_/World Health Organization/International ; }, mesh = {*Asbestos/economics/toxicity ; Environmental Exposure/*prevention & control ; Gross Domestic Product ; Humans ; }, abstract = {Although some countries have reduced asbestos consumption and instituted bans, other countries continue to produce and consume asbestos even as asbestos-related deaths mount and the associated societal costs are high. Asbestos production and consumption has declined globally; the number of bans has increased; and the speed at which countries have tapered off consumption has increased. Using country-level data, we study the economic impact of historical changes in the production and use of asbestos. We compare changes in gross domestic product (GDP) following the enactment of asbestos bans. We do not find any significant effect on GDP following an asbestos ban. In a regional case study, we compare changes in GDP and employment with changes in asbestos production. Regional-level data revealed a temporary employment decline at the local level that was then reversed.}, } @article {pmid29545973, year = {2018}, author = {Naeini, YB and Arcega, R and Hirschowitz, S and Rao, N and Xu, H}, title = {Post-irradiation pericardial malignant mesothelioma with deletion of p16: a case report.}, journal = {Cancer biology & medicine}, volume = {15}, number = {1}, pages = {97-102}, pmid = {29545973}, issn = {2095-3941}, abstract = {Malignant mesotheliomas are rather uncommon neoplasms associated primarily with asbestos exposure; however, they may also arise as second primary malignancies after radiation therapy, with a latency period of 15-25 years. Numerous studies have reported an association between pleural malignant mesothelioma and chest radiation performed for other malignancies; on the other hand, post-irradiation mesotheliomas of the pericardium have been reported in only a few published cases to date, and no homozygous deletion of 9p21 has been described in such cases. We report the case of a 48-year-old man with a history of Hodgkin's lymphoma and no prior asbestos exposure who developed pericardial malignant epithelioid mesothelioma. We further discuss the cytologic, histologic, immunophenotypic, and fluorescence in situ hybridization findings in this case. To our knowledge, this is the first well-documented case of post-radiation pericardial malignant mesothelioma showing homozygous deletion of 9p21. Homozygous deletion of 9p21, the locus harboring the p16 gene, is present in post-irradiation pericardial malignant mesothelioma.}, } @article {pmid29534192, year = {2018}, author = {Gilham, C and Rake, C and Hodgson, J and Darnton, A and Burdett, G and Peto Wild, J and Newton, M and Nicholson, AG and Davidson, L and Shires, M and Treasure, T and Peto, J and , }, title = {Past and current asbestos exposure and future mesothelioma risks in Britain: The Inhaled Particles Study (TIPS).}, journal = {International journal of epidemiology}, volume = {47}, number = {6}, pages = {1745-1756}, pmid = {29534192}, issn = {1464-3685}, support = {//Cancer Research UK/United Kingdom ; }, mesh = {Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Asbestos, Amphibole/analysis ; Asbestos, Serpentine/analysis ; Carcinogens, Environmental/*adverse effects ; Environmental Exposure/*standards ; Female ; Humans ; Lung Neoplasms/etiology/*mortality ; Male ; Mesothelioma/etiology/*mortality ; Mesothelioma, Malignant ; Middle Aged ; Regression Analysis ; Risk Assessment ; Risk Factors ; United Kingdom/epidemiology ; }, abstract = {BACKGROUND: Occupational and environmental airborne asbestos concentrations are too low and variable for lifetime exposures to be estimated reliably, and building workers and occupants may suffer higher exposure when asbestos in older buildings is disturbed or removed. Mesothelioma risks from current asbestos exposures are therefore not known.

METHODS: We interviewed and measured asbestos levels in lung samples from 257 patients treated for pneumothorax and 262 with resected lung cancer, recruited in England and Wales. Average lung burdens in British birth cohorts from 1940 to 1992 were estimated for asbestos-exposed workers and the general population.

RESULTS: Regression analysis of British mesothelioma death rates and average lung burdens in birth cohorts born before 1965 suggests a lifetime mesothelioma risk of approximately 0.01% per fibre/mg of amphiboles in the lung. In those born since 1965, the average lung burden is ∼1 fibre/mg among those with no occupational exposure.

CONCLUSIONS: The average lifetime mesothelioma risk caused by recent environmental asbestos exposure in Britain will be about 1 in 10 000. The risk is an order of magnitude higher in a subgroup of exposed workers and probably in occupants in the most contaminated buildings. Further data are needed to discover whether asbestos still present in buildings, particularly schools, is a persistent or decreasing hazard to workers who disturb it and to the general population, and whether environmental exposure occurs predominantly in childhood or after beginning work. Similar studies are needed in other countries to estimate continuing environmental and occupational mesothelioma hazards worldwide, including the contribution from chrysotile.}, } @article {pmid29531907, year = {2018}, author = {van Zandwijk, N and McDiarmid, J and Brahmbhatt, H and Reid, G}, title = {Response to "An innovative mesothelioma treatment based on mir-16 mimic loaded EGFR targeted minicells (TargomiRs)".}, journal = {Translational lung cancer research}, volume = {7}, number = {Suppl 1}, pages = {S60-S61}, pmid = {29531907}, issn = {2218-6751}, } @article {pmid29524617, year = {2018}, author = {McCambridge, AJ and Napolitano, A and Mansfield, AS and Fennell, DA and Sekido, Y and Nowak, AK and Reungwetwattana, T and Mao, W and Pass, HI and Carbone, M and Yang, H and Peikert, T}, title = {Progress in the Management of Malignant Pleural Mesothelioma in 2017.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {13}, number = {5}, pages = {606-623}, pmid = {29524617}, issn = {1556-1380}, support = {R01 CA198138/CA/NCI NIH HHS/United States ; 15569/CRUK_/Cancer Research UK/United Kingdom ; 21400/CRUK_/Cancer Research UK/United Kingdom ; R01 CA160715/CA/NCI NIH HHS/United States ; U01 CA214195/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Immunotherapy/*methods/trends ; Lung Neoplasms/*therapy ; Mesothelioma/*therapy ; Mesothelioma, Malignant ; }, abstract = {Malignant pleural mesothelioma (MPM) is an uncommon, almost universally fatal, asbestos-induced malignancy. New and effective strategies for diagnosis, prognostication, and treatment are urgently needed. Herein we review the advances in MPM achieved in 2017. Whereas recent epidemiological data demonstrated that the incidence of MPM-related death continued to increase in United States between 2009 and 2015, new insight into the molecular pathogenesis and the immunological tumor microenvironment of MPM, for example, regarding the role of BRCA1 associated protein 1 and the expression programmed death receptor ligand 1, are highlighting new potential therapeutic strategies. Furthermore, there continues to be an ever-expanding number of clinical studies investigating systemic therapies for MPM. These trials are primarily focused on immunotherapy using immune checkpoint inhibitors alone or in combination with other immunotherapies and nonimmunotherapies. In addition, other promising targeted therapies, including pegylated adenosine deiminase (ADI-PEG20), which focuses on argininosuccinate synthase 1-deficient tumors, and tazemetostat, an enhancer of zeste 2 polycomb repressive complex 2 subunit inhibitor of BRCA1 associated protein 1 gene (BAP1)-deficient tumors, are currently being explored.}, } @article {pmid29523930, year = {2018}, author = {Casalone, E and Allione, A and Viberti, C and Pardini, B and Guarrera, S and Betti, M and Dianzani, I and Aldieri, E and Matullo, G}, title = {DNA methylation profiling of asbestos-treated MeT5A cell line reveals novel pathways implicated in asbestos response.}, journal = {Archives of toxicology}, volume = {92}, number = {5}, pages = {1785-1795}, doi = {10.1007/s00204-018-2179-y}, pmid = {29523930}, issn = {1432-0738}, mesh = {Antigens, Neoplasm/genetics ; Asbestos/chemistry/*toxicity ; Asbestos, Crocidolite/administration & dosage/toxicity ; Asbestos, Serpentine/administration & dosage/toxicity ; Carbonic Anhydrase IX/genetics ; Cell Line ; DNA Methylation/*drug effects ; Dose-Response Relationship, Drug ; Epithelial Cells/drug effects ; Humans ; Lung Neoplasms/chemically induced/genetics ; Mesothelioma/chemically induced/genetics ; Mesothelioma, Malignant ; Real-Time Polymerase Chain Reaction ; Transcriptome/*drug effects ; }, abstract = {Occupational and environmental asbestos exposure is the main determinant of malignant pleural mesothelioma (MPM), however, the mechanisms by which its fibres contribute to cell toxicity and transformation are not completely clear. Aberrant DNA methylation is a common event in cancer but epigenetic modifications involved specifically in MPM carcinogenesis need to be better clarified. To investigate asbestos-induced DNA methylation and gene expression changes, we treated Met5A mesothelial cells with different concentrations of crocidolite and chrysotile asbestos (0.5 ÷ 5.0 µg/cm[2], 72 h incubation). Overall, we observed 243 and 302 differentially methylated CpGs (≥ 10%) between the asbestos dose at 5 µg/cm[2] and untreated control, in chrysotile and crocidolite treatment, respectively. To examine the dose-response effect, Spearman's correlation test was performed and significant CpGs located in genes involved in migration/cell adhesion processes were identified in both treatments. Moreover, we found that both crocidolite and chrysotile exposure induced a significant up-regulation of CA9 and SRGN (log2 fold change > 1.5), previously reported as associated with a more aggressive MPM phenotype. However, we found no correlation between methylation and gene expression changes, except for a moderate significant inverse correlation at the promoter region of DKK1 (Spearman rho = - 1, P value = 0.02) after chrysotile exposure. These results describe for the first time the relationship between DNA methylation modifications and asbestos exposure. Our findings provide a basis to further explore and validate asbestos-induced DNA methylation changes, that could influence MPM carcinogenesis and possibly identifying new chemopreventive target.}, } @article {pmid29520212, year = {2018}, author = {Franko, A and Kotnik, N and Goricar, K and Kovac, V and Dodic-Fikfak, M and Dolzan, V}, title = {The Influence of Genetic Variability on the Risk of Developing Malignant Mesothelioma.}, journal = {Radiology and oncology}, volume = {52}, number = {1}, pages = {105-111}, pmid = {29520212}, issn = {1318-2099}, abstract = {BACKGROUND: Malignant mesothelioma is a rare cancer with poor outcome, associated with asbestos exposure. Reactive oxygen species may play an important role in the mechanism of carcinogenesis; therefore, genetic variability in antioxidative defence may modify an individual's susceptibility to this cancer. This study investigated the influence of functional polymorphisms of NQO1, CAT, SOD2 and hOGG1 genes, gene-gene interactions and gene-environment interactions on malignant mesothelioma risk.

PATIENTS AND METHODS: In total, 150 cases with malignant mesothelioma and 122 controls with no asbestos-related disease were genotyped for NQO1, CAT, SOD2 and hOGG1 polymorphisms.

RESULTS: The risk of malignant mesothelioma increased with smoking, odds ratio (OR) 9.30 [95% confidence interval (CI): 4.83-17.98] and slightly with age, OR 1.10 (95% CI: 1.08-1.14). Medium and high asbestos exposures represented 7-times higher risk of malignant mesothelioma compared to low exposure, OR 7.05 (95% CI 3.59-13.83). NQO1 rs1800566 was significantly associated with increased malignant mesothelioma risk, OR 1.73 (95% CI 1.02-2.96). Although there was no independent association between either CAT rs1001179 or hOGG1 rs1052133 polymorphism and malignant mesothelioma, interaction between both polymorphisms showed a protective effect, ORint 0.27 (95% CI 0.10-0.77).

CONCLUSIONS: Our findings suggest a role of both genetic variability in antioxidative defence and repair as well as the impact of gene-gene interactions in the development of malignant mesothelioma. The results of this study could add to our understanding of pathogenesis of malignant mesothelioma and contribute to prevention and earlier diagnosis of this aggressive cancer.}, } @article {pmid29508763, year = {2018}, author = {Scherpereel, A and Wallyn, F and Albelda, SM and Munck, C}, title = {Novel therapies for malignant pleural mesothelioma.}, journal = {The Lancet. Oncology}, volume = {19}, number = {3}, pages = {e161-e172}, doi = {10.1016/S1470-2045(18)30100-1}, pmid = {29508763}, issn = {1474-5488}, support = {P01 CA066726/CA/NCI NIH HHS/United States ; R01 CA172921/CA/NCI NIH HHS/United States ; }, mesh = {Angiogenesis Inhibitors/adverse effects/*therapeutic use ; Animals ; Antineoplastic Agents, Immunological/adverse effects/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use ; Humans ; Lung Neoplasms/*drug therapy/immunology/metabolism/pathology ; Mesothelioma/*drug therapy/immunology/metabolism/pathology ; Mesothelioma, Malignant ; Molecular Targeted Therapy/adverse effects/*methods ; Pleural Neoplasms/*drug therapy/immunology/metabolism/pathology ; Signal Transduction/drug effects ; Treatment Outcome ; }, abstract = {Malignant pleural mesothelioma is a rare cancer that is typically associated with exposure to asbestos. Patients with malignant pleural mesothelioma have poor outcomes with suboptimal therapeutic options and currently no treatment is curative. The standard frontline treatment, cisplatin plus pemetrexed chemotherapy, has only short and insufficient efficacy, and no validated treatment beyond first-line therapy is available. New therapeutic strategies are therefore needed. The addition of bevacizumab (an anti-VEGF antibody) combined with cisplatin plus pemetrexed has shown some promise. However, immunotherapy, especially immune checkpoint inhibitors, has generated a lot of excitement because of data suggesting the potential value of immune checkpoint inhibitors for patients who have failed chemotherapy. In this Review, we describe immune checkpoint inhibitors, other immunotherapies, targeted therapies, or combinations of novel drugs being investigated in malignant pleural mesothelioma, as well as the issues surrounding the selection of the best candidates for these treatments.}, } @article {pmid29507806, year = {2018}, author = {Foddis, R and Bonotti, A and Landi, S and Fallahi, P and Guglielmi, G and Cristaudo, A}, title = {Biomarkers in the prevention and follow-up of workers exposed to asbestos.}, journal = {Journal of thoracic disease}, volume = {10}, number = {Suppl 2}, pages = {S360-S368}, pmid = {29507806}, issn = {2072-1439}, abstract = {Although in most developed countries the use of asbestos is banned, there is still a consistent portion of the world where asbestos extraction, trading and manufacturing of asbestos-made products is largely diffuse. Worldwide, hundreds of millions of people are at risk of developing an asbestos caused disease because of occupational, environmental or domestic exposure. The WHO estimates that asbestos is responsible for more than 100,000 deaths yearly. This scenario has prompted the research on biomarkers potentially useful for early diagnosis, prognosis and preventive programs on exposed population as well. Here we reviewed the up-to-date literature on this field of research highlighting that along with mesothelin and osteopontin (OPN), some more recently investigated molecules, such as high mobility group box 1 (HMGB1) protein, fibulin-3 and some miRNAs showed very promising. Most of the carried-out studies showed an interesting diagnostic and prognostic performance of some biomarkers, but since they usually lack adequate either specificity or sensitivity, their use in screening or in preventive programs is still not recommended on a routine basis. However, this review suggests the need for more reliable experimental design involving larger population and preferring longitudinal screening of asbestos exposed individuals rather than a single baseline assessment investigation. In addition, given their better diagnostic accuracy, the use of panels including several biomarkers is highly recommended.}, } @article {pmid29507805, year = {2018}, author = {Cristaudo, A and Bonotti, A and Guglielmi, G and Fallahi, P and Foddis, R}, title = {Serum mesothelin and other biomarkers: what have we learned in the last decade?.}, journal = {Journal of thoracic disease}, volume = {10}, number = {Suppl 2}, pages = {S353-S359}, pmid = {29507805}, issn = {2072-1439}, abstract = {In the last decade there is been much interest in noninvasive, economic and well-accepted diagnostic tests for screening of subjects exposed to asbestos, and in patients with malignant pleuric mesothelioma (MPM) for diagnosis or monitoring response to treatment. Several biomarkers have been suggested as tools for screening and early diagnosis of MPM. Currently, in patients with MPM, have been reported high levels of soluble mesothelin-related peptides (SMRP), plasmatic osteopontin (pOPN), vimentin, fibulin-3 and many others as promising marker for diagnosis, even their use in prevention monitoring is still discussed. In this type of disease, a key role could be played by miRNAs, which expression has been investigated in a large series of MPM to examine new pathways useful in diagnosis, prognosis and therapy. An altered expression of some proteins has been reported, useful as biomarkers, in comparative proteomic analysis of malignant pleural mesothelioma. New promising markers are nowadays under study and alone or better in combination, they'll be very helpful in diagnosing, monitoring mesothelioma patients or for screening of risk groups.}, } @article {pmid29507804, year = {2018}, author = {Bruno, R and Alì, G and Fontanini, G}, title = {Molecular markers and new diagnostic methods to differentiate malignant from benign mesothelial pleural proliferations: a literature review.}, journal = {Journal of thoracic disease}, volume = {10}, number = {Suppl 2}, pages = {S342-S352}, pmid = {29507804}, issn = {2072-1439}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive tumor associated with asbestos exposure. Histopathological analysis of pleural tissues is the gold standard for diagnosis; however, it can be difficult to differentiate malignant from benign pleural lesions. The purpose of this review is to describe the most important biomarkers and new diagnostic tools suggested for this differential diagnosis. There are many studies concerning the separation between MPM and benign pleural proliferations from both pleural tissues or effusions; most of them are based on the evaluation of one or few biomarkers by immunohistochemistry (IHC) or enzyme-linked immunosorbent assays (ELISAs), whereas others focused on the identification of MPM signatures given by microRNA (miRNA) or gene expression profiles as well as on the combination of molecular data and classification algorithms. None of the reported biomarkers showed adequate diagnostic accuracy, except for p16 [evaluated by fluorescent in situ hybridization (FISH)] and BAP1 (evaluated by IHC), both biomarkers are recommended by the International Mesothelioma Interest Group guidelines for histological and cytological diagnosis. BAP1 and p16 showed a specificity of 100% in discerning malignant from benign lesions because they are exclusively unexpressed or deleted in MPM. However, their sensitivity, even when used together, is not completely sufficient, and absence of their alterations cannot confirm the benign nature of the lesion. Recently, the availability of new techniques and increasing knowledge regarding MPM genetics led to the definition of some molecular panels, including genes or miRNAs specifically deregulated in MPM, that are extremely valuable for differential diagnosis. Moreover, the development of classification algorithms is facilitating the application of molecular data for clinical practice. Data regarding new diagnostic tools and MPM signatures are absolutely promising; however, before their application in clinical practice, a prospective validation is necessary, as these approaches could surely improve the differential diagnosis between malignant and benign pleural lesions.}, } @article {pmid29507796, year = {2018}, author = {Alì, G and Bruno, R and Fontanini, G}, title = {The pathological and molecular diagnosis of malignant pleural mesothelioma: a literature review.}, journal = {Journal of thoracic disease}, volume = {10}, number = {Suppl 2}, pages = {S276-S284}, pmid = {29507796}, issn = {2072-1439}, abstract = {Malignant pleural mesothelioma (MPM), an asbestos-induced tumor, represents significant diagnostic challenges for pathologists. Its histological diagnosis is stepwise and should be based on morphological assessment, supported by clinical and radiological findings, and supplemented with immunohistochemistry (IHC) and, more recently, molecular tests. The main diagnostic dilemmas are the differential diagnoses with benign mesothelial proliferations and other pleural malignant tumors. The present review is an update regarding the morphological, immunohistochemical, and molecular features with respect to MPM diagnosis. Data sources include a survey of the biomedical literature from PubMed (http://www.ncbi.nlm.nih.gov/pubmed) and textbooks focusing on the pathological diagnosis of MPM and associated immunohistochemical and molecular markers. The histological findings of MPM could facilitate its diagnosis and provide important prognostic information. The immunohistochemical approach should rest on the application of a panel including positive (mesothelial-related) and negative markers with greater than 80% sensitivity and specificity, which need to be selected based on morphology and clinical information. Moreover, in challenging cases, fluorescent in situ hybridization (FISH) testing for the p16 deletion and IHC to evaluate the loss of BRCA1-associated protein 1 (BAP1) expression could be useful in distinguishing benign from malignant pleural proliferations.}, } @article {pmid29507795, year = {2018}, author = {Ceruti, P and Lonni, S and Baglivo, F and Marchetti, G}, title = {Endoscopic diagnosis and management of pleural effusion in malignant pleural mesothelioma.}, journal = {Journal of thoracic disease}, volume = {10}, number = {Suppl 2}, pages = {S269-S275}, pmid = {29507795}, issn = {2072-1439}, abstract = {Malignant pleural mesothelioma (MPM) is an asbestos-related aggressive tumor, that requires proper diagnosis and management. Symptoms are nonspecific and chest computed tomography (CT) and chest ultrasound (US) are important radiological tools in the initial workup to identify early pathological signs. Performing a medical thoracoscopy (MT) is essential for a definitive diagnosis of MPM. The procedure, integrated with a prior US, allows a global evaluation of the pleural cavity and the execution of multiple targeted biopsies, with low risk of complications. Some different endoscopic patterns are recognized. Thoracoscopic biopsies provide enough material to allow a thorough pathological and immunohistochemical characterization. The presence of extensive pleural adhesions and critical patient conditions are the only absolute contraindications. The clinical course of MPM is characterized by chronic symptoms such as chest pain and progressive dyspnea, the latter caused mainly by recurrent pleural effusion. Palliative interventions are required in order to relieve symptoms and improve the quality of life (QoL). These include thoracentesis, pleurodesis and the placement of an indwelling pleural catheter.}, } @article {pmid29507794, year = {2018}, author = {Falaschi, F and Romei, C and Fiorini, S and Lucchi, M}, title = {Imaging of malignant pleural mesothelioma: it is possible a screening or early diagnosis program?-a systematic review about the use of screening programs in a population of asbestos exposed workers.}, journal = {Journal of thoracic disease}, volume = {10}, number = {Suppl 2}, pages = {S262-S268}, pmid = {29507794}, issn = {2072-1439}, abstract = {Malignant pleural mesothelioma (MPM) in an uncommon neoplasia with high mortality rate, mostly related to professional asbestos exposure. Clinical manifestations are not specific so that diagnosis is performed at advanced stage and screening protocols are not feasible now. On the other hand, asbestos-exposed workers have a high incidence of developing lung cancer. Low-dose computed tomography (LDCT) is a volumetric acquisition technique with high spatial resolution and a low dose exposure; it is used in many trials to detect lung tumours at an early stage in screening protocols, reducing mortality rate in smoker subjects. In recent papers, the possibly role of lung cancer screening was evaluated and recommended also in subjects exposed to asbestos. This article summarizes previous and present clinical trials validated for lung cancer screening, to discuss the possibility of early diagnosis or screening programs in a population of asbestos exposed workers by LDCT.}, } @article {pmid29507793, year = {2018}, author = {Bianco, A and Valente, T and De Rimini, ML and Sica, G and Fiorelli, A}, title = {Clinical diagnosis of malignant pleural mesothelioma.}, journal = {Journal of thoracic disease}, volume = {10}, number = {Suppl 2}, pages = {S253-S261}, pmid = {29507793}, issn = {2072-1439}, abstract = {Malignant pleural mesothelioma (MPM) is a tumour which, despite progress in diagnostic procedures and biomolecular research, has poor prognosis. Symptoms reflect extension of disease and include shortness of breath and chest pain. Unexplained pleural effusion and pleural pain in patients exposed to asbestos should raise the suspicion of MPM. MPM diagnosis requires imaging procedures X-ray and computed tomography (CT) scans; magnetic resonance imaging (MRI) better defines the extension of the tumor while PET scanning provides additional information on metabolic activity, metastases, and response to treatment. Thoracoscopic biopsy remains the most appropriate procedure for definitive diagnosis of mesothelioma. Multimodality treatment including surgery, chemotherapy and radiotherapy has been associated with a better survival in selected patients. Clinical translational research including new approaches targeting immune-checkpoints is opening new horizons which may lead to personalised treatments.}, } @article {pmid29507792, year = {2018}, author = {Melaiu, O and Gemignani, F and Landi, S}, title = {The genetic susceptibility in the development of malignant pleural mesothelioma.}, journal = {Journal of thoracic disease}, volume = {10}, number = {Suppl 2}, pages = {S246-S252}, pmid = {29507792}, issn = {2072-1439}, abstract = {Malignant pleural mesothelioma (MPM) is a cancer of the pleural cavity whose main risk factor is exposure to asbestos. However, it has been shown that only a minority of exposed people develops MPM. In fact, the incidence among professionally exposed workers was shown to vary between 0.5% and 18.0%. Various hints suggested that other important cofactors could play a role, in particular the genetic susceptibility. Impressive is the case of Cappadocians families exposed to erionite and affected by an "epidemic" of MPM with about half of the inhabitants dying for the disease. However, no results for a "Cappadocia" gene of susceptibility to MPM have been obtained yet and more studies are needed. Among asbestos-exposed workers, several studies reported familial cases of MPM, suggesting that heredity could be important in the tumor development. However, large studies on familial clusters showed only weak increased risks that could be attributable also to indirect exposures in a contaminated household. Moreover, the risk of developing MPM is increased of a limited extent among people exposed to asbestos with a positive history of familial cancers. A particular is represented by carriers of germline mutations within BAP1 gene. In families and in animal models, mutations within BAP1 are strongly predisposing to develop MPM. However, also other types of cancer (such as uveal melanoma) are present, thus BAP1 mutations are considered as responsible for a hereditary form of a multi-cancer syndrome. In any case, among sporadic MPM, the prevalence of germline BAP1 mutations is negligible. Finally, genetic studies highlighted the presence of low-risk susceptibility alleles, such as those within XRCC3, NAT2 or GSTM1. Two different genome-wide association studies could not find positive associations reaching the genome-wide statistical significance threshold, however, both were concordant in showing a weak signal within the SDK1 gene region. Overall, it could be concluded that, as for other types of sporadic cancers, the susceptibility to develop MPM following asbestos exposure is modulated moderately by the individual genetic background. Further studies on larger series could help in a better characterization of more genes predisposing to MPM, being this tumor a rare disease.}, } @article {pmid29507791, year = {2018}, author = {Pira, E and Donato, F and Maida, L and Discalzi, G}, title = {Exposure to asbestos: past, present and future.}, journal = {Journal of thoracic disease}, volume = {10}, number = {Suppl 2}, pages = {S237-S245}, pmid = {29507791}, issn = {2072-1439}, abstract = {This paper summarises the past, present and future of asbestos exposure. The future scenarios as to the mesothelioma incidence in countries, where asbestos has been banned, are discussed.}, } @article {pmid29507789, year = {2018}, author = {Marinaccio, A and Binazzi, A and Bonafede, M and Di Marzio, D and Scarselli, A and , }, title = {Epidemiology of malignant mesothelioma in Italy: surveillance systems, territorial clusters and occupations involved.}, journal = {Journal of thoracic disease}, volume = {10}, number = {Suppl 2}, pages = {S221-S227}, pmid = {29507789}, issn = {2072-1439}, abstract = {BACKGROUND: As a legacy of the large asbestos consumption until the definitive ban in 1992, Italy is currently suffering a severe epidemic of asbestos related diseases. The aim of this paper is to describe the surveillance system for mesothelioma incidence and to provide evidences regarding the occurrence of the disease in Italy and the circumstances of asbestos exposure.

METHODS: Italian National Register of Malignant Mesotheliomas (ReNaM) is a permanent surveillance system of mesothelioma incidence, with Regional Operating Centres (CORs) active in each Italian region, identifying incident malignant mesothelioma (MM) cases from health care structures. Occupational history, lifestyle habits and residential history are obtained using a standardised questionnaire, administered by a trained interviewer, to the subject or to the next of kin. Descriptive epidemiological figures, occupations involved in exposures and territorial maps of MM cases have been produced.

RESULTS: At December 2016, ReNaM has collected 27,356 MM cases for the incidence period between 1993 and 2015. The modalities of exposure to asbestos have been investigated for 21,387 (78%) and an occupational exposure has been defined for around 70% of interviewed cases (14,818). Non-occupational exposure is still relevant with 4.9% and 4.4% of cases for which respectively a familial exposure (due to the cohabitation with an occupational exposed subject) and an environmental exposure (due to the residence near a contaminated site) has been detected.

DISCUSSION: The epidemiological surveillance of MM incident cases, by the means of a national register for estimating the occurrence of the disease and identifying the circumstances of asbestos exposure, is a relevant tool for preventing asbestos exposure, for supporting the effectiveness of insurance system and for estimating reliable epidemiological figures.}, } @article {pmid29507420, year = {2018}, author = {Rehrauer, H and Wu, L and Blum, W and Pecze, L and Henzi, T and Serre-Beinier, V and Aquino, C and Vrugt, B and de Perrot, M and Schwaller, B and Felley-Bosco, E}, title = {How asbestos drives the tissue towards tumors: YAP activation, macrophage and mesothelial precursor recruitment, RNA editing, and somatic mutations.}, journal = {Oncogene}, volume = {37}, number = {20}, pages = {2645-2659}, pmid = {29507420}, issn = {1476-5594}, mesh = {Adaptor Proteins, Signal Transducing ; Animals ; Asbestos, Crocidolite/*adverse effects ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; *Gene Regulatory Networks ; Humans ; Intracellular Signaling Peptides and Proteins/metabolism ; Lung Neoplasms/chemically induced/*genetics/metabolism ; Macrophage Activation ; Mesothelioma/chemically induced/*genetics/metabolism ; Mesothelioma, Malignant ; Mice ; Mutation ; Phosphoproteins ; Polymorphism, Single Nucleotide ; *RNA Editing ; Trans-Activators ; Transcription Factors ; *Transcriptional Activation ; Transcriptional Coactivator with PDZ-Binding Motif Proteins ; YAP-Signaling Proteins ; }, abstract = {Chronic exposure to intraperitoneal asbestos triggered a marked response in the mesothelium well before tumor development. Macrophages, mesothelial precursor cells, cytokines, and growth factors accumulated in the peritoneal lavage. Transcriptome profiling revealed YAP/TAZ activation in inflamed mesothelium with further activation in tumors, paralleled by increased levels of cells with nuclear YAP/TAZ. Arg1 was one of the highest upregulated genes in inflamed tissue and tumor. Inflamed tissue showed increased levels of single-nucleotide variations, with an RNA-editing signature, which were even higher in the tumor samples. Subcutaneous injection of asbestos-treated, but tumor-free mice with syngeneic mesothelioma tumor cells resulted in a significantly higher incidence of tumor growth when compared to naïve mice supporting the role of the environment in tumor progression.}, } @article {pmid29506546, year = {2018}, author = {Yin, W and Zheng, G and Yang, K and Song, H and Liang, Y}, title = {Analysis of prognostic factors of patients with malignant peritoneal mesothelioma.}, journal = {World journal of surgical oncology}, volume = {16}, number = {1}, pages = {44}, pmid = {29506546}, issn = {1477-7819}, support = {1213018ZD//Cangzhou Science and Technology Research and Development Plan/ ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Biomarkers, Tumor/*analysis ; Cisplatin/administration & dosage ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/drug therapy/*pathology ; Lymphocytes/*pathology ; Male ; Mesothelioma/drug therapy/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Neutrophils/*pathology ; Pemetrexed/administration & dosage ; Peritoneal Neoplasms/drug therapy/*pathology ; Prognosis ; Retrospective Studies ; Survival Rate ; }, abstract = {BACKGROUND: The study aims to find out independent prognostic factors for patients with malignant peritoneal mesothelioma (MPeM).

METHODS: Patients with pathologically proven MPeM were retrospectively reviewed. Potential prognostic factors were analyzed, including age, gender, asbestos exposure, body mass index (BMI), treatment, and laboratory results, such as blood routine examination and liver functions. The influences of various risk factors on the prognoses were analyzed by univariate analysis. A Cox regression model analysis established independent factors for the survival prognosis of the patients.

RESULTS: Seventy MPeM patients, including 33 patients who received intraperitoneal chemotherapy with cisplatin, 14 patients who received systemic chemotherapy with cisplatin + pemetrexed, and 21 untreated patients were included in this study. The 1-year survival was 32.9%, the 2-year survival was 10%, and the 3-year survival was 2.9%. The median age of MPeM was 62 years, and the female-to-male ratio was 1:0.56. The univariate and multivariate analyses showed that treatment, albumin (ALB), and blood neutrophil-to-lymphocyte ratio (NLR) were independent factors that affected the overall survival (OS) of MPeM patients.

CONCLUSION: High blood NLR and hypoalbuminemia are adverse prognostic factors for MPeM patients. Systemic chemotherapy and intraperitoneal chemotherapy can prolong the survival period.}, } @article {pmid29498660, year = {2018}, author = {Pietrofesa, RA and Chatterjee, S and Park, K and Arguiri, E and Albelda, SM and Christofidou-Solomidou, M}, title = {Synthetic Lignan Secoisolariciresinol Diglucoside (LGM2605) Reduces Asbestos-Induced Cytotoxicity in an Nrf2-Dependent and -Independent Manner.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {7}, number = {3}, pages = {}, pmid = {29498660}, issn = {2076-3921}, support = {P30 ES013508/ES/NIEHS NIH HHS/United States ; P42 ES023720/ES/NIEHS NIH HHS/United States ; R21 AT008291/AT/NCCIH NIH HHS/United States ; R03 CA180548/CA/NCI NIH HHS/United States ; R01 CA133470/CA/NCI NIH HHS/United States ; }, abstract = {Asbestos exposure triggers inflammatory processes associated with oxidative stress and tissue damage linked to malignancy. LGM2605 is the synthetic lignan secoisolariciresinol diglucoside (SDG) with free radical scavenging, antioxidant, and anti-inflammatory properties in diverse inflammatory cell and mouse models, including exposure to asbestos fibers. Nuclear factor-E2 related factor 2 (Nrf2) activation and boosting of endogenous tissue defenses were associated with the protective action of LGM2605 from asbestos-induced cellular damage. To elucidate the role of Nrf2 induction by LGM2605 in protection from asbestos-induced cellular damage, we evaluated LGM2605 in asbestos-exposed macrophages from wild-type (WT) and Nrf2 disrupted (Nrf2[-]/[-]) mice. Cells were pretreated with LGM2605 (50 µM and 100 µM) and exposed to asbestos fibers (20 µg/cm[2]) and evaluated 8 h and 24 h later for inflammasome activation, secreted cytokine levels (interleukin-1β (IL-1β), interleukin-18 (IL-18), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNFα)), cytotoxicity and cell death, nitrosative stress, and Nrf2-regulated enzyme levels. Asbestos exposure induced robust oxidative and nitrosative stress, cell death and cytotoxicity, which were equally mitigated by LGM2605. Inflammasome activation was significantly attenuated in Nrf2[-/-] macrophages compared to WT, and the protective action of LGM2605 was seen only in WT cells. In conclusion, in a cell model of asbestos-induced toxicity, LGM2605 acts via protective mechanisms that may not involve Nrf2 activation.}, } @article {pmid29495596, year = {2018}, author = {Angelico, G and Caltabiano, R and Loreto, C and Ieni, A and Tuccari, G and Ledda, C and Rapisarda, V}, title = {Immunohistochemical Expression of Aquaporin-1 in Fluoro-Edenite-Induced Malignant Mesothelioma: A Preliminary Report.}, journal = {International journal of molecular sciences}, volume = {19}, number = {3}, pages = {}, pmid = {29495596}, issn = {1422-0067}, mesh = {Aged ; Aged, 80 and over ; Aquaporin 1/genetics/*metabolism ; Asbestos, Amphibole/*adverse effects ; Biomarkers, Tumor ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lung Neoplasms/*etiology/*metabolism/mortality/pathology ; Male ; Mesothelioma/*etiology/*metabolism/mortality/pathology ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/*etiology/*metabolism/pathology ; Prognosis ; Proportional Hazards Models ; }, abstract = {BACKGROUND: The immunohistochemical expression of aquaporin-1 (AQP1) in asbestos-related malignant pleural mesothelioma (MPM) is emerging as a useful prognostic indicator of improved survival. A significantly increased incidence of MPM in a small town in southern Italy was ascribed to exposure to fluoro-edenite (FE), a naturally occurring asbestos fiber. We investigated the immunohistochemical expression of AQP1 in patients affected by FE-related MPM; taking into consideration its suggested independent prognostic role, its possible correlation with clinicopathological parameters and patient outcome was also evaluated.

METHODS: Ten patients were selected for this study, as neoplastic tissue blocks, clinical and follow-up data were available. The immunohistochemical overexpression of AQP1 was defined as ≥50% of tumor cells showing membranous staining.

RESULTS: Six cases showed AQP1 expression in ≥50% of tumor cells; in this group, a significant association of AQP1 overexpression with an increased median overall survival (OS) of 26.3 months was observed. By contrast, four patients exhibited an AQP1 score of <50% of stained cells, with a shorter median OS of 8.9 months.

CONCLUSIONS: The present study represents further confirmation of the hypothesized prognostic role of AQP1, which seems a reliable prognostic indicator.}, } @article {pmid29480760, year = {2018}, author = {Attanoos, RL and Churg, A and Galateau-Salle, F and Gibbs, AR and Roggli, VL}, title = {Malignant Mesothelioma and Its Non-Asbestos Causes.}, journal = {Archives of pathology & laboratory medicine}, volume = {142}, number = {6}, pages = {753-760}, doi = {10.5858/arpa.2017-0365-RA}, pmid = {29480760}, issn = {1543-2165}, mesh = {Asbestos, Serpentine/adverse effects ; Europe ; Female ; Germ-Line Mutation ; Humans ; Lung Neoplasms/chemically induced/*etiology/genetics/pathology ; Male ; Mesothelioma/chemically induced/*etiology/genetics/pathology ; Mesothelioma, Malignant ; Nanotubes, Carbon/adverse effects ; North America ; Peritoneal Neoplasms/chemically induced/*etiology/genetics/pathology ; Pleural Neoplasms/chemically induced/*etiology/genetics/pathology ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; Zeolites/adverse effects ; }, abstract = {CONTEXT: - Although many mesotheliomas are related to asbestos exposure, not all are, and there is increasing information on other causes of mesothelioma.

OBJECTIVE: - To provide a review of non-asbestos causes for malignant mesothelioma.

DATA SOURCES: - Review of relevant published literature via PubMed and other search engines.

CONCLUSIONS: - Currently, most pleural mesotheliomas (70% to 90%) in men in Europe and North America are attributable to asbestos exposure; for peritoneal mesothelioma the proportion is lower. In North America few mesotheliomas in women at any site are attributable to asbestos exposure, but in Europe the proportion is higher and varies considerably by locale. In certain geographic locations other types of mineral fibers (erionite, fluoro-edenite, and probably balangeroite) can induce mesothelioma. Therapeutic radiation for other malignancies is a well-established cause of mesothelioma, with relative risks as high as 30. Carbon nanotubes can also induce mesotheliomas in animals but there are no human epidemiologic data that shed light on this issue. Chronic pleural inflammation may be a cause of mesothelioma but the data are scanty. Although SV40 can induce mesotheliomas in animals, in humans the epidemiologic data are against a causative role. A small number of mesotheliomas (probably in the order of 1%) are caused by germline mutations/deletions of BRCA1-associated protein-1 (BAP1) in kindreds that also develop a variety of other cancers. All of these alternative etiologies account for a small proportion of tumors, and most mesotheliomas not clearly attributable to asbestos exposure are spontaneous (idiopathic).}, } @article {pmid29473898, year = {2018}, author = {Soeberg, M and Vallance, DA and Keena, V and Takahashi, K and Leigh, J}, title = {Australia's Ongoing Legacy of Asbestos: Significant Challenges Remain Even after the Complete Banning of Asbestos Almost Fifteen Years Ago.}, journal = {International journal of environmental research and public health}, volume = {15}, number = {2}, pages = {}, pmid = {29473898}, issn = {1660-4601}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Asbestosis/*epidemiology/*etiology/prevention & control ; Australia/epidemiology ; Female ; *Health Policy ; Humans ; Lung Neoplasms/*chemically induced/*epidemiology ; Male ; Mesothelioma/*chemically induced/*epidemiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/adverse effects/*legislation & jurisprudence ; }, abstract = {The most effective way of reducing the global burden of asbestos-related diseases is through the implementation of asbestos bans and minimising occupational and non-occupational exposure to respirable asbestos fibres. Australia's asbestos consumption peaked in the 1970s with Australia widely thought to have had among the highest per-capita asbestos consumption level of any country. Australia's discontinuation of all forms of asbestos and asbestos-containing products and materials did not occur at a single point of time. Crocidolite consumption ceased in the late 1960s, followed by amosite consumption stopping in the mid 1980s. Despite significant government reports being published in 1990 and 1999, it was not until the end of 2003 that a complete ban on all forms of asbestos (crocidolite, amosite, and chrysotile) was introduced in Australia. The sustained efforts of trade unions and non-governmental organisations were essential in forcing the Australian government to finally implement the 2003 asbestos ban. Trade unions and non-government organisations continue to play a key role today in monitoring the government's response to Australian asbestos-related disease epidemic. There are significant challenges that remain in Australia, despite a complete asbestos ban being implemented almost fifteen years ago. The Australian epidemic of asbestos-related disease has only now reached its peak. A total of 16,679 people were newly diagnosed with malignant mesothelioma between 1982 and 2016, with 84% of cases occurring in men. There has been a stabilisation of the age-standardised malignant mesothelioma incidence rate in the last 10 years. In 2016, the incidence rate per 100,000 was 2.5 using the Australian standard population and 1.3 using the Segi world standard population. Despite Australia's complete asbestos ban being in place since 2003, public health efforts must continue to focus on preventing the devastating effects of avoidable asbestos-related diseases, including occupational and non-occupational groups who are potentially at risk from exposure to respirable asbestos fibres.}, } @article {pmid29458304, year = {2017}, author = {Barlow, CA and Grespin, M and Best, EA}, title = {Asbestos fiber length and its relation to disease risk.}, journal = {Inhalation toxicology}, volume = {29}, number = {12-14}, pages = {541-554}, doi = {10.1080/08958378.2018.1435756}, pmid = {29458304}, issn = {1091-7691}, mesh = {Animals ; Asbestos/metabolism/*toxicity ; Carcinogens/metabolism/*toxicity ; Cells, Cultured ; Environmental Exposure/adverse effects ; Humans ; Lung/*drug effects/metabolism/pathology ; Mineral Fibers/*toxicity ; Occupational Exposure/adverse effects ; Pulmonary Fibrosis/chemically induced/metabolism/pathology ; Risk Factors ; }, abstract = {Differences in chemical and crystalline composition, fiber dimension, aerodynamic characteristics and biodurability are among the critical factors that define the toxicological and pathological consequences of asbestos exposure. Specifically, fiber dimension can impact whether the fiber is respired, whether and how deeply it is deposited in the lung, and how efficiently and rapidly it may be cleared. This paper provides a current, comprehensive evaluation of the weight of evidence regarding the relationship between asbestos fiber length and disease potency (for malignant and nonmalignant endpoints). In vitro studies, animal exposure studies and epidemiology data were reviewed. We found that the data reported over the last several decades consistently support the conclusions that exposure to fibers longer than 10 µm and perhaps 20 µm are required to significantly increase the risk of developing asbestos-related disease in humans and that there is very little, if any, risk associated with exposure to fibers shorter than 5 µm. Fiber length as a predictor of potency has been evaluated by several federal agencies in the U.S. and could significantly influence future regulatory decisions for elongated mineral particles (EMPs) and high-aspect ratio nanoparticles (HARNs).}, } @article {pmid29438360, year = {2018}, author = {Linton, A and Cheng, YY and Griggs, K and Schedlich, L and Kirschner, MB and Gattani, S and Srikaran, S and Chuan-Hao Kao, S and McCaughan, BC and Klebe, S and van Zandwijk, N and Reid, G}, title = {An RNAi-based screen reveals PLK1, CDK1 and NDC80 as potential therapeutic targets in malignant pleural mesothelioma.}, journal = {British journal of cancer}, volume = {118}, number = {6}, pages = {e13}, doi = {10.1038/bjc.2018.3}, pmid = {29438360}, issn = {1532-1827}, abstract = {This corrects the article DOI: 10.1038/bjc.2017.85.}, } @article {pmid29435293, year = {2018}, author = {Yano, M and Ikeda, Y and Kato, T and Sakaki, M and Sato, S and Yabuno, A and Kozawa, E and Yasuda, M}, title = {A case of peritoneal malignant mesothelioma following radiation therapy for cervical cancer.}, journal = {Molecular and clinical oncology}, volume = {8}, number = {2}, pages = {302-305}, pmid = {29435293}, issn = {2049-9450}, abstract = {The present study presents a case of peritoneal malignant mesothelioma (PMM) following radiation therapy for cervical cancer. A 34-year-old Japanese woman, without asbestos exposure, was referred to the Department of Gynecologic Oncology, Saitama Medical University International Medical Center due to a cervical mass, and was diagnosed with cervical squamous cell carcinoma (SCC). The serum levels of tumor markers, including SCC antigen and cancer antigen 125 (CA125) were 229.0 ng/ml and 54.4 U/ml, respectively. The patient underwent concurrent chemoradiotherapy (CCRT), and a complete response was achieved. After 54 months, ascites was found at the rectouterine pouch, but peritoneal cytology suggested reactive mesothelial cell. After 62 months of CCRT, magnetic resonance imaging revealed masses in both the salpinges. The serum levels of SCC and CA125 were 0.9 ng/ml and 506.1 U/ml, respectively. Following this, left salpingectomy and peritoneal biopsy were performed laparoscopically. Histologic examination revealed atypical mesothelial cells with no continuity of background tubal epithelium. Immunohistochemistry showed positive staining for calretinin, thrombomodulin, mesothelin and glucose transporter 1. Based on these findings, the patient was diagnosed with PMM epithelioid type and underwent systemic chemotherapy; stable disease status has been obtained for 3 months. This case demonstrates the possibility of PMM occurrence within 10 years after radiotherapy, and indicates the importance of histological and immunohistochemical examination, particularly in cases of an atypical tumorigenesis pattern from the primary cancer.}, } @article {pmid29434985, year = {2018}, author = {Yoneda, K and Chikaishi, Y and Kuwata, T and Ohnaga, T and Tanaka, F}, title = {Capture of mesothelioma cells with 'universal' CTC-chip.}, journal = {Oncology letters}, volume = {15}, number = {2}, pages = {2635-2640}, pmid = {29434985}, issn = {1792-1074}, abstract = {Malignant mesothelioma (MM) is a highly aggressive malignant tumor, predominantly associated with job-related exposure to asbestos. Development of effective and non-invasive modalities for diagnosis is an important issue in occupational medicine. Circulating tumor cells (CTCs), which are tumor cells that are shed from primary tumors and circulate in the peripheral blood, may be detected at an earlier stage than malignant tumors, and detection of CTCs may provide a novel insight into the diagnosis of MM. In a previous study evaluating clinical utility of CTCs, detected with a widely used system 'CellSearch', the authors indicated a significant however insufficient capability in the diagnosis of MM, suggesting need for a more sensitive system. Accordingly, the authors developed a novel microfluidic system to capture CTCs (CTC-chip), and demonstrated that the CTC-chip effectively captured MM cells (ACC-MESO-4) spiked in the blood by conjugating an anti-podoplanin antibody. The results of the present study demonstrated that the CTC-chip coated with the anti-podoplanin antibody captured another MM cell (ACC-MESO-1). However, the capture efficiencies were lower than those for ACC-MESO-4. In addition, an anti-mesothelin antibody was used to capture CTCs, however the CTC-chip coated with the anti-mesothelin antibody failed to effectively capture MM cells, possibly due to low mesothelin expression. Overall, the CTC-chip may capture specific types of CTCs by conjugating any antibody against an antigen expressed on CTCs, and may be a useful system for the diagnosis of malignant tumors, including MM.}, } @article {pmid29430704, year = {2018}, author = {Tanaka, H and Akiyama, Y and Kitamura, A and Matsumoto, N and Tomita, M and Kataoka, H}, title = {Malignant mesothelioma with squamous differentiation.}, journal = {Histopathology}, volume = {72}, number = {7}, pages = {1216-1220}, doi = {10.1111/his.13482}, pmid = {29430704}, issn = {1365-2559}, mesh = {Carcinoma, Squamous Cell/*diagnosis/pathology ; Diagnosis, Differential ; Humans ; Lung Neoplasms/*diagnosis/pathology ; Male ; Mesothelioma/*diagnosis/pathology ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/*diagnosis/pathology ; }, abstract = {AIMS: We report the autopsy findings of a 58-year-old man with malignant mesothelioma in the left pleural cavity.

METHODS AND RESULTS: The patient had a history of asbestos exposure, and the chest computed tomography scan on initial admission demonstrated an extrapleural sign, suggesting a nodular lesion in the chest wall. However, no nodular lesions were detectable in either of his lungs. In spite of chemotherapy, he died 4 months after the initial admission. An autopsy revealed markedly thickened pleura in a large section of the left pleural cavity without visible intrapulmonary primary tumour lesions. Histological examination of a biopsy specimen obtained prior to chemotherapy and that of an autopsy specimen showed that the pleural tumour was composed of a mixture of mesothelioma and tumour cells with squamous differentiation mimicking squamous cell carcinoma.

CONCLUSIONS: To the best of our knowledge, this is the first case report of mesothelioma with extensive squamous differentiation in the English-language literature. The extensive squamous differentiation reminiscent of squamous cell carcinoma can be a pitfall in the pathological diagnosis of pleural cytology and that of biopsy specimens from patients with mesothelioma. Here, we report autopsy findings of a case of malignant mesothelioma with portions of extensive squamous differentiation, mimicking a squamous cell carcinoma.}, } @article {pmid29424961, year = {2018}, author = {Abdel-Rahman, O}, title = {Global trends in mortality from malignant mesothelioma: Analysis of WHO mortality database (1994-2013).}, journal = {The clinical respiratory journal}, volume = {12}, number = {6}, pages = {2090-2100}, doi = {10.1111/crj.12778}, pmid = {29424961}, issn = {1752-699X}, mesh = {Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Cross-Sectional Studies ; Databases, Factual ; Female ; Global Health ; Humans ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; Mesothelioma, Malignant ; Middle Aged ; *Registries ; Retrospective Studies ; Sex Distribution ; Survival Rate/trends ; }, abstract = {BACKGROUND AND OBJECTIVE: Little is known about the extent to which asbestos use ban has affected global trends in malignant mesothelioma. This study investigated recent global mortality trends of malignant mesothelioma.

METHODS: Data were collected from International Agency for Research on Cancer/World Health Organization mortality database to examine age-standardized, gender-specific mortality rates for malignant mesothelioma (ICD10-C45). Cross-sectional mortality rates (2009-2013) as well as trends over time (1994-2013) were also reported. Gender-specific annual percent change (APC) was calculated to examine trends over time for each country.

RESULTS: Among the 30 countries with highest mesothelioma mortality in men, there is almost 10-fold variation in mortality rates during 2009-2013 ranging from 6.25 per 100 000 for United Kingdom to 0.64 per 100 000 in Portugal; whereas, among the 30 countries with highest mesothelioma mortality in women, there is a 4-fold variation in mortality rates during 2009-2013 ranging from 1.08 per 100 000 for United Kingdom to 0.26 per 100 000 in Ireland. Mortality rates were higher in men compared to women in 32 out of 35 evaluable countries. Among males and over the last 10 years of covered years, mesothelioma mortality was significantly declining in 9 countries (United Kingdom, Sweden, France, Germany, Netherlands, Canada, United States, Australia, and New Zealand); whereas, it was significantly rising in 5 countries (Poland, Spain, China-Hong Kong, Japan, and Republic of Korea). In the remaining countries, APC was stable. Among females and over the last 10 years of covered years, mesothelioma mortality was significantly declining in 1 country only (Italy); whereas, it was significantly rising in 3 countries (Poland, Argentina, and Republic of Korea). In the remaining countries, APC was stable.

CONCLUSIONS: There is a worldwide variability in the burden and trends of mesothelioma mortality; and despite the ban on asbestos in many countries, mesothelioma still represents an important cause of mortality.}, } @article {pmid29421994, year = {2017}, author = {Fathi Fathabadi, MK and Abdolahnejad, A and Teiri, H and Hajizadeh, Y}, title = {Spatio-seasonal variation of airborne asbestos concentration in urban areas of Shiraz, Iran.}, journal = {International journal of occupational and environmental health}, volume = {23}, number = {2}, pages = {143-150}, pmid = {29421994}, issn = {2049-3967}, mesh = {Air Pollutants, Occupational/*analysis ; Asbestos/*analysis ; Cities ; *Construction Industry ; *Environmental Monitoring ; Geographic Information Systems ; Iran ; Microscopy, Electron, Scanning ; Microscopy, Phase-Contrast ; Seasons ; Spatial Analysis ; }, abstract = {Background Asbestos fiber is mainly released from friction product in brakes and clutch linings and from reinforcing agent in the asbestos-cement industry. It leads to serious health problem such as mesothelioma and lung cancer. The objectives of this study were to monitor the levels of asbestos fibers in ambient air of Shiraz, Iran during 2014, and to draw its GIS distribution map for the city. Methods Samples were collected by mixed cellulose ester filters mounted on an open-faced filter holder using a SKC sampling pump. Fiber counting was conducted using both phase contrast microscopy (PCM) method to determine total fibers, and scanning electron microscopy (SEM) method to identify non-asbestos from asbestos fibers. Results The average concentrations of asbestos fibers in ambient air of the city were 1.11 ± 0.25 PCM f/l and 12.21 ± 2.52 SEM f/l. The highest concentration of asbestos fibers was measured in Valiasr square amounting 1.96 ± 0.34 PCM f/l and 16.87 ± 2.14 SEM f/l. Conclusions The average of asbestos fibers in all sampling points was higher than the WHO guideline (0.05 PCM f/l, 2.2 SEM f/l). This may be attributed to the frequently occurrence of heavy traffic, the existence of relevant industries in and around the city, and the topographic characteristics of the city. Thus, product substitution, traffic smoothing and industrial sites relocating are suggested to eliminate the asbestos fibers emission.}, } @article {pmid29419731, year = {2018}, author = {Kumagai-Takei, N and Yamamoto, S and Lee, S and Maeda, M and Masuzzaki, H and Sada, N and Yu, M and Yoshitome, K and Nishimura, Y and Otsuki, T}, title = {Inflammatory Alteration of Human T Cells Exposed Continuously to Asbestos.}, journal = {International journal of molecular sciences}, volume = {19}, number = {2}, pages = {}, pmid = {29419731}, issn = {1422-0067}, mesh = {Animals ; Apoptosis ; Asbestos/administration & dosage/*adverse effects/metabolism ; Biomarkers ; Carcinogens ; Cytokines ; Environmental Exposure ; Humans ; Inflammation/*etiology/metabolism/pathology ; Inflammation Mediators ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Mesothelioma, Malignant ; T-Lymphocytes/*drug effects/immunology/metabolism ; }, abstract = {Asbestos is a known carcinogen and exposure can lead to lung cancer and malignant mesothelioma. To examine the effects of asbestos fibers on human immune cells, the human T cell leukemia/lymphoma virus (HTLV)-1 immortalized human T cell line MT-2 was employed. Following continuous exposure to asbestos fibers for more than eight months, MT-2 sublines showed acquisition of resistance to asbestos-induced apoptosis with decreased death signals and increased surviving signals. These sublines showed various characteristics that suggested a reduction in anti-tumor immunity. On the other hand, inflammatory changes such as expression of MMP7, CXCR5, CXCL13 and CD44 was found to be markedly higher in sublines continuously exposed to asbestos compared with original MT-2 cells. All of these molecules contribute to lung inflammation, T and B cell interactions and connections between mesothelial cells and T cells. Thus, further investigation focusing on these molecules may shed light on the role of chronic inflammation caused by asbestos exposure and the occurrence of malignant mesothelioma. Finally, regarding peripheral T cells from healthy donors (HD) and asbestos-exposed patients with pleural plaque (PP) or malignant pleural mesothelioma (MPM), following stimulation of CD4+ T cells, T cells from MPM patients showed reduced potential of interferon (IFN)-γ expression. Moreover, levels of interleukin (IL)-6, one of the most important cytokines in chronic inflammation, in cultured supernatants were higher in PP and MPM patients compared with HD. Overall, asbestos-induced chronic inflammation in the lung as well as the pleural cavity may facilitate the onset of asbestos-induced cancers due to alterations in the interactions among fibers, immune cells such as T and B cells and macrophages, and mesothelial and lung epithelial cells. Further investigations regarding chronic inflammation caused by asbestos fibers may assist in identifying molecular targets for preventive and therapeutic strategies related to the effects of asbestos exposure.}, } @article {pmid29416614, year = {2018}, author = {Thompson, JK and Shukla, A and Leggett, AL and Munson, PB and Miller, JM and MacPherson, MB and Beuschel, SL and Pass, HI and Shukla, A}, title = {Extracellular signal regulated kinase 5 and inflammasome in progression of mesothelioma.}, journal = {Oncotarget}, volume = {9}, number = {1}, pages = {293-305}, pmid = {29416614}, issn = {1949-2553}, support = {R01 ES021110/ES/NIEHS NIH HHS/United States ; S10 RR019246/RR/NCRR NIH HHS/United States ; }, abstract = {Malignant mesothelioma is an aggressive cancer in desperate need of treatment. We have previously shown that extracellular signaling regulated kinase 5 (ERK5) plays an important role in mesothelioma pathogenesis using ERK5 silenced human mesothelioma cells exhibiting significantly reduced tumor growth in immunocompromised mice. Here, we used a specific ERK 5 inhibitor, XMD8-92 in various in vitro and in vivo models to demonstrate that inhibition of ERK5 can slow down mesothelioma tumorigenesis. First, we show a dose dependent toxicity of XMD8-92 to 2 human mesothelioma cell lines growing as a monolayer. We also demonstrate the inhibition of ERK5 phosphorylation in various human mesothelioma cell lines by XMD8-92. We further confirmed the toxicity of XMD8-92 towards mesothelioma cell lines grown as spheroids in a 3-D model as well as in intraperitoneal (immune-competent) and intrapleural (immune-deficient) mouse models with and without chemotherapeutic drugs. To ascertain the mechanism, we explored the role of the nod-like receptor family member containing a pyrin domain 3 (NLRP3) inflammasome in the process. We found XMD8-92 attenuated naïve and chemotherapeutic-induced inflammasome priming and activation in mesothelioma cells. It can thus be concluded that ERK5 inhibition attenuates mesothelioma tumor growth and this phenomenon in part is regulated by the inflammasome.}, } @article {pmid29415822, year = {2018}, author = {Scherpereel, A and Willemin, MC and Wasielewski, E and Dhalluin, X}, title = {[Anti-tumor immunotherapy in malignant pleural mesothelioma].}, journal = {Revue des maladies respiratoires}, volume = {35}, number = {4}, pages = {465-476}, doi = {10.1016/j.rmr.2017.07.025}, pmid = {29415822}, issn = {1776-2588}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Bevacizumab/administration & dosage/adverse effects ; Cisplatin/administration & dosage/adverse effects ; Combined Modality Therapy ; Humans ; Immunotherapy/*methods ; Lung Neoplasms/*drug therapy ; Mesothelioma/*drug therapy ; Mesothelioma, Malignant ; Pemetrexed/administration & dosage/adverse effects ; Pleural Neoplasms/*drug therapy ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is a quite rare cancer, but with increasing incidence, that is usually induced by previous asbestos exposure. Its prognosis is poor and there is no validated curative therapy to date. Surgery of MPM, done only by few expert teams within a multimodal treatment is of limited and still disputed value. The standard treatment of MPM, relying on first-line chemotherapy by combined cisplatin-pemetrexed is often poorly effective, even if combination with bevacizumab anti-VEGF antibodies has slightly improved the results. Moreover, no second line treatment is recommended in case of failure of this chemotherapy. Therefore, the search of new therapies or strategies is crucial and the recruitment of patients in clinical trials is highly encouraged.

BACKGROUND: Among the treatments under investigation, various anti-tumour immunotherapies, in particular immune checkpoints inhibitors (ICI), currently exhibit the most promising preliminary results. First data from the phase II, randomized "IFCT MAPS-2", recently presented during the 2017 ASCO meeting, confirmed the value of ICI in MPM patients in cases of chemotherapy failure.

OUTLOOK AND CONCLUSIONS: However, several exciting immunotherapies other than ICI are presently being evaluated in MPM and are reported in this article. Moreover, many questions still need to be answered about immunotherapy: what is its potential value as first line treatment? How to target the best candidates for these treatments? Which combinations between immunotherapy and standard chemotherapy, targeted therapies, surgery or radiotherapy? Finally, it is now essential that every clinician has sufficient knowledge about the possible toxicities of immunotherapy.}, } @article {pmid29413505, year = {2018}, author = {Blyth, KG and Murphy, DJ}, title = {Progress and challenges in Mesothelioma: From bench to bedside.}, journal = {Respiratory medicine}, volume = {134}, number = {}, pages = {31-41}, doi = {10.1016/j.rmed.2017.11.015}, pmid = {29413505}, issn = {1532-3064}, support = {ETM/285/CSO_/Chief Scientist Office/United Kingdom ; }, mesh = {Biomarkers, Tumor/metabolism ; Biopsy ; Humans ; Lung Neoplasms/*diagnostic imaging/genetics/pathology/*therapy ; Magnetic Resonance Imaging ; Mesothelioma/*diagnostic imaging/genetics/pathology/*therapy ; Mesothelioma, Malignant ; Mutation ; Neoplasm Staging ; Positron Emission Tomography Computed Tomography ; Translational Research, Biomedical/methods/*trends ; }, abstract = {Malignant Pleural Mesothelioma (MPM) is currently an incurable cancer with a typical survival of 1 year from the time of diagnosis. The recent genomic and transcriptomic characterization of MPM presents new opportunities and challenges for MPM researchers. Recent advances in clinical and laboratory diagnostics, and proposals for an updated, data-driven, staging system, also present new challenges for clinicians and hospital services involved in MPM care. The aim of this review is first to introduce the reader to the topic of MPM, a disease that is causally linked to prior, typically occupational, exposure to asbestos fibres. Secondly, we will discuss MPM from the clinical and laboratory perspectives, including reviews of current and evolving therapies and our present understanding of the molecular basis of the disease. Finally, we will attempt to identify critical knowledge gaps that currently prevent more effective treatment, including the challenges involved in early detection and chemoprophylaxis.}, } @article {pmid29395477, year = {2018}, author = {Soloukey Tbalvandany, SS and Maat, AAPWM and Cornelissen, RR and Nuyttens, JJJME and Takkenberg, JJJM}, title = {WWW mesothelioma information: Surfing on unreliable waters. A cross-sectional study into the content and quality of online informational resources for mesothelioma patients.}, journal = {Patient education and counseling}, volume = {101}, number = {6}, pages = {1088-1094}, doi = {10.1016/j.pec.2018.01.009}, pmid = {29395477}, issn = {1873-5134}, mesh = {Benchmarking ; Consumer Health Information ; Cross-Sectional Studies ; Decision Making ; Humans ; Information Services/*standards ; *Information Storage and Retrieval ; *Internet ; Mesothelioma/*diagnosis/*therapy ; Netherlands ; Patients/*psychology ; }, abstract = {OBJECTIVE: Malignant Mesothelioma (MM) is a rare asbestos related disease mostly diagnosed in low-skilled patients. The decision-making process for MM treatment is complicated, making an adequate provision of information necessary. The objective of this study is to assess the content and quality of online informational resources available for Dutch MM patients.

METHODS: The first 100 hits of a Google search were studied using the JAMA benchmarks, the Modified Information Score (MIS) and the International Patient Decision Aid Standard Scoring (IPDAS).

RESULTS: A total of 37 sources were included. Six of the 37 resources were published by hospitals. On average, the informational resources scored 37 points on the MIS (scale 0-100). The resources from a (bio)medical sources scored the best on this scale. However, on the domain of use of language, these resources scored the worst.

CONCLUSIONS: The current level of medical content and quality of online informational resources for patient with MM is below average and cannot be used as decision-aids for patients.

PRACTICE IMPLICATIONS: The criteria used in this article could be used for future improvements of online informational resources for patients, both online, offline and through health education in the care path.}, } @article {pmid29387394, year = {2018}, author = {Tian, D and Wen, H and Brown, HE and Wang, X and Zhang, L and Fu, M}, title = {Multiple intracranial metastases from postoperative giant sarcomatoid malignant pleural mesothelioma: A case report and literature review.}, journal = {Molecular and clinical oncology}, volume = {8}, number = {1}, pages = {34-37}, pmid = {29387394}, issn = {2049-9450}, abstract = {Sarcomatoid malignant pleural mesothelioma (SMPM) is a rare tumor with poor response to treatment and a dismal prognosis. Distant metastases are not uncommon and usually appear at the late stages of the disease. However, cerebral metastases have rarely been documented. We herein report a case of a giant sarcomatoid carcinoma of the pleura in a 41-year-old male patient with no history of exposure to asbestos, who presented with a chief complaint of left-sided chest pain for 1 month. Extrapleural pneumonectomy and rib excision were performed. At 5 months after the surgery, the patient was diagnosed with multiple intracranial metastatic neoplasms and succumbed to the disease soon thereafter. The aim of the present case report was to emphasize this rare metastatic pattern and aggressive clinical course of SMPM, with a supplementary review of the previously published literature.}, } @article {pmid29386699, year = {2017}, author = {Cheng, YY and Mok, E and Tan, S and Leygo, C and McLaughlin, C and George, AM and Reid, G}, title = {SFRP Tumour Suppressor Genes Are Potential Plasma-Based Epigenetic Biomarkers for Malignant Pleural Mesothelioma.}, journal = {Disease markers}, volume = {2017}, number = {}, pages = {2536187}, pmid = {29386699}, issn = {1875-8630}, mesh = {Adaptor Proteins, Signal Transducing ; Asbestos/*toxicity ; Biomarkers, Tumor/blood/*genetics/metabolism ; Carcinogens/*toxicity ; Cell Line, Tumor ; DNA Methylation/drug effects ; Epigenesis, Genetic ; Eye Proteins/blood/*genetics/metabolism ; Humans ; Lung Neoplasms/blood/*genetics ; Membrane Proteins/blood/*genetics/metabolism ; Mesothelioma/blood/*genetics ; Mesothelioma, Malignant ; }, abstract = {Malignant pleural mesothelioma (MPM) is associated with asbestos exposure. Asbestos can induce chronic inflammation which in turn can lead to silencing of tumour suppressor genes. Wnt signaling pathway can be affected by chronic inflammation and is aberrantly activated in many cancers including colon and MPM. SFRP genes are antagonists of Wnt pathway, and SFRPs are potential tumour suppressors in colon, gastric, breast, ovarian, and lung cancers and mesothelioma. This study investigated the expression and DNA methylation of SFRP genes in MPM cells lines with and without demethylation treatment. Sixty-six patient FFPE samples were analysed and have showed methylation of SFRP2 (56%) and SFRP5 (70%) in MPM. SFRP2 and SFRP5 tumour-suppressive activity in eleven MPM lines was confirmed, and long-term asbestos exposure led to reduced expression of the SFRP1 and SFRP2 genes in the mesothelium (MeT-5A) via epigenetic alterations. Finally, DNA methylation of SFRPs is detectable in MPM patient plasma samples, with methylated SFRP2 and SFRP5 showing a tendency towards greater abundance in patients. These data suggested that SFRP genes have tumour-suppresive activity in MPM and that methylated DNA from SFRP gene promoters has the potential to serve as a biomarker for MPM patient plasma.}, } @article {pmid29375946, year = {2017}, author = {Arda, E and Arıkan, MG and Cetin, G and Kuyumcuoğlu, U and Usta, U}, title = {Malignant Mesothelioma of Tunica Vaginalis Testis: Macroscopic and Microscopic Features of a Very Rare Malignancy.}, journal = {Cureus}, volume = {9}, number = {11}, pages = {e1860}, pmid = {29375946}, issn = {2168-8184}, abstract = {Malignant mesothelioma of the tunica vaginalis testis (MMTVT) is an extremely rare tumour, usually mimicking benign pathologies of the scrotum. Our case is an 84-year-old male patient who appealed with a painless, left-sided scrotal swelling longer than 2 months. Although the level of tumour markers was normal, ultrasonographic examination results forced us to perform an inguinal scrotal exploration. Multiple small papillary tumours, both on tunica vaginalis and tunica albuginea, were detected intraoperatively. Due to these findings, radical orchiectomy was performed. A pathological evaluation showed malignant mesothelioma (MM) of the tunica vaginalis testis. Exposure to asbestos is a well-known risk factor. Furthermore, a history of trauma, herniorrhaphy and chronic hydroceles is blamed as a possible risk factor. Scrotal ultrasonography is the mainstay of primary diagnosis and, therefore, it should not be overlooked when dealing with benign scrotal cysts or hydroceles, which are very common pathologies at these decades, too. Radical inguinal orchiectomy is the primary treatment choice for localised MMTVT disease, whereas in signs of lymph node metastasis, inguinal lymph node dissection is required. Radical resection should be completed with chemotherapy and/or radiotherapy for an advanced or recurrent disease. This case, which is very rarely reported in the literature and detected during inguinal exploration, along with the pathological works that supported the diagnosis, was presented with this report.}, } @article {pmid29375377, year = {2017}, author = {Oien, DB and Garay, T and Eckstein, S and Chien, J}, title = {Cisplatin and Pemetrexed Activate AXL and AXL Inhibitor BGB324 Enhances Mesothelioma Cell Death from Chemotherapy.}, journal = {Frontiers in pharmacology}, volume = {8}, number = {}, pages = {970}, pmid = {29375377}, issn = {1663-9812}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; P30 CA168524/CA/NCI NIH HHS/United States ; P30 GM103326/GM/NIGMS NIH HHS/United States ; }, abstract = {Reactive oxygen species (ROS) can promote or inhibit tumorigenesis. In mesothelioma, asbestos exposure to serous membranes induces ROS through iron content and chronic inflammation, and ROS promote cell survival signaling in mesothelioma. Moreover, a current chemotherapy regimen for mesothelioma consisting of a platinum and antifolate agent combination also induce ROS. Mesothelioma is notoriously chemotherapy-resistant, and we propose that ROS induced by cisplatin and pemetrexed may promote cell survival signaling pathways, which ultimately may contribute to chemotherapy resistance. In The Cancer Genome Atlas datasets, we found AXL kinase expression is relatively high in mesothelioma compared to other cancer samples. We showed that ROS induce the phosphorylation of AXL, which was blocked by the selective inhibitor BGB324 in VMC40 and P31 mesothelioma cells. We also showed that cisplatin and pemetrexed induce the phosphorylation of AXL and Akt, which was also blocked by BGB324 as well as by N-acetylcysteine antioxidant. AXL knockdown in these cells enhances sensitivity to cisplatin and pemetrexed. Similarly, AXL inhibitor BGB324 also enhances sensitivity to cisplatin and pemetrexed. Finally, higher synergy was observed when cells were pretreated with BGB324 before adding chemotherapy. These results demonstrate cisplatin and pemetrexed induce ROS that activate AXL, and blocking AXL activation enhances the efficacy of cisplatin and pemetrexed. These results suggest AXL inhibition combined with the current chemotherapy regimen may represent an effective strategy to enhance the efficacy of chemotherapy in mesothelioma. This is the first study, to our knowledge, on chemotherapy-induced activation of AXL and cell survival pathways associated with ROS signaling.}, } @article {pmid29371938, year = {2017}, author = {Hylebos, M and Van Camp, G and Vandeweyer, G and Fransen, E and Beyens, M and Cornelissen, R and Suls, A and Pauwels, P and van Meerbeeck, JP and Op de Beeck, K}, title = {Large-scale copy number analysis reveals variations in genes not previously associated with malignant pleural mesothelioma.}, journal = {Oncotarget}, volume = {8}, number = {69}, pages = {113673-113686}, pmid = {29371938}, issn = {1949-2553}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive tumor that is often causally associated with asbestos exposure. Comparative genomic hybridization techniques and arrays demonstrated a complex set of copy number variations (CNVs) in the MPM-genome. These techniques however have a limited resolution, throughput and flexibility compared to next-generation sequencing platforms. In this study, the presence of CNVs in the MPM-genome was investigated using an MPM-cohort (N = 85) for which genomic microarray data are available through 'The Cancer Genome Atlas' (TCGA). To validate these results, the genomes of MPMs and matched normal samples (N = 21) were analyzed using low-pass whole genome sequencing on an 'Illumina HiSeq' platform. CNVs were detected using in-house developed analysis pipelines and frequencies of copy number loss and gain were calculated. In both datasets, losses on chromosomes 1, 3, 4, 6, 9, 13 and 22 and gains on chromosomes 1, 5, 7 and 17 were found in at least 25% and 15% of MPMs, respectively. Besides the well-known MPM-associated genes, CDKN2A, NF2 and BAP1, other interesting cancer-associated genes were listed as frequently involved in a copy number loss (e.g. EP300, SETD2 and PBRM1). Moreover, four cancer-associated genes showed a high frequency of copy number gain in both datasets (i.e. TERT, FCGR2B, CD79B and PRKAR1A). A statistically significant association between overall survival and the presence of copy number loss in the CDKN2A-containing region was observed in the TCGA-set. In conclusion, recurrent CNVs were detected in both datasets, occurring in regions harboring known MPM-associated genes and genes not previously linked to MPM.}, } @article {pmid29342862, year = {2018}, author = {Tolani, B and Acevedo, LA and Hoang, NT and He, B}, title = {Heterogeneous Contributing Factors in MPM Disease Development and Progression: Biological Advances and Clinical Implications.}, journal = {International journal of molecular sciences}, volume = {19}, number = {1}, pages = {}, pmid = {29342862}, issn = {1422-0067}, mesh = {*Disease Progression ; Genes, Tumor Suppressor ; Genome ; Humans ; Lung Neoplasms/genetics/immunology/*pathology ; Mesothelioma/genetics/immunology/*pathology ; Mesothelioma, Malignant ; Pleural Neoplasms/genetics/immunology/*pathology ; Tumor Microenvironment ; }, abstract = {Malignant pleural mesothelioma (MPM) tumors are remarkably aggressive and most patients only survive for 5-12 months; irrespective of stage; after primary symptoms appear. Compounding matters is that MPM remains unresponsive to conventional standards of care; including radiation and chemotherapy. Currently; instead of relying on molecular signatures and histological typing; MPM treatment options are guided by clinical stage and patient characteristics because the mechanism of carcinogenesis has not been fully elucidated; although about 80% of cases can be linked to asbestos exposure. Several molecular pathways have been implicated in the MPM tumor microenvironment; such as angiogenesis; apoptosis; cell-cycle regulation and several growth factor-related pathways predicted to be amenable to therapeutic intervention. Furthermore, the availability of genomic data has improved our understanding of the pathobiology of MPM. The MPM genomic landscape is dominated by inactivating mutations in several tumor suppressor genes; such as CDKN2A; BAP1 and NF2. Given the complex heterogeneity of the tumor microenvironment in MPM; a better understanding of the interplay between stromal; endothelial and immune cells at the molecular level is required; to chaperone the development of improved personalized therapeutics. Many recent advances at the molecular level have been reported and several exciting new treatment options are under investigation. Here; we review the challenges and the most up-to-date biological advances in MPM pertaining to the molecular pathways implicated; progress at the genomic level; immunological progression of this fatal disease; and its link with developmental cell pathways; with an emphasis on prognostic and therapeutic treatment strategies.}, } @article {pmid29338319, year = {2018}, author = {Matboli, M and Shafei, AE and Azazy, AE and Reda, M and El-Khazragy, N and Nagy, AA and Ali, MA and Sobhi, M and Abdel-Rahman, O}, title = {Clinical evaluation of circulating miR-548a-3p and -20a expression in malignant pleural mesothelioma patients.}, journal = {Biomarkers in medicine}, volume = {12}, number = {2}, pages = {129-139}, doi = {10.2217/bmm-2017-0224}, pmid = {29338319}, issn = {1752-0371}, mesh = {Adult ; Aged ; Area Under Curve ; Asbestos/toxicity ; Biomarkers, Tumor/blood ; Environmental Exposure ; Female ; Humans ; Lung Neoplasms/*diagnosis/genetics/pathology ; Male ; Mesothelioma/*diagnosis/genetics/pathology ; Mesothelioma, Malignant ; MicroRNAs/*blood/genetics/metabolism ; Middle Aged ; ROC Curve ; Real-Time Polymerase Chain Reaction ; Sensitivity and Specificity ; Smoking ; }, abstract = {AIM: miRNAs may act as promising diagnostic and prognostic biomarkers of mesothelioma. This study integrates serum miR-548a-3p and miR-20a expression based on in silico data analysis followed by clinical validation in malignant mesothelioma patients (malignant pleural mesothelioma [MPM]).

PATIENTS & METHODS: Serum miR-548a-3p and  miR-20a level was assessed in the serum of patients with MPM, chronic asbestos exposure and healthy volunteers by quantitative real-time PCR.

RESULTS: The expression of serum miR-548a-3p and  miR-20a was positive in 91.6 and 96.7% MPM patients, respectively. Both miRNAs were able to segregate between cases and controls. The sensitivity of the combined chosen serum miRNAs reached 100% in the diagnosis of MPM.

CONCLUSION: The current work revealed that sera miR-548a-3p and miR-20a may serve as promising novel diagnostic tools for MPM.}, } @article {pmid29337930, year = {2018}, author = {Baur, X}, title = {Asbestos-Related Disorders in Germany: Background, Politics, Incidence, Diagnostics and Compensation.}, journal = {International journal of environmental research and public health}, volume = {15}, number = {1}, pages = {}, pmid = {29337930}, issn = {1660-4601}, mesh = {Asbestos/*toxicity ; Compensation and Redress ; Germany/epidemiology ; Humans ; Incidence ; Occupational Diseases/*chemically induced/diagnosis/economics/epidemiology ; Occupational Exposure/*adverse effects/economics/legislation & jurisprudence ; Politics ; }, abstract = {There was some limited use of asbestos at end of the 19th century in industrialized countries including Germany, but its consumption dramatically increased after World War II. The increase in use and exposure was followed by the discovery of high numbers of asbestos-related diseases with a mean latency period of about 38 years in Germany. The strong socio-political pressure from the asbestos industry, its affiliated scientists and physicians has successfully hindered regulatory measures and an asbestos ban for many years; a restrictive stance that is still being unravelled in compensation litigation. This national experience is compared with the situation in other industrialized countries and against the backdrop of the constant efforts of the WHO to eliminate asbestos-related diseases worldwide.}, } @article {pmid29320538, year = {2018}, author = {Patch, AM and Nones, K and Kazakoff, SH and Newell, F and Wood, S and Leonard, C and Holmes, O and Xu, Q and Addala, V and Creaney, J and Robinson, BW and Fu, S and Geng, C and Li, T and Zhang, W and Liang, X and Rao, J and Wang, J and Tian, M and Zhao, Y and Teng, F and Gou, H and Yang, B and Jiang, H and Mu, F and Pearson, JV and Waddell, N}, title = {Germline and somatic variant identification using BGISEQ-500 and HiSeq X Ten whole genome sequencing.}, journal = {PloS one}, volume = {13}, number = {1}, pages = {e0190264}, pmid = {29320538}, issn = {1932-6203}, mesh = {*Genome, Human ; *Germ Cells ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; INDEL Mutation ; Polymorphism, Single Nucleotide ; }, abstract = {Technological innovation and increased affordability have contributed to the widespread adoption of genome sequencing technologies in biomedical research. In particular large cancer research consortia have embraced next generation sequencing, and have used the technology to define the somatic mutation landscape of multiple cancer types. These studies have primarily utilised the Illumina HiSeq platforms. In this study we performed whole genome sequencing of three malignant pleural mesothelioma and matched normal samples using a new platform, the BGISEQ-500, and compared the results obtained with Illumina HiSeq X Ten. Germline and somatic, single nucleotide variants and small insertions or deletions were independently identified from data aligned human genome reference. The BGISEQ-500 and HiSeq X Ten platforms showed high concordance for germline calls with genotypes from SNP arrays (>99%). The germline and somatic single nucleotide variants identified in both sequencing platforms were highly concordant (86% and 72% respectively). These results indicate the potential applicability of the BGISEQ-500 platform for the identification of somatic and germline single nucleotide variants by whole genome sequencing. The BGISEQ-500 datasets described here represent the first publicly-available cancer genome sequencing performed using this platform.}, } @article {pmid29316066, year = {2018}, author = {Kimura, N and Hasegawa, M and Hiroshima, K}, title = {SMARCB1/INI1/BAF47- deficient pleural malignant mesothelioma with rhabdoid features.}, journal = {Pathology international}, volume = {68}, number = {2}, pages = {128-132}, doi = {10.1111/pin.12623}, pmid = {29316066}, issn = {1440-1827}, mesh = {Biomarkers, Tumor/metabolism ; Humans ; Lung Neoplasms/*metabolism/pathology ; Male ; Mesothelioma/metabolism/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Rhabdoid Tumor/metabolism/*pathology ; SMARCB1 Protein/*deficiency ; Tumor Suppressor Proteins/deficiency ; Ubiquitin Thiolesterase/deficiency ; }, abstract = {Malignant mesothelioma (MM) with rhabdoid features is an MM variant. Fifteen cases have been reported previously, all of which were combined with other types of MM. Herein, we report an autopsy case of pleural MM with monomorphic rhabdoid features. The patient was a 62-year-old male without a history of asbestos exposure. An autopsy revealed a soft, granular tumor that replaced the entire left pleura and had invaded to the diaphragm and lower lobe of the lung. The tumor cells, which had eosinophilic plump cytoplasm and eccentric nuclei, were loosely cohesive. Immunohistochemistry showed that the cells were diffusely positive for calretinin, D2-40, vimentin, CAM5.2, and AE1/AE3; and negative for WT-1, TTF-1, CK7, CEA, desmin, CD34, BCL-2, S100 protein, and p40. Neither homozygous deletion of p16 nor BAP-1 protein loss was observed. Loss of INI1/BAF47 protein, an indicator of malignant rhabdoid tumor, was observed. Therefore, MM with rhabdoid features was confirmed.}, } @article {pmid29306869, year = {2018}, author = {Solbes, E and Harper, RW}, title = {Biological responses to asbestos inhalation and pathogenesis of asbestos-related benign and malignant disease.}, journal = {Journal of investigative medicine : the official publication of the American Federation for Clinical Research}, volume = {66}, number = {4}, pages = {721-727}, doi = {10.1136/jim-2017-000628}, pmid = {29306869}, issn = {1708-8267}, mesh = {Asbestos/*adverse effects ; Humans ; *Inhalation Exposure ; Lung Diseases/diagnosis/etiology ; Mass Screening ; Risk Factors ; }, abstract = {Asbestos comprises a group of fibrous minerals that are naturally occurring in the environment. Because of its natural properties, asbestos gained popularity for commercial applications in the late 19th century and was used throughout the majority of the 20th century, with predominant use in the construction, automotive, and shipbuilding industries. Asbestos has been linked to a spectrum of pulmonary diseases, such as pleural fibrosis and plaques, asbestosis, benign asbestos pleural effusion, small cell lung carcinoma, non-small cell lung carcinoma, and malignant mesothelioma. There are several mechanisms through which asbestos can lead to both benign and malignant disease, and they include alterations at the chromosomal level, activation of oncogenes, loss of tumor suppressor genes, alterations in cellular signal transduction pathways, generation of reactive oxygen and nitrogen species, and direct mechanical damage to cells from asbestos fibers. While known risk factors exist for the development of asbestos-related malignancies, there are currently no effective means to determine which asbestos-exposed patients will develop malignancy and which will not. There are also no established screening strategies to detect asbestos-related malignancies in patients who have a history of asbestos exposure. In this article, we present a case that highlights the different biological responses in human hosts to asbestos exposure.}, } @article {pmid29303291, year = {2018}, author = {Kolek, V}, title = {[Malign pleural mesothelioma - so far an undefeated tumor].}, journal = {Vnitrni lekarstvi}, volume = {63}, number = {11}, pages = {884-888}, pmid = {29303291}, issn = {0042-773X}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Combined Modality Therapy ; Humans ; Immunotherapy/methods ; *Lung Neoplasms/diagnosis/therapy ; *Mesothelioma/diagnosis/therapy ; Mesothelioma, Malignant ; *Pleural Neoplasms/diagnosis/therapy ; Pneumonectomy/methods ; }, abstract = {Malign pleural mesothelioma is the most frequent primary tumor of the pleura of high aggressiveness. Its most frequent cause is contact with asbestos and, although working with asbestos is already prohibited in developed countries, its incidence is on the increase so far. Diagnostics primarily considers anamnesis, clinical symptoms and immunohistochemical examination of a tumor sample. The basic therapy used over the past 10 years is chemotherapy with cisplatin - pemetrexed combinations. Numerous studies are going on with a different biologically targeted therapy, immunotherapy and other drugs which may improve patients prognosis. The surgical approach is limited by a suitable choice of patients and sufficient experience of the medical center. Extrapleural pneumonectomy or extended pleurectomy are performed. However even the combined therapy with adjuvant or neoadjuvant chemotherapy or radiotherapy has not considerably extended survival.Key words: diagnostics - epidemiology - malign pleural mesothelioma - therapy.}, } @article {pmid29298805, year = {2018}, author = {}, title = {Correction: Germline BAP1 Mutational Landscape of Asbestos-Exposed Malignant Mesothelioma Patients with Family History of Cancer.}, journal = {Cancer research}, volume = {78}, number = {1}, pages = {309}, doi = {10.1158/0008-5472.CAN-17-3445}, pmid = {29298805}, issn = {1538-7445}, } @article {pmid29298350, year = {2018}, author = {Tatsuta, T and Satoh, T and Sugawara, S and Hara, A and Hosono, M}, title = {Sialic acid-binding lectin from bullfrog eggs inhibits human malignant mesothelioma cell growth in vitro and in vivo.}, journal = {PloS one}, volume = {13}, number = {1}, pages = {e0190653}, pmid = {29298350}, issn = {1932-6203}, mesh = {Amphibian Proteins/isolation & purification/*pharmacology ; Animals ; Apoptosis/drug effects ; Cell Line, Tumor ; Cell Proliferation/*drug effects ; Drug Synergism ; Female ; Humans ; In Vitro Techniques ; Lectins/isolation & purification/*pharmacology ; Male ; Mesothelioma/*pathology ; Mice, Inbred BALB C ; Mice, Nude ; Ovum/*chemistry ; Pemetrexed/administration & dosage ; Rana catesbeiana ; Ribonucleases/isolation & purification/*pharmacology ; Weight Loss/drug effects ; Xenograft Model Antitumor Assays ; }, abstract = {Malignant mesothelioma is an aggressive cancer that results from exposure to asbestos. The therapeutic options for this type of cancer are limited; therefore, the development of novel therapeutic agents is urgently required. Sialic acid-binding lectin isolated from Rana catesbeiana oocytes (cSBL) is a novel therapeutic candidate for cancer, which exhibits antitumor activity mediated through RNA degradation. In the present study, we evaluated the effect of cSBL in vitro and in vivo. Xenograft-competent H2452 and MSTO human mesothelioma cell lines were treated with cSBL, and the pathway by which cSBL induces apoptosis was analyzed. In vivo studies were performed using nude mice inoculated with one of the two cell lines, and the effects of cSBL and pemetrexed were monitored simultaneously. Furthermore, the pharmacological interactions between the three agents (pemetrexed, cisplatin and cSBL) were statistically assessed. It was demonstrated that cSBL treatments caused morphological and biochemical apoptotic changes in both cell lines. Caspase cascade analysis revealed that an intrinsic pathway mediated cSBL-induced apoptosis. The administration of cSBL significantly inhibited tumor growth in two xenograft models, without any adverse effects. Furthermore, the combination index and dose reduction index values indicated that the cSBL + pemetrexed combination showed the highest synergism, and thus potential for reducing dosage of each drug, compared with the other combinations, including the existing pemetrexed + cisplatin regimen. cSBL exerted prominent antitumor effects on malignant mesothelioma cells in vitro and in vivo, and showed favorable effects when combined with pemetrexed. These results suggest that cSBL has potential as a novel drug for the treatment of malignant mesothelioma.}, } @article {pmid29296529, year = {2017}, author = {Schürch, CM and Forster, S and Brühl, F and Yang, SH and Felley-Bosco, E and Hewer, E}, title = {The "don't eat me" signal CD47 is a novel diagnostic biomarker and potential therapeutic target for diffuse malignant mesothelioma.}, journal = {Oncoimmunology}, volume = {7}, number = {1}, pages = {e1373235}, pmid = {29296529}, issn = {2162-4011}, abstract = {Diffuse malignant mesothelioma (DMM) is one of the prognostically most discouraging cancers with median survivals of only 12-22 months. Due to its insidious onset and delayed detection, DMM is often at an advanced stage at diagnosis and is considered incurable. Combined chemo- and radiotherapy followed by surgery only marginally affect outcome at the cost of significant morbidity. Because of the long time period between exposure to asbestos and disease onset, the incidence of DMM is still rising and predicted to peak around 2020. Novel markers for the reliable diagnosis of DMM in body cavity effusion specimens as well as more effective, targeted therapies are urgently needed. Here, we show that the "don't eat me" signalling molecule CD47, which inhibits phagocytosis by binding to signal regulatory protein α on macrophages, is overexpressed in DMM cells. A two-marker panel of high CD47 expression and BRCA1-associated protein 1 (BAP-1) deficiency had a sensitivity of 78% and specificity of 100% in discriminating DMM tumour cells from reactive mesothelial cells in effusions, which is superior to the currently used four-marker combination of BAP-1, glucose transporter type 1, epithelial membrane antigen and desmin. In addition, blocking CD47 inhibited growth and promoted phagocytosis of DMM cell lines by macrophages in vitro. Furthermore, DMM tumours in surgical specimens from patients as well as in a mouse DMM model expressed high levels of CD47 and were heavily infiltrated by macrophages. Our study demonstrates that CD47 is an accurate novel diagnostic DMM biomarker and that blocking CD47 may represent a promising therapeutic strategy for DMM.}, } @article {pmid29289945, year = {2018}, author = {Finkelstein, MM}, title = {Reanalysis of non-occupational exposure to asbestos and the risk of pleural mesothelioma.}, journal = {Occupational and environmental medicine}, volume = {75}, number = {6}, pages = {472-473}, doi = {10.1136/oemed-2017-104783}, pmid = {29289945}, issn = {1470-7926}, mesh = {*Asbestos ; Humans ; *Lung Neoplasms ; *Mesothelioma ; *Pleural Neoplasms ; }, } @article {pmid29284684, year = {2017}, author = {Carder, M and Darnton, A and Gittins, M and Stocks, SJ and Ross, D and Barber, CM and Agius, RM}, title = {Chest physician-reported, work-related, long-latency respiratory disease in Great Britain.}, journal = {The European respiratory journal}, volume = {50}, number = {6}, pages = {}, doi = {10.1183/13993003.00961-2017}, pmid = {29284684}, issn = {1399-3003}, mesh = {Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Asbestos/toxicity ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Occupational Diseases/*chemically induced/*epidemiology ; *Occupational Exposure ; Physicians ; Respiration Disorders/*chemically induced/*epidemiology ; Sex Distribution ; Silicon Dioxide/toxicity ; United Kingdom/epidemiology ; Young Adult ; }, abstract = {Much of the current burden of long-latency respiratory disease (LLRD) in Great Britain is attributed to historical asbestos exposure. However, continuing exposure to other agents, notably silica, also contributes to disease burden. The aim of this study was to investigate the incidence of work-related LLRD reported by chest physicians in Great Britain, including variations by age, gender, occupation and suspected agent.LLRD incidence and incidence rate ratios by occupation were estimated (1996-2014). Mesothelioma cases by occupation were compared with proportional mortality ratios.Cases were predominantly in men (95%) and 92% of all cases were attributed to asbestos. Annual average incidence rates (males) per 100 000 were: benign pleural disease, 7.1 (95% CI 6.0-8.2); mesothelioma, 5.4 (4.8-6.0); pneumoconiosis, 1.9 (1.7-2.2); lung cancer, 0.8 (0.6-1.0); chronic obstructive pulmonary disease (COPD), 0.3 (0.2-0.4). Occupations with a particularly high incidence of LLRD were miners and quarrymen (COPD), plumbers and gas fitters (asbestosis), and shipyard and dock workers (all other categories). There was a clear concordance between cases of SWORD mesothelioma and proportional mortality ratios by occupation.Occupationally caused LLRD continues to contribute to a significant disease burden. Many cases are attributable to past exposure to agents such as asbestos and silica, but the potential for occupational exposures persists.}, } @article {pmid29279043, year = {2018}, author = {Yanamala, N and Kisin, ER and Gutkin, DW and Shurin, MR and Harper, M and Shvedova, AA}, title = {Characterization of pulmonary responses in mice to asbestos/asbestiform fibers using gene expression profiles.}, journal = {Journal of toxicology and environmental health. Part A}, volume = {81}, number = {4}, pages = {60-79}, doi = {10.1080/15287394.2017.1408201}, pmid = {29279043}, issn = {1528-7394}, mesh = {Animals ; Asbestos, Amphibole/*toxicity ; Asbestos, Crocidolite/*toxicity ; Calcium Compounds/*toxicity ; Female ; Inflammation/chemically induced ; Lung/*drug effects/immunology/pathology ; Mice ; Mice, Inbred C57BL ; Silicates/*toxicity ; Transcriptome/*drug effects ; Zeolites/*toxicity ; }, abstract = {Humans exposed to asbestos and/or asbestiform fibers are at high risk of developing many lung diseases including asbestosis, lung cancer, and malignant mesothelioma. However, the disease-causing potential and specific metabolic mechanisms and pathways associated with various asbestos/asbestiform fiber exposures triggering different carcinogenic and non-carcinogenic outcomes are still largely unknown. The aim of this this study was to investigate gene expression profiles and inflammatory responses to different asbestos/asbestiform fibers at the acute/sub-acute phase that may be related to delayed pathological outcomes observed at later time points. Mice were exposed to asbestos (crocidolite, tremolite asbestos), asbestiform fibers (erionite), and a low pathogenicity mineral fiber (wollastonite) using oropharyngeal aspiration. Similarities in inflammatory and tissue damage responses, albeit with quantitative differences, were observed at day 1 and 7 post treatment. Exposure to different fibers induced significant changes in regulation and release of a number of inflammatory cytokines/chemokines. Comparative analysis of changes in gene regulation in the lung on day 7 post exposure were interpretable in the context of differential biological responses that were consistent with histopathological findings at days 7 and 56 post treatment. Our results noted differences in the magnitudes of pulmonary responses and gene regulation consistent with pathological alterations induced by exposures to four asbestos/asbestiform fibers examined. Further comparative mechanistic studies linking early responses with the long-term endpoints may be instrumental to understanding triggering mechanisms underlying pulmonary carcinogenesis, that is lung cancer versus mesothelioma.}, } @article {pmid29277245, year = {2018}, author = {Tranchant, R and Montagne, F and Jaurand, MC and Jean, D}, title = {[Molecular heterogeneity of malignant pleural mesotheliomas].}, journal = {Bulletin du cancer}, volume = {105}, number = {1}, pages = {35-45}, doi = {10.1016/j.bulcan.2017.11.007}, pmid = {29277245}, issn = {1769-6917}, mesh = {Asbestos/toxicity ; Carcinogens/toxicity ; Chromosome Aberrations ; Epigenesis, Genetic ; Humans ; Lung Neoplasms/classification/etiology/*genetics/therapy ; Mesothelioma/classification/etiology/*genetics/therapy ; Mesothelioma, Malignant ; Pleural Neoplasms/classification/etiology/*genetics/therapy ; Prognosis ; Transcription, Genetic ; }, abstract = {Malignant pleural mesothelioma (MPM) is predominantly an occupational cancer, most often linked to asbestos exposure. Malignant pleural mesothelioma prognosis is poor with a short survival median, due to the aggressiveness of tumor cells and the weak efficiency of conventional anti-cancer therapies. Clinical, histological, and molecular data suggest tumor heterogeneity between patients as it was also shown for other cancer types. Consequently, there is an urgent need to develop new therapies that take into account this heterogeneity and the molecular characteristics of malignant pleural mesothelioma, in particular by identifying new anti-cancer drugs targeting the molecular specificities of each malignant pleural mesothelioma. Malignant pleural mesothelioma is characterized by numerous molecular alterations at the chromosomal, genetic and epigenetic levels. Molecular classification based on gene expression profile has firstly defined two tumor groups, C1 and C2, and more recently, four groups. By integrating genetic and transcriptomic analysis, a C2[LN] tumor subgroup of the C2 group has been identified and characterized. In addition to tumor heterogeneity between patients, intra-tumor heterogeneity is supported by several evidences. Most therapeutic strategies that take into account the tumor molecular characteristics have focused on targeted therapies based on mutated genes. A more appropriate strategy would be to consider better-defined tumor groups on the basis of several molecular alterations types as it has been proposed for the C2[LN] subgroup. A robust definition of homogeneous tumor groups sharing common molecular characteristics is necessary for the development of effective precision medicine for malignant pleural mesothelioma.}, } @article {pmid29269588, year = {2017}, author = {Feder, IS and Tischoff, I and Theile, A and Schmitz, I and Merget, R and Tannapfel, A}, title = {Correspondence regarding the article "The asbestos fibre burden in human lungs: new insights into the chrysotile debate".}, journal = {The European respiratory journal}, volume = {50}, number = {6}, pages = {}, doi = {10.1183/13993003.02204-2017}, pmid = {29269588}, issn = {1399-3003}, mesh = {*Asbestos ; *Asbestos, Serpentine ; Humans ; Lung ; Lung Neoplasms ; Mesothelioma ; }, } @article {pmid29269586, year = {2017}, author = {Sartorelli, P}, title = {Correspondence regarding the article "The asbestos fibre burden in human lungs: new insights into the chrysotile debate".}, journal = {The European respiratory journal}, volume = {50}, number = {6}, pages = {}, doi = {10.1183/13993003.02188-2017}, pmid = {29269586}, issn = {1399-3003}, mesh = {*Asbestos ; *Asbestos, Serpentine ; Humans ; Lung ; Lung Neoplasms ; Mesothelioma ; }, } @article {pmid29269580, year = {2017}, author = {Oliver, LC and Belpoggi, F and Budnik, LT and Egilman, D and Frank, AL and Mandrioli, D and Soskolne, CL and Terracini, B and Welch, L and Baur, X}, title = {Correspondence regarding the article "The asbestos fibre burden in human lungs: new insights into the chrysotile debate".}, journal = {The European respiratory journal}, volume = {50}, number = {6}, pages = {}, doi = {10.1183/13993003.01644-2017}, pmid = {29269580}, issn = {1399-3003}, mesh = {*Asbestos ; *Asbestos, Serpentine ; Humans ; Lung ; Lung Neoplasms ; Mesothelioma ; }, } @article {pmid29269578, year = {2017}, author = {Lamote, K and Vynck, M and Thas, O and Van Cleemput, J and Nackaerts, K and van Meerbeeck, JP}, title = {Exhaled breath to screen for malignant pleural mesothelioma: a validation study.}, journal = {The European respiratory journal}, volume = {50}, number = {6}, pages = {}, doi = {10.1183/13993003.00919-2017}, pmid = {29269578}, issn = {1399-3003}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Belgium ; *Breath Tests ; Case-Control Studies ; Cross-Sectional Studies ; Exhalation ; Female ; Humans ; Logistic Models ; Lung Neoplasms/*diagnosis ; Male ; Mesothelioma/*diagnosis ; Middle Aged ; Pleural Neoplasms/*diagnosis ; ROC Curve ; Volatile Organic Compounds/analysis ; }, abstract = {Malignant pleural mesothelioma (MPM) is predominantly caused by asbestos exposure and has a poor prognosis. Breath contains volatile organic compounds (VOCs) and can be explored as an early detection tool. Previously, we used multicapillary column/ion mobility spectrometry (MCC/IMS) to discriminate between patients with MPM and asymptomatic high-risk persons with a high rate of accuracy. Here, we aim to validate these findings in different control groups.Breath and background samples were obtained from 52 patients with MPM, 52 healthy controls without asbestos exposure (HC), 59 asymptomatic former asbestos workers (AEx), 41 patients with benign asbestos-related diseases (ARD), 70 patients with benign non-asbestos-related lung diseases (BLD) and 56 patients with lung cancer (LC).After background correction, logistic lasso regression and receiver operating characteristic (ROC) analysis, the MPM group was discriminated from the HC, AEx, ARD, BLD and LC groups with 65%, 88%, 82%, 80% and 72% accuracy, respectively. Combining AEx and ARD patients resulted in 94% sensitivity and 96% negative predictive value (NPV). The most important VOCs selected were P1, P3, P7, P9, P21 and P26.We discriminated MPM patients from at-risk subjects with great accuracy. The high sensitivity and NPV allow breath analysis to be used as a screening tool for ruling out MPM.}, } @article {pmid29269563, year = {2018}, author = {Marinaccio, A and Corfiati, M and Binazzi, A and Di Marzio, D and Scarselli, A and Ferrante, P and Bonafede, M and Verardo, M and Mirabelli, D and Gennaro, V and Mensi, C and Schallemberg, G and Mazzoleni, G and Merler, E and Girardi, P and Negro, C and D'Agostin, F and Romanelli, A and Chellini, E and Silvestri, S and Pascucci, C and Calisti, R and Stracci, F and Romeo, E and Ascoli, V and Trafficante, L and Carrozza, F and Angelillo, IF and Cavone, D and Cauzillo, G and Tallarigo, F and Tumino, R and Melis, M and Iavicoli, S and , }, title = {The epidemiology of malignant mesothelioma in women: gender differences and modalities of asbestos exposure.}, journal = {Occupational and environmental medicine}, volume = {75}, number = {4}, pages = {254-262}, pmid = {29269563}, issn = {1470-7926}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Female ; Humans ; Italy/epidemiology ; Lung Neoplasms/chemically induced/*epidemiology ; Male ; Mesothelioma/chemically induced/*epidemiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/*adverse effects/statistics & numerical data ; Registries ; Risk Factors ; Sex Factors ; }, abstract = {INTRODUCTION: The epidemiology of gender differences for mesothelioma incidence has been rarely discussed in national case lists. In Italy an epidemiological surveillance system (ReNaM) is working by the means of a national register.

METHODS: Incident malignant mesothelioma (MM) cases in the period 1993 to 2012 were retrieved from ReNaM. Gender ratio by age class, period of diagnosis, diagnostic certainty, morphology and modalities of asbestos exposure has been analysed using exact tests for proportion. Economic activity sectors, jobs and territorial distribution of mesothelioma cases in women have been described and discussed. To perform international comparative analyses, the gender ratio of mesothelioma deaths was calculated by country from the WHO database and the correlation with the mortality rates estimated.

RESULTS: In the period of study a case list of 21 463 MMs has been registered and the modalities of asbestos exposure have been investigated for 16 458 (76.7%) of them. The gender ratio (F/M) was 0.38 and 0.70 (0.14 and 0.30 for occupationally exposed subjects only) for pleural and peritoneal cases respectively. Occupational exposures for female MM cases occurred in the chemical and plastic industry, and mainly in the non-asbestos textile sector. Gender ratio proved to be inversely correlated with mortality rate among countries.

CONCLUSIONS: The consistent proportion of mesothelioma cases in women in Italy is mainly due to the relevant role of non-occupational asbestos exposures and the historical presence of the female workforce in several industrial settings. Enhancing the awareness of mesothelioma aetiology in women could support the effectiveness of welfare system and prevention policies.}, } @article {pmid29265930, year = {2018}, author = {Crovella, S and Moura, RR and Cappellani, S and Celsi, F and Trevisan, E and Schneider, M and Brollo, A and Nicastro, EM and Vita, F and Finotto, L and Zabucchi, G and Borelli, V}, title = {A genetic variant of NLRP1 gene is associated with asbestos body burden in patients with malignant pleural mesothelioma.}, journal = {Journal of toxicology and environmental health. Part A}, volume = {81}, number = {5}, pages = {98-105}, doi = {10.1080/15287394.2017.1416911}, pmid = {29265930}, issn = {1528-7394}, mesh = {Adaptor Proteins, Signal Transducing/*genetics/metabolism ; Aged ; Aged, 80 and over ; Apoptosis Regulatory Proteins/*genetics/metabolism ; Asbestos/*toxicity ; Body Burden ; Female ; Genetic Variation ; Humans ; Italy ; Lung/drug effects/*pathology ; Lung Neoplasms/*genetics/metabolism ; Male ; Mesothelioma/*genetics/metabolism ; Mesothelioma, Malignant ; Middle Aged ; NLR Proteins ; Occupational Exposure/*adverse effects ; }, abstract = {The presence of asbestos bodies (ABs) in lung parenchyma is considered a histopathologic hallmark of past exposure to asbestos fibers, of which there was a population of longer fibers. The mechanisms underlying AB formation are complex, involving inflammatory responses and iron (Fe) metabolism. Thus, the responsiveness to AB formation is variable, with some individuals appearing to be poor AB formers. The aim of this study was to disclose the possible role of genetic variants of genes encoding inflammasome and iron metabolism proteins in the ability to form ABs in a population of 81 individuals from North East Italy, who died after having developed malignant pleural mesothelioma (MPM). This study included 86 genetic variants distributed in 10 genes involved in Fe metabolism and 7 genetic variants in two genes encoding for inflammasome molecules. Genotypes/haplotypes were compared according to the number of lung ABs. Data showed that the NLRP1 rs12150220 missense variant (H155L) was significantly correlated with numbers of ABs in MPM patients. Specifically, a low number of ABs was detected in individuals carrying the NLRP1 rs12150220 A/T genotype. Our findings suggest that the NLRP1 inflammasome might contribute in the development of lung ABs. It is postulated that the NLRP1 missense variant may be considered as one of the possible host genetic factors contributing to individual variability in coating efficiency, which needs to be taken when assessing occupational exposure to asbestos.}, } @article {pmid29260910, year = {2018}, author = {Khella, MS and Salem, AM and Abdel-Rahman, O and Saad, AS}, title = {The Association Between the FTO rs9939609 Variant and Malignant Pleural Mesothelioma Risk: A Case-Control Study.}, journal = {Genetic testing and molecular biomarkers}, volume = {22}, number = {2}, pages = {79-84}, doi = {10.1089/gtmb.2017.0146}, pmid = {29260910}, issn = {1945-0257}, mesh = {Adult ; Aged ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO/*genetics ; Case-Control Studies ; Female ; Humans ; Male ; Mesothelioma/*genetics/pathology ; Middle Aged ; Pleural Neoplasms/*genetics/pathology ; *Polymorphism, Genetic ; Risk ; Young Adult ; }, abstract = {AIMS: Despite the established link between malignant pleural mesothelioma (MPM) and asbestos exposure, genetic risk factors may play a key role in MPM pathogenesis. The rs9939609 polymorphism in the FTO gene has recently been implicated as a risk factor for some types of cancer, such as breast, pancreatic, and prostate cancers. FTO variation is associated with altered adipocytokine expression and oxidative stress inflammation, which may influence asbestos mediated-carcinogenesis. This is the first study to investigate a possible association between this polymorphism and MPM risk.

MATERIALS AND METHODS: FTO rs9939609 (T >A) genotypes were screened using a TaqMan[®] Genotyping Assay in a total of 235 Egyptian subjects (86 MPM patients versus 149 controls). The chi-square test and logistic regression were used to evaluate the association between the candidate variant and MPM risk using a case-control design.

RESULTS: In the additive genetic model, the AT and AA genotypes were associated with a 2.48-fold (95% confidence intervals [CI] = 1.04-5.92, p = 0.04) and a 3.46-fold (95% CI = 0.99-12.01, p = 0.051) increase in the odds of developing MPM, respectively, when compared to the TT genotype after adjustment for body mass index, age, and gender. Additionally, in the dominant genetic model AT/AA genotypes were associated with a 2.63-fold increase in the odds of developing MPM (95% CI = 1.13-6.12, p = 0.025).

CONCLUSIONS: The present study shows for the first time that rs9939609 polymorphism in the FTO gene may be a genetic risk factor for MPM. This study highlights the association of this genetic polymorphism with cancer susceptibility, and therefore, it should be investigated in various other populations, in relation to different types of cancer, and with larger sample sizes.}, } @article {pmid29260624, year = {2018}, author = {Brosseau, S and Dhalluin, X and Zalcman, G and Scherpereel, A}, title = {Immunotherapy in relapsed mesothelioma.}, journal = {Immunotherapy}, volume = {10}, number = {2}, pages = {77-80}, doi = {10.2217/imt-2017-0144}, pmid = {29260624}, issn = {1750-7448}, mesh = {Antibodies, Monoclonal/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Asbestos/*adverse effects ; Clinical Trials as Topic ; Costimulatory and Inhibitory T-Cell Receptors/immunology ; Humans ; Immunotherapy/*methods ; Lung Neoplasms/mortality/*therapy ; Mesothelioma/mortality/*therapy ; Mesothelioma, Malignant ; Occupational Diseases/immunology/*therapy ; Pleural Neoplasms/immunology/mortality/*therapy ; Recurrence ; Survival Analysis ; Vascular Endothelial Growth Factor A/immunology ; }, } @article {pmid29253374, year = {2017}, author = {Korda, RJ and Clements, MS and Armstrong, BK and Law, HD and Guiver, T and Anderson, PR and Trevenar, SM and Kirk, MD}, title = {Risk of cancer associated with residential exposure to asbestos insulation: a whole-population cohort study.}, journal = {The Lancet. Public health}, volume = {2}, number = {11}, pages = {e522-e528}, doi = {10.1016/S2468-2667(17)30192-5}, pmid = {29253374}, issn = {2468-2667}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Australia/epidemiology ; Cohort Studies ; Environmental Exposure/*adverse effects ; Female ; Housing/*statistics & numerical data ; Humans ; Male ; Middle Aged ; Neoplasms/*chemically induced/epidemiology ; Risk ; }, abstract = {BACKGROUND: The health risks associated with living in houses insulated with asbestos are unknown. Loose-fill asbestos was used to insulate some houses in the Australian Capital Territory (ACT). We compared the incidence of mesothelioma and other cancers in residents of the ACT who did and did not live in these houses.

METHODS: Our cohort study included all ACT residents identified using Medicare enrolment data. These data were linked to addresses of affected residential properties in the ACT to ascertain exposure. We followed up residents by linking data to the Australian Cancer Database and National Death Index. Outcomes were diagnosis of mesothelioma and selected other cancers. Effects were estimated for males and females separately using standardised incidence ratios (SIRs), adjusting for age and calendar time of diagnosis.

FINDINGS: Between Nov 1, 1983, and Dec 31, 2013, 1 035 578 ACT residents were identified from the Medicare database. Of these, 17 248 (2%) had lived in an affected property, including seven (2%) of 285 people diagnosed with mesothelioma. The adjusted incidence of mesothelioma in males who had lived at an affected property was 2·5 times that of unexposed males (SIR 2·54, 95% CI 1·02-5·24). No mesotheliomas were reported among females who had lived at an affected property. Among individuals who had lived at an affected property, there was an elevated incidence of colorectal cancer in women (SIR 1·73, 95% CI 1·29-2·26) and prostate cancer in men (1·29, 1·07-1·54); colorectal cancer was increased, although not significantly, in males (SIR 1·32, 95% CI 0·99-1·72), with no significant increase in the other cancers studied.

INTERPRETATION: Residential asbestos insulation is likely to be unsafe. Our findings have important health, social, financial, and legal implications for governments and communities in which asbestos has been used to insulate houses.

FUNDING: ACT Government.}, } @article {pmid29253372, year = {2017}, author = {de Klerk, N and Reid, A}, title = {Hazards of residential exposure to household asbestos.}, journal = {The Lancet. Public health}, volume = {2}, number = {11}, pages = {e490-e491}, doi = {10.1016/S2468-2667(17)30200-1}, pmid = {29253372}, issn = {2468-2667}, mesh = {*Asbestos ; Housing ; Humans ; *Mesothelioma ; }, } @article {pmid29248759, year = {2018}, author = {Croce, A and Capella, S and Belluso, E and Grosso, F and Mariani, N and Libener, R and Rinaudo, C}, title = {Asbestos fibre burden in gallbladder: A case study.}, journal = {Micron (Oxford, England : 1993)}, volume = {105}, number = {}, pages = {98-104}, doi = {10.1016/j.micron.2017.12.001}, pmid = {29248759}, issn = {1878-4291}, mesh = {Aged, 80 and over ; Asbestos, Crocidolite/isolation & purification/*toxicity ; Asbestos, Serpentine/isolation & purification/*toxicity ; Female ; Gallbladder/*chemistry/pathology ; Humans ; Lung Neoplasms/*mortality/pathology ; Mesothelioma/*mortality/pathology ; Mesothelioma, Malignant ; Occupational Exposure/*adverse effects ; }, abstract = {The methods conventionally used to determine the burden of asbestos fibres inhaled/incorporated in lung require chemical digestion of the biological matrix before counting/characterising the inorganic fibrous phases under scanning electron microscopy and energy dispersive spectroscopy (SEM/EDS). Asbestos fibres can also be present in extra-pulmonary organs, and we set out to quantify the fibres in gallbladder. Although the standardised procedure requires approximately 5 × 10[-1] g of wet tissue, this amount of tissue is not always available. We applied the procedure on about 9 × 10[-4] g of gallbladder from a patient with known environmental and workplace exposure to asbestos. The patient died of malignant pleural mesothelioma and was also affected by severe bile-tract problems. The traditional procedure of digesting tissue samples in NaClO and filtering the resulting suspension was carried out. The filter was then examined under SEM/EDS using two methods 1. following the standardised procedure to assess the fibre burden in lung by investigating only 2 mm[2] of the filter (660 microscopic fields), and 2. analysing all the microscopic fields in one-quarter of the filter (about 82 mm[2]). In parallel, histological sections (prepared in the usual way for medical diagnosis) were analysed without digestion or manipulation of the sample using variable pressure SEM/EDS. The fibre counts obtained using the two methods were of the same order of magnitude, i.e., ∼10[5] fibres/g of wet tissue. We showed that the counting of fibres in human tissue may be successfully carried out even when a limited amount of tissue is available. We also found that, when exposure to asbestos is considerable, the number of asbestos fibres accumulating in the gallbladder may be significant.}, } @article {pmid29247244, year = {2017}, author = {Cerruti, F and Jocollè, G and Salio, C and Oliva, L and Paglietti, L and Alessandria, B and Mioletti, S and Donati, G and Numico, G and Cenci, S and Cascio, P}, title = {Proteasome stress sensitizes malignant pleural mesothelioma cells to bortezomib-induced apoptosis.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {17626}, pmid = {29247244}, issn = {2045-2322}, mesh = {Antineoplastic Agents/*pharmacology ; Apoptosis/*drug effects ; Bortezomib/*pharmacology ; Cell Line, Tumor ; Epithelium/pathology ; Humans ; Lung Neoplasms/*drug therapy ; Mesothelioma/*drug therapy ; Mesothelioma, Malignant ; Proteasome Endopeptidase Complex/*metabolism ; Proteasome Inhibitors/*pharmacology ; Ubiquitinated Proteins/metabolism ; }, abstract = {Based on promising results in preclinical models, clinical trials have been performed to evaluate the efficacy of the first-in-class proteasome inhibitor bortezomib towards malignant pleural mesothelioma (MPM), an aggressive cancer arising from the mesothelium of the serous cavities following exposure to asbestos. Unexpectedly, only minimal therapeutic benefits were observed, thus implicating that MPM harbors inherent resistance mechanisms. Identifying the molecular bases of this primary resistance is crucial to develop novel pharmacologic strategies aimed at increasing the vulnerability of MPM to bortezomib. Therefore, we assessed a panel of four human MPM lines with different sensitivity to bortezomib, for functional proteasome activity and levels of free and polymerized ubiquitin. We found that highly sensitive MPM lines display lower proteasome activity than more bortezomib-resistant clones, suggesting that reduced proteasomal capacity might contribute to the intrinsic susceptibility of mesothelioma cells to proteasome inhibitors-induced apoptosis. Moreover, MPM equipped with fewer active proteasomes accumulated polyubiquitinated proteins, at the expense of free ubiquitin, a condition known as proteasome stress, which lowers the cellular apoptotic threshold and sensitizes mesothelioma cells to bortezomib-induced toxicity as shown herein. Taken together, our data suggest that an unfavorable load-versus-capacity balance represents a critical determinant of primary apoptotic sensitivity to bortezomib in MPM.}, } @article {pmid29244982, year = {2017}, author = {Qin, KR and Dua, D}, title = {Diagnostic Dilemma: Primary Peritoneal Mesothelioma With Para-Occupational Asbestos Exposure.}, journal = {Journal of global oncology}, volume = {3}, number = {6}, pages = {828-832}, pmid = {29244982}, issn = {2378-9506}, mesh = {Antineoplastic Agents/therapeutic use ; *Asbestos ; Carboplatin/therapeutic use ; *Environmental Exposure ; Female ; Humans ; Lung Neoplasms/*diagnosis/drug therapy/pathology ; Mesothelioma/*diagnosis/drug therapy/pathology ; Mesothelioma, Malignant ; Middle Aged ; Pemetrexed/therapeutic use ; Peritoneal Neoplasms/*diagnosis/drug therapy/pathology ; Tomography, X-Ray Computed ; }, } @article {pmid29240325, year = {2017}, author = {}, title = {Tort Law--Expert Testimony in Asbestos Litigation--District of South Carolina Holds the Every Exposure Theory Insufficient to Demonstrate Specific Causation Even If Legal Conclusions are Scientifically Sound.--Haskins v. 3m Co., Nos. 2:15-cv-02086, 3:15-cv-02123, 2017 WL 3118017 (D.S.C. July 21, 2017).}, journal = {Harvard law review}, volume = {131}, number = {2}, pages = {658-665}, pmid = {29240325}, issn = {0017-811X}, mesh = {Asbestosis/*etiology ; *Causality ; Expert Testimony/*legislation & jurisprudence ; Humans ; Mesothelioma/*etiology ; Science ; South Carolina ; }, } @article {pmid29229551, year = {2018}, author = {Nuvoli, B and Camera, E and Mastrofrancesco, A and Briganti, S and Galati, R}, title = {Modulation of reactive oxygen species via ERK and STAT3 dependent signalling are involved in the response of mesothelioma cells to exemestane.}, journal = {Free radical biology & medicine}, volume = {115}, number = {}, pages = {266-277}, doi = {10.1016/j.freeradbiomed.2017.12.008}, pmid = {29229551}, issn = {1873-4596}, mesh = {Acetylcysteine/pharmacology ; Androstadienes/*pharmacology ; Antineoplastic Agents/*pharmacology ; Aromatase Inhibitors/*pharmacology ; Asbestos/adverse effects ; Cell Death ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cyclic AMP/metabolism ; Environmental Exposure/adverse effects ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Humans ; Mesothelioma/*drug therapy ; Oxidative Stress ; Pleural Neoplasms/*drug therapy ; Reactive Oxygen Species/metabolism ; Receptors, Estrogen ; Receptors, G-Protein-Coupled ; STAT3 Transcription Factor/metabolism ; Signal Transduction ; Treatment Outcome ; }, abstract = {Pleural mesothelioma is a deadly form of cancer. The prognosis is extremely poor due to the limited treatment modalities. Uptake of asbestos fibres, the leading cause of mesothelioma, lead to the accumulation of reactive-oxygen-species (ROS). Interestingly, increasing ROS production by using ROS-generating drugs may offer a strategy to selectively trigger cell death. Exemestane, an aromatase inhibitor, has previously shown anti-tumor properties in mesothelioma preclinical models suggesting a role of G protein-coupled receptor 30 (GPR30) in the drug response. As exemestane, in addition to blocking estrogen biosynthesis, generates ROS that are able to arrest the growth of breast cancer, we explored the role of ROS, antioxidant defense system, and ROS-induced signalling pathways in mesothelioma cells during exemestane response. Here we report that exemestane treatment reduced cell proliferation with an increase in ROS production and reduction of cyclic adenosine monophosphate (cAMP) levels in MSTO-H211, Ist-Mes1, Ist-Mes2 and MPP89 exemestane-sensitive mesothelioma cell lines, but not in NCI-H2452 exemestane-insensitive mesothelioma cells. Exemestane induced a significant antioxidant response in NCI-H2452 cells, as highlighted by an increase in γ-glutamylcysteine levels, catalase (Cat), superoxide-dismutase and (SOD) and glutathione-peroxidase (GSH-Px) activity and nuclear factor E2-related factor 2 (Nrf2) activation, responsible for drug insensitivity. Conversely, exemestane elevated ROS levels along with increased ERK phosphorylation and a reduction of p-STA3 in exemestane-sensitive mesothelioma cells. ROS generation was the crucial event of exemestane action because ROS inhibitor N-acetyl-L-cysteine (NAC) abrogated p-ERK and p-STAT3 modulation and cellular death. Exemestane also modulates ERK and STAT3 signalling via GPR30. Results indicate an essential role of ROS in the antiproliferative action of exemestane in mesothelioma cells. It is likely that the additional oxidative insults induced by exemestane results in the lethal effects of mesothelioma cells by increasing ROS production. As such, manipulating ROS levels with exemestane seems to be a feasible strategy to selectively kill mesothelioma cells with less toxicity to normal cells by regulating ERK and STAT3 activity.}, } @article {pmid29209316, year = {2017}, author = {Agostinis, C and Vidergar, R and Belmonte, B and Mangogna, A and Amadio, L and Geri, P and Borelli, V and Zanconati, F and Tedesco, F and Confalonieri, M and Tripodo, C and Kishore, U and Bulla, R}, title = {Complement Protein C1q Binds to Hyaluronic Acid in the Malignant Pleural Mesothelioma Microenvironment and Promotes Tumor Growth.}, journal = {Frontiers in immunology}, volume = {8}, number = {}, pages = {1559}, pmid = {29209316}, issn = {1664-3224}, abstract = {C1q is the first recognition subcomponent of the complement classical pathway, which acts toward the clearance of pathogens and apoptotic cells. C1q is also known to modulate a range of functions of immune and non-immune cells, and has been shown to be involved in placental development and sensorial synaptic pruning. We have recently shown that C1q can promote tumor by encouraging their adhesion, migration, and proliferation in addition to angiogenesis and metastasis. In this study, we have examined the role of human C1q in the microenvironment of malignant pleural mesothelioma (MPM), a rare form of cancer commonly associated with exposure to asbestos. We found that C1q was highly expressed in all MPM histotypes, particularly in epithelioid rather than in sarcomatoid histotype. C1q avidly bound high and low molecular weight hyaluronic acid (HA) via its globular domain. C1q bound to HA was able to induce adhesion and proliferation of mesothelioma cells (MES) via enhancement of ERK1/2, SAPK/JNK, and p38 phosphorylation; however, it did not activate the complement cascade. Consistent with the modular organization of the globular domain, we demonstrated that C1q may bind to HA through ghA module, whereas it may interact with human MES through the ghC. In conclusion, C1q highly expressed in MPM binds to HA and enhances the tumor growth promoting cell adhesion and proliferation. These data can help develop novel diagnostic markers and molecular targets for MPM.}, } @article {pmid29207669, year = {2017}, author = {Lamote, K and Brinkman, P and Vandermeersch, L and Vynck, M and Sterk, PJ and Van Langenhove, H and Thas, O and Van Cleemput, J and Nackaerts, K and van Meerbeeck, JP}, title = {Breath analysis by gas chromatography-mass spectrometry and electronic nose to screen for pleural mesothelioma: a cross-sectional case-control study.}, journal = {Oncotarget}, volume = {8}, number = {53}, pages = {91593-91602}, pmid = {29207669}, issn = {1949-2553}, abstract = {RATIONALE: Malignant pleural mesothelioma (MPM) is mainly caused by previous exposure to asbestos fibers and has a poor prognosis. Due to a long latency period between exposure and diagnosis, MPM incidence is expected to peak between 2020-2025. Screening of asbestos-exposed individuals is believed to improve early detection and hence, MPM management. Recent developments focus on breath analysis for screening since breath contains volatile organic compounds (VOCs) which reflect the cell's metabolism.

OBJECTIVES: The goal of this cross-sectional, case-control study is to identify VOCs in exhaled breath of MPM patients with gas chromatography-mass spectrometry (GC-MS) and to assess breath analysis to screen for MPM using an electronic nose (eNose).

METHODS: Breath and background samples were taken from 64 subjects: 16 healthy controls (HC), 19 asymptomatic former asbestos-exposed (AEx) individuals, 15 patients with benign asbestos-related diseases (ARD) and 14 MPM patients. Samples were analyzed with both GC-MS and eNose.

RESULTS: Using GC-MS, AEx individuals were discriminated from MPM patients with 97% accuracy, with diethyl ether, limonene, nonanal, methylcyclopentane and cyclohexane as important VOCs. This was validated by eNose analysis. MPM patients were discriminated from AEx+ARD participants by GC-MS and eNose with 94% and 74% accuracy, respectively. The sensitivity, specificity, positive and negative predictive values were 100%, 91%, 82%, 100% for GC-MS and 82%, 55%, 82%, 55% for eNose, respectively.

CONCLUSION: This study shows accurate discrimination of patients with MPM from asymptomatic asbestos-exposed persons at risk by GC-MS and eNose analysis of exhaled VOCs and provides proof-of-principle of breath analysis for MPM screening.}, } @article {pmid29206890, year = {2018}, author = {Boffetta, P and Righi, L and Ciocan, C and Pelucchi, C and La Vecchia, C and Romano, C and Papotti, M and Pira, E}, title = {Validation of the diagnosis of mesothelioma and BAP1 protein expression in a cohort of asbestos textile workers from Northern Italy.}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {29}, number = {2}, pages = {484-489}, doi = {10.1093/annonc/mdx762}, pmid = {29206890}, issn = {1569-8041}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Biomarkers, Tumor/analysis ; Cohort Studies ; Female ; Humans ; Italy/epidemiology ; Lung Neoplasms/*epidemiology/etiology ; Male ; Mesothelioma/*epidemiology/etiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/adverse effects ; Peritoneal Neoplasms/*epidemiology/etiology ; Pleural Neoplasms/*epidemiology/etiology ; Textile Industry ; Tumor Suppressor Proteins/*biosynthesis ; Ubiquitin Thiolesterase/*biosynthesis ; }, abstract = {BACKGROUND: Diagnosis of mesothelioma based on death certificate is subject to misclassification, which may bias the results of epidemiology studies. A high proportion of mesothelioma harbor mutations in the BRCA1-associated protein 1 (BAP1) gene.

METHODS: We searched medical and pathology records and specimens for 127 workers from a textile-asbestos factory in Italy who died during 1963-2013 with a diagnosis of pleural or peritoneal neoplasm or mesothelioma on death certificate, to confirm the diagnosis with immunohistochemistry markers. We calculated the odds ratio of confirmation by selected characteristics and asbestos exposure variables. When sufficient pathology material was available, we analyzed BAP1 protein expression.

RESULTS: The diagnosis of mesothelioma was histologically confirmed for 35 cases (27.6%); 5 cases were classified as non-mesothelioma (3.9%), for 33 cases a mention of mesothelioma was found on record but no sufficient material was available for revision (26.0%); no records were available for 54 cases (death-certificate-only 42.5%). Diagnostic confirmation was not associated with sex, location of the neoplasm, age, or duration of employment; however, there was a significant association with time since first employment (P for linear trend 0.04). An association between duration of employment and time since first employment was observed for confirmed cases but not for death-certificate-only cases. BAP1 protein was lost in 18/35 cases (51.4%), without an association with sex, location, age, indices of asbestos exposure, or survival.

CONCLUSIONS: We were able to confirm by immunohistochemistry a small proportion of mesothelioma diagnoses on certificates of deceased asbestos workers, and confirmation correlated with latency of asbestos exposure but not other characteristics. BAP1 protein loss is a frequent event in mesothelioma of asbestos-exposed workers, but does not correlate with exposure.}, } @article {pmid29200597, year = {2017}, author = {Jiang, Z and Ying, S and Shen, W and He, X and Chen, J and Xia, H and Yu, M and Xiao, Y and Feng, L and Zhu, L and Ju, L and Guo, X and Zhang, Y and Shen, JW and Tong, Y and Zhang, X and Lou, J}, title = {Plasma Fibulin-3 as a Potential Biomarker for Patients with Asbestos-Related Diseases in the Han Population.}, journal = {Disease markers}, volume = {2017}, number = {}, pages = {1725354}, pmid = {29200597}, issn = {1875-8630}, mesh = {Aged ; Asbestos/adverse effects ; Asbestosis/*blood/epidemiology ; Biomarkers/blood ; Case-Control Studies ; China ; Extracellular Matrix Proteins/*blood ; Female ; Humans ; Lung Neoplasms/*blood/epidemiology ; Male ; Mesothelioma/*blood/epidemiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/statistics & numerical data ; }, abstract = {Fibulin-3 has been reported as a potential biomarker for mesothelioma. However, little is known about the diagnostic efficacies of fibulin-3 for asbestos-related diseases (ARDs) in China. This study was to investigate the utility of fibulin-3 for asbestos exposure and ARDs. A total of 430 subjects were recruited from Southeast China, including healthy individuals, asbestos-exposed (AE) individuals, and patients with pleural plaques (PP), asbestosis, and malignant pleural mesothelioma (MPM). Plasma fibulin-3 was measured using the enzyme-linked immunosorbent assay. Linear regression analyses were applied to explore the influencing factors of fibulin-3. Receiver operating characteristic curves were used to determine the cutoff values. The median fibulin-3 level of subjects in the mesothelioma group was higher than that in other groups. Subjects in the asbestosis group had higher median fibulin-3 level than those in the control group. A higher fibulin-3 level was found in the group with ≥10 years of asbestos exposure as compared with control groups. The AUCs of fibulin-3 for distinguishing MPM subjects from control, AE, PP, and asbestosis subjects were 0.92, 0.88, 0.90, and 0.81, respectively. Our study provided evidence that fibulin-3 could be a potential biomarker for the early screening of MPM, but not of other nonmalignant ARDs in Chinese populations.}, } @article {pmid29197906, year = {2017}, author = {Glass, WI and Clayson, H}, title = {Asbestos-worker exposure, family disease.}, journal = {The New Zealand medical journal}, volume = {130}, number = {1466}, pages = {90-91}, pmid = {29197906}, issn = {1175-8716}, mesh = {Asbestos/*toxicity ; *Family Health/economics/legislation & jurisprudence ; Humans ; *Inhalation Exposure ; Lung Neoplasms/chemically induced/economics ; Mesothelioma/chemically induced/economics ; *Occupational Exposure ; *Workers' Compensation/economics/legislation & jurisprudence ; }, abstract = {Family members, mostly female, can be at risk of asbestos-related disease as a result of the transfer of asbestos from the workplace to the home on the hair, boots and clothes of the worker. It is argued that in these cases the home should be recognised as an extension of the workplace and that the employer has a duty of care to contain and control the asbestos. Given these circumstances, the family member with the disease should be entitled to cover under the Accidence Compensation Legislation.}, } @article {pmid29197848, year = {2017}, author = {Gravito-Soares, M and Gravito-Soares, E and Almeida, J and Fraga, J and Tomé, L}, title = {Challenging and uncommon diagnosis of long-evolution ascites.}, journal = {BMJ case reports}, volume = {2017}, number = {}, pages = {}, pmid = {29197848}, issn = {1757-790X}, mesh = {Alcoholism/*complications ; Ascites/*complications/pathology ; Biopsy ; Humans ; Liver/pathology ; Male ; Mesothelioma/*etiology/pathology ; Middle Aged ; Peritoneal Neoplasms/*etiology/pathology ; Peritoneum/pathology ; }, abstract = {This is a case report of a 45-year-old Caucasian man with chronic alcoholism. No history of liver disease or asbestos exposure. He complained of ascites during the last 3 years with worsening in the last year with severe ascites development. Diagnostic paracentesis showed SAAG 1.1 and high cellularity with neutrophil count >250 cells/µL. Ascitic fluid cytology revealed reactive mesothelial hyperplasia. Thoracoabdominopelvic ultrasonography/CT/MRI and fludeoxyglucose positron emission tomography/CT showed 'omental cake' pattern suggesting peritoneal carcinomatosis. An exploratory laparoscopy revealed moderate interloop adhesions and necrosis with whitish exudate in the right pelvic excavation. Biochemical/cytological/histological/microbiological study only revealed reactive mesothelial cells, necrosis and lymphohistiocytic inflammatory infiltrate. A second exploratory laparoscopy with liver and peritoneal biopsies and appendectomy/mesoappendix excision showed a well-differentiated tubulopapillary mesothelioma. The patient was referred for intraperitoneal chemotherapy and is undergoing monthly therapeutic paracentesis.}, } @article {pmid29193587, year = {2018}, author = {Ohara, Y and Chew, SH and Shibata, T and Okazaki, Y and Yamashita, K and Toyokuni, S}, title = {Phlebotomy as a preventive measure for crocidolite-induced mesothelioma in male rats.}, journal = {Cancer science}, volume = {109}, number = {2}, pages = {330-339}, pmid = {29193587}, issn = {1349-7006}, mesh = {Animals ; Asbestos, Crocidolite/*toxicity ; Disease Models, Animal ; Iron/blood ; Lung Neoplasms/blood/*chemically induced/pathology/*prevention & control ; Male ; Mesothelioma/blood/*chemically induced/pathology/*prevention & control ; Mesothelioma, Malignant ; Phlebotomy/*methods ; Rats ; Survival Analysis ; Treatment Outcome ; Tumor Burden ; }, abstract = {Malignant mesothelioma (MM) is a rare but socially important neoplasm due to its association with asbestos exposure. Malignant mesothelioma is difficult to diagnose at an early stage, yet there are no particularly effective treatments available at the advanced stage, thus necessitating efficient strategies to prevent MM in individuals already exposed to asbestos. We previously showed that persistent oxidative damage caused by foreign body reaction and affinity of asbestos both to hemoglobin and histones is one of the major pathogeneses. Accordingly, as an effective strategy to prevent asbestos-induced MM, we undertook the use of an iron chelator, deferasirox, which decreased the epithelial-mesenchymal transition in a crocidolite-induced rat MM model. However, this agent may show adverse effects. Here, we studied the effects of iron removal by phlebotomy as a realistic measure on the same rat model. We injected a total of 5 mg crocidolite i.p. to F1 hybrid rats between the Fischer-344 and Brown-Norway strains at the age of 6 weeks. We repeated weekly or biweekly phlebotomy of 6-8 mL/kg/time from 10 to 60 weeks of age. The animals were observed until 120 weeks. In male rats, phlebotomy significantly decreased the weight and nuclear grade of MM, and modestly reduced the associated ascites and the fraction of more malignant sarcomatoid subtype. Weekly phlebotomy prolonged long-term survival. Our results indicate that appropriate phlebotomy may be a practical preventive measure to attenuate the initiation and promotion capacity of asbestos towards MM by reducing iron in individuals exposed to asbestos.}, } @article {pmid29187476, year = {2017}, author = {Matsubara, T and Toyokawa, G and Yamada, Y and Nabeshima, K and Haratake, N and Kozuma, Y and Akamine, T and Takamori, S and Shoji, F and Okamoto, T and Maehara, Y}, title = {A Case of the Resected Lymphohistiocytoid Mesothelioma: BAP1 Is a Key of Accurate Diagnosis.}, journal = {Anticancer research}, volume = {37}, number = {12}, pages = {6937-6941}, doi = {10.21873/anticanres.12158}, pmid = {29187476}, issn = {1791-7530}, mesh = {Aged, 80 and over ; Biomarkers, Tumor/analysis ; Diagnosis, Differential ; Fluorodeoxyglucose F18 ; Humans ; Immunohistochemistry ; Lung Neoplasms/diagnosis/diagnostic imaging/*surgery ; Male ; Mesothelioma/diagnosis/diagnostic imaging/*surgery ; Mesothelioma, Malignant ; Positron-Emission Tomography/methods ; Tomography, X-Ray Computed/methods ; Tumor Suppressor Proteins/analysis ; Ubiquitin Thiolesterase/analysis ; }, abstract = {BACKGROUND: Malignant mesothelioma (MM) is a well-known malignant tumor that occurs in the pleura and is histopathologically classified into three subtypes. Lymphohistiocytoid mesothelioma (LHM) is considered a variant of epithelioid MM, and few cases have been reported. First case of LHM was reported by Henderson et al. in 1988. It is difficult to precisely diagnose LHM, and it is often misdiagnosed as reactive mesothelial cell proliferation.

CASE REPORT: An 82-year-old man, with the smoking history of nine pack-years, was referred to our Department due to an abnormal shadow and pleural effusion in the left lung field on the chest X-ray imaging. His occupation was a teacher through his life without any asbestos exposure. Computed tomography (CT) and [18]F-fluorodeoxyglucose-position emission tomography showed a tumor which was suggestive of malignancy on the left chest wall, with the possible invasion into the left 2nd to 4th ribs. He underwent a CT-guided biopsy and a thoracentesis, but the tumor was shown to be a benign tumor indicative of a reactive mesothelial cell proliferation. Then, he underwent a surgical resection and the tumor was suspected of liposarcoma macroscopically. Histological and immunohistochemical findings were suggestive of mesothelial lesion, such as nodular histiocytic or mesothelial hyperplasia. However, loss of BAP1 and no p16 homozygous deletion in the tumor cells led to the diagnosis of LHM, not a benign lesion.}, } @article {pmid29182465, year = {2017}, author = {}, title = {Author's response to: "Letter to the Editor" regarding content of "Mesothelioma from asbestos exposures: Epidemiologic patterns and impact in the United States" by R. A. Lemen, Journal of Toxicology and Environmental Health, Part B 2016; 19: 250-265.}, journal = {Journal of toxicology and environmental health. Part B, Critical reviews}, volume = {20}, number = {8}, pages = {389}, doi = {10.1080/10937404.2017.1400769}, pmid = {29182465}, issn = {1521-6950}, mesh = {Asbestos/*analysis ; Environmental Health ; Lung Neoplasms ; *Mesothelioma ; Pleural Neoplasms ; United States ; }, } @article {pmid29165392, year = {2017}, author = {Westerholm, P and Remaéus, B and Svartengren, M}, title = {The Tale of Asbestos in Sweden 1972-1986-The Pathway to a Near-Total Ban.}, journal = {International journal of environmental research and public health}, volume = {14}, number = {11}, pages = {}, pmid = {29165392}, issn = {1660-4601}, mesh = {Asbestos/*adverse effects ; Asbestos, Serpentine/adverse effects ; Asbestosis/*epidemiology ; Environmental Exposure/*statistics & numerical data ; Humans ; Incidence ; Lung Neoplasms/chemically induced ; Mesothelioma/chemically induced ; Mesothelioma, Malignant ; Occupational Exposure/statistics & numerical data ; Sweden ; }, abstract = {This paper provides a narrative of the national intervention strategy in Sweden aimed to restrict the industrial use of asbestos. For many years, asbestos was imported for widespread industrial use, resulting in large amounts throughout Swedish society. In 1972, the whistle was blown in a Communist Party parliamentary motion describing asbestos as a health hazard and requesting action to prohibit its use. Although the motion was rejected, it initiated the extensive charting of asbestos sources on a tripartite basis, involving government agencies, and employer and trade-union organizations. Restrictive asbestos management practices were enforced from July 1982. The year 1985 saw the Government Asbestos Commission review, covering use-determining factors, international regulations, and assessments of cancer risks. The relative risks of chrysotile and amphibole were considered internationally (by the IARC), since chrysotile (a Canadian export) was regarded as unharmful in Canada at that time. Prohibiting asbestos use resulted in its virtual disappearance as an import to Sweden from the early 1980s. However, asbestos has undergone a transition from an occupational to a public-health hazard (although some work-related hazards, such as handling and disposal, remain). The transition reflects the public's exposure to existing stocks, in homes, workplaces, etc. Mesothelioma incidence has come to be regarded as an indicator of prevention effectiveness.}, } @article {pmid29165150, year = {2017}, author = {Matsuzaki, H and Kumagai-Takei, N and Lee, S and Maeda, M and Sada, N and Hatayama, T and Yamamoto, S and Ikeda, M and Yoshitome, K and Min, Y and Nishimura, Y and Otsuki, T}, title = {Search for biomarkers of asbestos exposure and asbestos-induced cancers in investigations of the immunological effects of asbestos.}, journal = {Environmental health and preventive medicine}, volume = {22}, number = {1}, pages = {53}, pmid = {29165150}, issn = {1347-4715}, mesh = {Asbestos/*adverse effects/*immunology ; Asbestosis/immunology ; Biomarkers/*analysis/blood ; CD8-Positive T-Lymphocytes ; Humans ; Killer Cells, Natural/*immunology ; Lung Neoplasms/chemically induced/immunology ; Mesothelioma/chemically induced/immunology ; Mesothelioma, Malignant ; Mucosal-Associated Invariant T Cells/*immunology ; T-Lymphocytes, Helper-Inducer ; T-Lymphocytes, Regulatory ; }, abstract = {The immunological effects of asbestos exposure on various lymphocytes such as the regulatory T cell (Treg), responder CD4+ T helper cell (Tresp), CD8+ cytotoxic T lymphocytes (CTL), and natural killer (NK) cells were investigated. Results show that asbestos exposure impairs antitumor immunity through enhancement of regulatory T cell function and volume, reduction of CXCR3 chemokine receptor in responder CD4+ T helper cells, and impairment of the killing activities of CD8+ cytotoxic T lymphocytes (CTL) and NK cells. These findings were used to explore biological markers associated with asbestos exposure and asbestos-induced cancers and suggested the usefulness of serum/plasma IL-10 and TGF-β, surface CXCR3 expression in Tresp, the secreting potential of IFN-γ in Tresp, intracellular perforin level in CTL, and surface expression NKp46 in NK cells. Although other unexplored cytokines in serum/plasma and molecules in these immunological cells, including Th17, should be investigated by experimental procedures in addition to a comprehensive analysis of screening methods, biomarkers based on immunological alterations may be helpful in clinical situations to screen the high-risk population exposed to asbestos and susceptible to asbestos-related cancers such as mesothelioma.}, } @article {pmid29149911, year = {2017}, author = {Winata, P and Williams, M and McGowan, E and Nassif, N and van Zandwijk, N and Reid, G}, title = {The analysis of novel microRNA mimic sequences in cancer cells reveals lack of specificity in stem-loop RT-qPCR-based microRNA detection.}, journal = {BMC research notes}, volume = {10}, number = {1}, pages = {600}, pmid = {29149911}, issn = {1756-0500}, support = {11/TPG/3-06//Cancer Institute NSW/ ; 11/TPG/3-06//Cancer Institute NSW/ ; PhD Scholarship//Sydney Catalyst/ ; RG14-17//Cancer Council NSW/ ; }, mesh = {Antineoplastic Agents/administration & dosage/*analysis/therapeutic use ; Cell Line, Tumor ; *Drug Delivery Systems ; Humans ; Lung Neoplasms/*drug therapy ; Mesothelioma/*drug therapy ; Mesothelioma, Malignant ; MicroRNAs/administration & dosage/*analysis/chemical synthesis/therapeutic use ; Molecular Mimicry ; *Molecular Probe Techniques ; Nucleic Acid Probes ; *Real-Time Polymerase Chain Reaction ; Reverse Transcription ; Sensitivity and Specificity ; }, abstract = {OBJECTIVE: MicroRNAs are frequently downregulated in cancer, and restoring expression has tumour suppressive activity in tumour cells. Our recent phase I clinical trial investigated microRNA-based therapy in patients with malignant pleural mesothelioma. Treatment with TargomiRs, microRNA mimics with novel sequence packaged in EGFR antibody-targeted bacterial minicells, revealed clear signs of clinical activity. In order to detect delivery of microRNA mimics to tumour cells in future clinical trials, we tested hydrolysis probe-based assays specific for the sequence of the novel mimics in transfected mesothelioma cell lines using RT-qPCR.

RESULTS: The custom assays efficiently and specifically amplified the consensus mimics. However, we found that these assays gave a signal when total RNA from untransfected and control mimic-transfected cells were used as templates. Further investigation revealed that the reverse transcription step using stem-loop primers appeared to introduce substantial non-specific amplification with either total RNA or synthetic RNA templates. This suggests that reverse transcription using stem-loop primers suffers from an intrinsic lack of specificity for the detection of highly similar microRNAs in the same family, especially when analysing total RNA. These results suggest that RT-qPCR is unlikely to be an effective means to detect delivery of microRNA mimic-based drugs to tumour cells in patients.}, } @article {pmid29137208, year = {2017}, author = {Marsili, D and Angelini, A and Bruno, C and Corfiati, M and Marinaccio, A and Silvestri, S and Zona, A and Comba, P}, title = {Asbestos Ban in Italy: A Major Milestone, Not the Final Cut.}, journal = {International journal of environmental research and public health}, volume = {14}, number = {11}, pages = {}, pmid = {29137208}, issn = {1660-4601}, mesh = {*Air Pollutants, Occupational ; *Asbestos ; Environmental Health ; *Environmental Policy ; Humans ; Italy ; Occupational Exposure/*prevention & control ; }, abstract = {Background and history: Italy was the main asbestos producer and one of the greatest consumers in 20th century Europe until the asbestos ban was introduced in 1992. Asbestos exposure affected the population in a wide range of working environments, namely mining and marketing of asbestos, asbestos cement production, shipyards and textile industries. This also determined a widespread environmental asbestos exposure affecting the surrounding communities. Methods: To investigate the drivers and difficulties of the process leading to the asbestos ban and its subsequent implementation, we focused on stakeholder involvement, environmental health policies, capacity building and communication. Results: In the past three decades, stakeholder involvement has been instrumental in advancing the industrial asbestos replacement process, prevention and remediation interventions. Furthermore, involvement also contributed to the integration of environmental and health policies at national, regional and local levels, including capacity building and communication. In a global public health perspective, international scientific cooperation has been established with countries using and producing asbestos. Discussion and Conclusions: Key factors and lessons learnt in Italy from both successful and ineffective asbestos policies are described to support the relevant stakeholders in countries still using asbestos contributing to the termination of its use.}, } @article {pmid29131723, year = {2017}, author = {Magnani, C and Mirabelli, D and Terracini, B}, title = {Comment on "Mesothelioma from asbestos exposures: Epidemiologic patterns and impact in the United States" by R A Lemen, Journal of Toxicology and Environmental Health, Part B 2016;19:250-265.}, journal = {Journal of toxicology and environmental health. Part B, Critical reviews}, volume = {20}, number = {8}, pages = {387-388}, doi = {10.1080/10937404.2017.1400762}, pmid = {29131723}, issn = {1521-6950}, mesh = {*Asbestos ; Environmental Health ; Humans ; Lung Neoplasms ; *Mesothelioma ; United States ; }, } @article {pmid29129162, year = {2017}, author = {Musk, ABW and de Klerk, N and Brims, FJ}, title = {Mesothelioma in Australia: a review.}, journal = {The Medical journal of Australia}, volume = {207}, number = {10}, pages = {449-452}, doi = {10.5694/mja17.00397}, pmid = {29129162}, issn = {1326-5377}, mesh = {Antineoplastic Agents/therapeutic use ; *Asbestos ; Australia/epidemiology ; Compensation and Redress ; Humans ; Incidence ; Mesothelioma/drug therapy/*epidemiology ; Occupational Diseases/drug therapy/*epidemiology ; Occupational Exposure/statistics & numerical data ; Pleural Neoplasms/drug therapy/*epidemiology ; Prognosis ; }, abstract = {The incidence of malignant mesothelioma in Australia is among the highest in the world as a result of widespread use of asbestos by industry and in construction throughout the 20th century. The risk of developing malignant mesothelioma after asbestos exposure is dose-related; a transient, low dose exposure confers a correspondingly very low risk of disease. Malignant mesothelioma is a heterogeneous disease, partly explaining the limited role of biomarkers in screening and diagnosis. The prognosis remains poor, and early advice on medico-legal compensation and a collaborative team approach to managing malignant mesothelioma are both essential. Chemotherapy can have a modest treatment effect in some people. New therapies, such as immunotherapy, do not yet have a defined role in the treatment of malignant mesothelioma. As treatment options for malignant mesothelioma are limited and no cure is available, there is no established role for early detection or screening of at risk populations. A multidisciplinary approach to caring for patients with malignant mesothelioma and their carers is vital.}, } @article {pmid29124998, year = {2017}, author = {Pierce, JS and Riordan, AS and Miller, EW and Gaffney, SH and Hollins, DM}, title = {Evaluation of the presence of asbestos in cosmetic talcum products.}, journal = {Inhalation toxicology}, volume = {29}, number = {10}, pages = {443-456}, doi = {10.1080/08958378.2017.1392656}, pmid = {29124998}, issn = {1091-7691}, mesh = {Asbestos, Amphibole/*analysis ; Cosmetics/*chemistry ; Humans ; Microscopy, Electron, Transmission ; Spectrometry, X-Ray Emission ; Talc/*chemistry ; X-Ray Diffraction ; }, abstract = {Talc has been used for over a century in a variety of cosmetic products. While pure cosmetic talc (free of asbestos) is not considered a risk factor for mesothelioma, it has been recently suggested that inhalation of cosmetic talc containing trace levels of asbestos is a risk factor for mesothelioma. Bulk analyses of cosmetic talcum products were performed in the 1960s and 1970s, however, the analytical methods used at that time were incapable of determining whether asbestos minerals were present in the asbestiform versus non-asbestiform habit. The distinction between these two mineral habits is critical, as non-asbestiform amphibole minerals do not present an asbestos-related cancer risk via inhalation. As such, we evaluated six historical talcum powders using modern-era analytical methods to determine if asbestos is present, and if so, to identify the mineral habit (asbestiform versus non-asbestiform) of the asbestos. Based on their labels, the products were produced by four manufacturers and sold between 1940 and 1977. The products were analyzed in duplicate by two laboratories using standard protocols. Laboratory A analyzed samples using X-ray diffraction (XRD) and polarized light microscopy (PLM), and Laboratory B analyzed samples using PLM and transmission electron microscopy (TEM) with energy dispersive X-ray analysis (EDX) and selected area electron diffraction (SAED). No asbestiform minerals were found in any of the products. Nonetheless, even if some historical cosmetic talcum products contained trace amounts (≤0.1%) of asbestiform minerals, any resulting asbestos exposure would be expected to be exceedingly low, and comparable to exposures from breathing ambient air.}, } @article {pmid29124996, year = {2017}, author = {LeMasters, G and Lockey, JE and Hilbert, TJ and Levin, LS and Burkle, JW and Shipley, R and Perme, C and Meyer, CA and Rice, CH}, title = {A 30-year mortality and respiratory morbidity study of refractory ceramic fiber workers.}, journal = {Inhalation toxicology}, volume = {29}, number = {10}, pages = {462-470}, doi = {10.1080/08958378.2017.1394931}, pmid = {29124996}, issn = {1091-7691}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Kaolin/*toxicity ; Male ; Middle Aged ; Mineral Fibers/*toxicity ; Neoplasms/etiology ; *Occupational Exposure ; Odds Ratio ; Respiratory Tract Diseases/*etiology/*mortality ; Risk Factors ; Young Adult ; }, abstract = {AIM: Report mortality (n = 1119), cancer incidence (n = 1207) and radiographic (n = 1451) findings from a 30-year investigation of current and former refractory ceramic fiber (RCF) workers.

METHODS: Cause of death, health and work histories, radiographs and spirometry were collected. Mortality and cancer incidence were analyzed. Logistic regression analysis investigated the associations of latency and cumulative fiber exposure (CFE) on radiographic changes.

RESULTS: The mortality study showed no increase in standardized mortality rates (SMR) for lung cancer, but urinary cancers were significantly elevated in the higher exposed group (SMR = 3.62, 95% CI: 1.33-7.88) and leukemia in the total cohort (SMR = 2.51, 95% CI: 1.08-4.94). One death attributed to mesothelioma was identified (SMR = 2.86, 95% CI: 0.07-15.93) in a worker reporting some asbestos exposure. The overall rate of pleural changes was 6.1%, attaining 21.4% in the highest CFE category for all subjects (adjusted odds ratio (aOR) = 6.9, 95% CI: 3.6-13.4), and 13.0% for those with no reported asbestos exposure (OR= 9.1, 95% CI: 2.5-33.6). Prevalence for recent hires (≥1985) was similar to the background. Interstitial changes were not elevated. Localized pleural thickening was associated with small decreases in spirometry results.

CONCLUSION: Increases in leukemia and urinary cancer but not lung cancer mortality were found. One death attributed to mesothelioma was observed in a worker with self-reported asbestos exposure and a work history where occupational asbestos exposure may have occurred, rendering uncertainties in assigning causation. Radiographic analyses indicated RCF exposure alone is associated with increased pleural but not interstitial changes. Reductions in RCF exposure should continue. The mortality study is ongoing.}, } @article {pmid29113949, year = {2018}, author = {Johnson, TG and Schelch, K and Cheng, YY and Williams, M and Sarun, KH and Kirschner, MB and Kao, S and Linton, A and Klebe, S and McCaughan, BC and Lin, RCY and Pirker, C and Berger, W and Lasham, A and van Zandwijk, N and Reid, G}, title = {Dysregulated Expression of the MicroRNA miR-137 and Its Target YBX1 Contribute to the Invasive Characteristics of Malignant Pleural Mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {13}, number = {2}, pages = {258-272}, doi = {10.1016/j.jtho.2017.10.016}, pmid = {29113949}, issn = {1556-1380}, mesh = {Animals ; Cell Movement/physiology ; DNA Methylation ; Gene Knockdown Techniques ; Heterografts ; Humans ; Lung Neoplasms/genetics/*metabolism/pathology ; Mesothelioma/genetics/*metabolism/pathology ; Mesothelioma, Malignant ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; MicroRNAs/antagonists & inhibitors/biosynthesis/genetics/*metabolism ; Neoplasm Invasiveness ; Pleural Neoplasms/genetics/*metabolism/pathology ; Promoter Regions, Genetic ; Transfection ; Y-Box-Binding Protein 1/genetics/*metabolism ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is an aggressive malignancy linked to asbestos exposure. On a genomic level, MPM is characterized by frequent chromosomal deletions of tumor suppressors, including microRNAs. MiR-137 plays a tumor suppressor role in other cancers, so the aim of this study was to characterize it and its target Y-box binding protein 1 (YBX1) in MPM.

METHODS: Expression, methylation, and copy number status of miR-137 and its host gene MIR137HG were assessed by polymerase chain reaction. Luciferase reporter assays confirmed a direct interaction between miR-137 and Y-box binding protein 1 gene (YBX1). Cells were transfected with a miR-137 inhibitor, miR-137 mimic, and/or YBX1 small interfering RNA, and growth, colony formation, migration and invasion assays were conducted.

RESULTS: MiR-137 expression varied among MPM cell lines and tissue specimens, which was associated with copy number variation and promoter hypermethylation. High miR-137 expression was linked to poor patient survival. The miR-137 inhibitor did not affect target levels or growth, but interestingly, it increased miR-137 levels by means of mimic transfection suppressed growth, migration, and invasion, which was linked to direct YBX1 downregulation. YBX1 was overexpressed in MPM cell lines and inversely correlated with miR-137. RNA interference-mediated YBX1 knockdown significantly reduced cell growth, migration, and invasion.

CONCLUSIONS: MiR-137 can exhibit a tumor-suppressive function in MPM by targeting YBX1. YBX1 knockdown significantly reduces tumor growth, migration, and invasion of MPM cells. Therefore, YBX1 represents a potential target for novel MPM treatment strategies.}, } @article {pmid29112873, year = {2017}, author = {Port, J and Murphy, DJ}, title = {Mesothelioma: Identical Routes to Malignancy from Asbestos and Carbon Nanotubes.}, journal = {Current biology : CB}, volume = {27}, number = {21}, pages = {R1173-R1176}, doi = {10.1016/j.cub.2017.07.026}, pmid = {29112873}, issn = {1879-0445}, mesh = {Animals ; *Asbestos ; Humans ; Inflammation ; *Lung Neoplasms ; *Mesothelioma ; Mice ; *Nanotubes, Carbon ; }, abstract = {Exposure of laboratory mice to carbon nanotubes mimics exposure to asbestos, from initial and chronic inflammation, through loss of the same tumour-suppressor pathways and eventual sporadic development of malignant mesothelioma. Fibres of a similar nature may pose significant health risks to humans.}, } @article {pmid29112861, year = {2017}, author = {Chernova, T and Murphy, FA and Galavotti, S and Sun, XM and Powley, IR and Grosso, S and Schinwald, A and Zacarias-Cabeza, J and Dudek, KM and Dinsdale, D and Le Quesne, J and Bennett, J and Nakas, A and Greaves, P and Poland, CA and Donaldson, K and Bushell, M and Willis, AE and MacFarlane, M}, title = {Long-Fiber Carbon Nanotubes Replicate Asbestos-Induced Mesothelioma with Disruption of the Tumor Suppressor Gene Cdkn2a (Ink4a/Arf).}, journal = {Current biology : CB}, volume = {27}, number = {21}, pages = {3302-3314.e6}, pmid = {29112861}, issn = {1879-0445}, support = {MC_U132685863/MRC_/Medical Research Council/United Kingdom ; MC_UP_1203/1/MRC_/Medical Research Council/United Kingdom ; MC_UP_A600_1023/MRC_/Medical Research Council/United Kingdom ; MC_UP_A600_1024/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Aged ; Animals ; Asbestos/*toxicity ; Carcinogenesis/chemically induced/genetics ; Cell Proliferation/drug effects ; Cells, Cultured ; Cyclin-Dependent Kinase Inhibitor p16/genetics/*metabolism ; Cyclin-Dependent Kinase Inhibitor p19/genetics/*metabolism ; Female ; Humans ; Lung Neoplasms/*chemically induced/genetics/*pathology ; Male ; Mesothelioma/*chemically induced/genetics/*pathology ; Mesothelioma, Malignant ; Methylation/drug effects ; Mice ; Mice, Inbred C57BL ; Middle Aged ; Nanotubes, Carbon/*toxicity ; }, abstract = {Mesothelioma is a fatal tumor of the pleura and is strongly associated with asbestos exposure. The molecular mechanisms underlying the long latency period of mesothelioma and driving carcinogenesis are unknown. Moreover, late diagnosis means that mesothelioma research is commonly focused on end-stage disease. Although disruption of the CDKN2A (INK4A/ARF) locus has been reported in end-stage disease, information is lacking on the status of this key tumor suppressor gene in pleural lesions preceding mesothelioma. Manufactured carbon nanotubes (CNTs) are similar to asbestos in terms of their fibrous shape and biopersistent properties and thus may pose an asbestos-like inhalation hazard. Here we show that instillation of either long CNTs or long asbestos fibers into the pleural cavity of mice induces mesothelioma that exhibits common key pro-oncogenic molecular events throughout the latency period of disease progression. Sustained activation of pro-oncogenic signaling pathways, increased proliferation, and oxidative DNA damage form a common molecular signature of long-CNT- and long-asbestos-fiber-induced pathology. We show that hypermethylation of p16/Ink4a and p19/Arf in CNT- and asbestos-induced inflammatory lesions precedes mesothelioma; this results in silencing of Cdkn2a (Ink4a/Arf) and loss of p16 and p19 protein, consistent with epigenetic alterations playing a gatekeeper role in cancer. In end-stage mesothelioma, silencing of p16/Ink4a is sustained and deletion of p19/Arf is detected, recapitulating human disease. This study addresses the long-standing question of which early molecular changes drive carcinogenesis during the long latency period of mesothelioma development and shows that CNT and asbestos pose a similar health hazard.}, } @article {pmid29111984, year = {2018}, author = {Ripabelli, G and Tamburro, M and Di Tella, D and Carrozza, F and Sammarco, ML}, title = {Asbestos Exposures, Mesothelioma Incidence and Mortality, and Awareness by General Practitioners in the Molise Region, Central Italy.}, journal = {Journal of occupational and environmental medicine}, volume = {60}, number = {2}, pages = {e90-e97}, doi = {10.1097/JOM.0000000000001211}, pmid = {29111984}, issn = {1536-5948}, mesh = {Adult ; Age Factors ; Aged ; Asbestosis/diagnosis/epidemiology ; Clinical Competence ; *Environmental Exposure ; Female ; *General Practitioners ; *Health Knowledge, Attitudes, Practice ; Humans ; Incidence ; Italy/epidemiology ; Lung Neoplasms/*epidemiology/mortality ; Male ; Mesothelioma/diagnosis/*epidemiology/mortality ; Middle Aged ; Pleural Neoplasms/*epidemiology/mortality ; Registries ; }, abstract = {OBJECTIVE: The aim of this study was to evaluate environmental asbestos sources, mesothelioma incidence and mortality, and awareness on asbestos-related diseases (ARDs) by general practitioners (GPs) in Molise Region.

METHODS: The contaminated sites in three towns were identified by census; mesothelioma incidence (2000 to 2012) and mortality (2003 to 2013) was achieved from local registries; GPs were interviewed on practiced population's exposures and ARDs diagnosis.

RESULTS: About 54.3% of visited sites were contaminated (71.2% by friable asbestos) and 38.8% was extremely damaged. Over above time-periods, 32 mesothelioma cases (62.5% males, 25% in people aged 70 to 75 years) and 27 deaths (90% males, 69 ± 10 years, 70.4% pleural mesothelioma) have been reported. A total of 122 GPs were interviewed who had diagnosed 40 mesothelioma and 28 asbestosis cases.

CONCLUSION: There is the need of remediation/removal interventions for contaminated sites and of strategies to increase GPs awareness on asbestos risks for better patients' management.}, } @article {pmid29100460, year = {2017}, author = {Birnie, KA and Prêle, CM and Thompson, PJ and Badrian, B and Mutsaers, SE}, title = {Targeting microRNA to improve diagnostic and therapeutic approaches for malignant mesothelioma.}, journal = {Oncotarget}, volume = {8}, number = {44}, pages = {78193-78207}, pmid = {29100460}, issn = {1949-2553}, abstract = {Malignant mesothelioma is an aggressive and often fatal cancer associated with asbestos exposure. The disease originates in the mesothelial lining of the serosal cavities, most commonly affecting the pleura. Survival rates are low as diagnosis often occurs at an advanced stage and current treatments are limited. Identifying new diagnostic and therapeutic targets for mesothelioma remains a priority, particularly for the new wave of victims exposed to asbestos through do-it-yourself renovations and in countries where asbestos is still mined and used. Recent advances have demonstrated a biological role for the small but powerful gene regulators microRNA (miRNA) in mesothelioma. A number of potential therapeutic targets have been identified. MiRNA have also become popular as potential biomarkers for mesothelioma due to their stable expression in bodily fluid and tissues. In this review, we highlight the current challenges associated with the diagnosis and treatment of mesothelioma and discuss how targeting miRNA may improve diagnostic, prognostic and therapeutic approaches.}, } @article {pmid29099505, year = {2018}, author = {Feder, IS and Theile, A and Tannapfel, A}, title = {Histological findings and lung dust analysis as the basis for occupational disease compensation in asbestos-related lung cancer in Germany.}, journal = {International journal of occupational medicine and environmental health}, volume = {31}, number = {3}, pages = {293-305}, doi = {10.13075/ijomeh.1896.01148}, pmid = {29099505}, issn = {1896-494X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*analysis ; Asbestosis/*diagnosis/diagnostic imaging/pathology ; Dust/analysis ; Germany ; Histological Techniques ; Humans ; Lung Diseases/*diagnosis/pathology ; Middle Aged ; Occupational Diseases/*diagnosis/pathology ; Occupational Exposure/statistics & numerical data ; Pleural Diseases/diagnosis/pathology ; Workers' Compensation ; }, abstract = {OBJECTIVES: This study has researched the significance of histologically raised findings and lung dust analyses in the context of claiming the recognition of and thus compensation for an asbestos-associated occupational disease.

MATERIAL AND METHODS: For this approach, all findings from the German Mesothelioma Register in 2015 that included lung dust analyses were evaluated and were compared with information on asbestos fiber exposure at work based on fiber years, and with the results of radiological findings.

RESULTS: For 68 insured persons, recognition of an asbestos-induced lung disease according to Section 4104 of the German Ordinance on Occupational Diseases (Berufskrankheitenverordnung - BKV) could be recommended solely on the basis of the histological examinations of lung tissues and complementary lung dust analyses. Neither did the calculation of the cumulative asbestos dust exposure at work yield 25 fiber years, nor could bridge findings (e.g., plaques) be identified. In addition, the autopsies of 12 patients revealed plaques that had not been diagnosed during radiological examinations. These results show that - irrespective of the prescribed working techniques and radiological diagnosis - pathological/anatomical and histological diagnostics are often the only way for the insureds to demonstrate the causal connection between asbestos and their disease. Even after long intervals of up to 40 years post last exposure, the asbestos fibers would still be easily detectable in the lung tissues evaluated.

CONCLUSIONS: Whenever suitable tissue is available, it should be examined for mild asbestosis with the aid of a lung dust analysis. Otherwise there is a risk that an occupational disease is wrongfully rejected. In the context of health insurance, the lung dust analysis and the resulting proof of the presence of asbestosis often constitute one option of providing evidence of an occupational disease. Int J Occup Med Environ Health 2018;31(3):293-305.}, } @article {pmid29094504, year = {2018}, author = {Schelch, K and Kirschner, MB and Williams, M and Cheng, YY and van Zandwijk, N and Grusch, M and Reid, G}, title = {A link between the fibroblast growth factor axis and the miR-16 family reveals potential new treatment combinations in mesothelioma.}, journal = {Molecular oncology}, volume = {12}, number = {1}, pages = {58-73}, pmid = {29094504}, issn = {1878-0261}, mesh = {Cell Line, Tumor ; Down-Regulation ; Fibroblast Growth Factor 2/*therapeutic use ; Fibroblast Growth Factors/*metabolism ; Humans ; Lung Neoplasms/*drug therapy/*metabolism ; Mesothelioma/*drug therapy/*metabolism ; Mesothelioma, Malignant ; MicroRNAs/genetics/*metabolism ; Pleura/pathology ; Proto-Oncogene Proteins c-bcl-2/genetics/metabolism ; Receptors, Fibroblast Growth Factor/genetics/metabolism ; Recombinant Proteins/*therapeutic use ; Up-Regulation ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive malignancy with very limited therapeutic options. Fibroblast growth factor (FGF) signals play important roles in mesothelioma cell growth. Several FGFs and FGF receptors (FGFRs) are predicted targets of the miR-15/16 family, which is downregulated in MPM. The aim of this study was to explore the link between the miR-15/16 family and the FGF axis in MPM. Expression analyses via RT-qPCR showed downregulation of the FGF axis after transfection with miR-15/16 mimics. Direct interaction was confirmed by luciferase reporter assays. Restoration of miR-15/16 led to dose-dependent growth inhibition in MPM cell lines, which significantly correlated with their sensitivity to FGFR inhibition. Treatment with recombinant FGF2 prevented growth inhibition and further reduced the levels of FGF/R-targeting microRNAs, indicating a vicious cycle between miR-15/16 down- and FGF/FGFR signaling upregulation. Combined inhibition of two independent miR-15/16 targets, the FGF axis and Bcl-2, resulted in additive or synergistic activity. Our data indicate that post-transcriptional repression of FGF-mediated signals contributes to the tumor suppressor function of the microRNA-15/16 family. Inhibiting hyperactivated FGF signals and Bcl-2 might serve as a novel therapeutic combination strategy in MPM.}, } @article {pmid29086761, year = {2017}, author = {Buresti, G and Colonna, F and Corfiati, M and Valenti, A and Persechino, B and Marinaccio, A and Rondinone, BM and Iavicoli, S}, title = {Economic impact of malignant mesothelioma in Italy: an estimate of the public and social costs.}, journal = {La Medicina del lavoro}, volume = {108}, number = {5}, pages = {358-366}, doi = {10.23749/mdl.v108i5.6505}, pmid = {29086761}, issn = {0025-7818}, mesh = {Aged ; Aged, 80 and over ; *Cost of Illness ; Female ; *Health Care Costs ; Humans ; Italy ; Lung Neoplasms/*economics ; Male ; Mesothelioma/*economics ; Mesothelioma, Malignant ; Middle Aged ; Occupational Diseases/*economics ; Public Health/*economics ; }, abstract = {BACKGROUND: Despite their considerable interest for public health policies and for occupational disease management and assessment, the economic costs of asbestos-related diseases (ARDs) for society have not been fully estimated or even frequently discussed.

OBJECTIVES: The aim of this study was to estimate the economic burden of mesothelioma in Italy by assessing the overall societal cost of the disease, applying an econometric model.

METHODS: We analyzed two main cost groups, public and social. The first includes expenditure borne by the State and other public bodies (medical care costs, insurance, tax and benefits), while the latter uses the human capital approach to measure the loss of productivity suffered by the economy as a whole.

RESULTS: We provide an estimate of euro 33,000 per patient for medical care costs and euro 25,000 for insurance and compensation; tax and benefits seem to roughly compensate. We estimated a loss of more than euro 200,000 per patient, in terms of loss of production.

CONCLUSIONS: This study offers a practical approach for estimating the economic impact of mesothelioma, and provides empirical evidence of the huge economic burden linked to this disease, with its high etiologic fraction.}, } @article {pmid29085453, year = {2017}, author = {Kim, YR and Song, MH and Lee, JW and Bae, JH and Kim, JE and Kang, DM and Lee, SY}, title = {Identification of tumor antigens in malignant mesothelioma.}, journal = {Oncology letters}, volume = {14}, number = {4}, pages = {4557-4562}, pmid = {29085453}, issn = {1792-1074}, abstract = {Serological analysis of recombinant tumor cDNA expression library (SEREX) is a powerful and widely used method to explore the cancer immune environment. In the present study, immunoscreening of normal testicular tissues and malignant mesothelioma (MM) cancer MSTO-211H cell line cDNA libraries with sera from 5 MM patients led to the isolation of 16 independent antigens, which were designated 'Korea Pusan-Malignant Mesothelioma' (KP-MM)-1 to -16. In total, 3/16 antigens were identified using the results of previous SEREX analyses, and 13 were newly identified. Of these, KP-MM-8, which was subsequently identified as amyotrophic lateral sclerosis 2 chromosome region candidate 11, was shown to be tissue-restricted. Reverse transcription-polymerase chain reaction demonstrated KP-MM-8 to be expressed strongly only in the normal testis, and weakly in the spleen, prostate, ovary, heart and skeletal muscle. In addition, KP-MM-8 mRNA was identified in MM cell lines, and in various other cancer cell lines, including MM (3/4), lung cancer (5/7), melanoma (5/7) and liver cancer (5/5) cell lines. Additionally, 2/16 antigens (KP-MM-2 and KP-MM-6) exclusively reacted with sera from cancer patients. However, KP-MM-8 reacted with 1 of 8 MM sera. Notably, 8/8 patients with MM and 8/8 normal individuals exhibited antibodies reactive to KP-MM-5, which was identified as cell division cycle 25B, a known oncogene. Overall, this data suggests that KP-MM-8 may be considered as a cancer/testis-like antigen and KP-MM-5 as an immunogenic tumor antigen in MM patients.}, } @article {pmid29084128, year = {2017}, author = {Mangone, L and Di Felice, E and Storchi, C and Romanelli, A and Broccoli, S and Vicentini, M and Giorgi Rossi, P}, title = {The effects of improving the mesothelioma surveillance network on sensitivity, timeliness in reporting and asbestos exposure assessment.}, journal = {La Medicina del lavoro}, volume = {108}, number = {5}, pages = {367-376}, doi = {10.23749/mdl.v108i5.5929}, pmid = {29084128}, issn = {0025-7818}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; *Epidemiological Monitoring ; Female ; Humans ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology/*etiology ; Middle Aged ; Occupational Exposure/*statistics & numerical data ; Registries/*statistics & numerical data ; Sensitivity and Specificity ; Time Factors ; }, abstract = {BACKGROUND: In Italy, Mesothelioma Registries (MRs) have been established by law for the epidemiological surveillance of occupational cancers. MRs collect information about asbestos exposure of incident cases, through interviews. In the Emilia-Romagna region, MR was implemented in 1996 and extended its network of health professionals who report suspected mesothelioma in 2001 and 2007.

OBJECTIVES: This study evaluated the impact of the extension of the network on MR sensitivity and timeliness.

METHODS: Mesothelioma cases were analysed in three subsequent periods: 1996-2001 (before any network extension), 2002-2007 (after first extension) and 2008-2014 (after second extension). Sensitivity was evaluated by the proportion of cases directly reported by the network out of the total number of incident cases; reporting and interview timeliness were assessed by median times between diagnosis and, respectively, reporting and interview. Pleural mesothelioma reporting timeliness was also evaluated by use of quantile regression models, stratified by diagnostic certainty and adjusted by sex and age.

RESULTS: Sensitivity increased from 79.4% (1996-2001), to 89.0% (2002-2007) and to 91.4% (2008-2013). For mesothelioma with diagnostic certainty, we recorded considerably reduced reporting times from the 50th percentile on, whereas for uncertain mesothelioma relevant reductions were observed also in the lower percentiles. A reduced time to interview was observed too, which was more significant for uncertain cases. The proportion of patients directly interviewed increased from 33.5% (1996-2001), to 39.1% (2002-2007), to 49.5% (2008-2014).

CONCLUSIONS: The extended network improved the MR sensitivity and allowed shorter reporting and interview times and more frequent patient interviews, thus improving accuracy of exposure definition.}, } @article {pmid29083343, year = {2017}, author = {Chiesa, V and Odone, A and Signorelli, C}, title = {Forensic Epidemiology in Italy: principles and practice.}, journal = {Acta bio-medica : Atenei Parmensis}, volume = {88}, number = {3}, pages = {360-364}, pmid = {29083343}, issn = {2531-6745}, mesh = {*Epidemiology ; *Forensic Sciences ; Humans ; Italy ; }, abstract = {Forensic epidemiology (FE) implies the use of epidemiological data in the processes and the involvement of epidemiologists in judicial proceedings. FE is essential for the assessment of causal association between the exposure to specific agents and the occurrence of diseases. In this paper we describe FE principles and applications in the Italian context as in recent years FE emerged increasingly as well as the need of experienced and trained epidemiological experts able to navigate legal proceedings. In the literature, the principles of FE have been widely described by different authors, among them: Kennet Rothman who introduced the definition of cause, Sir Austin Bradford Hill who proposed an analytic framework to assess the causal association, and recently by Sana Loue who described the actual legislation and application of FE in the United States. Despite the legislation varies among different countries epidemiological methods and theories represent the foundation for the application of FE we illustrate in this paper. The association between environmental pollution and disease, mobile phones and cancer, vaccines and autism, asbestos and pleural mesothelioma are all situations that underscore the need for FE investigations in criminal acts. Causal association is a complex process: in real life only in limited cases causal associations are assessed by gathering robust scientific evidence, while cases with doubts and situations where different approaches to questions may lead to discordant arguments to questions may lead to discordant arguments are more frequent. Therefore, during the assessment of causation in civil and criminal matters the choice the epidemiological expert - with his knowledge and expertise - and the evidence from well-designed studies are crucial to fill the gaps between clinical and epidemiological data and the low.}, } @article {pmid29080447, year = {2017}, author = {Salo, SAS and Ilonen, I and Laaksonen, S and Myllärniemi, M and Salo, JA and Rantanen, T}, title = {Epidemiology of malignant peritoneal mesothelioma: A population-based study.}, journal = {Cancer epidemiology}, volume = {51}, number = {}, pages = {81-86}, doi = {10.1016/j.canep.2017.10.008}, pmid = {29080447}, issn = {1877-783X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Incidence ; Lung Neoplasms/*epidemiology/mortality/pathology ; Male ; Mesothelioma/*epidemiology/mortality/pathology ; Mesothelioma, Malignant ; Middle Aged ; Peritoneal Neoplasms/*epidemiology/mortality/pathology ; Registries ; Retrospective Studies ; Survival Analysis ; Young Adult ; }, abstract = {BACKGROUND: Malignant peritoneal mesothelioma (MPeM) is a rare cancer of the mesothelial cells in the peritoneum with poor prognosis. Earlier reports from other countries indicate an incidence of 0.2-3 new cases per million per year. No previous studies have examined the national epidemiology of MPeM in Nordic countries. This study aimed to clarify the epidemiology of MPeM in Finland over a 12-year period.

METHODS: The data consisted of cancer notifications, laboratory notifications, and death certificate information in the Finnish Cancer Registry (FCR) and Statistics Finland (SF) of all MPeM patients from 2000 to 2012 in Finland. We also collected data on occupational disease compensations from the Workers' Compensation Center (WCC) of Finland. Any missing information was collected from the respective patient's file of every patient obtained from health institutions that had treated the patients.

RESULTS: Between January 1, 2000 and December 31, 2012, 90 new MPeM cases (56 males, 34 females) occurred in Finland. Median annual incidence was four new cases, which corresponded to 0.74 new cases per million per year. MPeM was deemed an occupational disease in 21 patients (23.3%). 71 patients (78.9%) of whom had a known cause of death, with a median survival of 4 months. The number of deaths linked to other disease than mesothelioma was 28/74 (37.8%).

CONCLUSIONS: Our study indicates that MPeM in Finland is rare and fatal, which is in accordance with previous reports from other countries. MPeM is also a fatal disease, since most of the patients died due to MPeM.}, } @article {pmid29078648, year = {2017}, author = {Perikleous, P and Waller, DA}, title = {Video assisted thoracoscopic and open chest surgery in diagnosis and treatment of malignant pleural diseases.}, journal = {Journal of visualized surgery}, volume = {3}, number = {}, pages = {85}, pmid = {29078648}, issn = {2221-2965}, abstract = {Parenchymal cancers of lung, breast, gastrointestinal tract and ovaries as well as lymphomas and mesotheliomas are among the most common cancer types causing malignant effusions, though almost all tumour types have been reported to cause a malignant effusion. The prognosis heavily depends on patients' response to systemic therapy however, regardless of the causing pathology and histopathologic form, malignant pleural disease is normally associated with a poor prognosis. To date, there are not sufficient data to allow accurate predictions of survival that would facilitate decision making for managing patients with malignant pleural diseases. Interventions are directed towards drainage of the effusion and, when appropriate, concurrent or subsequent pleurodesis or establishing long-term drainage to prevent re-accumulation. The rate of re-accumulation of the pleural effusion, the patient's prognosis, and the severity of the patient's symptoms should guide the subsequent choice of therapy. In contemporary medicine, not many cancers have managed to generate as intense debates concerning treatment, as malignant pleural mesothelioma. The relative advantages of surgery, radiation, chemotherapy and any combination of the three are continuously reassessed and reconsidered, even though not always based on scientific evidence. The aim of surgery in mesothelioma may be prolongation of life, in addition to palliation of symptoms. Longer recovery periods from more extensive surgical procedures could be justified, in carefully selected patients. Surgical options include: Video assisted thoracoscopic (VATS) pleurodesis, VATS partial pleurectomy (VATS PP)-both parietal and visceral; open pleurectomy decortication (PD)-with an extended option (EPD) and extrapleural pneumonectomy (EPP). Current evidence implies that EPD can be performed reliably in specialised centres with good results, both in terms of mortality and survival; however, no operation has yet been shown to be beneficial in a prospective randomized controlled clinical trial.}, } @article {pmid29073511, year = {2017}, author = {Mensi, C and Mendola, M and Dallari, B and Sokooti, M and Tabibi, R and Riboldi, L and Consonni, D}, title = {Differences between peritoneal and pleural mesothelioma in Lombardy, Italy.}, journal = {Cancer epidemiology}, volume = {51}, number = {}, pages = {68-73}, doi = {10.1016/j.canep.2017.10.003}, pmid = {29073511}, issn = {1877-783X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Peritoneal Neoplasms/*epidemiology ; Pleural Neoplasms/*epidemiology ; Registries ; }, abstract = {BACKGROUND: We examined characteristics of peritoneal (PEM) and pleural (PLM) mesothelioma in Lombardy, Italy.

METHODS: From the Lombardy Mesothelioma Registry we selected PEM (N=300) and PLM (N=5011) cases diagnosed in 2000-2014. We investigated asbestos exposure and presence of asbestosis or pleural plaques.

RESULTS: Incidence rates (per 1,000,000 person-years, world standardized) of PEM were 1.2 (men) and 0.9 (women), compared with 22.6 and 8.4 for PLM. Asbestosis (both genders) and pleural plaques (men) were more frequent among PEM cases. Occupational asbestos exposure was similar in PEM and PLM cases. We found higher proportions of PEMs employed in the asbestos cement production.

CONCLUSION: The higher frequency of pleural plaques in PEM cases confirm the association between asbestos and peritoneal mesothelioma. The higher proportions of asbestosis and of past employment in the asbestos-cement sector among PEM cases suggest a possible role of high exposures to asbestos in the peritoneal mesothelioma genesis.}, } @article {pmid29072598, year = {2017}, author = {Lemen, RA and Landrigan, PJ}, title = {Toward an Asbestos Ban in the United States.}, journal = {International journal of environmental research and public health}, volume = {14}, number = {11}, pages = {}, pmid = {29072598}, issn = {1660-4601}, mesh = {Animals ; Asbestos/*history/toxicity ; Carcinogens/*history/toxicity ; Government Regulation ; History, 19th Century ; History, 20th Century ; Humans ; Occupational Exposure/*legislation & jurisprudence/*prevention & control ; United States ; }, abstract = {Many developed countries have banned the use of asbestos, but not the United States. There have, however, been multiple efforts in the US to establish strict exposure standards, to limit asbestos use, and to seek compensation through the courts for asbestos-injured workers' In consequence of these efforts, asbestos use has declined dramatically, despite the absence of a legally mandated ban. This manuscript presents a historical review of these efforts.}, } @article {pmid29072053, year = {2017}, author = {Emami, H and Ilbeigi, A and Khodadad, K}, title = {An Overview of Asbestos and Malignant Pleural Mesothelioma: An Iranian Perspective.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {18}, number = {10}, pages = {2619-2623}, pmid = {29072053}, issn = {2476-762X}, abstract = {Asbestos refers to a group of minerals that appears naturally in the environment as bundles of fibers. The incidence rate of asbestos-related diseases has considerably increased as well as the amount of asbestos utilization in few countries. Malignant pleural mesothelioma (MPM) is a rare type of aggressive and life threatening neoplasm which arise from various serous surfaces: pleura, peritoneum, tunica vaginalis and pericardium. The first case of MPM was reported in 1947. MPM etiologically is associated to the exposure of asbestos fibers. This form of malignancy is difficult to diagnose in paraclinical work-ups because mesothelioma could occur within 10-20 years of the first-time exposure to asbestos. The burden of MPM is not yet to be wholly understood. The toxic side effects of asbestos on environment and people compelled the European countries to accept the French view upon this matter. However, this approach has not been accepted by some developing countries. This review provides a brief points and facts in relation to MPM and asbestos in Iran.}, } @article {pmid29068368, year = {2017}, author = {Metintaş, S and Batırel, HF and Bayram, H and Yılmaz, Ü and Karadağ, M and Ak, G and Metintaş, M}, title = {Turkey National Mesothelioma Surveillance and Environmental Asbestos Exposure Control Program.}, journal = {International journal of environmental research and public health}, volume = {14}, number = {11}, pages = {}, pmid = {29068368}, issn = {1660-4601}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Environmental Exposure/*prevention & control ; Environmental Monitoring ; Female ; Humans ; Incidence ; Lung Neoplasms/chemically induced/*epidemiology ; Male ; Mesothelioma/chemically induced/*epidemiology ; Mesothelioma, Malignant ; Middle Aged ; *Population Surveillance ; Risk ; Rural Population/statistics & numerical data ; Turkey/epidemiology ; Young Adult ; }, abstract = {Malignant mesothelioma (MM) is an important health problem due to ongoing asbestos exposure. Environmental asbestos exposure leads to a high risk of MM in Turkey. The Turkish Mesothelioma Working Group and the Turkish Public Health Institute designed and performed the Turkey National Mesothelioma Surveillance and Environmental Asbestos Exposure Control Program (TUNMES-EAECP). The aim of this study was to analyze the results of the TUNMES-EAECP. Patients diagnosed with MM (code C45.0-C45.9) between 2008 and 2012 were identified. The "from case to the field" method was used to determine the villages with current or previous asbestos exposure. Special public health teams took soil samples from these villages, which were then examined using an X-ray diffractometer. Direct Standardized Average Annual Mesothelioma Incidence Rate (AMIR) and relative risk (RR) of MM were calculated. Finally, a projection on the incidence of MM between 2013 and 2033 was made. The number of confirmed MM cases was 5617 with a male to female ratio of 1.36. Mean age was 61.7 ± 13.4 (20-96) years. The median survival was eight (95% CI 7.6-8.4) months. Asbestos exposure continues in 379 villages, with 158,068 people still living in high risk areas. The standardized AMIR was 2.33/100,000 per year. The risk of MM was higher in males, in both sexes over the age of 40, in asbestos-containing provinces, and in those where the TUNMES was organized. Among the population with continuing asbestos exposure in rural areas, the number of MM cases between 2013 and 2033 was estimated as 2511. As such, the incidence of MM in Turkey is as high as in industrialized countries. Asbestos exposure in rural areas continues to be a serious problem in Turkey, which obviates the necessity for effective preventive measures.}, } @article {pmid29061909, year = {2018}, author = {Lacourt, A and Leveque, E and Goldberg, M and Leffondre, K}, title = {Dose-time response association between occupational asbestos exposure and pleural mesothelioma: authors' response.}, journal = {Occupational and environmental medicine}, volume = {75}, number = {2}, pages = {161-162}, doi = {10.1136/oemed-2017-104802}, pmid = {29061909}, issn = {1470-7926}, mesh = {*Asbestos ; Humans ; *Lung Neoplasms ; *Mesothelioma ; *Pleural Neoplasms ; }, } @article {pmid29059207, year = {2017}, author = {Alfaleh, MA and Howard, CB and Sedliarou, I and Jones, ML and Gudhka, R and Vanegas, N and Weiss, J and Suurbach, JH and de Bakker, CJ and Milne, MR and Rumballe, BA and MacDiarmid, JA and Brahmbhatt, H and Mahler, SM}, title = {Targeting mesothelin receptors with drug-loaded bacterial nanocells suppresses human mesothelioma tumour growth in mouse xenograft models.}, journal = {PloS one}, volume = {12}, number = {10}, pages = {e0186137}, pmid = {29059207}, issn = {1932-6203}, mesh = {Animals ; *Cell Proliferation ; Humans ; Mesothelin ; Mesothelioma/*pathology ; Mice ; Receptors, Cell Surface/*metabolism ; Xenograft Model Antitumor Assays ; }, abstract = {Human malignant mesothelioma is a chemoresistant tumour that develops from mesothelial cells, commonly associated with asbestos exposure. Malignant mesothelioma incidence rates in European countries are still rising and Australia has one of the highest burdens of malignant mesothelioma on a population basis in the world. Therapy using systemic delivery of free cytotoxic agents is associated with many undesirable side effects due to non-selectivity, and is thus dose-limited which limits its therapeutic potential. Therefore, increasing the selectivity of anti-cancer agents has the potential to dramatically enhance drug efficacy and reduce toxicity. EnGeneIC Dream Vectors (EDV) are antibody-targeted nanocells which can be loaded with cytotoxic drugs and delivered to specific cancer cells via bispecific antibodies (BsAbs) which target the EDV and a cancer cell-specific receptor, simultaneously. BsAbs were designed to target doxorubicin-loaded EDVs to cancer cells via cell surface mesothelin (MSLN). Flow cytometry was used to investigate cell binding and induction of apoptosis, and confocal microscopy to visualize internalization. Mouse xenograft models were used to assess anti-tumour effects in vivo, followed by immunohistochemistry for ex vivo evaluation of proliferation and necrosis. BsAb-targeted, doxorubicin-loaded EDVs were able to bind to and internalize within mesothelioma cells in vitro via MSLN receptors and induce apoptosis. In mice xenografts, the BsAb-targeted, doxorubicin-loaded EDVs suppressed the tumour growth and also decreased cell proliferation. Thus, the use of MSLN-specific antibodies to deliver encapsulated doxorubicin can provide a novel and alternative modality for treatment of mesothelioma.}, } @article {pmid29034666, year = {2017}, author = {Serrier, H and Sultan-Taïeb, H and Luce, D and Béjean, S}, title = {[Respiratory cancers attributable to occupational exposures: what is the cost to society in France].}, journal = {Sante publique (Vandoeuvre-les-Nancy, France)}, volume = {29}, number = {4}, pages = {509-524}, doi = {10.3917/spub.174.0509}, pmid = {29034666}, issn = {0995-3914}, mesh = {Female ; France/epidemiology ; Humans ; Male ; Occupational Diseases/*economics/epidemiology ; Occupational Exposure/*adverse effects/*economics ; Respiratory Tract Neoplasms/chemically induced/*economics/epidemiology ; Risk Factors ; }, abstract = {OBJECTIVE: To estimate the social cost of respiratory cancers attributable to occupational risk factors in France in 2010.

METHODS: We estimated the number of cases of respiratory cancers attributable to each identified occupational risk factor according to the attributable fractions method. We also estimated direct (costs of hospital stays, drugs, outpatient care) and indirect costs (production losses) related to morbidity (absenteeism and presenteeism) and mortality (years of lost production). Production losses for paid work and unpaid domestic activities were taken into account.

RESULTS: The social cost of respiratory cancers (lung, larynx, sinonasal, pleural mesothelioma) attributable to exposure to asbestos, chromium, diesel engine exhaust, polycyclic aromatic hydrocarbons, painting occupations (unidentified carcinogen), crystalline silica, wood and leather dust in France in 2010 was estimated to be between €960 and 1,866 million. The cost of lung cancer represents between €804 and 1,617 million. The three risk factors with the greatest impact are asbestos (€530 to 890 million), diesel engine exhaust (€227 to 394 million), and crystalline silica (€116 to 268 million).

CONCLUSION: These results provide a conservative estimate of the public health and economic burden of respiratory cancers attributable to occupational risk factors from a societal perspective.}, } @article {pmid29030093, year = {2018}, author = {Cherrie, JW and McElvenny, D and Blyth, KG}, title = {Estimating past inhalation exposure to asbestos: A tool for risk attribution and disease screening.}, journal = {International journal of hygiene and environmental health}, volume = {221}, number = {1}, pages = {27-32}, doi = {10.1016/j.ijheh.2017.09.013}, pmid = {29030093}, issn = {1618-131X}, support = {ETM/285/CSO_/Chief Scientist Office/United Kingdom ; }, mesh = {Asbestos/*administration & dosage ; Humans ; Inhalation Exposure/*analysis ; Risk Assessment ; }, abstract = {INTRODUCTION: Late presentation is common in mesothelioma. Reliable assessment of past exposure to asbestos is a necessary first step for risk attribution and for the development of a future screening programme. Such a programme could maximise access to trials of novel therapies and would pave the way for development of novel chemoprophylaxis strategies. This paper describes a method for individual exposure reconstruction along with data from a validation study.

METHODS: The exposure assessment method uses only descriptive information about the circumstances of the work that could be obtained from questioning the worker. The assessment is based on the tasks carried out and includes parameters for substance emission potential, activity emission potential, the effectiveness of any local control measures, passive emission, the fractional time the asbestos source is active and the efficiency of any respiratory protection worn.

RESULTS: There was a good association between the estimated and measured exposure levels. Pearson's correlation coefficient between the log-transformed measurements and estimates from the model was 0.86, and 95% of the estimated individual values were within about a factor of ten of the associated measured value. The method described would be suitable for pre-selecting individuals at high risk of malignant pleural mesothelioma for screening using appropriate tools and/or enrolment in clinical trials of chemo-prophylaxis.

DISCUSSION: This method is of potential clinical value in developing novel treatment approaches for mesothelioma. Pilot studies to test this approach are urgently needed.}, } @article {pmid29020669, year = {2017}, author = {Gogali, A and Ntzani, EE and Manda-Stachouli, C and Peristeri, S and Tzarouchi, L and Laiou, E and Konstantinidis, A and Constantopoulos, SH and Dalavanga, Y}, title = {Evidence Suggesting the End of Universal Domestic Asbestos Exposure in Metsovo, NW Greece.}, journal = {Respiration; international review of thoracic diseases}, volume = {94}, number = {6}, pages = {510-517}, doi = {10.1159/000480151}, pmid = {29020669}, issn = {1423-0356}, mesh = {Adult ; Asbestos/adverse effects/*analysis ; Asbestosis/*diagnostic imaging ; Bronchoalveolar Lavage Fluid/chemistry ; Calcinosis/diagnostic imaging/*etiology ; Environmental Exposure/adverse effects/*analysis ; Female ; Greece/epidemiology ; Humans ; Male ; Mesothelioma/epidemiology/etiology ; Middle Aged ; Radiography, Thoracic ; Tomography, X-Ray Computed ; }, abstract = {BACKGROUND: Inhabitants of Metsovo, NW Greece, had been domestically exposed to asbestos from a gradually abandoned whitewash ("luto") that resulted in a declining epidemic of malignant mesothelioma.

OBJECTIVES: We aimed to evaluate whether other sources of asbestos exposure exist following "luto" abandonment.

METHODS: Chest computed tomography (CT) and bronchoalveolar lavage (BAL) were used to evaluate residual asbestos exposure in younger Metsovites through the identification of pleural calcifications and asbestos bodies, respectively. In order to provide a historical universally exposed group for comparison, we used the accumulated chest CTs and chest roentgenograms of our previous studies, performed in Metsovites with confirmed exposure but negative chest roentgenogram. As an additional external comparison group, we also assessed CT scans and chest roentgenograms of Metsovites being older than our target group obtained from the records of the Radiology Department between 2009 and 2011. In order to be able to compare our BAL findings, we sought historical controls among BAL studies performed in Metsovites with known exposure to "luto," in the 1980s-1990s, mainly to evaluate alveolitis. Those belonging to individuals of the same age range were used for further comparison.

RESULTS: Twenty-two Metsovites born between 1960 and 1980 consented to undergo a chest CT scan, while another 14 CTs were retrieved from the records of the Radiology Department (among 86 of all ages), thus increasing the number of individuals studied to 36. Five of the 36 Metsovites studied were former "luto" users for a short period of time. Minimal pleural calcifications were present in 2 of them, while all chest CTs of nonusers were negative. All 8 BAL studies were negative for asbestos bodies.

CONCLUSION: "Luto" use seems to have been the only source of considerable asbestos exposure in Metsovo.}, } @article {pmid28986649, year = {2017}, author = {Tischoff, I and Tannapfel, A}, title = {[Mesothelioma].}, journal = {Der Pathologe}, volume = {38}, number = {6}, pages = {547-560}, pmid = {28986649}, issn = {1432-1963}, mesh = {Asbestos/adverse effects ; Female ; Germany ; Humans ; *Lung Neoplasms/etiology/pathology ; Male ; *Mesothelioma/etiology/pathology ; Middle Aged ; Risk Factors ; }, abstract = {Malignant mesotheliomas are rare and aggressive tumours arising from mesothelial cells of the pleura and peritoneum. Infrequent sites of origin are the pericardium and tunica vaginalis testis. More than 80% of mesotheliomas are localized in the pleura. Men are more frequently affected than women. The median age is >60 years. Asbestos exposure is the best known aetilogical risk factor and is reported in 54-90% of patients. In Germany, malignant mesotheliomas caused by occupational asbestos exposure are compensated as occupational disease since 1977. Several neoplastic and non-neoplastic lesions like metastasis, sarcomas, lymphomas or pleuritis with reactive mesothelial proliferation have to be distinguished from malignant mesotheliomas. Especially, the pathohistological differentiation between atypical reactive mesothelial proliferation from malignant mesothelioma is a diagnostic challenge.}, } @article {pmid28985440, year = {2017}, author = {Binazzi, A and Marinaccio, A and Corfiati, M and Bruno, C and Fazzo, L and Pasetto, R and Pirastu, R and Biggeri, A and Catelan, D and Comba, P and Zona, A}, title = {Mesothelioma incidence and asbestos exposure in Italian national priority contaminated sites.}, journal = {Scandinavian journal of work, environment & health}, volume = {43}, number = {6}, pages = {550-559}, doi = {10.5271/sjweh.3676}, pmid = {28985440}, issn = {1795-990X}, mesh = {Asbestos/*toxicity ; Bayes Theorem ; Environmental Exposure/statistics & numerical data ; Female ; Humans ; Incidence ; Italy/epidemiology ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology ; Mesothelioma, Malignant ; Occupational Exposure/*statistics & numerical data ; Registries/*statistics & numerical data ; }, abstract = {Objectives This study aimed to (i) describe mesothelioma incidence in the Italian national priority contaminated sites (NPCS) on the basis of data available from the Italian National Mesothelioma Registry (ReNaM) and (ii) profile NPCS using Bayesian rank analysis. Methods Incident cases of mesothelioma and standardized incidence ratios (SIR) were estimated for both genders in each of the 39 selected NPCS in the period 2000-2011. Age-standardized rates of Italian geographical macro areas were used to estimate expected cases. Rankings of areas were produced by a hierarchical Bayesian model. Asbestos exposure modalities were discussed for each site. Results In the study period, 2683 incident cases of mesothelioma (1998 men, 685 women) were recorded. An excess of mesothelioma incidence was confirmed in sites with a known past history of direct use of asbestos (among men) such as Balangero (SIR 197.1, 95% CI 82.0-473.6), Casale Monferrato (SIR 910.7, 95% CI 816.5-1012.8), and Broni (SIR 1288.5, 95% CI 981.9-1691.0), in sites with shipyards and harbors (eg, Trieste, La Spezia, Venice, and Leghorn), and in settings without documented direct use of asbestos. The analysis ranked the sites of Broni and Casale Monferrato (both genders) and Biancavilla (only for women) the highest. Conclusions The present study confirms that asbestos pollution is a risk for people living in polluted areas, due to not only occupational exposure in industrial settings with direct use of asbestos but also the presence of asbestos in the environment. Epidemiological surveillance of asbestos-related diseases is a fundamental tool for monitoring the health profile in NPCS.}, } @article {pmid28984470, year = {2017}, author = {Sobhani, N and Corona, SP and Bonazza, D and Ianza, A and Pivetta, T and Roviello, G and Cortale, M and Guglielmi, A and Zanconati, F and Generali, D}, title = {Advances in systemic therapy for malignant mesothelioma: future perspectives.}, journal = {Future oncology (London, England)}, volume = {13}, number = {23}, pages = {2083-2101}, doi = {10.2217/fon-2017-0224}, pmid = {28984470}, issn = {1744-8301}, mesh = {Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use ; Clinical Trials as Topic ; Combined Modality Therapy ; Humans ; Immunotherapy ; Lung Neoplasms/mortality/pathology/*therapy ; Mesothelioma/mortality/pathology/*therapy ; Mesothelioma, Malignant ; Molecular Targeted Therapy ; Treatment Outcome ; }, abstract = {Malignant mesothelioma is a rare and aggressive form of cancer affecting the mesothelium. This mainly occupational disease is becoming more common in those countries where asbestos has been used for industrial applications. Notwithstanding the progress made in the field, patients do not survive more than 12 months on average with standard treatment. With the advent of next generation sequencing, it is now possible to study the mutational landscape of each tumor with the aim of identifying the genetic aberrations driving tumorigenesis. This review encompasses the latest research in the field, with particular attention to new chemotherapy combinatorial regimens, molecular targets and immunotherapies, providing a comprehensive picture of the current and future treatment options for malignant mesothelioma patients.}, } @article {pmid28979837, year = {2017}, author = {Ju, L and Wu, W and Yin, X and Xiao, Y and Jia, Z and Lou, J and Yu, M and Ying, S and Chen, T and Jiang, Z and Li, W and Chen, J and Zhang, X and Zhu, L}, title = {miR-30d is related to asbestos exposure and inhibits migration and invasion in NCI-H2452 cells.}, journal = {FEBS open bio}, volume = {7}, number = {10}, pages = {1469-1479}, pmid = {28979837}, issn = {2211-5463}, abstract = {Pleural malignant mesothelioma (MM) is a highly aggressive tumor that is typically related to asbestos exposure and has a latency of 20-60 years. Several microRNA contribute to MM initiation and progression, but the mechanisms are not clear. Here, we found that miR-30d is downregulated in the pleural MM cell line NCI-H2452, in the plasma of asbestos-exposed individuals, and in asbestos-exposed mesothelial cells. Furthermore, we investigated the influence of the overexpression of miR-30d in pleural MM cells. We demonstrated that miR-30d overexpression could suppress pleural MM cell proliferation, migration, and invasion in vitro and could promote cell apoptosis but could not significantly influence cell cycle. The mRNA and protein expression of vimentin and TWIST1 decreased, and the mRNA expression of CDH1 increased in NCI-H2452 cells that overexpressed miR-30d. We therefore conclude that miR-30d is related to asbestos exposure and inhibits cell migration and invasion by regulating the epithelial-mesenchymal transition in NCI-H2452 cells.}, } @article {pmid28960945, year = {2017}, author = {Yamaji, M and Ota, A and Wahiduzzaman, M and Karnan, S and Hyodo, T and Konishi, H and Tsuzuki, S and Hosokawa, Y and Haniuda, M}, title = {Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells.}, journal = {Cancer medicine}, volume = {6}, number = {11}, pages = {2646-2659}, pmid = {28960945}, issn = {2045-7634}, mesh = {Antineoplastic Agents/*pharmacology ; Apoptosis/drug effects ; Benzylamines/pharmacology ; Caspase 3/metabolism ; Caspase 7/metabolism ; Cell Line, Tumor ; Cyclin-Dependent Kinase Inhibitor p21/metabolism ; Forkhead Box Protein O1/metabolism ; G1 Phase Cell Cycle Checkpoints/drug effects ; Gene Expression Regulation, Neoplastic/drug effects ; Glycogen Synthase Kinase 3 beta/metabolism ; Heterocyclic Compounds, 3-Ring/pharmacology ; Heterocyclic Compounds, 4 or More Rings/pharmacology ; Humans ; Imidazoles ; Inhibitory Concentration 50 ; Mesothelioma/*drug therapy ; Oxadiazoles/pharmacology ; Phosphorylation/drug effects ; Phosphorylcholine/analogs & derivatives/pharmacology ; Pleural Neoplasms/*drug therapy ; Protein Kinase Inhibitors/*pharmacology ; Proto-Oncogene Proteins c-akt/*antagonists & inhibitors/metabolism ; Pyrazoles/*pharmacology ; Pyridines ; Pyrimidines/pharmacology ; Pyrroles/pharmacology ; Quinoxalines/pharmacology ; Sulfonamides/pharmacology ; Thiadiazoles/pharmacology ; Thiophenes/*pharmacology ; }, abstract = {Malignant pleural mesothelioma (MPM), an asbestos-related occupational disease, is an aggressive and incurable tumor of the thoracic cavity. Despite recent advances in MPM treatment, overall survival of patients with MPM is very low. Recent studies have implicated that PI3K/Akt signaling is involved in MPM cell survival and development. To investigate the effects of Akt inhibitors on MPM cell survival, we examined the effects of nine selective Akt inhibitors, namely, afuresertib, Akti-1/2, AZD5363, GSK690693, ipatasertib, MK-2206, perifosine, PHT-427, and TIC10, on six MPM cell lines, namely, ACC-MESO-4, Y-MESO-8A, MSTO-211H, NCI-H28, NCI-H290, and NCI-H2052, and a normal mesothelial cell line MeT-5A. Comparison of IC50 values of the Akt inhibitors showed that afuresertib, an ATP-competitive specific Akt inhibitor, exerted tumor-specific effects on MPM cells. Afuresertib significantly increased caspase-3 and caspase-7 activities and apoptotic cell number among ACC-MESO-4 and MSTO-211H cells. Moreover, afuresertib strongly arrested the cell cycle in the G1 phase. Western blotting analysis showed that afuresertib increased the expression of p21[WAF][1/][CIP][1] and decreased the phosphorylation of Akt substrates, including GSK-3β and FOXO family proteins. These results suggest that afuresertib-induced p21 expression promotes G1 phase arrest by inducing FOXO activity. Furthermore, afuresertib significantly enhanced cisplatin-induced cytotoxicity. Interestingly, results of gene set enrichment analysis showed that afuresertib modulated the expression E2F1 and MYC, which are associated with fibroblast core serum response. Together, these results suggest that afuresertib is a useful anticancer drug for treating patients with MPM.}, } @article {pmid28960045, year = {2017}, author = {Kim, JS and Lim, SY and Hwang, J and Kang, EJ and Choi, YJ}, title = {A Case Report of Primary Pericardial Malignant Mesothelioma Treated with Pemetrexed and Cisplatin.}, journal = {Journal of Korean medical science}, volume = {32}, number = {11}, pages = {1879-1884}, pmid = {28960045}, issn = {1598-6357}, mesh = {Aged ; Antineoplastic Agents/*therapeutic use ; Calbindin 2/metabolism ; Cardiac Tamponade/diagnosis ; Cisplatin/*therapeutic use ; Drug Therapy, Combination ; Female ; Humans ; Keratins/metabolism ; Lung Neoplasms/diagnosis/*drug therapy ; Mesothelioma/diagnosis/*drug therapy ; Mesothelioma, Malignant ; Pemetrexed/*therapeutic use ; Pleural Neoplasms/diagnosis/*drug therapy ; Thorax/diagnostic imaging ; Tomography, X-Ray Computed ; Treatment Outcome ; Ultrasonography ; Vimentin/metabolism ; }, abstract = {Primary pericardial malignant mesothelioma (PPM) is a very rare malignancy, with an incidence of less than 0.002% and represents less than 5% of all mesotheliomas. The cause of pericardial mesothelioma is uncertain that differ from pleural mesothelioma which is associated with asbestos exposure. This malignancy is terribly aggressive and has very poor prognosis with less than six months of overall survival. We present a case of a 71-year-old woman who was diagnosed with cardiac tamponade caused by PPM and received chemotherapy with pemetrexed and cisplatin for six months. During two years she was alive without disease progression. To better understand the clinical, pathologic features and treatment outcome of this entity, we reviewed 23 cases described in the English literature from 2009, together with our case, provided a total of 24 cases. Based on this review, we suggest that PPM must be considered in patients who have unexplained massive pericardial effusion and recommend chemotherapy with pemetrexed and cisplatin for the better outcome of PPM.}, } @article {pmid28951802, year = {2017}, author = {MacLeod, JS and Harris, MA and Tjepkema, M and Peters, PA and Demers, PA}, title = {Cancer Risks among Welders and Occasional Welders in a National Population-Based Cohort Study: Canadian Census Health and Environmental Cohort.}, journal = {Safety and health at work}, volume = {8}, number = {3}, pages = {258-266}, pmid = {28951802}, issn = {2093-7911}, abstract = {BACKGROUND: Welders are exposed to many known and suspected carcinogens. An excess lung cancer risk among welders is well established, but whether this is attributable to welding fumes is unclear. Excess risks of other cancers have been suggested, but not established. We investigated welding cancer risks in the population-based Canadian Census Health and Environmental Cohort.

METHODS: Among 1.1 million male workers, 12,845 welders were identified using Standard Occupational Classification codes and followed through retrospective linkage of 1991 Canadian Long Form Census and Canadian Cancer Registry (1992-2010) records. Hazard ratios (HRs) were calculated using Cox proportional hazards models based on estimated risks of lung cancer, mesothelioma, and nasal, brain, stomach, kidney, and bladder cancers, and ocular melanoma. Lung cancer histological subtypes and risks by industry group and for occasional welders were examined. Some analyses restricted comparisons to blue-collar workers to minimize effects of potential confounders.

RESULTS: Among welders, elevated risks were observed for lung cancer [HR: 1.16, 95% confidence interval (CI): 1.03-1.31], mesothelioma (HR: 1.78, 95% CI: 1.01-3.18), bladder cancer (HR: 1.40, 95% CI: 1.15-1.70), and kidney cancer (HR: 1.30, 95% CI: 1.01-1.67). When restricted to blue-collar workers, lung cancer and mesothelioma risks were attenuated, while bladder and kidney cancer risks increased.

CONCLUSION: Excess risks of lung cancer and mesothelioma may be partly attributable to factors including smoking and asbestos. Welding-specific exposures may increase bladder and kidney cancer risks, and particular sources of exposure should be investigated. Studies that are able to disentangle welding effects from smoking and asbestos exposure are needed.}, } @article {pmid28949000, year = {2018}, author = {Jiang, Z and Chen, T and Chen, J and Ying, S and Gao, Z and He, X and Miao, C and Yu, M and Feng, L and Xia, H and Wu, W and Chen, R and Morinaga, K and Lou, J and Zhang, X}, title = {Hand-spinning chrysotile exposure and risk of malignant mesothelioma: A case-control study in Southeastern China.}, journal = {International journal of cancer}, volume = {142}, number = {3}, pages = {514-523}, doi = {10.1002/ijc.31077}, pmid = {28949000}, issn = {1097-0215}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos, Serpentine/*poisoning ; Case-Control Studies ; China/epidemiology ; Female ; Humans ; Logistic Models ; Lung Neoplasms/*epidemiology/etiology ; Male ; Mesothelioma/*epidemiology/etiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Diseases/*epidemiology/etiology ; Occupational Exposure/*statistics & numerical data ; Retrospective Studies ; Risk ; Textile Industry/statistics & numerical data ; }, abstract = {While chrysotile has been commonly used by Chinese textile industry for many years, investigations on the association of chrysotile exposure with risk of mesothelioma in China are scarce. We conducted a case-control study in a county located at Southeastern China, including 46 cases and 230 individually matched controls. A semi-quantitative method based on experts' assessment was used for evaluating hand-spinning chrysotile exposure. Conditional logistic regression models were used to assess the association of asbestos exposure with risk of mesothelioma. We found that hand-spinning chrysotile exposure was associated with significantly elevated risk of mesothelioma, reaching OR =10 (95% CIs: 1.4-65) for possible exposure and 64 (12-328) for definite exposure. Our data suggested a dose-response relationship of chrysotile exposure duration with risk of mesothelioma, reaching 28 (6-134) for <6 years, 51 (11-247) for 7-17 years and 56 (9-351) for ≥18 years. A dose-response relationship of cumulative exposure index (CEI) with risk of mesothelioma was found, reaching 28 (6-137) for CEI at 0-0.5 fibers per milliliter years (f/mL-year), 36 (7-184) for CEI at 0.5-28.6 f/mL-years and 79 (14-451) for CEI > 28.6 f/mL-years. We found a dose-response relationship of chrysotile exposure duration and CEI with risk of mesothelioma in Southeastern China, adding valuable information on health hazards of chrysotile exposure in China where chrysotile is still used nationwide.}, } @article {pmid28947868, year = {2017}, author = {Zhao, J and Zuo, T and Zheng, R and Zhang, S and Zeng, H and Xia, C and Yang, Z and Chen, W}, title = {Epidemiology and trend analysis on malignant mesothelioma in China.}, journal = {Chinese journal of cancer research = Chung-kuo yen cheng yen chiu}, volume = {29}, number = {4}, pages = {361-368}, pmid = {28947868}, issn = {1000-9604}, abstract = {OBJECTIVE: Population-based cancer registration data were used to analyze the epidemiology and trend of malignant mesothelioma in China, and the result would provide basic data for its prevention and control.

METHODS: Malignant mesothelioma data in 2013 were retrieved from the database of National Cancer Registry. Malignant mesothelioma incidence and mortality were estimated using age-specific rate by urban/rural and gender according to the national population in 2013. Malignant mesothelioma data from 22 cancer registries were used for trend analysis during 2000-2013.

RESULTS: It is estimated that there were 2,041 new malignant mesothelioma cases and 1,659 malignant mesothelioma deaths occurred in 2013. The crude incidence rate in China were 1.50/10[6] (males 1.67/10[6], females 1.32/10[6]), age-standardized incidence rates by Chinese standard population (ASIRC) and by world standard population (ASIRW) were 1.03/10[6] and 1.02/10[6], respectively. The crude mortality rate in China was 1.22/10[6] (males 1.67/10[6], females 1.32/10[6]), age-standardized mortality rates by Chinese standard population (ASMRC) and by world standard population (ASMRW) were 0.83/10[6] and 0.81/10[6], respectively. There was an increasing trend of incidence rate for malignant mesothelioma in registration areas of China during 2000-2013 with annual percentage change (APC) of 2.5% [95% confidence interval (95% CI): 0.6%-4.5%]. After age standardization, no significant differences were observed. No matter for crude mortality rates or age-standardized mortality rates, no significant differences were observed during 2000-2013.

CONCLUSIONS: Malignant mesothelioma is the major occupational and environmental neoplasm associated with asbestos exposure. The increasing incidence trend suggests that more attention should be paid on this disease.}, } @article {pmid28947493, year = {2017}, author = {Landrigan, PJ}, title = {Data on mesothelioma mortality: a powerful tool for preventing asbestos-related disease.}, journal = {Occupational and environmental medicine}, volume = {74}, number = {12}, pages = {849-850}, doi = {10.1136/oemed-2017-104688}, pmid = {28947493}, issn = {1470-7926}, mesh = {Asbestos/adverse effects ; Female ; Humans ; Male ; Mesothelioma/*mortality/*prevention & control ; Occupational Exposure/adverse effects/statistics & numerical data ; }, } @article {pmid28940402, year = {2017}, author = {Kradin, RL and Eng, G and Christiani, DC}, title = {Diffuse peritoneal mesothelioma: A case series of 62 patients including paraoccupational exposures to chrysotile asbestos.}, journal = {American journal of industrial medicine}, volume = {60}, number = {11}, pages = {963-967}, doi = {10.1002/ajim.22768}, pmid = {28940402}, issn = {1097-0274}, mesh = {Aged ; Aged, 80 and over ; Asbestos, Serpentine/*toxicity ; Carcinogens/*toxicity ; Female ; Humans ; Male ; Mesothelioma/*etiology/pathology ; Middle Aged ; Occupational Exposure/*adverse effects/legislation & jurisprudence ; Peritoneal Neoplasms/*etiology/pathology ; Time Factors ; }, abstract = {BACKGROUND: Diffuse peritoneal malignant mesothelioma (DPM) is caused by exposure to asbestos. The medical literature has linked DPM primarily to high levels of asbestos exposure, in particular amosite. Controversy persists as to whether chrysotile is capable of causing DPM, especially when exposures are paraoccupational.

METHODS: Sixty-two subjects (51 men, 11 women) with DPM were reviewed in medical-legal consultation with deposition and product identification evidence.

RESULTS: All had pathologically confirmed DPM. Most were exposed to both amphibole and chrysotile, but chrysotile alone was documented in 14/62 (26%) cases. A total of 7/14 (50%) cases of the paraoccupational exposures were to chrysotile alone. Women were younger than men as were those with paraoccupational versus those with occupational exposure. The mean duration of exposure for all cases was 17.9 ± 10 years and latency from time of first exposure was 45.9 + 11.6 years.

CONCLUSIONS: DPM occurs with both occupational and paraoccupational exposures to asbestos and may be seen in paraoccupational exposures to chrysotile asbestos.}, } @article {pmid28937307, year = {2017}, author = {Møller, P and Jacobsen, NR}, title = {Weight of evidence analysis for assessing the genotoxic potential of carbon nanotubes.}, journal = {Critical reviews in toxicology}, volume = {47}, number = {10}, pages = {867-884}, doi = {10.1080/10408444.2017.1367755}, pmid = {28937307}, issn = {1547-6898}, mesh = {*DNA Damage ; Hazardous Substances/*toxicity ; Humans ; Mutagenicity Tests ; Nanotubes, Carbon/*toxicity ; }, abstract = {Carbon nanotube (CNT) is a nanomaterial that has received interest because of its high-tensile strength and low weight. Although CNTs differ substantially in physico-chemical properties, they share high aspect ratio which resembles that of asbestos and other fibers causing lung cancer and mesothelioma. One type of multi-walled CNTs (i.e. MWCNT-7) has been classified as possibly carcinogenic to humans by IARC (Group 2B) based on experimental animal data, whereas other types of MWCNTs and single-walled CNTs (SWCNT) could not be classified due to lack of data from epidemiologic studies and insufficient mechanistic evidence. Damage to DNA is considered to be a key mechanistic step in the development of fiber-induced cancer. Thus, the genotoxic potential can be a cornerstone in the evaluation of hazards of CNTs. The present study used a weight of evidence (WoE) analysis to evaluate the genotoxicity of different types of CNTs. Genotoxicity endpoints close to cancer (mutations and chromosome aberrations) and animal models had highest weight in the WoE analysis. Eight CNT materials out of 130, which had been assessed in several studies, were evaluated in the WoE analysis. The results demonstrated that MWCNT-7 has strongest WoE for a genotoxic hazard among the MWCNTs. Two types of SWCNTs have a similar WoE for genotoxicity as MWCNT-7. Several reference materials from the Joint Research Centre have less WoE for genotoxicity. The WoE analysis demonstrates a difference in genotoxicity for CNTs, but further research is required to unravel the physico-chemical characteristics that govern the differences in genotoxic hazard.}, } @article {pmid28935666, year = {2017}, author = {Marsh, GM and Riordan, AS and Keeton, KA and Benson, SM}, title = {Non-occupational exposure to asbestos and risk of pleural mesothelioma: review and meta-analysis.}, journal = {Occupational and environmental medicine}, volume = {74}, number = {11}, pages = {838-846}, doi = {10.1136/oemed-2017-104383}, pmid = {28935666}, issn = {1470-7926}, mesh = {Asbestos/*adverse effects ; Asbestos, Serpentine/adverse effects ; Environmental Exposure/*adverse effects/analysis ; Female ; *Housing ; Humans ; Lung Neoplasms/*chemically induced ; Male ; Mesothelioma/*chemically induced ; Mesothelioma, Malignant ; Occupational Exposure ; Pleural Neoplasms/*chemically induced ; *Residence Characteristics ; Risk Assessment ; }, abstract = {OBJECTIVE: To conduct an updated literature review and meta-analysis of studies of pleural malignant mesothelioma (PMM) risk among persons exposed to asbestos non-occupationally (household and neighbourhood).

METHODS: We performed a literature search for articles available in the National Center for Biotechnology Information's PubMed database published between 1967 and 2016. Meta-analyses were conducted to calculate pooled PMM risk estimates, stratifying for household or neighbourhood exposure to asbestos and/or predominant asbestos fibre type (chrysotile, amphibole or mixed).

RESULTS: Eighteen studies in 12 countries comprising 665 cases met the meta-analysis inclusion criteria. We identified 13 estimates of PMM risk from neighbourhood exposures, 10 from household and one from mixed exposure, and combined the estimates using random-effects models. The overall meta-relative risk (meta-RR) was 5.9 (95% CI 4.4 to 8.7). The meta-RRs for household and neighbourhood exposures were 5.4 (95% CI 2.6 to 11.2) and 6.9 (95% CI 4.2 to 11.4), respectively. We observed trends in risk in relation to fibre type for both household and neighbourhood studies. For chrysotile, mixed and amphibole fibres, respectively, meta-RRs for neighbourhood studies were 3.8 (95% CI 0.4 to 38.4), 8.4 (95% CI 4.7 to 14.9) and 21.1 (95% CI 5.3 to 84.5) and meta-RRs for household studies were 4.0 (95% CI 0.8 to 18.8), 5.3 (95% CI 1.9 to 15.0) and 21.1 (95% CI 2.8 to 156.0).

CONCLUSIONS: PMM risks from non-occupational asbestos exposure are consistent with the fibre-type potency response observed in occupational settings. By relating our findings to knowledge of exposure-response relationships in occupational settings, we can better evaluate PMM risks in communities with ambient asbestos exposures from industrial or other sources.}, } @article {pmid28929108, year = {2017}, author = {Ju, L and Wu, W and Yu, M and Lou, J and Wu, H and Yin, X and Jia, Z and Xiao, Y and Zhu, L and Yang, J}, title = {Different Cellular Response of Human Mesothelial Cell MeT-5A to Short-Term and Long-Term Multiwalled Carbon Nanotubes Exposure.}, journal = {BioMed research international}, volume = {2017}, number = {}, pages = {2747215}, pmid = {28929108}, issn = {2314-6141}, mesh = {Asbestos/*toxicity ; Carcinogens ; Cell Line ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; DNA Damage/drug effects ; Humans ; Lung Neoplasms/*chemically induced ; Mesothelioma/*chemically induced ; Mesothelioma, Malignant ; Nanotubes, Carbon/*toxicity ; Time Factors ; }, abstract = {Despite being a commercially important product, multiwalled carbon nanotubes (MWCNTs) continue to raise concerns over human health due to their structural similarity to asbestos. Indeed, exposure to MWCNT has been shown to induce lung cancer and even mesothelioma, but contradictory results also exist. To clarify the potentially carcinogenic effects of rigid and rod-like MWCNT and to elucidate the underlying mechanisms, the effects of MWCNT on human mesothelial cell MeT-5A were examined throughout 3 months of continuous exposure, including cytotoxicity, genotoxicity, and cell motility. It was found that MWCNT did not affect MeT-5A cell proliferation at 10 μg/cm[2] within 72 h treatment, but under the same condition, MWCNT induced genotoxicity and perturbed cell motility. In addition, MeT-5A cells demonstrated different cellular responses to MWCNT after short-term and long-term exposure. Taken together, our results indicated a possible carcinogenic potential for MWCNT after long-term treatment, in which Annexin family proteins might be involved.}, } @article {pmid28925565, year = {2017}, author = {Egilman, D}, title = {Response to Hessel.}, journal = {American journal of industrial medicine}, volume = {60}, number = {10}, pages = {915-920}, doi = {10.1002/ajim.22773}, pmid = {28925565}, issn = {1097-0274}, mesh = {Asbestos/*toxicity ; Australia ; *Automobiles ; Humans ; Industry/*legislation & jurisprudence ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; Research Support as Topic/*ethics ; }, } @article {pmid28915695, year = {2017}, author = {Pouliquen, DL and Nawrocki-Raby, B and Nader, J and Blandin, S and Robard, M and Birembaut, P and Grégoire, M}, title = {Evaluation of intracavitary administration of curcumin for the treatment of sarcomatoid mesothelioma.}, journal = {Oncotarget}, volume = {8}, number = {34}, pages = {57552-57573}, pmid = {28915695}, issn = {1949-2553}, abstract = {A rat model of sarcomatoid mesothelioma, mimicking some of the worst clinical conditions encountered, was established to evaluate the therapeutic potential of intracavitary curcumin administration. The M5-T1 cell line, selected from a collection established from F344 rats induced with asbestos, produces tumors within three weeks, with extended metastasis in normal tissues, after intraperitoneal inoculation in syngeneic rats. The optimal concentration/time conditions for killing M5-T1 cells with curcumin were first determined in vitro. Secondly, the potential of intraperitoneal curcumin administration to kill tumor cells in vivo was evaluated in tumor-bearing rats, in comparison with a reference epigenetic drug, SAHA. Both agents administered at days 21 and 26 after tumor challenge produced necrosis within the solid tumors at day 28. However, tumor tissue necrosis induced with curcumin was much more extensive than with SAHA, and was characterized by infiltration with mononuclear phagocytic cells. In contrast, tumor tissue treated with SAHA contained foci of resistant cells and was infiltrated by many isolated CD8+ cells. The treatment of tumor-bearing rats with 1.5 mg/kg curcumin on days 7, 9, 11 and 14 after tumor challenge dramatically reduced the mean total tumor mass at day 16. Clusters of CD8+ T lymphocytes were observed at the periphery of small residual tumor masses in the peritoneal cavity, which presented a significant reduction in mitotic index, IL6 and vimentin expression compared with tumors in untreated rats. These data open up interesting new prospects for the therapy of sarcomatoid mesothelioma with curcumin and its derivatives.}, } @article {pmid28914691, year = {2017}, author = {Zadnik, V and Primic Zakelj, M and Jarm, K and Zagar, T}, title = {Time trends and spatial patterns in the mesothelioma incidence in Slovenia, 1961-2014.}, journal = {European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP)}, volume = {26 Joining forces for better cancer registration in Europe}, number = {}, pages = {S191-S196}, doi = {10.1097/CEJ.0000000000000384}, pmid = {28914691}, issn = {1473-5709}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Environmental Exposure/*adverse effects ; Female ; Humans ; Male ; Mesothelioma/diagnosis/*epidemiology ; Middle Aged ; Occupational Exposure/*adverse effects ; Registries/*statistics & numerical data ; Slovenia/epidemiology ; Time Factors ; }, abstract = {We aimed to explore the temporal and spatial variations in mesothelioma incidence in Slovenia for the last 50 years and, among these, to evaluate the consequences of asbestos usage. The incidence data from the population-based Cancer Registry of Republic of Slovenia for the period 1961-2014 were analysed. The data of asbestos imported to Slovenia were used as a proxy for asbestos exposure in manufacturing areas. Log-linear joinpoint regression and age-period-cohort Poisson models were used in the time-trend analysis. The mesothelioma maps were produced according to the method of local standardized incidence ratio estimates and are presented together with the map of Slovenian major asbestos-exposed locations. The maximum value of the asbestos import curve corresponds to the peak of mesothelioma curve exactly 30 years later. Both increases before the peak are comparable in time interval and steepness. The highest mesothelioma risk was detected for the cohort born between 1940 and 1944. In maps, the mesothelioma clusters manifest around known asbestos sources predominantly in the years 1980-1990, but in the last few years, the geographical distribution is more dispersed. The data from our long-existing population-based cancer registry provide a good insight into the on-going mesothelioma epidemic in Slovenia. Our results imply that the mesothelioma peak has already been reached in Slovenia. In the future, new cases will emerge more randomly throughout the country.}, } @article {pmid28913871, year = {2017}, author = {Greenberg, M}, title = {Experimental asbestos studies in the UK: 1912-1950.}, journal = {American journal of industrial medicine}, volume = {60}, number = {11}, pages = {956-962}, doi = {10.1002/ajim.22762}, pmid = {28913871}, issn = {1097-0274}, mesh = {Animals ; Asbestos/*history/toxicity ; Asbestosis/*history ; Biomedical Research/*history/methods ; Carcinogens/*history/toxicity ; Guinea Pigs ; History, 19th Century ; History, 20th Century ; Humans ; Lung Neoplasms/etiology/*history ; Mesothelioma/etiology/*history ; *Mining ; Occupational Exposure/adverse effects/*history ; Pulmonary Fibrosis/etiology/history ; Rats ; Schools, Medical/history ; United Kingdom ; }, abstract = {The asbestos industry originated in the UK in the 1870s. By 1898, asbestos had many applications and was reported to be one of the four leading causes of severe occupational disease. In 1912, the UK government sponsored an experimental study that reported that exposure to asbestos produced no more than a modicum of pulmonary fibrosis in guinea pigs. In the 1930s, the newly established Medical Research Council, with assistance from industry, sponsored a study of the effects of exposing animals to asbestos by injection (intratracheal and subcutaneous) and by inhalation in the factory environment. Government reports, publications, and contemporary records obtained by legal discovery have been reviewed in the context of the stage of scientific development and the history of the times. Experimenters were engaged in a learning process during the 1912-1950 period, and their reports of the effects of asbestos were inconsistent. Pathologists who studied the effects of asbestos experimentally, at whole animal, tissue and cellular levels, advanced experimental methodology and mechanistic knowledge. In the hands of public relations experts, however, research was exploited to preserve an industry and perpetuate preventable diseases, a practice that continues to this day.}, } @article {pmid28910456, year = {2018}, author = {Hung, YP and Dong, F and Watkins, JC and Nardi, V and Bueno, R and Dal Cin, P and Godleski, JJ and Crum, CP and Chirieac, LR}, title = {Identification of ALK Rearrangements in Malignant Peritoneal Mesothelioma.}, journal = {JAMA oncology}, volume = {4}, number = {2}, pages = {235-238}, pmid = {28910456}, issn = {2374-2445}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anaplastic Lymphoma Kinase/*genetics/metabolism ; DNA Mutational Analysis/methods ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Lung Neoplasms/*genetics/metabolism ; Male ; Mesothelioma/*genetics/metabolism ; Mesothelioma, Malignant ; Middle Aged ; *Mutation ; Oncogene Proteins, Fusion/genetics ; Peritoneal Neoplasms/*genetics/metabolism ; *Translocation, Genetic/genetics ; Young Adult ; }, abstract = {IMPORTANCE: Malignant peritoneal mesothelioma is a rare, aggressive tumor arising from the peritoneal lining, induced by asbestos, therapeutic radiation, or germline mutations. Nevertheless, the molecular features remain largely unknown.

OBJECTIVE: To investigate anaplastic lymphoma kinase (ALK) rearrangements in a large series of peritoneal mesothelioma and characterize the mutational landscape of these tumors.

We studied 88 consecutive patients (39 men, 49 women; median age 61, range 17-84 years) with peritoneal mesotheliomas diagnosed at a single institution between 2005 and 2015. We identified ALK-positive mesotheliomas by immunohistochemistry and confirmed ALK rearrangement by fluorescence in situ hybridization (FISH). In ALK-rearranged cases, we characterized the fusion partners using targeted next-generation sequencing of both tumor DNA and RNA. In select cases, we quantified asbestos fibers by combined scanning electron microscopy and x-ray spectroscopy. We also explored ALK rearrangement in a separate series of 205 patients with pleural mesothelioma.

MAIN OUTCOMES AND MEASURES: Identification and characterization of novel ALK rearrangements and correlations with clinicopathologic characteristics.

RESULTS: Anaplastic lymphoma kinase was positive by immunohistochemistry in 11 (13%) peritoneal mesotheliomas (focal weak in 8, diffuse strong in 3). In focal weak ALK-positive cases, no ALK rearrangement was detected by FISH or next-generation sequencing. In strong diffuse ALK-positive cases, FISH confirmed ALK rearrangements, and next-generation sequencing identified novel fusion partners ATG16L1, STRN, and TPM1. Patients with ALK-rearranged peritoneal mesotheliomas were women and younger than patients without ALK rearrangement (median age 36 vs 62; Mann-Whitney test, P = .02), but all other clinicopathologic characteristics (size of tumor nodules, histology, treatment, and survival) were not different. No asbestos fibers were detected in ALK-rearranged cases. Furthermore, loss of chromosomal region 9p or 22q or genetic alterations in BAP1, SETD2, or NF2 typically present in peritoneal mesothelioma were absent in the ALK-rearranged cases. All pleural mesotheliomas were ALK-negative by immunohistochemistry.

CONCLUSIONS AND RELEVANCE: We identified unique ALK rearrangements in a subset of patients with peritoneal mesothelioma, each lacking asbestos fibers, therapeutic radiation, and cytogenetic and molecular alterations typically found in these tumors. Identification of clinically actionable ALK rearrangements may represent a novel pathogenetic mechanism of malignant peritoneal mesothelioma with promise for targeted therapy.}, } @article {pmid28884745, year = {2018}, author = {Vivero, M and Bueno, R and Chirieac, LR}, title = {Clinicopathologic and genetic characteristics of young patients with pleural diffuse malignant mesothelioma.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {31}, number = {1}, pages = {122-131}, pmid = {28884745}, issn = {1530-0285}, support = {R01 CA120528/CA/NCI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Cyclin-Dependent Kinase Inhibitor p16 ; Cyclin-Dependent Kinase Inhibitor p18/genetics ; Female ; Humans ; Kaplan-Meier Estimate ; Lung Neoplasms/genetics/mortality/*pathology ; Male ; Mesothelioma/genetics/mortality/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/genetics/mortality/*pathology ; Proportional Hazards Models ; Young Adult ; }, abstract = {Pleural diffuse malignant mesothelioma typically presents during the seventh decade of life and has poor prognosis. Recent epidemiologic studies have shown differences between young and older mesothelioma patients, but the biology of pleural mesothelioma in young patients is poorly understood. We studied the clinicopathologic and genetic characteristics in pleural mesothelioma patients aged 35 years and younger. Thirty-six consecutive pleural mesothelioma patients aged 35 years and younger were compared with 48 older patients. We examined demographic and clinical characteristics, histologic type, growth patterns, mitotic index, and nuclear grade on hematoxylin and eosin-stained slides, BAP1 protein expression by immunohistochemistry, and CDKN2A and NF2 deletions by fluorescence in situ hybridization. Clinicopathologic and cytogenetic results were compared between young and older groups, and correlated with overall survival. Young patients were more frequently women, reported less asbestos exposure, and had a greater frequency of prior therapeutic radiation and family history of breast cancer than older patients (P<0.05 each). There were no histologic differences between young and older patients (all P>0.05). CDKN2A deletion was less prevalent in young patients (P=0.01), loss of BAP1 protein expression less frequent in young patients (P=0.06), and NF2 deletion rates similar between groups (P>0.05 each). Median overall survival was 40 vs 26 months (P=0.10) in young and older patients, respectively, and 47 vs 31 months (P=0.04) when comparing patients with epithelioid histology only. High mitotic index and non-epithelioid histology were the only characteristics associated with a poor overall survival in young patients. Young patients with pleural mesothelioma have an equal sex distribution and are more likely to have a history of mantle radiation, family history of breast cancer, and lower rates of CDKN2A deletion than older patients. Our results suggest that pleural mesothelioma in young patients has distinctive clinical and genetic characteristics, despite some similarities to pleural mesothelioma in older patients.}, } @article {pmid28881848, year = {2017}, author = {Lagniau, S and Lamote, K and van Meerbeeck, JP and Vermaelen, KY}, title = {Biomarkers for early diagnosis of malignant mesothelioma: Do we need another moonshot?.}, journal = {Oncotarget}, volume = {8}, number = {32}, pages = {53751-53762}, pmid = {28881848}, issn = {1949-2553}, abstract = {Early diagnosis of malignant pleural mesothelioma (MPM) is a challenge for clinicians. The disease is usually detected in an advanced stage which precludes curative treatment. We assume that only new and non-invasive biomarkers allowing earlier detection will result in better patient management and outcome. Many efforts have already been made to find suitable biomarkers in blood and pleural effusions, but have not yet resulted in a valid and reproducible diagnostic one. In this review, we will highlight the strengths and shortcomings of blood and fluid based biomarkers and highlight the potential of breath analysis as a non-invasive screening tool for MPM. This method seems very promising in the early detection of diverse malignancies, because exhaled breath contains valuable information on cell and tissue metabolism. Research that focuses on breath biomarkers in MPM is in its early days, but the few studies that have been performed show promising results. We believe a breathomics-based biomarker approach should be further explored to improve the follow-up and management of asbestos exposed individuals.}, } @article {pmid28870611, year = {2017}, author = {van Zandwijk, N and Pavlakis, N and Kao, SC and Linton, A and Boyer, MJ and Clarke, S and Huynh, Y and Chrzanowska, A and Fulham, MJ and Bailey, DL and Cooper, WA and Kritharides, L and Ridley, L and Pattison, ST and MacDiarmid, J and Brahmbhatt, H and Reid, G}, title = {Safety and activity of microRNA-loaded minicells in patients with recurrent malignant pleural mesothelioma: a first-in-man, phase 1, open-label, dose-escalation study.}, journal = {The Lancet. Oncology}, volume = {18}, number = {10}, pages = {1386-1396}, doi = {10.1016/S1470-2045(17)30621-6}, pmid = {28870611}, issn = {1474-5488}, mesh = {Adult ; Aged ; Australia ; Biopsy, Needle ; Cancer Care Facilities ; Disease-Free Survival ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Infusions, Intravenous ; Kaplan-Meier Estimate ; Lung Neoplasms/diagnostic imaging/*drug therapy/mortality/pathology ; Male ; Maximum Tolerated Dose ; Mesothelioma/diagnostic imaging/*drug therapy/mortality/pathology ; Mesothelioma, Malignant ; MicroRNAs/*administration & dosage ; Middle Aged ; Neoplasm Recurrence, Local/*drug therapy/mortality/pathology ; *Patient Safety ; Patient Selection ; Pleural Neoplasms/diagnostic imaging/*drug therapy/mortality/pathology ; Positron Emission Tomography Computed Tomography/methods ; Risk Assessment ; Survival Analysis ; Treatment Outcome ; }, abstract = {BACKGROUND: TargomiRs are minicells (EnGeneIC Dream Vectors) loaded with miR-16-based mimic microRNA (miRNA) and targeted to EGFR that are designed to counteract the loss of the miR-15 and miR-16 family miRNAs, which is associated with unsuppressed tumour growth in preclinical models of malignant pleural mesothelioma. We aimed to assess the safety, optimal dosing, and activity of TargomiRs in patients with malignant pleural mesothelioma.

METHODS: In this first-in-man, open-label, dose-escalation phase 1 trial at three major cancer centres in Sydney (NSW, Australia), we recruited adults (aged ≥18 years) with a confirmed diagnosis of malignant pleural mesothelioma, measurable disease, radiological signs of progression after previous chemotherapy, Eastern Cooperative Oncology Group performance status of 0 or 1, life expectancy of 3 months or more, immunohistochemical evidence of tumour EGFR expression, and adequate bone marrow, liver, and renal function. Patients were given TargomiRs via 20 min intravenous infusion either once or twice a week (3 days apart) in a traditional 3 + 3 dose-escalation design in five dose cohorts. The dose-escalation steps planned were 5 × 10[9], 7 × 10[9], and 9 × 10[9] TargomiRs either once or twice weekly, but after analysis of data from the first eight patients, all subsequent patients started protocol treatment at 1 × 10[9] TargomiRs. The primary endpoints were to establish the maximum tolerated dose of TargomiRs as measured by dose-limiting toxicity, define the optimal frequency of administration, and objective response (defined as the percentage of assessable patients with a complete or partial response), duration of response (defined as time from the first evidence of response to disease progression in patients who achieved a response), time to response (ie, time from start of treatment to the first evidence of response) and overall survival (defined as time from treatment allocation to death from any cause). Analyses were based on the full analysis set principle, including every patient who received at least one dose of TargomiRs. The study was closed for patient entry on Jan 3, 2017, and registered with ClinicalTrials.gov, number NCT02369198, and the Australian Registry of Clinical Trials, number ACTRN12614001248651.

FINDINGS: Between Sept 29, 2014, and Nov 24, 2016, we enrolled 27 patients, 26 of whom received at least one TargomiR dose (one patient died before beginning treatment). Overall, five dose-limiting toxicities were noted: infusion-related inflammatory symptoms and coronary ischaemia, respectively, in two patients given 5 × 10[9] TargomiRs twice weekly; anaphylaxis and cardiomyopathy, respectively, in two patients given 5 × 10[9] TargomiRs once weekly but who received reduced dexamethasone prophylaxis; and non-cardiac pain in one patient who received 5 × 10[9] TargomiRs once weekly. We established that 5 × 10[9] TargomiRs once weekly was the maximum tolerated dose. TargomiR infusions were accompanied by transient lymphopenia (25 [96%] of 26 patients), temporal hypophosphataemia (17 [65%] of 26 patients), increased aspartate aminotransferase or alanine aminotranferase (six [23%] of 26 patients), and increased alkaline phosphatase blood concentrations (two [8%]). Cardiac events occurred in five patients: three patients had electrocardiographic changes, one patient had ischaemia, and one patient had Takotsubo cardiomyopathy. Of the 22 patients who were assessed for response by CT, one (5%) had a partial response, 15 (68%) had stable disease, and six (27%) had progressive disease. The proportion of patients who achieved an objective response was therefore one (5%) of 22, and the duration of the objective response in that patient was 32 weeks. Median overall survival was 200 days (95% CI 94-358). During the trial, 21 deaths occurred, of which 20 were related to tumour progression and one was due to bowel perforation.

INTERPRETATION: The acceptable safety profile and early signs of activity of TargomiRs in patients with malignant pleural mesothelioma support additional studies of TargomiRs in combination with chemotherapy or immune checkpoint inhibitors.

FUNDING: Asbestos Diseases Research Foundation.}, } @article {pmid28866609, year = {2017}, author = {Odgerel, CO and Takahashi, K and Sorahan, T and Driscoll, T and Fitzmaurice, C and Yoko-O, M and Sawanyawisuth, K and Furuya, S and Tanaka, F and Horie, S and Zandwijk, NV and Takala, J}, title = {Estimation of the global burden of mesothelioma deaths from incomplete national mortality data.}, journal = {Occupational and environmental medicine}, volume = {74}, number = {12}, pages = {851-858}, pmid = {28866609}, issn = {1470-7926}, mesh = {Asbestos/*adverse effects ; Databases, Factual ; Environmental Exposure/*adverse effects ; Female ; *Global Health ; Humans ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; Mesothelioma, Malignant ; World Health Organization ; }, abstract = {BACKGROUND: Mesothelioma is increasingly recognised as a global health issue and the assessment of its global burden is warranted.

OBJECTIVES: To descriptively analyse national mortality data and to use reported and estimated data to calculate the global burden of mesothelioma deaths.

METHODS: For the study period of 1994 to 2014, we grouped 230 countries into 59 countries with quality mesothelioma mortality data suitable to be used for reference rates, 45 countries with poor quality data and 126 countries with no data, based on the availability of data in the WHO Mortality Database. To estimate global deaths, we extrapolated the gender-specific and age-specific mortality rates of the countries with quality data to all other countries.

RESULTS: The global numbers and rates of mesothelioma deaths have increased over time. The 59 countries with quality data recorded 15 011 mesothelioma deaths per year over the 3 most recent years with available data (equivalent to 9.9 deaths per million per year). From these reference data, we extrapolated the global mesothelioma deaths to be 38 400 per year, based on extrapolations for asbestos use.

CONCLUSIONS: Although the validity of our extrapolation method depends on the adequate identification of quality mesothelioma data and appropriate adjustment for other variables, our estimates can be updated, refined and verified because they are based on commonly accessible data and are derived using a straightforward algorithm. Our estimates are within the range of previously reported values but higher than the most recently reported values.}, } @article {pmid28863229, year = {2018}, author = {Glynn, ME and Keeton, KA and Gaffney, SH and Sahmel, J}, title = {Ambient Asbestos Fiber Concentrations and Long-Term Trends in Pleural Mesothelioma Incidence between Urban and Rural Areas in the United States (1973-2012).}, journal = {Risk analysis : an official publication of the Society for Risk Analysis}, volume = {38}, number = {3}, pages = {454-471}, doi = {10.1111/risa.12887}, pmid = {28863229}, issn = {1539-6924}, mesh = {Age Factors ; Asbestos/*adverse effects ; Female ; Humans ; Incidence ; Lung Neoplasms/*chemically induced/*epidemiology ; Male ; Mesothelioma/*chemically induced/*epidemiology ; Mesothelioma, Malignant ; Occupational Exposure/adverse effects ; Pleural Neoplasms/*chemically induced/*epidemiology ; Registries ; Rural Population ; SEER Program ; Sex Factors ; United States ; Urban Population ; }, abstract = {Over the past 40 years, measured ambient asbestos concentrations in the United States have been higher in urban versus rural areas. The purpose of this study was to determine whether variations in ambient asbestos concentrations have influenced pleural mesothelioma risk in females (who generally lacked historic occupational asbestos exposure relative to males). Male pleural mesothelioma incidence trends were analyzed to provide perspective for female trends. Annual age-adjusted incidence rates from 1973 to 2012 were obtained from the SEER 9, 13, and 18 databases for urban and rural locations, and standardized rate ratios were calculated. Female rural rates exceeded urban rates in almost half of the years analyzed, although the increases were not statistically significant, which is in line with expectations if there was no observable increased risk for urban locations. In contrast, male urban rates were elevated over rural rates for nearly all years examined and were statistically significantly elevated for 22 of the 40 years. Trend analyses demonstrated that trends for females remained relatively constant over time, whereas male urban and rural incidence increased into the 1980s and 1990s, followed by a decrease/leveling off. Annual female urban and rural incidence rates remained approximately five- to six-fold lower than male urban and rural incidence rates on average, consistent with the comparatively increased historical occupational asbestos exposure for males. The results suggest that differences in ambient asbestos concentrations, which have been reported to be 10-fold or greater across regions in the United States, have not influenced the risk of pleural mesothelioma.}, } @article {pmid28855951, year = {2017}, author = {Eisenhawer, C and Felten, MK and Hager, T and Gronostayskiy, M and Bruners, P and Tannapfel, A and Kraus, T}, title = {Migrating pleural plaque in a patient with asbestos induced pleural disease: a case report.}, journal = {Journal of occupational medicine and toxicology (London, England)}, volume = {12}, number = {}, pages = {25}, pmid = {28855951}, issn = {1745-6673}, abstract = {BACKGROUND: Health surveillance of formerly asbestos exposed individuals focus on early detection of asbestos related diseases, such as lung fibrosis (asbestosis), pleural plaques, mesothelioma and lung cancer in particular. One main concern is the early and clear identification of lesions with a high risk of malignant changes and their undelayed clinical work-up. False positive results may lead to unnecessary and often painful diagnostic interventions, which create high costs when applied to a large cohort and also may discredit the whole program. We describe an unusual presentation of a common lesion among asbestos exposed individuals, which has to our knowledge never been described before. Being aware of this pathological pathway may prevent inadequate clinical decisions with disadvantages for the patient. Underlying implications regarding health surveillance and the reading of CT-scans of the thorax are important for the management of formerly asbestos exposed individuals.

CASE PRESENTATION: During follow-up of an asbestos exposed 72 year old former power plant worker with known pleural changes, a nodule located next to the left costophrenic angle was newly discovered on CT-scan. As the previous scan 1 year before did not show any changes in that area, a fast growing tumour was suspected and an immediate biopsy performed. The tissue showed the characteristics of a pleural plaque with no signs of malignancy. After carefully reviewing all previous radiographs a rounded opacity attached to the mediastinal pleura close to the oesophagus and slightly cranial to the position of the removed nodule could be discerned. That nodule had increased in size over several years and was no longer visible on the latest scan. It appeared that the originally slow growing plaque had migrated to the costophrenic angle some time before it was discovered in the latest scan thus imposing as a fast growing tumour.

CONCLUSIONS: We concluded that asbestos related pleural plaques can under special circumstances get separated from the pleura and migrate to another position in the pleural cavity. The case provides new insights in the development and properties of pleural lesions and may offer new options for the management of formerly asbestos exposed patients.}, } @article {pmid28852644, year = {2017}, author = {Ndlovu, N and Rees, D and Murray, J and Vorajee, N and Richards, G and teWaterNaude, J}, title = {Asbestos-related diseases in mineworkers: a clinicopathological study.}, journal = {ERJ open research}, volume = {3}, number = {3}, pages = {}, pmid = {28852644}, issn = {2312-0541}, support = {D43 ES018744/ES/NIEHS NIH HHS/United States ; }, abstract = {The accurate diagnosis of asbestos-related diseases is important because of past and current asbestos exposures. This study evaluated the reliability of clinical diagnoses of asbestos-related diseases in former mineworkers using autopsies as the reference standard. Sensitivity, specificity, positive predictive value and negative predictive value were calculated. The 149 cases identified had clinical examinations 0.3-7.4 years before death. More asbestos-related diseases were diagnosed at autopsy rather than clinically: 77 versus 52 for asbestosis, 27 versus 14 for mesothelioma and 22 versus 3 for lung cancer. Sensitivity and specificity values for clinical diagnoses were 50.6% and 81.9% for asbestosis, 40.7% and 97.5% for mesothelioma, and 13.6% and 100.0% for lung cancer. False-negative diagnoses of asbestosis were more likely using radiographs of acceptable (versus good) quality and in cases with pulmonary tuberculosis at autopsy. The low sensitivity values are indicative of the high proportion of false-negative diagnoses. It is unlikely that these were the result of disease manifestation between the last clinical assessment and autopsy. Where clinical features suggest asbestos-related diseases but the chest radiograph is negative, more sophisticated imaging techniques or immunohistochemistry for asbestos-related cancers should be used. Autopsies are useful for the detection of previously undiagnosed and misdiagnosed asbestos-related diseases, and for monitoring clinical practice and delivery of compensation.}, } @article {pmid28845826, year = {2017}, author = {Cardinale, L and Ardissone, F and Gned, D and Sverzellati, N and Piacibello, E and Veltri, A}, title = {Diagnostic Imaging and workup of Malignant Pleural Mesothelioma.}, journal = {Acta bio-medica : Atenei Parmensis}, volume = {88}, number = {2}, pages = {134-142}, pmid = {28845826}, issn = {2531-6745}, mesh = {Humans ; Lung Neoplasms/*diagnostic imaging ; Magnetic Resonance Imaging ; Mesothelioma/*diagnostic imaging ; Mesothelioma, Malignant ; Pleural Neoplasms/*diagnostic imaging ; Positron Emission Tomography Computed Tomography ; Radiography, Thoracic ; Tomography, X-Ray Computed ; Ultrasonography ; }, abstract = {Malignant pleural mesothelioma is the most frequent primary neoplasm of the pleura and its incidence is still increasing.This tumor has a strong association with exposure to occupational or environmental asbestos, often after a long latent period of 30-40 years.Plain chest radiography (CXR) is usually the first-line radiologic examination, but the radiographic findings are nonspecific due to its limited contrast resolution and they need to be complemented by other imaging modalities such as computed tomography (CT), magnetic resonance Imaging (MRI), Positron emission tomography-computed tomography (PET-CT) and ultrasound (US).The aim of this paper is to describe the imaging features of this malignancy, underlining the peculiarity of CXR, CT, MRI, PET-CT and US and also focusing on diagnostic workup, based on the literature evidence and according to our experience.}, } @article {pmid28838403, year = {2017}, author = {Lau, B and Kumar, S and Yan, T and Burn, J and Kennedy, C and McLean, J and Boyer, M and McCaughan, B and Kao, S}, title = {Pathological complete response in malignant pleural mesothelioma patients following induction chemotherapy: Predictive factors and outcomes.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {111}, number = {}, pages = {75-78}, doi = {10.1016/j.lungcan.2017.07.010}, pmid = {28838403}, issn = {1872-8332}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use ; Combined Modality Therapy ; Female ; Humans ; Induction Chemotherapy ; Kaplan-Meier Estimate ; Lung Neoplasms/*drug therapy/mortality/*pathology ; Male ; Mesothelioma/*drug therapy/mortality/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Neoplasm Staging ; Pleural Neoplasms/*drug therapy/mortality/*pathology ; Prognosis ; Retrospective Studies ; Treatment Outcome ; }, abstract = {A small proportion of patients with malignant pleural mesothelioma (MPM) achieve pathological complete response (CR) following treatment with current practice induction chemotherapy. Our analysis of 58 patients with MPM treated with platinum-based chemotherapy showed 4 patients (7%) attained pathological CR at subsequent extrapleural pneumonectomy (EPP). Patient and tumour factors such as age, gender, smoking habit, histological subtype, and clinical stage were not found to be associated with pathological CR. Patients with pathological CR had longer disease-free survival (29.2 vs. 13.8 months; p=0.08) and overall survival (76.4 vs. 23.4 months; p=0.06) but this did not reach statistical significance. Our study suggests that patients who achieve pathological CR after chemotherapy may have improved survival in MPM.}, } @article {pmid28838385, year = {2017}, author = {Scarlata, S and Finamore, P and Giannunzio, G and Santangelo, S and Antonelli Incalzi, R}, title = {Chest ultrasonography in health surveillance of asbestos related pleural disease.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {111}, number = {}, pages = {139-142}, doi = {10.1016/j.lungcan.2017.07.019}, pmid = {28838385}, issn = {1872-8332}, mesh = {Adult ; Asbestos/*adverse effects ; Carcinogens ; Female ; Humans ; Male ; Mass Screening ; Middle Aged ; Occupational Exposure/*adverse effects ; Pleural Diseases/*diagnosis/epidemiology/*etiology ; *Public Health Surveillance ; Time Factors ; Tomography, X-Ray Computed ; *Ultrasonography ; }, abstract = {High resolution computed tomography, (HRCT), is currently considered the diagnostic gold standard to diagnose early stage malignant pleural mesothelioma and other non-malignant pleural conditions, but it is expensive and exposes the patient to radiation dose. In a screening and population medicine perspective, Thoracic Ultrasounds may become a valuable alternative because it can detect minimal changes in pleural surface, is widely available and safe. On these bases, we therefore validated thoracic US in subjects with history of exposure to asbestos, having HRCT as the reference standard. One hundred-fifty subjects were screened and 117 were recruited. Pleural abnormalities at US and/or HRCT were detected in 66 out of 117 subjects (prevalence=57%), and their prevalence was unrelated to both mansion and smoking habit, while mean age and mean length of exposure were higher in those having pleural abnormalities (age=47±5 vs 44±6years, p<0.05;years of exposure=20±7 vs 17±5, p<0.05). Thirteen out of 19 subjects with pleural abnormalities at HRCT were also identified by thoracic US, whereas 47 participants had lesions seen at US, but not at the HRCT scan. Positive and negative percent agreement were 66.6% and 51.8%, respectively; the McNemar's test for equality showed a p-value <0.001. In conclusion, chest US might complement HRCT in the health surveillance of asbestos exposed population to detect earlier lesions or to follow up US approachable lesions. Further research is needed to clarify whether this approach may enhance early recognition of pleural mesothelioma and ameliorate prognosis.}, } @article {pmid28833303, year = {2017}, author = {Oddone, E and Ferrante, D and Tunesi, S and Magnani, C}, title = {Mortality in asbestos cement workers in Pavia, Italy: A cohort study.}, journal = {American journal of industrial medicine}, volume = {60}, number = {10}, pages = {852-866}, doi = {10.1002/ajim.22750}, pmid = {28833303}, issn = {1097-0274}, mesh = {Adult ; Asbestos/adverse effects ; Asbestosis/*mortality ; Cohort Studies ; Construction Industry/*statistics & numerical data ; Construction Materials ; Female ; Humans ; Italy/epidemiology ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; Mesothelioma, Malignant ; Middle Aged ; Occupational Diseases/etiology/*mortality ; Occupational Exposure ; Peritoneal Neoplasms/mortality ; Pleural Neoplasms/mortality ; }, abstract = {BACKGROUND: The aim of this study was to describe the mortality of a cohort of asbestos-cement workers in the largest plant in the most industrialized Italian region (Lombardy).

METHODS: A cohort study was carried out on 1818 subjects, corresponding to 47 536.1 person-years of observation. Standardized mortality ratios (SMRs) were computed for the major causes of death.

RESULTS: Increased SMRs were observed for pleural, peritoneal and lung cancers, and for asbestosis (SMR 26.73, 95% Confidence Interval (CI) 20.99-33.55; 9.15, 95%CI 5.00-15.34; 1.48, 95%CI 1.27-1.72; and 368.05, 95%CI 214.40-589.29, respectively). No excess in mortality for laryngeal cancer was observed (SMR 0.70, 95%CI 0.30-1.39). An increased mortality for ovarian cancer (SMR 3.64, 95%CI 0.99-9.33) was observed, although it was not statistically significant. Among men, mortality for pleural malignant mesothelioma was observed to be related to the duration of exposure, though not to latency.

CONCLUSIONS: The results of this study are generally consistent with present knowledge. Conversely, our results do not support the hypothesis that pleural malignant mesothelioma risk indefinitely increases after exposure, suggesting instead that the alternative hypothesis of a risk plateau or decrease after a time since first exposure of more than 40 years is more consistent with the observed data.}, } @article {pmid28829357, year = {2017}, author = {Serio, G and Pezzuto, F and Marzullo, A and Scattone, A and Cavone, D and Punzi, A and Fortarezza, F and Gentile, M and Buonadonna, AL and Barbareschi, M and Vimercati, L}, title = {Peritoneal Mesothelioma with Residential Asbestos Exposure. Report of a Case with Long Survival (Seventeen Years) Analyzed by Cgh-Array.}, journal = {International journal of molecular sciences}, volume = {18}, number = {8}, pages = {}, pmid = {28829357}, issn = {1422-0067}, mesh = {Adult ; Asbestos/*adverse effects ; Biopsy ; Comparative Genomic Hybridization ; *Environmental Exposure ; Humans ; Immunohistochemistry ; Lung Neoplasms/*diagnosis/*etiology ; Male ; Mesothelioma/*diagnosis/*etiology ; Mesothelioma, Malignant ; Peritoneal Neoplasms/*diagnosis/*etiology ; }, abstract = {UNLABELLED: Malignant mesothelioma is a rare and aggressive tumor with limited therapeutic options. We report a case of a malignant peritoneal mesothelioma (MPM) epithelioid type, with environmental asbestos exposure, in a 36-year-old man, with a long survival (17 years). The patient received standard treatment which included cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).

METHODS AND RESULTS: Molecular analysis with comparative genomic hybridization (CGH)-array was performed on paraffin-embedded tumoral samples. Multiple chromosomal imbalances were detected. The gains were prevalent. Losses at 1q21, 2q11.1→q13, 8p23.1, 9p12→p11, 9q21.33→q33.1, 9q12→q21.33, and 17p12→p11.2 are observed. Chromosome band 3p21 (BAP1), 9p21 (CDKN2A) and 22q12 (NF2) are not affected. Conclusions: the defects observed in this case are uncommon in malignant peritoneal mesothelioma. Some chromosomal aberrations that appear to be random here, might actually be relevant events explaining the response to therapy, the long survival and, finally, may be considered useful prognostic factors in peritoneal malignant mesothelioma (PMM).}, } @article {pmid28827980, year = {2017}, author = {Khmou, M and Echcharif, S and Kabbaj, R and Khannoussi, BE}, title = {Malignant Deciduoid Mesothelioma: case presentation of an exceptional variant and review of the literature.}, journal = {BMC clinical pathology}, volume = {17}, number = {}, pages = {13}, pmid = {28827980}, issn = {1472-6890}, abstract = {BACKGROUND: Malignant Deciduoid Mesothelioma (MDM) is an extremely rare variant of epithelioid mesothelioma. It was first described in young females, in the peritoneum, and its relation with asbestos was not well defined. Later reports, have shown that this variant may also occur in the pleura, the pericardium and the tunica vaginalis of elderly people, who had been exposed to asbestos.

CASE PRESENTATION: We report a case of malignant deciduoid mesothelioma that occurred in the peritoneal cavity, and the omentum of a 35-year-old woman. The patient had never been exposed to asbestos.

CONCLUSIONS: Through this observation, we describe clinical, histopathological, and immunohistochemical findings of deciduoid mesothelioma, and review the literature reports.}, } @article {pmid28823988, year = {2018}, author = {Boffetta, P and Pira, E and Romano, C and Violante, FS and Farioli, A and Zocchetti, C and La Vecchia, C}, title = {Response to: 'Dose-time-response association between occupational asbestos exposure and pleural mesothelioma' by Lacourt et al.}, journal = {Occupational and environmental medicine}, volume = {75}, number = {2}, pages = {160}, doi = {10.1136/oemed-2017-104570}, pmid = {28823988}, issn = {1470-7926}, mesh = {*Asbestos ; Humans ; *Lung Neoplasms ; *Mesothelioma ; *Pleural Neoplasms ; }, } @article {pmid28823918, year = {2017}, author = {Hattori, K and Nakadate, K and Morii, A and Noguchi, T and Ogasawara, Y and Ishii, K}, title = {Exposure to nano-size titanium dioxide causes oxidative damages in human mesothelial cells: The crystal form rather than size of particle contributes to cytotoxicity.}, journal = {Biochemical and biophysical research communications}, volume = {492}, number = {2}, pages = {218-223}, doi = {10.1016/j.bbrc.2017.08.054}, pmid = {28823918}, issn = {1090-2104}, mesh = {Cell Line ; Crystallization ; DNA Damage/*drug effects ; Epithelial Cells/cytology/*drug effects/metabolism/pathology ; Humans ; Nanostructures/*toxicity ; Oxidative Stress/*drug effects ; Particle Size ; Pleura/cytology/drug effects/metabolism/pathology ; Reactive Oxygen Species/metabolism ; Titanium/*toxicity ; }, abstract = {Exposure to nanoparticles such as carbon nanotubes has been shown to cause pleural mesothelioma similar to that caused by asbestos, and has become an environmental health issue. Not only is the percutaneous absorption of nano-size titanium dioxide particles frequently considered problematic, but the possibility of absorption into the body through the pulmonary route is also a concern. Nevertheless, there are few reports of nano-size titanium dioxide particles on respiratory organ exposure and dynamics or on the mechanism of toxicity. In this study, we focused on the morphology as well as the size of titanium dioxide particles. In comparing the effects between nano-size anatase and rutile titanium dioxide on human-derived pleural mesothelial cells, the anatase form was shown to be actively absorbed into cells, producing reactive oxygen species and causing oxidative damage to DNA. In contrast, we showed for the first time that the rutile form is not easily absorbed by cells and, therefore, does not cause oxidative DNA damage and is significantly less damaging to cells. These results suggest that with respect to the toxicity of titanium dioxide particles on human-derived mesothelial cells, the crystal form rather than the particle size has a greater effect on cellular absorption. Also, it was indicated that the difference in absorption is the primary cause of the difference in the toxicity against mesothelial cells.}, } @article {pmid28817672, year = {2017}, author = {Kwak, KM and Paek, D and Hwang, SS and Ju, YS}, title = {Estimated future incidence of malignant mesothelioma in South Korea: Projection from 2014 to 2033.}, journal = {PloS one}, volume = {12}, number = {8}, pages = {e0183404}, pmid = {28817672}, issn = {1932-6203}, mesh = {History, 21st Century ; Humans ; Incidence ; Lung Neoplasms/*epidemiology ; Mesothelioma/*epidemiology ; Mesothelioma, Malignant ; Registries ; Republic of Korea/epidemiology ; }, abstract = {Malignant mesothelioma is a malignant tumor on the pleura or the peritoneum caused mostly by asbestos. Although asbestos is not currently used in South Korea, the incidence of mesothelioma is increasing due to its long latent period. This study predicted the incidence of malignant mesothelioma in South Korea over the next 20 years using an age-period-cohort (APC) model. Data regarding mesothelioma incidence from 1994-2013 were acquired from the Korea Central Cancer Registry (KCCR). Demographic data, including prospective resident data, were acquired from the Korean Statistical Information Service (KOSIS) for 1994-2033. An APC model with Møller's power-link function was utilized to predict the incidence of mesothelioma. It was predicted that 2,380 and 1,199 new cases of mesothelioma in men and women, respectively, would occur over the next 20 years. For both sexes, the mesothelioma incidence rate was predicted to be greater in 2029-2033 compared to that in 2009-2013 (men, 0.282 vs 0.563; women, 0.155 vs 0.217). For men, the age-standardized incidence rate was predicted to be slightly greater in 2029-2033 relative to the rate in 2009-2013 (0.228 vs 0.235), while the age-standardized incidence rate in women decreased within the same timeframe (0.113 vs 0.109). The changes in mesothelioma incidence were mostly caused by changes in the population structure due to aging and not by changes in the mesothelioma risk ratio. The results of this study project a continuous increase in mesothelioma incidence in South Korea over the next 20 years. Although the projected increase in mesothelioma incidence was not related to an increase in the mesothelioma risk ratio, continuous preventive efforts are necessary to reduce the exposure to asbestos and prevent the trend from worsening.}, } @article {pmid28810297, year = {2017}, author = {Wei, MC and Yang, SJ}, title = {[Clinical and pathologic features of extrapleural sarcomatoid mesothelioma].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {46}, number = {8}, pages = {559-564}, doi = {10.3760/cma.j.issn.0529-5807.2017.08.008}, pmid = {28810297}, issn = {0529-5807}, mesh = {Adult ; Aged ; Biomarkers, Tumor/analysis ; Bone Neoplasms/chemistry/*pathology ; Calbindin 2/analysis ; Diagnosis, Differential ; Female ; Fibrosarcoma/pathology ; Head and Neck Neoplasms/chemistry/*pathology ; Humans ; Immunohistochemistry ; Keratins/analysis ; Male ; Mesothelioma/chemistry/diagnosis/*pathology ; Middle Aged ; Neoplasm Recurrence, Local ; Peritoneal Neoplasms/chemistry/*pathology ; Prognosis ; Sarcoma/pathology ; Vimentin/analysis ; }, abstract = {Objective: To investigate the morphological features, diagnosis and differential diagnosis of extrapleural sarcomatoid malignant mesothelioma (SMM). Methods: Six cases of extrapleural SMM were evaluated for their clinical, histological, immunohistochemical features, and prognosis. Results: Patients included 3 men and 3 women, with a median age of 60 years (range 41-75 years). All patients had no asbestos exposure in history and no pleural lesions. The tumors involved peritoneum (3 cases), bone (2 cases), and neck soft tissue (1 case). Histologically, the tumors were mainly composed of slender to plump spindle cells with occasional polymorphic cells, arranged in fascicular to storiform pattern or haphazardly organized, closely resembling those of fibromatosis, fibrosarcoma or malignant fibrous histiocytoma. The tumor cells were imunohistochemically positive for cytokeratin (pan, 6/6), calretinin (5/6), podoplanin (6/6), D2-40 (4/6), vimentin (6/6), WT1 (4/6), CD10 (3/6), SMA (4/6), and variably positive for CK7, and CK8/18, but were negative for other linage-specific markers. The Ki-67 proliferation indexes ranged from 25% to 55%, consistent with the diagnosis of malignant mesothelioma of the sarcomatous type. Ultrastructurally, the tumor cells possessed discontinuous external lamina, cytoplasmic processes, microfilaments and desmosomal intercellular junctions. Local recurrence or metastasis was seen in 1 case and 4 cases, respectively, after surgery, and all the patients died of the disease within 9 months. Conclusions: Extrapleural SMM, although rare, should be considered as a differential diagnosis among other benign or malignant sarcomatoid tumors and sarcomas. Along with clinical and radiological presentation, the combination of broad-spectrum cytokeratin, vimentin, and a series of mesothelial markers are useful for diagnosis of SMM.}, } @article {pmid28791466, year = {2017}, author = {Velasco-García, MI and Cruz, MJ and Diego, C and Montero, MA and Álvarez-Simón, D and Ferrer, J}, title = {First Identification of Pulmonary Asbestos Fibres in a Spanish Population.}, journal = {Lung}, volume = {195}, number = {5}, pages = {671-677}, pmid = {28791466}, issn = {1432-1750}, support = {Fis PI07/90478//Instituto de Salud Carlos III/ ; CP12/03101//Instituto de Salud Carlos III/ ; }, mesh = {Aged ; Aged, 80 and over ; *Asbestos, Amphibole ; Asbestosis/*pathology ; Case-Control Studies ; Female ; Humans ; *Lung ; Lung Neoplasms/*pathology/surgery ; Male ; Mesothelioma/*pathology ; Microscopy, Electron ; Microscopy, Electron, Scanning ; Middle Aged ; Mineral Fibers ; *Occupational Exposure ; Pleural Neoplasms/*pathology ; Spain ; Spectrometry, X-Ray Emission ; }, abstract = {INTRODUCTION: This study aimed to characterize, for the first time in Spain, the type of asbestos fibres (AF) in the lungs of exposed and non-exposed populations.

MATERIALS AND METHODS: Lung samples from 38 subjects living in Barcelona and Ferrol, Spain, were studied, which were divided into three groups: Group A-five subjects without known respiratory disease; Group B-20 ex-shipyard workers and Group C-13 patients with lung cancer. After eliminating the organic material, the inorganic residue was analysed using electronic microscopy (EM). To identify the type of fibre, the samples were analysed by scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX).

RESULTS: All the fibres identified corresponded to amphiboles (crocidolite 45%, anthophyllite 22%, tremolite 16%, amosite 15% and actinolite 3%). In 14 patients (37%), a single type of asbestos was found in the lungs (amosite in two, actinolite in one, anthophyllite in four, crocidolite in five and tremolite in two). Forty-six percent of the AF analysed had a length > 5 µm and a diameter < 0.2 µm.

CONCLUSIONS: The results of this study provide the first data on the type of asbestos retained in the lung of Spanish population. A particularly striking finding is the exclusive retention of amphiboles, which suggests that chrysotile is eliminated after inhalation. Our findings support estimations considering Spain and other southern European countries with similar asbestos imports and consumption at a high risk to develop asbestos-related diseases in the years to come.}, } @article {pmid28791219, year = {2017}, author = {Shaikh, AA and Naik, KV and Shetty, SN and Ansari, NN and Babhale, PS}, title = {Bilateral Malignant Mesothelioma of Tunica Vaginalis A Case Report on Rare Presentation.}, journal = {Urology case reports}, volume = {14}, number = {}, pages = {53-55}, pmid = {28791219}, issn = {2214-4420}, abstract = {Malignant mesothelioma involving the para-testicular tunica is extremely rare and an aggressive tumor. Bilateral malignant mesothelioma of the tunica vaginalis is not reported previously in the literature. Rarity of the disease, absence of any specific clinical and radiological findings makes the preoperative diagnosis difficult. Aggressive surgical approach is the key to successful management with high inguinal orchiectomy and scrotectomy appears to be optimal treatment in patients with localized disease.}, } @article {pmid28777435, year = {2018}, author = {Muscella, A and Cossa, LG and Vetrugno, C and Antonaci, G and Marsigliante, S}, title = {Inhibition of ZL55 cell proliferation by ADP via PKC-dependent signalling pathway.}, journal = {Journal of cellular physiology}, volume = {233}, number = {3}, pages = {2526-2536}, doi = {10.1002/jcp.26128}, pmid = {28777435}, issn = {1097-4652}, mesh = {Adenosine Diphosphate/analogs & derivatives/*pharmacology ; Antineoplastic Agents/*pharmacology ; Asbestos/adverse effects ; Cell Cycle Proteins/metabolism ; Cell Line, Tumor ; Cell Proliferation/*drug effects ; Dose-Response Relationship, Drug ; Enzyme Activation ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Humans ; JNK Mitogen-Activated Protein Kinases/metabolism ; Mesothelioma/*drug therapy/enzymology/genetics/pathology ; Phosphorylation ; Protein Kinase C-alpha/genetics/*metabolism ; Protein Kinase C-delta/genetics/*metabolism ; Protein Stability ; Purinergic P2Y Receptor Agonists/*pharmacology ; RNA Interference ; Receptors, Purinergic P2Y1/*drug effects/metabolism ; Signal Transduction/*drug effects ; Thionucleotides/pharmacology ; Time Factors ; Transfection ; Tumor Suppressor Protein p53/genetics/metabolism ; }, abstract = {Extracellular nucleotides can regulate cell proliferation in both normal and tumorigenic tissues. Here, we studied how extracellular nucleotides regulate the proliferation of ZL55 cells, a mesothelioma-derived cell line obtained from bioptic samples of asbestos-exposed patients. ADP and 2-MeS-ADP inhibited ZL55 cell proliferation, whereas ATP, UTP, and UDP were inactive. The nucleotide potency profile and the blockade of the ADP-mediated inhibitory effect by the phospholipase C inhibitor U-73122 suggest that P2Y1 receptor controls ZL55 cell proliferation. The activation of P2Y1 receptor by ADP leads to activation of intracellular transduction pathways involving [Ca[2+] ]i , PKC-δ/PKC-α, and MAPKs, ERK1/2 and JNK1/2. Cell treatment with ADP or 2-MeS-ADP also provokes the activation of p53, causing an accumulation of the G1 cyclin-dependent kinase inhibitors p21[WAF1] and p27[Kip] . Inhibition of ZL55 cell proliferation by ADP was completely reversed by inhibiting MEK1/2, or JNK1/2, or PKC-δ, and PKC-α. Through the inhibition of ADP-activated transductional kinases it was found that PKC-δ was responsible for JNK1/2 activation. JNK1/2 has a role in transcriptional up-regulation of p53, p21[WAF1/CIP1] , and p27[kip1] . Conversely, the ADP-activated PKC-α provoked ERK1/2 phosphorylation. ERK1/2 increased p53 stabilization, required to G1 arrest of ZL55 cells. Concluding, the importance of the study is twofold: first, results shed light on the mechanism of cell cycle inhibition by ADP; second, results suggest that extracellular ADP may inhibit mesothelioma progression.}, } @article {pmid28775133, year = {2017}, author = {Ferrante, D and Chellini, E and Merler, E and Pavone, V and Silvestri, S and Miligi, L and Gorini, G and Bressan, V and Girardi, P and Ancona, L and Romeo, E and Luberto, F and Sala, O and Scarnato, C and Menegozzo, S and Oddone, E and Tunesi, S and Perticaroli, P and Pettinari, A and Cuccaro, F and Mattioli, S and Baldassarre, A and Barone-Adesi, F and Cena, T and Legittimo, P and Marinaccio, A and Mirabelli, D and Musti, M and Pirastu, R and Ranucci, A and Magnani, C and , }, title = {Italian pool of asbestos workers cohorts: mortality trends of asbestos-related neoplasms after long time since first exposure.}, journal = {Occupational and environmental medicine}, volume = {74}, number = {12}, pages = {887-898}, doi = {10.1136/oemed-2016-104100}, pmid = {28775133}, issn = {1470-7926}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Asbestosis/mortality ; Carcinogens ; Cause of Death/trends ; Cohort Studies ; Construction Materials ; Female ; Humans ; Italy/epidemiology ; Lung ; Lung Neoplasms/etiology/*mortality ; Male ; Mesothelioma/etiology/*mortality ; Mesothelioma, Malignant ; Middle Aged ; Occupational Diseases/etiology/*mortality ; Occupational Exposure/*adverse effects ; Ovarian Neoplasms/etiology/*mortality ; Ovary ; Peritoneal Neoplasms/etiology/*mortality ; Peritoneum ; Pleura ; Pleural Neoplasms/etiology/*mortality ; }, abstract = {OBJECTIVE: Asbestos is a known human carcinogen, with evidence for malignant mesothelioma (MM), cancers of lung, ovary, larynx and possibly other organs. MM rates are predicted to increase with a power of time since first exposure (TSFE), but the possible long-term attenuation of the trend is debated. The asbestos ban enforced in Italy in 1992 gives an opportunity to measure long-term cancer risk in formerly exposed workers.

METHODS: Pool of 43 previously studied Italian asbestos cohorts (asbestos cement, rolling stock, shipbuilding), with mortality follow-up updated to 2010. SMRs were computed for the 1970â€"2010 period, for the major causes, with consideration of duration and TSFE, using reference rates by age, sex, region and calendar period.

RESULTS: The study included 51 801 subjects (5741 women): 55.9% alive, 42.6% died (cause known for 95%) and 1.5% lost to follow-up. Mortality was significantly increased for all deaths (SMR: men: 1.05, 95% CI 1.03 to 1.06; women: 1.17, 95% CI to 1.12 to 1.22), all malignancies combined (SMR: men: 1.17, 95% CI to 1.14 to 1.20; women: 1.33, 95% CI 1.24 to 1.43), pleural and peritoneal malignancies (SMR: men: 13.28 and 4.77, 95% CI 12.24 to 14.37 and 4.00 to 5.64; women: 28.44 and 6.75, 95% CI 23.83 to 33.69 and 4.70 to 9.39), lung (SMR: men: 1.26, 95% CI 1.21 to 1.31; women: 1.43, 95% CI 1.13 to 1.78) and ovarian cancer (SMR=1.38, 95% CI 1.00 to 1.87) and asbestosis (SMR: men: 300.7, 95% CI 270.7 to 333.2; women: 389.6, 95% CI 290.1 to 512.3). Pleural cancer rate increased during the first 40 years of TSFE and reached a plateau after.

DISCUSSION: The study confirmed the increased risk for cancer of the lung, ovary, pleura and peritoneum but not of the larynx and the digestive tract. Pleural cancer mortality reached a plateau at long TSFE, coherently with recent reports.}, } @article {pmid28757678, year = {2017}, author = {Mozzoni, P and Ampollini, L and Goldoni, M and Alinovi, R and Tiseo, M and Gnetti, L and Carbognani, P and Rusca, M and Mutti, A and Percesepe, A and Corradi, M}, title = {MicroRNA Expression in Malignant Pleural Mesothelioma and Asbestosis: A Pilot Study.}, journal = {Disease markers}, volume = {2017}, number = {}, pages = {9645940}, pmid = {28757678}, issn = {1875-8630}, mesh = {Aged ; Asbestosis/*blood/metabolism/pathology ; Case-Control Studies ; Female ; Humans ; Lung/metabolism ; Lung Neoplasms/*blood/metabolism/pathology ; Male ; Mesothelioma/*blood/metabolism/pathology ; Mesothelioma, Malignant ; MicroRNAs/*blood/genetics/metabolism ; Middle Aged ; Pilot Projects ; }, abstract = {BACKGROUND: The identification of diagnostic/prognostic biomarkers for asbestos-related diseases is relevant for early diagnosis and patient survival and may contribute to understanding the molecular mechanisms underlying the disease development and progression.

AIMS: To identify a pattern of miRNAs as possible diagnostic biomarkers for patients with malignant pleural mesothelioma (MPM) and asbestosis (ASB) and as prognostic biomarkers for MPM patients.

METHODS: miRNA-16, miRNA-17, miRNA-126, and miRNA-486 were quantified in plasma and formalin-fixed paraffin-embedded samples to evaluate their diagnostic and prognostic roles compared to patients with other noncancerous pulmonary diseases (controls). Results. The expression of all the miRNAs was significantly lower in patients with MPM and ASB than that in controls. miRNA-16, miRNA-17, and miRNA-486 in plasma and tissue of MPM patients were significantly correlated. Furthermore, the expression of miRNA-16 in plasma and tissue, and miRNA-486 only in tissue, was positively related with cumulative survival in MPM patients.

CONCLUSIONS: All the miRNA levels were decreased in patients with MPM or ASB, supporting the role of circulating miRNAs as a potential tool for diseases associated with exposure to asbestos fibers. miRNA-16 was directly related to MPM patient prognosis, suggesting its possible use as a prognostic marker in MPM patients.}, } @article {pmid28756416, year = {2017}, author = {Tompa, E and Kalcevich, C and McLeod, C and Lebeau, M and Song, C and McLeod, K and Kim, J and Demers, PA}, title = {The economic burden of lung cancer and mesothelioma due to occupational and para-occupational asbestos exposure.}, journal = {Occupational and environmental medicine}, volume = {74}, number = {11}, pages = {816-822}, pmid = {28756416}, issn = {1470-7926}, mesh = {Aged ; Asbestos/*adverse effects ; *Cost of Illness ; Female ; Health Care Costs ; Humans ; Lung/drug effects ; Lung Neoplasms/chemically induced/*economics ; Male ; Mesothelioma/chemically induced/*economics ; Middle Aged ; Occupational Diseases/chemically induced/*economics ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/chemically induced/*economics ; Quality of Life ; Quality-Adjusted Life Years ; Work ; }, abstract = {OBJECTIVES: To estimate the economic burden of lung cancer and mesothelioma due to occupational and para-occupational asbestos exposure in Canada.

METHODS: We estimate the lifetime cost of newly diagnosed lung cancer and mesothelioma cases associated with occupational and para-occupational asbestos exposure for calendar year 2011 based on the societal perspective. The key cost components considered are healthcare costs, productivity and output costs, and quality of life costs.

RESULTS: There were 427 cases of newly diagnosed mesothelioma cases and 1904 lung cancer cases attributable to asbestos exposure in 2011 for a total of 2331 cases. Our estimate of the economic burden is $C831 million in direct and indirect costs for newly identified cases of mesothelioma and lung cancer and $C1.5 billion in quality of life costs based on a value of $C100 000 per quality-adjusted life year. This amounts to $C356 429 and $C652 369 per case, respectively.

CONCLUSIONS: The economic burden of lung cancer and mesothelioma associated with occupational and para-occupational asbestos exposure is substantial. The estimate identified is for 2331 newly diagnosed, occupational and para-occupational exposure cases in 2011, so it is only a portion of the burden of existing cases in that year. Our findings provide important information for policy decision makers for priority setting, in particular the merits of banning the mining of asbestos and use of products containing asbestos in countries where they are still allowed and also the merits of asbestos removal in older buildings with asbestos insulation.}, } @article {pmid28756413, year = {2018}, author = {Reid, A and Merler, E and Peters, S and Jayasinghe, N and Bressan, V and Franklin, P and Brims, F and de Klerk, NH and Musk, AW}, title = {Migration and work in postwar Australia: mortality profile comparisons between Australian and Italian workers exposed to blue asbestos at Wittenoom.}, journal = {Occupational and environmental medicine}, volume = {75}, number = {1}, pages = {29-36}, doi = {10.1136/oemed-2017-104322}, pmid = {28756413}, issn = {1470-7926}, mesh = {Adult ; Asbestos/*adverse effects ; Asbestos, Crocidolite/*adverse effects ; Asbestosis/etiology/*mortality ; Cohort Studies ; *Emigrants and Immigrants ; Employment ; *Ethnicity ; Female ; Humans ; Italy ; Lung Neoplasms/etiology/*mortality ; Male ; Manufacturing Industry ; Mesothelioma/etiology/*mortality ; Mesothelioma, Malignant ; Mining ; Occupational Exposure/*adverse effects/analysis ; Proportional Hazards Models ; Transients and Migrants ; Western Australia ; Young Adult ; }, abstract = {OBJECTIVES: Three hundred and thirty thousand Italians arrived in Australia between 1945 and 1966, many on assisted passage schemes where the worker agreed to a 2-year unskilled employment contract. Italians were the largest of 52 migrant groups employed at the Wittenoom blue asbestos mining and milling operation. We compare mortality from asbestos-related diseases among Italian and Australian workers employed at Wittenoom.

METHODS: A cohort of 6500 male workers was established from employment records and followed up at state and national mortality and cancer registries. SMRs were calculated to compare mortality with the Western Australian male population. Time-varying Cox proportional hazards models compared the risk of mesothelioma between Australian and Italian workers.

RESULTS: 1031 Italians and 3465 Australians worked at Wittenoom between 1943 and 1966. Duration of employment was longer for the Italian workers, although the concentration of exposure was similar. The mesothelioma mortality rate per 100 000 was higher in Italians (184, 95% CI 148 to 229) than Australians (128, 95% CI 111 to 149). The risk of mesothelioma was greater than twofold (HR 2.27, 95% CI 1.43 to 3.60) in Italians at the lowest asbestos exposure category (<10 fibre years/per mL).

CONCLUSIONS: A hierarchy in migration, isolation and a shortage of workers led to Italians at Wittenoom incurring higher cumulative exposure to blue asbestos and subsequently a greater rate of malignant mesothelioma than Australian workers.

IMPACT: Poor working conditions and disparities between native and foreign-born workers has had a detrimental and differential impact on the long-term health of the workforce.}, } @article {pmid28749105, year = {2017}, author = {Sawanyawisuth, K and Furuya, S and Park, EK and Myong, JP and Ramos-Bonilla, JP and Chimed Ochir, O and Takahashi, K}, title = {Compensation for Asbestos-Related Diseases in Japan: Utilization of Standard Classifications of Industry and Occupations.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {18}, number = {7}, pages = {1779-1782}, pmid = {28749105}, issn = {2476-762X}, abstract = {Background: Asbestos-related diseases (ARD) are occupational hazards with high mortality rates. To identify asbestos exposure by previous occupation is the main issue for ARD compensation for workers. This study aimed to identify risk groups by applying standard classifications of industries and occupations to a national database of compensated ARD victims in Japan. Methods: We identified occupations that carry a risk of asbestos exposure according to the International Standard Industrial Classification of All Economic Activities (ISIC). ARD compensation data from Japan between 2006 and 2013 were retrieved. Each compensated worker was classified by job section and group according to the ISIC code. Risk ratios for compensation were calculated according to the percentage of workers compensated because of ARD in each ISIC category. Results: In total, there were 6,916 workers with ARD who received compensation in Japan between 2008 and 2013. ISIC classification section F (construction) had the highest compensated risk ratio of 6.3. Section C (manufacturing) and section F (construction) had the largest number of compensated workers (2,868 and 3,463, respectively). In the manufacturing section C, 9 out of 13 divisions had a risk ratio of more than 1. For ISIC divisions in the construction section, construction of buildings (division 41) had the highest number of workers registering claims (2,504). Conclusion: ISIC classification of occupations that are at risk of developing ARD can be used to identify the actual risk of workers’ compensation at the national level.}, } @article {pmid28744908, year = {2017}, author = {Kohyama, N and Fujiki, M and Kishimoto, T and Morinaga, K}, title = {Lung cancer in a patient with predominantly short tremolite fibers in his lung.}, journal = {American journal of industrial medicine}, volume = {60}, number = {9}, pages = {831-838}, doi = {10.1002/ajim.22748}, pmid = {28744908}, issn = {1097-0274}, mesh = {Aged, 80 and over ; Asbestos, Amphibole/*isolation & purification/toxicity ; *Extraction and Processing Industry ; Humans ; Lung/pathology ; Lung Neoplasms/*etiology ; Male ; Occupational Diseases/*etiology ; Parenchymal Tissue/pathology ; Particle Size ; }, abstract = {The carcinogenicity of short tremolite fibers in human has not been cleared and has been argued hitherto. A lung cancer patient had worked at a gabbro quarry. Particles isolated from the excised lung parenchyma of the patient were measured for asbestos bodies (ABs) and asbestos fibers (AFs). The concentrations of ABs were 3964 AB/g dry lung, and AFs were 5.60 × 106 fibers/g dry lung (>5 um in length) and 22.5 × 106 fibers/g dry lung (>1 um in length). AFs were mostly tremolite fibers and under 7 um in length (mean length 4.0 um, standard deviation 2.8 um). Almost all fibers were <10 um in length and an aspect ratio (AR) of <20:1 and ≥3:1. The patient had never smoked. His wife, who had worked with him in the quarry, had died of pleural mesothelioma. This study strongly indicates that such short tremolite fibers will induce lung cancer and possibly mesothelioma in human.}, } @article {pmid28740198, year = {2017}, author = {Granieri, A}, title = {The Drive For Self-Assertion And The Reality Principle In A Patient With Malignant Pleural Mesothelioma: The History of Giulia.}, journal = {American journal of psychoanalysis}, volume = {77}, number = {3}, pages = {285-294}, doi = {10.1057/s11231-017-9099-0}, pmid = {28740198}, issn = {1573-6741}, mesh = {Asbestos/*adverse effects ; Family/*psychology ; Humans ; Italy ; Mesothelioma/*psychology ; Pleural Neoplasms/*psychology ; *Social Support ; *Truth Disclosure ; }, abstract = {Life in a contaminated environment is often marked by a cumulative psychological trauma that exhibits a variety of social-environmental aspects. This is why I suggested a psychotherapeutic group intervention for the population of Casale Monferrato, a municipality in Northern Italy that is sadly renowned for asbestos-related events and the high mortality rate of its inhabitants. Groupality appears to show the point of contact between psyche and soma, while also promoting the birth of a more realistic approach to the various levels of suffering and their configuration. The multifamily approach seemed to be the most adequate to elaborate the feelings of rage and fear that are concurrent with the aerial contagion. In the "long wave" of group work we have learned to work with participants as well as with empty chairs, the ghosts of the dead: live traces in the mind. Whereas the mind recovers the possibility of entering into a dialogue with the feelings connected to the trauma, without bypassing them towards actions that are apparently more assertive of one's sense of Ego, the will of conciliation can reactivate a thought that is oriented towards the plane of reality.}, } @article {pmid28724330, year = {2017}, author = {Bakker, E and Guazzelli, A and Ashtiani, F and Demonacos, C and Krstic-Demonacos, M and Mutti, L}, title = {Immunotherapy advances for mesothelioma treatment.}, journal = {Expert review of anticancer therapy}, volume = {17}, number = {9}, pages = {799-814}, doi = {10.1080/14737140.2017.1358091}, pmid = {28724330}, issn = {1744-8328}, mesh = {Adaptive Immunity/immunology ; Animals ; Biomarkers/metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; Immunity, Innate/immunology ; Immunotherapy/*methods ; Mesothelioma/immunology/pathology/*therapy ; Prognosis ; Survival Rate ; Tumor Microenvironment ; }, abstract = {Mesothelioma is a rare type of cancer that is strongly tied to asbestos exposure. Despite application of different modalities such as chemotherapy, radiotherapy and surgery, patient prognosis remains very poor and therapies are ineffective. Much research currently focuses on the application of novel approaches such as immunotherapy towards this disease. Areas covered: The types, stages and aetiology of mesothelioma are detailed, followed by a discussion of the current treatment options such as radiotherapy, surgery, and chemotherapy. A description of innate and adaptive immunity and the principles and justification of immunotherapy is also included. Clinical trials for different immunotherapeutic modalities are described, and lastly the article closes with an expert commentary and five-year view, the former of which is summarised below. Expert commentary: Current efforts for novel mesothelioma therapies have been limited by attempting to apply treatments from other cancers, an approach which is not based on a solid understanding of mesothelioma biology. In our view, the influence of the hostile, hypoxic microenvironment and the gene expression and metabolic changes that resultantly occur should be characterised to improve therapies. Lastly, clinical trials should focus on overall survival rather than surrogate endpoints to avoid bias and inaccurate reflections of treatment effects.}, } @article {pmid28713671, year = {2017}, author = {Chen, Z and Gaudino, G and Pass, HI and Carbone, M and Yang, H}, title = {Diagnostic and prognostic biomarkers for malignant mesothelioma: an update.}, journal = {Translational lung cancer research}, volume = {6}, number = {3}, pages = {259-269}, pmid = {28713671}, issn = {2218-6751}, support = {R01 CA160715/CA/NCI NIH HHS/United States ; R01 CA198138/CA/NCI NIH HHS/United States ; }, abstract = {Malignant mesothelioma (MM) is an aggressive and lethal cancer, mostly related to inhalation of asbestos and erionite fibers. MM is associated with poor prognosis, because of its resistance to current therapies, even if higher survival occurs in patients diagnosed and treated when at stage I of the disease. However, these do not exceed 5% of the total number of cases, due to the inadequacy of the existing biomarkers for early and accurate diagnosis. Therefore, new effective biomarkers are needed for MM detection at earlier stages and to develop tailored therapies. Here we review the most promising biomarkers in MM to date: mesothelin, soluble mesothelin-related peptides (SMRPs), megakaryocyte potentiating factor (MPF), Osteopontin (OPN), Fibulin-3, high mobility group B1 (HMGB1), microRNAs (miRNAs), multiplex protein signatures. The validation of these biomarkers will allow their use, alone or in combination, for monitoring individuals from cohorts at risk of MM and attaining early detection of MM that is instrumental in improving patient survival.}, } @article {pmid28713670, year = {2017}, author = {Singh, A and Pruett, N and Hoang, CD}, title = {In vitro experimental models of mesothelioma revisited.}, journal = {Translational lung cancer research}, volume = {6}, number = {3}, pages = {248-258}, pmid = {28713670}, issn = {2218-6751}, abstract = {Malignant pleural mesothelioma (MPM) is a biologically unusual, highly aggressive cancer that defies current multimodality treatments. Epidemiologic data suggest that this malignancy has not abated despite increasingly strict environmental regulations on asbestos, the putative causative agent for sporadic cases. An incomplete understanding of all the factors mechanistically driving mesothelioma is largely responsible for the current lack of curative treatments. Many approaches have been employed to ascertain the step-by-step molecular events involved in mesothelioma oncogenesis including in vitro, small animal in vivo, and human experimental models; though clearly defined, druggable mechanisms still are elusive. Importantly, the foundation of the latest accepted model of tumor initiation is derived from in vitro systems. A thorough review of in vitro mesothelioma oncogenesis models may suggest further opportunities for discovery.}, } @article {pmid28706912, year = {2017}, author = {Sun, HH and Vaynblat, A and Pass, HI}, title = {Diagnosis and prognosis-review of biomarkers for mesothelioma.}, journal = {Annals of translational medicine}, volume = {5}, number = {11}, pages = {244}, pmid = {28706912}, issn = {2305-5839}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive disease arising in pleural cell lining and is associated with asbestos exposure. Today, there is a rising incidence of MPM reaching 3,000 annual cases nationally, primarily from the large population occupationally exposed to asbestos between 1940 and 1980. With a prolonged latency period, presenting clinically 10 to 40 years after exposure, MPM is often diagnosed in late stages and presents median survival time of less than 12 months. There is a serious need for improvement in prognostic and diagnostic tools for MPM. Recent investigation and discovery of various biomarkers has shown promise, including Osteopontin, Fibulin-3, Soluble Mesothelin-Related Proteins (SMRP), High Mobility Group Box 1 (HMGB1), micro-RNA's, peripheral blood-based markers, and Slow Off-rate Modified Aptamer (SOMAmer) proteomic assays. In this review, we explore these current major biomarkers and their prognostic and diagnostic potential, highlighting the most recent large studies and developments for each. While progress has been made in mesothelioma research, many questions remain unanswered. Increased international cooperation is necessary for improving validity of results for current biomarkers through repeated investigation and increasing cohort sizes, as well as for the continued search for new and better markers.}, } @article {pmid28706907, year = {2017}, author = {Emri, SA}, title = {The Cappadocia mesothelioma epidemic: its influence in Turkey and abroad.}, journal = {Annals of translational medicine}, volume = {5}, number = {11}, pages = {239}, pmid = {28706907}, issn = {2305-5839}, abstract = {The epidemic of mesothelioma in Cappadocia, Turkey, is unprecedented in medical history. In three Cappadocian villages, Karain, Tuzkoy and "old" Sarihidir, about 50% of all deaths (including neonatal deaths and traffic fatalities) have been caused by mesothelioma. No other epidemic in medical history has caused such a high incidence of death. This is even more unusual when considering that (I) epidemics are caused by infectious agents, not cancer, and (II) mesothelioma is a rare cancer. World-wide mesothelioma incidence varies between 1/10[6] in areas with no asbestos industry to about 10-30/10[6] in areas with asbestos industry. This article reviews how the mesothelioma epidemic was discovered in Cappadocia by Dr. Baris (my mentor), how we initially linked the epidemic to erionite exposure, and later (with Dr. Carbone) to the interaction between genetic predisposition and environmental exposure. Our team's work had an important positive impact on the lives of those living in Cappadocia and also in many genetically predisposed families living around the world. I will discuss how the work that started in three remote Cappadocian villages led to the award of a NCI P01 grant to support our studies. Our studies proved that genetics modulates mineral fiber carcinogenesis and led to the discovery that carriers of germline BAP1 mutations have a very high risk of developing mesothelioma and other malignancies. A new, very active field of research developed following our discoveries to elucidate the mechanism by which BAP1 modulates mineral fiber carcinogenesis as well as to identify additional genes that when mutated increase the risk of mesothelioma and other environmentally related cancers. I am the only surviving member of this research team who saw all the phases of this research and I believe it is important to provide an accurate report, which hopefully will inspire others.}, } @article {pmid28706906, year = {2017}, author = {Carbone, M and Yang, H}, title = {Mesothelioma: recent highlights.}, journal = {Annals of translational medicine}, volume = {5}, number = {11}, pages = {238}, pmid = {28706906}, issn = {2305-5839}, support = {R01 CA160715/CA/NCI NIH HHS/United States ; R01 CA198138/CA/NCI NIH HHS/United States ; }, abstract = {Recent discoveries have elucidated some of the mechanisms responsible for the development of mesothelioma. These discoveries are: (I) the critical role of chronic inflammation in promoting mesothelioma growth, driven by the release of high mobility group box protein-1 (HMGB1) following asbestos deposition in tissues and its potential role as a biomarker to identify asbestos exposed individuals and mesothelioma patients; (II) the discovery that inherited heterozygous germline mutations of the deubiquitylase BRCA-associated protein 1 (BAP1) cause a high incidence of mesothelioma in some families; and that (III) germline BAP1 mutations lower the threshold of asbestos required to cause mesothelioma in mice, evidence of gene X environment interaction. These findings together with the identification of novel serum biomarkers, including HMGB1, Fibulin-3, etc., promise to revolutionize screening and treatment of this malignancy in the coming years.}, } @article {pmid28706904, year = {2017}, author = {Kim, J and Bhagwandin, S and Labow, DM}, title = {Malignant peritoneal mesothelioma: a review.}, journal = {Annals of translational medicine}, volume = {5}, number = {11}, pages = {236}, pmid = {28706904}, issn = {2305-5839}, abstract = {Mesothelioma is a malignancy of serosal membranes. It is most commonly encountered in the visceral pleura with the second most common location in the peritoneum. The diagnosis is very rare and has been linked to toxic exposure to industrial pollutants, especially asbestos. Malignant peritoneal mesothelioma (MPM) commonly presents with diffuse, extensive spread throughout the abdomen with rare metastatic spread beyond the abdominal cavity. Due to its rarity and nonspecific symptoms, it is usually diagnosed late when the disease burden is extensive. Because pleural mesothelioma is more common than MPM, most research has been on the pleural variant and extrapolated for MPM. While treatment advances have been made for MPM, the disease is universally fatal from either abdominal complications secondary to the spread of disease or starvation. Untreated, the life expectancy is less than a year. Cytoreductive surgery (CRS) with heated intraperitoneal chemotherapy (HIPEC) has become the mainstay of therapy with systemic therapies still being developed. We will review the epidemiology of MPM and discuss diagnostic and treatment strategies.}, } @article {pmid28706903, year = {2017}, author = {Murphy, DJ and Gill, RR}, title = {Overview of treatment related complications in malignant pleural mesothelioma.}, journal = {Annals of translational medicine}, volume = {5}, number = {11}, pages = {235}, pmid = {28706903}, issn = {2305-5839}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive malignant neoplasm of the pleura related to asbestos exposure. Despite recent advances in therapy for MPM, the prognosis remains poor, with considerable treatment associated morbidity. Radiological assessment plays a central role in the timely identification and subsequent management of treatment related complications in MPM. This review highlights common and uncommon complications associated with and encountered in the post treatment phase.}, } @article {pmid28706902, year = {2017}, author = {Noonan, CW}, title = {Environmental asbestos exposure and risk of mesothelioma.}, journal = {Annals of translational medicine}, volume = {5}, number = {11}, pages = {234}, pmid = {28706902}, issn = {2305-5839}, support = {P30 GM103338/GM/NIGMS NIH HHS/United States ; }, abstract = {Mesothelioma is commonly considered an occupational disease occurring as a result of asbestos exposure in the workplace. Several avenues for environmental asbestos exposures have been described and may be associated with asbestos related disease, including mesothelioma. Worker take-home asbestos, or para-occupational exposure, has been well documented and is the most commonly reported pathway for asbestos exposure among mesothelioma cases that do not have history of occupational asbestos exposure. Observational studies have evaluated several communities with elevated mesothelioma incidence and environmental exposures attributed to local asbestos-related industries. Potential, but uncertain, mesothelioma risk also may be associated with general population asbestos exposure through contact with asbestos-containing commercial products, particularly housing materials that can be easily disturbed through normal activity. Finally, studies have described elevated mesothelioma incidence in several areas where populations are exposed to naturally occurring asbestos materials. These various environmental asbestos exposure pathways are poorly understood, and further studies should be pursued to evaluate their respective importance for population mesothelioma risk.}, } @article {pmid28704762, year = {2017}, author = {Bonelli, MA and Digiacomo, G and Fumarola, C and Alfieri, R and Quaini, F and Falco, A and Madeddu, D and La Monica, S and Cretella, D and Ravelli, A and Ulivi, P and Tebaldi, M and Calistri, D and Delmonte, A and Ampollini, L and Carbognani, P and Tiseo, M and Cavazzoni, A and Petronini, PG}, title = {Combined Inhibition of CDK4/6 and PI3K/AKT/mTOR Pathways Induces a Synergistic Anti-Tumor Effect in Malignant Pleural Mesothelioma Cells.}, journal = {Neoplasia (New York, N.Y.)}, volume = {19}, number = {8}, pages = {637-648}, pmid = {28704762}, issn = {1476-5586}, mesh = {Antineoplastic Agents/pharmacology ; Cell Cycle/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Cellular Senescence/drug effects ; Cyclin-Dependent Kinase 4/*antagonists & inhibitors ; Cyclin-Dependent Kinase 6/*antagonists & inhibitors ; Drug Synergism ; Humans ; Lung Neoplasms/metabolism ; Mesothelioma/metabolism ; Mesothelioma, Malignant ; Phosphatidylinositol 3-Kinases/*metabolism ; Piperazines/pharmacology ; Protein Kinase Inhibitors/*pharmacology ; Proto-Oncogene Proteins c-akt/*metabolism ; Pyridines/pharmacology ; Signal Transduction/*drug effects ; TOR Serine-Threonine Kinases/*metabolism ; }, abstract = {Malignant pleural mesothelioma (MPM) is a progressive malignancy associated to the exposure of asbestos fibers. The most frequently inactivated tumor suppressor gene in MPM is CDKN2A/ARF, encoding for the cell cycle inhibitors p16[INK4a] and p14[ARF], deleted in about 70% of MPM cases. Considering the high frequency of alterations of this gene, we tested in MPM cells the efficacy of palbociclib (PD-0332991), a highly selective inhibitor of cyclin-dependent kinase (CDK) 4/6. The analyses were performed on a panel of MPM cell lines and on two primary culture cells from pleural effusion of patients with MPM. All the MPM cell lines, as well as the primary cultures, were sensitive to palbociclib with a significant blockade in G0/G1 phase of the cell cycle and with the acquisition of a senescent phenotype. Palbociclib reduced the phosphorylation levels of CDK6 and Rb, the expression of myc with a concomitant increased phosphorylation of AKT. Based on these results, we tested the efficacy of the combination of palbociclib with the PI3K inhibitors NVP-BEZ235 or NVP-BYL719. After palbociclib treatment, the sequential association with PI3K inhibitors synergistically hampered cell proliferation and strongly increased the percentage of senescent cells. In addition, AKT activation was repressed while p53 and p21 were up-regulated. Interestingly, two cycles of sequential drug administration produced irreversible growth arrest and senescent phenotype that were maintained even after drug withdrawal. These findings suggest that the sequential association of palbociclib with PI3K inhibitors may represent a valuable therapeutic option for the treatment of MPM.}, } @article {pmid28691999, year = {2017}, author = {Pira, E and Coggiola, M and Ciocan, C and Romano, C and La Vecchia, C and Pelucchi, C and Boffetta, P}, title = {Mortality of Talc Miners and Millers From Val Chisone, Northern Italy: An Updated Cohort Study.}, journal = {Journal of occupational and environmental medicine}, volume = {59}, number = {7}, pages = {659-664}, doi = {10.1097/JOM.0000000000000992}, pmid = {28691999}, issn = {1536-5948}, mesh = {Cause of Death ; Cohort Studies ; Gastrointestinal Neoplasms/mortality ; Humans ; Italy/epidemiology ; Lung Neoplasms/mortality ; Male ; Mesothelioma/mortality ; *Mining ; Mouth Neoplasms/mortality ; Neoplasms/*mortality ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/mortality ; Silicosis/*mortality ; Talc/*adverse effects ; Urinary Bladder Neoplasms/mortality ; }, abstract = {OBJECTIVE: The aim of this study was to update the analysis of mortality of a cohort of talc miners and millers in Northern Italy.

METHODS: We analyzed the mortality during 1946 to 2013 of 1722 male workers in an asbestos-free talc mine (1166 miners and 556 millers) employed during 1946 to 1995.

RESULTS: The overall standardized mortality ratio (SMR) was 1.24 [95% confidence interval (95% CI) 1.17 to 1.32]; no deaths were observed from pleural cancer; mortality from lung cancer was not increased. Mortality from pneumoconiosis was increased (SMR 26.62; 95% CI 20.71 to 33.69), in particular among miners, and was associated with duration of employment and time since first employment.

CONCLUSIONS: We confirmed the lack of association between exposure to asbestos-free talc, lung cancer, and mesothelioma. Increased mortality from pneumoconiosis among miners is attributable to past exposure to silica.}, } @article {pmid28687356, year = {2017}, author = {Betti, M and Casalone, E and Ferrante, D and Aspesi, A and Morleo, G and Biasi, A and Sculco, M and Mancuso, G and Guarrera, S and Righi, L and Grosso, F and Libener, R and Pavesi, M and Mariani, N and Casadio, C and Boldorini, R and Mirabelli, D and Pasini, B and Magnani, C and Matullo, G and Dianzani, I}, title = {Germline mutations in DNA repair genes predispose asbestos-exposed patients to malignant pleural mesothelioma.}, journal = {Cancer letters}, volume = {405}, number = {}, pages = {38-45}, doi = {10.1016/j.canlet.2017.06.028}, pmid = {28687356}, issn = {1872-7980}, mesh = {Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Carcinogens/*toxicity ; DNA Repair/*genetics ; Environmental Exposure/*adverse effects ; Environmental Pollutants/*toxicity ; Female ; *Genetic Predisposition to Disease ; *Germ-Line Mutation ; Humans ; Lung Neoplasms/etiology/*genetics ; Male ; Mesothelioma/etiology/*genetics ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/etiology/*genetics ; Risk Factors ; Tumor Suppressor Proteins/genetics ; Ubiquitin Thiolesterase/genetics ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer caused by asbestos exposure. An inherited predisposition has been suggested to explain multiple cases in the same family and the observation that not all individuals highly exposed to asbestos develop the tumor. Germline mutations in BAP1 are responsible for a rare cancer predisposition syndrome that includes predisposition to mesothelioma. We hypothesized that other genes involved in hereditary cancer syndromes could be responsible for the inherited mesothelioma predisposition. We investigated the prevalence of germline variants in 94 cancer-predisposing genes in 93 MPM patients with a quantified asbestos exposure. Ten pathogenic truncating variants (PTVs) were identified in PALB2, BRCA1, FANCI, ATM, SLX4, BRCA2, FANCC, FANCF, PMS1 and XPC. All these genes are involved in DNA repair pathways, mostly in homologous recombination repair. Patients carrying PTVs represented 9.7% of the panel and showed lower asbestos exposure than did all the other patients (p = 0.0015). This suggests that they did not efficiently repair the DNA damage induced by asbestos and leading to carcinogenesis. This study shows that germline variants in several genes may increase MPM susceptibility in the presence of asbestos exposure and may be important for specific treatment.}, } @article {pmid28685333, year = {2018}, author = {Cui, Y and Ma, J and Ye, W and Han, Z and Dong, F and Deng, J and Zhang, Q}, title = {Chrysotile and rock wool fibers induce chromosome aberrations and DNA damage in V79 lung fibroblast cells.}, journal = {Environmental science and pollution research international}, volume = {25}, number = {23}, pages = {22328-22333}, pmid = {28685333}, issn = {1614-7499}, support = {41130746//Key Program of National Nature Science Project of China/ ; 41472046//National Natural Fund Project of China/ ; 14JC0126//Department of Sichuan Province Natural Science Foundation of China/ ; }, mesh = {Animals ; Asbestos, Serpentine/administration & dosage/*toxicity ; Cell Line ; China ; Chromosome Aberrations/*drug effects ; Cricetulus ; DNA Damage/*drug effects ; Dose-Response Relationship, Drug ; Fibroblasts/drug effects/physiology ; Lung/*cytology/drug effects ; Micronucleus Tests ; Mineral Fibers/*toxicity ; Mutagens/toxicity ; Single-Cell Analysis/methods ; }, abstract = {According to global estimates, at least 107,000 people die each year from asbestos-related lung cancer, mesothelioma, and asbestosis resulting from occupational exposure. Chrysotile accounts for approximately 90% of asbestos used worldwide. Artificial substitutes can also be cytotoxic to the same degree as chrysotile. But only a few researchers focused on their genetic effects and mutagenicity information which is useful in evaluating the carcinogenicity of chemicals. In this study, chrysotile from Mangnai, Qinghai, China, and an artificial substitute, rock wool fiber were prepared as suspensions and were tested at concentrations of 50, 100, and 200 μg/ml in V79 lung fibroblasts. Chromosome aberrations were detected by micronucleus assay after exposure for 24 h, and DNA damage were estimated by single cell gel electrophoresis after exposure for 12, 24, or 48 h. According to the results, chrysotile and rock wool fibers caused micronuclei to form in a dose-dependent manner in V79 cells; olive tail moment values increased in a dose- and time-dependent manner. When V79 cells were exposed to a concentration of 200 μg/ml, the degree of DNA damage induced by chrysotile fibers was greater than rock wool fibers. Our study suggests that both chrysotile and rock wool fibers could induce chromosome aberrations and DNA damage. These materials are worthy of further study.}, } @article {pmid28685091, year = {2017}, author = {Uguen, M and Dewitte, JD and Marcorelles, P and Loddé, B and Pougnet, R and Saliou, P and De Braekeleer, M and Uguen, A}, title = {Asbestos-related lung cancers: A retrospective clinical and pathological study.}, journal = {Molecular and clinical oncology}, volume = {7}, number = {1}, pages = {135-139}, pmid = {28685091}, issn = {2049-9450}, abstract = {Exposure to asbestos results in serious risks of developing mesothelioma and lung cancer. The link between asbestos exposure and lung carcinoma is well established. Nevertheless, precise histopathological data are poorly considered when investigating the asbestos-cancer link in a compensatory approach. In the present study, we aim to describe the features of individuals with compensated lung cancer who were referred to an occupational disease center, regarding occupational exposure to asbestos, smoking history and pathological data. We led a retrospective study of compensated ARLC cases seen in our occupational disease center between 2003 and 2013. A total of 146 men were included (mean age at diagnosis, 63.2 years) of whom approximately 90% were heavy current or former smokers (mean value, 30.4 packs/year). The major industries associated with the lung cancer cases were shipbuilding (69.9%), and building construction (7.5%) in this harbor region. The results of the present study showed that lung upper lobe was most prevalent (61.6%) and an excess of adenocarcinoma was found (45.9%), followed by squamous cell carcinoma (38.4%) as well as thoracic sarcomas (2.1%). Neoplasm was not histologically proven in 6.8% of the cases. Subsequent pathology examinations also reclassified 2 tumors as metastases from esophageal and laryngeal origins. In conclusion, smoking prevention should be encouraged in asbestos-exposed workers as reflected by the number of smokers with asbestos-related lung cancer. Thus, histological data should be considered further to evaluate the potent relationship between asbestos exposure and lung malignancy, especially in a compensatory approach.}, } @article {pmid28680295, year = {2017}, author = {Abós-Herràndiz, R and Rodriguez-Blanco, T and Garcia-Allas, I and Rosell-Murphy, IM and Albertí-Casas, C and Tarrés, J and Krier-Günther, I and Martinez-Artés, X and Orriols, R and Grimau-Malet, I and Canela-Soler, J}, title = {Risk Factors of Mortality from All Asbestos-Related Diseases: A Competing Risk Analysis.}, journal = {Canadian respiratory journal}, volume = {2017}, number = {}, pages = {9015914}, pmid = {28680295}, issn = {1916-7245}, mesh = {Age Factors ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Asbestosis/*mortality ; Cohort Studies ; Environmental Exposure/statistics & numerical data ; Female ; Humans ; Incidence ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; Middle Aged ; Mortality ; Occupational Diseases/mortality ; Occupational Exposure/*statistics & numerical data ; Peritoneal Neoplasms/*mortality ; Pleural Neoplasms/*mortality ; Proportional Hazards Models ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Sex Factors ; Smoking/epidemiology ; Spain/epidemiology ; }, abstract = {BACKGROUND: The mortality from all malignant and nonmalignant asbestos-related diseases remains unknown. The authors assessed the incidence and risk factors for all asbestos-related deaths.

METHODS: The sample included 544 patients from an asbestos-exposed community in the area of Barcelona (Spain), between Jan 1, 1970, and Dec 31, 2006. Competing risk regression through a subdistribution hazard analysis was used to estimate risk factors for the outcomes.

RESULTS: Asbestos-related deaths were observed in 167 (30.7%) patients and 57.5% of these deaths were caused by some type of mesothelioma. The incidence rate after diagnosis was 3,600 per 100,000 person-years. In 7.5% of patients death was non-asbestos-related, while pleural and peritoneal mesothelioma were identified in 87 (16.0%) and 18 (3.3%) patients, respectively.

CONCLUSIONS: Age, sex, household exposure, cumulative nonmalignant asbestos-related disease, and single malignant pathology were identified as risk factors for asbestos-related death. These findings suggest the need to develop a preventive approach to the community and to improve the clinical follow-up process of these patients.}, } @article {pmid28669341, year = {2018}, author = {Zanellato, I and Colangelo, D and Osella, D}, title = {JQ1, a BET Inhibitor, Synergizes with Cisplatin and Induces Apoptosis in Highly Chemoresistant Malignant Pleural Mesothelioma Cells.}, journal = {Current cancer drug targets}, volume = {18}, number = {8}, pages = {816-828}, doi = {10.2174/1568009617666170623101722}, pmid = {28669341}, issn = {1873-5576}, mesh = {A549 Cells ; Antineoplastic Agents/*pharmacology ; Apoptosis/*drug effects ; Azepines/*pharmacology ; Cell Cycle Checkpoints/drug effects ; Cell Cycle Proteins ; Cellular Senescence/drug effects ; Cisplatin/*pharmacology ; DNA Breaks/drug effects ; Drug Resistance, Neoplasm/*drug effects ; Drug Synergism ; Drug Therapy, Combination ; Humans ; Lung Neoplasms/*drug therapy/pathology ; Mesothelioma/*drug therapy/pathology ; Mesothelioma, Malignant ; Nuclear Proteins/*antagonists & inhibitors ; Pleural Neoplasms/*drug therapy/pathology ; Proto-Oncogene Proteins c-fos/antagonists & inhibitors ; Proto-Oncogene Proteins c-myc/antagonists & inhibitors ; Transcription Factors/*antagonists & inhibitors ; Transcription, Genetic/drug effects ; Triazoles/*pharmacology ; beta-Galactosidase/metabolism ; }, abstract = {BACKGROUND: Malignant Pleural Mesothelioma (MPM) is an asbestos-associated tumor with poor prognosis and few therapeutic options. JQ1, a selective antagonist of BRD4, modulates transcription of oncogenes, including MPM chemoresistance-associated c-Myc and Fra-1.

OBJECTIVE: We investigated if JQ1 could enhance the efficacy of cisplatin against MPM.

METHODS: The antiproliferative activity of cisplatin in combination with JQ1 was assessed on MPM cell lines representative of the cellular phenotypes of this tumor (epithelioid, sarcomatoid and biphasic), and on one cisplatin resistant sub-line. The combination schedule was optimized adopting a 3Dspheroid model. Drug combination effects were correlated with cell cycle distribution and senescence- associated β-galactosidase positive cells. The expression of c-Myc and Fra-1 proteins and some apoptosis markers was assessed by immunoblotting and RT-qPCR. DNA damage and repair were evaluated by means of alkaline comet assay.

RESULTS: JQ1 in combination with cisplatin elicited additive or synergistic (superadditive) antiproliferative effects on MPM cells, depending on the cell line. The combination showed tumor regression on the 3D-spheroid model. It induced increased apoptosis, along with decreased c-Myc and, sometimes, Fra-1 expression. JQ1 decreased cisplatin-induced DNA breaks in all MPM cells and increased senescence even in less proficient cells, thus enhancing the DNA Damage Response (DDR).

CONCLUSION: The superadditive effect is due to c-Myc repression. The consequent DDR enhancement triggers to apoptosis induction and/or permanent growth arrest (senescence), depending on the MPM cellular context, leading to tumor regression. Thus, the pharmacological modulation of BET activity could represent a promising tool for future MPM therapy.}, } @article {pmid28663314, year = {2017}, author = {Feder, IS and Tischoff, I and Theile, A and Schmitz, I and Merget, R and Tannapfel, A}, title = {The asbestos fibre burden in human lungs: new insights into the chrysotile debate.}, journal = {The European respiratory journal}, volume = {49}, number = {6}, pages = {}, pmid = {28663314}, issn = {1399-3003}, mesh = {Aged ; Aged, 80 and over ; Asbestos, Serpentine/*adverse effects/*analysis ; Autopsy ; Germany ; Humans ; Longitudinal Studies ; Lung/pathology ; Lung Neoplasms/*etiology/surgery ; Male ; Mesothelioma/*etiology/surgery ; Microscopy, Electron ; Middle Aged ; Occupational Exposure/*adverse effects ; Registries ; }, abstract = {The traceability of asbestos fibres in human lungs is a matter of discussion especially for chrysotile. This issue is of high significance for differential diagnosis, risk assessment and occupational compensation. At present no intra-individual longitudinal information is available. This study addresses the question whether the asbestos fibre burden in human lungs decreases with time after exposure cessation.The database of the German Mesothelioma Register was screened for patients with asbestos body counts of at least 500 fibres per gram of wet lung, which had been analysed twice from different tissue excisions at minimum intervals of 4 years.Twelve datasets with individual longitudinal information were discovered with a median interval of about 8 years (range 4-21 years). Both examinations were performed after exposure cessation (median: surgery, 9.5 years; autopsy, 22 years). Pulmonary asbestos fibre burden was stable between both examinations (median 1623/4269 asbestos bodies per gram wet lung). Electron microscopy demonstrated a preponderance of chrysotile (median 80%).This study is the first to present longitudinal intra-individual data about the asbestos fibre burden in living human lungs. The high biopersistence of amphiboles, but also of chrysotile, offers mechanistic explanations for fibre toxicity, especially the long latency period of asbestos-related diseases.}, } @article {pmid28651470, year = {2017}, author = {Finley, BL and Benson, SM and Marsh, GM}, title = {Cosmetic talc as a risk factor for pleural mesothelioma: a weight of evidence evaluation of the epidemiology.}, journal = {Inhalation toxicology}, volume = {29}, number = {4}, pages = {179-185}, doi = {10.1080/08958378.2017.1336187}, pmid = {28651470}, issn = {1091-7691}, mesh = {*Cosmetics ; Humans ; Mesothelioma/*chemically induced ; *Occupational Exposure ; Pleural Neoplasms/*chemically induced ; Risk Factors ; Talc/chemistry/*toxicity ; }, abstract = {OBJECTIVE: Due to some historical (and inaccurate) reports that asbestos might be present in some cosmetic talc products, questions are occasionally raised regarding the potential pleural mesothelioma risks associated with cosmetic talc products. Our objective was to determine the incidence of pleural mesothelioma of individuals exposed to cosmetic talc.

MATERIALS AND METHODS: We conducted a systematic review of the epidemiological literature for cosmetic talc miners and millers and found three occupational cohort studies that evaluated pleural mesothelioma incidence in workers in Italy, Norway, France, and Austria. We conducted a second literature review to evaluate the incidence and mortality of pleural mesothelioma among patients who received talc pleurodesis treatments before 1965 and found retrospective clinical studies including over 300 patients with follow-up ranging from 14 to 40 years.

RESULTS: There were no mesotheliomas reported in any of the cosmetic talc miner and miller cohorts. A pooled analysis of data from the cohort mortality studies indicated that four mesothelioma deaths would have been expected from the 90,022 person-years of observation, and this was associated with 84% and 67% statistical power to observe a 3-fold or 2.5-fold increase in pleural mesothelioma mortality, respectively. None of the patients who received talc pleurodesis treatments developed mesothelioma.

CONCLUSION: We conclude that there is no epidemiological evidence to support the hypothesis that exposure to cosmetic talc is associated with the development of pleural mesothelioma.}, } @article {pmid28634559, year = {2017}, author = {Ideguchi, R and Ashizawa, K and Akashi, S and Shindo, M and Minami, K and Fukuda, T and Irie, J and Fukuda, M and Uetani, M}, title = {Malignant Pleural Mesothelioma with Marked Lymphatic Involvement: A Report of Two Autopsy Cases.}, journal = {Case reports in oncological medicine}, volume = {2017}, number = {}, pages = {6195898}, pmid = {28634559}, issn = {2090-6706}, abstract = {We herein report two cases of malignant pleural mesothelioma with marked lymphangiosis. The patients included a 68-year-old man and a 67-year-old man who both had a history of exposure to asbestos. Computed tomography (CT) on admission showed pleural effusion with pleural thickening. In both cases, a histopathological examination of the pleura confirmed the diagnosis of epithelioid malignant mesothelioma. They received chemotherapy, but the treatment was only palliative. The chest CT assessments during admission revealed marked pleural effusion and mediastinal lymphadenopathy. CT also showed a consolidative mass with bronchovascular bundle and septal thickening in the lungs suggesting pulmonary parenchymal involvement and the lymphangitic spread of the tumor. These CT findings mimicked lung cancer with pleuritis and lymphangitic carcinomatosis. Autopsy was performed in both cases. Macroscopically, the tumor cells infiltrated the lung with the marked lymphatic spread of the tumor. Microscopy also revealed that the tumor had invaded the pulmonary parenchyma with the marked lymphatic spread of the tumor. Although this growth pattern is unusual, malignant pleural mesothelioma should be considered as the differential diagnosis, especially in patients with pleural lesions.}, } @article {pmid28629895, year = {2017}, author = {Kao, SC and Cheng, YY and Williams, M and Kirschner, MB and Madore, J and Lum, T and Sarun, KH and Linton, A and McCaughan, B and Klebe, S and van Zandwijk, N and Scolyer, RA and Boyer, MJ and Cooper, WA and Reid, G}, title = {Tumor Suppressor microRNAs Contribute to the Regulation of PD-L1 Expression in Malignant Pleural Mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {12}, number = {9}, pages = {1421-1433}, doi = {10.1016/j.jtho.2017.05.024}, pmid = {28629895}, issn = {1556-1380}, mesh = {Aged ; B7-H1 Antigen/*biosynthesis/metabolism ; Female ; Humans ; Lung Neoplasms/*genetics/*metabolism/pathology ; Male ; Mesothelioma/*genetics/*metabolism/pathology ; Mesothelioma, Malignant ; MicroRNAs/*genetics ; Pleural Neoplasms/*genetics/*metabolism/pathology ; Prognosis ; Up-Regulation ; }, abstract = {INTRODUCTION: The upregulation of programmed death ligand 1 (PD-L1) is found in many cancers and contributes to evasion of the host's immune defense. In malignant pleural mesothelioma (MPM), PD-L1 expression is associated with the nonepithelioid histological subtype and poor prognosis, but the pathways involved in control of PD-L1 expression in MPM are poorly understood. To address one possible means of PD-L1 regulation we investigated the relationship between dysregulated microRNA levels and PD-L1 expression.

METHODS: PD-L1 expression was analyzed by immunohistochemistry in tissue microarrays prepared from samples from patients undergoing an operation (pleurectomy with or without decortication). MicroRNA expression was analyzed by reverse-transcriptase quantitative polymerase chain reaction. Regulation of PD-L1 expression in cell lines was assessed after transfection with microRNA mimics and small interfering RNAs. Interaction between microRNAs and PD-L1 was analyzed by using argonaute-2 immunoprecipitation and a luciferase reporter assay.

RESULTS: In a series of 72 patients with MPM, 18 (25%) had positive PD-L1 staining, and this was more common in patients with the nonepithelioid subtype (p = 0.01). PD-L1 expression was associated with poor survival (median overall survival 4.0 versus 9.2 months with positive versus negative PD-L1 expression [p < 0.001]), and in multivariate analyses, PD-L1 expression remained a significant adverse prognostic indicator (hazard ratio = 2.2, 95% confidence interval: 1.2-4.1, p < 0.01). In the same patient series, PD-L1 expression was also associated with downregulation of microRNAs previously shown to have tumor suppressor activity in MPM. The median microRNA expression levels of miR-15b, miR-16, miR-193a-3p, miR-195, and miR-200c were significantly lower in the PD-L1-positive samples. Transfecting MPM cell lines with mimics corresponding to miR-15a and miR-16, both of which are predicted to target PD-L1, led to downregulation of PD-L1 mRNA and protein. In addition, miR-193a-3p, with an alternative G-U-containing target site, also caused PD-L1 downregulation.

CONCLUSIONS: Together, these data suggest that tumor suppressor microRNAs contribute to the regulation of PD-L1 expression in MPM.}, } @article {pmid28625623, year = {2017}, author = {Świątkowska, B and Szeszenia-Dąbrowska, N}, title = {Mesothelioma continues to increase even 40 years after exposure - Evidence from long-term epidemiological observation.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {108}, number = {}, pages = {121-125}, doi = {10.1016/j.lungcan.2017.03.012}, pmid = {28625623}, issn = {1872-8332}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Case-Control Studies ; Female ; Follow-Up Studies ; Humans ; Male ; Mesothelioma/*epidemiology/*etiology ; Middle Aged ; Occupational Diseases/epidemiology/etiology ; *Occupational Exposure ; Odds Ratio ; Pleural Neoplasms/epidemiology/etiology ; Poland/epidemiology ; Risk ; Time Factors ; }, abstract = {BACKGROUND: Because asbestos dust is considered one of the most dangerous types of dust for people's health, issues related to the effects of asbestos exposure still remain questions about the role of cessation of exposure.

OBJECTIVES: The aim of the present study was to determine the importance of temporal patterns, especially the time since the end of exposure in the risk of pleural mesothelioma.

METHODS: A total of 131 patients with pleural mesothelioma and 655 frequency matched by gender and year of birth controls enrolled in the health surveillance programme for asbestos-related diseases over the years 2000-2014, were included in the analysis. Conditional logistic regression models were applied to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs).

RESULTS: The results show that the risk of pleural mesothelioma continued to increase even after 40 years since the last exposure. The estimated odds ratio for the subjects who had their last exposure 40 years ago, compared with the odds ratio of those who had their last exposure 5 years ago, was 2.68 (95%CI: 1.16-.621). We also observed that crocidolite exposure was associated with a very high significant mesothelioma risk, 5-fold higher for those working with mixed exposure compared to the subjects who worked only with chrysotile.

CONCLUSIONS: Dose-response relationships in populations occupationally exposed are critical to the study related to environment asbestos contamination. Our findings confirm the strong evidence that mesothelioma risk increases along with the increasing time since exposure termination.}, } @article {pmid28619093, year = {2017}, author = {McDonnell, AM and Cook, A and Robinson, BWS and Lake, RA and Nowak, AK}, title = {Serial immunomonitoring of cancer patients receiving combined antagonistic anti-CD40 and chemotherapy reveals consistent and cyclical modulation of T cell and dendritic cell parameters.}, journal = {BMC cancer}, volume = {17}, number = {1}, pages = {417}, pmid = {28619093}, issn = {1471-2407}, mesh = {Antibodies, Monoclonal/administration & dosage ; Antibodies, Monoclonal, Humanized ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use ; Biomarkers ; CD40 Antigens/antagonists & inhibitors ; Cisplatin/administration & dosage ; Clinical Trials, Phase I as Topic ; Dendritic Cells/*immunology/metabolism ; Female ; Humans ; Immunomodulation/*drug effects ; Immunophenotyping ; Lymphocyte Activation ; Lymphocyte Count ; Male ; Neoplasms/diagnosis/drug therapy/*immunology/metabolism ; Prognosis ; Proportional Hazards Models ; T-Lymphocyte Subsets/*immunology/metabolism ; }, abstract = {BACKGROUND: CD40 signalling can synergise with chemotherapy in preclinical cancer models, and early clinical studies are promising. We set out to define the immunological changes associated with this therapeutic combination to identify biomarkers for a response to the therapy. Here, we present serial immunomonitoring examining dendritic cell and T cell subpopulations over sequential courses of chemoimmunotherapy.

METHODS: Fifteen patients with mesothelioma received up to six 21-day cycles of pemetrexed plus cisplatin chemotherapy and anti-CD40 (CP-870,893). Peripheral blood was collected weekly, and analysed by flow cytometry. Longitudinal immunophenotyping data was analysed by linear mixed modelling, allowing for variation between patients. Exploratory analyses testing for any correlation between overall survival and immunophenotyping data were undertaken up to the third cycle of treatment.

RESULTS: Large statistically significant cyclical variations in the proportions of BDCA-1+, BDCA-2+ and BDCA-3+ dendritic cells were observed, although all subsets returned to baseline levels after each cycle and no significant changes were observed between start and end of treatment. Expression levels of CD40 and HLA-DR on dendritic cells were also cyclically modulated, again without significant change between start and end of treatment. CD8 and CD4 T cell populations, along with regulatory T cells, effector T cells, and markers of proliferation and activation, showed similar patterns of statistically significant cyclical modulation in response to therapy without changes between start and end of treatment. Exploratory analysis of endpoints revealed that patients with a higher than average proportion of BDCA-2+ dendritic cells (p = 0.010) or a higher than average proportion of activated (ICOS+) CD8 T cells (0.022) in pretreatment blood samples had better overall survival. A higher than average proportion of BDCA-3+ dendritic cells was associated with poorer overall survival at both the second (p = 0.008) and third (p = 0.014) dose of anti-CD40.

CONCLUSIONS: Substantial cyclical variations in DC and T cell populations during sequential cycles of chemoimmunotherapy highlight the critical importance of timing of immunological biomarker assessments in interpretation of results and the value of linear mixed modelling in interpretation of longitudinal change over a full treatment course.

TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry number ACTRN12609000294257 (18th May 2009).}, } @article {pmid28614305, year = {2017}, author = {Bononi, A and Giorgi, C and Patergnani, S and Larson, D and Verbruggen, K and Tanji, M and Pellegrini, L and Signorato, V and Olivetto, F and Pastorino, S and Nasu, M and Napolitano, A and Gaudino, G and Morris, P and Sakamoto, G and Ferris, LK and Danese, A and Raimondi, A and Tacchetti, C and Kuchay, S and Pass, HI and Affar, EB and Yang, H and Pinton, P and Carbone, M}, title = {BAP1 regulates IP3R3-mediated Ca[2+] flux to mitochondria suppressing cell transformation.}, journal = {Nature}, volume = {546}, number = {7659}, pages = {549-553}, pmid = {28614305}, issn = {1476-4687}, support = {P30 CA071789/CA/NCI NIH HHS/United States ; R01 CA160715/CA/NCI NIH HHS/United States ; R01 CA198138/CA/NCI NIH HHS/United States ; }, mesh = {Apoptosis/genetics ; Asbestos/toxicity ; Calcium/*metabolism ; Calcium Signaling ; Cell Nucleus/metabolism ; Cell Survival ; *Cell Transformation, Neoplastic/drug effects/radiation effects ; Cells, Cultured ; Cytoplasm/*metabolism ; DNA Damage ; Endoplasmic Reticulum/*metabolism ; Epithelium ; Fibroblasts ; Gene-Environment Interaction ; Humans ; Inositol 1,4,5-Trisphosphate Receptors/*metabolism ; Mitochondria/*metabolism ; Protein Binding ; Protein Stability ; Tumor Suppressor Proteins/deficiency/genetics/*metabolism ; Ubiquitin/metabolism ; Ubiquitin Thiolesterase/deficiency/genetics/*metabolism ; }, abstract = {BRCA1-associated protein 1 (BAP1) is a potent tumour suppressor gene that modulates environmental carcinogenesis. All carriers of inherited heterozygous germline BAP1-inactivating mutations (BAP1[+/-]) developed one and often several BAP1[-/-] malignancies in their lifetime, mostly malignant mesothelioma, uveal melanoma, and so on. Moreover, BAP1-acquired biallelic mutations are frequent in human cancers. BAP1 tumour suppressor activity has been attributed to its nuclear localization, where it helps to maintain genome integrity. The possible activity of BAP1 in the cytoplasm is unknown. Cells with reduced levels of BAP1 exhibit chromosomal abnormalities and decreased DNA repair by homologous recombination, indicating that BAP1 dosage is critical. Cells with extensive DNA damage should die and not grow into malignancies. Here we discover that BAP1 localizes at the endoplasmic reticulum. Here, it binds, deubiquitylates, and stabilizes type 3 inositol-1,4,5-trisphosphate receptor (IP3R3), modulating calcium (Ca[2+]) release from the endoplasmic reticulum into the cytosol and mitochondria, promoting apoptosis. Reduced levels of BAP1 in BAP1[+/-] carriers cause reduction both of IP3R3 levels and of Ca[2+] flux, preventing BAP1[+/-] cells that accumulate DNA damage from executing apoptosis. A higher fraction of cells exposed to either ionizing or ultraviolet radiation, or to asbestos, survive genotoxic stress, resulting in a higher rate of cellular transformation. We propose that the high incidence of cancers in BAP1[+/-] carriers results from the combined reduced nuclear and cytoplasmic activities of BAP1. Our data provide a mechanistic rationale for the powerful ability of BAP1 to regulate gene-environment interaction in human carcinogenesis.}, } @article {pmid28611824, year = {2017}, author = {Kresoja-Rakic, J and Sulemani, M and Kirschner, MB and Ronner, M and Reid, G and Kao, S and Schwaller, B and Weder, W and Stahel, RA and Felley-Bosco, E}, title = {Posttranscriptional Regulation Controls Calretinin Expression in Malignant Pleural Mesothelioma.}, journal = {Frontiers in genetics}, volume = {8}, number = {}, pages = {70}, pmid = {28611824}, issn = {1664-8021}, abstract = {Calretinin (CALB2) is a diagnostic and prognostic marker in malignant pleural mesothelioma (MPM). We previously reported that calretinin expression is regulated at the mRNA level. The presence of a medium-sized (573 nucleotide) 3' untranslated region (3'UTR) predicted to contain binding sites for miR-30a/b/c/d/e and miR-9 as well as an adenine/uridine-rich element (ARE) in all three transcripts arising from the CALB2 gene, suggests that calretinin expression is regulated via posttranscriptional mechanisms. Our aim was to investigate the role of the CALB2-3'UTR in the posttranscriptional regulation of calretinin expression in MPM. CALB2-3'UTR was inserted downstream of the luciferase reporter gene using pmiRGLO vector and reporter expression was determined after transfection into MPM cells. Targeted mutagenesis was used to generate variants harboring mutated miR-30 family and ARE binding sites. Electrophoretic mobility shift assay was used to test for the presence of ARE binding proteins. CALB2-3'UTR significantly decreased luciferase activity in MPM cells. Analysis of mutation in the ARE site revealed a further destabilization of the reporter and human antigen R (HuR) binding to the ARE sequence was detected. The mutation of two miR-30 binding sites abolished CALB2-3'UTR destabilization effect; a transient delivery of miR-30e-5p mimics or anti-miR into MPM cells resulted in a significant decrease/increase of the luciferase reporter expression and calretinin protein, respectively. Moreover, overexpression of CALB2-3'UTR quenched the effect of miR-30e-5p mimics on calretinin protein levels, possibly by sequestering the mimics, thereby suggesting a competitive endogenous RNA network. Finally, by data mining we observed that expression of miR-30e-5p was negatively correlated with the calretinin expression in a cohort of MPM patient samples. Our data show the role of (1) adenine-uridine (AU)-binding proteins in calretinin stabilization and (2) miR-30e-5p in the posttranscriptional negative regulation of calretinin expression via interaction with its 3'UTR. Furthermore, our study demonstrates a possible physiological role of calretinin's alternatively spliced transcripts.}, } @article {pmid28606736, year = {2017}, author = {An, JY and Kim, D and Tanakchi, S and Semerjian, AM and Thomas, A and Boyle, SL and Hassan, R and Metwalli, AR}, title = {Clinical Features and Outcomes of Tunica Vaginalis Mesothelioma: A Case Series From the National Institutes of Health.}, journal = {Clinical genitourinary cancer}, volume = {15}, number = {5}, pages = {e871-e875}, pmid = {28606736}, issn = {1938-0682}, support = {Z99 CL999999//Intramural NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Humans ; Lung Neoplasms/diagnosis/*surgery ; Male ; Mesothelioma/diagnosis/*surgery ; Mesothelioma, Malignant ; Middle Aged ; National Institutes of Health (U.S.) ; Orchiectomy ; Survival Analysis ; Testicular Neoplasms/diagnosis/*surgery ; Treatment Outcome ; United States ; }, abstract = {OBJECTIVE: To present our single-institution experience with management of seven patients with mesothelioma of the tunica vaginalis.

MATERIALS AND METHODS: Our institution database was queried from 2003 to 2014. Clinical, surgical and pathological features were retrospectively collected and evaluated.

RESULTS: Seven patients were identified with tunica vaginalis mesothelioma. Average age at the time of diagnosis was 63.6 years. Four patients presented with hydrocele, one with scrotal mass, one with inguinal mass, and one with spermatocele. Two (28.6%) patients reported possible asbestos exposure. Radical orchiectomy was performed in all patients. Two patients received adjuvant radiotherapy, one patient received both chemotherapy and radiation. All patients were followed up postoperatively with serial imaging detect for recurrence. One of 7 patients in our cohort experienced recurrence at 12 months. Our mean follow-up time on these patients is 52.2 months.

CONCLUSION: Previous reported cases have described poor prognosis of tunica vaginalis mesothelioma despite aggressive surgery and systemic therapy. Our single-institution experience suggests relatively good outcomes with surgery and limited adjuvant therapies. Post treatment surveillance is also imperative and should include imaging routinely within the first 2 years. Negative asbestos exposure screening during history should not eliminate clinical suspicion.}, } @article {pmid28603777, year = {2016}, author = {Napolitano, A and Carbone, M}, title = {Malignant Mesothelioma: Time to Translate?.}, journal = {Trends in cancer}, volume = {2}, number = {9}, pages = {467-474}, pmid = {28603777}, issn = {2405-8033}, support = {R01 CA198138/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antineoplastic Agents/therapeutic use ; Humans ; *Lung Neoplasms/drug therapy/genetics/metabolism ; *Mesothelioma/drug therapy/genetics/metabolism ; Mesothelioma, Malignant ; Molecular Targeted Therapy ; Translational Research, Biomedical ; }, abstract = {Malignant mesothelioma is an aggressive cancer largely associated with asbestos exposure. In this review, we will discuss the significant advancements in our understanding of its genetics and molecular biology and their translational relevance. Remarkable findings included the discovery of germline and somatic mutations of BRCA1 associated protein-1 (BAP1) in patients, and the genome-wide characterization of pathways altered in mesothelioma that could be potentially exploited to design novel therapeutic approaches. Nevertheless, the clinical translation of these molecular findings has been slow and insufficient. In order to rapidly move translation from the bench to the bedside, we believe that cooperative research efforts have to be further endorsed and promoted at all levels.}, } @article {pmid28594258, year = {2017}, author = {Fujimoto, E and Kijima, T and Kuribayashi, K and Negi, Y and Kanemura, S and Mikami, K and Doi, H and Kitajima, K and Nakano, T}, title = {First-line chemotherapy with pemetrexed plus cisplatin for malignant peritoneal mesothelioma.}, journal = {Expert review of anticancer therapy}, volume = {17}, number = {9}, pages = {865-872}, doi = {10.1080/14737140.2017.1340157}, pmid = {28594258}, issn = {1744-8328}, mesh = {Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Cisplatin/administration & dosage ; Disease-Free Survival ; Female ; Fluorodeoxyglucose F18 ; Humans ; Lung Neoplasms/*drug therapy/pathology ; Male ; Mesothelioma/*drug therapy/pathology ; Mesothelioma, Malignant ; Middle Aged ; Pemetrexed/administration & dosage ; Pleural Neoplasms/*drug therapy/pathology ; Positron-Emission Tomography ; Retrospective Studies ; Survival Rate ; Tomography, X-Ray Computed ; Treatment Outcome ; }, abstract = {BACKGROUND: Mesothelioma of peritoneal origin has wider variation in treatment outcomes than mesothelioma of pleural origin, likely because peritoneal mesothelioma comprises borderline malignant variants and aggressive malignant peritoneal mesothelioma (MPeM). This study retrospectively evaluates the efficacy of first-line systemic pemetrexed and cisplatin chemotherapy in MPeM.

RESEARCH DESIGN AND METHODS: Twenty-four patients with histologically proven MPeM were treated with pemetrexed plus cisplatin as a first-line systemic chemotherapy. The response was evaluated radiologically according to standard Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Twenty-two patients underwent [18]F-fluorodeoxyglucose positron emission tomography/(FDG-PET)/computed tomography(CT) at baseline, and 13 were eligible for metabolic assessment.

RESULTS: Two complete responses and 9 partial responses were achieved. Overall response rate and disease control rate were 45.8% and 91.7%, respectively. Median progression-free survival and median overall survival were 11.0 months and 15.8 months, respectively. Wet- type MPeM had significantly longer survival (40.9 months median) than other clinical types (15.5 months) (P = 0.045). The baseline maximum standardized uptake value in 22 patients was 8.93 (range, 2.5-16.77).

CONCLUSIONS: Systemic pemetrexed plus cisplatin is active for MPeM. Disparity with the outcome of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) needs to receive more emphasis, since peritoneal mesothelioma has a 5-year survival rate of 50%.}, } @article {pmid28593073, year = {2017}, author = {Nynäs, P and Pukkala, E and Vainio, H and Oksa, P}, title = {Cancer Incidence in Asbestos-Exposed Workers: An Update on Four Finnish Cohorts.}, journal = {Safety and health at work}, volume = {8}, number = {2}, pages = {169-174}, pmid = {28593073}, issn = {2093-7911}, abstract = {BACKGROUND: We assessed the cancer risks of four different Finnish asbestos-exposed cohorts. We also explored if the cohorts with varying profiles of asbestos exposure exhibited varying relative risks of cancer.

METHODS: The incident cancer cases for the asbestos-exposed worker cohorts were updated to the end of 2012 using the files of the Finnish Cancer Registry. The previously formed cohorts consisted of asbestos mine workers, asbestosis patients, asbestos sprayers, and workers who had taken part in a screening study based on asbestos exposure at work.

RESULTS: The standardized incidence ratio (SIR) for mesothelioma varied from about threefold to > 100-fold in the different cohorts. In the screening cohort the SIR for mesothelioma was highest in 2003-2007, In other cohorts it was more constant in 5-year period inspection. The SIR for lung cancer was about twofold to tenfold in all except the screening cohort. Asbestos sprayers were at the highest risk of mesothelioma and lung cancer.

CONCLUSION: The SIR for mesothelioma is high in all of the cohorts that represent different kinds of asbestos exposure. The smaller SIR for mesothelioma in the screening cohort with lowest level of asbestos exposure might suggest dose-responsiveness between asbestos exposure and mesothelioma. It does seem that the highest risk of lung cancer in these cohorts except in the youngest of the cohorts, the screening cohort, is over. The highest SIR for lung cancer of the asbestosis patient and sprayers cohort is explained by their heavy asbestos exposure.}, } @article {pmid28577549, year = {2017}, author = {Sneddon, S and Patch, AM and Dick, IM and Kazakoff, S and Pearson, JV and Waddell, N and Allcock, RJN and Holt, RA and Robinson, BWS and Creaney, J}, title = {Whole exome sequencing of an asbestos-induced wild-type murine model of malignant mesothelioma.}, journal = {BMC cancer}, volume = {17}, number = {1}, pages = {396}, pmid = {28577549}, issn = {1471-2407}, mesh = {Animals ; Asbestos/*toxicity ; DNA Copy Number Variations/genetics ; Disease Models, Animal ; Genetic Predisposition to Disease ; Humans ; Lung Neoplasms/chemically induced/*genetics/pathology ; Mesothelioma/chemically induced/*genetics/pathology ; Mesothelioma, Malignant ; Mice ; Mutation ; Neoplasm Proteins/*genetics ; Proto-Oncogene Mas ; Signal Transduction/drug effects/genetics ; *Exome Sequencing ; }, abstract = {BACKGROUND: Malignant mesothelioma (MM) is an aggressive cancer of the pleural and peritoneal cavities caused by exposure to asbestos. Asbestos-induced mesotheliomas in wild-type mice have been used extensively as a preclinical model because they are phenotypically identical to their human counterpart. However, it is not known if the genetic lesions in these mice tumours are similar to in the human disease, a prerequisite for any new preclinical studies that target genetic abnormalities.

METHODS: We performed whole exome sequencing of fifteen asbestos-induced murine MM tumour cell lines from BALB/c, CBA and C57BL/6 mouse strains and compared the somatic mutations and copy number variations with those recurrently reported in human MM. We then catalogued and characterised the mutational landscape of the wild-type murine MM tumours. Quantitative RT-PCR was used to interrogate the expression of key MM genes of interest in the mRNA.

RESULTS: Consistent with human MM tumours, we identified homozygous loss of the tumour suppressor Cdkn2a in 14/15 tumours. One tumour retained the first exon of both of the p16INK4a and p19ARF isoforms though this tumour also contained genetic amplification of Myc resulting in increased expression of the c-Myc proto-oncogene in the mRNA. There were no chromosomal losses in either the Bap1 or Nf2 regions. One tumour harbored homozygous loss of Trp53 in the DNA. Mutation rates were similar in tumours generated in the CBA and C57BL/6 strains when compared to human MM. Interestingly, all BALB/c tumour lines displayed high mutational loads, consistent with the known mutator phenotype of the host strain. The Wnt, MAPK and Jak-STAT signaling pathways were found to be the most commonly affected biological pathways. Mutations and copy number deletions also occurred in the Hedgehog and Hippo pathways.

CONCLUSIONS: These data suggest that in the wild-type murine model asbestos causes mesotheliomas in a similar way to in human MM. This further supports the notion that the murine model of MM represents a genuine homologue of the human disease, something uncommon in cancer, and is thus a valuable tool to provide insight into MM tumour development and to aide the search for novel therapeutic strategies.}, } @article {pmid28572505, year = {2017}, author = {}, title = {Correction: Germline BAP1 Mutational Landscape of Asbestos-Exposed Malignant Mesothelioma Patients with Family History of Cancer.}, journal = {Cancer research}, volume = {77}, number = {11}, pages = {3124}, doi = {10.1158/0008-5472.CAN-17-0575}, pmid = {28572505}, issn = {1538-7445}, } @article {pmid28562724, year = {2017}, author = {Trotta, A and Santana, VS and Alazraqui, M}, title = {[Mesothelioma mortality in Argentina, 1980-2013].}, journal = {Salud colectiva}, volume = {13}, number = {1}, pages = {35-44}, doi = {10.18294/sc.2017.1027}, pmid = {28562724}, issn = {1851-8265}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Argentina/epidemiology ; Female ; Heart Neoplasms/*mortality ; Humans ; Male ; Mesothelioma/*mortality ; Middle Aged ; Pericardium ; Peritoneal Neoplasms/*mortality ; Pleural Neoplasms/*mortality ; Young Adult ; }, abstract = {Mesothelioma mortality and its socio-demographic and temporal patterns in Argentina from 1980 to 2013 were estimated using data from death certificates obtained from the Vital Statistics System of Argentina's National Ministry of Health. There were 3,259 mesothelioma deaths corresponding to an age-adjusted mortality of 3.1/1,000,000 in 1980 and 5.7/1,000,000 in 2013, an average increase of 84.1% in 34 years. This raising trend became clearer after 1997. Males had higher mortality estimates compared with women in every year of the series; these findings suggest past exposure to asbestos. It is plausible that the asbestos exposure was mostly occupational, which is more common among men. Actions related to reinforcing the asbestos ban already in place and strengthening health surveillance directed at workplaces, previously exposed workers, and the population in general are recommended.}, } @article {pmid28558669, year = {2017}, author = {Johnen, G and Gawrych, K and Raiko, I and Casjens, S and Pesch, B and Weber, DG and Taeger, D and Lehnert, M and Kollmeier, J and Bauer, T and Musk, AW and Robinson, BWS and Brüning, T and Creaney, J}, title = {Calretinin as a blood-based biomarker for mesothelioma.}, journal = {BMC cancer}, volume = {17}, number = {1}, pages = {386}, pmid = {28558669}, issn = {1471-2407}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/toxicity ; Australia ; Biomarkers, Tumor/*blood ; Calbindin 2/*blood/genetics ; Germany ; Humans ; Lung Neoplasms/*blood/chemically induced/pathology ; Male ; Mesothelioma/*blood/chemically induced/pathology ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/*blood/pathology ; }, abstract = {BACKGROUND: Malignant mesothelioma (MM) is a deadly cancer mainly caused by previous exposure to asbestos. With a latency period up to 50 years the incidence of MM is still increasing, even in countries that banned asbestos. Secondary prevention has been established to provide persons at risk regular health examinations. An earlier detection with tumor markers might improve therapeutic options. Previously, we have developed a new blood-based assay for the protein marker calretinin. Aim of this study was the verification of the assay in an independent study population and comparison with the established marker mesothelin.

METHODS: For a case-control study in men, a total of 163 cases of pleural MM and 163 controls were available from Australia, another 36 cases and 72 controls were recruited in Germany. All controls had asbestosis and/or plaques. Calretinin and mesothelin were determined by ELISA (enzyme-linked immunosorbent assay) in serum or plasma collected prior to therapy. We estimated the performance of both markers and tested factors potentially influencing marker concentrations like age, sample storage time, and MM subtype.

RESULTS: Calretinin was able to detect all major subtypes except for sarcomatoid MM. Calretinin showed a similar performance in Australian and German men. At a pre-defined specificity of 95% the sensitivity of calretinin reached 71% and that of mesothelin 69%, when excluding sarcomatoid MM. At 97% specificity, the combination with calretinin increased the sensitivity of mesothelin from 66% to 75%. Sample storage time did not influence the results. In controls the concentrations of calretinin increased 1.87-fold (95% CI 1.10-3.20) per 10 years of age and slightly more for mesothelin (2.28, 95% CI 1.30-4.00).

CONCLUSIONS: Calretinin could be verified as a blood-based marker for MM. The assay is robust and shows a performance that is comparable to that of mesothelin. Retrospective analyses would not be limited by storage time. The high specificity supports a combination of calretinin with other markers. Calretinin is specific for epithelioid and biphasic MM but not the rarer sarcomatoid form. Molecular markers like calretinin and mesothelin are promising tools to improve and supplement the diagnosis of MM and warrant further validation in a prospective study.}, } @article {pmid28553954, year = {2017}, author = {Kato, T and Sato, T and Yokoi, K and Sekido, Y}, title = {E-cadherin expression is correlated with focal adhesion kinase inhibitor resistance in Merlin-negative malignant mesothelioma cells.}, journal = {Oncogene}, volume = {36}, number = {39}, pages = {5522-5531}, doi = {10.1038/onc.2017.147}, pmid = {28553954}, issn = {1476-5594}, mesh = {Antigens, CD ; Apoptosis/drug effects ; Cadherins/*biosynthesis ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Drug Resistance, Neoplasm ; Focal Adhesion Kinase 1/*antagonists & inhibitors ; Gene Expression ; Humans ; Lung Neoplasms/*drug therapy/*metabolism/pathology ; Mesothelioma/*drug therapy/*metabolism/pathology ; Mesothelioma, Malignant ; Neurofibromin 2/*deficiency/metabolism ; Protein Kinase Inhibitors/*pharmacology ; Signal Transduction ; }, abstract = {Malignant mesothelioma (MM) is an aggressive tumor commonly caused by asbestos exposure after a long latency. Focal adhesion kinase (FAK) inhibitors inhibit the cell growth of Merlin-deficient MM cells; however, their clinical efficacy has not been clearly determined. The aim of this study was to evaluate the growth inhibitory effect of the FAK inhibitor VS-4718 on MM cell lines and identify biomarkers for its efficacy. Although most Merlin-deficient cell lines were sensitive to VS-4718 compared with control MeT-5A cells, a subset of these cell lines exhibited resistance to this drug. Microarray and qRT-PCR analyses using RNA isolated from Merlin-deficient MM cell lines revealed a significant correlation between E-cadherin mRNA levels and VS-4718 resistance. Merlin- and E-cadherin-negative Y-MESO-22 cells underwent apoptosis upon treatment with a low concentration of VS-4718, whereas Merlin-negative, E-cadherin-positive Y-MESO-9 cells did not undergo VS-4718-induced apoptosis. Furthermore, E-cadherin knockdown in Merlin-negative MM cells significantly sensitized cells to VS-4718 and induced apoptotic cell death upon VS-4718 treatment. Together, our results suggest that E-cadherin serves as a predictive biomarker for molecular target therapy with FAK inhibitors for patients with mesothelioma and that its expression endows MM cells with resistance to FAK inhibitors.}, } @article {pmid28551647, year = {2017}, author = {Rizzardi, C and Athanasakis, E and Cammisuli, F and Monego, SD and DE Spelorzi, YCC and Costantinides, F and Giudici, F and Pinamonti, M and Canzonieri, V and Melato, M and Pascolo, L}, title = {Puzzling Results from BAP1 Germline Mutations Analysis in a Group of Asbestos-Exposed Patients in a High-risk Area of Northeast Italy.}, journal = {Anticancer research}, volume = {37}, number = {6}, pages = {3073-3083}, doi = {10.21873/anticanres.11663}, pmid = {28551647}, issn = {1791-7530}, mesh = {Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Environmental Exposure/adverse effects ; Female ; Germ-Line Mutation ; Humans ; Italy ; Lung Neoplasms/etiology/*genetics ; Male ; Mesothelioma/etiology/*genetics ; Mesothelioma, Malignant ; Middle Aged ; Risk ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {BACKGROUND: Germline mutations of the oncosuppressor gene breast cancer 1-associated protein 1 (BAP1) were recently related to an autosomal-dominant tumor predisposition syndrome (BAP1-TPDS), characterized by uveal melanoma, malignant mesothelioma (MM), cutaneous melanoma, and other malignancies. The demonstration that BAP1 mutations are strongly associated with MM has provided a real breakthrough in the study of genetic predisposition in MM, that may explain why only a fraction of asbestos-exposed individuals go on to develop MM.

MATERIALS AND METHODS: To evaluate the possible role of BAP1 mutations in the epidemiology of sporadic MM, and their relationship with asbestos exposure, we determined the prevalence of germline BAP1 mutations by the Sanger method in a group of 29 asbestos-exposed patients, 21 of which were diagnosed with MM. They were residents of Trieste, a ship-building town in Northeast Italy with a very high incidence of mesothelioma.

RESULTS: We identified non-obviously pathogenetic germline sequence variants of BAP1 in 3/29 patients and in 2/21 MM cases (10%).

CONCLUSION: Non obviously pathogenic germline sequence variants of BAP1 were found. Nevertheless, limitations of predictive web tools allowed us to comment on some interesting peculiarities of our findings.}, } @article {pmid28534416, year = {2017}, author = {Xu, R and Mesaros, C and Weng, L and Snyder, NW and Vachani, A and Blair, IA and Hwang, WT}, title = {Comparison of statistical methods for detection of serum lipid biomarkers for mesothelioma and asbestos exposure.}, journal = {Biomarkers in medicine}, volume = {11}, number = {7}, pages = {547-556}, pmid = {28534416}, issn = {1752-0371}, support = {P30 ES013508/ES/NIEHS NIH HHS/United States ; P42 ES023720/ES/NIEHS NIH HHS/United States ; P30 CA016520/CA/NCI NIH HHS/United States ; T32 ES019851/ES/NIEHS NIH HHS/United States ; R03 CA211820/CA/NCI NIH HHS/United States ; K22 ES026235/ES/NIEHS NIH HHS/United States ; }, mesh = {Asbestos/*adverse effects ; Biomarkers, Tumor/*blood ; Blood Chemical Analysis/*methods ; Case-Control Studies ; Environmental Exposure/*adverse effects ; Humans ; Lipids/*blood ; Mesothelioma/*blood ; Statistics as Topic/*methods ; }, abstract = {AIM: We compared three statistical methods in selecting a panel of serum lipid biomarkers for mesothelioma and asbestos exposure.

MATERIALS & METHODS: Serum samples from mesothelioma, asbestos-exposed subjects and controls (40 per group) were analyzed. Three variable selection methods were considered: top-ranked predictors from univariate model, stepwise and least absolute shrinkage and selection operator. Crossed-validated area under the receiver operating characteristic curve was used to compare the prediction performance.

RESULTS: Lipids with high crossed-validated area under the curve were identified. Lipid with mass-to-charge ratio of 372.31 was selected by all three methods comparing mesothelioma versus control. Lipids with mass-to-charge ratio of 1464.80 and 329.21 were selected by two models for asbestos exposure versus control.

CONCLUSION: Different methods selected a similar set of serum lipids. Combining candidate biomarkers can improve prediction.}, } @article {pmid28527639, year = {2017}, author = {Mezei, G and Chang, ET and Mowat, FS and Moolgavkar, SH}, title = {Epidemiology of mesothelioma of the pericardium and tunica vaginalis testis.}, journal = {Annals of epidemiology}, volume = {27}, number = {5}, pages = {348-359.e11}, doi = {10.1016/j.annepidem.2017.04.001}, pmid = {28527639}, issn = {1873-2585}, mesh = {Asbestos/*toxicity ; Female ; Heart Neoplasms/pathology ; Humans ; Male ; Mesothelioma/*pathology ; Middle Aged ; Occupational Diseases ; Pericardium/*pathology ; Registries ; Testicular Neoplasms/*pathology ; Testis/*pathology ; United States ; }, abstract = {PURPOSE: Malignant mesothelioma most commonly arises in the pleura and peritoneum but also occurs rarely at other anatomical sites with mesothelial tissue, namely, the pericardium and tunica vaginalis testis (TVT). This review provides a better understanding of the epidemiology of mesothelioma of these extrapleural sites.

METHODS: We conducted a systematic review of the epidemiologic and clinical literature on pericardial mesothelioma and mesothelioma of the TVT. We also analyzed U.S. Surveillance, Epidemiology, and End Results cancer registry data to describe incidence patterns of these malignancies.

RESULTS: An etiologic role of asbestos exposure has been hypothesized for pericardial and TVT mesotheliomas, but no analytical case-control epidemiologic studies exist to test this relationship. A substantial proportion of cases with these malignancies report no known asbestos exposure. In large occupational cohorts with heavy asbestos exposures, no cases of pericardial or TVT mesothelioma have been reported. Trends in the incidence of these malignancies do not match those of pleural mesothelioma, which correspond to historical trends of commercial asbestos use. A male preponderance of pericardial mesothelioma is not evident.

CONCLUSIONS: In the absence of analytic epidemiologic studies, the etiologic role of environmental risk factors for mesothelioma of the pericardium and TVT remains elusive.}, } @article {pmid28523158, year = {2017}, author = {D'Agostin, F and De Michieli, P and Chermaz, C and Negro, C}, title = {Pleural and peritoneal mesotheliomas in the Friuli Venezia Giulia register: data analysis from 1995 to 2015 in Northeastern Italy.}, journal = {Journal of thoracic disease}, volume = {9}, number = {4}, pages = {1032-1045}, pmid = {28523158}, issn = {2072-1439}, abstract = {BACKGROUND: The Friuli Venezia Giulia Mesothelioma Register contains a case-list of 1,109 mesotheliomas (1,034 pleural, 75 peritoneal) during 1995-2015. Exposure data are available for almost all cases. The aim was to assess mesothelioma incidence in the Region, an area with several shipyards, and to investigate determinants of mesothelioma latency among occupational cases.

METHODS: Incidence rates were calculated. Univariate and multivariate analyses were performed to estimate latency time by anatomical site, gender, diagnostic period and industry sector.

RESULTS: Mesothelioma incidence rates among men were higher than among women during the overall period. The incidence of pleural mesothelioma in men leveled off until 2009 (6.50 per 100,000) with a slight decrease thereafter. For women, the rate increased until 2006 (1.31 per 100,000) and then remained relatively stable. The incidence of peritoneal mesothelioma in men was constant whereas rate among women increased during 2010-2015. The number of cases diagnosed during three-year periods remained level. In multivariate model, site and gender were not relevant for latency period whereas construction workers had a shorter latency than shipyard workers.

CONCLUSIONS: Despite the asbestos ban since 1992, occupational exposure is still at risk. This highlights the need to assess exposure levels and to find a reliable health surveillance tool.}, } @article {pmid28505004, year = {2017}, author = {Desmeules, P and Joubert, P and Zhang, L and Al-Ahmadie, HA and Fletcher, CD and Vakiani, E and Delair, DF and Rekhtman, N and Ladanyi, M and Travis, WD and Antonescu, CR}, title = {A Subset of Malignant Mesotheliomas in Young Adults Are Associated With Recurrent EWSR1/FUS-ATF1 Fusions.}, journal = {The American journal of surgical pathology}, volume = {41}, number = {7}, pages = {980-988}, pmid = {28505004}, issn = {1532-0979}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; P50 CA140146/CA/NCI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Biomarkers, Tumor/*genetics ; Child ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Lung Neoplasms/*genetics/pathology ; Male ; Mesothelioma/*genetics/pathology ; Mesothelioma, Malignant ; *Oncogene Fusion ; Oncogene Proteins, Fusion/*genetics ; Peritoneal Neoplasms/*genetics/pathology ; Pleural Neoplasms/*genetics/pathology ; RNA-Binding Protein FUS/*genetics ; Young Adult ; }, abstract = {Malignant mesothelioma (MM) is a rare, aggressive tumor often associated with asbestos exposure and characterized by complex genetic abnormalities, including deletions of chromosome 22. A gene fusion involving EWSR1 and YY1 gene on 14q32 has been reported in 2 patients over the age of 60 with peritoneal MM. However, the incidence of EWSR1 rearrangements in MM and the spectrum of its fusion partners remain unknown. We recently encountered 2 MM cases with EWSR1-ATF1 fusions and sought to investigate the prevalence and clinicopathologic features associated with this abnormality. As both index cases occurred as intra-abdominal tumors in young adults, we searched our files for pleural and peritoneal MM occurring in adults younger than age of 40. All cases were tested by fluorescence in situ hybridization using custom bacterial artificial chromosomes probes for EWSR1, FUS, and ATF1 genes. When available, immunohistochemistry for BAP1 was performed. A total of 25 MM from patients aged 40 or less were screened, either from peritoneum (n=13) or pleura (n=12), with a median age of 31 (range: 7 to 40 y). Two additional ATF1-rearranged tumors were identified at pleural and peritoneal sites with EWSR1 and FUS as fusion partners, respectively, for a total of 4 cases (16%, 4/25). The fusion-positive cases displayed classic epithelioid morphology, immunoreactivity for cytokeratins and WT1, and negativity for S100. BAP1 expression was retained in the 3 fusion-positive cases with available material, and in 80% (12/15) of the fusion-negative cases. Our results expand the spectrum of tumor types harboring EWSR1/FUS-ATF1 gene fusions to include a subgroup of conventional epithelioid MM. Other features of this unique MM subset include young age at presentation, lack of asbestos exposure and retained BAP1 expression.}, } @article {pmid28501798, year = {2017}, author = {Lacourt, A and Lévêque, E and Guichard, E and Gilg Soit Ilg, A and Sylvestre, MP and Leffondré, K}, title = {Dose-time-response association between occupational asbestos exposure and pleural mesothelioma.}, journal = {Occupational and environmental medicine}, volume = {74}, number = {9}, pages = {691-697}, doi = {10.1136/oemed-2016-104133}, pmid = {28501798}, issn = {1470-7926}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Case-Control Studies ; Dose-Response Relationship, Drug ; Female ; France ; Humans ; Logistic Models ; Lung Neoplasms/*etiology ; Male ; Mesothelioma/*etiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Diseases/*etiology ; Occupational Exposure/*adverse effects ; Odds Ratio ; Pleura/*drug effects/pathology ; Pleural Neoplasms/*etiology/pathology ; Risk Factors ; }, abstract = {OBJECTIVES: Early occupational exposure to asbestos has been shown to be associated with an increased risk of pleural mesothelioma (PM), which suggests that the timing of exposure might play a role in the dose-response relationship. However, none studies has evaluated the relative impact of increasing the annual intensity of occupational exposure to asbestos at each time of the whole exposure history. Yet such evaluation would allow the comparison of the risks of PM associated with different longitudinal profiles of occupational exposure to asbestos. Our objective was to estimate the time-dependent relative impact of asbestos exposure intensity over the whole occupational history and to compare the resulting estimated risks of PM associated with different profiles of exposure, using data from a large French case-control study.

METHODS: This study included 1196 male cases recruited in 1987-2006 and 2369 matched controls on birth year. Occupational exposure to asbestos was assessed using a job exposure matrix and represented in logistic regression models using a flexible weighted cumulative index of exposure.

RESULTS: Due to much stronger weights of early doses of asbestos exposure, subjects who accumulated 20 fibres/mL over their entire job history with high doses during the first years and low doses thereafter were at higher risk of PM than those who accumulated most of the doses later (OR=2.37 (95% CI 2.01 to 2.87)).

CONCLUSION: This study provides new insights on the dose-time-response relationship between occupational asbestos and PM and illustrates the importance of considering timing of exposure in its association with cancer risk.}, } @article {pmid28500034, year = {2017}, author = {Freitas, DMM and Ramos, RL and Serpa Pinto, L and Ribeiro, R}, title = {Primary pericardial mesothelioma and asbestos exposure: a rare fatal disease.}, journal = {BMJ case reports}, volume = {2017}, number = {}, pages = {}, pmid = {28500034}, issn = {1757-790X}, mesh = {Aged ; Disease Progression ; Environmental Exposure/*adverse effects ; Female ; Heart Diseases/*chemically induced ; Humans ; Lung Neoplasms/*chemically induced ; Mesothelioma/*chemically induced ; Mesothelioma, Malignant ; Pericardial Effusion/*chemically induced ; Pericardium ; Rare Diseases/*chemically induced ; }, } @article {pmid28498408, year = {2017}, author = {Maeda, M and Chen, Y and Lee, S and Kumagai-Takei, N and Yoshitome, K and Matsuzaki, H and Yamamoto, S and Hatayama, T and Ikeda, M and Nishimura, Y and Otsuki, T}, title = {Induction of IL-17 production from human peripheral blood CD4+ cells by asbestos exposure.}, journal = {International journal of oncology}, volume = {50}, number = {6}, pages = {2024-2032}, doi = {10.3892/ijo.2017.3991}, pmid = {28498408}, issn = {1791-2423}, mesh = {Asbestos/toxicity ; CD4-Positive T-Lymphocytes/drug effects/immunology ; Coculture Techniques ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Interferon-gamma/*genetics ; Interleukin-17/*genetics/immunology ; Ionomycin/administration & dosage ; Lung Neoplasms/chemically induced/*genetics/immunology/pathology ; Mesothelioma/chemically induced/*genetics/immunology/pathology ; Mesothelioma, Malignant ; Phorbol Esters/administration & dosage ; Receptors, Antigen, T-Cell/genetics ; Receptors, CXCR3/*genetics ; T-Lymphocytes, Cytotoxic/drug effects/immunology ; Th17 Cells/drug effects/immunology ; }, abstract = {We have previously reported that chronic, recurrent and low-dose exposure to asbestos fibers causes a reduction in antitumor immunity. Investigation of natural killer (NK) cells using an in vitro cell line model and comprising in vitro activation using freshly isolated NK cells co-cultured with chrysotile fibers, as well as NK cells derived from asbestos-exposed patients with pleural plaque (PP) or malignant mesothelioma (MM), revealed decreased expression of NK cell activating receptors such as NKG2D, 2B4 and NKp46. An in vitro differentiation and clonal expansion model for CD8+ cytotoxic T lymphocytes (CTLs) showed reduced cytotoxicity with decreased levels of cytotoxic molecules such as granzyme B and perforin, as well as suppressed proliferation of CTLs. Additionally, analysis of T helper cells showed that surface CXCR3, chemokine receptor, and the productive potential of interferon (IFN)γ were reduced following asbestos exposure in an in vitro cell line model and in peripheral CD4+ cells of asbestos-exposed patients. Moreover, experiments revealed that asbestos exposure enhanced regulatory T cell (Treg) function. This study also focused on CXCR3 expression and the Th-17 cell fraction. Following activation with T-cell receptor and co-culture with various concentrations of chrysotile fibers using freshly isolated CD4+ surface CXCR3 positive and negative fractions, the intracellular expression of CXCR3, IFNγ and IL-17 remained unchanged when co-cultured with chrysotile. However, subsequent re-stimulation with phorbol 12-myristate 13-acetate (PMA) and ionomycin resulted in enhanced IL-17 production and expression, particularly in CD4+ surface CXCR3 positive cells. These results indicated that the balance and polarization between Treg and Th-17 fractions play an important role with respect to the immunological effects of asbestos and the associated reduction in antitumor immunity.}, } @article {pmid28481375, year = {2017}, author = {D' Agostin, F and de Michieli, P and Negro, C}, title = {Pleural mesothelioma in household members of asbestos-exposed workers in Friuli Venezia Giulia, Italy.}, journal = {International journal of occupational medicine and environmental health}, volume = {30}, number = {3}, pages = {419-431}, doi = {10.13075/ijomeh.1896.00890}, pmid = {28481375}, issn = {1896-494X}, mesh = {Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Asbestosis/epidemiology/etiology ; Environmental Exposure/*adverse effects ; *Family Characteristics ; Female ; Humans ; Italy/epidemiology ; Lung Neoplasms/*epidemiology/etiology ; Male ; Mesothelioma/*epidemiology/etiology ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/*epidemiology/etiology ; Retrospective Studies ; }, abstract = {OBJECTIVES: Malignant mesothelioma is closely associated to asbestos exposure. One such exposure may occur through contact with occupationally exposed household members and their belongings. This study examines the features of pleural mesothelioma attributable only to asbestos brought home by another family member.

MATERIAL AND METHODS: The data sources were 1063 mesothelioma cases diagnosed between 1995 and 2014, from the Friuli Venezia Giulia Mesothelioma Register. In all cases the diagnosis of mesothelioma was based on the pathology report. Exposure information and demographic data were acquired by an occupational medical standardized questionnaire/interview.

RESULTS: Household-exposure mesothelioma cases included 33 women and 2 men. Relationships were: wives (N = 22), daughters (N = 9), sons (N = 2), and mothers (N = 2). Asbestos exposure in the workers predominantly occurred in shipyards. Out of the 35 pleural cases, 19 were epithelial, 9 biphasic, 3 sarcomatoid, and 4 not specified. The mean age at diagnosis was 77 years old. The mean latency was 59 years, with wives having a significant shorter latency than offspring. Latency was not significantly related to morphology and asbestosis. The overall mean survival was 16 months (median 11 months) but treatment was beneficial (mean 16 months vs. 7 months). Biphasic/sarcomatoid histology and presence of asbestosis were associated with a decreased survival, although not with statistical significance.

CONCLUSIONS: Our data confirms that household exposure increases the risk for pleural mesothelioma amongst women with no history of occupational asbestos exposure. This is an ongoing problem in many countries, as well as in Italy, where the evaluation of a framework for the compensation of these cases is under debate. Int J Occup Med Environ Health 2017;30(3):419-431.}, } @article {pmid28472171, year = {2017}, author = {Cavalleri, T and Angelici, L and Favero, C and Dioni, L and Mensi, C and Bareggi, C and Palleschi, A and Rimessi, A and Consonni, D and Bordini, L and Todaro, A and Bollati, V and Pesatori, AC}, title = {Plasmatic extracellular vesicle microRNAs in malignant pleural mesothelioma and asbestos-exposed subjects suggest a 2-miRNA signature as potential biomarker of disease.}, journal = {PloS one}, volume = {12}, number = {5}, pages = {e0176680}, pmid = {28472171}, issn = {1932-6203}, mesh = {Aged ; Asbestos/*toxicity ; Biomarkers, Tumor/*metabolism ; Female ; Humans ; Male ; Mesothelioma/chemically induced/*genetics ; MicroRNAs/*genetics ; Middle Aged ; Pleural Neoplasms/chemically induced/*genetics ; }, abstract = {BACKGROUND: Malignant Pleural Mesothelioma (MPM) is an aggressive cancer mainly caused by asbestos exposure and refractory to current therapies. Specific diagnostic markers for early MPM diagnosis are needed. Changes in miRNA expression have been implicated in several diseases and cancers, including MPM. We examined if a specific miRNA signature in plasmatic extracellular vesicles (EV) may help to discriminate between malignant pleural mesothelioma patients (MPM) and subjects with Past Asbestos Exposure (PAE).

We investigated 23 MPM patients and 19 cancer-free subjects with past asbestos exposure (PAE). We screened 754 miRNAs in plasmatic EVs by OpenArray and found 55 differential miRNAs using logistic regression models adjusted for age, sex, BMI, and smoking. Among the top-20 differential miRNAs chosen for validation by Real time PCR, 16 were confirmed. Using receiver operating characteristic (ROC) curve analysis, the most discriminating miRNA combination was given by miR-103a-3p + miR-30e-3p, which generated an AUC of 0.942 (95% CI 0.87-1.00), with a sensitivity of 95.5% and a specificity of 80.0%. Using multivariate Cox regression analysis including gender, age, BMI and smoking we found a Hazard Ratio for miR-103a-3p above the median of 0.37 (95%CI 0.13-1.13) and of 0.51 (95%CI 0.17-1.52) for miR-30e-3p.

CONCLUSIONS: This study suggests EV-associated miR-103a-3p and miR-30e-3p are able to discriminate MPM from PAE subjects. Larger and prospective studies are needed to confirm these two-miRNA signature alone or in combination with other biomarkers as diagnostic tools for MPM.}, } @article {pmid28446737, year = {2017}, author = {Barbieri, PG and Somigliana, AB and Lombardi, S and Festa, R and Girelli, R and Sarnico, M}, title = {[Pleural mesothelioma in doll manufacture: possible asbestos exposure].}, journal = {La Medicina del lavoro}, volume = {108}, number = {2}, pages = {111-117}, doi = {10.23749/mdl.v108i2.6115}, pmid = {28446737}, issn = {0025-7818}, mesh = {Aged ; Asbestos/*adverse effects ; *Carcinogens ; Female ; Humans ; *Industry ; Mesothelioma/*etiology ; Middle Aged ; Occupational Diseases/*etiology ; Occupational Exposure/*adverse effects ; Play and Playthings ; Pleural Neoplasms/*etiology ; }, abstract = {BACKGROUND: The occurrence of malignant mesothelioma is almost always causally associated to asbestos exposure but, considering women occurrences, this association is often difficult to demonstrate and consequently the asbestos exposure is defined as 'unknown'.

OBJECTIVES: To describe the working activity and to give occupational asbestos exposure probability estimation related to an uncommon and poorly investigated productive sector: doll manufacture.

METHODS: From the Province of Brescia Mesothelioma Registry, established in 1993 on population-based criteria, we have extracted the certified mesothelioma diagnosis cases, related to patients who were employed for some time in doll manufacture.

RESULTS: Among the 757 total cases of malignant mesothelioma registered and studied up to 2016, we found 3 cases of pleural epithelial mesothelioma histologically diagnosed in young women who had worked in two doll manufacturing companies and whose asbestos exposure had been initially defined as 'unknown', because an environmental, family or extra-professional asbestos exposure was considered unlikely. However, the judicial autopsy performed on one of the 3 women had allowed examining lung tissue samples with Scanning Electron Microscopy. This technique showed a concentration of amphiboles fibers of about 12,000,000 per gram of dry lung tissue, with a consequent re-classification of asbestos exposure from 'unknown' to 'occupational certified'.

DISCUSSION: Mesotheliomas in women with no apparent occupational asbestos exposure are normally referred to life or family environmental exposure. Moreover, it is known that occupational asbestos exposure in women is difficult to recognize. Previously, only one publication had reported two cases of mesothelioma in cloth doll manufacture. The occurrence of two mesothelioma cases in the same company out of the three here presented was suggesting an occupational exposure. The finding of a high amphibole fibers lung concentration confirmed the previous hypothesis, despite the impossibility to determine the circumstances with good evidence.

CONCLUSION: The three cases of mesothelioma in doll production workers suggest that also in this restricted manufacturing sector had occurred an occupational asbestos exposure, which is up to now unknown and isn't due only to the use of sewing or ironing machines. The lung asbestos fibers burden analysis is confirmed to be a decisive factor in the assessment of mesothelioma cases with 'unknown' exposure.}, } @article {pmid28438787, year = {2017}, author = {Pira, E and Romano, C and Donato, F and Pelucchi, C and Vecchia, C and Boffetta, P}, title = {Mortality from cancer and other causes among Italian chrysotile asbestos miners.}, journal = {Occupational and environmental medicine}, volume = {74}, number = {8}, pages = {558-563}, doi = {10.1136/oemed-2016-103673}, pmid = {28438787}, issn = {1470-7926}, mesh = {Aged ; Aged, 80 and over ; Asbestos, Serpentine/*adverse effects ; Cause of Death ; Chronic Disease/mortality ; Cohort Studies ; Environmental Monitoring ; Humans ; Italy/epidemiology ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; Mesothelioma, Malignant ; Middle Aged ; Mining ; Mortality ; Neoplasms/mortality ; Occupational Diseases/*mortality ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*mortality ; Poisson Distribution ; }, abstract = {OBJECTIVE: To investigate the long-term mortality of a cohort of Italian asbestos miners.

METHODS: The cohort included 1056 men employed in a chrysotile mine between 1930 and 1990, who were followed up during 1946-2014, for a total of 37 471 person-years of observation. Expected deaths and SMRs were computed using national and local (after 1980, when available) reference.

RESULTS: A total of 294 (27.8%) subjects were alive and at the end of follow-up, 722 (68.4%) were dead and 40 (3.8%) were lost to follow-up. The SMR for overall mortality was 1.35 (95%CI 1.25 to 1.45). The SMR for pleural cancer, based on seven observed deaths, was 5.54 (95% CI 2.22 to 11.4) and related to time since first exposure, but not to duration of employment, cumulative exposure or time since last exposure. The SMR for lung cancer was 1.16 (95% CI 0.87 to 1.52; 53 observed deaths), with no excess among workers with cumulative exposure below 100 fibre/mL-years (SMR 0.82; 95% CI 0.44 to 1.40).

CONCLUSIONS: The update of the follow-up of this cohort confirmed an increased mortality from pleural cancer mortality in miners exposed to chrysotile and a lack of significant increase in lung cancer mortality.}, } @article {pmid28435764, year = {2017}, author = {Bazine, A and Fetohi, M and Namad, T and Benzekri, A and Zainoun, B and Tanz, R and Ichou, M}, title = {A Case of Well-Differentiated Papillary Mesothelioma of the Male Peritoneum: Successful Treatment by Systemic Chemotherapy.}, journal = {Cureus}, volume = {9}, number = {3}, pages = {e1104}, pmid = {28435764}, issn = {2168-8184}, abstract = {Well-differentiated papillary mesothelioma of the peritoneum (WDPMP) is a rare subtype of epithelioid mesothelioma, which is usually seen in young women without a history of asbestos exposure, and generally, has an indolent course. The relative rarity of this neoplasm in males prompted us to report this case of a well-differentiated papillary mesothelioma of the peritoneum in a 36-year-old man. The patient, who had no history of asbestos exposure, presented with abdominal pain and ascites of unknown etiology. Computed tomography showed abundant ascites with nodules of the peritoneal cavity. Laparoscopic examination revealed a large number of white miliary nodules diffusely covering the peritoneum. Pathology revealed a diagnosis of well-differentiated papillary mesothelioma of the peritoneum, based on histomorphology and immunohistochemistry. The patient started chemotherapy with cisplatin and pemetrexed. After six cycles of chemotherapy, the effectiveness of this chemotherapy was checked by only the computed tomography. PET scan was not used because it is not routinely recommended in WDPMP. Few data are currently available in the literature regarding the performance of the PET scan in WDPMP. Nine months later, the patient was free of symptoms. Based on reviewing the literature and our observations in this case, consultation of other pathologists is highly recommended to discern WDPMP from other disseminated peritoneal diseases, in order to offer the most effective and safe therapeutic strategy. Chemotherapy should be strongly considered if the tumor is unresectable and accompanied by symptoms. Cisplatin and pemetrexed chemotherapy could be a promising therapeutic choice.}, } @article {pmid28412495, year = {2017}, author = {Liu, B and van Gerwen, M and Bonassi, S and Taioli, E and , }, title = {Epidemiology of Environmental Exposure and Malignant Mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {12}, number = {7}, pages = {1031-1045}, doi = {10.1016/j.jtho.2017.04.002}, pmid = {28412495}, issn = {1556-1380}, mesh = {Asbestos/*adverse effects ; Environmental Exposure/*adverse effects ; Female ; Humans ; Lung Neoplasms/*epidemiology/pathology ; Male ; Mesothelioma/*epidemiology/pathology ; Mesothelioma, Malignant ; }, abstract = {Although the association between exposure to asbestos and malignant mesothelioma (particularly malignant pleural mesothelioma) has been well established, the health impact of environmental exposure (EE) to asbestos has been less studied. This review summarizes the most recent studies on the association between malignant mesothelioma and EE with asbestos to identify features associated with EE and quantify the association with malignant mesothelioma. There were 44 studies from 18 countries that met our selection criteria, with a considerable amount of heterogeneity in their study design, measures of exposure, and health outcomes. The male-to-female ratio was close to or less than 1 and generally lower than the ratio reported when both occupational and environmental exposures were considered. Although recent studies have continued to improve our understanding of environmental exposure to asbestos, challenges remain. We have highlighted a few new research directions, such as a need for reliable matrices to identify common and less recognized types of EE, asbestos biomarker studies specifically focusing on EE, and research on populations and geographic areas that have not been previously studied.}, } @article {pmid28409856, year = {2017}, author = {Mensi, C and Ciullo, F and Barbieri, GP and Riboldi, L and Somigliana, A and Rasperini, G and Pesatori, AC and Consonni, D}, title = {Pleural malignant mesothelioma in dental laboratory technicians: A case series.}, journal = {American journal of industrial medicine}, volume = {60}, number = {5}, pages = {443-448}, doi = {10.1002/ajim.22716}, pmid = {28409856}, issn = {1097-0274}, mesh = {Aged ; Asbestos/*adverse effects ; Dental Casting Technique ; Dentistry ; Female ; Humans ; Italy ; Laboratory Personnel ; Lung Neoplasms/*chemically induced/diagnostic imaging ; Male ; Mesothelioma/*chemically induced/diagnostic imaging ; Mesothelioma, Malignant ; Middle Aged ; Occupational Diseases/*chemically induced/diagnostic imaging ; Occupational Exposure/*adverse effects ; Registries ; Surveys and Questionnaires ; }, abstract = {Asbestos was used in dentistry as a binder in periodontal dressings and as lining material for casting rings and crucible. However, until now, only one case of malignant mesothelioma with occupational exposure to asbestos in dental practice has been reported. We present 4 pleural mesotheliomas out of 5344 cases identified in Lombardy, Italy, in 2000-2014. Three men had been working as dental laboratory technicians, with asbestos exposure for 10, 34, and 4 years, and one woman had been helping her husband for 30 years in manufacturing dental prostheses. The men described the use of asbestos as a lining material for casting rings, while the woman was not able to confirm this use. We confirm the association of malignant mesothelioma with dental technician work. Dental technicians suffering from mesothelioma should be questioned about past occupational asbestos exposure.}, } @article {pmid28399779, year = {2017}, author = {Domen, A and De Laet, C and Vanderbruggen, W and Gielis, J and Hendriks, JM and Lauwers, P and Janssens, A and Hiddinga, B and Van Meerbeeck, JP and Van Schil, PE}, title = {Malignant pleural mesothelioma: single-institution experience of 101 patients over a 15-year period.}, journal = {Acta chirurgica Belgica}, volume = {117}, number = {3}, pages = {157-163}, doi = {10.1080/00015458.2016.1272253}, pmid = {28399779}, issn = {0001-5458}, mesh = {Adult ; Aged ; Aged, 80 and over ; Belgium ; Combined Modality Therapy ; Female ; Humans ; Lung Neoplasms/mortality/*pathology/therapy ; Male ; Mesothelioma/mortality/*pathology/therapy ; Mesothelioma, Malignant ; Middle Aged ; Neoplasm Staging ; Retrospective Studies ; Survival Rate ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare but aggressive neoplasm that typically originates from the mesothelial surfaces of the pleural cavity. Exposure to asbestos is the principal etiological agent of MPM. The disease is characterized by difficult stage classification and limited consensus on therapeutic approach. We have evaluated the experience with MPM in the Antwerp University Hospital over the past 15 years.

METHODS: A database was created with all patients diagnosed with or treated for a MPM between 2001 and 2015. A total of 101 patients were included on which different survival analyses were performed combined with a reproduction of demographic, clinical, histologic and therapeutic data, and these were compared to literature data.

RESULTS: Vast majority of our 101 patients were male (80%) with a median age of 66 years at diagnosis with predominantly epitheloid histology (81%). Overall median survival was 18.3 months and overall 1-, 2- and 5-year survival rates were 68%, 37% and 7%, respectively. Kaplan-Meier analysis showed a non-significant difference in survival between the several best (b) TNM-stages (p = .356). A significant difference in survival was observed in patients undergoing surgery versus no surgery (p = .008), between the different histological types (p < .0001) and treatment with chemotherapy alone versus chemotherapy with surgery (p < .0001). Smoking at diagnosis and epitheloid histology have been identified as significant prognostic factors in the multivariate Cox regression model (HR 3.13 and 0.53, respectively).

CONCLUSION: Descriptive and survival analysis of our patient database confirmed the limitations of the current staging system and were concordant with literature regarding MPM.}, } @article {pmid28395242, year = {2017}, author = {Rapisarda, V and Caltabiano, R and Musumeci, G and Castrogiovanni, P and Ferrante, M and Ledda, C and Lombardo, C and Graziano, ACE and Cardile, V and Loreto, C}, title = {Analysis of fibulin-3 after exposure to asbestos-like fibers.}, journal = {Environmental research}, volume = {156}, number = {}, pages = {381-387}, doi = {10.1016/j.envres.2017.03.055}, pmid = {28395242}, issn = {1096-0953}, mesh = {Air Pollutants/toxicity ; Animals ; Asbestos, Amphibole/*toxicity ; Biomarkers/*blood ; Calcium-Binding Proteins/*genetics/metabolism ; Disease Models, Animal ; Female ; Fibroblasts/*drug effects ; Gene Expression/*drug effects ; Humans ; Immunohistochemistry ; Italy ; Lung/*drug effects ; Male ; Sheep ; }, abstract = {A significantly increased incidence of malignant mesothelioma in Biancavilla (Sicily, Italy) has been ascribed to exposure to fluoro-edenite, a fibrous amphibole extracted from a local stone quarry. Fibulin-3 is a highly conserved glycoprotein proposed as a biomarker for malignant mesothelioma that belongs to the family of extracellular matrix proteins. Previous studies demonstrated high Fibulin-3 plasma levels in workers with pleural plaques exposed to fluoro-edenite. Therefore, in order to gain insight into the biomolecular mechanisms of fluoro-edenite toxicity, we performed the analysis of Fibulin-3 expression by immunohistochemistry in the lung samples derived from sheep belonging to the area of Biancavilla. Furthermore, an in vitro model of exposed fluoro-edenite fibroblasts was used to perform functional experiments to better understand the modulation of Fibulin-3 expression. The percentage of immunostained area by Fibulin-3 was very much higher in exposed lungs compared with non-exposed ones. The Fibulin-3 protein level was significantly expressed in primary human lung fibroblasts exposed to 50 and 100µg/ml of fluoro-edenite fibers for 72h, compared to the unexposed controls. The results from the present study further demonstrate the implication of Fibulin-3 during fluoro-edenite exposure. This would endorse our previous results regarding the use of Fibulin-3 as a possible screening biomarker for fluoro-edenite exposed individuals, thereby contributing to the monitoring of the population at risk. The present study also suggested that the Fibulin-3 overexpression may reflect a defensive response of the tissues after exogenous stimuli and may be implicated in cancer development, especially in the context of fluoro-edenite contamination. However, further studies are necessary in order to make Fibulin-3 a customized screening tool.}, } @article {pmid28387650, year = {2017}, author = {Creaney, J and Dick, IM and Leon, JS and Robinson, BW}, title = {A Proteomic Analysis of the Malignant Mesothelioma Secretome Using iTRAQ.}, journal = {Cancer genomics & proteomics}, volume = {14}, number = {2}, pages = {103-117}, pmid = {28387650}, issn = {1790-6245}, mesh = {Aged ; Cell Line, Tumor ; Cells, Cultured ; Cluster Analysis ; Exosomes/genetics/metabolism ; Female ; Gene Ontology ; Humans ; Isotope Labeling/*methods ; Lung Neoplasms/metabolism/pathology ; Male ; Mass Spectrometry/*methods ; Mesothelioma/metabolism/pathology ; Mesothelioma, Malignant ; Middle Aged ; Principal Component Analysis ; Proteome/classification/genetics/*metabolism ; Proteomics/*methods ; }, abstract = {UNLABELLED: Backgound/Aim: Malignant mesothelioma (MM) is an aggressive and fatal pleural cancer. The cell secretome offers information allowing insight into the pathogenesis of MM while offering the possibility to identify potential therapeutic targets and biomarkers. In the present study the secretome protein profile of MM cell lines was compared to normal mesothelial cells.

MATERIALS AND METHODS: Six MM cell lines were compared against three primary mesothelial cell culture preparations using iTRAQ® mass spectrometry.

RESULTS: MM cell lines more abundantly secreted exosome-associated proteins than mesothelial cells. MM cell secretomes were enriched in proteins that are involved in response to stress, carbon metabolism, biosynthesis of amino acids, antigen processing and presentation and protein processing in the endoplasmic reticulum.

CONCLUSION: The MM cell secretome is enriched in proteins that are likely to enhance its growth and response to stress and help it inhibit an adaptive immune response. These are potential targets for therapeutic and biomarker discovery.}, } @article {pmid28377727, year = {2017}, author = {Rouka, E and Vavougios, GD and Solenov, EI and Gourgoulianis, KI and Hatzoglou, C and Zarogiannis, SG}, title = {Transcriptomic Analysis of the Claudin Interactome in Malignant Pleural Mesothelioma: Evaluation of the Effect of Disease Phenotype, Asbestos Exposure, and CDKN2A Deletion Status.}, journal = {Frontiers in physiology}, volume = {8}, number = {}, pages = {156}, pmid = {28377727}, issn = {1664-042X}, abstract = {Malignant pleural mesothelioma (MPM) is a highly aggressive tumor primarily associated with asbestos exposure. Early detection of MPM is restricted by the long latency period until clinical presentation, the ineffectiveness of imaging techniques in early stage detection and the lack of non-invasive biomarkers with high sensitivity and specificity. In this study we used transcriptome data mining in order to determine which CLAUDIN (CLDN) genes are differentially expressed in MPM as compared to controls. Using the same approach we identified the interactome of the differentially expressed CLDN genes and assessed their expression profile. Subsequently, we evaluated the effect of tumor histology, asbestos exposure, CDKN2A deletion status, and gender on the gene expression level of the claudin interactome. We found that 5 out of 15 studied CLDNs (4, 5, 8, 10, 15) and 4 out of 27 available interactors (S100B, SHBG, CDH5, CXCL8) were differentially expressed in MPM specimens vs. healthy tissues. The genes encoding the CLDN-15 and S100B proteins present differences in their expression profile between the three histological subtypes of MPM. Moreover, CLDN-15 is significantly under-expressed in the cohort of patients with previous history of asbestos exposure. CLDN-15 was also found significantly underexpressed in patients lacking the CDKN2A gene. These results warrant the detailed in vitro investigation of the role of CDLN-15 in the pathobiology of MPM.}, } @article {pmid28361969, year = {2017}, author = {Tsuji, S and Washimi, K and Kageyama, T and Yamashita, M and Yoshihara, M and Matsuura, R and Yokose, T and Kameda, Y and Hayashi, H and Morohoshi, T and Tsuura, Y and Yusa, T and Sato, T and Togayachi, A and Narimatsu, H and Nagasaki, T and Nakamoto, K and Moriwaki, Y and Misawa, H and Hiroshima, K and Miyagi, Y and Imai, K}, title = {HEG1 is a novel mucin-like membrane protein that serves as a diagnostic and therapeutic target for malignant mesothelioma.}, journal = {Scientific reports}, volume = {7}, number = {}, pages = {45768}, pmid = {28361969}, issn = {2045-2322}, mesh = {Antibodies, Monoclonal/*immunology/metabolism ; Biomarkers, Tumor/immunology/metabolism ; Cell Line, Tumor ; Cell Proliferation ; Glycosylation ; Humans ; Lung Neoplasms/*diagnosis/*immunology/metabolism ; Membrane Proteins/genetics/*immunology/metabolism ; Mesothelioma/*diagnosis/*immunology/metabolism ; Mesothelioma, Malignant ; Sensitivity and Specificity ; }, abstract = {The absence of highly specific markers for malignant mesothelioma (MM) has served an obstacle for its diagnosis and development of molecular-targeting therapy against MM. Here, we show that a novel mucin-like membrane protein, sialylated protein HEG homolog 1 (HEG1), is a highly specific marker for MM. A monoclonal antibody against sialylated HEG1, SKM9-2, can detect even sarcomatoid and desmoplastic MM. The specificity and sensitivity of SKM9-2 to MM reached 99% and 92%, respectively; this antibody did not react with normal tissues. This accurate discrimination by SKM9-2 was due to the recognition of a sialylated O-linked glycan with HEG1 peptide. We also found that gene silencing of HEG1 significantly suppressed the survival and proliferation of mesothelioma cells; this result suggests that HEG1 may be a worthwhile target for function-inhibition drugs. Taken together, our results indicate that sialylated HEG1 may be useful as a diagnostic and therapeutic target for MM.}, } @article {pmid28351431, year = {2017}, author = {Mensi, C and Romano, A and Berti, A and Dore, R and Riboldi, L}, title = {A second case of pericardial mesothelioma mimicking systemic lupus erythematosus in the literature in over 30 years: a case report.}, journal = {Journal of medical case reports}, volume = {11}, number = {1}, pages = {85}, pmid = {28351431}, issn = {1752-1947}, mesh = {Diagnosis, Differential ; Echocardiography ; Fatal Outcome ; Female ; Heart Neoplasms/*diagnosis/pathology ; Humans ; Lupus Erythematosus, Systemic/*diagnosis ; Mesothelioma/complications/*diagnosis/pathology ; Middle Aged ; Pericardial Effusion/etiology/therapy ; Pericardiocentesis ; *Pericardium/diagnostic imaging ; Radiography ; Time Factors ; Tomography, X-Ray Computed ; }, abstract = {BACKGROUND: Mesothelioma is a rare neoplasm which commonly develops in the pleura of people exposed to asbestos. Pericardial mesothelioma accounts for only 0.7 % of all malignant mesotheliomas and it usually presents with pericardial effusion, mimicking serositis. To date, there are approximately 200 cases of pericardial mesothelioma described in the medical literature, and little knowledge exists about the systemic manifestations of this pathology. The first and only described case of pericardial mesothelioma with autoimmune features dates back to 1984 and, in our case report, we describe the second.

CASE PRESENTATION: We report a case of a 45-year-old white woman whose pericardial mesothelioma was initially misdiagnosed as pericardial involvement of an autoimmune disease (systemic lupus erythematosus). After several relapses of pericardial effusion, a computed tomography scan and a biopsy with histological analysis were performed revealing neoplastic growth.

CONCLUSIONS: We describe a rare case of pericardial mesothelioma in a patient with a clinical presentation compatible with lupus serositis. Clinicians should consider malignant mesothelioma in the differential diagnosis of pericardial effusion, especially when it is recurrent and not clearly explained by other causes. Cytological samples should always be obtained and, if imaging tools are suggestive for solid processes, histological confirmation is mandatory.}, } @article {pmid28348451, year = {2017}, author = {Ying, S and Jiang, Z and He, X and Yu, M and Chen, R and Chen, J and Ru, G and Chen, Y and Chen, W and Zhu, L and Li, T and Zhang, Y and Guo, X and Yin, X and Zhang, X and Lou, J}, title = {Serum HMGB1 as a Potential Biomarker for Patients with Asbestos-Related Diseases.}, journal = {Disease markers}, volume = {2017}, number = {}, pages = {5756102}, pmid = {28348451}, issn = {1875-8630}, mesh = {Aged ; Asbestosis/*blood ; Biomarkers, Tumor/*blood ; Case-Control Studies ; Female ; HMGB1 Protein/*blood ; Humans ; Lung Neoplasms/*blood ; Male ; Matrix Metalloproteinase 2/blood ; Matrix Metalloproteinase 9/blood ; Mesothelioma/*blood ; Mesothelioma, Malignant ; Middle Aged ; }, abstract = {High-mobility group box 1 (HMGB1) functions as a proinflammatory cytokine and is one of the most intriguing molecules in inflammatory disorders and cancers. Notably, HMGB1 is a potential therapeutic target and novel biomarker in related diseases. However, the diagnostic value of HMGB1 for benign and malignant asbestos-related diseases (ARDs) remains unclear. In this work, we detected preoperative serum HMGB1 levels in Chinese asbestos-exposed (AE) and ARDs populations and further evaluated the diagnostic value of HMGB1 in patients with certain types of ARDs, including those with pleural plaques, asbestosis, or malignant mesothelioma (MM). The experimental data presented that the serum level of HMGB1 was significantly elevated in AE and ARDs subjects. Our findings indicated that serum HMGB1 is a sensitive and specific biomarker for discriminating asbestosis- and MM-affected individuals from healthy or AE individuals. In addition, serum matrix metalloproteinases 2 and 9 are not correlated with HMGB1 in ARDs. Thus, our study provides supporting evidence for HMGB1 as a potential biomarker either for the clinical diagnosis of high-risk AE cohorts or for evaluating ARDs.}, } @article {pmid28348450, year = {2017}, author = {Bonotti, A and Foddis, R and Landi, S and Melaiu, O and De Santi, C and Giusti, L and Donadio, E and Ciregia, F and Mazzoni, MR and Lucacchini, A and Bovenzi, M and Comar, M and Pantani, E and Pistelli, A and Cristaudo, A}, title = {A Novel Panel of Serum Biomarkers for MPM Diagnosis.}, journal = {Disease markers}, volume = {2017}, number = {}, pages = {3510984}, pmid = {28348450}, issn = {1875-8630}, mesh = {Aged ; Biomarkers, Tumor/*blood ; Blood Proteins/metabolism ; Case-Control Studies ; Female ; Humans ; Lung Neoplasms/*blood ; Male ; Mesothelioma/*blood ; Mesothelioma, Malignant ; Middle Aged ; Proteome/metabolism ; }, abstract = {Exposure to asbestos is the main cause of malignant pleural mesothelioma (MPM), a highly aggressive cancer of the pleura. Since the only tools for early detection are based on radiological tests, some authors focused on serum markers (i.e., mesothelin). The aim of this study was the evaluation of new serum biomarkers to be used individually or in combination, in order to improve the outcome of patients whose disease would be diagnosed at an earlier stage. Serum and plasma were available from 43 subjects previously exposed to asbestos and 27 MPM patients, all being epithelioid type. All the new markers found differentially expressed in MPM and healthy subjects, by proteomic and genomic approaches, have been validated in the serum by the use of specific ELISA. The combined approach, using tools of genomics and proteomics, is found to be highly innovative for this type of disease and led to the identification of new serum markers in the diagnosis of MPM. These results, if confirmed in a larger series, may have a strong impact in this area, because early detection of this cancer in people at high risk could significantly improve the course of the disease and the clinical approach to an individualized therapy.}, } @article {pmid28344849, year = {2017}, author = {Choi, S and Kang, D and Park, D and Lee, H and Choi, B}, title = {Developing Asbestos Job Exposure Matrix Using Occupation and Industry Specific Exposure Data (1984-2008) in Republic of Korea.}, journal = {Safety and health at work}, volume = {8}, number = {1}, pages = {105-115}, pmid = {28344849}, issn = {2093-7911}, abstract = {BACKGROUND: The goal of this study is to develop a general population job-exposure matrix (GPJEM) on asbestos to estimate occupational asbestos exposure levels in the Republic of Korea.

METHODS: Three Korean domestic quantitative exposure datasets collected from 1984 to 2008 were used to build the GPJEM. Exposure groups in collected data were reclassified based on the current Korean Standard Industrial Classification (9[th] edition) and the Korean Standard Classification of Occupations code (6[th] edition) that is in accordance to international standards. All of the exposure levels were expressed by weighted arithmetic mean (WAM) and minimum and maximum concentrations.

RESULTS: Based on the established GPJEM, the 112 exposure groups could be reclassified into 86 industries and 74 occupations. In the 1980s, the highest exposure levels were estimated in "knitting and weaving machine operators" with a WAM concentration of 7.48 fibers/mL (f/mL); in the 1990s, "plastic products production machine operators" with 5.12 f/mL, and in the 2000s "detergents production machine operators" handling talc containing asbestos with 2.45 f/mL. Of the 112 exposure groups, 44 groups had higher WAM concentrations than the Korean occupational exposure limit of 0.1 f/mL.

CONCLUSION: The newly constructed GPJEM which is generated from actual domestic quantitative exposure data could be useful in evaluating historical exposure levels to asbestos and could contribute to improved prediction of asbestos-related diseases among Koreans.}, } @article {pmid28343162, year = {2017}, author = {De Santi, C and Pucci, P and Bonotti, A and Melaiu, O and Cipollini, M and Silvestri, R and Vymetalkova, V and Barone, E and Paolicchi, E and Corrado, A and Lepori, I and Dell'Anno, I and Pellè, L and Vodicka, P and Mutti, L and Foddis, R and Cristaudo, A and Gemignani, F and Landi, S}, title = {Mesothelin promoter variants are associated with increased soluble mesothelin-related peptide levels in asbestos-exposed individuals.}, journal = {Occupational and environmental medicine}, volume = {74}, number = {6}, pages = {456-463}, doi = {10.1136/oemed-2016-104024}, pmid = {28343162}, issn = {1470-7926}, mesh = {Aged ; Alleles ; Analysis of Variance ; Asbestos/adverse effects ; Biomarkers, Tumor/blood/*genetics ; Female ; GPI-Linked Proteins/*blood/*genetics ; Genotype ; Humans ; Italy ; Luciferases ; Lung Neoplasms/blood/*diagnosis/*genetics ; Male ; Mesothelin ; Mesothelioma/blood/*diagnosis/*genetics ; Mesothelioma, Malignant ; Middle Aged ; Polymorphism, Single Nucleotide ; Sensitivity and Specificity ; }, abstract = {BACKGROUND: Soluble mesothelin-related peptide (SMRP) is a promising diagnostic biomarker for malignant pleural mesothelioma (MPM), but various confounders hinder its usefulness in surveillance programmes. We previously showed that a single nucleotide polymorphism (SNP) within the 3'untranslated region (3'UTR) of the mesothelin (MSLN) gene could affect the levels of SMRP.

OBJECTIVES: To focus on SNPs located within MSLN promoter as possible critical genetic variables in determining SMRP levels.

METHODS: The association between SMRP and SNPs was tested in 689 non-MPM subjects and 70 patients with MPM. Reporter plasmids carrying the four most common haplotypes were compared in a dual luciferase assay, and in silico analyses were performed to investigate the putative biological role of the SNPs.

RESULTS: We found a strong association between serum SMRP and variant alleles of rs3764247, rs3764246 (in strong linkage disequilibrium with rs2235504) and rs2235503 in non-MPM subjects. Inclusion of the genotype information led to an increase in SMRP specificity from 79.9% to 85.5%. Although not statistically significant, the group with MPM showed the same trend of association. According to the in vitro luciferase study, rs3764247 itself had a functional role. In silico approaches showed that the binding sites for transcription factors such as Staf and ZNF143 could be affected by this SNP. The other SNPs were shown to interact with each other in a more complex way.

CONCLUSIONS: These data support the suggestion that SMRP performance is affected by individual (ie, genetic) variables and that MSLN expression is influenced by SNPs located within the promoter regulatory region.}, } @article {pmid28337371, year = {2017}, author = {Huang, L and Cai, M and Zhang, X and Wang, F and Chen, L and Xu, M and Yang, K and Chen, Z and Wang, X and Fu, L}, title = {Combinational therapy of crizotinib and afatinib for malignant pleural mesothelioma.}, journal = {American journal of cancer research}, volume = {7}, number = {2}, pages = {203-217}, pmid = {28337371}, issn = {2156-6976}, abstract = {Malignant pleural mesothelioma (MPM) is a relative rare but highly aggressive neoplasm which is associated with asbestos exposure in most patients. The majority of patients are diagnosed in advanced stages so patients neither benefit from chemotherapy (e.g. pemetrexed-platinum combination) nor from surgery. It has been reported that cellular-mesenchymal to epithelial transition factor (MET) and epidermal growth factor receptor (EGFR) were critical for MPM cell proliferation. Moreover, targeting MET and EGFR drugs have gained promising results on anti-tumor therapy. Here, a striking difference in overall survival was observed between the MET and EGFR co-expression group (median survival time = 13.5 months) and non-co-expression group (median survival time = 20.5 months). In addition, treatment with combination of crizotinib and afatinib showed stronger inhibition on cell proliferation of MPM than the treatment by either one in vitro and in vivo. In conclusion, our data illustrated that crizotinib combined with afatinib may be a potentially effective strategy for treating MPM patients with over-expression of MET and EGFR.}, } @article {pmid28335760, year = {2017}, author = {Ak, G and Tada, Y and Shimada, H and Metintas, S and Ito, M and Hiroshima, K and Tagawa, M and Metintas, M}, title = {Midkine is a potential novel marker for malignant mesothelioma with different prognostic and diagnostic values from mesothelin.}, journal = {BMC cancer}, volume = {17}, number = {1}, pages = {212}, pmid = {28335760}, issn = {1471-2407}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*blood ; Cohort Studies ; Cytokines/*blood ; Female ; GPI-Linked Proteins/*blood ; Humans ; Lung Neoplasms/*blood/diagnosis/*epidemiology ; Male ; Mesothelin ; Mesothelioma/*blood/diagnosis/*epidemiology ; Mesothelioma, Malignant ; Middle Aged ; Midkine ; Prognosis ; ROC Curve ; Turkey/epidemiology ; }, abstract = {BACKGROUND: We evaluated possible diagnostic and prognostic values of serum midkine in malignant pleural mesothelioma in comparison with those of serum mesothelin, a well-established diagnostic biomarker.

METHODS: Serum mesothelin and midkine levels were determined with an enzyme-linked immunosorbent assay. We examined specimens from 95 Turkish cases with malignant pleural mesothelioma, 56 metastatic cancers to pleura, 27 other types of benign pleural diseases and 20 benign asbestos pleurisy. The cut-off values were 1.5 nmol/L for mesothelin and 421 pg/mL for midkine.

RESULTS: Sensitivity and specificity of mesothelin were 51.6 and 71.4%, 51.6 and 85.2%, and 51.6 and 85% for differentiating mesothelioma from metastatic cancers to pleura, other benign pleural diseases and benign asbestos pleurisy, respectively. Sensitivity and specificity of midkine were 61.1 and 41.1%, 61.1 and 48.1%, and 61.1 and 75% to distinguish mesothelioma from metastatic cancers to pleura, other benign pleural diseases and benign asbestos pleurisy, respectively. Combination of both biomarkers did not improve the differential diagnostic efficacy. Mesothelin levels were elevated in the epitheloid type and in the advanced cases, but were not related to the prognosis. In contrast, elevated baseline levels of midkine were independently associated with a poor prognosis of mesothelioma patients after adjusting for the stage, the histological subtypes and treatment schedules (HR = 1.84; 95% CI: 1.09-3.09) (p = 0.022).

CONCLUSIONS: Serum mesothelin showed moderate sensitivity and high specificity to differentiate malignant pleural mesothelioma from metastatic malignancy to pleura and from benign pleural diseases. In contrast, midkine was a useful marker for predicting prognosis of mesothelioma patients.}, } @article {pmid28322788, year = {2017}, author = {Raiko, I and Rihs, HP and Gleichenhagen, J and Sander, I and Kollmeier, J and Lehnert, M and Brüning, T and Johnen, G}, title = {A recombinant polypeptide of the megakaryocyte potentiating factor is a potential biomarker in plasma for the detection of mesothelioma.}, journal = {Biochemical and biophysical research communications}, volume = {486}, number = {2}, pages = {526-532}, doi = {10.1016/j.bbrc.2017.03.077}, pmid = {28322788}, issn = {1090-2104}, mesh = {Adult ; Aged ; Aged, 80 and over ; Animals ; Antibodies/chemistry/isolation & purification ; Area Under Curve ; Biomarkers, Tumor/*blood/immunology ; Case-Control Studies ; Enzyme-Linked Immunosorbent Assay/*methods ; Escherichia coli/genetics/metabolism ; Female ; GPI-Linked Proteins/*blood/immunology ; HeLa Cells ; Humans ; Lung Neoplasms/blood/*diagnosis/immunology/pathology ; Male ; Mesothelin ; Mesothelioma/blood/*diagnosis/immunology/pathology ; Mesothelioma, Malignant ; Middle Aged ; Peptides/administration & dosage/*immunology/metabolism ; ROC Curve ; Rabbits ; Recombinant Proteins/administration & dosage/biosynthesis/immunology ; }, abstract = {Malignant mesothelioma (MM) is a fatal disease mostly associated with asbestos exposure and difficult to detect by non-invasive methods. This study aimed to use recombinant fragments of the megakaryocyte potentiating factor (MPF) for the development of cost-effective MPF ELISAs. Three polypeptides spanning the MPF region (MPF1-148, MPF 34-288, MPF/MSLN254-400) were produced in E.coli as maltose-binding protein hybrids. After isolation, Factor Xa digest, and purification, the polypeptides were used for the generation of rabbit antibodies and development of ELISAs. Forty-one MM patients with known histological subtype before tumor-specific treatment and 70 asbestos-exposed individuals free of any cancer were matched according to age, gender, and smoking. Plasma of all subjects was tested with the three newly developed polyclonal antibody-based ELISAs and a commercial mesothelin assay (MESOMARK™). The latter differentiated patients (median concentration 1.95 nM) from controls (median 1.07 nM, p < 0.0001) and showed an area under curve (AUC) of 0.77 in receiver operating characteristics (ROC) analysis. Of the MPF variants, exclusively the ELISA based on antibodies against the MPF34-288 fragment displayed significantly (p = 0.0002) higher values in patients than in controls (median 1.61 nM versus 0.88 nM; AUC = 0.72). The combination of the MPF34-288 and mesothelin displayed an improved ROC performance (AUC = 0.80). The MPF34-288 ELISA could be a cost-effective and minimal-invasive contribution to support a diagnosis of mesothelioma, especially in regions with a limited medical care.}, } @article {pmid28321148, year = {2017}, author = {Weber, DG and Gawrych, K and Casjens, S and Brik, A and Lehnert, M and Taeger, D and Pesch, B and Kollmeier, J and Bauer, TT and Johnen, G and Brüning, T}, title = {Circulating miR-132-3p as a Candidate Diagnostic Biomarker for Malignant Mesothelioma.}, journal = {Disease markers}, volume = {2017}, number = {}, pages = {9280170}, pmid = {28321148}, issn = {1875-8630}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/blood/*genetics ; Early Detection of Cancer ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/*diagnosis/genetics ; Male ; Mesothelioma/*diagnosis/genetics ; Mesothelioma, Malignant ; MicroRNAs/*blood ; Middle Aged ; Oligonucleotide Array Sequence Analysis/*methods ; Sensitivity and Specificity ; }, abstract = {The use of circulating microRNAs as biomarkers has opened new opportunities for diagnosis of cancer because microRNAs exhibit tumor-specific expression profiles. The aim of this study was the identification of circulating microRNAs in human plasma as potential biomarkers for the diagnosis of malignant mesothelioma. For discovery, TaqMan Low Density Array Human MicroRNA Cards were used to analyze 377 microRNAs in plasma samples from 21 mesothelioma patients and 21 asbestos-exposed controls. For verification, individual TaqMan microRNA assays were used for quantitative real-time PCR in plasma samples from 22 mesothelioma patients and 44 asbestos-exposed controls. The circulating miR-132-3p showed different expression levels between mesothelioma patients and asbestos-exposed controls. For discrimination, sensitivity of 86% and specificity of 61% were calculated. Circulating miR-132-3p in plasma was not affected by hemolysis and no impact of age or smoking status on miR-132-3p levels could be observed. For the combination of miR-132-3p with the previously described miR-126, sensitivity of 77% and specificity of 86% were calculated. The results of this study indicate that miR-132-3p might be a new promising diagnostic biomarker for malignant mesothelioma. It is indicated that the combination of miR-132-3p with other individual biomarkers improves the biomarker performance.}, } @article {pmid28279517, year = {2017}, author = {Diego Roza, C and Cruz Carmona, MJ and Fernández Álvarez, R and Ferrer Sancho, J and Marín Martínez, B and Martínez González, C and Rodríguez Portal, JA and Romero Valero, F and Villena Garrido, V}, title = {Recommendations for the Diagnosis and Management of Asbestos-Related Pleural and Pulmonary Disease.}, journal = {Archivos de bronconeumologia}, volume = {53}, number = {8}, pages = {437-442}, doi = {10.1016/j.arbres.2016.12.014}, pmid = {28279517}, issn = {1579-2129}, mesh = {Asbestos/classification/toxicity ; Asbestosis/*diagnosis/diagnostic imaging/prevention & control/*therapy ; Biomarkers, Tumor ; Carcinoma, Bronchogenic/diagnosis/etiology/therapy ; Humans ; Lung Neoplasms/diagnosis/etiology/therapy ; Mass Screening ; Mesothelioma/diagnosis/etiology/therapy ; Mineral Fibers/analysis/toxicity ; Occupational Exposure ; Occupational Health/legislation & jurisprudence ; Pleural Diseases/diagnosis/diagnostic imaging/therapy ; Pleural Neoplasms/diagnosis/etiology/therapy ; Positron Emission Tomography Computed Tomography ; Respiratory Function Tests ; Smoking/epidemiology ; Spain ; }, abstract = {Asbestos is the term used for a set of mineral silicates that tend to break up into fibers. Its use has been associated with numerous diseases affecting the lung and pleura in particular, all of which are characterized by their long period of latency. Asbestos, moreover, has been recognized by the WHO as a Group IA carcinogen since 1987 and its use was banned in Spain in 2002. The publication in 2013 of the 3rd edition of the specific asbestos health monitoring protocol, together with the development of new diagnostic techniques, prompted the SEPAR EROM group to sponsor publication of guidelines, which review the clinical, radiological and functional aspects of the different asbestos-related diseases. Recommendations have also been made for the diagnosis and follow-up of exposed patients. These recommendations were drawn up in accordance with the GRADE classification system.}, } @article {pmid28272659, year = {2018}, author = {Bianchi, C and Bianchi, T}, title = {Non-Hodgkin Lymphoma and Pleural Mesothelioma in a Person Exposed to Asbestos.}, journal = {Turk patoloji dergisi}, volume = {34}, number = {2}, pages = {190-193}, doi = {10.5146/tjpath.2015.01332}, pmid = {28272659}, issn = {1309-5730}, mesh = {Aged ; Asbestos/*adverse effects ; Female ; Humans ; Lung Neoplasms/etiology/*pathology ; Lymphoma, Non-Hodgkin/etiology/*pathology ; Mesothelioma/etiology/*pathology ; Mesothelioma, Malignant ; Neoplasms, Multiple Primary/*etiology/pathology ; Occupational Exposure/adverse effects ; Pleural Neoplasms/etiology/*pathology ; }, abstract = {Non-Hodgkin lymphoma and pleural mesothelioma may co-exist in the same patient. A large cell non-Hodgkin lymphoma of the inguinal lymph nodes was diagnosed in a 73-year-old woman. The patient was treated by chemotherapy. She did not receive radiotherapy. The patient had been exposed to asbestos having worked in a cotton mill and in a distillery. Four years after the diagnosis of lymphoma, she presented with a left pleural effusion. Large biopsies of the pleura showed a malignant mesothelioma, biphasic type, and pleural plaques. Epidemiological studies about the asbestos-lymphoma relationship gave conflicting results. The lymphoma-mesothelioma association is not exceptional, and suggests that asbestos plays a role in the etiology of both malignancies.}, } @article {pmid28253224, year = {2017}, author = {Mazurek, JM and Syamlal, G and Wood, JM and Hendricks, SA and Weston, A}, title = {Malignant Mesothelioma Mortality - United States, 1999-2015.}, journal = {MMWR. Morbidity and mortality weekly report}, volume = {66}, number = {8}, pages = {214-218}, pmid = {28253224}, issn = {1545-861X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/toxicity ; Cause of Death ; Female ; Humans ; Inhalation Exposure/adverse effects ; Lung Neoplasms/etiology/*mortality ; Male ; Mesothelioma/etiology/*mortality ; Mesothelioma, Malignant ; Middle Aged ; Mineral Fibers/adverse effects ; Occupational Diseases/etiology/mortality ; Occupational Exposure/adverse effects ; United States/epidemiology ; }, abstract = {Malignant mesothelioma is a neoplasm associated with occupational and environmental inhalation exposure to asbestos* fibers and other elongate mineral particles (EMPs) (1-3). Patients have a median survival of approximately 1 year from the time of diagnosis (1). The latency period from first causative exposure to malignant mesothelioma development typically ranges from 20 to 40 years but can be as long as 71 years (2,3). Hazardous occupational exposures to asbestos fibers and other EMPs have occurred in a variety of industrial operations, including mining and milling, manufacturing, shipbuilding and repair, and construction (3). Current exposures to commercial asbestos in the United States occur predominantly during maintenance operations and remediation of older buildings containing asbestos (3,4). To update information on malignant mesothelioma mortality (5), CDC analyzed annual multiple cause-of-death records[†] for 1999-2015, the most recent years for which complete data are available. During 1999-2015, a total of 45,221 deaths with malignant mesothelioma mentioned on the death certificate as the underlying or contributing cause of death were reported in the United States, increasing from 2,479 deaths in 1999 to 2,597 in 2015 (in the same time period the age-adjusted death rates[§] decreased from 13.96 per million in 1999 to 10.93 in 2015). Malignant mesothelioma deaths increased for persons aged ≥85 years, both sexes, persons of white, black, and Asian or Pacific Islander race, and all ethnic groups. Despite regulatory actions and the decline in use of asbestos the annual number of malignant mesothelioma deaths remains substantial. The continuing occurrence of malignant mesothelioma deaths underscores the need for maintaining measures to prevent exposure to asbestos fibers and other causative EMPs and for ongoing surveillance to monitor temporal trends.}, } @article {pmid28244608, year = {2017}, author = {Markowitz, SB and Moline, JM}, title = {Malignant mesothelioma due to asbestos exposure in dental tape.}, journal = {American journal of industrial medicine}, volume = {60}, number = {5}, pages = {437-442}, doi = {10.1002/ajim.22696}, pmid = {28244608}, issn = {1097-0274}, mesh = {Aged ; Asbestos/*adverse effects ; Dental Casting Technique/adverse effects ; Dentists ; Female ; Humans ; Lung Neoplasms/*chemically induced/diagnostic imaging ; Male ; Mesothelioma/*chemically induced/diagnostic imaging ; Mesothelioma, Malignant ; Middle Aged ; Occupational Diseases/*chemically induced ; Occupational Exposure/*adverse effects ; United States ; }, abstract = {Although most cases of malignant mesothelioma of the pleura are caused by one or more readily recognized sources of exposure to asbestos, cases of the disease with more occult exposure occur, especially since asbestos has been used in over 3,000 products. Dental lining tape contained asbestos from the 1930s until at least the 1970s and was used in the lost wax method of casting crowns, bridges, and other metal dental prosthetic devices. We report six cases of pathology-verified malignant mesothelioma, mostly among dentists, following exposure to airborne dust from asbestos dental tape, which resulted in asbestos tort litigation. According to evidence available at present, chrysotile asbestos was the type of asbestos used in dental tape in the past in the United States, and the described cases followed relatively brief and intermittent exposure to this type of asbestos. These cases underscore the need for comprehensive exposure histories to determine exposure scenarios. Am. J. Ind. Med. 60:437-442, 2017. © 2017 Wiley Periodicals, Inc.}, } @article {pmid28244606, year = {2017}, author = {Musk, B and Gordon, L and Alfonso, H and Reid, A and Olsen, N and Mina, R and Franklin, P and Peters, S and Brims, F and Hui, J and de Klerk, N}, title = {Risk factors for malignant mesothelioma in people with no known exposure to asbestos.}, journal = {American journal of industrial medicine}, volume = {60}, number = {5}, pages = {432-436}, doi = {10.1002/ajim.22695}, pmid = {28244606}, issn = {1097-0274}, mesh = {Asbestos/*adverse effects ; Case-Control Studies ; Environmental Exposure/*adverse effects ; Humans ; Interviews as Topic ; Lung Neoplasms/epidemiology/*etiology ; Mesothelioma/epidemiology/*etiology ; Mesothelioma, Malignant ; Occupational Diseases/etiology ; Occupational Exposure/adverse effects ; Registries ; Risk Factors ; Smoking ; Western Australia/epidemiology ; }, abstract = {OBJECTIVES: Malignant mesothelioma (MM) is a rare and generally fatal cancer, usually caused by asbestos, although about 5-10% of cases report no asbestos exposure. This study aimed to identify sources whereby people in Western Australia (WA) may be unknowingly exposed to asbestos or to other exposures which may cause MM.

METHODS: Cases with no known asbestos exposure were selected from the WA Mesothelioma Register (WAMR). Matched controls were selected from hospital patients admitted for conditions unrelated to asbestos. Occupational histories were coded by an industrial hygienist. Data were analyzed using conditional logistic regression.

RESULTS: Thirty-eight MM participants and 134 controls were recruited. Risk of MM was increased (OR = 3.1, 95%CI 1.0-9.6) after no known, but likely, exposure to asbestos at work.

CONCLUSIONS: Because of its extensive use, few people in WA have never been exposed to asbestos. Unrecognized exposure may cause most MM cases initially regarded as "no exposure." Am. J. Ind. Med. 60:432-436, 2017. © 2017 Wiley Periodicals, Inc.}, } @article {pmid28241714, year = {2017}, author = {Ying, SB and Tong, Y and Jiang, ZQ}, title = {[Molecular mechanisms of HMGB1 extracellular secretion in asbestos-induced malignant mesothelioma].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {35}, number = {1}, pages = {76-78}, doi = {10.3760/cma.j.issn.1001-9391.2017.01.022}, pmid = {28241714}, issn = {1001-9391}, } @article {pmid28241368, year = {2017}, author = {Lipp, MJ and Jusufi, MS and Backer, C and Feyerabend, B and Weilert, H and Oldhafer, KJ}, title = {[Benign multicystic peritoneal mesothelioma (BMPM) - a surprising differential diagnosis in case of an expected intraabdominal abscess formation].}, journal = {Zeitschrift fur Gastroenterologie}, volume = {55}, number = {3}, pages = {267-273}, doi = {10.1055/s-0043-100104}, pmid = {28241368}, issn = {1439-7803}, mesh = {Abdominal Abscess/*diagnosis/*etiology/therapy ; Adult ; Diagnosis, Differential ; Female ; Humans ; Mesothelioma, Cystic/*complications/*diagnostic imaging/therapy ; Peritoneal Neoplasms/*complications/*diagnostic imaging/therapy ; }, abstract = {The benign multicystic peritoneal mesothelioma is a rare disease. Most frequently, young women in reproductive age are affected by this disease. Nevertheless, there are known cases of multicystic peritoneal mesothelioma in male patients. The pathogenesis remains uncertain. Whereas asbestos fibers can cause the development of malignant mesothelioma, the exposure to asbestos particles cannot induce this type of mesothelioma. An inflammatory genesis is discussed as well as the idea of a neoplastic development. Since a high rate of recurrence after surgery is observed, an aggressive surgical treatment is recommended. The complete resection of affected tissue is recently considered to be the therapy of choice. The combination of complete surgical tumor reduction with an intraperitoneal hyperthermic chemotherapy (HIPEC) seems to be promising. Although malignant transformation is detected very rarely a close follow up in centers with high surgical and oncological expertise is recommended.}, } @article {pmid28236494, year = {2017}, author = {Ferrer, J and Sampol, J and Cruz, MJ}, title = {Malignant pleural mesothelioma in a young adult with no known exposure to asbestos. Can asbestos exposure be truly ruled out?.}, journal = {Archivos de bronconeumologia}, volume = {53}, number = {8}, pages = {469}, doi = {10.1016/j.arbres.2017.01.007}, pmid = {28236494}, issn = {1579-2129}, mesh = {Adult ; *Asbestos ; Environmental Exposure ; Humans ; Lung Neoplasms ; *Mesothelioma ; Occupational Exposure ; Pleural Neoplasms ; Young Adult ; }, } @article {pmid28210162, year = {2016}, author = {Patel, SC and Dowell, JE}, title = {Modern management of malignant pleural mesothelioma.}, journal = {Lung Cancer (Auckland, N.Z.)}, volume = {7}, number = {}, pages = {63-72}, pmid = {28210162}, issn = {1179-2728}, abstract = {Malignant pleural mesothelioma (MPM) is a deadly disease that produces a significant worldwide health care burden. The majority of cases are associated with prior asbestos exposure, but recent studies have identified a possible genetic predisposition in a minority of patients. Historically, obtaining a pathologic diagnosis of MPM was challenging, but with current pathological techniques, a secure diagnosis is possible in the majority of patients. Curative therapy for MPM remains elusive, and the primary treatment option for fit patients is platinum-based chemotherapy. Encouraging recent reports suggest that there may be a benefit to the addition of bevacizumab to standard chemotherapy as well as with the use of immune checkpoint inhibitors in MPM. Selected patients may be considered for aggressive surgical approaches, but there is considerable controversy regarding the true benefit of surgery and multimodality therapy in this disease.}, } @article {pmid28204714, year = {2017}, author = {Swiatkowska, B and Szeszenia-Dabrowska, N}, title = {Long-term epidemiological observation of asbestos-related diseases in Poland, 1970-2015.}, journal = {Occupational medicine (Oxford, England)}, volume = {67}, number = {3}, pages = {182-187}, doi = {10.1093/occmed/kqx011}, pmid = {28204714}, issn = {1471-8405}, mesh = {Asbestos/*toxicity ; Asbestosis/epidemiology/etiology ; Female ; Humans ; Lung Neoplasms/chemically induced/epidemiology ; Male ; Mesothelioma/chemically induced/epidemiology ; Mesothelioma, Malignant ; Occupational Diseases/chemically induced/*epidemiology ; Occupational Exposure ; Pleural Diseases/chemically induced/epidemiology ; Poland/epidemiology ; Population Surveillance ; }, abstract = {BACKGROUND: Occupational exposure to asbestos constitutes a major public health concern. Despite this in many countries, data and registration systems for occupational asbestos-related diseases are non-existent or poorly developed.

AIMS: To analyse the incidence of occupational asbestos-related diseases in Poland between the years 1970 and 2015, with particular emphasis on the periods after introduction of a ban on asbestos and following introduction of a surveillance programme.

METHODS: Analysis based on all medically recognized cases, certified as occupational diseases and reported obligatorily from all over the country to the Central Register of Occupational Diseases.

RESULTS: During the period 1970-2015, 4983 cases were reported as asbestos-related diseases. The most prevalent were asbestosis, lung cancer, diseases of pleura or pericardium and mesothelioma. A considerable increase in the number of such cases from the beginning of their registration until 2004 occurred after introduction of the Amiantus programme, a nationwide programme of periodic medical examinations for former asbestos workers.

CONCLUSIONS: Introduction of a medical surveillance programme improved case recognition and allowed a more reliable estimate of the number of reported asbestos-related diseases.}, } @article {pmid28197633, year = {2017}, author = {Mawas, AS and Amatya, VJ and Suzuki, R and Kushitani, K and Mohi El-Din, MM and Takeshima, Y}, title = {PIM1 knockdown inhibits cell proliferation and invasion of mesothelioma cells.}, journal = {International journal of oncology}, volume = {50}, number = {3}, pages = {1029-1034}, doi = {10.3892/ijo.2017.3863}, pmid = {28197633}, issn = {1791-2423}, mesh = {Apoptosis/genetics ; Cell Line, Tumor ; Cell Movement/*genetics ; Cell Proliferation/*genetics ; Cell Survival/genetics ; G1 Phase Cell Cycle Checkpoints/*genetics ; Humans ; Lung Neoplasms/*genetics/*pathology ; Mesothelioma/*genetics/*pathology ; Mesothelioma, Malignant ; Neoplasm Invasiveness/genetics ; Proto-Oncogene Proteins c-pim-1/*genetics ; RNA Interference ; RNA, Small Interfering/genetics ; }, abstract = {Malignant mesothelioma is a major asbestos-related cancer with prolonged time lapse from the first exposure of asbestos to the development of mesothelioma. Most of mesothelioma patients show very poor prognosis, thus, an urgent improvement of its treatment is required by development of novel therapeutic strategies. RNA interference (RNAi) is a powerful tool in post-genomic research and cancer therapy through inhibition of gene expression. In the present study, we analyzed the function of PIM1 on mesothelioma cell lines with its knockdown by siRNA transfection. Here, we report that the downregulation of PIM1 led to suppression of cell proliferation by cell cycle arrest at G1 phase and suppression of cell invasion and migration. Considering the mesothelioma as rapidly growing invasive cancer, downregulation of PIM1 may have a potential role for therapeutic management of malignant mesothelioma.}, } @article {pmid28197626, year = {2017}, author = {Cregan, S and Breslin, M and Roche, G and Wennstedt, S and MacDonagh, L and Albadri, C and Gao, Y and O'Byrne, KJ and Cuffe, S and Finn, SP and Gray, SG}, title = {Kdm6a and Kdm6b: Altered expression in malignant pleural mesothelioma.}, journal = {International journal of oncology}, volume = {50}, number = {3}, pages = {1044-1052}, doi = {10.3892/ijo.2017.3870}, pmid = {28197626}, issn = {1791-2423}, mesh = {Apoptosis/drug effects ; Benzazepines/*therapeutic use ; Cell Line, Tumor ; Cell Proliferation/drug effects/genetics ; Cell Survival/drug effects ; Cisplatin/therapeutic use ; Cytokines/*biosynthesis ; Gene Expression Regulation, Neoplastic ; Histone Demethylases/*biosynthesis/genetics ; Humans ; Jumonji Domain-Containing Histone Demethylases/*biosynthesis/genetics ; Lung Neoplasms/*drug therapy/genetics/pathology ; Mesothelioma/*drug therapy/genetics/pathology ; Mesothelioma, Malignant ; Nuclear Proteins/*biosynthesis/genetics ; Pemetrexed/therapeutic use ; Pyrimidines/*therapeutic use ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare aggressive cancer of the pleura primarily associated with prior exposure to asbestos. The current standard of care for patients suffering from MPM is a combination of cisplatin and pemetrexed (or alternatively cisplatin and raltitrexed). Most patients, however, die within 24 months of diagnosis. New therapies are therefore urgently required for this disease. Inflammation is thought to be a key element in the pathogenesis of MPM, and recently Kdm6 family members (Kdm6a and Kdm6b) have been identified as playing important roles in inflammatory processes. As such these genes could potentially represent novel candidate targets for intervention in MPM. Using RT-PCR we examined the expression of Kdm6aA and Kdm6b in a panel of MPM cell lines and in a cohort of snap-frozen patient samples isolated at surgery comprising benign, epithelial, biphasic and sarcomatoid histologies. Both Kdm6a and Kdm6b were found to be significantly overexpressed in MPM at the mRNA level. However, tests examining if targeting therapeutically Kdm6a/b using a specific small molecule inhibitor (GSK-J4) was potentially useful for treating MPM, revealed that anti-proliferative activity was higher at lower drug concentrations in cell lines derived from normal mesothelial cells compared to those derived from malignant cells. Treatments with GSK-J4 were found to be associated with the induction of apoptosis and increased expression of pro-inflammatory cytokines. As such our results demonstrate that whilst members of the Kdm6 family are overexpressed in MPM they may not be suitable candidates for therapy and may elicit a cytokine storm.}, } @article {pmid28191281, year = {2016}, author = {Nabavi, N and Bennewith, KL and Churg, A and Wang, Y and Collins, CC and Mutti, L}, title = {Switching off malignant mesothelioma: exploiting the hypoxic microenvironment.}, journal = {Genes & cancer}, volume = {7}, number = {11-12}, pages = {340-354}, pmid = {28191281}, issn = {1947-6019}, abstract = {Malignant mesotheliomas are aggressive, asbestos-related cancers with poor patient prognosis, typically arising in the mesothelial surfaces of tissues in pleural and peritoneal cavity. The relative unspecific symptoms of mesotheliomas, misdiagnoses, and lack of precise targeted therapies call for a more critical assessment of this disease. In the present review, we categorize commonly identified genomic aberrations of mesotheliomas into their canonical pathways and discuss targeting these pathways in the context of tumor hypoxia, a hallmark of cancer known to render solid tumors more resistant to radiation and most chemo-therapy. We then explore the concept that the intrinsic hypoxic microenvironment of mesotheliomas can be Achilles' heel for targeted, multimodal therapeutic intervention.}, } @article {pmid28188891, year = {2017}, author = {Bonassi, S and Cellai, F and Munnia, A and Ugolini, D and Cristaudo, A and Neri, M and Milić, M and Bonotti, A and Giese, RW and Peluso, ME}, title = {3-(2-deoxy-β-d-erythro-pentafuranosyl)pyrimido[1,2-α]purin-10(3H)-one deoxyguanosine adducts of workers exposed to asbestos fibers.}, journal = {Toxicology letters}, volume = {270}, number = {}, pages = {1-7}, pmid = {28188891}, issn = {1879-3169}, support = {P42 ES017198/ES/NIEHS NIH HHS/United States ; }, mesh = {Aged ; Asbestos/blood/*toxicity ; Biomarkers/blood ; Cross-Sectional Studies ; DNA Adducts/*blood ; Deoxyguanosine/blood/*toxicity ; Educational Status ; Humans ; Italy ; Lipid Peroxidation/drug effects ; Male ; Middle Aged ; Occupational Exposure/*adverse effects ; Oxidative Stress/drug effects ; Purine Nucleosides/blood/*toxicity ; Reactive Oxygen Species/metabolism ; Smoking ; }, abstract = {Asbestos is the commercial name for a group of silicate minerals naturally occurring in the environment and widely used in the industry. Asbestos exposure has been associated with pulmonary fibrosis, mesothelioma, and malignancies, which may appear after a period of latency of 20-40 years. Mechanisms involved in the carcinogenic effects of asbestos are still not fully elucidated, although the oxidative stress theory suggests that phagocytic cells produce large amounts of reactive oxygen species, due to their inability to digest asbestos fiber. We have conducted a mechanistic study to evaluate the association between 3-(2-deoxy-β-d-erythro-pentafuranosyl)pyrimido[1,2-α]purin-10(3H)-one deoxyguanosine (M1dG) adducts, a biomarker of oxidative stress and lipid peroxidation, and asbestos exposure in the peripheral blood of 327 subjects living in Tuscany and Liguria, Italy, stratified by occupational exposure to asbestos. Adduct frequency was significantly greater into exposed subjects with respect to the controls. M1dG per 10[8] normal nucleotides were 4.0±0.5 (SE) in 156 asbestos workers, employed in mechanic, naval, petrochemical, building industries, and in pottery and ceramic plants, versus a value of 2.3±0.1 (SE) in 171 controls (p<0.001). After stratification for occupational history, the effects persisted in 54 current asbestos workers, mainly employed in building renovation industry (2.9±0.3 (SE)), and in 102 former asbestos workers (4.5±0.7 (SE)), with p-values of 0.033, and <0.001, respectively. A significant effect of smoking on heavy smokers was found (p=0.005). Our study gives additional support to the oxidative stress theory, where M1dG may reflect an additional potential mechanism of asbestos-induced toxicity.}, } @article {pmid28186988, year = {2017}, author = {Pellegrini, L and Xue, J and Larson, D and Pastorino, S and Jube, S and Forest, KH and Saad-Jube, ZS and Napolitano, A and Pagano, I and Negi, VS and Bianchi, ME and Morris, P and Pass, HI and Gaudino, G and Carbone, M and Yang, H}, title = {HMGB1 targeting by ethyl pyruvate suppresses malignant phenotype of human mesothelioma.}, journal = {Oncotarget}, volume = {8}, number = {14}, pages = {22649-22661}, pmid = {28186988}, issn = {1949-2553}, support = {P30 CA071789/CA/NCI NIH HHS/United States ; R01 CA160715/CA/NCI NIH HHS/United States ; R01 CA198138/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Apoptosis ; Biomarkers, Tumor/*metabolism ; Cell Movement ; Cell Proliferation ; Female ; Gene Expression Regulation, Neoplastic/*drug effects ; HMGB1 Protein/*antagonists & inhibitors/metabolism ; Humans ; Mesothelioma/metabolism/pathology/*prevention & control ; Mice ; Mice, Inbred BALB C ; Mice, Inbred NOD ; Mice, SCID ; Neoplasm Staging ; Prognosis ; Pyruvates/*pharmacology ; Signal Transduction ; Tumor Cells, Cultured ; Xenograft Model Antitumor Assays ; }, abstract = {Human malignant mesothelioma (MM) is an aggressive cancer linked to asbestos and erionite exposure. We previously reported that High-Mobility Group Box-1 protein (HMGB1), a prototypic damage-associated molecular pattern, drives MM development and sustains MM progression. Moreover, we demonstrated that targeting HMGB1 inhibited MM cell growth and motility in vitro, reduced tumor growth in vivo, and prolonged survival of MM-bearing mice. Ethyl pyruvate (EP), the ethyl ester of pyruvic acid, has been shown to be an effective HMGB1 inhibitor in inflammation-related diseases and several cancers. Here, we studied the effect of EP on the malignant phenotype of MM cells in tissue culture and on tumor growth in vivo using an orthotopic MM xenograft model. We found that EP impairs HMGB1 secretion by MM cells leading to reduced RAGE expression and NF-κB activation. As a consequence, EP impaired cell motility, cell proliferation, and anchorage-independent growth of MM cells. Moreover, EP reduced HMGB1 serum levels in mice and inhibited the growth of MM xenografts.Our results indicate that EP effectively hampers the malignant phenotype of MM, offering a novel potential therapeutic approach to patients afflicted with this dismal disease.}, } @article {pmid28168071, year = {2017}, author = {Ramirez Sevilla, C and Admella Salvador, C and Feliu Canaleta, J and Llopis Manzanera, J and Barranco Sanz, MA and Romero Martin, JA and Bernal Salguero, S}, title = {Two Case Reports of Benign Testicular Mesothelioma and Review of the Literature.}, journal = {Case reports in oncological medicine}, volume = {2017}, number = {}, pages = {5419635}, pmid = {28168071}, issn = {2090-6706}, abstract = {Mesothelioma is usually diagnosed in people over the age of 50 with large history of asbestos-related exposure. It is frequently located in pleural cavity, peritoneum, and pericardium. At the testicles the mesothelioma had been reported first in 1957 like a malignant non-germ-cells tumor. The objective is to present two case reports of benign testicular mesothelioma and review of the literature.}, } @article {pmid28166467, year = {2018}, author = {Rusiecki, J and Stewart, P and Lee, D and Alexander, M and Krstev, S and Silverman, D and Blair, A}, title = {Mortality among Coast Guard Shipyard workers: A retrospective cohort study of specific exposures.}, journal = {Archives of environmental & occupational health}, volume = {73}, number = {1}, pages = {4-18}, doi = {10.1080/19338244.2017.1289891}, pmid = {28166467}, issn = {2154-4700}, mesh = {Adult ; Baltimore/epidemiology ; Cohort Studies ; Construction Industry/*statistics & numerical data ; Environmental Pollutants/*toxicity ; Female ; Humans ; Lung Neoplasms/chemically induced/epidemiology/*mortality ; Male ; Mesothelioma/chemically induced/epidemiology/*mortality ; Mesothelioma, Malignant ; Middle Aged ; Occupational Diseases/chemically induced/epidemiology/*mortality ; *Occupational Exposure ; Respiratory Tract Neoplasms/chemically induced/epidemiology/*mortality ; Retrospective Studies ; *Ships ; Young Adult ; }, abstract = {In a previous analysis of a cohort of shipyard workers, we found excess mortality from all causes, lung cancer, and mesothelioma for longer work durations and in specific occupations. Here, we expand the previous analyses by evaluating mortality associated with 5 chemical exposures: asbestos, solvents, lead, oils/greases, and wood dust. Data were gathered retrospectively for 4,702 workers employed at the Coast Guard Shipyard, Baltimore, MD (1950-1964). The cohort was traced through 2001 for vital status. Associations between mortality and these 5 exposures were calculated via standardized mortality ratios (SMRs). We found all 5 substances to be independently associated with mortality from mesothelioma, cancer of the respiratory system, and lung cancer. Findings from efforts to evaluate solvents, lead, oils/greases, and wood dust in isolation of asbestos suggested that the excesses from these other exposures may be due to residual confounding from asbestos exposure.}, } @article {pmid28162043, year = {2017}, author = {Smargiassi, A and Pasciuto, G and Pedicelli, I and Lo Greco, E and Calvello, M and Inchingolo, R and Schifino, G and Capoluongo, P and Patriciello, P and Manno, M and Cirillo, A and Corbo, GM and Soldati, G and Iavicoli, I}, title = {Chest ultrasonography in health surveillance of asbestos-related lung diseases.}, journal = {Toxicology and industrial health}, volume = {33}, number = {6}, pages = {537-546}, doi = {10.1177/0748233716686916}, pmid = {28162043}, issn = {1477-0393}, mesh = {Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Asbestosis/*diagnostic imaging ; Body Mass Index ; Cohort Studies ; Humans ; Lung/*diagnostic imaging/drug effects ; Male ; Middle Aged ; Occupational Exposure/*adverse effects ; Sensitivity and Specificity ; Tomography, X-Ray Computed ; Ultrasonography ; }, abstract = {OBJECTIVES: Exposure to asbestos fibers can lead to different lung diseases, such as pleural thickening and effusion, asbestosis, mesothelioma, and lung cancer. These diseases are expected to peak in the next few years. The aim of the study was to validate ultrasonography (US) as a diagnostic tool in the management of lung diseases in subjects with a history of occupational exposure to asbestos.

METHODS: Fifty-nine retired male workers previously exposed to asbestos were enrolled in the study. Chest US was performed in all the subjects. The US operator was blinded to earlier performed computed tomography (CT) scan reports and images. The sonographic pathological findings were pleural thickening (with or without calcifications), peripheral lung consolidation, and focal sonographic interstitial syndrome and diffuse pneumogenic sonographic interstitial syndrome (pulmonary asbestosis). Significant US findings were recorded, stored, and subsequently compared with CT scans.

RESULTS: With some patients falling into more than one category, on CT scan, pleural thickening was reported in 33 cases (56%, 26 with calcifications), focal interstitial peripheral alterations in 23 (39%), asbestosis in 6 (10%), and peripheral lung consolidation in 13 cases (22%). Comparing each pathological condition to CT scan reports, US findings had high levels of sensitivity, specificity, positive, and negative predictive values. US did not prove effective for the detection of central lung nodules or diaphragmatic pleural thickenings. Chest US was considered to be the best technique to detect minimal pleural effusions (six subjects, 10%).

CONCLUSIONS: Chest US might be considered an additional tool to follow up subjects occupationally exposed to asbestos who have already undergone CT scan examination and whose pathology is detectable by US as well.}, } @article {pmid28153512, year = {2017}, author = {Petrella, F and Coccè, V and Masia, C and Milani, M and Salè, EO and Alessandri, G and Parati, E and Sisto, F and Pentimalli, F and Brini, AT and Pessina, A and Spaggiari, L}, title = {Paclitaxel-releasing mesenchymal stromal cells inhibit in vitro proliferation of human mesothelioma cells.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {87}, number = {}, pages = {755-758}, doi = {10.1016/j.biopha.2017.01.118}, pmid = {28153512}, issn = {1950-6007}, mesh = {Antineoplastic Agents/*pharmacology ; Cell Line, Tumor ; Cell Proliferation/*drug effects ; Drug Delivery Systems/methods ; Drug Liberation ; Humans ; Lung Neoplasms/*drug therapy ; Mesenchymal Stem Cells/*drug effects ; Mesothelioma/*drug therapy ; Mesothelioma, Malignant ; Paclitaxel/*pharmacology ; Pemetrexed/pharmacology ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is a rare fatal asbestos-related malignancy originating in the mesothelial cells of the pleura. A platinum-based doublet containing a third-generation antifolate is the front-line standard of care whilst there are no approved second-line treatments for MPM which remains a disease setting to test the efficacy of new therapeutic agents.

METHODS: Bone marrow mesenchymal stromal cells (BM-MSCs) were loaded with pemetrexed (PMX) and paclitaxel (PTX) according to a standardized procedure. Drug release by both PMX- and PTX-primed BM-MSCs (BM-MSCs/PMX and BM-MSCs/PTX) was tested on the in vitro proliferation of a panel of tumor cell lines including NCI-H28 mesothelioma.

RESULTS: The in vitro anticancer activity of pure PTX was significantly higher than that of PMX against all the cell lines tested (14.7 times higher than that of PMX against NCI-H28). Whereas BM-MSCs did not take up and release PMX in amounts effective on mesothelioma, PTX-loaded BM-MSCs dramatically inhibited mesothelioma proliferation.

CONCLUSIONS: PTX-primed mesenchymal stromal cells successfully inhibit the in vitro proliferation of human mesothelioma cells. Further studies and in vivo testing are required to confirm our preliminary in vitro results as a potential new mesothelioma therapy based on cell drug delivery.}, } @article {pmid28151477, year = {2017}, author = {Zonca, S and Pinton, G and Wang, Z and Soluri, MF and Tavian, D and Griffin, M and Sblattero, D and Moro, L}, title = {Tissue transglutaminase (TG2) enables survival of human malignant pleural mesothelioma cells in hypoxia.}, journal = {Cell death & disease}, volume = {8}, number = {2}, pages = {e2592}, pmid = {28151477}, issn = {2041-4889}, mesh = {Adaptation, Biological/genetics ; Biomarkers, Tumor/genetics ; Cell Line, Tumor ; Cell Proliferation/genetics ; Cell Survival/*genetics ; GTP-Binding Proteins/*genetics ; Gene Expression Regulation, Neoplastic ; Gene Silencing/physiology ; Humans ; Hypoxia/*genetics/pathology ; Lung Neoplasms/*genetics/pathology ; Mesothelioma/*genetics/pathology ; Mesothelioma, Malignant ; Pleural Neoplasms/*genetics/pathology ; Protein Glutamine gamma Glutamyltransferase 2 ; Transglutaminases/*genetics ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive tumor linked to environmental/occupational exposure to asbestos, characterized by the presence of significant areas of hypoxia. In this study, we firstly explored the expression and the role of transglutaminase 2 (TG2) in MPM cell adaptation to hypoxia. We demonstrated that cells derived from biphasic MPM express the full-length TG2 variant at higher levels than cells derived from epithelioid MPM and normal mesothelium. We observed a significant induction of TG2 expression and activity when cells from biphasic MPM were grown as a monolayer in chronic hypoxia or packed in spheroids, where the presence of a hypoxic core was demonstrated. We described that the hypoxic induction of TG2 was HIF-2 dependent. Importantly, TGM2-v1 silencing caused a marked and significant reduction of MPM cell viability in hypoxic conditions when compared with normoxia. Notably, a TG2-selective irreversible inhibitor that reacts with the intracellular active form of TG2, but not a non-cell-permeable inhibitor, significantly compromised cell viability in MPM spheroids. Understanding the expression and function of TG2 in the adaptation to the hypoxic environment may provide useful information for novel promising therapeutic options for MPM treatment.}, } @article {pmid28139858, year = {2017}, author = {Linton, A and Soeberg, M and Broome, R and Kao, S and van Zandwijk, N}, title = {Geographic and socioeconomic factors in patients with malignant pleural mesothelioma in New South Wales and their impact upon clinical outcomes.}, journal = {Respirology (Carlton, Vic.)}, volume = {22}, number = {5}, pages = {978-985}, doi = {10.1111/resp.12981}, pmid = {28139858}, issn = {1440-1843}, mesh = {Adult ; Aged ; Female ; Humans ; Incidence ; Lung Neoplasms/*diagnosis/*epidemiology/therapy ; Male ; Mesothelioma/*diagnosis/*epidemiology/therapy ; Mesothelioma, Malignant ; Middle Aged ; Multivariate Analysis ; New South Wales/epidemiology ; Pleural Neoplasms/*diagnosis/*epidemiology/therapy ; Pneumonectomy ; Prognosis ; Proportional Hazards Models ; Registries ; Socioeconomic Factors ; }, abstract = {BACKGROUND AND OBJECTIVE: Whilst the impact of clinicopathological factors on the prognosis of malignant pleural mesothelioma (MPM) is well understood, socioeconomic and geographic factors have received less attention. We analysed the relationship between geographic and socioeconomic factors upon survival and treatment provision in a large series of patients with MPM.

METHODS: We assessed MPM patients awarded compensation between 2002 and 2009 with additional MPM incidence data from the New South Wales (NSW) Cancer Registry. The impact of geographic remoteness, distance from oncological multidisciplinary team (MDT) and Index of Relative Socioeconomic Advantage and Disadvantage (IRSAD) upon survival, clinical features and treatment received was analysed.

RESULTS: We identified 910 patients (67% residing in major cities; 92% <50 km from MDT). Median overall survival was 10.0 months. On multivariate analysis, age >70 (hazard ratio (HR) = 1.39), male gender (HR =1.36), non-epithelioid histological subtype (HR = 2.18) and IRSAD status by decreasing quintile (HR = 1.06) were independent prognostic factors. There was no significant advantage for patients residing in major cities (10.6 months vs 8.8 months; P = 0.162) or within 50 km of MDT (10.3 months vs 7.8 months; P = 0.539). Patient's geographic location and distance to MDT did not impact chemotherapy, adjuvant radiotherapy or extrapleural pneumonectomy provision. Socioeconomically disadvantaged patients were significantly less likely to receive chemotherapy (37.4% vs 54.8%; P = 0.001).

CONCLUSION: This study provides evidence for differences in the treatment and survival according to socioeconomic status for compensated MPM patients in NSW. Further research is warranted to seek additional explanations for the differences noted by comparing the treatments and outcomes of compensated and non-compensated MPM patients in NSW.}, } @article {pmid28133921, year = {2017}, author = {Gualtieri, AF}, title = {Sharing different perspectives to understand asbestos-induced carcinogenesis: A comment to Jiang et al. (2016).}, journal = {Cancer science}, volume = {108}, number = {1}, pages = {156-157}, pmid = {28133921}, issn = {1349-7006}, mesh = {*Asbestos ; *Carcinogenesis ; Humans ; Mesothelioma/chemically induced ; }, abstract = {This letter reports some constructive observations on the recent findings by Jiang et al. Cancer Sci (2016) that have inspired a more general comment on how the research on asbestos should take advantage of the different existing multidisciplinary perspectives so to flow into a final comprehensive model of asbestos‐induced carcinogenesis.}, } @article {pmid28133000, year = {2017}, author = {Micolucci, L and Rippo, MR and Olivieri, F and Procopio, AD}, title = {Progress of research on microRNAs with diagnostic value in asbestos exposure: A call for method standardization.}, journal = {Bioscience trends}, volume = {11}, number = {1}, pages = {105-109}, doi = {10.5582/bst.2016.01249}, pmid = {28133000}, issn = {1881-7823}, mesh = {Asbestos/*adverse effects ; Biomarkers, Tumor/metabolism ; Environmental Exposure/*analysis ; Humans ; Lung Neoplasms/*diagnosis ; Mesothelioma/*diagnosis ; Mesothelioma, Malignant ; MicroRNAs/*genetics/metabolism ; Reference Standards ; }, abstract = {Malignant mesothelioma (MM) is an insidious, lethal asbestos-related cancer that is poorly responsive to current treatments. Specific and sensitive biomarkers providing early MM diagnosis in exposed subjects, who are at high-risk of developing it, are sorely needed. MicroRNAs (miRNAs) are endogenous, non-coding, small RNAs with a well-established diagnostic role in cancer and pollution exposure. In a recent systematic review and qualitative meta-analysis followed by a functional investigation, we examined all the available data on the miRNA biomarkers involved in asbestos exposure and MM pathways. This invited commentary aims to provide an insightful critique into the state of the art of the research into clinically relevant miRNA biomarkers, highlighting the strengths and weaknesses of current research efforts in this field. It also reviews the suggestions advanced to improve biomarker development productivity and the translation of research results into clinical practice, stressing that multicenter multidisciplinary studies adopting standardized methods and protocol sharing are the key to move from the workbench to the clinic.}, } @article {pmid28132991, year = {2016}, author = {Kaneko, M and Minamikawa, T and Taniguchi, H and Yamada, Y and Nakamura, J and Okihara, K and Nakauchi, H}, title = {[MALIGNANT MESOTHELIOMA OF THE TUNICA VAGINALIS TESTIS: A CASE REPORT].}, journal = {Nihon Hinyokika Gakkai zasshi. The japanese journal of urology}, volume = {107}, number = {1}, pages = {44-47}, doi = {10.5980/jpnjurol.107.44}, pmid = {28132991}, issn = {0021-5287}, mesh = {Aged, 80 and over ; Cytodiagnosis ; Humans ; Lung Neoplasms/complications/*diagnosis/pathology/*surgery ; Magnetic Resonance Imaging ; Male ; Mesothelioma/complications/*diagnosis/pathology/*surgery ; Mesothelioma, Malignant ; Orchiectomy/methods ; Testicular Hydrocele/etiology/pathology/surgery ; Testicular Neoplasms/complications/*diagnosis/pathology/*surgery ; Ultrasonography ; }, abstract = {We report here a case of malignant mesothelioma of the tunica vaginalis testis. A 93-year-old man with no history of asbestos exposure complained of increase of right scrotum size with pain. Ultrasonography and magnetic resonance imaging revealed a right hydrocele testis. A cytologic examination of the hydrocele fluid demonstrated mesothelial cells but show less atypicality and lack of obvious malignant features (class IIIa). We performed right hydrocelectomy for hydrocele testis. The pathological diagnosis was epithelial type of malignant mesothelioma of the tunica vaginalis testis, therefore we performed radical orchidectomy with wide excision of hemi-scrotal wall. There is no evidence of recurrence after 6 months of follow up. Malignant mesothelioma of the tunica vaginalis is rare, and accurate preoperative diagnosis is difficult. When a rapid increasing hemorrhagic hydrocele testis or nodular masses of the tunica vaginalis was observed, malignant mesothelioma should be considered. Malignant mesothelioma is highly fatal disease. Even two stage operation, radical orchidectomy should be performed.}, } @article {pmid28123552, year = {2017}, author = {Nakamura, K and Nakayama, K and Nagaoka, R and Nishisako, K and Ishikawa, M and Katagiri, H and Ishibashi, T and Sato, E and Amano, C and Kyo, S}, title = {The diagnostic utility of PAX8 immunostaining of malignant peritoneal mesothelioma presenting as serous ovarian carcinoma: A single-center report of two cases.}, journal = {Oncology letters}, volume = {13}, number = {1}, pages = {263-266}, pmid = {28123552}, issn = {1792-1074}, abstract = {Malignant peritoneal mesotheliomas (MPMs) are rare and progressive tumors, which may present similarly to primary peritoneal carcinoma or ovarian carcinoma (OC). The current study reports two cases of MPM that initially presented with the features of OC, for which paired box 8 (PAX8) immunostaining was found to be useful for diagnosis. The two patients were women, aged 58 and 56 years, respectively. The primary presenting symptoms and clinical findings included prolonged abdominal pain, abdominal swelling and cough. The two cases were initially diagnosed as OC and were treated with primary debulking surgery. The patient in case 1 had no history of asbestos exposure, while the patient in case 2 did. Final diagnoses were determined based on histological and immunohistochemical results, which included negative PAX8 immunostaining, and which were consistent with MPM. The present cases demonstrated that PAX8 negativity may be a useful diagnostic biomarker for differentiating MPM from OC.}, } @article {pmid28105159, year = {2016}, author = {Fasano, M and Della Corte, CM and Vicidomini, G and Scotti, V and Rambaldi, PF and Fiorelli, A and Accardo, M and De Vita, F and Santini, M and Ciardiello, F and Morgillo, F}, title = {Small bowel metastasis from pancreatic cancer in a long-term survival patient with synchronous advanced malignant pleural mesothelioma: A case report and literature review.}, journal = {Oncology letters}, volume = {12}, number = {6}, pages = {4505-4509}, pmid = {28105159}, issn = {1792-1074}, abstract = {Diffuse malignant pleural mesothelioma (MPM) is an aggressive tumor that originates from the surface of the pleura. Approximately 70% of cases are associated with chronic asbestos exposure. MPM is regarded as an incurable disease, with a median survival of ~2 years following intensive multimodality treatment. Pancreatic cancer is a malignancy also associated with a poor prognosis, with only 2% of patients surviving for 5 years. The majority of patients with pancreatic cancer are diagnosed with an advanced stage of disease and experience a poor response to therapy. The development of synchronous MPM and other types of cancer is rare. The present study describes a patient with synchronous, biphasic MPM and pancreatic adenocarcinoma, who was treated with a multimodal therapeutic approach with stereotactic body radiation therapy. Due to a suspected diagnosis of 'acute abdomen', an emergency small intestine resection was performed and a subsequent diagnosis of moderately-differentiated adenocarcinoma was confirmed. During a further immunohistochemical examination, pathologists determined that the small bowel metastasis descended from pancreatic cancer. The onset of bowel metastasis is an event rarely associated with MPM, and has not been previously described in the literature for cases of pancreatic cancer. Therefore, to the best of our knowledge, the present study describes the first case of intestinal metastasis from pancreatic cancer in a long-term survival patient with biphasic MPM.}, } @article {pmid28095707, year = {2018}, author = {Si, S and Peters, S and Reid, A}, title = {Variations in mesothelioma mortality rates among migrants to Australia and Australian-born.}, journal = {Ethnicity & health}, volume = {23}, number = {5}, pages = {480-487}, doi = {10.1080/13557858.2017.1280138}, pmid = {28095707}, issn = {1465-3419}, mesh = {Adolescent ; Adult ; Africa/ethnology ; Aged ; Asia/ethnology ; Australia/epidemiology ; Emigrants and Immigrants/*statistics & numerical data ; Europe/ethnology ; Female ; Humans ; Lung Neoplasms/mortality ; Male ; Mesothelioma/*mortality ; Mesothelioma, Malignant ; Middle Aged ; Young Adult ; }, abstract = {BACKGROUND: Australia's use and consumption of asbestos occurred at the same time as its immigration boom. Our objective was to investigate mesothelioma death rates among migrants and Australian-born between 1981 and 2012.

METHODS: Australian national mesothelioma deaths from 1981 to 2002 and 2006 to 2012 together with national censuses from 1981 to 2011 were extracted and combined. Directly standardised rates and negative binomial regression were applied examining differences in mesothelioma death rates with regard to country of birth.

RESULTS: Migrants from the UK and Ireland, Italy and Germany had significantly higher mesothelioma death rates than Australian-born; lower rates were observed among migrants from other countries.

CONCLUSIONS: Our findings suggest there may have been differences in occupational health and safety between foreign and Australian-born. Because of changes in the demographics of migrants to Australia since the 1970s and changes in occupational circumstances over time, further comparisons of occupational-related health outcomes between foreign and Australian-born could identify potential occupational inequalities that may still exist today.}, } @article {pmid28090191, year = {2016}, author = {Sohn, EJ and Won, G and Lee, J and Yoon, SW and Lee, I and Kim, HJ and Kim, SH}, title = {Blockage of epithelial to mesenchymal transition and upregulation of let 7b are critically involved in ursolic acid induced apoptosis in malignant mesothelioma cell.}, journal = {International journal of biological sciences}, volume = {12}, number = {11}, pages = {1279-1288}, pmid = {28090191}, issn = {1449-2288}, mesh = {Apoptosis/drug effects ; Blotting, Western ; Cell Cycle/drug effects ; Cell Line, Tumor ; Epithelial-Mesenchymal Transition/*drug effects ; Humans ; Lung Neoplasms/*metabolism/*pathology ; Mesothelioma/*metabolism/*pathology ; Mesothelioma, Malignant ; MicroRNAs/genetics/metabolism ; Real-Time Polymerase Chain Reaction ; Transfection ; Triterpenes/*pharmacology ; Ursolic Acid ; }, abstract = {Malignant pleural mesothelioma (MPN), which is caused by asbestos exposure, is one of aggressive lung tumors. In the present study, we elucidated the anti-tumor mechanism of ursolic acid in malignant mesotheliomas. Ursolic acid significantly exerted cytotoxicity in a time and dose dependent manner in H28, H2452 and MSTO-211H mesothelioma cells and inhibited cell proliferation by colony formation assay in a dose-dependent fashion. Also, ursolic acid treatment accumulated the sub-G1 population, attenuated the expression of procapase 9, cyclin D1, pAKT, p-glycogen synthase kinase 3-alpha/beta (pGSK3α/β), β-catenin and nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB) and also cleaved caspase 3 and poly (ADP-ribose) polymerase (PARP) in mesothelioma cells. Furthermore, ursolic acid treatment blocked epithelial and mesenchymal transition (EMT) molecules by activating E-cadherin as an epithelial marker and attenuating Vimentin, and Twist as mesenchymal molecules. Interestingly, miRNA array revealed that 23 miRNAs (>2 folds) including let-7b and miRNA3613-5p, miRNA134 and miRNA196b were significantly upregulated while 33 miRNAs were downregulated in ursolic acid treated H2452 cells. Furthermore, overexpression of let 7b using let-7b mimics enhanced the antitumor effect of ursolic acid to attenuate the expression of procaspases 3, pro-PARP, pAKT, β-catenin and Twist and increase sub-G1 accumulation in H2452 mesothelioma cells. Overall, our findings suggest that ursolic acid induces apoptosis via inhibition of EMT and activation of let7b in mesothelioma cells as a potent chemotherapeutic agent for treatment of malignant mesotheliomas.}, } @article {pmid28079278, year = {2017}, author = {Egilman, D and Monárrez, R}, title = {Corporate corruption of science-Another asbestos example.}, journal = {American journal of industrial medicine}, volume = {60}, number = {2}, pages = {152-162}, doi = {10.1002/ajim.22686}, pmid = {28079278}, issn = {1097-0274}, mesh = {Asbestos/*toxicity ; Australia/epidemiology ; Automobiles ; Carcinogens/*toxicity ; Humans ; *Industry ; Mesothelioma/epidemiology/*etiology ; Occupational Diseases/epidemiology/*etiology ; Occupational Exposure/adverse effects ; Registries ; Research Design ; *Research Support as Topic ; }, abstract = {BACKGROUND: Kelsh et al. [2007]: Occup Med (Lond) 57:581-589 published a paper reanalyzing one of the few data sources publicly available on mesothelioma amongst brake workers, the Australian Mesothelioma Surveillance Registry (AMSR). This reanalysis was commissioned by lawyers representing the automobile manufacturing companies and did not align with an independent analysis published by Leigh and Driscoll [2003]: Occup Environ Health 9:206-217.

METHODS: We sought to reevaluate the AMSR data ourselves to understand how the company-sponsored research categorized the data.

RESULTS: In our re-analysis of the 78 brake-related folios in the AMSR, we determined that 57 were employed brake mechanics, 35 were employed brake mechanics with no other asbestos exposure besides brake work or repair, and 41 of these cases had no other asbestos exposure besides brake work or repair. Our classifications differed significantly from Kelsh et al.

CONCLUSIONS: We discuss how Kelsh et al. methodically reduced the relevant cases by following overly stringent criteria for inclusion. Am. J. Ind. Med. 60:152-162, 2017. © 2017 Wiley Periodicals, Inc.}, } @article {pmid28066892, year = {2017}, author = {Grosso, F and Croce, A and Trincheri, NF and Mariani, N and Libener, R and Degiovanni, D and Rinaudo, C}, title = {Asbestos fibres detected by scanning electron microscopy in the gallbladder of patients with malignant pleural mesothelioma (MPM).}, journal = {Journal of microscopy}, volume = {266}, number = {1}, pages = {48-54}, doi = {10.1111/jmi.12517}, pmid = {28066892}, issn = {1365-2818}, mesh = {Aged ; Asbestos/*analysis ; Female ; Gallbladder/*pathology ; Gallbladder Diseases/*pathology ; Histocytochemistry ; Humans ; Immunohistochemistry ; Lung Neoplasms/*complications ; Male ; Mesothelioma/*complications ; Mesothelioma, Malignant ; *Microscopy, Electron, Scanning ; Pleural Neoplasms/*complications ; Spectrometry, X-Ray Emission ; }, abstract = {Gallbladders from patients affected by both malignant pleural mesothelioma (MPM) and important gallbladder disorders were analyzed to verify the presence of asbestos fibres. Histological thin sections were analyzed by optical microscope and variable pressure scanning electron microscopy coupled with energy dispersive spectroscopy, allowing morphological and chemical characterization of each inorganic phase observed. Fibres of chrysotile and crocidolite, minerals regulated as asbestos, were identified. By immunohistochemical analysis, connective tissue was recognized as the incorporation site. These findings confirm that asbestos fibres can reach the gallbladders of patients with MPM, for whom the development of respiratory diseases confirms asbestos exposure.}, } @article {pmid28066660, year = {2016}, author = {Wang, XB and Yin, Y and Miao, Y and Eberhardt, R and Hou, G and Herth, FJ and Kang, J}, title = {Flex-rigid pleuroscopic biopsy with the SB knife Jr is a novel technique for diagnosis of malignant or benign fibrothorax.}, journal = {Journal of thoracic disease}, volume = {8}, number = {11}, pages = {E1555-E1559}, pmid = {28066660}, issn = {2072-1439}, abstract = {Diagnosing pleural effusion is challenging, especially in patients with malignant or benign fibrothorax, which is difficult to sample using standard flexible forceps (SFF) via flex-rigid pleuroscopy. An adequate sample is crucial for the differential diagnosis of malignant fibrothorax (malignant pleural mesothelioma, metastatic lung carcinoma, etc.) from benign fibrothorax (benign asbestos pleural disease, tuberculous pleuritis, etc.). Novel biopsy techniques are required in flex-rigid pleuroscopy to improve the sample size and quality. The SB knife Jr, which is a scissor forceps that uses a mono-pole high frequency, was developed to allow convenient and accurate resection of larger lesions during endoscopic dissection (ESD). Herein, we report two patients with fibrothorax who underwent a pleural biopsy using an SB knife Jr to investigate the potential use of this tool in flex-rigid pleuroscopy when pleural lesions are difficult to biopsy via SFF. The biopsies were successful, with sufficient size and quality for definitive diagnosis. We also successfully performed adhesiolysis with the SB knife Jr in one case, and adequate biopsies were conducted. No complications were observed. Electrosurgical biopsy with the SB knife Jr during flex-rigid pleuroscopy allowed us to obtain adequate samples for the diagnosis of malignant versus benign fibrothorax, which is usually not possible with SFF. The SB knife Jr also demonstrated a potential use for pleuropulmonary adhesions.}, } @article {pmid28056339, year = {2017}, author = {Thompson, JK and MacPherson, MB and Beuschel, SL and Shukla, A}, title = {Asbestos-Induced Mesothelial to Fibroblastic Transition Is Modulated by the Inflammasome.}, journal = {The American journal of pathology}, volume = {187}, number = {3}, pages = {665-678}, pmid = {28056339}, issn = {1525-2191}, support = {R01 ES021110/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Asbestos/*adverse effects ; Biomarkers/metabolism ; Caspase 1/metabolism ; Cell Line ; Cell Shape/genetics ; Epithelial Cells/metabolism/pathology ; Epithelium/metabolism/*pathology ; Fibroblasts/metabolism/*pathology ; Gene Expression Profiling ; Gene Expression Regulation ; Humans ; Inflammasomes/*metabolism ; Interleukin-1beta/metabolism ; Mice ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Peritoneum/metabolism/pathology ; Signal Transduction/genetics ; }, abstract = {Despite the causal relationship established between malignant mesothelioma (MM) and asbestos exposure, the exact mechanism by which asbestos induces this neoplasm and other asbestos-related diseases is still not well understood. MM is characterized by chronic inflammation, which is believed to play an intrinsic role in the origin of this disease. We recently found that asbestos activates the nod-like receptor family member containing a pyrin domain 3 (NLRP3) inflammasome in a protracted manner, leading to an up-regulation of IL-1β and IL-18 production in human mesothelial cells. Combined with biopersistence of asbestos fibers, we hypothesize that this creates an environment of chronic IL-1β signaling in human mesothelial cells, which may promote mesothelial to fibroblastic transition (MFT) in an NLRP3-dependent manner. Using a series of experiments, we found that asbestos induces a fibroblastic transition of mesothelial cells with a gain of mesenchymal markers (vimentin and N-cadherin), whereas epithelial markers, such as E-cadherin, are down-regulated. Use of siRNA against NLRP3, recombinant IL-1β, and IL-1 receptor antagonist confirmed the role of NLRP3 inflammasome-dependent IL-1β in the process. In vivo studies using wild-type and various inflammasome component knockout mice also revealed the process of asbestos-induced mesothelial to fibroblastic transition and its amelioration in caspase-1 knockout mice. Taken together, our data are the first to suggest that asbestos induces mesothelial to fibroblastic transition in an inflammasome-dependent manner.}, } @article {pmid28054314, year = {2017}, author = {Plönes, T and Fischer, M and Höhne, K and Sato, H and Müller-Quernheim, J and Zissel, G}, title = {Turning back the Wheel: Inducing Mesenchymal to Epithelial Transition via Wilms Tumor 1 Knockdown in Human Mesothelioma Cell Lines to Influence Proliferation, Invasiveness, and Chemotaxis.}, journal = {Pathology oncology research : POR}, volume = {23}, number = {4}, pages = {723-730}, pmid = {28054314}, issn = {1532-2807}, mesh = {Cell Line, Tumor ; Cell Proliferation/genetics ; Chemotaxis/genetics ; Drug Resistance, Neoplasm/genetics ; Gene Knockdown Techniques ; Humans ; Lung Neoplasms/*genetics/*pathology ; Mesothelioma/*genetics/*pathology ; Mesothelioma, Malignant ; Neoplasm Invasiveness/genetics ; Pleural Neoplasms/*genetics/*pathology ; WT1 Proteins/*genetics ; }, abstract = {Malignant pleural mesothelioma (MPM) is a highly aggressive tumor that arises from the surface of the pleura and is associated with a history of asbestos exposure. The tumor is characterized by a strong local invasiveness and a poor response to any single modality therapy. Therefore clinical outcome of patients with MPM is poor and median survival time of untreated patients with MPM is 7 months from initial diagnosis. The Wilms Tumor Protein 1 (WT1) is a transcription factor which is highly expressed by MPM and is involved in cellular development and survival. We evaluated the role of WT1 in two human MPM cell lines (MSTO and H2052) expressing high levels of WT1. We performed a knockdown of WT1 using siRNA. Knockdown of WT1 was confirmed by Westernblotting. After knockdown of WT1 we investigated the effect on proliferation, chemoresistance, chemotaxis and migration. We could demonstrate that knockdown of WT1 suppresses chemoresistance in both cell lines compared with control (scrambled siRNA). Additionally, WT1 knockdown reduces proliferation, chemotaxis and invasiveness of mesothelioma cell lines. WT1 reduces malignancy of malignant mesothelioma cell lines and might be a new molecular target in mesothelioma therapy. Further investigations are needed to discover the mechanisms of chemoresistance depending on WT1.}, } @article {pmid28051835, year = {2016}, author = {Fallahi, P and Ragusa, F}, title = {Mesothelioma and interferon-γ-dependent chemokine IP-10.}, journal = {La Clinica terapeutica}, volume = {167}, number = {6}, pages = {e192-e197}, pmid = {28051835}, issn = {1972-6007}, mesh = {Adult ; Animals ; Apoptosis/drug effects ; Asbestos/adverse effects ; Asbestosis/immunology ; CD8-Positive T-Lymphocytes ; Chemokine CXCL10/*metabolism ; Female ; Humans ; Interferon-gamma/metabolism ; Lung Neoplasms/*immunology ; Male ; Mesothelioma/*immunology ; Mesothelioma, Malignant ; Rats ; Receptors, CXCR3 ; }, abstract = {Recently it has been shown that interferon (IFN)-γ plays an important role in mesothelioma, mediated by the main IFN-γ dependent chemokines, chemokine (C-X-C motif) ligand (CXCL)10/IFN-γ- induced protein 10 (IP-10). IP-10 is up-regulated in malignant mesothelioma (MM), suggesting a relationship with development of these tumors. Nanoparticles containing nickel, that increase the risk for pleural diseases, induced increased levels of IP-10 in rat pleural mesothelial cells. Chemokine (C-X-C motif) receptor (CXCR)3 expression in CD4(+) T cells from pleural plaques and MMs was significantly decreased compared with that from healthy donors suggesting that CXCR3, IFN-γ, and IP-10 may be candidates to detect and monitor disease status. In a patient with asbestos-related malignant pleural mesothelioma the oncolytic adenovirus (ONCOS-102) induced prominent infiltration of CD8(+) lymphocytes to tumor, marked induction of systemic antitumor CD8(+) T-cells and expression of IP-10. Furthermore, increased IP- 10 concentrations were observed in the sera of the asbestos-exposed workers and were associated with the severity of asbestos-related diseases. These findings suggest that IP-10 chemokine may have a prognostic role in the progression of asbestos-related diseases and could be used for the health surveillance of either workers with an occupational history of asbestos exposure or patients affected by nonmalignant asbestos-related diseases.}, } @article {pmid28050426, year = {2016}, author = {Batahar, SA and Ouradi, O and Elidrissi, S and Amro, L}, title = {Pleural Mesothelioma with No Asbestos Exposure: A Case Report.}, journal = {Journal of clinical and diagnostic research : JCDR}, volume = {10}, number = {11}, pages = {OD07-OD08}, pmid = {28050426}, issn = {2249-782X}, abstract = {Malignant Pleural Mesothelioma (MPM) is the primary malignant tumour of the pleura. It is highly aggressive and linked to the exposure to asbestos fibers. The prognosis of this cancer is bad with a median of survival around 12 months. The diagnosis of pleural mesothelioma is often done at an advanced stage of the disease because of the lack of specific clinical and radiological signs differentiating it from any malignant pleural effusion. The absence of an explicit asbestos exposure is another diagnosis problem. We report the case of a 60-year-old patient without any prior exposure to asbestos who presented for pleural effusion and a nodular thickening of the pleura on the CT scan. The diagnosis of MPM was confirmed after pathology study of the biopsies obtained by video assisted thoracoscopy.}, } @article {pmid28038708, year = {2017}, author = {Wu, D and Hiroshima, K and Yusa, T and Ozaki, D and Koh, E and Sekine, Y and Matsumoto, S and Nabeshima, K and Sato, A and Tsujimura, T and Yamakawa, H and Tada, Y and Shimada, H and Tagawa, M}, title = {Usefulness of p16/CDKN2A fluorescence in situ hybridization and BAP1 immunohistochemistry for the diagnosis of biphasic mesothelioma.}, journal = {Annals of diagnostic pathology}, volume = {26}, number = {}, pages = {31-37}, doi = {10.1016/j.anndiagpath.2016.10.010}, pmid = {28038708}, issn = {1532-8198}, mesh = {Aged ; Biomarkers, Tumor/analysis ; Cyclin-Dependent Kinase Inhibitor p16 ; Cyclin-Dependent Kinase Inhibitor p18/*genetics ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry/methods ; In Situ Hybridization, Fluorescence/methods ; Male ; Mesothelioma/*diagnosis/*genetics ; Middle Aged ; Pleural Neoplasms/*diagnosis/genetics ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {Malignant mesothelioma is a highly aggressive neoplasm, and the histologic subtype is one of the most reliable prognostic factors. Some biphasic mesotheliomas are difficult to distinguish from epithelioid mesotheliomas with atypical fibrous stroma. The aim of this study was to analyze p16/CDKN2A deletions in mesotheliomas by fluorescence in situ hybridization (FISH) and BAP1 immunohistochemistry to evaluate their potential role in the diagnosis of biphasic mesothelioma. We collected 38 cases of pleural mesotheliomas. The results of this study clearly distinguished 29 cases of biphasic mesothelioma from 9 cases of epithelioid mesothelioma. The proportion of biphasic mesotheliomas with homozygous deletions of p16/CDKN2A in total was 96.6% (28/29). Homozygous deletion of p16/CDKN2A was observed in 18 (94.7%) of 19 biphasic mesotheliomas with 100% concordance of the p16/CDKN2A deletion status between the epithelioid and sarcomatoid components in each case. Homozygous deletion of the p16/CDKN2A was observed in 7 (77.8%) of 9 epithelioid mesotheliomas but not in fibrous stroma. BAP1 loss was observed in 5 (38.5%) of 13 biphasic mesotheliomas and in both epithelioid and sarcomatoid components. BAP1 loss was observed in 5 (62.5%) of 8 epithelioid mesotheliomas but not in fibrous stroma. Homozygous deletion of p16/CDKN2A is common in biphasic mesotheliomas, and the analysis of only one component of mesothelioma is sufficient to show that the tumor is malignant. However, compared with histology alone, FISH analysis of the p16/CDKN2A status and BAP1 immunohistochemistry in the spindled mesothelium provide a more objective means to differentiate between biphasic mesothelioma and epithelioid mesothelioma with atypical stromal cells.}, } @article {pmid28034829, year = {2017}, author = {Leblay, N and Leprêtre, F and Le Stang, N and Gautier-Stein, A and Villeneuve, L and Isaac, S and Maillet, D and Galateau-Sallé, F and Villenet, C and Sebda, S and Goracci, A and Byrnes, G and McKay, JD and Figeac, M and Glehen, O and Gilly, FN and Foll, M and Fernandez-Cuesta, L and Brevet, M}, title = {BAP1 Is Altered by Copy Number Loss, Mutation, and/or Loss of Protein Expression in More Than 70% of Malignant Peritoneal Mesotheliomas.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {12}, number = {4}, pages = {724-733}, doi = {10.1016/j.jtho.2016.12.019}, pmid = {28034829}, issn = {1556-1380}, support = {001/WHO_/World Health Organization/International ; }, mesh = {Adolescent ; Adult ; Aged ; Biomarkers, Tumor/genetics/metabolism ; *DNA Copy Number Variations ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/genetics/metabolism/*pathology ; Male ; Mesothelioma/genetics/metabolism/*pathology ; Mesothelioma, Malignant ; Middle Aged ; *Mutation ; Neoplasm Staging ; Peritoneal Neoplasms/genetics/metabolism/*pathology ; Pleural Neoplasms/genetics/metabolism/*pathology ; Prognosis ; Survival Rate ; Tumor Suppressor Proteins/*genetics/*metabolism ; Ubiquitin Thiolesterase/*genetics/*metabolism ; Young Adult ; }, abstract = {INTRODUCTION: Malignant mesothelioma is a deadly disease that is strongly associated with asbestos exposure. Peritoneal mesotheliomas account for 10% of all the cases. BRCA1 associated protein 1 (BAP1) is a deubiquitinating hydrolase that plays a key role in various cellular processes. Germline and somatic inactivation of BRCA1 associated protein 1 gene (BAP1) is frequent in pleural mesothelioma; however, little is known about its status in peritoneal mesothelioma.

METHODS: Taking advantage of the extensive French National Network for the Diagnosis of Malignant Pleural Mesothelioma and Rare Peritoneal Tumors and the French National Network for the Treatment of Rare Peritoneal Surface Malignancies, we collected biological material and clinical and epidemiological data for 46 patients with peritoneal mesothelioma. The status of BAP1 was evaluated at the mutational and protein expression levels and combined with our previous data on copy number alterations assessed in the same samples.

RESULTS: We detected mutations in 32% of the malignant peritoneal mesotheliomas analyzed. In addition, we have previously reported that copy number losses occurred in 42% of the samples included in this series. Overall, 73% of the malignant peritoneal mesotheliomas analyzed carried at least one inactivated BAP1 allele, but only 57% had a complete loss of its protein nuclear expression. Better overall survival was observed for patients with BAP1 mutations (p = 0.04), protein expression loss (p = 0.016), or at least one of these alterations (p = 0.007) independently of tumor histological subtype, age, and sex.

CONCLUSIONS: As in pleural mesothelioma, inactivation of BAP1 is frequent in peritoneal mesotheliomas. We found that BAP1 protein nuclear expression is a good prognostic factor and a more reliable marker for the complete loss of BAP1 activity than mutation or copy number loss.}, } @article {pmid28026144, year = {2018}, author = {Paliogiannis, P and Putzu, C and Ginesu, GC and Cossu, ML and Feo, CF and Attene, F and Scognamillo, F and Nonnis, R and Cossu, A and Palmieri, G and Pirina, P and Fois, A}, title = {Deciduoid mesothelioma of the thorax: A comprehensive review of the scientific literature.}, journal = {The clinical respiratory journal}, volume = {12}, number = {3}, pages = {848-856}, doi = {10.1111/crj.12599}, pmid = {28026144}, issn = {1752-699X}, mesh = {Adolescent ; Adult ; Aged ; Asbestos/adverse effects ; Chest Pain/etiology ; Cough/etiology ; Deciduoma/*pathology ; Environmental Exposure/adverse effects ; Female ; Humans ; Lung Neoplasms/diagnostic imaging/metabolism/*pathology ; Male ; Mesothelioma/diagnostic imaging/metabolism/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Pleura/diagnostic imaging/*pathology ; Pleural Neoplasms/diagnostic imaging/*pathology ; Prognosis ; Radiography, Thoracic/methods ; Thoracic Neoplasms/diagnostic imaging/pathology ; Tomography, X-Ray Computed/methods ; Weight Loss ; Young Adult ; }, abstract = {OBJECTIVE: Deciduoid mesothelioma is a rare variant of malignant epithelioid mesothelioma. It often involves the peritoneum, but also thoracic cases have been reported. The aim of the present review is to describe the demographic, clinical, radiological, and pathological features of such a rare variant of thoracic mesothelioma, and the state of the art regarding the therapeutic approaches currently available.

DATA SOURCE: English-language articles published from 1985 to June 2016, and related to thoracic deciduoid mesothelioma cases were retrieved using the Pubmed database.

STUDY SELECTION: The search terms were "mesothelioma," "thoracic mesothelioma," "epithelial mesothelioma," "pleural mesothelioma," and "deciduoid mesothelioma."

RESULTS: Forty-four cases included in 16 articles, published in the period under investigation, were analyzed in detail.

CONCLUSIONS: The mean age of the patients was 63 years, and the male to female ratio 1.7:1. Approximately 58% had exposure to asbestos, and 73% had a smoking history; familiarity was rarely reported. The most common anatomical site of origin was the right pleura, and the most frequent clinical manifestations were chest pain, dyspnea, cough, and weight loss. Thoracic X-ray and computed tomography were the imaging techniques most employed for diagnosis and surgical planning. The pathological diagnosis was obtained by examination of surgical or biopsy specimens in most cases. The best treatment strategy of deciduoid mesothelioma is a matter of debate; nevertheless a multidisciplinary approach is currently the best option for the choice of the adequate therapeutic scheme.}, } @article {pmid28025765, year = {2017}, author = {Lehnert, M and Kraywinkel, K and Heinze, E and Wiethege, T and Johnen, G and Fiebig, J and Brüning, T and Taeger, D}, title = {Incidence of malignant mesothelioma in Germany 2009-2013.}, journal = {Cancer causes & control : CCC}, volume = {28}, number = {2}, pages = {97-105}, doi = {10.1007/s10552-016-0838-y}, pmid = {28025765}, issn = {1573-7225}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/toxicity ; Female ; Germany/epidemiology ; Humans ; Incidence ; Lung Neoplasms/*epidemiology/etiology ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Exposure/adverse effects ; Registries ; }, abstract = {PURPOSE: The malignant mesothelioma is a rare malignancy and mainly caused by occupational exposure to asbestos. German cancer registries are providing a national database to investigate temporal and regional patterns of mesothelioma incidence. These may be of interest for healthcare planning and for surveillance programs aiming at the formerly exposed workforce.

METHODS: We analyzed population-based incidence data of malignant mesothelioma by site, type, sex, age, as well as district and state of patient's residence. Age-standardized incidence rates (AIRs40+) were calculated according to the European standard population truncated to the age of 40 years and older. We present rates at national, state, and district level and trends of incidence of northern states of Germany.

RESULTS: In total, 7,547 malignant mesotheliomas were reported to German cancer registries diagnosed between 2009 and 2013-90% located to the pleura. On average, 1,198 men and 312 women were affected each year. We estimated AIR40+ of 4.77 in 100,000 German men and 0.98 in 100,000 German women. Regional clusters were predominantly located to the seaports of West Germany. The highest regional AIR40+ was 20 per 100,000 men. Corresponding rates in northeast Germany were between 2 and 4 per 100,000 men.

CONCLUSION: Regional clusters of high incidence indicate districts with former shipyards and steel industry, but predominantly in the western part of Germany. The West-to-East difference corresponds to patterns of mortality. Twenty years after banning asbestos in Germany, Bremen and Hamburg are presenting the highest mesothelioma incidence but show steadily decreasing trends.}, } @article {pmid28013367, year = {2017}, author = {MacPherson, M and Westbom, C and Kogan, H and Shukla, A}, title = {Actin polymerization plays a significant role in asbestos-induced inflammasome activation in mesothelial cells in vitro.}, journal = {Histochemistry and cell biology}, volume = {147}, number = {5}, pages = {595-604}, pmid = {28013367}, issn = {1432-119X}, support = {R01 ES021110/ES/NIEHS NIH HHS/United States ; S10 RR019246/RR/NCRR NIH HHS/United States ; }, mesh = {Actins/antagonists & inhibitors/*metabolism ; Asbestos/*adverse effects/antagonists & inhibitors ; Cell Survival/drug effects ; Cells, Cultured ; Cytochalasin D/pharmacology ; Dose-Response Relationship, Drug ; Epithelial Cells/*drug effects/metabolism ; Humans ; Inflammasomes/*drug effects/metabolism ; Polymerization/drug effects ; Structure-Activity Relationship ; }, abstract = {Asbestos exposure leads to malignant mesothelioma (MM), a deadly neoplasm of mesothelial cells of various locations. Although there is no doubt about the role of asbestos in MM tumorigenesis, mechanisms are still not well explored. Recently, our group demonstrated that asbestos causes inflammasome priming and activation in mesothelial cells, which in part is dependent on oxidative stress. Our current study sheds light on yet another mechanism of inflammasome activation by asbestos. Here we show the role of actin polymerization in asbestos-induced activation of the nod-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome. Using human mesothelial cells, we first demonstrate that asbestos and carbon nanotubes induced caspase-1 activation and high-mobility group box 1, interleukin 1 beta and interleukin 18 secretion was blocked by Cytochalasin D (Cyto D) an actin polymerization inhibitor. Next, to understand the mechanism, we assessed whether phagocytosis of fibers by mesothelial cells is affected by actin polymerization inhibition. Transmission electron microscopy showed the inhibition of fiber uptake by mesothelial cells in the presence of Cyto D. Furthermore, localization of components of the inflammasome, apoptotic speck-like protein containing a CARD domain (ASC) and NLRP3, to the perinuclear space in mitochondria or endoplasmic reticulum in response to fiber exposure was also interrupted in the presence of Cyto D. Taken together, our studies suggest that actin polymerization plays important roles in inflammasome activation by fibers via regulation of phagocytosis and/or spatial localization of inflammasome components.}, } @article {pmid28007630, year = {2017}, author = {Guo, Z and Carbone, M and Zhang, X and Su, D and Sun, W and Lou, J and Gao, Z and Shao, D and Chen, J and Zhang, G and Hu, J and Chen, K and Wang, F and Pass, HI and Yu, H and Napolitano, A and Yang, H and Mao, W}, title = {Improving the Accuracy of Mesothelioma Diagnosis in China.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {12}, number = {4}, pages = {714-723}, pmid = {28007630}, issn = {1556-1380}, support = {P30 CA071789/CA/NCI NIH HHS/United States ; R01 CA160715/CA/NCI NIH HHS/United States ; R01 CA198138/CA/NCI NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; }, mesh = {Adenocarcinoma/diagnosis/epidemiology ; Adult ; Aged ; Biomarkers, Tumor/analysis ; Carcinoma, Squamous Cell/diagnosis/epidemiology ; Case-Control Studies ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/*diagnosis/epidemiology ; Male ; Mesothelioma/*diagnosis/epidemiology ; Mesothelioma, Malignant ; Middle Aged ; Neoplasm Staging ; Peritoneal Neoplasms/*diagnosis/epidemiology ; Pleural Neoplasms/*diagnosis/epidemiology ; Prognosis ; Young Adult ; }, abstract = {INTRODUCTION: In the Western world, malignant mesothelioma (MM) is most prevalent in the pleura of older males who have been professionally exposed to asbestos. Information about MM from rapidly industrializing countries such as China is minimal. There is concern that a proportion of MM diagnoses in China may be incorrect because most Chinese physicians do not have experience diagnosing this rare cancer. We recently reported an unusually high incidence of peritoneal MM among eastern Chinese female patients. Here, we review the accuracy of MM diagnoses in China and provide suggestions to improve the accuracy of diagnosis.

METHODS: We reviewed 92 pathological diagnosis of MM in 2002-2015 from two reference centers in the province of Zhejiang in eastern China. We performed a large set of immunohistochemistry analyses to increase the reliability of the diagnosis.

RESULTS: We confirmed the MM diagnosis in 12 of 34 of the pleural tumors (35.3%), in 38 of 56 of the peritoneal tumors (67.9%), and in two of two of the MMs of the tunica vaginalis (100%). MMs were characterized by tumor cells showing nuclear Wilms tumor 1 and calretinin staining and by strong membranous staining for cytokeratin CAM5.2. The results of staining for the epithelial markers carcinoembryonic antigen, thyroid transcription factor-1, MOC31, BerEP4, p63, p40, paired box 8, ER and PR were negative. BRCA1 associated protein 1 nuclear staining was lost in percentages similar to what has been reported for samples from Western countries.

CONCLUSIONS: Our findings suggest that MM-especially in its pleural localization-is often misdiagnosed in eastern China. Identifying pitfalls and possible solutions in the pathological diagnosis of MM will affect both the standard of care and research in China.}, } @article {pmid28007619, year = {2017}, author = {Creaney, J and Robinson, BWS}, title = {Malignant Mesothelioma Biomarkers: From Discovery to Use in Clinical Practice for Diagnosis, Monitoring, Screening, and Treatment.}, journal = {Chest}, volume = {152}, number = {1}, pages = {143-149}, doi = {10.1016/j.chest.2016.12.004}, pmid = {28007619}, issn = {1931-3543}, mesh = {Biomarkers, Tumor/blood ; Early Detection of Cancer/*methods ; GPI-Linked Proteins/*blood ; Humans ; *Lung Neoplasms/blood/pathology/therapy ; Mesothelin ; *Mesothelioma/blood/pathology/therapy ; Mesothelioma, Malignant ; *Pleural Neoplasms/blood/pathology/therapy ; Prognosis ; }, abstract = {Malignant pleural mesothelioma is a highly aggressive tumor associated with asbestos exposure. There are few effective treatment options for mesothelioma, and patients have a very poor prognosis with a median survival of < 12 months from diagnosis. Biomarkers have been proposed as a cost-effective means of cancer management, and the search for a mesothelioma biomarker has been ongoing for the last 30 years. Many traditional soluble (glyco)protein biomarkers have been evaluated over this time, and an ever-increasing list of new biomarkers, including messenger RNA, DNA, microRNA, and antibodies, is being reported from biomarker discovery projects. To date, soluble mesothelin is the only tumor biomarker to receive US Food and Drug Administration approval for clinical use in mesothelioma. Mesothelin is a glycoprotein normally expressed on the surface of mesothelial cells, and in the cancerous state it can be present in circulation. Mesothelin has a limited expression on normal, nonmalignant tissue and is thus an attractive therapeutic target for mesothelin-positive tumors. In this review we will focus on the discovery and clinical usages of mesothelin and provide an update on other mesothelioma biomarkers and show how such biomarker studies might impact on the management of this deadly tumor in the future.}, } @article {pmid28002541, year = {2016}, author = {Raşcu, A and Naghi, E and OŢelea, MR and NiŢu, FM and Arghir, OC}, title = {Distinction between mesothelioma and lung adenocarcinoma based on immunohistochemistry in a patient with asbestos bodies in bronchoalveolar fluid - case report.}, journal = {Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie}, volume = {57}, number = {3}, pages = {1171-1174}, pmid = {28002541}, issn = {2066-8279}, mesh = {Adenocarcinoma/*immunology/pathology ; Adenocarcinoma of Lung ; Asbestosis/pathology ; Bronchoalveolar Lavage Fluid/*cytology ; Humans ; Immunohistochemistry ; Lung Neoplasms/*immunology/pathology ; Male ; Mesothelioma/*immunology/pathology ; Middle Aged ; }, abstract = {Asbestos is a mineral-mined form the rocks, consisting in amosite (brown asbestos), crocidolite (blue asbestos) and÷or chrysotile (white asbestos) used in many industries. Researches about the exposure to asbestos dust and asbestosis related diseases started almost a century ago. The first case report of fatal asbestosis disease was published in 1906, in England, by Dr. Hubert Montague Murray. A decade after, asbestos "curious bodies" were firstly described in the lung tissue by Cooke (1926) and McDonald (1927). Occupational exposure to asbestos is now regulated in Romania, but past exposure is still a cause of asbestosis-related diseases (ARDs), including lung cancer. A peculiar association between a lung adenocarcinoma, a previously healed pulmonary tuberculosis (PTB) disease, is reported in a 61-year-old nonsmoker white man, a former factory worker with 29 years of occupational exposure history to cement and asbestos fibers. The positive diagnosis of asbestos exposure was facilitated by asbestos bodies determined in bronchoalveolar lavage fluid. The main purpose of this case report is to describe the development of a right pleural effusion which was not revelatory for a mesothelioma but for an adenocarcinoma of the lung. An accurate morphologic and immunohistochemistry assessment of a pleural biopsy sample excluded mesothelioma and was crucial in the positive diagnosis of adenocarcinoma. In conclusion, unilateral paraneoplastic pleural effusion in a nonsmoker male with occupational exposure to asbestosis fibers was suggestive for adenocarcinoma related asbestosis of the lung. Lung cancer and malignant pleural exudate developed after a long latency cumulative retention time of asbestos fibers.}, } @article {pmid27993826, year = {2016}, author = {Yildiz, H and Andreea, SI and Hoton, D and Yombi, JC}, title = {Minimal change disease associated with malignant pleural mesothelioma: case report and review of the literature.}, journal = {BMJ case reports}, volume = {2016}, number = {}, pages = {}, pmid = {27993826}, issn = {1757-790X}, mesh = {Aged ; Biopsy ; Fatal Outcome ; Humans ; Kidney/*diagnostic imaging ; Lung Neoplasms/complications/*diagnosis ; Male ; Mesothelioma/complications/*diagnosis ; Mesothelioma, Malignant ; Nephrosis, Lipoid/complications/*diagnosis ; Pleura/*diagnostic imaging ; Pleural Neoplasms/complications/*diagnosis ; Positron-Emission Tomography ; Tomography, X-Ray Computed ; }, abstract = {A 77-year-old man with a history of asbestos exposure was admitted to our internal medicine division for generalised weakness, fatigue, loss of weight, night sweats and difficulty for breathing since 3 months. Clinical examination revealed left fine crackles and bilateral leg oedema. Blood test showed elevated C reactive protein level at 142 mg/L, lactate dehydrogenase level at 421 UI, creatinine level at 5.75 mg/dL. Serum albumin level at 30 g/L, urinalysis showed significant proteinuria at 6.4 g/L. Chest X-ray showed left pleural effusion. Renal ultrasonography was normal. Thoracic CT and positron emission tomography showed mediastinal enlargement with lymphadenopathies and left pleural effusion and thickening. A pleural biopsy showed features compatible with malignant epithelioid mesothelioma. Renal biopsy showed minimal change disease and acute tubular necrosis. A diagnosis of malignant mesothelioma associated with minimal change disease and acute tubular necrosis secondary was then made. Given the poor general condition, palliative care was initiated and the patient died from respiratory failure 3 months later.}, } @article {pmid27980793, year = {2016}, author = {Kang, DM and Kim, JE and Lee, YJ and Lee, HH and Lee, CY and Moon, SJ and Kang, MS}, title = {Environmental health centers for asbestos and their health impact surveys and activities.}, journal = {Annals of occupational and environmental medicine}, volume = {28}, number = {}, pages = {68}, pmid = {27980793}, issn = {2052-4374}, abstract = {In 2009, Korea banned the import, transport, and use of asbestos, and the Asbestos Injury Relief Act (AIRA) was promulgated in 2011. Two environmental health centers for asbestos (EHCA), including Pusan National University Yangsan Hospital (PNUYH) and SoonChunHyang University Cheonan Hospital (SCHUCH), were adapted to find environmental asbestos-related diseases (ARDs) and to support the purposes of AIRA. EHCA conducted a health impact survey (HIS) on persons who resided or reside near asbestos factories or mines. A total of 13,433 persons have taken screening examinations in PNUYH EHCA, and 623 persons (4.6%) have had secondary examinations. Of the 21,014 persons who had screening examinations in SCHUCH EHCA, 2490 persons (11.8%) had secondary examinations. Some of those who tested positive for ARDs through HISs filed applications for the asbestos victims' medical pocketbook (AVMP). Approximately 116 and 612 persons received AVMPs as a result of PNUYH and SCHUCH examinees, respectively. EHCAs have conducted HISs, public relations, and education for asbestos victims, ordinary citizens, and physicians. As HISs are based on voluntary participation, they does not monitor high-risk groups. Active surveillance focusing on high-risk groups has been blocked by the personal information protection act. Although important work has been performed in finding environmental asbestos victims and increasing public awareness on asbestos, it is necessary to improve the current system and registration.}, } @article {pmid27979465, year = {2017}, author = {Siegert, CJ and Fisichella, PM and Moseley, JM and Shoni, M and Lebenthal, A}, title = {Open access phone triage for veterans with suspected malignant pleural mesothelioma.}, journal = {The Journal of surgical research}, volume = {207}, number = {}, pages = {108-114}, doi = {10.1016/j.jss.2016.08.031}, pmid = {27979465}, issn = {1095-8673}, mesh = {Aged ; Boston ; Feasibility Studies ; Health Services Accessibility/*statistics & numerical data ; Humans ; Male ; Mesothelioma/*diagnosis ; Pleural Neoplasms/*diagnosis ; Referral and Consultation/statistics & numerical data ; Retrospective Studies ; Telemedicine/*methods/statistics & numerical data ; Telephone ; Triage/*methods/statistics & numerical data ; United States ; United States Department of Veterans Affairs ; *Veterans Health ; }, abstract = {BACKGROUND: Phone triaging patients with suspected malignant pleural mesothelioma (MPM) within the Veterans Healthcare Administration (VHA) system offers a model for rapid, expert guided evaluation for patients with rare and treatable diseases within a national integrated healthcare system. To assess feasibility of national open access telephone triage using evidence-based treatment recommendations for patients with MPM, measure timelines of the triage and referral process and record the impact on "intent to treat" for patients using our service.

METHODS: A retrospective study. The main outcome measures were: (1) ability to perform long distance phone triage, (2) to assess the speed of access to a mesothelioma surgical specialist for patients throughout the entire VHA, and (3) to determine if access to a specialist would alter the plan of care.

RESULTS: Sixty veterans were screened by our phone triage program, 38 traveled an average of 997 miles to VA Boston Healthcare system. On average, 14 d elapsed from initial phone contact until the patient was physically evaluated in our general thoracic clinic in Boston. The treatment plan was altered for 71% of patients evaluated at VA Boston Healthcare system based on 2012 International Mesothelioma Interest Group guidelines.

CONCLUSIONS: Our initial experience demonstrates that in-network centralized care for Veterans with MPM is feasible within the VHA. National open access phone triage improves access to expert surgical advice and can be delivered in a timely manner for Veterans using our service. Guideline-based treatment recommendations ("intent to treat") changed the therapeutic course for the majority of patients who used our service.}, } @article {pmid27941034, year = {2017}, author = {Ferrante, D and Mirabelli, D and Tunesi, S and Terracini, B and Magnani, C}, title = {Pleural mesothelioma and asbestos exposure: a case-control study with quantitative risk assessment-response to Marsh and Benson's letter.}, journal = {Occupational and environmental medicine}, volume = {74}, number = {2}, pages = {157-158}, doi = {10.1136/oemed-2016-104091}, pmid = {27941034}, issn = {1470-7926}, mesh = {*Asbestos ; Case-Control Studies ; Humans ; Mesothelioma ; Occupational Exposure ; Pleura ; *Pleural Neoplasms ; Risk Assessment ; }, } @article {pmid27941033, year = {2017}, author = {Marsh, GM and Benson, SM}, title = {Response to: 'Pleural mesothelioma and occupational and non-occupational asbestos exposure: a case-control study with quantitative risk assessment' by Ferrante et al.}, journal = {Occupational and environmental medicine}, volume = {74}, number = {2}, pages = {156-157}, doi = {10.1136/oemed-2016-104002}, pmid = {27941033}, issn = {1470-7926}, mesh = {*Asbestos ; Case-Control Studies ; Humans ; Mesothelioma ; Occupational Exposure ; *Pleural Neoplasms ; Risk Assessment ; }, } @article {pmid27919155, year = {2016}, author = {Di Ciaula, A and Gennaro, V}, title = {[Possible health risks from asbestos in drinking water].}, journal = {Epidemiologia e prevenzione}, volume = {40}, number = {6}, pages = {472-475}, doi = {10.19191/EP16.6.P472.129}, pmid = {27919155}, issn = {1120-9763}, mesh = {Animals ; Asbestos/*adverse effects ; *Carcinogens ; Drinking Water/*analysis ; Environmental Exposure/*adverse effects ; *Gastrointestinal Neoplasms/epidemiology/etiology/prevention & control ; Humans ; Italy/epidemiology ; Mesothelioma/epidemiology/etiology/prevention & control ; Mineral Fibers/adverse effects ; Pleural Neoplasms/epidemiology/etiology/prevention & control ; Risk Assessment ; Risk Factors ; Time Factors ; Water Pollutants, Chemical/*toxicity ; }, abstract = {The recent finding of asbestos fibres in drinking water (up to 700.000 fibres/litres) in Tuscany (Central Italy) leads to concerns about health risks in exposed communities. Exposure to asbestos has been linked with cancer at several levels of the gastrointestinal tract, and it has been documented, in an animal model, a direct cytotoxic effect of asbestos fibres on the ileum. It has been recently described a possible link between asbestos and intrahepatic cholangiocarcinoma, and asbestos fibres have been detected in humans in histological samples from colon cancer and in gallbladder bile. Taken together, these findings suggest the possibility of an enterohepatic translocation of asbestos fibres, alternative to lymphatic translocation from lungs. In animal models, asbestos fibres ingested with drinking water act as a co-carcinogen in the presence of benzo(a) pyrene and, according to the International Agency for Research on Cancer (IARC), there is evidence pointing to a causal effect of ingested asbestos on gastric and colorectal cancer. The risk seems to be proportional to the concentration of ingested fibres, to the extent of individual water consumption, to exposure timing, and to the possible exposure to other toxics (i.e., benzo(a)pyrene). Furthermore, the exposure to asbestos by ingestion could explain the epidemiological finding of mesothelioma in subjects certainly unexposed by inhalation. In conclusion, several findings suggest that health risks from asbestos could not exclusively derive from inhalation of fibres. Health hazards might also be present after ingestion, mainly after daily ingestion of drinking water for long periods. In Italy, a systemic assessment of the presence of asbestos fibres in drinking water is still lacking, although asbestos-coated pipelines are widely diffused and still operating. Despite the fact that the existence of a threshold level for health risks linked to the presence of asbestos in drinking water is still under debate, the precautionary principle should impose all possible efforts in order to revise health policies concerning this topic, and a systematic monitoring of drinking water to quantify the presence of asbestos is certainly needed in all regions. Further epidemiological studies aimed to the identification of exposed communities and to an adequate health risk assessment in their specific geographical areas are urgently needed.}, } @article {pmid27918607, year = {2017}, author = {Mao, W and Zhang, X and Guo, Z and Gao, Z and Pass, HI and Yang, H and Carbone, M}, title = {Association of Asbestos Exposure With Malignant Mesothelioma Incidence in Eastern China.}, journal = {JAMA oncology}, volume = {3}, number = {4}, pages = {562-564}, pmid = {27918607}, issn = {2374-2445}, support = {P30 CA071789/CA/NCI NIH HHS/United States ; R01 CA160715/CA/NCI NIH HHS/United States ; R01 CA198138/CA/NCI NIH HHS/United States ; }, mesh = {Asbestos/*toxicity ; China/epidemiology ; Female ; Humans ; Lung Neoplasms/*epidemiology/*etiology/pathology ; Male ; Mesothelioma/*epidemiology/*etiology/pathology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/*adverse effects/statistics & numerical data ; }, } @article {pmid27914752, year = {2017}, author = {Cruz, MJ and Curull, V and Pijuan, L and Álvarez-Simón, D and Sánchez-Font, A and de Gracia, J and Culebras, M and Ferrer, J}, title = {Utility of Bronchoalveolar Lavage for the Diagnosis of Asbestos-Related Diseases.}, journal = {Archivos de bronconeumologia}, volume = {53}, number = {6}, pages = {318-323}, doi = {10.1016/j.arbres.2016.08.016}, pmid = {27914752}, issn = {1579-2129}, mesh = {Aged ; Asbestos/adverse effects/*analysis ; Asbestosis/diagnosis/etiology/pathology ; Bronchoalveolar Lavage Fluid/*chemistry ; Bronchoscopy ; Carcinoma/chemistry/diagnosis/etiology/pathology ; Female ; Humans ; Lung Diseases/diagnosis/*etiology/pathology ; Lung Neoplasms/chemistry/diagnosis/etiology/pathology ; Male ; Mesothelioma/chemistry/diagnosis/etiology/pathology ; Middle Aged ; Mineral Fibers/*analysis ; Occupations ; Pleural Neoplasms/chemistry/diagnosis/etiology/pathology ; Predictive Value of Tests ; ROC Curve ; Retrospective Studies ; Sensitivity and Specificity ; }, abstract = {INTRODUCTION: Bronchoalveolar lavage (BAL) analysis has been proposed as an objective technique for confirming asbestos exposure. However, the reliability and diagnostic yield of this procedure has not been studied in Spain. The aim of this study was to assess the usefulness of the analysis of asbestos bodies (AB) in bronchoalveolar lavage (BAL) for the diagnosis of asbestos-related diseases (ARD).

METHODS: BAL samples from 72 patients (66 male, mean age 66 years) undergoing bronchoscopy were analyzed. Lung tissue from 23 of these patients was also analyzed. Asbestos exposure was assessed by anamnesis and a review of the patient's medical records. BAL and lung samples were processed and AB count was determined by light microscopy. The accepted threshold value to diagnose asbestos-related diseases was 1 AB/ml BAL or 1000 AB/gr dry tissue.

RESULTS: Thirty-nine patients reported exposure to asbestos. Of these, 13 (33%) presented AB values above 1 AB/ml BAL. In the 33 non-exposed patients, 5 (15%) presented AB values above 1 AB/ml BAL. There was a significant difference between the AB levels of exposed and non-exposed patients (P=.006). The ROC curve showed that a value of 0.5 AB/ml BAL achieved the most satisfactory sensitivity, 46%, and a specificity of 83%. The correlation between AB levels in BAL and lung was 0.633 (P=.002).

CONCLUSIONS: BAL study provides objective evidence of exposure to asbestos. The good correlation between the AB counts in BAL and lung tissue indicates that both techniques are valid for the analysis of asbestos content.}, } @article {pmid27908590, year = {2017}, author = {Neyens, T and Lawson, AB and Kirby, RS and Nuyts, V and Watjou, K and Aregay, M and Carroll, R and Nawrot, TS and Faes, C}, title = {Disease mapping of zero-excessive mesothelioma data in Flanders.}, journal = {Annals of epidemiology}, volume = {27}, number = {1}, pages = {59-66.e3}, pmid = {27908590}, issn = {1873-2585}, support = {R01 CA172805/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Age Distribution ; Aged ; Bayes Theorem ; Belgium/epidemiology ; Female ; Geographic Mapping ; Humans ; Incidence ; Lung Neoplasms/diagnosis/*epidemiology/ethnology ; Male ; Mesothelioma/diagnosis/*epidemiology/ethnology ; Mesothelioma, Malignant ; Middle Aged ; Pericardium ; Peritoneal Neoplasms/*epidemiology/ethnology/pathology ; Pleural Neoplasms/*epidemiology/ethnology/pathology ; Poisson Distribution ; *Registries ; Risk Assessment ; Sex Distribution ; Survival Analysis ; }, abstract = {PURPOSE: To investigate the distribution of mesothelioma in Flanders using Bayesian disease mapping models that account for both an excess of zeros and overdispersion.

METHODS: The numbers of newly diagnosed mesothelioma cases within all Flemish municipalities between 1999 and 2008 were obtained from the Belgian Cancer Registry. To deal with overdispersion, zero inflation, and geographical association, the hurdle combined model was proposed, which has three components: a Bernoulli zero-inflation mixture component to account for excess zeros, a gamma random effect to adjust for overdispersion, and a normal conditional autoregressive random effect to attribute spatial association. This model was compared with other existing methods in literature.

RESULTS: The results indicate that hurdle models with a random effects term accounting for extra variance in the Bernoulli zero-inflation component fit the data better than hurdle models that do not take overdispersion in the occurrence of zeros into account. Furthermore, traditional models that do not take into account excessive zeros but contain at least one random effects term that models extra variance in the counts have better fits compared to their hurdle counterparts. In other words, the extra variability, due to an excess of zeros, can be accommodated by spatially structured and/or unstructured random effects in a Poisson model such that the hurdle mixture model is not necessary.

CONCLUSIONS: Models taking into account zero inflation do not always provide better fits to data with excessive zeros than less complex models. In this study, a simple conditional autoregressive model identified a cluster in mesothelioma cases near a former asbestos processing plant (Kapelle-op-den-Bos). This observation is likely linked with historical local asbestos exposures. Future research will clarify this.}, } @article {pmid27907819, year = {2017}, author = {Haji Ali, R and Khalife, M and El Nounou, G and Zuhri Yafi, R and Nassar, H and Aidibe, Z and Raad, R and Abou Eid, R and Faraj, W}, title = {Giant primary malignant mesothelioma of the liver: A case report.}, journal = {International journal of surgery case reports}, volume = {30}, number = {}, pages = {58-61}, pmid = {27907819}, issn = {2210-2612}, abstract = {INTRODUCTION: Malignant mesothelioma is a rare neoplasm of mesothelial cells arising most frequently in the pleura or peritoneum and less frequently in the liver.

CASE PRESENTATION: We present a case of primary hepatic mesothelioma of 41year old woman. She had no history of asbestos exposure or cancer. Abdominal computed tomography (CT) showed 21cm intrahepatic mass in the right lobe with many cystic lesions and few small calcifications. Pathology showed a biphasic cellular pattern. In addition, the tumor cells were positive for Calretinin, Creatine Kinase (CK)5/6, CK7, CKAEI 1/3, Wilms Tumor protein (WT-1), and Vimentin, but were negative for Alpha Feto protein (AFP), Thrombotic Thrombocytopenic Purpura (TTP-1), Anti-Hepatocyte Specific Antigen (HSA), Synaptophysin, CK20, and Homeobox protein (CDx-2).

DISCUSSION: Primary intrahepatic mesothelioma (PIHMM) is not included in the classification of the World Health Organization classification of hepatic tumors. Mesothelial cells are not normally found in the liver, but some reported cases suggest it may grow from the mesothelial cells of the Glisson's capsule.

CONCLUSION: The probability of hepatic mesothelioma should not be ruled out, even in a young woman without a clear history of asbestos exposure.}, } @article {pmid27903668, year = {2016}, author = {Bibby, AC and Tsim, S and Kanellakis, N and Ball, H and Talbot, DC and Blyth, KG and Maskell, NA and Psallidas, I}, title = {Malignant pleural mesothelioma: an update on investigation, diagnosis and treatment.}, journal = {European respiratory review : an official journal of the European Respiratory Society}, volume = {25}, number = {142}, pages = {472-486}, pmid = {27903668}, issn = {1600-0617}, support = {ETM/285/CSO_/Chief Scientist Office/United Kingdom ; }, mesh = {Humans ; Lung Neoplasms/*diagnosis/pathology/*therapy ; Mesothelioma/*diagnosis/pathology/*therapy ; Mesothelioma, Malignant ; Pleural Neoplasms/*diagnosis/pathology/*therapy ; Predictive Value of Tests ; Treatment Outcome ; }, abstract = {Malignant pleural mesothelioma is an aggressive malignancy of the pleural surface, predominantly caused by prior asbestos exposure. There is a global epidemic of malignant pleural mesothelioma underway, and incidence rates are predicted to peak in the next few years.This article summarises the epidemiology and pathogenesis of malignant pleural mesothelioma, before describing some key factors in the patient experience and outlining common symptoms. Diagnostic approaches are reviewed, including imaging techniques and the role of various biomarkers. Treatment options are summarised, including the importance of palliative care and methods of controlling pleural effusions. The evidence for chemotherapy, radiotherapy and surgery is reviewed, both in the palliative setting and in the context of trimodality treatment. An algorithm for managing malignant pleural effusion in malignant pleural mesothelioma patients is presented. Finally new treatment developments and novel therapeutic approaches are summarised.}, } @article {pmid27900083, year = {2016}, author = {Kurosawa, T and Sugino, K and Isobe, K and Hata, Y and Fukasawa, Y and Homma, S}, title = {Primary malignant pericardial mesothelioma with increased serum mesothelin diagnosed by surgical pericardial resection: A case report.}, journal = {Molecular and clinical oncology}, volume = {5}, number = {5}, pages = {553-556}, pmid = {27900083}, issn = {2049-9450}, abstract = {A 37-year-old female smoker without a history of exposure to asbestos was referred to our hospital with persistent pericardial effusion. Chest computed tomography imaging examination revealed an irregular thickened pericardium with large amounts of pericardial effusion and a small pleural effusion. Fluorodeoxyglucose (FDG) positron emission tomography imaging demonstrated intrapericardial FDG accumulation. Blood tests revealed an increase in serum mesothelin levels. Examination of a surgically resected specimen revealed a grayish-white thickening of the pericardium, with a straw-colored mucinous pericardial effusion. Histopathological examination confirmed the diagnosis of epithelioid malignant mesothelioma. Although the patient's condition temporarily improved, with decreased levels of serum mesothelin during chemotherapy with carboplatin and pemetrexed, she succumbed to cardiac tamponade 18 months after the initial onset of the symptoms. Primary malignant pericardial mesothelioma (PMPM) is an extremely rare and refractory disorder. Thus, an early definitive diagnosis and timely treatment are crucial for the management of PMPM.}, } @article {pmid27900005, year = {2016}, author = {Rapisarda, V and Salemi, R and Marconi, A and Loreto, C and Graziano, AC and Cardile, V and Basile, MS and Candido, S and Falzone, L and Spandidos, DA and Fenga, C and Libra, M}, title = {Fluoro-edenite induces fibulin-3 overexpression in non-malignant human mesothelial cells.}, journal = {Oncology letters}, volume = {12}, number = {5}, pages = {3363-3367}, pmid = {27900005}, issn = {1792-1074}, abstract = {Exposure to asbestos is associated with the development of mesothelioma. In addition to asbestos, other fibers have been identified as risk factors for malignant and non-malignant diseases of the lungs. Among these, fluoro-edenite (FE) was found in patients from Biancavilla (Sicily, Italy) with pleural and lung disease, suggesting its role for tumor expansion. In this context, the identification of early biomarkers useful for the diagnosis of cancer is mandatory. Fibulin-3 represents an important marker for the diagnosis of mesothelioma. However, it remains to be determined whether it is directly associated with exposure to asbestos-like fibers. In the present study, peripheral blood levels of fibulin-3 from 40 asbestos-exposed workers were compared with those detected in 27 street cleaners from Biancavilla. Intriguingly, the results showed that fibulin-3 levels were higher in the group of street cleaners compared with those of the asbestos-exposed workers, suggesting that these workers used the personal protective equipment according to the current regulations. These data suggest that subjects exposed to FE should be monitored for the risk of mesothelioma. FE and volcanic particulates are probably contained within dust inhaled by street cleaners from Biancavilla during their work activities. Based on these criteria, in this study, such fibers were used to treat mesothelial cells (MeT5A) in order to verify whether fibulin-3 levels are affected by these treatments. The results showed that only treatment with FE was associated with fibulin-3 overexpression at both the transcript and protein levels. It was previously demonstrated that mesothelial cells exhibited low levels of p27 following treatment with FE. Notably, p27 downregulation is associated with stathmin upregulation in cancer, conferring an aggressive phenotype of tumor cells. This observation prompted us to perform a computational evaluation demonstrating the activation of stathmin in lung cancer in patients exposed to asbestos. Overall, it can be speculated that both fibulin-3 and stathmin overexpression may be associated with the malignant transformation of mesothelial cells following exposure to asbestos-like fibers.}, } @article {pmid27889700, year = {2017}, author = {Reinstein, L and Bersin, B}, title = {Clarence Borel.}, journal = {New solutions : a journal of environmental and occupational health policy : NS}, volume = {26}, number = {4}, pages = {622-629}, doi = {10.1177/1048291116679964}, pmid = {27889700}, issn = {1541-3772}, mesh = {*Asbestos ; Asbestosis/*history ; History, 20th Century ; Humans ; Jurisprudence/*history ; Lung Neoplasms ; Male ; Mesothelioma ; Middle Aged ; United States ; }, abstract = {Borel v. Fibreboard Paper Products Corporation is the 1973 landmark case that paved the way for successful litigation against the asbestos industry. Clarence Borel's granddaughter shares recollections of the reluctant man behind the court case.}, } @article {pmid27886205, year = {2016}, author = {Lansley, SM and Pedersen, B and Robinson, C and Searles, RG and Sterrett, G and van Bruggen, I and Lake, RA and Mutsaers, SE and Prêle, CM}, title = {A Subset of Malignant Mesothelioma Tumors Retain Osteogenic Potential.}, journal = {Scientific reports}, volume = {6}, number = {}, pages = {36349}, pmid = {27886205}, issn = {2045-2322}, mesh = {Adult ; Alkaline Phosphatase/metabolism ; Animals ; Biomarkers/*metabolism ; Cell Differentiation ; Cell Line, Tumor ; Core Binding Factor Alpha 1 Subunit/metabolism ; Dexamethasone/pharmacology/therapeutic use ; Female ; Humans ; Integrin-Binding Sialoprotein/genetics/metabolism ; Lung Neoplasms/drug therapy/genetics/*metabolism ; Mesothelioma/drug therapy/genetics/*metabolism ; Mesothelioma, Malignant ; Mice ; Neoplasm Transplantation ; Osteoblasts/*cytology/metabolism ; *Osteogenesis/drug effects ; Osteonectin/metabolism ; }, abstract = {Malignant mesothelioma (MM) is an aggressive serosal tumor associated with asbestos exposure. We previously demonstrated that mesothelial cells differentiate into cells of different mesenchymal lineages and hypothesize that osseous tissue observed in a subset of MM patients is due to local differentiation of MM cells. In this study, the capacity of human and mouse MM cells to differentiate into osteoblast-like cells was determined in vitro using a functional model of bone nodule formation and in vivo using an established model of MM. Human and murine MM cell lines cultured in osteogenic medium expressed alkaline phosphatase and formed mineralized bone-like nodules. Several human and mouse MM cell lines also expressed a number of osteoblast phenotype markers, including runt-related transcription factor 2 (RUNX2), osteopontin, osteonectin and bone sialoprotein mRNA and protein. Histological analysis of murine MM tumors identified areas of ossification within the tumor, similar to those observed in human MM biopsies. These data demonstrate the ability of MM to differentiate into another mesenchymal cell type and suggest that MM cells may contribute to the formation of the heterologous elements observed in MM tumors.}, } @article {pmid27884852, year = {2016}, author = {Tsim, S and Kelly, C and Alexander, L and McCormick, C and Thomson, F and Woodward, R and Foster, JE and Stobo, DB and Paul, J and Maskell, NA and Chalmers, A and Blyth, KG}, title = {Diagnostic and Prognostic Biomarkers in the Rational Assessment of Mesothelioma (DIAPHRAGM) study: protocol of a prospective, multicentre, observational study.}, journal = {BMJ open}, volume = {6}, number = {11}, pages = {e013324}, pmid = {27884852}, issn = {2044-6055}, support = {15960/CRUK_/Cancer Research UK/United Kingdom ; ETM/285/CSO_/Chief Scientist Office/United Kingdom ; }, mesh = {Biomarkers, Tumor/blood ; Cross-Sectional Studies ; Extracellular Matrix Proteins/*blood ; GPI-Linked Proteins/*blood ; Humans ; Lung Neoplasms/*blood/*diagnostic imaging ; Magnetic Resonance Imaging ; Mesothelin ; Mesothelioma/*blood/*diagnostic imaging ; Mesothelioma, Malignant ; Prognosis ; Prospective Studies ; Proteomics/methods ; ROC Curve ; Research Design ; Scotland ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is an asbestos-related cancer, which is difficult to diagnose. Thoracoscopy is frequently required but is not widely available. An accurate, non-invasive diagnostic biomarker would allow early specialist referral, limit diagnostic delays and maximise clinical trial access. Current markers offer insufficient sensitivity and are not routinely used. The SOMAmer proteomic classifier and fibulin-3 have recently demonstrated sensitivity and specificity exceeding 90% in retrospective studies. DIAPHRAGM (Diagnostic and Prognostic Biomarkers in the Rational Assessment of Mesothelioma) is a suitably powered, multicentre, prospective observational study designed to determine whether these markers provide clinically useful diagnostic and prognostic information.

METHODS AND ANALYSIS: Serum and plasma (for SOMAscan and fibulin-3, respectively) will be collected at presentation, prior to pleural biopsy/pleurodesis, from 83 to 120 patients with MPM, at least 480 patients with non-MPM pleural disease and 109 asbestos-exposed controls. Final numbers of MPM/non-MPM cases will depend on the incidence of MPM in the study population (estimated at 13-20%). Identical sampling and storage protocols will be used in 22 recruiting centres and histological confirmation sought in all cases. Markers will be measured using the SOMAscan proteomic assay (SomaLogic) and a commercially available fibulin-3 ELISA (USCN Life Science). The SE in the estimated sensitivity and specificity will be <5% for each marker and their performance will be compared with serum mesothelin. Blood levels will be compared with paired pleural fluid levels and MPM tumour volume (using MRI) in a nested substudy. The prognostic value of each marker will be assessed and a large bioresource created.

ETHICS AND DISSEMINATION: The study has been approved by the West of Scotland Research Ethics Committee (Ref: 13/WS/0240). A Trial Management Group meets on a monthly basis. Results will be published in peer-reviewed journals, presented at international meetings and disseminated to patient groups.

TRIAL REGISTRATION NUMBER: ISRCTN10079972, Pre-results.}, } @article {pmid27878235, year = {2017}, author = {Lee, S and Matsuzaki, H and Maeda, M and Yamamoto, S and Kumagai-Takei, N and Hatayama, T and Ikeda, M and Yoshitome, K and Nishimura, Y and Otsuki, T}, title = {Accelerated cell cycle progression of human regulatory T cell-like cell line caused by continuous exposure to asbestos fibers.}, journal = {International journal of oncology}, volume = {50}, number = {1}, pages = {66-74}, pmid = {27878235}, issn = {1791-2423}, mesh = {CD4-Positive T-Lymphocytes/immunology/pathology ; Cell Cycle/drug effects/immunology ; Cyclin D1/biosynthesis/blood/*immunology ; Forkhead Box Protein O1/*biosynthesis/immunology ; Gene Expression Regulation, Neoplastic ; Humans ; Interleukin-10/biosynthesis/blood/immunology ; Killer Cells, Natural/immunology ; Lung Neoplasms/blood/chemically induced/*immunology/pathology ; Mesothelioma/blood/chemically induced/*immunology/pathology ; Mesothelioma, Malignant ; Natural Cytotoxicity Triggering Receptor 1/biosynthesis/blood/immunology ; Receptors, CXCR3/biosynthesis/immunology ; T-Lymphocytes, Cytotoxic/drug effects/immunology ; T-Lymphocytes, Regulatory/drug effects/*immunology ; Transforming Growth Factor beta/biosynthesis/blood/immunology ; }, abstract = {Asbestos exposure causes malignant tumors such as lung cancer and malignant mesothelioma. Based on our hypothesis in which continuous exposure to asbestos of immune cells cause reduction of antitumor immunity, the decrease of natural killer cell killing activity with reduction of NKp46 activating receptor expression, inhibition of cytotoxic T cell clonal expansion, reduced CXCR3 chemokine receptor expression and production of interferon-γ production in CD4+ T cells were reported using cell line models, freshly isolated peripheral blood immune cells from health donors as well as asbestos exposed patients such as pleural plaque and mesothelioma. In addition to these findings, regulatory T cells (Treg) showed enhanced function through cell-cell contact and increased secretion of typical soluble factors, interleukin (IL)-10 and transforming growth factor (TGF)-β, in a cell line model using the MT-2 human polyclonal T cells and its sublines exposed continuously to asbestos fibers. Since these sublines showed a remarkable reduction of FoxO1 transcription factor, which regulates various cell cycle regulators in asbestos-exposed sublines, the cell cycle progression in these sublines was examined and compared with that of the original MT-2 cells. Results showed that cyclin D1 expression was markedly enhanced, and various cyclin-dependent kinase-inhibitors were reduced with increased S phases in the sublines. Furthermore, the increase of cyclin D1 expression was regulated by FoxO1. The overall findings indicate that antitumor immunity in asbestos-exposed individuals may be reduced in Treg through changes in the function and volume of Treg.}, } @article {pmid27872401, year = {2017}, author = {Castleman, B}, title = {Criminality and Asbestos in Industry.}, journal = {New solutions : a journal of environmental and occupational health policy : NS}, volume = {26}, number = {4}, pages = {557-580}, doi = {10.1177/1048291116678435}, pmid = {27872401}, issn = {1541-3772}, mesh = {*Asbestos ; *Crime ; Disasters ; Humans ; Industry/*legislation & jurisprudence ; Italy ; Mesothelioma ; *Occupational Exposure ; }, abstract = {Criminal prosecutions of individuals in the asbestos industry are reviewed, particularly the case of asbestos owner-executive Stephan Schmidheiny. Italian courts sentenced Schmidheiny to sixteen to eighteen years in jail for creating an environmental disaster causing three thousand deaths. The convictions were overturned on a technicality, and a murder case against Schmidheiny has started. His firm, Eternit, made asbestos-cement building products in many countries. Schmidheiny directed a cover-up that the Italian Court of Appeal blamed for delaying the ban of asbestos in Italy by ten years. Today, the asbestos industry is a criminal industry, profiting only by minimizing its costs for the prevention and compensation of occupational and environmental illness. The asbestos industry should only be consulted by governments for the purpose of closing it and dealing with the legacy of in-place asbestos.}, } @article {pmid27870118, year = {2016}, author = {Boffetta, P}, title = {Re: Terracini et al. Comments on the causation of malignant mesothelioma: Rebutting the false concept that recent exposures to asbestos do not contribute to causation of mesothelioma. Am J Ind Med 2016;59:506-507.}, journal = {American journal of industrial medicine}, volume = {59}, number = {12}, pages = {1177-1179}, doi = {10.1002/ajim.22672}, pmid = {27870118}, issn = {1097-0274}, mesh = {Asbestos ; Humans ; *Lung Neoplasms ; *Mesothelioma ; }, } @article {pmid27869238, year = {2016}, author = {Smolková, P and Nakládalová, M and Zapletalová, J}, title = {Response to the letter to editors concerning "Validity of mesothelin in occupational medicine practice".}, journal = {International journal of occupational medicine and environmental health}, volume = {29}, number = {6}, pages = {881}, doi = {10.13075/ijomeh.1896.01101}, pmid = {27869238}, issn = {1896-494X}, mesh = {Asbestos ; *GPI-Linked Proteins ; Humans ; Mesothelin ; Mesothelioma ; Occupational Exposure ; *Occupational Medicine ; Pleural Neoplasms ; }, } @article {pmid27869237, year = {2016}, author = {Taeger, D and Gawrych, K and Brüning, T}, title = {Validity of mesothelin in occupational medicine practice.}, journal = {International journal of occupational medicine and environmental health}, volume = {29}, number = {6}, pages = {879-880}, doi = {10.13075/ijomeh.1896.01062}, pmid = {27869237}, issn = {1896-494X}, mesh = {Asbestos ; *GPI-Linked Proteins ; Humans ; Mesothelin ; Mesothelioma ; Occupational Exposure ; *Occupational Medicine ; Pleural Neoplasms ; }, } @article {pmid27866405, year = {2016}, author = {Plato, N and Martinsen, JI and Sparén, P and Hillerdal, G and Weiderpass, E}, title = {Occupation and mesothelioma in Sweden: updated incidence in men and women in the 27 years after the asbestos ban.}, journal = {Epidemiology and health}, volume = {38}, number = {}, pages = {e2016039}, pmid = {27866405}, issn = {2092-7193}, mesh = {Adult ; Asbestos/poisoning ; Asbestosis/epidemiology ; Female ; Humans ; Incidence ; Male ; Mesothelioma/chemically induced/*epidemiology ; Middle Aged ; Occupational Diseases/chemically induced/*epidemiology ; Registries ; Sweden/epidemiology ; }, abstract = {OBJECTIVES: We updated the Swedish component of the Nordic Occupational Cancer (NOCCA) Study through 2009 in order to investigate the incidence of mesothelioma of the peritoneum and pleura in both genders, and explored occupational exposures that may be associated with mesothelioma.

METHODS: The Swedish component of the NOCCA Study includes 6.78 million individuals. Data from this cohort were linked to the population-based Swedish Cancer Registry and Swedish Total Population Registry for three periods between 1961 and 2009, and then further linked to the Swedish NOCCA job-exposure matrix, which includes 25 carcinogenic substances and the corresponding exposure levels for 280 occupations. Multivariate analysis was used to calculate standardized incidence ratios (SIRs) for mesothelioma of the peritoneum and pleura by gender, occupational category, carcinogenic substance, and for multiple occupational exposures simultaneously.

RESULTS: A total of 3,716 incident mesotheliomas were recorded (21.1% in women). We found a significantly increased risk of mesothelioma in 24 occupations, as well as clear differences between the genders. Among men, increased risks of mesothelioma of the pleura were observed in male-dominated occupations, with the greatest elevation of risk among plumbers (SIR, 4.99; 95% confidence interval, 4.20 to 5.90). Among women, increased risks were observed in sewing workers, canning workers, packers, cleaners, and postal workers. In multivariate analysis controlling for multiple occupational exposures, significant associations were only observed between asbestos exposure and mesothelioma.

CONCLUSIONS: Asbestos exposure was associated with mesothelioma incidence in our study. The asbestos ban of 1982 has yet to show any clear effect on the occurrence of mesothelioma in this cohort. Among women, the occupations of canning workers and cleaners showed increased risks of mesothelioma of the pleura without evidence of asbestos exposure.}, } @article {pmid27859460, year = {2017}, author = {Shinozaki-Ushiku, A and Ushiku, T and Morita, S and Anraku, M and Nakajima, J and Fukayama, M}, title = {Diagnostic utility of BAP1 and EZH2 expression in malignant mesothelioma.}, journal = {Histopathology}, volume = {70}, number = {5}, pages = {722-733}, doi = {10.1111/his.13123}, pmid = {27859460}, issn = {1365-2559}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Enhancer of Zeste Homolog 2 Protein/analysis/*biosynthesis ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lung Neoplasms/*diagnosis/mortality/pathology ; Male ; Mesothelioma/*diagnosis/mortality/pathology ; Mesothelioma, Malignant ; Middle Aged ; Proportional Hazards Models ; Tumor Suppressor Proteins/analysis/*biosynthesis ; Ubiquitin Thiolesterase/analysis/*biosynthesis ; }, abstract = {AIMS: Malignant mesothelioma is a highly aggressive cancer that is usually diagnosed at advanced stages; thus, highly sensitive and specific markers are necessary for its early definitive diagnosis. The aim of this study was to evaluate the diagnostic utility and prognostic significance of BAP1 and EZH2 in malignant mesothelioma.

METHODS AND RESULTS: The expression of BAP1 and EZH2 was investigated by immunohistochemistry in 32 malignant mesotheliomas and 44 benign mesothelial proliferative lesions, including well-differentiated papillary mesothelioma (n = 4), mesothelial inclusion cyst (n = 22), and reactive mesothelial hyperplasia (n = 18). BAP1 loss and high EZH2 expression were observed in 17 (53%) and 22 (66%) malignant mesothelioma cases, respectively, whereas none of the benign lesions showed BAP1 loss or high EZH2 expression. The combination of BAP1 loss and high EZH2 expression as markers to differentiate epithelioid/biphasic malignant mesothelioma from benign mesothelial lesions was highly sensitive (90%) and specific (100%). There were no statistically significant associations between parameters such as age and sex of patients, tumour location, asbestos exposure, treatment, histology, and BAP1 or EZH2 expression. Survival analysis revealed that BAP1 loss, but not high EZH2 expression, was associated with a better prognosis.

CONCLUSIONS: BAP1 loss and high EZH2 expression were highly specific to malignant mesothelioma in differentiating it from benign mesothelial proliferations, and the combination of these two markers improved the diagnostic accuracy.}, } @article {pmid27840913, year = {2016}, author = {Kato, T and Lee, D and Wu, L and Patel, P and Young, AJ and Wada, H and Hu, HP and Ujiie, H and Kaji, M and Kano, S and Matsuge, S and Domen, H and Kanno, H and Hatanaka, Y and Hatanaka, KC and Kaga, K and Matsui, Y and Matsuno, Y and De Perrot, M and Yasufuku, K}, title = {SORORIN and PLK1 as potential therapeutic targets in malignant pleural mesothelioma.}, journal = {International journal of oncology}, volume = {49}, number = {6}, pages = {2411-2420}, doi = {10.3892/ijo.2016.3765}, pmid = {27840913}, issn = {1791-2423}, mesh = {Adaptor Proteins, Signal Transducing/*antagonists & inhibitors/biosynthesis/genetics ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics ; Cell Cycle Proteins/*antagonists & inhibitors/biosynthesis/genetics ; Cell Line, Tumor ; Cell Proliferation/drug effects/genetics ; Female ; G2 Phase Cell Cycle Checkpoints/genetics ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/*pathology ; Male ; Mesothelioma/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/*pathology ; Protein Serine-Threonine Kinases/*antagonists & inhibitors/genetics ; Proto-Oncogene Proteins/*antagonists & inhibitors/genetics ; Pteridines/pharmacology ; RNA Interference ; RNA, Small Interfering/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Polo-Like Kinase 1 ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive type of cancer of the thoracic cavity commonly associated with asbestos exposure and a high mortality rate. There is a need for new molecular targets for the development of more effective therapies for MPM. Using quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and an RNA interference-based screening, we examined the SORORIN gene as potential therapeutic targets for MPM in addition to the PLK1 gene, which is known for kinase of SORORIN. Following in vitro investigation of the effects of target silencing on MPM cells, cell cycle analyses were performed. SORORIN expression was analyzed immunohistochemically using a total of 53 MPM samples on tissue microarray. SORORIN was found to be overexpressed in the majority of clinical MPM samples and human MPM cell lines as determined by qRT-PCR. Gene suppression of each SORORIN and PLK1 led to growth inhibition in MPM cell lines. Knockdown of SORORIN showed an increased number of G2M-phase population and a larger nuclear size, suggesting mitotic arrest. High expression of SORORIN (SORORIN-H) was found in 50.9% of all the MPM cases, and there is a tendency towards poorer prognosis for the SORORIN-H group but the difference is not significant. Suppression of SORORIN with PLK1 inhibitor BI 6727 showed a combinational growth suppressive effect on MPM cell growth. Given high-dose PLK1 inhibitor induced drug-related adverse effects in several clinical trials, our results suggest inhibition SORORIN-PLK1 axis may hold promise for the treatment of MPMs.}, } @article {pmid27835874, year = {2017}, author = {Bruno, R and Alì, G and Giannini, R and Proietti, A and Lucchi, M and Chella, A and Melfi, F and Mussi, A and Fontanini, G}, title = {Malignant pleural mesothelioma and mesothelial hyperplasia: A new molecular tool for the differential diagnosis.}, journal = {Oncotarget}, volume = {8}, number = {2}, pages = {2758-2770}, pmid = {27835874}, issn = {1949-2553}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; Cluster Analysis ; Computational Biology/methods ; Diagnosis, Differential ; Female ; Gene Expression Profiling/methods ; Gene Expression Regulation, Neoplastic ; Humans ; Hyperplasia ; Lung Neoplasms/*diagnosis/*genetics ; Male ; Mesothelioma/*diagnosis/*genetics ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/*diagnosis/*genetics ; Young Adult ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare asbestos related cancer, aggressive and unresponsive to therapies. Histological examination of pleural lesions is the gold standard of MPM diagnosis, although it is sometimes hard to discriminate the epithelioid type of MPM from benign mesothelial hyperplasia (MH).This work aims to define a new molecular tool for the differential diagnosis of MPM, using the expression profile of 117 genes deregulated in this tumour.The gene expression analysis was performed by nanoString System on tumour tissues from 36 epithelioid MPM and 17 MH patients, and on 14 mesothelial pleural samples analysed in a blind way. Data analysis included raw nanoString data normalization, unsupervised cluster analysis by Pearson correlation, non-parametric Mann Whitney U-test and molecular classification by the Uncorrelated Shrunken Centroid (USC) Algorithm.The Mann-Whitney U-test found 35 genes upregulated and 31 downregulated in MPM. The unsupervised cluster analysis revealed two clusters, one composed only of MPM and one only of MH samples, thus revealing class-specific gene profiles. The Uncorrelated Shrunken Centroid algorithm identified two classifiers, one including 22 genes and the other 40 genes, able to properly classify all the samples as benign or malignant using gene expression data; both classifiers were also able to correctly determine, in a blind analysis, the diagnostic categories of all the 14 unknown samples.In conclusion we delineated a diagnostic tool combining molecular data (gene expression) and computational analysis (USC algorithm), which can be applied in the clinical practice for the differential diagnosis of MPM.}, } @article {pmid27829301, year = {2016}, author = {Dodge, DG and Beck, BD}, title = {Historical state of knowledge of the health risks of asbestos posed to seamen on merchant ships.}, journal = {Inhalation toxicology}, volume = {28}, number = {14}, pages = {637-657}, doi = {10.1080/08958378.2016.1244228}, pmid = {27829301}, issn = {1091-7691}, mesh = {Air Pollutants, Occupational/analysis/*history/*toxicity ; Animals ; Asbestos/analysis/*history/*toxicity ; History, 20th Century ; History, 21st Century ; Humans ; Naval Medicine/history ; Occupational Diseases/etiology/history/prevention & control ; Occupational Exposure/adverse effects/analysis/history/prevention & control ; Occupational Health ; Risk ; *Ships ; }, abstract = {We examined the development of knowledge concerning the risks posed by asbestos to seamen working aboard merchant ships at sea (i.e. commercial, rather than naval vessels). Seamen were potentially exposed to "in-place" asbestos on merchant ships by performing intermittent repair and maintenance tasks. We reviewed studies measuring airborne asbestos onboard merchant ships and health outcomes of merchant seamen, as well as studies, communications, and actions of U.S. organizations with roles in maritime health and safety. Up to the 1970s, most knowledge of the health risks of asbestos was derived from studies of workers in asbestos product manufacturing and asbestos mining and milling industries, and certain end-users of asbestos products (particularly insulators). We found that attention to the potential health risks of asbestos to merchant seamen began in the mid- to late 1970s and early 1980s. Findings of pleural abnormalities in U.S. seamen elicited some concern from governmental and industry/labor organizations, but airborne asbestos concentrations aboard merchant ships were found to be <1 f/cc for most short-term repair and maintenance tasks. Responses to this evolving information served to warn seamen and the merchant shipping industry and led to increased precautions regarding asbestos exposure. Starting in the 1990s, findings of modest increases in lung cancer and/or mesothelioma in some epidemiology studies of seamen led some authors to propose that a causal link between shipboard exposures and asbestos-related diseases existed. Limitations in these studies, however, together with mostly unremarkable measures of airborne asbestos on merchant ships, preclude definitive conclusions in this regard.}, } @article {pmid27825201, year = {2016}, author = {Conti, S and Comba, P and Manno, V and Minelli, G and Nicita, C and Pasetto, R and Fazzo, L and Zona, A and Bruno, C}, title = {[SENTIERI-ReNaM: Integration of incidence, mortality, and hospitalization: general remarks and a focus on mesothelioma].}, journal = {Epidemiologia e prevenzione}, volume = {40}, number = {5Suppl1}, pages = {109-115}, pmid = {27825201}, issn = {1120-9763}, mesh = {Asbestos/toxicity ; Carcinogens, Environmental/toxicity ; Confidence Intervals ; *Environmental Exposure ; *Environmental Pollution ; Female ; *Hazardous Waste Sites ; Health Surveys ; Humans ; Incidence ; Industry ; Italy ; Male ; Mesothelioma/*epidemiology/etiology ; Occupational Exposure ; Registries ; Risk ; }, abstract = {The integration of current data sources is now a practice widely used in epidemiology, especially in the environmental field. To better describe the health profile of populations residing in proximity to areas characterized by a "strong environmental pressure", the combined use of multiple indicators (i.e., mortality, hospitalization, cancer incidence) is recommended. To choose an indicator is complex, as indicators should be contextualized and they need to be related to the several issues involved in the studied pathology. This chapter explores the general considerations that are to be addressed both at the time of the study design, during the selection of outcomes and of the proper data sources, and at the time of the discussion of the results, when different and complementary data are compared. A special focus is devoted to the case of mesothelioma.}, } @article {pmid27825200, year = {2016}, author = {Zona, A and Fazzo, L and Binazzi, A and Bruno, C and Corfiati, M and Comba, P and Conti, S and Menegozzo, S and Nicita, C and Pasetto, R and Pirastu, R and Marinaccio, A and , }, title = {[SENTIERI-ReNaM: Discussion and concluding remarks].}, journal = {Epidemiologia e prevenzione}, volume = {40}, number = {5Suppl1}, pages = {105-108}, pmid = {27825200}, issn = {1120-9763}, mesh = {Asbestos/toxicity ; Carcinogens, Environmental/toxicity ; Confidence Intervals ; *Environmental Exposure ; *Environmental Pollution ; Female ; *Hazardous Waste Sites ; Health Surveys ; Humans ; Incidence ; Industry ; Italy ; Male ; Mesothelioma/*epidemiology/etiology ; Occupational Exposure ; Registries ; Risk ; }, abstract = {SENTIERI-ReNaM Project analysed the incidence of malignant mesothelioma (MM) for the period 2000-2011 in 39 National Priority Contaminated Sites (NPCSs), and assessed the overall impact of mesothelioma in different types of NPCSs. In the study period, 2,683 incident cases of malignant mesothelioma were recorded: 1,998 males (74.5%), 685 females (25.5%). Excluding cases with non attributable exposure and those non interviewed, exposure was identified in 1,926 cases (70% of all cases): 1,541 males (occupational exposure: 1,414; environmental exposure: 82), 385 females (occupational exposure: 103; environmental exposure: 141). Women experienced mainly environmental and domestic exposures to asbestos. Standard Incidence Ratio (SIR) excesses were observed in men in 27 out of 39 NPCSs and defects in the remaining 12; in women, 20 NPCSs showed SIR excesses, defects in 15; in 4 NPCSs no MM cases occurred among female population. The highest rates were found in NPCSs with asbestos-cement plants (Broni and Casale Monferrato), respectively, 98 per 100,000 per year and 68.6 in men, 72.1 and 45.8 in women. Excluding these two sites, the highest incidence rates were found in the group with harbours and shipyards, where the rates were, respectively, 13.2 among men and 2.5 among women. The results of this report will be communicated to national and local institutions, as well as to NPCSs resident populations.}, } @article {pmid27825199, year = {2016}, author = {Pasetto, R and Fazzo, L and Zona, A and Bruno, C and Pirastu, R and Binazzi, A and Corfiati, M and Silvestri, S and Comba, P and Marinaccio, A}, title = {[SENTIERI-ReNaM: Burden of disease from mesothelioma in national priority contaminated sites in Italy].}, journal = {Epidemiologia e prevenzione}, volume = {40}, number = {5Suppl1}, pages = {99-104}, pmid = {27825199}, issn = {1120-9763}, mesh = {Asbestos/toxicity ; Carcinogens, Environmental/toxicity ; Confidence Intervals ; *Environmental Exposure ; *Environmental Pollution ; Female ; *Hazardous Waste Sites ; Health Surveys ; Humans ; Incidence ; Industry ; Italy ; Male ; Mesothelioma/*epidemiology/etiology ; Occupational Exposure ; Registries ; Risk ; }, abstract = {BACKGROUND: in Italy, National Priority Contaminated Sites (NPCSs) are defined as of concern for remediation; most of them are sites with a long-lasting industrial activity.

OBJECTIVE: the study aims to estimate the burden of disease from mesothelioma in NPCSs.

DESIGN: mesothelioma incidence in the period 2000-2011 was estimated for the populations residing in the 39 Italian NPCSs. Data were taken from the Italian National Mesothelioma Registry (ReNaM). NPCSs were ranked into risk groups (RGs) on the basis of the presence of the following asbestos-exposing activities: 1. asbestos-cement plants; 2. asbestos mines; 3. harbours with shipyards; 4. illegal dumping sites containing asbestos; 5. petrochemicals and/or refineries, and/or steel plants; 6. chemical plants and/or landfills without explicit mention of asbestos. For the population residing in each NPCS, crude rates per 100,000 per year and number of observed minus expected cases (Obs-Exp) by gender were computed. Expected cases were calculated using the age-class rates of a reference population (the geographical macroarea of every NPCS). For every RG, the meta-analytic estimate of the attributable proportion (AP), i.e., the proportion of cases attributable to the local context, was computed, being the AP for each NPCS expressed as (Obs-Exp/Obs) x100.

RESULTS: the total number of mesothelioma cases estimated in the considered period of 12 years is 2,741 (2,048 males, 693 females). The total number of Obs-Exp cases was 1,531 (1,178 in males, 353 in females). In males, crude rate ranges from 71.5 in the RG1 to 3.0 in RG4, while in females it ranges from 48.4 in RG1 to 0.6 in RG4. In males, AP in RGs from 1 to 3 is over 65%, in RG4 is 59%, in RG5 is 30%, in RG6 is -14%. AP in females gradually drops from 95% in RG1 to -64% in RG6.

CONCLUSIONS: the burden of mesothelioma in populations residing in NPCSs is high, with an AP gradient consistent with the a priori RG. This burden impacts on females in a different way: rates are lower than male ones; AP is similar to male ones in the RGs 1 and 3.}, } @article {pmid27825198, year = {2016}, author = {Binazzi, A and Zona, A and Marinaccio, A and Bruno, C and Corfiati, M and Fazzo, L and Menegozzo, S and Nicita, C and Pasetto, R and Pirastu, R and De Santisi, M and Comba, P and , }, title = {[SENTIERI-ReNaM: Results].}, journal = {Epidemiologia e prevenzione}, volume = {40}, number = {5Suppl1}, pages = {19-98}, pmid = {27825198}, issn = {1120-9763}, mesh = {Asbestos/toxicity ; Carcinogens, Environmental/toxicity ; Confidence Intervals ; *Environmental Exposure ; *Environmental Pollution ; Female ; *Hazardous Waste Sites ; Health Surveys ; Humans ; Incidence ; Industry ; Italy ; Male ; Mesothelioma/*epidemiology/etiology ; Occupational Exposure ; Registries ; Risk ; }, abstract = {Mesothelioma incidence has been analyzed in National Priority Contaminated Sites (NPCSs) to estimate the health impact of asbestos exposure on resident people. The burden of professional and environmental exposures has been identified through data of the Regional Operational Centres (CORs), made available by the Italian National Mesothelioma Registry (ReNaM). An excess of mesothelioma incidence is confirmed in sites with a known past history of direct use of asbestos, such as Balangero, Casale Monferrato, Broni, Bari-Fibronit, and in coastal areas, where shipyards, harbours and other industries that involved a wide use of asbestos are represented (e.g., Trieste, La Spezia, Venice, and Leghorn). An excess of mesothelioma has been observed in settings where the asbestos is not mentioned as contaminant in the decree that included these sites among NPCSs, such as Cengio and Saliceto in Northern Italy; Falconara Marittima and the Bacino Idrografico Fiume Sacco in the Central Italy; the Litorale Domizio Flegreo and Agro Aversano, Milazzo, and Gela in the Southern Italy. Observed excess in the various NPCSs confirms the large-scale occurrence in contaminated Italian sites of a significant amount of total mesothelioma cases observed at national level. The analysis of occupational risk in epidemiological studies with an ecological design helps in defining the contribution of different factors to the overall risk.}, } @article {pmid27825197, year = {2016}, author = {Marinaccio, A and Binazzi, A and Comba, P and Corfiati, M and Fazzo, L and Bruno, C and Pirastu, R and Pasetto, R and Zona, A}, title = {[SENTIERI-ReNaM: Materials and methods].}, journal = {Epidemiologia e prevenzione}, volume = {40}, number = {5Suppl1}, pages = {16-18}, pmid = {27825197}, issn = {1120-9763}, mesh = {Asbestos/toxicity ; Carcinogens, Environmental/toxicity ; Confidence Intervals ; *Environmental Exposure ; *Environmental Pollution ; Female ; *Hazardous Waste Sites ; Health Surveys ; Humans ; Incidence ; Industry ; Italy ; Male ; Mesothelioma/*epidemiology/etiology ; Occupational Exposure ; Registries ; Risk ; }, abstract = {In the framework of SENTIERI Project, this study is aimed to identify excess risks of malignant mesothelioma (MM) in Italian National Priority Contaminated Sites (NPCSs) included in the national environmental remediation programme and to discuss the results by means of data available from the Italian National Mesothelioma Registry (ReNaM). Re- NaM has a regional structure with Regional Operational Centres (CORs) in charge of identifying mesothelioma incident cases and defining the asbestos exposure modalities thought an individual questionnaire. Starting from the 44 NPCSs selected in SENTIERI Project, we excluded Calabria and Sardinia Regions from the analyses (3 NPCSs). Furthermore, for 2 sites (Emarese in Valle d'Aosta and Tito in Basilicata) no incident MM cases have been detected in the considered period. Incident cases of MM and Standardized Incidence Ratios (SIR), with corresponding 90% confidence intervals, have been estimated in each NPCS, for both gender, in the period 2000-2011. Age-standardized rates of Italian geographical macro-areas (North- East, North-West, Centre, South and Islands) have been used to estimate expected cases. For every analyzed site, the occupational and non-occupational asbestos exposure modalities are discussed.}, } @article {pmid27825196, year = {2016}, author = {Comba, P and Zona, A and Pirastu, R and Bruno, C and Fazzo, L and Pasetto, R and Binazzi, A and Corfiati, M and Marinaccio, A}, title = {[SENTIERI-ReNaM: Rationale and objectives].}, journal = {Epidemiologia e prevenzione}, volume = {40}, number = {5Suppl1}, pages = {13-15}, pmid = {27825196}, issn = {1120-9763}, mesh = {Asbestos/toxicity ; Carcinogens, Environmental/toxicity ; Confidence Intervals ; *Environmental Exposure ; *Environmental Pollution ; Female ; *Hazardous Waste Sites ; Health Surveys ; Humans ; Incidence ; Industry ; Italy ; Male ; Mesothelioma/*epidemiology/etiology ; Occupational Exposure ; Registries ; Risk ; }, abstract = {The purpose of the SENTIERI-ReNaM Project is to analyse the incidence of mesothelioma in Italian National Priority Contaminated Sites (NPCSs) in order to estimate the health impact of asbestos on resident populations, disentangling the role of occupational and environmental exposures. SENTIERI Project has provided the relevant information on geographic and demographic structure of NPCSs and on existing sources of contamination. The Italian National Mesothelioma Registry (ReNaM), that covers the whole country through its Regional Operational Centres (CORs), has made available the procedures for estimating the incidence of mesothelioma in NPCSs and for assessing occupational and environmental asbestos exposure of the individual cases. The synergy between these two epidemiological surveillance systems lay also the ground for communication programmes with the affected communities.}, } @article {pmid27825195, year = {2016}, author = {, }, title = {[SENTIERI - Epidemiological study of residents in national priority contaminated sites: incidence of mesothelioma].}, journal = {Epidemiologia e prevenzione}, volume = {40}, number = {5Suppl1}, pages = {1-116}, doi = {10.19191/EP16.5S1.P001.097}, pmid = {27825195}, issn = {1120-9763}, mesh = {Asbestos/toxicity ; Carcinogens, Environmental/toxicity ; Confidence Intervals ; *Environmental Exposure ; *Environmental Pollution ; Female ; *Hazardous Waste Sites ; Health Surveys ; Humans ; Incidence ; Industry ; Italy ; Male ; Mesothelioma/*epidemiology/etiology ; Occupational Exposure ; Registries ; Risk ; }, abstract = {The purpose of SENTIERI-ReNaM Project is to describe mesothelioma incidence in the Italian National Priority Contaminated Sites (NPCSs). The present report deals with 39 NPCSs (20 in Northern Italy, 8 in Central Italy and 11 in Southern Italy). Asbestos is specifically mentioned in the regulatory acts of recognition for 10 NPCSs and it is the only agent that has determined environmental contamination in 3 of them (Casale Monferrato, Broni, and Bari). The timeframe of the study is 2000-2011 for 34 out of 39 sites. The corresponding reference periods for the sites of Latium, Campania, Umbria, and Bolzano Province are, respectively, 2001-2011, 2005-2011, and 2006-2011. Standardized Incidence Ratios (SIRs) for mesothelioma, with their corresponding 90% Confidence Intervals, have been estimated for all sites. The interpretation of the study findings has been based on anamnestic information made available by the Italian National Mesothelioma Registry (ReNaM), and completed thanks to knowledge derived from the international scientific literature. In men, mesothelioma incidence has shown excesses in 27/39 sites and defects in the remaining 12; in women, excesses have been reported in 20 sites, defects in 15, and no cases have been detected in the remaining 4 sites. The highest annual incidence rates have been observed in the sites characterized only by the presence of asbestos- cement factories (Broni and Casale Monferrato): respectively, 98.0 and 68.6 per 100,000 per year in men, 72.1 and 45.8 in women. Besides these two sites, the highest rates have been observed in the sites with naval shipyards: 13.2 in men and 2.5 in women. Excesses of mesothelioma incidence have been confirmed (with respect to previous observations) in the sites of Broni, Casale Monferrato, Balangero, and in the coastal areas of Trieste, La Spezia, Venice, and Leghorn. Balangero has been the major European chrysotile quarry, while the other sites are characterized by the presence of naval shipyards with demonstrated use of asbestos before it was banned in 1992. An excess of mesothelioma incidence has also been confirmed in the site of Biancavilla, characterized by the presence of the fluoro-edenite fibrous amphibole, classified as carcinogenic to humans by the International Agency for Research on Cancer (IARC). An increased incidence of mesothelioma was also observed in the areas where no direct use of asbestos had previously been documented, like Cengio and Saliceto (chemical industry), Falconara on Sea (oil refinery), and Litorale Domizio Flegreo and Agro Aversano (a large area including multiple hazardous waste dumping sites). These findings show that a relevant proportion of Italian mesothelioma cases is concentrated in NPCSs. About 1,500 extra cases of mesothelioma have been estimated in the overall series of 39 sites (2000-2011), corresponding to 125 extra cases per year. The excess has concerned the sites with manufacture of asbestos-cement products, but also the areas with asbestos quarries, naval shipyards, illegal hazardous waste dumping sites with asbestos-containing materials, petrochemical industries, refineries and steel plants. In some sites, particularly Casale Monferrato and Broni, analytical epidemiological studies have shown the causal role of not only occupational, but also environmental exposures, with special reference to paving of gardens and courtyards with asbestos-cement industry by-products. The main novelty generated by the collaborative SENTIERI-ReNaM Project concerns the detection of significant mesothelioma excesses not only in sites where asbestos is explicitly reported as a source of contamination, but also in a number of areas defined "of national interest" for environmental cleanup due to other sources of pollution. This confirms that the range of economic activities and working and living environments affected by asbestos exposure is very wide and it is not restricted to the industrial sectors characterized by the direct use of this material.}, } @article {pmid27822122, year = {2016}, author = {Beebe-Dimmer, JL and Fryzek, JP and Yee, CL and Dalvi, TB and Garabrant, DH and Schwartz, AG and Gadgeel, S}, title = {Mesothelioma in the United States: a Surveillance, Epidemiology, and End Results (SEER)-Medicare investigation of treatment patterns and overall survival.}, journal = {Clinical epidemiology}, volume = {8}, number = {}, pages = {743-750}, pmid = {27822122}, issn = {1179-1349}, abstract = {INTRODUCTION: Mesothelioma is a rare malignancy typically associated with exposure to asbestos and poor survival. The purpose of this investigation was to describe mesothelioma patient characteristics, treatment patterns, and overall survival (OS) utilizing the National Cancer Institute's Surveillance, Epidemiology, and End Results-Medicare database.

MATERIALS AND METHODS: Patients in this study were diagnosed with malignant mesothelioma of the pleura or peritoneum between January 1, 2005 and December 31, 2009 with follow-up for survival through December 31, 2010. We examined both patient and tumor characteristics at time of diagnosis and subsequent treatment patterns (surgery, radiation, and chemotherapy). Among patients treated with chemotherapy, we determined chemotherapy regimen and OS by line of therapy.

RESULTS: Of the 1,625 patients considered eligible for this investigation, the median age at diagnosis was 78 years. Nearly a third of patients (30%) had surgery as part of their treatment and 45% were given chemotherapy. The median OS was 8 months (range 1-69 months). Among chemotherapy patients, the most commonly (67%) prescribed regimen for first-line therapy was cisplatin or carboplatin (Ca/Ci) combined with pemetrexed (Pe). Among those prescribed Ca/Ci + Pe as first-line therapy, retreatment with Ca/Ci + Pe (28%) or treatment with gemcitabine (30%) were the most common second-line therapies. Median OS for those receiving first-line chemotherapy was 7 months, and among those receiving second-line therapy median OS was extended an additional 5 months.

CONCLUSION: Irrespective of surgical resection, mesothelioma patients receiving some form of chemotherapy survived longer than patients who did not, with an additional survival benefit among those patients receiving multimodal treatment.}, } @article {pmid27821674, year = {2017}, author = {Merler, E and Somigliana, A and Girardi, P and Barbieri, PG}, title = {Residual fibre lung burden among patients with pleural mesothelioma who have been occupationally exposed to asbestos.}, journal = {Occupational and environmental medicine}, volume = {74}, number = {3}, pages = {218-227}, doi = {10.1136/oemed-2015-103382}, pmid = {27821674}, issn = {1470-7926}, mesh = {Aged ; Aged, 80 and over ; Asbestos/*adverse effects/*isolation & purification ; Female ; Humans ; Interviews as Topic ; Italy ; Lung/*pathology ; Lung Neoplasms/chemically induced/*pathology ; Male ; Mesothelioma/chemically induced/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Mineral Fibers ; Occupational Diseases/chemically induced/*pathology ; Occupational Exposure/*adverse effects/analysis ; }, abstract = {OBJECTIVES: To evaluate the lungs asbestos fibres concentration in participants with malignant pleural mesothelioma (MPM) who have been occupationally exposed.

METHODS: The lung samples were obtained from pleuropneumonectomies or autopsies of 271 male MPMs. The lung samples were examined through scanning electron microscopy. Retrospective assessment was used to assess for asbestos exposure. This study includes 248 MPMs with an occupational exposure defined as either 'definite' or 'probable' or 'possible'.

RESULTS: The participants had finished working in asbestos exposure conditions more than 20 years ago (on average 26.1±11.0 years). The fibre burden resulted with a geometric mean equal to 2.0 (95% CI 1.6 to 2.4) million fibres per gram of dry lung tissue. The burden was higher among participants employed in asbestos textiles industry and in shipyards with insulation material, if compared with construction workers or non-asbestos textile workers or participants working in chemicals or as auto mechanics. 91.3% of MPMs had a detectable amount of amphibole fibres. A strong lung clearance capability was evident among workers exposed to chrysotile fibres. Owing to that, the 1997 Helsinki Criteria for occupational exposure were reached in <35% of cases among participant working in construction, in metallurgical industry, in chemical or textile industry and among those performing brake repair activities.

CONCLUSIONS: The MPM cases are now occurring in Italy in participants who ceased occupational asbestos exposure decades before the analysis. A large majority still shows a residual content of amphibole fibres, but given the lung clearance capability, attribution to occupational exposure cannot rely only on fibres detection.}, } @article {pmid27819788, year = {2016}, author = {Gopar-Nieto, R and Cabello-López, A and Juárez-Pérez, CA and Haro-García, LC and Jiménez-Ramírez, C and Aguilar-Madrid, G}, title = {[Update on epidemiology, pathophysiology, diagnosis and treatment of malignant pleural mesothelioma].}, journal = {Revista medica del Instituto Mexicano del Seguro Social}, volume = {54}, number = {6}, pages = {770-776}, pmid = {27819788}, issn = {2448-5667}, mesh = {Combined Modality Therapy ; Humans ; *Mesothelioma/diagnosis/epidemiology/physiopathology/therapy ; Mexico/epidemiology ; *Occupational Diseases/diagnosis/epidemiology/physiopathology/therapy ; Palliative Care ; *Pleural Neoplasms/diagnosis/epidemiology/physiopathology/therapy ; }, abstract = {Malignant pleural mesothelioma is an occupational tumor caused by asbestos exposure. In Mexico, as asbestos usage is not prohibited, an increase in the number of cases is expected. Asbestos exposure is ubiquitous due to the great amount of products in which it is present. Its carcinogenicity is caused as the inhaled asbestos fibers cannot be eliminated by macrophages and, thus, they travel to the pleura through lymphatic pathways, producing a persistent inflammatory response. Diagnosis approach includes occupational history, along with clinical signs and symptoms, and paraclinical studies, such as pleural fluid cytology, chest x-rays, computed tomography, magnetic resonance imaging, and biopsy with immunohistochemistry. The main differential diagnosis is lung adenocarcinoma. Regarding the treatment of this tumor, it mainly comprises palliative care, even though chemotherapy, radiotherapy, and, in selected cases, surgical treatments have been used. There is an urgent need for general physicians and specialists to identify asbestos exposure, in order to make a timely diagnosis. Research is necessary to develop screening and prompt diagnostic tools, along with an epidemiological surveillance program for the workers and the general population exposed to asbestos.}, } @article {pmid27813512, year = {2017}, author = {Joseph, NM and Chen, YY and Nasr, A and Yeh, I and Talevich, E and Onodera, C and Bastian, BC and Rabban, JT and Garg, K and Zaloudek, C and Solomon, DA}, title = {Genomic profiling of malignant peritoneal mesothelioma reveals recurrent alterations in epigenetic regulatory genes BAP1, SETD2, and DDX3X.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {30}, number = {2}, pages = {246-254}, pmid = {27813512}, issn = {1530-0285}, support = {DP5 OD021403/OD/NIH HHS/United States ; }, mesh = {Aged ; Aged, 80 and over ; Carcinogenesis/genetics/pathology ; DEAD-box RNA Helicases/*genetics ; *Epigenesis, Genetic ; Female ; Gene Expression Profiling ; Histone-Lysine N-Methyltransferase/*genetics ; Humans ; Lung Neoplasms/*genetics/pathology ; Male ; Mesothelioma/*genetics/pathology ; Mesothelioma, Malignant ; Middle Aged ; Peritoneal Neoplasms/*genetics/pathology ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; Young Adult ; }, abstract = {Malignant mesothelioma is a rare cancer that arises from the mesothelial cells that line the pleural cavity and less commonly from the peritoneal lining of the abdomen and pelvis. Most pleural mesotheliomas arise in patients with a history of asbestos exposure, whereas the association of peritoneal mesotheliomas with exposure to asbestos and other potential carcinogens is less clear, suggesting that the genetic alterations that drive malignant peritoneal mesothelioma may be unique from those in pleural mesothelioma. Treatment options for all malignant mesotheliomas are currently limited, with no known targeted therapies available. To better understand the molecular pathogenesis of malignant peritoneal mesothelioma, we sequenced 510 cancer-related genes in 13 patients with malignant mesothelioma arising in the peritoneal cavity. The most frequent genetic alteration was biallelic inactivation of the BAP1 gene, which occurred in 9/13 cases, with an additional two cases demonstrating monoallelic loss of BAP1. All 11 of these cases demonstrated loss of BAP1 nuclear staining by immunohistochemistry, whereas two tumors without BAP1 alteration and all 42 cases of histologic mimics in peritoneum (8 multilocular peritoneal inclusion cyst, 6 well-differentiated papillary mesothelioma of the peritoneum, 16 adenomatoid tumor, and 12 low-grade serous carcinoma of the ovary) demonstrated intact BAP1 nuclear staining. Additional recurrently mutated genes in this cohort of malignant peritoneal mesotheliomas included NF2 (3/13), SETD2 (2/13), and DDX3X (2/13). While these genes are known to be recurrently mutated in pleural mesotheliomas, the frequencies are distinct in peritoneal mesotheliomas, with nearly 85% of peritoneal tumors harboring BAP1 alterations versus only 20-30% of pleural tumors. Together, these findings demonstrate the importance of epigenetic modifiers including BAP1, SETD2, and DDX3X in mesothelial tumorigenesis and suggest opportunities for targeted therapies.}, } @article {pmid27812913, year = {2016}, author = {Lowry, SJ and Weiss, NS}, title = {Geographic distribution of incidence of pericardial and paratesticular mesotheliomas in the USA.}, journal = {Cancer causes & control : CCC}, volume = {27}, number = {12}, pages = {1487-1489}, doi = {10.1007/s10552-016-0825-3}, pmid = {27812913}, issn = {1573-7225}, mesh = {Heart Neoplasms/epidemiology/pathology ; Humans ; Incidence ; Male ; Mesothelioma/*epidemiology/pathology ; Middle Aged ; Pericardium/pathology ; Pleural Neoplasms/epidemiology/pathology ; Registries ; SEER Program ; Testicular Neoplasms/*epidemiology/pathology ; United States/epidemiology ; }, abstract = {PURPOSE: Exposure to asbestos is thought to cause the large majority of pleural mesotheliomas in the USA. It is unknown whether asbestos exposure plays a role in the etiology of rarer forms of mesothelioma, e.g., those located in the pericardium or in the tunica vaginalis of the testis. In order to address this question, we sought to determine whether geographic patterns of incidence of these mesotheliomas have paralleled those of pleural mesotheliomas.

METHODS: We used age-adjusted incidence data from the nine populations served by the National Cancer Institute's Surveillance, Epidemiology, and End Results program during 1973-2011. Among men ages ≥50 years, we compared the incidence of pericardial and paratesticular mesotheliomas, respectively, with the incidence of pleural mesothelioma across the nine populations.

RESULTS: The rate of pleural mesothelioma was approximately twice as high in the San Francisco-Oakland (SFO) and Seattle-Puget Sound (SPS) areas compared to the other regions. In contrast, rates of paratesticular and pericardial mesotheliomas were not elevated in SFO (n = 3 paratesticular, 1 pericardial) or SPS (n = 4 paratesticular, 1 pericardial) relative to other regions.

CONCLUSIONS: The results of this ecologic study do not support a role for asbestos exposure in the etiologies of either pericardial or paratesticular mesotheliomas; however, this study was limited by small numbers and was unable to directly ascertain asbestos exposure.}, } @article {pmid27794408, year = {2016}, author = {Armato, SG and Blyth, KG and Keating, JJ and Katz, S and Tsim, S and Coolen, J and Gudmundsson, E and Opitz, I and Nowak, AK}, title = {Imaging in pleural mesothelioma: A review of the 13th International Conference of the International Mesothelioma Interest Group.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {101}, number = {}, pages = {48-58}, pmid = {27794408}, issn = {1872-8332}, support = {ETM/285/CSO_/Chief Scientist Office/United Kingdom ; R01 CA193556/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Congresses as Topic ; Humans ; Lung Neoplasms/*diagnostic imaging/pathology ; Magnetic Resonance Imaging/methods ; Male ; Mesothelioma/*diagnostic imaging/pathology ; Mesothelioma, Malignant ; Middle Aged ; Neoplasm Staging ; Pleural Neoplasms/*diagnostic imaging/pathology ; Radionuclide Imaging/*methods ; Response Evaluation Criteria in Solid Tumors ; Spectroscopy, Near-Infrared ; Tomography, Emission-Computed ; Tumor Burden ; United Kingdom ; }, abstract = {Imaging plays an important role in the detection, diagnosis, staging, response assessment, and surveillance of malignant pleural mesothelioma. The etiology, biology, and growth pattern of mesothelioma present unique challenges for each modality used to capture various aspects of this disease. Clinical implementation of imaging techniques and information derived from images continue to evolve based on active research in this field worldwide. This paper summarizes the imaging-based research presented orally at the 2016 International Conference of the International Mesothelioma Interest Group (iMig) in Birmingham, United Kingdom, held May 1-4, 2016. Presented topics included intraoperative near-infrared imaging of mesothelioma to aid the assessment of resection completeness, an evaluation of tumor enhancement improvement with increased time delay between contrast injection and image acquisition in standard clinical magnetic resonance imaging (MRI) scans, the potential of early contrast enhancement analysis to provide MRI with a role in mesothelioma detection, the differentiation of short- and long-term survivors based on MRI tumor volume and histogram analysis, the response-assessment potential of hemodynamic parameters derived from dynamic contrast-enhanced computed tomography (DCE-CT) scans, the correlation of CT-based tumor volume with post-surgical tumor specimen weight, and consideration of the need to update the mesothelioma tumor response assessment paradigm.}, } @article {pmid27793915, year = {2016}, author = {Jennings, CJ and Zainal, N and Dahlan, IM and Kay, EW and Harvey, BJ and Thomas, W}, title = {Tamoxifen Suppresses the Growth of Malignant Pleural Mesothelioma Cells.}, journal = {Anticancer research}, volume = {36}, number = {11}, pages = {5905-5913}, doi = {10.21873/anticanres.11177}, pmid = {27793915}, issn = {1791-7530}, mesh = {Antineoplastic Agents, Hormonal/*pharmacology ; Apoptosis/drug effects ; Cell Line, Tumor ; Cell Proliferation/*drug effects ; Cisplatin/administration & dosage ; Cyclin-Dependent Kinases/antagonists & inhibitors ; Humans ; Mesothelioma/*pathology ; Pleural Neoplasms/*pathology ; Tamoxifen/administration & dosage/*pharmacology ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is a rare but highly aggressive malignancy most often associated with exposure to asbestos. Recent evidence points to oestrogen receptor (ER)-β having a tumour-suppressor role in MPM progression, and this raises the question of whether selective modulators of ERs could play a role in augmenting MPM therapy.

MATERIALS AND METHODS: We investigated the action of tamoxifen in inhibiting the growth and modulating the cisplatin sensitivity of four MPM cell lines.

RESULTS: Tamoxifen inhibited the growth of MPM cells and also modulated their sensitivity to cisplatin. The MPM cell lines expressed ERβ, but the actions of tamoxifen were not blocked by antagonism of nuclear ERs. Tamoxifen treatment repressed the expression of cyclins by MPM cells, resulting in cell-cycle arrest and caspase-3-coupled apoptosis signaling.

CONCLUSION: The ER-independent actions of tamoxifen on MPM cell proliferation and cell-cycle progression may have clinical benefits for a subset of patients with MPM.}, } @article {pmid27785864, year = {2016}, author = {Terracini, B and Mirabelli, D and Baur, X and Landrigan, PJ and Ramazzini, C}, title = {Re: Comments on the causation of malignant mesothelioma: Rebutting the false concept that recent exposures to asbestos do not contribute to causation of mesothelioma.}, journal = {American journal of industrial medicine}, volume = {59}, number = {12}, pages = {1180-1182}, doi = {10.1002/ajim.22663}, pmid = {27785864}, issn = {1097-0274}, mesh = {Asbestos ; Humans ; *Lung Neoplasms ; *Mesothelioma ; }, } @article {pmid27783867, year = {2017}, author = {Harada, A and Uchino, J and Harada, T and Nakagaki, N and Hisasue, J and Fujita, M and Takayama, K}, title = {Vascular endothelial growth factor promoter-based conditionally replicative adenoviruses effectively suppress growth of malignant pleural mesothelioma.}, journal = {Cancer science}, volume = {108}, number = {1}, pages = {116-123}, pmid = {27783867}, issn = {1349-7006}, mesh = {Adenoviridae/genetics/*growth & development ; Animals ; Cell Death ; Cell Line, Tumor ; Female ; Humans ; Lung Neoplasms/*pathology/*therapy/virology ; Mesothelioma/*pathology/*therapy/virology ; Mesothelioma, Malignant ; Mice ; Mice, Nude ; *Oncolytic Virotherapy ; Pleural Neoplasms/pathology/*therapy/virology ; Promoter Regions, Genetic/*genetics ; Transgenes/genetics ; Vascular Endothelial Growth Factor A/*genetics/metabolism ; Virus Replication/*genetics ; Xenograft Model Antitumor Assays ; }, abstract = {Malignant mesothelioma (MM) incidence is increasing drastically worldwide as an occupational disease resulting from asbestos exposure. However, no curative treatment for MM of advanced stage is available. Thus, new therapeutic approaches for MM are required. Because malignant pleural mesothelioma (MPM) cells spread along the pleural surface in most patients, MPM can be targeted using intrapleural therapeutic approaches. In this study, we investigated the effectiveness of the intrapleural instillation of a replication-competent adenovirus as an oncolytic agent against MPM. We constructed a vascular endothelial growth factor promoter-based conditionally replicative adenovirus (VEGF-CRAd) that replicates exclusively in VEGF-expressing cells. All of the MM cell lines that we tested expressed VEGF mRNA, and VEGF-CRAd selectively replicated in these MM cells and exerted a direct concentration-dependent oncolytic effect in vitro. Furthermore, our in vivo studies showed that pre-infection of MM cells with VEGF-CRAd potently suppressed MPM tumor formation in nude mice, and that intrapleural instillation of VEGF-CRAd prolonged the survival time of tumor-bearing mice. Our results indicate that VEGF-CRAd exerts an oncolytic effect on MM cells and that intrapleural instillation of VEGF-CRAd is safe and might represent a promising therapeutic strategy for MPM.}, } @article {pmid27761727, year = {2017}, author = {Sahin, N and Akatli, AN and Celik, MR and Ulutas, H and Samdanci, ET and Colak, C}, title = {The Role of CD90 in the Differential Diagnosis of Pleural Malignant Mesothelioma, Pulmonary Carcinoma and Comparison with Calretının.}, journal = {Pathology oncology research : POR}, volume = {23}, number = {3}, pages = {487-491}, pmid = {27761727}, issn = {1532-2807}, mesh = {Adenocarcinoma/*metabolism/pathology ; Adenocarcinoma of Lung ; Biomarkers, Tumor/metabolism ; Calbindin 2/*metabolism ; Carcinoma, Squamous Cell/metabolism/pathology ; Diagnosis, Differential ; Female ; Humans ; Lung Neoplasms/*metabolism/pathology ; Male ; Mesothelioma/*metabolism/pathology ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/*metabolism/pathology ; Sensitivity and Specificity ; Thy-1 Antigens/*metabolism ; }, abstract = {Pleural Malignant Mesothelioma (MM) is a fatal disease that has been associated with asbestos exposure. Differential diagnosis between the pleural infiltration of pulmonary carcinomas and MM is rather difficult particularly for epitheloid type mesothelioma.We aimed to investigate the utility of CD90, a cancer stem cell marker, in the differential diagnosis of MM and lung carcinoma, its prognostic significance and compare its value with that of Calretinin. Ninety pathology specimens including MM (n:30), pulmonary adenocarcinoma (n:30) and pulmonary squamous cell carcinoma (n:30) were used in this study. Immunohistochemical comparision of CD 90 and Calretinin was made in all groups. Calretinin was positive in 20 cases with MM (64.5 %), and was negative in 10 (32.3 %). CD 90 was positive in 25 of these cases (80 %) and negative in 5 (16 %). On the other hand pulmonary adenocarcinomas and squamous cell carcinomas showed positivity with CD90, 63,6 % and 73 %, respectively. We think that CD 90 has no place in the differential diagnosis between mesothelioma and pulmonary carcinoma because of the low specificity in spite of the high sensitivity.}, } @article {pmid27751355, year = {2016}, author = {Ascoli, V and Cozzi, I and Vatrano, S and Izzo, S and Giorcelli, J and Romeo, E and Carnovale-Scalzo, C and Grillo, LR and Facciolo, F and Visca, P and Papotti, M and Righi, L}, title = {Mesothelioma families without inheritance of a BAP1 predisposing mutation.}, journal = {Cancer genetics}, volume = {209}, number = {9}, pages = {381-387}, doi = {10.1016/j.cancergen.2016.07.002}, pmid = {27751355}, issn = {2210-7762}, mesh = {Aged ; Female ; *Genetic Predisposition to Disease ; Humans ; Male ; Mesothelioma/*genetics ; Middle Aged ; *Mutation ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {Familial malignant mesothelioma clusters are ideal candidates to explore BAP1 genomic status as a predisposing risk factor. We report data on BAP1 analysis in four families with multiple mesothelioma cases to investigate possible BAP1 alterations associated with an inherited cancer syndrome. We also recorded family history of cancer and assessed asbestos exposure. By genomic direct sequencing, we found no evidence of a BAP1 germline mutation in tumor DNA samples (one mesothelioma per family: n = 3 epithelioid; n = 1 biphasic). On the other hand, we identified a novel BAP1 somatic alteration (c.329_335delinsTC) in exon 5 (n = 1 biphasic), and we hypothesized the occurrence of somatic inactivating events not identifiable by sequencing in the other cases (n = 3 epithelioid), as demonstrated by the loss of nuclear BAP1 immunostaining. History of other cancers was in sites not typical of the BAP1 cancer syndrome. Asbestos exposure was occupational (n = 2 clusters), household (n = 1), and unknown (n = 1). These family units without inheritance of a BAP1 predisposing mutation expand the number of unmutated germline BAP1 families with multiple mesothelioma cases. This suggests that besides the exposure to asbestos other currently unknown genetic or epigenetic factors may be responsible for the high incidence of mesothelioma in BAP1-unmutated families.}, } @article {pmid27739317, year = {2016}, author = {Mrinakova, B and Kajo, K and Ondrusova, M and Simo, J and Ondrus, D}, title = {Malignant Mesothelioma of the Tunica Vaginalis Testis. A Clinicopathologic Analysis of Two Cases with a Review of the Literature.}, journal = {Klinicka onkologie : casopis Ceske a Slovenske onkologicke spolecnosti}, volume = {29}, number = {5}, pages = {369-374}, pmid = {27739317}, issn = {0862-495X}, mesh = {Adult ; Aged, 80 and over ; Humans ; Lung Neoplasms/*pathology/surgery ; Male ; Mesothelioma/*pathology/surgery ; Mesothelioma, Malignant ; Prognosis ; Testicular Hydrocele/*pathology/surgery ; Testicular Neoplasms/*pathology/surgery ; Young Adult ; }, abstract = {Paratesticular malignant mesothelioma is an extremely rare type of mesothelioma with only a limited number of reported cases. Its clinical differentiation is challenging, and its diagnosis is almost exclusively accidental. The major risk factor is exposure to asbestos, typically with a long latency between exposure and diagnosis. The current study presents the clinical data of two patients diagnosed with paratesticular malignant mesothelioma. We evaluated a large spectrum of risk factors in the patients histories. The histomorphological and immunohistochemical characteristics were analysed and put into the perspective of a broad differential diagnosis. Both cases of malignant epithelial mesothelioma of the tunica vaginalis testis clinically presented as unilateral hydroceles. Patients underwent surgery with the perioperative finding of a tumour. Radical inguinal orchiectomy was the treatment of choice for both patients. After comprehensive staging, the second patient underwent a second step of inguinal and pelvic lymph node dis- section. Follow-up visits revealed recurrence of the disease in the first patient. Resection of the tumour was performed. The histology confirmed the relapse of a tumour with identical features to those of the first tumour. Chemotherapy and radiotherapy were not indicated. Both patients are currently in complete remission. In conclusion, surgical treatment had a determinative role in the prognosis of these patients. Radical orchiectomy is the treatment of choice for localized disease. Lymph node dissection can be considered in the case of lymph node enlargement. There is a lack of evidence-based data for adjuvant chemotherapy and radiotherapy. Patients should be referred to experienced multidisciplinary cancer centres for a second opinion on histology, treatment, and a follow-up plan.Key words: mesothelioma - tunica vaginalis testis - hydrocele - asbestos exposure.}, } @article {pmid27734057, year = {2016}, author = {Armstrong, B and Driscoll, T}, title = {Mesothelioma in Australia: cresting the third wave.}, journal = {Public health research & practice}, volume = {26}, number = {2}, pages = {}, doi = {10.17061/phrp2621614}, pmid = {27734057}, issn = {2204-2091}, mesh = {Air Pollutants/*toxicity ; Asbestos/*toxicity ; Australia/epidemiology ; Construction Materials ; Environmental Exposure/*adverse effects ; Environmental Monitoring ; Housing ; Humans ; Incidence ; Mesothelioma/*epidemiology ; Occupational Diseases/*epidemiology ; Occupational Exposure/*adverse effects ; Registries ; }, abstract = {There has been much recent commentary about the 'third wave' of asbestos-related disease, arising particularly from exposures of people repairing, renovating or demolishing buildings that contain asbestos. The presence and extent of a third wave, however, are difficult to assess, and the extent and risk of both occupational and nonoccupational third-wave exposures are largely unmeasured. Moreover, we lack information on the extent of deterioration of in situ asbestos, and its significance for ambient and third-wave exposures. This paper considers the available evidence about the third wave. It proposes approaches to obtaining the information needed to properly estimate the risk of third-wave exposures, and guide actions that will crest a likely third wave with minimum harm and cost to the community.}, } @article {pmid27716620, year = {2016}, author = {Bononi, I and Comar, M and Puozzo, A and Stendardo, M and Boschetto, P and Orecchia, S and Libener, R and Guaschino, R and Pietrobon, S and Ferracin, M and Negrini, M and Martini, F and Bovenzi, M and Tognon, M}, title = {Circulating microRNAs found dysregulated in ex-exposed asbestos workers and pleural mesothelioma patients as potential new biomarkers.}, journal = {Oncotarget}, volume = {7}, number = {50}, pages = {82700-82711}, pmid = {27716620}, issn = {1949-2553}, mesh = {Area Under Curve ; Asbestos/*adverse effects ; Biomarkers, Tumor/*blood/genetics ; Case-Control Studies ; Circulating MicroRNA/*blood/genetics ; Gene Expression Profiling/methods ; Humans ; Lung Neoplasms/*blood/genetics/pathology ; Mesothelioma/*blood/genetics/pathology ; Mesothelioma, Malignant ; MicroRNAs/blood/genetics ; Occupational Exposure/*adverse effects ; *Occupational Health ; Oligonucleotide Array Sequence Analysis ; Pleural Neoplasms/*blood/genetics/pathology ; Predictive Value of Tests ; ROC Curve ; Real-Time Polymerase Chain Reaction ; Reproducibility of Results ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {Malignant pleural mesothelioma (MPM), a fatal cancer, is an occupational disease mostly affecting workers ex-exposed to asbestos fibers. The asbestos, a cancerogenic mineral of different chemical composition, was widely employed in western Countries in industrial manufactures of different types. MPM may arise after a long latency period, up to five decades. MPM is resistant to conventional chemo- and radio-therapies. Altogether, these data indicate that the identification of new and specific markers are of a paramount importance for an early diagnosis and treatment of MPM. In recent years, microRNAs expression was found dysregulated in patients, both in cancer cells and sera, affected by tumors of different histotypes, including MPM. Cell and circulanting microRNAs, found to be dysregulated in this neoplasia, were proposed as new biomarkers. It has been reported that circulating microRNAs are stable in biological fluids and could be employed as potential MPM biomarkers. In this investigation, circulating microRNAs (miR) from serum samples of MPM patients and workers ex-exposed to asbestos fibers (WEA) and healthy subjects (HS) were comparatively analyzed by microarray and RT-qPCR technologies. Our results allowed (i) to select MiR-3665, an endogenous stable microRNA, as the internal control to quantify in our analyses circulating miRNAs; to detect (ii) miR-197-3p, miR-1281 and miR 32-3p up-regulated in MPM compared to HS; (iii) miR-197-3p and miR-32-3p up-regulated in MPM compared to WEA; (iv) miR-1281 up-regulated in both MPM and WEA compared to HS. In conclusion, three circulating up-regulated microRNAs, i.e. miR-197-3p, miR-1281 and miR-32-3p are proposed as potential new MPM biomarkers.}, } @article {pmid27714389, year = {2016}, author = {Korda, RJ and Clements, MS and Armstrong, BK and Trevenar, SM and Chalker, EB and Newman, LA and Kirk, MD}, title = {Mesothelioma trends in the ACT and comparisons with the rest of Australia.}, journal = {Public health research & practice}, volume = {26}, number = {4}, pages = {}, doi = {10.17061/phrp2641646}, pmid = {27714389}, issn = {2204-2091}, mesh = {Australian Capital Territory/epidemiology ; Female ; Humans ; Male ; Mesothelioma/*epidemiology ; Poisson Distribution ; Registries ; }, abstract = {OBJECTIVES: Inhalation of asbestos fibres is the predominant cause of malignant mesothelioma. Domestic exposure to asbestos is a major community concern in the Australian Capital Territory (ACT) because of loose-fill asbestos home insulation. Little is known about how trends in mesothelioma rates in the ACT compare with those elsewhere. The objective of this study was to describe trends in mesothelioma rates in the ACT and compare them with those for the rest of Australia.

METHODS: We used de-identified data from the ACT Cancer Registry (1982- 2014), and the Western Australia (WA) Cancer Registry and the Australian Cancer Database (1982-2011). We calculated crude mesothelioma rates, by 3-year periods, for the ACT and for the rest of Australia (excluding WA). We used Poisson regression to analyse mesothelioma trends from 1994 to 2011 (complete reporting period) using an indirect standardisation approach to adjust for age and sex.

RESULTS: There were 140 mesothelioma cases reported to the ACT Cancer Registry between 1982 and 2014 - 81% male and 19% female. Between 1994 and 2011, age- and sex-adjusted mesothelioma rates in the ACT increased over time, on average by 12% per 3-year period (relative risk [RR] 1.12; 95% confidence interval [CI] 0.99, 1.26). Compared with the rest of Australia (excluding WA), ACT rates were, on average, lower (RR 0.84; 95% CI 0.69, 1.02), but they increased at a higher rate (RR 1.12 per 3-year period; 95% CI 0.99, 1.27). These results are strongly influenced by the higher rate of mesothelioma observed in the ACT in 2009-2011, when ACT rates became similar to those for the rest of Australia (excluding WA).

CONCLUSIONS: Although mesothelioma rates may have increased more in the ACT than the rest of Australia (excluding WA) during the past two decades, there is considerable uncertainty in the trends. More information is needed regarding the health risks associated with living in a house with loose-fill asbestos insulation. This is the subject of further studies within the ACT Asbestos Health Study.}, } @article {pmid27705551, year = {2016}, author = {Dodson, RF}, title = {Preface: Respirable elongated mineral particles and human health-Revisited.}, journal = {Journal of toxicology and environmental health. Part B, Critical reviews}, volume = {19}, number = {5-6}, pages = {149-150}, doi = {10.1080/10937404.2016.1193358}, pmid = {27705551}, issn = {1521-6950}, mesh = {Asbestos/*toxicity ; Humans ; Mesothelioma/*chemically induced ; }, } @article {pmid27705550, year = {2016}, author = {Levin, JL and Rouk, A and Shepherd, S and Hurst, GA and McLarty, JW}, title = {Tyler asbestos workers: A mortality update in a cohort exposed to amosite.}, journal = {Journal of toxicology and environmental health. Part B, Critical reviews}, volume = {19}, number = {5-6}, pages = {190-200}, doi = {10.1080/10937404.2016.1195319}, pmid = {27705550}, issn = {1521-6950}, mesh = {Asbestos, Amosite/*toxicity ; Asbestosis/etiology/*mortality ; Cohort Studies ; Female ; Humans ; Male ; Occupational Diseases/chemically induced/*mortality ; *Occupational Exposure ; Texas/epidemiology ; }, abstract = {The Tyler asbestos plant produced pipe insulation from 1954 to 1972 and exclusively used amosite asbestos. There were 1130 former workers of this plant during the period of operation. A death certificate mortality analysis was published regarding this plant in 1998 for the period through 1993. This study represents an update of the mortality analysis with additional certificates collected for deaths occurring through 2011.Searches of the National Death Index database were conducted in 2004 and again in 2013. At the time of the latter search, only deaths occurring through 2011 were available. In total, 265 distinct additional death certificates were secured and added to 304 available from the original study. After the new certificates were coded (ICD-9), data were analyzed using the Centers for Disease Control and Prevention Life Table Analysis System (LTAS) and standard mortality ratios (SMR) generated with 95% confidence limits (CL). LTAS constructs cause-specific mortality rates by age, gender, race, and person-time at risk, and compares observed rates with a referent population in order to derive SMR. A significant excess number of deaths due to nonmalignant respiratory disease (asbestosis) and from select malignant neoplasms were identified. There were in total 23 mesothelioma deaths (4% of deaths), with 16 pleural and 7 peritoneal. The SMR for malignant neoplasms of the trachea, bronchus, and lung was 244 (with 95% CL 196, 300), suggesting that exposed workers from this cohort were nearly 2.5-fold (244 %) more likely to die from this cause as the general referent population. The analysis also showed that exposures of short duration (<6 mo) produced significantly elevated SMR for all respiratory cancers, lung cancer, and pleural mesothelioma. There was a significant difference in median duration of exposure for mesothelioma types, confirming association of peritoneal mesothelioma with longer duration of exposure. Deaths due to intestinal cancer (predominantly colon; not including rectum) were also found in excess. The mortality experience of the Tyler cohort continues to be followed with great interest, given the exclusivity of exposure to amosite. Data confirm the inherent pathogenicity of this fiber type for nonmalignant disease as well as select cancers, particularly relevant given the importance of this amphibole's use in the United States.}, } @article {pmid27705549, year = {2016}, author = {Lemen, RA}, title = {Mesothelioma from asbestos exposures: Epidemiologic patterns and impact in the United States.}, journal = {Journal of toxicology and environmental health. Part B, Critical reviews}, volume = {19}, number = {5-6}, pages = {250-265}, doi = {10.1080/10937404.2016.1195323}, pmid = {27705549}, issn = {1521-6950}, mesh = {Asbestos/*toxicity ; *Environmental Exposure ; Humans ; Incidence ; Mesothelioma/*epidemiology/etiology ; Occupational Exposure ; Socioeconomic Factors ; United States/epidemiology ; }, abstract = {Mesothelioma, a rare tumor, is highly correlated with asbestos exposure. Mesothelioma, similar to all asbestos-related diseases, is dose/intensity dependent to some degree, and studies showed the risk of mesothelioma rises with cumulative exposures. Multiple processes occur in an individual before mesothelioma occurs. The impact of mesothelioma in the United States has been continuous over the last half century, claiming between 2,000 and 3,000 lives each year. Mesothelioma is a preventable tumor that is more frequently reported as associated with asbestos exposure among men than women. However, the rate of asbestos-associated mesothelioma is on the rise among women due to better investigation into their histories of asbestos exposure. It is of interest that investigators detected asbestos-associated cases of mesothelioma in women from nonoccupational sources-that is, bystander, incidental, or take-home exposures. It is postulated that asbestos-associated mesotheliomas, in both men and women, are likely underreported. However, with the implementation of the most recent ICD-10 coding system, the correlation of mesothelioma with asbestos exposure is expected to rise to approximately 80% in the United States. This study examined the demographic and etiological nature of asbestos-related mesothelioma.}, } @article {pmid27705548, year = {2016}, author = {Cook, PM and Swintek, J and Dawson, TD and Chapman, D and Etterson, MA and Hoff, D}, title = {Quantitative structure-mesothelioma potency model optimization for complex mixtures of elongated particles in rat pleura: A retrospective study.}, journal = {Journal of toxicology and environmental health. Part B, Critical reviews}, volume = {19}, number = {5-6}, pages = {266-288}, doi = {10.1080/10937404.2016.1195326}, pmid = {27705548}, issn = {1521-6950}, mesh = {Animals ; Asbestos/*toxicity ; Complex Mixtures/*toxicity ; Dose-Response Relationship, Drug ; Mesothelioma/*chemically induced ; Models, Theoretical ; Pleural Neoplasms/*chemically induced ; Rats ; Retrospective Studies ; }, abstract = {Cancer potencies of mineral and synthetic elongated particle mixtures, including asbestos fibers, are influenced by changes in fiber dose composition, bioavailability, and biodurability in combination with relevant cytotoxic dose-response relationships. An extensive rat intrapleural dose characterization data set with a wide variety of elongated particles physicochemical properties facilitated statistical analyses of pleural mesothelioma response data combined from several studies for evaluation of alternative dose-response models. Utilizing logistic regression of individual elongated particle dimensional variations within each test sample, four major findings emerged: (1) Mild acid leaching provides superior prediction of tumor incidence compared to samples that were not leached; (2) sum of the elongated particle surface areas from mildly acid-leached samples provides the optimum holistic dose-response model; (3) progressive removal of dose associated with very short and/or thin elongated particles significantly degrades the resultant particle count and surface area dose-based predictive model fits; and (4) alternative biologically plausible model adjustments provide evidence for reduced potency of elongated particles with aspect ratios less than 8 and lengths greater than 80 µm. Regardless of these adjustments, the optimum predictive models strongly incorporate potency attributable to abundant short elongated particles in proportion to their surface area. Transmission electron microscopy analyses of low-temperature-ashed pleural membrane and lung tissues 5.5 mo post intrapleural exposures do not support hypotheses that short elongated particles that reach the pleural space are rapidly eliminated. Low-aspect-ratio elongated particles were still abundant in pleural membrane tissues but may have reduced potencies due to aggregation tendencies and therefore lower potential for intracellular presence.}, } @article {pmid27705546, year = {2016}, author = {Andujar, P and Lacourt, A and Brochard, P and Pairon, JC and Jaurand, MC and Jean, D}, title = {Five years update on relationships between malignant pleural mesothelioma and exposure to asbestos and other elongated mineral particles.}, journal = {Journal of toxicology and environmental health. Part B, Critical reviews}, volume = {19}, number = {5-6}, pages = {151-172}, doi = {10.1080/10937404.2016.1193361}, pmid = {27705546}, issn = {1521-6950}, mesh = {Asbestos/*toxicity ; *Environmental Exposure ; Humans ; *Lung Neoplasms/chemically induced/epidemiology/genetics ; *Mesothelioma/chemically induced/epidemiology/genetics ; Mesothelioma, Malignant ; Minerals/toxicity ; Nanoparticles/*toxicity ; Occupational Exposure ; *Pleural Neoplasms/chemically induced/epidemiology/genetics ; }, abstract = {Despite the reduction of global asbestos consumption and production due to the ban or restriction of asbestos uses in more than 50 countries since the 1970s, malignant mesothelioma remains a disease of concern. Asbestos is still used, imported, and exported in several countries, and the number of mesothelioma deaths may be expected to increase in the next decades in these countries. Asbestos exposure is the main risk factor for malignant pleural mesothelioma, but other types of exposures are linked to the occurrence of this type of cancer. Although recent treatments improve the quality of life of patients with mesothelioma, malignant pleural mesothelioma remains an aggressive disease. Recent treatments have not resulted in appreciable improvement in survival, and thus development of more efficient therapies is urgently needed. The development of novel therapeutic strategies is dependent on our level of knowledge of the physiopathological and molecular changes that mesothelial cells acquired during the neoplastic process. During the past 5 years, new findings have been published on the etiology, epidemiology, molecular changes, and innovative treatments of malignant pleural mesothelioma. This review aims to update the findings of recent investigations on etiology, epidemiology, and molecular changes with a focus on (1) attributable risk of asbestos exposure in men and women and (2) coexposure to other minerals and other elongated mineral particles or high aspect ratio nanoparticles. Recent data obtained on genomic and gene alterations, pathways deregulations, and predisposing factors are summarized.}, } @article {pmid27705545, year = {2016}, author = {Larson, D and Powers, A and Ambrosi, JP and Tanji, M and Napolitano, A and Flores, EG and Baumann, F and Pellegrini, L and Jennings, CJ and Buck, BJ and McLaurin, BT and Merkler, D and Robinson, C and Morris, P and Dogan, M and Dogan, AU and Pass, HI and Pastorino, S and Carbone, M and Yang, H}, title = {Investigating palygorskite's role in the development of mesothelioma in southern Nevada: Insights into fiber-induced carcinogenicity.}, journal = {Journal of toxicology and environmental health. Part B, Critical reviews}, volume = {19}, number = {5-6}, pages = {213-230}, pmid = {27705545}, issn = {1521-6950}, support = {P30 CA071789/CA/NCI NIH HHS/United States ; R01 CA160715/CA/NCI NIH HHS/United States ; R01 CA198138/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Epithelial Cells/cytology/*drug effects ; Lung Neoplasms/chemically induced/*pathology ; Magnesium Compounds/*toxicity ; Mesothelioma/chemically induced/*pathology ; Mesothelioma, Malignant ; Mice ; Mice, Inbred BALB C ; Nevada ; Silicon Compounds/*toxicity ; }, abstract = {Similar to asbestos fibers, nonregulated mineral fibers can cause malignant mesothelioma (MM). Recently, increased proportions of women and young individuals with MM were identified in southern Nevada, suggesting that environmental exposure to carcinogenic fibers was causing the development of MM. Palygorskite, a fibrous silicate mineral with a history of possible carcinogenicity, is abundant in southern Nevada. In this study, our aim was to determine whether palygorskite was contributing to the development of MM in southern Nevada. While palygorskite, in vitro, displayed some cytotoxicity toward primary human mesothelial (HM) cells and reduced their viability, the effects were roughly half of those observed when using similar amounts of crocidolite asbestos. No Balb/c (0/19) or MexTAg (0/18) mice injected with palygorskite developed MM, while 3/16 Balb/c and 13/14 MexTAg mice injected with crocidolite did. Lack of MM development was associated with a decreased acute inflammatory response, as injection of palygorskite resulted in lower percentages of macrophages (p = .006) and neutrophils (p = .02) in the peritoneal cavity 3 d after exposure compared to injection of crocidolite. Additionally, compared to mice injected with crocidolite, palygorskite-injected mice had lower percentages of M2 (tumor-promoting) macrophages (p = .008) in their peritoneal cavities when exposed to fiber for several weeks. Our study indicates that palygorskite found in the environment in southern Nevada does not cause MM in mice, seemingly because palygorskite, in vivo, fails to elicit inflammation that is associated with MM development. Therefore, palygorskite is not a likely contributor to the MM cases observed in southern Nevada.}, } @article {pmid27705544, year = {2016}, author = {Soeberg, MJ and Leigh, J and van Zandwijk, N}, title = {Malignant mesothelioma in Australia 2015: Current incidence and asbestos exposure trends.}, journal = {Journal of toxicology and environmental health. Part B, Critical reviews}, volume = {19}, number = {5-6}, pages = {173-189}, doi = {10.1080/10937404.2016.1194254}, pmid = {27705544}, issn = {1521-6950}, mesh = {Age Factors ; Asbestos/*toxicity ; Australia/epidemiology ; *Environmental Exposure ; Geography ; Humans ; Incidence ; Lung Neoplasms/chemically induced/*epidemiology ; Mesothelioma/chemically induced/*epidemiology ; Mesothelioma, Malignant ; Occupational Exposure ; Sex Factors ; }, abstract = {Australia is known to have had the highest per-capita asbestos consumption level of any nation, reaching a peak in the 1970s. Although crocidolite was effectively banned in the late 1960s, and amosite use ceased in the mid 1980s, a complete asbestos ban was not implemented until 2003. This resulted in an epidemic of asbestos-related disease, which has only now reached its peak. Between 1982 and 2011, 13,036 individuals were newly diagnosed with malignant mesothelioma, with 690 diagnosed in 2011. A further 778 cases were identified between 1945 and 1981 from retrospective searches and the first 2 years of the Australian Mesothelioma Program. The age-standardized malignant mesothelioma incidence rate has leveled off in the last 10 years (2.8 per 100,000 in 2011). There has been a marked increase over time in the age-specific incidence rates for individuals aged 75 years or older. Data from the current Australian Mesothelioma Registry on asbestos exposure history in Australia is available for 449 subjects diagnosed between July 1, 2010, and April 1, 2015. This asbestos exposure history data show that 60% (n = 268) of cases had probable or possible occupational asbestos exposure, with trade-based jobs being the most frequent sources of occupational asbestos exposure. In addition, out of the 449 cases, 377 were recorded as having probable or possible nonoccupational asbestos exposure. Continuous vigilance toward changes over time in the settings in which people are exposed to asbestos and in the descriptive epidemiology of malignant mesothelioma is recommended to enable a comprehensive understanding of the current and future impact of asbestos-related diseases in Australia.}, } @article {pmid27705543, year = {2016}, author = {Baumann, F and Carbone, M}, title = {Environmental risk of mesothelioma in the United States: An emerging concern-epidemiological issues.}, journal = {Journal of toxicology and environmental health. Part B, Critical reviews}, volume = {19}, number = {5-6}, pages = {231-249}, doi = {10.1080/10937404.2016.1195322}, pmid = {27705543}, issn = {1521-6950}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; *Environmental Exposure ; Female ; Humans ; Male ; Mesothelioma/chemically induced/*epidemiology ; Middle Aged ; Occupational Exposure ; Risk Assessment ; Sex Factors ; United States/epidemiology ; Young Adult ; }, abstract = {Despite predictions of decline in mesothelioma following the ban of asbestos in most industrial countries, the incidence is still increasing globally, particularly in women. Because occupational exposure to asbestos is the main cause of mesothelioma, it occurs four- to eightfold more frequently in men than women, at a median age of 74 years. When mesothelioma is due to an environmental exposure, the M:F sex ratio is 1:1 and the median age at diagnosis is ~60 years. Studying environmental risk of mesothelioma is challenging because of the long latency period and small numbers, and because this type of exposure is involuntary and unknown. Individual-based methods cannot be used, and new approaches need to be found. To better understand the most recent trends of mesothelioma in the United States, all mesothelioma deaths reported to the Centers for Disease Control and Prevention (CDC) during 1999-2010 were analyzed. Among all mesothelioma deaths in the United States, the 1920s birth cohort significantly predominated, and the proportion of younger cohorts constantly decreased with time, suggesting a decline in occupational exposure in these cohorts. The M:F mesothelioma sex ratio fell with time, suggesting an increased proportion of environmental cases. Environmental exposures occur in specific geographic areas. At the large scale of a state, mesotheliomas related to environmental exposure are diluted among occupational cases. The spatial analysis at a smaller scale, such as county, enables detection of areas with higher proportions of female and young mesothelioma cases, thus indicating possible environmental exposure, where geological and environmental investigations need to be carried out.}, } @article {pmid27699035, year = {2016}, author = {Pu, X and Dou, Y and Liu, D and Lu, S and Quan, S and Zhang, X and Ma, S and Zhao, Z}, title = {Membranous nephropathy associated with malignant pleural mesothelioma in an adult patient: A case report.}, journal = {Molecular and clinical oncology}, volume = {5}, number = {4}, pages = {407-410}, pmid = {27699035}, issn = {2049-9450}, abstract = {A 23-year-old man presented to our hospital with membranous nephropathy and received a detailed examination, including pleural biopsy, due to a feeling of chest oppression. The result of the pleural biopsy was malignant pleural mesothelioma. However, the patient did not have a history of asbestos or tobacco exposure. A review of the English literature identified only 7 reported cases of concomitant malignant mesothelioma and nephrotic syndrome. Furthermore, among the 7 cases reviewed, 6 had a history of asbestos exposure, 1 had a history of prolonged tobacco exposure and in only 1 case the renal pathology results revealed the presence of membranous nephropathy.}, } @article {pmid27698933, year = {2016}, author = {Walter, RF and Vollbrecht, C and Werner, R and Mairinger, T and Schmeller, J and Flom, E and Wohlschlaeger, J and Barbetakis, N and Paliouras, D and Chatzinikolaou, F and Adamidis, V and Tsakiridis, K and Zarogoulidis, P and Trakada, G and Christoph, DC and Schmid, KW and Mairinger, FD}, title = {Screening of Pleural Mesotheliomas for DNA-damage Repair Players by Digital Gene Expression Analysis Can Enhance Clinical Management of Patients Receiving Platin-Based Chemotherapy.}, journal = {Journal of Cancer}, volume = {7}, number = {13}, pages = {1915-1925}, pmid = {27698933}, issn = {1837-9664}, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare, predominantly asbestos-related and biologically highly aggressive tumour leading to a dismal prognosis. Multimodality therapy consisting of platinum-based chemotherapy is the treatment of choice. The reasons for the rather poor efficacy of platinum compounds remain largely unknown.

MATERIAL AND METHODS: For this exploratory mRNA study, 24 FFPE tumour specimens were screened by digital gene expression analysis. Based on data from preliminary experiments and recent literature, a total of 366 mRNAs were investigated using a Custom CodeSet from NanoString. All statistical analyses were calculated with the R i386 statistical programming environment.

RESULTS: CDC25A and PARP1 gene expression were correlated with lymph node spread, BRCA1 and TP73 expression levels with higher IMIG stage. NTHL1 and XRCC3 expression was associated with TNM stage. CHECK1 as well as XRCC2 expression levels were correlated with tumour progression in the overall cohort of patients. CDKN2A and MLH1 gene expression influenced overall survival in this collective. In the adjuvant treated cohort only, CDKN2A, CHEK1 as well as ERCC1 were significantly associated with overall survival. Furthermore, TP73 expression was associated with progression in this subgroup.

CONCLUSION: DNA-damage response plays a crucial role in response to platin-based chemotherapeutic regimes. In particular, CHEK1, XRCC2 and TP73 are strongly associated with tumour progression. ERCC1, MLH1, CDKN2A and most promising CHEK1 are prognostic markers for OS in MPM. TP73, CDKN2A, CHEK1 and ERCC1 seem to be also predictive markers in adjuvant treated MPMs. After a prospective validation, these markers may improve clinical and pathological practice, finally leading to a patients' benefit by an enhanced clinical management.}, } @article {pmid27696225, year = {2016}, author = {Valenzuela, M and Giraldo, M and Gallo-Murcia, S and Pineda, J and Santos, L and Ramos-Bonilla, JP}, title = {Recent Scientific Evidence Regarding Asbestos Use and Health Consequences of Asbestos Exposure.}, journal = {Current environmental health reports}, volume = {3}, number = {4}, pages = {335-347}, pmid = {27696225}, issn = {2196-5412}, mesh = {Asbestos, Serpentine/*adverse effects ; Asbestosis ; Carcinogens/toxicity ; Environmental Exposure/adverse effects ; Humans ; Mesothelioma/*epidemiology ; Occupational Diseases/chemically induced ; Occupational Exposure/*adverse effects ; }, abstract = {To justify the continuous use of two million tons of asbestos every year, it has been argued that a safe/controlled use can be achieved. The aim of this review was to identify recent scientific studies that present empirical evidence of: 1) health consequences resulting from past asbestos exposures and 2) current asbestos exposures resulting from asbestos use. Articles with evidence that could support or reject the safe/controlled use argument were also identified. A total of 155 articles were included in the review, and 87 % showed adverse asbestos health consequences or high asbestos exposures. Regarding the safe/controlled use, 44 articles were identified, and 82 % had evidence suggesting that the safe/controlled use is not being achieved. A large percentage of articles with evidence that support the safe/controlled use argument have a conflict of interest declared. Most of the evidence was developed in high-income countries and in countries that have already banned asbestos.}, } @article {pmid27687963, year = {2016}, author = {Nowak, AK and Chansky, K and Rice, DC and Pass, HI and Kindler, HL and Shemanski, L and Billé, A and Rintoul, RC and Batirel, HF and Thomas, CF and Friedberg, J and Cedres, S and de Perrot, M and Rusch, VW and , }, title = {The IASLC Mesothelioma Staging Project: Proposals for Revisions of the T Descriptors in the Forthcoming Eighth Edition of the TNM Classification for Pleural Mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {11}, number = {12}, pages = {2089-2099}, doi = {10.1016/j.jtho.2016.08.147}, pmid = {27687963}, issn = {1556-1380}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Lung Neoplasms/*classification/pathology ; Mesothelioma/*classification/pathology ; Mesothelioma, Malignant ; Neoplasm Staging/*classification ; Pleural Neoplasms/*classification/pathology ; }, abstract = {INTRODUCTION: The current T component for malignant pleural mesothelioma (MPM) has been predominantly informed by surgical data sets and consensus. The International Association for the Study of Lung Cancer undertook revision of the seventh edition of the staging system for MPM with the goal of developing recommendations for the eighth edition.

METHODS: Data elements including detailed T descriptors were developed by consensus. Tumor thickness at three pleural levels was also recorded. An electronic data capture system was established to facilitate data submission.

RESULTS: A total of 3519 cases were submitted to the database. Of those eligible for T-component analysis, 509 cases had only clinical staging, 836 cases had only surgical staging, and 642 cases had both available. Survival was examined for T categories according to the current seventh edition staging system. There was clear separation between all clinically staged categories except T1a versus T1b (hazard ratio = 0.99, p = 0.95) and T3 versus T4 (hazard ratio = 1.22, p = 0.09), although the numbers of T4 cases were small. Pathological staging failed to demonstrate a survival difference between adjacent categories with the exception of T3 versus T4. Performance improved with collapse of T1a and T1b into a single T1 category; no current descriptors were shifted or eliminated. Tumor thickness and nodular or rindlike morphology were significantly associated with survival.

CONCLUSIONS: A recommendation to collapse both clinical and pathological T1a and T1b into a T1 classification will be made for the eighth edition staging system. Simple measurement of pleural thickness has prognostic significance and should be examined further with a view to incorporation into future staging.}, } @article {pmid27687962, year = {2016}, author = {Rusch, VW and Chansky, K and Kindler, HL and Nowak, AK and Pass, HI and Rice, DC and Shemanski, L and Galateau-Sallé, F and McCaughan, BC and Nakano, T and Ruffini, E and van Meerbeeck, JP and Yoshimura, M and , }, title = {The IASLC Mesothelioma Staging Project: Proposals for the M Descriptors and for Revision of the TNM Stage Groupings in the Forthcoming (Eighth) Edition of the TNM Classification for Mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {11}, number = {12}, pages = {2112-2119}, doi = {10.1016/j.jtho.2016.09.124}, pmid = {27687962}, issn = {1556-1380}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Lung Neoplasms/*classification/pathology ; Mesothelioma/*classification/pathology ; Mesothelioma, Malignant ; Neoplasm Staging/*classification ; Pleural Neoplasms/*classification/pathology ; }, abstract = {INTRODUCTION: The M component and TNM stage groupings for malignant pleural mesothelioma (MPM) have been empirical. The International Association for the Study of Lung Cancer developed a multinational database to propose evidence-based revisions for the eighth edition of the TNM classification of MPM.

METHODS: Data from 29 centers were submitted either electronically or by transfer of existing institutional databases. The M component as it currently stands was validated by confirming sufficient discrimination (by Kaplan-Meier analysis) with respect to overall survival (OS) between the clinical M0 (cM0) and cM1 categories. Candidate stage groups were developed by using a recursive partitioning and amalgamation algorithm applied to all cM0 cases.

RESULTS: Of 3519 submitted cases, 2414 were analyzable and 84 were cM1 cases. Median OS for cM1 cases was 9.7 months versus 13.4 months (p = 0.0013) for the locally advanced (T4 or N3) cM0 cases, supporting inclusion of only cM1 in the stage IV group. Exploratory analyses suggest a possible difference in OS for single- versus multiple-site cM1 cases. A recursive partitioning and amalgamation-generated survival tree on the OS outcomes restricted to cM0 cases with the newly proposed (eighth edition) T and N components indicates that optimal stage groupings for the eighth edition will be as follows: stage IA (T1N0), stage IB (T2-3N0), stage II (T1-2N1), stage IIIA (T3N1), stage IIIB (T1-3N2 or any T4), and stage IV (any M1).

CONCLUSIONS: This first evidence-based revision of the TNM classification for MPM leads to substantial changes in the T and N components and the stage groupings.}, } @article {pmid27681566, year = {2016}, author = {Mensi, C and De Matteis, S and Catelan, D and Dallari, B and Riboldi, L and Pesatori, AC and Consonni, D}, title = {Geographical patterns of mesothelioma incidence and asbestos exposure in Lombardy, Italy.}, journal = {La Medicina del lavoro}, volume = {107}, number = {5}, pages = {340-355}, pmid = {27681566}, issn = {0025-7818}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Female ; Humans ; Incidence ; Italy/epidemiology ; Lung Neoplasms/*epidemiology/*etiology ; Male ; Mesothelioma/*epidemiology/*etiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/*adverse effects ; Young Adult ; }, abstract = {BACKGROUND: Measuring malignant mesothelioma (MM) occurrence is a useful means to monitor the impact of past asbestos exposure and possibly identify new sources of asbestos exposure.

OBJECTIVES: Aim of this study is to describe the results of the MM registry of the Lombardy Region, North-West Italy, the most populated (currently, 10 million inhabitants) and industrialised Italian region.

METHODS: We extracted from the Lombardy Region Mesothelioma Registry (Registro Mesoteliomi Lombardia, RML) database all incident cases of MM (pleura, peritoneum, pericardium, and tunica vaginalis testis) with first diagnosis in 2000 through 2012. For each Province, we calculated crude and standardised incidence rates using Italy 2001, European, and world (Segi's) standard populations. To examine spatial patterns of MM occurrence across municipalities we drew maps of crude rates smoothed according to the Besag, York and Mollié (BYM) method.

RESULTS: We recorded 4442 MM cases (2850 in men and 1592 in women), representing about one fourth of MM cases occurring in Italy. Occupational exposure was more frequent in men (73.6%) than in women (38.2%). The crude regional rates were 4.7 per 100,000 person-years in men and 2.5 per 100,000 person-years in women. The highest rates were observed in the Pavia Province (crude rates: 8.7 per 100,000 in men and 5.3 and per 100,000 person-years in women).

CONCLUSIONS: This study documented high MM occurrence in both genders, attributable to extensive asbestos exposure in the past.}, } @article {pmid27669062, year = {2016}, author = {Lamote, K and Vynck, M and Van Cleemput, J and Thas, O and Nackaerts, K and van Meerbeeck, JP}, title = {Detection of malignant pleural mesothelioma in exhaled breath by multicapillary column/ion mobility spectrometry (MCC/IMS).}, journal = {Journal of breath research}, volume = {10}, number = {4}, pages = {046001}, doi = {10.1088/1752-7155/10/4/046001}, pmid = {27669062}, issn = {1752-7163}, mesh = {Adult ; Aged ; Breath Tests/*methods ; *Exhalation ; Female ; Humans ; Lung Neoplasms/*diagnosis ; Male ; Mass Spectrometry/*methods ; Mesothelioma/*diagnosis ; Mesothelioma, Malignant ; Middle Aged ; Models, Biological ; Pleural Neoplasms/*diagnosis ; ROC Curve ; Statistics as Topic ; Volatile Organic Compounds/analysis ; }, abstract = {Malignant pleural mesothelioma (MPM) is predominantly caused by previous asbestos exposure. Diagnosis often happens in advanced stages restricting any therapeutic perspectives. Early stage detection via breath analysis was explored using multicapillary column/ion mobility spectrometry (MCC/IMS) to detect volatile organic compounds (VOCs) in the exhaled breath of MPM patients in comparison to former occupational asbestos-exposed and non-exposed controls. Breath and background samples of 23 MPM patients, 22 asymptomatic former asbestos (AEx) workers and 21 healthy non-asbestos exposed persons were taken for analysis. After background correction, we performed a logistic least absolute shrinkage and selection operator (lasso) regression to select the most important VOCs, followed by receiver operating characteristic (ROC) analysis. MPM patients were discriminated from both controls with 87% sensitivity, 70% specificity and respective positive and negative predictive values of 61% and 91%. The overall accuracy was 76% and the area under the ROC-curve was 0.81. AEx individuals could be discriminated from MPM patients with 87% sensitivity, 86% specificity and respective positive and negative predictive values of 87% and 86%. The overall accuracy was 87% with an area under the ROC-curve of 0.86. Breath analysis by MCC/IMS allows MPM patients to be discriminated from controls and holds promise for further investigation as a screening tool for former asbestos-exposed persons at risk of developing MPM.}, } @article {pmid27660729, year = {2016}, author = {Gleason, JB and Tashtoush, B and Diacovo, MJ}, title = {Biphasic Malignant Pleural Mesothelioma Masquerading as a Primary Skeletal Tumor.}, journal = {Case reports in pulmonology}, volume = {2016}, number = {}, pages = {7560929}, pmid = {27660729}, issn = {2090-6846}, abstract = {Biphasic malignant pleural mesothelioma is a rare malignant tumor, usually presenting as a pleural-based mass in a patient with history of chronic asbestos exposure. We herein report a case of a 41-year-old man who presented with chest pain and had a chest computed tomography (CT) scan suggestive of a primary skeletal tumor originating from the ribs (chondrosarcoma or osteosarcoma), with no history of asbestos exposure. CT-guided core needle biopsies were diagnosed as malignant sarcomatoid mesothelioma. Surgical resection and chest wall reconstruction were performed, confirming the diagnosis and revealing a secondary histologic component (epithelioid), supporting the diagnosis of biphasic malignant mesothelioma.}, } @article {pmid27650313, year = {2016}, author = {Sayan, M and Mossman, BT}, title = {The NLRP3 inflammasome in pathogenic particle and fibre-associated lung inflammation and diseases.}, journal = {Particle and fibre toxicology}, volume = {13}, number = {1}, pages = {51}, pmid = {27650313}, issn = {1743-8977}, support = {P01 HL067004/HL/NHLBI NIH HHS/United States ; T32 ES007122/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Humans ; Inflammasomes/*metabolism ; Lung Diseases/*chemically induced ; NLR Family, Pyrin Domain-Containing 3 Protein/*metabolism ; Particulate Matter/toxicity ; Pneumonia/*chemically induced ; Silicon Dioxide/toxicity ; }, abstract = {The concept of the inflammasome, a macromolecular complex sensing cell stress or danger signals and initiating inflammation, was first introduced approximately a decade ago. Priming and activation of these intracellular protein platforms trigger the maturation of pro-inflammatory chemokines and cytokines, most notably, interleukin-1β (IL-1β) and IL-18, to promulgate innate immune defenses. Although classically studied in models of gout, Type II diabetes, Alzheimer's disease, and multiple sclerosis, the importance and mechanisms of action of inflammasome priming and activation have recently been elucidated in cells of the respiratory tract where they modulate the responses to a number of inhaled pathogenic particles and fibres. Most notably, inflammasome activation appears to regulate the balance between tissue repair and inflammation after inhalation of pathogenic pollutants such as asbestos, crystalline silica (CS), and airborne particulate matter (PM). Different types of fibres and particles may have distinct mechanisms of inflammasome interaction and outcome. This review summarizes the structure and function of inflammasomes, the interplay between various chemokines and cytokines and cell types of the lung and pleura after inflammasome activation, and the events leading to the development of non-malignant (allergic airway disease and chronic obstructive pulmonary disease (COPD), asbestosis, silicosis) and malignant (mesothelioma, lung cancer) diseases by pathogenic particulates. In addition, it emphasizes the importance of communication between cells of the immune system, target cells of these diseases, and components of the extracellular matrix (ECM) in regulation of inflammasome-mediated events.}, } @article {pmid27644679, year = {2016}, author = {Kattan, J and Eid, R and Kourie, HR and Farhat, F and Ghosn, M and Ghorra, C and Tomb, R}, title = {Mesotheliomas in Lebanon: Witnessing a Change in Epidemiology.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {17}, number = {8}, pages = {4169-4173}, pmid = {27644679}, issn = {2476-762X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Female ; Humans ; Incidence ; Lebanon/epidemiology ; Lung Neoplasms/*epidemiology/*pathology ; Male ; Mesothelioma/*epidemiology/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/adverse effects ; Peritoneal Neoplasms/epidemiology/pathology ; Peritoneum/pathology ; Pleura/pathology ; Pleural Neoplasms/epidemiology/pathology ; Retrospective Studies ; }, abstract = {BACKGROUND: Mesotheliomas are relatively rare tumors in Lebanon. The only previous study goes back to 14 years ago, when we published epidemiological characteristics of mesotheliomas in Lebanon, showing that the pleural location accounted for the vast majority of cases, with clear evidence of asbestos exposure from the Eternit factory of Chekka region. The objective of this current study was to estimate the incidence of mesothelioma in the past decade and to identify its epidemiological, clinical and therapeutic characteristics, making comparisons with our first study published in 2001.

MATERIALS AND METHODS: Between 2002 and 2014, patients diagnosed with malignant mesothelioma at Hotel-Dieu de France University Hospital were investigated. Epidemiological data focusing on asbestos exposure history were collected from medical records and interviews with the families.

RESULTS: A total of 26 patients were diagnosed with mesothelioma, 21 of which were successfully investigated. The mean age of these 21 patients is 62.5 (19-82). Only 3 (14.29%) are women. 18 (85.71%) were smokers. Among the 21 available mesotheliomas, 15 (71.4%) are pleural, while 5 (23.8%) are peritoneal and 1 (4.8%) pericardial. Only 60% of patients with pleural mesothelioma and 50% of those with an obvious exposure to asbestos lived and/or worked in Chekka region. The mean time of asbestos exposure in patients with mesothelioma is 24.5 (1-50) years and the mean latency is 37.4 (4-61) years. Of the 21 patients, 10 (47.6%) underwent surgery during their treatment, 16 (76.2%) received chemotherapy and 3 (14.3%) received best supportive care.

CONCLUSIONS: Compared to the previous study (1991-2000), substantial changes in the epidemiology of mesothelioma in Lebanon were observed, such as an increase in peritoneal localizations and a lower correlation with Chekka region asbestos contamination.}, } @article {pmid27628605, year = {2016}, author = {Kanai, G and Kakuta, T and Hirukawa, T and Okamatsu, C and Fukagawa, M}, title = {A Case of Encapsulating Peritoneal Sclerosis Complicated by Malignant Peritoneal Mesothelioma.}, journal = {The Tokai journal of experimental and clinical medicine}, volume = {41}, number = {3}, pages = {135-138}, pmid = {27628605}, issn = {2185-2243}, mesh = {Biopsy ; Female ; Humans ; Kidney Failure, Chronic/complications/therapy ; Lung Neoplasms/*complications/*diagnosis/pathology ; Mesothelioma/*complications/*diagnosis/pathology ; Mesothelioma, Malignant ; Middle Aged ; Peritoneal Dialysis ; Peritoneal Fibrosis/*diagnosis/*etiology ; Peritoneal Neoplasms/*complications/*diagnosis/pathology ; Tomography, X-Ray Computed ; }, abstract = {We report a case of peritoneal mesothelioma discovered in a patient during peritoneal dialysis. The patient was a 55-year-old woman who had no history of asbestos exposure. Owing to end-stage kidney failure, she had been undergoing peritoneal dialysis for over 8 years, and she had been diagnosed with encapsulating peritoneal sclerosis. She was admitted to the hospital for intestinal obstruction. Three months later, she noticed an enlarging mass in the epigastric region. Computed tomography showed a 10-cm mass originating in the abdominal wall that had invaded the liver. It was diagnosed as malignant mesothelioma via biopsy. Cases of sarcoma-like mass-forming peritoneal mesothelioma are rare, and there are no prior reports of encapsulating peritoneal sclerosis complicated by malignant peritoneal mesothelioma. Thus, this unique case of peritoneal mesothelioma can provide us with important knowledge about this rare entity.}, } @article {pmid27623107, year = {2016}, author = {Kanteti, R and Riehm, JJ and Dhanasingh, I and Lennon, FE and Mirzapoiazova, T and Mambetsariev, B and Kindler, HL and Salgia, R}, title = {PI3 Kinase Pathway and MET Inhibition is Efficacious in Malignant Pleural Mesothelioma.}, journal = {Scientific reports}, volume = {6}, number = {}, pages = {32992}, pmid = {27623107}, issn = {2045-2322}, mesh = {Aminopyridines/administration & dosage/pharmacology ; Animals ; Antineoplastic Agents/administration & dosage/*pharmacology ; Apoptosis/drug effects ; Bridged Bicyclo Compounds, Heterocyclic/pharmacology ; Cell Cycle Checkpoints/drug effects ; Cell Line, Tumor ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Crizotinib ; Drug Synergism ; Female ; Humans ; Lung Neoplasms/*drug therapy/*metabolism/pathology ; Mesothelioma/*drug therapy/*metabolism/pathology ; Mesothelioma, Malignant ; Mice ; Mice, Nude ; Microtubules/drug effects ; Morpholines/administration & dosage/pharmacology ; *Phosphoinositide-3 Kinase Inhibitors ; Pleural Neoplasms/*drug therapy/*metabolism/pathology ; Protein Kinase Inhibitors/pharmacology ; Proto-Oncogene Proteins c-met/*antagonists & inhibitors ; Pyrazoles/administration & dosage/pharmacology ; Pyridines/administration & dosage/pharmacology ; Pyrimidines/pharmacology ; Signal Transduction/drug effects ; Xenograft Model Antitumor Assays ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive cancer that is commonly associated with prior asbestos exposure. Receptor tyrosine kinases (RTKs) such as MET and its downstream target PI3K are overexpressed and activated in a majority of MPMs. Here, we studied the combinatorial therapeutic efficacy of the MET/ALK inhibitor crizotinib, with either a pan-class I PI3K inhibitor, BKM120, or with a PI3K/mTOR dual inhibitor, GDC-0980, in mesothelioma. Cell viability results showed that MPM cells were highly sensitive to crizotinib, BKM120 and GDC-0980 when used individually and their combination was more effective in suppressing growth. Treatment of MPM cells with these inhibitors also significantly decreased cell migration, and the combination of them was synergistic. Treatment with BKM120 alone or in combination with crizotinib induced G2-M arrest and apoptosis. Both crizotinib and BKM120 strongly inhibited the activity of MET and PI3K as evidenced by the decreased phosphorylation of MET, AKT and ribosomal S6 kinase. Using a PDX mouse model, we showed that a combination of crizotinib with BKM120 was highly synergetic in inhibiting MPM tumor growth. In conclusion our findings suggest that dual inhibition of PI3K and MET pathway is an effective strategy in treating MPM as compared to a single agent.}, } @article {pmid27621868, year = {2016}, author = {Sandri, A and Guerrera, F and Roffinella, M and Olivetti, S and Costardi, L and Oliaro, A and Filosso, PL and Lausi, PO and Ruffini, E}, title = {Validation of EORTC and CALGB prognostic models in surgical patients submitted to diagnostic, palliative or curative surgery for malignant pleural mesothelioma.}, journal = {Journal of thoracic disease}, volume = {8}, number = {8}, pages = {2121-2127}, pmid = {27621868}, issn = {2072-1439}, abstract = {BACKGROUND: To assess the trend of our surgical patients affected by malignant pleural mesothelioma (MPM) and submitted to diagnostic/palliative or curative surgical procedures and to validate the European Organisation for Research and Treatment of Cancer (EORTC) prognostic score in our patient population.

METHODS: This is a cohort study of patients submitted to surgery for MPM from January 2007 to December 2013. Primary outcome was overall survival (OS). Univariate and multivariate-adjusted comparisons by EORTC prognostic score for OS were accomplished using Cox method. Adjusted models included the following clinical variables: kind of procedure, smoking habit, asbestos exposure, Charlson's Comorbidity Index (CCI), clinical tumor stage, adjuvant chemotherapy, dyspnoea, chest pain and haematological variables according to the score features. Nomenclature of the surgical procedures matches the International Association for the Study Lung Cancer (IASLC)/International Mesothelioma Interest Group (iMIG).

RESULTS: One-hundred sixty-six consecutive cases were collected: the median age at surgery was 73 years and 123 patients (75%) had a history of asbestos exposure. Ninty patients (54%) were submitted to a palliative/diagnostic thoracoscopy, 30 to pleurectomy/decortication (P/D), and 6 to extra-pleural pneumonectomy (EPP). Clinical TNM stages were as follows: 99 (60%) stage I-II, 34 (20%) stage III and 33 (20%) stage IV. The median follow-up (FU) was 19 months [interquartile range (IQR), 9-31 months] and the FU-completeness was 98%. By the end of the study 130 patients died (78%). One- and 3-year OS was 60% and 36%, respectively. Patients submitted to EPP and P/D showed a better survival (P=0.013). Multivariable model showed an independent prognostic value of EORTC score (HR =2.86, P<0.001).

CONCLUSIONS: In selected patients, aggressive surgical approaches, although not radical, may still be beneficial. The EORTC prognostic index proved to be an independent prognostic factor in our cohort of patients and therefore is a reliable and valid instrument that may be implemented in the daily practice.}, } @article {pmid27619223, year = {2016}, author = {Geltner, C and Errhalt, P and Baumgartner, B and Ambrosch, G and Machan, B and Eckmayr, J and Klikovits, T and Hoda, MA and Popper, H and Klepetko, W and , }, title = {Management of malignant pleural mesothelioma - part 1: epidemiology, diagnosis, and staging : Consensus of the Austrian Mesothelioma Interest Group (AMIG).}, journal = {Wiener klinische Wochenschrift}, volume = {128}, number = {17-18}, pages = {611-617}, pmid = {27619223}, issn = {1613-7671}, mesh = {Diagnosis, Differential ; Diagnostic Imaging/standards ; Evidence-Based Medicine/standards ; Humans ; Medical Oncology/standards ; Mesothelioma/*diagnosis/*epidemiology/pathology ; Neoplasm Staging ; Pleural Effusion, Malignant/*diagnosis/*epidemiology/pathology ; Pleural Neoplasms/*diagnosis/*epidemiology/pathology ; Practice Guidelines as Topic ; Prevalence ; Risk Factors ; }, abstract = {Malignant pleural mesothelioma is a rare malignant disease that in the majority of cases is associated with asbestos exposure. The incidence in Europe is about 20 per million inhabitants and it is increasing worldwide. Initial symptoms are shortness of breath, pleural effusion, cough, and chest pain. The typical growth pattern is along the pleural surface; however, infiltration of the lung and/or mediastinal and chest wall structures can occur in a more advanced stage. Ultimately, distant metastases outside the chest can result. Several histological subtypes of pleural mesothelioma exist, which must be differentiated from either benign diseases or metastases in the pleural space by other tumor entities. This differential diagnosis can be very difficult and a large panel of immunohistochemical markers is required to establish the exact diagnosis. The standard procedure for confirming the disease and obtaining sufficient tissue for the diagnosis is videothoracoscopy. Full thickness biopsies are required, while transthoracic needle puncture of pleural fluid or tissue is considered to be insufficient for a cytological diagnosis. Complete and detailed staging is mandatory for categorization of the disease as well as for therapeutic decision making.}, } @article {pmid27612329, year = {2016}, author = {Biancosino, C and Redwan, B and Krüger, M and Eberlein, M and Bölükbas, S}, title = {[Malignant Pleural Mesotheliomas].}, journal = {Zentralblatt fur Chirurgie}, volume = {141 Suppl 1}, number = {}, pages = {S61-73}, doi = {10.1055/s-0042-110248}, pmid = {27612329}, issn = {1438-9592}, mesh = {Biomarkers, Tumor/analysis ; Combined Modality Therapy ; Diagnosis, Differential ; Diagnostic Imaging ; Follow-Up Studies ; Humans ; Mesothelioma/diagnosis/pathology/*therapy ; Paraneoplastic Syndromes/diagnosis/pathology/therapy ; Pleural Neoplasms/diagnosis/pathology/*therapy ; }, abstract = {Malignant pleural mesotheliomas (MPM) are very aggressive tumors, which originate from the mesothelial cells of the pleural surface. The main risk factor associated with MPM is exposure to asbestos. The latency period between asbestos exposure and MPM can be 30-60 years. Clinical symptoms and signs are often nonspecifc. The diagnosis of MPM requires an adequate tissue specimen for pathological examination, and video assisted thoracoscopic surgey (VATS) is associated with the highest diagnostic yield. MPM are histologically classified into epitheloid, sacromatoid and biphasic (mixed) sub-types. Accurate staging with invasive tests, if needed, is an important step before an interdisciplinary team can decide on an optimal (multi-modal) treatment approach. A multi-modal treatment approach (surgery, radiation oncology and chemotherapy) is superior to all approaches relying only on a single modality, if the patient qualifies for it from an oncological and functional standpoint. The goal of the surgical therapy is to achieve macroscopic complete resection. There are two competing surgical approaches and philosophies: extrapleural pneumonectomy (EPP) and radical pleurectomy (RP). Over the last years a paradigm shift from EPP to RP occurred and RP is now often the preferred surgical option.}, } @article {pmid27605433, year = {2016}, author = {Greening, DW and Ji, H and Chen, M and Robinson, BW and Dick, IM and Creaney, J and Simpson, RJ}, title = {Secreted primary human malignant mesothelioma exosome signature reflects oncogenic cargo.}, journal = {Scientific reports}, volume = {6}, number = {}, pages = {32643}, pmid = {27605433}, issn = {2045-2322}, mesh = {Cell Communication/genetics ; Cell Line, Tumor ; Exosomes/*genetics/pathology ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Lung Neoplasms/*genetics/pathology ; Mesothelioma/*genetics/pathology ; Mesothelioma, Malignant ; Neoplasm Proteins/*genetics ; *Proteomics ; Tumor Microenvironment/genetics ; }, abstract = {Malignant mesothelioma (MM) is a highly-aggressive heterogeneous malignancy, typically diagnosed at advanced stage. An important area of mesothelioma biology and progression is understanding intercellular communication and the contribution of the secretome. Exosomes are secreted extracellular vesicles shown to shuttle cellular cargo and direct intercellular communication in the tumour microenvironment, facilitate immunoregulation and metastasis. In this study, quantitative proteomics was used to investigate MM-derived exosomes from distinct human models and identify select cargo protein networks associated with angiogenesis, metastasis, and immunoregulation. Utilising bioinformatics pathway/network analyses, and correlation with previous studies on tumour exosomes, we defined a select mesothelioma exosomal signature (mEXOS, 570 proteins) enriched in tumour antigens and various cancer-specific signalling (HPGD/ENO1/OSMR) and secreted modulators (FN1/ITLN1/MAMDC2/PDGFD/GBP1). Notably, such circulating cargo offers unique insights into mesothelioma progression and tumour microenvironment reprogramming. Functionally, we demonstrate that oncogenic exosomes facilitate the migratory capacity of fibroblast/endothelial cells, supporting the systematic model of MM progression associated with vascular remodelling and angiogenesis. We provide biophysical and proteomic characterisation of exosomes, define a unique oncogenic signature (mEXOS), and demonstrate the regulatory capacity of exosomes in cell migration/tube formation assays. These findings contribute to understanding tumour-stromal crosstalk in the context of MM, and potential new diagnostic and therapeutic extracellular targets.}, } @article {pmid27602956, year = {2016}, author = {Wang, S and Jiang, L and Han, Y and Chew, SH and Ohara, Y and Akatsuka, S and Weng, L and Kawaguchi, K and Fukui, T and Sekido, Y and Yokoi, K and Toyokuni, S}, title = {Urokinase-type plasminogen activator receptor promotes proliferation and invasion with reduced cisplatin sensitivity in malignant mesothelioma.}, journal = {Oncotarget}, volume = {7}, number = {43}, pages = {69565-69578}, pmid = {27602956}, issn = {1949-2553}, mesh = {Animals ; Antineoplastic Agents/pharmacology ; Apoptosis/drug effects/genetics ; Asbestos ; Cell Line, Tumor ; Cell Proliferation/*drug effects/genetics ; Cisplatin/*pharmacology ; Gene Expression Profiling/methods ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/chemically induced/*genetics/metabolism ; Mesothelioma/chemically induced/*genetics/metabolism ; Mesothelioma, Malignant ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Invasiveness ; RNA Interference ; Rats ; Receptors, Urokinase Plasminogen Activator/blood/*genetics/metabolism ; Transplantation, Heterologous ; }, abstract = {Malignant mesothelioma (MM) is a rare neoplasm associated with asbestos exposure. The prognosis of MM is poor because it is aggressive and highly resistant to chemotherapy. Using a rat model of asbestos-induced MM, we found elevated urokinase-type plasminogen activator receptor (uPAR; Plaur) expression in rat tissues, which was associated with poor prognosis. The proliferation, migration and invasion of MM cells were suppressed by uPAR knockdown and increased by overexpression experiments, irrespective of urokinase-type plasminogen activator (uPA; Plau) levels. More importantly, we found that uPAR expression is associated with sensitivity to cisplatin in MM through the PI3K/AKT pathway, which was demonstrated with specific inhibitors, LY294002 and Akti-1/2. uPAR knockdown significantly increased sensitivity to cisplatin whereas its overexpression significantly decreased cisplatin sensitivity. Furthermore, sera and tissues from MM patients showed significantly high uPAR levels, which suggested the pathogenic role of uPAR in the tumor biology of human MM. In conclusion, our findings indicate that uPAR levels are associated with malignant characteristics and cisplatin sensitivity of MM. In addition to the potential use of uPAR as a prognostic marker, the combination of uPAR abrogation and cisplatin may reveal a promising therapeutic approach for MM.}, } @article {pmid27599565, year = {2016}, author = {Hashimoto, K and Okuma, Y and Hosomi, Y and Hishima, T}, title = {Malignant mesothelioma of the pleura with desmoplastic histology: a case series and literature review.}, journal = {BMC cancer}, volume = {16}, number = {1}, pages = {718}, pmid = {27599565}, issn = {1471-2407}, mesh = {Aged ; Female ; Humans ; Lung Neoplasms/*pathology/therapy ; Male ; Mesothelioma/*pathology/therapy ; Mesothelioma, Malignant ; Middle Aged ; Neoplasm Staging ; Pleural Neoplasms/*pathology/therapy ; Prognosis ; Retrospective Studies ; }, abstract = {BACKGROUND: Desmoplastic malignant pleural mesothelioma (DMM) is rare histological subtype of diffuse malignant pleural mesothelioma (MPM), accounting for 5-10 % of cases. It has a poor prognosis, with direct invasion of the chest wall or lungs and distant metastases. Its pathological characteristics include dense collagen fibers in a storiform pattern. Its pretreatment pathological diagnosis is difficult, with fibrous pleuritis and reactive mesothelial hyperplasia as potential differential diagnoses.

CASE PRESENTATION: We retrospectively reviewed the medical charts of patients with MPM from 1996 to 2012. Among 60 patients with MPM, four patients with the desmoplastic subtype were identified and their clinical characteristics, including asbestos exposure, treatment, and prognosis, were reviewed. All of the patients with DMM were men, with a median age of 69 years (range: 63-74 years). All four patients had been exposed to asbestos. The definitive diagnosis was made histologically and the International Mesothelioma Interest Group classification was advanced (III/IV: 2/3) in all four patients. Three patients were treated with chemotherapy (two with cisplatin/pemetrexed and one with cisplatin/gemcitabine) and one patient underwent surgery. The median survival time in the patients with DMM was 3.8 months (range: 0.9-11.5 months), compared with 10.5 months in patients with other subtypes of MPM in our institution.

CONCLUSIONS: DMM continues to have a poor prognosis. It is important to recognize this variant and distinguish it from pleural plaques, non-specific reactive pleural fibrosis, pleurisy, and other lung diseases.}, } @article {pmid27587956, year = {2016}, author = {Cha, YK and Kim, JS and Kim, Y and Kim, YK}, title = {Radiologic Diagnosis of Asbestosis in Korea.}, journal = {Korean journal of radiology}, volume = {17}, number = {5}, pages = {674-683}, pmid = {27587956}, issn = {2005-8330}, mesh = {Asbestos/adverse effects ; Asbestosis/*diagnostic imaging/etiology ; Diagnosis, Differential ; Humans ; Idiopathic Pulmonary Fibrosis/diagnosis ; Lung/diagnostic imaging ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Occupational Exposure/adverse effects ; Radiography ; Tomography, X-Ray Computed ; }, abstract = {Asbestosis is the most important change noted in the lung parenchyma after environmental and occupational exposure to asbestos fibers. It is characterized by diffuse interstitial pulmonary fibrosis. In Korea, the incidence of asbestosis will continue to increase for many years to come and the government enacted the Asbestos Damage Relief Law in 2011 to provide compensation to those suffering from asbestos-related diseases. Radiologic evaluation is necessary for diagnosis of asbestosis, and radiologists play a key role in this process. Therefore, it is important for radiologists to be aware of the various imaging features of asbestosis.}, } @article {pmid29903130, year = {2016}, author = {Jia, X and Mi, J and Yang, L and Wei, B and Cao, S and Hu, L and Lu, R}, title = {[A case-control study on the relationship between food preference and lung cancer and mesothelioma in a rural area with naturally occurring asbestos].}, journal = {Wei sheng yan jiu = Journal of hygiene research}, volume = {45}, number = {5}, pages = {771-776}, pmid = {29903130}, issn = {1000-8020}, mesh = {Asbestos/*toxicity ; Case-Control Studies ; China/epidemiology ; Female ; *Food Preferences ; Humans ; Lung Neoplasms/ethnology/*etiology ; Male ; Mesothelioma/ethnology/*etiology ; Occupational Diseases/*etiology ; Occupational Exposure/*adverse effects ; }, abstract = {OBJECTIVE: To understand the relationship between food preference and lung cancer or malignant pleural mesothelioma and the interactive effect between food preference and asbestos exposure in a rural area with naturally occurring asbestos.

METHODS: At the basis of the cohort of Dayao in Yunnan, we performed a 1 ∶ 2 casecontrol study including 53 cases(23 cases for lung cancer and 26 cases for mesothelioma)and 106 age-and sex-matched normal healthy controls. In order to study the protective effect of food preference and the interactive effect between food preference and asbestos exposure, conditional logistic regression was used to estimate adjusted odds ratios(OR)and their 95% confidence intervals(CI) in both unvaried and multivariate analyses.

RESULTS: Both green tea and wild mushroom were inversely associated with lung cancer ormalignant pleural mesothelioma, and the adjusted ORs were: 0. 88(95% CI 0. 66-0. 87) for green tea, 0. 85(95% CI 0. 23- 0. 95) for wild mushroom intake. Food preference to wild mushroom modified the associations of Crocidolite ' s contacting, Respectively, relative excess risk due to interaction(RERI), attributable proportion due to interaction(API), synergy index(S) were 0. 86, 0. 26 and 0. 61.

CONCLUSION: Both green tea and wild mushroom might serve as protective factors on lung cancer or malignant pleural mesothelioma.}, } @article {pmid27577310, year = {2016}, author = {Pearce, L}, title = {Charity support is making rewarding roles possible.}, journal = {Nursing standard (Royal College of Nursing (Great Britain) : 1987)}, volume = {31}, number = {1}, pages = {38-39}, doi = {10.7748/ns.31.1.38.s41}, pmid = {27577310}, issn = {2047-9018}, mesh = {*Charities ; Nurse's Role ; *Nursing Staff ; United Kingdom ; }, abstract = {Mesothelioma UK is one of many charities that provide money for specialist nursing posts. Currently, it funds 14 nurses, who are employed by trusts to support those with this rare form of asbestos-related cancer for 2 days each week.}, } @article {pmid27570625, year = {2016}, author = {Luanpitpong, S and Wang, L and Davidson, DC and Riedel, H and Rojanasakul, Y}, title = {Carcinogenic Potential of High Aspect Ratio Carbon Nanomaterials.}, journal = {Environmental science. Nano}, volume = {3}, number = {3}, pages = {483-493}, pmid = {27570625}, issn = {2051-8153}, support = {R01 EB018857/EB/NIBIB NIH HHS/United States ; R01 ES022968/ES/NIEHS NIH HHS/United States ; }, abstract = {Engineered nanomaterials, including high aspect ratio carbon nanomaterials, are often commercialized without a complete human risk assessment and safety evaluation. A health concern has been raised that high aspect ratio nanomaterials such as carbon nanotubes may cause unintended health consequences, such as asbestos-like lung cancer and mesothelioma, when chronically inhaled. Considering the widespread industrial and clinical applications and the increasing incidence of human exposure to nanomaterials, it is important to address the issue of nanomaterial carcinogenicity in a timely manner. This review summarizes recent advances in nanomaterial genotoxicity and carcinogenicity with a focus on high aspect ratio carbon nanotubes, and discusses current knowledge gaps and future research directions.}, } @article {pmid27549627, year = {2016}, author = {Huaux, F and d'Ursel de Bousies, V and Parent, MA and Orsi, M and Uwambayinema, F and Devosse, R and Ibouraadaten, S and Yakoub, Y and Panin, N and Palmai-Pallag, M and van der Bruggen, P and Bailly, C and Marega, R and Marbaix, E and Lison, D}, title = {Mesothelioma response to carbon nanotubes is associated with an early and selective accumulation of immunosuppressive monocytic cells.}, journal = {Particle and fibre toxicology}, volume = {13}, number = {1}, pages = {46}, pmid = {27549627}, issn = {1743-8977}, mesh = {Animals ; Carcinogens/*toxicity ; Heterografts ; Humans ; Male ; Mesothelioma/*chemically induced/immunology ; Mice ; Mice, Inbred C57BL ; Monocytes/*immunology ; Nanotubes, Carbon/*toxicity ; Rats ; Rats, Wistar ; }, abstract = {BACKGROUND: The asbestos-like toxicity of some engineered carbon nanotubes (CNT), notably their capacity to induce mesothelioma, is a serious cause of concern for public health. Here we show that carcinogenic CNT induce an early and sustained immunosuppressive response characterized by the accumulation of monocytic Myeloid Derived Suppressor Cells (M-MDSC) that counteract effective immune surveillance of tumor cells.

METHODS: Wistar rats and C57BL/6 mice were intraperitoneally injected with carcinogenic multi-walled Mitsui-7 CNT (CNT-7) or crocidolite asbestos. Peritoneal mesothelioma development and immune cell accumulation were assessed until 12 months. Leukocyte sub-populations were identified by recording expression of CD11b/c and His48 by flow cytometry. The immunosuppressive activity on T lymphocytes of purified peritoneal leukocytes was assessed in a co-culture assay with activated spleen cells.

RESULTS: We demonstrate that long and short mesotheliomagenic CNT-7 injected in the peritoneal cavity of rats induced, like asbestos, an early and selective accumulation of monocytic cells (CD11b/c(int) and His48(hi)) which possess the ability to suppress polyclonal activation of T lymphocytes and correspond to M-MDSC. Peritoneal M-MDSC persisted during the development of peritoneal mesothelioma in CNT-7-treated rats but were only transiently recruited after non-carcinogenic CNT (CNT-M, CNT-T) injection. Peritoneal M-MDSC did not accumulate in mice which are resistant to mesothelioma development.

CONCLUSIONS: Our data provide new insights into the initial pathogenic events induced by CNT, adding a new component to the adverse outcome pathway leading to mesothelioma development. The specificity of the M-MDSC response after carcinogenic CNT exposure highlights the interest of this response for detecting the ability of new nanomaterials to cause cancer.}, } @article {pmid27542398, year = {2016}, author = {Franklin, P and Alfonso, H and Reid, A and Olsen, N and Shilkin, KB and Brims, F and de Klerk, N and Musk, AW}, title = {Asbestos exposure and histological subtype of malignant mesothelioma.}, journal = {Occupational and environmental medicine}, volume = {73}, number = {11}, pages = {749-752}, doi = {10.1136/oemed-2016-103721}, pmid = {27542398}, issn = {1470-7926}, mesh = {Aged ; Asbestos ; Asbestos, Crocidolite/adverse effects ; Humans ; Logistic Models ; Lung Neoplasms/*chemically induced/*pathology ; Male ; Mesothelioma/*chemically induced/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Mining ; Occupational Diseases/chemically induced/pathology ; Occupational Exposure/*adverse effects ; Prognosis ; Registries ; Surveys and Questionnaires ; Western Australia ; }, abstract = {BACKGROUND: Malignant mesothelioma (MM) has distinct histological subtypes (epithelioid, sarcomatoid and biphasic) with variable behaviour and prognoses. It is well recognised that survival time varies with the histological subtype of MM. It is not known, however, if asbestos exposure characteristics (type of asbestos, degree of exposure) are associated with different histological subtypes.

AIM: To determine if the pathological MM subtype is associated with the type of asbestos or the attributes of asbestos exposure.

METHODS: Cases of MM for the period 1962 until 2012, their main histological subtype and their most significant source of asbestos exposure were collected from the Western Australian Mesothelioma Registry. Exposure characteristics included, degree of asbestos exposure (including total days exposed, years since first exposure and, for crocidolite only, calculated cumulative exposure), source of exposure (occupational or environmental), form of asbestos handled (raw or processed) and type of asbestos (crocidolite only or mixed fibres).

RESULTS: Patients with the biphasic subtype were more likely to have occupational exposure (OR 1.83, 1.12 to 2.85) and exposure to raw fibres (OR 1.58, 1.19 to 2.10). However, differences between subtypes in the proportions with these different exposure characteristics were small and unlikely to be biologically relevant. Other indicators of asbestos exposure were not associated with the histological subtype of mesothelioma.

CONCLUSIONS: There was no strong evidence of a consistent role of asbestos exposure indicators in determining the histological subtype of MM.}, } @article {pmid27540559, year = {2016}, author = {Salamatipour, A and Mohanty, SK and Pietrofesa, RA and Vann, DR and Christofidou-Solomidou, M and Willenbring, JK}, title = {Asbestos Fiber Preparation Methods Affect Fiber Toxicity.}, journal = {Environmental science & technology letters}, volume = {3}, number = {7}, pages = {270-274}, pmid = {27540559}, issn = {2328-8930}, support = {P30 ES013508/ES/NIEHS NIH HHS/United States ; P42 ES023720/ES/NIEHS NIH HHS/United States ; R03 CA180548/CA/NCI NIH HHS/United States ; }, abstract = {To measure the toxic potential of asbestos fibers-a known cause of asbestosis, lung cancer, and malignant mesothelioma-asbestos minerals are generally first ground down to small fibers, but it is unknown whether the grinding condition itself changes the fiber toxicity. To evaluate this, we ground chrysotile ore with or without water for 5-30 min and quantified asbestos-induced reactive oxygen species generation in elicited murine peritoneal macrophages as an indicator of fiber toxicity. The toxicity of dry-ground fibers was higher than the toxicity of wet-ground fibers. Grinding with or without water did not materially alter the mineralogical properties. However, dry-ground fibers contained at least 7 times more iron than wet-ground fibers. These results indicate that grinding methods significantly affect the surface concentration of iron, resulting in changes in fiber-induced reactive oxygen species generation or toxicity. Therefore, fiber preparation conditions should be accounted for when comparing the toxicity of asbestos fibers between reported studies.}, } @article {pmid27532369, year = {2016}, author = {Mercadante, S and Degiovanni, D and Casuccio, A}, title = {Symptom burden in mesothelioma patients admitted to home palliative care.}, journal = {Current medical research and opinion}, volume = {32}, number = {12}, pages = {1985-1988}, doi = {10.1080/03007995.2016.1226165}, pmid = {27532369}, issn = {1473-4877}, mesh = {Aged ; Aged, 80 and over ; Analgesics, Opioid/administration & dosage/therapeutic use ; Cancer Pain/drug therapy ; Dyspnea ; Female ; Home Care Services/*statistics & numerical data ; Humans ; Male ; *Mesothelioma/epidemiology/physiopathology/therapy ; Middle Aged ; *Palliative Care/methods/statistics & numerical data ; Retrospective Studies ; }, abstract = {CONTEXT: Mesothelioma is a very aggressive cancer that is brought on by asbestos exposure. Because there is a long latency period between exposure to asbestos and symptoms of disease, most patients with mesothelioma present with advanced disease and survive an average of 8-12 months. Thus, best supportive care should be considered critical to optimally manage these patients.

AIM: The aim of this study was to examine the epidemiological characteristics and symptom burden of mesothelioma patients when admitted to home palliative care.

METHODS: The charts of a consecutive sample of patients admitted to the home palliative care program with a diagnosis of mesothelioma in an endemic industrialized area were reviewed. The estimated survival time was about two months from admission. Epidemiological characteristics were collected. Karnofsky status, characteristics of pain and analgesic treatment at time of admission were recorded. ESAS (Edmonton Symptom Assessment System) and other clinical problems reported in the charts at admission time were also recorded.

RESULTS: Of the 674 charts reviewed, 56 patients (8.3%) had a diagnosis of mesothelioma. About three quarters of those had pain, with 18 and 2 patients with moderate and severe pain, respectively, despite receiving medium to high doses of opioids. The principal pain site was the chest. Pain was significantly associated with opioid consumption (p < .0005) and dyspnea (p = .049). Symptom burden was relevant, with a global ESAS of about 40. Pain, weakness, poor appetite, poor well-being, and dyspnea were the most frequent symptoms with the highest intensity; cough and pleural effusion were more frequently present as clinical problems.

CONCLUSION: This study shows that mesothelioma is a devastating cancer with a relevant symptom burden, and that patients were referred to palliative care late in the course of their disease, suggesting that earlier integration of palliative care should be considered to relieve suffering in all disease stages - not only at the end of life.}, } @article {pmid27516637, year = {2016}, author = {Świątkowska, B and Szeszenia-Dąbrowska, N and Wilczyńska, U}, title = {Medical monitoring of asbestos-exposed workers: experience from Poland.}, journal = {Bulletin of the World Health Organization}, volume = {94}, number = {8}, pages = {599-604}, pmid = {27516637}, issn = {1564-0604}, mesh = {*Asbestos ; Early Detection of Cancer ; *Health Services Accessibility/economics ; Humans ; Occupational Diseases/*diagnosis ; *Occupational Exposure ; Poland ; }, abstract = {In Poland, the use of asbestos was banned in 1997 and asbestos plants have been closed since then. Despite their closure, cases of asbestos-related occupational diseases among former asbestos workers are still being recorded in the Central Register of Occupational Diseases. Between 2001 and 2014, there were 2726 asbestos-related illnesses, classified and reported as diseases associated with occupational exposure to asbestos. In 2000, Poland introduced a programme called Amiantus, targeted at former asbestos-processing plant workers. The programme provided periodic medical examinations to workers and free access to medications for treatment of asbestos-related illnesses. Introduction of the programme provided additional data to generate a reliable estimation of the number of asbestos-related occupational diseases, including cancer. The average latency period for asbestosis, lung cancer and mesothelioma is about 40 years so there may still be some health impact to former workers necessitating follow-up. We present the Polish experience of implementing a medical examination programme for asbestos-exposed workers and provide a list of activities to consider when planning for such a programme.}, } @article {pmid27509983, year = {2016}, author = {Tabata, C and Tabata, R and Nakano, T}, title = {Calpeptin Prevents Malignant Pleural Mesothelioma Cell Proliferation via the Angiopoietin1/Tie2 System.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {17}, number = {7}, pages = {3405-3409}, pmid = {27509983}, issn = {2476-762X}, mesh = {Angiopoietin-1/*metabolism ; Cell Line, Tumor ; Cell Proliferation/*drug effects ; Dipeptides/*pharmacology ; Humans ; Lung/drug effects/metabolism ; Lung Neoplasms/*drug therapy/metabolism ; Mesothelioma/*drug therapy/metabolism ; Mesothelioma, Malignant ; Pleural Neoplasms/*drug therapy/metabolism ; Pulmonary Fibrosis/drug therapy/metabolism ; RNA, Messenger/metabolism ; Receptor, TIE-2/*metabolism ; }, abstract = {Malignant pleural mesothelioma (MPM), an aggressive malignant tumor of mesothelial origin associated with asbestos exposure, shows a limited response to conventional chemotherapy and radiotherapy. Therefore, the overall survival of MPM patients remains very poor. Progress in the development of therapeutic strategies for MPM has been limited. We recently reported that the calpain inhibitor, calpeptin exerted inhibitory effects on pulmonary fibrosis by inhibiting the proliferation of lung fibroblasts. In the present study, we examined the preventive effects of calpeptin on the cell growth of MPM, the origin of which is mesenchymal cells, similar to lung fibroblasts. Calpeptin inhibited the proliferation of MPM cells, but not mesothelial cells. It also prevented 1) the expression of angiopoietin (Ang)1 and Tie2 mRNA in MPM cells, but not mesothelial cells and 2) the Ang1induced proliferation of MPM cells through an NFkB dependent pathway, which may be the mechanism underlying the preventive effects of calpeptin on the growth of MPM cells. These results suggest potential clinical use of calpeptin for the treatment of MPM.}, } @article {pmid27502004, year = {2016}, author = {Hofmann-Preiß, K and Rehbock, B}, title = {[Early recognition of lung cancer in workers occupationally exposed to asbestos].}, journal = {Der Radiologe}, volume = {56}, number = {9}, pages = {810-816}, pmid = {27502004}, issn = {1432-2102}, mesh = {Asbestosis/*diagnostic imaging/*epidemiology ; Early Detection of Cancer/methods/*statistics & numerical data ; Germany/epidemiology ; Humans ; Lung Neoplasms/*diagnostic imaging/*mortality ; Mesothelioma/*diagnostic imaging/*mortality ; Mesothelioma, Malignant ; Occupational Exposure/*statistics & numerical data ; Prevalence ; Reproducibility of Results ; Risk Factors ; Sensitivity and Specificity ; Survival Rate ; Tomography, X-Ray Computed/statistics & numerical data ; }, abstract = {Despite the fact that working with asbestos and placing it on the market have been banned in Germany since 1993 according to the Ordinance on Hazardous Substances, asbestos-related diseases of the lungs and pleura are still the leading cause of death in occupational diseases. The maximum industrial usage of asbestos was reached in former West Germany in the late 1970s and in former East Germany the late 1980s. Occupational diseases, mainly mesotheliomas and lung cancer emerging now are thus caused by asbestos exposure which occurred 30-40 years earlier. It is known that the combination of smoking and asbestos exposure results in a superadditive increase in the risk to develop lung cancer. No suitable screening methods for early detection of malignant mesothelioma are currently available and the therapeutic options are still very limited; however, the national lung screening trial (NLST) has shown for the first time that by employing low-dose computed tomography (LDCT) in heavy smokers, lung cancer mortality can be significantly reduced. According to current knowledge the resulting survival benefits far outweigh the potential risks involved in the diagnostic work-up of suspicious lesions. These results in association with the recommendations of international medical societies and organizations were pivotal as the German statutory accident insurance (DGUV) decided to provide LDCT as a special occupational medical examination for workers previously exposed to asbestos and with a particularly high risk for developing lung cancer.}, } @article {pmid27501894, year = {2016}, author = {Kato, K and Gemba, K and Fujimoto, N and Aoe, K and Takeshima, Y and Inai, K and Kishimoto, T}, title = {Pleural irregularities and mediastinal pleural involvement in early stages of malignant pleural mesothelioma and benign asbestos pleural effusion.}, journal = {European journal of radiology}, volume = {85}, number = {9}, pages = {1594-1600}, doi = {10.1016/j.ejrad.2016.06.013}, pmid = {27501894}, issn = {1872-7727}, mesh = {Aged ; Asbestosis/diagnostic imaging/*pathology ; Female ; Humans ; Japan ; Lung Neoplasms/diagnostic imaging/*pathology ; Male ; Mediastinum/*pathology ; Mesothelioma/diagnostic imaging/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Pleura/diagnostic imaging/*pathology ; Pleural Effusion/diagnostic imaging/*pathology ; Retrospective Studies ; *Tomography, X-Ray Computed ; }, abstract = {OBJECTIVE: To elucidate differences in the level and localization of pleural irregularities in early malignant pleural mesothelioma (eMPM) and benign asbestos pleural effusion (BAPE) using CT.

STUDY DESIGN: Retrospective assessment of CT findings of consecutive patients with BAPE at a single centre and patients with eMPM reported in Japanese vital statistics.

METHODOLOGY: Thirty-six patients with confirmed diagnoses of BAPE and sixty-six patients with confirmed diagnoses of eMPM (mesothelioma stages T1 or T2) were included. Informed consent, CT scans, and clinical and pathologic details were obtained for all patients and were reviewed by one radiologist, two pathologists, and two pulmonologists. Asbestosis, pleural plaque, rounded atelectasis, and diffuse pleural thickening were assessed in all patients.

RESULTS: Prevalence of asbestosis, pleural plaque, rounded atelectasis, and diffuse pleural thickening was significantly higher in the BAPE group. Low-level irregularity was more common in the BAPE group (p<0.001), whereas high-level irregularity, mediastinal localization, and interlobar fissure were more prevalent in the eMPM group (p<0.001). Interlobar pleural irregularity was not observed in any patients in the BAPE group, although 55% of patients in the eMPM group showed interlobar pleural irregularity. Mediastinal pleural involvement was observed in 74% of patients in the eMPM group and had a positive predictive value of 89%.

CONCLUSION: This study demonstrates that the level and localization of plural irregularities significantly differed between patients with BAPE and eMPM. Large-scale prospective studies are needed to fully establish the diagnostic utility of such differences.}, } @article {pmid27489758, year = {2016}, author = {DeLapp, D and Chan, C and Nystrom, P}, title = {Recurrent hydropneumothorax: An unusual presentation for malignant pleural mesothelioma.}, journal = {Respiratory medicine case reports}, volume = {19}, number = {}, pages = {43-45}, pmid = {27489758}, issn = {2213-0071}, abstract = {Mesothelioma is a rare pulmonary malignancy commonly associated with asbestos exposure. Its presentation is insidious and non-specific, with complaints of chest pain, dyspnea and cough. Chest X-ray may demonstrate unilateral pleural effusion. CT and PET scans may highlight nodular pleural plaques. Diagnosis often times is difficult with negative imaging and negative pleural fluid studies. In rare cases, hydropneumothoraces may be seen. We report a case of malignant pleural mesothelioma presenting as recurrent hydropneumothorax with negative CT scan of the chest for pleural abnormalities and negative pleural fluid studies.}, } @article {pmid27484913, year = {2017}, author = {Butnor, KJ and Pavlisko, EN and Sporn, TA and Roggli, VL}, title = {Malignant peritoneal mesothelioma and Crohn disease.}, journal = {Journal of clinical pathology}, volume = {70}, number = {3}, pages = {228-232}, doi = {10.1136/jclinpath-2016-203945}, pmid = {27484913}, issn = {1472-4146}, mesh = {Aged ; Crohn Disease/*complications/pathology ; Female ; Humans ; Lung Neoplasms/*complications/pathology ; Male ; Mesothelioma/*complications/pathology ; Mesothelioma, Malignant ; Middle Aged ; Peritoneal Neoplasms/*complications/pathology ; }, abstract = {AIMS: Mesothelial reaction simulating peritoneal diffuse malignant mesothelioma (MM) has been reported in the setting of Crohn ileitis. To our knowledge, peritoneal MM arising in patients with inflammatory bowel disease (IBD) has not been reported. The purpose of this study is to report the clinicopathological characteristics of patients with peritoneal MM and IBD.

METHODS: A database of approximately 3800 MM was reviewed for cases of MM in patients with IBD.

RESULTS: Three patients (0.08%) with peritoneal MM and Crohn disease (CD) were identified, including two women and one man ranging in age from 56 to 65 years. All had a long-standing history of diarrhoea and an established diagnosis of CD of 3 years or greater duration. Two had epithelial MM and one had biphasic MM. Only one had documented asbestos exposure.

CONCLUSIONS: Peritoneal MM occurs rarely in patients with IBD, but interestingly, has only been observed in the setting of CD and not in patients with ulcerative colitis. Chronic inflammation has been associated with the development of MM in rare instances and these three cases suggest that CD with transmural inflammation may also be a precursor. The precise role of CD-related transmural inflammation in the carcinogenesis of peritoneal MM remains to be determined.}, } @article {pmid27468090, year = {2016}, author = {Barbiero, F and Giangreco, M and Pisa, FE and Negro, C and Bovenzi, M and Rosolen, V and Barbone, F}, title = {[Not Available].}, journal = {La Medicina del lavoro}, volume = {107}, number = {4}, pages = {307-314}, pmid = {27468090}, issn = {0025-7818}, mesh = {Asbestos/*adverse effects ; Cohort Studies ; Humans ; Incidence ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology/*etiology ; Occupational Diseases/*epidemiology/*etiology ; Occupational Exposure/*adverse effects ; }, abstract = {INTRODUCTION: The incidence of mesothelioma in Italy shows wide geographical variation, with the highest incidence rates in Genoa and Friuli Venezia Giulia (FVG). For mesothelioma, national standard incidence rates are not available prior to the calendar year 2006.

OBJECTIVES: To estimate the Standardized Incidence rate Ratio (SIR) of mesothelioma in a cohort of former workers undergoing health surveillance because of previous asbestos exposure, when sex-, age-, and calendar year-specific rates of the national standard are not available and the number of expected cases calculated from the regional rates is biased by the size of the study cohort.

METHODS: We conducted a sensitivity analysis in a cohort of 2,488 men. We considered every Italian cancer registry available with complete data in the period 1995-2007 (N=14). We calculated, for each year and age group, the corresponding weighted mean rate of 10 registries of North-Italy (Mean W10), the weighted mean rate of all 14 registries available (Mean W14) and considered FVG standard rate.

RESULTS: During the period 1995-2007, we observed 25 incident cases of mesothelioma with expected cases that varied between 2.00 (Mean W14) and 2.56 (FVG standard rate), with a SIR of 12.49 (CI95% 8.08-18.48) and 9.76 (CI95% 6.32-14.45) respectively.

CONCLUSIONS: Our results show that the use of FVG rates as standard does not lead to significant distortions in the calculation of the expected cases. However, distortion is remarkable in the SIRs estimation. Using a weighted mean standard incidence rate may be a valid alternative for SIR estimate when national standard rates are not available.}, } @article {pmid27466614, year = {2016}, author = {Oliver, LC and Welch, L and Frank, AL and Lemen, RA and Mutti, L}, title = {New standard for assessing asbestos exposure and its consequences?.}, journal = {Occupational and environmental medicine}, volume = {73}, number = {10}, pages = {709-710}, doi = {10.1136/oemed-2016-103693}, pmid = {27466614}, issn = {1470-7926}, mesh = {*Asbestos ; Asbestos, Amphibole ; Asbestos, Serpentine ; Humans ; Lung Neoplasms ; *Mesothelioma ; Occupational Exposure ; }, } @article {pmid27464904, year = {2016}, author = {Barbieri, PG and Sommigliana, AB}, title = {[Not Available].}, journal = {La Medicina del lavoro}, volume = {107}, number = {4}, pages = {315-326}, pmid = {27464904}, issn = {0025-7818}, mesh = {Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Asbestosis/*etiology ; Female ; Humans ; Italy ; Lung Neoplasms/*etiology ; Male ; Mesothelioma/*etiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Diseases/*etiology ; Occupational Exposure/*adverse effects ; }, abstract = {BACKGROUND: Asbestos-related diseases among shipyard workers are well known in Italy but descriptive long-term studies are limited; asbestos has been extensively used but the past exposure intensity has never been estimated because data from environmental and biological monitoring are almost absent.

OBJECTIVES: To describe the asbestos-related dis-eases (1996-2015) diagnosed among shipbuilding workers from a very important shipyard in Northern Italy, and to assess past asbestos exposure levels by cumulative dose indices, fibres and asbestos bodies.

METHODS: The cases of workers suffering from asbestos-related diseases diagnosed from 1996 to 2015 were collected on the occasion of some legal trials; the diagnosis, and the asbestos occupational and non-occupational exposure, were carefully evaluated.Lung samples were obtained from subjects, taking advantage of the autopsies; asbestos fibers were counted by means of a Scanning Electron Microscope, equipped with x-ray fluorescence microanalyses at 12.0000 amplification, and asbestos bodies by means of an Optical Microscope at 500 amplification.

RESULTS: 192 malignant mesotheliomas (6 in women), 196 lung cancers and 14 asbestosis (without cancer) were observed (1996-2015); autopsies were carried out on 80% of all subjects and 98% of mesotheliomas were confirmed by autopsies. Pleural plaques occurred on 90% of mesotheliomas and 87% of lung cancers; histologically mild asbestosis were diagnosed on 28% of mesotheliomas and 48% of lung cancers. In malignant mesothelioma and lung cancer cases respectively, the duration of occupational exposure was on average 24 and 23 ys, the latency time 48 and 46 ys, hiring at the shipyard before 1970 24 and 23 ys. Out of 114 lung analysis, the burden of asbestos fibres was >10 million for 33.3% of subjects and out of 99 lung analysis asbestos bodies was >10.000 for 71.7%; the average time since last exposure was 31 ys. Both asbestos fibres and asbestos bodies concentrations were significantly higher (GMR 2,5) among mesothelioma vs lung cancer.

CONCLUSION: A relevant number of asbestos-related diseases among shipbuilding workers, mainly mesothelioma and lung cancer, exposed in shipyard until the 1980's were identified by an active search. Thanks to several autopsies, the diagnoses of cancer are confirmed as a cause of death, and a high frequency of histological asbestosis, previously ignored,was shown. The lung burden analysis of asbestos bodies and asbestos fibres, the largest ever performed among ship-building workers, confirms the spread and relevance of asbestos exposure. The best estimate of past exposure intensity was provided by both biological indices.}, } @article {pmid27462362, year = {2016}, author = {Tomasson, K and Gudmundsson, G and Briem, H and Rafnsson, V}, title = {Malignant mesothelioma incidence by nation-wide cancer registry: a population-based study.}, journal = {Journal of occupational medicine and toxicology (London, England)}, volume = {11}, number = {}, pages = {37}, pmid = {27462362}, issn = {1745-6673}, abstract = {BACKGROUND: Malignant mesothelioma caused by asbestos exposure has a long latency period. A ban on asbestos use may not be apparent in decreased incidence in the population until after several decades. The aim was to evaluate changes in the incidence of malignant mesothelioma, and the possible impact of the asbestos ban implemented in Iceland in 1983.

METHODS: This is a population study on aggregate level; the source of data was the Icelandic Cancer Registry, the National Cause-of-Death Registry, and the National Register. Volume of asbestos import was obtained from Customs Tariff. The import figures reflect fairly accurately the amount used, as there are no mines in the country.

RESULTS: Asbestos import peaked in 1980 at 15.0 kg/capita/year, diminishing to 0.3 kg/capita/year ten years after the ban in 1983, and to zero in the most recent years. Seventy-nine per cent of the cases of malignant mesothelioma were men, and 72 % were of pleural origin. Mesothelioma incidence increased steadily from 1965 to 2014, when it reached 21.4 per million among men, and 5.6 among women. Mortality in 2014 was 22.2 per million among men, and 4.8 among women.

CONCLUSION: Malignant mesothelioma incidence and mortality increased in the population during the period, despite the ban on asbestos use from 1983. This is in agreement with the long latency time for malignant mesothelioma. In line with the previously high per capita volume of asbestos import, many buildings, equipment, and structures contain asbestos, so there is an on-going risk of asbestos exposure during maintenance, renovations and replacements. It is thus difficult to predict when the incidence of malignant mesothelioma will decrease in the future. During the last ten-year period, the incidence in Iceland was higher than the recently reported incidence in neighbouring countries.}, } @article {pmid27457873, year = {2016}, author = {Klikovits, T and Hoda, MA and Dong, Y and Arns, M and Baumgartner, B and Errhalt, P and Geltner, C and Machan, B and Pohl, W and Hutter, J and Eckmayr, J and Studnicka, M and Flicker, M and Cerkl, P and Kirchbacher, K and Klepetko, W}, title = {Management of malignant pleural mesothelioma - part 3 : Data from the Austrian Mesothelioma Interest Group (AMIG) database.}, journal = {Wiener klinische Wochenschrift}, volume = {128}, number = {17-18}, pages = {627-634}, pmid = {27457873}, issn = {1613-7671}, mesh = {Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Asbestosis/*mortality ; Austria/epidemiology ; Female ; Humans ; Male ; Mesothelioma/*diagnosis/*mortality ; Middle Aged ; Pleural Effusion, Malignant/*mortality ; Pleural Neoplasms/*mortality ; Prevalence ; *Registries ; Risk Factors ; Sex Distribution ; Survival Rate ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare but aggressive tumor originating from the pleural cavity with a strong link to previous asbestos exposure. In order to determine the demographics, diagnostics, therapeutic strategies, and prognosis of MPM patients in Austria, the Austrian Mesothelioma Interest Group (AMIG) was founded in 2011. In this report the data from the AMIG MPM database collected to date are reported.

METHODS: A prospective observational registry was initiated, including patients with histologically verified MPM diagnosed and treated at specialized centers in Austria. Patient inclusion started in January 2011 and follow-up was completed until September 2015.

RESULTS: A total number of 210 patients were included. There were 167 male and 43 female patients with a mean age of 67.0 years (SD ± 11.3) at the time of diagnosis. Asbestos exposure was confirmed in 109 (69.4 %) patients. The histological subtype was epithelioid in 141 (67.2 %), sarcomatoid in 16 (7.6 %), biphasic in 28 (13.3 %), and MPM not otherwise specified in 25 (11.9 %) patients. Of the patients, 30 (14.3 %) received best supportive care (BSC) only, 71 (33.8 %) chemotherapy (CHT) alone, four (1.9 %) radiotherapy (RT) alone, 23 (11.9 %) CHT/RT, two (0.9 %) surgery alone, and 76 (36.2 %) curative surgery within a multimodality treatment (MMT), which was more frequently performed for patients younger than 65 years and with early-stage disease (I + II). Median overall survival (OS) was 19.1 months (95 % CI 14.7-23.5). The 1‑, 3‑, and 5‑year OS rates were 66 %, 30 %, and 23 %, respectively, and OS was significantly better in patients undergoing surgery within MMT (5-year survival 5 % vs. 40 %, p = 0.001).

CONCLUSION: Patients with earlier disease stages, younger age, good performance status, and epithelioid histology were more likely to undergo MMT including surgery, which resulted in a more favorable outcome.}, } @article {pmid27457053, year = {2016}, author = {Pira, E and Romano, C and Violante, FS and Farioli, A and Spatari, G and La Vecchia, C and Boffetta, P}, title = {Updated mortality study of a cohort of asbestos textile workers.}, journal = {Cancer medicine}, volume = {5}, number = {9}, pages = {2623-2628}, pmid = {27457053}, issn = {2045-7634}, mesh = {Asbestos/*adverse effects ; Female ; Humans ; Lung Neoplasms/epidemiology/etiology/mortality ; Male ; Mesothelioma/epidemiology/etiology/mortality ; Mesothelioma, Malignant ; Neoplasms/epidemiology/*etiology/*mortality ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/epidemiology/etiology/mortality ; Population Surveillance ; Risk Factors ; *Textiles ; }, abstract = {Limited information is available on risk of peritoneal mesothelioma after asbestos exposure, and in general on the risk of cancer after cessation of asbestos exposure. We updated to 2013 the follow-up of a cohort of 1083 female and 894 male textile workers with heavy asbestos exposure (up to 100 fb/mL), often for short periods. A total of 1019 deaths were observed, corresponding to a standardized mortality ratio (SMR) of 1.68 (95% confidence interval [CI]: 1.57-1.78). SMRs were 29.1 (95% CI: 21.5-38.6) for peritoneal cancer, 2.96 (95% CI: 2.50-3.49) for lung cancer, 33.7 (95% CI: 25.7-43.4) for pleural cancer, and 3.03 (95% CI: 1.69-4.99) for ovarian cancer. For pleural and peritoneal cancer, there was no consistent pattern of risk in relation to time since last exposure, whereas for lung cancer there was an indication of a decline in risk after 25 years since last exposure. The findings of this unique cohort provide novel data for peritoneal cancer, indicating that - as for pleural cancer - the excess risk does not decline up to several decades after cessation of exposure.}, } @article {pmid27455808, year = {2016}, author = {Akatsuka, S and Toyokuni, S}, title = {[Iron function and carcinogenesis].}, journal = {Nihon rinsho. Japanese journal of clinical medicine}, volume = {74}, number = {7}, pages = {1168-1175}, pmid = {27455808}, issn = {0047-1852}, mesh = {Animals ; Cell Transformation, Neoplastic/genetics/*metabolism ; DNA Damage ; Genome ; Humans ; Iron/*metabolism ; Reactive Oxygen Species/metabolism ; }, abstract = {Though iron is an essential micronutrient for humans, the excess state is acknowledged to be associated with oncogenesis. For example, iron overload in the liver of the patients with hereditary hemocromatosis highly increases the risk of hepatocellular carcinoma. Also, as to asbestos-related mesothelioma, such kinds of asbestos with a higher iron content are considered to be more carcinogenic. Iron is a useful element, which enables fundamental functions for life such as oxygen carrying and electron transport. However, in the situation where organisms are unable to have good control of it, iron turns into a dangerous element which catalyzes generation of reactive oxygen. In this review, I first outline the relationships between iron and cancer in general, then give an explanation about iron-related animal carcinogenesis models.}, } @article {pmid27454480, year = {2016}, author = {Yap, HS and Klebe, S and Rose, A}, title = {Endobronchial Diagnosis of a Malignant Mesothelioma.}, journal = {Journal of bronchology & interventional pulmonology}, volume = {23}, number = {3}, pages = {e30-2}, doi = {10.1097/LBR.0000000000000294}, pmid = {27454480}, issn = {1948-8270}, mesh = {Asbestos/*adverse effects ; Conservative Treatment ; Endoscopic Ultrasound-Guided Fine Needle Aspiration/*methods ; Humans ; Lung Neoplasms/*diagnosis/etiology ; Male ; Mesothelioma/*diagnosis/etiology ; Mesothelioma, Malignant ; Middle Aged ; Palliative Care ; Thoracic Surgery, Video-Assisted/*methods ; }, } @article {pmid27453164, year = {2016}, author = {Carbone, M and Kanodia, S and Chao, A and Miller, A and Wali, A and Weissman, D and Adjei, A and Baumann, F and Boffetta, P and Buck, B and de Perrot, M and Dogan, AU and Gavett, S and Gualtieri, A and Hassan, R and Hesdorffer, M and Hirsch, FR and Larson, D and Mao, W and Masten, S and Pass, HI and Peto, J and Pira, E and Steele, I and Tsao, A and Woodard, GA and Yang, H and Malik, S}, title = {Consensus Report of the 2015 Weinman International Conference on Mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {11}, number = {8}, pages = {1246-1262}, pmid = {27453164}, issn = {1556-1380}, support = {P30 CA071789/CA/NCI NIH HHS/United States ; R01 CA160715/CA/NCI NIH HHS/United States ; R01 CA198138/CA/NCI NIH HHS/United States ; U01 CA111295/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers, Tumor ; Consensus ; Environmental Exposure ; Female ; Genes, BRCA1 ; Humans ; Lung Neoplasms/diagnosis/*etiology/genetics/mortality ; Male ; Mesothelioma/diagnosis/*etiology/genetics/mortality ; Mesothelioma, Malignant ; Mutation ; Osteopontin/blood ; Tumor Suppressor Proteins/genetics ; Ubiquitin Thiolesterase/genetics ; }, abstract = {On November 9 and 10, 2015, the International Conference on Mesothelioma in Populations Exposed to Naturally Occurring Asbestiform Fibers was held at the University of Hawaii Cancer Center in Honolulu, Hawaii. The meeting was cosponsored by the International Association for the Study of Lung Cancer, and the agenda was designed with significant input from staff at the U.S. National Cancer Institute and National Institute of Environmental Health Sciences. A multidisciplinary group of participants presented updates reflecting a range of disciplinary perspectives, including mineralogy, geology, epidemiology, toxicology, biochemistry, molecular biology, genetics, public health, and clinical oncology. The group identified knowledge gaps that are barriers to preventing and treating malignant mesothelioma (MM) and the required next steps to address barriers. This manuscript reports the group's efforts and focus on strategies to limit risk to the population and reduce the incidence of MM. Four main topics were explored: genetic risk, environmental exposure, biomarkers, and clinical interventions. Genetics plays a critical role in MM when the disease occurs in carriers of germline BRCA1 associated protein 1 mutations. Moreover, it appears likely that, in addition to BRCA1 associated protein 1, other yet unknown genetic variants may also influence the individual risk for development of MM, especially after exposure to asbestos and related mineral fibers. MM is an almost entirely preventable malignancy as it is most often caused by exposure to commercial asbestos or mineral fibers with asbestos-like health effects, such as erionite. In the past in North America and in Europe, the most prominent source of exposure was related to occupation. Present regulations have reduced occupational exposure in these countries; however, some people continue to be exposed to previously installed asbestos in older construction and other settings. Moreover, an increasing number of people are being exposed in rural areas that contain noncommercial asbestos, erionite, and other mineral fibers in soil or rock (termed naturally occurring asbestos [NOA]) and are being developed. Public health authorities, scientists, residents, and other affected groups must work together in the areas where exposure to asbestos, including NOA, has been documented in the environment to mitigate or reduce this exposure. Although a blood biomarker validated to be effective for use in screening and identifying MM at an early stage in asbestos/NOA-exposed populations is not currently available, novel biomarkers presented at the meeting, such as high mobility group box 1 and fibulin-3, are promising. There was general agreement that current treatment for MM, which is based on surgery and standard chemotherapy, has a modest effect on the overall survival (OS), which remains dismal. Additionally, although much needed novel therapeutic approaches for MM are being developed and explored in clinical trials, there is a critical need to invest in prevention research, in which there is a great opportunity to reduce the incidence and mortality from MM.}, } @article {pmid27445546, year = {2016}, author = {Ross, RM}, title = {Software for Apportionment of Asbestos-Related Mesotheliomas.}, journal = {Canadian respiratory journal}, volume = {2016}, number = {}, pages = {5340676}, pmid = {27445546}, issn = {1916-7245}, mesh = {Animals ; Asbestos/administration & dosage/*adverse effects ; Cost Allocation ; Environmental Exposure/*adverse effects ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; *Software ; Time Factors ; }, abstract = {Patients with an asbestos-related mesothelioma may be legally entitled to financial compensation. In this context, a physician may be called upon to apportion the contribution of an asbestos containing product or facility where there was asbestos exposure in the development of that individual's mesothelioma. This task is mathematically not simple. It is a complex function of each and the entire individual's above-background asbestos exposures. Factors to be considered for each of these exposures are the amount of exposure to mesotheliogenic fibers, each of the asbestos containing products' potency to cause mesothelioma, and the time period when the exposures occurred relative to when the mesothelioma was diagnosed. In this paper, the known factors related to asbestos-related mesothelioma risk are briefly reviewed and the software that is downloadable and fully functional in a Windows® environment is also provided. This software allows for rapid assessment of relative contributions and deals with the somewhat tedious mathematical calculations. With this software and a reasonable occupational history, if it is decided that the mesothelioma was due to above-background asbestos exposure, the contribution of an asbestos containing product or a time period of asbestos exposure can be apportioned.}, } @article {pmid27436254, year = {2016}, author = {Ferrante, P and Mastrantonio, M and Uccelli, R and Corfiati, M and Marinaccio, A}, title = {[Pleural mesothelioma mortality in Italy: time series reconstruction (1970-2009) and comparison with incidence (2003-2008)].}, journal = {Epidemiologia e prevenzione}, volume = {40}, number = {3-4}, pages = {205-214}, doi = {10.19191/EP16.3-4.P205.087}, pmid = {27436254}, issn = {1120-9763}, mesh = {Asbestos/*adverse effects ; Humans ; Incidence ; Italy/epidemiology ; Mesothelioma/diagnosis/*etiology/*mortality ; Occupational Exposure ; Pleural Neoplasms/diagnosis/*etiology/*mortality ; Population Surveillance ; Registries ; Retrospective Studies ; Survival Rate ; }, abstract = {BACKGROUND: the large amount of asbestos used in many Countries (including Italy) is causing an epidemic of asbestos related diseases, which is still ongoing because of their long latency.

OBJECTIVES: this study is aimed at reconstructing Italian time series of deaths for mesothelioma in the period 1970-2009 and comparing Italian incidence and mortality data.

deaths for pleural cancer (1970-2003,2006-2009) and mesothelioma (2003, 2006-2009) were recorded by the Italian Institute of Statistics (Istat) and provided by the Italian National Agency for New Technologies, Energy and the Environment (ENEA), incidence cases (1993-2008) were provided by the Italian mesotheliomas register (ReNaM) at the Italian National Workers' Compensation Authority (Inail). For the period before ICD-10 implementation (1970-2002) and when Istat data (2004-2005) are lacking, mesothelioma deaths were estimated through statistical models (logistic, Poisson). National incidence and mortality data were compared during the overlapping period (2003, 2006-2008).

RESULTS: the mortality curve strongly rises from 1970 and seems to be smoothed in the last years. Mortality caused by mesothelioma and incident cases with certain diagnosis are overlapping, as are mortality due to pleural cancer other than mesothelioma and mesothelioma incidence with uncertain diagnosis (probable/possible).

CONCLUSIONS: this epidemiological analysis of deaths encoded as pleural tumour suggests to carefully investigate space-temporal distribution before excluding they could be mesotheliomas. Some new lights have been thrown on the statistical behaviour of mesothelioma mortality.}, } @article {pmid27436246, year = {2016}, author = {Mirabelli, D}, title = {[Every little bit counts in order to protect asbestos business].}, journal = {Epidemiologia e prevenzione}, volume = {40}, number = {3-4}, pages = {154-155}, doi = {10.19191/EP16.3-4.P154.082}, pmid = {27436246}, issn = {1120-9763}, mesh = {Asbestos/*adverse effects ; *Carcinogens ; Commerce/standards ; *Extraction and Processing Industry/standards ; Humans ; Italy/epidemiology ; Mesothelioma/*etiology/mortality/prevention & control ; Occupational Exposure/*adverse effects ; Periodicals as Topic ; Pleural Neoplasms/*etiology/mortality/prevention & control ; Risk Assessment ; Risk Factors ; Time Factors ; World Health Organization ; }, } @article {pmid27431778, year = {2017}, author = {Bonelli, MA and Fumarola, C and La Monica, S and Alfieri, R}, title = {New therapeutic strategies for malignant pleural mesothelioma.}, journal = {Biochemical pharmacology}, volume = {123}, number = {}, pages = {8-18}, doi = {10.1016/j.bcp.2016.07.012}, pmid = {27431778}, issn = {1873-2968}, mesh = {Antineoplastic Agents/therapeutic use ; Humans ; Immunotherapy ; Lung Neoplasms/genetics/immunology/*therapy ; Mesothelioma/genetics/immunology/*therapy ; Mesothelioma, Malignant ; Pleural Neoplasms/genetics/immunology/*therapy ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare and aggressive malignant disease affecting the mesothelium, commonly associated to asbestos exposure. Therapeutic actions are limited due to the late stage at which most patients are diagnosed and the intrinsic chemo-resistance of the tumor. The recommended systemic therapy for MPM is cisplatin/pemetrexed regimen with a mean overall survival of about 12months and a median progression free survival of less than 6months. Considering that the incidence of this tumor is expected to increase in the next decade and that its prognosis is poor, novel therapeutic approaches are urgently needed. For some tumors, such as lung cancer and breast cancer, druggable oncogenic alterations have been identified and targeted therapy is an important option for these patients. For MPM, clinical guidelines do not recommend biological targeted therapy, mainly because of poor target definition or inappropriate trial design. Further studies are required for a full comprehension of the molecular pathogenesis of MPM and for the development of new target agents. This review updates pre-clinical and clinical data on the efficacy of targeted therapy and immune checkpoint inhibition in the treatment of mesothelioma. Finally, future perspectives in this deadly disease are also discussed.}, } @article {pmid27431629, year = {2016}, author = {Morimoto, C and Ohnuma, K}, title = {[Development of New Therapy for Malignant Mesothelioma Based on CD26 Molecule].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {43}, number = {7}, pages = {855-862}, pmid = {27431629}, issn = {0385-0684}, mesh = {Animals ; Clinical Trials, Phase I as Topic ; Dipeptidyl Peptidase 4/chemistry/immunology/*metabolism ; Drug Design ; Humans ; Lung Neoplasms/*drug therapy/metabolism ; Mesothelioma/*drug therapy/metabolism ; Mesothelioma, Malignant ; Mice ; Signal Transduction ; T-Lymphocytes/immunology ; }, abstract = {CD26 is a 110 kDa, type II transmembrane glycoprotein with dipeptidyl peptidase IV activity and is capable of cleaving Nterminal dipeptides with either L-proline or L-alanine at the penultimate position. Malignant mesothelioma(MM)is an aggressive malignancy arising from the mesothelial cells. It is generally associated with a history of asbestos exposure and has a very poor prognosis. Due to lack of efficacy of conventional treatments, novel therapeutic strategies are urgently needed to improve outcomes. Recently we showed that CD26 is preferentially expressed on epithelial type of MM cells but not on normal mesothelial cells. We have developed a highly biological active humanized anti-CD26 monoclonal antibody(mAb)and have published previously extensive in vivo data demonstrating the anti-tumor activity of humanized anti-CD26 mAb(YS110)in mouse xenograft models. The use of a humanized anti-CD26 mAb may therefore be a rational therapy for patients with MM. The first-in-human(FIH)phase I study performed in France demonstrates that humanized anti-CD26 therapy is generally well-tolerated with preliminary evidence of activity in patients with advanced/refractory CD26-expressing cancers, particularly refractory malignant mesothelioma. From the above results, the phase I clinical trial for malignant mesothelioma in Japan is to be started in the very near future.}, } @article {pmid27422997, year = {2016}, author = {He, X and Despeaux, E and Stueckle, TA and Chi, A and Castranova, V and Dinu, CZ and Wang, L and Rojanasakul, Y}, title = {Role of mesothelin in carbon nanotube-induced carcinogenic transformation of human bronchial epithelial cells.}, journal = {American journal of physiology. Lung cellular and molecular physiology}, volume = {311}, number = {3}, pages = {L538-49}, pmid = {27422997}, issn = {1522-1504}, support = {R01 EB018857/EB/NIBIB NIH HHS/United States ; P20 RR016440/RR/NCRR NIH HHS/United States ; R01 ES022968/ES/NIEHS NIH HHS/United States ; P30 RR032138/RR/NCRR NIH HHS/United States ; P20 RR016477/RR/NCRR NIH HHS/United States ; P20 GM103434/GM/NIGMS NIH HHS/United States ; P30 GM103488/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Bronchioles/pathology ; Carcinogens/*toxicity ; Cell Line ; Cell Movement ; Cell Proliferation ; Cell Transformation, Neoplastic ; Cyclin E/genetics/metabolism ; Epithelial Cells/*metabolism/pathology ; GPI-Linked Proteins/*physiology ; Gene Expression ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/*metabolism/pathology ; Mesothelin ; Mice, Inbred NOD ; Mice, Nude ; Mice, SCID ; Nanotubes, Carbon/*toxicity ; Neoplasm Transplantation ; }, abstract = {Carbon nanotubes (CNTs) have been likened to asbestos in terms of morphology and toxicity. CNT exposure can lead to pulmonary fibrosis and promotion of tumorigenesis. However, the mechanisms underlying CNT-induced carcinogenesis are not well defined. Mesothelin (MSLN) is overexpressed in many human tumors, including mesotheliomas and pancreatic and ovarian carcinomas. In this study, the role of MSLN in the carcinogenic transformation of human bronchial epithelial cells chronically exposed to single-walled CNT (BSW) was investigated. MSLN overexpression was found in human lung tumors, lung cancer cell lines, and BSW cells. The functional role of MSLN in the BSW cells was then investigated by using stably transfected MSLN knockdown (BSW shMSLN) cells. MSLN knockdown resulted in significantly decreased invasion, migration, colonies on soft agar, and tumor sphere formation. In vivo, BSW shMSLN cells formed smaller primary tumors and less metastases. The mechanism by which MSLN contributes to these more aggressive behaviors was investigated by using ingenuity pathway analysis, which predicted that increased MSLN could induce cyclin E expression. We found that BSW shMSLN cells had decreased cyclin E, and their proliferation rate was reverted to nearly that of untransformed cells. Cell cycle analysis showed that the BSW shMSLN cells had an increased G2 population and a decreased S phase population, which is consistent with the decreased rate of proliferation. Together, our results indicate a novel role of MSLN in the malignant transformation of bronchial epithelial cells following CNT exposure, suggesting its utility as a potential biomarker and drug target for CNT-induced malignancies.}, } @article {pmid27418105, year = {2016}, author = {Chéné, AL and d'Almeida, S and Blondy, T and Tabiasco, J and Deshayes, S and Fonteneau, JF and Cellerin, L and Delneste, Y and Grégoire, M and Blanquart, C}, title = {Pleural Effusions from Patients with Mesothelioma Induce Recruitment of Monocytes and Their Differentiation into M2 Macrophages.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {11}, number = {10}, pages = {1765-1773}, doi = {10.1016/j.jtho.2016.06.022}, pmid = {27418105}, issn = {1556-1380}, mesh = {Cell Differentiation ; Cell Line, Tumor ; Female ; Humans ; Immunohistochemistry ; Lung Neoplasms/*complications/pathology ; Macrophages/*metabolism ; Male ; Mesothelioma/*complications/pathology ; Mesothelioma, Malignant ; Monocytes/*metabolism ; }, abstract = {INTRODUCTION: Mesothelioma is a rare and aggressive cancer related to asbestos exposure. We recently showed that pleural effusions (PEs) from patients with mesothelioma contain high levels of the C-C motif chemokine ligand 2 (CCL2) inflammatory chemokine. In the present work, we studied the effect of CCL2 contained in mesothelioma samples, particularly on monocyte recruitment. Then, we studied the fate of these monocytes in malignant pleural mesothelioma (MPM) PEs and their impact on tumor cells' properties.

METHODS: The implication of CCL2 in monocyte recruitment was evaluated using transmigration assays and a CCL2 blocking antibody. The phenotype of macrophages was determined by flow cytometry and enzyme-linked immunosorbent assay. Immunohistochemical analysis was used to support the results. Cocultures of macrophages with mesothelioma cells were performed to study cancer cell proliferation and resistance to treatment.

RESULTS: We showed that CCL2 is a major factor of monocyte recruitment induced by MPM samples. Macrophages obtained in MPM samples were M2 macrophages (high CD14, high CD163, and interleukin-10 secretion after activation). The colony-stimulating factor 1 receptor/macrophage colony-stimulating factor (M-CSF) pathway is implicated in M2 polarization, and high levels of M-CSF were measured in MPM samples compared with benign PE (4.17 ± 2.75 ng/mL and 1.94 ± 1.47 ng/mL, respectively). Immunohistochemical analysis confirmed the presence of M2 macrophages in pleural and peritoneal mesothelioma. Finally, we showed that M2 macrophages increased mesothelioma cell proliferation and resistance to treatment.

CONCLUSIONS: These results demonstrate the implication of CCL2 in MPM pathogenesis and designate M-CSF as a new potential biomarker of MPM. This study also identifies CCL2 and colony-stimulating factor 1 receptor/M-CSF as interesting new targets to modulate pro-tumorigenic properties of the tumor microenvironment.}, } @article {pmid27408810, year = {2016}, author = {Lin, RC and Kirschner, MB and Cheng, YY and van Zandwijk, N and Reid, G}, title = {MicroRNA gene expression signatures in long-surviving malignant pleural mesothelioma patients.}, journal = {Genomics data}, volume = {9}, number = {}, pages = {44-49}, pmid = {27408810}, issn = {2213-5960}, abstract = {Malignant pleural mesothelioma (MPM) is a tumor originating in the mesothelium, the membrane lining the thoracic cavities, and is induced by exposure to asbestos. Australia suffers one of the world's highest rates of MPM and the incidence is yet to peak. The prognosis for patients with MPM is poor and median survival following diagnosis is 4-18 months. Currently, no or few effective therapies exist for MPM. Trials of targeted agents such as antiangiogenic agents (VEGF, EGFR) or ribonuclease inhibitors (ranpirnase) largely failed to show efficacy in MPM Tsao et al. (2009) [1]. A recent study, however, showed that cisplatin/pemetrexed + bevacizumab (a recombinant humanized monoclonal antibody that inhibit VEGF) treatment has a survival benefit of 2.7 months Zalcman et al. (2016) [2]. It remains to be seen if this targeted therapy will be accepted as a new standard for MPM. Thus the unmet needs of MPM patients remain very pronounced and almost every patient will be confronted with drug resistance and recurrence of disease. We have identified unique gene signatures associated with prolonged survival in mesothelioma patients undergoing radical surgery (EPP, extrapleural pneumonectomy), as well as patients who underwent palliative surgery (pleurectomy/decortication). In addition to data published in Molecular Oncology, 2015;9:715-26 (GSE59180) Kirschner et al. (2015) , we describe here additional data using a system-based approach that support our previous observations. This data provides a resource to further explore microRNA dynamics in MPM.}, } @article {pmid27405014, year = {2016}, author = {Domínguez-Malagón, H and Cano-Valdez, AM and González-Carrillo, C and Campos-Salgado, YE and Lara-Garcia, A and Lopez-Mejia, M and Corona-Cruz, JF and Arrieta, O}, title = {Diagnostic efficacy of electron microscopy and pleural effusion cytology for the distinction of pleural mesothelioma and lung adenocarcinoma.}, journal = {Ultrastructural pathology}, volume = {40}, number = {5}, pages = {254-260}, doi = {10.1080/01913123.2016.1195469}, pmid = {27405014}, issn = {1521-0758}, mesh = {Adenocarcinoma/*diagnosis/ultrastructure ; Adenocarcinoma of Lung ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/analysis ; Cytodiagnosis ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; Lung Neoplasms/*diagnosis/ultrastructure ; Male ; Mesothelioma/*diagnosis/ultrastructure ; Microscopy, Electron, Transmission ; Middle Aged ; Pleural Effusion, Malignant/*pathology ; Pleural Neoplasms/*diagnosis/ultrastructure ; }, abstract = {The diagnosis of malignant pleural mesothelioma (MPM) is challenging and requires immunohistochemistry or electron microscopy assays to specifically differentiate MPM from lung adenocarcinoma. An ultrastructural study of fresh tissue is considered to be the "gold standard." In most cases, the first diagnostic approach is performed on pleural effusion, and in some patients, this is the only available sample for diagnosis. The aim of the present study is to evaluate if an examination of pleural effusion samples based on electron microscopy (EMpe) is a useful tool for the differential diagnosis of MPM and lung adenocarcinoma. An EMpe study was performed in 25 pleural effusion samples. Histological and immunohistochemical markers confirmed the diagnosis of either mesothelioma (5) or adenocarcinoma (20). Of the five cases that were diagnosed with mesothelioma, two samples (40%) showed cells with "bushy" microvilli, which are characteristic of mesothelioma, by EMpe, and three were acellular (60%). Of the 20 cases of adenocarcinoma, EMpe showed cells with short microvilli in 9 (45%), and 11 were acellular (55%). EMpe identifies unequivocal morphological changes that are useful for the differential diagnosis of MPM or adenocarcinoma when the pleural effusion sample contains evaluable tumor cells.}, } @article {pmid27397058, year = {2017}, author = {Gaffney, SH and Grespin, M and Garnick, L and Drechsel, DA and Hazan, R and Paustenbach, DJ and Simmons, BD}, title = {Anthophyllite asbestos: state of the science review.}, journal = {Journal of applied toxicology : JAT}, volume = {37}, number = {1}, pages = {38-49}, doi = {10.1002/jat.3356}, pmid = {27397058}, issn = {1099-1263}, mesh = {Animals ; Asbestos, Amphibole/*toxicity ; Environmental Exposure/*adverse effects/analysis ; Environmental Pollutants/*toxicity ; Humans ; Lung Neoplasms/*chemically induced/epidemiology ; Mesothelioma/*chemically induced/epidemiology ; *Mining ; }, abstract = {Anthophyllite is an amphibole form of asbestos historically used in only a limited number of products. No published resource currently exists that offers a complete overview of anthophyllite toxicity or of its effects on exposed human populations. We performed a review focusing on how anthophyllite toxicity was understood over time by conducting a comprehensive search of publicly available documents that discussed the use, mining, properties, toxicity, exposure and potential health effects of anthophyllite. Over 200 documents were identified; 114 contained relevant and useful information which we present chronologically in this assessment. Our analysis confirms that anthophyllite toxicity has not been well studied compared to other asbestos types. We found that toxicology studies in animals from the 1970s onward have indicated that, at sufficient doses, anthophyllite can cause asbestosis, lung cancer and mesothelioma. Studies of Finnish anthophyllite miners, conducted in the 1970s, found an increased incidence of asbestosis and lung cancer, but not mesothelioma. Not until the mid-1990s was an epidemiological link with mesothelioma in humans observed. Its presence in talc has been of recent significance in relation to potential asbestos exposure through the use of talc-containing products. Characterizing the health risks of anthophyllite is difficult, and distinguishing between its asbestiform and non-asbestiform mineral form is essential from both a toxicological and regulatory perspective. Anthophyllite toxicity has generally been assumed to be similar to other amphiboles from a regulatory standpoint, but some notable exceptions exist. In order to reach a more clear understanding of anthophyllite toxicity, significant additional study is needed. Copyright © 2016 John Wiley & Sons, Ltd.}, } @article {pmid27388398, year = {2016}, author = {Creaney, J and Lee, YC}, title = {Diagnoses (Not Diagnosis) of Pleural Effusion. Time to Consider Concurrent Etiologies.}, journal = {Annals of the American Thoracic Society}, volume = {13}, number = {7}, pages = {1003-1004}, doi = {10.1513/AnnalsATS.201604-320ED}, pmid = {27388398}, issn = {2325-6621}, mesh = {*Exudates and Transudates ; Humans ; *Pleural Effusion ; }, } @article {pmid27388204, year = {2016}, author = {Soeberg, MJ and Luong, MA and Tran, VT and Tran, AT and Nguyen, TT and Bui, D and Nguyen, TH and Takahashi, K and van Zandwijk, N}, title = {Estimating the incidence of malignant mesothelioma in Vietnam: a pilot descriptive cancer registration study.}, journal = {International journal of occupational and environmental health}, volume = {22}, number = {2}, pages = {167-172}, pmid = {27388204}, issn = {2049-3967}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asbestos ; Child ; Environmental Exposure ; Female ; Humans ; Incidence ; Lung Neoplasms/diagnostic imaging/*epidemiology/pathology ; Male ; Mesothelioma/diagnostic imaging/*epidemiology/pathology ; Mesothelioma, Malignant ; Middle Aged ; Radiography ; Registries ; Vietnam/epidemiology ; Young Adult ; }, abstract = {INTRODUCTION: Global asbestos consumption has shifted toward lower income countries, particularly in the Asian region including Vietnam where asbestos and asbestos-containing products have been imported since the late 1960s.

METHODS: This pilot descriptive epidemiological study aimed to provide contemporary estimates of malignant mesothelioma incidence (histological subtype M9050/3; ICD-O-3) by gender and age group as recorded across nine cancer registries in Vietnam.

RESULTS: We identified 148 incident cases of malignant mesothelioma during 1987-2013. The majority of cases were recorded in the Hanoi region (n = 93) and were aged 55 years or older (n = 96).

DISCUSSION: By carefully reviewing existing cancer registry records in Vietnam, we identified a larger number of malignant mesothelioma cases than previously estimated. We recommend the use of cancer registry data in tracking future asbestos-related disease in Vietnam.}, } @article {pmid27381209, year = {2016}, author = {Azzopardi, M and Thomas, R and Muruganandan, S and Lam, DC and Garske, LA and Kwan, BC and Rashid Ali, MR and Nguyen, PT and Yap, E and Horwood, FC and Ritchie, AJ and Bint, M and Tobin, CL and Shrestha, R and Piccolo, F and De Chaneet, CC and Creaney, J and Newton, RU and Hendrie, D and Murray, K and Read, CA and Feller-Kopman, D and Maskell, NA and Lee, YC}, title = {Protocol of the Australasian Malignant Pleural Effusion-2 (AMPLE-2) trial: a multicentre randomised study of aggressive versus symptom-guided drainage via indwelling pleural catheters.}, journal = {BMJ open}, volume = {6}, number = {7}, pages = {e011480}, pmid = {27381209}, issn = {2044-6055}, mesh = {Adult ; Aged ; Australia/epidemiology ; Body Fluids ; *Catheters, Indwelling ; Clinical Protocols ; *Drainage/methods ; Dyspnea/physiopathology/*therapy ; Female ; Hong Kong/epidemiology ; Humans ; Lung Neoplasms/epidemiology/*prevention & control ; Male ; Mesothelioma/epidemiology/*prevention & control ; Mesothelioma, Malignant ; New Zealand/epidemiology ; Pleural Effusion, Malignant/epidemiology/physiopathology/*therapy ; *Pleurodesis/methods ; Prospective Studies ; Quality of Life ; Talc ; Treatment Outcome ; }, abstract = {INTRODUCTION: Malignant pleural effusions (MPEs) can complicate most cancers, causing dyspnoea and impairing quality of life (QoL). Indwelling pleural catheters (IPCs) are a novel management approach allowing ambulatory fluid drainage and are increasingly used as an alternative to pleurodesis. IPC drainage approaches vary greatly between centres. Some advocate aggressive (usually daily) removal of fluid to provide best symptom control and chance of spontaneous pleurodesis. Daily drainages however demand considerably more resources and may increase risks of complications. Others believe that MPE care is palliative and drainage should be performed only when patients become symptomatic (often weekly to monthly). Identifying the best drainage approach will optimise patient care and healthcare resource utilisation.

METHODS AND ANALYSIS: A multicentre, open-label randomised trial. Patients with MPE will be randomised 1:1 to daily or symptom-guided drainage regimes after IPC insertion. Patient allocation to groups will be stratified for the cancer type (mesothelioma vs others), performance status (Eastern Cooperative Oncology Group status 0-1 vs ≥2), presence of trapped lung (vs not) and prior pleurodesis (vs not). The primary outcome is the mean daily dyspnoea score, measured by a 100 mm visual analogue scale (VAS) over the first 60 days. Secondary outcomes include benefits on physical activity levels, rate of spontaneous pleurodesis, complications, hospital admission days, healthcare costs and QoL measures. Enrolment of 86 participants will detect a mean difference of VAS score of 14 mm between the treatment arms (5% significance, 90% power) assuming a common between-group SD of 18.9 mm and a 10% lost to follow-up rate.

ETHICS AND DISSEMINATION: The Sir Charles Gairdner Group Human Research Ethics Committee has approved the study (number 2015-043). Results will be published in peer-reviewed journals and presented at scientific meetings.

TRIAL REGISTRATION NUMBER: ACTRN12615000963527; Pre-results.}, } @article {pmid27376267, year = {2016}, author = {Driml, J and Pulford, E and Moffat, D and Karapetis, C and Kao, S and Griggs, K and Henderson, DW and Klebe, S}, title = {Usefulness of Aquaporin 1 as a Prognostic Marker in a Prospective Cohort of Malignant Mesotheliomas.}, journal = {International journal of molecular sciences}, volume = {17}, number = {7}, pages = {}, pmid = {27376267}, issn = {1422-0067}, mesh = {Adult ; Aged ; Aged, 80 and over ; Aquaporin 1/*metabolism ; Biomarkers, Tumor/*metabolism ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lung Neoplasms/*diagnosis/mortality/pathology ; Male ; Mesothelioma/*diagnosis/mortality/pathology ; Mesothelioma, Malignant ; Middle Aged ; Multivariate Analysis ; Prognosis ; Proportional Hazards Models ; Prospective Studies ; }, abstract = {(1) BACKGROUND: Malignant mesothelioma (MM) is an aggressive tumour of the serosal membranes, associated with exposure to asbestos. Survival is generally poor, but prognostication for individual patients is difficult. We recently described Aquaporin 1 (AQP1) as independent prognostic factor in two separate retrospective cohorts of MM patients. Here we assess the usefulness of AQP1 prospectively, and determine the inter-observer agreement in assessing AQP1 scores; (2) METHODS: A total of 104 consecutive cases of MM were included. Sufficient tissue for immunohistochemistry was available for 100 cases, and these cases were labelled for AQP1. Labelling was assessed by two pathologists. Complete clinical information and follow up was available for 91 cases; (3) RESULTS: Labelling of ≥50% of tumour cells for AQP indicated improved prognosis in a univariate model (median survival 13 versus 8 months, p = 0.008), but the significance was decreased in a multivariate analysis. Scoring for AQP1 was robust, with an inter-observer kappa value of 0.722, indicating substantial agreement between observers; (4) CONCLUSION: AQP1 is a useful prognostic marker that can be easily incorporated in existing diagnostic immunohistochemical panels and which can be reliably interpreted by different pathologists.}, } @article {pmid27372959, year = {2016}, author = {Franklin, P and Reid, A and Olsen, N and Peters, S and de Klerk, N and Brims, F and Threlfall, T and Murray, R and Musk, AB}, title = {Incidence of malignant mesothelioma in Aboriginal people in Western Australia.}, journal = {Australian and New Zealand journal of public health}, volume = {40}, number = {4}, pages = {383-387}, doi = {10.1111/1753-6405.12542}, pmid = {27372959}, issn = {1753-6405}, mesh = {Adult ; Aged ; Asbestos ; Asbestos, Crocidolite ; Causality ; Female ; Humans ; Incidence ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology ; Mesothelioma, Malignant ; Middle Aged ; Mining/statistics & numerical data ; Native Hawaiian or Other Pacific Islander/*statistics & numerical data ; Occupational Exposure/*statistics & numerical data ; Registries/statistics & numerical data ; Western Australia/epidemiology ; }, abstract = {OBJECTIVES: To describe the incidence of malignant mesothelioma (MM) in Aboriginal people in Western Australia (WA) and determine the main routes of exposure to asbestos in this population.

METHODS: All MM cases in Western Australia, as well as the primary source of asbestos exposure, are recorded in the WA Mesothelioma Register. Aboriginal cases up to the end of 2013 were extracted from the register and compared with non-Aboriginal cases with respect to the primary means/source of exposure. Age-standardised incidence rates for each decade from 1980 were calculated for both Aboriginals and non-Aboriginals. Age-standardised mortality rates were calculated for the period 1994-2008 and compared with international rates.

RESULTS: There were 39 cases (77% male) of MM among WA Aboriginal people. Twenty-six (67%) were a direct result of the mining of crocidolite at Wittenoom and the subsequent contamination of the surrounding lands. Of the non-Aboriginal MM cases (n = 2070, 86.3% male), fewer than 25% can be attributed to Wittenoom. Aboriginals had consistently higher 10-year incidence rates than non-Aboriginals and, when compared to world populations, the highest mortality rate internationally.

CONCLUSION: When incidence rates in Aboriginal people are compared with non-Aboriginal people, the Wittenoom mining operation has had a disproportionate effect on MM incidence in the local Aboriginal population.}, } @article {pmid27354997, year = {2016}, author = {Hancock, KL and Clinton, CM and Dinkelspiel, HE and Saab, J and Schneider, B and Caputo, TA}, title = {A case of mesothelioma masquerading pre-operatively as ovarian cancer and brief review of the literature.}, journal = {Gynecologic oncology reports}, volume = {17}, number = {}, pages = {26-28}, pmid = {27354997}, issn = {2352-5789}, abstract = {BACKGROUND: Malignant peritoneal mesothelioma (MPM) can masquerade as an ovarian epithelial neoplasm, with very similar presenting clinical symptoms and imaging findings. The gold standard in differentiating between these two diagnoses lies in tissue pathology.

CASE REPORT: This is a case of MPM that was initially misdiagnosed as ovarian cancer based on family history, imaging, and surgical findings. Tissue diagnosis preoperatively would have changed the planned procedure. Retrospectively, after the diagnosis of MPM, the patient was found to have had an indirect exposure to asbestos through her father.

CONCLUSIONS: This case highlights the importance of keeping a broad differential when diagnosing ovarian malignancies, collecting both family and social histories (including screening for exposure to asbestos), and the benefit of obtaining tissue diagnosis when MPM is suspected.}, } @article {pmid27349291, year = {2016}, author = {Musumeci, G and Loreto, C and Giunta, S and Rapisarda, V and Szychlinska, MA and Imbesi, R and Castorina, A and Annese, T and Castorina, S and Castrogiovanni, P and Ribatti, D}, title = {Angiogenesis correlates with macrophage and mast cell infiltration in lung tissue of animals exposed to fluoro-edenite fibers.}, journal = {Experimental cell research}, volume = {346}, number = {1}, pages = {91-98}, doi = {10.1016/j.yexcr.2016.06.017}, pmid = {27349291}, issn = {1090-2422}, mesh = {Animals ; Antigens, CD/metabolism ; Asbestos, Amphibole/*toxicity ; Blotting, Western ; Densitometry ; Female ; Immunohistochemistry ; Lung/drug effects/*pathology ; Macrophages/drug effects/*metabolism ; Male ; Mast Cells/drug effects/enzymology/*metabolism ; *Neovascularization, Physiologic/drug effects ; Sheep ; Staining and Labeling ; Tryptases/metabolism ; Tubulin/metabolism ; }, abstract = {Angiogenesis plays a crucial role in progression of pleural malignant mesothelioma. A significantly increased incidence of pleural mesothelioma has been attributed to exposure to fluoro-edenite, a fibrous amphibole extracted from a local stone quarry. In this study, we have investigated the expression of CD68-positive macrophages, tryptase-positive mast cells and CD31 positive areas, as expression of microvascular density, in lung tissue of sheeps exposed to fluoro-edenite fibers vs controls, by immunohistochemical, morphometric and Western blot analysis. The result have evidenced a significant increase in the expression of CD68-positive macrophages, tryptase-positive mast cells as well as a significant increase in microvascular density evaluated as CD31 positive areas in lung tissue of of sheeps exposed to fluoro-edenite fibers vs controls. These data confirmed the important role played by tumor microenvironment components, including macrophages and mast cells, in favour of angiogenesis in pleural mesothelioma induced by fluoro-edenite exposure.}, } @article {pmid27325621, year = {2017}, author = {Meisenkothen, C}, title = {Malignant Mesothelioma in a Motor Vehicle Mechanic.}, journal = {New solutions : a journal of environmental and occupational health policy : NS}, volume = {26}, number = {4}, pages = {524-542}, doi = {10.1177/1048291116655526}, pmid = {27325621}, issn = {1541-3772}, mesh = {Asbestos/*adverse effects ; Humans ; Lung Neoplasms/*chemically induced ; Male ; Mesothelioma/*chemically induced ; Middle Aged ; Motor Vehicles ; *Occupational Exposure ; }, abstract = {Case reports remain an important source of data in the debate over the carcinogenic effect of asbestos-containing automotive friction products. This report documents a case of pleural mesothelioma accompanied by asbestos bodies in the lung tissue of a career auto mechanic with no other known sources of exposure. Previously unreported historical and contemporary exposure data are also discussed in the context of providing additional support for the proposition that work with asbestos-containing automotive products presents a risk of significant exposure. While there remains a body of negative epidemiology that fails to find an increased risk of disease among auto workers, those data must be approached with caution. Many of those studies have drawn technical criticisms, which are beyond the scope of this report, but they remain a key part of the legal defense mounted by defendant-companies who are involved in asbestos-related litigation. This ongoing debate provides the context for the continued relevance of case reports such as this one, as well as the presentation of new and previously unpublished exposure data.}, } @article {pmid27325080, year = {2016}, author = {Landrigan, PJ and , }, title = {Comments on the Causation of Malignant Mesothelioma: Rebutting the False Concept That Recent Exposures to Asbestos Do Not Contribute to Causation of Mesothelioma.}, journal = {Annals of global health}, volume = {82}, number = {1}, pages = {214-216}, doi = {10.1016/j.aogh.2016.01.017}, pmid = {27325080}, issn = {2214-9996}, mesh = {Asbestos/*toxicity ; Humans ; Italy ; *Mesothelioma ; Occupational Exposure/*adverse effects ; Pleural Neoplasms ; }, abstract = {BACKGROUND: European asbestos manufacturers and their expert witnesses have advanced the claim that recent exposures to asbestos are not of significance in the causation of malignant mesothelioma. They argue that in cases of prolonged exposure to asbestos only the earliest exposures contribute to mesothelioma induction.

METHODS: The Collegium Ramazzini examined this claim and compared it with the findings of the Epidemiology and Public Health Working Group of the Second Italian Consensus Conference on Pleural Mesothelioma. This independent Working Group noted that earlier exposures are more effective in inducing mesothelioma, but that subsequent exposures also contribute and cannot be excluded. They found convincing evidence to support the conclusion that mesothelioma incidence is proportional to cumulative asbestos exposure.

CONCLUSION: The Collegium Ramazzini concludes that risk of malignant mesothelioma is proportional to cumulative exposure to asbestos in which all exposures - early as well as late - contribute to the totality of risk. The Collegium Ramazzini rejects as false and scientifically unfounded the notion that only the earliest exposures to asbestos contribute to mesothelioma induction.}, } @article {pmid27325079, year = {2016}, author = {Takahashi, K and Landrigan, PJ and , }, title = {The Global Health Dimensions of Asbestos and Asbestos-Related Diseases.}, journal = {Annals of global health}, volume = {82}, number = {1}, pages = {209-213}, doi = {10.1016/j.aogh.2016.01.019}, pmid = {27325079}, issn = {2214-9996}, mesh = {Asbestos/*adverse effects ; Asbestos, Serpentine ; Asbestosis/*epidemiology/prevention & control ; Developed Countries ; Developing Countries ; *Global Health ; Humans ; International Cooperation ; Occupational Exposure/*adverse effects ; }, abstract = {The Collegium Ramazzini (CR) reaffirms its long-standing position that responsible public health action is to ban all extraction and use of asbestos, including chrysotile. This current statement updates earlier statements by the CR with a focus on global health dimensions of asbestos and asbestos-related diseases (ARDs). The ARD epidemic will likely not peak for at least a decade in most industrialized countries and for several decades in industrializing countries. Asbestos and ARDs will continue to present challenges in the arena of occupational medicine and public health, as well as in clinical research and practice, and have thus emerged as a global health issue. Industrialized countries that have already gone through the transition to an asbestos ban have learned lessons and acquired know-how and capacity that could be of great value if deployed in industrializing countries embarking on the transition. The accumulated wealth of experience and technologies in industrialized countries should thus be shared internationally through global campaigns to eliminate ARDs.}, } @article {pmid27320084, year = {2016}, author = {Cabibi, D and Tutino, R and Salamone, G and Cocorullo, G and Agrusa, A and Gulotta, G}, title = {Diffuse malignant biphasic peritoneal mesothelioma with cystic areas.}, journal = {Annali italiani di chirurgia}, volume = {87}, number = {}, pages = {}, pmid = {27320084}, issn = {2239-253X}, mesh = {Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Appendicitis/diagnosis ; Asbestos/adverse effects ; Ascites/etiology ; Biomarkers, Tumor/analysis ; Cisplatin/administration & dosage ; Crohn Disease/diagnosis ; Diagnosis, Differential ; Diagnostic Errors ; Humans ; Lung Neoplasms/diagnosis/drug therapy/etiology/*pathology ; Male ; Mesothelioma/diagnosis/drug therapy/etiology/*pathology ; Mesothelioma, Cystic/diagnosis/drug therapy/etiology/*pathology ; Mesothelioma, Malignant ; Occupational Exposure ; Pemetrexed/administration & dosage ; Peritoneal Neoplasms/diagnosis/drug therapy/etiology/*pathology ; }, abstract = {UNLABELLED: We report a case of peritoneal biphasic mesothelioma with cystic areas in a patient with professional exposure to asbestos. It showed focal epithelial glandular and papillary proliferations, also presenting fluid filled cysts, whose wall consisted of a proliferation of spindle cells. Atypia and mitoses were very scanty. EMA, vimentin, CK5/6, D2-40, calretinin and P53 were positive and desmin was negative in both epithelial and spindle areas, including the ones surrounding the cystic spaces. These findings gave an essential aid in the differential diagnosis with a benign cystic mesothelioma and with a cystic epithelial mesothelioma with secondary pseudosarcomatous myofibroblastic proliferation. The presence of cystic areas in a malignant mesothelioma could make difficult the diagnosis. A large amount of tumour tissue is necessary for confirming the biphasic histotype, an aggressive histotype, even in the presence of mild histological features and of some others favourable clinical prognostic indices as in this case. To our knowledge this is the first case of malignant peritoneal biphasic mesothelioma with cystic features reported in the literature.

KEY WORDS: Cystic Mesothelioma, Immunohistochemistry, Malignant Mesothelioma, Peritoneal Diseases, Mesothelial Neoplasms.}, } @article {pmid27318362, year = {2016}, author = {Webb, J and Yiu, YW and Giastefani, S and Carr-White, G}, title = {Pericardial mesothelioma.}, journal = {QJM : monthly journal of the Association of Physicians}, volume = {109}, number = {9}, pages = {631-632}, doi = {10.1093/qjmed/hcw099}, pmid = {27318362}, issn = {1460-2393}, mesh = {Aged ; Asbestos/*adverse effects ; Echocardiography/methods ; Fatal Outcome ; *Heart Neoplasms/etiology/pathology/physiopathology ; Humans ; Magnetic Resonance Imaging, Cine/methods ; Male ; *Mesothelioma/etiology/pathology/physiopathology ; *Pericardium/diagnostic imaging/pathology ; *Pleural Neoplasms/etiology/pathology/physiopathology ; Radiography, Thoracic/methods ; }, } @article {pmid27312399, year = {2016}, author = {Mensi, C and De Matteis, S and Dallari, B and Riboldi, L and Bertazzi, PA and Consonni, D}, title = {Incidence of mesothelioma in Lombardy, Italy: exposure to asbestos, time patterns and future projections.}, journal = {Occupational and environmental medicine}, volume = {73}, number = {9}, pages = {607-613}, pmid = {27312399}, issn = {1470-7926}, mesh = {Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Environmental Exposure/adverse effects ; Female ; Humans ; Incidence ; Interviews as Topic ; Italy/epidemiology ; Lung Neoplasms/*chemically induced/*epidemiology ; Male ; Mesothelioma/*chemically induced/*epidemiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Diseases/*chemically induced/*epidemiology ; Occupational Exposure/*adverse effects ; Poisson Distribution ; Registries ; Risk Factors ; Sex Distribution ; Time Factors ; Young Adult ; }, abstract = {OBJECTIVES: In Italy, asbestos has been extensively used from 1945 to 1992. We evaluated the impact of exposure to asbestos on occurrence of malignant mesothelioma (MM) in the Lombardy Region, Northwest Italy, the most populated and industrialised Italian region.

METHODS: From the Lombardy Mesothelioma Registry, we selected all incident cases of MM diagnosed between 2000 and 2012. We described sources of exposure to asbestos and examined time trends of MM rates. Using Poisson age-cohort models, we derived projections of burden of MM in the Lombardy population for the period 2013-2029.

RESULTS: In 2000-2012, we recorded 4442 cases of MM (2850 men, 1592 women). Occupational exposure to asbestos was more frequent in men (73.6%) than in women (38.2%). Non-occupational exposure was found for 13.6% of women and 3.6% of men. The average number of cases of MM per year was still increasing (+3.6% in men, +3.3% in women). Incidence rates were still increasing in individuals aged 65+ years and declining in younger people. A maximum of 417 cases of MM (267 men, 150 women) are expected in 2019. We forecast there will be 6832 more cases (4397 in men, 2435 in women) in the period 2013-2029, for a total of 11 274 cases of MM (7247 in men, 4027 in women) in 30 years.

CONCLUSIONS: This study documented a high burden of MM in both genders in the Lombardy Region, reflecting extensive occupational (mainly in men) and non-occupational (mainly in women) exposure to asbestos in the past. Incidence rates are still increasing; a downturn in occurrence of MM is expected to occur after 2019.}, } @article {pmid27302977, year = {2016}, author = {Yang, HY and Huang, SH and Shie, RH and Chen, PC}, title = {Cancer mortality in a population exposed to nephrite processing.}, journal = {Occupational and environmental medicine}, volume = {73}, number = {8}, pages = {528-536}, doi = {10.1136/oemed-2016-103586}, pmid = {27302977}, issn = {1470-7926}, mesh = {Adult ; Asbestos/*adverse effects ; Asbestos, Amphibole ; Carcinogens ; Cohort Studies ; Esophageal Neoplasms/*mortality ; Female ; Humans ; Hypopharyngeal Neoplasms/*mortality ; Laryngeal Neoplasms/*mortality ; Male ; Manufacturing Industry ; Mesothelioma/mortality ; Minerals ; Occupational Diseases/*mortality ; Occupational Exposure/*adverse effects ; Particle Size ; Particulate Matter/adverse effects ; Risk Factors ; Stomach Neoplasms/*mortality ; }, abstract = {OBJECTIVES: Although asbestos has been recognised as a strong carcinogen, many asbestos minerals exist in concrete masses, and the health risks of these materials remain inconclusive. Nephrite jade is a concrete mass of amphibole that consists of asbestiform and non-asbestiform particles. The objective of the study was to explore the carcinogenetic effect of nephrite.

METHODS: We examined cancer mortality between 1979 and 2011 in Fengtian, where nephrite was mass produced from 1970 to 1980, and calculated standardised mortality ratios (SMRs).

RESULTS: We observed significantly elevated mortality risks for cancer of the hypopharynx (SMR 2.31; 95% CI 1.37 to 3.65), larynx (SMR 2.51; 95% CI 1.55 to 3.83), oesophagus (SMR 2.04; 95% CI 1.62 to 2.54) and stomach (SMR 1.38; 95% CI 1.17 to 1.63). This study analysed the lengths, widths, structures, chemical compositions, aerodynamic diameters and distributions of elongated mineral particles (EMPs) in airways. The majority of the EMPs (68%) were short (<5 μm) and thin (<0.5 µm), and possessed asbestiform structures. The median aerodynamic diameter of the EMPs was 1.2 μm. The total deposition proportion in airways was 51.3%. The major deposition sites were the head airway (37.5%), followed by the alveolar region (10.6%) and the tracheobronchial region (3.2%).

CONCLUSIONS: The results have shown an association between EMPs and increased risk of respiratory and digestive cancers. Further research is needed that includes information on smoking habits and exposure to asbestos.}, } @article {pmid27300447, year = {2016}, author = {Pessôa, FM and de Melo, AS and Souza, AS and de Souza, LS and Hochhegger, B and Zanetti, G and Marchiori, E}, title = {Applications of Magnetic Resonance Imaging of the Thorax in Pleural Diseases: A State-of-the-Art Review.}, journal = {Lung}, volume = {194}, number = {4}, pages = {501-509}, pmid = {27300447}, issn = {1432-1750}, mesh = {Empyema/diagnostic imaging ; Endometriosis/diagnostic imaging ; Female ; Fibroma/*diagnostic imaging ; Foreign Bodies/diagnostic imaging ; Humans ; Lymphoma/diagnostic imaging ; Magnetic Resonance Imaging/*methods ; Male ; Mesothelioma/*diagnostic imaging ; Pleural Effusion/diagnostic imaging ; Pleural Neoplasms/*diagnostic imaging ; Splenosis/diagnostic imaging ; Thorax/diagnostic imaging ; }, abstract = {The aim of this review was to present the main aspects of pleural diseases seen with conventional and advanced magnetic resonance imaging (MRI) techniques. This modality is considered to be the gold standard for the evaluation of the pleural interface, characterization of complex pleural effusion, and identification of exudate and hemorrhage, as well as in the analysis of superior sulcus tumors, as it enables more accurate staging. The indication for MRI of the thorax in the identification of these conditions is increasing in comparison to computerized tomography, and it can also be used to support the diagnosis of pulmonary illnesses. This literature review describes the morphological and functional aspects of the main benign and malignant pleural diseases assessed with MRI, including mesothelioma, metastasis, lymphoma, fibroma, lipoma, endometriosis, asbestos-related pleural disease, empyema, textiloma, and splenosis.}, } @article {pmid27298458, year = {2016}, author = {Ferrante, D and Mirabelli, D and Tunesi, S and Terracini, B and Magnani, C}, title = {Authors's response: Pleural mesothelioma and occupational and non-occupational asbestos exposure: a case-control study with quantitative risk assessment.}, journal = {Occupational and environmental medicine}, volume = {73}, number = {10}, pages = {713-714}, doi = {10.1136/oemed-2016-103851}, pmid = {27298458}, issn = {1470-7926}, mesh = {*Asbestos ; Case-Control Studies ; Humans ; Mesothelioma ; Occupational Exposure ; *Pleural Neoplasms ; Risk Assessment ; }, } @article {pmid27293862, year = {2016}, author = {Kim, KC and Vo, HP}, title = {Localized malignant pleural sarcomatoid mesothelioma misdiagnosed as benign localized fibrous tumor.}, journal = {Journal of thoracic disease}, volume = {8}, number = {6}, pages = {E379-84}, pmid = {27293862}, issn = {2072-1439}, abstract = {Localized malignant pleural mesothelioma (LMPM) is a rare tumor with good prognosis by surgical resection. We report an atypical case of malignant pleural sarcomatoid mesothelioma (SM) in an asymptomatic 65-year-old woman, who had no history of exposure to asbestos. She presented with a small pleural mass without pleural effusion and was misdiagnosed as a benign localized fibrous tumor (BLFT) on pathologic examination through a surgical tumor specimen. However, seven months later, the patient returned with serious cancerous symptoms. A large recurrent tumor mass was found within the chest wall invading at the old surgical resection site. SM, a subtype of LMPM, was confirmed with histopathogy and immunohistochemisty. In conclusion, malignant pleural mesothelioma (MPM) can present with typical radiologic finding similar to a BLFT, and has a wide histopathologic presentation in biopsy specimen. A thorough pathologic investigation should be attempted even when a pleural mass resembles benign, localized, and small on radiologic studies.}, } @article {pmid27290892, year = {2016}, author = {Ruff, K and Mirabelli, D and Magnani, C}, title = {Scientific journal publishes second eratum regarding false information by scientists funded by asbestos interests.}, journal = {Epidemiologia e prevenzione}, volume = {40}, number = {2}, pages = {138-139}, doi = {10.19191/EP16.2.P138.069}, pmid = {27290892}, issn = {1120-9763}, abstract = {In a paper published on Epidemiology, Biostatistics and Public Health, Ilgren et al. claimed that cases of mesothelioma among workers of the Balangero (a municipality of the province of Turin, Northern Italy) chrysotile mine and nearby residents were not caused by chrysotile, but by other forms of asbestos. In support, they cited a reference where no pertaining evidence can be found. One year after the paper, an erratum was published by the journal editors in chief, warning that an erroneous citation was present. The erratum is weak and misleading, concealing the fact that a false statement was supported by such error and that it may serve the interests of the chrysotile industry, by dismissing evidence of chrysotile carcinogenicity. Some of the article authors, of the editors in chief and members of the journal editorial board had financial ties to asbestos interests.}, } @article {pmid27288871, year = {2016}, author = {Hoda, MA and Dong, Y and Rozsas, A and Klikovits, T and Laszlo, V and Ghanim, B and Stockhammer, P and Ozsvar, J and Jakopovic, M and Samarzija, M and Brcic, L and Bendek, M and Szirtes, I and Reid, G and Kirschner, MB and Kao, SC and Opitz, I and Weder, W and Frauenfelder, T and Nguyen-Kim, TD and Aigner, C and Klepetko, W and van Zandwijk, N and Berger, W and Dome, B and Grusch, M and Hegedus, B}, title = {Circulating activin A is a novel prognostic biomarker in malignant pleural mesothelioma - A multi-institutional study.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {63}, number = {}, pages = {64-73}, doi = {10.1016/j.ejca.2016.04.018}, pmid = {27288871}, issn = {1879-0852}, mesh = {Activins/*blood ; Aged ; Biomarkers, Tumor/*blood ; Enzyme-Linked Immunosorbent Assay ; Female ; Fibrinogen/analysis ; Humans ; Lung Neoplasms/*blood/pathology ; Male ; Mesothelioma/*blood/pathology ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/*blood/pathology ; Prognosis ; }, abstract = {INTRODUCTION: The deregulation of activin expression is often observed in various malignancies. Previous studies indicate that activin A plays a protumourigenic role in malignant pleural mesothelioma (MPM). The aim of the study was to evaluate circulating activin A level as a biomarker in MPM.

METHODS: Plasma samples were collected from 129 MPM patients in four institutions at the time of diagnosis or before surgical resection. Samples from 45 healthy individuals and from 16 patients with non-malignant pleural diseases served as controls. Circulating activin A was measured by enzyme-linked immunosorbent assay and correlated to clinicopathological variables.

RESULTS: Plasma activin A level was significantly elevated in MPM patients (862 ± 83 pg/ml) when compared to healthy controls (391 ± 21 pg/ml; P < 0.0001). Patients with pleuritis or fibrosis only showed a modest increase (versus controls; 625 ± 95 pg/ml; P = 0.0067). Sarcomatoid (n = 10, 1629 ± 202 pg/ml, P = 0.0019) and biphasic (n = 23, 1164 ± 233 pg/ml, P = 0.0188) morphology were associated with high activin A levels when compared to epithelioid histology (n = 94, 712 ± 75 pg/ml). The tumour volume showed a positive correlation with increased circulating activin A levels. MPM patients with below median activin A levels had a significantly longer overall survival when compared to those with high activin A levels (median survival 735 versus 365 d, P < 0.0001). Importantly, circulating activin A levels were exclusively prognostic in epithelioid MPM.

CONCLUSIONS: Our findings suggest that the measurement of circulating activin A may support the histological classification of MPM and at the same time help to identify epithelioid MPM patients with poor prognosis.}, } @article {pmid27287512, year = {2016}, author = {Kuryk, L and Haavisto, E and Garofalo, M and Capasso, C and Hirvinen, M and Pesonen, S and Ranki, T and Vassilev, L and Cerullo, V}, title = {Synergistic anti-tumor efficacy of immunogenic adenovirus ONCOS-102 (Ad5/3-D24-GM-CSF) and standard of care chemotherapy in preclinical mesothelioma model.}, journal = {International journal of cancer}, volume = {139}, number = {8}, pages = {1883-1893}, doi = {10.1002/ijc.30228}, pmid = {27287512}, issn = {1097-0215}, mesh = {Adenoviridae/genetics/immunology/physiology ; Animals ; Antineoplastic Combined Chemotherapy Protocols/*pharmacology ; Carboplatin/administration & dosage ; Cell Line, Tumor ; Combined Modality Therapy ; Granulocyte-Macrophage Colony-Stimulating Factor/administration & dosage/genetics/immunology ; Humans ; Lung Neoplasms/drug therapy/immunology/*therapy/virology ; Mesothelioma/drug therapy/immunology/*therapy/virology ; Mesothelioma, Malignant ; Mice ; Mice, Inbred BALB C ; Oncolytic Virotherapy/*methods ; Pemetrexed/administration & dosage ; Virus Replication ; Xenograft Model Antitumor Assays ; }, abstract = {Malignant mesothelioma (MM) is a rare cancer type caused mainly by asbestos exposure. The median overall survival time of a mesothelioma cancer patient is less than 1-year from diagnosis. Currently there are no curative treatment modalities for malignant mesothelioma, however treatments such as surgery, chemotherapy and radiotherapy can help to improve patient prognosis and increase life expectancy. Pemetrexed-Cisplatin is the only standard of care (SoC) chemotherapy for malignant mesothelioma, but the median PFS/OS (progression-free survival/overall survival) from the initiation of treatment is only up to 12 months. Therefore, new treatment strategies against malignant mesothelioma are in high demand. ONCOS-102 is a dual targeting, chimeric oncolytic adenovirus, coding for human GM-CSF. The safety and immune activating properties of ONCOS-102 have already been assessed in phase 1 study (NCT01598129). In this preclinical study, we evaluated the antineoplastic activity of combination treatment with SoC chemotherapy (Pemetrexed, Cisplatin, Carboplatin) and ONCOS-102 in xenograft BALB/c model of human malignant mesothelioma. We demonstrated that ONCOS-102 is able to induce immunogenic cell death of human mesothelioma cell lines in vitro and showed anti-tumor activity in the treatment of refractory H226 malignant pleural mesothelioma (MPM) xenograft model. While chemotherapy alone showed no anti-tumor activity in the mesothelioma mouse model, ONCOS-102 was able to slow down tumor growth. Interestingly, a synergistic anti-tumor effect was seen when ONCOS-102 was combined with chemotherapy regimens. These findings give a rationale for the clinical testing of ONCOS-102 in combination with first-line chemotherapy in patients suffering from malignant mesothelioma.}, } @article {pmid27286698, year = {2016}, author = {Novello, S and Pinto, C and Torri, V and Porcu, L and Di Maio, M and Tiseo, M and Ceresoli, G and Magnani, C and Silvestri, S and Veltri, A and Papotti, M and Rossi, G and Ricardi, U and Trodella, L and Rea, F and Facciolo, F and Granieri, A and Zagonel, V and Scagliotti, G}, title = {The Third Italian Consensus Conference for Malignant Pleural Mesothelioma: State of the art and recommendations.}, journal = {Critical reviews in oncology/hematology}, volume = {104}, number = {}, pages = {9-20}, doi = {10.1016/j.critrevonc.2016.05.004}, pmid = {27286698}, issn = {1879-0461}, mesh = {Animals ; Humans ; Incidence ; Italy/epidemiology ; *Lung Neoplasms/complications/diagnosis/epidemiology/therapy ; *Mesothelioma/complications/diagnosis/epidemiology/therapy ; Mesothelioma, Malignant ; Pleural Effusion/etiology ; *Pleural Neoplasms/complications/diagnosis/epidemiology/therapy ; Public Health ; Risk Factors ; }, abstract = {Malignant Pleural Mesothelioma (MPM) remains a relevant public health issue, and asbestos exposure is the most relevant risk factor. The incidence has considerably and constantly increased over the past two decades in the industrialized countries and is expected to peak in 2020-2025. In Italy, a standardized-rate incidence in 2011 among men was 3.5 and 1.25 per 100,000 in men and women, respectively, and wide differences are noted among different geographic areas. The disease remains challenging in terms of diagnosis, staging and treatment and an optimal strategy has not yet been clearly defined. The Third Italian Multidisciplinary Consensus Conference on Malignant Pleural Mesothelioma was held in Bari (Italy) in January 30-31, 2015. This Consensus has provided updated recommendations on the MPM management for health institutions, clinicians and patients.}, } @article {pmid27282309, year = {2016}, author = {Hylebos, M and Van Camp, G and van Meerbeeck, JP and Op de Beeck, K}, title = {The Genetic Landscape of Malignant Pleural Mesothelioma: Results from Massively Parallel Sequencing.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {11}, number = {10}, pages = {1615-1626}, doi = {10.1016/j.jtho.2016.05.020}, pmid = {27282309}, issn = {1556-1380}, mesh = {Exome ; Genome/*genetics ; Humans ; Lung Neoplasms/pathology ; Mesothelioma/pathology ; Mesothelioma, Malignant ; Pleural Neoplasms/pathology ; Transcriptome ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare yet aggressive tumor that is causally associated with-mostly professional-asbestos exposure. Given the long latency between exposure and disease, and because asbestos is still being used, MPM will remain a global health issue for decades to come. Notwithstanding the increasing incidence of MPM and the fact that patients with MPM face a poor prognosis, currently available treatment options are limited. To enable the development of novel targeted therapies, identification of the genetic alterations underlying MPM will be crucial. The first studies reporting on the genomic background of MPM identified recurrent somatic mutations in a number of tumor suppressor genes (i.e., cyclin-dependent kinase inhibitor 2A gene [CDKN2A], neurofibromin 2 (merlin) gene [NF2], and BRCA1 associated protein 1 gene [BAP1]). More recently, massively parallel sequencing strategies have been used and have provided a more genome-wide view on the genetic landscape of MPM. This review summarizes their results, describing alterations that cluster mainly in four pathways: the tumor protein p53/DNA repair, cell cycle, mitogen-activated protein kinase, and phosphoinisitide 3-kinase (PI3K)/AKT pathways. As these pathways are important during tumor development, they provide interesting candidates for targeting with novel drugs.}, } @article {pmid27281118, year = {2016}, author = {de Ridder, GG and Kraynie, A and Pavlisko, EN and Oury, TD and Roggli, VL}, title = {Asbestos content of lung tissue in patients with malignant peritoneal mesothelioma: A study of 42 cases.}, journal = {Ultrastructural pathology}, volume = {40}, number = {3}, pages = {134-141}, doi = {10.3109/01913123.2016.1170085}, pmid = {27281118}, issn = {1521-0758}, mesh = {Adult ; Aged ; Asbestosis/*complications/*epidemiology ; Female ; Humans ; Lung Neoplasms/*complications/pathology ; Male ; Mesothelioma/*complications/pathology ; Mesothelioma, Malignant ; Microscopy, Electron, Scanning ; Middle Aged ; Peritoneal Neoplasms/*complications/pathology ; Spectrometry, X-Ray Emission ; }, abstract = {Lung tissue from 42 peritoneal mesothelioma cases was analyzed by light microscopy and scanning electron microscopy/energy dispersive spectrometry. There were 34 men and 8 women with a mean age of 61 ± 10 years. Also, 17% of cases had histologically confirmed asbestosis, and 26% had only parietal pleural plaques. The asbestos body count exceeded our normal range in 22 of 42 cases (52%). Cases with asbestos-related pulmonary disease had higher fiber burdens than those without. The vast majority of fibers were commercial amphiboles (amosite with lesser amounts of crocidolite). These findings concur with previously published epidemiological observations.}, } @article {pmid27279560, year = {2016}, author = {Kato, T and Lee, D and Wu, L and Patel, P and Young, AJ and Wada, H and Hu, HP and Ujiie, H and Kaji, M and Kano, S and Matsuge, S and Domen, H and Kaga, K and Matsui, Y and Kanno, H and Hatanaka, Y and Hatanaka, KC and Matsuno, Y and de Perrot, M and Yasufuku, K}, title = {Kinesin family members KIF11 and KIF23 as potential therapeutic targets in malignant pleural mesothelioma.}, journal = {International journal of oncology}, volume = {49}, number = {2}, pages = {448-456}, doi = {10.3892/ijo.2016.3566}, pmid = {27279560}, issn = {1791-2423}, mesh = {Adult ; Aged ; Aged, 80 and over ; Cell Line, Tumor ; Female ; Gene Knockdown Techniques ; Humans ; Kinesins/biosynthesis/*genetics ; Male ; Mesothelioma/*genetics/metabolism/pathology/*therapy ; Microtubule-Associated Proteins/biosynthesis/*genetics ; Middle Aged ; Molecular Targeted Therapy ; Pleural Neoplasms/*genetics/metabolism/pathology/*therapy ; RNA, Small Interfering/administration & dosage/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Tissue Array Analysis ; Transfection ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare and aggressive form of cancer commonly associated with asbestos exposure that stems from the thoracic mesothelium with high mortality rate. Currently, treatment options for MPM are limited, and new molecular targets for treatments are urgently needed. Using quantitative reverse transcription-polymerase chain reaction (RT-PCR) and an RNA interference-based screening, we screened two kinesin family members as potential therapeutic targets for MPM. Following in vitro investigation of the target silencing effects on MPM cells, a total of 53 MPMs were analyzed immunohistochemically with tissue microarray. KIF11 and KIF23 transcripts were found to be overexpressed in the majority of clinical MPM samples as well as human MPM cell lines as determined by quantitative RT-PCR. Gene knockdown in MPM cell lines identified growth inhibition following knockdown of KIF11 and KIF23. High expression of KIF11 (KIF11-H) and KIF23 (KIF23-H) were found in 43.4 and 50.9% of all the MPM cases, respectively. Patients who received curative resection with tumors displaying KIF23-H showed shorter overall survival (P=0.0194). These results provide that inhibition of KIF11 and KIF23 may hold promise for treatment of MPMs, raising the possibility that kinesin-based drug targets may be developed in the future.}, } @article {pmid27259231, year = {2016}, author = {Micolucci, L and Akhtar, MM and Olivieri, F and Rippo, MR and Procopio, AD}, title = {Diagnostic value of microRNAs in asbestos exposure and malignant mesothelioma: systematic review and qualitative meta-analysis.}, journal = {Oncotarget}, volume = {7}, number = {36}, pages = {58606-58637}, pmid = {27259231}, issn = {1949-2553}, mesh = {Asbestos/*toxicity ; Biomarkers, Tumor ; Computational Biology ; Epigenesis, Genetic ; GPI-Linked Proteins/genetics ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/*chemically induced/*diagnosis/genetics ; Mesothelin ; Mesothelioma/*chemically induced/*diagnosis/genetics ; Mesothelioma, Malignant ; MicroRNAs/blood/*genetics ; Oligonucleotide Array Sequence Analysis ; Phenotype ; Tissue Array Analysis ; Tissue Distribution ; }, abstract = {BACKGROUND: Asbestos is a harmful and exceptionally persistent natural material. Malignant mesothelioma (MM), an asbestos-related disease, is an insidious, lethal cancer that is poorly responsive to current treatments. Minimally invasive, specific, and sensitive biomarkers providing early and effective diagnosis in high-risk patients are urgently needed. MicroRNAs (miRNAs, miRs) are endogenous, non-coding, small RNAs with established diagnostic value in cancer and pollution exposure. A systematic review and a qualitative meta-analysis were conducted to identify high-confidence miRNAs that can serve as biomarkers of asbestos exposure and MM.

METHODS: The major biomedical databases were systematically searched for miRNA expression signatures related to asbestos exposure and MM. The qualitative meta-analysis applied a novel vote-counting method that takes into account multiple parameters. The most significant miRNAs thus identified were then subjected to functional and bioinformatic analysis to assess their biomarker potential.

RESULTS: A pool of deregulated circulating and tissue miRNAs with biomarker potential for MM was identified and designated as "mesomiRs" (MM-associated miRNAs). Comparison of data from asbestos-exposed and MM subjects found that the most promising candidates for a multimarker signature were circulating miR-126-3p, miR-103a-3p, and miR-625-3p in combination with mesothelin. The most consistently described tissue miRNAs, miR-16-5p, miR-126-3p, miR-143-3p, miR-145-5p, miR-192-5p, miR-193a-3p, miR-200b-3p, miR-203a-3p, and miR-652-3p, were also found to provide a diagnostic signature and should be further investigated as possible therapeutic targets.

CONCLUSION: The qualitative meta-analysis and functional investigation confirmed the early diagnostic value of two miRNA signatures for MM. Large-scale, standardized validation studies are needed to assess their clinical relevance, so as to move from the workbench to the clinic.}, } @article {pmid27245839, year = {2016}, author = {Cheng, YY and Wright, CM and Kirschner, MB and Williams, M and Sarun, KH and Sytnyk, V and Leshchynska, I and Edelman, JJ and Vallely, MP and McCaughan, BC and Klebe, S and van Zandwijk, N and Lin, RC and Reid, G}, title = {KCa1.1, a calcium-activated potassium channel subunit alpha 1, is targeted by miR-17-5p and modulates cell migration in malignant pleural mesothelioma.}, journal = {Molecular cancer}, volume = {15}, number = {1}, pages = {44}, pmid = {27245839}, issn = {1476-4598}, mesh = {3' Untranslated Regions ; Binding Sites ; Cell Line, Tumor ; Cell Movement ; Databases, Genetic ; Gene Expression Profiling/*methods ; Gene Expression Regulation, Neoplastic ; Humans ; Large-Conductance Calcium-Activated Potassium Channel alpha Subunits/*genetics/metabolism ; Lung Neoplasms/*genetics ; Mesothelioma/*genetics ; Mesothelioma, Malignant ; MicroRNAs/*genetics ; Oligonucleotide Array Sequence Analysis/*methods ; Pleural Neoplasms/*genetics ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive, locally invasive, cancer elicited by asbestos exposure and almost invariably a fatal diagnosis. To date, we are one of the leading laboratory that compared microRNA expression profiles in MPM and normal mesothelium samples in order to identify dysregulated microRNAs with functional roles in mesothelioma. We interrogated a significant collection of MPM tumors and normal pleural samples in our biobank in search for novel therapeutic targets.

METHODS: Utilizing mRNA-microRNA correlations based on differential gene expression using Gene Set Enrichment Analysis (GSEA), we systematically combined publicly available gene expression datasets with our own MPM data in order to identify candidate targets for MPM therapy.

RESULTS: We identified enrichment of target binding sites for the miR-17 and miR-30 families in both MPM tumors and cell lines. RT-qPCR revealed that members of both families were significantly downregulated in MPM tumors and cell lines. Interestingly, lower expression of miR-17-5p (P = 0.022) and miR-20a-5p (P = 0.026) was clearly associated with epithelioid histology. We interrogated the predicted targets of these differentially expressed microRNA families in MPM cell lines, and identified KCa1.1, a calcium-activated potassium channel subunit alpha 1 encoded by the KCNMA1 gene, as a target of miR-17-5p. KCa1.1 was overexpressed in MPM cells compared to the (normal) mesothelial line MeT-5A, and was also upregulated in patient tumor samples compared to normal mesothelium. Transfection of MPM cells with a miR-17-5p mimic or KCNMA1-specific siRNAs reduced mRNA expression of KCa1.1 and inhibited MPM cell migration. Similarly, treatment with paxilline, a small molecule inhibitor of KCa1.1, resulted in suppression of MPM cell migration.

CONCLUSION: These functional data implicating KCa1.1 in MPM cell migration support our integrative approach using MPM gene expression datasets to identify novel and potentially druggable targets.}, } @article {pmid27245376, year = {2016}, author = {Martínez-Miranda, MD and Nielsen, B and Nielsen, JP}, title = {Simple benchmark for mesothelioma projection for Great Britain.}, journal = {Occupational and environmental medicine}, volume = {73}, number = {8}, pages = {561-563}, doi = {10.1136/oemed-2015-103303}, pmid = {27245376}, issn = {1470-7926}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Cohort Studies ; Female ; Forecasting ; Humans ; Male ; Mesothelioma/*mortality ; Middle Aged ; Occupational Diseases/mortality ; Occupational Exposure/adverse effects ; United Kingdom/epidemiology ; Young Adult ; }, abstract = {BACKGROUND: It is of considerable interest to forecast the future burden of mesothelioma mortality. Data on deaths are available, whereas no measure of asbestos exposure is available.

METHODS: We compare two Poisson models: a response-only model with an age-cohort specification and a multinomial model with epidemiologically motivated frequencies.

RESULTS: The response-only model has 5% higher peak mortality than the dose-response model. The former performs slightly better in out-of-sample comparison.

CONCLUSIONS: Mortality is predicted to peak at about 2100 deaths around 2017 among males in cohorts until 1966 and below 90 years of age. The response-only model is a simple benchmark that forecasts just as well as more complicated models.}, } @article {pmid27240221, year = {2016}, author = {Candura, SM and Boeri, R and Teragni, C and Chen, Y and Scafa, F}, title = {Renal cell carcinoma and malignant peritoneal mesothelioma after occupational asbestos exposure: case report.}, journal = {La Medicina del lavoro}, volume = {107}, number = {3}, pages = {172-177}, pmid = {27240221}, issn = {0025-7818}, mesh = {Aged ; Asbestos/*adverse effects ; Carcinoma, Renal Cell/*etiology ; Humans ; Kidney Neoplasms/*etiology ; Male ; Mesothelioma/*etiology ; Neoplasms, Multiple Primary/*etiology ; Occupational Diseases/*etiology ; Occupational Exposure/*adverse effects ; Peritoneal Neoplasms/*etiology ; }, abstract = {UNLABELLED: Asbestos is the main causal factor for malignant mesothelioma (MM), a relatively rare and aggressive malignancy. Some epidemiological evidence suggests a role of this agent also in the etiology of renal cell carcinoma (RCC), the most common form of kidney cancer.

CASE REPORT: After 7 years of asbestos exposure, a 76-year-old asbestos-cement worker came to our notice with left flank pain. Diagnostic imaging disclosed a neoplasm in the upper two thirds of the left kidney, without evidence of metastases. After surgery (nephrectomy with para-aortic lymphadenectomy), histopathology revealed clear cell RCC. One year later, the patient was hospitalized for abdominal pain. Laparoscopy showed diffuse neoplastic infiltration of the peritoneum and liver. Histological and immunohistochemical examination of the bioptic samples led to the diagnosis of biphasic MM. The subject died 2 months later. Autopsy disclosed ascites and diffuse infiltration of the abdominal wall and viscera, without evidence of RCC relapse.

CONCLUSIONS: This is the second reported case of association between RCC and peritoneal MM in the scientific literature. Asbestos might be involved in the causation of both malignancies.}, } @article {pmid27236568, year = {2016}, author = {Ledda, C and Pomara, C and Bracci, M and Mangano, D and Ricceri, V and Musumeci, A and Ferrante, M and Musumeci, G and Loreto, C and Fenga, C and Santarelli, L and Rapisarda, V}, title = {Natural carcinogenic fiber and pleural plaques assessment in a general population: A cross-sectional study.}, journal = {Environmental research}, volume = {150}, number = {}, pages = {23-29}, doi = {10.1016/j.envres.2016.05.024}, pmid = {27236568}, issn = {1096-0953}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asbestos, Amphibole/*toxicity ; Carcinogens/*toxicity ; Cross-Sectional Studies ; *Environmental Exposure ; Environmental Pollutants/*toxicity ; Female ; Humans ; Lung Diseases/chemically induced/*epidemiology/pathology ; Male ; Middle Aged ; Parenchymal Tissue/drug effects ; Retrospective Studies ; Sicily/epidemiology ; Tomography, X-Ray Computed ; Young Adult ; }, abstract = {Natural carcinogenic fibers are asbestos and asbestiform fibers present as a natural component of soils or rocks. These fibers are released into the environment resulting in exposure of the general population. Environmental contamination by fibers are those cases occurred in: rural regions of Turkey, in Mediterranean countries and in other sites of the world, including northern Europe, USA and China. Fluoro-edenite(FE) is a natural mineral species first isolated in Biancavilla, Sicily. The fibers are similar in size and morphology to some amphibolic asbestos fibers, whose inhalation can cause chronic inflammation and cancer. The aim of the current study is to assess the presence and features of pleural plaques (PPs) in Biancavilla's general population exposed to FE through a retrospective cross-sectional study. All High-Resolution Computed Tomography (HRCT) chest scans carried out between June 2009 and June 2015 in Biancavilla municipality hospital site (exposed subjects) were reviewed. The exposed groups were 1:1 subjects, matched according to age and sex distributions, with unexposed subjects (n.1.240) randomly selected among HRCT chest scans carried out in a Hospital 30km away from Biancavilla. Subjects from Biancavilla with PPs were significantly more numerous than the control group ones (218 vs 38). Average age of either group was >60 years; the age of exposed subjects was significantly (p=0.0312) lesser than the unexposed group. In exposed subjects, in most PPs thickness ranged between 2 and 4.9cm(38%, n=83); while in unexposed ones PPs thickness was less than 2cm (55%, n=21). As to the size of PPs in exposed subjects, in most cases it ranged between 1cm and 24% of chest wall (53%, n=116); while in unexposed ones the size of PPs was lesser than 1cm (23%, n=58). Among exposed subjects, 36 cases (17%) PPs were detected with calcification, whereas in unexposed ones only three (8%) presented calcification. 137 lung parenchymal abnormalities were observed in exposed group; whereas, 12 lung parenchymal involvement were registered in unexposed subjects. The RR for PPs is 6,74 CI 95% (4,47-9,58) p<0,0001 in the exposed population. These findings, suggested the urge to extend the screening on the possible involvement of the respiratory tract to all Biancavilla's population, particularly in those aged more than 30. Besides, it seems essential to start indoor monitoring Biancavilla's municipality.}, } @article {pmid27220441, year = {2016}, author = {Song, PP and Wang, Y and Sun, JL and Gao, Y and Liu, J and Chen, YX}, title = {[The incidence of asbestos-related diseases about on asbestos enterprises in Qingdao from 1988 to 2014].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {34}, number = {3}, pages = {203-205}, doi = {10.3760/cma.j.issn.1001-9391.2016.03.010}, pmid = {27220441}, issn = {1001-9391}, mesh = {Asbestos ; *Asbestosis ; Dust ; Female ; Humans ; Incidence ; Lung Neoplasms ; Male ; Mesothelioma ; Occupational Exposure ; Pleural Diseases ; Workplace ; }, abstract = {OBJECTIVE: It can provide statistics reference for the prevention and treatment by analysising the status and characteristics related to the asbestos disease of an asbestos products enterprises from 1988 to 2014.

METHODS: We have collected the data concerning the case of asbestos-related disease between 1988 and 2014, then the data were arranged, collecteted and analyzed using statistical method.

RESULTS: The total of patients is 625 (male: 225, female: 400). Diagnosis of asbestosis is 617 cases, Accordingly, stage Ⅰis 500, stage Ⅱis 112 and stage Ⅲ is 5. Average age of morbidity is 64.84±9.87 and working age is 24.45±7.40 years; The patients of lung cancer caused by asbestos are 12 people, and average age of morbidity is 66.25±11.20 years, and the working age is 29.18±7.77years; The patients of mesothelioma are 4 people, average age of morbidity is 49-78 (M=60) and working age is 27years. Asbestosis patients with complications of pleural plaque is 37.44%, complications of pulmonary tuberculosis is 5.19%., and there are 239 patients lose their lives, motality is 38.74%.

CONCLUSION: There is a high incidence of a disease about asbestos related disease in the asbestos products factory, it has close relationship with asbestos exposure time, the dust concentration of workplace and type of work et al. Asbestos related diseases are still the main problem in Qingdao.}, } @article {pmid27219104, year = {2016}, author = {Egilman, D and Tran, T}, title = {A commentary on Roggli's "The So-Called Short-Fiber Controversy".}, journal = {International journal of occupational and environmental health}, volume = {22}, number = {3}, pages = {181-186}, pmid = {27219104}, issn = {2049-3967}, mesh = {Asbestos ; *Asbestos, Serpentine ; Carcinogens ; Humans ; Lung Neoplasms ; *Mesothelioma ; }, abstract = {Dr. Victor Roggli republished a "literature review and critical analysis" of the toxicity of short fiber asbestos. His paper was originally prepared and presented at a conference of asbestos defense lawyers. His review omitted published papers that indicate that short fiber asbestos is a carcinogen. We critically review his paper.}, } @article {pmid27217757, year = {2016}, author = {Tural Onur, S and Sokucu, SN and Dalar, L and Iliaz, S and Kara, K and Buyukkale, S and Altin, S}, title = {Are neutrophil/lymphocyte ratio and platelet/lymphocyte ratio reliable parameters as prognostic indicators in malignant mesothelioma?.}, journal = {Therapeutics and clinical risk management}, volume = {12}, number = {}, pages = {651-656}, pmid = {27217757}, issn = {1176-6336}, abstract = {BACKGROUND: Malignant mesothelioma (MM) is an aggressive asbestos-related pleural tumor. The incidence is increasing with intensive use of asbestos in developing countries. We need an easily accessible, inexpensive, and reliable method for determining the low survival time prognosis of this tumor. The aim of our study was to investigate the viability of neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) as prognostic indicators in MM.

PATIENTS AND METHODS: Thirty-six patients with MM, whose histopathologic diagnosis and follow-up were performed by our clinic and whose complete archive data were accessible, were included in this retrospective study. The patients' histopathologic disease types and stages, complete blood count parameters at diagnosis, and survival were recorded.

RESULTS: Eighteen of the patients with MM were male and the remaining 18 of them were female; the average follow-up period was 24.83±3.61 months. The PLR levels of the patients were statistically significant (P<0.05). The NLR and PLR area under the receiver operating characteristic curve values were 0.559 and 0.749, respectively (P=0.631 and P=0.044, respectively).

CONCLUSION: PLR was a significant prognostic indicator of MM at diagnosis on complete blood count parameters; however, NLR was not a significant prognostic indicator. A large number of prospective studies are needed to prove the reliability of the parameters.}, } @article {pmid27210080, year = {2016}, author = {Kishimoto, T and Fujimoto, N and Nishi, H}, title = {[Clinical Pathological Diagnosis, and Treatment for Pleural Mesothelioma].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {43}, number = {5}, pages = {513-517}, pmid = {27210080}, issn = {0385-0684}, mesh = {Antineoplastic Agents/therapeutic use ; Biopsy ; Humans ; Lung Neoplasms/complications/*diagnosis/genetics/*therapy ; Mesothelioma/complications/*diagnosis/genetics/*therapy ; Mesothelioma, Malignant ; Pleural Effusion/etiology ; Pleural Neoplasms/complications/*diagnosis/genetics/*therapy ; }, abstract = {For the differential diagnosis between fibrous pleuritis and other malignancies such as lung cancer, multiple immunostaining is essential to diagnose pleural mesothelioma. For cytological diagnosis of pleural effusions, differentiation between mesothelioma cells and reactive mesothelial cells is very difficult. Therefore, histological diagnoses of tumor tissues obtained via biopsy are essential. To diagnose epthelioid mesothelioma, more than 2 positive and negative markers must be consistent with those known for mesothelioma. To diagnose sarcomatoid mesothelioma, keratin is usually positive, differentiating the diagnosis from that for real sarcoma. For surgical treatment for pleural mesothelioma, extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D) are usually performed. The proportion of P/D increases because of the low death rates with surgery and similar survivals. However, a trimodal approach, such as EPP with chemotherapy and radiotherapy, is best for longer survival and expected to be curative. For chemotherapy, only cisplatin (CDDP) combined with pemetrexed (PEM) is effective, and no other agents have been identified for this disease. Nowadays, clinical immunotherapy trials start with phase II study.}, } @article {pmid27188278, year = {2016}, author = {Boffetta, P}, title = {Response to: Pleural mesothelioma, and occupational and non-occupational asbestos exposure: a case-control study with quantitative risk assessment.}, journal = {Occupational and environmental medicine}, volume = {73}, number = {10}, pages = {712}, doi = {10.1136/oemed-2016-103776}, pmid = {27188278}, issn = {1470-7926}, mesh = {*Asbestos ; Case-Control Studies ; Humans ; Mesothelioma ; Occupational Diseases ; Occupational Exposure ; *Pleural Neoplasms ; Risk Assessment ; }, } @article {pmid27187383, year = {2016}, author = {Lai, J and Zhou, Z and Tang, XJ and Gao, ZB and Zhou, J and Chen, SQ}, title = {A Tumor-Specific Neo-Antigen Caused by a Frameshift Mutation in BAP1 Is a Potential Personalized Biomarker in Malignant Peritoneal Mesothelioma.}, journal = {International journal of molecular sciences}, volume = {17}, number = {5}, pages = {}, pmid = {27187383}, issn = {1422-0067}, mesh = {Aged ; Amino Acid Sequence ; Antigen Presentation/immunology ; Antigens, Neoplasm/*genetics ; Biomarkers, Tumor/*genetics ; Blotting, Western ; Female ; Frameshift Mutation/*genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Immunohistochemistry ; Lung Neoplasms/*genetics ; Major Histocompatibility Complex ; Mesothelioma/*genetics ; Mesothelioma, Malignant ; Models, Biological ; Molecular Weight ; Peritoneal Neoplasms/*genetics ; *Precision Medicine ; Reproducibility of Results ; Signal Transduction ; Tumor Suppressor Proteins/chemistry/*genetics ; Ubiquitin Thiolesterase/chemistry/*genetics ; }, abstract = {Malignant peritoneal mesothelioma (MPM) is an aggressive rare malignancy associated with asbestos exposure. A better understanding of the molecular pathogenesis of MPM will help develop a targeted therapy strategy. Oncogene targeted depth sequencing was performed on a tumor sample and paired peripheral blood DNA from a patient with malignant mesothelioma of the peritoneum. Four somatic base-substitutions in NOTCH2, NSD1, PDE4DIP, and ATP10B and 1 insert frameshift mutation in BAP1 were validated by the Sanger method at the transcriptional level. A 13-amino acids neo-peptide of the truncated Bap1 protein, which was produced as a result of this novel frameshift mutation, was predicted to be presented by this patient's HLA-B protein. The polyclonal antibody of the synthesized 13-mer neo-peptide was produced in rabbits. Western blotting results showed a good antibody-neoantigen specificity, and Immunohistochemistry (IHC) staining with the antibody of the neo-peptide clearly differentiated neoplastic cells from normal cells. A search of the Catalogue of Somatic Mutations in Cancer (COSMIC) database also revealed that 53.2% of mutations in BAP1 were frameshift indels with neo-peptide formation. An identified tumor-specific neo-antigen could be the potential molecular biomarker for personalized diagnosis to precisely subtype rare malignancies such as MPM.}, } @article {pmid27185582, year = {2016}, author = {Reid, G and Kao, SC and Pavlakis, N and Brahmbhatt, H and MacDiarmid, J and Clarke, S and Boyer, M and van Zandwijk, N}, title = {Clinical development of TargomiRs, a miRNA mimic-based treatment for patients with recurrent thoracic cancer.}, journal = {Epigenomics}, volume = {8}, number = {8}, pages = {1079-1085}, doi = {10.2217/epi-2016-0035}, pmid = {27185582}, issn = {1750-192X}, mesh = {*Clinical Trials, Phase I as Topic ; Humans ; Lung Neoplasms/*therapy ; Mesothelioma/*therapy ; Mesothelioma, Malignant ; RNAi Therapeutics/*methods ; Thoracic Neoplasms/*therapy ; }, abstract = {miRNAs are responsible for post-transcriptional control of gene expression, and are frequently downregulated in cancer. It has become well established that restoring miRNA levels can inhibit tumor growth, and many studies have demonstrated this in preclinical models. This in turn has led to the first clinical trials of miRNA replacement therapy. This special report focuses on the development of TargomiRs - miRNA mimics delivered by targeted bacterial minicells - and the very first clinical experience of a miRNA replacement therapy in thoracic cancer patients in the Phase I MesomiR-1 trial.}, } @article {pmid27184482, year = {2016}, author = {Chirac, P and Maillet, D and Leprêtre, F and Isaac, S and Glehen, O and Figeac, M and Villeneuve, L and Péron, J and Gibson, F and Galateau-Sallé, F and Gilly, FN and Brevet, M}, title = {Genomic copy number alterations in 33 malignant peritoneal mesothelioma analyzed by comparative genomic hybridization array.}, journal = {Human pathology}, volume = {55}, number = {}, pages = {72-82}, doi = {10.1016/j.humpath.2016.04.015}, pmid = {27184482}, issn = {1532-8392}, mesh = {Adolescent ; Adult ; Aged ; Asbestos/adverse effects ; Biomarkers, Tumor/*genetics ; Chromosomal Instability ; *Comparative Genomic Hybridization ; *DNA Copy Number Variations ; Female ; France ; *Gene Amplification ; *Gene Dosage ; Genetic Predisposition to Disease ; Humans ; Immunohistochemistry ; Inhalation Exposure/adverse effects ; Kaplan-Meier Estimate ; Lung Neoplasms/*genetics/mortality/pathology/therapy ; Male ; Mesothelioma/*genetics/mortality/pathology/therapy ; Mesothelioma, Malignant ; Middle Aged ; Peritoneal Neoplasms/*genetics/mortality/pathology/therapy ; Phenotype ; Predictive Value of Tests ; Prognosis ; Proportional Hazards Models ; Risk Factors ; Young Adult ; }, abstract = {Malignant peritoneal mesotheliomas (MPM) are rare, accounting for approximately 8% of cases of mesothelioma in France. We performed comparative genomic hybridization (CGH) on frozen MPM samples using the Agilent Human Genome CGH 180 K array. Samples were taken from a total of 33 French patients, comprising 20 men and 13 women with a mean (range) age of 58.4 (17-76) years. Asbestos exposure was reported in 8 patients (24.2%). Median (range) overall survival (OS) was 39 (0-119) months. CGH analysis demonstrated the presence of chromosomal instability in patients with MPM, with a genomic pattern that was similar to that described for pleural mesothelioma, including the loss of chromosomal regions 3p21, 9p21, and 22q12. In addition, novel genomic copy number alterations were identified, including the 15q26.2 region and the 8p11.22 region. Median OS was associated with a low peritoneal cancer index (P=.011), epithelioid subtype (P=.038), and a low number of genomic aberrations (P=.015), all of which constitute good prognostic factors for MPM. Our results provide new insights into the genetic and genomic background of MPM. Although pleural and peritoneal mesotheliomas have different risk factors, different therapeutics, and different prognosis; these data provide support to combine pleural and peritoneal mesothelioma in same clinical assays.}, } @article {pmid27181379, year = {2016}, author = {Betti, M and Aspesi, A and Biasi, A and Casalone, E and Ferrante, D and Ogliara, P and Gironi, LC and Giorgione, R and Farinelli, P and Grosso, F and Libener, R and Rosato, S and Turchetti, D and Maffè, A and Casadio, C and Ascoli, V and Dianzani, C and Colombo, E and Piccolini, E and Pavesi, M and Miccoli, S and Mirabelli, D and Bracco, C and Righi, L and Boldorini, R and Papotti, M and Matullo, G and Magnani, C and Pasini, B and Dianzani, I}, title = {CDKN2A and BAP1 germline mutations predispose to melanoma and mesothelioma.}, journal = {Cancer letters}, volume = {378}, number = {2}, pages = {120-130}, doi = {10.1016/j.canlet.2016.05.011}, pmid = {27181379}, issn = {1872-7980}, mesh = {Adolescent ; Adult ; Aged ; Biomarkers, Tumor/analysis/*genetics ; *Codon, Nonsense ; Cyclin-Dependent Kinase Inhibitor p16 ; Cyclin-Dependent Kinase Inhibitor p18/analysis/*genetics ; DNA Mutational Analysis ; Databases, Factual ; Female ; Genetic Association Studies ; Genetic Predisposition to Disease ; *Germ-Line Mutation ; Heredity ; Humans ; Immunohistochemistry ; Italy ; Male ; Melanoma/chemistry/*genetics/pathology ; Mesothelioma/chemistry/*genetics/pathology ; Middle Aged ; Pedigree ; Phenotype ; Risk Factors ; Skin Neoplasms/chemistry/*genetics/pathology ; Tumor Suppressor Proteins/analysis/*genetics ; Ubiquitin Thiolesterase/analysis/*genetics ; Young Adult ; }, abstract = {BAP1 germline mutations predispose to a cancer predisposition syndrome that includes mesothelioma, cutaneous melanoma, uveal melanoma and other cancers. This co-occurrence suggests that these tumors share a common carcinogenic pathway. To evaluate this hypothesis, we studied 40 Italian families with mesothelioma and/or melanoma. The probands were sequenced for BAP1 and for the most common melanoma predisposition genes (i.e. CDKN2A, CDK4, TERT, MITF and POT1) to investigate if these genes may also confer susceptibility to mesothelioma. In two out of six families with both mesothelioma and melanoma we identified either a germline nonsense mutation (c.1153C > T, p.Arg385*) in BAP1 or a recurrent pathogenic germline mutation (c.301G > T, p.Gly101Trp) in CDKN2A. Our study suggests that CDKN2A, in addition to BAP1, could be involved in the melanoma and mesothelioma susceptibility, leading to the rare familial cancer syndromes. It also suggests that these tumors share key steps that drive carcinogenesis and that other genes may be involved in inherited predisposition to malignant mesothelioma and melanoma.}, } @article {pmid27180335, year = {2016}, author = {Vangelova, K and Dimitrova, I}, title = {Asbestos exposure and mesothelioma incidence and mortality in Bulgaria.}, journal = {Reviews on environmental health}, volume = {31}, number = {2}, pages = {203-209}, doi = {10.1515/reveh-2016-0007}, pmid = {27180335}, issn = {2191-0308}, mesh = {Adult ; Aged ; Aged, 80 and over ; Air Pollutants, Occupational/*toxicity ; Asbestos/*toxicity ; Bulgaria/epidemiology ; Female ; Humans ; Incidence ; Male ; Mesothelioma/epidemiology/*etiology/mortality ; Middle Aged ; Occupational Exposure/*adverse effects ; Registries ; }, abstract = {Bulgaria totally banned the import, production and use of asbestos in 2005, but produced and used asbestos products during the last 3-4 decades of the 20th century. The aim of this study was to follow the incidence and mortality of mesothelioma in Bulgaria in relation to past occupational exposures. A literature search between 1960 and 2014 was conducted to obtain information on asbestos consumption, occupational exposure and asbestos-related diseases (ARDs). Data on registered mesotheliomas were provided by the National Cancer Register and data for recognized occupational ARDs were provided by the National Social Security Institute. An increase in the incidence of mesothelioma from 5 to 58 from 1993 to 2013, with 666 cases in the 21-year period, was registered. Incidence, mortality rates, deaths and male-to-female ratios and were lower in comparison to industrialized countries. The increase in mesothelioma incidence is considered as a consequence of more recent production and use of asbestos and asbestos products and the high occupational exposure between 1977 and 1989, while the lower rate of mesothelioma deaths and male-to-female ratio need to be investigated further.}, } @article {pmid27171110, year = {2016}, author = {Benvenuto, M and Mattera, R and Taffera, G and Giganti, MG and Lido, P and Masuelli, L and Modesti, A and Bei, R}, title = {The Potential Protective Effects of Polyphenols in Asbestos-Mediated Inflammation and Carcinogenesis of Mesothelium.}, journal = {Nutrients}, volume = {8}, number = {5}, pages = {}, pmid = {27171110}, issn = {2072-6643}, mesh = {Animals ; Asbestos/*toxicity ; Carcinogenesis/*drug effects ; Humans ; Inflammation/*chemically induced/*prevention & control ; Lung Neoplasms/chemically induced/*prevention & control ; Mesothelioma/chemically induced/*prevention & control ; Mesothelioma, Malignant ; Polyphenols/*pharmacology ; }, abstract = {Malignant Mesothelioma (MM) is a tumor of the serous membranes linked to exposure to asbestos. A chronic inflammatory response orchestrated by mesothelial cells contributes to the development and progression of MM. The evidence that: (a) multiple signaling pathways are aberrantly activated in MM cells; (b) asbestos mediated-chronic inflammation has a key role in MM carcinogenesis; (c) the deregulation of the immune system might favor the development of MM; and (d) a drug might have a better efficacy when injected into a serous cavity thus bypassing biotransformation and reaching an effective dose has prompted investigations to evaluate the effects of polyphenols for the therapy and prevention of MM. Dietary polyphenols are able to inhibit cancer cell growth by targeting multiple signaling pathways, reducing inflammation, and modulating immune response. The ability of polyphenols to modulate the production of pro-inflammatory molecules by targeting signaling pathways or ROS might represent a key mechanism to prevent and/or to contrast the development of MM. In this review, we will report the current knowledge on the ability of polyphenols to modulate the immune system and production of mediators of inflammation, thus revealing an important tool in preventing and/or counteracting the growth of MM.}, } @article {pmid27169472, year = {2016}, author = {Fritschi, L and Chan, J and Hutchings, SJ and Driscoll, TR and Wong, AY and Carey, RN}, title = {The future excess fraction model for calculating burden of disease.}, journal = {BMC public health}, volume = {16}, number = {}, pages = {386}, pmid = {27169472}, issn = {1471-2458}, mesh = {Adolescent ; Adult ; Aged ; Asbestos/*poisoning ; *Cost of Illness ; Female ; Humans ; Incidence ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Risk ; Young Adult ; }, abstract = {BACKGROUND: Estimates of the burden of disease caused by a particular agent are used to assist in making policy and prioritizing actions. Most estimations have employed the attributable fraction approach, which estimates the proportion of disease cases or deaths in a specific year which are attributable to past exposure to a particular agent. While this approach has proven extremely useful in quantifying health effects, it requires historical data on exposures which are not always available.

METHODS: We present an alternative method, the future excess fraction method, which is based on the lifetime risk approach, and which requires current rather than historical exposure data. This method estimates the future number of exposure-related disease cases or deaths occurring in the subgroup of the population who were exposed to the particular agent in a specific year. We explain this method and use publically-available data on current asbestos exposure and mesothelioma incidence to demonstrate the use of the method.

CONCLUSIONS: Our approach to modelling burden of disease is useful when there are no historical measures of exposure and where future disease rates can be projected on person years at risk.}, } @article {pmid27156205, year = {2016}, author = {Espinosa Muñoz, E and Ramírez Ocaña, D and Gutiérrez Cardo, AL}, title = {Malignant pleural mesothelioma in a young adult with no known exposure to asbestos.}, journal = {Archivos de bronconeumologia}, volume = {52}, number = {12}, pages = {615-616}, doi = {10.1016/j.arbres.2016.03.008}, pmid = {27156205}, issn = {1579-2129}, mesh = {Age of Onset ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Asbestos ; Diagnostic Errors ; Environmental Exposure ; Female ; Fever/etiology ; Humans ; Lung Neoplasms/complications/*diagnostic imaging/drug therapy/surgery ; Mesothelioma/complications/*diagnostic imaging/drug therapy/surgery ; Mesothelioma, Malignant ; Pelvic Inflammatory Disease ; Pleural Neoplasms/complications/*diagnostic imaging/drug therapy/surgery ; *Positron Emission Tomography Computed Tomography ; Risk Factors ; Shoulder Pain/etiology ; Young Adult ; }, } @article {pmid27141331, year = {2016}, author = {Cook, AM and McDonnell, AM and Lake, RA and Nowak, AK}, title = {Dexamethasone co-medication in cancer patients undergoing chemotherapy causes substantial immunomodulatory effects with implications for chemo-immunotherapy strategies.}, journal = {Oncoimmunology}, volume = {5}, number = {3}, pages = {e1066062}, pmid = {27141331}, issn = {2162-4011}, abstract = {The glucocorticoid (GC) steroid dexamethasone (Dex) is used as a supportive care co-medication for cancer patients undergoing standard care pemetrexed/platinum doublet chemotherapy. As trials for new cancer immunotherapy treatments increase in prevalence, it is important to track the immunological changes induced by co-medications commonly used in the clinic, but not specifically included in trial design or in pre-clinical models. Here, we document a number of Dex -induced immunological effects, including a large-scale lymphodepletive effect particularly affecting CD4[+] T cells but also CD8[+] T cells. The proportion of regulatory T cells within the CD4[+] compartment did not change after Dex was administered, however a significant increase in proliferation and activation of regulatory T cells was observed. We also noted Dex -induced proportional changes in dendritic cell (DC) subtypes. We discuss these immunological effects in the context of chemoimmunotherapy strategies, and suggest a number of considerations to be taken into account when designing future studies where Dex and other GCs may be in use.}, } @article {pmid27129173, year = {2016}, author = {Roulois, D and Deshayes, S and Guilly, MN and Nader, JS and Liddell, C and Robard, M and Hulin, P and Ouacher, A and Le Martelot, V and Fonteneau, JF and Grégoire, M and Blanquart, C and Pouliquen, DL}, title = {Characterization of preneoplastic and neoplastic rat mesothelial cell lines: the involvement of TETs, DNMTs, and 5-hydroxymethylcytosine.}, journal = {Oncotarget}, volume = {7}, number = {23}, pages = {34664-34687}, pmid = {27129173}, issn = {1949-2553}, mesh = {5-Methylcytosine/*analogs & derivatives/metabolism ; Animals ; Asbestos, Crocidolite/toxicity ; Biomarkers, Tumor ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Cell Transformation, Neoplastic/*pathology ; Cyclin-Dependent Kinase Inhibitor p16 ; Cyclin-Dependent Kinase Inhibitor p18/*metabolism ; DNA (Cytosine-5-)-Methyltransferases/*metabolism ; DNA Methyltransferase 3A ; Epithelial Cells/pathology ; Epithelium/pathology ; Humans ; Karyotype ; Lung Neoplasms/chemically induced/*pathology ; Mesothelioma/chemically induced/*pathology ; Mesothelioma, Malignant ; Mixed Function Oxygenases/*metabolism ; Precancerous Conditions/*pathology ; Proto-Oncogene Proteins/*metabolism ; Rats ; Rats, Inbred F344 ; }, abstract = {Malignant mesothelioma (MM) is one of the worst cancers in terms of clinical outcome, urging the need to establish and characterize new preclinical tools for investigation of the tumorigenic process, improvement of early diagnosis and evaluation of new therapeutic strategies. For these purposes, we characterized a collection of 27 cell lines established from F344 rats, after 136 to 415 days of induction with crocidolite asbestos administered intraperitoneally. Four mesotheliomas were distinguished from 23 preneoplastic mesothelial cell lines (PN) according to their propensity to generate tumors after orthotopic transplantation into syngeneic rats, their growth pattern, and the expression profile of three genes. PN cell lines were further discriminated into groups / subgroups according to morphology in culture and the expression profiles of 14 additional genes. This approach was completed by analysis of positive and negative immunohistochemical MM markers in the four tumors, of karyotype alterations in the most aggressive MM cell line in comparison with a PN epithelioid cell line, and of human normal mesothelial and mesothelioma cells and a tissue array. Our results showed that both the rat and human MM cell lines shared in common a dramatic decrease in the relative expression of Cdkn2a and of epigenetic regulators, in comparison with PN and normal human mesothelial cells, respectively. In particular, we identified the involvement of the relative expression of the Ten-Eleven Translocation (TET) family of dioxygenases and Dnmt3a in relation to the 5-hydroxymethylcytosine level in malignant transformation and the acquisition of metastatic potential.}, } @article {pmid27124367, year = {2016}, author = {Baur, X}, title = {Asbestos: Socio-legal and Scientific Controversies and Unsound Science in the Context of the Worldwide Asbestos Tragedy - Lessons to be Learned.}, journal = {Pneumologie (Stuttgart, Germany)}, volume = {70}, number = {6}, pages = {405-412}, doi = {10.1055/s-0042-103580}, pmid = {27124367}, issn = {1438-8790}, mesh = {*Asbestos ; Asbestosis/*epidemiology ; Bias ; Causality ; Evidence-Based Medicine/ethics/legislation & jurisprudence ; Global Health/ethics/legislation & jurisprudence/*statistics & numerical data ; Humans ; Lung Neoplasms/*epidemiology ; Prevalence ; Science/*legislation & jurisprudence ; Social Justice/ethics/*legislation & jurisprudence ; }, abstract = {Eight to fifteen per cent of lung cancer cases and nearly all mesothelioma cases are caused by asbestos. Problems in compensation issues ensue from strict legal requirements for eligibility and regulations of the statutory accident insurance institution pertaining to eligibility for occupational disease benefits. The latter include the unscientific requirement for set numbers of asbestos bodies or fibers to be found in lung tissue in order to "prove" disease causation if lung specimen are available. Although the validity of such evidence has been discredited by independent scientists, it is still used as evidence by an influential US pathology department. Frequently, epidemiological evidence regarding causal relationships and exposure histories is also often being ignored by insurance-affiliated medical experts.Similar misleading arguments are currently being used in newly industrialized countries where white asbestos - which is carcinogenic and fibrogenic like other asbestos types - is efficiently promoted as being less harmful. As a result, asbestos use is increasing in some of these countries. Behind the worldwide asbestos tragedy, a well-designed strategy orchestrated by certain transnational or multinational industrial interest groups can be perceived.Beyond the asbestos tragedy their covert plan is motivated by economic interests and discounts the ensuing damage to health and the impact of the diseases they create on public health systems.}, } @article {pmid27123108, year = {2016}, author = {Maki, Y and Nishimura, Y and Toyooka, S and Soh, J and Tsukuda, K and Shien, K and Furukawa, M and Muraoka, T and Ueno, T and Tanaka, N and Yamamoto, H and Asano, H and Maeda, M and Kumagai-Takei, N and Lee, S and Matsuzaki, H and Otsuki, T and Miyoshi, S}, title = {The proliferative effects of asbestos-exposed peripheral blood mononuclear cells on mesothelial cells.}, journal = {Oncology letters}, volume = {11}, number = {5}, pages = {3308-3316}, pmid = {27123108}, issn = {1792-1074}, abstract = {Malignant mesothelioma (MM) is thought to arise from the direct effect of asbestos on mesothelial cells. However, MM takes a long time to develop following exposure to asbestos, which suggests that the effects of asbestos are complex. The present study examined the effects of asbestos exposure on the cell growth of MeT-5A human mesothelial cells via cytokines produced by immune cells. Peripheral blood mononuclear cells (PBMCs) were stimulated with antibodies against cluster of differentiation (CD)3 and CD28 upon exposure to the asbestos chrysotile A (CA) or crocidolite (CR); the growth of MeT-5A cells in media supplemented with PBMC culture supernatants was subsequently examined. MeT-5A cells exhibited an increase in proliferation when grown in supernatant from the 7-day PBMC culture exposed to CA or CR. Analysis of cytokine production demonstrated increased levels of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-1α, IL-1β, IL-3, IL-5, IL-13 and IL-17A in supernatants. Individual administration of these cytokines, excluding G-CSF and GM-CSF, led to an increase in cell growth of MeT-5A, whereas this effect was not observed following the combined administration of these cytokines. The results indicate that cytokines secreted by immune cells upon exposure to asbestos cause an increase in the growth activity of mesothelial cells, suggesting that alterations in the production of cytokines by immune cells may contribute to tumorigenesis in individuals exposed to asbestos.}, } @article {pmid27110327, year = {2016}, author = {Bakhshayesh Karam, M and Karimi, S and Mosadegh, L and Chaibakhsh, S}, title = {Malignant Mesothelioma Versus Metastatic Carcinoma of the Pleura: A CT Challenge.}, journal = {Iranian journal of radiology : a quarterly journal published by the Iranian Radiological Society}, volume = {13}, number = {1}, pages = {e10949}, pmid = {27110327}, issn = {1735-1065}, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare malignant neoplasm of the pleura that typically affects individuals occupationally exposed to asbestos through a variety of industries. MPM presents with several CT features similar to more common pleural diseases such as metastatic pleural malignancy.

OBJECTIVES: The aim of this study is to differentiate malignant pleural mesothelioma from metastatic carcinoma of the pleura by pathological and radiological assessment in order to investigate accuracy of CT scan in this regard and to compare CT features of these two malignancies.

PATIENTS AND METHODS: Chest CT scans of 55 pleural malignancy patients including MPM and metastatic pleural malignancy were evaluated in this retrospective study. The pathologist made the definite diagnosis based on immunohistochemistry. A chest radiologist unaware of the pathology diagnosis observed all CT scans. Several parameters including pleural thickening, pleural effusion, thickening of inter lobar fissure, contralateral extension, contraction of involved hemithorax, parenchymal involvement (infiltration, nodules, fibrosis), pleural mediastinal involvement, lymphadenopathy, extrapleural invasion (hepatic, chest wall, diaphragm, intraperitoneal), and pericardial involvement were checked. Data analysis was carried out using SPSS version 16, and the ability of CT scan to differentiate malignant pleural mesothelioma and metastatic pleural diseases was investigated.

RESULTS: Totally 29 males and 26 females were assessed in this study. Based on pathology, 17 MPM and 38 metastatic pleural malignancies were diagnosed. According to CT study, about 82% of the patients with MPM and about 79% of the patients with metastatic pleural diseases were correctly diagnosed by a radiologist. The most common findings suggestive of MPM were pleural thickening (88.2%), loculated effusion (58.8%), and thickening of the interlobar fissure (47.1%). Whereas free pleural effusion (71.7%), parenchymal infiltration (65.8%) and pleural thickening (63.2%) were most prevalent parameters among metastatic cases.

CONCLUSION: CT scan is highly accurate in differentiating malignant pleural mesothelioma and metastatic pleural diseases. Pleural thickening and thickening of interlobar fissure lead us to the diagnosis of MPM and massive free pleural effusion is more commonly seen in metastatic pleural malignancy.}, } @article {pmid27098557, year = {2016}, author = {Suzui, M and Futakuchi, M and Fukamachi, K and Numano, T and Abdelgied, M and Takahashi, S and Ohnishi, M and Omori, T and Tsuruoka, S and Hirose, A and Kanno, J and Sakamoto, Y and Alexander, DB and Alexander, WT and Jiegou, X and Tsuda, H}, title = {Multiwalled carbon nanotubes intratracheally instilled into the rat lung induce development of pleural malignant mesothelioma and lung tumors.}, journal = {Cancer science}, volume = {107}, number = {7}, pages = {924-935}, pmid = {27098557}, issn = {1349-7006}, mesh = {Animals ; Carcinogenesis/*chemically induced ; Incidence ; Inflammation/chemically induced ; Lung/*metabolism ; Lung Neoplasms/*chemically induced ; Male ; Mesothelioma/*chemically induced ; Nanotubes, Carbon/*adverse effects/chemistry ; Organ Specificity ; *Particle Size ; Pleural Neoplasms/*chemically induced ; Rats ; Trachea/*metabolism ; }, abstract = {Multiwalled carbon nanotubes (MWCNT) have a fibrous structure and physical properties similar to asbestos and have been shown to induce malignant mesothelioma of the peritoneum after injection into the scrotum or peritoneal cavity in rats and mice. For human cancer risk assessment, however, data after administration of MWCNT via the airway, the exposure route that is most relevant to humans, is required. The present study was undertaken to investigate the carcinogenicity of MWCNT-N (NIKKISO) after administration to the rat lung. MWCNT-N was fractionated by passing it through a sieve with a pore size of 25 μm. The average lengths of the MWCNT were 4.2 μm before filtration and 2.6 μm in the flow-through fraction; the length of the retained MWCNT could not be determined. For the present study, 10-week-old F344/Crj male rats were divided into five groups: no treatment, vehicle control, MWCNT-N before filtration, MWCNT-N flow-through and MWCNT-N retained groups. Administration was by the trans-tracheal intrapulmonary spraying (TIPS) method. Rats were administered a total of 1 mg/rat during the initial 2 weeks of the experiment and then observed up to 109 weeks. The incidences of malignant mesothelioma and lung tumors (bronchiolo-alveolar adenomas and carcinomas) were 6/38 and 14/38, respectively, in the three groups administered MWCNT and 0/28 and 0/28, respectively, in the control groups. All malignant mesotheliomas were localized in the pericardial pleural cavity. The sieve fractions did not have a significant effect on tumor incidence. In conclusion, administration of MWCNT to the lung in the rat induces malignant mesothelioma and lung tumors.}, } @article {pmid27094688, year = {2016}, author = {Terracini, B and Mirabelli, D and Baur, X and Landrigan, P and , }, title = {Comments on the causation of malignant mesothelioma: Rebutting the false concept that recent exposures to asbestos do not contribute to causation of mesothelioma.}, journal = {American journal of industrial medicine}, volume = {59}, number = {6}, pages = {506-507}, doi = {10.1002/ajim.22590}, pmid = {27094688}, issn = {1097-0274}, mesh = {Asbestos/*adverse effects ; Humans ; Industry/legislation & jurisprudence ; Italy ; Liability, Legal ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; Occupational Exposure/*adverse effects/legislation & jurisprudence ; }, } @article {pmid27091358, year = {2016}, author = {Naka, T and Hatanaka, Y and Marukawa, K and Okada, H and Hatanaka, KC and Sakakibara-Konishi, J and Oizumi, S and Hida, Y and Kaga, K and Mitsuhashi, T and Matsuno, Y}, title = {Comparative genetic analysis of a rare synchronous collision tumor composed of malignant pleural mesothelioma and primary pulmonary adenocarcinoma.}, journal = {Diagnostic pathology}, volume = {11}, number = {}, pages = {38}, pmid = {27091358}, issn = {1746-1596}, mesh = {Adenocarcinoma/chemistry/*genetics/pathology/surgery ; Adenocarcinoma of Lung ; Aged ; Biomarkers, Tumor/analysis/*genetics ; *Comparative Genomic Hybridization ; DNA Copy Number Variations ; DNA Mutational Analysis ; Gene Dosage ; Genetic Predisposition to Disease ; High-Throughput Nucleotide Sequencing ; Humans ; Immunohistochemistry ; Lung Neoplasms/chemistry/*genetics/pathology/surgery ; Male ; Mesothelioma/chemistry/*genetics/pathology/surgery ; Mesothelioma, Malignant ; Mutation ; Neoplasms, Multiple Primary/chemistry/*genetics/pathology/surgery ; Phenotype ; Polymorphism, Single Nucleotide ; Predictive Value of Tests ; }, abstract = {BACKGROUND: Although asbestos acts as a potent carcinogen in pleural mesothelial and pulmonary epithelial cells, it still remains unclear whether asbestos causes specific and characteristic gene alterations in these different kinds of target cells, because direct comparison in an identical patient is not feasible. We experienced a rare synchronous collision tumor composed of malignant pleural mesothelioma (MPM) and primary pulmonary adenocarcinoma (PAC) in a 77-year-old man with a history of long-term smoking and asbestos exposure, and compared the DNA copy number alteration (CNA) and somatic mutation in these two independent tumors.

METHODS: Formalin-fixed paraffin-embedded (FFPE) tissues of MPM and PAC lesions from the surgically resected specimen were used. Each of these MPM and PAC lesions exhibited a typical histology and immunophenotype. CNA analysis using SNP array was performed using the Illumina Human Omni Express-12_FFPE (Illumina, San Diego, CA, USA) with DNA extracts from each lesion. Somatic mutation analysis using next-generation sequencing was performed using the TruSeq Amplicon Cancer Panel (Illumina).

RESULTS: The CNA analysis demonstrated a marked difference in the frequency of gain and loss between MPM and PAC. In PAC, copy number (CN) gain was detected more frequently and widely than CN loss, whereas in MPM there was no such obvious difference. PAC did not harbor CNAs that have been identified in asbestos-associated lung cancer, but did harbor some of the CNAs associated with smoking. MPM exhibited CN loss at 9p21.2-3, which is the most common genetic alteration in mesothelioma.

CONCLUSION: In this particular case, asbestos exposure may not have played a primary role in PAC carcinogenesis, but cigarette smoking may have contributed more to the occurrence of CN gains in PAC. This comparative genetic analysis of two different lesions with same amount of asbestos exposure and cigarette smoke exposure has provided information on differences in the cancer genome related to carcinogenesis.}, } @article {pmid27088640, year = {2016}, author = {Jiang, L and Chew, SH and Nakamura, K and Ohara, Y and Akatsuka, S and Toyokuni, S}, title = {Dual preventive benefits of iron elimination by desferal in asbestos-induced mesothelial carcinogenesis.}, journal = {Cancer science}, volume = {107}, number = {7}, pages = {908-915}, pmid = {27088640}, issn = {1349-7006}, mesh = {8-Hydroxy-2'-Deoxyguanosine ; Animals ; Asbestos/*toxicity ; Body Weight ; Carcinogenesis/*drug effects ; Cell Proliferation/drug effects ; Deferoxamine/*pharmacology ; Deoxyguanosine/analogs & derivatives/metabolism ; Iron/chemistry/metabolism ; Iron Chelating Agents/*pharmacology ; *Iron Deficiencies ; Macrophages/drug effects ; Male ; Neoplasms, Mesothelial/*chemically induced/metabolism/pathology/*prevention & control ; Rats ; Rats, Wistar ; }, abstract = {Asbestos-induced mesothelial carcinogenesis is currently a profound social issue due to its extremely long incubation period and high mortality rate. Therefore, procedures to prevent malignant mesothelioma in people already exposed to asbestos are important. In previous experiments, we established an asbestos-induced rat peritoneal mesothelioma model, which revealed that local iron overload is a major cause of pathogenesis and that the induced genetic alterations are similar to human counterparts. Furthermore, we showed that oral administration of deferasirox modified the histology from sarcomatoid to the more favorable epithelioid subtype. Here, we used i.p. administration of desferal to evaluate its effects on asbestos-induced peritoneal inflammation and iron deposition, as well as oxidative stress. Nitrilotriacetate was used to promote an iron-catalyzed Fenton reaction as a positive control. Desferal significantly decreased peritoneal fibrosis, iron deposition, and nuclear 8-hydroxy-2'-deoxyguanosine levels in mesothelial cells, whereas nitrilotriacetate significantly increased all of them. Desferal was more effective in rat peritoneal mesothelial cells to counteract asbestos-induced cytotoxicity than in murine macrophages (RAW264.7). Furthermore, rat sarcomatoid mesothelioma cells were more dependent on iron for proliferation than rat peritoneal mesothelial cells. Because inflammogenicity of a fiber is proportionally associated with subsequent mesothelial carcinogenesis, iron elimination from the mesothelial environment can confer dual merits for preventing asbestos-induced mesothelial carcinogenesis by suppressing inflammation and mesothelial proliferation simultaneously.}, } @article {pmid27088262, year = {2016}, author = {Yokohira, M and Nakano-Narusawa, Y and Yamakawa, K and Hashimoto, N and Yoshida, S and Kanie, S and Imaida, K}, title = {Chronic mesothelial reaction and toxicity of potassium octatitanate fibers in the pleural cavity in mice and F344 rats.}, journal = {Cancer science}, volume = {107}, number = {7}, pages = {1047-1054}, pmid = {27088262}, issn = {1349-7006}, mesh = {Animals ; Body Weight/drug effects ; Female ; Kidney/drug effects/pathology ; Liver/drug effects/pathology ; Lung/drug effects/pathology ; Male ; Mesothelioma/*chemically induced/pathology ; Mice ; Mice, Inbred Strains ; Nitrosamines/toxicity ; Organ Size/drug effects ; Particle Size ; Pleural Cavity/*drug effects/pathology ; Rats ; Rats, Inbred F344 ; Species Specificity ; Titanium/chemistry/*toxicity ; }, abstract = {Fiber-shaped particles of potassium octatitanate (tradename TISMO; chemical formula K2 O·6TiO2), which are morphologically similar to asbestos particles, were shown to induce severe proliferative reactions in the pleural mesothelium in a previous experiment carried out over 21 weeks. The present study aims to determine whether these fibers induce malignant mesotheliomas in rodents, and to examine chronic toxicity induced. Additionally, we investigated the specific differences observable between the biological responses to the direct infusion of the fibers alone into the pleural cavity and those induced by the co-administration of the fibers with a known carcinogen. To detect the induction of malignant pleural mesotheliomas, two experiments were undertaken. In Experiment 1, four strains of mice, A/J, C3H, ICR, and C57BL, were examined for 52 weeks after experimental treatment with TISMO. In Experiment 2, the F344 rats were treated with TISMO alone, the lung carcinogen N-bis (2-hydroxypropyl) nitrosamine (DHPN) alone, both TISMO and DHPN, or left untreated and were then examined for 52 weeks. In this experiment, malignant lesion induction was expected in the co-administration group. TISMO fibers were observed in the alveoli, indicating penetration through the visceral pleura in mice and rats. The histopathological detection of TISMO fibers in the liver and kidneys of mice and rats indicated migration of the fibers out of the pleural cavity. Atypical mesothelial cells with severe pleural proliferation were observed, but malignant mesotheliomas were not detected. Among the rats, there were no observed malignant alterations in the mesothelium induced by DHPN-TISMO co-administration.}, } @article {pmid27087035, year = {2016}, author = {Fazzo, L and Carere, M and Tisano, F and Bruno, C and Cernigliaro, A and Cicero, MR and Comba, P and Contrino, ML and De Santis, M and Falleni, F and Ingallinella, V and Madeddu, A and Marcello, I and Regalbuto, C and Sciacca, G and Soggiu, ME and Zona, A}, title = {Cancer incidence in Priolo, Sicily: a spatial approach for estimation of industrial air pollution impact.}, journal = {Geospatial health}, volume = {11}, number = {1}, pages = {320}, doi = {10.4081/gh.2016.320}, pmid = {27087035}, issn = {1970-7096}, mesh = {Air Pollution/*adverse effects/statistics & numerical data ; Carcinogens, Environmental/adverse effects ; Cluster Analysis ; Environmental Exposure/adverse effects ; Female ; Humans ; Incidence ; Male ; Neoplasms/chemically induced/*epidemiology ; Sicily/epidemiology ; Spatial Analysis ; }, abstract = {The territory around the industrial Sicilian area of Priolo, Italy, has been defined as a contaminated site (CS) of national priority for remediation because of diffuse environmental contamination caused by large industrial settlements. The present study investigates the spatial distribution of cancer into the CS territory (period 1999-2006). Different geographical methods used for the evaluation of the impact of industrial air pollutants were adopted. Using the database of Syracuse Province Cancer Registry, gender-specific standardised incidence ratios were calculated for 35 tumour sites for the CS overall and for each municipality included in the CS. A cluster analysis for 17 selected neoplasms was performed at micro-geographical level. The identification of the priority index contaminants (PICs) present in environmental matrices and a review of their carcinogenicity have been performed and applied in the interpretation of the findings. The area has a higher cancer incidence with respect to the provincial population, in particular excess is registered among both genders of lung, bladder and breast cancers as well as skin melanoma and pleural mesothelioma and there is an a priori evidence of association with the exposure to PICs. The study highlights the need to provide different approaches in CSs where several exposure pathways might be relevant for the population. The presence of potential sources of asbestos exposure deserves specific concern.}, } @article {pmid27083413, year = {2016}, author = {Gavett, SH and Parkinson, CU and Willson, GA and Wood, CE and Jarabek, AM and Roberts, KC and Kodavanti, UP and Dodd, DE}, title = {Persistent effects of Libby amphibole and amosite asbestos following subchronic inhalation in rats.}, journal = {Particle and fibre toxicology}, volume = {13}, number = {}, pages = {17}, pmid = {27083413}, issn = {1743-8977}, mesh = {Adenocarcinoma, Bronchiolo-Alveolar/*chemically induced/genetics/metabolism/pathology ; Adenoma/*chemically induced/metabolism/pathology ; Animals ; Apoptosis/drug effects ; Asbestos, Amosite/*toxicity ; Asbestos, Amphibole/*toxicity ; Cell Proliferation/drug effects ; Cell Transformation, Neoplastic/chemically induced ; Cytokines/genetics/metabolism ; Dose-Response Relationship, Drug ; Epithelial Cells/drug effects/metabolism/pathology ; Hyperplasia ; Inflammation Mediators/metabolism ; *Inhalation Exposure ; Lung/*drug effects/metabolism/pathology ; Lung Neoplasms/*chemically induced/genetics/metabolism/pathology ; Male ; Pneumonia/*chemically induced/genetics/metabolism/pathology ; Pulmonary Fibrosis/*chemically induced/genetics/metabolism/pathology ; Rats, Inbred F344 ; Risk Assessment ; Signal Transduction/drug effects ; Time Factors ; }, abstract = {BACKGROUND: Human exposure to Libby amphibole (LA) asbestos increases risk of lung cancer, mesothelioma, and non-malignant respiratory disease. This study evaluated potency and time-course effects of LA and positive control amosite (AM) asbestos fibers in male F344 rats following nose-only inhalation exposure.

METHODS: Rats were exposed to air, LA (0.5, 3.5, or 25.0 mg/m(3) targets), or AM (3.5 mg/m(3) target) for 10 days and assessed for markers of lung inflammation, injury, and cell proliferation. Short-term results guided concentration levels for a stop-exposure study in which rats were exposed to air, LA (1.0, 3.3, or 10.0 mg/m(3)), or AM (3.3 mg/m(3)) 6 h/day, 5 days/week for 13 weeks, and assessed 1 day, 1, 3, and 18 months post-exposure. Fibers were relatively short; for 10 mg/m(3) LA, mean length of all structures was 3.7 μm and 1% were longer than 20 μm.

RESULTS: Ten days exposure to 25.0 mg/m(3) LA resulted in significantly increased lung inflammation, fibrosis, bronchiolar epithelial cell proliferation and hyperplasia, and inflammatory cytokine gene expression compared to air. Exposure to 3.5 mg/m(3) LA resulted in modestly higher markers of acute lung injury and inflammation compared to AM. Following 13 weeks exposure, lung fiber burdens correlated with exposure mass concentrations, declining gradually over 18 months. LA (3.3 and 10.0 mg/m(3)) and AM produced significantly higher bronchoalveolar lavage markers of inflammation and lung tissue cytokines, Akt, and MAPK/ERK pathway components compared to air control from 1 day to 3 months post-exposure. Histopathology showed alveolar inflammation and interstitial fibrosis in all fiber-exposed groups up to 18 months post-exposure. Positive dose trends for incidence of alveolar epithelial hyperplasia and bronchiolar/alveolar adenoma or carcinoma were observed among LA groups.

CONCLUSIONS: Inhalation of relatively short LA fibers produced inflammatory, fibrogenic, and tumorigenic effects in rats which replicate essential attributes of asbestos-related disease in exposed humans. Fiber burden, inflammation, and activation of growth factor pathways may persist and contribute to lung tumorigenesis long after initial LA exposure. Fiber burden data are being used to develop a dosimetry model for LA fibers, which may provide insights on mode of action for hazard assessment.}, } @article {pmid27070945, year = {2016}, author = {Kraynie, A and de Ridder, GG and Sporn, TA and Pavlisko, EN and Roggli, VL}, title = {Malignant mesothelioma not related to asbestos exposure: Analytical scanning electron microscopic analysis of 83 cases and comparison with 442 asbestos-related cases.}, journal = {Ultrastructural pathology}, volume = {40}, number = {3}, pages = {142-146}, doi = {10.3109/01913123.2016.1154633}, pmid = {27070945}, issn = {1521-0758}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*analysis ; Female ; Humans ; Lung/ultrastructure ; Male ; Mesothelioma/*pathology ; Microscopy, Electron, Scanning ; Middle Aged ; Peritoneal Neoplasms/*pathology ; Pleural Neoplasms/*pathology ; }, abstract = {Epidemiological studies indicate that 80-90% of mesotheliomas are asbestos related. This suggests that 10-20% are not. Lung fiber burden analysis provides objective information about past exposures to asbestos. We have performed lung fiber burden analysis on a large cohort of mesothelioma cases and compared the findings with a reference population. Herein we report our findings along with demographic and exposure data.}, } @article {pmid27069474, year = {2016}, author = {Su, SS and Zheng, GQ and Liu, YG and Chen, YF and Song, ZW and Yu, SJ and Sun, NN and Yang, YX}, title = {Malignant Peritoneum Mesothelioma with Hepatic Involvement: A Single Institution Experience in 5 Patients and Review of the Literature.}, journal = {Gastroenterology research and practice}, volume = {2016}, number = {}, pages = {6242149}, pmid = {27069474}, issn = {1687-6121}, abstract = {Malignant peritoneal mesothelioma with invasion of the liver is an invariably fatal disease. We aimed to clarify the characteristics of malignant peritoneal mesothelioma cases with liver involvement. The clinical presentation, computed tomography images, and immunohistochemical and histopathological features of 5 patients with malignant peritoneal mesothelioma and liver involvement were evaluated. The diagnosis was established by imaging and immune profiles of the tumours. A review of 8 cases with primary or invading malignant mesothelioma in liver is presented. All 5 mesothelioma cases were asbestos-related. CT images of malignant peritoneal mesothelioma with the liver involvement typically showed that the lesion grew inside the liver along the capsule and was possibly accompanied by capsule breakthrough and extrahepatic infiltration. The tumours exhibited a common epithelioid appearance in all 5 patients and most cases revealed positive Cal, CK, and MC with negative CEA and HeP. Different from our findings, the review of literature revealed that most malignant mesothelioma of liver was due to primary intrahepatic malignant mesothelioma. Finally, we concluded that the diagnosis of malignant peritoneal mesothelioma cases with liver invasion is reliably achieved by the history of asbestos exposure, the characteristic CT imaging, and immune profiles of the tumours.}, } @article {pmid27068941, year = {2016}, author = {Thayaparan, T and Spicer, JF and Maher, J}, title = {The role of the HGF/Met axis in mesothelioma.}, journal = {Biochemical Society transactions}, volume = {44}, number = {2}, pages = {363-370}, doi = {10.1042/BST20150252}, pmid = {27068941}, issn = {1470-8752}, mesh = {Animals ; Hepatocyte Growth Factor/*physiology ; Humans ; Lung Neoplasms/pathology/*physiopathology ; Mesothelioma/pathology/*physiopathology ; Mesothelioma, Malignant ; Mutation ; Proto-Oncogene Proteins c-met/genetics/*physiology ; }, abstract = {Malignant mesothelioma is an asbestos-related cancer that occurs most commonly in the pleural space and is incurable. Increasing evidence suggests that aberrant receptor tyrosine kinase (RTK)-directed signalling plays a key role in the pathogenesis of this cancer. In the majority of mesotheliomas, up-regulated expression or signalling by Met, the receptor for hepatocyte growth factor (HGF) can be demonstrated. Following binding of ligand, Met relays signals that promote cell survival, proliferation, movement, invasiveness, branching morphogenesis and angiogenesis. Here we describe the HGF/Met axis and review the mechanisms that lead to the aberrant activation of this signalling system in mesothelioma. We also describe the cross-talk that occurs between HGF/Met and a number of other receptors, ligands and co-receptor systems. The prevalent occurrence of HGF/Met dysregulation in patients with mesothelioma sets the scene for the investigation of pharmaceutical inhibitors of this axis. In light of the inter-relationship between HGF/Met and other ligand receptor, combinatorial targeting strategies may provide opportunities for therapeutic advancement in this challenging tumour.}, } @article {pmid27055148, year = {2016}, author = {Maggioni, C and Barletta, G and Rijavec, E and Biello, F and Gualco, E and Grossi, F}, title = {Advances in treatment of mesothelioma.}, journal = {Expert opinion on pharmacotherapy}, volume = {17}, number = {9}, pages = {1197-1205}, doi = {10.1080/14656566.2016.1176145}, pmid = {27055148}, issn = {1744-7666}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Combined Modality Therapy/trends ; Humans ; Immunotherapy/adverse effects/trends ; Lung Neoplasms/diagnosis/*therapy ; Mesothelioma/diagnosis/*therapy ; Mesothelioma, Malignant ; Pleural Neoplasms/diagnosis/*therapy ; Prognosis ; *Therapies, Investigational/methods/trends ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is an uncommon, aggressive cancer, derived from pleural mesothelial cells, that has a close relationship to asbestos exposure. To date, MPM prognosis is poor and very few treatment options are available for both localized and advanced MPM.

AREAS COVERED: The standard of care is still chemotherapy with platinum derivates and antifolate agents. In the last few years, several new agents have been studied on the basis of mesothelioma carcinogenesis and invasiveness mechanisms; however, the recent results are poor and few drugs have been tested in phase III trials because of toxicity or because they did not improve patient outcomes. The aim of this review is to focus on the current available treatment for MPM through the analysis of the results comes from the phase III trials and to discuss the future perspectives in the pathogenesis, diagnosis and treatment.

EXPERT OPINION: Many compounds are currently under investigation in different subsets of patients. Interesting data have come from preliminary studies on immunotherapy, but randomized studies are needed to confirm the preliminary positive results of this new strategy. A better comprehension of MPM pathogenesis should be obtained to improve and develop new diagnostic tools and target therapies.}, } @article {pmid27042963, year = {2016}, author = {Matsuzaki, H and Lee, S and Maeda, M and Kumagai-Takei, N and Nishimura, Y and Otsuki, T}, title = {FoxO1 regulates apoptosis induced by asbestos in the MT-2 human T-cell line.}, journal = {Journal of immunotoxicology}, volume = {13}, number = {5}, pages = {620-627}, doi = {10.3109/1547691X.2016.1143539}, pmid = {27042963}, issn = {1547-6901}, mesh = {Apoptosis/genetics ; Apoptosis Regulatory Proteins/genetics/metabolism ; Asbestos/administration & dosage/adverse effects/*immunology ; Bcl-2-Like Protein 11/genetics/metabolism ; Cell Line ; Down-Regulation ; Fas Ligand Protein/genetics/metabolism ; Forkhead Box Protein O1/genetics/*metabolism ; Humans ; Lung Neoplasms/chemically induced/*immunology ; Mesothelioma/chemically induced/*immunology ; Proto-Oncogene Proteins/genetics/metabolism ; RNA, Messenger/analysis ; RNA, Small Interfering/genetics ; Signal Transduction ; T-Lymphocytes/*physiology ; }, abstract = {Asbestos is known to cause malignant mesothelioma and lung cancer. Recent studies implicate tumor immunity in the development of various tumors, including malignant mesothelioma. In order to establish an in vitro T-cell model to clarify the effects of long-term exposure of asbestos on tumor immunity, in this study, human T-cell line MT-2 cells were cultured with asbestos for longer than 8 months and the resultant cells (MT-2Rst) were assessed for the expression of forkhead transcription factor FoxO1. Gene expression analysis revealed that the amount of FoxO1 mRNA decreased after long-term exposure of the MT-2 cells to asbestos. In accordance with this reduction in FoxO1, pro-apoptotic Foxo1 target genes Puma, Fas ligand and Bim were also seen to be down-regulated in MT-2Rst cells. Furthermore, shRNA-mediated knock-down of FoxO1 reduced the number of apoptotic parental MT-2 cells after treatment with asbestos. On the other hand, over-expression of FoxO1 did not affect asbestos-induced apoptosis in MT-2Rst cells. These results suggested that FoxO1 played an important role in regulating asbestos-induced apoptosis and confirmed the presence of multiple pathways regulating resistance to asbestos in MT-2Rst cells.}, } @article {pmid27041164, year = {2016}, author = {Hirooka, A and Tamiya, A and Kanazu, M and Nonaka, J and Yonezawa, T and Asami, K and Atagi, S}, title = {Brain Metastasis of Pleural Mesothelioma after a Subarachnoid Hemorrhage.}, journal = {Internal medicine (Tokyo, Japan)}, volume = {55}, number = {7}, pages = {779-781}, doi = {10.2169/internalmedicine.55.3765}, pmid = {27041164}, issn = {1349-7235}, mesh = {Autopsy ; Brain/pathology ; Brain Neoplasms/*complications/*secondary/surgery ; Humans ; Lung Neoplasms/*pathology ; Male ; Mesothelioma/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Subarachnoid Hemorrhage/*complications ; }, abstract = {Malignant pleural mesothelioma (MPM) is an uncommon, fatal neoplasm induced by asbestos exposure. Brain metastases from MPM are extremely rare, with most such cases diagnosed only at the time of autopsy. This report describes what we believe to be the first case of MPM metastasizing to the brain after a subarachnoid hemorrhage, as well as the subsequent surgical removal of the brain metastasis.}, } @article {pmid27040844, year = {2016}, author = {Butnor, KJ and Brownlee, NA and Mahar, A and Pavlisko, EN and Sporn, TA and Roggli, VL}, title = {Diffuse malignant mesothelioma and synchronous lung cancer: A clinicopathological study of 18 cases.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {95}, number = {}, pages = {1-7}, doi = {10.1016/j.lungcan.2016.02.007}, pmid = {27040844}, issn = {1872-8332}, mesh = {Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Biomarkers ; Biopsy ; Databases, Factual ; Female ; Humans ; Immunohistochemistry ; Lung Neoplasms/*diagnosis/*epidemiology/etiology ; Male ; Mesothelioma/*diagnosis/*epidemiology/etiology ; Mesothelioma, Malignant ; Middle Aged ; Neoplasms, Multiple Primary/*diagnosis/*epidemiology/etiology ; Occupational Exposure/adverse effects ; }, abstract = {OBJECTIVES: To examine the clinicopathologic characteristics of individuals with diffuse malignant mesothelioma (DMM) occurring concurrently with lung cancer (LC).

MATERIALS AND METHODS: A database of approximately 3800 patients with DMM was reviewed, from which 18 patients (0.5%) who had synchronous LC were identified. The clinicopathologic features, as well as the occupational exposure history and fiber burden analysis data were examined.

RESULTS: The patient median age was 68 years (range 58-84 years). Of the 18 patients (14 male, 4 female), 11 (61%) had epithelial, 5 (28%) had biphasic, and 2 (11%) had sarcomatoid DMM, with the majority (16 cases; 89%) originating in the pleura and only 2 were peritoneal. Among the histologic types of LC, adenocarcinoma was most frequent (12 cases; 67%), while 5 cases of squamous cell carcinoma, and 1 case of small cell carcinoma were observed. Three patients also had a history of prior malignancy (1 with testicular seminoma and bladder carcinoma and 2 with prostate carcinoma). Fifteen patients had a positive smoking history. All but 3 had documented asbestos exposure. Three had histologic features of asbestosis. Mineral analysis performed in 8 showed an elevated asbestos fiber burden in 4 (22%). Amosite was detected in 4 patients, crocidolite in 3, and non-commercial amphiboles in 5.

CONCLUSION: The finding of simultaneous carcinoma of the lung and DMM is distinctly unusual. The majority of patients are male smokers with pleural epithelial DMM and lung adenocarcinoma. This study represents the largest cohort of patients reported to date with synchronous malignant mesothelioma and lung cancer, and we propose guidelines for making a diagnosis of synchronous malignant mesothelioma and primary lung cancer.}, } @article {pmid27040480, year = {2016}, author = {Ramazzini, C}, title = {Comments on the causation of malignant mesothelioma: rebutting the false concept that recent exposures to asbestos do not contribute to causation of mesothelioma.}, journal = {Journal of occupational health}, volume = {58}, number = {2}, pages = {228-229}, pmid = {27040480}, issn = {1348-9585}, mesh = {*Asbestos ; Humans ; Lung Neoplasms ; *Mesothelioma ; }, } @article {pmid27034444, year = {2016}, author = {Teschke, K}, title = {Thinking about Occupation-Response and Exposure-Response Relationships: Vehicle Mechanics, Chrysotile, and Mesothelioma.}, journal = {The Annals of occupational hygiene}, volume = {60}, number = {4}, pages = {528-530}, doi = {10.1093/annhyg/mew015}, pmid = {27034444}, issn = {1475-3162}, mesh = {Asbestos, Amphibole/*toxicity ; Asbestos, Serpentine/*toxicity ; Automobiles ; Humans ; *Industry ; Mesothelioma/*chemically induced ; Occupational Exposure/*adverse effects ; }, } @article {pmid27033611, year = {2016}, author = {Cavariani, F}, title = {Asbestos contamination in feldspar extraction sites: a failure of prevention? Commentary.}, journal = {Annali dell'Istituto superiore di sanita}, volume = {52}, number = {1}, pages = {6-8}, doi = {10.4415/ANN_16_01_03}, pmid = {27033611}, issn = {2384-8553}, mesh = {Aluminum Silicates/*chemistry ; Asbestos/*chemistry ; Asbestos, Amphibole/chemistry ; Asbestosis/*etiology ; Carcinogens/*analysis ; Humans ; Italy ; *Mining ; Occupational Diseases/epidemiology ; Occupational Exposure/statistics & numerical data ; Potassium Compounds/*chemistry ; }, abstract = {Fibrous tremolite is a mineral species belonging to the amphibole group. It is present almost everywhere in the world as a natural contaminant of other minerals, like talc and vermiculite. It can be also found as a natural contaminant of the chrysotile form of asbestos. Tremolite asbestos exposures result in respiratory health consequences similar to the other forms of asbestos exposure, including lung cancer and mesothelioma. Although abundantly distributed on the earth's surface, tremolite is only rarely present in significant deposits and it has had little commercial use. Significant presence of amphibole asbestos fibers, characterized as tremolite, was identified in mineral powders coming from the milling of feldspar rocks extracted from a Sardinian mining site (Italy). This evidence raises several problems, in particular the prevention of carcinogenic risks for the workers. Feldspar is widespread all over the world and every year it is produced in large quantities and it is used for several productive processes in many manufacturing industries (over 21 million tons of feldspar mined and marketed every year). Until now the presence of tremolite asbestos in feldspar has not been described, nor has the possibility of such a health hazard for workers involved in mining, milling and handling of rocks from feldspar ores been appreciated. Therefore the need for a wider dissemination of knowledge of these problems among professionals, in particular mineralogists and industrial hygienists, must be emphasized. In fact both disciplines are necessary to plan appropriate environmental controls and adequate protections in order to achieve safe working conditions.}, } @article {pmid27032653, year = {2016}, author = {Demir, M and Kaya, H and Taylan, M and Ekinci, A and Yılmaz, S and Teke, F and Sezgi, C and Tanrikulu, AC and Meteroglu, F and Senyigit, A}, title = {Evaluation of New Biomarkers in the Prediction of Malignant Mesothelioma in Subjects with Environmental Asbestos Exposure.}, journal = {Lung}, volume = {194}, number = {3}, pages = {409-417}, pmid = {27032653}, issn = {1432-1750}, mesh = {Aged ; Area Under Curve ; Asbestos/*blood ; Biomarkers, Tumor/*blood ; Case-Control Studies ; *Environmental Exposure ; ErbB Receptors/blood ; Extracellular Matrix Proteins/blood ; Female ; GPI-Linked Proteins/blood ; Humans ; Male ; Mesothelin ; Mesothelioma/*blood/diagnosis ; Middle Aged ; Peptides/blood ; Pleural Neoplasms/*blood/diagnosis ; Predictive Value of Tests ; Prospective Studies ; Syndecan-1/blood ; Thioredoxins/blood ; }, abstract = {INTRODUCTION: The purpose of this study was to investigate the potential value of certain biomarkers in predicting the presence of malignant pleural mesothelioma (MPM) in individuals environmentally exposed to asbestos.

METHODS: This prospective study investigated three groups; a control group composed of 41 healthy subjects, an asbestos exposure group consisting of 48 individuals, and a MPM group consisting of 42 patients. Serum levels of soluble mesothelin-related peptide (SMRP), thioredoxin-1 (TRX), epidermal growth factor receptor (EGFR), fibulin-3, syndecan-1 (SDC-1), and mesothelin were determined.

RESULTS: Benign pleural plaques were present in 27 (58.3 %) of the individuals in the asbestos exposure group. The asbestos exposure group had significantly higher mean TRX, SMRP, and mesothelin levels compared to the control group (p = 0.023, p = 0.011, and p < 0.001, respectively). Compared to the asbestos exposure group, the MPM group had significantly higher mean EGFR, TRX, SMRP, and fibulin-3 levels (p = 0.041, p = 0.023, p = 0.002, and p = 0.001, respectively), and significantly lower mean SDC-1 levels (p = 0.002). Unlike the other biomarkers, SMRP and TRX levels increased in a graded fashion among the control, asbestos exposure, and MPM groups, respectively. Area under the curve values for SMRP and TRX were 0.86 and 0.72, respectively (95 % CI 0.79-0.92 and p < 0.001 for SMRP, and 95 % CI 0.62-0.81 and p < 0.001 for TRX). The cut-off value for SMRP was 0.62 nmol/l (sensitivity: 97.6 %, specificity: 68.9 %, positive predictive value (PPV): 56.2 %, and negative predictive value (NPV): 98.3 %) and for TRX was 156.67 ng/ml (sensitivity: 92.9 %, specificity: 77.6 %, PPV: 41.4 %, and NPV: 92.1 %). The combination of the biomarkers reached a sensitivity of 100 %, but had lower specificity (as high as 27.7 %).

CONCLUSIONS: Serum biomarkers may be helpful for early diagnosis of MPM in asbestos-exposed cases. SMRP and TRX increased in a graded fashion from the controls to asbestos exposure and MPM groups. These two seem to be the most valuable biomarkers for the diagnosis of MPM, both individually and in combination.}, } @article {pmid27031024, year = {2016}, author = {Pierce, JS and Ruestow, PS and Finley, BL}, title = {An updated evaluation of reported no-observed adverse effect levels for chrysotile asbestos for lung cancer and mesothelioma.}, journal = {Critical reviews in toxicology}, volume = {46}, number = {7}, pages = {561-586}, doi = {10.3109/10408444.2016.1150960}, pmid = {27031024}, issn = {1547-6898}, mesh = {Asbestos, Serpentine/standards/*toxicity ; Lung Neoplasms/*chemically induced ; Mesothelioma/*chemically induced ; Mesothelioma, Malignant ; *No-Observed-Adverse-Effect Level ; Risk Assessment ; }, abstract = {Although consumption of chrysotile asbestos has decreased since the 1970s, the latency period of asbestos-related cancers is thought to be at least 20-30 years, and therefore the potential health risks associated with historical exposures is still actively researched. This analysis represents an update to a previous paper in which we evaluated the exposure-response relationships for lung cancer and mesothelioma in chrysotile-exposed cohorts. Here, we review several recently published studies as well as updated information from previous studies. For each of the 14 studies considered, we identified the "no-observed adverse effect level" (NOAEL) for lung cancer and/or mesothelioma. NOAEL values for lung cancer ranged from 1.1 to <20 f/cc-years to 1600-3200 f/cc-years, and for mesothelioma ranged from 100-400 f/cc-years to 800-1599 f/cc-years. The range of "best estimate" NOAELs was estimated to be 89-168 f/cc-years for lung cancer and 208-415 f/cc-years for mesothelioma. None of the six cohorts of cement or friction product manufacturing workers exhibited an increased lung cancer risk at any exposure level, while all of the five studies of textile workers reported an increased risk at one or more exposure levels. This is likely because friction and cement workers were exposed to much shorter chrysotile fibers. Of the seven cases of peritoneal mesothelioma reported in the included studies, none were observed in the analyses of cement or friction product manufacturing workers in the absence of crocidolite exposure. These findings will help characterize potential worker and consumer health risks associated with historical and current chrysotile exposures.}, } @article {pmid27025411, year = {2017}, author = {Naik, SL and Lewin, M and Young, R and Dearwent, SM and Lee, R}, title = {Mortality from asbestos-associated disease in Libby, Montana 1979-2011.}, journal = {Journal of exposure science & environmental epidemiology}, volume = {27}, number = {2}, pages = {207-213}, pmid = {27025411}, issn = {1559-064X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Asbestosis/mortality ; Cause of Death ; Death Certificates ; Female ; Gastrointestinal Diseases/chemically induced/mortality ; Humans ; Male ; Mesothelioma/chemically induced/mortality ; Middle Aged ; Mining ; Montana/epidemiology ; Occupational Diseases/*chemically induced/*mortality ; Occupational Exposure/*adverse effects ; Respiratory Tract Diseases/*chemically induced/*mortality ; Sex Distribution ; Young Adult ; }, abstract = {Research on asbestos exposure in Libby, MT, has focused on occupational exposure in vermiculite mining and processing, but less attention has been paid to asbestos-related mortality among community members without vermiculite mining occupational history. Our study reports on asbestos-related mortality in Libby over 33 years (1979-2011) while controlling for occupational exposure. We calculated sex-specific 33-year standardized mortality ratios (SMRs) for Libby residents who died from 1979 to 2011 with an asbestos-related cause of death. Decedent address at time of death was geocoded to confirm inclusion in the Libby County Division. We controlled for past W.R. Grace employment by including and then removing them from the SMR analysis. Six hundred and ninety-four decedents were identified as having at least one asbestos-related cause of death and residing in our study area boundary. Statistically significant (P<0.05) 33-year SMRs, both before and after controlling for W.R. Grace employment, were found for: male and female non-malignant respiratory diseases, female COPD, and asbestosis for both sexes combined. Eighty-five men and two women were matched to employment records. We observed elevated asbestos-related mortality rates among males and females. SMR results for asbestosis were high for both sexes, even after controlling for past W.R. Grace employment. These results suggest that the general population may be experiencing asbestos-related effects, not just former vermiculite workers. Additional research is needed to determine whether SMRs remain elevated after controlling for secondary exposure, such as living with vermiculite workers.}, } @article {pmid27015029, year = {2016}, author = {Barbieri, PG and Somigliana, A and Girelli, R and Lombardi, S and Sarnico, M and Silvestri, S}, title = {[Pleural mesothelioma in a school teacher: asbestos exposure due to DAS paste].}, journal = {La Medicina del lavoro}, volume = {107}, number = {2}, pages = {141-147}, pmid = {27015029}, issn = {0025-7818}, mesh = {Aged ; Asbestos, Amphibole/adverse effects ; Asbestos, Serpentine/*adverse effects ; Asbestosis/*complications/etiology/pathology ; Autopsy ; *Faculty ; Female ; Humans ; Italy ; Lung Neoplasms/*etiology/pathology ; Mesothelioma/*etiology/pathology ; Mesothelioma, Malignant ; Occupational Exposure/*adverse effects ; *Play and Playthings ; Pleural Neoplasms/*etiology/pathology ; }, abstract = {BACKGROUND: Malignant mesothelioma cases among primary school teachers are usually linked with asbestos exposure due to the mineral contained in the building structure. Among the approximately 12,000 cases of mesothelioma described in the fourth report of the National Mesothelioma Register, 11 cases of primary school teachers are reported, in spite of the fact that the "catalogue of asbestos use" does not describe circumstances of asbestos exposure other than or different to that due to asbestos contained in the buildings. Four cases in the Brescia Provincial Mesothelioma Register are identified as teachers, without this circumstance of exposure.

OBJECTIVES: To characterize the asbestos concentration and fibre type retained in the lungs of a teacher reported as a new mesothelioma case and preliminarily classified as of unknown asbestos exposure.

METHODS: The mesothelioma case presented here was diagnosed at age 78 and malignant mesothelioma was confirmed at autopsy; the patient was interviewed directly for occupational history. Samples of lung parenchyma from necropsies were collected, stored and analyzed by scanning electron microscope (SEM) and samples of DAS paste were analyzed by SEM to detect asbestos fibre content.

RESULTS: It was possible to confirm past exposure to DAS paste in forming and finishing dry items and toys during school recreational activity almost every day from the mid-60s to about the mid-70s. Subsequent SEM analysis showed: i) chrysotile fibres were found in an old and unused pack of DAS paste; ii) a lung burden of 1,400 asbestos bodies, 310.000 total asbestos fibres (33% chrysotile, 67% amphibole) and 210.000 talc fibre per gr/dry lung tissue was detected from necropsies performed on the subject. These results seem to be in agreement with an occupational exposure to asbestos due to past use of DAS paste. After the investigation, this case was reclassified from "unknowun" to " sure" occupational asbestos exposure. The occupational origin of the tumour was recognized by the Italian Workers' Compensation Authority (INAIL).

CONCLUSION: This case suggests i) the need to carry out any possible detailed studies of the circumstances and exposure sources whenever any mesothelioma case is classified as "asbestos exposure unknown", according to the guidelines of the National Mesothelioma Register, ii) handling of DAS paste can be considered as sure asbestos exposure and iii) it should be borne in mind that mesothelioma cases can occur even after cumulative low, occupational exposure, even only to chrysotile.}, } @article {pmid27009350, year = {2016}, author = {Creaney, J and Dick, IM and Musk, AW and Olsen, NJ and Robinson, BW}, title = {Immune response profiling of malignant pleural mesothelioma for diagnostic and prognostic biomarkers.}, journal = {Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals}, volume = {21}, number = {6}, pages = {551-561}, doi = {10.3109/1354750X.2016.1160429}, pmid = {27009350}, issn = {1366-5804}, mesh = {Aged ; Antibodies, Neoplasm/blood ; Antigens, Neoplasm/blood/immunology ; Asbestos/toxicity ; Autoantibodies/blood ; Biomarkers, Tumor/*blood/immunology ; Case-Control Studies ; Environmental Exposure ; Female ; Gene Ontology ; Humans ; Male ; Mesothelioma/blood/*diagnosis/immunology ; Middle Aged ; Molecular Sequence Annotation ; Pleural Neoplasms/blood/*diagnosis/immunology ; Prognosis ; Retrospective Studies ; rab GTP-Binding Proteins/immunology ; }, abstract = {The asbestos induced cancer malignant mesothelioma (MM) is difficult to diagnose and has a poor prognosis. MM is an immunological cancer, therefore autoantibodies may be suitable biomarkers and associated with prognosis. We used Protoarray(®) microarrays to determine immune responses to 8798 antigens in 10 MM and 10 asbestos exposed controls and developed diagnostic panels using 17 antigens from this. The AUC of these panels were independently tested in these 10 MM patients and controls and in a validation group of 36 controls and 35 MM patients using luminex assays; none of the antigens identified were validated. Immune responses to RAB38 were associated with a better prognosis.}, } @article {pmid26998120, year = {2016}, author = {Thanh, TD and Tho, NV and Lam, NS and Dung, NH and Tabata, C and Nakano, Y}, title = {Simian virus 40 may be associated with developing malignant pleural mesothelioma.}, journal = {Oncology letters}, volume = {11}, number = {3}, pages = {2051-2056}, pmid = {26998120}, issn = {1792-1074}, abstract = {Malignant pleural mesothelioma (MPM) is associated with a history of heavy, long-term exposure to asbestos. However, MPM may also be associated with simian virus 40 (SV40), a polyomavirus. The association between SV40 and MPM remains unclear. The present study was conducted in order to investigate the proportion of SV40 presence in the histological specimens of Vietnamese patients with MPM. Histological specimens were obtained from 45 patients (19 men and 26 women) with MPM at the Pham Ngoc Thach Hospital in Ho Chi Minh City, Vietnam. The specimens were processed and examined in order to detect the presence of the SV40 large T antigen (SV40 Tag) expression using immunohistochemistry. Of the 45 patients, 23 (51%) were epithelioid, 7 (16%) were biphasic, 6 (13%) were sarcomatoid, 4 (9%) were desmoplastic, 4 (9%) were well-differentiated papillary and 1 (2%) was the anaplastic subtype. In total, 9/45 patients (20%) demonstrated SV40 Tag expression. The proportion of patients that demonstrated SV40 Tag expression was not significantly different between the epithelioid subtype and the other subtypes (22 vs. 18%; P=1.000) or between the patients with stage IV disease and other stages (20 vs. 20%; P=1.000). The median survival time was not significantly different between the patients with or without SV40 Tag expression (196 vs. 236 days, P=0.8949). In summary, a 5th of the Vietnamese patients with MPM were associated with infection with SV40. SV40 may be a potential cause of MPM in Vietnam and this potential association requires additional studies.}, } @article {pmid26998119, year = {2016}, author = {Hong, S and Bi, MM and Zhao, PW and Wang, XU and Kong, QY and Wang, YT and Wang, L}, title = {Malignant peritoneal mesothelioma in a patient with intestinal fistula, incisional hernia and abdominal infection: A case report.}, journal = {Oncology letters}, volume = {11}, number = {3}, pages = {2047-2050}, pmid = {26998119}, issn = {1792-1074}, abstract = {Malignant mesothelioma is a rare type of cancer, most commonly associated with exposure to asbestos. Mesothelioma of the peritoneum, the membrane lining the abdominal cavity, is extremely rare. The current study reports the case of a 60-year-old female who presented with intestinal fistula, recurrent incisional hernia and abdominal infection, with no history of asbestos exposure, and was diagnosed with clear cell MPM. Computed tomography scans of the abdomen revealed extensive small bowel adhesions and massive peritoneal effusion. Histological examination of biopsy specimens indicated a diagnosis of malignant peritoneal mesothelioma with clear cell morphology. A laparotomy was performed, with subsequent resection of the bowel with fistula. Follow-up examination performed at 1-year post-surgery revealed that the patient was alive and in generally good health.}, } @article {pmid26988890, year = {2016}, author = {Oddone, E and Imbriani, M}, title = {Pleural mesothelioma: Case-report of uncommon occupational asbestos exposure in a small furniture industry.}, journal = {International journal of occupational medicine and environmental health}, volume = {29}, number = {3}, pages = {523-526}, doi = {10.13075/ijomeh.1896.00597}, pmid = {26988890}, issn = {1896-494X}, mesh = {Aged ; Asbestos/*toxicity ; Humans ; Interior Design and Furnishings ; Male ; *Manufacturing Industry ; Mesothelioma/*etiology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*etiology ; }, abstract = {The relationship between asbestos exposure and malignant mesothelioma is no longer disputed, although it is not always easy to trace past occupational exposure. This report describes a case of uncommon asbestos exposure of a small furniture industry worker, who subsequently died of pleural malignant mesothelioma, to stress the crucial importance of a full reconstruction of the occupational history, both for legal and compensation purposes. Sarcomatoid pleural mesothelioma was diagnosed in a 70-year-old man, who was previously employed as a carpenter in a small furniture industry. He worked for about 6 years in the small factory, was exposed to asbestos during the assembly of the furniture inspired by classical architecture, in which asbestos cement tubes were used to reproduce classical columns. During this production process no specific work safety measures were applied, nor masks or local aspirators. No extra-professional exposure to asbestos was identified. This mesothelioma case was investigated by the Public Prosecutor's assignment that commissioned expert evidence on the legal accountability for the disease. Despite its uncommon expositive circumstance, the length of latency (about 30 years), the duration of exposure, the clinical and histochemical features are all consistent with literature evidence, accounting for the occupational origin of this malignancy.}, } @article {pmid26988879, year = {2016}, author = {Smolková, P and Nakládalová, M and Zapletalová, J and Jakubec, P and Vildová, H and Kolek, V and Petřek, M and Nakládal, Z}, title = {Validity of mesothelin in occupational medicine practice.}, journal = {International journal of occupational medicine and environmental health}, volume = {29}, number = {3}, pages = {395-404}, doi = {10.13075/ijomeh.1896.00637}, pmid = {26988879}, issn = {1896-494X}, mesh = {Aged ; Asbestos/*toxicity ; Biomarkers, Tumor/*blood ; Female ; GPI-Linked Proteins/*blood ; Humans ; Longitudinal Studies ; Male ; Mesothelin ; Mesothelioma/blood/*diagnosis/etiology ; Middle Aged ; Occupational Exposure/*adverse effects ; Occupational Medicine/*methods ; Predictive Value of Tests ; Prospective Studies ; }, abstract = {OBJECTIVES: Malignant mesothelioma (MM) is the most serious asbestos-related disease. Its increasing incidence is alarming, suggesting the need for as early diagnosis as possible. This 4.5-year prospective longitudinal study aimed at assessing the benefit of measuring serum mesothelin as a marker for diagnosing malignant mesothelioma in individuals with previous occupational exposure to asbestos, as a part of their clinical follow-up care.

MATERIAL AND METHODS: The study comprised 309 participants (235 males, 74 females) with a mean age of 58.9 years (standard deviation (SD) = 9.8) and a mean duration of exposure to asbestos dust of 13.4 years (SD = 9.3). From 2009 to June 2013, all subjects were followed at a department of occupational medicine in Olomouc. Apart from the standard parts of medical examination (history, physical examination, simple chest radiographs and spirometry), the patients' serum mesothelin levels were determined by the Mesomark immunoenzymatic diagnostic assay. Statistical analysis of the validity of serum mesothelin level measurement was carried out with respect to the diagnosis of MM.

RESULTS: Among the participants, 16 (5.2%) individuals (14 males and 2 females) were diagnosed with malignant mesothelioma. Based on the detected mesothelin levels, their validity for prediction of malignant mesothelioma was calculated as follows: sensitivity - 0.75, specificity - 0.962, positive predictive value - 0.706, negative predictive value - 0.969, positive and negative likelihood ratios - 19.95 and 0.26, respectively, and diagnostic odds ratio - 76.8, at a 95% confidence interval.

CONCLUSIONS: The high specificity was identified indicating the low false positivity as well. In the case of detecting elevated soluble mesothelin-related peptides (SMRP) levels in formerly asbestos-exposed individuals, the possibility of the presence of MM should be included into the clinical consideration. The high negative predictive value denotes a lower probability of the presence of MM in patients with normal SMRP levels but due to the limiting lower sensitivity this possibility cannot be entirely excluded.}, } @article {pmid26976999, year = {2016}, author = {Kato, K and Gemba, K and Fujimoto, N and Aoe, K and Takeshima, Y and Inai, K and Kishimoto, T}, title = {Computed Tomographic Features of Malignant Peritoneal Mesothelioma.}, journal = {Anticancer research}, volume = {36}, number = {3}, pages = {1067-1072}, pmid = {26976999}, issn = {1791-7530}, mesh = {Diagnosis, Differential ; Female ; Humans ; Lung Neoplasms/*diagnostic imaging/*pathology ; Male ; Mesothelioma/*diagnostic imaging/*pathology ; Mesothelioma, Malignant ; Peritoneal Neoplasms/*diagnostic imaging/*pathology ; Pleural Neoplasms/pathology ; Retrospective Studies ; Tomography, X-Ray Computed ; }, abstract = {AIM: The objective of this study was to determine the computed tomographic (CT) features of malignant peritoneal mesothelioma (MPM).

PATIENTS AND METHODS: We analyzed CT features of MPM cases and compared them to those of other malignant conditions (non-MPM).

RESULTS: Multiple nodular lesions occurred more frequently in the MPM group compared to non-MPM cases (p=0.013). Thickening of the mesentery was detected more frequently in MPM cases than in non-MPM cases (56% vs. 18%, p=0.029). Pleural plaques were detected in 13 cases (45%) in the MPM group but were not detected in the non-MPM group. The MPM-CT index score, determined in each case as the sum of the findings which are potentially characteristic of MPM, was significantly higher in MPM than in non-MPM cases (p=0.001).

CONCLUSION: MPM presented characteristic CT findings, and the MPM-CT index may be useful for differential diagnosis of MPM.}, } @article {pmid26976977, year = {2016}, author = {Sasai, M and Nakamura, H and Sougawa, N and Sakurai, Y and Suzuki, M and Lee, CM}, title = {Novel Hyaluronan Formulation Enhances the Efficacy of Boron Neutron Capture Therapy for Murine Mesothelioma.}, journal = {Anticancer research}, volume = {36}, number = {3}, pages = {907-911}, pmid = {26976977}, issn = {1791-7530}, mesh = {Animals ; Boron Neutron Capture Therapy/*methods ; Cell Line, Tumor ; Cell Survival/drug effects ; Dose-Response Relationship, Drug ; Hyaluronic Acid/*administration & dosage/pharmacology ; Mesothelioma/mortality/*therapy ; Mice ; Radiation-Sensitizing Agents/*administration & dosage/pharmacology ; Survival Analysis ; Treatment Outcome ; Xenograft Model Antitumor Assays ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a refractory cancer of the pleura caused by asbestos exposure. MPM is difficult to treat because it easily disseminates. Boron neutron capture therapy (BNCT) is a radiotherapy in which cancer cells that selectively take up (10)Boron-containing compounds are destroyed, and normal cells are uninjured. Hyaluronan (HA) is a ligand of cluster of differentiation 44 (CD44), that is expressed on MPM cells.

MATERIALS AND METHODS: In order to enhance BNCT for MPM tumors, we developed a novel HA-containing (10)B (sodium borocaptate: BSH) formulation (HA-BND-S). We examined the efficacy of HA-BND-S using MPM cells and a mouse MPM model.

RESULTS: HA-BND-S preferentially bound MPM cells dose-dependently, and increased the cytotoxicity of BNCT compared to BSH in vitro. HA-BND-S administration significantly increased the survival of MPM tumor-bearing mice compared to BSH at the same (10)B dosage in BNCT.

CONCLUSION: Modifying BSH with HA is a promising strategy for enhancing the efficacy of BNCT for therapy of MPM.}, } @article {pmid26973208, year = {2016}, author = {Comar, M and Zanotta, N and Zanconati, F and Cortale, M and Bonotti, A and Cristaudo, A and Bovenzi, M}, title = {Chemokines involved in the early inflammatory response and in pro-tumoral activity in asbestos-exposed workers from an Italian coastal area with territorial clusters of pleural malignant mesothelioma.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {94}, number = {}, pages = {61-67}, doi = {10.1016/j.lungcan.2016.01.020}, pmid = {26973208}, issn = {1872-8332}, mesh = {Asbestos/*adverse effects ; Biomarkers ; Chemokines/*metabolism ; Cross-Sectional Studies ; Cytokines/metabolism ; Female ; Humans ; Inflammation/*complications/*metabolism ; Inflammation Mediators/metabolism ; Italy/epidemiology ; Lung Neoplasms/epidemiology/*etiology/*metabolism ; Male ; Mesothelioma/epidemiology/*etiology/*metabolism ; Mesothelioma, Malignant ; Occupational Exposure/adverse effects ; Pleural Neoplasms/epidemiology/*etiology/*metabolism ; }, abstract = {OBJECTIVES: Immune mediators are likely to be relevant for the biological response to asbestos exposure. The aim of this study was to investigate the association between immune mediators involved in inflammation, cell survival and angiogenesis, and asbestos-related diseases in workers from a coastal area of North-East Italy with a high incidence of pleural malignant mesothelioma (PMM).

MATERIALS AND METHODS: A selected custom set of 12 soluble mediators was evaluated with a Luminex platform in sera, pleural fluid and mesothelioma biopsies from 123 asbestos-exposed workers (38 free from pleural-pulmonary disorders, 46 with non-malignant asbestos diseases, 39 with PMM) and in sera from 33 healthy controls from the same territorial area.

RESULTS: Increased immune mediator concentrations were observed in the sera of the asbestos-exposed workers compared to controls for human fibroblast growth factor (FGF-b), vascular endothelial growth factor (VEGF), CCL5 (RANTES), CXCL10 (IP-10), CLEC11A (SCGF-b), CCL27 (CTACK), CCL11 (EOTAXIN), IL-5 and IL-6 (p<0.001). The chemokines IP-10 and RANTES were associated with the severity of asbestos-related diseases. In the workers with PMM, the immune proteins secreted by mesothelioma biopsies showed detectable levels of RANTES, VEGF, and IP-10. In the same workers with PMM, a significant relationship between serum and pleural fluid concentrations was found for RANTES alone.

CONCLUSIONS: Occupational exposure to asbestos seems to drive the production of specific growth factors dually involved in the early inflammatory response and in pro-tumoral activity before clinical evidence of related disorders, suggesting that their over-expression may precede the onset of asbestos-related diseases. These findings suggest that some chemokines may have a prognostic role in the progression of asbestos-related diseases and could be used for the health surveillance of either workers with an occupational history of asbestos exposure or patients affected by non-malignant asbestos-related diseases.}, } @article {pmid26969295, year = {2016}, author = {Peters, S and van Oyen, SC and Alfonso, H and Fritschi, L and de Klerk, NH and Reid, A and Franklin, P and Gordon, L and Benke, G and Musk, AW}, title = {Response to Kottek and Kilpatrick, 'Estimating Occupational Exposure to Asbestos in Australia'.}, journal = {The Annals of occupational hygiene}, volume = {60}, number = {4}, pages = {533-535}, doi = {10.1093/annhyg/mew010}, pmid = {26969295}, issn = {1475-3162}, mesh = {*Asbestos ; Australia ; Humans ; Mesothelioma ; Occupational Diseases ; *Occupational Exposure ; }, } @article {pmid26952387, year = {2016}, author = {Zhang, Y and Afify, A and Gandour-Edwards, RF and Bishop, JW and Huang, EC}, title = {Small cell mesothelioma: A rare entity and diagnostic pitfall mimicking small cell lung carcinoma on fine-needle aspiration.}, journal = {Diagnostic cytopathology}, volume = {44}, number = {6}, pages = {526-529}, doi = {10.1002/dc.23460}, pmid = {26952387}, issn = {1097-0339}, mesh = {Aged ; Biopsy, Fine-Needle ; Diagnosis, Differential ; Humans ; Lung Neoplasms/*pathology ; Male ; Mesothelioma/*pathology ; Small Cell Lung Carcinoma/*pathology ; }, abstract = {Small cell mesothelioma (SCM) is an extremely rare variant of epithelioid mesothelioma that can be mistaken for other forms of small round blue cell tumors, particularly small cell lung carcinoma (SCLC). Here, we describe a fine-needle aspiration (FNA) from a pleural lesion in a 75-year-old man with a history of known asbestos exposure. The FNA revealed cohesive clusters of uniform small round blue cells with high nuclear-to-cytoplasmic ratio, finely powdery chromatin, small inconspicuous nucleoli, and scant amount of cytoplasm. Mitoses were infrequent and nuclear molding was absent. Immunochemical profile supported a mesothelial origin, which was later confirmed by pleurectomy with a diagnosis of SCM. This report demonstrates the difficulties in cytologic evaluation of lung FNAs in differentiating SCM from SCLC or other small round blue cell tumors. As therapy differs for SCM, early recognition of the cytologic features is essential in making the correct diagnosis needed for appropriate clinical management. Diagn. Cytopathol. 2016;44:526-529. © 2016 Wiley Periodicals, Inc.}, } @article {pmid26951736, year = {2016}, author = {Marchiori, L and Marangi, G and Ballarin, N and Valentini, F and D'Anna, M and Barbina, P and Franchi, A and Mastrangelo, G}, title = {[Proposal of an Italian national protocol of health surveillance for former asbestos workers: an ongoing project].}, journal = {Epidemiologia e prevenzione}, volume = {40}, number = {1 Suppl 1}, pages = {68-73}, doi = {10.19191/EP16.1S1.P068.033}, pmid = {26951736}, issn = {1120-9763}, mesh = {Asbestos ; Humans ; Italy/epidemiology ; Lung Neoplasms/diagnosis ; Mesothelioma/epidemiology ; *Occupational Exposure ; Occupational Medicine ; Retrospective Studies ; }, abstract = {OBJECTIVES: to define an Italian national protocol of post-occupational health surveillance for asbestos workers according to effectiveness, appropriateness, saving, and social utility.

DESIGN: data for 1,071 former asbestos workers from several Italian Regions were collected and analysed. For these workers, a retrospective estimate of asbestos exposure was carried out. A cohort study of 1,588 asbestos workers recruited from 2000 onward during statutory health examinations in Veneto and followed-up for lung cancer mortality until December 2010 was executed. A literature search on methods of follow-up of asbestos workers (imaging, spirometry, and questionnaires) and diagnosis of non-malignant (asbestosis and pleural plaques) and malignant (lung cancer) asbestos disease was done. A consensus, i.e., a process of agreeing on one result among the participants, was made.

SETTING AND PARTICIPANTS: 19 Italian Regions (North: Veneto, Emilia-Romagna, Lombardia, Piemonte, Valle d'Aosta, Autonomous Province of Trento, Autonomous Province of Bolzano, Friuli Venezia Giulia, Liguria; Centre:Toscana, Umbria; South and Islands: Calabria, Abruzzo, Puglia, Campania, Basilicata,Marche, Sicilia, Sardegna), Department of Occupational Medicine at Italian National Institute for Compensation ofWork-Related Diseases and Accidents (INAIL), and Department of Cardiac, Thoracic, and Vascular Sciences at University of Padova.

MAIN OUTCOME MEASURES: analysis of current regional experiences on health surveillance; retrospective estimate of asbestos exposure; data collection and analysis of a cohort of asbestos workers; search of the relevant literature; final report with the consensus document.

RESULTS: the results obtained in each of the above areas of research, along with the relevant findings of the literature, were presented and discussed among the participants. The several phases of expression and evaluation of the participants' opinions were conducted according to an iterative method of investigation (Delphi method), which allows a progressive converging of different views into one shared result.

CONCLUSION: based on all the above, a consensus has been reached on a proposal for an Italian national protocol of health surveillance for asbestos workers.}, } @article {pmid26951735, year = {2016}, author = {Magnani, C and Ancona, L and Baldassarre, A and Bressan, V and Cena, T and Chellini, E and Cuccaro, F and Ferrante, D and Legittimo, P and Luberto, F and Marinaccio, A and Mattioli, S and Menegozzo, S and Merler, E and Miligi, L and Mirabelli, D and Musti, M and Oddone, E and Pavone, V and Perticaroli, P and Pettinari, A and Pirastu, R and Ranucci, A and Romeo, E and Sala, O and Scarnato, C and Silvestri, S and , }, title = {[Time trend in mesothelioma and lung cancer risk in asbestos workers in Italy].}, journal = {Epidemiologia e prevenzione}, volume = {40}, number = {1 Suppl 1}, pages = {64-67}, doi = {10.19191/EP16.1S1.P064.032}, pmid = {26951735}, issn = {1120-9763}, mesh = {Asbestos ; Asbestosis ; Female ; Humans ; Italy/epidemiology ; *Lung Neoplasms/epidemiology ; Male ; *Mesothelioma/epidemiology ; Occupational Diseases ; *Occupational Exposure ; }, abstract = {This study aims at investigating, in asbestos exposed workers, the time trend of their risk of mesothelioma and of other neoplasm after very long latency and after the cessation of asbestos exposure. We pooled a large number of Italian cohorts of asbestos workers and updated mortality follow-up. The pool of data for statistical analyses includes 51,988 workers, of which 6,058 women: 54.2% was alive at follow-up, 42.6% was dead, and 2.8%was lost. Cause of death is known for 94.3%: 2,548 deaths from lung cancer, 748 frompleural cancer, 173 fromperitoneal cancer, and 434 from asbestosis. An exposure index is being developed to compare the different cohorts. Data analysis is in progress. This study will have the size for analysing not only time trends in mesothelioma, but also the occurrence of rarer diseases and cancer specific mortality in women.}, } @article {pmid26951730, year = {2016}, author = {Merler, E and Girardi, P and Panato, C and Bressan, V}, title = {[Increased risk of mesothelioma and lung cancer among workers exposed to asbestos who could require an anticipated retirement].}, journal = {Epidemiologia e prevenzione}, volume = {40}, number = {1 Suppl 1}, pages = {26-34}, doi = {10.19191/EP16.1S1.P026.027}, pmid = {26951730}, issn = {1120-9763}, mesh = {Asbestos/adverse effects ; Humans ; Italy ; Lung Neoplasms/chemically induced ; Mesothelioma/*chemically induced ; Occupational Exposure/adverse effects ; Pleural Neoplasms/*chemically induced ; Retirement ; }, abstract = {OBJECTIVES: to assess the association among malignant pleural mesothelioma (MPM) and lung cancer (LC) among workers who have been exposed to asbestos and have or not have required an anticipated leave from work, a possibility offered by the 1992 law banning asbestos in Italy, in the framework of the health surveillance programmes on going in the Veneto Region (Northern Italy).

SETTING AND PARTICIPANTS: a cohort of asbestos workers derived from the rosters of selected factories and alive in 1992, followed from 1992 to 2012.MPM cases have been identified through the Regional Mesothelioma Registry, while LC cases through a link with the Regional Cancer Registry, hospital discharges, and death certificates. Risks related to asbestos exposure were calculated by mixed effects Poisson regression model.

RESULTS: the risk of MPM and LC increases at any additional duration of work, up to very high values for long term durations of work for MPM, and up to a three fold increase for LC. Early retirements have been requested by a fraction only in the position of submitting it.

CONCLUSION: subjects who have been exposed to asbestos should be the target of a post-occupational surveillance, and further work is suggested to identify subjects at high risk of LC because of smoking habits and more heavy exposure to asbestos, in order to develop programmes for primary and secondary cancer prevention.}, } @article {pmid26951729, year = {2016}, author = {Barone-Adesi, F and Mirabelli, D and Magnani, C}, title = {[Risk of lung cancer in individuals with previous exposure to asbestos].}, journal = {Epidemiologia e prevenzione}, volume = {40}, number = {1 Suppl 1}, pages = {20-25}, doi = {10.19191/EP16.1S1.P020.026}, pmid = {26951729}, issn = {1120-9763}, mesh = {Asbestos ; Humans ; Italy ; *Lung Neoplasms/epidemiology ; Mesothelioma/epidemiology ; *Occupational Exposure ; Smoking ; }, abstract = {Asbestos-related lung cancer is an important and partly unrecognized public health problem. The present review summarizes the knowledge regarding some specific aspects of the association between asbestos and lung cancer. It is difficult to estimate the exact number of lung cancers in a population that are attributable to asbestos exposure. However, this number is likely to greatly exceed the number of mesotheliomas. Epidemiological studies suggest that there is a linear relationship between cumulative exposure to asbestos and risk of lung cancer. Observed differences between different types of asbestos are lower than previously believed. This highlights the necessity of banning all types of asbestos worldwide. Risk of lung cancer changes with passing time from asbestos exposure, with the strongest effect observed 10-15 years after the exposure. This highlights the importance of quitting asbestos exposure as soon as possible, even for individuals with a long-term past exposure. Quitting smoking is the most important preventive action to be taken by individuals with a past exposure to asbestos. Results of recent studies show that smoking cessation is associated with a substantial reduction of lung cancer risk among individuals exposed to asbestos. This highlights the importance of promoting smoking cessation programmes specifically targeted to individuals with a past exposure to asbestos.}, } @article {pmid26951727, year = {2016}, author = {Alessi, M}, title = {[The National Asbestos Plan in Italy].}, journal = {Epidemiologia e prevenzione}, volume = {40}, number = {1 Suppl 1}, pages = {12-14}, doi = {10.19191/EP16.1S1.P012.024}, pmid = {26951727}, issn = {1120-9763}, mesh = {*Asbestos ; Humans ; Italy ; Mesothelioma ; Occupational Exposure ; Pleural Neoplasms ; }, } @article {pmid26951690, year = {2016}, author = {Marinaccio, A}, title = {[Twenty years of data in the 5th Report of the Italian National Mesothelioma Register].}, journal = {Epidemiologia e prevenzione}, volume = {40}, number = {1}, pages = {3}, doi = {10.19191/EP16.1.P003.002}, pmid = {26951690}, issn = {1120-9763}, mesh = {Asbestos/*adverse effects ; Environmental Exposure/*adverse effects ; Female ; Humans ; Incidence ; Italy/epidemiology ; Male ; Mesothelioma/diagnosis/*epidemiology/*etiology/prevention & control ; Pleural Neoplasms/diagnosis/*epidemiology/etiology/*prevention & control ; Registries/*statistics & numerical data ; Retrospective Studies ; Risk Factors ; Sex Distribution ; }, } @article {pmid26940471, year = {2016}, author = {Andersson, M and Selin, F and Järvholm, B}, title = {Asbestos exposure and the risk of sinonasal cancer.}, journal = {Occupational medicine (Oxford, England)}, volume = {66}, number = {4}, pages = {326-331}, doi = {10.1093/occmed/kqw018}, pmid = {26940471}, issn = {1471-8405}, mesh = {Adult ; Asbestos/*adverse effects ; Cohort Studies ; Humans ; Male ; Middle Aged ; Neoplasms/epidemiology/etiology ; Occupational Diseases/complications/epidemiology ; Occupational Exposure/*adverse effects ; Paranasal Sinus Diseases/epidemiology/*etiology ; Retrospective Studies ; Sweden/epidemiology ; }, abstract = {BACKGROUND: While the increased risk of lung cancer and mesothelioma is well established, the relationship between exposure to asbestos dust and sinonasal cancer is less clear.

AIMS: To study the risk of sinonasal cancer in relation to asbestos dust exposure.

METHODS: A retrospective cohort study of construction workers, linked to the Swedish Cancer Registry. Participants were classified into four exposure groups; heavy, medium, low or very low exposure to asbestos, according to the incidence of pleural mesothelioma in their occupational group. Standardized incidence ratios (SIRs) and relative risks (RRs) were analysed, adjusted for age and smoking habits. The risks of adenocarcinoma and squamous cell carcinoma were investigated separately.

RESULTS: Among the 280222 subjects, there was no increased risk of sinonasal cancer compared to the general population [SIR 0.85, 95% confidence interval (CI) 0.68-1.03], or any dose-response relationship with exposure to asbestos. The highest RR was found in the low exposure group (RR 1.25, 95% CI 0.69-2.28) and the lowest RR was found in the group with the highest exposure to asbestos (RR 0.71, 95% CI 0.33-1.53). No significantly increased risk or dose-response association could be found for adenocarcinoma or squamous cell carcinoma when analysed separately.

CONCLUSIONS: This study did not find an increased risk of developing sinonasal cancer after asbestos exposure.}, } @article {pmid26938529, year = {2016}, author = {Pietrofesa, RA and Velalopoulou, A and Albelda, SM and Christofidou-Solomidou, M}, title = {Asbestos Induces Oxidative Stress and Activation of Nrf2 Signaling in Murine Macrophages: Chemopreventive Role of the Synthetic Lignan Secoisolariciresinol Diglucoside (LGM2605).}, journal = {International journal of molecular sciences}, volume = {17}, number = {3}, pages = {322}, pmid = {26938529}, issn = {1422-0067}, support = {1R21AT008291-02/AT/NCCIH NIH HHS/United States ; 1P42ES023720-01/ES/NIEHS NIH HHS/United States ; 1P30 ES013508-02/ES/NIEHS NIH HHS/United States ; P30 ES013508/ES/NIEHS NIH HHS/United States ; P42 ES023720/ES/NIEHS NIH HHS/United States ; R21 AT008291/AT/NCCIH NIH HHS/United States ; R03 CA180548/CA/NCI NIH HHS/United States ; R01 CA133470/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antioxidants/*pharmacology ; Asbestos/*adverse effects ; Butylene Glycols/*pharmacology ; Cells, Cultured ; Glucosides/*pharmacology ; Macrophages, Peritoneal/*drug effects/metabolism ; Mice ; NF-E2-Related Factor 2/genetics/*metabolism ; *Oxidative Stress ; Signal Transduction ; }, abstract = {The interaction of asbestos fibers with macrophages generates harmful reactive oxygen species (ROS) and subsequent oxidative cell damage that are key processes linked to malignancy. Secoisolariciresinol diglucoside (SDG) is a non-toxic, flaxseed-derived pluripotent compound that has antioxidant properties and may thus function as a chemopreventive agent for asbestos-induced mesothelioma. We thus evaluated synthetic SDG (LGM2605) in asbestos-exposed, elicited murine peritoneal macrophages as an in vitro model of tissue phagocytic response to the presence of asbestos in the pleural space. Murine peritoneal macrophages (MFs) were exposed to crocidolite asbestos fibers (20 µg/cm[2]) and evaluated at various times post exposure for cytotoxicity, ROS generation, malondialdehyde (MDA), and levels of 8-iso Prostaglandin F2α (8-isoP). We then evaluated the ability of LGM2605 to mitigate asbestos-induced oxidative stress by administering LGM2605 (50 µM) 4-h prior to asbestos exposure. We observed a significant (p < 0.0001), time-dependent increase in asbestos-induced cytotoxicity, ROS generation, and the release of MDA and 8-iso Prostaglandin F2α, markers of lipid peroxidation, which increased linearly over time. LGM2605 treatment significantly (p < 0.0001) reduced asbestos-induced cytotoxicity and ROS generation, while decreasing levels of MDA and 8-isoP by 71%-88% and 41%-73%, respectively. Importantly, exposure to asbestos fibers induced cell protective defenses, such as cellular Nrf2 activation and the expression of phase II antioxidant enzymes, HO-1 and Nqo1 that were further enhanced by LGM2605 treatment. LGM2605 boosted antioxidant defenses, as well as reduced asbestos-induced ROS generation and markers of oxidative stress in murine peritoneal macrophages, supporting its possible use as a chemoprevention agent in the development of asbestos-induced malignant mesothelioma.}, } @article {pmid26937070, year = {2015}, author = {Zhang, H and Lohcharoenkal, W and Sun, J and Li, X and Wang, L and Wu, N and Rojanasakul, Y and Liu, Y}, title = {Microfluidic gradient device for studying mesothelial cell migration and the effect of chronic carbon nanotube exposure.}, journal = {Journal of micromechanics and microengineering : structures, devices, and systems}, volume = {25}, number = {7}, pages = {}, pmid = {26937070}, issn = {0960-1317}, support = {CC999999//Intramural CDC HHS/United States ; }, abstract = {Cell migration is one of the crucial steps in many physiological and pathological processes, including cancer development. Our recent studies have shown that carbon nanotubes (CNTs), similarly to asbestos, can induce accelerated cell growth and invasiveness that contribute to their mesothelioma pathogenicity. Malignant mesothelioma is a very aggressive tumor that develops from cells of the mesothelium, and is most commonly caused by exposure to asbestos. CNTs have a similar structure and mode of exposure to asbestos. This has raised a concern regarding the potential carcinogenicity of CNTs, especially in the pleural area which is a key target for asbestos-related diseases. In this paper, a static microfluidic gradient device was applied to study the migration of human pleural mesothelial cells which had been through a long-term exposure (4 months) to subcytotoxic concentration (0.02 μg cm[-2]) of single-walled CNTs (SWCNTs). Multiple migration signatures of these cells were investigated using the microfluidic gradient device for the first time. During the migration study, we observed that cell morphologies changed from flattened shapes to spindle shapes prior to their migration after their sensing of the chemical gradient. The migration of chronically SWCNT-exposed mesothelial cells was evaluated under different fetal bovine serum (FBS) concentration gradients, and the migration speeds and number of migrating cells were extracted and compared. The results showed that chronically SWCNT-exposed mesothelial cells are more sensitive to the gradient compared to non-SWCNT-exposed cells. The method described here allows simultaneous detection of cell morphology and migration under chemical gradient conditions, and also allows for real-time monitoring of cell motility that resembles in vivo cell migration. This platform would be much needed for supporting the development of more physiologically relevant cell models for better assessment and characterization of the mesothelioma hazard posed by nanomaterials.}, } @article {pmid26935421, year = {2016}, author = {Kadariya, Y and Menges, CW and Talarchek, J and Cai, KQ and Klein-Szanto, AJ and Pietrofesa, RA and Christofidou-Solomidou, M and Cheung, M and Mossman, BT and Shukla, A and Testa, JR}, title = {Inflammation-Related IL1β/IL1R Signaling Promotes the Development of Asbestos-Induced Malignant Mesothelioma.}, journal = {Cancer prevention research (Philadelphia, Pa.)}, volume = {9}, number = {5}, pages = {406-414}, pmid = {26935421}, issn = {1940-6215}, support = {R01 ES021110/ES/NIEHS NIH HHS/United States ; R01 CA190542/CA/NCI NIH HHS/United States ; P30 ES013508/ES/NIEHS NIH HHS/United States ; P42 ES023720/ES/NIEHS NIH HHS/United States ; P30 CA006927/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Apoptosis Regulatory Proteins/deficiency ; Asbestos/adverse effects ; CARD Signaling Adaptor Proteins ; Disease Models, Animal ; Humans ; Immunoblotting ; Immunohistochemistry ; Inflammation/*metabolism/*pathology ; Interleukin-1beta/*metabolism ; Lung Neoplasms/metabolism/*pathology ; Mesothelioma/metabolism/*pathology ; Mesothelioma, Malignant ; Mice ; Mice, Knockout ; Receptors, Interleukin-1/*metabolism ; Signal Transduction/physiology ; }, abstract = {Exposure to asbestos is causally associated with the development of malignant mesothelioma, a cancer of cells lining the internal body cavities. Malignant mesothelioma is an aggressive cancer resistant to all current therapies. Once inhaled or ingested, asbestos causes inflammation in and around tissues that come in contact with these carcinogenic fibers. Recent studies suggest that inflammation is a major contributing factor in the development of many types of cancer, including malignant mesothelioma. The NALP3/NLRP3 inflammasome, including the component ASC, is thought to be an important mediator of inflammation in cells that sense extracellular insults, such as asbestos, and activate a signaling cascade resulting in release of mature IL1β and recruitment of inflammatory cells. To determine if inflammasome-mediated inflammation contributes to asbestos-induced malignant mesothelioma, we chronically exposed Asc-deficient mice and wild-type littermates to asbestos and evaluated differences in tumor incidence and latency. The Asc-deficient mice showed significantly delayed tumor onset and reduced malignant mesothelioma incidence compared with wild-type animals. We also tested whether inflammation-related release of IL1β contributes to tumor development in an accelerated mouse model of asbestos-induced malignant mesothelioma. Nf2(+/-);Cdkn2a(+/-) mice exposed to asbestos in the presence of anakinra, an IL1 receptor (IL1R) antagonist, showed a marked delay in the median time of malignant mesothelioma onset compared with similarly exposed mice given vehicle control (33.1 weeks vs. 22.6 weeks, respectively). Collectively, these studies provide evidence for a link between inflammation-related IL1β/IL1R signaling and the development of asbestos-induced malignant mesothelioma. Furthermore, these findings provide rationale for chemoprevention strategies targeting IL1β/IL1R signaling in high-risk, asbestos-exposed populations. Cancer Prev Res; 9(5); 406-14. ©2016 AACR.}, } @article {pmid26934117, year = {2016}, author = {Roggli, VL}, title = {Fiber analysis vignettes: Electron microscopy to the rescue!.}, journal = {Ultrastructural pathology}, volume = {40}, number = {3}, pages = {126-133}, doi = {10.3109/01913123.2016.1149531}, pmid = {26934117}, issn = {1521-0758}, mesh = {Asbestos/*analysis ; Asbestosis/*diagnosis ; Electron Probe Microanalysis/*methods ; Humans ; Mesothelioma/etiology ; }, abstract = {There has been considerable interest in the exposure doses that contribute to the various asbestos-associated diseases. Epidemiological studies have shown important differences in the contributions of the various fiber types to asbestos-related diseases, with the amphiboles showing a greater degree of potency as compared to chrysotile. However, epidemiological studies have occasionally provided misleading results. Over the past several decades, there have been several examples where fiber analysis using electron microscopy produced unexpected results which were important to our understanding of disease-exposure relationships. It is the purpose of this article to summarize these fiber analysis vignettes.}, } @article {pmid26933413, year = {2016}, author = {Furukawa, M and Tao, H and Tanaka, T and Onoda, H and Murakami, T and Okabe, K}, title = {Chondrosarcoma of the Rib Mimicking Malignant Pleural Mesothelioma.}, journal = {Case reports in oncology}, volume = {9}, number = {1}, pages = {11-14}, pmid = {26933413}, issn = {1662-6575}, abstract = {A 62-year-old man with a history of long-term asbestos exposure was found to have a chest wall tumor invading the sixth rib on chest computed tomography. The computed tomography also revealed multiple plaques in the pleura. Malignant pleural mesothelioma was suspected, and thoracoscopic surgery was performed. Thoracoscopy revealed that the tumor location was extrapleural. Thus, excisional biopsy was performed. The tumor was histologically diagnosed as chondrosarcoma. Additional wide resection of the chest wall, including the fifth, sixth, and seventh ribs, was performed. Chest wall reconstruction was performed with a polypropylene mesh.}, } @article {pmid26931176, year = {2016}, author = {Toyokuni, S}, title = {The origin and future of oxidative stress pathology: From the recognition of carcinogenesis as an iron addiction with ferroptosis-resistance to non-thermal plasma therapy.}, journal = {Pathology international}, volume = {66}, number = {5}, pages = {245-259}, doi = {10.1111/pin.12396}, pmid = {26931176}, issn = {1440-1827}, mesh = {Animals ; Carcinogenesis/*metabolism/pathology ; Disease Models, Animal ; Humans ; Iron/*metabolism ; Oxidative Stress/*physiology ; Rats ; }, abstract = {Helmut Sies established the concept of oxidative stress in 1985. However, it took some time to introduce this concept into pathology, where investigators count on formalin-fixed paraffin-embedded tissue sections. I sought out antigens for this purpose based on an oxidative stress-induced rat renal carcinogenesis model, which revealed that 8-hydroxy-2'-deoxyguanosine and 4-hydroxy-2-nonenal-modified proteins are ideal. These two monoclonal antibodies successfully revealed the involvement of oxidative stress in numerous human diseases, including carcinogenesis and atherosclerosis. Shigeru Okada established the aforementioned ferric nitrilotriacetate (Fe-NTA)-induced rat renal carcinogenesis model, which thus far has answered many questions regarding the presence of target genes in oxidative stress-induced carcinogenesis and the sites that are susceptible to oxidative stress in the genome. Particularly, the similarity of genomic alterations between Fe-NTA-induced renal cancer and human cancers suggests that excess iron plays a role also in human carcinogenesis. Furthermore, excess iron is a major pathology in asbestos-induced mesothelioma, including chrysotile. Despite an analogy to asbestos, multi-wall carbon nanotubes were distinct in that diameter is another responsible factor for mesothelial carcinogenesis. Recently, non-thermal plasma emerged as a candidate for medical intervention for wounds and cancers via manipulating oxidative stress. Counteracting excess iron is a promising preventive strategy for major diseases.}, } @article {pmid26914008, year = {2015}, author = {Soberg, MJ and van Zandwijk, N}, title = {Incidence of malignant mesothelioma in New Zealand and Australia: a global snapshot.}, journal = {The New Zealand medical journal}, volume = {128}, number = {1427}, pages = {68-71}, pmid = {26914008}, issn = {1175-8716}, mesh = {Australia/epidemiology ; Humans ; Incidence ; Lung Neoplasms/*epidemiology ; Mesothelioma/*epidemiology ; Mesothelioma, Malignant ; New Zealand/epidemiology ; }, } @article {pmid26904248, year = {2016}, author = {Nakano, T and Endo, S and Tetsuka, K and Fukushima, N}, title = {Asymptomatic localized pleural amyloidosis mimicking malignant pleural mesothelioma: report of a case.}, journal = {Journal of thoracic disease}, volume = {8}, number = {1}, pages = {E157-60}, pmid = {26904248}, issn = {2072-1439}, abstract = {We herein report an asymptomatic 65-year-old male with localized pleural amyloidosis mimicking malignant pleural mesothelioma. He had a history of exposure to asbestos and was admitted for investigation of an abnormal pleural thickness detected by chest radiography. Positron emission tomography showed elevation of standardized uptake value corresponding to the pleural thickness. Partial pleurectomy including the tumor was performed for the purpose of diagnosis and local disease control. The pathological examination showed that the tumor was pleural amyloidosis. The tumor was diagnosed as localized primary amyloidosis, because serum monoclonal protein concentration did not increase. Pleural amyloidosis should be considered as a differential diagnosis from pleural mesothelioma.}, } @article {pmid26903779, year = {2016}, author = {Morré, DJ and Hostetler, B and Taggart, DJ and Morré, DM and Musk, AW and Robinson, BW and Creaney, J}, title = {Erratum to: ENOX2-based early detection (ONCOblot) of asbestos-induced malignant mesothelioma 4-10 years in advance of clinical symptoms.}, journal = {Clinical proteomics}, volume = {13}, number = {}, pages = {3}, pmid = {26903779}, issn = {1542-6416}, abstract = {[This corrects the article DOI: 10.1186/s12014-016-9103-3.].}, } @article {pmid26900461, year = {2016}, author = {Vazquez, MV and Selvendran, S and Cheluvappa, R and McKay, MJ}, title = {Peritoneal mesothelioma metastasis to the tongue - Comparison with 8 pleural mesothelioma reports with tongue metastases.}, journal = {Annals of medicine and surgery (2012)}, volume = {5}, number = {}, pages = {101-105}, pmid = {26900461}, issn = {2049-0801}, abstract = {PURPOSE: Malignant mesothelioma (MM) rarely arises from the peritoneum. We describe the 1st such case which metastasised to the head and neck region (tongue).

METHODS: We briefly surveyed the American Surveillance Epidemiology and End Results (SEER) database, and the British Cancer Research UK database for the latest trends in MM incidence. We did a systematic Pubmed search for other MM reports with tongue metastases.

American and British data show that MM incidence in men has stabilised in the last 10 years, earlier than previously predicted. The tongue is an unusual site for MM spread, with ours being only the 9th such case described. Our summary of published cases of MM metastasising to the tongue brings out our patient to be the least in age(35 years), and the only one to have peritoneal MM as the primary. Seven of the 9 cases were male. Only 2 had a recorded history of exposure to asbestos. All 9 patients had the epithelioid subtype of MM. Surgery was done as the exclusive reported intervention in 4 out of the 9 patients. Only 2 cases received radiotherapy, amongst whom, only our patient responded.

CONCLUSIONS: Metastasis of MM to the tongue is rare and usually in the uncommon context of MM with multiple sites of extra-thoracic or extra-abdominal spread. We have described a unique clinical manifestation of a rare subtype of mesothelioma. Moreover, we have tabulated and summarised details (including responses to surgery or/and radiotherapy) regarding all reported cases of mesotheliomas with tongue metastasis.}, } @article {pmid26896281, year = {2016}, author = {Kadariya, Y and Cheung, M and Xu, J and Pei, J and Sementino, E and Menges, CW and Cai, KQ and Rauscher, FJ and Klein-Szanto, AJ and Testa, JR}, title = {Bap1 Is a Bona Fide Tumor Suppressor: Genetic Evidence from Mouse Models Carrying Heterozygous Germline Bap1 Mutations.}, journal = {Cancer research}, volume = {76}, number = {9}, pages = {2836-2844}, pmid = {26896281}, issn = {1538-7445}, support = {P30 CA010815/CA/NCI NIH HHS/United States ; R01 CA175691/CA/NCI NIH HHS/United States ; P30 ES013508/ES/NIEHS NIH HHS/United States ; P42 ES023720/ES/NIEHS NIH HHS/United States ; P30 CA006927/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Comparative Genomic Hybridization ; Disease Models, Animal ; Gene Knock-In Techniques ; *Genes, Tumor Suppressor ; Genetic Predisposition to Disease/genetics ; Genotype ; *Germ-Line Mutation ; Heterozygote ; Immunohistochemistry ; Laser Capture Microdissection ; Mice ; Mice, Knockout ; *Neoplastic Syndromes, Hereditary ; Reverse Transcriptase Polymerase Chain Reaction ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {Individuals harboring inherited heterozygous germline mutations in BAP1 are predisposed to a range of benign and malignant tumor types, including malignant mesothelioma, melanoma, and kidney carcinoma. However, evidence to support a tumor-suppressive role for BAP1 in cancer remains contradictory. To test experimentally whether BAP1 behaves as a tumor suppressor, we monitored spontaneous tumor development in three different mouse models with germline heterozygous mutations in Bap1, including two models in which the knock-in mutations are identical to those reported in human BAP1 cancer syndrome families. We observed spontaneous malignant tumors in 54 of 93 Bap1-mutant mice (58%) versus 4 of 43 (9%) wild-type littermates. All three Bap1-mutant models exhibited a high incidence and similar spectrum of neoplasms, including ovarian sex cord stromal tumors, lung and mammary carcinomas, and spindle cell tumors. Notably, we also observed malignant mesotheliomas in two Bap1-mutant mice, but not in any wild-type animals. We further confirmed that the remaining wild-type Bap1 allele was lost in both spontaneous ovarian tumors and mesotheliomas, resulting in the loss of Bap1 expression. Additional studies revealed that asbestos exposure induced a highly significant increase in the incidence of aggressive mesotheliomas in the two mouse models carrying clinically relevant Bap1 mutations compared with asbestos-exposed wild-type littermates. Collectively, these findings provide genetic evidence that Bap1 is a bona fide tumor suppressor gene and offer key insights into the contribution of carcinogen exposure to enhanced cancer susceptibility. Cancer Res; 76(9); 2836-44. ©2016 AACR.}, } @article {pmid26894775, year = {2016}, author = {Hispán, P and Pascual, JC and González, I and Bravo, D and Peiró, G}, title = {Cutaneous Metastases From Malignant Mesothelioma of the Tunica Vaginalis Testis.}, journal = {The American Journal of dermatopathology}, volume = {38}, number = {3}, pages = {222-225}, doi = {10.1097/DAD.0000000000000369}, pmid = {26894775}, issn = {1533-0311}, mesh = {Aged, 80 and over ; Asbestos/adverse effects ; Biomarkers, Tumor/analysis ; Fatal Outcome ; Humans ; Immunohistochemistry ; Lung Neoplasms/*secondary ; Male ; Mesothelioma/*secondary ; Mesothelioma, Malignant ; Skin Neoplasms/*secondary ; Testicular Neoplasms/*pathology ; }, abstract = {Mesotheliomas are uncommon tumors arising from mesothelial cells lining the serous membranes of the pleura, pericardium, peritoneum, and tunica vaginalis testis. Less than 100 cases arising from the tunica vaginalis testis have been published and, to our knowledge, only 5 cases of cutaneous involvement from these tumors have been reported. We report an additional case with fatal outcome. A 93-year-old man presented with multiple polypoid nodules on the left scrotum. Ulceration was also present, and a firm 5-cm palpable testicular mass was also found. The patient had been exposed to asbestos for 40 years. Histologic examination of a skin biopsy from one of the nodules showed diffuse dermal infiltration of markedly atypical cuboidal cells, with polymorphous and hyperchromatic nuclei. Mitotic figures were common. These cuboidal cells lined clefts, forming a tubular and micropapillary pattern throughout papillary and reticular dermis. Immunohistochemical study showed strong nuclear and cytoplasmic positivity for calretinin, epithelial membrane antigen (cytoplasmic), and cytokeratin-7 (cytoplasmic) and nuclear positivity for Wilms tumor-1. These findings were consistent with cutaneous infiltration from malignant mesothelioma of the tunica vaginalis testis. Treatment of this rare tumor remains challenging because there are currently no recommended guidelines, but radical inguinal orchiectomy is an optimal choice.}, } @article {pmid26893272, year = {2016}, author = {Berardi, R and Fiordoliva, I and De Lisa, M and Ballatore, Z and Caramanti, M and Morgese, F and Savini, A and Rinaldi, S and Torniai, M and Tiberi, M and Ferrini, C and Onofri, A and Cascinu, S}, title = {Clinical and pathologic predictors of clinical outcome of malignant pleural mesothelioma.}, journal = {Tumori}, volume = {102}, number = {2}, pages = {190-195}, doi = {10.5301/tj.5000418}, pmid = {26893272}, issn = {2038-2529}, mesh = {Adult ; Aged ; Anemia/blood/*diagnosis/etiology ; Antineoplastic Agents/*therapeutic use ; CA-125 Antigen/blood ; Disease-Free Survival ; Female ; Hemoglobins/*metabolism ; Humans ; Italy/epidemiology ; Kaplan-Meier Estimate ; Karnofsky Performance Status ; Lung Neoplasms/*mortality/*pathology/therapy ; Male ; Mesothelioma/*mortality/*pathology/therapy ; Mesothelioma, Malignant ; Middle Aged ; Pemetrexed/administration & dosage ; Platinum Compounds/administration & dosage ; Pleural Neoplasms/*mortality/*pathology/therapy ; Predictive Value of Tests ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Treatment Outcome ; }, abstract = {AIMS AND BACKGROUND: Although worldwide use of asbestos has decreased, the incidence of malignant pleural mesothelioma (MPM) is expected to increase over the next few decades. A number of scoring systems has been proposed to assess clinicopathologic features and to predict the prognosis. We assessed the relationship between patients' features and disease evolution in order to choose the best treatment able to prolong overall survival (OS) and progression-free survival (PFS).

METHODS: We retrospectively analyzed patients with locally advanced or metastatic MPM, treated at the Department of Medical Oncology, Università Politecnica Marche, Italy, from January 2003 to September 2013. Data on age, sex, smoking history, asbestos exposure, performance status, tumor stage, histology, type of treatment, and routine laboratory tests including complete blood count panel, date of death, or censored status were collected. The OS and PFS were estimated using Kaplan-Meier method and Cox analysis was performed to analyze the prognostic relevance of clinical parameters.

RESULTS: We enrolled a total of 62 patients. Univariate analysis showed that histologic type, performance status, response to first-line therapy, pretreatment hemoglobin levels, and plasmatic Ca125 were significant prognostic factors. Conversely, no significant correlation was found between age, sex, smoking history, reported exposure to asbestos, stages at diagnosis, treatments, and OS and PFS.

CONCLUSIONS: Our results showed that anemia and increased Ca125 might be considered negative prognostic parameters in MPM patients and confirmed the prognostic role of histotype, performance status, and response to first-line chemotherapy.}, } @article {pmid26891694, year = {2016}, author = {Chernova, T and Sun, XM and Powley, IR and Galavotti, S and Grosso, S and Murphy, FA and Miles, GJ and Cresswell, L and Antonov, AV and Bennett, J and Nakas, A and Dinsdale, D and Cain, K and Bushell, M and Willis, AE and MacFarlane, M}, title = {Molecular profiling reveals primary mesothelioma cell lines recapitulate human disease.}, journal = {Cell death and differentiation}, volume = {23}, number = {7}, pages = {1152-1164}, pmid = {26891694}, issn = {1476-5403}, support = {MC_EX_G0902052/MRC_/Medical Research Council/United Kingdom ; MC_U132685863/MRC_/Medical Research Council/United Kingdom ; MC_UP_A600_1023/MRC_/Medical Research Council/United Kingdom ; MC_UP_A600_1024/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Aged ; Cyclin-Dependent Kinase Inhibitor p16/genetics/metabolism ; Cyclin-Dependent Kinase Inhibitor p18/genetics/metabolism ; Female ; Genomic Instability ; Humans ; Lung Neoplasms/*metabolism/pathology ; Male ; Mesothelioma/*metabolism/pathology ; Mesothelioma, Malignant ; *Metabolome ; Middle Aged ; Neurofibromin 2/genetics/metabolism ; Oxygen Consumption ; Principal Component Analysis ; Tandem Repeat Sequences ; Transcriptome ; Tumor Cells, Cultured ; Tumor Suppressor Protein p14ARF/genetics/metabolism ; Tumor Suppressor Protein p53/genetics/metabolism ; Up-Regulation ; }, abstract = {Malignant mesothelioma (MM) is an aggressive, fatal tumor strongly associated with asbestos exposure. There is an urgent need to improve MM patient outcomes and this requires functionally validated pre-clinical models. Mesothelioma-derived cell lines provide an essential and relatively robust tool and remain among the most widely used systems for candidate drug evaluation. Although a number of cell lines are commercially available, a detailed comparison of these commercial lines with freshly derived primary tumor cells to validate their suitability as pre-clinical models is lacking. To address this, patient-derived primary mesothelioma cell lines were established and characterized using complementary multidisciplinary approaches and bioinformatic analysis. Clinical markers of mesothelioma, transcriptional and metabolic profiles, as well as the status of p53 and the tumor suppressor genes CDKN2A and NF2, were examined in primary cell lines and in two widely used commercial lines. Expression of MM-associated markers, as well as the status of CDKN2A, NF2, the 'gatekeeper' in MM development, and their products demonstrated that primary cell lines are more representative of the tumor close to its native state and show a degree of molecular diversity, thus capturing the disease heterogeneity in a patient cohort. Molecular profiling revealed a significantly different transcriptome and marked metabolic shift towards a greater glycolytic phenotype in commercial compared with primary cell lines. Our results highlight that multiple, appropriately characterised, patient-derived tumor cell lines are required to enable concurrent evaluation of molecular profiles versus drug response. Furthermore, application of this approach to other difficult-to-treat tumors would generate improved cellular models for pre-clinical evaluation of novel targeted therapies.}, } @article {pmid26889976, year = {2016}, author = {Kao, SC and Kirschner, MB and Cooper, WA and Tran, T and Burgers, S and Wright, C and Korse, T and van den Broek, D and Edelman, J and Vallely, M and McCaughan, B and Pavlakis, N and Clarke, S and Molloy, MP and van Zandwijk, N and Reid, G}, title = {A proteomics-based approach identifies secreted protein acidic and rich in cysteine as a prognostic biomarker in malignant pleural mesothelioma.}, journal = {British journal of cancer}, volume = {114}, number = {5}, pages = {524-531}, pmid = {26889976}, issn = {1532-1827}, mesh = {Animals ; Biomarkers, Tumor/*metabolism ; Cell Line, Tumor ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Immunohistochemistry ; Lung Neoplasms/*metabolism/pathology ; Male ; Mass Spectrometry ; Mesothelioma/*metabolism/pathology ; Mesothelioma, Malignant ; Mice ; Middle Aged ; Multivariate Analysis ; Neoplasm Transplantation ; Osteonectin/*metabolism ; Pleural Neoplasms/*metabolism/pathology ; Prognosis ; Proportional Hazards Models ; Proteomics ; Retrospective Studies ; Survival Rate ; Tissue Array Analysis ; }, abstract = {BACKGROUND: We aimed to identify prognostic blood biomarkers using proteomics-based approaches in malignant pleural mesothelioma (MPM).

METHODS: Plasma samples from 12 MPM patients were used for exploratory mass spectrometry and ELISA analyses. The significance of secreted protein acidic and rich in cysteine (SPARC) was examined in sera from a Dutch series (n=97). To determine the source of the circulating SPARC, we investigated SPARC expression in MPM tumours and healthy controls, as well as the expression and secretion from cell lines and xenografts.

RESULTS: Secreted protein acidic and rich in cysteine was identified as a putative prognostic marker in plasma. Validation in the Dutch series showed that the median survival was higher in patients with low SPARC compared with those with high SPARC (19.0 vs 8.8 months; P=0.01). In multivariate analyses, serum SPARC remained as an independent predictor (HR 1.55; P=0.05). In MPM tumour samples, SPARC was present in the tumour cells and stromal fibroblasts. Cellular SPARC expression was higher in 5 out of 7 cell lines compared with two immortalized mesothelial lines. Neither cell lines nor xenograft tumours secreted detectable SPARC.

CONCLUSIONS: Low circulating SPARC was associated with favourable prognosis. Secreted protein acidic and rich in cysteine was present in both tumour cells and stromal fibroblasts; and our in vitro and in vivo experiments suggest that stromal fibroblasts are a potential source of circulating SPARC.}, } @article {pmid26889212, year = {2016}, author = {Miozzi, E and Rapisarda, V and Marconi, A and Costa, C and Polito, I and Spandidos, DA and Libra, M and Fenga, C}, title = {Fluoro-edenite and carbon nanotubes: The health impact of 'asbestos-like' fibres.}, journal = {Experimental and therapeutic medicine}, volume = {11}, number = {1}, pages = {21-27}, pmid = {26889212}, issn = {1792-0981}, abstract = {Several decades have passed since Wagner et al demonstrated a causal link between asbestos fibre inhalation and the development of pleural mesothelioma in 1960. It was later suggested that pleural plaques are a benign consequence of exposure to these fibres. Most recently, a significant association between exposure to asbestos and cancer diagnosed at various sites, such as the peritoneum, stomach, pharynx, colon and ovaries has been demonstrated. The great concerns about public health that arose from the scientific evidence presented above have led to the banning of asbestos in several countries. Over the years, the suspicion that particles with a high aspect ratio may have asbestos-like pathogenicity has been supported by increasing evidence. Natural occurring minerals, as well as man-made fibres, have proven capable of inducing either chronic inflammation of serous membranes, or, in some cases, the development of peritoneal and pleural mesothelioma. The pathogenic role of both fluoro-edenite and carbon nanotubes, two 'asbestos-like' fibres is summarized and discussed in this review. The data presented herein support the notion that occupational exposure to these two types of fibre contributes to the development of different types of cancer.}, } @article {pmid26887267, year = {2015}, author = {Jiang, Z and Chen, J and Lou, J and Miao, C and Shao, D and Zhang, X}, title = {[Monitoring and analysis of asbestos concentration in working environment of different asbestos-producing technologies in a certain area].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {33}, number = {11}, pages = {833-837}, pmid = {26887267}, issn = {1001-9391}, mesh = {Asbestos/*analysis ; Asbestos, Crocidolite/analysis ; Asbestos, Serpentine/analysis ; China/epidemiology ; Dust/analysis ; Humans ; Lung Neoplasms/epidemiology ; Mesothelioma/epidemiology ; Mesothelioma, Malignant ; Occupational Diseases/epidemiology ; Silicon Dioxide/analysis ; *Workplace ; }, abstract = {OBJECTIVE: To analyze asbestos exposure level between 1984 and 2010 in a district of malignant mesothelioma with clustering incidence in Zhejiang Province, in order to improve the recognizing and early diagnosis of malignant mesothelioma, protect the health of workers.

METHODS: Monitoring data of total asbestos dust concentration in the air of workplace from 1984 to 2010 in asbestos textile enterprises, family hand spinning operation, brake production, and asbestos board production in Zhejiang Province were collected in the local CDC. A total of 766 TWA copies of mass concentration were collected, and 1233 copies of MAC data. Asbestos mass concentration and fibre counting concentration of 29 points of family hand spinning operation were parallel determinated in the same time and the same sampling point. Raw asesbtos materials and dust composition of local asbestos processing corporations were collected and analyzed using X-ray diffraction method.

RESULTS: Raw materials of asbestos used between 1984 and 2010 in this area were chrysotile from Sichuan, Qinghai, Xinjiang, Russia, Zimbabwe, and some were mixed with SiO2, CaCO3 and other impurities. Raw materials used in asbestos board production were blue asbestos. Dust concentration between 1960s and 1980s in asbestos processing plants far exceeded the national standard. After then the dust concentration decreased significantly, but still higher than the national standard. 95.2% of air dust concentrations in the workplaces of asbestos factories exceeded the standard, and dust concentrations of workplaces of raw material, spinning, weaving, carding and labor insurance were above 90% in which carding work had the highest median concentration. 37.9% of dust mass concentrations in hand spinning work exceeded the standard where textile machinery side had the highest value. Beating job in asbestos board manufacturing and grinding job in brake production had higher concentrations.

CONCLUSIONS: Most of production technologies in asbestos processing industry exceed the standard level, indicating that the workers were at risk for malignant mesothelioma and other asbestos related diseases, which should draw high attention.}, } @article {pmid26884050, year = {2016}, author = {Boffetta, P and La Vecchia, C}, title = {Setting new standards for epidemiological research on mesothelioma.}, journal = {Occupational and environmental medicine}, volume = {73}, number = {5}, pages = {289}, doi = {10.1136/oemed-2015-103479}, pmid = {26884050}, issn = {1470-7926}, mesh = {Asbestos ; *Asbestos, Amphibole ; Epidemiologic Studies ; Humans ; Lung ; Lung Neoplasms ; *Mesothelioma ; }, } @article {pmid26881550, year = {2015}, author = {Patra, A and Kundu, S and Pal, A and Saha, S}, title = {Mesothelioma with superior vena cava obstruction in young female following short latency of asbestos exposure.}, journal = {Journal of cancer research and therapeutics}, volume = {11}, number = {4}, pages = {940-942}, doi = {10.4103/0973-1482.160924}, pmid = {26881550}, issn = {1998-4138}, mesh = {Adolescent ; Asbestos/*adverse effects ; Carcinogens/*pharmacology ; Female ; Humans ; Mesothelioma/chemically induced/*pathology ; Pleural Effusion ; Pleural Neoplasms/chemically induced/*pathology ; Superior Vena Cava Syndrome/chemically induced/*pathology ; Tomography, X-Ray Computed ; }, abstract = {An 18 years female was admitted with right-sided chest pain, dry cough, and low-grade fever and weight loss for last 1 month. On examination, patient had features of superior vena cava (SVC) syndrome with right-sided pleural effusion. Chest X-ray showed mediastinal widening with nonhomogenous opacity mainly in the periphery of right upper and mid zone with right-sided pleural effusion. Ultrasonography thorax confirmed mild pleural effusion. Pleural fluid analysis showed lymphocytic, exudative, low adenosine deaminase with negative for Pap smear. Contrast-enhanced computed tomography (CT) thorax revealed large extensive nodular soft tissue lesion along right mediastinum as well as costal pleura, with enlarged pretracheal lymphadenopathy and SVC obstruction. CT guided Tru-cut biopsy report came as malignant epithelial tumor with polygonal shape, abundant eosinophilic cytoplasm and nuclei with prominent nucleoli suggestive of mesothelioma of epithelioid type. The tumor cell expressed calretinin, WT-1, and immunonegative for thyroid transcription factor-1.}, } @article {pmid26867567, year = {2016}, author = {Morgan, R and Simpson, G and Gray, S and Gillett, C and Tabi, Z and Spicer, J and Harrington, KJ and Pandha, HS}, title = {HOX transcription factors are potential targets and markers in malignant mesothelioma.}, journal = {BMC cancer}, volume = {16}, number = {}, pages = {85}, pmid = {26867567}, issn = {1471-2407}, mesh = {Animals ; Apoptosis/drug effects ; Cell Line, Tumor ; DNA-Binding Proteins/genetics/*metabolism ; Gene Expression Regulation, Neoplastic/drug effects ; Homeodomain Proteins/*biosynthesis/genetics/metabolism ; Humans ; Intercellular Signaling Peptides and Proteins ; Lung Neoplasms/drug therapy/*genetics/pathology ; Mesothelioma/drug therapy/*genetics/pathology ; Mesothelioma, Malignant ; Mice ; Peptides/*administration & dosage ; Pre-B-Cell Leukemia Transcription Factor 1 ; Proto-Oncogene Proteins/genetics/*metabolism ; Transcription Factors/*biosynthesis/genetics/metabolism ; Xenograft Model Antitumor Assays ; }, abstract = {BACKGROUND: The HOX genes are a family of homeodomain-containing transcription factors that determine cellular identity during development and which are dys-regulated in some cancers. In this study we examined the expression and oncogenic function of HOX genes in mesothelioma, a cancer arising from the pleura or peritoneum which is associated with exposure to asbestos.

METHODS: We tested the sensitivity of the mesothelioma-derived lines MSTO-211H, NCI-H28, NCI-H2052, and NCI-H226 to HXR9, a peptide antagonist of HOX protein binding to its PBX co-factor. Apoptosis was measured using a FACS-based assay with Annexin, and HOX gene expression profiles were established using RT-QPCR on RNA extracted from cell lines and primary mesotheliomas. The in vivo efficacy of HXR9 was tested in a mouse MSTO-211H flank tumor xenograft model.

RESULTS: We show that HOX genes are significantly dysregulated in malignant mesothelioma. Targeting HOX genes with HXR9 caused apoptotic cell death in all of the mesothelioma-derived cell lines, and prevented the growth of mesothelioma tumors in a mouse xenograft model. Furthermore, the sensitivity of these lines to HXR9 correlated with the relative expression of HOX genes that have either an oncogenic or tumor suppressive function in cancer. The analysis of HOX expression in primary mesothelioma tumors indicated that these cells could also be sensitive to the disruption of HOX activity by HXR9, and that the expression of HOXB4 is strongly associated with overall survival.

CONCLUSION: HOX genes are a potential therapeutic target in mesothelioma, and HOXB4 expression correlates with overall survival.}, } @article {pmid26860323, year = {2016}, author = {Farioli, A and Ottone, M and Morganti, AG and Compagnone, G and Romani, F and Cammelli, S and Mattioli, S and Violante, FS}, title = {Radiation-induced mesothelioma among long-term solid cancer survivors: a longitudinal analysis of SEER database.}, journal = {Cancer medicine}, volume = {5}, number = {5}, pages = {950-959}, pmid = {26860323}, issn = {2045-7634}, mesh = {Adult ; Aged ; Aged, 80 and over ; Dose-Response Relationship, Radiation ; Female ; Humans ; Incidence ; Longitudinal Studies ; Male ; Mesothelioma/epidemiology/*etiology ; Middle Aged ; Neoplasms/epidemiology/radiotherapy ; Neoplasms, Radiation-Induced/epidemiology/*etiology ; Neoplasms, Second Primary/epidemiology/*etiology ; Peritoneal Neoplasms/epidemiology/*etiology ; Pleural Neoplasms/epidemiology/*etiology ; Radiotherapy/adverse effects ; SEER Program ; Survivors/statistics & numerical data ; United States/epidemiology ; Young Adult ; }, abstract = {We investigated the association between external beam radiotherapy (EBRT) and pleural and peritoneal mesothelioma among long-term (>5 years) solid cancer survivors. We analyzed data from the US Surveillance, Epidemiology, and End Results (SEER) program (1973-2012). We fitted survival models adjusted by age, gender, race, year, surgery, and relative risk of primary mesothelioma in the county of residence (proxy for individual asbestos exposure). We estimated hazard ratios [HR] with reference to nonirradiated patients. We distinguished between scattered and direct irradiation to study the dose-response. We observed 301 mesotheliomas (265 pleural; 32 peritoneal; 4 others) among 935,637 patients. EBRT increased the risk of mesothelioma (any site; HR 1.34, 95% CI 1.04-1.77). We observed an increased risk of pleural mesothelioma (HR for EBRT 1.34, 95% CI 1.01-1.77), but we did not find signs of a dose-response relationship (HR for scattered irradiation 1.38; HR for direct irradiation 1.23). On the opposite, only direct peritoneal irradiation was associated with peritoneal mesothelioma (HR 2.20, 95% CI 0.99-4.88), particularly for latencies ≥10 years (HR 3.28, 95% CI 1.14-9.43). A competing risks analysis revealed that the clinical impact of radiation-induced mesothelioma was limited by the high frequency of competing events. The cumulative incidence function of mesothelioma after 40 years of observation was very low (nonirradiated patients 0.00032, irradiated patients 0.00055).EBRT might be a determinant of mesothelioma. Longer latency periods are associated with higher risks, while the dose-response seems nonlinear. The clinical impact of mesothelioma after EBRT for primary solid cancers is limited.}, } @article {pmid26858099, year = {2016}, author = {Van der Bij, S and Vermeulen, RC and Portengen, L and Moons, KG and Koffijberg, H}, title = {Expected number of asbestos-related lung cancers in the Netherlands in the next two decades: a comparison of methods.}, journal = {Occupational and environmental medicine}, volume = {73}, number = {5}, pages = {342-349}, doi = {10.1136/oemed-2014-102614}, pmid = {26858099}, issn = {1470-7926}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Cohort Studies ; Environmental Exposure/*adverse effects ; Female ; Humans ; Lung Neoplasms/*chemically induced ; Male ; Mesothelioma/*chemically induced ; Middle Aged ; *Models, Biological ; Models, Statistical ; Netherlands ; Occupational Diseases/chemically induced ; Occupational Exposure/adverse effects ; Pleural Neoplasms/*chemically induced ; Risk Assessment ; Uncertainty ; }, abstract = {OBJECTIVES: Exposure to asbestos fibres increases the risk of mesothelioma and lung cancer. Although the vast majority of mesothelioma cases are caused by asbestos exposure, the number of asbestos-related lung cancers is less clear. This number cannot be determined directly as lung cancer causes are not clinically distinguishable but may be estimated using varying modelling methods.

METHODS: We applied three different modelling methods to the Dutch population supplemented with uncertainty ranges (UR) due to uncertainty in model input values. The first method estimated asbestos-related lung cancer cases directly from observed and predicted mesothelioma cases in an age-period-cohort analysis. The second method used evidence on the fraction of lung cancer cases attributable (population attributable risk (PAR)) to asbestos exposure. The third method incorporated risk estimates and population exposure estimates to perform a life table analysis.

RESULTS: The three methods varied substantially in incorporated evidence. Moreover, the estimated number of asbestos-related lung cancer cases in the Netherlands between 2011 and 2030 depended crucially on the actual method applied, as the mesothelioma method predicts 17 500 expected cases (UR 7000-57 000), the PAR method predicts 12 150 cases (UR 6700-19 000), and the life table analysis predicts 6800 cases (UR 6800-33 850).

CONCLUSIONS: The three different methods described resulted in absolute estimates varying by a factor of ∼2.5. These results show that accurate estimation of the impact of asbestos exposure on the lung cancer burden remains a challenge.}, } @article {pmid26855127, year = {2016}, author = {Ledda, C and Loreto, C and Pomara, C and Rapisarda, G and Fiore, M and Ferrante, M and Bracci, M and Santarelli, L and Fenga, C and Rapisarda, V}, title = {Sheep lymph-nodes as a biological indicator of environmental exposure to fluoro-edenite.}, journal = {Environmental research}, volume = {147}, number = {}, pages = {97-101}, doi = {10.1016/j.envres.2016.01.043}, pmid = {26855127}, issn = {1096-0953}, mesh = {Animals ; Asbestos, Amphibole/analysis/*toxicity ; *Environmental Exposure ; Environmental Monitoring ; Environmental Pollutants/*toxicity ; Lung/chemistry/pathology/ultrastructure ; Lymph Nodes/*chemistry/pathology/ultrastructure ; Lymphatic Diseases/chemically induced/pathology/*veterinary ; Microscopy, Electron, Scanning/veterinary ; *Sheep ; Sheep Diseases/chemically induced/*pathology ; Sicily ; }, abstract = {A significantly increased incidence of pleural mesothelioma in Biancavilla (Sicily, Italy) has been attributed to exposure to fluoro-edenite (FE), a fibrous amphibole extracted from a local stone quarry. The lymph-nodes draining the pulmonary lobes of sheep grazing around the town were examined, to gain insights into fibre diffusion. The pasture areas of six sheep flocks lying about 3km from Biancavilla were located using the global positioning system. The cranial tracheobronchial and one middle mediastinal lymph-node as well as four lung tissue samples were collected from 10 animals from each flock and from 10 control sheep for light and scanning electron microscopy (SEM) examination. The lymph-nodes from exposed sheep were enlarged and exhibited signs of anthracosis. Histologically, especially at the paracortical level, they showed lymph-follicle hyperplasia with large reactive cores and several macrophages (coniophages) containing grey-brownish particulate interspersed with elements with a fibril structure, forming aggregates of varying dimensions (coniophage nodules). Similar findings were detected in some peribronchiolar areas of the lung parenchyma. SEM examination showed that FE fibres measured 8-41µm in length and 0.4-1.39µm in diameter in both lymph-nodes and lung tissue. Monitoring of FE fibres in sheep lymph-nodes using appropriate techniques can help set up environmental pollution surveillance.}, } @article {pmid26853494, year = {2016}, author = {Borczuk, AC and Pei, J and Taub, RN and Levy, B and Nahum, O and Chen, J and Chen, K and Testa, JR}, title = {Genome-wide analysis of abdominal and pleural malignant mesothelioma with DNA arrays reveals both common and distinct regions of copy number alteration.}, journal = {Cancer biology & therapy}, volume = {17}, number = {3}, pages = {328-335}, pmid = {26853494}, issn = {1555-8576}, support = {CA-175691/CA/NCI NIH HHS/United States ; R01 CA175691/CA/NCI NIH HHS/United States ; R01 CA148805/CA/NCI NIH HHS/United States ; P30 ES013508/ES/NIEHS NIH HHS/United States ; P30 CA006927/CA/NCI NIH HHS/United States ; CA-06927/CA/NCI NIH HHS/United States ; }, mesh = {Abdominal Neoplasms/*genetics/pathology ; *DNA Copy Number Variations ; Genome-Wide Association Study ; Humans ; Lung Neoplasms/*genetics/pathology ; Mesothelioma/*genetics/pathology ; Mesothelioma, Malignant ; Mutation ; Peritoneal Neoplasms/*genetics/pathology ; Pleural Neoplasms/*genetics/pathology ; }, abstract = {Malignant mesothelioma (MM) is an aggressive tumor arising from mesothelial linings of the serosal cavities. Pleural space is the most common site, accounting for about 80% of cases, while peritoneum makes up the majority of the remaining 20%. While histologically similar, tumors from these sites are epidemiologically and clinically distinct and their attribution to asbestos exposure differs. We compared DNA array-based findings from 48 epithelioid peritoneal MMs and 41 epithelioid pleural MMs to identify similarities and differences in copy number alterations (CNAs). Losses in 3p (BAP1 gene), 9p (CDKN2A) and 22q (NF2) were seen in tumors from both tumor sites, although CDKN2A and NF2 losses were seen at a higher rate in pleural disease (p<0.01). Overall, regions of copy number gain were more common in peritoneal MM, whereas losses were more common in pleural MM, with regions of loss containing known tumor suppressor genes and regions of gain encompassing genes encoding receptor tyrosine kinase pathway members. Cases with known asbestos causation (n = 32) were compared with those linked to radiation exposure (n = 9). Deletions in 6q, 14q, 17p and 22q, and gain of 17q were seen in asbestos-associated but not radiation-related cases. As reported in post-radiation sarcoma, gains outnumbered losses in radiation-associated MM. The patterns of genomic imbalances suggest overlapping and distinct molecular pathways in MM of the pleura and peritoneum, and that differences in causation (i.e., asbestos vs. radiation) may account for some of these site-dependent differences.}, } @article {pmid26845122, year = {2016}, author = {Lee, D}, title = {Genetic Basis of Mesothelioma--More Than Asbestos Exposure.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {11}, number = {2}, pages = {e27-8}, doi = {10.1016/j.jtho.2015.09.005}, pmid = {26845122}, issn = {1556-1380}, mesh = {DNA, Neoplasm/*genetics ; Female ; Humans ; Lung Neoplasms/*genetics ; Male ; Mesothelioma/*genetics ; *Mutation ; Pleural Neoplasms/*genetics ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, } @article {pmid26845118, year = {2016}, author = {Billé, A and Krug, LM and Woo, KM and Rusch, VW and Zauderer, MG}, title = {Contemporary Analysis of Prognostic Factors in Patients with Unresectable Malignant Pleural Mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {11}, number = {2}, pages = {249-255}, pmid = {26845118}, issn = {1556-1380}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Lung Neoplasms/blood/drug therapy/*mortality ; Male ; Mesothelioma/blood/drug therapy/*mortality ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/blood/drug therapy/*mortality ; Prognosis ; Proportional Hazards Models ; }, abstract = {INTRODUCTION: Previous prognostic scoring systems for malignant pleural mesothelioma (MPM) included patients managed surgically and predated the use of pemetrexed. We analyzed prognostic factors in a contemporary cohort of patients with unresectable MPM who received pemetrexed-based chemotherapy.

METHODS: This single-institution analysis included patients with MPM who were managed nonsurgically from 2000 to 2013. Variables correlated with overall survival (OS) included sex, performance status (PS), asbestos exposure, tumor laterality, histology, clinical stage, initial positron emission tomography maximum standardized uptake value, hemoglobin level, platelet count, lymphocyte count, white cell and neutrophil counts, treatment type, and clinical benefit from treatment. OS was analyzed by the Kaplan-Meier method, and significance (p < 0.05) of prognostic factors was analyzed by the log-rank test and Cox regression.

RESULTS: A total of 191 patients met the study criteria: median age 71 years (range 46-90), 147 men (77%), 128 epithelioid tumors (67%), and 157 cases of stage III or IV MPM (82%). Median OS for all patients was 13.4 months. According to a univariate analysis, histology (p < 0.001), platelet count (< or = 450,000 versus >450,000, p < 0.001), initial PS (0-1 versus > or = 2), maximum standardized uptake value (< or = 8.1 versus >8.1, p = 0.037), and lymphocyte counts (p = 0.019) were associated with OS. According to a multivariable analysis, only histology, platelet count, and PS were independent prognostic factors. Epithelioid histology, PS, and elevated lymphocyte count at diagnosis were significantly associated with clinical benefit from first-line chemotherapy.

CONCLUSIONS: Our results confirm the significance of elements of the Cancer and Leukemia Group B and European Organisation for Research and Treatment of Cancer prognostic scoring systems, identify factors associated with clinical benefit from chemotherapy, and emphasize the impact of histology and clinical benefit of chemotherapy on outcomes.}, } @article {pmid26839332, year = {2016}, author = {Frank, EA and Carreira, VS and Birch, ME and Yadav, JS}, title = {Carbon Nanotube and Asbestos Exposures Induce Overlapping but Distinct Profiles of Lung Pathology in Non-Swiss Albino CF-1 Mice.}, journal = {Toxicologic pathology}, volume = {44}, number = {2}, pages = {211-225}, pmid = {26839332}, issn = {1533-1601}, support = {T32ES016646/ES/NIEHS NIH HHS/United States ; T42OH008432-07/OH/NIOSH CDC HHS/United States ; P30 ES006096/ES/NIEHS NIH HHS/United States ; 2P30ES006096-16A1/ES/NIEHS NIH HHS/United States ; T42OH008432/ACL/ACL HHS/United States ; T32 ES016646/ES/NIEHS NIH HHS/United States ; T42 OH008432/OH/NIOSH CDC HHS/United States ; }, mesh = {Alveolar Epithelial Cells/cytology/pathology ; Animals ; Apoptosis ; Asbestos, Crocidolite/*toxicity ; Histocytochemistry ; Inhalation Exposure/*analysis ; Lung/cytology/diagnostic imaging/*drug effects/pathology ; Male ; Mice ; Nanotubes, Carbon/*toxicity ; *Pneumonia/diagnostic imaging/pathology ; }, abstract = {Carbon nanotubes (CNTs) are emerging as important occupational and environmental toxicants owing to their increasing prevalence and potential to be inhaled as airborne particles. CNTs are a concern because of their similarities to asbestos, which include fibrous morphology, high aspect ratio, and biopersistence. Limitations in research models have made it difficult to experimentally ascertain the risk of CNT exposures to humans and whether these may lead to lung diseases classically associated with asbestos, such as mesothelioma and fibrosis. In this study, we sought to comprehensively compare profiles of lung pathology in mice following repeated exposures to multiwall CNTs or crocidolite asbestos (CA). We show that both exposures resulted in granulomatous inflammation and increased interstitial collagen; CA exposures caused predominantly bronchoalveolar hyperplasia, whereas CNT exposures caused alveolar hyperplasia of type II pneumocytes (T2Ps). T2Ps isolated from CNT-exposed lungs were found to have upregulated proinflammatory genes, including interleukin 1ß (IL-1ß), in contrast to those from CA exposed. Immunostaining in tissue showed that while both toxicants increased IL-1ß protein expression in lung cells, T2P-specific IL-1ß increases were greater following CNT exposure. These results suggest related but distinct mechanisms of action by CNTs versus asbestos which may lead to different outcomes in the 2 exposure types.}, } @article {pmid26836920, year = {2016}, author = {Thomas, R and Cheah, HM and Creaney, J and Turlach, BA and Lee, YC}, title = {Longitudinal Measurement of Pleural Fluid Biochemistry and Cytokines in Malignant Pleural Effusions.}, journal = {Chest}, volume = {149}, number = {6}, pages = {1494-1500}, doi = {10.1016/j.chest.2016.01.001}, pmid = {26836920}, issn = {1931-3543}, mesh = {Aged ; Aged, 80 and over ; Australia ; Blood Cell Count/methods ; Chemokine CCL2/analysis ; Cytokines/*analysis ; *Exudates and Transudates/immunology/metabolism ; Female ; Humans ; Longitudinal Studies ; *Lung Neoplasms/complications/pathology ; Male ; *Mesothelioma/complications/pathology ; Mesothelioma, Malignant ; Middle Aged ; *Pleural Effusion, Malignant/diagnosis/etiology/metabolism ; Tumor Necrosis Factor-alpha/analysis ; Vascular Endothelial Growth Factor A/analysis ; }, abstract = {BACKGROUND: Malignant pleural effusion (MPE) is common. Existing literature on pleural fluid compositions is restricted to cross-sectional sampling with little information on longitudinal changes of fluid biochemistry and cytokines with disease progression. Indwelling pleural catheters provide the unique opportunity for repeated sampling and longitudinal evaluation of MPE, which may provide insight into tumor pathobiology.

METHODS: We collected 638 MPE samples from 103 patients managed with indwelling pleural catheters over 95 days (median, range 0-735 days) and analyzed them for protein, pH, lactate dehydrogenase, and glucose levels. Peripheral blood was quantified for hematocrit, platelets, leukocytes, protein, and albumin. Cytokine levels (monocyte chemotactic protein [MCP]-1; vascular endothelial growth factor; interleukin-6, -8, and -10; tumor necrosis factor-α; and interferon-gamma) were determined in 298 samples from 35 patients with mesothelioma. Longitudinal changes of all parameters were analyzed using a linear mixed model.

RESULTS: Significant decreases were observed over time in pleural fluid protein by 8 g/L per 100 days (SE, 1.32; P < .0001) and pH (0.04/100 days; SE, 0.02; P = .0203), accompanied by a nonsignificant rise in lactate dehydrogenase. The ratio of pleural fluid to serum protein decreased by 0.06/100 days (SE, 0.02; P = .04). MPEs from mesothelioma (n = 63) had lower pleural fluid glucose (P = .0104) at baseline and a faster rate of decline in glucose (P = .0423) when compared with non-mesothelioma effusions (n = 38). A progressive rise in mesothelioma pleural fluid concentration of [log] MCP-1 ([log] 0.37 pg/mL per 100 days; SE, 0.13; P = .0046), but not of other cytokines, was observed.

CONCLUSIONS: MPE fluids become less exudative and more acidic over the disease course. The rise in MCP-1 levels suggests a pathobiological role in MPE.}, } @article {pmid26825970, year = {2016}, author = {Abakay, A and Tanrikulu, AC and Imamoglu, MS and Ayhan, M and Taylan, M and Kaplan, MA and Abakay, O}, title = {Erratum to: High-risk mesothelioma relation to meteorological and geological condition and distance from naturally occurring asbestos.}, journal = {Environmental health and preventive medicine}, volume = {21}, number = {2}, pages = {91}, doi = {10.1007/s12199-016-0508-4}, pmid = {26825970}, issn = {1347-4715}, } @article {pmid26824986, year = {2016}, author = {Kang, HC and Kim, HK and Lee, S and Mendez, P and Kim, JW and Woodard, G and Yoon, JH and Jen, KY and Fang, LT and Jones, K and Jablons, DM and Kim, IJ}, title = {Whole exome and targeted deep sequencing identify genome-wide allelic loss and frequent SETDB1 mutations in malignant pleural mesotheliomas.}, journal = {Oncotarget}, volume = {7}, number = {7}, pages = {8321-8331}, pmid = {26824986}, issn = {1949-2553}, mesh = {Blotting, Western ; Exome/*genetics ; Female ; Genome, Human ; High-Throughput Nucleotide Sequencing/*methods ; Histone-Lysine N-Methyltransferase ; Humans ; Immunoenzyme Techniques ; Loss of Heterozygosity/*genetics ; Lung Neoplasms/*genetics ; Mesothelioma/*genetics ; Mesothelioma, Malignant ; Middle Aged ; Mutation/*genetics ; Pleural Neoplasms/*genetics ; Prognosis ; Protein Methyltransferases/*genetics ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Survival Rate ; }, abstract = {Malignant pleural mesothelioma (MPM), a rare malignancy with a poor prognosis, is mainly caused by exposure to asbestos or other organic fibers, but the underlying genetic mechanism is not fully understood. Genetic alterations and causes for multiple primary cancer development including MPM are unknown. We used whole exome sequencing to identify somatic mutations in a patient with MPM and two additional primary cancers who had no evidence of venous, arterial, lymphovascular, or perineural invasion indicating dissemination of a primary lung cancer to the pleura. We found that the MPM had R282W, a key TP53 mutation, and genome-wide allelic loss or loss of heterozygosity, a distinct genomic alteration not previously described in MPM. We identified frequent inactivating SETDB1 mutations in this patient and in 68 additional MPM patients (mutation frequency: 10%, 7/69) by targeted deep sequencing. Our observations suggest the possibility of a new genetic mechanism in the development of either MPM or multiple primary cancers. The frequent SETDB1 inactivating mutations suggest there could be new diagnostic or therapeutic options for MPM.}, } @article {pmid26822314, year = {2016}, author = {}, title = {Comments on the causation of malignant mesothelioma: rebutting the false concept that recent exposures to asbestos do not contribute to causation of mesothelioma.}, journal = {Industrial health}, volume = {54}, number = {1}, pages = {92-93}, pmid = {26822314}, issn = {1880-8026}, mesh = {Asbestos/*adverse effects ; Humans ; Italy ; *Liability, Legal ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; Occupational Exposure/adverse effects/*legislation & jurisprudence ; Pleural Neoplasms/*etiology ; }, abstract = {The Collegium Ramazzini is an international scientific society that examines critical issues in occupational and environmental medicine with a view towards action to prevent disease and promote health. The Collegium derives its name from Bernardino Ramazzini, the father of occupational medicine, a professor of medicine of the Universities of Modena and Padua in the late 1600s and the early 1700s. The Collegium is comprised of 180 physicians and scientists from 35 countries, each of whom is elected to membership. The Collegium is independent of commercial interests.}, } @article {pmid26822313, year = {2016}, author = {}, title = {The global health dimensions of asbestos and asbestos-related diseases.}, journal = {Industrial health}, volume = {54}, number = {1}, pages = {87-91}, pmid = {26822313}, issn = {1880-8026}, mesh = {Asbestos/*adverse effects ; Asbestosis/epidemiology/etiology/*prevention & control ; *Developed Countries ; *Developing Countries ; *Global Health ; Humans ; International Cooperation ; Mesothelioma/*epidemiology/prevention & control ; }, abstract = {The Collegium Ramazzini is an international scientific society that examines critical issues in occupational and environmental medicine with a view towards action to prevent disease and promote health. The Collegium derives its name from Bernardino Ramazzini, the father of occupational medicine, a professor of medicine of the Universities of Modena and Padua in the late 1600s and the early 1700s. The Collegium is comprised of 180 physicians and scientists from 35 countries, each of whom is elected to membership. The Collegium is independent of commercial interests.}, } @article {pmid26822249, year = {2016}, author = {Bianchi, C and Bianchi, T}, title = {[Non-Hodgkin lymphoma and asbestos exposure].}, journal = {La Medicina del lavoro}, volume = {107}, number = {1}, pages = {73-74}, pmid = {26822249}, issn = {0025-7818}, mesh = {Aged ; Asbestos/*adverse effects ; *Carcinogens ; Female ; Humans ; Lymphoma, Non-Hodgkin/*etiology ; Male ; Mesothelioma/*etiology ; Orchiectomy ; Pleural Neoplasms/*etiology ; Testicular Neoplasms/etiology ; }, } @article {pmid26822244, year = {2016}, author = {Miscetti, G and Bodo, P and Lumare, A and Abbritti, EP and Garofani, P and Burani, V}, title = {[Asbestos exposure assessment in the first case of intrasplenic mesothelioma].}, journal = {La Medicina del lavoro}, volume = {107}, number = {1}, pages = {29-36}, pmid = {26822244}, issn = {0025-7818}, mesh = {Asbestos/*adverse effects ; Asbestos, Amosite/adverse effects ; Asbestos, Crocidolite/adverse effects ; Asbestos, Serpentine/adverse effects ; *Carcinogens ; *Food Packaging ; Humans ; Lung Neoplasms/diagnosis/*etiology ; Male ; *Medical History Taking ; Mesothelioma/diagnosis/*etiology ; Mesothelioma, Malignant ; Middle Aged ; Risk Assessment ; Splenic Neoplasms/diagnosis/*etiology ; }, abstract = {BACKGROUND: In 2013 the International Journal of Surgical Pathology published a case report of intrasplenic malignant mesothelioma (MM) in a 48-year-old man: it was the first report in literature describing a case of primitive intra-splenic MM, described without a history of asbestos exposure.

OBJECTIVE: To verify the possible past exposure to asbestos, ignored by the patient himself, by studying in depth his environmental and occupational history.

METHODS: Information about the occupational and non-occupational history of the subject was collected by Experts of the Operational Unit of Occupational Health and Safety Control (UOC PSAL) of the Local Health Unit Umbria 1 - Perugia, using the Italian National Mesothelioma Register (ReNaM) questionnaire and guide lines; an inspection was  carried out at the past canning industry where the patient worked in the period 1982-1990 and material was taken to be analysed by MOCF and SEM.

RESULTS: Samples showed the presence of asbestos  fibres belonging to the amphibole class (amosite and crocidolite) and to the serpentine class (chrysotile).

CONCLUSIONS: The survey described the past occupational exposure to asbestos in a canning industry, where  the subject worked in the period 1982-1990,  unknown to the patient himself. The authors strongly confirm the  usefulness of standardized methods, such as the ReNaM Questionnaire, and the importance of technical expertise of the investigator to find and analyse the suspect materials and to demonstrate  possible past occupational exposure to asbestos.}, } @article {pmid26822243, year = {2016}, author = {Mensi, C and Poltronieri, A and Romano, A and Dallari, B and Riboldi, L and Bertazzi, PA and Consonni, D}, title = {[Malignant mesotheliomas with unknown exposure to asbestos: a re-examination].}, journal = {La Medicina del lavoro}, volume = {107}, number = {1}, pages = {22-28}, pmid = {26822243}, issn = {0025-7818}, mesh = {Asbestos/*adverse effects ; *Carcinogens ; Clothing/*adverse effects ; Female ; Humans ; Incidence ; Italy/epidemiology ; Lung Neoplasms/diagnosis/epidemiology/*etiology ; Male ; Manufactured Materials/adverse effects ; Mesothelioma/diagnosis/epidemiology/*etiology ; Mesothelioma, Malignant ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/diagnosis/epidemiology/*etiology ; Retrospective Studies ; Risk Assessment ; }, abstract = {INTRODUCTION: Malignant Mesothelioma (MM) is a rare neoplasm associated with asbestos exposure. In 24,5% of MM cases reported to the Lombardy Mesothelioma Registry (LMR), asbestos exposure has been defined as "unknown".

OBJECTIVE: To evaluate the cases with "unknown exposure to asbestos" diagnosed in 2000-2004 in agreement with new knowledge about source of asbestos exposure.

METHODS: Information regarding exposure has been reviewed in order to select the cases susceptible of further investigations, including: interview of relatives and/or colleagues; further evaluations by local PSAL (Prevention and Security in workplace) services; contact of industrial hygienists; analysis of production processes. The same procedure has been followed for extra-occupational exposure. These cases have been subjected to the LMR evaluation group.

RESULTS: Fourthy four out of 364 (12,1%) MM have been reclassified. In 47,7% of the cases, a "possible occupational exposure" has been recognized, 15,9% have been attributed a "certain occupational exposure", while 36,4% an extra-occupational (domestic, environmental and leisure-time) exposure. No significant differences between age, sex, cancer site, diagnostic certainty, residence, year of diagnosis, interviewed subjects were detected. The occupational sector with the highest amount of reclassifications was the clothing production.

CONCLUSIONS: The detailed reconstruction of clinical and occupational history and of lifestyle habits of patients affected by MM, close cooperation with Local Services of Occupational Medicine and literature review make it possible for previously overlooked asbestos exposure to be acknowledged.}, } @article {pmid26822071, year = {2016}, author = {Scherpereel, A}, title = {[Asbestos and respiratory diseases].}, journal = {Presse medicale (Paris, France : 1983)}, volume = {45}, number = {1}, pages = {117-132}, doi = {10.1016/j.lpm.2015.12.011}, pmid = {26822071}, issn = {2213-0276}, mesh = {Asbestos/*adverse effects ; Asbestosis/etiology ; Fibrosis/etiology ; Humans ; Lung Neoplasms/chemically induced ; Mesothelioma/chemically induced ; Mesothelioma, Malignant ; Pleura/pathology ; Respiration Disorders/*chemically induced ; }, abstract = {Previous occupational asbestos exposure (more rarely environmental or domestic exposure) may induce various pleural and/or pulmonary, benign or malignant diseases, sometimes with a very long latency for malignant mesothelioma (MM). Asbestos has been widely extracted and used in Western countries and in emerging or developing countries, resulting in a peak of MM incidence in France around 2020 and likely in a world pandemic of asbestos-induced diseases. These patients have mostly benign respiratory diseases (pleural plugs) but may also be diagnosed with lung cancer or malignant pleural mesothelioma, and have a global poor outcome. New therapeutic tools (targeted therapies, immunotherapy…) with first promising results are developed. However, it is crucial to obtain a full ban of asbestos use worldwide, and to do a regular follow-up of asbestos-exposed subjects, mostly if they are already diagnosed with benign respiratory diseases. Finally, new cancers (larynx and ovary) were recently added to the list of asbestos-induced tumors.}, } @article {pmid26821095, year = {2016}, author = {van Zandwijk, N and Soeberg, M and Reid, G}, title = {Using a multidisciplinary approach to combat the burden of asbestos-related disease.}, journal = {The Medical journal of Australia}, volume = {204}, number = {2}, pages = {52}, doi = {10.5694/mja15.01209}, pmid = {26821095}, issn = {1326-5377}, mesh = {Age Distribution ; Asbestosis/*complications/diagnosis/epidemiology/*prevention & control ; Australia/epidemiology ; Evidence-Based Medicine ; Humans ; Incidence ; *Interdisciplinary Communication ; Mesothelioma/diagnosis/epidemiology/*etiology/*prevention & control ; Pleural Neoplasms/diagnosis/epidemiology/*etiology/*prevention & control ; Practice Guidelines as Topic ; Risk Factors ; Sex Distribution ; }, } @article {pmid26821092, year = {2016}, author = {Musk, AW and de Klerk, NH and Nowak, AK}, title = {Asbestos exposure: challenges for Australian clinicians.}, journal = {The Medical journal of Australia}, volume = {204}, number = {2}, pages = {48-49}, doi = {10.5694/mja15.01072}, pmid = {26821092}, issn = {1326-5377}, mesh = {Age Distribution ; Asbestos/*adverse effects ; Australia/epidemiology ; Environmental Exposure/*adverse effects ; Humans ; Lung Neoplasms/epidemiology/*etiology ; Mesothelioma/epidemiology/*etiology ; Risk Factors ; Sex Distribution ; }, } @article {pmid26820281, year = {2016}, author = {Markowitz, S}, title = {Erratum to: Asbestos-Related Lung Cancer and Malignant Mesothelioma of the Pleura: Selected Current Issues (Semin Respir Crit Care Med 2015;36(3):334-346).}, journal = {Seminars in respiratory and critical care medicine}, volume = {37}, number = {1}, pages = {143-144}, doi = {10.1055/s-0035-1570120}, pmid = {26820281}, issn = {1098-9048}, } @article {pmid26818092, year = {2016}, author = {Crovella, S and Bianco, AM and Vuch, J and Zupin, L and Moura, RR and Trevisan, E and Schneider, M and Brollo, A and Nicastro, EM and Cosenzi, A and Zabucchi, G and Borelli, V}, title = {Iron signature in asbestos-induced malignant pleural mesothelioma: A population-based autopsy study.}, journal = {Journal of toxicology and environmental health. Part A}, volume = {79}, number = {3}, pages = {129-141}, doi = {10.1080/15287394.2015.1123452}, pmid = {26818092}, issn = {1528-7394}, mesh = {Adult ; Aged ; Asbestos/*toxicity ; *Autopsy ; Case-Control Studies ; Female ; Ferritins/genetics ; Gene Frequency ; Genetic Markers ; Humans ; Iron/*metabolism ; Lung Neoplasms/chemically induced/genetics/*pathology ; Male ; Membrane Proteins/genetics ; Mesothelioma/chemically induced/genetics/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Mutation, Missense ; Oxidoreductases ; Polymorphism, Single Nucleotide ; Transferrin/genetics ; Young Adult ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive cancer with poor prognosis. The development of MPM is frequently linked to inhalation of asbestos fibers. A genetic component of susceptibility to this disease is suggested by the observation that some individuals develop MPM following lower doses of asbestos exposure, whereas others exposed to higher quantities do not seem to be affected. This hypothesis is supported also by frequent reports of MPM familial clustering. Despite the widely recognized role of iron (Fe) in cellular asbestos-induced pulmonary toxicity, the role of the related gene polymorphisms in the etiology of MPM has apparently not been evaluated. Eighty-six single-nucleotide polymorphisms (SNPs) of 10 Fe-metabolism genes were examined by exploiting formalin-fixed paraffin-embedded postmortem samples from 77 patients who died due to MPM (designated AEM) and compared with 48 who were exposed to asbestos but from died in old age of cause other than asbestos (designated AENM). All subjects showed objective signs of asbestos exposure. Three SNPs, localized in the ferritin heavy polypeptide, transferrin, and hephaestin genes, whose frequencies were distributed differently in AEM and AENM populations, were identified. For ferritin and transferrin the C/C and the G/G genotypes, respectively, representing intronic polymorphisms, were significantly associated with protection against MPM and need to be considered as possible genetic markers of protection. Similarly, the C/C hephaestin SNP, a missense variation of this multicopper ferroxidase encoding gene, may be related, also functionally, with protection against MPM. In conclusion, it is proposed that three Fe metabolism-associated genes, significantly associated with protection against development of MPM, may serve as protective markers for this aggressive tumor.}, } @article {pmid26811322, year = {2016}, author = {Kottek, M and Kilpatrick, DJ}, title = {Estimating Occupational Exposure to Asbestos in Australia.}, journal = {The Annals of occupational hygiene}, volume = {60}, number = {4}, pages = {531-532}, doi = {10.1093/annhyg/mew002}, pmid = {26811322}, issn = {1475-3162}, mesh = {*Asbestos ; Australia ; Humans ; Mesothelioma ; Occupational Diseases ; *Occupational Exposure ; }, } @article {pmid26807072, year = {2016}, author = {Morré, DJ and Hostetler, B and Taggart, DJ and Morré, DM and Musk, AW and Robinson, BW and Creaney, J}, title = {ENOX2-based early detection (ONCOblot) of asbestos-induced malignant mesothelioma 4-10 years in advance of clinical symptoms.}, journal = {Clinical proteomics}, volume = {13}, number = {}, pages = {2}, pmid = {26807072}, issn = {1542-6416}, abstract = {BACKGROUND: Malignant mesothelioma is an aggressive, almost uniformly fatal tumor, caused primarily by exposure to asbestos. In this study, serum presence of mesothelioma-specific protein transcript variants of ecto-nicotinamide adenine dinucleotide oxidase disulfide-thiol exchanger 2 (ENOX2), a recently identified marker of malignancy, were investigated using the ONCOblot tissue of origin cancer detection test.

METHODS: Sequential serum samples collected from asbestos-exposed individuals prior to the development of frank mesothelioma were assayed for ENOX2 presence by 2-D gel immunoblot analysis to determine how long in advance of clinical symptoms mesothelioma-specific ENOX2 transcript variants could be detected.

RESULTS: Two mesothelioma-specific ENOX2 protein transcript variants were detected in the serum of asbestos-exposed individuals 4-10 years prior to clinical diagnosis of malignant mesothelioma (average 6.2 years). Either one or both ENOX2 protein transcript variants indicative of malignant mesothelioma were absent in 14 of 15 subjects diagnosed with benign pleural plaques either with or without accompanying asbestosis.

CONCLUSIONS: In a population of asbestos-exposed subjects who eventually developed malignant mesothelioma, ENOX2 protein transcript variants characteristic of malignant mesothelioma were present in serum 4-10 years in advance of clinical symptoms. As with all biomarker studies, these observations require validation in a larger, independent cohort of patients and should include prospective as well as retrospective sampling.}, } @article {pmid26800709, year = {2016}, author = {Soeberg, MJ and Leigh, J and Driscoll, T and Armstrong, B and Young, JM and van Zandwijk, N}, title = {Incidence and survival trends for malignant pleural and peritoneal mesothelioma, Australia, 1982-2009.}, journal = {Occupational and environmental medicine}, volume = {73}, number = {3}, pages = {187-194}, doi = {10.1136/oemed-2015-103309}, pmid = {26800709}, issn = {1470-7926}, mesh = {Adolescent ; Adult ; Aged ; Asbestos/*adverse effects ; Australia/epidemiology ; *Carcinogens ; Case-Control Studies ; Child ; Child, Preschool ; *Environmental Exposure ; Female ; Humans ; Incidence ; Infant ; Infant, Newborn ; Lung/pathology ; Lung Neoplasms/*epidemiology/mortality ; Male ; Mesothelioma/*epidemiology/mortality ; Mesothelioma, Malignant ; Middle Aged ; Peritoneal Neoplasms/*epidemiology/mortality ; Peritoneum/pathology ; Pleural Neoplasms/*epidemiology/mortality ; Young Adult ; }, abstract = {BACKGROUND: Australia is known to have had one of the highest per-capita asbestos consumption rates, yet there are few contemporary reports on malignant mesothelioma trends.

METHODS: Data on 10 930 people with malignant pleural mesothelioma (MPM) and 640 people with malignant peritoneal mesothelioma diagnosed in Australia during 1982-2009 were analysed. Observed incidence rate trends were quantified. Incidence rates were projected up to 2030 using observed incident cases during 1982-2012. The relative per-decade change in excess mortality during 1999-2009 was estimated.

RESULTS: During 1982-2009, acceleration in MPM age-standardised incidence rates were highest for women and those aged 75 years and above, with average annual percentage changes of +4.9 (95% CI 3.6 to 6.2) and +7.2 (95% CI 5.4 to 9.0), respectively. Age-standardised incidence rates for men with MPM aged 0-64 years decelerated rapidly during 2003-2009, an average annual percentage change of -5.1% (95% CI -7.6% to -2.5%). Overall, male age-specific MPM incidence rates in the age group of 65-74 year during 2010-2030 are projected to decline with rates projected to increase for older men and women with MPM. There was a statistically significant 16% relative reduction in the excess mortality rate (EMR) up to 5 years postdiagnosis for people diagnosed with malignant pleural and peritoneal mesothelioma combined in 2009 compared with those diagnosed in 1999, an EMR ratio of 0.84 (95% CI 0.77 to 0.92).

CONCLUSIONS: Australia's malignant mesothelioma incidence rates appear to have reached maximum levels but with differences over time by age, gender and tumour location. Improvements over time in survival provide a glimpse of hope for this almost invariably fatal disease.}, } @article {pmid26788989, year = {2016}, author = {Cortez, BA and Rezende-Teixeira, P and Redick, S and Doxsey, S and Machado-Santelli, GM}, title = {Multipolar mitosis and aneuploidy after chrysotile treatment: a consequence of abscission failure and cytokinesis regression.}, journal = {Oncotarget}, volume = {7}, number = {8}, pages = {8979-8992}, pmid = {26788989}, issn = {1949-2553}, mesh = {*Aneuploidy ; Asbestos, Serpentine/*pharmacology ; Aurora Kinase B/metabolism ; Calcium-Binding Proteins/metabolism ; Cell Cycle Proteins/metabolism ; Cell Line, Tumor ; Endosomal Sorting Complexes Required for Transport/metabolism ; Humans ; Lung Neoplasms/chemically induced/*pathology ; Microfilament Proteins/metabolism ; Mitosis/*drug effects ; Septins/metabolism ; }, abstract = {Chrysotile, like other types of asbestos, has been associated with mesothelioma, lung cancer and asbestosis. However, the cellular abnormalities induced by these fibers involved in cancer development have not been elucidated yet. Previous works show that chrysotile fibers induce features of cancer cells, such as aneuploidy, multinucleation and multipolar mitosis. In the present study, normal and cancer derived human cell lines were treated with chrysotile and the cellular and molecular mechanisms related to generation of aneuploid cells was elucidated. The first alteration observed was cytokinesis regression, the main cause of multinucleated cells formation and centrosome amplification. The multinucleated cells formed after cytokinesis regression were able to progress through cell cycle and generated aneuploid cells after abnormal mitosis. To understand the process of cytokinesis regression, localization of cytokinetic proteins was investigated. It was observed mislocalization of Anillin, Aurora B, Septin 9 and Alix in the intercellular bridge, and no determination of secondary constriction and abscission sites. Fiber treatment also led to overexpression of genes related to cancer, cytokinesis and cell cycle. The results show that chrysotile fibers induce cellular and molecular alterations in normal and tumor cells that have been related to cancer initiation and progression, and that tetraploidization and aneuploid cell formation are striking events after fiber internalization, which could generate a favorable context to cancer development.}, } @article {pmid26780987, year = {2016}, author = {Cregan, S and McDonagh, L and Gao, Y and Barr, MP and O'Byrne, KJ and Finn, SP and Cuffe, S and Gray, SG}, title = {KAT5 (Tip60) is a potential therapeutic target in malignant pleural mesothelioma.}, journal = {International journal of oncology}, volume = {48}, number = {3}, pages = {1290-1296}, doi = {10.3892/ijo.2016.3335}, pmid = {26780987}, issn = {1791-2423}, mesh = {Apoptosis ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Separation ; Chemokines/metabolism ; Cytokines/metabolism ; Epithelium/metabolism ; *Gene Expression Regulation, Neoplastic ; Histone Acetyltransferases/*metabolism ; Humans ; Inflammation ; Lung Neoplasms/*metabolism ; Lysine Acetyltransferase 5 ; Mesothelioma/*metabolism ; Mesothelioma, Malignant ; Pleural Neoplasms/*metabolism ; Risk Factors ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare aggressive cancer of the pleura. Asbestos exposure (through inhalation) is the most well established risk factor for mesothelioma. The current standard of care for patients suffering from MPM is a combination of cisplatin and pemetrexed (or alternatively cisplatin and raltitrexed). Most patients, however, die within 24 months of diagnosis. New therapies are therefore urgently required for this disease. Lysine acetyltransferases (KATs) including KAT5 have been linked with the development of cisplatin resistance. This gene may therefore be altered in MPM and could represent a novel candidate target for intervention. Using RT-PCR screening the expression of all known KAT5 variants was found to be markedly increased in malignant tumors compared to benign pleura. When separated according to histological subtype, KAT5 was significantly overexpressed in both the sarcomatoid and biphasic subgroups for all transcript variants. A panel of MPM cell lines including the normal pleural cells LP9 and Met5A was screened for expression of KAT5 variants. Treatment of cells with a small molecule inhibitor of KAT5 (MG-149) caused significant inhibition of cellular proliferation (p<0.0001), induction of apoptosis and was accompanied by significant induction of pro-inflammatory cytokines/chemokines.}, } @article {pmid26776867, year = {2016}, author = {Brims, FJ and Meniawy, TM and Duffus, I and de Fonseka, D and Segal, A and Creaney, J and Maskell, N and Lake, RA and de Klerk, N and Nowak, AK}, title = {A Novel Clinical Prediction Model for Prognosis in Malignant Pleural Mesothelioma Using Decision Tree Analysis.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {11}, number = {4}, pages = {573-582}, doi = {10.1016/j.jtho.2015.12.108}, pmid = {26776867}, issn = {1556-1380}, mesh = {Aged ; Cohort Studies ; *Decision Trees ; Female ; Humans ; Lung Neoplasms/*diagnosis/mortality/pathology ; Male ; Mesothelioma/*diagnosis/mortality/pathology ; Mesothelioma, Malignant ; Models, Statistical ; Pleural Neoplasms/*diagnosis/mortality/pathology ; Prognosis ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is a rare cancer with a heterogeneous prognosis. Prognostic models are not widely utilized clinically. Classification and regression tree (CART) analysis examines the interaction of multiple variables with a given outcome.

METHODS: Between 2005 and 2014, all cases with pathologically confirmed MPM had routinely available histological, clinical, and laboratory characteristics recorded. Classification and regression tree analysis was performed using 29 variables with 18-month survival as the dependent variable. Risk groups were refined according to survival and clinical characteristics. The model was then tested on an external international cohort.

RESULTS: A total of 482 cases were included in the derivation cohort; the median survival was 12.6 months, and the median age was 69 years. The model defined four risk groups with clear survival differences (p < 0.0001). The strongest predictive variable was the presence of weight loss. The group with the best survival at 18 months (86.7% alive, median survival 34.0 months, termed risk group 1) had no weight loss, a hemoglobin level greater than 153 g/L, and a serum albumin level greater than 43 g/L. The group with the worst survival (0% alive, median survival 7.5 months, termed risk group 4d) had weight loss, a performance score of 0 or 1, and sarcomatoid histological characteristics. The C-statistic for the model was 0.761, and the sensitivity was 94.5%. Validation on 174 external cases confirmed the model's ability to discriminate between risk groups in an alternative data set with fair performance (C-statistic 0.68).

CONCLUSIONS: We have developed and validated a simple, clinically relevant model to reliably discriminate patients at high and lower risk of death using routinely available variables from the time of diagnosis in unselected populations of patients with MPM.}, } @article {pmid26773348, year = {2016}, author = {Tan, WK and Tan, MY and Tan, HM and Pathmanathan, R and Tan, WP}, title = {Well-differentiated Papillary Mesothelioma of the Tunica Vaginalis.}, journal = {Urology}, volume = {90}, number = {}, pages = {e7-8}, doi = {10.1016/j.urology.2015.12.046}, pmid = {26773348}, issn = {1527-9995}, mesh = {Adult ; Humans ; Male ; Mesothelioma/*pathology ; Testicular Neoplasms/*pathology ; }, abstract = {A 39-year-old man presented with painless scrotal swelling for 2 months. He denied any asbestos exposure but worked with wall and ceiling plaster. Physical exam revealed a large right scrotum which transilluminated. Scrotal ultrasonography revealed a large right hydrocele and a polypoidal mass along the anterior wall of the scrotum. Magnetic resonance imaging of the abdomen and computed tomography of the chest showed no metastases. He underwent a right inguinal scrotal exploration and wide excision of tunica vaginalis and a partial epididymectomy. Pathology revealed well-differentiated papillary mesothelioma of the tunica vaginalis. The patient had an uneventful recovery.}, } @article {pmid29900099, year = {2016}, author = {Giusti, L and Ciregia, F and Bonotti, A and Da Valle, Y and Donadio, E and Boldrini, C and Foddis, R and Giannaccini, G and Mazzoni, MR and Canessa, PA and Cristaudo, A and Lucacchini, A}, title = {Comparative proteomic analysis of malignant pleural mesothelioma: Focusing on the biphasic subtype.}, journal = {EuPA open proteomics}, volume = {10}, number = {}, pages = {42-49}, pmid = {29900099}, issn = {2212-9685}, abstract = {Malignant pleural mesothelioma (MPM) is a rare cancer originated from pleural mesothelial cells. MPM has been associated with long-term exposure to asbestos. In this work we performed a comparative proteomic analysis of biphasic pleural mesothelioma (B-PM). Tissue biopsies were obtained from 61 patients who were subjected to a diagnostic thoracoscopy. 2D/MS based approach was used for proteomic analysis. The 22 proteins found differentially expressed in B-PM, with respect to benign, were analyzed by Ingenuity Pathways Analysis and compared with those obtained for epitheliod pleural mesothelioma (E-PM). A different activation of transcription factors, proteins and cytokines were observed between two subtypes.}, } @article {pmid26770440, year = {2015}, author = {Yao, W and Yang, H and Huang, G and Yan, Y and Wang, H and Sun, D}, title = {Massive localized malignant pleural mesothelioma (LMPM): manifestations on computed tomography in 6 cases.}, journal = {International journal of clinical and experimental medicine}, volume = {8}, number = {10}, pages = {18367-18374}, pmid = {26770440}, issn = {1940-5901}, abstract = {OBJECTIVE: Our study analyzed the clinical symptoms and computed tomography (CT) manifestations of massive localized malignant pleural mesothelioma (LMPM) patients to improve the knowledge and diagnosis of this disease.

METHODS: Our study collected 6 massive LMPM patients pathologically confirmed by CT in the department of Radiology of the People's Hospital of Yuyao, Zhejiang Province, from January, 2007 to June, 2013; data of patients were also collected. The clinical symptoms, clinicopathological characteristics, CT manifestations, treatments and prognosis of enrolled patients were analyzed.

RESULTS: Our study enrolled 6 LMPM patients (2 males; 4 females) classified to epitheliated type (n = 4) and sarcomatous type (n = 2) with mean age of 62.7 ± 7.4, and 5 of them had a history of asbestos exposure. CT manifestations revealed that large soft-tissue mass close to pleura, which was smooth and lobulated, was discovered in all patients with maximum diameter of 10~15 cm and mean diameter of 13.67 ± 1.15 cm; The mean value of CT was 36.29 ± 2.62 HU; after enhancement, the mean value was increased to 76.36 ± 7.73 HU; patients showed zones of small patchy necrosis and large patchy necrosis. The following presentations were founded: enlargement of tumor vessel which showed arborization (2 patients), mass wrap around the descending aorta in left lower chest (1 patient), strips of fat density in mediastinum superior (1 patient), pleural tail sign (3 patients). Among 6 patients, pleural effusion (n = 4), mediastinal lymph node enlargement (n = 3), invasion and destruction of local ribs (n = 2). Median survival time of patients were 20 months (2 cases conducted operation), 24 (2 cases chose combined radiotherapy and chemotherapy) and less than 6 months (2 cases underwent chemotherapy).

CONCLUSION: To sum up, CT showed important diagnostic values on massive LMPM patients; patients with a history of asbestos exposure, large soft-tissue mass of pleura with an abundant blood supply and wrap around large vessels might increase the risk of massive LMPM.}, } @article {pmid26744692, year = {2015}, author = {Hara, N and Fujimoto, N and Miyamoto, Y and Yamagishi, T and Asano, M and Fuchimoto, Y and Wada, S and Ozaki, S and Kishimoto, T}, title = {Lymphoproliferative disorder in pleural effusion in a subject with past asbestos exposure.}, journal = {Respiratory medicine case reports}, volume = {16}, number = {}, pages = {169-171}, pmid = {26744692}, issn = {2213-0071}, abstract = {Primary effusion lymphoma (PEL) is a subtype of non-Hodgkin lymphoma that presents as serous effusions without detectable masses or organomegaly. Here we report a case of PEL-like lymphoma in a patient with past asbestos exposure. A 65-year-old man was referred to our hospital due to dyspnea upon exertion. He had been exposed to asbestos for three years in the construction industry. Chest X-ray and CT images demonstrated left pleural effusion. Cytological analysis of the pleural effusion revealed large atypical lymphocytes with distinct nuclear bodies and high nucleus-to-cytoplasm ratio. Immunohistochemical analyses showed that the cells were CD20(+), CD3(-), CD5(-), and CD10(-). These findings led to a diagnosis of diffuse large B-cell lymphoma. PEL or PEL-like lymphoma should be considered a potential cause of pleural effusion in subjects with past asbestos exposure.}, } @article {pmid26744667, year = {2015}, author = {Nakasuka, T and Fujimoto, N and Hara, N and Miyamoto, Y and Yamagishi, T and Asano, M and Nishi, H and Kishimoto, T}, title = {Foreign body granuloma mimicking recurrence of malignant pleural mesothelioma.}, journal = {Respiratory medicine case reports}, volume = {16}, number = {}, pages = {95-96}, pmid = {26744667}, issn = {2213-0071}, abstract = {A 72-year-old man visited our hospital due to right pleural effusion. He had worked as a welder at a shipbuilding company and had been exposed to asbestos. Cytological examination and thoracoscopic pleural biopsy yielded a diagnosis of epithelial malignant pleural mesothelioma (MPM); extrapleural pneumonectomy (EPP) was performed. Two years later, he became aware of right-back swelling that became a fist-sized mass over 2 months. Microscopy of a tissue specimen revealed no malignant cells, but did indicate foreign body granuloma. Subcutaneous lesions that develop after EPP do not necessarily result from the recurrence of MPM, but could have benign etiologies.}, } @article {pmid26743791, year = {2015}, author = {Gordon, R and Fitzgerald, S and Millette, J}, title = {Asbestos in commercial cosmetic talcum powder as a cause of mesothelioma in women.}, journal = {International journal of occupational and environmental health}, volume = {21}, number = {4}, pages = {347-348}, doi = {10.1080/10773525.2015.1122368}, pmid = {26743791}, issn = {2049-3967}, } @article {pmid26743790, year = {2015}, author = {Gordon, RE}, title = {Response to RE: Gordon R, Fitzgerald S, and Millette J. Asbestos in commercial cosmetic talcum powder as a cause of mesothelioma in women. Int J Occup Environ Health. 2014;20(4):318-332.}, journal = {International journal of occupational and environmental health}, volume = {21}, number = {4}, pages = {342-346}, pmid = {26743790}, issn = {2049-3967}, mesh = {Asbestos/*toxicity ; Cosmetics/*toxicity ; Female ; Humans ; Mesothelioma/*chemically induced ; Talc/*toxicity ; }, } @article {pmid26743789, year = {2015}, author = {Lee, R and Van Orden, D}, title = {Asbestos in commercial cosmetic talcum powder as a cause of mesothelioma in women.}, journal = {International journal of occupational and environmental health}, volume = {21}, number = {4}, pages = {337-341}, pmid = {26743789}, issn = {2049-3967}, mesh = {Asbestos/*toxicity ; Cosmetics/*toxicity ; Female ; Humans ; Mesothelioma/*chemically induced ; Talc/*toxicity ; }, } @article {pmid26733616, year = {2016}, author = {Napolitano, A and Antoine, DJ and Pellegrini, L and Baumann, F and Pagano, I and Pastorino, S and Goparaju, CM and Prokrym, K and Canino, C and Pass, HI and Carbone, M and Yang, H}, title = {HMGB1 and Its Hyperacetylated Isoform are Sensitive and Specific Serum Biomarkers to Detect Asbestos Exposure and to Identify Mesothelioma Patients.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {22}, number = {12}, pages = {3087-3096}, pmid = {26733616}, issn = {1557-3265}, support = {R01 CA198138/CA/NCI NIH HHS/United States ; G0700654/MRC_/Medical Research Council/United Kingdom ; MR/L006758/1/MRC_/Medical Research Council/United Kingdom ; U01 CA111295/CA/NCI NIH HHS/United States ; //Wellcome Trust/United Kingdom ; P30 CA071789/CA/NCI NIH HHS/United States ; U54 MD007584/MD/NIMHD NIH HHS/United States ; R01 CA160715/CA/NCI NIH HHS/United States ; }, mesh = {Acetylation ; Adult ; Aged ; Asbestos/*blood/toxicity ; Biomarkers/*blood ; *Environmental Exposure ; Extracellular Matrix Proteins/blood ; Female ; GPI-Linked Proteins/blood ; HMGB1 Protein/*blood/metabolism ; Humans ; Lung Neoplasms/blood/*diagnosis ; Male ; Mesothelin ; Mesothelioma/blood/*diagnosis ; Mesothelioma, Malignant ; Middle Aged ; Osteopontin/blood ; Pleural Effusion/blood/diagnosis ; Pleural Neoplasms/blood/*diagnosis ; Sensitivity and Specificity ; Young Adult ; }, abstract = {PURPOSE: To determine whether serum levels of high mobility group box protein 1 (HMGB1) could differentiate malignant mesothelioma patients, asbestos-exposed individuals, and unexposed controls.

EXPERIMENTAL DESIGN: Hyperacetylated and nonacetylated HMGB1 (together referred to as total HMGB1) were blindly measured in blood collected from malignant mesothelioma patients (n = 22), individuals with verified chronic asbestos exposure (n = 20), patients with benign pleural effusions (n = 13) or malignant pleural effusions not due to malignant mesothelioma (n = 25), and healthy controls (n = 20). Blood levels of previously proposed malignant mesothelioma biomarkers fibulin-3, mesothelin, and osteopontin were also measured in nonhealthy individuals.

RESULTS: HMGB1 serum levels reliably distinguished malignant mesothelioma patients, asbestos-exposed individuals, and unexposed controls. Total HMGB1 was significantly higher in malignant mesothelioma patients and asbestos-exposed individuals compared with healthy controls. Hyperacetylated HMGB1 was significantly higher in malignant mesothelioma patients compared with asbestos-exposed individuals and healthy controls, and did not vary with tumor stage. At the cut-off value of 2.00 ng/mL, the sensitivity and specificity of serum hyperacetylated HMGB1 in differentiating malignant mesothelioma patients from asbestos-exposed individuals and healthy controls was 100%, outperforming other previously proposed biomarkers. Combining HMGB1 and fibulin-3 provided increased sensitivity and specificity in differentiating malignant mesothelioma patients from patients with cytologically benign or malignant non-mesothelioma pleural effusion.

CONCLUSIONS: Our results are significant and clinically relevant as they provide the first biomarker of asbestos exposure and indicate that hyperacetylated HMGB1 is an accurate biomarker to differentiate malignant mesothelioma patients from individuals occupationally exposed to asbestos and unexposed controls. A trial to independently validate these findings will start soon. Clin Cancer Res; 22(12); 3087-96. ©2016 AACR.}, } @article {pmid26730866, year = {2016}, author = {Corcoran, JP and Psallidas, I and Ross, CL and Hallifax, RJ and Rahman, NM}, title = {Always Worth Another Look? Thoracic Ultrasonography before, during, and after Pleural Intervention.}, journal = {Annals of the American Thoracic Society}, volume = {13}, number = {1}, pages = {118-121}, doi = {10.1513/AnnalsATS.201508-559CC}, pmid = {26730866}, issn = {2325-6621}, support = {MR/L017091/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Aged ; Asbestos/adverse effects ; *Blood Loss, Surgical ; Humans ; Image-Guided Biopsy/adverse effects/methods ; Male ; *Mesothelioma/complications/etiology/pathology ; Occupational Exposure/adverse effects ; Perioperative Care/*methods ; Pleural Effusion/*diagnosis/etiology ; *Pleural Neoplasms/complications/etiology/pathology ; Thoracoscopy/adverse effects/methods ; Thorax/*diagnostic imaging ; Treatment Outcome ; Ultrasonography ; }, } @article {pmid26729015, year = {2016}, author = {Kawai, T and Tominaga, S and Hiroi, S and Ogata, S and Nakanishi, K and Kawahara, K and Sonobe, H and Hiroshima, K}, title = {Peritoneal malignant mesothelioma (PMM), and primary peritoneal serous carcinoma (PPSC) and reactive mesothelial hyperplasia (RMH) of the peritoneum. Immunohistochemical and fluorescence in situ hybridisation (FISH) analyses.}, journal = {Journal of clinical pathology}, volume = {69}, number = {8}, pages = {706-712}, doi = {10.1136/jclinpath-2015-203211}, pmid = {26729015}, issn = {1472-4146}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers/metabolism ; Cystadenocarcinoma, Serous/*diagnosis/genetics/metabolism ; Diagnosis, Differential ; Female ; Humans ; Hyperplasia/diagnosis/genetics/metabolism ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Lung Neoplasms/*diagnosis/genetics/metabolism ; Male ; Mesothelioma/*diagnosis/genetics/metabolism ; Mesothelioma, Malignant ; Middle Aged ; Peritoneal Neoplasms/diagnosis/genetics/metabolism ; Peritoneum/metabolism/*pathology ; Young Adult ; }, abstract = {AIMS: Peritoneal malignant mesothelioma (PMM) is an uncommon tumour, accounting for only 7-9% of all mesotheliomas in Japan. Differential diagnosis between PMM and primary peritoneal serous carcinoma (PPSC), a high-grade serous carcinoma, may be difficult, and separating reactive mesothelial hyperplasia (RMH) from PMM can be even more challenging.

METHODS: To help differentiate PMM from PPSC and RMH, we used immunohistochemistry to examine mesothelial-associated markers (calretinin, AE1/AE3, CK5/6, CAM5.2, D2-40, WT-1, HBME1, thrombomodulin), adenocarcinoma-associated markers (CEA, BerEP4, MOC31, ER (estrogen receptor), PgR, TTF-1, Claudin-4, Pax8), and malignant-related and benign-related markers (epithelial membrane antigen (EMA), desmin, GLUT-1, CD146 and IMP3), and FISH to examine for homozygous deletion of 9p21. We used formalin-fixed, paraffin-embedded blocks from 22 PMMs (M:F=18:4; subtypes: 16 epithelioid, 6 biphasic), 11 PPSCs and 23 RMHs.

RESULTS: Seventeen of the mesotheliomas (four PMM from women) were classified as diffuse, while five were localised. Calretinin was 91% positive in PMM, but negative in PPSC (specificity, 100%). BerEP4, Claudin-4 and PAX8 were all 100% positive in PPSC (specificities, 100%, 95% and 95%, respectively, for excluding PMM). For distinguishing PMM and RMH, sensitivity for EMA in mesothelioma was 68%, while for IMP3 and GLUT-1 it was 64% and 50%, respectively, all with high specificities. FISH analysis revealed homozygous deletion of the 9p21 locus in 11/13 PMMs, but in 0/11 RMHs.

CONCLUSIONS: Calretinin and BerEP4 may be the best positive markers for differentiating PMM from PPSC. EMA, in combination with IMP3 and desmin, is useful, and homozygous deletion of 9p21 may be helpful, for differentiating PMM from RMH.}, } @article {pmid26725926, year = {2016}, author = {Egilman, D and Bird, T}, title = {Short fiber tremolite free chrysotile mesothelioma cohort revealed.}, journal = {American journal of industrial medicine}, volume = {59}, number = {3}, pages = {196-199}, doi = {10.1002/ajim.22552}, pmid = {26725926}, issn = {1097-0274}, mesh = {*Asbestos, Serpentine ; Cohort Studies ; Humans ; *Mesothelioma ; New Jersey ; *Occupational Exposure ; *Plastics ; *Respiratory Tract Neoplasms ; }, abstract = {In 1995, Dell and Teta published a cohort mortality study of asbestos molding compound workers at a Union Carbide Corporation (UCC) plastics manufacturing plant in Bound Brook, New Jersey. They reported that the factory workers were exposed to "asbestos (mostly chrysotile)," implying that the asbestos used at the Bound Brook plant occasionally contained amphiboles. However, UCC statements and testimony from recent litigation indicate that the Bound Brook plant exclusively used short fiber chrysotile asbestos. These recent documents also point to lower exposures than those reported by Dell and Teta. This chrysotile-only cohort should be included in analyses of chrysotile potency.}, } @article {pmid26722325, year = {2015}, author = {Furukawa, M and Toyooka, S and Hayashi, T and Yamamoto, H and Fujimoto, N and Soh, J and Hashida, S and Shien, K and Asano, H and Aoe, K and Okabe, K and Pass, HI and Tsukuda, K and Kishimoto, T and Miyoshi, S}, title = {DNA copy number gains in malignant pleural mesothelioma.}, journal = {Oncology letters}, volume = {10}, number = {5}, pages = {3274-3278}, pmid = {26722325}, issn = {1792-1074}, abstract = {Malignant pleural mesothelioma (MPM) is a highly aggressive tumor with an extremely poor prognosis. The incidence of MPM is increasing as a result of widespread exposure to asbestos. The molecular pathogenesis of MPM remains unclear. The present study analyzed the frequency of various genomic copy number gains (CNGs) in MPM using reverse transcription-quantitative polymerase chain reaction. A total of 83 primary MPMs and 53 primary lung adenocarcinomas were analyzed to compare the CNGs of EGFR, KRAS, MET, FGFR1 and SOX2. In MPM, the CNGs of EGFR, KRAS, MET, FGFR1 and SOX2 were detected in 12 (14.5%), 8 (9.6%), 5 (6.0%), 4 (4.8%) and 1 (1.2%) of the samples, respectively. In lung adenocarcinomas, the CNGs of EGFR, KRAS, MET, FGFR1 and SOX2 were detected in 21 (39.6%), 12 (22.6%), 5 (9.4%), 10 (18.9%) and 0 (0.0%) of the samples, respectively. The CNGs of EGFR, KRAS and FGFR1 were significantly less frequent in the MPMs compared with the lung adenocarcinomas (P=0.0018, 0.048 and 0.018, respectively). Overall, the MPMs exhibited these CNGs less frequently compared with the lung adenocarcinomas (P=0.0002). The differences in CNGs between the two tumor types suggested that they are genetically different.}, } @article {pmid26719535, year = {2016}, author = {Ohar, JA and Cheung, M and Talarchek, J and Howard, SE and Howard, TD and Hesdorffer, M and Peng, H and Rauscher, FJ and Testa, JR}, title = {Germline BAP1 Mutational Landscape of Asbestos-Exposed Malignant Mesothelioma Patients with Family History of Cancer.}, journal = {Cancer research}, volume = {76}, number = {2}, pages = {206-215}, pmid = {26719535}, issn = {1538-7445}, support = {P30 CA010815/CA/NCI NIH HHS/United States ; R01 CA175691/CA/NCI NIH HHS/United States ; R01 CA148805/CA/NCI NIH HHS/United States ; CA175691/CA/NCI NIH HHS/United States ; P30 ES013508/ES/NIEHS NIH HHS/United States ; P42 ES023720/ES/NIEHS NIH HHS/United States ; P30 CA006927/CA/NCI NIH HHS/United States ; CA-06927/CA/NCI NIH HHS/United States ; }, mesh = {Asbestos/*adverse effects ; Cohort Studies ; Female ; Genetic Predisposition to Disease ; *Germ-Line Mutation ; HEK293 Cells ; Humans ; Lung Neoplasms/etiology/*genetics ; Male ; Mesothelioma/etiology/*genetics ; Mesothelioma, Malignant ; Middle Aged ; Mutation, Missense ; Tumor Suppressor Proteins/*genetics/metabolism ; Ubiquitin Thiolesterase/*genetics/metabolism ; }, abstract = {Heritable mutations in the BAP1 tumor suppressor gene predispose individuals to mesothelioma and other cancers. However, a large-scale assessment of germline BAP1 mutation incidence and associated clinical features in mesothelioma patients with a family history of cancer has not been reported. Therefore, we examined the germline BAP1 mutation status of 150 mesothelioma patients with a family history of cancer, 50 asbestos-exposed control individuals with a family history of cancers other than mesothelioma, and 153 asbestos-exposed individuals without familial cancer. No BAP1 alterations were found in control cohorts, but were identified in nine of 150 mesothelioma cases (6%) with a family history of cancer. Alterations among these cases were characterized by both missense and frameshift mutations, and enzymatic activity of BAP1 missense mutants was decreased compared with wild-type BAP1. Furthermore, BAP1 mutation carriers developed mesothelioma at an earlier age that was more often peritoneal than pleural (five of nine) and exhibited improved long-term survival compared to mesothelioma patients without BAP1 mutations. Moreover, many tumors harboring BAP1 germline mutations were associated with BAP1 syndrome, including mesothelioma and ocular/cutaneous melanomas, as well as renal, breast, lung, gastric, and basal cell carcinomas. Collectively, these findings suggest that mesothelioma patients presenting with a family history of cancer should be considered for BAP1 genetic testing to identify those individuals who might benefit from further screening and routine monitoring for the purpose of early detection and intervention.}, } @article {pmid26719230, year = {2016}, author = {Zalcman, G and Mazieres, J and Margery, J and Greillier, L and Audigier-Valette, C and Moro-Sibilot, D and Molinier, O and Corre, R and Monnet, I and Gounant, V and Rivière, F and Janicot, H and Gervais, R and Locher, C and Milleron, B and Tran, Q and Lebitasy, MP and Morin, F and Creveuil, C and Parienti, JJ and Scherpereel, A and , }, title = {Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): a randomised, controlled, open-label, phase 3 trial.}, journal = {Lancet (London, England)}, volume = {387}, number = {10026}, pages = {1405-1414}, doi = {10.1016/S0140-6736(15)01238-6}, pmid = {26719230}, issn = {1474-547X}, mesh = {Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Bevacizumab/*administration & dosage/adverse effects ; Cisplatin/*administration & dosage/adverse effects ; Creatinine/blood ; Female ; Humans ; Hypertension/epidemiology ; Lung Neoplasms/*drug therapy/mortality/pathology ; Male ; Mesothelioma/*drug therapy/mortality/pathology ; Mesothelioma, Malignant ; Middle Aged ; Pemetrexed/*administration & dosage/adverse effects ; Pleural Neoplasms/*drug therapy/mortality/pathology ; Proteinuria/epidemiology ; Thrombosis/epidemiology ; Vascular Endothelial Growth Factor A/blood ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma is an aggressive cancer with poor prognosis, linked to occupational asbestos exposure. Vascular endothelial growth factor is a key mitogen for malignant pleural mesothelioma cells, therefore targeting of vascular endothelial growth factor might prove effective. We aimed to assess the effect on survival of bevacizumab when added to the present standard of care, cisplatin plus pemetrexed, as first-line treatment of advanced malignant pleural mesothelioma.

METHODS: In this randomised, controlled, open-label, phase 3 trial, we recruited patients aged 18-75 years with unresectable malignant pleural mesothelioma who had not received previous chemotherapy, had an Eastern Cooperative Oncology Group performance status of 0-2, had no substantial cardiovascular comorbidity, were not amenable to curative surgery, had at least one evaluable (pleural effusion) or measurable (pleural tumour solid thickening) lesion with CT, and a life expectancy of >12 weeks from 73 hospitals in France. Exclusion criteria were presence of central nervous system metastases, use of antiaggregant treatments (aspirin ≥325 mg per day, clopidogrel, ticlopidine, or dipyridamole), anti-vitamin K drugs at a curative dose, treatment with low-molecular-weight heparin at a curative dose, and treatment with non-steroidal anti-inflammatory drugs. We randomly allocated patients (1:1; minimisation method used [random factor of 0·8]; patients stratified by histology [epithelioid vs sarcomatoid or mixed histology subtypes], performance status score [0-1 vs 2], study centre, or smoking status [never smokers vs smokers]) to receive intravenously 500 mg/m(2) pemetrexed plus 75 mg/m(2) cisplatin with (PCB) or without (PC) 15 mg/kg bevacizumab in 21 day cycles for up to six cycles, until progression or toxic effects. The primary outcome was overall survival (OS) in the intention-to treat population. Treatment was open label. This IFCT-GFPC-0701 trial is registered with ClinicalTrials.gov, number NCT00651456.

FINDINGS: From Feb 13, 2008, to Jan 5, 2014, we randomly assigned 448 patients to treatment (223 [50%] to PCB and 225 [50%] to PC). OS was significantly longer with PCB (median 18·8 months [95% CI 15·9-22·6]) than with PC (16·1 months [14·0-17·9]; hazard ratio 0·77 [0·62-0·95]; p=0·0167). Overall, 158 (71%) of 222 patients given PCB and 139 (62%) of 224 patients given PC had grade 3-4 adverse events. We noted more grade 3 or higher hypertension (51 [23%] of 222 vs 0) and thrombotic events (13 [6%] of 222 vs 2 [1%] of 224) with PCB than with PC.

INTERPRETATION: Addition of bevacizumab to pemetrexed plus cisplatin significantly improved OS in malignant pleural mesothelioma at the cost of expected manageable toxic effects, therefore it should be considered as a suitable treatment for the disease.

FUNDING: Intergroupe Francophone de Cancérologie Thoracique (IFCT).}, } @article {pmid26715106, year = {2016}, author = {Gilham, C and Rake, C and Burdett, G and Nicholson, AG and Davison, L and Franchini, A and Carpenter, J and Hodgson, J and Darnton, A and Peto, J}, title = {Pleural mesothelioma and lung cancer risks in relation to occupational history and asbestos lung burden.}, journal = {Occupational and environmental medicine}, volume = {73}, number = {5}, pages = {290-299}, pmid = {26715106}, issn = {1470-7926}, support = {MC_UU_12023/21/MRC_/Medical Research Council/United Kingdom ; MR/K006584/1/MRC_/Medical Research Council/United Kingdom ; /CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Adult ; Aged ; Asbestos, Amosite/adverse effects/analysis ; Asbestos, Amphibole/*adverse effects/analysis ; Asbestos, Crocidolite/adverse effects/analysis ; Asbestos, Serpentine/adverse effects/analysis ; Asbestosis/complications ; Employment ; Female ; Humans ; *Lung/chemistry/pathology ; Lung Neoplasms/*chemically induced/pathology ; Male ; Mesothelioma/*chemically induced/pathology ; Mesothelioma, Malignant ; Middle Aged ; Mineral Fibers/adverse effects/analysis ; Occupational Diseases/*chemically induced/pathology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*chemically induced/pathology ; Risk Assessment ; }, abstract = {BACKGROUND: We have conducted a population-based study of pleural mesothelioma patients with occupational histories and measured asbestos lung burdens in occupationally exposed workers and in the general population. The relationship between lung burden and risk, particularly at environmental exposure levels, will enable future mesothelioma rates in people born after 1965 who never installed asbestos to be predicted from their asbestos lung burdens.

METHODS: Following personal interview asbestos fibres longer than 5 µm were counted by transmission electron microscopy in lung samples obtained from 133 patients with mesothelioma and 262 patients with lung cancer. ORs for mesothelioma were converted to lifetime risks.

RESULTS: Lifetime mesothelioma risk is approximately 0.02% per 1000 amphibole fibres per gram of dry lung tissue over a more than 100-fold range, from 1 to 4 in the most heavily exposed building workers to less than 1 in 500 in most of the population. The asbestos fibres counted were amosite (75%), crocidolite (18%), other amphiboles (5%) and chrysotile (2%).

CONCLUSIONS: The approximate linearity of the dose-response together with lung burden measurements in younger people will provide reasonably reliable predictions of future mesothelioma rates in those born since 1965 whose risks cannot yet be seen in national rates. Burdens in those born more recently will indicate the continuing occupational and environmental hazards under current asbestos control regulations. Our results confirm the major contribution of amosite to UK mesothelioma incidence and the substantial contribution of non-occupational exposure, particularly in women.}, } @article {pmid26713662, year = {2016}, author = {Soeberg, MJ and Creighton, N and Currow, DC and Young, JM and van Zandwijk, N}, title = {Patterns in the incidence, mortality and survival of malignant pleural and peritoneal mesothelioma, New South Wales, 1972-2009.}, journal = {Australian and New Zealand journal of public health}, volume = {40}, number = {3}, pages = {255-262}, doi = {10.1111/1753-6405.12503}, pmid = {26713662}, issn = {1753-6405}, mesh = {Adolescent ; Adult ; Age Distribution ; Aged ; Disease-Free Survival ; Drug Therapy, Combination ; Female ; Humans ; Incidence ; Male ; Mesothelioma/drug therapy/*epidemiology/mortality/pathology ; Middle Aged ; New South Wales/epidemiology ; Peritoneal Neoplasms/drug therapy/*epidemiology ; Pleural Neoplasms/drug therapy/*epidemiology ; Registries ; Sex Distribution ; Survival Analysis ; Young Adult ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) and malignant peritoneal mesothelioma (MPeM) are often grouped together in descriptive epidemiological analyses, resulting in limited understanding of epidemiological patterns for these tumour types.

METHODS: We studied patterns in the incidence, mortality and survival of people diagnosed with MPM (n=4,076) and MPeM (n=293) in New South Wales (NSW), Australia, 1972-2009. We also calculated 5-year relative survival for people diagnosed 1972-2006 followed up to 2007. We assessed patterns for each tumour type and histological subtype and, where possible, by combination of these categories.

RESULTS: Annual MPM cases steadily increased over time (n=208 in 2009). There was an increasing trend in the MPM age-standardised incidence rate from 1972 up to 1994. This rate increase has levelled off in the past 10 years. Since 1999, 11 cases of MPeM were diagnosed each year, on average. Five-year relative survival remained stable for MPM and MPeM. However, 5-year relative survival in 2002-2006 was substantially higher for people with MPM epithelioid histological subtype (11.7% [95%CI 6.8-18.2%]) compared to all other non-epithelioid histological subtypes (6.9% [95%CI 5.0-9.1%]), a 70% difference. Survival was also greater for women with MPM (13.4% [95%CI 8.5-19.4%]) compared to men (7.0% [95%CI 5.1-9.2%]).

INTERPRETATION: MPM incidence rates have stabilised since the mid-1990s, suggesting that maximum incidence levels have been reached. When more up-to-date data are available, survival estimates should be reanalysed to include people likely to benefit from the wide introduction of combination chemotherapy in 2007, including pemetrexed.}, } @article {pmid26695618, year = {2015}, author = {Blum, W and Pecze, L and Felley-Bosco, E and Schwaller, B}, title = {Overexpression or absence of calretinin in mouse primary mesothelial cells inversely affects proliferation and cell migration.}, journal = {Respiratory research}, volume = {16}, number = {}, pages = {153}, pmid = {26695618}, issn = {1465-993X}, mesh = {Animals ; Calbindin 2/deficiency/genetics/*metabolism ; Cell Cycle ; *Cell Movement ; *Cell Proliferation ; Cell Shape ; Cells, Cultured ; Epithelial Cells/*metabolism/pathology ; Genotype ; Mesothelin ; Mice, Inbred C57BL ; Mice, Knockout ; Peritoneum/*metabolism/pathology ; Phenotype ; Primary Cell Culture ; RNA Interference ; Signal Transduction ; Time Factors ; Transfection ; Up-Regulation ; }, abstract = {BACKGROUND: The Ca(2+)-binding protein calretinin is currently used as a positive marker for identifying epithelioid malignant mesothelioma (MM) and reactive mesothelium, but calretinin's likely role in mesotheliomagenesis remains unclear. Calretinin protects immortalized mesothelial cells in vitro from asbestos-induced cytotoxicity and thus might be implicated in mesothelioma formation. To further investigate calretinin's putative role in the early steps of MM generation, primary mesothelial cells from calretinin knockout (CR-/-) and wildtype (WT) mice were compared.

METHODS: Primary mouse mesothelial cells from WT and CR-/- mice were investigated with respect to morphology, marker proteins, proliferation, cell cycle parameters and mobility in vitro. Overexpression of calretinin or a nuclear-targeted variant was achieved by a lentiviral expression system.

RESULTS: CR-/- mice have a normal mesothelium and no striking morphological abnormalities compared to WT animals were noted. Primary mouse mesothelial cells from both genotypes show a typical "cobblestone-like" morphology and express mesothelial markers including mesothelin. In cells from CR-/- mice in vitro, we observed more giant cells and a significantly decreased proliferation rate. Up-regulation of calretinin in mesothelial cells of both genotypes increases the proliferation rate and induces a cobblestone-like epithelial morphology. The length of the S/G2/M phase is unchanged, however the G1 phase is clearly prolonged in CR-/- cells. They are also much slower to close a scratch in a confluent cell layer (2D-wound assay). In addition to a change in cell morphology, an increase in proliferation and mobility is observed, if calretinin overexpression is targeted to the nucleus. Thus, both calretinin and nuclear-targeted calretinin increase mesothelial cell proliferation and consequently, speed up the scratch-closure time. The increased rate of scratch closure in WT cells is the result of two processes: an increased proliferation rate and augmented cell mobility of the border cells migrating towards the empty space.

CONCLUSIONS: We hypothesize that the differences in proliferation and mobility between WT and CR-/- mesothelial cells are the likely result from differences in their developmental trajectories. The mechanistic understanding of the function of calretinin and its putative implication in signaling pathways in normal mesothelial cells may help understanding its role during the processes that lead to mesothelioma formation and could possibly open new avenues for mesothelioma therapy, either by directly targeting calretinin expression or indirectly by targeting calretinin-mediated downstream signaling.}, } @article {pmid26692324, year = {2016}, author = {Abakay, A and Tanrikulu, AC and Ayhan, M and Imamoglu, MS and Taylan, M and Kaplan, MA and Abakay, O}, title = {High-risk mesothelioma relation to meteorological and geological condition and distance from naturally occurring asbestos.}, journal = {Environmental health and preventive medicine}, volume = {21}, number = {2}, pages = {82-90}, pmid = {26692324}, issn = {1347-4715}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Breast Neoplasms/chemically induced/epidemiology ; Climate ; *Environmental Exposure ; Female ; Geology ; Humans ; Incidence ; Lung Neoplasms/chemically induced/*epidemiology ; Male ; Mesothelioma/chemically induced/*epidemiology ; Mesothelioma, Malignant ; Middle Aged ; Risk Factors ; Turkey/epidemiology ; Young Adult ; }, abstract = {OBJECTIVES: Very few studies have investigated the incidence and risk of malignant mesothelioma (MM) associated with distinct sources of asbestos exposure, especially exposure to naturally occurring asbestos (NOA).

METHODS: Subjects were MM, lung, and breast cancer patients who were diagnosed and followed in Diyarbakir Province between 2008 and 2013. The birthplaces of patients were displayed on a geologic map. Geological and meteorological effects on MM were analyzed by logistic regression.

RESULTS: A total of 180 MM, 368 breast, and 406 lung cancer patients were included. The median distance from birthplace to ophiolites was 6.26 km for MM, 31.06 km for lung, and 34.31 km for breast cancer (p < 0.001). The majority of MM cases were seen within 20 km from NOA areas. The MM incidence inside of NOA was 1059/100.000, and out of NOA was 397/100.000; this difference was significant (p = 0.014). The largest concentration of MM residential areas was within ± 30° (34 residential areas 36.6%) of the dominant wind direction. Most MM patients were found in or near the dominant wind direction, especially in the acute angle defined by the dominant wind direction. MM incidence was directly proportional to {[area of NOA (km(2))] * [cosine α of wind direction angle]} and was inversely proportional to the square of the distance (R = 0.291, p = 0.023).

CONCLUSIONS: MM was higher near NOA and in the downwind direction. MM incidence and risk were affected by geological and meteorological factors.}, } @article {pmid26689911, year = {2015}, author = {Westbom, C and Thompson, JK and Leggett, A and MacPherson, M and Beuschel, S and Pass, H and Vacek, P and Shukla, A}, title = {Inflammasome Modulation by Chemotherapeutics in Malignant Mesothelioma.}, journal = {PloS one}, volume = {10}, number = {12}, pages = {e0145404}, pmid = {26689911}, issn = {1932-6203}, support = {R01 ES021110/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Antineoplastic Combined Chemotherapy Protocols/*pharmacology ; Carrier Proteins/genetics/*metabolism ; Caspase 1/metabolism ; Cell Line, Tumor/drug effects ; Cisplatin/administration & dosage/pharmacology ; Doxorubicin/pharmacology ; Feedback, Physiological/drug effects ; Humans ; Inflammasomes/*drug effects/metabolism ; Interleukin 1 Receptor Antagonist Protein/administration & dosage/pharmacology ; Interleukin-18/metabolism ; Interleukin-1beta/metabolism ; Lung Neoplasms/*drug therapy/metabolism/pathology ; Male ; Mesothelioma/*drug therapy/metabolism/pathology ; Mesothelioma, Malignant ; Mice, SCID ; NLR Family, Pyrin Domain-Containing 3 Protein ; Receptors, Interleukin-1/antagonists & inhibitors/metabolism ; Xenograft Model Antitumor Assays ; }, abstract = {Malignant mesothelioma (MM) is a fatal disease in dire need of therapy. The role of inflammasomes in cancer is not very well studied, however, literature supports both pro-and anti-tumorigenic effects of inflammasomes on cancer depending upon the type of cancer. Asbestos is a causative agent for MM and we have shown before that it causes inflammasome priming and activation in mesothelial cells. MM tumor cells/tissues showed decreased levels of inflammasome components like NLRP3 and caspase-1 as compared to human mesothelial cells or normal tissue counterpart of tumor. Based on our preliminary findings we hypothesized that treatment of MMs with chemotherapeutic drugs may elevate the levels of NLRP3 and caspase-1 resulting in increased cell death by pyroptosis while increasing the levels of IL-1β and other pro-inflammatory molecules. Therefore, a combined strategy of chemotherapeutic drug and IL-1R antagonist may play a beneficial role in MM therapy. To test our hypothesis we used two human MM tumor cell lines (Hmeso, H2373) and two chemotherapeutic drugs (doxorubicin, cisplatin). Through a series of experiments we showed that both chemotherapeutic drugs caused increases in NLRP3 levels, caspase-1 activation, pyroptosis and pro-inflammatory molecules released from MM cells. In vivo studies using SCID mice and Hmeso cells showed that tumors were smaller in combined treatment group of cisplatin and IL-1R antagonist (Anakinra) as compared to cisplatin alone or untreated control groups. Taken together our study suggests that chemotherapeutic drugs in combination with IL-1R antagonist may have a beneficial role in MM treatment.}, } @article {pmid26689234, year = {2015}, author = {Fujimoto, N and Gemba, K and Aoe, K and Kato, K and Yokoyama, T and Usami, I and Onishi, K and Mizuhashi, K and Yusa, T and Kishimoto, T}, title = {Clinical Investigation of Benign Asbestos Pleural Effusion.}, journal = {Pulmonary medicine}, volume = {2015}, number = {}, pages = {416179}, pmid = {26689234}, issn = {2090-1844}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Asbestosis/complications/diagnosis ; Carcinogens ; Humans ; Lung Neoplasms/complications/diagnosis ; Male ; Middle Aged ; Pleural Diseases/complications/diagnosis ; Pleural Effusion/complications/*diagnostic imaging ; Pulmonary Atelectasis/complications/diagnosis ; Retrospective Studies ; Thoracentesis ; Thoracic Cavity/*chemistry ; Tomography, X-Ray Computed ; }, abstract = {There is no detailed information about benign asbestos pleural effusion (BAPE). The aim of the study was to clarify the clinical features of BAPE. The criteria of enrolled patients were as follows: (1) history of asbestos exposure; (2) presence of pleural effusion determined by chest X-ray, CT, and thoracentesis; and (3) the absence of other causes of effusion. Clinical information was retrospectively analysed and the radiological images were reviewed. There were 110 BAPE patients between 1991 and 2012. All were males and the median age at diagnosis was 74 years. The median duration of asbestos exposure and period of latency for disease onset of BAPE were 31 and 48 years, respectively. Mean values of hyaluronic acid, adenosine deaminase, and carcinoembryonic antigen in the pleural fluid were 39,840 ng/mL, 23.9 IU/L, and 1.8 ng/mL, respectively. Pleural plaques were detected in 98 cases (89.1%). Asbestosis was present in 6 (5.5%) cases, rounded atelectasis was detected in 41 (37.3%) cases, and diffuse pleural thickening (DPT) was detected in 30 (27.3%) cases. One case developed lung cancer (LC) before and after BAPE. None of the cases developed malignant pleural mesothelioma (MPM) during the follow-up.}, } @article {pmid26681974, year = {2015}, author = {Hjerpe, A and Ascoli, V and Bedrossian, C and Boon, M and Creaney, J and Davidson, B and Dejmek, A and Dobra, K and Fassina, A and Field, A and Firat, P and Kamei, T and Kobayashi, T and Michael, CW and Önder, S and Segal, A and Vielh, P}, title = {Guidelines for cytopathologic diagnosis of epithelioid and mixed type malignant mesothelioma. Complementary statement from the International Mesothelioma Interest Group, also endorsed by the International Academy of Cytology and the Papanicolaou Society of Cytopathology.}, journal = {CytoJournal}, volume = {12}, number = {}, pages = {26}, pmid = {26681974}, issn = {0974-5963}, abstract = {To provide practical guidelines for the cytopathologic diagnosis of malignant mesothelioma (MM). Cytopathologists involved in the International Mesothelioma Interest Group (IMIG) and the International Academy of Cytology (IAC), who have an interest in the field contributed to this update. Reference material includes peer-reviewed publications and textbooks. This article is the result of discussions during and after the IMIG 2012 conference in Boston, followed by thorough discussions during the 2013 IAC meeting in Paris. Additional contributions have been obtained from cytopathologists and scientists, who could not attend these meetings, with final discussions and input during the IMIG 2014 conference in cape town. During the previous IMIG biennial meetings, thorough discussions have resulted in published guidelines for the pathologic diagnosis of MM. However, previous recommendations have stated that the diagnosis of MM should be based on histological material only.[12] Accumulating evidence now indicates that the cytological diagnosis of MM supported by ancillary techniques is as reliable as that based on histopathology, although the sensitivity with cytology may be somewhat lower.[345] Recognizing that noninvasive diagnostic modalities benefit both the patient and the health system, future recommendations should include cytology as an accepted method for the diagnosis of this malignancy.[67] The article describes the consensus of opinions of the authors on how cytology together with ancillary testing can be used to establish a reliable diagnosis of MM.}, } @article {pmid26680231, year = {2015}, author = {Robinson, C and Dick, IM and Wise, MJ and Holloway, A and Diyagama, D and Robinson, BW and Creaney, J and Lake, RA}, title = {Consistent gene expression profiles in MexTAg transgenic mouse and wild type mouse asbestos-induced mesothelioma.}, journal = {BMC cancer}, volume = {15}, number = {}, pages = {983}, pmid = {26680231}, issn = {1471-2407}, mesh = {Animals ; Antigens, Viral, Tumor/*genetics/metabolism ; Asbestos/*adverse effects ; Cell Cycle ; Cell Line, Tumor ; E2F Transcription Factors/genetics ; Gene Expression Profiling/*methods ; Gene Expression Regulation, Neoplastic ; Humans ; Mesothelioma/chemically induced/*genetics/pathology ; Mice ; Mice, Transgenic ; Oligonucleotide Array Sequence Analysis/methods ; }, abstract = {BACKGROUND: The MexTAg transgenic mouse model of mesothelioma replicates many aspects of human mesothelioma, including induction by asbestos, pathogenicity and response to cytotoxic chemotherapy, despite high levels of the SV40 large T Antigen (TAg) in the mesothelial compartment. This model enables analysis of the molecular events associated with asbestos induced mesothelioma and is utilised here to investigate the molecular dynamics of tumours induced in these mice, using gene expression patterns as a read out.

METHODS: Gene expression of MexTAg mesothelioma cell lines bearing a high or low number of copies of the TAg transgene were compared to wild type mouse mesotheliomas and normal mouse mesothelial cells using Affymetrix microarray. These data were then compared to a similar published human microarray study using the same platform.

RESULTS: The main expression differences between transgenic mouse and wild type mouse mesotheliomas occurred for genes involved in cell cycle regulation and DNA replication, as would be expected from overexpression of the TAg oncogene. Quantitative PCR confirmed that E2F and E2F regulated genes were significantly more upregulated in MexTAg mesotheliomas and MexTAg mesothelial cells compared to wild type mesotheliomas. Like human mesothelioma, both MexTAg and wild type mesotheliomas had more genes underexpressed than overexpressed compared to normal mouse mesothelial cells. Most notably, the cdkn2 locus was deleted in the wild type mouse mesotheliomas, consistent with 80 % human mesotheliomas, however, this region was not deleted in MexTAg mesotheliomas. Regardless of the presence of TAg, all mouse mesotheliomas had a highly concordant set of deregulated genes compared to normal mesothelial cells that overlapped with the deregulated genes between human mesotheliomas and mesothelial cells.

CONCLUSIONS: This investigation demonstrates that the MexTAg mesotheliomas are comparable with wild type mouse mesotheliomas in their representation of human mesothelioma at the molecular level, with some key gene expression differences that are attributable to the TAg transgene expression. Of particular note, MexTAg mesothelioma development was not dependent on cdkn2 deletion.}, } @article {pmid26678224, year = {2016}, author = {Pietrofesa, RA and Velalopoulou, A and Arguiri, E and Menges, CW and Testa, JR and Hwang, WT and Albelda, SM and Christofidou-Solomidou, M}, title = {Flaxseed lignans enriched in secoisolariciresinol diglucoside prevent acute asbestos-induced peritoneal inflammation in mice.}, journal = {Carcinogenesis}, volume = {37}, number = {2}, pages = {177-187}, pmid = {26678224}, issn = {1460-2180}, support = {1R21AT008291-02/AT/NCCIH NIH HHS/United States ; 1P42ES023720-01/ES/NIEHS NIH HHS/United States ; 1P30 ES013508-02/ES/NIEHS NIH HHS/United States ; R01 CA175691/CA/NCI NIH HHS/United States ; P30 ES013508/ES/NIEHS NIH HHS/United States ; P42 ES023720/ES/NIEHS NIH HHS/United States ; R21 AT008291/AT/NCCIH NIH HHS/United States ; R03 CA180548/CA/NCI NIH HHS/United States ; P30 CA016520/CA/NCI NIH HHS/United States ; R01 CA133470/CA/NCI NIH HHS/United States ; P30 CA006927/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antioxidants/pharmacology ; Asbestos, Crocidolite/*toxicity ; Butylene Glycols/*administration & dosage ; Chromatography, Liquid ; Diet ; Dietary Supplements ; Disease Models, Animal ; Enzyme-Linked Immunosorbent Assay ; Flax ; Glucosides/*administration & dosage ; Inflammation/*pathology ; Lignans/*administration & dosage ; Mesothelioma/pathology ; Mice ; Mice, Mutant Strains ; Oxidative Stress/drug effects ; Peritoneal Lavage ; Peritoneum/drug effects/*pathology ; Precancerous Conditions/drug therapy ; Reverse Transcriptase Polymerase Chain Reaction ; Seeds ; Tandem Mass Spectrometry ; Transcriptome ; }, abstract = {Malignant mesothelioma (MM), linked to asbestos exposure, is a highly lethal form of thoracic cancer with a long latency period, high mortality and poor treatment options. Chronic inflammation and oxidative tissue damage caused by asbestos fibers are linked to MM development. Flaxseed lignans, enriched in secoisolariciresinol diglucoside (SDG), have antioxidant, anti-inflammatory and cancer chemopreventive properties. As a prelude to chronic chemoprevention studies for MM development, we tested the ability of flaxseed lignan component (FLC) to prevent acute asbestos-induced inflammation in MM-prone Nf2(+/mu) mice. Mice (n = 16-17 per group) were placed on control (CTL) or FLC-supplemented diets initiated 7 days prior to a single intraperitoneal bolus of 400 µg of crocidolite asbestos. Three days post asbestos exposure, mice were evaluated for abdominal inflammation, proinflammatory/profibrogenic cytokine release, WBC gene expression changes and oxidative and nitrosative stress in peritoneal lavage fluid (PLF). Asbestos-exposed mice fed CTL diet developed acute inflammation, with significant (P < 0.0001) elevations in WBCs and proinflammatory/profibrogenic cytokines (IL-1ß, IL-6, TNFα, HMGB1 and active TGFß1) relative to baseline (BL) levels. Alternatively, asbestos-exposed FLC-fed mice had a significant (P < 0.0001) decrease in PLF WBCs and proinflammatory/profibrogenic cytokine levels relative to CTL-fed mice. Importantly, PLF WBC gene expression of cytokines (IL-1ß, IL-6, TNFα, HMGB1 and TGFß1) and cytokine receptors (TNFαR1 and TGFßR1) were also downregulated by FLC. FLC also significantly (P < 0.0001) blunted asbestos-induced nitrosative and oxidative stress. FLC reduces acute asbestos-induced peritoneal inflammation, nitrosative and oxidative stress and may thus prove to be a promising agent in the chemoprevention of MM.}, } @article {pmid26659652, year = {2016}, author = {Silvestri, S and Di Benedetto, F and Raffaell, C and Veraldi, A}, title = {Asbestos in toys: an exemplary case.}, journal = {Scandinavian journal of work, environment & health}, volume = {42}, number = {1}, pages = {80-85}, doi = {10.5271/sjweh.3542}, pmid = {26659652}, issn = {1795-990X}, mesh = {Aluminum Silicates/history/*toxicity ; Art/history ; Asbestos/history/*toxicity ; Clay ; Consumer Product Safety ; Europe ; Female ; History, 20th Century ; History, 21st Century ; Humans ; Male ; Mesothelioma/epidemiology/etiology ; Occupational Diseases/etiology ; Occupational Exposure/adverse effects ; Play and Playthings/*injuries ; School Teachers ; }, abstract = {OBJECTIVES: DAS was an artificial clay which, once molded, hardened at room temperature. It was largely used as a toy between 1963 and 1975 in Italy, Netherlands, Germany, UK and Norway. This case report describes and reports the presence of asbestos in DAS.

METHODS: We investigated the presence of asbestos in DAS using light and electron microscopy on samples of the original material. We searched administrative documents at the State Archive of Turin and conducted interviews with past employees on annual production, suppliers, and purchasers.

RESULTS: The analytical tests confirmed the presence of asbestos fibers in DAS: about 30% of its composition. The documents found at the State Archive confirmed the annual purchase of hundreds tons of raw asbestos from the Amiantifera di Balangero, the Italian asbestos mine. DAS was found to be used also within craftsmanship.

CONCLUSIONS: Asbestos fibers in DAS may have caused exposure to production workers and a variety of users, including artists, teachers, and children. Over 13 years, about 55 million packs of DAS were produced and sold. The number of users is difficult to estimate but may have been in the order of millions. In Italy, a specific question on the use of DAS has been included in a routinely used mesothelioma questionnaire. As DAS was exported to other countries, our findings suggest that mesothelioma patients should be asked about their past use of DAS, in particular individuals not reporting a clear past asbestos exposure. Additionally, this discovery shows the incompleteness of records on asbestos uses and suggests to test items, including toys, imported from countries where asbestos is not forbidden.}, } @article {pmid26655961, year = {2016}, author = {Lambert, CS and Alexander, BH and Ramachandran, G and MacLehose, RF and Nelson, HH and Ryan, AD and Mandel, JH}, title = {A case-control study of mesothelioma in Minnesota iron ore (taconite) miners.}, journal = {Occupational and environmental medicine}, volume = {73}, number = {2}, pages = {103-109}, pmid = {26655961}, issn = {1470-7926}, support = {T32 HL007741/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; Air Pollutants, Occupational/adverse effects ; Case-Control Studies ; Employment ; Female ; Ferric Compounds/adverse effects ; Humans ; Iron/*adverse effects ; Logistic Models ; Lung Neoplasms/*etiology/mortality ; Male ; Mesothelioma/*etiology/mortality ; Minerals ; *Mining ; Minnesota/epidemiology ; Occupational Diseases/*etiology/mortality ; Occupational Exposure/*adverse effects ; Particulate Matter/*adverse effects ; Risk Factors ; Silicates/*adverse effects ; Work ; }, abstract = {OBJECTIVES: An excess of mesothelioma has been observed in iron ore miners in Northeastern Minnesota. Mining and processing of taconite iron ore generate exposures that include elongate mineral particles (EMPs) of amphibole and non-amphibole origin. We conducted a nested case-control study of mesothelioma in a cohort of 68,737 iron ore miners (haematite and taconite ore miners) to evaluate the association between mesothelioma, employment and EMP exposures from taconite mining.

METHODS: Mesothelioma cases (N=80) were identified through the Minnesota Cancer Surveillance System (MCSS) and death certificates. Four controls of similar age were selected for each case with 315 controls ultimately eligible for inclusion. Mesothelioma risk was evaluated by estimating rate ratios and 95% CIs with conditional logistic regression in relation to duration of taconite industry employment and cumulative EMP exposure [(EMP/cc)×years], defined by the National Institute for Occupational Safety and Health (NIOSH) 7400 method. Models were adjusted for employment in haematite mining and potential exposure to commercial asbestos products used in the industry.

RESULTS: All mesothelioma cases were male and 57 of the cases had work experience in the taconite industry. Mesothelioma was associated with the number of years employed in the taconite industry (RR=1.03, 95% CI 1.00 to 1.06) and cumulative EMP exposure (RR=1.10, 95% CI 0.97 to -1.24). No association was observed with employment in haematite mining.

CONCLUSIONS: These results support an association between mesothelioma and employment duration and possibly EMP exposure in taconite mining and processing. The type of EMP was not determined. The potential role of commercial asbestos cannot be entirely ruled out.}, } @article {pmid26645426, year = {2016}, author = {Liang, YF and Zheng, GQ and Chen, YF and Song, H and Yin, WJ and Zhang, L}, title = {CT differentiation of diffuse malignant peritoneal mesothelioma and peritoneal carcinomatosis.}, journal = {Journal of gastroenterology and hepatology}, volume = {31}, number = {4}, pages = {709-715}, doi = {10.1111/jgh.13260}, pmid = {26645426}, issn = {1440-1746}, mesh = {Carcinoma/*diagnostic imaging/pathology ; Diagnosis, Differential ; Female ; Humans ; Lymph Nodes/diagnostic imaging/pathology ; Male ; Mesentery/diagnostic imaging/pathology ; Mesothelioma/*diagnostic imaging/pathology ; Middle Aged ; Omentum/diagnostic imaging/pathology ; Peritoneal Neoplasms/*diagnostic imaging/pathology ; Peritoneum/diagnostic imaging/pathology ; Retrospective Studies ; *Tomography, X-Ray Computed ; }, abstract = {BACKGROUND AND AIM: Diffuse malignant peritoneal mesothelioma (DMPM) and peritoneal carcinomatosis (PC) have similar imaging in computer tomography (CT). We aimed to distinguish them.

METHODS: Computer tomography findings were evaluated in 48 DMPM and 47 PC for the peritoneal, mesenteric, omentum, lymph nodes, viscera infiltration, ascites and pleural plaques.

RESULTS: Two groups had no difference in terms of thickness, clinical manifestation, diameter of lymph nodes, ascites, and viscera infiltration. But they showed differences in the following: Ratio of asbestos exposure in DMPM group was higher. Smooth and irregular peritoneal thickening were more seen in DMPM group; peritoneal nodules were more commonly detected in PC group. Forty-eight cases of peritoneum in DMPM showed mild enhanced, while 14 patients in PC showed severe enhanced. Nodular type of omentum was more common in PC group than in DMPM group; omental cake was more commonly detected in DMPM group. Mesentery involvement was more commonly seen in DMPM group. Location of enlarged lymph nodes in cardiophrenic region was more frequently identified in DMPM, whereas location of enlarged lymph nodes in retroperitoneal region was more frequently identified in PC. Lymph nodes fusion was more frequently visualized in PC. Fixation of the intestinal wall was more common in DMPM. Pleural plaque was more common in DMPM. PC had distant metastasis except primary foci and peritoneum. In PC, tumor origins were ovary in 10, digestive system in 21, breast in one.

CONCLUSION: Using a combination of CT findings may increase our ability to distinguish PC from DMPM.}, } @article {pmid26638921, year = {2015}, author = {Rapisarda, V and Ledda, C and Migliore, M and Salemi, R and Musumeci, A and Bracci, M and Marconi, A and Loreto, C and Libra, M}, title = {FBLN-3 as a biomarker of pleural plaques in workers occupationally exposed to carcinogenic fibers: a pilot study.}, journal = {Future oncology (London, England)}, volume = {11}, number = {24 Suppl}, pages = {35-37}, doi = {10.2217/fon.15.271}, pmid = {26638921}, issn = {1744-8301}, mesh = {Asbestos, Amphibole/adverse effects ; Biomarkers/*blood ; Carcinogens/*toxicity ; Environmental Exposure/adverse effects ; Extracellular Matrix Proteins/*blood ; Humans ; Italy ; Lung Neoplasms/*blood/*chemically induced ; Male ; Mesothelioma/*blood/*chemically induced ; Mesothelioma, Malignant ; Middle Aged ; Pilot Projects ; Pleural Neoplasms/*blood/*chemically induced ; }, abstract = {FBLN-3 has recently been proposed as a biomarker for malignant mesothelioma. A significantly increased standardized mortality rate from malignant mesothelioma has been reported in Biancavilla, Italy. Its cause has been identified in environmental exposure to fluoro-edenite. The aim of this study was to seek a correlation between plasma FBLN-3 concentration and pleural plaques in subjects exposed to fluoro-edenite and in a nonexposed control group. Pleural plaques was never detected in the control group, whereas it was found in 52% of exposed subjects. Median FBLN-3 concentrations were 12.96 and 5.29 ng/ml in the exposed and the control group, respectively (p < 0.001). FBLN-3 plasma levels exhibited a high predictive value for the presence of pleural plaques.}, } @article {pmid26638917, year = {2015}, author = {Rintoul, RC}, title = {The MesoVATS trial: is there a future for video-assisted thoracoscopic surgery partial pleurectomy?.}, journal = {Future oncology (London, England)}, volume = {11}, number = {24 Suppl}, pages = {15-17}, doi = {10.2217/fon.15.274}, pmid = {26638917}, issn = {1744-8301}, mesh = {Aged ; Clinical Trials as Topic ; Female ; Humans ; Lung Neoplasms/*pathology ; Male ; Mesothelioma/*pathology ; Mesothelioma, Malignant ; Multicenter Studies as Topic ; Pleural Neoplasms/*pathology ; Quality of Life ; Randomized Controlled Trials as Topic ; Thoracic Surgery, Video-Assisted/methods ; }, abstract = {Malignant pleural mesothelioma, a uniformly fatal cancer caused by prior asbestos exposure, places a major burden on society. The MesoVATS trial was a multicenter randomized controlled trial that examined the role of video-assisted thoracoscopic partial pleurectomy (VAT-PP) versus talc pleurodesis in patients with malignant pleural mesothelioma. Overall there was no difference in survival between VAT-PP and talc pleurodesis. VAT-PP resulted in more complications, longer hospital stay and was more expensive. However, there was some evidence that VAT-PP improved EQ5D measured quality of life after 6 months particularly in the European Organisation for Research and Treatment of Cancer low-risk subgroup. At present the future role of VAT-PP is uncertain and may merit further investigation but this should be within the context of clinical trials. VAT-PP may also have a role to play in the specific situation of trapped lung.}, } @article {pmid26638914, year = {2015}, author = {Treasure, T}, title = {The Second Mediterranean Symposium: considering mesothelioma from a local and international perspective.}, journal = {Future oncology (London, England)}, volume = {11}, number = {24 Suppl}, pages = {5-6}, doi = {10.2217/fon.15.259}, pmid = {26638914}, issn = {1744-8301}, mesh = {Humans ; Internationality ; Mesothelioma/*pathology ; Pleural Neoplasms/*pathology ; }, } @article {pmid26638913, year = {2015}, author = {Migliore, M}, title = {Opening lecture to the Second Mediterranean Symposium in Thoracic Oncology. Foreword.}, journal = {Future oncology (London, England)}, volume = {11}, number = {24 Suppl}, pages = {1-3}, doi = {10.2217/fon.15.280}, pmid = {26638913}, issn = {1744-8301}, mesh = {Humans ; Medical Oncology/methods ; Mediterranean Region ; Thoracic Neoplasms/*pathology ; }, } @article {pmid26621064, year = {2015}, author = {Zocchetti, C}, title = {[Mesothelioma and acceleration].}, journal = {La Medicina del lavoro}, volume = {106}, number = {6}, pages = {431-446}, pmid = {26621064}, issn = {0025-7818}, mesh = {Adult ; Age Distribution ; Age of Onset ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; *Carcinogens ; Case-Control Studies ; Humans ; Italy/epidemiology ; Kinetics ; Lung Neoplasms/epidemiology/*etiology ; Mesothelioma/epidemiology/*etiology ; Middle Aged ; Occupational Exposure/*adverse effects ; Risk Assessment ; Risk Factors ; }, abstract = {INTRODUCTION: Taking a publication by Berry in 2007 (3) as a cue, this paper presents in didactic form the topic of acceleration of events as a consequence of a harmful exposure and extends the proposed approach to the case of the asbestos-mesothelioma relationship.

METHODS: Berry's approach was applied to lung cancer and mesothelioma data.

RESULTS: The effects of the acceleration of events are presented as a function of age at onset in exposed subjects, relative risk, scale factor, in addition to age and geographical variability of the relationship between age and mesothelioma rates.

DISCUSSION: The discussion regards the general characteristics of the method of acceleration, its meaning and interpretation, and the difficulties associated with its application in the context of diseases with low occurrence; the conditions, applicability constraints, and specific results in the case of mesothelioma; the epidemiologic meaning of acceleration and the difficulties of its extension to individual subjects.}, } @article {pmid26620209, year = {2016}, author = {Yamagishi, T and Fujimoto, N and Miyamoto, Y and Asano, M and Fuchimoto, Y and Wada, S and Kitamura, K and Ozaki, S and Nishi, H and Kishimoto, T}, title = {Brain metastases in malignant pleural mesothelioma.}, journal = {Clinical & experimental metastasis}, volume = {33}, number = {3}, pages = {231-237}, pmid = {26620209}, issn = {1573-7276}, mesh = {Aged ; Brain Neoplasms/mortality/*secondary ; Humans ; Kaplan-Meier Estimate ; Lung Neoplasms/mortality/*secondary ; Male ; Mesothelioma/mortality/*secondary ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/mortality/*pathology ; Prognosis ; Retrospective Studies ; Risk Factors ; }, abstract = {The brain is a rare site of metastasis in malignant pleural mesothelioma (MPM), and its clinical features and prognosis remain unclear. The aim of this study was to investigate the incidence, prognosis, and risk factors for brain metastases (BM) in MPM patients. Between July 1993 and October 2014, 150 patients with histologically proven MPM were included in this retrospective study. The cumulative incidence of BM was estimated with the Kaplan-Meier method, and differences between groups were analyzed by the log-rank test. Multivariate logistic regression analysis was applied to assess risk factors for BM. The median follow-up time was 11 months (range 0-154.0 months). A total of eight patients (5.3 %) developed BM during the course of their illness. Multivariate analysis identified age <65 years (odds ratio [OR] = 5.83, p = 0.038) and International Mesothelioma Interest Group stage IV (OR = 1.69, p = 0.040) as independent factors related to increased risk of developing BM. The 1-and 2-year cumulative rates of BM were 4.0 % (95 % confidence intervals [CI] 1.4-8.5 %) and 5.3 % (95 % CI 2.3-10.2 %), respectively. Our study showed that the overall survival (OS) of patients with BM was worse than that of patients without BM (median OS 6.5 vs. 11.0 months, p = 0.037). The prognosis for BM in MPM patients is poor. Clinicians should perform careful screening for BM, especially in patients with risk factors.}, } @article {pmid26600776, year = {2015}, author = {Yaguchi, D and Ichikawa, M and Inoue, N and Kobayashi, D and Matsuura, A and Shizu, M and Imai, N and Watanabe, K}, title = {An Autopsied Case of Malignant Sarcomatoid Pleural Mesothelioma in Which Chest Pain Developed Several Months Earlier without Abnormality on Imaging.}, journal = {Case reports in oncology}, volume = {8}, number = {3}, pages = {439-446}, pmid = {26600776}, issn = {1662-6575}, abstract = {The patient experienced chest pain for about 7 months, but a diagnosis could not be made until after death. He was diagnosed with malignant sarcomatoid pleural mesothelioma on autopsy. In this case report, difficult aspects of the diagnosis are discussed. The 70-year-old Japanese man was a driver who transported ceramic-related products. Right chest pain developed in July 2013, but no abnormality was detected on a chest computed tomography (CT) performed in September 2013, and the pain was managed as right intercostal neuralgia. A chest CT performed in late October 2013 revealed a right pleural effusion, and the patient was referred to our hospital in early November 2013. Thoracentesis was performed, but the cytology was negative, and no diagnosis could be made. Close examination was postponed because the patient developed a subarachnoid hemorrhage. He underwent (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) after discharge from the neurosurgery department, and extensive right pleural thickening and (18)F-FDG accumulation in this region were observed. Based on these findings, malignant pleural mesothelioma was suspected, and a thoracoscopy was performed under local anesthesia in early December 2013, but no definite diagnosis could be made. The patient selected best supportive care and died about 7 months after the initial development of right chest pain. The disease was definitively diagnosed as malignant sarcomatoid pleural mesothelioma by a pathological autopsy. When chronic chest pain of unknown cause is observed and past exposure to asbestos is suspected, actions to prevent delay in diagnosis should be taken, including testing for suspicion of malignant pleural mesothelioma.}, } @article {pmid26568009, year = {2015}, author = {Ushio, R and Yamamoto, M and Shibata, Y and Ishii, H and Watanabe, K and Takahashi, R and Sato, T and Kudo, M and Miyake, A and Kaneko, T and Ishigatsubo, Y}, title = {An Autopsy Case Report of Malignant Pleural Mesothelioma with Deciduoid Features.}, journal = {Internal medicine (Tokyo, Japan)}, volume = {54}, number = {22}, pages = {2915-2917}, doi = {10.2169/internalmedicine.54.4940}, pmid = {26568009}, issn = {1349-7235}, mesh = {Aged ; Antineoplastic Combined Chemotherapy Protocols ; Asbestos/*adverse effects ; Autopsy ; Disease Progression ; Fatal Outcome ; Humans ; Lung Neoplasms/diagnosis/*pathology ; Male ; Mesothelioma/diagnosis/*pathology ; Mesothelioma, Malignant ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/diagnosis/*pathology ; }, abstract = {Deciduoid mesothelioma is a rare variant of epithelioid mesothelioma. We experienced the case of a 73-year-old man with asbestos exposure who was diagnosed with malignant pleural mesothelioma with deciduoid features. He received chemotherapy containing six cycles of cisplatin and pemetrexed and survived for twenty-five months after the diagnosis. At autopsy, the final diagnosis was biphasic pleural mesothelioma. Cells with deciduoid features had mostly disappeared, and spindle cells markedly proliferated. To the best of our knowledge, this is the first autopsy case of malignant pleural mesothelioma with deciduoid features that exhibited a response to chemotherapy.}, } @article {pmid26566053, year = {2016}, author = {Capella, S and Bellis, D and Belluso, E}, title = {Diagnosis of Asbestos-Related Diseases: The Mineralogist and Pathologist's Role in Medicolegal Field.}, journal = {The American journal of forensic medicine and pathology}, volume = {37}, number = {1}, pages = {24-28}, doi = {10.1097/PAF.0000000000000206}, pmid = {26566053}, issn = {1533-404X}, mesh = {Asbestos/*analysis ; Asbestosis/*diagnosis ; Humans ; Lung/chemistry/pathology/ultrastructure ; Lung Neoplasms/*diagnosis ; Mesothelioma/*diagnosis ; Microscopy, Electron, Scanning ; Mineral Fibers/analysis ; Pleural Neoplasms/*diagnosis ; Retrospective Studies ; Spectrometry, X-Ray Emission ; }, abstract = {Because asbestos diseases represent a complex pattern of legal, social, and political issue, the involvement of the mineralogist and pathologist for a multidisciplinary assessment of its diagnosis helps investigate the relationship between mesothelioma or lung cancer and occupational or environmental asbestos exposure.In the present study, we consider the concentrations of asbestos bodies (ABs) detected by optical microscopy (OM) and scanning electron microscopy (SEM) and the burden of different kinds of mineral fibers (among which is asbestos) identified by SEM combined with an energy dispersive spectrometer (EDS), in 10 lung tissue samples of subjects with occupational and nonoccupational exposure to asbestos.In all subjects with occupational exposure to asbestos, more than 1000 ABs per gram of dry weight were detected both with OM and SEM; this concentration is internationally accepted as suggesting high probability of past occupational exposure to asbestos.In 9 lung samples of the 10 investigated by SEM-EDS different inorganic fibers were found. Asbestos fibers have been identified too, and more than 100,000 fibers per gram of dry weight were detected in subjects with occupational exposure; this concentration is internationally accepted as suggesting high probability of past occupational exposure to asbestos.Instead, when the ABs burden is low or moderate (such as in subjects with absent or probable asbestos exposure), the correlation between ABs concentration determined by OM and those determined by SEM is lost. Therefore, when the ABs value in OM is borderline, the SEM investigation became essential. Furthermore, the mineralogical analysis by SEM-EDS (identification and quantification of inorganic fibers in general and asbestos in particular) of the fibers detected in the lung tissues is very useful, if not necessary, to complete the pathological diagnosis of asbestos-related malignancies in medicolegal field.}, } @article {pmid26552696, year = {2016}, author = {Stayner, LT}, title = {Para-occupational exposures to asbestos: lessons learned from Casale Monferrato, Italy.}, journal = {Occupational and environmental medicine}, volume = {73}, number = {3}, pages = {145-146}, doi = {10.1136/oemed-2015-103233}, pmid = {26552696}, issn = {1470-7926}, mesh = {Asbestos/*adverse effects ; *Carcinogens ; Environmental Exposure/*adverse effects ; Environmental Pollution/*adverse effects ; Female ; Humans ; Lung Neoplasms/*etiology ; Male ; Mesothelioma/*etiology ; Pleural Neoplasms/*etiology ; }, } @article {pmid26530353, year = {2016}, author = {You, BR and Park, WH}, title = {Auranofin induces mesothelioma cell death through oxidative stress and GSH depletion.}, journal = {Oncology reports}, volume = {35}, number = {1}, pages = {546-551}, doi = {10.3892/or.2015.4382}, pmid = {26530353}, issn = {1791-2431}, mesh = {Apoptosis ; Auranofin/*pharmacology ; Caspases/metabolism ; Cell Line, Tumor ; Cell Survival/drug effects ; Gene Expression Regulation, Neoplastic/drug effects ; Glutathione/*metabolism ; Humans ; Mesothelioma/*metabolism ; Oxidative Stress/*drug effects ; Thioredoxin Reductase 1/metabolism ; }, abstract = {Mesothelioma is an aggressive tumor associated with asbestos exposure. Auranofin as an inhibitor of thioredoxin reductase (TrxR) affects many biological processes such as inflammation and proliferation. In the present study, we investigated the cellular effects of auranofin on patient-derived mesothelioma cells in relation to reactive oxygen species (ROS) and glutathione (GSH) levels. Basal TrxR1 levels have no difference between mesothelial cells and certain mesothelioma cells. In particular, ADA, CON and Hmeso mesothelioma cells showed lower levels of TrxR1 expression. Auranofin inhibited the proliferation of mesothelioma cells in a dose-dependent manner. Among mesothelioma cells were ADA and CON cells sensitive to auranofin. This agent also induced caspase-independent apoptosis and necrosis in ADA cells. In addition, auranofin increased ROS levels including O2(•-) and induced GSH depletion in mesothelioma cells. While N-acetyl cysteine (NAC) prevented cell death and decreased ROS levels in auranofin-treated mesothelioma cells, L-buthionine sulfoximine (BSO) intensified apoptosis and GSH depletion in these cells. In conclusion, auranofin induced mesothelioma cell death through oxidative stress and the death was regulated by the status of GSH content.}, } @article {pmid26513124, year = {2016}, author = {Kim, SY and Kim, YC and Kim, Y and Hong, WH}, title = {Predicting the mortality from asbestos-related diseases based on the amount of asbestos used and the effects of slate buildings in Korea.}, journal = {The Science of the total environment}, volume = {542}, number = {Pt A}, pages = {1-11}, doi = {10.1016/j.scitotenv.2015.10.115}, pmid = {26513124}, issn = {1879-1026}, mesh = {*Asbestos ; Asbestos, Serpentine ; Asbestosis/*mortality ; Humans ; Industry ; Lung Neoplasms/*mortality ; Mesothelioma/*mortality ; Occupational Exposure/*statistics & numerical data ; Republic of Korea/epidemiology ; }, abstract = {Asbestos has been used since ancient times, owing to its heat-resistant, rot-proof, and insulating qualities, and its usage rapidly increased after the industrial revolution. In Korea, all slates were previously manufactured in a mixture of about 90% cement and 10% chrysotile (white asbestos). This study used a Generalized Poisson regression (GPR) model after creating databases of the mortality from asbestos-related diseases and of the amount of asbestos used in Korea as a means to predict the future mortality of asbestos-related diseases and mesothelioma in Korea. Moreover, to predict the future mortality according to the effects of slate buildings, a comparative analysis based on the result of the GPR model was conducted after creating databases of the amount of asbestos used in Korea and of the amount of asbestos used in making slates. We predicted the mortality from asbestos-related diseases by year, from 2014 to 2036, according to the amount of asbestos used. As a result, it was predicted that a total of 1942 people (maximum, 3476) will die by 2036. Moreover, based on the comparative analysis according to the influence index, it was predicted that a maximum of 555 people will die from asbestos-related diseases by 2031 as a result of the effects of asbestos-containing slate buildings, and the mortality was predicted to peak in 2021, with 53 cases. Although mesothelioma and pulmonary asbestosis were considered as asbestos-related diseases, these are not the only two diseases caused by asbestos. However the results of this study are highly important and relevant, as, for the first time in Korea, the future mortality from asbestos-related diseases was predicted. These findings are expected to contribute greatly to the Korean government's policies related to the compensation for asbestos victims.}, } @article {pmid26511746, year = {2016}, author = {Barber, CM and Wiggans, RE and Young, C and Fishwick, D}, title = {UK asbestos imports and mortality due to idiopathic pulmonary fibrosis.}, journal = {Occupational medicine (Oxford, England)}, volume = {66}, number = {2}, pages = {106-111}, pmid = {26511746}, issn = {1471-8405}, mesh = {Age Distribution ; *Asbestos ; Asbestosis/*mortality/physiopathology ; Carcinogens ; Construction Materials/*adverse effects ; Female ; Humans ; Idiopathic Pulmonary Fibrosis/*mortality/physiopathology ; Lung Neoplasms/*mortality/physiopathology ; Male ; Mesothelioma/*mortality/physiopathology ; Occupational Diseases/chemically induced/*mortality ; Occupational Exposure/prevention & control/*statistics & numerical data ; Prevalence ; Registries ; United Kingdom/epidemiology ; }, abstract = {BACKGROUND: Previous studies have demonstrated that the rising mortality due to mesothelioma and asbestosis can be predicted from historic asbestos usage. Mortality due to idiopathic pulmonary fibrosis (IPF) is also rising, without any apparent explanation.

AIMS: To compare mortality due to these conditions and examine the relationship between mortality and national asbestos imports.

METHODS: Mortality data for IPF and asbestosis in England and Wales were available from the Office for National Statistics. Data for mesothelioma deaths in England and Wales and historic UK asbestos import data were available from the Health & Safety Executive. The numbers of annual deaths due to each condition were plotted separately by gender, against UK asbestos imports 48 years earlier. Linear regression models were constructed.

RESULTS: For mesothelioma and IPF, there was a significant linear relationship between the number of male and female deaths each year and historic UK asbestos imports. For asbestosis mortality, a similar relationship was found for male but not female deaths. The annual numbers of deaths due to asbestosis in both sexes were lower than for IPF and mesothelioma.

CONCLUSIONS: The strength of the association between IPF mortality and historic asbestos imports was similar to that seen in an established asbestos-related disease, i.e. mesothelioma. This finding could in part be explained by diagnostic difficulties in separating asbestosis from IPF and highlights the need for a more accurate method of assessing lifetime occupational asbestos exposure.}, } @article {pmid26505785, year = {2015}, author = {Ying, C and Maeda, M and Nishimura, Y and Kumagai-Takei, N and Hayashi, H and Matsuzaki, H and Lee, S and Yoshitome, K and Yamamoto, S and Hatayama, T and Otsuki, T}, title = {Enhancement of regulatory T cell-like suppressive function in MT-2 by long-term and low-dose exposure to asbestos.}, journal = {Toxicology}, volume = {338}, number = {}, pages = {86-94}, doi = {10.1016/j.tox.2015.10.005}, pmid = {26505785}, issn = {1879-3185}, mesh = {Asbestos, Serpentine/*toxicity ; CTLA-4 Antigen/metabolism ; Cell Communication/drug effects ; Cell Line, Transformed ; Cell Transformation, Viral ; Coculture Techniques ; Forkhead Transcription Factors/metabolism ; Glucocorticoid-Induced TNFR-Related Protein/metabolism ; Human T-lymphotropic virus 1/pathogenicity ; Humans ; Interleukin-10/genetics/metabolism ; Lymphocyte Activation/*drug effects ; Phenotype ; RNA Interference ; T-Lymphocytes, Regulatory/*drug effects/immunology/metabolism/virology ; Time Factors ; Transfection ; Transforming Growth Factor beta1/genetics/metabolism ; Tumor Escape/drug effects ; }, abstract = {Asbestos exposure causes lung fibrosis and various malignant tumors such as lung cancer and malignant mesothelioma. The effects of asbestos on immune cells have not been thoroughly investigated, although our previous reports showed that asbestos exposure reduced anti-tumor immunity. The effects of continuous exposure of regulatory T cells (Treg) to asbestos were examined using the HTLV-1 immortalized human T cell line MT-2, which possesses a suppressive function and expresses the Treg marker protein, Foxp3. Sublines were generated by the continuous exposure to low doses of asbestos fibers for more than one year. The sublines exposed to asbestos showed enhanced suppressive Treg function via cell-cell contact, and increased production of soluble factors such as IL-10 and transforming growth factor (TGF)-β1. These results also indicated that asbestos exposure induced the reduction of anti-tumor immunity, and efforts to develop substances to reverse this reduction may be helpful in preventing the occurrence of asbestos-induced tumors.}, } @article {pmid26489154, year = {2015}, author = {Nakanishi, N and Shiojiri, M and Inoue, K and Moritaka, T}, title = {[A CASE OF NON-TUBERCULOUS MYCOBACTERIOSIS WITH PLEURAL EFFUSION AND THICKENING IN A PATIENT WITH AN OCCUPATIONAL HISTORY OF ASBESTOS EXPOSURE].}, journal = {Kekkaku : [Tuberculosis]}, volume = {90}, number = {5}, pages = {503-506}, pmid = {26489154}, issn = {0022-9776}, mesh = {Aged ; *Asbestos ; Humans ; Male ; Mycobacterium avium-intracellulare Infection/*diagnosis ; *Occupational Exposure ; Pleurisy/*diagnosis ; }, abstract = {We report a case of a 75-year-old man with pleural effusion and an occupational history of asbestos exposure. Fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET/CT) examination revealed FDG up-takes along his pleura, leading to an initial suspicion of pleural mesothelioma. Pathological findings of a diagnostic video-associated pleural biopsy showed epithelioid cell granuloma. Repeated sputum cultures were positive for Mycobacterium intracellulare. The patient was diagnosed with pleuritis caused by non-tuberculous mycobacteria (NTM). NTM should be considered a potential cause of pleuritis.}, } @article {pmid26481865, year = {2016}, author = {Signorelli, D and Macerelli, M and Proto, C and Vitali, M and Cona, MS and Agustoni, F and Zilembo, N and Platania, M and Trama, A and Gallucci, R and Ganzinelli, M and Pelosi, G and Pastorino, U and de Braud, F and Garassino, MC and Lo Russo, G}, title = {Systemic approach to malignant pleural mesothelioma: what news of chemotherapy, targeted agents and immunotherapy?.}, journal = {Tumori}, volume = {102}, number = {1}, pages = {18-30}, doi = {10.5301/tj.5000436}, pmid = {26481865}, issn = {2038-2529}, mesh = {Angiogenesis Inhibitors/therapeutic use ; Antineoplastic Agents/pharmacology/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Asbestos/toxicity ; Carcinogens/toxicity ; Clinical Trials as Topic ; ErbB Receptors/antagonists & inhibitors ; GPI-Linked Proteins/antagonists & inhibitors ; Histone Deacetylase Inhibitors/therapeutic use ; Humans ; *Immunotherapy/methods ; Lung Neoplasms/chemically induced/*drug therapy/immunology/metabolism/pathology ; Mesothelin ; Mesothelioma/chemically induced/*drug therapy/immunology/metabolism/pathology ; Mesothelioma, Malignant ; *Molecular Targeted Therapy/methods ; Pleural Neoplasms/chemically induced/*drug therapy/immunology/metabolism/pathology ; Proteasome Inhibitors/therapeutic use ; }, abstract = {Malignant pleural mesothelioma is a rare cancer with a cause-effect relationship to asbestos exposure. The prognosis is poor and chemotherapy seems the best treatment option. In the last two decades a deeper understanding of mesothelioma carcinogenesis and invasiveness mechanisms has prompted research efforts to test new agents in patients with malignant pleural mesothelioma, but the results have been modest. Attractive preclinical data disappointed in subsequent experimental phases. Other promising agents failed to improve patient outcomes due to high toxicity. Interesting suggestions have come from preliminary data on immunotherapy. Several trials are ongoing and the results are eagerly awaited. The aim of this review is to discuss the most recent news on systemic therapy for advanced malignant pleural mesothelioma.}, } @article {pmid26467803, year = {2016}, author = {Rintoul, RC and Rassl, DM and Gittins, J and Marciniak, SJ and , }, title = {MesobanK UK: an international mesothelioma bioresource.}, journal = {Thorax}, volume = {71}, number = {4}, pages = {380-382}, doi = {10.1136/thoraxjnl-2015-207496}, pmid = {26467803}, issn = {1468-3296}, support = {MC_U132685863/MRC_/Medical Research Council/United Kingdom ; PB-PG-0213-30098/DH_/Department of Health/United Kingdom ; ETM/285/CSO_/Chief Scientist Office/United Kingdom ; 100140/WT_/Wellcome Trust/United Kingdom ; MCCC-RP-14-A17178/MCCC_/Marie Curie/United Kingdom ; G0601840/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Biological Specimen Banks/*organization & administration/standards/trends ; Biomedical Research/organization & administration ; Foundations/organization & administration ; Humans ; *International Cooperation ; *Lung Neoplasms/economics ; *Mesothelioma/economics ; Mesothelioma, Malignant ; *Pleural Neoplasms/economics ; United Kingdom ; }, abstract = {Malignant pleural mesothelioma causes the greatest societal burden of all the asbestos-related diseases. Progress in better understanding tumour biology will be facilitated by the availability of quality-assured annotated tissue. MesobanK has been created to establish a bioresource of pleural mesothelioma tissue linked to detailed anonymised clinical data. When complete, the bioresource will comprise a 750-patient tissue microarray and prospectively collected tissue, blood and pleural fluid from 300 patients with mesothelioma. Twenty-six new cell lines have also been developed. MesobanK meets all appropriate ethical and regulatory procedures and has recently opened to requests for tissue and data.}, } @article {pmid26463840, year = {2016}, author = {Mäki-Nevala, S and Sarhadi, VK and Knuuttila, A and Scheinin, I and Ellonen, P and Lagström, S and Rönty, M and Kettunen, E and Husgafvel-Pursiainen, K and Wolff, H and Knuutila, S}, title = {Driver Gene and Novel Mutations in Asbestos-Exposed Lung Adenocarcinoma and Malignant Mesothelioma Detected by Exome Sequencing.}, journal = {Lung}, volume = {194}, number = {1}, pages = {125-135}, pmid = {26463840}, issn = {1432-1750}, mesh = {Adenocarcinoma/*genetics ; Asbestos/adverse effects ; Cell Adhesion Molecules/genetics ; Coatomer Protein/genetics ; DNA Mutational Analysis ; ErbB Receptors/genetics ; Exome/*genetics ; Female ; Humans ; Lung Neoplasms/*genetics ; Male ; Membrane Glycoproteins/genetics ; Mesothelioma/*genetics ; Mesothelioma, Malignant ; Mitochondrial Proteins/genetics ; Peptide Synthases/genetics ; Peritoneal Neoplasms/*genetics ; Phosphoric Monoester Hydrolases/genetics ; Pleural Neoplasms/*genetics ; Polymorphism, Single Nucleotide ; Proto-Oncogene Proteins B-raf/genetics ; Proto-Oncogene Proteins p21(ras)/genetics ; Receptors, Eph Family/genetics ; Ribosomal Proteins/genetics ; Semaphorins/genetics ; Tumor Suppressor Proteins/genetics ; Ubiquitin Thiolesterase/genetics ; }, abstract = {BACKGROUND: Asbestos is a carcinogen linked to malignant mesothelioma (MM) and lung cancer. Some gene aberrations related to asbestos exposure are recognized, but many associated mutations remain obscure. We performed exome sequencing to determine the association of previously known mutations (driver gene mutations) with asbestos and to identify novel mutations related to asbestos exposure in lung adenocarcinoma (LAC) and MM.

METHODS: Exome sequencing was performed on DNA from 47 tumor tissues of MM (21) and LAC (26) patients, 27 of whom had been asbestos-exposed (18 MM, 9 LAC). In addition, 9 normal lung/blood samples of LAC were sequenced. Novel mutations identified from exome data were validated by amplicon-based deep sequencing. Driver gene mutations in BRAF, EGFR, ERBB2, HRAS, KRAS, MET, NRAS, PIK3CA, STK11, and ephrin receptor genes (EPHA1-8, 10 and EPHB1-4, 6) were studied for both LAC and MM, and in BAP1, CUL1, CDKN2A, and NF2 for MM.

RESULTS: In asbestos-exposed MM patients, previously non-described NF2 frameshift mutation (one) and BAP1 mutations (four) were detected. Exome data mining revealed some genes potentially associated with asbestos exposure, such as MRPL1 and SDK1. BAP1 and COPG1 mutations were seen exclusively in MM. Pathogenic KRAS mutations were common in LAC patients (42 %), both in non-exposed (n = 5) and exposed patients (n = 6). Pathogenic BRAF mutations were found in two LACs.

CONCLUSION: BAP1 mutations occurred in asbestos-exposed MM. MRPL1, SDK1, SEMA5B, and INPP4A could possibly serve as candidate genes for alterations associated with asbestos exposure. KRAS mutations in LAC were not associated with asbestos exposure.}, } @article {pmid26448888, year = {2015}, author = {Desouki, MM and Long, DJ}, title = {Malignant Mesothelioma Mimicking Invasive Mammary Carcinoma in a Male Breast.}, journal = {Case reports in oncological medicine}, volume = {2015}, number = {}, pages = {298523}, pmid = {26448888}, issn = {2090-6706}, abstract = {Malignant mesothelioma is an uncommon tumor with strong association with asbestos exposure. Few cases of malignant pleural mesothelioma metastatic to the female breast have been reported. Herein, we presented, for the first time, a case of locally infiltrating malignant pleural mesothelioma forming a mass in the breast of a male as the first pathologically confirmed manifestation of the disease. Breast ultrasound revealed an irregular mass in the right breast which involves the pectoralis muscle. Breast core biopsy revealed a proliferation of neoplastic epithelioid cells mimicking an infiltrating pleomorphic lobular carcinoma. IHC studies showed the cells to be positive for calretinin, CK5/6, WT1, and CK7. The cells were negative for MOC-31, BerEp4, ER, and PR. A final diagnosis of malignant mesothelioma, epithelioid type, was rendered. This case demonstrates the importance of considering a broad differential diagnosis in the setting of atypical presentation with application of a panel of IHC markers.}, } @article {pmid26435024, year = {2015}, author = {Jankovichova, T and Jankovich, M and Ondrus, D and Kajo, K and Dubravicky, J and Breza, J}, title = {Extremely rare tumour--malignant mesothelioma of tunica vaginalis testis.}, journal = {Bratislavske lekarske listy}, volume = {116}, number = {9}, pages = {574-576}, doi = {10.4149/bll_2015_111}, pmid = {26435024}, issn = {0006-9248}, mesh = {Aged ; Asbestos/*adverse effects ; Humans ; Lung Neoplasms/etiology/*pathology ; Male ; Mesothelioma/etiology/*pathology ; Mesothelioma, Malignant ; Testicular Hydrocele/etiology/*pathology ; Testicular Neoplasms/etiology/*pathology ; }, abstract = {INTRODUCTION: Malignant mesothelioma of tunica vaginalis testis is an extremely rare tumour. It is often caused by exposition to asbestos, however, more often its occurrence is sporadic. The diagnosis is usually set secondarily during hydrocele surgery. This type of tumour should be considered in cases with with atypical hydrocele, especially haematocele or atypical shape of seminal covering.

RESULTS: A case of an asbestos-exposed patient with described disease and long-term hydrocele is presented. The number of patients is so small that the guidelines are limited due to low statistical power (Fig. 2, Ref. 14).}, } @article {pmid26433514, year = {2015}, author = {Marcq, E and Pauwels, P and van Meerbeeck, JP and Smits, EL}, title = {Targeting immune checkpoints: New opportunity for mesothelioma treatment?.}, journal = {Cancer treatment reviews}, volume = {41}, number = {10}, pages = {914-924}, doi = {10.1016/j.ctrv.2015.09.006}, pmid = {26433514}, issn = {1532-1967}, mesh = {Antigens, CD/immunology ; Antineoplastic Agents/*therapeutic use ; B7-H1 Antigen/antagonists & inhibitors/immunology ; CTLA-4 Antigen/*antagonists & inhibitors/immunology ; Hepatitis A Virus Cellular Receptor 2 ; Humans ; Immunologic Factors/*therapeutic use ; Lung Neoplasms/*drug therapy/immunology ; Membrane Proteins/antagonists & inhibitors/immunology ; Mesothelioma/*drug therapy/immunology ; Mesothelioma, Malignant ; Pleural Neoplasms/*drug therapy/immunology ; Programmed Cell Death 1 Ligand 2 Protein/antagonists & inhibitors/immunology ; Programmed Cell Death 1 Receptor/*antagonists & inhibitors/immunology ; Lymphocyte Activation Gene 3 Protein ; }, abstract = {Malignant pleural mesothelioma is an aggressive cancer linked to asbestos exposure in most patients. Due to the long latency between exposure and presentation, incidence is expected to further increase in the next decade, despite the ban on asbestos import which occurred at the end of last century in industrialized countries. Platinum-based palliative chemotherapy is the only treatment with proven benefit on outcome, resulting in selected patients in a median overall survival of about 1 year. Therefore, there is room for therapeutic improvement using a new strategy to prolong survival. Dealing with cancer cell induced immunosuppression is a promising approach. Reactivating immune responses that are silenced by immune checkpoints recently gained a lot of interest. Checkpoint blockade has already shown promising preclinical and clinical results in several cancer types and is currently also being investigated in mesothelioma. Here, we discuss the expression patterns and mechanisms of action of CTLA-4 and PD-1 as the two most studied and of TIM-3 and LAG-3 as two interesting upcoming immune checkpoints. Furthermore, we review the clinical results of molecules blocking these immune checkpoints and point out their future opportunities with a special focus on mesothelioma.}, } @article {pmid26433083, year = {2016}, author = {D'Antonio, A and Mastella, F and Colucci, A and Silvestre, G}, title = {Malignant Mesothelioma of Spermatic Cord in an Elderly Man With a History of Asbestos Exposure.}, journal = {Urology}, volume = {87}, number = {}, pages = {e1-3}, doi = {10.1016/j.urology.2015.09.020}, pmid = {26433083}, issn = {1527-9995}, mesh = {Aged, 80 and over ; Asbestos/*adverse effects ; Humans ; Lung Neoplasms/*chemically induced/diagnosis/surgery ; Male ; Mesothelioma/*chemically induced/diagnosis/surgery ; Mesothelioma, Malignant ; Occupational Exposure/*adverse effects ; Orchiectomy/*methods ; *Spermatic Cord ; Testicular Neoplasms/*chemically induced/diagnosis/surgery ; }, abstract = {We report a case of malignant mesothelioma of the spermatic cord in 80-year-old man presented with retained testis, hydrocele, and right inguinal mass. The patient had a long history of asbestos exposure as a railway worker. The patient was submitted to inguinal radical orchiectomy. One year after surgery, the patient is alive without signs of disease. Malignant mesothelioma of spermatic cord is a very rare disease, but this diagnosis should be suspected in patient with a history of asbestos exposure.}, } @article {pmid26431916, year = {2015}, author = {Santarelli, L and Staffolani, S and Strafella, E and Nocchi, L and Manzella, N and Grossi, P and Bracci, M and Pignotti, E and Alleva, R and Borghi, B and Pompili, C and Sabbatini, A and Rubini, C and Zuccatosta, L and Bichisecchi, E and Valentino, M and Horwood, K and Comar, M and Bovenzi, M and Dong, LF and Neuzil, J and Amati, M and Tomasetti, M}, title = {Combined circulating epigenetic markers to improve mesothelin performance in the diagnosis of malignant mesothelioma.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {90}, number = {3}, pages = {457-464}, doi = {10.1016/j.lungcan.2015.09.021}, pmid = {26431916}, issn = {1872-8332}, mesh = {Aged ; *Biomarkers, Tumor ; DNA Methylation ; *Epigenesis, Genetic ; Female ; GPI-Linked Proteins/blood/*genetics ; Humans ; Lung Neoplasms/blood/*diagnosis/etiology/*genetics/therapy ; Male ; Mesothelin ; Mesothelioma/blood/*diagnosis/etiology/*genetics/therapy ; Mesothelioma, Malignant ; MicroRNAs/blood/genetics ; Middle Aged ; Multidrug Resistance-Associated Proteins/blood ; Prognosis ; Reproducibility of Results ; }, abstract = {OBJECTIVES: Malignant mesothelioma (MM) is a highly aggressive tumor with poor prognosis. A major challenge is the development and application of early and highly reliable diagnostic marker(s). Serum biomarkers, such as 'soluble mesothelin-related proteins' (SMRPs), is the most studied and frequently used in MM. However, the low sensitivity of SMRPs for early MM limits its value; therefore, additional biomarkers are required. In this study, two epigenetically regulated markers in MM (microRNA-126, miR-126, and methylated thrombomodulin promoter, Met-TM) were combined with SMRPs and evaluated as a potential strategy to detect MM at an early stage.

MATERIALS AND METHODS: A total of 188 subjects, including 45 MM patients, 99 asbestos-exposed subjects, and 44 healthy controls were prospectively enrolled, serum samples collected, and serum levels of SMRPs, miR-126 and Met-TM evaluated. Logistic regression analysis was performed to evaluate the diagnostic value of the three biomarkers. Using this approach, the performance of the '3-biomarker classifier' was tested by calculating the overall probability score of the MM and control samples, respectively, and the ROC curve was generated.

RESULTS AND CONCLUSION: The combination of the three biomarkers was the best predictor to differentiate MM patients from asbestos-exposed subjects and healthy controls. The accuracy and cancer specificity was confirmed in a second validation cohort and lung cancer population. We propose that the combination of the two epigenetic biomarkers with SMRPs as a diagnosis for early MM overcomes the limitations of using SMRPs alone.}, } @article {pmid26421826, year = {2015}, author = {Francisci, S and Minicozzi, P and Pierannunzio, D and Ardanaz, E and Eberle, A and Grimsrud, TK and Knijn, A and Pastorino, U and Salmerón, D and Trama, A and Sant, M and , }, title = {Survival patterns in lung and pleural cancer in Europe 1999-2007: Results from the EUROCARE-5 study.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {51}, number = {15}, pages = {2242-2253}, doi = {10.1016/j.ejca.2015.07.033}, pmid = {26421826}, issn = {1879-0852}, abstract = {BACKGROUND: Survival of patients diagnosed with lung and pleura cancer is a relevant health care indicator which is related to the availability and access to early diagnosis and treatment facilities. Aim of this paper is to update lung and pleural cancer survival patterns and time trends in Europe using the EUROCARE-5 database.

METHODS: Data on adults diagnosed with lung and pleural cancer from 87 European cancer registries in 28 countries were analysed. Relative survival (RS) in 2000-2007 by country/region, age and gender, and over time trends in 1999-2007 were estimated.

RESULTS: Lung cancer survival is poor everywhere in Europe, with a RS of 39% and 13% at 1 and 5years since diagnosis, respectively. A geographical variability is present across European areas with a maximum regional difference of 12 and 5 percentage points in 1-year and 5-year RS respectively. Pleural cancer represents 4% of cases included in the present study with 7% 5-year RS overall in Europe. Most pleural cancers (83%) are microscopically verified mesotheliomas. Survival for both cancers decreases with advancing age at diagnosis for both cancers. Slight increasing trends are described for lung cancer. Survival over time is higher for squamous cell carcinoma and adenocarcinomas than for small and large cell carcinoma; and better among women than men.

CONCLUSIONS: Despite the generalised although slight increase, survival of lung and pleural cancer patients still remains poor in European countries. Priority should be given to prevention, with tobacco control policies across Europe for lung cancer and banning asbestos exposure for pleural cancer, and in early diagnosis and better treatment. The management of mesothelioma needs a multidisciplinary team and standardised health care strategies.}, } @article {pmid26418833, year = {2016}, author = {Peng, WJ and Mi, J and Jiang, YH}, title = {Asbestos exposure and laryngeal cancer mortality.}, journal = {The Laryngoscope}, volume = {126}, number = {5}, pages = {1169-1174}, doi = {10.1002/lary.25693}, pmid = {26418833}, issn = {1531-4995}, mesh = {Asbestos/*adverse effects ; Female ; Humans ; Laryngeal Neoplasms/chemically induced/*mortality ; Male ; Occupational Exposure/*adverse effects ; Risk Factors ; Sex Factors ; }, abstract = {OBJECTIVES/HYPOTHESIS: Occupational exposure to asbestos occurs in many workplaces and is well known to cause asbestosis, lung cancer, and mesothelioma. However, the link between asbestos exposure and other malignancies was not confirmed. The aim of the current meta-analysis was to provide a summary measure of risk for laryngeal cancer associated with occupational asbestos exposure.

STUDY DESIGN: Systematic review and meta-analysis.

METHODS: Electronic databases were searched for studies characterizing the association between asbestos and laryngeal cancer. Standardized mortality rate (SMR) with its 95% confidence interval (CI) of each study was combined using a fixed or random effect model.

RESULTS: Significantly increased SMR for laryngeal cancer was observed when subjects were exposed to asbestos (SMR = 1.69, 95% CI = 1.45-1.97, P < .001), with little evidence of heterogeneity among studies (Q = 15.39, P = .803, I(2) = 0.0%). Effect estimates were larger for cohorts controlling for male subjects, Europe and Oceania, mining and textile industries, exposure to crocidolite, long study follow-up (>25 years), and SMR for lung cancer > 2.0. Publication bias was not detect by Begg test (P = .910) and Egger test (P = .340).

CONCLUSIONS: Our study supports the association of exposure to asbestos with an increased risk of laryngeal cancer mortality among male workers.

LEVEL OF EVIDENCE: NA Laryngoscope, 126:1169-1174, 2016.}, } @article {pmid26409435, year = {2015}, author = {Cheung, M and Kadariya, Y and Talarchek, J and Pei, J and Ohar, JA and Kayaleh, OR and Testa, JR}, title = {Germline BAP1 mutation in a family with high incidence of multiple primary cancers and a potential gene-environment interaction.}, journal = {Cancer letters}, volume = {369}, number = {2}, pages = {261-265}, pmid = {26409435}, issn = {1872-7980}, support = {P30 CA006927/CA/NCI NIH HHS/United States ; P42 ES023720/ES/NIEHS NIH HHS/United States ; R01 CA175691/CA/NCI NIH HHS/United States ; P30 CA06927/CA/NCI NIH HHS/United States ; }, mesh = {Asbestos/*metabolism ; Disease Susceptibility ; Gene-Environment Interaction ; Germ-Line Mutation ; Humans ; Incidence ; Melanoma/*genetics/metabolism/pathology ; Neoplasms/*genetics/metabolism ; Skin Neoplasms ; Tumor Suppressor Proteins/*genetics/metabolism ; Ubiquitin Thiolesterase/*genetics/metabolism ; Melanoma, Cutaneous Malignant ; }, abstract = {We report a high-risk cancer family with multiple mesotheliomas, cutaneous melanomas, basal cell carcinomas, and meningiomas segregating with a germline nonsense mutation in BAP1 (c.1938T>A; p.Y646X). Notably, most (four of five) mesotheliomas were peritoneal rather than the usually more common pleural form of the disease, and all five mesothelioma patients also developed second or third primary cancers, including two with meningiomas. Another family member developed both cutaneous melanoma and breast cancer. Two family members had basal cell carcinomas, and six others had melanocytic tumors, including four cutaneous melanomas, one uveal melanoma, and one benign melanocytic tumor. The family resides in a subtropical area, and several members had suspected exposure to asbestos either occupationally or in the home. We hypothesize that the concurrence of a genetic predisposing factor and environmental exposure to asbestos and UV irradiation contributed to the high incidence of multiple cancers seen in this family, specifically mesothelioma and various uveal/skin tumors, respectively.}, } @article {pmid26398408, year = {2015}, author = {Baur, X}, title = {[Asbestos: Social Legal and Scientific Controversies and Unsound Science in the Context with the Worldwide Asbestos Tragedy - Lessions to be Learned].}, journal = {Pneumologie (Stuttgart, Germany)}, volume = {69}, number = {11}, pages = {654-661}, doi = {10.1055/s-0034-1393038}, pmid = {26398408}, issn = {1438-8790}, mesh = {*Asbestos ; Asbestosis/diagnosis/*epidemiology ; Evidence-Based Medicine/ethics/legislation & jurisprudence ; Expert Testimony/ethics/*legislation & jurisprudence ; Global Health/ethics/*legislation & jurisprudence ; Humans ; Lung Neoplasms/diagnosis/*epidemiology ; Prevalence ; Social Justice/ethics/*legislation & jurisprudence ; }, abstract = {8 to 15% of lung cancer cases and nearly all mesothelioma cases are caused by asbestos. Problems in compensation issues refer to high legal as well as insurance barriers in attesting the occupational diseases. Claiming of certain numbers of asbestos bodies or fibers in lung tissue is of special relevance in substantiating legal medical cases. Such evidence, which is disproved by a sound science, is also used by an influential US pathology department. Frequently, also epidemiological evidence with its causal relationships and exposure histories are ignored. Similar misleading arguments are currently found in industrializing countries where white asbestos which is carcinogenic and fibrogenic like other asbestos types, is efficiently promoted as less harm. As a result, the asbestos consumption is increasing in some of these countries. Beyond the worldwide asbestos tragedy a well-designed strategy of certain transnational or global acting industrial interest groups can be recognized. Their plan, hidden from the public eyes, follows rigorously sole economic interests, while leaving the resulting health harm to the public health systems.}, } @article {pmid26391798, year = {2015}, author = {Kramer, D and McMillan, K and Gross, E and Kone Pefoyo, AJ and Bradley, M and Holness, DL}, title = {From Awareness to Action: The Community of Sarnia Mobilizes to Protect its Workers from Occupational Disease.}, journal = {New solutions : a journal of environmental and occupational health policy : NS}, volume = {25}, number = {3}, pages = {377-410}, doi = {10.1177/1048291115604427}, pmid = {26391798}, issn = {1541-3772}, mesh = {*Awareness ; Canada ; Capacity Building/*organization & administration ; Communication ; Community-Institutional Relations ; *Cooperative Behavior ; Humans ; Interinstitutional Relations ; Leadership ; Lung Neoplasms/chemically induced ; Mesothelioma/chemically induced ; Neoplasms/*chemically induced/*prevention & control ; Occupational Exposure/*prevention & control ; Occupational Health ; Social Change ; }, abstract = {An exploratory qualitative case study investigated how different sectors of a highly industrialized community mobilized in the 1990s to help workers exposed to asbestos. For this study, thirty key informants including representatives from industry, workers, the community, and local politicians participated in semi-structured interviews and focus groups. The analysis was framed by a "Dimensions of Community Change" model. The informants highlighted the importance of raising awareness, and the need for leadership, social and organizational networks, acquiring skills and resources, individual and community power, holding shared values and beliefs, and perseverance. We found that improvements in occupational health and safety came from persistently communicating a clearly defined issue ("asbestos exposure causes cancer") and having an engaged community that collaborated with union leadership. Notable successes included stronger occupational health services, a support group for workers and widows, the fast-tracking of compensation for workers exposed to asbestos, and a reduction in hazardous emissions.}, } @article {pmid26386124, year = {2015}, author = {Nowak, AK and Cook, AM and McDonnell, AM and Millward, MJ and Creaney, J and Francis, RJ and Hasani, A and Segal, A and Musk, AW and Turlach, BA and McCoy, MJ and Robinson, BW and Lake, RA}, title = {A phase 1b clinical trial of the CD40-activating antibody CP-870,893 in combination with cisplatin and pemetrexed in malignant pleural mesothelioma.}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {26}, number = {12}, pages = {2483-2490}, doi = {10.1093/annonc/mdv387}, pmid = {26386124}, issn = {1569-8041}, mesh = {Adult ; Aged ; Antibodies, Monoclonal/*administration & dosage ; Antibodies, Monoclonal, Humanized ; Antineoplastic Combined Chemotherapy Protocols/*administration & dosage ; CD40 Antigens/agonists/*metabolism ; Cisplatin/*administration & dosage ; Cohort Studies ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/diagnosis/*drug therapy/metabolism ; Male ; Mesothelioma/diagnosis/*drug therapy/metabolism ; Mesothelioma, Malignant ; Middle Aged ; Pemetrexed/*administration & dosage ; Pleural Neoplasms/diagnosis/*drug therapy/metabolism ; Prospective Studies ; }, abstract = {BACKGROUND: Data from murine models suggest that CD40 activation may synergize with cytotoxic chemotherapy. We aimed to determine the maximum tolerated dose (MTD) and toxicity profile and to explore immunological biomarkers of the CD40-activating antibody CP-870,893 with cisplatin and pemetrexed in patients with malignant pleural mesothelioma (MPM).

PATIENTS AND METHODS: Eligible patients had confirmed MPM, ECOG performance status 0-1, and measurable disease. Patients received cisplatin 75 mg/m(2) and pemetrexed 500 mg/m(2) on day 1 and CP-870,893 on day 8 of a 21-day cycle for maximum 6 cycles with up to 6 subsequent cycles single-agent CP-870,893. Immune cell subset changes were examined weekly by flow cytometry.

RESULTS: Fifteen patients were treated at three dose levels. The MTD of CP-870,893 was 0.15 mg/kg, and was exceeded at 0.2 mg/kg with one grade 4 splenic infarction and one grade 3 confusion and hyponatraemia. Cytokine release syndrome (CRS) occurred in most patients (80%) following CP-870,893. Haematological toxicities were consistent with cisplatin and pemetrexed chemotherapy. Six partial responses (40%) and 9 stable disease (53%) as best response were observed. The median overall survival was 16.5 months; the median progression-free survival was 6.3 months. Three patients survived beyond 30 months. CD19+ B cells decreased over 6 cycles of chemoimmunotherapy (P < 0.001) with a concomitant increase in the proportion of CD27+ memory B cells (P < 0.001) and activated CD86+CD27+ memory B cells (P < 0.001), as an immunopharmacodynamic marker of CD40 activation.

CONCLUSIONS: CP-870,893 with cisplatin and pemetrexed is safe and tolerable at 0.15 mg/kg, although most patients experience CRS. While objective response rates are similar to chemotherapy alone, three patients achieved long-term survival.

ACTRN12609000294257.}, } @article {pmid26384258, year = {2015}, author = {Magnani, C and Bianchi, C and Chellini, E and Consonni, D and Fubini, B and Gennaro, V and Marinaccio, A and Menegozzo, M and Mirabelli, D and Merler, E and Merletti, F and Musti, M and Oddone, E and Romanelli, A and Terracini, B and Zona, A and Zocchetti, C and Alessi, M and Baldassarre, A and Dianzani, I and Maule, M and Mensi, C and Silvestri, S}, title = {III Italian Consensus Conference on Malignant Mesothelioma of the Pleura. Epidemiology, Public Health and Occupational Medicine related issues.}, journal = {La Medicina del lavoro}, volume = {106}, number = {5}, pages = {325-332}, pmid = {26384258}, issn = {0025-7818}, mesh = {Asbestos/adverse effects ; Humans ; Italy ; *Lung Neoplasms/epidemiology/etiology ; *Mesothelioma/epidemiology/etiology ; Mesothelioma, Malignant ; *Occupational Diseases/epidemiology/etiology ; Occupational Medicine ; *Pleural Neoplasms/epidemiology/etiology ; Public Health ; }, abstract = {The III Italian Consensus Conference on Pleural Mesothelioma (MM) convened on January 29th 2015. This report presents the conclusions of the 'Epidemiology, Public Health and Occupational Medicine' section. MM incidence in 2011 in Italy was 3.64 per 100,000 person/years in men and 1.32 in women. Incidence trends are starting to level off. Ten percent of cases are due to non-occupational exposure. Incidence among women is very high in Italy, because of both non-occupational and occupational exposure. The removal of asbestos in place is proceeding slowly, with remaining exposure. Recent literature confirms the causal role of chrysotile. Fibrous fluoro-edenite was classified as carcinogenic by IARC (Group 1) on the basis of MM data. A specific type (MWCNT-7) of Carbon Nanotubes was classified 2B. For pleural MM, after about 45 years since first exposure, the incidence trend slowed down; with more studies needed. Cumulative exposure is a proxy of the relevant exposure, but does not allow to distinguish if duration or intensity may possibly play a prominent role, neither to evaluate the temporal sequence of exposures. Studies showed that duration and intensity are independent determinants of MM. Blood related MM are less than 2.5%. The role of BAP1 germline mutations is limited to the BAP1 cancer syndrome, but negligible for sporadic cases. Correct MM diagnosis is baseline; guidelines agree on the importance of the tumor gross appearance and of the hematoxylin-eosin-based histology. Immunohistochemical markers contribute to diagnostic confirmation: the selection depends on morphology, location, and differential diagnosis. The WG suggested that 1) General Cancer Registries and ReNaM Regional Operational Centres (COR) interact and systematically compare MM cases; 2) ReNaM should report results presenting the diagnostic certainty codes and the diagnostic basis, separately; 3) General Cancer Registries and COR should interact with pathologists to assure the up-to-date methodology; 4) Necroscopy should be practiced for validation. Expert referral centres could contribute to the definition of uncertain cases. Health surveillance should aim to all asbestos effects. No diagnostic test is recommended for MM screening. Health surveillance should provide information on risks, medical perspective, and smoking cessation. The economic burden associated to MM was estimated in 250,000 Euro per case.}, } @article {pmid26377289, year = {2015}, author = {Musk, AW and Olsen, N and Alfonso, H and Peters, S and Franklin, P}, title = {Pattern of malignant mesothelioma incidence and occupational exposure to asbestos in Western Australia.}, journal = {The Medical journal of Australia}, volume = {203}, number = {6}, pages = {251-2e.1}, doi = {10.5694/mja15.00337}, pmid = {26377289}, issn = {1326-5377}, mesh = {Asbestos/*poisoning ; Humans ; Lung Neoplasms/*epidemiology ; Mesothelioma/*epidemiology ; Mesothelioma, Malignant ; *Occupational Exposure ; Western Australia/epidemiology ; }, } @article {pmid26376726, year = {2015}, author = {Isoda, R and Yamane, H and Nezuo, S and Monobe, Y and Ochi, N and Honda, Y and Nishimura, S and Akiyama, M and Horio, T and Takigawa, N}, title = {Successful palliation for an aged patient with primary pericardial mesothelioma.}, journal = {World journal of surgical oncology}, volume = {13}, number = {}, pages = {273}, pmid = {26376726}, issn = {1477-7819}, mesh = {Aged, 80 and over ; Asbestos/*adverse effects ; Carcinogens/pharmacology ; Cardiac Tamponade/etiology/pathology/*therapy ; Heart Neoplasms/*complications/pathology ; Humans ; Male ; Mesothelioma/*complications/pathology ; *Palliative Care ; Pericardial Effusion/etiology/pathology/*therapy ; Pericardiocentesis ; Pleural Neoplasms/*complications/pathology ; Prognosis ; }, abstract = {An 85-year-old Japanese man with a complaint of exertional dyspnea was admitted to our hospital. Sixty-three years prior to admission at our hospital, he handled asbestos for 2 years in a factory. His chest computed tomography showed a massive pericardial effusion leading to cardiac tamponade and right pleural plaque. After a pericardiocentesis was performed, he recovered from cardiac failure caused by the cardiac tamponade. Pathological examination of the pericardial effusion revealed malignant mesothelial cells. Therefore, he was diagnosed with primary pericardial mesothelioma (PPM) related to asbestos exposure. Although his disease slowly progressed over 18 months, he remained active without any adjuvant treatments such as chemotherapy. Long-term palliation in an aged patient with PPM is rarely obtained using supportive care alone because the prognosis of PPM has been consistently reported to be very poor and almost fatal within a year. Clinical oncologists and thoracic surgeons should be aware of this disease because the accumulation of knowledge on PPM may lead to successful treatment even in aged patients.}, } @article {pmid26376466, year = {2015}, author = {Tsukamoto, Y and Otsuki, T and Hao, H and Kuribayashi, K and Nakano, T and Kida, A and Nakanishi, T and Funatsu, E and Noguchi, C and Yoshihara, S and Kaku, K and Hirota, S}, title = {Epithelioid pleural mesothelioma concurrently associated with miliary pulmonary metastases and minimal change nephrotic syndrome - A hitherto undescribed case.}, journal = {Pathology, research and practice}, volume = {211}, number = {12}, pages = {1014-1019}, doi = {10.1016/j.prp.2015.07.013}, pmid = {26376466}, issn = {1618-0631}, mesh = {Aged ; Fatal Outcome ; Humans ; Lung Neoplasms/complications/*secondary ; Male ; Mesothelioma/complications/*secondary ; Mesothelioma, Malignant ; Nephrosis, Lipoid/*complications ; Pleural Neoplasms/complications/*pathology ; }, abstract = {Malignant pleural mesothelioma (MPM) is the aggressive disease typically spreading along the pleural surface and encasing the lung, leading to respiratory failure or cachexia. Rare cases with atypical clinical manifestation or presentation have been reported in MPM. We experienced a unique case of MPM concurrently associated with miliary pulmonary metastases and nephrotic syndrome. A 73-year-old Japanese man with past history of asbestos exposure was referred to our hospital for the investigation of the left pleural effusion. Chest computed tomography showed thickening of the left parietal pleura. Biopsy specimen of the pleura showed proliferating epithelioid tumor cells, leading to the pathological diagnosis of epithelioid MPM with the aid of immunohistochemistry. After the diagnosis of MPM, chemotherapy was performed without effect. Soon after the clinical diagnosis of progressive disease with skull metastasis, edema and weight gain appeared. Laboratory data met the criteria of nephrotic syndrome, and renal biopsy with electron microscopic examination revealed the minimal change disease. Steroid therapy was started but showed no effect. Around the same time of onset of nephrotic syndrome, multiple miliary lung nodules appeared on chest CT. Transbronchial biopsy specimen of the nodules showed the metastatic MPM in the lung. The patient died because of the worsening of the general condition. To our knowledge, this is the first case of MPM concurrently associated with multiple miliary pulmonary metastases and nephrotic syndrome.}, } @article {pmid26371785, year = {2015}, author = {Pavlisko, EN and Roggli, VL}, title = {Sarcomatoid Peritoneal Mesothelioma: Clinicopathologic Correlation of 13 Cases.}, journal = {The American journal of surgical pathology}, volume = {39}, number = {11}, pages = {1568-1575}, doi = {10.1097/PAS.0000000000000495}, pmid = {26371785}, issn = {1532-0979}, mesh = {Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Autopsy ; Biomarkers, Tumor/analysis ; Biopsy ; Databases, Factual ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; Incidence ; Inhalation Exposure/adverse effects ; Keratins/analysis ; Lung Neoplasms/chemistry/mortality/*pathology ; Male ; Mesothelioma/chemistry/mortality/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/adverse effects ; Peritoneal Neoplasms/chemistry/mortality/*pathology ; Predictive Value of Tests ; Prognosis ; Risk Factors ; Sarcoma/chemistry/mortality/*pathology ; Survival Analysis ; }, abstract = {Peritoneal mesothelioma is rare, and the sarcomatoid variant is more infrequent, with <30 cases reported to date in the literature. Several case series have described the morphologic features of sarcomatoid peritoneal mesothelioma (SPe); however, the clinicopathologic features are not well characterized. To our knowledge, this is the first large series reporting the clinicopathologic features of SPe. We reviewed our database of 3106 malignant mesothelioma cases. Of 248 peritoneal mesotheliomas, 15 (4%) were sarcomatoid variant (0.5% of all mesotheliomas). Only cases with 100% sarcomatoid morphology diagnosed by open surgical biopsy and/or autopsy were included. Thus, 4 cases were excluded leaving 11 cases of SPe. Two additional cases of SPe previously published by 1 of the authors (V.L.R.), not included in the database, are added yielding 13 cases total. The median age at diagnosis was 66 years (range=48 to 85 y), and there was a male predominance (M:F=3.25:1). Survival from date of diagnosis to date of death was 5 months (range=0 to 12 mo). The most common presenting symptom was abdominal pain, and 3 of 4 women were suspected to have cholecystitis/cholelithiasis. All cases stained positive for cytokeratins, and 2 contained heterologous elements. Seven cases had objective markers of asbestos exposure, and 2 additional cases had occupations strongly associated with mesothelioma. Two cases with alleged household contact exposures could not be confirmed to be asbestos related by lung fiber analysis. SPe is a rare variant of mesothelioma attributed to asbestos exposure in 69% of our cases.}, } @article {pmid26366399, year = {2015}, author = {Zhang, W and Wu, X and Wu, L and Zhang, W and Zhao, X}, title = {Advances in the diagnosis, treatment and prognosis of malignant pleural mesothelioma.}, journal = {Annals of translational medicine}, volume = {3}, number = {13}, pages = {182}, pmid = {26366399}, issn = {2305-5839}, abstract = {Malignant pleural mesothelioma (MPM) is a rare cancer originated from pleural mesothelial cells. MPM has been associated with long-term exposure to asbestos. The prognosis of MPM is poor due to the difficulty of making diagnosis in the early stage, the rapid progression, the high invasiveness and the lack of effective treatment. Although the incidence of MPM is low in China to date, it has a tendency to increase in the coming years. The variety of clinical features may cause the delay of diagnosis and high rate of misdiagnosis. The diagnosis of MPM is based on biopsy of the pleura and immunohistochemistry. As China has become the largest country in the consumption of asbestos, it would give rise to a new surge of MPM in the future. The current treatment of MPM is multimodality therapy including surgery, radiotherapy, chemotherapy and immunotherapy. Two surgical procedures are commonly applied: extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D). Three dimensional conformal radiotherapy is used to denote a spectrum of radiation planning and delivery techniques that rely on the 3D imaging to define the tumor. Cisplatin combined with pemetrexed (PEM) is the first-line chemotherapy for MPM. The principal targets in immunotherapy include T cells (Treg), CTLA-4 and PD-1. The diagnosis, treatment and prognosis still remain a major challenge for clinical research and will do so for years to come.}, } @article {pmid26364960, year = {2017}, author = {Sim, JK and Oh, JY and Min, KH and Hur, GY and Shim, JJ and Kang, KH and Lee, SY}, title = {Malignant mesothelioma with fungating masses and multiple sites involvement.}, journal = {The clinical respiratory journal}, volume = {11}, number = {4}, pages = {524-528}, doi = {10.1111/crj.12383}, pmid = {26364960}, issn = {1752-699X}, mesh = {Asbestos/*adverse effects ; Drug Therapy/methods ; Dyspnea/*diagnosis/etiology ; Fatal Outcome ; Humans ; Lung Neoplasms/diagnostic imaging/drug therapy/*pathology ; Male ; Mesothelioma/diagnostic imaging/drug therapy/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Neoplasm Metastasis/pathology ; Pleura/cytology/*pathology/ultrastructure ; Pleural Effusion, Malignant/*diagnostic imaging ; Pleural Neoplasms/*pathology ; Positron-Emission Tomography ; Radiography ; Tomography, X-Ray Computed ; }, abstract = {Malignant mesothelioma (MM) is a rare tumor associated with asbestos exposure. It typically presents as thickening or nodularity of the pleura, although it can also originate from other sites consisting of mesothelia and have manifestations other than thickening or nodularity. Several studies have implied that these different manifestations are associated with a different tumor biology. We report the case of a 54-year-old man with multiple fungating masses diagnosed as MM on histological examination.}, } @article {pmid26364129, year = {2015}, author = {Cheung, M and Kadariya, Y and Pei, J and Talarchek, J and Facciolo, F and Visca, P and Righi, L and Cozzi, I and Testa, JR and Ascoli, V}, title = {An asbestos-exposed family with multiple cases of pleural malignant mesothelioma without inheritance of a predisposing BAP1 mutation.}, journal = {Cancer genetics}, volume = {208}, number = {10}, pages = {502-507}, pmid = {26364129}, issn = {2210-7762}, support = {P30 CA06927/CA/NCI NIH HHS/United States ; R01 CA175691/CA/NCI NIH HHS/United States ; CA175691/CA/NCI NIH HHS/United States ; P30 ES013508/ES/NIEHS NIH HHS/United States ; P42 ES023720/ES/NIEHS NIH HHS/United States ; P30 CA006927/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Female ; Genetic Predisposition to Disease ; Humans ; Lung Neoplasms/*chemically induced/*genetics ; Male ; Mesothelioma/*chemically induced/*genetics ; Mesothelioma, Malignant ; Middle Aged ; *Mutation ; Oligonucleotide Array Sequence Analysis ; Pedigree ; Pleural Neoplasms/*chemically induced/*genetics ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {We report a family with domestic exposure to asbestos and diagnosis of multiple cancers, including eight pleural malignant mesotheliomas and several other lung or pleural tumors. DNA sequence analysis revealed no evidence for an inherited mutation of BAP1. Sequence analysis of other potentially relevant genes, including TP53, CDKN2A, and BARD1, also revealed no mutation. DNA microarray analysis of tissue from two mesotheliomas revealed multiple genomic imbalances, including consistent losses of overlapping segments in 2q, 6q, 9p, 14q, 15q, and 22q, but no losses of chromosome 3 harboring the BAP1 locus. However, the results of immunohistochemical analysis demonstrated loss of nuclear BAP1 staining in three of six mesotheliomas tested, suggesting that somatic alterations of BAP1 occurred in a subset of tumors from this family. Since mesothelioma could be confirmed in only a single generation, domestic exposure to asbestos may be the predominant cause of mesothelioma in this family. Given the existence of unspecified malignant pleural tumors and lung cancers in a prior generation, we discuss the possibility that some other tumor susceptibility or modifier gene(s) may contribute to the high incidence of mesothelioma in this family. Because the incidence of mesothelioma in this family is higher than that expected even in workers heavily exposed to asbestos, we conclude that both asbestos exposure and genetic factors have played a role in the high rate of mesothelioma and potentially other pleural or lung cancers seen in this family.}, } @article {pmid26361957, year = {2015}, author = {Liu, H and Wu, L and Ji, K and Wang, W}, title = {Prognostic value of several biomarkers for the patients with malignant pleural mesothelioma.}, journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine}, volume = {36}, number = {10}, pages = {7375-7384}, pmid = {26361957}, issn = {1423-0380}, mesh = {Biomarkers, Tumor/*analysis ; Combined Modality Therapy ; Humans ; Lung Neoplasms/*diagnosis/metabolism/mortality/therapy ; Mesothelioma/*diagnosis/metabolism/mortality/therapy ; Mesothelioma, Malignant ; Pleural Neoplasms/*diagnosis/metabolism/mortality/therapy ; Prognosis ; Survival Rate ; }, abstract = {Malignant pleural mesothelioma (MPM) is a highly aggressive tumor of the pleura closely related to asbestos exposure. Rare as it is, the incidence of MPM is predicted to increase mainly as a result of a lengthy latency period from the initial asbestos exposure, making it a public health concern for the next decades. Moreover, the patients with MPM have an extremely poor prognosis due to its high resistance to conventional oncologic treatments and delayed diagnosis. Although the result of current therapeutic modalities based on patient features and clinical stages is very frustrating, great advances have been shown in the knowledge of molecular biology of MPM in recent years. This is accompanied by dozens of putative prognostic biomarkers that are actively involved in tumor biological activities. These prognostic candidates can offer us a new insight into the biological characteristics of MPM, contributing to development of individualized therapeutic strategies directed against oncogenesis and tumor progression. Thus, personalized approaches based on the molecular biology of the patient's tissue or body fluid will potentially improve the present disappointing outcome, bringing new hope for patients with MPM. This article reviews the principal and several novel biomarkers that can have an influence on prognosis, in the hope that they can provide us with a more profound understanding of the biology of this lethal disease.}, } @article {pmid26358421, year = {2016}, author = {Urso, L and Calabrese, F and Favaretto, A and Conte, P and Pasello, G}, title = {Critical review about MDM2 in cancer: Possible role in malignant mesothelioma and implications for treatment.}, journal = {Critical reviews in oncology/hematology}, volume = {97}, number = {}, pages = {220-230}, doi = {10.1016/j.critrevonc.2015.08.019}, pmid = {26358421}, issn = {1879-0461}, mesh = {Animals ; Humans ; *Lung Neoplasms ; *Mesothelioma ; Mesothelioma, Malignant ; Mice ; *Proto-Oncogene Proteins c-mdm2 ; Tumor Suppressor Protein p53/genetics ; }, abstract = {The tumor suppressor p53 regulates genes involved in DNA repair, metabolism, cell cycle arrest, apoptosis and senescence. p53 is mutated in about 50% of the human cancers, while in tumors with wild-type p53 gene, the protein function may be lost because of overexpression of Murine Double Minute 2 (MDM2). MDM2 targets p53 for ubiquitylation and proteasomal degradation. p53 reactivation through MDM2 inhibitors seems to be a promising strategy to sensitize p53 wild-type cancer cells to apoptosis. Moreover, additional p53-independent molecular functions of MDM2, such as neoangiogenesis promotion, have been suggested. Thus, MDM2 might be a target for anticancer treatment because of its antiapoptotic and proangiogenetic role. Malignant pleural mesothelioma (MPM) is an aggressive asbestos-related tumor where wild-type p53 might be present. The present review gives a complete landscape about the role of MDM2 in cancer pathogenesis, prognosis and treatment, with particular focus on Malignant Pleural Mesothelioma.}, } @article {pmid26351019, year = {2015}, author = {Conti, S and Minelli, G and Ascoli, V and Marinaccio, A and Bonafede, M and Manno, V and Crialesi, R and Straif, K}, title = {Peritoneal mesothelioma in Italy: Trends and geography of mortality and incidence.}, journal = {American journal of industrial medicine}, volume = {58}, number = {10}, pages = {1050-1058}, doi = {10.1002/ajim.22491}, pmid = {26351019}, issn = {1097-0274}, support = {001/WHO_/World Health Organization/International ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Databases, Factual ; Female ; Humans ; Incidence ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Occupational Diseases/*epidemiology ; Peritoneal Neoplasms/*epidemiology ; Registries ; Young Adult ; }, abstract = {INTRODUCTION: Peritoneal mesothelioma, a very rare and lethal malignancy, has not been investigated as extensively as pleural mesothelioma, although the role of asbestos exposure in its occurrence is well-known. Data from Italy are relevant, as it was the largest European asbestos producer, and asbestos was widely used in many economic activities.

METHODS: A population-based mortality and incidence analysis was performed in Italy. Data sources were the National Multiple-causes-of-death Database (1995-2010) and the Italian Mesothelioma Register (1993-2008).

RESULTS: We found an increasing trend of age standardized mortality rates in men, but no clear trend in women; moreover, we showed significant risks of death in several northern regions, formerly heavy asbestos users; finally, mortality/incidence ratios similar for both genders (about 0.8) were estimated.

CONCLUSIONS: The study, based on national data, showed a higher risk of mortality from and incidence of peritoneal mesothelioma in areas with formerly heavy exposure to asbestos.}, } @article {pmid26320384, year = {2015}, author = {Algranti, E and Saito, CA and Carneiro, AP and Moreira, B and Mendonça, EM and Bussacos, MA}, title = {The next mesothelioma wave: mortality trends and forecast to 2030 in Brazil.}, journal = {Cancer epidemiology}, volume = {39}, number = {5}, pages = {687-692}, doi = {10.1016/j.canep.2015.08.007}, pmid = {26320384}, issn = {1877-783X}, mesh = {Adult ; Asbestos/adverse effects ; Brazil/epidemiology ; *Developing Countries ; Female ; Forecasting ; Humans ; Incidence ; Industrial Development/trends ; Male ; Medical Oncology/*trends ; Mesothelioma/*mortality ; Middle Aged ; Pleural Neoplasms/*mortality ; }, abstract = {BACKGROUND: There are limited data on mesothelioma mortality in industrializing countries, where, at present, most of the asbestos consumption occurs.

OBJECTIVES: To analyze temporal trends and to calculate mortality rates from mesothelioma and cancer of the pleura in Brazil from 2000 to 2012 and to estimate future mortality rates.

METHODS: We retrieved records of deaths from mesothelioma (ICD-10C45) and cancer of the pleura (ICD-10C38.4) from 2000 to 2012 in adults aged 30 years and over. Crude and age-standardized mortality rates (ASMR) were calculated. Rate ratios of mean crude mortality for selected municipalities were compared to the Brazilian rate. A regression was carried out of the annual number of deaths against asbestos consumption using a Generalized Additive Model (GAM). The best model was chosen to estimate the future burden and peak period of deaths.

RESULTS: There were 929C45 and 1379 C38.4 deaths. The ratio of men to women for C45 was 1.4. A positive trend in C45 numbers was observed in Brazil (p=0.0012), particularly in São Paulo (p=0.0004) where ASMRs presented an increasing linear trend (p=0.0344). Selected municipalities harboring asbestos manipulation presented 3.7-11 fold rate ratios of C45 compared to Brazil. GAM presented best fits for latencies of 34 years or more. It is estimated that the peak incidence of C45 mortality will occur between 2021 and 2026.

CONCLUSIONS: The observed ASMRs and the gender ratio close to 1 suggest underreporting. Even so, deaths are increasing and mesothelioma clusters were identified. Compared to industrialized countries Brazil displays a 15-20 year lag in estimated peak mesothelioma mortality which is consistent with the lag of asbestos peak consumption in the country.}, } @article {pmid26318158, year = {2016}, author = {Garabrant, DH and Alexander, DD and Miller, PE and Fryzek, JP and Boffetta, P and Teta, MJ and Hessel, PA and Craven, VA and Kelsh, MA and Goodman, M}, title = {Mesothelioma among Motor Vehicle Mechanics: An Updated Review and Meta-analysis.}, journal = {The Annals of occupational hygiene}, volume = {60}, number = {1}, pages = {8-26}, doi = {10.1093/annhyg/mev060}, pmid = {26318158}, issn = {1475-3162}, mesh = {Asbestos/adverse effects ; Humans ; Lung Neoplasms/epidemiology/etiology ; Mesothelioma/*epidemiology ; *Motor Vehicles ; Occupational Diseases/*epidemiology/etiology ; Occupational Exposure/*adverse effects ; Risk Assessment ; }, abstract = {BACKGROUND: We published a meta-analysis of the association between work as a motor vehicle mechanic and mesothelioma in 2004. Since then, several relevant studies on this topic have been published. Thus, to update the state-of-the-science on this issue, we conducted a new systematic review and meta-analysis.

METHODS: A comprehensive PubMed literature search through May 2014 was conducted to identify studies that reported relative risk estimates for mesothelioma among motor vehicle mechanics (in general), and those who were engaged in brake repair (specifically). Studies were scored and classified based on study characteristics. Random-effects meta-analyses generated summary relative risk estimates (SRREs) and corresponding 95% confidence intervals (CI). Heterogeneity of results was examined by calculating Q-test P-values (P-H) and I (2) estimates. Sub-group and sensitivity analyses were conducted for relevant study characteristics and quality measures.

RESULTS: Ten case-control studies, one cohort study, and five proportionate mortality ratio (PMR)/standardized mortality odds ratio (SMOR) studies were identified and included in the quantitative assessment. Most meta-analysis models produced SRREs below 1.0, and no statistically significant increases in mesothelioma were observed. The SRRE for all studies was 0.80 (95% CI: 0.61-1.05) with significant heterogeneity (P-H <0.001, I (2) = 62.90). A similar SRRE was observed among the five Tier 1 studies with the highest quality ratings (SRRE = 0.76, 95% CI: 0.46-1.25), with no heterogeneity among studies (P-H = 0.912, I (2) = 0.00). Meta-analysis of the Tier 2 (n = 5) and Tier 3 (n = 6) studies resulted in SRREs of 1.09 (95% CI: 0.76-1.58) and 0.73 (95% CI: 0.49-1.08), respectively. Restricting the analysis to Tiers 1 and 2 combined resulted in an SRRE of 0.92 (95% CI: 0.72-1.29). The SRRE specific to brake work (n = 4) was 0.64 (95% CI: 0.38-1.09).

CONCLUSIONS: This meta-analysis of the epidemiologic studies provides evidence that motor vehicle mechanics, including workers who were engaged in brake repair, are not at an increased risk of mesothelioma.}, } @article {pmid26316950, year = {2015}, author = {Saint-Pierre, MD and Pease, C and Mithoowani, H and Zhang, T and Nicholas, GA and Laurie, SA and Wheatley-Price, P}, title = {Malignant Pleural Mesothelioma Outcomes in the Era of Combined Platinum and Folate Antimetabolite Chemotherapy.}, journal = {Lung cancer international}, volume = {2015}, number = {}, pages = {590148}, pmid = {26316950}, issn = {2090-3197}, abstract = {Introduction. Malignant pleural mesothelioma (MPM) is associated with a poor prognosis. Palliative platinum-based chemotherapy may help to improve symptoms and prolong life. Since 2004, the platinum is commonly partnered with a folate antimetabolite. We performed a review investigating if survival had significantly changed before and after the arrival of folate antimetabolites in clinical practice. Methods. All MPM patients from January 1991 to June 2012 were identified. Data collected included age, gender, asbestos exposure, presenting signs/symptoms, performance status, histology, stage, bloodwork, treatment modalities including chemotherapy, and date of death or last follow-up. The primary endpoint was overall survival. Cox models were applied to determine variables associated with survival. Results. There were 245 patients identified. Median overall survival for all patients was 9.4 months. After multivariate analysis, performance status, stage, histology, leucocytosis, and thrombophilia remained independently associated with survival. Among all patients who received chemotherapy, there was no difference in overall survival between the periods before and after folate antimetabolite approval: 14.2 versus 13.2 months (P = 0.35). Specifically receiving combined platinum-based/folate antimetabolite chemotherapy did not improve overall survival compared to all other chemotherapy regimens: 14.1 versus 13.6 months (P = 0.97). Conclusions. In this review, we did not observe an incremental improvement in overall survival after folate antimetabolites became available.}, } @article {pmid26310516, year = {2015}, author = {Imai, M and Hino, O}, title = {Environmental carcinogenesis - 100th anniversary of creating cancer.}, journal = {Cancer science}, volume = {106}, number = {11}, pages = {1483-1485}, pmid = {26310516}, issn = {1349-7006}, mesh = {Anniversaries and Special Events ; Environmental Exposure/*adverse effects/*history ; History, 20th Century ; History, 21st Century ; Humans ; Neoplasms/*etiology/*history ; }, abstract = {Asbestos is an environmental carcinogen, and asbestos-related diseases represent a global-scale environmental issue. Mesothelioma is an aggressive, malignant tumor that initially progresses along the surfaces of the pleura and peritoneum that is chiefly attributed to asbestos exposure. X-rays are commonly used for tumor screening in populations at risk for developing this cancer. We previously reported that the N-terminal of mesothelin may be a useful blood marker for early diagnosis method for mesothelioma and since then developed an N-terminal of mesothelin ELISA kit in collaboration with IBL Co., Ltd. and confirmed its utility as a diagnostic system for mesothelioma. Recently, we performed a large-scale research screening for mesothelioma and showed that it is a good model for early diagnosis in at-risk populations. The year 2015 is the 100th anniversary of Yamagiwa's great work on coaltar-induced carcinogenesis by formative stimulation in 1915 and the 10th year since 2005, "Kubota shock", people recognized that asbestos induces mesothelioma. We dedicate this review to this memorial year for environmental carcinogenesis.}, } @article {pmid26308799, year = {2015}, author = {Bononi, A and Napolitano, A and Pass, HI and Yang, H and Carbone, M}, title = {Latest developments in our understanding of the pathogenesis of mesothelioma and the design of targeted therapies.}, journal = {Expert review of respiratory medicine}, volume = {9}, number = {5}, pages = {633-654}, pmid = {26308799}, issn = {1747-6356}, support = {R01 CA198138/CA/NCI NIH HHS/United States ; CA120355/CA/NCI NIH HHS/United States ; P01 CA114047/CA/NCI NIH HHS/United States ; R01 CA160715/CA/NCI NIH HHS/United States ; R01 CA106567/CA/NCI NIH HHS/United States ; R01 CA160715-0A/CA/NCI NIH HHS/United States ; 1R01 CA198138-01/CA/NCI NIH HHS/United States ; P30 CA071789/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Immunotherapy/methods ; Lung Neoplasms/etiology/*genetics/physiopathology/*therapy ; Mesothelioma/etiology/*genetics/physiopathology/*therapy ; Mesothelioma, Malignant ; *Molecular Targeted Therapy/methods ; Peritoneal Neoplasms/etiology/genetics/physiopathology/therapy ; Pleural Neoplasms/etiology/*genetics/physiopathology/*therapy ; }, abstract = {Malignant mesothelioma is an aggressive cancer whose pathogenesis is causally linked to occupational exposure to asbestos. Familial clusters of mesotheliomas have been observed in settings of genetic predisposition. Mesothelioma incidence is anticipated to increase worldwide in the next two decades. Novel treatments are needed, as current treatment modalities may improve the quality of life, but have shown modest effects in improving overall survival. Increasing knowledge on the molecular characteristics of mesothelioma has led to the development of novel potential therapeutic strategies, including: molecular targeted approaches, that is the inhibition of vascular endothelial growth factor with bevacizumab; immunotherapy with chimeric monoclonal antibody, immunotoxin, antibody drug conjugate, vaccine and viruses; inhibition of asbestos-induced inflammation, that is aspirin inhibition of HMGB1 activity may decrease or delay mesothelioma onset and/or growth. We elaborate on the rationale behind new therapeutic strategies, and summarize available preclinical and clinical results, as well as efforts still ongoing.}, } @article {pmid26304776, year = {2015}, author = {Boulanger, M and Morlais, F and Bouvier, V and Galateau-Salle, F and Guittet, L and Marquignon, MF and Paris, C and Raffaelli, C and Launoy, G and Clin, B}, title = {Digestive cancers and occupational asbestos exposure: incidence study in a cohort of asbestos plant workers.}, journal = {Occupational and environmental medicine}, volume = {72}, number = {11}, pages = {792-797}, doi = {10.1136/oemed-2015-102871}, pmid = {26304776}, issn = {1470-7926}, mesh = {Adult ; Asbestos ; Cohort Studies ; Digestive System/*pathology ; Digestive System Neoplasms/epidemiology/*etiology ; Esophageal Neoplasms/epidemiology/etiology ; Female ; France/epidemiology ; Humans ; Incidence ; Intestinal Neoplasms/epidemiology/*etiology ; Liver Neoplasms/epidemiology/etiology ; Lung Neoplasms/epidemiology/*etiology ; Male ; Mesothelioma/epidemiology/*etiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Diseases/epidemiology/*etiology ; Occupational Exposure/*adverse effects ; Peritoneal Neoplasms/epidemiology/etiology ; Sex Factors ; }, abstract = {OBJECTIVE: The aim of our study was to estimate the incidence of digestive cancers within a cohort of asbestos-exposed workers.

METHODS: Our study was based on a cohort of 2024 participants occupationally exposed to asbestos. The incidence of digestive cancers was calculated from 1 January 1978 to 31 December 2009 and compared with levels among the local general population using Standardised Incidence Ratios (SIRs). Asbestos exposure was assessed using the company's job-exposure matrix.

RESULTS: 119 cases of digestive cancer were observed within our cohort, for an expected number of 77 (SIR=1.54 (1.28 to 1.85)). A significantly elevated incidence was observed for peritoneal mesothelioma, particularly in women. Significantly elevated incidences were also observed among men for: all digestive cancers, even when excluding peritoneal mesothelioma (SIR=1.50 (1.23 to 1.82)), oesophageal cancer (SIR=1.67 (1.08 to 2.47)) and liver cancer (SIR=1.85 (1.09 to 2.92)). Concerning colorectal cancer, a significant excess of risk was observed for men with exposure duration above 25 years (SIR=1.75 (1.05 to 2.73)).

CONCLUSIONS: Our results are in favour of a link between long-duration asbestos exposure and colorectal cancer in men. They also suggest a relationship between asbestos exposure and cancer of the oesophagus in men. Finally, our results suggest a possible association with small intestine and liver cancers in men.}, } @article {pmid26297204, year = {2015}, author = {Lemjabbar-Alaoui, H and Hassan, OU and Yang, YW and Buchanan, P}, title = {Lung cancer: Biology and treatment options.}, journal = {Biochimica et biophysica acta}, volume = {1856}, number = {2}, pages = {189-210}, pmid = {26297204}, issn = {0006-3002}, support = {U01 CA168878/CA/NCI NIH HHS/United States ; 5U01 CA168878/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Drug Therapy/*trends ; Genetic Predisposition to Disease/genetics ; Humans ; Lung Neoplasms/*physiopathology/*therapy ; Molecular Targeted Therapy/*trends ; Neoplasm Proteins/genetics/*metabolism ; Radiotherapy/*trends ; Treatment Outcome ; }, abstract = {Lung cancer remains the leading cause of cancer mortality in men and women in the U.S. and worldwide. About 90% of lung cancer cases are caused by smoking and the use of tobacco products. However, other factors such as radon gas, asbestos, air pollution exposures, and chronic infections can contribute to lung carcinogenesis. In addition, multiple inherited and acquired mechanisms of susceptibility to lung cancer have been proposed. Lung cancer is divided into two broad histologic classes, which grow and spread differently: small-cell lung carcinomas (SCLCs) and non-small cell lung carcinomas (NSCLCs). Treatment options for lung cancer include surgery, radiation therapy, chemotherapy, and targeted therapy. Therapeutic-modalities recommendations depend on several factors, including the type and stage of cancer. Despite the improvements in diagnosis and therapy made during the past 25 years, the prognosis for patients with lung cancer is still unsatisfactory. The responses to current standard therapies are poor except for the most localized cancers. However, a better understanding of the biology pertinent to these challenging malignancies, might lead to the development of more efficacious and perhaps more specific drugs. The purpose of this review is to summarize the recent developments in lung cancer biology and its therapeutic strategies, and discuss the latest treatment advances including therapies currently under clinical investigation.}, } @article {pmid26290869, year = {2015}, author = {Lin, CK and Chang, YY and Wang, JD and Lee, LJ}, title = {Increased Standardised Incidence Ratio of Malignant Pleural Mesothelioma in Taiwanese Asbestos Workers: A 29-Year Retrospective Cohort Study.}, journal = {BioMed research international}, volume = {2015}, number = {}, pages = {678598}, pmid = {26290869}, issn = {2314-6141}, mesh = {Adult ; Aged ; Asbestos/*toxicity ; Female ; Humans ; Incidence ; Lung Neoplasms/chemically induced/*epidemiology ; Male ; Mesothelioma/chemically induced/*epidemiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/chemically induced/*epidemiology ; Retrospective Studies ; Taiwan ; }, abstract = {OBJECTIVE: This paper aimed to determine the standardised incidence ratio (SIR) of malignant pleural mesothelioma (MPM) in workers exposed to asbestos in Taiwan.

METHODS: All workers employed in asbestos-related factories and registered by the Bureau of Labour Insurance between 1 March, 1950, and 31 December, 1989, were included in the study and were followed from 1 January, 1980, through 31 December, 2009. Incident cases of all cancers, including MPM (ICD-9 code: 163), were obtained from the Taiwan Cancer Registry. SIRs were calculated based on comparison with the incidence rate of the general population of Taiwan and adjusted for age, calendar period, sex, and duration of employment.

RESULTS: The highest SIR of MPM was found for male workers first employed before 1979, with a time since first employment more than 30 years (SIR 4.52, 95% CI: 2.25-8.09). After consideration of duration of employment, the SIR for male MPM was 5.78 (95% CI: 1.19-16.89) for the workers employed for more than 20 years in asbestos-related factories.

CONCLUSIONS: This study corroborates the association between occupational asbestos exposure and MPM. The highest risk of MPM was found among male asbestos workers employed before 1979 and working for more than 20 years in asbestos-related factories.}, } @article {pmid26265669, year = {2016}, author = {Ferrante, D and Mirabelli, D and Tunesi, S and Terracini, B and Magnani, C}, title = {Pleural mesothelioma and occupational and non-occupational asbestos exposure: a case-control study with quantitative risk assessment.}, journal = {Occupational and environmental medicine}, volume = {73}, number = {3}, pages = {147-153}, doi = {10.1136/oemed-2015-102803}, pmid = {26265669}, issn = {1470-7926}, mesh = {Aged ; Asbestos/*adverse effects ; *Carcinogens ; Case-Control Studies ; Construction Industry ; Construction Materials/adverse effects ; Environmental Exposure/*adverse effects ; Environmental Pollution/*adverse effects ; Female ; Housing ; Humans ; Incidence ; Italy ; Logistic Models ; Lung/pathology ; Lung Neoplasms/*etiology ; Male ; Mesothelioma/*etiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Diseases/etiology ; Occupational Exposure/adverse effects ; Odds Ratio ; Pleural Neoplasms/*etiology ; Risk Assessment ; }, abstract = {OBJECTIVES: Casale Monferrato (north west Italy) is an area with an exceptionally high incidence of mesothelioma caused by asbestos contamination at work and in the general environment from the asbestos-cement Eternit plant that was operational until 1986. The purpose of this study was to quantify the association between pleural malignant mesothelioma (PMM) and asbestos cumulative exposure using individual assessment of environmental and domestic exposure, as well as of occupational exposure.

METHODS: This population-based case-control study included cases of PMM diagnosed between January 2001 and June 2006 among residents in the Casale Monferrato Local Health Authority. Population controls were randomly sampled, matched by age and sex to cases. Cumulative exposure was estimated to account for the lifelong exposure history. Analyses were conducted using unconditional logistic regression models adjusting for gender, age at diagnosis and type of interview (direct or proxy respondents).

RESULTS: 200 PMM cases of 223 eligible cases (89.7%) and 348 (63%) of 552 eligible controls accepted to be interviewed. ORs increased with cumulative exposure index (p<0.0001) from 4.4 (CI 95% 1.7 to 11.3) (<1 f/mL-years) to 62.1 (CI 95% 22.2 to 173.2) (≥10 f/mL-years). Among subjects never occupationally exposed, corresponding ORs were 3.8 (CI 95% 1.3 to 11.1) and 23.3 (CI 95% 2.9 to 186.9) (reference: background level of asbestos exposure). ORs of about 2, statistically significant, were observed for domestic exposure and for living in houses near buildings with large asbestos cement parts.

CONCLUSIONS: Risk of PMM increased with cumulative asbestos exposure and also in analyses limited to subjects non-occupationally exposed. Our results also provide indication of risk associated with common sources of environmental exposure and are highly relevant for the evaluation of residual risk after the cessation of asbestos industrial use.}, } @article {pmid26263483, year = {2015}, author = {Kirschner, MB and Pulford, E and Hoda, MA and Rozsas, A and Griggs, K and Cheng, YY and Edelman, JJ and Kao, SC and Hyland, R and Dong, Y and László, V and Klikovits, T and Vallely, MP and Grusch, M and Hegedus, B and Dome, B and Klepetko, W and van Zandwijk, N and Klebe, S and Reid, G}, title = {Fibulin-3 levels in malignant pleural mesothelioma are associated with prognosis but not diagnosis.}, journal = {British journal of cancer}, volume = {113}, number = {6}, pages = {963-969}, pmid = {26263483}, issn = {1532-1827}, mesh = {Adult ; Aged ; Aged, 80 and over ; Animals ; Biomarkers, Tumor/*metabolism ; Case-Control Studies ; Extracellular Matrix Proteins/*metabolism ; Female ; Heterografts ; Humans ; Male ; Mesothelioma/*diagnosis/*metabolism ; Mice ; Mice, Nude ; Middle Aged ; Neoplasm Proteins/*metabolism ; Pleural Effusion/metabolism ; Pleural Neoplasms/*diagnosis/*metabolism ; Prognosis ; }, abstract = {BACKGROUND: Fibulin-3 (FBLN3) was recently presented as a promising novel biomarker for malignant pleural mesothelioma (MPM), warranting independent validation studies.

METHODS: ELISA was used to measure cellular and secreted FBLN3 in cell lines, in plasma of xenograft tumour-bearing mice, in plasma from two independent series of MPM and non-MPM patients and in pleural fluid from a third series. Diagnostic and prognostic potential of FBLN3 was assessed by receiver operating characteristics curve analysis and Kaplan-Meier method, respectively.

RESULTS: FBLN3 was expressed in all MPM and benign mesothelial cell lines tested, and a correlation was observed between cellular protein expression and secreted levels. Human FBLN3 was detectable in plasma of tumour-bearing mice, suggesting that MPM cells contribute to levels of circulating FBLN3. Plasma FBLN3 was significantly elevated in MPM patients from the Sydney cohort, but not the Vienna cohort, but the diagnostic accuracy was low (63%, (95% CI: 50.1-76.4) and 56% (95% CI: 41.5-71.0), respectively). Although FBLN3 levels in pleural effusions were not significantly different between cases and controls, FBLN3 levels in pleural effusion fluid were found to be independently associated with prognosis (hazard ratio of 9.92 (95% CI: 2.14-45.93)).

CONCLUSIONS: These data confirm the potential prognostic value of pleural effusion FBLN3, but question the diagnostic value of this protein in MPM patients.}, } @article {pmid26259877, year = {2015}, author = {Yamagishi, T and Fujimoto, N and Nishi, H and Miyamoto, Y and Hara, N and Asano, M and Fuchimoto, Y and Wada, S and Kitamura, K and Ozaki, S and Kishimoto, T}, title = {Prognostic significance of the lymphocyte-to-monocyte ratio in patients with malignant pleural mesothelioma.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {90}, number = {1}, pages = {111-117}, doi = {10.1016/j.lungcan.2015.07.014}, pmid = {26259877}, issn = {1872-8332}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Biomarkers, Tumor/analysis ; Female ; Humans ; Inflammation/blood/pathology ; Lung Neoplasms/*blood/*pathology/therapy ; Lymphocytes/*pathology ; Male ; Mesothelioma/*blood/*pathology/therapy ; Mesothelioma, Malignant ; Middle Aged ; Monocytes/*pathology ; Neutrophils/pathology ; Prognosis ; ROC Curve ; Retrospective Studies ; }, abstract = {OBJECTIVES: Chronic inflammation plays a key role in the pathogenesis of malignant pleural mesothelioma (MPM) as a result of asbestos exposure. Several inflammation-based prognostic scores including the lymphocyte-to-monocyte ratio (LMR), Glasgow Prognostic Score (GPS), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) reportedly predict survival in many malignancies, while the role of LMR in MPM remains unclear. The aim of this study was to evaluate the clinical value of LMR and to compare the prognostic value of these inflammation-based scores in predicting overall survival (OS) in MPM.

MATERIALS AND METHODS: One hundred and fifty patients with histologically proven MPM were included in this retrospective study. Kaplan-Meier curves and multivariate Cox-regression analyses were calculated for OS. The area under the receiver operating characteristics curve (AUC) was calculated to compare the discriminatory ability of each scoring system.

RESULTS: An elevated LMR was significantly associated with prolonged OS. Patients with LMR <2.74 had significantly poor survival compared with LMR ≥2.74 (median, 5.0 versus 14.0 months; p=0.000). The LMR consistently had a higher AUC value at 6 months (0.722), 12 months (0.712), and 24 months (0.670), compared with other scores. Multivariate analysis showed that the LMR was independently associated with OS.

CONCLUSIONS: The LMR is an independent prognostic marker for OS in patients with MPM and is superior to other inflammation-based prognostic scores with respect to prognostic ability.}, } @article {pmid26248240, year = {2015}, author = {Amorim, E}, title = {Solitary fibrous tumor of the pleura: 3 case reports.}, journal = {Revista da Associacao Medica Brasileira (1992)}, volume = {61}, number = {3}, pages = {207-208}, doi = {10.1590/1806-9282.61.03.207}, pmid = {26248240}, issn = {1806-9282}, mesh = {Humans ; Male ; Middle Aged ; *Solitary Fibrous Tumor, Pleural/pathology/surgery ; Thoracotomy ; }, abstract = {INTRODUCTION: solitary fibrous tumor of the pleura (SFTP) is a rare tumor arising from mesenchymatous cells in submesothelial pleural tissue which, unlike mesothelioma, is not related to asbestos or smoking.

METHODS: report of four patients who underwent surgical treatment for giant SFTP and review of the pertinent literature.

RESULTS: of the four patients operated, two presented symptoms including cough, chest pain and feeling of compression, whereas the other two subjects were asymptomatic. All patients underwent complete surgical resection by wide posterolateral thoracotomy, and surgical specimens removed with minimum bleeding. None of the cases required complementary lobectomy or segmentectomy. All tumors were histologically benign.

CONCLUSION: complete resection of the lesion is the treatment of choice in all SFTP cases. Prognosis of the benign lesion is excellent, although close follow-up is necessary. In the rarer, more aggressive forms, treatment may be complemented by adjunctive chemotherapy or radiotherapy, the benefits of which have yet to be confirmed.}, } @article {pmid26246155, year = {2015}, author = {Emi, M and Yoshikawa, Y and Sato, C and Sato, A and Sato, H and Kato, T and Tsujimura, T and Hasegawa, S and Nakano, T and Hashimoto-Tamaoki, T}, title = {Frequent genomic rearrangements of BRCA1 associated protein-1 (BAP1) gene in Japanese malignant mesothelioma-characterization of deletions at exon level.}, journal = {Journal of human genetics}, volume = {60}, number = {10}, pages = {647-649}, pmid = {26246155}, issn = {1435-232X}, mesh = {Asian People ; *Base Sequence ; *Chromosomal Instability ; Chromosomes, Human, Pair 3/*genetics ; *Exons ; Female ; Humans ; Japan ; Lung Neoplasms/*genetics ; Male ; Mesothelioma/*genetics ; Mesothelioma, Malignant ; *Sequence Deletion ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {Malignant mesothelioma (MM) is an asbestos-related malignancy arising from surface serosal cells of pleural and peritoneal cavities. Somatic mutations of BRCA1 associated protein-1 (BAP1) gene were recently found in MM as well as in uveal melanoma and kidney cancer among the Caucasian and Japanese people. However, frequency of mutations varies among the reported studies, which might be due to presence of undetected gross rearrangements of BAP1 gene that might escape detection by sequencing strategy. We investigated the presence and frequency of gross genomic rearrangements in the BAP1 gene by multiplex ligation-dependent probe amplification (MLPA) in 17 Japanese cases of MM tumors. We found five tumors with partial deletion of BAP1 gene; each tumors displayed partial deletion of exons 1-4 (MM39), exons 1-5 (MM48), exons 11-17 (MM57), exons 1-15 (MM19) and exons 1-16 (MM21). Two tumors (MM34, MM14) had biallelic deletion and four tumors (MM29, MM35, MM45 and MM56) had monoallelic deletion of entire BAP1 gene. Therefore, MLPA analysis revealed large gene rearrangements of BAP1 gene in 65% of MM (11/17). Unusually high frequency of large deletions indicates that the 3p21 chromosomal region surrounding BAP1 gene is structurally unstable. MLPA was useful in characterizing both monoallelic and biallelic deletion of BAP1 gene precisely at exon level.}, } @article {pmid26240051, year = {2016}, author = {Thellung, S and Favoni, RE and Würth, R and Nizzari, M and Pattarozzi, A and Daga, A and Florio, T and Barbieri, F}, title = {Molecular Pharmacology of Malignant Pleural Mesothelioma: Challenges and Perspectives From Preclinical and Clinical Studies.}, journal = {Current drug targets}, volume = {17}, number = {7}, pages = {824-849}, doi = {10.2174/1389450116666150804110714}, pmid = {26240051}, issn = {1873-5592}, mesh = {Animals ; Antineoplastic Agents/pharmacology/*therapeutic use ; Clinical Trials as Topic ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Lung Neoplasms/*drug therapy/pathology ; Mesothelioma/*drug therapy/pathology ; Mesothelioma, Malignant ; Molecular Targeted Therapy ; Neoplastic Stem Cells/*drug effects/pathology ; Pleural Neoplasms/*drug therapy/pathology ; Proto-Oncogene Mas ; Signal Transduction/drug effects ; }, abstract = {Malignant pleural mesothelioma (MPM) is one of the deadliest and most heterogeneous tumors, highly refractory to multimodal therapeutic approach, including surgery, chemo- and radiotherapy. Preclinical and clinical studies exploring the efficacy of drugs targeting tyrosine kinases, angiogenesis and histone deacetylases, did not fulfil the expected clinical benefits. Thus, novel molecular targets should be identified from a definite knowledge of the unique biology and most relevant transduction pathways of MPM cells. Cancer stem cells (CSCs) are a subset of malignant precursors responsible for initiation, progression, resistance to cytotoxic drugs, recurrence and metastatic diffusion of tumor cells. CSCs are putative driving factors for MPM development and contribute to its clinical and biological heterogeneity; hence, targeted eradication of CSCs represents an ineludible goal to counteract MPM aggressiveness. In this context, innovative preclinical models could be exploited to identify novel intracellular pathway inhibitors able to target CSC viability. Novel drug targets have been identified among key factors responsible for the oncogenic transformation of mesothelial cells, often directly induced by asbestos. These include mitogenic and anti-apoptotic signaling that may also be activated by autocrine and paracrine cytokine pathways controlling cell plasticity. Both signaling pathways affecting proto-oncogene and transcription factor expression, or genetic and epigenetic alterations, such as mutations in cell cycle genes and silencing of tumor suppressor genes, represent promising disease-specific targets. In this review we describe current knowledge of MPM cell biology, focusing on potential targets to be tested in pharmacological studies, and highlighting results and challenges of clinical translation.}, } @article {pmid26236392, year = {2015}, author = {Borelli, V and Moura, RR and Trevisan, E and Crovella, S}, title = {NLRP1 and NLRP3 polymorphisms in mesothelioma patients and asbestos exposed individuals a population-based autopsy study from North East Italy.}, journal = {Infectious agents and cancer}, volume = {10}, number = {}, pages = {26}, pmid = {26236392}, issn = {1750-9378}, abstract = {NRLP1 (rs12150220, rs9889625, rs9900356, rs6502867, rs2670660) and NLRP3 (rs35829419, rs10754558) polymorphisms have been analyzed in 69 subjects with documented asbestos exposure and death for malignant pleural mesothelioma and 59 patients with documented asbestos exposure but death for other causes, all from a North East Italy. No association was found between NLRP1 and NLRP3 polymorphisms and susceptibility to develop mesothelioma using the general, dominant or recessive models. Also haplotype analysis did not reveal any significant association with mesothelioma. Our findings, being controversial with respect to another study on Italian patients, do suggest the need of further studies to unravel the contribution of NLRP1 and NLRP3 in susceptibility to mesothelioma.}, } @article {pmid26230599, year = {2015}, author = {Roggli, VL}, title = {The So-called Short-Fiber Controversy: Literature Review and Critical Analysis.}, journal = {Archives of pathology & laboratory medicine}, volume = {139}, number = {8}, pages = {1052-1057}, doi = {10.5858/arpa.2014-0466-RA}, pmid = {26230599}, issn = {1543-2165}, mesh = {Animals ; Asbestos/*adverse effects ; Humans ; Inhalation Exposure/*adverse effects ; Lung Neoplasms/*etiology ; Mineral Fibers/*adverse effects/classification ; Pulmonary Fibrosis/*etiology ; }, abstract = {CONTEXT: Numerous articles in the scientific literature indicate that pathogenic fibers with respect to asbestos-related diseases are those that exceed 5 μm in length. Nonetheless, some authors have expressed concerns regarding pathogenicity of shorter fibers.

OBJECTIVE: To review the scientific evidence regarding pathogenicity (or lack thereof) of fibers less than or equal to 5 μm in length, with particular attention to publications indicating that such fibers might be hazardous.

DATA SOURCES: The scientific literature was reviewed for experimental animal studies and human studies that address the role of fiber size in causation of disease. Sources included original studies, as well as review articles related to the topic.

CONCLUSIONS: Experimental animal studies involving inhalation of fibers have demonstrated that fibers greater than 5 μm in length are associated with both pulmonary fibrosis (ie, asbestosis) and malignancies (carcinoma of the lung and mesothelioma). There is no convincing evidence for a pathogenic effect for fibers that are 5 μm or less in length. Fiber analyses of human lung tissue samples provide further support for pathogenicity of long fibers, particularly the more biopersistent amphibole fibers. Similar observations have been reported for nonasbestos mineral fibers. Concerns expressed by some authors (eg, the greater abundance of short fibers) do not alter these conclusions. Similarly, in vitro studies demonstrating biological activity of short fibers do not override inhalational studies of whole animals or the epidemiological findings in humans.}, } @article {pmid26229210, year = {2015}, author = {Ogunseitan, OA}, title = {The asbestos paradox: global gaps in the translational science of disease prevention.}, journal = {Bulletin of the World Health Organization}, volume = {93}, number = {5}, pages = {359-360}, pmid = {26229210}, issn = {1564-0604}, mesh = {Asbestos/*adverse effects/supply & distribution ; Commerce ; Global Health ; *Health Policy ; Humans ; International Cooperation ; Interprofessional Relations ; Mesothelioma/*chemically induced/*prevention & control ; Translational Research, Biomedical ; }, } @article {pmid26222965, year = {2015}, author = {Frontario, SC and Loveitt, A and Goldenberg-Sandau, A and Liu, J and Roy, D and Cohen, LW}, title = {Primary Peritoneal Mesothelioma Resulting in Small Bowel Obstruction: A Case Report and Review of Literature.}, journal = {The American journal of case reports}, volume = {16}, number = {}, pages = {496-500}, pmid = {26222965}, issn = {1941-5923}, mesh = {Aged ; Female ; Humans ; Intestinal Obstruction/diagnosis/*etiology/therapy ; *Intestine, Small ; Lung Neoplasms/diagnostic imaging/*pathology/therapy ; Mesothelioma/diagnostic imaging/*pathology/therapy ; Mesothelioma, Malignant ; Peritoneal Neoplasms/diagnostic imaging/*pathology/therapy ; Radiography ; }, abstract = {BACKGROUND: Peritoneal mesothelioma is a rare malignancy that affects the serosal surfaces of the peritoneum. The peritoneum is the second most common site of mesothelium affected following the pleura. The aggressive nature and vague presentation pose many obstacles in not only diagnosis but also the treatment of patients with this disease.

CASE REPORT: We present a case of a 76-year-old woman who presented with small bowel obstruction secondary to carcinomatosis secondary to primary peritoneal mesothelioma. The patient had multiple risk factors with asbestos exposure and prior therapeutic radiation.

CONCLUSIONS: We discuss the highly varied and elusive presentation of peritoneal mesothelioma. Cumulative asbestos exposure, either directly or indirectly, remains the leading cause of mesothelioma. However, there are other non-asbestos etiologies. Small bowel obstruction often is a late-presenting symptom of widespread tumor burden. A concise review of the current diagnostic and surgical treatment of primary peritoneal mesothelioma demonstrates that early diagnosis and implementation remains vital.}, } @article {pmid26211743, year = {2015}, author = {Minami, D and Takigawa, N and Kato, Y and Kudo, K and Isozaki, H and Hashida, S and Harada, D and Ochi, N and Fujii, M and Kubo, T and Ohashi, K and Sato, A and Tanaka, T and Hotta, K and Tabata, M and Toyooka, S and Tanimoto, M and Kiura, K}, title = {Downregulation of TBXAS1 in an iron-induced malignant mesothelioma model.}, journal = {Cancer science}, volume = {106}, number = {10}, pages = {1296-1302}, pmid = {26211743}, issn = {1349-7006}, mesh = {8-Hydroxy-2'-Deoxyguanosine ; Animals ; Biomarkers, Tumor/metabolism ; Calbindin 2/metabolism ; Cell Cycle Proteins ; Cell Line, Tumor ; Chromosome Deletion ; Deoxyguanosine/analogs & derivatives/genetics ; Down-Regulation ; Ferric Compounds ; Ferric Oxide, Saccharated ; Glucaric Acid ; Humans ; Iron/*toxicity ; Iron Overload/genetics ; Lung Neoplasms/*chemically induced/*genetics/pathology ; Male ; Membrane Glycoproteins/metabolism ; Mesothelioma/*chemically induced/*genetics/pathology ; Mesothelioma, Malignant ; Neoplasms, Experimental/etiology/genetics/pathology ; Nuclear Proteins/metabolism ; RNA Splicing Factors ; Rats ; Rats, Wistar ; Thromboxane-A Synthase/*genetics ; }, abstract = {Malignant mesothelioma is an aggressive and therapy-resistant neoplasm arising from mesothelial cells. Evidence suggests that the major pathology associated with asbestos-induced mesothelioma is local iron overload. In the present study, we induced iron-induced mesothelioma in rats based on previous reports. Ten Wistar rats were given ferric saccharate and nitrilotriacetate i.p. for 5 days a week. Five of the ten rats exhibited widespread mesotheliomas in the peritoneum and tunica vaginalis. The tumor cells showed positive immunostaining for calretinin, wilms tumor-1, podoplanin and the oxidative DNA marker 8-hydroxy-2'-deoxyguanosine. In three of the five rats with mesothelioma, array-based comparative genomic hybridization analysis identified a common chromosomal deletion mapped to the chromosomal 4q31 locus, which encompasses the TBXAS1 gene. Downregulation of the TBXAS1 gene was confirmed using quantitative PCR. TBXAS1 gene expression was also reduced in three of four human malignant pleural mesothelioma cell lines compared with normal bronchial epithelial cells. Immunohistochemistry revealed that TBXAS1 expression was weakly positive and positive in five and three out of eight human malignant mesothelioma samples, respectively. In conclusion, TBXAS1 gene expression was downregulated in rats with iron-induced mesothelioma. The relationship between iron overload and TBXAS1 downregulation should be pursued further.}, } @article {pmid26202904, year = {2015}, author = {Thomas, A and Chen, Y and Yu, T and Gill, A and Prasad, V}, title = {Distinctive clinical characteristics of malignant mesothelioma in young patients.}, journal = {Oncotarget}, volume = {6}, number = {18}, pages = {16766-16773}, pmid = {26202904}, issn = {1949-2553}, support = {//Intramural NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Asbestos/adverse effects ; Child ; Epithelium/*pathology ; Female ; Genetic Predisposition to Disease ; Humans ; Lung Neoplasms/*diagnosis/*epidemiology/surgery ; Male ; Mesothelioma/*diagnosis/*epidemiology/surgery ; Mesothelioma, Malignant ; Pleural Neoplasms/*diagnosis/*epidemiology/surgery ; Prognosis ; SEER Program ; Young Adult ; }, abstract = {Although considered a disease of the elderly, a subset of patients with mesothelioma are young (<40 years). The goal of this study was to understand their characteristics and outcomes. The Surveillance, Epidemiology, and End Results (SEER) database was used to extract mesothelioma cases (1990-2010). We modeled Kaplan-Meyer survival curves stratified by site of disease, and age of presentation. 2% (207 of 12345) of mesothelioma patients are young. Sex distribution is comparable among the young (51% males, 49% females); males predominated (78%, 22%) in the older cohort. Frequency of pleural and peritoneal mesothelioma are similar in the young (47%, 48% respectively); pleural disease predominated in the old (90%, 9%). Cancer-directed surgeries are more frequent in the young. Regardless of histologic subtype, young patients with pleural (11 vs. 8 months) and peritoneal (not reached vs. 10 months) mesothelioma had significantly improved overall survival. In multivariate analysis, younger age was an independent prognostic factor. Although rare, mesothelioma do occur in the young; their characteristics are distinct from those of older patients. Further studies are needed to understand the interplay between genetic susceptibility and mineral fiber carcinogenesis in the pathogenesis of mesothelioma in the young.}, } @article {pmid26194352, year = {2015}, author = {Järvholm, B and Burdorf, A}, title = {Emerging evidence that the ban on asbestos use is reducing the occurrence of pleural mesothelioma in Sweden.}, journal = {Scandinavian journal of public health}, volume = {43}, number = {8}, pages = {875-881}, pmid = {26194352}, issn = {1651-1905}, mesh = {Adult ; *Asbestos/adverse effects ; Cohort Studies ; Construction Industry/*legislation & jurisprudence ; Female ; Humans ; Incidence ; Lung Neoplasms/chemically induced/*epidemiology ; Male ; Mesothelioma/chemically induced/*epidemiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Diseases/chemically induced/*epidemiology ; Occupational Exposure/adverse effects ; Pleural Neoplasms/chemically induced/*epidemiology ; Registries ; Sweden/epidemiology ; }, abstract = {AIMS: Several countries have banned the use of asbestos. The future health impacts of previous use have been modeled but there are to our knowledge no convincing studies showing a decreased occurrence of asbestos-related diseases due to a ban. The aim of our study was to estimate the effects of the ban and other measures to decrease the use of asbestos in Sweden.

METHODS: The effect was measured through comparing the incidence of pleural malignant mesothelioma in birth cohorts who started to work before and after the decrease in the use of asbestos, i.e. in mid-1970s. Cases were identified through the Swedish Cancer Registry and the analysis was restricted to persons born in Sweden.

RESULTS: Men and women born 1955-79 had a decreased risk of malignant pleural mesothelioma compared to men and women born 1940-49 (RR 0.16, 95% CI 0.11-0.25; and RR 0.47, 95% CI 0.23-0.97 respectively). The decreased use of asbestos prevented each year about 10 cases in men and two cases in women below the age of 57 years in 2012.

CONCLUSIONS: The ban and decreased use of asbestos in Sweden can be measured today in birth cohorts that started their working career after the decrease.}, } @article {pmid26193793, year = {2015}, author = {Lesterhuis, WJ and Rinaldi, C and Jones, A and Rozali, EN and Dick, IM and Khong, A and Boon, L and Robinson, BW and Nowak, AK and Bosco, A and Lake, RA}, title = {Network analysis of immunotherapy-induced regressing tumours identifies novel synergistic drug combinations.}, journal = {Scientific reports}, volume = {5}, number = {}, pages = {12298}, pmid = {26193793}, issn = {2045-2322}, mesh = {Animals ; Antineoplastic Agents/pharmacology/*therapeutic use ; CTLA-4 Antigen/immunology ; Drug Combinations ; Drug Repositioning ; Drug Synergism ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; *Gene Regulatory Networks ; *Immunotherapy ; Mesothelioma/*drug therapy/genetics/*immunology ; Mice, Inbred BALB C ; Remission Induction ; }, abstract = {Cancer immunotherapy has shown impressive results, but most patients do not respond. We hypothesized that the effector response in the tumour could be visualized as a complex network of interacting gene products and that by mapping this network we could predict effective pharmacological interventions. Here, we provide proof of concept for the validity of this approach in a murine mesothelioma model, which displays a dichotomous response to anti-CTLA4 immune checkpoint blockade. Network analysis of gene expression profiling data from responding versus non-responding tumours was employed to identify modules associated with response. Targeting the modules via selective modulation of hub genes or alternatively by using repurposed pharmaceuticals selected on the basis of their expression perturbation signatures dramatically enhanced the efficacy of CTLA4 blockade in this model. Our approach provides a powerful platform to repurpose drugs, and define contextually relevant novel therapeutic targets.}, } @article {pmid26192180, year = {2015}, author = {Wu, WT and Lin, YJ and Li, CY and Tsai, PJ and Yang, CY and Liou, SH and Wu, TN}, title = {Cancer Attributable to Asbestos Exposure in Shipbreaking Workers: A Matched-Cohort Study.}, journal = {PloS one}, volume = {10}, number = {7}, pages = {e0133128}, pmid = {26192180}, issn = {1932-6203}, mesh = {Aged ; Asbestos/*toxicity ; Cohort Studies ; Esophageal Neoplasms/epidemiology/etiology ; Female ; Follow-Up Studies ; Humans ; Incidence ; Lung Neoplasms/epidemiology/etiology ; Male ; Middle Aged ; Neoplasms/epidemiology/*etiology ; Occupational Diseases/*etiology ; *Occupational Exposure ; Proportional Hazards Models ; Risk Assessment ; Risk Factors ; Taiwan/epidemiology ; }, abstract = {PURPOSE: Long-term follow-up studies of asbestos-related cancer in shipbreaking workers are lacking. This study examines the relationship between cancer incidence and asbestos exposure among former Taiwan shipbreaking workers.

METHODS: A total of 4,427 shipbreaking workers and 22,135 population-based matched controls were successfully followed in this study. The study cohort was linked to the Taiwan Cancer Registry for new cancer cases. The adjusted hazard ratio (aHR) for cancer was calculated for the shipbreaking workers with Total Exposure Potential Scores (TEP) for asbestos.

RESULTS: Follow-up generated 109,932 person-years, with 940 deaths and 436 cancer cases, among 4,427 shipbreaking workers from 1985 to 2008. The high asbestos exposure group also had a statistically significant increase in the risk of overall cancer (aHR= 1.71; 95% CI: 1.42-2.05), esophagus cancer (aHR= 2.31; 95% CI: 1.00-5.41), liver and intrahepatic bile duct cancer (aHR= 1.60; 95% CI: 1.08-2.36), and trachea, bronchus, and lung cancer (aHR= 3.08; 95% CI: 1.80-5.25). Mesothelioma cases were found in the high asbestos exposure group. Moreover, overall cancer, esophagus cancer, and trachea, bronchus, and lung cancer were seen in a dose-dependent relationship with asbestos exposure.

CONCLUSIONS: This study presented the elevated trend of asbestos exposure with cancer incidence for overall cancer, esophagus cancer, and trachea, bronchus, and lung cancer among shipbreaking workers. Those workers previously exposed to asbestos should receive persistent monitoring in order to early detect adverse health outcomes.}, } @article {pmid26184317, year = {2015}, author = {Felley-Bosco, E and Opitz, I and Meerang, M}, title = {Hedgehog Signaling in Malignant Pleural Mesothelioma.}, journal = {Genes}, volume = {6}, number = {3}, pages = {500-511}, pmid = {26184317}, issn = {2073-4425}, abstract = {Malignant pleural mesothelioma (MPM) is a cancer associated with exposure to asbestos fibers, which accumulate in the pleural space, damage tissue and stimulate regeneration. Hedgehog signaling is a pathway important during embryonic mesothelium development and is inactivated in adult mesothelium. The pathway is reactivated in some MPM patients with poor clinical outcome, mainly mediated by the expression of the ligands. Nevertheless, mutations in components of the pathway have been observed in a few cases. Data from different MPM animal models and primary culture suggest that both autocrine and paracrine Hedgehog signaling are important to maintain tumor growth. Drugs inhibiting the pathway at the level of the smoothened receptor (Smo) or glioma-associated protein transcription factors (Gli) have been used mostly in experimental models. For clinical development, biomarkers are necessary for the selection of patients who can benefit from Hedgehog signaling inhibition.}, } @article {pmid26179668, year = {2016}, author = {Loharamtaweethong, K and Puripat, N and Aoonjai, N and Sutepvarnon, A and Bandidwattanawong, C}, title = {Anaplastic lymphoma kinase (ALK) translocation in paediatric malignant peritoneal mesothelioma: a case report of novel ALK-related tumour spectrum.}, journal = {Histopathology}, volume = {68}, number = {4}, pages = {603-607}, doi = {10.1111/his.12779}, pmid = {26179668}, issn = {1365-2559}, mesh = {Anaplastic Lymphoma Kinase ; Child ; Female ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Lung Neoplasms/*genetics/*pathology ; Mesothelioma/*genetics/*pathology ; Mesothelioma, Malignant ; Microscopy, Electron, Transmission ; Peritoneal Neoplasms/*genetics/*pathology ; Polymerase Chain Reaction ; Receptor Protein-Tyrosine Kinases/*genetics ; Translocation, Genetic ; }, abstract = {AIMS: To report a case of paediatric malignant peritoneal mesothelioma (MPM) with evidence of anaplastic lymphoma kinase (ALK) translocation.

METHODS AND RESULTS: We describe a 10-year-old girl who presented with abdominal pain and progressive abdominal distension. She had no history of asbestos exposure. Histopathological, immunohistochemical and ultrastructural analyses were performed and showed a biphasic malignant mesothelioma. In addition, we also studied on a selected set of immunomarkers which may be the potential therapeutic molecular targets including ALK, c-kit (CD117), epidermal growth factor receptor (EGFR) and human epidermal growth factor 2 (HER2)/neu, as well as corresponding molecular analysis. Consequently, we identified ALK expression by immunohistochemistry, together with evidence of ALK translocation by fluorescent in-situ hybridization (FISH) analysis.

CONCLUSIONS: Paediatric MPM is associated with ALK translocation in our case. The results may open up a new avenue for the study of molecular genesis of paediatric malignant mesothelioma in the future and help to determine whether patients MMs with ALK translocation would benefit from ALK inhibitor treatment.}, } @article {pmid26174987, year = {2015}, author = {Burkin, DJ and Fontelonga, TM}, title = {Mesothelioma cells breaking bad: loss of integrin α7 promotes cell motility and poor clinical outcomes in patients.}, journal = {The Journal of pathology}, volume = {237}, number = {3}, pages = {282-284}, doi = {10.1002/path.4587}, pmid = {26174987}, issn = {1096-9896}, mesh = {Antigens, CD/*metabolism ; *Cell Movement ; *Epigenesis, Genetic ; Humans ; Integrin alpha Chains/*metabolism ; Lung Neoplasms/*metabolism ; Mesothelioma/*metabolism ; Pleural Neoplasms/*metabolism ; Tumor Suppressor Proteins/*metabolism ; }, abstract = {Mesothelioma is a disease of pleural cells lining the lungs which is often caused by exposure to asbestos. The molecular mechanism(s) that regulate the transformation of pleural mesothelioma cells to a migratory and malignant phenotype are unclear. In recent work published in this journal, Laszlo et al performed a set of elegant experiments to identify a key molecular mechanism that may explain the aggressive nature of this disease. Using patient-derived mesothelioma cells with high versus low migratory activity, the authors conducted a genome-wide expression analysis. They identified a significant reduction in ITGA7 expression only in highly migratory malignant pleural mesothelioma cells and showed that loss of ITGA7 expression was associated with methylation of the promoter. Forced expression of integrin α7 reversed the migratory phenotype of these cells. Finally, the authors identified a strong correlation between ITGA7 expression and patient survival. Together, these results identify expression of integrin α7 as a molecular mechanism for the aggressive migratory transformation of mesothelioma and identify a potentially novel diagnostic and therapeutic target.}, } @article {pmid26163973, year = {2015}, author = {Leuzzi, G and Rea, F and Spaggiari, L and Marulli, G and Sperduti, I and Alessandrini, G and Casiraghi, M and Bovolato, P and Pariscenti, G and Alloisio, M and Infante, M and Pagan, V and Fontana, P and Oliaro, A and Ruffini, E and Ratto, GB and Leoncini, G and Sacco, R and Mucilli, F and Facciolo, F}, title = {Prognostic Score of Long-Term Survival After Surgery for Malignant Pleural Mesothelioma: A Multicenter Analysis.}, journal = {The Annals of thoracic surgery}, volume = {100}, number = {3}, pages = {890-897}, doi = {10.1016/j.athoracsur.2015.04.087}, pmid = {26163973}, issn = {1552-6259}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Mesothelioma/*mortality/*surgery ; Middle Aged ; Pleural Neoplasms/*mortality/*surgery ; *Pneumonectomy/methods ; Prognosis ; Retrospective Studies ; Survival Rate ; Time Factors ; }, abstract = {BACKGROUND: Despite ongoing efforts to improve therapy in malignant pleural mesothelioma, few patients undergoing extrapleural pneumonectomy experience long-term survival (LTS). This study aims to explore predictors of LTS after extrapleural pneumonectomy and to define a prognostic score.

METHODS: From January 2000 to December 2010, we retrospectively reviewed clinicopathologic and oncological factors in a multicenter cohort of 468 malignant pleural mesothelioma patients undergoing extrapleural pneumonectomy. LTS was defined as survival longer than 3 years. Associations were evaluated using χ(2), Student's t, and Mann-Whitney U tests. Logistic regression, Cox regression hazard model, and bootstrap analysis were applied to identify outcome predictors. Survival curves were calculated by the Kaplan-Meier method. Receiver operating characteristic analyses were used to estimate optimal cutoff and area under the curve for accuracy of the model.

RESULTS: Overall, 107 patients (22.9%) survived at least 3 years. Median overall, cancer-specific, and disease-free survival times were 60 (95% confidence interval [CI], 51 to 69), 63 (95% CI, 54 to 72), and 49 months (95% CI, 39 to 58), respectively. At multivariate analysis, age (odds ratio, 0.51; 95% CI, 0.31 to 0.82), epithelioid histology (odds ratio, 7.07; 95% CI, 1.56 to 31.93), no history of asbestos exposure (odds ratio, 3.13; 95% CI, 1.13 to 8.66), and the ratio between metastatic and resected lymph nodes less than 22% (odds ratio, 4.12; 95% CI, 1.68 to 10.12) were independent predictors of LTS. According to these factors, we created a scoring system for LTS that allowed us to correctly predict overall, cancer-specific, and disease-free survival in the total sample, obtaining two different groups with favorable or poor prognosis (area under the curve, 0.74; standard error, 0.04; p < 0.0001).

CONCLUSIONS: Our prognostic model facilitates the prediction of LTS after surgery for malignant pleural mesothelioma and can help to stratify the outcome and, eventually, tailor postoperative treatment.}, } @article {pmid26161391, year = {2015}, author = {Nishimura, Y and Kumagai-Takei, N and Matsuzaki, H and Lee, S and Maeda, M and Kishimoto, T and Fukuoka, K and Nakano, T and Otsuki, T}, title = {Functional Alteration of Natural Killer Cells and Cytotoxic T Lymphocytes upon Asbestos Exposure and in Malignant Mesothelioma Patients.}, journal = {BioMed research international}, volume = {2015}, number = {}, pages = {238431}, pmid = {26161391}, issn = {2314-6141}, mesh = {Asbestos/*adverse effects ; Humans ; Inhalation Exposure/*adverse effects ; Killer Cells, Natural/*immunology ; Lung Neoplasms/*immunology ; Lymphocyte Culture Test, Mixed ; Mesothelioma/*immunology ; Mesothelioma, Malignant ; T-Lymphocytes, Cytotoxic/*immunology ; }, abstract = {Malignant mesothelioma is caused by exposure to asbestos, which is known to have carcinogenic effects. However, the development of mesothelioma takes a long period and results from a low or intermediate dose of exposure. These findings have motivated us to investigate the immunological effects of asbestos exposure and analyze immune functions of patients with mesothelioma and pleural plaque, a sign of exposure to asbestos. Here, we review our knowledge concerning natural killer (NK) cells and cytotoxic T lymphocytes (CTL). NK cells showed impaired cytotoxicity with altered expression of activating receptors upon exposure to asbestos, while induction of granzyme(+) cells in CD8(+) lymphocytes was suppressed by asbestos exposure. It is interesting that a decrease in NKp46, a representative activating receptor, is common between NK cells in PBMC culture with asbestos and those of mesothelioma patients. Moreover, it was observed that CD8(+) lymphocytes may be stimulated by some kind of "nonself" cells in plaque-positive individuals and in mesothelioma patients, whereas CTL in mesothelioma is impaired by poststimulation maintenance of cytotoxicity. These findings suggest that analysis of immunological parameters might contribute to the evaluation of health conditions of asbestos-exposed individuals and to a greater understanding of the pathology of malignant mesothelioma.}, } @article {pmid26156324, year = {2015}, author = {Ak, G and Metintas, S and Akarsu, M and Metintas, M}, title = {The effectiveness and safety of platinum-based pemetrexed and platinum-based gemcitabine treatment in patients with malignant pleural mesothelioma.}, journal = {BMC cancer}, volume = {15}, number = {}, pages = {510}, pmid = {26156324}, issn = {1471-2407}, mesh = {Aged ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use ; Deoxycytidine/administration & dosage/adverse effects/analogs & derivatives ; Female ; Humans ; Karnofsky Performance Status ; Lung Neoplasms/*drug therapy ; Male ; Mesothelioma/*drug therapy ; Mesothelioma, Malignant ; Middle Aged ; Organoplatinum Compounds/administration & dosage/adverse effects ; Pemetrexed/administration & dosage/adverse effects ; Pleural Neoplasms/*drug therapy ; Survival Analysis ; Gemcitabine ; }, abstract = {BACKGROUND: We aimed to evaluate the efficiency and safety of cis/carboplatin plus gemcitabine, which was previously used for mesothelioma but with no recorded proof of its efficiency, compared with cis/carboplatin plus pemetrexed, which is known to be effective in mesothelioma, in comparable historical groups of malignant pleural mesothelioma.

METHODS: One hundred and sixteen patients received cis/carboplatin plus pemetrexed (group 1), while 30 patients received cis/carboplatin plus gemcitabine (group 2) between June 1999 and June 2012. The two groups were compared in terms of median survival and adverse events to chemotherapy.

RESULTS: The mean ages of groups 1 and 2 were 60.7 and 60.8 years, respectively. Most of the patients (78.1%) had epithelial type tumors, and 47% of the patients had stage IV disease. There was no difference between the two groups in terms of age, gender, asbestos exposure, histology, stage, Karnofsky performance status, presence of pleurodesis, prophylactic radiotherapy, second-line chemotherapy and median hemoglobin and serum albumin levels. The median survival time from diagnosis to death or the last day of follow up with a 95% confidence interval was 12 ± 0.95 months (95% CI: 10.15-13.85) for group 1 and 11.0 ± 1.09 months (95% CI: 8.85-13.15) for group 2 (Log-Rank: 0.142; p = 0.706). The median survival time from treatment to death or the last day of follow-up with a 95% confidence interval was 11.0 ± 0.99 months (95% CI: 9.06-12.94) for group 1 and 11.0 ± 1.52 months (95% CI: 8.02-13.97) for group 2 (Log-Rank: 0.584; p = 0.445). The stage and Karnofsky performance status were found to be significant variables on median survival time by univariate analysis. After adjusting for the stage and Karnofsky performance status, the chemotherapy schema was not impressive on median survival time (OR: 0.837; 95% CI: 0.548-1.277; p = 0.409). The progression free survival was 7.0 ± 0.61 months for group I and 6.0 ± 1.56 months for group II (Log-Rank: 0.522; p = 0.470). The treatment was generally well tolerated, and the side effects were similar in both groups.

CONCLUSIONS: The study indicates that platinum-based gemcitabine is effective and a safe schema in malignant pleural mesothelioma. Further research should include large randomized phase III trials comparing these agents.}, } @article {pmid26156176, year = {2015}, author = {Bruno, C and Bruni, B and Scondotto, S and Comba, P}, title = {Prevention of disease caused by fluoro-edenite fibrous amphibole: the way forward.}, journal = {Annali dell'Istituto superiore di sanita}, volume = {51}, number = {2}, pages = {90-92}, doi = {10.4415/ANN_15_02_02}, pmid = {26156176}, issn = {2384-8553}, mesh = {Animals ; Asbestos, Amphibole/*toxicity ; Carcinogens/*toxicity ; Environmental Monitoring ; Humans ; Mesothelioma/chemically induced/*prevention & control ; Neoplasms/chemically induced/*prevention & control ; Occupational Exposure/prevention & control ; Pleural Neoplasms/epidemiology ; Sicily ; }, abstract = {Few months after the publication of the monographic section of Annali dell'Istituto Superiore di Sanità second issue of 2014 "Health impact of fibres with fluoro-edenitic composition", the carcinogenicity of fluoro-edenite was assessed by the International Agency for Research on Cancer (IARC) in the frame of Monograph 111. The IARC Working Group concluded that there is sufficient evidence in humans that exposure to fluoro-edenite fibrous amphibole causes mesothelioma, and sufficient evidence of carcinogenicity in experimental animals. Fluoro-edenite was allocated to Group 1 (the agent is carcinogenic to humans). Now, in view of the recent IARC evaluation, preventive action in Biancavilla requires an upgrade. First of all, environmental monitoring has to be further implemented. All operations of house cleaning should be performed employing wet tools, in order to avoid dust-raising. It is very important that environmental and biological monitoring be related to epidemiological surveillance. The recently approved act of the Sicilian Government concerning a plan of health interventions in Biancavilla will favour cooperation between national, regional and local health institutions with the common goal of improving the quality and appropriateness of diagnostic and therapeutics procedures offered by the health services.}, } @article {pmid26152538, year = {2015}, author = {Petrucci, MS and De Lio, MC and D'Alò, D and Stracci, F and Masanotti, GM}, title = {Epidemiologic surveillance of mesothelioma in Umbria.}, journal = {Annali di igiene : medicina preventiva e di comunita}, volume = {27}, number = {3}, pages = {526-532}, doi = {10.7416/ai.2015.2043}, pmid = {26152538}, issn = {1120-9135}, mesh = {Asbestos/adverse effects ; Carcinogens/toxicity ; Environmental Exposure/adverse effects ; Female ; Humans ; Italy/epidemiology ; Lung Neoplasms/*epidemiology/pathology ; Male ; Mesothelioma/*epidemiology/pathology ; Mesothelioma, Malignant ; Occupational Exposure/adverse effects ; Pleural Neoplasms/*epidemiology/pathology ; Regression Analysis ; Sex Factors ; }, abstract = {BACKGROUND: Malignant mesothelioma (MM) is becoming a prominent health issue due to its low survival and for its increasing incidence in various countries. The objectives of this study were to evaluate epidemiological characteristics and trends of MM in the Umbrian Region for the period 2003-2013.

METHODS: All cases of MM reported to Umbrian Population Cancer Registry between 2003 and 2013. Incidence Annual Standardized Rates (ASRs) were analyzed for all histological types of MM. Estimated Annual Percent Change (APC) and joinpoint regression analysis were used to out light the time trend of MM. Geographical distribution of the relative risk for each municipality was calculated by Standardized Incidence Ratios SIRs.

RESULTS: 191 (156 males) MM cases were recorded in Umbrian residents in the period 2003-2013. Pleural mesothelioma affected 92.1% of the total. Gender ratio M/F was 5.9:1. ASRs for MM was 3.2 among men and 0.6 among women. Joinpoint analysis showed a decrease in females APC -8.4 (95% IC -33.7-26.6) and an increase in males APC 5.8 (95% IC -0.9-13.0). An occupational exposure was identified in 43.7% of females and in 90.7% of males.

CONCLUSIONS: The protracted cancer latency and the continued asbestos existence as environmental contaminant in existing buildings, as well as a carcinogenic risk for the workers involved in removing operations of material containing asbestos justifies the investment in a specific surveillance system. Also important would be to implement a national risk communication strategy addressed to the general population, environment surveillance of the high risk areas and guarantee that all workers involved that even may deal with asbestos are always fully equipped and trained, not only for their individual risk but also for the potential risk of non correct disposal.}, } @article {pmid26150916, year = {2015}, author = {Reid, G}, title = {MicroRNAs in mesothelioma: from tumour suppressors and biomarkers to therapeutic targets.}, journal = {Journal of thoracic disease}, volume = {7}, number = {6}, pages = {1031-1040}, pmid = {26150916}, issn = {2072-1439}, abstract = {Malignant mesothelioma remains a difficult proposition in the clinic, with few accurate molecular markers available to guide diagnosis and patient management, and a dearth of effective treatments. Recent evidence implicates microRNAs-short non-coding RNAs involved in post-transcriptional regulation of gene expression-in mesothelioma biology. Emerging evidence suggests that exploring aberrant microRNA expression will not only improve our understanding of the disease, but will also lead to the identification of new molecular biomarkers and therapeutic targets.}, } @article {pmid26150910, year = {2015}, author = {Batra, H and Antony, VB}, title = {Pleural mesothelial cells in pleural and lung diseases.}, journal = {Journal of thoracic disease}, volume = {7}, number = {6}, pages = {964-980}, pmid = {26150910}, issn = {2072-1439}, abstract = {During development, the mesoderm maintains a complex relationship with the developing endoderm giving rise to the mature lung. Pleural mesothelial cells (PMCs) derived from the mesoderm play a key role during the development of the lung. The pleural mesothelium differentiates to give rise to the endothelium and smooth muscle cells via epithelial-to-mesenchymal transition (EMT). An aberrant recapitulation of such developmental pathways can play an important role in the pathogenesis of disease processes such as idiopathic pulmonary fibrosis (IPF). The PMC is the central component of the immune responses of the pleura. When exposed to noxious stimuli, it demonstrates innate immune responses such as Toll-like receptor (TLR) recognition of pathogen associated molecular patterns as well as causes the release of several cytokines to activate adaptive immune responses. Development of pleural effusions occurs due to an imbalance in the dynamic interaction between junctional proteins, n-cadherin and β-catenin, and phosphorylation of adherens junctions between PMCs, which is caused in part by vascular endothelial growth factor (VEGF) released by PMCs. PMCs play an important role in defense mechanisms against bacterial and mycobacterial pleural infections, and in pathogenesis of malignant pleural effusion, asbestos related pleural disease and malignant pleural mesothelioma. PMCs also play a key role in the resolution of inflammation, which can occur with or without fibrosis. Fibrosis occurs as a result of disordered fibrin turnover and due to the effects of cytokines such as transforming growth factor-β, platelet-derived growth factor (PDGF), and basic fibroblast growth factor; which are released by PMCs. Recent studies have demonstrated a role for PMCs in the pathogenesis of IPF suggesting their potential as a cellular biomarker of disease activity and as a possible therapeutic target. Pleural-based therapies targeting PMCs for treatment of IPF and other lung diseases need further exploration.}, } @article {pmid26147229, year = {2015}, author = {Gao, Z and Hiroshima, K and Wu, X and Zhang, J and Shao, D and Shao, H and Yang, H and Yusa, T and Kiyokawa, T and Kobayashi, M and Shinohara, Y and Røe, OD and Zhang, X and Morinaga, K}, title = {Asbestos textile production linked to malignant peritoneal and pleural mesothelioma in women: Analysis of 28 cases in Southeast China.}, journal = {American journal of industrial medicine}, volume = {58}, number = {10}, pages = {1040-1049}, doi = {10.1002/ajim.22494}, pmid = {26147229}, issn = {1097-0274}, mesh = {Adult ; Aged ; Aged, 80 and over ; Air Pollutants, Occupational/*adverse effects ; Asbestos/*adverse effects ; China/epidemiology ; Female ; Humans ; Lung Neoplasms/diagnosis/epidemiology/*etiology ; Male ; Mesothelioma/diagnosis/epidemiology/*etiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Diseases/diagnosis/epidemiology/*etiology ; Occupational Exposure/*adverse effects/analysis/statistics & numerical data ; Peritoneal Neoplasms/diagnosis/epidemiology/*etiology ; Pleural Neoplasms/diagnosis/epidemiology/*etiology ; Retrospective Studies ; Textile Industry ; }, abstract = {BACKGROUND: Chrysotile had been used in asbestos textile workshops in Southeast China but a clear relation to mesothelioma is lacking.

METHODS: All patients diagnosed with mesothelioma from 2003 to 2010 at Yuyao People's Hospital were re-evaluated by multiple expert pathologists with immunohistochemistry and asbestos exposure data were collected.

RESULTS: Of 43 patients with a mesothelioma diagnosis, 19 peritoneal and nine pleural cases were finally diagnosed as mesothelioma. All were females, and the mean age of the patients with peritoneal or pleural mesothelioma was 52.4 and 58.2 years, respectively. All these cases had a history of domestic or occupational exposure to chrysotile. Two-thirds of the patients were from two adjoining towns with multiple small asbestos textile workshops. Contamination of tremolite was estimated to be less than 0.3%.

CONCLUSIONS: This is a report of mesothelioma in women exposed to chrysotile asbestos at home and at work, with an over-representation of peritoneal mesothelioma.}, } @article {pmid26142533, year = {2015}, author = {Paracha, UZ and Hayat, K and Ali, M and Qadir, MI}, title = {Review: New diagnostic and therapeutic avenues for mesothelioma.}, journal = {Pakistan journal of pharmaceutical sciences}, volume = {28}, number = {4}, pages = {1425-1432}, pmid = {26142533}, issn = {1011-601X}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Complementary Therapies ; Genetic Therapy ; Humans ; Mesothelioma/*diagnosis/mortality/*therapy ; }, abstract = {Mesothelioma is a rare form of cancer affecting the mesothelium lining. It is usually caused by asbestos exposure or exposure to nanofibers. Median survival is less than one year in the mesothelioma patients. Due to its severity, there is a dire necessity to find out new diagnostic and therapeutic strategies. Some recent strategies could help us in fighting against mesothelioma. Diagnostic tools include a range of biomarkers or biotechnological procedure. Therapeutic tools include chemotherapeutic strategies along with immunotherapy, gene therapy and alternative therapy.}, } @article {pmid26140232, year = {2015}, author = {Creaney, J and Ma, S and Sneddon, SA and Tourigny, MR and Dick, IM and Leon, JS and Khong, A and Fisher, SA and Lake, RA and Lesterhuis, WJ and Nowak, AK and Leary, S and Watson, MW and Robinson, BW}, title = {Strong spontaneous tumor neoantigen responses induced by a natural human carcinogen.}, journal = {Oncoimmunology}, volume = {4}, number = {7}, pages = {e1011492}, pmid = {26140232}, issn = {2162-4011}, abstract = {A key to improving cancer immunotherapy will be the identification of tumor-specific "neoantigens" that arise from mutations and augment the resultant host immune response. In this study we identified single nucleotide variants (SNVs) by RNA sequencing of asbestos-induced murine mesothelioma cell lines AB1 and AB1-HA. Using the NetMHCpan 2.8 algorithm, the theoretical binding affinity of predicted peptides arising from high-confidence, exonic, non-synonymous SNVs was determined for the BALB/c strain. The immunoreactivity to 20 candidate mutation-carrying peptides of increased affinity and the corresponding wild-type peptides was determined using interferon-γ ELISPOT assays and lymphoid organs of non-manipulated tumor-bearing mice. A strong endogenous immune response was demonstrated to one of the candidate neoantigens, Uqcrc2; this response was detected in the draining lymph node and spleen. Antigen reactive cells were not detected in non-tumor bearing mice. The magnitude of the response to the Uqcrc2 neoantigen was similar to that of the strong influenza hemagglutinin antigen, a model tumor neoantigen. This work confirms that the approach of RNAseq plus peptide prediction and ELISPOT testing is sufficient to identify natural tumor neoantigens.}, } @article {pmid26139392, year = {2015}, author = {Tunesi, S and Ferrante, D and Mirabelli, D and Andorno, S and Betti, M and Fiorito, G and Guarrera, S and Casalone, E and Neri, M and Ugolini, D and Bonassi, S and Matullo, G and Dianzani, I and Magnani, C}, title = {Gene-asbestos interaction in malignant pleural mesothelioma susceptibility.}, journal = {Carcinogenesis}, volume = {36}, number = {10}, pages = {1129-1135}, doi = {10.1093/carcin/bgv097}, pmid = {26139392}, issn = {1460-2180}, mesh = {Adult ; Aged ; Asbestos/*toxicity ; Female ; *Gene-Environment Interaction ; Genetic Association Studies ; Humans ; Lung Neoplasms/chemically induced/*genetics/pathology ; Male ; Mesothelioma/chemically induced/*genetics/pathology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure ; Pleural Neoplasms/chemically induced/*genetics/pathology ; Polymorphism, Single Nucleotide ; Risk Factors ; }, abstract = {Asbestos exposure is the main risk factor for malignant pleural mesothelioma (MPM), a rare aggressive tumor. Nevertheless, on average less than 10% of subjects highly exposed to asbestos develop MPM, suggesting the possible involvement of other risk factors. To identify the genetic factors that may modulate the risk of MPM, we conducted a gene-environment interaction analysis including asbestos exposure and 15 single nucleotide polymorphisms (SNPs) previously identified through a genome-wide association study on Italian subjects. In the present study, we assessed gene-asbestos interaction on MPM risk using relative excess risk due to interaction and synergy index for additive interaction and V index for multiplicative interaction. Generalized multifactor dimensionality reduction (GMDR) analyses were also performed. Positive deviation from additivity was found for six SNPs (rs1508805, rs2501618, rs4701085, rs4290865, rs10519201, rs763271), and four of them (rs1508805, rs2501618, rs4701085, rs10519201) deviated also from multiplicative models. However, after Bonferroni correction, deviation from multiplicative model was still significant for rs1508805 and rs4701085 only. GMDR analysis showed a strong MPM risk due to asbestos exposure and suggested a possible synergistic effect between asbestos exposure and rs1508805, rs2501618 and rs5756444. Our results suggested that gene-asbestos interaction may play an additional role on MPM susceptibility, given that asbestos exposure appears as the main risk factor.}, } @article {pmid26134238, year = {2015}, author = {Baumann, F and Buck, BJ and Metcalf, RV and McLaurin, BT and Merkler, D and Carbone, M}, title = {Reply to "No Increased Risk for Mesothelioma in Relation to Natural-Occurring Asbestos in Southern Nevada".}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {10}, number = {7}, pages = {e64-5}, pmid = {26134238}, issn = {1556-1380}, support = {P01 CA114047/CA/NCI NIH HHS/United States ; P30 CA071789/CA/NCI NIH HHS/United States ; R01 CA106567/CA/NCI NIH HHS/United States ; }, mesh = {Asbestos/*analysis ; Environmental Exposure/*analysis ; Female ; Humans ; *Inhalation Exposure ; Male ; Mesothelioma/*epidemiology ; }, } @article {pmid26134237, year = {2015}, author = {Pinheiro, PS and Jin, H}, title = {No Increased Risk for Mesothelioma in Relation to Natural-Occurring Asbestos in Southern Nevada.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {10}, number = {7}, pages = {e62-3}, pmid = {26134237}, issn = {1556-1380}, support = {P20 GM103440/GM/NIGMS NIH HHS/United States ; }, mesh = {Asbestos/*analysis ; Environmental Exposure/*analysis ; Female ; Humans ; *Inhalation Exposure ; Male ; Mesothelioma/*epidemiology ; }, } @article {pmid26125439, year = {2015}, author = {Williams, M and Kirschner, MB and Cheng, YY and Hanh, J and Weiss, J and Mugridge, N and Wright, CM and Linton, A and Kao, SC and Edelman, JJ and Vallely, MP and McCaughan, BC and Cooper, W and Klebe, S and Lin, RC and Brahmbhatt, H and MacDiarmid, J and van Zandwijk, N and Reid, G}, title = {miR-193a-3p is a potential tumor suppressor in malignant pleural mesothelioma.}, journal = {Oncotarget}, volume = {6}, number = {27}, pages = {23480-23495}, pmid = {26125439}, issn = {1949-2553}, mesh = {Adenocarcinoma/metabolism ; Animals ; Apoptosis ; Cell Line, Tumor ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Gene Silencing ; Humans ; Lung Neoplasms/genetics/*metabolism ; Mesothelioma/genetics/*metabolism ; Mesothelioma, Malignant ; Mice ; MicroRNAs/*genetics/*metabolism ; Myeloid Cell Leukemia Sequence 1 Protein/*genetics ; Necrosis ; Neoplasm Transplantation ; Pleural Neoplasms/genetics/*metabolism ; Prognosis ; RNA Interference ; Transfection ; }, abstract = {Malignant pleural mesothelioma (MPM) is an asbestos-induced cancer with poor prognosis that displays characteristic alterations in microRNA expression. Recently it was reported that the expression of a subset of microRNAs can distinguish between MPM and adenocarcinoma of the lung. However, the functional importance of these changes has yet to be investigated. We compared expression of miR-192, miR-193a-3p and the miR-200 family in normal pleura and MPM tumor specimens and found a statistically significant reduction in the levels of miR-193a-3p (3.1-fold) and miR-192 (2.8-fold) in MPM. Transfection of MPM cells with a miR-193a-3p mimic resulted in inhibition of growth and an induction of apoptosis and necrosis in vitro. The growth inhibitory effects of miR-193a-3p were associated with a decrease in MCL1 expression and were recapitulated by RNAi-mediated MCL1 silencing. Targeted delivery of miR-193a-3p mimic using EDV minicells inhibited MPM xenograft tumour growth, and was associated with increased apoptosis. In conclusion, miR-193a-3p appears to have importance in the biology of MPM and may represent a target for therapeutic intervention.}, } @article {pmid26119930, year = {2016}, author = {Napolitano, A and Pellegrini, L and Dey, A and Larson, D and Tanji, M and Flores, EG and Kendrick, B and Lapid, D and Powers, A and Kanodia, S and Pastorino, S and Pass, HI and Dixit, V and Yang, H and Carbone, M}, title = {Minimal asbestos exposure in germline BAP1 heterozygous mice is associated with deregulated inflammatory response and increased risk of mesothelioma.}, journal = {Oncogene}, volume = {35}, number = {15}, pages = {1996-2002}, pmid = {26119930}, issn = {1476-5594}, support = {R01 CA198138/CA/NCI NIH HHS/United States ; P30 CA016087/CA/NCI NIH HHS/United States ; P01 CA114047/CA/NCI NIH HHS/United States ; P01CA114047/CA/NCI NIH HHS/United States ; R01CA106567/CA/NCI NIH HHS/United States ; R01 CA160715/CA/NCI NIH HHS/United States ; P30CA071789/CA/NCI NIH HHS/United States ; R01 CA106567/CA/NCI NIH HHS/United States ; R01CA160715-0A/CA/NCI NIH HHS/United States ; P30 CA071789/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Asbestos, Crocidolite/administration & dosage/*toxicity ; Ascitic Fluid/chemistry ; Chemokines/analysis ; Cytokines/analysis ; Dose-Response Relationship, Drug ; Female ; Genetic Predisposition to Disease ; Germ-Line Mutation ; Heterozygote ; Leukocytes/pathology ; Macrophages, Peritoneal/classification/physiology ; Male ; Mesothelioma/*etiology/genetics ; Mice ; Mice, Inbred C57BL ; Mineral Fibers/toxicity ; Peritoneal Neoplasms/*etiology/genetics ; Peritonitis/etiology/genetics ; Random Allocation ; Tumor Suppressor Proteins/deficiency/*genetics/physiology ; Ubiquitin Thiolesterase/deficiency/*genetics/physiology ; }, abstract = {Germline BAP1 mutations predispose to several cancers, in particular malignant mesothelioma. Mesothelioma is an aggressive malignancy generally associated with professional exposure to asbestos. However, to date, we found that none of the mesothelioma patients carrying germline BAP1 mutations were professionally exposed to asbestos. We hypothesized that germline BAP1 mutations might influence the asbestos-induced inflammatory response that is linked to asbestos carcinogenesis, thereby increasing the risk of developing mesothelioma after minimal exposure. Using a BAP1(+/-) mouse model, we found that, compared with their wild-type littermates, BAP1(+/-) mice exposed to low-dose asbestos fibers showed significant alterations of the peritoneal inflammatory response, including significantly higher levels of pro-tumorigenic alternatively polarized M2 macrophages, and lower levels of several chemokines and cytokines. Consistent with these data, BAP1(+/-) mice had a significantly higher incidence of mesothelioma after exposure to very low doses of asbestos, doses that rarely induced mesothelioma in wild-type mice. Our findings suggest that minimal exposure to carcinogenic fibers may significantly increase the risk of malignant mesothelioma in genetically predisposed individuals carrying germline BAP1 mutations, possibly via alterations of the inflammatory response.}, } @article {pmid26115838, year = {2015}, author = {Stephens, RJ and Whiting, C and Cowan, K and , }, title = {Research priorities in mesothelioma: A James Lind Alliance Priority Setting Partnership.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {89}, number = {2}, pages = {175-180}, doi = {10.1016/j.lungcan.2015.05.021}, pmid = {26115838}, issn = {1872-8332}, mesh = {Humans ; *Lung Neoplasms/diagnosis/therapy ; *Mesothelioma/diagnosis/therapy ; Mesothelioma, Malignant ; *Research ; }, abstract = {BACKGROUND: In the UK, despite the import and use of all forms of asbestos being banned more than 15 years ago, the incidence of mesothelioma continues to rise. Mesothelioma is almost invariably fatal, and more research is required, not only to find more effective treatments, but also to achieve an earlier diagnosis and improve palliative care. Following a debate in the House of Lords in July 2013, a package of measures was agreed, which included a James Lind Alliance Priority Setting Partnership, funded by the National Institute for Health Research. The partnership brought together patients, carers, health professionals and support organisations to agree the top 10 research priorities relating to the diagnosis, treatment and care of patients with mesothelioma.

METHODS: Following the established James Lind Alliance priority setting process, mesothelioma patients, current and bereaved carers, and health professionals were surveyed to elicit their concerns regarding diagnosis, treatment and care. Research questions were generated from the survey responses, and following checks that the questions were currently unanswered, an interim prioritisation survey was conducted to identify a shortlist of questions to take to a final consensus meeting.

FINDINGS: Four hundred and fifty-three initial surveys were returned, which were refined into 52 unique unanswered research questions. The interim prioritisation survey was completed by 202 responders, and the top 30 questions were taken to a final meeting where mesothelioma patients, carers, and health professionals prioritised all the questions, and reached a consensus on the top 10.

INTERPRETATION: The top 10 questions cover a wide portfolio of research (including assessing the value of immunotherapy, individualised chemotherapy, second-line treatment and immediate chemotherapy, monitoring patients with pleural thickening, defining the management of ascites in peritoneal mesothelioma, and optimising follow-up strategy). This list is an invaluable resource, which should be used to inform the prioritisation and funding of future mesothelioma research.}, } @article {pmid26111538, year = {2016}, author = {Yu, M and Chen, R and Jia, Z and Chen, J and Lou, J and Tang, S and Zhang, X}, title = {MWCNTs Induce ROS Generation, ERK Phosphorylation, and SOD-2 Expression in Human Mesothelial Cells.}, journal = {International journal of toxicology}, volume = {35}, number = {1}, pages = {17-26}, doi = {10.1177/1091581815591223}, pmid = {26111538}, issn = {1092-874X}, mesh = {Cell Line, Transformed ; Epithelium/enzymology/*metabolism ; Extracellular Signal-Regulated MAP Kinases/*metabolism ; Humans ; Microscopy, Electron, Transmission ; *Nanotubes, Carbon ; Phosphorylation ; Reactive Oxygen Species/*metabolism ; Superoxide Dismutase/*metabolism ; }, abstract = {Biological oxidative responses are involved in the toxicity of multiwall carbon nanotubes (MWCNTs), which may cause asbestos-like pathogenicity. Superoxide dismutase 2 (SOD-2) has been proposed as a biomarker of early responses to mesothelioma-inducing fibers. This study was conducted to investigate the alteration of SOD-2 expression in the human mesothelial cell lines Met-5A after exposure to nontoxic doses of MWCNTs and the potential signaling pathway. The parameters measured included the viability, morphological change, superoxide formation, extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation, and messenger RNA (mRNA)/protein levels of SOD-2. Our results showed that MWCNTs upregulated SOD-2 expression at both mRNA and protein level. Coincidently, both superoxide formation and ERK1/2 phosphorylation were observed in Met-5A cells exposed to MWCNTs and were diminished by pretreatment with the reactive oxidative species (ROS) scavenger, N-acetyl-l-(+)-cysteine (NAC). To further investigate the role of ROS/ERK1/2 in MWCNTs-induced SOD-2 overexpression, prior to MWCNTs exposure, cells were pretreated with the Mitogen-activated protein kinase kinase 1/2 (MEK 1/2) inhibitor (U0126) or with NAC. Both pretreatments decreased the MWCNTs-induced overexpression of SOD-2. These results suggest that upregulation of SOD-2 in Met-5A cells exposed to MWCNTs is mediated by ROS formation and ERK1/2 activation.}, } @article {pmid26109114, year = {2015}, author = {Van den Borre, L and Deboosere, P}, title = {Enduring health effects of asbestos use in Belgian industries: a record-linked cohort study of cause-specific mortality (2001-2009).}, journal = {BMJ open}, volume = {5}, number = {6}, pages = {e007384}, pmid = {26109114}, issn = {2044-6055}, mesh = {Adolescent ; Adult ; Aged ; Asbestos/*toxicity ; Asbestosis/mortality ; Belgium/epidemiology ; Cohort Studies ; Humans ; Industry/statistics & numerical data ; Laryngeal Neoplasms/mortality ; Lung Neoplasms/epidemiology ; Male ; Mesothelioma/mortality ; Middle Aged ; Mouth Neoplasms/mortality ; Occupational Diseases/*mortality ; Occupational Exposure/adverse effects ; Young Adult ; }, abstract = {OBJECTIVE: To investigate cause-specific mortality among asbestos workers and potentially exposed workers in Belgium and evaluate potential excess in mortality due to established and suspected asbestos-related diseases.

DESIGN: This cohort study is based on an individual record linkage between the 1991 Belgian census and cause-specific mortality information for Flanders and Brussels (2001-2009).

SETTING: Belgium (Flanders and Brussels region).

PARTICIPANTS: The study population consists of 1,397,699 male workers (18-65,years) with 72,074 deaths between 1 October 2001 and 31 December 2009. Using a classification of high-risk industries, mortality patterns between 2056 asbestos workers, 385,046 potentially exposed workers and the working population have been compared.

OUTCOME MEASURES: Standardised mortality ratios (SMRs) and 95% CIs are calculated for manual and non-manual workers.

RESULTS: Our findings show clear excess in asbestos-related mortality in the asbestos industry with SMRs for mesothelioma of 4071 (CI 2327 to 6611) among manual workers and of 4489 (CI 1458 to 10,476) among non-manual workers. Excess risks in asbestos-related mortality are also found in the chemical industry, the construction industry, the electrical generation and distribution industry, the basic metals manufacturing industry, the metal products manufacturing industry, the railroad industry, and the shipping industry. Oral cancer mortality is significantly higher for asbestos workers (SMR 383; CI 124 to 894), railroad workers (SMR 192; CI 112 to 308), shipping workers (SMR 172; CI 102 to 271) and construction workers (SMR 125; CI 100 to 153), indicating a possible association with occupational asbestos exposure. Workers in all four industries have elevated mortality rates for cancer of the mouth. Only construction workers experience significantly higher pharyngeal cancer mortality (SMR 151; CI 104 to 212).

CONCLUSIONS: The study identifies vulnerable groups of Belgian asbestos workers, demonstrating the current-day health repercussions of historical asbestos use. Results support the hypothesis of a possible association between the development of oral cancer and occupational asbestos exposure.}, } @article {pmid26108245, year = {2016}, author = {Galetta, D and Catino, A and Misino, A and Logroscino, A and Fico, M}, title = {Sarcomatoid mesothelioma: future advances in diagnosis, biomolecular assessment, and therapeutic options in a poor-outcome disease.}, journal = {Tumori}, volume = {102}, number = {2}, pages = {127-130}, doi = {10.5301/tj.5000364}, pmid = {26108245}, issn = {2038-2529}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Asbestos/toxicity ; Carcinogens/toxicity ; Humans ; Lung Neoplasms/*diagnosis/drug therapy/*genetics/mortality/pathology ; Mesothelioma/*diagnosis/drug therapy/*genetics/mortality/pathology ; Mesothelioma, Malignant ; MicroRNAs/*analysis ; Neoplasm Staging ; Pleural Neoplasms/*diagnosis/drug therapy/*genetics/mortality/pathology ; Predictive Value of Tests ; Prognosis ; Survival Rate ; }, abstract = {Malignant pleural mesothelioma (MPM) is the most frequent pleural neoplasm, with asbestos exposure as one of the recognized carcinogen agents, causative in 80% of cases. The prognosis is poor; median survival of untreated cases is 6-9 months, with fewer than 5% of patients surviving 5 years. Sarcomatoid mesothelioma (SM) represents the subtype with the worst outcome and median survival ranging from 3.5 to 8 months. In the last few years, an accurate differentiation between the subtypes of MPM has become a crucial issue, due to differences in chemosensitivity and clinical outcome, and several studies have evaluated different immunohistochemical markers to better define the diagnosis. The different and worse outcome of patients with SM and, in general, nonepithelioid subtypes makes it intriguing to select these cases to better study the biomolecular profile in order to find factors linked to prognosis and/or predictive of therapeutic response. Considering recent studies on miRNA and genetic mapping, further investigation of this rare subtype might represent a field for basic and clinical-translational research providing for more tailored therapies.}, } @article {pmid26106244, year = {2015}, author = {Lange, JH and Cegolon, L}, title = {Non-asbestos Causes of mesothelioma and translocation of asbestos fibres.}, journal = {Singapore medical journal}, volume = {56}, number = {6}, pages = {361}, pmid = {26106244}, issn = {2737-5935}, mesh = {Humans ; Lung Neoplasms/*diagnosis ; Male ; Mesothelioma/*diagnosis ; Testicular Hydrocele/*diagnosis ; Testicular Neoplasms/*diagnosis ; }, } @article {pmid26100969, year = {2015}, author = {Hjerpe, A and Ascoli, V and Bedrossian, CW and Boon, ME and Creaney, J and Davidson, B and Dejmek, A and Dobra, K and Fassina, A and Field, A and Firat, P and Kamei, T and Kobayashi, T and Michael, CW and Önder, S and Segal, A and Vielh, P and , and , }, title = {Guidelines for the cytopathologic diagnosis of epithelioid and mixed-type malignant mesothelioma: Complementary Statement from the International Mesothelioma Interest Group, Also Endorsed by the International Academy of Cytology and the Papanicolaou Society of Cytopathology.}, journal = {Diagnostic cytopathology}, volume = {43}, number = {7}, pages = {563-576}, doi = {10.1002/dc.23271}, pmid = {26100969}, issn = {1097-0339}, mesh = {Adenocarcinoma/diagnosis/pathology ; *Cytodiagnosis ; Diagnosis, Differential ; Histocytochemistry/standards ; Humans ; International Cooperation ; Lung Neoplasms/*diagnosis/pathology ; Mesothelioma/*diagnosis/pathology ; Mesothelioma, Malignant ; Neoplasms/diagnosis/pathology ; Pleural Effusion/*diagnosis/pathology ; Specimen Handling/*standards ; Staining and Labeling/standards ; }, abstract = {OBJECTIVE: To provide practical guidelines for the cytopathologic diagnosis of malignant mesothelioma.

DATA SOURCES: Cytopathologists with an interest in the field involved in the International Mesothelioma Interest Group (IMIG) and the International Academy of Cytology (IAC) contributed to this update. Reference material includes peer-reviewed publications and textbooks.

RATIONALE: This article is the result of discussions during and after the IMIG 2012 conference in Boston, followed by thorough discussions during the 2013 IAC meeting in Paris. Additional contributions have been obtained from cytopathologists and scientists who could not attend these meetings, with final discussions and input during the IMIG 2014 conference in Cape Town.}, } @article {pmid26090445, year = {2015}, author = {Maruyama, K and Haniu, H and Saito, N and Matsuda, Y and Tsukahara, T and Kobayashi, S and Tanaka, M and Aoki, K and Takanashi, S and Okamoto, M and Kato, H}, title = {Endocytosis of Multiwalled Carbon Nanotubes in Bronchial Epithelial and Mesothelial Cells.}, journal = {BioMed research international}, volume = {2015}, number = {}, pages = {793186}, pmid = {26090445}, issn = {2314-6141}, mesh = {Apoptosis/drug effects ; Asbestos/toxicity ; Autophagy/drug effects ; Bronchi/drug effects/pathology ; Endocytosis/*drug effects ; Epithelial Cells/drug effects/*pathology ; Humans ; Mesothelioma/chemically induced/*pathology ; Nanotubes, Carbon/*adverse effects ; Reactive Oxygen Species/metabolism ; }, abstract = {Bronchial epithelial cells and mesothelial cells are crucial targets for the safety assessment of inhalation of carbon nanotubes (CNTs), which resemble asbestos particles in shape. Intrinsic properties of multiwalled CNTs (MWCNTs) are known to cause potentially hazardous effects on intracellular and extracellular pathways. These interactions alter cellular signaling and affect major cell functions, resulting in cell death, lysosome injury, reactive oxygen species production, apoptosis, and cytokine release. Furthermore, CNTs are emerging as a novel class of autophagy inducers. Thus, in this study, we focused on the mechanisms of MWCNT uptake into the human bronchial epithelial cells (HBECs) and human mesothelial cells (HMCs). We verified that MWCNTs are actively internalized into HBECs and HMCs and were accumulated in the lysosomes of the cells after 24-hour treatment. Next, we determined which endocytosis pathways (clathrin-mediated, caveolae-mediated, and macropinocytosis) were associated with MWCNT internalization by using corresponding endocytosis inhibitors, in two nonphagocytic cell lines derived from bronchial epithelial cells and mesothelioma cells. Clathrin-mediated endocytosis inhibitors significantly suppressed MWCNT uptake, whereas caveolae-mediated endocytosis and macropinocytosis were also found to be involved in MWCNT uptake. Thus, MWCNTs were positively taken up by nonphagocytic cells, and their cytotoxicity was closely related to these three endocytosis pathways.}, } @article {pmid26083165, year = {2015}, author = {Terracini, B and Pedra, F and Otero, U}, title = {Asbestos-related cancers in Brazil.}, journal = {Cadernos de saude publica}, volume = {31}, number = {5}, pages = {903-905}, doi = {10.1590/0102-311XPE010515}, pmid = {26083165}, issn = {1678-4464}, mesh = {Asbestos/*adverse effects/*toxicity ; Brazil ; Carcinogens/*toxicity ; Environmental Exposure/adverse effects ; Humans ; Mesothelioma/diagnosis/*etiology ; Occupational Diseases/diagnosis/*etiology ; Pleural Neoplasms/diagnosis/*etiology ; }, } @article {pmid26082103, year = {2015}, author = {Kubo, S and Takagi-Kimura, M and Kasahara, N}, title = {Combinatorial anti-angiogenic gene therapy in a human malignant mesothelioma model.}, journal = {Oncology reports}, volume = {34}, number = {2}, pages = {633-638}, doi = {10.3892/or.2015.4058}, pmid = {26082103}, issn = {1791-2431}, mesh = {Angiogenesis Inhibitors/*genetics ; Angiostatins/genetics/metabolism ; Animals ; Cell Line, Tumor ; Cell Proliferation ; Endostatins/genetics/metabolism ; Genetic Therapy/*methods ; Genetic Vectors/*administration & dosage ; Humans ; Lentivirus/*genetics ; Mesothelioma/genetics/*therapy ; Mice ; Receptor, Fibroblast Growth Factor, Type 2/genetics/metabolism ; }, abstract = {Anti-angiogenic gene therapy represents a promising strategy for cancer; however, it has rarely been tested in malignant mesothelioma, a highly aggressive tumor associated with asbestos with poor prognosis. In the present study, we investigated whether anti-angiogenic factors such as angiostatin, endostatin and the soluble form of vascular endothelial growth factor receptor 2 (sFlk1) were able to inhibit endothelial cell proliferation via lentivirus-mediated gene transfer into malignant mesothelioma cells in culture. We also assessed whether a dual-agent strategy had greater therapeutic benefit. Human malignant pleural mesothelioma MSTO-211H cells were transduced using lentiviral vectors that individually expressed angiostatin, endostatin and sFlk1 and linked to enhanced green fluorescent protein (EGFP) marker gene expression via an internal ribosome entry site. The lentivirus expressing EGFP alone was used as a control. The resultant cells designated as MSTO-A, MSTO-E, MSTO-F and MSTO-C were confirmed by western blot analysis and fluorescence microscopy to stably express the corresponding proteins. No differences were observed in the in vitro growth rates between any of these cells. However, co-culture of MSTO-A, MSTO-E and MSTO-F showed significant suppression of human umbilical endothelial cell growth in vitro compared with that of MSTO-C. Furthermore, a combination of any two among MSTO-A, MSTO-E and MSTO-F significantly enhanced efficacy. These results suggest that combinatorial anti-angiogenic gene therapy targeting different pathways of endothelial growth factor signaling has the potential for greater therapeutic efficacy than that of a single-agent regimen.}, } @article {pmid26078352, year = {2015}, author = {Benedetti, S and Nuvoli, B and Catalani, S and Galati, R}, title = {Reactive oxygen species a double-edged sword for mesothelioma.}, journal = {Oncotarget}, volume = {6}, number = {19}, pages = {16848-16865}, pmid = {26078352}, issn = {1949-2553}, mesh = {Cell Transformation, Neoplastic/metabolism ; Humans ; Mesothelioma/*etiology/*pathology ; Nanotubes, Carbon/*adverse effects ; Oxidative Stress/*physiology ; Reactive Oxygen Species/*adverse effects ; }, abstract = {It is well known that oxidative stress can lead to chronic inflammation which, in turn, could mediate most chronic diseases including cancer. Oxidants have been implicated in the activity of crocidolite and amosite, the most powerful types of asbestos associated to the occurrence of mesothelioma. Currently rates of mesothelioma are rising and estimates indicate that the incidence of mesothelioma will peak within the next 10-15 years in the western world, while in Japan the peak is predicted not to occur until 40 years from now. Although the use of asbestos has been banned in many countries around the world, production of and the potentially hazardous exposure to asbestos is still present with locally high incidences of mesothelioma. Today a new man-made material, carbon nanotubes, has arisen as a concern; carbon nanotubes may display 'asbestos-like' pathogenicity with mesothelioma induction potential. Carbon nanotubes resulted in the greatest reactive oxygen species generation. How oxidative stress activates inflammatory pathways leading to the transformation of a normal cell to a tumor cell, to tumor cell survival, proliferation, invasion, angiogenesis, chemoresistance, and radioresistance, is the aim of this review.}, } @article {pmid26076085, year = {2015}, author = {Grzankowski, KS and Brightwell, RM and Kasznica, JM and Odusi, KO}, title = {Malignant peritoneal mesothelioma without asbestos exposure: An ovarian cancer imitator.}, journal = {Gynecologic oncology reports}, volume = {11}, number = {}, pages = {10-12}, pmid = {26076085}, issn = {2352-5789}, support = {P30 CA016056/CA/NCI NIH HHS/United States ; T32 CA108456/CA/NCI NIH HHS/United States ; }, abstract = {•Malignant peritoneal mesothelioma is a rare aggressive tumor with approximately 400 new cases annually in the US.•In optimal cytoreduction HIPEC is the standard treatment.•In suboptimal cytoreduction IV cisplatin and pemetrexed have high efficacy.}, } @article {pmid26075933, year = {2015}, author = {Maxim, LD and Niebo, R and Utell, MJ}, title = {Are pleural plaques an appropriate endpoint for risk analyses?.}, journal = {Inhalation toxicology}, volume = {27}, number = {7}, pages = {321-334}, doi = {10.3109/08958378.2015.1051640}, pmid = {26075933}, issn = {1091-7691}, mesh = {Air Pollutants, Occupational/*toxicity ; Asbestos/toxicity ; Humans ; Lung Neoplasms/epidemiology ; Occupational Diseases/diagnosis/*epidemiology/physiopathology ; Occupational Exposure/*adverse effects ; Pleural Diseases/diagnosis/*epidemiology/physiopathology ; Risk Assessment ; }, abstract = {This review summarizes the literature on the relation between the development of pleural plaques and non-malignant and malignant disease in cohorts exposed to asbestos and other fibers. The available evidence indicates that, absent any other pleural disease, the presence of pleural plaques does not result in respiratory symptoms or clinically significant impacts on lung function. For certain types of asbestos, the development of pleural plaques is statistically correlated with malignant disease, but the evidence is consistent with the hypothesis that pleural plaques without other pleural disease are a marker of exposure, rather than an independent risk factor. Pleural plaques have also developed in cohorts exposed to other fibers that have not proven to be carcinogenic. Risk analyses should be based on the avoidance of known adverse conditions, rather than pleural plaques per se.}, } @article {pmid26075427, year = {2015}, author = {Kao, SC and Fulham, M and Wong, K and Cooper, W and Brahmbhatt, H and MacDiarmid, J and Pattison, S and Sagong, JO and Huynh, Y and Leslie, F and Pavlakis, N and Clarke, S and Boyer, M and Reid, G and van Zandwijk, N}, title = {A Significant Metabolic and Radiological Response after a Novel Targeted MicroRNA-based Treatment Approach in Malignant Pleural Mesothelioma.}, journal = {American journal of respiratory and critical care medicine}, volume = {191}, number = {12}, pages = {1467-1469}, doi = {10.1164/rccm.201503-0461LE}, pmid = {26075427}, issn = {1535-4970}, mesh = {Humans ; Lung/diagnostic imaging ; Lung Neoplasms/*diagnostic imaging/*drug therapy ; Male ; Mesothelioma/*diagnostic imaging/*drug therapy ; Mesothelioma, Malignant ; MicroRNAs/*therapeutic use ; Middle Aged ; Tomography, X-Ray Computed ; Treatment Outcome ; }, } @article {pmid26070993, year = {2015}, author = {Pawełczyk, A and Božek, F}, title = {Health risk associated with airborne asbestos.}, journal = {Environmental monitoring and assessment}, volume = {187}, number = {7}, pages = {428}, pmid = {26070993}, issn = {1573-2959}, mesh = {Air Pollutants/*analysis/toxicity ; Asbestos/*analysis/toxicity ; Environmental Exposure/*analysis/statistics & numerical data ; Environmental Monitoring ; Humans ; Lung Neoplasms/*chemically induced ; Mesothelioma/*chemically induced ; Poland ; Risk Assessment/statistics & numerical data ; Uncertainty ; }, abstract = {The following paper presents an assessment of health risks associated with air polluted with respirable asbestos fibers in towns of southwest Poland. The aim of the work was to determine whether or not any prevention measures are necessary in order to reduce the level of exposure to the pollutant. The risk assessment was carried out based on the air analyses and the latest asbestos toxicity data published by the Environmental Protection Agency (US EPA), USA and Office of Environmental Health Hazard Assessment (OEHHA). It was found that in some sites, the concentration of the asbestos fibers exceeded the acceptable levels, which should be a reason of special concern. The highest concentration of asbestos was found in town centers during the rush hours. In three spots, the calculated maximum health risk exceeded 1E-04 which is considered too high according to the adopted standards. So far, it has not yet been possible to find a reasonable method of ensuring the hazard reduction.}, } @article {pmid26059286, year = {2015}, author = {Acencio, MM and Soares, B and Marchi, E and Silva, CS and Teixeira, LR and Broaddus, VC}, title = {Inflammatory Cytokines Contribute to Asbestos-Induced Injury of Mesothelial Cells.}, journal = {Lung}, volume = {193}, number = {5}, pages = {831-837}, pmid = {26059286}, issn = {1432-1750}, mesh = {Animals ; Apoptosis/drug effects ; Asbestos, Crocidolite/*toxicity ; Asbestos, Serpentine/*toxicity ; Cell Survival/drug effects ; Cells, Cultured ; Chemokine CXCL2/antagonists & inhibitors/metabolism ; Cytokines/antagonists & inhibitors/*metabolism ; Epithelial Cells/drug effects/*metabolism/*pathology ; Interleukin-1beta/antagonists & inhibitors/metabolism ; Interleukin-6/antagonists & inhibitors/metabolism ; Mice ; Necrosis/chemically induced ; Pleura/cytology ; }, abstract = {BACKGROUND: Several diseases have been related to asbestos exposure, including the pleural tumor mesothelioma. The mechanism of pleural injury by asbestos fibers is not yet fully understood. The inflammatory response with release of mediators leading to a dysregulation of apoptosis may play a pivotal role in the pathophysiology of asbestos-induced pleural disease.

OBJECTIVE: To determine whether pro-inflammatory cytokines produced by asbestos-exposed pleural mesothelial cells modify the injury induced by the asbestos.

METHODS: Mouse pleural mesothelial cells (PMC) were exposed to crocidolite or chrysotile asbestos fibers (3.0 μg/cm(2)) for 4, 24, or 48 h and assessed for viability, necrosis and apoptosis, and the production of cytokines IL-1β, IL-6 and macrophage inflammatory protein-2 (MIP-2). Cells exposed to fibers were also treated with antibodies anti-IL-1β, anti-IL-6, anti- IL-1β+anti-IL-6 or anti-MIP-2 or their irrelevant isotypes, and assessed for apoptosis and necrosis. Non-exposed cells and cells treated with wollastonite, an inert particle, were used as controls.

RESULTS: Mesothelial cells exposed to either crocidolite or chrysotile underwent both apoptosis and necrosis and released cytokines IL-1β, IL-6 and MIP-2. In the crocidolite group, apoptosis and the levels of all cytokines were higher than in the chrysotile group, at comparable concentrations. Neutralization of IL-1β andIL-6, but not MIP-2, inhibited apoptosis and necrosis, especially in the cells exposed to crocidolite fibers.

CONCLUSIONS: Both crocidolite and chrysotile asbestos fibers induced apoptosis and produced an acute inflammatory response characterized by elevated levels of IL-1β, IL-6 and MIP-2 in cultured mouse PMC. IL-1β and IL-6, but not MIP-2, were shown to contribute to asbestos-induced injury, especially in the crocidolite group.}, } @article {pmid26057448, year = {2015}, author = {Jennings, CJ and Murer, B and O'Grady, A and Hearn, LM and Harvey, BJ and Kay, EW and Thomas, W}, title = {Differential p16/INK4A cyclin-dependent kinase inhibitor expression correlates with chemotherapy efficacy in a cohort of 88 malignant pleural mesothelioma patients.}, journal = {British journal of cancer}, volume = {113}, number = {1}, pages = {69-75}, pmid = {26057448}, issn = {1532-1827}, mesh = {Cell Line, Tumor ; Cohort Studies ; Cyclin-Dependent Kinase Inhibitor Proteins/*metabolism ; Humans ; Mesothelioma/*drug therapy/metabolism/pathology ; Pleural Neoplasms/*drug therapy/metabolism/pathology ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare and essentially incurable malignancy most often linked with occupational exposure to asbestos fibres. In common with other malignancies, the development and progression of MPM is associated with extensive dysregulation of cell cycle checkpoint proteins that modulate cell proliferation, apoptosis, DNA repair and senescence.

METHODS: The expression of cyclin-dependent kinase inhibitor p16/INK4A was evaluated by immunohistochemistry using tumour biopsy specimens from 88 MPM cases and a semi-quantitative score for p16/INK4A expression was obtained. Post-diagnosis survival and the survival benefit of chemotherapeutic intervention was correlated with p16/INK4A expression.

RESULTS: A low, intermediate and high score for p16/INK4A expression was observed for 45 (51.1%), 28 (31.8%) and 15 (17.1%) of the MPM cases, respectively. Those cases with intermediate or high p16/INK4A tumour expression had a significantly better post-diagnosis survival than those cases whose tumours lost p16 expression (log-rank P<0.001). Those patients with sustained p16/INK4A expression who received chemotherapy also had a better survival than those treated patients whose tumours had lost p16/INK4A expression (log-rank P<0.001).

CONCLUSIONS: Sustained p16/INK4A expression predicts better post-diagnosis survival in MPM and also better survival following chemotherapeutic intervention.}, } @article {pmid26052757, year = {2015}, author = {Hjerpe, A and Ascoli, V and Bedrossian, CW and Boon, ME and Creaney, J and Davidson, B and Dejmek, A and Dobra, K and Fassina, A and Field, A and Firat, P and Kamei, T and Kobayashi, T and Michael, CW and Önder, S and Segal, A and Vielh, P}, title = {Guidelines for the Cytopathologic Diagnosis of Epithelioid and Mixed-Type Malignant Mesothelioma: a secondary publication.}, journal = {Cytopathology : official journal of the British Society for Clinical Cytology}, volume = {26}, number = {3}, pages = {142-156}, doi = {10.1111/cyt.12250}, pmid = {26052757}, issn = {1365-2303}, mesh = {Cytodiagnosis ; Humans ; Mesothelioma/*diagnosis ; }, abstract = {OBJECTIVE: To provide practical guidelines for the cytopathologic diagnosis of malignant mesothelioma.

DATA SOURCES: Cytopathologists with an interest in the field involved in the International Mesothelioma Interest Group (IMIG) and the International Academy of Cytology (IAC) contributed to this update. Reference material includes peer-reviewed publications and textbooks.

RATIONALE: This article is the result of discussions during and after the IMIG 2012 conference in Boston, followed by thorough discussions during the 2013 IAC meeting in Paris. Additional contributions have been obtained from cytopathologists and scientists who could not attend these meetings, with final discussions and input during the IMIG 2014 conference in Cape Town.}, } @article {pmid26046696, year = {2016}, author = {Kawabata, Y and Shimizu, Y and Hoshi, E and Murai, K and Kanauchi, T and Kurashima, K and Sugita, Y}, title = {Asbestos exposure increases the incidence of histologically confirmed usual interstitial pneumonia.}, journal = {Histopathology}, volume = {68}, number = {3}, pages = {339-346}, doi = {10.1111/his.12751}, pmid = {26046696}, issn = {1365-2559}, mesh = {Aged ; Asbestos/*adverse effects ; Asbestosis/epidemiology/etiology/*pathology ; Female ; Humans ; Incidence ; Japan/epidemiology ; Lung Neoplasms/epidemiology/etiology/*pathology ; Male ; Mesothelioma/epidemiology/etiology/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Pleural Diseases/epidemiology/etiology/*pathology ; Pleural Neoplasms/epidemiology/etiology/*pathology ; Retrospective Studies ; Risk Factors ; }, abstract = {AIMS: We hypothesized that asbestos exposure increases the incidence of macroscopically visible and histologically confirmed usual interstitial pneumonia (histological UIP).

METHODS AND RESULTS: We retrospectively examined 1718 cases (1202 males; mean age 66.7 years) who underwent lobectomy for resection of pleuropulmonary tumours. Objective markers for asbestos exposure included: the presence of malignant pleural mesothelioma, the presence of pleural plaques (PPs) and asbestos bodies in the histological specimen. Risk factors for histological UIP were examined. Two separate groups were studied: 183 with asbestos exposure, and 239 with histological UIP. The 183 cases with asbestos exposure had higher rates of positive occupational history and histological UIP (31%) than the remaining 1535. Among the asbestos-exposed group, small numbers of asbestos bodies were found in histological specimens of 21 cases of histological UIP. PPs and asbestos bodies were more frequent in the 239 patients with histological UIP than in the remaining 1479 UIP-negative patients. Multivariate analysis showed that asbestos exposure, especially positivity for asbestos bodies, that does not meet the current criteria for asbestosis increases the risk of histological UIP (P < 0.0001).

CONCLUSIONS: Asbestos exposure causes asbestosis and increases the incidence of histological UIP.}, } @article {pmid26045315, year = {2015}, author = {Marinaccio, A and Binazzi, A and Bonafede, M and Corfiati, M and Di Marzio, D and Scarselli, A and Verardo, M and Mirabelli, D and Gennaro, V and Mensi, C and Schallemberg, G and Merler, E and Negro, C and Romanelli, A and Chellini, E and Silvestri, S and Cocchioni, M and Pascucci, C and Stracci, F and Ascoli, V and Trafficante, L and Angelillo, I and Musti, M and Cavone, D and Cauzillo, G and Tallarigo, F and Tumino, R and Melis, M and , }, title = {Malignant mesothelioma due to non-occupational asbestos exposure from the Italian national surveillance system (ReNaM): epidemiology and public health issues.}, journal = {Occupational and environmental medicine}, volume = {72}, number = {9}, pages = {648-655}, doi = {10.1136/oemed-2014-102297}, pmid = {26045315}, issn = {1470-7926}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Child ; Child, Preschool ; Environmental Exposure/*adverse effects ; Environmental Pollutants/*adverse effects ; Female ; Humans ; Incidence ; Infant ; Infant, Newborn ; Italy/epidemiology ; Lung Neoplasms/epidemiology/*etiology ; Male ; Mesothelioma/epidemiology/*etiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/adverse effects ; Pleural Neoplasms/epidemiology/*etiology ; Population Surveillance ; Public Health ; Sex Factors ; Young Adult ; }, abstract = {INTRODUCTION: Italy produced and imported a large amount of raw asbestos, up to the ban in 1992, with a peak in the period between 1976 and 1980 at about 160,000 tons/year. The National Register of Mesotheliomas (ReNaM, "Registro Nazionale dei Mesoteliomi" in Italian), a surveillance system of mesothelioma incidence, has been active since 2002, operating through a regional structure.

METHODS: The Operating Regional Center (COR) actively researches cases and defines asbestos exposure on the basis of national guidelines. Diagnostic, demographic and exposure characteristics of non-occupationally exposed cases are analysed and described with respect to occupationally exposed cases.

RESULTS: Standardised incidence rates for pleural mesothelioma in 2008 were 3.84 (per 100,000) for men and 1.45 for women, respectively. Among the 15,845 mesothelioma cases registered between 1993 and 2008, exposure to asbestos fibres was investigated for 12,065 individuals (76.1%), identifying 530 (4.4%) with familial exposure (they lived with an occupationally exposed cohabitant), 514 (4.3%) with environmental exposure to asbestos (they lived near sources of asbestos pollution and were never occupationally exposed) and 188 (1.6%) exposed through hobby-related or other leisure activities. Clusters of cases due to environmental exposure are mainly related to the presence of asbestos-cement industry plants (Casale Monferrato, Broni, Bari), to shipbuilding and repair activities (Monfalcone, Trieste, La Spezia, Genova) and soil contamination (Biancavilla in Sicily).

CONCLUSIONS: Asbestos pollution outside the workplace contributes significantly to the burden of asbestos-related diseases, suggesting the need to prevent exposures and to discuss how to deal with compensation rights for malignant mesothelioma cases induced by non-occupational exposure to asbestos.}, } @article {pmid26039812, year = {2015}, author = {Mesaros, C and Worth, AJ and Snyder, NW and Christofidou-Solomidou, M and Vachani, A and Albelda, SM and Blair, IA}, title = {Bioanalytical techniques for detecting biomarkers of response to human asbestos exposure.}, journal = {Bioanalysis}, volume = {7}, number = {9}, pages = {1157-1173}, pmid = {26039812}, issn = {1757-6199}, support = {T32 GM008076/GM/NIGMS NIH HHS/United States ; P42ES023720/ES/NIEHS NIH HHS/United States ; P30 ES013508/ES/NIEHS NIH HHS/United States ; P42 ES023720/ES/NIEHS NIH HHS/United States ; T32ES019851/ES/NIEHS NIH HHS/United States ; T32 ES019851/ES/NIEHS NIH HHS/United States ; P30ES013508/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Asbestos/*adverse effects ; Biomarkers/analysis ; Chemistry Techniques, Analytical/*methods ; Environmental Exposure/adverse effects/*analysis ; Humans ; Oxidative Stress/drug effects ; Pleura/drug effects/metabolism ; }, abstract = {Asbestos exposure is known to cause lung cancer and mesothelioma and its health and economic impacts have been well documented. The exceptionally long latency periods of most asbestos-related diseases have hampered preventative and precautionary steps thus far. We aimed to summarize the state of knowledge on biomarkers of response to asbestos exposure. Asbestos is not present in human biological fluids; rather it is inhaled and trapped in lung tissue. Biomarkers of response, which reflect a change in biologic function in response to asbestos exposure, are analyzed. Several classes of molecules have been studied and evaluated for their potential utility as biomarkers of asbestos exposure. These studies range from small molecule oxidative stress biomarkers to proteins involved in immune responses.}, } @article {pmid26024342, year = {2015}, author = {Markowitz, S}, title = {Asbestos-related lung cancer and malignant mesothelioma of the pleura: selected current issues.}, journal = {Seminars in respiratory and critical care medicine}, volume = {36}, number = {3}, pages = {334-346}, doi = {10.1055/s-0035-1549449}, pmid = {26024342}, issn = {1098-9048}, mesh = {Animals ; Asbestos/toxicity ; Asbestosis/complications/diagnosis ; Early Detection of Cancer ; Humans ; Lung Neoplasms/diagnosis/*etiology/pathology ; Mesothelioma/diagnosis/*etiology/pathology ; Mesothelioma, Malignant ; Occupational Diseases/diagnosis/etiology/pathology ; Occupational Exposure/adverse effects ; Pleural Neoplasms/diagnosis/*etiology/pathology ; Risk Assessment/methods ; Smoking/adverse effects ; Tomography, X-Ray Computed ; }, abstract = {Asbestos-related diseases persist, because millions of workers have had prior exposure and many industrializing countries continue to use asbestos. Globally, an estimated 107,000 people die annually from lung cancer, malignant mesothelioma, and asbestosis due to occupational asbestos exposure. Malignant mesothelioma and lung cancer are caused by all major types of asbestos. Asbestos causes more lung cancer deaths than malignant mesothelioma of the pleura; most cases of the latter are due to asbestos exposure. The cancer risk increases with cumulative asbestos exposure, with increased risk even at low levels of exposure to asbestos. Based on empirical studies, an estimated cumulative occupational exposure to asbestos of 1 fiber/mL-year substantially raises malignant mesothelioma risk. No safe threshold for asbestos exposure has been established for lung cancer and mesothelioma. The validity of fiber-type risk assessments depends critically on the quality of exposure assessments, which vary considerably, leading to a high degree of uncertainty. Asbestos exposure without asbestosis and smoking increases the risk of lung cancer. The joint effect of asbestos and smoking is supra-additive, which may depend in part on the presence of asbestosis. Asbestos workers who cease smoking experience a dramatic drop in lung cancer risk, which approaches that of nonsmokers after 30 years. Studies to date show that longer, thinner fibers have a stronger association with lung cancer than shorter, less thin fibers, but the latter nonetheless also show an association with lung cancer and mesothelioma. Low-dose chest computed tomographic scanning offers an unprecedented opportunity to detect early-stage lung cancers in asbestos-exposed workers.}, } @article {pmid26016578, year = {2015}, author = {Creaney, J and Dick, IM and Robinson, BW}, title = {Comparison of mesothelin and fibulin-3 in pleural fluid and serum as markers in malignant mesothelioma.}, journal = {Current opinion in pulmonary medicine}, volume = {21}, number = {4}, pages = {352-356}, doi = {10.1097/MCP.0000000000000167}, pmid = {26016578}, issn = {1531-6971}, mesh = {Biomarkers, Tumor ; Diagnosis, Differential ; Extracellular Matrix Proteins ; GPI-Linked Proteins ; Humans ; *Lung Neoplasms ; Mesothelin ; *Mesothelioma ; Mesothelioma, Malignant ; *Pleural Effusion/diagnosis ; }, abstract = {PURPOSE OF REVIEW: Malignant mesothelioma is an asbestos-induced, aggressive tumour, which frequently presents with pleural effusion. There are over 60 reported causes that can result in the development of a pleural effusion. Currently, there are no tumour biomarkers in widespread clinical use for the differential diagnosis of mesothelioma from other diseases. With the incidence of mesothelioma expected to continue to increase, it is timely to review the current status of effusion-based biomarkers for mesothelioma diagnosis.

RECENT FINDINGS: The majority of recent studies have evaluated soluble mesothelin in effusions in a diagnostic setting for mesothelioma. However, at high specificity, the sensitivity of the assay is limited to approximately 60% at the time of diagnosis. There is considerable research effort directed toward the identification of new markers for mesothelioma through a variety of genomic, proteomic and immunomic based platforms. One of the few new biomarkers to be identified through a biomarker discovery pipeline and evaluated in pleural effusions is fibulin-3. Preliminary results on the diagnostic accuracy of fibulin-3 have been inconsistent.

SUMMARY: To date, soluble mesothelin remains the best available biomarker for mesothelioma and a positive result is clinically useful in patients with pleural effusions in whom the diagnosis is uncertain.}, } @article {pmid27476317, year = {2015}, author = {Aubier, M}, title = {[Asbestos: An up-to-date general review].}, journal = {Bulletin de l'Academie nationale de medecine}, volume = {199}, number = {2-3}, pages = {383-389}, pmid = {27476317}, issn = {0001-4079}, mesh = {Asbestos/*adverse effects ; Asbestosis/*etiology ; Humans ; Occupational Exposure/*adverse effects ; }, abstract = {Major risks associated with asbestos exposure (mesothelioma, lung cancer and asbestosis) have been knownfor a long time. Various clinical and epidemiological studies, which include assessment of risk of developing cancer after discovering atypical computer-tomography (CT) images or pleural plaques in persons who had been exposed to asbestos, are still ongoing, however. This short report updates the risk of occupational exposure in 2014, the consequences of the former occupational exposures, the scale of compensation and recent legal dispositions intended to reduce the risk of occupational and non-professional exposure in France.}, } @article {pmid27476313, year = {2015}, author = {Chamoux, A}, title = {[Review and perspective of a long-term follow-up of two cohorts of workers heavily exposed to asbestos].}, journal = {Bulletin de l'Academie nationale de medecine}, volume = {199}, number = {2-3}, pages = {321-39; discussion 339-40}, pmid = {27476313}, issn = {0001-4079}, mesh = {Aged ; Asbestos/administration & dosage/*adverse effects ; Asbestosis/diagnosis/epidemiology/*etiology ; Cohort Studies ; Female ; Follow-Up Studies ; Humans ; Male ; Occupational Exposure/*adverse effects ; Time Factors ; }, abstract = {National screening programs for detection of breast, colon and cervical cancers have been set up in France. Occupational cancers are excluded from these programs. Surveillance is left to the initiative of former employees who can initiate post-professional medical monitoring. This study describes an experience of such monitoring organised by the health insurance in collaboration with "victims". The long term follow-up, every two years, of 324 workers directly and heavily exposed to asbestos confirms the high risk of developing lung cancer, mesothelioma or asbestosis, the latter at times rapidly evolving. The early discovery of 3 bronchopulmonary cancers points to the interest of an annual or biannual routine screening. While new imaging techniques reduce by a factor of 8 irradiation, without significantly affecting the diagnostic capacity, the health benefit provided by annual monitoring scanner in heavy smokers favors an early detection program for lung cancers. The population targeted for such a screening (active or former smoker with pleural plaques) should be defined in more detail. The increasingly frequent observation of lung or pleural changes besides the populations at risk should also be considered. Therefore the detecting procedures applied to those workers indirectly or discontinuously exposed should be reassessed (only 1 TDM at 60 y, or on retirement, for the relevant occupations). These data suggest that the recommendation HAS 2010 for post-professional screening of workers occupationally exposed to asbestos should be reconsidered, particularly in case of pleural plaques. An organized screening program needs to be overhauled.}, } @article {pmid27350803, year = {2015}, author = {Yasui, M and Kamoshita, N and Nishimura, T and Honma, M}, title = {Mechanism of induction of binucleated cells by multiwalled carbon nanotubes as revealed by live-cell imaging analysis.}, journal = {Genes and environment : the official journal of the Japanese Environmental Mutagen Society}, volume = {37}, number = {}, pages = {6}, pmid = {27350803}, issn = {1880-7046}, abstract = {INTRODUCTION: Asbestos-induced formation of mesothelioma has been attributed to phenotypic and morphological changes in cells caused by polyploidization and aneuploidization, and multiwalled carbon nanotubes (MWCNTs) are suspected to have similar adverse effects due to the similarity in their physical form. MWCNTs and crocidolite, a kind of asbestos, show similar genotoxicity characteristics in vitro, including induction of binucleated cells. We here focused on the mechanisms underlying polyploidization during cell division on exposure to MWCNTs and conducted confocal live-cell imaging analysis using MDA-435 human breast cancer cells in which chromosomes and centromeres were visualized using fluorescent proteins.

FINDINGS: During anaphase, relatively short MWCNT fibers (approximately 5 μm) migrated rapidly to either of the daughter cells, whereas some long MWCNT fibers (approximately 20 μm) remained inside the contractile ring and induced the formation of binucleated cells through impairment of cytokinesis. This toxicity mechanism has also been observed with crocidolite.

CONCLUSIONS: Our findings indicate that the mechanism of polyploidization by MWCNTs is very similar to that observed with crocidolite.}, } @article {pmid28548074, year = {2014}, author = {Gaudino, G and Yang, H and Carbone, M}, title = {HGF/Met Signaling Is a Key Player in Malignant Mesothelioma Carcinogenesis.}, journal = {Biomedicines}, volume = {2}, number = {4}, pages = {327-344}, pmid = {28548074}, issn = {2227-9059}, abstract = {Malignant mesothelioma (MM) is a highly aggressive cancer related to asbestos or erionite exposure and resistant to current therapies. Hepatocyte Growth Factor (HGF) and its tyrosine kinase receptor Met regulate cell growth, survival, motility/migration, and invasion. HGF and Met are expressed in MM cells, suggesting that the HGF/Met signaling plays a role in development and progression of this tumor, by autocrine and/or paracrine mechanisms. Upregulation and ligand-independent activation of Met, which is under suppressive control of miR-34 family members, correlate with enhanced invasion, migration and metastatic potential in several cancers, including MM. Moreover, Simian Virus 40 (SV40) Tag expression also induces a HGF autocrine circuit in an Rb-dependent manner in human mesothelial cells (HM) and possibly other cell types, enhancing cell adhesion, invasion and angiogenesis. The resulting activation of Met causes HM transformation and cell cycle progression, and contributes to virus particle assembling and infection of adjacent cells. The constitutive activation of Met, frequently occurring in MM, has been successfully targeted in preclinical models of MM. In conclusion, Met expression, activation state, subcellular localization and also HGF co-receptors expression, such as CD44, have clinical relevance for novel targeted therapies in a cancer for which no effective treatment is currently available.}, } @article {pmid28652992, year = {2014}, author = {da Fonseca, LG and Marques, DF and Takahashi, TK and Aguiar, FN and Ravanini, JN and Saragiotto, DF}, title = {Malignant paratesticular mesothelioma.}, journal = {Autopsy & case reports}, volume = {4}, number = {1}, pages = {45-51}, pmid = {28652992}, issn = {2236-1960}, abstract = {Mesothelioma of the tunica vaginalis testis (MTVT) is a rare tumor that usually affects patients after the sixth decade of life. Exposure to asbestos is a known risk factor. Enlargement of the scrotal volume is the most common initial clinical manifestation, and about 15% of cases present metastasis at diagnosis. The treatment relies on surgical resection while the role of adjuvant chemotherapy and radiotherapy remains unclear. The prognosis for patients is generally poor, with a lethal outcome in 30% over a 24-month period. The authors report a case of a 62-year-old patient with the diagnosis of MTVT without a history of asbestos exposure. After surgical treatment, metastatic disease ensued. Chemotherapy was initiated, but could not be continued due to marked and fast clinical deterioration. The authors call attention to the difficulty of early diagnosis of MTVT due to a nonspecific clinical picture, the lack of action by the patient when the scrotal enlargement was first noticed, and the lack of tumor markers. Delayed diagnosis is definitely related to unfavorable prognosis.}, } @article {pmid26766976, year = {2014}, author = {Kohno, M and Maruyama, R and Kitagawa, D and Sugimachi, K and Kinjo, M and Higashi, H}, title = {Localized biphasic type malignant mesothelioma arising in the peritoneum: Report of a case.}, journal = {Thoracic cancer}, volume = {5}, number = {1}, pages = {74-77}, pmid = {26766976}, issn = {1759-7706}, abstract = {This report describes a rare case of localized malignant biphasic (mixed epithelioid and sarcomatoid) mesothelioma arising in the peritoneum. A 69-year-old male with a history of asbestos exposure, complaining of a painful mass in the left chest wall, was found via computed tomography (CT) to have a tumor in the left peritoneum. The resected tumor was histologically and immunohistochemically consistent with a malignant mesothelioma with mixed epithelioid and sarcomatoid type and no distant metastasis. The diagnosis of localized malignant biphasic mesothelioma arising in the peritoneum was appropriate because there was no evidence of any other primary tumor.}, } @article {pmid26742297, year = {2014}, author = {Espinosa, CR and Rivera, LM and Rangell, TE}, title = {[Malignant peritoneal mesothelioma in patients without occupational exposure. Case report].}, journal = {Acta gastroenterologica Latinoamericana}, volume = {44}, number = {3}, pages = {243-245}, pmid = {26742297}, issn = {0300-9033}, mesh = {Asbestos ; Biopsy ; Humans ; Male ; Mesothelioma/*pathology ; Middle Aged ; *Occupational Exposure ; Paracentesis ; Peritoneal Neoplasms/*pathology ; Risk Factors ; }, abstract = {Peritoneal mesothelioma is a rare malignancy that affects more women than men, with an average of 53 years old. The most important risk factor for developing the disease is chronic exposure to asbestos, becoming a disease of occupational origin. This type of cancer is difficult to diagnose, even for pathologists, with few cases reported in the literature as the most common presentation is the pleural type. We report the case of a male patient, without asbestos exposure, who presented malignantperitoneal mesothelioma.}, } @article {pmid26029551, year = {2014}, author = {Tertemiz, KC and Ozgen Alpaydin, A and Gurel, D and Savas, R and Gulcu, A and Akkoclu, A}, title = {Multiple distant metastases in a case of malignant pleural mesothelioma.}, journal = {Respiratory medicine case reports}, volume = {13}, number = {}, pages = {16-18}, pmid = {26029551}, issn = {2213-0071}, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is a malignant of mesodermal neoplasm and arises from multipotential mesothelial or subserosal cells of the pleura, pericardium and peritoneum.

CASE: A seventy five year-old male patient was admitted with chest and lower limb pain. He was a heavy smoker and exposed to environmental asbestos in his childhood. PET-CT scans showed multiple pathological FDG uptakes in lungs and other organs. Biopsies performed from lung and anterior thigh muscles were reported as epitheloid type malignant pleural mesothelioma.

DISCUSSION: We emphasize that unexpected distant metastases can be observed in MPM and occasionally primary diagnosis can be determined by the biopsy of the metastatic regions. This case also points out the role of PET-CT in the staging of malign mesothelioma by determining different metastatic sites.}, } @article {pmid27158561, year = {2013}, author = {Kim, SJ and Williams, D and Cheresh, P and Kamp, DW}, title = {Asbestos-Induced Gastrointestinal Cancer: An Update.}, journal = {Journal of gastrointestinal & digestive system}, volume = {3}, number = {3}, pages = {}, pmid = {27158561}, issn = {2161-069X}, support = {I01 BX000786/BX/BLRD VA/United States ; R01 ES020357/ES/NIEHS NIH HHS/United States ; }, abstract = {Asbestos-related diseases, such as malignancies and asbestosis, remain a significant occupational and public health concern. Asbestos is still widely used in many developing countries despite being a recognized carcinogen that has been banned over 50 countries. The prevalence and mortality from asbestos-related diseases continue to pose challenges worldwide. Many countries are now experiencing an epidemic of asbestos-related disease that is the legacy of occupational exposure during the 20th century because of the long latency period (up to 40 years) between initial asbestos exposure and exhibition of disease. However, the gastrointestinal (GI) cancers resulting from asbestos exposure are not as clearly defined. In this review, we summarize some of the recent epidemiology of asbestos-related diseases and then focus on the evidence implicating asbestos in causing GI malignancies. We also briefly review the important new pathogenic information that has emerged over the past several years that may account for asbestos-related gastrointestinal cancers. All types of asbestos fibers have been implicated in the mortality and morbidity from GI malignancies but the collective evidence to date is mixed. Although the molecular basis of GI cancers arising from asbestos exposure is unclear, there have been significant advances in our understanding of mesothelioma and asbestosis that may contribute to the pathophysiology underlying asbestos-induced GI cancers. The emerging new evidence into the pathogenesis of asbestos toxicity is providing insights into the molecular basis for developing novel therapeutic strategies for asbestos-related diseases in future management.}, } @article {pmid28920322, year = {2013}, author = {Okamoto, T and Yano, T and Haro, A and Yoshida, T and Kohno, M and Maehara, Y}, title = {Treatment for recurrence after extrapleural pneumonectomy for malignant pleural mesothelioma: A single institution experience.}, journal = {Thoracic cancer}, volume = {4}, number = {1}, pages = {66-70}, doi = {10.1111/j.1759-7714.2012.00138.x}, pmid = {28920322}, issn = {1759-7714}, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a relatively rare, aggressive neoplasm associated with asbestos exposure. Extrapleural pneumonectomy (EPP) is often performed for resectable MPM as part of a multidisciplinary treatment; however, available data on treatments for recurrence after EPP are limited.

METHODS:   The clinical records of consecutive MPM patients who underwent EPP at our institution from 2001 to 2010 were retrospectively reviewed. There were 10 patients who underwent EPP with or without perioperative chemotherapy; of these, recurrence was observed in eight patients.

RESULTS:   The overall median survival time and time to recurrence were 49.6 months and 15.4 months, respectively, after EPP. The first recurrence occurred within the ipsilateral thorax in four patients. These patients all underwent local treatments for their recurrence, including surgery or radiotherapy and with or without systemic chemotherapy. Other first recurrences were seen in the peritoneal space of two patients and in the contralateral lung of two patients. These patients received platinum-based systemic chemotherapy for their recurrence. The median survival time after the first recurrence was 17.8 months, and the 2-year survival rate was 23.4%.

CONCLUSIONS:   Most patients who underwent EPP developed tumor recurrences. Direct tumor extension may be a major mechanism of recurrence. Aggressive treatment for recurrent MPM after EPP, including locoregional control and/or systemic chemotherapy, was important for achieving long-term survival.}, } @article {pmid28920270, year = {2012}, author = {Ambrogi, V and Mineo, TC and , }, title = {Clinical and biologic prognostic factors in malignant pleural mesothelioma.}, journal = {Thoracic cancer}, volume = {3}, number = {4}, pages = {289-302}, doi = {10.1111/j.1759-7714.2012.00127.x}, pmid = {28920270}, issn = {1759-7714}, abstract = {Malignant pleural mesothelioma is an extremely aggressive neoplasm of the pleura mainly attributable to asbestos exposure. Conventional medical, physical, and surgical treatments and their combinations are basically ineffective and just a few subjects experience some benefit. No definite guidelines can be provided in patient selection and therapeutic strategies. Currently, malignant pleural mesothelioma therapy is guided by clinical stage and patient characteristics, which are quite unreliable, rather than by the histological or molecular features of the tumor. In the present review the impact on prognosis of classic (i.e. etiology, age, gender, histology, staging), as well as relatively new clinical factors such as quality of life, positron emission tomography assessment, and occult residual disease, are firstly evaluated. In the second section of the review several biological variables and genetic markers, which have been recently recognized as the bases of the disease onset and development, are listed and discussed. There are serum and tissue markers. The latter are mainly related to cell cycle regulation, apoptosis, and growth factor pathways. These novel factors may play an important role in defining the prognosis of the disease and, subsequently, may have a place in addressing therapy.}, } @article {pmid27755841, year = {2011}, author = {Adel, AM and Abdel Hafeez, ZM and El Sheikh, ET and El Sharawy, IA and Gobran, NS}, title = {Malignant pleural mesothelioma: A retrospective analysis of clinicopathological and survival data.}, journal = {Thoracic cancer}, volume = {2}, number = {1}, pages = {16-23}, doi = {10.1111/j.1759-7714.2010.00033.x}, pmid = {27755841}, issn = {1759-7714}, abstract = {BACKGROUND: The aim of this study was to analyze the clinicopathological features of malignant pleural mesothelioma (MPM) and evaluate the therapeutic measures offered to patients with MPM and their impact on survival.

METHODS:   Data was retrospectively collected from the medical records of 304 patients who presented to the Department of Clinical Oncology and Nuclear Medicine, Ain Shams University between January 2003 and December 2008.

RESULTS:   The mean age of patients was 52.1 years (range 24-87 years). One hundred and ninety patients (62.5%) came from endemic areas and/or gave history of occupational asbestos exposure. One hundred and sixty-nine patients received chemotherapy. There was a significant difference between the median survival for patients who received chemotherapy (9 months, 95% CI 7.69-10.30) and those who were offered best supportive care (2 months, 95% CI 0.09-3.91). Other factors that affected the survival negatively were: non-epithelial pathology (P= 0.001); age >50 years (P= 0.012); bad performance status (P= 0.001); non-platinum based chemotherapy (P= 0.0001); and progressive disease (P= 0.000). Cox regression analysis revealed that the factors that predicted shorter survival were patients being offered best supportive care rather than chemotherapy and progressive disease.

CONCLUSION:   MPM is a growing health problem in Egypt that needs more attention. The current analysis of data reflects the importance of maintaining a high index of suspicion to allow for early diagnosis, especially for cases that live in areas with high asbestos exposure and for people who work in occupations that expose them to asbestos as well as their family members. Prospective randomized trials comparing multimodality approaches to other forms of treatment and including quality of life assessment are warranted.}, } @article {pmid27755778, year = {2010}, author = {Hürmüz, P}, title = {Management of malignant pleural mesothelioma.}, journal = {Thoracic cancer}, volume = {1}, number = {2}, pages = {53-61}, doi = {10.1111/j.1759-7714.2010.00001.x}, pmid = {27755778}, issn = {1759-7714}, abstract = {Malignant pleural mesothelioma is a rare neoplasm arising from the surface serosal cells of the pleural cavity. More than 80% of cases of malignant pleural mesothelioma have been attributed to asbestos exposure. In its natural course median survival is 4 to 12 months. If untreated most of patients die due to local complications of the disease. Surgery improves local control but is not sufficient as a single treatment modality. The recommended treatment strategy for a select group of patients is multimodal therapy that includes surgery, radiotherapy and chemotherapy.}, } @article {pmid26839029, year = {2010}, author = {Attanoos, RL}, title = {Asbestos-Related Lung Disease.}, journal = {Surgical pathology clinics}, volume = {3}, number = {1}, pages = {109-127}, doi = {10.1016/j.path.2010.04.003}, pmid = {26839029}, issn = {1875-9181}, abstract = {Asbestos is a high-profile health hazard. This article examines the assessment asbestos-related malignant mesothelioma and lung cancer. The risk of developing these diseases increases in proportion to the cumulative dose. As persons with heavy occupational asbestos exposures are diminishing, the observed latent period for asbestos-related disease extends making the assessment of an individual's cumulative dose is now more problematic.}, } @article {pmid31394644, year = {2005}, author = {Mohr, S and Neuville, A and Bottin, MC and Micillino, JC and Keith, G and Rihn, BH}, title = {Immune Signature of Malignant Pleural Mesothelioma as Assessed by Transcriptome Analysis.}, journal = {Cancer genomics & proteomics}, volume = {2}, number = {3}, pages = {125-135}, pmid = {31394644}, issn = {1790-6245}, abstract = {Malignant pleural mesothelioma (MPM) is a highly malignant tumor arising in patients previously exposed to asbestos fibers. Its increasing incidence and its social, financial and human impact have become a frequent problem in many industrialized countries. The unresponsiveness of malignant mesothelioma to conventional therapies has led clinicians to develop new treatments. As immunotherapy has been shown to offer promising and targeted treatment of MPM patients, the knowledge of the immunoresistance level of MPM may be a valuable tool for "à la carte" therapy. In a previous work, we profiled the gene expression of two MPM tissues compared to healthy mesothelial cells using a 10K cDNA microarray. Subsequent clustering analysis identified several clusters of differentially-expressed genes among those that are functionally-related to the immune system. In this report, we focus on genes with expression changes that may facilitate tumor escape from immune-mediated rejection. We also analyzed the immune reaction by staining the immunocompetent cells surrounding the tumor. Interestingly, the tumor with the strongest escape response, as shown by the expression of numerous immunoresistance-associated genes, displayed the strongest T cell infiltrate. The main genes conferring immunoresistance are CD74, HLADOA, HLADMB, PTGS1, IGFBP7 and TGFB3, by favoring immune tolerance, and CFLAR, DFFA, TNFRSF6, BNIP3L by impairing apoptosis. These observations have fundamental consequences in the understanding of immunological properties of MPM, and offer a new insight into the mechanisms whereby MPM may circumvent host-mediated immune activities and promotes its own development. For an immunomodulation strategy to cure mesothelioma, it is crucial to characterize the MPM "immune signature" to design adapted immunotherapies.}, } @article {pmid26368633, year = {2000}, author = {Sandhu, H and Olbrück, H and Abel, J and Unfried, K}, title = {Differential Display Analysis of Fiber-Induced Carcinogenesis in Rat: Clue for Involvement of Integrin-Mediated Signal Transduction.}, journal = {Inhalation toxicology}, volume = {12 Suppl 3}, number = {}, pages = {337-343}, doi = {10.1080/08958378.2000.11463243}, pmid = {26368633}, issn = {0895-8378}, abstract = {In this study, mRNA expression patterns during mesothelioma carcinogenesis in the peritoneal cavity were investigated. To this purpose, the mRNA expression patterns of fiber-induced mesothelioma and of fiber-treated tissues were compared to untreated tissues, respectively. Suppression subtractive hybridization (SSH) and an array hybridization assay were used to perform differential display analyses. Genes found to be expressed differentially mainly represent proteins of signal transduction pathways and regulatory proteins of the cell cycle. The genes for components of the AP-1 transcription factor, c-jun, c-fos, and fra-1 (fos-related antigen-1) are upregulated in nontumorous tissue treated with asbestos. These data confirm in vivo the involvement of AP-I expression as response to fiber treatment. In addition, osteopontin, zyxin, and integrin-linked kinase were upregulated in tumors and in treated tissues. These genes code for proteins involved in the signal transduction from the extracellular matrix to the nucleus. Using integrin-specific inhibitors, the apoptotic effects of crocidolite fibers could be suppressed significantly. From these results we hypothesize that direct effects of the fibers on the target tissue are mediated by interaction of the fibers with the extracellular matrix molecules.}, } @article {pmid26368632, year = {2000}, author = {Faux, SP and Houghton, CE}, title = {Cell Signaling in Mesothelial Cells by Asbestos: Evidence for the Involvement of Oxidative Stress in the Regulation of the Epidermal Growth Factor Receptor.}, journal = {Inhalation toxicology}, volume = {12 Suppl 3}, number = {}, pages = {327-336}, doi = {10.1080/08958378.2000.11463242}, pmid = {26368632}, issn = {0895-8378}, abstract = {Asbestos has been shown to stimulate the mitogen-activated protein kinase signaling cascade after autophosphoryiation of the epidermal growth factor recptor (EGF-R), an event important in regulating the response of cells to extracellular signals. In studies reported here, we have examined whether mineral fibers with known carcinogenicity can be discriminated from nonpathogenic fibers by their ability to upregulate expression of EGF-R protein in mesothelial cells. Crocidolite and erionite, two fibrous preparations known to induce mesothelioma, increased expression of EGF-R protein in a time- and dose-dependent manner, whereas milled (nonfibrous) crocidolite and chrysotile asbestos, two preparations with much less or no ability to induce mesothelioma, did not. Intense patterns of EGF-R protein expression were linked to mesothelial cells phagocytosing long fibers as observed by phase-contrast microscopy. To determine the importance of EGF-R expression in these cells, we assessed downstream signaling events in rat pleural mesothelial (RPM) cells by looking at the induction of activator protein-1 (AP-I), a transcription factor that controls the transition to S phase in the cell cycle, leading to cell proliferation. Crocidolite induced AP-I in RPM cells in a dose-dependent manner, and this induction of AP-I in RPM cells was inhibited by coincubation with tyrphostin AG 1478, a potent inhibitor of the EGF-R. To examine the mechanism of induction of EGF-R in RPM cells by asbestos, RPM cells were treated with crocidolite in the presence and absence of the antioxidant N-acetylcysteine (NAC). Reduced glutathione (GSH) was examined as a marker of oxidative stress and the expression of EGF-R protein was measured. Crocidolite asbestos caused a dose-dependent depletion of GSH in RPM cells, and the presence of NAC ameliorated the expression of EGF-R protein by crocidolite. Our data suggest that carcinogenic fibers induce EGF-R via a mechanism involving oxidative stress initiating cell signaling cascades in mesothelial cells leading to cell proliferation and carcinogenesis.}, } @article {pmid26368614, year = {2000}, author = {McConnell, EE and Carbone, M}, title = {A Comparison of Pleural Mesotheliomas Induced by Asbestos or SV40 Virus in Syrian Golden Hamsters.}, journal = {Inhalation toxicology}, volume = {12 Suppl 3}, number = {}, pages = {173-181}, doi = {10.1080/08958378.2000.11463211}, pmid = {26368614}, issn = {0895-8378}, abstract = {Pleural mesotheliomas are a well-known consequence of exposure to asbestos in both humans and animals. However, there are cases of mesothelioma in humans for which there is little or no known exposure to asbestos. Mesotheliomas have also been produced in hamsters infected with simian virus 40 (SV40), a contaminant of early polio vaccines, which was shown to replicate in individuals inoculated with the vaccine. Recently, wild-type SV40 has been detected in human mesotheliomas as well as other types of neoplasms. Because the tumors were induced with such dissimilar agents, we evaluated mesotheliomas produced in hamsters after intrapleural injection of SV40 compared to those produced after inhalation exposure to amosite asbestos to see if there were differences in the development and morphology of the tumors. Although the mesotheliomas produced by both agents were clearly of mesothelial origin based on standard morphological criteria, there were clear differences. The SV40-induced tumors occurred with a short latency period, were large multicentric lesions with pleural effusion that always caused death within 3 to 6 mo, and were largely composed of small round cells growing in a uniformly tubulopapillary pattern with many areas of sarcomatous change. They had a minimal amount of stroma and tended to invade the adjacent tissues. The unaffected pleura showed no evidence of fibrosis. In contrast, the mesotheliomas induced by asbestos occurred much later (most after 18 mo), were rarely (<10%) the cause of death, and were typically very small with little evidence of pleural effusion. While they also had a tubulopapillary pattern, they were composed of larger cells with more abundant cytoplasm and sarcomatous change was rare. The adjacent pleura typically showed marked evidence of fibrosis and local invasion was rarely encountered. Whether these striking morphological differences between SV40- and asbestos-induced mesotheliomas in hamsters have a correlate in humans is not known. It would be useful to conduct a similar comparison of mesotheliomas from humans known to have been exposed to high levels of asbestos to those with no known exposure to see if similar morphological differences exist.}, } @article {pmid26368611, year = {2000}, author = {Unfried, K and Sandhu, H and Schürkes, C and Albrecht, C and Abel, J}, title = {Effects of Crocidolite Fibers on the Peritoneal Mesothelium of Rats.}, journal = {Inhalation toxicology}, volume = {12 Suppl 3}, number = {}, pages = {149-155}, doi = {10.1080/08958378.2000.11463208}, pmid = {26368611}, issn = {0895-8378}, abstract = {The assay of intraperitoneal (ip) injection to rats was used as experimental system to study the mechanisms of carcinogenic effects of fibrous dusts. With this test system, fibers were shown to induce mesothelioma in the peritoneal cavity. Although the data of the ip assay are discussed controversially in terms of risk assessment, it is a valuable tool to investigate the molecular mechanisms of mesothelioma carcinogenesis in vivo. This test system allows one to investigate both the effects of fibers on signal transduction and the genotoxic potential of fibers. On the level of mRNA expression, different stages of fiber-induced tumor development in the peritoneal space were examined using differential display techniques. Genes of signal transduction pathways are mainly affected by the fiber treatment; for example, the activation of genes for the AP-1 transcription factor could be observed in the tissues of the peritoneal cavity. Thus, our in vivo data confirm the findings reported from cell culture systems. Moreover, our results from the differential display assays reveal that genes involved in the integrin-linked signal transduction are upregulated. In addition, the ip assay can be applied to transgenic animals to perform mutagenicity testing. Using the Big Blue transgenic animal system, we provide data of a significant increase in mutation frequency after treatment with crocidolite asbestos.}, } @article {pmid26368610, year = {2000}, author = {Hei, TK and Xu, A and Louie, D and Zhao, YL}, title = {Genotoxicity Versus Carcinogenicity: Implications from Fiber Toxicity Studies.}, journal = {Inhalation toxicology}, volume = {12 Suppl 3}, number = {}, pages = {141-147}, doi = {10.1080/08958378.2000.11463207}, pmid = {26368610}, issn = {0895-8378}, abstract = {Although the association between exposure to asbestos fibers and the development of lung cancer and mesothelioma has been well established in humans, the carcinogenic potential of other natural and man-made fibers/particles is not clear. Various in vitro genotoxicity studies have been employed to assess their in vivo carcinogenic potential. Studies using mammalian cell models have suggested that fiber dimensions, surface properties, physical durability, and cell and tissue responses are important criteria for the carcinogenicity of the fibers. Studies using oncogenic transformation as an endpoint have shown that asbestos fibers can induce malignantly transformed foci in certain rodent cells and that oxygen radicals are important in the toxic, oncogenic transforming, and mutagenic effects of asbestos fibers. The mutagenicity of asbestos in mammalian cells have been demonstrated using several model systems that can detect large multilocus deletions. These findings provide a direct link between chromosomal abnormalities that have frequently been demonstrated in fiber-exposed human and rodent cell lines and carcinogenicity in vivo. Although asbestos has not been shown to malignantly transform primary human epithelial cells, it can induce neoplastic conversion of immortalized human bronchial epithelial cells in a stepwise fashion and provides a unique opportunity to assess the molecular alterations associated with each stage of the neoplastic process.}, } @article {pmid26368609, year = {2000}, author = {Kane, AB}, title = {Oncogenes and Tumor Suppressor Genes in the Carcinogenicity of Fibers and Particles.}, journal = {Inhalation toxicology}, volume = {12 Suppl 3}, number = {}, pages = {133-140}, doi = {10.1080/08958378.2000.11463206}, pmid = {26368609}, issn = {0895-8378}, abstract = {Asbestos fibers and crystalline silica are carcinogenic to humans when inhaled into the lungs. Asbestos fibers and cigarette smoke most likely act as cofactors in the induction of lung cancer. Point mutations in the K-ras oncogene and the p53 tumor-suppressor gene are frequent in lung cancers and are consistent with the known mutagenic spectrum of tobacco-smoke carcinogens. The FHIT tumor suppressor gene is also frequently inactivated in lung cancers of smokers and in workers who were exposed to asbestos. Recent molecular studies of p53 tumor suppressor gene mutations and p53 protein expression in the lungs of patients with lung cancer and occupational exposure to crystalline silica and other dusts have been conducted. Mutations in the p53 gene were detected at a frequency similar to those in smoking-related lung cancers. Expression of p53 protein can be detected by immunohisto-chemistry in preneoplastic epithelial lesions in the lungs of smokers and workers. Human malignant mesotheliomas frequently show overexpression of p53 protein; however, point mutations at the p53 tumor suppressor gene or ras oncogene locus are rare. Most cases of malignant mesotheliomas have codeletions of the p15 and p16 tumor suppressor genes and alterations at the NF2 tumor suppressor gene locus with monosomy of chromosome 22. The molecular alterations characteristic of malignant mesotheliomas may develop during later stages of tumor progression and may not reflect the direct genotoxic effects of fibers on the target cell population.}, } @article {pmid26016040, year = {2015}, author = {Szeszenia-Dąbrowska, N and Świątkowska, B and Sobala, W and Szubert, Z and Wilczyńska, U}, title = {Asbestos related diseases among workers of asbestos processing plants in relation to type of production and asbestos use.}, journal = {Medycyna pracy}, volume = {66}, number = {1}, pages = {1-9}, pmid = {26016040}, issn = {0465-5893}, mesh = {Aged ; Asbestosis/diagnosis/*epidemiology ; Female ; Humans ; Lung Neoplasms/diagnosis/*epidemiology ; Male ; Mass Screening/*statistics & numerical data ; Middle Aged ; National Health Programs/organization & administration ; Occupational Diseases/diagnosis/*epidemiology ; Occupational Exposure/*statistics & numerical data ; Occupations/*statistics & numerical data ; Poland/epidemiology ; Population Surveillance ; Public Health ; Retrospective Studies ; Risk Factors ; }, abstract = {BACKGROUND: Asbestos dust is one of the most dangerous pneumoconiotic and carcinogenic agents. The aim of this study was to assess the occurrence of asbestosis and pleural mesothelioma, depending on asbestos consumption and the type of manufactured products, among former asbestos workers in Poland.

MATERIAL AND METHODS: The study subjects included employees of 18 large state-owned asbestos processing enterprises operating in the Polish market in 1945-1998. The study is based on data obtained from asbestos company records and the Central Register of Occupational Diseases data on the cases of asbestosis and mesothelioma for the period from 1970 till 2012 as well as data from Amiantus Programme. The analysis was performed for 5 sectors comprising plants classified according to the products manufactured and applied production technology.

RESULTS: In the study period, 2160 cases of asbestosis and 138 cases of mesothelioma were reported. The plants processed a total of about 2 million tons of asbestos, including about 7.5% of crocidolite. Total asbestosis consumption was a strong predictor of the rate of asbestosis incidence (R2 = 0.68, p = 0.055). The highest risk occurrence of asbestosis was observed in the production of textiles and sealing products. Mesothelioma occurred only in plants where crocidolite had been ever processed.

CONCLUSIONS: Total asbestos consumption was a strong predictor of the rate of asbestosis incidence. The observation confirms the relationship between exposure to crocidolite and the occurrence of mesothelioma, regardless of the manufactured products, and suggests the absence of such a link for the total volume of asbestos consumption.}, } @article {pmid26011325, year = {2015}, author = {Hountis, P and Chounti, M and Matthaios, D and Romanidis, K and Moraitis, S}, title = {Surgical treatment for malignant pleural mesothelioma: extrapleural pneumonectomy, pleurectomy/decortication or extended pleurectomy?.}, journal = {Journal of B.U.ON. : official journal of the Balkan Union of Oncology}, volume = {20}, number = {2}, pages = {376-380}, pmid = {26011325}, issn = {1107-0625}, mesh = {Humans ; Lung Neoplasms/*surgery ; Mesothelioma/*surgery ; Mesothelioma, Malignant ; Pleura/*surgery ; Pleural Neoplasms/*surgery ; Pneumonectomy/*methods ; }, abstract = {Malignant pleural mesothelioma (MPM) is an asbestos-related disease with a dismal prognosis. Ethic, social, legal and economic parameters are implicated in its management. It is quite clear that multimodality therapy is necessary to improve long-term results but precise treatment schemes have not yet been equivocally accepted. The extent of surgery is questioned and radical operations are highly debatable. On the other hand, debulking or cyto-reductive surgery have been also proposed within a multimodality approach. However, the role and order of adjuvant or neoadjuvant use of chemotherapy, radiotherapy and surgery has not been established. The aim of this study was to analyze contemporary studies on the impact of different surgical approaches on outcome of patients with MPM.}, } @article {pmid25985714, year = {2015}, author = {Cowan, DM and Cheng, TJ and Ground, M and Sahmel, J and Varughese, A and Madl, AK}, title = {Analysis of workplace compliance measurements of asbestos by the U.S. Occupational Safety and Health Administration (1984-2011).}, journal = {Regulatory toxicology and pharmacology : RTP}, volume = {72}, number = {3}, pages = {615-629}, doi = {10.1016/j.yrtph.2015.05.002}, pmid = {25985714}, issn = {1096-0295}, mesh = {Agriculture ; Air Pollutants, Occupational/*analysis/history/standards ; Asbestos/*analysis/history/standards ; Databases, Factual ; Environmental Monitoring ; History, 20th Century ; History, 21st Century ; Industry ; Occupational Exposure/*analysis/history/standards ; Transportation ; United States ; United States Occupational Safety and Health Administration/*standards ; Workplace/*standards ; }, abstract = {The United States Occupational Safety and Health Administration (OSHA) maintains the Chemical Exposure Health Data (CEHD) and the Integrated Management Information System (IMIS) databases, which contain quantitative and qualitative data resulting from compliance inspections conducted from 1984 to 2011. This analysis aimed to evaluate trends in workplace asbestos concentrations over time and across industries by combining the samples from these two databases. From 1984 to 2011, personal air samples ranged from 0.001 to 175 f/cc. Asbestos compliance sampling data associated with the construction, automotive repair, manufacturing, and chemical/petroleum/rubber industries included measurements in excess of 10 f/cc, and were above the permissible exposure limit from 2001 to 2011. The utility of combining the databases was limited by the completeness and accuracy of the data recorded. In this analysis, 40% of the data overlapped between the two databases. Other limitations included sampling bias associated with compliance sampling and errors occurring from user-entered data. A clear decreasing trend in both airborne fiber concentrations and the numbers of asbestos samples collected parallels historically decreasing trends in the consumption of asbestos, and declining mesothelioma incidence rates. Although air sampling data indicated that airborne fiber exposure potential was high (>10 f/cc for short and long-term samples) in some industries (e.g., construction, manufacturing), airborne concentrations have significantly declined over the past 30 years. Recommendations for improving the existing exposure OSHA databases are provided.}, } @article {pmid25979846, year = {2015}, author = {Panou, V and Vyberg, M and Weinreich, UM and Meristoudis, C and Falkmer, UG and Røe, OD}, title = {The established and future biomarkers of malignant pleural mesothelioma.}, journal = {Cancer treatment reviews}, volume = {41}, number = {6}, pages = {486-495}, doi = {10.1016/j.ctrv.2015.05.001}, pmid = {25979846}, issn = {1532-1967}, mesh = {Biomarkers, Tumor/*analysis ; Calbindin 2/analysis ; Extracellular Matrix Proteins/analysis ; Humans ; Hyaluronic Acid/analysis ; Immunohistochemistry ; Keratin-5/analysis ; Lung Neoplasms/*diagnosis ; Membrane Glycoproteins/analysis ; Mesothelioma/*diagnosis ; Mesothelioma, Malignant ; MicroRNAs/analysis ; Pleural Neoplasms/*diagnosis ; Tumor Suppressor Proteins/genetics ; Ubiquitin Thiolesterase/genetics ; WT1 Proteins/analysis ; }, abstract = {Malignant pleural mesothelioma (MPM) is an asbestos-related cancer with a median survival of 12months. The MPM incidence is 1-6/100,000 and is increasing as a result of historic asbestos exposure in industrialized countries and continued use of asbestos in developing countries. Lack of accurate biomarkers makes diagnosis, prognostication and treatment prediction of MPM challenging. The aim of this review is to identify the front line of MPM biomarkers with current or potential clinical impact. Literature search using the PubMed and PLoS One databases, the related-articles function of PubMed and the reference lists of associated publications until April 26th 2015 revealed a plethora of candidate biomarkers. The current gold standard of MPM diagnosis is a combination of two positive and two negative immunohistochemical markers in the epithelioid and biphasic type, but sarcomatous type do not have specific markers, making diagnosis more difficult. Mesothelin in serum and pleural fluid may serve as adjuvant diagnostic with high specificity but low sensitivity. Circulating proteomic and microRNA signatures, fibulin-3, tumor cell gene-ratio test, transcriptomic, lncRNA, glycopeptides, pleural fluid FISH assay, hyaluronate/N-ERC mesothelin and deformability cytometry may be important future markers. Putative predictive markers for pemetrexed-platinum are tumor TS and TYMS, for vinorelbine the ERCC1, beta-tubuline class III and BRCA1. Mutations of the BAP1 gene are potential markers of MPM susceptibility. In conclusion, the current status of MPM biomarkers is not satisfactory but encouraging as more sensitive and specific non-invasive markers are emerging. However, prospective validation is needed before clinical application.}, } @article {pmid25975982, year = {2015}, author = {Chew, SH and Toyokuni, S}, title = {Malignant mesothelioma as an oxidative stress-induced cancer: An update.}, journal = {Free radical biology & medicine}, volume = {86}, number = {}, pages = {166-178}, doi = {10.1016/j.freeradbiomed.2015.05.002}, pmid = {25975982}, issn = {1873-4596}, mesh = {Animals ; Asbestos/toxicity ; Biomarkers, Tumor/metabolism ; DNA Damage ; Environmental Exposure ; Humans ; Lung Neoplasms/diagnosis/etiology/*metabolism ; Mesothelioma/diagnosis/etiology/*metabolism ; Mesothelioma, Malignant ; *Oxidative Stress ; Signal Transduction ; }, abstract = {Malignant mesothelioma (MM) is a relatively rare cancer that occurs almost exclusively following respiratory exposure to asbestos in humans. Its pathogenesis is closely associated with iron overload and oxidative stress in mesothelial cells. On fiber exposure, mesothelial cells accumulate fibers simultaneously with iron, which either performs physical scissor function or catalyzes free radical generation, leading to oxidative DNA damage such as strand breaks and base modifications, followed by activation of intracellular signaling pathways. Chrysotile, per se without iron, causes massive hemolysis and further adsorbs hemoglobin. Exposure to indigestible foreign materials also induces chronic inflammation, involving consistent generation of free radicals and subsequent activation of NALP3 inflammasomes in macrophages. All of these contribute to mesothelial carcinogenesis. Genomic alterations most frequently involve homozygous deletion of INK4A/4B, and other pathways such as Hippo and TGF-β pathways are also affected in MM. Recently, analyses of familial MM sorted out BAP1 as a novel responsible tumor suppressor gene, whose function is not fully elucidated. Five-year survival of mesothelioma is still ~8%, and this cancer is increasing worldwide. Connective tissue growth factor, a secretory protein creating a vicious cycle mediated by β-catenin, has been recognized as a hopeful target for therapy, especially in sarcomatoid subtype. Recent research outcomes related to microRNAs and cancer stem cells also offer additional novel targets for the treatment of MM. Iron reduction as chemoprevention of mesothelioma is helpful at least in an animal preclinical study. Integrated approaches to fiber-induced oxidative stress would be necessary to overcome this currently fatal disease.}, } @article {pmid25950487, year = {2015}, author = {Echeverry, N and Ziltener, G and Barbone, D and Weder, W and Stahel, RA and Broaddus, VC and Felley-Bosco, E}, title = {Inhibition of autophagy sensitizes malignant pleural mesothelioma cells to dual PI3K/mTOR inhibitors.}, journal = {Cell death & disease}, volume = {6}, number = {5}, pages = {e1757}, pmid = {25950487}, issn = {2041-4889}, mesh = {Autophagy/drug effects ; Bridged Bicyclo Compounds, Heterocyclic/*pharmacology ; Cell Proliferation/drug effects ; Drug Synergism ; Humans ; Imidazoles/*pharmacology ; Lung Neoplasms/*drug therapy/*metabolism/pathology ; Mesothelioma/*drug therapy/*metabolism/pathology ; Mesothelioma, Malignant ; Phosphatidylinositol 3-Kinases/metabolism ; *Phosphoinositide-3 Kinase Inhibitors ; Phosphorylation ; Pleural Neoplasms/*drug therapy/metabolism/pathology ; Protein Kinase Inhibitors/pharmacology ; Pyrimidines/*pharmacology ; Quinolines/*pharmacology ; Signal Transduction ; TOR Serine-Threonine Kinases/*antagonists & inhibitors/metabolism ; }, abstract = {Malignant pleural mesothelioma (MPM) originates in most of the cases from chronic inflammation of the mesothelium due to exposure to asbestos fibers. Given the limited effect of chemotherapy, a big effort is being made to find new treatment options. The PI3K/mTOR pathway was reported to be upregulated in MPM. We tested the cell growth inhibition properties of two dual PI3K/mTOR inhibitors NVP-BEZ235 and GDC-0980 on 19 MPM cell lines. We could identify resistant and sensitive lines; however, there was no correlation to the downregulation of PI3K/mTOR activity markers. As a result of mTOR inhibition, both drugs efficiently induced long-term autophagy but not cell death. Autophagy blockade by chloroquine in combination with the dual PI3K/mTOR inhibitors significantly induced caspase-independent cell death involving RIP1 in the sensitive cell line SPC212. Cell death in the resistant cell line Mero-82 was less pronounced, and it was not induced via RIP1-dependent mechanism, suggesting the involvement of RIP1 downstream effectors. Cell death induction was confirmed in 3D systems. Based on these results, we identify autophagy as one of the main mechanisms of cell death resistance against dual PI3K/mTOR inhibitors in MPM. As PI3K/mTOR inhibitors are under investigation in clinical trials, these results may help interpreting their outcome and suggest ways for intervention.}, } @article {pmid25941579, year = {2014}, author = {Ranki, T and Joensuu, T and Jäger, E and Karbach, J and Wahle, C and Kairemo, K and Alanko, T and Partanen, K and Turkki, R and Linder, N and Lundin, J and Ristimäki, A and Kankainen, M and Hemminki, A and Backman, C and Dienel, K and von Euler, M and Haavisto, E and Hakonen, T and Juhila, J and Jaderberg, M and Priha, P and Vassilev, L and Vuolanto, A and Pesonen, S}, title = {Local treatment of a pleural mesothelioma tumor with ONCOS-102 induces a systemic antitumor CD8[+] T-cell response, prominent infiltration of CD8[+] lymphocytes and Th1 type polarization.}, journal = {Oncoimmunology}, volume = {3}, number = {10}, pages = {e958937}, pmid = {25941579}, issn = {2162-4011}, abstract = {Late stage cancer is often associated with reduced immune recognition and a highly immunosuppressive tumor microenvironment. The presence of tumor infiltrating lymphocytes (TILs) and specific gene-signatures prior to treatment are linked to good prognosis, while the opposite is true for extensive immunosuppression. The use of adenoviruses as cancer vaccines is a form of active immunotherapy to initialise a tumor-specific immune response that targets the patient's unique tumor antigen repertoire. We report a case of a 68-year-old male with asbestos-related malignant pleural mesothelioma who was treated in a Phase I study with a granulocyte-macrophage colony‑stimulating factor (GM-CSF)-expressing oncolytic adenovirus, Ad5/3-D24-GMCSF (ONCOS-102). The treatment resulted in prominent infiltration of CD8[+] lymphocytes to tumor, marked induction of systemic antitumor CD8[+] T-cells and induction of Th1-type polarization in the tumor. These results indicate that ONCOS-102 treatment sensitizes tumors to other immunotherapies by inducing a T-cell positive phenotype to an initially T-cell negative tumor.}, } @article {pmid25941264, year = {2015}, author = {Dummer, T and Gotay, C}, title = {Asbestos in Canada: time to change our legacy.}, journal = {CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne}, volume = {187}, number = {10}, pages = {E315-E316}, pmid = {25941264}, issn = {1488-2329}, mesh = {Asbestos/adverse effects ; Asbestos, Serpentine/*adverse effects ; Canada ; *Health Policy ; Humans ; Industry/*legislation & jurisprudence ; *International Cooperation ; Lung Neoplasms/*chemically induced ; Mesothelioma/*chemically induced ; }, } @article {pmid25940505, year = {2015}, author = {Xu, J and Alexander, DB and Iigo, M and Hamano, H and Takahashi, S and Yokoyama, T and Kato, M and Usami, I and Tokuyama, T and Tsutsumi, M and Tamura, M and Oguri, T and Niimi, A and Hayashi, Y and Yokoyama, Y and Tonegawa, K and Fukamachi, K and Futakuchi, M and Sakai, Y and Suzui, M and Kamijima, M and Hisanaga, N and Omori, T and Nakae, D and Hirose, A and Kanno, J and Tsuda, H}, title = {Chemokine (C-C motif) ligand 3 detection in the serum of persons exposed to asbestos: A patient-based study.}, journal = {Cancer science}, volume = {106}, number = {7}, pages = {825-832}, pmid = {25940505}, issn = {1349-7006}, mesh = {Adult ; Aged ; Asbestos/*toxicity ; Biomarkers, Tumor/*blood ; Carcinogens/*toxicity ; Case-Control Studies ; Chemokine CCL3/*blood ; *Environmental Exposure ; Female ; Humans ; Lung Neoplasms/*blood/chemically induced ; Male ; Mesothelioma/*blood/chemically induced ; Mesothelioma, Malignant ; Middle Aged ; }, abstract = {Exposure to asbestos results in serious risk of developing lung and mesothelial diseases. Currently, there are no biomarkers that can be used to diagnose asbestos exposure. The purpose of the present study was to determine whether the levels or detection rate of chemokine (C-C motif) ligand 3 (CCL3) in the serum are elevated in persons exposed to asbestos. The primary study group consisted of 76 healthy subjects not exposed to asbestos and 172 healthy subjects possibly exposed to asbestos. The secondary study group consisted of 535 subjects possibly exposed to asbestos and diagnosed with pleural plaque (412), benign hydrothorax (10), asbestosis (86), lung cancer (17), and malignant mesothelioma (10). All study subjects who were possibly exposed to asbestos had a certificate of asbestos exposure issued by the Japanese Ministry of Health, Labour and Welfare. For the primary study group, levels of serum CCL3 did not differ between the two groups. However, the detection rate of CCL3 in the serum of healthy subjects possibly exposed to asbestos (30.2%) was significantly higher (P < 0.001) than for the control group (6.6%). The pleural plaque, benign hydrothorax, asbestosis, and lung cancer groups had serum CCL3 levels and detection rates similar to that of healthy subjects possibly exposed to asbestos. The CCL3 chemokine was detected in the serum of 9 of the 10 patients diagnosed with malignant mesothelioma. Three of the patients with malignant mesothelioma had exceptionally high CCL3 levels. Malignant mesothelioma cells from four biopsy cases and an autopsy case were positive for CCL3, possibly identifying the source of the CCL3 in the three malignant mesothelioma patients with exceptionally high serum CCL3 levels. In conclusion, a significantly higher percentage of healthy persons possibly exposed to asbestos had detectable levels of serum CCL3 compared to healthy unexposed control subjects.}, } @article {pmid25927434, year = {2015}, author = {Creaney, J and Dick, IM and Robinson, BW}, title = {Discovery of new biomarkers for malignant mesothelioma.}, journal = {Current pulmonology reports}, volume = {4}, number = {1}, pages = {15-21}, pmid = {25927434}, issn = {2199-2428}, abstract = {Malignant mesothelioma is an asbestos-induced, aggressive tumour with limited treatment options and very poor outcome. Currently, there are no tumour biomarkers in widespread clinical use for this disease. Soluble mesothelin is the most intensively investigated mesothelioma biomarker and has been approved by the US FDA primarily as a tool for monitoring patient response and progression. Mesothelin is elevated in the blood and effusions of patients with mesothelioma, and is rarely elevated in people with benign disease with normal renal function. However, the sensitivity of mesothelin limits its use as a stand-alone tool for the screening of the asymptomatic asbestos-exposed population-one of the primary aims of mesothelioma biomarker studies. Thus, there is an intense research effort focused on the identification of new and/or novel biomarkers for mesothelioma. Some of the challenges associated with biomarker discovery in mesothelioma are discussed.}, } @article {pmid25915724, year = {2015}, author = {Yamashita, K and Nagai, H and Toyokuni, S}, title = {Receptor role of the annexin A2 in the mesothelial endocytosis of crocidolite fibers.}, journal = {Laboratory investigation; a journal of technical methods and pathology}, volume = {95}, number = {7}, pages = {749-764}, pmid = {25915724}, issn = {1530-0307}, mesh = {Adsorption ; Animals ; Annexin A2/antagonists & inhibitors/genetics/*metabolism ; Antigens, CD/genetics ; Asbestos, Crocidolite/*toxicity ; Asbestos, Serpentine/*toxicity ; Blotting, Western ; Cell Line, Tumor ; *Endocytosis ; Epithelium/metabolism ; Gene Knockdown Techniques ; Humans ; Lung Neoplasms/*chemically induced ; Mass Spectrometry ; Membrane Proteins/chemistry ; Mesothelioma/*chemically induced ; Mesothelioma, Malignant ; Rats ; Receptors, Transferrin/genetics ; }, abstract = {Asbestos-induced mesothelioma is a worldwide problem. Parietal mesothelial cells internalize asbestos fibers that traverse the entire lung parenchyma, an action that is linked to mesothelial carcinogenesis. Thus far, vitronectin purified from serum reportedly enhances the internalization of crocidolite by mesothelial cells via integrin αvβ5. To reveal another mechanism by which mesothelial cells endocytose (phagocytose) asbestos, we first evaluated the effects of serum on asbestos uptake, which proved to be nonessential. Thereafter, we undertook a study to identify proteins on the surface of mesothelial cells (MeT5A) that act as receptors for asbestos uptake based on the assumption that receptors bind to asbestos with physical affinity. To this end, we incubated the membrane fraction of MeT5A cells with crocidolite or chrysotile and evaluated the adsorbed proteins using sodium dodecyl sulfate polyacrylamide gel analysis. Next, we extensively identified the proteins using an in-solution or in-gel digestion coupled with mass spectrometry. Among the identified proteins, annexin A2 (ANXA2) and transferrin receptor protein 1 (TFRC) were distinguished because of their high score and presence at the cell surface. Crocidolite uptake by MeT5A cells was significantly decreased by shRNA (short hairpin RNA)-induced knockdown of ANXA2 and direct blockade of cell surface ANXA2 using anti-ANXA2 antibody. In addition, abundant ANXA2 protein was present on the cell membrane of mesothelial cells, particularly facing the somatic cavity. These findings demonstrate that ANXA2 has a role in the mesothelial phagocytosis of crocidolite and may serve as its receptor.}, } @article {pmid25902174, year = {2015}, author = {Miyanaga, A and Masuda, M and Tsuta, K and Kawasaki, K and Nakamura, Y and Sakuma, T and Asamura, H and Gemma, A and Yamada, T}, title = {Hippo pathway gene mutations in malignant mesothelioma: revealed by RNA and targeted exon sequencing.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {10}, number = {5}, pages = {844-851}, doi = {10.1097/JTO.0000000000000493}, pmid = {25902174}, issn = {1556-1380}, mesh = {Acyltransferases ; Adaptor Proteins, Signal Transducing/genetics/metabolism ; Apoptosis Regulatory Proteins ; Cadherins/genetics ; Cell Cycle Proteins/metabolism ; Cell Line, Tumor ; Exome ; Humans ; Intracellular Signaling Peptides and Proteins/metabolism ; Mesothelioma/*genetics/metabolism ; Monomeric GTP-Binding Proteins/genetics ; Mutation ; Neurofibromin 2/genetics/metabolism ; Oncogene Proteins, Fusion/*genetics ; Phosphoproteins/genetics/metabolism ; Presenilin-1/*genetics ; Protein Serine-Threonine Kinases/*genetics/metabolism ; Recombinant Fusion Proteins/genetics ; Sequence Analysis, DNA ; Sequence Analysis, RNA ; Signal Transduction/*genetics ; Transcription Factors/metabolism ; Transcriptome ; Tumor Suppressor Proteins/genetics/metabolism ; YAP-Signaling Proteins ; }, abstract = {INTRODUCTION: Malignant mesothelioma (MM) is an aggressive neoplasm causatively associated with exposure to asbestos. MM is rarely responsive to conventional cytotoxic drugs, and the outcome remains dismal. It is, therefore, necessary to identify the signaling pathways that drive MM and to develop new therapeutics specifically targeting the molecules involved.

METHODS: We performed comprehensive RNA sequencing of 12 MM cell lines and four clinical samples using so-called next-generation sequencers.

RESULTS: We found 15 novel fusion transcripts including one derived from chromosomal translocation between the large tumor suppressor 1 (LATS1) and presenilin-1 (PSEN1) genes. LATS1 is one of the central players of the emerging Hippo signaling pathway. The LATS1-PSEN1 fusion gene product lacked the ability to phosphorylate yes-associated protein and to suppress the growth of a MM cell line. The wild-type LATS1 allele was undetectable in this cell line, indicating two-hit genetic inactivation of its tumor suppressor function. Using pathway-targeted exon sequencing, we further identified a total of 11 somatic mutations in four Hippo pathway genes (neurofibromatosis type 2 [NF2], LATS2, RASSF1, and SAV1) in 35% (8 of 23) of clinical samples. Nuclear staining of yes-associated protein was detected in 55% (24 of 44) of the clinical samples. Expression and/or phosphorylation of the Hippo signaling proteins, RASSF1, Merlin (NF2), LATS1, and LATS2, was frequently absent.

CONCLUSIONS: The frequent alterations of Hippo pathway molecules found in this study indicate the therapeutic feasibility of targeting this pathway in patients with MM.}, } @article {pmid25896339, year = {2015}, author = {Lee, YJ and Lee, DM and Lee, SH}, title = {Nrf2 Expression and Apoptosis in Quercetin-treated Malignant Mesothelioma Cells.}, journal = {Molecules and cells}, volume = {38}, number = {5}, pages = {416-425}, pmid = {25896339}, issn = {0219-1032}, mesh = {Antioxidants/*pharmacology ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Drug Resistance, Neoplasm/drug effects ; Drug Synergism ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Mesothelioma/drug therapy/genetics/*metabolism ; NF-E2-Related Factor 2/antagonists & inhibitors/genetics/*metabolism ; Quercetin/*pharmacology ; RNA, Small Interfering/*pharmacology ; Up-Regulation/drug effects ; }, abstract = {NF-E2-related factor 2 (Nrf2), a basic leucine zipper transcription factor, has recently received a great deal of attention as an important molecule that enhances antioxidative defenses and induces resistance to chemotherapy or radiotherapy. In this study, we investigated the apoptosis-inducing and Nrf2-upregulating effects of quercetin on malignant mesothelioma (MM) MSTO-211H and H2452 cells. Quercetin treatment inhibited cell growth and led to upregulation of Nrf2 at both the mRNA and protein levels without altering the ubiquitination and extending the half-life of the Nrf2 protein. Following treatment with quercetin, analyses of the nuclear level of Nrf2, Nrf2 antioxidant response element-binding assay, Nrf2 promoter-luc assay, and RT-PCR toward the Nrf2-regulated gene, heme oxygenase-1, demonstrated that the induced Nrf2 is transcriptionally active. Knockdown of Nrf2 expression with siRNA enhanced cytotoxicity due to the induction of apoptosis, as evidenced by an increase in the level of proapoptotic Bax, a decrease in the level of antiapoptotic Bcl-2 with enhanced cleavage of caspase-3 and PARP proteins, the appearance of a sub-G0/G1 peak in the flow cytometric assay, and increased percentage of apoptotic propensities in the annexin V binding assay. Effective reversal of apoptosis was observed following pretreatment with the pan-caspase inhibitor Z-VAD. Moreover, Nrf2 knockdown exhibited increased sensitivity to the anticancer drug, cisplatin, presumably by potentiating the oxidative stress induced by cisplatin. Collectively, our data demonstrate the importance of Nrf2 in cytoprotection, survival, and drug resistance with implications for the potential significance of targeting Nrf2 as a promising strategy for overcoming resistance to chemotherapeutics in MM.}, } @article {pmid25889843, year = {2015}, author = {Alakus, H and Yost, SE and Woo, B and French, R and Lin, GY and Jepsen, K and Frazer, KA and Lowy, AM and Harismendy, O}, title = {BAP1 mutation is a frequent somatic event in peritoneal malignant mesothelioma.}, journal = {Journal of translational medicine}, volume = {13}, number = {}, pages = {122}, pmid = {25889843}, issn = {1479-5876}, support = {U54 HL108460/HL/NHLBI NIH HHS/United States ; U54HL108460/HL/NHLBI NIH HHS/United States ; R21 CA177519/CA/NCI NIH HHS/United States ; P30 CA023100/CA/NCI NIH HHS/United States ; P30CA023100/CA/NCI NIH HHS/United States ; TL1 TR000098/TR/NCATS NIH HHS/United States ; R21CA177519/CA/NCI NIH HHS/United States ; }, mesh = {DNA Copy Number Variations/genetics ; *Genetic Predisposition to Disease ; Humans ; Lung Neoplasms/*genetics ; Mesothelioma/*genetics ; Mesothelioma, Malignant ; Mutation/*genetics ; Peritoneal Neoplasms/*genetics ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {BACKGROUND: Malignant mesothelioma (MM) arises from mesothelial cells that line the pleural, peritoneal and pericardial surfaces. The majority of MMs are pleural and have been associated with asbestos exposure. Previously, pleural MMs have been genetically characterized by the loss of BAP1 (40-60%) as well as loss of NF2 (75%) and CDKN2A (60%). The rare peritoneal form of MM occurs in ~10% cases. With only ~300 cases diagnosed in the US per year, its link to asbestos exposure is not clear and its mutational landscape unknown.

METHODS: We analyzed the somatic mutational landscape of 12 peritoneal MM of epitheloid subtype using copy number analysis (N = 9), whole exome sequencing (N = 7) and targeted sequencing (N = 12).

RESULTS: Peritoneal MM display few copy number alterations, with most samples having less than 10 Mbp total changes, mostly through deletions and no high copy number amplification. Chromosome band 3p21 encoding BAP1 is the most recurrently deleted region (5/9), while, in contrast to pleural MM, NF2 and CDKN2A are not affected. We further identified 87 non-silent mutations across 7 sequenced tumors, with a median of 8 mutated genes per tumor, resulting in a very low mutation rate (median 1.3 10(-6)). BAP1 was the only recurrently mutated gene (N = 3/7). In one additional case, loss of the entire chromosome 3 leaves a non-functional copy of BAP1 carrying a rare nonsense germline variant, thus suggesting a potential genetic predisposition in this patient. Finally, with targeted sequencing of BAP1 in 3 additional cases, we conclude that BAP1 is frequently altered through copy number losses (N = 3/12), mutations (N = 3/12) or both (N = 2/12) sometimes at a sub-clonal level.

CONCLUSION: Our findings suggest a major role for BAP1 in peritoneal MM susceptibility and oncogenesis and indicate important molecular differences to pleural MM as well as potential strategies for therapy and prevention.}, } @article {pmid25885893, year = {2015}, author = {Corfiati, M and Scarselli, A and Binazzi, A and Di Marzio, D and Verardo, M and Mirabelli, D and Gennaro, V and Mensi, C and Schallemberg, G and Merler, E and Negro, C and Romanelli, A and Chellini, E and Silvestri, S and Cocchioni, M and Pascucci, C and Stracci, F and Romeo, E and Trafficante, L and Angelillo, I and Menegozzo, S and Musti, M and Cavone, D and Cauzillo, G and Tallarigo, F and Tumino, R and Melis, M and Iavicoli, S and Marinaccio, A and , }, title = {Epidemiological patterns of asbestos exposure and spatial clusters of incident cases of malignant mesothelioma from the Italian national registry.}, journal = {BMC cancer}, volume = {15}, number = {}, pages = {286}, pmid = {25885893}, issn = {1471-2407}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Bayes Theorem ; Child ; Child, Preschool ; Cluster Analysis ; Environmental Exposure/*adverse effects ; Female ; Geography ; Humans ; Incidence ; Infant ; Infant, Newborn ; Italy/epidemiology ; Lung Neoplasms/*epidemiology/*etiology ; Male ; Mesothelioma/*epidemiology/*etiology ; Mesothelioma, Malignant ; Middle Aged ; Registries ; Spatial Analysis ; Young Adult ; }, abstract = {BACKGROUND: Previous ecological spatial studies of malignant mesothelioma cases, mostly based on mortality data, lack reliable data on individual exposure to asbestos, thus failing to assess the contribution of different occupational and environmental sources in the determination of risk excess in specific areas. This study aims to identify territorial clusters of malignant mesothelioma through a Bayesian spatial analysis and to characterize them by the integrated use of asbestos exposure information retrieved from the Italian national mesothelioma registry (ReNaM).

METHODS: In the period 1993 to 2008, 15,322 incident cases of all-site malignant mesothelioma were recorded and 11,852 occupational, residential and familial histories were obtained by individual interviews. Observed cases were assigned to the municipality of residence at the time of diagnosis and compared to those expected based on the age-specific rates of the respective geographical area. A spatial cluster analysis was performed for each area applying a Bayesian hierarchical model. Information about modalities and economic sectors of asbestos exposure was analyzed for each cluster.

RESULTS: Thirty-two clusters of malignant mesothelioma were identified and characterized using the exposure data. Asbestos cement manufacturing industries and shipbuilding and repair facilities represented the main sources of asbestos exposure, but a major contribution to asbestos exposure was also provided by sectors with no direct use of asbestos, such as non-asbestos textile industries, metal engineering and construction. A high proportion of cases with environmental exposure was found in clusters where asbestos cement plants were located or a natural source of asbestos (or asbestos-like) fibers was identifiable. Differences in type and sources of exposure can also explain the varying percentage of cases occurring in women among clusters.

CONCLUSIONS: Our study demonstrates shared exposure patterns in territorial clusters of malignant mesothelioma due to single or multiple industrial sources, with major implications for public health policies, health surveillance, compensation procedures and site remediation programs.}, } @article {pmid25877069, year = {2015}, author = {Blum, W and Pecze, L and Felley-Bosco, E and Worthmüller-Rodriguez, J and Wu, L and Vrugt, B and de Perrot, M and Schwaller, B}, title = {Establishment of immortalized murine mesothelial cells and a novel mesothelioma cell line.}, journal = {In vitro cellular & developmental biology. Animal}, volume = {51}, number = {7}, pages = {714-721}, pmid = {25877069}, issn = {1543-706X}, mesh = {Animals ; Antigens, Polyomavirus Transforming/metabolism ; Cell Line, Transformed ; *Cell Line, Tumor ; Cell Proliferation ; Epithelial Cells/pathology ; GPI-Linked Proteins/metabolism ; Lung Neoplasms/*pathology ; Mesothelin ; Mesothelioma/*pathology ; Mesothelioma, Malignant ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Neurofibromin 2/genetics ; Xenograft Model Antitumor Assays ; }, abstract = {Mesothelial cells are susceptible to asbestos fiber-induced cytotoxicity and on longer time scales to transformation; the resulting mesothelioma is a highly aggressive neoplasm that is considered as incurable at the present time Zucali et al. (Cancer Treatment Reviews 37:543-558, 2011). Only few murine cell culture models of immortalized mesothelial cells and mesothelioma cell lines exist to date. We generated SV40-immortalized cell lines derived from wild-type (WT) and neurofibromatosis 2 (merlin) heterozygote (Nf2+/-) mice, both on a commonly used genetic background, C57Bl/6J. All immortalized mesothelial clones consistently grow in DMEM supplemented with fetal bovine serum. Cells can be passaged for more than 40 times without any signs of morphological changes or a decrease in proliferation rate. The tumor suppressor gene NF2 is one of the most frequently mutated genes in human mesothelioma, but its detailed function is still unknown. Thus, these genotypically distinct cell lines likely relevant for malignant mesothelioma formation are expected to serve as useful in vitro models, in particular to compare with in vivo studies in mice of the same genotype. Furthermore, we generated a novel murine mesothelioma cell line RN5 originating from an Nf2+/- mouse subjected to repeated crocidolite exposure. RN5 cells are highly tumorigenic.}, } @article {pmid25876702, year = {2015}, author = {Lee, R and Van Orden, D}, title = {RE: Gordon R, Fitzgerald S, and Millette J. Asbestos in commercial cosmetic talcum powder as a cause of mesothelioma in women. Int J Occup Environ Health. 2014;20(4):318-332.}, journal = {International journal of occupational and environmental health}, volume = {}, number = {}, pages = {2049396715Y0000000005}, doi = {10.1179/2049396715Y.0000000005}, pmid = {25876702}, issn = {2049-3967}, } @article {pmid25874240, year = {2015}, author = {Szeszenia-Dąbrowska, N and Świątkowska, B}, title = {An unjustified prognosis of the number of asbestos-related lung cancer cases caused by an increase in airborne asbestos concentrations as a result of removing of asbestos-cement products.}, journal = {TheScientificWorldJournal}, volume = {2015}, number = {}, pages = {264568}, pmid = {25874240}, issn = {1537-744X}, mesh = {Asbestos/*adverse effects ; Humans ; Lung Neoplasms/*epidemiology ; Mesothelioma/*epidemiology ; Occupational Diseases/*epidemiology ; *Occupational Exposure ; }, } @article {pmid25856259, year = {2015}, author = {Wolff-Bar, M and Dujovny, T and Vlodavsky, E and Postovsky, S and Morgenstern, S and Braslavsky, D and Nissan, A and Steinberg, R and Feinmesser, M}, title = {An 8-Year-Old Child with Malignant Deciduoid Mesothelioma of the Abdomen: Report of a Case and Review of the Literature.}, journal = {Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society}, volume = {18}, number = {4}, pages = {327-330}, doi = {10.2350/14-06-1511-CR.1}, pmid = {25856259}, issn = {1093-5266}, mesh = {Abdominal Pain/etiology ; Biopsy ; Child ; Female ; Humans ; Mesothelioma/complications/*pathology/therapy ; Peritoneal Neoplasms/complications/*pathology/therapy ; Treatment Outcome ; }, abstract = {Malignant mesothelioma is an uncommon tumor that usually arises in the pleural cavity of adults with a history of asbestos exposure. Less frequently, it appears in the peritoneum or other mesothelial surfaces. Deciduoid mesothelioma is a rare subtype that has been found at both sites. Of the 3 reported cases in children, 2 originated in the mesenterium and 1 in the pleura. We describe a 4th case of pediatric, malignant, deciduoid mesothelioma and a third case in the mesenteric cavity. The patient was an 8-year-old girl who presented with abdominal pain and fullness. Workup revealed extensive involvement of the abdomen by a serosa-based tumor. The clinical and pathologic findings are described, and the pertinent literature is reviewed.}, } @article {pmid25847205, year = {2015}, author = {Challita, S and Guerder, A and Charpentier, MC and Daher, M and Giraud, F and Roche, N}, title = {[Mesothelioma and familial Mediterranean fever: A relationship?].}, journal = {Revue des maladies respiratoires}, volume = {32}, number = {3}, pages = {271-274}, doi = {10.1016/j.rmr.2014.06.029}, pmid = {25847205}, issn = {1776-2588}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Causality ; Colchicine/therapeutic use ; Familial Mediterranean Fever/*complications/drug therapy/pathology ; Female ; Humans ; Inflammation ; Lebanon/ethnology ; Mesothelioma/diagnosis/drug therapy/*etiology ; Middle Aged ; Organoplatinum Compounds/administration & dosage ; Pemetrexed/administration & dosage ; Peritoneum/pathology ; Pleural Neoplasms/diagnosis/drug therapy/*etiology ; Serous Membrane/pathology ; }, abstract = {INTRODUCTION: The majority of pleural and peritoneal mesotheliomas are linked to asbestos exposure but, in around 20% of cases, no history of such exposure is found. Periodic disease is associated with recurrent serositis, which could favor the development of mesothelioma.

CASE REPORT: We report a case of pleural mesothelioma in a 50-year-old Lebanese woman, with no detectable exposure to asbestos but suffering from periodic disease (familial Mediterranean fever) with recurrent episodes of serositis.

DISCUSSION: Many cases of peritoneal mesothelioma in patients with FMF are reported in the literature. This is the second reported case of pleural mesothelioma associated with periodic disease. Because of the low incidence of both diseases, further publications are required to support the hypothesis of a causal link. It is important, therefore, that all cases of an association of periodic disease and mesothelioma are reported.}, } @article {pmid25844559, year = {2015}, author = {Li, X and Brownlee, NA and Sporn, TA and Mahar, A and Roggli, VL}, title = {Malignant (Diffuse) Mesothelioma in Patients With Hematologic Malignancies: A Clinicopathologic Study of 45 Cases.}, journal = {Archives of pathology & laboratory medicine}, volume = {139}, number = {9}, pages = {1129-1136}, doi = {10.5858/arpa.2014-0569-OA}, pmid = {25844559}, issn = {1543-2165}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Child ; Female ; Hematologic Neoplasms/*pathology/radiotherapy ; Hodgkin Disease/pathology ; Humans ; Kaplan-Meier Estimate ; Leukemia, Lymphocytic, Chronic, B-Cell/pathology ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology ; Lung Neoplasms/etiology/mortality/*pathology ; Lymphoma, Non-Hodgkin/pathology ; Male ; Mesothelioma/etiology/mortality/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Neoplasms, Multiple Primary/etiology/*pathology ; Neoplasms, Radiation-Induced/etiology/pathology ; Radiotherapy/adverse effects ; Risk Factors ; Time Factors ; Young Adult ; }, abstract = {CONTEXT: Ionizing radiation has a role in the development of malignant mesothelioma, in several epidemiologic studies, including patients with hematologic malignancies.

OBJECTIVE: To study the clinicopathologic characteristics of patients with malignant mesothelioma and hematologic malignancies with and without a history of radiotherapy.

DESIGN: From a database of approximately 3600 patients with malignant mesothelioma, we identified 45 patients (1%) who also had hematologic malignancies. We examined clinicopathologic features and noted whether the patient had received radiotherapy for malignancy, comparing those with and those without such exposure.

RESULTS: Among the 45 cases, 18 (40%) had Hodgkin lymphoma, 15 (33%) had non-Hodgkin lymphoma, 10 (4%) had chronic lymphocytic leukemia, and 2 (22%) had chronic myelogenous leukemia; 20 patients (44%) had a history of radiotherapy, and 23 (51%) did not. Most patients with Hodgkin lymphoma (16 of 18; 90.0%) received radiation, whereas none of the patients with leukemia (0 of 12) and only 20% (3 of 15) of the patients with non-Hodgkin lymphoma did so. Patients without radiation were older than patients who received radiotherapy (median, 73 versus 54 years, respectively; P < .001), had a shorter interval from diagnosis of hematologic malignancy to that of mesothelioma (median, 2 versus 24 years, respectively; P < .001), and had a shorter survival period (median, 6.0 versus 14.0 months, respectively; P = .02). Epithelial mesotheliomas were proportionately more common in patients with a history of radiotherapy.

CONCLUSIONS: Patients with mesothelioma and hematologic malignancies with a history of radiation tended to be younger, had a longer interval from diagnosis of hematologic malignancy to that of mesothelioma, had a longer survival period, and were more likely to have the epithelial variant compared with patients without radiotherapy.}, } @article {pmid25842376, year = {2015}, author = {Finkelstein, MM}, title = {Asbestos fibres in the lungs of an American mechanic who drilled, riveted, and ground brake linings: a case report and discussion.}, journal = {The Annals of occupational hygiene}, volume = {59}, number = {4}, pages = {525-527}, doi = {10.1093/annhyg/mev008}, pmid = {25842376}, issn = {1475-3162}, mesh = {Air Pollutants, Occupational/*adverse effects ; Asbestos/adverse effects/*analysis ; Automobiles ; Fatal Outcome ; Humans ; Inhalation Exposure/*analysis ; Lung/*chemistry/ultrastructure ; Lung Neoplasms/*chemically induced ; Male ; Mesothelioma/*chemically induced ; Occupational Exposure/analysis ; }, abstract = {In North America and Europe, the use of asbestos in friction products was discontinued before the end of the 20th century. In the developing world, the use of asbestos-containing friction products continues. In 2010, Cely-Garcia and colleagues (Cely-Garcia et al., 2012) sampled three brake repair shops located in Bogota, Colombia. Both asbestos and non-asbestos containing brake linings were sold separately or attached to a shoe. When brake linings are sold separated from the shoe, they must be manipulated to attach them to the shoe before installation. The process starts with the removal of the old brake shoe from the vehicle's brake drum. If the existing brake shoe is to be reused, the old lining needs to be removed and the old shoe must be ground to prepare it for a new lining. Riveting requires drilling holes in the linings and shoes and before installing rivets, the lining must be countersunk. The borders of the lining are bevelled. On some occasions, the entire exposed surface of the lining is ground to make it thinner. Once attached to the shoe, the edges of brake linings may extend beyond the shoe. In this case, it is necessary to cut or grind the edges to match the lining to the shoe before bevelling or grinding. The authors reported that 'the sampling results indicate that the brake mechanics sampled are exposed to extremely high asbestos concentrations (i.e. based on transmission electron microscopy counts), suggesting that this occupational group could be at excess risk of asbestos-related diseases'.}, } @article {pmid25841001, year = {2015}, author = {van Oyen, SC and Peters, S and Alfonso, H and Fritschi, L and de Klerk, NH and Reid, A and Franklin, P and Gordon, L and Benke, G and Musk, AW}, title = {Development of a Job-Exposure Matrix (AsbJEM) to Estimate Occupational Exposure to Asbestos in Australia.}, journal = {The Annals of occupational hygiene}, volume = {59}, number = {6}, pages = {737-748}, doi = {10.1093/annhyg/mev017}, pmid = {25841001}, issn = {1475-3162}, mesh = {Air Pollutants, Occupational/adverse effects/*analysis ; Asbestos/adverse effects/*analysis ; Asbestosis ; Australia ; Environmental Monitoring/*methods ; Humans ; Mesothelioma ; Occupational Diseases ; Occupational Exposure/*analysis ; *Occupations ; }, abstract = {INTRODUCTION: Occupational exposure data on asbestos are limited and poorly integrated in Australia so that estimates of disease risk and attribution of disease causation are usually calculated from data that are not specific for local conditions.

OBJECTIVE: To develop a job-exposure matrix (AsbJEM) to estimate occupational asbestos exposure levels in Australia, making optimal use of the available exposure data.

METHODS: A dossier of all available exposure data in Australia and information on industry practices and controls was provided to an expert panel consisting of three local industrial hygienists with thorough knowledge of local and international work practices. The expert panel estimated asbestos exposures for combinations of occupation, industry, and time period. Intensity and frequency grades were estimated to enable the calculation of annual exposure levels for each occupation-industry combination for each time period. Two indicators of asbestos exposure intensity (mode and peak) were used to account for different patterns of exposure between occupations. Additionally, the probable type of asbestos fibre was determined for each situation.

RESULTS: Asbestos exposures were estimated for 537 combinations of 224 occupations and 60 industries for four time periods (1943-1966; 1967-1986; 1987-2003; ≥2004). Workers in the asbestos manufacturing, shipyard, and insulation industries were estimated to have had the highest average exposures. Up until 1986, 46 occupation-industry combinations were estimated to have had exposures exceeding the current Australian exposure standard of 0.1 f ml(-1). Over 90% of exposed occupations were considered to have had exposure to a mixture of asbestos varieties including crocidolite.

CONCLUSION: The AsbJEM provides empirically based quantified estimates of asbestos exposure levels for Australian jobs since 1943. This exposure assessment application will contribute to improved understanding and prediction of asbestos-related diseases and attribution of disease causation.}, } @article {pmid25828940, year = {2015}, author = {Baas, P and Burgers, S}, title = {ASIA: asbestos stop in Asia.}, journal = {Respirology (Carlton, Vic.)}, volume = {20}, number = {4}, pages = {521}, doi = {10.1111/resp.12533}, pmid = {25828940}, issn = {1440-1843}, mesh = {*Asbestos ; *Asbestosis ; *Environmental Exposure ; Humans ; *Industry ; *Lung Neoplasms ; *Mesothelioma ; }, } @article {pmid25824152, year = {2015}, author = {Birnie, KA and Yip, YY and Ng, DC and Kirschner, MB and Reid, G and Prêle, CM and Musk, AW and Lee, YC and Thompson, PJ and Mutsaers, SE and Badrian, B}, title = {Loss of miR-223 and JNK Signaling Contribute to Elevated Stathmin in Malignant Pleural Mesothelioma.}, journal = {Molecular cancer research : MCR}, volume = {13}, number = {7}, pages = {1106-1118}, doi = {10.1158/1541-7786.MCR-14-0442}, pmid = {25824152}, issn = {1557-3125}, mesh = {Animals ; Australia ; Cell Line, Tumor ; Cell Movement ; Humans ; JNK Mitogen-Activated Protein Kinases/*metabolism ; Lung Neoplasms/*metabolism/pathology ; *MAP Kinase Signaling System ; Mesothelioma/*metabolism/pathology ; Mesothelioma, Malignant ; Mice ; MicroRNAs/*metabolism ; Paraffin Embedding ; Primary Cell Culture ; Stathmin/genetics/*metabolism ; }, abstract = {UNLABELLED: Malignant pleural mesothelioma (MPM) is often fatal, and studies have revealed that aberrant miRNAs contribute to MPM development and aggressiveness. Here, a screen of miRNAs identified reduced levels of miR-223 in MPM patient specimens. Interestingly, miR-223 targets Stathmin (STMN1), a microtubule regulator that has been associated with MPM. However, whether miR-223 regulates STMN1 in MPM and the functions of miR-223 and STMN1 in this disease are yet to be determined. STMN1 is also regulated by c-Jun N-terminal kinase (JNK) signaling, but whether this occurs in MPM and whether miR-223 plays a role are unknown. The relationship between STMN1, miR-223, and JNK was assessed using MPM cell lines, cells from pleural effusions, and MPM tissue. Evidence indicates that miR-223 is decreased in all MPM tissue compared with normal/healthy tissue. Conversely, STMN1 expression was higher in MPM cell lines when compared with primary mesothelial cell controls. Following overexpression of miR-223 in MPM cell lines, STMN1 levels were reduced, cell motility was inhibited, and tubulin acetylation induced. Knockdown of STMN1 using siRNAs led to inhibition of MPM cell proliferation and motility. Finally, miR-223 levels increased while STMN1 was reduced following the re-expression of the JNK isoforms in JNK-null murine embryonic fibroblasts, and STMN1 was reduced in MPM cell lines following the activation of JNK signaling.

IMPLICATIONS: miR-223 regulates STMN1 in MPM, and both are in turn regulated by the JNK signaling pathway. As such, miR-223 and STMN1 play an important role in regulating MPM cell motility and may be therapeutic targets.}, } @article {pmid25823924, year = {2015}, author = {Cho, JH and Lee, SJ and Oh, AY and Yoon, MH and Woo, TG and Park, BJ}, title = {NF2 blocks Snail-mediated p53 suppression in mesothelioma.}, journal = {Oncotarget}, volume = {6}, number = {12}, pages = {10073-10085}, pmid = {25823924}, issn = {1949-2553}, mesh = {Apoptosis/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Genes, Neurofibromatosis 2 ; Humans ; Lung Neoplasms/chemically induced/*etiology/genetics/pathology ; Mesothelioma/chemically induced/*etiology/genetics/pathology ; Mesothelioma, Malignant ; Naphthoquinones/pharmacology ; Neurofibromin 2/biosynthesis/genetics/*metabolism ; Phosphatidylethanolamine Binding Protein/metabolism ; Silicon Dioxide/toxicity ; Snail Family Transcription Factors ; Transcription Factors/*antagonists & inhibitors/biosynthesis/genetics ; Transfection ; Tumor Suppressor Protein p53/*antagonists & inhibitors/biosynthesis/*genetics ; }, abstract = {Although asbestos causes malignant pleural mesothelioma (MPM), rising from lung mesothelium, the molecular mechanism has not been suggested until now. Extremely low mutation rate in classical tumor suppressor genes (such as p53 and pRb) and oncogenes (including Ras or myc) indicates that there would be MPM-specific carcinogenesis pathway. To address this, we treated silica to mimic mesothelioma carcinogenesis in mesothelioma and non-small cell lung cancer cell lines (NSCLC). Treatment of silica induced p-Erk and Snail through RKIP reduction. In addition, p53 and E-cadherin were decreased by silica-treatment. Elimination of Snail restored p53 expression. We found that NF2 (frequently deleted in MPM) inhibited Snail-mediated p53 suppression and was stabilized by RKIP. Importantly, GN25, an inhibitor of p53-Snail interaction, induced p53 and apoptosis. These results indicate that MPM can be induced by reduction of RKIP/NF2, which suppresses p53 through Snail. Thus, the p53-Snail binding inhibitor such as GN25 is a drug candidate for MPM.}, } @article {pmid25821338, year = {2015}, author = {Klebe, S and Griggs, K and Cheng, Y and Driml, J and Henderson, DW and Reid, G}, title = {Blockade of aquaporin 1 inhibits proliferation, motility, and metastatic potential of mesothelioma in vitro but not in an in vivo model.}, journal = {Disease markers}, volume = {2015}, number = {}, pages = {286719}, pmid = {25821338}, issn = {1875-8630}, mesh = {Aged ; Aged, 80 and over ; Animals ; Antineoplastic Agents/*therapeutic use ; Apoptosis ; Aquaporin 1/*antagonists & inhibitors/genetics/metabolism ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Cells, Cultured ; Female ; Humans ; Male ; Mesothelioma/drug therapy/*metabolism ; Mice ; Mice, Nude ; Pleural Effusion, Malignant/drug therapy/*metabolism ; Xenograft Model Antitumor Assays ; }, abstract = {BACKGROUND: Malignant mesothelioma (MM) is an aggressive tumor of the serosal membranes, mostly the pleura. It is related to asbestos exposure and has a poor prognosis. MM has a long latency period, and incidence is predicted to remain stable or increase until 2020. Currently, no biomarkers for a specific targeted therapy are available. Previously, we observed that expression of aquaporin 1 (AQP1) was an indicator of prognosis in two independent cohorts. Here we determine whether AQP1 inhibition has therapeutic potential in the treatment of MM.

METHODS: Functional studies were performed with H226 cells and primary MM cells harvested from pleural effusions. AQP1 expression and mesothelial phenotype was determined by immunohistochemistry. AQP1 function was inhibited by a pharmacological blocker (AqB050) or AQP1-specific siRNA. Cell proliferation, migration, and anchorage-independent cell growth were assessed. A nude mouse heterotopic xenograft model of MM was utilised for the in vivo studies.

RESULTS: Inhibition of AQP1 significantly decreases cell proliferation, metastatic potential, and motility without inducing nonspecific cytotoxicity or increasing apoptosis. In vivo blockade of AQP1 had no biologically significant effect on growth of established tumours.

CONCLUSIONS: Targeted blockade of AQP1 restricts MM growth and migration in vitro. Further work is warranted to fully evaluate treatment potential in vivo.}, } @article {pmid25819225, year = {2015}, author = {Leong, SL and Zainudin, R and Kazan-Allen, L and Robinson, BW}, title = {Asbestos in Asia.}, journal = {Respirology (Carlton, Vic.)}, volume = {20}, number = {4}, pages = {548-555}, doi = {10.1111/resp.12517}, pmid = {25819225}, issn = {1440-1843}, mesh = {*Asbestos ; *Asbestosis ; Asia ; China ; *Environmental Exposure ; Humans ; Indonesia ; *Industry ; Japan ; Lung Diseases ; *Lung Neoplasms ; *Mesothelioma ; Republic of Korea ; Singapore ; }, abstract = {Asbestos is a global killer. Despite lessons learned in the developed world on the use of asbestos and its hazardous pulmonary consequences, its use continues to increase in Asia. Although some countries such as Japan, Korea and Singapore have curtailed the use of this mineral, there are numerous countries in Asia that continue to mine, import and use this fibre, particularly China, which is one of the largest consumers in the world. Numerous factors ranging from political and economic to the lack of understanding of asbestos and the management of asbestos-related lung disease are keys to this observed trend. Awareness of these factors combined with early intervention may prevent the predicted Asian 'tsunami' of asbestos diseases.}, } @article {pmid25802741, year = {2015}, author = {Mitsui, A and Saji, H and Shimmyo, T and Mochizuki, A and Kurimoto, N and Nakamura, H}, title = {Malignant pleural mesothelioma presenting as a spontaneous pneumothorax.}, journal = {Respirology case reports}, volume = {3}, number = {1}, pages = {9-12}, pmid = {25802741}, issn = {2051-3380}, abstract = {Malignant pleural mesothelioma (MPM) is thought to arise from the mesothelial cells that line the pleural cavities. Most patients initially experience the insidious onset of chest pain or shortness of breath and have a history of asbestos exposure. MPM rarely presents as spontaneous pneumothorax. We report two male patients who presented with a spontaneous hydropneumothorax. One was exposed to asbestos and the other was not. Computed tomography showed tiny nodules with pleural thickness. They both underwent pleural effusion cytology and/or pleural biopsy. Therefore, the pathological diagnosis of MPM was obtained in both cases. We also reviewed 16 Japanese MPM cases with pneumothorax including our two patients. More than half of the patients suffered from pneumothorax repeatedly. We emphasize the need to obtain a pathological diagnosis of pleural effusion cytology and/or pleural biopsy in older patients presenting with a spontaneous hydropneumothorax.}, } @article {pmid25797984, year = {2015}, author = {Toyokuni, S and Jiang, LI and Kitaura, R and Shinohara, H}, title = {Minimal inflammogenicity of pristine single-wall carbon nanotubes.}, journal = {Nagoya journal of medical science}, volume = {77}, number = {1-2}, pages = {195-202}, pmid = {25797984}, issn = {0027-7622}, abstract = {Carbon nanotubes (CNTs) are a novel synthetic material comprising only carbon atoms. Based on its rigidity, its electrical and heat conductivity and its applicability to surface manufacturing, this material is expected to have numerous applications in industry. However, due to the material's dimensional similarity to asbestos fibers, its carcinogenicity was hypothesized during the last decade, and indeed, we have shown that multi-wall CNTs (MWCNTs) of 50 nm in diameter are potently carcinogenic to mesothelial cells after intraperitoneal injection. Additionally, we suggested that inflammogenicity after intraperitoneal injection can predict mesothelial carcinogenesis. However, few data have been published on the intraperitoneal inflammogenicity of single-wall CNTs (SWCNTs). Here, we conducted a series of studies on SWCNTs using both intraperitoneal injection into rats and MeT5A mesothelial cells. Intraperitoneal injection of 10 mg SWCNTs caused no remarkable inflammation in the abdominal cavity, and the exposure of MeT5A cells to up to 25 μg/cm(2) SWCNTs did not alter proliferation. MWCNTs of 50 nm in diameter were used as a positive control, and tangled MWCNTs of 15 nm in diameter were used as a negative control. The results suggest that SWCNTs are a low-risk material with respect to mesothelial carcinogenesis.}, } @article {pmid25796603, year = {2015}, author = {Sneddon, S and Leon, JS and Dick, IM and Cadby, G and Olsen, N and Brims, F and Allcock, RJ and Moses, EK and Melton, PE and de Klerk, N and Musk, AW and Robinson, BW and Creaney, J}, title = {Absence of germline mutations in BAP1 in sporadic cases of malignant mesothelioma.}, journal = {Gene}, volume = {563}, number = {1}, pages = {103-105}, doi = {10.1016/j.gene.2015.03.031}, pmid = {25796603}, issn = {1879-0038}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Australia ; Female ; Genetic Predisposition to Disease ; *Germ-Line Mutation ; Humans ; Lung Neoplasms/chemically induced/*genetics ; Male ; Mesothelioma/chemically induced/*genetics ; Mesothelioma, Malignant ; Middle Aged ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {Malignant mesothelioma (MM) is a uniformly fatal tumour caused predominantly by exposure to asbestos. It is not known why some exposed individuals get mesothelioma and others do not. There is some epidemiological evidence of host susceptibility. BAP1 gene somatic mutations and allelic loss are common in mesothelioma and recently a BAP1 cancer syndrome was described in which affected individuals and families had an increased risk of cancer of multiple types, including MM. To determine if BAP1 mutations could underlie any of the sporadic mesothelioma cases in our cohort of patients, we performed targeted deep sequencing of the BAP1 exome on the IonTorrent Proton sequencer in 115 unrelated MM cases. No exonic germline BAP1 mutations of known functional significance were observed, further supporting the notion that sporadic germline BAP1 mutations are not relevant to the genetic susceptibility of MM.}, } @article {pmid25793652, year = {2015}, author = {Haberman, A}, title = {Unusual appearance of malignant peritoneal mesothelioma.}, journal = {Journal of computer assisted tomography}, volume = {39}, number = {3}, pages = {419-421}, doi = {10.1097/RCT.0000000000000240}, pmid = {25793652}, issn = {1532-3145}, mesh = {Adult ; Diagnosis, Differential ; Female ; Humans ; Mesothelioma/*diagnosis ; Peritoneal Neoplasms/*diagnosis ; Tomography, X-Ray Computed/*methods ; Ultrasonography/*methods ; }, abstract = {Malignant peritoneal mesothelioma (MPM) is a rare and fatal cancer arising from the mesothelial cells lining the peritoneum. This typically occurs in men in their fifth and sixth decades, but can be seen in women and any age group. Pleural and extrapleural mesothelioma can arise in the setting of asbestos exposure, but other reported causes of MPM include exposure to silicate fibers and radiation therapy. Because it presents with vague symptoms such as abdominal pain, anorexia, and weight loss, it is generally advanced at diagnosis. This is a case of MPM that presented initially at contrast-enhanced computed tomography as a small focal lesion in the lesser sac, ultimately resulting in death from complications of the disease.}, } @article {pmid25759902, year = {2014}, author = {Seldén, A and Lundgren, L and Plato, N}, title = {["Bear plug"--asbestos source in every home?].}, journal = {Lakartidningen}, volume = {111}, number = {42}, pages = {1850}, pmid = {25759902}, issn = {0023-7205}, mesh = {Asbestos, Amosite/*toxicity ; Asbestos, Crocidolite/*toxicity ; Asbestos, Serpentine/*toxicity ; Construction Industry/history ; History, 20th Century ; Humans ; Mesothelioma/etiology ; Microscopy, Electron, Scanning ; Occupational Diseases/etiology ; Occupational Exposure/adverse effects ; Pleural Neoplasms/etiology ; }, } @article {pmid25759516, year = {2015}, author = {Funahashi, S and Okazaki, Y and Ito, D and Asakawa, A and Nagai, H and Tajima, M and Toyokuni, S}, title = {Asbestos and multi-walled carbon nanotubes generate distinct oxidative responses in inflammatory cells.}, journal = {Journal of clinical biochemistry and nutrition}, volume = {56}, number = {2}, pages = {111-117}, pmid = {25759516}, issn = {0912-0009}, abstract = {Asbestos exposure is considered a social burden by causing mesothelioma. Despite the use of synthetic materials, multi-walled carbon nanotubes (MWCNTs) are similar in dimension to asbestos and produce mesothelioma in animals. The role of inflammatory cells in mesothelial carcinogenesis remains unclear. Here, we evaluated the differences in inflammatory cell responses following exposure to these fibrous materials using a luminometer and L-012 (8-amino-5-chloro-7-phenylpyrido[3,4-d]pyridazine-1,4-(2H,3H) dione) to detect reactive oxygen species (ROS). Rat peripheral blood or RAW264.7 cells were used to assess the effects on neutrophils and macrophages, respectively. Crocidolite and amosite induced significant ROS generation by neutrophils with a peak at 10 min, whereas that of chrysotile was ~25% of the crocidolite/amosite response. MWCNTs with different diameters (~15, 50, 115 and 145 nm) and different carcinogenicity did not induce significant ROS in peripheral blood. However, the MWCNTs induced a comparable amount of ROS in RAW264.7 cells to that following asbestos treatment. The peaks for MWCNTs (0.5-1.5 h) were observed earlier than those for asbestos (1-5 h). Apocynin and superoxide dismutase significantly inhibited ROS generation for each fiber, suggesting an involvement of NADPH oxidase and superoxide. Thus, asbestos and MWCNTs induce different oxidative responses in inflammatory cells, indicating the importance of mesothelial cell evaluation for carcinogenesis.}, } @article {pmid25759091, year = {2015}, author = {Hida, T and Hamasaki, M and Matsumoto, S and Abe, S and Takakura, K and Hiroshima, K and Nabeshima, K}, title = {Diffuse intrapulmonary malignant mesothelioma presenting with miliary pulmonary nodules: A case report.}, journal = {Pathology international}, volume = {65}, number = {6}, pages = {318-323}, doi = {10.1111/pin.12282}, pmid = {25759091}, issn = {1440-1827}, mesh = {Aged ; Antineoplastic Agents/*therapeutic use ; Asbestos/adverse effects ; Biopsy ; Cisplatin/therapeutic use ; Fatal Outcome ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Lung/pathology ; Lung Neoplasms/drug therapy/*pathology ; Male ; Mesothelioma/drug therapy/*pathology ; Mesothelioma, Malignant ; Pemetrexed/therapeutic use ; }, abstract = {A 67-year-old male with a history of asbestos exposure presented with fever, cough, and dyspnea and was found to have diffuse granular shadowing in both lungs, right pleural effusion, and hilar and mediastinal lymphadenopathy upon chest computed tomography. For definitive diagnosis, a thoracoscopic lung biopsy was performed. Intraoperative findings showed no remarkable macroscopic changes in the visceral and parietal pleura, although a high level of hyaluronic acid in the pleural effusion was noted. Histological findings showed proliferation of atypical cells with round-to-oval nuclei, prominent nucleoli, and eosinophilic cytoplasms. These cells were arranged into sheets or tubules and were located predominantly in the lung parenchyma. Lymphovascular invasion was conspicuous. Immunohistochemically, tumor cells were positive for calretinin, D2-40, and CK5/6, focally positive for Ber-EP4, but negative for WT-1, TTF-1, CEA, and MOC31. Fluorescence in situ hybridization for the tumor suppressor p16 revealed homozygous deletion in the tumor cells. Therefore, we diagnosed the tumor as diffuse intrapulmonary malignant mesothelioma (DIMM). The patient had a poor response to chemotherapy and died 1 year after diagnosis. Although rare, DIMM should be considered when patients present with multiple, tiny intrapulmonary nodules, regardless of macroscopic pleural changes. Furthermore, this is the first report on p16 status in DIMM.}, } @article {pmid25757056, year = {2015}, author = {Dragon, J and Thompson, J and MacPherson, M and Shukla, A}, title = {Differential Susceptibility of Human Pleural and Peritoneal Mesothelial Cells to Asbestos Exposure.}, journal = {Journal of cellular biochemistry}, volume = {116}, number = {8}, pages = {1540-1552}, pmid = {25757056}, issn = {1097-4644}, support = {P20 GM103449/GM/NIGMS NIH HHS/United States ; R01 ES021110/ES/NIEHS NIH HHS/United States ; }, mesh = {Adult ; Aged ; Asbestos, Crocidolite/*toxicity ; Cell Line ; Cell Survival/drug effects ; Female ; Gene Expression Regulation, Neoplastic/*drug effects ; Genetic Predisposition to Disease ; High-Throughput Nucleotide Sequencing ; Humans ; Inflammation/genetics ; Lung Neoplasms/chemically induced/*genetics/*pathology ; Male ; Mesothelioma/chemically induced/*genetics/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Peritoneal Neoplasms/chemically induced/*genetics/pathology ; Pleural Neoplasms/chemically induced/*genetics/pathology ; Sequence Analysis, RNA ; }, abstract = {Malignant mesothelioma (MM) is an aggressive cancer of mesothelial cells of pleural and peritoneal cavities. In 85% of cases both pleural and peritoneal MM is caused by asbestos exposure. Although both are asbestos-induced cancers, the incidence of pleural MM is significantly higher (85%) than peritoneal MM (15%). It has been proposed that carcinogenesis is a result of asbestos-induced inflammation but it is not clear what contributes to the differences observed between incidences of these two cancers. We hypothesize that the observed differences in incidences of pleural and peritoneal MM are the result of differences in the direct response of these cell types to asbestos rather than to differences mediated by the in vivo microenvironment. To test this hypothesis we characterized cellular responses to asbestos in a controlled environment. We found significantly greater changes in genome-wide expression in response to asbestos exposure in pleural mesothelial cells as compared to peritoneal mesothelial cells. In particular, a greater response in many common genes (IL-8, ATF3, CXCL2, CXCL3, IL-6, GOS2) was seen in pleural mesothelial cells as compared to peritoneal mesothelial cells. Unique genes expressed in pleural mesothelial cells were mainly pro-inflammatory (G-CSF, IL-1β, IL-1α, GREM1) and have previously been shown to be involved in development of MM. Our results are consistent with the hypothesis that differences in incidences of pleural and peritoneal MM upon exposure to asbestos are the result of differences in mesothelial cell physiology that lead to differences in the inflammatory response, which leads to cancer.}, } @article {pmid25756049, year = {2015}, author = {Ak, G and Tomaszek, SC and Kosari, F and Metintas, M and Jett, JR and Metintas, S and Yildirim, H and Dundar, E and Dong, J and Aubry, MC and Wigle, DA and Thomas, CF}, title = {MicroRNA and mRNA features of malignant pleural mesothelioma and benign asbestos-related pleural effusion.}, journal = {BioMed research international}, volume = {2015}, number = {}, pages = {635748}, pmid = {25756049}, issn = {2314-6141}, mesh = {Aged ; Aged, 80 and over ; Asbestos/toxicity ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/*genetics/pathology ; Male ; Mesothelioma/*genetics/pathology ; Mesothelioma, Malignant ; MicroRNAs/*biosynthesis/genetics ; Middle Aged ; Pleural Effusion/chemically induced/*genetics/pathology ; Proto-Oncogene Proteins c-met/biosynthesis/genetics ; RNA, Messenger/*biosynthesis/genetics ; }, abstract = {INTRODUCTION: We investigated the expression of microRNAs and mRNAs in pleural tissues from patients with either malignant pleural mesothelioma or benign asbestos-related pleural effusion.

METHODS: Fresh frozen tissues from a total of 18 malignant pleural mesothelioma and 6 benign asbestos-related pleural effusion patients were studied. Expression profiling of mRNA and microRNA was performed using standard protocols.

RESULTS: We discovered significant upregulation of multiple microRNAs in malignant pleural mesothelioma compared to benign asbestos-related pleural effusion. Hsa-miR-484, hsa-miR-320, hsa-let-7a, and hsa-miR-125a-5p were able to discriminate malignant from benign disease. Dynamically regulated mRNAs were also identified. MET was the most highly overexpressed gene in malignant pleural mesothelioma compared to benign asbestos-related pleural effusion. Integrated analyses examining microRNA-mRNA interactions suggested multiple altered targets within the Notch signaling pathway.

CONCLUSIONS: Specific microRNAs and mRNAs may have diagnostic utility in differentiating patients with malignant pleural mesothelioma from benign asbestos-related pleural effusion. These studies may be particularly helpful in patients who reside in a region with a high incidence of mesothelioma.}, } @article {pmid25754500, year = {2015}, author = {Krupoves, A and Camus, M and De Guire, L}, title = {Incidence of malignant mesothelioma of the pleura in Québec and Canada from 1984 to 2007, and projections from 2008 to 2032.}, journal = {American journal of industrial medicine}, volume = {58}, number = {5}, pages = {473-482}, doi = {10.1002/ajim.22442}, pmid = {25754500}, issn = {1097-0274}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Canada/epidemiology ; Carcinogens/*toxicity ; Cohort Studies ; Environmental Exposure/*adverse effects ; Female ; Forecasting ; Humans ; Incidence ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Diseases/*epidemiology/etiology ; Pleural Neoplasms/*epidemiology/etiology ; Poisson Distribution ; Quebec/epidemiology ; Registries ; }, abstract = {BACKGROUND: Continuous increase in male incidence of malignant mesothelioma of the pleura (MMP) despite the drop of asbestos production since 1980 in Québec motivated this study aiming to assess when the rates of MMP will decline.

METHODS: Age-standardized rates and trends were estimated over the 1984-2007 period by sex for Québec versus "Canada-excluding-Québec" (Can-Qc). An age-cohort regression was used to make projections for 2008-2032.

RESULTS: Average rates of MMP in Québec men and women were significantly higher than in Can-Qc. Projected rates peak between 2003 and 2012 in all four study populations and decline thereafter.

CONCLUSION: The higher MMP rates and observed/projected time patterns in Québec men are consistent with past asbestos production and occupational exposures. The excess in Québec women may also be explained by domestic and, for some, by neighborhood exposures. To pursue the decrease in MMP rates beyond 2032, efforts to reduce asbestos exposure should be maintained.}, } @article {pmid25749175, year = {2015}, author = {Faig, J and Howard, S and Levine, EA and Casselman, G and Hesdorffer, M and Ohar, JA}, title = {Changing pattern in malignant mesothelioma survival.}, journal = {Translational oncology}, volume = {8}, number = {1}, pages = {35-39}, pmid = {25749175}, issn = {1936-5233}, abstract = {UNLABELLED: Survival for mesothelioma has been shown to be poor, with marginal improvement over time. Recent advances in the understanding of pathophysiology and treatment of mesothelioma may impact therapy to improve survival that may not be evident from available clinical trials that are often small and not randomized. Therapies may affect survival differently based on mesothelioma location (pleural vs peritoneal). Data are conflicting regarding the effect of asbestos exposure on mesothelioma location.

OBJECTIVES: We examined survival in a large cohort of mesothelioma subjects analyzed by tumor location and presence and mode of asbestos exposure.

METHODS: Data were analyzed from cases (n = 380) diagnosed with mesothelioma from 1992 to 2012. Cases were either drawn from treatment referrals, independent medical evaluation for medical legal purposes, or volunteers who were diagnosed with mesothelioma. Subjects completed an occupational medical questionnaire, personal interview with the examining physician, and physician review of the medical record.

RESULTS: This study reports better survival for mesothelioma than historical reports. Survival for peritoneal mesothelioma was longer than that for pleural mesothelioma (hazard ratio = 0.36, 95% confidence interval = 0.24-0.54, P < .001) after adjusting for gender and age at diagnosis. Non-occupational cases were more likely to be 1) diagnosed with peritoneal mesothelioma, 2) female, 3) exposed, and 4) diagnosed at a younger age and to have a 5) shorter latency compared to occupational cases (P < .001).

CONCLUSION: Peritoneal mesothelioma was more likely associated with non-occupational exposure, thus emphasizing the importance of exposure history in enhancing early diagnosis and treatment impact.}, } @article {pmid25726562, year = {2015}, author = {Røe, OD and Stella, GM}, title = {Malignant pleural mesothelioma: history, controversy and future of a manmade epidemic.}, journal = {European respiratory review : an official journal of the European Respiratory Society}, volume = {24}, number = {135}, pages = {115-131}, pmid = {25726562}, issn = {1600-0617}, mesh = {Animals ; Asbestos ; Asbestosis/epidemiology/*history ; Biomarkers/analysis ; History, 18th Century ; History, 20th Century ; Humans ; *Lung Neoplasms/epidemiology/history/physiopathology ; *Mesothelioma/epidemiology/history/physiopathology ; Mesothelioma, Malignant ; Occupational Diseases/epidemiology/history ; Occupational Exposure ; *Pleural Neoplasms/epidemiology/history/physiopathology ; Poliovirus Vaccines/adverse effects ; Simian virus 40 ; Viral Vaccines/adverse effects ; }, abstract = {Asbestos is the term for a family of naturally occurring minerals that have been used on a small scale since ancient times. Industrialisation demanded increased mining and refining in the 20th century, and in 1960, Wagner, Sleggs and Marchand from South Africa linked asbestos to mesothelioma, paving the way to the current knowledge of the aetiology, epidemiology and biology of malignant pleural mesothelioma. Pleural mesothelioma is one of the most lethal cancers, with increasing incidence worldwide. This review will give some snapshots of the history of pleural mesothelioma discovery, and the body of epidemiological and biological research, including some of the controversies and unresolved questions. Translational research is currently unravelling novel circulating biomarkers for earlier diagnosis and novel treatment targets. Current breakthrough discoveries of clinically promising noninvasive biomarkers, such as the 13-protein signature, microRNAs and the BAP1 mesothelioma/cancer syndrome, are highlighted. The asbestos history is a lesson to not be repeated, but here we also review recent in vivo and in vitro studies showing that manmade carbon nanofibres could pose a similar danger to human health. This should be taken seriously by regulatory bodies to ensure thorough testing of novel materials before release in the society.}, } @article {pmid25724794, year = {2015}, author = {Lorkowski, J and Grzegorowska, O and Kotela, A and Weryński, W and Kotela, I}, title = {Shoulder ring complaints as a rare first symptom of malignant pleural mesothelioma.}, journal = {Advances in experimental medicine and biology}, volume = {852}, number = {}, pages = {5-10}, doi = {10.1007/5584_2015_113}, pmid = {25724794}, issn = {0065-2598}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos ; Asbestosis/epidemiology ; Female ; Humans ; Lung Neoplasms/*complications/*diagnosis/epidemiology ; Male ; Mesothelioma/*complications/*diagnosis/epidemiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/statistics & numerical data ; Pleural Neoplasms/*complications/*diagnosis/epidemiology ; Poland/epidemiology ; Radiography, Thoracic ; Retrospective Studies ; Shoulder Pain/*diagnosis/epidemiology/*etiology ; }, abstract = {The prevalence of malignant pleural mesothelioma is often encountered in the areas highly exposed to asbestos. The aim of this paper was a retrospective analysis of shoulder pain as a rare, first symptom of pleural mesothelioma, which constitutes an interdisciplinary diagnostic problem concerning both orthopedics and pulmonology. The research was based on a retrospective review of the patients' medical records. The considered period of time included the years 2006-2012. The study group included a total of 49 patients. Seven patients (14.3%) presented a complain of shoulder pain, as the first symptom of mesothelioma. The remaining 42 mesothelioma patients, without this symptom, constituted a reference group. The intensity of shoulder pain was, on average, 4/10 on an analog scale. A concomitant limitation of mobility was observed in five out of the seven subjects. In one case, limitation of motion and dysfunction of the shoulder joint were at an advanced stage. Neuralgia of upper limbs was found in two cases. We conclude that shoulder pain may be a manifesting symptom of malignant pleural mesothelioma. The neoplasm appears to have a pleiotropic effect on human body, reflected in different ways of its primary manifestation which may also include the motor system.}, } @article {pmid25722383, year = {2015}, author = {Stahel, RA and Weder, W and Felley-Bosco, E and Petrausch, U and Curioni-Fontecedro, A and Schmitt-Opitz, I and Peters, S}, title = {Searching for targets for the systemic therapy of mesothelioma.}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {26}, number = {8}, pages = {1649-1660}, doi = {10.1093/annonc/mdv101}, pmid = {25722383}, issn = {1569-8041}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Cisplatin/administration & dosage ; Everolimus/administration & dosage ; Focal Adhesion Protein-Tyrosine Kinases/antagonists & inhibitors/metabolism ; Humans ; Immunotherapy ; Lung Neoplasms/*drug therapy/metabolism ; Mesothelioma/*drug therapy/metabolism ; Mesothelioma, Malignant ; Molecular Targeted Therapy/*methods ; Pemetrexed/administration & dosage ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphoinositide-3 Kinase Inhibitors ; Pleural Neoplasms/*drug therapy/metabolism ; Protein Kinase Inhibitors/administration & dosage ; TOR Serine-Threonine Kinases/antagonists & inhibitors/metabolism ; }, abstract = {Malignant mesothelioma is an incurable disease associated with asbestos exposure arising in the pleural cavity and less frequently in the peritoneal cavity. Platinum-based combination chemotherapy with pemetrexed is the established standard of care. Multimodality approaches including surgery and radiotherapy are being investigated. Increasing knowledge about the molecular characteristics of mesothelioma had led to the identification of novel potential targets for systemic therapy. Current evidence suggests pathways activated in response to merlin deficiency, including Pi3K/mTOR and the focal adhesion kinase, as well as immunotherapeutic approaches to be most promising. This review elaborates on the rationale behind targeted approaches that have been and are undergoing exploration in mesothelioma and summarizes available clinical results and ongoing efforts to improve the systemic therapy of mesothelioma.}, } @article {pmid25712482, year = {2015}, author = {Welch, L and Dement, J and West, G}, title = {Mortality among sheet metal workers participating in a respiratory screening program.}, journal = {American journal of industrial medicine}, volume = {58}, number = {4}, pages = {378-391}, doi = {10.1002/ajim.22421}, pmid = {25712482}, issn = {1097-0274}, support = {OH009762/OH/NIOSH CDC HHS/United States ; }, mesh = {Asbestosis/mortality ; Canada/epidemiology ; Cause of Death ; Female ; Forced Expiratory Volume ; Humans ; Lung Neoplasms/diagnostic imaging/*mortality/physiopathology ; Male ; Mesothelioma/*mortality ; Metallurgy/*statistics & numerical data ; Middle Aged ; Occupational Diseases/*mortality ; Pleural Neoplasms/*mortality ; Pulmonary Disease, Chronic Obstructive/diagnostic imaging/*mortality ; Radiography ; Severity of Illness Index ; United States/epidemiology ; Vital Capacity ; }, abstract = {BACKGROUND: The Sheet Metal Occupational Health Institute Trust (SMOHIT) established a screening program in 1985 to examine the health hazards of the sheet metal industry in the U.S. and Canada.

METHODS: 17,345 individuals with over 20 years in the trade and who participated in the program were followed for causes of death between 1986 and 2010. Both SMRs and Cox proportional hazards models investigated predictors of death due to lung cancer, mesothelioma, and chronic obstructive pulmonary disease (COPD).

RESULTS: Significant excess mortality was seen for mesothelioma and asbestosis. Controlling for smoking, a strong trend for increasing lung cancer risk with increasing chest x-ray profusion >0/0 was observed. With an profusion score <1/0, FEV1 /FVC <80% was associated with lung cancer risk. COPD risk increased with increasing profusion score.

CONCLUSIONS: This study demonstrates asbestos-related diseases among workers with largely indirect exposures and an increased lung cancer risk with low ILO scores.}, } @article {pmid25707292, year = {2015}, author = {Gopar-Nieto, R and Aguilar-Madrid, G and Sotelo-Martínez, L and Juárez-Pérez, CA and Kelly-García, J and Argote-Greene, L and Ochoa-Vázquez, MD and García-Bazán, EM and Ramírez-Pérez, J and Haro-García, L and Jiménez-Ramírez, C and Cabello-López, A}, title = {Malignant Pleural Mesothelioma: Accuracy of CT Against Immunohistochemical Test Among the Mexican Population.}, journal = {Archives of medical research}, volume = {46}, number = {2}, pages = {107-111}, doi = {10.1016/j.arcmed.2015.02.002}, pmid = {25707292}, issn = {1873-5487}, mesh = {Adenocarcinoma/diagnosis/*diagnostic imaging ; Adenocarcinoma of Lung ; Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Female ; Humans ; Immunohistochemistry/methods ; Incidence ; Lung/diagnostic imaging/pathology ; Lung Neoplasms/diagnosis/*diagnostic imaging ; Male ; Mediastinum/diagnostic imaging ; Mesothelioma/diagnosis/*diagnostic imaging ; Mesothelioma, Malignant ; Mexico ; Middle Aged ; Occupational Exposure ; Pleural Neoplasms/diagnosis/*diagnostic imaging ; Retrospective Studies ; Sensitivity and Specificity ; Tomography, X-Ray Computed/*methods ; }, abstract = {BACKGROUND AND AIMS: Malignant pleural mesothelioma (MPM) is associated with occupational and environmental exposure to asbestos. The incidence is expected to increase as the use of asbestos is not prohibited in many countries, such as in Mexico. We undertook this study to determine sensitivity, specificity, predictive values and likelihood ratios of computed tomography (CT) in a sample from Mexican population with suspected MPM and other pleuropulmonary diseases.

METHODS: CT films of 38 patients suspected of having MPM were analyzed. A single observer was blinded to MPM diagnoses. The frequencies of ten CT findings were identified. A cut-off point of ≥5 CT findings was established to determine high MPM probability. Sensitivity, specificity, predictive values and likelihood ratio of the CT against biopsy using immunohistochemical testing (IHC) for MPM were calculated.

RESULTS: Of the 38 patients, 31 had MPM and seven had lung adenocarcinoma. The five key findings were mediastinal pleural thickening 96.7% (n = 30), nodular pleural thickening 93.3% (n = 29), pleural mass 83.9% (n = 26), diminished lung 70.9% (n = 22) and contracted hemithorax 70.9% (n = 22). Sensitivity 96.8% (83.2-99.4), specificity 85.7% (42.2-97.6), positive likelihood ratio 6.7 (1.1-41.6), and negative likelihood ratio of 0.04 (0.01-0.2) were reported.

CONCLUSIONS: Sensitivity and specificity in this study was greater than previously reported, 96.8% and 85.7 vs. 93.2 and 65.6%, respectively. CT is an easily accessible and useful tool that should be incorporated into the medical education of general physicians to improve MPM diagnosis of suspected cases.}, } @article {pmid25701019, year = {2015}, author = {Chellini, E and Martino, G and Grillo, A and Fedi, A and Martini, A and Indiani, L and Mauro, L}, title = {Malignant mesotheliomas in textile rag sorters.}, journal = {The Annals of occupational hygiene}, volume = {59}, number = {5}, pages = {547-553}, doi = {10.1093/annhyg/meu114}, pmid = {25701019}, issn = {1475-3162}, mesh = {Aged ; Asbestos/adverse effects ; Female ; Humans ; Italy/epidemiology ; Lung Neoplasms/epidemiology/*etiology ; Male ; Mesothelioma/epidemiology/*etiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Diseases/epidemiology/*etiology ; Occupational Exposure/adverse effects ; *Textile Industry ; }, abstract = {OBJECTIVES: To analyse the asbestos exposure characteristics and mesothelioma trend in textile workers operating in the larger Tuscan textile industrial province of Prato between 1988 and 2012.

METHODS: All cases of textile workers recorded by the Tuscan mesothelioma register are considered. The demographic and clinical characteristics and asbestos exposure of cases working in the province of Prato are examined. Crude incidence rates between 1988 and 2012 and their 95% confidence intervals (CI) are calculated in rag sorters and other textile workers. The trends of standardized rates are also evaluated, as well as the sources of occupational asbestos exposure from occupational histories of cases affected by other asbestos-related diseases in rag sorters.

RESULTS: One hundred and seventy-two malignant mesotheliomas (MMs) have been diagnosed in textile workers in Tuscany. Among these, 46.5% were residents in the province of Prato at the time of diagnosis, half of whom working as rag sorters. All rag sorters with MM are classified as occupationally asbestos exposed, while 71.7% are other textile workers exposed to asbestos. The estimated crude incidence rate in rag sorters in Prato ranges from 74.1×100000 (95% CI: 52.5-101.8) to 166.8×100000 (95% CI: 118.1-229.0). The standardized rates in Prato rag sorters appeared higher throughout the 1990s while in other Prato textile workers the rates increased later on, at the very end of the 1990s. Another 40 cases of asbestos-related diseases in rag sorters were also collected.

CONCLUSIONS: A very high incidence of MMs was observed in textile workers in Prato, especially among rag sorters. This result, together with the high number of other asbestos-related diseases in rag sorters, strongly supports the hypothesis of diffuse asbestos exposure in rag sorting, in the absence of any other relevant aetiological factor for malignant mesothelioma.}, } @article {pmid25683976, year = {2015}, author = {Demirer, E and Ghattas, CF and Radwan, MO and Elamin, EM}, title = {Clinical and prognostic features of erionite-induced malignant mesothelioma.}, journal = {Yonsei medical journal}, volume = {56}, number = {2}, pages = {311-323}, pmid = {25683976}, issn = {1976-2437}, mesh = {Adult ; Asbestos/*adverse effects ; Asbestos, Amphibole ; Environmental Exposure/*adverse effects ; Female ; Humans ; Lung Neoplasms/*chemically induced/diagnostic imaging ; Male ; Mesothelioma/*chemically induced/diagnostic imaging ; Mesothelioma, Malignant ; Middle Aged ; Pleura/diagnostic imaging ; Pleural Effusion/diagnostic imaging ; Pleural Neoplasms/*chemically induced/diagnostic imaging ; Prognosis ; Prospective Studies ; Retrospective Studies ; Tomography, X-Ray Computed ; Zeolites/*adverse effects ; }, abstract = {This review analytically examines the published data for erionite-related malignant pleural mesothelioma (E-MPM) and any data to support a genetically predisposed mechanism to erionite fiber carcinogenesis. Adult patients of age ≥18 years with erionite-related pleural diseases and genetically predisposed mechanisms to erionite carcinogenesis were included, while exclusion criteria included asbestos- or tremolite-related pleural diseases. The search was limited to human studies though not limited to a specific timeframe. A total of 33 studies (31042 patients) including 22 retrospective studies, 6 prospective studies, and 5 case reports were reviewed. E-MPM developed in some subjects with high exposures to erionite, though not all. Chest CT was more reliable in detecting various pleural changes in E-MPM than chest X-ray, and pleural effusion was the most common finding in E-MPM cases, by both tests. Bronchoalveolar lavage remains a reliable and relatively less invasive technique. Chemotherapy with cisplatin and mitomycin can be administered either alone or following surgery. Erionite has been the culprit of numerous malignant mesothelioma cases in Europe and even in North America. Erionite has a higher degree of carcinogenicity with possible genetic transmission of erionite susceptibility in an autosomal dominant fashion. Therapeutic management for E-MPM remains very limited, and cure of the disease is extremely rare.}, } @article {pmid25669666, year = {2015}, author = {Rena, O and Boldorini, R and Papalia, E and Mezzapelle, R and Baietto, G and Roncon, A and Casadio, C}, title = {Persistent lung expansion after pleural talc poudrage in non-surgically resected malignant pleural mesothelioma.}, journal = {The Annals of thoracic surgery}, volume = {99}, number = {4}, pages = {1177-1183}, doi = {10.1016/j.athoracsur.2014.11.050}, pmid = {25669666}, issn = {1552-6259}, mesh = {Aged ; Antineoplastic Combined Chemotherapy Protocols/*administration & dosage ; Biopsy, Needle ; Cohort Studies ; Confidence Intervals ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lung Neoplasms/diagnostic imaging/mortality/pathology/*therapy ; Male ; Mesothelioma/diagnostic imaging/mortality/pathology/*therapy ; Mesothelioma, Malignant ; Middle Aged ; Multivariate Analysis ; Neoplasm Staging ; Pleural Neoplasms/diagnostic imaging/mortality/parasitology/*therapy ; Pleurodesis/*methods/mortality ; Radiography ; Retrospective Studies ; Risk Assessment ; Survival Analysis ; Talc/*administration & dosage ; Thoracic Surgery, Video-Assisted/methods ; Tissue Expansion/methods ; Treatment Outcome ; }, abstract = {BACKGROUND: To investigate the prognostic effect of persistent lung expansion after pleural talcage and other variables in non-surgically resected malignant pleural mesothelioma (MPM) patients.

METHODS: All consecutive patients submitted to video-assisted thoracoscopic (VAT) pleurodesis by talc poudrage for MPM between 2006 and 2011 were studied. The following parameters were prospectively recorded: age; sex; smoking history; asbestos exposure; C-reactive protein (CRP) levels; platelet (PLT) count; Eastern Cooperative Oncology Group performance status (ECOG PS); histologic subtype; clinical stage (cStage); chemotherapy; pleural fluid volume; and persistence of lung expansion at 3 months follow-up. Survival was assessed in June 2013.

RESULTS: A total of 172 patients were considered; 146 of 172 patients demonstrated a complete lung expansion at discharge, whereas only 85 of 172 patients had persistent expanded lung on the affected side at the 3-month follow-up chest x-ray. Median survival was 11.5 months (95% confidence interval [CI], 10% to 14%) and 2-year disease-specific survival was 13% (95% CI, 7% to 24%) for the entire cohort. Multivariate analysis showed that non-epithelioid histology (hazard ratio [HR], 2.81; 95% CI, 1.82% to 5.09%), pleural fluid recurrence (HR 2.54; 95% CI, 1.73% to 4.40%), cStage greater than II (HR 2.36; 95% CI, 1.50% to 4.32%), ECOG PS greater than 1 (HR 2.19; 95% CI, 1.26% to 4.23%), CRP greater than 5 mg/L (HR 2.01; 95% CI, 1.18% to 4.12%), and PLT count greater than 400,000 (HR 1.76; 95% CI 1.14% to 3.92%) were independent predictors of poor prognosis.

CONCLUSIONS: Persistent lung expansion after pleural talc poudrage and absence of fluid recurrence is demonstrated to be a stronger factor in predicting survival rather than clinical stage and other clinical variables in not surgically resected MPM patients.}, } @article {pmid25668121, year = {2015}, author = {Baumann, F and Buck, BJ and Metcalf, RV and McLaurin, BT and Merkler, DJ and Carbone, M}, title = {The Presence of Asbestos in the Natural Environment is Likely Related to Mesothelioma in Young Individuals and Women from Southern Nevada.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {10}, number = {5}, pages = {731-737}, pmid = {25668121}, issn = {1556-1380}, support = {P01 CA114047/CA/NCI NIH HHS/United States ; P01CA114047/CA/NCI NIH HHS/United States ; R01CA106567/CA/NCI NIH HHS/United States ; P30CA071789/CA/NCI NIH HHS/United States ; R01 CA106567/CA/NCI NIH HHS/United States ; P30 CA071789/CA/NCI NIH HHS/United States ; }, mesh = {Age Factors ; Asbestos/*analysis ; Environmental Exposure/*analysis ; Female ; Geology ; Humans ; Incidence ; *Inhalation Exposure ; Male ; Mesothelioma/*epidemiology/mortality ; Middle Aged ; Nevada/epidemiology ; Sex Factors ; Weather ; }, abstract = {BACKGROUND: Inhalation of asbestos and other mineral fibers is known causes of malignant mesothelioma (MM) and lung cancers. In a setting of occupational exposure to asbestos, MM occurs four to eight times more frequently in men than in women, at the median age of 74 years, whereas an environmental exposure to asbestos causes the same number of MMs in men and women, at younger ages.

METHODS: We studied the geology of Nevada to identify mineral fibers in the environment. We compared MM mortality in different Nevada counties, per sex and age group, for the 1999 to 2010 period.

RESULTS: We identified the presence of carcinogenic minerals in Nevada, including actinolite asbestos, erionite, winchite, magnesioriebeckite, and richterite. We discovered that, compared with the United States and other Nevada counties, Clark and Nye counties, in southern Nevada, had a significantly higher proportion of MM that occurred in young individuals (<55 years) and in women.

CONCLUSIONS: The elevated percentage of women and individuals younger than 55 years old, combined with a sex ratio of 1:1 in this age group and the presence of naturally occurring asbestos, suggests that environmental exposure to mineral fibers in southern Nevada may be contributing to some of these mesotheliomas. Further research to assess environmental exposures should allow the development of strategies to minimize exposure, as the development of rural areas continues in Nevada, and to prevent MM and other asbestos-related diseases.}, } @article {pmid25633928, year = {2015}, author = {Dahlgren, J and Talbott, P}, title = {Case report: peritoneal mesothelioma from asbestos in hairdryers.}, journal = {International journal of occupational and environmental health}, volume = {21}, number = {1}, pages = {1-4}, pmid = {25633928}, issn = {2049-3967}, mesh = {*Asbestos ; Female ; Humans ; Lung Neoplasms/chemically induced/*diagnosis/epidemiology ; Mesothelioma/chemically induced/*diagnosis/epidemiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Diseases/chemically induced/*epidemiology ; *Occupational Exposure ; Peritoneal Neoplasms/chemically induced/*diagnosis/epidemiology ; Risk Assessment ; }, abstract = {BACKGROUND: The relationship between mesothelioma and exposure to asbestos is well established. As a result, the use of asbestos in buildings, construction sites, and mines, as well as the implications of disease for the workers has received considerable attention. However, asbestos was also used in household equipment and consumer products, including hairdryers.

PURPOSE: To examine one case of peritoneal mesothelioma in a hairdresser and review the relevant literature on asbestos exposure from hairdryers.

METHODS: The subject's medical and occupational records were obtained and reviewed and a physical examination was performed.

RESULTS: The results indicate that the subject developed peritoneal mesothelioma from her occupational exposure to asbestos containing hairdryers in accordance with the literature.

CONCLUSION: Hairdryers are possible sources of asbestos exposure in patients with mesothelioma, and the asbestos exposure risk is higher for those who use hairdryers occupationally.}, } @article {pmid25613098, year = {2015}, author = {Petersen, R and Petersen, JA and Mikkelsen, S}, title = {[Non-occupational pleural mesothelioma].}, journal = {Ugeskrift for laeger}, volume = {177}, number = {3}, pages = {V09140480}, pmid = {25613098}, issn = {1603-6824}, mesh = {Aged ; Asbestos/*adverse effects ; Humans ; Lung Neoplasms/*chemically induced ; Male ; Mesothelioma/*chemically induced ; Mesothelioma, Malignant ; Occupational Exposure/adverse effects ; Pleural Neoplasms/*chemically induced ; }, abstract = {Asbestos fibres is the only known cause of malignant mesothelioma (MM). The risk of MM is increased also by low and brief exposure. MM has a latency of 20-50 years. We report two cases of MM who were exposed to asbestos during do-it-yourself roof renovation including cutting and drilling in roof sheeting containing asbestos. A detailed occupational history revealed no occupational exposure. The two cases demonstrate the importance of careful handling of products containing asbestos, with emphasis on avoidance of inhaling asbestos fibres.}, } @article {pmid25604170, year = {2014}, author = {Flores-Franco, RA and Ramos-Martínez, E and Luévano-Flores, E and Fierro-Murga, R and Barriga-Acevedo, R and Martínez-Tapia, ME and Luévano-González, A and Gómez-Díaz, A and Perea-Sánchez, RA}, title = {Malignant mesothelioma trends in Chihuahua, Mexico.}, journal = {Salud publica de Mexico}, volume = {56}, number = {4}, pages = {315-316}, pmid = {25604170}, issn = {1606-7916}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Carcinoma, Bronchogenic/epidemiology ; Environmental Exposure ; Female ; Health Surveys ; Humans ; Lung Neoplasms/epidemiology ; Male ; Mesothelioma/*epidemiology ; Mexico ; Middle Aged ; Morbidity/trends ; Pleural Effusion/epidemiology ; Pleural Neoplasms/*epidemiology ; Sex Distribution ; Tuberculosis, Pleural/epidemiology ; }, } @article {pmid25598227, year = {2015}, author = {Tosun, AB and Yergiyev, O and Kolouri, S and Silverman, JF and Rohde, GK}, title = {Detection of malignant mesothelioma using nuclear structure of mesothelial cells in effusion cytology specimens.}, journal = {Cytometry. Part A : the journal of the International Society for Analytical Cytology}, volume = {87}, number = {4}, pages = {326-333}, pmid = {25598227}, issn = {1552-4930}, support = {P41 GM103712/GM/NIGMS NIH HHS/United States ; R01 GM090033/GM/NIGMS NIH HHS/United States ; R21 CA188938/CA/NCI NIH HHS/United States ; }, mesh = {Asbestos/adverse effects ; Cell Nucleus/*physiology ; Chromatin/physiology ; Cytodiagnosis/*methods ; Cytological Techniques/methods ; Epithelial Cells/pathology ; Humans ; Image Processing, Computer-Assisted ; Lung Neoplasms/*classification/*diagnosis ; Mesothelioma/*classification/*diagnosis ; Mesothelioma, Malignant ; Pleura/cytology/pathology ; Pleural Effusion, Malignant/*cytology/pathology ; }, abstract = {Mesothelioma is a form of cancer generally caused from previous exposure to asbestos. Although it was considered a rare neoplasm in the past, its incidence is increasing worldwide due to extensive use of asbestos. In the current practice of medicine, the gold standard for diagnosing mesothelioma is through a pleural biopsy with subsequent histologic examination of the tissue. The diagnostic tissue should demonstrate the invasion by the tumor and is obtained through thoracoscopy or open thoracotomy, both being highly invasive surgical operations. On the other hand, thoracocentesis, which is removal of effusion fluid from the pleural space, is a far less invasive procedure that can provide material for cytological examination. In this study, we aim at detecting and classifying malignant mesothelioma based on the nuclear chromatin distribution from digital images of mesothelial cells in effusion cytology specimens. Accordingly, a computerized method is developed to determine whether a set of nuclei belonging to a patient is benign or malignant. The quantification of chromatin distribution is performed by using the optimal transport-based linear embedding for segmented nuclei in combination with the modified Fisher discriminant analysis. Classification is then performed through a k-nearest neighborhood approach and a basic voting strategy. Our experiments on 34 different human cases result in 100% accurate predictions computed with blind cross validation. Experimental comparisons also show that the new method can significantly outperform standard numerical feature-type methods in terms of agreement with the clinical diagnosis gold standard. According to our results, we conclude that nuclear structure of mesothelial cells alone may contain enough information to separate malignant mesothelioma from benign mesothelial proliferations.}, } @article {pmid25586016, year = {2015}, author = {Guerriero, A and Giovenali, P and La Starza, R and Mecucci, C and Montesi, G and Pasquino, S and Pierini, T and Ragni, T and Sidoni, A}, title = {Metachronous cardiac and cerebral sarcomas: case report with focus on molecular findings and review of the literature.}, journal = {Human pathology}, volume = {46}, number = {3}, pages = {482-487}, doi = {10.1016/j.humpath.2014.10.028}, pmid = {25586016}, issn = {1532-8392}, mesh = {12E7 Antigen ; Antigens, CD/analysis ; Brain Neoplasms/chemistry/diagnosis/genetics/*pathology/therapy ; Cell Adhesion Molecules/analysis ; Combined Modality Therapy ; Fatal Outcome ; Gliosarcoma/chemistry/diagnosis/genetics/*pathology/therapy ; Heart Neoplasms/chemistry/diagnosis/genetics/*pathology/therapy ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasms, Second Primary/chemistry/diagnosis/*pathology/therapy ; Sarcoma/chemistry/diagnosis/genetics/*pathology/therapy ; Vimentin/analysis ; }, abstract = {Although multiple primary malignancies are relatively rare, they have increased in frequency over the last decades, partly because of advances in diagnosis and therapy. This report describes for the first time the case of a patient with past occupational exposure to asbestos and no family history of cancer who developed 2 rare primary malignancies: a cardiac sarcoma and a gliosarcoma 11 months later. Molecular-cytogenetic studies did not identify common lesions to these 2 rare metachronous sarcomas. The gliosarcoma was associated with monosomy 10 and underlying PTEN monoallelic loss, which has been recurrently observed. In the cardiac sarcoma, MDM2 amplification and CDKN2AB/9p21 biallelic deletion suggested intimal sarcoma. No causal relationship was found between cardiac sarcoma and asbestos exposure, although MDM2 abnormalities were linked to malignant mesothelioma.}, } @article {pmid25582747, year = {2015}, author = {Damiran, N and Davaajav, K and Erdenebayar, E and Gomboloi, B and Frank, AL}, title = {Mesothelioma in Mongolia: case report.}, journal = {International journal of occupational and environmental health}, volume = {21}, number = {2}, pages = {166-168}, pmid = {25582747}, issn = {2049-3967}, mesh = {Asbestos/*toxicity ; Fatal Outcome ; Female ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Mesothelioma, Malignant ; Middle Aged ; Mongolia ; Occupational Diseases/*etiology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*etiology ; *Power Plants ; }, abstract = {BACKGROUND: More than 80% of cases of mesothelioma worldwide have a history of asbestos exposure. In Mongolia, workers in coal burning thermal power plants (TPP) have widely utilized asbestos as an insulation material.

METHODS: We describe the case of a 47-year-old woman diagnosed with a malignant pleural mesothelioma. She worked in a TPP in Ulaanbaatar, Mongolia for 28 years.

RESULTS: A computer tomography (CT) scan showed a circumferential ring around her left lung, and tissues' samples had a biphasic variant of mesothelioma with epithelioid and sarcomatoid components.

DISCUSSION: This is the first reported case of mesothelioma in Mongolia. We expect additional cases of mesothelioma, as well as other asbestos related diseases, will be identified in the future. In order to properly track asbestos related diseases in the country, we recommend the creation of an asbestos related disease registry.}, } @article {pmid25572813, year = {2015}, author = {de Lima, VA and Sørensen, JB}, title = {Third-line chemotherapy with carboplatin, gemcitabine and liposomised doxorubicin for malignant pleural mesothelioma.}, journal = {Medical oncology (Northwood, London, England)}, volume = {32}, number = {2}, pages = {458}, pmid = {25572813}, issn = {1559-131X}, mesh = {Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Carboplatin/administration & dosage ; Deoxycytidine/administration & dosage/analogs & derivatives ; Disease-Free Survival ; Doxorubicin/administration & dosage/analogs & derivatives ; Female ; Humans ; Kaplan-Meier Estimate ; Male ; Mesothelioma/*drug therapy/mortality ; Middle Aged ; Neoplasms, Mesothelial/*drug therapy/mortality ; Pleural Neoplasms/*drug therapy/mortality ; Polyethylene Glycols/administration & dosage ; Retrospective Studies ; Salvage Therapy/*methods ; Gemcitabine ; }, abstract = {There is no well-defined standard third-line chemotherapy for advanced malignant pleural mesothelioma (MPM). However, combination of carboplatin, liposomised doxorubicin (Caelyx) and gemcitabine (CCG regimen) has revealed noteworthy activity when used as first-line treatment. The aim of this study is to assess efficacy and toxicity profile for patients with MPM receiving CCG regimen as a third-line treatment. Carboplatin (AUC 5), Caelyx (30 mg/m(2)) and Gemcitabine (1,000 mg/m(2)) day 1, together with Gemcitabine (800 mg/m(2)) day 8, were given in up to six cycles. Patients were unresectable, PS 0-2, and had previously received a first-line platinum-based regimen and either vinorelbine or pemetrexed as second line. Response to treatment was assessed by CT scan using Modified RECIST criteria for mesothelioma. Forty-three patients were treated between 2010 and 2014. Median age was 67 years (47-82), 72 % males, and 79 % had previous asbestos exposure. Ninety per cent had PS 0-1, 58 % had epitheloid subtype and 63 % IMIG stage IV. First-line treatment was platinum and pemetrexed in 42 cases. Second-line treatment was vinorelbine in 42 cases and pemetrexed in one patient. Median lead time from cessation of second-line treatment to start of third CCG was 1 month. Twenty-eight per cent of the patients received six cycles, while treatment was postponed due to toxicities, mainly haematological, in 56 % of cases. No toxicity-related deaths occurred. Partial response (PR) occurred in 14 %, and disease control rate (DCR) was 60 %. Medians of overall survival (OS) from diagnosis and from start of CCG treatment were 25.2 months (18.4-31.5 months) and 6.8 months (5.4-8.4 months), respectively. Progression-free survival (PFS) was 4.1 months (1.7-4.5 months). Third-line CCG revealed a noteworthy efficacy with a DCR of 60.4 %. It was, however, associated with considerable haematological toxicity. Less toxic and more active treatment options are clearly needed.}, } @article {pmid25568603, year = {2014}, author = {Bianchi, C and Bianchi, T}, title = {Global mesothelioma epidemic: Trend and features.}, journal = {Indian journal of occupational and environmental medicine}, volume = {18}, number = {2}, pages = {82-88}, pmid = {25568603}, issn = {0973-2284}, abstract = {BACKGROUND: Mesothelioma incidence has taken epidemic proportions in various countries. The trend of the epidemic remains undefined.

OBJECTIVE: To collect the most recent available data on mesothelioma incidence in order to determine the present trend of the epidemic.

MATERIALS AND METHODS: Data of the Cancer and Mesothelioma Registries have been reviewed. In addition, numerous researchers were contacted to obtain supplementary information.

RESULTS: The highest incidence rates are reported from some countries in Europe (United Kingdom, The Netherlands, Malta, Belgium), and in Oceania (Australia, New Zealand). Relatively low incidence/mortality rates are reported from Japan and from Central Europe. In many countries a trend to increase continues to be observed. Data are not available for the mostly populous countries.

CONCLUSION: Mesothelioma epidemic does not show signs of attenuation. The lack of data for a large majority of the world does not allow that the consciousness of the risks related to asbestos exposure is reached.}, } @article {pmid25560527, year = {2015}, author = {Tsukamoto, Y and Hao, H and Kajimoto, N and Katayama, A and Suzuki, C and Terada, T and Nakano, T and Hanaoka, K and Hirota, S}, title = {Sarcomatoid pleural mesothelioma with osteosarcomatous, chondrosarcomatous and rhabdomyoblastic elements: an extremely rare autopsy case.}, journal = {Pathology international}, volume = {65}, number = {1}, pages = {51-53}, doi = {10.1111/pin.12226}, pmid = {25560527}, issn = {1440-1827}, mesh = {Aged ; Asbestos/adverse effects ; Autopsy ; Humans ; Male ; Mesothelioma/*pathology ; Neoplasms, Complex and Mixed/*pathology ; Occupational Exposure/adverse effects ; Pleural Neoplasms/*pathology ; Smoking/adverse effects ; }, } @article {pmid25559791, year = {2015}, author = {Sen, D}, title = {Working with asbestos and the possible health risks.}, journal = {Occupational medicine (Oxford, England)}, volume = {65}, number = {1}, pages = {6-14}, doi = {10.1093/occmed/kqu175}, pmid = {25559791}, issn = {1471-8405}, mesh = {Asbestos/*adverse effects ; Asbestosis/complications/diagnosis/*epidemiology ; *Health Status Indicators ; Humans ; Occupational Exposure/adverse effects/*legislation & jurisprudence/*statistics & numerical data ; Occupations/trends ; Work/standards/statistics & numerical data/trends ; }, abstract = {BACKGROUND: The generic term asbestos refers to a group of crystalline mineral silicates that occur naturally in various forms. Because of their properties of strength, heat and electrical resistance and their ability to withstand corrosion by acids and sea water, asbestos was used extensively both in the UK and worldwide.

AIMS: To provide a historical perspective of this ubiquitous occupational hazard, consider the key changes in UK legislation aimed at improving the management of this occupational health risk and describe the evidence from the scientific literature concerning asbestos and disease.

METHODS: Original articles, reviews (including reference textbooks) and scientific literature in PubMed and other principal medical science databases, 1960-2014, were searched. Publications by regulatory agencies and by governmental organizations were also considered and included where relevant.

RESULTS: Asbestos remains the biggest cause of cancer deaths worldwide. For malignant mesothelioma deaths alone, it is estimated that in the UK, between 2015 and 2020, the number of cases will peak at 2500 cases annually. It is not clear whether there is a safe level of asbestos fibres in air. Evidence for the efficacy of health surveillance is lacking.

CONCLUSIONS: Although the use of asbestos was banned in the UK in 1985 (amosite and crocidolite) and 1999 (chrysotile), it remains a significant occupational risk factor for work-related morbidity and mortality, causing both benign and malignant diseases, often with long latency. Further research is needed regarding exposure levels and health surveillance.}, } @article {pmid25558735, year = {2014}, author = {Binazzi, A and Scarselli, A and Massari, S and Bonafede, M and Corfiati, M and Di Marzio, D and Iavicoli, S and Marinaccio, A}, title = {[Active research, registration, and prevention of tumors of professional origin].}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {36}, number = {4}, pages = {360-364}, pmid = {25558735}, issn = {1592-7830}, mesh = {Asbestos/adverse effects ; Biomedical Research ; Carcinogens/toxicity ; Data Collection ; Government Agencies ; Humans ; Italy/epidemiology ; Mesothelioma/epidemiology/etiology/prevention & control ; National Health Programs/organization & administration ; Neoplasms/*epidemiology/etiology/prevention & control ; Occupational Diseases/*epidemiology/etiology/prevention & control ; Occupational Exposure ; *Population Surveillance ; *Registries ; Workers' Compensation/organization & administration ; }, abstract = {Occupational cancer is an important public health concern in Italy and in many industrialized countries. The difficulties in monitoring and the complexity in retrieving occupational cancer cases have required the enrolment of a national epidemiologic sureveillance system at national scale with active search methods. A structured system for the registration of occupational cancer cases is normed by the Decree No. 81/2008, that accounts for the previous legislative procedures and experiences. Research activities and prevention of occupational cancer should be integrated with insurance policies to the purpose of an efficient protection of workers health.}, } @article {pmid25557874, year = {2015}, author = {Tamminen, JA and Yin, M and Rönty, M and Sutinen, E and Pasternack, A and Ritvos, O and Myllärniemi, M and Koli, K}, title = {Overexpression of activin-A and -B in malignant mesothelioma - attenuated Smad3 signaling responses and ERK activation promote cell migration and invasive growth.}, journal = {Experimental cell research}, volume = {332}, number = {1}, pages = {102-115}, doi = {10.1016/j.yexcr.2014.12.010}, pmid = {25557874}, issn = {1090-2422}, mesh = {Activin Receptors, Type I/metabolism ; Activin Receptors, Type II/metabolism ; Activins/genetics/*metabolism ; Aged ; *Cell Movement ; Enzyme Activation ; Extracellular Signal-Regulated MAP Kinases/*metabolism ; Female ; Gene Expression ; Humans ; Lung Neoplasms/*metabolism/pathology ; MAP Kinase Signaling System ; Male ; Mesothelioma/*metabolism/pathology ; Mesothelioma, Malignant ; Middle Aged ; Neoplasm Invasiveness ; Smad3 Protein/*metabolism ; }, abstract = {Activin-A and activin-B, members of the TGF-β superfamily, are regulators of reproductive functions, inflammation and wound healing. These dimeric molecules regulate various cellular activities such as proliferation, migration and suvival. Malignant mesothelioma is an asbestos exposure related tumor affecting mainly pleura and it usually has a dismal prognosis. Here, we demonstrate that both activin-A and -B are abundantly expressed in mesothelioma tumor tissue as well as in cultured primary and established mesothelioma cells. Migratory and invasive mesothelioma cells were also found to have attenuated activation of the Smad2/3 pathway in response to activins. Migration and invasive growth of the cells in three-dimentional matrix was prevented by inhibition of activin activity using a soluble activin receptor 2B (sActR2B-Fc). This was associated with decreased ERK activity. Furthermore, migration and invasive growth was significantly inhibited by blocking ERK phosphorylation. Mesothelioma tumors are locally invasive and our results clearly suggest that acivins have a tumor-promoting function in mesothelioma through increasing expression and switching from canonical Smad3 pathway to non-canonical ERK pathway signaling. Blocking activin activity offers a new therapeutic approach for inhibition of mesothelioma invasive growth.}, } @article {pmid25549453, year = {2014}, author = {Amanbekova, AU and Sakiev, KZ and Ibraeva, LK and Otarbaeva, MB}, title = {[Main results of research concerning asbestos-related diseases in Kazakhstan Republic].}, journal = {Meditsina truda i promyshlennaia ekologiia}, volume = {}, number = {8}, pages = {13-18}, pmid = {25549453}, issn = {1026-9428}, mesh = {Asbestos/*adverse effects ; *Asbestosis/diagnosis/epidemiology/etiology/prevention & control ; Environmental Health/methods/standards ; Humans ; Kazakhstan/epidemiology ; *Lung Neoplasms/diagnosis/epidemiology/etiology/prevention & control ; *Mesothelioma/diagnosis/epidemiology/etiology/prevention & control ; Needs Assessment ; *Occupational Exposure/adverse effects/analysis/prevention & control ; Occupational Health Services/methods/organization & administration ; Preventive Health Services/methods/organization & administration ; }, abstract = {Problem of safety in asbestos usage attracts close attention of specialists and agencies responsible for public health preservation nowadays. According to European researchers, studies of uncontrolled usage of amphibole asbestos demonstrate high risk of asbestosis, lung cander and pleural mesothelioma among the workers and population exposed. The article covers results of research concerning influence of chrysotile asbestos on the workers, problems of asbestos-related diseases formation. The authors defined suggestions on a concept of controlled usage of chrysotile asbestos in Kazakhstan Republic.}, } @article {pmid25544756, year = {2015}, author = {Lim, CB and Prêle, CM and Baltic, S and Arthur, PG and Creaney, J and Watkins, DN and Thompson, PJ and Mutsaers, SE}, title = {Mitochondria-derived reactive oxygen species drive GANT61-induced mesothelioma cell apoptosis.}, journal = {Oncotarget}, volume = {6}, number = {3}, pages = {1519-1530}, pmid = {25544756}, issn = {1949-2553}, mesh = {Apoptosis/drug effects ; Cell Cycle Checkpoints/drug effects ; Cell Line, Tumor ; G1 Phase/drug effects ; HCT116 Cells ; HT29 Cells ; Humans ; Lung Neoplasms/*drug therapy/genetics/*metabolism/pathology ; Mesothelioma/*drug therapy/genetics/*metabolism/pathology ; Mesothelioma, Malignant ; Mitochondria/drug effects/*metabolism ; Oxidative Stress/drug effects/physiology ; Pyridines/*pharmacology ; Pyrimidines/*pharmacology ; Reactive Oxygen Species/*metabolism ; Transcription Factors/metabolism ; Zinc Finger Protein GLI1 ; }, abstract = {Gli transcription factors of the Hedgehog (Hh) pathway have been reported to be drivers of malignant mesothelioma (MMe) cell survival. The Gli inhibitor GANT61 induces apoptosis in various cancer cell models, and has been associated directly with Gli inhibition. However various chemotherapeutics can induce cell death through generation of reactive oxygen species (ROS) but whether ROS mediates GANT61-induced apoptosis is unknown. In this study human MMe cells were treated with GANT61 and the mechanisms regulating cell death investigated. Exposure of MMe cells to GANT61 led to G1 phase arrest and apoptosis, which involved ROS but not its purported targets, GLI1 or GLI2. GANT61 triggered ROS generation and quenching of ROS protected MMe cells from GANT61-induced apoptosis. Furthermore, we demonstrated that mitochondria are important in mediating GANT61 effects: (1) ROS production and apoptosis were blocked by mitochondrial inhibitor rotenone; (2) GANT61 promoted superoxide formation in mitochondria; and (3) mitochondrial DNA-deficient LO68 cells failed to induce superoxide, and were more resistant to apoptosis induced by GANT61 than wild-type cells. Our data demonstrate for the first time that GANT61 induces apoptosis by promoting mitochondrial superoxide generation independent of Gli inhibition, and highlights the therapeutic potential of mitochondrial ROS-mediated anticancer drugs in MMe.}, } @article {pmid25530474, year = {2015}, author = {Li, P and Liu, T and Kamp, DW and Lin, Z and Wang, Y and Li, D and Yang, L and He, H and Liu, G}, title = {The c-Jun N-terminal kinase signaling pathway mediates chrysotile asbestos-induced alveolar epithelial cell apoptosis.}, journal = {Molecular medicine reports}, volume = {11}, number = {5}, pages = {3626-3634}, pmid = {25530474}, issn = {1791-3004}, support = {I01 BX000786/BX/BLRD VA/United States ; P30 CA060553/CA/NCI NIH HHS/United States ; R01 ES020357/ES/NIEHS NIH HHS/United States ; }, mesh = {Alveolar Epithelial Cells/*drug effects/*metabolism ; Apoptosis/*drug effects ; Asbestos, Serpentine/*pharmacology ; Caspase 9/metabolism ; Cell Line, Tumor ; Cell Survival/drug effects ; Humans ; JNK Mitogen-Activated Protein Kinases/*metabolism ; Poly(ADP-ribose) Polymerases/metabolism ; Proteolysis/drug effects ; Signal Transduction/*drug effects ; }, abstract = {Exposure to chrysotile asbestos exposure is associated with an increased risk of mortality in combination with pulmonary diseases including lung cancer, mesothelioma and asbestosis. Multiple mechanisms by which chrysotile asbestos fibers induce pulmonary disease have been identified, however the role of apoptosis in human lung alveolar epithelial cells (AEC) has not yet been fully explored. Accumulating evidence implicates AEC apoptosis as a crucial event in the development of both idiopathic pulmonary fibrosis and asbestosis. The aim of the present study was to determine whether chrysotile asbestos induces mitochondria‑regulated (intrinsic) AEC apoptosis and, if so, whether this induction occurs via the activation of mitogen‑activated protein kinases (MAPK). Human A549 bronchoalveolar carcinoma‑derived cells with alveolar epithelial type II‑like features were used. The present study showed that chrysotile asbestos induced a dose‑ and time‑dependent decrease in A549 cell viability, which was accompanied by the activation of the MAPK c‑Jun N‑terminal kinases (JNK), but not the MAPKs extracellular signal‑regulated kinase 1/2 and p38. Chrysotile asbestos was also shown to induce intrinsic AEC apoptosis, as evidenced by the upregulation of the pro‑apoptotic genes Bax and Bak, alongside the activation of caspase‑9, poly (ADP‑ribose) polymerase (PARP), and the release of cytochrome c. Furthermore, the specific JNK inhibitor SP600125 blocked chrysotile asbestos‑induced JNK activation and subsequent apoptosis, as assessed by both caspase‑9 cleavage and PARP activation. The results of the present study demonstrated that chrysotile asbestos induces intrinsic AEC apoptosis by a JNK‑dependent mechanism, and suggests a potential novel target for the modulation of chrysotile asbestos‑associated lung diseases.}, } @article {pmid25527013, year = {2014}, author = {Donahoe, L and Cho, J and de Perrot, M}, title = {Novel induction therapies for pleural mesothelioma.}, journal = {Seminars in thoracic and cardiovascular surgery}, volume = {26}, number = {3}, pages = {192-200}, doi = {10.1053/j.semtcvs.2014.08.003}, pmid = {25527013}, issn = {1532-9488}, mesh = {Chemotherapy, Adjuvant ; Humans ; Lung Neoplasms/mortality/pathology/*therapy ; Mesothelioma/mortality/pathology/*therapy ; Mesothelioma, Malignant ; *Neoadjuvant Therapy/adverse effects/mortality ; Pleural Neoplasms/mortality/pathology/*therapy ; *Pneumonectomy/adverse effects/mortality ; Radiotherapy, Adjuvant ; Treatment Outcome ; }, abstract = {Malignant mesothelioma is becoming increasingly common, and rates of diagnosis are expected to continue to increase in the coming years because of the extensive use of asbestos in industrialized countries and the long time interval between exposure and onset of disease. Although much research has been done on the optimal treatment for this disease, the overall prognosis remains grim. The main components of therapy are surgery, chemotherapy, and radiation therapy, but there is controversy in the literature about the optimal inclusion and sequencing of these treatments, as each has unique risk profiles. We have developed a new Surgery for Mesothelioma After Radiation Therapy protocol consisting of induction-accelerated hemithoracic radiation followed by extrapleural pneumonectomy. The rationale behind this protocol is to maximize both the tumoricidal and immunogenic potential of the radiotherapy while minimizing the radiation toxicity to the ipsilateral lung. Our initial trial demonstrated the feasibility of this approach and has shown encouraging results in patients with epithelial histology. In this article, we reviewed the current literature on induction chemotherapy for mesothelioma as well as described the Surgery for Mesothelioma After Radiation Therapy protocol and upcoming studies of novel induction therapies for mesothelioma.}, } @article {pmid25526639, year = {2014}, author = {Fujimoto, N and Ohnuma, K and Aoe, K and Hosono, O and Yamada, T and Kishimoto, T and Morimoto, C}, title = {Clinical significance of soluble CD26 in malignant pleural mesothelioma.}, journal = {PloS one}, volume = {9}, number = {12}, pages = {e115647}, pmid = {25526639}, issn = {1932-6203}, mesh = {Aged ; Biomarkers, Tumor/blood/*metabolism ; Diagnosis, Differential ; Dipeptidyl Peptidase 4/blood/*metabolism ; Female ; Humans ; Lung Neoplasms/blood/enzymology/*pathology ; Male ; Mesothelioma/blood/enzymology/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Pleura/*enzymology/pathology ; Pleural Neoplasms/blood/enzymology/*pathology ; Prognosis ; Survival Analysis ; }, abstract = {There is no established single diagnostic marker for malignant pleural mesothelioma (MPM). CD26 is a 110 kDa, multifunctional, membrane-bound glycoprotein that has dipeptidyl peptidase IV (DPPIV) enzyme activity. The aim of this study was to evaluate the clinical significance of soluble CD26 (sCD26) in patients with MPM. The study included 80 MPM patients, 79 subjects with past asbestos exposure (SPE), and 134 patients with other benign pleural diseases (OPD) that were included as a control group. sCD26 levels and DPPIV activity in serum and/or pleural fluid were determined using an ELISA kit. Serum sCD26 levels and DPPIV enzyme activity in patients with MPM were significantly decreased compared with those in the SPE group (P = 0.000). The level of serum sCD26 was significantly decreased in patients with advanced stages of MPM compared with those with earlier stages (P = 0.047). The median OS of patients with MPM who had higher DPPIV enzyme activity was significantly longer than that of those with lower DPPIV enzyme activity (P = 0.032). The sCD26 levels in the pleural fluid of MPM patients with an epithelioid subtype were significantly increased compared with the OPD cohort (P = 0.012). Moreover, DPPIV enzyme activity in the pleural fluid of patients with MPM with an epithelioid subtype were significantly increased compared with those in the OPD cohort (P = 0.009). Patients with MPM who had lower specific DPPIV activity, determined as DPPIV/sCD26, showed significantly prolonged survival compared with those with higher specific DPPIV activity (P = 0.028). Serum sCD26 and DPPIV enzyme activity appear to be useful biomarkers for differentiating patients with MPM from SPE. The sCD26 levels or DPPIV enzyme activity in pleural fluid appear to be biomarkers in patients with an epithelioid subtype of MPM. DPPIV activity in serum or pleural fluid appears to be predictive for the prognosis of patients with MPM.}, } @article {pmid25522071, year = {2014}, author = {Fazzo, L and Menegozzo, S and Soggiu, ME and De Santis, M and Santoro, M and Cozza, V and Brangi, A and Menegozzo, M and Comba, P}, title = {Mesothelioma incidence in the neighbourhood of an asbestos-cement plant located in a national priority contaminated site.}, journal = {Annali dell'Istituto superiore di sanita}, volume = {50}, number = {4}, pages = {322-327}, doi = {10.4415/ANN_14_04_05}, pmid = {25522071}, issn = {2384-8553}, mesh = {Adult ; Age of Onset ; Aged ; *Asbestos ; Environmental Exposure ; Environmental Pollution/*adverse effects ; Female ; Humans ; Incidence ; Industry ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Pleural Neoplasms/*epidemiology ; Sex Factors ; }, abstract = {BACKGROUND: An epidemic of asbestos-related disease is ongoing in most industrialized countries, mainly attributable to past occupational exposure but partly due to environmental exposure. In this perspective, the incidence of pleural mesothelioma close to a former asbestos-cement plant in a national contaminated site was estimated.

METHODS: The census-tracts interested by atmospheric dispersion of facilities in the contaminated site were identified. Two subareas with different estimated environmental asbestos impact were distinguished. An ecological study at micro-geographic level was performed. The standardized incidence ratios (SIR) for study area and the two subareas, in comparison with region and municipality were computed. The standardized incidence rate ratio (IRR) between the two subareas was computed.

RESULTS: Mesothelioma incidence in the study area was increased: 46 cases were observed with respect to 22.23 expected (SIR: 2.02). The increase was confirmed in analysis considering only the subjects without an occupationally exposure to asbestos: 19 cases among men (SIR = 2.48; 95% CI: 1.49-3.88); 11 case among women (SIR = 1.34; 95% CI: 0.67-2.40). The IRR between the two subareas is less than one in overall population considering all age-classes and of 3 fold (IRR = 3.14, 95% CI: 0.65-9.17) in the age-classes below 55 years.

CONCLUSIONS: The findings indicate an increased incidence of pleural mesothelioma in the neighbourhood of asbestos-cement plant, and a possible etiological contribution of asbestos environmental exposure in detected risks.}, } @article {pmid25512155, year = {2014}, author = {Hashim, D and Boffetta, P}, title = {Occupational and environmental exposures and cancers in developing countries.}, journal = {Annals of global health}, volume = {80}, number = {5}, pages = {393-411}, doi = {10.1016/j.aogh.2014.10.002}, pmid = {25512155}, issn = {2214-9996}, mesh = {Air Pollution, Indoor ; Arsenic ; Asbestos ; *Carcinogens ; *Developing Countries ; Environmental Exposure/statistics & numerical data ; Humans ; Neoplasms/*epidemiology ; Occupational Diseases/*epidemiology ; Occupational Exposure/*statistics & numerical data ; }, abstract = {BACKGROUND: Over the past few decades, there has been a decline in cancers attributable to environmental and occupational carcinogens of asbestos, arsenic, and indoor and outdoor air pollution in high-income countries. For low- to middle-income countries (LMICs), however, these exposures are likely to increase as industrialization expands and populations grow.

OBJECTIVE: The aim of this study was to review the evidence on the cancer risks and burdens of selected environmental and occupational exposures in less-developed economies.

FINDINGS: A causal association has been established between asbestos exposure and mesothelioma and lung cancer. For arsenic exposure, there is strong evidence of bladder, skin, lung, liver, and kidney cancer effects. Women are at the highest risk for lung cancer due to indoor air pollution exposure; however, the carcinogenic effect on the risk for cancer in children has not been studied in these countries. Cancer risks associated with ambient air pollution remain the least studied in LMICs, although reported exposures are higher than World Health Organization, European, and US standards. Although some associations between lung cancer and ambient air pollutants have been reported, studies in LMICs are weak or subject to exposure misclassification. For pulmonary cancers, tobacco smoking and respiratory diseases have a positive synergistic effect on cancer risks.

CONCLUSIONS: A precise quantification of the burden of human cancer attributable to environmental and occupational exposures in LMICs is uncertain. Although the prevalence of carcinogenic exposures has been reported to be high in many such countries, the effects of the exposures have not been studied due to varying country-specific limitations, some of which include lack of resources and government support.}, } @article {pmid25511276, year = {2014}, author = {Liang, Y and Sun, X and Zhang, H and Cheng, Y and Gao, Y and Guo, J}, title = {[A case report of malignant peritoneal mesothelioma caused by asbestos].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {32}, number = {9}, pages = {695-696}, pmid = {25511276}, issn = {1001-9391}, mesh = {Asbestos/*adverse effects ; Humans ; Lung Neoplasms/*chemically induced ; Mesothelioma/*chemically induced ; Mesothelioma, Malignant ; Peritoneal Neoplasms/*chemically induced ; }, } @article {pmid25506632, year = {2015}, author = {Cyphert, JM and Carlin, DJ and Nyska, A and Schladweiler, MC and Ledbetter, AD and Shannahan, JH and Kodavanti, UP and Gavett, SH}, title = {Comparative long-term toxicity of Libby amphibole and amosite asbestos in rats after single or multiple intratracheal exposures.}, journal = {Journal of toxicology and environmental health. Part A}, volume = {78}, number = {3}, pages = {151-165}, doi = {10.1080/15287394.2014.947455}, pmid = {25506632}, issn = {1528-7394}, support = {T32 ES007126/ES/NIEHS NIH HHS/United States ; }, mesh = {Air Pollutants, Occupational/*toxicity ; Animals ; Asbestos, Amosite/toxicity ; Asbestos, Amphibole/*toxicity ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Inflammation/chemically induced/pathology/physiopathology ; Lung/*drug effects/pathology/physiopathology ; Lung Neoplasms/chemically induced/pathology ; Male ; Mesothelioma/chemically induced/pathology ; Rats ; Rats, Inbred F344 ; Toxicity Tests, Acute ; Toxicity Tests, Chronic ; }, abstract = {In former mine workers of Libby, MT, exposure to amphibole-containing vermiculite was linked to increased rates of asbestosis, lung cancer, and mesothelioma. Although many studies showed adverse effects following exposure to Libby amphibole (LA; a mixture of winchite, richterite, and tremolite), little is known regarding the relative toxicity of LA compared to regulated asbestos, or regarding the risks associated with acute high-dose exposures relative to repeated low-dose exposures. In this study, pulmonary function, inflammation, and pathology were assessed after single or multiple intratracheal (IT) exposures of LA or a well-characterized amosite (AM) control fiber with equivalent fiber characteristics. Male F344 rats were exposed to an equivalent total mass dose (0.15, 0.5, 1.5, or 5 mg/rat) of LA or AM administered either as a single IT instillation, or as multiple IT instillations given every other week over a 13-wk period, and necropsied up to 20 mo after the initial IT. When comparing the two fiber types, in both studies LA resulted in greater acute neutrophilic inflammation and cellular toxicity than equal doses of AM, but long-term histopathological changes were approximately equivalent between fibers, suggesting that LA is at least as toxic as AM. In addition, although no dose-response relationship was discerned, mesothelioma or lung carcinomas were found after exposure to low and high dose levels of LA or AM in both studies. Conversely, when comparing studies, an equal mass dose given over multiple exposures instead of a single bolus resulted in greater chronic pathological changes in lung at lower doses, despite the initially weaker acute inflammatory response. Overall, these results suggest that there is a possibility of greater long-term pathological changes with repeated lower LA dose exposures, which more accurately simulates chronic environmental exposures.}, } @article {pmid25506370, year = {2014}, author = {Najmi, K and Khosravi, A and Seifi, S and Emami, H and Chaibakhsh, S and Radmand, G and Khodadad, K}, title = {Clinicopathologic and survival characteristics of malignant pleural mesothelioma registered in hospital cancer registry.}, journal = {Tanaffos}, volume = {13}, number = {2}, pages = {6-12}, pmid = {25506370}, issn = {1735-0344}, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare but fatal thoracic tumor, which in the majority of patients is caused by prolonged exposure to asbestos fibers. We aimed at presenting clinicopathological and treatment outcomes of 60 patients of MPM registered in our hospital cancer registry.

MATERIALS AND METHODS: Demographic characteristics of patients, exposure to asbestos, smoking habit, their clinicopathologic characteristics and survival analysis were described.

RESULTS: Sixty patients had MPM. Forty patients (66.7%) were men. The mean age of patients was 55.8±11 years. Chest pain and dyspnea were the most prevalent symptoms (31.7%, and 30%, respectively). Thirty-six (61.7%) patients reported asbestos exposure. The median survival and Progression free survival (PFS) were 10.5 months (0.95CI=9.22-11.78) and 7.57 months (0.95CI=5.68-9.45), respectively. In multivariate analysis, exposure to asbestos and epithelioid subtype significantly extended the survival time. Bilateral involvement, high blood level of LDH and platelet count ≥400,000 significantly shortened the overall survival.

CONCLUSION: MPM is still an important health problem in Iran. Given the aforementioned results, developing a national program to eliminate asbestos-related diseases according to the world health organization (WHO) recommendation is necessary.}, } @article {pmid25505814, year = {2014}, author = {Creaney, J and Segal, A and Olsen, N and Dick, IM and Musk, AW and Skates, SJ and Robinson, BW}, title = {Pleural fluid mesothelin as an adjunct to the diagnosis of pleural malignant mesothelioma.}, journal = {Disease markers}, volume = {2014}, number = {}, pages = {413946}, pmid = {25505814}, issn = {1875-8630}, support = {//Medical Research Council/United Kingdom ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Female ; GPI-Linked Proteins/*metabolism ; Humans ; Male ; Mesothelin ; Mesothelioma/diagnosis/*metabolism ; Middle Aged ; Pleural Effusion, Malignant/diagnosis/*metabolism ; Prospective Studies ; ROC Curve ; Young Adult ; }, abstract = {RATIONALE: The diagnosis of pleural malignant mesothelioma (MM) by effusion cytology may be difficult and is currently controversial. Effusion mesothelin levels are increased in patients with MM but the clinical role of this test is uncertain.

OBJECTIVES: To determine the clinical value of measuring mesothelin levels in pleural effusion supernatant to aid diagnosis of MM.

METHODS AND MEASUREMENTS: Pleural effusion samples were collected prospectively from 1331 consecutive patients. Mesothelin levels were determined by commercial ELISA in effusions and their relationship to concurrent pathology reporting and final clinical diagnosis was determined.

RESULTS: 2156 pleural effusion samples from 1331 individuals were analysed. The final clinical diagnosis was 183 MM, 436 non-MM malignancy, and 712 nonmalignant effusions. Effusion mesothelin had a sensitivity of 67% for MM at 95% specificity. Mesothelin was elevated in over 47% of MM cases in effusions obtained before definitive diagnosis of MM was established. In the setting of inconclusive effusion cytology, effusion mesothelin had a positive predictive value of 79% for MM and 94% for malignancy.

CONCLUSIONS: A mesothelin-positive pleural effusion, irrespective of the identification of malignant cells, indicates the likely presence of malignancy and adds weight to the clinical rationale for further investigation to establish a malignant diagnosis.}, } @article {pmid25501304, year = {2015}, author = {Deng, XB and Xiao, L and Wu, Y and Jin, F and Mossman, B and Testa, JR and Xiao, GH}, title = {Inhibition of mesothelioma cancer stem-like cells with adenovirus-mediated NK4 gene therapy.}, journal = {International journal of cancer}, volume = {137}, number = {2}, pages = {481-490}, pmid = {25501304}, issn = {1097-0215}, support = {P01 CA114047/CA/NCI NIH HHS/United States ; P30 ES013508/ES/NIEHS NIH HHS/United States ; CA-114047/CA/NCI NIH HHS/United States ; }, mesh = {Adenoviridae/*genetics ; Animals ; Blotting, Western ; Cell Line, Tumor ; Cell Survival/drug effects/genetics ; Genetic Therapy/*methods ; Genetic Vectors/genetics ; Hepatocyte Growth Factor/genetics/metabolism/*physiology ; Humans ; Indoles/pharmacology ; Lung Neoplasms/genetics/pathology/*therapy ; Mesothelioma/genetics/pathology/*therapy ; Mesothelioma, Malignant ; Mice, Nude ; Microscopy, Fluorescence ; Neoplastic Stem Cells/drug effects/*metabolism ; Phosphorylation/drug effects ; Proto-Oncogene Proteins c-met/metabolism ; Spheroids, Cellular/metabolism ; Sulfones/pharmacology ; Xenograft Model Antitumor Assays ; beta Catenin/metabolism ; }, abstract = {Malignant mesothelioma (MM) is a highly invasive and chemoresistant malignancy induced by asbestos fibers. NK4, a hepatocyte growth factor antagonist and angiogenesis inhibitor, consists of the N-terminal hairpin domain and four kringle domains of the α-chain of hepatocyte growth factor. The therapeutic potential of NK4 has been demonstrated in a variety of tumor types. However, the mechanisms by which NK4 inhibits tumor growth have not been well delineated. In this study, it is shown that the NK4 adenovirus (Ad-NK4) potently inhibits cell viability, invasiveness and tumorigenicity of human MM cells. Significantly, this study demonstrates for the first time that Ad-NK4 inhibits cancer stem-like cell (CSC) properties as assessed by spheroid formation assay, side population analysis and flow cytometric sorting of CD24 cells. In addition to inhibiting phosphorylation of Met and AKT, Ad-NK4 markedly suppressed the active form of β-catenin, a key mediator of both Wnt and AKT pathways. It is further demonstrated that expression of NK4 suppresses β-catenin nuclear localization and transcriptional activity. Intriguingly, the expression levels of Oct4 and Myc, two critical stem cell factors and downstream targets of β-catenin, were also diminished by Ad-NK4. Furthermore, the strong antitumor effect of NK4 was found to be linked to its ability to inhibit CSCs as revealed by immunohistochemical examination of tumor specimens from a mouse xenograft model of human MM. These findings suggest that NK4 acts as a CSC inhibitor by impeding Met/AKT/β-catenin signaling and holds promise for achieving durable therapeutic responses in MM by constraining the CSC component of these aggressive tumors.}, } @article {pmid25497279, year = {2015}, author = {Kirschner, MB and Cheng, YY and Armstrong, NJ and Lin, RC and Kao, SC and Linton, A and Klebe, S and McCaughan, BC and van Zandwijk, N and Reid, G}, title = {MiR-score: a novel 6-microRNA signature that predicts survival outcomes in patients with malignant pleural mesothelioma.}, journal = {Molecular oncology}, volume = {9}, number = {3}, pages = {715-726}, pmid = {25497279}, issn = {1878-0261}, mesh = {Adult ; Aged ; Aged, 80 and over ; Cohort Studies ; Female ; *Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Humans ; Kaplan-Meier Estimate ; Lung Neoplasms/*genetics/pathology/surgery ; Male ; Mesothelioma/*genetics/pathology/surgery ; Mesothelioma, Malignant ; MicroRNAs/*genetics/metabolism ; Middle Aged ; Multivariate Analysis ; Palliative Care ; Pneumonectomy ; Proportional Hazards Models ; Reproducibility of Results ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Prognosis of malignant pleural mesothelioma (MPM) is poor, and predicting the outcomes of treatment is difficult. Here we investigate the potential of microRNA expression to estimate prognosis of MPM patients.

METHODS: Candidate microRNAs from microarray profiling of tumor samples from 8 long (median: 53.7 months) and 8 short (median: 6.4 months) survivors following extrapleural pneumonectomy (EPP) were validated by RT-qPCR in 48 additional EPP samples. Kaplan-Meier log ranking was used to further explore the association between microRNA expression and overall survival (OS). Binary logistic regression was used to construct a microRNA signature (miR-Score) that was able to predict an OS of ≥20 months. Performance of the miR-Score was evaluated by receiver operating characteristic (ROC) curve analysis and validated in a series of 43 tumor samples from patients who underwent palliative surgery [pleurectomy/decortication (P/D)].

RESULTS: The miR-Score, using expression data of six microRNAs (miR-21-5p, -23a-3p, -30e-5p, -221-3p, -222-3p, and -31-5p), enabled prediction of long survival with an accuracy of 92.3% for EPP and 71.9% for palliative P/D. Hazard ratios for score-negative patients were 4.12 (95% CI: 2.03-8.37) for EPP and 1.93 (95% CI: 1.01-3.69) for P/D. Importantly, adding the miR-Score to a set of clinical selection criteria (histology, age, gender) increased predictive accuracy in the independent validation set from 76.3% for clinical factors only to 87.3%.

CONCLUSIONS: This study has identified a novel 6-microRNA signature (miR-Score) that can accurately predict prognosis of MPM patients.}, } @article {pmid25488749, year = {2015}, author = {Guo, G and Chmielecki, J and Goparaju, C and Heguy, A and Dolgalev, I and Carbone, M and Seepo, S and Meyerson, M and Pass, HI}, title = {Whole-exome sequencing reveals frequent genetic alterations in BAP1, NF2, CDKN2A, and CUL1 in malignant pleural mesothelioma.}, journal = {Cancer research}, volume = {75}, number = {2}, pages = {264-269}, doi = {10.1158/0008-5472.CAN-14-1008}, pmid = {25488749}, issn = {1538-7445}, support = {5U01CA111295-07/CA/NCI NIH HHS/United States ; U54HG003067/HG/NHGRI NIH HHS/United States ; }, mesh = {Cullin Proteins/*genetics ; Cyclin-Dependent Kinase Inhibitor p16/*genetics ; DNA Mutational Analysis ; DNA, Neoplasm/genetics ; Exome ; Gene Dosage ; Humans ; Mesothelioma/*genetics ; Mutation ; Neurofibromin 2/*genetics ; Pleural Neoplasms/*genetics ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive neoplasm associated with asbestos exposure. Although previous studies based on candidate gene approaches have identified important common somatic mutations in MPM, these studies have focused on small sets of genes and have provided a limited view of the genetic alterations underlying this disease. Here, we performed whole-exome sequencing on DNA from 22 MPMs and matched blood samples, and identified 517 somatic mutations across 490 mutated genes. Integrative analysis of mutations and somatic copy-number alterations revealed frequent genetic alterations in BAP1, NF2, CDKN2A, and CUL1. Our study presents the first unbiased view of the genomic basis of MPM.}, } @article {pmid25480441, year = {2015}, author = {Creaney, J and Robinson, BW}, title = {Author's response: Inconsistent results or inconsistent methods? A plea for standardisation of biomarker sampling in mesothelioma studies.}, journal = {Thorax}, volume = {70}, number = {4}, pages = {374-375}, doi = {10.1136/thoraxjnl-2014-206564}, pmid = {25480441}, issn = {1468-3296}, mesh = {Extracellular Matrix Proteins/*metabolism ; Female ; GPI-Linked Proteins/*metabolism ; Humans ; Lung Neoplasms/*metabolism ; Male ; Mesothelioma/*metabolism ; Pleural Neoplasms/*metabolism ; }, } @article {pmid25479300, year = {2014}, author = {Järvholm, B and Aström, E}, title = {The risk of lung cancer after cessation of asbestos exposure in construction workers using pleural malignant mesothelioma as a marker of exposure.}, journal = {Journal of occupational and environmental medicine}, volume = {56}, number = {12}, pages = {1297-1301}, pmid = {25479300}, issn = {1536-5948}, mesh = {Adult ; Aged ; Asbestos/*toxicity ; Biomarkers ; *Construction Industry ; Humans ; Incidence ; Lung Neoplasms/*epidemiology/etiology ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Diseases/*epidemiology/etiology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*epidemiology/etiology ; Prospective Studies ; Registries ; Risk Assessment ; Sweden/epidemiology ; }, abstract = {OBJECTIVE: To study the risk of lung cancer in heavily asbestos-exposed workers after the exposure to asbestos has ended.

METHODS: Lung cancer was studied in a cohort of 189,896 Swedish construction workers through a linkage with the Swedish Cancer Registry. Asbestos exposure was estimated by the incidence of malignant mesothelioma in the occupational group.

RESULTS: There were in total 2835 cases of lung cancer. Workers with heavy exposure to asbestos had an increased risk of lung cancer (relative risks = 1.74; 95% confidence interval, 1.25 to 2.41) before exposure ended and a similar risk to those with low exposure 20 years after the exposure had ceased (relative risks = 0.94; 95% confidence interval, 0.77 to 1.15).

CONCLUSIONS: Workers with heavy exposure to asbestos have a similar risk of lung cancer as persons with low or no exposure 20 years after the exposure has ended.}, } @article {pmid25475619, year = {2015}, author = {Ugolini, D and Bonassi, S and Cristaudo, A and Leoncini, G and Ratto, GB and Neri, M}, title = {Temporal trend, geographic distribution, and publication quality in asbestos research.}, journal = {Environmental science and pollution research international}, volume = {22}, number = {9}, pages = {6957-6967}, pmid = {25475619}, issn = {1614-7499}, mesh = {*Asbestos ; Australia ; *Bibliometrics ; Brazil ; Canada ; China ; Europe ; Humans ; Italy ; Journal Impact Factor ; Lung Neoplasms ; Neoplasms ; Occupational Diseases ; Publishing ; Research ; }, abstract = {Asbestos is a well-known cause of cancer and respiratory diseases. The aim of the current study was to investigate the scientific production in asbestos research evaluating temporal trend, geographic distribution, impact factor (IF) of published literature, and taking into account socioeconomic variables. The PubMed database was searched starting from 1970. Publication numbers and IF were evaluated as absolute values and after standardization by population and gross domestic product (GDP). Six thousand nine hundred seven articles related to asbestos were retrieved. Publications grew steeply in the 1970s, leveled off in the 1980s, decreased in the 1990s, and then increased again. Mesothelioma, lung neoplasms, and occupational diseases are the most commonly used keywords. In the period of 1988-2011, 4220 citations were retrieved, 3187 of whom had an impact factor. The US, Italy, and the UK were the most productive countries. European countries published about 20 % more asbestos-related articles than the US, although the latter reached a higher mean IF, ranking second after Australia. When the national scientific production (sum of IF) was compared taking into account socioeconomic variables, Australia and Scandinavian countries performed very well, opposite to all main asbestos producers like Russia, China, and Brazil (except for Canada). The American Journal of Industrial Medicine and the Italian La Medicina del Lavoro published the highest numbers of articles. This study provides the first bibliometric analysis of scientific production in asbestos research. Interest appears to be higher in selected countries, with strong national features, and is growing again in the new millennium.}, } @article {pmid25471750, year = {2014}, author = {Comertpay, S and Pastorino, S and Tanji, M and Mezzapelle, R and Strianese, O and Napolitano, A and Baumann, F and Weigel, T and Friedberg, J and Sugarbaker, P and Krausz, T and Wang, E and Powers, A and Gaudino, G and Kanodia, S and Pass, HI and Parsons, BL and Yang, H and Carbone, M}, title = {Evaluation of clonal origin of malignant mesothelioma.}, journal = {Journal of translational medicine}, volume = {12}, number = {}, pages = {301}, pmid = {25471750}, issn = {1479-5876}, support = {P01 CA114047/CA/NCI NIH HHS/United States ; P01CA114047/CA/NCI NIH HHS/United States ; R01CA106567/CA/NCI NIH HHS/United States ; R01 CA160715/CA/NCI NIH HHS/United States ; P30CA071789/CA/NCI NIH HHS/United States ; R01 CA106567/CA/NCI NIH HHS/United States ; R01CA160715-0A/CA/NCI NIH HHS/United States ; P30 CA071789/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Alleles ; Female ; Humans ; Mesothelioma/*pathology ; Middle Aged ; Receptors, Androgen/genetics ; }, abstract = {BACKGROUND: The hypothesis that most cancers are of monoclonal origin is often accepted as a fact in the scientific community. This dogma arose decades ago, primarily from the study of hematopoietic malignancies and sarcomas, which originate as monoclonal tumors. The possible clonal origin of malignant mesothelioma (MM) has not been investigated. Asbestos inhalation induces a chronic inflammatory response at sites of fiber deposition that may lead to malignant transformation after 30-50 years latency. As many mesothelial cells are simultaneously exposed to asbestos fibers and to asbestos-induced inflammation, it may be possible that more than one cell undergoes malignant transformation during the process that gives rise to MM, and result in a polyclonal malignancy.

METHODS AND RESULTS: To investigate the clonality patterns of MM, we used the HUMARA (Human Androgen Receptor) assay to examine 16 biopsies from 14 women MM patients. Out of 16 samples, one was non-informative due to skewed Lyonization in its normal adjacent tissue. Fourteen out of the 15 informative samples revealed two electrophoretically distinct methylated HUMARA alleles, the Corrected Allele Ratio (CR) calculated on the allele peak areas indicating polyclonal origin MM.

CONCLUSIONS: Our results show that MM originate as polyclonal tumors and suggest that the carcinogenic "field effect" of mineral fibers leads to several premalignant clones that give rise to these polyclonal malignancies.}, } @article {pmid25469901, year = {2014}, author = {Weber, DG and Casjens, S and Johnen, G and Bryk, O and Raiko, I and Pesch, B and Kollmeier, J and Bauer, TT and Brüning, T}, title = {Combination of MiR-103a-3p and mesothelin improves the biomarker performance of malignant mesothelioma diagnosis.}, journal = {PloS one}, volume = {9}, number = {12}, pages = {e114483}, pmid = {25469901}, issn = {1932-6203}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*blood ; GPI-Linked Proteins/*blood ; Humans ; Lung Neoplasms/blood/*diagnosis ; Male ; Mesothelin ; Mesothelioma/blood/*diagnosis ; Mesothelioma, Malignant ; MicroRNAs/*blood ; Middle Aged ; ROC Curve ; }, abstract = {BACKGROUND: For the detection of malignant mesothelioma no single biomarker with reasonable sensitivity and specificity has been described so far. Mesothelin, the most prominent blood-based biomarker, is characterized by high specificity but low sensitivity. It might be reasonable to combine biomarkers of different molecular classes in order to improve the overall performance. The aim of this study was to assess the performance of the combination of mesothelin and miR-103a-3p as blood-based biomarker for mesothelioma.

METHODS/PRINCIPAL FINDINGS: Mesothelin concentration in plasma and miR-103a-3p levels in the cellular blood fraction were analyzed in 43 male mesothelioma patients and 52 male controls formerly exposed to asbestos. For the discrimination of epithelioid and biphasic mesothelioma from asbestos-exposed controls mesothelin and miR-103a-3p showed 74% and 89% sensitivity and 85% and 63% specificity, respectively. For the combination of mesothelin and miR-103a-3p a sensitivity of 95% and a specificity of 81% were calculated.

CONCLUSIONS/SIGNIFICANCE: The results of this study show that the combination of mesothelin and miR-103a-3p improves the diagnostic performance of individual blood-based biomarker to detect malignant mesothelioma. The obtained results indicate that the use of biomarkers of different molecular classes might be a reasonable approach to assemble a biomarker panel.}, } @article {pmid25467107, year = {2015}, author = {Remon, J and Reguart, N and Corral, J and Lianes, P}, title = {Malignant pleural mesothelioma: new hope in the horizon with novel therapeutic strategies.}, journal = {Cancer treatment reviews}, volume = {41}, number = {1}, pages = {27-34}, doi = {10.1016/j.ctrv.2014.10.007}, pmid = {25467107}, issn = {1532-1967}, mesh = {Antineoplastic Agents/*therapeutic use ; Humans ; Lung Neoplasms/*drug therapy ; Mesothelioma/*drug therapy ; Mesothelioma, Malignant ; Pleural Neoplasms/*drug therapy ; Prognosis ; Treatment Outcome ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare but aggressive malignancy of the pleura, with a strong causal link to asbestos exposure. MPM incidence has been increasing in recent years and it is not expected to fall off in the next two decades. Prognosis of MPM patients is modest since the vast majority of patients are diagnosed at advanced stage and because platinum-based chemotherapy remains the cornerstone of treatment, with no standard second line treatment. Most current efforts to improve outcomes are based on a better understanding of the stromal compartment and deregulated pathways leading ultimately to the design of clinical trials based on novel therapeutic approaches such as immunotherapy or molecular-directed compounds. This review seeks to update the last clinical trials investigating novel agents in unresectable MPM.}, } @article {pmid25460485, year = {2014}, author = {Perysinakis, I and Nixon, AM and Spyridakis, I and Kakiopoulos, G and Zorzos, C and Margaris, I}, title = {Primary intrahepatic malignant epithelioid mesothelioma.}, journal = {International journal of surgery case reports}, volume = {5}, number = {12}, pages = {1098-1101}, pmid = {25460485}, issn = {2210-2612}, abstract = {INTRODUCTION: Primary malignant hepatic mesotheliomas are extremely rare. We report the case of a patient with primary intrahepatic malignant mesothelioma who was treated in our department.

PRESENTATION OF CASE: A 66-year old male patient was admitted to our department for the evaluation of anemia. An abdominal computed tomography scan revealed a large space occupying lesion in the right liver lobe.

DISCUSSION: The tumor was subsequently resected and a diagnosis of primary intrahepatic malignant mesothelioma was made after pathologic examination. The patient did not receive adjuvant therapy and is currently alive and free of disease, 36 months after the resection.

CONCLUSION: To our knowledge this is the eighth adult case of primary intrahepatic malignant mesothelioma reported in the literature. These tumors are rarely diagnosed preoperatively. Absence of previous asbestos exposure does not exclude malignant mesothelioma from the differential diagnosis. Proper surgical treatment may offer prolonged survival to the patient, without adjuvant therapy.}, } @article {pmid25459327, year = {2014}, author = {Pasetto, R and Terracini, B and Marsili, D and Comba, P}, title = {Occupational burden of asbestos-related cancer in Argentina, Brazil, Colombia, and Mexico.}, journal = {Annals of global health}, volume = {80}, number = {4}, pages = {263-268}, doi = {10.1016/j.aogh.2014.09.003}, pmid = {25459327}, issn = {2214-9996}, mesh = {Argentina/epidemiology ; Asbestos/*toxicity ; Brazil/epidemiology ; Carcinogens/*toxicity ; Colombia/epidemiology ; Female ; Humans ; Laryngeal Neoplasms/*mortality ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; Mexico/epidemiology ; Occupational Diseases/*mortality ; Occupational Exposure/*adverse effects ; Ovarian Neoplasms/*mortality ; }, abstract = {BACKGROUND: An estimate at the national level of the occupational cancer burden brought about by the industrial use of asbestos requires detailed routine information on such uses as well as on vital statistics of good quality. A causal association with asbestos exposure has been established for mesothelioma and cancers of the lung, larynx, and ovary.

OBJECTIVES: The aim of this study was to provide estimates of the occupational burden of asbestos-related cancer for the Latin American countries that are or have been the highest asbestos consumers in the region: Argentina, Brazil, Colombia, and Mexico.

METHODS: The burden of multifactorial cancers has been estimated through the approach suggested for the World Health Organization using the population attributable fraction. The following data were used: Proportion of workforce employed in each economic sector. Proportion of workers exposed to asbestos in each sector. Occupational turnover. Levels of exposure. Proportion of the population in the workforce. Relative risk for each considered disease for 1 or more levels of exposure. Data on the proportion of workers exposed to asbestos in each sector are not available for Latin American countries; therefore, data from the European CAREX database (carcinogen exposure database) were used.

FINDINGS: Using mortality data of the World Health Organization Health Statistics database for the year 2009 and applying the estimated values for population attributable fractions, the number of estimated deaths in 5 years for mesothelioma and for lung, larynx, and ovary cancers attributable to occupational asbestos exposures, were respectively 735, 233, 29, and 14 for Argentina; 340, 611, 68, and 43 for Brazil; 255, 97, 14, and 9 for Colombia, and 1075, 219, 18, and 22 for Mexico.

CONCLUSIONS: The limitations in compiling the estimates highlight the need for improvement in the quality of asbestos-related environmental and health data. Nevertheless, the figures are already usable to promote a ban on asbestos use.}, } @article {pmid25459324, year = {2014}, author = {Marsili, D and Comba, P and Pasetto, R and Terracini, B}, title = {International scientific cooperation on asbestos-related disease prevention in Latin America.}, journal = {Annals of global health}, volume = {80}, number = {4}, pages = {247-250}, doi = {10.1016/j.aogh.2014.09.002}, pmid = {25459324}, issn = {2214-9996}, mesh = {Asbestos/*toxicity ; Asbestosis/prevention & control ; Construction Materials ; Environmental Exposure/*prevention & control ; Humans ; *International Cooperation ; Latin America ; Mesothelioma/*prevention & control ; Pleural Neoplasms/*prevention & control ; }, } @article {pmid25454236, year = {2015}, author = {Mensi, C and Riboldi, L and De Matteis, S and Bertazzi, PA and Consonni, D}, title = {Impact of an asbestos cement factory on mesothelioma incidence: global assessment of effects of occupational, familial, and environmental exposure.}, journal = {Environment international}, volume = {74}, number = {}, pages = {191-199}, doi = {10.1016/j.envint.2014.10.016}, pmid = {25454236}, issn = {1873-6750}, mesh = {Aged ; Asbestos/*toxicity ; Carcinogens/*toxicity ; *Environmental Exposure ; Family Health ; Female ; Humans ; Incidence ; Industry ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology ; Mesothelioma, Malignant ; *Occupational Exposure ; }, abstract = {Few studies have examined the incidence of malignant mesothelioma (MM) associated with distinct sources of asbestos exposure (occupational, familial, or environmental). We assessed the impact of asbestos exposure-global and by source-on the incidence of MM in Broni, an Italian town in which an asbestos cement factory once operated (1932-1993). Based on data collected by the Lombardy Mesothelioma Registry, we calculated the number of observed and expected MM cases among workers, their cohabitants, and people living in the area in 2000-2011. We identified 147 MM cases (17.45 expected), 138 pleural and nine peritoneal, attributable to exposure to asbestos from the factory. Thirty-eight cases had past occupational exposure at the factory (2.33 expected), numbering 32 men (26 pleural, six peritoneal) and six women (four pleural, two peritoneal). In the families of the workers, there were 37 MM cases (4.23 expected), numbering five men (all pleural) and 32 women (31 pleural, one peritoneal). Among residents in Broni or in the adjacent/surrounding towns, there were 72 cases of pleural MM (10.89 expected), numbering 23 men and 49 women. The largest MM excess was found in the towns of Broni (48 observed, 3.68 expected) and Stradella (16 observed, 1.85 expected). This study documents the large impact of the asbestos cement factory, with about 130 excess MM cases in a 12-year period. The largest MM burden was among women, from non-occupational exposure. Almost half of the MM cases were attributable to environmental exposure.}, } @article {pmid25444537, year = {2015}, author = {Norbet, C and Joseph, A and Rossi, SS and Bhalla, S and Gutierrez, FR}, title = {Asbestos-related lung disease: a pictorial review.}, journal = {Current problems in diagnostic radiology}, volume = {44}, number = {4}, pages = {371-382}, doi = {10.1067/j.cpradiol.2014.10.002}, pmid = {25444537}, issn = {1535-6302}, mesh = {Asbestosis/*diagnosis/physiopathology ; *Diagnostic Imaging ; Disease Progression ; Humans ; Prognosis ; }, abstract = {Asbestos exposure can lead to a variety of adverse effects in the thorax. Although currently in the western world, levels of exposure are kept in check by strict regulations, history of previous asbestos exposure continues to have an effect on many, owing to the latent nature of the pathophysiological response of the body to the inhaled fibers. The adverse effects of asbestos generally fall under 3 categories: pleural disease, lung parenchymal disease, and neoplastic disease. Effects on the pleura include pleural effusions, plaques, and diffuse pleural thickening. In the parenchyma, rounded atelectasis, fibrotic bands, and asbestosis are observed. Differentiating asbestosis from other forms of interstitial lung diseases, such as idiopathic pulmonary fibrosis, usual interstitial pneumonia, smoking-related lung disease, and mixed interstitial lung diseases, is important because the prognosis, course of disease, and management of the patient should be tailored based on the specific etiology of the disease. In this review, imaging findings specific to asbestosis are discussed. Finally, exposure to asbestos can lead to neoplastic disease such as pleural mesothelioma, peritoneal mesothelioma, and bronchogenic carcinoma. The purpose of this article is to review the effects of asbestos exposure in the thorax, pathophysiology of these responses, and disease course. Particular emphasis is placed on the radiographic appearance of the disease, discussion of various imaging modalities and their utility, and the role of imaging in the management of patients with previous asbestos exposure and asbestos-related pulmonary disease.}, } @article {pmid25438686, year = {2014}, author = {Hsu, LN and Sung, MT and Chiang, PH}, title = {Paratesticular malignant mesothelioma in a patient exposed to asbestos for more than 50 years.}, journal = {The Kaohsiung journal of medical sciences}, volume = {30}, number = {10}, pages = {537-538}, doi = {10.1016/j.kjms.2014.02.004}, pmid = {25438686}, issn = {2410-8650}, mesh = {Humans ; Male ; Mesothelioma/*pathology ; Testicular Neoplasms/*pathology ; }, } @article {pmid25428276, year = {2015}, author = {Boelter, FW and Xia, Y and Dell, L}, title = {Comparative Risks of Cancer from Drywall Finishing Based on Stochastic Modeling of Cumulative Exposures to Respirable Dusts and Chrysotile Asbestos Fibers.}, journal = {Risk analysis : an official publication of the Society for Risk Analysis}, volume = {35}, number = {5}, pages = {859-871}, doi = {10.1111/risa.12297}, pmid = {25428276}, issn = {1539-6924}, mesh = {*Asbestos, Serpentine ; *Dust ; Humans ; Inhalation Exposure ; Neoplasms/*etiology ; *Occupational Exposure ; *Risk Assessment ; *Stochastic Processes ; }, abstract = {Sanding joint compounds is a dusty activity and exposures are not well characterized. Until the mid 1970s, asbestos-containing joint compounds were used by some people such that sanding could emit dust and asbestos fibers. We estimated the distribution of 8-h TWA concentrations and cumulative exposures to respirable dusts and chrysotile asbestos fibers for four worker groups: (1) drywall specialists, (2) generalists, (3) tradespersons who are bystanders to drywall finishing, and (4) do-it-yourselfers (DIYers). Data collected through a survey of experienced contractors, direct field observations, and literature were used to develop prototypical exposure scenarios for each worker group. To these exposure scenarios, we applied a previously developed semi-empirical mathematical model that predicts area as well as personal breathing zone respirable dust concentrations. An empirical factor was used to estimate chrysotile fiber concentrations from respirable dust concentrations. On a task basis, we found mean 8-h TWA concentrations of respirable dust and chrysotile fibers are numerically highest for specialists, followed by generalists, DIYers, and bystander tradespersons; these concentrations are estimated to be in excess of the respective current but not historical Threshold Limit Values. Due to differences in frequency of activities, annual cumulative exposures are highest for specialists, followed by generalists, bystander tradespersons, and DIYers. Cumulative exposure estimates for chrysotile fibers from drywall finishing are expected to result in few, if any, mesothelioma or excess lung cancer deaths according to recently published risk assessments. Given the dustiness of drywall finishing, we recommend diligence in the use of readily available source controls.}, } @article {pmid25421663, year = {2015}, author = {Zhang, X and Tang, N and Rishi, AK and Pass, HI and Wali, A}, title = {Methylation profile landscape in mesothelioma: possible implications in early detection, disease progression, and therapeutic options.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {1238}, number = {}, pages = {235-247}, doi = {10.1007/978-1-4939-1804-1_12}, pmid = {25421663}, issn = {1940-6029}, mesh = {Biomarkers, Tumor/genetics ; *DNA Methylation ; *Disease Progression ; Early Detection of Cancer/*methods ; Epigenesis, Genetic ; Humans ; Mesothelioma/*diagnosis/genetics/*therapy ; }, abstract = {Malignant Pleural Mesothelioma (MPM) is an aggressive malignancy of the pleura associated with asbestos exposure. Incidence of MPM is expected to increase over the course of next decade in both Europe and the developing countries. Although significant progress has been made in terms of etiology and pathogenesis of this disease, currently available therapeutic options have not significantly improved the survival outcome of patients on standard chemotherapeutic regimens. Integrity of the cellular DNA is often altered in many cancers. Understanding of the molecular mechanisms that regulate cellular DNA alterations to facilitate cancer initiation and development has potential to allow better design of cancer cell inhibitory strategies. In this context, there is a need to explore the gamut of "omics" strategies to provide a comprehensive epigenetics profile for MPM. This chapter discusses the functional genomics and epigenetic patterns observed by various investigators studying MPM patient populations on global fronts, and attempts to present a holistic approach in combating this insidious disease. Here we provide investigators in this field with novel insights and methodologies used in other types of cancers that might have profound impact in the early detection, prognosis and potential therapeutic strategies for MPM.}, } @article {pmid25410850, year = {2014}, author = {Assis, Ld and Isoldi, MC}, title = {The development of MM is strongly correlated with exposure to asbestos and erionite, as well as to simian virus 40”.}, journal = {Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia}, volume = {40}, number = {5}, pages = {586-587}, pmid = {25410850}, issn = {1806-3756}, mesh = {Humans ; Lung Neoplasms/*genetics/*metabolism ; Mesothelioma/*genetics/*metabolism ; }, } @article {pmid25410479, year = {2014}, author = {Rittinghausen, S and Hackbarth, A and Creutzenberg, O and Ernst, H and Heinrich, U and Leonhardt, A and Schaudien, D}, title = {The carcinogenic effect of various multi-walled carbon nanotubes (MWCNTs) after intraperitoneal injection in rats.}, journal = {Particle and fibre toxicology}, volume = {11}, number = {}, pages = {59}, pmid = {25410479}, issn = {1743-8977}, mesh = {Abdominal Neoplasms/*chemically induced/metabolism/pathology ; Animals ; Carcinogenicity Tests ; Carcinogens/administration & dosage/chemistry/*toxicity ; Dose-Response Relationship, Drug ; Immunohistochemistry ; Injections, Intraperitoneal ; Male ; Mesothelioma/*chemically induced/metabolism/pathology ; Microscopy, Electron, Scanning ; Nanotubes, Carbon/chemistry/*toxicity/ultrastructure ; Neoplasm Invasiveness ; Neoplasm Proteins/metabolism ; Particle Size ; Rats, Wistar ; Serous Membrane ; Survival Analysis ; }, abstract = {BACKGROUND: Biological effects of tailor-made multi-walled carbon nanotubes (MWCNTs) without functionalization were investigated in vivo in a two-year carcinogenicity study. In the past, intraperitoneal carcinogenicity studies in rats using biopersistent granular dusts had always been negative, whereas a number of such studies with different asbestos fibers had shown tumor induction. The aim of this study was to identify possible carcinogenic effects of MWCNTs. We compared induced tumors with asbestos-induced mesotheliomas and evaluated their relevance for humans by immunohistochemical methods.

METHODS: A total of 500 male Wistar rats (50 per group) were treated once by intraperitoneal injection with 10⁹ or 5 × 10⁹ WHO carbon nanotubes of one of four different MWCNTs suspended in artificial lung medium, which was also used as negative control. Amosite asbestos (10⁸ WHO fibers) served as positive control. Morbid rats were sacrificed and necropsy comprising all organs was performed. Histopathological classification of tumors and, additionally, immunohistochemistry were conducted for podoplanin, pan-cytokeratin, and vimentin to compare induced tumors with malignant mesotheliomas occurring in humans.

RESULTS: Treatments induced tumors in all dose groups, but incidences and times to tumor differed between groups. Most tumors were histologically and immunohistochemically classified as malignant mesotheliomas, revealing a predominantly superficial spread on the serosal surface of the abdominal cavity. Furthermore, most tumors showed invasion of peritoneal organs, especially the diaphragm. All tested MWCNT types caused mesotheliomas. We observed highest frequencies and earliest appearances after treatment with the rather straight MWCNT types A and B. In the MWCNT C groups, first appearances of morbid mesothelioma-bearing rats were only slightly later. Later during the two-year study, we found mesotheliomas also in rats treated with MWCNT D - the most curved type of nanotubes. Malignant mesotheliomas induced by intraperitoneal injection of different MWCNTs and of asbestos were histopathologically and immunohistochemically similar, also compared with mesotheliomas in man, suggesting similar pathogenesis.

CONCLUSION: We showed a carcinogenic effect for all tested MWCNTs. Besides aspect ratio, curvature seems to be an important parameter influencing the carcinogenicity of MWCNTs.}, } @article {pmid25408576, year = {2014}, author = {Lee, YJ and Hwang, IS and Lee, YJ and Lee, CH and Kim, SH and Nam, HS and Choi, YJ and Lee, SH}, title = {Knockdown of Bcl-xL enhances growth-inhibiting and apoptosis-inducing effects of resveratrol and clofarabine in malignant mesothelioma H-2452 cells.}, journal = {Journal of Korean medical science}, volume = {29}, number = {11}, pages = {1464-1472}, pmid = {25408576}, issn = {1598-6357}, mesh = {Adenine Nucleotides/*pharmacology ; Antimetabolites, Antineoplastic/*pharmacology ; Apoptosis/*drug effects ; Arabinonucleosides/*pharmacology ; Caspase 3/metabolism ; Caspase 7/metabolism ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Clofarabine ; G2 Phase Cell Cycle Checkpoints/drug effects ; Gene Knockdown Techniques ; Humans ; Leupeptins/pharmacology ; Lung Neoplasms/metabolism/pathology ; M Phase Cell Cycle Checkpoints/drug effects ; Mesothelioma/metabolism/pathology ; Mesothelioma, Malignant ; Myeloid Cell Leukemia Sequence 1 Protein/antagonists & inhibitors/genetics/metabolism ; RNA Interference ; RNA, Messenger/metabolism ; RNA, Small Interfering/metabolism ; Resveratrol ; Stilbenes/*pharmacology ; bcl-X Protein/antagonists & inhibitors/*genetics/*metabolism ; }, abstract = {Mcl-1 and Bcl-xL, key anti-apoptotic proteins of the Bcl-2 family, have attracted attention as important molecules in the cell survival and drug resistance. In this study, we investigated whether inhibition of Bcl-xL influences cell growth and apoptosis against simultaneous treatment of resveratrol and clofarabine in the human malignant mesothelioma H-2452 cells. Resveratrol and clofarabine decreased Mcl-1 protein levels but had little effect on Bcl-xL levels. In the presence of two compounds, any detectable change in the Mcl-1 mRNA levels was not observed in RT-PCR analysis, whereas pretreatment with the proteasome inhibitor MG132 led to its accumulation to levels far above basal levels. The knockdown of Bcl-xL inhibited cell proliferation with cell accumulation at G2/M phase and the appearance of sub-G0/G1 peak in DNA flow cytometric assay. The suppression of cell growth was accompanied by an increase in the caspase-3/7 activity with the resultant cleavages of procaspase-3 and its substrate poly (ADP-ribose) polymerase, and increased percentage of apoptotic propensities in annexin V binding assay. Collectively, our data represent that the efficacy of resveratrol and clofarabine for apoptosis induction was substantially enhanced by Bcl-xL-lowering strategy in which the simultaneous targeting of Mcl-1 and Bcl-xL could be a more effective strategy for treating malignant mesothelioma.}, } @article {pmid25388904, year = {2015}, author = {Zanker, F and Zellner, M and Busche, J and Woziwodski, J}, title = {[Paratesticular mesothelioma].}, journal = {Der Urologe. Ausg. A}, volume = {54}, number = {3}, pages = {394-396}, pmid = {25388904}, issn = {1433-0563}, mesh = {Diagnosis, Differential ; Humans ; Male ; Mesothelioma/*diagnosis/*therapy ; Occupational Diseases/*diagnosis/*therapy ; Testicular Neoplasms/*diagnosis/*therapy ; Treatment Outcome ; }, abstract = {Paratesticular mesothelioma is a very rare entity of this aggressive malignancy. In 30-40 % of all cases an exposition to asbestos exists in the anamnesis. We report on a typical case of paratesticular mesothelioma in a roof slater and tiler who had had occupational contact with asbestos-containing materials over decades. The recommended diagnostics and therapy are discussed and the importance of the identification as an occupational disease is emphasized.}, } @article {pmid25386835, year = {2015}, author = {Germine, M and Puffer, JH}, title = {Analytical Transmission Electron Microscopy of Amphibole Fibers From the Lungs of Quebec Miners.}, journal = {Archives of environmental & occupational health}, volume = {70}, number = {6}, pages = {323-331}, doi = {10.1080/19338244.2014.918928}, pmid = {25386835}, issn = {2154-4700}, mesh = {Air Pollutants, Occupational/*analysis/chemistry ; Asbestos, Amphibole/*analysis/chemistry ; Cohort Studies ; Lung Neoplasms/chemically induced/pathology/*ultrastructure ; Mesothelioma/chemically induced/pathology/*ultrastructure ; Microscopy, Electron, Transmission ; *Miners ; Occupational Diseases/*pathology ; Quebec ; }, abstract = {The objective of this study is to describe the morphology, molecular structure, and chemistry of amphibole fibers from lung samples from workers in the chrysotile mines at Asbestos and Thetford Mines, Quebec. A fibrous tremolite-actinolite contaminant in an asbestos ore sample from the deposit at Asbestos was used for comparison. Lattice imaging was performed using high-resolution transmission electron microscopy (HRTEM). Silica-rich amorphous coatings (SIRA) that may be related to carcinogenesis are noted on all of the HRTEM photographs of fibers retained in lung, but not on fiber surfaces of the bulk comparison sample. Fibers found in lung samples and in a bulk comparison sample are produced primarily by splitting of thicker crystals and, as such, might not be considered asbestos fibers on the basis of certain mineralogical criteria. Implications of SIRA coatings with respect to carcinogenesis are worthy of further study.}, } @article {pmid25382807, year = {2015}, author = {Kao, SC and van Zandwijk, N and Clarke, S and Vardy, J and Lumba, S and Tognela, A and Ng, W}, title = {Estimation of an optimal chemotherapy utilization rate for malignant pleural mesothelioma: an evidence-based benchmark for cancer care.}, journal = {Asia-Pacific journal of clinical oncology}, volume = {11}, number = {1}, pages = {85-92}, doi = {10.1111/ajco.12306}, pmid = {25382807}, issn = {1743-7563}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*standards/*therapeutic use ; *Benchmarking ; *Evidence-Based Medicine ; Humans ; Lung Neoplasms/*drug therapy/pathology ; Medical Oncology/*standards ; Mesothelioma/*drug therapy/pathology ; Mesothelioma, Malignant ; Models, Statistical ; Neoplasm Staging ; Pleural Neoplasms/*drug therapy/pathology ; Practice Guidelines as Topic/*standards ; Prognosis ; Quality of Health Care ; Quality of Life ; }, abstract = {AIMS: Chemotherapy with cisplatin and pemetrexed has been shown to provide a survival benefit and improvement in quality of life in patients with malignant pleural mesothelioma (MPM). The reported chemotherapy utilization rates range from 18% to 61%. This study aimed to estimate the proportion of MPM patients that should receive chemotherapy based on best available evidence.

METHODS: An optimal chemotherapy utilization model for MPM was constructed using indications for chemotherapy identified from evidence-based MPM treatment guidelines. Epidemiological data on the proportion of patients and their tumor-related attributes were combined with the chemotherapy indications to estimate the optimal chemotherapy utilization rate using decision analysis software (TreeAge Pro 2007). Sensitivity analyses were performed to assess the impact of major variations in the epidemiological data on the optimal chemotherapy utilization rate. The optimal rate was compared with the actual rate reported in the literature.

RESULTS: Chemotherapy is recommended at least once during the disease trajectory in 65% of MPM patients. Sensitivity analyses indicate an optimal utilization rate ranging from 50% to 65%. This optimal rate is relatively comparable to the rates mentioned in contemporary reports from Canada (61% between 2003 and 2005) and Australia (54% between 2007 and 2009) and high when compared with data from the Netherlands (36% during 2005-2006).

CONCLUSION: An evidence-based model provided an optimal chemotherapy utilization rate of 65% for patients with MPM. Chemotherapy for MPM may be underutilized and barriers are likely multifactorial.}, } @article {pmid25378740, year = {2014}, author = {Kameda, T and Takahashi, K and Kim, R and Jiang, Y and Movahed, M and Park, EK and Rantanen, J}, title = {Asbestos: use, bans and disease burden in Europe.}, journal = {Bulletin of the World Health Organization}, volume = {92}, number = {11}, pages = {790-797}, pmid = {25378740}, issn = {1564-0604}, support = {001/WHO_/World Health Organization/International ; }, mesh = {Asbestos/*toxicity ; Asbestosis/*mortality ; Databases, Factual ; Europe/epidemiology ; Female ; Humans ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; World Health Organization ; }, abstract = {OBJECTIVE: To analyse national data on asbestos use and related diseases in the European Region of the World Health Organization (WHO).

METHODS: For each of the 53 countries, per capita asbestos use (kg/capita/year) and age-adjusted mortality rates (deaths/million persons/year) due to mesothelioma and asbestosis were calculated using the databases of the United States Geological Survey and WHO, respectively. Countries were further categorized by ban status: early-ban (ban adopted by 2000, n = 17), late-ban (ban adopted 2001-2013, n = 17), and no-ban (n = 19).

FINDINGS: Between 1920-2012, the highest per capita asbestos use was found in the no-ban group. After 2000, early-ban and late-ban groups reduced their asbestos use levels to less than or equal to 0.1 kg/capita/year, respectively, while the no-ban group maintained a very high use at 2.2 kg/capita/year. Between 1994 and 2010, the European Region registered 106,180 deaths from mesothelioma and asbestosis, accounting for 60% of such deaths worldwide. In the early-ban and late-ban groups, 16/17 and 15/17 countries, respectively, reported mesothelioma data to WHO, while only 6/19 countries in the no-ban group reported such data. The age-adjusted mortality rates for mesothelioma for the early-ban, late-ban and no-ban groups were 9.4, 3.7 and 3.2 deaths/million persons/year, respectively. Asbestosis rates for the groups were 0.8, 0.9 and 1.5 deaths/million persons/year, respectively.

CONCLUSION: Within the European Region, the early-ban countries reported most of the current asbestos-related deaths. However, this might shift to the no-ban countries, since the disease burden will likely increase in these countries due the heavy use of asbestos.}, } @article {pmid25374934, year = {2014}, author = {Hajok, I and Marchwińska, E and Dziubanek, G and Kuraszewska, B and Piekut, A}, title = {Environmentally related diseases and the possibility of valuation of their social costs.}, journal = {TheScientificWorldJournal}, volume = {2014}, number = {}, pages = {284072}, pmid = {25374934}, issn = {1537-744X}, mesh = {Asbestos/*adverse effects ; Humans ; Incidence ; Lung Neoplasms/*epidemiology/etiology ; Mesothelioma/*epidemiology/etiology ; Occupational Diseases/*epidemiology/etiology ; *Occupational Exposure ; Poland/epidemiology ; Risk Factors ; }, abstract = {The risks of the morbidity of the asbestos-related lung cancer was estimated in the general population of Poles as the result of increased exposure to asbestos fibers during the removal of asbestos-cement products and the possibility of the valuation of the social costs related to this risk. The prediction of the new incidences was made using linear regression model. The forecast shows that to the end of 2030 about 3,500 new cases of lung cancer can be expected as a result of occupational exposure to asbestos in the past which makes together with paraoccupational exposure about 14.000 new cases. The forecast shows the increasing number of asbestos-related lung cancer in Poland and indicates the priority areas where preventive action should be implemented.}, } @article {pmid25358858, year = {2014}, author = {Maeda, M and Chen, Y and Hayashi, H and Kumagai-Takei, N and Matsuzaki, H and Lee, S and Nishimura, Y and Otsuki, T}, title = {Chronic exposure to asbestos enhances TGF-β1 production in the human adult T cell leukemia virus-immortalized T cell line MT-2.}, journal = {International journal of oncology}, volume = {45}, number = {6}, pages = {2522-2532}, doi = {10.3892/ijo.2014.2682}, pmid = {25358858}, issn = {1791-2423}, mesh = {Adult ; Annexin A5/metabolism ; Apoptosis/genetics ; Asbestos/*toxicity ; Cell Line, Tumor ; Cell Proliferation/*drug effects ; Gene Knockdown Techniques ; Humans ; Immune System/drug effects/pathology ; Leukemia-Lymphoma, Adult T-Cell/chemically induced/*genetics/pathology ; Transforming Growth Factor beta1/biosynthesis/*genetics ; p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism ; }, abstract = {Asbestos exposure causes various tumors such as lung cancer and malignant mesothelioma. To elucidate the immunological alteration in asbestos-related tumors, an asbestos-induced apoptosis-resistant subline (MT-2Rst) was established from a human adult T cell leukemia virus-immortalized T cell line (MT-2Org) by long-term exposure to asbestos chrysotile-B (CB). In this study, transforming growth factor-β1 (TGF-β1) knockdown using lentiviral vector-mediated RNA interference showed that MT-2Rst cells secreted increased levels of TGF-β1, and acquired resistance to TGF-β1-mediated growth inhibition. We showed that exposure of MT-2Org cells to CB activated the mitogen-activated protein kinases (MAPKs), ERK1/2, p38 and JNK1. Furthermore, TGF-β1-knockdown cells and treatment with MAPK inhibitors revealed that MT-2Rst cells secreted a high level of TGF-β1 mainly through phosphorylation of p38. However, an Annexin V assay indicated that TGF-β1 resistance in MT-2Rst cells was not directly involved in the acquisition of resistance to apoptosis that is triggered by CB exposure. The overall results demonstrate that long-term exposure of MT-2Org cells to CB induces a regulatory T cell-like phenotype, suggesting that chronic exposure to asbestos leads to a state of immune suppression.}, } @article {pmid25335827, year = {2015}, author = {García-Gómez, M and Menéndez-Navarro, A and López, RC}, title = {Asbestos-related occupational cancers compensated under the Spanish National Insurance System, 1978-2011.}, journal = {International journal of occupational and environmental health}, volume = {21}, number = {1}, pages = {31-39}, pmid = {25335827}, issn = {2049-3967}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Bronchial Neoplasms/chemically induced/*epidemiology/mortality ; Europe/epidemiology ; European Union/statistics & numerical data ; Female ; Humans ; Incidence ; Lung Neoplasms/chemically induced/*epidemiology/mortality ; Male ; Mesothelioma/chemically induced/*epidemiology/mortality ; Middle Aged ; Occupational Diseases/chemically induced/*epidemiology ; *Occupational Exposure/statistics & numerical data ; Spain/epidemiology ; }, abstract = {BACKGROUND: In 1978, asbestos-related occupational cancers were added to the Spanish list of occupational diseases. However, there are no full accounts of compensated cases since their inclusion.

OBJECTIVE: To analyze the cases of asbestos-related cancer recognized as occupational in Spain between 1978 and 2011.

METHODS: Cases were obtained from the Spanish Employment Ministry. Specific incidence rates by year, economic activity, and occupation were obtained. We compared mortality rates of mesothelioma and bronchus and lung cancer mortality in Spain and the European Union.

RESULTS: Between 1978 and 2011, 164 asbestos-related occupational cancers were recognized in Spain, with a mean annual rate of 0·08 per 10(5) employees (0·13 in males, 0·002 in females). Under-recognition rates were an estimated 93·6% (males) and 99·7% (females) for pleural mesothelioma and 98·8% (males) and 100% (females) for bronchus and lung cancer. In Europe for the year 2000, asbestos-related occupational cancer rates ranged from 0·04 per 10(5) employees in Spain to 7·32 per 10(5) employees in Norway.

CONCLUSIONS: These findings provide evidence of gross under-recognition of asbestos-related occupational cancers in Spain. Future work should investigate cases treated in the National Healthcare System to better establish the impact of asbestos on health in Spain.}, } @article {pmid25331029, year = {2015}, author = {Cao, S and Jin, S and Cao, J and Shen, J and Hu, J and Che, D and Pan, B and Zhang, J and He, X and Ding, D and Gu, F and Yu, Y}, title = {Advances in malignant peritoneal mesothelioma.}, journal = {International journal of colorectal disease}, volume = {30}, number = {1}, pages = {1-10}, pmid = {25331029}, issn = {1432-1262}, mesh = {Diagnosis, Differential ; Female ; Humans ; *Lung Neoplasms/diagnosis/epidemiology/therapy ; Male ; *Mesothelioma/diagnosis/epidemiology/therapy ; Mesothelioma, Malignant ; *Peritoneal Neoplasms/diagnosis/epidemiology/therapy ; Prognosis ; }, abstract = {BACKGROUND: Malignant mesothelioma is a rare, insidious, and aggressive tumor arising from the mesothelial surface of pleural and peritoneal cavities, the pericardium, or the tunica vaginalis, with an increasing incidence worldwide, high misdiagnosis rate, and overall negative prognosis. A total of 20% of all cases is peritoneum in origin.

METHODS: The present study is a review of literatures focusing on the advances in epidemiology, clinical presentations, radiological features, diagnosis, misdiagnosis, management, and prognostic factors of malignant peritoneal mesothelioma (MPM) occurred in the past decades.

RESULTS: Asbestos, SV40, and radiation exposures have been demonstrated to be correlated with the pathogenesis of MPM. The main presentations are abdominal distension and pain. Computed tomography (CT), magnetic resonance imaging (MRI), and positron-emission tomography (PET) play an important role in the preoperative imaging and staging. Definitive diagnosis is made on the basis of immunohistochemistry. Prognostic factors have been identified and verified. Negative indicators include advanced age, male gender, poor performance status, non-epithelial histology, and absence of surgery. The management of MPM has evolved from single chemotherapy to multimodality treatment of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), chemotherapy, radiotherapy, and immunotherapy. Promising results have been achieved after a combined treatment of CRS and HIPEC, with an elevated median survival time of 29.5-92 months and a 5-year survival rate of 39-63%.

CONCLUSIONS: CRS and HIPEC represent the standard treatment strategy for selected patients with MPM, and patients with unresectable tumors can benefit from the combined treatment of chemotherapy, radiotherapy, and immunotherapy.}, } @article {pmid25325160, year = {2015}, author = {Palomäki, J and Sund, J and Vippola, M and Kinaret, P and Greco, D and Savolainen, K and Puustinen, A and Alenius, H}, title = {A secretomics analysis reveals major differences in the macrophage responses towards different types of carbon nanotubes.}, journal = {Nanotoxicology}, volume = {9}, number = {6}, pages = {719-728}, doi = {10.3109/17435390.2014.969346}, pmid = {25325160}, issn = {1743-5404}, mesh = {Apoptosis/drug effects ; Asbestos, Crocidolite/chemistry/toxicity ; Blotting, Western ; Cells, Cultured ; Cluster Analysis ; Culture Media, Serum-Free ; Electrophoresis, Gel, Two-Dimensional ; Enzyme-Linked Immunosorbent Assay ; Humans ; Macrophages/*drug effects/*metabolism/pathology ; Nanotubes, Carbon/chemistry/*toxicity ; Proteins/*metabolism ; Surface Properties ; }, abstract = {Certain types of carbon nanotubes (CNT) can evoke inflammation, fibrosis and mesothelioma in vivo, raising concerns about their potential health effects. It has been recently postulated that NLRP3 inflammasome activation is important in the CNT-induced toxicity. However, more comprehensive studies of the protein secretion induced by CNT can provide new information about their possible pathogenic mechanisms. Here, we studied protein secretion from human macrophages with a proteomic approach in an unbiased way. Human monocyte-derived macrophages (MDM) were exposed to tangled or rigid, long multi-walled CNT (MWCNT) or crocidolite asbestos for 6 h. The growth media was concentrated and secreted proteins were analyzed using 2D-DIGE and DeCyder software. Subsequently, significantly up- or down-regulated protein spots were in-gel digested and identified with an LC-MS/MS approach. Bioinformatics analysis was performed to reveal the different patterns of protein secretion induced by these materials. The results show that both long rigid MWCNT and asbestos elicited ample and highly similar protein secretion. In contrast, exposure to long tangled MWCNT induced weaker protein secretion with a more distinct profile. Secretion of lysosomal proteins followed the exposure to all materials, suggesting lysosomal damage. However, only long rigid MWCNT was associated with apoptosis. This analysis suggests that the CNT toxicity in human MDM is mediated via vigorous secretion of inflammation-related proteins and apoptosis. This study provides new insights into the mechanisms of toxicity of high aspect ratio nanomaterials and indicates that not all types of CNT are as hazardous as asbestos fibers.}, } @article {pmid25324587, year = {2014}, author = {Okada, F}, title = {Inflammation-related carcinogenesis: current findings in epidemiological trends, causes and mechanisms.}, journal = {Yonago acta medica}, volume = {57}, number = {2}, pages = {65-72}, pmid = {25324587}, issn = {0513-5710}, abstract = {Inflammation is a definite cancer-causing factor as revealed by cumulative basic, clinical and epidemiological studies. It is mostly induced by infectious agents. For instance, infection with papillomaviruses associates with anogenital cancers, especially cervical cancers; Helicobacter pylori infection of the stomach tends to increase the risk of stomach cancer; chronic hepatitis B & C viruses and fluke infections of the liver increase liver cancers; autoimmune diseases, e.g., inflammatory bowel diseases, associate with development of colorectal cancer, and aerial irritants (foreign bodies) such as asbestos or fine particulate matter (PM2.5) in outdoor air increase malignant pleural mesotheliomas or lung cancers. These are typical examples of inflammation-related carcinogenesis. It is apparent that the pathogens to induce inflammatory reactions in specific organs are not related to each other. However, the underlying pathogenesis in common is to induce and/or sustain inflammation. In this article, I would like to review the up-to-date findings of epidemiological trends, causes and mechanisms of inflammation-related carcinogenesis.}, } @article {pmid25316312, year = {2015}, author = {McDonnell, AM and Lesterhuis, WJ and Khong, A and Nowak, AK and Lake, RA and Currie, AJ and Robinson, BW}, title = {Tumor-infiltrating dendritic cells exhibit defective cross-presentation of tumor antigens, but is reversed by chemotherapy.}, journal = {European journal of immunology}, volume = {45}, number = {1}, pages = {49-59}, doi = {10.1002/eji.201444722}, pmid = {25316312}, issn = {1521-4141}, mesh = {Animals ; Antigen Presentation/genetics ; Antigens, Neoplasm/genetics/*immunology ; Antimetabolites, Antineoplastic/*pharmacology ; CD11b Antigen/genetics/immunology ; CD4-Positive T-Lymphocytes/immunology/pathology ; Cell Movement ; Coculture Techniques ; Cross-Priming/genetics ; Dendritic Cells/*immunology/pathology ; Deoxycytidine/*analogs & derivatives/pharmacology ; Gene Expression ; Hemagglutinins/genetics/immunology ; Lymph Nodes/immunology/pathology ; Mesothelioma/*drug therapy/genetics/immunology/pathology ; Mice ; Mice, Transgenic ; Neoplasm Transplantation ; Skin Neoplasms/*drug therapy/genetics/immunology/pathology ; T-Lymphocytes, Cytotoxic/immunology/pathology ; Tumor Microenvironment ; Gemcitabine ; }, abstract = {Cross-presentation defines the unique capacity of an APC to present exogenous Ag via MHC class I molecules to CD8(+) T cells. DCs are specialized cross-presenting cells and as such have a critical role in antitumor immunity. DCs are routinely found within the tumor microenvironment, but their capacity for endogenous or therapeutically enhanced cross-presentation is not well characterized. In this study, we examined the tumor and lymph node DC cross-presentation of a nominal marker tumor Ag, HA, expressed by the murine mesothelioma tumor AB1-HA. We found that tumors were infiltrated by predominantly CD11b(+) DCs with a semimature phenotype that could not cross-present tumor Ag, and therefore, were unable to induce tumor-specific T-cell activation or proliferation. Although tumor-infiltrating DCs were able to take up, process, and cross-present exogenous cell-bound and soluble Ags, this was significantly impaired relative to lymph node DCs. Importantly, however, systemic chemotherapy using gemcitabine reversed the defect in Ag cross-presentation of tumor DCs. These data demonstrate that DC cross-presentation within the tumor microenvironment is defective, but can be reversed by chemotherapy. These results have important implications for anticancer therapy, particularly regarding the use of immunotherapy in conjunction with cytotoxic chemotherapy.}, } @article {pmid25310424, year = {2014}, author = {Nickell, LT and Lichtenberger, JP and Khorashadi, L and Abbott, GF and Carter, BW}, title = {Multimodality imaging for characterization, classification, and staging of malignant pleural mesothelioma.}, journal = {Radiographics : a review publication of the Radiological Society of North America, Inc}, volume = {34}, number = {6}, pages = {1692-1706}, doi = {10.1148/rg.346130089}, pmid = {25310424}, issn = {1527-1323}, mesh = {Contrast Media ; Humans ; Lung Neoplasms/*diagnosis/pathology/therapy ; Lymphatic Metastasis ; Mesothelioma/*diagnosis/pathology/therapy ; Mesothelioma, Malignant ; *Multimodal Imaging ; Neoplasm Staging ; Pleural Neoplasms/*diagnosis/pathology/therapy ; Risk Factors ; }, abstract = {Malignant pleural mesothelioma (MPM) is the most common primary malignancy of the pleura and is associated with asbestos exposure in approximately 80% of patients. The patient prognosis is poor, with a median survival of 9-17 months after diagnosis. However, improved survival and decreased morbidity and mortality have been demonstrated when the diagnosis is made in the early stages of disease and specific treatment strategies are implemented. A staging system that focuses on the extent of primary tumor (T), lymph node involvement (N), and metastatic disease (M) has been devised by the International Mesothelioma Interest Group and emphasizes factors related to overall survival. Radiologists should recognize the manifestations of MPM across multiple imaging modalities, translate these findings into the updated staging system, and understand the effects of appropriate staging on treatment and survival. Computed tomography (CT) remains the primary imaging modality used to evaluate MPM and efficiently demonstrates the extent of primary tumor, intrathoracic lymphadenopathy, and extrathoracic spread. However, additional imaging modalities, such as magnetic resonance (MR) imaging of the thorax and positron emission tomography (PET)/CT with fluorodeoxyglucose, have emerged in recent years and are complementary to CT for disease staging and evaluation of patients with MPM. Thoracic MR imaging is particularly useful for identifying invasion of the chest wall, mediastinum, and diaphragm, and PET/CT can accurately demonstrate intrathoracic and extrathoracic lymphadenopathy and metastatic disease.}, } @article {pmid25299403, year = {2015}, author = {Wolff, H and Vehmas, T and Oksa, P and Rantanen, J and Vainio, H}, title = {Asbestos, asbestosis, and cancer, the Helsinki criteria for diagnosis and attribution 2014: recommendations.}, journal = {Scandinavian journal of work, environment & health}, volume = {41}, number = {1}, pages = {5-15}, doi = {10.5271/sjweh.3462}, pmid = {25299403}, issn = {1795-990X}, mesh = {Asbestos/*adverse effects ; Asbestosis/*diagnosis/etiology ; Biomarkers/blood ; Female ; Finland ; Guidelines as Topic/standards ; Humans ; Male ; Mesothelioma/diagnosis/etiology ; Neoplasms/*diagnosis/etiology ; Occupational Exposure ; Pleural Diseases/diagnosis/etiology ; Pulmonary Disease, Chronic Obstructive/diagnosis/etiology ; Retroperitoneal Fibrosis/diagnosis/etiology ; }, } @article {pmid25297446, year = {2015}, author = {Jin, S and Cao, S and Cao, J and Shen, J and Hu, J and Che, D and Zhang, J and Yu, Y}, title = {Predictive factors analysis for malignant peritoneal mesothelioma.}, journal = {Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract}, volume = {19}, number = {2}, pages = {319-326}, pmid = {25297446}, issn = {1873-4626}, mesh = {Abdominal Pain/etiology ; Adult ; Age Factors ; Aged ; Antineoplastic Agents/*therapeutic use ; Combined Modality Therapy ; *Cytoreduction Surgical Procedures ; Female ; Humans ; Male ; Mesothelioma/complications/*therapy ; Middle Aged ; Peritoneal Neoplasms/complications/*therapy ; Prognosis ; Retrospective Studies ; Survival Rate ; }, abstract = {BACKGROUND: Malignant peritoneal mesothelioma (MPM) is an uncommon disease with a dismal prognosis and unclear natural history. The present study aims to assess potential prognostic factors and management of MPM.

METHODS: Clinical records of 39 patients with MPM between December 2003 and April 2014 were retrospectively reviewed. Overall survival was identified with Kaplan-Meier curves and Cox regression analysis.

RESULTS: Mean age of 39 patients was 55.0 years; asbestos exposure was recorded in two patients. Main presentations were abdominal distension, abdominal pain, and weight loss. Thrombocytosis, low serum albumin level, and anemia were principal laboratory abnormalities. Ascites, peritoneal cavity mass, and peritoneum thickening were the main signs on CT scans. Cytoreductive surgery (CRS) plus adjuvant therapies were performed in 22 patients, single chemotherapy in 13, and best supportive care in 4. Median survival time was 10.0 months after pathological diagnosis, with a 6-, 12-, 18-, and 24-month survival rate of 84.4, 31.6, 18.5, and 15.8 %, respectively. Significant prognostic factors were age, performance status (PS), abdominal pain, serum albumin level, thrombocytosis, and treatment strategy on univariate analysis, while only age, abdominal pain, and treatment strategy hold statistical significance on multivariate analysis.

CONCLUSIONS: Age ≤65 years, abdominal pain, and CRS plus adjuvant therapy are independent positive prognostic factors of MPM.}, } @article {pmid25296690, year = {2014}, author = {Nemo, A and Silvestri, S}, title = {Mesothelioma in a wine cellar man: detailed description of working procedures and past asbestos exposure estimation.}, journal = {The Annals of occupational hygiene}, volume = {58}, number = {9}, pages = {1168-1174}, doi = {10.1093/annhyg/meu062}, pmid = {25296690}, issn = {1475-3162}, mesh = {Air Pollutants, Occupational/analysis/*toxicity ; Asbestos/*toxicity ; Carcinogens/*toxicity ; Humans ; Male ; Mesothelioma/*etiology ; Occupational Exposure/*adverse effects/analysis ; Pleural Neoplasms/*etiology ; Regression Analysis ; Risk Assessment ; *Wine ; }, abstract = {A pleural mesothelioma arose in an employee of a wine farm whose work history shows an unusual occupational exposure to asbestos. The information, gathered directly from the case and from a work colleague, clarifies some aspects of the use of asbestos in the process of winemaking which has not been previously reported in such details. The man had worked as a winemaker from 1960 to 1988 in a farm, which in those years produced around 2500 hectoliters of wine per year, mostly white. The wine was filtered to remove impurities; the filter was created by dispersing in the wine asbestos fibers followed by diatomite while the wine was circulating several times and clogging a prefilter made of a dense stainless steel net. Chrysotile asbestos was the sole asbestos mineralogical variety used in these filters and exposure could occur during the phase of mixing dry fibers in the wine and during the filter replacement. A daily and annual time weighted average level of exposure and cumulative dose have been estimated in the absence of airborne asbestos fiber monitoring performed in that workplace. Since 1993, the Italian National Mesothelioma Register, an epidemiological surveillance system, has recorded eight cases with at least one work period spent as winemaker. Four of them never used asbestos filters and presented exposures during other work periods, the other four used asbestos filters but had also other exposures in other industrial divisions. For the information hitherto available, this is the first mesothelioma case with exclusive exposure in the job of winemaking.}, } @article {pmid25285978, year = {2014}, author = {Banks, DE}, title = {Clinical aspects of asbestos-related diseases--what are the unresolved topics?.}, journal = {Journal of occupational and environmental medicine}, volume = {56 Suppl 10}, number = {}, pages = {S8-S12}, doi = {10.1097/JOM.0000000000000242}, pmid = {25285978}, issn = {1536-5948}, mesh = {Age Factors ; Aged ; Asbestosis/*diagnosis/mortality/*prevention & control ; Cross-Cultural Comparison ; Cross-Sectional Studies ; Humans ; Life Expectancy ; Male ; Maximum Allowable Concentration ; Mesothelioma/*diagnosis/mortality/*prevention & control ; Middle Aged ; Occupational Exposure/*adverse effects ; Risk Factors ; Survival Analysis ; United States ; }, abstract = {OBJECTIVE: Despite awareness of the health risks associated with asbestos fiber inhalation and the decline in U.S. utilization (about 0.1% of the yearly peak amount), illnesses associated with exposure persist. Those with disease typically describe excessive exposures in the remote past, yet excessive exposures can occur today, most likely related to careless asbestos abatement procedures. The intent is to address unanswered questions associated with asbestos exposure.

METHODS: The author summarizes clinical information addressing the case definition of asbestosis, the world-wide rate of mesothelioma, and clinical follow-up for those with exposure.

RESULTS: The author describes information relevant to issues which remain unresolved.

CONCLUSION: Perhaps somewhat surprisingly, even though there have been a great number of manuscripts reporting on the health risks of asbestos exposure, there remain unanswered questions regarding the pathogenesis of this disease.}, } @article {pmid25268063, year = {2015}, author = {Oczypok, EA and Oury, TD}, title = {Electron microscopy remains the gold standard for the diagnosis of epithelial malignant mesothelioma: a case study.}, journal = {Ultrastructural pathology}, volume = {39}, number = {2}, pages = {153-158}, pmid = {25268063}, issn = {1521-0758}, support = {F30 ES024045/ES/NIEHS NIH HHS/United States ; T32 HL094295/HL/NHLBI NIH HHS/United States ; 1F30ES024045/ES/NIEHS NIH HHS/United States ; }, mesh = {Biopsy ; Carcinoma, Renal Cell/diagnosis/*pathology ; Humans ; Lung Neoplasms/diagnosis/*pathology ; Male ; Mesothelioma/diagnosis/*pathology ; Mesothelioma, Malignant ; *Microscopy, Electron ; Middle Aged ; Neoplasms, Glandular and Epithelial/*diagnosis/pathology ; Pleural Neoplasms/diagnosis/*pathology ; }, abstract = {This is a case of idiopathic epithelial malignant mesothelioma in a 47-year-old mechanic. The advent of a large battery of immunochemical markers has provided new tools for the diagnosis of mesothelioma in recent years; however, immunostaining can often be misleading or inconsistent, as demonstrated in this case. This report highlights the lasting utility of electron microscopy in the diagnosis of mesothelioma. Ultrastructural features of epithelial mesothelioma were discernable using electron microscopy even on somewhat poorly preserved chest wall biopsy specimens from paraffin blocks. These images, combined with immunostains and a fiber analysis from the lungs, allowed for a final diagnosis of a non-asbestos-related malignant epithelial mesothelioma in this patient.}, } @article {pmid25264933, year = {2014}, author = {Greim, H and Utell, MJ and Maxim, LD and Niebo, R}, title = {Perspectives on refractory ceramic fiber (RCF) carcinogenicity: comparisons with other fibers.}, journal = {Inhalation toxicology}, volume = {26}, number = {13}, pages = {789-810}, pmid = {25264933}, issn = {1091-7691}, mesh = {Animals ; Carcinogens/*toxicity ; Ceramics/*toxicity ; Humans ; Inhalation Exposure/adverse effects ; Kaolin/*toxicity ; Lung Neoplasms/*chemically induced ; Mineral Fibers/*toxicity ; Rats ; }, abstract = {In 2011, SCOEL classified RCF as a secondary genotoxic carcinogen and supported a practical threshold. Inflammation was considered the predominant manifestation of RCF toxicity. Intrapleural and intraperitoneal implantation induced mesotheliomas and sarcomas in laboratory animals. Chronic nose-only inhalation bioassays indicated that RCF exposure in rats increased the incidence of lung cancer and similar exposures resulted in mesothelioma in hamsters, but these studies may have been compromised by overload. Epidemiological studies in the US and Europe showed an association between exposure and prevalence of respiratory symptoms and pleural plaques, but no interstitial fibrosis, mesotheliomas, or increased numbers of lung tumors were observed. As the latency of asbestos induced mesotheliomas can be up to 50 years, the relationship between RCF exposure and respiratory malignances has not been fully determined. Nonetheless, it is possible to offer useful perspectives. RCF and rock wool have similar airborne fiber dimensions and biopersistence. Therefore, it is likely that these fibers have similar toxicology. Traditional rock wool has been the subject of numerous cohort and case control studies. For rock wool, IARC (2002) concluded that the epidemiological studies did not provide evidence of carcinogenicity. Based on analogies with rock wool (read across), it is reasonable to believe that increases in lung cancer or any mesotheliomas are unlikely to be found in the RCF-exposed cohort. RCF producers have developed a product stewardship program to measure and control fiber concentrations and to further understand the health status of their workers.}, } @article {pmid25262213, year = {2014}, author = {Magouliotis, DE and Tasiopoulou, VS and Molyvdas, PA and Gourgoulianis, KI and Hatzoglou, C and Zarogiannis, SG}, title = {Airways microbiota: Hidden Trojan horses in asbestos exposed individuals?.}, journal = {Medical hypotheses}, volume = {83}, number = {5}, pages = {537-540}, doi = {10.1016/j.mehy.2014.09.006}, pmid = {25262213}, issn = {1532-2777}, mesh = {Asbestos/*toxicity ; Cholesterol/chemistry ; Cytotoxins/chemistry ; Epithelial Cells/drug effects/microbiology ; Humans ; Lung/drug effects/*microbiology ; Lung Neoplasms/*microbiology/*physiopathology ; Mesothelioma/*microbiology/*physiopathology ; Mesothelioma, Malignant ; Microbiota ; Models, Biological ; Pleura/drug effects/microbiology ; Pleural Neoplasms/microbiology/physiopathology ; Prognosis ; Streptococcus intermedius ; Streptococcus mitis ; Streptococcus pneumoniae ; Streptococcus pyogenes ; }, abstract = {Malignant pleura mesothelioma (MPM) is a rare type of cancer with devastating prognosis, which develops in the pleural cavity from transformed mesothelium. MPM has been directly associated with asbestos exposure however there are aspects of the pathophysiology involved in the translocation of asbestos fibers in the pleura that remain unclear. Here, we propose and discuss that certain proteins secreted by airways symbiotic microbiota create membrane pores to the airway epithelial cells, through which asbestos fibers can penetrate the lung parenchyma and reach the sub-pleural areas. We evaluate this hypothesis using data from the published literature regarding the airways microbiota toxins such as cholesterol-dependent cytolysins (CDCs).}, } @article {pmid25260287, year = {2014}, author = {Acton, V}, title = {Preventing pleural mesothelioma in patients with recognizable asbestos-related pleural plaques.}, journal = {The Journal of thoracic and cardiovascular surgery}, volume = {148}, number = {4}, pages = {1763}, doi = {10.1016/j.jtcvs.2014.03.030}, pmid = {25260287}, issn = {1097-685X}, mesh = {Female ; Humans ; Male ; Mesothelioma/*surgery ; Pleural Neoplasms/*surgery ; *Thoracic Surgical Procedures ; }, } @article {pmid25250196, year = {2014}, author = {Ramachandran, R and Radhan, P and Santosham, R and Rajendiran, S}, title = {A rare case of primary malignant pericardial mesothelioma.}, journal = {Journal of clinical imaging science}, volume = {4}, number = {}, pages = {47}, pmid = {25250196}, issn = {2156-7514}, abstract = {Primary malignant pericardial mesothelioma (PMPM) is a rare tumor of the pericardium. The cause of this tumor is unknown and it has a very poor prognosis. Exposure to asbestos is correlated with the onset of pleural and peritoneal mesothelioma; however, the role of asbestos in pericardial mesothelioma is unclear. Here we highlight the radiological features of this rare tumor and its correlative pathological confirmation with the help of new immunohistochemical (IHC) markers.}, } @article {pmid25238873, year = {2014}, author = {Gunatilake, S and Brims, FJ and Fogg, C and Lawrie, I and Maskell, N and Forbes, K and Rahman, N and Morris, S and Ogollah, R and Gerry, S and Peake, M and Darlison, L and Chauhan, AJ}, title = {A multicentre non-blinded randomised controlled trial to assess the impact of regular early specialist symptom control treatment on quality of life in malignant mesothelioma (RESPECT-MESO): study protocol for a randomised controlled trial.}, journal = {Trials}, volume = {15}, number = {}, pages = {367}, pmid = {25238873}, issn = {1745-6215}, mesh = {Affect ; Caregivers/psychology ; Clinical Protocols ; Cost of Illness ; Cost-Benefit Analysis ; Health Care Costs ; Health Resources/economics/statistics & numerical data ; Health Status ; Humans ; Lung Neoplasms/complications/diagnosis/economics/mortality/psychology/*therapy ; Mesothelioma/complications/diagnosis/economics/mortality/psychology/*therapy ; Mesothelioma, Malignant ; Palliative Care/economics/*methods ; Pleural Neoplasms/complications/diagnosis/economics/mortality/psychology/*therapy ; *Quality of Life ; *Referral and Consultation/economics ; *Research Design ; Surveys and Questionnaires ; Time Factors ; Treatment Outcome ; United Kingdom ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma is an incurable cancer caused by exposure to asbestos. The United Kingdom has the highest death rate from mesothelioma in the world and this figure is increasing. Median survival is 8 to 12 months, and most patients have symptoms at diagnosis. The fittest patients may be offered chemotherapy with palliative intent. For patients not fit for systemic anticancer treatment, best supportive care remains the mainstay of management. A study from the United States examining advanced lung cancer showed that early specialist palliative care input improved patient health related quality of life and depression symptoms 12 weeks after diagnosis. While mesothelioma and advanced lung cancer share many symptoms and have a poor prognosis, oncology and palliative care services in the United Kingdom, and many other countries, vary considerably compared to the United States. The aim of this trial is to assess whether regular early symptom control treatment provided by palliative care specialists can improve health related quality of life in patients newly diagnosed with mesothelioma.

METHODS: This multicentre study is an non-blinded, randomised controlled, parallel group trial. A total of 174 patients with a new diagnosis of malignant pleural mesothelioma will be minimised with a random element in a 1:1 ratio to receive either 4 weekly regular early specialist symptom control care, or standard care. The primary outcome is health related quality of life for patients at 12 weeks. Secondary outcomes include health related quality of life for patients at 24 weeks, carer health related quality of life at 12 and 24 weeks, patient and carer mood at 12 and 24 weeks, overall survival and analysis of healthcare utilisation and cost.

DISCUSSION: Current practice in the United Kingdom is to involve specialist palliative care towards the final weeks or months of a life-limiting illness. This study aims to investigate whether early, regular specialist care input can result in significant health related quality of life gains for patients with mesothelioma and if this change in treatment model is cost-effective. The results will be widely applicable to many institutions and patients both in the United Kingdom and internationally.

TRIAL REGISTRATION: Current controlled trials ISRCTN18955704. Date ISRCTN assigned: 31 January 2014.}, } @article {pmid25231672, year = {2015}, author = {Ortega-Guerrero, MA and Carrasco-Núñez, G and Barragán-Campos, H and Ortega, MR}, title = {High incidence of lung cancer and malignant mesothelioma linked to erionite fibre exposure in a rural community in Central Mexico.}, journal = {Occupational and environmental medicine}, volume = {72}, number = {3}, pages = {216-218}, doi = {10.1136/oemed-2013-101957}, pmid = {25231672}, issn = {1470-7926}, mesh = {Adult ; Carcinogens/*analysis/toxicity ; Environmental Exposure/adverse effects/*analysis ; Environmental Pollutants/*analysis/toxicity ; Female ; Humans ; Incidence ; Lung Neoplasms/etiology/*mortality ; Male ; Mesothelioma/etiology/*mortality ; Mesothelioma, Malignant ; Mexico/epidemiology ; Middle Aged ; Retrospective Studies ; Rural Population/*statistics & numerical data ; Soil Pollutants/adverse effects/analysis ; Zeolites/*analysis/toxicity ; }, abstract = {OBJECTIVE: To report the high incidence of lung cancer (LC) and malignant mesothelioma (MM) linked to environmental exposure to erionite fibres in a rural village of central Mexico.

METHODS: This is a retrospective survey of clinical and mortality records from the years 2000-2012, accompanied by an environmental survey for nine Group-1 lung and pleura carcinogenic agents listed by the International Agency for Research on Cancer (IARC).

RESULTS: Out of a total of 45 deaths between 2000 and 2012, 14 deaths correspond to different neoplasms of the lung, and at least four deaths to MM. The ages at diagnosis of MM were between 30 and 54 years. Annual age-standardised mortality rates per thousand due to LC and MM in the village (age >20 years) are 7.09 and 2.48 for males, and 4.75 and 1.05 for females, respectively. Erionite fibres were found in exposed rocks and soils, which can easily become airborne and be carried into streets and recreational areas near schools and homes. Other carcinogenic elements and minerals are found only in trace amounts, except for quartz dust and asbestos (chrysotile) cement sheeting, which are also present in the neighbouring villages.

CONCLUSIONS: These results indicate that environmental exposure to erionite is the main cause of the high rates of MM mortality in the Village of Tierra Blanca, supporting previous similar reports for people exposed to erionite fibres in villages in Turkey.}, } @article {pmid25231345, year = {2015}, author = {Betti, M and Casalone, E and Ferrante, D and Romanelli, A and Grosso, F and Guarrera, S and Righi, L and Vatrano, S and Pelosi, G and Libener, R and Mirabelli, D and Boldorini, R and Casadio, C and Papotti, M and Matullo, G and Magnani, C and Dianzani, I}, title = {Inference on germline BAP1 mutations and asbestos exposure from the analysis of familial and sporadic mesothelioma in a high-risk area.}, journal = {Genes, chromosomes & cancer}, volume = {54}, number = {1}, pages = {51-62}, doi = {10.1002/gcc.22218}, pmid = {25231345}, issn = {1098-2264}, mesh = {Adult ; Aged ; Asbestos/*toxicity ; Environmental Exposure/*adverse effects ; Environmental Pollutants/*toxicity ; Female ; *Germ-Line Mutation ; Humans ; Lung Neoplasms/chemically induced/*genetics ; Male ; Mesothelioma/chemically induced/*genetics ; Mesothelioma, Malignant ; Middle Aged ; Risk Factors ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {Inherited loss-of-function mutations in the BAP1 oncosuppressor gene are responsible for an inherited syndrome with predisposition to malignant mesothelioma (MM), uveal and keratinocytic melanoma, and other malignancies. Germline mutations that were inherited in an autosomal dominant fashion were identified in nine families with multiplex MM cases and 25 families with multiple melanoma, renal cell carcinoma, and other tumors. Germline mutations were also identified in sporadic MM cases, suggesting that germline mutations in BAP1 occur frequently. In this article, we report the analysis of BAP1 in five multiplex MM families and in 103 sporadic cases of MM. One family carried a new truncating germline mutation. Using immunohistochemistry, we show that BAP1 is not expressed in tumor tissue, which is in accordance with Knudson's two hits hypothesis. Interestingly, whereas the three individuals who were possibly exposed to asbestos developed MM, the individual who was not exposed developed a different tumor type, that is, mucoepidermoid carcinoma. This finding suggests that the type of carcinogen exposure may be important for the cancer type that is developed by mutation carriers. On the contrary, the other families or the 103 sporadic patients did not show germline mutations in BAP1. Our data show that BAP1 mutations are very rare in patients with sporadic MM, and we report a new BAP1 mutation, extend the cancer types associated with these mutations, and suggest the existence of other yet unknown genes in the pathogenesis of familial MM.}, } @article {pmid25217189, year = {2014}, author = {Mansfield, AS and Symanowski, JT and Peikert, T}, title = {Systematic review of response rates of sarcomatoid malignant pleural mesotheliomas in clinical trials.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {86}, number = {2}, pages = {133-136}, pmid = {25217189}, issn = {1872-8332}, support = {K23 CA159391/CA/NCI NIH HHS/United States ; UL1 TR000135/TR/NCATS NIH HHS/United States ; }, mesh = {Clinical Trials as Topic ; Combined Modality Therapy ; Humans ; Lung Neoplasms/*therapy ; Mesothelioma/*therapy ; Mesothelioma, Malignant ; Pleural Neoplasms/*therapy ; Treatment Outcome ; }, abstract = {RATIONALE: Malignant pleural mesothelioma is an almost universally fatal malignancy primarily related to asbestos exposure. Based on the differences in immunologic markers and gene expression between histologic subtypes of mesothelioma, and our clinical impression that response rates vary by histology, we decided to examine the reported response rates of mesothelioma subtypes.

OBJECTIVES: Our objective was to compare the response rates of sarcomatoid mesotheliomas to the overall response rates in published clinical trials.

METHODS: We searched PubMed for "mesothelioma" with the clinical trials filter selected. We included articles published between January 1, 2000 and March 20, 2014 in which subjects received first or second line systemic therapy for malignant pleural mesothelioma. Studies investigating multi-modality therapy including surgery were excluded. Response rates [including 95% confidence intervals (95% CI)] were estimated for the entire patient cohort and then separately for subjects with sarcomatoid tumors.

MEASUREMENTS AND MAIN RESULTS: We reviewed 544 publications of which 41 trials met our inclusion criteria. Eleven of these trials did not include patients with sarcomatoid mesothelioma (27% of eligible studies). The remaining 30 publications included 1475 subjects, 1011 with epithelioid tumors (68.5%), 203 with biphasic tumors (13.8%), 137 with sarcomatoid tumors (9.3%) and 124 with unknown subtypes (8.4%). In total, there were 323 responses (21.9%, complete and partial responses, 95% CI: 16.3, 28.8) to systemic therapy across all histological subtypes. In patients with sarcomatoid tumors (n=137) 19 responses were observed. This accounted for 5.9% of all responses and yields a 13.9% (95% CI: 8.6, 21.6) response rate for patients with sarcomatoid tumors. Multiple biases likely affected this systematic review.

CONCLUSION: Response rates for different histological subtypes of malignant pleural mesothelioma are infrequently reported. Partial and complete responses to systemic therapies appear to be less common among patients with sarcomatoid tumors.}, } @article {pmid25210967, year = {2014}, author = {Assis, LV and Isoldi, MC}, title = {Overview of the biochemical and genetic processes in malignant mesothelioma.}, journal = {Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia}, volume = {40}, number = {4}, pages = {429-442}, pmid = {25210967}, issn = {1806-3756}, mesh = {Carcinogenesis ; Humans ; Lung Neoplasms/*genetics/*metabolism ; Mesothelioma/*genetics/*metabolism ; Mesothelioma, Malignant ; Oncogenes ; }, abstract = {Malignant mesothelioma (MM) is a highly aggressive form of cancer, has a long latency period, and is resistant to chemotherapy. It is extremely fatal, with a mean survival of less than one year. The development of MM is strongly correlated with exposure to asbestos and with other factors, such as erionite and simian virus 40 [corrected]. Although various countries have banned the use of asbestos, MM has proven to be difficult to control and there appears to be a trend toward an increase in its incidence in the years to come. In Brazil, MM has not been widely studied from a genetic or biochemical standpoint. In addition, there have been few epidemiological studies of the disease, and the profile of its incidence has yet to be well established in the Brazilian population. The objective of this study was to review the literature regarding the processes of malignant transformation, as well as the respective mechanisms of tumorigenesis, in MM.}, } @article {pmid25208984, year = {2014}, author = {Lao, I and Chen, Q and Yu, L and Wang, J}, title = {[Sarcomatoid malignant mesothelioma: a clinicopathologic and immunohistochemical analysis of 22 cases].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {43}, number = {6}, pages = {364-369}, pmid = {25208984}, issn = {0529-5807}, mesh = {Adult ; Aged ; Biomarkers, Tumor/metabolism ; Carcinoma/diagnosis/pathology ; Diagnosis, Differential ; Humans ; Lung Neoplasms/diagnosis/*pathology ; Mesothelioma/diagnosis/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Prognosis ; Sarcoma/diagnosis/pathology ; Solitary Fibrous Tumors/diagnosis/pathology ; }, abstract = {OBJECTIVE: To elaborate on the clinical and pathologic features of sarcomatoid malignant mesothelioma (SMM), its diagnostic criteria and differential diagnoses.

METHODS: Twenty-two cases of SMM retrieved from in-house and consultation files (between January 2009 to September 2013) were reviewed with emphasis on the clinicopathologic characteristics, immunophenotypes and the prognostic impact.

RESULTS: The mean age of the patients was 54 years (ranged from 24-73 years). There was no sexual predilection and the majority of the patients did not have history of asbestos exposure. Overall, 14 tumors developed in the pleura and 8 cases arose from the peritoneal cavity. Clinically, patients presented signs and symptoms in accord with the location of the tumors, notably coughing, shortness of breath, and chest pain for patients with pleural origin, and nausea, abdominal distention and abdominal pain for those with peritoneal primary. In most cases, CT and MRI scan demonstrated lobulated masses (8/11). However, diffuse infiltrative growth patterns were observed exclusively in a minority of pleural cases (3/11). No visceral lesion was observed in any case. Histologically, 19 cases had either fibrosarcomatous or undifferentiated pleomorphic sarcoma-like appearance. Two cases were consistent with desmoplastic mesothelioma. One case contained osteosarcomatous element. All cases expressed pan-cytokeratin (AE1/AE3), and most cases were also positive for D2-40 (15/20). The staining of calretinin (9/21) and WT1 (10/14) was generally weak and focal. They were all negative for TTF-1, napsin A, SP-A, p63 and CD34. Follow-up information (range from 1 to 36 months) was available in 11 cases, 6 of which were alive with unresectable tumor, 1 patient with recurrent disease and 4 patients succumbed to disease. The overall survival was 5 months (mean 8 months).

CONCLUSIONS: The diagnosis of SMM is achieved by comprehensive evaluation of medical history, imageological and pathological findings. Since calretinin immunoreactivity is infrequently observed in SMM, application of pan-cytokeratin and D2-40 immunostains offers a reasonable alternative for diagnosis. Diagnosis of SMM can be made by excluding a variety of spindle cell neoplasms with overlapping features, such as sarcomatoid carcinoma, synovial sarcoma, solitary fibrous tumor and fibrous pleuritis.}, } @article {pmid25200195, year = {2014}, author = {Girardi, P and Bressan, V and Merler, E}, title = {Past trends and future prediction of mesothelioma incidence in an industrialized area of Italy, the Veneto Region.}, journal = {Cancer epidemiology}, volume = {38}, number = {5}, pages = {496-503}, doi = {10.1016/j.canep.2014.08.007}, pmid = {25200195}, issn = {1877-783X}, mesh = {Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Bayes Theorem ; Environmental Exposure/*adverse effects ; Female ; Humans ; Incidence ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology/etiology/pathology ; Middle Aged ; Pleural Neoplasms/*epidemiology/etiology/pathology ; Sex Distribution ; }, abstract = {BACKGROUND: Malignant Mesothelioma (MM) is so associated with (professional, familial or environmental) asbestos exposure that trends in incidence and mortality parallel, after 30-40 years, the trend in asbestos consumption. In recent decades, the industrialized countries have witnessed a steady growth of pleural MM (MPM), following a stabilization or decline in rates in the countries that first adopted restrictive policies. The aim of this study was to evaluate the temporal variations of pleural MM incidence in the Veneto Region of Italy in the period 1987-2010.

METHODS: We included only MPM with histological or cytological diagnosis. Age-Period-Cohort (APC) models were used to assess the trend in the incidence of MPM in both genders. Future predictions were evaluated by using a Bayesian APC model.

RESULTS: In the period 1987-2010, 1600 MPMs have occurred. We observe a positive trend in the incidence in the whole period considered. The APC model showed that in both genders the cohort at higher risk is the one born between the years 1940-1945. Future projections indicate that the trend will decrease after the incidence peak of 2010; yet 1234 men are expected to develop a mesothelioma between 2011 and 2026. Among women, the future MPM rates will be stable or slightly decreasing.

CONCLUSIONS: The asbestos ban introduced in Italy in the year 1992 as a prospective result will certainly determine a decreasing incidence. However, the extremely long latency of MPM means that its influence is not yet observable.}, } @article {pmid25188816, year = {2014}, author = {Schelch, K and Hoda, MA and Klikovits, T and Münzker, J and Ghanim, B and Wagner, C and Garay, T and Laszlo, V and Setinek, U and Dome, B and Filipits, M and Pirker, C and Heffeter, P and Selzer, E and Tovari, J and Torok, S and Kenessey, I and Holzmann, K and Grasl-Kraupp, B and Marian, B and Klepetko, W and Berger, W and Hegedus, B and Grusch, M}, title = {Fibroblast growth factor receptor inhibition is active against mesothelioma and synergizes with radio- and chemotherapy.}, journal = {American journal of respiratory and critical care medicine}, volume = {190}, number = {7}, pages = {763-772}, doi = {10.1164/rccm.201404-0658OC}, pmid = {25188816}, issn = {1535-4970}, mesh = {Animals ; Antineoplastic Agents/pharmacology ; Apoptosis/drug effects/genetics ; Cell Line, Tumor ; Cell Proliferation/drug effects/genetics ; Cell Survival/drug effects/genetics ; Cisplatin/pharmacology ; Combined Modality Therapy/methods ; Disease Models, Animal ; Humans ; Lung Neoplasms/*drug therapy/genetics/*radiotherapy ; Mesothelioma/*drug therapy/genetics/*radiotherapy ; Mesothelioma, Malignant ; Mice ; Protein Kinase Inhibitors/*pharmacology ; Receptor, Fibroblast Growth Factor, Type 1/*antagonists & inhibitors/drug effects/genetics ; Signal Transduction/drug effects/genetics ; }, abstract = {RATIONALE: Malignant pleural mesothelioma is an aggressive malignancy characterized by frequent resistance to chemo- and radiotherapy, poor outcome, and limited therapeutic options. Fibroblast growth factors (FGFs) and their receptors are potential targets for cancer therapy, but their significance in mesothelioma has remained largely undefined.

OBJECTIVES: To investigate the antimesothelioma potential of FGF receptor 1 (FGFR1) inhibition.

METHODS: Expression of FGFs and their receptors was analyzed in mesothelioma cell lines and tissue specimens. Several cell models were used to investigate FGFR1 inhibition in vitro and in combination with cisplatin and irradiation. Mouse intraperitoneal xenotransplant models were used for in vivo validation.

MEASUREMENTS AND MAIN RESULTS: FGFR1, FGF2, and FGF18 were overexpressed in mesothelioma. Stimulation with FGF2 led to increased cell proliferation, migration, and transition to a more sarcomatoid phenotype in subsets of mesothelioma cell lines. In contrast, inhibition of FGFR1 by a specific kinase inhibitor or a dominant-negative FGFR1 construct led to significantly decreased proliferation, clonogenicity, migration, spheroid formation, and G1 cell cycle arrest in several mesothelioma cell lines, accompanied by apoptosis induction and decreased mitogen-activated protein kinase pathway activity. Reduced tumor growth, proliferation, mitogenic signaling, and apoptosis induction were observed in vivo. Inhibition of FGFR1 synergistically enhanced the cytotoxic effects of ionizing radiation and cisplatin.

CONCLUSIONS: Our data suggest that the malignant phenotype of mesothelioma cells depends on intact FGF signals, which should be considered as therapeutic targets with a promising chemo- and radiosensitizing potential.}, } @article {pmid25188323, year = {2014}, author = {Linton, A and Pavlakis, N and O'Connell, R and Soeberg, M and Kao, S and Clarke, S and Vardy, J and van Zandwijk, N}, title = {Factors associated with survival in a large series of patients with malignant pleural mesothelioma in New South Wales.}, journal = {British journal of cancer}, volume = {111}, number = {9}, pages = {1860-1869}, pmid = {25188323}, issn = {1532-1827}, mesh = {Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/*mortality/pathology/therapy ; Lymphocytes/pathology ; Male ; Mesothelioma/*mortality/pathology/therapy ; Mesothelioma, Malignant ; Neoplasm Staging ; Neutrophils/pathology ; New South Wales ; Pleural Neoplasms/*mortality/pathology/therapy ; Pneumonectomy/*mortality ; Prognosis ; Survival Rate ; }, abstract = {BACKGROUND: Although the prognosis of most patients presenting with malignant pleural mesothelioma (MPM) is poor, a small proportion survives long term. We investigated factors associated with survival in a large patient series.

METHODS: All patients registered with the NSW Dust Diseases Board (2002-2009) were included in an analysis of prognostic factors using Kaplan-Meier and Cox regression analysis. On the basis of these analyses, we developed a risk score (Prognostic Index (PI)).

RESULTS: We identified 910 patients: 90% male; histology (epithelioid 60%; biphasic 13%; sarcomatoid 17%); stage (Tx-I-II 48%; III-IV 52%); and calretinin expression (91%).

TREATMENT: chemotherapy(CT) 44%, and extrapleural-pneumonectomy (EPP) 6%. Median overall survival (OS) was 10.0 months. Longer OS was associated with: age <70 (13.5 vs 8.5 months; P<0.001); female gender (12.0 vs 9.9 months; P<0.001); epithelioid subtype (13.3 vs 6.2 months; P<0.001); ECOG status 0 (27.4 vs 9.7 months; P=0.015), calretinin expression (10.9 vs 5.5 months; P<0.001); neutrophil-lymphocyte ratio (NLR) <5 (11.9 vs 7.5 months; P<0.001); platelet count <400 (11.5 vs 7.2 months; P<0.001); and normal haemoglobin (16.4 vs 8.8 months; P<0.001). On time-dependent analysis, patients receiving pemetrexed-based chemotherapy (HR=0.83; P=0.048) or EPP (HR=0.41; P<0.001) had improved survival. Age, gender, histology, calretinin and haematological factors remained significant on multivariate analysis. In all, 24% of patients survived >20 months: 16% of these receiving EPP, and 66% CT. The PI offered improved prognostic discrimination over one of the existing prognostic models (EORTC).

CONCLUSIONS: We identified calretinin expression, age, gender, histological subtype, platelet count and haemoglobin level as independent prognostic factors. Patients undergoing EPP or pemetrexed-based chemotherapy demonstrated better survival, but 84% and 34% of long survivors, respectively, did not receive radical surgery or chemotherapy.}, } @article {pmid25186542, year = {2014}, author = {Langhoff, MD and Kragh-Thomsen, MB and Stanislaus, S and Weinreich, UM}, title = {Almost half of women with malignant mesothelioma were exposed to asbestos at home through their husbands or sons.}, journal = {Danish medical journal}, volume = {61}, number = {9}, pages = {A4902}, pmid = {25186542}, issn = {2245-1919}, mesh = {Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Denmark/epidemiology ; Environmental Exposure/*adverse effects/statistics & numerical data ; Environmental Pollutants/*toxicity ; Female ; Humans ; Kaplan-Meier Estimate ; Lung Neoplasms/diagnosis/epidemiology/*etiology/mortality ; Male ; Mesothelioma/diagnosis/epidemiology/*etiology/mortality ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/adverse effects/statistics & numerical data ; Pleural Neoplasms/diagnosis/epidemiology/*etiology/mortality ; Retrospective Studies ; Spouses ; Survival Rate ; }, abstract = {INTRODUCTION: Women often develop malignant mesothelioma (MM) without occupational asbestos exposure. Northern Jutland has a high prevalence of MM due to previously high occupational exposures to asbestos. The aim of this study was to elucidate a possible domestic exposure to asbestos through first-degree relatives in women who develop MM.

MATERIAL AND METHODS: This was a retrospective study in women with MM of the pleura. A total of 30 women were diagnosed with and treated for MM in Northern Jutland from 1996 to 2012. In all, 24 women were included. Demographic data, subtype of MM, time from first hospital contact to diagnosis, survival and information on occupational and domestic exposure to asbestos were obtained from hospital records.

RESULTS: A total of 12.5% of the study population were primarily exposed to asbestos. 46% had domestic exposure to asbestos through their husbands or sons. The median age of the study population was 66.5 years. In all, 75% suffered from the epitheloid subtype, 12.5% from the biphasic and 8.4% from the sarcomatoid subtype. Time from first hospital contact to diagnosis was one month and the median survival time was 12 months. The 1- and 5- year-survival were 58% and 0%, respectively.

CONCLUSION: Nearly 50% of the women affected by MM have been domestically exposed to asbestos through first-degree relatives.

FUNDING: not relevant.

TRIAL REGISTRATION: not relevant.}, } @article {pmid25185462, year = {2014}, author = {Gordon, RE and Fitzgerald, S and Millette, J}, title = {Asbestos in commercial cosmetic talcum powder as a cause of mesothelioma in women.}, journal = {International journal of occupational and environmental health}, volume = {20}, number = {4}, pages = {318-332}, pmid = {25185462}, issn = {2049-3967}, mesh = {Asbestos/analysis/*toxicity ; Cosmetics/*toxicity ; Female ; Humans ; Inhalation Exposure/adverse effects ; Mesothelioma/*chemically induced ; Microscopy, Electron, Scanning ; Microscopy, Electron, Transmission ; Pleural Neoplasms/chemically induced ; Talc/chemistry/*toxicity ; }, abstract = {BACKGROUND: Cosmetic talcum powder products have been used for decades. The inhalation of talc may cause lung fibrosis in the form of granulomatose nodules called talcosis. Exposure to talc has also been suggested as a causative factor in the development of ovarian carcinomas, gynecological tumors, and mesothelioma.

PURPOSE: To investigate one historic brand of cosmetic talcum powder associated with mesothelioma in women.

METHODS: Transmission electron microscope (TEM) formvar-coated grids were prepared with concentrations of one brand of talcum powder directly, on filters, from air collections on filters in glovebox and simulated bathroom exposures and human fiber burden analyses. The grids were analyzed on an analytic TEM using energy-dispersive spectrometer (EDS) and selected-area electron diffraction (SAED) to determine asbestos fiber number and type.

RESULTS: This brand of talcum powder contained asbestos and the application of talcum powder released inhalable asbestos fibers. Lung and lymph node tissues removed at autopsy revealed pleural mesothelioma. Digestions of the tissues were found to contain anthophyllite and tremolite asbestos.

DISCUSSION: Through many applications of this particular brand of talcum powder, the deceased inhaled asbestos fibers, which then accumulated in her lungs and likely caused or contributed to her mesothelioma as well as other women with the same scenario.}, } @article {pmid25175318, year = {2014}, author = {Robinson, C and Alfonso, H and Woo, S and Olsen, N and Bill Musk, AW and Robinson, BW and Nowak, AK and Lake, RA}, title = {Effect of NSAIDS and COX-2 inhibitors on the incidence and severity of asbestos-induced malignant mesothelioma: evidence from an animal model and a human cohort.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {86}, number = {1}, pages = {29-34}, doi = {10.1016/j.lungcan.2014.08.005}, pmid = {25175318}, issn = {1872-8332}, mesh = {Aged ; Animals ; *Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Asbestos/*adverse effects ; Aspirin/therapeutic use ; Chemoprevention ; Cohort Studies ; *Cyclooxygenase 2 Inhibitors/therapeutic use ; Disease Models, Animal ; Female ; Humans ; Incidence ; Lung Neoplasms/*chemically induced/drug therapy/*epidemiology/prevention & control ; Male ; Mesothelioma/*chemically induced/drug therapy/*epidemiology/prevention & control ; Mesothelioma, Malignant ; Mice ; Mice, Transgenic ; Middle Aged ; Risk Factors ; Severity of Illness Index ; Survival Analysis ; Western Australia/epidemiology ; }, abstract = {OBJECTIVES: Non-steroidal anti-inflammatory drugs (NSAIDs) and COX-2 inhibitors have been associated with lower incidence rates of some cancers. Because asbestos can cause chronic inflammation at the pleural and peritoneal surfaces we hypothesised that NSAID and COX-2 inhibitors would inhibit the development of asbestos-induced mesothelioma.

MATERIALS AND METHODS: A murine model of asbestos-induced mesothelioma was used to test this hypothesis by providing the NSAID, aspirin, daily in the feed at 50mg/kg or 250 mg/kg. In a parallel study, the relationship between the use of NSAID and COX-2 inhibitors and mesothelioma was investigated in a human cohort of 1738 asbestos exposed people living or working in Wittenoom, Western Australia (a crocidolite mine site).

RESULTS: Aspirin did not alter the rate of disease development or increase the length of time that mice survived. Aspirin had a small but significant effect on disease latency (the time between asbestos exposure and first evidence of disease; p<0.05) but disease progression was not affected by the continued presence of the drug. In the Wittenoom cohort, individuals who reported use of NSAIDs, COX-2 inhibitors or both did not have a lower incidence of mesothelioma (HR=0.85; 95% CI=0.53-1.37, p=0.50), (HR=0.69; 95% CI=0.21-2.30, p=0.55) and (HR=0.43; 95% CI=0.16-1.13, p=0.087) respectively.

CONCLUSION: We conclude that NSAIDs and COX-2 inhibitors do not moderate mesothelioma development or progression in a human cohort exposed to asbestos and this result is confirmed in an autochthonous mouse model.}, } @article {pmid25175133, year = {2014}, author = {Kanbay, A and Ozer Simsek, Z and Tutar, N and Yılmaz, I and Buyukoglan, H and Canoz, O and Demir, R}, title = {Non-asbestos-related malignant pleural mesothelioma.}, journal = {Internal medicine (Tokyo, Japan)}, volume = {53}, number = {17}, pages = {1977-1979}, doi = {10.2169/internalmedicine.53.0900}, pmid = {25175133}, issn = {1349-7235}, mesh = {Asbestos ; Biopsy ; Diagnosis, Differential ; Humans ; Lung Neoplasms/*diagnosis/surgery ; Male ; Mesothelioma/*diagnosis/surgery ; Mesothelioma, Malignant ; Neoplasm Grading ; Pleura/pathology ; Pleural Neoplasms/*diagnosis/surgery ; Radiography, Thoracic ; Thoracic Surgery, Video-Assisted/methods ; Tomography, X-Ray Computed ; }, abstract = {Malignant pleural mesothelioma (MPM) is an uncommon tumor derived from mesothelial lining cells. MPM has been described as an insidious neoplasm because of its long latency period. The tumor is typically found in patients several decades after asbestos exposure. We herein describe a 26-year-old patient with MPM who presented with pleural effusion. The patient had not been exposed to asbestos or erionite. There are few case reports of non-asbestos-related MPM in young patients. We report this case to remind physicians to consider MPM in the differential diagnosis of pleural effusion in young patients without exposure to asbestos or erionitis.}, } @article {pmid25169088, year = {2014}, author = {Ma, Q and Cao, C and Hong, X}, title = {[Diagnosis and analysis of asbestos induced peritoneal mesothelioma].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {32}, number = {5}, pages = {347}, pmid = {25169088}, issn = {1001-9391}, mesh = {Asbestos/*adverse effects ; Humans ; Mesothelioma/chemically induced/*diagnosis ; Peritoneal Neoplasms/chemically induced/*diagnosis ; }, } @article {pmid25168068, year = {2014}, author = {Lippmann, M}, title = {Toxicological and epidemiological studies on effects of airborne fibers: coherence and public [corrected] health implications.}, journal = {Critical reviews in toxicology}, volume = {44}, number = {8}, pages = {643-695}, doi = {10.3109/10408444.2014.928266}, pmid = {25168068}, issn = {1547-6898}, support = {ES 00260/ES/NIEHS NIH HHS/United States ; }, mesh = {Air Pollutants/chemistry/pharmacokinetics/*toxicity ; Animals ; Asbestos, Serpentine/chemistry/toxicity ; Epidemiologic Studies ; Humans ; Inhalation Exposure/*adverse effects ; Lung Neoplasms/chemically induced/epidemiology ; Mesothelioma/chemically induced/epidemiology ; Particulate Matter/pharmacokinetics/*toxicity ; Public Health ; Pulmonary Fibrosis/chemically induced/epidemiology ; Risk Assessment ; Solubility ; }, abstract = {Airborne fibers, when sufficiently biopersistent, can cause chronic pleural diseases, as well as excess pulmonary fibrosis and lung cancers. Mesothelioma and pleural plaques are caused by biopersistent fibers thinner than ∼0.1 μm and longer than ∼5 μm. Excess lung cancer and pulmonary fibrosis are caused by biopersistent fibers that are longer than ∼20 μm. While biopersistence varies with fiber type, all amphibole and erionite fibers are sufficiently biopersistent to cause pathogenic effects, while the greater in vivo solubility of chrysotile fibers makes them somewhat less causal for the lung diseases, and much less causal for the pleural diseases. Most synthetic vitreous fibers are more soluble in vivo than chrysotile, and pose little, if any, health pulmonary or pleural health risk, but some specialty SVFs were sufficiently biopersistent to cause pathogenic effects in animal studies. My conclusions are based on the following: 1) epidemiologic studies that specified the origin of the fibers by type, and especially those that identified their fiber length and diameter distributions; 2) laboratory-based toxicologic studies involving fiber size characterization and/or dissolution rates and long-term observation of biological responses; and 3) the largely coherent findings of the epidemiology and the toxicology. The strong dependence of effects on fiber diameter, length, and biopersistence makes reliable routine quantitative exposure and risk assessment impractical in some cases, since it would require transmission electronic microscopic examination, of representative membrane filter samples, for determining statistically sufficient numbers of fibers longer than 5 and 20 μm, and those thinner than 0.1 μm, based on the fiber types.}, } @article {pmid25166502, year = {2014}, author = {Frassy, F and Candiani, G and Rusmini, M and Maianti, P and Marchesi, A and Rota Nodari, F and Dalla Via, G and Albonico, C and Gianinetto, M}, title = {Mapping asbestos-cement roofing with hyperspectral remote sensing over a large mountain region of the Italian Western Alps.}, journal = {Sensors (Basel, Switzerland)}, volume = {14}, number = {9}, pages = {15900-15913}, pmid = {25166502}, issn = {1424-8220}, mesh = {Adhesives/*analysis ; Aircraft/*instrumentation ; Altitude ; Asbestos/*analysis ; Construction Materials/*analysis ; Environmental Monitoring/*instrumentation ; Equipment Design ; Equipment Failure Analysis ; *Geographic Mapping ; Italy ; Remote Sensing Technology/*instrumentation ; }, abstract = {The World Health Organization estimates that 100 thousand people in the world die every year from asbestos-related cancers and more than 300 thousand European citizens are expected to die from asbestos-related mesothelioma by 2030. Both the European and the Italian legislations have banned the manufacture, importation, processing and distribution in commerce of asbestos-containing products and have recommended action plans for the safe removal of asbestos from public and private buildings. This paper describes the quantitative mapping of asbestos-cement covers over a large mountainous region of Italian Western Alps using the Multispectral Infrared and Visible Imaging Spectrometer sensor. A very large data set made up of 61 airborne transect strips covering 3263 km2 were processed to support the identification of buildings with asbestos-cement roofing, promoted by the Valle d'Aosta Autonomous Region with the support of the Regional Environmental Protection Agency. Results showed an overall mapping accuracy of 80%, in terms of asbestos-cement surface detected. The influence of topography on the classification's accuracy suggested that even in high relief landscapes, the spatial resolution of data is the major source of errors and the smaller asbestos-cement covers were not detected or misclassified.}, } @article {pmid25162674, year = {2014}, author = {Comar, M and Zanotta, N and Bonotti, A and Tognon, M and Negro, C and Cristaudo, A and Bovenzi, M}, title = {Increased levels of C-C chemokine RANTES in asbestos exposed workers and in malignant mesothelioma patients from an hyperendemic area.}, journal = {PloS one}, volume = {9}, number = {8}, pages = {e104848}, pmid = {25162674}, issn = {1932-6203}, mesh = {Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Biomarkers, Tumor/blood/*genetics ; Case-Control Studies ; Chemokine CCL5/blood/*genetics ; Cytokines/blood/genetics ; *Endemic Diseases ; Gene Expression ; Gene Expression Profiling ; Humans ; Lung Neoplasms/blood/diagnosis/etiology/*genetics ; Mesothelioma/blood/diagnosis/etiology/*genetics ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/*adverse effects ; Simian virus 40/genetics ; Viral Proteins/blood/*genetics ; }, abstract = {BACKGROUND: Asbestos-induced mesothelial inflammatory processes are thought to be the basic mechanisms underlying Malignant Mesothelioma (MM) development. Detection of MM often occurs at late stage due to the long and unpredictable latent period and the low incidence in asbestos exposed individuals. The aim of this study was to investigate early immunological biomarkers to characterize the prognostic profile of a possible asbestos-induced disease, in subjects from a MM hyperendemic area.

METHODS: The Luminex Multiplex Panel Technology was used for the simultaneous measurement of serum levels of a large panel of 47 analytes, including cytokines and growth factors, from workers previously exposed to asbestos (Asb-workers), asbestos-induced MM patients and healthy subjects. In addition, to explore the influence on serum cytokines profile exerted by SV40 infection, a cofactor in MM development, a quantitative real time PCR was performed for sequences detection in the N-terminal and intronic regions of the SV40 Tag gene. Statistical analysis was done by means of the Mann-Whitney test and the Kruskall-Wallis test for variance analysis.

RESULTS: A variety of 25 cytokines linked to pulmonary inflammation and tumor development were found significantly associated with Asb-workers and MM patients compared with healthy controls. A specific pattern of cytokines were found highly expressed in Asb-workers: IFN-alpha (p<0.05), EOTAXIN (p<0.01), RANTES (p<0.001), and in MM patients: IL-12(p40), IL-3, IL-1 alpha, MCP-3, beta-NGF, TNF-beta, RANTES (p<0.001). Notably, the chemokine RANTES measured the highest serum level showing an increased gradient of concentration from healthy subjects to Asb-workers and MM patients (p<0.001), independently of SV40 infection.

CONCLUSION: This study shows that, in subjects from an hyperendemic area for MM, the C-C chemokine RANTES is associated with the exposure to asbestos fibres. If validated in larger samples, this factor could have the potential to be a critical biomarker for MM prognosis as recently reported for breast tumor.}, } @article {pmid25161804, year = {2014}, author = {Singhal, B and Kohli, S and Singhal, A and Kumar, V}, title = {Malignant pleural and peritoneal mesothelioma consequential to brief indirect asbestos exposure.}, journal = {Journal of clinical imaging science}, volume = {4}, number = {}, pages = {35}, pmid = {25161804}, issn = {2156-7514}, abstract = {This report highlights that pleural and peritoneal mesothelioma can occur without direct asbestos exposure as was seen in our young patient. The patient had indirect exposure for as short as 3 months as a child, 15 years earlier, when she was residing with her miner father in the district of Jharia, Jharkhand, which is an asbestos-rich mining area in eastern India. The patient presented with chest pain and breathlessness. Chest X-ray showed opaque right hemithorax. Typical contrast- computed tomography (CECT) enhanced radiological features included nodular, soft-tissue attenuation and homogenously enhancing rind-like mass causing scalloping of the underlying lung and liver. Similar lesions were also found involving the pelvis. Diagnosis of malignant mesothelioma was confirmed on lung biopsy. Under-reporting of exposure is usual because it is unrecognized by both patients and investigators.}, } @article {pmid25135741, year = {2014}, author = {Lee, S and Matsuzaki, H and Kumagai-Takei, N and Yoshitome, K and Maeda, M and Chen, Y and Kusaka, M and Urakami, K and Hayashi, H and Fujimoto, W and Nishimura, Y and Otsuki, T}, title = {Silica exposure and altered regulation of autoimmunity.}, journal = {Environmental health and preventive medicine}, volume = {19}, number = {5}, pages = {322-329}, pmid = {25135741}, issn = {1347-4715}, mesh = {Autoimmunity/*drug effects ; *Construction Industry ; Humans ; Japan ; Lymphocytes/drug effects/immunology ; *Occupational Exposure ; Silicon Dioxide/*toxicity ; Silicosis/blood/etiology/*immunology ; }, abstract = {Silica particles and asbestos fibers, which are known as typical causatives of pneumoconiosis, induce lung fibrosis. Moreover, silicosis patients often complicate with autoimmune diseases, and asbestos-exposed patients suffer from malignant diseases such as pleural mesothelioma and lung cancer. We have been conducting experimental studies to investigate altered regulation of self-tolerance caused by silica exposure, including analyses using specimens such as plasma and immunocompetent cells obtained from silicosis patients, as a means of examining the supposition that silica exposure induces molecular and cellular biological alterations of immune cells. These approaches have resulted in the detection of several specific autoantibodies, alterations of CD95/Fas and its related molecules, and evidence of chronic activation of responder T cells and regulatory T cells following silica exposure. In this review, we present details of our investigations as an introduction to scientific approaches examining the immunological effects of environmental and occupational substances.}, } @article {pmid25134629, year = {2014}, author = {Mastrangelo, G and Fadda, E and Comiati, V and Dell'Aquila, M and Zamprogno, E and Fedeli, U and Bellini, E}, title = {A rare occupation causing mesothelioma: mechanisms and differential etiology.}, journal = {La Medicina del lavoro}, volume = {105}, number = {5}, pages = {337-345}, pmid = {25134629}, issn = {0025-7818}, mesh = {Aged ; Asbestos/*adverse effects ; Asbestos, Crocidolite/adverse effects ; Asbestos, Serpentine/adverse effects ; *Carcinogens ; Fatal Outcome ; Humans ; Italy ; Lung Neoplasms/*etiology ; Maintenance ; Male ; Mesothelioma/*etiology ; Occupational Exposure/*adverse effects ; *Railroads ; Risk Assessment ; }, abstract = {BACKGROUND: In a mesothelioma lawsuit, the Public Prosecutor commissioned an expert evidence on the legal accountability for the disease, because the patient experienced multiple exposures to asbestos in both occupational and environmental settings.

OBJECTIVES: To collect information on asbestos exposure from all available sources and to quantify the contribution of each source of exposure as a percentage of the total risk.

METHODS: We retrieved information on jobs done and asbestos exposure from a work colleague and a database maintained by the National Institute for Insurance of Occupational Accidents/Diseases, respectively. Information on environmental exposure was searched through the scientific literature. The contribution of each source of exposure was quantified with a method of risk apportionment, taking into account time elapsed since first and last exposure, intensity and frequency of exposure and carcinogenic potency of asbestos fiber mix.

RESULTS: The subject worked in the maintenance of railway electrification system. The mechanical compression stress induced on the ballast during passage of trains released chrysotile (from fragmented stones) and crocidolite (through abrasive action of crushed gravel on the underbody of rolling stocks insulated with friable crocidolite). Despite the low cumulative exposure (about 2 ff×years/cc), 99% of the mesothelioma risk was attributable to the work done because of the high content of crocidolite of inhaled asbestos.

CONCLUSIONS: The report of an uncommon source of occupational asbestos exposure and a scientifically based method to allocate mesothelioma risk among multiple exposure could help to recognize mesothelioma as occupational disease in the workers employed in maintenance of the railway electrification system under the Italian National Railways.}, } @article {pmid25132032, year = {2014}, author = {Yagi, Y and Maeda, T and Yoshimitsu, Y and Sakuma, H}, title = {[A case of malignant peritoneal mesothelioma diagnosed with laparoscopic biopsy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {41}, number = {8}, pages = {995-997}, pmid = {25132032}, issn = {0385-0684}, mesh = {Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Ascites/etiology ; Biopsy ; Carboplatin/administration & dosage ; Female ; Glutamates/administration & dosage ; Guanine/administration & dosage/analogs & derivatives ; Humans ; Laparoscopy ; Lung Neoplasms/complications/drug therapy/*pathology ; Mesothelioma/complications/drug therapy/*pathology ; Mesothelioma, Malignant ; Pemetrexed ; Peritoneal Neoplasms/complications/drug therapy/*pathology ; }, abstract = {A 66-year-old woman was admitted to our hospital for massive ascites of unknown origin. Peritoneal mesothelioma was suspected because of her history of asbestos exposure. Diagnostic laparoscopy with biopsy of the peritoneum and greater omentum was performed. Pathological examination with immunostaining provided a definite diagnosis of malignant peritoneal mesothelioma. The patient underwent early postoperative induction therapy with pemetrexed and carboplatin, which resulted in a reduction in ascites. Laparoscopic biopsy contributed to the definite diagnosis of malignant peritoneal mesothelioma, and thereby, early induction of chemotherapy.}, } @article {pmid25130001, year = {2014}, author = {Aierken, D and Okazaki, Y and Chew, SH and Sakai, A and Wang, Y and Nagai, H and Misawa, N and Kohyama, N and Toyokuni, S}, title = {Rat model demonstrates a high risk of tremolite but a low risk of anthophyllite for mesothelial carcinogenesis.}, journal = {Nagoya journal of medical science}, volume = {76}, number = {1-2}, pages = {149-160}, pmid = {25130001}, issn = {0027-7622}, mesh = {Animals ; Asbestos, Amphibole/chemistry/*toxicity ; Carcinogenicity Tests ; Cell Transformation, Neoplastic/*chemically induced/pathology ; Female ; Lung Neoplasms/*chemically induced/pathology/prevention & control ; Male ; Mesothelioma/*chemically induced/pathology/prevention & control ; Mesothelioma, Malignant ; Nitrilotriacetic Acid/toxicity ; Particle Size ; Rats ; Rats, Inbred BN ; Rats, Inbred F344 ; Risk Assessment ; Risk Factors ; Sex Factors ; Time Factors ; }, abstract = {Asbestos was abundantly used in industry during the last century. Currently, asbestos confers a heavy social burden due to an increasing number of patients with malignant mesothelioma (MM), which develops after a long incubation period. Many studies have been conducted on the effects of the asbestos types that were most commonly used for commercial applications. However, there are few studies describing the effects of the less common types, or minor asbestos. We performed a rat carcinogenesis study using Japanese tremolite and Afghan anthophyllite. Whereas more than 50% of tremolite fibers had a diameter of < 500 nm, only a small fraction of anthophyllite fibers had a diameter of < 500 nm. We intraperitoneally injected 1 or 10 mg of asbestos into F1 Fischer-344/Brown-Norway rats. In half of the animals, repeated intraperitoneal injections of nitrilotriacetate (NTA), an iron chelator to promote Fenton reaction, were performed to evaluate the potential involvement of iron overload. Tremolite induced MM with a high incidence (96% with 10 mg; 52% with 1 mg), and males were more susceptible than females. Histology was confirmed using immunohistochemistry, and most MMs were characterized as the sarcomatoid or biphasic subtype. Unexpectedly NTA showed an inhibitory effect in females. In contrast, anthophyllite induced no MM after an observation period of 550 days. The results suggest that the carcinogenicity of anthophyllite is weaker than formerly reported, whereas that of tremolite is as potent as major asbestos as compared with our previous data.}, } @article {pmid25120691, year = {2014}, author = {Ohnishi, Y and Sugitatsu, M and Watanabe, M and Fujii, T and Kakudo, K}, title = {Metastasis of mesothelioma to the maxillary gingiva.}, journal = {Oncology letters}, volume = {8}, number = {3}, pages = {1214-1216}, pmid = {25120691}, issn = {1792-1074}, abstract = {Malignant mesothelioma predominantly arises from the serosal surfaces of the pleural or peritoneal cavity. There is currently no effective standard treatment for mesothelioma and the prognosis for patients is poor; the majority of patients with malignant mesothelioma succumb between 12 and 17 months following diagnosis. The association of all forms of malignant mesothelioma with asbestos exposure has been well documented. However, metastasis to the oral gingiva is rare, as only four cases have previously been reported; two cases of metastasis to the tongue and four cases to the jaw bone. In the current report, the case of a 62-year-old male with metastatic mesothelioma is presented. To the best of our knowledge, this is the first report regarding the metastasis of this type of neoplasm to the maxillary gingiva.}, } @article {pmid25111229, year = {2014}, author = {Westbom, CM and Shukla, A and MacPherson, MB and Yasewicz, EC and Miller, JM and Beuschel, SL and Steele, C and Pass, HI and Vacek, PM and Shukla, A}, title = {CREB-induced inflammation is important for malignant mesothelioma growth.}, journal = {The American journal of pathology}, volume = {184}, number = {10}, pages = {2816-2827}, pmid = {25111229}, issn = {1525-2191}, support = {P20 GM103449/GM/NIGMS NIH HHS/United States ; R01 ES021110/ES/NIEHS NIH HHS/United States ; P30 CA016087/CA/NCI NIH HHS/United States ; T32 ES007122/ES/NIEHS NIH HHS/United States ; P20GM103449/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Asbestos/adverse effects ; CREB-Binding Protein/*metabolism ; Cell Line, Tumor ; Chemokine CCL2/metabolism ; Chemokines/metabolism ; Disease Models, Animal ; Doxorubicin/pharmacology ; Gene Expression Profiling ; Heterografts ; Humans ; Inflammation ; Interleukin-6/metabolism ; Interleukin-8/metabolism ; Lung Neoplasms/metabolism/*pathology ; Male ; Mesothelioma/metabolism/*pathology ; Mesothelioma, Malignant ; Mice ; Mice, SCID ; Oligonucleotide Array Sequence Analysis ; Phosphorylation ; Vascular Endothelial Growth Factor A/metabolism ; }, abstract = {Malignant mesothelioma (MM) is an aggressive tumor with no treatment regimen. Previously we have demonstrated that cyclic AMP response element binding protein (CREB) is constitutively activated in MM tumor cells and tissues and plays an important role in MM pathogenesis. To understand the role of CREB in MM tumor growth, we generated CREB-inhibited MM cell lines and performed in vitro and in vivo experiments. In vitro experiments demonstrated that CREB inhibition results in significant attenuation of proliferation and drug resistance of MM cells. CREB-silenced MM cells were then injected into severe combined immunodeficiency mice, and tumor growth in s.c. and i.p. models of MM was followed. We observed significant inhibition in MM tumor growth in both s.c. and i.p. models and the presence of a chemotherapeutic drug, doxorubicin, further inhibited MM tumor growth in the i.p. model. Peritoneal lavage fluids from CREB-inhibited tumor-bearing mice showed a significantly reduced total cell number, differential cell counts, and pro-inflammatory cytokines and chemokines (IL-6, IL-8, regulated on activation normal T cell expressed and secreted, monocyte chemotactic protein-1, and vascular endothelial growth factor). In vitro studies showed that asbestos-induced inflammasome/inflammation activation in mesothelial cells was CREB dependent, further supporting the role of CREB in inflammation-induced MM pathogenesis. In conclusion, our data demonstrate the involvement of CREB in the regulation of MM pathogenesis by regulation of inflammation.}, } @article {pmid25093718, year = {2014}, author = {Robinson, C and Alfonso, H and Woo, S and Walsh, A and Olsen, N and Musk, AW and Robinson, BW and Nowak, AK and Lake, RA}, title = {Statins do not alter the incidence of mesothelioma in asbestos exposed mice or humans.}, journal = {PloS one}, volume = {9}, number = {8}, pages = {e103025}, pmid = {25093718}, issn = {1932-6203}, mesh = {Adult ; Aged ; Animals ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Asbestos/*adverse effects ; Atorvastatin ; Cohort Studies ; Cyclooxygenase 2 Inhibitors/therapeutic use ; Female ; Heptanoic Acids/*therapeutic use ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic use ; Incidence ; Lung Neoplasms/*epidemiology/*etiology ; Male ; Mesothelioma/*epidemiology/*etiology ; Mice ; Mice, Transgenic ; Middle Aged ; Pyrroles/*therapeutic use ; }, abstract = {Mesothelioma is principally caused by asbestos and may be preventable because there is a long latent period between exposure and disease development. The most at-risk are a relatively well-defined population who were exposed as a consequence of their occupations. Although preventative agents investigated so far have not been promising, discovery of such an agent would have a significant benefit world-wide on healthcare costs and personal suffering. Statins are widely used for management of hypercholesterolemia and cardiovascular risk; they can induce apoptosis in mesothelioma cells and epidemiological data has linked their use to a lower incidence of cancer. We hypothesised that statins would inhibit the development of asbestos-induced mesothelioma in mice and humans. An autochthonous murine model of asbestos-induced mesothelioma was used to test this by providing atorvastatin daily in the feed at 100 mg/kg, 200 mg/kg and 400 mg/kg. Continuous administration of atorvastatin did not alter the rate of disease development nor increase the length of time that mice survived. Latency to first symptoms of disease and disease progression were also unaffected. In a parallel study, the relationship between the use of statins and development of mesothelioma was investigated in asbestos-exposed humans. In a cohort of 1,738 asbestos exposed people living or working at a crocidolite mine site in Wittenoom, Western Australia, individuals who reported use of statins did not have a lower incidence of mesothelioma (HR = 1.01; 95% CI = 0.44-2.29, p = 0.99). Some individuals reported use of both statins and non-steroidal anti-inflammatory drugs or COX-2 inhibitors, and these people also did not have an altered risk of mesothelioma development (HR = 1.01; 95% CI = 0.61-1.67, p = 0.97). We conclude that statins do not moderate the rate of development of mesothelioma in either a mouse model or a human cohort exposed to asbestos.}, } @article {pmid25093494, year = {2014}, author = {Farioli, A and Mattioli, S and Curti, S and Violante, FS}, title = {Comment on 'The latency period of mesothelioma among a cohort of British asbestos workers (1978-2005)': the effect of left censoring.}, journal = {British journal of cancer}, volume = {111}, number = {11}, pages = {2197-2198}, pmid = {25093494}, issn = {1532-1827}, mesh = {Asbestos/*adverse effects ; Female ; Humans ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology ; Occupational Exposure/*adverse effects ; }, } @article {pmid25093490, year = {2014}, author = {Frost, G}, title = {Response to comment on 'The latency period of mesothelioma among a cohort of British asbestos workers (1978-2005)'.}, journal = {British journal of cancer}, volume = {111}, number = {11}, pages = {2198-2199}, pmid = {25093490}, issn = {1532-1827}, mesh = {Asbestos/*adverse effects ; Female ; Humans ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology ; Occupational Exposure/*adverse effects ; }, } @article {pmid25078800, year = {2014}, author = {Silvestri, S and Nemo, A}, title = {[Reconstruction of past asbestos exposure of dockers in the Port of Livorno].}, journal = {La Medicina del lavoro}, volume = {105}, number = {3}, pages = {187-196}, pmid = {25078800}, issn = {0025-7818}, mesh = {Asbestos/*adverse effects ; Humans ; Italy ; Occupational Exposure/*adverse effects/statistics & numerical data ; Ships ; Time Factors ; }, abstract = {INTRODUCTION: In the period 1957/1995 more than 200,000 tons of asbestos arrived at the Port of Livorno. This paper attempts to reconstruct the levels of exposure of the dockers during this period, given the absence of any environmental investigations.

METHODS: The estimates were calculated using the quantities unloaded annually, the number of dockers, the duration and frequency of the unloading operations, the type of packaging and the background pollution. The Time Weighted Average annual exposure allows calculation of a range of cumulative exposure for each worker with a known period of employment. The working methods were reconstructed interviewing employees and the levels of pollution used in the calculations were partly obtained from published data.

RESULTS: Significant doses were accumulated by dockers who worked at the port in the 60's and 70's. Non-coincidence of the period with the highest imports with that of highest exposure is worth highlighting. Since 1980 the annual average exposure levels were well below the level required for granting insurance compensation benefits. This suggests caution in the use of lists of beneficiaries for epidemiological purposes since the statistical power would be very low.

CONCLUSIONS: The strongest point of the research is the estimated annual TWA exposure that, regardless of the accuracy of the data, does however allow an epidemiological analysis of the cohort for subgroups with different exposure. The twenty-three cases of mesothelioma already recorded in this cohort were first employed before 1966. This method can be used to estimate exposure in other ports, where basic information is available.}, } @article {pmid25077112, year = {2013}, author = {Del Bianco, A and Demers, PA}, title = {Trends in compensation for deaths from occupational cancer in Canada: a descriptive study.}, journal = {CMAJ open}, volume = {1}, number = {3}, pages = {E91-6}, pmid = {25077112}, issn = {2291-0026}, abstract = {BACKGROUND: Occupational cancer is the leading cause of work-related deaths, yet it is often unrecognized and under reported, and associated claims for compensation go unfiled. We sought to examine trends in deaths from occupational cancer, high-risk industries and exposures, and commonly compensated categories of occupational cancers. In addition, we compared deaths from occupational lung cancer for which compensation had been given with total deaths from lung cancer.

METHODS: We used data from the Association of Workers' Compensation Boards of Canada pertaining to the nature and source of the injury or disease and the industry in which it occurred (by jurisdiction) to describe trends in compensated claims for deaths from occupational cancer in Canada for the period 1997-2010. We used data published by the Canadian Cancer Society in Canadian Cancer Statistics to compare compensated occupational lung cancer deaths with total estimated lung cancer deaths for the period between 2006 and 2010.

RESULTS: Compensated claims for deaths from occupational cancer have increased in recent years and surpassed those for traumatic injuries and disorders in Canada, particularly in Ontario. Between 1997 and 2010, one-half of all compensated deaths from occupational cancer in Canada were from Ontario. High-risk industries for occupational cancer include manufacturing, construction, mining and, more recently, government services. Deaths from lung cancer and mesothelioma comprise most of the compensated claims for deaths from occupational cancer in Ontario and Canada. These diseases are usually the result of asbestos exposure. The burden of other occupational carcinogens is not reflected in claims data.

INTERPRETATION: Although the number of accepted claims for deaths from occupational cancers has increased in recent years, these claims likely only represent a fraction of the true burden of this problem. Increased education of patients, workers at high risk of exposure and health care providers is needed to ensure that people with work-related cancer are identified and file a claim for compensation.}, } @article {pmid25069273, year = {2014}, author = {Varivonchik, DV}, title = {[Epidemiologic situation in Ukraine, concerning malignant mesothelioma prevalence].}, journal = {Meditsina truda i promyshlennaia ekologiia}, volume = {}, number = {1}, pages = {18-22}, pmid = {25069273}, issn = {1026-9428}, mesh = {Female ; Humans ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology ; Mesothelioma, Malignant ; Prevalence ; Ukraine/epidemiology ; }, abstract = {Malignant mesothelioma is an "indicator" tumor for evaluating public exposure to asbestos (mostly amphibolitic). Over 2001-2011 in Ukraine a total of 2645 cases of malignant mesothelioma was registered (annual number is 240.5 +/- 29.0 cases). 1 case of malignant mesothelioma per 457.4 tons of asbestos consumed by industry. Median annual levels of malignant mesothelioma morbidity in Ukraine (world standard): males--0.60; females--0.31 per 100,000 of general population. These levels are lower than worldwide (males--1.11; females--0.30) and Europaen WHO ones (males--1.53; female--0.37). Medians of malignant mesothelioma morbidity age are not different between males and females in Ukraine (males 59.5 +/- 13.2 years; females 62.6 +/- 13.1 years; p > 0.05). Most frequent location of malignant mesothelioma is on pleura (males 95.3%; females 89.8%). Now Ukraine is among the countries with low level (< 0.8 per 100,000 general population) and moderate (19.0-0.1% per year) increase of malignant mesothelioma morbidity in European WHO region. Up to 2025, the prognosis is of increased malignant mesothelioma morbidity in Ukraine to 0.97 [0.70-1.18] per 100,000 general population, and in European WHO region--to 2.68. Over 1992-2011, in Ukraine 3 cases of occupational malignant mesothelioma were diagnosed (2 cases of them were connected with occupational exposure to asbestos dust).}, } @article {pmid25068809, year = {2014}, author = {La Vecchia, C and Boffetta, P}, title = {A critique of a review on the relationship between asbestos exposure and the risk of mesothelioma: reply.}, journal = {European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP)}, volume = {23}, number = {5}, pages = {494-496}, doi = {10.1097/CEJ.0000000000000051}, pmid = {25068809}, issn = {1473-5709}, mesh = {Asbestos/*toxicity ; Carcinogens/*toxicity ; Female ; Humans ; Male ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; Occupational Exposure/*statistics & numerical data ; }, } @article {pmid25068808, year = {2014}, author = {Terracini, B and Mirabelli, D and Magnani, C and Ferrante, D and Barone-Adesi, F and Bertolotti, M}, title = {A critique to a review on the relationship between asbestos exposure and the risk of mesothelioma.}, journal = {European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP)}, volume = {23}, number = {5}, pages = {492-494}, doi = {10.1097/CEJ.0000000000000057}, pmid = {25068808}, issn = {1473-5709}, mesh = {Asbestos/*toxicity ; Carcinogens/*toxicity ; Female ; Humans ; Male ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; Occupational Exposure/*statistics & numerical data ; }, } @article {pmid25063896, year = {2013}, author = {Hernández-Solís, A and Garcia-Hernández, C and Reding-Bernal, A and Cruz-Ortiz, H and Cicero-Sabido, R}, title = {[Malignant mesothelioma risk factors: experience in the General Hospital of Mexico].}, journal = {Cirugia y cirujanos}, volume = {81}, number = {4}, pages = {312-316}, pmid = {25063896}, issn = {2444-054X}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Environmental Exposure ; Female ; Hospitals, General/statistics & numerical data ; Humans ; Lung Neoplasms/diagnostic imaging/*etiology/pathology ; Male ; Mesothelioma/diagnostic imaging/*etiology/pathology ; Mesothelioma, Malignant ; Middle Aged ; Neoplastic Syndromes, Hereditary/epidemiology ; Occupational Diseases/etiology/pathology ; Pleural Neoplasms/diagnostic imaging/*etiology/pathology ; Retrospective Studies ; Risk Factors ; Rural Population/statistics & numerical data ; Smoke/adverse effects ; Smoking/adverse effects/epidemiology ; Nicotiana ; Tomography, X-Ray Computed ; Urban Population/statistics & numerical data ; Wood ; }, abstract = {BACKGROUND: Malignant mesothelioma is a neoplasm of bad prognosis, it is linked with asbestos contact, but there are cases without this antecedent.

OBJECTIVE: To investigate the relationship of asbestos exposition and other factors with malignant mesothelioma.

METHODS: Retrospective analysis of histologic confirmed cases of malignant mesothelioma, neoplasic familiar history, tobacco smoking, exposure to wood smoke and to asbestos, were annotated in a paired case/control study 1: 1-3 with logistic regression model to identify risk factors for OR.

RESULTS: 61 cases of malignant mesothelioma were confirmed by histopathologic study, 41 male and 20 female. Mean age was 56 years ± 13 years; 56 cases (91.8%) correspond to epithelial malignant mesothelioma, three sarcomatous (4.9%) one desmoplastic and one biphasic. One in eight (13.1%) had exposure to asbestos. Model of logistic regression with four variables: history of familiar cancer, tobacco smoking, wood smoke and asbestos exposition, the the last one with an OR= 3.083 and p > 0.05. No other variables found to be a risk factor for malignant mesothelioma.

CONCLUSIONS: Exposure to asbestos is a risk factor for malignant mesothelioma, which is confirmed in this study, however it is important to extend the investigation of other possible causal factors of this disease.}, } @article {pmid25061089, year = {2014}, author = {Ai, J and Stevenson, JP}, title = {Current issues in malignant pleural mesothelioma evaluation and management.}, journal = {The oncologist}, volume = {19}, number = {9}, pages = {975-984}, pmid = {25061089}, issn = {1549-490X}, mesh = {Combined Modality Therapy ; Glutamates/therapeutic use ; Guanine/analogs & derivatives/therapeutic use ; Humans ; Lung Neoplasms/diagnosis/genetics/*pathology/*therapy ; Mesothelioma/diagnosis/genetics/*pathology/*therapy ; Mesothelioma, Malignant ; Pemetrexed ; Pleura/*pathology ; Pneumonectomy ; *Prognosis ; Quality of Life ; Radiotherapy, Adjuvant ; Treatment Outcome ; }, abstract = {Malignant pleural mesothelioma (MPM) is an uncommon disease most often associated with occupational asbestos exposure and is steadily increasing in worldwide incidence. Patients typically present at an older age, with advanced clinical stage and other medical comorbidities, making management quite challenging. Despite great efforts, the prognosis of MPM remains poor, especially at progression after initial treatment. Macroscopic complete resection of MPM can be achieved through extrapleural pneumonectomy (EPP) or extended (ie, radical) pleurectomy (e-P/D) in selected patients and can result in prolonged survival when incorporated into a multimodality approach. Given the morbidity associated with surgical resection of MPM, optimizing identification of appropriate patients is essential. Unfortunately, most patients are not candidates for EPP or e-P/D due to advanced stage, age, and/or medical comorbidity. Pemetrexed and platinum combination chemotherapy has become the cornerstone of therapy for patients with unresectable disease because the combination is associated with improved survival and quality of life in treated patients. However, MPM eventually becomes resistant to initial therapy, and benefit to further lines of therapy has not been substantiated in randomized clinical trials. Translational research has provided exciting insights into tumorigenesis, biomarkers, and immune response in MPM, leading to the development of multiple novel therapeutic agents that are currently in clinical trials. These advances hold the promise of a new era in the treatment of MPM and suggest that this disease will not be left behind in the war on cancer.}, } @article {pmid25053605, year = {2014}, author = {Meisenkothen, C}, title = {The four most pernicious myths in asbestos litigation: Part II: safe thresholds for exposure and Tyndall lighting as junk science.}, journal = {New solutions : a journal of environmental and occupational health policy : NS}, volume = {24}, number = {1}, pages = {27-55}, doi = {10.2190/NS.24.1.b}, pmid = {25053605}, issn = {1541-3772}, mesh = {Air Pollutants, Occupational/*toxicity ; Asbestos, Serpentine/*toxicity ; Culture ; Environmental Exposure/*legislation & jurisprudence ; Expert Testimony ; Humans ; Mesothelioma/*chemically induced ; Occupational Diseases/*chemically induced ; *Threshold Limit Values ; United States ; }, abstract = {Part I of this survey confronted the first two Most Pernicious Myths in Asbestos Litigation: the supposed harmlessness of chrysotile asbestos; and so-called idiopathic mesothelioma. Part II discusses the pernicious notions of safe exposure thresholds for asbestos and the unreliability of Tyndall lighting. Defendants' attempts to preclude plaintiffs' experts from testifying about these generally accepted scientific facts are a disservice to the legal system and to plaintiffs who have been harmed by asbestos. These defense tactics attempt to deny reality and to spin scientific facts in order to keep them from the jurors' eyes and ears. This undermines the legal system and harms the integrity of the scientific enterprise. Defendants' efforts to manufacture "controversy" over previously uncontroversial facts are bald attempts to infect the legal process with junk "doubt science." The role of this type of "doubt science" is being steadily exposed as legitimate researchers resist the degradation of their disciplines and the scientific literature by unprincipled purveyors of this insidious brand of junk science.}, } @article {pmid25053604, year = {2014}, author = {Meisenkothen, C}, title = {The four most pernicious myths in asbestos litigation: Part I: safe chrysotile and idiopathic mesothelioma.}, journal = {New solutions : a journal of environmental and occupational health policy : NS}, volume = {24}, number = {1}, pages = {1-26}, doi = {10.2190/NS.24.1.a}, pmid = {25053604}, issn = {1541-3772}, mesh = {Air Pollutants, Occupational/*toxicity ; Asbestos, Serpentine/*toxicity ; Culture ; Environmental Exposure/*legislation & jurisprudence ; Expert Testimony ; Humans ; Mesothelioma/*chemically induced/*pathology ; Occupational Diseases/*chemically induced ; United States ; }, abstract = {The now well documented phenomenon of "doubt science" has crept into litigation generally, but has had a particularly deleterious effect in asbestos litigation, giving rise to pernicious myths that are told and re-told every day in legal briefs and in court proceedings. Defendants routinely challenge the admissibility of testimony from plaintiffs' expert witnesses when those experts testify about certain key concepts in asbestos medicine and asbestos science. Defendants boldly proclaim plaintiffs' experts' opinions to be "junk science" and seek to have them precluded regardless of how well documented, well researched, well supported and well accepted those opinions are. This has become all too routine in asbestos litigation, where defendants predictably seek to preclude testimony about medical and scientific issues that have been settled for decades and that are not legitimately disputed outside of litigation by the unbiased scientific community of national and international regulatory agencies and scientific organizations.}, } @article {pmid25045719, year = {2014}, author = {Kumagai-Takei, N and Nishimura, Y and Maeda, M and Hayashi, H and Matsuzaki, H and Lee, S and Kishimoto, T and Fukuoka, K and Nakano, T and Otsuki, T}, title = {Functional properties of CD8(+) lymphocytes in patients with pleural plaque and malignant mesothelioma.}, journal = {Journal of immunology research}, volume = {2014}, number = {}, pages = {670140}, pmid = {25045719}, issn = {2314-7156}, mesh = {Asbestos/adverse effects ; Asbestosis/etiology/*immunology/*pathology ; Biomarkers/metabolism ; CD8-Positive T-Lymphocytes/*immunology/metabolism ; Cell Degranulation/immunology ; Cells, Cultured ; Granzymes/metabolism ; Humans ; Immunophenotyping ; Interferon-gamma/biosynthesis ; Leukocytes, Mononuclear/immunology/metabolism ; Lung Neoplasms/etiology/*immunology ; Mesothelioma/etiology/*immunology ; Mesothelioma, Malignant ; Perforin/metabolism ; Pleura/*pathology ; T-Lymphocyte Subsets/immunology/metabolism ; }, abstract = {It is known that asbestos exposure can cause malignant mesothelioma (MM) and that CD8(+) T cells play a critical role in antitumor immunity. We examined the properties of peripheral blood CD8(+) lymphocytes from asbestos-exposed patients with pleural plaque (PL) and MM. The percentage of CD3(+)CD8(+) cells in PBMCs did not differ among the three groups, although the total numbers of PBMCs of the PL and MM groups were lower than those of the healthy volunteers (HV). The percentage of IFN-γ (+) and CD107a(+) cells in PMA/ionomycin-stimulated CD8(+) lymphocytes did not differ among the three groups. Percentages of perforin(+) cells and CD45RA(-) cells in fresh CD8(+) lymphocytes of PL and MM groups were higher than those of HV. Percentages of granzyme B(+) and perforin(+) cells in PMA/ionomycin-stimulated CD8(+) lymphocytes were higher in PL group compared with HV. The MM group showed a decrease of perforin level in CD8(+) lymphocytes after stimulation compared with patients with PL. These results indicate that MM patients have characteristics of impairment in stimulation-induced cytotoxicity of peripheral blood CD8(+) lymphocytes and that PL and MM patients have a common character of functional alteration in those lymphocytes, namely, an increase in memory cells, possibly related to exposure to asbestos.}, } @article {pmid25045139, year = {2014}, author = {Sato, T and Suzuki, Y and Mori, T and Maeda, M and Abe, M and Hino, O and Takahashi, K}, title = {Newly established ELISA for N-ERC/mesothelin improves diagnostic accuracy in patients with suspected pleural mesothelioma.}, journal = {Cancer medicine}, volume = {3}, number = {5}, pages = {1377-1384}, pmid = {25045139}, issn = {2045-7634}, mesh = {Enzyme-Linked Immunosorbent Assay/*methods/standards ; GPI-Linked Proteins/blood/*metabolism ; Humans ; Lung Neoplasms/*diagnosis/*metabolism ; Mesothelin ; Mesothelioma/*diagnosis/*metabolism ; Mesothelioma, Malignant ; Pleural Neoplasms/*diagnosis/*metabolism ; Reproducibility of Results ; }, abstract = {Pleural mesothelioma is an aggressive tumor, commonly caused by exposure to asbestos. The prognosis of mesothelioma remains disappointing despite multimodal treatment. We reported previously that N-ERC/mesothelin could be a useful biomarker for the early diagnosis of pleural mesothelioma and developed an enzyme-linked immunosorbent assay (ELISA) system for its detection. However, the reproducibility of our previous 7-16 ELISA system has been revealed to be unsatisfactory. To measure N-ERC/mesothelin more precisely, we developed a new 7-20 ELISA system. The subjects of this study were patients who were referred to our department with suspected pleural mesothelioma. The current study demonstrated that the newly established 7-20 ELISA system improved the sensitivity and specificity for diagnosing pleural mesothelioma compared with the previous system. Moreover, the 7-20 ELISA system showed better reproducibility and displayed the tendency of both higher sensitivity and higher specificity in plasma than in serum. Particularly for the epithelioid type, the area under the curve (AUC) and the diagnostic accuracy of N-ERC/mesothelin were excellent; the AUC was 0.91, the sensitivity was 0.95, and the specificity was 0.76 in plasma. In conclusion, assessment of N-ERC/mesothelin with our newly established 7-20 ELISA system is clinically useful for the precise diagnosis of pleural mesothelioma.}, } @article {pmid25040312, year = {2015}, author = {Exarchos, GD and Attanoos, RL}, title = {Pseudomesotheliomatous small-cell neuroendocrine carcinoma of the lung with calretinin expression.}, journal = {Histopathology}, volume = {66}, number = {6}, pages = {895-896}, doi = {10.1111/his.12484}, pmid = {25040312}, issn = {1365-2559}, mesh = {Aged ; Asbestos/adverse effects ; Biomarkers, Tumor/analysis ; Calbindin 2/analysis ; Carcinoma, Neuroendocrine/*diagnosis/etiology ; Diagnosis, Differential ; Humans ; Lung Neoplasms/*diagnosis/etiology ; Male ; Mesothelioma/diagnosis ; Occupational Exposure/adverse effects ; Small Cell Lung Carcinoma/*diagnosis/etiology ; }, } @article {pmid25037982, year = {2014}, author = {Creaney, J and Dick, IM and Meniawy, TM and Leong, SL and Leon, JS and Demelker, Y and Segal, A and Musk, AW and Lee, YC and Skates, SJ and Nowak, AK and Robinson, BW}, title = {Comparison of fibulin-3 and mesothelin as markers in malignant mesothelioma.}, journal = {Thorax}, volume = {69}, number = {10}, pages = {895-902}, pmid = {25037982}, issn = {1468-3296}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antigens, Neoplasm ; Biomarkers, Tumor ; Biopsy ; Diagnosis, Differential ; Enzyme-Linked Immunosorbent Assay ; Extracellular Matrix Proteins/*metabolism ; Female ; Follow-Up Studies ; GPI-Linked Proteins/*metabolism ; Humans ; Immunohistochemistry ; Lung Neoplasms/*metabolism/pathology ; Male ; Mesothelin ; Mesothelioma/*metabolism/pathology ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/*metabolism/pathology ; Prognosis ; Prospective Studies ; ROC Curve ; Young Adult ; }, abstract = {BACKGROUND: Pleural malignant mesothelioma (MM) is a deadly tumour predominantly associated with asbestos exposure. A reliable diagnostic and prognostic marker for MM will significantly enhance clinical care and is an area of intense research. Soluble mesothelin is the most studied and an FDA-approved biomarker for MM. A recent report showed promising results using fibulin-3 as a new diagnostic marker. The aim of this study was to compare the utility of fibulin-3 versus mesothelin, singly or in combination.

METHODS: Fibulin-3 and soluble mesothelin were determined by ELISA in the plasma and pleural fluid of 153 patients presenting with a pleural effusion including 82 with MM, 36 with non-MM malignant effusions and 35 with benign effusions. Biomarker concentrations were determined in the plasma of an additional 49 cases with benign asbestos-related disease.

RESULTS: Mesothelin provides better diagnostic accuracy than fibulin-3 for MM whether measured in plasma or pleural effusion: area under the curve (AUC) for plasma was 0.822 (95% CI 0.76 to 0.87) compared with 0.671 (0.61 to 0.73), respectively, and for pleural fluid AUC was 0.815 (0.74 to 0.87) compared with 0.588 (0.51 to 0.67), respectively. Effusion fibulin-3 was an independent significant prognostic factor for survival in MM patients; HR 2.08 (1.14 to 3.82), p=0.017. MM patients with effusion fibulin-3 levels below the median survived significantly longer than those with levels above the median (14.1 vs 7.9 months, p=0.012). Mesothelin and neutrophil to lymphocyte ratio were not significant prognostic markers.

CONCLUSIONS: Soluble mesothelin is a superior diagnostic biomarker for MM compared with fibulin-3, whereas fibulin-3 provides superior prognostic information compared with mesothelin.}, } @article {pmid25034569, year = {2014}, author = {Lacourt, A and Rinaldo, M and Gramond, C and Ducamp, S and Gilg Soit Ilg, A and Goldberg, M and Pairon, JC and Brochard, P}, title = {Co-exposure to refractory ceramic fibres and asbestos and risk of pleural mesothelioma.}, journal = {The European respiratory journal}, volume = {44}, number = {3}, pages = {725-733}, doi = {10.1183/09031936.00079814}, pmid = {25034569}, issn = {1399-3003}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Case-Control Studies ; Ceramics/*adverse effects ; France ; Humans ; Logistic Models ; Male ; Mesothelioma/*chemically induced/etiology ; Middle Aged ; Occupational Diseases/chemically induced/etiology ; Occupational Exposure ; Pleural Neoplasms/*chemically induced/etiology ; Registries ; Risk Factors ; Time Factors ; }, abstract = {The aim of this study was to investigate the hypothesis of an increased risk of pleural mesothelioma due to co-exposure to asbestos and refractory ceramic fibres (RCF) compared to asbestos exposure alone. Males were selected from a French case-control study conducted in 1987-1993 and from the French National Mesothelioma Surveillance Program in 1998-2006. Two population controls were frequency matched to each case by year of birth. Complete job histories were collected and occupational asbestos and RCF exposures were assessed using job exposure matrices. The dose-response relationships for asbestos exposure were estimated from an unconditional logistic regression model in subjects exposed to asbestos only (group 1) and subjects exposed to both asbestos and RCF (group 2). A total of 988 cases and 1125 controls ever-exposed to asbestos were included. A dose-response relationship was observed in both groups but it was stronger in group 2. In comparison with subjects exposed at the minimum value of the cumulative index of exposure, the odds ratio was 2.6 (95% CI 1.9-3.4) for subjects exposed to 75 fibres · mL(-1) · year(-1) in group 1 increasing to 12.4 (95% CI 4.6-33.7) in group 2. Our results suggest that the pleural carcinogenic effect of occupational asbestos exposure may be modified by additional exposure to RCF.}, } @article {pmid25026285, year = {2014}, author = {Ortolan, E and Giacomino, A and Martinetto, F and Morone, S and Lo Buono, N and Ferrero, E and Scagliotti, G and Novello, S and Orecchia, S and Ruffini, E and Rapa, I and Righi, L and Volante, M and Funaro, A}, title = {CD157 enhances malignant pleural mesothelioma aggressiveness and predicts poor clinical outcome.}, journal = {Oncotarget}, volume = {5}, number = {15}, pages = {6191-6205}, pmid = {25026285}, issn = {1949-2553}, mesh = {ADP-ribosyl Cyclase/analysis/*biosynthesis ; Antigens, CD/analysis/*biosynthesis ; Biomarkers, Tumor/analysis/*biosynthesis ; Cell Line, Tumor ; Cell Proliferation/physiology ; Female ; GPI-Linked Proteins/analysis/biosynthesis ; Humans ; Lung Neoplasms/diagnosis/*metabolism/pathology ; Male ; Mesothelioma/diagnosis/*metabolism/pathology ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/diagnosis/*metabolism/pathology ; Prognosis ; Signal Transduction ; Survival Analysis ; Treatment Outcome ; }, abstract = {Malignant mesothelioma is a deadly tumor whose diagnosis and treatment remain very challenging. There is an urgent need to advance our understanding of mesothelioma biology and to identify new molecular markers for improving management of patients. CD157 is a membrane glycoprotein linked to ovarian cancer progression and mesenchymal differentiation. The common embryonic origin of ovarian epithelial cells and mesothelial cells and the evident similarities between ovarian and mesothelial cancer prompted us to investigate the biological role and clinical significance of CD157 in malignant pleural mesothelioma (MPM). CD157 mRNA and protein were detected in four of nine MPM cell lines of diverse histotype and in 85.2% of MPM surgical tissue samples (32/37 epithelioid; 37/44 biphasic). CD157 expression correlated with clinical aggressiveness in biphasic MPM. Indeed, high CD157 was a negative prognostic factor and an independent predictor of poor survival for patients with biphasic MPM by multivariate survival analysis (HR = 2.433, 95% CI 1.120-5.284; p = 0.025). In mesothelioma cell lines, CD157 gain (in CD157-negative cells) or knockdown (in CD157-positive cells) affected cell growth, migration, invasion and tumorigenicity, most notably in biphasic MPM cell lines. In these cells, CD157 expression was associated with increased activation of the mTOR signaling pathway, resulting in decreased platinum sensitivity. Moreover, a trend towards reduced survival was observed in patients with biphasic MPM receiving postoperative platinum-based chemotherapy. These findings indicate that CD157 is implicated in multiple aspects of MPM progression and suggest that CD157 expression could be used to stratify patients into different prognostic groups or to select patients that might benefit from particular chemotherapeutic approach.}, } @article {pmid25013421, year = {2014}, author = {Erdogan, S and Acikalin, A and Zeren, H and Gonlusen, G and Zorludemir, S and Izol, V}, title = {Well-differentiated papillary mesothelioma of the tunica vaginalis: a case study and review of the literature.}, journal = {Korean journal of pathology}, volume = {48}, number = {3}, pages = {225-228}, pmid = {25013421}, issn = {1738-1843}, abstract = {Well-differentiated papillary mesothelioma is an uncommon tumor of the testes that usually presents as a hydrocele. Here, we present the case of one patient who did not have a history of asbestos exposure. The tumor was localized in the tunica vaginalis and was composed of three pedunculated masses macroscopically. Microscopically, branching papillary structures with focal coagulative necrosis were present. In addition to immunohistochemistry, simian virus 40 DNA was also tested by polymerase chain reaction. This report presents one case of this rare entity, its clinical and macroscopic features, and follow-up results.}, } @article {pmid25010395, year = {2014}, author = {Kobayashi, S and Waragai, T and Sano, H and Mochizuki, K and Akaihata, M and Ohara, Y and Hosoya, M and Kikuta, A}, title = {Malignant peritoneal mesothelioma in a child: chemotherapy with gemcitabine and platinum was effective for the disease unresponsive to other treatments.}, journal = {Anti-cancer drugs}, volume = {25}, number = {9}, pages = {1102-1105}, doi = {10.1097/CAD.0000000000000143}, pmid = {25010395}, issn = {1473-5741}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Ascites/drug therapy ; Child ; Cisplatin/administration & dosage ; Deoxycytidine/administration & dosage/analogs & derivatives ; Drug Resistance, Neoplasm ; Glutamates/therapeutic use ; Guanine/analogs & derivatives/therapeutic use ; Humans ; Lung Neoplasms/*drug therapy ; Male ; Mesothelioma/*drug therapy ; Mesothelioma, Malignant ; Pemetrexed ; Peritoneal Neoplasms/*drug therapy ; Gemcitabine ; }, abstract = {Malignant peritoneal mesothelioma in children is a very rare disease and has a poor prognosis. Unlike malignant mesothelioma in adults, there is no clear causal association between this very rare malignancy in children and asbestos exposure. We report a case of peritoneal mesothelioma in an 11-year-old boy who presented with ascites. He was diagnosed with malignant mesothelioma on the basis of histopathological findings. His disease showed resistance to pemetrexed, but was treated successfully with platinum-based therapy with gemcitabine. He has achieved long-term survival in partial remission with stable disease.}, } @article {pmid25006323, year = {2014}, author = {Kim, I and Kim, EA and Kim, JY}, title = {Compensation for occupational cancer.}, journal = {Journal of Korean medical science}, volume = {29 Suppl}, number = {Suppl}, pages = {S40-6}, pmid = {25006323}, issn = {1598-6357}, mesh = {Asbestos/toxicity ; Benzene/toxicity ; Carcinogens/toxicity ; Female ; Humans ; Insurance, Health/*economics ; Middle Aged ; Neoplasms/chemically induced/*economics ; Occupational Diseases/*economics/mortality ; Occupational Exposure/*adverse effects ; Republic of Korea ; Workers' Compensation/*economics/legislation & jurisprudence/standards ; }, abstract = {The legal scope and criteria for occupational cancer in Korea was out of date. The aim of this study was to review the current criteria for occupational cancer and amend the existent criteria on the basis of recent scientific evidence. The scientific evidence and the legal list of occupational cancer were analyzed to identify the causes of occupational cancer on a global scale. The relationship between compensated occupational cancer cases and carcinogen exposure in Korea was examined. The factors associated with specific causes and target cancers were determined to produce additional criteria. Five-hundred and nineteen cases of 2,468 were awarded compensation for occupational cancer including lung, malignant mesothelioma, lymphohematopoietic, and liver cancers from January 2000 to October 2012. Between 1996 and 2005, benzene accounted for 84.4% of cases, and between 1999 and 2005, asbestos was associated with 62.3% of cases. Fourteen novel causative agents and 12 additional target cancers were identified and the final guidelines were amended to include 23 causative agents and 21 target cancers. This amendment of the criteria for occupational cancer represents the widest change in Korean history and is expected to improve the understanding of occupational cancer by providing an up-to-date and accurate reference guide.}, } @article {pmid24999848, year = {2014}, author = {Van den Borre, L and Deboosere, P}, title = {Asbestos in Belgium: an underestimated health risk. The evolution of mesothelioma mortality rates (1969-2009).}, journal = {International journal of occupational and environmental health}, volume = {20}, number = {2}, pages = {134-140}, pmid = {24999848}, issn = {1077-3525}, mesh = {Belgium/epidemiology ; Female ; Global Health ; Humans ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; Occupational Exposure/*adverse effects/*statistics & numerical data ; Sex Distribution ; }, abstract = {BACKGROUND: Although Belgium was once a major international manufacturer of asbestos products, asbestos-related diseases in the country have remained scarcely researched.

OBJECTIVES: The aim of this study is to provide a descriptive analysis of Belgian mesothelioma mortality rates in order to improve the understanding of asbestos health hazards from an international perspective.

METHODS: Temporal and geographical analyses were performed on cause-specific mortality data (1969-2009) using quantitative demographic measures. Results were compared to recent findings on global mesothelioma deaths.

RESULTS: Belgium has one of the highest mesothelioma mortality rates in the world, following the UK, Australia, and Italy. With a progressive increase of male mesothelioma deaths in the mid-1980s, large differences in mortality rates between sexes are apparent. Mesothelioma deaths are primarily concentrated in geographic areas with proximity to former asbestos industries.

CONCLUSIONS: Asbestos mortality in Belgium has been underestimated for decades. Our findings suggest that the location of asbestos industries is correlated with rates of mesothelioma, underlining the need to avert future asbestos exposure by thorough screening of potential contaminated sites and by pursuing a global ban on asbestos.}, } @article {pmid24999846, year = {2014}, author = {Egilman, D and Bird, T and Lee, C}, title = {Dust diseases and the legacy of corporate manipulation of science and law.}, journal = {International journal of occupational and environmental health}, volume = {20}, number = {2}, pages = {115-125}, pmid = {24999846}, issn = {1077-3525}, mesh = {Air Pollutants, Occupational/*toxicity ; Asbestosis/etiology ; *Dust ; Humans ; Industry/*legislation & jurisprudence ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Occupational Exposure/*legislation & jurisprudence ; Occupational Health ; *Politics ; Silicosis/etiology ; United States/epidemiology ; United States Occupational Safety and Health Administration ; }, abstract = {BACKGROUND: The dust diseases silicosis and asbestosis were the first occupational diseases to have widespread impact on workers. Knowledge that asbestos and silica were hazardous to health became public several decades after the industry knew of the health concerns. This delay was largely influenced by the interests of Metropolitan Life Insurance Company (MetLife) and other asbestos mining and product manufacturing companies.

OBJECTIVES: To understand the ongoing corporate influence on the science and politics of asbestos and silica exposure, including litigation defense strategies related to historical manipulation of science.

METHODS: We examined previously secret corporate documents, depositions and trial testimony produced in litigation; as well as published literature.

RESULTS: Our analysis indicates that companies that used and produced asbestos have continued and intensified their efforts to alter the asbestos-cancer literature and utilize dust-exposure standards to avoid liability and regulation. Organizations of asbestos product manufacturers delayed the reduction of permissible asbestos exposures by covering up the link between asbestos and cancer. Once the decline of the asbestos industry in the US became inevitable, the companies and their lawyers designed the state of the art (SOA) defense to protect themselves in litigation and to maintain sales to developing countries.

CONCLUSIONS: Asbestos product companies would like the public to believe that there was a legitimate debate surrounding the dangers of asbestos during the twentieth century, particularly regarding the link to cancer, which delayed adequate regulation. The asbestos-cancer link was not a legitimate contestation of science; rather the companies directly manipulated the scientific literature. There is evidence that industry manipulation of scientific literature remains a continuing problem today, resulting in inadequate regulation and compensation and perpetuating otherwise preventable worker and consumer injuries and deaths.}, } @article {pmid24986501, year = {2014}, author = {Pirastu, R and Ricci, P and Comba, P and Bianchi, F and Biggeri, A and Conti, S and Fazzo, L and Forastiere, F and Iavarone, I and Martuzzi, M and Musmeci, L and Pasetto, R and Zona, A and Crocetti, E}, title = {[SENTIERI Project: discussion and conclusions].}, journal = {Epidemiologia e prevenzione}, volume = {38}, number = {2 Suppl 1}, pages = {125-133}, pmid = {24986501}, issn = {1120-9763}, mesh = {Asbestos/adverse effects ; Breast Neoplasms/epidemiology/etiology ; Carcinogens/toxicity ; Environmental Exposure/*adverse effects ; Female ; Hazardous Substances/adverse effects ; Humans ; Incidence ; Italy/epidemiology ; Lung Neoplasms/epidemiology/etiology ; Lymphoma, Non-Hodgkin/epidemiology/etiology ; Melanoma/epidemiology/etiology ; Neoplasms/*epidemiology/*etiology/mortality/prevention & control ; Patient Discharge/*statistics & numerical data ; Public Health ; Respiratory Tract Diseases/epidemiology/etiology ; Risk Factors ; Sex Distribution ; Skin Neoplasms/epidemiology/etiology ; Survival Rate ; Thyroid Neoplasms/epidemiology/etiology ; Time Factors ; World Health Organization ; }, abstract = {The SENTIERI Project represents the first comprehensive analysis of the health impact of residence in National Priority Contaminated Sites (NPCSs). For the first time, it considers three distinct health outcomes: mortality (2003-2010), cancer incidence (1996- 2005) and hospital discharges (2005-2010). The Report includes a commentary explaining methodology and approach, as well as remarks on the causal association between environmental exposures and investigated health outcomes based on the a priori assessments of the epidemiological evidence; the main implications for public health and scientific research priorities are also presented. The approach put forward by SENTIERI was among those sanctioned by the World Health Organization to conduct an initial description of the health status of residents of contaminated sites. Results relating to individual diseases that can be traced back to a single agent, such as asbestiform fibres, can be easily analysed. The Biancavilla NPCS (where the fluoro-edenite asbestiform fibre was found) displays excesses of pleural mesothelioma and its proxy, malignant pleural tumours, as does Priolo, where asbestos coexists with other pollutants. Increased risk was also recorded in NPCSs adjacent to the coast hosting harbour areas (such as Trieste, Taranto and Venice) or comprising industrial areas specialising in the production of chemicals (Laguna di Grado e Marano, Priolo and Venezia) and steel (Taranto, Terni, Trieste). Increases of pathologies, such as cancer and respiratory diseases, connected to more than one agent, in industrial sites with multiple and diverse sources of exposures, prove harder to interpret. There are also more complex cases in which results do not appear consistent in the three databases or by gender (such as lung cancer in Venice, where mortality and hospital discharges have only increased among women). In order to adequately examine these we must consider factors such as the appropriateness of the health outcome showing the increase, considering latency and the length of the observation period. Of further interest are results relating to diseases of the urinary tract such as kidney failure in the NPCSs of Basso bacino del fiume Chienti, Taranto, Milazzo and Priolo. Overall, the results discussed above are consistent with the previous findings pertaining to mortality for 1995-2002. The present analysis also introduces a new element - the study of cancer incidence and hospital discharges - which can tell us a great deal about diseases with high survival rates or non lethal ones. The first is the case of thyroid cancer, which presents increases in both databases and for both genders in a number of NPCSs (Brescia-Caffaro, Laghi di Mantova, Milazzo, Sassuolo- Scandiano and Taranto). The study of cancer incidence and hospital discharges also revealed cancer excesses for melanoma, breast cancer and non Hodgkin lymphoma in Brescia-Caffaro NPCS where PCBs (Polychlorinated biphenyl) are the site's main pollutant. PCBs, according to the 2013 evaluation of the International Agency for Research on Cancer, are ascertained human carcinogens for melanoma and probable carcinogens for breast cancer and non-Hodgkin lymphoma. The results pertaining to cancer incidence in the 17 NPCSs can also be presented using rankings by area or disease analyzed by a multivariate hierarchical Bayesian model. These rankings reveal an overlapping of credibility intervals, such that it is not possible to speak of a limited number of cancer sites or of certain NPCSs as being particularly affected. Every NPCS, therefore, must be considered individually and ordering them by ranking of cancer incidence wouldn't be appropriate. Data collected concerning some of the NPCSs in the context of the SENTIERI Project is so conclusive that remediation measures can immediately be put in place. This is the case in the Biancavilla and Brescia-Caffaro NPCSs. A similar conclusion can be drawn for complex locations such as Taranto, where, based on the results of SENTIERI Projects and the whole available information, we can safely conclude that exposure to environmental agents played an important role, allowing us to set in place 'Integrated evaluation of environmental and health impact procedures'. SENTIERI approach does not allow definitive causal assessments. However, as stated above, these results do provide a topic for further study without getting in the way of initiatives promoting urgent environmental remediation.}, } @article {pmid24973234, year = {2015}, author = {Samuels, A}, title = {Mesothelioma and the law.}, journal = {The Medico-legal journal}, volume = {83}, number = {1}, pages = {26-28}, doi = {10.1177/0025817214528433}, pmid = {24973234}, issn = {2042-1834}, mesh = {Asbestos/*adverse effects ; Humans ; *Jurisprudence ; *Malpractice ; Mesothelioma/*etiology/*pathology ; Occupational Diseases/etiology ; }, } @article {pmid24968911, year = {2014}, author = {Ballan, G and Del Brocco, A and Loizzo, S and Fabbri, A and Maroccia, Z and Fiorentini, C and Travaglione, S}, title = {Mode of action of fibrous amphiboles: the case of Biancavilla (Sicily, Italy).}, journal = {Annali dell'Istituto superiore di sanita}, volume = {50}, number = {2}, pages = {133-138}, doi = {10.4415/ANN_14_02_05}, pmid = {24968911}, issn = {2384-8553}, mesh = {Animals ; Asbestos, Amphibole/*toxicity ; Cell Line, Tumor ; *Endemic Diseases ; Humans ; Inhalation Exposure/adverse effects ; Mesothelioma/*epidemiology/etiology/veterinary ; Neoplasms/epidemiology/etiology/veterinary ; Particle Size ; Sicily/epidemiology ; }, abstract = {BACKGROUND: The inhalation of fibrous amphiboles can result in pulmonary fibrosis, lung cancer and mesothelioma. Although these fibres have the same disease-causing potential, their different morphologies and chemical composition can determine different biological activities. An unusual cluster of mesothelioma was evidenced in Biancavilla (Sicily) where no inhabitant had been significantly exposed to asbestos.

OBJECTIVE: We herein discuss the mechanism of action of amphiboles, focusing on the fibres identified in the study area.

RESULTS: Human lung carcinoma cells have been exposed to two different materials: prismatic fluoro-edenite and fibres with fluoro-edenitic composition. Only in the second case, they exhibit features typical of transformed cells, such as multinucleation, prosurvival activity and pro-inflammatory cytokine release. Accordingly, in vivo studies demonstrated that the fibrous sample only could induce a mesotheliomatogenic effect.

CONCLUSIONS: Fibres with fluoro-edenitic composition behave similarly to the asbestos crocidolite, whose connection with inflammation and lung cancer is well established.}, } @article {pmid24968910, year = {2014}, author = {Conti, S and Minelli, G and Manno, V and Iavarone, I and Comba, P and Scondotto, S and Cernigliaro, A}, title = {Health impact of the exposure to fibres with fluoro-edenitic composition on the residents in Biancavilla (Sicily, Italy): mortality and hospitalization from current data.}, journal = {Annali dell'Istituto superiore di sanita}, volume = {50}, number = {2}, pages = {127-132}, doi = {10.4415/ANN_14_02_04}, pmid = {24968910}, issn = {2384-8553}, mesh = {Asbestos, Amphibole/*adverse effects ; Environmental Exposure/*adverse effects ; Environmental Pollution/*adverse effects ; Hospitalization/statistics & numerical data ; Humans ; Mesothelioma/etiology/*mortality ; Pneumoconiosis/etiology/*mortality ; Respiratory Tract Neoplasms/etiology/mortality ; Sicily/epidemiology ; }, abstract = {INTRODUCTION: The objective of this chapter is to study the health impact of the exposure to fibres with fluoro-edenitic composition on the residents in Biancavilla (Sicily, Italy), in terms of mortality and hospitalization. The diseases which international scientific literature indicates as associated with asbestos exposure were taken into consideration: mesothelioma of pleura, peritoneum, pericardium and tunica vaginalis testis, malignant neoplasm of larynx, malignant neoplasm of trachea, bronchus and lung, malignant neoplasm of ovary, pneumoconiosis; moreover, in order to describe the health profile of the study population, large groups of diseases were taken into consideration.

MATERIAL AND METHODS: Current data (available in the Data Bases of the Unit of Statistics of ISS) regarding mortality and hospitalization were analyzed. Standardized Mortality Ratios, Standardized Hospitalization Ratios and Age-standardized Death Rates were calculated. The demographic background of the population residing in Biancavilla was also outlined.

CONCLUSIONS: Our findings support the etiologic role of fibres with fluoro-edenitic composition in the occurrence of the above mentioned diseases, already observed in other studies.}, } @article {pmid24968908, year = {2014}, author = {Bruno, C and Tumino, R and Fazzo, L and Cascone, G and Cernigliaro, A and De Santis, M and Giurdanella, MC and Nicita, C and Rollo, PC and Scondotto, S and Spata, E and Zona, A and Comba, P}, title = {Incidence of pleural mesothelioma in a community exposed to fibres with fluoro-edenitic composition in Biancavilla (Sicily, Italy).}, journal = {Annali dell'Istituto superiore di sanita}, volume = {50}, number = {2}, pages = {111-118}, doi = {10.4415/ANN_14_02_02}, pmid = {24968908}, issn = {2384-8553}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos, Amphibole/*adverse effects ; Environmental Exposure/*adverse effects ; Female ; Humans ; Incidence ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Pleural Neoplasms/*epidemiology ; Public Health Surveillance ; Sicily/epidemiology ; Soil/chemistry ; Soil Pollutants/adverse effects ; }, abstract = {INTRODUCTION: Amphibolic fibres with fluoro-edenitic composition characterize Biancavilla soil, including the major quarry from which building materials have been extensively extracted. These fibres induce mesothelioma in experimental animals and their in vitro biological action is similar to that of crocidolite.

MATERIALS AND METHODS: Malignant mesothelioma case series and incidence were examined to evaluate the disease burden on Biancavilla inhabitants.

RESULTS: The incidence of pleural mesothelioma in Biancavilla is steadily higher than in the Sicilian Region, risk estimates are more elevated in women than in men, the most affected age class is constituted by subjects aged less than 50.

DISCUSSION AND CONCLUSIONS: Environmental exposure to fibres with fluoro-edenitic composition appears to be causally related to the elevated mesothelioma occurrence in Biancavilla. In this frame, environmental clean-up is the main goal to be pursued in public health terms. A contribution of scientific research to public health decision making with respect to priority setting for environmental clean-up can derive from some further selected epidemiological investigations.}, } @article {pmid24966347, year = {2014}, author = {Marek, LA and Hinz, TK and von Mässenhausen, A and Olszewski, KA and Kleczko, EK and Boehm, D and Weiser-Evans, MC and Nemenoff, RA and Hoffmann, H and Warth, A and Gozgit, JM and Perner, S and Heasley, LE}, title = {Nonamplified FGFR1 is a growth driver in malignant pleural mesothelioma.}, journal = {Molecular cancer research : MCR}, volume = {12}, number = {10}, pages = {1460-1469}, pmid = {24966347}, issn = {1557-3125}, support = {P50 CA058187/CA/NCI NIH HHS/United States ; P30 CA046934/CA/NCI NIH HHS/United States ; R01 CA108610/CA/NCI NIH HHS/United States ; CA127105/CA/NCI NIH HHS/United States ; UL1 TR001082/TR/NCATS NIH HHS/United States ; R01 CA162226/CA/NCI NIH HHS/United States ; R01 CA127105/CA/NCI NIH HHS/United States ; P50 CA58187/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Autocrine Communication/drug effects/genetics ; Cell Line, Tumor ; Cell Proliferation ; Clone Cells ; Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors/metabolism ; Female ; Fibroblast Growth Factor 2/metabolism ; *Gene Amplification ; Humans ; Imidazoles/pharmacology ; Lung Neoplasms/*genetics/*pathology ; Mesothelioma/*genetics/*pathology ; Mesothelioma, Malignant ; Mice, Nude ; Pleural Neoplasms/*genetics/*pathology ; Pyridazines/pharmacology ; RNA Interference ; Receptor, Fibroblast Growth Factor, Type 1/*genetics ; Signal Transduction ; }, abstract = {UNLABELLED: Malignant pleural mesothelioma (MPM) is associated with asbestos exposure and is a cancer that has not been significantly affected by small molecule-based targeted therapeutics. Previously, we demonstrated the existence of functional subsets of lung cancer and head and neck squamous cell carcinoma (HNSCC) cell lines in which fibroblast growth factor receptor (FGFR) autocrine signaling functions as a nonmutated growth pathway. In a panel of pleural mesothelioma cell lines, FGFR1 and FGF2 were coexpressed in three of seven cell lines and were significantly associated with sensitivity to the FGFR-active tyrosine kinase inhibitor (TKI), ponatinib, both in vitro and in vivo using orthotopically propagated xenografts. Furthermore, RNAi-mediated silencing confirmed the requirement for FGFR1 in specific mesothelioma cells and sensitivity to the FGF ligand trap, FP-1039, validated the requirement for autocrine FGFs. None of the FGFR1-dependent mesothelioma cells exhibited increased FGFR1 gene copy number, based on a FISH assay, indicating that increased FGFR1 transcript and protein expression were not mediated by gene amplification. Elevated FGFR1 mRNA was detected in a subset of primary MPM clinical specimens and like MPM cells; none harbored increased FGFR1 gene copy number. These results indicate that autocrine signaling through FGFR1 represents a targetable therapeutic pathway in MPM and that biomarkers distinct from increased FGFR1 gene copy number such as FGFR1 mRNA would be required to identify patients with MPM bearing tumors driven by FGFR1 activity.

IMPLICATIONS: FGFR1 is a viable therapeutic target in a subset of MPMs, but FGFR TKI-responsive tumors will need to be selected by a biomarker distinct from increased FGFR1 gene copy number, possibly FGFR1 mRNA or protein levels.}, } @article {pmid24958746, year = {2015}, author = {Blackshear, PE and Pandiri, AR and Nagai, H and Bhusari, S and Hong, HH and Ton, TV and Clayton, NP and Wyde, M and Shockley, KR and Peddada, SD and Gerrish, KE and Sills, RC and Hoenerhoff, MJ}, title = {Gene expression of mesothelioma in vinylidene chloride-exposed F344/N rats reveal immune dysfunction, tissue damage, and inflammation pathways.}, journal = {Toxicologic pathology}, volume = {43}, number = {2}, pages = {171-185}, pmid = {24958746}, issn = {1533-1601}, support = {Z99 ES999999//Intramural NIH HHS/United States ; }, mesh = {Animals ; Cell Line, Tumor ; DNA Damage ; Dichloroethylenes/*toxicity ; Female ; Gene Expression Regulation, Neoplastic/*drug effects ; Genes, cdc/drug effects ; Immune System Diseases/*chemically induced/immunology ; Inflammation/*chemically induced/physiopathology ; Lung Neoplasms/*chemically induced/*genetics ; Male ; Mesothelioma/*chemically induced/*genetics ; Mesothelioma, Malignant ; Microarray Analysis ; Peritoneal Neoplasms/chemically induced/pathology ; RNA, Neoplasm/biosynthesis ; Rats ; Rats, Inbred F344 ; Signal Transduction/drug effects ; Testicular Neoplasms/chemically induced/pathology ; }, abstract = {A majority (∼80%) of human malignant mesotheliomas are asbestos-related. However, non-asbestos risk factors (radiation, chemicals, and genetic factors) account for up to 30% of cases. A recent 2-year National Toxicology Program carcinogenicity bioassay showed that male F344/N rats exposed to the industrial toxicant vinylidene chloride (VDC) resulted in a marked increase in malignant mesothelioma. Global gene expression profiles of these tumors were compared to spontaneous mesotheliomas and the F344/N rat mesothelial cell line (Fred-PE) in order to characterize the molecular features and chemical-specific profiles of mesothelioma in VDC-exposed rats. As expected, mesotheliomas from control and VDC-exposed rats shared pathways associated with tumorigenesis, including cellular and tissue development, organismal injury, embryonic development, inflammatory response, cell cycle regulation, and cellular growth and proliferation, while mesotheliomas from VDC-exposed rats alone showed overrepresentation of pathways associated with pro-inflammatory pathways and immune dysfunction such as the nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway, interleukin (IL)-8 and IL-12 signaling, interleukin responses, Fc receptor signaling, and natural killer and dendritic cells signaling, as well as overrepresentation of DNA damage and repair. These data suggest that a chronic, pro-inflammatory environment associated with VDC exposure may exacerbate disturbances in oncogene, growth factor, and cell cycle regulation, resulting in an increased incidence of mesothelioma.}, } @article {pmid24940987, year = {2014}, author = {Sayan, M and Shukla, A and MacPherson, MB and Macura, SL and Hillegass, JM and Perkins, TN and Thompson, JK and Beuschel, SL and Miller, JM and Mossman, BT}, title = {Extracellular signal-regulated kinase 5 and cyclic AMP response element binding protein are novel pathways inhibited by vandetanib (ZD6474) and doxorubicin in mesotheliomas.}, journal = {American journal of respiratory cell and molecular biology}, volume = {51}, number = {5}, pages = {595-603}, pmid = {24940987}, issn = {1535-4989}, support = {R01 ES021110/ES/NIEHS NIH HHS/United States ; T32 ES007122/ES/NIEHS NIH HHS/United States ; }, mesh = {Antibiotics, Antineoplastic/pharmacology/toxicity ; Cell Line, Tumor ; Cell Survival/drug effects/physiology ; Cyclic AMP Response Element-Binding Protein/genetics/*metabolism ; Doxorubicin/*pharmacology/toxicity ; Drug Synergism ; Humans ; MAP Kinase Signaling System/drug effects/*physiology ; Mesothelioma/*drug therapy/metabolism ; Mitogen-Activated Protein Kinase 7/antagonists & inhibitors/genetics/*metabolism ; Neoplasms, Connective Tissue/drug therapy/metabolism ; Phosphorylation/drug effects/physiology ; Piperidines/*pharmacology/toxicity ; Quinazolines/*pharmacology/toxicity ; RNA, Small Interfering/genetics ; Sarcoma/drug therapy/metabolism ; }, abstract = {Malignant mesothelioma (MM), lung cancers, and asbestosis are hyperproliferative diseases associated with exposures to asbestos. All have a poor prognosis; thus, the need to develop novel and effective therapies is urgent. Vandetanib (Van) (ZD6474, ZACTIMA) is a tyrosine kinase inhibitor that has shown equivocal results in clinical trials for advanced non-small cell lung cancer. However, tyrosine kinase inhibitors alone have shown no significant clinical activity in phase II trials of patients with unresectable MM. Using epithelioid (HMESO) and sarcomatoid (H2373) human MM lines, the efficacy of tumor cell killing and signaling pathways modulated by Van with and without doxorubicin (Dox) was examined. Van alone reduced total cell numbers in HMESO MM and synergistically increased the toxicity of Dox in HMESO and H2373 cells. Most importantly, we identified two novel cell survival/resistance pathways, ERK5 and cyclic AMP response element binding protein (CREB), that were inhibited by Van and Dox. After silencing of either ERK5 or CREB, significant decreases in cell numbers in the Dox-resistant sarcomatoid H2373 line were observed. Results suggest that a plethora of cell signaling pathways associated with cell survival are induced by Dox but inhibited by the addition of Van in MM. Data from our study support the combined efficacy of Van and Dox as a novel approach in the treatment of MM that is further enhanced by blocking ERK5 or CREB signaling cascades.}, } @article {pmid24928783, year = {2014}, author = {Xu, J and Kadariya, Y and Cheung, M and Pei, J and Talarchek, J and Sementino, E and Tan, Y and Menges, CW and Cai, KQ and Litwin, S and Peng, H and Karar, J and Rauscher, FJ and Testa, JR}, title = {Germline mutation of Bap1 accelerates development of asbestos-induced malignant mesothelioma.}, journal = {Cancer research}, volume = {74}, number = {16}, pages = {4388-4397}, pmid = {24928783}, issn = {1538-7445}, support = {P30 CA010815/CA/NCI NIH HHS/United States ; R01 CA175691/CA/NCI NIH HHS/United States ; P30 ES013508/ES/NIEHS NIH HHS/United States ; P30 CA006927/CA/NCI NIH HHS/United States ; CA-06927/CA/NCI NIH HHS/United States ; CA175691/CA/NCI NIH HHS/United States ; R01 CA163761/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Asbestos/*toxicity ; Disease Models, Animal ; Epigenomics ; Female ; Genetic Predisposition to Disease ; Genotype ; *Germ-Line Mutation ; Lung Neoplasms/*etiology/*genetics/metabolism ; Mesothelioma/*etiology/*genetics/metabolism ; Mesothelioma, Malignant ; Mice ; Mice, Knockout ; Tumor Suppressor Proteins/*genetics/metabolism ; Ubiquitin Thiolesterase/*genetics/metabolism ; }, abstract = {Malignant mesotheliomas are highly aggressive tumors usually caused by exposure to asbestos. Germline-inactivating mutations of BAP1 predispose to mesothelioma and certain other cancers. However, why mesothelioma is the predominate malignancy in some BAP1 families and not others, and whether exposure to asbestos is required for development of mesothelioma in BAP1 mutation carriers are not known. To address these questions experimentally, we generated a Bap1(+/-) knockout mouse model to assess its susceptibility to mesothelioma upon chronic exposure to asbestos. Bap1(+/-) mice exhibited a significantly higher incidence of asbestos-induced mesothelioma than wild-type (WT) littermates (73% vs. 32%, respectively). Furthermore, mesotheliomas arose at an accelerated rate in Bap1(+/-) mice than in WT animals (median survival, 43 weeks vs. 55 weeks after initial exposure, respectively) and showed increased invasiveness and proliferation. No spontaneous mesotheliomas were seen in unexposed Bap1(+/-) mice followed for up to 87 weeks of age. Mesothelioma cells from Bap1(+/-) mice showed biallelic inactivation of Bap1, consistent with its proposed role as a recessive cancer susceptibility gene. Unlike in WT mice, mesotheliomas from Bap1(+/-) mice did not require homozygous loss of Cdkn2a. However, normal mesothelial cells and mesothelioma cells from Bap1(+/-) mice showed downregulation of Rb through a p16(Ink4a)-independent mechanism, suggesting that predisposition of Bap1(+/-) mice to mesothelioma may be facilitated, in part, by cooperation between Bap1 and Rb. Drawing parallels to human disease, these unbiased genetic findings indicate that BAP1 mutation carriers are predisposed to the tumorigenic effects of asbestos and suggest that high penetrance of mesothelioma requires such environmental exposure.}, } @article {pmid24928677, year = {2014}, author = {Taioli, E and Wolf, AS and Camacho-Rivera, M and Flores, RM}, title = {Women with malignant pleural mesothelioma have a threefold better survival rate than men.}, journal = {The Annals of thoracic surgery}, volume = {98}, number = {3}, pages = {1020-1024}, doi = {10.1016/j.athoracsur.2014.04.040}, pmid = {24928677}, issn = {1552-6259}, support = {5R01TS000099-05/TS/ATSDR CDC HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/*mortality ; Sex Factors ; Survival Rate ; Young Adult ; }, abstract = {BACKGROUND: Many studies have reported that women with malignant pleural mesothelioma (MPM) experience longer survival compared with men, whereas others have not. To date, no large population-based studies have evaluated MPM outcome and its determinants in female patients.

METHODS: All pathologically confirmed cases of MPM in the Surveillance, Epidemiology and End Results database from 1973 to 2009 were evaluated. Age, year of diagnosis, race, stage, cancer-directed surgery, radiation, and vital status were analyzed according to gender. Cox proportional hazard models were derived to assess the association between prognostic factors and survival.

RESULTS: There were 14,228 cases of MPM, of which 3,196 (22%) were women. Despite similar baseline characteristics for both genders, 5-year survival was 13.4% in women and 4.5% in men (p < 0.0001). The effect of female gender on survival persisted when stratified by age (dichotomized at 50 years), stage, or race, but differed depending on treatment. Even when adjusted for age, stage, race, and treatment, female MPM patients experienced longer survival than men (hazard ratio = 0.78; 95% confidence interval 0.75 to 0.82).

CONCLUSIONS: This large data set confirms that although MPM is less common in women, they present with similar stage and are offered similar treatment options compared with men. Nevertheless, survival is far better in women compared with men, independent of confounders such as age, stage, and treatment. Differences in asbestos exposure, tumor biology, and the impact of circulating hormones on host response must be investigated to understand this survival advantage and improve prognosis for patients of both genders.}, } @article {pmid24924397, year = {2015}, author = {Lee, YJ and Lee, YJ and Lee, SH}, title = {Resveratrol and clofarabine induces a preferential apoptosis-activating effect on malignant mesothelioma cells by Mcl-1 down-regulation and caspase-3 activation.}, journal = {BMB reports}, volume = {48}, number = {3}, pages = {166-171}, pmid = {24924397}, issn = {1976-670X}, mesh = {Adenine Nucleotides/*pharmacology ; Apoptosis/*drug effects ; Arabinonucleosides/*pharmacology ; Caspase 3/*metabolism ; Cell Line, Tumor ; Clofarabine ; Down-Regulation/*drug effects ; Enzyme Activation ; Humans ; Mesothelioma/enzymology/metabolism/*pathology ; Myeloid Cell Leukemia Sequence 1 Protein/*metabolism ; Resveratrol ; Stilbenes/*pharmacology ; }, abstract = {We previously demonstrated that resveratrol and clofarabine elicited a marked cytotoxicity on malignant mesothelioma (MM) MSTO-211H cells but not on the corresponding normal mesothelial MeT-5A cells. Little is known of the possible molecules that could be used to predict preferential chemosensitivity on MSTO-211H cells. Resveratrol and clofarabine induced down-regulation of Mcl-1 protein level in MSTO-211H cells. Treatment of cells with cycloheximide in the presence of proteasome inhibitor MG132 suggested that Mcl-1 protein levels were regulated at the post-translational step. The siRNA-based knockdown of Mcl-1 in MSTO-211H cells triggered more growth-inhibiting and apoptosis-inducing effects with the resultant cleavages of procaspase-3 and its substrate PARP, increased caspase-3/7 activity, and increased percentage of apoptotic propensities. However, the majority of the observed changes were not shown in MeT-5A cells. Collectively, these studies indicate that the preferential activation of caspase cascade in malignant cells might have important applications as a therapeutic target for MM.}, } @article {pmid24910640, year = {2014}, author = {Kerger, BD and James, RC and Galbraith, DA}, title = {Tumors that mimic asbestos-related mesothelioma: time to consider a genetics-based tumor registry?.}, journal = {Frontiers in genetics}, volume = {5}, number = {}, pages = {151}, pmid = {24910640}, issn = {1664-8021}, abstract = {The diagnosis of mesothelioma is not always straightforward, despite known immunohistochemical markers and other diagnostic techniques. One reason for the difficulty is that extrapleural tumors resembling mesothelioma may have several possible etiologies, especially in cases with no meaningful history of amphibole asbestos exposure. When the diagnosis of mesothelioma is based on histologic features alone, primary mesotheliomas may resemble various primary or metastatic cancers that have directly invaded the serosal membranes. Some of these metastatic malignancies, particularly carcinomas and sarcomas of the pleura, pericardium and peritoneum, may undergo desmoplastic reaction in the pleura, thereby mimicking mesothelioma, rather than the primary tumor. Encasement of the lung by direct spread or metastasis, termed pseudomesotheliomatous spread, occurs with several other primary cancer types, including certain late-stage tumors from genetic cancer syndromes exhibiting chromosomal instability. Although immunohistochemical staining patterns differentiate most carcinomas, lymphomas, and mestastatic sarcomas from mesotheliomas, specific genetic markers in tumor or somatic tissues have been recently identified that may also distinguish these tumor types from asbestos-related mesothelioma. A registry for genetic screening of mesothelioma cases would help lead to improvements in diagnostic criteria, prognostic accuracy and treatment efficacy, as well as improved estimates of primary mesothelioma incidence and of background rates of cancers unrelated to asbestos that might be otherwise mistaken for mesothelioma. This information would also help better define the dose-response relationships for mesothelioma and asbestos exposure, as well as other risk factors for mesothelioma and other mesenchymal or advanced metastatic tumors that may be indistinguishable by histology and staining characteristics.}, } @article {pmid24885895, year = {2014}, author = {Thompson, JK and Westbom, CM and MacPherson, MB and Mossman, BT and Heintz, NH and Spiess, P and Shukla, A}, title = {Asbestos modulates thioredoxin-thioredoxin interacting protein interaction to regulate inflammasome activation.}, journal = {Particle and fibre toxicology}, volume = {11}, number = {}, pages = {24}, pmid = {24885895}, issn = {1743-8977}, support = {R01 ES021110/ES/NIEHS NIH HHS/United States ; }, mesh = {Acetylcysteine/pharmacology ; Antioxidants/pharmacology ; Apoptosis/drug effects ; Asbestos, Crocidolite/*toxicity ; Blotting, Western ; Caspase 1/metabolism ; Cell Line, Tumor ; Dehydroascorbic Acid/metabolism ; Dinitrochlorobenzene/toxicity ; Enzyme Activation/drug effects ; Epithelium/drug effects/pathology ; Gene Knockdown Techniques ; Humans ; Inflammation/*pathology ; L-Lactate Dehydrogenase/metabolism ; RNA, Small Interfering ; Reactive Oxygen Species/metabolism ; Real-Time Polymerase Chain Reaction ; Thioredoxin Reductase 1/metabolism ; Thioredoxins/*drug effects/genetics ; }, abstract = {BACKGROUND: Asbestos exposure is related to various diseases including asbestosis and malignant mesothelioma (MM). Among the pathogenic mechanisms proposed by which asbestos can cause diseases involving epithelial and mesothelial cells, the most widely accepted one is the generation of reactive oxygen species and/or depletion of antioxidants like glutathione. It has also been demonstrated that asbestos can induce inflammation, perhaps due to activation of inflammasomes.

METHODS: The oxidation state of thioredoxin was analyzed by redox Western blot analysis and ROS generation was assessed spectrophotometrically as a read-out of solubilized formazan produced by the reduction of nitrotetrazolium blue (NTB) by superoxide. Quantitative real time PCR was used to assess changes in gene transcription.

RESULTS: Here we demonstrate that crocidolite asbestos fibers oxidize the pool of the antioxidant, Thioredoxin-1 (Trx1), which results in release of Thioredoxin Interacting Protein (TXNIP) and subsequent activation of inflammasomes in human mesothelial cells. Exposure to crocidolite asbestos resulted in the depletion of reduced Trx1 in human peritoneal mesothelial (LP9/hTERT) cells. Pretreatment with the antioxidant dehydroascorbic acid (a reactive oxygen species (ROS) scavenger) reduced the level of crocidolite asbestos-induced Trx1 oxidation as well as the depletion of reduced Trx1. Increasing Trx1 expression levels using a Trx1 over-expression vector, reduced the extent of Trx1 oxidation and generation of ROS by crocidolite asbestos, and increased cell survival. In addition, knockdown of TXNIP expression by siRNA attenuated crocidolite asbestos-induced activation of the inflammasome.

CONCLUSION: Our novel findings suggest that extensive Trx1 oxidation and TXNIP dissociation may be one of the mechanisms by which crocidolite asbestos activates the inflammasome and helps in development of MM.}, } @article {pmid24885398, year = {2014}, author = {Renganathan, A and Kresoja-Rakic, J and Echeverry, N and Ziltener, G and Vrugt, B and Opitz, I and Stahel, RA and Felley-Bosco, E}, title = {GAS5 long non-coding RNA in malignant pleural mesothelioma.}, journal = {Molecular cancer}, volume = {13}, number = {}, pages = {119}, pmid = {24885398}, issn = {1476-4598}, mesh = {Cell Cycle/genetics ; Cell Line, Tumor ; Cell Proliferation ; *Gene Expression Regulation, Neoplastic ; Genes, Reporter ; Hedgehog Proteins/genetics/metabolism ; Humans ; Ki-67 Antigen/genetics/metabolism ; Luciferases/genetics/metabolism ; Lung Neoplasms/*genetics/metabolism/pathology ; Membrane Glycoproteins/*genetics/metabolism ; Mesothelioma/*genetics/metabolism/pathology ; Mesothelioma, Malignant ; Phosphatidylinositol 3-Kinases/genetics/metabolism ; Phosphoinositide-3 Kinase Inhibitors ; Primary Cell Culture ; Promoter Regions, Genetic ; Protein Kinase Inhibitors/pharmacology ; RNA, Long Noncoding/antagonists & inhibitors/*genetics/metabolism ; RNA, Small Interfering/genetics/metabolism ; Signal Transduction ; TOR Serine-Threonine Kinases/antagonists & inhibitors/genetics/metabolism ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive cancer with short overall survival. Long non-coding RNAs (lncRNA) are a class of RNAs more than 200 nucleotides long that do not code for protein and are part of the 90% of the human genome that is transcribed. Earlier experimental studies in mice showed GAS5 (growth arrest specific transcript 5) gene deletion in asbestos driven mesothelioma. GAS5 encodes for a lncRNA whose function is not well known, but it has been shown to act as glucocorticoid receptor decoy and microRNA "sponge". Our aim was to investigate the possible role of the GAS5 in the growth of MPM.

METHODS: Primary MPM cultures grown in serum-free condition in 3% oxygen or MPM cell lines grown in serum-containing medium were used to investigate the modulation of GAS5 by growth arrest after inhibition of Hedgehog or PI3K/mTOR signalling. Cell cycle length was determined by EdU incorporation assay in doxycycline inducible short hairpinGAS5 clones generated from ZL55SPT cells. Gene expression was quantified by quantitative PCR. To investigate the GAS5 promoter, a 0.77 kb sequence was inserted into a pGL3 reporter vector and luciferase activity was determined after transfection into MPM cells. Localization of GAS5 lncRNA was identified by in situ hybridization. To characterize cells expressing GAS5, expression of podoplanin and Ki-67 was assessed by immunohistochemistry.

RESULTS: GAS5 expression was lower in MPM cell lines compared to normal mesothelial cells. GAS5 was upregulated upon growth arrest induced by inhibition of Hedgehog and PI3K/mTOR signalling in in vitro MPM models. The increase in GAS5 lncRNA was accompanied by increased promoter activity. Silencing of GAS5 increased the expression of glucocorticoid responsive genes glucocorticoid inducible leucine-zipper and serum/glucocorticoid-regulated kinase-1 and shortened the length of the cell cycle. Drug induced growth arrest was associated with GAS5 accumulation in the nuclei. GAS5 was abundant in tumoral quiescent cells and it was correlated to podoplanin expression.

CONCLUSIONS: The observations that GAS5 levels modify cell proliferation in vitro, and that GAS5 expression in MPM tissue is associated with cell quiescence and podoplanin expression support a role of GAS5 in MPM biology.}, } @article {pmid24876951, year = {2014}, author = {Pfau, JC and Serve, KM and Noonan, CW}, title = {Autoimmunity and asbestos exposure.}, journal = {Autoimmune diseases}, volume = {2014}, number = {}, pages = {782045}, pmid = {24876951}, issn = {2090-0422}, support = {P20 GM103408/GM/NIGMS NIH HHS/United States ; R01 TS000099/TS/ATSDR CDC HHS/United States ; }, abstract = {Despite a body of evidence supporting an association between asbestos exposure and autoantibodies indicative of systemic autoimmunity, such as antinuclear antibodies (ANA), a strong epidemiological link has never been made to specific autoimmune diseases. This is in contrast with another silicate dust, crystalline silica, for which there is considerable evidence linking exposure to diseases such as systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis. Instead, the asbestos literature is heavily focused on cancer, including mesothelioma and pulmonary carcinoma. Possible contributing factors to the absence of a stronger epidemiological association between asbestos and autoimmune disease include (a) a lack of statistical power due to relatively small or diffuse exposure cohorts, (b) exposure misclassification, (c) latency of clinical disease, (d) mild or subclinical entities that remain undetected or masked by other pathologies, or (e) effects that are specific to certain fiber types, so that analyses on mixed exposures do not reach statistical significance. This review summarizes epidemiological, animal model, and in vitro data related to asbestos exposures and autoimmunity. These combined data help build toward a better understanding of the fiber-associated factors contributing to immune dysfunction that may raise the risk of autoimmunity and the possible contribution to asbestos-related pulmonary disease.}, } @article {pmid24872671, year = {2013}, author = {Bianchi, C and Bianchi, T}, title = {Pleural mesothelioma in a couple of brothers.}, journal = {Indian journal of occupational and environmental medicine}, volume = {17}, number = {3}, pages = {122-123}, pmid = {24872671}, issn = {0973-2284}, abstract = {Malignant mesotheliomas of the pleura, epithelial type, were observed in two brothers. Both the patients had histories of severe exposure to asbestos, having worked as insulators. The latency periods in the two cases were 26 and 38 years, respectively. Available literature data suggest that mesothelioma occurrence among blood-related people is favored by a genetic predisposition.}, } @article {pmid24868221, year = {2014}, author = {Ahn, S and Choi, IH and Han, J and Kim, J and Ahn, MJ}, title = {Pleural mesothelioma: an institutional experience of 66 cases.}, journal = {Korean journal of pathology}, volume = {48}, number = {2}, pages = {91-99}, pmid = {24868221}, issn = {1738-1843}, abstract = {BACKGROUND: Malignant mesothelioma of the pleura is an aggressive tumor known to be associated with asbestos. Histological diagnosis of mesothelioma is challenging and is usually aided by immunohistochemical markers.

METHODS: During an 18-year period (1995-2012), 66 patients with pleural mesothelioma were diagnosed at the Samsung Medical Center in Seoul. We reviewed hematoxylin and eosin and immunohistochemical slides of pleural mesothelioma and evaluated their pathological and clinical features.

RESULTS: The male-to-female ratio was 1.75:1, and age of patients ranged from 28 to 80 years with an average age of 56.84 years. Twenty-two out of 66 patients underwent curative pneumonectomy. Follow-up data was available in 60 patients (90.9%), and 50 of them (83.3%) died from the disease. The average overall survival was 15.39 months. Histologically, the epithelioid type was the most common, followed by the sarcomatoid and the biphasic types. Epidemiologic information was not available in most cases, and only one patient was confirmed to have a history of asbestos exposure.

CONCLUSIONS: Malignant mesothelioma of the pleura is a fatal tumor, and the therapeutic benefit of pneumonectomy remains unproven. The combination of calretinin, Wilms tumor 1, HMBE-1, and thyroid transcription factor-1 may provide high diagnostic accuracy in diagnosing mesothelioma.}, } @article {pmid24848258, year = {2014}, author = {Shapiro, IM and Kolev, VN and Vidal, CM and Kadariya, Y and Ring, JE and Wright, Q and Weaver, DT and Menges, C and Padval, M and McClatchey, AI and Xu, Q and Testa, JR and Pachter, JA}, title = {Merlin deficiency predicts FAK inhibitor sensitivity: a synthetic lethal relationship.}, journal = {Science translational medicine}, volume = {6}, number = {237}, pages = {237ra68}, pmid = {24848258}, issn = {1946-6242}, support = {R01 CA113733/CA/NCI NIH HHS/United States ; R01 CA148805/CA/NCI NIH HHS/United States ; R01CA113733/CA/NCI NIH HHS/United States ; CA148805/CA/NCI NIH HHS/United States ; }, mesh = {Aldehyde Dehydrogenase/metabolism ; Animals ; Antineoplastic Agents/*pharmacology ; Apoptosis/drug effects ; Cell Adhesion/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Dose-Response Relationship, Drug ; Focal Adhesion Kinase 1/*antagonists & inhibitors/genetics/metabolism ; Humans ; Lung Neoplasms/*drug therapy/enzymology/genetics/pathology ; Mesothelioma/*drug therapy/enzymology/genetics/pathology ; Mesothelioma, Malignant ; Mice ; Molecular Targeted Therapy ; Neoplastic Stem Cells/drug effects/enzymology ; Neurofibromin 2/*deficiency/genetics ; Protein Kinase Inhibitors/*pharmacology ; RNA Interference ; Signal Transduction/drug effects ; Time Factors ; Transfection ; Tumor Burden/drug effects ; Xenograft Model Antitumor Assays ; }, abstract = {The goal of targeted therapy is to match a selective drug with a genetic lesion that predicts for drug sensitivity. In a diverse panel of cancer cell lines, we found that the cells most sensitive to focal adhesion kinase (FAK) inhibition lack expression of the neurofibromatosis type 2 (NF2) tumor suppressor gene product, Merlin. Merlin expression is often lost in malignant pleural mesothelioma (MPM), an asbestos-induced aggressive cancer with limited treatment options. Our data demonstrate that low Merlin expression predicts for increased sensitivity of MPM cells to a FAK inhibitor, VS-4718, in vitro and in tumor xenograft models. Disruption of MPM cell-cell or cell-extracellular matrix (ECM) contacts with blocking antibodies suggests that weak cell-cell adhesions in Merlin-negative MPM cells underlie their greater dependence on cell-ECM-induced FAK signaling. This provides one explanation of why Merlin-negative cells are vulnerable to FAK inhibitor treatment. Furthermore, we validated aldehyde dehydrogenase as a marker of cancer stem cells (CSCs) in MPM, a cell population thought to mediate tumor relapse after chemotherapy. Whereas pemetrexed and cisplatin, standard-of-care agents for MPM, enrich for CSCs, FAK inhibitor treatment preferentially eliminates these cells. These preclinical results provide the rationale for a clinical trial in MPM patients using a FAK inhibitor as a single agent after first-line chemotherapy. With this design, the FAK inhibitor could potentially induce a more durable clinical response through reduction of CSCs along with a strong antitumor effect. Furthermore, our data suggest that patients with Merlin-negative tumors may especially benefit from FAK inhibitor treatment.}, } @article {pmid24842786, year = {2014}, author = {Reid, A and de Klerk, NH and Magnani, C and Ferrante, D and Berry, G and Musk, AW and Merler, E}, title = {Mesothelioma risk after 40 years since first exposure to asbestos: a pooled analysis.}, journal = {Thorax}, volume = {69}, number = {9}, pages = {843-850}, doi = {10.1136/thoraxjnl-2013-204161}, pmid = {24842786}, issn = {1468-3296}, mesh = {Adolescent ; Adult ; Asbestos, Crocidolite/*toxicity ; Asbestos, Serpentine/*toxicity ; Australia/epidemiology ; Child ; Child, Preschool ; Cohort Studies ; Female ; Follow-Up Studies ; Humans ; Inhalation Exposure/*adverse effects ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Exposure/*adverse effects ; Peritoneal Neoplasms/*epidemiology/etiology ; Pleural Neoplasms/*epidemiology/etiology ; Time Factors ; Young Adult ; }, abstract = {BACKGROUND: The risk of malignant mesothelioma (MM) increases proportionally to the cumulative exposure, and to the 3rd or 4th power of time since first exposed, to asbestos. However, little is known about the risk of MM after more than 40 years since first exposure because most epidemiological studies do not have follow-up for sufficient periods of time.

METHODS: The data from six cohort studies of exposed workers and two cohorts with residential exposure have been pooled. A nested case control design matched cases and controls on calendar period and age. Conditional logistic regression modelled the relationship between time since first exposure and risk of MM.

RESULTS: The combined data consisted of 22,048 people with asbestos exposure (5769 women), 707 cases of pleural MM (165 in women) and 155 cases of peritoneal MM (32 in women). Median time since first exposure for pleural MM cases was 38.4 years (IQR 31.3-45.3). Median duration of exposure for pleural MM cases was 3.75 years (IQR 0.7-18.2). The rate and risk of pleural MM increased until 45 years following first exposure and then appeared to increase at a slower power of time since first exposure. The rate of increase in peritoneal MM over the 10-50 years since first exposure continued to increase.

CONCLUSIONS: Exposure to asbestos confers a long-term risk of developing pleural and peritoneal mesothelioma which increases following cessation of exposure. While the rate of increase appears to start to level out after 40-50 years no one survives long enough for the excess risk to disappear.}, } @article {pmid24842043, year = {2014}, author = {Sezer, A and Sümbül, AT and Abalı, H and Mertsoylu, H and Ozyılkan, O}, title = {Malignant pleural mesothelioma: a single-center experience in Turkey.}, journal = {Medical science monitor : international medical journal of experimental and clinical research}, volume = {20}, number = {}, pages = {825-832}, pmid = {24842043}, issn = {1643-3750}, mesh = {Adult ; Aged ; Demography ; Disease-Free Survival ; Female ; Humans ; Lung Neoplasms/*epidemiology/therapy ; Male ; Mesothelioma/*epidemiology/therapy ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/*epidemiology/therapy ; Turkey/epidemiology ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma is a rare lethal malignancy caused by asbestos exposure. It is more frequently seen in certain regions in Turkey. In this retrospective study, we aimed to analyse demographic, clinical, and pathological data and treatment-related features in 54 patients.

MATERIAL AND METHODS: The study included 54 patients diagnosed with malignant mesothelioma that were followed and treated.

RESULT: Of the 54 patients, 34 (55.6%) were male. The median age in men and women were 60.3 (38.2-77.2) and 65.8 (37.7-77.5) years, respectively. In 35 (64.8%), exposure to asbestosis was present. Epithelial type was found in 27 (50.0%), followed by mixed type in 7 (13.0%) patients, and in 20 (37.0%) patients the subtype could not be determined. The disease was staged as IV in 37 (68.5%) patients. In 28 patients (51.9%), it was right-sided and in 1 (1.9%) it was bilateral. The most frequent metastatic sites (in decreasing order) were lungs, mediastinum, diaphragm, liver, and thoracal wall. Of the 54 patients, 36 (66.6%) received 1st-line chemotherapy and 20 (37%) 2nd-line chemotherapy. Eighteen patients (33.3%) received radiotherapy; 11 (20.3%) with palliative intention and 7 (12.9%) with curative intention. Median overall survival (OS) was 12.03 months (95% CI 7.2-16.8). OS was not affected by sex (p=0.32), smoking history (p=0.51), alcohol consumption (p=0.36), family history (p=0.67), pleural effusion presence (p=0.80), operation (p=0.14), clinical stage (p=0.072), symptom at presentation (p=0.66), having mixed type histology (p=0.079), asbestos exposure (p=0.06), and type of 1st-line chemotherapy (p=0.161). On the contrary, it may be positively affected by good ECOG PS (0-1) (p<0.01), age below 65 (p=0.03), left-sided disease (p=0.01), receiving chemotherapy (p<0.01), having unilateral pleural effusion (p=0.018), and type of 2nd-line chemotherapy (p=0.025).

CONCLUSIONS: OS of our patients was better than that found in the literature, seeming to be positively affected by early stages, better ECOG PS, age below 65 years, left side involvement, and having second-line chemotherapy with cisplatin-gemcitabine or 3M. Overall treatment success seems to be comparable to what is currently expected.}, } @article {pmid24839947, year = {2014}, author = {Jiang, L and Yamashita, Y and Chew, SH and Akatsuka, S and Ukai, S and Wang, S and Nagai, H and Okazaki, Y and Takahashi, T and Toyokuni, S}, title = {Connective tissue growth factor and β-catenin constitute an autocrine loop for activation in rat sarcomatoid mesothelioma.}, journal = {The Journal of pathology}, volume = {233}, number = {4}, pages = {402-414}, doi = {10.1002/path.4377}, pmid = {24839947}, issn = {1096-9896}, mesh = {Animals ; Autocrine Communication/*physiology ; Biomarkers, Tumor/metabolism ; Connective Tissue Growth Factor/*metabolism ; Disease Models, Animal ; Epithelial-Mesenchymal Transition/physiology ; Epithelium/metabolism/pathology ; Female ; Glycogen Synthase Kinase 3/metabolism ; Glycogen Synthase Kinase 3 beta ; Lung Neoplasms/metabolism/pathology/*physiopathology ; Male ; Mesothelioma/metabolism/pathology/*physiopathology ; Mesothelioma, Malignant ; Rats ; Rats, Inbred F344 ; Sarcoma/metabolism/pathology/*physiopathology ; Signal Transduction/physiology ; TCF Transcription Factors/metabolism ; beta Catenin/*metabolism ; }, abstract = {Due to the formerly widespread use of asbestos, malignant mesothelioma (MM) is increasingly frequent worldwide. MM is classified into epithelioid (EM), sarcomatoid (SM), and biphasic subtypes. SM is less common than EM but is recognized as the most aggressive type of MM, and these patients have a poor prognosis. To identify genes responsible for the aggressiveness of SM, we induced EM and SM in rats, using asbestos, and compared their transcriptomes. Based on the results, we focused on connective tissue growth factor (Ctgf), whose expression was significantly increased in SM compared with EM; EM itself exhibited an increased expression of Ctgf compared with normal mesothelium. Particularly in SM, Ctgf was a major regulator of MM proliferation and invasion through activation of the β-catenin-TCF-LEF signalling pathway, which is autocrine and formed a positive feedback loop via LRP6 as a receptor for secreted Ctgf. High Ctgf expression also played a role in the epithelial-mesenchymal transition in MM. Furthermore, Ctgf is a novel serum biomarker for both early diagnosis and determining the MM prognosis in rats. These data link Ctgf to SM through the LRP6-GSK3β-β-catenin-TCF-Ctgf autocrine axis and suggest Ctgf as a therapeutic target.}, } @article {pmid24837247, year = {2014}, author = {Wu, WT and Lin, YJ and Shiue, HS and Li, CY and Tsai, PJ and Yang, CY and Liou, SH and Wu, TN}, title = {Cancer incidence of Taiwanese shipbreaking workers who have been potentially exposed to asbestos.}, journal = {Environmental research}, volume = {132}, number = {}, pages = {370-378}, doi = {10.1016/j.envres.2014.04.026}, pmid = {24837247}, issn = {1096-0953}, mesh = {Adult ; Asbestos/*adverse effects ; Follow-Up Studies ; Humans ; Incidence ; Male ; Neoplasms/*epidemiology/etiology ; Occupational Exposure/*adverse effects ; *Registries ; Retrospective Studies ; Taiwan/epidemiology ; }, abstract = {BACKGROUND: Shipbreaking remains one of the most dangerous jobs worldwide. Shipbreaking workers are exposed to many hazardous chemicals, especially asbestos. Unfortunately, long-term follow-up studies of cancer incidence patterns in shipbreaking workers are lacking. This study examines whether there is an increased risk of cancer among male shipbreaking workers over a 24-year follow-up period.

METHODS: 4155 male shipbreaking worker's information was retrospectively collected from Kaohsiung's Shipbreaking Workers Union database from 1985. The study cohort was linked to the Taiwan Cancer Registry from 1985 to 2008 for new cancer cases. The expected number of cancers for shipbreaking workers was calculated by using the age (5-year intervals) and calendar time-specific annual rates of cancer incidence with reference to the general population of Taiwan from 1985 to 2008. Standardized incidence ratios (SIRs) were calculated as relative risk estimates. The hazard ratio (HR) for cancer was calculated for the shipbreaking workers with Total Exposure Potential Scores for asbestos.

RESULTS: After consideration of a 5-year latency period, an elevated incidence of overall cancer (N=368; SIR=1.13 (1.01-1.25)), oral cavity cancer (N=83; SIR=1.99 (1.58-2.46)), and trachea, bronchus, and lung cancers (N=53; SIR=1.36 (1.02-1.78)) was found among male shipbreaking employees. Moreover, mesothelioma cases were found in those who had the occupation of flame cutter. The high asbestos exposure group was associated with an increased SIR of developing overall cancer and oral cancer, whether we considered a 5-year or 10-year latency period.

CONCLUSION: Asbestos-related diseases, including lung cancer and mesothelioma, were seen in excess in these shipbreaking workers and some cases appeared to have a dose-dependent relationship. Preventative measures among male shipbreaking workers should be researched further.}, } @article {pmid24830353, year = {2015}, author = {Dodson, RF and Hammar, SP}, title = {Analysis of asbestos concentration in 20 cases of pseudomesotheliomatous lung cancer.}, journal = {Ultrastructural pathology}, volume = {39}, number = {1}, pages = {13-22}, doi = {10.3109/01913123.2014.906525}, pmid = {24830353}, issn = {1521-0758}, mesh = {Adenocarcinoma/chemistry/*etiology/*pathology/ultrastructure ; Adult ; Aged ; Asbestos/adverse effects/*analysis ; Diagnosis, Differential ; Humans ; Lung Neoplasms/chemistry/*etiology/*pathology/ultrastructure ; Male ; Mesothelioma/chemistry/*etiology/ultrastructure ; Mesothelioma, Malignant ; Microscopy, Electron, Transmission ; Middle Aged ; }, abstract = {Mesothelioma is a rare neoplasm caused by asbestos exposure. The majority of mesotheliomas arise from the pleural lining of the thoracic cavity, but also involve the peritoneal and pericardial cavities. Another type of neoplasm referred to as pseudomesotheliomatous adenocarcinoma is rare. Most "pseudomesotheliomas" arise in the pleural tissue of the chest cavity and resemble pleural mesotheliomas, macroscopically and histologically. While most arise in the pleura, there are some that metastasize to the pleura from another site. We evaluated asbestos fiber concentrations in 20 cases of pseudomesotheliomatous lung cancer and found a significant number to contain an elevated concentration of asbestos in their lung tissue, which is similar with our study of 55 mesothelioma cases published in 1997. This would provide evidence that some pseudomesotheliomatous lung cancers are caused by asbestos.}, } @article {pmid24815191, year = {2014}, author = {Xu, J and Alexander, DB and Futakuchi, M and Numano, T and Fukamachi, K and Suzui, M and Omori, T and Kanno, J and Hirose, A and Tsuda, H}, title = {Size- and shape-dependent pleural translocation, deposition, fibrogenesis, and mesothelial proliferation by multiwalled carbon nanotubes.}, journal = {Cancer science}, volume = {105}, number = {7}, pages = {763-769}, pmid = {24815191}, issn = {1349-7006}, mesh = {Animals ; Cell Proliferation/drug effects ; Cytokines/metabolism ; Fibrosis/*chemically induced/pathology ; Inflammation/chemically induced/metabolism/pathology ; Lung/drug effects/metabolism/pathology ; Male ; Mesothelioma/chemically induced/pathology ; Nanotubes, Carbon/*toxicity ; Pleural Cavity/drug effects/*pathology ; Rats ; Rats, Inbred F344 ; }, abstract = {Multiwalled carbon nanotubes (MWCNT) have a fibrous structure similar to asbestos, raising concern that MWCNT exposure may lead to asbestos-like diseases. Previously we showed that MWCNT translocated from the lung alveoli into the pleural cavity and caused mesothelial proliferation and fibrosis in the visceral pleura. Multiwalled carbon nanotubes were not found in the parietal pleura, the initial site of development of asbestos-caused pleural diseases in humans, probably due to the short exposure period of the study. In the present study, we extended the exposure period to 24 weeks to determine whether the size and shape of MWCNT impact on deposition and lesion development in the pleura and lung. Two different MWCNTs were chosen for this study: a larger sized needle-like MWCNT (MWCNT-L; l = 8 μm, d = 150 nm), and a smaller sized MWCNT (MWCNT-S; l = 3 μm, d = 15 nm), which forms cotton candy-like aggregates. Both MWCNT-L and MWCNT-S suspensions were administered to the rat lung once every 2 weeks for 24 weeks by transtracheal intrapulmonary spraying. It was found that MWCNT-L, but not MWCNT-S, translocated into the pleural cavity, deposited in the parietal pleura, and induced fibrosis and patchy parietal mesothelial proliferation lesions. In addition, MWCNT-L induced stronger inflammatory reactions including increased inflammatory cell number and cytokine/chemokine levels in the pleural cavity lavage than MWCNT-S. In contrast, MWCNT-S induced stronger inflammation and higher 8-hydroxydeoxyguanosine level in the lung tissue than MWCNT-L. These results suggest that MWCNT-L has higher risk of causing asbestos-like pleural lesions relevant to mesothelioma development.}, } @article {pmid24806876, year = {2014}, author = {Moolgavkar, SH and Anderson, EL and Chang, ET and Lau, EC and Turnham, P and Hoel, DG}, title = {A review and critique of U.S. EPA's risk assessments for asbestos.}, journal = {Critical reviews in toxicology}, volume = {44}, number = {6}, pages = {499-522}, doi = {10.3109/10408444.2014.902423}, pmid = {24806876}, issn = {1547-6898}, mesh = {Aluminum Silicates/toxicity ; Asbestos, Amphibole/*standards/*toxicity ; Endpoint Determination ; Humans ; Inhalation Exposure/*adverse effects ; Lung Neoplasms/chemically induced/pathology ; Mesothelioma/chemically induced/pathology ; Occupational Exposure/*adverse effects ; Ohio ; Risk Assessment ; Risk Factors ; Smoking/adverse effects ; United States ; United States Environmental Protection Agency/*legislation & jurisprudence ; }, abstract = {U.S. Environmental Protection Agency (EPA) recently conducted a risk assessment for exposure to Libby amphibole asbestos that is precedent-setting for two reasons. First, the Agency has not previously conducted a risk assessment for a specific type of asbestos fiber. Second, the risk assessment includes not only an inhalation unit risk (IUR) for the cancer endpoints, but also a reference concentration (RfC) for nonmalignant disease. In this paper, we review the procedures used by the Agency for both cancer and nonmalignant disease and discuss the strengths and limitations of these procedures. The estimate of the RfC uses the benchmark dose method applied to pleural plaques in a small subcohort of vermiculite workers in Marysville, Ohio. We show that these data are too sparse to inform the exposure-response relationship in the low-exposure region critical for estimation of an RfC, and that different models with very different exposure-response shapes fit the data equally well. Furthermore, pleural plaques do not represent a disease condition and do not appear to meet the EPA's definition of an adverse condition. The estimation of the IUR for cancer is based on a subcohort of Libby miners, discarding the vast majority of lung cancers and mesotheliomas in the entire cohort and ignoring important time-related factors in exposure and risk, including effect modification by age. We propose that an IUR based on an endpoint that combines lung cancer, mesothelioma, and nonmalignant respiratory disease (NMRD) in this cohort would protect against both malignant and nonmalignant disease. However, the IUR should be based on the entire cohort of Libby miners, and the analysis should properly account for temporal factors. We illustrate our discussion with our own independent analyses of the data used by the Agency.}, } @article {pmid24794734, year = {2014}, author = {Kozlowski, D and Provost, SC and Tucker, J and van der Zwan, R}, title = {Dusted community: piloting a virtual peer-to-peer support community for people with an asbestos-related diagnosis and their families.}, journal = {Journal of psychosocial oncology}, volume = {32}, number = {4}, pages = {463-475}, doi = {10.1080/07347332.2014.917142}, pmid = {24794734}, issn = {1540-7586}, mesh = {Asbestos/*adverse effects ; Caregivers/*psychology ; Female ; Humans ; *Internet ; Interpersonal Relations ; Male ; Mesothelioma/*etiology/*psychology ; *Peer Group ; Pilot Projects ; Program Evaluation ; Social Isolation/psychology ; *Social Support ; }, abstract = {Individuals with an asbestos-related diagnosis and their carers face burdens including debilitating and life-limiting physical symptoms and medico-legal stressors. Feelings of social isolation are common. Increasing social connectedness can lead to increased feelings of personal empowerment and may inhibit chronic stress responses. The authors report on the development, via a process of participatory action research, of an online peer-to-peer support group, and the first 30-day test phase of this virtual community. Initial indications are that individuals with an asbestos-related diagnosis and their carers can benefit, in psychosocial terms, from membership of an on-line support group comprised of experientially similar others.}, } @article {pmid24781281, year = {2014}, author = {Consonni, D and Barone-Adesi, F and Mensi, C}, title = {Comment on 'The latency period of mesothelioma among a cohort of British asbestos workers (1978-2005)': methodological problems with case-only survival analysis.}, journal = {British journal of cancer}, volume = {111}, number = {8}, pages = {1674}, pmid = {24781281}, issn = {1532-1827}, mesh = {Asbestos/*adverse effects ; Female ; Humans ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology ; Occupational Exposure/*adverse effects ; }, } @article {pmid24781044, year = {2015}, author = {Jakubec, P and Pelclova, D and Smolkova, P and Kolek, V and Nakladalova, M}, title = {Significance of serum mesothelin in an asbestos-exposed population in the Czech Republic.}, journal = {Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia}, volume = {159}, number = {3}, pages = {472-479}, doi = {10.5507/bp.2014.015}, pmid = {24781044}, issn = {1804-7521}, mesh = {Asbestos/*adverse effects ; Asbestosis/*blood/complications/epidemiology ; Biomarkers, Tumor/blood ; Czech Republic/epidemiology ; Female ; GPI-Linked Proteins/*blood ; Humans ; Incidence ; Lung Neoplasms/*blood/epidemiology/etiology ; Male ; Mesothelin ; Mesothelioma/*blood/epidemiology/etiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*blood/epidemiology/etiology ; ROC Curve ; }, abstract = {AIMS: Pleural mesothelioma is a highly aggressive and difficult-to-treat form of cancer induced by asbestos in 80-90% of cases. The population group most at risk of the condition are asbestos-exposed workers. Mesothelin or soluble mesothelin-related protein (SMRP) is studied as a potential marker of mesothelioma in the at-risk population.

METHODS: The study comprised 239 subjects with a mean duration of occupational exposure to asbestos of 19.9 years. In all of them, a complete medical history was taken, focused on exposure duration and a physical examination, a chest X-ray or other imaging investigations and a lung function test were performed. Their serum SMRP levels were measured and biopsy samples were taken to diagnose pleural disease. Based on the above examinations, the subjects were classified into subgroups and serum SMRP concentrations were statistically analyzed with respect to individual parameters.

RESULTS: In asbestos-exposed individuals, mesothelin levels were significantly higher in those with pathological X-ray findings than in those with normal X-ray results (0.78 ± 0.63 vs. 0.50 ± 0.35, P<0.0001). The group of patients with benign disease had statistically significantly higher mesothelin levels than those with normal X-ray findings (0.755 ± 0.543 vs. 0.50 ± 0.35, P<0.001). In the group with present malignant processes, mesothelin levels were higher than in individuals with benign disease (1.19 ± 0.89 vs. 0.76 ± 0.54, P=0.015). Only a weak correlation was found between mesothelin levels and asbestos exposure duration. There were relatively high sensitivity and high specificity (75% and 90.6%, respectively) of serum mesothelin for pleural mesothelioma. However, given the small number of mesothelioma cases in the group, the results cannot be considered as statistically significant.

CONCLUSIONS: In persons followed up for asbestos exposure, increased mesothelin levels signalize pathological processes in the chest and correlate with severity of the disease. The study suggests that mesothelin cannot be considered a reliable marker for the early stage of malignant degeneration of pleural disease but only an additional criterion for examination of the followed-up individuals.}, } @article {pmid24780577, year = {2014}, author = {Baas, P and Burgers, JA}, title = {[Is one single exposure to asbestos life-threatening?].}, journal = {Nederlands tijdschrift voor geneeskunde}, volume = {158}, number = {}, pages = {A7653}, pmid = {24780577}, issn = {1876-8784}, mesh = {Asbestos/*toxicity ; Carcinoma/*epidemiology ; Humans ; Laryngeal Neoplasms/*epidemiology ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*epidemiology ; }, abstract = {The media occasionally reports on possible asbestos exposure during demolition of houses in an urban setting. The risk for the development of any asbestos-related cancer in these settings is considered to be lower than for that in occupational exposure. Offermans et al. examined a Dutch cohort of 58,279 workers in the period from 1986 to 2007. They concluded that the risk of lung cancer, laryngeal cancer and mesothelioma increased with exposure to asbestos. The risk of development of lung cancer was higher for anyone with increased years of exposure to asbestos fibre combined with a smoking habit. The study was well conducted, but exact data on fibre concentration and type of asbestos are lacking. We suggest that occasional exposure to asbestos poses hardly any risk for the general population. However, rules and regulations for the removal of asbestos-containing material remain important as asbestos exposure remains a serious health risk, especially in smokers.}, } @article {pmid24778081, year = {2014}, author = {Varesano, S and Leo, C and Boccardo, S and Salvi, S and Truini, M and Ferro, P and Fedeli, F and Canessa, PA and Dessanti, P and Pistillo, MP and Roncella, S}, title = {Status of Anaplastic Lymphoma Kinase (ALK) in malignant mesothelioma.}, journal = {Anticancer research}, volume = {34}, number = {5}, pages = {2589-2592}, pmid = {24778081}, issn = {1791-7530}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anaplastic Lymphoma Kinase ; Child ; Child, Preschool ; Female ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Lung Neoplasms/*enzymology/*genetics ; Male ; Mesothelioma/*enzymology/*genetics ; Mesothelioma, Malignant ; Middle Aged ; Mutation ; Receptor Protein-Tyrosine Kinases/*biosynthesis/*genetics ; Young Adult ; }, abstract = {BACKGROUND: Malignant mesothelioma (MM) is a particularly aggressive type of primary tumor, associated with exposure to asbestos, and characterized by high mortality. To date, there is no curative therapy for MM. The receptor anaplastic lymphoma kinase (ALK) was found to be mutated in many cases of cancer and used as a target in biological therapies. We investigated whether this pharmacological treatment could also be applicable to MM.

MATERIALS AND METHODS: The state of ALK was analyzed by immunohistochemistry and fluorescent in situ hybridization in 63 MM tissue specimens.

RESULTS: None of the 63 MM samples showed overexpression or translocation of ALK.

CONCLUSION: Our preliminary data exclude the utility of analysis of the ALK gene in MM and suggest that ALK inhibitor therapy is not applicable to MM.}, } @article {pmid24766058, year = {2014}, author = {Boffetta, P and Donaldson, K and Moolgavkar, S and Mandel, JS}, title = {A systematic review of occupational exposure to synthetic vitreous fibers and mesothelioma.}, journal = {Critical reviews in toxicology}, volume = {44}, number = {5}, pages = {436-449}, doi = {10.3109/10408444.2014.899558}, pmid = {24766058}, issn = {1547-6898}, mesh = {Animals ; Asbestos/*toxicity ; Canada/epidemiology ; Disease Models, Animal ; Europe/epidemiology ; Half-Life ; Humans ; Incidence ; Mesothelioma/*epidemiology/etiology/*pathology ; Mineral Fibers/*toxicity ; Occupational Exposure/*adverse effects ; Rats ; Risk Assessment ; Toxicity Tests ; United States/epidemiology ; }, abstract = {OBJECTIVE: We investigated whether available epidemiological and toxicological data suggest an increased risk of mesothelioma among workers exposed to synthetic vitreous fibers (SVF).

METHODS: We conducted a systematic review of epidemiological studies on the risk of mesothelioma among workers exposed to SVF, and toxicological studies on SVF and mesothelioma.

RESULTS: Seven cohort studies were conducted among workers employed in production of rock/slag wool, glass wool, or continuous glass filament in the United States, Canada, and Europe. Of the six deaths from mesothelioma identified in these studies, three had exposure to asbestos. A review of death certificates in a study of rock wool production workers identified one additional probable death. A formal comparison with expected deaths is not feasible. Four community-based case-control studies were identified, of which three reported an increased risk among SVF-exposed workers. The number of cases not exposed to asbestos was less, and residual confounding from asbestos exposure misclassification may explain the association in these studies. The toxicology review of SVF suggested that they present a low hazard mostly due to their low biopersistence, typically with a half-life in rat studies of tens of days compared to amphibole asbestos which has a half-life of 400-500 days.

CONCLUSIONS: The combined evidence from epidemiology and toxicology provide little evidence that exposure to SVF increases the risk of mesothelioma.}, } @article {pmid24762959, year = {2014}, author = {Zhou, S and Liu, L and Li, H and Eilers, G and Kuang, Y and Shi, S and Yan, Z and Li, X and Corson, JM and Meng, F and Zhou, H and Sheng, Q and Fletcher, JA and Ou, WB}, title = {Multipoint targeting of the PI3K/mTOR pathway in mesothelioma.}, journal = {British journal of cancer}, volume = {110}, number = {10}, pages = {2479-2488}, pmid = {24762959}, issn = {1532-1827}, mesh = {Antineoplastic Agents/*pharmacology ; Butadienes/pharmacology ; Cell Cycle/drug effects ; Cell Line, Tumor ; Chromones/pharmacology ; Drug Screening Assays, Antitumor ; Enzyme Activation/drug effects ; Everolimus ; Humans ; Imidazoles/pharmacology ; Indazoles/pharmacology ; MAP Kinase Signaling System ; Mesothelioma/*enzymology/pathology ; Molecular Targeted Therapy ; Morpholines/pharmacology ; Neoplasm Proteins/*antagonists & inhibitors/physiology ; Nitriles/pharmacology ; Phosphatidylinositol 3-Kinases/physiology ; *Phosphoinositide-3 Kinase Inhibitors ; Protein Kinase Inhibitors/*pharmacology ; Quinolines/pharmacology ; RNA Interference ; RNA, Small Interfering/pharmacology ; Receptor Protein-Tyrosine Kinases/physiology ; Signal Transduction/*drug effects ; Sirolimus/analogs & derivatives/pharmacology ; Sulfonamides/pharmacology ; TOR Serine-Threonine Kinases/*antagonists & inhibitors/physiology ; raf Kinases/physiology ; }, abstract = {BACKGROUND: Mesothelioma is a notoriously chemotherapy-resistant neoplasm, as is evident in the dismal overall survival for patients with those of asbestos-associated disease. We previously demonstrated co-activation of multiple receptor tyrosine kinases (RTKs), including epidermal growth factor receptor (EGFR), MET, and AXL in mesothelioma cell lines, suggesting that these kinases could serve as novel therapeutic targets. Although clinical trials have not shown activity for EGFR inhibitors in mesothelioma, concurrent inhibition of various activated RTKs has pro-apoptotic and anti-proliferative effects in mesothelioma cell lines. Thus, we hypothesised that a coordinated network of multi-RTK activation contributes to mesothelioma tumorigenesis.

METHODS: Activation of PI3K/AKT/mTOR, Raf/MAPK, and co-activation of RTKs were evaluated in mesotheliomas. Effects of RTK and downstream inhibitors/shRNAs were assessed by measuring mesothelioma cell viability/growth, apoptosis, activation of signalling intermediates, expression of cell-cycle checkpoints, and cell-cycle alterations.

RESULTS: We demonstrate activation of the PI3K/AKT/p70S6K and RAF/MEK/MAPK pathways in mesothelioma, but not in non-neoplastic mesothelial cells. The AKT activation, but not MAPK activation, was dependent on coordinated activation of RTKs EGFR, MET, and AXL. In addition, PI3K/AKT/mTOR pathway inhibition recapitulated the anti-proliferative effects of concurrent inhibition of EGFR, MET, and AXL. Dual targeting of PI3K/mTOR by BEZ235 or a combination of RAD001 and AKT knockdown had a greater effect on mesothelioma proliferation and viability than inhibition of individual activated RTKs or downstream signalling intermediates. Inhibition of PI3K/AKT was also associated with MDM2-p53 cell-cycle regulation.

CONCLUSIONS: These findings show that PI3K/AKT/mTOR is a crucial survival pathway downstream of multiple activated RTKs in mesothelioma, underscoring that PI3K/mTOR is a compelling target for therapeutic intervention.}, } @article {pmid24755344, year = {2014}, author = {Neshatian, L and Halland, M and Arora, AS}, title = {Abdominal pain and bloating in an auto mechanic.}, journal = {Gastroenterology}, volume = {146}, number = {7}, pages = {1610-1611}, doi = {10.1053/j.gastro.2014.02.052}, pmid = {24755344}, issn = {1528-0012}, mesh = {Abdominal Pain/*etiology ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Asbestos/*adverse effects ; *Automobiles ; Biopsy ; Gastric Dilatation/*etiology ; Humans ; Lung Neoplasms/diagnosis/drug therapy/*etiology ; Male ; Mesothelioma/diagnosis/drug therapy/*etiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/*adverse effects ; *Occupations ; Peritoneal Neoplasms/diagnosis/drug therapy/*etiology ; Predictive Value of Tests ; Risk Factors ; Tomography, X-Ray Computed ; }, } @article {pmid24747072, year = {2014}, author = {Komiya, E and Ohnuma, K and Yamazaki, H and Hatano, R and Iwata, S and Okamoto, T and Dang, NH and Yamada, T and Morimoto, C}, title = {CD26-mediated regulation of periostin expression contributes to migration and invasion of malignant pleural mesothelioma cells.}, journal = {Biochemical and biophysical research communications}, volume = {447}, number = {4}, pages = {609-615}, doi = {10.1016/j.bbrc.2014.04.037}, pmid = {24747072}, issn = {1090-2104}, mesh = {Active Transport, Cell Nucleus ; Cell Adhesion Molecules/genetics/*metabolism ; Cell Line, Tumor ; Cell Movement/physiology ; Dipeptidyl Peptidase 4/genetics/*metabolism ; Gene Knockdown Techniques ; Humans ; Lung Neoplasms/genetics/*metabolism/*pathology ; Mesothelioma/genetics/*metabolism/*pathology ; Mesothelioma, Malignant ; Neoplasm Invasiveness/pathology/physiopathology ; Nuclear Proteins/metabolism ; Pleural Neoplasms/genetics/*metabolism/*pathology ; Protein Kinase Inhibitors/pharmacology ; Pyrimidines/pharmacology ; RNA, Messenger/genetics/metabolism ; RNA, Neoplasm/genetics/metabolism ; RNA, Small Interfering/genetics ; Twist-Related Protein 1/metabolism ; Up-Regulation ; src-Family Kinases/antagonists & inhibitors/metabolism ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive malignancy arising from mesothelial lining of pleura. It is generally associated with a history of asbestos exposure and has a very poor prognosis, partly due to the lack of a precise understanding of the molecular mechanisms associated with its malignant behavior. In the present study, we expanded on our previous studies on the enhanced motility and increased CD26 expression in MPM cells, with a particular focus on integrin adhesion molecules. We found that expression of CD26 upregulates periostin secretion by MPM cells, leading to enhanced MPM cell migratory and invasive activity. Moreover, we showed that upregulation of periostin expression results from the nuclear translocation of the basic helix-loop-helix transcription factor Twist1, a process that is mediated by CD26-associated activation of Src phosphorylation. While providing new and profound insights into the molecular mechanisms involved in MPM biology, these findings may also lead to the development of novel therapeutic strategies for MPM.}, } @article {pmid24735948, year = {2014}, author = {Lin, Z and Liu, T and Kamp, DW and Wang, Y and He, H and Zhou, X and Li, D and Yang, L and Zhao, B and Liu, G}, title = {AKT/mTOR and c-Jun N-terminal kinase signaling pathways are required for chrysotile asbestos-induced autophagy.}, journal = {Free radical biology & medicine}, volume = {72}, number = {}, pages = {296-307}, pmid = {24735948}, issn = {1873-4596}, support = {I01 BX000786/BX/BLRD VA/United States ; R01 ES020357/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Asbestos, Serpentine/*toxicity ; Autophagy/*physiology ; Blotting, Western ; Cell Line ; Coculture Techniques ; Epithelial Cells/drug effects/metabolism ; Fibroblasts/cytology ; Fluorescent Antibody Technique ; Humans ; JNK Mitogen-Activated Protein Kinases/*metabolism ; Lung/drug effects/metabolism ; Mice ; Microscopy, Electron, Transmission ; Proto-Oncogene Proteins c-akt/*metabolism ; RNA, Small Interfering ; Real-Time Polymerase Chain Reaction ; Signal Transduction/*physiology ; TOR Serine-Threonine Kinases/*metabolism ; Transfection ; }, abstract = {Chrysotile asbestos is closely associated with excess mortality from pulmonary diseases such as lung cancer, mesothelioma, and asbestosis. Although multiple mechanisms in which chrysotile asbestos fibers induce pulmonary disease have been identified, the role of autophagy in human lung epithelial cells has not been examined. In this study, we evaluated whether chrysotile asbestos induces autophagy in A549 human lung epithelial cells and then analyzed the possible underlying molecular mechanism. Chrysotile asbestos induced autophagy in A549 cells based on a series of biochemical and microscopic autophagy markers. We observed that asbestos increased expression of A549 cell microtubule-associated protein 1 light chain 3 (LC3-II), an autophagy marker, in conjunction with dephosphorylation of phospho-AKT, phospho-mTOR, and phospho-p70S6K. Notably, AKT1/AKT2 double-knockout murine embryonic fibroblasts (MEFs) had negligible asbestos-induced LC3-II expression, supporting a crucial role for AKT signaling. Chrysotile asbestos also led to the phosphorylation/activation of Jun N-terminal kinase (JNK) and p38 MAPK. Pharmacologic inhibition of JNK, but not p38 MAPK, dramatically inhibited the protein expression of LC3-II. Moreover, JNK2(-/-) MEFs but not JNK1(-/-) MEFs blocked LC3-II levels induced by chrysotile asbestos. In addition, N-acetylcysteine, an antioxidant, attenuated chrysotile asbestos-induced dephosphorylation of P-AKT and completely abolished phosphorylation/activation of JNK. Finally, we demonstrated that chrysotile asbestos-induced apoptosis was not affected by the presence of the autophagy inhibitor 3-methyladenine or autophagy-related gene 5 siRNA, indicating that the chrysotile asbestos-induced autophagy may be adaptive rather than prosurvival. Our findings demonstrate that AKT/mTOR and JNK2 signaling pathways are required for chrysotile asbestos-induced autophagy. These data provide a mechanistic basis for possible future clinical applications targeting these signaling pathways in the management of asbestos-induced lung disease.}, } @article {pmid24730341, year = {2013}, author = {Imenpour, H and Ivaldi, GP and Brianti, A and Pastorino, G and Biggi, S and Auriati, L and Simonassi, C}, title = {Synchronous occurrence of pulmonary adenocarcinoma and pleural diffuse malignant mesothelioma.}, journal = {Pathologica}, volume = {105}, number = {6}, pages = {353-356}, pmid = {24730341}, issn = {0031-2983}, mesh = {Adenocarcinoma/*pathology ; Aged ; Humans ; Lung/*pathology ; Lung Neoplasms/*pathology ; Male ; Mesothelioma/*pathology ; *Neoplasms, Multiple Primary ; Pleura/*pathology ; Pleural Neoplasms/*pathology ; }, abstract = {We report a rare case of diffuse malignant pleural mesothelioma synchronous with a localized adenocarcinoma of lung in a 68-year old man with a suspicious history of asbestos exposure. Computed tomography revealed a sub-pleural mass in the lower lobe and an irregular dense area of medium lobe of right lung with thickening of pleura encasing the lung parenchyma and homolateral pleural effusion 1 cm thick. The patient underwent surgery and a right medium and lower lobectomy was performed. Upon frozen sections, intraoperative diagnosis was adenocarcinoma with a poorly differentiated component of lung infiltrating the pleura. The postoperative histological definitive diagnosis with an important contribution of immunostaining was synchronous pulmonary adenocarcinoma and pleural diffuse malignant epithelioid mesothelioma.}, } @article {pmid24716080, year = {2014}, author = {Algın, MC and Yaylak, F and Bayhan, Z and Aslan, F and Bayhan, NA}, title = {Malignant peritoneal mesothelioma: clinicopathological characteristics of two cases.}, journal = {Case reports in surgery}, volume = {2014}, number = {}, pages = {748469}, pmid = {24716080}, issn = {2090-6900}, abstract = {Introduction. Peritoneal mesothelioma is a rare tumor, presenting difficulties in diagnosis and treatment. Peritoneum is the second most common area of the mesothelioma after pleura, and even synchronous pleural and peritoneal mesotheliomas are observed in 30-45% of all cases. The diagnosis may be difficult due to lack of specific symptoms and clinical findings. In addition, a delay in the diagnosis is not rare especially in the absence of previous asbestos exposure. Here we report two cases of malignant peritoneal mesotheliomas. The diagnostic and therapeutic approaches for these rare neoplasms are discussed. Case Presentation. The cases were two men (one aged 54 years old and the other 40 years old). Prolonged abdominal pain and swelling were the primary presentation symptoms and findings. The mesotheliomas were developed in the right upper quadrant of abdomen in both of the cases. Both cases were treated with surgical resection. Final diagnosis were possible with histological and immunohistochemical documentation of tumor characteristics, which were consistent with dictating a mesothelial origin. No history of asbestos exposure was reported. Conclusion. Peritoneal mesotheliomas are rare clinical entities. However, patients with prolonged abdominal pain and abdominal masses should be considered to have atypical pathologies such as peritoneal mesotheliomas.}, } @article {pmid24714749, year = {2014}, author = {Meniawy, TM and Creaney, J and Lake, RA and Nowak, AK}, title = {Response to comment on 'Existing prognostic models, but not neutrophil-to-lymphocyte ratio, are prognostic in malignant mesothelioma'.}, journal = {British journal of cancer}, volume = {111}, number = {12}, pages = {2377}, pmid = {24714749}, issn = {1532-1827}, mesh = {*Biomarkers, Tumor ; Female ; Humans ; Lung Neoplasms/*mortality ; Lymphocytes/*cytology ; Male ; Mesothelioma/*mortality ; Neutrophils/*cytology ; }, } @article {pmid24714747, year = {2014}, author = {Kao, SC and van Zandwijk, N and Clarke, S}, title = {Comment on 'Existing prognostic models, but not neutrophil-to-lymphocyte ratio, are prognostic in malignant mesothelioma'.}, journal = {British journal of cancer}, volume = {111}, number = {12}, pages = {2376}, pmid = {24714747}, issn = {1532-1827}, mesh = {*Biomarkers, Tumor ; Female ; Humans ; Lung Neoplasms/*mortality ; Lymphocytes/*cytology ; Male ; Mesothelioma/*mortality ; Neutrophils/*cytology ; }, } @article {pmid24706728, year = {2014}, author = {Lamote, K and Nackaerts, K and van Meerbeeck, JP}, title = {Strengths, weaknesses, and opportunities of diagnostic breathomics in pleural mesothelioma-a hypothesis.}, journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology}, volume = {23}, number = {6}, pages = {898-908}, doi = {10.1158/1055-9965.EPI-13-0737}, pmid = {24706728}, issn = {1538-7755}, mesh = {Breath Tests/methods ; Humans ; Lung Neoplasms/*diagnosis/metabolism ; Mesothelioma/*diagnosis/metabolism ; Mesothelioma, Malignant ; Prognosis ; }, abstract = {Past and present asbestos use will reflect in increasing numbers of mesothelioma cases in the next decades, diagnosed at a late stage and with a dismal prognosis. This stresses the need for early detection tools, which could improve patients' survival. Recently, breath analysis as a noninvasive and fast diagnostic tool has found its way into biomedical research. High-throughput breathomics uses spectrometric, chromatographic, and sensor techniques to diagnose asbestos-related pulmonary diseases based upon volatile organic compounds (VOC) in breath. This article reviews the state-of-the-art available breath analyzing techniques and provides the insight in the current use of VOCs as early diagnostic or prognostic biomarkers of mesothelioma to stimulate further research in this field. Cancer Epidemiol Biomarkers Prev; 23(6); 898-908. ©2014 AACR.}, } @article {pmid24684899, year = {2014}, author = {Ascoli, V and Romeo, E and Carnovale Scalzo, C and Cozzi, I and Ancona, L and Cavariani, F and Balestri, A and Gasperini, L and Forastiere, F}, title = {Familial malignant mesothelioma: a population-based study in central Italy (1980-2012).}, journal = {Cancer epidemiology}, volume = {38}, number = {3}, pages = {273-278}, doi = {10.1016/j.canep.2014.02.014}, pmid = {24684899}, issn = {1877-783X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/poisoning ; Environmental Exposure/adverse effects/statistics & numerical data ; Female ; Genetic Predisposition to Disease ; Humans ; Italy/epidemiology ; Lung Neoplasms/*epidemiology/etiology/genetics ; Male ; Mesothelioma/*epidemiology/etiology/genetics ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/adverse effects/statistics & numerical data ; }, abstract = {Malignant mesothelioma is a sporadic cancer linked to asbestos exposure. Its occurrence among blood relatives (familial mesothelioma) may point to genetic susceptibility or shared exposures. The burden of the familial disease is unknown. The aims of the study were to assess at population level the proportion of familial mesotheliomas among all mesotheliomas and to investigate the family history of cancer among relatives of mesothelioma cases. We actively searched familial clusters based on a mesothelioma registry from central Italy (5.5 million people, 10% of the Italian population) of the National Mesothelioma Register network (ReNaM) as well as a pathology-based archive. Among 997 incident mesotheliomas recorded in a 32-year-period (1980-2012), we detected 13 clusters and 34 familial cases, accounting for 3.4% of all mesotheliomas. The most common clusters where those with affected siblings and unaffected parents. Asbestos exposure was occupational (n=7 clusters), household (n=2), environmental (n=1), or not attributable for insufficient information (n=3). There were 25 additional cancers in nine families. Some were cancer sites for which there is sufficient evidence (lung and larynx) or limited evidence (stomach and colon) of causal association with asbestos. The results suggest potential genetic recessive effects in mesothelioma that interact with asbestos exposure, but it is not possible to estimate the specific proportion attributable to each of these components.}, } @article {pmid24675492, year = {2014}, author = {Komurcuoglu, B and Cirak, AK and Kirakli, SC and Polat, G and Yucel, N and Usluer, O and Erer, O and Balci, G and Gayaf, M and Guldaval, F and Aktogu, S and Guclu, S and Ozsoz, A and Halilcolar, H}, title = {Prognostic factors affecting survival in malignant pleural mesothelioma: analysis of 125 subjects.}, journal = {Tumori}, volume = {100}, number = {1}, pages = {55-59}, doi = {10.1700/1430.15816}, pmid = {24675492}, issn = {2038-2529}, mesh = {Age Factors ; Aged ; Asbestos/toxicity ; Environmental Exposure/adverse effects ; Female ; Humans ; Kaplan-Meier Estimate ; Lung Neoplasms/blood/*mortality/*pathology/therapy ; Lymphatic Metastasis ; Male ; Mesothelioma/blood/*mortality/*pathology/therapy ; Mesothelioma, Malignant ; Middle Aged ; Neoplasm Staging ; Pleural Neoplasms/blood/*mortality/*pathology/therapy ; Prognosis ; Retrospective Studies ; Risk Factors ; Sex Factors ; Smoking/adverse effects ; Turkey/epidemiology ; }, abstract = {AIM OF THE STUDY: Determining the pre-treatment prognostic factors in malignant pleural mesothelioma is important in terms of estimating the course of the disease and selecting patients who are candidate for multimodal therapy. The aim of the study was to determine the prognostic factors affecting survival in patients with malignant pleural mesothelioma.

STUDY DESIGN: One hundred and twenty-five patients who had been diagnosed histologically as having malignant pleural mesothelioma over the past 5 years were evaluated retrospectively. Relationships of survival of the patients with their age, gender, exposure to asbestos, smoking history, platelet, hemoglobin, leukocyte (WBC) and serum LDH values, histology, performance score and stage of disease were examined.

RESULTS: Advanced clinical stage, N2 nodal involvement and the presence of distant metastasis were found to be related to survival. Sarcomatous histology was found to be a poor prognostic factor independently of other factors.

CONCLUSIONS: We showed that histological subtype and stage of disease were the most important parameters in planning the treatment, especially in determining the patients who were candidate for multimodal treatment and in estimating the prognosis.}, } @article {pmid24675242, year = {2014}, author = {Robella, M and Vaira, M and Mellano, A and Marsanic, P and Cinquegrana, A and Borsano, A and Barbera, M and Caneparo, A and Siatis, D and Sottile, A and De Simone, M}, title = {Treatment of diffuse malignant peritoneal mesothelioma (DMPM) by cytoreductive surgery and HIPEC.}, journal = {Minerva chirurgica}, volume = {69}, number = {1}, pages = {9-15}, pmid = {24675242}, issn = {0026-4733}, mesh = {Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage/*therapeutic use ; Biomarkers, Tumor/analysis ; Chemotherapy, Adjuvant ; Cisplatin/administration & dosage ; Combined Modality Therapy ; Doxorubicin/administration & dosage ; Female ; Humans ; Hyperthermia, Induced ; Infusions, Parenteral ; Kaplan-Meier Estimate ; Ki-67 Antigen/analysis ; Laparoscopy ; *Laparotomy ; Lung Neoplasms/chemistry/diagnosis/drug therapy/*surgery ; Male ; Mesothelioma/chemistry/diagnosis/drug therapy/*surgery ; Mesothelioma, Malignant ; Middle Aged ; Patient Selection ; Peritoneal Neoplasms/chemistry/diagnosis/drug therapy/*surgery ; Preoperative Care ; Treatment Outcome ; Young Adult ; }, abstract = {AIM: Diffuse malignant peritoneal mesothelioma (DMPM) is a rare and locally aggressive tumor with poor prognosis, related in most cases to asbestos exposure. It is increasing in frequency, but currently no standard therapy is available. The biology of this disease is still poorly understood. Several highly specialized centers have recently reported improved survival by means of an innovative local-regional approach. The purpose of this article is to evaluate the survival benefit and the morbidity rate of patients affected by DMPM treated at our institution by cytoreductive surgery (CRS) associated with hyperthermic intraperitoneal perioperative chemotherapy (HIPEC).

METHODS: This study includes 42 patients affected by DMPM treated by an uniform approach consisting of cytoreductive surgery associated with HIPEC using cisplatin and doxorubicin. The primary end point was overall survival and morbidity rate. The secondary end point was evaluation of prognostic variables for overall survival.

RESULTS: The median follow-up period was 72 months (range 1-235 months). Thirty-five patients (83.3%) presented epithelial tumors and 7 were affected by multicystic mesothelioma. The mean peritoneal cancer index (PCI) was 13. Thirty-eight patients (90.4%) had complete cytoreduction (CC-0/1). The overall morbidity rate was 35.7% associated to a perioperative mortality of 7.1%. Median overall survival rate was 65 months with a 1- and 5-year survival rates of 63% and 44%, respectively.

CONCLUSION: The treatment of DMPM by CRS+HIPEC in selected patients is a feasible technique that allows to achieve encouraging results in terms of overall survival rate, with an acceptable morbidity rate. Further investigations are needed to clarify the role and the timing of this promising technique.}, } @article {pmid24658968, year = {2014}, author = {Schonfeld, SJ and McCormack, V and Rutherford, MJ and Schüz, J}, title = {Regional variations in German mesothelioma mortality rates: 2000–2010.}, journal = {Cancer causes & control : CCC}, volume = {25}, number = {5}, pages = {615-624}, doi = {10.1007/s10552-014-0368-4}, pmid = {24658968}, issn = {1573-7225}, support = {13275/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/poisoning ; Cohort Studies ; Female ; Germany/epidemiology ; Germany, East/epidemiology ; Germany, West/epidemiology ; Humans ; Male ; Mesothelioma/*mortality ; Middle Aged ; }, abstract = {PURPOSE: Germany has one of the highest age-adjusted mesothelioma mortality rates worldwide. As mesothelioma occurs ≥ 30 years after asbestos exposure, contemporary rates likely reflect exposures in the 1960-1970s. During this period, political division between West and East Germany led to differences regarding the import and consumption of asbestos. It is unclear whether mesothelioma rates also differ between these formerly separate countries which are now served by similar health and mortality reporting systems, thereby facilitating regional comparisons.

METHODS: We examined regional, temporal, and sex variations in mesothelioma mortality rates in Germany in 2000-2010, collapsing the federal states into West Germany, East Germany, and Berlin. We calculated truncated (≥ 40 years) age-standardized mesothelioma mortality rates (ASRs(40+)) per 100,000 person-years, estimated sex-stratified mortality rate ratios (MRRs) (95 % confidence intervals (CIs)), adjusted for age and calendar year from Poisson models, and fitted age-period-cohort models.

RESULTS: There were 12,854 mesothelioma deaths at ages ≥ 40 years in Germany during 2000-2010. ASRs(40+) were higher in West (males 4.4; females 0.8) than East (males 1.7; females 0.6) Germany. MRRs for West versus East Germany were 2.68 (95 % CI 2.48-2.88) among males and 1.42 (95 % CI 1.27-1.59) among females. In both regions, mortality rates increased for birth cohorts until the mid 1940s and subsequently declined. The country's peak mesothelioma burden is predicted to occur by 2020.

CONCLUSIONS: Geographical differences in mesothelioma mortality rates are consistent with heterogeneous historical asbestos exposures. Differences may exist for other asbestos-related cancers and should be investigated in analytic studies with individual asbestos exposure information.}, } @article {pmid24654472, year = {2014}, author = {Okuda, T and Ogino, Y and Yamashita, S and Ishii, H and Kin, S and Nagata, A and Otsubo, M and Kataoka, H and Kitawaki, J}, title = {Diagnostic laparoscopy identifies a peritoneal adenomatoid-like mesothelioma masquerading as ovarian cancer: a case report.}, journal = {European journal of gynaecological oncology}, volume = {35}, number = {1}, pages = {91-94}, pmid = {24654472}, issn = {0392-2936}, mesh = {Adenomatoid Tumor/diagnosis/pathology/surgery ; Diagnosis, Differential ; Female ; Humans ; Laparoscopy ; Mesothelioma/diagnosis/pathology/*surgery ; Middle Aged ; Ovarian Neoplasms/diagnosis/pathology/surgery ; Peritoneal Neoplasms/diagnosis/pathology/surgery ; }, abstract = {The authors report a rare case of peritoneal adenomatoid mesothelioma in a woman with no history of asbestos exposure. A 61-year-old woman was originally suspected of having a bilateral ovarian tumor based on chest radiography and magnetic resonance imaging (MRI). Upon referral to our hospital, the presence of two solid masses was confirmed by enhanced MRI and 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (18F-FDG-PET/CT). Physical examination was normal, as were serum concentrations of the tumor markers CA 19-9, CA 125, and CEA. Laparoscopic surgery showed a right ovarian tumor and laparoscopic right salpingo-oophorectomy and adhesiotomy were performed. Two months later, the patient underwent laparoscopic segmental resection of the sigmoid colon, with histological analysis identifying an adenomatoid-like tumor. The final diagnosis was peritoneal adenomatoid-like mesothelioma with invasion of the right ovary. This case report demonstrates that imaging techniques must be coupled with laparoscopic surgery for an accurate diagnosis of peritoneal mesothelioma.}, } @article {pmid24649303, year = {2014}, author = {Hirohashi, T and Igarashi, K and Abe, M and Maeda, M and Hino, O}, title = {Retrospective analysis of large-scale research screening of construction workers for the early diagnosis of mesothelioma.}, journal = {Molecular and clinical oncology}, volume = {2}, number = {1}, pages = {26-30}, pmid = {24649303}, issn = {2049-9450}, abstract = {The early diagnosis of mesothelioma, an aggressive malignant tumor, is considered to be important for prognosis. X-ray is commonly used for the assessment of a mass in a population exhibiting a risk factor. However, there are currently no available studies indicating that such an assessment may be used to achieve early diagnosis and improve the patient's outcome. We previously reported that N-ERC/mesothelin may be a useful blood tumor marker for mesothelioma. In order to investigate whether this tumor marker is useful for early diagnosis in a mass examination, in 2007 we initiated a 5-year large-scale screening of construction workers with a risk of asbestos exposure in Japan. Blood samples were collected annually and N-ERC/mesothelin levels were determined. Based on the results of those findings, along with medical history and related data, we screened the participants to identify a high-risk population. As a result, 62 subjects were identified among ~40,000 participants as the high-risk population. Two of these 62 participants subsequently developed mesothelioma, although the remaining participants have not yet developed mesothelioma. In conclusion, N-ERC/mesothelin may be useful as a blood tumor marker in the early diagnosis of mesothelioma in a mass examination. A future prospective study to confirm the findings of this research screening is currently under planning.}, } @article {pmid24649274, year = {2013}, author = {Fukuoka, K and Kuribayashi, K and Yamada, S and Tamura, K and Tabata, C and Nakano, T}, title = {Combined serum mesothelin and carcinoembryonic antigen measurement in the diagnosis of malignant mesothelioma.}, journal = {Molecular and clinical oncology}, volume = {1}, number = {6}, pages = {942-948}, pmid = {24649274}, issn = {2049-9450}, abstract = {Malignant mesothelioma (MM) is a highly aggressive tumor associated with asbestos exposure. The identification of a marker specific for MM may be of considerable value for the early detection of this tumor and may be used in particular to screen groups with a history of asbestos exposure. The aim of this study was to evaluate serum soluble mesothelin-related peptide (SMRP) levels as a diagnostic marker for MM and investigate whether its diagnostic value is enhanced by combination with other biomarkers. Serum SMRP levels were measured using a quantitative enzyme-linked immunosorbent assay in 96 patients with MM, 55 patients with lung cancer and 39 individuals with a history of asbestos exposure. Receiver operating characteristic curves were constructed for performance evaluation. Stepwise logistic regression analysis was used to select marker combinations (MCs). Serum SMRP levels in patients with MM were significantly higher compared to those in the other groups (P<0.001). The sensitivity of SMRP levels in diagnosing MM was 56% and its specificity for MM vs. lung cancer and individuals with asbestos exposure was 87 and 92%, respectively. The area under the curve (AUC) was 0.76 [95% confidence interval (CI): 0.68-0.83] for the differentiation between MM and lung cancer and 0.78 (95% CI: 0.71-0.86) for the differentiation between MM and individuals with asbestos exposure. For the MC of presence of effusion, SMRP and carcinoembryonic antigen (CEA) levels, the AUC for the differentiation between MM and lung cancer (0.92; 95% CI: 0.88-0.97) and the differentiation between MM and individuals with asbestos exposure (0.93; 95% CI: 0.87-1.0) was significantly higher compared to that for SMRP alone (P=0.0001 and 0.0058, respectively). While the specificity of this MC was comparable to SMRP alone, its sensitivity was ∼20% higher compared to that of SMRP alone. Therefore, combining SMRP and CEA improves the diagnostic performance of SMRP alone. A combination of serum biomarkers, including SMRP, may facilitate the non-invasive diagnosis of MM.}, } @article {pmid24645844, year = {2014}, author = {Kaya, H and Sezgı, C and Tanrıkulu, AC and Taylan, M and Abakay, O and Sen, HS and Abakay, A and Kucukoner, M and Kapan, M}, title = {Prognostic factors influencing survival in 35 patients with malignant peritoneal mesothelioma.}, journal = {Neoplasma}, volume = {61}, number = {4}, pages = {433-438}, doi = {10.4149/neo_2014_053}, pmid = {24645844}, issn = {0028-2685}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Environmental Exposure/adverse effects ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/etiology/*mortality/pathology ; Male ; Mesothelioma/etiology/*mortality/pathology ; Mesothelioma, Malignant ; Middle Aged ; Neoplasm Staging ; Peritoneal Neoplasms/etiology/*mortality/pathology ; Pleural Neoplasms/etiology/*mortality/pathology ; Prognosis ; Retrospective Studies ; Survival Rate ; }, abstract = {Malignant mesothelioma is a rare but highly lethal form of cancer that affects the serosal membranes. Malignant peritoneal mesothelioma (MPM) is the second most common form of malignant mesothelioma (pleural mesothelioma is the most common). The aim of this study was to evaluate prognostic factors influencing the survival of patients with MPM. A retrospective analysis was performed on 35 patients who were admitted to our hospital between March 2005 and July 2013. The patients' demographic and clinical data, laboratory results, radiological signs, Eastern Cooperative Oncology Group (ECOG) performance status (PS), and treatment outcomes were evaluated. The mean age of the 35 patients was 59.0±14.4 years, the mean survival time was 16.2±12.9 months, and the majority of the histopathological types of MPM were epithelial (68.6%). 82.9% of the patients had been exposed to asbestos, and the mean duration of exposure was 28.3±14.5 years. The most frequent symptoms were abdominal distention/pain, weight loss, dyspnea, and chest pain. The mean interval between the onset of symptoms and the diagnosis was 4.6±3.3 months. Platinum-based combination chemotherapy in combination with supportive care was used in the treatment of 68.6% of the patients, while supportive treatment alone was used in the others. Our results revealed that patients who were >60 years old (p=0.019), who were exposed to asbestos >20 years (p=0.033), who had an ECOG PS of 3 (p=0.000) were more likely to have a poor MPM prognosis.In conclusion, increased age, duration of environmental asbestos exposure and ECOG PS are important factors that influence the prognosis of MPM patients.}, } @article {pmid24630637, year = {2014}, author = {Galateau-Sallé, F and Gilg Soit Ilg, A and Le Stang, N and Brochard, P and Pairon, JC and Astoul, P and Frenay, C and Blaizot, G and Chamming's, S and Ducamp, S and Rousvoal, T and de Quillacq, A and Abonnet, V and Abdalsamad, I and Begueret, H and Brambilla, E and Capron, F and Copin, MC and Danel, C and de Lajartre, AY and Foulet-Roge, A and Garbe, L and Groussard, O and Giusiano, S and Hofman, V and Lantuejoul, S and Piquenot, JM and Rouquette, I and Sagan, C and Thivolet-Bejui, F and Vignaud, JM and Scherpereel, A and Jaurand, MC and Jean, D and Hainaut, P and Chérié-Challine, L and Goldberg, M and Luce, D and Imbernon, E}, title = {[The French mesothelioma network from 1998 to 2013].}, journal = {Annales de pathologie}, volume = {34}, number = {1}, pages = {51-63}, doi = {10.1016/j.annpat.2014.01.009}, pmid = {24630637}, issn = {0242-6498}, mesh = {France ; Humans ; *Mesothelioma/pathology ; Pathology, Clinical ; *Pleural Neoplasms/pathology ; Referral and Consultation ; Societies, Medical ; Time Factors ; }, abstract = {Mesothelioma is a rare disease less than 0.3% of cancers in France, very aggressive and resistant to the majority of conventional therapies. Asbestos exposure is nearly the only recognized cause of mesothelioma in men observed in 80% of case. In 1990, the projections based on mortality predicted a raise of incidence in mesothelioma for the next three decades. Nowadays, the diagnosis of this cancer is based on pathology, but the histological presentation frequently heterogeneous, is responsible for numerous pitfalls and major problems of early detection toward effective therapy. Facing such a diagnostic, epidemiological and medico-legal context, a national and international multidisciplinary network has been progressively set up in order to answer to epidemiological survey, translational or academic research questions. Moreover, in response to the action of the French Cancer Program (action 23.1) a network of pathologists was organized for expert pathological second opinion using a standardized procedure of certification for mesothelioma diagnosis. We describe the network organization and show the results during this last 15years period of time from 1998-2013. These results show the major impact on patient's management, and confirm the interest of this second opinion to provide accuracy of epidemiological data, quality of medico-legal acknowledgement and accuracy of clinical diagnostic for the benefit of patients. We also show the impact of these collaborative efforts for creating a high quality clinicobiological, epidemiological and therapeutic data collection for improvement of the knowledge of this dramatic disease.}, } @article {pmid24630634, year = {2014}, author = {Mery, É and Hommell-Fontaine, J and Capovilla, M and Chevallier, A and Bibeau, F and Croce, S and Dartigues, P and Kaci, R and Lang-Averous, G and Laverriere, MH and Leroux-Broussier, A and Poizat, F and Robin, N and Valmary-Degano, S and Verriele-Beurrier, V and Villeneuve, L and Isaac, S}, title = {[Peritoneal malignant mesothelioma: review and recent data].}, journal = {Annales de pathologie}, volume = {34}, number = {1}, pages = {26-33}, doi = {10.1016/j.annpat.2014.01.004}, pmid = {24630634}, issn = {0242-6498}, mesh = {Diagnosis, Differential ; Humans ; *Lung Neoplasms/pathology ; *Mesothelioma/pathology ; Mesothelioma, Malignant ; *Peritoneal Neoplasms/pathology ; }, abstract = {Peritoneal malignant mesothelioma is a rare tumor, less common than its pleural counterpart. It develops from the mesothelial cells overlying peritoneum and preferentially occurs in male, with an average age ranging from 47 to 60.5 years. Asbestos whose impact is less strong than in pleural mesothelioma, SV 40 virus, chronic peritonitis could be implicated as factors favoring the development of peritoneal mesothelioma. Clinical symptoms are not specific, and the imagery remains little or not contributive. The 2004 WHO classification recognizes 3 different types, which differ in terms of presentation and prognosis: diffuse epithelioid mesothelioma (the most common), sarcomatoid mesothelioma and biphasic mesothelioma. Many variants are described within these groups. Immunohistochemistry is mandatory to affirm or disprove peritoneal malignant mesothelioma diagnosis, based on a panel of antibodies divided in positive markers and negative markers. Indeed an accurate diagnosis is necessary to define a therapeutic strategy more and more frequently based on the combination of radical surgery and hyperthermic intra peritoneal chemotherapy. Such an approach significantly improves the prognosis of these aggressive diseases.}, } @article {pmid24620488, year = {2014}, author = {Reeve, P}, title = {Tackling asbestos- the hidden killer.}, journal = {Health estate}, volume = {68}, number = {2}, pages = {27-29}, pmid = {24620488}, mesh = {Asbestos/*adverse effects ; Asbestosis/complications/etiology/mortality/*prevention & control ; Health Facility Environment/legislation & jurisprudence/*standards ; Humans ; Lung Neoplasms/etiology/mortality/*prevention & control ; Maintenance and Engineering, Hospital/legislation & jurisprudence/methods/*standards ; Mesothelioma/etiology/mortality/*prevention & control ; Mesothelioma, Malignant ; Occupational Exposure/adverse effects/legislation & jurisprudence/*prevention & control ; Risk Assessment/methods ; United Kingdom/epidemiology ; }, } @article {pmid24615668, year = {2014}, author = {Kurz, S and Grohé, C}, title = {[Malignant pleural mesothelioma: new aspects of medical therapy].}, journal = {Pneumologie (Stuttgart, Germany)}, volume = {68}, number = {5}, pages = {329-335}, doi = {10.1055/s-0034-1365025}, pmid = {24615668}, issn = {1438-8790}, mesh = {Antibodies, Monoclonal/*therapeutic use ; Antineoplastic Agents/*therapeutic use ; Chemoradiotherapy/*trends ; Combined Modality Therapy/trends ; Humans ; Immunotherapy/*trends ; Lung Neoplasms/*therapy ; Mesothelioma/*therapy ; Mesothelioma, Malignant ; Pleural Neoplasms/*therapy ; }, abstract = {Malignant pleural mesothelioma, a typical long-term consequence of exposure to asbestos, represents a therapeutic challenge. In the early stages of the disease, trimodal therapy combining surgery, radiation and chemotherapy is used as standard care. In advanced stages, the combination of cisplatin and pemetrexed has been approved as first-line therapy, but there is a lack of randomised controlled drug trials for second-line treatment. Monotherapy with pemetrexed, vinorelbine or gemcitabine may provide some survival benefit compared to treatment aiming at symptom control only. Immunotherapy seems to be a promising new concept. The so-called frustrated phagocytosis, with continuing antigen presentation leading to persisting local inflammation and antigen tolerance, can be interrupted by blocking the T-cell surface protein CTLA-4. The monoclonal antibodies ipilimumab and tremelimumab that block CTLA-4 can stimulate immune response and thus increase the number of tumor-infiltrating lymphocytes. Clinical studies exploring this avenue of treatment are being awaited with great excitement.}, } @article {pmid24615665, year = {2014}, author = {Biesterfeld, S and Schramm, M and Schad, A and Pomjanski, N}, title = {[Pleural effusion cytology of asbestos-associated malignant mesothelioma and lung carcinoma in the diagnosis of occupational diseases by the statutory accident insurance funds].}, journal = {Pneumologie (Stuttgart, Germany)}, volume = {68}, number = {4}, pages = {270-276}, doi = {10.1055/s-0034-1365157}, pmid = {24615665}, issn = {1438-8790}, mesh = {Aged ; Aged, 80 and over ; Asbestosis/*complications/*pathology ; Humans ; Insurance, Accident ; Lung Neoplasms ; Male ; Mesothelioma/*complications/*pathology ; Occupational Diseases/complications/pathology ; Pleural Effusion/*etiology/*pathology ; }, abstract = {Pleural effusion often represents the first clinical symptom of lung carcinoma and malignant mesothelioma. As pleural punctation is performed quite early in the diagnostic procedure, effusion cytology frequently gives the first evidence about the presence of tumour cells and tumor histogenesis. In this study, we report on seven cases which were evaluated in our institution for the Employers' Liability Insurance Association, based solely on cytology findings.The mean age of the seven patients with a given long-term asbestos exposure during their working life was 81.7 years. On average eight smears per patient were investigated. In addition to routine cytology, immunocytochemistry, DNA image cytometry, AgNOR-analysis and fluorescence in situ hybridization were applied in a case-specific way. The results were interpreted against the clinical and occupational history of the respective patient.Definitive diagnosis could be made in six cases. In three of them, the diagnosis of malignant mesothelioma was made. Two cases were diagnosed as malignant effusion due to metastatic lung cancer. In one case, cells of high-grade Non-Hodgkin's lymphoma (NHL) were diagnosed and a malignant mesothelioma was excluded. In the last case, malignant mesothelioma could not be diagnosed unequivocally by cytology. In all seven cases, our interpretation was accepted by Employers' Liability Insurance Association. The five mesothelioma or lung cancer cases were accepted as asbestos-associated occupational disease, while the NHL case was rejected. In the last case, malignant mesothelioma was diagnosed later by autopsy, and the case was retroactively accepted as occupational disease.Cytology-based tumor diagnosis including adjuvant methods is a useful and reliable approach in cases of asbestos-associated tumours. Acceptance of occupational disease on the basis of cytological diagnoses even by the Employers' Liability Insurance Association helps avoid invasive pleural or lung biopsies in cases with an unequivocally positive effusion cytology of lung cancer or malignant mesothelioma.}, } @article {pmid24614240, year = {2014}, author = {Bayram, M and Bakan, ND}, title = {Environmental exposure to asbestos: from geology to mesothelioma.}, journal = {Current opinion in pulmonary medicine}, volume = {20}, number = {3}, pages = {301-307}, doi = {10.1097/MCP.0000000000000053}, pmid = {24614240}, issn = {1531-6971}, mesh = {Asbestos/*toxicity ; Carcinogens/*toxicity ; Environmental Exposure/*adverse effects ; Female ; Geology ; Humans ; Lung Neoplasms/*chemically induced/prevention & control ; Male ; Mesothelioma/*chemically induced/prevention & control ; Risk Factors ; Soil ; *Urbanization ; }, abstract = {PURPOSE OF REVIEW: This article aims to review the geological background of environmental asbestos exposure and the distribution of asbestos-related disease (ARD) in association with naturally occurring asbestos (NOA), and discusses the potential health risks associated with exposure to non-occupational asbestos.

RECENT FINDINGS: With the motion of continental and oceanic plates, in some parts of the world serpentinites in the lower layer of the oceanic plate move into the continental plate and form the so-called ophiolites. Ophiolites consist of soil and rocks containing serpentine-type asbestos. There is an increase in ARDs in regions close to ophiolites. Indoor exposure and outdoor exposure to NOA, outdoor exposure to industrial asbestos and mines, urbanization and construction works in NOA regions are the known sources and types of environmental asbestos exposure.

SUMMARY: Although there is an expectance of decline in ARDs caused by industrial exposure to asbestos, the environmental exposure to asbestos is still a challenge waiting to be overcome.}, } @article {pmid24605531, year = {2014}, author = {Kishimoto, T}, title = {[Asbestos-related diseases].}, journal = {Nihon rinsho. Japanese journal of clinical medicine}, volume = {72}, number = {2}, pages = {300-305}, pmid = {24605531}, issn = {0047-1852}, mesh = {*Asbestosis ; Humans ; Lung Neoplasms/etiology ; Pleurisy ; }, abstract = {Asbestosis shows peribronchiolar fibrosis with numerous asbestos bodies. Subpleural dots and curvilinear lines in HRCT are good indicators for the diagnosis of asbestosis. Asbestos-related lung cancer in Japanese Compensation System means lung cancer with asbestosis. Furthermore, pleural plaques and the content of asbestos bodies in the lung tissues with the term of occupational asbestos exposure are good indicators. Mesothelioma induced also by the low dense exposure to asbestos. For the definite diagnosis of mesothelioma, we need histological examination using biopsy and immunochemical staining for positive and negative markers. Benign asbestos pleurisy is diagnosed by cytological and biochemical examinations of pleural effusions and pleural biopsy. Diffuse pleural thickening depends on the extent of radiological findings and impairment of pulmonary function with occupational asbestos exposure.}, } @article {pmid24602395, year = {2014}, author = {Lang-Lazdunski, L}, title = {Surgery for malignant pleural mesothelioma: why, when and what?.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {84}, number = {2}, pages = {103-109}, doi = {10.1016/j.lungcan.2014.01.021}, pmid = {24602395}, issn = {1872-8332}, mesh = {Humans ; Mesothelioma/*surgery ; Palliative Care ; Pleural Neoplasms/*surgery ; Quality of Life ; Thoracic Surgical Procedures/methods ; }, abstract = {Malignant pleural mesothelioma is a fatal cancer developing in the pleural cavity, linked to asbestos exposure. Various therapies have been tried in the past 50 years including surgery, radiotherapy, chemotherapy, immunotherapy and more recently, targeted therapy. Radical surgery remains controversial in malignant pleural mesothelioma and two procedures have been offered in the past to obtain maximal cytoreduction: extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D). Despite growing evidence that EPP might be detrimental, many believe that radical surgery should still be part of multimodality therapy in patients with malignant pleural mesothelioma. Recent evidence suggests that P/D is well tolerated and produces low mortality and morbidity. The role of adjuvant intrapleural therapies remains to be determined and evaluated in large prospective trials. Pleurectomy/decortication does not jeopardize the chance of having chemotherapy, or chemoradiotherapy either. Many now believe that it should be the default procedure in multimodality regimens. However, this remains to be proven in a large randomized trial. Palliative surgery still has an important role to play in mesothelioma, in establishing or refining diagnosis and in controlling symptoms and improving quality of life in many patients whose life expectancy is limited. Recent progress in molecular analyses and biomarkers should help with patient selection for surgery, immunotherapy and systemic therapies in the near future.}, } @article {pmid24598827, year = {2014}, author = {Jamal, S and Cheriyan, VT and Muthu, M and Munie, S and Levi, E and Ashour, AE and Pass, HI and Wali, A and Singh, M and Rishi, AK}, title = {CARP-1 functional mimetics are a novel class of small molecule inhibitors of malignant pleural mesothelioma cells.}, journal = {PloS one}, volume = {9}, number = {3}, pages = {e89146}, pmid = {24598827}, issn = {1932-6203}, mesh = {Amino Acid Sequence ; Antineoplastic Agents/*pharmacology ; Apoptosis ; Cell Line, Tumor ; Cell Movement ; Cell Survival/drug effects ; Cisplatin/pharmacology ; Drug Screening Assays, Antitumor ; Epithelial-Mesenchymal Transition ; Humans ; Lung Neoplasms ; Matrix Metalloproteinases/metabolism ; Membrane Glycoproteins/metabolism ; Mesothelioma ; Mesothelioma, Malignant ; Molecular Mimicry ; NF-kappa B/metabolism ; Neoplasm Invasiveness ; Phosphorylation ; Pleural Neoplasms ; Protein Processing, Post-Translational/drug effects ; Signal Transduction ; Spiro Compounds/*pharmacology ; Thiadiazoles/*pharmacology ; }, abstract = {Malignant pleural mesothelioma (MPM) is an asbestos-related thoracic malignancy that is characterized by late metastases, and resistance to therapeutic modalities. The toxic side-effects of MPM therapies often limit their clinical effectiveness, thus necessitating development of new agents to effectively treat and manage this disease in clinic. CARP-1 functional mimetics (CFMs) are a novel class of compounds that inhibit growth of diverse cancer cell types. Here we investigated MPM cell growth suppression by the CFMs and the molecular mechanisms involved. CFM-1, -4, and -5 inhibited MPM cell growth, in vitro, in part by stimulating apoptosis. Apoptosis by CFM-4 involved activation of pro-apoptotic stress-activated protein kinases (SAPKs) p38 and JNK, elevated CARP-1 expression, cleavage of PARP1, and loss of the oncogene c-myc as well as mitotic cyclin B1. Treatments of MPM cells with CFM-4 resulted in depletion of NF-κB signaling inhibitor ABIN1 and Inhibitory κB (IκB)α and β, while increasing expression of pro-apoptotic death receptor (DR) 4 protein. CFM-4 enhanced expression of serine-phosphorylated podoplanin and cleavage of vimetin. CFMs also attenuated biological properties of the MPM cells by blocking their abilities to migrate, form colonies in suspension, and invade through the matrix-coated membranes. Both podoplanin and vimentin regulate processes of cell motility and invasion, and their expression often correlates with metastatic disease, and poor prognosis. The fact that phosphorylation of serines in the cytoplasmic domain of podoplanin interferes with processes of cellular motility, CFM-4-dependent elevated phosphorylated podoplanin and cleavage of vimentin underscore a metastasis inhibitory property of these compounds, and suggest that CFMs and/or their future analogs have potential as anti-MPM agents.}, } @article {pmid24598051, year = {2014}, author = {Hiraku, Y and Sakai, K and Shibata, E and Kamijima, M and Hisanaga, N and Ma, N and Kawanishi, S and Murata, M}, title = {Formation of the nitrative DNA lesion 8-nitroguanine is associated with asbestos contents in human lung tissues: a pilot study.}, journal = {Journal of occupational health}, volume = {56}, number = {3}, pages = {186-196}, doi = {10.1539/joh.13-0231-oa}, pmid = {24598051}, issn = {1348-9585}, mesh = {Aged ; Asbestos/*analysis ; Biomarkers/chemistry ; Carcinogenesis ; Carcinogens/*analysis ; *DNA Damage ; Female ; Guanine/*analogs & derivatives/metabolism ; Humans ; Lung/*chemistry/metabolism/pathology ; Lung Neoplasms/pathology ; Male ; Mesothelioma/pathology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure ; Pilot Projects ; Staining and Labeling ; }, abstract = {OBJECTIVES: Asbestos causes lung cancer and malignant mesothelioma, and chronic inflammation is considered to participate in carcinogenesis. However, biomarkers to evaluate its carcinogenic risk have not been established. Reactive oxygen/nitrogen species are generated in biological systems under inflammatory conditions and may contribute to carcinogenesis by causing DNA damage. In this study, we examined the relationship between the formation of 8-nitroguanine (8-nitroG), a mutagenic DNA lesion formed during inflammation, and asbestos contents in human lung tissues.

METHODS: We obtained non-tumor lung tissues from patients with (n=15) and without mesothelioma (n=21). The expression of 8-nitroG and related molecules was examined by immunohistochemistry, and their staining intensities were semiquantitatively evaluated. Asbestos contents in lung tissues were analyzed by analytical transmission electron microscopy.

RESULTS: In subjects without mesothelioma, staining intensities of 8-nitroG and apurinic/apyrimidinic endonuclease 1 (APE1) were significantly correlated with total asbestos and amphibole contents (p<0.05), but not with chrysotile content. In mesothelioma patients, their staining intensities were not correlated with asbestos contents. The double immunofluorescence technique revealed that APE1 was expressed in 8-nitroG-positive cells, suggesting that abasic sites were formed possibly due to the removal of 8-nitroG. The staining intensities of 8-oxo-7,8-dihydro-2'-deoxyguanosine, an oxidative DNA lesion, and its repair enzyme 8-oxoguanine DNA-glycosylase were correlated with age (p<0.05), but not with asbestos contents in subjects without mesothelioma.

CONCLUSIONS: This is the first study to demonstrate that 8-nitroG formation is associated with asbestos contents in human lung tissues. This finding raises a possibility that 8-nitroG serves as a biomarker that can be used to evaluate asbestos exposure and carcinogenic risk.}, } @article {pmid24595274, year = {2014}, author = {Cheng, NC and van Zandwijk, N and Reid, G}, title = {Cilengitide inhibits attachment and invasion of malignant pleural mesothelioma cells through antagonism of integrins αvβ3 and αvβ5.}, journal = {PloS one}, volume = {9}, number = {3}, pages = {e90374}, pmid = {24595274}, issn = {1932-6203}, mesh = {Cell Adhesion/*drug effects ; Cell Line, Tumor ; Humans ; Integrin alphaVbeta3/*antagonists & inhibitors ; Mesothelioma/*pathology ; Neoplasm Invasiveness/*prevention & control ; Pleural Neoplasms/*pathology ; Receptors, Vitronectin/*antagonists & inhibitors ; Snake Venoms/*pharmacology ; }, abstract = {Malignant pleural mesothelioma (MPM) is an almost invariably fatal, asbestos-related malignancy arising from the mesothelial membrane lining the thoracic cavities. Despite some improvements in treatment, therapy is not considered curative and median survival following diagnosis is less than 1 year. Although still classed as a rare cancer, the incidence of MPM is increasing, and the limited progress in treating the disease makes the identification of new therapies a priority. As there is evidence for expression of the integrins αvβ3 and αvβ5 in MPM, there is a rationale for investigating the effects on MPM of cilengitide, a synthetic peptide inhibitor of integrin αv heterodimer with high specificity for αvβ3 and αvβ5. In mesothelial cells (MC) and 7 MPM cell lines, growth inhibition by cilengitide was associated with the expression level of its target integrins. Furthermore, cilengitide caused cell detachment and subsequent death of anoikis-sensitive cells. It also suppressed invasion of MPM cells in monolayer and three-dimensional cultures. Gene knockdown experiments indicated that these effects of cilengitide were, at least partly, due to antagonism of αvβ3 and αvβ5.}, } @article {pmid24592197, year = {2014}, author = {Sezgi, C and Taylan, M and Sen, HS and Evliyaoğlu, O and Kaya, H and Abakay, O and Abakay, A and Tanrıkulu, AC and Senyiğit, A}, title = {Oxidative status and acute phase reactants in patients with environmental asbestos exposure and mesothelioma.}, journal = {TheScientificWorldJournal}, volume = {2014}, number = {}, pages = {902748}, pmid = {24592197}, issn = {1537-744X}, mesh = {Acute-Phase Proteins/*analysis ; Adult ; Aged ; Asbestos/*toxicity ; Biomarkers, Tumor/*blood ; Case-Control Studies ; Copper/blood ; Cross-Sectional Studies ; Environmental Exposure/*adverse effects ; Female ; Humans ; Lung Neoplasms/*blood/chemically induced/diagnosis ; Male ; Mesothelioma/*blood/chemically induced/diagnosis ; Mesothelioma, Malignant ; Middle Aged ; Oxidants/blood ; *Oxidative Stress ; }, abstract = {BACKGROUND AND OBJECTIVES: The aim of this study was to investigate inflammatory indicators and oxidative status in patients with asbestos exposure with and without mesothelioma and to compare results with data from healthy subjects.

METHODS: Eighty people with exposure to environmental asbestos and without any disease, 46 mesothelioma patients, and a control group of 50 people without exposure to environmental asbestos were enrolled in this prospective study. Serum total oxidant level (TOL), total antioxidant capacity (TAC), and oxidative stress index (OSI), CRP, transferrin, ceruloplasmin, α-1 antitrypsin, ferritin, and copper levels were measured.

RESULTS: Mesothelioma group exhibited higher TOL, OSI, α1-antitrypsin, ferritin and copper levels as compared to the other groups (P < 0.001, P = 0.007, P < 0.0001, P < 0.001, and P < 0.001, resp.). Transferrin was lower in the mesothelioma group than in the other two groups (P < 0.001). The asbestos group had higher TOL, TAC, α1-antitrypsin, and transferrin levels (P < 0.001, P < 0.001, P < 0.001, and P < 0.001, resp.), as well as lower OSI and ferritin levels as compared to the control group (P < 0.001 and P < 0.001).

CONCLUSIONS: We believe that elevated acute phase reactants and oxidative stress markers (TOL and OSI) in the mesothelioma group can be used as predictive markers for the development of asbestos-related malignancy.}, } @article {pmid24577054, year = {2014}, author = {Mirabelli, D and Zugna, D}, title = {Comment on 'The latency period of mesothelioma among a cohort of British asbestos workers (1978-2005)'.}, journal = {British journal of cancer}, volume = {111}, number = {8}, pages = {1675}, pmid = {24577054}, issn = {1532-1827}, mesh = {Asbestos/*adverse effects ; Female ; Humans ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology ; Occupational Exposure/*adverse effects ; }, } @article {pmid24573972, year = {2014}, author = {Abakay, O and Tanrikulu, AC and Palanci, Y and Abakay, A}, title = {The value of inflammatory parameters in the prognosis of malignant mesothelioma.}, journal = {The Journal of international medical research}, volume = {42}, number = {2}, pages = {554-565}, doi = {10.1177/0300060513504163}, pmid = {24573972}, issn = {1473-2300}, mesh = {Asbestos/*adverse effects ; Environmental Exposure ; Female ; Humans ; Inflammation/*immunology ; Lung Neoplasms/*immunology/*mortality ; Lymphocyte Count ; Lymphocytes/immunology ; Male ; Mesothelioma/*immunology/*mortality ; Mesothelioma, Malignant ; Middle Aged ; Neutrophils/immunology ; Prognosis ; Retrospective Studies ; Survival Rate ; }, abstract = {OBJECTIVE: This study investigated the relationship between potential prognostic parameters that may be associated with increased inflammation and survival in patients with malignant mesothelioma (MM).

METHODS: This retrospective study assessed potential prognostic parameters measured at the time of MM diagnosis. Data on asbestos exposure, histopathological subtype of MM and laboratory parameters were collected.

RESULTS: In 155 patients with MM (90 male), mean survival time was 13.9 months. In univariate analysis, age ≥ 60 years and neutrophil-to-lymphocyte ratio (NLR) ≥ 3 were associated with significantly shortened median survival times. In multivariate analysis, nonepithelial subtype, red cell distribution width (RDW) ≥ 20% and NLR ≥ 3 were associated with significantly shortened median survival times. Mortality rate was increased 2.77-, 1.67- and 1.52-fold in patients with RDW ≥ 20%, NLR ≥ 3 and nonepithelial subtype, respectively. Nonepithelial subtype, white blood cell count ≥ 11 200 µl and platelet-to-lymphocyte ratio ≥ 300 at baseline were associated with a heightened NLR value.

CONCLUSIONS: The NLR and RDW were significant predictive factors for MM prognosis.}, } @article {pmid24567297, year = {2014}, author = {Sage, EK and Kolluri, KK and McNulty, K and Lourenco, Sda S and Kalber, TL and Ordidge, KL and Davies, D and Gary Lee, YC and Giangreco, A and Janes, SM}, title = {Systemic but not topical TRAIL-expressing mesenchymal stem cells reduce tumour growth in malignant mesothelioma.}, journal = {Thorax}, volume = {69}, number = {7}, pages = {638-647}, pmid = {24567297}, issn = {1468-3296}, support = {091730/WT_/Wellcome Trust/United Kingdom ; 260290/ERC_/European Research Council/International ; G1000355/MRC_/Medical Research Council/United Kingdom ; WT091730AIA/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Administration, Topical ; Animals ; Apoptosis/drug effects ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Female ; Flow Cytometry ; Humans ; Immunohistochemistry ; Infusions, Intravenous ; Lung Neoplasms/*metabolism/pathology ; Mesenchymal Stem Cell Transplantation/*methods ; Mesenchymal Stem Cells/metabolism/*physiology ; Mesothelioma/*metabolism/pathology ; Mesothelioma, Malignant ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Pleural Neoplasms/*metabolism/pathology ; TNF-Related Apoptosis-Inducing Ligand/metabolism/*pharmacology ; Transfection ; Tumor Burden/drug effects ; Tumor Cells, Cultured ; }, abstract = {Malignant pleural mesothelioma is a rare but devastating cancer of the pleural lining with no effective treatment. The tumour is often diffusely spread throughout the chest cavity, making surgical resection difficult, while systemic chemotherapy offers limited benefit. Bone marrow-derived mesenchymal stem cells (MSCs) home to and incorporate into tumour stroma, making them good candidates to deliver anticancer therapies. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a pro-apoptotic molecule that selectively induces apoptosis in cancer cells, leaving healthy cells unaffected. We hypothesised that human MSCs expressing TRAIL (MSCTRAIL) would home to an in vivo model of malignant pleural mesothelioma and reduce tumour growth. Human MSCs transduced with a lentiviral vector encoding TRAIL were shown in vitro to kill multiple malignant mesothelioma cell lines as predicted by sensitivity to recombinant TRAIL (rTRAIL). In vivo MSC homing was delineated using dual fluorescence and bioluminescent imaging, and we observed that higher levels of MSC engraftment occur after intravenous delivery compared with intrapleural delivery of MSCs. Finally, we show that intravenous delivery of MSCTRAIL results in a reduction in malignant pleural mesothelioma tumour growth in vivo via an increase in tumour cell apoptosis.}, } @article {pmid24564337, year = {2014}, author = {Robinson, C and Woo, S and Nowak, AK and Lake, RA}, title = {Dietary vitamin D supplementation does not reduce the incidence or severity of asbestos-induced mesothelioma in a mouse model.}, journal = {Nutrition and cancer}, volume = {66}, number = {3}, pages = {383-387}, doi = {10.1080/01635581.2013.878733}, pmid = {24564337}, issn = {1532-7914}, mesh = {Animals ; Asbestos/*toxicity ; Dietary Supplements ; Disease Models, Animal ; Mesothelioma/*chemically induced/diet therapy/epidemiology/mortality/*prevention & control ; Mice, Transgenic ; Vitamin D/blood/*pharmacology ; }, abstract = {Epidemiological studies suggest that vitamin and mineral intake is associated with cancer incidence. A prevention strategy based on diet or dietary supplementation could have enormous benefit, both directly, by preventing disease, and indirectly by alleviating fear in millions of people worldwide who have been exposed to asbestos. We have previously shown that dietary supplementation with the antioxidants vitamins A, E, and selenium does not affect overall survival nor the time to progression of asbestos-induced mesothelioma in MexTAg mice. Here we have extended our analysis to vitamin D. We compared survival of asbestos-exposed MexTAg mice provided with diets that were deficient or supplemented with 4500 IU/kg vitamin D (cholecalciferol). Survival of supplemented mice was significantly shorter than mice given a standard AIN93 diet containing 1000 IU/kg cholecalciferol (median survival was 29 and 32.5 weeks respectively). However, mice deficient in vitamin D had the same rate of mesothelioma development as control mice. Neither the latency time from asbestos exposure to diagnosis nor disease progression after diagnosis were significantly different between mice on these diets. We conclude that vitamin D is unlikely to moderate the incidence of disease in asbestos-exposed populations or to ameliorate the pathology in patients with established mesothelioma.}, } @article {pmid24562347, year = {2014}, author = {Truini, A and Coco, S and Alama, A and Genova, C and Sini, C and Dal Bello, MG and Barletta, G and Rijavec, E and Burrafato, G and Boccardo, F and Grossi, F}, title = {Role of microRNAs in malignant mesothelioma.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {71}, number = {15}, pages = {2865-2878}, pmid = {24562347}, issn = {1420-9071}, mesh = {Animals ; Biomarkers, Tumor/genetics ; *Gene Expression Regulation, Neoplastic ; Humans ; Lung/metabolism/pathology ; Lung Neoplasms/diagnosis/*genetics/therapy ; Mesothelioma/diagnosis/*genetics/therapy ; Mesothelioma, Malignant ; MicroRNAs/*genetics ; Oncogenes ; Prognosis ; }, abstract = {Malignant mesothelioma (MM) is an aggressive tumor, mainly derived from the pleura, which is predominantly associated with exposure to asbestos fibers. The prognosis of MM patients is particularly severe, with a median survival of approximately 9-12 months and latency between exposure and diagnosis ranging from 20-50 years (median 30 years). Emerging evidence has demonstrated that tumor aggressiveness is associated with genome and gene expression abnormalities; therefore, several studies have recently focused on the role of microRNAs (miRNAs) in MM tumorigenesis. miRNAs are small non-protein coding single-stranded RNAs (17-22 nucleotides) involved in numerous cellular processes that negatively regulate gene expression by modulating the expression of downstream target genes. miRNAs are often deregulated in cancer; in particular, the differential miRNA expression profiles of MM cells compared to unaffected mesothelial cells have suggested potential roles of miRNAs as either oncogenes or tumor suppressor genes in MM oncogenesis. In this review, the mechanism of MM carcinogenesis was evaluated through the analysis of the published miRNA expression data. The roles of miRNAs as diagnostic biomarkers and prognostic factors for potential therapeutic strategies will be presented and discussed.}, } @article {pmid24552091, year = {2014}, author = {Oddone, E and Ferrante, D and Cena, T and Tùnesi, S and Amendola, P and Magnani, C}, title = {[Asbestos cement factory in Broni (Pavia, Italy): a mortality study].}, journal = {La Medicina del lavoro}, volume = {105}, number = {1}, pages = {15-29}, pmid = {24552091}, issn = {0025-7818}, mesh = {Adult ; Asbestos/*adverse effects ; Cause of Death ; Cohort Studies ; Construction Materials/*adverse effects ; Female ; Humans ; Italy/epidemiology ; Male ; Mesothelioma/*mortality ; Middle Aged ; Occupational Diseases/*mortality ; Young Adult ; }, abstract = {BACKGROUND: To date, no study has reported cause-specific Standardized Mortality Ratios (SMR) for asbestos-cement workers at a manufacturing establishment in Broni (Pavia, Italy). This site is among those specifically targeted by Italian Law for reclamation (SIN - Site of National Interest for remediation).

OBJECTIVES: To provide cause-specific SMRs for asbestos-cement workers in the Broni (Pavia, Italy) factory, with particular regard to duration of employment and latency.

METHODS: Cause-specific SMRs for asbestos-cement workers (1296 workers hired since 1/1/1950 and with follow-up period 1/1/1970-30/06/2004: 1254 males and 42 females, 545 deaths, 523 males and 22 females) were calculated using the cause-specific mortality rates for the Lombardy Region. Similarly, for pleural and peritoneal mesothelioma and lung cancer among male workers, SMRs by duration of employment and latency were calculated.

RESULTS: Significantly increased SMRs were observed among male workers for pleural (SMR 17.99, 95% CI 11.75-26.36) and peritoneal (SMR 10.10, 95% CI 4.05-20.77) mesothelioma and lung cancer (SMR 1.26, 95% CI 1.02-1.55) and among female workers for pleural mesothelioma (SMR 68.90, 95% CI 8.33-248.90) and ovarian cancer (SMR 8.56, 95% CI 1.04-30.91). Only among male workers, was a significant risk trend observed for pleural mesothelioma by duration of employment and for lung cancer by latency. Significantly reduced SMRs were observed, among male workers for all causes of death, cardiovascular and respiratory diseases.

CONCLUSIONS: The results of this cohort study showed increased SMRs for pleural and peritoneal mesothelioma and lung cancer among male workers and for pleural mesothelioma and ovarian cancer among female workers. These results are consistent with the literature data.}, } @article {pmid24550969, year = {2013}, author = {Ahmed, I and Ahmed Tipu, S and Ishtiaq, S}, title = {Malignant mesothelioma.}, journal = {Pakistan journal of medical sciences}, volume = {29}, number = {6}, pages = {1433-1438}, pmid = {24550969}, issn = {1682-024X}, abstract = {UNLABELLED: Malignant Mesothelioma (MM) is a rare but rapidly fatal and aggressive tumor of the pleura and peritoneum with limited knowledge of its natural history. The incidence has increased in the past two decades but still it is a rare tumor. Etiology of all forms of mesothelioma is strongly associated with industrial pollutants, of which asbestos is the principal carcinogen. Mesothelioma is an insidious neoplasm arising from mesothelial surfaces i.e., pleura (65%-70%), peritoneum (30%), tunica vaginalis testis, and pericardium (1%-2%). The diagnosis of peritoneal and Pleural mesothelioma is often delayed, due to a long latent period between onset and symptoms and the common and nonspecific clinical presentation. The definite diagnosis can only be established by diagnostic laparoscopy or open surgery along with biopsy to obtain histological examination and immunocytochemical analysis. Different treatment options are available but Surgery can achieve a complete or incomplete resection and Radical resection is the preferred treatment. Chemotherapy has an important role in palliative treatment. Photodynamic therapy is also an option under trial. Patients who successfully underwent surgical resection had a considerably longer median survival as well as a significantly higher 5-year survival. Source of Data/Study Selection: The data were collected from case reports, cross-sectional studies, Open-label studies and phase -II trials between 1973-2012.

DATA EXTRACTION: Web sites and other online resources of American college of surgeons, Medline, NCBI and Medscape resource centers were used to extract data.

CONCLUSION: Malignant Mesothelioma (MM) is a rare but rapidly fatal and aggressive tumor with limited knowledge of its natural history. The diagnosis of peritoneal and Pleural mesothelioma is often delayed, so level of index of suspicion must be kept high.}, } @article {pmid24530353, year = {2014}, author = {Chen, T and Nie, H and Gao, X and Yang, J and Pu, J and Chen, Z and Cui, X and Wang, Y and Wang, H and Jia, G}, title = {Epithelial-mesenchymal transition involved in pulmonary fibrosis induced by multi-walled carbon nanotubes via TGF-beta/Smad signaling pathway.}, journal = {Toxicology letters}, volume = {226}, number = {2}, pages = {150-162}, doi = {10.1016/j.toxlet.2014.02.004}, pmid = {24530353}, issn = {1879-3169}, mesh = {Actins/metabolism ; Animals ; Antigens, CD ; Biomarkers/metabolism ; Cadherins/metabolism ; Cell Line, Tumor ; Collagen/metabolism ; Disease Models, Animal ; Epithelial Cells/metabolism/pathology ; *Epithelial-Mesenchymal Transition ; Fibroblasts/metabolism/pathology ; Humans ; Lung/*metabolism/pathology ; Male ; Mice ; Mice, Inbred C57BL ; *Nanotubes, Carbon ; Particle Size ; Phosphorylation ; Pulmonary Fibrosis/chemically induced/*metabolism/pathology ; *Signal Transduction ; Smad2 Protein/*metabolism ; Time Factors ; Transforming Growth Factor beta1/*metabolism ; }, abstract = {Multi-walled carbon nanotubes (MWCNT) are a typical nanomaterial with a wide spectrum of commercial applications. Inhalation exposure to MWCNT has been linked with lung fibrosis and mesothelioma-like lesions commonly seen with asbestos. In this study, we examined the pulmonary fibrosis response to different length of MWCNT including short MWCNT (S-MWCNT, length=350-700nm) and long MWCNT (L-MWCNT, length=5-15μm) and investigated whether the epithelial-mesenchymal transition (EMT) occurred during MWCNT-induced pulmonary fibrosis. C57Bl/6J male mice were intratracheally instilled with S-MWCNT or L-WCNT by a single dose of 60μg per mouse, and the progress of pulmonary fibrosis was evaluated at 7, 28 and 56 days post-exposure. The in vivo data showed that only L-MWCNT increased collagen deposition and pulmonary fibrosis significantly, and approximately 20% of pro-surfactant protein-C positive epithelial cells transdifferentiated to fibroblasts at 56 days, suggesting the occurrence of EMT. In order to understand the mechanism, we used human pulmonary epithelial cell line A549 to investigate the role of TGF-β/p-Smad2 signaling pathway in EMT. Our results showed that L-MWCNT downregulated E-cadherin and upregulated α-smooth muscle actin (α-SMA) protein expression in A549 cells. Taken together, both in vivo and in vitro study demonstrated that respiratory exposure to MWCNT induced length dependent pulmonary fibrosis and epithelial-derived fibroblasts via TGF-β/Smad pathway.}, } @article {pmid24518925, year = {2014}, author = {Zebedeo, CN and Davis, C and Peña, C and Ng, KW and Pfau, JC}, title = {Erionite induces production of autoantibodies and IL-17 in C57BL/6 mice.}, journal = {Toxicology and applied pharmacology}, volume = {275}, number = {3}, pages = {257-264}, pmid = {24518925}, issn = {1096-0333}, support = {P20 GM103408/GM/NIGMS NIH HHS/United States ; R15 ES021884/ES/NIEHS NIH HHS/United States ; R15 ES-21884/ES/NIEHS NIH HHS/United States ; P20GM103408/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Antibodies, Antinuclear/*blood ; Antigen-Antibody Complex/metabolism ; Asbestos, Amphibole/toxicity ; Asbestos, Serpentine/toxicity ; Autoimmunity/*drug effects ; Biomarkers/blood ; Cell Survival/drug effects ; Cells, Cultured ; Dose-Response Relationship, Drug ; Female ; Inhalation Exposure ; Interleukin-17/*blood ; Kidney/drug effects/immunology/metabolism ; Macrophages/drug effects/immunology/metabolism ; Mice ; Mice, Inbred C57BL ; Spleen/drug effects/immunology/metabolism ; Th1 Cells/drug effects/immunology/metabolism ; Th17 Cells/drug effects/immunology/metabolism ; Th2 Cells/drug effects/immunology/metabolism ; Time Factors ; Tumor Necrosis Factor-alpha/blood ; Up-Regulation ; Zeolites/*toxicity ; }, abstract = {BACKGROUND: Erionite has similar chemical and physical properties to amphibole asbestos, which induces autoantibodies in mice. Current exposures are occurring in North Dakota due to the use of erionite-contaminated gravel. While erionite is known to cause mesothelioma and other diseases associated with asbestos, there is little known about its effects on the immune system.

OBJECTIVES: We performed this study to determine whether erionite evokes autoimmune reactions in mice.

METHODS: Bone marrow derived macrophages (BMDM) were used to measure toxicity induced by erionite. Cytokine production by BMDM and splenocytes of C57BL/6 mice was examined by bead arrays and ELISA following exposure to erionite, amphiboles and chrysotile. Wild type C57BL/6 mice were exposed to saline, erionite, amphibole asbestos (Libby 6-Mix) or chrysotile through intratracheal instillations at equal mass (60μg/mouse). Seven months after exposure, sera were examined for anti-nuclear antibodies (ANA) and IL-17. Immunohistochemistry was used to detect immune complex deposition in the kidneys.

RESULTS: Erionite and tremolite caused increased cytokine production belonging to the TH17 profile including IL-17, IL-6, TGF-β, and TNF-α. The frequency of ANA was increased in mice treated with erionite or amphibole compared to saline-treated mice. IL-17 and TNF-α were elevated in the sera of mice treated with erionite. The frequency of immune complex deposition in the kidneys increased from 33% in saline-treated mice to 90% with erionite.

CONCLUSIONS: These data demonstrate that both erionite and amphibole asbestos induce autoimmune responses in mice, suggesting a potential for adverse effects in exposed communities.}, } @article {pmid24515241, year = {2014}, author = {Gorecka, M and Scott, J and Casey, R and Breen, D}, title = {The journey of mesothelioma: from postmortem to FNA.}, journal = {BMJ case reports}, volume = {2014}, number = {}, pages = {}, pmid = {24515241}, issn = {1757-790X}, mesh = {Aged ; Biopsy, Fine-Needle ; Diagnosis, Differential ; Fatal Outcome ; Humans ; Lung Neoplasms/*diagnosis/pathology ; Male ; Mesothelioma/*diagnosis/pathology ; Mesothelioma, Malignant ; Pleura/pathology ; Pleural Neoplasms/*diagnosis/pathology ; }, abstract = {A 73-year-old man, non-smoker presented with an 8-week history of left-sided chest pain and shortness of breath on exertion. He had no significant medical history. He worked in construction for 40 years, but denied definite asbestos exposure. His initial chest X-ray demonstrated a large left-sided pleural effusion. Subsequent CT thorax revealed circumferential thickening of the pleura with associated pleural plaques and calcification. A provisional diagnosis of mesothelioma was made. Initial ultrasound-guided thoracocentesis revealed a transudate with negative cytology. In addition, thoracoscopy and CT-guided pleural biopsy failed to obtain a definitive diagnosis. A surgical biopsy was planned, but at the time of admission, the patient developed unilateral neck swelling. Ultrasound-guided fine-needle aspiration (FNA) and core biopsies of the lymph node were diagnostic for pleural mesothelioma. Treatment with palliative chemotherapy was planned, but the patient's clinical status rapidly deteriorated and he passed away prior to the beginning of therapy.}, } @article {pmid24512074, year = {2014}, author = {Hwang, J and Ramachandran, G and Raynor, PC and Alexander, BH and Mandel, JH}, title = {The relationship between various exposure metrics for elongate mineral particles (EMP) in the taconite mining and processing industry.}, journal = {Journal of occupational and environmental hygiene}, volume = {11}, number = {9}, pages = {613-624}, doi = {10.1080/15459624.2014.890287}, pmid = {24512074}, issn = {1545-9632}, mesh = {Air Pollutants, Occupational/*analysis/chemistry ; Asbestos, Amphibole/analysis/chemistry ; Environmental Monitoring/instrumentation/*methods ; Humans ; Inhalation Exposure/*analysis ; *Iron ; Linear Models ; *Mining ; Minnesota ; Occupational Exposure/*analysis ; Particle Size ; Particulate Matter/*analysis/chemistry ; *Silicates ; }, abstract = {Different dimensions of elongate mineral particles (EMP) have been proposed as being relevant to respiratory health end-points such as mesothelioma and lung cancer. In this article, a methodology for converting personal EMP exposures measured using the National Institute for Occupational Safety and Health (NIOSH) 7400/7402 methods to exposures based on other size-based definitions has been proposed and illustrated. Area monitoring for EMP in the taconite mines in Minnesota's Mesabi Iron Range was conducted using a Micro Orifice Uniform Deposit Impactor (MOUDI) size-fractionating sampler. EMP on stages of the MOUDI were counted and sized according to each EMP definition using an indirect-transfer transmission electron microscopy (ISO Method 13794). EMP were identified using energy-dispersive x-ray and electron diffraction analysis. Conversion factors between the EMP counts based on different definitions were estimated using (1) a linear regression model across all locations and (2) a location-specific ratio of the count based on each EMP definition to the NIOSH 7400/7402 count. The highest fractions of EMP concentrations were found for EMP that were 1-3 μm in length and 0.2-0.5 μm in width. Therefore, the current standard NIOSH Method 7400, which only counts EMP >5 μm in length and ≥ 3 in aspect ratio, may underestimate amphibole EMP exposures. At the same time, there was a high degree of correlation between the exposures estimated according to the different size-based metrics. Therefore, the various dimensional definitions probably do not result in different dose-response relationships in epidemiological analyses. Given the high degree of correlation between the various metrics, a result consistent with prior research, a more reasonable metric might be the measurement of all EMP irrespective of size. [Supplementary materials are available for this article. Go to the publisher's online edition of Journal of Occupational and Environmental Hygiene for the following free supplemental resource: figures detailing EMP concentration.].}, } @article {pmid24510578, year = {2014}, author = {Nishikawa, S and Tanaka, A and Matsuda, A and Oida, K and Jang, H and Jung, K and Amagai, Y and Ahn, G and Okamoto, N and Ishizaka, S and Matsuda, H}, title = {A molecular targeting against nuclear factor-κB, as a chemotherapeutic approach for human malignant mesothelioma.}, journal = {Cancer medicine}, volume = {3}, number = {2}, pages = {416-425}, pmid = {24510578}, issn = {2045-7634}, mesh = {Animals ; Antineoplastic Agents/pharmacology ; Benzamides/pharmacology ; Cell Cycle Checkpoints/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Female ; Glutamates/pharmacology ; Guanine/analogs & derivatives/pharmacology ; Humans ; Lung Neoplasms/*drug therapy/metabolism/pathology ; Mesothelioma/*drug therapy/metabolism/pathology ; Mesothelioma, Malignant ; Mice ; Mice, Inbred BALB C ; Mice, SCID ; Molecular Targeted Therapy ; NF-kappa B/*antagonists & inhibitors/*metabolism ; Pemetrexed ; Xenograft Model Antitumor Assays ; }, abstract = {Chronic inflammation due to the absorption of asbestos is an important cause of mesothelioma. Although the increased prevalence of mesothelioma is a serious problem, the development of effective chemotherapeutic agents remains incomplete. As the nuclear factor-κB (NF-κB) pathway contributes to malignant transformation of various types of cells, we explored NF-κB activity in three different pathological types of malignant mesothelioma cells, and evaluated the therapeutic potential of a recently reported NF-κB inhibitor, IMD-0354. NF-κB was constantly activated in MSTO-211H, NCI-H28, and NCI-H2052 cells, and the proliferation of these cell lines was inhibited by IMD-0354. D-type cyclins were effectively suppressed in mixed tissue type MSTO-211H, leading to cell cycle arrest at sub G1 /G1 phase. IMD-0354 reduced cyclin D3 in both epithelial tissue type NCI-H28 and sarcomatoid tissue type NCI-H2052. In a sphere formation assay, IMD-0354 effectively decreased the number and diameter of MSTO-211H spheres. Preincubation of MSTO-211H cells with IMD-0354 delayed tumor formation in transplanted immunodeficient mice. Furthermore, administration of IMD-0354 markedly rescued the survival rate of mice that received intrathoracic injections of MSTO-211H cells. These results indicate that a targeted drug against NF-κB might have therapeutic efficacy in the treatment of human malignant mesothelioma.}, } @article {pmid24510539, year = {2014}, author = {Pukkala, E and Martinsen, JI and Weiderpass, E and Kjaerheim, K and Lynge, E and Tryggvadottir, L and Sparén, P and Demers, PA}, title = {Cancer incidence among firefighters: 45 years of follow-up in five Nordic countries.}, journal = {Occupational and environmental medicine}, volume = {71}, number = {6}, pages = {398-404}, doi = {10.1136/oemed-2013-101803}, pmid = {24510539}, issn = {1470-7926}, mesh = {Adenocarcinoma/epidemiology/etiology ; Adenocarcinoma of Lung ; Adult ; Age Factors ; Aged ; *Carcinogens ; Cohort Studies ; *Firefighters ; Follow-Up Studies ; Humans ; Incidence ; Lung Neoplasms/epidemiology/etiology ; Male ; Melanoma/epidemiology/etiology ; Middle Aged ; Multiple Myeloma/epidemiology/etiology ; Neoplasms/epidemiology/*etiology ; Occupational Diseases/epidemiology/*etiology ; Occupational Exposure/*adverse effects ; Prostatic Neoplasms/epidemiology/etiology ; Risk ; Scandinavian and Nordic Countries/epidemiology ; Skin Neoplasms/epidemiology/etiology ; Testicular Neoplasms/epidemiology/etiology ; Melanoma, Cutaneous Malignant ; }, abstract = {OBJECTIVES: Firefighters are potentially exposed to a wide range of known and suspected carcinogens through their work. The objectives of this study were to examine the patterns of cancer among Nordic firefighters, and to compare them with the results from previous studies.

METHODS: Data for this study were drawn from a linkage between the census data for 15 million people from the five Nordic countries and their cancer registries for the period 1961-2005. SIR analyses were conducted with the cancer incidence rates for the entire national study populations used as reference rates.

RESULTS: A total of 16 422 male firefighters were included in the final cohort. A moderate excess risk was seen for all cancer sites combined, (SIR=1.06, 95% CI 1.02 to 1.11). There were statistically significant excesses in the age category of 30-49 years in prostate cancer (SIR=2.59, 95% CI 1.34 to 4.52) and skin melanoma (SIR=1.62, 95% CI 1.14 to 2.23), while there was almost no excess in the older ages. By contrast, an increased risk, mainly in ages of 70 years and higher, was observed for non-melanoma skin cancer (SIR=1.40, 95% CI 1.10 to 1.76), multiple myeloma (SIR=1.69, 95% CI 1.08 to 2.51), adenocarcinoma of the lung (SIR=1.90, 95% CI 1.34 to 2.62), and mesothelioma (SIR=2.59, 95% CI 1.24 to 4.77). By contrast with earlier studies, the incidence of testicular cancer was decreased (SIR=0.51, 95% CI 0.23 to 0.98).

CONCLUSIONS: Some of these associations have been observed previously, and potential exposure to polycyclic aromatic hydrocarbons, asbestos and shift work involving disruption of circadian rhythms may partly explain these results.}, } @article {pmid24508707, year = {2014}, author = {Lacourt, A and Gramond, C and Rolland, P and Ducamp, S and Audignon, S and Astoul, P and Chamming's, S and Gilg Soit Ilg, A and Rinaldo, M and Raherison, C and Galateau-Salle, F and Imbernon, E and Pairon, JC and Goldberg, M and Brochard, P}, title = {Occupational and non-occupational attributable risk of asbestos exposure for malignant pleural mesothelioma.}, journal = {Thorax}, volume = {69}, number = {6}, pages = {532-539}, doi = {10.1136/thoraxjnl-2013-203744}, pmid = {24508707}, issn = {1468-3296}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Case-Control Studies ; Environmental Exposure ; Female ; France/epidemiology ; Humans ; Lung Neoplasms/epidemiology/*etiology ; Male ; Mesothelioma/epidemiology/*etiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Diseases/epidemiology/*etiology ; Occupational Exposure/*adverse effects ; Odds Ratio ; Pleural Neoplasms/epidemiology/*etiology ; Retrospective Studies ; Sex Factors ; Time Factors ; }, abstract = {OBJECTIVES: To estimate the proportion of pleural mesothelioma cases that can be attributed to asbestos exposure in France including non-occupational exposure.

METHODS: A population-based case-control study including 437 incident cases and 874 controls was conducted from 1998 to 2002. Occupational and non-occupational asbestos exposure was assessed retrospectively by two expert hygienists. ORs of pleural mesothelioma for asbestos-exposed subjects compared to non-exposed subjects, and population-attributable risk (ARp) of asbestos exposure were estimated using a conditional logistic regression.

RESULTS: A clear dose-response relationship was observed between occupational asbestos exposure and pleural mesothelioma (OR=4.0 (99% CI 1.9 to 8.3) for men exposed at less than 0.1 f/mL-year vs. 67.0 (99% CI 25.6 to 175.1) for men exposed at more than 10 f/mL-year). The occupational asbestos ARp was 83.1% (99% CI 74.5% to 91.7%) for men and 41.7% (99% CI 25.3% to 58.0%) for women. A higher risk of pleural mesothelioma was observed in subjects non-occupationally exposed to asbestos compared to those never exposed. The non-occupational asbestos ARp for these subjects was 20.0% (99% CI -33.5% to 73.5%) in men and 38.7% (99% CI 8.4% to 69.0%) in women. When considering all kinds of asbestos exposure, ARp was 87.3% (99% CI 78.9% to 95.7%) for men and 64.8% (99% CI 45.4% to 84.3%) for women.

CONCLUSIONS: Our study suggests that the overall ARp in women is largely driven by non-occupational asbestos exposure arguing for the strong impact of such exposure in pleural mesothelioma occurrence. Considering the difficulty in assessing domestic or environmental asbestos exposure, this could explain the observed difference in ARp between men and women.}, } @article {pmid24492694, year = {2014}, author = {Suzuki, S and Toyoshima, M and Nihashi, F and Tsukui, H and Baba, S and Sugimura, H and Suda, T}, title = {An autopsy case of malignant pleural mesothelioma associated with nephrotic syndrome.}, journal = {Internal medicine (Tokyo, Japan)}, volume = {53}, number = {3}, pages = {243-246}, doi = {10.2169/internalmedicine.53.1313}, pmid = {24492694}, issn = {1349-7235}, mesh = {Asbestos/*adverse effects ; Autopsy ; Humans ; Lung Neoplasms/*diagnosis/etiology ; Male ; Mesothelioma/*diagnosis/etiology ; Mesothelioma, Malignant ; Middle Aged ; Nephrotic Syndrome/*diagnosis/etiology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*diagnosis/etiology ; }, abstract = {A 64-year-old man who had been exposed to asbestos was referred to our hospital for a detailed examination of left pleural effusion. A laboratory examination of the urine and blood revealed nephrotic syndrome. A thoracoscopic examination did not yield a definitive diagnosis. Twenty months later, a left pleural tumor became apparent, and the patient died of respiratory failure and cachexia. An autopsy revealed epithelioid malignant pleural mesothelioma. The glomeruli appeared normal under light microscopy. A review of the English literature revealed only three reports of malignant mesothelioma associated with minimal-change nephrotic syndrome. The natural course of malignant mesothelioma with nephrotic syndrome has not been previously reported.}, } @article {pmid24491449, year = {2014}, author = {de Assis, LV and Locatelli, J and Isoldi, MC}, title = {The role of key genes and pathways involved in the tumorigenesis of Malignant Mesothelioma.}, journal = {Biochimica et biophysica acta}, volume = {1845}, number = {2}, pages = {232-247}, doi = {10.1016/j.bbcan.2014.01.008}, pmid = {24491449}, issn = {0006-3002}, mesh = {Asbestos/toxicity ; Carcinogenesis/*genetics ; Cell Transformation, Neoplastic/genetics/pathology ; Humans ; Lung Neoplasms/etiology/*genetics/pathology ; Mesothelioma/etiology/*genetics/pathology ; Mesothelioma, Malignant ; Phosphatidylinositol 3-Kinases/genetics/metabolism ; Signal Transduction/*genetics ; Simian virus 40/pathogenicity ; Zeolites/toxicity ; }, abstract = {Malignant Mesothelioma (MM) is a very aggressive cancer with low survival rates and often diagnosed at an advanced stage. Several players have been implicated in the development of this cancer, such as asbestos, erionite and the simian virus 40 (SV40). Here, we have reviewed the involvement of erionite, SV40, as well as, the role of several genes (p16(INK4a), p14(ARF), NF2, LATS2, SAV, CTNNB1 and among others), the pathways (RAS, PI3K, Wnt, BCL and Hippo), and their respective roles in the development of MM.}, } @article {pmid24480869, year = {2014}, author = {Ollier, M and Chamoux, A and Naughton, G and Pereira, B and Dutheil, F}, title = {Chest CT scan screening for lung cancer in asbestos occupational exposure: a systematic review and meta-analysis.}, journal = {Chest}, volume = {145}, number = {6}, pages = {1339-1346}, doi = {10.1378/chest.13-2181}, pmid = {24480869}, issn = {1931-3543}, mesh = {Aged ; Asbestos/*adverse effects ; Early Detection of Cancer/methods ; Female ; Humans ; Lung Neoplasms/*diagnostic imaging/etiology/mortality ; Male ; Mesothelioma/diagnostic imaging/etiology/mortality ; Middle Aged ; Occupational Exposure/*adverse effects ; Prevalence ; Smoking/adverse effects ; Survival Rate ; *Tomography, X-Ray Computed ; }, abstract = {OBJECTIVE: Lung cancer is the most frequent malignant asbestos-related pathology and remains the most fatal cancer of industrialized countries. In heavy smokers, early detection of lung cancer with chest CT scan leads to a 20% mortality reduction. However, the use of CT scan screening for early detection of lung cancer in asbestos-exposed workers requires further investigation. This study aimed to determine whether CT scan screening in asbestos-exposed workers is effective in detecting asymptomatic lung cancer using a systematic review and meta-analysis.

METHODS: We reviewed all cohort studies involving chest CT scan screening in former asbestos-exposed workers. The search strategy used the following keywords: "asbestos," "lung cancer," "screening," and "occupation*" or "work." Databases were PubMed, Cochrane Library, Science Direct, and Embase.

RESULTS: Seven studies matched our inclusion criteria. Baseline screening detected 49 asymptomatic lung cancers among 5,074 asbestos-exposed workers. Of the 49 reported lung cancers, at least 18 were in the earliest stage (stage I), accessible to complete removal surgery. The prevalence of all lung cancers detected by CT scan screening in asbestos-exposed workers was 1.1% (95% CI, 0.6%-1.8%).

CONCLUSIONS: CT scan screening in asbestos-exposed workers is effective in detecting asymptomatic lung cancer. Detection of lung cancer in asbestos-exposed workers using CT scanning is at least equal to the prevalence in heavy smokers (1%; 95% CI, 0.09%-1.1%) and also shared a similar proportion of stage I diagnoses. Screening asbestos-exposed workers could reduce mortality in proportions previously observed among heavy smokers and, thus, should not be neglected, particularly for individuals combining both exposures.}, } @article {pmid24472319, year = {2013}, author = {Kang, D and Myung, MS and Kim, YK and Kim, JE}, title = {Systematic Review of the Effects of Asbestos Exposure on the Risk of Cancer between Children and Adults.}, journal = {Annals of occupational and environmental medicine}, volume = {25}, number = {1}, pages = {10}, pmid = {24472319}, issn = {2052-4374}, abstract = {Children are considerably more susceptible to enviro006Emental hazards than adults. This study was conducted to investigate whether the first asbestos exposure in childhood increases the risk of asbestos-related cancer including mesothelioma and lung cancer. MEDLINE (PubMed), Embase, and Google Scholar were searched to find relevant studies published up to July 2012. Six studies reported the relationship between age, including age during childhood, at the first asbestos exposure and mesothelioma. Among them, 4 indicated that people exposed to asbestos in childhood have a higher risk of mesothelioma than those exposed in adulthood. Meanwhile, the other 2 studies showed that asbestos exposure later in life increases the risk of mesothelioma. The results of the 2 studies including non-occupational early childhood exposure report conflicting results. There were 3 studies regarding the relationship between age at first asbestos exposure and lung cancer. However, none of them reported an association between age at first asbestos exposure and the risk of lung cancer. All studies have limitations including small numbers of subjects, the validity of the standardized mortality ratio, and different age categories at first asbestos exposure. There are only a few studies on the harmful effects of asbestos in children in the literature. Therefore, the effect of asbestos exposure during childhood remains unclear and requires further study.}, } @article {pmid24457242, year = {2013}, author = {Cheng, YY and Kirschner, MB and Cheng, NC and Gattani, S and Klebe, S and Edelman, JJ and Vallely, MP and McCaughan, BC and Jin, HC and van Zandwijk, N and Reid, G}, title = {ZIC1 is silenced and has tumor suppressor function in malignant pleural mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {8}, number = {10}, pages = {1317-1328}, doi = {10.1097/JTO.0b013e3182a0840a}, pmid = {24457242}, issn = {1556-1380}, mesh = {Adult ; Aged ; Apoptosis ; Biomarkers, Tumor/genetics/metabolism ; Blotting, Western ; Cell Proliferation ; Chromatin Immunoprecipitation ; *DNA Methylation ; Female ; Fluorescent Antibody Technique ; Follow-Up Studies ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Humans ; Immunoenzyme Techniques ; Lung Neoplasms/*genetics/metabolism/mortality/pathology ; Male ; Mesothelioma/*genetics/metabolism/mortality/pathology ; Mesothelioma, Malignant ; MicroRNAs/*genetics ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Oligonucleotide Array Sequence Analysis ; Pleural Neoplasms/*genetics/metabolism/mortality/pathology ; Prognosis ; Promoter Regions, Genetic/genetics ; RNA, Messenger/genetics ; RNA, Small Interfering/genetics ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Survival Rate ; Transcription Factors/antagonists & inhibitors/genetics/*metabolism ; Tumor Cells, Cultured ; }, abstract = {INTRODUCTION: Epigenetic inactivation of tumor suppressor genes is involved in the development of malignant pleural mesothelioma (MPM). ZIC1, a potential tumor suppressor gene involved in regulating cell growth and apoptosis, was investigated in MPM cell lines and tumors.

METHODS: ZIC1 expression and promoter methylation were evaluated in MPM cell lines and tumor samples by quantitative polymerase chain reaction (PCR), Combined Bisulfite Restriction Analysis, and methylation-specific PCR. ZIC1 was reexpressed in cell lines and functional effects were assessed. miRNA expression was quantified by microarray and reverse transcription quantitative PCR. ZIC1 knockdown and miRNA inhibitors were used to study the relationship between ZIC1 and miRNA expression and confirmed by chromatin immunoprecipitation PCR.

RESULTS: ZIC1 expression was low in MPM cells, and was correlated with ZIC1 promoter methylation and reversed upon decitabine treatment. ZIC1 reexpression inhibited proliferation and invasion in MPM cells whereas knockdown enhanced the growth of MeT-5A. In MPM tumor samples ZIC1 expression was either low or undetectable, with promoter methylation observed in 16 of 24 cases. The overexpression of miR-23a and miR-27a was reduced by ZIC1 reexpression, with inhibitors of miR-23a or miR-27a reducing colony formation. miR-23a overexpression was also associated with shorter survival of MPM patients.

CONCLUSION: ZIC1 is down-regulated in MPM through promoter methylation and acts as a tumor suppressor through down-regulation of its direct targets miR-23a and miR-27a.}, } @article {pmid24455327, year = {2013}, author = {Humphrys, N and Downing, A and Evans, L and Sinclair, M}, title = {Traumatic implantation: a novel aetiology in the development of peritoneal mesothelioma.}, journal = {Case reports in emergency medicine}, volume = {2013}, number = {}, pages = {389130}, pmid = {24455327}, issn = {2090-648X}, abstract = {Peritoneal mesothelioma is a rare intra-abdominal malignancy. Its aetiology has been thought to be due to either inhalation or ingestion of asbestos particles. We present a case of peritoneal mesothelioma developing as a result of a novel third route and the inoculation of fibres into the peritoneal cavity by penetrating trauma and direct transport. This case report highlights the important long term consequences of penetrating abdominal trauma and the need for vigilance in undertaking peritoneal toilet.}, } @article {pmid24429116, year = {2013}, author = {Lim, JY and Wolf, AS and Flores, RM}, title = {The use of surgery in mesothelioma.}, journal = {The Lancet. Respiratory medicine}, volume = {1}, number = {3}, pages = {184-186}, doi = {10.1016/S2213-2600(13)70028-6}, pmid = {24429116}, issn = {2213-2600}, mesh = {*Asbestos ; Biopsy ; Chemoradiotherapy, Adjuvant ; Combined Modality Therapy ; Congresses as Topic ; Diagnosis, Differential ; Environmental Exposure/*adverse effects ; Female ; Humans ; Male ; *Mesothelioma/diagnosis/epidemiology/etiology/physiopathology/surgery ; Neoplasm Staging ; Patient Care Team ; *Pleura/pathology/surgery ; *Pleural Neoplasms/diagnosis/epidemiology/etiology/physiopathology/surgery ; Pneumonectomy/*methods ; Preoperative Care/*methods ; Prognosis ; Risk Factors ; Survival Analysis ; }, } @article {pmid24415579, year = {2014}, author = {Giusti, L and Da Valle, Y and Bonotti, A and Donadio, E and Ciregia, F and Ventroni, T and Foddis, R and Giannaccini, G and Guglielmi, G and Cristaudo, A and Lucacchini, A}, title = {Comparative proteomic analysis of malignant pleural mesothelioma evidences an altered expression of nuclear lamin and filament-related proteins.}, journal = {Proteomics. Clinical applications}, volume = {8}, number = {3-4}, pages = {258-268}, doi = {10.1002/prca.201300052}, pmid = {24415579}, issn = {1862-8354}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/toxicity ; Biomarkers, Tumor/*biosynthesis ; Female ; Gene Expression Regulation, Neoplastic ; Gene Regulatory Networks ; Humans ; Lamin Type B/biosynthesis ; Lung Neoplasms/chemically induced/*genetics/pathology ; Male ; Mesothelioma/chemically induced/*genetics/pathology ; Mesothelioma, Malignant ; Middle Aged ; Neoplasm Proteins/biosynthesis ; Pleural Neoplasms/chemically induced/*genetics/pathology ; *Proteomics ; }, abstract = {PURPOSE: Malignant mesothelioma is a neoplastic disease linked to asbestos exposure whose diagnosis is limited, so detection methods for an early diagnosis and treatment result essential. Here, we compared proteomic profiles of malignant pleural mesothelioma (MPM) and benign biopsies to search potential biomarkers useful in differential diagnosis.

EXPERIMENTAL DESIGN: Tissue biopsies were obtained from 53 patients who were subjected to a diagnostic thoracoscopy. 2DE/MS based approach was used for proteomic analysis and protein validation was carried out by Western blot analysis versus benign and lung carcinoma samples.

RESULTS: Among the proteins identified we confirmed known MPM biomarkers such as calretinin and suggested the new ones as prelamin A/C, desmin, vimentin, calretinin, fructose-bisphosphate aldolase A, myosin regulatory light chain 2, ventricular/cardiac muscle isoform, myosin light chain 3 and myosin light chain 6B. Ingenuity software was used to identify the biological processes to which these proteins belong and to construct a potential network.

Overall, our results suggest potential biomarkers that can be useful in occupational medicine for the early identification of the onset of disease in health surveillance of past asbestos-exposed workers, for monitoring the progress of disease and for assessing the response to treatment.}, } @article {pmid24409346, year = {2013}, author = {van Zandwijk, N}, title = {Clinical practice guidelines for malignant pleural mesothelioma.}, journal = {Journal of thoracic disease}, volume = {5}, number = {6}, pages = {724-725}, pmid = {24409346}, issn = {2072-1439}, } @article {pmid24401539, year = {2014}, author = {Filiberti, R and Marroni, P and Spigno, F and Merlo, DF and Mortara, V and Caruso, P and Cioè, A and Michelazzi, L and Bruzzone, A and Bobbio, B and Simonassi, C and Del Corso, L and Galli, R and Racchi, O and Dini, G and Linares, R and Mencoboni, M}, title = {Is soluble mesothelin-related protein an upfront predictive marker of pleural mesothelioma? A prospective study on Italian workers exposed to asbestos.}, journal = {Oncology}, volume = {86}, number = {1}, pages = {33-43}, doi = {10.1159/000355687}, pmid = {24401539}, issn = {1423-0232}, mesh = {Aged ; Asbestos/*adverse effects ; Biomarkers, Tumor/*blood ; Follow-Up Studies ; GPI-Linked Proteins/*blood ; Humans ; Lung Neoplasms/blood/*diagnosis ; Mesothelin ; Mesothelioma/blood/*diagnosis ; Mesothelioma, Malignant ; Middle Aged ; *Occupational Exposure ; Pleural Neoplasms/blood/*diagnosis ; Prospective Studies ; }, abstract = {OBJECTIVE: Soluble mesothelin-related peptide (SMRP) may be useful in the diagnosis and detection of early stage mesothelioma. We investigated the SMRP upfront predictive role for mesothelioma in asbestos-exposed workers.

METHODS: A total of 1,715 subjects underwent a first visit and were invited for a follow-up after 1 and 2 years, with a clinical examination and blood sampling. SMRP was measured by an ELISA assay.

RESULTS: Median SMRP at the first visit was 0.45 [interquartile range (IQR) i.e. 25th-75th percentile: 0.30-0.67 nmol/l]. In all, 1,676 subjects (97.8%) were followed up for a median period of 47.1 months. SMRP was measured at the first visit and at both follow-up visits in 1,536 subjects. At follow-up, 3 subjects were diagnosed with an epithelioid mesothelioma. In these cases, SMRP at the first visit ranged from 0.17 to 0.52 nmol/l. Malignant pleural mesothelioma was diagnosed 9-17 months after the last SMRP evaluation. No SMRP variation was observed during the follow-up. Other 61 miscellaneous cancers were diagnosed (median SMRP at first visit: 0.50 nmol/l, IQR: 0.34-0.71 nmol/l).

CONCLUSIONS: Our results did not support the usefulness of SMRP as an early marker for the detection of the disease for a time interval of 1 year.}, } @article {pmid24394956, year = {2014}, author = {Jennings, CJ and Walsh, PM and Deady, S and Harvey, BJ and Thomas, W}, title = {Malignant pleural mesothelioma incidence and survival in the Republic of Ireland 1994-2009.}, journal = {Cancer epidemiology}, volume = {38}, number = {1}, pages = {35-41}, doi = {10.1016/j.canep.2013.12.002}, pmid = {24394956}, issn = {1877-783X}, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Environmental Exposure ; Female ; Follow-Up Studies ; Humans ; Incidence ; Ireland/epidemiology ; Lung Neoplasms/*epidemiology/etiology/pathology ; Male ; Mesothelioma/*epidemiology/etiology/pathology ; Mesothelioma, Malignant ; Middle Aged ; Neoplasm Staging ; Pleural Neoplasms/*epidemiology/etiology/pathology ; Proportional Hazards Models ; Registries ; Risk Factors ; Survival Rate ; Young Adult ; }, abstract = {OBJECTIVE: Malignant pleural mesothelioma (MPM) is a rare malignancy associated with exposure to asbestos. The protracted latent period of MPM means that its incidence has continued to rise across Europe after the introduction of restrictions on asbestos use. In order to obtain a clearer indication of trends in the Republic of Ireland (ROI), incidence and survival were assessed based on all MPM cases reported since the establishment of the National Cancer Registry of Ireland (NCR).

METHODS: NCR recorded 337 MPM diagnoses in the ROI during 1994-2009. Survival was assessed for all cases diagnosed with adequate follow-up (n=330). Crude and European age-standardized incidence rates were calculated for all cases and for 4-year periods. A Cox model of observed (all-cause) survival was used to generate hazard ratios for the effect of: gender; age at diagnosis; diagnosis cohort; region of residence; histological type; and tumour stage. Single P-values for the variables indicated were calculated using either a stratified log-rank test or stratified trend test.

RESULTS: Over the study period the age-standardized MPM incidence in the ROI rose from 4.98cases per million (cpm) to 7.24cpm. The 1-year survival rate for all MPM cases was 29.6% (CI 24.7-34.6%). Excess mortality risk was associated with age at diagnosis (75-89 yrs vs. 55-64 yrs, HR 1.88, 95% CI 1.35-2.63, P<0.001) and tumour stage (III vs. I HR 1.57, 95% CI 1.00-2.48, P<0.05; IV vs. I HR 1.55, 95% CI 1.08-2.21, P<0.05). Age showed a significant survival trend (P<0.001) but tumour stage did not (P=0.150). There was significant heterogeneity between the survival of patients resident in different regions (P=0.027).

CONCLUSION: MPM incidence and mortality continued to rise in the ROI after the restrictions on asbestos use and the predictors of survival detected in this study are broadly consistent with those identified for other countries.}, } @article {pmid24387944, year = {2014}, author = {Charbotel, B and Fervers, B and Droz, JP}, title = {Occupational exposures in rare cancers: A critical review of the literature.}, journal = {Critical reviews in oncology/hematology}, volume = {90}, number = {2}, pages = {99-134}, doi = {10.1016/j.critrevonc.2013.12.004}, pmid = {24387944}, issn = {1879-0461}, mesh = {Humans ; Neoplasms/classification/*etiology ; *Occupational Exposure ; }, abstract = {The contribution of occupational exposures to rare cancers, which represent 22% of all cancers diagnosed annually in Europe, remains insufficiently considered. We conducted a comprehensive review of occupational risk factors in 67 rare cancers (annual incidence <6/100,000). An examination of relevant articles in PubMed (1960-2012) and the International Agency for Research on Cancer (IARC) monographs revealed that 26 cancer sites, such as mesothelioma, nasal, larynx, liver, ovarian cancer, bone sarcoma, and hematopoietic malignancies were consistently linked to occupational factors. Main exposures included asbestos, wood dust, metals/metalloids, formaldehyde, benzene, vinyl chloride, and radiation. There was inconsistent evidence regarding 22 rare malignancies. We did not identify relevant data for 19 rare cancers. Despite limitations of published evidence, our review provides useful information that can facilitate the identification of work-related factors that contribute to rare cancers. International collaborations, development of improved exposure assessment methods, and molecular approaches can improve future studies.}, } @article {pmid24375784, year = {2014}, author = {Silver, SR and Pinkerton, LE and Fleming, DA and Jones, JH and Allee, S and Luo, L and Bertke, SJ}, title = {Retrospective cohort study of a microelectronics and business machine facility.}, journal = {American journal of industrial medicine}, volume = {57}, number = {4}, pages = {412-424}, pmid = {24375784}, issn = {1097-0274}, support = {CC999999//Intramural CDC HHS/United States ; }, mesh = {Adult ; Asbestos/adverse effects ; Cause of Death ; Cohort Studies ; *Computers ; *Electronics ; Female ; Humans ; Incidence ; Lymphoma, Non-Hodgkin/mortality ; Male ; Mesothelioma/epidemiology ; Middle Aged ; Neoplasms/*epidemiology/mortality ; Nervous System Diseases/*epidemiology ; Occupational Diseases/*epidemiology/mortality ; Occupational Exposure/*statistics & numerical data ; Pleural Neoplasms/epidemiology ; Proportional Hazards Models ; Rectal Neoplasms/mortality ; Regression Analysis ; Retrospective Studies ; Testicular Neoplasms/epidemiology ; Tetrachloroethylene/*adverse effects ; }, abstract = {OBJECTIVES: We examined health outcomes among 34,494 workers employed at a microelectronics and business machine facility 1969-2001.

METHODS: Standardized mortality ratio (SMR) and standardized incidence ratios were used to evaluate health outcomes in the cohort and Cox regression modeling to evaluate relations between scores for occupational exposures and outcomes of a priori interest.

RESULTS: Just over 17% of the cohort (5,966 people) had died through 2009. All cause, all cancer, and many cause-specific SMRs showed statistically significant deficits. In hourly males, SMRs were significantly elevated for non-Hodgkin's lymphoma and rectal cancer. Salaried males had excess testicular cancer incidence. Pleural cancer and mesothelioma excesses were observed in workers hired before 1969, but no available records substantiate use of asbestos in manufacturing processes. A positive, statistically significant relation was observed between exposure scores for tetrachloroethylene and nervous system diseases.

CONCLUSIONS: Few significant exposure-outcome relations were observed, but risks from occupational exposures cannot be ruled out due to data limitations and the relative youth of the cohort.}, } @article {pmid24371224, year = {2014}, author = {Menges, CW and Kadariya, Y and Altomare, D and Talarchek, J and Neumann-Domer, E and Wu, Y and Xiao, GH and Shapiro, IM and Kolev, VN and Pachter, JA and Klein-Szanto, AJ and Testa, JR}, title = {Tumor suppressor alterations cooperate to drive aggressive mesotheliomas with enriched cancer stem cells via a p53-miR-34a-c-Met axis.}, journal = {Cancer research}, volume = {74}, number = {4}, pages = {1261-1271}, pmid = {24371224}, issn = {1538-7445}, support = {P01 CA114047/CA/NCI NIH HHS/United States ; R01 CA148805/CA/NCI NIH HHS/United States ; CA148805/CA/NCI NIH HHS/United States ; P30 CA006927/CA/NCI NIH HHS/United States ; CA-06927/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Asbestos ; *Cell Proliferation ; Cell Transformation, Neoplastic/*genetics ; Genes, Neurofibromatosis 2/physiology ; Genes, Tumor Suppressor/*physiology ; Genes, p53/physiology ; Mesothelioma/*genetics/pathology ; Mice ; Mice, SCID ; Mice, Transgenic ; MicroRNAs/physiology ; Mutation ; Neoplasm Invasiveness ; Neoplastic Stem Cells/pathology/*physiology ; Pleural Neoplasms/*genetics/pathology ; Proto-Oncogene Proteins c-met/physiology ; Signal Transduction/genetics ; Tumor Cells, Cultured ; }, abstract = {Malignant mesothelioma is a highly aggressive, asbestos-related cancer frequently marked by mutations of both NF2 and CDKN2A. We demonstrate that germline knockout of one allele of each of these genes causes accelerated onset and progression of asbestos-induced malignant mesothelioma compared with asbestos-exposed Nf2(+/-) or wild-type mice. Ascites from some Nf2(+/-);Cdkn2a(+/-) mice exhibited large tumor spheroids, and tail vein injections of malignant mesothelioma cells established from these mice, but not from Nf2(+/-) or wild-type mice, produced numerous tumors in the lung, suggesting increased metastatic potential of tumor cells from Nf2(+/-);Cdkn2a(+/-) mice. Intraperitoneal injections of malignant mesothelioma cells derived from Nf2(+/-);Cdkn2a(+/-) mice into severe combined immunodeficient mice produced tumors that penetrated the diaphragm and pleural cavity and harbored increased cancer stem cells (CSC). Malignant mesothelioma cells from Nf2(+/-);Cdkn2a(+/-) mice stained positively for CSC markers and formed CSC spheroids in vitro more efficiently than counterparts from wild-type mice. Moreover, tumor cells from Nf2(+/-);Cdkn2a(+/-) mice showed elevated c-Met expression/activation, which was partly dependent on p53-mediated regulation of miR-34a and required for tumor migration/invasiveness and maintenance of the CSC population. Collectively, these studies demonstrate in vivo that inactivation of Nf2 and Cdkn2a cooperate to drive the development of highly aggressive malignant mesotheliomas characterized by enhanced tumor spreading capability and the presence of a CSC population associated with p53/miR-34a-dependent activation of c-Met. These findings suggest that cooperativity between losses of Nf2 and Cdkn2a plays a fundamental role in driving the highly aggressive tumorigenic phenotype considered to be a hallmark of malignant mesothelioma.}, } @article {pmid24366282, year = {2014}, author = {Pillai, K and Ehteda, A and Akhter, J and Chua, TC and Morris, DL}, title = {Anticancer effect of bromelain with and without cisplatin or 5-FU on malignant peritoneal mesothelioma cells.}, journal = {Anti-cancer drugs}, volume = {25}, number = {2}, pages = {150-160}, doi = {10.1097/CAD.0000000000000039}, pmid = {24366282}, issn = {1473-5741}, mesh = {Antineoplastic Agents/*pharmacology ; Bromelains/*pharmacology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Cisplatin/*pharmacology ; Drug Interactions ; Fluorouracil/*pharmacology ; Humans ; Mesothelioma/*drug therapy ; Peritoneal Neoplasms/*drug therapy ; }, abstract = {Malignant peritoneal mesothelioma (MPM) is a rare neoplasm of the peritoneum, causally related to asbestos exposure. Nonspecific symptoms with a late diagnosis results in poor survival (<1 year). Treatment with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy has improved survival in some patients (median 3-5 years). Hence, new therapies are urgently needed. MUC1 is a glycosylation-dependent protein that confers tumours with invasiveness, metastasis and chemoresistance. Bromelain (cysteine proteinase) hydrolyses glycosidic bonds. Therefore, we investigated the antitumour effect of bromelain on MUC1-expressing MPM cell lines. MUC1 expressions in cells were assessed using immunofluorescent probes with cells grown on cover slips and western blot analysis on cell lysates. The cell lines were treated with various concentrations of bromelain and after 4 and 72 h, their viability was assessed using standard sulforhodamine assays. The cells were also treated with combinations of bromelain and cytotoxic drugs (cisplatin or 5-FU) and their viability was assessed at 72 h. Finally, with western blotting, the effects of bromelain on cellular survival proteins were investigated. PET cells expressed more MUC1 compared with YOU cells. The cell viability of both PET and YOU cells was adversely affected by bromelain, with PET cells being slightly resistant. The addition of bromelain increased the cytotoxicity of cisplatin significantly in both cell lines. However, 5-FU with bromelain did not show any significant increase in cytotoxicity. Bromelain-induced cell death is by apoptosis and autophagy. Bromelain has the potential of being developed as a therapeutic agent in MPM.}, } @article {pmid24365782, year = {2014}, author = {Indovina, P and Marcelli, E and Di Marzo, D and Casini, N and Forte, IM and Giorgi, F and Alfano, L and Pentimalli, F and Giordano, A}, title = {Abrogating G2/M checkpoint through WEE1 inhibition in combination with chemotherapy as a promising therapeutic approach for mesothelioma.}, journal = {Cancer biology & therapy}, volume = {15}, number = {4}, pages = {380-388}, pmid = {24365782}, issn = {1555-8576}, mesh = {Antineoplastic Agents/*pharmacology ; Apoptosis/drug effects ; Cell Cycle Proteins/*antagonists & inhibitors/metabolism ; Cell Line, Tumor ; Cisplatin/*pharmacology ; Drug Synergism ; *G2 Phase Cell Cycle Checkpoints ; Humans ; Lung Neoplasms/*drug therapy/pathology ; Mesothelioma/*drug therapy/pathology ; Mesothelioma, Malignant ; Nuclear Proteins/*antagonists & inhibitors/metabolism ; Protein-Tyrosine Kinases/*antagonists & inhibitors/metabolism ; Pyrazoles/*pharmacology ; Pyrimidines/*pharmacology ; Pyrimidinones ; }, abstract = {Malignant mesothelioma (MM) is a very aggressive asbestos-related neoplasm of the serous membranes, whose incidence is increasing worldwide. Although the introduction of new drug combinations, such as cisplatin plus pemetrexed/gemcitabine, has determined an improvement in the patient quality of life, MM remains a universally fatal disease. The observation that key G 1/S checkpoint regulators are often functionally inactivated in MM prompted us to test whether the use of G 2/M checkpoint inhibitors, able to sensitize G 1/S checkpoint-defective cancer cells to DNA-damaging agents, could be successful in MM. We treated six MM cell lines, representative of different histotypes (epithelioid, biphasic, and sarcomatoid), with cisplatin in combination with MK-1775, an inhibitor of the G 2/M checkpoint kinase WEE1. We observed that MK-1775 enhanced the cisplatin cytotoxic effect in all MM cell lines, except the sarcomatoid cell line, which is representative of the most aggressive histotype. As expected, the enhancement in cisplatin toxicity was accompanied by a decrease in the inactive phosphorylated form of cyclin-dependent kinase 1 (CDK1), a key substrate of WEE1, which is indicative of G 2/M checkpoint inactivation. Consistently, we also observed a decrease in G 2/M accumulation and an increase in mitotic entry of DNA-damaged cells and apoptosis, probably due to the loss of the cell ability to arrest cell cycle in response to DNA damage, irrespectively of p53 mutational status. Notably, this treatment did not increase cisplatin cytotoxicity on normal cells, thus suggesting a possible use of MK-1775 in combination with cisplatin for a safe and efficient treatment of epithelioid and biphasic MM.}, } @article {pmid24361865, year = {2014}, author = {Mundt, F and Johansson, HJ and Forshed, J and Arslan, S and Metintas, M and Dobra, K and Lehtiö, J and Hjerpe, A}, title = {Proteome screening of pleural effusions identifies galectin 1 as a diagnostic biomarker and highlights several prognostic biomarkers for malignant mesothelioma.}, journal = {Molecular & cellular proteomics : MCP}, volume = {13}, number = {3}, pages = {701-715}, pmid = {24361865}, issn = {1535-9484}, mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Computational Biology ; Discriminant Analysis ; Enzyme-Linked Immunosorbent Assay ; Female ; Galectin 1/*metabolism ; Humans ; Kaplan-Meier Estimate ; Least-Squares Analysis ; Lung Neoplasms/*diagnosis/*metabolism ; Male ; Mass Spectrometry ; Mesothelioma/*diagnosis/*metabolism ; Mesothelioma, Malignant ; Middle Aged ; Models, Biological ; Multivariate Analysis ; Pleural Effusion/*diagnosis/metabolism ; Principal Component Analysis ; Prognosis ; Proteome/*metabolism ; Proteomics/*methods ; ROC Curve ; Reproducibility of Results ; }, abstract = {Malignant mesothelioma is an aggressive asbestos-induced cancer, and affected patients have a median survival of approximately one year after diagnosis. It is often difficult to reach a conclusive diagnosis, and ancillary measurements of soluble biomarkers could increase diagnostic accuracy. Unfortunately, few soluble mesothelioma biomarkers are suitable for clinical application. Here we screened the effusion proteomes of mesothelioma and lung adenocarcinoma patients to identify novel soluble mesothelioma biomarkers. We performed quantitative mass-spectrometry-based proteomics using isobaric tags for quantification and used narrow-range immobilized pH gradient/high-resolution isoelectric focusing (pH 4-4.25) prior to analysis by means of nano liquid chromatography coupled to MS/MS. More than 1,300 proteins were identified in pleural effusions from patients with malignant mesothelioma (n = 6), lung adenocarcinoma (n = 6), or benign mesotheliosis (n = 7). Data are available via ProteomeXchange with identifier PXD000531. The identified proteins included a set of known mesothelioma markers and proteins that regulate hallmarks of cancer such as invasion, angiogenesis, and immune evasion, plus several new candidate proteins. Seven candidates (aldo-keto reductase 1B10, apolipoprotein C-I, galectin 1, myosin-VIIb, superoxide dismutase 2, tenascin C, and thrombospondin 1) were validated by enzyme-linked immunosorbent assays in a larger group of patients with mesothelioma (n = 37) or metastatic carcinomas (n = 25) and in effusions from patients with benign, reactive conditions (n = 16). Galectin 1 was identified as overexpressed in effusions from lung adenocarcinoma relative to mesothelioma and was validated as an excellent predictor for metastatic carcinomas against malignant mesothelioma. Galectin 1, aldo-keto reductase 1B10, and apolipoprotein C-I were all identified as potential prognostic biomarkers for malignant mesothelioma. This analysis of the effusion proteome furthers our understanding of malignant mesothelioma, identified galectin 1 as a potential diagnostic biomarker, and highlighted several possible prognostic biomarkers of this disease.}, } @article {pmid24354100, year = {2013}, author = {Voulgaridis, A and Apollonatou, V and Lykouras, D and Giannopoulos, A and Iliopoulou, M and Karkoulias, K and Kraniotis, P and Prokakis, C and Gkermpesi, M and Spiropoulos, K}, title = {Pleural mesothelioma in a young male patient.}, journal = {Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace}, volume = {79}, number = {2}, pages = {96-99}, doi = {10.4081/monaldi.2013.100}, pmid = {24354100}, issn = {1122-0643}, mesh = {Adult ; Asbestosis/*complications ; Bronchoscopy ; Diagnosis, Differential ; Humans ; Lung Neoplasms/*diagnosis/etiology/surgery ; Male ; Mesothelioma/*diagnosis/etiology/surgery ; Mesothelioma, Malignant ; Pleural Neoplasms/*diagnosis/etiology/surgery ; Pneumonectomy ; *Tomography, X-Ray Computed ; }, abstract = {We present the case of a 33-year-old male patient suffering from lymphocytic pleural effusion, as a result of pleural mesothelioma. Mesothelioma is a malignant tumor of the pleura that is mainly caused by chronic exposure to asbestos fibers and more than 40 years of exposure are needed to develop the disease. Early studies on the relationship of asbestos and mesothelioma were issued in the 1960s. Fibers migrate from the parenchyma of the lung to the visceral pleura. It is widely known that asbestos is an oncogenic factor which can cause damage to DNA. A chest x-ray may reveal pleural effusion with or without pleural thickening, whereas a chest CT may also reveal pleural thickening, uniform and/or lobular. Specific tests, such as immunohistochemical staining, are used in order to help differential diagnosis. Extrapleural pneumonectomy is used as a therapeutic option which involves removal of the lung as well as both the visceral and parietal pleura, the affected part of the pericardium and diaphragm. Surgery should be followed up by radiotherapy and chemotherapy. The surgery may lead to a mean survival rate of approximately 9-21 months. The case presented underlines that in the event of pleural effusion with a lymphocyte type physicians should consider the possibility of a pleural mesothelioma during differential diagnosis, even in relatively young patients.}, } @article {pmid24351898, year = {2014}, author = {Offermans, NS and Vermeulen, R and Burdorf, A and Goldbohm, RA and Kauppinen, T and Kromhout, H and van den Brandt, PA}, title = {Occupational asbestos exposure and risk of pleural mesothelioma, lung cancer, and laryngeal cancer in the prospective Netherlands cohort study.}, journal = {Journal of occupational and environmental medicine}, volume = {56}, number = {1}, pages = {6-19}, doi = {10.1097/JOM.0000000000000060}, pmid = {24351898}, issn = {1536-5948}, mesh = {Aged ; Asbestos/*toxicity ; Carcinoma/*epidemiology/etiology ; Follow-Up Studies ; Humans ; Laryngeal Neoplasms/*epidemiology/etiology ; Lung Neoplasms/*epidemiology/etiology ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Netherlands/epidemiology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*epidemiology/etiology ; Prospective Studies ; Risk Factors ; }, abstract = {OBJECTIVE: To study the association between occupational asbestos exposure and pleural mesothelioma, lung cancer, and laryngeal cancer, specifically addressing risk associated with the lower end of the exposure distribution, risk of cancer subtypes, and the interaction between asbestos and smoking.

METHODS: Using the Netherlands Cohort Study (n = 58,279 men, aged 55 to 69 years), asbestos exposure was estimated by linkage to job-exposure matrices. After 17.3 years of follow-up, 132 pleural mesothelioma, 2324 lung cancer, and 166 laryngeal cancer cases were available.

RESULTS: The multivariable-adjusted model showed overall positive associations between all levels of asbestos exposure and mesothelioma, lung cancer, and laryngeal cancer. Lung adenocarcinoma and glottis cancer showed only a positive association after prolonged higher asbestos exposure (hazard ratio per 10 years increment, 1.43 [95% confidence interval, 1.06 to 1.93] and 1.95 [95% confidence interval, 1.36 to 2.80], respectively). There was no statistically significant interaction between asbestos and smoking.

CONCLUSIONS: Asbestos levels encountered at the lower end of the exposure distribution may be associated with an increased risk of pleural mesothelioma, lung cancer, and laryngeal cancer.}, } @article {pmid24345738, year = {2014}, author = {Di Marzo, D and Forte, IM and Indovina, P and Di Gennaro, E and Rizzo, V and Giorgi, F and Mattioli, E and Iannuzzi, CA and Budillon, A and Giordano, A and Pentimalli, F}, title = {Pharmacological targeting of p53 through RITA is an effective antitumoral strategy for malignant pleural mesothelioma.}, journal = {Cell cycle (Georgetown, Tex.)}, volume = {13}, number = {4}, pages = {652-665}, doi = {10.4161/cc.27546}, pmid = {24345738}, issn = {1551-4005}, mesh = {Antineoplastic Agents/administration & dosage/pharmacology ; Apoptosis/*drug effects ; Cell Cycle/drug effects ; Cell Line, Tumor ; Cell Survival/drug effects ; Cisplatin/administration & dosage/pharmacology ; Drug Synergism ; Furans/*pharmacology ; Heterografts ; Humans ; Imidazoles/*pharmacology ; Lung Neoplasms/*metabolism/pathology ; Mesothelioma/*metabolism/pathology ; Mesothelioma, Malignant ; Mutation ; Piperazines/*pharmacology ; Pleural Neoplasms/*metabolism/pathology ; Tumor Suppressor Protein p53/*metabolism ; rho GTP-Binding Proteins/metabolism ; }, abstract = {Malignant mesothelioma, a very aggressive tumor associated to asbestos exposure, is expected to increase in incidence, and unfortunately, no curative modality exists. Reactivation of p53 is a new attractive antitumoral strategy. p53 is rarely mutated in mesothelioma, but it is inactivated in most tumors by the lack of p14(ARF). Here, we evaluated the feasibility of this approach in pleural mesothelioma by testing RITA and nutlin-3, two molecules able to restore p53 function through a different mechanism, on a panel of mesothelioma cell lines representing the epithelioid (NCI-H28, NCI-H2452, IST-MES 2), biphasic (MSTO-211H), and sarcomatoid (NCI-H2052) histotypes compared with the normal mesothelial HMC-hTERT. RITA triggered robust caspase-dependent apoptosis specifically in epithelioid and biphasic mesothelioma cell lines, both through wild-type and mutant p53, concomitant to p21 downregulation. Conversely, nutlin-3 induced a p21-dependent growth arrest, rather than apoptosis, and was slightly toxic on HMC-hTERT. Interestingly, we identified a previously undetected point mutation of p53 (p.Arg249Ser) in IST-MES 2, and showed that RITA is also able to reactivate this p53 mutant protein and its apoptotic function. RITA reduced tumor growth in a MSTO-211H-derived xenograft model of mesothelioma and synergized with cisplatin, which is the mainstay of treatment for this tumor. Our data indicate that reactivation of p53 and concomitant p21 downregulation effectively induce cell death in mesothelioma, a tumor characterized by a high intrinsic resistance to apoptosis. Altogether, our findings provide the preclinical framework supporting the use of p53-reactivating agents alone, or in combination regimens, to improve the outcome of patients with mesothelioma.}, } @article {pmid24340607, year = {2013}, author = {Pylev, LN and Vasil'eva, LA and Smirnova, OV and Vezentsev, AI and Gudkova, EA and Ingel', FI}, title = {[Carcinogenic and mutagenic activity of chrysotile, processed with iron chloride (III)].}, journal = {Gigiena i sanitariia}, volume = {}, number = {4}, pages = {76-80}, pmid = {24340607}, issn = {0016-9900}, mesh = {Animals ; Asbestos, Serpentine/chemistry/*toxicity ; Carcinogenicity Tests ; Chlorides/*chemistry ; Erythrocytes/drug effects/pathology ; Female ; Ferric Compounds/*chemistry ; Lung Neoplasms/*chemically induced ; Male ; Mesothelioma/*chemically induced ; Mesothelioma, Malignant ; Mice ; Mice, Inbred Strains ; Micronuclei, Chromosome-Defective/*chemically induced ; Micronucleus Tests ; Rats ; Rats, Wistar ; Surface Properties ; }, abstract = {This work is devoted to the study of the role of iron ions in the carcinogenic and mutagenic activity of chrysotile. For this aim natural chrysotile was treated with ferric chloride (III), washed, crushed and intratracheally introduced into Wistar rats. When administered to rats intact chrysotile induced mesotheliomas in 27,9 + 4,6% of cases, and chrysotile modified with ferric chloride - in 1,3 +/- 1,3%. Mutagenicity of the same samples was studied in the micronucleus test when administered intraperitoneally to mice Fl (CBA x S57Bl6). Polychromatic erythrocytes in the bone marrow were investigated 24 hours after intraperitoneal administration. The frequency of polychromatic erythrocytes with micronuclei was decreased from 7,4 +/- 0,18 by 1000 due to the action of chrysotile, from 2,8 +/- 0,42 for 1000 after the introduction of a modified sample. It is hypothesized that the ferric chloride modifies the surface of asbestos fibers that reduces the induction of free radicals which are the primary cause of and carcinogenic effects of chrysotile.}, } @article {pmid24336325, year = {2015}, author = {Tanaka, I and Osada, H and Fujii, M and Fukatsu, A and Hida, T and Horio, Y and Kondo, Y and Sato, A and Hasegawa, Y and Tsujimura, T and Sekido, Y}, title = {LIM-domain protein AJUBA suppresses malignant mesothelioma cell proliferation via Hippo signaling cascade.}, journal = {Oncogene}, volume = {34}, number = {1}, pages = {73-83}, pmid = {24336325}, issn = {1476-5594}, mesh = {Adaptor Proteins, Signal Transducing/metabolism ; Cell Adhesion ; Cell Line, Tumor ; Cell Proliferation ; Cytoplasm/metabolism ; *Gene Expression Regulation, Neoplastic ; Hippo Signaling Pathway ; Humans ; Immunohistochemistry ; LIM Domain Proteins/*metabolism ; Lentivirus/genetics ; Lung Neoplasms/*metabolism ; Mesothelioma/*metabolism ; Mesothelioma, Malignant ; Neurofibromin 2/metabolism ; Phenotype ; Phosphoproteins/metabolism ; Phosphorylation ; Protein Serine-Threonine Kinases/*metabolism ; RNA, Small Interfering/metabolism ; Signal Transduction ; Transcription Factors ; YAP-Signaling Proteins ; }, abstract = {Malignant mesothelioma (MM) is one of the most aggressive neoplasms usually associated with asbestos exposure and is highly refractory to current therapeutic modalities. MMs show frequent activation of a transcriptional coactivator Yes-associated protein (YAP), which is attributed to the neurofibromatosis type 2 (NF2)-Hippo pathway dysfunction, leading to deregulated cell proliferation and acquisition of a malignant phenotype. However, the whole mechanism of disordered YAP activation in MMs has not yet been well clarified. In the present study, we investigated various components of the NF2-Hippo pathway, and eventually found that MM cells frequently showed downregulation of LIM-domain protein AJUBA, a binding partner of large tumor suppressor type 2 (LATS2), which is one of the last-step kinases of the NF2-Hippo pathway. Although loss of AJUBA expression was independent of the alteration status of other Hippo pathway components, MM cell lines with AJUBA inactivation showed a more dephosphorylated (activated) level of YAP. Immunohistochemical analysis showed frequent downregulation of AJUBA in primary MMs, which was associated with YAP constitutive activation. We found that AJUBA transduction into MM cells significantly suppressed promoter activities of YAP-target genes, and the suppression of YAP activity by AJUBA was remarkably canceled by knockdown of LATS2. In connection with these results, transduction of AJUBA-expressing lentivirus significantly inhibited the proliferation and anchorage-independent growth of the MM cells that harbored ordinary LATS family expression. Taken together, our findings indicate that AJUBA negatively regulates YAP activity through the LATS family, and inactivation of AJUBA is a novel key mechanism in MM cell proliferation.}, } @article {pmid24327015, year = {2014}, author = {Linton, A and Cheng, YY and Griggs, K and Schedlich, L and Kirschner, MB and Gattani, S and Srikaran, S and Chuan-Hao Kao, S and McCaughan, BC and Klebe, S and van Zandwijk, N and Reid, G}, title = {An RNAi-based screen reveals PLK1, CDK1 and NDC80 as potential therapeutic targets in malignant pleural mesothelioma.}, journal = {British journal of cancer}, volume = {110}, number = {2}, pages = {510-519}, pmid = {24327015}, issn = {1532-1827}, mesh = {Apoptosis/drug effects/genetics ; Blood Proteins/genetics ; CDC2 Protein Kinase/genetics/*metabolism ; Cell Cycle/drug effects/genetics ; Cell Cycle Checkpoints/drug effects/genetics ; Cell Cycle Proteins/genetics/*metabolism ; Cell Line, Tumor ; Cisplatin/pharmacology ; Cytoskeletal Proteins ; DNA Repair/drug effects/genetics ; DNA Replication/drug effects/genetics ; Humans ; Lung Neoplasms/*drug therapy/genetics/*metabolism ; Mesothelioma/*drug therapy/genetics/*metabolism ; Mesothelioma, Malignant ; Molecular Targeted Therapy ; Nuclear Proteins/genetics/*metabolism ; Pleural Neoplasms/drug therapy/genetics/metabolism ; Prognosis ; Protein Serine-Threonine Kinases/genetics/*metabolism ; Proto-Oncogene Proteins/genetics/*metabolism ; Purines/pharmacology ; *RNA Interference ; Retrospective Studies ; Roscovitine ; Polo-Like Kinase 1 ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive tumour originating in the thoracic mesothelium. Prognosis remains poor with 9- to 12-month median survival, and new targets for treatments are desperately needed.

METHODS: Utilising an RNA interference (RNAi)-based screen of 40 genes overexpressed in tumours, including genes involved in the control of cell cycle, DNA replication and repair, we investigated potential therapeutic targets for MPM. Following in vitro characterisation of the effects of target silencing on MPM cells, candidates were assessed in tumour samples from 154 patients.

RESULTS: Gene knockdown in MPM cell lines identified growth inhibition following knockdown of NDC80, CDK1 and PLK1. Target knockdown induced cell-cycle arrest and increased apoptosis. Using small-molecule inhibitors specific for these three proteins also led to growth inhibition of MPM cell lines, and Roscovitine (inhibitor of CDK1) sensitised cells to cisplatin. Protein expression was also measured in tumour samples, with markedly variable levels of CDK1 and PLK1 noted. PLK1 expression in over 10% of cells correlated significantly with a poor prognosis.

CONCLUSION: These results suggest that RNAi-based screening has utility in identifying new targets for MPM, and that inhibition of NDC80, CDK1 and PLK1 may hold promise for treatment of this disease.}, } @article {pmid24324091, year = {2013}, author = {Corradi, M and Goldoni, M and Alinovi, R and Tiseo, M and Ampollini, L and Bonini, S and Carbognani, P and Casalini, A and Mutti, A}, title = {YKL-40 and mesothelin in the blood of patients with malignant mesothelioma, lung cancer and asbestosis.}, journal = {Anticancer research}, volume = {33}, number = {12}, pages = {5517-5524}, pmid = {24324091}, issn = {1791-7530}, mesh = {Adipokines/*blood ; Aged ; Asbestosis/*blood ; Biomarkers, Tumor/blood ; Case-Control Studies ; Chitinase-3-Like Protein 1 ; Cross-Sectional Studies ; Endothelin-1/blood ; Female ; GPI-Linked Proteins/*blood ; Humans ; Interleukin-8/blood ; Lectins/*blood ; Lung Neoplasms/*blood ; Male ; Mesothelin ; Mesothelioma/*blood ; Middle Aged ; Vascular Endothelial Growth Factor A/blood ; }, abstract = {BACKGROUND/AIM: In the diagnosis of malignant mesothelioma (MM) there still is a lack of specific and sensitive screening biomarkers: this study examined the discriminatory power of a panel of serum/plasma biomarkers.

PATIENTS AND METHODS: The study involved four groups: (a) individuals previously exposed to asbestos with asbestosis; (b) patients with MM; (c) patients with non-small cell lung cancer; and (d) controls without any evidence of malignancy. The concentrations of mesothelin, chitinase-3-like-1 (YKL-40), vascular endothelial growth factor (VEGF), endothelin-1, interleukin-8 (IL-8) and fibulin-3 in the serum of patients were determined.

RESULTS: Patients with MM had significantly higher serum levels of mesothelin (p<0.001), YKL-40 (p<0.001), IL-8 (p<0.001) and VEGF (p<0.01) than controls. The cut-off point for MM was 1.26 nM for mesothelin alone, and 167 pg/ml for YKL-40 alone; the presence of both markers above these cut-off levels improved diagnostic specificity.

CONCLUSION: The addition of YKL-40 may improve the specificity of mesothelin measurements alone for detecting patients with MM.}, } @article {pmid24303696, year = {2013}, author = {Filon, FL and Negro, C and De Michieli, P and Bovenzi, M}, title = {[Asbestos related cancers in seamen].}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {35}, number = {4}, pages = {206-210}, pmid = {24303696}, issn = {1592-7830}, mesh = {Asbestos/*adverse effects ; Humans ; Incidence ; Mesothelioma/epidemiology/*etiology ; *Naval Medicine ; Occupational Diseases/epidemiology/*etiology ; }, abstract = {Seamen and marine engineers were formerly exposed to asbestos used in gasket, pipes, valves and machinery. Ship motion and vibration can release asbestos in the surrounding space. Asbestos fibres may also be inhaled by workers involved in maintenance operations of vessels built before 1992 in Italy. History of asbestos exposure has been reported by workers and confirmed by a higher prevalence of pleural abnormalities and a significant excess of mesothelioma with a Standardized Incidence Ratio (SIR) ranging between 1.83 and 4.8 as a function of years of exposure. SIR for lung cancer ranged between 1.10 and 1.62. Mesothelioma in seamen and marine engineers represents about 2.5% of the overall Italian mesothelioma cases with a very long latency period (47.6 +/- 9.6 years). There is no epidemiological evidence for an excess risk of mesothelioma in fishermen.}, } @article {pmid24297134, year = {2013}, author = {Wright, CM and Kirschner, MB and van Zandwijk, N and Reid, G}, title = {Does miR-1 play a role in malignant pleural mesothelioma development and progression?.}, journal = {Chest}, volume = {144}, number = {6}, pages = {1971}, doi = {10.1378/chest.13-1657}, pmid = {24297134}, issn = {1931-3543}, mesh = {Apoptosis/*genetics ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/*genetics ; Male ; Mesothelioma/*genetics ; MicroRNAs/*genetics ; RNA, Neoplasm/*genetics ; }, } @article {pmid24257681, year = {2014}, author = {Toyokuni, S}, title = {Iron overload as a major targetable pathogenesis of asbestos-induced mesothelial carcinogenesis.}, journal = {Redox report : communications in free radical research}, volume = {19}, number = {1}, pages = {1-7}, pmid = {24257681}, issn = {1743-2928}, mesh = {Adsorption ; Animals ; Asbestos/*adverse effects ; Asbestosis/complications/epidemiology ; Benzoates/therapeutic use ; Carcinogens, Environmental/pharmacokinetics ; Carcinoma, Renal Cell/chemically induced/genetics ; *Cell Transformation, Neoplastic ; Comparative Genomic Hybridization ; Deferasirox ; Ferric Compounds/toxicity ; Ferric Oxide, Saccharated ; Genes, p16 ; Glucaric Acid/toxicity ; Humans ; Iron Chelating Agents/therapeutic use ; Iron Overload/drug therapy/*etiology/therapy ; Japan/epidemiology ; Kidney Neoplasms/chemically induced/genetics ; Male ; Mesothelioma/epidemiology/*etiology/genetics/prevention & control ; Mineral Fibers/adverse effects ; Peritoneal Neoplasms/chemically induced ; Phlebotomy ; Pleural Neoplasms/epidemiology/*etiology/genetics/prevention & control ; Rats ; Triazoles/therapeutic use ; }, abstract = {Few people expected that asbestos, a fibrous mineral, would be carcinogenic to humans. In fact, asbestos is a definite carcinogen in humans, causing a rare but aggressive cancer called malignant mesothelioma (MM). Mesothelial cells line the three somatic cavities and thus do not face the outer surface, but reduce the friction among numerous moving organs. MM has several characteristics: extremely long incubation period of 30-40 years after asbestos exposure, difficulty in clinical diagnosis at an early stage, and poor prognosis even under the current multimodal therapies. In Japan, 'Kubota shock' attracted considerable social attention in 2005 for asbestos-induced mesothelioma and, thereafter, the government enacted a law to provide the people suffering from MM a financial allowance. Several lines of recent evidence suggest that the major pathology associated with asbestos-induced MM is local iron overload, associated with asbestos exposure. Preclinical studies to prevent MM after asbestos exposure with iron reduction are in progress. In addition, novel target genes in mesothelial carcinogenesis have been discovered with recently recognized mesothelioma-prone families. Development of an effective preventive strategy is eagerly anticipated because of the long incubation period for MM.}, } @article {pmid24248693, year = {2013}, author = {Chirieac, LR and Barletta, JA and Yeap, BY and Richards, WG and Tilleman, T and Bueno, R and Baldini, EH and Godleski, J and Sugarbaker, DJ}, title = {Clinicopathologic characteristics of malignant mesotheliomas arising in patients with a history of radiation for Hodgkin and non-Hodgkin lymphoma.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {31}, number = {36}, pages = {4544-4549}, doi = {10.1200/JCO.2013.49.9616}, pmid = {24248693}, issn = {1527-7755}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Analysis of Variance ; Asbestos/*toxicity ; Carcinogens/*toxicity ; Female ; Hodgkin Disease/*radiotherapy ; Humans ; Kaplan-Meier Estimate ; Lung Neoplasms/chemically induced/*diagnosis/*etiology/mortality/pathology ; Lymphoma, Non-Hodgkin/*radiotherapy ; Male ; Mesothelioma/chemically induced/*diagnosis/*etiology/mortality/pathology ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/chemically induced/*diagnosis/*etiology/mortality/pathology ; Predictive Value of Tests ; Radiotherapy/adverse effects ; Risk Factors ; }, abstract = {PURPOSE: Studies have reported an association between pleural diffuse malignant mesothelioma (PDMM) and chest radiation for lymphoma. The clinicopathologic characteristics of malignant mesotheliomas arising in these patients have not been established.

PATIENTS AND METHODS: We studied 1,618 consecutive patients diagnosed with pleural PDMM from July 1993 to February 2008 and identified patients with a history of radiation for Hodgkin and non-Hodgkin lymphoma. We evaluated the histology in the surgical resection specimens and compared clinicopathologic features with overall survival.

RESULTS: We identified 22 patients who developed PDMM after chest radiation as part of their treatment for lymphoma (mean latency time, 21.4 years; 95% CI, 17.0 to 25.8 years). Asbestos bodies in lymphoma-associated PDMM were lower than in asbestos-associated PDMM (median count, 15 v 325 bodies, respectively; P < .001) and similar to an unexposed control group (median count, 15 v 10 bodies, respectively; P = .6). Seventeen lymphoma-associated PDMMs (77%) were epithelioid and five (23%) were biphasic. Seven PDMMs (32%) had unusual histologies (pleomorphic, myxoid, clear cell, and signet ring cell). Patients with lymphoma-associated PDMM were younger than patients with asbestos-associated PDMM (median age, 45 v 64 years, respectively; P < .001) and had a significantly longer overall survival time (median, 32.5 v 12.7 months, respectively; P = .018). In multivariate analysis, independent favorable predictors for overall survival were history of prior radiation (P = .022), female sex (P < .001), age ≤ 65 years (P = .005), cytoreductive surgery (P < .001), and epithelioid histology (P < .001).

CONCLUSION: Patients with lymphoma-associated PDMM are likely to have unusual histologic features, are significantly younger, and seem to have a longer overall survival compared with patients with asbestos-associated PDMM.}, } @article {pmid24239893, year = {2014}, author = {Lee, YJ and Park, IS and Lee, YJ and Shim, JH and Cho, MK and Nam, HS and Park, JW and Oh, MH and Lee, SH}, title = {Resveratrol contributes to chemosensitivity of malignant mesothelioma cells with activation of p53.}, journal = {Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association}, volume = {63}, number = {}, pages = {153-160}, doi = {10.1016/j.fct.2013.11.004}, pmid = {24239893}, issn = {1873-6351}, mesh = {Adenine Nucleotides/pharmacology ; Anticarcinogenic Agents/*pharmacology ; Antineoplastic Agents/*pharmacology ; Arabinonucleosides/pharmacology ; Base Sequence ; Cell Line, Tumor ; Clofarabine ; DNA Primers ; G1 Phase ; *Genes, p53 ; Humans ; Mesothelioma/drug therapy/*pathology ; Oncogene Proteins/genetics ; Polymerase Chain Reaction ; Resveratrol ; Stilbenes/*pharmacology ; }, abstract = {Resveratrol is a naturally occurring polyphenolic phytoalexin with chemopreventive properties. We previously reported a synergistic anti-proliferative effect of resveratrol and clofarabine against malignant mesothelioma (MM) cells. Here, we further investigated molecular mechanisms involved in the synergistic interaction of these compounds in MM MSTO-211H cells. Resveratrol, in combination with clofarabine, time-dependently induced a strong cytotoxic effect with the nuclear accumulation of phospho-p53 (p-p53) in MSTO-211H cells, but not in normal mesothelial MeT-5A cells. Combination treatment up-regulated the levels of p-p53, cleaved caspase-3, and cleaved PARP proteins. Gene silencing with p53-targeting siRNA attenuated the sensitivity of cells to the combined treatment of two compounds. Analyses of p53 DNA binding assay, p53 reporter gene assay, and RTP-CR toward p53-regulated genes, including Bax, PUMA, Noxa and p21, demonstrated that induced p-p53 is transcriptionally active. These results were further confirmed by the siRNA-mediated knockdown of p53 gene. Combination treatment significantly caused the accumulation of cells at G1 phase with the increases in the sub-G0/G1 peak, DNA ladder, nuclear fragmentation, and caspase-3/7 activity. Taken together, these results demonstrate that resveratrol and clofarabine synergistically elicit apoptotic signal via a p53-dependent pathway, and provide a scientific rationale for clinical evaluation of resveratrol as a promising chemopotentiator in MM.}, } @article {pmid24231697, year = {2013}, author = {Nakano, T and Otsuki, T}, title = {[Environmental air pollutants and the risk of cancer].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {40}, number = {11}, pages = {1441-1445}, pmid = {24231697}, issn = {0385-0684}, mesh = {Air Pollutants/*adverse effects ; Asbestos/adverse effects ; Environmental Exposure/adverse effects ; Humans ; Nanotubes/adverse effects ; Neoplasms/*chemically induced ; Risk Factors ; }, abstract = {The increased combustion of fossil fuels is one of the main reasons for the hazardous changes in the atmospheric composition. The sources of air pollution in urban areas include diesel motor vehicles, residential wood burning, and certain industrial processes. The types of air pollution include gases(eg, carbon monoxide, sulfur dioxide, nitrogen oxides, ozone)and suspended particulate matter(PM)such as PM2.5 and PM10 in diesel exhaust particles. PM2.5 refers to particles less than 2.5 micrometers in diameter. Long-term exposure to PM2.5 can increase the cardiovascular disease risk and lung cancer mortality. Although the role of PM2.5 in the etiology of lung cancer is not very clear, some researchers have shown evidence of increases in lung cancer mortality associated with exposure to PM2.5. Asbestos is also an important cause of cancer of the respiratory tract, particularly lung cancer and mesothelioma. The oncogenic hazards of asbestos fiber have been noted in cases of lowdose environmental exposure, as well in cases of high-dose occupational exposure. The use of asbestos has been strictly prohibited in Japan since 2006. However, large-scale natural disasters such as earthquakes, tsunamis, and typhoons can destroy many buildings and houses that were constructed before the ban on asbestos was initiated, thus resulting in the exposure of human beings to asbestos fibers. In the Cappadocian villages of Tuzkoy, Karain, and Sarihidir in Turkey, 50% of all deaths among villagers are caused by mesothelioma. This condition has been attributed to exposure to erionite, which is a type of fibrous zeolite mineral commonly found in this area of Turkey. However, pedigree studies of these villages showed that mesothelioma was prevalent in certain families but not in others, and that erionite exposure typically causes mesothelioma in those with a genetic predisposition to this disease. Recently, the germline BAP1 mutation was demonstrated in 2 different familial clusters of mesothelioma in the US.}, } @article {pmid24222877, year = {2013}, author = {Saba, R and Aronu, GN and Bhatti, RP and Mirrakhimov, AE and Anusim, N and Barbaryan, A and Kwatra, SG and Iroegbu, N}, title = {Malignant mesothelioma after household exposure to asbestos.}, journal = {Case reports in oncological medicine}, volume = {2013}, number = {}, pages = {570487}, pmid = {24222877}, issn = {2090-6706}, abstract = {Malignant mesothelioma (MM) is an aggressive cancer that has been closely linked to asbestos exposure. Initially recognized as an occupational cancer in male workers, MM was later found to occur in their family members as well. We report the case of an 89-year-old female who presented with abdominal distention, pain, and findings consistent with malignant ascites. Family history was significant for fatal mesothelioma in her husband of 40 years, who was a worker at a tile factory. The diagnosis of MM was confirmed on pathologic examination of the omental core biopsy.}, } @article {pmid24210155, year = {2013}, author = {Fleury Feith, J and Jaurand, MC}, title = {[Pleural lymphatics and pleural diseases related to fibres].}, journal = {Revue de pneumologie clinique}, volume = {69}, number = {6}, pages = {358-362}, doi = {10.1016/j.pneumo.2013.09.007}, pmid = {24210155}, issn = {1776-2561}, mesh = {Asbestos/adverse effects ; Humans ; Lymphatic Diseases/*chemically induced/epidemiology ; Lymphatic Vessels/pathology ; Mineral Fibers/*adverse effects ; Pleura/immunology/pathology ; Pleural Diseases/*chemically induced/epidemiology ; }, abstract = {It is now well established that some pleural diseases, pleural plaques and malignant mesothelioma are related to asbestos fibre exposure although the mechanism of action of asbestos fibres is not fully understood. The development of artificial mineral fibres and carbon nanotubes, which share some morphological characteristics similar to asbestos fibres, is a present concern in the context of pleural diseases. Pleural plaques develop only in the parietal pleura, and in the 1990s, clinical observations have shown that the early development of mesothelioma also occurred on the parietal pleura. The peculiarity of the parietal pleura in contrast to the visceral pleura is the presence of "stomas" which are communication holes between the pleural cavity and the parietal pleura lymphatics. Morphological observations by thoracoscopy and experimental studies have shown that inhaled fibres translocate to the pleural space and, in human, are present in the parietal pleura at specific anthracotic areas (blackspots). Fibres accumulate on the stomas, up to block and locally induce an inflammatory reaction with cytokines release, that can be the bed of mesothelioma. However, despite the experimental data and observations in human pathology, the mechanisms of fibre translocation into the pleura is not yet clearly established.}, } @article {pmid24200157, year = {2013}, author = {Nagai, H and Okazaki, Y and Chew, SH and Misawa, N and Miyata, Y and Shinohara, H and Toyokuni, S}, title = {Intraperitoneal administration of tangled multiwalled carbon nanotubes of 15 nm in diameter does not induce mesothelial carcinogenesis in rats.}, journal = {Pathology international}, volume = {63}, number = {9}, pages = {457-462}, doi = {10.1111/pin.12093}, pmid = {24200157}, issn = {1440-1827}, mesh = {Animals ; Asbestos/adverse effects ; *Cell Transformation, Neoplastic/chemistry ; Disease Models, Animal ; Environmental Health ; Female ; Injections, Intraperitoneal ; Male ; Mesothelioma/chemically induced/*pathology ; *Nanotubes, Carbon/adverse effects ; Rats ; Rats, Inbred F344 ; }, abstract = {Multiwalled carbon nanotubes (MWCNTs) have attracted public attention not only for their potential applications in engineering and materials science but also for possible environmental risks. MWCNTs share similar properties with asbestos, a definite human carcinogen causing malignant mesothelioma (MM), in that they are both biopersistent thin fibers with a high aspect ratio. Certain types of MWCNTs do induce MM in animal experiments. Though there are many different types of MWCNTs awaiting use in industry, there is little evidence about what types of MWCNTs present a high risk for MM in vivo. We have previously shown that the diameter of MWCNTs is one of the critical factors for mesothelial injury, which eventually leads to MM. Because of the extensive commercial use of MWCNTs, the properties of MWCNTs that determine carcinogenic activity should be clarified. Here we report that a high dose (10 mg) of a tangled form of pristine MWCNT (with a diameter of 15 nm) did not induce MM after intraperitoneal administration in rats, which were followed for up to 3 years after injection. This observation strengthens our previous finding that the rigidity, diameter, length and surface properties of MWCNTs are important factors in MM induction in vivo.}, } @article {pmid24195451, year = {2013}, author = {López-Abente, G and García-Gómez, M and Menéndez-Navarro, A and Fernández-Navarro, P and Ramis, R and García-Pérez, J and Cervantes, M and Ferreras, E and Jiménez-Muñoz, M and Pastor-Barriuso, R}, title = {Pleural cancer mortality in Spain: time-trends and updating of predictions up to 2020.}, journal = {BMC cancer}, volume = {13}, number = {}, pages = {528}, pmid = {24195451}, issn = {1471-2407}, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Child ; Child, Preschool ; Environmental Exposure/adverse effects ; Female ; History, 20th Century ; History, 21st Century ; Humans ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Pleural Neoplasms/epidemiology/etiology/history/*mortality ; Sex Factors ; Spain/epidemiology ; Young Adult ; }, abstract = {BACKGROUND: A total of 2,514,346 metric tons (Mt) of asbestos were imported into Spain from 1906 until the ban on asbestos in 2002. Our objective was to study pleural cancer mortality trends as an indicator of mesothelioma mortality and update mortality predictions for the periods 2011-2015 and 2016-2020 in Spain.

METHODS: Log-linear Poisson models were fitted to study the effect of age, period of death and birth cohort (APC) on mortality trends. Change points in cohort- and period-effect curvatures were assessed using segmented regression. Fractional power-link APC models were used to predict mortality until 2020. In addition, an alternative model based on national asbestos consumption figures was also used to perform long-term predictions.

RESULTS: Pleural cancer deaths increased across the study period, rising from 491 in 1976-1980 to 1,249 in 2006-2010. Predictions for the five-year period 2016-2020 indicated a total of 1,319 pleural cancer deaths (264 deaths/year). Forecasts up to 2020 indicated that this increase would continue, though the age-adjusted rates showed a levelling-off in male mortality from 2001 to 2005, corresponding to the lower risk in post-1960 generations. Among women, rates were lower and the mortality trend was also different, indicating that occupational exposure was possibly the single factor having most influence on pleural cancer mortality.

CONCLUSION: The cancer mortality-related consequences of human exposure to asbestos are set to persist and remain in evidence until the last surviving members of the exposed cohorts have disappeared. It can thus be assumed that occupationally-related deaths due to pleural mesothelioma will continue to occur in Spain until at least 2040.}, } @article {pmid24189076, year = {2014}, author = {Goodman, JE and Peterson, MK and Bailey, LA and Kerper, LE and Dodge, DG}, title = {Electricians' chrysotile asbestos exposure from electrical products and risks of mesothelioma and lung cancer.}, journal = {Regulatory toxicology and pharmacology : RTP}, volume = {68}, number = {1}, pages = {8-15}, doi = {10.1016/j.yrtph.2013.10.008}, pmid = {24189076}, issn = {1096-0295}, mesh = {Asbestos, Amphibole/analysis/*toxicity ; Asbestos, Serpentine/analysis/*toxicity ; Electrical Equipment and Supplies ; Europe ; Humans ; Inhalation Exposure/*adverse effects/analysis ; Lung Neoplasms/*chemically induced/epidemiology ; Mesothelioma/*chemically induced/epidemiology ; Occupational Exposure/*adverse effects/analysis ; Risk Assessment ; United States ; }, abstract = {Both mechanistic and epidemiology studies indicate chrysotile asbestos has a threshold below which it does not cause mesothelioma or lung cancer. We conducted a critical review to determine whether electricians are at increased risk for these cancers and, if so, whether their exposure to chrysotile in electrical products could be responsible. We found that most, but not all, epidemiology studies indicate electricians are at increased risk for both cancers. Studies that evaluated electricians' exposure to asbestos during normal work tasks have generally reported low concentrations in air; an experimental study showed that grinding or drilling products containing encapsulated chrysotile resulted in exposures to chrysotile fibers far below the OSHA permissible exposure limit and the cancer no observed adverse effect level. Studies of other craftsmen who often work in the vicinity of electricians, such as insulators, reported asbestos (including amphibole) exposures that were relatively high. Overall, the evidence does not indicate that exposure to chrysotile in electrical products causes mesothelioma or lung cancer in electricians. Rather, the most likely cause of lung cancer in electricians is smoking, and the most likely cause of mesothelioma is exposure to amphibole asbestos as a result of renovation/demolition work or working in the proximity of other skilled craftsmen.}, } @article {pmid24185840, year = {2013}, author = {Goswami, E and Craven, V and Dahlstrom, DL and Alexander, D and Mowat, F}, title = {Domestic asbestos exposure: a review of epidemiologic and exposure data.}, journal = {International journal of environmental research and public health}, volume = {10}, number = {11}, pages = {5629-5670}, pmid = {24185840}, issn = {1660-4601}, mesh = {Asbestos/*toxicity ; *Environmental Exposure ; Humans ; Lung Neoplasms/*chemically induced/epidemiology ; Mesothelioma/*chemically induced/epidemiology ; Risk Assessment ; }, abstract = {Inhalation of asbestos resulting from living with and handling the clothing of workers directly exposed to asbestos has been established as a possible contributor to disease. This review evaluates epidemiologic studies of asbestos-related disease or conditions (mesothelioma, lung cancer, and pleural and interstitial abnormalities) among domestically exposed individuals and exposure studies that provide either direct exposure measurements or surrogate measures of asbestos exposure. A meta-analysis of studies providing relative risk estimates (n = 12) of mesothelioma was performed, resulting in a summary relative risk estimate (SRRE) of 5.02 (95% confidence interval [CI]: 2.48-10.13). This SRRE pertains to persons domestically exposed via workers involved in occupations with a traditionally high risk of disease from exposure to asbestos (i.e., asbestos product manufacturing workers, insulators, shipyard workers, and asbestos miners). The epidemiologic studies also show an elevated risk of interstitial, but more likely pleural, abnormalities (n = 6), though only half accounted for confounding exposures. The studies are limited with regard to lung cancer (n = 2). Several exposure-related studies describe results from airborne samples collected within the home (n = 3), during laundering of contaminated clothing (n = 1) or in controlled exposure simulations (n = 5) of domestic exposures, the latter of which were generally associated with low-level chrysotile-exposed workers. Lung burden studies (n = 6) were also evaluated as a surrogate of exposure. In general, available results for domestic exposures are lower than the workers' exposures. Recent simulations of low-level chrysotile-exposed workers indicate asbestos levels commensurate with background concentrations in those exposed domestically.}, } @article {pmid24183360, year = {2013}, author = {Shih, CA and Ho, SP and Tsay, FW and Lai, KH and Hsu, PI}, title = {Diffuse malignant peritoneal mesothelioma.}, journal = {The Kaohsiung journal of medical sciences}, volume = {29}, number = {11}, pages = {642-645}, doi = {10.1016/j.kjms.2013.05.003}, pmid = {24183360}, issn = {2410-8650}, mesh = {Biopsy ; Humans ; Lung Neoplasms/*diagnosis/diagnostic imaging/pathology ; Male ; Mesothelioma/*diagnosis/diagnostic imaging/pathology ; Mesothelioma, Malignant ; Middle Aged ; Peritoneal Neoplasms/*diagnosis/diagnostic imaging/pathology ; Tomography, X-Ray Computed ; }, abstract = {Mesothelioma often originates in the pleura and less frequently in the peritoneum. This article describes a rare case of diffuse malignant peritoneal mesothelioma in a 54-year-old male construction worker who was admitted to our hospital with a 2-month history of progressive abdominal distention. Abdominal computed tomography revealed extensive peritoneal nodularity and omental cake along with massive ascites. Imaging findings initially suggested peritoneal carcinomatosis, primary peritoneal carcinoma, and tuberculous peritonitis. Laparoscopic biopsy of the omentum and peritoneum confirmed the diagnosis of malignant peritoneal mesothelioma of epitheloid type. Although systemic chemotherapy was administered, no tumor regression was found. The patient finally died of nosocomial infection.}, } @article {pmid24180083, year = {2013}, author = {Mastrangelo, G and Marangi, G and Ballarin, MN and Bellini, E and De Marzo, N and Eder, M and Finchi, A and Gioffrè, F and Marcolina, D and Tessadri, G and Zannol, F and Altafini, I and Belluso, E and Zaina, S and Agnesi, R and Scoizzato, L and Fedeli, U and Cegolon, L and Valentini, F and Marchiori, L}, title = {Post-occupational health surveillance of asbestos workers.}, journal = {La Medicina del lavoro}, volume = {104}, number = {5}, pages = {351-358}, pmid = {24180083}, issn = {0025-7818}, mesh = {Asbestos/*adverse effects/analysis ; Asbestosis/blood/*epidemiology/etiology ; Biomarkers ; Early Detection of Cancer/economics/methods ; Follow-Up Studies ; Health Policy ; Humans ; Italy ; Liability, Legal ; Lung Neoplasms/diagnosis/economics/epidemiology/etiology/prevention & control ; Male ; Mesothelioma/diagnosis/economics/epidemiology/etiology/prevention & control ; Middle Aged ; Mineral Fibers/analysis ; *Occupational Exposure ; Occupations ; Osteopontin/blood ; Pleural Neoplasms/diagnosis/economics/epidemiology/etiology/prevention & control ; *Population Surveillance/methods ; Program Evaluation ; Reproducibility of Results ; Respiratory Function Tests ; Retirement ; Retrospective Studies ; Smoking ; }, abstract = {BACKGROUND: Italian law requires an extensive health surveillance of workers after cessation of their employment status in the case of occupational exposure to carcinogens, including asbestos. Nonetheless, Italian law does not specify the timeframe of these clinical checks, nor who has financial and organizational responsibility for this surveillance. A literature search confirmed a lack of consensus around the objectives and methods to follow up workers with past occupational exposure to asbestos.

OBJECTIVES: To develop an updated evidence-based methodology for an appropriate health surveillance programme.

METHODS: We present an overview of the field experience developed by the Veneto Region from 2000 to 2011, and new studies that could contribute to establishing a national policy for the medical surveillance of workers with past asbestos exposure.

RESULTS: There were three specific topics: (1) definition of a reliable method to identify asbestos workers (through multiple sources and procedures that meet current confidentiality regulations); (2) detection of asbestos fibres in biological media (to support the etiological diagnosis of asbestos-related diseases); (3) creation of a national protocol of health surveillance (through the assessment of policies developed by other Regions in this field, and recruiting from these regions a cohort of past-exposed workers: the epidemiological study should offer relevant suggestions for specific surveillance approaches, based on either estimated cumulative asbestos exposure or detection of x-ray patterns of pleural plaques and/or asbestosis).

CONCLUSIONS: These studies will support the Regions in setting up health care policies directed at workers with past asbestos exposure.}, } @article {pmid24179653, year = {2013}, author = {Günday, M and Erinanç, H and Geredeli, C}, title = {Unusual region for pericardial malignant mesothelioma: cutaneous manifestation in a Turkish woman.}, journal = {Rare tumors}, volume = {5}, number = {3}, pages = {e41}, pmid = {24179653}, issn = {2036-3605}, abstract = {Malignant mesothelioma is a disease that originates from mesenchymal cells. It is related to the occupational or environmental exposure to asbestos. The treatment remains controversial because it is commonly diagnosed at a very late stage, and the prognosis is very poor. In this report, we present a 37-year-old female patient who was admitted with shortness of breath, palpitation and inability to sleep on her back for the previous 10 days. A large pericardial effusion was detected on echocardiography. Pericardiocentesis was performed and the patient's symptoms were alleviated. However, approximately 7 months later, she was readmitted to the clinic with complaints of a mass at the incision site. Pathological examination of the mass yielded a diagnosis of pericardial malignant mesothelioma. Malignant mesothelioma is a rare occurrence, and to our knowledge, there are no reports in the English literature of pericardial malignant mesothelioma local invasion to an incision site.}, } @article {pmid24170217, year = {2014}, author = {Bayram, M and Dongel, I and Akbaş, A and Benli, I and Akkoyunlu, ME and Bakan, ND}, title = {Serum biomarkers in patients with mesothelioma and pleural plaques and healthy subjects exposed to naturally occurring asbestos.}, journal = {Lung}, volume = {192}, number = {1}, pages = {197-203}, pmid = {24170217}, issn = {1432-1750}, mesh = {Aged ; Area Under Curve ; Asbestos/*adverse effects ; Biomarkers, Tumor/*blood ; Case-Control Studies ; Chi-Square Distribution ; Diagnosis, Differential ; GPI-Linked Proteins/*blood ; Humans ; Inhalation Exposure/adverse effects ; Linear Models ; Mesothelin ; Mesothelioma/*blood/diagnosis/etiology ; Middle Aged ; Osteopontin/*blood ; Pleura/*pathology ; Pleural Neoplasms/*blood/diagnosis/etiology ; Predictive Value of Tests ; ROC Curve ; Risk Factors ; Smoking/adverse effects ; Turkey ; }, abstract = {PURPOSE: This study investigated the diagnostic accuracy of the serum biomarkers osteopontin and mesothelin in discriminating mesothelioma patients from those with other, benign conditions and whether levels of the biomarkers differed in subjects who had inhaled naturally occurring asbestos compared with a non-exposed control group.

METHODS: This cross-sectional study studied 24 subjects with mesothelioma, 279 subjects with pleural plaques, 123 "healthy exposed," and 120 control subjects. The Kruskal-Wallis test was performed to compare mesothelin and osteopontin levels of the groups, and receiver operating characteristics curves were generated to determine diagnostic yields of both biomarkers. Multiple linear regression analyses were used to identify associated covariates with osteopontin and mesothelin levels.

RESULTS: Serum osteopontin and mesothelin levels were higher in mesothelioma than in benign asbestos-related diseases and healthy exposed subjects. Both biomarker levels were independently associated with mesothelioma, age and smoking pack years. Mesothelin levels were also associated with body mass index. The sensitivity and specificity of osteopontin in distinguishing mesothelioma from the three other groups were 75 and 86 %, respectively; those of mesothelin were 58 and 83 %, respectively. The sensitivity and specificity to discriminate mesothelioma from pleural plaques and healthy subjects were 93 and 73 %, respectively, if osteopontin and mesothelin levels were higher than their optimal cut off levels.

CONCLUSIONS: The combination of serum osteopontin and mesothelin levels can help to distinguish mesothelioma from benign asbestos-related diseases and asbestos-exposed subjects.}, } @article {pmid24168922, year = {2013}, author = {Muraoka, T and Soh, J and Toyooka, S and Aoe, K and Fujimoto, N and Hashida, S and Maki, Y and Tanaka, N and Shien, K and Furukawa, M and Yamamoto, H and Asano, H and Tsukuda, K and Kishimoto, T and Otsuki, T and Miyoshi, S}, title = {The degree of microRNA-34b/c methylation in serum-circulating DNA is associated with malignant pleural mesothelioma.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {82}, number = {3}, pages = {485-490}, doi = {10.1016/j.lungcan.2013.09.017}, pmid = {24168922}, issn = {1872-8332}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics/*metabolism ; DNA/*analysis/blood ; DNA Methylation ; Down-Regulation ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/*diagnosis/genetics ; Male ; Mesothelioma/*diagnosis/genetics ; Mesothelioma, Malignant ; MicroRNAs/genetics/*metabolism ; Middle Aged ; Neoplasm Staging ; Pleural Neoplasms/*diagnosis/genetics ; Real-Time Polymerase Chain Reaction ; }, abstract = {OBJECTIVES: Malignant pleural mesothelioma (MPM) is an aggressive tumor with a poor prognosis. microRNA-34b/c (miR-34b/c), which plays an important role in the pathogenesis of MPM, is frequently downregulated by DNA methylation in approximately 90% of MPM cases. In this study, we estimated the degree of miR-34b/c methylation in serum-circulating DNA using a digital methylation specific PCR assay (MSP).

MATERIALS AND METHODS: A real-time MSP assay was performed using the SYBR Green method. The melting temperature (Tm) of each PCR product was examined using a melting curve analysis. For a digital MSP assay, 40 wells were analyzed per sample. A total of 110 serum samples from 48 MPM cases, 21 benign asbestos pleurisy (BAP) cases, and 41 healthy volunteers (HVs) were examined.

RESULTS: Positive range of Tm value for miR-34b/c methylation was defined as 77.71-78.79 °C which was the mean ± 3 standard deviations of 40 wells of a positive control. The number of miR-34b/c methylated wells was counted per sample according to this criterion. The number of miR-34b/c methylated wells in MPM cases was significantly higher than that in BAP cases (P=0.03) or HVs (P<0.001). Advanced MPM cases tended to have higher number of miR-34b/c methylated wells than early MPM cases. Receiver-operating characteristic (ROC) curve analysis revealed that three number of miR-34b/c methylated wells per sample was the best cut-off of positivity of MPM with a 67% of sensitivity and a 77% specificity for prediction. The area under the ROC curve was 0.77.

CONCLUSIONS: Our digital MSP assay can quantify miR-34b/c methylation in serum-circulating DNA. The degree of miR-34b/c methylation in serum-circulating DNA is associated with MPM, suggesting that this approach might be useful for the establishment of a new detection system for MPM.}, } @article {pmid24167356, year = {2013}, author = {Creaney, J and Sneddon, S and Dick, IM and Dare, H and Boudville, N and Musk, AW and Skates, SJ and Robinson, BW}, title = {Comparison of the diagnostic accuracy of the MSLN gene products, mesothelin and megakaryocyte potentiating factor, as biomarkers for mesothelioma in pleural effusions and serum.}, journal = {Disease markers}, volume = {35}, number = {2}, pages = {119-127}, pmid = {24167356}, issn = {1875-8630}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*blood ; Case-Control Studies ; Female ; GPI-Linked Proteins/*blood ; Humans ; Limit of Detection ; Male ; Mesothelin ; Mesothelioma/*blood/diagnosis ; Middle Aged ; Pleural Effusion, Malignant/*blood/diagnosis ; ROC Curve ; Renal Insufficiency, Chronic/blood ; }, abstract = {The MSLN gene products, soluble mesothelin and megakaryocyte potentiating factor (MPF), are being investigated as biomarkers for the asbestos-related cancer malignant mesothelioma (MM). Pleural fluid biomarkers of MM can be elevated when serum levels remain normal. The aim of this study was to determine if this was true for MPF and to compare levels of mesothelin. Biomarker concentrations were compared in 66 MM patients, 39 patients with other malignancies, 37 with benign disease, 18 asbestos-exposed healthy individuals, and 53 patients with chronic kidney disease. In pleural effusions, MPF and soluble mesothelin concentrations were both significantly elevated in MM patients relative to controls. No significant difference between the area under the receiver operator curve (AUC) for MPF (0.945 ± 0.02) and mesothelin (0.928 ± 0.03) when distinguishing MM from all other causes of effusion was observed. MPF and mesothelin serum concentrations were highly correlated and of equivalent diagnostic accuracy with AUCs of 0.813 ± 0.04 and 0.829 ± 0.03, respectively. Serum levels of both markers increased with decreasing kidney function. In conclusion, MPF is elevated in the pleural effusions of MM patients similar to that of mesothelin. Mesothelin and MPF convey equivalent diagnostic information for distinguishing MM from other diseases in pleural effusions as well as serum.}, } @article {pmid24161718, year = {2013}, author = {Creaney, J and Dick, IM and Segal, A and Musk, AW and Robinson, BW}, title = {Pleural effusion hyaluronic acid as a prognostic marker in pleural malignant mesothelioma.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {82}, number = {3}, pages = {491-498}, doi = {10.1016/j.lungcan.2013.09.016}, pmid = {24161718}, issn = {1872-8332}, mesh = {Aged ; Biomarkers, Tumor/*metabolism ; Female ; GPI-Linked Proteins/metabolism ; Humans ; Hyaluronic Acid/*metabolism ; Lung Neoplasms/*diagnosis/mortality ; Male ; Mesothelin ; Mesothelioma/*diagnosis/mortality ; Mesothelioma, Malignant ; Middle Aged ; Pleural Cavity/metabolism ; Pleural Effusion/*diagnosis/mortality ; Pleural Neoplasms/*diagnosis/mortality ; Prognosis ; Survival Analysis ; }, abstract = {BACKGROUND: Malignant mesothelioma (MM), a primarily asbestos-induced tumour, has a poor prognosis, with over-all 5-year survival less than 5%. Tumour biomarkers are being intensely investigated in MM as aids to diagnosis and prognosis. Hyaluronic acid (HA) is produced in MM but its role in prognostication remains uncertain.

MATERIALS AND METHODS: HA concentrations were determined in matching serum and pleural effusion of 96 MM patients, 26 lung cancer patients and 42 patients with benign effusions resulting from infectious, cardiac, renal, liver and rheumatoid diseases and compared to the current 'best practice' biomarker, mesothelin. Liver and kidney function were determined for each patient. Diagnostic accuracy was determined by area under the receiver operator characteristic curve (AUC) analysis following logistic regression modelling. Difference in survival between groups was determined by both log-rank test and Cox proportional hazards regression modelling.

RESULTS: For effusion HA, the AUC (IQ range) was 0.89 (0.82-0.94) and for effusion mesothelin, it was 0.85 (0.78-0.90). Serum HA was not diagnostically useful. A combined measure of effusion HA, and serum and effusion mesothelin had an AUC of 0.92 (0.86-0.96), which was significantly higher than effusion mesothelin alone. Effusion HA had a biphasic distribution in MM patients, dichotomised at a concentration of 75 mg/L. The median survival of MM patients with high effusion HA was 18.0 (13.7-22.4) months, significantly longer than those with low HA effusion levels (12.6 months (8.4-16.8), p=0.004). Serum HA, and effusion and serum mesothelin were not significant prognostic indicators.

CONCLUSION: This study demonstrates that a combined biomarker panel has greater diagnostic accuracy than effusion mesothelin alone, and that significant prognostic information is provided by effusion HA.}, } @article {pmid24160326, year = {2013}, author = {Qi, F and Okimoto, G and Jube, S and Napolitano, A and Pass, HI and Laczko, R and Demay, RM and Khan, G and Tiirikainen, M and Rinaudo, C and Croce, A and Yang, H and Gaudino, G and Carbone, M}, title = {Continuous exposure to chrysotile asbestos can cause transformation of human mesothelial cells via HMGB1 and TNF-α signaling.}, journal = {The American journal of pathology}, volume = {183}, number = {5}, pages = {1654-1666}, pmid = {24160326}, issn = {1525-2191}, support = {NCI R01 CA106567/CA/NCI NIH HHS/United States ; R01 CA160715/CA/NCI NIH HHS/United States ; R01 CA106567/CA/NCI NIH HHS/United States ; P30 CA071789/CA/NCI NIH HHS/United States ; NCI R01 CA160715-0A/CA/NCI NIH HHS/United States ; P01 CA114047/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Asbestos, Crocidolite/toxicity ; Asbestos, Serpentine/*toxicity ; Cadherins/metabolism ; Cell Death/drug effects ; Cell Line ; Cell Shape/drug effects ; Cell Transformation, Neoplastic/*metabolism/*pathology ; Epithelium/drug effects/metabolism/*pathology ; Gene Expression Profiling ; Gene Expression Regulation/drug effects ; Genome, Human/genetics ; HMGB1 Protein/blood/*metabolism ; Humans ; Mice ; Signal Transduction/*drug effects/genetics ; Transcription, Genetic/drug effects ; Tumor Necrosis Factor-alpha/*metabolism ; beta Catenin/metabolism ; }, abstract = {Malignant mesothelioma is strongly associated with asbestos exposure. Among asbestos fibers, crocidolite is considered the most and chrysotile the least oncogenic. Chrysotile accounts for more than 90% of the asbestos used worldwide, but its capacity to induce malignant mesothelioma is still debated. We found that chrysotile and crocidolite exposures have similar effects on human mesothelial cells. Morphological and molecular alterations suggestive of epithelial-mesenchymal transition, such as E-cadherin down-regulation and β-catenin phosphorylation followed by nuclear translocation, were induced by both chrysotile and crocidolite. Gene expression profiling revealed high-mobility group box-1 protein (HMGB1) as a key regulator of the transcriptional alterations induced by both types of asbestos. Crocidolite and chrysotile induced differential expression of 438 out of 28,869 genes interrogated by oligonucleotide microarrays. Out of these 438 genes, 57 were associated with inflammatory and immune response and cancer, and 14 were HMGB1 targeted genes. Crocidolite-induced gene alterations were sustained, whereas chrysotile-induced gene alterations returned to background levels within 5 weeks. Similarly, HMGB1 release in vivo progressively increased for 10 or more weeks after crocidolite exposure, but returned to background levels within 8 weeks after chrysotile exposure. Continuous administration of chrysotile was required for sustained high serum levels of HMGB1. These data support the hypothesis that differences in biopersistence influence the biological activities of these two asbestos fibers.}, } @article {pmid24158772, year = {2014}, author = {Toyokawa, G and Takenoyama, M and Hirai, F and Toyozawa, R and Inamasu, E and Kojo, M and Morodomi, Y and Shiraishi, Y and Takenaka, T and Yamaguchi, M and Shimokawa, M and Seto, T and Ichinose, Y}, title = {Gemcitabine and vinorelbine as second-line or beyond treatment in patients with malignant pleural mesothelioma pretreated with platinum plus pemetrexed chemotherapy.}, journal = {International journal of clinical oncology}, volume = {19}, number = {4}, pages = {601-606}, pmid = {24158772}, issn = {1437-7772}, mesh = {Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage ; Asbestos/toxicity ; Cisplatin/administration & dosage ; Combined Modality Therapy ; Deoxycytidine/administration & dosage/*analogs & derivatives ; Disease-Free Survival ; Drug-Related Side Effects and Adverse Reactions/classification/pathology ; Female ; Glutamates/*administration & dosage ; Guanine/administration & dosage/*analogs & derivatives ; Humans ; Lung Neoplasms/chemically induced/*drug therapy/pathology ; Male ; Mesothelioma/chemically induced/*drug therapy/pathology ; Mesothelioma, Malignant ; Middle Aged ; Neoplasm Staging ; Pemetrexed ; Pleural Neoplasms/chemically induced/*drug therapy/pathology ; Vinblastine/administration & dosage/*analogs & derivatives ; Vinorelbine ; Gemcitabine ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive neoplasm that responds poorly to chemotherapy. Although treatment with pemetrexed in combination with cisplatin serves as first-line chemotherapy for MPM, the optimal second-line and beyond therapy has not yet been fully examined.

METHODS: Between March 2008 and October 2011, 17 consecutive Japanese patients pretreated with at least one regimen of platinum plus pemetrexed chemotherapy received gemcitabine and vinorelbine. Responses, survival time, and toxicity were retrospectively evaluated.

RESULTS: Response [partial response (PR) + complete response (CR)] and disease control [stable disease (SD) + PR + CR] rates were 18 and 82 %, respectively. The median progression-free survival (PFS) after combination chemotherapy was 6.0 months, whereas the median overall survival (OS) was 11.2 months. Grade 3 or 4 neutropenia and anemia were observed in 41 and 29 % of patients, respectively, and one patient experienced febrile neutropenia. Grade 3 or 4 nonhematologic toxicities included constipation (6 %) and phlebitis (6 %).

CONCLUSION: Combination chemotherapy using gemcitabine with vinorelbine was shown to have moderate activity in Japanese MPM patients pretreated with platinum plus pemetrexed chemotherapy. A further multicenter phase II trial is warranted to confirm the efficacy and safety of this combination treatment.}, } @article {pmid24148817, year = {2013}, author = {Reid, G and Pel, ME and Kirschner, MB and Cheng, YY and Mugridge, N and Weiss, J and Williams, M and Wright, C and Edelman, JJ and Vallely, MP and McCaughan, BC and Klebe, S and Brahmbhatt, H and MacDiarmid, JA and van Zandwijk, N}, title = {Restoring expression of miR-16: a novel approach to therapy for malignant pleural mesothelioma.}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {24}, number = {12}, pages = {3128-3135}, doi = {10.1093/annonc/mdt412}, pmid = {24148817}, issn = {1569-8041}, mesh = {Animals ; Cell Line, Tumor ; Deoxycytidine/analogs & derivatives/pharmacology ; Drug Resistance, Neoplasm ; Gene Expression Regulation, Neoplastic ; Glutamates/pharmacology ; Guanine/analogs & derivatives/pharmacology ; Humans ; Lung Neoplasms/*metabolism/pathology/therapy ; Mesothelioma/*metabolism/pathology/therapy ; Mesothelioma, Malignant ; Mice ; Mice, Nude ; MicroRNAs/*genetics/metabolism ; Neoplasm Transplantation ; Pemetrexed ; Pleural Neoplasms/*metabolism/pathology/therapy ; RNA Interference ; Transfection ; Tumor Burden ; Gemcitabine ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is recalcitrant to treatment and new approaches to therapy are needed. Reduced expression of miR-15/16 in a range of cancer types has suggested a tumour suppressor function for these microRNAs, and re-expression has been shown to inhibit tumour cell proliferation. The miR-15/16 status in MPM is largely unknown.

MATERIALS AND METHODS: MicroRNA expression was analysed by TaqMan-based RT-qPCR in MPM tumour specimens and cell lines. MicroRNA expression was restored in vitro using microRNA mimics, and effects on proliferation, drug sensitivity and target gene expression were assessed. Xenograft-bearing mice were treated with miR-16 mimic packaged in minicells targeted with epidermal growth factor receptor (EGFR)-specific antibodies.

RESULTS: Expression of the miR-15 family was consistently downregulated in MPM tumour specimens and cell lines. A decrease of 4- to 22-fold was found when tumour specimens were compared with normal pleura. When MPM cell lines were compared with the normal mesothelial cell line MeT-5A, the downregulation of miR-15/16 was 2- to 10-fold. Using synthetic mimics to restore miR-15/16 expression led to growth inhibition in MPM cell lines but not in MeT-5A cells. Growth inhibition caused by miR-16 correlated with downregulation of target genes including Bcl-2 and CCND1, and miR-16 re-expression sensitised MPM cells to pemetrexed and gemcitabine. In xenograft-bearing nude mice, intravenous administration of miR-16 mimics packaged in minicells led to consistent and dose-dependent inhibition of MPM tumour growth.

CONCLUSIONS: The miR-15/16 family is downregulated and has tumour suppressor function in MPM. Restoring miR-16 expression represents a novel therapeutic approach for MPM.}, } @article {pmid24142981, year = {2013}, author = {Langevin, SM and O'Sullivan, MH and Valerio, JL and Pawlita, M and Applebaum, KM and Eliot, M and McClean, MD and Kelsey, KT}, title = {Occupational asbestos exposure is associated with pharyngeal squamous cell carcinoma in men from the greater Boston area.}, journal = {Occupational and environmental medicine}, volume = {70}, number = {12}, pages = {858-863}, pmid = {24142981}, issn = {1470-7926}, support = {T32ES07272/ES/NIEHS NIH HHS/United States ; K01 OH009390/OH/NIOSH CDC HHS/United States ; R01CA078609/CA/NCI NIH HHS/United States ; R01CA100679/CA/NCI NIH HHS/United States ; R01CA121147/CA/NCI NIH HHS/United States ; T32 ES007272/ES/NIEHS NIH HHS/United States ; R01 CA078609/CA/NCI NIH HHS/United States ; R01 CA121147/CA/NCI NIH HHS/United States ; R01 CA100679/CA/NCI NIH HHS/United States ; K01OH009390/OH/NIOSH CDC HHS/United States ; }, mesh = {Asbestos/*toxicity ; Boston/epidemiology ; Carcinoma, Squamous Cell/epidemiology/*etiology ; Case-Control Studies ; Humans ; Incidence ; Male ; Middle Aged ; Occupational Diseases/epidemiology/*etiology ; Occupational Exposure/*adverse effects ; Pharyngeal Neoplasms/epidemiology/*etiology ; Risk Factors ; }, abstract = {OBJECTIVES: Asbestos is the name given to a group of naturally occurring silicate mineral fibres that were widely used in industry during the 20th century due to their desirable physical properties. Although use in the USA has fallen over the last three decades, significant exposure in the developing world continues and the burden of disease is considerable. Asbestos is a known risk factor for several malignant diseases, including lung cancer and mesothelioma, and has more recently been implicated in pharyngeal and laryngeal cancer. However, studies of asbestos and cancers of the larynx or pharynx with adequate sample size that control for major head and neck squamous cell carcinoma (HNSCC) risk factors remain relatively sparse.

METHODS: We report findings from a case-control study of 674 incident male HNSCC cases from the greater Boston region and 857 population-based male controls, matched on age (±3 years), sex, and town or neighbourhood of residence. Multivariable logistic regression was used to assess the association between occupational asbestos exposure and HNSCC by primary tumour site.

RESULTS: 190 cases (28.2%) and 203 controls (23.7%) reported occupational exposure to asbestos. Occupational asbestos exposure was associated with elevated risk of pharyngeal carcinoma in men (OR 1.41, 95% CI 1.01 to 1.97), adjusted for age, race, smoking, alcohol consumption, education, income and HPV16 serology, with borderline increasing risk for each decade in the exposed occupation (OR 1.10, 95% CI 0.99 to 1.23).

CONCLUSIONS: These observations are consistent with mounting evidence that asbestos is a risk factor for pharyngeal cancer.}, } @article {pmid24142974, year = {2014}, author = {Daniels, RD and Kubale, TL and Yiin, JH and Dahm, MM and Hales, TR and Baris, D and Zahm, SH and Beaumont, JJ and Waters, KM and Pinkerton, LE}, title = {Mortality and cancer incidence in a pooled cohort of US firefighters from San Francisco, Chicago and Philadelphia (1950-2009).}, journal = {Occupational and environmental medicine}, volume = {71}, number = {6}, pages = {388-397}, pmid = {24142974}, issn = {1470-7926}, support = {N02 PC015105/PC/NCI NIH HHS/United States ; CC999999//Intramural CDC HHS/United States ; /ImNIH/Intramural NIH HHS/United States ; N01PC35136/CA/NCI NIH HHS/United States ; N01PC35139/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Cause of Death ; Chicago/epidemiology ; Cohort Studies ; Digestive System Neoplasms/epidemiology/*etiology/mortality ; Female ; *Firefighters ; Humans ; Incidence ; Lung Neoplasms/epidemiology/*etiology/mortality ; Male ; Mesothelioma/epidemiology/*etiology/mortality ; Mesothelioma, Malignant ; Middle Aged ; Neoplasms/epidemiology/etiology ; Occupational Diseases/epidemiology/*etiology/mortality ; Occupational Exposure/*adverse effects ; Philadelphia/epidemiology ; Respiratory Tract Neoplasms/epidemiology/*etiology/mortality ; San Francisco/epidemiology ; }, abstract = {OBJECTIVES: To examine mortality patterns and cancer incidence in a pooled cohort of 29 993 US career firefighters employed since 1950 and followed through 2009.

METHODS: Mortality and cancer incidence were evaluated by life table methods with the US population referent. Standardised mortality (SMR) and incidence (SIR) ratios were determined for 92 causes of death and 41 cancer incidence groupings. Analyses focused on 15 outcomes of a priori interest. Sensitivity analyses were conducted to examine the potential for significant bias.

RESULTS: Person-years at risk totalled 858 938 and 403 152 for mortality and incidence analyses, respectively. All-cause mortality was at expectation (SMR=0.99, 95% CI 0.97 to 1.01, n=12 028). There was excess cancer mortality (SMR=1.14, 95% CI 1.10 to 1.18, n=3285) and incidence (SIR=1.09, 95% CI 1.06 to 1.12, n=4461) comprised mainly of digestive (SMR=1.26, 95% CI 1.18 to 1.34, n=928; SIR=1.17, 95% CI 1.10 to 1.25, n=930) and respiratory (SMR=1.10, 95% CI 1.04 to 1.17, n=1096; SIR=1.16, 95% CI 1.08 to 1.24, n=813) cancers. Consistent with previous reports, modest elevations were observed in several solid cancers; however, evidence of excess lymphatic or haematopoietic cancers was lacking. This study is the first to report excess malignant mesothelioma (SMR=2.00, 95% CI 1.03 to 3.49, n=12; SIR=2.29, 95% CI 1.60 to 3.19, n=35) among US firefighters. Results appeared robust under differing assumptions and analytic techniques.

CONCLUSIONS: Our results provide evidence of a relation between firefighting and cancer. The new finding of excess malignant mesothelioma is noteworthy, given that asbestos exposure is a known hazard of firefighting.}, } @article {pmid24141556, year = {2014}, author = {Suzuki, H and Asami, K and Hirashima, T and Okamoto, N and Yamadori, T and Tamiya, M and Morishita, N and Shiroyama, T and Takeoka, S and Osa, A and Azuma, Y and Okishio, K and Kawaguchi, T and Atagi, S and Kawase, I}, title = {Stratification of malignant pleural mesothelioma prognosis using recursive partitioning analysis.}, journal = {Lung}, volume = {192}, number = {1}, pages = {191-195}, pmid = {24141556}, issn = {1432-1750}, mesh = {Aged ; Algorithms ; Asbestos/adverse effects ; Biomarkers/blood ; Chest Pain/etiology ; *Decision Support Techniques ; Female ; Hemoglobins/analysis ; Humans ; Japan ; Kaplan-Meier Estimate ; L-Lactate Dehydrogenase/blood ; Leukocyte Count ; Lung Neoplasms/blood/*diagnosis/etiology/mortality/pathology ; Male ; Mesothelioma/blood/*diagnosis/etiology/mortality/pathology ; Mesothelioma, Malignant ; Multivariate Analysis ; Neoplasm Staging ; Platelet Count ; Pleural Neoplasms/blood/*diagnosis/etiology/mortality/pathology ; Predictive Value of Tests ; Proportional Hazards Models ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Smoking/adverse effects ; Time Factors ; }, abstract = {PURPOSE: Prognostic factors and complicated prognostic models have been proposed for malignant pleural mesothelioma (MPM). This study was designed to stratify MPM prognosis by using a simple model.

METHODS: Patients diagnosed with MPM in the past 10 years (n = 122) were examined retrospectively. Data on the presence of chest pain, performance status (PS), asbestos exposure, smoking status, white blood cell count (WBC), haemoglobin (Hb) concentration, platelet count (PLT), lactate dehydronate (LD), histology, stage, and date of death or censored status were collected. After the factors were examined in the univariate analysis, recursive partitioning analysis was performed.

RESULTS: Statistically significant factors related to survival were the type of histology, stage, PS, WBC, PLT, Hb concentration, and LD. Histology, stage, PS, and Hb concentration were used in multivariate analysis. Stage and Hb concentration showed good statistical significance, whereas PS was borderline significant. The survival analyses were stratified into five groups by PS, stage, Hb concentration, and chest pain using recursive partitioning analysis. Group A comprised patients showing the most favourable prognoses (PS 0-2 and Hb concentration >12.1 g dL(-1) or PS 0-2 and Hb concentration ≤12.1 g dL(-1) without pain), and group B comprised the remaining patients. The median overall survival in groups A and B was 563 days (95 % confidence interval [CI] 502-779) and 157 days (95 % CI 115-224), respectively (hazard ratio of 5.44 [3.46-8.53, P < 0.0001]).

CONCLUSIONS: The MPM patients with PS 0-2 and Hb concentration >12.1 or ≤12.1 g dL(-1) without chest pain had favourable prognoses.}, } @article {pmid24134457, year = {2014}, author = {Dodson, RF and Mark, EJ and Poye, LW}, title = {Biodurability/retention of Libby amphiboles in a case of mesothelioma.}, journal = {Ultrastructural pathology}, volume = {38}, number = {1}, pages = {45-51}, doi = {10.3109/01913123.2013.821194}, pmid = {24134457}, issn = {1521-0758}, mesh = {Aged, 80 and over ; Asbestos, Amphibole/*adverse effects ; Female ; Humans ; Lung Neoplasms/*chemically induced ; Mesothelioma/*chemically induced ; Microscopy, Electron, Transmission ; }, abstract = {Mesothelioma is considered a signal tumor for exposure to asbestos (fibrous materials) and can occur decades after first exposure. The present case study reports on tissue burden of fibrous dust in a person who used a vermiculite material (Zonolite) as an attic insulator some 50 years prior to her death. The exposure occurred in two construction/renovation projects in her private residencies. She potentially had exposures to wall board/joint compounds during renovations. She additionally was reported to occasionally be involved in occupational activity, including drilling holes in presumed asbestos-containing electrical boxes. The tissue burden analysis revealed the presence of noncommercial amphibole asbestos fibers and consistent presence in the lung and lymph samples of Libby amphibole fibers. The findings of Libby amphibole fibers in human tissue can be attributed to exposure to Libby vermiculite. This study illustrates that analytical transmission electron microscopy can distinguish these structures from "asbestos" fibers. Further, the findings indicate that a population of these structures is biodurable and retained in the tissue years after first/last exposure.}, } @article {pmid24130165, year = {2014}, author = {Cleaver, AL and Bhamidipaty, K and Wylie, B and Connor, T and Robinson, C and Robinson, BW and Mutsaers, SE and Lake, RA}, title = {Long-term exposure of mesothelial cells to SV40 and asbestos leads to malignant transformation and chemotherapy resistance.}, journal = {Carcinogenesis}, volume = {35}, number = {2}, pages = {407-414}, doi = {10.1093/carcin/bgt322}, pmid = {24130165}, issn = {1460-2180}, mesh = {Animals ; Antigens, Polyomavirus Transforming/*toxicity ; Apoptosis/drug effects ; Asbestos, Crocidolite/*toxicity ; Blotting, Western ; Cell Adhesion/drug effects ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Cell Transformation, Neoplastic/genetics/metabolism/*pathology ; Cells, Cultured ; *Cocarcinogenesis ; *Drug Resistance, Neoplasm ; Humans ; Immunoenzyme Techniques ; Lung Neoplasms/genetics/metabolism/*pathology ; Mesothelioma/genetics/metabolism/*pathology ; Mesothelioma, Malignant ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Peritoneum/drug effects/metabolism/pathology ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {Simian virus 40 (SV40) has been implicated in the development of several cancers including malignant mesothelioma. A definitive role for the virus in human mesothelioma has not been unequivocally demonstrated but has been rigorously debated. The virus clearly has oncogenic potential: the TAg is one of the most potent transforming proteins known and acts synergistically with crocidolite asbestos to transform mesothelial cells. In this study, we show that SV40 oncogenes alone can cause malignant transformation and that asbestos-induced DNA damage and apoptosis occurs principally in cycling cells. After long-term exposure (up to 100 days) to both SV40 and asbestos, cells become resistant to stress-induced senescence. Significantly, these cells demonstrate resistance to chemotherapy-induced apoptosis. This finding has implications for the development of effective treatment options for patients with mesothelioma.}, } @article {pmid24128712, year = {2013}, author = {Zauderer, MG and Bott, M and McMillan, R and Sima, CS and Rusch, V and Krug, LM and Ladanyi, M}, title = {Clinical characteristics of patients with malignant pleural mesothelioma harboring somatic BAP1 mutations.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {8}, number = {11}, pages = {1430-1433}, pmid = {24128712}, issn = {1556-1380}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Germ-Line Mutation/*genetics ; Humans ; Lung Neoplasms/*genetics/pathology/therapy ; Male ; Mesothelioma/*genetics/pathology/therapy ; Mesothelioma, Malignant ; Middle Aged ; Neoplasm Staging ; Pleural Neoplasms/*genetics/pathology/therapy ; Prognosis ; Smoking/adverse effects ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {INTRODUCTION: Genomic studies of malignant pleural mesothelioma (MPM) have recently identified frequent mutations in the BRCA-associated protein 1(BAP1) gene. In uveal melanoma and clear cell renal cell carcinoma, BAP1 mutations are associated with poor outcomes but their clinical significance in MPM is unknown. We therefore undertook this study to define the characteristics of patients whose MPM tumors harbor somatic BAP1 mutation and to examine the relationship between BAP1 mutation and survival.

METHODS: We reviewed the charts of 121 patients with MPM tumors diagnosed between 1991 and 2009 tested for BAP1 mutation, and extracted the following information: age at diagnosis, sex, histology, stage, smoking status, asbestos exposure, family or personal history of malignancy, and treatment including surgery, chemotherapy, and radiation as well as survival status.

RESULTS: Twenty-four of the 121 tumors (20%) harbored somatic BAP1 mutations. The percentage of current or former smokers among cases with BAP1 mutations was significantly higher than in BAP1 wild-type cases, (75% versus 42%; p = 0.006). However, the types of nucleotide substitutions in BAP1 did not suggest that this association was because of a causative role of smoking in BAP1 mutations. No other clinical feature was significantly different among those with and without BAP1 mutations in their MPM. There was also no difference in survival according to somatic BAP1 mutation status.

CONCLUSION: There is no apparent distinct clinical phenotype for MPM with somatic BAP1 mutation. The significance of the more frequent history of smoking among patients with BAP1-mutated MPM warrants further study.}, } @article {pmid24124200, year = {2014}, author = {Sakai, K and Hisanaga, N and Shibata, E and Kamijima, M and Ichihara, G and Takeuchi, Y and Nakajima, T}, title = {Trends in asbestos and non-asbestos fibre concentrations in the lung tissues of Japanese patients with mesothelioma.}, journal = {The Annals of occupational hygiene}, volume = {58}, number = {1}, pages = {103-120}, doi = {10.1093/annhyg/met055}, pmid = {24124200}, issn = {1475-3162}, mesh = {Aged ; Asbestos/*analysis ; Carcinogens/*analysis ; Female ; Humans ; Japan ; Lung Neoplasms/*pathology ; Male ; Mesothelioma/*pathology ; Middle Aged ; Mineral Fibers/adverse effects/*analysis ; Occupational Diseases/*etiology/pathology ; Occupational Exposure/*adverse effects ; }, abstract = {OBJECTIVES: We aimed to elucidate changes in asbestos and non-asbestos fibre concentrations in the lung tissues of Japanese patients with mesothelioma over time.

METHODS: Lung tissues were obtained from 46 patients with mesothelioma who died or underwent surgery between 1971 and 2005. All of the patients had a history of occupational asbestos exposure. We classified patients into four groups according to the period during which their lung tissue was obtained. Asbestos and non-asbestos fibre concentrations were determined by transmission electron microscopy with energy-dispersive X-ray analysis using a low-temperature ashing procedure.

RESULTS: From the 1970s to the 2000s, we observed a decrease in the geometric mean of total asbestos concentration (67.4-1.05 million fibres per gram dry lung), chrysotile concentration (25.0-0.66 million fibres per gram dry lung), amphibole asbestos concentration (21.3-0.76 million fibres per gram dry lung), and non-asbestos fibre concentration (326-19.3 million fibres per gram dry lung). The mean duration of asbestos exposure decreased from 33.7 to 17.6 years, and the mean duration since the last exposure increased from 0.3 to 21.5 years. The percentage of longer fibres to total fibres tended to increase over time, whereas the mean fibre length did not differ significantly.

CONCLUSIONS: The present study suggested that asbestos and non-asbestos fibre concentrations in the lung tissues of Japanese patients with mesothelioma who have occupational histories of asbestos exposure may have decreased from the 1970s to the 2000s.}, } @article {pmid24108505, year = {2014}, author = {Järvholm, B and Englund, A}, title = {The impact of asbestos exposure in Swedish construction workers.}, journal = {American journal of industrial medicine}, volume = {57}, number = {1}, pages = {49-55}, doi = {10.1002/ajim.22264}, pmid = {24108505}, issn = {1097-0274}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Carcinogens/*toxicity ; *Construction Industry ; Humans ; Incidence ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Exposure/*adverse effects ; Occupations/statistics & numerical data ; Pleural Neoplasms/*epidemiology/etiology ; Prospective Studies ; Risk Factors ; Sweden/epidemiology ; Young Adult ; }, abstract = {OBJECTIVE: To study the occurrence of pleural mesothelioma as a measure of the impact on health from asbestos exposure in the construction industry.

METHODS: The occurrence of pleural mesothelioma in different occupations, time periods and birth cohorts was studied in a cohort of construction workers. They were prospectively followed after they had participated in health examinations between 1971 and 1993. The analysis was restricted to men and in total 367,568 men was included in the analysis.

RESULTS: In total there were 419 cases of pleural mesotheliomas between 1972 and 2009. As expected the age adjusted incidence was high in insulation workers and plumbers (39 and 16 cases per 100,000 person-years, respectively). However, only 21% of the pleural mesotheliomas occurred in those occupational groups. Occupational groups with many cases of pleural mesothelioma were concrete workers (N = 56), wood workers (N = 55), painters (N = 32), electricians (N = 48), and foremen (N = 37). The highest risk was in birth cohorts born between 1935 and 1945. Between 1995 and 2009 around one-third of all male cases in the country occurred in this birth cohort. The risk seemed to decrease considerably in men born after 1955.

CONCLUSION: In Sweden a considerable proportion of pleural mesotheliomas occur among construction workers; and not only in jobs traditionally associated with asbestos exposure such as insulators and plumbers but also among electricians, for example. The results shows that asbestos exposure occurs in many occupational groups, indicating that safe handling of asbestos is a very difficult or even impossible task in the construction industry.}, } @article {pmid24108494, year = {2014}, author = {Bang, KM and Mazurek, JM and Wood, JM and Hendricks, SA}, title = {Diseases attributable to asbestos exposure: years of potential life lost, United States, 1999-2010.}, journal = {American journal of industrial medicine}, volume = {57}, number = {1}, pages = {38-48}, pmid = {24108494}, issn = {1097-0274}, support = {CC999999//Intramural CDC HHS/United States ; }, mesh = {Adult ; Aged ; Asbestos/*toxicity ; Asbestosis/*mortality ; Cause of Death ; *Environmental Exposure ; Humans ; Life Expectancy/*trends ; Male ; Mesothelioma/etiology/*mortality ; Middle Aged ; *Occupational Exposure ; United States/epidemiology ; }, abstract = {BACKGROUND: Although asbestos use has been restricted in recent decades, asbestos-associated deaths continue to occur in the United States.

OBJECTIVES: We evaluated premature mortality and loss of potentially productive years of life attributable to asbestos-associated diseases.

METHODS: Using 1999-2010 National Center for Health Statistics mortality data, we identified decedents aged ≥25 years whose death certificate listed asbestosis and malignant mesothelioma as the underlying cause of death. We computed years of potential life lost to life expectancy (YPLL) and to age 65 (YPLL65).

RESULTS: During 1999-2010, a total of 427,005 YPLL and 55,184 YPLL65 were attributed to asbestosis (56,907 YPLL and 2,167 YPLL65), malignant mesothelioma (370,098 YPPL and 53,017 YPLL65). Overall and disease-specific asbestos-attributable total YPLL and YPLL65 and median YPLL and YPLL65 per decedent did not change significantly from 1999 to 2010.

CONCLUSIONS: The continuing occurrence of asbestos-associated diseases and their substantial premature mortality burden underscore the need for maintaining prevention efforts and for ongoing surveillance to monitor temporal trends in these diseases.}, } @article {pmid24107344, year = {2013}, author = {Takahashi, K and Ishii, Y}, title = {[Asbestos and the Industrial Safety and Health Law - in reference to the ordinance on prevention of hazards due to specified chemical substances and the ordinance on prevention of health impairment due to asbestos].}, journal = {Journal of UOEH}, volume = {35 Suppl}, number = {}, pages = {121-126}, doi = {10.7888/juoeh.35.121}, pmid = {24107344}, issn = {0387-821X}, mesh = {Asbestosis/*prevention & control ; Humans ; Occupational Health/*legislation & jurisprudence ; }, abstract = {Recently in Japan, mesothelioma and lung cancer caused by asbestos are increasing in number and in proportion among occupational cancers. It is thus obvious that asbestos will remain an important theme in the field of occupational health and safety. We hereby report on the relationship between asbestos and the Industrial Safety and Health Law, the Ordinance on Prevention of Hazards due to Specified Chemical Substances, and the Ordinance on Prevention of Health Impairment due to Asbestos, in reference to laws and regulations as well as official notifications issued by the Ministry. In particular, we will focus on the process by which our country totally prohibited the use of asbestos, countermeasures to prevent exposure of workers, historical changes regarding administrative concentration levels, and measures for the management of health of workers handling and dealing with asbestos.}, } @article {pmid24086716, year = {2013}, author = {Ishida, T and Alexandrov, M and Nishimura, T and Hirota, R and Ikeda, T and Kuroda, A}, title = {Molecular engineering of a fluorescent bioprobe for sensitive and selective detection of amphibole asbestos.}, journal = {PloS one}, volume = {8}, number = {9}, pages = {e76231}, pmid = {24086716}, issn = {1932-6203}, mesh = {Air Pollutants/*isolation & purification ; Asbestos, Amphibole/*isolation & purification/metabolism ; Binding Sites/genetics ; Bioengineering/*methods ; Biosensing Techniques/*methods ; Escherichia coli ; Escherichia coli Proteins/genetics/*metabolism ; Fimbriae Proteins/genetics/*metabolism ; Microscopy, Fluorescence/methods ; Protein Binding ; Sensitivity and Specificity ; Static Electricity ; Streptavidin/metabolism ; }, abstract = {Fluorescence microscopy-based affinity assay could enable highly sensitive and selective detection of airborne asbestos, an inorganic environmental pollutant that can cause mesothelioma and lung cancer. We have selected an Escherichia coli histone-like nucleoid structuring protein, H-NS, as a promising candidate for an amphibole asbestos bioprobe. H-NS has high affinity to amphibole asbestos, but also binds to an increasingly common asbestos substitute, wollastonite. To develop a highly specific Bioprobe for amphibole asbestos, we first identified a specific but low-affinity amosite-binding sequence by slicing H-NS into several fragments. Second, we constructed a streptavidin tetramer complex displaying four amosite-binding fragments, resulting in the 250-fold increase in the probe affinity as compared to the single fragment. The tetramer probe had sufficient affinity and specificity for detecting all the five types of asbestos in the amphibole group, and could be used to distinguish them from wollastonite. In order to clarify the binding mechanism and identify the amino acid residues contributing to the probe's affinity to amosite fibers, we constructed a number of shorter and substituted peptides. We found that the probable binding mechanism is electrostatic interaction, with positively charged side chains of lysine residues being primarily responsible for the probe's affinity to asbestos.}, } @article {pmid24084442, year = {2013}, author = {Alì, G and Borrelli, N and Riccardo, G and Proietti, A and Pelliccioni, S and Niccoli, C and Boldrini, L and Lucchi, M and Mussi, A and Fontanini, G}, title = {Differential expression of extracellular matrix constituents and cell adhesion molecules between malignant pleural mesothelioma and mesothelial hyperplasia.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {8}, number = {11}, pages = {1389-1395}, doi = {10.1097/JTO.0b013e3182a59f45}, pmid = {24084442}, issn = {1556-1380}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics/*metabolism ; Cell Adhesion Molecules/genetics/*metabolism ; Extracellular Matrix/genetics/*metabolism/pathology ; Female ; Follow-Up Studies ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Hyaluronan Receptors/genetics/metabolism ; Hyperplasia/genetics/*metabolism/pathology ; Immunoenzyme Techniques ; Integrin alpha3/genetics/metabolism ; Lung Neoplasms/genetics/*metabolism/pathology ; Male ; Matrix Metalloproteinase 14/genetics/metabolism ; Matrix Metalloproteinase 7/genetics/metabolism ; Mesothelioma/genetics/*metabolism/pathology ; Mesothelioma, Malignant ; Middle Aged ; Oligonucleotide Array Sequence Analysis ; Pleural Neoplasms/genetics/*metabolism/pathology ; Prognosis ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Retrospective Studies ; Reverse Transcriptase Polymerase Chain Reaction ; Young Adult ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is a highly aggressive neoplasm associated with asbestos exposure. Currently, the molecular mechanisms that induce MPM development are still unknown. The purpose of this study was to identify new molecular biomarkers for mesothelial carcinogenesis.

METHODS: We analyzed a panel of 84 genes involved in extracellular matrix remodeling and cell adhesion by polymerase chain reaction (PCR) array in 15 samples of epithelioid mesothelioma and 10 samples of reactive mesothelial hyperplasia (MH; 3 of 25 samples were inadequate for mRNA analysis). To validate the differentially expressed genes identified by PCR array, we analyzed 27 more samples by immunohistochemistry, in addition to the 25 samples already studied.

RESULTS: Twenty-five genes were differentially expressed in MPM and MH by PCR array. Of these we studied matrix metalloproteinase 7 (MMP7), MMP14, CD44, and integrin, alpha3 expression by immunohistochemistry in 26 epithelioid MPM and 26 MH samples from the entire series of 52 cases. We observed higher MMP14 and integrin, alpha3 expression in MPM samples compared with MH samples (p = 0.000002 and p = 0.000002, respectively). Conversely, CD44 expression was low in most (57.7%) mesothelioma samples but only in 11.5% of the MH samples (p = 0.0013). As regards MMP7, we did not observe differential expression between MH and MPM samples.

CONCLUSIONS: We have extensively studied genes involved in cell adhesion and extracellular matrix remodeling in MPM and MH samples, gaining new insight into the pathophysiology of mesothelioma. Moreover, our data suggest that these factors could be potential biomarkers for MPM.}, } @article {pmid24084028, year = {2013}, author = {Kagan, E}, title = {Asbestos-induced mesothelioma: is fiber biopersistence really a critical factor?.}, journal = {The American journal of pathology}, volume = {183}, number = {5}, pages = {1378-1381}, doi = {10.1016/j.ajpath.2013.09.005}, pmid = {24084028}, issn = {1525-2191}, mesh = {Animals ; Asbestos, Serpentine/*toxicity ; Cell Transformation, Neoplastic/*metabolism/*pathology ; Epithelium/*pathology ; HMGB1 Protein/*metabolism ; Humans ; Signal Transduction/*drug effects ; Tumor Necrosis Factor-alpha/*metabolism ; }, abstract = {This Commentary highlights the research by Qi et al detailing the similarities and differences between crocidolite and chrysotile asbestos in terms of their transcriptional effects and transforming actions in human mesothelial cells.}, } @article {pmid24083862, year = {2013}, author = {Bonde, JP}, title = {No indication that mineral wool causes mesothelioma.}, journal = {American journal of respiratory and critical care medicine}, volume = {188}, number = {7}, pages = {873}, doi = {10.1164/rccm.201304-0655LE}, pmid = {24083862}, issn = {1535-4970}, mesh = {Asbestos/*toxicity ; Calcium Compounds/*toxicity ; Humans ; Male ; Mesothelioma/*chemically induced ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*chemically induced ; Silicates/*toxicity ; Silicon Dioxide/*toxicity ; }, } @article {pmid24083861, year = {2013}, author = {Lacourt, A}, title = {Reply: No indication that mineral wool causes mesothelioma.}, journal = {American journal of respiratory and critical care medicine}, volume = {188}, number = {7}, pages = {873-874}, doi = {10.1164/rccm.201305-0901LE}, pmid = {24083861}, issn = {1535-4970}, mesh = {Asbestos/*toxicity ; Calcium Compounds/*toxicity ; Humans ; Male ; Mesothelioma/*chemically induced ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*chemically induced ; Silicates/*toxicity ; Silicon Dioxide/*toxicity ; }, } @article {pmid24081673, year = {2014}, author = {de Assis, LV and Isoldi, MC}, title = {The function, mechanisms, and role of the genes PTEN and TP53 and the effects of asbestos in the development of malignant mesothelioma: a review focused on the genes' molecular mechanisms.}, journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine}, volume = {35}, number = {2}, pages = {889-901}, pmid = {24081673}, issn = {1423-0380}, mesh = {Asbestos/*toxicity ; Carcinogens/toxicity ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Lung Neoplasms/chemically induced/*genetics/pathology/virology ; Membrane Proteins/*genetics/metabolism ; Mesothelioma/chemically induced/*genetics/pathology/virology ; Mesothelioma, Malignant ; PTEN Phosphohydrolase/*genetics/metabolism ; Simian virus 40/pathogenicity ; Tumor Suppressor Protein p53/*genetics/metabolism ; }, abstract = {The malignant mesothelioma is an aggressive form of cancer with a mean survival rate of less than a year. Moreover, environmental exposure to minerals is an important factor in the development of malignant mesothelioma (MM), especially the mineral asbestos, which has a well-documented role in MM, and more recently, the mineral erionite has been proven to be a strong carcinogenic inducer of MM. In addition, the virus simian virus 40 has been implicated as a co-carcinogenic player in MM. However, the molecular mechanisms involved in the pathogenesis of this cancer are still not fully understood. Indeed, it is known that several genes are altered or mutated in MM, among those are p16(INK4A), p14(ARF), and neurofibromatosis type II. Furthermore, TP53 has been reported to be mutated in the majority of the cancers; however, in MM, it is very uncommon mutations in this gene. Also, the PTEN gene has been shown to play an important role in endometrial cancer and glioblastoma, although the role of PTEN in MM has yet to be established. Taken altogether, this review focuses on the historical aspects, molecular mechanisms, interaction with other genes and proteins, and the role of these genes in MM. Lastly, this review questions the cancer theory of the two hits because the functions of both PTEN and TP53 are not fully explained by this theory.}, } @article {pmid24071603, year = {2013}, author = {Marsili, D and Comba, P}, title = {Asbestos case and its current implications for global health.}, journal = {Annali dell'Istituto superiore di sanita}, volume = {49}, number = {3}, pages = {249-251}, doi = {10.4415/ANN_13_03_03}, pmid = {24071603}, issn = {2384-8553}, mesh = {Asbestos ; Asbestosis/*prevention & control ; Humans ; Industry ; Italy ; Mesothelioma ; Occupational Exposure ; Public Health ; World Health Organization ; }, abstract = {Notwithstanding a major body of evidence on the carcinogenicity of all asbestos fibres and a general consensus of the scientific community on the health impact of this agent, asbestos is still produced and used in a large number of countries, thus determining further harm for future generations. Prevention of asbestos-related disease requires international cooperation, transfer of know-how and dissemination of successful procedures in order to contrast asbestos exposure in the frame of a global environmental health approach.}, } @article {pmid24066870, year = {2013}, author = {Stolnicu, S and Quiñonez, E and Boros, M and Molnar, C and Dulcey, I and Nogales, FF}, title = {Case report: Papillary mesothelioma of the peritoneum with foamy cell lining.}, journal = {Diagnostic pathology}, volume = {8}, number = {}, pages = {162}, pmid = {24066870}, issn = {1746-1596}, mesh = {Adult ; Asbestos/*adverse effects ; Biomarkers, Tumor/analysis ; Diagnosis, Differential ; Epithelial Cells/chemistry/*pathology ; Female ; Humans ; Immunohistochemistry ; Immunophenotyping ; Mesothelioma/chemistry/etiology/*pathology/surgery ; Peritoneal Neoplasms/chemistry/etiology/*pathology/surgery ; Predictive Value of Tests ; Treatment Outcome ; }, abstract = {UNLABELLED: A 34-year-old female, with a history of continued asbestos exposure, presented with a papillary peritoneal mesothelioma with a diffuse, prominent clear foamy cell change, with microvacuolation in its papillary lining, that expressed cytokeratins 7, 5/6 and calretinin as well as nuclear WT-1 and apical membrane staining for thrombomodulin, podoplanin D2-40 and HBME-1. In contrast, lining cells were CD68 negative. Foamy cell change has been reported in isolated cases as solid cords but not as a diffuse change in the mesothelial papillary lining. This phenomenon prompts differential diagnoses with abdominal and renal papillary clear cell tumours, which were discarded after a characteristic mesothelial immunophenotype was demonstrated.

VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4679576081031834.}, } @article {pmid24055913, year = {2013}, author = {Kassir, R and Forest, F and Kaczmarek, D}, title = {Pulmonary mucinous cystadenocarcinoma presenting as a pleural mesothelioma.}, journal = {International journal of surgery case reports}, volume = {4}, number = {11}, pages = {942-944}, pmid = {24055913}, issn = {2210-2612}, abstract = {INTRODUCTION: Primary Pulmonary Mucinous Cystadenocarcinoma PPMC is an extremely rare subtype of pulmonary adenocarcinoma, with only a few dozen cases reported in the literature to date.

PRESENTATION OF CASE: We report a extremely rare case of pulmonary mucinous cystadenocarcinoma presenting as a pleural mesothelioma. 53-year-old man exposed to asbestos, he is admitted in hospital with a 5cm mass in right pleura. He was treated by wedge resection. Sparse groups of malignant cells were microscopically observed in pools of mucin. The postoperative histopathological findings were in accordance with the diagnosis of pulmonary mucinous cystadenocarcinoma on cystic adenoid malformation of lung. 5 years later, the patient has no recurrence.

DISCUSSION: PPMC is usually asymptomatic; hemoptysis is seen occasionally. Preoperative diagnosis is very difficult to establish. Both FNA cytology and transbronchial lung biopsy seem inadequate. Our patient went on to undergo open lung biopsy and histopathological testing that confirmed the diagnosis of PMC.

CONCLUSION: It is important to differentiate this rare pathological feature of the lung from other lung tumors as the treatment is surgical rather than medical. Thoracic surgeons should bear in mind this rare tumor for the differential diagnosis of a pleural mesothelioma because this tumor has a favorable prognosis.}, } @article {pmid24050959, year = {2014}, author = {Giansanti, M and Bellezza, G and Guerriero, A and Pireddu, A and Sidoni, A}, title = {Localized Intrasplenic Mesothelioma: A Case Report.}, journal = {International journal of surgical pathology}, volume = {22}, number = {5}, pages = {451-455}, doi = {10.1177/1066896913503492}, pmid = {24050959}, issn = {1940-2465}, mesh = {Biomarkers, Tumor/metabolism ; Humans ; Incidental Findings ; Lung Neoplasms/diagnostic imaging/metabolism/*pathology ; Male ; Mesothelioma/diagnostic imaging/metabolism/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Splenic Neoplasms/diagnostic imaging/metabolism/*pathology ; Ultrasonography ; }, abstract = {Malignant mesothelioma is a primary neoplasm of the serosal membranes that usually presents with a diffuse pattern of growth. However, cases of localized mesotheliomas have been described. The predominant localization is the pleura; peritoneum and pericardium being rarer localizations. Only few cases of true intraparenchymal mesothelioma arising in organs such as liver, gonads, lung, and pancreas have been described. We report a case of an otherwise healthy 48-year-old man without asbestos exposure with a nodule of 3 cm in diameter, localized in the spleen, discovered incidentally at the ultrasonographic examination, for which histopathological and immunohistochemical findings were consistent with epithelioid mesothelioma: large round cells with eosinophil dense cytoplasm and macronucleoli and with immunohistochemical positivity for pancytokeratins, calretinin, Wilms tumor-1, and others markers of mesothelial differentiation. The diagnosis of localized intrasplenic epithelioid malignant mesothelioma was carried out. To the best of our knowledge, this is the first case of a localized intrasplenic mesothelioma published in the indexed literature.}, } @article {pmid24041698, year = {2013}, author = {Fox, SA and Richards, AK and Kusumah, I and Perumal, V and Bolitho, EM and Mutsaers, SE and Dharmarajan, AM}, title = {Expression profile and function of Wnt signaling mechanisms in malignant mesothelioma cells.}, journal = {Biochemical and biophysical research communications}, volume = {440}, number = {1}, pages = {82-87}, doi = {10.1016/j.bbrc.2013.09.025}, pmid = {24041698}, issn = {1090-2104}, mesh = {Cell Line, Tumor ; Cell Proliferation ; *Gene Expression Regulation, Neoplastic ; Humans ; Mesothelioma/*genetics/metabolism/pathology ; Pleura/metabolism/pathology ; Pleural Neoplasms/*genetics/metabolism/pathology ; Proto-Oncogene Proteins/genetics/metabolism ; Wnt Proteins/*genetics/metabolism ; *Wnt Signaling Pathway ; Wnt3 Protein/genetics/metabolism ; beta Catenin/genetics/metabolism ; }, abstract = {Malignant mesothelioma (MM) is an uncommon and particularly aggressive cancer associated with asbestos exposure, which currently presents an intractable clinical challenge. Wnt signaling has been reported to play a role in the neoplastic properties of mesothelioma cells but has not been investigated in detail in this cancer. We surveyed expression of Wnts, their receptors, and other key molecules in this pathway in well established in vitro mesothelioma models in comparison with primary mesothelial cultures. We also tested the biological response of MM cell lines to exogenous Wnt and secreted regulators, as well as targeting β-catenin. We detected frequent expression of Wnt3 and Wnt5a, as well as Fzd 2, 4 and 6. The mRNA of Wnt4, Fzd3, sFRP4, APC and axin2 were downregulated in MM relative to mesothelial cells while LEF1 was overexpressed in MM. Functionally, we observed that Wnt3a stimulated MM proliferation while sFRP4 was inhibitory. Furthermore, directly targeting β-catenin expression could sensitise MM cells to cytotoxic drugs. These results provide evidence for altered expression of a number of Wnt/Fzd signaling molecules in MM. Modulation of Wnt signaling in MM may prove a means of targeting proliferation and drug resistance in this cancer.}, } @article {pmid24033215, year = {2013}, author = {Park, EK and Yates, DH and Hyland, RA and Johnson, AR}, title = {Asbestos exposure during home renovation in New South Wales.}, journal = {The Medical journal of Australia}, volume = {199}, number = {6}, pages = {410-413}, doi = {10.5694/mja12.11802}, pmid = {24033215}, issn = {1326-5377}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Child ; Construction Materials/*adverse effects ; Cross-Sectional Studies ; *Housing ; Humans ; *Maintenance ; Middle Aged ; New South Wales ; Self Report ; Surveys and Questionnaires ; Young Adult ; }, abstract = {OBJECTIVE: Asbestos exposure is causally associated with the development of malignant mesothelioma (MM), which is increasingly being reported after exposure to asbestos fibro sheeting in Australia. In this study, we investigate self-reported non-occupational asbestos exposure during home renovation in New South Wales.

DESIGN AND SETTING: Cross-sectional mailed questionnaire examining renovation activity, tasks undertaken during renovation and self-reported exposure to asbestos among respondents and their family members in NSW between January and June 2008.

PARTICIPANTS: 10 000 adults aged 18-99 years, randomly selected from the NSW electoral roll. We received 3612 responses, while 365 questionnaires did not reach addressees, giving an overall response rate of 37.5%.

MAIN OUTCOME MEASURES: Differences in self-reported asbestos exposure between do-it-yourself (DIY) and non-DIY renovators.

RESULTS: 1597 participants (44.2%) had renovated their home and among these, 858 participants (53.7%) self-reported as DIY renovators. Of these, 527 (61.4%) reported asbestos exposure during home renovations, 337 (39.3%) reported that their partner had been exposed to asbestos during renovations, and 196 (22.8%) reported that their children had been exposed. More than 20% of renovators planned to further renovate their current homes within the next 5 years.

CONCLUSIONS: Self-reported asbestos exposure during home renovation is common. This preventable exposure could place adults and children at risk of MM many years into the future. Although such exposure is self-reported and ideally should be verified, this study identifies a potentially important problem in NSW.}, } @article {pmid24027648, year = {2013}, author = {Makarawate, P and Chaosuwannakit, N and Chindaprasirt, J and Ungarreevittaya, P and Chaiwiriyakul, S and Wirasorn, K and Kuptarnond, C and Sawanyawisuth, K}, title = {Malignant mesothelioma of the pericardium: a report of two different presentations.}, journal = {Case reports in oncological medicine}, volume = {2013}, number = {}, pages = {356901}, pmid = {24027648}, issn = {2090-6706}, abstract = {Malignant mesothelioma of the pericardium is a rare and fatal condition that clinicians should be aware of due to its variability of clinical manifestation. The diagnosis may be delayed as a result of delayed treatment. Here, we report two cases of malignant pericardial mesothelioma with two different clinical aspects: cardiac tamponade and mimic tuberculous pericarditis. Both patients: may have indirect exposure to asbestos. Despite chemotherapy, both patients died at 2 weeks and 3 months after the diagnosis. Malignant mesothelioma of the pericardium is fatal, has a variety of presentation, and may not be related to asbestosis exposure.}, } @article {pmid24027214, year = {2013}, author = {Nagai, H and Okazaki, Y and Chew, SH and Misawa, N and Yasui, H and Toyokuni, S}, title = {Deferasirox induces mesenchymal-epithelial transition in crocidolite-induced mesothelial carcinogenesis in rats.}, journal = {Cancer prevention research (Philadelphia, Pa.)}, volume = {6}, number = {11}, pages = {1222-1230}, doi = {10.1158/1940-6207.CAPR-13-0244}, pmid = {24027214}, issn = {1940-6215}, mesh = {Animals ; Asbestos, Crocidolite/*toxicity ; Benzoates/*toxicity ; Cell Transformation, Neoplastic/drug effects/*pathology ; Deferasirox ; Epithelial-Mesenchymal Transition/*drug effects ; Female ; Iron/*metabolism ; Iron Chelating Agents/*toxicity ; Male ; Mesothelioma/chemically induced/*pathology ; Phlebotomy ; Rats ; Spleen/drug effects/metabolism/pathology ; Triazoles/*toxicity ; }, abstract = {Asbestos was used worldwide in huge quantities in the past century. However, because of the unexpected carcinogenicity to mesothelial cells with an extremely long incubation period, many countries face this long-lasting social problem. Mesothelioma is often diagnosed in an advanced stage, for which no effective therapeutic protocols are yet established. We previously reported on the basis of animal experiments that the major pathology in asbestos-induced mesothelial carcinogenesis is local iron overload. Here, we undertook to find an effective strategy to prevent, delay, or lower the malignant potential of mesothelioma during asbestos-induced carcinogenesis. We used intraperitoneal injections of crocidolite to rats. We carried out a 16-week study to seek the maximal-tolerated intervention for iron reduction via oral deferasirox administration or intensive phlebotomy. Splenic iron deposition was significantly decreased with either method, and we found that Perls' iron staining in spleen is a good indicator for iron reduction. We injected a total of 10 mg crocidolite at the age of six weeks, and the preventive measures were via repeated oral administration of 25 to 50 mg/kg/d deferasirox or weekly to bimonthly phlebotomy of 4 to 10 mL/kg/d. The animals were observed until 110 weeks. Deferasirox administration significantly increased the fraction of less malignant epithelioid subtype. Although we found a slightly prolonged survival in deferasirox-treated female rats, larger sample size and refinement of the current protocol are necessary to deduce the cancer-preventive effects of deferasirox. Still, our results suggest deferasirox serves as a potential preventive strategy in people already exposed to asbestos via iron reduction.}, } @article {pmid24024776, year = {2013}, author = {Macura, SL and Steinbacher, JL and Macpherson, MB and Lathrop, MJ and Sayan, M and Hillegass, JM and Beuschel, SL and Perkins, TN and Spiess, PC and van der Vliet, A and Butnor, KJ and Shukla, A and Wadsworth, M and Landry, CC and Mossman, BT}, title = {Microspheres targeted with a mesothelin antibody and loaded with doxorubicin reduce tumor volume of human mesotheliomas in xenografts.}, journal = {BMC cancer}, volume = {13}, number = {}, pages = {400}, pmid = {24024776}, issn = {1471-2407}, support = {R41 CA126155/CA/NCI NIH HHS/United States ; T32 ES007122/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Antibodies, Monoclonal/*administration & dosage ; Body Weight ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Disease Models, Animal ; Doxorubicin/*administration & dosage ; *Drug Delivery Systems ; GPI-Linked Proteins/*antagonists & inhibitors/metabolism ; Humans ; Inflammation/metabolism/pathology ; Injections, Intraperitoneal ; Ki-67 Antigen/metabolism ; Macrophages/pathology ; Mesothelin ; Mesothelioma/drug therapy/*metabolism/*pathology ; Mice ; *Microspheres ; Necrosis/drug therapy ; Tumor Burden/drug effects ; Xenograft Model Antitumor Assays ; }, abstract = {BACKGROUND: Malignant mesotheliomas (MMs) are chemoresistant tumors related to exposure to asbestos fibers. The long latency period of MM (30-40 yrs) and heterogeneity of tumor presentation make MM difficult to diagnose and treat at early stages. Currently approved second-line treatments following surgical resection of MMs include a combination of cisplatin or carboplatin (delivered systemically) and pemetrexed, a folate inhibitor, with or without subsequent radiation. The systemic toxicities of these treatments emphasize the need for more effective, localized treatment regimens.

METHODS: Acid-prepared mesoporous silica (APMS) microparticles were loaded with doxorubicin (DOX) and modified externally with a mesothelin (MB) specific antibody before repeated intraperitoneal (IP) injections into a mouse xenograft model of human peritoneal MM. The health/weight of mice, tumor volume/weight, tumor necrosis and cell proliferation were evaluated in tumor-bearing mice receiving saline, DOX high (0.2 mg/kg), DOX low (0.05 mg/kg), APMS-MB, or APMS-MB-DOX (0.05 mg/kg) in saline.

RESULTS: Targeted therapy (APMS-MB-DOX at 0.05 mg/kg) was more effective than DOX low (0.05 mg/kg) and less toxic than treatment with DOX high (0.2 mg/kg). It also resulted in the reduction of tumor volume without loss of animal health and weight, and significantly decreased tumor cell proliferation. High pressure liquid chromatography (HPLC) of tumor tissue confirmed that APMS-MB-DOX particles delivered DOX to target tissue.

CONCLUSIONS: Data suggest that targeted therapy results in greater chemotherapeutic efficacy with fewer adverse side effects than administration of DOX alone. Targeted microparticles are an attractive option for localized drug delivery.}, } @article {pmid24010773, year = {2013}, author = {Mikami, K and Tabata, C and Tabata, R and Nogi, Y and Terada, T and Honda, M and Kamiya, H and Nishizaki, T and Nakano, T}, title = {Clinical significance of serum angiopoietin-1 in malignant peritoneal mesothelioma.}, journal = {Cancer investigation}, volume = {31}, number = {8}, pages = {511-515}, doi = {10.3109/07357907.2013.830734}, pmid = {24010773}, issn = {1532-4192}, mesh = {Angiopoietin-1/*blood ; Asbestos/toxicity ; Asbestosis/blood ; Environmental Exposure ; Female ; Humans ; Male ; Mesothelioma/*blood/epidemiology/*mortality ; Middle Aged ; Peritoneal Neoplasms/*blood/epidemiology/*mortality ; Pulmonary Fibrosis/complications ; Survival ; }, abstract = {We have previously reported that angiopoietin-1 was correlated with pulmonary fibrosis. Here, we investigated the serum levels of angiopoietin-1 in patients with malignant peritoneal mesothelioma, which originate from mesenchymal cells similar to lung fibroblasts. We showed that patients with peritoneal mesothelioma had significantly higher serum levels of angiopoietin-1 in comparison with a population with a history of asbestos exposure without peritoneal mesothelioma, and the Kaplan-Meier method revealed a significant correlation between serum angiopoietin-1 levels and survival. This is the first report about the relationship between angiopoietin-1 and peritoneal mesothelioma.}, } @article {pmid23989951, year = {2013}, author = {Frost, G}, title = {The latency period of mesothelioma among a cohort of British asbestos workers (1978-2005).}, journal = {British journal of cancer}, volume = {109}, number = {7}, pages = {1965-1973}, pmid = {23989951}, issn = {1532-1827}, mesh = {Adult ; Asbestos/*adverse effects ; Asbestosis/epidemiology/mortality ; Female ; Humans ; Lung Neoplasms/*epidemiology/mortality ; Male ; Mesothelioma/*epidemiology/mortality ; Middle Aged ; Occupational Diseases/epidemiology/mortality ; Occupational Exposure/*adverse effects ; Prospective Studies ; United Kingdom/epidemiology ; }, abstract = {BACKGROUND: The Great Britain (GB) Asbestos Survey is a prospective cohort of asbestos workers in GB. The objective of this study was to investigate determinants of mesothelioma latency, paying particular attention to indicators of intensity of asbestos exposure such as occupation, sex, and presence of asbestosis.

METHODS: The analysis included members of the cohort who died with mesothelioma between 1978 and 2005. The primary outcome was the latency period defined as the time from first occupational exposure to asbestos to death with mesothelioma. Generalised gamma accelerated failure-time models were used to estimate time ratios (TRs).

RESULTS: After excluding missing data, there were 614 workers who died with mesothelioma between 1978 and 2005. Total follow-up time was 9280 person-years, with a median latency of 22.8 years (95% confidence interval (CI) 16.0-27.2 years). In the fully adjusted model, latency was around 29% longer for females compared with males (TR=1.29, 95% CI=1.18-1.42), and 5% shorter for those who died with asbestosis compared with those who did not (TR=0.95, 95% CI=0.91-0.99). There was no evidence of an association between latency and occupation.

CONCLUSION: This study did not find sufficient evidence that greater intensity asbestos exposures would lead to shorter mesothelioma latencies.}, } @article {pmid23983468, year = {2013}, author = {Granieri, A and Tamburello, S and Tamburello, A and Casale, S and Cont, C and Guglielmucci, F and Innamorati, M}, title = {Quality of life and personality traits in patients with malignant pleural mesothelioma and their first-degree caregivers.}, journal = {Neuropsychiatric disease and treatment}, volume = {9}, number = {}, pages = {1193-1202}, pmid = {23983468}, issn = {1176-6328}, abstract = {Asbestos exposure causes significant pleural diseases, including malignant pleural mesothelioma (MPM). Taking into account the impact of MPM on emotional functioning and wellbeing, this study aimed to evaluate the quality of life and personality traits in patients with MPM and their first-degree caregivers through the World Health Organization Quality of Life-BREF (WHOQOL-BREF) and the Minnesota Multiphasic Personality Inventory-2 Restructured Form (MMPI-2-RF). The sample was composed of 27 MPM patients, 55 first-degree relatives enrolled in Casale Monferrato and Monfalcone (Italy), and 40 healthy controls (HC). Patients and relatives reported poorer physical health than the HC. Patients had a higher overall sense of physical debilitation and poorer health than relatives and the HC, more numerous complaints of memory problems and difficulties in concentrating, and a greater belief that goals cannot be reached or problems solved, while often claiming that they were more indecisive and inefficacious than the HC. First-degree relatives reported lower opinions of others, a greater belief that goals cannot be reached or problems solved, support for the notion that they are indecisive and inefficacious, and were more likely to suffer from fear that significantly inhibited normal activities than were HC. In multinomial regression analyses, partial models indicated that sex, physical comorbidities, and the True Response Inconsistency (TRIN-r), Malaise (MLS), and Behavior-Restricting Fears (BRF) dimensions of the MMPI-2-RF had significant effects on group differences. In conclusion, health care providers should assess the ongoing adjustment and emotional wellbeing of people with MPM and their relatives, and provide support to reduce emotional distress.}, } @article {pmid23982605, year = {2013}, author = {Meniawy, TM and Creaney, J and Lake, RA and Nowak, AK}, title = {Existing models, but not neutrophil-to-lymphocyte ratio, are prognostic in malignant mesothelioma.}, journal = {British journal of cancer}, volume = {109}, number = {7}, pages = {1813-1820}, pmid = {23982605}, issn = {1532-1827}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Biomarkers, Tumor ; Female ; Humans ; Leukocyte Count ; Lung Neoplasms/drug therapy/*mortality ; Lymphocyte Count ; Lymphocytes/*cytology ; Male ; Mesothelioma/drug therapy/*mortality ; Mesothelioma, Malignant ; Middle Aged ; Neutrophils/*cytology ; Prognosis ; Retrospective Studies ; Survival Rate ; }, abstract = {BACKGROUND: Recent studies proposed neutrophil-to-lymphocyte ratio (NLR) as a prognostic biomarker in malignant pleural mesothelioma (MPM). We examined baseline prognostic variables including NLR and the EORTC and CALGB models as predictors of overall survival (OS) in MPM.

METHODS: In this retrospective study, 274 consecutive eligible, newly presenting patients with MPM were included. Of these, 159 received chemotherapy, 10 had tri-modality therapy, 2 underwent surgery only and 103 received supportive care alone. Univariate analyses and multivariate Cox models were calculated for OS.

RESULTS: In univariate analysis, poor prognostic factors were: age ≥65 years, nonepithelioid histology, stage III-IV, poor performance status (PS), weight loss, chest pain, low haemoglobin and high platelet count. A baseline NLR≥ 5 did not predict worse OS (hazard ratio (HR) 1.25; P=0.122). On multivariate analysis, age, histology, PS, weight loss, chest pain and platelet count remained significant. The EORTC and CALGB prognostic groups were validated as predictive for OS (HR 1.62; P<0.001 and HR 1.65; P<0.001, respectively).

CONCLUSION: Our findings validate standard prognostic variables and the existing EORTC and CALGB models, but not NLR, at initial diagnosis of MPM. In guiding patient management at diagnosis, it is important to consider multiple baseline variables that jointly predict survival.}, } @article {pmid23977546, year = {2012}, author = {Linton, A and van Zandwijk, N and Reid, G and Clarke, S and Cao, C and Kao, S}, title = {Inflammation in malignant mesothelioma - friend or foe?.}, journal = {Annals of cardiothoracic surgery}, volume = {1}, number = {4}, pages = {516-522}, pmid = {23977546}, issn = {2225-319X}, } @article {pmid23977545, year = {2012}, author = {Nowak, AK}, title = {Chemotherapy for malignant pleural mesothelioma: a review of current management and a look to the future.}, journal = {Annals of cardiothoracic surgery}, volume = {1}, number = {4}, pages = {508-515}, pmid = {23977545}, issn = {2225-319X}, } @article {pmid23977542, year = {2012}, author = {Robinson, BM}, title = {Malignant pleural mesothelioma: an epidemiological perspective.}, journal = {Annals of cardiothoracic surgery}, volume = {1}, number = {4}, pages = {491-496}, pmid = {23977542}, issn = {2225-319X}, abstract = {This paper reviews the aetiology, distribution and projected future incidence of malignant mesothelioma. Asbestos exposure is the most thoroughly established risk factor. Debate continues regarding the relative importance of the different asbestos fibre types and the contribution of Simian virus 40 (SV40). Disease incidence varies markedly within and between countries. The highest annual rates of disease, approximately 30 case per million, are reported in Australia and Great Britain. The risk of disease increases with age and is higher in men. Time from asbestos exposure to disease diagnosis is on average greater than 40 years. Non-occupational asbestos exposures contribute an increasing proportion of disease. With the exception of the United States, incidence continues to increase. In developed countries peak incidence is expected to occur before 2030.}, } @article {pmid23977540, year = {2012}, author = {van Zandwijk, N and Reid, G and Linton, A and Kao, S}, title = {Radical surgery for malignant pleural mesothelioma: have we identified the appropriate selection tools?.}, journal = {Annals of cardiothoracic surgery}, volume = {1}, number = {4}, pages = {481-486}, pmid = {23977540}, issn = {2225-319X}, } @article {pmid23976967, year = {2013}, author = {Wright, CM and Kirschner, MB and Cheng, YY and O'Byrne, KJ and Gray, SG and Schelch, K and Hoda, MA and Klebe, S and McCaughan, B and van Zandwijk, N and Reid, G}, title = {Long non coding RNAs (lncRNAs) are dysregulated in Malignant Pleural Mesothelioma (MPM).}, journal = {PloS one}, volume = {8}, number = {8}, pages = {e70940}, pmid = {23976967}, issn = {1932-6203}, mesh = {Adult ; Aged ; Case-Control Studies ; Cell Line, Tumor ; Female ; Gene Expression Profiling ; Humans ; Lung Neoplasms/diagnosis/*genetics/mortality/pathology ; Male ; Mesothelioma/diagnosis/*genetics/mortality/pathology ; Mesothelioma, Malignant ; Middle Aged ; Oligonucleotide Array Sequence Analysis ; Pleural Neoplasms/diagnosis/*genetics/mortality/pathology ; RNA, Long Noncoding/*genetics ; ROC Curve ; Survival Analysis ; Up-Regulation ; }, abstract = {Malignant Pleural Mesothelioma (MPM) is an aggressive cancer that is often diagnosed at an advanced stage and is characterized by a long latency period (20-40 years between initial exposure and diagnosis) and prior exposure to asbestos. Currently accurate diagnosis of MPM is difficult due to the lack of sensitive biomarkers and despite minor improvements in treatment, median survival rates do not exceed 12 months. Accumulating evidence suggests that aberrant expression of long non-coding RNAs (lncRNAs) play an important functional role in cancer biology. LncRNAs are a class of recently discovered non-protein coding RNAs >200 nucleotides in length with a role in regulating transcription. Here we used NCode long noncoding microarrays to identify differentially expressed lncRNAs potentially involved in MPM pathogenesis. High priority candidate lncRNAs were selected on the basis of statistical (P<0.05) and biological significance (>3-fold difference). Expression levels of 9 candidate lncRNAs were technically validated using RT-qPCR, and biologically validated in three independent test sets: (1) 57 archived MPM tissues obtained from extrapleural pneumonectomy patients, (2) 15 cryopreserved MPM and 3 benign pleura, and (3) an extended panel of 10 MPM cell lines. RT-qPCR analysis demonstrated consistent up-regulation of these lncRNAs in independent datasets. ROC curve analysis showed that two candidates were able to separate benign pleura and MPM with high sensitivity and specificity, and were associated with nodal metastases and survival following induction chemotherapy. These results suggest that lncRNAs have potential to serve as biomarkers in MPM.}, } @article {pmid23974964, year = {2014}, author = {Serrier, H and Sultan-Taieb, H and Luce, D and Bejean, S}, title = {Estimating the social cost of respiratory cancer cases attributable to occupational exposures in France.}, journal = {The European journal of health economics : HEPAC : health economics in prevention and care}, volume = {15}, number = {6}, pages = {661-673}, pmid = {23974964}, issn = {1618-7601}, mesh = {Absenteeism ; *Cost of Illness ; Costs and Cost Analysis/economics/statistics & numerical data ; Female ; France/epidemiology ; Health Care Costs/statistics & numerical data ; Humans ; Laryngeal Neoplasms/economics/epidemiology/etiology/mortality ; Lung Neoplasms/economics/epidemiology/etiology/mortality ; Male ; Mesothelioma/economics/epidemiology/etiology/mortality ; Middle Aged ; Occupational Exposure/adverse effects/*economics ; Paranasal Sinus Neoplasms/economics/epidemiology/etiology/mortality ; Pleural Neoplasms/economics/epidemiology/etiology/mortality ; Respiratory Tract Neoplasms/*economics/epidemiology/etiology/mortality ; }, abstract = {PURPOSE: The objective of this article was to estimate the social cost of respiratory cancer cases attributable to occupational risk factors in France in 2010.

METHODS: According to the attributable fraction method and based on available epidemiological data from the literature, we estimated the number of respiratory cancer cases due to each identified risk factor. We used the cost-of-illness method with a prevalence-based approach. We took into account the direct and indirect costs. We estimated the cost of production losses due to morbidity (absenteeism and presenteeism) and mortality costs (years of production losses) in the market and nonmarket spheres.

RESULTS: The social cost of lung, larynx, sinonasal and mesothelioma cancer caused by exposure to asbestos, chromium, diesel engine exhaust, paint, crystalline silica, wood and leather dust in France in 2010 were estimated at between 917 and 2,181 million euros. Between 795 and 2,011 million euros (87-92%) of total costs were due to lung cancer alone. Asbestos was by far the risk factor representing the greatest cost to French society in 2010 at between 531 and 1,538 million euros (58-71%), ahead of diesel engine exhaust, representing an estimated social cost of between 233 and 336 million euros, and crystalline silica (119-229 million euros). Indirect costs represented about 66% of total costs.

CONCLUSION: Our assessment shows the magnitude of the economic impact of occupational respiratory cancers. It allows comparisons between countries and provides valuable information for policy-makers responsible for defining public health priorities.}, } @article {pmid23963927, year = {2014}, author = {Arzt, L and Quehenberger, F and Halbwedl, I and Mairinger, T and Popper, HH}, title = {BAP1 protein is a progression factor in malignant pleural mesothelioma.}, journal = {Pathology oncology research : POR}, volume = {20}, number = {1}, pages = {145-151}, pmid = {23963927}, issn = {1532-2807}, mesh = {Asbestos/adverse effects ; Disease Progression ; Female ; Humans ; Immunohistochemistry/methods ; Lung Neoplasms/*genetics/*pathology ; Male ; Mesothelioma/*genetics/*pathology ; Mesothelioma, Malignant ; Mutation ; Pleural Neoplasms/*genetics/*pathology ; Prognosis ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {Human malignant pleural mesothelioma (MPM) is an aggressive cancer due to former asbestos exposure with little knowledge about prognostic factors of outcome and resistance to conventional therapy. BRCA1-associated protein 1 (BAP1) is a tumor suppressor gene that is frequently lost in MPM. Germline mutations of BAP1 predispose to several different tumors including malignant mesothelioma. Our study aimed to clarify if asbestos exposure has an influence on BAP1 expression and if BAP1 expression could be used as a prognostic factor of outcome. An immunohistochemical staining for BAP1 was performed on 123 MPM tissue samples and the expression levels have been correlated with asbestos exposure and overall survival time. BAP1 expression was not associated with asbestos exposure but we detected a significant effect of BAP1 expression on overall survival time--the higher the BAP1 expression (non-mutated BAP1), the shorter the overall survival. BAP1 mutation has been linked to non-asbestos induced familial mesotheliomas, which usually belong to the long survivor group and BAP1 is most probably functioning differently than in sporadic cases. Further investigations need to be performed to characterize the BAP1 mutations and to identify the BAP1 downstream targets in MPM.}, } @article {pmid23961336, year = {2013}, author = {Pham, VH and Lan Tran, TN and Le, GV and Movahed, M and Jiang, Y and Pham, NH and Ogawa, H and Takahashi, K}, title = {Asbestos and Asbestos-related Diseases in Vietnam: In reference to the International Labor Organization/World Health Organization National Asbestos Profile.}, journal = {Safety and health at work}, volume = {4}, number = {2}, pages = {117-121}, pmid = {23961336}, issn = {2093-7911}, abstract = {This paper describes progress on formulating a national asbestos profile for the country of Vietnam. The Center of Asbestos Resource, Vietnam, formulated a National Profile on Asbestos-related Occupational Health, with due reference to the International Labor Organization/World Health Organization National Asbestos Profile. The Center of Asbestos Resource was established by the Vietnamese Health Environment Management Agency and the National Institute of Labor Protection, with the support of the Australian Agency for International Development, as a coordinating point for asbestos-related issues in Vietnam. Under the National Profile on Asbestos-related Occupational Health framework, the Center of Asbestos Resource succeeded in compiling relevant information for 15 of the 18 designated items outlined in the International Labor Organization/World Health Organization National Asbestos Profile, some overlaps of the information items notwithstanding. Today, Vietnam continues to import and use an average of more than 60,000 metric tons of raw asbestos per year. Information on asbestos-related diseases is limited, but the country has begun to diagnose mesothelioma cases, with the technical cooperation of Japan. As it stands, the National Profile on Asbestos-related Occupational Health needs further work and updating. However, we envisage that the National Profile on Asbestos-related Occupational Health will ultimately facilitate the smooth transition to an asbestos-free Vietnam.}, } @article {pmid23959774, year = {2014}, author = {Thompson, JK and Westbom, CM and Shukla, A}, title = {Malignant mesothelioma: development to therapy.}, journal = {Journal of cellular biochemistry}, volume = {115}, number = {1}, pages = {1-7}, pmid = {23959774}, issn = {1097-4644}, support = {R01 ES021110/ES/NIEHS NIH HHS/United States ; 1R01 ES021110/ES/NIEHS NIH HHS/United States ; }, mesh = {Asbestos/*toxicity ; Humans ; Lung Neoplasms/chemically induced/diagnosis/*etiology/pathology/*therapy ; Mesothelioma/chemically induced/diagnosis/*etiology/pathology/*therapy ; Mesothelioma, Malignant ; Molecular Targeted Therapy ; }, abstract = {Malignant mesothelioma (MM) is an aggressive cancer of the mesothelium caused by asbestos. Asbestos use has been reduced but not completely stopped. In addition, natural or man-made disasters will continue to dislodge asbestos from old buildings into the atmosphere and as long as respirable asbestos is available, MM will continue to be a threat. Due to the long latency period of MM development, it would still take decades to eradicate this disease if asbestos was completely removed from our lives today. Therefore, there is a need for researchers and clinicians to work together to understand this deadly disease and find a solution for early diagnosis and treatment. This article focuses on developmental mechanisms as well as current therapies available for MM.}, } @article {pmid23956266, year = {2013}, author = {Andrews, W and Paul, S and Narula, N and Altorki, NK}, title = {Localized mesothelioma tumour arising synchronously with a primary contralateral lung cancer.}, journal = {Interactive cardiovascular and thoracic surgery}, volume = {17}, number = {6}, pages = {1061-1062}, pmid = {23956266}, issn = {1569-9285}, mesh = {Adenocarcinoma/chemistry/*pathology/surgery ; Adenocarcinoma of Lung ; Aged, 80 and over ; Biomarkers, Tumor/analysis ; Biopsy ; Carcinoma, Non-Small-Cell Lung/chemistry/*pathology/surgery ; Humans ; Lung Neoplasms/chemistry/*pathology/surgery ; Male ; Mesothelioma/chemistry/*pathology/surgery ; *Neoplasms, Multiple Primary ; Pleural Neoplasms/chemistry/*pathology/surgery ; Pneumonectomy/methods ; Thoracic Surgery, Video-Assisted ; Thoracotomy ; Tomography, X-Ray Computed ; Treatment Outcome ; }, abstract = {Mesothelioma is a malignant growth of mesothelial cells found in the serosal membrane of pleural, peritoneal and pericardial surfaces as a result of prolonged exposure to asbestos. Malignant pleural mesothelioma (MPM) typically presents itself in a diffuse pattern of growth over the pleura of the lung or in more rare cases as a localized focus (LMPM). We present the first reported case of a synchronous LMPM and non-small adenocarcinoma of the lung treated by sequential resections.}, } @article {pmid23953740, year = {2013}, author = {Baadh, AS and Xiong, X and Singh, S and Kapoor, R and Zhou, J and Katz, DS}, title = {Radiology-pathology conference: primary peritoneal mesothelioma.}, journal = {Clinical imaging}, volume = {37}, number = {6}, pages = {1142-1145}, doi = {10.1016/j.clinimag.2013.07.009}, pmid = {23953740}, issn = {1873-4499}, mesh = {Aged ; Asbestos/toxicity ; Fatal Outcome ; Humans ; Liver/diagnostic imaging/*pathology ; Male ; Mesothelioma/diagnostic imaging/etiology/*pathology ; Neoplasm Invasiveness ; Peritoneal Neoplasms/diagnostic imaging/etiology/*pathology ; Prognosis ; Smoking/adverse effects ; Tomography, X-Ray Computed ; }, abstract = {Primary peritoneal mesothelioma is a rare neoplasm which carries a dismal prognosis. These highly aggressive tumors arise from mesothelial cells lining the peritoneum and are rapidly fatal. The neoplasm is typically associated with crocidolite asbestos exposure. We present the case of a 75-year-old man with primary peritoneal mesothelioma, with invasion into the right hepatic lobe.}, } @article {pmid23953254, year = {2014}, author = {Bourgault, MH and Gagné, M and Valcke, M}, title = {Lung cancer and mesothelioma risk assessment for a population environmentally exposed to asbestos.}, journal = {International journal of hygiene and environmental health}, volume = {217}, number = {2-3}, pages = {340-346}, doi = {10.1016/j.ijheh.2013.07.008}, pmid = {23953254}, issn = {1618-131X}, mesh = {Asbestos/*adverse effects ; Humans ; Inhalation Exposure/*adverse effects ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Mining ; Particulate Matter/*adverse effects ; Prospective Studies ; Quebec/epidemiology ; Risk ; Risk Assessment ; }, abstract = {Asbestos-related cancer risk is usually a concern restricted to occupational settings. However, recent published data on asbestos environmental concentrations in Thetford Mines, a mining city in Quebec, Canada, provided an opportunity to undertake a prospective cancer risk assessment in the general population exposed to these concentrations. Using an updated Berman and Crump dose-response model for asbestos exposure, we selected population-specific potency factors for lung cancer and mesothelioma. These factors were evaluated on the basis of population-specific cancer data attributed to the studied area's past environmental levels of asbestos. We also used more recent population-specific mortality data along with the validated potency factors to generate corresponding inhalation unit risks. These unit risks were then combined with recent environmental measurements made in the mining town to calculate estimated lifetime risk of asbestos-induced lung cancer and mesothelioma. Depending on the chosen potency factors, the lifetime mortality risks varied between 0.7 and 2.6 per 100,000 for lung cancer and between 0.7 and 2.3 per 100,000 for mesothelioma. In conclusion, the estimated lifetime cancer risk for both cancers combined is close to Health Canada's threshold for "negligible" lifetime cancer risks. However, the risks estimated are subject to several uncertainties and should be confirmed by future mortality rates attributed to present day asbestos exposure.}, } @article {pmid23940847, year = {2013}, author = {Heederik, D and Lenters, V and Vermeulen, R}, title = {Reply: response to the letter by Drs Berman and Case.}, journal = {The Annals of occupational hygiene}, volume = {57}, number = {5}, pages = {675-677}, doi = {10.1093/annhyg/met017}, pmid = {23940847}, issn = {1475-3162}, mesh = {*Asbestos ; Humans ; Mesothelioma/*chemically induced ; Research/*standards ; Risk Assessment/*standards ; }, } @article {pmid23939988, year = {2013}, author = {Camiade, E and Gramond, C and Jutand, MA and Audignon, S and Rinaldo, M and Imbernon, E and Luce, D and Galateau-Sallé, F and Astoul, P and Pairon, JC and Brochard, P and Lacourt, A}, title = {Characterization of a French series of female cases of mesothelioma.}, journal = {American journal of industrial medicine}, volume = {56}, number = {11}, pages = {1307-1316}, doi = {10.1002/ajim.22229}, pmid = {23939988}, issn = {1097-0274}, mesh = {Aged ; Asbestos/*poisoning ; *Carcinogens ; Causality ; Environmental Exposure/statistics & numerical data ; Female ; France/epidemiology ; Humans ; Mesothelioma/*epidemiology ; Middle Aged ; Neoplasms, Radiation-Induced/*epidemiology ; Occupational Diseases/*epidemiology ; Occupational Exposure/*statistics & numerical data ; Pleural Neoplasms/*epidemiology ; Radiotherapy/adverse effects ; Retrospective Studies ; Risk Factors ; X-Rays/adverse effects ; }, abstract = {BACKGROUND: More than 80% of mesothelioma cases in men are attributable to occupational asbestos exposure compared to only 40% in women. The objective of the study was to characterize a series of female pleural mesotheliomas according to known and suspected risk factors.

METHODS: From the exhaustive recording of 318 female mesothelioma cases in the French National Mesothelioma Surveillance Program between 1998 and 2009, multiple correspondence analysis and hybrid clustering were performed to characterize these cases according to expert assessed occupational and non-occupational exposure to asbestos and man-made vitreous fibers, X-ray exposure, and history of cancer and non-malignant respiratory diseases.

RESULTS: Four clusters were identified: (1) occupational exposure to asbestos and man-made vitreous fibers (7.9% of subjects); (2) radiation exposure during radiotherapy (12.9%); (3) increased asbestos exposure (19.8%); and (4) "non-exposure" characteristics (59.4%).

CONCLUSION: These results will allow hypotheses to be generated about associations between mesothelioma and non-occupational asbestos exposure, X-ray exposure and history of respiratory disease.}, } @article {pmid23937860, year = {2013}, author = {Hillegass, JM and Miller, JM and MacPherson, MB and Westbom, CM and Sayan, M and Thompson, JK and Macura, SL and Perkins, TN and Beuschel, SL and Alexeeva, V and Pass, HI and Steele, C and Mossman, BT and Shukla, A}, title = {Asbestos and erionite prime and activate the NLRP3 inflammasome that stimulates autocrine cytokine release in human mesothelial cells.}, journal = {Particle and fibre toxicology}, volume = {10}, number = {}, pages = {39}, pmid = {23937860}, issn = {1743-8977}, support = {R01 ES021110/ES/NIEHS NIH HHS/United States ; T32 ES007122/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Asbestos, Crocidolite/*toxicity ; *Autocrine Communication ; Carrier Proteins/*metabolism ; Cell Line, Tumor ; Cytokines/genetics/*metabolism ; Dose-Response Relationship, Drug ; Epithelium/*drug effects/immunology/pathology ; Humans ; Inflammasomes/*drug effects/immunology ; Inflammation Mediators/*metabolism ; Interleukin 1 Receptor Antagonist Protein/pharmacology ; Mesothelioma/*chemically induced/drug therapy/genetics/immunology/pathology ; Mice ; Mice, SCID ; NLR Family, Pyrin Domain-Containing 3 Protein ; Primary Cell Culture ; RNA, Messenger/metabolism ; Receptors, Interleukin-1/antagonists & inhibitors/metabolism ; Time Factors ; Transcription, Genetic/drug effects ; Xenograft Model Antitumor Assays ; Zeolites/*toxicity ; }, abstract = {BACKGROUND: Pleural fibrosis and malignant mesotheliomas (MM) occur after exposures to pathogenic fibers, yet the mechanisms initiating these diseases are unclear.

RESULTS: We document priming and activation of the NLRP3 inflammasome in human mesothelial cells by asbestos and erionite that is causally related to release of IL-1β, IL-6, IL-8, and Vascular Endothelial Growth Factor (VEGF). Transcription and release of these proteins are inhibited in vitro using Anakinra, an IL-1 receptor antagonist that reduces these cytokines in a human peritoneal MM mouse xenograft model.

CONCLUSIONS: These novel data show that asbestos-induced priming and activation of the NLRP3 inflammasome triggers an autocrine feedback loop modulated via the IL-1 receptor in mesothelial cell type targeted in pleural infection, fibrosis, and carcinogenesis.}, } @article {pmid23937772, year = {2013}, author = {Schuberth, PC and Hagedorn, C and Jensen, SM and Gulati, P and van den Broek, M and Mischo, A and Soltermann, A and Jüngel, A and Marroquin Belaunzaran, O and Stahel, R and Renner, C and Petrausch, U}, title = {Treatment of malignant pleural mesothelioma by fibroblast activation protein-specific re-directed T cells.}, journal = {Journal of translational medicine}, volume = {11}, number = {}, pages = {187}, pmid = {23937772}, issn = {1479-5876}, mesh = {Adoptive Transfer ; Animals ; Antigens, CD/metabolism ; Antigens, Neoplasm/metabolism ; CD8-Positive T-Lymphocytes/immunology ; Cell Line ; Cytotoxicity, Immunologic ; Endopeptidases ; Gelatinases/*metabolism ; Humans ; Immunohistochemistry ; *Immunotherapy ; Lung Neoplasms/*immunology/*therapy ; Membrane Proteins/*metabolism ; Mesothelioma/*immunology/*therapy ; Mesothelioma, Malignant ; Mice ; Peritoneum/pathology ; Pleural Neoplasms/*immunology/*therapy ; Recombinant Proteins/metabolism ; Serine Endopeptidases/*metabolism ; Stromal Cells/metabolism ; T-Lymphocytes/*immunology/metabolism ; Transduction, Genetic ; Xenograft Model Antitumor Assays ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is an incurable malignant disease, which results from chronic exposition to asbestos in at least 70% of the cases. Fibroblast activation protein (FAP) is predominantly expressed on the surface of reactive tumor-associated fibroblasts as well as on particular cancer types. Because of its expression on the cell surface, FAP is an attractive target for adoptive T cell therapy. T cells can be re-directed by retroviral transfer of chimeric antigen receptors (CAR) against tumor-associated antigens (TAA) and therefore represent a therapeutic strategy of adoptive immunotherapy.

METHODS: To evaluate FAP expression immunohistochemistry was performed in tumor tissue from MPM patients. CD8+ human T cells were retrovirally transduced with an anti-FAP-F19-∆CD28/CD3ζ-CAR. T cell function was evaluated in vitro by cytokine release and cytotoxicity assays. In vivo function was tested with an intraperitoneal xenograft tumor model in immunodeficient mice.

RESULTS: FAP was found to be expressed in all subtypes of MPM. Additionally, FAP expression was evaluated in healthy adult tissue samples and was only detected in specific areas in the pancreas, the placenta and very weakly for cervix and uterus. Expression of the anti-FAP-F19-∆CD28/CD3ζ-CAR in CD8+ T cells resulted in antigen-specific IFNγ release. Additionally, FAP-specific re-directed T cells lysed FAP positive mesothelioma cells and inflammatory fibroblasts in an antigen-specific manner in vitro. Furthermore, FAP-specific re-directed T cells inhibited the growth of FAP positive human tumor cells in the peritoneal cavity of mice and significantly prolonged survival of mice.

CONCLUSION: FAP re-directed CD8+ T cells showed antigen-specific functionality in vitro and in vivo. Furthermore, FAP expression was verified in all MPM histotypes. Therefore, our data support performing a phase I clinical trial in which MPM patients are treated with adoptively transferred FAP-specific re-directed T cells.}, } @article {pmid23932389, year = {2013}, author = {Niccoli-Asabella, A and Notaristefano, A and Rubini, D and Altini, C and Ferrari, C and Merenda, N and Fanelli, M and Rubini, G}, title = {18F-FDG PET/CT in suspected recurrences of epithelial malignant pleural mesothelioma in asbestos-fibers-exposed patients (comparison to standard diagnostic follow-up).}, journal = {Clinical imaging}, volume = {37}, number = {6}, pages = {1098-1103}, doi = {10.1016/j.clinimag.2013.06.009}, pmid = {23932389}, issn = {1873-4499}, mesh = {Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Environmental Exposure ; Female ; *Fluorodeoxyglucose F18 ; Follow-Up Studies ; Humans ; Lung Neoplasms/*diagnosis/diagnostic imaging ; Lymph Nodes/diagnostic imaging ; Male ; Mesothelioma/*diagnosis/diagnostic imaging ; Mesothelioma, Malignant ; Middle Aged ; Neoplasm Recurrence, Local/*diagnosis/diagnostic imaging ; Occupational Exposure ; Pleural Neoplasms/*diagnosis/diagnostic imaging ; Positron-Emission Tomography/*methods ; Respiratory Mucosa/diagnostic imaging/pathology ; Retrospective Studies ; Tomography, X-Ray Computed/*methods ; }, abstract = {This retrospective study evaluated the role of 18-fluorine-labeled 2-deoxy-2-fluoro-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) in patients with previous occupational or environmental exposure to asbestos, with histopathological diagnosis of epithelial malignant pleural mesothelioma and suspected recurrences, comparing the data from 18F-FDG PET/CT and computed tomography with contrast enhancement (CECT). 18F-FDG PET/CT has greater sensitivity than CECT in identifying local extent, lymph nodes, and metastasis. 18F-FDG PET/CT whole-body explorations are useful to monitor the follow-up and evaluate the metabolic response to chemo- and radiotherapy, modifying the scheduled treatment plan.}, } @article {pmid23924264, year = {2013}, author = {Lohcharoenkal, W and Wang, L and Stueckle, TA and Dinu, CZ and Castranova, V and Liu, Y and Rojanasakul, Y}, title = {Chronic exposure to carbon nanotubes induces invasion of human mesothelial cells through matrix metalloproteinase-2.}, journal = {ACS nano}, volume = {7}, number = {9}, pages = {7711-7723}, pmid = {23924264}, issn = {1936-086X}, support = {P20 RR016440/RR/NCRR NIH HHS/United States ; R01 HL095579/HL/NHLBI NIH HHS/United States ; P30 RR032138/RR/NCRR NIH HHS/United States ; R01-HL095579/HL/NHLBI NIH HHS/United States ; P20 RR016477/RR/NCRR NIH HHS/United States ; P30 GM103488/GM/NIGMS NIH HHS/United States ; }, mesh = {Cell Line ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Cell Transformation, Neoplastic/drug effects/*metabolism ; Cells, Cultured ; Dose-Response Relationship, Drug ; Epithelial Cells/*drug effects/*pathology ; Humans ; Matrix Metalloproteinase 2/*metabolism ; Mesothelioma/*chemically induced/*pathology ; Nanotubes, Carbon/*toxicity ; Neoplasm Invasiveness ; }, abstract = {Malignant mesothelioma is one of the most aggressive forms of cancer known. Recent studies have shown that carbon nanotubes (CNTs) are biopersistent and induce mesothelioma in animals, but the underlying mechanisms are not known. Here, we investigate the effect of long-term exposure to high aspect ratio CNTs on the aggressive behaviors of human pleural mesothelial cells, the primary cellular target of human lung mesothelioma. We show that chronic exposure (4 months) to single- and multiwalled CNTs induced proliferation, migration, and invasion of the cells similar to that observed in asbestos-exposed cells. An up-regulation of several key genes known to be important in cell invasion, notably matrix metalloproteinase-2 (MMP-2), was observed in the exposed mesothelial cells as determined by real-time PCR. Western blot and enzyme activity assays confirmed the increased expression and activity of MMP-2. Whole genome microarray analysis further indicated the importance of MMP-2 in the invasion gene signaling network of the exposed cells. Knockdown of MMP-2 in CNT and asbestos-exposed cells by shRNA-mediated gene silencing effectively inhibited the aggressive phenotypes. This study demonstrates CNT-induced cell invasion and indicates the role of MMP-2 in the process.}, } @article {pmid23917077, year = {2014}, author = {Chew, SH and Okazaki, Y and Nagai, H and Misawa, N and Akatsuka, S and Yamashita, K and Jiang, L and Yamashita, Y and Noguchi, M and Hosoda, K and Sekido, Y and Takahashi, T and Toyokuni, S}, title = {Cancer-promoting role of adipocytes in asbestos-induced mesothelial carcinogenesis through dysregulated adipocytokine production.}, journal = {Carcinogenesis}, volume = {35}, number = {1}, pages = {164-172}, doi = {10.1093/carcin/bgt267}, pmid = {23917077}, issn = {1460-2180}, mesh = {3T3-L1 Cells ; Adipocytes/metabolism/*pathology ; Adipokines/metabolism ; Adipose Tissue/drug effects/metabolism ; Animals ; Asbestos/pharmacokinetics/*toxicity ; Chemokine CCL2/genetics/metabolism ; Gene Expression Regulation/drug effects ; Humans ; Lung Neoplasms/*chemically induced/*pathology ; Male ; Mesothelioma/*chemically induced/*pathology ; Mesothelioma, Malignant ; Mice ; Mice, Inbred Strains ; }, abstract = {Like many other human cancers, the development of malignant mesothelioma is closely associated with a chronic inflammatory condition. Both macrophages and mesothelial cells play crucial roles in the inflammatory response caused by asbestos exposure. Here, we show that adipocytes can also contribute to asbestos-induced inflammation through dysregulated adipocytokine production. 3T3-L1 preadipocytes were differentiated into mature adipocytes prior to use. These cells took up asbestos fibers (chrysotile, crocidolite and amosite) but were more resistant to asbestos-induced injury than macrophages and mesothelial cells. Expression microarray analysis followed by reverse transcription-PCR revealed that adipocytes respond directly to asbestos exposure with an increased production of proinflammatory adipocytokines [e.g. monocyte chemoattractant protein-1 (MCP-1)], whereas the production of anti-inflammatory adipocytokines (e.g. adiponectin) is suppressed. This was confirmed in epididymal fat pad of mice after intraperitoneal injection of asbestos fibers. Such dysregulated adipocytokine production favors the establishment of a proinflammatory environment. Furthermore, MCP-1 marginally promoted the growth of MeT-5A mesothelial cells and significantly enhanced the wound healing of Y-MESO-8A and Y-MESO-8D human mesothelioma cells. Our results suggest that increased levels of adipocytokines, such as MCP-1, can potentially contribute to the promotion of mesothelial carcinogenesis through the enhanced recruitment of inflammatory cells as well as a direct growth and migration stimulatory effect on mesothelial and mesothelioma cells. Taken together, our findings support a potential cancer-promoting role of adipocytes in asbestos-induced mesothelial carcinogenesis.}, } @article {pmid23915043, year = {2013}, author = {Rosell-Murphy, MI and Abós-Herràndiz, R and Olivella, JT and Alberti-Casas, C and Allas, IG and Artés, XM and Günther, IK and Malet, IG and Martínez, RO and Canela-Soler, J}, title = {Risk factors associated with asbestos-related diseases: a community-based case-control study.}, journal = {BMC public health}, volume = {13}, number = {}, pages = {723}, pmid = {23915043}, issn = {1471-2458}, mesh = {Adult ; Analysis of Variance ; Asbestos/adverse effects ; Asbestosis/*epidemiology/prevention & control ; Case-Control Studies ; Cohort Studies ; Female ; Humans ; Incidence ; Lung Neoplasms/*epidemiology/prevention & control ; Male ; Mesothelioma/*epidemiology/prevention & control ; Mesothelioma, Malignant ; Occupational Exposure/statistics & numerical data ; *Research Design ; Residence Characteristics ; Risk ; Risk Factors ; Spain ; }, abstract = {BACKGROUND: Asbestos is a first level carcinogen. However, few epidemiological studies analyse the risk and protective factors associated with asbestos-related diseases and follow up these conditions in the general population. Pleural mesothelioma, caused by inhalation of asbestos fibres at work, at home or in the environment, is the most representative asbestos-related disease.The objectives of this study are to analyse the risk and protective factors associated with asbestos-related diseases and to investigate the incidence of new clinical manifestations in patients already diagnosed with some form of ARD.

METHODS/DESIGN: We have designed a matched case-control study with follow up of both cohorts from a population of a health district of the Barcelona province that has been exposed to asbestos for a period of 90 years.

DISCUSSION: A better understanding of asbestos-related diseases should improve i) the clinical and epidemiological follow up of patients with this condition; ii) the design of new treatment strategies; iii) and the development of preventive activities. At the end of the study, the two cohorts created in this study (affected cases and healthy controls) will constitute the basis for future research.}, } @article {pmid23907860, year = {2013}, author = {Diandini, R and Takahashi, K and Park, EK and Jiang, Y and Movahed, M and Le, GV and Lee, LJ and Delgermaa, V and Kim, R}, title = {Potential years of life lost (PYLL) caused by asbestos-related diseases in the world.}, journal = {American journal of industrial medicine}, volume = {56}, number = {9}, pages = {993-1000}, doi = {10.1002/ajim.22206}, pmid = {23907860}, issn = {1097-0274}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestosis/*mortality ; *Cost of Illness ; Databases, Factual ; Female ; Global Health/*statistics & numerical data ; Humans ; *Life Tables ; Male ; Mesothelioma/*mortality ; Middle Aged ; }, abstract = {BACKGROUND: We applied the well-established, but rather under-utilized, indicator of Potential Years of Life Lost (PYLL) to estimate the global burden of mesothelioma and asbestosis.

METHODS: We analyzed all deaths caused by mesothelioma and asbestosis that were reported by 82 and 55 countries, respectively, to the World Health Organization (WHO) from 1994 to 2010.

RESULTS: The 128,015 and 13,885 persons who died of mesothelioma and asbestosis, potentially lost a total of 2.18 million and 180,000 years of life (PYLL), or, an annual average PYLL of 201,000 years and 17,000 years, respectively. The average PYLL per decedent were 17.0 and 13.0 years for mesothelioma and asbestosis, respectively.

CONCLUSIONS: The current burden of asbestos-related diseases (ARDs) in terms of PYLL is substantial. The future burden of ARDs can be eliminated by stopping the use of asbestos.}, } @article {pmid23905972, year = {2013}, author = {Barlow, CA and Lievense, L and Gross, S and Ronk, CJ and Paustenbach, DJ}, title = {The role of genotoxicity in asbestos-induced mesothelioma: an explanation for the differences in carcinogenic potential among fiber types.}, journal = {Inhalation toxicology}, volume = {25}, number = {9}, pages = {553-567}, doi = {10.3109/08958378.2013.807321}, pmid = {23905972}, issn = {1091-7691}, mesh = {Animals ; Asbestos/*toxicity ; Carcinogens/*toxicity ; Humans ; Lung Neoplasms/*chemically induced ; Mesothelioma/*chemically induced ; Mutagens/*toxicity ; }, abstract = {The mechanism(s) underlying asbestos toxicity associated with the pathogenesis of mesothelioma has been a challenge to unravel for more than 60 years. A significant amount of research has focused on the characteristics of different fiber types and their potential to induce mesothelioma. These mechanistic studies of fiber toxicity have proceeded along two lines: those demonstrating biochemical mechanisms by which fibers induce disease and those investigating human susceptibility. Most recent studies focused on in vitro genotoxic effects induced by asbestos as the mechanism responsible for asbestos-induced disease. Although asbestos exerts a genotoxic effect at certain concentrations in vitro, a positive response in these tests does not indicate that the chemical is likely to produce an increased risk of carcinogenesis in exposed human populations. Thus far, findings from studies on the effects of fiber type in mesothelial cells are seriously flawed by a lack of a dose response relationship. The common limitation of these in vitro experiments is the lack of attention paid to the complexities of the human anatomy, biochemistry and physiology, which make the observed effects in these experimental systems difficult to extrapolate to persons in the workplace. Mechanistic differences between carcinogenic and genotoxic processes indicate why tests for genotoxicity do not provide much insight regarding the ability to predict carcinogenic potential in workers exposed to asbestos doses in the post-Occupational Safety and Health Administration era. This review discusses the existing literature on asbestos-induced genotoxicity and explains why these studies may or may not likely help characterize the dose-response curve at low dose.}, } @article {pmid23899865, year = {2013}, author = {Donaldson, K and Poland, CA and Murphy, FA and MacFarlane, M and Chernova, T and Schinwald, A}, title = {Pulmonary toxicity of carbon nanotubes and asbestos - similarities and differences.}, journal = {Advanced drug delivery reviews}, volume = {65}, number = {15}, pages = {2078-2086}, doi = {10.1016/j.addr.2013.07.014}, pmid = {23899865}, issn = {1872-8294}, support = {G0901697/MRC_/Medical Research Council/United Kingdom ; MC_U132685863/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; Asbestos/*toxicity ; Environmental Exposure/adverse effects ; Humans ; Inflammation/chemically induced/pathology ; Inhalation Exposure/adverse effects ; Lung/drug effects/pathology ; Lung Diseases/*chemically induced/pathology ; Nanotubes, Carbon/*toxicity ; Oxidative Stress/drug effects ; Pleural Diseases/chemically induced/pathology ; }, abstract = {Carbon nanotubes are a valuable industrial product but there is potential for human pulmonary exposure during production and their fibrous shape raises the possibility that they may have effects like asbestos, which caused a worldwide pandemic of disease in the20th century that continues into present. CNT may exist as fibres or as more compact particles and the asbestos-type hazard only pertains to the fibrous forms of CNT. Exposure to asbestos causes asbestosis, bronchogenic carcinoma, mesothelioma, pleural fibrosis and pleural plaques indicating that both the lungs and the pleura are targets. The fibre pathogenicity paradigm was developed in the 1970s-80s and has a robust structure/toxicity relationship that enables the prediction of the pathogenicity of fibres depending on their length, thickness and biopersistence. Fibres that are sufficiently long and biopersistent and that deposit in the lungs can cause oxidative stress and inflammation. They may also translocate to the pleura where they can be retained depending on their length, and where they cause inflammation and oxidative stress in the pleural tissues. These pathobiological processes culminate in pathologic change - fibroplasia and neoplasia in the lungs and the pleura. There may also be direct genotoxic effects of fibres on epithelial cells and mesothelium, contributing to neoplasia. CNT show some of the properties of asbestos and other types of fibre in producing these types of effects and more research is needed. In terms of the molecular pathways involved in the interaction of long biopersistent fibres with target tissue the events leading to mesothelioma have been a particular area of interest. A variety of kinase pathways important in proliferation are activated by asbestos leading to pre-malignant states and investigations are under way to determine whether fibrous CNT also affects these molecular pathways. Current research suggests that fibrous CNT can elicit effects similar to asbestos but more research is needed to determine whether they, or other nanofibres, can cause fibrosis and cancer in the long term.}, } @article {pmid23899648, year = {2014}, author = {Budroni, M and Cossu, A and Paliogiannis, P and Palmieri, G and Attene, F and Cesaraccio, R and Tanda, F}, title = {Epidemiology of malignant pleural mesothelioma in the province of Sassari (Sardinia, Italy). A population-based report.}, journal = {Annali italiani di chirurgia}, volume = {85}, number = {3}, pages = {244-248}, pmid = {23899648}, issn = {2239-253X}, mesh = {Adolescent ; Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; *Carcinogens ; Child ; Child, Preschool ; Female ; Humans ; Incidence ; Infant ; Infant, Newborn ; Italy/epidemiology ; Lung Neoplasms/*epidemiology/*etiology/mortality ; Male ; Mesothelioma/*epidemiology/*etiology/mortality ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/*epidemiology/*etiology/mortality ; Registries ; Retrospective Studies ; Risk Factors ; Sex Distribution ; Survival Rate ; }, abstract = {UNLABELLED: The aim of this population-based study was to analyze and describe the epidemiological characteristics and trends of malignant pleural mesothelioma in the province of Sassari (Sardinia, Italy), in the period 1992-2010. Data were obtained from the local tumor registry which makes part of a wider registry web, coordinated today by the Italian Association for Tumor Registries. The overall number of malignant pleural mesothelioma cases registered was 70. The male-to-female ratio was 4:1 and the mean age 65.1 years for males and 63.4 years for females. The standardized incidence rates were 1.2/100,000 and 0.3/100,000 and the standardized mortality rates 0.6/100,000 and 0.2/100,000 for males and females respectively. A trend to increase in incidence in recent years was evidenced. This trend seems to follow the general national tendency and it depends on a large diffusion of asbestos usage in the past, delayed legislative interventions and probably a cleaning strategy of residual contamination fonts to intensify. The relative 5 years survival was low, suggesting the necessity to further intensify research and cure methods for the treatment of this extremely aggressive disease.

KEY WORDS: Asbestos exposure, Mesothelioma, Pleura, Sassari.}, } @article {pmid23896078, year = {2013}, author = {Meisenkothen, C}, title = {Malignant mesothelioma, airborne asbestos, and the need for accuracy in chrysotile risk assessments.}, journal = {New solutions : a journal of environmental and occupational health policy : NS}, volume = {23}, number = {2}, pages = {389-405}, doi = {10.2190/NS.23.2.k}, pmid = {23896078}, issn = {1541-3772}, mesh = {Air Pollutants, Occupational/*toxicity ; Asbestos, Serpentine/*toxicity ; Connecticut ; Humans ; Lung Neoplasms/*etiology ; Male ; *Manufactured Materials ; Mesothelioma/*etiology ; Occupational Exposure/*adverse effects/legislation & jurisprudence ; Public Health ; *Risk Assessment ; }, abstract = {A man diagnosed with pleural mesothelioma sought legal representation with the author's law firm. He worked 33 years in a wire and cable factory in the northeastern United States (Connecticut) that exclusively used chrysotile asbestos in its manufacturing process. This is the first report of mesothelioma arising from employees of this factory. This report provides additional support for the proposition that chrysotile asbestos can cause malignant mesothelioma in humans. If chrysotile risk assessments are to be accurate, then the literature should contain an accurate accounting of all mesotheliomas alleged to be caused by chrysotile asbestos. This is important not just for public health professionals but also for individuals and companies involved in litigation over asbestos-related diseases. If reports such as these remain unknown, it is probable that cases of mesothelioma among chrysotile-exposed cohorts would go unrecognized and chrysotile-using factories would be incorrectly cited as having no mesotheliomas among their employees.}, } @article {pmid23887168, year = {2013}, author = {Goparaju, C and Donington, JS and Hsu, T and Harrington, R and Hirsch, N and Pass, HI}, title = {Overexpression of EPH receptor B2 in malignant mesothelioma correlates with oncogenic behavior.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {8}, number = {9}, pages = {1203-1211}, doi = {10.1097/JTO.0b013e31829ceb6a}, pmid = {23887168}, issn = {1556-1380}, mesh = {*Apoptosis ; Blotting, Western ; Case-Control Studies ; Cell Movement ; *Cell Proliferation ; Cells, Cultured ; Epithelium/metabolism/*pathology ; Fluorescent Antibody Technique ; Humans ; Immunoenzyme Techniques ; Lung Neoplasms/genetics/metabolism/*pathology ; Mesothelioma/genetics/metabolism/*pathology ; Mesothelioma, Malignant ; Peritoneum/metabolism/*pathology ; Prognosis ; RNA, Messenger/genetics ; RNA, Small Interfering/genetics ; Real-Time Polymerase Chain Reaction ; Receptor, EphB2/antagonists & inhibitors/genetics/*metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MM) is an aggressive asbestos-associated malignancy with limited therapeutic options. This study describes the overexpression of Ephrin B2 receptor (EPHB2) in MM cell lines and tumors, and the effect of its manipulation on proliferative and invasive qualities of the disease.

METHODS: Using expression arrays, we investigated EPHB2 in MM tumors compared with normal mesothelium. EPHB2 and downstream target expression were evaluated using reverse-transcriptase polymerase chain reaction and immunoblotting methods. The biological significance of EPHB2 in MM was evaluated using in vitro functional assays with and without targeting by EPHB2-short hairpin RNA or blocking peptide in two mesothelioma cell lines, HP-1 and H2595.

RESULTS: EPHB2 is overexpressed in all MM cell lines, but not in benign mesothelial cells, and is significantly elevated in MM tumor tissue compared with matched normal peritoneum. Targeted knockdown of EPHB2 in HP-1 and H2595 cell lines reduced its expression and that of EPHB2 downstream targets such as matrix metalloproteinase (MMP-2) and vascular endothelial growth factor, whereas caspase 2 and caspase 8 had increased expression. Inhibition of EPHB2 resulted in a significant decrease in scratch closure (1.25-fold-1.8-fold), proliferation (1.5-fold), and invasion (1.7-fold-1.8-fold) compared with the controls. Most notably, however, EPHB2 silencing resulted in a significant increase in apoptotic proteins and activity.

CONCLUSION: EPHB2 seems to play an important role in MM pathogenesis and these findings indicate that EPHB2 could serve as a potential novel therapeutic target for treatment of the disease.}, } @article {pmid23886156, year = {2013}, author = {Kim, MC and Cui, FJ and Kim, Y}, title = {Hydrogen peroxide promotes epithelial to mesenchymal transition and stemness in human malignant mesothelioma cells.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {14}, number = {6}, pages = {3625-3630}, doi = {10.7314/apjcp.2013.14.6.3625}, pmid = {23886156}, issn = {2476-762X}, mesh = {Apoptosis ; Blotting, Western ; Cadherins/genetics/metabolism ; Cell Adhesion ; Cell Movement ; Cell Proliferation ; Epithelial-Mesenchymal Transition/*drug effects ; Homeodomain Proteins/genetics/metabolism ; Humans ; Hydrogen Peroxide/*pharmacology ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics/metabolism ; Immunoenzyme Techniques ; Lung Neoplasms/drug therapy/metabolism/*pathology ; Mesothelioma/drug therapy/metabolism/*pathology ; Mesothelioma, Malignant ; Nanog Homeobox Protein ; Neoplastic Stem Cells/*drug effects/metabolism/pathology ; Octamer Transcription Factor-3/genetics/metabolism ; Oxidants/*pharmacology ; Oxidative Stress/drug effects ; RNA, Messenger/genetics ; Reactive Oxygen Species/*metabolism ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; SOXB1 Transcription Factors/genetics/metabolism ; Transforming Growth Factor beta1/genetics/metabolism ; Tumor Cells, Cultured ; Vimentin/genetics/metabolism ; }, abstract = {Reactive oxygen species (ROS) are known to promote mesothelial carcinogenesis that is closely associated with asbestos fibers and inflammation. Epithelial to mesenchymal cell transition (EMT) is an important process involved in the progression of tumors, providing cancer cells with aggressiveness. The present study was performed to determine if EMT is induced by H2O2 in human malignant mesothelioma (HMM) cells. Cultured HMM cells were treated with H2O2, followed by measuring expression levels of EMT-related genes and proteins. Immunohistochemically, TWIST1 expression was confined to sarcomatous cells in HMM tissues, but not in epithelioid cells. Treatment of HMM cells with H2O2 promoted EMT, as indicated by increased expression levels of vimentin, SLUG and TWIST1, and decreased E-cadherin expression. Expression of stemness genes such as OCT4, SOX2 and NANOG was also significantly increased by treatment of HMM cells with H2O2. Alteration of these genes was mediated via activation of hypoxia inducible factor 1 alpha (HIF-1α) and transforming growth factor beta 1 (TGF-β1). Considering that treatment with H2O2 results in excess ROS, the present study suggests that oxidative stress may play a critical role in HMM carcinogenesis by promoting EMT processes and enhancing the expression of stemness genes.}, } @article {pmid23885834, year = {2013}, author = {Kamp, DW and Liu, G and Cheresh, P and Kim, SJ and Mueller, A and Lam, AP and Trejo, H and Williams, D and Tulasiram, S and Baker, M and Ridge, K and Chandel, NS and Beri, R}, title = {Asbestos-induced alveolar epithelial cell apoptosis. The role of endoplasmic reticulum stress response.}, journal = {American journal of respiratory cell and molecular biology}, volume = {49}, number = {6}, pages = {892-901}, pmid = {23885834}, issn = {1535-4989}, support = {R01ES020357/ES/NIEHS NIH HHS/United States ; P01 HL071643/HL/NHLBI NIH HHS/United States ; P01HL071643/HL/NHLBI NIH HHS/United States ; R01 ES020357/ES/NIEHS NIH HHS/United States ; I01 BX000786/BX/BLRD VA/United States ; P30 HL101292/HL/NHLBI NIH HHS/United States ; }, mesh = {Alveolar Epithelial Cells/*drug effects/*pathology/physiology ; Animals ; Antioxidants/pharmacology ; Apoptosis/*drug effects/physiology ; Asbestos, Amosite/*toxicity ; Calcium Signaling/drug effects ; Cell Line ; Cells, Cultured ; DNA-Binding Proteins/genetics/metabolism ; Endoplasmic Reticulum Chaperone BiP ; Endoplasmic Reticulum Stress/*drug effects/physiology ; Endoribonucleases/genetics/metabolism ; Heat-Shock Proteins/genetics/metabolism ; Humans ; Membrane Proteins/genetics/metabolism ; Organometallic Compounds/pharmacology ; Phenylbutyrates/pharmacology ; Protein Serine-Threonine Kinases/genetics/metabolism ; RNA, Messenger/genetics/metabolism ; Rats ; Regulatory Factor X Transcription Factors ; Salicylates/pharmacology ; Thapsigargin/pharmacology ; Transcription Factor CHOP/genetics/metabolism ; Transcription Factors/genetics/metabolism ; bcl-X Protein/genetics/metabolism ; }, abstract = {Asbestos exposure results in pulmonary fibrosis (asbestosis) and malignancies (bronchogenic lung cancer and mesothelioma) by mechanisms that are not fully understood. Alveolar epithelial cell (AEC) apoptosis is important in the development of pulmonary fibrosis after exposure to an array of toxins, including asbestos. An endoplasmic reticulum (ER) stress response and mitochondria-regulated (intrinsic) apoptosis occur in AECs of patients with idiopathic pulmonary fibrosis, a disease with similarities to asbestosis. Asbestos induces AEC intrinsic apoptosis, but the role of the ER is unclear. The objective of this study was to determine whether asbestos causes an AEC ER stress response that promotes apoptosis. Using human A549 and rat primary isolated alveolar type II cells, amosite asbestos fibers increased AEC mRNA and protein expression of ER stress proteins involved in the unfolded protein response, such as inositol-requiring kinase (IRE) 1 and X-box-binding protein-1, as well as ER Ca[2](2+) release ,as assessed by a FURA-2 assay. Eukarion-134, a superoxide dismutase/catalase mimetic, as well as overexpression of Bcl-XL in A549 cells each attenuate asbestos-induced AEC ER stress (IRE-1 and X-box-binding protein-1 protein expression; ER Ca[2](2+) release) and apoptosis. Thapsigargin, a known ER stress inducer, augments AEC apoptosis, and eukarion-134 or Bcl-XL overexpression are protective. Finally, 4-phenylbutyric acid, a chemical chaperone that attenuates ER stress, blocks asbestos- and thapsigargin-induced AEC IRE-1 protein expression, but does not reduce ER Ca[2](2+) release or apoptosis. These results show that asbestos triggers an AEC ER stress response and subsequent intrinsic apoptosis that is mediated in part by ER Ca[2](2+) release.}, } @article {pmid23879063, year = {2013}, author = {Magnani, C and Fubini, B and Mirabelli, D and Bertazzi, PA and Bianchi, C and Chellini, E and Gennaro, V and Marinaccio, A and Menegozzo, M and Merler, E and Merletti, F and Musti, M and Pira, E and Romanelli, A and Terracini, B and Zona, A}, title = {Pleural mesothelioma: epidemiological and public health issues. Report from the Second Italian Consensus Conference on Pleural Mesothelioma.}, journal = {La Medicina del lavoro}, volume = {104}, number = {3}, pages = {191-202}, pmid = {23879063}, issn = {0025-7818}, mesh = {Humans ; Italy/epidemiology ; Mesothelioma/*epidemiology/etiology ; Pleural Neoplasms/*epidemiology/etiology ; *Public Health ; }, abstract = {Malignant mesothelioma is closely connected to asbestos exposure, with epidemiological patterns closely reshaping the geography and history of asbestos exposure. Mechanisms of causation and of interaction of asbestos fibres with pleura are complex and currently not yet completely understood. Curative efforts so far provided little results. Italy shows one of the highest incidence of MM and developed a network of specialized cancer registries in order to monitor disease occurrence and describe its epidemiology in details. The second Italian Consensus Conference on Pleural Mesothelioma convened in Torino on November 24th-25th, 2011. Besides the main consensus report summarizing the contribution of the different expertises, that was published elsewhere, the participants in 'Public Health and Epidemiology' section decided to report in major details the evidence and the conclusions regarding epidemiology, causative mechanisms and the public health impact of the disease.}, } @article {pmid23874067, year = {2013}, author = {Yamashita, K and Nagai, H and Kondo, Y and Misawa, N and Toyokuni, S}, title = {Evaluation of two distinct methods to quantify the uptake of crocidolite fibers by mesothelial cells.}, journal = {Journal of clinical biochemistry and nutrition}, volume = {53}, number = {1}, pages = {27-35}, pmid = {23874067}, issn = {0912-0009}, abstract = {Exposure to asbestos fibers increases the risk of mesothelioma in humans. One hypothetical carcinogenic mechanism is that asbestos fibers may directly induce mutations in mesothelial cells. Although the uptake of asbestos fibers by mesothelial cells is recognized, methods for the quantification of the uptake have not been well established. In the present study, we evaluated two distinct methods, using crocidolite fibers and MeT5A mesothelial cells. One method is histological evaluation using the cell-block technique, which allows for the direct cross-sectional observation of cells and fibers. We found the bright field observation with ×1000 magnification (oil-immersion) of the sample with Kernechtrot staining was most suitable for this purpose. The other method is flow cytometric analysis, which permits the evaluation of a much larger number of cells. We observed that the side scatter (SSC) increased with the intracellular fibers, and that the "mean SSC ratio (treated/control)" was useful for quantification. We could collect the cells with abundant internalized crocidolite fibers by sorting. Results of the two methodologies were correlated well in the experiments. The quantities of internalized fibers increased with incubation time and loaded dosage, but they were inversely associated with cellular density in culture.}, } @article {pmid23866375, year = {2013}, author = {Bahk, J and Choi, Y and Lim, S and Paek, D}, title = {Authors' reply. Why countries ban asbestos: the roots of political will.}, journal = {International journal of occupational and environmental health}, volume = {19}, number = {2}, pages = {137-138}, doi = {10.1179/1077352513Z.00000000061}, pmid = {23866375}, issn = {1077-3525}, mesh = {Air Pollutants/*toxicity ; Air Pollution, Indoor/*legislation & jurisprudence ; Asbestos/*toxicity ; Delivery of Health Care/*organization & administration ; Humans ; *International Cooperation ; Mesothelioma/*epidemiology ; *Policy ; }, } @article {pmid23863542, year = {2013}, author = {Carrillo, MC and Alturkistany, S and Roberts, H and Nguyen, E and Chung, TB and Paul, N and Herman, S and Weisbrod, G and Patsios, D}, title = {Low-dose computed tomography (LDCT) in workers previously exposed to asbestos: detection of parenchymal lung disease.}, journal = {Journal of computer assisted tomography}, volume = {37}, number = {4}, pages = {626-630}, doi = {10.1097/RCT.0b013e31828e1b8e}, pmid = {23863542}, issn = {1532-3145}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Asbestosis/*diagnostic imaging/epidemiology ; Comorbidity ; Environmental Exposure/*statistics & numerical data ; Environmental Monitoring/methods/*statistics & numerical data ; Female ; Humans ; Lung Neoplasms/*diagnostic imaging/epidemiology ; Male ; Mesothelioma/*diagnostic imaging/epidemiology ; Middle Aged ; Ontario/epidemiology ; Prevalence ; Radiation Dosage ; Reproducibility of Results ; Risk Factors ; Sensitivity and Specificity ; Smoking/epidemiology ; Tomography, X-Ray Computed/*methods/statistics & numerical data ; }, abstract = {OBJECTIVES: To evaluate the lungs of asymptomatic asbestos-exposed workers who were screened for lung cancer and mesothelioma using low-dose computed tomography (LDCT) for parenchymal abnormalities.

METHODS: Three hundred fifteen baseline LDCT studies of the chest of participants with at least 20 years' exposure to asbestos or presence of pleural plaques before enrollment on chest radiographs were analyzed.

RESULTS: Three hundred fifteen subjects were studied. The mean age was 61.7 years, and the mean exposure to asbestos was 26.9 years. One hundred seventy-five (56%) participants had absence of parenchymal findings with a mean age of 58.7 years, mean exposure of 24.6 years, and a mean smoking pack years of 19. One hundred forty subjects (44%) had parenchymal findings (138 men and 2 women) with a mean age of 65.3 years, mean exposure of 29.73 years, and a mean smoking pack years of 21.5 years. Participants who had parenchymal manifestations were more likely to be older and have longer exposure to asbestos compared to participants who had no relevant parenchymal findings. There was no statistical difference in the mean smoking pack years between the groups with and without parenchymal findings.

CONCLUSIONS: Low-dose CT could demonstrate parenchymal lung manifestations in this higher-risk asymptomatic group with prior exposure to asbestos in the setting of screening for lung cancer and mesothelioma. Individuals with longer exposure to asbestos and of higher age have more pulmonary abnormalities. The age and the latency of exposure play an important role given that the asbestos-related parenchymal abnormalities on LDCT were more prevalent in the elderly participants and with longer periods of exposure.}, } @article {pmid23846589, year = {2013}, author = {Yao, S and Chen, HH and Harte, E and Ventura, GD and Petibois, C}, title = {The role of asbestos morphology on their cellular toxicity: an in vitro 3D Raman/Rayleigh imaging study.}, journal = {Analytical and bioanalytical chemistry}, volume = {405}, number = {27}, pages = {8701-8707}, doi = {10.1007/s00216-013-7143-3}, pmid = {23846589}, issn = {1618-2650}, abstract = {Amphiboles caused cohorts of deaths in exposed workers, leading to some of the largest class actions in the industry. Once inhaled, these inorganic fibers are thought to be both chemically and morphologically toxic, and their biopersistence in the lungs over decades lead to progressive pathologies, mesothelioma, and asbestosis. However, this exceptionally long chronicity for human pathologies suggests that chemical toxicity is certainly low, suggesting that morphological parameters could be more relevant in the pathology. Here, we developed a 3D Raman/optical imaging methodology in vitro to characterize both morphological and chemical parameters of cell/fiber interactions. We determined that lung cells could vesiculate amphiboles with length below 5 μm or could embed those not exceeding 15 μm in their fibrous extracellular matrix. Lung cells can thus develop defense strategies for handling the biopersistence of inorganic species, which may thus have major impact for biosafety issues related to nanomaterials.}, } @article {pmid23846294, year = {2013}, author = {Lee, M and Alexander, HR and Burke, A}, title = {Diffuse mesothelioma of the peritoneum: a pathological study of 64 tumours treated with cytoreductive therapy.}, journal = {Pathology}, volume = {45}, number = {5}, pages = {464-473}, doi = {10.1097/PAT.0b013e3283631cce}, pmid = {23846294}, issn = {1465-3931}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Cell Proliferation ; Combined Modality Therapy ; Drug Therapy/*methods ; Female ; Humans ; Hyperthermia, Induced/*methods ; Lung Neoplasms/metabolism/*pathology/*therapy ; Male ; Mesothelioma/metabolism/*pathology/*therapy ; Mesothelioma, Malignant ; Middle Aged ; Neoplasm Invasiveness/pathology ; PAX8 Transcription Factor ; Paired Box Transcription Factors/metabolism ; Peritoneal Neoplasms/metabolism/*pathology/*therapy ; Peritoneum/metabolism/pathology/*surgery ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Diffuse peritoneal mesothelioma (DPM) forms a spectrum of indolent surface tumours to malignant invasive cancers. There are few pathological series that span well and poorly differentiated lesions that show diffuse peritoneal spread.

METHODS: Sixty-four DPM treated by initial cytoreductive therapy were retrospectively reviewed. Tumours were classified by surface and invasive growth pattern and correlated with risk factors, peritoneal cancer index (PCI) and completeness of cytoreduction (CCR). Degree of invasion was quantitated as absent (0), into stroma (I), into fat (II), and into adjacent structures (III) and was correlated with cytological features. Selected immunohistochemical stains were performed.

RESULTS: There were three well differentiated papillary mesotheliomas (WDPM; type A), four multicystic mesothelioma (type B), 22 tubulopapillary epithelioid mesotheliomas (type C), and 35 poorly differentiated epithelioid mesotheliomas with solid or sarcomatoid growth (Type D). Seven type D tumours had prominent sarcomatoid areas, 12 deciduoid areas, and four lymphohistiocytoid features. Risk factors were present in all groups except type A, and included prior abdominal surgery (n=24), asbestos exposure (n=5) and radiation (n=2). Extra-pleural mesothelioma was present in all groups except type B (total n=7, 11%). Two type A and eight type C tumours lacked invasion; only type D showed level III invasion. The invasive portion of one type A tumour and two type B tumours showed adenomatoid features. PCI and CCR were greater in type D compared to the other groups (p=0.02), as well as mitotic rate, degree of necrosis, and nuclear pleomorphism (p<0.001). Degree of invasion was strongly correlated with CCR (p=0.007), necrosis (p<0.0001), nuclear grade (p<0.0001), and mitotic rate (p=0.001), but not PCI (p=0.1). Immunohistochemical results were similar across groups, with frequent positivity for CA125 (94%), EGFR (94%) and calretinin (93%), followed by p16 (85%), cytokeratin 5,6 (76%), D2-40 (71%) and WT-1 (47%). PAX-8 was negative in all tumours, except one type A tumour that showed diffuse nuclear positivity.

CONCLUSIONS: Diffuse peritoneal mesotheliomas can be classified into four groups that reflect invasive potential, degree of adverse histological features, and amenability for CCR. Non-invasive tumours include both type A and type C tumours.}, } @article {pmid23841030, year = {2013}, author = {Pillai, K and Pourgholami, MH and Chua, TC and Morris, DL}, title = {Does the expression of BCL2 have prognostic significance in malignant peritoneal mesothelioma?.}, journal = {American journal of cancer research}, volume = {3}, number = {3}, pages = {312-322}, pmid = {23841030}, issn = {2156-6976}, abstract = {UNLABELLED: Background Malignant peritoneal mesothelioma (MPM) is a rare neoplasm of the peritoneal membrane that is causally related to asbestos exposure. Survival after treatment is poor. Current therapy involving hyperthermic intraperitoneal chemotherapy has improved survival in selective patients. In the past, several prognostic factors have been identified in MPM patients and this has prompted the development of new therapies and patient management. Since BCL2, an antiapoptotic oncoprotein, is a favourable prognostic factor in breast cancer, we investigated to determine the significance of BCL2 in MPM. Materials and Methods Forty two archival patient tumour sections embedded in paraffin blocks were sectioned and subjected to immunohistochemistry to detect BCL2. The staining intensity and abundance was classified using standard procedures and classified into two groups (0-4 = low & 5-8 = high expression). The distribution of BCL2 groups was examined in the different clinicopathological categories to determine prognosis using Kaplan-Meier survival analysis.

RESULTS: Univariate analysis revealed that in almost all clinicopathological categories, high BCL2 expression predisposed patients to a favourable prognosis. Independent of BCL2 expression, univariate analysis also showed that male gender, sarcomatoid histology, high PCI and age at diagnosis ≥ 60 years were associated poor prognosis. Multivariate analysis indicated that for all tumours, males and females, high BCL2 expression was associated with good prognosis. Further, independent of BCL2, age ≥ 60 years is an unfavourable prognostic factor.

CONCLUSION: Expression of BCL2 may serve to distinguish prognosis within the individual clinicopathological categories. BCL2 is also an independent variable in all tumours, males and females, with high expression being associated with good prognosis.}, } @article {pmid23837546, year = {2013}, author = {Berman, DW and Cox, LA and Popken, DA}, title = {Resisting the urge to act on random patterns: a reply to Schenker et al.}, journal = {Critical reviews in toxicology}, volume = {43}, number = {7}, pages = {609-610}, doi = {10.3109/10408444.2013.813439}, pmid = {23837546}, issn = {1547-6898}, mesh = {Asbestos/*analysis/toxicity ; Causality ; Health Policy ; Humans ; Logistic Models ; Mesothelioma/*chemically induced ; Public Health ; Regression Analysis ; }, } @article {pmid23828611, year = {2013}, author = {Mohammad-Taheri, Z and Nadji, SA and Raisi, F and Mohammadi, F and Bahadori, M and Mark, EJ}, title = {No association between simian virus 40 and diffuse malignant mesothelioma of the pleura in Iranian patients: a molecular and epidemiologic case-control study of 60 patients.}, journal = {American journal of industrial medicine}, volume = {56}, number = {10}, pages = {1221-1225}, doi = {10.1002/ajim.22160}, pmid = {23828611}, issn = {1097-0274}, mesh = {Adult ; Aged ; Aged, 80 and over ; Case-Control Studies ; Female ; Humans ; Iran/epidemiology ; Male ; Mesothelioma/epidemiology/*virology ; Middle Aged ; Pleural Neoplasms/epidemiology/*virology ; Polymerase Chain Reaction ; Polyomavirus Infections/epidemiology/*virology ; Simian virus 40/genetics ; Tumor Virus Infections/epidemiology/*virology ; }, abstract = {BACKGROUND: Diffuse malignant mesothelioma (DMM) is increasing in incidence on a worldwide basis and is linked to exposure to asbestos. Simian virus 40 (SV40), a DNA virus, was introduced inadvertently to human populations through contaminated polio vaccine during the years 1956-1963. It has been associated with various types of malignancy in animal experiments. There have been suggestions that SV40 might play a role in the pathogenesis of DMM.

OBJECTIVE: To evaluate the association between SV40 and DMM in Iranian patients.

METHOD: In a case-control study between the years 2007-2008, isolated DNA from 60 paraffin blocks of patients with DMM and 60 controls was assessed to detect three human polyomaviruses (JCV, BKV, and SV40) using three different sets of primers by multiplex nested PCR analysis. We related the patients with diffuse malignant mesothelioma to possible sites of exposure to asbestos.

RESULTS: None of the DMMs nor any patient in the control group had SV40 genome on polymerase chain reaction (PCR). All of the cases were SV40 T antigen negative.

CONCLUSION: This study suggests that DMM is independent of SV40 infection in Iran.}, } @article {pmid23827383, year = {2013}, author = {Cadby, G and Mukherjee, S and Musk, AW and Reid, A and Garlepp, M and Dick, I and Robinson, C and Hui, J and Fiorito, G and Guarrera, S and Beilby, J and Melton, PE and Moses, EK and Ugolini, D and Mirabelli, D and Bonassi, S and Magnani, C and Dianzani, I and Matullo, G and Robinson, B and Creaney, J and Palmer, LJ}, title = {A genome-wide association study for malignant mesothelioma risk.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {82}, number = {1}, pages = {1-8}, doi = {10.1016/j.lungcan.2013.04.018}, pmid = {23827383}, issn = {1872-8332}, mesh = {Aged ; Aged, 80 and over ; Case-Control Studies ; Cell Adhesion Molecules/*genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Immunoglobulins/*genetics ; Lung Neoplasms/*genetics ; Male ; Mesothelioma/*genetics ; Mesothelioma, Malignant ; Middle Aged ; *Polymorphism, Single Nucleotide ; Risk Factors ; ras Guanine Nucleotide Exchange Factors/*genetics ; }, abstract = {Malignant mesothelioma (MM) is a uniformly fatal tumour of mesothelial cells. MM is caused by exposure to asbestos however most individuals with documented asbestos exposure do not develop MM. Although MM appears to aggregate within families, the genetics of MM susceptibility is a relatively unexplored area. The aim of the current study was to identify genetic factors that contribute to MM risk. A genome-wide association analysis of 2,508,203 single nucleotide polymorphisms (SNPs) from 428 MM cases and 1269 controls from Western Australia was performed. Additional genotyping was performed on a sample of 778 asbestos-exposed Western Australian controls. Replication of the most strongly associated SNPs was undertaken in an independent case-control study of 392 asbestos-exposed cases and 367 asbestos-exposed controls from Italy. No SNPs achieved formal genome-wide statistical significance in the Western Australian study. However, suggestive results for MM risk were identified in the SDK1, CRTAM and RASGRF2 genes, and in the 2p12 chromosomal region. These findings were not replicated in the Italian study, although there was some evidence of replication in the region of SDK1. These suggestive associations will be further investigated in sequencing and functional studies.}, } @article {pmid23816056, year = {2013}, author = {Scherpereel, A and Grigoriu, BD and Noppen, M and Gey, T and Chahine, B and Baldacci, S and Trauet, J and Copin, MC and Dessaint, JP and Porte, H and Labalette, M}, title = {Defect in recruiting effector memory CD8+ T-cells in malignant pleural effusions compared to normal pleural fluid.}, journal = {BMC cancer}, volume = {13}, number = {}, pages = {324}, pmid = {23816056}, issn = {1471-2407}, mesh = {Aged ; CD4-Positive T-Lymphocytes/immunology/pathology ; CD8-Positive T-Lymphocytes/*immunology/pathology ; Exudates and Transudates/*immunology ; Female ; Flow Cytometry ; Humans ; Immunologic Memory/immunology ; Killer Cells, Natural/immunology/pathology ; Male ; Mesothelioma/*immunology/pathology ; Middle Aged ; Pleural Effusion/immunology/pathology ; Pleural Effusion, Malignant/*immunology/pathology ; Pleural Neoplasms/*immunology/pathology ; T-Lymphocyte Subsets/immunology/pathology ; }, abstract = {BACKGROUND: Malignant pleural effusions (MPE) are a common and fatal complication in cancers including lung or breast cancers, or malignant pleural mesothelioma (MPM). MPE animal models and immunotherapy trials in MPM patients previously suggested defects of the cellular immunity in MPE. However only few observational studies of the immune response were done in MPM patients, using questionable control groups (transudate…).

METHODS: We compared T cell populations evaluated by flow cytometry from blood and pleural effusion of untreated patients with MPM (n = 58), pleural metastasis of adenocarcinoma (n = 30) or with benign pleural lesions associated with asbestos exposure (n = 23). Blood and pleural fluid were also obtained from healthy subjects, providing normal values for T cell populations.

RESULTS: Blood CD4+ or CD8+ T cells percentages were similar in all groups of patients or healthy subjects. Whereas pleural fluid from healthy controls contained mainly CD8+ T cells, benign or malignant pleural effusions included mainly CD4+ T cells. Effector memory T cells were the main T cell subpopulation in pleural fluid from healthy subjects. In contrast, there was a striking and selective recruitment of central memory CD4+ T cells in MPE, but not of effector cells CD8+ T cells or NK cells in the pleural fluid as one would expect in order to obtain an efficient immune response.

CONCLUSIONS: Comparing for the first time MPE to pleural fluid from healthy subjects, we found a local defect in recruiting effector CD8+ T cells, which may be involved in the escape of tumor cells from immune response. Further studies are needed to characterize which subtypes of effector CD8+ T cells are involved, opening prospects for cell therapy in MPE and MPM.}, } @article {pmid23815672, year = {2013}, author = {Pinton, G and Manente, AG and Tavian, D and Moro, L and Mutti, L}, title = {Therapies currently in Phase II trials for malignant pleural mesothelioma.}, journal = {Expert opinion on investigational drugs}, volume = {22}, number = {10}, pages = {1255-1263}, doi = {10.1517/13543784.2013.816281}, pmid = {23815672}, issn = {1744-7658}, mesh = {Antineoplastic Agents/adverse effects/pharmacology/*therapeutic use ; Clinical Trials, Phase II as Topic ; Humans ; Immunotherapy/*methods ; Lung Neoplasms/blood supply/*drug therapy/immunology/metabolism ; Mesothelioma/blood supply/*drug therapy/immunology/metabolism ; Mesothelioma, Malignant ; Pleural Neoplasms/blood supply/*drug therapy/immunology/metabolism ; Treatment Outcome ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is an aggressive cancer associated with asbestos exposure, whose incidence will peak within the next years. Despite an overall low response rate, the current first-line therapy is represented by combined chemotherapy with cisplatin and antifolate. Moreover, there are no currently approved regimens for relapsed or refractory MPM. Therefore, it is clear how both preclinical and clinical researches aimed at identifying new therapeutic targets and testing them in early clinical settings are badly needed.

AREAS COVERED: The aim of this review is to summarize and critically comment the ongoing Phase II trials for MPM.

EXPERT OPINION: Over the past few years, there has been a significant endeavor of addressing the clinical research for MPM beyond the very modest results of chemotherapy. Nonetheless, our understanding is that the treatment of MPM should not be merely 'copied' from that of other much better studied tumors. In the light of recent results, studies toward the metabolic characteristics of this tumor are being progressively addressed. These evidences are disclosing a rather unusual model of malignancy, very likely to be more sensitive to novel 'MPM cells- and microenvironment-tailored' therapy addressing these characteristics rather than the sole cancer proliferation.}, } @article {pmid23807166, year = {2013}, author = {Lemen, RA and Frank, AL and Soskolne, CL and Weiss, SH and Castleman, B}, title = {Comment on 'estimating the asbestos-related lung cancer burden from mesothelioma mortality' - IARC and chrysotile risks.}, journal = {British journal of cancer}, volume = {109}, number = {3}, pages = {823-825}, pmid = {23807166}, issn = {1532-1827}, mesh = {Asbestos/*toxicity ; Carcinogens/*toxicity ; Humans ; Lung Neoplasms/*mortality ; Mesothelioma/*mortality ; }, } @article {pmid23807162, year = {2013}, author = {McCormack, V and Peto, J and Byrnes, G and Straif, K and Boffetta, P}, title = {Reply: comment on 'estimating the asbestos-related lung cancer burden from mesothelioma mortality'.}, journal = {British journal of cancer}, volume = {109}, number = {3}, pages = {825-826}, pmid = {23807162}, issn = {1532-1827}, mesh = {Asbestos/*toxicity ; Carcinogens/*toxicity ; Humans ; Lung Neoplasms/*mortality ; Mesothelioma/*mortality ; }, } @article {pmid23798235, year = {2013}, author = {Berra, A}, title = {[Letter to the Editors: Still on Asbestos. A Brief Review].}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {35}, number = {1}, pages = {61-62}, pmid = {23798235}, issn = {1592-7830}, mesh = {Asbestos/*adverse effects ; Asbestosis/complications/diagnosis/*epidemiology/etiology ; *Carcinogens ; European Union/statistics & numerical data ; Guidelines as Topic ; Humans ; Internet ; Italy/epidemiology ; Mesothelioma/diagnosis/*epidemiology/etiology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/diagnosis/*epidemiology/etiology ; }, } @article {pmid23796498, year = {2013}, author = {Vandenbos, F and Figueredo, M and Dumon-Gubeno, MC and Nicolle, I and Tarhini, A and Butori, C and Mouroux, J}, title = {[Malignant pleural mesothelioma after radiation treatment for Hodgkin lymphoma].}, journal = {Revue de pneumologie clinique}, volume = {69}, number = {5}, pages = {291-293}, doi = {10.1016/j.pneumo.2013.04.004}, pmid = {23796498}, issn = {1776-2561}, mesh = {Adult ; Hodgkin Disease/*radiotherapy ; Humans ; Lung Neoplasms/*diagnosis/etiology ; Male ; Mesothelioma/*diagnosis/etiology ; Mesothelioma, Malignant ; Neoplasms, Radiation-Induced/*diagnosis ; Pleural Neoplasms/*diagnosis/etiology ; Pleurisy/etiology ; Radiography, Thoracic ; }, abstract = {Malignant mesothelioma is a relatively uncommon malignancy. Although the pathogenesis is primarily related to asbestos, the role of ionizing radiation is more controversial. We report the case of a 41-year-old male who developed pleural mesothelioma. He had both, a prior short asbestos exposure and a thoracic radiotherapy for Hodgkin's disease 26years before. The evidence for radiotherapy as cause for mesothelioma is expanding and the diagnosis of mesothelioma in patients who had previous irradiation should be kept in mind.}, } @article {pmid23790737, year = {2013}, author = {Fujimoto, N and Gemba, K and Asano, M and Fuchimoto, Y and Wada, S and Ono, K and Ozaki, S and Kishimoto, T}, title = {Hyaluronic acid in the pleural fluid of patients with malignant pleural mesothelioma.}, journal = {Respiratory investigation}, volume = {51}, number = {2}, pages = {92-97}, doi = {10.1016/j.resinv.2013.02.002}, pmid = {23790737}, issn = {2212-5353}, mesh = {Diagnosis, Differential ; Female ; Humans ; Hyaluronic Acid/*analysis ; Lung Neoplasms/diagnosis/*metabolism ; Mesothelioma/diagnosis/*metabolism ; Mesothelioma, Malignant ; Pleural Effusion/*metabolism ; Pleural Neoplasms/diagnosis/*metabolism ; Retrospective Studies ; Sensitivity and Specificity ; }, abstract = {BACKGROUND: We retrospectively analyzed hyaluronic acid (HA) concentrations in pleural fluid and evaluated its utility for the differential diagnosis of malignant pleural mesothelioma (MPM).

METHODS: Pleural fluid HA concentrations were measured in 334 patients, including 50, 48, 85, 18, 86, 6, and 41 patients with MPM, benign asbestos pleurisy (BAP), lung cancer (LC), other malignant conditions (OMCs), infectious pleuritis (IP), collagen disease (CD), and other conditions, respectively.

RESULTS: The median (range) HA concentrations in pleural fluid were 78,700 (7920-2,630,000)ng/ml in the MPM group, 35,950 (900-152,000)ng/ml in the BAP group, 19,500 (2270-120,000)ng/ml in the LC group, 14,200 (900-101,000)ng/ml in the OMC group, 23,000 (900-230,000)ng/ml in the IP group, 24,600 (9550-80,800)ng/ml in the CD group, and 8140 (900-67,800)ng/ml in the other diseases group. HA levels were significantly higher in the MPM group than in the other groups. Receiver operating characteristic (ROC) analysis revealed an area under the ROC curve value of 0.832 (95% confidence interval, 0.765-0.898) for the differential diagnosis of MPM. With a cutoff value of 100,000ng/ml, the sensitivity and specificity were 44.0 and 96.5%, respectively. In the MPM group, HA values were significantly higher for the epithelioid subtype than for the sarcomatous subtype (p=0.007), and higher in earlier stages (I and II) than in advanced stages (III and IV) (p=0.007).

CONCLUSIONS: A diagnosis of MPM should be strongly considered in patients with pleural fluid HA concentrations exceeding 100,000ng/ml.}, } @article {pmid23789518, year = {2013}, author = {Romeo, E and Ascoli, V and Ancona, L and Balestri, A and Scalzo, CC and Cavariani, F and Compagnucci, P and Gasperini, L and Mataloni, F and Forastiere, F}, title = {[Occupational exposure to asbestos and incidence of malignant mesothelioma in the Lazio region, years 2001-2009: results of the activities of the regional register].}, journal = {La Medicina del lavoro}, volume = {104}, number = {2}, pages = {115-125}, pmid = {23789518}, issn = {0025-7818}, mesh = {Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Construction Materials ; Environmental Exposure ; Female ; Humans ; Incidence ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology/etiology ; Metallurgy ; Middle Aged ; Military Personnel ; *Occupational Exposure ; Pericardium ; Peritoneal Neoplasms/*epidemiology/etiology ; Pleural Neoplasms/*epidemiology/etiology ; Registries ; Sex Distribution ; }, abstract = {BACKGROUND: The Lazio Regional Mesothelioma Registry records the incident cases of Malignant Mesothelioma (MM) in residents in the Region since 2001.

OBJECTIVES: Estimate the incidence of MM in the Lazio Region (2001-2009) and assess possible asbestos exposures.

METHODS: The MM cases, notified by hospitals, regional protection and workplace safety units, Italian Workers' Compensation Authority, other regions, or extracted from hospital information systems and the regional registry of causes of death, are included in the register after analysis of diagnostic procedures (CT scan, chest X-ray, pathology reports and patients' records). Possible asbestos exposure is investigated by standardized interview and thereafter defined by a panel of experts, according to RENAM guidelines. The incidence of MM of the pleura and peritoneum (per 100,000 inhabitants) for the period 2001-2009 is calculated.

RESULTS: The incidence of MM among Lazio residents in the period 2001-2009 (600 cases) was estimated to be 1.8 among men and 0.5 among women per 100,000 inhabitants. Information on exposures was collectedfor 54% of the cases (251 men and 78 women); 72% of men (n. 179) and 9% of women (n. 7) had been occupationally exposed to asbestos. The study found that the largest number of cases with occupational exposure was among workers in the construction industry. The number of cases with unknown exposure was very high.

CONCLUSIONS: The registry's work revealed the existence of asbestos exposure circumstances that were not sufficiently characterized,for which it is suggested that more detailed industrial hygiene investigations be performed, as well as measurement of asbestos bodies and/or fibres in lung tissue.}, } @article {pmid23794323, year = {2013}, author = {Finkelstein, M}, title = {Reply to letter by Nolan and colleagues--re: the carcinogenicity of New York state talc dusts in humans.}, journal = {American journal of industrial medicine}, volume = {56}, number = {9}, pages = {1119-1124}, doi = {10.1002/ajim.22208}, pmid = {23794323}, issn = {1097-0274}, mesh = {Asbestos/*toxicity ; Humans ; Male ; Mesothelioma/*epidemiology ; *Mining ; Occupational Diseases/*epidemiology ; Occupational Exposure/*adverse effects ; Talc/*toxicity ; }, } @article {pmid23792972, year = {2013}, author = {Hwang, J and Ramachandran, G and Raynor, PC and Alexander, BH and Mandel, JH}, title = {Comprehensive assessment of exposures to elongate mineral particles in the taconite mining industry.}, journal = {The Annals of occupational hygiene}, volume = {57}, number = {8}, pages = {966-978}, doi = {10.1093/annhyg/met026}, pmid = {23792972}, issn = {1475-3162}, mesh = {Air Pollutants, Occupational/*analysis ; Analysis of Variance ; Asbestos, Amphibole/analysis ; Humans ; Inhalation Exposure/analysis ; Iron/*adverse effects ; Lung Neoplasms/etiology ; Mesothelioma ; *Mining ; Minnesota/epidemiology ; Occupational Exposure/adverse effects/*analysis ; Reproducibility of Results ; Respiratory Tract Diseases ; Silicates/*adverse effects ; United States/epidemiology ; }, abstract = {Since the 1970s, concerns have been raised about elevated rates of mesothelioma in the vicinity of the taconite mines in the Mesabi Iron Range. However, insufficient quantitative exposure data have hampered investigations of the relationship between cumulative exposures to elongate mineral particles (EMP) in taconite dust and adverse health effects. Specifically, no research on exposure to taconite dust, which includes EMP, has been conducted since 1990. This article describes a comprehensive assessment of present-day exposures to total and amphibole EMP in the taconite mining industry. Similar exposure groups (SEGs) were established to assess present-day exposure levels and buttress the sparse historical data. Personal samples were collected to assess the present-day levels of worker exposures to EMP at six mines in the Mesabi Iron Range. The samples were analyzed using National Institute for Occupational Safety and Health (NIOSH) methods 7400 and 7402. For many SEGs in several mines, the exposure levels of total EMP were higher than the NIOSH Recommended Exposure Limit (REL). However, the total EMP classification includes not only the asbestiform EMP and their non-asbestiform mineral analogs but also other minerals because the NIOSH 7400 cannot differentiate between these. The concentrations of amphibole EMP were well controlled across all mines and were much lower than the concentrations of total EMP, indicating that amphibole EMP are not major components of taconite EMP. The levels are also well below the NIOSH REL of 0.1 EMP cc(-1). Two different approaches were used to evaluate the variability of exposure between SEGs, between workers, and within workers. The related constructs of contrast and homogeneity were calculated to characterize the SEGs. Contrast, which is a ratio of between-SEG variability to the sum of between-SEG and between-worker variability, provides an overall measure of whether there are distinctions between the SEGs. Homogeneity, which is the ratio of the within-worker variance component to the sum of the between-worker and within-worker variance components, provides an overall measure of how similar exposures are for workers within an SEG. Using these constructs, it was determined that the SEGs are formed well enough when grouped by mine for both total and amphibole EMP to be used for epidemiological analysis.}, } @article {pmid23790315, year = {2013}, author = {Vandermeers, F and Neelature Sriramareddy, S and Costa, C and Hubaux, R and Cosse, JP and Willems, L}, title = {The role of epigenetics in malignant pleural mesothelioma.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {81}, number = {3}, pages = {311-318}, doi = {10.1016/j.lungcan.2013.05.014}, pmid = {23790315}, issn = {1872-8332}, mesh = {Antineoplastic Agents/pharmacology/therapeutic use ; Cell Transformation, Neoplastic/genetics ; Clinical Trials as Topic ; DNA (Cytosine-5-)-Methyltransferases/antagonists & inhibitors ; *Epigenesis, Genetic/drug effects ; Epigenomics ; Gene Expression Regulation, Neoplastic/drug effects ; Histone Deacetylase Inhibitors/pharmacology/therapeutic use ; Humans ; Lung Neoplasms/drug therapy/*genetics ; Mesothelioma/drug therapy/*genetics ; Mesothelioma, Malignant ; Pleural Neoplasms/*genetics ; }, abstract = {Malignant pleural mesothelioma (MPM) is an almost invariably fatal cancer of the pleura due to asbestos exposure. Increasing evidence indicates that unresponsiveness to chemotherapy is due to epigenetic errors leading to inadequate gene expression in tumor cells. The availability of compounds that modulate epigenetic modifications, such as histone acetylation or DNA methylation, offers new prospects for treatment of MPM. Here, we review latest findings on epigenetics in mesothelioma and present novel strategies for promising epigenetic therapies.}, } @article {pmid23788253, year = {2013}, author = {Roelofs, CR and Kernan, GJ and Davis, LK and Clapp, RW and Hunt, PR}, title = {Mesothelioma and employment in massachusetts: analysis of cancer registry data 1988-2003.}, journal = {American journal of industrial medicine}, volume = {56}, number = {9}, pages = {985-992}, doi = {10.1002/ajim.22218}, pmid = {23788253}, issn = {1097-0274}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Incidence ; Logistic Models ; Male ; Massachusetts/epidemiology ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Diseases/*epidemiology/etiology ; Odds Ratio ; Public Health Surveillance/*methods ; *Registries ; }, abstract = {BACKGROUND: Cancer registries can be used to monitor mesothelioma cases and to identify occupations and industries previously and newly associated with mesothelioma-causing asbestos exposure by using standard registry data on the "usual" occupation and industry of the case.

METHODS: We used the National Institute for Occupational Safety and Health's Standardized Occupational Industry Coding Software to code 564 mesothelioma cases for occupation and 543 for industry of the 1,424 incident mesothelioma in the Massachusetts Cancer Registry from 1988 to 2003. Additionally, we coded the occupation and industry of 80,184 comparison cancer cases (35% of comparison cases in our database). These were used to compute Standardized Morbidity Odds Ratios (SMORs).

RESULTS: Seventeen occupations and 11 industries had statistically significant elevated SMORs for mesothelioma. Occupations and industries historically associated with mesothelioma remained elevated in these results. However, we also found statistically significant elevated SMORs for several occupations and industries for which there was previously weak or no association such as chemical engineers, machine operators, and automobile mechanics and machine manufacturing, railroads, and the U.S. Postal Service.

CONCLUSIONS: Incident cases of mesothelioma do not appear to be declining in Massachusetts, as legacy exposures to asbestos continue to produce cases in individuals involved in shipbuilding and construction. Exposures in occupations and industries not previously associated with mesothelioma also contribute cases. Cancer registries, with improved data collection, should continue to be monitored for mesothelioma cases and asbestos exposures.}, } @article {pmid23787063, year = {2013}, author = {Nowak, AK and Brown, C and Millward, MJ and Creaney, J and Byrne, MJ and Hughes, B and Kremmidiotis, G and Bibby, DC and Leske, AF and Mitchell, PLR and Pavlakis, N and Boyer, M and Stockler, MR}, title = {A phase II clinical trial of the vascular disrupting agent BNC105P as second line chemotherapy for advanced Malignant Pleural Mesothelioma.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {81}, number = {3}, pages = {422-427}, doi = {10.1016/j.lungcan.2013.05.006}, pmid = {23787063}, issn = {1872-8332}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/*therapeutic use ; Benzofurans/administration & dosage/adverse effects/*therapeutic use ; Biomarkers/blood/metabolism ; Female ; GPI-Linked Proteins/blood/metabolism ; Humans ; Lung Neoplasms/diagnostic imaging/*drug therapy/mortality/*pathology ; Male ; Mesothelin ; Mesothelioma/diagnostic imaging/*drug therapy/mortality/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Neoplasm Staging ; Organophosphates/administration & dosage/adverse effects/*therapeutic use ; Pleural Neoplasms/diagnostic imaging/*drug therapy/mortality/*pathology ; Radiography ; Treatment Outcome ; Tubulin Modulators/administration & dosage/adverse effects/*therapeutic use ; Tumor Burden ; }, abstract = {BNC105P is a tubulin polymerisation inhibitor that selectively disrupts tumour vasculature and suppresses cancer cell proliferation. This agent has exhibited preclinical and phase I activity in Malignant Pleural Mesothelioma (MPM). This phase II, single arm trial investigated the efficacy and safety of BNC105P as second line therapy in MPM. Participants had progressive MPM after first line pemetrexed/platinum chemotherapy, ECOG PS 0-1, adequate organ function, and measurable disease. BNC105P 16 mg/m(2) was administered intravenously on day 1 and 8 every 21 days until progression or undue toxicity. The primary endpoint was centrally reviewed objective response rate (RR). Tumour response was assessed every two cycles using modified RECIST. 30 patients were enrolled in 10 months, predominantly male (90%), ECOG PS 1 (77%), epithelioid histology (67%), and non-metastatic disease (67%). All patients received at least one dose of study drug, with a median of 2 cycles. No significant haematologic, biochemical, or cardiac adverse events (AEs) were observed. Grade 3 or 4 AEs occurred in 10 patients (33%). There were 2 deaths on study: 1 cardiorespiratory, the other to pneumonia. We observed 1 partial response (3%); 13 patients had stable disease (43%). Median progression free survival was 1.5 months (95% CI 1.4-2.4); median overall survival was 8.2 months (95% CI 3.8-11.9). BNC105P was safe and tolerable. The sole response was insufficient to warrant further research as a single agent.}, } @article {pmid23780761, year = {2013}, author = {Hodgson, JT}, title = {Quality of evidence must guide risk assessment of asbestos, by Lenters, V; Burdorf, A; Vermeulen, R; Stayner, L; Heederik, D.}, journal = {The Annals of occupational hygiene}, volume = {57}, number = {5}, pages = {670-674}, doi = {10.1093/annhyg/met016}, pmid = {23780761}, issn = {1475-3162}, mesh = {*Asbestos ; Humans ; Mesothelioma/*chemically induced ; Research/*standards ; Risk Assessment/*standards ; }, } @article {pmid23780760, year = {2013}, author = {Berman, DW and Case, BW}, title = {Quality of evidence must guide risk assessment of asbestos, by Lenters, V; Burdorf, A; Vermeulen, R; Stayner, L; Heederik, D.}, journal = {The Annals of occupational hygiene}, volume = {57}, number = {5}, pages = {667-669}, doi = {10.1093/annhyg/met015}, pmid = {23780760}, issn = {1475-3162}, mesh = {*Asbestos ; Humans ; Mesothelioma/*chemically induced ; Research/*standards ; Risk Assessment/*standards ; }, } @article {pmid23777840, year = {2013}, author = {Muley, T and Dienemann, H and Herth, FJ and Thomas, M and Meister, M and Schneider, J}, title = {Combination of mesothelin and CEA significantly improves the differentiation between malignant pleural mesothelioma, benign asbestos disease, and lung cancer.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {8}, number = {7}, pages = {947-951}, doi = {10.1097/JTO.0b013e31828f696b}, pmid = {23777840}, issn = {1556-1380}, mesh = {Asbestosis/blood/*diagnosis ; Biomarkers, Tumor/blood ; Carcinoembryonic Antigen/*blood ; Carcinoma, Large Cell/blood/diagnosis ; Carcinoma, Squamous Cell/blood/diagnosis ; Diagnosis, Differential ; Female ; Follow-Up Studies ; GPI-Linked Proteins/*blood ; Humans ; Lung Neoplasms/blood/*diagnosis ; Male ; Mesothelin ; Mesothelioma/blood/*diagnosis ; Mesothelioma, Malignant ; Middle Aged ; Neoplasm Staging ; Pleural Neoplasms/blood/*diagnosis ; Prognosis ; ROC Curve ; Retrospective Studies ; Small Cell Lung Carcinoma/blood/*diagnosis ; }, abstract = {INTRODUCTION: Soluble mesothelin-related peptides (SMRP) have been reported as potential markers for the diagnosis of malignant pleural mesothelioma (MPM). We wondered, whether a combination with a carcinoembryonic antigen (CEA) test might improve the relatively low diagnostic yield of the SMRP test.

METHODS: In a retrospective study, SMRP (mesothelin) and CEA serum concentrations were measured, using commercially available kits, in 93 previously untreated MPM patients, 75 patients with benign asbestos disease, and 139 patients suffering from lung cancer (LC).

RESULTS: The differentiation between MPM, LC, and benign asbestos disease could be improved by applying the ratio mesothelin/CEA. Whereas CEA expression was found to be low in MPM, most LC patients had elevated CEA serum levels. The area under curve (AUC) of the receiver operator characteristics curve for mesothelin alone was found to be only 0.708. For mesothelin/CEA the AUC of the receiver operator characteristics curve increased to 0.978. The sensitivity was 93% (69%) at 95% (100%) specificity for the differentiation between MPM and LC. Comparison of MPM and benign asbestos disease showed that the AUC was 0.887 and the sensitivity 56% (47%) at 95% (100%) specificity. In contrast, the AUC for the mesothelin test alone was only 0.715, and for the CEA test alone it was 0.16. An average increment in sensitivity of 38% (range, 16%-63%) could be achieved by the quotient mesothelin/CEA compared with the sensitivity of mesothelin alone.

CONCLUSION: The diagnostic yield of the mesothelin test can be considerably improved when combined with a CEA test with regard to the differential diagnosis between MPM and LC and between MPM and benign asbestos disease.}, } @article {pmid23776320, year = {2012}, author = {Bianchi, C and Bianchi, T}, title = {Mesothelioma among shipyard workers in Monfalcone, Italy.}, journal = {Indian journal of occupational and environmental medicine}, volume = {16}, number = {3}, pages = {119-123}, pmid = {23776320}, issn = {0973-2284}, abstract = {BACKGROUND: The high mesothelioma incidence in Monfalcone, Italy, is mainly attributable to shipbuilding activity. Mesothelioma risk among shipyard workers in Monfalcone is poorly defined.

MATERIALS AND METHODS: Workers hired at the Monfalcone shipyards in the period 1950-1959 were identified by surveying shipyard roll. The list of the workers was coupled with the archive data of Monfalcone and Trieste Hospitals. Mesotheliomas diagnosed in the above people were reexamined.

RESULTS: Of 1,403 workers hired in 1950-1959, 35 were diagnosed with mesothelioma (34 pleural, one peritoneal) between 1978 and 2012. Latency periods exceeded 40 years in 31 cases. The highest percentage of mesotheliomas was observed among people aged 14-19 years at hiring time (3.4%). Four mesothelioma patients had a blood relative with the same tumor.

CONCLUSIONS: The present findings show high mesothelioma percentage among shipyard workers hired at young ages. The effects of asbestos exposure begun in 1950-1959 cannot be considered as exhausted.}, } @article {pmid23772303, year = {2013}, author = {Meng, X and Guzzo, TJ and Bing, Z}, title = {Malignant mesotheliomas in spermatic cords: reports of two cases and a brief review of literature.}, journal = {Rare tumors}, volume = {5}, number = {1}, pages = {e4}, pmid = {23772303}, issn = {2036-3605}, abstract = {Primary malignant mesothelioma (MM) of spermatic cord is extremely rare. We presented two malignant mesotheliomas involving the spermatic cords; one was primary, one secondary. The secondary one represented the direct involvement by a peritoneal MM. No occupational exposure to asbestos was identified in either patient. Both of them presented with a painless inguinal mass. Microscopically the primary MM was epithelioid type with tumor nests infiltrating adjacent adipose tissue, while the secondary MM grew in mixed type. No tumor necrosis was seen in the primary MM, while extensive necrosis was seen in the secondary one. Rare mitotic figure was seen in the primary MM while the mitosis in the secondary tumor was brisk, and with atypical mitosis. Immunohistochemically the tumor cells were positive for calretinin and CK5/6 and negative for BER-EP4 and BRST3 in both cases. The reported cases of primary MM from spermatic cord in English literature were briefly reviewed.}, } @article {pmid23760546, year = {2014}, author = {Datta, A and Smith, R and Fiorentino, F and Treasure, T}, title = {Surgery in the treatment of malignant pleural mesothelioma: recruitment into trials should be the default position.}, journal = {Thorax}, volume = {69}, number = {2}, pages = {194-197}, pmid = {23760546}, issn = {1468-3296}, support = {//British Heart Foundation/United Kingdom ; }, mesh = {Aged ; England ; Humans ; Lung Neoplasms/*surgery ; Mesothelioma/*surgery ; Mesothelioma, Malignant ; *Patient Selection ; Pleural Neoplasms/*surgery ; Pneumonectomy/*methods ; Prognosis ; Randomized Controlled Trials as Topic ; Registries ; Survival Analysis ; Treatment Outcome ; }, abstract = {BACKGROUND: Europe is at the peak of an epidemic of malignant pleural mesothelioma and the burden of disease is likely to continue rising in the large areas of the world where asbestos remains unregulated. Patients with mesothelioma present with thoracic symptoms and radiological changes so respiratory physicians take a leading role in diagnosis and management. Belief that the modest survival times reported after radical surgery, whether alone or as part of multimodal therapy, are longer than they it would have been without surgery relies on data from highly selected, uncontrolled, retrospectively analysed case series. The only randomised study, the Mesothelioma and Radical Surgery (MARS) trial showed no benefit. A simple modelling study of registry patients, described here, shows that an impression of longer survival is eroded when patients who were never candidates for operation on grounds of histology, performance status and age are sequentially excluded from the model.

CONCLUSION: Whenever the question arises `Might an operation help me?' there are two responses that can and should be given. The first is that there is doubt about whether there is any survival or symptomatic benefit from surgery but we know that there is harm. The second is that there are on-going studies, including two randomised trials, which patients should be informed about. The authors suggest that the default position for clinicians should be to encourage recruitment into these trials.}, } @article {pmid23756640, year = {2013}, author = {Fisseler-Eckhoff, A}, title = {[Surgical aspects of malignant pleural mesothelioma: from the perspective of pathology].}, journal = {Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen}, volume = {84}, number = {6}, pages = {479-486}, pmid = {23756640}, issn = {1433-0385}, mesh = {Asbestosis/complications/mortality/pathology ; Cell Proliferation ; Combined Modality Therapy ; Diagnosis, Differential ; Germany ; Guideline Adherence ; Humans ; Mesothelioma/mortality/*pathology/*surgery ; Neoplasm Grading ; Neoplasm Staging ; Pleura/pathology/surgery ; Pleural Neoplasms/mortality/*pathology/*surgery ; Pneumonectomy/methods ; Prognosis ; Survival Rate ; Thoracic Surgery, Video-Assisted/methods ; }, abstract = {The increased use of asbestos in Germany in the mid 1970s led occupational physicians, pulmonologists, thoracic surgeons and pathologists to the expectation of an increasing incidence and mortality in patients with pleural mesothelioma up to 2020. Prerequisite for curative surgery is a pathological anatomical tumor diagnosis on the basis of a biopsy and accurate tumor staging. In order to achieve reproducible results in the assessment of malignant pleural diseases, the pathological anatomical diagnosis of malignant pleural mesothelioma should be made according to the guidelines of the international mesothelioma interest group (IMIG). Currently used multimodal thoracic surgery therapeutic concepts present new challenges and problems to the pathological anatomical diagnosis and are discussed in this article.}, } @article {pmid23751780, year = {2013}, author = {Toyokuni, S}, title = {Genotoxicity and carcinogenicity risk of carbon nanotubes.}, journal = {Advanced drug delivery reviews}, volume = {65}, number = {15}, pages = {2098-2110}, doi = {10.1016/j.addr.2013.05.011}, pmid = {23751780}, issn = {1872-8294}, mesh = {Animals ; Asbestos/toxicity ; Carcinogens/toxicity ; Humans ; Inhalation Exposure/adverse effects ; Mutagenicity Tests ; Nanotubes, Carbon/chemistry/*toxicity ; Neoplasms/etiology/pathology ; Occupational Diseases/etiology/*prevention & control ; Occupational Exposure/*adverse effects ; Particle Size ; Rats ; Risk Assessment ; }, abstract = {Novel materials are often commercialized without a complete assessment of the risks they pose to human health because such assessments are costly and time-consuming; additionally, sometimes the methodology needed for such an assessment does not exist. Carbon nanotubes have the potential for widespread application in engineering, materials science and medicine. However, due to the needle-like shape and high durability of multiwalled carbon nanotubes (MWCNTs), concerns have been raised that they may induce asbestos-like pathogenicity when inhaled. Indeed, experiments in rodents supported this hypothesis. Notably, the genetic alterations in MWCNT-induced rat malignant mesothelioma were similar to those induced by asbestos. Single-walled CNTs (SWCNTs) cause mitotic disturbances in cultured cells, but thus far, there has been no report that SWCNTs are carcinogenic. This review summarizes the recent noteworthy publications on the genotoxicity and carcinogenicity of CNTs and explains the possible molecular mechanisms responsible for this carcinogenicity. The nanoscale size and needle-like rigid structure of CNTs appear to be associated with their pathogenicity in mammalian cells, where carbon atoms are major components in the backbone of many biomolecules. Publishing adverse events associated with novel materials is critically important for alerting people exposed to such materials. CNTs still have a bright future with superb economic and medical merits. However, appropriate regulation of the production, distribution and secondary manufacturing processes is required, at least to protect the workers.}, } @article {pmid23749908, year = {2013}, author = {Kuramitsu, Y and Tominaga, W and Baron, B and Tokuda, K and Wang, Y and Kitagawa, T and Nakamura, K}, title = {Up-regulation of DDX39 in human malignant pleural mesothelioma cell lines compared to normal pleural mesothelial cells.}, journal = {Anticancer research}, volume = {33}, number = {6}, pages = {2557-2560}, pmid = {23749908}, issn = {1791-7530}, mesh = {Biomarkers, Tumor/metabolism ; Cell Line, Tumor ; DEAD-box RNA Helicases/*metabolism ; Humans ; Lung Neoplasms/*metabolism ; Mesothelioma/*metabolism ; Mesothelioma, Malignant ; Pleural Neoplasms/*metabolism ; Up-Regulation ; }, abstract = {Malignant pleural mesothelioma (MPM) is a malignant tumor originating from mesothelial cells existing in pleura. Since its incidence, it is closely related to the amount and time of exposure to asbestos, and the latency period after exposure to asbestos is very long, the incidence may increase over the next two decades. Since early detection is very difficult and there is no standard curative therapy, it is important to understand the biology of MPM, and to find biomarkers and molecular targets for its therapy. DDX39 is one of the Asp-Glu-Ala-Asp (DEAD)-box RNA helicases, which are required for the export of mRNA out of the nucleus, and transcription, splicing and transport of mRNA. Some reports have shown differential expression of DDX39 in tumor cells or tissues such as lung squamous cell cancer, gastrointestinal stromal tumor and urinary bladder cancer. In the present study, the protein levels of DDX39 in the human MPM cell lines NCI-H28, NCI-H2052 and NCI-H2452, and the human pleural mesothelial cell line MeT-5A were investigated by western blotting. The protein levels of DDX39 were found to be higher in NCI-H28, NCI-H2052 and NCI-H2452 compared to MeT-5A. The intensity of the bands of DDX39 in NCI-H28, NCI-H2052 and NCI-H2452 cells were increased by 1.351-, 1.887- and 2.024-fold, respectively, compared to MPM cells. These results suggest that DDX39 is a possible candidate biomarker for molecular-targeting of MPM.}, } @article {pmid23743993, year = {2013}, author = {Ried, M and Speth, U and Potzger, T and Neu, R and Diez, C and Klinkhammer-Schalke, M and Hofmann, HS}, title = {[Regional treatment of malignant pleural mesothelioma: results from the tumor centre Regensburg].}, journal = {Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen}, volume = {84}, number = {11}, pages = {987-993}, pmid = {23743993}, issn = {1433-0385}, mesh = {Age Factors ; Aged ; Aged, 80 and over ; Asbestosis/complications ; Biopsy ; *Cancer Care Facilities ; Cross-Sectional Studies ; Female ; Germany ; Humans ; Male ; Mesothelioma/epidemiology/mortality/pathology/*surgery ; Middle Aged ; Neoplasm Staging ; Palliative Care ; Pleura/pathology/surgery ; Pleural Neoplasms/epidemiology/mortality/pathology/*surgery ; Pleurodesis ; Population Dynamics ; Retrospective Studies ; Survival Rate ; Thoracoscopy ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is an aggressive, malignant tumor of the pleural surface and is strongly associated with asbestos exposure. Incidence of MPM will reach its peak over the coming years. Most patients present with advanced tumor stages and therefore surgical options are limited.

PATIENTS AND METHODS: Retrospective analysis of all patients with MPM reported to the tumor centre Regensburg between January 1998 and August 2011.

RESULTS: A total of 118 patients (85 % male) with cytologically or histologically confirmed MPM were reported. The mean age at diagnosis was 67 years (range 45-84 years) and 65 % of patients had a history of asbestos exposure. The incidence of MPM at the tumor centre Regensburg was 0.8/100,000 inhabitants with obvious regional differences depending on asbestos exposure. Staging was completed in 81 patients (67 %): stage I 9 %, stage II 22 %, stage III 23 % and stage IV 46 %. Of the patients 87 (74 %) underwent at least one surgical procedure: diagnostic thoracoscopy with biopsy (n = 37, 43 %), debulking surgery or talcum pleurodesis (n = 33, 38 %) and potentially curative resection (n = 17, 19 %). After a mean follow-up of 20 months the overall median survival was 14 months (1 year survival rate 62 %, 3 year survival rate 15 %). Patients had a significantly better median survival of 18 months after curative resection.

CONCLUSIONS: The distribution of MPM varies according to regional and industrial asbestos exposure. Screening and diagnostics should concentrate on locations with higher incidence of MPM to facilitate surgical therapy in a multimodal treatment regime.}, } @article {pmid23743702, year = {2013}, author = {di Orio, F and Zazzara, F}, title = {[Asbestos and harmful health effects: from denial theories to epidemiological evidence].}, journal = {Igiene e sanita pubblica}, volume = {69}, number = {2}, pages = {229-238}, pmid = {23743702}, issn = {0019-1639}, mesh = {Asbestos/*adverse effects ; Asbestosis/*epidemiology/*etiology ; Humans ; Mesothelioma/chemically induced/epidemiology ; Pleural Neoplasms/chemically induced/epidemiology ; }, abstract = {The recent episode involving Eternit, a factory in Casale Monferrato (Turin, Italy), culminated in February 2012 with a guilty verdict for the owners of the factory. The indiscriminate use of asbestos, however, continues worldwide, despite evidence of increased risk for conditions such as asbestosis and malignant pleural mesothelioma. In this study we investigate the relationship between epidemiological evidence and denial theories, over the decades and until the present time. Many countries in the world still promote the use of asbestos, with a view to profit and globalization but at the expense of public health.}, } @article {pmid23732197, year = {2013}, author = {Zurbriggen, R and Capone, L}, title = {[Pulmonary disease due to asbestos in steel industry workers].}, journal = {Medicina}, volume = {73}, number = {3}, pages = {224-230}, pmid = {23732197}, issn = {0025-7680}, mesh = {Aged ; Aged, 80 and over ; Argentina/epidemiology ; Asbestos/*adverse effects ; Asbestosis/diagnostic imaging/*etiology/pathology ; Female ; Humans ; Lung Neoplasms/diagnostic imaging/pathology ; Male ; *Metallurgy ; Middle Aged ; Occupational Exposure/*adverse effects ; Pleural Diseases/diagnostic imaging/*etiology/pathology ; Pleural Neoplasms/diagnostic imaging/pathology ; Radiography ; Smoking/epidemiology ; Steel ; }, abstract = {Asbestos-related diseases are caused by the inhalation of asbestos fibers in their variety chrysotile or white asbestos. Although the ban in Argentina dates from 2003, there are numerous industries where work continues with this mineral, including iron and steel industries. It is currently known the high pathogenicity of this material, so that in many countries there are programs to monitoring the exposed workers. Here we describe the general characteristics and pulmonary manifestations in 27 patients who had worked in a very huge steel factory in South America. The diagnosis of asbestos-related diseases was made by a medical-occupational record, history of asbestos exposure, additional studies of lung function and chest images. Then the sources of exposure (occupational, domestic and environmental), exposure time and latency period were analyzed, in those patients in whom a related disease was detected. Smoking history was also taken into account. Twenty-two patients had benigns pathologies (81.4%), sixteen of them with lesions localyzed in pleura, and other six pulmonary asbestosis. The malignant pathologies occurred in five patients (18.5%), in four of them mesothelioma and in other one lung cancer. The problem of asbestos exposure has contemporary relevance. Hence the need for a surveillance program in workers exposed to asbestos in the past or currently, to detect, report, record and investigate the characteristics of these pathologies.}, } @article {pmid23729401, year = {2013}, author = {Nuvoli, B and Galati, R}, title = {Cyclooxygenase-2, epidermal growth factor receptor, and aromatase signaling in inflammation and mesothelioma.}, journal = {Molecular cancer therapeutics}, volume = {12}, number = {6}, pages = {844-852}, doi = {10.1158/1535-7163.MCT-12-1103}, pmid = {23729401}, issn = {1538-8514}, mesh = {Aromatase/*genetics/metabolism ; Asbestos/toxicity ; Cyclooxygenase 2/*genetics ; ErbB Receptors/*genetics/metabolism ; Humans ; Inflammation/genetics/*pathology ; Lung Neoplasms/chemically induced/*genetics/pathology/therapy ; Mesothelioma/chemically induced/*genetics/pathology/therapy ; Mesothelioma, Malignant ; Molecular Targeted Therapy ; Pleural Neoplasms/chemically induced/genetics/pathology/therapy ; Signal Transduction ; }, abstract = {Malignant mesothelioma or mesothelioma is a rare form of cancer that develops from transformed cells originating in the mesothelium, the protective lining that covers many of the internal organs of the body. It is directly linked to asbestos exposure, which acts as a carcinogen by initiating the carcinogenic process. Because of their shape, asbestos fibers can cross the membrane barriers inside the body and cause inflammatory and fibrotic reactions. Such reactions are believed to be the mechanism by which asbestos fibers may trigger malignant mesothelioma in the pleural membrane around the lungs. Carcinogens are known to modulate the transcription factors, antiapoptotic proteins, proapoptotic proteins, protein kinases, cell-cycle proteins, cell adhesion molecules, COX-2, and growth factor signaling pathways. This article reviews recent studies regarding some malignant mesothelioma molecular targets not only for cancer prevention but also for cancer therapy.}, } @article {pmid23721559, year = {2013}, author = {Liu, R and Ferguson, BD and Zhou, Y and Naga, K and Salgia, R and Gill, PS and Krasnoperov, V}, title = {EphB4 as a therapeutic target in mesothelioma.}, journal = {BMC cancer}, volume = {13}, number = {}, pages = {269}, pmid = {23721559}, issn = {1471-2407}, support = {1R43 CA 168158-01/CA/NCI NIH HHS/United States ; 1R43 CA 171538-01/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antibodies, Monoclonal, Humanized/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/*administration & dosage ; Bevacizumab ; Cell Line, Tumor ; Drug Delivery Systems ; Fluorescent Antibody Technique ; Humans ; Immunohistochemistry ; In Situ Nick-End Labeling ; Male ; Mesothelioma/*metabolism ; Mice ; Mice, Inbred BALB C ; Pleural Neoplasms/*metabolism ; Receptor, EphB4/administration & dosage/*metabolism ; Serum Albumin/administration & dosage ; Xenograft Model Antitumor Assays ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) often develops decades following exposure to asbestos. Current best therapy produces a response in only half of patients, and the median survival with this therapy remains under a year. A search for novel targets and therapeutics is underway, and recently identified targets include VEGF, Notch, and EphB4-Ephrin-B2. Each of these targets has dual activity, promoting tumor cell growth as well as tumor angiogenesis.

METHODS: We investigated EphB4 expression in 39 human mesothelioma tissues by immunohistochemistry. Xenograft tumors established with human mesothelioma cells were treated with an EphB4 inhibitor (monomeric soluble EphB4 fused to human serum albumin, or sEphB4-HSA). The combinatorial effect of sEphB4-HSA and biologic agent was also studied.

RESULTS: EphB4 was overexpressed in 72% of mesothelioma tissues evaluated, with 85% of epithelioid and 38% of sarcomatoid subtypes demonstrating overexpression. The EphB4 inhibitor sEphB4-HSA was highly active as a single agent to inhibit tumor growth, accompanied by tumor cell apoptosis and inhibition of PI3K and Src signaling. Combination of sEphB4-HSA and the anti-VEGF antibody (Bevacizumab) was superior to each agent alone and led to complete tumor regression.

CONCLUSION: EphB4 is a potential therapeutic target in mesothelioma. Clinical investigation of sEphB4-HSA as a single agent and in combination with VEGF inhibitors is warranted.}, } @article {pmid23720698, year = {2013}, author = {Neumann, V and Löseke, S and Nowak, D and Herth, FJ and Tannapfel, A}, title = {Malignant pleural mesothelioma: incidence, etiology, diagnosis, treatment, and occupational health.}, journal = {Deutsches Arzteblatt international}, volume = {110}, number = {18}, pages = {319-326}, pmid = {23720698}, issn = {1866-0452}, mesh = {Asbestosis/*diagnosis/mortality/*therapy ; Causality ; Comorbidity ; Evidence-Based Medicine ; Humans ; Mesothelioma/*diagnosis/mortality/*therapy ; Occupational Exposure/*statistics & numerical data ; Occupational Health/statistics & numerical data ; Pleural Effusion, Malignant/*diagnosis/mortality/*therapy ; Prevalence ; Prognosis ; Risk Assessment ; Risk Factors ; Survival Analysis ; Survival Rate ; Treatment Outcome ; }, abstract = {BACKGROUND: The incidence of malignant mesothelioma in Germany is about 20 cases per million persons per year. Its association with asbestos exposure, usually occupational, has been unequivocally demonstrated. Even though the industrial use of asbestos was forbidden many years ago, new cases of mesothelioma continue to appear because of the long latency of the disease (median, 50 years). Its diagnosis and treatment still present a major challenge for ambulatory and in-hospital care and will do so for years to come.

METHODS: This article is based on a selective review of the literature, along with data from the German Mesothelioma Register.

RESULTS: 1397 people died of mesothelioma in Germany in 2010. A plateau in the incidence of the disease is predicted between 2015 and 2030. Most mesotheliomas arise from the pleura. The histological subtype and the Karnofsky score are the main prognostic factors. Only limited data are now available to guide treatment with a combination of the available methods (chemotherapy, surgery, radiotherapy). The prognosis is still poor, with a median survival time of only 12 months. Symptom control and the preservation of the patient's quality of life are the main aspects of care for patients with mesothelioma.

CONCLUSION: The incidence of mesothelioma is not expected to drop in the next few years. The available treatments are chemotherapy, surgery, and radiotherapy. Specialized treatment centers now increasingly provide multimodal therapy for treatment of mesothelioma.}, } @article {pmid23714495, year = {2013}, author = {Kindler, HL}, title = {Peritoneal mesothelioma: the site of origin matters.}, journal = {American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting}, volume = {}, number = {}, pages = {182-188}, doi = {10.14694/EdBook_AM.2013.33.182}, pmid = {23714495}, issn = {1548-8756}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Asbestos/toxicity ; Cytoreduction Surgical Procedures ; Female ; Germ-Line Mutation ; Humans ; Hyperthermia, Induced ; Lung Neoplasms/*diagnosis/*etiology/mortality/*therapy ; Male ; Mesothelioma/*diagnosis/*etiology/mortality/*therapy ; Mesothelioma, Malignant ; Pemetrexed/therapeutic use ; Peritoneal Neoplasms/*diagnosis/*etiology/mortality/*therapy ; Pleural Neoplasms/etiology/therapy ; Survivors ; Tumor Suppressor Proteins/genetics ; Ubiquitin Thiolesterase/genetics ; United States ; }, abstract = {The etiology, gender distribution, pathology, natural history, and treatment options for mesothelioma (MM) differ substantially depending on the site of origin. Peritoneal mesothelioma (MPeM) is a rare disease, comprising only approximately 10% to 15% of the 2,500 cases of MM diagnosed in the United States each year. Patients with MPeM are younger than patients with pleural MM, and a higher proportion, mostly women, are long-term survivors. Most MPeM is caused by asbestos exposure. Germ-line mutations of BAP1 (BRCA associated protein 1) can predispose to MM, uveal melanoma, and potentially other cancers. MPeM can be challenging to diagnose, and cytology is rarely helpful. Review by an experienced pathologist using a panel of at least two positive and two negative immunohistochemical stains is essential. The three major pathologic subtypes are epithelial, sarcomatoid, and biphasic. Most cases are epithelial; the others have a dismal prognosis. Two indolent subtypes of borderline malignant potential-well-differentiated papillary mesothelioma and benign multicystic mesothelioma-are more common in the peritoneum and are treated surgically. In highly selected patients receiving treatment at experienced referral centers, an aggressive locoregional strategy that combines cytoreductive surgery to remove all gross disease and hyperthermic intraperitoneal chemotherapy to treat residual microscopic tumors yields a 3-year survival of 60% and a median survival approaching 5 years, far better than expected from historic controls. This approach also provides durable palliation of malignant ascites in nearly all patients. Pemetrexed is the only U.S. Food and Drug Administration (FDA)-approved systemic chemotherapy for pleural MM. Largely on the basis of data from pharmaceutical registry studies, the activity of pemetrexed-based chemotherapy appears to be similar in pleural MM and MPeM.}, } @article {pmid23711077, year = {2014}, author = {Prazakova, S and Thomas, PS and Sandrini, A and Yates, DH}, title = {Asbestos and the lung in the 21st century: an update.}, journal = {The clinical respiratory journal}, volume = {8}, number = {1}, pages = {1-10}, doi = {10.1111/crj.12028}, pmid = {23711077}, issn = {1752-699X}, mesh = {Asbestosis/complications/diagnosis ; Developing Countries ; Humans ; Lung Diseases/etiology ; Mesothelioma/etiology ; *Occupational Exposure/statistics & numerical data ; Pleura/pathology ; Pleural Effusion/etiology ; Positron-Emission Tomography ; Tomography, X-Ray Computed ; }, abstract = {The asbestos-related disorders (ARDs) are currently of significant occupational and public health concern. Asbestos usage has been banned in most developed countries, but asbestos is still used in many developing countries and the number of cases of ARDs worldwide is rising. Many countries are now experiencing an epidemic of ARDs that is the legacy of occupational exposure in the 1960s-1980s because of the long latency period between asbestos exposure and manifestation of disease. It is likely that asbestos-related mortality and morbidity will continue to increase. Although the most feared complications of asbestos inhalation are the malignant conditions such as mesothelioma and lung cancer, asbestos inhalation more frequently results in benign conditions such as pleural plaques, diffuse pleural thickening, and asbestosis (pulmonary fibrosis due to asbestos exposure). Over recent years, there have been changes in the epidemiology of mesothelioma, in clinical management of ARDs and developments in new techniques for early detection of malignancy. This review provides an update on the respiratory manifestations of asbestos exposure and also considers advances in screening methods that may affect future management in the workplace.}, } @article {pmid23702885, year = {2013}, author = {Farioli, A and Violante, FS and Mattioli, S and Curti, S and Kriebel, D}, title = {Risk of mesothelioma following external beam radiotherapy for prostate cancer: a cohort analysis of SEER database.}, journal = {Cancer causes & control : CCC}, volume = {24}, number = {8}, pages = {1535-1545}, pmid = {23702885}, issn = {1573-7225}, mesh = {Aged ; Aged, 80 and over ; Cohort Studies ; Follow-Up Studies ; Humans ; Incidence ; Male ; Mesothelioma/epidemiology/*etiology ; Neoplasms, Radiation-Induced/epidemiology/*etiology ; Neoplasms, Second Primary/epidemiology/*etiology ; Prognosis ; Prostatic Neoplasms/complications/*radiotherapy ; Radiotherapy/*adverse effects ; Risk Factors ; SEER Program ; United States/epidemiology ; }, abstract = {PURPOSE: To investigate the association between external beam radiotherapy (EBRT) for prostate cancer and mesothelioma using data from the US Surveillance, Epidemiology, and End Results (SEER) cancer registries.

METHODS: We analyzed data from the SEER database (1973-2009). We compared EBRT versus no radiotherapy. Incidence rate ratios (IRR) and 95 % confidence intervals (95 % CI) of mesothelioma among prostate cancer patients were estimated with multilevel Poisson models adjusted by race, age, and calendar year. Confounding by asbestos was investigated using relative risk of mesothelioma in each case's county of residence as a proxy for asbestos exposure.

RESULTS: Four hundred and seventy-one mesothelioma cases (93.6 % pleural) occurred in 3,985,991 person-years. The IRR of mesothelioma was increased for subjects exposed to EBRT (1.28; 95 % CI 1.05, 1.55) compared to non-irradiated patients, and a population attributable fraction of 0.49 % (95 % CI 0.11, 0.81) was estimated. The IRR increased with latency period: 0-4 years, IRR 1.08 (95 % CI 0.81, 1.44); 5-9 years, IRR 1.31 (95 % CI 0.93, 1.85); ≥10 years, IRR 1.59 (95 % CI 1.05, 2.42). Despite the fairly strong evidence of association with EBRT, the population attributable rate of mesothelioma was modest-3.3 cases per 100,000 person-years. The cumulative incidence of mesothelioma attributable to EBRT was 4.0/100,000 over 5 years, 24.5/100,000 over 10 years, and 65.0/100,000 over 15 years.

CONCLUSIONS: Our study provides evidence that EBRT for prostate cancer is a small but detectable risk factor for mesothelioma. Patients should be advised of risk of radiation-induced second malignancies.}, } @article {pmid23695414, year = {2013}, author = {Tarrés, J and Albertí, C and Martínez-Artés, X and Abós-Herràndiz, R and Rosell-Murphy, M and García-Allas, I and Krier, I and Cantarell, G and Gallego, M and Canela-Soler, J and Orriols, R}, title = {Pleural mesothelioma in relation to meteorological conditions and residential distance from an industrial source of asbestos.}, journal = {Occupational and environmental medicine}, volume = {70}, number = {8}, pages = {588-590}, doi = {10.1136/oemed-2012-101198}, pmid = {23695414}, issn = {1470-7926}, mesh = {Aged ; Air Pollutants/adverse effects ; Asbestos/*adverse effects ; Chemical Industry ; Construction Materials ; Environmental Exposure/*adverse effects ; Female ; Humans ; Incidence ; *Industry ; Lung Neoplasms/epidemiology/*etiology ; Male ; Mesothelioma/epidemiology/*etiology ; Middle Aged ; *Residence Characteristics ; Retrospective Studies ; Risk Factors ; Spain/epidemiology ; *Wind ; }, abstract = {OBJECTIVES: Few studies have focused on pleural mesothelioma and environmental exposure in individuals residing around an industrial source of asbestos. The aim of this study is to determine whether residential distance and wind conditions are related to the risk of developing pleural mesothelioma.

METHODS: In this retrospective cohort study carried out in an area of Barcelona province (Catalonia, Spain), 24 environmental pleural mesothelioma cases were diagnosed between 2000 and 2009. We calculated the age-standardised incidence rate ratios of developing this disease in the population studied, taking into account the residential distance from the plant. For cases living within a 500-m radius of the plant, the geographical location in relation to the factory was also assessed.

RESULTS: The incidence rate of environmental pleural mesothelioma was higher in the population living within 500 m of the plant than in those living in a radius of 500-2000 m and much higher than those living at 2000-10 000 m. The highest incidence rate ratio for pleural mesothelioma (161.9) was found in the southeast quadrant of the 500-m area, coinciding with the predominant wind direction.

CONCLUSIONS: Residential distance from an industrial source of asbestos and local wind conditions have a considerable impact on the risk of developing environmental pleural mesothelioma.}, } @article {pmid23687495, year = {2013}, author = {Gutzeit, A and Reischauer, C and Hergan, K and Kos, S and Roos, JE}, title = {Secondary malignant peritoneal mesothelioma of the greater omentum after therapy for primary pleural mesothelioma.}, journal = {Case reports in oncology}, volume = {6}, number = {1}, pages = {236-241}, pmid = {23687495}, issn = {1662-6575}, abstract = {Mesothelioma is the most common malignant primary tumor of the pleura and usually associated with inhalation of asbestos fibers. In contrast, peritoneal mesothelioma is a rare entity whose pathomechanism is not yet fully understood. The coexistence of pleural mesothelioma with secondary involvement of the abdominal cavity has not been addressed in the literature. In this case report, we describe secondary malignant mesothelioma of the greater omentum. A 69-year-old man with histologically proven pleural mesothelioma on the right side and no past medical history of asbestos exposure received palliative treatment consisting of a talc pleurodesis. After a 6-month interval of stable disease, a local progressive tumor of the right pleura was seen on a CT scan. Eleven months later, during follow-up, the patient presented at our emergency department with a sudden onset of diffuse abdominal pain. Abdominal ultrasound revealed a mass within the greater omentum and the coexistence of free fluid. Subsequent abdominal CT scans demonstrated tumor infiltration from the right pleura by a transdiaphragmatic route into the abdomen, where diffuse infiltration of the greater omentum was observed. Aspiration of the ascites and the biopsy of the greater omentum confirmed the diagnosis of secondary malignant mesothelioma of the peritoneum. In conclusion, we present the extremely rare diagnosis of secondary malignant mesothelioma of the abdomen, which arose as a result of local progression from the right pleura into the abdomen.}, } @article {pmid23685846, year = {2013}, author = {Tabata, C and Kanemura, S and Tabata, R and Masachika, E and Shibata, E and Otsuki, T and Nishizaki, T and Nakano, T}, title = {Serum HMGB1 as a diagnostic marker for malignant peritoneal mesothelioma.}, journal = {Journal of clinical gastroenterology}, volume = {47}, number = {8}, pages = {684-688}, doi = {10.1097/MCG.0b013e318297fa65}, pmid = {23685846}, issn = {1539-2031}, mesh = {Aged ; Asbestos/toxicity ; Asbestosis/blood/diagnosis/pathology ; Biomarkers, Tumor/*blood ; Case-Control Studies ; Female ; HMGB1 Protein/*blood ; Humans ; Male ; Mesothelioma/blood/*diagnosis/pathology ; Middle Aged ; Peritoneal Neoplasms/blood/*diagnosis/pathology ; }, abstract = {BACKGROUND: Diffuse malignant peritoneal mesothelioma (DMPM) is an aggressive malignant tumor of mesothelial origin that shows a limited response to cytoreductive surgery along with intraperitoneal chemotherapy. Therefore, early diagnosis of DMPM is very important. Some researchers have previously reported that high-mobility group box 1 (HMGB1) was correlated with pulmonary fibrosis. DMPM involves the malignant transformation of mesothelial cells, which originate from mesenchymal cells, similar to lung fibroblasts. Here, we investigated serum levels of HMGB1 in patients with MPM and compared them with those of a population that had been exposed to asbestos without developing MPM.

STUDY: The serum concentrations of HMGB1 were measured in 13 DMPM patients and 45 individuals with benign asbestos-related diseases.

RESULT: We demonstrated that the patients with DMPM had significantly higher serum levels of HMGB1 compared with the population who had been exposed to asbestos but did not develop DMPM.

CONCLUSION: Our data suggest that serum HMGB1 concentration is a useful serum marker for DMPM.}, } @article {pmid23684920, year = {2013}, author = {Knipscheer, BJ and Kromontono, RC and de Bruin, PC and van Strijen, MJ and Herder, GJ}, title = {Two malignancies or an unusual presentation of a pleural malignancy?.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {81}, number = {2}, pages = {306-307}, doi = {10.1016/j.lungcan.2013.04.002}, pmid = {23684920}, issn = {1872-8332}, mesh = {Bone Neoplasms/diagnosis/*pathology ; Diagnosis, Differential ; Humans ; Lung Neoplasms/diagnosis/*pathology ; Male ; Mesothelioma/diagnosis/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/diagnosis/*pathology ; }, abstract = {Malignant mesothelioma is primarily located in the pleura. Progression usually involves adjacent tissue invasion. Both lymphatic and haematogenous spreads are possible, but rare. Bone involvement usually means locally invasive disease and rarely bone marrow metastases. In this report we presented two patients with a mesothelioma and bone marrow metastases.}, } @article {pmid23684272, year = {2013}, author = {Frank, AL}, title = {Why countries ban asbestos: some alternative thoughts.}, journal = {International journal of occupational and environmental health}, volume = {19}, number = {2}, pages = {136}, doi = {10.1179/1077352513Z.00000000060}, pmid = {23684272}, issn = {1077-3525}, mesh = {Air Pollutants/*toxicity ; Air Pollution, Indoor/*legislation & jurisprudence ; Asbestos/*toxicity ; Delivery of Health Care/*organization & administration ; Humans ; *International Cooperation ; Mesothelioma/*epidemiology ; *Policy ; }, } @article {pmid23684271, year = {2013}, author = {Bahk, J and Choi, Y and Lim, S and Paek, D}, title = {Why some, but not all, countries have banned asbestos.}, journal = {International journal of occupational and environmental health}, volume = {19}, number = {2}, pages = {127-135}, doi = {10.1179/2049396712Y.0000000011}, pmid = {23684271}, issn = {1077-3525}, mesh = {Air Pollutants/*toxicity ; Air Pollution, Indoor/*legislation & jurisprudence ; Asbestos/*toxicity ; Delivery of Health Care/*organization & administration ; Health Services Accessibility ; Humans ; *International Cooperation ; Mesothelioma/*epidemiology/mortality ; *Policy ; }, abstract = {BACKGROUND: Out of 143 countries that consumed asbestos between 2003 and 2007, only 44 have banned asbestos. This study tried to explain why some countries have banned asbestos while others have not, based on a synthesis that asbestos ban policy of a country will rely on a process of cognition of threats and exploration of safer alternatives.

METHOD: As we hypothesized that increased social cost of mesothelioma, capacity of health-related infrastructures, and policy diffusion from adjacent countries were related to asbestos ban adoption, published databases of asbestos ban years, mesothelioma mortality, country rankings in health care and human rights standings, and distribution of banning countries over 14 regions were analyzed accordingly.

RESULTS: The average mesothelioma death rate was significantly higher for countries with asbestos bans than in those with no ban (4·59 versus 1·83/million). No-ban countries had less well-developed health-related infrastructures. Among European countries, there was a tendency toward geographical diffusion of asbestos ban policy from Nordic to Western and then other European countries over the years. Even though aberrant cases were also noted where bans were instituted even without mesothelioma database, these were rather exceptions than rules.

CONCLUSION: Risk cognition is a complex process, but the presence of well-functioning health infrastructures, as well as the increased social cost of mesothelioma, that can make the plight of asbestos victims visible to the eyes of public and policy makers, may have contributed to this process. Asbestos ban policy from adjacent countries might have facilitated the adoption of alternative solutions.}, } @article {pmid23682089, year = {2013}, author = {Fayed, HE and Woodcock, VK and Grayez, J}, title = {Simultaneous bilateral spontaneous hydropneumothorax: a rare presentation of bilateral malignant pleural mesothelioma.}, journal = {BMJ case reports}, volume = {2013}, number = {}, pages = {}, pmid = {23682089}, issn = {1757-790X}, mesh = {Aged ; Humans ; Hydropneumothorax/*diagnosis/etiology ; Lung Neoplasms/complications/*diagnosis ; Male ; Mesothelioma/complications/*diagnosis ; Mesothelioma, Malignant ; Pleural Neoplasms/complications/*diagnosis ; Thoracic Surgery, Video-Assisted ; Tomography, X-Ray Computed ; }, abstract = {This is a case of a 69-year-old man with a history of asbestos exposure who presented with acute shortness of breath. His chest x-ray showed bilateral hydropneumothorax. Further investigations including CT chest and video-assisted thoracoscopic surgery revealed bilateral pleural thickening and histology confirmed epithelioid mesothelioma. This case highlights the need for clinicians to be aware of atypical presentations of malignant pleural mesothelioma as well as the importance of considering underlying secondary causes such as malignancy in the older patient presenting with spontaneous pneumo/hydropneumothorax.}, } @article {pmid23677068, year = {2013}, author = {Sekido, Y}, title = {Molecular pathogenesis of malignant mesothelioma.}, journal = {Carcinogenesis}, volume = {34}, number = {7}, pages = {1413-1419}, doi = {10.1093/carcin/bgt166}, pmid = {23677068}, issn = {1460-2180}, mesh = {Asbestos/*adverse effects ; Cell Transformation, Neoplastic/chemically induced/genetics/pathology ; Disease Progression ; Disease Susceptibility/pathology ; Epigenesis, Genetic ; *Gene Expression Regulation, Neoplastic ; Gene Frequency ; Genes, p16 ; Humans ; Mesothelioma/chemically induced/genetics/*pathology ; Neurofibromin 2/genetics/metabolism ; TOR Serine-Threonine Kinases/genetics/metabolism ; Tumor Suppressor Proteins/genetics/*metabolism ; Ubiquitin Thiolesterase/genetics/*metabolism ; }, abstract = {Malignant mesothelioma (MM) is an aggressive tumor arising primarily from the pleural or peritoneal cavities. It develops by asbestos exposure after a long latency, which is characterized by insidious growth and clinical presentation at an advanced stage of disease. MM is highly refractory to conventional therapies even with a combination of aggressive surgical intervention and multimodality strategies, with cure remaining elusive. Molecular genetic analysis has revealed several key genetic alterations, which are responsible for the development and progression of MM. The cyclin-dependent kinase inhibitor 2A/alternative reading frame (CDKN2A/ARF), neurofibromatosis type 2 (NF2) and BRCA1-associated protein-1 (BAP1) genes are the most frequently mutated tumor suppressor genes detected in MM cells; the alterations of the latter two are relatively characteristic of MM. Merlin, which is encoded by NF2, regulates multiple cell signaling cascades including the Hippo and mammalian target of rapamycin pathways, which regulate cell proliferation and growth. BAP1 is involved in histone modification and its inactivation induces the disturbance of global gene expression profiling. The discovery of a new familial cancer syndrome with germline mutation of BAP1 also indicates the importance of genetic factors in MM susceptibility. Meanwhile, although frequent expression and functional activations of oncogene products such as receptor tyrosine kinases are observed in MM cells, activating mutations of these genes are rare. With further comprehensive genome analyses, new genetic and epigenetic alterations in MM cells are expected to be revealed more precisely, and the new knowledge based on them will be applied for developing new diagnostic tools and new target therapies against MMs.}, } @article {pmid23676545, year = {2013}, author = {Busto Martin, L and Portela Pereira, P and Sacristan Lista, F and Busto Castañon, L}, title = {Mesothelioma of the tunica vaginalis. Case report.}, journal = {Archivos espanoles de urologia}, volume = {66}, number = {4}, pages = {384-388}, pmid = {23676545}, issn = {1576-8260}, mesh = {Biomarkers, Tumor/blood ; Humans ; Immunohistochemistry ; Male ; Mesothelioma/*pathology/surgery ; Middle Aged ; Orchiectomy ; Scrotum/*pathology/surgery ; Testicular Hydrocele/diagnostic imaging/pathology/surgery ; Testicular Neoplasms/*pathology/surgery ; Tomography, X-Ray Computed ; Treatment Outcome ; }, abstract = {OBJECTIVE: To report a case of a mesothelioma of the tunica vaginalis and to review the published literature. METHODS / RESULTS: A 61-year-old patient complained of one-month increase of right scrotum size with pain. An ultrasound showed a right hydrocele with a mass attached to the tunica vaginalis. He didn't refer any urological history or known exposure to asbestos. Blood levels of tumor markers (alpha-fetoprotein and beta-HCG) were within normal limits. We performed a radical inguinal orchiectomy with an en-bloc resection of the tunica vaginalis. The pathology described a potentially malignant biphasic mesothelioma. The patient has remained asymptomatic with negative extension studies after 10 years of follow up.

CONCLUSIONS: Paratesticular mesotheliomas are rare tumors (approximately 250 cases reported)with uncertain etiology (only 30-40% are associated with asbestos exposure). The age range is between 50-70 years. Its presentation is usually as a scrotal mass with recurrent reactive hydrocele, which may delay early diagnosis. During surgery, intraoperative biopsy is recommended. It is important to do a differential diagnosis with other benign diseases. Treatment is only curative in early stages with radical orchidectomy and resection in-block of the tunica vaginalis. Despite being multidisciplinary, it is not curative in most cases due to rapid local and distant spread.}, } @article {pmid23672436, year = {2013}, author = {Taylor, ES and Wylie, AG and Mossman, BT and Lower, SK}, title = {Repetitive dissociation from crocidolite asbestos acts as persistent signal for epidermal growth factor receptor.}, journal = {Langmuir : the ACS journal of surfaces and colloids}, volume = {29}, number = {21}, pages = {6323-6330}, doi = {10.1021/la400561t}, pmid = {23672436}, issn = {1520-5827}, mesh = {Asbestos, Crocidolite/*chemistry ; Cell Line, Tumor ; ErbB Receptors/*chemistry ; Humans ; Particle Size ; Surface Properties ; }, abstract = {Mesothelioma is an incurable form of cancer located most commonly in the pleural lining of the lungs and is associated almost exclusively with the inhalation of asbestos. The binding of asbestos to epidermal growth factor receptor (EGFR), a transmembrane signal protein, has been proposed as a trigger for downstream signaling of kinases and expression of genes involved in cell proliferation and inhibition of apoptosis. Here, we investigate the molecular binding of EGFR to crocidolite (blue asbestos; Na2(Fe(2+),Mg)3Fe2(3+)Si8O22(OH)2) in buffer solution. Atomic force microscopy measurements revealed an attractive force of interaction (i.e., bond) as EGFR was pulled from contact with long fibers of crocidolite. The rupture force of this bond increased with loading rate. According to the Bell model, the off-rate of bond dissociation (k(off)) for EGFR was 22 s(-1). Similar experiments with riebeckite crystals, the nonasbestiform variety of crocidolite, yielded a k(off) of 8 s(-1). These k(off) values on crocidolite and riebeckite are very rapid compared to published values for natural agonists of EGFR like transforming growth factor and epidermal growth factor. This suggests binding of EGFR to the surfaces of these minerals could elicit a response that is more potent than biological hormone or cytokine ligands. Signal transduction may cease for endogenous ligands due to endocytosis and subsequent degradation, and even riebeckite particles can be cleared from the lungs due to their short, equant habit. However, the fibrous habit of crocidolite leads to lifelong persistence in the lungs where aberrant, repetitious binding with EGFR may continually trigger the activation switch leading to chronic expression of genes involved in oncogenesis.}, } @article {pmid23667371, year = {2013}, author = {Eom, M and Abdul-Ghafar, J and Park, SM and Han, JH and Hong, SW and Kwon, KY and Ko, ES and Kim, L and Kim, WS and Ha, SY and Lee, KY and Lee, CH and Yoon, HK and Choi, YD and Chung, MJ and Jung, SH}, title = {No detection of simian virus 40 in malignant mesothelioma in Korea.}, journal = {Korean journal of pathology}, volume = {47}, number = {2}, pages = {124-129}, pmid = {23667371}, issn = {1738-1843}, abstract = {BACKGROUND: Simian virus 40 (SV40), a polyomavirus, was discovered as a contaminant of a human polio vaccine in the 1960s. It is known that malignant mesothelioma (MM) is associated with SV40, and that the virus works as a cofactor to the carcinogenetic effects of asbestos. However, the reports about the correlation between SV40 and MM have not been consistent. The purpose of this study is to identify SV40 in MM tissue in Korea through detection of SV40 protein and DNA.

METHODS: We analyzed 62 cases of available paraffin-blocks enrolled through the Korean Malignant Mesothelioma Surveillance System and performed immunohistochemistry for SV40 protein and real-time polymerase chain reaction (PCR) for SV40 DNA.

RESULTS: Of 62 total cases, 40 had disease involving the pleura (64.5%), and 29 (46.8%) were found to be of the epithelioid subtype. Immunostaining demonstrated that all examined tissues were negative for SV40 protein. Sufficient DNA was extracted for real-time PCR analysis from 36 cases. Quantitative PCR of these samples showed no increase in SV40 transcript compared to the negative controls.

CONCLUSIONS: SV40 is not associated with the development of MM in Korea.}, } @article {pmid23661263, year = {2013}, author = {Zhang, J and Cole, SR and Richardson, DB and Chu, H}, title = {A Bayesian approach to strengthen inference for case-control studies with multiple error-prone exposure assessments.}, journal = {Statistics in medicine}, volume = {32}, number = {25}, pages = {4426-4437}, pmid = {23661263}, issn = {1097-0258}, support = {P30 CA077598/CA/NCI NIH HHS/United States ; R01 CA117841/CA/NCI NIH HHS/United States ; R01-CA117841/CA/NCI NIH HHS/United States ; }, mesh = {Asbestos/*adverse effects ; Bayes Theorem ; *Bias ; *Case-Control Studies ; Data Interpretation, Statistical ; Humans ; Likelihood Functions ; Linear Models ; Mesothelioma/*etiology ; Occupational Exposure/*adverse effects/statistics & numerical data ; Probability ; Regression Analysis ; }, abstract = {In case-control studies, exposure assessments are almost always error-prone. In the absence of a gold standard, two or more assessment approaches are often used to classify people with respect to exposure. Each imperfect assessment tool may lead to misclassification of exposure assignment; the exposure misclassification may be differential with respect to case status or not; and, the errors in exposure classification under the different approaches may be independent (conditional upon the true exposure status) or not. Although methods have been proposed to study diagnostic accuracy in the absence of a gold standard, these methods are infrequently used in case-control studies to correct exposure misclassification that is simultaneously differential and dependent. In this paper, we proposed a Bayesian method to estimate the measurement-error corrected exposure-disease association, accounting for both differential and dependent misclassification. The performance of the proposed method is investigated using simulations, which show that the proposed approach works well, as well as an application to a case-control study assessing the association between asbestos exposure and mesothelioma.}, } @article {pmid23626745, year = {2013}, author = {Lesterhuis, WJ and Salmons, J and Nowak, AK and Rozali, EN and Khong, A and Dick, IM and Harken, JA and Robinson, BW and Lake, RA}, title = {Synergistic effect of CTLA-4 blockade and cancer chemotherapy in the induction of anti-tumor immunity.}, journal = {PloS one}, volume = {8}, number = {4}, pages = {e61895}, pmid = {23626745}, issn = {1932-6203}, mesh = {Animals ; Antibodies, Monoclonal/*pharmacology ; CD4-Positive T-Lymphocytes/drug effects/immunology/pathology ; CD8-Positive T-Lymphocytes/drug effects/immunology/pathology ; Carcinoma, Lewis Lung/*drug therapy/immunology/mortality/pathology ; Deoxycytidine/*analogs & derivatives/pharmacology ; Drug Synergism ; Drug Therapy, Combination ; Immunity, Innate/*drug effects ; Immunologic Factors/*pharmacology ; Lung Neoplasms/*drug therapy/immunology/mortality/pathology ; Lymphocyte Depletion ; Mesothelioma/*drug therapy/immunology/mortality/pathology ; Mice ; Mice, Transgenic ; Neoplasm Transplantation ; Survival Analysis ; Tumor Burden/drug effects ; Gemcitabine ; }, abstract = {Several chemotherapeutics exert immunomodulatory effects. One of these is the nucleoside analogue gemcitabine, which is widely used in patients with lung cancer, ovarian cancer, breast cancer, mesothelioma and several other types of cancer, but with limited efficacy. We hypothesized that the immunopotentiating effects of this drug are partly restrained by the inhibitory T cell molecule CTLA-4 and thus could be augmented by combining it with a blocking antibody against CTLA-4, which on its own has recently shown beneficial clinical effects in the treatment of patients with metastatic melanoma. Here we show, using two non-immunogenic murine tumor models, that treatment with gemcitabine chemotherapy in combination with CTLA-4 blockade results in the induction of a potent anti-tumor immune response. Depletion experiments demonstrated that both CD4(+) and CD8(+) T cells are required for optimal therapeutic effect. Mice treated with the combination exhibited tumor regression and long-term protective immunity. In addition, we show that the efficacy of the combination is moderated by the timing of administration of the two agents. Our results show that immune checkpoint blockade and cytotoxic chemotherapy can have a synergistic effect in the treatment of cancer. These results provide a basis to pursue combination therapies with anti-CTLA-4 and immunopotentiating chemotherapy and have important implications for future studies in cancer patients. Since both drugs are approved for use in patients our data can be immediately translated into clinical trials.}, } @article {pmid23626673, year = {2013}, author = {Matullo, G and Guarrera, S and Betti, M and Fiorito, G and Ferrante, D and Voglino, F and Cadby, G and Di Gaetano, C and Rosa, F and Russo, A and Hirvonen, A and Casalone, E and Tunesi, S and Padoan, M and Giordano, M and Aspesi, A and Casadio, C and Ardissone, F and Ruffini, E and Betta, PG and Libener, R and Guaschino, R and Piccolini, E and Neri, M and Musk, AW and de Klerk, NH and Hui, J and Beilby, J and James, AL and Creaney, J and Robinson, BW and Mukherjee, S and Palmer, LJ and Mirabelli, D and Ugolini, D and Bonassi, S and Magnani, C and Dianzani, I}, title = {Genetic variants associated with increased risk of malignant pleural mesothelioma: a genome-wide association study.}, journal = {PloS one}, volume = {8}, number = {4}, pages = {e61253}, pmid = {23626673}, issn = {1932-6203}, mesh = {Aged ; Asbestos/*adverse effects ; Australia ; Case-Control Studies ; Female ; *Genetic Loci ; Genetic Markers ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Italy ; Male ; Mesothelioma/etiology/*genetics ; Middle Aged ; Neoplasm Proteins/*genetics ; Occupational Exposure/*adverse effects ; Odds Ratio ; Pleural Neoplasms/etiology/*genetics ; Polymorphism, Single Nucleotide ; Risk Factors ; }, abstract = {Asbestos exposure is the main risk factor for malignant pleural mesothelioma (MPM), a rare aggressive tumor. Nevertheless, only 5-17% of those exposed to asbestos develop MPM, suggesting the involvement of other environmental and genetic risk factors. To identify the genetic risk factors that may contribute to the development of MPM, we conducted a genome-wide association study (GWAS; 370,000 genotyped SNPs, 5 million imputed SNPs) in Italy, among 407 MPM cases and 389 controls with a complete history of asbestos exposure. A replication study was also undertaken and included 428 MPM cases and 1269 controls from Australia. Although no single marker reached the genome-wide significance threshold, several associations were supported by haplotype-, chromosomal region-, gene- and gene-ontology process-based analyses. Most of these SNPs were located in regions reported to harbor aberrant alterations in mesothelioma (SLC7A14, THRB, CEBP350, ADAMTS2, ETV1, PVT1 and MMP14 genes), causing at most a 2-3-fold increase in MPM risk. The Australian replication study showed significant associations in five of these chromosomal regions (3q26.2, 4q32.1, 7p22.2, 14q11.2, 15q14). Multivariate analysis suggested an independent contribution of 10 genetic variants, with an Area Under the ROC Curve (AUC) of 0.76 when only exposure and covariates were included in the model, and of 0.86 when the genetic component was also included, with a substantial increase of asbestos exposure risk estimation (odds ratio, OR: 45.28, 95% confidence interval, CI: 21.52-95.28). These results showed that genetic risk factors may play an additional role in the development of MPM, and that these should be taken into account to better estimate individual MPM risk in individuals who have been exposed to asbestos.}, } @article {pmid23624458, year = {2013}, author = {Singh, A and Chatterjee, P and Pai, MC and Chacko, RT}, title = {Multicystic peritoneal mesothelioma: not always a benign disease.}, journal = {Singapore medical journal}, volume = {54}, number = {4}, pages = {e76-8}, doi = {10.11622/smedj.2013085}, pmid = {23624458}, issn = {2737-5935}, mesh = {Adult ; Cell Differentiation ; Diagnosis, Differential ; Female ; Humans ; Mesothelioma, Cystic/*diagnosis ; Neoplasm Metastasis ; Ovarian Neoplasms/diagnosis ; Ovary/pathology ; Peritoneal Neoplasms/*diagnosis ; Reproducibility of Results ; Tomography, X-Ray Computed ; }, abstract = {Mesothelioma is a slow-growing insidious lesion of neoplastic aetiology arising from the pleural, peritoneal or pericardial mesothelium. It shows a predilection for the surfaces of the pelvic viscera and has a high rate of recurrence after excision. Cystic mesotheliomas are not associated with asbestos exposure. We report a case of cystic mesothelioma of the peritoneum encasing the ovary, which presented as a cystic adnexal mass. As highlighted in this case and other recent reports, a cystic mesothelioma should not be referred to as a benign cystic mesothelioma, as it has potential for locoregional invasion, as well as distant nodal and serosal metastases. This tumour should be treated with aggressive cytoreductive surgery and appropriate chemotherapy. We review the differential diagnosis of this rare entity and suggest guidelines for its differentiation.}, } @article {pmid23621518, year = {2013}, author = {Okazaki, Y and Nagai, H and Chew, SH and Li, J and Funahashi, S and Tsujimura, T and Toyokuni, S}, title = {CD146 and insulin-like growth factor 2 mRNA-binding protein 3 predict prognosis of asbestos-induced rat mesothelioma.}, journal = {Cancer science}, volume = {104}, number = {8}, pages = {989-995}, pmid = {23621518}, issn = {1349-7006}, mesh = {Animals ; Asbestos/*toxicity ; Biomarkers, Tumor/*biosynthesis/genetics/metabolism ; CD146 Antigen/*biosynthesis/genetics/metabolism ; Cyclin D1/genetics/metabolism ; Female ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics/metabolism ; Immunohistochemistry/methods ; Insulin-Like Growth Factor Binding Protein 3/*biosynthesis/genetics/metabolism ; Ki-67 Antigen/genetics/metabolism ; Male ; Mesothelioma/etiology/genetics/*metabolism/pathology ; Peritoneal Neoplasms/etiology/genetics/*metabolism/pathology ; Prognosis ; RNA, Messenger/genetics/metabolism ; Rats ; Rats, Inbred BN ; }, abstract = {Malignant mesothelioma (MM), which is associated with asbestos exposure, is one of the most deadly tumors in humans. Early MM is concealed in the serosal cavities and lacks specific clinical symptoms. For better treatment, early detection and prognostic markers are necessary. Recently, CD146 and insulin-like growth factor 2 mRNA-binding protein 3 (IMP3) were reported as possible positive markers of MM to distinguish from reactive mesothelia in humans. However, their application on MM of different species and its impact on survival remain to be elucidated. To disclose the utility of these molecules as early detection and prognostic markers of MM, we injected chrysotile or crocidolite intraperitoneally to rats, thus obtaining 26 peritoneal MM and establishing 11 cell lines. We immunostained CD146 and IMP3 using paraffin-embedded tissues and cell blocks and found CD146 and IMP3 expression in 58% (15/26) and 65% (17/26) of MM, respectively, but not in reactive mesothelia. There was no significant difference in both immunostainings for overexpression among the three histological subtypes of MM and the expression of CD146 and IMP3 was proportionally associated. Furthermore, the overexpression of CD146 and/or IMP3 was proportionally correlated with shortened survival. These results suggest that CD146 and IMP3 are useful diagnostic and prognostic markers of MM.}, } @article {pmid23617783, year = {2013}, author = {Tabata, C and Shibata, E and Tabata, R and Kanemura, S and Mikami, K and Nogi, Y and Masachika, E and Nishizaki, T and Nakano, T}, title = {Serum HMGB1 as a prognostic marker for malignant pleural mesothelioma.}, journal = {BMC cancer}, volume = {13}, number = {}, pages = {205}, pmid = {23617783}, issn = {1471-2407}, mesh = {Adenocarcinoma/*blood ; Aged ; Area Under Curve ; Asbestosis/blood ; Biomarkers, Tumor/*blood ; Carcinoma, Squamous Cell/*blood ; Case-Control Studies ; Cell Line, Tumor ; Female ; HMGB1 Protein/*blood/metabolism ; Humans ; Kaplan-Meier Estimate ; Lung Neoplasms/*blood ; Male ; Mesothelioma/*blood/metabolism/pathology ; Middle Aged ; Pleural Neoplasms/*blood/metabolism/pathology ; Proportional Hazards Models ; ROC Curve ; Statistics, Nonparametric ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive malignant tumor of mesothelial origin that shows a limited response to conventional chemotherapy and radiotherapy. Therefore, diagnosing MPM early is very important. Some researchers have previously reported that high-mobility group box 1 (HMGB1) was correlated with pulmonary fibrosis. MPM involves the malignant transformation of mesothelial cells, which originate from mesenchymal cells similar to lung fibroblasts. Here, we investigated serum levels of HMGB1 in patients with MPM and compared them with those of a population that had been exposed to asbestos without developing MPM.

METHODS: HMGB1 production from MPM cell lines was measured using ELISA. Serum HMGB1 levels were also examined in 61 MPM patients and 45 individuals with benign asbestos-related diseases.

RESULTS: HMGB1 concentrations of 2 out of 4 MPM cell lines were higher than that of normal mesothelial cell line, Met-5A. We demonstrated that patients with MPM had significantly higher serum levels of HMGB1 than the population who had been exposed to asbestos but had not developed MPM. The difference in overall survival between groups with serum HMGB1 levels that were lower and higher than assumed cut-off values was significant.

CONCLUSIONS: Our data suggest that serum HMGB1 concentration is a useful prognostic factor for MPM.}, } @article {pmid23609252, year = {2013}, author = {Baççioğlu, A and Kaba, E and Ozmen, SA and Demirci, M}, title = {Desmoplastic malignant mesothelioma.}, journal = {Journal of bronchology & interventional pulmonology}, volume = {20}, number = {2}, pages = {155-158}, doi = {10.1097/LBR.0b013e31828e1aa2}, pmid = {23609252}, issn = {1948-8270}, mesh = {Aged ; Female ; Humans ; Mesothelioma/*pathology ; Pleural Neoplasms/*pathology ; }, abstract = {Desmoplastic mesothelioma is a rare subtype of diffuse malignant mesothelioma. A 72-year-old woman from East Anatolia presented with chest pain. The images of body positron emission tomography revealed irregular, left pleural thickening involving mediastinal and diaphragmatic surfaces with hypermetabolic characterization. The diagnosis of desmoplastic malignant mesothelioma was confirmed by minithoracotomy and immunohistochemical staining with pan-cytokeratin, cytokeratin 5/6, calretinin, carcinoembryonic antigen, thyroid transcription factor-1, CD15, and HMB-45 on the biopsy specimen. This case is unique in terms of the reporting patient being from a nonendemic area for asbestos-related diseases and in terms of its rare histopathology.}, } @article {pmid23606987, year = {2013}, author = {Melnikova, N and Wu, J and Kaye, W and Orr, M}, title = {Reliability of Family Proxy Data for Studies of Malignant Mesothelioma: Results from the ATSDR Pilot Surveillance.}, journal = {ISRN oncology}, volume = {2013}, number = {}, pages = {325409}, pmid = {23606987}, issn = {2090-5661}, abstract = {Objective. To evaluate the validity of proxy interviews in obtaining information on persons with rapidly fatal diseases such as malignant mesothelioma (MM). Methods. Persons with MM diagnosed in 2002 through 2005 in New York and New Jersey and 1997-2004 in Wisconsin were eligible for inclusion in the project. Persons with MM and their family member proxy were interviewed using the same questionnaire designed by ATSDR to collect information on potential direct or indirect occupational and environmental exposure to asbestos, genetic, and health related malignancy predisposition, and exposure to tobacco products. Descriptive statistics and the McNemar/Durkalski test were used to analyze 33 matched pairs. Results. The overall study confirmed a generally high ability of proxies to give interviews of comparable quality and completeness when asked dichotomous questions. The reliability of information collected from proxies varied by topic and family relationship. Conclusions. Family proxy interviews, using dichotomous responses, can serve as an acceptable source of information about health and exposure-related risk factors for MM.}, } @article {pmid23595591, year = {2013}, author = {Blum, W and Schwaller, B}, title = {Calretinin is essential for mesothelioma cell growth/survival in vitro: a potential new target for malignant mesothelioma therapy?.}, journal = {International journal of cancer}, volume = {133}, number = {9}, pages = {2077-2088}, doi = {10.1002/ijc.28218}, pmid = {23595591}, issn = {1097-0215}, mesh = {Animals ; Apoptosis/drug effects ; Blotting, Western ; Calbindin 2 ; Cell Cycle ; Cell Proliferation ; Cells, Cultured ; Epithelium/metabolism/*pathology ; Humans ; In Vitro Techniques ; Lentivirus/genetics ; Mesothelioma/metabolism/*pathology ; Mice ; Pleural Neoplasms/metabolism/*pathology ; Proto-Oncogene Proteins c-akt/metabolism ; RNA, Small Interfering/genetics ; S100 Calcium Binding Protein G/antagonists & inhibitors/genetics/*metabolism ; Sarcoma/metabolism/*pathology ; }, abstract = {Malignant mesothelioma (MM) are highly aggressive asbestos-related neoplasms, which show strong chemotherapy resistance, and there is no effective cure for MM so far. Calretinin (CR) is widely used as a diagnostic marker for epithelioid and mixed (biphasic) mesothelioma; however, little is known about CR's putative functions in tumorigenesis. CR protects against asbestos-induced acute cytotoxicity mediated by the AKT/PI3K pathway, and furthermore, SV40 early region genes are able to upregulate CR in mesothelial cells. However, the precise role of CR in mesothelioma is still unknown. Downregulation of CR via lentiviral-mediated short-hairpin RNA significantly decreased the viability and proliferation of mesothelioma cells in vitro. The effect was strong in epithelioid-dominated cell lines (ZL55 and MSTO-211H). A weaker and delayed effect was observed in mesothelioma cells with prevalent sarcomatoid morphology (SPC111, SPC212 and ZL34). The specificity of the effect was confirmed by stable enhanced green fluorescent protein-CR expression in mesothelioma cell lines and subsequent downregulation. Depletion of CR led these cancer cell lines to enter apoptosis within 72 hr postinfection via strong activation of the intrinsic caspase 9-dependent pathway. Downregulation of CR in immortalized mesothelial cells LP9/TERT-1 strongly blocked proliferation and caused a G1 block without decreasing viability or activating apoptosis pathways. These results demonstrate that downregulation of CR had a strong effect on the viability of MM cells and that CR is essential for cells derived from MM. The authors anticipate these findings to reveal CR as a highly interesting new putative therapeutic target for mesothelioma treatment of especially the epithelioid, as well as of the mixed and sarcomatoid type.}, } @article {pmid23585512, year = {2013}, author = {Ribeiro, C and Campelos, S and Moura, CS and Machado, JC and Justino, A and Parente, B}, title = {Well-differentiated papillary mesothelioma: clustering in a Portuguese family with a germline BAP1 mutation.}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {24}, number = {8}, pages = {2147-2150}, doi = {10.1093/annonc/mdt135}, pmid = {23585512}, issn = {1569-8041}, mesh = {Adult ; Asbestos/adverse effects ; Cluster Analysis ; Environmental Exposure ; Female ; Genetic Predisposition to Disease ; Germ-Line Mutation ; Humans ; Melanoma/*genetics ; Mesothelioma/*genetics/mortality ; Middle Aged ; Peritoneal Neoplasms/*genetics ; Pleural Neoplasms/*genetics ; Portugal ; Prognosis ; Siblings ; Survival ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; Uveal Neoplasms/*genetics ; }, abstract = {BACKGROUND: Well-differentiated papillary mesothelioma (WDPM) is a rare variant of epithelioid mesothelioma and is considered to be associated with good prognosis due to its clinically indolent behavior and long survival. Most reported cases involve the peritoneum of women at reproductive age with no history of exposure to asbestos, with pleural involvement being less common. The optimal management, including the role of chemotherapy in the treatment of WDPM, remains unsettled.

PATIENTS AND METHODS: The authors describe two cases of WDPM in women of the same family (siblings); the elder with WDPM of the pleura and peritoneum with a 12-year survival period and the younger with a WDPM of the peritoneum diagnosed in 2011 and uveal melanoma diagnosed in 2012. Neither patient had any known exposure to asbestos fibers or any other mineral carcinogens.

RESULTS: After the concurrent diagnosis of WDPM and uveal melanoma, genetic diagnosis was carried out taking into consideration that these two malignancies were recently associated with hereditary BAP1 gene mutations and it was positive for both the patients.

CONCLUSIONS: To our knowledge, this is the first description of WDPM in two siblings who also presented with a germline BAP1 mutation. This article provides evidence of the wide clinical spectrum of cancer susceptibility associated with a BAP1 germline mutation.}, } @article {pmid23585433, year = {2013}, author = {Chellini, E and Martini, A and Cacciarini, V and Badiali, AM and , }, title = {[Considerations about the epidemiologic surveillance system on mesothelioma in Tuscany (Italy) after 25 years of activity].}, journal = {Epidemiologia e prevenzione}, volume = {37}, number = {1}, pages = {43-50}, pmid = {23585433}, issn = {1120-9763}, mesh = {Asbestos/poisoning ; Epidemiological Monitoring ; Female ; Humans ; Italy/epidemiology ; Lung Neoplasms/*epidemiology/etiology ; Male ; Mesothelioma/*epidemiology/etiology ; Mesothelioma, Malignant ; Pleural Neoplasms/*epidemiology/etiology ; Registries ; Survival Analysis ; }, abstract = {OBJECTIVE AND DESIGN: To present problems and opportunities related to the operating procedures developed by the Tuscan epidemiological surveillance system on mesothelioma during its 25 years of activity.

SETTING AND PARTICIPANTS: All 1,224 mesotheliomas, registered up to 31.12. 2011, diagnosed in Tuscan residents during 1988-2009 by the Tuscan Operating Centre of the Italian registry, have been considered.

MAIN OUTCOME MEASURES: In order to evaluate accuracy and completeness of cases, the following indicators by period are used for pleural mesotheliomas diagnosed during 1988-2009: the distribution of the sources of cases' diagnosis and report to the regional registry, the latency time between diagnosis and report, the age and sex specific rates, the ratio between standardized mortality and incidence rates. The distribution of type of interview and exposure classification by period for all cases were used to evaluate the collected and classified exposure information.

RESULTS: Histology with immunohistochemistry became the chosen method (97.4% of histological cases in 2005- 2009). Since the second half of the Nineties, other Italian regional Operating Centres and, more recently, the Workers Compensation Authority (INAIL) became new important sources of case report. Nowadays, the mortality/incidence ratio is closer to 1. The latency time between diagnosis and case report have been reducing with a consequent increase in direct interviews to cases (from 20.3% in 1988-1993 to 71.4% in 2005-2009) and in exposure information and classification quality.

CONCLUSION: The regional network with the effective cooperation of the Local Health Authorities produced relevant improvements in the quality of the epidemiological surveillance system. It is hoped that the new revision of the national Guidelines will succeed in taking into consideration all the improvements made by the surveillance system in order to get over the difficulties observed in defining and classifying cases and their asbestos exposure.}, } @article {pmid23585432, year = {2013}, author = {Binazzi, A and Scarselli, A and Corfiati, M and Di Marzio, D and Branchi, C and Verardo, M and Mirabelli, D and Gennaro, V and Mensi, C and Schallenberg, G and Merler, E and De Zotti, R and Romanelli, A and Chellini, E and Pascucci, C and D'Alò, D and Forastiere, F and Trafficante, L and Menegozzo, S and Musti, M and Cauzillo, G and Leotta, A and Tumino, R and Melis, M and Marinaccio, A and , }, title = {[Epidemiologic surveillance of mesothelioma for the prevention of asbestos exposure also in non-traditional settings].}, journal = {Epidemiologia e prevenzione}, volume = {37}, number = {1}, pages = {35-42}, pmid = {23585432}, issn = {1120-9763}, mesh = {Asbestos/*poisoning ; Epidemiological Monitoring ; Female ; Humans ; Italy/epidemiology ; Lung Neoplasms/*epidemiology/etiology/prevention & control ; Male ; Mesothelioma/*epidemiology/etiology/prevention & control ; Mesothelioma, Malignant ; Middle Aged ; Occupational Diseases/*epidemiology/etiology/prevention & control ; Occupational Exposure/adverse effects ; Pleural Neoplasms/*epidemiology/etiology/prevention & control ; Population Surveillance ; Registries ; }, abstract = {OBJECTIVE: To show how malignant mesothelioma (MM) surveillance not only identifies settings of exposure representing past industrial history, but it may also detect conditions of current exposure relevant for the prevention, if the wide spectrum of asbestos uses is considered.

DESIGN: Active search of MM cases and exposure assessment at individual level through a questionnaire; identification of exposure circumstances relevant for prevention.

SETTING AND PARTICIPANTS: Italy, all the Regions where a Regional Operating Centre (COR) is established to identify all MM cases diagnosed in the population and analyze their occupational, residential, household and environmental histories. Period of diagnosis: 1993-2008.

MAIN OUTCOME MEASURES: Descriptive analysis of MM cases and of asbestos exposures.

RESULTS: ReNaM includes 15,845 cases of MM diagnosed between 1993 and 2008.The male/female ratio is 2.5. Mean age at diagnosis is 69 years. Pleural MMs represent 93% of all cases. Exposures have been investigated in 12,065 cases (76%). The median latency time is 46 years. In addition to clusters of MM cases in activities well known to entail asbestos use, different current exposure circumstances requiring intervention have been evidenced.

CONCLUSIONS: On the basis of this experience, epidemiological surveillance of all occupational cancers should be implemented to foster synergies with the compensation system and the Local Health Authorities' occupational safety and health services, as required by the Italian Legislative Decree N. 81/2008.}, } @article {pmid23582609, year = {2013}, author = {Henley, SJ and Larson, TC and Wu, M and Antao, VC and Lewis, M and Pinheiro, GA and Eheman, C}, title = {Mesothelioma incidence in 50 states and the District of Columbia, United States, 2003-2008.}, journal = {International journal of occupational and environmental health}, volume = {19}, number = {1}, pages = {1-10}, pmid = {23582609}, issn = {1077-3525}, support = {CC999999/ImCDC/Intramural CDC HHS/United States ; }, mesh = {Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Air Pollutants/*adverse effects ; Asbestos/*adverse effects ; District of Columbia/epidemiology ; Environmental Exposure/*adverse effects ; Female ; Humans ; Incidence ; Male ; Mesothelioma/*chemically induced/*epidemiology/ethnology ; Middle Aged ; Occupational Exposure/adverse effects ; Registries ; Sex Distribution ; United States/epidemiology ; }, abstract = {BACKGROUND: The decline in asbestos use in the United States may impact mesothelioma incidence.

OBJECTIVE: This report provides national and state-specific estimates of mesothelioma incidence in the United States using cancer surveillance data for the entire US population.

METHODS: Data from the National Program for Cancer Registries and the Surveillance, Epidemiology, and End Results program were used to calculate incidence rates and annual percent change.

RESULTS: During 2003-2008, an average of 1.05 mesothelioma cases per 100 000 persons were diagnosed annually in the United States; the number of cases diagnosed each year remained level, whereas rates decreased among men and were stable among women.

CONCLUSION: US population-based cancer registry data can be used to determine the burden of mesothelioma and track its decline. Even 30 years after peak asbestos use in the United States, 3200 mesothelioma cases are diagnosed annually, showing that the US population is still at risk.}, } @article {pmid23582574, year = {2013}, author = {Döngel, I and Bayram, M and Bakan, ND and Yalçın, H and Gültürk, S}, title = {Is living close to ophiolites related to asbestos related diseases? Cross-sectional study.}, journal = {Respiratory medicine}, volume = {107}, number = {6}, pages = {870-874}, doi = {10.1016/j.rmed.2013.03.006}, pmid = {23582574}, issn = {1532-3064}, mesh = {Adult ; Age Factors ; Aged ; Asbestos/analysis/*toxicity ; Body Mass Index ; Carcinogens/analysis/toxicity ; Construction Materials/toxicity ; Cross-Sectional Studies ; Environmental Exposure/*adverse effects/analysis ; Female ; Housing/statistics & numerical data ; Humans ; Male ; Mesothelioma/epidemiology/*etiology ; Middle Aged ; Pleural Diseases/epidemiology/*etiology ; Residence Characteristics ; Risk Factors ; Sex Factors ; Soil/analysis ; Turkey/epidemiology ; }, abstract = {OBJECTIVE: To determine the rate of pleural plaques and malignant mesothelioma and other factors that affect people living close to ophiolites.

METHODS: The study population was comprised of 2970 volunteers who resided <10 km from an ophiolitic unit. Control group comprised of 157 residents >25 km from ophiolites. Information gathered from the patients included presence of pleural plaques on chest X-ray, distance from ophiolites, gender, smoking status, duration of asbestos exposure, and body mass index (BMI). Mineralogical analysis of soil and rock samples was performed by X-ray diffraction.

RESULTS: Among the 2970 study participants, those who lived close to ophiolites, 9.8% had asbestos related disease (3 malignant mesothelioma, 289 pleural plaques). No asbestos related disease (ARD) was identified in the control group. Male gender (OR: 2.63, 95% 1.9-3.5, p < 0.001), advanced age (5% increase for every year p < 0.001), residential proximity to ophiolites (for every 1 km proximity, a 12% increase p < 0.001), and low BMI (for every 1 unit decrease, 3.6% increase p < 0.001) were associated with increased risk of ARD.

CONCLUSION: The rate of ARD is higher in residents living close to ophiolites. Important risk factors for developing ARD were age, male gender, proximity to an ophiolite site, and low BMI.}, } @article {pmid23580457, year = {2013}, author = {Karabin-Kehl, B and Harth, V and Preisser, AM}, title = {[Epidemiological and occupational medicine aspects of pleural mesothelioma].}, journal = {Pneumologie (Stuttgart, Germany)}, volume = {67}, number = {4}, pages = {209-218}, doi = {10.1055/s-0032-1326061}, pmid = {23580457}, issn = {1438-8790}, mesh = {Asbestosis/*mortality/prevention & control ; Causality ; Comorbidity ; Early Diagnosis ; Environmental Monitoring/methods/*statistics & numerical data ; Germany/epidemiology ; Humans ; Incidence ; Mesothelioma/*mortality/prevention & control ; Occupational Exposure/*prevention & control/*statistics & numerical data ; Pleural Neoplasms/*mortality/prevention & control ; Risk Factors ; Survival Analysis ; Survival Rate ; }, abstract = {Malignant mesothelioma of the pleura represents a signal tumour for (occupational) exposure to asbestos. Almost 20 years after the ban of asbestos in Germany, incident cases are still occurring due to the long latency period between the initial exposure to asbestos and the onset of the tumour. Of particular interest is the development of mesothelioma epidemiology. In Germany, it is extensively discussed whether the incidence of malignant pleura mesothelioma continues to rise, has already reached a plateau or is expected to decline in the next few years. The development is predominantly caused by the total asbestos use, its application and the gradual substitution of asbestos. The prevention of asbestos-related diseases due to former exposures, but also due to existing asbestos contaminations and their restoration is still a hot topic in occupational medicine. It is thus of major importance to ensure an adequate occupational safety and to care for asbestos-exposed workers - even after cessation of their exposure - with effective and efficient measures of early detection. New technologies, such as nanotechnology with carbon nanotubes, represent new potential health hazards.}, } @article {pmid23576643, year = {2013}, author = {Madsen, PH and Laursen, CB and Davidsen, JR}, title = {Diagnostic delay in malignant pleural mesothelioma due to physicians fixation on history with non-exposure to asbestos.}, journal = {BMJ case reports}, volume = {2013}, number = {}, pages = {}, pmid = {23576643}, issn = {1757-790X}, mesh = {Delayed Diagnosis ; Diagnosis, Differential ; Fatal Outcome ; Female ; Humans ; Mesothelioma/*diagnosis/therapy ; Middle Aged ; Pleural Neoplasms/*diagnosis/therapy ; Radiography, Thoracic ; Thoracic Surgery, Video-Assisted ; Tomography, X-Ray Computed ; }, abstract = {To establish the diagnosis of virtually any disease, the clinician must combine a variety of information. Often emphasised in this context is thorough medical history-taking including information on exposure to factors leading to or being associated with the disease in question. Continuous assessment of all available information is of utmost importance, as fixation on single details can be misguiding with inappropriate consequences in both the diagnostic and therapeutic approach. This case report presents how an atypical medical history led to a delay in the diagnosis of malignant pleural mesothelioma due to a low a priori likelihood of the disease because of non-exposure to asbestos. We highlight the fact that postrationalisation and attempts to renew a diagnostic approach must be carried out each time diagnostic dilemmas emerge, and when some or all diagnostic clues disagree.}, } @article {pmid23571781, year = {2013}, author = {Uemoto, J and Hoshi, N and Hirabayashi, K and Hoshi, S and Onodera, K and Nishi, T and Tomikawa, M and Igarashi, S}, title = {Collision tumors of hepatocellular carcinoma and malignant peritoneal mesothelioma.}, journal = {Medical molecular morphology}, volume = {46}, number = {3}, pages = {177-183}, pmid = {23571781}, issn = {1860-1499}, mesh = {Carcinoma, Hepatocellular/*diagnostic imaging/therapy ; Combined Modality Therapy ; Fatal Outcome ; Humans ; Liver/pathology ; Liver Neoplasms/*diagnostic imaging/therapy ; Lung Neoplasms/*diagnostic imaging/therapy ; Male ; Mesothelioma/*diagnostic imaging/therapy ; Mesothelioma, Malignant ; Middle Aged ; Neoplasms, Multiple Primary/*diagnostic imaging/therapy ; Peritoneal Neoplasms/*diagnostic imaging/therapy ; Radiography ; }, abstract = {We report a case of synchronous hepatocellular carcinoma (HCC) and malignant peritoneal mesothelioma (MM-per). A 56-year-old man with no past history of asbestos exposure, chronic viral hepatitis, or alcoholic liver injury was admitted to our hospital with left flank pain and abdominal tumor. Partial hepatectomy, splenectomy, partial diaphragm resection, and partial gastrectomy were performed. The tumor in the lateral segment of the liver was gray to white, massive in appearance, and contained focal bile-producing nodules and extensive fibrous firm lesion. It had directly invaded the spleen and diaphragm. Liver cirrhosis was not found. The peritoneum contained multiple small nodules especially around the diaphragm, which mimicked carcinoma dissemination. After histological examination, the liver tumor was diagnosed as HCC. It had trabecular and scirrhous patterns and positive immunoreactivities for Hep-Par-1 and α-fetoprotein. The peritoneal nodules were diagnosed as MM-per, epithelioid type, with positive immunoreactivities for calretinin and cytokeratin 5/6. The two tumors collided around the diaphragm. Cases of MM synchronous with other primary malignant tumors have been reported, but most had a history of asbestos exposure unlike the present case. The carcinogenic background was unclear for two tumors in this case. This is an extremely rare and valuable case.}, } @article {pmid23570993, year = {2013}, author = {Treumann, S and Ma-Hock, L and Gröters, S and Landsiedel, R and van Ravenzwaay, B}, title = {Additional histopathologic examination of the lungs from a 3-month inhalation toxicity study with multiwall carbon nanotubes in rats.}, journal = {Toxicological sciences : an official journal of the Society of Toxicology}, volume = {134}, number = {1}, pages = {103-110}, doi = {10.1093/toxsci/kft089}, pmid = {23570993}, issn = {1096-0929}, mesh = {Aerosols ; Air Pollutants/pharmacokinetics/*toxicity ; Animals ; Dose-Response Relationship, Drug ; Granuloma, Respiratory Tract/chemically induced/metabolism/pathology ; Guidelines as Topic ; Inhalation Exposure ; Lipoproteins/metabolism ; Lung/*drug effects/metabolism/*ultrastructure ; Macrophages, Alveolar/diagnostic imaging/drug effects/metabolism ; Male ; Microscopy, Electron, Transmission ; Nanotubes, Carbon/*toxicity ; Neutrophil Infiltration/drug effects ; Organ Size/drug effects ; Particle Size ; Rats ; Reticulin/drug effects/metabolism/ultrastructure ; Tissue Distribution ; Toxicity Tests, Subchronic/methods ; Ultrasonography ; }, abstract = {For hazard assessment of multiwalled carbon nanotubes (MWCNTs), a 90-day inhalation toxicity study has been performed with Nanocyl NC 7000 in accordance with OECD 413 test guideline. MWCNTs produced no systemic toxicity. However, increased lung weights, multifocal granulomatous inflammation, diffuse histiocytic and neutrophilic infiltrates, and intra-alveolar lipoproteinosis were observed in lung and lung-associated lymph nodes at 0.5 and 2.5mg/m(3). Additional investigations of the lungs were performed, including special stains for examination of connective tissue, and electron microscopy was performed to determine the location of the MWCNTs. The alveolar walls revealed no increase of collagen fibers, whereas within the microgranulomas a slight increase of collagen fibers was observed. The pleura did not reveal any increase in collagen fibers. Only a slight increase in reticulin fibers in the alveolar walls in animals of the 0.5 and 2.5mg/m(3) concentration group was noted. In the 0.1mg/m(3) group, the only animal revealing minimal granulomas exhibited a minimal increase in collagen within the granuloma. No increase in reticulin was observed. Electron microscopy demonstrated entangled MWCNTs within alveolar macrophages. Occasionally electron dense particles/detritus were observed within membrane-bound vesicles (interpreted as phagosomes), which could represent degraded MWCNTs. If so, MWCNTs were degradable by alveolar macrophages and not persistent within the lung. Inhalation of MWCNTs caused granulomatous inflammation within the lung parenchyma but not the pleura in any of the concentration groups. Thus, there are some similarities to effects caused by inhaled asbestos, but the hallmark effects, namely pleural inflammation and/or fibrosis leading to mesotheliomas, are absent.}, } @article {pmid23553125, year = {2014}, author = {Berk, S and Yalcin, H and Dogan, OT and Epozturk, K and Akkurt, I and Seyfikli, Z}, title = {The assessment of the malignant mesothelioma cases and environmental asbestos exposure in Sivas province, Turkey.}, journal = {Environmental geochemistry and health}, volume = {36}, number = {1}, pages = {55-64}, pmid = {23553125}, issn = {1573-2983}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Asbestos, Amphibole ; Environmental Exposure/*adverse effects ; Female ; Geology/methods ; Housing ; Humans ; Lung Neoplasms/chemically induced/*diagnosis/*epidemiology/etiology ; Male ; Mesothelioma/chemically induced/*diagnosis/*epidemiology/etiology ; Mesothelioma, Malignant ; Microscopy, Electron, Scanning ; Middle Aged ; Turkey/epidemiology ; X-Ray Diffraction ; Young Adult ; }, abstract = {One of the most significant diseases related to environmental asbestos exposure is malignant mesothelioma (MM). Sivas province is located in the Central Anatolia where asbestos exposure is common. We aimed to study clinical, demographical and epidemiologic features of the patients with MM in Sivas, along with the history of asbestos exposure. In total, 219 patients with MM who were diagnosed in our hospital between 1993 and 2010 were retrospectively analyzed in terms of demographical and clinical features. Rock, soil and house plaster samples were taken from the habitats of those patients and were evaluated with optical microscopy and X-ray diffraction methods. The age of the patients ranged between 18 and 85 years. The male-to-female ratio was 1.4:1. Most of the patients confirmed an asbestos exposure history. The most frequent symptoms of the patients were chest pain (60 %) and dyspnea (50 %). The gap between the start of first symptoms and the diagnosis date was approximately 4 months in average. The plaster materials used in most of the houses were made up of mainly carbonate and silicate minerals and some chrysotile. Ophiolitic units contained fibrous minerals such as serpentine (clino + orthochrysotile) chiefly and pectolite, brucite, hydrotalcite and tremolite/actinolite in smaller amounts. MM is not primarily related to occupational asbestos exposure in our region, and hence, environmental asbestos exposure may be indicted. Yet, single or combined roles and/or interactions of other fibrous and non-fibrous minerals in the etiology of MM are not yet fully understood and remain to be investigated.}, } @article {pmid23550710, year = {2013}, author = {Rodriguez-Panadero, F and Romero-Romero, B}, title = {Current and future options for the diagnosis of malignant pleural effusion.}, journal = {Expert opinion on medical diagnostics}, volume = {7}, number = {3}, pages = {275-287}, doi = {10.1517/17530059.2013.786038}, pmid = {23550710}, issn = {1753-0067}, mesh = {Biomarkers/analysis ; Diagnostic Imaging/methods ; Humans ; Molecular Diagnostic Techniques/methods ; Nanomedicine/methods ; Pleural Effusion, Malignant/*diagnosis ; }, abstract = {INTRODUCTION: Malignant pleural effusion (MPE) is a frequent problem faced by clinicians, but tumor pleural involvement can be seen without effusion.

AREAS COVERED: Imaging, pleural fluid analysis, biomarkers for MPE, needle pleural biopsy and thoracoscopy. To prepare this review, we performed a search using keywords: 'diagnosis' + 'malignant' + 'pleural' + 'effusion' (all fields) in PubMed, and found 4106 articles overall (until 16 January 2013, 881 in the last 5 years).

EXPERT OPINION: Ultrasound techniques will stay as valuable tools for pleural effusions. Biomarkers in pleural fluid do not currently provide an acceptable yield for MPE. In subjects with past history of asbestos exposure, some serum or plasma markers (soluble mesothelin, fibulin) might help in selecting cases for close follow-up, to detect mesothelioma early. Needle pleural biopsy is justified only if used with image-techniques (ultrasound or CT) guidance, and thoracoscopy is better for both diagnosis and immediate palliative treatment (pleurodesis). Animal models of MPE and 'spheroids' are promising for research involving both pathophysiology and therapy. Considering the possibility of direct pleural delivery of nanotechnology-developed compounds-fit to both diagnosis and therapy purposes ('theranostics')-MPE and mesothelioma in particular are likely to benefit sooner than later from this exciting perspective.}, } @article {pmid23534732, year = {2013}, author = {Utkan, G and Ürün, Y and Cangir, AK and Kılıç, D and Özdemir, NY and Oztuna, DG and Bulut, E and Arslan, ÜY and Koçer, M and Kavukçu, Ş and İçli, F}, title = {Clinicopathological features of patients with malignant mesothelioma in a multicenter, case-control study: no role for ABO-Rh blood groups.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {14}, number = {1}, pages = {249-253}, pmid = {23534732}, issn = {2476-762X}, mesh = {ABO Blood-Group System/*blood ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Case-Control Studies ; Cisplatin/administration & dosage ; Confidence Intervals ; Deoxycytidine/administration & dosage/analogs & derivatives ; Female ; Glutamates/administration & dosage ; Guanine/administration & dosage/analogs & derivatives ; Humans ; Male ; Mesothelioma/*blood/*drug therapy/pathology ; Middle Aged ; Pemetrexed ; Retrospective Studies ; Rh-Hr Blood-Group System/*blood ; Turkey ; Gemcitabine ; }, abstract = {BACKGROUND: Malignant mesothelioma (MM) is an aggressive tumor of mesothelial surfaces. Previous studies have observed an association between ABO blood groups and risk of certain malignancies, including pancreatic and gastric cancer; however, no information on any association with MM risk is available. The aim of this study was to investigate possible associations amoong MM clinicopathological features and ABO blood groups and Rh factor.

MATERIALS AND METHODS: In 252 patients with MM, the ABO blood group and Rh factor were examined and compared with the control group of 3,022,883 healthy volunteer blood donors of Turkish Red Crescent between 2004 and 2011. The relationship of blood groups with various clinicopathological features were also evaluated in the patient group.

RESULTS: The median age was 55 (range: 27-86) and 61.5% of patients were male. While 82.8% of patients had a history of exposure to asbestos, 60.7% of patients had a smoking history. Epithelioid (65.1%) was the most common histology and 18.7% of patients had mixed histology. Overall, the ABO blood group distribution of the 252 patients with MM was comparable with the general population. The median overall survival (OS) was 14 months (95% confidence interval, 11.3-16.6 months). The median OS for A, B, AB, and O were 11, 15, 16, and 15 months respectively (p=0.396). First line chemotherapy was administered to 118 patients. The median OS of patients on pemetrexed or gemcitabine was longer than patient who was not administered chemotherapy [17 months (95%CI, 11.7-22.2) vs. 9 months (95%CI, 6.9-11.0); p<0.001].

CONCLUSIONS: The results of this study suggest that patients with MM can benefit from treatment with pemetrexed or gemcitabine in combination with cisplatin. We did not observe a statistically significant association between ABO blood group and risk of MM.}, } @article {pmid23532794, year = {2013}, author = {Adib, G and Labrèche, F and De Guire, L and Dion, C and Dufresne, A}, title = {Short, fine and WHO asbestos fibers in the lungs of quebec workers with an asbestos-related disease.}, journal = {American journal of industrial medicine}, volume = {56}, number = {9}, pages = {1001-1014}, doi = {10.1002/ajim.22180}, pmid = {23532794}, issn = {1097-0274}, mesh = {Aged ; Aged, 80 and over ; Air Pollutants, Occupational/adverse effects/analysis/*chemistry ; Asbestos/adverse effects/analysis/*chemistry ; Asbestosis/*etiology ; Female ; Humans ; Industry ; Lung Neoplasms/*chemically induced ; Male ; Mesothelioma/*chemically induced ; Middle Aged ; Mineral Fibers/adverse effects/analysis ; Occupational Exposure/*adverse effects/analysis ; Quebec ; }, abstract = {BACKGROUND: The possible role of short asbestos fibers in the development of asbestos-related diseases and availability of lung fiber burden data prompted this study on the relationships between fiber characteristics and asbestos-related diseases among compensated workers.

METHODS: Data collected between 1988 and 2007 for compensation purposes were used; lung asbestos fibers content of 123 Quebec workers are described according to socio-demographic characteristics, job histories and diseases (asbestosis, mesothelioma, lung cancer).

RESULTS: Most workers (85%) presented chrysotile fibers in their lungs, and respectively 76%, 64%, and 43% had tremolite, amosite, and crocidolite. Half of the total fibers were short, 30% were thin fibers and 20% corresponded to the World Health Organization definition of fibers (length ≥ 5 μm, diameter ≥ 0.2 and <3 μm). Chrysotile fibers were still observed in the lungs of workers 30 years or more after last exposure.

CONCLUSION: Our findings stress the relevance of considering several dimensional criteria to characterize health risks associated with asbestos inhalation.}, } @article {pmid23532723, year = {2013}, author = {Wu, WT and Lu, YH and Lin, YJ and Yang, YH and Shiue, HS and Hsu, JH and Li, CY and Yang, CY and Liou, SH and Wu, TN}, title = {Mortality among shipbreaking workers in Taiwan--a retrospective cohort study from 1985 to 2008.}, journal = {American journal of industrial medicine}, volume = {56}, number = {6}, pages = {701-708}, doi = {10.1002/ajim.22135}, pmid = {23532723}, issn = {1097-0274}, mesh = {Adult ; Age Distribution ; Asbestos/adverse effects ; *Cause of Death ; Cohort Studies ; Confidence Intervals ; Female ; Humans ; Incidence ; *Industry ; Lung Neoplasms/etiology/*mortality/physiopathology ; Male ; Middle Aged ; Occupational Diseases/etiology/*mortality/physiopathology ; Occupational Exposure/*adverse effects ; Retrospective Studies ; Risk Assessment ; Sex Distribution ; Survival Analysis ; Taiwan ; Young Adult ; }, abstract = {BACKGROUND: Shipbreaking workers are typically exposed to a wide range of hazardous chemicals. However, long-term follow-up studies of their mortality patterns are lacking. This study examined mortality among shipbreaking workers over a 24-year follow-up period.

METHODS: A total of 4,962 shipbreaking workers were recruited from the database of the Kaohsiung Shipbreaking Workers Union. The data were then linked to the Taiwan National Death Registry from 1985 to 2008. The mortality ratios-standardized for age and calendar years-(SMRs) for various causes of deaths were calculated with reference to the general population of Taiwan.

RESULTS: Among men workers, a statistically significant increased SMR was observed for all causes (SMR = 1.28), all cancers (SMR = 1.26; particularly noteworthy for lesions of oral and nasopharyngeal: SMR 2.03, liver: SMR 4.63, and lung: SMR 1.36), cirrhosis of the liver (SMR = 1.32), and accidents (SMR = 1.91). A statistically significant increase in mortality was observed for respiratory system cancer (SMR = 1.87) and lung cancer (SMR = 1.91) among workers with a longer duration of employment (≥7 years). The result also showed that among shipbreaking workers who were still alive, two people had mesothelioma and 10 people have asbestosis.

CONCLUSIONS: Those employed in shipbreaking industries experienced an increase in mortality from all causes. The increased SMR for lung cancer was probably related to asbestos, metals, and welding fume exposure.}, } @article {pmid23520887, year = {2013}, author = {De Zotti, R and Barbati, G and Negro, C}, title = {[Autopsy findings and pleural plaques in the Malignant Mesothelioma (MM) Regional Register of Friuli-Venezia-Giulia].}, journal = {La Medicina del lavoro}, volume = {104}, number = {1}, pages = {55-66}, pmid = {23520887}, issn = {0025-7818}, mesh = {Aged ; Algorithms ; Asbestos/*adverse effects ; Asbestosis/complications/diagnosis/epidemiology/*pathology ; Autopsy ; Female ; Humans ; Incidence ; Italy/epidemiology ; Logistic Models ; Male ; Mesothelioma/diagnosis/epidemiology/etiology/*pathology ; Middle Aged ; Pleura/*pathology ; Pleural Neoplasms/diagnosis/epidemiology/etiology/*pathology ; *Registries/statistics & numerical data ; }, abstract = {AIMS: To describe the cases of MM that occurred in the Friuli Venezia Giulia Region in the period 1995-2009 and evaluate the diagnostic contribution of autopsy findings.

METHODS: Via the Regional Register a search for MM cases was made following standardized criteria for diagnosis and past asbestos exposure assessment. Pleural plaques were identified by autopsy findings; the relationship between presence of pleural plaques and assessment of past asbestos exposure was analyzed.

RESULTS: 834 cases of MM were recorded and 458 autopsy findings were available; for 142 cases (15% of males and 23% of women) the first diagnosis was made at autopsy. Data were available on previous asbestos exposure in 91% (416 subjects) of cases with autopsy findings: 255 had "certain occupational exposure" (group 1), 116 "other occupational and non- occupational exposure" (group 2), 45 "negative and unknown exposure" (group 3). Logistic regression showed that significant predictors for pleural plaques were age at diagnosis (OR=1.03 each year (95% CI=1.01-1.05), asbestos exposure in group 1 versus group 2 (OR=6.8 (95% CI=4-12), and exposure in group 1 versus group 3 (OR=6.4 (95% CI=3-13). Among subjects in groups 1 and 2, the presence of pleural plagues was significantly associated with latency (OR=l.03 for each year of latency; 95% CI=1.01-1.22) and asbestos exposure in group 1 versus group 2 (OR=7.8; 95% CI=4.4-13.0).

CONCLUSIONS: Autopsy findings improved the diagnostic level of MM in elderly subjects, for whom reliable data on past asbestos exposure is often lacking. In subjects suffering from MM direct interview is always the best tool to evaluate past asbestos exposure; autopsy findings of pleural plaques cannot replace the anamnestic history when this is lacking, although such findings can act as a support.}, } @article {pmid23517112, year = {2013}, author = {Yuan, BZ and Chapman, J and Ding, M and Wang, J and Jiang, B and Rojanasakul, Y and Reynolds, SH}, title = {TRAIL and proteasome inhibitors combination induces a robust apoptosis in human malignant pleural mesothelioma cells through Mcl-1 and Akt protein cleavages.}, journal = {BMC cancer}, volume = {13}, number = {}, pages = {140}, pmid = {23517112}, issn = {1471-2407}, mesh = {Apoptosis/*drug effects ; Blotting, Western ; Cell Cycle/drug effects ; Cell Proliferation/drug effects ; Combined Modality Therapy ; Flow Cytometry ; Humans ; Lung Neoplasms/drug therapy/genetics/*pathology ; Mesothelioma/drug therapy/genetics/*pathology ; Mesothelioma, Malignant ; Myeloid Cell Leukemia Sequence 1 Protein/antagonists & inhibitors/genetics/*metabolism ; Pleural Neoplasms/drug therapy/genetics/*pathology ; Proteasome Inhibitors/*pharmacology ; Proto-Oncogene Proteins c-akt/genetics/*metabolism ; RNA, Messenger/genetics ; RNA, Small Interfering/genetics ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Tumor Cells, Cultured ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive malignancy closely associated with asbestos exposure and extremely resistant to current treatments. It exhibits a steady increase in incidence, thus necessitating an urgent development of effective new treatments.

METHODS: Proteasome inhibitors (PIs) and TNFα-Related Apoptosis Inducing Ligand (TRAIL), have emerged as promising new anti-MPM agents. To develop effective new treatments, the proapoptotic effects of PIs, MG132 or Bortezomib, and TRAIL were investigated in MPM cell lines NCI-H2052, NCI-H2452 and NCI-H28, which represent three major histological types of human MPM.

RESULTS: Treatment with 0.5-1 μM MG132 alone or 30 ng/mL Bortezomib alone induced a limited apoptosis in MPM cells associated with the elevated Mcl-1 protein level and hyperactive PI3K/Akt signaling. However, whereas 10-20 ng/ml TRAIL alone induced a limited apoptosis as well, TRAIL and PI combination triggered a robust apoptosis in all three MPM cell lines. The robust proapoptotic activity was found to be the consequence of a positive feedback mechanism-governed amplification of caspase activation and cleavage of both Mcl-1 and Akt proteins, and exhibited a relative selectivity in MPM cells than in non-tumorigenic Met-5A mesothelial cells.

CONCLUSION: The combinatorial treatment using TRAIL and PI may represent an effective new treatment for MPMs.}, } @article {pmid23516692, year = {2013}, author = {Reid, PA and Reid, PT}, title = {Occupational lung disease.}, journal = {The journal of the Royal College of Physicians of Edinburgh}, volume = {43}, number = {1}, pages = {44-48}, doi = {10.4997/JRCPE.2013.111}, pmid = {23516692}, issn = {2042-8189}, mesh = {Humans ; Lung Diseases/diagnosis/*etiology ; Occupational Diseases/*diagnosis ; Occupational Exposure/*adverse effects ; *Occupations ; }, abstract = {Occupational medicine represents the interface between work and health. As such, its breadth encompasses issues of clinical medicine, epidemiology, occupational hygiene, toxicology, ethics, and the law. The diagnosis of an occupational lung disease has implications not only for the health of the worker, but also in some circumstances for the health of colleagues and the employer. It is not surprising that many clinicians find this challenging. The aim of this paper is to provide a summary of common work-related lung disorders, and stress the importance of considering a patients' occupation when presented with a range of respiratory symptoms.}, } @article {pmid23510890, year = {2014}, author = {Nguyen, BD}, title = {PET/CT demonstration and monitoring of thoracic and abdominal wall mesothelioma.}, journal = {Clinical nuclear medicine}, volume = {39}, number = {1}, pages = {e106-9}, doi = {10.1097/RLU.0b013e3182867d38}, pmid = {23510890}, issn = {1536-0229}, mesh = {Abdominal Wall/*diagnostic imaging ; Aged ; Female ; Humans ; Lung Neoplasms/*diagnostic imaging ; Mesothelioma/*diagnostic imaging ; Mesothelioma, Malignant ; *Multimodal Imaging ; *Radiography, Thoracic ; Radionuclide Imaging ; *Tomography, X-Ray Computed ; }, abstract = {Mesothelioma is a malignancy arising from the embryonic coelomic mesodermal lining forming the pleura, peritoneum, pericardium, and tunica vaginalis. It is mostly induced by exposure to asbestos. The author presents a 77-year-old woman with an atypical manifestation of epithelioid mesothelioma, which does not follow the expected clinical characteristics of this disease mentioned above. In this case, PET/CT provides useful information concerning the extension of the lesions to thoracic and abdominal walls not fully evaluated by the initial conventional cross-sectional imaging. PET/CT also allows an accurate therapeutic monitoring of the disease.}, } @article {pmid23484611, year = {2013}, author = {Skammeritz, E and Omland, Ø and Hansen, J and Johansen, JP}, title = {Regional differences in incidence of malignant mesothelioma in Denmark.}, journal = {Danish medical journal}, volume = {60}, number = {3}, pages = {A4592}, pmid = {23484611}, issn = {2245-1919}, mesh = {Denmark ; Female ; Humans ; Incidence ; Kaplan-Meier Estimate ; Male ; Mesothelioma/*epidemiology ; *Pericardium ; Peritoneal Neoplasms/*epidemiology ; Pleural Neoplasms/*epidemiology ; Registries ; }, abstract = {INTRODUCTION: The incidence of malignant mesothelioma (MM) in Denmark has been rising rapidly since the 1950s. The aim of this study was to determine temporal developments of MM incidence and survival in Denmark as a whole and in the individual regions.

MATERIAL AND METHODS: Data from the Danish Cancer Registry were used. Cases of MM of the pleura, peritoneum and pericardium occurring in the 1943-2009 period were included. National and regional incidence rates were calculated, age-standardised and stratified by various variables. Survival was calculated using Kaplan Meier plot.

RESULTS: The total national incidence of MM for men has been rising throughout the period and reached its maximum of 1.76 in 2008-2009. For women, the incidence rate has remained relatively steady, with a maximum of 0.5 in 1973-1977. Since the late 1980s, the Region of Northern Jutland has had the highest male incidence rate. The difference in relative risk for men in the Region of Southern Denmark and the Region of Northern Jutland was 1.53 in 2008-2009, and the relative risk of developing MM in the Region of Northern Jutland for the entire period collectively compared with Denmark as a whole was 1.38. No notable regional difference exists for women. Survival has improved for both men and women, but remains poor with a median survival of 12.5 months for men and 13.3 months for women in 2008-2009.

CONCLUSION: The national MM incidence for men continues to increase, perhaps showing a slight tendency towards deceleration in the most recent decade. A clear long-term effect of the Danish asbestos ban has not yet occurred.

FUNDING: not relevant.

TRIAL REGISTRATION: not relevant.}, } @article {pmid23484132, year = {2013}, author = {Tada, Y and Shimada, H and Hiroshima, K and Tagawa, M}, title = {A potential therapeutic strategy for malignant mesothelioma with gene medicine.}, journal = {BioMed research international}, volume = {2013}, number = {}, pages = {572609}, pmid = {23484132}, issn = {2314-6141}, mesh = {*Adenoviridae ; Animals ; Asbestos/adverse effects ; Carcinogens/toxicity ; *Gene Expression ; Genetic Therapy ; *Genetic Vectors ; Humans ; Lung Neoplasms/genetics/pathology/*therapy ; Mesothelioma/genetics/pathology/*therapy ; Mesothelioma, Malignant ; Neoplasm Metastasis ; *Transgenes ; }, abstract = {Malignant mesothelioma, closely linked with occupational asbestos exposure, is relatively rare in the frequency, but the patient numbers are going to increase in the next few decades all over the world. The current treatment modalities are not effective in terms of the overall survival and the quality of life. Mesothelioma mainly develops in the thoracic cavity and infrequently metastasizes to extrapleural organs. A local treatment can thereby be beneficial to the patients, and gene therapy with an intrapleural administration of vectors is one of the potential therapeutics. Preclinical studies demonstrated the efficacy of gene medicine for mesothelioma, and clinical trials with adenovirus vectors showed the safety of an intrapleural injection and a possible involvement of antitumor immune responses. Nevertheless, low transduction efficiency remains the main hurdle that hinders further clinical applications. Moreover, rapid generation of antivector antibody also inhibits transgene expressions. In this paper, we review the current status of preclinical and clinical gene therapy for malignant mesothelioma and discuss potential clinical directions of gene medicine in terms of a combinatory use with anticancer agents and with immunotherapy.}, } @article {pmid23480683, year = {2012}, author = {Pinton, G and Manente, AG and Moro, L and Mutti, L}, title = {Circulating tumor cells as a diagnostic test for malignant pleural mesothelioma.}, journal = {Expert opinion on medical diagnostics}, volume = {6}, number = {3}, pages = {171-173}, doi = {10.1517/17530059.2012.676042}, pmid = {23480683}, issn = {1753-0067}, abstract = {The detection of circulating tumor cells (CTCs) may have important prognostic and therapeutic implications; therefore, we expect a broader range of tumor types in which CTC detection and count will routinely be conducted in the coming years. This article evaluates the application of CTC as a potentially useful diagnostic and prognostic test in malignant pleural mesothelioma (MMe). MMe is a rare but increasingly prevalent, highly aggressive asbestos exposure-related tumor. MMe develops after long time latency, is rarely diagnosed at early stages, is poorly sensitive to conventional treatments and presents a very short survival upon diagnosis. Pursuing research of CTC in MMe can represent a very important task for all the clinical and preclinical scientists working on blood biomarkers of this tumor. Possibly in combination with other diagnostic tools, such as a thoracoscopy and advanced imaging, CTC can represent a promising tool for MMe prognosis and follow-up. Further studies to confirm value of CTC test in MMe are warranted.}, } @article {pmid23471464, year = {2013}, author = {Lacourt, A and Gramond, C and Audignon, S and Ducamp, S and Févotte, J and Soit Ilg, AG and Goldberg, M and Imbernon, E and Brochard, P}, title = {Pleural mesothelioma and occupational coexposure to asbestos, mineral wool, and silica.}, journal = {American journal of respiratory and critical care medicine}, volume = {187}, number = {9}, pages = {977-982}, doi = {10.1164/rccm.201210-1911OC}, pmid = {23471464}, issn = {1535-4970}, mesh = {Aged ; Asbestos/*toxicity ; Calcium Compounds/*toxicity ; Case-Control Studies ; France ; Humans ; Logistic Models ; Male ; Mesothelioma/*chemically induced ; Middle Aged ; Occupational Diseases/chemically induced ; Occupational Exposure/*adverse effects ; Odds Ratio ; Pleural Neoplasms/*chemically induced ; Risk ; Silicates/*toxicity ; Silicon Dioxide/*toxicity ; }, abstract = {RATIONALE: Occupational coexposure to asbestos and other fibers or particles could modify the carcinogenicity of asbestos with regard to pleural mesothelioma.

OBJECTIVES: To estimate associations between pleural mesothelioma and occupational mineral wool and silica exposure and to study the impact of occupational coexposure on the risk of pleural mesothelioma.

METHODS: A total of 1,199 male cases and 2,379 control subjects were included in a French pooled case-control study. Complete job histories were collected, and occupational exposure to asbestos, mineral wool (MW), and silica were assessed by three French job exposure matrices. Unconditional logistic regression models adjusted for age, birth date, and occupational asbestos exposure were used to estimate odds ratios (OR) and 95% confidence intervals (CIs).

MEASUREMENTS AND MAIN RESULTS: A significant association between mesothelioma and MW exposure was observed after adjustment for occupational asbestos exposure. OR for subjects exposed to less than 0.01 fibers·ml(-1)·yr(-1) was 1.6 (95% CI, 1.2-2.1) and increased to 2.5 (95% CI, 1.8-3.4) for subjects exposed to more than 0.32 fibers·ml(-1)·yr(-1). All ORs for silica exposure were around the null. Coexposure to either asbestos and MW or asbestos and silica seemed to increase the risk of pleural mesothelioma. ORs were 17.6 (95% CI, 11.8-26.2) and 9.8 (95% CI, 4.2-23.2) for subjects exposed to both asbestos and MW and for subjects exposed to both asbestos and silica, respectively, compared with 4.3 (95% CI, 1.9-9.8) for occupational asbestos exposure alone.

CONCLUSIONS: Our results are in favor of an increased risk of pleural mesothelioma for subjects exposed to both asbestos and MW or asbestos and silica.}, } @article {pmid23470780, year = {2013}, author = {Kim, J and Oak, C and Jang, T and Jung, M and Chun, B and Park, EK and Takahashi, K}, title = {Lung cancer probably related to talc exposure: a case report.}, journal = {Industrial health}, volume = {51}, number = {2}, pages = {228-231}, doi = {10.2486/indhealth.ms1385}, pmid = {23470780}, issn = {1880-8026}, mesh = {Aged, 80 and over ; Asbestos/adverse effects ; Bronchoscopy ; Carcinoma, Squamous Cell/diagnosis/*etiology ; Fatal Outcome ; Humans ; Lung Neoplasms/diagnosis/*etiology ; Male ; Occupational Diseases/diagnosis/*etiology ; Occupational Exposure/*adverse effects ; Smoking/adverse effects ; Talc/*adverse effects ; Tomography, X-Ray Computed ; }, abstract = {Industrial talc has been widely circulated in the world for a long time. The pure talc has little effects on humans, but inhalation of talc contaminated with asbestos can causes severe asbestos-related diseases such as lung cancer and malignant mesothelioma. Herein, we represent a case of lung cancer after occupational exposure to industrial talc in the rubber manufacturing industry.}, } @article {pmid23463177, year = {2013}, author = {Nishimura, Y and Maeda, M and Kumagai-Takei, N and Lee, S and Matsuzaki, H and Wada, Y and Nishiike-Wada, T and Iguchi, H and Otsuki, T}, title = {Altered functions of alveolar macrophages and NK cells involved in asbestos-related diseases.}, journal = {Environmental health and preventive medicine}, volume = {18}, number = {3}, pages = {198-204}, pmid = {23463177}, issn = {1347-4715}, mesh = {Animals ; Asbestos/immunology/*toxicity ; Asbestosis/etiology/*immunology/pathology ; Cell Line ; Cytotoxicity, Immunologic/drug effects ; Environmental Pollutants/immunology/*toxicity ; Humans ; Killer Cells, Natural/*drug effects/immunology ; Lung Neoplasms/etiology/*immunology/pathology ; Macrophages, Alveolar/*drug effects/immunology ; Mesothelioma/etiology/*immunology/pathology ; Mesothelioma, Malignant ; Rats ; }, abstract = {Asbestos exposure causes asbestosis and malignant mesothelioma, disorders which remain difficult to cure. We focused on alveolar macrophages (AM) and natural killer (NK) cells in asbestosis and mesothelioma, respectively, and examined their functions upon exposure to asbestos or in patients with mesothelioma. Exposure to asbestos caused rat AM to exhibit high production of transforming growth factor-beta (TGF-β) with prolonged survival in the absence of other cells, not simultaneously with the apoptosis caused by asbestos. The NK cell line showed impaired cytotoxicity with altered expression of activating receptors upon exposure to asbestos, and primary NK cells in culture with asbestos and peripheral blood NK cells in mesothelioma shared a decrease in expression of NKp46, a representative activating receptor. The AM finding indicates that AM contribute to asbestosis by playing a direct role in the fibrogenic response, as well as the inflammatory response. The response of NK cells indicates that exposure to asbestos has an immune-suppressive effect, as well as a tumorigenic effect. Our studies therefore reveal novel effects of asbestos exposure on AM and tumor immunity, which may represent valuable information for construction of a strategy for prevention and cure of asbestosis and malignant mesothelioma.}, } @article {pmid23455802, year = {2012}, author = {Anirudhan, TN and Chakravarthy, R and Jothishankar, P}, title = {A unique case of well differentiated papillary mesothelioma involving an inguinal hernia.}, journal = {Indian journal of pathology & microbiology}, volume = {55}, number = {4}, pages = {546-548}, doi = {10.4103/0377-4929.107810}, pmid = {23455802}, issn = {0974-5130}, mesh = {Biomarkers, Tumor/analysis ; Hernia, Inguinal/*complications/*diagnosis/pathology/surgery ; Histocytochemistry ; Humans ; Immunohistochemistry ; Male ; Mesothelioma/*complications/*diagnosis/pathology/surgery ; Microscopy ; Middle Aged ; Peritoneal Neoplasms/*diagnosis/*pathology/surgery ; }, abstract = {Well Differentiated Papillary Mesothelioma (WDPM) is an uncommon tumor occurring predominantly in the peritoneum of young women with no history of asbestos exposure. In this report, we present a case of 48 year old male patient presenting with indirect inguinal hernia and incidental finding of a WDPM in the hernial sac during surgery. The unusual site of presentation and the relative rarity of this neoplasm in males evoke much clinico-pathological interest.}, } @article {pmid23450672, year = {2013}, author = {Finkelstein, MM}, title = {Pneumoconiosis and malignant mesothelioma in a family operated metal casting business that used industrial talc from New York state.}, journal = {American journal of industrial medicine}, volume = {56}, number = {5}, pages = {550-555}, doi = {10.1002/ajim.22159}, pmid = {23450672}, issn = {1097-0274}, mesh = {Aged ; Asbestos, Amphibole ; Asbestosis/diagnosis ; Fatal Outcome ; Female ; Humans ; Lung Neoplasms/*diagnosis/pathology ; Male ; Mesothelioma/*diagnosis/pathology ; Mesothelioma, Malignant ; Middle Aged ; New York ; Particle Size ; Pneumoconiosis/*diagnosis/pathology ; Talc/*adverse effects/analysis ; }, abstract = {BACKGROUND: The United States is second only to the People's Republic of China in annual talc production. U.S. talc is used in the production of ceramics, paint, paper, plastics, roofing, rubber, cosmetics, flooring, caulking, and agricultural applications. A number of U.S. talc deposits consistently contain talc intergrown with amphiboles such as tremolite and/or anthophyllite. It has long been recognized that miners and millers of talc deposits are at risk for pneumoconiosis and it has recently been reported that it is prudent, on the balance of probabilities, to conclude that dusts from New York State talc ores are capable of causing mesothelioma in exposed workers. This is a report of the diagnosis of pneumoconiosis and mesothelioma in a husband and wife who operated a small metal casting business that used industrial talc from New York as a parting agent.

METHODS: Case reports, including medical records and exposure histories, were provided by an attorney who had also commissioned laboratory investigation of the industrial talc product used in the factory.

RESULTS: Mrs X was diagnosed with pneumoconiosis characterized by interstitial fibrosis and heavily calcified pleural plaques. Mr X had calcified pleural plaques and developed a fatal pleural mesothelioma. Samples of the industrial talc contained fibrous tremolite and anthophyllite.

CONCLUSIONS: The author concludes that end users of industrial talc from New York State may be at risk of pneumoconiosis and malignant disease. End users of talcs from other regions of the United States, where talc formation arose from processes driven by regional metamorphism, might also be at risk.}, } @article {pmid23449737, year = {2013}, author = {Kumagai-Takei, N and Nishimura, Y and Maeda, M and Hayashi, H and Matsuzaki, H and Lee, S and Hiratsuka, J and Otsuki, T}, title = {Effect of asbestos exposure on differentiation of cytotoxic T lymphocytes in mixed lymphocyte reaction of human peripheral blood mononuclear cells.}, journal = {American journal of respiratory cell and molecular biology}, volume = {49}, number = {1}, pages = {28-36}, doi = {10.1165/rcmb.2012-0134OC}, pmid = {23449737}, issn = {1535-4989}, mesh = {Apoptosis ; Asbestos, Crocidolite/*adverse effects ; Asbestos, Serpentine/adverse effects ; Biomarkers/metabolism ; *Cell Differentiation ; Cell Proliferation ; Granzymes/metabolism ; Humans ; Interferon-gamma/metabolism ; Leukocytes, Mononuclear/*drug effects/immunology ; Lymphocyte Count ; *Lymphocyte Culture Test, Mixed ; T-Lymphocytes, Cytotoxic/*drug effects/immunology ; Tumor Necrosis Factor-alpha/metabolism ; }, abstract = {Asbestos fibers are associated with tumorigenicity, and are thought to cause mesothelioma. However, their effect on immune response remains unclear. We examined the effect of asbestos exposure on differentiation of cytotoxic T lymphocytes (CTLs) in mixed lymphocyte reactions (MLR) of human peripheral blood mononuclear cells (PBMCs) upon exposure to chrysotile B (CB) or crocidolite (CR) asbestos at 5 μg/ml for 7 days. Exposure to CB during MLR suppressed increases in the percentage and number of CD8[+] T cells in response to allogenic cells. The cytotoxicity for allogenic targets decreased in PBMCs exposed to CB, but not CR, when compared with PBMCs without any exposure during MLR. Exposure to CB during MLR resulted in suppression of increases in granzyme B[+] cells and IFN-γ[+] cells. CB exposure also resulted in suppression of increases in CD45RO[+] effector/memory cells and CD25[+]-activated cells in CD8[+] lymphocytes, and a decrease in CD45RA[+] cells. CB exposure suppressed the proliferation of CD8[+] lymphocytes without an increase in annexin V[+] apoptotic cells in CD8[+] lymphocytes. Moreover, the production of IL-10, IFN-γ, and TNF-α, but not IL-2, decreased in the presence of CB. These results suggest that exposure to asbestos potentially suppresses the differentiation of cytotoxic T lymphocyte, accompanied by decreases in IFN-γ and TNF-α.}, } @article {pmid23446998, year = {2013}, author = {Shukla, A and Miller, JM and Cason, C and Sayan, M and MacPherson, MB and Beuschel, SL and Hillegass, J and Vacek, PM and Pass, HI and Mossman, BT}, title = {Extracellular signal-regulated kinase 5: a potential therapeutic target for malignant mesotheliomas.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {19}, number = {8}, pages = {2071-2083}, pmid = {23446998}, issn = {1557-3265}, support = {R01 ES021110/ES/NIEHS NIH HHS/United States ; R01ES021110-02/ES/NIEHS NIH HHS/United States ; T32ESO77122//PHS HHS/United States ; }, mesh = {Animals ; Antineoplastic Agents/pharmacology ; Asbestos, Crocidolite/pharmacology ; Blotting, Western ; Cell Line, Tumor ; Cell Survival/drug effects/genetics ; Cisplatin/pharmacology ; Combined Modality Therapy ; Cytokines/genetics/metabolism ; Doxorubicin/pharmacology ; Enzyme Activation/drug effects ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Mesothelioma/*genetics/pathology/*therapy ; Mice ; Mice, SCID ; Mitogen-Activated Protein Kinase 7/*genetics/metabolism ; Oligonucleotide Array Sequence Analysis ; *RNA Interference ; Reverse Transcriptase Polymerase Chain Reaction ; Tumor Burden/drug effects/genetics ; Xenograft Model Antitumor Assays ; }, abstract = {PURPOSE: Malignant mesothelioma is a devastating disease with a need for new treatment strategies. In the present study, we showed the importance of extracellular signal-regulated kinase 5 (ERK5) in malignant mesothelioma tumor growth and treatment.

EXPERIMENTAL DESIGN: ERK5 as a target for malignant mesothelioma therapy was verified using mesothelial and mesothelioma cell lines as well as by xenograft severe combined immunodeficient (SCID) mouse models.

RESULTS: We first showed that crocidolite asbestos activated ERK5 in LP9 cells and mesothelioma cell lines exhibit constitutive activation of ERK5. Addition of doxorubicin resulted in further activation of ERK5 in malignant mesothelioma cells. ERK5 silencing increased doxorubicin-induced cell death and doxorubicin retention in malignant mesothelioma cells. In addition, shERK5 malignant mesothelioma lines exhibited both attenuated colony formation on soft agar and invasion of malignant mesothelioma cells in vitro that could be related to modulation of gene expression linked to cell proliferation, apoptosis, migration/invasion, and drug resistance as shown by microarray analysis. Most importantly, injection of shERK5 malignant mesothelioma cell lines into SCID mice showed significant reduction in tumor growth using both subcutaneous and intraperitoneal models. Assessment of selected human cytokine profiles in peritoneal lavage fluid from intraperitoneal shERK5 and control tumor-bearing mice showed that ERK5 was critical in regulation of various proinflammatory (RANTES/CCL5, MCP-1) and angiogenesis-related (interleukin-8, VEGF) cytokines. Finally, use of doxorubicin and cisplatin in combination with ERK5 inhibition showed further reduction in tumor weight and volume in the intraperitoneal model of tumor growth.

CONCLUSION: ERK5 inhibition in combination with chemotherapeutic drugs is a beneficial strategy for combination therapy in patients with malignant mesothelioma.}, } @article {pmid23442447, year = {2013}, author = {Croce, A and Musa, M and Allegrina, M and Trivero, P and Rinaudo, C}, title = {Environmental scanning electron microscopy technique to identify asbestos phases inside ferruginous bodies.}, journal = {Microscopy and microanalysis : the official journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada}, volume = {19}, number = {2}, pages = {420-424}, doi = {10.1017/S1431927612014390}, pmid = {23442447}, issn = {1435-8115}, mesh = {Air Pollutants, Occupational/analysis/toxicity ; Asbestos/*analysis/toxicity ; Humans ; Lung/chemistry/pathology/*ultrastructure ; Lung Neoplasms/*pathology ; Mesothelioma/*pathology ; Microscopy, Electron, Scanning/*methods ; Spectrometry, X-Ray Emission/*methods ; }, abstract = {Ferruginous bodies observed in lungs of patients affected by mesothelioma, asbestosis, and pulmonary carcinoma are important to relate the illness to exposure, environmental or occupational, to asbestos. Identification of the inorganic phase constituting the core of the ferruginous bodies, formed around asbestos but also around phases different from asbestos, is essential for legal purposes. Environmental scanning electron microscopy/energy dispersive spectroscopy was used to identify the fibrous mineral phase in the core of ferruginous bodies observed directly in thin sections of tissue, without digestion of the biological matrix. Spectra were taken with sequential analyses along a line crossing the core of the ferruginous bodies. By comparing the spectra taken near to and far from the core, the chemical elements that make up the core could be identified.}, } @article {pmid23435014, year = {2013}, author = {Andujar, P and Pairon, JC and Renier, A and Descatha, A and Hysi, I and Abd-Alsamad, I and Billon-Galland, MA and Blons, H and Clin, B and Danel, C and Debrosse, D and Galateau-Sallé, F and Housset, B and Laurent-Puig, P and Le Pimpec-Barthes, F and Letourneux, M and Monnet, I and Régnard, JF and Validire, P and Zucman-Rossi, J and Jaurand, MC and Jean, D}, title = {Differential mutation profiles and similar intronic TP53 polymorphisms in asbestos-related lung cancer and pleural mesothelioma.}, journal = {Mutagenesis}, volume = {28}, number = {3}, pages = {323-331}, doi = {10.1093/mutage/get008}, pmid = {23435014}, issn = {1464-3804}, mesh = {Aged ; Asbestos/*adverse effects ; Carcinoma, Non-Small-Cell Lung/chemically induced/genetics/pathology ; ErbB Receptors/genetics ; Female ; Humans ; *Introns ; Lung Neoplasms/chemically induced/*genetics/pathology ; Male ; Mesothelioma/chemically induced/*genetics/pathology ; Middle Aged ; *Mutation ; Neurofibromin 2/genetics ; Pleural Neoplasms/chemically induced/*genetics/pathology ; *Polymorphism, Genetic ; Proto-Oncogene Proteins/genetics ; Proto-Oncogene Proteins p21(ras) ; Smoking ; Tumor Suppressor Protein p53/*genetics ; ras Proteins/genetics ; }, abstract = {Given the interest in defining biomarkers of asbestos exposure and to provide insights into asbestos-related and cell-specific mechanisms of neoplasia, the identification of gene alterations in asbestos-related cancers can help to a better understanding of exposure risk. To understand the aetiology of asbestos-induced malignancies and to increase our knowledge of mesothelial carcinogenesis, we compared genetic alterations in relevant cancer genes between lung cancer, induced by asbestos and tobacco smoke, and malignant pleural mesothelioma (MPM), a cancer related to asbestos, but not to tobacco smoke. TP53, KRAS, EGFR and NF2 gene alteration analyses were performed in 100 non-small cell lung cancer (NSCLC) patients, 50 asbestos-exposed and 50 unexposed patients, matched for age, gender, histology and smoking habits. Detailed assessment of asbestos exposure was based on both specific questionnaires and asbestos body quantification in lung tissue. Genetic analyses were also performed in 34 MPM patients. TP53, EGFR and KRAS mutations were found in NSCLC with no link with asbestos exposure. NF2 was only altered in MPM. Significant enhancement of TP53 G:C to T:A transversions was found in NSCLC from asbestos-exposed patients when compared with unexposed patients (P = 0.037). Interestingly, TP53 polymorphisms in intron 7 (rs12947788 and rs12951053) were more frequently identified in asbestos-exposed NSCLC (P = 0.046) and MPM patients than in unexposed patients (P < 0.001 and P = 0.012, respectively). These results emphasise distinct genetic alterations between asbestos-related thoracic tumours, but identify common potential susceptibility factors, i.e. single nucleotide polymorphisms in intron 7 of TP53. While genetic changes in NSCLC are dominated by the effects of tobacco smoke, the increase of transversions in TP53 gene is consistent with a synergistic effect of asbestos. These results may help to define cell-dependent mechanisms of action of asbestos and identify susceptibility factors to asbestos.}, } @article {pmid23433295, year = {2012}, author = {Dahlgren, J and Peckham, T}, title = {Mesothelioma associated with use of drywall joint compound: a case series and review of literature.}, journal = {International journal of occupational and environmental health}, volume = {18}, number = {4}, pages = {337-343}, doi = {10.1179/2049396712Y.0000000009}, pmid = {23433295}, issn = {1077-3525}, mesh = {Air Pollutants/*toxicity ; Asbestos/*toxicity ; Construction Materials/*adverse effects ; Environmental Exposure/*adverse effects/statistics & numerical data ; Humans ; Mesothelioma/*chemically induced ; Microscopy, Phase-Contrast ; Respiratory Tract Neoplasms/*chemically induced ; }, abstract = {BACKGROUND: Drywall joint compound contained asbestos fibers, primarily chrysotile, in the 1950s through the 1970s. Workers in a variety of construction trades and homeowners were exposed to respirable asbestos from the use of these products, including during handling, mixing, sanding, and sweeping. Disturbance of in-place asbesto-containing joint compound continues to be a potential source of exposure during demolition or repair of wallboard. Studies from the 1970s and 1980s report air fiber measurements above current and historic regulatory limits during intended usage, and typical asbestos-related disease in drywall construction workers.

OBJECTIVES: We present three cases of mesothelioma in which the only known exposure to asbestos was from joint compound and review the literature on exposure circumstances, dose and fiber types.

CONCLUSIONS: Physicians treating mesothelioma patients should obtain a history of exposure to these products during work or home remodeling.}, } @article {pmid23433294, year = {2012}, author = {Freeman, MD and Kohles, SS}, title = {Assessing specific causation of mesothelioma following exposure to chrysotile asbestos-containing brake dust.}, journal = {International journal of occupational and environmental health}, volume = {18}, number = {4}, pages = {329-336}, doi = {10.1179/2049396712Y.0000000002}, pmid = {23433294}, issn = {1077-3525}, mesh = {Air Pollutants, Occupational/analysis/*toxicity ; Asbestos, Serpentine/analysis/*toxicity ; Automobiles ; Causality ; *Dust ; Humans ; Industry ; Mesothelioma/*chemically induced/epidemiology ; Occupational Exposure/adverse effects/statistics & numerical data ; Respiratory Tract Neoplasms/*chemically induced/epidemiology ; }, abstract = {BACKGROUND: The question of whether chrysotile asbestos-containing brake dust can plausibly serve as a cause of mesothelioma in an exposed individual has become a matter of heated debate in the medical literature despite multiple international, federal, and state governmental agencies acknowledging a causal association.

OBJECTIVES: We describe and provide an analysis of various industry and academic perspectives contributing to the debate.

METHODS: A framework is presented for evaluating the general and specific causal relationship between brake dust exposure and mesothelioma utilizing the principles of forensic epidemiology, and by applying the Bradford-Hill criteria.

RESULTS AND CONCLUSIONS: We conclude that there is a "net" of evidence favoring a causal relationship between brake dust-associated chrysotile exposure and mesothelioma. The industry-sponsored position that there is insufficient evidence to support a contiguous "chain" of causation is specious from both a methodologic and evidentiary perspective. Finally, we suggest a semiquantitative approach for the evaluation of individual causation in putative cases of mesothelioma with a history of significant brake dust exposure.}, } @article {pmid23433162, year = {2013}, author = {Zhang, H and Yu, WS and Li, GH}, title = {[One case report on malignant pleural mesothelioma by crocidolite].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {31}, number = {1}, pages = {56-57}, pmid = {23433162}, issn = {1001-9391}, mesh = {Asbestos, Crocidolite/*adverse effects ; Female ; Humans ; Mesothelioma/*etiology ; Middle Aged ; Pleural Neoplasms/*etiology ; }, } @article {pmid23433153, year = {2013}, author = {Huang, L and Dai, JM and Fu, H}, title = {[Comprehensive analysis of asbestos-induced occupational lung cancer and mesothelioma].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {31}, number = {1}, pages = {19-23}, pmid = {23433153}, issn = {1001-9391}, mesh = {Asbestos/*adverse effects ; Humans ; Lung Neoplasms/diagnosis/*etiology ; Mesothelioma/diagnosis/*etiology ; Occupational Diseases/diagnosis ; *Occupational Exposure ; Risk Assessment ; }, abstract = {OBJECTIVE: To revise diagnosis criteria of asbestos-induced occupational lung cancer.

METHODS: All literatures which met the criteria of cohort studies with results of lung cancer incidence or mortality among workers exposed to asbestos would incorporate into the systematic review. Meanwhile, the information about diagnosis criteria on asbestos-induced lung cancer in other countries was collected. Meta analysis was used to calculate meta-SMR and its 95% confidence interval.

RESULTS: 21 asbestos-exposed cohorts were summarized. The percentage of all deaths due to mesothelioma was 0 to 36.36%. The main kind of asbestos-exposed raw material was chrysotile which accounted for 47.6%, and 7 cohorts (33.3%) didn't provide the information. There were 13 cohorts in 15 which concluded that the lung cancer risk of workers with asbestos exposure had increased (lung cancer SMR = 1.6 ∼ 6.52, P < 0.05). Meta-SMR of 10 included cohorts is 2.09, with 95%CI 1.73 to 2.52 by using Meta analysis. When cumulative asbestos exposure years were less than one year, the risk of lung cancer had increased (lung cancer SMR = 1.6 ∼ 1.82, P < 0.05). When latent period of lung cancer was more than 15 years, the risk of lung cancer had increased (lung cancer SMR = 2.08 ∼ 3.75, P < 0.05). There were three studies, which had analyzed the relation between cumulative asbestos exposure years and the risk of mesothelioma, showing that when cumulative asbestos exposure years were less than one year, the risk of mesothelioma had increased (mesothelioma SMR = 18.0 ∼ 20.0, P < 0.05). When latent period of mesothelioma was more than 15 years, the risk of mesothelioma had increased.

CONCLUSION: The emphasis of the new version of asbestos-induced lung cancer and mesothelioma diagnosis criteria should focus on cumulative asbestos exposure years and latent period.}, } @article {pmid23432995, year = {2013}, author = {Satoh, M and Takemura, Y and Hamada, H and Sekido, Y and Kubota, S}, title = {EGCG induces human mesothelioma cell death by inducing reactive oxygen species and autophagy.}, journal = {Cancer cell international}, volume = {13}, number = {1}, pages = {19}, pmid = {23432995}, issn = {1475-2867}, abstract = {Malignant mesothelioma is an asbestos-related fatal disease with no effective cure. We studied whether a green tea polyphenol, epigallocathechin-3-gallate (EGCG), could induce cell death in five human mesothelioma cell lines. We found that EGCG induced apoptosis in all five mesothelioma cell lines in a dose-dependent manner. We further clarified the cell killing mechanism. EGCG induced reactive oxygen species (ROS), and impaired the mitochondrial membrane potential. As treatment with ROS scavengers, catalase and tempol, significantly inhibited the EGCG-induced apoptosis, ROS is considered to be responsible for the EGCG-induced apoptosis. Further, we found that EGCG induced autophagy, and that when autophagy was suppressed by chloroquine, the EGCG-induced cell death was enhanced. Taken together, these results suggest that EGCG has a great potential for the treatment of mesothelioma by inducing apoptosis and autophagy.}, } @article {pmid23423281, year = {2014}, author = {Felten, MK and Khatab, K and Knoll, L and Schettgen, T and Müller-Berndorff, H and Kraus, T}, title = {Changes of mesothelin and osteopontin levels over time in formerly asbestos-exposed power industry workers.}, journal = {International archives of occupational and environmental health}, volume = {87}, number = {2}, pages = {195-204}, pmid = {23423281}, issn = {1432-1246}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Aging/*blood ; Asbestos/*adverse effects ; Biomarkers, Tumor/*blood ; Case-Control Studies ; Early Detection of Cancer ; Female ; GPI-Linked Proteins/*blood ; Humans ; Longitudinal Studies ; Lung Neoplasms/*blood/diagnosis/etiology ; Male ; Mesothelin ; Mesothelioma/*blood/diagnosis/etiology ; Middle Aged ; Occupational Exposure/*adverse effects ; Osteopontin/*blood ; Pleural Neoplasms/*blood/diagnosis/etiology ; Power Plants ; Time Factors ; }, abstract = {PURPOSE: In patients developing malignant pleural mesothelioma (MPM) or lung cancer, using effective tumour markers is the quickest way to ensure early diagnosis and improve survival time. The aim of our study was to assess the influence of age and asbestos exposure on the blood levels of the proposed tumour markers, mesothelin and osteopontin, and to determine the change of these markers over time.

METHODS: We analysed 3,329 blood samples of 2,262 participants including 1,894 formerly asbestos-exposed power industry workers, a mixed group of 266 participants with an unknown history of asbestos exposure and a group of 102 non-asbestos-exposed controls. Marker concentrations were determined using commercial ELISA kits.

RESULTS: While age had a strong influence on marker levels, there was no association between exposure duration or benign asbestos-related disease and marker levels. In order to assess the maximum increase that can be expected to occur in asbestos-exposed workers those with an at least 10 % increase were selected (n = 290 for mesothelin and n = 81 for osteopontin). The 95th percentile of the annual change was 0.402 nmol/l for mesothelin and 334 ng/ml for osteopontin. In two patients with MPM and five with lung cancer, we could obtain more than one marker result before the diagnosis was made. Both MPM patients showed a steep increase of mesothelin levels.

CONCLUSIONS: Fixed cut-off values for deciding between intensive clinical work-up and continued surveillance appeared inadequate for the evaluated markers. While general conclusions cannot be drawn, we can say that the results of the two patients would be consistent with a mesothelin increase between 6 and 18 months before clinical symptoms developed.}, } @article {pmid23418337, year = {2013}, author = {Noguchi, K and Fujimoto, N and Asano, M and Fuchimoto, Y and Ono, K and Ozaki, S and Hotta, K and Kato, K and Toda, H and Taguchi, K and Kishimoto, T}, title = {Extrapulmonary small cell carcinoma mimicking malignant pleural mesothelioma.}, journal = {Journal of clinical pathology}, volume = {66}, number = {5}, pages = {450-451}, doi = {10.1136/jclinpath-2012-201401}, pmid = {23418337}, issn = {1472-4146}, mesh = {Aged, 80 and over ; Asbestos/adverse effects ; Autopsy ; Carcinoma, Small Cell/*secondary ; Carcinoma, Transitional Cell/*secondary ; Fatal Outcome ; Female ; Hepatitis C, Chronic/complications ; Humans ; Mesothelioma/*diagnosis ; Occupational Exposure/adverse effects ; Pleural Neoplasms/*diagnosis ; Smoking/adverse effects ; Urinary Bladder Neoplasms/*pathology ; }, } @article {pmid23415607, year = {2013}, author = {van der Bij, S and Baas, P and van de Vijver, MJ and de Mol, BA and Burgers, JA}, title = {Legal claims for malignant mesothelioma: dealing with all cases.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {80}, number = {2}, pages = {153-158}, doi = {10.1016/j.lungcan.2013.01.012}, pmid = {23415607}, issn = {1872-8332}, mesh = {Aged ; Asbestos/*toxicity ; Female ; Humans ; Lung Neoplasms/chemically induced/*diagnosis/pathology ; Male ; Mesothelioma/chemically induced/*diagnosis/pathology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Diseases/*diagnosis/pathology ; Occupational Exposure/*legislation & jurisprudence ; Workers' Compensation/legislation & jurisprudence ; }, abstract = {BACKGROUND: Apart of medical reasons, a definitive diagnosis of malignant mesothelioma may be required as a basis for a claim of financial compensation although a pathological source of conclusive evidence is missing. Clinical assessment of all available data is then the only option to come to a final conclusion. We evaluated the diagnostic work-up of a large cohort of Dutch patients who applied for financial compensation due to mesothelioma. We determined how often a pathological or clinical diagnosis can be made, and which factors are associated with making the final diagnosis malignant mesothelioma.

METHODS: A flow diagram of the diagnostic work-up was constructed for patients that applied to the Dutch institute for asbestos victims between 2005 and 2008 (N=1498). Both pathological and clinical factors that may influence the diagnostic outcome were assessed.

RESULTS: In 97 of the 1498 patients (6%) no pathologic diagnosis could be established because of an uncertain diagnosis (N=54), inadequate (N=22) or unavailable tumor samples (N=21). A final pathological diagnosis of malignant mesothelioma could most often be made when biopsy samples were available compared to those in whom only cytological material was available. In patients in who no conclusive diagnosis could be made, clinical assessment was performed. Eighty percent of patients (66/83) who were clinically assessed were considered to have mesothelioma. None of the clinical features analyzed were strongly associated with a confirmed diagnosis of malignant mesothelioma.

DISCUSSION: Our study shows that only in a small number of the patients who applied no pathologic diagnosis could be obtained. Based on judgment of clinical experts in the majority of these cases a near to certain diagnosis could be made. Moreover, it is reasonable to obtain biopsy material from patients to increase the chance to obtain a confirmed diagnosis. Therefore, it is important to refer patients early for diagnostic procedures.}, } @article {pmid23414396, year = {2013}, author = {Gauvin, H and Lacourt, A and Leffondré, K}, title = {On the proportional hazards model for occupational and environmental case-control analyses.}, journal = {BMC medical research methodology}, volume = {13}, number = {}, pages = {18}, pmid = {23414396}, issn = {1471-2288}, mesh = {Analysis of Variance ; *Asbestos ; Case-Control Studies ; Confidence Intervals ; *Environmental Exposure ; Humans ; Logistic Models ; Mesothelioma/*epidemiology ; *Occupational Exposure ; Proportional Hazards Models ; Risk Assessment ; }, abstract = {BACKGROUND: Case-control studies are generally designed to investigate the effect of exposures on the risk of a disease. Detailed information on past exposures is collected at the time of study. However, only the cumulated value of the exposure at the index date is usually used in logistic regression. A weighted Cox (WC) model has been proposed to estimate the effects of time-dependent exposures. The weights depend on the age conditional probabilities to develop the disease in the source population. While the WC model provided more accurate estimates of the effect of time-dependent covariates than standard logistic regression, the robust sandwich variance estimates were lower than the empirical variance, resulting in a low coverage probability of confidence intervals. The objectives of the present study were to investigate through simulations a new variance estimator and to compare the estimates from the WC model and standard logistic regression for estimating the effects of correlated temporal aspects of exposure with detailed information on exposure history.

METHOD: We proposed a new variance estimator using a superpopulation approach, and compared its accuracy to the robust sandwich variance estimator. The full exposure histories of source populations were generated and case-control studies were simulated within each source population. Different models with selected time-dependent aspects of exposure such as intensity, duration, and time since cessation were considered. The performances of the WC model using the two variance estimators were compared to standard logistic regression. The results of the different models were finally compared for estimating the effects of correlated aspects of occupational exposure to asbestos on the risk of mesothelioma, using population-based case-control data.

RESULTS: The superpopulation variance estimator provided better estimates than the robust sandwich variance estimator and the WC model provided accurate estimates of the effects of correlated aspects of temporal patterns of exposure.

CONCLUSION: The WC model with the superpopulation variance estimator provides an alternative analytical approach for estimating the effects of time-varying exposures with detailed history exposure information in case-control studies, especially if many subjects have time-varying exposure intensity over lifetime, and if only one control is available for each case.}, } @article {pmid23413596, year = {2012}, author = {Mineo, TC and Ambrogi, V}, title = {Malignant pleural mesothelioma: factors influencing the prognosis.}, journal = {Oncology (Williston Park, N.Y.)}, volume = {26}, number = {12}, pages = {1164-1175}, pmid = {23413596}, issn = {0890-9091}, mesh = {Biomarkers, Tumor/genetics/metabolism ; Biopsy ; Decision Support Techniques ; Diagnostic Imaging ; Gene Expression Regulation, Neoplastic ; Humans ; *Mesothelioma/genetics/metabolism/mortality/pathology/therapy ; Molecular Targeted Therapy ; Neoplasm Staging ; Patient Selection ; *Pleural Neoplasms/genetics/metabolism/mortality/pathology/therapy ; Predictive Value of Tests ; Prognosis ; Risk Factors ; }, abstract = {Malignant pleural mesothelioma (MPM) is a highly severe primary tumor of the pleura mainly related to exposure to asbestos fibers. The median survival after symptom onset is less than 12 months. Conventional medical and surgical therapies--either as single lines or combined--are not wholly effective. No universally accepted guidelines have yet been established for patient selection and the use of therapeutic strategies. In addition, retrospective staging systems have proved inadequate at improving therapeutic outcomes. Therapy is currently guided by gross tumor characteristics and patient features; however, these seem less accurate than the biological fingerprint of the tumor. A number of clinical prognostic factors have been considered in large multicenter series and independently validated. A series of novel biomarkers can predict the evolution of the disease. Here we summarize the principal and novel factors that influence prognosis and are thus potentially useful for selecting patients for targeted therapy.}, } @article {pmid23409888, year = {2013}, author = {Gibb, H and Fulcher, K and Nagarajan, S and McCord, S and Fallahian, NA and Hoffman, HJ and Haver, C and Tolmachev, S}, title = {Analyses of radiation and mesothelioma in the US Transuranium and Uranium Registries.}, journal = {American journal of public health}, volume = {103}, number = {4}, pages = {710-716}, pmid = {23409888}, issn = {1541-0048}, mesh = {Adult ; Aged ; Cause of Death ; Chi-Square Distribution ; Dose-Response Relationship, Radiation ; Female ; Humans ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; Middle Aged ; Neoplasms, Radiation-Induced/*mortality ; Occupational Diseases/*mortality ; Radiation Dosage ; Radiometry ; *Registries ; Risk Assessment ; Risk Factors ; United States/epidemiology ; *Uranium ; }, abstract = {OBJECTIVES: We examined the relationship between radiation and excess deaths from mesothelioma among deceased nuclear workers who were part of the US Transuranium and Uranium Registries.

METHODS: We performed univariate analysis with SAS Version 9.1 software. We conducted proportionate mortality ratio (PMR) and proportionate cancer mortality ratio (PCMR) analyses using the National Institute for Occupational Safety and Health Life Table Analysis System with the referent group being all deaths in the United States.

RESULTS: We found a PMR of 62.40 (P < .05) and a PCMR of 46.92 (P < .05) for mesothelioma. PMRs for the 4 cumulative external radiation dose quartiles were 61.83, 57.43, 74.46, and 83.31. PCMRs were 36.16, 47.07, 51.35, and 67.73. The PMR and PCMR for trachea, bronchus, and lung cancer were not significantly elevated.

CONCLUSIONS: The relationship between cumulative external radiation dose and the PMR and PCMR for mesothelioma suggests that external radiation at nuclear facilities is associated with an increased risk of mesothelioma. The lack of a significantly elevated PMR and PCMR for trachea, bronchus, and lung cancer suggests that asbestos did not confound this relationship.}, } @article {pmid23408016, year = {2013}, author = {Kao, SC and van Zandwijk, N and Corte, P and Clarke, C and Clarke, S and Vardy, J}, title = {Use of cancer therapy at the end of life in patients with malignant pleural mesothelioma.}, journal = {Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer}, volume = {21}, number = {7}, pages = {1879-1884}, pmid = {23408016}, issn = {1433-7339}, mesh = {Aged ; Australia ; Combined Modality Therapy ; Female ; Humans ; Lung Neoplasms/pathology/*therapy ; Male ; Mesothelioma/pathology/*therapy ; Mesothelioma, Malignant ; Middle Aged ; Palliative Care/*methods ; Pleural Neoplasms/pathology/*therapy ; Retrospective Studies ; Terminal Care/*methods ; Treatment Outcome ; }, abstract = {PURPOSE: Malignant pleural mesothelioma (MPM) is considered a treatment-resistant disease. We determined the proportion of patients who received treatment in the last month of life and potential factors associated with use of chemotherapy at the end of life.

METHODS: Consenting MPM patients compensated by the Dust Diseases Board (DDB) were included. Patient, treatment and outcome details were obtained through the DDB, treating physicians and Medicare Australia. The association between potential factors (age, gender, geographical location, disease stage, histological subtype, palliative care referral, length of first line chemotherapy and lines of treatment) and chemotherapy use in the last month of life was determined.

RESULTS: A total of 147 MPM patients were included in the analysis: 78 received chemotherapy, 50 had radiotherapy and 116 had surgery (77 received more than one treatment modality whilst 56 received one treatment modality). Twenty-one patients received treatment in their last month of life: nine received chemotherapy; six, radiotherapy and six had surgery. Those who were treated with second or subsequent lines of chemotherapy were more at risk of receiving chemotherapy until the end of life (six of 19 patients, i.e., 32 %) compared to those who were only treated with first-line therapy (three of 59 patients, i.e., 5 %; p < 0.01). Patients who received chemotherapy at the end of life had shorter survival compared to those who did not receive chemotherapy at the end of life (5.3 vs. 12.5 months, respectively; p = 0.01).

CONCLUSIONS: Chemotherapy utilisation in the last month of life is not uncommon in this series of MPM patients. Patients who failed previous chemotherapy were more likely to receive chemotherapy near the end of life. More careful consideration of when to cease chemotherapy needs to be made as patients who received chemotherapy at the end of life had poorer survival outcome.}, } @article {pmid23407863, year = {2012}, author = {Tamer Dogan, O and Salk, I and Tas, F and Epozturk, K and Gumus, C and Akkurt, I and Levent Ozsahin, S}, title = {Thoracic computed tomography findings in malignant mesothelioma.}, journal = {Iranian journal of radiology : a quarterly journal published by the Iranian Radiological Society}, volume = {9}, number = {4}, pages = {209-211}, pmid = {23407863}, issn = {1735-1065}, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is an uncommon neoplasm. MPM occurs more frequently in patients born or living in certain villages of Turkey.

OBJECTIVES: We aimed to review radiological findings of MPM.

PATIENTS AND METHODS: We reviewed the CT findings in 219 biopsy-proven MPM patients admitted to our clinic between 1993 and 2008.

RESULTS: The most common CT findings included pleural thickening (n=197, 90%) classified as diffuse (n=138, 63%), nodular (n=49, 22%) and mass-type (n=16, 7%). Pleural effusion was found in 173 patients (79%), involvement of the interlobar fissures in 159 (73%), mediastinal pleural involvement in 170 (78%), volume contraction in 142 (65%), mediastinal shift in 102 (47%) and mediastinal lymphadenopathy in 54 (25%).

CONCLUSION: MPM may present with diverse radiological features. Pleural thickening and pleural effusion were the most frequent radiological findings. Thoracic CT scans might be assessed more cautiously in patients with environmental exposure to asbestos.}, } @article {pmid23405729, year = {2012}, author = {Berra, A and Romano, C}, title = {[Latency: relevant element in the attribution, forecast, and prevention of occupational neoplasms].}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {34}, number = {3 Suppl}, pages = {608-611}, pmid = {23405729}, issn = {1592-7830}, mesh = {Humans ; *Neoplasms/epidemiology/etiology/prevention & control ; *Occupational Diseases/epidemiology/etiology/prevention & control ; }, abstract = {The knowledge on latencies of occupational cancers is relevant as far as causal diagnosis, epidemiologic forecast and primary and secondary prevention are concerned. Literature mainly shows highly non specific data on tumour latencies. The widest burden of available data on occupational cancers relates to mesothelioma due to asbestos exposure. Data covering different cancers are scanty. The present review of available data anyway allows to set some values that can serve as a reference, even though major limitations are to be considered. In particular, still unanswered questions deal with the leading role of either the cancerogenic power of agents, or of the dose, the organ susceptibility, the cell doubling time of specific neoplasms, the role of confundings. Due to the high dispersion of the latency values reported for single tumour types, it is still questionable if mean or median values can be deemed reliable.}, } @article {pmid23405722, year = {2012}, author = {Massaro, T and Dragonieri, S and Martina, GL and Baldassarre, A and Cassano, F and Musti, M}, title = {[Asbestos and agriculture: new perspectives of risk].}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {34}, number = {3 Suppl}, pages = {581-582}, pmid = {23405722}, issn = {1592-7830}, mesh = {*Agricultural Workers' Diseases/epidemiology/etiology ; *Agriculture ; Asbestos/*adverse effects ; Female ; Humans ; Male ; Risk Factors ; }, abstract = {The presence of ophiolites in areas of Basilicata, where there have been reports of mesothelioma in farmers, is known. This study evaluates the increased risk of exposure to tremolite in carrying out agricultural activities. Cases of mesothelioma occurred in farmers with unknown exposure to asbestos have been selected and assessed the employment in areas contaminated by tremolite. Personal samplings were conducted in a group of farmers employed in these areas and a group of subjects used in activities that do not involve contact with the ground. For the 5% of cases of mesothelioma in the lucan register emerged exposure to asbestos exclusively in farming activities in areas at tremolite risk. The analysis of the samples showed the presence of personal fibers of tremolite in 2/3 of the cases. In 60% there was an overcoming of the natural limit of 2 ff/l, with a peak up to 23.6 ff/l. The study shows that the risk of exposure to tremolite in agriculture is significantly higher than natural exposure.}, } @article {pmid23405719, year = {2012}, author = {Sturchio, E and Amadori, A and Businaro, J and Ficociello, B and Ferrazza, P and Colosio, C and Minoia, C}, title = {[Possible use of microRNAs as biomarkers for monitoring of workers exposed to asbestos].}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {34}, number = {3 Suppl}, pages = {571-573}, pmid = {23405719}, issn = {1592-7830}, mesh = {Asbestos/*adverse effects ; Biomarkers/analysis ; Environmental Monitoring/*methods ; Humans ; MicroRNAs/*analysis ; Occupational Exposure/*adverse effects ; }, abstract = {Exposure to asbestos is the predominant cause of pleural mesothelioma (PM). The PM is a tumor difficult to diagnose, chemoresistant, and with rising Incidence. The long latency periods and the lack of preventive and therapeutic strategies for the MP, suggest that asbestos will be a social and health issue in the near future. Therefore, this overview focuses on current knowledge of epigenetic alterations and on the key role of microRNAs, small RNAs that negatively regulate gene expression, as biomarkers in PM development. Dysregulated microRNA expression pattern is specific for different cancers, including MP. MicroRNA expression analysis is a promising tool for diagnosis, typing of MP than normal tissue and other lung tumors and monitoring of new therapies. However, a better knowledge of miRNA signatures in PM is still necessary to verify the contribution of specific miRNAs as diagnostic biomarkers, also compared to different asbestos forms, exposure and subject work history.}, } @article {pmid23405717, year = {2012}, author = {Foddis, R and Bonotti, A and Sderci, F and Pistelli, A and Pantani, E and Franzini, M and Paolicchi, A and Baggiani, A and Cristaudo, A}, title = {[Preliminary study to evaluate the meaning of GGT fractions analysis in a population of workers previously exposed to asbestos].}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {34}, number = {3 Suppl}, pages = {565-567}, pmid = {23405717}, issn = {1592-7830}, mesh = {Asbestosis/*blood ; Humans ; Male ; Middle Aged ; Occupational Diseases/*blood ; Occupational Exposure/*adverse effects ; gamma-Glutamyltransferase/*blood ; }, abstract = {The GGT enzyme, considered for years only as a marker of liver disease and alcohol abuse, has now revealed a risk of death for many causes. Through a molecular exclusion chromatography on FPLC system (Fast Protein Liquid Chromatography), it is possible to discriminate four fractions of GGT, defined according to the molecular weight: big-GGT, medium-GGT, small-GGT and free-GGT. The objective was to study the preventing meaning of GGT fractions for asbestos-related diseases. This study was conducted on 129 workers previously exposed to asbestos, 22 patients affected by Malignant Pleural Mesothelioma and 107 healthy workers. Our data demonstrated a statistical significant correlation between the fraction free-GGT with the presence of MPM, suggesting a possible role for this molecule as a biomarker for MPM diagnosis. However, being a preliminary study, further studies are warranted to confirm our results.}, } @article {pmid23405716, year = {2012}, author = {D'Anna, M and Galli, L and Antoniazzi, E and Fazioli, R and Lattarini, M and Firmi, AM and Valcarenghi, M and Bottazzi, R and Marconi, S and Livella, M and Rondina, MT and Patrini, G and Gioia, R and Locati, M and Rossi, C}, title = {[Trend of the asbestos related diseases mortality in workers of a company in the province Cremona which manufactured asbestos products].}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {34}, number = {3 Suppl}, pages = {561-564}, pmid = {23405716}, issn = {1592-7830}, mesh = {Asbestos/*adverse effects ; Asbestosis/*mortality ; Humans ; Italy/epidemiology ; Manufactured Materials/*adverse effects ; Occupational Diseases/*mortality ; }, abstract = {The study analyzes the trend of asbestos-related diseases and mortality in workers of a company in the province of Cremona which manufactured asbestos products. It is confirmed that the exposure to a high concentration of asbestos fibers (estimated to more than 20 fibers/cc) strictly correlates with the onset of pathologies from asbestos. In the studied population were found 19 cases of neoplastic diseases (12 mesotheliomas and 7 bronchopulmonary carcinomas). This figure, compared to the company working population, which over the years has been an average of 80 units, while not enabling to calculate an incidence rate due to the lack of reliable data on population, is indicative of a very significant cause-effect relationship since these are neoplastic diseases that can still arise. So it is necessary to continue the health monitoring of formerly exposed workers and appropriate to try to extend it to all workers of the asbestos compartment.}, } @article {pmid23405715, year = {2012}, author = {Graia, S and Scafa, F and Baiardi, P and Candura, SM}, title = {[Malignant mesothelioma: analysis of a hospital case series].}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {34}, number = {3 Suppl}, pages = {558-560}, pmid = {23405715}, issn = {1592-7830}, mesh = {Adult ; Aged ; Female ; Hospitalization ; Humans ; Male ; *Mesothelioma/surgery ; Middle Aged ; *Pleural Neoplasms/surgery ; }, abstract = {The 2000-2010 case record of our Institute includes 77 cases of malignant mesothelioma (MM) [67 pleural (40 males, 27 females; mean age 63.9 years), 9 peritoneal (7 males, 2 females; 67.9 years) and one testicular (38 year-old man)], often associated, with various degree of probability, to previous asbestos exposure (occupational or environmental). Twenty-four patients with pleural MM had undergone surgery (12 pleural decortication and 12 pneumonectomy), with median survival, respectively, of 14 +/- 4.33 (standard error) and 38 +/- 4.27 months, longer than that recorded without surgery (8 +/- 0.94 months). Four peritoneal cases underwent peritonectomy with hyperthermic intraoperative chemotherapy: one is still alive 20 months after diagnosis, the others died at 8, 18 and 36 months. The testicular case is still living 6 years after radical orchidectomy. In conclusion, due to past asbestos use, MM is often observed in the current clinical practice. Patients treated surgically present longer survivals.}, } @article {pmid23405712, year = {2012}, author = {Balletta, A and Bonifaci, G and Citro, A and Continisio, R and Di Palma, P and D'Angelo, R and Iacoviello, P}, title = {[Asbestos: fifty years of work exposure in Campania and other Italian regions through INAIL experience].}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {34}, number = {3 Suppl}, pages = {545-551}, pmid = {23405712}, issn = {1592-7830}, mesh = {Academies and Institutes ; Asbestos/*adverse effects ; Humans ; Italy ; Occupational Exposure/*adverse effects/*statistics & numerical data ; Time Factors ; }, abstract = {The aim of the work is to proceed to the recognition of asbestos phenomenon in Campania and in the other regions with emphasis on the incidence and development of several related diseases. Using data from first INAIL Annual Report on the progress of occupational diseases until 1999, and the data provided by the INAIL CSA regarding the last 12 years (2000 to 2011), the incidence is illustrated for two-year periods, from 2000 to 2011, for the total of diseases and separately for: asbestosis, mesotheliomas, lung cancer and non-cancerous pleural lesions. The total of diseases by region for the period 2000-2011 has been reported. The survey results show a gradual increase in the total asbestos related diseases (15,998) due to the mesotheliomas portion (5739) while the trend of lung cancer is stationary (2,287). Pleural plaques have a variable growth in the various regions during recent years. Some significant case studies from Campania are reported.}, } @article {pmid23405711, year = {2012}, author = {Baldassarre, A and Massaro, T and Dragonieri, S and Martina, GL and Musti, M}, title = {[A case report: an university professor suffering from malignant mesothelioma].}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {34}, number = {3 Suppl}, pages = {542-544}, pmid = {23405711}, issn = {1592-7830}, mesh = {Aged ; Humans ; Male ; *Mesothelioma/diagnosis ; *Pleural Neoplasms/diagnosis ; Universities ; }, abstract = {During the activities of the Apulia Regional Operative Center (COR Puglia), pertaining to the National Registry of Mesothelioma (ReNaM), there was reported a case of malignant mesothelioma occurred in a male of 66 years old. The case we bring to the attention is about an university professor of chemistry who, since the early '70s, has conducted several studies on the physico-chemical properties of some metals, particulary in the field of thermochemical treatments of superficial hardening of steel for greater wear resistance, using a laboratory with ovens and asbestos-containing materials and consumables. In 2011, after almost 40 years, the subject comes to the attention of the Apulia Regional Operative Center, with histologic and immunohistochemical diagnosis of epithelioid mesothelioma, after completing the diagnostic procedure in a thoracic surgery ward, for the assessment and treatment of a right pleural effusion revealed during health checks.}, } @article {pmid23403931, year = {2013}, author = {O'Hanlon, LH}, title = {Researchers explore possible link between mesothelioma and dust emissions in southern Nevada.}, journal = {Journal of the National Cancer Institute}, volume = {105}, number = {5}, pages = {312-314}, doi = {10.1093/jnci/djt033}, pmid = {23403931}, issn = {1460-2105}, mesh = {Age Factors ; Age of Onset ; Aluminum Silicates/adverse effects/chemistry ; Asbestos/adverse effects ; *Dust ; Environmental Exposure/*adverse effects ; Geology ; Heart Neoplasms/chemically induced/epidemiology ; Humans ; Mesothelioma/*chemically induced/*epidemiology/prevention & control ; *Minerals/adverse effects/chemistry ; Nevada/epidemiology ; Occupational Exposure/adverse effects ; Pericardium ; Peritoneal Neoplasms/chemically induced/epidemiology ; Pleural Neoplasms/chemically induced/epidemiology ; Sex Factors ; }, } @article {pmid23395095, year = {2013}, author = {Mossman, BT and Shukla, A and Heintz, NH and Verschraegen, CF and Thomas, A and Hassan, R}, title = {New insights into understanding the mechanisms, pathogenesis, and management of malignant mesotheliomas.}, journal = {The American journal of pathology}, volume = {182}, number = {4}, pages = {1065-1077}, pmid = {23395095}, issn = {1525-2191}, support = {R01 ES021110/ES/NIEHS NIH HHS/United States ; T32 ES007122/ES/NIEHS NIH HHS/United States ; /ImNIH/Intramural NIH HHS/United States ; P01 CA11407/CA/NCI NIH HHS/United States ; }, mesh = {Asbestos/adverse effects ; Epigenesis, Genetic ; Humans ; Immunotherapy ; Inflammation/pathology ; Mesothelioma/diagnosis/genetics/*pathology/*therapy ; Models, Biological ; }, abstract = {Malignant mesothelioma (MM) is a relatively rare but devastating tumor that is increasing worldwide. Yet, because of difficulties in early diagnosis and resistance to conventional therapies, MM remains a challenge for pathologists and clinicians to treat. In recent years, much has been revealed regarding the mechanisms of interactions of pathogenic fibers with mesothelial cells, crucial signaling pathways, and genetic and epigenetic events that may occur during the pathogenesis of these unusual, pleiomorphic tumors. These observations support a scenario whereby mesothelial cells undergo a series of chronic injury, inflammation, and proliferation in the long latency period of MM development that may be perpetuated by durable fibers, the tumor microenvironment, and inflammatory stimuli. One culprit in sustained inflammation is the activated inflammasome, a component of macrophages or mesothelial cells that leads to production of chemotactic, growth-promoting, and angiogenic cytokines. This information has been vital to designing novel therapeutic approaches for patients with MM that focus on immunotherapy, targeting growth factor receptors and pathways, overcoming resistance to apoptosis, and modifying epigenetic changes.}, } @article {pmid23375775, year = {2013}, author = {Yokohira, M and Nakano, Y and Yamakawa, K and Kishi, S and Ninomiya, F and Saoo, K and Imaida, K}, title = {Strain differences in pleural mesothelial cell reactions induced by potassium octatitanate fibers (TISMO) infused directly into the thoracic cavity.}, journal = {Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie}, volume = {65}, number = {6}, pages = {925-932}, doi = {10.1016/j.etp.2013.01.006}, pmid = {23375775}, issn = {1618-1433}, mesh = {Animals ; Body Weight/drug effects ; Epithelium/*drug effects/pathology ; Female ; Immunohistochemistry ; Infusion Pumps ; Kidney/*drug effects/pathology ; Liver/*drug effects/pathology ; Lung/*drug effects/pathology ; Mice ; Organ Size/drug effects ; Particle Size ; Pleural Cavity/*drug effects/pathology ; Species Specificity ; Titanium/chemistry/*toxicity ; }, abstract = {Although we have previously reported that the fiber-shaped TISMO, morphologically similar to asbestos, can induce a severe mesothelial reaction in A/J mice, it is important to clarify any strain differences. In the present study, female A/J, C3H/HeN, ICR and C57BL/6 mice were therefore employed as test strains. At the beginning of the experiment, all mice underwent a left thoracotomy and direct administration of 3mg of TISMO particles suspended in 0.2 ml saline into the left thorax. The experiment was terminated after 21 weeks and all groups were sacrificed and the mesothelium and main organs were examined histopathologically. To contribute to mechanistic analysis, iron staining with Berlin blue and Turnbull's blue, and immunostaining for calretinin were also performed. The present experiment demonstrated only minor strain differences in the degree of pleural reaction to TISMO. However, there was clear variation in the iron and lymphocyte accumulation in the pleura and in the liver. This difference in response to TISMO fibers in vivo is important information when considering the development of mesothelioma as an animal model and the extrapolation to human risk from such animal studies.}, } @article {pmid23364080, year = {2013}, author = {Ndlovu, N and Naude, Jt and Murray, J}, title = {Compensation for environmental asbestos-related diseases in South Africa: a neglected issue.}, journal = {Global health action}, volume = {6}, number = {}, pages = {19410}, pmid = {23364080}, issn = {1654-9880}, mesh = {Adult ; Asbestosis/*economics/epidemiology ; *Compensation and Redress/legislation & jurisprudence ; Environmental Exposure/*economics/legislation & jurisprudence/statistics & numerical data ; Female ; Humans ; Mesothelioma/economics/epidemiology/etiology ; Middle Aged ; Mining ; South Africa/epidemiology ; Young Adult ; }, abstract = {BACKGROUND: Environmentally acquired asbestos-related diseases (ARDs) are of concern globally. In South Africa, there is widespread contamination of the environment due to historical asbestos mining operations that were poorly regulated. Although the law makes provision for the compensation of occupationally acquired ARDs, compensation for environmentally acquired ARDs is only available through the Asbestos Relief Trust (ART) and Kgalagadi Relief Trust, both of which are administered by the ART. This study assessed ARDs and compensation outcomes of environmental claims submitted to the Trusts.

METHODS: The personal details, medical diagnoses, and exposure information of all environmental claims considered by the Trusts from their inception in 2003 to April 2010 were used to calculate the numbers and proportions of ARDs and compensation awards.

RESULTS: There were 146 environmental claimants of whom 35 (23.9%) had fibrotic pleural disease, 1 (0.7%) had lung cancer, and 77 (52.7%) had malignant mesothelioma. 53 (36.3%) claimants were compensated: 20 with fibrotic pleural disease and 33 with mesothelioma. Of the 93 (63.7%) claimants who were not compensated, 33 had no ARDs, 18 had fibrotic pleural disease, 1 had lung cancer, and 44 had mesothelioma. In addition to having ARDs, those that were compensated had qualifying domestic (33; 62.2%) or neighbourhood (20; 37.8%) exposures to asbestos. Most of the claimants who were not compensated had ARDs but their exposures did not meet the Trusts' exposure criteria.

CONCLUSIONS: This study demonstrates the environmental impact of asbestos mining on the burden of ARDs. Mesothelioma was the most common disease diagnosed, but most cases were not compensated. This highlights that there is little redress for individuals with environmentally acquired ARDs in South Africa. To stop this ARD epidemic, there is a need for the rehabilitation of abandoned asbestos mines and the environment. These issues may not be unique to South Africa as many countries continue to mine and use asbestos.}, } @article {pmid23361197, year = {2013}, author = {Wang, X and Courtice, MN and Lin, S}, title = {Mortality in chrysotile asbestos workers in China.}, journal = {Current opinion in pulmonary medicine}, volume = {19}, number = {2}, pages = {169-173}, doi = {10.1097/MCP.0b013e32835d6f56}, pmid = {23361197}, issn = {1531-6971}, mesh = {Asbestos, Serpentine/*adverse effects ; Asbestosis/etiology/*mortality ; China/epidemiology ; Humans ; Lung Neoplasms/etiology/*mortality ; Occupational Exposure/*adverse effects ; Risk Factors ; }, abstract = {PURPOSE OF REVIEW: China has been the world's top chrysotile asbestos consumer and producer. However, the national mortality rate for asbestos-related diseases, particularly from malignancies, is unknown. This review elaborates recent studies on cancer mortality and nonmalignant respiratory diseases in Chinese chrysotile asbestos workers.

RECENT FINDINGS: Studies conducted in asbestos products factory workers and miners have demonstrated strong associations between exposure to chrysotile and mortality rates for lung cancer and nonmalignant respiratory diseases. Mortality rates for lung cancer and nonmalignant respiratory diseases in both asbestos workers and miners are four and three times higher, respectively, than expected, which are greater than those seen in studies from western countries, likely a reflection of heavier exposures and less effective protection for workers. An increased risk of gastrointestinal cancer was also detected in chrysotile miners. There have been surprisingly few reported cases of mesothelioma, however, which could, at least partially, indicate a problem in diagnosis.

SUMMARY: Given the substantially increased death risks for lung cancer and nonmalignant respiratory diseases, urgent efforts must be made to implement occupational health and safety regulations and decrease workers' exposures to prevent a future heavier disease burden. Meanwhile, improvements in diagnostics and systematic recording of the incidence and mortality of asbestos-related diseases are needed.}, } @article {pmid23358691, year = {2013}, author = {Hmeljak, J and Erčulj, N and Dolžan, V and Pižem, J and Kern, I and Kovač, V and Cemažar, M and Cör, A}, title = {Is survivin expression prognostic or predictive in malignant pleural mesothelioma?.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {462}, number = {3}, pages = {315-321}, pmid = {23358691}, issn = {1432-2307}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Female ; Humans ; Immunohistochemistry ; Inhibitor of Apoptosis Proteins/analysis/*biosynthesis ; Male ; Mesothelioma/*metabolism/mortality ; Middle Aged ; Pleural Neoplasms/*metabolism/mortality ; Prognosis ; Proportional Hazards Models ; Survivin ; }, abstract = {Malignant pleural mesothelioma is an incurable cancer strongly associated with asbestos exposure and characterised by poor response to treatment. The inhibitor-of-apoptosis protein family member survivin is involved in apoptosis and proliferation and is expressed in cancer cells only. The aims of the present study were to elucidate whether survivin expression is associated with tumour cell apoptosis and proliferation and to assess the prognostic and predictive value of survivin expression in malignant pleural mesothelioma. Archival pleural mesothelioma tissue samples from 101 patients were immunohistochemically analysed for nuclear expression of survivin, for proliferation with the use of Ki-67 as marker and for apoptosis using active caspase-3 as a marker. Staining results and clinical data were included in a survival analysis. Survivin was highly expressed in tumour cell nuclei in all samples and this correlated positively with both apoptosis and proliferation, but did not have a significant prognostic value. We found significantly higher survivin expression in patients who responded to chemotherapy compared to patients with progressive disease. Survivin expression might contribute to treatment response prediction, but survivin expression in malignant pleural mesothelioma did not have prognostic significance.}, } @article {pmid23357461, year = {2013}, author = {Creaney, J and Dick, IM and Dare, H and Demelker, Y and Nowak, AK and Musk, AW and Robinson, BW}, title = {Does CA125 binding to mesothelin impact the detection of malignant mesothelioma?.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {80}, number = {1}, pages = {39-44}, doi = {10.1016/j.lungcan.2012.12.008}, pmid = {23357461}, issn = {1872-8332}, mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor/blood/*metabolism ; CA-125 Antigen/blood/*metabolism ; Enzyme-Linked Immunosorbent Assay ; Female ; GPI-Linked Proteins/blood/*metabolism ; Humans ; Male ; Mesothelin ; Mesothelioma/blood/diagnosis/*metabolism ; Middle Aged ; Pentetic Acid/pharmacology ; Protein Binding/drug effects ; Sensitivity and Specificity ; Sodium Dodecyl Sulfate/pharmacology ; }, abstract = {The biomarker mesothelin is a useful diagnostic tool in malignant mesothelioma (MM) patients. It has high specificity but a sensitivity of only 50%. As mesothelin binds CA125, and as CA125 is often elevated in MM, we asked whether this binding affected measurable mesothelin levels in a relevant clinical setting. Mesothelin and CA125 concentrations were measured in the serum of 41 patients with MM. An assay was developed to detect mesothelin bound to CA125. Mesothelin was demonstrated to be bound by CA125 in 9 of 41 MM patients. This binding could be broken by the addition of sodium dodecyl sulphate and diethylenetriaminepenta acetic acid (DTPA) to the samples, however this did not lead to any change in the mesothelin level measured. We therefore conclude that binding of mesothelin to CA125 does not alter the measurement of mesothelin for the detection of MM.}, } @article {pmid23355760, year = {2013}, author = {Pairon, JC and Laurent, F and Rinaldo, M and Clin, B and Andujar, P and Ameille, J and Brochard, P and Chammings, S and Ferretti, G and Galateau-Sallé, F and Gislard, A and Letourneux, M and Luc, A and Schorlé, E and Paris, C}, title = {Pleural plaques and the risk of pleural mesothelioma.}, journal = {Journal of the National Cancer Institute}, volume = {105}, number = {4}, pages = {293-301}, doi = {10.1093/jnci/djs513}, pmid = {23355760}, issn = {1460-2105}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; France/epidemiology ; Humans ; Incidence ; Male ; Mesothelioma/diagnostic imaging/*epidemiology/etiology ; Middle Aged ; Occupational Exposure/*adverse effects ; Odds Ratio ; Pleura/diagnostic imaging/*pathology ; Pleural Neoplasms/diagnostic imaging/*epidemiology/etiology ; Proportional Hazards Models ; Tomography, X-Ray Computed ; }, abstract = {BACKGROUND: The association between pleural plaques and pleural mesothelioma remains controversial. The present study was designed to examine the association between pleural plaques on computed tomography (CT) scan and the risk of pleural mesothelioma in a follow-up study of asbestos-exposed workers.

METHODS: Retired or unemployed workers previously occupationally exposed to asbestos were invited to participate in a screening program for asbestos-related diseases, including CT scan, organized between October 2003 and December 2005 in four regions in France. Randomized, independent, double reading of CT scans by a panel of seven chest radiologists focused on benign asbestos-related abnormalities. A 7-year follow-up study was conducted in the 5287 male subjects for whom chest CT scan was available. Annual determination of the number of subjects eligible for free medical care because of pleural mesothelioma was carried out. Diagnosis certification was obtained from the French mesothelioma panel of pathologists. Survival regression based on the Cox model was used to estimate the risk of pleural mesothelioma associated with pleural plaques, with age as the main time variable and time-varying exposure variables, namely duration of exposure, time since first exposure, and cumulative exposure index to asbestos. All statistical tests were two-sided.

RESULTS: A total of 17 incident cases of pleural mesothelioma were diagnosed. A statistically significant association was observed between mesothelioma and pleural plaques (unadjusted hazard ratio (HR) = 8.9, 95% confidence interval [CI] = 3.0 to 26.5; adjusted HR = 6.8, 95% CI = 2.2 to 21.4 after adjustment for time since first exposure and cumulative exposure index to asbestos).

CONCLUSION: The presence of pleural plaques may be an independent risk factor for pleural mesothelioma.}, } @article {pmid23355759, year = {2013}, author = {Kratzke, R}, title = {Detection of mesothioloma remains a conundrum.}, journal = {Journal of the National Cancer Institute}, volume = {105}, number = {4}, pages = {254-255}, doi = {10.1093/jnci/djs651}, pmid = {23355759}, issn = {1460-2105}, mesh = {Asbestos/*adverse effects ; Humans ; Male ; Mesothelioma/*epidemiology ; Occupational Exposure/*adverse effects ; Pleura/*pathology ; Pleural Neoplasms/*epidemiology ; }, } @article {pmid23354805, year = {2013}, author = {Özbudak, İH and Özbudak, Ö and Arslan, G and Erdoğan, A and Özbılım, G}, title = {Metachronous malignant mesothelioma and pulmonary adenocarcinoma.}, journal = {Turk patoloji dergisi}, volume = {29}, number = {1}, pages = {83-86}, doi = {10.5146/tjpath.2013.01156}, pmid = {23354805}, issn = {1309-5730}, mesh = {Adenocarcinoma/diagnosis/*epidemiology/surgery ; Asbestos/adverse effects ; Biopsy ; Comorbidity ; Humans ; Lung Neoplasms/chemically induced/diagnosis/*epidemiology/surgery ; Male ; Mesothelioma/chemically induced/diagnosis/*epidemiology ; Mesothelioma, Malignant ; Middle Aged ; Neoplasms, Second Primary/chemically induced/diagnosis/*epidemiology ; Pneumonectomy ; Tomography, X-Ray Computed ; }, abstract = {The prevalence of multiple primary malignant neoplasms in a single patient is reported in a wide variation. The co-existence of malignant mesothelioma and pulmonary carcinoma is a rare entity. Herein, we reported a 60-year-old man who was a retired employee and heavy smoker. He had a suspicious history of asbestos exposure. He complained of chest pain and computerized tomography revealed a mass in the lower lobe of left lung. The patient underwent a left lower lobectomy and was diagnosed as pulmonary adenocarcinoma. During follow-up two years after surgery, the patient complained of dyspnea and chest computerized tomography scan revealed right pleural effusion and diffuse pleural thickening. For the differential diagnosis, the patient underwent wedge biopsy from the right lower lobe and was diagnosed as epithelial diffuse malignant mesothelioma. The development of malignant pleural mesothelioma and lung carcinoma could be associated with asbestos exposure. However, a history of asbestos exposure is not required for the diagnosis. The influence of effective anticancer therapies that improve the survival rates and increase the population ages could be related to the occurrence of a second malignancy.}, } @article {pmid23353042, year = {2013}, author = {Kayatta, MO and Dineen, SP and Sica, G and Puskas, JD and Pickens, A}, title = {Primary pericardial mesothelioma in a 19-year-old presenting as pericarditis.}, journal = {The Annals of thoracic surgery}, volume = {96}, number = {2}, pages = {680-681}, doi = {10.1016/j.athoracsur.2013.01.035}, pmid = {23353042}, issn = {1552-6259}, mesh = {Heart Neoplasms/*complications/diagnosis ; Humans ; Male ; Mesothelioma/*complications/diagnosis ; Pericarditis/*etiology ; *Pericardium ; Young Adult ; }, abstract = {Primary pericardial mesothelioma is a rare clinical entity. The association between asbestos and pericardial mesothelioma has not been well established, partly due to the small number of reported patients. Treatment options are limited for this very aggressive cancer. Surgical resection in the form of pericardiectomy can be curative, but owing to the frequently late presentation, surgical intervention is usually palliative. Chemotherapy and radiotherapy have overall poor results. We present the case of a 19-year-old man who initially had symptoms of pericarditis. He died 1 year after initial presentation.}, } @article {pmid23350030, year = {2013}, author = {Pascolo, L and Gianoncelli, A and Schneider, G and Salomé, M and Schneider, M and Calligaro, C and Kiskinova, M and Melato, M and Rizzardi, C}, title = {The interaction of asbestos and iron in lung tissue revealed by synchrotron-based scanning X-ray microscopy.}, journal = {Scientific reports}, volume = {3}, number = {}, pages = {1123}, pmid = {23350030}, issn = {2045-2322}, mesh = {Aged ; Aged, 80 and over ; Asbestos/chemistry/*metabolism ; Asbestosis/metabolism/pathology ; Calcium/chemistry/metabolism ; Carcinogens/chemistry/*metabolism ; Female ; Ferritins/metabolism ; Humans ; Iron/chemistry/*metabolism ; Lung/*metabolism/pathology ; Magnesium/chemistry/metabolism ; Male ; Microscopy, Electron, Scanning ; Phosphorus/chemistry/metabolism ; X-Ray Absorption Spectroscopy ; }, abstract = {Asbestos is a potent carcinogen associated with malignant mesothelioma and lung cancer but its carcinogenic mechanisms are still poorly understood. Asbestos toxicity is ascribed to its particular physico-chemical characteristics, and one of them is the presence of and ability to adsorb iron, which may cause an alteration of iron homeostasis in the tissue. This observational study reports a combination of advanced synchrotron-based X-ray imaging and micro-spectroscopic methods that provide correlative morphological and chemical information for shedding light on iron mobilization features during asbestos permanence in lung tissue. The results show that the processes responsible for the unusual distribution of iron at different stages of interaction with the fibres also involve calcium, phosphorus and magnesium. It has been confirmed that the dominant iron form present in asbestos bodies is ferritin, while the concurrent presence of haematite suggests alteration of iron chemistry during asbestos body permanence.}, } @article {pmid23347351, year = {2013}, author = {Liu, G and Cheresh, P and Kamp, DW}, title = {Molecular basis of asbestos-induced lung disease.}, journal = {Annual review of pathology}, volume = {8}, number = {}, pages = {161-187}, pmid = {23347351}, issn = {1553-4014}, support = {I01 BX000786/BX/BLRD VA/United States ; R01 ES020357/ES/NIEHS NIH HHS/United States ; R01ES020357/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Apoptosis/drug effects ; Asbestos/chemistry/*poisoning/*toxicity ; Asbestosis/*etiology/genetics/metabolism/*pathology ; DNA Damage ; DNA, Mitochondrial/drug effects ; Humans ; Lung Diseases/*etiology/genetics/metabolism/*pathology ; Lung Neoplasms/etiology/genetics/metabolism/pathology ; Mesothelioma/etiology/genetics/metabolism/pathology ; Oxidative Stress/drug effects ; Reactive Oxygen Species/metabolism ; }, abstract = {Asbestos causes asbestosis and malignancies by molecular mechanisms that are not fully understood. The modes of action underlying asbestosis, lung cancer, and mesothelioma appear to differ depending on the fiber type, lung clearance, and genetics. After reviewing the key pathologic changes following asbestos exposure, we examine recently identified pathogenic pathways, with a focus on oxidative stress. Alveolar epithelial cell apoptosis, which is an important early event in asbestosis, is mediated by mitochondria- and p53-regulated death pathways and may be modulated by the endoplasmic reticulum. We review mitochondrial DNA (mtDNA)-damage and -repair mechanisms, focusing on 8-oxoguanine DNA glycosylase, as well as cross talk between reactive oxygen species production, mtDNA damage, p53, OGG1, and mitochondrial aconitase. These new insights into the molecular basis of asbestos-induced lung diseases may foster the development of novel therapeutic targets for managing degenerative diseases (e.g., asbestosis and idiopathic pulmonary fibrosis), tumors, and aging, for which effective management is lacking.}, } @article {pmid23346982, year = {2013}, author = {Bernstein, D and Dunnigan, J and Hesterberg, T and Brown, R and Velasco, JA and Barrera, R and Hoskins, J and Gibbs, A}, title = {Health risk of chrysotile revisited.}, journal = {Critical reviews in toxicology}, volume = {43}, number = {2}, pages = {154-183}, pmid = {23346982}, issn = {1547-6898}, mesh = {Asbestos, Amphibole/*adverse effects/pharmacokinetics ; Asbestos, Serpentine/*adverse effects/pharmacokinetics ; Asbestosis/*etiology/metabolism/pathology ; Dose-Response Relationship, Drug ; Humans ; Inhalation Exposure ; Lung/drug effects/metabolism ; Lung Neoplasms/epidemiology/etiology ; Macrophages/drug effects/metabolism/pathology ; Particle Size ; Pleural Neoplasms/epidemiology/etiology ; }, abstract = {This review provides a basis for substantiating both kinetically and pathologically the differences between chrysotile and amphibole asbestos. Chrysotile, which is rapidly attacked by the acid environment of the macrophage, falls apart in the lung into short fibers and particles, while the amphibole asbestos persist creating a response to the fibrous structure of this mineral. Inhalation toxicity studies of chrysotile at non-lung overload conditions demonstrate that the long (>20 µm) fibers are rapidly cleared from the lung, are not translocated to the pleural cavity and do not initiate fibrogenic response. In contrast, long amphibole asbestos fibers persist, are quickly (within 7 d) translocated to the pleural cavity and result in interstitial fibrosis and pleural inflammation. Quantitative reviews of epidemiological studies of mineral fibers have determined the potency of chrysotile and amphibole asbestos for causing lung cancer and mesothelioma in relation to fiber type and have also differentiated between these two minerals. These studies have been reviewed in light of the frequent use of amphibole asbestos. As with other respirable particulates, there is evidence that heavy and prolonged exposure to chrysotile can produce lung cancer. The importance of the present and other similar reviews is that the studies they report show that low exposures to chrysotile do not present a detectable risk to health. Since total dose over time decides the likelihood of disease occurrence and progression, they also suggest that the risk of an adverse outcome may be low with even high exposures experienced over a short duration.}, } @article {pmid23335100, year = {2013}, author = {Bertino, P and Panigada, M and Soprana, E and Bianchi, V and Bertilaccio, S and Sanvito, F and Rose, AH and Yang, H and Gaudino, G and Hoffmann, PR and Siccardi, A and Carbone, M}, title = {Fowlpox-based survivin vaccination for malignant mesothelioma therapy.}, journal = {International journal of cancer}, volume = {133}, number = {3}, pages = {612-623}, pmid = {23335100}, issn = {1097-0215}, support = {G12 MD007601/MD/NIMHD NIH HHS/United States ; R01 AI089999/AI/NIAID NIH HHS/United States ; R01AI089999/AI/NIAID NIH HHS/United States ; P01 CA114047/CA/NCI NIH HHS/United States ; P01CA114047/CA/NCI NIH HHS/United States ; P20GM103516/GM/NIGMS NIH HHS/United States ; R01 CA160715/CA/NCI NIH HHS/United States ; R01CA160715/CA/NCI NIH HHS/United States ; G12RR003061/RR/NCRR NIH HHS/United States ; R21 AT004844/AT/NCCIH NIH HHS/United States ; G12 RR003061/RR/NCRR NIH HHS/United States ; G12MD007601/MD/NIMHD NIH HHS/United States ; P20 GM103466/GM/NIGMS NIH HHS/United States ; P30 CA071789/CA/NCI NIH HHS/United States ; P20 GM103516/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; CD8-Positive T-Lymphocytes/immunology ; Cancer Vaccines/*immunology ; Cell Line, Tumor ; Female ; Fowlpox virus/genetics/immunology ; Humans ; Immunotherapy ; Inhibitor of Apoptosis Proteins/*genetics/*immunology ; Interferon-gamma/immunology ; *Lung Neoplasms/immunology/prevention & control/therapy ; Lymph Nodes/immunology ; *Mesothelioma/immunology/prevention & control/therapy ; Mesothelioma, Malignant ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Repressor Proteins/*genetics/*immunology ; Spleen/immunology ; Survivin ; Vaccination ; }, abstract = {Survivin protein is an attractive candidate for cancer immunotherapy since it is abundantly expressed in most common human cancers and mostly absent in normal adult tissues. Malignant mesothelioma (MM) is a deadly cancer associated with asbestos or erionite exposure for which no successful therapies are currently available. In this study, we evaluated the therapeutic efficacy of a novel survivin-based vaccine by subcutaneous or intraperitoneum injection of BALB/c mice with murine fiber-induced MM tumor cells followed by vaccination with recombinant Fowlpox virus replicons encoding survivin. Vaccination generated significant immune responses in both models, leading to delayed tumor growth and improved animal survival. Flow cytometry and immunofluorescence analyses of tumors from vaccinated mice showed CD8(+) T-cell infiltration, and real-time PCR demonstrated increased mRNA and protein levels of immunostimulatory cytokines. Analyses of survivin peptide-pulsed spleen and lymph node cells from vaccinated mice using ELISPOT and intracellular cytokine staining confirmed antigen-specific, interferon-γ-producing CD8(+) T-cell responses. In addition pentamer-based flow cytometry showed that vaccination generated survivin-specific CD8(+) T cells. Importantly, vaccination did not affect fertility or induce autoimmune abnormalities in mice. Our results demonstrate that vaccination with recombinant Fowlpox expressing survivin improves T-cell responses against aggressive MM tumors and may form the basis for promising clinical applications.}, } @article {pmid23335081, year = {2013}, author = {Nolan, RP and Gamble, JF and Gibbs, GW}, title = {Letter to the editor on commentary: malignant mesothelioma incidence among talc miners and millers in New York state by M M Finkelstein.}, journal = {American journal of industrial medicine}, volume = {56}, number = {9}, pages = {1116-1118}, doi = {10.1002/ajim.22161}, pmid = {23335081}, issn = {1097-0274}, mesh = {Asbestos/*toxicity ; Humans ; Male ; Mesothelioma/*epidemiology ; *Mining ; Occupational Diseases/*epidemiology ; Occupational Exposure/*adverse effects ; Talc/*toxicity ; }, } @article {pmid23333048, year = {2013}, author = {Delourme, J and Dhalluin, X and Cortot, AB and Lafitte, JJ and Scherpereel, A}, title = {[Malignant pleural mesothelioma: diagnosis and treatment].}, journal = {Revue de pneumologie clinique}, volume = {69}, number = {1}, pages = {26-35}, doi = {10.1016/j.pneumo.2012.12.003}, pmid = {23333048}, issn = {1776-2561}, mesh = {Antineoplastic Agents/therapeutic use ; Asbestos/*adverse effects ; Biopsy ; France/epidemiology ; Humans ; Mesothelioma/*diagnosis/epidemiology/etiology/*therapy ; Pleural Neoplasms/*diagnosis/epidemiology/etiology/*therapy ; Pneumonectomy ; Thoracoscopy ; Treatment Outcome ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor issued from the mesothelial surface of the pleural space. A previous exposure to asbestos is the main risk factor of mesothelioma. Clinical signs are most of the time late and unspecific. Chest CT-scan, a key imaging procedure, usually shows a (unilateral) pleurisy associated with pleural nodular thickening. PET-scan associated with CT-scan may help to differenciate MPM from pleural benign tumors but it is not recommended for the diagnosis of MPM, as well as chest resonance magnetic imaging and blood or pleural fluid biomarkers, including soluble mesothelin still under investigation. The diagnosis of MPM is based on histology using essentially immunohistochemistry on pleural biopsies best obtained by thoracoscopy. The treatment of MPM relies mostly on chemotherapy. Surgery, pleurectomy/decortication or extrapleural pneumonectomy, is not recommended outside a clinical trial, as well as adjuvant chest radiotherapy. Prophylactic irradiation of chest scars and drains, validated by the French guidelines in 2005, is however highly discussed at the international level. Finally, numerous research studies presently assess the value of targeted therapies and biomarkers in MPM, opening new perspectives in the management of this cancer.}, } @article {pmid23329519, year = {2013}, author = {Abakay, A and Abakay, O and Tanrikulu, AC and Sezgi, C and Sen, H and Kaya, H and Kucukoner, M and Kaplan, MA and Celik, Y and Senyigit, A}, title = {Effects of treatment regimens on survival in patients with malignant pleural mesothelioma.}, journal = {European review for medical and pharmacological sciences}, volume = {17}, number = {1}, pages = {19-24}, pmid = {23329519}, issn = {1128-3602}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Kaplan-Meier Estimate ; Logistic Models ; Male ; Mesothelioma/mortality/*therapy ; Middle Aged ; Pleural Neoplasms/mortality/*therapy ; Retrospective Studies ; }, abstract = {BACKGROUND AND OBJECTIVE: In this study, we aimed to investigate the factors affecting the survival of patients with malignant pleural mesothelioma (MPM) according to their treatment regimens, including best supportive care (BSC), chemotherapy, surgical group and multimodality (MM) therapy.

PATIENTS: A retrospective analysis was performed on clinical data and treatment outcomes of 400 patients registered in our hospital with MPM between January 1989 and April 2010.

RESULTS: Mean age (p < 0.001), presence of asbestos exposure (p = 0.0014), presence of smoking history (p < 0.001), Karnofsky performance status (p < 0.001), histological subtype (p = 0.034) and stage (p < 0.001) variables were found to be significantly different among the four treatment regimens. Mean survival time of all patients was 12.32 months. Mean survival time 10.5 months for the BSC group, 15.7 for the surgical group, 16.02 for the chemotherapy group, and 26.55 for the MM group. There were significant differences in mean survival time among the four treatment regimens. In addition, a significant difference was found in survival time between the two chemotherapy groups (p = 0.032). Mean survival time for cisplatin + gemcitabine was found to be 14.49 months and for cisplatin + pemetrexed, 18.34 months.

CONCLUSIONS: The MM group had better survival rates than the other groups. The new chemotherapy combination, cisplatin + pemetrexed, can be helpful in improving survival time.      }, } @article {pmid23319692, year = {2013}, author = {Szlosarek, PW and Luong, P and Phillips, MM and Baccarini, M and Stephen, E and Szyszko, T and Sheaff, MT and Avril, N}, title = {Metabolic response to pegylated arginine deiminase in mesothelioma with promoter methylation of argininosuccinate synthetase.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {31}, number = {7}, pages = {e111-3}, doi = {10.1200/JCO.2012.42.1784}, pmid = {23319692}, issn = {1527-7755}, support = {7740/CRUK_/Cancer Research UK/United Kingdom ; G1001993/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Argininosuccinate Synthase/deficiency/genetics/*metabolism ; Asbestos/adverse effects ; Cisplatin/administration & dosage ; Clinical Trials as Topic ; *DNA Methylation ; Fatal Outcome ; *Fluorodeoxyglucose F18 ; Glutamates/administration & dosage ; Guanine/administration & dosage/analogs & derivatives ; Humans ; Hydrolases/*therapeutic use ; Male ; Mesothelioma/complications/diagnostic imaging/*drug therapy/*enzymology/etiology ; Middle Aged ; Mutation ; Occupational Exposure/adverse effects ; Pemetrexed ; Pleural Effusion, Malignant/etiology ; Pleural Neoplasms/complications/diagnostic imaging/*drug therapy/*enzymology/etiology ; Polyethylene Glycols/*therapeutic use ; Positron-Emission Tomography/*methods ; *Promoter Regions, Genetic ; Radiopharmaceuticals ; }, } @article {pmid23317248, year = {2012}, author = {Berk, S and Dogan, OT and Kilickap, S and Epozturk, K and Akkurt, I and Seyfikli, Z}, title = {Clinical characteristics, treatment and survival outcomes in malignant mesothelioma: eighteen years' experience in Turkey.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {13}, number = {11}, pages = {5735-5739}, doi = {10.7314/apjcp.2012.13.11.5735}, pmid = {23317248}, issn = {2476-762X}, mesh = {Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Female ; Follow-Up Studies ; Humans ; Male ; Mesothelioma/drug therapy/*mortality/pathology ; Middle Aged ; Neoplasm Staging ; Organoplatinum Compounds/administration & dosage ; Palliative Care ; Pleural Neoplasms/drug therapy/*mortality/pathology ; Prognosis ; Survival Rate ; Turkey ; Young Adult ; }, abstract = {BACKGROUND: Malignant mesothelioma (MM) is an insidious tumor with poor prognosis, arising from mesothelial surfaces such as pleura, peritoneum and pericardium. We here aimed to evaluate the demographic, clinical, and radiological features of patients with MM followed in our center as well as their survival.

METHODS: The study included 228 patients (131 male, 97 female) who were followed up in our institution between 1993 and 2010 with the diagnosis of MM.

RESULTS: The mean age was 59.1 years in men and 58.7 years in women and the sex ratio was 1.4:1 in favor of males. Environmental asbestos exposure was present in 86% of the patients for a mean duration of 40±20 years (range: 3-70). Pleural effusion and thoracic/abdominal pain were the most common presenting signs and symptoms (70.2% and 57.8%, respectively). One hundred-thirteen (66%) patients were treated with platinum-based combination chemotherapy (PBCT) plus supportive care (SC) and 67 (34%) patients received SC alone. The median follow-up time was 10.0 months. The median overall survival was significantly improved with PBCT plus SC compared to SC alone (11.4 vs. 5.1 months; p=0.005). The 6, 12, 18, and 24-month survival rates were significantly improved with PBCT plus SC compared to SC alone (72%, 43%, 19%, and 2% vs. 49%, 31%, 11%, and 1%).

CONCLUSION: The survival of patients with MM improved in patients treated with PBCT. The survival advantage continued 12- and 24-month after the initial time of combination chemotherapy.}, } @article {pmid23313295, year = {2013}, author = {Jagirdar, R and Solenov, EI and Hatzoglou, C and Molyvdas, PA and Gourgoulianis, KI and Zarogiannis, SG}, title = {Gene expression profile of aquaporin 1 and associated interactors in malignant pleural mesothelioma.}, journal = {Gene}, volume = {517}, number = {1}, pages = {99-105}, doi = {10.1016/j.gene.2012.12.075}, pmid = {23313295}, issn = {1879-0038}, mesh = {Aquaporin 1/*genetics ; Biomarkers, Tumor/*genetics ; *Computational Biology ; Data Mining ; *Gene Expression Profiling ; Humans ; Mesothelioma/classification/*genetics ; Oligonucleotide Array Sequence Analysis ; Pleural Neoplasms/classification/*genetics ; }, abstract = {Overexpression of AQP1 has recently been shown to be an independent prognostic factor in pleural mesothelioma favoring survival. This paper presents a data mining and bioinformatics approach towards the evaluation of the gene expression profile of AQP1 in malignant pleural mesothelioma and of AQP1 associated markers in the context of mesothelioma disease phenotype, CDKN2A gene deletion, sex and asbestos exposure. The data generated were thus again subjected to differential expression profile analysis. Here we report that AQP1 is overexpressed in epithelioid mesothelioma and identify TRIP6 and EFEMP2 as candidate genes for further investigation in mesothelioma.}, } @article {pmid23301745, year = {2013}, author = {Lamote, K and Baas, P and van Meerbeeck, JP}, title = {Fibulin-3 as a biomarker for pleural mesothelioma.}, journal = {The New England journal of medicine}, volume = {368}, number = {2}, pages = {189-190}, doi = {10.1056/NEJMc1213514}, pmid = {23301745}, issn = {1533-4406}, mesh = {*Asbestos ; Extracellular Matrix Proteins/*blood ; Female ; Humans ; Male ; Mesothelioma/*diagnosis ; *Occupational Exposure ; Pleural Neoplasms/*diagnosis ; }, } @article {pmid23301744, year = {2013}, author = {Hollevoet, K and Sharon, E}, title = {Fibulin-3 as a biomarker for pleural mesothelioma.}, journal = {The New England journal of medicine}, volume = {368}, number = {2}, pages = {189}, doi = {10.1056/NEJMc1213514}, pmid = {23301744}, issn = {1533-4406}, mesh = {*Asbestos ; Extracellular Matrix Proteins/*blood ; Female ; Humans ; Male ; Mesothelioma/*diagnosis ; *Occupational Exposure ; Pleural Neoplasms/*diagnosis ; }, } @article {pmid23301743, year = {2013}, author = {Pass, HI and Goparaju, C}, title = {Fibulin-3 as a biomarker for pleural mesothelioma.}, journal = {The New England journal of medicine}, volume = {368}, number = {2}, pages = {190}, pmid = {23301743}, issn = {1533-4406}, support = {U01 CA111295/CA/NCI NIH HHS/United States ; }, mesh = {*Asbestos ; Extracellular Matrix Proteins/*blood ; Female ; Humans ; Male ; Mesothelioma/*diagnosis ; *Occupational Exposure ; Pleural Neoplasms/*diagnosis ; }, } @article {pmid23301673, year = {2013}, author = {Pinton, G and Manente, AG and Murer, B and De Marino, E and Mutti, L and Moro, L}, title = {PARP1 inhibition affects pleural mesothelioma cell viability and uncouples AKT/mTOR axis via SIRT1.}, journal = {Journal of cellular and molecular medicine}, volume = {17}, number = {2}, pages = {233-241}, pmid = {23301673}, issn = {1582-4934}, mesh = {Acetylation ; Adult ; Aged ; Aged, 80 and over ; *Apoptosis ; Blotting, Western ; Cell Cycle ; *Cell Proliferation ; Female ; Humans ; Immunoenzyme Techniques ; Immunoprecipitation ; Male ; Mesothelioma/metabolism/mortality/*pathology ; Middle Aged ; Phosphorylation/drug effects ; Poly (ADP-Ribose) Polymerase-1 ; *Poly(ADP-ribose) Polymerase Inhibitors ; Poly(ADP-ribose) Polymerases/metabolism ; Prognosis ; Proto-Oncogene Proteins c-akt/*metabolism ; Sirtuin 1/*metabolism ; Survival Rate ; TOR Serine-Threonine Kinases/*metabolism ; }, abstract = {Malignant Pleural Mesothelioma (MMe) is a rare but increasingly prevalent, highly aggressive cancer with poor prognosis. The aetiology of MMe is essentially a function of previous exposure to asbestos fibres, which are considered to be an early-stage carcinogen. Asbestos is toxic to human mesothelial cells (HMCs), that activate the nuclear enzyme poly(ADP-ribose) polymerase-1 (PARP1) to repair DNA. The targeting of PARP1 is showing considerable potential for delivering selective tumour cell kill while sparing normal cells, and offers a scientifically rational clinical application. We investigated PARP1 expression in normal mesothelial and MMe tissues samples. Immunohistochemical analysis revealed low PARP1 staining in peritumoural mesothelium. As opposite, a progressive increase in epithelioid and in the most aggressive sarcomatoid MMe tissues was evident. In MMe cell lines, we correlated increased PARP1 expression to sensitivity to its inhibitor CO-338 and demonstrated that CO-338 significantly reduced cell viability as single agent and was synergistic with cis-platin. Interestingly, we described a new correlation between PARP1 and the AKT/mTOR axis regulated by SIRT1. SIRT1 has a role in the modulation of AKT activation and PARP1 has been described to be a gatekeeper for SIRT1 activity by limiting NAD+ availability. Here, we firstly demonstrate an inverse correlation between AKT acetylation and phosphorylation modulated by SIRT1 in MMe cells treated with CO-338. In conclusion, this study demonstrates that PARP1 overexpression defines increased responsiveness to its inhibition, then these results imply that a substantial fraction of patients could be candidates for therapy with PARP inhibitors.}, } @article {pmid23297667, year = {2013}, author = {Stayner, L and Welch, LS and Lemen, R}, title = {The worldwide pandemic of asbestos-related diseases.}, journal = {Annual review of public health}, volume = {34}, number = {}, pages = {205-216}, doi = {10.1146/annurev-publhealth-031811-124704}, pmid = {23297667}, issn = {1545-2093}, mesh = {Asbestos/*adverse effects ; Asbestosis/*epidemiology/etiology/mortality ; Developed Countries/statistics & numerical data ; Developing Countries/statistics & numerical data ; Humans ; Lung Neoplasms/*epidemiology/etiology/mortality ; Mesothelioma/*epidemiology/etiology/mortality ; Occupational Exposure/adverse effects/*statistics & numerical data ; *Pandemics ; World Health Organization ; }, abstract = {Asbestos-related diseases are still a major public health problem. The World Health Organization (WHO) has estimated that 107,000 people worldwide die each year from mesothelioma, lung cancer, and asbestosis. We review what is known about asbestos use, production, and exposure and asbestos-related diseases in the world today, and we offer predictions for the future. Although worldwide consumption of asbestos has decreased, consumption is increasing in many developing countries. The limited data available suggest that exposures may also be high in developing countries. Mesothelioma is still increasing in most European countries and in Japan but has peaked in the United States and Sweden. Although the epidemic of asbestos-related disease has plateaued or is expected to plateau in most of the developed world, little is known about the epidemic in developing countries. It is obvious that increased asbestos use by these countries will result in an increase in asbestos-related diseases in the future.}, } @article {pmid23293508, year = {2012}, author = {Rosario, CM and Lin, X and Kamp, DW}, title = {Mesothelioma - Update on Diagnostic Strategies.}, journal = {Clinical pulmonary medicine}, volume = {19}, number = {6}, pages = {282-288}, pmid = {23293508}, issn = {1068-0640}, support = {I01 BX000786/BX/BLRD VA/United States ; R01 ES020357/ES/NIEHS NIH HHS/United States ; }, abstract = {Malignant pleural mesothelioma (MPM) can be a challenging diagnosis for clinicians to make as it is often difficult to distinguish from benign asbestos pleural effusions and metastatic carcinomas. In this review, we present a case of MPM and discuss clinical manifestations, traditional diagnostic techniques, and the role of cytopathologic immunostains and serum biomarkers in the diagnosis of MPM.}, } @article {pmid23277285, year = {2013}, author = {Filiberti, R and Marroni, P and Mencoboni, M and Mortara, V and Caruso, P and Cioè, A and Michelazzi, L and Merlo, DF and Bruzzone, A and Bobbio, B and Del Corso, L and Galli, R and Taveggia, P and Dini, G and Spigno, F}, title = {Individual predictors of increased serum mesothelin in asbestos-exposed workers.}, journal = {Medical oncology (Northwood, London, England)}, volume = {30}, number = {1}, pages = {422}, pmid = {23277285}, issn = {1559-131X}, mesh = {Aged ; Asbestos/adverse effects ; Biomarkers, Tumor/*blood ; Early Detection of Cancer/*methods ; Enzyme-Linked Immunosorbent Assay ; GPI-Linked Proteins/*blood ; Humans ; Male ; Mesothelin ; Mesothelioma/blood/*diagnosis ; Middle Aged ; Occupational Exposure/adverse effects ; Smoking ; }, abstract = {The soluble mesothelin-related peptide (SMRP), a candidate marker for screening of subjects with asbestos exposure, is influenced by some individual and clinical factors. The aim of this study was to quantify the role of age, smoking, weight, presence of diseases and exposure to asbestos on serum SMRP levels in a large series of subjects exposed to asbestos, possible candidates for mesothelioma screening. One thousand seven hundred and four participants underwent clinical examination and were interviewed on medical anamnesis, occupation, smoking and weight. SMRP was measured by an ELISA assay. Overall, median SMRP was 0.4 (IQR 25-75: 0.3-0.7) nmol/l. It was higher in current smokers and in subjects with a cumulative asbestos exposure >50 ff/cc/years than in all the other subjects (p < 0.001 and p = 0.002, respectively). SMRP was positively correlated with age (ρ = 0.11, p < 0.001) and, inversely, with BMI (ρ = -0.15, p < 0.001). SMRP was lower in healthy subjects (n = 1,217: median 0.4 nmol/l) than in subjects with malignant tumors (n = 118: 0.5 nmol/l; p = 0.01), asbestos-related pleural lesions (plaques or thickenings, n = 152: 0.6 nmol/l; p < 0.001) and other benign diseases (n = 182: 0.5 nmol/l; p = 0.04). Multivariate analysis revealed significant predictors of increased SMRP: age >57 years, current smoking, a positive anamnesis for cancer and for asbestos-related pleural lesions, and BMI < 25. Some clinical and demographic variables are associated with serum SMRP levels. The degree of these associations is low, nevertheless they should be accounted for in the interpretation of SMPR as a candidate marker predictive of mesothelioma. The potential predictive value of serum SMRP in screening/surveillance programs must be validated in prospective studies.}, } @article {pmid23276688, year = {2013}, author = {Remon, J and Lianes, P and Martínez, S and Velasco, M and Querol, R and Zanui, M}, title = {Malignant mesothelioma: new insights into a rare disease.}, journal = {Cancer treatment reviews}, volume = {39}, number = {6}, pages = {584-591}, doi = {10.1016/j.ctrv.2012.12.005}, pmid = {23276688}, issn = {1532-1967}, mesh = {Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use ; Humans ; Mesothelioma/drug therapy/*pathology/*therapy ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare and aggressive malignancy of the pleura associated with exposure to asbestos. Its incidence is anticipated to increase over the next 10years in both Europe and the developing nations. In advanced disease, chemotherapy is the cornerstone of treatment, especially platinum-containing regimens. Most efforts are directed toward improving standard first-line therapy or developing effective second-line therapy, which is still not yet standardized 10years after the first-line standard of care was established. This review focuses on the systemic management of MPM in patients who are not considered suitable for surgical approaches, and it discusses some questions that remain open such as the benefits of administering a maintenance treatment, whether it is better to give cisplatin or carboplatin as first-line therapy, the role of new drugs as second-line therapy, and the treatment of the elderly population. It also summarizes the results from clinical trials that have evaluated new treatments as first- or second-line therapy, which are based on the understanding of mesothelioma biology, such as antiangiogenic drugs, immunotherapies and growth factors agents.}, } @article {pmid23272646, year = {2012}, author = {Okonogi, N and Ebara, T and Ishikawa, H and Yoshida, D and Ueno, M and Maeno, T and Suga, T and Nakano, T}, title = {A seven-year disease-free survivor of malignant pleural mesothelioma treated with hyperthermia and chemotherapy: a case report.}, journal = {Journal of medical case reports}, volume = {6}, number = {}, pages = {427}, pmid = {23272646}, issn = {1752-1947}, abstract = {INTRODUCTION: Malignant pleural mesothelioma was once a rare finding but its incidence is increasing worldwide, most likely because of widespread exposure to asbestos. Although complete surgical resection is considered the only curative treatment, the results of surgery have shown a median survival time of only one year. In inoperable cases, chemotherapy, radiotherapy, and a combination of both have been considered as palliative therapy. Therefore, outcomes for inoperable cases have been poor. Here, we report the case of a long-term survivor treated with hyperthermia and chemotherapy.

CASE PRESENTATION: A 61-year-old Japanese man with a performance status of 1 due to chest pain was referred to our hospital. He had a history of asbestos exposure for approximately five years. A computed tomography scan showed diffuse extensive right pleural thickening with small nodular lesions, and video-assisted thoracoscopy revealed tumor invasion of the ipsilateral chest wall muscles. The histopathologic findings were consistent with a diagnosis of malignant pleural mesothelioma (sarcomatoid type). The tumor was diagnosed as being stage cT3N0M0. Our patient refused any invasive therapies including surgery and radiotherapy, and was therefore treated with hyperthermia and systemic chemotherapy with agents such as cisplatin and irinotecan. He underwent three hyperthermia sessions and a single course of chemotherapy without any severe complications. One month after treatment, a follow-up computed tomography scan showed no definitive abnormality in the thoracic space. Our patient has subsequently survived without any evident disease for more than seven years.

CONCLUSIONS: The combination of hyperthermia and chemotherapy may be a novel and safe therapeutic option for malignant pleural mesothelioma, and can be considered for patients ineligible for radical treatment. Further clinical studies of the combination of hyperthermia and chemotherapy are needed to confirm the effects of this treatment on malignant pleural mesothelioma.}, } @article {pmid23259649, year = {2012}, author = {Petrausch, U and Schuberth, PC and Hagedorn, C and Soltermann, A and Tomaszek, S and Stahel, R and Weder, W and Renner, C}, title = {Re-directed T cells for the treatment of fibroblast activation protein (FAP)-positive malignant pleural mesothelioma (FAPME-1).}, journal = {BMC cancer}, volume = {12}, number = {}, pages = {615}, pmid = {23259649}, issn = {1471-2407}, mesh = {Adolescent ; Adoptive Transfer ; Adult ; Aged ; Cytokines/metabolism ; Endopeptidases ; Female ; Gelatinases/*metabolism ; Humans ; Immunotherapy, Adoptive/*methods ; Male ; Membrane Proteins/*metabolism ; Mesothelioma/immunology/metabolism/*therapy ; Middle Aged ; Pleural Effusion ; Pleural Effusion, Malignant ; Pleural Neoplasms/immunology/metabolism/*therapy ; Serine Endopeptidases/*metabolism ; T-Lymphocytes/*immunology ; Young Adult ; }, abstract = {BACKGROUND: Asbestos is the main cause of MPM in industrialized countries. Even since asbestos is banned in most developed countries, the peak wave of MPM incidence is anticipated for the next years due to the long latency of asbestos induced MPM. MPM patients not eligible for surgical procedures like decortication or pleuro-pneumectomie have a median survival of 12 months with palliative chemotherapy. Therefore, new therapeutic approaches are of crucial need in this clinical situation.

METHODS/DESIGN: This is a phase I trial for patients with malignant pleural mesothelioma with pleural effusion testing the safety of a fixed single dose of 1x106 adoptively transferred FAP-specific re-directed T cells given directly in the pleural effusion. Lymphocytes will be taken 21 days before transfer from peripheral blood. CD8 positive T cells will be isolated and re-programmed by retroviral transfer of a chimeric antigen receptor recognizing FAP which serves as target structure in MPM. At day 0 of the protocol, re-directed T cells will be injected in the pleural effusion and patients will be monitored for 48h under intermediate care conditions. AE, SAE, SADR and SUSAR will be monitored for 35 days and evaluated by an independent safety board to define any dose limiting toxicity (DLT). No further patient can be treated before the previous patient passed day 14 after T cell transfer. The protocol will be judged as save when no DLT occurred in the first 3 patients, or 1 DLT in 6 patients. Secondary objectives are feasibility and immune monitoring.

DISCUSSION: Adoptive T cell transfer is a new and rapidly expanding branch of immunotherapies focusing on cancer treatment. Recently, objective responses could be observed in patients with chronic lymphatic leukemia treated with adoptively transferred CD19-specific re-directed T cells. The choice of the target antigen determines the possible on-target off-tissue toxicity of such approaches. There are reports of severe toxicity in patients who received T cells intravenously due to unexpected expression of the target antigen (on-target) in other tissues than the tumor (off-tissue). To minimize the risk of on-target off-tissue toxicity and to maximize the on-target anti-tumor effect we propose a clinical protocol with loco-regional administration of re-directed T cells. FAP-specific T cells will be directly injected in the pleural effusion of patients with MPM.

TRIAL REGISTRATION: ClinicalTrials.gov (NCT01722149).}, } @article {pmid23259393, year = {2012}, author = {Morimoto, C and Ohnuma, K}, title = {[Antibody therapy for malignant mesothelioma: humanized anti-cD26 mAb therapy].}, journal = {Nihon rinsho. Japanese journal of clinical medicine}, volume = {70}, number = {12}, pages = {2177-2182}, pmid = {23259393}, issn = {0047-1852}, mesh = {Animals ; Antibodies, Monoclonal/*therapeutic use ; Antibodies, Monoclonal, Humanized/biosynthesis/*therapeutic use ; Dipeptidyl Peptidase 4/*immunology ; Humans ; Mesothelioma/*drug therapy/immunology ; Pleural Neoplasms/drug therapy/immunology ; Treatment Outcome ; }, abstract = {Malignant mesothelioma (MM) is an aggressive malignancy arising from the mesothelial cells. It is generally associated with a history of asbestos exposure and has a very poor prognosis. Due to lack of efficacy of conventional treatments, novel therapeutic strategies are urgently needed to improve outcomes. Recently we showed that CD26 is preferentially expressed on epithelial type of MM cells but not on normal mesothelial cells. We have developed a highly biological active humanized anti-CD26 mAb and this antibody inhibited growth and invasion of MM cells and induced long-term survival of tumor transplanted SCID mice. It is conceivable that CD26 is a new therapeutic target for MM. Phase I/II clinical trial for MM has been already starting in France and we plan to start the clinical trial for MM as soon as possible in Japan.}, } @article {pmid23256650, year = {2012}, author = {Vyas, D and Pihl, K and Kavuturu, S and Vyas, A}, title = {Mesothelioma as a rapidly developing Giant Abdominal Cyst.}, journal = {World journal of surgical oncology}, volume = {10}, number = {}, pages = {277}, pmid = {23256650}, issn = {1477-7819}, mesh = {Abdominal Neoplasms/*diagnosis/surgery ; Humans ; Male ; Mesothelioma, Cystic/*diagnosis/surgery ; Middle Aged ; Peritoneal Neoplasms/*diagnosis/surgery ; Prognosis ; }, abstract = {The benign cystic mesothelioma of the peritoneum is a rare lesion and is known for local recurrence. This is first case report of a rapidly developing massive abdominal tumor with histological finding of benign cystic mesothelioma (BCM). We describe a BCM arising in the retroperitoneal tis[sue on the right side, lifting ascending colon and cecum to the left side of abdomen. Patient was an active 58-year-old man who noticed a rapid abdominal swelling within a two month time period with a weight gain of 40 pounds. Patient had no risk factors including occupational (asbestos, cadmium), family history, social (alcohol, smoking) or history of trauma. We will discuss the clinical, radiologic, intra-operative, immunohistochemical, pathologic findings, and imaging six months after surgery. Patient has no recurrence and no weight gain on follow up visits and imaging.}, } @article {pmid23244777, year = {2013}, author = {Pinto, C and Novello, S and Torri, V and Ardizzoni, A and Betta, PG and Bertazzi, PA and Casalini, GA and Fava, C and Fubini, B and Magnani, C and Mirabelli, D and Papotti, M and Ricardi, U and Rocco, G and Pastorino, U and Tassi, G and Trodella, L and Zompatori, M and Scagliotti, G}, title = {Second Italian consensus conference on malignant pleural mesothelioma: state of the art and recommendations.}, journal = {Cancer treatment reviews}, volume = {39}, number = {4}, pages = {328-339}, doi = {10.1016/j.ctrv.2012.11.004}, pmid = {23244777}, issn = {1532-1967}, mesh = {Humans ; Italy/epidemiology ; Mesothelioma/*diagnosis/epidemiology/*therapy ; Pleural Neoplasms/*diagnosis/epidemiology/*therapy ; Public Health ; }, abstract = {Malignant pleural mesothelioma (MPM) is a relevant public health issue. A large amount of data indicate a relationship between mesothelioma and asbestos exposure. MPM incidence has considerably and constantly increased over the past two decades in industrialized countries and is expected to peak in 2010-2020. In Italy, the standardized incidence rate in 2008 was 3.6 and 1.3 per 100,000 in men and women respectively, with wide differences from one region to another. The approach to this disease remains difficult and complex in terms of pathogenic mechanism, diagnosis, staging and treatment thus an optimal strategy has not yet been clearly defined. The Second Italian Multidisciplinary Consensus Conference on Malignant Pleural Mesothelioma was held in Turin (Italy) on November 24-25, 2011: recommendations on MPM management for public health institutions, clinicians and patients are presented in this report.}, } @article {pmid23244069, year = {2012}, author = {Bianchi, C and Bianchi, T}, title = {Malignant mesothelioma in Eastern Asia.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {13}, number = {10}, pages = {4849-4853}, doi = {10.7314/apjcp.2012.13.10.4849}, pmid = {23244069}, issn = {2476-762X}, mesh = {Asia, Eastern/epidemiology ; Humans ; Mesothelioma/*epidemiology ; Pleural Neoplasms/*epidemiology ; }, abstract = {Relatively low numbers of malignant mesotheliomas have been reported from Eastern Asia. In order to explore the causes of this fact, the available data on mesothelioma incidence/mortality in five countries (Japan, South Korea, Taiwan, Hong Kong, and Singapore) were reviewed. Data on the industrial histories of the above countries were also examined. Mesothelioma incidence was low, despite a history of high shipbuilding and port activities, in which heavy exposure to asbestos generally has occurred. Underestimation of mesothelioma could partly explain the above discrepancy. Moreover, in some areas a sufficient latency period for mesothelioma development may have not yet elapsed, due to recent industrialization. However, other possibilities have to be considered. The cancer epidemiology in Eastern Asia differs deeply from that seen in Western countries, an indication of differences in etiologic factors of cancer as well as in co-factors. In addition, the oncogenic spectrum of asbestos is wide, and not completely defined. In a very different milieu from that of Western countries, asbestos could preferentially hit targets other than serosal membranes.}, } @article {pmid23232815, year = {2013}, author = {Williams, C and Dell, L and Adams, R and Rose, T and Van Orden, D}, title = {State-of-the-science assessment of non-asbestos amphibole exposure: is there a cancer risk?.}, journal = {Environmental geochemistry and health}, volume = {35}, number = {3}, pages = {357-377}, pmid = {23232815}, issn = {1573-2983}, mesh = {Animals ; Asbestos, Amphibole/*toxicity ; Bias ; Environmental Exposure/*adverse effects ; Humans ; Lung/metabolism ; Lung Neoplasms/epidemiology/*etiology ; Mesothelioma/epidemiology/etiology ; Risk Assessment/methods ; Time Factors ; }, abstract = {The distinction between amphibole asbestos fibers and non-asbestos amphibole particles has important implications for assessing potential cancer risks associated with exposure to amphibole asbestos or amphibole-containing products. Exposure to amphibole asbestos fibers can pose a cancer risk due to its ability to reside for long periods of time in the deep lung (i.e., biopersistence). In contrast, non-asbestos amphibole particles are usually cleared rapidly from the lung and do not pose similar respiratory risks even at high doses. Most regulatory and public health agencies, as well as scientific bodies, agree that non-asbestos amphiboles possess reduced biological (e.g., carcinogenic) activity. Although non-asbestos amphibole minerals have been excluded historically from Federal regulations, non-asbestos structures may be counted as asbestos fibers on the basis of dimensional criteria specified in analytical protocols. Given the potential to mischaracterize a non-asbestos structure as a "true" asbestos fiber, our objective was to assess whether exposure to non-asbestos amphiboles that may meet the dimensional criteria for counting as a fiber pose a cancer risk similar to amphibole asbestos. We reviewed analytical methods as well as the mineralogical, epidemiological, and toxicological literature for non-asbestos amphiboles. No evidence of demonstrable cancer effects from exposure to non-asbestos amphiboles that may be counted as fibers, under certain assessment protocols, was found. Data gaps (industrial hygiene data for amphibole-exposed cohorts), inconsistencies (analytical laboratory methods/protocols used to count fibers), and sources of potential bias from misclassification of exposure were identified.}, } @article {pmid23232263, year = {2013}, author = {Shiota, H and Yasukawa, T and Hirai, A and Chiyo, M and Yusa, T and Hiroshima, K}, title = {Extraskeletal osteosarcoma of the pleura:report of a case.}, journal = {Annals of thoracic and cardiovascular surgery : official journal of the Association of Thoracic and Cardiovascular Surgeons of Asia}, volume = {19}, number = {4}, pages = {297-301}, doi = {10.5761/atcs.cr.12.01964}, pmid = {23232263}, issn = {2186-1005}, mesh = {Aged ; Asbestos/adverse effects ; Biomarkers, Tumor/analysis ; Biopsy ; Diagnosis, Differential ; Humans ; Immunohistochemistry ; Male ; Osteosarcoma/chemistry/etiology/*pathology/surgery ; Pleural Neoplasms/chemistry/etiology/*pathology/surgery ; Predictive Value of Tests ; Tomography, X-Ray Computed ; }, abstract = {Extraskeletal osteosarcoma is a rare malignant tumor occurring very rarely in the pleura. We herein report the case of 67-year-old man with asbestos exposure, who underwent biopsies of the large tumor from the chest wall, and diagnosed as a suspicious of fibrosarcoma. Surgical resection was done, and the pathological diagnosis was extraskeletal osteosarcoma arising from the pleura. The differential diagnosis is malignant pleural mesothelioma with osseous and cartilaginous which is also very rare and one of the histopathological subtypes with heterologous elements. Identification of epithelial components, labeling for cytokeratins in spindle cells and its' anatomical distribution may help to distinguish them. In the neoplasm arising from the parietal pleura, primary extraskeletal osteosarcoma of the pleura is very rare, but should be considered.}, } @article {pmid23207475, year = {2012}, author = {Thomas, D and Geck, R and Rozas, D and Muro-Cacho, C and Rumbak, M}, title = {Mesothelioma: a soon to be forgotten disease in the United States?.}, journal = {Journal of bronchology & interventional pulmonology}, volume = {19}, number = {3}, pages = {258-261}, doi = {10.1097/LBR.0b013e31825f1aba}, pmid = {23207475}, issn = {1948-8270}, mesh = {Aged, 80 and over ; Asbestos/*adverse effects ; Construction Industry ; Humans ; Male ; Mesothelioma/*diagnosis/pathology ; Occupational Diseases/*diagnosis/pathology ; Occupational Exposure/*adverse effects ; Pleural Effusion, Malignant/diagnostic imaging ; Pleural Neoplasms/*diagnosis/pathology ; Thoracoscopy ; Tomography, X-Ray Computed ; United States ; }, abstract = {Malignant pleural mesothelioma is an uncommon cancer that commonly presents with a large unilateral bloody pleural effusion long after asbestos exposure. Its prevalence is decreasing with the decreasing exposure to asbestos in the United States. We present a patient with malignant pleural mesothelioma who underwent evaluation and treatment during medical thoracoscopy. The thoracoscopic evaluation revealed multiple, varied, and severe but characteristic findings of malignant pleural mesothelioma. Medical thoracoscopy is the procedure of choice for the diagnosis of pleural mesothelioma.}, } @article {pmid23206832, year = {2013}, author = {Roca, E and Laroumagne, S and Vandemoortele, T and Berdah, S and Dutau, H and Maldonado, F and Astoul, P}, title = {18F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography fused imaging in malignant mesothelioma patients: looking from outside is not enough.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {79}, number = {2}, pages = {187-190}, doi = {10.1016/j.lungcan.2012.10.017}, pmid = {23206832}, issn = {1872-8332}, mesh = {Aged ; False Negative Reactions ; Fluorodeoxyglucose F18 ; Humans ; Laparoscopy ; Male ; Mesothelioma/*diagnostic imaging/*pathology ; Middle Aged ; *Multimodal Imaging ; Peritoneal Neoplasms/*diagnostic imaging/*pathology ; Pleural Neoplasms/*diagnostic imaging/*pathology ; *Positron-Emission Tomography ; Radiopharmaceuticals ; Thoracoscopy ; *Tomography, X-Ray Computed ; }, abstract = {Malignant mesothelioma (MM) is an uncommon neoplasm with a poor prognosis usually associated with asbestos exposure. 18F-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET)/computed tomography (CT) has become an invaluable tool for the diagnosis, staging, and prognosis of this severe disease as it combines both anatomic and functional information in a single imaging procedure, allowing for improved management of this disease. For many authors, 18F-FDG-PET/CT is the cornerstone of the pre-therapeutic evaluation of mesothelioma patients, particularly when multimodal therapy (including extra-pleural pneumonectomy or omentectomy) is considered. However, while characteristic patterns have been reported as predictive of macroscopic pleural or peritoneal involvement, false negative findings are possible, both for pleural and peritoneal mesothelioma, during the initial diagnosis or during the patient's surveillance as illustrated by this report of three cases of suspected MM with negative PET/CT. This report highlights the limitations of PET/CT in the diagnostic evaluation of MM and the importance of histopathological confirmation by thoracoscopy and/or laparoscopy, which remain the most important diagnostic procedures in MM.}, } @article {pmid23205076, year = {2012}, author = {Saeki, H and Hashizume, A and Izumi, H and Suzuki, F and Ishi, K and Nojima, M and Maeda, M and Hino, O}, title = {The utility of serum N-ERC/mesothelin as a biomarker of ovarian carcinoma.}, journal = {Oncology letters}, volume = {4}, number = {4}, pages = {637-641}, pmid = {23205076}, issn = {1792-1074}, abstract = {Ovarian carcinoma has been difficult to diagnose at an early stage. Recently, it has been recognized that the measurement of blood N-ERC/mesothelin levels aids early detection in and postoperative therapeutic monitoring of patients with mesothelioma, who have been exposed to asbestos. ERC/mesothelin has also been reported to be expressed in ovarian carcinoma. We determined serum N-ERC/mesothelin levels in patients with ovarian carcinoma using an enzyme-linked immunosorbent assay (ELISA). In addition, we immunohistochemically evaluated surgically resected specimens for C-ERC/mesothelin expression. As a result, of the 32 patients with ovarian tumors (18 carcinoma, 2 borderline tumors), one patient with serous adenocarcinoma showed increased N-ERC/ mesothelin levels. Immunohistochemically, of the 20 ovarian tumor (carcinoma and borderline tumor) specimens evaluated for serum N-ERC/mesothelin, 9 (45.0%) were positive for C-ERC/mesothelin. The C-ERC/mesothelin-positive specimens were found to be serous and clear cell adenocarcinomas. If serum N-ERC/mesothelin, which is considered useful for early detection in and therapeutic monitoring of patients with mesothelioma, may also be used for ovarian carcinoma monitoring, it may be a valuable serum tumor marker for the early detection of ovarian carcinoma.}, } @article {pmid23200587, year = {2012}, author = {De Vuyst, P and Remmelink, M and Mekinda, Z and Thimpont, J and Dumortier, P and Gevenois, PA}, title = {[Asbestosis still exists…].}, journal = {Revue des maladies respiratoires}, volume = {29}, number = {9}, pages = {1127-1131}, doi = {10.1016/j.rmr.2012.04.008}, pmid = {23200587}, issn = {1776-2588}, mesh = {Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use ; Asbestos, Amosite/adverse effects/analysis ; Asbestosis/complications/*diagnosis/diagnostic imaging/pathology/surgery ; Bronchoalveolar Lavage Fluid/chemistry ; Carcinoma, Bronchogenic/drug therapy/etiology/pathology/surgery ; Cisplatin/administration & dosage/adverse effects ; Combined Modality Therapy ; Female ; Humans ; Incidental Findings ; Industry ; Lung/pathology ; Lung Neoplasms/drug therapy/etiology/pathology/surgery ; Middle Aged ; Mineral Fibers/adverse effects/analysis ; Occupational Exposure ; Pleura/pathology ; Pulmonary Aspergillosis/etiology ; Respiratory Function Tests ; Tomography, X-Ray Computed ; Vinblastine/administration & dosage/adverse effects/analogs & derivatives ; Vinorelbine ; }, abstract = {A diagnosis of asbestosis, lung fibrosis due to asbestos exposure, was proposed in 2003 in a 64-year-old woman on the basis of the history, computed tomography appearances, lung function studies, and biometric data. This diagnosis was confirmed by the pathological examination of a lung lobe resected surgically for bronchial carcinoma in 2010. The diagnosis of asbestosis is now rarely made as a result of a substantial decrease in dust exposure over the past decades and mainly because of the interdiction of asbestos use in western countries. Currently, the most frequent thoracic manifestations of asbestos exposure are benign pleural lesions and mesothelioma. It has also become exceptional to have pathological confirmation of the diagnosis, obtained in this woman thanks to the surgical treatment of another complication of her occupational exposure.}, } @article {pmid23192535, year = {2013}, author = {Choi, Y and Lim, S and Paek, D}, title = {Trades of dangers: a study of asbestos industry transfer cases in Asia.}, journal = {American journal of industrial medicine}, volume = {56}, number = {3}, pages = {335-346}, doi = {10.1002/ajim.22144}, pmid = {23192535}, issn = {1097-0274}, mesh = {Adult ; *Air Pollutants, Occupational/adverse effects/analysis ; *Asbestos/adverse effects/analysis ; Asbestosis/etiology/mortality/prevention & control ; Commerce ; *Developed Countries ; *Developing Countries ; Female ; Germany ; Health Surveys ; Humans ; Indonesia ; Japan ; Lung Neoplasms/etiology/mortality/prevention & control ; Male ; Mesothelioma/etiology/mortality/prevention & control ; Middle Aged ; Occupational Exposure/adverse effects/analysis/legislation & jurisprudence/prevention & control/*standards ; Occupational Health/legislation & jurisprudence/*standards ; Republic of Korea ; Textile Industry/legislation & jurisprudence/*standards ; }, abstract = {BACKGROUND: In a study of asbestos industry transfers in Asia, we examined the transfer of health and safety measures at the time of industry transfer and resulting health outcomes thereafter.

METHODS: Field surveys were conducted in Japan, Germany, Indonesia, and South Korea over a 5 year period beginning in 2007. The surveys involved interviews and field assessments of health and safety conditions.

RESULTS: Even when there were transfers of entire engineering plant processes, we observed that the health and safety measures that should have accompanied the transfer, including technical capacities of risk assessment and management, regulatory protection, and cultural practices, were not actually transferred. According to work environment assessment records, there were differences in airborne asbestos levels of approximately 5-6 fibers/cc between the exporting and importing sides of the transfer. This amounted to a 10 years of time delay in comparable health and safety conditions. These differences resulted in repeated adverse health consequences at each factory operation site.

CONCLUSIONS: Dangerous transfers of asbestos industry technology have occurred repeatedly over the years with the result that Asia has become the largest consumer of asbestos in the world. No effective internationally accepted safety measures have been introduced in the region. The study results support the need for both improved public awareness and international cooperation, such as sharing of substitute material technologies by the exporting countries, and provide the rationale for the creation of an Asian fund for asbestos victims.}, } @article {pmid23187858, year = {2013}, author = {van der Bij, S and Koffijberg, H and Lenters, V and Portengen, L and Moons, KG and Heederik, D and Vermeulen, RC}, title = {Lung cancer risk at low cumulative asbestos exposure: meta-regression of the exposure-response relationship.}, journal = {Cancer causes & control : CCC}, volume = {24}, number = {1}, pages = {1-12}, doi = {10.1007/s10552-012-0107-7}, pmid = {23187858}, issn = {1573-7225}, mesh = {Asbestos/toxicity ; Asbestosis/*complications/epidemiology ; Carcinogens, Environmental/toxicity ; Environmental Exposure/adverse effects ; Humans ; Lung Neoplasms/epidemiology/*etiology ; Mesothelioma/epidemiology/*etiology ; Occupational Exposure/adverse effects ; Regression Analysis ; Risk Assessment ; Risk Factors ; }, abstract = {PURPOSE: Existing estimated lung cancer risks per unit of asbestos exposure are mainly based on, and applicable to, high exposure levels. To assess the risk at low cumulative asbestos exposure, we provide new evidence by fitting flexible meta-regression models, a notably new and more robust method.

METHODS: Studies were selected if lung cancer risk per cumulative asbestos exposure in at least two exposure categories was reported. From these studies (n = 19), we extracted 104 risk estimates over a cumulative exposure range of 0.11-4,710 f-y/ml. We fitted linear and natural spline meta-regression models to these risk estimates. A natural spline allows risks to vary nonlinearly with exposure, such that estimates at low exposure are less affected by estimates in the upper exposure categories. Associated relative risks (RRs) were calculated for several low cumulative asbestos exposures.

RESULTS: A natural spline model fitted our data best. With this model, the relative lung cancer risk for cumulative exposure levels of 4 and 40 f-y/ml was estimated between 1.013 and 1.027, and 1.13 and 1.30, respectively. After stratification by fiber type, a non-significant three- to fourfold difference in RRs between chrysotile and amphibole fibers was found for exposures below 40 f-y/ml. Fiber-type-specific risk estimates were strongly influenced by a few studies.

CONCLUSIONS: The natural spline regression model indicates that at lower asbestos exposure levels, the increase in RR of lung cancer due to asbestos exposure may be larger than expected from previous meta-analyses. Observed potency differences between different fiber types are lower than the generally held consensus. Low-exposed industrial or population-based cohorts with quantitative estimates of asbestos exposure a required to substantiate the risk estimates at low exposure levels from our new, flexible meta-regression.}, } @article {pmid23187004, year = {2012}, author = {Lee, YJ and Im, JH and Lee, DM and Park, JS and Won, SY and Cho, MK and Nam, HS and Lee, YJ and Lee, SH}, title = {Synergistic inhibition of mesothelioma cell growth by the combination of clofarabine and resveratrol involves Nrf2 downregulation.}, journal = {BMB reports}, volume = {45}, number = {11}, pages = {647-652}, pmid = {23187004}, issn = {1976-670X}, mesh = {Adenine Nucleotides/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/*pharmacology ; Apoptosis/drug effects ; Arabinonucleosides/administration & dosage ; Blotting, Western ; Cell Proliferation/*drug effects ; Clofarabine ; Down-Regulation ; Drug Synergism ; Heme Oxygenase-1/metabolism ; Humans ; Mesothelioma/drug therapy/metabolism/*pathology ; NF-E2-Related Factor 2/antagonists & inhibitors/genetics/*metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; RNA, Small Interfering/genetics ; Resveratrol ; Signal Transduction/*drug effects ; Stilbenes/administration & dosage ; Tumor Cells, Cultured ; }, abstract = {We previously reported that MSTO-211H cells have a higher capacity to regulate Nrf2 activation in response to changes in the cellular redox environment. To further characterize its biological significance, the response of Nrf2, a transcription factor that regulates ARE-containing genes, on the synergistic cytotoxic effect of clofarabine and resveratrol was investigated in mesothelioma cells. The combination treatment showed a marked growth-inhibitory effect, which was accompanied by suppression of Nrf2 activation and decreased expression of heme oxygenase-1 (HO-1). While transient overexpression of Nrf2 conferred protection against the cytotoxicity caused by their combination, knockdown of Nrf2 expression using siRNA enhanced their cytotoxic effect. Pretreatment with Ly294002, a PI3K inhibitor, augmented the decrease in HO-1 level by their combination, whereas no obvious changes were observed in Nrf2 levels. Altogether, these results suggest that the synergistic cytotoxic effect of clofarabine and resveratrol was mediated, at least in part, through suppression of Nrf2 signaling.}, } @article {pmid23170051, year = {2012}, author = {Kubo, Y and Takenaka, H and Nagai, H and Toyokuni, S}, title = {Distinct affinity of nuclear proteins to the surface of chrysotile and crocidolite.}, journal = {Journal of clinical biochemistry and nutrition}, volume = {51}, number = {3}, pages = {221-226}, pmid = {23170051}, issn = {1880-5086}, abstract = {The inhalation of asbestos is a risk factor for the development of malignant mesothelioma and lung cancer. Based on the broad surface area of asbestos fibers and their ability to enter the cytoplasm and nuclei of cells, it was hypothesized that proteins that adsorb onto the fiber surface play a role in the cytotoxicity and carcinogenesis of asbestos fibers. However, little is known about which proteins adsorb onto asbestos. Previously, we systematically identified asbestos-interacting proteins and classified them into eight sub-categories: chromatin/nucleotide/RNA-binding proteins, ribosomal proteins, cytoprotective proteins, cytoskeleton-associated proteins, histones and hemoglobin. Here, we report an adsorption profile of proteins for the three commercially used asbestos compounds: chrysotile, crocidolite and amosite. We quantified the amounts of adsorbed proteins by analyzing the silver-stained gels of sodium dodecyl sulfate-polyacrylamide gel electrophoresis with ImageJ software, using the bands for amosite as a standard. We found that histones were most adsorptive to crocidolite and that chromatin-binding proteins were most adsorptive to chrysotile. The results suggest that chrysotile and crocidolite directly interact with chromatin structure through different mechanisms. Furthermore, RNA-binding proteins preferably interacted with chrysotile, suggesting that chrysotile may interfere with transcription and translation. Our results provide novel evidence demonstrating that the specific molecular interactions leading to carcinogenesis are different between chrysotile and crocidolite.}, } @article {pmid23167246, year = {2013}, author = {Linton, A and Kao, S and Vardy, J and Clarke, S and van Zandwijk, N and Klebe, S}, title = {Immunohistochemistry in the diagnosis of malignant pleural mesothelioma: trends in Australia and a literature review.}, journal = {Asia-Pacific journal of clinical oncology}, volume = {9}, number = {3}, pages = {273-279}, doi = {10.1111/ajco.12043}, pmid = {23167246}, issn = {1743-7563}, mesh = {Australia ; Cohort Studies ; Humans ; Immunohistochemistry/trends ; Lung Neoplasms/*diagnosis/metabolism/pathology/surgery ; Mesothelioma/*diagnosis/metabolism/pathology/surgery ; Mesothelioma, Malignant ; Pleural Neoplasms/*diagnosis/metabolism/pathology/surgery ; }, abstract = {AIMS: The accurate diagnosis of malignant pleural mesothelioma (MPM) is essential for therapeutic and legal reasons. In 2006 the International Mesothelioma Panel advocated the use of a panel, including two mesothelial and two non-mesothelial immunohistochemical (IHC) markers. We assessed the changing use of IHC for the diagnosis of MPM in Australia over two decades in the context of current best practice.

METHODS: Patients with a confirmed clinico-pathological diagnosis of MPM who underwent extrapleural pneumonectomy or pleurectomy and/or decortication between 1988 and 2006 were identified from the cardiothoracic database at Royal Prince Alfred Hospital and combined with consecutive patients reviewed by the Dust Diseases Board between March 2007 and March 2009. Initial diagnostic pathology reports were reviewed.

RESULTS: A total of 289 patients were identified. A median of six IHC stains per sample was performed (range 0-18): two (range 0-5) mesothelial markers, two (0-6) carcinoma markers and two epithelial markers. A trend to the higher usage of antibodies in epithelioid tumors versus biphasic and sarcomatoid tumors was noted (P = 0.148 and 0.389, respectively). Testing increased from a median of three stains per sample (1988-1997) to seven (2006-2009). Labeling specimens with > 2 mesothelial markers and > 2 carcinoma markers increased to 72 and 67 percent, respectively, after 2006.

CONCLUSION: Reflecting the acceptance of diagnostic panels and increased availability of antibodies, an increase in the use of IHC stains for MPM diagnosis has occurred over the past two decades although uncertainty persists as to the optimal panel composition.}, } @article {pmid23154557, year = {2012}, author = {Helland, Å and Solberg, S and Brustugun, OT}, title = {Incidence and survival of malignant pleural mesothelioma in norway: a population-based study of 1686 cases.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {7}, number = {12}, pages = {1858-1861}, doi = {10.1097/JTO.0b013e318275b346}, pmid = {23154557}, issn = {1556-1380}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Carboplatin/administration & dosage ; Cisplatin/administration & dosage ; Female ; Follow-Up Studies ; Humans ; Incidence ; Male ; Mesothelioma/drug therapy/epidemiology/*mortality ; Norway/epidemiology ; Pleural Neoplasms/drug therapy/epidemiology/*mortality ; Prognosis ; Registries ; Survival Rate ; Time Factors ; }, abstract = {BACKGROUND: Asbestos-related malignant pleural mesothelioma is one of the most lethal tumor types. The advent of antimetabolite treatment as pemetrexed, introduced in the early 2000s, may have increased survival on a population basis. In this study, we have analyzed population-based incidence and survival data over the last 40 years.

METHODS: Complete national data on 1686 patients from the Cancer Registry of Norway sampled from 1970 to 2009 are presented, with incidence rates in 5-year periods. Relative survival for 1 year and 3 years and median survival in 5-year intervals were calculated.

RESULTS: The incidence of malignant pleural mesothelioma has been significantly and steadily increasing from 1970 until 2009, with 50 patients diagnosed in the period 1970-1974 and 377 diagnosed in 2005-2009. The incidence was highest among men in all time periods. A slight decline was observed in the last period. The 1-year survival rate increased from 20.7% to 44.0% during the period 1970-2009, whereas the 3-year survival rate remained below 10%. Median survival increased from 4.0 months in the first period to 9.3 months in the last period.

CONCLUSIONS: The incidence of malignant pleural mesothelioma follows the curve of asbestos exposure with a 20- to 40-year lag. There has been a significant increase in survival, most likely because of earlier diagnosis and improvements in cytostatic treatment.}, } @article {pmid23139709, year = {2012}, author = {Terada, T and Tabata, C and Tabata, R and Okuwa, H and Kanemura, S and Shibata, E and Nakano, T}, title = {Clinical utility of 18-fluorodeoxyglucose positron emission tomography/computed tomography in malignant pleural mesothelioma.}, journal = {Experimental and therapeutic medicine}, volume = {4}, number = {2}, pages = {197-200}, pmid = {23139709}, issn = {1792-0981}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive malignant tumor of mesothelial origin associated with asbestos exposure. MPM has a limited response to conventional chemotherapy and radiotherapy, thus early diagnosis of MPM is extremely critical. CT scans have limited accuracy in the differentiation between benign and malignant pleural disease. Several studies have reported that 18-fluorodeoxyglucose (FDG) positron emission tomography (PET) plays an important role in the assessment of thoracic malignancy such as lung cancer. Here, we investigated the clinical utility of PET in patients with MPM. The maximum SUV (SUVmax) of 18F-FDG was measured in 47 MPM patients and 29 non-MPM patients including those with pleural thickening. We demonstrated that patients with MPM had significantly higher SUVmax levels than a population with non-malignant pleural disease. The Kaplan-Meier method revealed significant differences in overall survival between groups with SUVmax levels lower and higher than the assumed cut-off. Our data suggest that SUVmax levels are useful as an aid for diagnosis and prognosis of MPM.}, } @article {pmid23130478, year = {2012}, author = {Subhannachart, P and Dumavibhat, N and Siriruttanapruk, S}, title = {Asbestos-related diseases in Thailand and review literature.}, journal = {Journal of the Medical Association of Thailand = Chotmaihet thangphaet}, volume = {95 Suppl 8}, number = {}, pages = {S71-6}, pmid = {23130478}, issn = {0125-2208}, mesh = {Aged ; Air Pollutants, Occupational/adverse effects ; *Asbestosis/diagnosis/etiology/physiopathology/prevention & control ; Health Services Needs and Demand/organization & administration ; Humans ; Male ; *Mesothelioma/etiology/pathology/physiopathology/prevention & control ; Middle Aged ; Mineral Fibers/adverse effects ; Occupational Exposure/adverse effects/*prevention & control ; Pleural Neoplasms/*pathology ; Public Health/methods ; Spirometry/methods ; Thailand ; Tomography, X-Ray Computed/methods ; }, abstract = {Asbestos is a harmful substance that can cause both malignancy and non-malignancy in humans. Although it has been used in Thailand for several years, few cases of asbestos-related diseases were reported. Concerning about high consumption and long exposure of asbestos in the country, the incurable but preventable diseases caused by asbestos will be the health problem in the near future. The authors presented 2 cases with asbestos-related diseases, one diagnosed as malignant mesothelioma and the other as asbestosis.}, } @article {pmid23121131, year = {2013}, author = {Wang, X and Lin, S and Yu, I and Qiu, H and Lan, Y and Yano, E}, title = {Cause-specific mortality in a Chinese chrysotile textile worker cohort.}, journal = {Cancer science}, volume = {104}, number = {2}, pages = {245-249}, pmid = {23121131}, issn = {1349-7006}, mesh = {Adult ; Asbestos, Serpentine/*poisoning ; China/epidemiology ; Cohort Studies ; Female ; Follow-Up Studies ; Humans ; Male ; Neoplasms/etiology/mortality ; Occupational Diseases/*etiology/*mortality ; Occupational Exposure/*adverse effects/*statistics & numerical data ; Prospective Studies ; Pulmonary Heart Disease/etiology/mortality ; Smoking/adverse effects/mortality ; Textile Industry/*statistics & numerical data ; }, abstract = {Chrysotile asbestos has continued to be mined and used in China, but its health effects on exposed workers have not been well documented. This study was conducted to give a complete picture about cause-specific mortality in Chinese asbestos workers. A cohort of 586 males and 279 females from a chrysotile textile factory were prospectively followed for 37 years. Their vital status was identified, and the date and underlying cause of death were verified from death registry. Cause-specific standardized mortality ratios by gender were computed with nationwide gender- and cause-specific mortality rates as reference. Male workers were 11 years older, and had 6 years longer exposure duration than females; 79% in males and 1% in females smoked. In males, the mortality rate of all cancers doubled; both larynx and lung cancer were four-fold, and mesothelioma was 33-fold. In females, there was slightly excess mortality from lung cancer and all cancers, and significant increase in mesothelioma and ovarian cancer. Other significantly increased mortality was seen from cancers of thymus, small intestine and penis in males, and cancers of bone and bladder in females. In addition to asbestosis, mortality from pulmonary heart disease was significantly elevated in both genders. The data confirmed significantly excess mortality from mesothelioma in either gender, lung and larynx cancers in males, and ovarian cancer in females. A gender difference in mortality from lung cancer and all cancers could be mainly due to the discrepancies in age, exposure duration and smoking between the male and female workers.}, } @article {pmid23116271, year = {2012}, author = {Llamas, MY}, title = {Tips for palliative care professionals treating mesothelioma patients.}, journal = {Journal of palliative medicine}, volume = {15}, number = {11}, pages = {1169}, doi = {10.1089/jpm.2012.9550}, pmid = {23116271}, issn = {1557-7740}, mesh = {Asbestos/adverse effects ; Caregivers/*psychology ; Consumer Health Information/*methods ; *Family Health ; Humans ; Internet ; Mesothelioma/chemically induced/*therapy ; Palliative Care/*methods ; Social Support ; Survival Rate ; }, } @article {pmid23112501, year = {2012}, author = {Bianchi, C and Bianchi, T}, title = {Shipbuilding and mesothelioma in Monfalcone, Italy.}, journal = {Indian journal of occupational and environmental medicine}, volume = {16}, number = {1}, pages = {14-17}, pmid = {23112501}, issn = {1998-3670}, abstract = {The Monfalcone area, northeastern Italy, a small industrial district with large shipyards, shows a high incidence of asbestos-related mesothelioma. In order to reconstruct some features of the Monfalcone shipbuilding activity during World War II and its health effects, the shipyard roll were examined, and people hired in 1942 were identified. The list of 2,776 persons hired in 1942 was coupled with the Pathological Anatomy Units archives of the Monfalcone and the Trieste Hospitals. Eighteen of the above persons had been diagnosed with pleural mesothelioma in the period 1981-2005. Eight patients had their first exposure in 1942, and the others had histories of previous exposures. Of 557 persons aged 14-15 years in 1942, six had a diagnosis of pleural mesothelioma. Necropsy findings were available in 14 cases. The burdens of lung asbestos bodies, isolated in 11 cases, showed wide variation (from 150 to 600,000 bodies per gram of dried tissue). While probably underestimated, the present data indicate a high incidence of mesothelioma among the shipyard workers of Monfalcone.}, } @article {pmid23101644, year = {2012}, author = {Ameille, J}, title = {[The different pleuro-pulmonary pathologies related to asbestos: definitions, epidemiology and evolution].}, journal = {Revue des maladies respiratoires}, volume = {29}, number = {8}, pages = {1035-1046}, doi = {10.1016/j.rmr.2012.02.012}, pmid = {23101644}, issn = {1776-2588}, mesh = {Adult ; Asbestos/*adverse effects ; Asbestosis/*complications/epidemiology/etiology/pathology ; Bronchial Neoplasms/epidemiology/*etiology/pathology ; Evidence-Based Medicine ; Female ; France/epidemiology ; Humans ; Male ; Mesothelioma/epidemiology/*etiology/pathology ; Pleural Neoplasms/epidemiology/*etiology/pathology ; Prognosis ; Risk Assessment ; Risk Factors ; }, abstract = {Pleural plaques (fibrosis of the parietal pleura) are sometimes seen following light exposure. Their prevalence may reach 70% in heavily exposed populations. Fibrosis of the visceral pleura is much less common and it is not specifically related to asbestos. The incidence of asbestosis (pulmonary fibrosis induced by asbestos exposure) is diminishing in France. According to the data of the National Programme for the Surveillance of Mesothelioma, the annual number of cases of pleural mesothelioma varied from 646 to 800 for the period 1998-2003. Primary lung cancer due to asbestos does not have specific clinical, radiological or anatomical-pathological features. The number of cases attributable to asbestos has been estimated as between 2086 and 4172 for 1999. A report of the National Academy of Medicine, the Academy of Sciences and the International Centre of Cancer Research has calculated the incidence of primary lung cancer due to asbestos in 2000 as 969 for men and 133 for women. The risk of primary lung cancer is increased in populations exposed to asbestos even in the absence of radiological signs of pulmonary fibrosis. For an identical total exposure, asbestosis increases the risk of primary lung cancer. On the basis of radiological studies, pleural plaques are associated with an increased risk of lung cancer and mesothelioma. For identical levels of total asbestos exposure, it has not been established that the presence of pleural plaques increases the risk of developing thoracic cancer.}, } @article {pmid23094904, year = {2012}, author = {Oc, M and Oc, B and Dogan, R}, title = {Unexpected malignant pericardial mesothelioma presenting as pericardial constriction.}, journal = {Bratislavske lekarske listy}, volume = {113}, number = {10}, pages = {620-621}, doi = {10.4149/bll_2012_140}, pmid = {23094904}, issn = {0006-9248}, mesh = {Adult ; Cardiac Tamponade/*etiology ; Heart Neoplasms/complications/*diagnosis ; Humans ; Male ; Mesothelioma/complications/*diagnosis ; Pericardial Effusion/etiology ; *Pericardium ; }, abstract = {Pericardial mesothelioma is a rare and highly aggressive and lethal cardiac tumour. A 25-year-old male patient who was complaining of fever, night sweats, shortness of breath and palpitations after an upper respiratory system infection was admitted in May 2008. He had a history of 12 years exposure to asbestos. When the patient was referred to our hospital in June 2008, his complaints of palpitations and shortness of breath were continuing. He had oedema of legs and a venous swelling on his neck. The echocardiography showed pericardial effusion and pericardial thickening which were also found on the CT. Through median sternotomy a pericardectomy and tumor resection were performed. Histological and immunohistochemical findings lead to the diagnosis of malignant pericardial mesothelioma. In conclusion, there is still not a radical therapy for primary pericardial mesothelioma. Surgery is done to prevent cardiac tamponade and relieves constriction (Fig. 1, Ref. 12).}, } @article {pmid23093275, year = {2012}, author = {Park, EK and Wilson, D and Yates, DH}, title = {A predictive equation to adjust for clinical variables in soluble mesothelin-related protein (SMRP) levels.}, journal = {Clinical chemistry and laboratory medicine}, volume = {50}, number = {12}, pages = {2199-2204}, doi = {10.1515/cclm-2012-0314}, pmid = {23093275}, issn = {1437-4331}, mesh = {Aged ; Biomarkers, Tumor/*blood ; Female ; Humans ; Male ; Mesothelioma/blood/*diagnosis ; Middle Aged ; Multidrug Resistance-Associated Proteins/*blood ; Prospective Studies ; }, abstract = {BACKGROUND: Malignant mesothelioma (MM) is an aggressive pleural tumor which is difficult to diagnose in its early stages. Thus, biomarkers for MM including soluble mesothelin-related protein (SMRP) are currently an area of intense research interest. However, SMRP is affected by several factors other than malignancy which need to be taken into account in the individual patient. This study aimed to evaluate factors required to adjust SMRP levels for such variables and produce a useful prediction equation for clinical application.

METHODS: Serum SRMP levels were measured in 535 subjects formerly exposed to asbestos and silica, including many with asbestos-related disorders (ARDs). Linear regression analyses were used to quantify the strength and “ direction ” of the relationship between SMRP and several independent variables,and 2 × 2 tables were used to determine the diagnostic accuracy of SMRP levels, taking into account clinical variables.

RESULTS: SMRP levels were affected by age and glomerular filtration rate (GFR), which were strong confounders in this study. Body mass index (BMI) was also an initial confounder but lost significance after other factors were taken into account.SMRP was also affected by smoking. Poor sensitivity (15.1 %)for SMRP values among subjects with non-malignant asbestos-related disorders was found when compared to currently healthy subjects with a history of asbestos exposure.

CONCLUSIONS: The present study proposes an equation based on age and GFR to improve diagnostic accuracy of SMRP.The poor sensitivity of SMRP found in this study suggests that further work is needed to fi nd new candidate biomarkers for diagnosing early stage MM.}, } @article {pmid23085037, year = {2013}, author = {Kao, SC and Lee, K and Klebe, S and Henderson, D and McCaughan, B and Vardy, J and Clarke, S and van Zandwijk, N}, title = {Excision repair cross complementation group 1 and thymidylate synthase expression in patients with mesothelioma.}, journal = {Clinical lung cancer}, volume = {14}, number = {2}, pages = {164-171}, doi = {10.1016/j.cllc.2012.09.003}, pmid = {23085037}, issn = {1938-0690}, mesh = {Adult ; Aged ; DNA-Binding Proteins/*analysis ; Endonucleases/*analysis ; Female ; Humans ; Immunohistochemistry ; Male ; Mesothelioma/*chemistry/mortality/surgery ; Middle Aged ; Pleural Neoplasms/*chemistry/mortality/surgery ; Pneumonectomy ; Prognosis ; Thymidylate Synthase/*analysis ; }, abstract = {BACKGROUND: We hypothesized that in patients with malignant pleural mesothelioma (MPM) undergoing extrapleural pneumonectomy (EPP), high expression of excision repair cross complementation group 1 (ERCC1) and low expression of thymidylate synthase (TS) are associated with prolonged survival.

PATIENTS AND METHODS: Consecutive patients undergoing EPP at our institutions were reviewed. Tissue microarrays were constructed using five 1-mm cores per patient. TS and ERCC1 protein expression was evaluated by immunohistochemical techniques. The average percentage scores from evaluable cores were assessed and the median score was used to divide the group. Overall survival (OS) from the time of surgery was determined by the Kaplan-Meier method and results were compared by the log-rank test.

RESULTS: Eighty patients were included: median age, 58 years; 79% men; 76% epithelial and 24% biphasic subtypes; 25% and pathologic stage I/II and 73% stage III/IV. The median OS was 18.2 months (80% deceased at the censor date). Nineteen patients received neoadjuvant chemotherapy; 2 patients received chemotherapy with adjuvant intent and 28 patients received palliative chemotherapy. The median score was 10.2% for TS and 35% for ERCC1. There was no correlation between TS expression and OS (13.7 vs. 21.6 months for low and high levels, respectively; P = .32). There was a trend between high ERCC1 expression and longer OS (27.6 vs. 10.3 months; P = .06).

CONCLUSION: In this series of patients with MPM undergoing EPP, TS expression was not associated with prolonged survival, but there was a trend for longer survival in patients with high ERCC1 expression.}, } @article {pmid23077450, year = {2012}, author = {Kovac, V and Zwitter, M and Zagar, T}, title = {Improved survival after introduction of chemotherapy for malignant pleural mesothelioma in Slovenia: Population-based survey of 444 patients.}, journal = {Radiology and oncology}, volume = {46}, number = {2}, pages = {136-144}, pmid = {23077450}, issn = {1581-3207}, abstract = {BACKGROUND: Malignant pleural mesothelioma is a rare tumour with increasing frequency throughout the world. Due to long latency after exposure to asbestos, restrictions in the production and use of asbestos have not yet alleviated the burden of mesothelioma. During the last decade, several trials confirmed the benefit of systemic treatment with drugs such as doublets with cisplatina and gemcitabine or pemetrexed for carefully selected patients in good performance status. The purpose of this survey was to assess the impact of systemic treatment for the whole national population of patients with mesothelioma. PATIENTS AND METHODS.: A retrospective study included all patients in Slovenia with histologically confirmed diagnosis of malignant pleural mesothelioma in the period from 1974 till 2008. Data from the Cancer Registry of Slovenia were supplemented by review of clinical records of the Institute of Oncology in Ljubljana where virtually all non-surgical treatment for mesothelioma was performed. We analysed the incidence, treatment, and survival of patients treated in the era of infrequent chemotherapy (1974-2003, the first period) and after it (2004-2008, the second period).

RESULTS: The survey included 444 patients, of whom 325 and 119 were diagnosed in the first and second period, respectively. Joinpoint regression analysis showed that after 1995 the trend in crude incidence rates increased more rapidly; the annual change was 0.03 per 100,000 per year before 1995 and 0.06 per 100,000 per year after. There was clear male predominance (70%) throughout the period covered by the survey. The proportion of patients above 65 years of age increased from 41.8% to 54.6% for the first and second period, respectively (p = 0.02). With a total of 52 (11.7%) operated patients, surgical treatment was rare and used only for selected patients with early disease and without comorbidity, leading to their relatively long median survival of 13.6 months. Chemotherapy was applied to 56 (17.2%) and to 96 (80.7%) patients during the first and second period, respectively. While a variety of older drugs were used in the first period, the most common regimen in the second period (applied to 91 patients) was doublet of low-dose gemcitabine in prolonged infusion and cisplatin. For the whole population of patients regardless the mode of treatment, median survival was 7.4 and 12.6 months (p-value = 0.037) for the first and second period, respectively.

CONCLUSIONS: Increasing incidence, male predominance and increased proportion of older patients confirm that the burden of mesothelioma persists in spite of a 15-years old ban in the production of asbestos. Modern chemotherapy, and in particular treatment with low-dose gemcitabine in prolonged infusion and cisplatin significantly prolonged median survival of patients with malignant pleural mesothelioma in Slovenia.}, } @article {pmid23074975, year = {2012}, author = {Smith, DR and Beh, EJ}, title = {Asbestos kills: no matter how you cut the data.}, journal = {Archives of environmental & occupational health}, volume = {67}, number = {4}, pages = {187-188}, doi = {10.1080/19338244.2012.675791}, pmid = {23074975}, issn = {2154-4700}, mesh = {Air Pollutants, Occupational/*adverse effects ; Asbestos/*adverse effects ; Asbestosis/*mortality ; Carcinogens, Environmental/*adverse effects ; Humans ; Lung Neoplasms/etiology/mortality ; Mesothelioma/etiology/mortality ; Occupational Exposure/*adverse effects ; }, } @article {pmid23072703, year = {2013}, author = {Baud, M and Strano, S and Dechartres, A and Jouni, R and Triponez, F and Chouaid, C and Forgez, P and Damotte, D and Roche, N and Régnard, JF and Alifano, M}, title = {Outcome and prognostic factors of pleural mesothelioma after surgical diagnosis and/or pleurodesis.}, journal = {The Journal of thoracic and cardiovascular surgery}, volume = {145}, number = {5}, pages = {1305-1311}, doi = {10.1016/j.jtcvs.2012.09.023}, pmid = {23072703}, issn = {1097-685X}, mesh = {Age Factors ; Aged ; Aged, 80 and over ; Biomarkers/blood ; Biopsy ; C-Reactive Protein/analysis ; Female ; Humans ; Kaplan-Meier Estimate ; Leukocytosis/mortality ; Male ; Mesothelioma/mortality/pathology/surgery/*therapy ; Middle Aged ; Multivariate Analysis ; Pleural Neoplasms/mortality/pathology/surgery/*therapy ; *Pleurodesis/adverse effects/mortality ; Predictive Value of Tests ; Proportional Hazards Models ; Retrospective Studies ; Risk Assessment ; Risk Factors ; *Thoracic Surgery, Video-Assisted ; Time Factors ; Treatment Outcome ; }, abstract = {OBJECTIVE: The objective of this study was to evaluate long-term survival and prognostic factors in patients with malignant pleural mesothelioma.

METHODS: All consecutive patients referred for surgical diagnosis and/or pleurodesis for malignant pleural mesothelioma between 2000 and 2010 were studied. The following parameters were prospectively recorded: age, sex, tobacco consumption, asbestos exposure, type and duration of symptoms, American Society of Anesthesiologists (ASA) score, body mass index, preoperative C-reactive protein levels, white blood cells and platelet count, pachypleuritis on chest radiograph, type of diagnostic surgical procedure, histologic type, modality of pleurodesis, and chemotherapy. Survival was assessed on March 1, 2011.

RESULTS: A total of 170 patients were included. For the entire population, median survival was 12 months (95% confidence interval [CI], 10-15). Two-, 5-, and 7-year overall survival was 26% (95% CI, 19-35), 11% (95% CI, 6-21), and 5% (95% CI, 9-22), respectively. Asbestos exposure, age, ASA class III versus ASA classes I and II, nonepithelioid histology, C-reactive protein levels >3 mg/L, and white cell count >12,000/mm(3) influenced outcome in univariate analysis. Multivariate analysis showed that nonepithelioid histology (hazard ratio [HR], 2.76; 95% CI, 1.50-5.08); age (HR, 1.05; 95% CI, 1.01-1.08); C-reactive protein levels between 4 and 50 mg/L, and >51 (HR, 2.28; 95% CI, 1.18-4.42; and HR, 2.69; CI, 1.29-5.60, respectively); and leukocytosis >12,000/mm(3) (HR, 2.28; 95% CI, 1.22-4.25) were independent worse survival predictors.

CONCLUSIONS: Median survival in an unselected population of patients with malignant pleural mesothelioma treated nonsurgically is 12 months. Nonepithelioid histology, older age, abnormal C-reactive protein levels, and leukocytosis are independent predictors of worse survival.}, } @article {pmid23071320, year = {2012}, author = {Mazzoni, E and Corallini, A and Cristaudo, A and Taronna, A and Tassi, G and Manfrini, M and Comar, M and Bovenzi, M and Guaschino, R and Vaniglia, F and Magnani, C and Casali, F and Rezza, G and Barbanti-Brodano, G and Martini, F and Tognon, MG}, title = {High prevalence of serum antibodies reacting with simian virus 40 capsid protein mimotopes in patients affected by malignant pleural mesothelioma.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {109}, number = {44}, pages = {18066-18071}, pmid = {23071320}, issn = {1091-6490}, mesh = {Amino Acid Sequence ; Antibodies, Viral/*blood ; Capsid Proteins/chemistry/*immunology ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Male ; Mesothelioma/*immunology ; Molecular Sequence Data ; Pleural Neoplasms/*immunology ; Pregnancy ; Simian virus 40/*immunology ; }, abstract = {Human malignant pleural mesothelioma (MPM) is considered a rare tumor, but recent estimations indicate that one-quarter million people will die of this neoplasm in Europe in the next three decades. The mineral asbestos is considered the main causative agent of this neoplasm. MPM is largely unresponsive to conventional chemotherapy/radiotherapy. In addition to asbestos exposure, genetic predisposition to asbestos carcinogenesis and to simian virus (SV)40 infection has also been suggested. SV40 is a DNA tumor virus found in some studies to be associated at high prevalence with MPM. SV40 sequences have also been detected, although at a lower prevalence than in MPM, in blood specimens from healthy donors. However, some studies have failed to reveal SV40 footprints in MPM and its association with this neoplasm. These conflicting results indicate the need for further investigations with new approaches. We report on the presence of antibodies in serum samples from patients affected by MPM that specifically react with two different SV40 mimotopes. The two SV40 peptides used in indirect ELISAs correspond to viral capsid proteins. ELISA with the two SV40 mimotopes gave overlapping results. Our data indicate that in serum samples from MPM-affected patients (n = 97), the prevalence of antibodies against SV40 viral capsid protein antigens is significantly higher (26%, P = 0.043) than in the control group (15%) represented by healthy subjects (n = 168) with the same median age (66 y) and sex. Our results suggest that SV40 is associated with a subset of MPM and circulates in humans.}, } @article {pmid23056237, year = {2012}, author = {Ostroff, RM and Mehan, MR and Stewart, A and Ayers, D and Brody, EN and Williams, SA and Levin, S and Black, B and Harbut, M and Carbone, M and Goparaju, C and Pass, HI}, title = {Early detection of malignant pleural mesothelioma in asbestos-exposed individuals with a noninvasive proteomics-based surveillance tool.}, journal = {PloS one}, volume = {7}, number = {10}, pages = {e46091}, pmid = {23056237}, issn = {1932-6203}, support = {U01 CA111295/CA/NCI NIH HHS/United States ; 2U01CA111295-04/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos ; Biomarkers, Tumor/blood ; Carcinogens ; Case-Control Studies ; Cohort Studies ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Lectins/blood ; Male ; Mesothelioma/chemically induced/*diagnosis/metabolism ; Middle Aged ; Pleural Neoplasms/chemically induced/*diagnosis/metabolism ; Principal Component Analysis ; Proteomics/*methods ; Public Health Surveillance/*methods ; Reproducibility of Results ; Sensitivity and Specificity ; Young Adult ; Ficolins ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MM) is an aggressive, asbestos-related pulmonary cancer that is increasing in incidence. Because diagnosis is difficult and the disease is relatively rare, most patients present at a clinically advanced stage where possibility of cure is minimal. To improve surveillance and detection of MM in the high-risk population, we completed a series of clinical studies to develop a noninvasive test for early detection.

We conducted multi-center case-control studies in serum from 117 MM cases and 142 asbestos-exposed control individuals. Biomarker discovery, verification, and validation were performed using SOMAmer proteomic technology, which simultaneously measures over 1000 proteins in unfractionated biologic samples. Using univariate and multivariate approaches we discovered 64 candidate protein biomarkers and derived a 13-marker random forest classifier with an AUC of 0.99±0.01 in training, 0.98±0.04 in independent blinded verification and 0.95±0.04 in blinded validation studies. Sensitivity and specificity at our pre-specified decision threshold were 97%/92% in training and 90%/95% in blinded verification. This classifier accuracy was maintained in a second blinded validation set with a sensitivity/specificity of 90%/89% and combined accuracy of 92%. Sensitivity correlated with pathologic stage; 77% of Stage I, 93% of Stage II, 96% of Stage III and 96% of Stage IV cases were detected. An alternative decision threshold in the validation study yielding 98% specificity would still detect 60% of MM cases. In a paired sample set the classifier AUC of 0.99 and 91%/94% sensitivity/specificity was superior to that of mesothelin with an AUC of 0.82 and 66%/88% sensitivity/specificity. The candidate biomarker panel consists of both inflammatory and proliferative proteins, processes strongly associated with asbestos-induced malignancy.

SIGNIFICANCE: The SOMAmer biomarker panel discovered and validated in these studies provides a solid foundation for surveillance and diagnosis of MM in those at highest risk for this disease.}, } @article {pmid23055748, year = {2012}, author = {Zarogoulidis, P and Mavroudi, M and Porpodis, K and Domvri, K and Sakkas, A and Machairiotis, N and Stylianaki, A and Tsiotsios, A and Courcoutsakis, N and Zarogoulidis, K}, title = {Pegylated liposomal doxorubicin in malignant pleural mesothelioma: a possible guardian for long-term survival.}, journal = {OncoTargets and therapy}, volume = {5}, number = {}, pages = {231-236}, pmid = {23055748}, issn = {1178-6930}, abstract = {Malignant pleural mesothelioma is a rare and aggressive malignancy of the pleura correlated with exposure to asbestos, with a medium survival of 11-12 months after diagnosis. A case of a 67-year-old male who had previously worked in the asbestos industry and is a current smoker is reported. The computed tomography evaluation revealed a right pleural mass with pleural thickening, and the pleural biopsy confirmed a diagnosis of malignant pleural mesothelioma. He was treated with chemotherapy consisting of etoposide, paclitaxel, and pegylated liposomal doxorubicin hydrochloride. After completion of chemotherapy, radiologic evaluation confirmed a reduction of pleural thickening and improvement in his symptoms. A complete presentation of each drug formulation and characteristics are also included in this paper. The patient's follow-up is continuing, and computed tomography reveals stable disease 9 years after initial examination.}, } @article {pmid23052177, year = {2012}, author = {Mensi, C and Termine, L and Garberi, A and Meroni, S and Levi, D and Balzarini, L and Riboldi, L}, title = {Spinal cord compression: an unusual presentation of malignant pleural mesothelioma. A case report and review of the literature.}, journal = {Tumori}, volume = {98}, number = {4}, pages = {e92-7}, doi = {10.1700/1146.12651}, pmid = {23052177}, issn = {2038-2529}, mesh = {Aged ; Asbestos/*toxicity ; Back Pain/etiology ; Carcinogens/*toxicity ; Diagnosis, Differential ; Fatal Outcome ; Humans ; Leg ; Magnetic Resonance Imaging ; Male ; Mesothelioma/chemically induced/*complications/*diagnosis/therapy ; Muscle Weakness/etiology ; Occupational Exposure/*adverse effects ; Palliative Care/methods ; Paralysis/etiology ; Pleural Neoplasms/chemically induced/*complications/*diagnosis/therapy ; Spinal Cord Compression/complications/*etiology ; Thoracic Vertebrae ; Tomography, X-Ray Computed ; }, abstract = {Pleural malignant mesothelioma is a locally invasive tumor that tends to progress due to direct extension of the tumor into the pulmonary parenchyma, the chest wall, the mediastinum, or the abdominal cavity via the diaphragm. In the later stages of the disease, distant metastases can occur. Metastases to the nervous system are rare, and clinical signs of nervous system involvement typically appear between 2 months and 6 years after the primary diagnosis. However, the case presented here manifested as neurological impairment without any respiratory symptoms.}, } @article {pmid23050525, year = {2012}, author = {Pass, HI and Levin, SM and Harbut, MR and Melamed, J and Chiriboga, L and Donington, J and Huflejt, M and Carbone, M and Chia, D and Goodglick, L and Goodman, GE and Thornquist, MD and Liu, G and de Perrot, M and Tsao, MS and Goparaju, C}, title = {Fibulin-3 as a blood and effusion biomarker for pleural mesothelioma.}, journal = {The New England journal of medicine}, volume = {367}, number = {15}, pages = {1417-1427}, pmid = {23050525}, issn = {1533-4406}, support = {U01 CA111295/CA/NCI NIH HHS/United States ; U01 CA113913/CA/NCI NIH HHS/United States ; U01 CA-113913/CA/NCI NIH HHS/United States ; U01 CA-111295/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; *Asbestos/adverse effects ; Biomarkers/blood ; Case-Control Studies ; Diagnosis, Differential ; Extracellular Matrix Proteins/*blood ; Female ; Humans ; Kaplan-Meier Estimate ; Male ; Mesothelioma/blood/*diagnosis ; Middle Aged ; *Occupational Exposure ; Pleural Effusion/blood/diagnosis ; Pleural Effusion, Malignant/blood/diagnosis ; Pleural Neoplasms/blood/*diagnosis ; ROC Curve ; Sensitivity and Specificity ; }, abstract = {BACKGROUND: New biomarkers are needed to detect pleural mesothelioma at an earlier stage and to individualize treatment strategies. We investigated whether fibulin-3 in plasma and pleural effusions could meet sensitivity and specificity criteria for a robust biomarker.

METHODS: We measured fibulin-3 levels in plasma (from 92 patients with mesothelioma, 136 asbestos-exposed persons without cancer, 93 patients with effusions not due to mesothelioma, and 43 healthy controls), effusions (from 74 patients with mesothelioma, 39 with benign effusions, and 54 with malignant effusions not due to mesothelioma), or both. A blinded validation was subsequently performed. Tumor tissue was examined for fibulin-3 by immunohistochemical analysis, and levels of fibulin-3 in plasma and effusions were measured with an enzyme-linked immunosorbent assay.

RESULTS: Plasma fibulin-3 levels did not vary according to age, sex, duration of asbestos exposure, or degree of radiographic changes and were significantly higher in patients with pleural mesothelioma (105±7 ng per milliliter in the Detroit cohort and 113±8 ng per milliliter in the New York cohort) than in asbestos-exposed persons without mesothelioma (14±1 ng per milliliter and 24±1 ng per milliliter, respectively; P<0.001). Effusion fibulin-3 levels were significantly higher in patients with pleural mesothelioma (694±37 ng per milliliter in the Detroit cohort and 636±92 ng per milliliter in the New York cohort) than in patients with effusions not due to mesothelioma (212±25 and 151±23 ng per milliliter, respectively; P<0.001). Fibulin-3 preferentially stained tumor cells in 26 of 26 samples. In an overall comparison of patients with and those without mesothelioma, the receiver-operating-characteristic curve for plasma fibulin-3 levels had a sensitivity of 96.7% and a specificity of 95.5% at a cutoff value of 52.8 ng of fibulin-3 per milliliter. In a comparison of patients with early-stage mesothelioma with asbestos-exposed persons, the sensitivity was 100% and the specificity was 94.1% at a cutoff value of 46.0 ng of fibulin-3 per milliliter. Blinded validation revealed an area under the curve of 0.87 for plasma specimens from 96 asbestos-exposed persons as compared with 48 patients with mesothelioma.

CONCLUSIONS: Plasma fibulin-3 levels can distinguish healthy persons with exposure to asbestos from patients with mesothelioma. In conjunction with effusion fibulin-3 levels, plasma fibulin-3 levels can further differentiate mesothelioma effusions from other malignant and benign effusions. (Funded by the Early Detection Research Network, National Institutes of Health, and others.).}, } @article {pmid23045294, year = {2013}, author = {Watzka, SB and Posch, F and Pass, HI and Flores, RM and Hannigan, GE and Bernhard, D and Weber, M and Mueller, MR}, title = {Serum concentration of integrin-linked kinase in malignant pleural mesothelioma and after asbestos exposure.}, journal = {European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery}, volume = {43}, number = {5}, pages = {940-945}, pmid = {23045294}, issn = {1873-734X}, support = {2U01CA111295-04/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Air Pollutants, Occupational/analysis/*blood/poisoning ; Analysis of Variance ; Asbestos/*poisoning ; Case-Control Studies ; Diagnosis, Differential ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Male ; Mesothelioma/blood/*enzymology/etiology ; Middle Aged ; Occupational Exposure/*analysis ; Pleural Neoplasms/blood/*enzymology/etiology ; Protein Serine-Threonine Kinases/*blood ; ROC Curve ; Sensitivity and Specificity ; }, abstract = {OBJECTIVES: Integrin-linked kinase (ILK) is an intracellular protein implicated in chronic inflammation and neoplastic transformation. In a recently accomplished pilot study, we showed that ILK can be detected in the serum of patients with benign and malignant chest diseases, including malignant pleural mesothelioma (MPM). Interestingly, average serum ILK concentrations were 10 times higher in MPM patients when compared with the rest of the study population, and a diagnostic test solely based on serum ILK concentration could discriminate between MPM and non-MPM with considerable accuracy. This study aimed to investigate whether serum ILK concentration could also be used to discriminate between MPM and asbestos exposure only.

METHODS: Using a self-developed sandwich enzyme-linked immunosorbent assay, we measured serum ILK concentrations in 101 MPM patients, and 96 asbestos-exposed, but healthy insulation workers. Seventy-three MPM patients had an epitheloid subtype (72.3%), and 42 had a Stage I or II disease (41.6%).

RESULTS: When compared with asbestos-exposed individuals, MPM patients of all clinical stages had significantly higher (mean ± standard deviation, median) serum ILK concentrations (10.7 ± 13.6, median 7 ng/ml vs 3.1 ± 4.6, median 1.4 ng/ml; P < 0.001). Among MPM patients, the serum ILK concentration was significantly higher at advanced disease stages III + IV than at early stages I + II (13.7 ± 15.9, median 8.5 ng/ml vs 6.7 ± 7.8, median 3.5 ng/ml; P = 0.02). Using serum ILK to discriminate between MPM patients and asbestos-exposed individuals yielded an area under the curve of 0.69 (95% confidence interval 0.63-0.76). The corresponding sensitivity and specificity for a cut-off of 4.49 ng/ml ILK are 61.4 and 80.2%, respectively.

CONCLUSIONS: These data show significant differences between MPM patients and asbestos-exposed but healthy individuals concerning their serum ILK concentration. Furthermore, since ILK levels are increased in advanced MPM stages in comparison with early MPM stages, we suggest evaluating its potential use as a marker of disease progression in MPM.}, } @article {pmid23034792, year = {2012}, author = {Darnton, A and Hodgson, J and Benson, P and Coggon, D}, title = {Mortality from asbestosis and mesothelioma in Britain by birth cohort.}, journal = {Occupational medicine (Oxford, England)}, volume = {62}, number = {7}, pages = {549-552}, pmid = {23034792}, issn = {1471-8405}, support = {MC_UP_A620_1018/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Asbestosis/*mortality/physiopathology/prevention & control ; Carcinogens ; Construction Materials/adverse effects ; Death Certificates ; Disease Progression ; Humans ; Lung Neoplasms/*mortality/physiopathology/prevention & control ; Male ; Mesothelioma/*mortality/physiopathology/prevention & control ; Middle Aged ; Occupational Diseases/chemically induced/*mortality/prevention & control ; Occupational Exposure/prevention & control/*statistics & numerical data ; Prevalence ; Registries ; United Kingdom/epidemiology ; }, abstract = {BACKGROUND: Analysis of occupational mortality in England and Wales during 1991-2000 showed no decline in work-attributable deaths from asbestosis.

AIMS: To explore why there was no decline in mortality from asbestosis despite stricter controls on asbestos exposure over recent decades.

METHODS: Using data from registers of all deaths in Great Britain with mention of mesothelioma or asbestosis on the death certificate, we plotted death rates by 5 year age group within 5 year birth cohorts for(a) mesothelioma and (b) asbestosis without mention of mesothelioma.

RESULTS: Analysis was based on a total of 33,751 deaths from mesothelioma and 5396 deaths from asbestosis. For both diseases, mortality showed a clear cohort effect; within birth cohorts, death rates increased progressively with age through to 85 years and older. However, highest mortality from mesothelioma was in men born during 1939-43, whereas, mortality from asbestosis peaked in men born during 1924-38.

CONCLUSIONS: Our findings suggest that mortality, in Britain, from asbestosis has been determined mainly by cumulative exposure to asbestos before 45 years of age and that the effect of such exposure continues through to old age. That mortality from asbestosis peaked in earlier birth cohorts than mortality from mesothelioma may reflect a difference in exposure-response relationships for the two diseases. The discrepancy could be explained if risk of asbestosis increased more steeply than that of mesothelioma at higher levels of exposure to asbestos and if the highest prevalence of heavy exposure occurred in earlier birth cohorts than the highest prevalence of less intense exposures.}, } @article {pmid23031505, year = {2012}, author = {Girardelli, M and Maestri, I and Rinaldi, RR and Tognon, M and Boldorini, R and Bovenzi, M and Crovella, S and Comar, M}, title = {NLRP1 polymorphisms in patients with asbestos-associated mesothelioma.}, journal = {Infectious agents and cancer}, volume = {7}, number = {1}, pages = {25}, pmid = {23031505}, issn = {1750-9378}, abstract = {BACKGROUND: An increasing incidence of malignant mesothelioma (MM) cases in patients with low levels of asbestos exposure suggests the interference of alternative cofactors. SV40 infection was detected, as co-morbidity factor, only in 22% of asbestos-MM patients from a North-Eastern Italy area. An additional mechanism of injury related to asbestos exposure in MM development has been recently associated to inflammatory responses, principally driven by interleukin (IL)-1 beta (ß) activated within the inflammasome complex.NLRP3 inflammosome has been described as the intracellular sensor for asbestos able to induce inflammasome activation and IL-1ß secretion while NLRP1 is expressed in lung epithelial cells and alveolar macrophages and contributes to the immune response and to survival/apoptosis balance. This study proposes to evaluate the impact of known NLRP3 and NLRP1 polymorphisms in the individual susceptibility to asbestos-induced mesothelioma in subjects from a hyperendemic area for MM.

METHODS: 134 Italian patients with diagnosis of mesothelioma due (MMAE, n=69) or not (MMAF, n=65) to asbestos, 256 healthy Italian blood donors and 101 Italian healthy subjects exposed to asbestos (HCAE) were genotyped for NLRP1 (rs2670660 and rs12150220) and NLRP3 (rs35829419 and rs10754558) polymorphisms.

RESULTS: While NLRP3 SNPs were not associated to mesothelioma, the NLRP1 rs12150220 allele T was significantly more frequent in MMAE (0.55) than in HCAE (0.41) (p=0.011; OR=1.79) suggesting a predisponent effect of this allele on the development of mesothelioma. This effect was amplified when the NLRP1 rs2670660 allele was combined with the NLRP1 rs12150220 allele (p=0.004; OR=0.52).

CONCLUSION: Although NLRP3 SNPs was not involved in mesothelioma predisposition, these data proposed NLRP1 as a novel factor possibly involved in the development of mesothelioma.}, } @article {pmid23026008, year = {2012}, author = {Courtice, MN and Lin, S and Wang, X}, title = {An updated review on asbestos and related diseases in China.}, journal = {International journal of occupational and environmental health}, volume = {18}, number = {3}, pages = {247-253}, doi = {10.1179/1077352512Z.00000000021}, pmid = {23026008}, issn = {1077-3525}, mesh = {Asbestos/*toxicity ; Asbestosis/*epidemiology/etiology/mortality/prevention & control ; China/epidemiology ; Humans ; Incidence ; Industry ; Lung Neoplasms/chemically induced/*epidemiology/mortality/prevention & control ; Mesothelioma/*epidemiology/etiology/mortality/prevention & control ; *Occupational Exposure ; Prevalence ; }, abstract = {BACKGROUND: Asbestos is an industrial mineral that can cause diseases such as asbestosis, lung cancer, and mesothelioma. Asbestos consumption in China has increased steadily since the 1960s and is currently at half a million tonnes per year. Work conditions in the asbestos-related industries are poor and exposure levels frequently exceed the occupational exposure limit.

OBJECTIVE: To provide an updated overview on asbestos production and consumption in China and discuss what is known about the resulting burden of asbestos-related diseases.

FINDINGS: China is the world's top chrysotile consumer and second largest producer. Over a million people may be occupationally exposed, yet reliable disease statistics are unavailable and the national burden of asbestos-related disease (ARD) is not well known. Nevertheless, ARD prevalence, incidence, and mortality are expected to be high and will increase for many decades due to the volume of asbestos consumed historically, and a long latency period.

CONCLUSIONS: Government policies to prevent ARD have been implemented but more actions are necessary to ensure compliance and ultimately, the complete elimination of asbestos to prevent a heavy future disease burden.}, } @article {pmid23026002, year = {2012}, author = {Frank, AL}, title = {China and the US: asbestos in common.}, journal = {International journal of occupational and environmental health}, volume = {18}, number = {3}, pages = {179-180}, doi = {10.1179/1077352512Z.00000000032}, pmid = {23026002}, issn = {1077-3525}, mesh = {Asbestos/*toxicity ; Asbestosis/*epidemiology ; Humans ; Lung Neoplasms/*epidemiology ; Mesothelioma/*epidemiology ; *Occupational Exposure ; }, } @article {pmid23022841, year = {2011}, author = {Skammeritz, E and Omland, LH and Johansen, JP and Omland, O}, title = {Asbestos exposure and survival in malignant mesothelioma: a description of 122 consecutive cases at an occupational clinic.}, journal = {The international journal of occupational and environmental medicine}, volume = {2}, number = {4}, pages = {224-236}, pmid = {23022841}, issn = {2008-6520}, mesh = {Aged ; Asbestos/*toxicity ; Denmark/epidemiology ; Female ; Humans ; Incidence ; Male ; Mesothelioma/*epidemiology ; Occupational Diseases/*epidemiology ; Occupational Exposure/adverse effects/*statistics & numerical data ; Occupations ; Pleural Neoplasms/*epidemiology ; Prognosis ; Proportional Hazards Models ; Risk Factors ; Sex Factors ; Survival Rate ; }, abstract = {BACKGROUND: The natural history and etiology of malignant mesothelioma (MM) is already thoroughly described in the literature, but there is still debate on prognostic factors, and details of asbestos exposure and possible context with clinical and demographic data, have not been investigated comprehensively.

OBJECTIVE: Description of patients with MM, focusing on exposure, occupation, survival and prognostic factors.

METHODS: Review of medical records of patients with MM from 1984 to 2010 from a Danish Occupational clinic. Survival was estimated using Kaplan-Meier survival analysis and prognostic factors were identified by Cox regression analysis.

RESULTS: 110 (90.2%) patients were male, and 12 (9.8%) were female. The median (interquartile rang [IQR]) age was 65 (13) years. Pleural MM was seen in 101 (82.8%) patients, and peritoneal in 11 (9.0%); two (1.6%) had MM to tunica vaginalis testis, and eight (6.6%) to multiple serosal surfaces. We found 68 (55.7%) epithelial tumors, 26 (21.3%) biphasic, and 6 (4.9%) sarcomatoid. 12 (9.8%) patients received tri-modal therapy, 66 (54.1%) received one-/two-modality treatment, and 36 (29.5%) received palliative care. Asbestos exposure was confirmed in 107 (91.0%) patients, probable in four (3.3%), and unidentifiable in 11 (9.0%). The median (IQR) latency was 42 (12.5) years. Exposure predominantly occurred in shipyards. The median overall survival was 1.05 (95% CI: 0.96-1.39) years; 5-year survival was 5.0% (95% CI: 2.0%-13.0%). Female sex, good WHO performance status (PS), epithelial histology and tri-modal treatment were associated with a favorable prognosis.

CONCLUSION: MM continuously presents a difficult task diagnostically and therapeutically, and challenges occupational physicians with regard to identification and characterization of asbestos exposure.}, } @article {pmid23018647, year = {2013}, author = {Cunniff, B and Benson, K and Stumpff, J and Newick, K and Held, P and Taatjes, D and Joseph, J and Kalyanaraman, B and Heintz, NH}, title = {Mitochondrial-targeted nitroxides disrupt mitochondrial architecture and inhibit expression of peroxiredoxin 3 and FOXM1 in malignant mesothelioma cells.}, journal = {Journal of cellular physiology}, volume = {228}, number = {4}, pages = {835-845}, pmid = {23018647}, issn = {1097-4652}, support = {R01 CA152810/CA/NCI NIH HHS/United States ; T32 ES007122/ES/NIEHS NIH HHS/United States ; T32 ES007122-29/ES/NIEHS NIH HHS/United States ; }, mesh = {Adenosine Triphosphate/metabolism ; Cell Line, Tumor ; Cell Survival/drug effects/genetics ; Cytoplasm/drug effects/genetics/metabolism/physiology ; Forkhead Box Protein M1 ; Forkhead Transcription Factors/*antagonists & inhibitors/*biosynthesis/genetics/metabolism ; Homeostasis/drug effects/genetics/physiology ; Humans ; Mesothelioma/*metabolism/pathology ; Mitochondria/drug effects/*metabolism ; Mitochondrial Dynamics/drug effects/genetics/physiology ; Organophosphorus Compounds/pharmacology ; Oxidants/*metabolism ; Oxidation-Reduction/drug effects ; Peroxiredoxin III/*antagonists & inhibitors/*biosynthesis/genetics/metabolism ; Quinazolinones/pharmacology ; }, abstract = {Malignant mesothelioma (MM) is an intractable tumor of the peritoneal and pleural cavities primarily linked to exposure to asbestos. Recently, we described an interplay between mitochondrial-derived oxidants and expression of FOXM1, a redox-responsive transcription factor that has emerged as a promising therapeutic target in solid malignancies. Here we have investigated the effects of nitroxides targeted to mitochondria via triphenylphosphonium (TPP) moieties on mitochondrial oxidant production, expression of FOXM1 and peroxiredoxin 3 (PRX3), and cell viability in MM cells in culture. Both Mito-carboxy-proxyl (MCP) and Mito-TEMPOL (MT) caused dose-dependent increases in mitochondrial oxidant production that was accompanied by inhibition of expression of FOXM1 and PRX3 and loss of cell viability. At equivalent concentrations TPP, CP, and TEMPOL had no effect on these endpoints. Live cell ratiometric imaging with a redox-responsive green fluorescent protein targeted to mitochondria (mito-roGFP) showed that MCP and MT, but not CP, TEMPOL, or TPP, rapidly induced mitochondrial fragmentation and swelling, morphological transitions that were associated with diminished ATP levels and increased production of mitochondrial oxidants. Mdivi-1, an inhibitor of mitochondrial fission, did not rescue mitochondria from fragmentation by MCP. Immunofluorescence microscopy experiments indicate a fraction of FOXM1 coexists in the cytoplasm with mitochondrial PRX3. Our results indicate that MCP and MT inhibit FOXM1 expression and MM tumor cell viability via perturbations in redox homeostasis caused by marked disruption of mitochondrial architecture, and suggest that both compounds, either alone or in combination with thiostrepton or other agents, may provide credible therapeutic options for the management of MM.}, } @article {pmid23010873, year = {2012}, author = {Chow, MT and Tschopp, J and Möller, A and Smyth, MJ}, title = {NLRP3 promotes inflammation-induced skin cancer but is dispensable for asbestos-induced mesothelioma.}, journal = {Immunology and cell biology}, volume = {90}, number = {10}, pages = {983-986}, doi = {10.1038/icb.2012.46}, pmid = {23010873}, issn = {1440-1711}, support = {09-0676/AICR_/Worldwide Cancer Research/United Kingdom ; }, mesh = {Animals ; Asbestos/adverse effects ; Carrier Proteins/genetics/immunology/*metabolism ; Cell Movement/genetics ; Cell Transformation, Neoplastic/genetics/immunology ; Disease Models, Animal ; Environmental Exposure/adverse effects ; Female ; Humans ; Inflammation/complications ; Interleukin-1beta/metabolism ; Mesothelioma/etiology/*immunology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Knockout ; NLR Family, Pyrin Domain-Containing 3 Protein ; Papilloma/chemically induced/*immunology ; Peritoneum/immunology/pathology ; Pleural Neoplasms/etiology/*immunology ; Skin Neoplasms/chemically induced/*immunology ; }, abstract = {Asbestos exposure can result in serious and frequently lethal diseases, including malignant mesothelioma. The host sensor for asbestos-induced inflammation is the NLRP3 inflammasome and it is widely assumed that this complex is essential for asbestos-induced cancers. Here, we report that acute interleukin-1β production and recruitment of immune cells into peritoneal cavity were significantly decreased in the NLRP3-deficient mice after the administration of asbestos. However, NLRP3-deficient mice displayed a similar incidence of malignant mesothelioma and survival times as wild-type mice. Thus, early inflammatory reactions triggered by asbestos are NLRP3-dependent, but NLRP3 is not critical in the chronic development of asbestos-induced mesothelioma. Notably, in a two-stage carcinogenesis-induced papilloma model, NLRP3-deficient mice showed a resistance phenotype in two different strain backgrounds, suggesting a tumour-promoting role of NLRP3 in certain chemically-induced cancer types.}, } @article {pmid23008275, year = {2013}, author = {Huang, CC and Michael, CW}, title = {Deciduoid mesothelioma: cytologic presentation and diagnostic pitfalls.}, journal = {Diagnostic cytopathology}, volume = {41}, number = {7}, pages = {629-635}, doi = {10.1002/dc.22902}, pmid = {23008275}, issn = {1097-0339}, mesh = {Abdominal Neoplasms/*pathology/therapy ; Adolescent ; Antineoplastic Agents/therapeutic use ; Cell Nucleus/pathology ; Fatal Outcome ; Female ; Humans ; Male ; Mesothelioma/*pathology/therapy ; Middle Aged ; Palliative Care ; }, abstract = {We report two cases of malignant deciduoid mesothelioma (MDM), a very rare variant of malignant mesothelioma (MM). Case 1: An 18-year-old male with no history of asbestos exposure presented with worsening abdominal pain, anorexia, and vomiting after a motor vehicle accident. A CT scan showed small amount of ascites and abdominal mass. An exploratory laparotomy revealed multiple yellow tan, firm nodules on the peritoneum and omentum. He received palliative treatment and died 5 months after the diagnosis. Case 2: A 64-year-old female with history of asbestos exposure initially presented with abdominal distension. CT scan showed abdominal mass with a large amount of ascites. A diagnostic laparoscopy revealed multiple peritoneal nodules. She underwent several regimens of chemotherapy over a period of 69 months and is still alive to date. In both cases, features of mesothelial origin were subtle and the smears showed predominantly single cells with marked nuclear atypia. The second case also contained few two-dimensional loose cell clusters with scalloped or hobnail borders. The clusters often exhibited a pseudoacinar structure surrounding a globular extracellular material. Groups of three to four cells often formed doublets and triplets with cell-to-cell windows. Our results show that MDM may not present with the traditional cytological features described in MM and can manifest with more nuclear pleomorphism resulting in erroneous diagnosis. Recognition of the subtle mesothelial features along with the appropriate ancillary tests is essential for accurate diagnosis.}, } @article {pmid23007055, year = {2012}, author = {Fazzo, L and Minelli, G and De Santis, M and Bruno, C and Zona, A and Marinaccio, A and Conti, S and Pirastu, R and Comba, P}, title = {Mesothelioma mortality surveillance and asbestos exposure tracking in Italy.}, journal = {Annali dell'Istituto superiore di sanita}, volume = {48}, number = {3}, pages = {300-310}, doi = {10.4415/ANN_12_03_11}, pmid = {23007055}, issn = {2384-8553}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Cluster Analysis ; Databases, Factual ; Environmental Restoration and Remediation ; Female ; Humans ; Industry ; International Classification of Diseases ; Italy/epidemiology ; Male ; Mesothelioma/*mortality ; Middle Aged ; Occupational Exposure/*statistics & numerical data ; }, abstract = {INTRODUCTION: Spatial distribution of mortality from pleural mesothelioma (which in the ICD-10 Revision has a specific code: C45.0) in Italy for the period 2003-2009 is described. Previous mortality studies at national level employed the topographic code "Malignant neoplasms of pleura", because of unavailability of a specific code in ICD-9 Revision for pleural mesothelioma.

METHODS: Standardized mortality ratios were computed for all municipalities, using each regional population as reference; for municipalities in Regions with rate higher than the national rate, the latter has been used as reference. SMRs were computed specifically also for each Italian Polluted Sites "of national concern for environmental remediation" (IPS) with asbestos exposure sources, composed by one or more municipalities, using regional rate as reference. Spatial Scan Statistics procedure, using SatScan software, was applied in cluster analysis: the country was divided into geographic macro-areas and the relative risks (RR) express the ratio of risk within the cluster to the risk of the macro-area outside the cluster. Clusters with p-value < 0.10 were selected.

RESULTS: The national standardized annual mortality rate was 1.7 cases per 100 000. Several areas with evident burden of asbestos-related disease were detected. Significant clusters were found in correspondence to asbestos-cement industries (e.g. Casale Monferrato, women: RR = 28.7), shipyards (e.g. Trieste, men: RR = 4.8), petrochemical industries (e.g. Priolo, men: RR = 6.9) and a stone quarry contaminated by fluoro-edenite fibres (Biancavilla, women: RR = 25.9). Some of the increased clusters correspond to IPS.

CONCLUSIONS: The results may contribute to detect asbestos exposure and to set priorites for environmental remediation.}, } @article {pmid23005599, year = {2012}, author = {Saito, R and Kasajima, A and Taniuchi, S and Fujishima, F and Ishida, K and Nakamura, Y and Yamanda, S and Takahashi, T and Hitomi, H and Murakami, K and Watanabe, M and Sasano, H}, title = {Case reports of primary pulmonary adenocarcinoma with pleural spread: so-called pseudomesotheliomatous adenocarcinoma.}, journal = {Pathology international}, volume = {62}, number = {10}, pages = {709-715}, doi = {10.1111/j.1440-1827.2012.02860.x}, pmid = {23005599}, issn = {1440-1827}, mesh = {Adenocarcinoma/metabolism/*pathology ; Aged ; Asbestos/adverse effects ; Biomarkers, Tumor/*analysis ; Diagnosis, Differential ; Diaphragm/pathology ; Fatal Outcome ; Humans ; Immunohistochemistry ; Lung/metabolism/pathology ; Lung Neoplasms/metabolism/*pathology ; Male ; Mesothelioma/metabolism/*pathology ; Middle Aged ; Pleura/metabolism/pathology ; Pleural Neoplasms/metabolism/*pathology ; Thoracic Wall/pathology ; }, abstract = {We report two autopsy cases of primary pulmonary adenocarcinoma associated with unusual pleural spread. Both patients had confirmed history of asbestos exposure. In the first patient the tumor was localized in one pulmonary lobe with marked infiltration into pleura, chest wall and diaphragm. In the second patient the entire right lung was covered by irregularly thickened tumor. Both tumors were mainly located in the extrapulmonary area and the intrapulmonary portions represented only minor components. Histologically, tumor cells demonstrated glandular and papillary growth patterns associated with focal hobnail-like features. Immunohistochemical evaluation revealed diffuse and marked immunoreactivity of TTF-1, CEA, CD15 and MOC31 in both cases, while calretinin, CK5/6, vimentin, thrombomodulin and HBME-1 were broadly positive in one case. D2-40 was not detected in either case. Examination using electron microscopy revealed the presence of sparse and short microvilli in tumor cells. All of the above findings are consistent with adenocarcinoma of the lung. Primary adenocarcinoma with a characteristic pleural extention grossly resembling malignant mesothelioma has been previously reported in the literature as pseudomesotheliomatous adenocarcinoma. This is the first report of pseudomesotheliomatous adenocarcinoma displaying variable immunoprofile with a diagnosis using electron microscopical examination. Additionally, we performed quantitative analysis of asbestos bodies in pseudomesotheliomatous adenocarcinoma.}, } @article {pmid23002275, year = {2012}, author = {Lenters, V and Burdorf, A and Vermeulen, R and Stayner, L and Heederik, D}, title = {Quality of evidence must guide risk assessment of asbestos.}, journal = {The Annals of occupational hygiene}, volume = {56}, number = {8}, pages = {879-887}, doi = {10.1093/annhyg/mes065}, pmid = {23002275}, issn = {1475-3162}, mesh = {Adult ; *Asbestos/adverse effects ; Asbestos, Amphibole/adverse effects ; Asbestos, Serpentine/adverse effects ; Humans ; Lung Neoplasms/chemically induced ; Mesothelioma/*chemically induced ; Occupational Exposure/adverse effects/statistics & numerical data ; Research/*standards ; Risk Assessment/*standards ; }, abstract = {In 2011, we reported on the sensitivity of lung cancer potency estimates for asbestos to the quality of the exposure assessment component of underlying evidence. Both this meta-analysis and a separate reassessment of standards published by the Health Council of the Netherlands (Gezondheidsraad) have been commented on by Berman and Case. A criticism is that we used a truncated data set. We incrementally excluded poorer-quality studies to evaluate trends in meta-analyzed lung cancer potency estimates (meta-K (L) values). This was one of three analysis approaches we presented. The other two used the full set of studies: a meta-analysis stratified by covariates and dichotomized by poorer and better exposure assessment aspects; and a meta-regression modeling both asbestos fiber type and these covariates. They also state that our results are not robust to removal of one study. We disagree with this claim and present additional sensitivity analyses underpinning our earlier conclusion that inclusion of studies with higher-quality asbestos-exposure assessment yield higher meta-estimates of the lung cancer risk per unit of exposure. We reiterate that potency differences for predominantly chrysotile- versus amphibole-asbestos-exposed cohorts are difficult to ascertain when meta-analyses are restricted to studies with fewer exposure assessment limitations. We strongly argue that the existence of any uncertainty related to potency issues should not hamper the development of appropriate evidence-based guidelines and stringent policies in order to protect the public from hazardous environmental and occupational exposures.}, } @article {pmid22986930, year = {2013}, author = {Ambrosini, GL and Bremner, AP and Reid, A and Mackerras, D and Alfonso, H and Olsen, NJ and Musk, AW and de Klerk, NH}, title = {No dose-dependent increase in fracture risk after long-term exposure to high doses of retinol or beta-carotene.}, journal = {Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA}, volume = {24}, number = {4}, pages = {1285-1293}, pmid = {22986930}, issn = {1433-2965}, mesh = {Adult ; Aged ; Dietary Supplements/*adverse effects ; Diterpenes ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Female ; Follow-Up Studies ; Humans ; Incidence ; Lung Neoplasms/prevention & control ; Male ; Mesothelioma/prevention & control ; Middle Aged ; Occupational Diseases/prevention & control ; Osteoporotic Fractures/*chemically induced/epidemiology/prevention & control ; Retinyl Esters ; Risk Assessment/methods ; Vitamin A/administration & dosage/adverse effects/*analogs & derivatives/therapeutic use ; Western Australia/epidemiology ; beta Carotene/administration & dosage/*adverse effects/therapeutic use ; }, abstract = {UNLABELLED: Uncertainty remains over whether or not high intakes of retinol or vitamin A consumed through food or supplements may increase fracture risk. This intervention study found no increase in fracture risk among 2,322 adults who took a controlled, high-dose retinol supplement (25,000 IU retinyl palmitate/day) for as long as 16 years. There was some evidence that beta-carotene supplementation decreased fracture risk in men.

INTRODUCTION: There is conflicting epidemiological evidence regarding high intakes of dietary or supplemental retinol and an increased risk for bone fracture. We examined fracture risk in a study administering high doses of retinol and beta-carotene (BC) between 1990 and 2007.

METHODS: The Vitamin A Program was designed to test the efficacy of retinol and BC supplements in preventing malignancies in persons previously exposed to blue asbestos. Participants were initially randomised to 7.5 mg retinol equivalents (RE)/day as retinyl palmitate, 30 mg/day BC or 0.75 mg/day BC from 1990 to 1996; after which, all participants received 7.5 mg RE/day. Fractures were identified by questionnaire and hospital admission data up until 2006. Risk of any fracture or osteoporotic fracture according to cumulative dose of retinol and BC supplementation was examined using conditional logistic regression models adjusting for age, sex, smoking, body mass index, medication use and previous fracture.

RESULTS: Supplementation periods ranged from 1 to 16 years. Of the 2,322 (664 females and 1,658 males) participants, 187 experienced 237 fractures. No associations were observed between cumulative dose of retinol and risk for any fracture (OR per 10 g RE=0.83; 95% CI, 0.63-1.08) or osteoporotic fracture (OR per 10 g RE=0.95; 95% CI 0.64-1.40). Among men, cumulative dose of BC was associated with a slightly reduced risk of any fracture (OR per 10 g=0.89; 95% CI 0.81-0.98) and osteoporotic fracture (OR per 10 g=0.84; 95% CI 0.72-0.97).

CONCLUSIONS: This study observed no increases in fracture risk after long-term supplementation with high doses of retinol and/or beta-carotene.}, } @article {pmid22974770, year = {2013}, author = {Finley, BL and Pierce, JS and Paustenbach, DJ and Galbraith, DA}, title = {Response to a letter to the editor by Dr. Murray M. Finkelstein regarding the article by Finley et al. (2012).}, journal = {Regulatory toxicology and pharmacology : RTP}, volume = {65}, number = {1}, pages = {180-181}, doi = {10.1016/j.yrtph.2012.08.019}, pmid = {22974770}, issn = {1096-0295}, mesh = {Asbestos, Serpentine/*adverse effects ; Female ; Humans ; Male ; Mesothelioma/*epidemiology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*epidemiology ; *Work ; }, } @article {pmid22961710, year = {2013}, author = {Sugalski, A and Davis, M and Prasannan, L and Saldivar, V and Hung, JY and Tomlinson, GE}, title = {Clinical, histologic, and genetic features of mesothelioma in a 7-year-old child.}, journal = {Pediatric blood & cancer}, volume = {60}, number = {1}, pages = {146-148}, doi = {10.1002/pbc.24284}, pmid = {22961710}, issn = {1545-5017}, mesh = {CA-125 Antigen/blood ; Child ; Chromosomes, Human, Pair 11 ; Comparative Genomic Hybridization ; Humans ; Immunohistochemistry ; Male ; Mesothelioma/*diagnosis/*genetics/pathology/therapy ; Peritoneal Neoplasms/*diagnosis/*genetics/pathology/therapy ; }, abstract = {Malignant mesothelioma (MM) is a highly aggressive malignancy that is extremely rare in children. This case report documents a 7-year-old male without previous asbestos exposure with peritoneal MM that initially responded to chemotherapy with cisplatin and gemcitabine but ultimately metastasized to his chest. He was diagnosed with MM based on histology, extensive immunohistochemical analyses, and an elevated serum CA-125 level. Cytogenetics and comparative genomic hybridization (CGH) analysis of his tumor identified a single extra copy number of chromosome 11 with few other changes noted.}, } @article {pmid22960065, year = {2013}, author = {Finkelstein, MM}, title = {Letter concerning the paper by Finley and colleagues: dx.doi.org/10.1016/j.yrtph.2012.05.015.}, journal = {Regulatory toxicology and pharmacology : RTP}, volume = {65}, number = {1}, pages = {178-179}, doi = {10.1016/j.yrtph.2012.08.016}, pmid = {22960065}, issn = {1096-0295}, mesh = {Asbestos, Serpentine/*adverse effects ; Female ; Humans ; Male ; Mesothelioma/*epidemiology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*epidemiology ; *Work ; }, } @article {pmid22953234, year = {2012}, author = {Macfarlane, E and Benke, G and Sim, MR and Fritschi, L}, title = {OccIDEAS: An Innovative Tool to Assess Past Asbestos Exposure in the Australian Mesothelioma Registry.}, journal = {Safety and health at work}, volume = {3}, number = {1}, pages = {71-76}, pmid = {22953234}, issn = {2093-7997}, abstract = {Malignant mesothelioma is an uncommon but rapidly fatal disease for which the principal aetiological agent is exposure to asbestos. Mesothelioma is of particular significance in Australia where asbestos use was very widespread from the 1950s until the 1980s. Exposure to asbestos includes occupational exposure associated with working with asbestos or in workplaces where asbestos is used and also 'take-home' exposure of family members of asbestos exposed workers. Asbestos exposure may also be non-occupational, occurring as a consequence of using asbestos products in non-occupational contexts and passive exposure is also possible, such as exposure to asbestos products in the built environment or proximity to an environmental source of exposure, for example an asbestos production plant. The extremely long latency period for this disease makes exposure assessment problematic in the context of a mesothelioma registry. OccIDEAS, a recently developed online tool for retrospective exposure assessment, has been adapted for use in the Australian Mesothelioma Registry (AMR) to enable systematic retrospective exposure assessment of consenting cases. Twelve occupational questionnaire modules and one non-occupational module have been developed for the AMR, which form the basis of structured interviews using OccIDEAS, which also stores collected data and provides a framework for generating metrics of exposure.}, } @article {pmid22953226, year = {2012}, author = {Park, EK and Yates, DH and Creaney, J and Thomas, PS and Robinson, BW and Johnson, AR}, title = {Association of biomarker levels with severity of asbestos-related diseases.}, journal = {Safety and health at work}, volume = {3}, number = {1}, pages = {17-21}, pmid = {22953226}, issn = {2093-7997}, abstract = {OBJECTIVES: Asbestos-related diseases (ARDs) have increased globally over the decades, causing an economic burden and increased health care costs. It is difficult to predict the risk of development of ARDs and of respiratory disability among workers with a history of asbestos exposure. Blood based biomarkers have been reported as promising tools for the early detection of malignant mesothelioma. This study investigated whether serum soluble mesothelin-related peptide (SMRP) would reflect severity of disablement in compensable ARDs.

METHODS: SMRP levels were measured in a cohort of 514 asbestos-exposed subjects. Severity of ARDs was assessed by a Medical Authority comprising four specially qualified respiratory physicians. Severity of ARDs and SMRP levels were compared.

RESULTS: Mean (standard deviation) serum SMRP level in the population with compensable ARDs (n = 150) was 0.95 (0.65) nmol/L, and was positively associated with disability assessment (p = 0.01). Mean SMRP level in healthy asbestos-exposed subjects was significantly lower than those with pleural plaques (p < 0.0001) and in subjects with ARDs who received compensation (p < 0.01).

CONCLUSION: This study indicates that serum SMRP levels correlate with severity of compensable ARDs. Serum SMRP could potentially be applied to monitor progress of ARDs. Further prospective work is needed to confirm the relationship between SMRP and disability assessment in this population.}, } @article {pmid22953203, year = {2011}, author = {Lim, JW and Koh, D and Khim, JS and Le, GV and Takahashi, K}, title = {Preventive measures to eliminate asbestos-related diseases in singapore.}, journal = {Safety and health at work}, volume = {2}, number = {3}, pages = {201-209}, pmid = {22953203}, issn = {2093-7997}, abstract = {The incidence of asbestos-related diseases (ARD) has increased in the last four decades. In view of the historical use of asbestos in Singapore since the country started banning it in phases in 1989 and the long latency of the disease, the incidence of ARD can be expected to increase further. As occupational exposure to asbestos still occurs, preventive measures to eliminate ARD continue to be required to protect the health of both workers and the public from asbestos exposure. The majority of occupational exposures to asbestos at present occur during the removal of old buildings. Preventive measures have been utilized by different government ministries and agencies in eliminating ARD in Singapore over the past 40 years. These measures have included the enforcement of legislation, substitution with safer materials, and engineering controls during asbestos removal as well as improvements in personal hygiene and the use of personal protective equipment. The existing Workman's Compensation System for ARD should be further refined, given that is currently stipulates that claims for asbestosis and malignant mesothelioma be made within 36 and 12 months after ceasing employment.}, } @article {pmid22949586, year = {2012}, author = {Sorahan, T}, title = {Cancer incidence in UK electricity generation and transmission workers, 1973-2008.}, journal = {Occupational medicine (Oxford, England)}, volume = {62}, number = {7}, pages = {496-505}, doi = {10.1093/occmed/kqs152}, pmid = {22949586}, issn = {1471-8405}, mesh = {Electricity/*adverse effects ; Female ; Humans ; Incidence ; Male ; Melanoma/*epidemiology ; Mesothelioma/*epidemiology ; Neoplasms/*epidemiology/etiology ; Occupational Diseases/*epidemiology/etiology ; Occupational Exposure/prevention & control/*statistics & numerical data ; *Power Plants ; Registries ; Surveys and Questionnaires ; United Kingdom/epidemiology ; }, abstract = {BACKGROUND: The effects of magnetic field exposure on cancer risks remains unclear.

AIMS: To examine cancer incidence among a cohort of UK electricity generation and transmission workers.

METHODS: Cancer morbidity experienced by a cohort of 81 842 employees of the former Central Electricity Generating Board of England and Wales was investigated for the period 1973-2008. All employees had worked for at least 6 months with some employment between 1973 and 1982. Standardized registration ratios (SRRs) were calculated on the basis of national rates.

RESULTS: Overall cancer morbidity was slightly below expectation in males and females. Significant excesses were found in male workers for mesothelioma (Observed [Obs] 504, SRR 331), skin cancer (non-melanoma) (Obs 3187, SRR 107) and prostate cancer (Obs 2684, SRR 107) and in female workers for cancer of the small intestine (Obs 10, SRR 306) and nasal cancer (Obs 9, SRR 474). Brain cancers were close to expectation in males and below expectation in females. Leukaemia incidence (all types) was slightly below expectation in males and females. More detailed analyses showed import ant contrasts for mesothelioma and leukaemia.

CONCLUSIONS: The clear occupational excess of mesothelioma was not matched by a corresponding excess of lung cancer, and the level of asbestos-induced lung cancer in this industry must be low. Leukaemia risks declined with period from hire; confident interpretation of this finding is not possible. The excesses of cancers of the nasal cavities and small intestine are probably not occupational, though the excess of skin cancer may be due to outdoor work.}, } @article {pmid22938569, year = {2012}, author = {Xu, J and Futakuchi, M and Shimizu, H and Alexander, DB and Yanagihara, K and Fukamachi, K and Suzui, M and Kanno, J and Hirose, A and Ogata, A and Sakamoto, Y and Nakae, D and Omori, T and Tsuda, H}, title = {Multi-walled carbon nanotubes translocate into the pleural cavity and induce visceral mesothelial proliferation in rats.}, journal = {Cancer science}, volume = {103}, number = {12}, pages = {2045-2050}, pmid = {22938569}, issn = {1349-7006}, mesh = {Animals ; Asbestos, Crocidolite/adverse effects ; *Cell Proliferation ; Lung/drug effects/pathology ; Macrophages, Alveolar/pathology ; Male ; Mesothelioma/*etiology/metabolism/pathology ; Nanotubes, Carbon/*adverse effects/chemistry ; Pleural Cavity/*pathology ; Rats ; Rats, Inbred F344 ; }, abstract = {Multi-walled carbon nanotubes have a fibrous structure similar to asbestos and induce mesothelioma when injected into the peritoneal cavity. In the present study, we investigated whether carbon nanotubes administered into the lung through the trachea induce mesothelial lesions. Male F344 rats were treated with 0.5 mL of 500 μg/mL suspensions of multi-walled carbon nanotubes or crocidolite five times over a 9-day period by intrapulmonary spraying. Pleural cavity lavage fluid, lung and chest wall were then collected. Multi-walled carbon nanotubes and crocidolite were found mainly in alveolar macrophages and mediastinal lymph nodes. Importantly, the fibers were also found in the cell pellets of the pleural cavity lavage, mostly in macrophages. Both multi-walled carbon nanotube and crocidolite treatment induced hyperplastic proliferative lesions of the visceral mesothelium, with their proliferating cell nuclear antigen indices approximately 10-fold that of the vehicle control. The hyperplastic lesions were associated with inflammatory cell infiltration and inflammation-induced fibrotic lesions of the pleural tissues. The fibers were not found in the mesothelial proliferative lesions themselves. In the pleural cavity, abundant inflammatory cell infiltration, mainly composed of macrophages, was observed. Conditioned cell culture media of macrophages treated with multi-walled carbon nanotubes and crocidolite and the supernatants of pleural cavity lavage fluid from the dosed rats increased mesothelial cell proliferation in vitro, suggesting that mesothelial proliferative lesions were induced by inflammatory events in the lung and pleural cavity and likely mediated by macrophages. In conclusion, intrapulmonary administration of multi-walled carbon nanotubes, like asbestos, induced mesothelial proliferation potentially associated with mesothelioma development.}, } @article {pmid22937893, year = {2012}, author = {Verma, DK and Clark, NE}, title = {Asbestos fiber burden in lung tissues of occupationally exposed workers.}, journal = {Journal of occupational and environmental hygiene}, volume = {9}, number = {10}, pages = {D177-82}, doi = {10.1080/15459624.2012.711606}, pmid = {22937893}, issn = {1545-9632}, mesh = {Air Pollutants, Occupational/*analysis ; Asbestos/*analysis ; Humans ; Lung/*chemistry ; Lung Neoplasms/chemically induced ; Male ; Mesothelioma/chemically induced ; Mineral Fibers/analysis ; Occupational Exposure/adverse effects/*analysis ; Ontario ; }, } @article {pmid22918238, year = {2012}, author = {Fujii, M and Nakanishi, H and Toyoda, T and Tanaka, I and Kondo, Y and Osada, H and Sekido, Y}, title = {Convergent signaling in the regulation of connective tissue growth factor in malignant mesothelioma: TGFβ signaling and defects in the Hippo signaling cascade.}, journal = {Cell cycle (Georgetown, Tex.)}, volume = {11}, number = {18}, pages = {3373-3379}, pmid = {22918238}, issn = {1551-4005}, mesh = {Animals ; Connective Tissue Growth Factor/genetics/*metabolism ; Epithelium/metabolism/pathology ; Female ; Humans ; Mesothelioma/genetics/*metabolism/pathology/therapy ; Mice ; Mice, Nude ; Molecular Targeted Therapy ; Mutation/genetics ; Promoter Regions, Genetic/genetics ; Protein Serine-Threonine Kinases/*metabolism ; *Signal Transduction ; Transforming Growth Factor beta/*metabolism ; }, abstract = {Malignant mesothelioma (MM) is a neoplasm that arises from serosal surfaces of the pleural, peritoneal and pericardial cavities with worldwide incidence, much of which is caused by asbestos exposure. Patients suffer from pain and dyspnea due to direct invasion of the chest wall, lungs and vertebral or intercostal nerves by masses of thick fibrotic tumors. Although there has been recent progress in the clinical treatment, current therapeutic approaches do not provide satisfactory results. Therefore, development of a molecularly targeted therapy for MM is urgently required. Our recent studies suggest that normal mesothelial and MM cell growth is promoted by TGFβ, and that TGFβ signaling together with intrinsic disturbances in neurofibromatosis type 2 (NF2) and Hippo signaling cascades in MM cells converges upon further expression of connective tissue growth factor (CTGF). The formation of a YAP-TEAD4-Smad3-p300 complex on the specific CTGF promoter site with an adjacent TEAD and Smad binding motif is a critical and synergistic event caused by the dysregulation of these two distinct cascades. Furthermore, we demonstrated the functional importance of CTGF through the mouse studies and human histological analyses, which may elucidate the clinical features of MM with severe fibrosis in the thoracic cavity.}, } @article {pmid22911649, year = {2013}, author = {Chamming's, S and Clin, B and Brochard, P and Astoul, P and Ducamp, S and Galateau-Salle, F and Ilg, AG and Goldberg, M and Gramond, C and Imbernon, E and Rolland, P and Pairon, JC}, title = {Compensation of pleural mesothelioma in France: data from the French National Mesothelioma Surveillance Programme.}, journal = {American journal of industrial medicine}, volume = {56}, number = {2}, pages = {146-154}, doi = {10.1002/ajim.22106}, pmid = {22911649}, issn = {1097-0274}, mesh = {Adult ; Aged ; Aged, 80 and over ; Air Pollutants/toxicity ; Asbestos/toxicity ; *Compensation and Redress ; Environmental Exposure/adverse effects/economics ; Female ; France ; Humans ; Male ; Mesothelioma/*economics/etiology ; Middle Aged ; National Health Programs/economics/statistics & numerical data ; Occupational Diseases/*economics/etiology ; Pleural Neoplasms/*economics/etiology ; Population Surveillance ; Workers' Compensation/*statistics & numerical data ; }, abstract = {BACKGROUND: The aim of this study was to determine the rates of compensation awarded to patients presenting with pleural mesothelioma and factors linked to such compensation in France.

METHODS: The study population consisted of 2,407 patients presenting with pleural mesothelioma, recorded by the National Mesothelioma Surveillance Programme between January 1, 1999 and December 31, 2009. Analysis of claims for recognition as "occupational disease" (OD) and claims for compensation by the Compensation Fund for Asbestos Victims (FIVA) were analyzed.

RESULTS: Approximately 30% of subjects presenting with pleural mesothelioma, affiliated to the General National Health Insurance fund, neither sought recognition as an OD nor claimed for FIVA compensation. Gender, age at diagnosis, type of health insurance, and socio-professional category influence the likelihood of patients presenting with mesothelioma seeking compensation for this disease.

CONCLUSIONS: Results show an under-compensation of pleural mesothelioma as OD and by the FIVA in France.}, } @article {pmid22909129, year = {2013}, author = {Kao, SC and Clarke, S and Vardy, J and Corte, P and Clarke, C and van Zandwijk, N}, title = {Patterns of care for malignant pleural mesothelioma patients compensated by the Dust Diseases Board in New South Wales, Australia.}, journal = {Internal medicine journal}, volume = {43}, number = {4}, pages = {402-410}, doi = {10.1111/j.1445-5994.2012.02925.x}, pmid = {22909129}, issn = {1445-5994}, mesh = {Aged ; Aged, 80 and over ; *Dust/prevention & control ; Female ; Humans ; Male ; Mesothelioma/diagnosis/epidemiology/*therapy ; Middle Aged ; New South Wales/epidemiology ; *Occupational Exposure/prevention & control ; Patient Care/methods/trends ; Pleural Neoplasms/diagnosis/epidemiology/*therapy ; Practice Patterns, Physicians'/*trends ; Treatment Outcome ; Workers' Compensation/*trends ; }, abstract = {BACKGROUND: The silent epidemic of mesothelioma in Australia is steadily increasing, and 30% of cases occur in New South Wales (NSW).

AIM: To describe the patterns of care and outcomes of patients with malignant pleural mesothelioma (MPM) in NSW.

METHODS: MPM patients in NSW applying for compensation at the NSW Dust Diseases Board from 2007 to 2009 were included. Survival from time of diagnosis was determined by the Kaplan-Meier method. The Chi-squared test was used to determine if there was an association between utilisation of treatment and geographical location.

RESULTS: A total of 138 patients was included: median age was 72.5; 91.3% male; 60.1% epithelial subtype; and 65.2% lived in major cities. All patients had at least one chest X-ray and computed tomography scan, and 21% had a positron emission tomography scan; 93.5% and 4.3% had histological or cytological confirmation respectively. Thoracoscopy (59.4%) was the most commonly used diagnostic procedure. Treatment utilisation: 53.6% chemotherapy; 35.5% radiotherapy; 9.4% extrapleural pneumonectomy (EPP); and 72.5% had palliative care involvement. There were no major differences in treatment utilisation between patients living in major cities and those in regional NSW (chemotherapy P = 0.42; radiotherapy P = 0.13 and palliative care P = 0.60), except for a higher rate of EPP in regional patients (16.7% vs 5.6%; P = 0.03). Median survival was 9.7 versus 12.3 months for city and regional patients respectively (P = 0.22).

CONCLUSION: Survival and treatment utilisation was not significantly different between MPM patients living in major cities and regional NSW, except for a higher rate of EPP in patients in regional NSW.}, } @article {pmid22886909, year = {2013}, author = {Reid, A and Franklin, P and Olsen, N and Sleith, J and Samuel, L and Aboagye-Sarfo, P and de Klerk, N and Musk, AW}, title = {All-cause mortality and cancer incidence among adults exposed to blue asbestos during childhood.}, journal = {American journal of industrial medicine}, volume = {56}, number = {2}, pages = {133-145}, doi = {10.1002/ajim.22103}, pmid = {22886909}, issn = {1097-0274}, mesh = {Adolescent ; Adult ; Aged ; Air Pollutants/analysis/*toxicity ; Asbestos, Crocidolite/analysis/*toxicity ; Child ; Child, Preschool ; Environmental Exposure/*adverse effects/analysis ; Environmental Monitoring ; Female ; Follow-Up Studies ; Humans ; Incidence ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Mining ; *Mortality ; Neoplasms/epidemiology/*etiology ; Registries ; Western Australia/epidemiology ; Young Adult ; }, abstract = {BACKGROUND: There are few data on the long-term health outcomes of exposure to asbestos in childhood. This study investigated cancer and mortality of adults exposed to blue asbestos as children.

METHODS: Data linkage to relevant health registries was used to identify cancers and mortality in a cohort of adults (n = 2,460) that had lived in an asbestos mining town during their childhood (<15 years).

RESULTS: There were 217 (93 female) incident cancers and 218 (70 female) deaths among the cohort. Compared with the Western Australian population females had elevated mesothelioma, ovarian and brain cancers, and increased "all cause" and "all cancer" mortality. Males had elevated mesothelioma, leukemia, prostate, brain, and colorectal cancers, and excess mortality from "all causes," "all cancers," circulatory disease, diseases of the nervous system, and accidents.

CONCLUSION: Exposure to blue asbestos in childhood is associated with an increased risk of cancer and mortality in adults.}, } @article {pmid22875734, year = {2012}, author = {Baur, X and Schneider, J and Woitowitz, HJ and Velasco Garrido, M}, title = {[Do advers health effects of chrysotile and amphibole asbestos differ?].}, journal = {Pneumologie (Stuttgart, Germany)}, volume = {66}, number = {8}, pages = {497-506}, doi = {10.1055/s-0032-1309980}, pmid = {22875734}, issn = {1438-8790}, mesh = {Asbestos, Amphibole/*poisoning ; Asbestos, Serpentine/*poisoning ; Asbestosis/*etiology/*mortality ; Evidence-Based Medicine ; Humans ; Knowledge Discovery ; Lung Neoplasms/*chemically induced/*mortality ; Prevalence ; Risk Factors ; Survival Analysis ; Survival Rate ; }, abstract = {Due to the current query whether the predominantly used chrysotile (white) asbestos comprises health risks we performed a literature search including in vitro and animal experiments as well as epidemiological studies.As shown by epidemiological studies chrysotile causes less pleural fibrosis and mesotheliomas when compared with other asbestos types. However, its otherwise inflammatory, toxic, carcinogenic, and fibrosis-inducing effects correspond to those of other occupationally relevant asbestos types. This is based on clinical, animal as well as on in-vitro findings. This means that denying a causal relationship, e. g. in a case with lung fibrosis (= asbestosis) or lung cancer with an asbestos load of 25 fiber-years in the absence of identification of a significant concentration of asbestos fibers or asbestos bodies in the lung (see so-called "hit and run" phenomenon), contradicts the medical-scientific knowledge.}, } @article {pmid22870590, year = {2012}, author = {Rodríguez Portal, JA}, title = {Asbestos-related disease: screening and diagnosis.}, journal = {Advances in clinical chemistry}, volume = {57}, number = {}, pages = {163-185}, pmid = {22870590}, issn = {0065-2423}, mesh = {Animals ; Asbestosis/*diagnosis/diagnostic imaging ; Biomarkers ; Biomarkers, Tumor/analysis ; GPI-Linked Proteins/analysis/genetics ; Humans ; Mass Screening ; Mesothelin ; Mesothelioma/diagnosis/diagnostic imaging/etiology ; Pleural Neoplasms/diagnosis/diagnostic imaging/etiology ; Prognosis ; Radiography, Thoracic ; }, abstract = {Malignant pleural mesothelioma (MPM) is an extremely aggressive tumor which develops in the epithelial lining of the lungs. Exposure to asbestos is the most influential risk factor for developing this disease. Despite recent advances in the treatment of other types of cancer, patients with mesothelioma currently face a poor prognosis. Therefore, it is highly important to develop an early diagnostic method with the greatest challenge on screening techniques to detect the disease at a subclinical stage. Early detection is critical for the development of more effective therapies in these patients. Unfortunately, radiologic studies have not proven effective. Biomarkers might be a useful adjunct tool among populations previously exposed to asbestos. This review will provide an update of recent progress in serum biomarkers (osteopontin (OPN), soluble mesothelin (SM), and megakaryocyte potentiating factor (MPF)) to diagnose, detect, and monitor MPM. Of these, SM has demonstrated the greatest diagnostic potential although MPF may serve as an equal alternative. Despite recent studies, it is apparent that long-term large-cohort research is required to conclusively demonstrate the usefulness of these markers in this disease.}, } @article {pmid22864872, year = {2012}, author = {Jiang, L and Akatsuka, S and Nagai, H and Chew, SH and Ohara, H and Okazaki, Y and Yamashita, Y and Yoshikawa, Y and Yasui, H and Ikuta, K and Sasaki, K and Kohgo, Y and Hirano, S and Shinohara, Y and Kohyama, N and Takahashi, T and Toyokuni, S}, title = {Iron overload signature in chrysotile-induced malignant mesothelioma.}, journal = {The Journal of pathology}, volume = {228}, number = {3}, pages = {366-377}, doi = {10.1002/path.4075}, pmid = {22864872}, issn = {1096-9896}, mesh = {Animals ; Asbestos, Serpentine/*adverse effects/pharmacology ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Biomarkers, Tumor/*metabolism ; Cell Transformation, Neoplastic/drug effects ; DNA Copy Number Variations/drug effects ; DNA, Neoplasm/drug effects ; Disease Models, Animal ; Homeodomain Proteins/metabolism ; Iron/metabolism ; Iron Overload/*metabolism ; Lung Neoplasms/*chemically induced/*metabolism/pathology ; Male ; Mesothelioma/*chemically induced/*metabolism/pathology ; Mesothelioma, Malignant ; Nitrilotriacetic Acid/pharmacology ; Peritoneal Neoplasms/*chemically induced/*metabolism/pathology ; Rats ; Rats, Inbred BN ; Rats, Inbred F344 ; Signal Transduction/drug effects ; Transcription Factors/metabolism ; }, abstract = {Exposure to asbestos is a risk for malignant mesothelioma (MM) in humans. Among the commercially used types of asbestos (chrysotile, crocidolite, and amosite), the carcinogenicity of chrysotile is not fully appreciated. Here, we show that all three asbestos types similarly induced MM in the rat peritoneal cavity and that chrysotile caused the earliest mesothelioma development with a high fraction of sarcomatoid histology. The pathogenesis of chrysotile-induced mesothelial carcinogenesis was closely associated with iron overload: repeated administration of an iron chelator, nitrilotriacetic acid, which promotes the Fenton reaction, significantly reduced the period required for carcinogenesis; massive iron deposition was found in the peritoneal organs with high serum ferritin; and homozygous deletion of the CDKN2A/2B/ARF tumour suppressor genes, the most frequent genomic alteration in human MM and in iron-induced rodent carcinogenesis, was observed in 92.6% of the cases studied with array-based comparative genomic hybridization. The induced rat MM cells revealed high expression of mesoderm-specific transcription factors, Dlx5 and Hand1, and showed an iron regulatory profile of active iron uptake and utilization. These data indicate that chrysotile is a strong carcinogen when exposed to mesothelia, acting through the induction of local iron overload. Therefore, an intervention to remove local excess iron might be a strategy to prevent MM after asbestos exposure.}, } @article {pmid22858896, year = {2013}, author = {de Klerk, N and Alfonso, H and Olsen, N and Reid, A and Sleith, J and Palmer, L and Berry, G and Musk, AB}, title = {Familial aggregation of malignant mesothelioma in former workers and residents of Wittenoom, Western Australia.}, journal = {International journal of cancer}, volume = {132}, number = {6}, pages = {1423-1428}, doi = {10.1002/ijc.27758}, pmid = {22858896}, issn = {1097-0215}, mesh = {Adult ; Aged ; Asbestos, Crocidolite/*adverse effects ; Family ; Female ; Humans ; Male ; Mesothelioma/*etiology/*genetics ; Middle Aged ; Occupational Exposure/*adverse effects ; Risk ; Western Australia ; }, abstract = {Clustering of cases of malignant mesothelioma within families has often been observed, but disentangling genetic and exposure effects has not been done. Former workers and residents exposed to crocidolite at Wittenoom, Western Australia, where many families shared exposure to asbestos, have had high rates of mesothelioma. Our study aimed to estimate the additional risk of mesothelioma in relatives, after allowance for common exposure to crocidolite. More than 11,000 former asbestos workers and residents from Wittenoom have been followed up in cancer and death registries. Levels of exposure for all members of the Wittenoom cohorts have been estimated previously. Relationships between family members of all mesothelioma cases were established from questionnaires, birth and death certificates. Expected numbers of cases of mesothelioma were estimated by fitting a Weibull survival model to all data, based on time from first asbestos exposure, duration and intensity of exposure and age. For each family group, the earliest case was considered the index case. Predicted risk was estimated for each subject from the time of diagnosis of the index case. Familial risk ratios were estimated by dividing observed cases by the sum of risks of all same degree relatives of index cases. There were 369 family groups with at least one case of mesothelioma and a further 25 cases of mesothelioma among relatives in the same families, with 12.9 expected. The risk ratio for blood relatives was 1.9 (95% confidence interval [CI] = 1.3-2.9, p = 0.002). These findings suggest an important, but not large, genetic component in mesothelioma, similar to many other cancers.}, } @article {pmid22849735, year = {2012}, author = {Oviedo, SP and Cagle, PT}, title = {Diffuse malignant mesothelioma.}, journal = {Archives of pathology & laboratory medicine}, volume = {136}, number = {8}, pages = {882-888}, doi = {10.5858/arpa.2012-0142-CR}, pmid = {22849735}, issn = {1543-2165}, mesh = {Aged ; Diagnosis, Differential ; Humans ; Lung/*pathology ; Lung Neoplasms/*diagnosis/pathology/physiopathology ; Male ; Mesothelioma/*diagnosis/pathology/physiopathology/secondary ; Muscle Neoplasms/secondary ; Muscle, Skeletal/pathology ; Pleural Effusion, Malignant/etiology ; Pleurisy/diagnosis ; }, abstract = {Diffuse malignant mesothelioma (DMM) is an uncommon cancer with great clinical significance because it currently remains an incurable disease, and most patients die within months after diagnosis. Although DMM incidence is leveling off or decreasing in developed countries because of the strict control of asbestos use, it is increasing in countries without adequate asbestos control. In some settings, benign, reactive mesothelial hyperplasias and organizing pleuritis can be difficult to differentiate from DMM and vice versa, and the variety of DMM's histopathologic features generates an extensive list of differential diagnoses with other malignancies, particularly, metastatic malignancies, which are more frequent in the pleura than are primary malignancies. These two issues are the topic of discussion in this review, along with a brief presentation of a case of DMM that presented in a 66-year-old man with recurrent, right pleural effusions, and in whom, diagnosis of DMM had not been suspected clinically, radiographically, surgically, grossly, or initially, on frozen section. It was not until focal invasion into the skeletal muscle was discovered on permanent sections that a diagnosis of DMM could be established.}, } @article {pmid22836805, year = {2012}, author = {Hama, R and Watanabe, Y and Shinada, K and Yamada, Y and Ogata, Y and Yoshida, Y and Tamura, T and Hiraishi, T and Oikawa, R and Sakurai, J and Maehata, T and Koizumi, H and Itoh, F}, title = {Characterization of DNA hypermethylation in two cases of peritoneal mesothelioma.}, journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine}, volume = {33}, number = {6}, pages = {2031-2040}, pmid = {22836805}, issn = {1423-0380}, mesh = {Adult ; Aged ; Base Sequence ; Biomarkers, Tumor/*genetics/metabolism ; *DNA Methylation ; DNA, Neoplasm/*genetics ; Female ; Humans ; Immunoenzyme Techniques ; Male ; Membrane Proteins/genetics ; Mesothelioma/*genetics/pathology/surgery ; Mitogen-Activated Protein Kinase 13/genetics ; Molecular Sequence Data ; Mutation/genetics ; Peritoneal Neoplasms/*genetics/pathology/surgery ; Pleural Neoplasms/*genetics/pathology/surgery ; Polymerase Chain Reaction ; Prognosis ; Proto-Oncogene Proteins/genetics ; Proto-Oncogene Proteins B-raf/genetics ; Proto-Oncogene Proteins p21(ras) ; Sarcoma/*genetics/pathology/surgery ; Serine Proteinase Inhibitors/genetics ; Tumor Suppressor Protein p53/genetics ; ras Proteins/genetics ; }, abstract = {Malignant mesothelioma (MM) is a rare disease with a poor prognosis. Pleural mesothelioma, which is the most common type of MM, is considered to be caused by asbestos exposure and is increasing in incidence, with about 15,000 new cases diagnosed worldwide annually. On the other hand, peritoneal mesothelioma is a very rare type of MM; thus, its pathogenesis is even less understood than pleural mesothelioma. Recent research on the pathogenesis of malignant pleural mesothelioma has indicated that both epigenetic and genetic alterations contribute to tumorigenesis. Here, we hypothesize that peritoneal mesothelioma also has an epigenetic alteration in the same genes (Kazal-type serine peptidase inhibitor domain 1 (KAZALD1), transmembrane protein 30B (TMEM30B), and mitogen-activated protein kinase 13 (MAPK13)). Our goal is to identify DNA methylation of these three candidate genes in two peritoneal mesothelioma cases. Laser capture microdissection was used to separate diseased sections of formalin-fixed paraffin-embedded samples from one surgically resected tissue (epithelial type) and one autopsy tissue (sarcomatous type). Genomic DNA was subsequently extracted by the standard phenol chloroform method. The DNA was then treated with sodium bisulphite, and pyrosequencing analysis was used to quantitatively analyze the methylation of candidate genes reported to be hypermethylated in malignant pleural mesothelioma (KAZALD1, TMEM30B, and MAPK13). TMEM30B and MAPK13 were not methylated in either case. However, KAZALD1 was highly methylated in sarcomatoid-type peritoneal mesothelioma. We first report that the KAZALD1 gene was hypermethylated in sarcomatoid-type malignant peritoneal mesothelioma.}, } @article {pmid22835614, year = {2013}, author = {Pantazopoulos, I and Boura, P and Xanthos, T and Syrigos, K}, title = {Effectiveness of mesothelin family proteins and osteopontin for malignant mesothelioma.}, journal = {The European respiratory journal}, volume = {41}, number = {3}, pages = {706-715}, doi = {10.1183/09031936.00226111}, pmid = {22835614}, issn = {1399-3003}, mesh = {Asbestos/adverse effects ; Biomarkers, Tumor/*metabolism ; Early Detection of Cancer ; GPI-Linked Proteins/*metabolism/urine ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/diagnosis/metabolism ; Mesothelin ; Mesothelioma/*diagnosis/metabolism ; Osteopontin/*metabolism ; Pleura/metabolism ; Pleural Neoplasms/diagnosis/*metabolism ; Prognosis ; Risk Assessment ; }, abstract = {Malignant mesothelioma (MM) is an aggressive tumour with poor prognosis whose early diagnosis is difficult. Mesothelin, megakaryocyte potentiating factor (MPF) and osteopontin have attracted attention as biomarkers. The aim of the present review is to provide an overview regarding these candidate biomarkers for MM, and discuss their potential role in today's clinical practice. Mesothelin and MPF have good specificity but sub-optimal sensitivity for detection of MM, being negative both in the sarcomatoid histological sub-type and in almost half of epithelioid mesothelioma, especially in the early stages. Osteopontin is a marker of the duration of asbestos exposure, but lacks specificity for mesothelioma. Several patient characteristics influence the diagnostic accuracy of biomarkers and make the establishment of the "optimal" diagnostic threshold difficult. Mesothelin and MPF have proved useful in assessing response to treatment. Combining different markers together may lead to an improvement in diagnostic accuracy, but there is still need for research in this area. Extensive validation and further research is required to improve the use of serum markers in mesothelioma management. In the near future, their application in clinical practice is probably in monitoring response to therapy, rather than in guiding diagnostic decisions and risk assessment of asbestos-exposed populations.}, } @article {pmid22829461, year = {2012}, author = {Furlan, C and Mortarino, C}, title = {Pleural mesothelioma: forecasts of the death toll in the area of Casale Monferrato, Italy.}, journal = {Statistics in medicine}, volume = {31}, number = {29}, pages = {4114-4134}, doi = {10.1002/sim.5523}, pmid = {22829461}, issn = {1097-0258}, mesh = {Asbestos/*toxicity ; *Environmental Exposure ; Female ; *Forecasting ; Humans ; Italy/epidemiology ; Male ; Mesothelioma/*mortality ; *Models, Statistical ; Pleural Neoplasms/*mortality ; }, abstract = {In the city of Casale Monferrato, the largest Italian factory that produced asbestos-cement goods was active from 1907 to 1985. Consequently, asbestos fibers scattered in the surrounding area and caused an enormous number of cases of pleural mesothelioma. Owing to the very long latency of this disease, many subjects have not exhibited its symptoms yet. The aim of this paper is to model and predict the future evolution of the number of deaths due to this disease among residents in the area around that city. The model used here is based on a cellular automata that is assumed to pass through three steps: exposure, contamination, and diagnosis. In this way, forecasts of the future evolution take into account the environmental conditions that changed over the last century because of different levels of plant activity. The model is fitted to annual diagnosis data from 1954 to 2008. Results show that deaths will not end until 2031 and that in the next two decades, at least 505 more subjects will be diagnosed with this disease.}, } @article {pmid22814683, year = {2013}, author = {Bayram, M and Dongel, I and Bakan, ND and Yalççn, H and Cevit, R and Dumortier, P and Nemery, B}, title = {High risk of malignant mesothelioma and pleural plaques in subjects born close to ophiolites.}, journal = {Chest}, volume = {143}, number = {1}, pages = {164-171}, doi = {10.1378/chest.11-2727}, pmid = {22814683}, issn = {1931-3543}, mesh = {Adult ; Aged ; Asbestos/*adverse effects/analysis ; *Carcinogens/analysis ; Case-Control Studies ; Environmental Exposure/*adverse effects/statistics & numerical data ; Female ; Geography/statistics & numerical data ; Housing ; Humans ; Lung Neoplasms/epidemiology/*etiology ; Male ; Mesothelioma/epidemiology/*etiology ; Mesothelioma, Malignant ; Middle Aged ; Pleural Diseases/epidemiology/etiology ; Pleural Neoplasms/epidemiology/*etiology ; *Residence Characteristics ; Risk Factors ; Soil/analysis ; Turkey/epidemiology ; X-Ray Diffraction ; }, abstract = {BACKGROUND: Ophiolites, a special sequence of geologic rock units, are known sources of naturally occurring asbestos. The aim of this study was to test whether the occurrence of malignant mesothelioma (MM) or pleural plaques (PPs) in the province of Sivas, Turkey, is determined by the proximity of the patient's birthplace to ophiolites and, if so, to establish the magnitude of the risk.

METHODS: The birthplaces of patients with MM or PPs (cases) and patients with prostate or breast cancer (control subjects), diagnosed between 2000 and 2010 and identified through a mandatory cancer registry or from hospital records (PPs), were located on a geologic map, and the nearest distance to ophiolites was measured. The relation of MM or PPs with distance to ophiolites was analyzed by logistic regression. Samples of soil and house plaster were determined by x-ray diffraction.

RESULTS: Patients with MM (n = 100) or PPs (n = 133) were born significantly nearer to ophiolites (median distance, 4.5 km for men, 0 km for women) than were patients with prostate cancer (n = 161) or breast cancer (n = 139) (median distance, 20 km for both). ORs were 1.6 (men) (P < .001) and 2.0 (women) (P < .001) for every 5-km decrease in the distance of birthplace to ophiolites for MM, compared with prostate and breast cancer, respectively.

CONCLUSION: In this area without substantial industrial asbestos use, there is an association between the occurrence of mesothelioma (and of PPs) and the proximity of the subject's birthplace to ophiolites.}, } @article {pmid22812632, year = {2013}, author = {Murphy, FA and Poland, CA and Duffin, R and Donaldson, K}, title = {Length-dependent pleural inflammation and parietal pleural responses after deposition of carbon nanotubes in the pulmonary airspaces of mice.}, journal = {Nanotoxicology}, volume = {7}, number = {6}, pages = {1157-1167}, doi = {10.3109/17435390.2012.713527}, pmid = {22812632}, issn = {1743-5404}, support = {G0901697/MRC_/Medical Research Council/United Kingdom ; /DH_/Department of Health/United Kingdom ; }, mesh = {Animals ; Inhalation Exposure/*adverse effects ; Mice ; Nanotubes, Carbon/*toxicity ; Pleura/*drug effects/pathology ; Pleurisy/*chemically induced ; }, abstract = {BACKGROUND: Carbon nanotubes (CNT) are fibre-like nanomaterials whose structural similarity to asbestos has raised concerns that they may also pose a mesothelioma hazard. The objective of this study was to examine the inflammatory potential of three CNT samples of differing length on the lungs and pleural cavity following introduction into the airspaces of mice.

RESULTS: Aspiration of the two short/tangled and one long CNT sample into the lungs of mice resulted in a length-dependent inflammatory response at 1 week, i.e., only the long CNT sample caused acute neutrophilic inflammation in bronchoalveolar lavage at 1 week and progressive thickening of the alveolar septa. The authors also report length-dependent inflammatory responses in the pleural lavage after exposure only to the long CNT. The inflammatory response in the pleural cavity to long fibres and the appearance of lesions along the chest wall and diaphragm was not present at 1 week and only evident by 6 weeks post-exposure.

CONCLUSION: Length-dependent pathogenicity is a feature of asbestos and the results presented in this study demonstrate similar length-dependent pathogenicity of CNT in the lungs and pleural space following airspace deposition. The data support the contention that long CNT reach the pleura from the airspaces, and that they are retained at the parietal pleura and cause inflammation and lesion development. The parietal pleura is the site of origin of mesothelioma and inflammation is considered to be a process involved in asbestos carcinogenesis and so the data support the contention that CNT may pose an asbestos-like mesothelioma hazard.}, } @article {pmid22784439, year = {2013}, author = {Kinoshita, Y and Takasu, K and Yuri, T and Yoshizawa, K and Uehara, N and Kimura, A and Miki, H and Tsubura, A and Shikata, N}, title = {Two cases of malignant peritoneal mesothelioma without asbestos exposure: cytologic and immunohistochemical features.}, journal = {Annals of diagnostic pathology}, volume = {17}, number = {1}, pages = {99-103}, doi = {10.1016/j.anndiagpath.2012.05.007}, pmid = {22784439}, issn = {1532-8198}, mesh = {Aged ; *Asbestos ; Calbindin 2 ; Humans ; Lung Neoplasms/etiology/*metabolism/*pathology ; Male ; Mesothelioma/etiology/*metabolism/*pathology ; Mesothelioma, Malignant ; Mucin-1/metabolism ; Peritoneal Neoplasms/etiology/*metabolism/*pathology ; Peritoneum/metabolism/pathology ; S100 Calcium Binding Protein G/metabolism ; Vimentin/metabolism ; }, abstract = {Approximately half a century has passed since asbestos was first reported to be the main cause of malignant mesothelioma; yet the incidence of this disease continues to increase worldwide. Twenty percent of cases occur without prior asbestos exposure, and in these patients, malignant peritoneal mesothelioma is more common than malignant pleural mesothelioma. Here, we report the cytomorphologic and immunohistochemical features of 2 cases of malignant peritoneal mesothelioma where there was no history of asbestos exposure. Ascitic cytology showed that most cells were isolated and that clusters were rarely observed, but the findings were consistent with malignant mesothelioma in both cases. Immunohistochemical analysis for epithelial membrane antigen, calretinin, vimentin, β-catenin, melan-A, glucose transporter-1, cytokeratin CAM5.2, Wilms tumor antigen-1, D2-40, CD146, progesterone receptor, estrogen receptor, and cytokeratin 5/6 was indicative of malignant mesothelioma. In malignant mesothelioma without prior asbestos exposure, the etiology and prognostic significance is still unclear. Further study is needed to clarify this point.}, } @article {pmid22781011, year = {2012}, author = {Otsuki, T and Hirano, S}, title = {[Regarding the special feature of "the frontline of nanoparticle research": progress of the Study Group on Fibrous and Particulate Substances (SGFPS)].}, journal = {Nihon eiseigaku zasshi. Japanese journal of hygiene}, volume = {67}, number = {3}, pages = {375-382}, doi = {10.1265/jjh.67.375}, pmid = {22781011}, issn = {0021-5082}, mesh = {Asbestos/*toxicity ; Humans ; Mesothelioma/chemically induced ; Nanoparticles/*toxicity ; }, abstract = {Among the symposia organized by various study groups in the Japanese Society of Hygiene (JSH), the Study Group on Fibrous and Particulate Substances (SGFPS) presented a symposium entitled "The frontline of nanoparticle research" chaired by Professor Takemi Otsuki (Kawasaki Medical School, Japan) and Dr. Seishiro Hirano (National Institute for Environmental Studies, Japan) on 26 March, 2012, as a part of the program of the 82nd Annual Meeting of JSH in Kyoto, Japan. Special features consist of three presentations given at the above-mentioned symposium. In this article, we introduce the progress of the Study Group on Fibrous and Particulate Substances (SGFPS) from the initial symposium entitled "Asbestos: Science and Society" held at the 76th Annual Meeting of JSH at Ube, Japan to the last above-mentioned symposium in Kyoto. The health-related issues caused by exposure to fibrous materials such as asbestos and also particulated substances such as nanoparticles will be lasting in the future and researchers including our study group have to make their best efforts to resolve these problems and to reduce health impairments due to exposure to environmental fibrous and particulated substances.}, } @article {pmid22762491, year = {2012}, author = {Reid, A and Alfonso, H and Ti, JS and Wong, E and de Klerk, N and Musk, AW}, title = {Sense of control and wellbeing decades after exposure to blue asbestos at Wittenoom, Western Australia.}, journal = {International journal of occupational and environmental health}, volume = {18}, number = {2}, pages = {116-123}, doi = {10.1179/1077352512Z.0000000006}, pmid = {22762491}, issn = {2049-3967}, mesh = {Asbestos ; *Asbestos, Crocidolite ; Humans ; *Mesothelioma/epidemiology ; Occupational Exposure ; Western Australia ; }, abstract = {OBJECTIVE: The objective of this study was to examine the impact of the knowledge of past asbestos exposure on psychosocial health.

METHODS: Blue asbestos was mined and milled at Wittenoom in Western Australia between 1943 and 1966. In 2007, SF-12 and Locus of Control (LOC) questionnaires were sent to 5,101 surviving Wittenoom workers and residents. Wellbeing scores and LOC scores were then examined in relation to quantitative exposure measures using linear regression.

RESULTS: Wellbeing scores were lower among Wittenoom workers and residents compared with the Western Australian population, although an exposure-response relationship with cumulative asbestos exposure was not found. Those who arrived in Wittenoom as children had a more external sense of control than those who arrived there as adults. There was a 0·12 increase in LOC with a 2·7-fold increase in cumulative asbestos exposure (f/ml-years) (P<0·01).

CONCLUSIONS: The study concluded that asbestos operation at Wittenoom may have had a detrimental impact on former workers' and residents' sense of control over their lives.}, } @article {pmid22762485, year = {2012}, author = {Bohme, SR}, title = {Expression of concern: false claim to be free of conflicts in asbestos biopersistence debate.}, journal = {International journal of occupational and environmental health}, volume = {18}, number = {2}, pages = {85-88}, doi = {10.1179/1077352512Z.00000000024}, pmid = {22762485}, issn = {2049-3967}, mesh = {Animals ; Asbestos, Serpentine/*chemistry/*pharmacokinetics ; Environmental Exposure/*adverse effects ; Humans ; Lung Neoplasms/*chemically induced/*etiology ; Mesothelioma/*chemically induced/*etiology ; }, } @article {pmid22761781, year = {2012}, author = {Newick, K and Cunniff, B and Preston, K and Held, P and Arbiser, J and Pass, H and Mossman, B and Shukla, A and Heintz, N}, title = {Peroxiredoxin 3 is a redox-dependent target of thiostrepton in malignant mesothelioma cells.}, journal = {PloS one}, volume = {7}, number = {6}, pages = {e39404}, pmid = {22761781}, issn = {1932-6203}, support = {T32 ES007122/ES/NIEHS NIH HHS/United States ; T32 ES007122-29/ES/NIEHS NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/*pharmacology ; Dose-Response Relationship, Drug ; Forkhead Box Protein M1 ; Forkhead Transcription Factors/metabolism ; Humans ; Lung Neoplasms/*metabolism ; Mesothelioma/*metabolism ; Mesothelioma, Malignant ; Mitochondria/drug effects/metabolism ; Oxidation-Reduction ; Peroxiredoxin III/*metabolism ; Signal Transduction/drug effects ; Superoxides/metabolism ; Thiostrepton/*pharmacology ; Tumor Cells, Cultured ; }, abstract = {Thiostrepton (TS) is a thiazole antibiotic that inhibits expression of FOXM1, an oncogenic transcription factor required for cell cycle progression and resistance to oncogene-induced oxidative stress. The mechanism of action of TS is unclear and strategies that enhance TS activity will improve its therapeutic potential. Analysis of human tumor specimens showed FOXM1 is broadly expressed in malignant mesothelioma (MM), an intractable tumor associated with asbestos exposure. The mechanism of action of TS was investigated in a cell culture model of human MM. As for other tumor cell types, TS inhibited expression of FOXM1 in MM cells in a dose-dependent manner. Suppression of FOXM1 expression and coincidental activation of ERK1/2 by TS were abrogated by pre-incubation of cells with the antioxidant N-acetyl-L-cysteine (NAC), indicating its mechanism of action in MM cells is redox-dependent. Examination of the mitochondrial thioredoxin reductase 2 (TR2)-thioredoxin 2 (TRX2)-peroxiredoxin 3 (PRX3) antioxidant network revealed that TS modifies the electrophoretic mobility of PRX3. Incubation of recombinant human PRX3 with TS in vitro also resulted in PRX3 with altered electrophoretic mobility. The cellular and recombinant species of modified PRX3 were resistant to dithiothreitol and SDS and suppressed by NAC, indicating that TS covalently adducts cysteine residues in PRX3. Reduction of endogenous mitochondrial TRX2 levels by the cationic triphenylmethane gentian violet (GV) promoted modification of PRX3 by TS and significantly enhanced its cytotoxic activity. Our results indicate TS covalently adducts PRX3, thereby disabling a major mitochondrial antioxidant network that counters chronic mitochondrial oxidative stress. Redox-active compounds like GV that modify the TR2/TRX2 network may significantly enhance the efficacy of TS, thereby providing a combinatorial approach for exploiting redox-dependent perturbations in mitochondrial function as a therapeutic approach in mesothelioma.}, } @article {pmid22760439, year = {2012}, author = {Wei, B and Jia, X and Ye, B and Yu, J and Zhang, B and Zhang, X and Lu, R and Dong, T and Yang, L}, title = {Impacts of land use on spatial distribution of mortality rates of cancers caused by naturally occurring asbestos.}, journal = {Journal of exposure science & environmental epidemiology}, volume = {22}, number = {5}, pages = {516-521}, doi = {10.1038/jes.2012.63}, pmid = {22760439}, issn = {1559-064X}, mesh = {Agriculture ; Asbestos/*toxicity ; China/epidemiology ; Female ; Geographic Information Systems ; Humans ; Intestinal Neoplasms/mortality ; Laryngeal Neoplasms/mortality ; Liver Neoplasms/mortality ; Lung Neoplasms/mortality ; Male ; Mesothelioma/mortality ; Nasopharyngeal Neoplasms/mortality ; Neoplasms/*mortality ; Sex Factors ; Stomach Neoplasms/mortality ; }, abstract = {This study investigated the spatial distributions of mortality rates of six cancers: mesothelioma, lung cancer, intestinal cancer, nasopharyngeal and laryngeal cancer, liver cancer, and stomach cancer in Dayao using Geographic Information Systems. Relationships between the mortality rates of the six cancers and land use patterns were investigated by Pearson Correlation Coefficients. The results indicated that the mortality rates of nasopharyngeal and laryngeal cancer, lung cancer, intestinal cancer, and mesothelioma were significantly associated with outcropped asbestos. Both the proportions of farmland and urban area were positively related to the mortality rates of nasopharyngeal and laryngeal cancer, lung cancer, intestinal cancer, and mesothelioma, and significant negative correlations were found between the proportion of forestland and nasopharyngeal and laryngeal cancer and intestinal cancer. It can be concluded that naturally occurring asbestos may significantly elevate the mortality rates of nasopharyngeal and laryngeal cancer, intestinal cancer, lung cancer, and mesothelioma. Moreover, higher proportions of farmland, urban area, and lower proportions of forested land may elevate the mortality rate of the four cancers.}, } @article {pmid22753293, year = {2012}, author = {Rothschild, S and Gautschi, O}, title = {[Chemotherapy for malignant tumors of lung and pleura].}, journal = {Therapeutische Umschau. Revue therapeutique}, volume = {69}, number = {7}, pages = {433-441}, doi = {10.1024/0040-5930/a000311}, pmid = {22753293}, issn = {0040-5930}, mesh = {Antineoplastic Agents/*therapeutic use ; Carcinoma, Non-Small-Cell Lung/*drug therapy ; Female ; Humans ; Lung Neoplasms/*drug therapy ; Male ; Pleural Neoplasms/*drug therapy ; }, abstract = {Lung Cancer is the leading cause of cancer-related mortality worldwide, with nearly 1.4 million deaths each year. There has been an overall decrease in the incidence of lung cancer in men, although in women this trend has only been noted very recently in the United States and in many countries in Western Europe. In contrast, in many parts of the world the number of cases and deaths related to lung cancer is on the rise. These increased death rates are in close correlation to smoking habits in the different countries. It is also increasingly becoming a disease of the elderly, with a median age at diagnosis of 70 years. In Switzerland about 2'500 men and 1'200 women are yearly diagnosed with lung cancer. Lung cancer is diagnosed at an advanced stage in a majority of patients, which explains the high mortality rate associated with this disease. In the current review we give on overview on the current treatment practice for small cell lung cancer (SCLC) as well as on non-small cell lung cancer (NSCLC). The main focus is on the novel treatment options for advanced, metastatic NSCLC and the current use of predictive biomarkers in order to personalize therapy. Malignant pleural mesothelioma is a rare cancer occurring mainly in older men who have been exposed to asbestos, although it occurs decades after exposure (20 - 40 years later). The disease is difficult to treat and median overall survival is only about one year.}, } @article {pmid24039630, year = {2012}, author = {Blackham, AU and Levine, EA}, title = {Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy for Malignant Peritoneal Mesothelioma.}, journal = {European journal of clinical & medical oncology}, volume = {4}, number = {2}, pages = {25-32}, pmid = {24039630}, issn = {1759-8958}, support = {P30 CA012197/CA/NCI NIH HHS/United States ; }, abstract = {Malignant peritoneal mesothelioma (MPM) is a rare and aggressive neoplasm that is largely resistant to traditional anti-cancer therapies. For years it has been considered a terminal condition and once diagnosed, patients generally survived less than a year despite aggressive treatment. Although rare, the worldwide incidence of MPM continues to rise, in part due to its association with asbestos exposure. Patients usually present with non-specific symptoms of abdominal distension and pain making the diagnosis challenging. In recent years, aggressive cytoreductive surgery with the administration of hyperthermic intraperitoneal chemotherapy (HIPEC) has improved survival in patients with MPM treated at multiple centers worldwide. This review article briefly highlights the presentation, diagnosis, and natural history of MPM. We then explore the available treatment options with primary focus on cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.}, } @article {pmid22740956, year = {2012}, author = {Murakami, A and Tabata, C and Tabata, R and Okuwa, H and Nakano, T}, title = {Clinical role of pleural effusion MMP-3 levels in malignant pleural mesothelioma.}, journal = {Oncology letters}, volume = {3}, number = {3}, pages = {581-585}, pmid = {22740956}, issn = {1792-1074}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive malignant tumor of mesothelial origin associated with asbestos exposure. MPM exhibits a limited response to conventional chemotherapy and radiotherapy. This, early diagnosis of MPM is essential. Malignant tumor progression requires the destruction of the basement membrane, which is constructed from extracellular matrix (ECM) materials. Various types of human tumor cells are reported to produce ECM-degrading proteases that are important in tumor progression. Among this group of proteolytic enzymes, matrix metalloproteinases (MMPs) are thought to be important due to their wide degrading function. We investigated the pleural effusion MMP-3 levels of patients with MPM and compared them with those of a population with non-malignant pleuritis or lung cancer involving malignant pleural effusion. The pleural effusion MMP-3 concentrations of 52 MPM patients and 67 non-MPM patients were measured. The results showed that the MPM patients had significantly higher pleural effusion MMP-3 levels than the population with non-malignant pleuritis. The overall survival of the MPM patients with lower pleural effusion MMP-3 levels was longer than that of patients with higher pleural effusion MMP-3 levels. Our data therefore suggest a clinical role of pleural effusion MMP-3 levels in malignant pleural mesothelioma.}, } @article {pmid22729565, year = {2013}, author = {Gatto, MP and Tanna, D}, title = {Distribution and trends in mesothelioma mortality in Italy from 1974 to 2006.}, journal = {International archives of occupational and environmental health}, volume = {86}, number = {4}, pages = {489-496}, pmid = {22729565}, issn = {1432-1246}, mesh = {Construction Industry/statistics & numerical data ; Death Certificates ; Female ; Humans ; Italy/epidemiology ; Male ; Mesothelioma/*mortality ; Mortality/trends ; Pleural Neoplasms/*mortality ; Ships/statistics & numerical data ; }, abstract = {PURPOSE: Using the epidemiological data of pleural cancer mortality, the authors estimated time trends and distribution of malignant mesothelioma in Italy during the period 1974-2006.

METHODS: To describe temporal trends of the standardized mortality ratios (SMRs) in all the 20 Italian regions, we applied the Joinpoint Regression Model, developed by the National Cancer Institute (USA). The 107 provincial SMRs are represented on maps by using the Arcview GIS software (version 3.2).

RESULTS: The high values from mesothelioma mortality in construction and shipbuilding sectors, previously reported, are confirmed by our analyses. Furthermore, data show that the annual percentage change is still growing: statistically significant increments in time trends are observed for 11 of 20 Italian regions. Of additional concern has been the identification of changes in 9 of 20 trends partially due to the misdiagnosis in the past.

CONCLUSIONS: Given the long latency of mesothelioma, preventive and legal measures with the ban of asbestos in Italy since 1992 are still not giving effects on mesothelioma mortality trends.}, } @article {pmid22726320, year = {2012}, author = {Park, EK and Takahashi, K and Jiang, Y and Movahed, M and Kameda, T}, title = {Elimination of asbestos use and asbestos-related diseases: an unfinished story.}, journal = {Cancer science}, volume = {103}, number = {10}, pages = {1751-1755}, pmid = {22726320}, issn = {1349-7006}, mesh = {Asbestos/*adverse effects/chemistry ; Asbestosis/etiology ; Carcinogens/chemistry/*toxicity ; Humans ; Neoplasms/etiology ; }, abstract = {Asbestos is a proven human carcinogen. Asbestos-related diseases (ARDs) typically comprise lung cancer, malignant mesothelioma, asbestosis, pleural plaques, thickening and effusion. International organizations, notably the World Health Organization and the International Labour Organization, have repeatedly declared the need to eliminate ARDs, and have called on countries to stop using asbestos. However, the relevant national-level indicators (e.g., incidence/mortality rates and per capita asbestos use, as well as their interrelationships) indicate that ARDs are increasing and asbestos use is continuing in the world. Lessons learned by industrialized countries in terms of policy and science have led to a growing number of countries adopting bans. In contrast, industrializing countries are faced with a myriad of forces prompting them to continue using asbestos. Full-scale international cooperation will thus be needed, with industrialized countries sharing their experiences and technologies to enable industrializing countries to make smooth transitions to banned states and achieve the goal of eliminating ARDs.}, } @article {pmid22722923, year = {2012}, author = {Elkiran, ET and Kaplan, MA and Sevinc, A and Aksoy, S and Demirci, U and Seker, M and Harputluoglu, H and Ozdemir, NY and Isik, F and Ulas, A and Inanc, M and Arslan, UY and Dogu, GG and Isikdogan, A and Buyukberber, S and , }, title = {Multicentric study on malignant pleural mesothelioma in Turkey: clinicopathologic and survival characteristics of 282 patients.}, journal = {Medical oncology (Northwood, London, England)}, volume = {29}, number = {5}, pages = {3147-3154}, pmid = {22722923}, issn = {1559-131X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use ; Combined Modality Therapy ; Female ; Humans ; Kaplan-Meier Estimate ; Male ; Mesothelioma/*mortality/*pathology/therapy ; Middle Aged ; Neoplasm Staging ; Pleural Neoplasms/*mortality/*pathology/therapy ; Radiotherapy ; Retrospective Studies ; Thoracic Surgical Procedures ; Treatment Outcome ; Turkey ; }, abstract = {Malignant pleural mesothelioma (MPM) is a relatively rare, but aggressive tumor that causes high mortality. The major risk factor involved in the etiology is environmental and occupational exposure to asbestos. The optimal modality of therapy is controversial. The present study retrospectively evaluated the data pertinent to 282 patients who were examined and treated in 11 different medical oncology centers in Turkey. There were 161 males (57.1 %) and 121 females (42.9 %), with a mean age of 56.38 ± 12.07 years. Surgery was used in 74 patients, 21 patients (28.4 %) received only chemotherapy and 28 patients (37.8 %) received chemoradiotherapy after surgery. The median survival in patients who were administered adjuvant therapy after surgery was 24 months, while the median survival in patients who had only surgery was 6 months (p = 0.029). 106 patients were administered pemetrexed-platinum combination and 35 patients were administered gemcitabine-platinum combination as front-line chemotherapy. Median survival, 1- and 2-year survival rates in patients who received platinum analogues and pemetrexed or gemcitabine combinations were found statistically similar (p = 0.15). The median survival for all patients with MPM in our study was 18 months. The main factors influencing the overall survival were stage of the disease (p = 0.020), performance status (p < 0.001), asbestos exposure (p = 0.030) and mesothelioma histological subtypes (p < 0.001). Results of our study suggest that multi-modality treatment regimens consisting of surgery, radiotherapy and chemotherapy prolong overall survival. Survival rates in patients who received combining platinum analogues with pemetrexed or gemcitabine as front-line chemotherapy were found similar.}, } @article {pmid22710676, year = {2012}, author = {Rushton, L and Hutchings, SJ and Fortunato, L and Young, C and Evans, GS and Brown, T and Bevan, R and Slack, R and Holmes, P and Bagga, S and Cherrie, JW and Van Tongeren, M}, title = {Occupational cancer burden in Great Britain.}, journal = {British journal of cancer}, volume = {107 Suppl 1}, number = {Suppl 1}, pages = {S3-7}, pmid = {22710676}, issn = {1532-1827}, mesh = {Adolescent ; Adult ; Aged ; Carcinogens ; Female ; Humans ; Male ; Middle Aged ; Neoplasms/*epidemiology/etiology ; Occupational Diseases/*epidemiology/etiology ; Occupational Exposure/*adverse effects ; United Kingdom/epidemiology ; Young Adult ; }, abstract = {A sound knowledge base is required to target resources to reduce workplace exposure to carcinogens. This project aimed to provide an objective estimate of the burden of cancer in Britain due to occupation. This volume presents extensive analyses for all carcinogens and occupational circumstances defined as definite or probable human occupational carcinogens by the International Agency for Research on Cancer. This article outlines the structure of the supplement - two methodological papers (statistical approach and exposure assessment), eight papers presenting the cancer-specific results grouped by broad anatomical site, a paper giving industry sector results and one discussing work-related cancer-prevention strategies. A brief summary of the methods and an overview of the updated overall results are given in this introductory paper. A general discussion of the overall strengths and limitations of the study is also presented. Overall, 8010 (5.3%) total cancer deaths in Britain and 13,598 cancer registrations were attributable to occupation in 2005 and 2004, respectively. The importance of cancer sites such as mesothelioma, sinonasal, lung, nasopharynx, breast, non-melanoma skin cancer, bladder, oesophagus, soft tissue sarcoma and stomach cancers are highlighted, as are carcinogens such as asbestos, mineral oils, solar radiation, silica, diesel engine exhaust, coal tars and pitches, dioxins, environmental tobacco smoke, radon, tetrachloroethylene, arsenic and strong inorganic mists, as well as occupational circumstances such as shift work and occupation as a painter or welder. The methods developed for this project are being adapted by other countries and extended to include social and economic impact evaluation.}, } @article {pmid22712847, year = {2012}, author = {Borelli, V and Trevisan, E and Vita, F and Bottin, C and Melato, M and Rizzardi, C and Zabucchi, G}, title = {Peroxidase-like activity of ferruginous bodies isolated by exploiting their magnetic property.}, journal = {Journal of toxicology and environmental health. Part A}, volume = {75}, number = {11}, pages = {603-623}, doi = {10.1080/15287394.2012.688478}, pmid = {22712847}, issn = {1528-7394}, mesh = {Air Pollutants, Occupational/*chemistry/isolation & purification/toxicity ; Asbestos/*chemistry/isolation & purification/toxicity ; Asbestosis/etiology/physiopathology ; Benzidines/*chemistry ; Catalysis ; Cell Line ; Chromogenic Compounds/*chemistry ; Cytotoxins/chemistry/isolation & purification/toxicity ; Ferric Compounds/*chemistry/toxicity ; Ferritins/chemistry/toxicity ; Ferrosoferric Oxide/chemistry/toxicity ; Humans ; Hydrogen-Ion Concentration ; Lung/chemistry/drug effects/pathology ; *Magnetic Phenomena ; Mesothelioma/chemistry/etiology/pathology ; Mineral Fibers/*analysis/toxicity ; Oxidation-Reduction ; Peroxidases/metabolism ; Respiratory Mucosa/chemistry/drug effects/pathology ; }, abstract = {Ferruginous bodies (FB) are polymorphic structures whose formation is macrophage dependent, and are composed of a core, which may consist of an asbestos fiber coated with proteins, among which ferritin is the main component. Within ferritin, the ferric and ferrous ions are coordinated as ferrihydrite, which is the main iron (Fe) storage compound. However, when ferritin accumulates in some tissues following Fe overload it also contains magnetite along with ferrihydrite, which endows it with magnetic properties. Recently studies showed that magnetite exerts peroxidase-like activity, and since ferruginous bodies display magnetic properties, it was postulated that these particular structures may also contain magnetite within the ferritin coating, and thus may also exert peroxidase-like activity. Histochemical analysis for peroxidase of isolated FB smears demonstrated positive staining. Samples isolated from 4 different autopsy lung fragments were also able to oxidize 3,3',5,5'-tetramethyl-benzidine to a blue colored compound that absorbs at 655 nm. This activity was (1) azide and heat insensitive with optimal pH from 5 to 6, and (2) highly variable, changing more than 25-fold from one sample to another. These findings, together with evidence that the peroxidase-like activity of ferruginous bodies has a hydrogen peroxide and substrate requirement different from that of human myeloperoxidase, can exclude that this enzyme gives a significant contribution to the formation of FB. Standard Fe-rich asbestos fibers also express a peroxidase-like activity, but this appears negligible compared to that of ferruginous bodies. Strong acidification of standard Fe-containing asbestos fibers or magnetically isolated ferruginous bodies liberates a high amount of peroxidase-like activity, which is probably accounted for by the release of Fe ions. Further, FB also damage mesothelial cells in vitro. Data suggest that FB exert peroxidase-like activity and cytotoxic activity against mesothelial cells, and hence may be an important factor in pathogenesis of asbestos-related diseases.}, } @article {pmid22710819, year = {2012}, author = {Ordóñez, NG}, title = {The use of immunohistochemistry in the diagnosis of composite and collision tumors: exemplified by pleural mesothelioma and carcinoid tumor of the lung.}, journal = {Applied immunohistochemistry & molecular morphology : AIMM}, volume = {20}, number = {4}, pages = {421-426}, doi = {10.1097/PAI.0b013e318238bb8f}, pmid = {22710819}, issn = {1533-4058}, mesh = {Aged ; Asbestos/adverse effects ; Carcinoid Tumor/*diagnosis/pathology/surgery ; Diagnosis, Differential ; Environmental Exposure/adverse effects ; Humans ; Immunohistochemistry/methods ; Lung/*pathology/surgery ; Lung Neoplasms/*diagnosis/pathology/surgery ; Lymphatic Metastasis ; Male ; Mesothelioma/*diagnosis/pathology/surgery ; Pleural Neoplasms/*diagnosis/pathology/surgery ; Pneumonectomy ; }, abstract = {A case of a collision lymph node metastasis of a mesothelioma and a carcinoid tumor in a 73-year-old man with a history of asbestos exposure is reported. An interesting finding in this case was that both the mesothelioma and its lymph node metastases exhibited a wide variety of histologic patterns, including one characterized by a solid growth of large cells with abundant, clear, and foamy cytoplasm and another exhibiting deciduoid features. Pathologists should be aware that mesotheliomas can present very unusual morphologic features, such as those seen in the present case, and therefore, should be included in the differential diagnosis of those tumors that can display similar morphology and can metastasize to the serosal membranes. Reexamination of the pneumonectomy specimen in the current case identified a primary peripheral carcinoid tumor. The recognition of a nonasbestos-related tumor in a patient with mesothelioma is important since its presence may have an impact on the patient's life expectancy and, therefore, may affect any compensation settlement.}, } @article {pmid22706369, year = {2012}, author = {Berrino, F and Bai, E}, title = {[Campaign «Asbestos free»].}, journal = {Epidemiologia e prevenzione}, volume = {36}, number = {2}, pages = {136-137}, pmid = {22706369}, issn = {1120-9763}, mesh = {Asbestos/*adverse effects ; Construction Materials ; Electric Wiring ; Environmental Exposure ; Female ; Geological Phenomena ; *Health Promotion ; Humans ; Italy ; Lung Neoplasms/epidemiology/etiology/prevention & control ; Male ; Mesothelioma/epidemiology/etiology/prevention & control ; Occupational Diseases/epidemiology/etiology/prevention & control ; Occupational Exposure ; Pleural Neoplasms/epidemiology/etiology/prevention & control ; Solar Energy ; }, } @article {pmid22692930, year = {2012}, author = {Bonneterre, V and Mathern, G and Pelen, O and Balthazard, AL and Delafosse, P and Mitton, N and Colonna, M}, title = {Cancer incidence in a chlorochemical plant in Isère, France: an occupational cohort study, 1979-2002.}, journal = {American journal of industrial medicine}, volume = {55}, number = {9}, pages = {756-767}, doi = {10.1002/ajim.22069}, pmid = {22692930}, issn = {1097-0274}, mesh = {Asbestos/adverse effects ; Carcinogens, Environmental/*adverse effects ; *Chemical Industry ; Chlorine/*adverse effects ; Cohort Studies ; Dioxins/adverse effects ; France/epidemiology ; Humans ; Hydrocarbons, Chlorinated/*adverse effects ; Incidence ; Male ; Mesothelioma/chemically induced/epidemiology ; Neoplasms/*chemically induced/epidemiology ; Occupational Diseases/*chemically induced/epidemiology ; Occupational Exposure/*adverse effects/statistics & numerical data ; Pleural Neoplasms/chemically induced/epidemiology ; Registries ; Surveys and Questionnaires ; Urinary Bladder Neoplasms/chemically induced/epidemiology ; }, abstract = {BACKGROUND: A major French chlorine chemical plant (chlor-alkali process with diaphragm cell and manufacturing of organochlorine chemicals) has used or produced known or suspected carcinogenic compounds.

METHODS: A cohort study, based on the plant occupational health service and the regional cancer registry, analyzed the standardized incidence ratios of malignant tumors for the period 1979-2002. Individual exposures were estimated from workers' occupational histories in a dual division of jobs into 9 sectors and 115 workshops with known exposures.

RESULTS: Men (2,742) were followed, corresponding to 52,794 person-years. Primary tumors (304) were observed for 290 expected cases, a non-significant 5% excess. A significant excess was found of pleural mesothelioma and bladder cancer in employees hired before 1964.

CONCLUSION: Excesses of mesothelioma and bladder cancer were found, whereas there was no excess of hematopoietic cancers despite high benzene and dioxin exposures. Surprisingly, mesothelioma cases did not include workers who were the most exposed to asbestos.}, } @article {pmid22691906, year = {2012}, author = {Lazarus, A and Massoumi, A and Hostler, J and Hostler, DC}, title = {Asbestos-related pleuropulmonary diseases: benign and malignant.}, journal = {Postgraduate medicine}, volume = {124}, number = {3}, pages = {116-130}, doi = {10.3810/pgm.2012.05.2555}, pmid = {22691906}, issn = {1941-9260}, mesh = {Asbestos/*toxicity ; Asbestosis/diagnosis/*pathology/prevention & control ; Biomarkers/blood ; Humans ; Lung Diseases/*chemically induced/diagnosis/*pathology/prevention & control ; Mesothelioma/*chemically induced/diagnosis/*pathology/prevention & control ; Pleural Diseases/*chemically induced/diagnosis/*pathology/prevention & control ; Prognosis ; }, abstract = {Asbestos is known for its desirable properties of thermal and heat resistance along with excellent strength and durability. It was widely used in many industries since the late 19th century, until its adverse effects on health were recognized. The occurrence of pleuropulmonary changes from exposure to asbestos often has a latency period of 20 to 30 years. The use of asbestos has been banned, regulated, and minimized in many countries, but in several developing countries, the use of asbestos in industries is still a common practice. In this article, the benign and malignant clinical manifestations of asbestos exposure are discussed.}, } @article {pmid22684220, year = {2012}, author = {Ordóñez, NG}, title = {Deciduoid mesothelioma: report of 21 cases with review of the literature.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {25}, number = {11}, pages = {1481-1495}, doi = {10.1038/modpathol.2012.105}, pmid = {22684220}, issn = {1530-0285}, mesh = {Adolescent ; Adult ; Aged ; Biomarkers, Tumor/analysis ; Cell Shape ; Cell Size ; Diagnosis, Differential ; *Epithelioid Cells/chemistry/ultrastructure ; Female ; Humans ; Immunohistochemistry ; Male ; *Mesothelioma/chemistry/mortality/therapy/ultrastructure ; Microscopy, Electron ; Middle Aged ; Mitotic Index ; Neoplasm Grading ; *Peritoneal Neoplasms/chemistry/mortality/therapy/ultrastructure ; *Pleural Neoplasms/chemistry/mortality/therapy/ultrastructure ; Predictive Value of Tests ; Survival Analysis ; Time Factors ; Treatment Outcome ; Young Adult ; }, abstract = {Deciduoid mesothelioma is a rare variant of epithelioid mesothelioma that was initially considered to occur exclusively in the peritoneum of young women who had no history of asbestos exposure and to be characterized by an aggressive clinical course, but it was later demonstrated that this tumor could also occur in the pleura of older men and women who had been exposed to asbestos. Some subsequent studies have also indicated that the clinical course is no different from that of conventional epithelioid mesothelioma. Herein are reported 21 cases of deciduoid mesothelioma that were investigated using a large panel of immunohistochemical markers, 9 of which were also studied by electron microscopy. Fifteen of the patients were male and 6 were female (mean age, 60 years). Seventeen of the cases originated in the pleura and four in the peritoneum. Histologically, all of the cases were composed of large, polygonal or ovoid cells with well-defined cell borders, dense eosinophilic cytoplasm, and single or multiple nuclei. In some cases, the cells exhibited a wide variation in their size and shape, frequent loss of cell cohesion, marked nuclear atypia, and high mitotic activity (>5 per 10 HPF); whereas, in others, the cells were more cohesive, less pleomorphic, and the mitotic activity low. As the survival of patients in the first group of cases was shorter (mean, 7 months), when compared with that of the latter (mean, 23 months), it is concluded that the differences in prognosis reported in deciduoid mesothelioma are due to the existence of a high-grade subgroup that presents highly aggressive clinical behavior. Therefore, when a high-grade deciduoid mesothelioma is present, it should be reported as it can significantly affect prognosis and treatment. The use of immunohistochemistry and electron microscopy in assisting in the differential diagnosis of deciduoid mesothelioma is also discussed.}, } @article {pmid22677986, year = {2012}, author = {Comar, M and Zanotta, N and Pesel, G and Visconti, P and Maestri, I and Rinaldi, R and Crovella, S and Cortale, M and De Zotti, R and Bovenzi, M}, title = {Asbestos and SV40 in malignant pleural mesothelioma from a hyperendemic area of north-eastern Italy.}, journal = {Tumori}, volume = {98}, number = {2}, pages = {210-214}, doi = {10.1177/030089161209800205}, pmid = {22677986}, issn = {2038-2529}, mesh = {Adult ; Aged ; Asbestos/*toxicity ; Carcinogens/*toxicity ; DNA, Viral/isolation & purification ; Disease Susceptibility ; Endemic Diseases ; Female ; Humans ; Italy/epidemiology ; Male ; Mesothelioma/chemically induced/*epidemiology/*etiology/virology ; Middle Aged ; Pleural Neoplasms/chemically induced/*epidemiology/*etiology/virology ; Polyomavirus Infections/*complications/virology ; Real-Time Polymerase Chain Reaction ; Risk Factors ; *Simian virus 40/isolation & purification ; Tumor Virus Infections/*complications/virology ; Viral Load ; }, abstract = {AIMS AND BACKGROUND: Malignant mesothelioma is a fatal cancer of increasing incidence in north-eastern Italy. Together with asbestos, the polyomavirus SV40 was hypothesized to contribute to the onset of malignant mesothelioma. To investigate the putative role of SV40 in the individual susceptibility to asbestos-induced malignant mesothelioma, we conducted a molecular epidemiological study on a series of malignant mesothelioma patients from an area in north-eastern Italy hyperendemic for malignant pleural mesothelioma.

METHODS AND STUDY DESIGN: We collected 63 mesothelioma samples from incidence cases of patients diagnosed with malignant pleural mesothelioma in the period 2009-2010. DNA was extracted from patients' tissue biopsies using the BioRobot EZ1 Qiagen workstation. SV40 sequence detection and quantification was performed by specific real time PCR. The 74.6% of the 63 enrolled patients had a history of asbestos exposure. The epithelioid histotype was more prevalent in males (64.0%) and the mixed in females (61.5%) who showed significantly higher cancer co-morbidity (46.1% vs 12%, P = 0.005). SV40 was detected in 22% of MM tumors, with a low viral load. In SV40-positive patients, a threefold increased risk of asbestos exposure was observed, more evident in females (OR 4.32) than in males (OR 1.20).

CONCLUSIONS: Our findings indicate that a high prevalence of SV40 was present in malignant mesothelioma incident cases from an area hyperendemic for malignant mesothelioma in north-eastern Italy. Although asbestos is considered the main risk factor in malignant mesothelioma onset, a role for SV40 could be hypothesized.}, } @article {pmid22668748, year = {2012}, author = {Finley, BL and Pierce, JS and Paustenbach, DJ and Scott, LL and Lievense, L and Scott, PK and Galbraith, DA}, title = {Malignant pleural mesothelioma in US automotive mechanics: reported vs expected number of cases from 1975 to 2007.}, journal = {Regulatory toxicology and pharmacology : RTP}, volume = {64}, number = {1}, pages = {104-116}, doi = {10.1016/j.yrtph.2012.05.015}, pmid = {22668748}, issn = {1096-0295}, mesh = {Asbestos, Serpentine/*adverse effects ; Female ; Humans ; Male ; Mesothelioma/diagnosis/*epidemiology/etiology ; Occupational Exposure/*adverse effects/statistics & numerical data ; Pleural Neoplasms/diagnosis/*epidemiology/etiology ; United States/epidemiology ; *Work/statistics & numerical data/trends ; }, abstract = {Until the 1980s, chrysotile asbestos was a component of automotive brakes manufactured in the US. The current OSHA Bulletin (2006) for brake repair cites a single study (Lemen, 2004) which concluded that the number of mesothelioma cases reported in the literature in "end-product users of friction materials" indicated an asbestos-related risk for auto mechanics. However, Lemen (2004) did not compare the reported number of cases to an "expected" value, even though pleural mesothelioma occurs in the general population in the absence of asbestos exposure. We compare the number of malignant pleural mesothelioma (MPM) cases reported in the US literature among auto mechanics between 1975-2007 to an expected value derived from estimated numbers of current and former auto mechanics. A total of 106 cases categorized as mesothelioma or malignant neoplasm of the pleura were found in the literature. Using background incidence rates for MPM of two and three cases per million individuals per year, we estimated that a range of 278-515 cases of non-asbestos-related MPM, respectively, would have occurred in current or former auto mechanics from 1975-2007. Our findings are consistent with the numerous epidemiology studies that have found no increased risk of MPM in auto mechanics.}, } @article {pmid22658812, year = {2013}, author = {Kao, SC and Vardy, J and Chatfield, M and Corte, P and Pavlakis, N and Clarke, C and van Zandwijk, N and Clarke, S}, title = {Validation of prognostic factors in malignant pleural mesothelioma: a retrospective analysis of data from patients seeking compensation from the New South Wales Dust Diseases Board.}, journal = {Clinical lung cancer}, volume = {14}, number = {1}, pages = {70-77}, doi = {10.1016/j.cllc.2012.03.011}, pmid = {22658812}, issn = {1938-0690}, mesh = {Age Factors ; Aged ; Aged, 80 and over ; Female ; Hemoglobins/metabolism ; Humans ; Kaplan-Meier Estimate ; Lymphocyte Count ; Lymphocytes ; Male ; Mesothelioma/drug therapy/*pathology ; Middle Aged ; Multivariate Analysis ; Neoplasm Staging ; Neutrophils ; New South Wales ; Platelet Count ; Pleural Neoplasms/drug therapy/*pathology ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; }, abstract = {INTRODUCTION: We aimed to examine the prognostic values of established risk factors and to validate the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in an independent series of patients with malignant pleural mesothelioma (MPM).

PATIENTS AND METHODS: A total of 148 patients who applied for compensation at the Dust Diseases Board from 2007 to 2009 were included in this study. Overall survival was determined by the Kaplan-Meier method, and NLR was defined as the absolute neutrophil divided by the lymphocyte count. The prognostic value of the variables was examined by using Cox regression analysis, and all factors were entered into a multivariate model to determine their independent effect.

RESULTS: The patient characteristics were median age of 73 years; 93% men; 59% epithelial subtype; median NLR of 3.5 at diagnosis (n = 79); median overall survival of 10.6 months. The following variables were predictive of longer overall survival in univariate analysis: younger age, epithelial subtype, lower tumor stage, low white cell count, low platelet count, low hemoglobin level, and low NLR. Multivariate analysis confirmed that nonepithelial vs. epithelial subtype (hazard ratio [HR], 3.0; P < .001), tumor stage (HR, 1.6; P < .001), hemoglobin level difference ≥10 vs. <10 (HR, 2.0; P = .03), no chemotherapy vs. use of chemotherapy (HR, 2.4; P < .001), and NLR ≥3 vs. <3 (HR, 2.2; P < .01) were independently associated with prognosis.

CONCLUSIONS: Apart from previously recognized factors, such as histosubtype, tumor stage, and hemoglobin level difference, NLR, an index of systemic inflammation bears prognostic significance that shows that a snapshot of immune status is able to convey important prognostic information.}, } @article {pmid22644408, year = {2013}, author = {Andersson, E and Westberg, H and Bryngelsson, IL and Magnuson, A and Persson, B}, title = {Cancer incidence among Swedish pulp and paper mill workers: a cohort study of sulphate and sulphite mills.}, journal = {International archives of occupational and environmental health}, volume = {86}, number = {5}, pages = {529-540}, pmid = {22644408}, issn = {1432-1246}, mesh = {Adult ; *Carcinogens ; Cohort Studies ; Female ; Follow-Up Studies ; Humans ; Incidence ; Male ; Neoplasms/epidemiology/*etiology ; Occupational Diseases/epidemiology/*etiology ; Occupational Exposure/*adverse effects/analysis/statistics & numerical data ; *Paper ; Risk Factors ; Sex Factors ; Sulfates/*adverse effects ; Sulfites/*adverse effects ; Sweden/epidemiology ; }, abstract = {PURPOSE: Associations between various malignancies and work in the pulp and paper industry have been reported but mostly in analyses of mortality rather than incidence. We aimed to study cancer incidence by main mill pulping process, department and gender in a Swedish cohort of pulp and paper mill workers.

METHODS: The cohort (18,113 males and 2,292 females, enrolled from 1939 to 1999 with >1 year of employment) was followed up for cancer incidence from 1958 to 2001. Information on the workers' department and employment was obtained from the mills' personnel files, and standardized incidence ratios (SIRs) were calculated using the Swedish population as reference.

RESULTS: Overall cancer incidence, in total 2,488 cases, was not increased by work in any department. However, risks of pleural mesothelioma were increased among males employed in sulphate pulping (SIR, 8.38; 95 % CI, 3.37-17) and maintenance (SIR, 6.35; 95 % CI, 3.47-11), with no corresponding increase of lung cancer. Testicular cancer risks were increased among males employed in sulphate pulping (SIR, 4.14; 95 % CI, 1.99-7.61) and sulphite pulping (SIR, 2.59; 95 % CI, 0.95-5.64). Female paper production workers showed increased risk of skin tumours other than malignant melanoma (SIR, 2.92; 95 % CI, 1.18-6.02).

CONCLUSIONS: Incidence of pleural mesothelioma was increased in the cohort, showing that asbestos exposure still has severe health consequences, and highlighting the exigency of strict asbestos regulations and elimination. Testicular cancer was increased among pulping department workers. Shift work and endocrine disruptors could be of interest in this context.}, } @article {pmid22644294, year = {2012}, author = {van der Bij, S and Koffijberg, H and Burgers, JA and Baas, P and van de Vijver, MJ and de Mol, BA and Moons, KG}, title = {Prognosis and prognostic factors of patients with mesothelioma: a population-based study.}, journal = {British journal of cancer}, volume = {107}, number = {1}, pages = {161-164}, pmid = {22644294}, issn = {1532-1827}, mesh = {Age Factors ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Mesothelioma/*diagnosis/mortality ; Middle Aged ; Netherlands/epidemiology ; Pleural Neoplasms/diagnosis/mortality ; Population Surveillance ; Prognosis ; Risk Factors ; Survival Analysis ; }, abstract = {BACKGROUND: It is important to regularly update survival estimates of patients with malignant mesothelioma as prognosis may vary according to epidemiologic factors and diagnostic and therapeutic management.

METHODS: We assessed overall (baseline) survival as well as related prognostic variables in a large cohort of 1353 patients with a confirmed diagnosis of malignant mesothelioma between 2005 and 2008.

RESULTS: About 50% of the patients were 70 years or older at diagnosis and the median latency time since start of asbestos exposure was 49 years. One year after diagnosis, 47% of the patients were alive, 20% after 2 years and 15% after 3 years. Prognostic variables independently associated with worse survival were: older age (HR=1.04 per year 95% CI (1.03-1.06)), sarcomatoid subtype (HR=2.45 95% CI (2.06-2.90)) and non-pleural localisation (HR=1.67 95% CI (1.26-2.22)).

CONCLUSION: Survival of patients with malignant mesothelioma is still limited and depends highly on patient age, mesothelioma subtype and localisation. In addition, a substantial part of the patients had a long latency time between asbestos exposure and diagnosis.}, } @article {pmid22642290, year = {2012}, author = {Walker, AM and Maxim, LD and Utell, MJ}, title = {Are airborne refractory ceramic fibers similar to asbestos in their carcinogenicity?.}, journal = {Inhalation toxicology}, volume = {24}, number = {7}, pages = {416-424}, doi = {10.3109/08958378.2012.683892}, pmid = {22642290}, issn = {1091-7691}, mesh = {Adult ; Aged ; Aged, 80 and over ; Air Pollutants, Occupational/*toxicity ; Asbestos/toxicity ; Carcinogens/toxicity ; Ceramics/*toxicity ; Humans ; Lung Neoplasms/*chemically induced/epidemiology ; Male ; Mesothelioma/*chemically induced/epidemiology ; Middle Aged ; Mineral Fibers/*toxicity ; Occupational Diseases/*chemically induced/epidemiology ; Occupational Exposure/adverse effects ; }, abstract = {BACKGROUND: Animal studies on refractory ceramic fiber (RCF) have led to the suggestion that RCF might resemble asbestos in carcinogenicity. Human data are available to test this hypothesis.

METHODS: We compared the occurrence of lung cancer and mesothelioma in 605 men engaged in the manufacture of RCF and followed since 1987 to cancer rates that would have been anticipated if airborne RCF were carcinogenic to the same degree as are crocidolite, amosite or chrysotile asbestos. We integrated the results of workplace exposure monitoring with mortality follow-up using formulas presented by Hodgson and Darnton (2000) to estimate hypothesized risks under different asbestos scenarios.

RESULTS: During 15,281 person-years of observation, there were 12 deaths from lung cancer. General population rates predicted 11.8 cases expected for an observed/expected (O/E) ratio of 1.0. Anticipated numbers of deaths from lung cancer under hypotheses of carcinogenicity similar to that of amphiboles and chrysotile were 62 and 17, allowing for rejection of amphibole-like effects (p < 10(-5)) but not chrysotile-like carcinogenicity (p = 0.15). There were no cases of mesothelioma, as compared to 4.9 anticipated under a crocidolite-like hypothesis (p = 0.007 to reject), 1.0 for amosite (p = 0.38) and 0.05 for chrysotile (p = 0.95).

CONCLUSION: There was no increase in lung cancer or mesothelioma in these workers exposed to RCF. If the cohort had the same exposure to crocidolite asbestos the number of lung cancer and mesothelioma cases would have been significantly greater than observed. The data do not yet permit a similar conclusion with respect to chrysotile asbestos.}, } @article {pmid22622048, year = {2012}, author = {Rascoe, PA and Jupiter, D and Cao, X and Littlejohn, JE and Smythe, WR}, title = {Molecular pathogenesis of malignant mesothelioma.}, journal = {Expert reviews in molecular medicine}, volume = {14}, number = {}, pages = {e12}, doi = {10.1017/erm.2012.6}, pmid = {22622048}, issn = {1462-3994}, mesh = {Animals ; Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Apoptosis/drug effects ; Humans ; Mesothelioma/drug therapy/etiology/*genetics/*pathology ; bcl-X Protein/antagonists & inhibitors/genetics/metabolism ; }, abstract = {Malignant mesothelioma is a rare, highly aggressive cancer arising from mesothelial cells that line the pleural cavities. Approximately 80% of mesothelioma cases can be directly attributed to asbestos exposure. Additional suspected causes or co-carcinogens include other mineral fibres, simian virus 40 (SV40) and radiation. A mesothelioma epidemic in Turkey has demonstrated a probable genetic predisposition to mineral fibre carcinogenesis and studies of human tissues and animal models of mesothelioma have demonstrated genetic and epigenetic events that contribute to the multistep process of mineral fibre carcinogenesis. Several growth factors and their receptors have a significant role in the oncogenesis, progression and resistance to therapy of mesothelioma. Epidermal growth factor (EGF), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF) and insulin-like growth factor (IGF) have been shown as targets for therapy based on promising preclinical data. However, clinical trials of tyrosine kinase inhibitors in mesothelioma have been disappointing. Bcl-XL is an important antiapoptotic member of the Bcl-2 family and is overexpressed in several solid tumours, including mesothelioma. Reduction of Bcl-XL expression in mesothelioma induces apoptosis and engenders sensitisation to cytotoxic chemotherapeutic agents. Pharmacological inhibitors of antiapoptotic Bcl-2 family members continue to undergo refinement and have shown promise in mesothelioma.}, } @article {pmid22617814, year = {2012}, author = {Myers, R}, title = {Asbestos-related pleural disease.}, journal = {Current opinion in pulmonary medicine}, volume = {18}, number = {4}, pages = {377-381}, doi = {10.1097/MCP.0b013e328354acfe}, pmid = {22617814}, issn = {1531-6971}, mesh = {Asbestos/*toxicity ; Humans ; Inhalation Exposure/*adverse effects ; Mesothelioma/*diagnosis/etiology/physiopathology ; Pleural Diseases/*diagnosis/etiology/physiopathology ; }, abstract = {PURPOSE OF REVIEW: Asbestos exposure is the cause of significant pleural disease - both benign and malignant. Although there is increased awareness, individuals continue to be exposed, and we will continue to see its sequelae for years to come because of the delay between exposure and disease manifestation. Asbestos-related pleural disease includes pleural plaques, diffuse pleural thickening, benign asbestos-related pleural effusions (BAPEs), and malignant pleural mesothelioma (MPM).

RECENT FINDINGS: Several recent studies are highlighted throughout this review, including a comparative analysis of diagnostic imaging modalities for identifying and characterizing pleural plaques, the effect of pleural plaques on lung volumes and flows, and how pain is a relatively common feature in patients with pleural plaques. Advances in the treatment of MPM are limited, but a recent publication highlights the increased morbidity associated with surgical debulking procedures and questions the benefit of these procedures.

SUMMARY: Asbestos-related pleural disease will continue to present a significant burden of illness. Recent publications have suggested potential treatment benefit and point to areas that would require further investigation.}, } @article {pmid22617246, year = {2012}, author = {Kirschner, MB and Cheng, YY and Badrian, B and Kao, SC and Creaney, J and Edelman, JJ and Armstrong, NJ and Vallely, MP and Musk, AW and Robinson, BW and McCaughan, BC and Klebe, S and Mutsaers, SE and van Zandwijk, N and Reid, G}, title = {Increased circulating miR-625-3p: a potential biomarker for patients with malignant pleural mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {7}, number = {7}, pages = {1184-1191}, doi = {10.1097/JTO.0b013e3182572e83}, pmid = {22617246}, issn = {1556-1380}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/blood/*genetics ; Case-Control Studies ; Female ; Gene Expression Profiling ; Humans ; Male ; Mesothelioma/*blood/diagnosis/*genetics ; MicroRNAs/blood/*genetics ; Middle Aged ; Pleural Neoplasms/*blood/diagnosis/*genetics ; Prognosis ; Real-Time Polymerase Chain Reaction ; Young Adult ; }, abstract = {INTRODUCTION: We investigated the ability of cell-free microRNAs (miRNAs) in plasma and serum to serve as a biomarker for malignant mesothelioma (MM).

METHODS: Using miRNA microarrays, we profiled plasma samples from MM patients and healthy controls. miRNAs with significantly different abundance between cases and controls were validated in a larger series of MM patients and in an independent series of MM patients using quantitative real-time polymerase chain reaction. Levels of candidate miRNAs were also quantified in MM tumor samples.

RESULTS: We compared cell-free miRNA profiles in plasma from MM patients with healthy controls. Reviewing 90 miRNAs previously reported to be associated with MM, we found that the levels of two miRNAs, miR-29c* and miR-92a, were elevated in plasma samples from MM patients. In addition, we identified 15 novel miRNAs present at significantly higher levels in the plasma of MM patients. Further analysis of candidate miRNAs by real time-quantitative polymerase chain reaction confirmed that one of them, miR-625-3p, was present in significantly higher concentration in plasma/serum from MM patients and was able to discriminate between cases and controls, in both the original and the independent series of patients. MiR-625-3p was also found to be up-regulated in tumor specimens from a group of 18 MM patients, who underwent extrapleural pneumonectomy.

CONCLUSION: Our data confirm the potential of miR-29c* and miR-92a as candidate tumor markers and reveal that miR-625-3p is a promising novel diagnostic marker for MM.}, } @article {pmid22617242, year = {2012}, author = {Lin, S and Wang, X and Yu, IT and Yano, E and Courtice, M and Qiu, H and Wang, M}, title = {Cause-specific mortality in relation to chrysotile-asbestos exposure in a Chinese cohort.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {7}, number = {7}, pages = {1109-1114}, doi = {10.1097/JTO.0b013e3182519a60}, pmid = {22617242}, issn = {1556-1380}, mesh = {Adult ; Asbestos, Serpentine/*adverse effects ; China/epidemiology ; Female ; Follow-Up Studies ; Humans ; Incidence ; Male ; Middle Aged ; Neoplasms/*chemically induced/epidemiology/*mortality ; Occupational Diseases/*chemically induced/epidemiology/*mortality ; Occupational Exposure/*adverse effects ; Prognosis ; Prospective Studies ; Smoking/adverse effects/mortality ; Survival Rate ; }, abstract = {INTRODUCTION: The carcinogenic potency of chrysotile asbestos remains a contentious topic, and more data are needed to address this issue. We examine cause-specific mortality, especially lung cancer, and its association with chrysotile-asbestos exposure in a Chinese cohort.

METHODS: A cohort of 577 workers from a chrysotile-textile plant was followed prospectively from 1972 to 2008. Occupational history, exposure information, and smoking data were obtained from company records and personal interviews; vital status and causes of death were ascertained from death registries and hospitals. Workers were classified into three exposure levels on the basis of exposure assessments of different workshops. Standardized Mortality Ratios (SMRs) were calculated in terms of exposure levels and other indices.

RESULTS: Among 259 identified deaths, 53 died from lung cancer, with an SMR of 4.08 (95% confidence interval 3.12, 5.33), and 96 from all cancers with an SMR of 2.09 (1.71, 2.55). In addition, two deaths from mesothelioma were observed. Increased mortality from respiratory diseases was also observed (SMR 3.38, 95% confidence interval 2.72, 4.21). Asbestos-exposure levels, exposure years, and birth cohorts showed a clear trend of risk for lung cancer and respiratory diseases.

CONCLUSION: The current analysis indicated that exposure to chrysotile asbestos was closely associated with excess mortality from lung cancer and respiratory diseases.}, } @article {pmid22608353, year = {2012}, author = {Metintas, M and Ak, G and Cadirci, O and Yildirim, H and Dundar, E and Metintas, S}, title = {Outcome of patients diagnosed with fibrinous pleuritis after medical thoracoscopy.}, journal = {Respiratory medicine}, volume = {106}, number = {8}, pages = {1177-1183}, doi = {10.1016/j.rmed.2012.04.009}, pmid = {22608353}, issn = {1532-3064}, mesh = {Aged ; Asbestos/adverse effects ; Diagnosis, Differential ; False Negative Reactions ; Female ; Follow-Up Studies ; Humans ; Male ; Mesothelioma/diagnosis/etiology ; Middle Aged ; Pleural Effusion, Malignant/diagnosis ; Pleural Neoplasms/diagnosis/etiology ; Pleurisy/*diagnosis ; Risk Factors ; Sex Factors ; Smoking/adverse effects ; Thoracoscopy/*methods ; Tomography, X-Ray Computed ; }, abstract = {BACKGROUND: In patients with post- medical thoracoscopy histopathological diagnoses of fibrinous pleuritis, confusion can occur concerning subsequent procedures. This issue is particularly important in regions where mesothelioma is prevalent. We aimed to identify false negatives among patients where mesothelioma was common due to asbestos exposure whose histopathological diagnosis following thoracoscopy was fibrinous pleuritis. We also determined risk factors associated with patients that required additional advanced invasive procedures for diagnosis.

METHODS: Overall, 287 patients who underwent thoracoscopy were included in the study. Patients diagnosed with fibrinous pleuritis as a result of thoracoscopy were followed for 2 years regarding this condition. More invasive procedures were performed on patients who showed no recuperation or developed pleural disease again during the follow-up period.

RESULTS: Fibrinous pleuritis was observed in 101 (35.2%) patients. Follow-up of these patients revealed that the false negative rate was 18% for malignant pleural diseases. The thoracoscopist's opinion regarding the pleural space, computed tomography scan findings indicating malignancy, pain and female gender were determined to be risk factors for malignant pleural diseases.

CONCLUSIONS: In regions where mesothelioma is prevalent and one of the above-stated risk factors is present, patients whose post-thoracoscopy histopathological diagnosis is fibrinous pleuritis should be treated with a more advanced invasive diagnosis procedure.}, } @article {pmid22607943, year = {2012}, author = {Doo, SW and Cho, KH and Kim, JS and Yang, WJ and Choi, IH and Lee, DW and Hong, SS and Song, YS}, title = {Radiologic findings of mesothelioma at the tunica vaginalis.}, journal = {Urology}, volume = {80}, number = {1}, pages = {e3-5}, doi = {10.1016/j.urology.2012.02.050}, pmid = {22607943}, issn = {1527-9995}, mesh = {Adult ; Humans ; Male ; Mesothelioma/*diagnosis/diagnostic imaging ; Testicular Neoplasms/*diagnosis/diagnostic imaging ; Tomography, X-Ray Computed ; Ultrasonography ; }, abstract = {Malignant mesothelioma of the tunica vaginalis testis is a rare, but often fatal, malignancy that usually appears during the fourth decade and has a strong relationship with occupational exposure to asbestos and long-lasting hydrocele. We present a case involving a 36-year-old man without a history of hydrocele, trauma, or exposure to asbestos who developed malignant mesothelioma.}, } @article {pmid22584686, year = {2012}, author = {Schinwald, A and Murphy, FA and Prina-Mello, A and Poland, CA and Byrne, F and Movia, D and Glass, JR and Dickerson, JC and Schultz, DA and Jeffree, CE and Macnee, W and Donaldson, K}, title = {The threshold length for fiber-induced acute pleural inflammation: shedding light on the early events in asbestos-induced mesothelioma.}, journal = {Toxicological sciences : an official journal of the Society of Toxicology}, volume = {128}, number = {2}, pages = {461-470}, doi = {10.1093/toxsci/kfs171}, pmid = {22584686}, issn = {1096-0929}, support = {G0901697/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; Asbestos/*toxicity ; Female ; Mesothelioma/*chemically induced ; Metals/toxicity ; Mice ; Mice, Inbred C57BL ; Microscopy, Electron, Scanning ; Nanofibers/*toxicity ; Phagocytosis ; Pleurisy/*chemically induced ; }, abstract = {Suspicion has been raised that high aspect ratio nanoparticles or nanofibers might possess asbestos-like pathogenicity. The pleural space is a specific target for disease in individuals exposed to asbestos and by implication of nanofibers. Pleural effects of fibers depends on fiber length, but the key threshold length beyond which adverse effects occur has never been identified till now because all asbestos and vitreous fiber samples are heterogeneously distributed in their length. Nanotechnology advantageously allows for highly defined length distribution of synthetically engineered fibers that enable for in-depth investigation of this threshold length. We utilized the ability to prepare silver nanofibers of five defined length classes to demonstrate a threshold fiber length for acute pleural inflammation. Nickel nanofibers and carbon nanotubes were then used to strengthen the relationship between fiber length and pleural inflammation. A method of intrapleural injection of nanofibers in female C57Bl/6 strain mice was used to deliver the fiber dose, and we then assessed the acute pleural inflammatory response. Chest wall sections were examined by light and scanning electron microscopy to identify areas of lesion; furthermore, cell-nanowires interaction on the mesothelial surface of the parietal pleura in vivo was investigated. Our results showed a clear threshold effect, demonstrating that fibers beyond 4 µm in length are pathogenic to the pleura. The identification of the threshold length for nanofiber-induced pathogenicity in the pleura has important implications for understanding the structure-toxicity relationship for asbestos-induced mesothelioma and consequent risk assessment with the aim to contribute to the engineering of synthetic nanofibers by the adoption of a benign-by-design approach.}, } @article {pmid22580886, year = {2012}, author = {Helmig, S and Grossmann, M and Wübbeling, J and Schneider, J}, title = {Interleukin gene polymorphisms in pneumoconiosis.}, journal = {International journal of molecular medicine}, volume = {30}, number = {2}, pages = {401-408}, doi = {10.3892/ijmm.2012.996}, pmid = {22580886}, issn = {1791-244X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Alleles ; Case-Control Studies ; Genotype ; Germany ; Humans ; Inflammation Mediators ; Interleukins/*genetics ; Lung Diseases/complications/genetics ; Middle Aged ; Pneumoconiosis/epidemiology/etiology/*genetics ; *Polymorphism, Genetic ; Young Adult ; }, abstract = {Inhaled asbestos fibres are known to cause inflammation processes with the result of lung or pleural fibrosis and malignancies. Interleukins (IL), such as IL-1β, IL-6 and IL-10, have various functions in the regulation of the inflammatory response and in proliferative processes after inhalation of silica dust and can, therefore, influence the pathogenesis of asbestos-induced fibrosis and carcinogenesis. Polymorphisms within these genes may be associated with susceptibility to silica and asbestos-induced lung diseases. Thus, IL-1β, IL-6 and IL-10 polymorphisms were examined to determine an association with asbestos or silica-induced fibrosis or malignancies. Association studies were performed in 1180 individuals, using control subjects (n=177), fibrosis patients (n=605), lung cancer (LC) patients (n=364) and malignant mesothelioma (MM) patients (n=34). IL-1β (C-511T; C+3954T), IL-6 (G-174C) as well as IL-10 (G-1082A) polymorphisms were investigated. Compared to a healthy (control) group, a higher risk was seen for malignant mesothelioma patients in all investigated polymorphisms. The IL-6 -174C allele showed a tendency towards a higher risk for fibrosis or asbestos-induced lung cancer (ORasbestosis, 1.338; 95% CI, 0.71-2.53; ORsilicosis, 1.226; 95% CI, 0.54-2.81; ORfibrosis other aetiology, 1.313; 95% CI, 0.58-2.98 and ORLC asbestos, 2.112; 95% CI, 0.75-5.92). The IL-10 -1082A carrier seemed to be at higher risk for silicosis (ORsilicosis, 2.064; 95% CI, 0.78-5.49) but not for asbestosis. In summary, this study did not reveal sufficient evidence for a significant association of the investigated interleukin polymorphisms with asbestos or silica-induced diseases in the population studied.}, } @article {pmid22576381, year = {2012}, author = {Hayashi, K and Takamura, M and Sato, Y and Takahashi, K and Sato, H and Youkou, K and Yokoyama, H and Nomoto, M and Inoue, C and Hasegawa, G and Aoyagi, Y}, title = {Primary malignant mesothelioma of the appendix.}, journal = {Internal medicine (Tokyo, Japan)}, volume = {51}, number = {9}, pages = {1027-1030}, doi = {10.2169/internalmedicine.51.6990}, pmid = {22576381}, issn = {1349-7235}, mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage ; Appendiceal Neoplasms/*diagnosis/drug therapy ; Fatal Outcome ; Humans ; Male ; Mesothelioma/*diagnosis/drug therapy ; }, abstract = {We report a case of primary malignant mesothelioma of the appendix. A 35-year-old man without any history of asbestos exposure was admitted to our hospital for further examination following the discovery of multiple liver tumors, an ileocecal tumor, and abdominal lymph node swelling. An ultrasound-guided liver tumor biopsy revealed malignant mesothelioma. Despite receiving systemic chemotherapy, he died 3 months after the initial diagnosis. At autopsy, a diagnosis of multiple organ metastases from a malignant biphasic mesothelioma of the appendix was made. To our knowledge, this is only the second reported case of primary malignant mesothelioma of the appendix.}, } @article {pmid22552293, year = {2012}, author = {Jube, S and Rivera, ZS and Bianchi, ME and Powers, A and Wang, E and Pagano, I and Pass, HI and Gaudino, G and Carbone, M and Yang, H}, title = {Cancer cell secretion of the DAMP protein HMGB1 supports progression in malignant mesothelioma.}, journal = {Cancer research}, volume = {72}, number = {13}, pages = {3290-3301}, pmid = {22552293}, issn = {1538-7445}, support = {P01 CA114047/CA/NCI NIH HHS/United States ; P30 CA071789/CA/NCI NIH HHS/United States ; R01 CA160715/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Blotting, Western ; Disease Progression ; Enzyme-Linked Immunosorbent Assay ; HMGB1 Protein/*metabolism/physiology ; Humans ; Immunohistochemistry ; Mesothelioma/*metabolism/pathology ; Mice ; Transplantation, Heterologous ; Tumor Cells, Cultured ; }, abstract = {Human malignant mesothelioma is an aggressive and highly lethal cancer that is believed to be caused by chronic exposure to asbestos and erionite. Prognosis for this cancer is generally poor because of late-stage diagnosis and resistance to current conventional therapies. The damage-associated molecular pattern protein HMGB1 has been implicated previously in transformation of mesothelial cells. Here we show that HMGB1 establishes an autocrine circuit in malignant mesothelioma cells that influences their proliferation and survival. Malignant mesothelioma cells strongly expressed HMGB1 and secreted it at high levels in vitro. Accordingly, HMGB1 levels in malignant mesothelioma patient sera were higher than that found in healthy individuals. The motility, survival, and anchorage-independent growth of HMGB1-secreting malignant mesothelioma cells was inhibited in vitro by treatment with monoclonal antibodies directed against HMGB1 or against the receptor for advanced glycation end products, a putative HMGB1 receptor. HMGB1 inhibition in vivo reduced the growth of malignant mesothelioma xenografts in severe-combined immunodeficient mice and extended host survival. Taken together, our findings indicate that malignant mesothelioma cells rely on HMGB1, and they offer a preclinical proof-of-principle that antibody-mediated ablation of HMBG1 is sufficient to elicit therapeutic activity, suggesting a novel therapeutic approach for malignant mesothelioma treatment.}, } @article {pmid22550694, year = {2012}, author = {David, AM and Ogawa, H and Takahashi, K}, title = {A baseline profile of asbestos in the US-affiliated Pacific Islands.}, journal = {International journal of occupational and environmental health}, volume = {18}, number = {1}, pages = {22-28}, pmid = {22550694}, issn = {1077-3525}, support = {U54 CA143728/CA/NCI NIH HHS/United States ; }, mesh = {Asbestos/*poisoning ; Asbestosis/*diagnosis/*epidemiology ; Environmental Exposure/statistics & numerical data ; Humans ; Mesothelioma/*epidemiology ; Native Hawaiian or Other Pacific Islander ; Occupational Exposure/statistics & numerical data ; Pacific Islands/epidemiology ; United States ; }, abstract = {Asbestos is a recognized occupational and environmental hazard in the Asia-Pacific region, yet information regarding asbestos consumption, exposure, and asbestos-related diseases in the US-affiliated Pacific Islands (USAPIs) is scarce, and the situation regarding asbestos in these islands, particularly with regard to disease burden, surveillance, and health care capacity, is not well understood. Searching through scientific and "gray" literature and interviews with local cancer registry personnel and health professionals yielded no published data, only sufficient, indirect evidence of past and ongoing asbestos exposure, documented cases of mesothelioma and asbestosis, and minimal capacity for preventing and recognizing asbestos-related illnesses. Capacity and resource limitations within the USAPIs can impede regional progress in asbestos prevention and highlight the need for an integrated regional approach to address these data and capacity gaps. A regional mechanism to share expertise and resources and facilitate technical assistance to the USAPIs is urgently needed.}, } @article {pmid22545679, year = {2012}, author = {Marinaccio, A and Scarselli, A and Merler, E and Iavicoli, S}, title = {Mesothelioma incidence surveillance systems and claims for workers' compensation. Epidemiological evidence and prospects for an integrated framework.}, journal = {BMC public health}, volume = {12}, number = {}, pages = {314}, pmid = {22545679}, issn = {1471-2458}, mesh = {Adult ; Aged ; Female ; Humans ; Italy/epidemiology ; Logistic Models ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Occupational Diseases/*epidemiology ; Population Surveillance/*methods ; Workers' Compensation/*statistics & numerical data ; }, abstract = {BACKGROUND: Malignant mesothelioma is an aggressive and lethal tumour strongly associated with exposure to asbestos (mainly occupational). In Italy a large proportion of workers are protected from occupational diseases by public insurance and an epidemiological surveillance system for incident mesothelioma cases.

METHODS: We set up an individual linkage between the Italian national mesothelioma register (ReNaM) and the Italian workers' compensation authority (INAIL) archives. Logistic regression models were used to identify and test explanatory variables.

RESULTS: We extracted 3270 mesothelioma cases with occupational origins from the ReNaM, matching them with 1625 subjects in INAIL (49.7%); 91.2% (1,482) of the claims received compensation. The risk of not seeking compensation is significantly higher for women and the elderly. Claims have increased significantly in recent years and there is a clear geographical gradient (northern and more developed regions having higher claims rates). The highest rates of compensation claims were after work known to involve asbestos.

CONCLUSIONS: Our data illustrate the importance of documentation and dissemination of all asbestos exposure modalities. Strategies focused on structural and systematic interaction between epidemiological surveillance and insurance systems are needed.}, } @article {pmid22544626, year = {2012}, author = {Jung, SH and Kim, HR and Koh, SB and Yong, SJ and Chung, MJ and Lee, CH and Han, J and Eom, MS and Oh, SS}, title = {A decade of malignant mesothelioma surveillance in Korea.}, journal = {American journal of industrial medicine}, volume = {55}, number = {10}, pages = {869-875}, doi = {10.1002/ajim.22065}, pmid = {22544626}, issn = {1097-0274}, mesh = {Adolescent ; Adult ; Aged ; Asbestos/*toxicity ; Epidemiologic Studies ; Female ; Health Surveys ; Humans ; Incidence ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Diseases/*epidemiology/etiology ; Occupational Exposure/*adverse effects ; Population Surveillance/*methods ; Republic of Korea/epidemiology ; Risk Assessment/methods ; Time Factors ; Young Adult ; }, abstract = {BACKGROUND: The objectives of this study were to examine trends in mesothelioma incidence over a decade and to identify histories of asbestos exposure among cases in Korea.

METHODS: In 2001, The Korea Occupational Safety and Health Agency organized a nationwide cardiopulmonary pathology group and established a malignant mesothelioma surveillance system covering all general hospitals in Korea. Mesothelioma cases were reported to this surveillance system with information about age, gender, location, occupational history, asbestos exposure environment, date of diagnosis, diagnostic method, histopathologic subtype, occurrence site, and other clinical information. Additionally, an epidemiological survey was conducted using a structured verbal questionnaire to allow further evaluation of asbestos exposures.

RESULTS: A total of 399 cases of malignant mesothelioma were reported in the last decade, translating to approximately 40 annual cases, and an annual average incidence rate of 0.83 cases per million. Of the 152 patients interviewed by occupational physicians, 56 had occupational asbestos exposure histories (36.8%). Their occupations and industries included construction (19.7%), automobile repair (5.9%), asbestos textile, shipbuilding and repair, refinery work, boiler making, and asbestos cement work. Another 31 patients had environmental asbestos exposure histories.

CONCLUSIONS: Surveillance data indicate that malignant mesothelioma incidence in Korea is, thus far, lower than that of other developed countries, and that construction and environmental asbestos exposure were the main identifiable causes of malignant mesothelioma.}, } @article {pmid22544543, year = {2012}, author = {Finkelstein, MM}, title = {Malignant mesothelioma incidence among talc miners and millers in New York State.}, journal = {American journal of industrial medicine}, volume = {55}, number = {10}, pages = {863-868}, doi = {10.1002/ajim.22063}, pmid = {22544543}, issn = {1097-0274}, mesh = {Aged ; Aged, 80 and over ; Antiperspirants/toxicity ; Asbestos/*toxicity ; Asbestos, Amphibole/toxicity ; Dust ; Humans ; Incidence ; Male ; Mesothelioma/*epidemiology/etiology/pathology ; Middle Aged ; *Mining ; National Institute for Occupational Safety and Health, U.S. ; New York/epidemiology ; Occupational Diseases/*epidemiology/etiology/pathology ; Occupational Exposure/*adverse effects ; Registries ; Risk ; Risk Factors ; Talc/*toxicity ; United States ; }, abstract = {BACKGROUND: There is controversy about the potential for dust from the talc mines and mills of New York State to cause mesothelioma. Honda et al. published a study of mortality among New York talc workers and concluded that it was unlikely that the two deaths from mesothelioma were caused by talc ore dust. However, fibers of tremolite and anthophyllite have been found in the lungs of talc workers and Hull concluded that "New York talc exposure is associated with mesothelioma, and deserves further public health attention."

METHODS: Data concerning additional cases of mesothelioma in the cohort have been posted by NIOSH. I used information from the NIOSH website and the Honda report to analyze the incidence of mesothelioma during the years 1990-2007.

RESULTS: There were at least five new cases of mesothelioma in the cohort and mesothelioma incidence rates were at least five (1.6-11.7) times the rate in the general population (P < 0.01).

CONCLUSIONS: I conclude that: (1) mesothelioma has been diagnosed among members of the cohort at a rate in excess of that in the general population; (2) fibers of tremolite and anthophyllite have been detected in dust and the lungs of talc workers; and (3) these fibers are known causes of mesothelioma. It is prudent, on the balance of probabilities, to conclude that dusts from New York State talc ores are capable of causing mesothelioma in exposed individuals.}, } @article {pmid22544163, year = {2012}, author = {Dunning, KK and Adjei, S and Levin, L and Rohs, AM and Hilbert, T and Borton, E and Kapil, V and Rice, C and Lemasters, GK and Lockey, JE}, title = {Mesothelioma associated with commercial use of vermiculite containing Libby amphibole.}, journal = {Journal of occupational and environmental medicine}, volume = {54}, number = {11}, pages = {1359-1363}, doi = {10.1097/JOM.0b013e318250b5f5}, pmid = {22544163}, issn = {1536-5948}, support = {1R01TS000098-1/TS/ATSDR CDC HHS/United States ; ES10957/ES/NIEHS NIH HHS/United States ; U50/ATU573006S//PHS HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Aluminum Silicates/*adverse effects ; Cause of Death ; Cohort Studies ; Confidence Intervals ; *Extraction and Processing Industry ; Female ; Humans ; Inhalation Exposure/*adverse effects ; Lung Neoplasms/chemically induced/*mortality ; Male ; Mesothelioma/chemically induced/*mortality ; Middle Aged ; Occupational Exposure/*adverse effects ; Respiratory Tract Diseases/chemically induced/mortality ; Young Adult ; }, abstract = {OBJECTIVES: To describe asbestos-related mortality among manufacturing workers who expanded and processed Libby vermiculite that contained amphibole fiber.

METHODS: Standardized mortality ratio was calculated for 465 white male workers 31 years after last Libby vermiculite exposure.

RESULTS: Two workers died from mesothelioma, resulting in a significantly increased standardized mortality ratio of 10.5 (95% confidence interval, 1.3 to 38.0). These workers were in the upper 10th percentile of cumulative fiber exposure, that is, 43.80 and 47.23 fiber-years/cm, respectively. One additional worker with cumulative fiber exposure of 5.73 fiber-years/cm developed mesothelioma but is not deceased. There were no other significantly increased standardized mortality ratios.

CONCLUSIONS: Workers expanding and processing Libby vermiculite in a manufacturing setting demonstrated an increased risk for the development of mesothelioma following exposure to the amphibole fiber contained within this vermiculite ore source.}, } @article {pmid22542410, year = {2012}, author = {Carette, MF}, title = {[Follow-up of subjects occupationally exposed to asbestos: MRI and PET scans].}, journal = {Revue des maladies respiratoires}, volume = {29}, number = {4}, pages = {529-536}, doi = {10.1016/j.rmr.2011.09.052}, pmid = {22542410}, issn = {1776-2588}, mesh = {Asbestos/adverse effects ; Asbestosis/complications/*diagnostic imaging ; Disease Progression ; Follow-Up Studies ; Humans ; Limit of Detection ; Magnetic Resonance Imaging ; Mesothelioma/diagnostic imaging/etiology ; Monitoring, Physiologic/methods/standards ; *Occupational Exposure/adverse effects/analysis ; Pleural Diseases/diagnostic imaging/etiology ; Pleural Neoplasms/diagnostic imaging/etiology ; Positron-Emission Tomography ; Radiography ; }, abstract = {MRI and PET scans are not normally used for screening and follow-up of patients following occupational exposure to asbestos. These examinations usually complement the investigation of a parenchymal mass, an effusion or pleural thickening. PET and MRI have an excellent ability to define a parenchymal lesion as malignant (cancer versus rounded atelectasis) or a pleural lesion (mesothelioma versus plaque). MRI distinguishes perfectly the involvement of sub-pleural fat by bronchial carcinoma or mesothelioma. MRI, taking account of its lack of irradiation, could be regarded as suitable for potentially repeated examinations following initial screeing by CT scan. A comparative study of multidetector scanner versus MRI, including diffusion MRI could be, nevertheless, interesting. PET cannot be proposed for the follow up or for screening on account of the irradiation induced and the difficulty of access. Pleural plaques do not take up FDG. There is no specific study of asbestos related fibrosis and there is discordance between studies of other types of pulmonary fibrosis.}, } @article {pmid22537085, year = {2012}, author = {Takagi, A and Hirose, A and Futakuchi, M and Tsuda, H and Kanno, J}, title = {Dose-dependent mesothelioma induction by intraperitoneal administration of multi-wall carbon nanotubes in p53 heterozygous mice.}, journal = {Cancer science}, volume = {103}, number = {8}, pages = {1440-1444}, pmid = {22537085}, issn = {1349-7006}, mesh = {Animals ; Carcinogens/*administration & dosage ; Dose-Response Relationship, Drug ; Genes, p53 ; Heterozygote ; Injections, Intraperitoneal ; Male ; Mesothelioma/*chemically induced/epidemiology/pathology ; Mice ; Mice, Inbred Strains ; Nanotubes, Carbon/*adverse effects ; Peritoneum/*pathology ; Survival Analysis ; }, abstract = {Among various types of multi-wall carbon nanotubes (MWCNT) are those containing fibrous particles longer than 5 μm with an aspect ratio of more than three (i.e. dimensions similar to mesotheliomagenic asbestos). A previous study showed that micrometer-sized MWCNT (μm-MWCNT) administered intraperitoneally at a dose of 3000 μg/mouse corresponding to 1 × 10(9) fibers per mouse induced mesotheliomas in p53 heterozygous mice. Here, we report a dose-response study; three groups of p53 heterozygous mice (n = 20) were given a single intraperitoneal injection of 300 μg/mouse of μm-MWCNT (corresponding to 1 × 10(8) fibers), 30 μg/mouse (1 × 10(7)) or 3 μg/mouse (1 × 10(6)), respectively, and observed for up to 1 year. The cumulative incidence of mesotheliomas was 19/20, 17/20 and 5/20, respectively. The severity of peritoneal adhesion and granuloma formation were dose-dependent and minimal in the lowest dose group. However, the time of tumor onset was apparently independent of the dose. All mice in the lowest dose group that survived until the terminal kill had microscopic atypical mesothelial hyperplasia considered as a precursor lesion of mesothelioma. Right beneath was a mononuclear cell accumulation consisting of CD45- or CD3-positive lymphocytes and CD45/CD3-negative F4/80 faintly positive macrophages; some of the macrophages contained singular MWCNT in their cytoplasm. The lesions were devoid of epithelioid cell granuloma and fibrosis. These findings were in favor of the widely proposed mode of action of fiber carcinogenesis, that is, frustrated phagocytosis where the mesotheliomagenic microenvironment on the peritoneal surface is neither qualitatively altered by the density of the fibers per area nor by the formation of granulomas against agglomerates.}, } @article {pmid22536579, year = {2012}, author = {Labrèche, F and Case, BW and Ostiguy, G and Chalaoui, J and Camus, M and Siemiatycki, J}, title = {Pleural mesothelioma surveillance: validity of cases from a tumour registry.}, journal = {Canadian respiratory journal}, volume = {19}, number = {2}, pages = {103-107}, pmid = {22536579}, issn = {1916-7245}, mesh = {Aged ; Asbestos/adverse effects ; Female ; Humans ; Incidence ; Male ; Mesothelioma/chemically induced/*epidemiology ; Middle Aged ; Occupational Diseases/chemically induced/epidemiology ; Occupational Exposure/adverse effects ; Pleural Neoplasms/chemically induced/*epidemiology ; Quebec/epidemiology ; *Registries ; *Sentinel Surveillance ; }, abstract = {BACKGROUND: Pleural mesothelioma is a rare tumour associated with exposure to asbestos fibres. Fewer than than one-quarter of cases registered in the Quebec Tumour Registry (QTR) have been compensated as work-related. While establishing a surveillance system, this led to questioning as to whether there has been over-registration of cases that are not authentic pleural mesotheliomas in the QTR.

OBJECTIVE: To assess whether registered cases of pleural mesothelioma could be confirmed.

METHODS: A medical chart review was designed to assess the proportion of mesothelioma cases newly registered in the QTR in 2001⁄2002 that could be confirmed. For each registered case, clinical, medical imaging and pathology information were sought and, occasionally, additional immunohistochemistry staining was obtained. Three specialists - a chest physician, a radiologist and a pathologist - reviewed the available information and material, coding each mesothelioma case as to degree of certainty of the mesothelioma diagnosis.

RESULTS: The QTR reported 190 incident cases of mesothelioma (81% males) for the period. The specialists classified 81% of charts as 'certain⁄probable' or 'possible' mesotheliomas, 8% as 'unlikely to be a mesothelioma' and 11% as 'not a mesothelioma'. After excluding chart summaries of unsatisfactory quality, 87% to 88% of the charts were classified as 'certain⁄probable' or 'possible' mesotheliomas, and 9% to 11% were still considered 'not a mesothelioma'.

CONCLUSION: Tumour registry data are a valid source of information for mesothelioma surveillance. While there is some over-registration of mesothelioma cases in the QTR, a significant majority of registered cases appeared to be authentic. Over-registration cannot explain the greater proportion of cases that were not compensated.}, } @article {pmid22504106, year = {2012}, author = {Bahnassy, AA and Zekri, AR and Abou-Bakr, AA and El-Deftar, MM and El-Bastawisy, A and Sakr, MA and El-Sherif, GM and Gaafar, RM}, title = {Aberrant expression of cell cycle regulatory genes predicts overall and disease free survival in malignant pleural mesothelioma patients.}, journal = {Experimental and molecular pathology}, volume = {93}, number = {1}, pages = {154-161}, doi = {10.1016/j.yexmp.2012.04.001}, pmid = {22504106}, issn = {1096-0945}, mesh = {Adult ; Aged ; Cell Cycle/*genetics ; Cell Cycle Proteins/*genetics ; Disease-Free Survival ; Egypt ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Male ; Mesothelioma/genetics/*mortality/pathology ; Middle Aged ; Pleural Neoplasms/genetics/*mortality/pathology ; Young Adult ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a highly aggressive disease with a generally poor prognosis. Since escape from cell cycle checkpoint control is common in several solid tumors, the present study was performed to evaluate the role of some cell cycle regulatory genes in the development and progression of MPM.

PATIENTS AND METHODS: Aberrant expression of p14(ARF), p16(INK4A), p21(waf), p27(KIP), p53, mdm2 and Rb was assessed in 55 MPM cases from Egypt using immunohistochemistry and PCR techniques. Results were correlated with clinico-pathological prognostic factors, overall and disease free survival (OS&DFS).

RESULTS: Altered expression of p14(ARF), p16(INK4A), p21(waf), p27(KIP1), Rb, p53 and mdm2 proteins was detected in 50.9%, 54.5%, 53.3%, 61.8%, 53.3%, 58.2%, and 50.8% of cases, respectively. SV40 infection significantly correlated with p14(ARF), 16(INK4A), p27(kip1) and Rb aberrations (p=0.014, p=0.02, p=0.01, p=-0.01). Asbestos exposure significantly correlated with p53, p21(waf) and mdm2 aberrations (p=0.001, p=0.03, p=0.02). On multivariate analysis PS ≥ 2, p27(KIP1) and Rb aberrations were independent prognostic factors for OS (p=0.016, p=0.011, p=0.003) whereas on tumor recurrence, p27(KIP1) and Rb aberrations were independent prognostic factors for DFS (p=0.002, p=0.03, p=0.01).

CONCLUSIONS: MPM is a complex disease characterized by multiple genetic aberrations; some of them involve cell cycle regulatory genes. p14(ARF), p16(INK4A), Rb and p27(KIP1) seem to be involved in SV40-associated MPM whereas mdm2, p53 and p21(WAF) are related to asbestos exposure. In addition to recurrence and PS, only p27(KIP1)and Rb could be used as molecular prognostic markers in MPM.}, } @article {pmid22500091, year = {2012}, author = {Matsuzaki, H and Maeda, M and Lee, S and Nishimura, Y and Kumagai-Takei, N and Hayashi, H and Yamamoto, S and Hatayama, T and Kojima, Y and Tabata, R and Kishimoto, T and Hiratsuka, J and Otsuki, T}, title = {Asbestos-induced cellular and molecular alteration of immunocompetent cells and their relationship with chronic inflammation and carcinogenesis.}, journal = {Journal of biomedicine & biotechnology}, volume = {2012}, number = {}, pages = {492608}, pmid = {22500091}, issn = {1110-7251}, mesh = {Animals ; Asbestos/*poisoning/*toxicity ; Asbestosis/etiology/immunology ; Autoimmunity ; Cell Transformation, Neoplastic/chemically induced/*chemistry ; Chronic Disease ; Humans ; Inflammation/*etiology/immunology ; Mesothelioma/etiology/immunology ; }, abstract = {Asbestos causes lung fibrosis known as asbestosis as well as cancers such as malignant mesothelioma and lung cancer. Asbestos is a mineral silicate containing iron, magnesium, and calcium with a core of SiO(2). The immunological effect of silica, SiO(2), involves the dysregulation of autoimmunity because of the complications of autoimmune diseases found in silicosis. Asbestos can therefore cause alteration of immunocompetent cells to result in a decline of tumor immunity. Additionally, due to its physical characteristics, asbestos fibers remain in the lung, regional lymph nodes, and the pleural cavity, particularly at the opening sites of lymphatic vessels. Asbestos can induce chronic inflammation in these areas due to the production of reactive oxygen/nitrogen species. As a consequence, immunocompetent cells can have their cellular and molecular features altered by chronic and recurrent encounters with asbestos fibers, and there may be modification by the surrounding inflammation, all of which eventually lead to decreased tumor immunity. In this paper, the brief results of our investigation regarding reduction of tumor immunity of immunocompetent cells exposed to asbestos in vitro are discussed, as are our findings concerned with an investigation of chronic inflammation and analyses of peripheral blood samples derived from patients with pleural plaque and mesothelioma that have been exposed to asbestos.}, } @article {pmid22495008, year = {2012}, author = {van der Valk, FM and van Leeuwen, J}, title = {['Malignant peritoneal mesothelioma': a condition difficult to diagnose].}, journal = {Nederlands tijdschrift voor geneeskunde}, volume = {156}, number = {15}, pages = {A4269}, pmid = {22495008}, issn = {1876-8784}, mesh = {Antineoplastic Agents/therapeutic use ; Combined Modality Therapy ; Humans ; Hyperthermia, Induced ; Male ; Mesothelioma/*diagnosis/therapy ; Middle Aged ; Peritoneal Neoplasms/*diagnosis/therapy ; Prognosis ; }, abstract = {BACKGROUND: Malignant mesothelioma is an aggressive neoplasm, which arises from serous membranes, such as the pleura and the peritoneum. Malignant peritoneal mesothelioma is relatively rare, but the incidence is increasing worldwide because of intensive asbestos use during the 20th century.

CASE DESCRIPTION: A 60-year-old man complained of malaise, night sweating and weight loss and was seen by a specialist in internal medicine. Additional investigation included a CT scan, 2 PET-CT scans, 2 diagnostic laparoscopies and histological examination of peritoneum biopsies. After 7 months the diagnosis of malignant peritoneal mesothelioma was made.

CONCLUSION: Histological investigation is of great importance when there is indication of malignant peritoneal mesothelioma. There is not yet a consensus concerning the optimal treatment, but a small increase in survival can be achieved by systemic chemotherapy or intraperitoneal therapy consisting of hyperthermic intraperitoneal chemotherapy after cytoreductive surgery.}, } @article {pmid22486078, year = {2012}, author = {Carugno, M and Mensi, C and Sieno, C and Consonni, D and Riboldi, L}, title = {Asbestos exposure among hairdressers.}, journal = {La Medicina del lavoro}, volume = {103}, number = {1}, pages = {70-71}, pmid = {22486078}, issn = {0025-7818}, mesh = {Asbestos/*adverse effects ; *Beauty Culture ; Hair Preparations/*adverse effects ; Humans ; Italy/epidemiology ; Lung Neoplasms/epidemiology/*etiology ; Mesothelioma/epidemiology/*etiology ; Occupational Exposure/*adverse effects ; Risk Factors ; Surveys and Questionnaires ; }, } @article {pmid22475912, year = {2012}, author = {Aga, F and Yamamoto, Y and Norikane, T and Nishiyama, Y}, title = {A case of primary pericardial mesothelioma detected by 18F-FDG PET/CT.}, journal = {Clinical nuclear medicine}, volume = {37}, number = {5}, pages = {522-523}, doi = {10.1097/RLU.0b013e3182478c13}, pmid = {22475912}, issn = {1536-0229}, mesh = {Female ; *Fluorodeoxyglucose F18 ; Heart Neoplasms/*diagnostic imaging ; Humans ; Mesothelioma/*diagnostic imaging ; Middle Aged ; *Multimodal Imaging ; Pericardium/*diagnostic imaging ; *Positron-Emission Tomography ; *Tomography, X-Ray Computed ; }, abstract = {Primary pericardial mesothelioma is an extremely rare malignancy. We report a case of a 58-year-old woman who presented with fever and fatigue. She had no apparent history of occupational or incidental exposure to asbestos. A postcontrast-enhanced chest CT revealed a 77 × 56-mm mass lesion in the pericardium. The FDG PET/CT was carried out, which demonstrated an intense FDG uptake to a main pericardial tumor and disseminated lesions in the pericardium. Histologic examination confirmed the primary malignant pericardial mesothelioma.}, } @article {pmid22472194, year = {2012}, author = {Murphy, FA and Schinwald, A and Poland, CA and Donaldson, K}, title = {The mechanism of pleural inflammation by long carbon nanotubes: interaction of long fibres with macrophages stimulates them to amplify pro-inflammatory responses in mesothelial cells.}, journal = {Particle and fibre toxicology}, volume = {9}, number = {}, pages = {8}, pmid = {22472194}, issn = {1743-8977}, support = {G0901697/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Cell Line, Tumor ; Cell Survival/drug effects ; Culture Media, Conditioned ; Cytokines/*immunology/metabolism ; Dose-Response Relationship, Drug ; Humans ; Macrophage Activation/*drug effects/immunology ; Macrophages/*drug effects/immunology/pathology ; Mesothelioma/*immunology/pathology ; Microscopy, Electron, Scanning ; Nanotubes, Carbon/chemistry/*toxicity ; Particle Size ; Phagocytosis/drug effects/immunology ; Pleurisy/*etiology/immunology/pathology ; Time Factors ; }, abstract = {Carbon nanotubes (CNT) are high aspect ratio nanoparticles with diameters in the nanometre range but lengths extending up to hundreds of microns. The structural similarities between CNT and asbestos have raised concern that they may pose a similar inhalation hazard. Recently CNT have been shown to elicit a length-dependent, asbestos-like inflammatory response in the pleural cavity of mice, where long fibres caused inflammation but short fibres did not. However the cellular mechanisms governing this response have yet to be elucidated. This study examined the in vitro effects of a range of CNT for their ability to stimulate the release of the acute phase cytokines; IL-1β, TNFα, IL-6 and the chemokine, IL-8 from both Met5a mesothelial cells and THP-1 macrophages. Results showed that direct exposure to CNT resulted in significant cytokine release from the macrophages but not mesothelial cells. This pro-inflammatory response was length dependent but modest and was shown to be a result of frustrated phagocytosis. Furthermore the indirect actions of the CNT were examined by treating the mesothelial cells with conditioned media from CNT-treated macrophages. This resulted in a dramatic amplification of the cytokine release from the mesothelial cells, a response which could be attenuated by inhibition of phagocytosis during the initial macrophage CNT treatments. We therefore hypothesise that long fibres elicit an inflammatory response in the pleural cavity via frustrated phagocytosis in pleural macrophages. The activated macrophages then stimulate an amplified pro-inflammatory cytokine response from the adjacent pleural mesothelial cells. This mechanism for producing a pro-inflammatory environment in the pleural space exposed to long CNT has implications for the general understanding of fibre-related pleural disease and design of safe nanofibres.}, } @article {pmid23775153, year = {2012}, author = {G Benavides, F and Menéndez-Navarro, A and Delclòs, J and Luque, M}, title = {[Scientific evidence and legal liability in occupational health: indemnity claim based on lack of safety and hygiene controls after a worker's death due to mesothelioma].}, journal = {Archivos de prevencion de riesgos laborales}, volume = {15}, number = {2}, pages = {86-89}, doi = {10.12961/aprl.2012.15.2.04}, pmid = {23775153}, issn = {1138-9672}, mesh = {Aged ; Asbestos/adverse effects ; Cause of Death ; Humans ; *Liability, Legal ; Male ; *Mesothelioma/etiology ; *Occupational Diseases/etiology ; Occupational Exposure/*legislation & jurisprudence ; Occupational Health/*legislation & jurisprudence ; Spain ; }, abstract = {The aim of this paper is to reflect, under the precautionary principle, on the relationship between scientific causation and legal liability in connection with a lawsuit regarding compensation for lack of occupational safety and hygiene controls following the death of a worker with mesothelioma that had been previously accepted as an occupational disease. The worker had spent 28 years as a shipyard welder, with a diagnosis of occupationally-related mesothelioma in 2007, and who died in 2009. After reviewing the advances in a) scientific knowledge on the health effects of asbestos exposure, which were consolidated between 1955 and 1976, and b) the development of a regulatory framework for the protection of workers in Spain that began generically in 1940 and became more specific in 1982, we conclude that our case probably would have benefited from application of the precautionary principle, which is now widely accepted.}, } @article {pmid22460164, year = {2013}, author = {Tabata, C and Terada, T and Tabata, R and Yamada, S and Eguchi, R and Fujimori, Y and Nakano, T}, title = {Serum thioredoxin-1 as a diagnostic marker for malignant peritoneal mesothelioma.}, journal = {Journal of clinical gastroenterology}, volume = {47}, number = {1}, pages = {e7-11}, doi = {10.1097/MCG.0b013e31824e901b}, pmid = {22460164}, issn = {1539-2031}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*blood ; Early Detection of Cancer ; Female ; Humans ; In Vitro Techniques ; Male ; Mesothelioma/blood/*diagnosis ; Middle Aged ; Peritoneal Neoplasms/*blood/*diagnosis ; Predictive Value of Tests ; ROC Curve ; Sampling Studies ; Sensitivity and Specificity ; Thioredoxins/*blood ; }, abstract = {BACKGROUND: Diffuse malignant peritoneal mesothelioma (DMPM) is an aggressive malignant tumor of mesothelial origin that shows a limited response to cytoreductive surgery along with intraperitoneal chemotherapy. Therefore, diagnosing DMPM early is very important. Reactive oxygen species play an important role in asbestos toxicity, which is associated with the pathogenesis of DMPM growth. Thioredoxin-1 (TRX) is a small redox-active protein that demonstrates antioxidative activity associated with tumor growth. Here, we investigated the serum levels of TRX in patients with DMPM and compared them with those of a population that had been exposed to asbestos but did not have DMPM.

STUDY: The serum concentrations of TRX were measured in 15 DMPM patients and 34 individuals with benign asbestos-related diseases.

RESULTS: We demonstrated that the patients with DMPM had significantly higher serum levels of TRX than the population that had been exposed to asbestos but did not have DMPM.

CONCLUSIONS: Our data suggest that serum TRX concentration is a useful serum marker for DMPM.}, } @article {pmid22459593, year = {2012}, author = {Linton, A and Vardy, J and Clarke, S and van Zandwijk, N}, title = {The ticking time-bomb of asbestos: its insidious role in the development of malignant mesothelioma.}, journal = {Critical reviews in oncology/hematology}, volume = {84}, number = {2}, pages = {200-212}, doi = {10.1016/j.critrevonc.2012.03.001}, pmid = {22459593}, issn = {1879-0461}, mesh = {Animals ; Asbestos/*adverse effects ; Female ; Humans ; Male ; Mesothelioma/*etiology ; Occupational Exposure ; }, abstract = {The relationship between asbestos exposure and malignant mesothelioma (MM) has been well established. Despite bans on asbestos use in an increasing number of nations, the prolonged latency from exposure to diagnosis, and the ongoing presence and use of these dangerous fibres, have led to the increasing prevalence of this deadly disease worldwide. Whilst occupational contact has been implicated in the bulk of diagnosed cases over the past 50 years, a significant proportion of disease has been linked to para-occupational, domestic and environmental exposure. In this review, we will provide an update on the impact of historical and ongoing asbestos contact in both occupational and non-occupational settings. Furthermore, we will address the unresolved controversies surrounding the use of chrysotile asbestos, the effect of gender and genetics on development of this disease, childhood mesothelioma and co-aetiological factors including SV40 exposure.}, } @article {pmid22459200, year = {2013}, author = {Pasello, G and Ceresoli, GL and Favaretto, A}, title = {An overview of neoadjuvant chemotherapy in the multimodality treatment of malignant pleural mesothelioma.}, journal = {Cancer treatment reviews}, volume = {39}, number = {1}, pages = {10-17}, doi = {10.1016/j.ctrv.2012.03.001}, pmid = {22459200}, issn = {1532-1967}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*administration & dosage ; Chemotherapy, Adjuvant ; Clinical Trials as Topic ; Humans ; Mesothelioma/*drug therapy/radiotherapy/surgery ; Neoadjuvant Therapy ; Pleural Neoplasms/*drug therapy/radiotherapy/surgery ; }, abstract = {Malignant Pleural Mesothelioma (MPM) is an aggressive tumour with poor prognosis and increasing incidence in industrialized countries because of the previous widespread exposure to asbestos fibres and to the long lag period from time of exposure and the diagnosis of the disease. MPM shows high refractoriety to systemic treatment, single-modality treatment was generally ineffective and did not achieve higher results than supportive care. The incidence of local and distant recurrences after surgery remains high and that was the reason for many centres to perform combined treatments. In the attempt of reducing the incidence of local recurrences, a multimodality approach with surgery followed by adjuvant radiotherapy was explored. Extrapleural pneumonectomy (EPP) allows higher doses of radiotherapy to the whole hemithorax by avoiding pulmonary toxicity and the results of this approach is a significant reduction of loco-regional relapses; although, extrathoracic metastasis represent a major problem in the management of the disease because of the impact on overall survival. The success with surgical resection after neoadjuvant chemotherapy in stage IIIA lung cancer has been the impetus for several groups to apply this strategy in MPM aiming at reducing the incidence of distant relapse after surgery. Platinum-based chemotherapy plus gemcitabine or pemetrexed for 3-4 cycles followed by surgery and postoperative high-dose radiotherapy showed the best results in terms of overall and progression free survival. This review will focus on the main clinical studies and overview the results of different chemotherapy regimens in the neoadjuvant treatment of MPM.}, } @article {pmid22453207, year = {2012}, author = {Myojin, T and Azuma, K and Okumura, J and Uchiyama, I}, title = {Future trends of mesothelioma mortality in Japan based on a risk function.}, journal = {Industrial health}, volume = {50}, number = {3}, pages = {197-204}, doi = {10.2486/indhealth.ms1184}, pmid = {22453207}, issn = {1880-8026}, mesh = {Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Disease Progression ; Humans ; Japan/epidemiology ; Mesothelioma/epidemiology/*mortality ; Middle Aged ; Occupational Diseases/epidemiology/*mortality ; Occupational Exposure/*adverse effects ; Prognosis ; Risk Assessment/methods ; Time Factors ; }, abstract = {Mesothelioma is a malignancy with poor prognosis. It is chiefly caused by asbestos exposure and its symptoms can occur about 30-50 yr after the initial exposure. This study aims to predict the future trends in mesothelioma mortality in Japan using a method that is an alternative to the age-cohort model. Our approach is based on a risk function that links mesothelioma mortality combined with data pertaining to the population, size of the labor force, and quantity of asbestos imports. We projected the number of deaths occurring in individuals aged 50-89 for yr 2003-2050 using risk functions. Our results have indicated that mesothelioma mortality among Japanese people aged 50-89 yr will continue to increase until 2027 and reach a maximum of 66,327 deaths in the years 2003-2050. Our estimate has also suggested that the number of mesothelioma deaths could be significantly reduced if there were adequate compliance with the administrative level guidelines for occupational asbestos exposure.}, } @article {pmid22452101, year = {2011}, author = {Minoia, C and Sturchio, E and Porro, B and Ficociello, B and Zambelli, A and Imbriani, M}, title = {[microRNAs as biological indicators of environmental and occupational exposure to asbestos].}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {33}, number = {4}, pages = {420-434}, pmid = {22452101}, issn = {1592-7830}, mesh = {Asbestos/*adverse effects ; Environmental Exposure/*adverse effects ; GPI-Linked Proteins/genetics ; Genetic Markers/genetics ; Genetic Predisposition to Disease ; Humans ; Mesothelin ; Mesothelioma/etiology/*genetics ; MicroRNAs/*genetics ; Occupational Exposure/*adverse effects ; Osteopontin/genetics ; Peritoneal Neoplasms/etiology/*genetics ; Pleural Neoplasms/etiology/*genetics ; Prognosis ; }, abstract = {Malignant mesothelioma is an aggressive cancer refractory to current therapies, the incidence of which is expected to rise in the next decades. Exposure to asbestos is a well known risk factor, as InternationalAgency for Research and Cancer (IARC) classified this compound as group I (carcinogenic to humans). The lack of tumor biomarkers for diagnosis and medical survey plays a fundamental role for the development of a universally accepted therapeutic approach. In this review we evaluated the mechanism of asbestos carcinogenesis by analyzing activated oncogenes, genetic predisposition, and SV40 infection as cofactors. Therefore, interest has focused on microRNAs, 19-25 nucleotide-long single-stranded RNAs that negatively regulate gene expression by modulating translational efficiency of target genes involved in numerous cellular processes including development, differentiation, proliferation, apoptosis, and stress response. The analysis revealed a differential expression of miRNAs between mesothelioma and mesothelial cells, suggesting their potential role as oncogenes or tumor suppressor genes in mesothelioma oncogenesis. We have also investigated the role of polymorphism in the etiology and pathogenesis of mesothelioma, in order to evaluate the association between disease linked to asbestos exposure andgenetic variability. The identification of dysregulated miRNAs or frequent genetic polymorphisms as potential diagnostic biomarkers or as prognostic factors for malignant mesothelioma could facilitate the surveillance procedure of subjects exposed to asbestos.}, } @article {pmid22449815, year = {2012}, author = {Kurumatani, N}, title = {[A comprehensive review of literature to investigate development of global knowledge and consensus on asbestos carcinogenicity: up to the report and recommendations by UICC Working Group in 1964].}, journal = {Nihon eiseigaku zasshi. Japanese journal of hygiene}, volume = {67}, number = {1}, pages = {5-20}, doi = {10.1265/jjh.67.5}, pmid = {22449815}, issn = {0021-5082}, mesh = {Asbestos/*toxicity ; *Carcinogens ; Humans ; International Agencies ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; }, abstract = {This author comprehensively reviewed the literature on asbestos carcinogenicity up to the Report and Recommendations by Union Internationale Contra Cancrum (UICC) Working Group on asbestos and cancer in 1964. The first cases of mesothelioma and lung cancer in necropsied patients with asbestosis were reported in 1933 and 1934, respectively. After that, various studies examining the association between each of the diseases and asbestos exposure had been carried out until the meeting of the UICC Working Group: case report studies, case series studies, prevalence studies, historical cohort studies, and case-control studies. Newly reported studies including experimental studies in that meeting all supported the association. These findings on asbestos and cancer correspond well with Hill's criteria, which were just then advocated for evaluating causality epidemiologically. The Report and Recommendations by the Working Group concluded, "There is evidence of an association between exposure to asbestos and malignant neoplasia." and "The types of tumors ... are ... (1) carcinoma of the lungs, and (2) diffuse mesothelioma of the pleura and peritoneum." This author considers that the causal association between lung cancer or mesothelioma and asbestos was established at the meeting of UICC Working Group in 1964, not by the report on asbestos carcinogenicity in ILO (International Labour Organization) or IARC (International Agency for Research on Cancer) expert meetings in 1972, as the Japanese government announced. The amount of asbestos import in Japan doubled from 130,000 to 280,000 tons annually from 1964 to 1972. The government should have recognized the global knowledge on asbestos carcinogenicity in 1964; the amount of asbestos import could have been reduced greatly.}, } @article {pmid22444064, year = {2012}, author = {López-Abente, G and Fernández-Navarro, P and Boldo, E and Ramis, R and García-Pérez, J}, title = {Industrial pollution and pleural cancer mortality in Spain.}, journal = {The Science of the total environment}, volume = {424}, number = {}, pages = {57-62}, doi = {10.1016/j.scitotenv.2012.02.047}, pmid = {22444064}, issn = {1879-1026}, mesh = {Air Pollutants/analysis/*toxicity ; Air Pollution/*adverse effects/analysis ; Asbestos/toxicity ; Bayes Theorem ; *Environmental Exposure ; Environmental Monitoring ; Epidemiological Monitoring ; Female ; Humans ; Male ; Mesothelioma/chemically induced/epidemiology/mortality ; Occupational Exposure ; Pleural Neoplasms/*chemically induced/epidemiology/*mortality ; Poisson Distribution ; Risk ; Risk Factors ; Spain/epidemiology ; }, abstract = {Pleural cancer mortality is an acknowledged indicator of exposure to asbestos and mesothelioma mortality but in 15%-20% of cases no exposure can be recalled. In the past, asbestos was used in many industries and it is still found in many installations. Our objective was to ascertain whether there might be excess pleural cancer mortality among populations residing in the vicinity of Spanish industrial installations that are governed by the Integrated Pollution Prevention and Control (IPPC) Directive and the European Pollutant Release and Transfer Register Regulation and report their emissions to air. An ecological study was designed to examine pleural cancer mortality at a municipal level (8098 Spanish towns) over the period 1997-2006, during which 2146 deaths were registered. We conducted an exploratory "near vs. far" analysis to estimate the relative risks (RRs) of towns situated at a distance of <2 km from installations. This analysis was repeated for each of the 24 industrial groups. RR and their 95% credible intervals (95% CIs) were estimated on the basis of a Poisson conditional autoregressive Bayesian model with explanatory variables. Integrated nested Laplace approximations were used as a Bayesian inference tool. Analysis showed statistically significant RRs in both sexes in the vicinity of 7 of the 24 industrial groups studied (RR, 95% CI), namely, biocide facilities (2.595, 1.459-4.621), ship-building (2.321, 1.379-3.918), glass and mineral fibre production (1.667, 1.041-2.665), non-hazardous waste treatment (1.737, 1.077-2.799), galvanising (1.637, 1.139-2.347), organic chemical plants (1.386, 1.075-1.782) and the food and beverage sector (1.255, 1.006-1.562). In the proximity of sources pertaining to the biocide, organic chemical and galvanising sectors, the risk was seen to be rising among men and women, a finding that could indicate airborne environmental exposure. These results support that residing in the vicinity of IPPC-registered industries that release pollutants to the air constitutes a risk factor for pleural cancer.}, } @article {pmid22440140, year = {2013}, author = {Diego, C and Velasco-García, MI and Cruz, MJ and Untoria, MD and Morell, F and Ferrer, J}, title = {[Asbestos pulmonary content in workers of Ferrol shipyards, Spain].}, journal = {Medicina clinica}, volume = {140}, number = {4}, pages = {152-156}, doi = {10.1016/j.medcli.2012.01.023}, pmid = {22440140}, issn = {1578-8989}, mesh = {Aged ; Aged, 80 and over ; Asbestos/*analysis ; Humans ; Lung/*chemistry ; Male ; Middle Aged ; Occupational Exposure/*analysis ; Ships ; Spain ; }, abstract = {BACKGROUND AND OBJECTIVE: In the last years, a study is being conducted about exposure to asbestos among shipyards workers in order to know the diagnosis of the diseases associated with the exposure. Our goal was to know the asbestos pulmonary contents in this population.

MATERIAL AND METHODS: We obtained autopsy pulmonary samples from individuals who had worked in Ferrol shipyards. We analyzed samples from both lungs in most cases. After removing the lung organic matter with sodium hypochlorite, the inorganic residue was analyzed with optic microscopy. Results were expressed as asbestos bodies (AB) per gram of dry tissue. We considered as disease causative levels those above 1,000 AB/g.

RESULTS: We studied 30 males, with a mean age of 67 years (r: 56-89 years). Twenty-six were smokers or former smokers, and 4 had never smoked. All had a lung, pleural or peritoneal disease related to asbestos exposure (16 lung cancer, 6 mesothelioma, 25 benign pleural disease). Only in 6 out of the 16 lung cancer cases there was coexisting asbestosis. The median (interval) of AB was 6,171 (249-4,660,059) AB/g. Ninety-seven per cent of individuals had levels above 1,000 AB/g. There was a correlation between AB and age (r=.5676; P=.0011).

CONCLUSIONS: Workers from Ferrol shipyards who were analyzed had increased pulmonary levels of asbestos. It is essential to raise clinical suspicion of asbestos as a factor that can potentially cause lung disease in this group.}, } @article {pmid22439416, year = {2012}, author = {Dellaportas, D and Kairi-Vassilatou, E and Lykoudis, P and Mavrigiannaki, P and Mellou, S and Kleanthis, CK and Kondi-Pafiti, A}, title = {Peritoneal mesotheliomas mimicking adnexal tumors. Clinicopathological characteristics of four cases and a short literature review.}, journal = {European journal of gynaecological oncology}, volume = {33}, number = {1}, pages = {101-104}, pmid = {22439416}, issn = {0392-2936}, mesh = {Adnexal Diseases/*diagnosis ; Adult ; Cysts/*diagnosis ; Diagnosis, Differential ; Female ; Humans ; Mesothelioma/*diagnosis/pathology/surgery ; Middle Aged ; Peritoneal Neoplasms/*diagnosis/pathology/surgery ; }, abstract = {Three cases of peritoneal benign cystic mesotheliomas in women 32-34 years of age and one case of peritoneal malignant mesothelioma in a 47-year-old woman are reported. All cases presented with abdominal discomfort and/or pain and the physical and radiological diagnostic methods showed adnexal tumors. The cystic mesotheliomas developed in the cul-de-sac and the right pelvic sidewall, presented as multiple small cysts or large multilocular cystic mass. The malignant mesothelioma showed extensive infiltration of the omentum the intestinal loops and the surface of the uterus and adnexa, with bilateral hydrosalpinx and ascites. All cases presented histological and immunohistochemical characteristics consistent with tumors of mesothelial origin. No history of asbestos exposure was reported. The correct diagnostic and therapeutic approaches to these neoplasms are discussed.}, } @article {pmid22438785, year = {2012}, author = {Mott, FE}, title = {Mesothelioma: a review.}, journal = {Ochsner journal}, volume = {12}, number = {1}, pages = {70-79}, pmid = {22438785}, issn = {2831-4107}, abstract = {Mesothelioma is an insidious disease with long latency after asbestos exposure. New cases are continually diagnosed, although levels are declining with recognition of the asbestos risk and efforts to remove asbestos from the workplace. Treatment for early stage disease with surgery and radiation is potentially curative, but many patients either are too ill to undergo aggressive surgery or present with advanced disease. Chemotherapy with cisplatin and pemetrexed is considered standard, although relapse is common. Second-line therapy is disappointing. New targeted therapies may pose promise and are being addressed in various clinical trial settings. Palliative care remains an important component of the management of this devastating illness.}, } @article {pmid22424699, year = {2012}, author = {Santos, C and Gamboa, F and Fradinho, F and Pêgo, A and Carvalho, L and Bernardo, J}, title = {Deciduoid pleural mesothelioma--a rare entity in a young woman.}, journal = {Revista portuguesa de pneumologia}, volume = {18}, number = {6}, pages = {294-298}, doi = {10.1016/j.rppneu.2012.02.004}, pmid = {22424699}, issn = {2172-6825}, mesh = {Adult ; Female ; Humans ; *Mesothelioma/diagnosis/therapy ; *Pleural Neoplasms/diagnosis/therapy ; }, abstract = {Deciduoid Mesothelioma is a rare variant of epithelioid mesothelioma; it was initially thought that it only occurred in the peritoneum of young women and had nothing to do with asbestos exposure. However, since these early findings it has also been observed in the pleura and the pericardium, with possible association to asbestos. In general the prognosis is poor compared to epithelioid mesothelioma. 45 cases have been reported in the literature up to now, 22 of these were located in the pleural cavity. The authors describe a case of deciduoid pleural mesothelioma in a 40-year-old-woman who presented with right pleuritic chest pain, with no history of asbestos exposure, treated with chemotherapy followed by surgery and who died postoperatively.}, } @article {pmid22411970, year = {2012}, author = {Li, P and Deng, SS and Wang, JB and Iwata, A and Qiao, YL and Dai, XB and Boffetta, P}, title = {Occupational and environmental cancer incidence and mortality in China.}, journal = {Occupational medicine (Oxford, England)}, volume = {62}, number = {4}, pages = {281-287}, doi = {10.1093/occmed/kqs016}, pmid = {22411970}, issn = {1471-8405}, mesh = {China/epidemiology ; Environmental Exposure/*adverse effects ; Evidence-Based Medicine ; Female ; Humans ; Incidence ; Male ; Neoplasms/*epidemiology/etiology ; Occupational Diseases/*epidemiology ; Occupational Exposure/*adverse effects ; Registries ; Risk Factors ; }, abstract = {BACKGROUND: Most cancers are due to environmental, occupational or other non-genetic factors and are potentially preventable.

AIMS: To provide an evidence-based assessment of the burden of occupational and environmental-related cancers in China in 2005.

METHODS: The population attributable fraction (PAF) was calculated based on the assumption of no occupational agent exposure. Relative risk estimates for specific cancers of interest and prevalence of exposure were mainly derived from large-scale studies. Data on cancer incidence and mortality was obtained from the Third National Death Cause Survey and cancer registries in China.

RESULTS: We estimated that a total of 48,511 deaths of cancer were attributable to occupational agents in China in 2005, with 34,975 among men (3.1% of all cancer deaths) and 13,536 among women (2.1%). A total of 59,410 incident cases of cancer were attributable to occupational agents in China in 2005, with 42,724 among men (2.8% of all cancer incident cases) and 16,686 among women (1.6%). The highest PAF was observed for mesothelioma with asbestos, followed by leukaemia, bladder and lung cancers. Indoor radon was responsible for 0.2% of lung cancer-related deaths among men and women.

CONCLUSIONS: Occupational agents represent an important cause of cancer, but indoor radon plays a relatively limited role in cancer causes in China. Our report provides strong evidence of the need for policy makers to develop strategies to reduce the risk of occupational cancers.}, } @article {pmid22406029, year = {2012}, author = {Siesling, S and van der Zwan, JM and Izarzugaza, I and Jaal, J and Treasure, T and Foschi, R and Ricardi, U and Groen, H and Tavilla, A and Ardanaz, E and , }, title = {Rare thoracic cancers, including peritoneum mesothelioma.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {48}, number = {7}, pages = {949-960}, doi = {10.1016/j.ejca.2012.02.047}, pmid = {22406029}, issn = {1879-0852}, support = {11700/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Europe/epidemiology ; Female ; Humans ; Incidence ; Infant ; Infant, Newborn ; Male ; Mesothelioma/*epidemiology/mortality ; Middle Aged ; Neoplasms, Glandular and Epithelial/epidemiology ; Peritoneal Neoplasms/epidemiology ; Population Surveillance ; Prevalence ; Rare Diseases/epidemiology ; Thymus Neoplasms/*epidemiology/mortality ; Tracheal Neoplasms/*epidemiology/mortality ; }, abstract = {Rare thoracic cancers include those of the trachea, thymus and mesothelioma (including peritoneum mesothelioma). The aim of this study was to describe the incidence, prevalence and survival of rare thoracic tumours using a large database, which includes cancer patients diagnosed from 1978 to 2002, registered in 89 population-based cancer registries (CRs) and followed-up to 31st December 2003. Over 17,688 cases of rare thoracic cancers were selected based on the list of the RACECARE project. Mesothelioma was the most common tumour (19 per million per year) followed by epithelial tumours of the trachea and thymus (1.3 and 1.7, respectively). The age standardised incidence rates of epithelial tumours of the trachea was double in Eastern and Southern Europe versus the other European regions: 2 per million per year. Epithelial tumours of the thymus had the lowest incidence in Northern and Eastern Europe and UK and Ireland(1) and somewhat higher incidence in Central and Southern Europe.(2) Highest incidence in mesothelioma was seen in UK and Ireland(23) and lowest in Eastern Europe.(4) Patients with tumours of the thymus had the best prognosis (1-year survival 85%, 66% at 5 years). Five year survival was lowest for the mesothelioma 5% compared to 14% of patients with tumours of the trachea. Mesothelioma was the most prevalent rare cancer (12,000 cases), followed by thymus (7000) and trachea (1400). Cancer Registry (CR) data play an important role in revealing the burden of rare thoracic cancers and monitoring the effect of regulations on asbestos use and smoking related policies.}, } @article {pmid22405114, year = {2012}, author = {Letourneux, M and Clin, B and Marquignon, MF and Gauberti, P}, title = {[What tools should be used for follow-up post occupational exposure? What should be the frequency?].}, journal = {Revue des maladies respiratoires}, volume = {29}, number = {2}, pages = {205-212}, doi = {10.1016/j.rmr.2011.07.008}, pmid = {22405114}, issn = {1776-2588}, mesh = {Asbestos/*adverse effects ; Asbestosis/*diagnosis ; Continuity of Patient Care ; Humans ; Lung Neoplasms/chemically induced/*diagnosis ; Mesothelioma/chemically induced/*diagnosis ; Occupational Exposure/*adverse effects ; Radiography, Thoracic ; }, abstract = {As long as the value of screening for cancers related to asbestos is not proven in the population at risk, the medical benefits of follow-up post-professional exposure remain uncertain and the only justification is to answer the questions of anxious retired workers concerning the consequences of their past-exposure and to provide compensation for any abnormalities that are demonstrated. In this country, to answer the questions posed in the title of this contribution in the case of pathologies related to asbestos, it is necessary, after verifying the fact and the level of exposure, to identify the pleural or pulmonary fibrosis and, above all, the pleural plaques, which constitute the essential lesions currently screened for. Thoracic CT scanning without contrast is the examination of choice to achieve this objective. There are, however, two significant problems. On one hand there is a high incidence of pulmonary micronodules, the necessary surveillance of which requires subsequent scans, leading to increased irradiation and anxiety. On the other hand the diagnostic uncertainty concerning discrete lesions is a source of confusion for the persons followed-up. There are, at present, neither scientific criteria to determine the optimum frequency of examination nor any arguments for replacing the pragmatic proposals of the consensus conference of 1999. It is important, therefore, to provide a medical assessment appropriate to the symptoms and anxiety expressed by a person previously exposed to asbestos. Overall it is necessary to question the benefit to the exposed person, in terms of quality of life, of a regular search for lesions that would usually be asymptomatic if not identified. Would it not be more judicious and more equitable to compensate persons whose past-exposure is sufficient to increase significantly their risk of cancer independently of the presence of benign abnormalities.}, } @article {pmid22399624, year = {2012}, author = {Neri, M and Ugolini, D and Boccia, S and Canessa, PA and Cesario, A and Leoncini, G and Mutti, L and Bonassi, S}, title = {Chemoprevention of asbestos-linked cancers: a systematic review.}, journal = {Anticancer research}, volume = {32}, number = {3}, pages = {1005-1013}, pmid = {22399624}, issn = {1791-7530}, mesh = {Asbestos/*toxicity ; Carcinogens/*toxicity ; *Chemoprevention ; Humans ; Neoplasms/chemically induced/*prevention & control ; }, abstract = {Asbestos has been used extensively and, in spite of many countries having banned most of its uses, professional, domestic and environmental exposure has not ceased worldwide. Inhaled asbestos fibers can lead to malignant mesothelioma, lung cancer and non-cancerous conditions, while the substance persists indefinitely in the lung and pleural tissue, resulting in continuous damage. Exposed individuals may be offered medical surveillance or compensation, but nothing is currently being done to lower their specific cancer risk: chemoprevention seems a promising approach. A web search and a PubMed review of the literature on chemoprevention trials in individuals exposed to asbestos have been conducted. Forty-six articles on five projects were found and newly reviewed but, surprisingly, no novel trials have been set up for twenty years, although considerable advances have been gained in cancer chemoprevention. A re-consideration of possibilities offered by chemoprevention should be encouraged. New trials based on the most recently characterized molecules should be planned, taking into account specific issues such as the need for a very large number of participants and a long follow up or, alternatively, the use of biomarkers as surrogate endpoints. The long latency of asbestos related diseases may offer delayed intervention opportunities. The lack of chemoprevention trials for asbestos exposure highlights the urgent need for research in this field.}, } @article {pmid22388762, year = {2012}, author = {Ordóñez, NG}, title = {Pleomorphic mesothelioma: report of 10 cases.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {25}, number = {7}, pages = {1011-1022}, doi = {10.1038/modpathol.2012.39}, pmid = {22388762}, issn = {1530-0285}, mesh = {Aged ; Biomarkers, Tumor/analysis ; Humans ; Immunohistochemistry ; Male ; Mesothelioma/metabolism/*ultrastructure ; Microscopy, Electron, Transmission ; Middle Aged ; Peritoneal Neoplasms/metabolism/*ultrastructure ; Pleural Neoplasms/metabolism/*ultrastructure ; }, abstract = {Mesotheliomas with pleomorphic features are rare and only a few studies on this mesothelioma variant have been published. Little information regarding the immunoprofile of these tumors and none on their electron microscopic features was included in these studies. Herein are reported 10 cases of pleomorphic mesothelioma that were investigated using a large panel of immunohistochemical markers, 4 of which were also studied by electron microscopy. All of the patients were men and seven had a history of asbestos exposure. Nine of the cases originated in the pleura and one in the peritoneum. Histologically, the tumors were characterized by being composed of large, often discohesive, cells that varied in size and shape, had dense abundant eosinophilic cytoplasm, and single or multiple irregular nuclei, which often contained one or several large nucleoli. Mitotic activity was high and atypical mitoses frequent. Immunoreactivity for pan-keratin and keratin 7 was strong in all of the cases. Expression for calretinin, WT1, podoplanin, mesothelin and keratin 5/6 was also frequent, but variable. All cases were negative for MOC-31, carcinoembryonic antigen, CD15, TAG-72 and thyroid transcription factor-1. Electron microscopy often showed the presence of abundant long, slender microvilli on the cell membrane of the neoplastic cells. These findings demonstrate that, contrary to what has been suggested by some investigators, both immunohistochemistry and electron microscopy can be very helpful in assisting in the diagnosis of pleomorphic mesotheliomas. That the seven patients who underwent extrapleural pneumonectomy had extensive lymph node metastasis and that the median survival of those patients for whom follow-up information was available was only 8.2 months indicates that mesotheliomas with pleomorphic features are associated with highly aggressive clinical behavior. Therefore, when this subtype of epithelioid mesothelioma is present, it should be reported as it can significantly affect the prognosis and treatment of the patient.}, } @article {pmid22382838, year = {2012}, author = {Yamashita, K and Yoshioka, Y}, title = {[Safety assessment of nanomaterials in reproductive developmental field].}, journal = {Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan}, volume = {132}, number = {3}, pages = {331-335}, doi = {10.1248/yakushi.132.331}, pmid = {22382838}, issn = {1347-5231}, mesh = {Animals ; Female ; Fetus/*drug effects ; Humans ; Mice ; Nanoparticles/toxicity ; Nanostructures/*toxicity ; Nanotubes, Carbon/toxicity ; Particle Size ; Pregnancy/*drug effects ; Reproduction/*drug effects ; Safety ; Silicon Dioxide/pharmacokinetics/*toxicity ; }, abstract = {A diverse array of nanomaterials (NMs) such as amorphous nanosilica and carbon nanotubes have become widespread in use due to the development of nanotechnology. NMs are already being applied in universal fields because they have unique physicochemical properties. On the other hand, the increasing use of NMs has raised public concern about their potential risks to human health. In particular, recent reports indicated that carbon nanotubes induced mesothelioma-like lesions in mice, in a way similar to those induced by crocidolite asbestos. However, current knowledge of the potential risk of nanomaterials is considered insufficient. Because NMs have the potential to improve the quality of human life, it is essential to ensure the safety of NMs and provide information for designing NMs with safety. Especially, few studies have examined the effect of NMs on maintenance of pregnancy. Similar to the cases of thalidomide, a lot of evidence shows that fetuses are affected more than adults by a variety of environmental toxins because of physiological immaturity. Therefore it is essential to examine the effect of NMs on fetuses and pregnancies. Here we introduce the potential risk of amorphous nanosilica, most widely used NMs in food and the cosmetics field, to induce fetotoxicity and useful information for developing NMs with safety.}, } @article {pmid22374657, year = {2012}, author = {Ploenes, T and Osei-Agyemang, T and Nestle, U and Waller, CF and Passlick, B}, title = {[Malignant pleural mesothelioma].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {137}, number = {10}, pages = {481-486}, doi = {10.1055/s-0031-1298905}, pmid = {22374657}, issn = {1439-4413}, mesh = {Asbestos/*poisoning ; Humans ; Mesothelioma/*diagnosis/etiology/*therapy ; Pleural Neoplasms/*diagnosis/etiology/*therapy ; }, abstract = {Malignant pleural mesothelioma (MMP) is a highly aggressive tumor arising of the pleural mesothelium. Asbestos exposure is the main factor involved in the pathogenesis of MMP and according to the late ban of this agent in 2005 the peak incidence in Europe is expected in the next twenty years. The highly aggressive behaviour of this tumor results in a poor prognosis with a mean overall survival between 7 and 9 months. Despite the progress made in diagnosis and therapy of this entity the optimal treatment remains a subject of debate. In this article we review the current state of treatment and diagnosis.}, } @article {pmid22372902, year = {2012}, author = {Jasani, B and Gibbs, A}, title = {Mesothelioma not associated with asbestos exposure.}, journal = {Archives of pathology & laboratory medicine}, volume = {136}, number = {3}, pages = {262-267}, doi = {10.5858/arpa.2011-0039-RA}, pmid = {22372902}, issn = {1543-2165}, mesh = {Asbestos/*poisoning ; Cocarcinogenesis ; Environmental Exposure/*adverse effects ; Humans ; Mesothelioma/*etiology ; Pleural Neoplasms/*etiology ; Polyomavirus Infections/complications/virology ; Simian virus 40/physiology ; Tumor Virus Infections/complications/virology ; Zeolites/poisoning ; }, abstract = {CONTEXT: Despite asbestos being identified as the single most important cause of malignant mesothelioma, the tumor is known to occur in only 10% to 20% of heavily exposed individuals. In addition, about 20% of the patients have no history of asbestos exposure even after detailed assessment. Therefore, there has been speculation for some time that asbestos alone may not be sufficient to cause mesothelioma and that other factors may be involved either as cocarcinogens or as independent mechanisms of cancer causation.

OBJECTIVE: To give a brief review of nonasbestos fiber erionite and therapeutic radiation as 2 established examples of asbestos-independent mechanisms, of the potential emerging role of man-made fibers such as carbon nanotubes, and of polyoma virus SV40 (simian virus 40) as a potential example of the cocarcinogenic mode of involvement.

DATA SOURCES: Relevant recent literature has been surveyed to portray and provide the evidence in favor of the examples.

CONCLUSIONS: Erionite has emerged as the most important example of nonasbestos-mediated cause of mesothelioma in regions such as Turkey where exposure to this type of fiber is highly prevalent. Recently, the polyoma virus SV40 has been unexpectedly discovered as an effective cocarcinogen of asbestos in the causation of animal mesothelioma, though despite considerable research, its potential role in human mesothelioma remains unproven.}, } @article {pmid22369943, year = {2012}, author = {Yamazaki, H and Naito, M and Ghani, FI and Dang, NH and Iwata, S and Morimoto, C}, title = {Characterization of cancer stem cell properties of CD24 and CD26-positive human malignant mesothelioma cells.}, journal = {Biochemical and biophysical research communications}, volume = {419}, number = {3}, pages = {529-536}, doi = {10.1016/j.bbrc.2012.02.054}, pmid = {22369943}, issn = {1090-2104}, mesh = {Antineoplastic Agents, Phytogenic/pharmacology ; Biomarkers, Tumor/analysis/genetics/*metabolism ; CD24 Antigen/analysis/genetics/*metabolism ; Cell Division/genetics ; Cell Line, Tumor ; Daunorubicin/pharmacology ; Dipeptidyl Peptidase 4/analysis/genetics/*metabolism ; Drug Resistance, Neoplasm/genetics ; ErbB Receptors/metabolism ; Etoposide/pharmacology ; Gene Expression ; Gene Knockdown Techniques ; Humans ; Insulin-Like Growth Factor Binding Protein 3/metabolism ; Insulin-Like Growth Factor Binding Proteins/metabolism ; Mesothelioma/genetics/metabolism/*pathology ; Neoplasm Invasiveness ; Neoplastic Stem Cells/drug effects/metabolism/*pathology ; RNA Interference ; RNA, Small Interfering/genetics ; }, abstract = {Malignant mesothelioma (MM) is an asbestos-related malignancy characterized by rapid growth and poor prognosis. In our previous study, we have demonstrated that several cancer stem cell (CSC) markers correlated with CSC properties in MM cells. Among these markers, we focused on two: CD24, the common CSC marker, and CD26, the additional CSC marker. We further analyzed the CSC properties of CD24 and CD26-positve MM cells. We established RNAi-knockdown cells and found that these markers were significantly correlated with chemoresistance, proliferation, and invasion potentials in vitro. Interestingly, while Meso-1 cells expressed both CD24 and CD26, the presence of each of these two markers was correlated with different CSC property. In addition, downstream signaling of these markers was explored by microarray analysis, which revealed that their expressions were correlated with several cancer-related genes. Furthermore, phosphorylation of ERK by EGF stimulation was significantly affected by the expression of CD26, but not CD24. These results suggest that CD24 and CD26 differentially regulate the CSC potentials of MM and could be promising targets for CSC-oriented therapy.}, } @article {pmid22352060, year = {2011}, author = {Kodama, M and Tateno, H and Tasak, S and Soejima, K and Asano, K and Hayashi, Y}, title = {[An autopsied case of primary malignant pericardial mesothelioma diagnosed antemortally].}, journal = {Nihon Kokyuki Gakkai zasshi = the journal of the Japanese Respiratory Society}, volume = {49}, number = {12}, pages = {964-969}, pmid = {22352060}, issn = {1343-3490}, mesh = {Adult ; Autopsy ; Cardiac Tamponade/*pathology ; Humans ; Male ; Mesothelioma/*pathology ; }, abstract = {A 40-year-old man was admitted to our hospital with a 1-month history of dyspnea and appetite loss. Chest computed tomography and echocardiography showed moderate pericardial effusion and pericardial thickening. The patient had no history of exposure to asbestos. We created a pericardial window in order to make a diagnosis and to relieve the symptoms using video-assisted thoracoscopic surgery and performed biopsies of the pericardium and the pleura. Immunohistologic analysis of the pericardium confirmed a diagnosis of biphasic pericardial mesothelioma. We gave the patient two cycles of chemotherapy, including pemetrexed and platinum, but his condition did not improve and he died 3 months after onset.}, } @article {pmid22351650, year = {2013}, author = {Kalogeraki, AM and Tamiolakis, DJ and Lagoudaki, ED and Papadakis, MN and Papadakis, GZ and Agelaki, SI and Stathopoulos, EN and Tzardi, MN}, title = {Familial mesothelioma in first degree relatives.}, journal = {Diagnostic cytopathology}, volume = {41}, number = {7}, pages = {654-657}, doi = {10.1002/dc.21859}, pmid = {22351650}, issn = {1097-0339}, mesh = {Adult ; Asbestos/*adverse effects ; Biomarkers, Tumor/metabolism ; Family ; *Family Health ; Female ; Genetic Predisposition to Disease ; Humans ; Male ; Mesothelioma/chemically induced/genetics/metabolism/*pathology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/chemically induced/genetics/metabolism/*pathology ; Smoking ; }, abstract = {Occupational asbestos exposure is believed to be the primary etiologic link to mesothelioma. However, in the evaluation of familial mesothelioma, it is important to consider the possibility of household exposure to asbestos. In this study, we report a family in which the father with prolonged occupational asbestos exposure developed malignant pleural mesothelioma and his daughter 14 years later mesothelioma in situ with focally early invasion. Several reports of familial aggregations of mesothelioma strongly support that genetic factors in collaboration with environmental exposure may contribute etiologically to an as yet unknown fraction of occurrence of this disease.}, } @article {pmid22345416, year = {2012}, author = {Chen, SE and Pace, MB}, title = {Malignant pleural mesothelioma.}, journal = {American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists}, volume = {69}, number = {5}, pages = {377-385}, doi = {10.2146/ajhp110281}, pmid = {22345416}, issn = {1535-2900}, mesh = {Antineoplastic Agents/*therapeutic use ; Chemotherapy, Adjuvant/methods ; Clinical Trials as Topic ; Combined Modality Therapy ; Humans ; Mesothelioma/etiology/pathology/*therapy ; Neoplasm Staging ; Pleural Neoplasms/etiology/pathology/*therapy ; Prognosis ; Survival Rate ; Treatment Outcome ; }, abstract = {UNLABELLED: PURPOSE The etiology, diagnosis, staging, and management of malignant pleural mesothelioma (MPM) are reviewed, with an emphasis on clinical trials of newer approaches to first-line, second-line, and adjuvant chemotherapy.

SUMMARY: In the past decade, more effective chemotherapy regimens have been developed for patients with MPM, a rapidly progressing disease linked to a history of asbestos exposure in about 70% of cases. Patients with MPM often require multimodal treatment with surgery, radiotherapy, and adjuvant or neoadjuvant (presurgical) chemotherapy. The current standard of first-line chemotherapy for MPM is cisplatin or carboplatin in combination with pemetrexed, an antifolate compound that has been shown to increase the cytotoxic effects of platinum-based drugs. In Phase II and III clinical trials, combination therapy with pemetrexed and either cisplatin or carboplatin yielded some of the highest rates of tumor response (21-41%) and overall survival (about 12-14 months) reported to date. Dual-agent neoadjuvant chemotherapy (cisplatin plus gemcitabine or pemetrexed) followed by radical surgery with or without radiotherapy has been reported to yield median survival of up to 23-29 months in small clinical trials, but larger randomized controlled studies are needed to better define the role of neoadjuvant therapy in MPM management. Other chemotherapeutic agents that have been used against MPM, with variable results, include gemcitabine, vinorelbine, taxanes, anthracyclines, and molecular-targeted agents.

CONCLUSION: Treatment approaches for MPM include surgery, radiation, and systemic chemotherapy. MPM carries a poor prognosis, but recent studies of pemetrexed and platinum analogue combination therapies have demonstrated improved response rates over other treatments.}, } @article {pmid22343744, year = {2012}, author = {Kato, R and Matsuda, Y and Maehana, T and Miyao, N and Konishi, Y and Kon, S}, title = {[Intrascrotal malignant mesothelioma diagnosed after surgery for hydrocele testis: a case report].}, journal = {Hinyokika kiyo. Acta urologica Japonica}, volume = {58}, number = {1}, pages = {45-48}, pmid = {22343744}, issn = {0018-1994}, mesh = {Genital Neoplasms, Male/*diagnosis ; Humans ; Male ; Mesothelioma/*diagnosis ; Middle Aged ; *Scrotum ; Testicular Hydrocele/*surgery ; }, abstract = {We report here a case of intrascrotal malignant mesothelioma, arising from the tunica vaginalis, which was diagnosed after surgery for hydrocele testis. A 52-year-old man underwent left hydrocelectomy for hydrocele testis. After pathological diagnosis as malignant mesothelioma from the specimen of tunica vaginalis, left radical orchiectomy was performed. The patient had no exposure to asbestos and there has been no evidence of recurrence.}, } @article {pmid22329991, year = {2012}, author = {Fujii, M and Toyoda, T and Nakanishi, H and Yatabe, Y and Sato, A and Matsudaira, Y and Ito, H and Murakami, H and Kondo, Y and Kondo, E and Hida, T and Tsujimura, T and Osada, H and Sekido, Y}, title = {TGF-β synergizes with defects in the Hippo pathway to stimulate human malignant mesothelioma growth.}, journal = {The Journal of experimental medicine}, volume = {209}, number = {3}, pages = {479-494}, pmid = {22329991}, issn = {1540-9538}, mesh = {Animals ; Base Sequence ; Cell Cycle Proteins ; Cell Line, Tumor ; Cell Proliferation ; Connective Tissue Growth Factor/genetics ; DNA, Neoplasm/genetics ; Extracellular Matrix/physiology ; Female ; Gene Expression ; Genes, Neurofibromatosis 2 ; Humans ; Mesothelioma/genetics/pathology/*physiopathology ; Mice ; Mice, Nude ; Molecular Sequence Data ; Nuclear Proteins/physiology ; Promoter Regions, Genetic ; Signal Transduction ; Smad Proteins/physiology ; Transcription Factors/physiology ; Transcriptional Activation ; Transforming Growth Factor beta/*physiology ; }, abstract = {Malignant mesothelioma (MM) is an incurable malignancy that is caused by exposure to asbestos and is accompanied by severe fibrosis. Because MM is usually diagnosed at an advanced stage and clinical identification of early lesions is difficult, its molecular pathogenesis has not been completely elucidated. Nearly 75% of MM cases have inactivating mutations in the NF2 (neurofibromatosis type 2; Merlin) gene or in downstream signaling molecules of the Hippo signaling cascade, which negatively regulates the transcription factor Yes-associated protein (YAP). In this study, we demonstrate a functional interaction between the Hippo and TGF-β pathways in regulating connective tissue growth factor (CTGF). Expression of CTGF in MM cells was induced by the formation of a YAP-TEAD4-Smad3-p300 complex on the CTGF promoter. Knocking down CTGF expression in MM cells prolonged the survival of xenografted mice, and a significant association was seen between CTGF expression and extracellular matrix deposition in MM xenografts and in patient tissue specimens. We further suggest that CTGF may influence the malignancy of mesothelioma because of the different histological expression patterns observed in human MM tissues. These data suggest that CTGF is an important modulator of MM growth and pathology and represents a novel therapeutic target for this disease.}, } @article {pmid22324095, year = {2011}, author = {Davis, C and Vijaykumar, J and Lackovic, M and Diaz, JH}, title = {Asbestosis in Louisiana: a descriptive review and demographic analysis of hospitalizations for abestosis, 1999-2009.}, journal = {The Journal of the Louisiana State Medical Society : official organ of the Louisiana State Medical Society}, volume = {163}, number = {6}, pages = {336-341}, pmid = {22324095}, issn = {0024-6921}, support = {U60OH008470/OH/NIOSH CDC HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestosis/*epidemiology ; Databases, Factual ; Female ; Hospitalization/*statistics & numerical data ; Humans ; Louisiana/epidemiology ; Male ; Middle Aged ; Occupational Exposure/statistics & numerical data ; }, abstract = {Asbestosis is a debilitating, chronic, lung disease with no known treatment and most commonly occurs among workers in certain occupational settings. As a condition highly associated with occupational exposure, its incidence has been affected by changes in industry standards. In particular, the bans on both production and new uses of asbestos fibers put in place during the past 20 to 30 years have significantly reduced occupational exposures. Despite these restrictions, asbestos can still be found in many products. Louisiana has more facilities that produce, process, or use asbestos than any other state in the US. Health outcomes associated with asbestos exposure include asbestosis, mesothelioma, and lung cancer. To evaluate the impact of asbestos exposure on Louisiana residents, Louisiana Hospital Inpatient Discharge Data (LAHIDD) from 1999-2009 was analyzed. Results indicate that asbestosis hospitalizations have remained steady over the 11-year period with approximately 295 cases per year. White males have the highest rates, and cases are clustered geographically. Overall, Louisiana's rate is significantly greater than the US rate (p < 0.0001).}, } @article {pmid22321748, year = {2011}, author = {Shao, HJ and Ma, JT and Yang, XE and Xu, LP and Yang, CL}, title = {[Diagnostic and therapeutic analyses for peritoneal malignant mesothelioma: a report of 26 women].}, journal = {Zhonghua yi xue za zhi}, volume = {91}, number = {33}, pages = {2336-2339}, pmid = {22321748}, issn = {0376-2491}, mesh = {CA-125 Antigen ; Female ; Humans ; *Mesothelioma ; Omentum ; *Peritoneal Neoplasms ; Peritoneum ; }, abstract = {OBJECTIVE: To investigate the etiology, clinicopathologic features and prognosis of peritoneal malignant mesothelioma (PMM).

METHODS: The diagnostic and therapeutic data for PMM from March 2000 to December 2010 were retrospectively analyzed for 26 women. They had an age range of 41 - 78 years old. Among them, 21 patients (81%) had a history of exposure to asbestos. Their major symptoms were abdominal distension, abdominal pain, ascites and abdominopelvic mass. Some had cachexia. Intestinal obstruction occurred in all cases during a late stage.

RESULTS: Among them, the tumor marker of CA125 increased markedly in serum and ascitic samples. The positive rate of ascitic cytology was 31%. Type B ultrasound and CT (computed tomography) examinations showed ascites, peritoneal thickening and abdominopelvic mass and pie-shaped omentum. Their general pathological classifications were as follows: diffuse type (n = 23), localized type (n = 3), epithelial (n = 14), sarcoma (n = 3) and mixed type (n = 9). Cytoreductive surgery was performed in 16 cases. Ten patients underwent only laparoscopy while 23 patients received chemotherapy. The comparison of life span was not statistically significant between cytoreductive surgery and laparoscopy (P > 0.05); the difference of life span between ≤ 6 courses of chemotherapy and < 6 courses was not statistically significant (P > 0.05).

CONCLUSION: The history of exposure to asbestos is a risk factor for PMM. PMM with no specific clinical features should be combined with laboratory and imaging studies to make a timely clinical diagnosis. Final diagnosis should be based upon histopathological and immunohistochemical examinations. Surgery and chemotherapy do not prolong the life span of patients. And the patients have a very poor prognosis.}, } @article {pmid22321205, year = {2012}, author = {Mensi, C and Pellegatta, M and Sieno, C and Consonni, D and Riboldi, L and Bertazzi, PA}, title = {Mesothelioma of tunica vaginalis testis and asbestos exposure.}, journal = {BJU international}, volume = {110}, number = {4}, pages = {533-537}, doi = {10.1111/j.1464-410X.2012.10932.x}, pmid = {22321205}, issn = {1464-410X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*toxicity ; France/epidemiology ; Humans ; Incidence ; Kaplan-Meier Estimate ; Male ; Mesothelioma/*etiology/mortality ; Middle Aged ; Occupational Diseases/*etiology/mortality ; Registries ; *Serous Membrane ; Testicular Neoplasms/*etiology/mortality ; }, abstract = {UNLABELLED: Study Type - Therapy (case series). Level of Evidence 4. What's known on the subject? and What does the study add? Mesothelioma of the tunica vaginalis testis is a rare tumour. From 2000 to 2010, 13 mesothelioma of the tunica vaginalis testis cases were reported in the most populated and industrialized region in Italy. Asbestos exposure was documented in two-thirds of these cases.

OBJECTIVE: • To describe cases of mesothelioma of the tunica vaginalis testis (MTVT) recorded in the Lombardy Mesothelioma Registry between 2000 and 2010.

METHODS: • The Lombardy Mesothelioma Registry, established in 2000, collects data regarding all incident cases of mesothelioma of the pleura, peritoneum, pericardium and tunica vaginalis testis that have been diagnosed in the population of the Lombardy region. • These data include a detailed clinical report and a complete occupational history for each MTVT patient, with the latter including details of the industrial sector involved, the patient's job, and the specific tasks performed. To address the potential for asbestos exposure outside the work environment, the residential history, lifestyle habits and hobbies of the patient, as well as job information for all subjects living with the patient, are also collected. • Records were reviewed and discussed by a panel of experts.

RESULTS: • Thirteen cases of MTVT were reported between 2000 and 2010. • The age-standardized incidence rate of MTVT for the Lombardy region of Italy is 0.2 cases per million individuals/year. • Asbestos exposure was documented in 8 of the 12 (67%) interviewed cases.

CONCLUSIONS: • Asbestos exposure was associated with a higher proportion of MTVT cases than previously reported in the literature. These results confirm the aetiological role for asbestos in the pathogenesis of MTVT. • The results of this study also highlight the importance of obtaining detailed occupational histories and lifestyle habits from patients, particularly by trained interviewers.}, } @article {pmid22315054, year = {2012}, author = {Berry, G and Reid, A and Aboagye-Sarfo, P and de Klerk, NH and Olsen, NJ and Merler, E and Franklin, P and Musk, AW}, title = {Malignant mesotheliomas in former miners and millers of crocidolite at Wittenoom (Western Australia) after more than 50 years follow-up.}, journal = {British journal of cancer}, volume = {106}, number = {5}, pages = {1016-1020}, pmid = {22315054}, issn = {1532-1827}, mesh = {Asbestos, Crocidolite/*toxicity ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/diagnosis/epidemiology/mortality ; Male ; Mesothelioma/diagnosis/*epidemiology/mortality ; *Mining ; *Occupational Exposure ; Peritoneal Neoplasms/diagnosis/*epidemiology/mortality ; Pleural Neoplasms/diagnosis/*epidemiology/mortality ; Western Australia/epidemiology ; }, abstract = {BACKGROUND: To report the number of malignant pleural and peritoneal mesotheliomas that have occurred in former Wittenoom crocidolite workers to the end of 2008, to compare this with earlier predictions, and to relate the mesothelioma rate to amount of exposure.

METHODS: A group of 6489 men and 419 women who had worked for the company operating the former Wittenoom crocidolite mine and mill at some time between 1943 and 1966 have been followed up throughout Australia and Italy to the end of 2008.

RESULTS: The cumulative number of mesotheliomas up to 2008 was 316 in men (268 pleural, 48 peritoneal) and 13 (all pleural) in women. There had been 302 deaths with mesothelioma in men and 13 in women, which was almost 10% of all known deaths. Mesothelioma rate, both pleural and peritoneal, increased with time since first exposure and appeared to reach a plateau after about 40 to 50 years. The mesothelioma rate increased with amount of exposure and the peritoneal mesotheliomas occurred preferentially in the highest exposure group, 37% compared with 15% overall.

CONCLUSION: By the end of 2008, the number of mesothelioma deaths had reached 4.7% for all the male workers and 3.1% for the females. Over the past 8 years the numbers were higher than expected. It is predicted that about another 60 to 70 deaths with mesothelioma may occur in men by 2020.}, } @article {pmid22314851, year = {2012}, author = {La Vecchia, C and Boffetta, P}, title = {Role of stopping exposure and recent exposure to asbestos in the risk of mesothelioma.}, journal = {European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP)}, volume = {21}, number = {3}, pages = {227-230}, doi = {10.1097/CEJ.0b013e32834dbc56}, pmid = {22314851}, issn = {1473-5709}, mesh = {Age Factors ; Asbestos/*toxicity ; Carcinogens/*toxicity ; Cohort Studies ; Female ; Humans ; Male ; Mesothelioma/*etiology/mortality ; Occupational Diseases/*etiology/mortality ; Occupational Exposure/prevention & control/*statistics & numerical data ; Risk Assessment ; Time Factors ; }, abstract = {The model of asbestos-related mesothelioma implies that the time since first exposure (latency) is the key determinant of subsequent risk. The role of recent exposure or stopping asbestos exposure, if any, is, however, open to discussion. A literature review was conducted to the end of 2010. In a cohort of 1966 Italian textile workers, the standardized mortality ratio, on the basis of 68 deaths from mesothelioma, was 6627 for workers employed only under the age of 30 years, 8019 for those employed both under the age of 30 years and at the age of 30-39 years, and 5891 for those employed both under the age of 30 years and at the age of 40 years or more. In a cohort of Italian asbestos cement workers, including 135 deaths from pleural cancer, compared with workers who had stopped exposure for 3-15 years, the relative risk (RR) was similar for those still employed (RR=0.67) and for those who had stopped for 30 years or more (RR=0.65). In a British case-control study, including 622 cases of mesothelioma and 1420 population controls, the RR substantially increased with increasing duration of exposure under the age of 30 years, but not with exposure at the age of more than 30 years. In the Great Britain Asbestos Workers Survey, including 649 deaths from mesothelioma compared with workers who were still employed and or had stopped for less than 10 years, the multivariate RRs were 0.90 10-20 years after stopping exposure and 0.99 both 20-30 and more than 30 years after stopping. There is consistent evidence showing that, for workers exposed in the distant past, the risk of mesothelioma is not appreciably modified by subsequent exposures, and that stopping exposure does not materially modify the subsequent risk of mesothelioma.}, } @article {pmid22312960, year = {2011}, author = {Szubert, Z and Stankiewicz-Choroszucha, B and Wrońska-Sobolewska, M and Cwynar, E and Dobrowolska, J and Wróbel, R and Ratka, M and Jakubowski, J and Skórska-Ciszewska, I and Turbańska, R and Gazda, U and Sova, M and Pawłowska-Koziełł, H and Latala-Łoś, E and Komorowska, E and Sobala, W and Swiatkowska, B and Szeszenia-Dabrowska, N}, title = {[Implementation of the Amiantus project involving prophylactic medical examinations of the former employees of asbestos processing plants].}, journal = {Medycyna pracy}, volume = {62}, number = {5}, pages = {465-472}, pmid = {22312960}, issn = {0465-5893}, mesh = {Adult ; Aged, 80 and over ; Asbestosis/*diagnosis/epidemiology/prevention & control ; Environmental Monitoring/*statistics & numerical data ; Epidemiological Monitoring ; Female ; Health Plan Implementation ; Health Policy ; Humans ; Lung Neoplasms/epidemiology/*prevention & control ; Male ; Mass Screening/*methods ; Middle Aged ; National Health Programs/organization & administration ; Occupational Diseases/*prevention & control ; Occupational Exposure/*statistics & numerical data ; Poland ; Population Surveillance ; Public Health ; }, abstract = {BACKGROUND: Based on a 11-year implementation of the Amiantus Project, this paper reports the results of prophylactic medical examinations of the former workers of asbestos processing plants. The Project involving employees of 28 former asbestos plants was started by the Ministry of Health in 2000 under the Act on the ban of all products containing asbestos.

MATERIAL AND METHODS: Preventive examinations, continued in 13 centers of occupational medicine throughout the whole territory of Poland, have been coordinated by the Nofer Institute of Occupational Medicine in Lodz (NIOM). During the examinations, a specific Examination Form is filled-in by a physician. The Form is then sent to NIOM for monitoring health effects in the population covered by the Project. The results obtained by analyzing the lung radiological images are recorded in the Examination Form according to the ILO 1980 classification of pneumoconiosis. The diagnosis of the asbestos-related pathologies is based on the Helsinki criteria.

RESULTS: During the years 2000-2010, altogether 6,853 people were involved in the Project, and they were subjected to a total of 18,955 preventive examinations. Asbestosis was diagnosed in 1475 people, representing 21% of all respondents, lung cancer in 68 and mesothelioma in 40 people. Pleural radiographic changes were observed in 3027 (44%) patients, pulmonary parenchymal opacities in 4086 (60%) patients. The analysis showed that the asbestos-related pathologies were most frequent in the group of former employees of asbestos-cement plants. This group was also characterized by an age-, tenure-, and latency-related increasing trend in the prevalence of silicosis and the frequency of radiographic lesions in the lungs of those subjects.

CONCLUSIONS: The continuation of the examinations of former workers of asbestos processing industry has improved the detection of pathologies associated with exposure to asbestos and enabled undertaking an appropriate preventive action. The growing percentage of poorer radiography results reflects the progressive development of pathological processes in the respiratory system of people occupationally exposed to asbestos dust in the past.}, } @article {pmid22307011, year = {2012}, author = {Pinato, DJ and Mauri, FA and Ramakrishnan, R and Wahab, L and Lloyd, T and Sharma, R}, title = {Inflammation-based prognostic indices in malignant pleural mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {7}, number = {3}, pages = {587-594}, doi = {10.1097/JTO.0b013e31823f45c1}, pmid = {22307011}, issn = {1556-1380}, mesh = {Biomarkers, Tumor/*analysis ; Female ; Humans ; Immunoenzyme Techniques ; Inflammation/*blood/pathology ; Lymphocytes/*pathology ; Male ; Mesothelioma/*blood/pathology ; Neoplasm Staging ; Neutrophils/*pathology ; Pleural Neoplasms/*blood/pathology ; Prognosis ; Vascular Endothelial Growth Factor A/blood ; }, abstract = {INTRODUCTION: Chronic inflammation plays a key role in the pathogenesis of malignant pleural mesothelioma (MPM) as a result of asbestos exposure. Biomarkers of systemic inflammation have been shown to predict the natural history of MPM; however, this observation lacks independent validation. Our aim was to compare the prognostic performance of three inflammation-based biomarkers in predicting overall survival (OS) in MPM.

METHODS: In patients with histologically proven MPM, the inflammation-based prognostic scores modified Glasgow Prognostic Score (mGPS), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio were studied and compared with the European Organization for the Research and Treatment of Cancer Prognostic Score (EPS) and other known potential prognostic factors such as gender, histologic subtype, Eastern Cooperative Oncology Group performance status, and baseline blood parameters.

RESULTS: A total of 171 MPM patients presenting to Imperial College NHS Trust were studied. In univariate analyses, the following parameters were predictors of OS: female gender (p = 0.03), epithelioid histology (p = 0.03), normal C-reactive protein (p = 0.03), baseline white blood cell count <8.3 × 10/liter (p = 0.04), EPS (p = 0.003), mGPS (p < 0.001), NLR (p = 0.006), and platelet-to-lymphocyte ratio (p = 0.03). Multivariate survival analysis confirmed the mGPS (hazard ratio = 2.6; p < 0.001) and NLR (hazard ratio = 2.0; p = 0.008), but not the EPS, as independent predictors of OS. Tissue expression of Ki-67 (p < 0.001) and vascular endothelial growth factor (p < 0.001) was higher in a subgroup of patients with high-risk inflammatory scores.

CONCLUSIONS: The mGPS and NLR are externally validated prognostic indices in patients with MPM and correlate with sustained neoangiogenesis and increased proliferative index.}, } @article {pmid22292488, year = {2012}, author = {Robinson, C and Woo, S and Walsh, A and Nowak, AK and Lake, RA}, title = {The antioxidants vitamins A and E and selenium do not reduce the incidence of asbestos-induced disease in a mouse model of mesothelioma.}, journal = {Nutrition and cancer}, volume = {64}, number = {2}, pages = {315-322}, doi = {10.1080/01635581.2012.649100}, pmid = {22292488}, issn = {1532-7914}, mesh = {Animals ; Anticarcinogenic Agents ; Antigens, Polyomavirus Transforming/genetics ; Antioxidants/*administration & dosage ; *Asbestos/administration & dosage ; Diet ; Dietary Supplements ; Disease Models, Animal ; GPI-Linked Proteins/genetics ; Injections, Intraperitoneal ; Mesothelin ; Mesothelioma/chemically induced/*prevention & control ; Mice ; Mice, Transgenic ; Promoter Regions, Genetic/genetics ; Selenium/*administration & dosage/blood ; Vitamin A/*administration & dosage/blood ; Vitamin E/*administration & dosage/blood ; }, abstract = {Epidemiological evidence indicates that supplementation with some dietary factors is associated with a lower incidence of cancer. An effective cancer prevention strategy for the millions of people worldwide who have been exposed to asbestos could have enormous benefit. We tested whether dietary supplementation of the antioxidants vitamin A, E, and selenium could alter the pattern of disease in the MexTAg transgenic mouse model, in which mice uniformly develop mesothelioma after asbestos exposure. We focused on antioxidants because one of the most widely accepted hypotheses for the mechanism by which asbestos fibers cause cancer proposes the involvement of reactive oxygen and nitrogen species. We compared the survival of MexTAg mice that had been inoculated with asbestos fed on diets supplemented with 250,000 IU/kg vitamin A (retinoic acid), or 1,000 mg/kg vitamin E (α-tocopherol acetate) or 3 mg/kg selenium, or both vitamin E and selenium concurrently and, additionally, diets deficient in each antioxidant. We found that neither the time to develop symptoms of disease nor overall survival times were altered by any of the diets. We conclude that the data do not support the notion that dietary antioxidants will moderate the rate of mesothelioma in asbestos-exposed populations.}, } @article {pmid22283446, year = {2012}, author = {Egilman, D}, title = {Report of a recent "brake" through in the fiber burden-mesothelioma dialogue.}, journal = {Inhalation toxicology}, volume = {24}, number = {2}, pages = {136-137}, doi = {10.3109/08958378.2011.643932}, pmid = {22283446}, issn = {1091-7691}, mesh = {Asbestos, Amphibole/*chemistry/*toxicity ; Asbestos, Serpentine/*chemistry/*toxicity ; Humans ; Lung/*chemistry ; }, } @article {pmid22282545, year = {2012}, author = {Riaz, SP and Coupland, VH and Lüchtenborg, M and Peake, MD and Møller, H}, title = {Mesothelioma incidence projections in South East England.}, journal = {The European respiratory journal}, volume = {40}, number = {4}, pages = {965-968}, doi = {10.1183/09031936.00168111}, pmid = {22282545}, issn = {1399-3003}, support = {//Department of Health/United Kingdom ; }, mesh = {Asbestos/adverse effects ; Cohort Studies ; England/epidemiology ; Female ; Forecasting ; Humans ; Incidence ; Male ; Mesothelioma/*epidemiology/etiology ; Occupational Exposure/adverse effects/*statistics & numerical data ; Pleural Neoplasms/*epidemiology/etiology ; Sex Factors ; }, abstract = {We estimated the past and future age-standardised incidence rates of mesothelioma by birth cohort and by period of diagnosis in South East England. We extracted data on patients diagnosed with mesothelioma (International Classification of Diseases-10 C45) between 1960 and 2009 from the Thames Cancer Registry. We calculated the age-standardised incidence rates using the European standard population. We used age-cohort and age-period modelling to estimate the age-specific incidence rates for the 1900 to 1950 birth cohorts and the 1935 to 2034 calendar periods. A much more pronounced increase in mesothelioma incidence between 1972 and 2007 was observed in males than in females. In both sexes, the incidence rates increased in successive generations up to the 1945 birth cohort. Projection of rates in the future showed an increase in incidence in males until 2022 and a decrease thereafter. Among females, the incidence rate was predicted to increase gradually until reaching its maximum around 2027, and to remain stable thereafter. The occurrence of mesothelioma is closely linked to occupational exposure to asbestos in the 1960s and 1970s and, due to the long latency period, the incidence of mesothelioma is projected to increase until the 2020s.}, } @article {pmid22275923, year = {2011}, author = {Carkanat, AI and Abdurrahman, A and Abakay, O and Cengizhan, S and Selimoglu, SH and Senyigit, A}, title = {The incidence of mesothelioma has not decreased for the last twenty years in Southeast region of Anatolia.}, journal = {African health sciences}, volume = {11}, number = {3}, pages = {346-352}, pmid = {22275923}, issn = {1729-0503}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Female ; Humans ; Incidence ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Pleural Neoplasms/chemically induced/*epidemiology ; Retrospective Studies ; Turkey/epidemiology ; Young Adult ; }, abstract = {BACKGROUND: Malignant pleural Mesothelioma (MPM) is a very rarely encountered tumor in the normal population.

OBJECTIVES: To investigate the variations in incidence of MPM in Southeast region of Turkey.

METHODS: We retrospectively investigated the data of 161 MPM patients who were diagnosed from January 2000 to December 2009. The residential areas were determined according to asbestos exposure which plays a role in MPM etiology; previously reported as having asbestos (Region 1) and asbestos has not been determined previously (Region 2).

RESULTS: One hundred nine (109) of the patients (67.7%) included from the Region 1 and 52 of them (32.3%) included from the Region 2. MPM incidence of the last decade was 3.9/100,000 person/year for the whole region. In Region 1, 2000-2004 incidences was 12.6/100,000 person/year and 2005-2009 incidences was 14.9/100,000 person/year. In Region 2, 2000-2004 incidences was 0.4/100,000 person/year and 2005-2009 incidences was 1.0/100,000 person/year. According to the recently conducted incidence studies in our region, MPM incidence increased in region 1 and decreased in region 2. The number of patients applying to our hospital has increased in the last three years.

CONCLUSION: This increase, in Region 1 may be associated with continuous use of asbestos.}, } @article {pmid22271370, year = {2012}, author = {Murakami, A and Fujimori, Y and Yoshikawa, Y and Yamada, S and Tamura, K and Hirayama, N and Terada, T and Kuribayashi, K and Tabata, C and Fukuoka, K and Tamaoki, T and Nakano, T}, title = {Heme oxygenase-1 promoter polymorphism is associated with risk of malignant mesothelioma.}, journal = {Lung}, volume = {190}, number = {3}, pages = {333-337}, pmid = {22271370}, issn = {1432-1750}, mesh = {Aged ; Aged, 80 and over ; Alleles ; Asbestos/adverse effects ; Female ; Gene Frequency ; *Genetic Predisposition to Disease ; Genotype ; Heme Oxygenase-1/*genetics ; Humans ; Male ; Mesothelioma/etiology/*genetics ; Middle Aged ; Pleural Neoplasms/etiology/*genetics ; *Polymorphism, Genetic ; *Promoter Regions, Genetic ; Risk Factors ; }, abstract = {BACKGROUND: Malignant mesothelioma is an aggressive tumor of serosal surfaces that is closely associated with asbestos exposure which induces oxidative stress. Heme oxygenase (HO)-1, a rate-limiting enzyme of heme degradation, plays a protective role against oxidative stress. The HO-1 gene promoter carries (GT)n repeats whose number is inversely related to transcriptional activity of the HO-1 gene.

METHODS: To investigate the relationship between the length polymorphism of (GT)n repeats and mesothelioma susceptibility, we analyzed the HO-1 promoter in 44 asbestos-exposed subjects without mesothelioma and 78 asbestos-exposed subjects with mesothelioma using PCR-based genotyping.

RESULTS: The number of repeats ranged from 16 to 38, with two peaks at 23 and 30 repeats. Polymorphisms of (GT)n repeats were grouped into two classes of alleles, short (S) (<24) and long (L) (≥24), and three genotypes: L/L, L/S, and S/S. The proportions of allele frequencies in class L as well as genotypic frequencies of L allele carriers (L/L and L/S) were significantly higher in the asbestos-exposed subjects with mesothelioma than in those without mesothelioma.

CONCLUSION: The findings of this study suggest that long (GT)n repeats in the HO-1 gene promoter are associated with a higher risk of malignant mesothelioma in the Japanese population.}, } @article {pmid22253921, year = {2012}, author = {Weber, DG and Johnen, G and Bryk, O and Jöckel, KH and Brüning, T}, title = {Identification of miRNA-103 in the cellular fraction of human peripheral blood as a potential biomarker for malignant mesothelioma--a pilot study.}, journal = {PloS one}, volume = {7}, number = {1}, pages = {e30221}, pmid = {22253921}, issn = {1932-6203}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos ; Biomarkers, Tumor/*blood ; Blood Cells/*metabolism ; Case-Control Studies ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Male ; Mesothelioma/*blood/*genetics ; MicroRNAs/*blood/genetics/metabolism ; Middle Aged ; Pilot Projects ; ROC Curve ; }, abstract = {BACKGROUND: To date, no biomarkers with reasonable sensitivity and specificity for the early detection of malignant mesothelioma have been described. The use of microRNAs (miRNAs) as minimally-invasive biomarkers has opened new opportunities for the diagnosis of cancer, primarily because they exhibit tumor-specific expression profiles and have been commonly observed in blood of both cancer patients and healthy controls. The aim of this pilot study was to identify miRNAs in the cellular fraction of human peripheral blood as potential novel biomarkers for the detection of malignant mesothelioma.

Using oligonucleotide microarrays for biomarker identification the miRNA levels in the cellular fraction of human peripheral blood of mesothelioma patients and asbestos-exposed controls were analyzed. Using a threefold expression change in combination with a significance level of p<0.05, miR-103 was identified as a potential biomarker for malignant mesothelioma. Quantitative real-time PCR (qRT-PCR) was used for validation of miR-103 in 23 malignant mesothelioma patients, 17 asbestos-exposed controls, and 25 controls from the general population. For discrimination of mesothelioma patients from asbestos-exposed controls a sensitivity of 83% and a specificity of 71% were calculated, and for discrimination of mesothelioma patients from the general population a sensitivity of 78% and a specificity of 76%.

CONCLUSIONS/SIGNIFICANCE: The results of this pilot study show that miR-103 is characterized by a promising sensitivity and specificity and might be a potential minimally-invasive biomarker for the diagnosis of mesothelioma. In addition, our results support the concept of using the cellular fraction of human blood for biomarker discovery. However, for early detection of malignant mesothelioma the feasibility of miR-103 alone or in combination with other biomarkers needs to be analyzed in a prospective study.}, } @article {pmid22251266, year = {2012}, author = {Cyphert, JM and Padilla-Carlin, DJ and Schladweiler, MC and Shannahan, JH and Nyska, A and Kodavanti, UP and Gavett, SH}, title = {Long-term response of rats to single intratracheal exposure of Libby amphibole or amosite.}, journal = {Journal of toxicology and environmental health. Part A}, volume = {75}, number = {3}, pages = {183-200}, doi = {10.1080/15287394.2012.641203}, pmid = {22251266}, issn = {1528-7394}, mesh = {Animals ; Asbestos, Amosite/*toxicity ; Asbestos, Amphibole/*toxicity ; Biomarkers ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Environmental Exposure ; ErbB Receptors/genetics/metabolism ; Fibrosis/pathology ; GPI-Linked Proteins/genetics/metabolism ; Gene Expression Regulation ; Genes, Wilms Tumor/drug effects ; Inflammation/pathology ; Lung/drug effects/pathology ; Male ; Mesothelin ; Rats ; Rats, Inbred F344 ; }, abstract = {In former mine workers and residents of Libby, Montana, exposure to amphibole-contaminated vermiculite has been associated with increased incidences of asbestosis and mesothelioma. In this study, long-term effects of Libby amphibole (LA) exposure were investigated relative to the well-characterized amosite asbestos in a rat model. Rat-respirable fractions of LA and amosite (aerodynamic diameter≤2.5 μm) were prepared by water elutriation. Male F344 rats were exposed to a single dose of either saline, amosite (0.65 mg/rat), or LA (0.65 or 6.5 mg/rat) by intratracheal (IT) instillation. One year after exposure, asbestos-exposed rats displayed chronic pulmonary inflammation and fibrosis. Two years postexposure, lung inflammation and fibrosis progressed in a time- and dose-dependent manner in LA-exposed rats, although the severity of inflammation and fibrosis was smaller in magnitude than in animals exposed to amosite. In contrast, gene expression of the fibrosis markers Col 1A2 and Col 3A1 was significantly greater in LA-exposed compared to amosite-exposed rats. There was no apparent evidence of preneoplastic changes in any of the asbestos-exposed groups. However, all asbestos-exposed rats demonstrated a significant increase in the expression of epidermal growth factor receptor (EGFR) 2 yr after instillation. In addition, only LA-exposed rats showed significant elevation in mesothelin (Msln) and Wilms' tumor gene (WT1) expression, suggesting possible induction of tumor pathways. These results demonstrate that a single IT exposure to LA is sufficient to induce significant fibrogenic, but not carcinogenic, effects up to 2 yr after exposure that differ both in quality and magnitude from those elicited by amosite administration at the same mass dose in F344 rats. Data showed that LA was on a mass basis less potent than amosite.}, } @article {pmid22248252, year = {2012}, author = {Takahashi, K and Eves, ND and Piper, A and Song, Y and Maher, TM}, title = {Year in review 2011: acute lung injury, interstitial lung diseases, physiology, sleep and lung cancer.}, journal = {Respirology (Carlton, Vic.)}, volume = {17}, number = {3}, pages = {554-562}, doi = {10.1111/j.1440-1843.2012.02127.x}, pmid = {22248252}, issn = {1440-1843}, mesh = {Acute Lung Injury/*diagnosis/therapy ; Adenocarcinoma/*diagnosis/etiology/therapy ; Adenocarcinoma of Lung ; Air Pollution/adverse effects ; Asbestos/toxicity ; Cough/diagnosis/therapy ; Humans ; Lung Diseases, Interstitial/complications/*diagnosis/etiology/therapy ; Lung Neoplasms/*diagnosis/etiology/therapy ; Mesothelioma/diagnosis/etiology/therapy ; Pulmonary Disease, Chronic Obstructive/diagnosis/etiology/therapy ; Risk Factors ; Sarcoidosis/diagnosis/therapy ; Sleep/*physiology ; }, } @article {pmid22247179, year = {2012}, author = {Barbieri, PG and Mirabelli, D and Somigliana, A and Cavone, D and Merler, E}, title = {Asbestos fibre burden in the lungs of patients with mesothelioma who lived near asbestos-cement factories.}, journal = {The Annals of occupational hygiene}, volume = {56}, number = {6}, pages = {660-670}, doi = {10.1093/annhyg/mer126}, pmid = {22247179}, issn = {1475-3162}, mesh = {Adult ; Asbestos, Amphibole/*analysis ; Construction Materials/*toxicity ; Female ; Humans ; Inhalation Exposure/*adverse effects ; Italy ; *Lung Neoplasms ; Male ; *Mesothelioma ; Microscopy, Electron, Scanning ; Middle Aged ; Mineral Fibers/*toxicity ; Occupational Exposure/adverse effects ; Residence Characteristics ; }, abstract = {BACKGROUND: Epidemics of malignant mesothelioma are occurring among inhabitants of Casale Monferrato and Bari never employed in the local asbestos-cement (AC) factories. The mesothelioma risk increased with proximity of residence to both plants.

OBJECTIVES: To provide information on the intensity of environmental asbestos exposure, in the general population living around these factories, through the evaluation of the lung fibre burden in mesothelioma patients.

METHODS: We analysed by a scanning electron microscope equipped with X-ray microanalysis wet (formalin-fixed) lung tissue samples from eight mesothelioma patients who lived in Casale Monferrato or Bari and underwent surgery. Their occupational and residential history was obtained during face-to-face interviews. Semi-quantitative and quantitative indices of cumulative environmental exposure to asbestos were computed, based on residential distance from the AC plants and duration of stay.

RESULTS: The lung fibre burden ranged from 110 000 to 4 300 000 fibres per gram of dry lung (f/g) and was >1 000 000 f/g in three subjects. In four cases, only amphibole fibres were detected. Environmental exposures had ceased at least 10 years before samples were taken. No patient had other definite or probable asbestos exposures. A linear relationship was observed between the lung fibre burden and all three indices of environmental cumulative exposure to asbestos.

CONCLUSIONS: Environmental exposure to a mixture of asbestos fibres may lead to a high lung fibre burden of amphiboles years after exposure cessation. The epidemiological evidence of an increased mesothelioma risk for the general population of Casale Monferrato and Bari, associated with asbestos contamination of the living environment, is corroborated.}, } @article {pmid22237902, year = {2012}, author = {Gramond, C and Rolland, P and Lacourt, A and Ducamp, S and Chamming's, S and Creau, Y and Hery, M and Laureillard, J and Mohammed-Brahim, B and Orlowski, E and Paris, C and Pairon, JC and Goldberg, M and Brochard, P and , }, title = {Choice of rating method for assessing occupational asbestos exposure: study for compensation purposes in France.}, journal = {American journal of industrial medicine}, volume = {55}, number = {5}, pages = {440-449}, doi = {10.1002/ajim.22008}, pmid = {22237902}, issn = {1097-0274}, mesh = {*Asbestos/analysis ; Case-Control Studies ; *Compensation and Redress ; Female ; France/epidemiology ; Humans ; Male ; Mesothelioma/*epidemiology ; Occupational Diseases/*epidemiology ; Occupational Exposure/analysis/*classification ; Occupations/statistics & numerical data ; Probability ; Reproducibility of Results ; Risk Assessment/*methods ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: In the course of setting up the National Mesothelioma Surveillance Program (PNSM), established in France in 1998, the question arose as to the most suitable method of assessing occupational exposure. The aim of this study was to define the most suitable rating method for assessing occupational asbestos exposure in order to assess medico-social care.

METHOD: The study included 100 subjects-50 cases of mesothelioma and 50 controls-randomly selected and representing 457 jobs held. Job asbestos exposure was assessed by a six-expert panel using two methods: "by job" rating, where all the jobs in were assessed regardless of the subjects; and "by subject" rating, where all the jobs of a subject were assessed at the same time. Consensus was obtained and subjects' exposure was calculated for each rating. Then, two internal experts assessed job asbestos exposure with the "by subject" rating. Kappa coefficients were used to measure agreement between the ratings.

RESULTS: Agreement between "by job" and "by subject" ratings was very good for subject probability of exposure (kappa = 0.84) and cumulative exposure index (kappa = 0.80). Agreement between the six-expert panel and the two internal experts was good for subject exposure (kappa for probability = 0.71; kappa for cumulative exposure index= 0.68).

CONCLUSION: This study shows that the two rating systems have good or very good agreement. These results validate the routine use in the PNSM of the "by subject" rating, with the advantage of being convenient and quick to provide feedback on occupational asbestos exposure to mesothelioma cases for compensation.}, } @article {pmid22237727, year = {2012}, author = {Tsujimura, T and Torii, I and Sato, A and Song, M and Fukuoka, K and Hasegawa, S and Nakano, T}, title = {Pathological and molecular biological approaches to early mesothelioma.}, journal = {International journal of clinical oncology}, volume = {17}, number = {1}, pages = {40-47}, pmid = {22237727}, issn = {1437-7772}, mesh = {Biomarkers, Tumor/genetics/*metabolism ; *Early Detection of Cancer ; Genes, p16 ; Humans ; Mesothelioma/genetics/*metabolism/*pathology ; Neoplasm Staging ; Neurofibromin 2/genetics/metabolism ; Pleural Effusion, Malignant/pathology ; Pleural Neoplasms/genetics/*metabolism/*pathology ; Tumor Suppressor Proteins/genetics/metabolism ; Ubiquitin Thiolesterase/genetics/metabolism ; }, abstract = {Malignant mesothelioma is an asbestos-related malignancy that arises primarily from mesothelial cells on the serosal surfaces of the pleural, peritoneal, and pericardial cavities. Malignant pleural mesothelioma (MPM) is most common, and its incidence is dramatically increasing worldwide as a result of widespread use of asbestos. Morphological discrimination between MPM and reactive mesothelial hyperplasia is difficult, and the most reliable pathological criterion for malignancy is mesothelial proliferation invading deeply into subpleural adipose tissues. To establish radical cure of MPM, it is crucial to find early-stage MPM of epithelial type, in which mesothelial proliferation is localized on the serosal surface of parietal pleura or limited within the submesothelial fibrous tissues of parietal pleura. The initial clinical presentation for patients with MPM is frequently dyspnea and/or chest pain due to large pleural effusion, and cytological analysis of pleural effusions is valuable to find patients with early-stage MPM of epithelial type. Recently, cytological features of MPM in pleural effusion, molecular markers for MPM, and genetic alternations of MPM have been reported. In this review, we discuss major issues on pathological and molecular biological approaches for diagnosis of early-stage MPM of epithelial type.}, } @article {pmid22237142, year = {2011}, author = {Ghawanmeh, T and Thunberg, U and Castro, J and Murray, F and Laytragoon-Lewin, N}, title = {miR-34a expression, cell cycle arrest and cell death of malignant mesothelioma cells upon treatment with radiation, docetaxel or combination treatment.}, journal = {Oncology}, volume = {81}, number = {5-6}, pages = {330-335}, doi = {10.1159/000334237}, pmid = {22237142}, issn = {1423-0232}, mesh = {Antineoplastic Agents/pharmacology ; Cell Cycle/drug effects/genetics/radiation effects ; Cell Cycle Checkpoints/*drug effects/genetics/*radiation effects ; Cell Death/drug effects/genetics/radiation effects ; Cell Line, Tumor ; Combined Modality Therapy/methods ; Docetaxel ; Humans ; Mesothelioma/*drug therapy/genetics/pathology/*radiotherapy ; MicroRNAs/*biosynthesis/genetics ; Radiation-Sensitizing Agents/pharmacology ; Taxoids/*pharmacology ; Tumor Suppressor Protein p53/biosynthesis/genetics ; }, abstract = {OBJECTIVE: Malignant mesothelioma (MM) is a highly aggressive tumour related to asbestos exposure. Histopathologically, the tumour is classified as epithelial, sarcomatoid or biphasic. To date, MM is still an incurable disease.

METHODS: To evaluate treatment strategies on MM cells, the effects of radiotherapy, docetaxel or a combination of both on MM cells derived from the sarcomatoid type ZL34 and the epithelial type M28K were investigated. The TP53 gene, micro-RNA expression, cell cycle distribution and cell death were assessed as indicators of treatment effects.

RESULTS: Despite the normal TP53 gene sequences in these cell lines, radiation-induced miR-34a expression was detected only in the M28K cells. Increasing G0/G1 cell numbers were detected in irradiated M28K and ZL34 cells. There was more radiation-induced cell death in M28K compared to ZL34 cells. The highest degree of cell cycle arrest at G2 and cell death in both cell types was obtained in the presence of docetaxel. The combination of docetaxel and radiation did not show any additive effects on miR-34a expression, cell cycle arrest or cell death in either the M28K or ZL34 cells.

CONCLUSION: Microtubule formation and other related functions by docetaxel might be the most suitable treatment modulation in both sarcomatoid and epithelial types of MM.}, } @article {pmid22233924, year = {2012}, author = {McCormack, V and Peto, J and Byrnes, G and Straif, K and Boffetta, P}, title = {Estimating the asbestos-related lung cancer burden from mesothelioma mortality.}, journal = {British journal of cancer}, volume = {106}, number = {3}, pages = {575-584}, pmid = {22233924}, issn = {1532-1827}, mesh = {Asbestos/*toxicity ; Carcinogens/*toxicity ; Cohort Studies ; Global Health ; Humans ; Lung Neoplasms/chemically induced/*mortality/pathology ; Mesothelioma/chemically induced/*mortality/pathology ; Models, Biological ; Mortality ; Tumor Burden ; United Kingdom/epidemiology ; United States/epidemiology ; }, abstract = {BACKGROUND: Quantifying the asbestos-related lung cancer burden is difficult in the presence of this disease's multiple causes. We explore two methods to estimate this burden using mesothelioma deaths as a proxy for asbestos exposure.

METHODS: From the follow-up of 55 asbestos cohorts, we estimated ratios of (i) absolute number of asbestos-related lung cancers to mesothelioma deaths; (ii) excess lung cancer relative risk (%) to mesothelioma mortality per 1000 non-asbestos-related deaths.

RESULTS: Ratios varied by asbestos type; there were a mean 0.7 (95% confidence interval 0.5, 1.0) asbestos-related lung cancers per mesothelioma death in crocidolite cohorts (n=6 estimates), 6.1 (3.6, 10.5) in chrysotile (n=16), 4.0 (2.8, 5.9) in amosite (n=4) and 1.9 (1.4, 2.6) in mixed asbestos fibre cohorts (n=31). In a population with 2 mesothelioma deaths per 1000 deaths at ages 40-84 years (e.g., US men), the estimated lung cancer population attributable fraction due to mixed asbestos was estimated to be 4.0%.

CONCLUSION: All types of asbestos fibres kill at least twice as many people through lung cancer than through mesothelioma, except for crocidolite. For chrysotile, widely consumed today, asbestos-related lung cancers cannot be robustly estimated from few mesothelioma deaths and the latter cannot be used to infer no excess risk of lung or other cancers.}, } @article {pmid22222641, year = {2012}, author = {Ordóñez, NG}, title = {Mesotheliomas with small cell features: report of eight cases.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {25}, number = {5}, pages = {689-698}, doi = {10.1038/modpathol.2011.202}, pmid = {22222641}, issn = {1530-0285}, mesh = {Aged ; Asbestos/adverse effects ; Biomarkers, Tumor/metabolism ; Combined Modality Therapy ; Epithelioid Cells/metabolism/*pathology ; Female ; Humans ; Male ; Mesothelioma/etiology/metabolism/mortality/*pathology ; Middle Aged ; Pleural Neoplasms/etiology/metabolism/mortality/*pathology ; Pneumonectomy ; Survival Rate ; Texas/epidemiology ; }, abstract = {Mesotheliomas with small cell morphology are rare and only one study of such cases has been published. As a result of their rare occurrence, some investigators have cast doubt on the existence of such a histologic variant of mesothelioma. This investigator reports a series of eight cases of epithelioid mesothelioma with small cell features, all of which originated in the pleura. Seven of the patients were men and one was a woman. Four patients had a history of asbestos exposure. Histologically, four of the mesotheliomas were epithelioid and four biphasic. The proportion of small cells seen in these cases constituted 80 to 100% of the tumor included in the biopsy material and 15 to 20% of the tumor present in the pneumonectomy specimens. Immunoreactivity for calretinin, keratin 5/6, keratin 7, pan-keratin, WT1, podoplanin, and mesothelin was seen in all cases tested for these markers. All of the cases were negative for MOC-31, Ber-EP4, CEA, CD15, TAG-72, TTF-1, chromogranin A, synaptophysin, CD99, and desmin. The mean survival of the six patients for whom this information was available was 8.2 months. It is important for pathologists to be aware that mesotheliomas can present small cell features and, because of this, they can be confused with other malignancies that can exhibit similar morphology. The value of immunohistochemistry in the differential diagnosis of these tumors is discussed.}, } @article {pmid22200078, year = {2011}, author = {Franke, K and Paustenbach, D}, title = {Government and Navy knowledge regarding health hazards of asbestos: a state of the science evaluation (1900 to 1970).}, journal = {Inhalation toxicology}, volume = {23 Suppl 3}, number = {}, pages = {1-20}, doi = {10.3109/08958378.2011.643417}, pmid = {22200078}, issn = {1091-7691}, mesh = {Asbestos/*adverse effects ; Asbestosis/*etiology ; Environmental Monitoring ; *Health Knowledge, Attitudes, Practice ; Humans ; Naval Medicine ; Occupational Exposure/*adverse effects ; Ships ; United States ; *United States Department of Defense ; }, abstract = {We evaluated dozens of published and unpublished documents describing the knowledge and awareness of both the scientific community and governmental entities, particularly the US Navy, regarding the health hazards associated with asbestos over time. We divided our analysis into specific blocks of time: 1900-1929, 1930-1959, and 1960-1970. By 1930, it was clear that high occupational exposure to asbestos caused a unique disease (asbestosis). Between about 1938 and 1965, a considerable amount of exposure and epidemiology data were collected by various scientific and government organizations. Between 1960 and 1970, mesothelioma was clearly linked to exposure to amphibole asbestos. Nonetheless, the Navy continued to require the use of asbestos-containing materials on ships, but also recommended that proper precautions be taken when handling asbestos. We concluded that the Navy was arguably one of the most knowledgeable organizations in the world regarding the health hazards of asbestos, and that it attempted to implement procedures that would minimize the opportunity for adverse effects on both servicemen and civilians. Finally, it is apparent from our research that through at least 1970, neither the military nor the private sector believed that the myriad of asbestos-containing products considered "encapsulated" (e.g. gaskets, brakes, Bakelite) posed a health hazard to those working with them.}, } @article {pmid22210814, year = {2012}, author = {Gogali, A and Manda-Stachouli, C and Ntzani, EE and Matthaiou, M and Konstantinidis, AK and Zampira, I and Koubaniou, C and Dalavanga, Y and Stefanou, D and Constantopoulos, SH and Daskalopoulos, G}, title = {Malignant mesothelioma in Metsovo, Greece, from domestic use of asbestos: 30 years later.}, journal = {The European respiratory journal}, volume = {39}, number = {1}, pages = {217-219}, doi = {10.1183/09031936.00017011}, pmid = {22210814}, issn = {1399-3003}, mesh = {Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Environmental Exposure ; Female ; Follow-Up Studies ; Greece ; Humans ; Incidence ; Male ; Mesothelioma/*epidemiology/*etiology ; Middle Aged ; Pleural Neoplasms/*epidemiology/*etiology ; Risk ; Time Factors ; }, } @article {pmid25048089, year = {2012}, author = {Sheff, KW and Hoda, MA and Dome, B and Hegedus, B and Klepetko, W and Weiss, GJ}, title = {The role of microRNAs in the diagnosis and treatment of malignant pleural mesothelioma--a short review.}, journal = {MicroRNA (Shariqah, United Arab Emirates)}, volume = {1}, number = {1}, pages = {40-48}, doi = {10.2174/2211536611201010040}, pmid = {25048089}, issn = {2211-5374}, mesh = {Antineoplastic Agents/therapeutic use ; Biomarkers, Tumor/genetics/metabolism ; Humans ; Lung Neoplasms/*diagnosis/*therapy ; Mesothelioma/*diagnosis/*therapy ; Mesothelioma, Malignant ; MicroRNAs/*genetics/*therapeutic use ; Pleural Neoplasms/*diagnosis/*therapy ; Prognosis ; Treatment Outcome ; }, abstract = {MicroRNAs are a class of small, non-coding RNAs that can function as tumor suppressors or oncogenes by regulating gene expression. This link was first reported in 2004, and has since been tied to a variety of malignancies, including malignant pleural mesothelioma (MPM). MPM is a malignancy arising in the mesothelial cells lining the lung pleura and is associated with chronic asbestos exposure. Despite the possibility for observing declining localized occurrence, global MPM is predicted to remain constant or increase slightly over the next decade. Global occurrence in combination with poor overall survival, difficulty in diagnosis, and limited effective treatment options signal the need for further exploration of miRNA involvement in MPM. Accordingly, this review highlights miRNA profiles associated with the diagnosis, prognosis, and therapeutic approaches in MPM.}, } @article {pmid24960130, year = {2012}, author = {Abdelrahman, M and Dowling, C and O'Connor, K and Mayer, N and Kiely, E}, title = {Malignant mesothelioma of the tunica vaginalis.}, journal = {Journal of surgical case reports}, volume = {2012}, number = {5}, pages = {2}, pmid = {24960130}, issn = {2042-8812}, abstract = {Malignant mesothelioma of the tunica vaginalis is a rare but potentially fatal disease. Lack of characteristic clinical features and tumour markers makes the pre-operative diagnosis very difficult. A 54 year-old man with no history of exposure to asbestos presented with a short history of scrotal swelling and pain. Ultrasound revealed a suspicious nodularity involving his tunica vaginalis, suggestive of mesothelioma. Excisional biopsy revealed a malignant mesothelioma; hence the patient was treated with radical inguinal orchidectomy and hemiscrotectomy. We present a case of this rare tumour, its management and a review of the literature.}, } @article {pmid22202589, year = {2011}, author = {Egilman, DS and Ardolino, EL and Howe, S and Bird, T}, title = {Deconstructing a state-of-the-art review of the asbestos brake industry.}, journal = {New solutions : a journal of environmental and occupational health policy : NS}, volume = {21}, number = {4}, pages = {545-571}, doi = {10.2190/NS.21.4.e}, pmid = {22202589}, issn = {1541-3772}, mesh = {*Asbestos/adverse effects ; *Bias ; *Industry ; Mesothelioma/etiology ; Occupational Exposure/legislation & jurisprudence ; *Review Literature as Topic ; Truth Disclosure ; }, abstract = {State of the art is a legal concept that describes what was known as knowable by experts including manufacturer's state of knowledge about the potential hazards of their product(s) at a point in time. In 2004, Paustenbach et al. published a state-of-the-art review that describes the development of knowledge about asbestos hazards to brake mechanics performing asbestos brake installation and maintenance. Paustenbach et al.'s review, however, omits important pieces of corporate knowledge, dismisses several historical scientific conclusions and ignores the way experts have applied the results of scientific research to protect workers and consumers handling asbestos brakes. By taking their state-of-the-art review out of the legal liability context, Paustenbach et al. create a misleading version of events that fails to properly address the question of what asbestos brake manufacturers knew or should have known about the potential hazards of their brakes to mechanics over time. Without proper presentation of this information, judges and juries cannot adequately assess whether these companies had a duty to warn or take other action to prevent injury to those exposed to their asbestos brakes.}, } @article {pmid22166300, year = {2011}, author = {Marinaccio, A and Binazzi, A and Di Marzio, D and Massari, S and Scarselli, A and Iavicoli, S}, title = {[The contribution of surveillance systems of occupational diseases and mesothelioma in environmental health studies].}, journal = {Epidemiologia e prevenzione}, volume = {35}, number = {5-6 Suppl 4}, pages = {185-188}, pmid = {22166300}, issn = {1120-9763}, mesh = {Adenocarcinoma/epidemiology/etiology ; Asbestos/adverse effects ; Disease Notification/*methods/standards ; Environmental Health/*methods ; Environmental Pollution/*adverse effects/statistics & numerical data ; Female ; Hazardous Substances/adverse effects ; Hazardous Waste/*adverse effects/statistics & numerical data ; Humans ; Industrial Waste/*adverse effects/statistics & numerical data ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology ; Nose Neoplasms/epidemiology/etiology ; Occupational Diseases/*epidemiology ; Occupational Exposure ; Occupational Medicine/*organization & administration/standards ; Paranasal Sinus Neoplasms/epidemiology/etiology ; Pleural Neoplasms/*epidemiology ; Population Surveillance/*methods ; Registries/standards/*statistics & numerical data ; Urban Health ; }, abstract = {National surveillance systems of occupational diseases may contribute to evaluate the work-related component of diseases investigated in SENTIERI Project. For a description of SENTIERI, refer to the 2010 Supplement of Epidemiology & Prevention devoted to SENTIERI Project. The National Workers Compensation Authority (INAIL) archives all occupational diseases claims (more than 230 000 in the period 2000-2007) and is in charge of their compensation. The Italian National Mesothelioma Register (ReNaM) and the Sinonasal Cancer Register (ReNaTuNS) record high occupational etiological fraction neoplasms (i.e. mesothelioma and sinonasal cancers). The former has identified more than 10 000 mesothelioma cases until now, and covers almost the whole country; the latter is active only in three Italian regions, Piemonte, Lombardia and Toscana. The monitoring of cancer sites at lower occupational etiological fraction is based on a record-linkage procedure between population-based cancer registries and employment history data, available at the Italian National Institute for Social Security (INPS). Finally, the informative system Mal.Prof collects and classifies all the diseases possibly related to the work environment reported by the Prevention Services of the Local Health Units.}, } @article {pmid22166295, year = {2011}, author = {Pirastu, R and Zona, A and Ancona, C and Bruno, C and Fano, V and Fazzo, L and Iavarone, I and Minichilli, F and Mitis, F and Pasetto, R and Comba, P}, title = {[Mortality results in SENTIERI Project].}, journal = {Epidemiologia e prevenzione}, volume = {35}, number = {5-6 Suppl 4}, pages = {29-152}, pmid = {22166295}, issn = {1120-9763}, mesh = {Asbestos/adverse effects ; Cardiovascular Diseases/mortality ; Causality ; Congenital Abnormalities/mortality ; Digestive System Diseases/mortality ; Environmental Exposure ; Environmental Pollution/*adverse effects/statistics & numerical data ; Female ; Female Urogenital Diseases/mortality ; Hazardous Substances/adverse effects ; Hazardous Waste/*adverse effects/statistics & numerical data ; Humans ; Industrial Waste/*adverse effects/statistics & numerical data ; Italy/epidemiology ; Male ; Male Urogenital Diseases/mortality ; Mesothelioma/etiology/mortality ; Mineral Fibers/adverse effects ; *Mortality ; Neoplasms/mortality ; Nervous System Diseases/chemically induced/mortality ; Organic Chemicals/adverse effects ; Pleural Neoplasms/etiology/mortality ; *Population Surveillance ; Respiratory Tract Diseases/mortality ; Urban Health/statistics & numerical data ; }, abstract = {SENTIERI Project (Mortality study of residents in Italian polluted sites) studies mortality of residents in 44 sites of national interest for environmental remediation (Italian polluted sites, IPS). The epidemiological evidence of the causal association between causes of death and exposures was a priori classified into one of these three categories: Sufficient (S), Limited (L) and Inadequate (I). In these sites various environmental exposures are present. Asbestos (or asbestiform fibres as in Biancavilla) has been the motivation for defining six sites as IPSs (Balangero, Emarese, Casale Monferrato, Broni, Bari-Fibronit, Biancavilla). In five of these, increases in malignant neoplasm or pleura mortality are detected; in four of them, results are consistent in both genders. In six other sites (Pitelli, Massa Carrara, Aree del Litorale Vesuviano, Tito, "Aree industriali della Val Basento", Priolo), where other sources of environmental pollution in addition to asbestos are reported, mortality from malignant neoplasm of pleura is increased in both genders in Pitelli, Massa Carrara, Priolo, "Litorale vesuviano". In the time span 1995-2002, a total of 416 extra cases of malignant neoplasm of pleura are detected in the twelve asbestos-polluted sites. Asbestos and pleural neoplasm represent an unique case. Unlike mesothelioma, most causes of death analyzed in SENTIERI have multifactorial etiology; furthermore, in most IPSs multiple sources of different pollutants are present, sometimes concurrently with air pollution from urban areas: in these cases, drawing conclusions on the association between environmental exposures and specific health outcomes might be complicated. Notwithstanding these difficulties, in a number of cases an etiological role could be attributed to some environmental exposures. The attribution could be possible on the basis of increases observed in both genders and in different age classes, and the exclusion of a major role of occupational exposures was thus allowed. For example, a role of emissions from refineries and petrochemical plants was hypothesized for the observed increases in mortality from lung cancer and respiratory diseases in Gela and Porto Torres; a role of emissions from metal industries was suggested to explain increased mortality from respiratory diseases in Taranto and in Sulcis-Iglesiente-Guspinese. An etiological role of air pollution in the raise in congenital anomalies and perinatal disorders was suggested in Falconara Marittima, Massa-Carrara, Milazzo and Porto Torres. A causal role of heavy metals, PAH's and halogenated compounds was suspected for mortality from renal failure in Massa Carrara, Piombino, Orbetello, "Basso bacino del fiume Chienti" and Sulcis-Iglesiente-Guspinese. In Trento-Nord, Grado and Marano, and "Basso bacino del fiume Chienti" increases in neurological diseases, for which an etiological role of lead, mercury and organohalogenated solvents is possible, were reported. The increase for non-Hodgkin lymphomas in Brescia was associated with the widespread PCB pollution. Mortality for causes of death with a priori Sufficient or Limited evidence of association with the environmental exposure exceeds the expected figures, with a SMR of 115.8% for men (90% IC 114.4-117.2; 2 439 extra deaths) and 114.4% for women (90% CI 112.4-116.5; 1 069 extra deaths). These excesses are also observed when analysis is extended to all the causes of death (i.e. with no restriction to the ones with a priori Sufficient or Limited evidence): for a total of 403 692 deaths (both men and women), an excess of 9 969 deaths is observed, with an average of about 1 200 extra deaths per year. Most of these excesses are observed in IPSs located in Southern and Central Italy. The procedures and results of the evidence evaluation are presented in a 2010 Supplement of Epidemiology & Prevention devoted to SENTIERI.}, } @article {pmid22183490, year = {2012}, author = {Chapman, EA and Thomas, PS and Stone, E and Lewis, C and Yates, DH}, title = {A breath test for malignant mesothelioma using an electronic nose.}, journal = {The European respiratory journal}, volume = {40}, number = {2}, pages = {448-454}, doi = {10.1183/09031936.00040911}, pmid = {22183490}, issn = {1399-3003}, mesh = {Aged ; Asbestos/metabolism ; Biomarkers/metabolism ; Breath Tests/*instrumentation/*methods ; Carbon/chemistry ; Case-Control Studies ; Cross-Sectional Studies ; Female ; Forced Expiratory Volume ; Humans ; Lung/physiology ; Lung Diseases/*diagnosis ; Male ; Mesothelioma/*diagnosis ; Middle Aged ; Polymers/chemistry ; Principal Component Analysis ; Reproducibility of Results ; Sensitivity and Specificity ; Spirometry ; Surveys and Questionnaires ; Volatile Organic Compounds ; }, abstract = {Malignant mesothelioma (MM) is a rare tumour which is difficult to diagnose in its early stages. Earlier detection of MM could potentially improve survival. Exhaled breath sampling of volatile organic compounds (VOCs) using a carbon polymer array (CPA) electronic nose recognises specific breath profiles characteristic of different diseases, and can distinguish between patients with lung cancer and controls. With MM, the potential confounding effect of other asbestos-related diseases (ARDs) needs to be considered. We hypothesised that as CPA electronic nose would distinguish patients with MM, patients with benign ARDs, and controls with high sensitivity and specificity. 20 MM, 18 ARD and 42 control subjects participated in a cross-sectional, case-control study. Breath samples were analysed using the Cyranose 320 (Smiths Detection, Pasadena, CA, USA), using canonical discriminant analysis and principal component reduction. 10 MM subjects created the training set. Smell prints from 10 new MM patients were distinguished from control subjects with an accuracy of 95%. Patients with MM, ARDs and control subjects were correctly identified in 88% of cases. Exhaled breath VOC profiling can accurately distinguish between patients with MM, ARDs and controls using a CPA electronic nose. This could eventually translate into a screening tool for high-risk populations.}, } @article {pmid22166780, year = {2011}, author = {Merler, E and Bressan, V and Bilato, AM and Marinaccio, A and , }, title = {[The effectiveness of compensation system for mesotheliomas due to occupational exposure to asbestos and determinants for requests and awards: an evaluation based on record-linkage between the Veneto Mesothelioma Register and the claims and compensations recorded by the National Insurance Institute (INAIL)].}, journal = {Epidemiologia e prevenzione}, volume = {35}, number = {5-6}, pages = {331-338}, pmid = {22166780}, issn = {1120-9763}, mesh = {Academies and Institutes/statistics & numerical data ; Aged ; Asbestos/*adverse effects ; Female ; Humans ; Insurance Benefits/*statistics & numerical data ; Insurance Claim Reporting/statistics & numerical data ; *Insurance Claim Review ; Italy/epidemiology ; Male ; *Medical Record Linkage ; Mesothelioma/*economics/epidemiology/etiology ; Middle Aged ; *Occupational Exposure ; Occupations ; Pleural Neoplasms/*economics/epidemiology/etiology ; Prejudice ; Program Evaluation ; Registries/statistics & numerical data ; Socioeconomic Factors ; Workers' Compensation/economics/standards/*statistics & numerical data ; }, abstract = {AIM: To determine the rate of requests for compensation and of compensations awarded for mesothelioma cases due to occupational exposure to asbestos; to identify factors that may influence the outcome; to provide an appreciation of the amount of compensation.

Record-linkage study at individual level between the new cases of mesothelioma occurred among the residents of the Veneto Region (Northern Italy) between 1999- 2007 and the file of the Insurance Institute, with individual data on all claims and compensations. Adjusted logistic regression models were used to estimated the association between submitting claims and obtaining an award and socio-demographic and other characteristics.

RESULTS: 349 on 499 mesotheliomas considered to be due to occupational exposure to asbestos submitted a claim (70% of those of occupational origin) and 72%of claims were accepted. The welfare system covers only 35%of mesothelioma occurred. The probability of submitting and obtaining a claim was associated with gender, cancer site, age at diagnosis, vital status, and residence or local office in charge of the evaluation. A strong discrimination against women is observed. If exposure to asbestos at work was due to a direct manipulation of asbestos, claims were more easily accepted.As a consequence,mesothelioma occurred among construction workers, the occupational activity at the origin of the largest number of occurring mesotheliomas, are more frequently rejected.When submitted by a relative, the lag between a request for compensation and the decision is on average of about two years.

CONCLUSION: This is the first study in Italy using a record-linkage method and was made possible thanks to a population based mesothelioma Register and the availability of memorized information of the Insurance Institute.The welfare system shown clear limitations and there is the need for more appropriate strategies.}, } @article {pmid22164014, year = {2011}, author = {Cho, MO and Yoon, S and Han, H and Kim, JK}, title = {Automated counting of airborne asbestos fibers by a high-throughput microscopy (HTM) method.}, journal = {Sensors (Basel, Switzerland)}, volume = {11}, number = {7}, pages = {7231-7242}, pmid = {22164014}, issn = {1424-8220}, mesh = {Asbestos/*analysis ; High-Throughput Screening Assays/*methods ; Image Processing, Computer-Assisted/methods ; Microscopy, Phase-Contrast/*methods ; Particulate Matter/*analysis ; }, abstract = {Inhalation of airborne asbestos causes serious health problems such as lung cancer and malignant mesothelioma. The phase-contrast microscopy (PCM) method has been widely used for estimating airborne asbestos concentrations because it does not require complicated processes or high-priced equipment. However, the PCM method is time-consuming and laborious as it is manually performed off-site by an expert. We have developed a high-throughput microscopy (HTM) method that can detect fibers distinguishable from other spherical particles in a sample slide by image processing both automatically and quantitatively. A set of parameters for processing and analysis of asbestos fiber images was adjusted for standard asbestos samples with known concentrations. We analyzed sample slides containing airborne asbestos fibers collected at 11 different workplaces following PCM and HTM methods, and found a reasonably good agreement in the asbestos concentration. Image acquisition synchronized with the movement of the robotic sample stages followed by an automated batch processing of a stack of sample images enabled us to count asbestos fibers with greatly reduced time and labors. HTM should be a potential alternative to conventional PCM, moving a step closer to realization of on-site monitoring of asbestos fibers in air.}, } @article {pmid22152932, year = {2011}, author = {Dalphin, JC}, title = {[Follow-up of subjects occupationally exposed to asbestos, what are the objectives, the benefits, and the possible risks?].}, journal = {Revue des maladies respiratoires}, volume = {28}, number = {10}, pages = {1230-1240}, doi = {10.1016/j.rmr.2011.06.015}, pmid = {22152932}, issn = {1776-2588}, mesh = {Asbestos/*adverse effects ; Asbestosis/epidemiology/etiology ; Canada/epidemiology ; Carcinoma/epidemiology/etiology ; Diagnostic Techniques, Respiratory System/adverse effects/economics/psychology/statistics & numerical data ; Early Diagnosis ; Europe/epidemiology ; Follow-Up Studies ; Humans ; Lung Neoplasms/epidemiology/etiology ; Mesothelioma/epidemiology/etiology ; *Occupational Exposure ; Pleural Diseases/epidemiology/etiology ; Pleural Neoplasms/epidemiology/etiology ; *Population Surveillance/methods ; Radiography, Thoracic/adverse effects ; Risk Assessment ; Smoking ; Stress, Psychological/etiology ; World Health Organization ; }, abstract = {The follow-up of workers occupationally exposed to asbestos has two possible beneficial effects: (1) individually, both medical by screening for diseases related to asbestos and social by notification of occupational disease and/or compensation from the indemnity funds for asbestos victims; (2) collectively, by the establishment of epidemiological surveillance (follow-up of cohorts) and evaluation of the impact of follow-up in terms of health benefits and compensation. The respiratory disorders related to asbestos are: cancer (malignant pleural mesothelioma and bronchial carcinoma), asbestos-related pulmonary fibrosis, and pleural disease (plaques, pleural fibrosis and benign pleurisy). In the light of the data currently available and the effectiveness of the tools used, medical and public health benefits of screening for mesothelioma have not been demonstrated. The early diagnosis of primary bronchial carcinoma can theoretically improve the prognosis of the subjects screened, particularly by identification of stage I disease on CT (pulmonary nodules). This is a common finding but there are a large number of false-positives. While we await the results of several international randomised trials, the benefits of a screening programme for bronchial carcinoma in the population at risk have not been demonstrated. There is no effective treatment for asbestosis but this is an independent risk factor for bronchial carcinoma and it is evidence of heavy asbestos exposure. Stopping smoking in subjects suffering from asbestosis will reduce the incidence of bronchial carcinoma. There is no effective treatment for asbestos-related benign pleural diseases but these are markers of exposure. The presence of pleural plaques has not been shown to be an aetiological factor for thoracic cancers. Post-occupational follow-up may involve risks to health, particularly repeated irradiation and invasive diagnostic procedures. It is also necessary to consider the psychological consequences inherent in all screening programmes. In conclusion, post-occupational follow-up might reduce the mortality of lung cancer by screening for localised disease and its incidence by a targeted anti-smoking programme. The theoretical benefits, that have not yet been demonstrated, have to be seen in perspective with the risks to physical and psychological health related to both screening and diagnostic procedures.}, } @article {pmid22146010, year = {2012}, author = {Fujii, M and Fujimoto, N and Hiraki, A and Gemba, K and Aoe, K and Umemura, S and Katayama, H and Takigawa, N and Kiura, K and Tanimoto, M and Kishimoto, T}, title = {Aberrant DNA methylation profile in pleural fluid for differential diagnosis of malignant pleural mesothelioma.}, journal = {Cancer science}, volume = {103}, number = {3}, pages = {510-514}, pmid = {22146010}, issn = {1349-7006}, mesh = {Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Body Fluids ; DNA Methylation/*genetics ; *DNA, Neoplasm/genetics ; Diagnosis, Differential ; Female ; Gene Expression Profiling ; Humans ; Lung Neoplasms/*diagnosis/genetics ; Male ; Mesothelioma/chemically induced/*diagnosis/genetics ; Middle Aged ; Pleural Neoplasms/chemically induced/*diagnosis/genetics ; Promoter Regions, Genetic/genetics ; Real-Time Polymerase Chain Reaction ; }, abstract = {Malignant pleural mesothelioma (MPM) usually develops pleural fluid. We investigated the value of DNA methylation in the pleural fluid for differentiating MPM from lung cancer (LC). Pleural fluid was collected from 39 patients with MPM, 46 with LC, 25 with benign asbestos pleurisy (BAP) and 30 with other causes. The methylation of O(6)-methylguanine-DNA methyltransferase (MGMT), p16(INK4a) , ras association domain family 1A (RASSF1A), death-associated protein kinase (DAPK), and retinoic acid receptor β (RARβ) was examined using quantitative real-time PCR. DNA methylation of RASSF1A, p16(INK4a), RARβ, MGMT and DAPK was detected in 12 (30.8%), 3 (7.7%), 11 (28.2%), 0 (0.0%) and five patients (12.8%) with MPM, and in 22 (47.8%), 14 (30.4%), 24 (52.2%), 1 (2.2%) and six patients (13.0%) with LC, respectively. The mean methylation ratios of RASSF1A, p16(INK4a) and RARβ were 0.37 (range 0.0-2.84), 0.11 (0.0-2.67) and 0.44 (0.0-3.32) in MPM, and 0.87 (0.0-3.14), 1.16 (0.0-5.35) and 1.69 (0.0-6.49) in LC, respectively. The methylation ratios for the three genes were significantly higher in LC than in MPM (RASSF1A, P = 0.039; p16(INK4a), P = 0.005; and RARβ, P = 0.002). Patients with methylation in at least one gene were 3.51 (95% confidence interval, 1.09-11.34) times more likely to have LC. Hypermethylation seemed no greater with MPM than with BAP. Extended exposure to asbestos (≧30 years) was correlated with an increased methylation frequency (P = 0.020). Hypermethylation of tumor suppressor genes in pleural fluid DNA has the potential to be a valuable marker for differentiating MPM from LC.}, } @article {pmid22141364, year = {2012}, author = {Finley, BL and Pierce, JS and Phelka, AD and Adams, RE and Paustenbach, DJ and Thuett, KA and Barlow, CA}, title = {Evaluation of tremolite asbestos exposures associated with the use of commercial products.}, journal = {Critical reviews in toxicology}, volume = {42}, number = {2}, pages = {119-146}, doi = {10.3109/10408444.2011.636028}, pmid = {22141364}, issn = {1547-6898}, mesh = {Aluminum Silicates/analysis/toxicity ; Animals ; Asbestos, Amphibole/analysis/*toxicity ; Asbestos, Serpentine/analysis/*toxicity ; Humans ; Incidence ; Lung Neoplasms/chemically induced/epidemiology ; Mesothelioma/chemically induced/*epidemiology ; Occupational Diseases/chemically induced/*epidemiology ; Occupational Exposure/*analysis ; Risk Assessment ; Talc/analysis/toxicity ; Toxicity Tests/methods ; }, abstract = {Tremolite is a noncommercial form of amphibole mineral that is present in some chrysotile, talc, and vermiculite deposits. Inhalation of asbestiform tremolite is suspected to have caused or contributed to an increased incidence of mesothelioma in certain mining settings; however, very little is known about the magnitude of tremolite exposure that occurred at these locations, and even less is known regarding tremolite exposures that might have occurred during consumer use of chrysotile, talc, and vermiculite containing products. The purpose of this analysis is to evaluate the exposure-response relationship for tremolite asbestos and mesothelioma in high exposure settings (mining) and to develop estimates of tremolite asbestos exposure for various product use scenarios. Our interpretation of the tremolite asbestos exposure metrics reported for the Thetford chrysotile mines and the Libby vermiculite deposits suggests a lowest-observed-adverse-effect level (LOAEL) for mesothelioma of 35-73 f/cc-year. Using measured and estimated airborne tremolite asbestos concentrations for simulated and actual product use, we conservatively estimated the following cumulative tremolite asbestos exposures: career auto mechanic: 0.028 f/cc-year; non-occupational use of joint compound: 0.0006 f/cc-year; non-occupational use of vermiculite-containing gardening products: 0.034 f/cc-year; home-owner removal of Zonolite insulation: 0.0002 f/cc-year. While the estimated consumer tremolite exposures are far below the tremolite LOAELs derived herein, this analysis examines only a few of the hundreds of chrysotile- and talc-containing products.}, } @article {pmid22129857, year = {2012}, author = {Chen, M and Tse, LA and Au, RK and Yu, IT and Wang, XR and Lao, XQ and Au, JS}, title = {Mesothelioma and lung cancer mortality: a historical cohort study among asbestosis workers in Hong Kong.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {76}, number = {2}, pages = {165-170}, doi = {10.1016/j.lungcan.2011.11.003}, pmid = {22129857}, issn = {1872-8332}, mesh = {Aged ; Asbestosis/*mortality ; Cohort Studies ; Follow-Up Studies ; Heart Diseases/mortality ; Hong Kong/epidemiology ; Humans ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; Occupational Diseases/*mortality ; Occupational Exposure/statistics & numerical data ; Smoking/adverse effects ; }, abstract = {OBJECTIVES: To investigate the mortality pattern among a cohort of workers with asbestosis in Hong Kong, with special emphases on mesothelioma and lung cancer.

METHODS: All 124 male workers with confirmed asbestosis in Hong Kong during 1981-2008 were followed up to December 31, 2008 to ascertain the vital status and causes of death. Standardized mortality ratio (SMR) for each underlying cause of death was calculated by using person-year method. Axelson's indirect method was applied to adjust for the potential confounding effect of cigarette smoking.

RESULTS: A total of 86 deaths were observed after 432.8 person-years of observations. The SMR for overall mortality (6.06, 95% CI: 4.90-7.51) increased significantly. The elevated risk of deaths from all cancers (7.53, 95% CI: 5.38-10.25) was mainly resulted from a significantly excess risk from lung cancer (SMR=7.91, 95% CI: 4.32-13.29, 14 deaths) and mesothelioma (SMR=6013.63, 95% CI: 3505.95-9621.81, 17 deaths). The SMR for lung cancer retained statistically significant after adjustment of smoking. An increased smoking adjusted SMR was also suggested for all heart diseases (2.32, 95% CI: 0.93-4.79, 7 deaths) and acute myocardial infarction (3.10, 95% CI: 0.84-7.94, 4 deaths), though the statistical significance was borderline. We found a positive association with net years of exposure to asbestos for mesothelioma and lung cancer.

CONCLUSIONS: Our study provided further evidence on the carcinogenesis of asbestos/asbestosis with the risk of deaths from lung cancer and mesothelioma. This study also provided a preliminary support for a possible link between asbestosis and heart disease, but power is limited.}, } @article {pmid22126592, year = {2012}, author = {Gemba, K and Fujimoto, N and Kato, K and Aoe, K and Takeshima, Y and Inai, K and Kishimoto, T}, title = {National survey of malignant mesothelioma and asbestos exposure in Japan.}, journal = {Cancer science}, volume = {103}, number = {3}, pages = {483-490}, pmid = {22126592}, issn = {1349-7006}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Female ; Humans ; Japan/epidemiology ; Male ; Mesothelioma/*chemically induced/*epidemiology/pathology ; Middle Aged ; Young Adult ; }, abstract = {In the present study, malignant mesothelioma (MM) cases in Japan were investigated retrospectively. We extracted records for 6030 cases of death due to MM between 2003 and 2008 to clarify the clinical features of MM, including its association with asbestos exposure (AE). Of all these cases, a clinical diagnosis of MM was confirmed for 929. The origin of MM included the pleura in 794 cases (85.5%), the peritoneum in 123 cases (13.2%), the pericardium in seven cases (0.8%), and the testicular tunica vaginalis in five cases (0.5%). The histological subtypes of MM included 396 epithelioid (55.9%), 154 sarcomatoid (21.7%), 126 biphasic (17.8%), and 33 cases (4.7%) classified as "other types". Of all the MM cases, AE was indicated in 76.8% and pleural plaques were detected in 34.2%. The number of asbestos particles was determined in 103 cases of MM. More than 1000 asbestos particles per gram dried lung tissue were detected in 74.8% of cases and more than 5000 particles were detected in 43.7% of cases. We compared patient characteristics and the diagnostic procedures for MM before and after the "Kubota shock". Compared with the early phase of this study (2003-2005), the median age at diagnosis of MM was higher, the number of cases without definite diagnosis of MM was lower, the proportion of cases diagnosed by thoracoscopy was higher, and the percentage of cases in which the occupational history was described in the medical records was significantly higher in the later phase (2006-2008). Our study confirmed that more than 70% of MM cases in Japan are associated with AE. The "Kubota shock" may affect some features pertaining to MM.}, } @article {pmid22118184, year = {2011}, author = {Clin, B and Luc, A and Morlais, F and Paris, C and Ameille, J and Brochard, P and De Girolamo, J and Gislard, A and Laurent, F and Letourneux, M and Schorle, E and Launoy, G and Pairon, JC and , }, title = {Pulmonary nodules detected by thoracic computed tomography scan after exposure to asbestos: diagnostic significance.}, journal = {The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease}, volume = {15}, number = {12}, pages = {1707-1714}, pmid = {22118184}, issn = {1815-7920}, mesh = {Aged ; Asbestos/*toxicity ; Carcinogens/toxicity ; Female ; Humans ; Incidence ; Lung Neoplasms/chemically induced/*diagnostic imaging/pathology ; Male ; Mass Screening/methods ; Mesothelioma/chemically induced/diagnostic imaging/pathology ; Middle Aged ; Multiple Pulmonary Nodules/diagnostic imaging/pathology ; Occupational Exposure/adverse effects ; Pleural Neoplasms/chemically induced/*diagnostic imaging/pathology ; Population Surveillance ; Prevalence ; Solitary Pulmonary Nodule/diagnostic imaging/pathology ; Tomography, X-Ray Computed/*methods ; }, abstract = {OBJECTIVE: To analyse the relationship between pulmonary nodules detected by radiologists using computed tomography and cumulative exposure to asbestos or asbestos-related pleuro-pulmonary diseases in 5662 asbestos-exposed subjects, and the relationship between pulmonary nodules and thoracic cancer, to determine whether a specific surveillance strategy based on cumulative asbestos exposure should be adopted.

DESIGN: Standardised incidence and mortality ratios (SIR) for lung cancer and pleural mesothelioma were calculated in patients with and without mention of pulmonary nodules and compared using comparative morbidity figures.

RESULTS: A significant excess incidence of primary lung cancer and pleural mesothelioma was observed among subjects presenting with pulmonary nodule(s) (SIR respectively 1.95, 95%CI 1.22-2.95, and 11.88, 95%CI 3.20-30.41). However, there was no significant relationship between pulmonary nodules mentioned by radiologists and cumulative asbestos exposure or between pulmonary nodules and the presence of asbestos-related benign diseases.

CONCLUSIONS: This study confirms the expected excess prevalence of lung cancer in subjects presenting with pulmonary nodules according to the radiologist's report, and shows the absence of relationship between the presence of nodules and level of cumulative asbestos exposure. Our study therefore offers no argument in favour of specific surveillance modalities based on estimated cumulative asbestos exposure.}, } @article {pmid22112531, year = {2011}, author = {Vuskovic, MI and Xu, H and Bovin, NV and Pass, HI and Huflejt, ME}, title = {Processing and analysis of serum antibody binding signals from Printed Glycan Arrays for diagnostic and prognostic applications.}, journal = {International journal of bioinformatics research and applications}, volume = {7}, number = {4}, pages = {402-426}, doi = {10.1504/IJBRA.2011.043771}, pmid = {22112531}, issn = {1744-5485}, support = {U01CA111295/CA/NCI NIH HHS/United States ; U01CA128526/CA/NCI NIH HHS/United States ; }, mesh = {Antibodies/*blood ; Asbestos/toxicity ; Biomarkers/blood ; Case-Control Studies ; Humans ; Mesothelioma/diagnosis/etiology/mortality ; Microarray Analysis/*methods ; Polysaccharides/*chemistry/immunology ; Predictive Value of Tests ; Survival Analysis ; }, abstract = {Procedures for data preprocessing, quality control, data analysis, evaluation and visualization of the new high-throughput biomarker platform based on printed glycan arrays (PGA) are presented in this paper. PGAs are similar in concept to DNA arrays but contain deposits of various carbohydrate structures (glycans) instead of spotted DNAs. PGA biomarker discovery for the early detection, diagnosis and prognosis of human malignancies and viral diseases is based on the response of the immune system as measured by the level of binding of anti-glycan antibodies from human serum to the glycans on the array. Procedures related to PGA data processing are herein demonstrated in a pilot study of cases representing 50 sera from patients with malignant mesothelioma and a control sample of 65 sera from high risk subjects exposed to asbestos without symptoms of disease.}, } @article {pmid22104079, year = {2012}, author = {Mirarabshahii, P and Pillai, K and Chua, TC and Pourgholami, MH and Morris, DL}, title = {Diffuse malignant peritoneal mesothelioma--an update on treatment.}, journal = {Cancer treatment reviews}, volume = {38}, number = {6}, pages = {605-612}, doi = {10.1016/j.ctrv.2011.10.006}, pmid = {22104079}, issn = {1532-1967}, mesh = {Combined Modality Therapy ; Humans ; Mesothelioma/diagnosis/mortality/*therapy ; Peritoneal Neoplasms/diagnosis/mortality/*therapy ; Prognosis ; }, abstract = {Mesotheliomas are aggressive and lethal neoplasms arising from mesothelial cells lining the pleura, peritoneum, tunica vaginalis testis and pericardium. Malignant peritoneal mesothelioma accounts for about 30% of all mesotheliomas. Asbestos is the main known cause of the disease. Presenting symptoms in these patients include: ascites, abdominal pain, asthenia, weight loss, anorexia, abdominal mass, fever, diarrhea and vomiting. Electron microscopy, immunohistochemistry, computed tomography scan, echotomography, magnetic resonance imaging, positron emission tomography and laparoscopy are used in diagnosis and follow-up. Chemotherapy alone is considered as a palliative treatment for these patients who are not eligible for radical surgery. The most promising non-surgical approach today in the management of peritoneal mesothelioma is the use of the combination chemotherapy regime of an antifolate (pemetrexed and raltitrexed) and a platinum based (cisplatin) agent with a median survival of about 12-14 months. Due to peritoneal confinement of malignant mesothelioma and low occurrence of metastasis, a locoregional approach consisting of cytoreductive surgery and perioperative intraperitoneal chemotherapy has been introduced as a curative treatment option over the last decade with an overall 5-year survival rate of 29-63%. In this locoregional approach, surgery can separate the adhesions and remove the bulky tumor, leaving microscopic residual tumors much more susceptible to the killing effect of chemotherapeutic drugs. Here in St. George hospital, cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (using cisplatin and doxorubicin) resulted in significant survival advantage. This article describes how the prognosis of the disease has changed over the last decade.}, } @article {pmid22095628, year = {2012}, author = {Niu, K and Asada, M and Okazaki, T and Yamanda, S and Ebihara, T and Guo, H and Zhang, D and Nagatomi, R and Arai, H and Kohzuki, M and Ebihara, S}, title = {Adiponectin pathway attenuates malignant mesothelioma cell growth.}, journal = {American journal of respiratory cell and molecular biology}, volume = {46}, number = {4}, pages = {515-523}, doi = {10.1165/rcmb.2011-0068OC}, pmid = {22095628}, issn = {1535-4989}, mesh = {AMP-Activated Protein Kinase Kinases ; Adiponectin/blood/*metabolism/pharmacology ; Animals ; Apoptosis/drug effects ; Cell Proliferation/drug effects ; Cyclooxygenase 2/metabolism ; Diet ; Fish Oils/pharmacology ; Gene Expression Regulation, Neoplastic ; Humans ; Male ; Mesothelioma/diet therapy/*metabolism/*pathology ; Mice ; Mice, Inbred Strains ; Mice, SCID ; Protein Kinases/metabolism ; Receptors, Adiponectin/genetics/metabolism ; Signal Transduction ; Xenograft Model Antitumor Assays ; }, abstract = {Malignant mesothelioma (MM) is caused by exposure to asbestos. Because MM has a latency period, short survival time, and has a poor response to current therapeutic regimes, long-term preventive strategies are required to suppress the advance of pathological states after asbestos exposure. Accumulating evidence suggests that adiponectin plays a crucial role in the regulation of energy metabolism by increasing AMP-activated protein kinase (AMPK) activation. Several studies have indicated that the activation of AMPK decreases cyclooxygenase (COX)-2 expression. Because high COX-2 levels correlated with a worse prognosis and survival rate in MM, we examined whether the adiponectin pathway suppresses MM cell growth through the AMPK/COX-2 pathway. In vivo, dietary fish oil (a potential promoter of adiponectin) decreased the growth rate of MM, which was accompanied by an increase in adiponectin and phospho-AMPK levels, and a decrease in COX-2 level. In vitro, adiponectin significantly impaired the cell proliferation rate of MM cell lines. These effects partly involved induction of growth arrest and apoptosis to MM cells. MM cells expressed both adiponectin receptors 1 and 2 (AdipoR1 and -R2) at mRNA and proteins levels. These receptors were functional, because adiponectin activated AMPK. Adiponectin treatment also significantly down-regulated protein levels of COX-2 and its downstream prostaglandin E(2). Finally, inhibitory analysis of AdipoR1/R2 by small interfering RNA knockdown suggests that adiponectin enhances AMPK activity and impairs the cell proliferation rate of MM cells, mainly via AdipoR1. These findings suggest that the induction or supplementation of adiponectin is an important tactic for developing therapeutic strategies against MM.}, } @article {pmid22086453, year = {2011}, author = {Lange, J and Mastrangelo, G and Cegolon, L}, title = {Asbestos abatement workers versus asbestos workers: exposure and health-effects differ.}, journal = {International journal of occupational medicine and environmental health}, volume = {24}, number = {4}, pages = {418-9; author reply 420-1}, doi = {10.2478/s13382-011-0039-6}, pmid = {22086453}, issn = {1896-494X}, mesh = {Asbestos/*adverse effects ; Female ; Humans ; Lung Diseases/*etiology ; Male ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; Occupational Exposure/*standards ; Peritoneal Neoplasms/*etiology ; Pleural Neoplasms/*etiology ; }, } @article {pmid22084540, year = {2011}, author = {Abakay, A and Tanrikulu, AC and Kaplan, MA and Kucukoner, M and Abakay, O and Sen, H and Isikdogan, A and Senyigit, A}, title = {Clinical characteristics and treatment outcomes in 132 patients with malignant mesothelioma.}, journal = {Lung India : official organ of Indian Chest Society}, volume = {28}, number = {4}, pages = {267-271}, pmid = {22084540}, issn = {0974-598X}, abstract = {PURPOSE: Our objective is to scrutinize clinical, laboratory, radiological characteristics, treatment regimens, and treatment outcomes of malignant mesothelioma (MM) cases in our hospital.

MATERIALS AND METHODS: We investigated, retrospectively, the clinical characteristics and treatment outcomes of all 132 MM patients at Dicle University Hospital between January 2006 and April 2010.

RESULTS: A total of 82 (62.1%) patients were male, and 50 (37.9%) female. Median age was 56.0 years. Mean survival time was 9.6±6.9 months. Mean survival time of patients who had received best supportive care was 7.5 months, chemotherapy 10.4 months, and multimodality treatment regimen 12.6 months. Patients in the multimodality treatment group survived longer than did those in the other two groups (P=0.042). A total of 76 patients received chemotherapy, of whom 17 (22.3%) were administered Cisplatin/Carboplatin and Gemcitabine, 58 (76.4%) Cisplatin/Carboplatin and Pemetrexed, and one (1.3%) Cisplatin + Docetaxel. Complete and partial response to treatment in patients receiving Cisplatin/Carboplatin and Gemcitabine was found 47.1% and Cisplatin/Carboplatin and Pemetrexed was found 50.0% (P>0.05).

CONCLUSIONS: MM related to asbestos exposure is seen frequently in Turkey. Patients present with the typical clinical features of dyspnea, weight loss, and chest pain. Survival analysis shows that patients receiving multimodality treatment may be better.}, } @article {pmid22084509, year = {2011}, author = {Delgermaa, V and Takahashi, K and Park, EK and Le, GV and Hara, T and Sorahan, T}, title = {Global mesothelioma deaths reported to the World Health Organization between 1994 and 2008.}, journal = {Bulletin of the World Health Organization}, volume = {89}, number = {10}, pages = {716-24, 724A-724C}, pmid = {22084509}, issn = {1564-0604}, mesh = {Adult ; Aged ; Aged, 80 and over ; Databases, Factual ; Developing Countries ; Female ; *Global Health ; Humans ; Incidence ; Internationality ; Male ; Mesothelioma/epidemiology/*mortality ; Middle Aged ; Mortality/*trends ; Regression Analysis ; Risk Factors ; Time Factors ; *World Health Organization ; }, abstract = {OBJECTIVE: To carry out a descriptive analysis of mesothelioma deaths reported worldwide between 1994 and 2008.

METHODS: We extracted data on mesothelioma deaths reported to the World Health Organization mortality database since 1994, when the disease was first recorded. We also sought information from other English-language sources. Crude and age-adjusted mortality rates were calculated and mortality trends were assessed from the annual percentage change in the age-adjusted mortality rate.

FINDINGS: In total, 92,253 mesothelioma deaths were reported by 83 countries. Crude and age-adjusted mortality rates were 6.2 and 4.9 per million population, respectively. The age-adjusted mortality rate increased by 5.37% per year and consequently more than doubled during the study period. The mean age at death was 70 years and the male-to-female ratio was 3.6:1. The disease distribution by anatomical site was: pleura, 41.3%; peritoneum, 4.5%; pericardium, 0.3%; and unspecified sites, 43.1%. The geographical distribution of deaths was skewed towards high-income countries: the United States of America reported the highest number, while over 50% of all deaths occurred in Europe. In contrast, less than 12% occurred in middle- and low-income countries. The overall trend in the age-adjusted mortality rate was increasing in Europe and Japan but decreasing in the United States.

CONCLUSION: The number of mesothelioma deaths reported and the number of countries reporting deaths increased during the study period, probably due to better disease recognition and an increase in incidence. The different time trends observed between countries may be an early indication that the disease burden is slowly shifting towards those that have used asbestos more recently.}, } @article {pmid22084097, year = {2011}, author = {Nagai, H and Okazaki, Y and Chew, SH and Misawa, N and Yamashita, Y and Akatsuka, S and Ishihara, T and Yamashita, K and Yoshikawa, Y and Yasui, H and Jiang, L and Ohara, H and Takahashi, T and Ichihara, G and Kostarelos, K and Miyata, Y and Shinohara, H and Toyokuni, S}, title = {Diameter and rigidity of multiwalled carbon nanotubes are critical factors in mesothelial injury and carcinogenesis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {108}, number = {49}, pages = {E1330-8}, pmid = {22084097}, issn = {1091-6490}, mesh = {Animals ; Cell Line ; Cells, Cultured ; Comparative Genomic Hybridization ; Cyclin-Dependent Kinase Inhibitor p15/genetics ; Cyclin-Dependent Kinase Inhibitor p16/genetics ; Cytokines/genetics ; Epithelial Cells/*metabolism/ultrastructure ; Epithelium/injuries/ultrastructure ; Gene Deletion ; Gene Expression ; Humans ; Macrophages/metabolism ; Mesothelioma/etiology/*genetics/metabolism ; Microscopy, Electron, Scanning ; Microscopy, Electron, Transmission ; *Mutation ; Nanotubes, Carbon/*poisoning/ultrastructure ; Rats ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {Multiwalled carbon nanotubes (MWCNTs) have the potential for widespread applications in engineering and materials science. However, because of their needle-like shape and high durability, concerns have been raised that MWCNTs may induce asbestos-like pathogenicity. Although recent studies have demonstrated that MWCNTs induce various types of reactivities, the physicochemical features of MWCNTs that determine their cytotoxicity and carcinogenicity in mesothelial cells remain unclear. Here, we showed that the deleterious effects of nonfunctionalized MWCNTs on human mesothelial cells were associated with their diameter-dependent piercing of the cell membrane. Thin MWCNTs (diameter ∼ 50 nm) with high crystallinity showed mesothelial cell membrane piercing and cytotoxicity in vitro and subsequent inflammogenicity and mesotheliomagenicity in vivo. In contrast, thick (diameter ∼ 150 nm) or tangled (diameter ∼ 2-20 nm) MWCNTs were less toxic, inflammogenic, and carcinogenic. Thin and thick MWCNTs similarly affected macrophages. Mesotheliomas induced by MWCNTs shared homozygous deletion of Cdkn2a/2b tumor suppressor genes, similar to mesotheliomas induced by asbestos. Thus, we propose that different degrees of direct mesothelial injury by thin and thick MWCNTs are responsible for the extent of inflammogenicity and carcinogenicity. This work suggests that control of the diameter of MWCNTs could reduce the potential hazard to human health.}, } @article {pmid22083802, year = {2013}, author = {Sinon, SH and Rich, AM and Hussaini, HM and Yoon, HS and Firth, NA and Seymour, GJ}, title = {Metastases to the oral region from pleural mesothelioma: Clinicopathologic review.}, journal = {Head & neck}, volume = {35}, number = {4}, pages = {599-604}, doi = {10.1002/hed.21942}, pmid = {22083802}, issn = {1097-0347}, mesh = {Humans ; Mesothelioma/complications/*secondary ; Mouth Mucosa/*pathology ; Mouth Neoplasms/*secondary ; Neoplasm Metastasis ; Pleural Neoplasms/complications/*pathology ; }, abstract = {BACKGROUND: Malignant mesothelioma is a rare neoplasm that usually develops after exposure to asbestos and particularly involves the pleural cavity. It has a poor prognosis with aggressive local invasion and metastatic spread.

METHODS: The literature relating to malignant mesothelioma metastatic to the oral region was reviewed.

RESULTS: In all, 14 cases of malignant mesothelioma metastatic to the oral cavity were found. All were from pleural mesotheliomas, the tongue was the most common site of metastasis (8/14), and most metastases (9/13) were of the epithelioid type. The newly reported case is only the second report of a mesothelioma metastasizing to the buccal mucosa. It showed strong immunopositivity for keratin markers, vimentin, calretinin, and Wilms tumor product-1.

CONCLUSIONS: The incidence of mesothelioma is predicted to continue to increase for at least another decade. Clinicians and pathologists should be aware of this lesion and its propensity to metastasize to the oral cavity.}, } @article {pmid22076105, year = {2012}, author = {Kim, JS and Song, KS and Lee, JK and Choi, YC and Bang, IS and Kang, CS and Yu, IJ}, title = {Toxicogenomic comparison of multi-wall carbon nanotubes (MWCNTs) and asbestos.}, journal = {Archives of toxicology}, volume = {86}, number = {4}, pages = {553-562}, doi = {10.1007/s00204-011-0770-6}, pmid = {22076105}, issn = {1432-0738}, mesh = {Asbestos, Crocidolite/*toxicity ; Bronchi/drug effects ; Cell Line ; Cell Survival/drug effects ; Gene Expression Profiling ; Gene Expression Regulation/drug effects ; Humans ; Nanotubes, Carbon/*toxicity ; Oligonucleotide Array Sequence Analysis ; Respiratory Mucosa/*drug effects ; *Toxicogenetics ; }, abstract = {Carbon nanotubes (CNTs) have specific properties, including electrical and thermal conductivity, great strength, and rigidity, that allow them to be used in many fields. However, this increasing contact with humans and the environment is also raising health and safety concerns. Thus, research on the safety of CNTs has attracted much interest, including a comparison of the toxic effects of asbestos and carbon nanotubes, due to their physical similarity of a high aspect ratio (length/diameter). Nonetheless, there has not yet been a toxicogenomic comparison. Therefore, to examine toxicogenomic effects, the 50% growth inhibition (GI(50)) concentration was determined for multi-wall carbon nanotubes (MWCNTs) and asbestos (crocidolite) and found to be approximately 0.0135 and 0.066%, respectively, in the case of 24-h treatment of normal human bronchial epithelia (NHBE) cells. Using these GI(50) concentrations, NHBE cells were then treated with MWCNTs and asbestos for 6 and 24 h, followed by a DNA microarray analysis. Among 31,647 genes, 1,201 and 1,252 were up-regulated by both asbestos and MWCNTs after 6 and 24 h of exposure, respectively. Meanwhile, 1,977 and 1,542 genes were down-regulated by both asbestos and MWNCTs after 6 and 24 h of exposure, respectively. In particular, the asbestos and MWCNTs both induced an over twofold up- and down-regulated expression of 12 mesothelioma-related genes and 22 lung cancer-related genes when compared with the negative control. Plus, the genes induced by the MWCNT exposure were expressed in the brain, lungs, epithelium, liver, and colon.}, } @article {pmid22075480, year = {2012}, author = {Lacourt, A and Leffondré, K and Gramond, C and Ducamp, S and Rolland, P and Gilg Soit Ilg, A and Houot, M and Imbernon, E and Févotte, J and Goldberg, M and Brochard, P}, title = {Temporal patterns of occupational asbestos exposure and risk of pleural mesothelioma.}, journal = {The European respiratory journal}, volume = {39}, number = {6}, pages = {1304-1312}, doi = {10.1183/09031936.00005111}, pmid = {22075480}, issn = {1399-3003}, mesh = {Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Case-Control Studies ; France/epidemiology ; Humans ; Incidence ; Male ; Mesothelioma/*chemically induced/epidemiology ; Middle Aged ; Occupational Diseases/chemically induced/epidemiology ; Occupational Exposure/*statistics & numerical data ; Pleural Neoplasms/*chemically induced/epidemiology ; Risk ; }, abstract = {Asbestos is the primary cause of pleural mesothelioma (PM). The objective of this study was to elucidate the importance of different temporal patterns of occupational asbestos exposure on the risk of PM using case-control data in male subjects. Cases were selected from a French case-control study conducted in 1987-1993 and the French National Mesothelioma Surveillance Program in 1998-2006. Population controls were frequency matched to cases by year of birth. Occupational asbestos exposure was evaluated with a job-exposure matrix. The dose-response relationships were estimated using restricted cubic spline functions in logistic regression models. A total of 2,466 ever-asbestos-exposed males (1,041 cases and 1,425 controls) were used. After adjustment for intensity and total duration of occupational asbestos exposure, the risk of PM was lower for subjects first exposed after the age of 20 yrs and continued to increase until 30 yrs after cessation of exposure. The effect of total duration of exposure decreased when age at first exposure and time since last exposure increased. These results, based on a large population-based case-control study, underline the need to take into account the temporal pattern of exposure on risk assessment.}, } @article {pmid22073682, year = {2011}, author = {Lageard, G}, title = {[Causation in the court: the complex case of malignant mesothelioma].}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {33}, number = {3}, pages = {317-322}, pmid = {22073682}, issn = {1592-7830}, mesh = {Humans ; Italy ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; Occupational Health/*legislation & jurisprudence ; Pleural Neoplasms/*etiology ; }, abstract = {The aim of this paper is to carry out an analysis of the legal evolution in Italy of the assessment of causation i.e. cause and effect, in oncological diseases, a question taken into consideration by the High Court almost exclusively with reference to pleural mesothelioma. The most debated question when defining the causal association between asbestos exposure and mesothelioma is the possible role that any multiple potentially causative exposures could assume in the induction and development of the disease, and in particular the role of any asbestos exposure over the successive employment periods. Indeed, this is a subject on which, to date, no agreement has yet been reached in scientific doctrine: these divergences bear important practical significance from a legal point of view, since sustaining one thesis or another may constitute determining factors when ascertaining responsibility for individuals who, in the past, had decisional statuses in the workplace. Jurisprudence in the High Court took on an oscillating position on this question as from the early 2000s, which was divided into those who sustained the thesis of the relevance of any asbestos exposure over the successive employment periods and those who were of a different opinion, i.e. only the first exposure period has relevant causative effect. The point under discussion concerns, in particular, the adequacy of a probabilistic law only governing such a question. An important turning point was made in the year 2010 when two sentences were announced in the High Court, reiterating, in strict compliance with the principles affirmed by the United Sections in 2002, that a judge cannot, and must not, be satisfied with a general causation, but must rather reach a judgment on the basis of an individual causation. In particular, not only did the second of these two sentences recognise the multifactorial nature of mesothelioma, something which had almost always been denied in jurisprudence in the past, but it also established some very clear legal principles of law. Essentially, when ascertaining the causation, a judge should verify whether or not there is a sufficiently well established scientific law covering the question and whether such a law is universal or probabilistic. Should the latter be the case, then it is necessary to establish if the accelerating effect has been determined in the case in question, on the basis of the factual acquisitions. We must now wait for the concrete application of these principles by juridical bodies.}, } @article {pmid22065079, year = {2012}, author = {Carbone, M and Yang, H}, title = {Molecular pathways: targeting mechanisms of asbestos and erionite carcinogenesis in mesothelioma.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {18}, number = {3}, pages = {598-604}, pmid = {22065079}, issn = {1557-3265}, support = {P01 CA114047/CA/NCI NIH HHS/United States ; R01 CA160715/CA/NCI NIH HHS/United States ; R01CA160715-01/CA/NCI NIH HHS/United States ; R01 CA160715-01/CA/NCI NIH HHS/United States ; P01CA114047/CA/NCI NIH HHS/United States ; }, mesh = {Asbestos/*adverse effects ; Cell Transformation, Neoplastic/chemically induced/*genetics/pathology ; Humans ; Mesothelioma/*chemically induced/*genetics/pathology ; Zeolites/*adverse effects ; }, abstract = {Malignant mesothelioma is an aggressive malignancy related to asbestos and erionite exposure. AP-1 transcriptional activity and the NF-κB signaling pathway have been linked to mesothelial cell transformation and tumor progression. HGF and c-Met are highly expressed in mesotheliomas. Phosphoinositide 3-kinase, AKT, and the downstream mTOR are involved in cell growth and survival, and they are often found to be activated in mesothelioma. p16(INK4a) and p14(ARF) are frequently inactivated in human mesothelioma, and ∼50% of mesotheliomas contain the NF2 mutation. Molecular therapies aimed at interfering with these pathways have not improved the dismal prognosis of mesothelioma, except possibly for a small subset of patients who benefit from certain therapies. Recent studies have shown the importance of asbestos-induced inflammation in the initiation and growth of mesothelioma, and HMGB1 and Nalp3 inflammasome have been identified as key initiators of this process. Asbestos induces cell necrosis, causing the release of HMGB1, which in turn may activate Nalp3 inflammasome, a process that is enhanced by asbestos-induced production of reactive oxygen species. HMGB1 and Nalp3 induce proinflammatory responses and lead to interleukin-1β and TNF-α secretion and NF-κB activity, thereby promoting cell survival and tumor growth. Novel strategies that interfere with asbestos- and erionite-mediated inflammation might prevent or delay the onset of mesothelioma in high-risk cohorts, including genetically predisposed individuals, and/or inhibit tumor growth. The very recent discovery that germline BAP1 mutations cause a new cancer syndrome characterized by mesothelioma, uveal melanoma, and melanocytic tumors provides researchers with a novel target for prevention and early detection.}, } @article {pmid22048939, year = {2011}, author = {Baur, X and Schneider, J and Woitowitz, HJ}, title = {[Diagnosing and expertizing asbestos-induced occupational diseases].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {136}, number = {45}, pages = {2319-2324}, doi = {10.1055/s-0031-1292047}, pmid = {22048939}, issn = {1439-4413}, mesh = {Aged ; Asbestosis/*diagnosis/pathology ; Cooperative Behavior ; Disability Evaluation ; Eligibility Determination/legislation & jurisprudence ; Expert Testimony/*legislation & jurisprudence ; Germany ; Humans ; Interdisciplinary Communication ; Lung/pathology ; Lung Neoplasms/diagnosis/pathology ; Male ; Microscopy, Electron ; Pleura/pathology ; Pleural Neoplasms/diagnosis/pathology ; Practice Guidelines as Topic ; Pulmonary Disease, Chronic Obstructive/diagnosis/pathology ; Pulmonary Fibrosis/diagnosis/pathology ; Respiratory Function Tests ; Social Security/legislation & jurisprudence ; Societies, Medical ; Workers' Compensation/legislation & jurisprudence ; }, abstract = {Due to latency periods that can last for decades, asbestos-related diseases show 18 years after the enforcement of the prohibition of asbestos application in Germany their highest numbers. In the centre of attention are asbestos-induced pleural fibroses, mesotheliomas, asbestoses, lung and laryngeal cancer. Diagnosing and expertizing these diseases causes difficulties, is hitherto non-uniform and does frequently not correspond to the current medico-scientific expertise. This induced the German Respiratory Society as well as the German Society of Occupational and Environmental Medicine in cooperation with the German Society of Pathology, the German Radiology Society and the German Society of Otorhinolaryngology, Head and Cervical Surgery, to develop the above mentioned guideline during seven meetings moderated by AWMF. The required thorough diagnosis is based on the detailed recording of a qualified occupational history. Since the sole radiological and pathological-anatomical findings cannot sufficiently contribute to the causal relationship the occupational history recorded by a general physician and a specialist is of decisive importance. These physicians have to report suspected occupational diseases and to advise patients on social and medical questions. Frequently, problems occur if the recognition of an occupational disease is neglected due to a supposedly too low exposure or too few ferruginous bodies or low fibre concentrations in lung tissue. The new S2k directive summarizing the current medico-scientific knowledge is for this reason, for diagnoses and expert opinions as well as for the determination of a reduced capacity for work a very important source of information.}, } @article {pmid22036467, year = {2011}, author = {Gisquet, E and Chamming's, S and Pairon, JC and Gilg Soit Ilg, A and Imbernon, E and Goldberg, M}, title = {[The determinants of under-reporting occupational diseases. The case of mesothelioma].}, journal = {Revue d'epidemiologie et de sante publique}, volume = {59}, number = {6}, pages = {393-400}, doi = {10.1016/j.respe.2011.06.006}, pmid = {22036467}, issn = {0398-7620}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Lung Neoplasms/diagnosis/*epidemiology ; Male ; Mesothelioma/diagnosis/*epidemiology ; Occupational Diseases/diagnosis/*epidemiology ; Pleural Neoplasms/diagnosis/*epidemiology ; }, abstract = {BACKGROUND: Despite widespread press coverage of the harm caused by the asbestos, 40% of mesothelioma patients still do not file claims for compensation as an occupational disease. We aimed at studying elements that influence the administrative procedure of compensation, in particular social classes and instruction level.

METHODS: This was a statistical analysis of data from the French national survey program of mesothelioma designed to understand social determinants of reporting occupational illness. Data from a give administrative district were then submitted to a qualitative study using in-depth interviews of patients with suspected mesothelioma. Discourse analysis was then applied to the corpus of information collected. Content analysis grouped the data into themes.

RESULTS: The statistical analyses tended to show that the higher the educational level, the less often patients filed claims for their occupational disease. Manual workers asked for compensation for their disease more often than executives. The interviews conducted with suspected mesothelioma patients suggest several factors explaining these findings. The process of reporting an occupational disease is often initiated by the primary care physician who informs the patient about the possible link with a previous occupation, explains the procedure and motivate the patient whose main preoccupation is to fight against the illness, and less so to become recognized as a victim. In this context, the physician plays a fundamental role, independently of the patient's social status.

CONCLUSION: Those results throw new light on the complexity of the administrative procedure for reporting occupational diseases in France and highlights possible causes of underdeclaration reporting. Physician awarness of these causes might improve identification of links between occupation and disease and the transmission of adapted information to all concerned patients in order to fight more effectively against the disparities resulting from underreporting.}, } @article {pmid22033203, year = {2011}, author = {Costantino, C and Amodio, E and Costagliola, E and Curcurù, L and Ilardo, S and Trapani, E and Calamusa, G}, title = {[Asbestos-related diseases observed in Palermo (Italy) among workers exposed to asbestos].}, journal = {Igiene e sanita pubblica}, volume = {67}, number = {4}, pages = {455-466}, pmid = {22033203}, issn = {0019-1639}, mesh = {Adult ; Aged ; Algorithms ; *Asbestos/adverse effects ; Asbestosis/complications/*epidemiology/etiology ; Carcinoma/*epidemiology/etiology ; Female ; Humans ; Lung Neoplasms/*epidemiology/etiology ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; *Occupational Exposure/adverse effects ; Pleural Neoplasms/*epidemiology/etiology ; Retrospective Studies ; Risk Factors ; Sicily/epidemiology ; Smoking/adverse effects ; Time Factors ; }, abstract = {The aim of this study was to evaluate cases of asbestos-related diseases in workers exposed to asbestos in the province of Palermo (Italy) from 2005 to 2009. Data were collected from medical records and from reports from the Prevention and Safety in the Workplace Unit of the provincial health authorities of and between Palermo. Multinomial logistic regression showed a significant association between tobacco smoke and lung cancer and between starting work at an early stage and presence of asbestosis and pleural plaques. Results confirm that over eighteen years after the entry into force of Law 257/1992, which established the cessation of all activities related to asbestos, asbestos-related diseases continue being observed in clinical practice and represent a serious public health problem.}, } @article {pmid22025020, year = {2012}, author = {Fazzo, L and De Santis, M and Minelli, G and Bruno, C and Zona, A and Marinaccio, A and Conti, S and Comba, P}, title = {Pleural mesothelioma mortality and asbestos exposure mapping in Italy.}, journal = {American journal of industrial medicine}, volume = {55}, number = {1}, pages = {11-24}, doi = {10.1002/ajim.21015}, pmid = {22025020}, issn = {1097-0274}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Cluster Analysis ; Female ; Humans ; Incidence ; Italy/epidemiology ; Male ; Mesothelioma/*mortality ; Middle Aged ; Occupational Diseases/*mortality ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*mortality ; Poisson Distribution ; Risk ; }, abstract = {BACKGROUND: An epidemic of asbestos-related diseases is ongoing worldwide. Mortality from malignant pleural neoplasms in Italy was analyzed, to estimate the health impact of asbestos at national and local level.

METHODS: Mortality from ICD-9 code 163 was considered, in the time-window 1995-2002, using National Bureau of Statistics data. National and regional standardized rates and municipal Standardized Mortality Ratios (SMR) were calculated. Municipal clusters were identified by applying Spatial Scan Statistics procedure. Relative risks (RR) express the ratio of risk within the cluster to the risk outside the cluster.

RESULTS: The national standardized annual mortality rate was 1.9 per 100,000. Significant clusters corresponded to asbestos-cement industries (Casale Monferrato: RR = 11.63), shipyards (Monfalcone, RR = 7.43), oil refineries (Falconara, RR = 2.52), petrochemical industries (Priolo, RR = 3.81).

CONCLUSIONS: The present study confirms malignant pleural neoplasms mortality as a suitable indicator of asbestos exposure at geographic level. In addition to asbestos-cement industries and shipyards, other industrial settings are associated with pleural neoplasm mortality.}, } @article {pmid22024662, year = {2012}, author = {Malpica, A and Sant'Ambrogio, S and Deavers, MT and Silva, EG}, title = {Well-differentiated papillary mesothelioma of the female peritoneum: a clinicopathologic study of 26 cases.}, journal = {The American journal of surgical pathology}, volume = {36}, number = {1}, pages = {117-127}, doi = {10.1097/PAS.0b013e3182354a79}, pmid = {22024662}, issn = {1532-0979}, mesh = {Adult ; Aged ; Biomarkers, Tumor/analysis ; Calbindin 2 ; Female ; Humans ; Immunohistochemistry ; Keratin-5/analysis ; Keratin-6/analysis ; Mesothelioma/metabolism/*pathology ; Middle Aged ; Peritoneal Neoplasms/metabolism/*pathology ; Prognosis ; S100 Calcium Binding Protein G/analysis ; Young Adult ; }, abstract = {Well-differentiated papillary mesothelioma (WDPM) is an uncommon mesothelial tumor that occurs in the peritoneum of women over a wide age range. Although considered a tumor of uncertain malignant potential, information about its biological behavior is still limited. In this study, we present the clinicopathologic features of 26 cases of WDPM of the female peritoneum seen in our institution over a 20-year period (1990 to 2010). Clinical information and pathology material were reviewed in all cases. Patients ranged in age from 23 to 75 years (median, 47 y; mean, 48.6 y). There was no history of asbestos exposure in any of our cases. Ten patients had undergone surgery previously, and 6 had a history of endometriosis. In 24 patients, the WDPM was an incidental finding during surgery for a benign or malignant lesion. Only 2 patients presented with symptoms: 1 with an acute abdomen and the other with chronic pelvic pain. The former had developed a small hemoperitoneum because of bleeding of 1 of the lesions of WDPM, whereas the latter had a 2-cm WDPM involving the distal fallopian tube. The lesions were single or multiple (13 cases each) and ranged in size from 0.1 cm to 2 cm. The following sites were involved: abdominal or pelvic peritoneum not otherwise specified (10 cases), omentum (7 cases), cul-de-sac (6 cases), colonic serosa (4 cases), small bowel mesentery (2 cases), uterine serosa (2 cases), stomach serosa (1 case), large bowel mesentery (1 case), fallopian tube (1 case), ovary (1 case), and inguinal hernia (1 case). In all cases the lesions were excised. Microscopically, all of our cases had the typical features described for WDPM (ie, a papillary architecture that may be accompanied by glandular/tubular patterns, nests of cells and individual cells, bland mesothelial cells, absent or rare mitotic figures). The initial diagnosis in our cases was variable, including WDPM, mesothelial hyperplasia, malignant mesothelioma, serous tumor of low malignant potential of the peritoneum, papillary endosalpingiosis, and chronic xanthogranulomatous salpingiosis. Follow-up was obtained for 25 patients, and it ranged from 4 to 192 months (mean, 47.5 mo; median, 32 mo); 22 patients are alive with no evidence of WDPM after a follow-up that ranged from 5 to 144 months. One of these patients experienced recurrence of WDPM 46.5 months after initial diagnosis. In this patient, WDPM was an incidental finding during a total abdominal hysterectomy and bilateral salpingo-oophorectomy for serous cystadenofibroma. The recurrence was also an incidental finding during a colectomy for colonic adenocarcinoma. This patient is alive with no other recurrences 73 months after initial diagnosis and 36 months after diagnosis of the recurrence. Three patients died of other causes: pancreatic cancer at 4 months and 12 months and leukemia at 192 months. Recognition of the histologic features of WDPM and proper clinical correlation allow for the correct diagnosis of this entity. If necessary, immunohistochemical studies such as calretinin and keratin 5/6 facilitate the recognition of the mesothelial nature of this neoplasm. Although no patient died of disease in this series, follow-up of patients with this diagnosis is warranted on the basis of possible recurrences or misdiagnosis of an undersampled malignant mesothelioma.}, } @article {pmid22022760, year = {2011}, author = {Mensi, C and Bonzini, M and Macchione, M and Sieno, C and Riboldi, L and Pesatori, AC}, title = {Differences among peritoneal and pleural mesothelioma: data from the Lombardy Region Mesothelioma Register (Italy).}, journal = {La Medicina del lavoro}, volume = {102}, number = {5}, pages = {409-416}, pmid = {22022760}, issn = {0025-7818}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Environmental Exposure ; Female ; Humans ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Exposure ; Occupations ; Peritoneal Neoplasms/*epidemiology/etiology ; Pleural Neoplasms/*epidemiology/etiology ; Registries ; Retrospective Studies ; Risk Factors ; Time Factors ; }, abstract = {BACKGROUND: The relationship between asbestos exposure and peritoneal mesothelioma (PEM) is under investigation. Some authors suggest that the association could be weaker than that observed for pleural mesothelioma (PLM).

OBJECTIVE: To compare individual, clinical and exposure characteristics of peritoneal and pleural mesothelioma cases that occurred in the Lombardy Region (Italy).

METHODS: Cases were drawn from the regional mesothelioma registry (base population > 9 million). We selected all PEM cases diagnosed between 2000 and 2007 (N = 110) and all PLM cases that occurred between 2000 and 2001 (N = 515). Asbestos exposure data (occupational, environmental/familial, or both) were collected by a standardized and validated questionnaire administered to each case or case's relative. Based on available chest CT scans, we also investigated the concomitant presence of asbestosis and/or pleural plaques as markers of asbestos exposure.

RESULTS: PEM and PLM cases had similar proportions of occupational (around 60%) and environmental/familial (7%) asbestos exposure. The proportion of PEM subjects with co-existent occupational and environmental/familial exposures was, however, twice as high as PLM cases (6.1% vs 3.1%). Asbestosis and pleural plaques were more frequent in PEM than in PLM cases (7.7% and 20.9% vs 0.4% and 12.1%, respectively). No differences were detected for duration of exposure and latency among occupationally exposed cases.

CONCLUSION: Our findings from a population-based Registry suggest that high cumulative asbestos exposures are the main risk factors not only for pleural but also for peritoneal mesothelioma.}, } @article {pmid22022619, year = {2011}, author = {Creaney, J and Dick, IM and Yeoman, D and Wong, S and Robinson, BW}, title = {Auto-antibodies to β-F1-ATPase and vimentin in malignant mesothelioma.}, journal = {PloS one}, volume = {6}, number = {10}, pages = {e26515}, pmid = {22022619}, issn = {1932-6203}, mesh = {Aged ; Aged, 80 and over ; Amino Acid Sequence ; Autoantibodies/*blood/immunology ; Blotting, Western ; Cell Extracts ; Cell Line, Tumor ; Electrophoresis, Gel, Two-Dimensional ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Male ; Mesothelioma/*blood/enzymology/*immunology ; Middle Aged ; Mitochondrial Proton-Translocating ATPases/chemistry/*immunology ; Molecular Sequence Data ; Prognosis ; Protein Transport ; Sequence Alignment ; Survival Analysis ; Vimentin/chemistry/*immunology ; }, abstract = {Patients with Malignant Mesothelioma (MM) develop unidentified auto-antibodies to MM tumour antigens. This study was conducted to identify the targets of MM patient auto-antibodies in order to try to understand more of the anti-tumour response and to determine if these antibodies might be helpful for diagnosis or prognostication. Using MM patient sera in a Western immunoblott screening strategy, no common immunoreactive proteins were identified. The sera from one long-term survivor recognised a protein band of 50-60 kDa present in cell lysates from four of five MM cell lines tested. The immunoreactive proteins in this band were identified by 2D electrophoretic separation of a MM cell line protein lysate, followed by analysis of excised immunoreactive proteins on a MALDI TOF mass spectrometer and peptide mass fingerprinting. The immunoreactive proteins identified were vimentin (accession gi55977767) and the ATP synthase (F1-ATPase) beta chain (accession gi114549 and gi47606749). ELISA assays were developed for antibodies to these proteins. Neither vimentin (median and 95% CI 0.346; 0.32-0.468 for MM patients, 0.327; 0.308-0.428 for controls) nor ß-F1-ATPase (0.257; 0.221-0.453 for MM patients, 0.263; 0.22-0.35 for controls) showed significant differences in autoantibody levels between a group of MM patients and controls. Using a dichotomized antibody level (high, low) for these targets we demonstrated that vimentin antibody levels were not associated with survival. In contrast, high ß-F1-ATPase antibody levels were significantly associated with increased median survival (18 months) compared to low ß F1 ATPase antibody levels (9 months; p = 0.049). Immunohistochemical analysis on a MM tissue microarray showed cytoplasmic staining in 28 of 33 samples for vimentin and strong cytoplasmic staining in14 and weak in 16 samples for ß-F1-ATPase. Therefore antibodies to neither vimentin nor ß-F1-ATPase are useful for differential diagnosis of MM, however high antibody levels to ß-F1-ATPase may be associated with increased survival and this warrants further investigation.}, } @article {pmid22021116, year = {2013}, author = {Tresserra, F and Castella, M and Fabra, G and Angeles Martinez, M and Dominguez, M and Fernandez-Cid, C and Amalrich, MD and Ramos, C}, title = {Lymphohistiocytoid mesothelioma of the pleura: a case report with cytological findings.}, journal = {Diagnostic cytopathology}, volume = {41}, number = {6}, pages = {546-549}, doi = {10.1002/dc.21824}, pmid = {22021116}, issn = {1097-0339}, mesh = {Aged ; Female ; Histiocytes/pathology ; Humans ; Lymphocytes/pathology ; Mesothelioma/*diagnosis/pathology ; Pleura/*pathology ; Pleural Neoplasms/*diagnosis/pathology ; }, abstract = {Lymphohistiocytoid malignant mesothelioma is an infrequent variant of sarcomatoid mesothelioma representing approximately 0.5-3.3% of malignant mesotheliomas. It has been related to asbestos exposure. The tumor is characterized by a diffuse large histiocyte-like cells proliferation mixed with an inflammatory infiltrate of lymphocytes and plasma cells. Its cytological diagnosis is difficult. We present a case of a 67-year-old female with lymphohistiocytoid mesothelioma involving the left pleura. The cytological, histological, and immunohistochemical features are discussed.}, } @article {pmid22020536, year = {2012}, author = {Kao, SC and Armstrong, N and Condon, B and Griggs, K and McCaughan, B and Maltby, S and Wilson, A and Henderson, DW and Klebe, S}, title = {Aquaporin 1 is an independent prognostic factor in pleural malignant mesothelioma.}, journal = {Cancer}, volume = {118}, number = {11}, pages = {2952-2961}, doi = {10.1002/cncr.26497}, pmid = {22020536}, issn = {1097-0142}, mesh = {Adult ; Aged ; Aquaporin 1/*metabolism ; Biomarkers, Tumor/metabolism ; Female ; Humans ; Immunohistochemistry ; Male ; Mesothelioma/*diagnosis ; Microscopy, Immunoelectron ; Middle Aged ; Pleural Neoplasms/*diagnosis ; Prognosis ; }, abstract = {BACKGROUND: Malignant mesothelioma (MM) is an aggressive cancer of serosal membranes, mostly pleura. It is related to asbestos exposure and its incidence in most industrialized countries is projected to remain stable or to increase until 2020. Prognosis remains poor. Clinical prognostic scoring systems lack precision. No prognostic tissue markers are available. Aquaporin 1 (AQP1) is a cell membrane channel involved in water transport, cell motility, and proliferation. A blocker and an agonist are available.

METHODS: Two independent cohorts of MM were studied. Cohort 1 consisted of 80 consecutive patients who underwent radical surgery (extrapleural pneumonectomy [EPP]). Cohort 2 included 56 conservatively managed patients from another institution. Clinical information was obtained from files. Diagnoses were histologically verified. Immunohistochemical labeling for AQP1 was performed on tumor tissue and the percentage of positive cells was scored.

RESULTS: We demonstrated expression of AQP1 in normal and neoplastic mesothelium at the apical aspect of the cell, in keeping with a role in water transport. For both cohorts, expression of AQP1 by ≥50% of tumor cells was associated with significantly enhanced survival (9.4 months vs 30.4 months in EPP patients and 5 months vs 15 months in conservatively treated patients). This was independent of established prognostic factors, including histologic subtype, pathologic stage, sex, and age at time of diagnosis.

CONCLUSION: Expression of AQP1 correlated significantly with prognosis in MM, irrespective of treatment or established prognostic factors. Immunohistochemical labeling for AQP1 should be included in the routine histopathologic workup. An agonist or blocker may become useful for treatment.}, } @article {pmid22019695, year = {2012}, author = {Lee, YJ and Jeong, HY and Kim, YB and Lee, YJ and Won, SY and Shim, JH and Cho, MK and Nam, HS and Lee, SH}, title = {Reactive oxygen species and PI3K/Akt signaling play key roles in the induction of Nrf2-driven heme oxygenase-1 expression in sulforaphane-treated human mesothelioma MSTO-211H cells.}, journal = {Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association}, volume = {50}, number = {2}, pages = {116-123}, doi = {10.1016/j.fct.2011.10.035}, pmid = {22019695}, issn = {1873-6351}, mesh = {Cell Line, Tumor ; Cell Survival/drug effects ; Dose-Response Relationship, Drug ; Gene Expression Regulation, Enzymologic ; Heme Oxygenase-1/genetics/metabolism ; Humans ; Isothiocyanates ; Mesothelioma/*metabolism ; NF-E2-Related Factor 2/genetics/*metabolism ; Phosphatidylinositol 3-Kinases/*metabolism ; Phosphorylation ; Proto-Oncogene Proteins c-akt/genetics/*metabolism ; Reactive Oxygen Species/*metabolism ; Signal Transduction/*drug effects ; Sulfoxides ; Thiocyanates/administration & dosage/toxicity ; }, abstract = {The nuclear factor erythroid-derived 2 related factor 2 (Nrf2)/heme oxygenase (HO)-1 induction plays cytoprotective roles against oxidative injury, apoptosis, and anticancer therapy; however, little is known about its regulation in human mesothelioma MSTO-211H cells. In this study, we investigated Nrf2/HO-1 induction in response to sulforaphane and determined the signaling pathways involved in this process. Sulforaphane treatment decreased cell viability and triggered a rapid and transient increase in the intracellular ROS levels. Pretreatment with N-acetylcysteine (NAC) prevented sulforaphane-induced cytotoxicity. Erk1/2 was activated within 1h of sulforaphane addition, whereas Akt phosphorylation was suppressed until the first 8h, and was then maintained at an elevated level until 72h, displaying a biphasic regulatory feature. Nrf2 protein levels in both nuclear and whole cell lysates were increased after sulforaphane treatment and were decreased by pretreatment with NAC, actinomycin D and cycloheximide. Activation of the Nrf2/HO-1 system after sulforaphane treatment was suppressed by pretreatment with NAC or Ly294002, a PI3K inhibitor. Knockdown of Nrf2 with siRNA decreased cell viability and attenuated sulforaphane-induced HO-1 up-regulation. Overall, our results indicate that ROS generation and/or activation of PI3K/Akt signaling regulate cell survival and Nrf2-driven HO-1 expression in sulforaphane-treated MSTO-211H cells.}, } @article {pmid22017350, year = {2012}, author = {Sudo, H and Tsuji, AB and Sugyo, A and Ogawa, Y and Sagara, M and Saga, T}, title = {ZDHHC8 knockdown enhances radiosensitivity and suppresses tumor growth in a mesothelioma mouse model.}, journal = {Cancer science}, volume = {103}, number = {2}, pages = {203-209}, doi = {10.1111/j.1349-7006.2011.02126.x}, pmid = {22017350}, issn = {1349-7006}, mesh = {Acyltransferases/*genetics/metabolism ; Animals ; Apoptosis/radiation effects ; Cell Cycle Checkpoints ; Cell Line, Tumor ; Cell Proliferation ; Cell Survival/radiation effects ; Chromosomal Instability ; Disease Models, Animal ; Humans ; Membrane Proteins/*genetics/metabolism ; Mesothelioma/pathology/*radiotherapy ; Mice ; RNA Interference ; *RNA, Small Interfering/administration & dosage/pharmacology ; Radiation Tolerance ; Transfection ; Xenograft Model Antitumor Assays ; }, abstract = {Mesothelioma is an aggressive tumor caused by asbestos exposure, the incidence of which is predicted to increase globally. The prognosis of patients with mesothelioma undergoing conventional therapy is poor. Radiation therapy for mesothelioma is of limited use because of the intrinsic radioresistance of tumor cells compared with surrounding normal tissue. Thus, a novel molecular-targeted radiosensitizing agent that enhances the radiosensitivity of mesothelioma cells is required to improve the therapeutic efficacy of radiation therapy. ZDHHC8 knockdown reduces cell survival and induces an impaired G(2) /M checkpoint after X-irradiation in HEK293 cells. In the present study, we further analyzed the effect of the combination of ZDHHC8 knockdown and X-irradiation and assessed its therapeutic efficacy in mesothelioma models. SiRNA-induced ZDHHC8 knockdown in 211H and H2052 mesothelioma cells significantly reduced cell survival after X-irradiation. In 211H cells treated with ZDHHC8 siRNA and X-irradiation, the G(2) /M checkpoint was impaired and there was an increase in the number of cells with micronuclei, as well as apoptotic cells, in vitro. In 211H tumor-bearing mice, ZDHHC8 siRNA and X-irradiation significantly suppressed tumor growth, whereas ZDHHC8 siRNA alone did not. Immunohistochemical analysis showed decreased cell proliferation and induction of apoptosis in tumors treated with ZDHHC8 siRNA and X-irradiation, but not with ZDHHC8 siRNA alone. These results suggest that ZDHHC8 knockdown with X-irradiation induces chromosomal instability and apoptosis through the impaired G(2) /M checkpoint. In conclusion, the combination of ZDHHC8 siRNA and X-irradiation has the potential to improve the therapeutic efficacy of radiation therapy for malignant mesothelioma.}, } @article {pmid22011651, year = {2011}, author = {Kao, SC and Klebe, S and Henderson, DW and Reid, G and Chatfield, M and Armstrong, NJ and Yan, TD and Vardy, J and Clarke, S and van Zandwijk, N and McCaughan, B}, title = {Low calretinin expression and high neutrophil-to-lymphocyte ratio are poor prognostic factors in patients with malignant mesothelioma undergoing extrapleural pneumonectomy.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {6}, number = {11}, pages = {1923-1929}, doi = {10.1097/JTO.0b013e31822a3740}, pmid = {22011651}, issn = {1556-1380}, mesh = {Adult ; Aged ; Calbindin 2 ; Female ; Humans ; Immunoenzyme Techniques ; Kaplan-Meier Estimate ; Lymphocytes/*pathology ; Male ; Mesothelioma/*mortality/pathology/surgery ; Middle Aged ; Neoplasm Staging ; Neutrophils/*pathology ; Pleural Neoplasms/*mortality/pathology/surgery ; *Pneumonectomy ; Prognosis ; Retrospective Studies ; S100 Calcium Binding Protein G/*metabolism ; Survival Rate ; Young Adult ; }, abstract = {INTRODUCTION: Survival after extrapleural pneumonectomy (EPP) is variable in patients with malignant pleural mesothelioma (MPM), and there are no validated prognostic factors that could be used preoperatively. We investigated the calretinin and D2-40 expression and the neutrophil-to-lymphocyte ratio (NLR), an index of systemic inflammation as potential preoperative prognostic factors.

METHODS: Consecutive patients who underwent EPP were included in this retrospective study. Potential prognostic factors such as age, gender, histological subtype, baseline laboratory parameters including NLR, and immunohistochemical staining for calretinin and D2-40 were evaluated. Overall survival (OS) from the date of surgery was determined by the Kaplan-Meier method. The prognostic value of the variables was examined using Cox regression, and significant factors (p < 0.05) were entered into a multivariate model to determine their independent effect.

RESULTS: A total of 85 patients were included: median age 58 years; 80% men; 77% epithelial and 23% biphasic MPM. The median OS was 19.7 months. The following variables were predictive of longer OS: female gender (p = 0.02), epithelial subtype (p = 0.04), low NLR (p < 0.01), and high calretinin score (p < 0.001). In a multivariate analysis, only NLR ≥3 (hazard ratio 1.79; 95% confidence interval: 1.04-3.07; p = 0.04) and calretinin score ≤33 versus more than 67% (hazard ratio 4.72; 95% confidence interval: 1.97-11.32; p < 0.01) remained independent predictors. The addition of calretinin score increased the explained variation by 10.1%.

CONCLUSIONS: Both low calretinin expression and high NLR were independently associated with poor prognosis in patients with MPM undergoing EPP, and the calretinin score seemed to improve the accuracy of the prognostic model.}, } @article {pmid22007251, year = {2011}, author = {Kumagai-Takei, N and Maeda, M and Chen, Y and Matsuzaki, H and Lee, S and Nishimura, Y and Hiratsuka, J and Otsuki, T}, title = {Asbestos induces reduction of tumor immunity.}, journal = {Clinical & developmental immunology}, volume = {2011}, number = {}, pages = {481439}, pmid = {22007251}, issn = {1740-2530}, mesh = {Animals ; Antigens, Neoplasm/immunology ; Asbestos/*immunology/toxicity ; Carcinogens/toxicity ; DNA Damage/immunology ; Disease Models, Animal ; Early Detection of Cancer ; Gene Expression Regulation/immunology ; Humans ; Immunity ; Immunosuppression Therapy ; Lung Neoplasms/chemically induced/*diagnosis/genetics/*immunology ; Mesothelioma/chemically induced/diagnosis/genetics/*immunology ; Oxidative Stress/genetics/immunology ; }, abstract = {Asbestos-related cancers such as malignant mesothelioma and lung cancer are an important issue in the world. There are many conflicts concerning economical considerations and medical evidence for these cancers and much confusion regarding details of the pathological mechanisms of asbestos-induced cancers. For example, there is uncertainty concerning the degree of danger of the iron-absent chrysotile compared with iron-containing crocidolite and amosite. However, regarding bad prognosis of mesothelioma, medical approaches to ensure the recognition of the biological effects of asbestos and the pathological mechanisms of asbestos-induced carcinogenesis, as well as clinical trials to detect the early stage of mesothelioma, should result in better preventions and the cure of these malignancies. We have been investigating the immunological effects of asbestos in relation to the reduction of tumor immunity. In this paper, cellular and molecular approaches to clarify the immunological effects of asbestos are described, and all the findings indicate that the reduction of tumor immunity is caused by asbestos exposure and involvement in asbestos-induced cancers. These investigations may not only allow the clear recognition of the biological effects of asbestos, but also present a novel procedure for early detection of previous asbestos exposure and the presence of mesothelioma as well as the chemoprevention of asbestos-related cancers.}, } @article {pmid21988019, year = {2011}, author = {Price, R}, title = {The need for a regulatory response to diagnosis fraud in mesothelioma cases.}, journal = {Journal of law and medicine}, volume = {19}, number = {1}, pages = {196-200}, pmid = {21988019}, issn = {1320-159X}, mesh = {Asbestos/adverse effects ; Australia ; Compensation and Redress/*legislation & jurisprudence ; Fraud/*legislation & jurisprudence ; Humans ; Lung Neoplasms/*diagnosis ; Mesothelioma/*diagnosis ; }, abstract = {Australian courts and tribunals allow claimants with pleural plaques to "piggy back" compensation claims for mental health problems. This article contends that Australia is open to an era of diagnosis fraud by psychologists similar to that which has been experienced in the United States with radiologists. The courts will continue to reflect Australia's "compensation culture" unless legislation squarely addresses the compensability of pleural plaques and clarifies when, if at all, the courts should allow mental health claims for asymptomatic "marker" conditions such as pleural plaques.}, } @article {pmid21984916, year = {2011}, author = {Kanamori-Katayama, M and Kaiho, A and Ishizu, Y and Okamura-Oho, Y and Hino, O and Abe, M and Kishimoto, T and Sekihara, H and Nakamura, Y and Suzuki, H and Forrest, AR and Hayashizaki, Y}, title = {LRRN4 and UPK3B are markers of primary mesothelial cells.}, journal = {PloS one}, volume = {6}, number = {10}, pages = {e25391}, pmid = {21984916}, issn = {1932-6203}, mesh = {Animals ; Antibodies, Neoplasm/immunology ; Biomarkers/metabolism ; Cell Lineage ; Cells, Cultured ; Epithelial Cells/*metabolism/pathology ; Epithelium/metabolism ; Gene Expression Regulation ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Lung/cytology/metabolism ; Male ; Membrane Proteins/genetics/*metabolism ; Mesothelin ; Mesothelioma/genetics/immunology/pathology ; Mice ; Mice, Inbred C57BL ; Nerve Tissue Proteins/genetics/*metabolism ; Oligonucleotide Array Sequence Analysis ; Organ Specificity ; Reverse Transcriptase Polymerase Chain Reaction ; Uroplakin III/genetics/metabolism ; }, abstract = {BACKGROUND: Mesothelioma is a highly malignant tumor that is primarily caused by occupational or environmental exposure to asbestos fibers. Despite worldwide restrictions on asbestos usage, further cases are expected as diagnosis is typically 20-40 years after exposure. Once diagnosed there is a very poor prognosis with a median survival rate of 9 months. Considering this the development of early pre clinical diagnostic markers may help improve clinical outcomes.

METHODOLOGY: Microarray expression arrays on mesothelium and other tissues dissected from mice were used to identify candidate mesothelial lineage markers. Candidates were further tested by qRTPCR and in-situ hybridization across a mouse tissue panel. Two candidate biomarkers with the potential for secretion, uroplakin 3B (UPK3B), and leucine rich repeat neuronal 4 (LRRN4) and one commercialized mesothelioma marker, mesothelin (MSLN) were then chosen for validation across a panel of normal human primary cells, 16 established mesothelioma cell lines, 10 lung cancer lines, and a further set of 8 unrelated cancer cell lines.

CONCLUSIONS: Within the primary cell panel, LRRN4 was only detected in primary mesothelial cells, but MSLN and UPK3B were also detected in other cell types. MSLN was detected in bronchial epithelial cells and alveolar epithelial cells and UPK3B was detected in retinal pigment epithelial cells and urothelial cells. Testing the cell line panel, MSLN was detected in 15 of the 16 mesothelioma cells lines, whereas LRRN4 was only detected in 8 and UPK3B in 6. Interestingly MSLN levels appear to be upregulated in the mesothelioma lines compared to the primary mesothelial cells, while LRRN4 and UPK3B, are either lost or down-regulated. Despite the higher fraction of mesothelioma lines positive for MSLN, it was also detected at high levels in 2 lung cancer lines and 3 other unrelated cancer lines derived from papillotubular adenocarcinoma, signet ring carcinoma and transitional cell carcinoma.}, } @article {pmid21978187, year = {2011}, author = {Gkogkou, C and Samitas, K and Foteinou, M}, title = {Primary pleural epithelioid mesothelioma of clear cell type: a case report and review of current literature.}, journal = {Ultrastructural pathology}, volume = {35}, number = {6}, pages = {267-270}, doi = {10.3109/01913123.2011.606965}, pmid = {21978187}, issn = {1521-0758}, mesh = {Aged ; Asbestos/adverse effects ; Biomarkers, Tumor/analysis ; Biopsy ; Diagnosis, Differential ; Dyspnea/etiology ; Epithelioid Cells/chemistry/*pathology ; Humans ; Immunohistochemistry ; Male ; Mesothelioma/chemistry/etiology/*pathology/surgery ; Pleural Effusion, Malignant/etiology/pathology ; Pleural Neoplasms/chemistry/etiology/*pathology/surgery ; Predictive Value of Tests ; Thoracic Surgery, Video-Assisted ; }, abstract = {Primary pleural epithelioid mesothelioma with clear cell morphology is a particularly rare neoplasm, with only a few documented cases. Here, the authors report a case of a 76-year-old man, with a history of asbestos exposure, admitted for mild dyspnea. Radiologic examination revealed right pleural effusion and pleural thickening. Cytological examination of aspirated pleural samples was consistent with non-small cell carcinoma. Histological examination of the resected, via VATS, plural specimens was consistent with the diagnosis of clear cell epithelioid mesothelioma. The authors further analyze the main morphological and immunohistochemical features of clear cell epithelioid mesothelioma, emphasizing the algorithm for excluding other clear cell tumors metastatic to the pleura.}, } @article {pmid21955916, year = {2011}, author = {Yu, W and Chan-On, W and Teo, M and Ong, CK and Cutcutache, I and Allen, GE and Wong, B and Myint, SS and Lim, KH and Voorhoeve, PM and Rozen, S and Soo, KC and Tan, P and Teh, BT}, title = {First somatic mutation of E2F1 in a critical DNA binding residue discovered in well-differentiated papillary mesothelioma of the peritoneum.}, journal = {Genome biology}, volume = {12}, number = {9}, pages = {R96}, pmid = {21955916}, issn = {1474-760X}, mesh = {Adult ; Cell Proliferation ; Chromatin Immunoprecipitation ; DNA Mutational Analysis/methods ; E2F1 Transcription Factor/*genetics/metabolism ; Exome ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Mesothelioma/*genetics/pathology ; *Mutation ; Peritoneum/*pathology ; Plasmids/genetics/metabolism ; Promoter Regions, Genetic ; Protein Stability ; Transfection ; Tumor Cells, Cultured ; }, abstract = {BACKGROUND: Well differentiated papillary mesothelioma of the peritoneum (WDPMP) is a rare variant of epithelial mesothelioma of low malignancy potential, usually found in women with no history of asbestos exposure. In this study, we perform the first exome sequencing of WDPMP.

RESULTS: WDPMP exome sequencing reveals the first somatic mutation of E2F1, R166H, to be identified in human cancer. The location is in the evolutionarily conserved DNA binding domain and computationally predicted to be mutated in the critical contact point between E2F1 and its DNA target. We show that the R166H mutation abrogates E2F1's DNA binding ability and is associated with reduced activation of E2F1 downstream target genes. Mutant E2F1 proteins are also observed in higher quantities when compared with wild-type E2F1 protein levels and the mutant protein's resistance to degradation was found to be the cause of its accumulation within mutant over-expressing cells. Cells over-expressing wild-type E2F1 show decreased proliferation compared to mutant over-expressing cells, but cell proliferation rates of mutant over-expressing cells were comparable to cells over-expressing the empty vector.

CONCLUSIONS: The R166H mutation in E2F1 is shown to have a deleterious effect on its DNA binding ability as well as increasing its stability and subsequent accumulation in R166H mutant cells. Based on the results, two compatible theories can be formed: R166H mutation appears to allow for protein over-expression while minimizing the apoptotic consequence and the R166H mutation may behave similarly to SV40 large T antigen, inhibiting tumor suppressive functions of retinoblastoma protein 1.}, } @article {pmid21955238, year = {2011}, author = {Qi, F and Carbone, M and Yang, H and Gaudino, G}, title = {Simian virus 40 transformation, malignant mesothelioma and brain tumors.}, journal = {Expert review of respiratory medicine}, volume = {5}, number = {5}, pages = {683-697}, pmid = {21955238}, issn = {1747-6356}, support = {R01 CA106567-01A1/CA/NCI NIH HHS/United States ; R01 CA092657-01A1/CA/NCI NIH HHS/United States ; P01 CA114047/CA/NCI NIH HHS/United States ; R01 CA092657/CA/NCI NIH HHS/United States ; R01 CA106567/CA/NCI NIH HHS/United States ; P01 CA114047-01A1/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Brain Neoplasms/*virology ; *Cell Transformation, Viral ; DNA, Viral/isolation & purification ; Humans ; Mesothelioma/*virology ; Polyomavirus Infections/complications/*virology ; Risk Assessment ; Risk Factors ; Simian virus 40/genetics/*pathogenicity ; Tumor Virus Infections/complications/*virology ; }, abstract = {Simian virus 40 (SV40) is a DNA virus isolated in 1960 from contaminated polio vaccines, that induces mesotheliomas, lymphomas, brain and bone tumors, and sarcomas, including osteosarcomas, in hamsters. These same tumor types have been found to contain SV40 DNA and proteins in humans. Mesotheliomas and brain tumors are the two tumor types that have been most consistently associated with SV40, and the range of positivity has varied about from 6 to 60%, although a few reported 100% of positivity and a few reported 0%. It appears unlikely that SV40 infection alone is sufficient to cause human malignancy, as we did not observe an epidemic of cancers following the administration of SV40-contaminated vaccines. However, it seems possible that SV40 may act as a cofactor in the pathogenesis of some tumors. In vitro and animal experiments showing cocarcinogenicity between SV40 and asbestos support this hypothesis.}, } @article {pmid21952156, year = {2011}, author = {Menegozzo, S and Comba, P and Ferrante, D and De Santis, M and Gorini, G and Izzo, F and Magnani, C and Pirastu, R and Simonetti, A and Tùnesi, S and Menegozzo, M}, title = {Mortality study in an asbestos cement factory in Naples, Italy.}, journal = {Annali dell'Istituto superiore di sanita}, volume = {47}, number = {3}, pages = {296-304}, doi = {10.4415/ANN_11_03_10}, pmid = {21952156}, issn = {2384-8553}, mesh = {Adult ; Aged ; *Asbestos ; Asbestosis/*mortality ; *Carcinogens ; Cardiovascular Diseases/chemically induced/mortality ; Cohort Studies ; Construction Materials ; Female ; Humans ; Italy/epidemiology ; Lung Neoplasms/epidemiology/mortality ; Male ; Mesothelioma/epidemiology/mortality ; Middle Aged ; Occupational Diseases/chemically induced/*epidemiology/*mortality ; Occupational Exposure/analysis ; Peritoneal Neoplasms/epidemiology/mortality ; Pleural Neoplasms/epidemiology/mortality ; Pneumoconiosis/mortality ; Population ; Registries ; Young Adult ; }, abstract = {The objective of this paper is to investigate mortality among 1247 male asbestos-cement workers employed in an asbestos-cement plant located in Naples. The cohort included 1247 men hired between 1950 and 1986. The follow-up began on January 1st 1965. The vital status and causes of death were ascertained up to December 31 2005. Cause-specific mortality rates of the Campania Region population were used as reference. Relative risks were estimated using Standardized Mortality Ratios (SMRs), and the confidence intervals were calculated at a 95% level (95% CI). A significant increase in mortality was observed for respiratory disease (81 deaths; SMR = 187; 95% CI = 149- 233), particularly for pneumoconiosis (42 deaths; SMR = 13 313; 95% CI = 9595-17 996) of which 41 deaths for asbestosis (SMR = 43 385; 95% CI = 31 134-58 857), for pleural cancer (24 deaths; SMR = 2617; 95% CI = 1677-3893), for lung cancer (84 deaths; SMR=153; 95% CI = 122-189) and for peritoneal cancer (9 deaths; SMR = 1985; 95% CI = 908-3769). Non-significant increases were also observed for rectum cancer (6 deaths; SMR = 157; 95% CI = 58-342). In conclusion, consistently with other mortality studies on asbestos-cement workers performed in different countries, an increased mortality from asbestosis, lung cancer, pleural and peritoneal mesothelioma was detected in the present cohort.}, } @article {pmid21932006, year = {2012}, author = {Ishida, T and Alexandrov, M and Nishimura, T and Minakawa, K and Hirota, R and Sekiguchi, K and Kohyama, N and Kuroda, A}, title = {Evaluation of sensitivity of fluorescence-based asbestos detection by correlative microscopy.}, journal = {Journal of fluorescence}, volume = {22}, number = {1}, pages = {357-363}, pmid = {21932006}, issn = {1573-4994}, mesh = {Air/*analysis ; Asbestos, Serpentine/*analysis ; Microscopy, Fluorescence/*methods ; }, abstract = {Fluorescence microscopy (FM) has recently been applied to the detection of airborne asbestos fibers that can cause asbestosis, mesothelioma and lung cancer. In our previous studies, we discovered that the E. coli protein DksA specifically binds to the most commonly used type of asbestos, chrysotile. We also demonstrated that fluorescent-labeled DksA enabled far more specific and sensitive detection of airborne asbestos fibers than conventional phase contrast microscopy (PCM). However, the actual diameter of the thinnest asbestos fibers visualized under the FM platform was unclear, as their dimensions were below the resolution of optical microscopy. Here, we used correlative microscopy (scanning electron microscopy [SEM] in combination with FM) to measure the actual diameters of asbestos fibers visualized under the FM platform with fluorescent-labeled DksA as a probe. Our analysis revealed that FM offers sufficient sensitivity to detect chrysotile fibrils as thin as 30-35 nm. We therefore conclude that as an analytical method, FM has the potential to detect all countable asbestos fibers in air samples, thus approaching the sensitivity of SEM. By visualizing thin asbestos fibers at approximately tenfold lower magnifications, FM enables markedly more rapid counting of fibers than SEM. Thus, fluorescence microscopy represents an advanced analytical tool for asbestos detection and monitoring.}, } @article {pmid21930342, year = {2011}, author = {Toumpanakis, D and Theocharis, SE}, title = {DNA repair systems in malignant mesothelioma.}, journal = {Cancer letters}, volume = {312}, number = {2}, pages = {143-149}, doi = {10.1016/j.canlet.2011.08.021}, pmid = {21930342}, issn = {1872-7980}, mesh = {DNA Damage ; *DNA Repair ; Humans ; Mesothelioma/*genetics ; Polymorphism, Single Nucleotide ; }, abstract = {Malignant mesothelioma (MM) is an aggressive tumor of serosal surfaces with increasing incidence and poor prognosis. Asbestos exposure is the main cause of MM and asbestos-induced DNA damage is critical for MM pathogenesis. The present review summarizes the implications of DNA repair systems in MM development, focusing on gene expression alterations and single nucleotide polymorphisms of genes encoding for DNA repair enzymes. The involvement of DNA repair systems in MM improves understanding of MM pathogenesis and provides novel therapeutical targets.}, } @article {pmid21929381, year = {2011}, author = {Yang, M}, title = {A current global view of environmental and occupational cancers.}, journal = {Journal of environmental science and health. Part C, Environmental carcinogenesis & ecotoxicology reviews}, volume = {29}, number = {3}, pages = {223-249}, doi = {10.1080/10590501.2011.601848}, pmid = {21929381}, issn = {1532-4095}, mesh = {Biomarkers ; Carcinogens, Environmental/*toxicity ; Environmental Monitoring ; Humans ; Neoplasms/*chemically induced/prevention & control ; *Occupational Exposure ; }, abstract = {This review is focused on current information of avoidable environmental pollution and occupational exposure as causes of cancer. Approximately 2% to 8% of all cancers are thought to be due to occupation. In addition, occupational and environmental cancers have their own characteristics, e.g., specific chemicals and cancers, multiple factors, multiple causation and interaction, or latency period. Concerning carcinogens, asbestos/silica/wood dust, soot/polycyclic aromatic hydrocarbons [benzo(a) pyrene], heavy metals (arsenic, chromium, nickel), aromatic amines (4-aminobiphenyl, benzidine), organic solvents (benzene or vinyl chloride), radiation/radon, or indoor pollutants (formaldehyde, tobacco smoking) are mentioned with their specific cancers, e.g., lung, skin, and bladder cancers, mesothelioma or leukemia, and exposure routes, rubber or pigment manufacturing, textile, painting, insulation, mining, and so on. In addition, nanoparticles, electromagnetic waves, and climate changes are suspected as future carcinogenic sources. Moreover, the aspects of environmental and occupational cancers are quite different between developing and developed countries. The recent follow-up of occupational cancers in Nordic countries shows a good example for developed countries. On the other hand, newly industrializing countries face an increased burden of occupational and environmental cancers. Developing countries are particularly suffering from preventable cancers in mining, agriculture, or industries without proper implication of safety regulations. Therefore, industrialized countries are expected to educate and provide support for developing countries. In addition, citizens can encounter new environmental and occupational carcinogen nominators such as nanomaterials, electromagnetic wave, and climate exchanges. As their carcinogenicity or involvement in carcinogenesis is not clearly unknown, proper consideration for them should be taken into account. For these purposes, new technologies with a balance of environment and gene are required. Currently, various approaches with advanced technologies--genomics, exposomics, etc.--have accelerated development of new biomarkers for biological monitoring of occupational and environmental carcinogens. These advanced approaches are promising to improve quality of life and to prevent occupational and environmental cancers.}, } @article {pmid21928246, year = {2011}, author = {Dipalma, N and Luisi, V and Di Serio, F and Fontana, A and Maggiolini, P and Licchelli, B and Mera, E and Bisceglia, L and Galise, I and Loizzi, M and Pizzigallo, MA and Molinini, R and Vimercati, L}, title = {Biomarkers in malignant mesothelioma: diagnostic and prognostic role of soluble mesothelin-related peptide.}, journal = {The International journal of biological markers}, volume = {26}, number = {3}, pages = {160-165}, doi = {10.5301/JBM.2011.8614}, pmid = {21928246}, issn = {1724-6008}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; Female ; GPI-Linked Proteins/*metabolism ; Humans ; Lung Neoplasms/*diagnosis/pathology ; Male ; Mesothelin ; Mesothelioma/*diagnosis/pathology ; Mesothelioma, Malignant ; Middle Aged ; Peptides ; Prognosis ; }, abstract = {Soluble mesothelin-related peptide (SMRP) is a biomarker that has been proposed for differential diagnosis from pleural metastatic cancer, as well as prognosis and treatment monitoring of malignant pleural mesothelioma (MM). The aim of this study was to evaluate the role of SMRP in clinic management of MM. We assayed the SMRP concentrations in 354 subjects: 109 healthy volunteers with no history of exposure to asbestos, 26 patients with previous occupational asbestos exposure but who were free from pleural or parenchymal disease, 48 patients with asbestosis, 110 patients with pleural plaques, 25 patients with lung cancer, and 36 patients with MM. We also tested SMRP titers in 2 patients with MM at 5 different times of the disease, to evaluate the trend of the biomarker in the course of therapy. Our data confirm previous experiences with the use of SMRP as a diagnostic marker of MM. Low SMRP levels at diagnosis seem to have a positive prognostic significance.}, } @article {pmid21924581, year = {2012}, author = {Saleh, HZ and Fontaine, E and Elsayed, H}, title = {Malignant pleural mesothelioma presenting with a spontaneous hydropneumothorax: a report of 2 cases.}, journal = {Revista portuguesa de pneumologia}, volume = {18}, number = {2}, pages = {93-95}, doi = {10.1016/j.rppneu.2011.04.001}, pmid = {21924581}, issn = {2172-6825}, mesh = {Aged ; Humans ; Hydropneumothorax/*etiology ; Male ; Mesothelioma/*complications ; Pleural Neoplasms/*complications ; }, abstract = {Malignant pleural mesothelioma (MPM) originates in the mesothelial cells that line the pleural cavities. Most patients initially experience the insidious onset of chest pain or shortness of breath and have a history of asbestos exposure. It rarely presents as spontaneous pneumothorax. We report here two cases where malignant pleural mesothelioma presented with a spontaneous hydropneumothorax and was only discovered following surgery. We emphasise the need for a chest CT-scan preoperatively in older patients presenting with a secondary pneumo/hydropneumothorax.}, } @article {pmid21924516, year = {2012}, author = {Dragonieri, S and van der Schee, MP and Massaro, T and Schiavulli, N and Brinkman, P and Pinca, A and Carratú, P and Spanevello, A and Resta, O and Musti, M and Sterk, PJ}, title = {An electronic nose distinguishes exhaled breath of patients with Malignant Pleural Mesothelioma from controls.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {75}, number = {3}, pages = {326-331}, doi = {10.1016/j.lungcan.2011.08.009}, pmid = {21924516}, issn = {1872-8332}, mesh = {Aged ; Asbestos/toxicity ; Breath Tests/*methods ; Case-Control Studies ; Cross-Sectional Studies ; Female ; Humans ; Male ; Mesothelioma/*diagnosis ; Middle Aged ; Occupational Exposure ; Pleural Neoplasms/*diagnosis ; Reproducibility of Results ; Sensitivity and Specificity ; }, abstract = {BACKGROUND: Malignant Pleural Mesothelioma (MPM) is a tumour of the surface cells of the pleura that is highly aggressive and mainly caused by asbestos exposure. Electronic noses capture the spectrum of exhaled volatile organic compounds (VOCs) providing a composite biomarker profile (breathprint).

OBJECTIVE: We tested the hypothesis that an electronic nose can discriminate exhaled air of patients with MPM from subjects with a similar long-term professional exposure to asbestos without MPM and from healthy controls.

METHODS: 13 patients with a histology confirmed diagnosis of MPM (age 60.9±12.2 year), 13 subjects with certified, long-term professional asbestos exposure (age 67.2±9.8), and 13 healthy subjects without asbestos exposure (age 52.2±16.2) participated in a cross-sectional study. Exhaled breath was collected by a previously described method and sampled by an electronic nose (Cyranose 320). Breathprints were analyzed by canonical discriminant analysis on principal component reduction. Cross-validated accuracy (CVA) was calculated.

RESULTS: Breathprints from patients with MPM were separated from subjects with asbestos exposure (CVA: 80.8%, sensitivity 92.3%, specificity 85.7%). MPM was also distinguished from healthy controls (CVA: 84.6%). Repeated measurements confirmed these results.

CONCLUSIONS: Molecular pattern recognition of exhaled breath can correctly distinguish patients with MPM from subjects with similar occupational asbestos exposure without MPM and from healthy controls. This suggests that breathprints obtained by electronic nose have diagnostic potential for MPM.}, } @article {pmid21909417, year = {2011}, author = {Kirschner, MB and Kao, SC and Edelman, JJ and Armstrong, NJ and Vallely, MP and van Zandwijk, N and Reid, G}, title = {Haemolysis during sample preparation alters microRNA content of plasma.}, journal = {PloS one}, volume = {6}, number = {9}, pages = {e24145}, pmid = {21909417}, issn = {1932-6203}, mesh = {Biomarkers/blood ; Blood Specimen Collection/*methods ; Coronary Artery Disease/blood ; Erythrocytes/metabolism ; Hemoglobins/metabolism ; Hemolysis/*physiology ; Humans ; Mesothelioma/blood ; MicroRNAs/*blood ; }, abstract = {The presence of cell-free microRNAs (miRNAs) has been detected in a range of body fluids. The miRNA content of plasma/serum in particular has been proposed as a potential source of novel biomarkers for a number of diseases. Nevertheless, the quantification of miRNAs from plasma or serum is made difficult due to inefficient isolation and lack of consensus regarding the optimal reference miRNA. The effect of haemolysis on the quantification and normalisation of miRNAs in plasma has not been investigated in great detail. We found that levels of miR-16, a commonly used reference gene, showed little variation when measured in plasma samples from healthy volunteers or patients with malignant mesothelioma or coronary artery disease. Including samples with evidence of haemolysis led to variation in miR-16 levels and consequently decreased its ability to serve as a reference. The levels of miR-16 and miR-451, both present in significant levels in red blood cells, were proportional to the degree of haemolysis. Measurements of the level of these miRNAs in whole blood, plasma, red blood cells and peripheral blood mononuclear cells revealed that the miRNA content of red blood cells represents the major source of variation in miR-16 and miR-451 levels measured in plasma. Adding lysed red blood cells to non-haemolysed plasma allowed a cut-off level of free haemoglobin to be determined, below which miR-16 and miR-451 levels displayed little variation between individuals. In conclusion, increases in plasma miR-16 and miR-451 are caused by haemolysis. In the absence of haemolysis the levels of both miR-16 and miR-451 are sufficiently constant to serve as normalisers.}, } @article {pmid21905385, year = {2011}, author = {Dodson, RF and Hammar, SP and Poye, LW}, title = {Mesothelioma in an individual following exposure to crocidolite-containing gaskets as a teenager.}, journal = {International journal of occupational and environmental health}, volume = {17}, number = {3}, pages = {190-194}, doi = {10.1179/107735211799041995}, pmid = {21905385}, issn = {1077-3525}, mesh = {Air Pollutants, Occupational/*toxicity ; Asbestos, Crocidolite/*toxicity ; Dust ; Humans ; Lung Neoplasms/*chemically induced ; Male ; Mesothelioma/*chemically induced ; Middle Aged ; Occupational Exposure/*adverse effects ; Time Factors ; }, abstract = {Mesothelioma is considered a signal tumor for asbestos exposure and typically occurs decades after first exposure to asbestos. Tissue analysis often indicates past exposure to mixed types of asbestos. This report describes the case of a 58-year-old man who developed mesothelioma after reported exposure to crocidolite from asbestos-containing gaskets beginning at age 16 during three summers during high school and for approximately four hours per day during the last semester of his senior year. He had no further known exposure to asbestos. Analytical transmission electron microscopy analysis of digested tissue samples revealed elevated levels of crocidolite asbestos fibers and the presence of crocidolite cored ferruginous bodies. This case is unique in that it establishes that relatively short and/or intense exposures to crocidolite asbestos traumatically released from a previously classified Category 1 nonfriable asbestos-containing material (NESHAP) was confirmed via tissue burden analysis years following the historically defined exposures.}, } @article {pmid21895868, year = {2011}, author = {Nagai, H and Ishihara, T and Lee, WH and Ohara, H and Okazaki, Y and Okawa, K and Toyokuni, S}, title = {Asbestos surface provides a niche for oxidative modification.}, journal = {Cancer science}, volume = {102}, number = {12}, pages = {2118-2125}, pmid = {21895868}, issn = {1349-7006}, mesh = {8-Hydroxy-2'-Deoxyguanosine ; Aldehydes/metabolism ; Animals ; Asbestos, Amosite/*chemistry/metabolism/toxicity ; Asbestos, Crocidolite/*chemistry/toxicity ; Asbestos, Serpentine/*chemistry/metabolism ; Chromatin/metabolism ; Cytoskeleton/metabolism ; DNA/chemistry/metabolism ; *DNA Damage ; Deoxyguanosine/analogs & derivatives/biosynthesis ; Hemoglobins/metabolism ; Histones/metabolism ; Iron/metabolism ; Lung Neoplasms/etiology/pathology ; Mesothelioma/etiology/pathology ; Mice ; Oxidation-Reduction ; Proteins/chemistry/*metabolism ; RNA-Binding Proteins/metabolism ; Rats ; Ribosomal Proteins/metabolism ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Surface Properties ; }, abstract = {Asbestos is a potent carcinogen associated with increased risks of malignant mesothelioma and lung cancer in humans. Although the mechanism of carcinogenesis remains elusive, the physicochemical characteristics of asbestos play a role in the progression of asbestos-induced diseases. Among these characteristics, a high capacity to adsorb and accommodate biomolecules on its abundant surface area has been linked to cellular and genetic toxicity. Several previous studies identified asbestos-interacting proteins. Here, with the use of matrix-assisted laser desorption ionization-time of flight mass spectrometry, we systematically identified proteins from various lysates that adsorbed to the surface of commercially used asbestos and classified them into the following groups: chromatin/nucleotide/RNA-binding proteins, ribosomal proteins, cytoprotective proteins, cytoskeleton-associated proteins, histones and hemoglobin. The surfaces of crocidolite and amosite, two iron-rich types of asbestos, caused more protein scissions and oxidative modifications than that of chrysotile by in situ-generated 4-hydroxy-2-nonenal. In contrast, we confirmed the intense hemolytic activity of chrysotile and found that hemoglobin attached to chrysotile, but not silica, can work as a catalyst to induce oxidative DNA damage. This process generates 8-hydroxy-2'-deoxyguanosine and thus corroborates the involvement of iron in the carcinogenicity of chrysotile. This evidence demonstrates that all three types of asbestos adsorb DNA and specific proteins, providing a niche for oxidative modification via catalytic iron. Therefore, considering the affinity of asbestos for histones/DNA and the internalization of asbestos into mesothelial cells, our results suggest a novel hypothetical mechanism causing genetic alterations during asbestos-induced carcinogenesis.}, } @article {pmid21895596, year = {2011}, author = {Olsen, NJ and Franklin, PJ and Reid, A and de Klerk, NH and Threlfall, TJ and Shilkin, K and Musk, B}, title = {Increasing incidence of malignant mesothelioma after exposure to asbestos during home maintenance and renovation.}, journal = {The Medical journal of Australia}, volume = {195}, number = {5}, pages = {271-274}, doi = {10.5694/mja11.10125}, pmid = {21895596}, issn = {1326-5377}, mesh = {Aged ; Asbestos/*adverse effects ; Australia ; Building Codes/legislation & jurisprudence ; Causality ; Compensation and Redress/legislation & jurisprudence ; Construction Materials/*adverse effects ; Cross-Sectional Studies ; Female ; Forecasting ; Health Surveys ; *Housing ; Humans ; Incidence ; Liability, Legal ; *Maintenance/statistics & numerical data ; Male ; Mesothelioma/diagnosis/*epidemiology/prevention & control ; Middle Aged ; Occupational Exposure/statistics & numerical data ; Pleural Neoplasms/diagnosis/*epidemiology/prevention & control ; Registries/statistics & numerical data ; Sex Factors ; }, abstract = {OBJECTIVE: To determine trends in incidence of malignant mesothelioma (MM) caused by exposure to asbestos during home maintenance and renovation.

Using the Western Australian Mesothelioma Register, we reviewed all cases of MM diagnosed in WA from 1960 to the end of 2008, and determined the primary source of exposure to asbestos. Categories of exposure were collapsed into seven groups: asbestos miners and millers from Wittenoom; all other asbestos workers; residents from Wittenoom; home maintenance/renovators; other people exposed but not through their occupation; and people with unknown asbestos exposure; or no known asbestos exposure. Latency periods and age at diagnosis for each group were calculated and compared.

RESULTS: In WA, 1631 people (1408 men, 223 women) were diagnosed with MM between 1960 and 2008. Since 1981, there have been 87 cases (55 in men) of MM attributed to asbestos exposure during home maintenance and renovation, and an increasing trend in such cases, in both men and women. In the last 4 years of the study (2005-2008), home renovators accounted for 8.4% of all men and 35.7% of all women diagnosed with MM. After controlling for sex and both year and age at diagnosis, the latency period for people exposed to asbestos during home renovation was significantly shorter than that for all other exposure groups, but the shorter follow-up and difficulty recalling when exposure first occurred in this group may partly explain this.

CONCLUSIONS: MM after exposure to asbestos during home renovation is an increasing problem in WA, and these cases seem to have a shorter latency period than other types of exposure. MM cases related to renovation will probably continue to increase because of the many homes that have contained, and still contain, asbestos building products.}, } @article {pmid21895578, year = {2011}, author = {Gordon, JR and Leigh, J}, title = {Medicolegal aspects of the third wave of asbestos-related disease in Australia.}, journal = {The Medical journal of Australia}, volume = {195}, number = {5}, pages = {247-248}, doi = {10.5694/mja11.10899}, pmid = {21895578}, issn = {1326-5377}, mesh = {Asbestos/*adverse effects ; Construction Materials/*adverse effects ; Female ; *Housing ; Humans ; *Maintenance ; Male ; Mesothelioma/*epidemiology ; Pleural Neoplasms/*epidemiology ; }, } @article {pmid21895577, year = {2011}, author = {Katelaris, A}, title = {Renovation and renewal.}, journal = {The Medical journal of Australia}, volume = {195}, number = {5}, pages = {245}, doi = {10.5694/mja11.c0905}, pmid = {21895577}, issn = {1326-5377}, mesh = {Asbestos/*adverse effects ; Compensation and Redress/*legislation & jurisprudence ; Construction Materials/*adverse effects ; Housing/*legislation & jurisprudence ; Humans ; *Liability, Legal ; Mesothelioma/*epidemiology ; Pleural Neoplasms/*epidemiology ; }, } @article {pmid21890228, year = {2012}, author = {Kuribayashi, K and Voss, S and Nishiuma, S and Arakawa, K and Nogi, Y and Mikami, K and Kudoh, S}, title = {Safety and effectiveness of pemetrexed in patients with malignant pleural mesothelioma based on all-case drug-registry study.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {75}, number = {3}, pages = {353-359}, doi = {10.1016/j.lungcan.2011.08.002}, pmid = {21890228}, issn = {1872-8332}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use ; Cisplatin/administration & dosage ; Female ; Glutamates/administration & dosage/*adverse effects ; Guanine/administration & dosage/adverse effects/*analogs & derivatives ; Humans ; Japan ; Male ; Mesothelioma/*drug therapy/mortality ; Middle Aged ; Pemetrexed ; Pleural Neoplasms/*drug therapy/mortality ; Survival Rate ; Treatment Outcome ; }, abstract = {BACKGROUND: Pemetrexed in combination with cisplatin (Pem/Cis) is the only approved chemotherapeutic regimen for malignant pleural mesothelioma (MPM). At the time of launch, limited safety information was available. The purpose of this postmarketing all-case registry study was to investigate the safety and effectiveness of pemetrexed in patients with MPM.

METHODS: From January 2007 to May 2008, MPM patients to be treated with pemetrexed in Japan were registered to this study to monitor its safety and effectiveness. Supply of pemetrexed was restricted to institutions with experienced medical oncologists based on predetermined criteria.

RESULTS: Of 953 patients registered, data from 903 patients were eligible for analysis. Most patients were male, with median age of 65 years and 68.5% had a history of asbestos exposure. More than 90% of patients received the first cycle of Pem/Cis treatment; median number of treatment cycles was 4.0. Treatment-associated death was reported in 0.8% of patients. The incidence of Interstitial lung disease (ILD) associated with Pem/Cis during the observation period was 0.9%. The frequency of ILD in patients with pre-existing asbestosis was higher than that in patients without it. For tumor response, the overall response rate was 25.0% (95% confidence interval (CI): 22.2-28.0%). The six-month survival rate estimated by the Kaplan-Meier method was 75.9%.

CONCLUSIONS: This large scale all case registry study appeared to have enrolled a major portion of Japanese MPM patients. Treatment with pemetrexed was generally well tolerated and showed safety and effectiveness comparable to prior clinical trials.}, } @article {pmid21886962, year = {2011}, author = {Nicolini, A and Perazzo, A and Lanata, S}, title = {Desmoplastic malignant mesothelioma of the pericardium: Description of a case and review of the literature.}, journal = {Lung India : official organ of Indian Chest Society}, volume = {28}, number = {3}, pages = {219-221}, pmid = {21886962}, issn = {0974-598X}, abstract = {Desmoplastic mesothelioma (DMM) is a rare and highly lethal subtype of diffuse malignant mesothelioma and is often difficult to distinguish from reactive pleural fibrosis. The term "desmoplastic" refers to the growth of fibrous or connective tissue. We report the clinical, radiological, and pathological features of a primary DMM of the pericardium and a short review of the literature. A 72-year-old man was admitted presenting shortness of breath, cough, and asthenia. Computed tomography scan showed thickenings and effusions both in the pleura and in the pericardium. Histopathological diagnosis was performed by surgical pericardial biopsy and confirmed by autopsy. The patient had a history of asbestos exposure. Primary mesothelioma of the pericardium is a rare tumor occurring in the fourth to seventh decades with nonspecific symptoms and a rapid clinical course. The diagnosis is difficult and often needing a surgical pericardial biopsy. The prognosis is poor although newer antiblastic drugs seem to prolong survival times.}, } @article {pmid21876457, year = {2011}, author = {Lang-Lazdunski, L and Bille, A and Belcher, E and Cane, P and Landau, D and Steele, J and Taylor, H and Spicer, J}, title = {Pleurectomy/decortication, hyperthermic pleural lavage with povidone-iodine followed by adjuvant chemotherapy in patients with malignant pleural mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {6}, number = {10}, pages = {1746-1752}, doi = {10.1097/JTO.0b013e3182288af9}, pmid = {21876457}, issn = {1556-1380}, mesh = {Aged ; Anti-Infective Agents, Local/*therapeutic use ; Chemotherapy, Adjuvant ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; *Hyperthermia, Induced ; Male ; Mesothelioma/*therapy ; Middle Aged ; Neoplasm Staging ; Pleural Neoplasms/*therapy ; Pneumonectomy ; Positron-Emission Tomography ; Povidone-Iodine/*therapeutic use ; Prospective Studies ; Radiotherapy, Adjuvant ; Survival Rate ; Treatment Outcome ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma is a fatal neoplasm related to asbestos exposure. We investigated the effects of pleurectomy/decortication (P/D), hyperthermic pleural lavage with povidone-iodine and adjuvant chemotherapy in patients with malignant pleural mesothelioma.

PATIENTS AND METHODS: Observational prospective study of patients referred for multimodality therapy and operated on at our institution between October 2004 and May 2010. Thirty-six selected patients underwent P/D and hyperthermic pleural lavage, prophylactic radiotherapy, and adjuvant chemotherapy. All patients were reviewed at 4 weeks and then 6 monthly in the outpatient clinic, with positron-emission tomography-computed tomography. Second-line treatments were administered when appropriate.

RESULTS: Thirty-day mortality was nil. Nine patients experienced postoperative complications: persistent air leak (n = 5, 13.9%), chylothorax requiring surgical intervention (n = 4, 11%), and adult respiratory distress syndrome (n = 1, 3.9%). Fourteen of 36 patients were alive at last follow-up (median follow-up: 33 months, range: 12-63 months). Ten patients were alive with no evidence of disease recurrence, four patients were alive with disease recurrence, and 22 patients had died of disease progression. Overall median survival (Kaplan-Meier) was 24 months (95% confidence interval: 18.5-29.4 months). One-year survival was 91.7%, and 2-year survival was 61%. Patients undergoing complete macroscopical resection (R0-R1) had a significantly better survival than those undergoing an incomplete macroscopical resection (R2) (median overall survival: 32 months versus 18.9 months, p = 0.012).

CONCLUSION: In our experience, P/D combined with hyperthermic pleural lavage with povidone-iodine and adjuvant chemotherapy is a well-tolerated multimodality treatment associated with low morbidity and mortality. This multimodality treatment compares favorably with classical trimodality regimens involving chemotherapy, extrapleural pneumonectomy, and adjuvant radiotherapy, in our experience. Study limitations include small sample size, nonrandomization, and patient selection bias.}, } @article {pmid21874000, year = {2011}, author = {Testa, JR and Cheung, M and Pei, J and Below, JE and Tan, Y and Sementino, E and Cox, NJ and Dogan, AU and Pass, HI and Trusa, S and Hesdorffer, M and Nasu, M and Powers, A and Rivera, Z and Comertpay, S and Tanji, M and Gaudino, G and Yang, H and Carbone, M}, title = {Germline BAP1 mutations predispose to malignant mesothelioma.}, journal = {Nature genetics}, volume = {43}, number = {10}, pages = {1022-1025}, pmid = {21874000}, issn = {1546-1718}, support = {P30CA-06927/CA/NCI NIH HHS/United States ; P30CA-71789/CA/NCI NIH HHS/United States ; P01 CA114047/CA/NCI NIH HHS/United States ; P01CA-114047/CA/NCI NIH HHS/United States ; P30 CA006927-49/CA/NCI NIH HHS/United States ; P01 CA114047-05/CA/NCI NIH HHS/United States ; P30 CA071789-12S9/CA/NCI NIH HHS/United States ; P30 CA071789/CA/NCI NIH HHS/United States ; P30 CA006927/CA/NCI NIH HHS/United States ; }, mesh = {Asbestos/toxicity ; Environmental Exposure ; Female ; Genetic Linkage ; Genetic Predisposition to Disease ; *Germ-Line Mutation ; Humans ; Male ; Melanoma/genetics ; Mesothelioma/*genetics/pathology ; Pedigree ; Pleural Neoplasms/*genetics/pathology ; Risk Factors ; Tumor Suppressor Proteins/*genetics/metabolism ; Ubiquitin Thiolesterase/*genetics/metabolism ; Uveal Neoplasms/genetics ; }, abstract = {Because only a small fraction of asbestos-exposed individuals develop malignant mesothelioma, and because mesothelioma clustering is observed in some families, we searched for genetic predisposing factors. We discovered germline mutations in the gene encoding BRCA1 associated protein-1 (BAP1) in two families with a high incidence of mesothelioma, and we observed somatic alterations affecting BAP1 in familial mesotheliomas, indicating biallelic inactivation. In addition to mesothelioma, some BAP1 mutation carriers developed uveal melanoma. We also found germline BAP1 mutations in 2 of 26 sporadic mesotheliomas; both individuals with mutant BAP1 were previously diagnosed with uveal melanoma. We also observed somatic truncating BAP1 mutations and aberrant BAP1 expression in sporadic mesotheliomas without germline mutations. These results identify a BAP1-related cancer syndrome that is characterized by mesothelioma and uveal melanoma. We hypothesize that other cancers may also be involved and that mesothelioma predominates upon asbestos exposure. These findings will help to identify individuals at high risk of mesothelioma who could be targeted for early intervention.}, } @article {pmid21861135, year = {2011}, author = {Hmeljak, J and Erčulj, N and Dolžan, V and Kern, I and Cör, A}, title = {BIRC5 promoter SNPs do not affect nuclear survivin expression and survival of malignant pleural mesothelioma patients.}, journal = {Journal of cancer research and clinical oncology}, volume = {137}, number = {11}, pages = {1641-1651}, pmid = {21861135}, issn = {1432-1335}, mesh = {Cell Nucleus/*metabolism ; Genotype ; Haplotypes ; Humans ; Inhibitor of Apoptosis Proteins/*genetics/metabolism ; Mesothelioma/*genetics/metabolism/pathology ; Pleural Neoplasms/*genetics/metabolism/pathology ; *Polymorphism, Single Nucleotide ; *Promoter Regions, Genetic ; Survival Analysis ; Survivin ; }, abstract = {PURPOSE: Malignant pleural mesothelioma is an incurable, asbestos-associated cancer. Its incidence is rapidly increasing and survival remains short. Apoptosis deregulation is an important feature of cancer and survivin, a member of the inhibitor-of-apoptosis-protein family encoded by the BIRC5 gene, has been suggested to have a role in the development and progression of several cancers. Genetic variability, in particular single nucleotide polymorphisms in the BIRC5 promoter, may affect the protein's expression levels. The aim of our study was to elucidate the effects of BIRC5 promoter single nucleotide polymorphisms on survivin expression, patient survival and age at diagnosis in malignant pleural mesothelioma.

METHODS: Archival mesothelioma samples from 101 Slovenian patients were immunohistochemically analysed for survivin expression. DNA was extracted from tumour samples and genotyped for three BIRC5 promoter single nucleotide polymorphisms (-31G > C, -241C > T and -625G > C). Genotypes were associated with nuclear survivin expression. Nuclear survivin expression, genotypes, haplotypes, histological type, gender and asbestos exposure were included in univariate Cox survival analyses.

RESULTS: Survivin expression was detected in both tumour cell nuclei and cytoplasms in all analysed samples. No association between BIRC5 promoter polymorphism genotypes or haplotypes and nuclear survivin expression was found. Polymorphism -241C > T affected patients' age at diagnosis. Survival analysis confirmed that younger age at diagnosis and epitheloid histological type improved survival, but no significant effects of nuclear survivin expression or genotype/haplotype on overall survival were observed.

CONCLUSION: Our findings indicate no relationship between BIRC5 genotypes and survivin expression or overall survival in mesothelioma patients. We observed that BIRC5 -241C > T polymorphism had a significant effect on patient age at diagnosis.}, } @article {pmid21858171, year = {2011}, author = {Baldi, A and Piccolo, MT and Boccellino, MR and Donizetti, A and Cardillo, I and La Porta, R and Quagliuolo, L and Spugnini, EP and Cordero, F and Citro, G and Menegozzo, M and Calogero, RA and Crispi, S}, title = {Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma.}, journal = {PloS one}, volume = {6}, number = {8}, pages = {e23569}, pmid = {21858171}, issn = {1932-6203}, mesh = {Antineoplastic Agents/administration & dosage/pharmacology ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Apoptosis/*drug effects ; Blotting, Western ; Cell Line, Tumor ; Cisplatin/administration & dosage/*pharmacology ; Cyclin-Dependent Kinase Inhibitor Proteins/genetics/metabolism ; Cyclin-Dependent Kinase Inhibitor p21/*genetics/metabolism ; Cyclooxygenase Inhibitors/administration & dosage/pharmacology ; Drug Synergism ; Dual-Specificity Phosphatases/genetics/metabolism ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Mesothelioma/drug therapy/*genetics/pathology ; Oligonucleotide Array Sequence Analysis ; Piroxicam/administration & dosage/*pharmacology ; RNA Interference ; Reverse Transcriptase Polymerase Chain Reaction ; Time Factors ; }, abstract = {BACKGROUND: Malignant mesothelioma (MM) is a rare, highly aggressive tumor, associated to asbestos exposure. To date no chemotherapy regimen for MM has proven to be definitively curative, and new therapies for MM treatment need to be developed. We have previously shown in vivo that piroxicam/cisplatin combined treatment in MM, specifically acts on cell cycle regulation triggering apoptosis, with survival increase.

We analyzed, at molecular level, the apoptotic increase caused by piroxicam/cisplatin treatment in MM cell lines. By means of genome wide analyses, we analyzed transcriptional gene deregulation both after the single piroxicam or cisplatin and the combined treatment. Here we show that apoptotic increase following combined treatment is mediated by p21, since apoptotic increase in piroxicam/cisplatin combined treatment is abolished upon p21 silencing.

CONCLUSIONS/SIGNIFICANCE: Piroxicam/cisplatin combined treatment determines an apoptosis increase in MM cells, which is dependent on the p21 expression. The results provided suggest that piroxicam/cisplatin combination might be tested in clinical settings in tumor specimens that express p21.}, } @article {pmid21834915, year = {2011}, author = {Allen, RK and Cramond, T and Lennon, D and Waterhouse, M}, title = {A retrospective study of chest pain in benign asbestos pleural disease.}, journal = {Pain medicine (Malden, Mass.)}, volume = {12}, number = {9}, pages = {1303-1308}, doi = {10.1111/j.1526-4637.2011.01209.x}, pmid = {21834915}, issn = {1526-4637}, mesh = {Aged ; Asbestosis/diagnostic imaging/*epidemiology/pathology ; Chest Pain/diagnosis/diagnostic imaging/*epidemiology ; Cohort Studies ; Comorbidity/trends ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Pleural Diseases/diagnostic imaging/*epidemiology/pathology ; Radiography ; Retrospective Studies ; }, abstract = {PURPOSE: The aims of this review were to ascertain the incidence of asbestos-related chest pain at presentation in two groups of patients referred with asbestos diseases and the demographics, comorbidities, and chest computed tomography findings associated with chest pain.

METHODS: Medical charts of patients presenting 1995-2008, audited for quality assurance, were chosen at random by data managers. Patients with mesothelioma, lung cancer, and angina were excluded. Rigorous attempts had been taken by the authors to exclude other causes of chest pain.

RESULTS: There were 167 patients who were medicolegal referrals (Group 1) and 115 clinical referrals (Group 2). Although the patients in Group 1 had more severe disease generally than Group 2, the proportion with pain was not significantly different (45.5% and 55.7%, mean duration 4.8 years, range 1-22 years). Group 1 had more severe disease as a rule. However, the proportion with pain in Groups 1 and 2, respectively, was as follows: diffuse pleural thickening (50.8% and 67.6%, P=0.072), pleural plaques (47.0% and 59.7%, P=0.076), folded atelectasis (70.6% and 83.3%, P=1.000), and asbestosis (43.6% and 53.3%, P=0.346). Of all those with folded atelectasis, 73.9% had pain.

CONCLUSION: Chest pain appears to be much more common in patients with benign asbestos diseases than is currently recognized, particularly in those with folded atelectasis and is not restricted to litigants. Improved recognition of this entity is needed along with practical management guidelines for the general practitioner. Further studies are envisaged by the authors.}, } @article {pmid21831850, year = {2011}, author = {Teta, MJ}, title = {Mesothelioma in a connecticut friction plant: the need for transparency and exposure information in attribution of risk.}, journal = {The Annals of occupational hygiene}, volume = {55}, number = {7}, pages = {817-9; author reply 820-2}, doi = {10.1093/annhyg/mer049}, pmid = {21831850}, issn = {1475-3162}, mesh = {Air Pollutants, Occupational/*analysis ; Asbestos, Serpentine/*analysis ; Female ; Humans ; Male ; *Manufactured Materials ; Mesothelioma/*mortality ; Occupational Exposure/*adverse effects ; }, } @article {pmid21821492, year = {2011}, author = {Lianes, P and Remon, J and Bover, I and Isla, D}, title = {SEOM guidelines for the treatment of malignant pleural mesothelioma.}, journal = {Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico}, volume = {13}, number = {8}, pages = {569-573}, pmid = {21821492}, issn = {1699-3055}, mesh = {Algorithms ; Antineoplastic Agents/pharmacology ; Female ; Humans ; Male ; Medical Oncology/*methods ; Mesothelioma/*therapy ; Neoplasm Staging ; Pleural Neoplasms/*therapy ; Radiotherapy/methods ; Societies, Medical ; Treatment Outcome ; }, abstract = {Mesothelioma is a rare malignant tumour. Asbestos is the principal aetiological agent of malignant pleural mesothelioma (MPM) (≈80% of cases). The incidence of MPM is still increasing and will peak within the next 10 years. There are three main histological types of MPM: epithelial (≈60%), sarcomatous and mixed. There is no standard approach for patients with MPM. Surgery (radical extra-pleural pneumonectomy or pleurectomy/decortication) may be part of the initial treatment for carefully selected patients, generally combined with neoadjuvant or adjuvant chemotherapy and/or adjuvant radiotherapy, and should only be performed by experienced thoracic surgeons as part of a multidisciplinary team. Radiotherapy could be used as prophylaxis to reduce the incidence of recurrence at sites of diagnoses or therapeutic instrument insertion, in a multimodal treatment to improve locoregional control and to palliate symptoms. Based on the better compliance of neoadjuvant chemotherapy, lower rate of surgical morbidity and the possibility to select the optimal patients to be submitted to surgery, a neoadjuvant strategy is a better option than adjuvant chemotherapy, although there is no standard optimal sequence and types of treatment for multimodal therapy. In patients with no resectable disease, chemotherapy is the best option with platinum and pemetrexed or raltitrexed. At this time there is no widely approved salvage therapy.}, } @article {pmid21820631, year = {2011}, author = {Kanarek, MS}, title = {Mesothelioma from chrysotile asbestos: update.}, journal = {Annals of epidemiology}, volume = {21}, number = {9}, pages = {688-697}, doi = {10.1016/j.annepidem.2011.05.010}, pmid = {21820631}, issn = {1873-2585}, mesh = {Asbestos, Serpentine/*adverse effects ; *Environmental Exposure ; Environmental Pollutants/*adverse effects ; Humans ; Mesothelioma/chemically induced/*epidemiology ; Risk Factors ; }, abstract = {PURPOSE: There are different mineral classes of asbestos, including serpentines and amphiboles. Chrysotile is the main type of serpentine and by far the most frequently used type of asbestos (about 95% of world production and use). There has been continuing controversy over the capability of chrysotile asbestos to cause pleural and peritoneal mesothelioma. This review is to help clarify the issue by detailing cases and epidemiology studies worldwide where chrysotile is the exclusive or overwhelming fiber exposure.

METHODS: A worldwide literature review was conducted of asbestos and associated mesothelioma including case series, case-control and cohort epidemiology studies searching for well documented chrysotile asbestos associated mesothelioma cases.

RESULTS: Chrysotile asbestos exposures have occurred in many countries around the world from mining, manufacturing and community exposures. There have been many documented cases of mesothelioma from those exposures.

CONCLUSIONS: Chrysotile asbestos, along with all other types of asbestos, has caused mesothelioma and a world-wide ban of all asbestos is warranted to stop an epidemic of mesothelioma.}, } @article {pmid21817877, year = {2012}, author = {Kuschner, WG and Varma, R and Flores, R and Agrawal, M and Guvenc-Tuncturk, S}, title = {Missed opportunities to counsel patients with malignant pleural mesothelioma about causation and potential compensation.}, journal = {The American journal of the medical sciences}, volume = {343}, number = {3}, pages = {206-209}, doi = {10.1097/MAJ.0b013e3182297912}, pmid = {21817877}, issn = {1538-2990}, mesh = {Aged ; Aged, 80 and over ; Asbestos/adverse effects ; *Compensation and Redress ; *Counseling ; Female ; Humans ; Male ; Mesothelioma/*etiology ; Middle Aged ; Occupational Exposure/adverse effects ; Pleural Neoplasms/*etiology ; Retrospective Studies ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is a lethal malignancy strongly associated with occupational exposure to asbestos. The aims of this study were to assess the quality of counseling provided to patients with MPM about the causation of MPM and the potential for compensation.

METHODS: The authors conducted a structured retrospective chart review of patients with a diagnosis of MPM. They abstracted demographic data, occupational and environmental history and exposure data. They also searched for documentation of patient education and counseling.

RESULTS: The authors identified 16 patients with a new diagnosis of MPM during the study period. A job title was documented at least once in the records of 12 (75%) patients. Documentation of occupational exposure to asbestos was found in the records of 12 (75%) patients. Two patients (13%) were presumed to have had bystander exposure to asbestos. Education about MPM causation and counseling about opportunities for compensation were documented in the record of 1 patient (6%).

CONCLUSIONS: Among patients with MPM, documentation of some elements of an occupational history, including an occupational asbestos exposure history, was common. Advice to pursue compensation for potential occupation related MPM was rare. Physicians may be missing opportunities to provide beneficial information to patients with newly diagnosed MPM regarding potential legal redress and compensation.}, } @article {pmid21804121, year = {2011}, author = {Halmos, B and Powell, CA}, title = {Update in lung cancer and oncological disorders 2010.}, journal = {American journal of respiratory and critical care medicine}, volume = {184}, number = {3}, pages = {297-302}, pmid = {21804121}, issn = {1535-4970}, support = {R01 CA120174/CA/NCI NIH HHS/United States ; 1R01CA120174/CA/NCI NIH HHS/United States ; }, mesh = {Asbestos/*adverse effects ; Cause of Death/trends ; Coal/adverse effects ; Female ; Humans ; Incidence ; *Lung Neoplasms/diagnosis/etiology/mortality/therapy ; Male ; Mesothelioma/*etiology ; Mineral Fibers/adverse effects ; Smoke Inhalation Injury ; Tobacco Smoke Pollution/*adverse effects ; United States/epidemiology ; Wood/adverse effects ; }, } @article {pmid21798615, year = {2012}, author = {Wang, XR and Yu, IT and Qiu, H and Wang, MZ and Lan, YJ and Tse, LY and Yano, E and Christiani, DC}, title = {Cancer mortality among Chinese chrysotile asbestos textile workers.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {75}, number = {2}, pages = {151-155}, doi = {10.1016/j.lungcan.2011.06.013}, pmid = {21798615}, issn = {1872-8332}, mesh = {Adult ; Asbestos, Serpentine/*adverse effects ; China/epidemiology ; Humans ; Lung Neoplasms/mortality ; Middle Aged ; Neoplasms/*mortality ; Occupational Diseases/*mortality ; Prospective Studies ; Smoking/adverse effects ; *Textile Industry ; }, abstract = {To determine mortality associated with exposure to chrysotile asbestos, a cohort of asbestos workers from an asbestos textile factory in China was followed prospectively from 1972 to 2008. A total 577 workers were successfully followed, achieving a follow-up rate of 98.5% over 37 years. Employment data and smoking information were obtained from factory and individual workers. Vital status was ascertained from factory personnel records and the municipal death registry. Workers were categorized into high, medium and low exposure groups in terms of their job titles and workshops. Follow-up generated 17,508 person-years, with 259 deaths from all causes, 96 all cancers and 53 lung cancers and 2 mesotheliomas. The highest cancer mortality was observed in the high exposure group, with 1.5-fold age-adjusted mortality from all cancers and 2-fold from lung cancer compared to the low exposure group. Age and smoking adjusted hazard ratio in the high exposure group was 2.99 (95%CI, 1.30, 6.91) for lung cancer and 2.04 (1.12, 3.71) for all cancers. Both smokers and nonsmokers at the high exposure level had a high death risk of lung cancer, with a clearer exposure-response trend seen in smokers. This study confirmed increased mortality from lung cancer and all cancers in asbestos workers, and the cancer mortality was associated with exposure level.}, } @article {pmid21788493, year = {2011}, author = {Carbone, M and Baris, YI and Bertino, P and Brass, B and Comertpay, S and Dogan, AU and Gaudino, G and Jube, S and Kanodia, S and Partridge, CR and Pass, HI and Rivera, ZS and Steele, I and Tuncer, M and Way, S and Yang, H and Miller, A}, title = {Erionite exposure in North Dakota and Turkish villages with mesothelioma.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {108}, number = {33}, pages = {13618-13623}, pmid = {21788493}, issn = {1091-6490}, support = {NCI P01 114047//PHS HHS/United States ; }, mesh = {Air Pollutants/adverse effects ; Asbestos/adverse effects ; Environmental Exposure/*adverse effects ; Humans ; Mesothelioma/*chemically induced/epidemiology/etiology ; North Dakota/epidemiology ; Transportation ; Turkey/epidemiology ; United States ; Zeolites/*adverse effects ; }, abstract = {Exposure to erionite, an asbestos-like mineral, causes unprecedented rates of malignant mesothelioma (MM) mortality in some Turkish villages. Erionite deposits are present in at least 12 US states. We investigated whether increased urban development has led to erionite exposure in the United States and after preliminary exploration, focused our studies on Dunn County, North Dakota (ND). In Dunn County, ND, we discovered that over the past three decades, more than 300 miles of roads were surfaced with erionite-containing gravel. To determine potential health implications, we compared erionite from the Turkish villages to that from ND. Our study evaluated airborne point exposure concentrations, examined the physical and chemical properties of erionite, and examined the hallmarks of mesothelial cell transformation in vitro and in vivo. Airborne erionite concentrations measured in ND along roadsides, indoors, and inside vehicles, including school buses, equaled or exceeded concentrations in Boyali, where 6.25% of all deaths are caused by MM. With the exception of outdoor samples along roadsides, ND concentrations were lower than those measured in Turkish villages with MM mortality ranging from 20 to 50%. The physical and chemical properties of erionite from Turkey and ND are very similar and they showed identical biological activities. Considering the known 30- to 60-y latency for MM development, there is reason for concern for increased risk in ND in the future. Our findings indicate that implementation of novel preventive and early detection programs in ND and other erionite-rich areas of the United States, similar to efforts currently being undertaken in Turkey, is warranted.}, } @article {pmid21776278, year = {2011}, author = {Zarogoulidis, P and Orfanidis, M and Constadinidis, TC and Eleutheriadou, E and Kontakiotis, T and Kerenidi, T and Sakkas, L and Courcoutsakis, N and Zarogoulidis, K}, title = {A 26-year-old male with mesothelioma due to asbestos exposure.}, journal = {Case reports in medicine}, volume = {2011}, number = {}, pages = {951732}, pmid = {21776278}, issn = {1687-9635}, abstract = {Mesothelioma is a malignancy with poor prognosis, with an average 5-year survival rate being less than 9%. This type of cancer is almost exclusively caused by exposure to asbestos. A long exposure can cause mesothelioma and so can short ones, as each exposure is cumulative. We report a case of a 26-year-old male who was exposed to asbestos during his primary school years from the age of 6 to 12. Although the tumor mainly affects older men who in their youth were occupationally exposed to asbestos, malignant mesothelioma can also occur in young adults. A medical history was carefully taken and asbestos exposure was immediately mentioned by the patient. We conducted biopsy on the right supraclavicular lymph node. The patient was not a candidate for surgery, and chemotherapy treatment was initiated. While patient's chemotherapy is still ongoing, no other similar cases of students or teachers have been traced up to date from his school. The school building was demolished in January 2009.}, } @article {pmid21757252, year = {2012}, author = {Kao, SC and Harvie, R and Paturi, F and Taylor, R and Davey, R and Abraham, R and Clarke, S and Marx, G and Cullen, M and Kerestes, Z and Pavlakis, N}, title = {The predictive role of serum VEGF in an advanced malignant mesothelioma patient cohort treated with thalidomide alone or combined with cisplatin/gemcitabine.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {75}, number = {2}, pages = {248-254}, doi = {10.1016/j.lungcan.2011.06.007}, pmid = {21757252}, issn = {1872-8332}, mesh = {Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use ; C-Reactive Protein/analysis ; Cisplatin/administration & dosage/adverse effects ; Clinical Trials, Phase II as Topic ; Deoxycytidine/administration & dosage/adverse effects/analogs & derivatives ; Female ; Humans ; Male ; Mesothelioma/blood/*drug therapy/mortality ; Middle Aged ; Thalidomide/adverse effects/*therapeutic use ; Vascular Endothelial Growth Factor A/*blood ; Gemcitabine ; }, abstract = {There is a need for new treatment strategies and prognostic markers for the management of malignant mesothelioma (MM). The activity of thalidomide/cisplatin/gemcitabine (arm A) or thalidomide alone (arm B) was investigated in two parallel phase II studies in patients with advanced MM, using 6 month progression free survival (PFS) as the principal end-point. The predictive role of pre-treatment and 8 week follow-up serum C-reactive protein (CRP), interlukin-6 (IL-6), interlukin-6 soluble receptor (sIL-6R), mesothelin (SMRP) and vascular endothelial growth factor (VEGF) was also assessed. The proportion of patients with stable disease for >6 months was similar in both studies (arm A 35%, arm B 29%) and toxicity was mainly grade I/II. In univariate analyses only pre-treatment VEGF and CRP were correlated with survival. At 8 weeks post treatment, increased survival was found with low (median) VEGF and CRP (P<0.05). Change in VEGF over the first 8 weeks of treatment was also predictive for survival (P<0.05). When pre-treatment VEGF was >median, decreasing VEGF was associated with increased survival (P<0.05). In conclusion, thalidomide alone, or in combination with cisplatin/gemcitabine, controlled disease for >6 months in ∼30% of patients. Patients with decreasing VEGF during treatment had longest survival. Pre-treatment VEGF or CRP and early change in VEGF on treatment may predict treatment benefit and should be examined in future studies.}, } @article {pmid21749551, year = {2011}, author = {van Meerbeeck, JP and Damhuis, R}, title = {Facts, rumours and speculations about the mesothelioma epidemic.}, journal = {Respirology (Carlton, Vic.)}, volume = {16}, number = {7}, pages = {1018-1019}, doi = {10.1111/j.1440-1843.2011.02020.x}, pmid = {21749551}, issn = {1440-1843}, mesh = {Asbestos/*adverse effects ; Environmental Health/*trends ; Humans ; Lung Diseases/*chemically induced/*epidemiology ; }, } @article {pmid21742625, year = {2011}, author = {Nelson, G and Murray, J and Phillips, JI}, title = {The risk of asbestos exposure in South African diamond mine workers.}, journal = {The Annals of occupational hygiene}, volume = {55}, number = {6}, pages = {569-577}, doi = {10.1093/annhyg/mer028}, pmid = {21742625}, issn = {1475-3162}, mesh = {Air Pollutants, Occupational/*analysis/metabolism/toxicity ; Asbestos/*analysis/metabolism/toxicity ; Asbestos, Amphibole/analysis ; Asbestosis/epidemiology/*pathology ; Autopsy ; Databases as Topic ; Diamond ; Environmental Monitoring ; Epidemiological Monitoring ; Female ; Humans ; Lung/chemistry/metabolism ; Male ; Mesothelioma/chemically induced/epidemiology ; Mineral Fibers/analysis/toxicity ; *Mining ; Occupational Exposure/adverse effects/*analysis/statistics & numerical data ; Pleura/pathology ; Risk Assessment ; Soil Pollutants/analysis ; South Africa/epidemiology ; Talc/analysis ; Workers' Compensation ; }, abstract = {OBJECTIVES: Asbestos is associated with South African diamond mines due to the nature of kimberlite and the location of the diamond mines in relation to asbestos deposits. Very little is known about the health risks in the diamond mining industry. The objective of this study was to explore the possibility of asbestos exposure during the process of diamond mining.

METHODS: Scanning electron microscopy and energy-dispersive X-ray spectroscopy analysis were used to identify asbestos fibres in the lungs of diamond mine workers who had an autopsy for compensation purposes and in the tailings and soils from three South African diamond mines located close to asbestos deposits. The asbestos lung fibre burdens were calculated. We also documented asbestos-related pathological findings in diamond mine workers at autopsy.

RESULTS: Tremolite-actinolite asbestos fibres were identified in the lungs of five men working on diamond mines. Tremolite-actinolite and/or chrysotile asbestos were present in the mine tailings of all three mines. Mesothelioma, asbestosis, and/or pleural plaques were diagnosed in six diamond mine workers at autopsy.

CONCLUSIONS: These findings indicate that diamond mine workers are at risk of asbestos exposure and, thus, of developing asbestos-related diseases. South Africa is a mineral-rich country and, when mining one commodity, it is likely that other minerals, including asbestos, will be accidentally mined. Even at low concentrations, asbestos has the potential to cause disease, and mining companies should be aware of the health risk of accidentally mining it. Recording of comprehensive work histories should be mandatory to enable the risk to be quantified in future studies.}, } @article {pmid21742624, year = {2011}, author = {Burdorf, A and Heederik, D}, title = {Applying quality criteria to exposure in asbestos epidemiology increases the estimated risk.}, journal = {The Annals of occupational hygiene}, volume = {55}, number = {6}, pages = {565-568}, doi = {10.1093/annhyg/mer042}, pmid = {21742624}, issn = {1475-3162}, mesh = {Asbestos/*adverse effects ; Bias ; Carcinogens, Environmental/adverse effects ; Epidemiologic Methods ; Female ; Humans ; Inhalation Exposure/*statistics & numerical data ; Lung Neoplasms/epidemiology ; Male ; Mesothelioma/epidemiology ; Meta-Analysis as Topic ; Netherlands/epidemiology ; Occupational Exposure/*statistics & numerical data ; Pleural Neoplasms/epidemiology ; Research Design/*standards ; Risk Assessment ; }, abstract = {Mesothelioma deaths due to environmental exposure to asbestos in The Netherlands led to parliamentary concern that exposure guidelines were not strict enough. The Health Council of the Netherlands was asked for advice. Its report has recently been published. The question of quality of the exposure estimates was studied more systematically than in previous asbestos meta-analyses. Five criteria of quality of exposure information were applied, and cohort studies that failed to meet these were excluded. For lung cancer, this decreased the number of cohorts included from 19 to 3 and increased the risk estimate 3- to 6-fold, with the requirements for good historical data on exposure and job history having the largest effects. It also suggested that the apparent differences in lung cancer potency between amphiboles and chrysotile may be produced by lower quality studies. A similar pattern was seen for mesothelioma. As a result, the Health Council has proposed that the occupational exposure limit be reduced from 10 000 fibres m(-3) (all types) to 250 f m(-3) (amphiboles), 1300 f m(-3) (mixed fibres), and 2000 f m(-3) (chrysotile). The process illustrates the importance of evaluating quality of exposure in epidemiology since poor quality of exposure data will lead to underestimated risk.}, } @article {pmid21742237, year = {2011}, author = {Ferretti, G}, title = {[What are the tools for post-occupational follow-up, how should they be performed and what are their performance, limits and benefit/risk ratio? Chest X-Ray and CT scan].}, journal = {Revue des maladies respiratoires}, volume = {28}, number = {6}, pages = {761-772}, doi = {10.1016/j.rmr.2011.02.012}, pmid = {21742237}, issn = {1776-2588}, mesh = {Asbestosis/*diagnostic imaging/etiology/pathology ; Clinical Trials as Topic ; Cohort Studies ; Data Collection ; Follow-Up Studies ; Humans ; Lung/diagnostic imaging/pathology ; Mass Screening ; Observer Variation ; Pleura/diagnostic imaging/pathology ; Population Surveillance/*methods ; Practice Guidelines as Topic ; *Radiography, Thoracic/adverse effects/methods/statistics & numerical data ; Reproducibility of Results ; Research Design ; Respiratory Tract Neoplasms/diagnostic imaging/etiology ; Retirement ; Risk Assessment ; Sensitivity and Specificity ; *Tomography, X-Ray Computed/adverse effects/methods/statistics & numerical data ; }, abstract = {Chest radiography and computed tomography (CT) are the two radiological techniques used for the follow-up of people exposed to asbestos. Since the last conference of consensus (1999), the scientific literature has primarily covered high-resolution CT and high-resolution volume CT (HR-VCT). We consider in turn the contribution of digital thoracic radiography, recommendations for the performance of HR-VCT to ensure the quality of examination while controlling the delivered radiation dose, and the need to refer to the "CT atlas of benign diseases related to asbestos exposure", published by a group of French experts in 2007, for interpretation. The results of the published studies concerning radiography or CT are then reviewed. We note the great interobserver variability in the recognition of pleural plaques and asbestosis, indicating the need for adequate training of radiologists, and the importance of defining standardized, quantified criteria for CT abnormalities. The very low agreement between thoracic and general radiologists must be taken into account. The reading of CT scans in cases of occupational exposure to asbestos should be entrusted to thoracic radiologists or to general radiologists having validated specific training. A double interpretation of CT could be considered in medicosocial requests. CT is more sensitive than chest radiography in the detection of bronchial carcinoma but generates a great number of false positive results (96 to 99%). No scientific data are available to assess the role of imaging by either CT or chest radiography in the early detection of mesothelioma.}, } @article {pmid21742228, year = {2011}, author = {Ameille, J and Brochard, P and Letourneux, M and Paris, C and Pairon, JC}, title = {Asbestos-related cancer risk in patients with asbestosis or pleural plaques.}, journal = {Revue des maladies respiratoires}, volume = {28}, number = {6}, pages = {e11-7}, doi = {10.1016/j.rmr.2011.04.008}, pmid = {21742228}, issn = {1776-2588}, mesh = {Asbestos/*adverse effects ; Asbestosis/*epidemiology ; Confounding Factors, Epidemiologic ; Disease Progression ; Disease Susceptibility ; Dose-Response Relationship, Drug ; Environmental Exposure ; Fibrosis ; Follow-Up Studies ; Humans ; Lung Neoplasms/*epidemiology/etiology ; Mesothelioma/*epidemiology/etiology ; Occupational Exposure ; Occupations/statistics & numerical data ; Pleura/*pathology ; Pleural Neoplasms/*epidemiology/etiology ; Risk ; }, abstract = {INTRODUCTION: The relationships between benign asbestos-related diseases (asbestosis and pleural plaques) and thoracic cancers are still debated. The aim of this paper was to review the epidemiological data relevant to this issue.

CURRENT KNOWLEDGE: Published studies show a significant relationship between occupational exposure to asbestos and lung cancer risk, even in the absence of abnormalities consistent with asbestosis on the postero-anterior chest x-ray. For a given cumulative asbestos exposure, the presence of radiographic evidence of asbestosis is associated with an increased risk of lung cancer. Among asbestos-exposed individuals, those having radiographic evidence of pleural plaques are at increased risk for lung cancer and pleural mesothelioma, compared to the general population. However, there is no evidence that pleural plaque confers an increased risk of lung cancer or pleural mesothelioma within a population of individuals having the same cumulative asbestos exposure.

PERSPECTIVES: The studies identified for this review relied only on chest radiograph data. Studies involving accurate evaluations of asbestos exposure and computed tomography of the chest are needed.

CONCLUSION: Currently available data indicate that patient follow-up modalities should be dictated solely by the estimated cumulative asbestos exposure and not by the existence of pleural plaques.}, } @article {pmid21739769, year = {2011}, author = {Bagheri, R and Haghi, SZ and Rahim, MB and Attaran, D and Toosi, MS}, title = {Malignant pleural mesothelioma: clinicopathologic and survival characteristic in a consecutive series of 40 patients.}, journal = {Annals of thoracic and cardiovascular surgery : official journal of the Association of Thoracic and Cardiovascular Surgeons of Asia}, volume = {17}, number = {2}, pages = {130-136}, doi = {10.5761/atcs.oa.09.01427}, pmid = {21739769}, issn = {2186-1005}, abstract = {INTRODUCTION: Pleural malignant mesothelioma is an uncommon but extremely invasive tumor which originates from mesothelial cells and usually occurs after prolonged exposure to asbestos. Different types of surgical and oncological therapeutic methods have been used resulting in various outcomes. The aim of this study was to evaluate, clinicopathologically, 40 patients with pleural malignant mesothelioma and the main factors influencing their prognosis.

METHODS: In this study, 40 patients with a definitive diagnosis, who had been followed up for at least 3 years were studied according to these: epidemiologic factors, stage and pathological types, treatment method and complications, and by using factors that influence patients survival, we evaluated them statistically.

RESULTS: The M/F ratio was l3/1 with an average age of 55 years. Chest pain was the most common symptom. In 55% of patients, the lesions were localized in the left site and most were in Buchart stage I or II. The epithelial form was the most common pathological pattern (62.5%). 47.5% of patients only received radiotherapy and chemotherapy. Of patients who underwent decortication and pleurectomy with adjuvant therapy, extrapleural was performed in 20% of patients, and pneumonectomy, in 17.5%; and 15% refused any type of treatment. One patient died from the surgery. The most common surgical complication was wound infection. The average survival was 10.5 months, and the main factors influencing the survival were physiologic status, pathological form of disease, stage of disease and the pattern of pleural involvement.

CONCLUSION: Because of the low survival after multimodality invasive treatments in mesothelioma, aggressive therapeutic methods were recommended in patients with good physiological status and early clinical stage with a good pathology type.}, } @article {pmid21737558, year = {2011}, author = {Musk, AW and Olsen, N and Alfonso, H and Reid, A and Mina, R and Franklin, P and Sleith, J and Hammond, N and Threlfall, T and Shilkin, KB and de Klerk, NH}, title = {Predicting survival in malignant mesothelioma.}, journal = {The European respiratory journal}, volume = {38}, number = {6}, pages = {1420-1424}, doi = {10.1183/09031936.00000811}, pmid = {21737558}, issn = {1399-3003}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Female ; Humans ; Male ; Mesothelioma/*mortality/pathology ; Middle Aged ; Peritoneal Neoplasms/mortality/*pathology ; Pleural Neoplasms/*mortality/pathology ; Registries ; Sex Factors ; Survival Analysis ; Western Australia/epidemiology ; Young Adult ; }, abstract = {Malignant mesothelioma (MM) of the pleura or peritoneum is a universally fatal disease attracting an increasing range of medical interventions and escalating healthcare costs. Changes in survival and the factors affecting survival of all patients ever diagnosed with MM in Western Australia over the past five decades and confirmed by the Western Australian Mesothelioma Registry to December 2005 were examined. Sex, age, date and method of diagnosis, site of disease and histological type were recorded. Date of onset of symptoms and performance status were obtained from clinical notes for a sample of cases. Cox regression was used to examine the association of the clinical variables and the 10-yr periods of disease onset with survival after diagnosis. Survival was inversely related to age, being worse for males (hazard ratio (HR) 1.4, 95% CI 1.2-1.6), and those with peritoneal mesothelioma (HR 1.4, 95% CI 1.1-1.7). Patients with sarcomatoid histology had worse prognosis than patients with epithelioid and biphasic histological subtypes. Survival improved after the 1970s and has made incremental improvements since then. Median (interquartile range) survival by decade, from 1960 until 2005, was 64 (0-198), 177 (48-350), 221 (97-504), 238 (108-502) and 301 (134-611) days; ~4 weeks of this apparent improvement can be attributed to earlier diagnosis. With increasing resources and treatment costs for MM over the past 40 yrs, there have been modest improvements in survival but no complete remissions.}, } @article {pmid21721837, year = {2011}, author = {Stella, GM}, title = {Carbon nanotubes and pleural damage: perspectives of nanosafety in the light of asbestos experience.}, journal = {Biointerphases}, volume = {6}, number = {2}, pages = {P1-17}, doi = {10.1116/1.3582324}, pmid = {21721837}, issn = {1559-4106}, mesh = {Asbestos/toxicity ; Humans ; Mesothelioma/*chemically induced/prevention & control ; Models, Biological ; Nanotubes, Carbon/*toxicity ; Occupational Exposure/*prevention & control ; *Occupational Health ; Pleura/*drug effects ; Pleural Neoplasms/*chemically induced/prevention & control ; }, abstract = {Carbon nanotubes are molecular-scale one-dimensional manufactured materials which display several potential applications in engineering and materials science. Burgeoning evidence demonstrates that carbon nanotubes and asbestos share comparable physical properties. Therefore carbon nanotubes might display toxic effects and the extent of the toxicity is more specifically directed to lung and pleura. These effects are related to properties of carbon nanotubes, such as their structure, length, aspects ratio, surface area, degree of aggregation, extent of oxidation, bound functional group, method of manufacturing, concentration and dose. At the present there is no global agreement about the risk of carbon nanotubes on human health and in particular on their transformation capacity. Safety concerns regarding carbon nanotubes can be ameliorated. In this context, it is important to put the known hazards of carbon nanotubes into perspective. Here is presented an overview about toxicity issues in the application of carbon nanotubes to biological systems, taking into consideration the already known asbestos-induced mechanisms of biological damages.}, } @article {pmid23393811, year = {2011}, author = {Mensi, C and Sieno, C and De Matteis, S and Consonni, D and Riboldi, L and Bertazzi, PA}, title = {[Incidence of malignant mesothelioma and asbestos exposure in the Lombardy region, Italy, 2000-2008].}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {33}, number = {3 Suppl}, pages = {96-98}, pmid = {23393811}, issn = {1592-7830}, mesh = {Asbestos/*adverse effects ; Female ; Humans ; Incidence ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology ; Occupational Diseases/*epidemiology ; Occupational Exposure/*adverse effects ; Time Factors ; }, abstract = {We evaluated the trend of incidence and asbestos exposure of malignant mesothelioma (MM) in 2000-2008 in the Lombardy Region (Italy). We recorded 2,816 MMs (1,793 men, 1,023 women). The age-standardized rates (x 100,000/year) were 3.4 (men) and 1.4 (women) (standard population: Europe). We found a 3.0% and 0.9% increase per year of number of cases and rate, respectively. Exposure was obtained in 2,671 cases (94.9%). Occupational exposure to asbestos was found for 1,296 (72.3%) men and 377 (36.9%) women, non-occupational exposure in 141 (13.8%) women and 58 (3.2%) men. The exposure profile within gender did not vary over years.}, } @article {pmid21710492, year = {2011}, author = {Shukla, A and Hillegass, JM and MacPherson, MB and Beuschel, SL and Vacek, PM and Butnor, KJ and Pass, HI and Carbone, M and Testa, JR and Heintz, NH and Mossman, BT}, title = {ERK2 is essential for the growth of human epithelioid malignant mesotheliomas.}, journal = {International journal of cancer}, volume = {129}, number = {5}, pages = {1075-1086}, pmid = {21710492}, issn = {1097-0215}, support = {T32 ES007122-30/ES/NIEHS NIH HHS/United States ; T32ES07122/ES/NIEHS NIH HHS/United States ; P01 CA114047-04/CA/NCI NIH HHS/United States ; P01CA114047/CA/NCI NIH HHS/United States ; P30CA006927/CA/NCI NIH HHS/United States ; P30 CA006927/CA/NCI NIH HHS/United States ; T32 ES007122/ES/NIEHS NIH HHS/United States ; P01 CA114047/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Apoptosis/drug effects ; Biomarkers, Tumor/genetics/metabolism ; Blotting, Western ; Butadienes/pharmacology ; Cell Adhesion/drug effects ; Cell Line, Tumor ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Gene Expression Profiling ; Humans ; Immunoenzyme Techniques ; Mesothelioma/drug therapy/*metabolism/*pathology ; Mice ; Mice, SCID ; Mitogen-Activated Protein Kinase 1/antagonists & inhibitors/genetics/*metabolism ; Mitogen-Activated Protein Kinase 3/antagonists & inhibitors/genetics/*metabolism ; Nitriles/pharmacology ; Oligonucleotide Array Sequence Analysis ; Pleural Neoplasms/drug therapy/metabolism/pathology ; RNA, Messenger/genetics ; RNA, Small Interfering/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Xenograft Model Antitumor Assays ; }, abstract = {Members of the extracellular signal-regulated kinase (ERK) family may have distinct roles in the development of cell injury and repair, differentiation and carcinogenesis. Here, we show, using a synthetic small-molecule MEK1/2 inhibitor (U0126) and RNA silencing of ERK1 and 2, comparatively, that ERK2 is critical to transformation and homeostasis of human epithelioid malignant mesotheliomas (MMs), asbestos-induced tumors with a poor prognosis. Although MM cell (HMESO) lines stably transfected with shERK1 or shERK2 both exhibited significant decreases in cell proliferation in vitro, injection of shERK2 cells, and not shERK1 cells, into immunocompromised severe combined immunodeficiency (SCID) mice showed significant attenuated tumor growth in comparison to shControl (shCon) cells. Inhibition of migration, invasion and colony formation occurred in shERK2 MM cells in vitro, suggesting multiple roles of ERK2 in neoplasia. Microarray and quantitative real-time PCR analyses revealed gene expression that was significantly increased (CASP1, TRAF1 and FAS) or decreased (SEMA3E, RPS6KA2, EGF and BCL2L1) in shERK2-transfected MM cells in contrast to shCon-transfected MM cells. Most striking decreases were observed in mRNA levels of Semaphorin 3 (SEMA3E), a candidate tumor suppressor gene linked to inhibition of angiogenesis. These studies demonstrate a key role of ERK2 in novel gene expression critical to the development of epithelioid MMs. After injection of sarcomatoid human MM (PPMMill) cells into SCID mice, both shERK1 and shERK2 lines showed significant decreased tumor growth, suggesting heterogeneous effects of ERKs in individual MMs.}, } @article {pmid21701776, year = {2011}, author = {Wen, G and Hong, M and Li, B and Liao, W and Cheng, SK and Hu, B and Calaf, GM and Lu, P and Partridge, MA and Tong, J and Hei, TK}, title = {Transforming growth factor-β-induced protein (TGFBI) suppresses mesothelioma progression through the Akt/mTOR pathway.}, journal = {International journal of oncology}, volume = {39}, number = {4}, pages = {1001-1009}, pmid = {21701776}, issn = {1791-2423}, support = {R01 ES005786/ES/NIEHS NIH HHS/United States ; P01 CA049062/CA/NCI NIH HHS/United States ; P30 ES09089/ES/NIEHS NIH HHS/United States ; P42 ES010349/ES/NIEHS NIH HHS/United States ; P30 ES009089/ES/NIEHS NIH HHS/United States ; F32 ES005786/ES/NIEHS NIH HHS/United States ; CA49062/CA/NCI NIH HHS/United States ; P42 ES10349/ES/NIEHS NIH HHS/United States ; ES05786/ES/NIEHS NIH HHS/United States ; }, mesh = {Asbestos/toxicity ; Cell Cycle/drug effects ; Cell Growth Processes/*drug effects ; Cell Line ; Cell Line, Tumor ; Cyclin D1/metabolism ; DNA-Binding Proteins/metabolism ; Disease Progression ; Epidermal Growth Factor/metabolism ; Extracellular Matrix Proteins/antagonists & inhibitors/genetics/*metabolism ; Gene Knockdown Techniques/methods ; Humans ; Mesothelioma/etiology/genetics/*metabolism/pathology ; Mutation ; Neoplasms, Mesothelial/genetics/metabolism/pathology ; Oncogene Proteins v-mos/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Protein Biosynthesis/drug effects ; Proto-Oncogene Proteins c-akt/*metabolism ; RNA, Small Interfering/administration & dosage/genetics ; Signal Transduction/drug effects ; TOR Serine-Threonine Kinases/*metabolism ; Transcription Factors/metabolism ; Transforming Growth Factor beta/antagonists & inhibitors/genetics/*metabolism ; }, abstract = {As an uncommon cancer, mesothelioma is very hard to treat with a low average survival rate owing to its usual late detection and being highly invasive. The link between asbestos exposure and the development of mesothelioma in humans is unequivocal. TGFBI, a secreted protein that is induced by transforming growth factor-β in various human cell types, has been shown to be associated with tumorigenesis in various types of tumors. It has been demonstrated that TGFBI expression is markedly suppressed in asbestos-induced tumorigenic cells, while an ectopic expression of TGFBI significantly suppresses tumorigenicity and progression in human bronchial epithelial cells. In order to delineate a potential role of TGFBI in mediating the molecular events that occur in mesothelioma tumorigenesis, we generated stable TGFBI knockdown mutants from the mesothelium cell line Met-5A by using an shRNA approach, and secondly created ectopic TGFBI overexpression mutants from the mesothelioma cell line H28 in which TGFBI is absent. We observed that in the absence of TGFBI, the knockdown mesothelial and mesothelioma cell lines exhibited an elevated proliferation rate, enhanced plating efficiency, increased anchorage-independent growth, as well as an increased cellular protein synthesis rate as compared with their respective controls. Furthermore, cell cycle regulatory proteins c-myc/cyclin D1/phosphor-Rb were upregulated; a more active PI3K/Akt/mTOR signaling pathway was also detected in TGFBI-depleted cell lines. These findings suggest that TGFBI may repress mesothelioma tumorigenesis and progression via the PI3K/Akt signaling pathway.}, } @article {pmid21701088, year = {2011}, author = {Toyokuni, S and Jiang, L and Hu, Q and Nagai, H and Okazaki, Y and Akatsuka, S and Yamashita, Y}, title = {[Mechanisms of asbestos-induced carcinogenesis].}, journal = {Nihon eiseigaku zasshi. Japanese journal of hygiene}, volume = {66}, number = {3}, pages = {562-567}, doi = {10.1265/jjh.66.562}, pmid = {21701088}, issn = {0021-5082}, mesh = {Animals ; Asbestosis/*etiology ; Humans ; Mesothelioma/*etiology ; Pleural Neoplasms/*etiology ; }, abstract = {Several types of fibrous stone called asbestos have been an unexpected cause of human cancer in the history. This form of mineral is considered precious in that they are heat-, friction-, and acid-resistant, are obtained easily from mines, and can be modified to any form with many industrial merits. However, it became evident that the inspiration of asbestos causes a rare cancer called malignant mesothelioma. Because of the long incubation period, the peak year for malignant mesothelioma is expected to be 2025 in Japan. Thus, it is necessary to elucidate the mechanisms of asbestos-induced mesothelial carcinogenesis. In this review, we summarize the cutting edge results of our 5-year project funded by a MEXT grant, in which local iron deposition and the characteristics of mesothelial cells are the key issues.}, } @article {pmid21701087, year = {2011}, author = {Hasegawa, S and Tanaka, F and Okada, M and Yamanaka, T and Kamikonya, N and Soejima, T and Tsujimura, T and Fukuoka, K and Nakano, T}, title = {[Current status and future direction of Japan's clinical trial for malignant pleural mesothelioma].}, journal = {Nihon eiseigaku zasshi. Japanese journal of hygiene}, volume = {66}, number = {3}, pages = {558-561}, doi = {10.1265/jjh.66.558}, pmid = {21701087}, issn = {0021-5082}, mesh = {Combined Modality Therapy ; Humans ; Mesothelioma/*therapy ; Pleural Neoplasms/*therapy ; Prospective Studies ; }, abstract = {The feasibility and efficacy of trimodality therapy for malignant pleural mesothelioma (MPM) are still controversial mainly due to the lack of clinical evidence. Although three major clinical trials on this therapy have been recently reported from North America and Europe, it remains unclear whether results in Caucasian populations may be directly applicable to Asian populations. In this context, as a project of the "Comprehensive approach on asbestos-related diseases" supported by the "Special Coordination Fund for Promoting Science and Technology of MEXT, Japan", a prospective multi-institutional study has been planned to evaluate the feasibility of induction chemotherapy using pemetrexed plus cisplatin, followed by extrapleural pneumonectomy (EPP) and postoperative hemithoracic radiation in patients with resectable MPM. Primary endpoints are macroscopic complete resection rate by EPP and treatment-related mortality for trimodality therapy. The study was initiated in May 2008 and patient enrollment was finished in November 2010.}, } @article {pmid21701086, year = {2011}, author = {Fukuoka, K and Tanaka, F and Tsujimura, T and Hashimoto-Tamaoki, T and Hasegawa, S and Nakano, T}, title = {[Exploratory study on the detection of markers for diagnosing early-stage malignant mesothelioma].}, journal = {Nihon eiseigaku zasshi. Japanese journal of hygiene}, volume = {66}, number = {3}, pages = {553-557}, doi = {10.1265/jjh.66.553}, pmid = {21701086}, issn = {0021-5082}, mesh = {Biomarkers, Tumor/*analysis ; Glycoproteins/blood ; Humans ; Mesothelioma/*diagnosis ; Pleural Effusion/diagnosis ; Pleural Effusion, Malignant/diagnosis ; Pleural Neoplasms/diagnosis ; }, abstract = {Malignant mesothelioma (MM) is a highly aggressive, incurable neoplasm associated with asbestos exposure. Early detection of MM is not easy and radiological surveillance is imperfect. The use of blood-based biomarkers might solve this difficulty and allow detection of MM at an early stage when combined treatment involving surgery, chemotherapy and radiotherapy might be effective. In the research project entitled "Comprehensive approach on asbestos-related diseases" supported by the "Special Coordination Funds for Promoting Science and Technology (H18-1-3-3-1)", we conducted an exploratory study on the detection of markers for diagnosing early-stage MM. In this study, we have shown that serum soluble mesothelin-related peptide (SMRP) is a highly specific and moderately sensitive biomarker for diagnosing MM. SMRP levels in pleural effusion were elevated not only in advanced-stage malignant pleural mesothelioma (MPM), but also in early-stage disease. SMRP in pleural effusion can be an MPM-specific biomarker with greater sensitivity than in serum, especially for the early stage of the disease. Circulating tumor cells (CTCs) and circulating endothelial cells (CECs) were considered to be useful surrogate markers of disease progression in MPM, although the lack of sensitivity for early-stage disease remains to be improved. Cytological analysis with gene expression profiling has been more effective in detecting early-stage MPM with pleural effusion. In conclusion, blood or effusion-based biomarkers, possibly in combination with other new modalities, such as a thoracoscopy combined with the advanced imaging systems consisting of autofluorescence imaging (AFI) and narrow band imaging (NBI), will show some promise for curing MPM if the disease is detected at an early stage.}, } @article {pmid21701085, year = {2011}, author = {Otsuki, T and Nakano, T and Hasegawa, S and Okada, M and Tsujimura, T and Sekido, Y and Toyokuni, S and Nishimoto, H and Fukuoka, K and Tanaka, F and Kumagai, N and Maeda, M and Nishimura, Y}, title = {[Archives of "comprehensive approach on asbestos-related diseases" supported by the "special coordination funds for promoting science and technology (H18-1-3-3-1)"-- overview of group research project, care and specimen registration, cellular characteristics of mesothelioma and immunological effects of asbestos].}, journal = {Nihon eiseigaku zasshi. Japanese journal of hygiene}, volume = {66}, number = {3}, pages = {543-552}, doi = {10.1265/jjh.66.543}, pmid = {21701085}, issn = {0021-5082}, mesh = {Animals ; Asbestos/*immunology ; Humans ; Mesothelioma/*immunology/pathology ; Registries ; Research ; }, abstract = {The research project entitled "Comprehensive approach on asbestos-related diseases" supported by the "Special Coordination Funds for Promoting Science and Technology (H18-1-3-3-1)" began in 2006 and was completed at the end of the Japanese fiscal year of 2010. This project included four parts; (1) malignant mesothelioma (MM) cases and specimen registration, (2) development of procedures for the early diagnosis of MM, (3) commencement of clinical investigations including multimodal approaches, and (4) basic research comprising three components; (i) cellular and molecular characterization of mesothelioma cells, (ii) immunological effects of asbestos, and (iii) elucidation of asbestos-induced carcinogenesis using animal models. In this special issue of the Japanese Journal of Hygiene, we briefly introduce the achievements of our project. The second and third parts and the third component of the fourth part are described in other manuscripts written by Professors Fukuoka, Hasegawa, and Toyokuni. In this manuscript, we introduce a brief summary of the first part "MM cases and specimen registration", the first component of the fourth part "Cellular and molecular characterization of mesothelioma cells" and the second component of the fourth part "Immunological effects of asbestos". In addition, a previous special issue presented by the Study Group of Fibrous and Particulate Substances (SGFPS) (chaired by Professor Otsuki, Kawasaki Medical School, Japan) for the Japanese Society of Hygiene and published in Environmental Health and Preventive Medicine Volume 13, 2008, included reviews of the aforementioned first component of the fourth part of the project. Taken together, our project led medical investigations regarding asbestos and MM progress and contributed towards the care and examination of patients with asbestos-related diseases during these five years. Further investigations are required to facilitate the development of preventive measures and the cure of asbestos-related diseases, particularly in Japan, where asbestos-related diseases are predicted to increase in the next 10 to 20 years.}, } @article {pmid21692685, year = {2011}, author = {Yamada, S and Tabata, C and Tabata, R and Fukuoka, K and Nakano, T}, title = {Clinical significance of pleural effusion mesothelin in malignant pleural mesothelioma.}, journal = {Clinical chemistry and laboratory medicine}, volume = {49}, number = {10}, pages = {1721-1726}, doi = {10.1515/CCLM.2011.242}, pmid = {21692685}, issn = {1437-4331}, mesh = {Aged ; Enzyme-Linked Immunosorbent Assay ; Female ; GPI-Linked Proteins/analysis/*metabolism ; Humans ; Lung Neoplasms/*diagnosis/pathology ; Male ; Mesothelin ; Mesothelioma/*diagnosis/pathology ; Pleural Effusion/*pathology ; Pleural Neoplasms/*diagnosis/pathology ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive malignant tumor of mesothelial origin associated with asbestos exposure. MPM has a limited response to conventional chemotherapy and radiotherapy, so early diagnosis of MPM is very important. This study investigated the pleural effusion mesothelin levels in patients with MPM and compared them to those of a population with a non-malignant pleuritis or lung cancer involving malignant pleural effusion.

METHODS: The pleural effusion mesothelin concentrations were measured in 45 MPM patients and 53 non-MPM individuals (24 individuals with non-malignant pleural effusions and 29 individuals with lung cancer involving malignant pleural effusion).

RESULTS: This study demonstrated that patients with MPM had significantly higher pleural effusion mesothelin levels than a population with non-malignant pleuritis or lung cancer involving malignant pleural effusion. The difference in overall survival between the groups with pleural effusion mesothelin levels lower and higher than the assumed cut-off of 10 nM was significant.

CONCLUSIONS: The data suggest that the pleural effusion mesothelin concentration could be useful as an aid for the diagnosis of MPM.}, } @article {pmid21682033, year = {2011}, author = {Duell, T}, title = {[Asbestos-induced malignant pulmonary and pleural diseases].}, journal = {MMW Fortschritte der Medizin}, volume = {153}, number = {22}, pages = {38-41}, doi = {10.1007/BF03368478}, pmid = {21682033}, issn = {1438-3276}, mesh = {Asbestosis/*diagnostic imaging/pathology/therapy ; Combined Modality Therapy ; Humans ; *Image Processing, Computer-Assisted ; Lung/diagnostic imaging/pathology ; Lung Neoplasms/*diagnostic imaging/*pathology/therapy ; Mesothelioma/*diagnostic imaging/pathology/therapy ; Palliative Care ; Pleural Neoplasms/*diagnostic imaging/pathology/therapy ; Prognosis ; *Tomography, X-Ray Computed ; }, } @article {pmid21671853, year = {2011}, author = {Marsh, GM and Youk, AO and Roggli, VL}, title = {Asbestos fiber concentrations in the lungs of brake repair workers: commercial amphiboles levels are predictive of chrysotile levels.}, journal = {Inhalation toxicology}, volume = {23}, number = {12}, pages = {681-688}, doi = {10.3109/08958378.2011.580472}, pmid = {21671853}, issn = {1091-7691}, mesh = {Asbestos, Amphibole/*chemistry/*toxicity ; Asbestos, Serpentine/*chemistry/*toxicity ; Automobiles ; Data Interpretation, Statistical ; Dust ; Humans ; Logistic Models ; Lung/*chemistry ; Lung Neoplasms/chemically induced ; Mineral Fibers/analysis ; Occupational Diseases/etiology ; Occupational Exposure ; }, abstract = {OBJECTIVES: To investigate the impact of extreme data points in Finkelstein's 2009 findings of no association between lung levels of commercial and non-commercial amphiboles (principally tremolite as a marker for chrysotile asbestos) in brake repair workers with mesothelioma.

METHODS: We first identified potential outliers, high leverage points, and influential points among lung levels of commercial amphiboles and tremolite among 15 persons whose only known exposure to asbestos was through brake repair work. We used sensitivity analysis and quantile regression to account for extreme data points and model commercial amphibole levels as a predictor of tremolite levels. We also used quantile regression to evaluate whether case-reported duration of employment as a brake repair worker predicted lung levels of commercial amphiboles or tremolite.

RESULTS: We found lung levels of commercial amphiboles are a statistically significant predictor of tremolite levels via sensitivity analysis (r = 0.82, slope estimate P-value = 0.001, R² = 0.68) and quantile regression (slope estimate P-value <0.0001). Our data provide no evidence that duration of employment as a brake repair worker was a predictor of lung levels of tremolite or commercial amphiboles.

CONCLUSIONS: Our findings suggest that elevated lung levels of tremolite in the lungs of brake repair workers with elevated levels of amphiboles arose from concurrent exposures to commercial amphibole and chrysotile asbestos in occupational settings other than brake repair work. These findings are supported by five new cases. The weight of the scientific evidence does not support a role for occupational exposure to brake dust and other friction products in the development of mesothelioma.}, } @article {pmid21671249, year = {2011}, author = {Egilman, D}, title = {An elaboration of "proof" of peritoneal mesothelioma from tremolite free chrysotile.}, journal = {American journal of industrial medicine}, volume = {54}, number = {8}, pages = {647}, doi = {10.1002/ajim.20975}, pmid = {21671249}, issn = {1097-0274}, mesh = {Asbestos, Serpentine/*toxicity ; Humans ; Male ; Mesothelioma/*epidemiology ; Occupational Diseases/*epidemiology ; Occupational Exposure/*adverse effects ; Peritoneal Neoplasms/*epidemiology ; }, } @article {pmid21656164, year = {2012}, author = {Buommino, E and De Filippis, A and Nicoletti, R and Menegozzo, M and Menegozzo, S and Ciavatta, ML and Rizzo, A and Brancato, V and Tufano, MA and Donnarumma, G}, title = {Cell-growth and migration inhibition of human mesothelioma cells induced by 3-O-methylfunicone from Penicillium pinophilum and cisplatin.}, journal = {Investigational new drugs}, volume = {30}, number = {4}, pages = {1343-1351}, pmid = {21656164}, issn = {1573-0646}, mesh = {Antineoplastic Combined Chemotherapy Protocols/pharmacology/*therapeutic use ; Cell Line, Tumor ; Cell Movement/*drug effects ; Cell Proliferation/drug effects ; Cell Shape/drug effects ; Chemotaxis/drug effects/genetics ; Cisplatin/*pharmacology/therapeutic use ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Matrix Metalloproteinase 2/genetics/metabolism ; Mesothelioma/*drug therapy/genetics/*pathology ; Penicillium/*chemistry ; Pyrones/*pharmacology/therapeutic use ; RNA, Messenger/genetics/metabolism ; Receptors, Vitronectin/genetics/metabolism ; Vascular Endothelial Growth Factor A/genetics/metabolism ; }, abstract = {Malignant pleural mesothelioma is a fatal malignancy linked to asbestos exposure. The main challenge for mesothelioma treatment is to go beyond the drug resistance, in particular against cisplatin (CDDP), one of the most used chemotherapeutic drug. 3-O-methylfunicone (OMF) is a metabolite produced by the fungus Penicillium pinophilum; its antiproliferative properties have been previously studied in vitro. Particularly, OMF is able to inhibit mesothelioma cell motility. To improve the effects of CDDP by-passing the resistance of mesothelioma cells to this drug, in the present study we investigated the combined treatment of OMF with CDDP respectively in an established mesothelioma cell line (NCI) and primary mesothelioma cells (Mest). As compared to the effect of single treatments, the combination of OMF and CDDP resulted in a stronger inhibition of NCI and Mest cell proliferation. OMF combination with CDDP was also able to affect the migratory ability of NCI and Mest cells by down-regulating αv and β5 expression and reducing metalloproteinase 2 (MMP-2) production. In addition, this association was effective in modulating VEGF gene expression. This finding highlights the possibility to use OMF and CDDP together to regulate angiogenesis and tumour progression in mesothelioma.}, } @article {pmid21656122, year = {2011}, author = {Tomioka, K and Natori, Y and Kumagai, S and Kurumatani, N}, title = {An updated historical cohort mortality study of workers exposed to asbestos in a refitting shipyard, 1947-2007.}, journal = {International archives of occupational and environmental health}, volume = {84}, number = {8}, pages = {959-967}, pmid = {21656122}, issn = {1432-1246}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Asbestosis/*etiology/mortality ; Cause of Death ; Cohort Studies ; Employment/*classification ; Humans ; Japan/epidemiology ; Lung Neoplasms/etiology/mortality ; Male ; Mesothelioma/etiology/mortality ; Middle Aged ; Mortality/*trends ; Occupational Diseases/*etiology/mortality ; Respiration Disorders/etiology/mortality ; Ships ; Survival Rate ; }, abstract = {PURPOSE: To evaluate the long-term health effects of occupational asbestos exposure, an updated historical cohort mortality study of workers at a refitting shipyard was undertaken.

METHODS: The cohort consisted of 249 male ship repair workers (90 laggers, 159 boiler repairers). To determine relative excess mortality, standardized mortality ratios (SMRs) were calculated using mortality rates among the Japanese male population. Mortality follow-up of study subjects was performed for the period from 1947 till the end of 2007.

RESULTS: We identified the vital status of 87 (96.7%) laggers and 150 (94.3%) boiler repairers. Of these, 63 (72.4%) and 95 (63.3%), respectively, died. Laggers, who had handled asbestos materials directly, showed a significantly elevated SMR of 2.64 (95% confidence interval [CI]: 1.06-5.44) for lung cancer and 2.49 (95% CI: 1.36-4.18) for nonmalignant respiratory diseases. Boiler repairers, who had many opportunities for secondary exposure to asbestos and a few for direct exposure, showed no significant elevation in SMR for lung cancer but a significantly elevated SMR of 1.78 (95% CI: 1.06-2.81) for nonmalignant respiratory diseases. In an analysis according to duration of employment, there was a significantly elevated SMR of nonmalignant respiratory diseases in the longer working years group. Among workers from both jobs, no deaths caused by mesothelioma in addition to those in the original study were found and no subject died from larynx cancer.

CONCLUSION: This updated study confirmed a significant excess of asbestos-related mortality from diseases such as lung cancer and nonmalignant respiratory diseases among workers in a refitting shipyard in Japan.}, } @article {pmid21651745, year = {2012}, author = {Brims, FJ and Arif, M and Chauhan, AJ}, title = {Outcomes and complications following medical thoracoscopy.}, journal = {The clinical respiratory journal}, volume = {6}, number = {3}, pages = {144-149}, doi = {10.1111/j.1752-699X.2011.00254.x}, pmid = {21651745}, issn = {1752-699X}, mesh = {Aged ; Asbestosis/epidemiology/*surgery ; Carcinoma, Non-Small-Cell Lung/epidemiology/surgery ; Carcinoma, Small Cell/epidemiology/surgery ; Chest Tubes/statistics & numerical data ; Female ; Humans ; Length of Stay/statistics & numerical data ; Lung Neoplasms/epidemiology/surgery ; Male ; Mesothelioma/epidemiology/surgery ; Morbidity ; Pleural Effusion/epidemiology/*surgery ; Pleural Effusion, Malignant/epidemiology/surgery ; Postoperative Complications/*epidemiology ; Retrospective Studies ; Thoracoscopes ; Thoracoscopy/*adverse effects/instrumentation/statistics & numerical data ; Treatment Outcome ; United Kingdom/epidemiology ; }, abstract = {INTRODUCTION: Thoracoscopy is an invasive procedure that may be performed by physicians for the investigation of exudative pleural effusion using local anaesthesia, conscious sedation and a rigid thoracoscope.

OBJECTIVES:   We sought to evaluate the safety and outcome of thoracoscopy in Portsmouth Hospitals, UK, a dockyard city with high previous asbestos usage.

METHODS: Retrospective casenote, radiology and laboratory result analysis of patients undergoing thoracoscopy in our institution over a 12-month period.

RESULTS: Fifty-seven of 58 casenotes were available for analysis. Median (interquartile range) age was 73.0 (66.5-79.0) years and 44 (77.2%) were male. Median time with chest drain post-procedure was 3.0 (2.0-5.0) days, and length of stay (LOS) was 4.0 (2.0-8.0) days. Malignant histology was reported in 40 (70.2%), with 25 (62.5%) cases of mesothelioma. There were no deaths related to the procedure. Hospital-acquired infection (HAI) occurred in six (10.5%: pneumonia four, empyema two), all had malignancy. The presence of HAI significantly prolonged the LOS 9.0 (7.5-23.5) vs no HAI 4.0 (2.0-7.0) days; P = 0.006). Four patients died within 1 month of the procedure, three had a malignant diagnosis, all had suffered HAI. Trapped lung (persistent hydropneumothorax 5 days post-procedure) occurred in 11 (19.2%), six of whom had benign histology. Performance status (European Cooperative Oncology Group) prior did not differ with reported histological type: benign 2.0 (2.0-2.0), malignant 2.0 (2.0-3.0), P = 0.170.

CONCLUSIONS: Serious complications following thoracoscopy are rare. HAI is associated with malignancy and prolonged hospital stay. Benign histology may still confer significant morbidity.}, } @article {pmid21651743, year = {2012}, author = {Knuuttila, A and Salomaa, ER and Saikkonen, S and Hurme, S and Salo, J}, title = {Pemetrexed in malignant pleural mesothelioma and the clinical outcome.}, journal = {The clinical respiratory journal}, volume = {6}, number = {2}, pages = {96-103}, doi = {10.1111/j.1752-699X.2011.00252.x}, pmid = {21651743}, issn = {1752-699X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/*therapeutic use ; Female ; Finland ; Glutamates/*therapeutic use ; Guanine/*analogs & derivatives/therapeutic use ; Humans ; Male ; Mesothelioma/*drug therapy/mortality/pathology ; Middle Aged ; Pemetrexed ; Pleural Neoplasms/*drug therapy/mortality/pathology ; Retrospective Studies ; Survival Rate ; Treatment Outcome ; }, abstract = {INTRODUCTION: Pemetrexed has emerged as standard chemotherapy for malignant pleural mesothelioma (MPM).

OBJECTIVES: MPMs at two Finnish University Hospitals during 7 years (2000-2006) were reviewed in order to evaluate the treatments, survival and prognostic factors. The results in two periods (before pemetrexed use in 2000-2002 and with pemetrexed in 2003-2006) were compared.

METHODS: Data were collected from the individual patient records retrospectively, and analysed.

RESULTS: Altogether 197 patients were diagnosed with following histologies: 136 (69%) epithelioid, 19 (10%) sarcomatoid, 17 (9%) mixed, 25 (13%) not specified; 141 (72%) patients received treatment (five extrapleural pneumonectomy, 36 pleurectomy/decortication, 126 chemotherapy). Median survival was 12.9 months and the 1-, 2- and 3-year survivals were 51.8%, 21.8% and 12.1%, respectively. Univariate analysis showed no significant difference in survival between the patients diagnosed before or during the pemetrexed era (P = 0.124). The patients receiving pemetrexed or other chemotherapy had median survivals of 16.7 and 15.3 months, respectively. The independent prognostic factors for survival were histology and asbestos exposure. Non-epithelioid histology yielded 17 times higher risk of dying than epithelioid. Asbestos exposure doubled the risk of dying, but only in patients diagnosed in 2003-2006.

CONCLUSIONS: Pemetrexed is beneficial for selected patients, but it has not changed the outcome of the whole MPM population as much as perhaps anticipated. Patient groups with various treatments or symptomatic care only reached survival results comparable to those reported in chemotherapy trials, thus emphasising the need for better subtyping of mesothelioma and individualising the treatment.}, } @article {pmid21647880, year = {2012}, author = {Marinaccio, A and Binazzi, A and Marzio, DD and Scarselli, A and Verardo, M and Mirabelli, D and Gennaro, V and Mensi, C and Riboldi, L and Merler, E and Zotti, RD and Romanelli, A and Chellini, E and Silvestri, S and Pascucci, C and Romeo, E and Menegozzo, S and Musti, M and Cavone, D and Cauzillo, G and Tumino, R and Nicita, C and Melis, M and Iavicoli, S and , }, title = {Pleural malignant mesothelioma epidemic: incidence, modalities of asbestos exposure and occupations involved from the Italian National Register.}, journal = {International journal of cancer}, volume = {130}, number = {9}, pages = {2146-2154}, doi = {10.1002/ijc.26229}, pmid = {21647880}, issn = {1097-0215}, mesh = {Adult ; Age Factors ; Aged ; Asbestos/adverse effects/chemistry ; Epidemics ; Female ; Humans ; Italy/epidemiology ; Male ; Mesothelioma/chemically induced/*epidemiology/*pathology ; Middle Aged ; Occupational Diseases/chemically induced ; Occupational Exposure/adverse effects ; Pleural Neoplasms/chemically induced/*epidemiology/*pathology ; Population Surveillance ; }, abstract = {Due to the large scale use of asbestos (more than 3.5 million tons produced or imported until its definitive banning in 1992), a specific national surveillance system of mesothelioma incident cases is active in Italy, with direct and individual anamnestic etiological investigation. In the period between 1993 and 2004, a case-list of 8,868 pleural MM was recorded by the Italian National Register (ReNaM) and the modalities of exposure to asbestos fibres have been investigated for 6,603 of them. Standardized incidence rates are 3.49 (per 100,000 inhabitants) for men and 1.25 for women, with a wide regional variability. Occupational asbestos exposure was in 69.3% of interviewed subjects (N = 4,577 cases), while 4.4% was due to cohabitation with someone (generally, the husband) occupationally exposed, 4.7% by environmental exposure from living near a contamination source and 1.6% during a leisure activity. In the male group, 81.5% of interviewed subjects exhibit an occupational exposure. In the exposed workers, the median year of first exposure was 1957, and mean latency was 43.7 years. The analysis of exposures by industrial sector focuses on a decreasing trend for those traditionally signaled as "at risk" (asbestos-cement industry, shipbuilding and repair and railway carriages maintenance) and an increasing trend for the building construction sector. The systematic mesothelioma surveillance system is relevant for the prevention of the disease and for supporting an efficient compensation system. The existing experience on all-too-predictable asbestos effects should be transferred to developing countries where asbestos use is spreading.}, } @article {pmid21645609, year = {2011}, author = {Martinotti, S and Ranzato, E and Burlando, B}, title = {In vitro screening of synergistic ascorbate-drug combinations for the treatment of malignant mesothelioma.}, journal = {Toxicology in vitro : an international journal published in association with BIBRA}, volume = {25}, number = {8}, pages = {1568-1574}, doi = {10.1016/j.tiv.2011.05.023}, pmid = {21645609}, issn = {1879-3177}, mesh = {Antineoplastic Agents/*pharmacology ; Antineoplastic Combined Chemotherapy Protocols/*pharmacology ; Ascorbic Acid/administration & dosage ; Catechin/administration & dosage/analogs & derivatives ; Cell Line, Tumor ; Cell Proliferation/*drug effects ; Cell Survival/drug effects ; Coloring Agents/metabolism ; Deoxycytidine/administration & dosage/analogs & derivatives ; Drug Synergism ; Humans ; L-Lactate Dehydrogenase/metabolism ; Lung Neoplasms/*drug therapy/metabolism ; Mesothelioma/*drug therapy/metabolism ; Neutral Red/metabolism ; Gemcitabine ; }, abstract = {Malignant mesothelioma (MMe) is a lethal tumor arising from the mesothelium of serous cavities as a result of exposure to asbestos. Current clinical standards consist of combined treatments, but an effective therapy has not been established yet and there is an urgent need for new curative approaches. Ascorbate is a nutrient that is also known as a remedy in the treatment of cancer. In the present study, we have tested the cytotoxicity of ascorbate to MMe cells in combination with drugs used in MMe therapy, such as cisplatin, etoposide, gemcitabine, imatinib, paclitaxel, and raltitrexed, as well as with promising antitumor compounds like taurolidine, α-tocopherol succinate, and epigallocatechin-3-gallate (EGCG). Dose-response curves obtained for each compound by applying the neutral red uptake (NRU) assay to MMe cells growing in vitro, allowed to obtain IC50 values for each compound used singularly. Thereafter, NRU data obtained from each ascorbate/drug combination were analyzed through Tallarida's isobolograms at the IC50 level (Tallarida, 2000), revealing synergistic interactions for ascorbate/gemcitabine and ascorbate/EGCG. These results were further confirmed through comparisons between theoretical additivity IC50 and observed IC50 from fixed-ratio dose-response curves, and over a broad range of IC levels, by using Chou and Talalay's combination index (Chou and Talalay, 1984). Synergistic interactions were also shown by examining apoptosis and necrosis rates, using the caspase 3 and lactic dehydrogenase assays, respectively. Hence, data indicate that ascorbate/gemcitabine and ascorbate/EGCG affect synergistically the viability of MMe cells and suggest their possible use in the clinical treatment of this problematic cancer.}, } @article {pmid21642872, year = {2011}, author = {Cristaudo, A and Bonotti, A and Simonini, S and Vivaldi, A and Guglielmi, G and Ambrosino, N and Chella, A and Lucchi, M and Mussi, A and Foddis, R}, title = {Combined serum mesothelin and plasma osteopontin measurements in malignant pleural mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {6}, number = {9}, pages = {1587-1593}, doi = {10.1097/JTO.0b013e31821e1c08}, pmid = {21642872}, issn = {1556-1380}, mesh = {Biomarkers, Tumor/*blood ; Case-Control Studies ; Enzyme-Linked Immunosorbent Assay ; Female ; GPI-Linked Proteins/*blood ; Humans ; Male ; Mesothelin ; Mesothelioma/blood/*diagnosis ; Middle Aged ; Osteopontin/*blood ; Pleural Neoplasms/blood/*diagnosis ; Prognosis ; Sensitivity and Specificity ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is a lethal tumor related to asbestos exposure. At present, the only instruments for screening and diagnosis are based on radiological tests, posing evident economic and radio-protectionist problems. Some authors are evaluating biological indicators, such as plasma osteopontin (pOPN) and serum soluble mesothelin-related peptides (SMRP). This study aimed to evaluate whether a combination of these two markers could increase sensitivity and specificity in diagnosis of epithelioid MPM.

METHODS: We enrolled 93 healthy subjects, 111 individuals with benign respiratory disease (BRD), and 31 patients with MPM, histologically and/or cytologically confirmed. SMRP and pOPN levels were determined using commercially available enzyme-linked immunosorbent assay kits. Though a logistic regression analysis, SMRP and pOPN were combined and translated into a new index, called "combined risk index."

RESULTS: Differences in both SMRP and pOPN mean values between epithelial MPM patients and healthy subjects or BRD patients were statistically significant (p < 0.0001), whereas there was no difference in SMRP and pOPN mean values between healthy subjects and BRD patients. The performance in MPM diagnosis resulted improved by the combination of the two markers. The results of our study should be confirmed by a larger scale and, possibly, a multicenter study, which could better take into consideration the influence of some possible confounding factors such as glomerular filtration rate and other blood parameters.

CONCLUSIONS: We combined SMRP and pOPN dosages to increase diagnostic accuracy. This study showed for the first time that combined SMRP and pOPN measurements can increase both sensitivity and specificity in terms of combined risk index.}, } @article {pmid21641383, year = {2011}, author = {Murphy, FA and Poland, CA and Duffin, R and Al-Jamal, KT and Ali-Boucetta, H and Nunes, A and Byrne, F and Prina-Mello, A and Volkov, Y and Li, S and Mather, SJ and Bianco, A and Prato, M and Macnee, W and Wallace, WA and Kostarelos, K and Donaldson, K}, title = {Length-dependent retention of carbon nanotubes in the pleural space of mice initiates sustained inflammation and progressive fibrosis on the parietal pleura.}, journal = {The American journal of pathology}, volume = {178}, number = {6}, pages = {2587-2600}, pmid = {21641383}, issn = {1525-2191}, mesh = {Animals ; Cell Proliferation ; *Disease Progression ; Epithelium/pathology ; Fibrosis ; Inflammation/*complications/*pathology ; Lymph Nodes/pathology ; Mediastinum/pathology ; Mice ; Nanotubes, Carbon/*chemistry/ultrastructure ; Nanowires/ultrastructure ; Particle Size ; Pleura/*pathology/ultrastructure ; Pleural Cavity/*pathology/ultrastructure ; Time Factors ; Tomography, Emission-Computed, Single-Photon ; Tomography, X-Ray Computed ; }, abstract = {The fibrous shape of carbon nanotubes (CNTs) raises concern that they may pose an asbestos-like inhalation hazard, leading to the development of diseases, especially mesothelioma. Direct instillation of long and short CNTs into the pleural cavity, the site of mesothelioma development, produced asbestos-like length-dependent responses. The response to long CNTs and long asbestos was characterized by acute inflammation, leading to progressive fibrosis on the parietal pleura, where stomata of strictly defined size limit the egress of long, but not short, fibers. This was confirmed by demonstrating clearance of short, but not long, CNT and nickel nanowires and by visualizing the migration of short CNTs from the pleural space by single-photon emission computed tomographic imaging. Our data confirm the hypothesis that, although a proportion of all deposited particles passes through the pleura, the pathogenicity of long CNTs and other fibers arises as a result of length-dependent retention at the stomata on the parietal pleura.}, } @article {pmid21641092, year = {2011}, author = {Orcajo Rincón, J and Alonso Farto, JC and Rotger Regi, A and Hernández Pérez, R and Hualde, AM and Pérez Aradas, V}, title = {[Usefulness of 18F-FDG PET-CT in the presurgical assessment of malignant pleural mesothelioma treated with neoadjuvant chemotherapy].}, journal = {Revista espanola de medicina nuclear}, volume = {30}, number = {5}, pages = {307-310}, doi = {10.1016/j.remn.2010.08.008}, pmid = {21641092}, issn = {1578-200X}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Cisplatin/administration & dosage ; Combined Modality Therapy ; *Fluorine Radioisotopes ; *Fluorodeoxyglucose F18 ; Glutamates/administration & dosage ; Guanine/administration & dosage/analogs & derivatives ; Humans ; Lymphatic Metastasis ; Male ; Mesothelioma/*diagnostic imaging/drug therapy/secondary/surgery ; Middle Aged ; *Multimodal Imaging ; *Neoadjuvant Therapy ; Pemetrexed ; Pleural Neoplasms/*diagnostic imaging/drug therapy/surgery ; *Positron-Emission Tomography ; Preoperative Care ; *Radiopharmaceuticals ; *Tomography, X-Ray Computed ; Tumor Burden ; }, abstract = {Malignant pleural mesothelioma is a relatively rare, but highly aggressive, tumor, associated to exposure to asbestos, with a life expectancy between 9 and 17 months. Chest pain and dyspnea are the most frequent symptoms. The most commonly used therapy is surgery accompanied by chemotherapy. Preoperative assessment, after chemotherapy, has been done using magnetic resonance imaging and computed tomography (CT). However, these techniques cannot predict early response to therapy, because of the slow structural change of the tumor. The aim of this case report is to review and learn about the growing use of PET-CT imaging with (18)F-FDG in the preoperative staging of malignant pleural mesothelioma and its influence in selecting the most appropriate type of surgery.}, } @article {pmid21630296, year = {2011}, author = {Geyer, SJ}, title = {The need for pathological confirmation of the diagnosis of peritoneal malignant mesothelioma.}, journal = {American journal of industrial medicine}, volume = {54}, number = {8}, pages = {646}, doi = {10.1002/ajim.20959}, pmid = {21630296}, issn = {1097-0274}, mesh = {Asbestos, Serpentine/*toxicity ; Humans ; Male ; Mesothelioma/*epidemiology ; Occupational Diseases/*epidemiology ; Occupational Exposure/*adverse effects ; Peritoneal Neoplasms/*epidemiology ; }, } @article {pmid21621109, year = {2011}, author = {Frija, J}, title = {[The current asbestos scandal].}, journal = {Journal de radiologie}, volume = {92}, number = {5}, pages = {428-430}, doi = {10.1016/j.jradio.2011.03.019}, pmid = {21621109}, issn = {1773-0384}, mesh = {Asbestos/*toxicity ; France ; Humans ; Mesothelioma/*etiology ; Occupational Exposure/adverse effects ; Pleural Neoplasms/*etiology ; Politics ; }, } @article {pmid21621102, year = {2011}, author = {Laurent, F}, title = {[Imaging and postoccupational surveillance after exposure to asbestos: new recommendations].}, journal = {Journal de radiologie}, volume = {92}, number = {5}, pages = {367-368}, doi = {10.1016/j.jradio.2011.05.003}, pmid = {21621102}, issn = {1773-0384}, mesh = {Asbestos/*toxicity ; Asbestosis/*diagnosis/*diagnostic imaging ; Humans ; Mesothelioma/*etiology ; Occupational Diseases/*diagnosis ; *Occupational Exposure ; Pleural Neoplasms/*etiology ; Radiography, Thoracic/*methods ; Tomography, X-Ray Computed/*methods ; }, } @article {pmid21620489, year = {2011}, author = {Favoni, RE and Florio, T}, title = {Combined chemotherapy with cytotoxic and targeted compounds for the management of human malignant pleural mesothelioma.}, journal = {Trends in pharmacological sciences}, volume = {32}, number = {8}, pages = {463-479}, doi = {10.1016/j.tips.2011.03.011}, pmid = {21620489}, issn = {1873-3735}, mesh = {Antineoplastic Agents/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Asbestos ; Cisplatin/therapeutic use ; Clinical Trials as Topic ; Glutamates/therapeutic use ; Guanine/analogs & derivatives/therapeutic use ; Humans ; Medical Oncology/methods ; Mesothelioma/physiopathology/*therapy ; Models, Biological ; Molecular Targeted Therapy ; Palliative Care ; Pemetrexed ; Pleural Neoplasms/physiopathology/*therapy ; Prognosis ; Protein Kinase Inhibitors/therapeutic use ; Proto-Oncogene Mas ; Radiotherapy ; Signal Transduction ; Treatment Outcome ; }, abstract = {Human malignant pleural mesothelioma (hMPM) is an aggressive asbestos-associated cancer, the incidence of which is increasing and which, despite progress in diagnosis and therapy, continues to have a poor prognosis. Asbestos fibers induce aberrant cell signaling, leading to proto-oncogene activation and chemoresistance. In this review, we discuss the evolution of pharmacological management of hMPM up to the most recent advances. Monotherapy with single cytotoxic drugs achieves modest objective response rates, seldom reaching 30%. However, combination regimens using novel drugs and standard molecules are showing gradually improving responses and clinical benefits. Phase II/III studies have identified pemetrexed, a multitarget folate pathway inhibitor in combination with platinum derivatives, and the cisplatin/gemcitabine association as front-line chemotherapy for hMPM. Detailed knowledge of molecular mechanisms of signal transduction and neoangiogenesis in hMPM should aid in the design and screening of other promising compounds such as more efficacious receptor tyrosine kinase inhibitors.}, } @article {pmid21620418, year = {2011}, author = {Watzka, SB and Posch, F and Pass, HI and Huflejt, M and Bernhard, D and Hannigan, GE and Müller, MR}, title = {Detection of integrin-linked kinase in the serum of patients with malignant pleural mesothelioma.}, journal = {The Journal of thoracic and cardiovascular surgery}, volume = {142}, number = {2}, pages = {384-389}, doi = {10.1016/j.jtcvs.2011.04.034}, pmid = {21620418}, issn = {1097-685X}, mesh = {Aged ; Biomarkers/blood ; Cell Transformation, Neoplastic ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Male ; Mesothelioma/*blood/diagnosis/enzymology ; Middle Aged ; Pleural Neoplasms/*blood/diagnosis/enzymology ; Prognosis ; Protein Serine-Threonine Kinases/*blood ; Sensitivity and Specificity ; }, abstract = {OBJECTIVE: Integrin-linked kinase, which is relevant to neoplastic transformation, is highly expressed in malignant pleural mesothelioma. Recently, detection of integrin-linked kinase in serum of patients with ovarian cancer has been reported. This study asks whether integrin-linked kinase can also be detected in serum of patients with malignant pleural mesothelioma and whether serum level has diagnostic or prognostic relevance for that disease.

METHODS: A sandwich enzyme-linked immunosorbent assay was designed to detect integrin-linked kinase and applied to serum samples from 46 patients with malignant pleural mesothelioma, 98 patients with other malignant chest disease, and 23 patients with benign chest disease. Integrin-linked kinase serum concentration and clinical data were correlated statistically.

RESULTS: Median serum integrin-linked kinase concentration was significantly higher in malignant pleural mesothelioma (8.89 ng/mL) than in other malignant chest disease (0.66 ng/mL) or benign chest disease (0.78 ng/mL, P < .001). There was no relevant correlation of serum integrin-linked kinase with cell lysis parameters (R(2) < 0.1). Serum integrin-linked kinase concentration greater than 2.48 ng/mL had diagnostic sensitivity of 80%, specificity of 95%, positive predictive value of 85.7%, negative predictive value of 92.7%, and overall accuracy of 91% for distinction between malignant pleural mesothelioma and other diseases. Serum integrin-linked kinase concentration in malignant pleural mesothelioma was independent of histologic subtype or asbestos exposure. There was no statistically significant impact of serum integrin-linked kinase concentration on prognosis.

CONCLUSIONS: Integrin-linked kinase can be detected in serum of patients with malignant pleural mesothelioma and may be a diagnostic marker for the disease.}, } @article {pmid21617708, year = {2011}, author = {Bianchi, C and Bianchi, T and Bucconi, S}, title = {Malignant mesothelioma of the pleura in nonagenarian patients.}, journal = {Tumori}, volume = {97}, number = {2}, pages = {156-159}, doi = {10.1177/030089161109700204}, pmid = {21617708}, issn = {0300-8916}, mesh = {Aged, 80 and over ; Asbestos/*adverse effects ; Autopsy ; Female ; Humans ; Italy/epidemiology ; Male ; Mesothelioma/diagnosis/*epidemiology/*etiology/immunology ; Occupational Diseases/diagnosis/*epidemiology/etiology/immunology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/diagnosis/*epidemiology/*etiology/immunology ; Risk Factors ; Time Factors ; }, abstract = {AIMS AND BACKGROUND: Malignant mesothelioma developing at very old ages is a rare event. The reasons for such late development were investigated.

METHODS: A series of 811 malignant mesothelioma of the pleura, diagnosed at the Trieste and Monfalcone Hospitals, in northeastern Italy, in the period 1968-2008 were reviewed. Eight cases regarding patients aged 90 years or more were selected. In such cases, occupational histories were re-examined, and additional data could be obtained from the patients' relatives. Routine lung sections obtained at necropsy were examined for asbestos bodies. In 2 cases, asbestos bodies had been isolated after chemical digestion of lung tissue.

RESULTS: The group included 7 men and one woman, aged between 90 and 93 years. All 8 patients had long-term histories of occupational exposure to asbestos, mostly in shipyards. Latency periods, elapsed between first exposure to asbestos and tumor manifestation, ranged between 64 and 75 years. Asbestos bodies were found on routine lung sections in 6 cases. Isolation of lung asbestos bodies showed 72,000 bodies per gram of dried tissue in a 90-year-old man, who had worked in the shipyards for 34 years, and 150 bodies per gram in a 93-year-old woman, who had worked in the shipyards for 23 years.

CONCLUSIONS: In this group of cases, the late development of mesothelioma can not be attributed to mild exposure to asbestos or to unusually late exposures. Very long latency periods even in people heavily exposed suggest an individual resistance to the oncogenic effects of asbestos.}, } @article {pmid21615608, year = {2011}, author = {Sekido, Y}, title = {Inactivation of Merlin in malignant mesothelioma cells and the Hippo signaling cascade dysregulation.}, journal = {Pathology international}, volume = {61}, number = {6}, pages = {331-344}, doi = {10.1111/j.1440-1827.2011.02666.x}, pmid = {21615608}, issn = {1440-1827}, mesh = {Animals ; Cell Line, Tumor ; Chromosomes, Human, Pair 22 ; Disease Models, Animal ; Drosophila ; Drosophila Proteins/genetics/physiology ; Genes, Tumor Suppressor ; Humans ; Intracellular Signaling Peptides and Proteins/genetics/metabolism/*physiology ; Mesothelioma/*genetics/pathology ; Mutation ; Neurofibromin 2/chemistry/genetics/*physiology ; Phosphorylation ; Pleural Neoplasms/*genetics/pathology ; Protein Serine-Threonine Kinases/genetics/physiology ; Signal Transduction/*physiology ; Tumor Suppressor Proteins/genetics ; }, abstract = {Malignant mesothelioma (MM) is an aggressive tumor arising primarily from pleural or peritoneal cavities, which is caused by asbestos exposure after long latency. One of the most frequently mutated genes detected in MM cells is the neurofibromatosis type 2 (NF2) tumor suppressor gene which is located at chromosome 22q12. The NF2 gene encodes Merlin, an ERM (Ezrin/Radixin/Moesin) protein. The underphosphorylated form of Merlin is active and acts as a tumor suppressor by regulating several distinct cellular signaling pathways. One of the downstream pathways regulated by Merlin is the Hippo signaling pathway, which is conserved from Drosophila to mammalian cells and plays important roles in organ size control and cancer development. Recent studies have identified alterations of the components in the Hippo signaling cascade in MM cells, including overexpression of Yes-associated protein (YAP) and inactivation of large tumor suppressor homolog 2 (LATS2). Dysregulation of the Merlin-Hippo signaling cascade is one of the frequent and key events of MM cell development and/or progression. Thus, a strategy to normalize this signaling cascade may be the rationale for developing a new target therapy against MM.}, } @article {pmid21610219, year = {2011}, author = {Reid, A and de Klerk, N and Musk, AW}, title = {Does exposure to asbestos cause ovarian cancer? A systematic literature review and meta-analysis.}, journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology}, volume = {20}, number = {7}, pages = {1287-1295}, doi = {10.1158/1055-9965.EPI-10-1302}, pmid = {21610219}, issn = {1538-7755}, mesh = {Asbestos/*toxicity ; Case-Control Studies ; Cohort Studies ; Female ; Humans ; Ovarian Neoplasms/*chemically induced ; }, abstract = {INTRODUCTION: The asbestos and ovarian cancer relationship is not well understood because of small numbers of women exposed to asbestos, small numbers of cases, and misclassification of peritoneal mesothelioma as ovarian cancer on death certificates. The aim of this study was to conduct a meta-analysis to quantify the evidence that exposure to asbestos causes ovarian cancer.

METHODS: Fourteen cohort and two case-control studies were identified in Medline searches from 1950 to 2008.

RESULTS: Statistically significant excess mortality was reported in four of the cohort studies, all of which determined their outcomes from the death certificate. Peritoneal mesotheliomas were reported in these studies, two of which reexamined pathology specimens and reported disease misclassification. Exposure-response relationships were inconsistent. When all studies were included in a meta-analysis, the effect size was 1.75 (95% CI, 1.45-2.10) attenuating to 1.29 (95% CI, 0.97-1.73) in studies with confirmed ovarian cancers.

CONCLUSION: Taken without further analysis, women thought to have ovarian cancer had an increased rate in the meta-analysis if reporting having been exposed to asbestos, compared with reference populations. This result may have occurred because of disease misclassification.}, } @article {pmid21606998, year = {2011}, author = {Langård, S}, title = {[When is cancer work-connected?].}, journal = {Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke}, volume = {131}, number = {9-10}, pages = {965-967}, doi = {10.4045/tidsskr.10.1027}, pmid = {21606998}, issn = {0807-7096}, mesh = {Asbestos/*adverse effects ; Carcinogens ; Gastrointestinal Neoplasms/chemically induced ; Humans ; Lung Neoplasms/chemically induced ; Mesothelioma/chemically induced ; Neoplasms/*chemically induced ; Norway ; *Occupational Diseases/diagnosis/etiology ; Occupational Exposure/*adverse effects ; Risk Factors ; *Workers' Compensation ; }, } @article {pmid21600703, year = {2011}, author = {Nagata, S and Tomoeda, M and Kubo, C and Yoshizawa, H and Yuki, M and Kitamura, M and Takenaka, A and Nakanishi, K and Yagi, T and Imamura, F and Tomita, Y}, title = {Malignant mesothelioma of the peritoneum invading the liver and mimicking metastatic carcinoma: a case report.}, journal = {Pathology, research and practice}, volume = {207}, number = {6}, pages = {395-398}, doi = {10.1016/j.prp.2011.04.004}, pmid = {21600703}, issn = {1618-0631}, mesh = {Biopsy ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; Liver/*pathology ; Liver Neoplasms/*secondary ; Mesothelioma/*pathology ; Middle Aged ; Neoplasm Invasiveness ; Peritoneal Neoplasms/*pathology ; Predictive Value of Tests ; Tomography, X-Ray Computed ; }, abstract = {We present a case of malignant mesothelioma of the peritoneum with massive direct invasion to the liver in a 58-year-old Japanese woman. She had no history of asbestos exposure or other malignancies. Abdominal computed tomography revealed one 8-cm intrahepatic mass adjacent to the abdominal wall with peritoneal thickening, multiple smaller nodules in the peritoneal cavity, and intra-abdominal lymphadenopathy. Liver biopsy showed a small cluster of atypical cells similar to epithelial neoplasm, which formed a tubulopapillary structure. The tumor cells were positive for calretinin with strong nuclear and cytoplasmic expression together with podoplanin (D2-40) and some cytokeratins, but were negative for hepatocyte paraffin 1 and other adenocarcinoma markers. We confirmed a diffuse peritoneal mesothelioma with direct invasion to the liver. Liver masses with other peritoneal nodules are mostly encountered as metastatic diseases. However, the possibility of mesothelioma should be considered, even in women without an apparent history of asbestos exposure.}, } @article {pmid21594647, year = {2011}, author = {Wang, Y and Rishi, AK and Wu, W and Polin, L and Sharma, S and Levi, E and Albelda, S and Pass, HI and Wali, A}, title = {Curcumin suppresses growth of mesothelioma cells in vitro and in vivo, in part, by stimulating apoptosis.}, journal = {Molecular and cellular biochemistry}, volume = {357}, number = {1-2}, pages = {83-94}, pmid = {21594647}, issn = {1573-4919}, support = {P30 CA022453/CA/NCI NIH HHS/United States ; }, mesh = {Adaptor Proteins, Signal Transducing ; Animals ; Antineoplastic Agents/*pharmacology ; Apoptosis/*drug effects ; Apoptosis Regulatory Proteins ; Carrier Proteins/drug effects ; Caspases/drug effects ; Cell Cycle Proteins ; Cell Line, Tumor ; Cell Proliferation/*drug effects ; Curcumin/*pharmacology ; Dose-Response Relationship, Drug ; Gene Expression Regulation ; Humans ; Intracellular Signaling Peptides and Proteins/drug effects ; Mesothelioma/*metabolism ; Mice ; Neoplasm Proteins/drug effects ; Pleural Neoplasms/*metabolism ; Sulfotransferases/drug effects ; bcl-2-Associated X Protein/drug effects ; p38 Mitogen-Activated Protein Kinases/drug effects ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive, asbestos-related malignancy of the thoracic pleura. Although, platinum-based agents are the first line of therapy, there is an urgent need for second-line therapies to treat the drug-resistant MPM. Cell cycle as well as apoptosis pathways are frequently altered in MPM and thus remain attractive targets for intervention strategies. Curcumin, the major component in the spice turmeric, alone or in combination with other chemotherapeutics has been under investigation for a number of cancers. In this study, we investigated the biological and molecular responses of MPM cells to curcumin treatments and the mechanisms involved. Flow-cytometric analyses coupled with western immunoblotting and gene-array analyses were conducted to determine mechanisms of curcumin-dependent growth suppression of human (H2373, H2452, H2461, and H226) and murine (AB12) MPM cells. Curcumin inhibited MPM cell growth in a dose- and time-dependent manner while pretreatment of MPM cells with curcumin enhanced cisplatin efficacy. Curcumin activated the stress-activated p38 kinase, caspases 9 and 3, caused elevated levels of proapoptotic proteins Bax, stimulated PARP cleavage, and apoptosis. In addition, curcumin treatments stimulated expression of novel transducers of cell growth suppression such as CARP-1, XAF1, and SULF1 proteins. Oral administration of curcumin inhibited growth of murine MPM cell-derived tumors in vivo in part by stimulating apoptosis. Thus, curcumin targets cell cycle and promotes apoptosis to suppress MPM growth in vitro and in vivo. Our studies provide a proof-of-principle rationale for further in-depth analysis of MPM growth suppression mechanisms and their future exploitation in effective management of resistant MPM.}, } @article {pmid21574260, year = {2011}, author = {Ustun, H and Astarci, HM and Sungu, N and Ozdemir, A and Ekinci, C}, title = {Primary malignant deciduoid peritoneal mesothelioma: a report of the cytohistological and immunohistochemical appearances.}, journal = {Diagnostic cytopathology}, volume = {39}, number = {6}, pages = {402-408}, doi = {10.1002/dc.21400}, pmid = {21574260}, issn = {1097-0339}, mesh = {Biomarkers, Tumor/*metabolism ; Calbindin 2 ; Cell Size ; Female ; Humans ; Keratin-5/metabolism ; Keratin-6/metabolism ; Mesothelioma/*diagnosis/metabolism/surgery ; Middle Aged ; Peritoneal Neoplasms/*diagnosis/metabolism/surgery ; S100 Calcium Binding Protein G/metabolism ; }, abstract = {Malignant deciduoid mesothelioma (MDM) is a rare variant of epithelioid mesothelioma. This type of tumor might be associated with the asbestos exposure and carries a poor prognosis in general. MDM was first described by Nascimento et al. in 1994 in a peritoneal lesion of a young woman. And its diagnosis is frequently mistaken with florid mesothelial hyperplasia and peritoneal deciduosis. There are 44 MDM cases reported in the literature up today. A 59-year-old woman patient referred to our clinic was identified with an abdominal mass. Computed tomography of whole abdomen of the patient showed a mass with the widest transverse dimension of 65 × 60 mm at abdominal bifurcation in the mesenteric region. The patient was diagnosed with MDM after the cytopathological examination of the fine needle aspiration biopsy performed from the mass. Consequently, she received a total mass excision and right hemicolectomy under general anesthesia. The cytomorphological appearance of the ascitic fluid is detailed for the first time by Gillespie et al. and is described only in two manuscripts. In the present study, we aimed to report a case of a 59-year-old woman since she was diagnosed with MDM and because her cytological findings were further supported by histomorphological and immunohistochemical evaluations of the operation material obtained from the patient.}, } @article {pmid21574151, year = {2011}, author = {Cristaudo, A and Foddis, R and Bonotti, A and Simonini, S and Vivaldi, A and Guglielmi, G and Bruno, R and Gemignani, F and Landi, S}, title = {Two novel polymorphisms in 5' flanking region of the mesothelin gene are associated with soluble mesothelin-related peptide (SMRP) levels.}, journal = {The International journal of biological markers}, volume = {26}, number = {2}, pages = {117-123}, doi = {10.5301/JBM.2011.8332}, pmid = {21574151}, issn = {1724-6008}, mesh = {5' Flanking Region/genetics ; Asbestos/*toxicity ; Biomarkers, Tumor/*blood/*genetics ; GPI-Linked Proteins/*blood/*genetics ; Gene Frequency ; Humans ; Male ; Mesothelin ; Mesothelioma/*blood/chemically induced ; Middle Aged ; Occupational Diseases/*blood/chemically induced ; *Occupational Exposure ; Peptides/blood ; Pleural Neoplasms/*blood/chemically induced ; Polymorphism, Genetic ; Promoter Regions, Genetic ; }, abstract = {BACKGROUND AND AIMS: Increased concentrations of soluble mesothelin-related peptides (SMRP) have been found in sera of patients with malignant pleural mesothelioma (MPM) even if a relatively high rate of false positives has hampered their clinical use as a tumor marker. Individual SMRP levels could be affected by polymorphic elements. The aim of this study was to investigate the association between single nucleotide polymorphisms within the promoter-5'UTR regions and SMRP levels in healthy asbestos-exposed individuals and patients suffering from MPM.?

METHODS: The promoter-5'UTR regions of the mesothelin gene were genotyped in 59 healthy asbestos-exposed subjects and 27 MPM patients. SMRP levels were measured using a commercially available ELISA kit.?

RESULTS: Two novel polymorphisms, an A>C variant (called New1) and a C>T variant (called New2), were identified. In healthy subjects, high SMRP levels were associated with the C-variant of New1, with an average 1.62-fold increase compared with AA homozygotes (p<0.0001). Most of the C-allele carriers had SMRP levels above the threshold of 1.00 nM. We set two different SMRP cutoffs on the basis of the combined New1+New2 genotypes.?

CONCLUSIONS: New1-New2 genotypes could be employed as markers for setting individualized and appropriate thresholds of "normality" when SMRP is used in surveillance programs of asbestos-exposed people.}, } @article {pmid21573909, year = {2011}, author = {Raja, S and Murthy, SC and Mason, DP}, title = {Malignant pleural mesothelioma.}, journal = {Current oncology reports}, volume = {13}, number = {4}, pages = {259-264}, pmid = {21573909}, issn = {1534-6269}, mesh = {Asbestos/adverse effects ; Humans ; Lung/pathology ; *Mesothelioma/diagnosis/drug therapy/pathology/surgery ; Neoplasm Staging ; Pleura/pathology ; *Pleural Neoplasms/diagnosis/drug therapy/pathology/surgery ; }, abstract = {Malignant pleural mesothelioma (MPM) is a relatively rare thoracic malignancy accounting for about 2000-3000 new cases per year. This cancer has been increasing in incidence and is strongly associated with asbestos exposure. Also, it is characterized by insidious growth and clinical presentation at an advanced stage of disease. In the past, the treatment of this disease was limited to marginally effective chemotherapy and morbid surgery. This review explores the clinical presentation of MPM, its diagnostic approach and the relevant and recent studies that define the role of chemotherapy, radiation, and various surgical options. Currently, even with aggressive surgical interventions and multimodality strategies, cure remains elusive, although life prolongation has been achieved. Additionally, promising new therapies and interventions that are currently being studied are introduced in this review.}, } @article {pmid21570478, year = {2011}, author = {Wang, H and Gillis, A and Zhao, C and Lee, E and Wu, J and Zhang, F and Ye, F and Zhang, DY}, title = {Crocidolite asbestos-induced signal pathway dysregulation in mesothelial cells.}, journal = {Mutation research}, volume = {723}, number = {2}, pages = {171-176}, doi = {10.1016/j.mrgentox.2011.04.008}, pmid = {21570478}, issn = {0027-5107}, mesh = {Asbestos, Crocidolite/*pharmacology ; Cell Line ; Epithelial Cells/drug effects/*metabolism ; Gene Expression Regulation ; Humans ; Mesothelioma/*metabolism ; Phosphoproteins/*metabolism ; Proteins/*metabolism ; Signal Transduction/drug effects ; }, abstract = {BACKGROUND: Malignant mesothelioma is a rare cancer caused by exposure to asbestos. Current therapies have limited efficacy and the prognosis is dismal. A better understanding of the underlying mechanism of asbestos-induced malignant transformation will help to identify molecular markers that can be used for diagnosis, prognosis or therapeutic targets.

OBJECTIVES: The objectives of this study are (1) to identify altered levels of proteins and phosphoproteins and (2) to establish the interactive network among those proteins in crocidolite-treated benign mesothelial cells and in malignant mesothelial cells.

METHODS: Total cellular proteins were extracted from benign mesothelial cells, crocidolite-treated mesothelial cells and malignant mesothelial cells. The expression levels of 112 proteins and phosphoproteins were analyzed using a multiplex immunoblot-based assay followed by computational analysis (Protein Pathway Array).

RESULTS: A total of 16 proteins/phosphoproteins (7 down-regulated and 9 up-regulated) were altered after exposure of benign mesothelial cells to crocidolite asbestos and the majority of them are involved in DNA damage repair and cell cycle regulation. In malignant mesothelial cells, 21 proteins/phosphoproteins (5 down-regulated and 16 up-regulated) were dysregulated and majority of them are involved in EGFR/ERK and PI3K/Akt pathways. Within the regulatory network affected by crocidolite, p53 and NF-κB complex are the most important regulators. There was substantial overlap in the regulatory networks between the asbestos-treated cells and malignant mesothelial cells.

CONCLUSIONS: Asbestos exposure has extensive effects on regulatory pathways and networks. These altered proteins may be used in the future to identify those with a high risk for developing malignant mesothelioma and as targets for preventing this deadly malignancy.}, } @article {pmid21561883, year = {2011}, author = {Adami, HO and Berry, SC and Breckenridge, CB and Smith, LL and Swenberg, JA and Trichopoulos, D and Weiss, NS and Pastoor, TP}, title = {Toxicology and epidemiology: improving the science with a framework for combining toxicological and epidemiological evidence to establish causal inference.}, journal = {Toxicological sciences : an official journal of the Society of Toxicology}, volume = {122}, number = {2}, pages = {223-234}, pmid = {21561883}, issn = {1096-0929}, support = {P30 ES010126/ES/NIEHS NIH HHS/United States ; P42 ES005948/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; *Causality ; *Epidemiology ; Guidelines as Topic ; Humans ; Toxicity Tests ; *Toxicology ; }, abstract = {Historically, toxicology has played a significant role in verifying conclusions drawn on the basis of epidemiological findings. Agents that were suggested to have a role in human diseases have been tested in animals to firmly establish a causative link. Bacterial pathogens are perhaps the oldest examples, and tobacco smoke and lung cancer and asbestos and mesothelioma provide two more recent examples. With the advent of toxicity testing guidelines and protocols, toxicology took on a role that was intended to anticipate or predict potential adverse effects in humans, and epidemiology, in many cases, served a role in verifying or negating these toxicological predictions. The coupled role of epidemiology and toxicology in discerning human health effects by environmental agents is obvious, but there is currently no systematic and transparent way to bring the data and analysis of the two disciplines together in a way that provides a unified view on an adverse causal relationship between an agent and a disease. In working to advance the interaction between the fields of toxicology and epidemiology, we propose here a five-step "Epid-Tox" process that would focus on: (1) collection of all relevant studies, (2) assessment of their quality, (3) evaluation of the weight of evidence, (4) assignment of a scalable conclusion, and (5) placement on a causal relationship grid. The causal relationship grid provides a clear view of how epidemiological and toxicological data intersect, permits straightforward conclusions with regard to a causal relationship between agent and effect, and can show how additional data can influence conclusions of causality.}, } @article {pmid21329571, year = {2011}, author = {Pedata, P and Feola, D and Laieta, MT and Garzillo, EM}, title = {Peritoneal mesothelioma: description of a case and review of literature.}, journal = {International journal of immunopathology and pharmacology}, volume = {24}, number = {1 Suppl}, pages = {85S-88S}, pmid = {21329571}, issn = {0394-6320}, mesh = {Asbestos/toxicity ; Hernia, Inguinal/complications ; Humans ; Male ; Mesothelioma/diagnosis/*etiology/pathology ; Middle Aged ; Peritoneal Neoplasms/diagnosis/*etiology/pathology ; }, abstract = {It is universally recognized by the scientific community that asbestos, widely used in the past in many industrial sectors, is responsible for the onset of certain diseases of pleural and peritoneal serous membranes; in particular, Peritoneal Mesothelioma (PM) is an exceptional case, extremely rare malignancy of the abdominal cavity. In this work we describe a 62 years-old man, formerly exposed to asbestos, complains of dyspepsia associated with pain, abdominal swelling and mild difficulty during inspiration. After intraoperative biopsy of three masses found in abdomen, malignant peritoneal mesothelioma was diagnosed. The patient subsequently was subjected to cycles of chemotherapy and multiple palliative paracentesis, the patient died after about 12 months from diagnosis.}, } @article {pmid21329559, year = {2011}, author = {Nishimura, Y and Kumagai, N and Maeda, M and Hayashi, H and Fukuoka, K and Nakano, T and Miura, Y and Hiratsuka, J and Otsuki, T}, title = {Suppressive effect of asbestos on cytotoxicity of human NK cells.}, journal = {International journal of immunopathology and pharmacology}, volume = {24}, number = {1 Suppl}, pages = {5S-10S}, pmid = {21329559}, issn = {0394-6320}, mesh = {Animals ; Asbestos/*toxicity ; Cytotoxicity, Immunologic/*drug effects ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Humans ; Killer Cells, Natural/*drug effects/immunology ; Multiple Myeloma/immunology ; Natural Cytotoxicity Triggering Receptor 1/analysis ; Phosphorylation ; }, abstract = {Asbestos, a naturally occurring fibrous mineral, causes malignant mesothelioma (MM). However, it takes a very long time to develop MM, which suggests that effects other than tumorigenicity of asbestos might contribute to the development of MM, and one of the possible targets is anti-tumor immunity. Therefore, we examined the effect of asbestos exposure on human natural killer (NK) cells using the cell line of YT-A1, Peripheral blood mononuclear cells (PBMCs) cultures and specimens from patients with MM. In particular, we focused on expression of NK cell-activating receptors, including NKG2D, 2B4 and NKp46. Analysis of the YT-CB5 subline of YT-A1, cultured with CB for over 5 months, showed a decrease in cytotoxicity with low expressions of NKG2D and 2B4, although there were no decreases after about one month. YT-CB5 showed decreases in phosphorylation of extracellular signal-regulated kinase (ERK) and degranulation stimulated by antibodies to NKG2D. Peripheral blood (PB-) NK cells from MM patients also showed decreased cytotoxicity compared with healthy volunteers (HV), and was accompanied with low expression of NKp46 unlike YT-CB5. PBMCs cultured with CB resulted in decreased expression of NKp46 on NK cells, although this did not occur when using glass wool, an asbestos substitute. These results indicate that asbestos has the potential to suppress cytotoxicity of NK cells. In particular, it is noteworthy that both NK cells from MM patients and those from a culture of PBMCs derived from HVs with asbestos showed the same characteristic of decreased cytotoxicity with low expression of NKp46.}, } @article {pmid21549909, year = {2011}, author = {Massardier-Pilonchery, A and Bergeret, A}, title = {[Follow-up after occupational asbestos exposure: terms and devices in foreign].}, journal = {Revue des maladies respiratoires}, volume = {28}, number = {4}, pages = {556-564}, doi = {10.1016/j.rmr.2010.08.012}, pmid = {21549909}, issn = {1776-2588}, mesh = {Algorithms ; Asbestosis/*diagnosis/*epidemiology ; *Cross-Cultural Comparison ; Cross-Sectional Studies ; Europe ; Follow-Up Studies ; France ; Humans ; Lung Neoplasms/*diagnosis/*epidemiology ; Mass Chest X-Ray ; Mesothelioma/*diagnosis/*epidemiology ; Physical Examination ; Pleural Neoplasms/*diagnosis/*epidemiology ; Population Surveillance ; Retirement ; Spirometry ; Surveys and Questionnaires ; Tomography, X-Ray Computed ; }, abstract = {INTRODUCTION: Diseases, including cancer induced by asbestos, usually occur after many years of latency. The follow-up of employees must therefore continue after the end of their employment (retirement, redundancy, etc.) and such an arrangement has existed in France since 1996. This article reviews the literature on the post-employment monitoring arrangements that exist outside of France, particularly in other European countries, and their characteristics.

STATE OF ART: This research has revealed a limited number of national experiences in Germany, Spain, Finland, Italy, Norway, Poland, and Switzerland. The medical protocols generally involve: algorithm decisions, questionnaire, physical examination, chest radiography, CT scan, and/or spirometry.

PERSPECTIVES: Internationally, various methods exist to select employees for follow-up and to determine the frequency of subsequent examinations. Unlike Germany, which has a long experience of such medical follow-up, several of these programs are more recent.

CONCLUSIONS: Post-occupational medical surveillance of asbestos-related disease is uncommon, monitoring arrangements vary and depend on medical and also on social factors. The French system of post-occupational monitoring can undoubtedly improve but it bears comparison with arrangements in other countries, where these are even present.}, } @article {pmid21549904, year = {2011}, author = {Vincent, M and Chemarin, C}, title = {[Health impact of indoor mineral particle pollution].}, journal = {Revue des maladies respiratoires}, volume = {28}, number = {4}, pages = {496-502}, doi = {10.1016/j.rmr.2010.10.033}, pmid = {21549904}, issn = {1776-2588}, mesh = {Adult ; Air Pollution, Indoor/*adverse effects/analysis ; Asbestos/adverse effects/analysis ; Child ; Dust ; Female ; France ; Humans ; Male ; Mesothelioma/*etiology/prevention & control ; Mineral Fibers/*adverse effects/analysis ; Pleural Neoplasms/*etiology/prevention & control ; Pulmonary Disease, Chronic Obstructive/*etiology/prevention & control ; Respiratory Tract Infections/*etiology/prevention & control ; Risk Factors ; Silicates/adverse effects/analysis ; Silicon Dioxide/adverse effects/analysis ; Tobacco Smoke Pollution/adverse effects ; Ventilation ; }, abstract = {Mineral particle air pollution consists of both atmospheric pollution and indoor pollution. Indoor pollution comes from household products, cosmetics, combustion used to heat homes or cook food, smoking, hobbies or odd jobs. There is strong evidence that acute respiratory infections in children and chronic obstructive pulmonary disease in women are associated with indoor biomass smoke. Detailed questioning is essential to identify at risk activities and sampling of airborne particles may help with the identification of pollution risks. Particle elimination depends on the standard of ventilation of the indoor environment. Five per cent of French homes have levels of pollution greater than 180 μg/m[3] for PM 10 and 2% for PM 2.5. The principal mineral particle air pollutants are probably silica, talc, asbestos and carbon, whereas tobacco smoke leads to exposure to various ultrafine particles. The toxicity of these particles could be more related to surface exchange than to density. Tissue measurements by electron microscopy and microanalysis of particle samples may identify an uptake of particles similar to those in the environmental sample.}, } @article {pmid21549896, year = {2011}, author = {Paris, C}, title = {[Follow-up after occupational asbestos exposure. Public examination (texts of experts)].}, journal = {Revue des maladies respiratoires}, volume = {28}, number = {4}, pages = {407-408}, doi = {10.1016/j.rmr.2011.02.009}, pmid = {21549896}, issn = {1776-2588}, mesh = {Asbestosis/*diagnosis/*epidemiology ; *Cross-Cultural Comparison ; Humans ; Lung Neoplasms/*diagnosis/*epidemiology ; Mesothelioma/*diagnosis/*epidemiology ; Pleural Neoplasms/*diagnosis/*epidemiology ; }, } @article {pmid21543585, year = {2011}, author = {Tomasetti, M and Amati, M and Nocchi, L and Saccucci, F and Strafella, E and Staffolani, S and Tarquini, LM and Carbonari, D and Alleva, R and Borghi, B and Neuzil, J and Bracci, M and Santarelli, L}, title = {Asbestos exposure affects poly(ADP-ribose) polymerase-1 activity: role in asbestos-induced carcinogenesis.}, journal = {Mutagenesis}, volume = {26}, number = {5}, pages = {585-591}, doi = {10.1093/mutage/ger020}, pmid = {21543585}, issn = {1464-3804}, mesh = {Aged ; Asbestos/pharmacology/*toxicity ; Benzamides/pharmacology ; Carcinogens/pharmacology/*toxicity ; Cell Transformation, Neoplastic/*chemically induced ; Cells, Cultured ; DNA Damage/drug effects ; DNA Repair/genetics ; *Environmental Exposure ; Female ; Humans ; Lymphocytes/metabolism ; Male ; Mesothelioma/genetics/metabolism/pathology ; Middle Aged ; Poly(ADP-ribose) Polymerase Inhibitors ; Poly(ADP-ribose) Polymerases/genetics/*metabolism ; RNA, Messenger/genetics ; }, abstract = {Asbestos is known to induce malignant mesothelioma (MM) and other asbestos-related diseases. It is directly genotoxic by inducing DNA strand breaks and cytotoxic by promoting apoptosis in lung target cells. Poly(ADP-ribose) polymerase-1 (PARP1) is a nuclear zinc-finger protein with a function as a DNA damage sensor. To determine whether PARP1 is involved in asbestos-induced carcinogenesis, PARP1 expression and activity as well as DNA damage and repair were evaluated in circulating cells of asbestos-exposed subjects, MM patients and age-matched controls. PARP1 expression and activity were also evaluated in pleural biopsies of MM patients and compared with normal tissue. Accumulation of the pre-mutagenic 8-hydroxy-2'-deoxyguanosine and elevated PARP1 expression were found both in asbestos-exposed subjects and MM patients. Although PARP1 was highly expressed, its activity was relatively low. Low DNA repair efficiency was observed in lymphocytes from MM patients. High expression of PARP1 associated with low PARP activity was also found in MM biopsies. To mimic PARP1 dysfunction, PARP1 expression and activity were induced in immortalised mesothelial cells by their exposure to asbestos in the presence of a PARP1 inhibitor, which resulted in transformation of the cells. We propose that exposure to asbestos inhibits the PARP1 activity possibly resulting in higher DNA instability, thus causing malignant transformation.}, } @article {pmid21537890, year = {2011}, author = {Szeszenia-Dąbrowska, N and Swiątkowska, B and Szubert, Z and Wilczyńska, U}, title = {Asbestos in Poland: occupational health problems.}, journal = {International journal of occupational medicine and environmental health}, volume = {24}, number = {2}, pages = {142-152}, doi = {10.2478/s13382-011-0020-4}, pmid = {21537890}, issn = {1896-494X}, mesh = {Aged ; Asbestos/*adverse effects ; Female ; Humans ; Lung Diseases/*etiology ; Male ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; Occupational Exposure/adverse effects/legislation & jurisprudence/prevention & control/*standards ; Peritoneal Neoplasms/*etiology ; Pleural Neoplasms/*etiology ; Poland ; Workers' Compensation ; }, abstract = {The presentation addresses current problems of health risk and health effects associated with exposure to asbestos, including data on historical exposure and on currently valid occupational exposure limits. The quantity and types of the raw material used for the production of various asbestos products have also been discussed in relation to the particular types of asbestos-induced occupational diseases. The authors describe the medical care system for former asbestos workers and those currently exposed during removal of asbestos-containing products. The national system for medical certification of occupational asbestos-related diseases and the compensation procedure have been outlined as well. According to the parliamentary Act of 1997, importing, manufacture and sale of asbestos and asbestos-containing materials are prohibited in Poland. Thus, the assessment of asbestos exposure and the monitoring of health conditions of workers at asbestos-processing plants have become irrelevant. However, the delayed health effects attributable to past exposure continue to be the matter of concern for public health. Likewise, the environmental pollution from asbestos waste landfills in the vicinity of asbestos-processing plants (where high levels of asbestos fibre in ambient air have been recorded) will continue to be a serious public health problem. Presently, two programmes aimed at minimising the adverse effects of asbestos on population health are underway. One of them is the governmental programme for "Elimination of asbestos and asbestos-containing products used in Poland, 2002-2032". The programme was updated in 2009 to cover the workers contracted to perform demolition works and provide protective covers to asbestos waste landfills. This will be the exposed group who need prophylactic health care. The other is a programme of prophylactic examinations for former asbestos workers and is referred to as the AMIANTUS programme. Both programmes have been briefly described.}, } @article {pmid21534090, year = {2011}, author = {Below, JE and Cox, NJ and Fukagawa, NK and Hirvonen, A and Testa, JR}, title = {Factors that impact susceptibility to fiber-induced health effects.}, journal = {Journal of toxicology and environmental health. Part B, Critical reviews}, volume = {14}, number = {1-4}, pages = {246-266}, pmid = {21534090}, issn = {1521-6950}, mesh = {Age Factors ; Animals ; Asbestos/toxicity ; Carcinogens, Environmental/toxicity ; Chromosome Aberrations/chemically induced ; Cocarcinogenesis ; Disease Susceptibility/*chemically induced ; Environmental Pollutants/*toxicity ; Genetic Predisposition to Disease ; Humans ; Mesothelioma/chemically induced/epidemiology/genetics ; Mineral Fibers/*toxicity ; Nutritional Status ; Radiation Effects ; Risk ; Sex Characteristics ; Zeolites/toxicity ; }, abstract = {Asbestos and related fibers are associated with a number of adverse health effects, including malignant mesothelioma (MM), an aggressive cancer that generally develops in the surface serosal cells of the pleural, pericardial, and peritoneal cavities. Although approximately 80% of individuals with MM are exposed to asbestos, fewer than 5% of asbestos workers develop MM. In addition to asbestos, other mineralogical, environmental, genetic, and possibly viral factors might contribute to MM susceptibility. Given this complex etiology of MM, understanding susceptibility to MM needs to be a priority for investigators in order to reduce exposure of those most at risk to known environmental carcinogens. In this review, the current body of literature related to fiber-associated disease susceptibility including age, sex, nutrition, genetics, asbestos, and other mineral exposure is addressed with a focus on MM, and critical areas for further study are recommended.}, } @article {pmid21534088, year = {2011}, author = {Broaddus, VC and Everitt, JI and Black, B and Kane, AB}, title = {Non-neoplastic and neoplastic pleural endpoints following fiber exposure.}, journal = {Journal of toxicology and environmental health. Part B, Critical reviews}, volume = {14}, number = {1-4}, pages = {153-178}, pmid = {21534088}, issn = {1521-6950}, support = {P42 ES013660/ES/NIEHS NIH HHS/United States ; R01 ES016178/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Asbestos/administration & dosage/pharmacokinetics/*toxicity ; Biological Transport ; Carcinogens, Environmental/administration & dosage/pharmacokinetics/toxicity ; Environmental Pollutants/administration & dosage/pharmacokinetics/*toxicity ; Humans ; Mineral Fibers/*toxicity ; Pleural Diseases/*chemically induced/metabolism ; Pleural Neoplasms/*chemically induced/metabolism ; }, abstract = {Exposure to asbestos fibers is associated with non-neoplastic pleural diseases including plaques, fibrosis, and benign effusions, as well as with diffuse malignant pleural mesothelioma. Translocation and retention of fibers are fundamental processes in understanding the interactions between the dose and dimensions of fibers retained at this anatomic site and the subsequent pathological reactions. The initial interaction of fibers with target cells in the pleura has been studied in cellular models in vitro and in experimental studies in vivo. The proposed biological mechanisms responsible for non-neoplastic and neoplastic pleural diseases and the physical and chemical properties of asbestos fibers relevant to these mechanisms are critically reviewed. Understanding mechanisms of asbestos fiber toxicity may help us anticipate the problems from future exposures both to asbestos and to novel fibrous materials such as nanotubes. Gaps in our understanding have been outlined as guides for future research.}, } @article {pmid21534086, year = {2011}, author = {Mossman, BT and Lippmann, M and Hesterberg, TW and Kelsey, KT and Barchowsky, A and Bonner, JC}, title = {Pulmonary endpoints (lung carcinomas and asbestosis) following inhalation exposure to asbestos.}, journal = {Journal of toxicology and environmental health. Part B, Critical reviews}, volume = {14}, number = {1-4}, pages = {76-121}, pmid = {21534086}, issn = {1521-6950}, support = {R01 CA126939/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Asbestos/administration & dosage/chemistry/pharmacokinetics/*toxicity ; Asbestosis/*metabolism ; Biological Transport ; Body Burden ; Carcinogens, Environmental/administration & dosage/chemistry/pharmacokinetics/toxicity ; Carcinoma/*chemically induced/genetics/metabolism ; Chemical Phenomena ; Humans ; Inhalation Exposure/*adverse effects ; Lung/*drug effects/metabolism ; Lung Neoplasms/*chemically induced/genetics/metabolism ; Mineral Fibers/analysis/toxicity ; Mutagens/administration & dosage/chemistry/pharmacokinetics/toxicity ; Particulate Matter/administration & dosage/chemistry/pharmacokinetics/*toxicity ; Tissue Distribution ; }, abstract = {Lung carcinomas and pulmonary fibrosis (asbestosis) occur in asbestos workers. Understanding the pathogenesis of these diseases is complicated because of potential confounding factors, such as smoking, which is not a risk factor in mesothelioma. The modes of action (MOA) of various types of asbestos in the development of lung cancers, asbestosis, and mesotheliomas appear to be different. Moreover, asbestos fibers may act differentially at various stages of these diseases, and have different potencies as compared to other naturally occurring and synthetic fibers. This literature review describes patterns of deposition and retention of various types of asbestos and other fibers after inhalation, methods of translocation within the lung, and dissolution of various fiber types in lung compartments and cells in vitro. Comprehensive dose-response studies at fiber concentrations inhaled by humans as well as bivariate size distributions (lengths and widths), types, and sources of fibers are rarely defined in published studies and are needed. Species-specific responses may occur. Mechanistic studies have some of these limitations, but have suggested that changes in gene expression (either fiber-catalyzed directly or by cell elaboration of oxidants), epigenetic changes, and receptor-mediated or other intracellular signaling cascades may play roles in various stages of the development of lung cancers or asbestosis.}, } @article {pmid21534084, year = {2011}, author = {Case, BW and Abraham, JL and Meeker, G and Pooley, FD and Pinkerton, KE}, title = {Applying definitions of "asbestos" to environmental and "low-dose" exposure levels and health effects, particularly malignant mesothelioma.}, journal = {Journal of toxicology and environmental health. Part B, Critical reviews}, volume = {14}, number = {1-4}, pages = {3-39}, pmid = {21534084}, issn = {1521-6950}, mesh = {Animals ; Asbestos/administration & dosage/chemistry/*classification/*toxicity ; Body Burden ; Carcinogens, Environmental/administration & dosage/chemistry/*classification/*toxicity ; Environmental Exposure/adverse effects/legislation & jurisprudence ; Government Regulation ; Humans ; Inhalation Exposure/*adverse effects/legislation & jurisprudence ; Lung Neoplasms/chemically induced ; Mesothelioma/*chemically induced/mortality ; Occupational Exposure/adverse effects/legislation & jurisprudence ; Particulate Matter/administration & dosage/chemistry/classification/toxicity ; Risk ; Terminology as Topic ; }, abstract = {Although asbestos research has been ongoing for decades, this increased knowledge has not led to consensus in many areas of the field. Two such areas of controversy include the specific definitions of asbestos, and limitations in understanding exposure-response relationships for various asbestos types and exposure levels and disease. This document reviews the current regulatory and mineralogical definitions and how variability in these definitions has led to difficulties in the discussion and comparison of both experimental laboratory and human epidemiological studies for asbestos. This review also examines the issues of exposure measurement in both animal and human studies, and discusses the impact of these issues on determination of cause for asbestos-related diseases. Limitations include the lack of detailed characterization and limited quantification of the fibers in most studies. Associated data gaps and research needs are also enumerated in this review.}, } @article {pmid21532644, year = {2011}, author = {Prieto, MA and Suess, A and March, JC and Danet, A and Corral, OP and Martín, A}, title = {[Opinions and expectations of patients with health problems associated to asbestos exposure].}, journal = {Anales del sistema sanitario de Navarra}, volume = {34}, number = {1}, pages = {33-42}, pmid = {21532644}, issn = {2340-3527}, mesh = {Asbestos/*adverse effects ; Asbestosis/*etiology/therapy ; *Attitude to Health ; Humans ; Lung Neoplasms/*etiology/therapy ; Mesothelioma/*etiology/therapy ; Occupational Diseases/*etiology/therapy ; Occupational Exposure/*adverse effects ; Spain ; }, abstract = {BACKGROUND: The prevalence of diseases related to asbestos exposure requires the development of monitoring programs and specific health care protocols. The aim of this study is to determine the opinions and expectations of former workers of an asbestos factory, in order to adapt the care process to the needs of the affected population, and to learn about the activity of the association that represents them.

METHODS: Qualitative study. Focus groups with former employees of a corrugated asbestos factory, members of the association AVIDA (Seville). Recording and transcription of interviews. Discourse analysis with Nudist Vivo 1.0.

RESULTS: All respondents have health problems, including asbestosis, lung cancer and mesothelioma. Through the association, they are involved in an ongoing process of negotiation with the public administration, to improve healthcare, achieve recognition as having an occupational disease and the payment of compensation. The lack of monitoring and continuity in care is designated as the major problem in the current care process. They welcome the creation of special care units, the good treatment received and the quality of technical instruments in the public health system. On the contrary, they criticize the difficulties in finding an accurate diagnosis, the lack of continuity of care, and the bureaucratic difficulties and lack of specific care directed to affected relatives. The participants' expectations highlight their intention to participate in the development of future programs and protocols.

CONCLUSIONS: This study confirms the multifactor nature of diseases related to asbestos exposure and the importance of determining the needs and demands of the affected population in order to improve health care.}, } @article {pmid21532523, year = {2011}, author = {Kao, SC and Griggs, K and Lee, K and Armstrong, N and Clarke, S and Vardy, J and van Zandwijk, N and Burn, J and McCaughan, BC and Henderson, DW and Klebe, S}, title = {Validation of a minimal panel of antibodies for the diagnosis of malignant pleural mesothelioma.}, journal = {Pathology}, volume = {43}, number = {4}, pages = {313-317}, doi = {10.1097/PAT.0b013e32834642da}, pmid = {21532523}, issn = {1465-3931}, mesh = {Adenocarcinoma/metabolism/secondary ; Breast Neoplasms/metabolism/secondary ; Female ; Humans ; Immunohistochemistry/*methods ; Lung Neoplasms/metabolism/secondary ; Male ; Mesothelioma/*diagnosis/metabolism ; Pleura/*metabolism/pathology ; Pleural Neoplasms/*diagnosis/metabolism ; Sensitivity and Specificity ; }, abstract = {AIMS: We previously established the use of a minimal panel of antibodies as sufficient to diagnose most epithelial malignant mesothelioma (MPM). We aimed to validate this approach and investigate the utility of a D2-40 antibody.

METHODS: A series of 80 MPM patients selected for surgery and 21 consecutive patients with pleural metastatic carcinoma were included. A minimal panel of antibodies, consisting of calretinin, BG8 and CD15, and D2-40 was investigated.

RESULTS: There were 61 epithelial and 19 biphasic MPM as well as 12 metastatic lung, six breast (5 ductal adenocarcinomas, 1 mixed ductal/lobular adenocarcinoma), two serous papillary ovarian carcinomas and one moderately differentiated colorectal adenocarcinoma. The sensitivity of positive calretinin labelling to confirm the diagnosis of MPM was 97.5%, while the 'diagnostic sensitivities' of lack of labelling for BG8 and CD15 were 91.3% and 97.5%, respectively. The use of calretinin, BG8 and CD15 resulted in correct classification in 97.5% of all MPMs. All MPM cases investigated showed at least focal positive D2-40 labelling.

CONCLUSIONS: We have validated the usefulness of a minimal panel of antibodies with calretinin, BG8 and CD15 as the initial step to the diagnosis of MPM. D2-40 emerged as a helpful diagnostic tool for cases where our initial approach failed to conclusively diagnose MPM.}, } @article {pmid21526190, year = {2011}, author = {Altomare, DA and Menges, CW and Xu, J and Pei, J and Zhang, L and Tadevosyan, A and Neumann-Domer, E and Liu, Z and Carbone, M and Chudoba, I and Klein-Szanto, AJ and Testa, JR}, title = {Losses of both products of the Cdkn2a/Arf locus contribute to asbestos-induced mesothelioma development and cooperate to accelerate tumorigenesis.}, journal = {PloS one}, volume = {6}, number = {4}, pages = {e18828}, pmid = {21526190}, issn = {1932-6203}, support = {CA06927/CA/NCI NIH HHS/United States ; CA009035/CA/NCI NIH HHS/United States ; P01 CA114047/CA/NCI NIH HHS/United States ; P01CA114047/CA/NCI NIH HHS/United States ; P30 CA006927/CA/NCI NIH HHS/United States ; T32 CA009035/CA/NCI NIH HHS/United States ; }, mesh = {Alleles ; Animals ; Asbestos/*adverse effects ; Chromosomes, Mammalian/genetics ; Cyclin-Dependent Kinase Inhibitor p16/*deficiency/metabolism ; Gene Silencing ; Genetic Loci/*genetics ; Humans ; Mesothelioma/*genetics/*pathology ; Mice ; Precancerous Conditions/genetics/*pathology ; Tumor Suppressor Protein p14ARF/*deficiency/metabolism ; }, abstract = {The CDKN2A/ARF locus encompasses overlapping tumor suppressor genes p16(INK4A) and p14(ARF), which are frequently co-deleted in human malignant mesothelioma (MM). The importance of p16(INK4A) loss in human cancer is well established, but the relative significance of p14(ARF) loss has been debated. The tumor predisposition of mice singly deficient for either Ink4a or Arf, due to targeting of exons 1α or 1β, respectively, supports the idea that both play significant and nonredundant roles in suppressing spontaneous tumors. To further test this notion, we exposed Ink4a(+/-) and Arf(+/-) mice to asbestos, the major cause of MM. Asbestos-treated Ink4a(+/-) and Arf(+/-) mice showed increased incidence and shorter latency of MM relative to wild-type littermates. MMs from Ink4a(+/-) mice exhibited biallelic inactivation of Ink4a, loss of Arf or p53 expression and frequent loss of p15(Ink4b). In contrast, MMs from Arf(+/-) mice exhibited loss of Arf expression, but did not require loss of Ink4a or Ink4b. Mice doubly deficient for Ink4a and Arf, due to deletion of Cdkn2a/Arf exon 2, showed accelerated asbestos-induced MM formation relative to mice deficient for Ink4a or Arf alone, and MMs exhibited biallelic loss of both tumor suppressor genes. The tumor suppressor function of Arf in MM was p53-independent, since MMs with loss of Arf retained functional p53. Collectively, these in vivo data indicate that both CDKN2A/ARF gene products suppress asbestos carcinogenicity. Furthermore, while inactivation of Arf appears to be crucial for MM pathogenesis, the inactivation of both p16(Ink4a) and p19(Arf) cooperate to accelerate asbestos-induced tumorigenesis.}, } @article {pmid21513666, year = {2011}, author = {Ruiz-Tirado, ML and Olvera-Rodríguez, A and Díaz-Barranco, I and Ruiz-Romano, A and Castillo-Ruiz, N and Olvera-Quiroz, SE}, title = {[Malignant peritoneal mesothelioma. Case report and review of the literature].}, journal = {Revista medica del Instituto Mexicano del Seguro Social}, volume = {49}, number = {1}, pages = {79-84}, pmid = {21513666}, issn = {0443-5117}, mesh = {Aged, 80 and over ; Female ; Humans ; *Mesothelioma/diagnosis ; *Peritoneal Neoplasms/diagnosis ; }, abstract = {A woman 88 years old with a clinical picture initiated eight days before characterized by asthenia, adynamia, hyporexia, increase of the abdominal perimeter, pain and constipation. Her husband worked at the automotive industry for more than 30 years (brakes specialist). She had a history of hypertension; abdominal ultrasound showed a metastatic liver of unknown origin and ascites. An ascites sample was gotten. Malignant cells matching with malignant peritoneal mesothelioma were observed. The patient died 30 days after the diagnosis. The peritoneal mesothelioma is a rare form of cancer that can be benign or malignant. Incidence rate increases with age. It is more frequent in men and over 60 years with a survival from five to twelve months after diagnosis. The most important risk factor is the chronic labor exposition to asbestos that includes the family. The diagnosis is difficult even for experts. Additionally, we present a brief review of the literature.}, } @article {pmid21500129, year = {2011}, author = {Campbell, NP and Kindler, HL}, title = {Update on malignant pleural mesothelioma.}, journal = {Seminars in respiratory and critical care medicine}, volume = {32}, number = {1}, pages = {102-110}, doi = {10.1055/s-0031-1272874}, pmid = {21500129}, issn = {1098-9048}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Asbestos/*toxicity ; Biomarkers, Tumor/blood ; GPI-Linked Proteins/blood ; Humans ; Mass Screening/methods ; Mesothelin ; Mesothelioma/etiology/pathology/*therapy ; Osteopontin/blood ; Pleural Neoplasms/etiology/pathology/*therapy ; Prognosis ; Quality of Life ; }, abstract = {Malignant pleural mesothelioma is an aggressive cancer principally attributable to asbestos. Although the incidence is now declining in the United States, it will continue to increase worldwide until all nations institute regulations limiting asbestos use and exposure. This is a heterogeneous disease, with three pathological subtypes that yield very different outcomes. Stage is less important than histology in determining prognosis. The biomarkers serum mesothelin-related peptide and osteopontin are being evaluated for screening asbestos-exposed individuals and monitoring disease response. The optimal surgical procedure remains controversial because extrapleural pneumonectomy and pleurectomy/decortication can achieve similar results. The reference chemotherapy regimen, pemetrexed-cisplatin, improves survival and quality of life. Key questions about maintenance therapy and the optimal regimens for elderly and frail patients remain to be answered. Although few other cytotoxic drugs have activity, a surprising number of novel agents are being investigated.}, } @article {pmid21483773, year = {2011}, author = {Santarelli, L and Strafella, E and Staffolani, S and Amati, M and Emanuelli, M and Sartini, D and Pozzi, V and Carbonari, D and Bracci, M and Pignotti, E and Mazzanti, P and Sabbatini, A and Ranaldi, R and Gasparini, S and Neuzil, J and Tomasetti, M}, title = {Association of MiR-126 with soluble mesothelin-related peptides, a marker for malignant mesothelioma.}, journal = {PloS one}, volume = {6}, number = {4}, pages = {e18232}, pmid = {21483773}, issn = {1932-6203}, mesh = {Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Biomarkers, Tumor/blood/chemistry/genetics/*metabolism ; Case-Control Studies ; Down-Regulation/drug effects ; Early Detection of Cancer ; Environmental Exposure/adverse effects ; Epithelium/drug effects/metabolism ; Female ; GPI-Linked Proteins/*chemistry/*metabolism ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Male ; Mesothelin ; Mesothelioma/chemically induced/diagnosis/*metabolism/pathology ; MicroRNAs/blood/genetics/*metabolism ; Middle Aged ; Peptides/*chemistry/*metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Solubility ; }, abstract = {BACKGROUND: Improved detection methods for diagnosis of malignant pleural mesothelioma (MPM) are essential for early and reliable detection as well as treatment. Since recent data point to abnormal levels of microRNAs (miRNAs) in tumors, we hypothesized that a profile of deregulated miRNAs may be a marker of MPM and that the levels of specific miRNAs may be used for monitoring its progress.

METHODS AND RESULTS: miRNAs isolated from fresh-frozen biopsies of MPM patients were tested for the expression of 88 types of miRNA involved in cancerogenesis. Most of the tested miRNAs were downregulated in the malignant tissues compared with the normal tissues. Of eight significantly downregulated, three miRNAs were assayed in cancerous tissue and adjacent non-cancerous tissue sample pairs collected from 27 formalin-fixed, paraffin-embedded MPM tissues by quantitative RT-PCR. Among the miRNAs tested, only miR-126 significantly remained downregulated in the malignant tissues. Furthermore, the performance of the selected miR-126 as biomarker was evaluated in serum samples of asbestos-exposed subjects and MPM patients and compared with controls. MiR-126 was not affected by asbestos exposure, whereas it was found strongly associated with VEGF serum levels. Levels of miR-126 in serum, and its levels in patients' serum in association with a specific marker of MPM, SMRPs, correlate with subjects at high risk to develop MPM.

CONCLUSIONS AND SIGNIFICANCE: We propose miR-126, in association with SMRPs, as a marker for early detection of MPM. The identification of tumor biomarkers used alone or, in particular, in combination could greatly facilitate the surveillance procedure for cohorts of subjects exposed to asbestos.}, } @article {pmid21483691, year = {2011}, author = {Cortez, Bde A and Quassollo, G and Caceres, A and Machado-Santelli, GM}, title = {The fate of chrysotile-induced multipolar mitosis and aneuploid population in cultured lung cancer cells.}, journal = {PloS one}, volume = {6}, number = {4}, pages = {e18600}, pmid = {21483691}, issn = {1932-6203}, mesh = {*Aneuploidy ; Animals ; Asbestos, Serpentine/chemistry/*pharmacology ; Cell Line, Tumor ; Centrosome/drug effects/metabolism ; Chlorocebus aethiops ; Culture Media/chemistry/pharmacology ; Dose-Response Relationship, Drug ; Humans ; Lung Neoplasms/*pathology ; Mitosis/*drug effects ; Time Factors ; Vero Cells ; }, abstract = {Chrysotile is one of the six types of asbestos, and it is the only one that can still be commercialized in many countries. Exposure to other types of asbestos has been associated with serious diseases, such as lung carcinomas and pleural mesotheliomas. The association of chrysotile exposure with disease is controversial. However, in vitro studies show the mutagenic potential of chrysotile, which can induce DNA and cell damage. The present work aimed to analyze alterations in lung small cell carcinoma cultures after 48 h of chrysotile exposure, followed by 2, 4 and 8 days of recovery in fiber-free culture medium. Some alterations, such as aneuploid cell formation, increased number of cells in G2/M phase and cells in multipolar mitosis were observed even after 8 days of recovery. The presence of chrysotile fibers in the cell cultures was detected and cell morphology was observed by laser scanning confocal microscopy. After 4 and 8 days of recovery, only a few chrysotile fragments were present in some cells, and the cellular morphology was similar to that of control cells. Cells transfected with the GFP-tagged α-tubulin plasmid were treated with chrysotile for 24 or 48 h and cells in multipolar mitosis were observed by time-lapse microscopy. Fates of these cells were established: retention in metaphase, cell death, progression through M phase generating more than two daughter cells or cell fusion during telophase or cytokinesis. Some of them were related to the formation of aneuploid cells and cells with abnormal number of centrosomes.}, } @article {pmid21479901, year = {2011}, author = {Klebe, S and Henderson, DW}, title = {Early stages of mesothelioma, screening and biomarkers.}, journal = {Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer}, volume = {189}, number = {}, pages = {169-193}, doi = {10.1007/978-3-642-10862-4_10}, pmid = {21479901}, issn = {0080-0015}, mesh = {ATP Binding Cassette Transporter, Subfamily B ; Aquaporins/analysis ; Asbestos/toxicity ; Biomarkers, Tumor/*analysis ; CA-125 Antigen/blood ; CD56 Antigen/analysis ; Early Diagnosis ; GPI-Linked Proteins/analysis ; Gene Expression Profiling ; Glucose Transporter Type 1/analysis ; Glycoproteins/analysis ; Humans ; Membrane Glycoproteins/analysis ; Membrane Proteins/blood ; Mesothelioma/blood/*diagnosis/pathology ; Mucin-1/analysis ; Neoplasm Staging ; Osteopontin/blood ; Pleural Neoplasms/blood/*diagnosis/pathology ; Prognosis ; Tumor Suppressor Protein p53/analysis ; X-Linked Inhibitor of Apoptosis Protein/therapeutic use ; }, abstract = {The early diagnosis of mesothelioma is notoriously difficult, both from a clinical and pathological perspective. Patients often undergo several medical investigations without definitive diagnosis. The discovery of biomarkers that can be assessed in pleural effusions, histological samples, and serum may assist with the difficult early diagnosis of mesothelioma. In this chapter we focus on those markers that have been examined in the setting of either early diagnosis of mesothelioma in symptomatic individuals or that have been proposed as suitable for screening of asbestos-exposed individuals, with an emphasis on cytology and histology.}, } @article {pmid21479899, year = {2011}, author = {Dhalluin, X and Scherpereel, A}, title = {Chemotherapy and radiotherapy for mesothelioma.}, journal = {Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer}, volume = {189}, number = {}, pages = {127-147}, doi = {10.1007/978-3-642-10862-4_8}, pmid = {21479899}, issn = {0080-0015}, mesh = {Antineoplastic Agents/therapeutic use ; Asbestos/toxicity ; Combined Modality Therapy ; Gefitinib ; Genetic Therapy ; Histone Deacetylase Inhibitors/therapeutic use ; Humans ; Immunologic Factors/therapeutic use ; Mesothelioma/chemically induced/radiotherapy/*therapy ; Pleural Neoplasms/chemically induced/radiotherapy/*therapy ; Quinazolines/therapeutic use ; Ribonucleases/therapeutic use ; Thalidomide/therapeutic use ; }, abstract = {Previously considered to be rare, malignant pleural mesothelioma (MPM) is a highly aggressive tumor with an increasing incidence linked to asbestos exposure, its main etiological factor. MPM is also a very important issue because patients have usually a short survival (median <12 months) despite current treatments. Moreover an optimal treatment for MPM is not defined yet, even if ERS/ESTS experts recently provided clear and up-to-date guidelines on MPM management. These guidelines on chemotherapy and radiotherapy for mesothelioma, as well as new therapeutic developments, are presented in this chapter.}, } @article {pmid21479897, year = {2011}, author = {Neumann, V and Löseke, S and Tannapfel, A}, title = {Mesothelioma and analysis of tissue fiber content.}, journal = {Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer}, volume = {189}, number = {}, pages = {79-95}, doi = {10.1007/978-3-642-10862-4_6}, pmid = {21479897}, issn = {0080-0015}, mesh = {Aged ; Asbestos/*analysis/toxicity ; Asbestos, Amosite/analysis ; Asbestos, Amphibole/analysis/toxicity ; Asbestos, Crocidolite/analysis ; Asbestos, Serpentine/analysis/toxicity ; Female ; Germany ; Humans ; Lung Neoplasms/chemically induced/diagnosis ; Male ; Mesothelioma/chemically induced/*pathology ; Microscopy, Electron ; Middle Aged ; Mineral Fibers/*analysis/toxicity ; Occupational Diseases ; *Occupational Exposure ; Pleural Neoplasms/*chemically induced/*pathology ; }, abstract = {The strong relationship between mesothelioma and asbestos exposure is well established. The analysis of lung asbestos burden by light and electron microscopy assisted to understand the increased incidence of mesothelioma in asbestos mining and consuming nations.The data on the occupational exposure to asbestos are important information for the purpose of compensation of occupational disease No. 4105 (asbestos-associated mesothelioma) in Germany.However, in many cases the patients have forgotten conditions of asbestos exposure or had no knowledge about the used materials with components of asbestos. Mineral fiber analysis can provide valuable information for the research of asbestos-associated diseases and for the assessment of exposure. Because of the variability of asbestos exposure and long latency periods, the analysis of asbestos lung content is a relevant method for identification of asbestos-associated diseases. Also, sources of secondary exposure, so called "bystander exposition" or environmental exposure can be examined by mineral fiber analysis.Household contacts to asbestos are known for ten patients (1987-2009) in the German mesothelioma register; these patients lived together with family members working in the asbestos manufacturing industry.Analysis of lung tissue for asbestos burden offers information on the past exposure. The predominant fiber-type identified by electron microscopy in patients with mesothelioma is amphibole asbestos (crocidolite or amosite). Latency times (mean 42.5 years) and mean age at the time of diagnose in patients with mesothelioma are increasing (65.5 years). The decrease of median asbestos burden of the lung in mesothelioma patients results in disease manifestation at a higher age.Lung dust analyses are a relevant method for the determination of causation in mesothelioma. Analysis of asbestos burden of the lung and of fiber type provides insights into the pathogenesis of malignant mesothelioma. The most important causal factor for the development of mesothelioma is still asbestos exposure.}, } @article {pmid21479896, year = {2011}, author = {Tischoff, I and Neid, M and Neumann, V and Tannapfel, A}, title = {Pathohistological diagnosis and differential diagnosis.}, journal = {Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer}, volume = {189}, number = {}, pages = {57-78}, doi = {10.1007/978-3-642-10862-4_5}, pmid = {21479896}, issn = {0080-0015}, mesh = {Asbestos/toxicity ; Biomarkers, Tumor/analysis ; Diagnosis, Differential ; Female ; Humans ; Male ; Mesothelioma/*diagnosis/etiology/secondary ; Peritoneal Neoplasms/diagnosis/pathology ; Pleural Neoplasms/*diagnosis/etiology/pathology ; Pleurisy/diagnosis/pathology ; Prognosis ; Sarcoma/diagnosis/pathology ; Simian virus 40 ; }, abstract = {Malignant mesothelioma is a rare aggressive tumour arising from mesothelial cells of the pleural and peritoneal cavity including pericardium and tunica vaginalis testis. Malignant mesothelioma occurs predominantly in men (>90%). Asbestos exposure is the best known and evaluated risk factor with a long latency period between exposure and onset of malignant mesothelioma ranging from 15 to 60 years. Exposure to erionite leads to higher incidences of mesothelioma and play an important role in environmental exposure (Turkey). Other possible risk factors are radiation, recurrent pleuritis/peritonitis and simian virus 40 (SV 40).Malignant pleural mesothelioma is most common, whereas malignant peritoneal mesothelioma accounts only for 6-10%. Infrequent sites of origin are the pericardium and tunica vaginalis in 1-2%.Malignant mesothelioma shows either diffuse growth pattern or occurs as a localised tumour mass. Diffuse type represents an aggressive tumour with poor prognosis and is incurable in most cases.According to the WHO classification, three histological subtypes are distinguished: epithelioid, sarcomatoid and biphasic malignant mesothelioma.Rare variants are desmoplastic type, a subtype of sarcomatoid mesothelioma, undifferentiated type and deciduoid type. Epithelioid type is the most frequent one, but biphasic malignant mesothelioma occurs in 30%. Pure sarcomatoid or biphasic type is seen less frequently in malignant peritoneal mesothelioma than in its pleural counterpart.Well-differentiated papillary mesothelioma is a generally non-invasive mesothelioma with low malignant potential that arises mostly in females in the peritoneal cavity. Histological type is an important prognostic marker. Longest survival is seen in patients with epithelioid malignant mesothelioma. Sarcomatoid subtype has the worst prognosis.Malignant mesothelioma shows macroscopical and microscopical similarities to benign lesions and other malignancies. Therefore, reactive mesothelial proliferations on the one hand and secondary tumours resembling mesothelial cells as well as benign or rare mesothelial tumours on the other hand have to be distinguished. Additional immunohistochemistry is essential in histopathological assessment using a marker panel of antibodies.}, } @article {pmid21479894, year = {2011}, author = {Gill, RR}, title = {Imaging of mesothelioma.}, journal = {Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer}, volume = {189}, number = {}, pages = {27-43}, doi = {10.1007/978-3-642-10862-4_3}, pmid = {21479894}, issn = {0080-0015}, mesh = {Asbestos/toxicity ; Humans ; Magnetic Resonance Imaging ; Mediastinal Neoplasms/diagnosis/pathology ; Mesothelioma/*diagnosis/pathology ; Neoplasm Staging ; Pleural Neoplasms/diagnosis/pathology ; Positron-Emission Tomography ; Tomography, X-Ray Computed ; }, abstract = {Malignant pleural mesothelioma (MPM) is an asbestos-related neoplasm that originates in pleural mesothelial cells and progresses locally along the pleura until it encases the lungs and mediastinum, ultimately causing death. Imaging plays a crucial role in diagnosis and optimal management. Computed tomography (CT) continues to be the primary and initial imaging modality. Magnetic resonance imaging (MRI) complements CT scan and is superior in determining chest wall and diaphragmatic invasion. FDG18-PET/CT provides anatamo-metabolic information and is superior to both CT and MRI in overall staging and monitoring response to therapy. This chapter will detail the imaging finding of MPM and role of imaging in guiding management.}, } @article {pmid21479893, year = {2011}, author = {Craighead, JE}, title = {Epidemiology of mesothelioma and historical background.}, journal = {Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer}, volume = {189}, number = {}, pages = {13-25}, doi = {10.1007/978-3-642-10862-4_2}, pmid = {21479893}, issn = {0080-0015}, mesh = {Asbestos, Amosite/history/*toxicity ; Asbestos, Amphibole/history/*toxicity ; Asbestos, Crocidolite/history/*toxicity ; Asbestos, Serpentine/history/toxicity ; Female ; History, 20th Century ; Humans ; Lung Neoplasms/epidemiology/etiology ; Male ; Mesothelioma/*epidemiology/history ; Mining ; Occupational Diseases/epidemiology/etiology ; }, abstract = {Mesothelioma is a "new" malignant disease strongly associated with exposure to amphibole asbestos exposure (amosite and crocidolite) environmentally and in the work place. Nonetheless, in recent years, we have learned that many cases of mesothelioma are idiopathic, while some are caused by therapeutic irradiation or chronic inflammation in body cavities. This paper reviews the key epidemiological features of the malignancy in the context of the biological and mineralogical factors that influence mesothelioma development. These tumors challenge the diagnostic pathologist's acumen, the epidemiologist's skill in devising meaningful and definitive studies, the industrial hygienist's knowledge of environmental hazards in diverse occupational settings, and the clinician's skill in managing an intrepid and uniformly fatal malignancy.}, } @article {pmid21479892, year = {2011}, author = {Sporn, TA}, title = {Mineralogy of asbestos.}, journal = {Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer}, volume = {189}, number = {}, pages = {1-11}, doi = {10.1007/978-3-642-10862-4_1}, pmid = {21479892}, issn = {0080-0015}, mesh = {Asbestos/*chemistry/classification/toxicity ; Asbestos, Amosite/chemistry/toxicity ; Asbestos, Crocidolite/chemistry/toxicity ; Asbestos, Serpentine/chemistry/toxicity ; Asbestosis/*etiology/pathology ; Humans ; Mesothelioma/etiology/pathology ; Mineral Fibers/*toxicity ; }, abstract = {The term asbestos collectively refers to a group of naturally occurring fibrous minerals which have been exploited in numerous commercial and industrial settings and applications dating to antiquity. Its myriad uses as a "miracle mineral" owe to its remarkable properties of extreme resistance to thermal and chemical breakdown, tensile strength, and fibrous habit which allows it to be spun and woven into textiles. Abundant in nature, it has been mined considerably, and in all continents save Antarctica. The nomenclature concerning asbestos and its related species is complex, owing to the interest held therein by scientific disciplines such as geology, mineralogy and medicine, as well as legal and regulatory authorities. As fibrous silicates, asbestos minerals are broadly classified into the serpentine (chrysotile) and amphibole (crocidolite, amosite, tremolite, anthophyllite, actinolite) groups, both of which may also contain allied but nonfibrous forms of similar or even identical chemical composition, nonpathogenic to humans. Recently, fibrous amphiboles, not historically classified or regulated as asbestos (winchite, richterite), have been implicated in the causation of serious disease due to their profusion as natural contaminants of vermiculite, a commercially useful and nonfibrous silicate mineral. Although generally grouped, classified, and regulated collectively as asbestos, the serpentine and amphibole groups have different geologic occurrences and, more importantly, significant differences in crystalline structures and chemical compositions. These in turn impart differences in fiber structure and dimension, as well as biopersistence, leading to marked differences in relative potency for causing disease in humans for the group of minerals known as asbestos.}, } @article {pmid21473730, year = {2011}, author = {Cristaudo, A and Bonotti, A and Simonini, S and Bruno, R and Foddis, R}, title = {Soluble markers for diagnosis of malignant pleural mesothelioma.}, journal = {Biomarkers in medicine}, volume = {5}, number = {2}, pages = {261-273}, doi = {10.2217/bmm.11.18}, pmid = {21473730}, issn = {1752-0371}, mesh = {Biomarkers, Tumor/*blood ; Humans ; Mesothelioma/*blood/*diagnosis ; Pleural Neoplasms/*blood/*diagnosis ; Solubility ; }, abstract = {Malignant pleural mesothelioma (MPM) is a highly aggressive and invasive tumor, whose incidence is expected to peak, in many countries, at the end of the present decade, 20-40 years after the peak of asbestos use (asbestos being the most important etiological factor). MPM has a poor prognosis, in part, owing to a difficult and often late diagnosis hindered by a lack of available tests able to diagnose or predict this cancer in its early stages. Recently, there has been increased interest in noninvasive, economic and well-accepted diagnostic tests for screening of asbestos-exposed subjects, as well as for monitoring response of MPM patients to treatment. Several markers have been studied in biofluids, such as serum, plasma and pleural effusions, especially using ELISA, and some of them are still under investigation. However, only mesothelin and ostepontin have proven levels of sensitivity and specificity that are worth testing in the clinical setting.}, } @article {pmid21472445, year = {2011}, author = {Park, EJ and Roh, J and Kim, SN and Kang, MS and Han, YA and Kim, Y and Hong, JT and Choi, K}, title = {A single intratracheal instillation of single-walled carbon nanotubes induced early lung fibrosis and subchronic tissue damage in mice.}, journal = {Archives of toxicology}, volume = {85}, number = {9}, pages = {1121-1131}, doi = {10.1007/s00204-011-0655-8}, pmid = {21472445}, issn = {1432-0738}, mesh = {Animals ; Bronchoalveolar Lavage Fluid/chemistry/cytology/immunology ; Collagen/metabolism ; Cytokines/blood/immunology ; Data Interpretation, Statistical ; Dose-Response Relationship, Drug ; Environmental Pollutants/chemistry/*toxicity ; Flow Cytometry ; Instillation, Drug ; Intubation, Intratracheal ; Lung/*drug effects/immunology/pathology ; Lymphocytes/drug effects/immunology/pathology ; Male ; Mesothelin ; Mice ; Mice, Inbred ICR ; Microscopy, Electron, Transmission ; Nanotubes, Carbon/chemistry/*toxicity ; Particle Size ; Pulmonary Fibrosis/*chemically induced/immunology/pathology ; Surface Properties ; }, abstract = {Large amounts of nanomaterials may reach both the natural and occupational environments. This represents a potential health hazard. People have forecasted that CNTs may lead to the toxicity such as mesothelioma and fibrosis like asbestos. To identify dominant immune responses induced by SWCNTs, we investigated the composition of bronchioalveolar lavage (BAL) cells, the secretion of cytokine and collagen, histopathology, protein expression, and cell phenotypes over time after a single administration of single-walled carbon nanotubes (SWCNT). In our results, the number of total cells and macrophages remained at the up-regulated level until Day 28, neutrophils rapidly increased at Day 1, and lymphocytes increased from Day 7. In the BAL fluid, pro-inflammatory cytokines rapidly increased at Day 1 and remained at an up-regulated level throughout the experimental period. IL-12 and IL-10 rapidly increased at Day 1 after administration and remained at a similar level until Day 28. IFN-γ and IL-4 reached the maximum at Day 1, and IL-5, TGF-β, and collagen reached the maximum at Day 7. IL-13 and IL-17 increased in a time-dependent manner. The distribution of B cells and cytotoxic T cells markedly increased at Days 7 and 14, and fibrotic lesions were histopathologically observed at Days 7 and 14. The expressions of caspase-3, p53, COL1A1, COX-2, iNOS, MMP-9, and MMP-2 were also markedly increased at Days 7 and 14. In addition, the expression of mesothelin, iNOS, MMP-9, and p53 was up-regulated until Day 28. Based on these findings, we suggest that a single intratracheal instillation of SWCNTs may induce early lung fibrosis and subchronic tissue damage.}, } @article {pmid21465419, year = {2011}, author = {Kaufman, AJ and Flores, RM}, title = {Surgical treatment of malignant pleural mesothelioma.}, journal = {Current treatment options in oncology}, volume = {12}, number = {2}, pages = {201-216}, pmid = {21465419}, issn = {1534-6277}, mesh = {Humans ; Mesothelioma/mortality/*surgery ; Pleural Neoplasms/mortality/*surgery ; Treatment Outcome ; }, abstract = {Malignant Pleural Mesothelioma (MPM) remains a rare and lethal disease that is directly related to asbestos exposure in the vast majority of cases. While the total number of cases remains low compared to other malignancies, the worldwide incidence is expected to increase over the next twenty years. Currently, survival rates remain dismal and there is no standard therapy or consensus regarding treatment. However, over the last fifteen years there have been substantial improvements in the diagnosis and treatment of MPM, including easier and more accurate diagnostic techniques, improved methods of staging, more effective systemic therapy, a remarkable decrease in operative mortality, marked improvements in local control with adjuvant therapy, and perhaps most important, an emphasis on multidisciplinary care and multimodality clinical trials. Despite these advances, optimal therapy for these patients remains highly controversial and the role of surgery is actively debated. Most controversy centers on whether surgery increases survival and whether a survival benefit is best achieved with extrapleural pneumonectomy or pleurectomy/decortication within a multimodal regimen. To date, trimodality therapy that includes surgery, chemotherapy, and radiation offers the best survival advantage. It is generally accepted that the main goals of surgery, within the framework of a multimodality approach, is not only complete resection if possible, but more realistically, the resection of all macroscopic disease as an adjunct to the delivery of chemotherapy and radiation. The surgical options available to obtain this goal include extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D). There are no randomized trials directly comparing EPP and P/D and the level of evidence supporting either technique remains low. Ultimately, the choice of operation depends on multiple factors including: disease stage, the patient's cardiopulmonary reserve, surgeon experience and philosophy, and the extent of planned adjuvant therapy. Yet, despite the inherent biases in most studies, the data thus far illustrates significant survival advantages with both P/D and EPP and surgeons should consider these approaches in select patients.}, } @article {pmid21464917, year = {2011}, author = {Nayak, TK and Garmestani, K and Milenic, DE and Baidoo, KE and Brechbiel, MW}, title = {HER1-targeted 86Y-panitumumab possesses superior targeting characteristics than 86Y-cetuximab for PET imaging of human malignant mesothelioma tumors xenografts.}, journal = {PloS one}, volume = {6}, number = {3}, pages = {e18198}, pmid = {21464917}, issn = {1932-6203}, support = {//Intramural NIH HHS/United States ; }, mesh = {Animals ; Antibodies, Monoclonal/pharmacokinetics/*therapeutic use ; Antibodies, Monoclonal, Humanized ; Antibody Specificity/immunology ; Cetuximab ; ErbB Receptors/*metabolism ; Flow Cytometry ; Humans ; Isothiocyanates/chemistry ; Mesothelioma/*diagnostic imaging/*drug therapy ; Mice ; *Molecular Targeted Therapy ; Panitumumab ; Pentetic Acid/analogs & derivatives/chemistry ; *Positron-Emission Tomography ; Time Factors ; Tissue Distribution ; Xenograft Model Antitumor Assays ; Yttrium Radioisotopes ; }, abstract = {UNLABELLED: Malignant mesothelioma (MM), a rare form of cancer is often associated with previous exposure to fibrous minerals, such as asbestos. Asbestos exposure increases HER1-activity and expression in pre-clinical models. Additionally, HER1 over-expression is observed in the majority of MM cases. In this study, the utility of HER1-targeted chimeric IgG(1), cetuximab, and a human IgG(2), panitumumab, radiolabeled with (86)Y, were evaluated for PET imaging to detect MM non-invasively in vivo, and to select an antibody candidate for radioimmunotherapy (RIT).

METHODS: Radioimmunoconjugates (RICs) of cetuximab and panitumumab were prepared by conjugation with CHX-A''-DTPA followed by radiolabeling with (86)Y. The HER1 expression of NCI-H226, NCI-H2052, NCI-H2452 and MSTO-211H human mesothelioma cells was characterized by flow cytometry. In vivo biodistribution, pharmacokinetic analysis, and PET imaging were performed in tumor bearing athymic mice.

RESULTS: In vivo studies demonstrated high HER1 tumor uptake of both RICs. Significant reduction in tumor uptake was observed in mice co-injected with excess mAb (0.1 mg), demonstrating that uptake in the tumor was receptor specific. Significant differences were observed in the in vivo characteristics of the RICs. The blood clearance T(½)α of (86)Y-cetuximab (0.9-1.1 h) was faster than (86)Y-panitumumab (2.6-3.1 h). Also, the tumor area under the curve (AUC) to liver AUC ratios of (86)Y-panitumumab were 1.5 to 2.5 times greater than (86)Y-cetuximab as observed by the differences in PET tumor to background ratios, which could be critical when imaging orthotopic tumors and concerns regarding radiation doses to normal organs such as the liver.

CONCLUSION: This study demonstrates the more favorable HER1-targeting characteristics of (86)Y-panitumumab than (86)Y-cetuximab for non-invasive assessment of the HER1 status of MM by PET imaging. Due to lower liver uptake, panitumumab based immunoconjugates may fare better in therapy than corresponding cetuximab based immunoconjugates.}, } @article {pmid21463977, year = {2011}, author = {Park, EK and Takahashi, K and Hoshuyama, T and Cheng, TJ and Delgermaa, V and Le, GV and Sorahan, T}, title = {Global magnitude of reported and unreported mesothelioma.}, journal = {Environmental health perspectives}, volume = {119}, number = {4}, pages = {514-518}, pmid = {21463977}, issn = {1552-9924}, mesh = {Air Pollution, Indoor/analysis/*statistics & numerical data ; Asbestos/*analysis ; Carcinogens/*analysis ; Environmental Exposure/statistics & numerical data ; Humans ; Mesothelioma/*epidemiology ; }, abstract = {BACKGROUND: Little is known about the global magnitude of mesothelioma. In particular, many developing countries, including some with extensive historical use of asbestos, do not report mesothelioma.

OBJECTIVES: We estimated the global magnitude of mesothelioma accounting for reported and unreported cases.

METHODS: For all countries with available data on mesothelioma frequency and asbestos use (n=56), we calculated the 15-year cumulative number of mesotheliomas during 1994-2008 from data available for fewer years and assessed its relationship with levels of cumulative asbestos use during 1920-1970. We used this relationship to predict the number of unreported mesotheliomas in countries for which no information on mesothelioma is available but which have recorded asbestos use (n=33).

RESULTS: Within the group of 56 countries with data on mesothelioma occurrence and asbestos use, the 15-year cumulative number of mesothelioma was approximately 174,300. There was a statistically significant positive linear relation between the log-transformed national cumulative mesothelioma numbers and the log-transformed cumulative asbestos use (adjusted R(2)=0.83, p<0.0001). Extrapolated to the group of 33 countries without reported mesothelioma, a total of approximately 38,900 (95% confidence interval, 36,700-41,100) mesothelioma cases were estimated to have occurred in the 15-year period (1994-2008).

CONCLUSIONS: We estimate conservatively that, globally, one mesothelioma case has been overlooked for every four to five reported cases. Because our estimation is based on asbestos use until 1970, the many countries that increased asbestos use since then should anticipate a higher disease burden in the immediate decades ahead.}, } @article {pmid21461290, year = {2011}, author = {Park, YJ and Kong, HJ and Jang, HC and Shin, HS and Oh, HK and Park, JS}, title = {Malignant mesothelioma of the spermatic cord.}, journal = {Korean journal of urology}, volume = {52}, number = {3}, pages = {225-229}, pmid = {21461290}, issn = {2005-6745}, abstract = {Primary tumors arising from the spermatic cord are very rare. Mesothelioma derives from the mesothelial cells lining the serous membrane, such as the pleura, peritoneum, and tunica vaginalis of testis. Paratesticular malignant mesothelioma (MM), which usually presents as a hydrocele or intrascrotal mass, accounts for 0.3% to 1.4% of MMs. MMs of the spermatic cord account for less than 10% of paratesticular MMs. We report a case of MM of the spermatic cord in a 65-year-old man who primarily presented to the hospital with a left inguinal mass. Following the diagnosis after surgery, he was found to have a contralateral right inguinal mass and died in 6 months. Despite their rare occurrence in the spermatic cord, MMs need to be suspected, especially in patients with a history of asbestos exposure.}, } @article {pmid21459708, year = {2011}, author = {Haynes, RC}, title = {Where there is asbestos, there is mesothelioma: filling in the data blanks.}, journal = {Environmental health perspectives}, volume = {119}, number = {4}, pages = {A177}, doi = {10.1289/ehp.119-a177b}, pmid = {21459708}, issn = {1552-9924}, mesh = {Air Pollution, Indoor/analysis/*statistics & numerical data ; Asbestos/*analysis ; Carcinogens/*analysis ; Humans ; Mesothelioma/*epidemiology ; }, } @article {pmid21454801, year = {2011}, author = {Shukla, A and Barrett, TF and MacPherson, MB and Hillegass, JM and Fukagawa, NK and Swain, WA and O'Byrne, KJ and Testa, JR and Pass, HI and Faux, SP and Mossman, BT}, title = {An extracellular signal-regulated kinase 2 survival pathway mediates resistance of human mesothelioma cells to asbestos-induced injury.}, journal = {American journal of respiratory cell and molecular biology}, volume = {45}, number = {5}, pages = {906-914}, pmid = {21454801}, issn = {1535-4989}, support = {P01 CA114047/CA/NCI NIH HHS/United States ; R01 CA106567/CA/NCI NIH HHS/United States ; P20 RR016462/RR/NCRR NIH HHS/United States ; P30 CA006927/CA/NCI NIH HHS/United States ; CA-06927/CA/NCI NIH HHS/United States ; }, mesh = {Asbestos, Crocidolite/*toxicity ; Cell Line ; Cell Survival/drug effects ; Enzyme Inhibitors/pharmacology ; ErbB Receptors/metabolism ; Gene Expression/drug effects ; Humans ; MAP Kinase Kinase 1/antagonists & inhibitors ; MAP Kinase Kinase 2/antagonists & inhibitors ; Mesothelioma/*chemically induced/*enzymology ; Mitogen-Activated Protein Kinase 1/*metabolism ; Pleural Neoplasms/*chemically induced/*enzymology ; RNA, Small Interfering/metabolism ; Signal Transduction/drug effects ; }, abstract = {We hypothesized that normal human mesothelial cells acquire resistance to asbestos-induced toxicity via induction of one or more epidermal growth factor receptor (EGFR)-linked survival pathways (phosphoinositol-3-kinase/AKT/mammalian target of rapamycin and extracellular signal-regulated kinase [ERK] 1/2) during simian virus 40 (SV40) transformation and carcinogenesis. Both isolated HKNM-2 mesothelial cells and a telomerase-immortalized mesothelial line (LP9/TERT-1) were more sensitive to crocidolite asbestos toxicity than an SV40 Tag-immortalized mesothelial line (MET5A) and malignant mesothelioma cell lines (HMESO and PPM Mill). Whereas increases in phosphorylation of AKT (pAKT) were observed in MET5A cells in response to asbestos, LP9/TERT-1 cells exhibited dose-related decreases in pAKT levels. Pretreatment with an EGFR phosphorylation or mitogen-activated protein kinase kinase 1/2 inhibitor abrogated asbestos-induced phosphorylated ERK (pERK) 1/2 levels in both LP9/TERT-1 and MET5A cells as well as increases in pAKT levels in MET5A cells. Transient transfection of small interfering RNAs targeting ERK1, ERK2, or AKT revealed that ERK1/2 pathways were involved in cell death by asbestos in both cell lines. Asbestos-resistant HMESO or PPM Mill cells with high endogenous levels of ERKs or AKT did not show dose-responsive increases in pERK1/ERK1, pERK2/ERK2, or pAKT/AKT levels by asbestos. However, small hairpin ERK2 stable cell lines created from both malignant mesothelioma lines were more sensitive to asbestos toxicity than shERK1 and shControl lines, and exhibited unique, tumor-specific changes in endogenous cell death-related gene expression. Our results suggest that EGFR phosphorylation is causally linked to pERK and pAKT activation by asbestos in normal and SV40 Tag-immortalized human mesothelial cells. They also indicate that ERK2 plays a role in modulating asbestos toxicity by regulating genes critical to cell injury and survival that are differentially expressed in human mesotheliomas.}, } @article {pmid21452191, year = {2011}, author = {Strauchen, JA}, title = {Rarity of malignant mesothelioma prior to the widespread commercial introduction of asbestos: the Mount Sinai autopsy experience 1883-1910.}, journal = {American journal of industrial medicine}, volume = {54}, number = {6}, pages = {467-469}, doi = {10.1002/ajim.20951}, pmid = {21452191}, issn = {1097-0274}, mesh = {Asbestos/*toxicity ; Autopsy/statistics & numerical data ; Cause of Death/trends ; History, 19th Century ; History, 20th Century ; Humans ; Mesothelioma/epidemiology/history/*mortality ; New York City/epidemiology ; Occupational Exposure/*adverse effects/history ; Pleura ; Retrospective Studies ; Risk Assessment ; }, abstract = {BACKGROUND: Most malignant mesotheliomas are related to asbestos exposure. Whether malignant mesothelioma occurs in the absence of asbestos exposure remains unsettled. To address this question we reviewed a series of 2,025 autopsies performed at the Mount Sinai Hospital between 1883 and 1910, prior to the widespread commercial introduction of asbestos.

METHODS: Retrospective autopsy review.

RESULTS: No cases of malignant mesothelioma were identified in 2,025 autopsies performed between 1883 and 1910.

CONCLUSIONS: Malignant mesothelioma was rare prior to the widespread commercial introduction of asbestos.}, } @article {pmid21449920, year = {2011}, author = {LE, GV and Takahashi, K and Park, EK and Delgermaa, V and Oak, C and Qureshi, AM and Aljunid, SM}, title = {Asbestos use and asbestos-related diseases in Asia: past, present and future.}, journal = {Respirology (Carlton, Vic.)}, volume = {16}, number = {5}, pages = {767-775}, doi = {10.1111/j.1440-1843.2011.01975.x}, pmid = {21449920}, issn = {1440-1843}, mesh = {Asbestos/*adverse effects ; Asia/epidemiology ; Environmental Health/*trends ; Epidemics ; Humans ; Lung Diseases/*chemically induced/*epidemiology/mortality ; Lung Neoplasms/chemically induced/epidemiology/mortality ; Mesothelioma/chemically induced/epidemiology/mortality ; Retrospective Studies ; Survival Rate ; World Health Organization ; }, abstract = {BACKGROUND AND OBJECTIVE: Although there are growing concerns about the global epidemic of asbestos-related diseases (ARD), the current status of asbestos use and ARD in Asia is elusive. We conducted a descriptive analysis of available data on asbestos use and ARD to characterize the current situation in Asia.

METHODS: We used descriptive indicators of per capita asbestos use (kilograms per capita per year) and age-adjusted mortality rates (AAMR, persons per million population per year) by country and for the region, with reference to the world.

RESULTS: The proportion of global asbestos use attributed to Asia has been steadily increasing over the years from 14% (1920-1970) to 33% (1971-2000) to 64% (2001-2007). This increase has been reflected in the absolute level of per capita use across a wide range of countries. In contrast, 12 882 ARD deaths have been recorded cumulatively in Asia, which is equivalent to only 13% of the cumulative number of ARD deaths in the world during the same period. The highest AAMR were recorded in Cyprus (4.8), Israel (3.7) and Japan (3.3), all of which have banned asbestos use.

CONCLUSIONS: There is a paucity of information concerning the current situation of ARD in Asia. The marked increase in asbestos use in Asia since 1970, however, is likely to trigger a surge of ARD in the immediate decades ahead.}, } @article {pmid21437912, year = {2011}, author = {Rena, O and Boldorini, LR and Gaudino, E and Casadio, C}, title = {Epidermal growth factor receptor overexpression in malignant pleural mesothelioma: prognostic correlations.}, journal = {Journal of surgical oncology}, volume = {104}, number = {6}, pages = {701-705}, doi = {10.1002/jso.21901}, pmid = {21437912}, issn = {1096-9098}, mesh = {Aged ; ErbB Receptors/*genetics/metabolism ; Female ; Follow-Up Studies ; Gene Amplification ; Gene Dosage ; Humans ; Immunoenzyme Techniques ; In Situ Hybridization, Fluorescence ; Male ; Mesothelioma/*genetics/metabolism/pathology ; Mutation/genetics ; Pleural Effusion, Malignant/*genetics/metabolism/pathology ; Pleural Neoplasms/*genetics/metabolism/pathology ; Prognosis ; Survival Rate ; }, abstract = {BACKGROUND: To evaluate epidermal growth factor receptor (EGFR) phenotypic expression and related gene status in malignant pleural mesothelioma (MPM) and to correlate the results with patients' prognosis.

METHOD: Eighty-three cases of MPM specimens were submitted to immunohistochemical (IHC) staining to evaluate the expression of EGFR protein; positive cases were submitted to fluorescence in situ hybridization (FISH) to investigate the gene status. Results were correlated with clinico-pathological characteristics and long-term survival.

RESULTS: Thirty-eight cases (46%) demonstrated a positive IHC reaction [30/57 (52%) epithelial and 8/20 (40%) biphasic whereas sarcomatous MPM were negative]. No association was recorded between EGFR IHC positive staining and age, gender, or asbestos exposure. Three out of 38 (8%) cases submitted to FISH were positive revealing gene amplification or polysomy. Mean follow-up was 15.4  months (range 2-44). Epithelial subtype only was confirmed to affect prognosis (2-years survival rate 40 vs. 18% for non-epithelial subtype, P = 0.042). When epithelial MPM patients were considered, IHC EGFR positive staining was demonstrated to be a negative prognostic factor (2-years survival rate 26 vs. 60% for IHC EGFR negative staining; P = 0.026).

CONCLUSIONS: EGFR overexpression is identified by IHC in 52% of epithelial MPM and is demonstrated to be a factor negatively affecting prognosis. Phenotypic overexpression seems not to be related to gene status alteration.}, } @article {pmid21436629, year = {2011}, author = {Kao, SC and Reid, G and van Zandwijk, N and Henderson, DW and Klebe, S}, title = {Molecular biomarkers in malignant mesothelioma: state of the art.}, journal = {Pathology}, volume = {43}, number = {3}, pages = {201-212}, doi = {10.1097/PAT.0b013e3283445e67}, pmid = {21436629}, issn = {1465-3931}, mesh = {Biomarkers, Tumor/*analysis ; DNA, Neoplasm/analysis ; Early Diagnosis ; GPI-Linked Proteins/analysis ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Mass Screening/methods ; Mesothelin ; Mesothelioma/*diagnosis ; Pleural Neoplasms/*diagnosis ; }, abstract = {Malignant mesothelioma (MM) is an aggressive tumour affecting the mesothelial surfaces of the pleural and peritoneal cavities and, rarely, the pericardium and the tunica vaginalis testis. Despite a ban of asbestos in many industrialised nations, the present high incidence of MM is expected to continue, due to the long latency period between first asbestos exposure and occurrence of disease, making it an important health issue for the future. The diagnosis of MM can be difficult, both from a clinical and pathological perspective. It is not unusual for patients to undergo several medical investigations without definitive diagnosis early in their course of illness. Understandably, there is intense interest in the discovery of markers that can be assessed in pleural effusions, histological specimens, and serum to assist with the difficult early diagnosis of MM. Considering the primary aetiological role of asbestos, there is theoretically an easily identifiable target population for screening with a biomarker with adequate sensitivity and specificity or with a combination of biomarkers. In this review we focus on biomarkers that have been examined in the setting of either early diagnosis of MM in symptomatic patients or screening of asbestos-exposed individuals.}, } @article {pmid21436488, year = {2011}, author = {Merler, E}, title = {[Italian fund for the asbestos victims: a very unsatisfactory implementation].}, journal = {Epidemiologia e prevenzione}, volume = {35}, number = {1}, pages = {8}, pmid = {21436488}, issn = {1120-9763}, mesh = {Asbestosis/*economics/epidemiology ; Compensation and Redress/*legislation & jurisprudence ; Environmental Exposure ; Financial Management/legislation & jurisprudence/*organization & administration/statistics & numerical data ; Financing, Government/*organization & administration ; France ; Humans ; Italy/epidemiology ; Mesothelioma/*economics/epidemiology/etiology ; Occupational Exposure ; Pleural Neoplasms/*economics/epidemiology/etiology ; Social Justice ; Workers' Compensation/economics/*legislation & jurisprudence ; }, } @article {pmid21431813, year = {2011}, author = {Kudo, Y and Aizawa, Y}, title = {Cytotoxicity and solubility evaluation of two types of whiskers by cell magnetometry.}, journal = {Environmental health and preventive medicine}, volume = {16}, number = {5}, pages = {327-334}, pmid = {21431813}, issn = {1347-4715}, mesh = {Aluminum/*toxicity ; Animals ; Antimony/toxicity ; Borates/*toxicity ; Construction Materials/toxicity ; Enzyme Assays/methods ; L-Lactate Dehydrogenase/antagonists & inhibitors ; Macrophages, Alveolar/*pathology ; Magnetometry/*methods ; Rats ; Rats, Inbred F344 ; Solubility ; Tin Compounds/toxicity ; Toxicity Tests/*methods ; }, abstract = {OBJECTIVES: We investigated two types of whiskers, an antimony-containing tin-oxide-coated aluminum borate whisker (CABW) and an aluminum borate whisker (ABW), which are asbestos substitutes, in order to evaluate the safety of these fibers.

METHODS: The cytotoxicity and solubility of CABW and ABW were evaluated by cell magnetometry, LDH assay and solubility test.

RESULTS: ABW was found to be cytotoxic by cell magnetometry and slightly less soluble than CABW. In addition, it was found that the solubility of both fibers was intermediate between that of chrysotile and rock wool, as compared to our previous test results. Regarding the LDH assay, no significant difference was found among the fibers tested. These findings suggested that CABW, the surface of which is coated with antimony-containing tin oxide, had lower cytotoxicity and slightly higher solubility than ABW.

CONCLUSIONS: This study was only a short-term cytotoxicity and solubility study. Therefore, further safety assessment should be carried out in long-term experiments to examine the half-life of these fibers and monitor the potential development of lung carcinoma or mesothelioma after intratracheal instillation of these fibers in rats.}, } @article {pmid21422006, year = {2011}, author = {Kielkowski, D and Nelson, G and Bello, B and Kgalamono, S and Phillips, JI}, title = {Trends in mesothelioma mortality rates in South Africa: 1995-2007.}, journal = {Occupational and environmental medicine}, volume = {68}, number = {7}, pages = {547-549}, doi = {10.1136/oem.2010.062182}, pmid = {21422006}, issn = {1470-7926}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos ; Female ; Humans ; Male ; Mesothelioma/*mortality ; Middle Aged ; Mining/statistics & numerical data/trends ; Mortality/trends ; Sex Distribution ; South Africa/epidemiology ; Young Adult ; }, abstract = {OBJECTIVE: In 1984, South Africa had one of the highest mesothelioma rates in the world. The objective of this analysis was to calculate mesothelioma mortality rates in the South African population from 1995 to 2007.

METHODS: Annual mortality data and midyear population estimates were used to compute mortality rates by age group and gender for each year. The WHO World Standard Population was used as the reference population to calculate age-adjusted rates. Poisson regression models were used to test for trends.

RESULTS: In total, 2509 deaths due to mesothelioma were identified in the study period: 1920 in men and 588 in women. There were no significant trends in mesothelioma mortality rates: age-adjusted mortality rates fluctuated from 11 to 16 and from 3 to 5 per million per year for men and women, respectively.

CONCLUSION: These mortality rates are much lower than expected, given the historical production and use of, and high exposure to, asbestos in South Africa. Possible reasons for this are discussed, including the effect of HIV which has been instrumental in reducing the life expectancy of South Africans in the last two decades. Asbestos-exposed individuals may not live long enough to develop mesothelioma. Competing causes of death need to be taken into account when constructing models to predict mesothelioma mortality rates.}, } @article {pmid21412769, year = {2012}, author = {Carbone, M and Ly, BH and Dodson, RF and Pagano, I and Morris, PT and Dogan, UA and Gazdar, AF and Pass, HI and Yang, H}, title = {Malignant mesothelioma: facts, myths, and hypotheses.}, journal = {Journal of cellular physiology}, volume = {227}, number = {1}, pages = {44-58}, pmid = {21412769}, issn = {1097-4652}, support = {R01 CA106567-01A1/CA/NCI NIH HHS/United States ; P01 CA114047/CA/NCI NIH HHS/United States ; R01 CA106567/CA/NCI NIH HHS/United States ; P01 CA114047-01A1/CA/NCI NIH HHS/United States ; P50 CA070907/CA/NCI NIH HHS/United States ; P30 CA071789/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Mesothelioma/*epidemiology/*etiology ; }, abstract = {Malignant mesothelioma (MM) is a neoplasm arising from mesothelial cells lining the pleural, peritoneal, and pericardial cavities. Over 20 million people in the US are at risk of developing MM due to asbestos exposure. MM mortality rates are estimated to increase by 5-10% per year in most industrialized countries until about 2020. The incidence of MM in men has continued to rise during the past 50 years, while the incidence in women appears largely unchanged. It is estimated that about 50-80% of pleural MM in men and 20-30% in women developed in individuals whose history indicates asbestos exposure(s) above that expected from most background settings. While rare for women, about 30% of peritoneal mesothelioma in men has been associated with exposure to asbestos. Erionite is a potent carcinogenic mineral fiber capable of causing both pleural and peritoneal MM. Since erionite is considerably less widespread than asbestos, the number of MM cases associated with erionite exposure is smaller. Asbestos induces DNA alterations mostly by inducing mesothelial cells and reactive macrophages to secrete mutagenic oxygen and nitrogen species. In addition, asbestos carcinogenesis is linked to the chronic inflammatory process caused by the deposition of a sufficient number of asbestos fibers and the consequent release of pro-inflammatory molecules, especially HMGB-1, the master switch that starts the inflammatory process, and TNF-alpha by macrophages and mesothelial cells. Genetic predisposition, radiation exposure and viral infection are co-factors that can alone or together with asbestos and erionite cause MM. J. Cell. Physiol. 227: 44-58, 2012. © 2011 Wiley Periodicals, Inc.}, } @article {pmid21406385, year = {2011}, author = {Clin, B and Morlais, F and Launoy, G and Guizard, AV and Dubois, B and Bouvier, V and Desoubeaux, N and Marquignon, MF and Raffaelli, C and Paris, C and Galateau-Salle, F and Guittet, L and Letourneux, M}, title = {Cancer incidence within a cohort occupationally exposed to asbestos: a study of dose--response relationships.}, journal = {Occupational and environmental medicine}, volume = {68}, number = {11}, pages = {832-836}, doi = {10.1136/oem.2010.059790}, pmid = {21406385}, issn = {1470-7926}, mesh = {Adult ; Asbestos/*administration & dosage/toxicity ; Carcinogens/*administration & dosage/toxicity ; Colorectal Neoplasms/chemically induced/epidemiology ; Female ; France/epidemiology ; Humans ; Incidence ; Lung Neoplasms/chemically induced/epidemiology ; Male ; Mesothelioma/chemically induced/epidemiology ; Neoplasms/chemically induced/*epidemiology ; Occupational Diseases/chemically induced/*epidemiology ; Occupational Exposure/adverse effects/*statistics & numerical data ; Peritoneal Neoplasms/chemically induced/epidemiology ; Retrospective Studies ; Risk Assessment ; }, abstract = {OBJECTIVES: The aim of our study was to analyse the dose-response relationship between occupational asbestos exposure and risk of cancer.

METHODS: Our study was a retrospective morbidity study based on 2024 subjects occupationally exposed to asbestos, conducted over the period 1 January 1978 to 31 December 2004. Analysis of the dose-response relationship between occupational asbestos exposure, as a time-dependant variable, and risk of cancer was performed using a Cox model. In order to account for the effect of latency, we conducted the analysis with a lag of 10 years.

RESULTS: 285 cases of cancers were observed in our cohort. The relative risk of pleuro-peritoneal mesothelioma, lung cancer and colorectal cancer associated with asbestos exposure, adjusted for age as a time-dependant variable and for sex, was correlated with exposure intensity (or average exposure level, AEL). The risk of cancer, whatever the anatomical site, did not increase with the duration of exposure to asbestos.

CONCLUSION: While confirming the established relationship between asbestos exposure and pleuropulmonary and peritoneal cancers, this study also suggests a causal relationship between asbestos exposure and colorectal cancer.}, } @article {pmid21406258, year = {2011}, author = {Haniu, H and Matsuda, Y and Usui, Y and Aoki, K and Shimizu, M and Ogihara, N and Hara, K and Okamoto, M and Takanashi, S and Ishigaki, N and Nakamura, K and Kato, H and Saito, N}, title = {Toxicoproteomic evaluation of carbon nanomaterials in vitro.}, journal = {Journal of proteomics}, volume = {74}, number = {12}, pages = {2703-2712}, doi = {10.1016/j.jprot.2011.03.004}, pmid = {21406258}, issn = {1876-7737}, mesh = {Animals ; Asbestos/toxicity ; Carcinogens/toxicity ; Drug Evaluation, Preclinical/methods ; Humans ; Nanotubes, Carbon/*adverse effects ; Particle Size ; Proteomics/*methods ; Time Factors ; }, abstract = {Carbon nanotubes (CNTs) have already been successfully implemented in various fields, and they are anticipated to have innovative applications in medical science. However, CNTs have asbestos-like properties, such as their nanoscale size and high aspect ratio (>100). Moreover, CNTs may persist in the body for a long time. These properties are thought to cause malignant mesothelioma and lung cancer. However, based on conventional toxicity assessment systems, the carcinogenicity of asbestos and CNTs is unclear. The reason for late countermeasures against asbestos is that reliable, long-term safety assessments have not yet been developed by toxicologists. Therefore, a new type of long-term safety assessment, different from the existing methods, is needed for carbon nanomaterials. Recently, we applied a proteomic approach to the safety assessment of carbon nanomaterials. In this review, we discuss the basic concept of our approach, the results, the problems, and the possibility of a long-term safety assessment for carbon nanomaterials using the toxicoproteomic approach.}, } @article {pmid21404104, year = {2011}, author = {Zauderer, MG and Krug, LM}, title = {The evolution of multimodality therapy for malignant pleural mesothelioma.}, journal = {Current treatment options in oncology}, volume = {12}, number = {2}, pages = {163-172}, pmid = {21404104}, issn = {1534-6277}, support = {R25 CA020449/CA/NCI NIH HHS/United States ; T32 CA009207/CA/NCI NIH HHS/United States ; T32 CA009207-35/CA/NCI NIH HHS/United States ; }, mesh = {Combined Modality Therapy ; Humans ; Mesothelioma/drug therapy/radiotherapy/surgery/*therapy ; Pleural Neoplasms/drug therapy/radiotherapy/surgery/*therapy ; Treatment Outcome ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare neoplasm of the pleural surfaces that has been associated with asbestos exposure. MPM generally spreads locally along the ipsilateral pleura, especially at presentation, with distant metastatic disease typically seen only in the later stages of the disease course. As such, surgical resection and other local therapies have long been pursued as a primary form of treatment. Surgical options include debulking of the pleura by pleurectomy/decortication (P/D) or a more aggressive extrapleural pneumonectomy (EPP) which also involves removal of the lung, diaphragm, and involved pericardium. Even after major resection, MPM almost always recurs locally and has a poor prognosis. As such, many groups have pursued multimodality therapy, treating resectable patients with EPP, along with hemithoracic radiation to decrease the risk of local recurrence and chemotherapy to decrease the risk of distant metastatic disease. However, EPP is associated with significant morbidity and mortality, and many patients are not candidates for EPP due to underlying comorbid medical conditions. Additionally, many patients are unable to tolerate complete courses of adjuvant therapy after EPP. A large, multicenter retrospective analysis comparing EPP to P/D demonstrated better outcomes among those who underwent P/D. One challenge associated with P/D has been the delivery or radiation to the removed pleura with an intact lung. Yet, advances in radiation technique have allowed the exploration of high-dose radiation therapy after P/D. The ideal timing of chemotherapy relative to surgery and the role of intracavitary chemotherapy continue to be controversial issues. Clearly, MPM requires a multidisciplinary approach and, due to the myriad of open questions, much effort continues to focus on identifying the optimal combination of surgery, chemotherapy, and radiation.}, } @article {pmid21397972, year = {2011}, author = {Creaney, J and Yeoman, D and Musk, AW and de Klerk, N and Skates, SJ and Robinson, BW}, title = {Plasma versus serum levels of osteopontin and mesothelin in patients with malignant mesothelioma--which is best?.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {74}, number = {1}, pages = {55-60}, doi = {10.1016/j.lungcan.2011.02.007}, pmid = {21397972}, issn = {1872-8332}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*blood ; Blood Specimen Collection ; Female ; GPI-Linked Proteins/*blood ; Humans ; Lung Neoplasms/*diagnosis/pathology/physiopathology ; Male ; Mesothelin ; Mesothelioma/*diagnosis/pathology/physiopathology ; Middle Aged ; Osteopontin/*blood ; Plasma/metabolism ; Predictive Value of Tests ; Prognosis ; Sensitivity and Specificity ; Serum/metabolism ; }, abstract = {BACKGROUND: Blood-based markers for malignant mesothelioma (MM), particularly soluble mesothelin and osteopontin, are currently of great clinical interest. As there is some concern about the sensitivity of osteopontin in serum versus plasma, we compared them in the same patient population to mesothelin.

METHODS: Soluble mesothelin and osteopontin concentrations were determined by commercial assays in blood samples from 66 patients with pleural MM, 47 patients with non-malignant asbestos-related lung or pleural disease, 42 patients with other benign pleural and lung diseases and 21 patients with lung cancer.

RESULTS: Soluble mesothelin and osteopontin in serum and plasma were significantly elevated in MM patients compared to patients with benign lung and pleural disease. At a level of specificity of 95% relative to patients with benign disease, the sensitivity of mesothelin in serum and plasma at presentation with symptoms was 67%, and for osteopontin in the plasma was 40% and in the serum was 20% for MM patients. Combining the serum mesothelin and plasma osteopontin markers using a logistic regression model did not significantly increase the area under the receiver operator curve.

CONCLUSION: Plasma osteopontin has a superior diagnostic accuracy to serum. As the choice of blood sample type has limit effect on soluble mesothelin sensitivity, plasma should be collected for biomarker evaluation in patients suspected of having mesothelioma.}, } @article {pmid21394744, year = {2011}, author = {Bianchi, C and Bianchi, T}, title = {Mesothelioma and aircraft industry.}, journal = {American journal of industrial medicine}, volume = {54}, number = {6}, pages = {494}, doi = {10.1002/ajim.20949}, pmid = {21394744}, issn = {1097-0274}, mesh = {Aircraft/*statistics & numerical data ; Asbestos/*toxicity ; France/epidemiology ; Humans ; Industry/*statistics & numerical data ; Mesothelioma/*epidemiology/etiology ; Occupational Diseases/*epidemiology/etiology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/epidemiology/etiology ; Risk Factors ; }, } @article {pmid21383477, year = {2010}, author = {Chapman, EA and Thomas, PS and Yates, DH}, title = {Breath analysis in asbestos-related disorders: a review of the literature and potential future applications.}, journal = {Journal of breath research}, volume = {4}, number = {3}, pages = {034001}, doi = {10.1088/1752-7155/4/3/034001}, pmid = {21383477}, issn = {1752-7163}, mesh = {Asbestos/adverse effects/*analysis ; Asbestosis/*diagnosis ; Biomarkers ; Breath Tests ; Exhalation ; Humans ; }, abstract = {Asbestos usage was very common worldwide in the last century and continues in several countries today. Several diseases occur due to asbestos exposure, including malignant tumours such as malignant mesothelioma of the pleura and lung cancer, which have a very poor prognosis. Asbestos inhalation may also result in more benign conditions such as asbestosis (or pulmonary fibrosis due to asbestos), pleural plaques and pleural thickening. It is predicted that asbestos-associated mortality and morbidity will continue to increase, but methods for diagnosing asbestos-related disease are currently invasive and unsuitable for an increasingly elderly population. New non-invasive methods such as analysis of exhaled breath biomarkers e.g. exhaled nitric oxide (F(E)NO), exhaled breath condensate or of exhaled volatile organic compounds could potentially be extremely useful in these conditions. This article reviews the current literature on this topic and suggests areas for their application in the future.}, } @article {pmid21381365, year = {2010}, author = {Pylev, DN and Smirnova, OV and Vasil'eva, LA and Khrustalev, SA and Vezentsev, AI and Gudkova, EA and Naumova, LN}, title = {[Experimental rationale for carcinogenic risk of asbestos cement industry and its products].}, journal = {Gigiena i sanitariia}, volume = {}, number = {6}, pages = {61-65}, pmid = {21381365}, issn = {0016-9900}, mesh = {Animals ; Asbestos/*toxicity ; Carcinogens/*toxicity ; Construction Materials/*adverse effects ; Disease Models, Animal ; Dust ; Female ; *Industry ; Lung Neoplasms/*chemically induced/pathology ; Male ; Neoplasms, Experimental/*chemically induced/pathology ; Occupational Exposure/*adverse effects ; Rats ; Rats, Wistar ; Risk Factors ; }, abstract = {During intraperitoneal administration of dispersiveness-comparable chrysotile or asbestos cement fibers to rats (20 mg thrice), mesotheliomas were found in 45.1 and 7.7% of cases respectively. Asbestos cement dust induced tumors in 2.5% of cases, which is of biological importance. Cement or freeze asbestos destruction cement dust failed to cause tumors. The latter were not detected in a control group receiving physiological saline. Asbestos cement fibers and fascicles are covered by a cement matrix. Fiber amorphization gradually occurs. In lung tissue, there may be destruction of the cement coat of fascicles and release of native chrysotile fibers that are carcinogenic.}, } @article {pmid21375472, year = {2011}, author = {Maeda, R and Tabata, C and Tabata, R and Eguchi, R and Fujimori, Y and Nakano, T}, title = {Is serum thioredoxin-1 a useful clinical marker for malignant pleural mesothelioma?.}, journal = {Antioxidants & redox signaling}, volume = {15}, number = {3}, pages = {685-689}, doi = {10.1089/ars.2011.3978}, pmid = {21375472}, issn = {1557-7716}, mesh = {Adult ; Aged ; Asbestos/toxicity ; Biomarkers, Tumor/*blood ; Female ; Humans ; Male ; Mesothelioma/blood/chemically induced/*pathology ; Middle Aged ; Neoplasm Staging ; Pleural Neoplasms/blood/chemically induced/*pathology ; Prognosis ; Thioredoxins/*blood ; }, abstract = {Malignant pleural mesothelioma (MPM), an asbestos-related aggressive malignant tumor of mesothelial origin, shows limited response to therapy and overall survival remains very poor. Reactive oxygen species play an important role in asbestos toxicity. Here, we found that the patients with MPM had significantly higher serum levels of thioredoxin-1 (TRX) than control population. The patients with advanced-stage MPM showed higher levels of TRX than those with early-stage MPM. The difference in overall survival between the groups with lower and higher serum TRX levels was significant. Our data suggest that serum TRX concentration could be a useful clinical marker for MPM.}, } @article {pmid21358348, year = {2011}, author = {Hoda, MA and Mohamed, A and Ghanim, B and Filipits, M and Hegedus, B and Tamura, M and Berta, J and Kubista, B and Dome, B and Grusch, M and Setinek, U and Micksche, M and Klepetko, W and Berger, W}, title = {Temsirolimus inhibits malignant pleural mesothelioma growth in vitro and in vivo: synergism with chemotherapy.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {6}, number = {5}, pages = {852-863}, doi = {10.1097/JTO.0b013e31820e1a25}, pmid = {21358348}, issn = {1556-1380}, mesh = {Adenocarcinoma/*drug therapy/metabolism/pathology ; Animals ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Apoptosis/drug effects ; Blotting, Western ; Cell Cycle/drug effects ; Cell Proliferation/drug effects ; Cisplatin/administration & dosage ; Drug Synergism ; Feasibility Studies ; Female ; Humans ; Immunoenzyme Techniques ; In Situ Nick-End Labeling ; In Vitro Techniques ; Mesothelioma/*drug therapy/metabolism/pathology ; Mice ; Mice, SCID ; Pleural Neoplasms/*drug therapy/metabolism/pathology ; RNA, Messenger/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction ; Sirolimus/administration & dosage/analogs & derivatives ; Spheroids, Cellular ; Tumor Cells, Cultured ; Xenograft Model Antitumor Assays ; }, abstract = {INTRODUCTION: Human malignant pleural mesothelioma (MPM) is an asbestos-related malignancy characterized by frequent resistance to chemotherapy and radiotherapy. Here, we investigated the feasibility of mammalian target of rapamycin (mTOR) inhibition by temsirolimus as an antimesothelioma strategy.

METHODS: Phosphorylation of mTOR (p-mTOR) was assessed by immunohistochemistry in MPM surgical specimens (n = 70). Activation of mTOR and impact of mTOR inhibition by temsirolimus was determined in MPM cell lines in vitro (n = 6) and in vivo as xenografts in severe combined immunodeficiency mice (n = 2) either as single agent or in combination with cisplatin.

RESULTS: Strong immunoreactivity for p-mTOR was predominantly detected in epitheloid and biphasic but not sarcomatoid MPM specimens while adjacent normal tissues remained widely unstained. Accordingly, all mesothelioma cell lines harbored activated mTOR, which was further confirmed by hyperphosphorylation of the downstream targets pS6K, S6, and 4EBP1. Temsirolimus potently blocked mTOR-mediated signals and exerted a cytostatic effect on mesothelioma cell lines in vitro cultured both as adherent monolayers and as nonadherent spheroids. Mesothelioma cells with intrinsic or acquired cisplatin resistance exhibited hypersensitivity against temsirolimus. Accordingly, cisplatin and temsirolimus exerted synergistic inhibition of the mTOR downstream signals and enhanced growth inhibition and/or apoptosis induction in mesothelioma cell lines. Finally, temsirolimus was highly active against MPM xenograft models in severe combined immunodeficiency mice both as a single agent and in combination with cisplatin.

CONCLUSION: The mTOR inhibitor temsirolimus is active against mesothelioma in vitro and in vivo and synergizes with chemotherapy. These data suggest mTOR inhibition as a promising novel therapeutic strategy against MPM.}, } @article {pmid21358347, year = {2011}, author = {Balatti, V and Maniero, S and Ferracin, M and Veronese, A and Negrini, M and Ferrocci, G and Martini, F and Tognon, MG}, title = {MicroRNAs dysregulation in human malignant pleural mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {6}, number = {5}, pages = {844-851}, doi = {10.1097/JTO.0b013e31820db125}, pmid = {21358347}, issn = {1556-1380}, mesh = {Biomarkers, Tumor/*genetics/metabolism ; Blotting, Western ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Mesothelioma/*genetics/metabolism/pathology ; MicroRNAs/*physiology ; Pleural Neoplasms/*genetics/metabolism/pathology ; RNA, Messenger/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare but aggressive asbestos-related cancer that develops by mesothelial cell transformation. At present, there are no effective therapies for MPM. Great efforts have been made in finding specific markers/mechanisms for MPM onset, including studies into microRNAs (miRNAs). Recent studies have shown the differential expression of mature miRNAs in several human cancers, suggesting their potential role as oncogenes or tumor suppressor genes.

METHODS: In this study, we investigated miRNAs profile in five human normal pleural mesothelial short-term cell cultures (HMCs) and five MPMs, with microarray approach. These results were confirmed by real-time quantitative reverse-transcriptase polymerase chain reaction and Western blotting.

RESULTS: A comparative analysis of miRNA expression in MPM and HMCs was carried out. Microarray profiling showed different miRNA expression between MPM and HMCs. Specifically, members of the oncomiRNA miR 17-92 cluster and its paralogs, namely miR 17-5p, 18a, 19b, 20a, 20b, 25, 92, 106a, 106b, were markedly upregulated. Besides, in our investigation, additional miRNAs, such as miR-7, miR-182, miR-214, and miR-497 were found to be dysregulated in MPM.

CONCLUSIONS: These data are in agreement with results that have previously been reported on dysregulated miRNAs for other solid human tumors. Moreover, in our investigation, additional miRNAs were found to be dysregulated in MPM. Interestingly, gene products that regulate the cell cycle are targets and predicted targets for these miRNAs. Our data suggest that specific miRNAs could be key players in MPM development/progression. In addition, some of these miRNAs may represent MPM markers and potential targets for new therapeutic approaches.}, } @article {pmid21358346, year = {2011}, author = {Hollevoet, K and Van Cleemput, J and Thimpont, J and De Vuyst, P and Bosquée, L and Nackaerts, K and Germonpré, P and Vansteelandt, S and Kishi, Y and Delanghe, JR and van Meerbeeck, JP}, title = {Serial measurements of mesothelioma serum biomarkers in asbestos-exposed individuals: a prospective longitudinal cohort study.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {6}, number = {5}, pages = {889-895}, doi = {10.1097/JTO.0b013e31820db377}, pmid = {21358346}, issn = {1556-1380}, mesh = {Aged ; Asbestos/*adverse effects ; Biomarkers, Tumor/*blood ; Cohort Studies ; Female ; Follow-Up Studies ; GPI-Linked Proteins/*blood ; Glomerular Filtration Rate ; Humans ; Longitudinal Studies ; Male ; Mesothelin ; Mesothelioma/blood/*diagnosis ; Middle Aged ; Occupational Exposure/adverse effects ; Pleural Neoplasms/blood/*diagnosis ; Prognosis ; Prospective Studies ; }, abstract = {INTRODUCTION: Soluble mesothelin (SM) and megakaryocyte potentiating factor (MPF) are serum biomarkers of mesothelioma. This study aims to examine the longitudinal behavior of SM and MPF in controls to gain insight in the optimal use of these biomarkers in screening.

METHODS: Asbestos-exposed individuals, with no malignant disease at inclusion, were surveilled for 2 years with annual measurements of SM and MPF. Fixed thresholds were set at 2.10 nmol/L for SM and 13.10 ng/ml for MPF. Longitudinal biomarker analysis, using a random intercept model, estimated the association with age and glomerular filtration rate (GFR), and the intraclass correlation. The latter represents the proportion of total biomarker variance accounted for by the between-individual variance.

RESULTS: A total of 215 participants were included, of whom 179 and 137 provided a second sample and third sample, respectively. Two participants with normal SM and MPF levels presented afterward with mesothelioma and lung cancer, respectively. Participants with elevated biomarker levels were typically older and had a lower GFR. During follow-up, biomarker levels significantly increased. Longitudinal analysis indicated that this was in part due to aging, while changes in GFR had a less pronounced effect on serial biomarker measurements. SM and MPF had a high intraclass correlation of 0.81 and 0.78, respectively, which implies that a single biomarker measurement and fixed threshold are suboptimal in screening.

CONCLUSIONS: The longitudinal behavior of SM and MPF in controls indicates that a biomarker-based screening approach can benefit from the incorporation of serial measurements and individual-specific screening rules, adjusted for age and GFR. Large-scale validation remains nevertheless mandatory to elucidate whether such an approach can improve the early detection of mesothelioma.}, } @article {pmid21357438, year = {2011}, author = {Maeda, M and Nishimura, Y and Hayashi, H and Kumagai, N and Chen, Y and Murakami, S and Miura, Y and Hiratsuka, J and Kishimoto, T and Otsuki, T}, title = {Decreased CXCR3 expression in CD4+ T cells exposed to asbestos or derived from asbestos-exposed patients.}, journal = {American journal of respiratory cell and molecular biology}, volume = {45}, number = {4}, pages = {795-803}, doi = {10.1165/rcmb.2010-0435OC}, pmid = {21357438}, issn = {1535-4989}, mesh = {Adult ; Apoptosis/drug effects ; Asbestos, Serpentine/*toxicity ; Asbestosis/*etiology/genetics/immunology/pathology ; CD4-Positive T-Lymphocytes/*drug effects/immunology/pathology ; Case-Control Studies ; Cell Line, Tumor ; Chemokine CXCL10/blood ; Construction Materials/*toxicity ; Dose-Response Relationship, Drug ; Down-Regulation ; Female ; Humans ; Interferon-gamma/genetics/metabolism ; Lung Neoplasms/*chemically induced/genetics/immunology/pathology ; Male ; Mesothelioma/*chemically induced/genetics/immunology/pathology ; Middle Aged ; RNA, Messenger/metabolism ; Receptors, CXCR3/*metabolism ; Time Factors ; Tumor Escape/*drug effects ; }, abstract = {Asbestos causes malignant tumors such as lung cancer and malignant mesothelioma (MM). To determine whether asbestos exposure causes reduction of antitumor immunity, we established an in vitro T-cell line model of low-dose and continuous exposure to asbestos using an human adult T-cell leukemia virus-1 immortalized human polyclonal T-cell line, MT-2, and revealed that MT-2 cells exposed continuously to asbestos showed resistance to asbestos-induced apoptosis. In addition, the cells presented reduction of surface CXCR3 chemokine receptor expression and IFN-γ production. In this study, to confirm that these findings are suitable for clinical translation, surface CXCR3 and IFN-γ expression were analyzed using freshly isolated human CD4(+) T cells derived from healthy donors and patients with pleural plaque (PP) or MM. The results revealed that CXCR3 and IFN-γ expression in the ex vivo model were reduced in some cases. Additionally, CXCR3 expression in CD4(+) T cells from PPs and MMs was significantly reduced compared with that from healthy donors, and CD4(+) T cells from patients with MMs exhibited a marked reduction in IFN-γ mRNA levels after stimulation in vitro. Moreover, CD4(+)CXCR3(+) T cells in lymphocytes from MMs showed a tendency for an inverse correlation with its ligand CXCL10/IP10 in plasma. These findings show reduction of antitumor immune function in asbestos-exposed patients and indicate that CXCR3, IFN-γ, and CXCL10/IP10 may be candidates to detect and monitor disease status.}, } @article {pmid21353903, year = {2011}, author = {Bridle, J and Hoskins, J}, title = {Canadian hypocrisy regarding chrysotile.}, journal = {Lancet (London, England)}, volume = {377}, number = {9767}, pages = {720}, doi = {10.1016/S0140-6736(11)60271-7}, pmid = {21353903}, issn = {1474-547X}, mesh = {Asbestos, Serpentine/*adverse effects ; Canada ; *Carcinogens ; Environmental Exposure/*adverse effects ; Humans ; Lung Neoplasms/chemically induced/*etiology ; Mesothelioma/chemically induced/*etiology ; Occupational Exposure/adverse effects ; Societies, Medical ; United Kingdom ; World Health Organization ; }, } @article {pmid21351265, year = {2010}, author = {Gee, GV and Koestler, DC and Christensen, BC and Sugarbaker, DJ and Ugolini, D and Ivaldi, GP and Resnick, MB and Houseman, EA and Kelsey, KT and Marsit, CJ}, title = {Downregulated microRNAs in the differential diagnosis of malignant pleural mesothelioma.}, journal = {International journal of cancer}, volume = {127}, number = {12}, pages = {2859-2869}, pmid = {21351265}, issn = {1097-0215}, support = {1-U19-OH009077-01/OH/NIOSH CDC HHS/United States ; R01 CA126939-02/CA/NCI NIH HHS/United States ; U19 OH009077/OH/NIOSH CDC HHS/United States ; P20 RR015578/RR/NCRR NIH HHS/United States ; T32 ES007272-11/ES/NIEHS NIH HHS/United States ; T32 ES007272-17/ES/NIEHS NIH HHS/United States ; P50RR015578/RR/NCRR NIH HHS/United States ; R01CA126939/CA/NCI NIH HHS/United States ; R01 CA126939/CA/NCI NIH HHS/United States ; P20 RR015578-07/RR/NCRR NIH HHS/United States ; T32 ES007272/ES/NIEHS NIH HHS/United States ; T32ES007272/ES/NIEHS NIH HHS/United States ; }, mesh = {Adenocarcinoma/*diagnosis/genetics ; Biomarkers, Tumor/*genetics ; Diagnosis, Differential ; Down-Regulation ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/*diagnosis/genetics ; Mesothelioma/*diagnosis/genetics ; MicroRNAs/*genetics ; Oligonucleotide Array Sequence Analysis ; Pleural Neoplasms/*diagnosis/genetics ; Prognosis ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rapidly fatal disease whose diagnosis, particularly through less invasive techniques such as analysis of pleural effusion, can be challenging. Currently, a commercially available diagnostic test based on microRNA (miRNA) expression patterns is purported to distinguish between mesothelioma and lung adenocarcinoma. Yet, the biological basis of this technology has not been reported in the literature, and little research has been aimed at determining how differential miRNA expression contributes to the differences in pathogenesis between these diseases, both of which can be caused by asbestos exposure. We sought to illuminate the molecular differences between mesothelioma and lung adenocarcinoma by using miRNA microarrays to identify patterns in the most differentially expressed miRNAs. From this, we identified a panel of miRNAs, including members of the miR-200 gene family, that were all downregulated in MPM compared to lung adenocarcinoma. Using the more sensitive detection method of quantitative RT-PCR on an independent series of tumors, we validated the specificity of these alterations in 100 MPMs and 32 lung adenocarcinomas. Statistical analysis reveals that these miRNAs exceed the current recommendations for biomarkers and could greatly aid in the differential diagnosis. Further examination led us to predict that they act as redundant regulators of wnt signaling and suggests a role for this pathway in tumor progression. This research points to novel approaches using miRNAs whose decreased expression is unique to mesothelioma as potentially suitable for rapid diagnosis and reveals prospective new targets for the treatment of this deadly disease.}, } @article {pmid21346295, year = {2011}, author = {Metz-Flamant, C and Guseva Canu, I and Laurier, D}, title = {Malignant pleural mesothelioma risk among nuclear workers: a review.}, journal = {Journal of radiological protection : official journal of the Society for Radiological Protection}, volume = {31}, number = {1}, pages = {9-23}, doi = {10.1088/0952-4746/31/1/R01}, pmid = {21346295}, issn = {1361-6498}, mesh = {Humans ; Mesothelioma/*epidemiology ; Neoplasms, Radiation-Induced/*epidemiology ; Nuclear Reactors/*statistics & numerical data ; Occupational Diseases/*epidemiology ; Occupational Exposure/*statistics & numerical data ; Pleural Neoplasms/*epidemiology ; Prevalence ; Radiation Dosage ; Radiation Monitoring/*statistics & numerical data ; Risk Assessment ; Risk Factors ; }, abstract = {Exposure to ionising radiation has been suggested as a causal risk factor for malignant pleural mesothelioma (MPM). Studies of patients treated by radiotherapy for primary cancers have suggested that radiation contributes to the development of secondary MPM. Here we examined the risk to nuclear workers of MPM related to exposure to low doses of occupational radiation at low dose rates. All results concerning MPM risk in published studies of nuclear workers were examined for their association with radiation exposure and potential confounders. We found 19 relevant studies. Elevated risks of pleural cancer were reported in most (15/17) of these studies. Eight reported risks higher for radiation monitored workers than for other workers. However, of 12 studies that looked at associations with ionising radiation, only one reported a significant dose-risk association. Asbestos was an important confounder in most studies. We conclude that studies of nuclear workers have not detected an association between ionising radiation exposure and MPM. Further investigations should improve the consideration of asbestos exposure at the same time as they address the risk of MPM related to occupational exposure of nuclear workers to low doses of ionising radiation at low dose rates.}, } @article {pmid21344825, year = {2011}, author = {Donaldson, K and Oberdörster, G}, title = {Continued controversy on chrysotile biopersistence.}, journal = {International journal of occupational and environmental health}, volume = {17}, number = {1}, pages = {98-9; discussion 99-102}, doi = {10.1179/107735211799031121}, pmid = {21344825}, issn = {1077-3525}, mesh = {Asbestos, Serpentine/*chemistry/*pharmacokinetics ; Biological Availability ; Environmental Exposure/*adverse effects ; Humans ; Lung/metabolism ; Lung Neoplasms/*chemically induced/metabolism ; Mesothelioma/*chemically induced/metabolism ; Occupational Exposure/adverse effects ; }, } @article {pmid21340132, year = {2010}, author = {Marsili, D and Comba, P and Bruno, C and Calisti, R and Marinaccio, A and Mirabelli, D and Papa, L and Harari, R}, title = {[Preventing asbestos-related diseases: operative action for Italian cooperation with Latin-American countries].}, journal = {Revista de salud publica (Bogota, Colombia)}, volume = {12}, number = {4}, pages = {682-692}, doi = {10.1590/s0124-00642010000400014}, pmid = {21340132}, issn = {2539-3596}, mesh = {Air Pollutants, Occupational/adverse effects ; Asbestos/*adverse effects ; Asbestosis/*prevention & control ; Carcinogens, Environmental/*adverse effects ; Construction Materials ; Environmental Exposure/prevention & control ; Humans ; *International Cooperation ; Italy ; Latin America ; Mesothelioma/diagnosis/etiology/*prevention & control ; Occupational Exposure/prevention & control ; Pleural Neoplasms/diagnosis/etiology/*prevention & control ; Population Surveillance ; Workers' Compensation ; }, abstract = {The present paper was aimed at promoting countermeasures based on scientific evidence and international cooperation for evaluating the impact on health caused by exposure to asbestos fibres in the workplace and the environment. Scientific evidence regarding asbestos made available by the international scientific community, decades of experience gained in Italy on this issue and being aware that adopting measures to combat the health effects caused by asbestos exposure should be verified considering the specificity of various national and local contexts in Latin-America form the basis for identifying four main areas for intervention which may be developed in the field of technical and scientific cooperation between Italy and Latin-America countries: promoting access to information about asbestos, interventions for reducing exposure to asbestos, health surveillance of exposed subjects and mesothelioma detection. Integrating Colombian and Italian researchers' abilities may lead to such results being achieved, thereby contributing to banning asbestos, which is already underway in Latin-America.}, } @article {pmid21333373, year = {2011}, author = {Boudville, N and Paul, R and Robinson, BW and Creaney, J}, title = {Mesothelin and kidney function--analysis of relationship and implications for mesothelioma screening.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {73}, number = {3}, pages = {320-324}, doi = {10.1016/j.lungcan.2011.01.011}, pmid = {21333373}, issn = {1872-8332}, mesh = {Aged ; Aged, 80 and over ; *Biomarkers, Tumor/blood/urine ; *Creatinine/blood/urine ; Cross-Sectional Studies ; Diagnosis, Differential ; Disease Progression ; Female ; *GPI-Linked Proteins/blood/urine ; Humans ; Kidney Failure, Chronic/*diagnosis/physiopathology ; Male ; Mass Screening ; Mesothelin ; Mesothelioma/*diagnosis/physiopathology ; Middle Aged ; }, abstract = {PURPOSE: Malignant mesothelioma (MM) carries a poor prognosis and remains a major public health issue in many countries. Outcomes may be improved with earlier detection and this justifies screening the at-risk asbestos-exposed population. Soluble mesothelin is a potential biomarker for MM, but it has been observed to be elevated in patients with reduced kidney function. Defining the relationship between mesothelin concentrations and kidney function will allow more accurate interpretation of this assay.

MATERIALS AND METHODS: A cross-sectional study consisting of 144 patients with chronic kidney disease (CKD) was conducted at Sir Charles Gairdner Hospital and Royal Perth Hospital in Western Australia. Only patients with CKD stages II-V were recruited while those with a history of renal transplant, dialysis, or malignancy were excluded. Serum and urine mesothelin and creatinine concentrations were determined.

RESULTS: There were 33, 49, 31 and 31 patients in CKD stages II, III, IV and V, respectively recruited. Serum mesothelin increased significantly with increasing serum creatinine (p<0.0001), and worsening stage of CKD (p<0.0001). A significant correlation between urine mesothelin to creatinine ratio and serum mesothelin concentration was detected (p=0.002). No significant difference was found in urine mesothelin to creatinine ratios across the four CKD stage groups.

CONCLUSION: Serum mesothelin concentration is elevated in individuals with renal impairment. Renal function should therefore be taken into account during interpretation of this assay.}, } @article {pmid21309996, year = {2011}, author = {Jamrozik, E and de Klerk, N and Musk, AW}, title = {Asbestos-related disease.}, journal = {Internal medicine journal}, volume = {41}, number = {5}, pages = {372-380}, doi = {10.1111/j.1445-5994.2011.02451.x}, pmid = {21309996}, issn = {1445-5994}, mesh = {Air Pollutants/adverse effects ; Asbestos/*adverse effects ; Asbestos, Serpentine/adverse effects ; Asbestosis/epidemiology/etiology ; Australia/epidemiology ; Environmental Exposure ; Forecasting ; Humans ; Lung Neoplasms/etiology ; Mesothelioma/epidemiology/etiology ; Mineral Fibers/adverse effects ; Mining ; Occupational Diseases/epidemiology/etiology ; Occupational Exposure ; Peritoneal Neoplasms/epidemiology/etiology ; Pleural Diseases/epidemiology/etiology ; Pleural Neoplasms/epidemiology/etiology ; Pulmonary Atelectasis/etiology ; Workers' Compensation/legislation & jurisprudence ; }, abstract = {Inhalation of airborne asbestos fibres causes several diseases. These include asbestosis, lung cancer, malignant mesothelioma as well as pleural effusion, discrete (plaques) or diffuse benign pleural fibrosis and rolled atelectasis. The lag time between exposure and the development of disease may be many decades, thus the health risks of asbestos continue to be relevant despite bans on the use of asbestos and improvements in safety regulations for those who are still exposed. Asbestos was mined and used extensively in Australia for over 100 years and Australia is now experiencing part of a worldwide epidemic of asbestos-related disease. This review provides insight into the history and epidemiology of asbestos-related disease in Australia and discusses relevant clinical aspects in their diagnosis and management. The past and current medico-legal aspects of asbestos as well as currently evolving areas of research and future projections are summarized.}, } @article {pmid21306408, year = {2011}, author = {Berman, DW}, title = {Apples to apples: the origin and magnitude of differences in asbestos cancer risk estimates derived using varying protocols.}, journal = {Risk analysis : an official publication of the Society for Risk Analysis}, volume = {31}, number = {8}, pages = {1308-1326}, doi = {10.1111/j.1539-6924.2010.01581.x}, pmid = {21306408}, issn = {1539-6924}, mesh = {Asbestos/administration & dosage/*adverse effects/chemistry ; Dust ; Humans ; Inhalation Exposure ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Neoplasms/*etiology ; Particle Size ; Risk Assessment/methods/statistics & numerical data ; Risk Factors ; }, abstract = {Given that new protocols for assessing asbestos-related cancer risk have recently been published, questions arise concerning how they compare to the "IRIS" protocol currently used by regulators. The newest protocols incorporate findings from 20 additional years of literature. Thus, differences between the IRIS and newer Berman and Crump protocols are examined to evaluate whether these protocols can be reconciled. Risks estimated by applying these protocols to real exposure data from both laboratory and field studies are also compared to assess the relative health protectiveness of each protocol. The reliability of risks estimated using the two protocols are compared by evaluating the degree with which each potentially reproduces the known epidemiology study risks. Results indicate that the IRIS and Berman and Crump protocols can be reconciled; while environment-specific variation within fiber type is apparently due primarily to size effects (not addressed by IRIS), the 10-fold (average) difference between amphibole asbestos risks estimated using each protocol is attributable to an arbitrary selection of the lowest of available mesothelioma potency factors in the IRIS protocol. Thus, the IRIS protocol may substantially underestimate risk when exposure is primarily to amphibole asbestos. Moreover, while the Berman and Crump protocol is more reliable than the IRIS protocol overall (especially for predicting amphibole risk), evidence is presented suggesting a new fiber-size-related adjustment to the Berman and Crump protocol may ultimately succeed in reconciling the entire epidemiology database. However, additional data need to be developed before the performance of the adjusted protocol can be fully validated.}, } @article {pmid21302609, year = {2010}, author = {Hmeljak, J and Kern, I and Cör, A}, title = {No implication of Simian virus 40 in pathogenesis of malignant pleural mesothelioma in Slovenia.}, journal = {Tumori}, volume = {96}, number = {5}, pages = {667-673}, doi = {10.1177/030089161009600504}, pmid = {21302609}, issn = {0300-8916}, mesh = {Antigens, Viral, Tumor/*analysis ; DNA, Viral/isolation & purification ; Humans ; Immunohistochemistry ; Mesothelioma/*epidemiology/virology ; Pleural Neoplasms/*epidemiology/virology ; Polymerase Chain Reaction ; Simian virus 40/genetics/immunology/*isolation & purification ; Slovenia/epidemiology ; }, abstract = {BACKGROUND AND AIM: Malignant mesothelioma is predominantly caused by asbestos exposure, although the association of Simian virus 40 in its pathogenesis is currently still under debate. Simian virus 40, a DNA rhesus monkey virus with oncogenic properties, accidentally contaminated early batches of polio vaccine in the 1960s. In the 1990s, viral sequences and proteins were discovered in several human tumors, which triggered research to find a link between Simian virus 40 and human cancers, especially malignant mesothelioma. The aim of our study was to establish an effective laboratory procedure for Simian virus 40 detection and to investigate the presence of Simian virus 40 DNA and small t antigen in mesothelioma samples from Slovenian patients.

METHODS AND STUDY DESIGN: Paraffin-embedded malignant pleural mesothelioma specimens from 103 Slovenian patients were collected and used for total DNA isolation and real-time polymerase chain reaction for Simian virus 40 small t and large T DNA analysis. Special attention was devoted to primer design, good laboratory practice and polymerase chain reaction contamination prevention. Polymerase chain reaction products were sequenced and BLAST aligned. One 5 microm thick paraffin section from each patient's tissue block was stained with hematoxylin and eosin for histological typing and one for immunohistochemical detection of Simian virus 40 small t antigen using a monoclonal antibody against Simian virus 40 (Pab280). SV40-expressing Wi-38 cells were used as positive control in both PCR and immunohistochemistry.

RESULTS: In real-time polymerase chain reaction analyses, only 4 samples gave products with primer pairs amplifying small t antigen and were inconsistent and poorly reproducible. BLAST alignment showed no homology with any deposited SV40 sequences. No immunopositive staining for SV40 small t antigen was found in any of the samples.

CONCLUSIONS: We found no evidence of SV40 presence in tissue samples from 103 Slovenian patients with malignant pleural mesothelioma. Asbestos exposure remains the main risk factor for malignant pleural mesothelioma in Slovenia.}, } @article {pmid21288646, year = {2011}, author = {Zucali, PA and Ceresoli, GL and De Vincenzo, F and Simonelli, M and Lorenzi, E and Gianoncelli, L and Santoro, A}, title = {Advances in the biology of malignant pleural mesothelioma.}, journal = {Cancer treatment reviews}, volume = {37}, number = {7}, pages = {543-558}, doi = {10.1016/j.ctrv.2011.01.001}, pmid = {21288646}, issn = {1532-1967}, mesh = {Antineoplastic Agents/*therapeutic use ; Clinical Trials as Topic ; Humans ; Mesothelioma/drug therapy/*metabolism/pathology ; Neoplasm Proteins/*metabolism ; Pleural Effusion, Malignant/drug therapy/*metabolism/pathology ; Pleural Neoplasms/drug therapy/*metabolism/pathology ; Signal Transduction/*drug effects ; }, abstract = {Malignant pleural mesothelioma is a highly aggressive cancer with a very poor prognosis. Although the mechanism of carcinogenesis is not fully understood, approximately 80% of malignant pleural mesothelioma can be attributed to asbestos fiber exposure. This disease is largely unresponsive to conventional chemotherapy or radiotherapy, and most patients die within 10-17 months of their first symptoms. Currently, malignant pleural mesothelioma therapy is guided by clinical stage and patient characteristics rather than by the histological or molecular features of the tumor. Several molecular pathways involved in malignant pleural mesothelioma have been identified; these include cell cycle regulation, apoptosis, growth factor pathways, and angiogenesis. Unfortunately, several agents targeting these processes, including erlotinib, gefitinib, and imatinib, have proven ineffective in clinical trials. A greater understanding of the molecular pathways involved in malignant pleural mesothelioma is needed to develop better diagnostics, therapeutics, and preventative measures. Moreover, understanding the biological basis of mesothelioma progression may facilitate personalized treatment approaches, and early identification of poor prognostic indicators may help reduce the heterogeneity of the clinical response. This paper reviews advances in the molecular biology of malignant pleural mesothelioma in terms of pathogenesis, the major molecular pathways and the associated therapeutic strategies, and the roles of biomarkers.}, } @article {pmid21281830, year = {2011}, author = {Fuhrer, G and Lazarus, AA}, title = {Mesothelioma.}, journal = {Disease-a-month : DM}, volume = {57}, number = {1}, pages = {40-54}, doi = {10.1016/j.disamonth.2010.12.004}, pmid = {21281830}, issn = {1557-8194}, mesh = {Asbestos/*adverse effects ; Humans ; Inhalation Exposure/*adverse effects ; Mesothelioma/*diagnosis/etiology/therapy ; Pleural Neoplasms/*diagnosis/etiology/therapy ; Prognosis ; }, } @article {pmid21281820, year = {2011}, author = {Jean, D and Thomas, E and Manié, E and Renier, A and de Reynies, A and Lecomte, C and Andujar, P and Fleury-Feith, J and Galateau-Sallé, F and Giovannini, M and Zucman-Rossi, J and Stern, MH and Jaurand, MC}, title = {Syntenic relationships between genomic profiles of fiber-induced murine and human malignant mesothelioma.}, journal = {The American journal of pathology}, volume = {178}, number = {2}, pages = {881-894}, pmid = {21281820}, issn = {1525-2191}, mesh = {Aged ; Alleles ; Animals ; Asbestos/*adverse effects ; Chromosomes, Human/genetics ; Comparative Genomic Hybridization ; Female ; Gene Deletion ; Genetic Association Studies ; Genome/*genetics ; Genomic Instability/genetics ; *Genomics ; Humans ; Male ; Mesothelioma/*genetics/pathology ; Mice ; Middle Aged ; Mutation/genetics ; Pleural Neoplasms/*genetics/pathology ; Synteny/*genetics ; Xenograft Model Antitumor Assays ; }, abstract = {Malignant mesothelioma (MM) is an aggressive tumor with a poor prognosis mainly linked to past asbestos exposure. Murine models of MM based on fiber exposure have been developed to elucidate the mechanism of mesothelioma formation. Genomic alterations in murine MM have now been partially characterized. To gain insight into the pathophysiology of mesothelioma, 16 murine and 35 human mesotheliomas were characterized by array-comparative genomic hybridization and were screened for common genomic alterations. Alteration of the 9p21 human region, often by biallelic deletion, was the most frequent alteration in both species, in agreement with the CDKN2A/CDKN2B locus deletion in human disease and murine models. Other shared aberrations were losses of 1p36.3-p35 and 13q14-q33 and gains of 5p15.3-p13 regions. However, some differences were noted, such as absence of recurrent alterations in mouse regions corresponding to human chromosome 22. Comparison between altered recurrent regions in asbestos-exposed and non-asbestos-exposed patients showed a significant difference in the 14q11.2-q21 region, which was also lost in fiber-induced murine mesothelioma. A correlation was also demonstrated between genomic instability and tumorigenicity of human mesothelioma xenografts in nude mice. Overall, these data show similarities between murine and human disease, and contribute to the understanding of the influence of fibers in the pathogenesis of mesothelioma and validation of the murine model for preclinical testing.}, } @article {pmid21277872, year = {2011}, author = {Betti, M and Ferrante, D and Padoan, M and Guarrera, S and Giordano, M and Aspesi, A and Mirabelli, D and Casadio, C and Ardissone, F and Ruffini, E and Betta, PG and Libener, R and Guaschino, R and Matullo, G and Piccolini, E and Magnani, C and Dianzani, I}, title = {XRCC1 and ERCC1 variants modify malignant mesothelioma risk: a case-control study.}, journal = {Mutation research}, volume = {708}, number = {1-2}, pages = {11-20}, doi = {10.1016/j.mrfmmm.2011.01.001}, pmid = {21277872}, issn = {0027-5107}, mesh = {Asbestos/toxicity ; Base Sequence ; Case-Control Studies ; DNA-Binding Proteins/*genetics ; Endonucleases/*genetics ; Female ; Genetic Predisposition to Disease ; Humans ; Male ; Mesothelioma/*genetics ; Middle Aged ; *Polymorphism, Single Nucleotide ; Risk Factors ; X-ray Repair Cross Complementing Protein 1 ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare aggressive tumor associated with asbestos exposure. The possible role of genetic factors has also been suggested and MPM has been associated with single nucleotide polymorphisms (SNPs) of xenobiotic and oxidative metabolism enzymes. We have identified an association of the DNA repair gene XRCC1 with MPM in the population of Casale Monferrato, a town exposed to high asbestos pollution. To extend this observation we examined 35 SNPs in 15 genes that could be involved in MPM carcinogenicity in 220 MPM patients and 296 controls from two case-control studies conducted in Casale (151 patients, 252 controls) and Turin (69 patients, 44 controls), respectively. Unconditional multivariate logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). Two DNA repair genes were associated with MPM, i.e. XRCC1 and ERCC1. Considering asbestos-exposed only, the risk increased with the increasing number of XRCC1-399Q alleles (Casale: OR=1.44, 95%CI 1.02-2.03; Casale+Turin: OR=1.34, 95%CI 0.98-1.84) or XRCC1 -77T alleles (Casale+Turin: OR=1.33, 95%CI 0.97-1.81). The XRCC1-TGGGGGAACAGA haplotype was significantly associated with MPM (Casale: OR=1.76, 95%CI 1.04-2.96). Patients heterozygotes for ERCC1 N118N showed an increased OR in all subjects (OR=1.66, 95%CI 1.06-2.60) and in asbestos-exposed only (OR=1.59, 95%CI 1.01-2.50). When the dominant model was considered (i.e. ERCC1 heterozygotes CT plus homozygotes CC versus homozygotes TT) the risk was statistically significant both in all subjects (OR=1.61, 95%CI 1.06-2.47) and in asbestos-exposed only (OR=1.56, 95%CI 1.02-2.40). The combination of ERCC1 N118N and XRCC1 R399Q was statistically significant (Casale: OR=2.02, 95%CI 1.01-4.05; Casale+Turin: OR=2.39, 95%CI 1.29-4.43). The association of MPM with DNA repair genes support the hypothesis that an increased susceptibility to DNA damage may favour asbestos carcinogenicity.}, } @article {pmid21266919, year = {2011}, author = {Kao, SC and Yan, TD and Lee, K and Burn, J and Henderson, DW and Klebe, S and Kennedy, C and Vardy, J and Clarke, S and van Zandwijk, N and McCaughan, BC}, title = {Accuracy of diagnostic biopsy for the histological subtype of malignant pleural mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {6}, number = {3}, pages = {602-605}, doi = {10.1097/JTO.0b013e31820ce2c7}, pmid = {21266919}, issn = {1556-1380}, mesh = {Adult ; Aged ; Female ; Follow-Up Studies ; Humans ; Male ; Mesothelioma/*classification/*diagnosis/surgery ; Middle Aged ; Neoplasm Staging ; Pleural Neoplasms/*classification/*diagnosis/surgery ; Pneumonectomy ; Prognosis ; Retrospective Studies ; Sensitivity and Specificity ; Survival Rate ; Thoracoscopy ; Thoracotomy ; Tomography, X-Ray Computed ; Young Adult ; }, abstract = {INTRODUCTION: Histological subtype is an established prognostic factor in malignant pleural mesothelioma (MPM). We retrospectively investigated the accuracy of classifying histological subtype on diagnostic biopsies and examined the impact of different diagnostic procedures on the outcome.

METHODS: Consecutive patients with histologically confirmed MPM who underwent extrapleural pneumonectomy (EPP) from 1994 to 2009 were included. Patient records were reviewed, and the initial diagnoses of histological subtype were obtained. The archival EPP specimens were reviewed by a panel of pathologists. The histological subtype obtained at review was compared with the initial diagnosis.

RESULTS: Eighty-five patients underwent EPP. Two patients achieved a pathological complete response after neoadjuvant chemotherapy, leaving 83 patients to be included in this review. Different diagnostic methods were used before EPP: 81% thoracoscopy; 7% thoracotomy; 11% computed tomography-guided procedure; and 1% other. Patients determined to have an epithelial subtype (n = 64) at EPP were diagnosed correctly at initial diagnostic biopsy in 84% of cases, whereas patients considered to have a biphasic subtype (n = 19) at EPP were diagnosed correctly at diagnostic biopsy in 26% of cases. The sensitivity and specificity of diagnostic biopsy for epithelial MPM was 93% and 31%, respectively. The overall subtype misclassification rate was 20%. Biopsy by thoracotomy was most accurate in subtype classification (83%) compared with thoracoscopy (74%) and computed tomography-guided procedure (44%).

CONCLUSIONS: The determination of histological subtype from a diagnostic biopsy is difficult due to sampling error, but an adequate specimen obtained from surgical biopsy increases the accuracy of subtype classification compared with radiological-guided biopsies.}, } @article {pmid21263312, year = {2011}, author = {Greillier, L and Marco, S and Barlesi, F}, title = {Targeted therapies in malignant pleural mesothelioma: a review of clinical studies.}, journal = {Anti-cancer drugs}, volume = {22}, number = {3}, pages = {199-205}, doi = {10.1097/CAD.0b013e328341ccdd}, pmid = {21263312}, issn = {1473-5741}, mesh = {Angiogenesis Inhibitors/*therapeutic use ; Antineoplastic Agents/*therapeutic use ; Asbestos/*adverse effects ; Clinical Trials as Topic ; Histone Deacetylase Inhibitors/therapeutic use ; Humans ; Mesothelioma/*drug therapy/etiology/pathology/therapy ; *Molecular Targeted Therapy ; Pleural Neoplasms/*drug therapy/etiology/pathology/therapy ; Prognosis ; Protein Kinase Inhibitors/*therapeutic use ; Signal Transduction ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive tumor with poor prognosis, whose exposure to asbestos fibers is the main etiology. The incidence of MPM is anticipated to increase worldwide during the first half of this century. MPM is notoriously refractory to most treatments, and the only standard of care is cisplatin and antifolate first-line chemotherapy. The urgent need for additional therapeutic agents, in parallel with advances in the knowledge of the molecular events of oncogenesis, has resulted in the development of the so-called 'targeted agents' that specifically inhibit critical pathways in malignant cells and in their microenvironment. We carried out a comprehensive review of the literature from January 2000 to May 2010 on studies that assessed targeted agents for the systemic treatment of MPM. Although tyrosine kinase inhibitors directed against the epidermal growth factor and the platelet-derived growth factor receptors did not show significant clinical activity in phase II studies, some other targeted therapies seemed promising, notably histone deacetylase inhibitors and antiangiogenic agents. However, none of these has yet reached daily practice. That is the reason why efforts must continue in the area of clinical and translational research for MPM.}, } @article {pmid21258597, year = {2010}, author = {Lee, HE and Kim, HR}, title = {Occupational respiratory cancer in Korea.}, journal = {Journal of Korean medical science}, volume = {25}, number = {Suppl}, pages = {S94-8}, pmid = {21258597}, issn = {1598-6357}, mesh = {Asbestos/toxicity ; Carcinogens/toxicity ; Chromium/toxicity ; Female ; Humans ; Lung Neoplasms/chemically induced/*epidemiology/*etiology ; Male ; Mesothelioma/epidemiology/*etiology ; Occupational Diseases/chemically induced/*epidemiology/etiology ; Occupational Exposure/*adverse effects ; Pneumoconiosis/complications ; Republic of Korea/epidemiology ; Silicon Dioxide/toxicity ; Workers' Compensation ; }, abstract = {Malignant mesothelioma and lung cancer are representative examples of occupational cancer. Lung cancer is the leading cause of cancer death, and the incidence of malignant mesothelioma is expected to increase sharply in the near future. Although information about lung carcinogen exposure is limited, it is estimated that the number of workers exposed to carcinogens has declined. The first official case of occupational cancer was malignant mesothelioma caused by asbestos exposure in the asbestos textile industry in 1992. Since then, compensation for occupational respiratory cancer has increased. The majority of compensated lung cancer was due to underlying pneumoconiosis. Other main causative agents of occupational lung cancer included asbestos, hexavalent chromium, and crystalline silica. Related jobs included welders, foundry workers, platers, plumbers, and vehicle maintenance workers. Compensated malignant mesotheliomas were associated with asbestos exposure. Epidemiologic studies conducted in Korea have indicated an elevated risk of lung cancer in pneumoconiosis patients, foundry workers, and asbestos textile workers. Occupational respiratory cancer has increased during the last 10 to 20 yr though carcinogen-exposed population has declined in the same period. More efforts to advance the systems for the investigation, prevention and management of occupational respiratory cancer are needed.}, } @article {pmid21257924, year = {2011}, author = {Aldieri, E and Riganti, C and Silvagno, F and Orecchia, S and Betta, PG and Doublier, S and Gazzano, E and Polimeni, M and Bosia, A and Ghigo, D}, title = {Antioxidants prevent the RhoA inhibition evoked by crocidolite asbestos in human mesothelial and mesothelioma cells.}, journal = {American journal of respiratory cell and molecular biology}, volume = {45}, number = {3}, pages = {625-631}, doi = {10.1165/rcmb.2010-0089OC}, pmid = {21257924}, issn = {1535-4989}, mesh = {Antioxidants/metabolism ; Asbestos ; Asbestos, Crocidolite/*chemistry ; Cell Line ; Epithelium/*pathology ; Guanosine Triphosphate/chemistry ; Humans ; L-Lactate Dehydrogenase/metabolism ; Lipid Peroxidation ; Mesothelioma/*metabolism ; Microscopy, Fluorescence/methods ; NF-kappa B/metabolism ; Oxidative Stress ; Reactive Oxygen Species ; Signal Transduction ; rhoA GTP-Binding Protein/*metabolism ; }, abstract = {Asbestos is a naturally occurring fibrous silicate, whose inhalation is highly related to the risk of developing malignant mesothelioma (MM), and crocidolite is one of its most oncogenic types. The mechanism by which asbestos may cause MM is unclear. We have previously observed that crocidolite in human MM (HMM) cells induces NF-κB activation and stimulates the synthesis of nitric oxide by inhibiting the RhoA signaling pathway. In primary human mesothelial cells (HMCs) and HMM cells exposed to crocidolite asbestos, coincubated or not with antioxidants, we evaluated cytotoxicity and oxidative stress induction (lipid peroxidation) and the effect of asbestos on the RhoA signaling pathway (RhoA GTP binding, Rho kinase activity, RhoA prenylation, hydroxy-3-methylglutharyl-CoA reductase activity). In this paper we show that the reactive oxygen species generated by the incubation of crocidolite with primary HMCs and three HMM cell lines mediate the inhibition of 3-hydroxy-3-methylglutharyl-CoA reductase (HMGCR). The coincubation of HMCs and HMM cells with crocidolite together with antioxidants, such as Tempol, Mn-porphyrin, and the association of superoxide dismutase and catalase, prevented the cytotoxicity and lipoperoxidation caused by crocidolite alone as well as the decrease of HMGCR activity and restored the RhoA/RhoA-dependent kinase activity and the RhoA prenylation. The same effect was observed when the oxidizing agent menadione was administrated to the cells in place of crocidolite. Such a mechanism could at least partly explain the effects exerted by crocidolite fibers in mesothelial cells.}, } @article {pmid21245096, year = {2011}, author = {Murakami, H and Mizuno, T and Taniguchi, T and Fujii, M and Ishiguro, F and Fukui, T and Akatsuka, S and Horio, Y and Hida, T and Kondo, Y and Toyokuni, S and Osada, H and Sekido, Y}, title = {LATS2 is a tumor suppressor gene of malignant mesothelioma.}, journal = {Cancer research}, volume = {71}, number = {3}, pages = {873-883}, doi = {10.1158/0008-5472.CAN-10-2164}, pmid = {21245096}, issn = {1538-7445}, mesh = {Cell Cycle Proteins/genetics ; Cell Growth Processes/genetics ; Cell Line, Tumor ; Chromosomes, Human, Pair 13 ; Comparative Genomic Hybridization ; *Gene Deletion ; Gene Expression Regulation, Neoplastic ; Gene Silencing ; *Genes, Tumor Suppressor ; Humans ; Immunohistochemistry ; Mesothelioma/*genetics/pathology ; Neurofibromin 2/genetics ; Protein Serine-Threonine Kinases/*genetics ; Transduction, Genetic ; Tumor Suppressor Proteins/*genetics ; }, abstract = {Malignant mesothelioma (MM) is an aggressive neoplasm associated with asbestos exposure. We carried out genome-wide array-based comparative genomic hybridization analysis with 14 MM cell lines. Three cell lines showed overlapping homozygous deletion at chromosome 13q12, which harbored the LATS2 (large tumor suppressor homolog 2) gene. With 6 other MM cell lines and 25 MM tumors, we found 10 inactivating homozygous deletions or mutations of LATS2 among 45 MMs. LATS2 encodes a serine/threonine kinase, a component of the Hippo tumor-suppressive signaling pathway, and we transduced LATS2 in MM cells with its mutation. Transduction of LATS2 inactivated oncoprotein YAP, a transcriptional coactivator, via phosphorylation, and inhibited MM cell growth. We also analyzed LATS2 immunohistochemically and found that 13 of 45 MM tumors had low expression of LATS2. Because NF2 is genetically mutated in 40% to 50% of MM, our data indicate that Hippo pathway dysregulation is frequent in MM cells with inactivation of LATS2 or an upstream regulator of this pathway, Merlin, which is encoded by NF2. Thus, our results suggest that the inactivation of LATS2 is one of the key mechanisms for constitutive activation of YAP, which induces deregulation of MM cell proliferation.}, } @article {pmid21238604, year = {2011}, author = {Marini, V and Michelazzi, L and Cioé, A and Fucile, C and Spigno, F and Robbiano, L}, title = {Exposure to asbestos: correlation between blood levels of mesothelin and frequency of micronuclei in peripheral blood lymphocytes.}, journal = {Mutation research}, volume = {721}, number = {1}, pages = {114-117}, doi = {10.1016/j.mrgentox.2010.12.014}, pmid = {21238604}, issn = {0027-5107}, mesh = {Asbestos/*toxicity ; Environmental Exposure ; GPI-Linked Proteins/blood ; Humans ; Lymphocytes/ultrastructure ; Membrane Glycoproteins/*blood ; Mesothelin ; Micronuclei, Chromosome-Defective/*chemically induced ; Middle Aged ; }, abstract = {Inhalation of asbestos, a mineral extensively used in a variety of applications, is strongly associated with malignant mesothelioma (MM), a fatal cancer of the pleura. Soluble mesothelin-related peptides (SMRP) are a promising biomarker suggested for the screening of MM in healthy asbestos-exposed subjects. In the present study a comparison of micronucleus (Mn) frequencies in peripheral blood lymphocytes (PBL) between 44 asbestos-exposed and 22 control individuals has been performed, and the correlation with serum SMRP has been examined. SMRP levels were found to be significantly higher in subjects exposed to asbestos and in their various subgroups than in controls. Concerning micronucleated lymphocytes, a statistically significant difference from controls was seen in the percentages of both micronucleated mononucleated lymphocytes (MnMNL) and micronucleated binucleated lymphocytes (MnBNL), but the difference was markedly higher for the percentage of micronucleated polynucleated lymphocytes (MnPNL). With respect to the correlation between the frequency of the three types of micronucleated lymphocytes and serum-SMRP values of asbestos-exposed subjects, it was statistically significant for MnMNL, but not for MnBNL and MnPNL.}, } @article {pmid21233673, year = {2011}, author = {Kao, SC and Lee, K and Armstrong, NJ and Clarke, S and Vardy, J and van Zandwijk, N and Reid, G and Burn, J and McCaughan, BC and Henderson, DW and Klebe, S}, title = {Validation of tissue microarray technology in malignant pleural mesothelioma.}, journal = {Pathology}, volume = {43}, number = {2}, pages = {128-132}, doi = {10.1097/PAT.0b013e328342016c}, pmid = {21233673}, issn = {1465-3931}, mesh = {Antibodies, Monoclonal/metabolism ; Antibodies, Monoclonal, Murine-Derived ; Biomarkers, Tumor/metabolism ; Calbindin 2 ; Humans ; Mesothelioma/*diagnosis/metabolism ; Pleural Neoplasms/*diagnosis/metabolism ; Reproducibility of Results ; S100 Calcium Binding Protein G/metabolism ; Tissue Array Analysis/*methods ; }, abstract = {AIMS: Tissue microarray (TMA) technology has been utilised for assessment of cancers including malignant pleural mesothelioma (MPM). Given the intralesional heterogeneity of MPM, it is questionable if TMAs can adequately represent MPMs. We here investigate the validity of TMAs for MPM.

METHODS: TMAs were constructed from at least five cores for each of 80 archival tumours processed by two centres between 1994 and 2009. The percentage of cases correctly subtyped on TMAs compared with whole sections, in relation to the number of cores analysed, was calculated. Immunohistochemical labelling for calretinin and D2-40 was performed on TMAs and whole sections. To evaluate the validity of quantitative immunohistochemistry, percentages of positive cells were recorded and two-way analysis of variance (ANOVA) performed.

RESULTS: Five cores were assessable for 91% of patients. Four cores were sufficient to reach concordance with the whole-section result in 98% of cases for calretinin and 99% for D2-40. The correlation of the quantitative scores between the whole section and TMA cores was statistically significant (D2-40, rho = 0.84, p < 2.2e-16; calretinin, rho = 0.65, p = 7.9e-11). Neither the origin nor age of the blocks affected the results.

CONCLUSION: If a minimum of four cores is used, TMA is an appropriate method for immunohistochemistry in MPM.}, } @article {pmid21227534, year = {2011}, author = {Zhong, J and Lardinois, D and Szilard, J and Tamm, M and Roth, M}, title = {Rat mesothelioma cell proliferation requires p38δ mitogen activated protein kinase and C/EBP-α.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {73}, number = {2}, pages = {166-170}, doi = {10.1016/j.lungcan.2010.12.003}, pmid = {21227534}, issn = {1872-8332}, mesh = {Animals ; Becaplermin ; CCAAT-Enhancer-Binding Protein-alpha/genetics/*metabolism ; Cell Line, Tumor ; Cell Nucleus/metabolism ; *Cell Proliferation ; Gene Expression ; Mesothelioma/*metabolism ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3/metabolism ; Mitogens/pharmacology ; Phosphorylation ; Platelet-Derived Growth Factor/pharmacology ; Pleural Neoplasms/*metabolism ; Protein Isoforms/metabolism ; Proto-Oncogene Proteins c-sis ; Rats ; Rats, Inbred F344 ; p38 Mitogen-Activated Protein Kinases/genetics/*metabolism ; }, abstract = {Pleural malignant mesothelioma is a rare but deadly tumour mainly induced by asbestos inhalation. Despite the ban of asbestos in 1990 in 52 countries, mesothelioma cases still increase worldwide. In pleural mesothelioma, p38 mitogen activated protein kinases (MAPK) have been suggested to play a major role in carcinogenesis and aggressiveness of tumours. The aim of this study was to determine the role of the different four p38 MAPK isoforms and their effect on proliferation together with the underlying signalling pathways in a rat pleural mesothelioma cell line. Rat pleural mesothelioma cells were stimulated with platelet-derived growth factor (PDGF)-BB and/or transforming growth factor beta (TGF)-β. MAPK and transcription factor expression and activation was monitored in the cytosol and nucleus by immuno-blotting. Proliferation was determined by manual cell count and siRNAs were used to control MAPK and transcription factor expression and action. Only PDGF-BB, but not TGF-β1 induced proliferation via activated Erk1/2 and p38 MAPK. The p38α and δ isoforms were expressed in the cytosol, and upon activation p38δ translocated into the nucleus, while p38α remained in the cytosol. No other p38 isoform was expressed by rat mesothelioma cells. C/EBP-α was found in both the cytosol and the nucleus, while C/EBP-β was not expressed at all. PDGF-BB induced proliferation was suppressed by down-regulation of either Erk1/2, or p38δ MAPK, or C/EBP-α. Furthermore, TGF-β inhibited PDGF-BB induced proliferation by interruption of p38 MAPK signalling. From this rat model, we conclude that in pleural mesothelioma, p38δ in C/EBP-α mediate proliferation and thus may represent new targets in mesothelioma therapy.}, } @article {pmid21226381, year = {2010}, author = {Sartorio, E}, title = {[Mondovi: who monitors the former exposed to asbestos?].}, journal = {Epidemiologia e prevenzione}, volume = {34}, number = {1-2}, pages = {61-62}, pmid = {21226381}, issn = {1120-9763}, mesh = {Asbestos/*adverse effects ; Asbestosis/diagnosis/*mortality/prevention & control ; *Community Networks/organization & administration ; Environmental Pollution/legislation & jurisprudence/*prevention & control ; Humans ; Italy/epidemiology ; Mesothelioma/diagnosis/*mortality/prevention & control ; Pleural Neoplasms/diagnosis/*mortality/prevention & control ; Population Surveillance ; Public Health ; }, } @article {pmid21194504, year = {2010}, author = {Méndez-Vargas, MM and López-Rojas, P and Campos-Pujal, GA and Marín-Cotoñieto, IA and Salinas-Tovar, S and Fernández-Muñoz, Mde J}, title = {Pleural mesothelioma in paraoccupational, environmental and occupational patients exposed to asbestos.}, journal = {Revista medica del Instituto Mexicano del Seguro Social}, volume = {48}, number = {4}, pages = {361-366}, pmid = {21194504}, issn = {0443-5117}, mesh = {Asbestos/*adverse effects ; Cross-Sectional Studies ; Environmental Exposure/*adverse effects ; Female ; Humans ; Male ; Mesothelioma/*etiology ; Middle Aged ; Occupational Diseases/*etiology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*etiology ; Retrospective Studies ; }, abstract = {OBJECTIVE: To identify the characteristics of pleural mesothelioma in patients exposed to asbestos.

METHODS: A transverse study in 3700 cases of lung cancer was conducted. There were identified 21 cases with mesothelioma. Age, gender, smoking history, cancer development, dissemination, cytohistochemistry, lethality and total lung capacity were studied. ANOVA test was used.

RESULTS: The incidence was of 0.45/100,000 patients. Four (19%) corresponded to occupational exposure (OE), seven (33%) para-occupational (PE) and ten (48%) environmental (EE). The mean age at detection was 50 years for PE, 55 years for EE and 64 years for OE. Twenty cases were male. Thirteen patients (62%) were active cigarette smokers. The latency time in PE mesothelioma was 34.5 years, in OE 40 years, and in EE more than 40 years. In 19 (90%) cases the tumor was disseminated. Diagnosis was confirmed by cytohistochemistry. Malignant mesothelioma was reported in 19 (90%) cases. The survival period was 5 months for OE patients, 10 in PE and 16 in EE.

CONCLUSIONS: There is a low incidence of malignant mesothelioma in our population. Male was the predominant group. Occupational and paraoccupational exposure predominated in patients.}, } @article {pmid21193386, year = {2011}, author = {Baumann, F and Maurizot, P and Mangeas, M and Ambrosi, JP and Douwes, J and Robineau, B}, title = {Pleural mesothelioma in New Caledonia: associations with environmental risk factors.}, journal = {Environmental health perspectives}, volume = {119}, number = {5}, pages = {695-700}, pmid = {21193386}, issn = {1552-9924}, mesh = {Asbestos, Serpentine/*toxicity ; Confidence Intervals ; Environmental Exposure/*adverse effects ; Humans ; Mesothelioma/*chemically induced/*epidemiology ; New Caledonia ; Odds Ratio ; Pleural Neoplasms/*chemically induced/*epidemiology ; Risk Factors ; }, abstract = {BACKGROUND: High incidences of malignant mesothelioma (MM) have been observed in New Caledonia. Previous work has shown an association between MM and soil containing serpentinite.

OBJECTIVES: We studied the spatial and temporal variation of MM and its association with environmental factors.

METHODS: We investigated the 109 MM cases recorded in the Cancer Registry of New Caledonia between 1984 and 2008 and performed spatial, temporal, and space-time cluster analyses. We conducted an ecological analysis involving 100 tribes over a large area including those with the highest incidence rates. Associations with environmental factors were assessed using logistic and Poisson regression analyses.

RESULTS: The highest incidence was observed in the Houaïlou area with a world age-standardized rate of 128.7 per 100,000 person-years [95% confidence interval (CI), 70.41-137.84]. A significant spatial cluster grouped 18 tribes (31 observed cases vs. 8 expected cases; p = 0.001), but no significant temporal clusters were identified. The ecological analyses identified serpentinite on roads as the greatest environmental risk factor (odds ratio = 495.0; 95% CI, 46.2-4679.7; multivariate incidence rate ratio = 13.0; 95% CI, 10.2-16.6). The risk increased with serpentinite surface, proximity to serpentinite quarries and distance to the peridotite massif. The association with serpentines was stronger than with amphiboles. Living on a slope and close to dense vegetation appeared protective. The use of whitewash, previously suggested to be a risk factor, was not associated with MM incidence.

CONCLUSIONS: Presence of serpentinite on roads is a major environmental risk factor for mesothelioma in New Caledonia.}, } @article {pmid22432060, year = {2012}, author = {Nasreen, N and Khodayari, N and Mohammed, KA}, title = {Advances in malignant pleural mesothelioma therapy: targeting EphA2 a novel approach.}, journal = {American journal of cancer research}, volume = {2}, number = {2}, pages = {222-234}, pmid = {22432060}, issn = {2156-6976}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive neoplasm with a poor prognosis. MPM grows from the mesothelial cells lining the surface of the lung and chest wall called Pleura. Exposure to asbestos is mainly linked to the development of MPM. Approximately 80% of the tumors are pleural in origin, and up to 3000 people are diagnosed with MPM in the United States annually. The incidence of MPM is expected to rise in the coming decades particularly in the developing countries. Although there is an increase in the awareness of danger associated with the use of asbestos, its use is still prevalent in Australia and Asia because of its durability and low cost. This further warns and adds to the mortality and morbidity of patients with MPM globally. The traditional treatment strategies have shown only modest improvement towards the disease. MPM is difficult to treat because of the fact that the time between the exposure to asbestos and the appearance of symptoms is extremely delayed, and also due to tumor involvement with the pleural surface and the adjoining tissues such as the chest wall, pericardium and sub-diaphragmatic organs. Despite advances in the diagnostic and treatment approaches the median survival rate for MPM is between 9 to 17 months. The standard care with double agent has shown modest improvement however, multimodality approach using novel targets may have potential to achieve the improvement in the survival rate. In this review we give an update on the conventional treatment modalities and discuss about various molecular targets including receptor EphA2, a novel target gene which may be considered as a biomarker for the diagnosis and treatment of MPM.}, } @article {pmid21182425, year = {2011}, author = {Donaldson, K and Murphy, F and Schinwald, A and Duffin, R and Poland, CA}, title = {Identifying the pulmonary hazard of high aspect ratio nanoparticles to enable their safety-by-design.}, journal = {Nanomedicine (London, England)}, volume = {6}, number = {1}, pages = {143-156}, doi = {10.2217/nnm.10.139}, pmid = {21182425}, issn = {1748-6963}, support = {//Department of Health/United Kingdom ; }, mesh = {Animals ; Asbestos/*adverse effects ; Humans ; Lung Diseases/*etiology ; Mesothelioma/etiology ; Mineral Fibers/*adverse effects ; Nanoparticles/*adverse effects/chemistry/ultrastructure ; }, abstract = {High aspect ratio, or fiber-shaped, nanoparticles (HARNs) represent a growth area in nanotechnology as their useful properties become more apparent. Carbon nanotubes, the best known and studied of the HARNs are handled on an increasingly large scale, with subsequent potential for human inhalation exposure. Their resemblance to asbestos fibers precipitated fears that they might show the same type of pathology as that caused by asbestos and there is emerging evidence to support this possibility. The large number of other HARNs, including nanorods, nanowires and other nanofibers, require similar toxicological scrutiny. In this article we describe the unusual hazard associated with fibers, with special reference to asbestos, and address the features of fibers that dictate their pathogenicity as developed in the fiber pathogenicity paradigm. This paradigm is a robust structure:toxicity model that identifies thin, long, biopersistent fibers as the effective dose for fiber-type pathogenic effects. It is likely that HARNs will in general conform to the paradigm and such an understanding of the features that make fibers pathogenic should enable us to design safer HARNs.}, } @article {pmid21177406, year = {2011}, author = {Creaney, J and Francis, RJ and Dick, IM and Musk, AW and Robinson, BW and Byrne, MJ and Nowak, AK}, title = {Serum soluble mesothelin concentrations in malignant pleural mesothelioma: relationship to tumor volume, clinical stage and changes in tumor burden.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {17}, number = {5}, pages = {1181-1189}, doi = {10.1158/1078-0432.CCR-10-1929}, pmid = {21177406}, issn = {1557-3265}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/blood ; Female ; GPI-Linked Proteins/*blood ; Humans ; Male ; Mesothelin ; Mesothelioma/*blood/drug therapy/pathology ; Middle Aged ; Neoplasm Staging ; Pleural Neoplasms/*blood/drug therapy/pathology ; Positron-Emission Tomography ; Prognosis ; Prospective Studies ; Tomography, X-Ray Computed ; Tumor Burden ; }, abstract = {PURPOSE: To examine the clinical utility of soluble mesothelin in patients with malignant pleural mesothelioma.

EXPERIMENTAL DESIGN: A total of 97 patients (female: 11; male: 86) were prospectively enrolled, longitudinal serum samples collected, and mesothelin concentrations determined. Baseline mesothelin levels were analyzed relative to tumor stage, presence of metastatic disease, the positron emission tomography (PET) parameters maximum standardized uptake value, tumor volume, total glycolytic volume, and survival. Changes in mesothelin level were correlated to objective response to chemotherapy, as assessed radiologically and by PET imaging, and with patient survival.

RESULTS: Baseline mesothelin levels greater than 5 nmol/L were a significant negative prognostic indicator (HR = 2.25; 95% CI, 1.20-4.21) and correlated with tumor stage and volume. In 55 patients who received chemotherapy, change in mesothelin correlated with radiological response (χ(2) = 11.32; P = 0.023) and change in metabolically active tumor volume (r = 0.58; P < 0.01). Median survival for patients with a reduction in mesothelin following chemotherapy (19 months) was significantly longer than for patients with increased mesothelin (5 months; P < 0.001).

CONCLUSION: These findings show the potential value of changes in mesothelin levels for prognostication and monitoring of treatment response in mesothelioma.}, } @article {pmid21173562, year = {2010}, author = {Shin, SM and Park, SM and Hwang, BS and Seol, SH and Seo, HE and Kim, SH and Gu, MJ and Shin, JY}, title = {[A case of peritoneal mesothelioma with direct invasion to gastric mucosa].}, journal = {The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi}, volume = {56}, number = {6}, pages = {377-381}, doi = {10.4166/kjg.2010.56.6.377}, pmid = {21173562}, issn = {1598-9992}, mesh = {Gastric Mucosa/*pathology ; Humans ; Male ; Mesothelioma/*diagnosis/pathology ; Middle Aged ; Neoplasm Invasiveness ; Peritoneal Neoplasms/*diagnosis/pathology ; Stomach Neoplasms/*pathology/secondary ; Tomography, X-Ray Computed ; }, abstract = {Mesothelioma is a rare aggressive tumor arising from the mesothelial cell and regarded as universally fatal disease with average survival around 1 year. The incidence rate is varied from one to forty per million in different countries and increasing by the year. The most common site of tumor origin is the pleura and only 20% to 33% of mesothelioma arise from the peritoneum. There are increasing reports of malignant mesothelioma with forty to fifty fatal cases per year in Korea. Histological studies with immunohistochemical stain is helpful for the diagnosis of peritoneal mesothelioma and imaging modality alone is not sufficient for diagnosis, so it is difficult to confirm diagnosis. A 64-year-old male patient was admitted to the hospital with a palpable mass on abdomen. The 6x6 cm sized huge mass was seen on the body of stomach adjacent to the peritoneum. We report a case of malignant peritoneal mesothelioma without evident exposure to asbestos, of which direct invasion to the gastric mucosa was confirmed by endoscopic biopsy and immunohistochemical stain.}, } @article {pmid21173534, year = {2011}, author = {Haber, SE and Haber, JM}, title = {Malignant mesothelioma: a clinical study of 238 cases.}, journal = {Industrial health}, volume = {49}, number = {2}, pages = {166-172}, doi = {10.2486/indhealth.ms1147}, pmid = {21173534}, issn = {1880-8026}, mesh = {Adult ; Aged ; Aged, 80 and over ; Environmental Exposure/adverse effects ; Female ; Humans ; Male ; Mesothelioma/diagnosis/*epidemiology ; Middle Aged ; Occupational Diseases/*epidemiology ; Occupational Exposure/*adverse effects ; Peritoneal Neoplasms/diagnosis/*epidemiology ; Respiratory Tract Neoplasms/diagnosis/*epidemiology ; Sex Distribution ; Smoking/epidemiology ; Time Factors ; United States/epidemiology ; }, abstract = {Malignant mesothelioma is a diffuse tumor arising in the pleura, peritoneum, or other serosal surface and is closely associated with asbestos exposure. An estimated 2,500 to 3,000 cases are diagnosed each year in the United States. Although there are individual case reports and small series detailing the clinical aspects of mesothelioma, few studies examine a large series of patients with malignant mesothelioma from the clinical perspective. This study reports on the findings of 238 cases of malignant mesothelioma from a private consultative medical practice. Most cases had a history of occupational asbestos exposure. The mean latency was 48.5 yr, with women having a longer latency than men. The mean age at diagnosis was 70. Survival overall was poor (mean 8.8 months), but treatment was beneficial (mean 11.3 versus 6.4 months). Epithelioid histology conferred a survival advantage over sarcomatoid and responded better to treatment. Our data support an inverse relationship between asbestos dose and latency.}, } @article {pmid21171229, year = {2010}, author = {Kirby, T}, title = {Canada accused of hypocrisy over asbestos exports.}, journal = {Lancet (London, England)}, volume = {376}, number = {9757}, pages = {1973-1974}, doi = {10.1016/s0140-6736(10)62242-8}, pmid = {21171229}, issn = {1474-547X}, mesh = {Asbestos/*adverse effects ; Asbestos, Serpentine/adverse effects ; Canada/epidemiology ; *Carcinogens ; *Commerce/economics/ethics/trends ; Construction Materials/adverse effects ; Developed Countries ; Developing Countries ; Environmental Exposure/*adverse effects ; Global Health ; Humans ; International Cooperation ; Lung Diseases/chemically induced/epidemiology ; Lung Neoplasms/*chemically induced/*epidemiology ; Mesothelioma/*chemically induced/*epidemiology ; Mining/economics/standards ; Occupational Exposure/adverse effects ; Public Health ; Public Policy ; Quebec ; }, } @article {pmid21164435, year = {2010}, author = {}, title = {Asbestos scandal.}, journal = {Nature}, volume = {468}, number = {7326}, pages = {868}, doi = {10.1038/468868a}, pmid = {21164435}, issn = {1476-4687}, mesh = {Asbestos/*adverse effects/economics/*supply & distribution ; Asbestos, Serpentine/adverse effects/supply & distribution ; Carcinogens/supply & distribution/toxicity ; Construction Materials/adverse effects/economics/supply & distribution ; Humans ; Industry/economics/*legislation & jurisprudence ; Internationality ; Mesothelioma/*chemically induced/epidemiology/prevention & control ; }, } @article {pmid21163253, year = {2011}, author = {Ghani, FI and Yamazaki, H and Iwata, S and Okamoto, T and Aoe, K and Okabe, K and Mimura, Y and Fujimoto, N and Kishimoto, T and Yamada, T and Xu, CW and Morimoto, C}, title = {Identification of cancer stem cell markers in human malignant mesothelioma cells.}, journal = {Biochemical and biophysical research communications}, volume = {404}, number = {2}, pages = {735-742}, doi = {10.1016/j.bbrc.2010.12.054}, pmid = {21163253}, issn = {1090-2104}, mesh = {Animals ; Antigens, CD/*metabolism ; Biomarkers, Tumor/*metabolism ; CD24 Antigen/*metabolism ; Cell Line, Tumor ; Dipeptidyl Peptidase 4/*metabolism ; Humans ; Membrane Glycoproteins/*metabolism ; Mesothelioma/*metabolism/pathology ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Neoplastic Stem Cells/*metabolism/pathology ; Tetraspanin 29 ; }, abstract = {Malignant mesothelioma (MM) is an aggressive and therapy-resistant neoplasm arising from the pleural mesothelial cells and usually associated with long-term asbestos exposure. Recent studies suggest that tumors contain cancer stem cells (CSCs) and their stem cell characteristics are thought to confer therapy-resistance. However, whether MM cell has any stem cell characteristics is not known. To understand the molecular basis of MM, we first performed serial transplantation of surgical samples into NOD/SCID mice and established new cell lines. Next, we performed marker analysis of the MM cell lines and found that many of them contain SP cells and expressed several putative CSC markers such as CD9, CD24, and CD26. Interestingly, expression of CD26 closely correlated with that of CD24 in some cases. Sorting and culture assay revealed that SP and CD24(+) cells proliferated by asymmetric cell division-like manner. In addition, CD9(+) and CD24(+) cells have higher potential to generate spheroid colony than negative cells in the stem cell medium. Moreover, these marker-positive cells have clear tendency to generate larger tumors in mouse transplantation assay. Taken together, our data suggest that SP, CD9, CD24, and CD26 are CSC markers of MM and could be used as novel therapeutic targets.}, } @article {pmid21162719, year = {2010}, author = {Bitchatchi, E and Kayser, K and Perelman, M and Richter, ED}, title = {Mesothelioma and asbestosis in a young woman following occupational asbestos exposure: Short latency and long survival: Case Report.}, journal = {Diagnostic pathology}, volume = {5}, number = {}, pages = {81}, pmid = {21162719}, issn = {1746-1596}, mesh = {Adult ; Antineoplastic Agents/administration & dosage ; Asbestos/*adverse effects ; Asbestosis/diagnosis/*etiology/therapy ; Biopsy ; Chemotherapy, Adjuvant ; Cisplatin/administration & dosage ; Construction Materials/*adverse effects ; Female ; Humans ; Infusions, Parenteral ; Mesothelioma/*chemically induced/diagnosis/therapy ; Occupational Exposure ; Pleural Neoplasms/*chemically induced/diagnosis/therapy ; Pneumonectomy ; Time Factors ; Treatment Outcome ; }, abstract = {A 27-year-old female white-collar worker was diagnosed in 1998 with mesothelioma eight and one-half years following first exposure as a bystander to debris in a site in which asbestos-containing building materials were being dismantled and rebuilding work took place. Prodromal back pain had been present for a year and a half. She underwent extrapleural pneumectomy and received an intrapleural infusion of cisplatin post-operatively. Exposure to asbestos was verified by contemporary reports and lung biopsy, which demonstrated asbestos bodies and microscopic interstitial fibrosis -conforming evidence for asbestosis. The patient is alive and well 12 years after diagnosis and 14 years after onset of symptoms. The combination of an extremely short latency period and long survival following occupational exposure to asbestos dust is unique.}, } @article {pmid21160794, year = {2009}, author = {Munkholm-Larsen, S and Cao, CQ and Yan, TD}, title = {Malignant peritoneal mesothelioma.}, journal = {World journal of gastrointestinal surgery}, volume = {1}, number = {1}, pages = {38-48}, pmid = {21160794}, issn = {1948-9366}, abstract = {Malignant mesothelioma is a highly aggressive neoplasm. The incidence of malignant mesothelioma is increasing worldwide. Diffuse malignant peritoneal mesothelioma (DMPM) represents one-fourth of all mesotheliomas. Association of asbestos exposure with DMPM has been observed, especially in males. The great majority of patients present with abdominal pain and distension, caused by accumulation of tumors and ascitic fluid. In the past, DMPM was considered a pre-terminal condition; therefore attracted little attention. Patients invariably died from their disease within a year. Recently, several prospective trials have demonstrated a median survival of 40 to 90 mo and 5-year survival of 30% to 60% after combined treatment using cytoreductive surgery and perioperative intraperitoneal chemotherapy. This remarkable improvement in survival has prompted new search into the medical science related to DMPM, a disease previously ignored as uninteresting. This review article focuses on the key advances in the epidemiology, diagnosis, staging, treatments and prognosis of DMPM that have occurred in the past decade.}, } @article {pmid21158701, year = {2011}, author = {Rai, AJ and Flores, RM}, title = {Association of malignant mesothelioma and asbestos related conditions with ovarian cancer: shared biomarkers and a possible etiological link?.}, journal = {Clinical chemistry and laboratory medicine}, volume = {49}, number = {1}, pages = {5-7}, doi = {10.1515/CCLM.2011.027}, pmid = {21158701}, issn = {1437-4331}, mesh = {Asbestos/*poisoning ; Biomarkers, Tumor/*metabolism ; Female ; Humans ; Lung Neoplasms/*etiology/metabolism/pathology ; Mesothelioma/*etiology/metabolism/pathology ; Ovarian Neoplasms/chemistry/*etiology/metabolism ; }, } @article {pmid21156353, year = {2011}, author = {Mensi, C and Giacomini, S and Sieno, C and Consonni, D and Riboldi, L}, title = {Pericardial mesothelioma and asbestos exposure.}, journal = {International journal of hygiene and environmental health}, volume = {214}, number = {3}, pages = {276-279}, doi = {10.1016/j.ijheh.2010.11.005}, pmid = {21156353}, issn = {1618-131X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Female ; Heart Neoplasms/epidemiology/*etiology ; Humans ; Incidence ; Inhalation Exposure ; Italy ; Male ; Mesothelioma/epidemiology/*etiology ; Middle Aged ; Occupational Diseases/epidemiology/*etiology ; Occupational Exposure/*adverse effects ; Pericardium/*pathology ; Pleural Neoplasms/epidemiology/*etiology ; Young Adult ; }, abstract = {Pericardial mesothelioma (PM) accounts for 0.7% of all malignant mesotheliomas. Although asbestos exposure is a recognized etiological factor for pleural and peritoneal mesotheliomas, its role in the development of PM is controversial. The aim of this study is to describe the characteristics of PM cases occurred in Lombardy, a highly industrialized Region of Northern Italy. From the Lombardy Mesothelioma Registry we selected the incident cases of PM registered in the Lombardy Region between 2000 and 2009 and we abstracted clinical characteristics and history of asbestos exposure. We identified 8 cases (6 men and 2 women), with a median age at diagnosis of 55.5 years, representing 0.3% of all mesothelioma cases (n = 3059). The age-standardized incidence rate was 0.09 per million/year. Occupational exposure to asbestos was documented in 5 of the 7 cases for which we obtained an interview. Our findings support the role of asbestos in the pathogenesis of PM.}, } @article {pmid21148743, year = {2011}, author = {Maeda, M and Nishimura, Y and Hayashi, H and Kumagai, N and Chen, Y and Murakami, S and Miura, Y and Hiratsuka, J and Kishimoto, T and Otsuki, T}, title = {Reduction of CXC chemokine receptor 3 in an in vitro model of continuous exposure to asbestos in a human T-cell line, MT-2.}, journal = {American journal of respiratory cell and molecular biology}, volume = {45}, number = {3}, pages = {470-479}, doi = {10.1165/rcmb.2010-0213OC}, pmid = {21148743}, issn = {1535-4989}, mesh = {Apoptosis ; Asbestos/*toxicity ; CD4-Positive T-Lymphocytes/cytology ; Cell Line ; Cluster Analysis ; Down-Regulation ; Enzyme-Linked Immunosorbent Assay/methods ; Humans ; Immune System ; In Vitro Techniques ; Interferon-gamma/metabolism ; Lung Neoplasms/metabolism ; Mesothelioma/metabolism ; Oligonucleotide Array Sequence Analysis ; Receptors, CXCR3/*biosynthesis ; T-Lymphocytes/*drug effects ; }, abstract = {Because patients with silicosis who are chronically exposed to silica particles develop not only pulmonary fibrosis, but also complications involving autoimmune diseases such as rheumatoid arthritis and systemic sclerosis, exposure to asbestos may affect the human immune system. This immunologic effect may impair antitumor immune function because cancer complications such as lung cancer and malignant mesothelioma are found in patients exposed to asbestos. To elucidate the antitumor immune status caused by CD4(+) T cells exposed to asbestos, an in vitro T-cell model of long-term and low-level exposure to chrysotile asbestos was established from a human adult T-cell leukemia virus-1-immortalized human polyclonal T cell line, MT-2, and the resulting six sublines showed resistance to asbestos-induced apoptosis after more than 8 months of continuous exposure. The results of DNA microarray analysis showed that the expression of 139 genes was altered by long-term and low-level exposure to asbestos, and the profile was almost similar among the six sublines when compared with the original MT-2 cells that had never been exposed to asbestos. Pathway and network analysis indicated a down-regulation of IFN-γ signaling and expression of CXC chemokine receptor 3 (CXCR3) in the sublines, whereas ELISA and flow cytometry analysis demonstrated a reduction in Th1-related IFN-γ production and cell-surface CXCR3 expression. These findings suggest that chronic exposure to asbestos may reduce antitumor immune status in CD4(+) T cells, and that an in vitro T-cell model may be useful in identifying molecules related to the impairment of antitumor immune function.}, } @article {pmid21141346, year = {2010}, author = {Mensi, C and Garberi, A and Bordini, L and Sieno, C and Riboldi, L}, title = {Asbestos-related diseases in entertainment workers.}, journal = {La Medicina del lavoro}, volume = {101}, number = {6}, pages = {416-418}, pmid = {21141346}, issn = {0025-7818}, mesh = {Aged ; Air Pollutants, Occupational/*adverse effects ; Asbestos/*adverse effects ; Asbestos, Crocidolite/adverse effects ; Asbestosis/etiology ; Calcinosis/etiology ; Female ; Humans ; Male ; Manufactured Materials/adverse effects ; Mesothelioma/*etiology ; Middle Aged ; Mineral Fibers/adverse effects ; Occupational Diseases/*etiology ; Pleural Diseases/etiology ; Pleural Neoplasms/*etiology ; Protective Clothing/adverse effects ; *Public Facilities/standards ; Time Factors ; }, abstract = {OBJECTIVES: To investigate asbestos exposure in 4 patients (3 cases of malignant mesothelioma and 1 case ofpleural plagues) previously employed in the entertainment business.

METHODS: The patients were seen at the Occupational Health Unit of the "Clinica del Lavoro Luigi Devoto" in Milan (Italy). Information regarding exposure to asbestos (occupational, environmental, and familial) was collected through a standardized questionnaire administered to the patients by an occupational physician.

RESULTS AND CONCLUSION: The presence of asbestos in the building structures and its use were described by all patients. The presence of asbestos in public buildings used for entertainment such as cinemas and theatres was in fact confirmed by the Occupational Health Services of the Local Heath Unit. An occupational aetiology was recognised in all the cases mentioned above, thus leading to the identification of an atypical occupational sector at risk in the past for asbestos exposure,}, } @article {pmid21141345, year = {2010}, author = {Riva, MA and Carnevale, F and Sironi, VA and De Vito, G and Cesana, G}, title = {Mesothelioma and asbestos, fifty years of evidence: Chris Wagner and the contribution of the Italian occupational medicine community.}, journal = {La Medicina del lavoro}, volume = {101}, number = {6}, pages = {409-415}, pmid = {21141345}, issn = {0025-7818}, mesh = {Asbestos/*adverse effects ; Congresses as Topic/history ; Disease Susceptibility ; Dissent and Disputes/history ; History, 20th Century ; Humans ; Italy ; Mesothelioma/epidemiology/etiology/*history ; Mineral Fibers/adverse effects ; Mining ; Occupational Diseases/epidemiology/etiology/*history ; *Occupational Medicine/organization & administration ; Pleural Neoplasms/epidemiology/etiology/*history ; South Africa ; Time Factors ; }, abstract = {BACKGROUND: One of the first studies that "convincingly" described the relationship between pleural mesothelioma and asbestos was made by Wagner, Sleggs and Marchard in 1960. This article, published fifty years ago, contains much of what we still know to-day about malignant mesothelioma.

OBJECTIVES: The aims of this article were to analyze the historical and scientific developments that led to the publication of Wagner's paper, to critically examine its contents and to consider the contribution to the initernational debate on the carcinogenesis of asbestos fibres made by occupational medicine in Italy in that period.

METHODS: A thorough analysis ofscientific and historical literature on the relationship between asbestos exposure and tumours was conducted, with special regard to the articles by Italian authors in the 1960's.

RESULTS: The decisive role of Wagner's paper in understanding the aetiopathogenetic mechanisms of asbestos-related tumours is inconfutable. In particular, his article clearly demonstrated the existence of a typical cancer of the mesothelium, expressing three fundamental principles of the epidemiology of occupational cancer: association with the carcinogen, latency and individual susceptibility. Enrico Vigliani, then director of the "Clinica del Lavoro" in Milan, made important contributions to this debate, also through the collection of data regarding mortality among Italian asbestos workers.

CONCLUSIONS: Wagner's 1960 paper can be considered as a milestone not only in the history of occupational and environmental health, but also in the evolution of other medical disciplines such as epidemiology, pathology and oncology. A re-appraisal of the Italian contributions to the international debate on this subject should be considered.}, } @article {pmid21141060, year = {2010}, author = {Haga, T and Nakajima, Y and Kitamura, A and Kuroda, F and Takiguchi, Y and Tatsumi, K}, title = {[Case of benign asbestos pleurisy with diffuse pleural thickening confirmed on autopsy].}, journal = {Nihon Kokyuki Gakkai zasshi = the journal of the Japanese Respiratory Society}, volume = {48}, number = {11}, pages = {821-824}, pmid = {21141060}, issn = {1343-3490}, mesh = {Aged ; Asbestosis/diagnosis/*pathology ; *Autopsy ; Fatal Outcome ; Humans ; Male ; Occupational Exposure ; Pleura/*pathology ; Pleural Diseases/diagnosis/*pathology ; Pleural Effusion/diagnosis/pathology ; Respiratory Insufficiency/etiology ; }, abstract = {We report a 65-year-old man with a 35-year history of occupational asbestos exposure. He presented at a nearby hospital with a complaint of dyspnea in 2002. Bilateral pleural effusion was revealed on a chest x-ray film. Chest CT revealed diffuse thickening of the pleura, bilateral pleural effusions and cardiac effusion, but no abnormal findings in the lung fields. Both pleural effusions were exudative, and lymphocytes were predominant. Antituberculous chemotherapy had no effect on the exudates. Thoracoscopic pleural biopsy was conducted to exclude malignant mesothelioma. No evidence of malignancy was found in pleural samples. The patient's condition was diagnosed as benign asbestos pleurisy with diffuse pleural thickening. He was referred to our hospital in June 2008. Bilateral pleural effusions continued to progress despite pleurodesis and frequent drainage of his pleural effusion. He suffered from respiratory failure and died in December 2008. We investigated the concentration of asbestos bodies in his lung tissue. There were 462 asbestos bodies per 1 g of dry lung tissue, which was relatively low considering the time of asbestos exposure. We report a rare case of benign asbestos pleurisy with diffuse pleural thickening confirmed by autopsy.}, } @article {pmid21132014, year = {2011}, author = {Ou, WB and Corson, JM and Flynn, DL and Lu, WP and Wise, SC and Bueno, R and Sugarbaker, DJ and Fletcher, JA}, title = {AXL regulates mesothelioma proliferation and invasiveness.}, journal = {Oncogene}, volume = {30}, number = {14}, pages = {1643-1652}, doi = {10.1038/onc.2010.555}, pmid = {21132014}, issn = {1476-5594}, mesh = {Alternative Splicing ; Antineoplastic Agents/pharmacology ; Cell Line, Tumor ; Cell Movement/drug effects/genetics ; Cell Proliferation/*drug effects ; Exons ; Gene Silencing ; Humans ; Intercellular Signaling Peptides and Proteins/isolation & purification ; Mesothelioma/drug therapy/*genetics/pathology ; Neoplasm Invasiveness/genetics ; Phosphorylation ; Pleural Neoplasms/drug therapy/*genetics/pathology ; Proto-Oncogene Proteins/antagonists & inhibitors/*genetics/metabolism ; Receptor Protein-Tyrosine Kinases/antagonists & inhibitors/*genetics/metabolism ; Sequence Deletion ; Signal Transduction/drug effects/genetics ; Axl Receptor Tyrosine Kinase ; }, abstract = {Mesothelioma is an asbestos-associated and notoriously chemotherapy-resistant neoplasm. Activation of the receptor tyrosine kinases (RTKs), epidermal growth factor receptor and MET, has been described in subsets of mesothelioma, suggesting that TKs might represent therapeutic targets in this highly lethal disease. We employed proteomic screening by phosphotyrosine immunoaffinity purification and tandem mass spectrometry to characterize RTK activation in mesothelioma cell lines. These assays demonstrated expression and activation of the AXL protein, which is an RTK with known oncogenic properties in non-mesothelial cancer types. AXL was expressed and activated strongly in 8 of 9 mesothelioma cell lines and 6 of 12 mesothelioma biopsies, including each of 12 mesotheliomas with spindle-cell histology. Somatic AXL mutations were not found, but all mesotheliomas expressed an alternatively spliced AXL transcript with in-frame deletion of exon 10, and six of seven mesothelioma cell lines expressed the AXL ligand, growth arrest-specific 6 (GAS6). GAS6 expression appeared to be functionally relevant, as indicated by modulation of AXL tyrosine phosphorylation by knockdown of endogeneous GAS6, and by administration of exogenous GAS6. AXL silencing by lentivirus-mediated short hairpin RNA suppressed mesothelioma migration and cellular proliferation due to G1 arrest. The AXL inhibitor DP-3975 inhibited cell migration and proliferation in mesotheliomas with strong AXL activation. DP-3975 response in these tumors was characterized by inhibition of PI3-K/AKT/mTOR and RAF/MAPK signaling. AXL inhibition suppressed mesothelioma anchorage-independent growth, with reduction in colony numbers and size. These studies suggest that AXL inhibitors warrant clinical evaluation in mesothelioma.}, } @article {pmid22427768, year = {2010}, author = {Akl, Y and Kaddah, S and Abdelhafeez, A and Salah, R and Lotayef, M}, title = {Epidemiology of mesothelioma in Egypt. A ten-year (1998-2007) multicentre study.}, journal = {Archives of medical science : AMS}, volume = {6}, number = {6}, pages = {926-931}, pmid = {22427768}, issn = {1896-9151}, abstract = {INTRODUCTION: Mesothelioma is a cancer strongly linked to exposure to carcinogenic minerals, especially asbestos. The aim of the study was to detect the incidence of malignant pleural mesothelioma (MPM) in Egypt, to clarify the impact of occupational and environmental risk factors, and to characterise its demographic features.

MATERIAL AND METHODS: They were 584 cases diagnosed as MPM detected in Cairo University Hospitals and National Cancer Institute from 1998 to 2007. Unfortunately, full epidemiological data were only available for 165 cases due to absence of a reliable registration system.

RESULTS: A steady increase in the number of cases was detected, from 24 in 1998, peaking at 82 cases in 2005, followed by a gradual decline (though still high) with 68 cases in 2006 and 51 cases in 2007. Male/female ratio was 1.35/1 (p > 0.05). The occupational exposure to asbestos was 13.9%. Residential exposure plays a major role in two regions, Helwan and Shoubra (27.3% and 20.6% respectively), while in Upper and Lower Egypt the level was 12.7% and 17.5% respectively. Kaplan-Meier survival for sex, residence and the pathological types epithelioid, biphasic and sarcomatoid was insignificant. The median survival for different grades and treatment modalities was significant (P < 0.001).

CONCLUSIONS: There was a steady increase in the incidence of MPM from 1998 to 2005 followed by a decline during 2006-2007. Mesothelioma in Egypt is mainly concentrated in areas of high environmental pollution. The decline within the last 2 years may be attributed to recent strict industrial preventive measures. However, a better environmental control programme would benefit Egypt.}, } @article {pmid21086578, year = {2010}, author = {Rezaei Kalantari, H}, title = {[Malignant peritoneal mesothelioma: a case report].}, journal = {Revue medicale de Liege}, volume = {65}, number = {9}, pages = {490-492}, pmid = {21086578}, issn = {0370-629X}, mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Fatal Outcome ; Humans ; Male ; Mesothelioma/*diagnosis/drug therapy ; Middle Aged ; Peritoneal Neoplasms/*diagnosis/drug therapy ; }, abstract = {I report two cases of malignant peritoneal mesothelioma. Mesothelioma is mostly a pleural disease whether visceral or parietal. Infra-diaphragmatic Mesothelioma accounts for only 10-20% of all mesotheliomas. In over 80% of the cases the pathogenesis is related to asbestos and radiation exposure. However cases with no past history of such exposures appear in the literature. One of our two patients has non past history of exposure to asbestos. In both cases the diagnosis was establishes through both biopsy conducted by laparoscopy and ascites fluid cytology. The disease is most common in males over the age of 40. In case of localised disease cytoreductive surgery using hyperthermic intraperitoneal chemotherapy is recommended. Sadly the disease is often unveiled at an advanced stage requiring palliative chemotherapy usually with a platin derivative or in a small percentage of the cases with abdominal radiotherapy to alleviate pain. Prognosis for patients with malignant peritoneal mesothelioma is very poor with a mean survival of 5,4 months versus 12.5 months for pleural mesothelioma. Peritoneal mesothelioma, although rare, should be considered among the differential diagnosis of ascites differential diagnosis work up.}, } @article {pmid21085079, year = {2010}, author = {Bright-Thomas, RJ and Ahmed, RY and Pearson, SB and Muers, MF and Luksza, AR and Turkington, PM}, title = {Pleural mesothelioma presenting as recurrent pneumothoraces.}, journal = {British journal of hospital medicine (London, England : 2005)}, volume = {71}, number = {10}, pages = {590-591}, doi = {10.12968/hmed.2010.71.10.78951}, pmid = {21085079}, issn = {1750-8460}, mesh = {Adult ; Aged ; Asbestos/toxicity ; Diagnosis, Differential ; Humans ; Male ; Mesothelioma/*complications/diagnosis ; Middle Aged ; Occupational Exposure/adverse effects ; Pleural Neoplasms/*complications/diagnosis ; Pneumothorax/diagnosis/*etiology ; Thoracoscopy ; Tomography, X-Ray Computed ; }, } @article {pmid21079518, year = {2011}, author = {Shiba, N and Kusumoto, M and Tsuta, K and Watanabe, H and Watanabe, S and Tochigi, N and Arai, Y}, title = {A case of malignant pleural mesothelioma with osseous and cartilaginous differentiation.}, journal = {Journal of thoracic imaging}, volume = {26}, number = {1}, pages = {W30-2}, doi = {10.1097/RTI.0b013e3181f461a8}, pmid = {21079518}, issn = {1536-0237}, mesh = {Aged ; Bone and Bones/pathology ; Cartilage/pathology ; Cell Differentiation ; Humans ; Male ; Mesothelioma/complications/diagnosis/*diagnostic imaging ; Pleural Neoplasms/complications/diagnosis/*diagnostic imaging/secondary ; Tomography, X-Ray Computed ; }, abstract = {A 69-year-old man with a history of exposure to asbestos was admitted because of a chest radiographic abnormality. Subsequent findings from computed tomography and a thoracoscopic biopsy suggested malignant mesothelioma. Punctate calcification was observed in the pleural tumor on computed tomography scanning. The patient underwent pleuropneumonectomy, and the tumor was pathologically diagnosed as malignant mesothelioma, sarcomatoid type with osseous and cartilaginous differentiation. Malignant mesothelioma with osseous and cartilaginous differentiation is a rare condition. Punctate calcification in the pleural mass as a lesion distinct from the pleural plaque may indicate osseous or osteosarcomatous differentiation in malignant mesothelioma.}, } @article {pmid21059834, year = {2010}, author = {McDonald, JC}, title = {Epidemiology of malignant mesothelioma--an outline.}, journal = {The Annals of occupational hygiene}, volume = {54}, number = {8}, pages = {851-857}, doi = {10.1093/annhyg/meq076}, pmid = {21059834}, issn = {1475-3162}, mesh = {Air Pollutants, Occupational/toxicity ; Aluminum Silicates/toxicity ; Asbestos/toxicity ; Asbestos, Amphibole/toxicity ; Canada/epidemiology ; Carcinogens/toxicity ; Case-Control Studies ; Cohort Studies ; Humans ; Italy/epidemiology ; Lung Neoplasms/chemically induced/*epidemiology ; Mesothelioma/chemically induced/*epidemiology ; Mineral Fibers/toxicity ; Mining ; North America/epidemiology ; Occupational Diseases/chemically induced/*epidemiology ; Occupational Exposure/statistics & numerical data ; Risk Factors ; South Africa/epidemiology ; United Kingdom ; United States/epidemiology ; }, abstract = {In the 1960s and 1970s, well designed case-referent studies put beyond doubt that exposure to airborne asbestos fibres was a cause of malignant mesothelioma. Some 35 cohort mortality studies in a large variety of industries during the 20-year period, 1974-1994, showed a wide range of outcomes, but in general that the risk was higher in exposures which included amphiboles rather than chrysotile alone. Real progress began, however, with discoveries along several lines: the link between pleural changes and mineralogy, the concept and importance of biopersistence, the developments in counting and typing mineral fibres in lung tissue, and data on amphibole mining in South Africa and Australia for comparison with that on chrysotile in Canada and Italy. This led to the recognition of the potential contamination in North America of chrysotile with tremolite. A survey in Canada in 1980-1988 and other surveys demonstrated that crocidolite, amosite, and tremolite could explain almost all cases of mesothelioma. Effective confirmation of this was finally achieved with data on vermiculite miners in Libby, Montana, in the years 1983-1999, where exposure was to tremolite-actinolite and/or other amphibole fibres alone.}, } @article {pmid21041073, year = {2011}, author = {Hirayama, N and Tabata, C and Tabata, R and Maeda, R and Yasumitsu, A and Yamada, S and Kuribayashi, K and Fukuoka, K and Nakano, T}, title = {Pleural effusion VEGF levels as a prognostic factor of malignant pleural mesothelioma.}, journal = {Respiratory medicine}, volume = {105}, number = {1}, pages = {137-142}, doi = {10.1016/j.rmed.2010.10.010}, pmid = {21041073}, issn = {1532-3064}, mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Female ; Humans ; Male ; Mesothelioma/*metabolism/mortality ; Pleural Effusion/*metabolism ; Pleural Neoplasms/*metabolism/mortality ; Prognosis ; Survival Rate ; Vascular Endothelial Growth Factor A/*analysis ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive malignant tumor of mesothelial origin associated with asbestos exposure. MPM has a limited response to conventional chemotherapy and radiotherapy so early diagnosis of MPM is very important. Vascular endothelial growth factor (VEGF), a potent mitogen for the vascular endothelium, is also known to be an autocrine growth factor for MPM. Here, we investigated the pleural effusion VEGF levels in patients with MPM and compared them to those of a population with a non-malignant pleuritis or lung cancer involving malignant pleural effusion.

METHODS: The pleural effusion VEGF concentrations were measured in 46 MPM patients and 45 individuals with non-MPM individuals (25 individuals with non-malignant pleural effusions, and 20 individuals with lung cancer involving malignant pleural effusion).

RESULTS: We demonstrated that patients with MPM had significantly higher pleural effusion VEGF levels than a population with non-malignant pleuritis or lung cancer involving malignant pleural effusion, and the patients with advanced stage MPM showed higher levels of VEGF than the early stage MPM patients. The difference in overall survival between the groups with pleural effusion VEGF levels lower and higher than the assumed cut-off of 2000pg/ml was significant.

CONCLUSIONS: Our data suggest that the pleural effusion VEGF concentration could be useful as an aid for the diagnosis of MPM and as a prognostic factor.}, } @article {pmid21038142, year = {2010}, author = {Yıldırım, H and Metintaş, M and Ak, G}, title = {Malignant pericardial mesothelioma following thoracal radiotherapy; dissemination from pericardium to pleura.}, journal = {Tuberkuloz ve toraks}, volume = {58}, number = {3}, pages = {301-305}, pmid = {21038142}, issn = {2980-3187}, mesh = {Adult ; Diagnosis, Differential ; Fatal Outcome ; Heart Neoplasms/diagnosis/*etiology/pathology ; Humans ; Male ; Mesothelioma/diagnosis/*etiology/pathology ; Neoplasms, Radiation-Induced/diagnosis/*etiology/pathology ; Pericardium/pathology ; Prognosis ; Radiotherapy/*adverse effects ; }, abstract = {Malignant pericardial mesothelioma (MPeM) is a rare, primary pericardial tumor of mesodermal-origin. With respect to the etiology of MPeM, a history of exposure to asbestos has not been clearly demonstrated. MPeM is difficult to diagnose because of the non-specificity of the clinical complaints and symptoms. A known effective treatment does not exist and the prognosis is poor. In this case study, the possible etiologies of MPeM are discussed based on the extant literature. We report herein a patient with MPeM and no history of asbestos exposure who had chemo-radiotherapy for non-Hodgkin's lymphoma, and in whom a tumor spread from the pericardium through the pleura.}, } @article {pmid20961188, year = {2011}, author = {Park, EK and Johnson, AR and Yates, DH and Thomas, PS}, title = {Evaluation of ovarian cancer biomarkers in subjects with benign asbestos-related pleural diseases.}, journal = {Clinical chemistry and laboratory medicine}, volume = {49}, number = {1}, pages = {147-150}, doi = {10.1515/CCLM.2011.015}, pmid = {20961188}, issn = {1437-4331}, mesh = {Aged ; Asbestos/*poisoning ; Biomarkers, Tumor/*blood ; Female ; Humans ; Insulin-Like Growth Factor II/metabolism ; Leptin/blood ; Male ; Middle Aged ; Ovarian Neoplasms/*blood/pathology ; Pleural Diseases/*blood/*etiology/pathology ; Vascular Endothelial Growth Factor A/blood ; }, abstract = {BACKGROUND: Mesothelioma and ovarian cancer have been reported to have a similar pathogenesis, and for this reason it was hypothesized that there may be biomarkers in common and possibly associated with benign pleural diseases caused by asbestos exposure.

METHODS: Serum biomarkers including insulin-like growth factor-II (IGF-II), leptin, prolactin and vascular endothelial growth factor (VEGF) were measured in an observational study of subjects with benign asbestos-related pleural diseases (BARPD) (n=24) and healthy subjects with an asbestos exposure history (n=12).

RESULTS: Mean serum IGF-II and VEGF concentration in healthy subjects with a history of asbestos exposure were higher than those with BARPD. Mean serum concentrations of leptin and prolactin showed opposite trends when compared to IGF-II and VEGF concentrations among these groups.

CONCLUSIONS: The results suggest that IGF-II and VEGF concentrations are lower in BARPD, similar to studies of ovarian cancer. This finding warrants further investigation with malignant asbestos-related diseases.}, } @article {pmid20959396, year = {2010}, author = {Mirabelli, D and Cavone, D and Merler, E and Gennaro, V and Romanelli, A and Mensi, C and Chellini, E and Nicita, C and Marinaccio, A and Magnani, C and Musti, M}, title = {Non-occupational exposure to asbestos and malignant mesothelioma in the Italian National Registry of Mesotheliomas.}, journal = {Occupational and environmental medicine}, volume = {67}, number = {11}, pages = {792-794}, doi = {10.1136/oem.2009.047019}, pmid = {20959396}, issn = {1470-7926}, mesh = {Adult ; Aged ; Asbestos/*toxicity ; Environmental Exposure/*adverse effects/statistics & numerical data ; Family Health ; Female ; Humans ; Industry/statistics & numerical data ; Italy/epidemiology ; Male ; Mesothelioma/epidemiology/*etiology ; Middle Aged ; Registries ; }, abstract = {BACKGROUND: Malignant mesotheliomas are strictly related to asbestos, but in a proportion of cases no exposure can be recalled. Published estimates of this proportion have important variations. Historical and geographical differences in the fraction of cancer due to any given exposure are to be expected, but incomplete identification of non-occupational exposures may have played a role.

METHODS: To assess the role of non-occupational exposures in causing malignant mesotheliomas in Italy, the exposures of cases registered by the national mesothelioma registry (ReNaM) were examined. ReNaM started in 1993 in five regions and currently covers 98% of the Italian population. Information on occupational and non-occupational exposures of cases is collected whenever possible.

RESULTS: From 1993 to 2001 ReNaM registered 5173 malignant mesothelioma cases, and exposures were assessed in 3552 of them. 144 and 150 cases with exposures limited to environmental (living in the neighbourhood of an industrial or natural source of asbestos) or familial (living with a person occupationally exposed to asbestos) circumstances, respectively, were identified, accounting for 8.3% of all cases.

CONCLUSIONS: Geographical variations in the proportion of cases due to non-occupational exposures may be explained by the past distribution of asbestos-using industries.}, } @article {pmid20957726, year = {2010}, author = {Harding, AH and Darnton, AJ}, title = {Asbestosis and mesothelioma among British asbestos workers (1971-2005).}, journal = {American journal of industrial medicine}, volume = {53}, number = {11}, pages = {1070-1080}, doi = {10.1002/ajim.20844}, pmid = {20957726}, issn = {1097-0274}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Asbestosis/*mortality ; Cause of Death ; Female ; Humans ; International Classification of Diseases ; Male ; Mesothelioma/classification/*mortality ; Middle Aged ; Neoplasms/mortality ; Occupational Exposure/*adverse effects ; Registries ; Regression Analysis ; Risk ; Risk Factors ; Time Factors ; United Kingdom/epidemiology ; Young Adult ; }, abstract = {BACKGROUND: Ascertainment of asbestosis and mesothelioma from underlying cause of death underestimates the burden of these diseases. The aims of this study were to estimate the true frequency of asbestosis and mesothelioma among asbestos workers in Great Britain (GB), and to identify factors associated with the risk of death with these diseases.

METHODS: The GB Asbestos Survey was established in 1971 to monitor long-term health outcomes among workers covered by regulations to control asbestos at work. Asbestosis and mesothelioma cases were defined by multiple cause of death, and were ascertained by identifying asbestos workers on the GB Asbestosis and Mesothelioma Registers. Standardized mortality ratios (SMRs) were calculated; the risks of asbestosis and mesothelioma were modeled with Poisson regression analysis. Deaths to the end of 2005 were included.

RESULTS: There were 15,557 deaths between 1971 and 2005 among the 98,912 workers. Altogether 477 asbestosis and 649 mesothelioma cases were identified. The SMR for all causes was 1.42, for asbestosis 51.3, and for mesothelioma 13.5. In multiply adjusted analysis, age, sex, job, and birth cohort were significantly associated with asbestosis and mesothelioma. For asbestosis year of first exposure, and for mesothelioma latency, were also statistically significant.

CONCLUSIONS: The asbestos workers experienced high mortality from all causes, asbestosis, and mesothelioma. There was some evidence that the risk of asbestosis and mesothelioma was lower in later birth cohorts and among those first occupationally exposed to asbestos more recently. Due to the long latency of both diseases, further follow-up is required to confirm these trends.}, } @article {pmid20956618, year = {2010}, author = {Kao, SC and Pavlakis, N and Harvie, R and Vardy, JL and Boyer, MJ and van Zandwijk, N and Clarke, SJ}, title = {High blood neutrophil-to-lymphocyte ratio is an indicator of poor prognosis in malignant mesothelioma patients undergoing systemic therapy.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {16}, number = {23}, pages = {5805-5813}, doi = {10.1158/1078-0432.CCR-10-2245}, pmid = {20956618}, issn = {1557-3265}, mesh = {Adult ; Aged ; Algorithms ; Female ; Health Status Indicators ; Humans ; Leukocyte Count ; Lymphocytes/*pathology ; Male ; Mesothelioma/*diagnosis/mortality/pathology/*therapy ; Middle Aged ; Neoplasm Staging ; Neutrophils/*pathology ; Pleural Neoplasms/*diagnosis/mortality/pathology/*therapy ; Predictive Value of Tests ; Prognosis ; Retrospective Studies ; Survival Analysis ; }, abstract = {PURPOSE: Asbestos-induced chronic inflammation is implicated in the pathogenesis of malignant mesothelioma (MM). We have investigated blood neutrophil-to-lymphocyte ratio (NLR), an index of systemic inflammation, as a prognostic factor in MM patients.

EXPERIMENTAL DESIGN: Patients with MM who had systemic therapy at participating institutes were studied. Potential prognostic factors such as age, gender, performance status, histologic subtype, and baseline laboratory parameters, including NLR, were analyzed. Overall survival from commencement of therapy was determined by the Kaplan-Meier method. Multivariate analyses using Cox Regression model were performed with significant factors (P ≤ 0.05) to determine their independent effect.

RESULTS: A total of 173 MM patients undergoing systemic therapy including 119 patients receiving first-line therapy and 54 patients receiving second- or third-line therapy were included in this retrospective evaluation. Forty-two percent of patients had an elevated NLR at baseline. The following variables were predictive of survival: female gender (P = 0.044), epithelioid histologic subtype (P < 0.001), baseline white blood cell count less than 8.3 × 10⁹/L (P = 0.008), baseline platelet count 400 × 10⁹/L or less (P = 0.05), and NLR of 5 or less (P < 0.001). After multivariate analysis, histologic epithelioid subtype [hazard ratio (HR) = 2.0; 95% confidence interval (CI) = 1.3-2.9; P = 0.001], and NLR less than 5 (HR = 2.7; 95% CI = 1.8-3.9; P < 0.001) remained independent predictors. The 1-year survival rate was 60% versus 26%, whereas the 2-year survival rate was 34% versus 10% for NLR less than 5 and 5 or greater, respectively. In the separate analyses of chemotherapy-naive and previously treated patient groups, NLR was an independent predictor of survival in both groups.

CONCLUSION: Our results indicate that NLR is an independent predictor of survival for patients with MM undergoing systemic therapy.}, } @article {pmid20949774, year = {2010}, author = {Dhalluin, X and Scherpereel, A}, title = {Treatment of malignant pleural mesothelioma: current status and future directions.}, journal = {Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace}, volume = {73}, number = {2}, pages = {79-85}, doi = {10.4081/monaldi.2010.302}, pmid = {20949774}, issn = {1122-0643}, mesh = {Combined Modality Therapy ; Humans ; Mesothelioma/pathology/*therapy ; Pleural Neoplasms/pathology/*therapy ; }, abstract = {Previously considered to be rare, malignant pleural mesothelioma (MPM) is a highly aggressive tumour that has become a very important issue over recent years due to its poor prognosis and its increasing incidence mostly linked to previous asbestos exposure. An optimal treatment for MPM is not established yet; new therapies and predictive tools are still needed in the management of this cancer. Thus the aim of this review is to provide clinicians clear and up-to-dated data on the latest therapeutic strategies for MPM patients in 2010. The guidelines recently proposed by the European Respiratory Society (ERS) and the European Society of Thoracic Surgeons (ESTS) taskforce are summarized here. The authors also briefly reviewed the future directions in MPM treatment including targeted therapies, gene or cell therapies.}, } @article {pmid20948267, year = {2010}, author = {Noguchi, T and Kawamura, M and Kawamura, T and Shimamura, T and Sasaki, K and Hosono, T and Sato, R and Murakami, K}, title = {[A case of diffuse peritoneal malignant mesothelioma--intraabdominal administration of cisplatin is useful for diminishing ascites].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {37}, number = {10}, pages = {1975-1978}, pmid = {20948267}, issn = {0385-0684}, mesh = {Antineoplastic Agents/*therapeutic use ; Cisplatin/administration & dosage/*therapeutic use ; Fatal Outcome ; Humans ; Infusions, Parenteral ; Male ; Mesothelioma/diagnostic imaging/*drug therapy/pathology ; Middle Aged ; Peritoneal Neoplasms/diagnostic imaging/*drug therapy/pathology ; Radiography ; }, abstract = {A 59-year-old man with a history of exposure to asbestos suffered from abdominal distension and visited our hospital. Abdominal CT revealed vast ascites but there was no obvious primary lesion. Serum tumor markers and hyaluronate were within the normal range. Abdominal puncture was carried out, and cytology of ascites was negative. We suspected diffuse malignant peritoneal mesothelioma because hyaluronate in ascites rose to 10×10[4] ng/mL. Ga-scintigraphy and FDG-PET were negative. We performed laparoscopic observation for definite diagnosis and found fine white particles at the peritoneum. The result of biopsy was malignant mesothelioma. The patient underwent intraperitoneal administration of cisplatin and his ascites was diminished. He lived for a year with no recurrence but died 23 months after diagnosis because of progression of pleural mesothelioma and liver metastases. Relapse of ascites was not found in the entire clinical course. Cisplatin administration in the peritoneal cavity is thus very effective in preventing progression of ascites.}, } @article {pmid20933535, year = {2011}, author = {Takata, A and Yamauchi, H and Toya, T and Miyamoto-Kohno, S and Iwatatsu, Y and Teranaka, I and Aminaka, M and Yamashita, K and Kohyama, N}, title = {Effectiveness of serum megakaryocyte potentiating factor in evaluating the effects of chrysotile and its heated products on respiratory organs.}, journal = {Toxicology and applied pharmacology}, volume = {252}, number = {2}, pages = {123-129}, doi = {10.1016/j.taap.2010.09.026}, pmid = {20933535}, issn = {1096-0333}, mesh = {Animals ; Asbestos, Serpentine/metabolism/*toxicity ; Biomarkers/blood ; Drug Evaluation, Preclinical/methods ; GPI-Linked Proteins/*blood ; Hot Temperature ; Lung/*drug effects/*metabolism/pathology ; Male ; Mesothelin ; Rats ; Rats, Wistar ; Silicon Compounds/metabolism/*toxicity ; }, abstract = {Chrysotile (CH), the most common form of asbestos, is rendered less toxic by heating it at 1000°C and converting it to forsterite (FO-1000). However, further safety tests are needed to evaluate human health risk of these materials. It has been reported that serum concentrations of megakaryocyte potentiating factor N-ERC/mesothelin become elevated in patients with mesotheliomas caused by asbestos exposure. In this study, a single 2mg dose of CH or FO-1000 was intratracheally administered to rats. Within 180days after the administrations, serum N-ERC/mesothelin concentrations, levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in lung tissues and pathological changes in respiratory organs were determined. In the CH group, a significant increase in serum N-ERC/mesothelin concentrations was observed immediately after intratracheal administration, and the elevation lasted for 30days. In lung tissues, positive staining for 8-OHdG in bronchioles, alveolar epithelium, inflammatory cells, and granulomas was evidence of a marked DNA oxidative damage. Furthermore, measurements of 8-OHdG in lung tissues based on the HPLC-ECD method suggested that serum N-ERC/mesothelin concentrations tended to increase when there are significant DNA damages in lung tissues. In contrast, in the FO-1000 group, a marked rise in serum N-ERC/mesothelin concentrations occurred only in the early phase (1-7days) after intratracheal administration. Similarly, FO-1000 induced elevation of 8-OHdG in lung tissues was transient and modest compared with those of the CH-treated animals. In both the CH and FO-1000 groups, we observed significant correlations between serum N-ERC/mesothelin concentrations and lung 8-OHdG concentrations (r=0.559, p=0.001 for the CH group; r=0.516, p=0.01 for the FO-1000 group). In summary, we demonstrated the possibility of using serum N-ERC/mesothelin concentrations as a useful biomarker for early phase exposure to either CH or FO-1000.}, } @article {pmid20924566, year = {2010}, author = {de Gennaro, G and Dragonieri, S and Longobardi, F and Musti, M and Stallone, G and Trizio, L and Tutino, M}, title = {Chemical characterization of exhaled breath to differentiate between patients with malignant plueral mesothelioma from subjects with similar professional asbestos exposure.}, journal = {Analytical and bioanalytical chemistry}, volume = {398}, number = {7-8}, pages = {3043-3050}, doi = {10.1007/s00216-010-4238-y}, pmid = {20924566}, issn = {1618-2650}, mesh = {Aged ; Aged, 80 and over ; Asbestos/*poisoning ; Breath Tests/*methods ; Case-Control Studies ; Cross-Sectional Studies ; Discriminant Analysis ; Gas Chromatography-Mass Spectrometry/methods ; Humans ; Mesothelioma/diagnosis/etiology/*metabolism ; Middle Aged ; Neural Networks, Computer ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/diagnosis/etiology/*metabolism ; Principal Component Analysis ; Volatile Organic Compounds/*analysis ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive tumour whose main aetiology is the long-term exposure to asbestos fibres. The diagnostic procedure of MPM is difficult and often requires invasive approaches; therefore, it is clinically important to find accurate markers for MPM by new noninvasive methods that may facilitate the diagnostic process and identify patients at an earlier stage. In the present study, the exhaled breath of 13 patients with histology-established diagnosis of MPM, 13 subjects with long-term certified professional exposure to asbestos (EXP) and 13 healthy subjects without exposure to asbestos (healthy controls, HC) were analysed. An analytical procedure to determine volatile organic compounds by sampling of air on a bed of solid sorbent and thermal desorption GC-MS analysis was developed in order to identify the compounds capable of discriminating among the three groups. The application of univariate (ANOVA) and multivariate statistical treatments (PCA, DFA and CP-ANN) showed that cyclopentane and cyclohexane were the dominant variables able to discriminate among the three groups. In particular, it was found that cyclohexane is the only compound able to differentiate the MPM group from the other two; therefore, it can be a possible marker of MPM. Cyclopentane is the dominant compound in the discrimination between EXP and the other groups (MPM and HC); then, it can be considered a good indicator for long-term asbestos exposure. This result suggests the need to perform frequent and thorough investigations on people exposed to asbestos in order to constantly monitor their state of health or possibly to study the evolution of disease over time.}, } @article {pmid20886529, year = {2010}, author = {Rolland, P and Gramond, C and Lacourt, A and Astoul, P and Chamming's, S and Ducamp, S and Frenay, C and Galateau-Salle, F and Ilg, AG and Imbernon, E and Le Stang, N and Pairon, JC and Goldberg, M and Brochard, P and , }, title = {Occupations and industries in France at high risk for pleural mesothelioma: A population-based case-control study (1998-2002).}, journal = {American journal of industrial medicine}, volume = {53}, number = {12}, pages = {1207-1219}, doi = {10.1002/ajim.20895}, pmid = {20886529}, issn = {1097-0274}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Carcinogens/*toxicity ; Case-Control Studies ; Confidence Intervals ; Female ; France/epidemiology ; Humans ; *Industry ; Male ; Mesothelioma/*epidemiology/etiology/prevention & control ; Middle Aged ; Occupational Diseases/*epidemiology/etiology/prevention & control ; Occupational Exposure/*adverse effects ; Occupational Health/statistics & numerical data ; Pleural Neoplasms/*epidemiology/etiology/prevention & control ; Population Surveillance ; Risk Assessment ; Sex Factors ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Occupational exposure to asbestos, widely used in various industries for decades, is the most important risk factor for pleural mesothelioma. We report here the ranking of occupations and industries in France at high risk for this cancer among men and women.

METHODS: A population-based case-control study, conducted from 1998 to 2002, included 462 cases (80.3% men) and 897 controls. Data were collected in face-to-face interviews with a standardized questionnaire. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each occupation and industry; subjects never employed in each category were the reference.

RESULTS: For men, risks were high for several occupations and industries. Besides the expected high risks for non-metallic mineral product makers and manufacturing asbestos products, occupations such as plumbers (OR = 5.57, 95% CI: 2.90-10.69), sheet-metal workers, welders, metal molders, coremakers, and cabinetmakers were also at high risk. Elevated risks were found in the industries of shipbuilding (OR = 9.13, 95% CI: 5.20-16.06) and construction, but also in the manufacturing of metal products, chemicals, and railroad and aircraft equipment. The results for women showed increased but not significant risks in several occupational activities.

CONCLUSIONS: This report provides new insight into the epidemiology of mesothelioma, confirming risks for occupational activities reported earlier and pointing out risks in activities never previously reported. It offers guidance to authorities for the compensation of asbestos victims and for prevention in at-risk activities still involving asbestos-containing products.}, } @article {pmid20885075, year = {2010}, author = {Kumagai, N and Nishimura, Y and Maeda, M and Hayashi, H and Otsuki, T}, title = {[Immunological effects of silica/asbestos].}, journal = {Nihon eiseigaku zasshi. Japanese journal of hygiene}, volume = {65}, number = {4}, pages = {493-499}, doi = {10.1265/jjh.65.493}, pmid = {20885075}, issn = {0021-5082}, mesh = {Asbestos/*adverse effects ; Autoimmunity/*drug effects ; Carrier Proteins ; Humans ; Lung Neoplasms/immunology ; Mesothelioma/immunology ; NLR Family, Pyrin Domain-Containing 3 Protein ; Phagocytes/immunology ; Silicon Dioxide/*adverse effects ; Silicosis/immunology ; T-Lymphocytes, Regulatory/immunology ; Tumor Escape/immunology ; }, abstract = {Silica and asbestos cause pneumoconioses known as silicosis and asbestosis, respectively, that are each characterized by progressive pulmonary fibrosis. On the other hand, silicosis patients often suffer from a type of immunological dysregulation that gives rise to autoimmunity. These epidemiological findings suggest that silica may affect the immune system in humans. In addition, as asbestos itself is a mineral silicate, it may possess generalized immunotoxicological effects similar to those associated with silica particles. Because asbestos-exposed patients are well-known to often develop malignant diseases such as lung cancer and mesothelioma, one silica-like dysregulatory outcome that needs to be considered (apart from autoimmunity) is an alteration in host tumor immunity. In this review, the immunotoxicological effects of both silica and asbestos are presented and discussed in terms of immune system dysregulation as manifested by the onset of autoimmunity or alterations in host tumor immunity.}, } @article {pmid20878622, year = {2010}, author = {Cristaudo, A and Foddis, R and Bonotti, A and Simonini, S and Vivaldi, A and Guglielmi, G and Ambrosino, N and Canessa, PA and Chella, A and Lucchi, M and Mussi, A and Mutti, L}, title = {Comparison between plasma and serum osteopontin levels: usefulness in diagnosis of epithelial malignant pleural mesothelioma.}, journal = {The International journal of biological markers}, volume = {25}, number = {3}, pages = {164-170}, doi = {10.1177/172460081002500307}, pmid = {20878622}, issn = {1724-6008}, mesh = {Aged ; Asbestos/*adverse effects ; Biomarkers, Tumor/*blood ; Blood Preservation/methods ; Blood Specimen Collection ; Cryopreservation ; Enzyme-Linked Immunosorbent Assay ; Epithelium/pathology ; Female ; Humans ; Male ; Mesothelioma/*blood/etiology ; Middle Aged ; Occupational Diseases/blood/etiology ; Occupational Exposure ; Osteopontin/*blood ; Plasma ; Pleural Neoplasms/*blood/etiology ; Respiration Disorders/blood ; Serum ; Smoking/blood ; *Specimen Handling ; Temperature ; }, abstract = {BACKGROUND: A potential role of serum osteopontin (OPN) and serum mesothelin-related peptide (SMRP) in the diagnosis of malignant pleural mesothelioma (MPM) has been recently reported. Although the most important data regarding the role of OPN in MPMs derive from the marker's measurement in serum samples, most commercial laboratory kits for OPN assay are suitable only for measuring plasma levels, as indicated by the manufacturers. Our study aimed to evaluate the influence of preanalytic variables on serum and plasma OPN, to compare serum and plasma OPN in the same population, and to assess whether OPN levels can aid in the diagnostic distinction of patients with MPM versus benign respiratory disease (BRD) and healthy subjects exposed to asbestos.

METHODS: The influence of preanalytic variables such as the length of storage at different temperatures and the number of thawings of samples on serum and plasma OPN measurements were evaluated. We measured OPN in 239 plasma samples from 207 asbestos-exposed subjects including 94 healthy controls and 113 subjects with BRD, and 32 patients with epithelial MPM, employing a commercially available ELISA. Serum OPN was measured in 196 of the same 239 samples from 80 healthy subjects, 92 BRD patients and 24 MPM patients.

RESULTS: We found that both serum and plasma OPN levels were influenced by storage at -80°C and by the number of thawings, while serum OPN was influenced also by storage at room temperature. Plasma and serum OPN levels were significantly higher (p<0.0001) in patients with epithelial MPM than in the healthy control group and the BRD group. The application of a ROC curve for plasma OPN resulted in an AUC value of 0.780 with a best cutoff of 878.65 ng/mL, with a sensitivity of 68.8% and a specificity of 84.5%. The AUC for sOPN was 0.725 with a best cutoff of 16.06 ng/mL, with a sensitivity of 62.5% and a specificity of 87.3%. Within the control group no significant correlation was observed between age, duration of asbestos exposure, pack-years in current smokers, lung function or imaging parameters and plasma or serum OPN.

CONCLUSIONS: These data suggest that plasma OPN and serum OPN are not influenced by confounding factors such as age, smoking habits and asbestos exposure. Plasma and serum OPN may be useful markers in the diagnosis of epithelial MPM in addition to traditional radiological exams. However, in our opinion plasma OPN is preferable to serum OPN because it is more stable and measurements of OPN in serum are less reliable.}, } @article {pmid20870754, year = {2011}, author = {Varani, K and Maniero, S and Vincenzi, F and Targa, M and Stefanelli, A and Maniscalco, P and Martini, F and Tognon, M and Borea, PA}, title = {A3 receptors are overexpressed in pleura from patients with mesothelioma and reduce cell growth via Akt/nuclear factor-κB pathway.}, journal = {American journal of respiratory and critical care medicine}, volume = {183}, number = {4}, pages = {522-530}, doi = {10.1164/rccm.201006-0980OC}, pmid = {20870754}, issn = {1535-4970}, mesh = {Adult ; Apoptosis ; Asbestos, Crocidolite ; Blotting, Western ; Cell Proliferation ; Cells, Cultured ; Female ; Humans ; Male ; Mesothelioma/*metabolism/*pathology ; Middle Aged ; NF-kappa B/*metabolism ; Pleura/metabolism/pathology ; Pleural Neoplasms/*metabolism/*pathology ; Proto-Oncogene Proteins c-akt/*metabolism ; Receptor, Adenosine A3/*metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Up-Regulation ; }, abstract = {RATIONALE: A strong link has been established between exposure to asbestos and increased risk for pleural malignant mesothelioma (MM). Adenosine plays a key role in inflammatory processes and cancer, where it is involved in the regulation of cell death and proliferation.

OBJECTIVES: The primary aim of this study was to investigate the presence of adenosine receptors (ARs) in human MM pleura (MMP) and healthy mesothelial pleura (HMP). To shed some light on the interaction between adenosine and MM, the presence and functionality of ARs were explored in human healthy mesothelial cells (HMC) and in malignant mesothelioma cells (MMC).

METHODS: ARs were analyzed by using reverse transcriptase-polymerase chain reaction, Western blotting, and saturation binding assays. HMC were treated with crocidolite asbestos, which is the principal risk factor for MM. The role of A₃ ARs on these cellular models, evaluating cAMP production, Akt phosphorylation, and nuclear factor (NF)-κB activation, was investigated. The dual effect of A₃AR stimulation on healthy and cancer cell growth was studied by means of proliferation, apoptosis, and cytotoxicity assays.

MEASUREMENTS AND MAIN RESULTS: A₃AR was up-regulated by 2.5-fold (P < 0.01) in MMP when compared with HMP. Stimulation of A₃ARs decreased proliferation and exerted a cytotoxic and proapoptotic effect on MMC and on HMC exposed to asbestos and tumor necrosis factor-α, but not on HMC with an involvement of the deregulation of Akt/NF-κB cell survival pathway.

CONCLUSIONS: These new findings suggest that A₃AR could represent a pharmacological target to prevent tumor development after asbestos exposure and to treat full-blown MM.}, } @article {pmid20860524, year = {2010}, author = {Aschberger, K and Johnston, HJ and Stone, V and Aitken, RJ and Hankin, SM and Peters, SA and Tran, CL and Christensen, FM}, title = {Review of carbon nanotubes toxicity and exposure--appraisal of human health risk assessment based on open literature.}, journal = {Critical reviews in toxicology}, volume = {40}, number = {9}, pages = {759-790}, doi = {10.3109/10408444.2010.506638}, pmid = {20860524}, issn = {1547-6898}, mesh = {Asbestos/toxicity ; Environmental Health ; Humans ; *Inhalation Exposure ; Mesothelioma/chemically induced ; Nanotubes, Carbon/*toxicity ; *Occupational Exposure ; Risk Assessment ; }, abstract = {Carbon nanotubes (CNTs) possess many unique electronic and mechanical properties and are thus interesting for numerous novel industrial and biomedical applications. As the level of production and use of these materials increases, so too does the potential risk to human health. This study aims to investigate the feasibility and challenges associated with conducting a human health risk assessment for carbon nanotubes based on the open literature, utilising an approach similar to that of a classical regulatory risk assessment. Results indicate that the main risks for humans arise from chronic occupational inhalation, especially during activities involving high CNT release and uncontrolled exposure. It is not yet possible to draw definitive conclusions with regards the potential risk for long, straight multi-walled carbon nanotubes to pose a similar risk as asbestos by inducing mesothelioma. The genotoxic potential of CNTs is currently inconclusive and could be either primary or secondary. Possible systemic effects of CNTs would be either dependent on absorption and distribution of CNTs to sensitive organs or could be induced through the release of inflammatory mediators. In conclusion, gaps in the data set in relation to both exposure and hazard do not allow any definite conclusions suitable for regulatory decision-making. In order to enable a full human health risk assessment, future work should focus on the generation of reliable occupational, environmental and consumer exposure data. Data on toxicokinetics and studies investigating effects of chronic exposure under conditions relevant for human exposure should also be prioritised.}, } @article {pmid20857142, year = {2010}, author = {Matsuyama, A and Hisaoka, M and Iwasaki, M and Iwashita, M and Hisanaga, S and Hashimoto, H}, title = {TLE1 expression in malignant mesothelioma.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {457}, number = {5}, pages = {577-583}, pmid = {20857142}, issn = {1432-2307}, mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Co-Repressor Proteins ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; Male ; Mesothelioma/*metabolism/*pathology ; Middle Aged ; Repressor Proteins/*biosynthesis ; Sarcoma, Synovial/pathology ; }, abstract = {Malignant mesothelioma, an aggressive and often lethal tumor commonly associated with asbestos exposure, has been morphologically classified into epithelial, biphasic, and sarcomatoid subtypes. Histological distinction between biphasic or sarcomatoid mesothelioma and synovial sarcoma may be problematic in certain circumstances of intrathoracic location because of their similar clinicopathologic features, including not only their morphology but also occasional positive immunoreaction of mesothelioma markers. TLE1, which plays an important role in Wnt pathway, has been shown to be a specific marker for synovial sarcoma and diagnostically is useful; however, TLE1 expression in malignant mesotheliomas has not been fully evaluated. We immunohistochemically examined the expression of TLE1, factors related to the Wnt pathway including β-catenin and cyclin D1, and mesothelioma markers including calretinin, HBME-1, cytokeratin 5/6, and thrombomodulin in 29 malignant mesotheliomas. TLE1 was variably expressed in 28 malignant mesotheliomas regardless of histomorphological subtype with >25% of positive cells in 20 cases (69.0%). There was no evidence of association of TLE1 expression with immunoreactivity to other markers. Our study showed no or limited value of the immunohistochemical TLE1 expression in distinguishing malignant mesothelioma and synovial sarcoma.}, } @article {pmid20853780, year = {2009}, author = {Zavalić, M and Macan, J}, title = {[Croatian and international regulations on the protection and rights of workers exposed to asbestos at work].}, journal = {Arhiv za higijenu rada i toksikologiju}, volume = {60 Suppl}, number = {}, pages = {57-63}, pmid = {20853780}, issn = {0004-1254}, mesh = {Asbestos/*adverse effects ; Asbestosis/diagnosis/prevention & control ; Croatia ; European Union ; Humans ; International Agencies ; Occupational Exposure/*legislation & jurisprudence ; Occupational Health/*legislation & jurisprudence ; Workers' Compensation/legislation & jurisprudence ; }, abstract = {New regulations on the protection and rights of workers occupationally exposed to asbestos were introduced in Croatia in 2007 and 2008. They have been harmonised with the European Union (EU) and International Labour Organization (ILO) regulations, and make a step forward in safety at work, health protection, social rights, and pension schemes for Croatian workers occupationally exposed to asbestos. The 2007 Croatian regulation on the protection of workers from the risks related to exposure to asbestos at work defines and describes activities in which workers can be occupationally exposed to asbestos, defines the threshold value of asbestos in the air at work, defines valid methods for measurement of asbestos concentrations in the air, and establishes measures to reduce asbestos exposure at work or protect the exposed workers. Croatian law regulating obligatory health surveillance of workers occupationally exposed to asbestos from year 2007 defines activities and competent authorities to implement health surveillance of workers occupationally exposed to asbestos and to diagnose occupational diseases related to asbestos. This law also defines "occupational exposure to asbestos", and "occupational asbestos-related diseases", including asbestosis (pulmonary asbestos-related fibrosis), pleural asbestos-related disorders (plaques, pleural thickening, and benign effusion), lung and bronchial cancer, and malignant mesothelioma of serous membranes. These regulations have been harmonised with ILO, Directive 2003/18/EC amending Council Directive 83/477/EEC on the protection of workers from the risks related to exposure to asbestos at work, and with the Commission Recommendation 2003/670/EC concerning the European schedule of occupational diseases. The 2008 Croatian regulation on conditions of health surveillance, diagnostic procedures and criteria for confirmation of occupational asbestos-related diseases "defines the terms and the content of medical examination of workers exposed to asbestos, and criteria for the confirmation of occupational asbestos-related diseases which are harmonised with the Helsinki criteria acknowledged by ILO and EU, particularly concerning the level and length of exposure. Croatian law on compensation of workers occupationally exposed to asbestos from 2007 regulates compensation claims for workers with occupational asbestos-related disease, authorities competent to process these claims, and funds and coefficients for compensation payments. Accordingly, Croatia is responsible for compensation claims payment for workers with occupational asbestos-related disease. The 2007 law on conditions for entitlement to full pension for workers exposed to asbestos at work defines the conditions for fulfilling criteria for retirement pension for workers exposed to asbestos at work.}, } @article {pmid20853778, year = {2009}, author = {Kanceljak-Macan, B}, title = {[Immunological aspects of asbestos-related diseases].}, journal = {Arhiv za higijenu rada i toksikologiju}, volume = {60 Suppl}, number = {}, pages = {45-50}, pmid = {20853778}, issn = {0004-1254}, mesh = {Asbestos/adverse effects/*immunology ; Asbestosis/*immunology ; Humans ; Mesothelioma/etiology/genetics/*immunology ; Pleural Neoplasms/etiology/genetics/*immunology ; }, abstract = {Asbestos is a generic name for a group of silicate minerals. The most common are chrysotile, crocidolite, amosite, tremolite and anthophyllite. Exposure to asbestos may cause asbestos-related non-malignant diseases of the lung and pleura, including asbestosis, pleural plaques, diffuse pleural fibrosis, small airway disease, and malignant diseases such as lung cancer and malignant mesothelioma. Inhaled asbestos fibres deposit in the distal regions of the respiratory system where they interact with epithelial cells and alveolar macrophages, and trigger active immunological response which leads to a slowly progressing lung fibrosis. Asbestos may affect immunocompetent cells and induce malignant transformation of mesothelial cells. It is still not clear whether asbestos causes mesothelioma directly or indirectly. There is a general opinion that malignant mesothelioma is a complex tumour that results from the accumulation of multiple genetic alterations over many years. There is no specific antibody for malignant mesothelioma as yet which could act as a single diagnostic tool. Recent studies have demonstrated that asbestos acts on peripheral T cells as superantigen and that in malignant mesothelioma patients there is an overexpression of the Bcl-2 gene on peripheral CD4+ T cells. These findings contribute to better understanding of biological effects of asbestos in respect to the duration and intensity of exposure.}, } @article {pmid20853777, year = {2009}, author = {Kricka, O and Matanić Lender, D and Barković, I and Flego, V and Kupanovac, Z and Bulat Kardum, L}, title = {[Malignant pleural mesothelioma in patients hospitalised at the Clinical Hospital Centre Rijeka between 1989 and 2008].}, journal = {Arhiv za higijenu rada i toksikologiju}, volume = {60 Suppl}, number = {}, pages = {41-43}, pmid = {20853777}, issn = {0004-1254}, mesh = {Asbestos/*adverse effects ; Croatia/epidemiology ; Environmental Exposure ; Female ; Humans ; Male ; Mesothelioma/*epidemiology/etiology ; Occupational Diseases/*epidemiology/etiology ; Pleural Neoplasms/*epidemiology/etiology ; }, abstract = {Malignant pleural mesothelioma (MPM) is a relatively rare tumour, mainly associated with occupational exposure to asbestos. We retrospectively analysed the records of MPM patients treated at the Pulmonology Department of the Clinic for Internal Diseases, Clinical Hospital Centre Rijeka between 1989 and 2008. to establish the incidence of MPM in that period. Between 1989 and 2008 the hospital received 121 MPM patients, 117 of whom were men and four women. We observed a continued increase in newly diagnosed MPM patients from year to year. Occupational exposure to asbestos was established in 72 patients who worked in shipbuilding. In our region the incidence of MPM has been rising significantly. We believe that this is not related to improved diagnostics, but to the long latency of the disease. This is why we expect this trend to continue for a while. In the U.S.A. and Europe, MPM incidence is expected to peak by 2020, while in countries with poor control over asbestos use this may take longer.}, } @article {pmid20853776, year = {2009}, author = {Cvitanović, S and Ivancević, Z and Capkun, V and Tenzera-Taslak, G}, title = {[Incidence of malignant pleural mesothelioma in Split-Dalmatia County].}, journal = {Arhiv za higijenu rada i toksikologiju}, volume = {60 Suppl}, number = {}, pages = {31-39}, pmid = {20853776}, issn = {0004-1254}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Croatia/epidemiology ; Environmental Exposure ; Female ; Humans ; Incidence ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Diseases/epidemiology/etiology ; Pleural Neoplasms/*epidemiology/etiology ; }, abstract = {Between 2001 and 2005, 1150 patients with respiratory symptoms were admitted to our Pneumology Clinic whose workplace or residence could involve exposure to asbestos One hundred and twenty (10.4%) patients were confirmed a disease of the lung and/or pleura which could have been asbestos-related. A follow-up of these patients showed that 52 of 120 (43.3%) developed malignant pleural mesothelioma (MPM), but it was also found in 12 of 1030 (1.1%) patients without an asbestos-related disease. Of the 64 patients with MPM, 54 (84.3%) were men and 10 (15.6%) women. Fifty-two (81.2%) were professionally or residentially exposed to asbestos. The incidence ofmesothelioma for the Split-Dalmatia County between 2001 and 2005 was 13.8 per 100,000 inhabitants, while in the whole of Croatia it was 3.9. Mean annual incidence in the Split-Dalmatia County was 2.7 per 100,000 inhabitants, and in the whole of Croatia 0.8. This means that 22.7% of all patients with MPM in Croatia were from the Split-Dalmatia County (whose population is about 10.5% of Croatia's). This distribution of MPM may be related to the strong shipbuilding industry and other asbestos-related industries in this part of the country.}, } @article {pmid20853775, year = {2009}, author = {Decković-Vukres, V and Corić, T and Tomić, B and Erceg, M and Mihel, S and Ivicević Uhernik, A and Pristas, I}, title = {[Incidence and prevalence of asbestos-related diseases in Croatia].}, journal = {Arhiv za higijenu rada i toksikologiju}, volume = {60 Suppl}, number = {}, pages = {23-30}, pmid = {20853775}, issn = {0004-1254}, mesh = {Asbestosis/*epidemiology ; Croatia/epidemiology ; Humans ; Incidence ; Mesothelioma/epidemiology/etiology ; Pleural Neoplasms/*epidemiology/etiology ; Prevalence ; }, abstract = {The aim of this study was to identify the incidence and prevalence of asbestos-related diseases in Croatia, based on the Hospital Morbidity Database and General Mortality Database of the Croatian National Institute of Public Health. Both databases cover a period from 2002 to 2007), and include information from the Register of Occupational Diseases. Diagnoses in focus were mesothelioma (C45), asbestosis, and pleural plaque (J61 and J92). Yearly rates of inpatients treated for mesothelioma, asbestosis, or pleural plaque that were higher than the Croatian average (2.1) were recorded in the Counties of Split-Dalmatia (5.0), Dubrovnik-Neretva (3.9), Istria (3.7), and Primorje-Gorski kotar (3.1 per 100,000 people). From 2002 to 2007, 649 occupational diseases were reported, out of which 11.7% were asbestos-related. The most frequent were pleural plaque with asbestosis (38 cases, 50.0%), pleural plaque (23 cases, 30.3%), and mesothelioma (6 cases, 7.9%). Mortality attributable to asbestos was assessed using official Croatian National Statistics Bureau reports for 2002 to 2007 at the county and national level. During that period, Croatia recorded 312 deaths with the average yearly rate of 1.2 per 100.000 people. Four counties had higher rates than the national average: Primorje-Gorski kotar (3.4), Split-Dalmatia (2.8), Istria (2.8), and S1. Brod-Posavina (1.5). The number of inpatients treated for asbestos-related diseases was higher than the national average in the counties of Split-Dalmatia, Dubrovnik-Neretva, and Primorje-Gorski Kotar. Mesothelioma incidence was above the national average in the counties of Split-Dalmatia, Primorje-Gorski Kotar, and Istria. The rates of occupational, asbestos-related diseases were higher than the national average in the counties of Split-Dalmatia and Primorje-Gorski Kotar. We were aware that the interpretation of data is somewhat limited by the relatively small absolute number of treated persons and deaths for the observed period, by the fact that crude rates have not been adjusted for total numbers and for regional differences in population distribution by age and gender. The real extent of asbestos-related burden in Croatian general population remains unknown, because only occupational exposure has been monitored. Therefore, the National Public Health Institute and county public health institutes should implement a specific monitoring programme in collaboration with government environmental bodies to assess asbestos exposure of the population living in the vicinity of asbestos plants. It is also necessary to establish the number of exposed persons who have developed an asbestos-related disease. Their health should be monitored and their environment inspected on a regular basis.}, } @article {pmid20853774, year = {2009}, author = {Sarić, M}, title = {[Expectations after ban on asbestos].}, journal = {Arhiv za higijenu rada i toksikologiju}, volume = {60 Suppl}, number = {}, pages = {15-21}, pmid = {20853774}, issn = {0004-1254}, mesh = {Asbestos/*adverse effects ; Asbestosis/*epidemiology/prevention & control ; Croatia/epidemiology ; Environmental Exposure/*legislation & jurisprudence ; Female ; Humans ; Male ; Mesothelioma/epidemiology/etiology/prevention & control ; Occupational Exposure/*legislation & jurisprudence ; }, abstract = {This article brings a brief review of asbestos exposure and asbestos-related diseases in Croatia in view of the asbestos ban. The first cases of asbestosis were diagnosed in workers from an asbestos-cement factory in 1961. Between 1990 and 2007, 403 cases of asbestosis had been registered as occupational disease: 300 with parenchymal fibrosis and the rest with parenchymal and pleural changes, or pleural plaques. As a rule, asbestos-related changes were diagnosed at an early stage thanks to regular checkups of the exposed workers. Pleural plaques, considered to be the consequence of asbestos exposure, were also occasionally found in subjects who lived in areas with asbestos processing plants, but were not occupationally exposed. Early epidemiological studies on respiratory and gastrointestinal tract tumours in areas with an asbestos processing plant (1994) and an asbestos-cement plant (1995, 1996) focused on the occurrence of malignant tumours in persons exposed to asbestos at work or in the environment. More recently, the focus has shifted to the malignant pleural mesotelioma (MPM). An epidemiological study published in 2002 showed that the MPM incidence was significantly higher in the coastal area than in the rest of the country. About two thirds of patients with the tumour were occupationally exposed to asbestos. This uneven distribution of the tumour incidence is obviously related to shipbuilding and other industrial sources of asbestos exposure located in the coastal Croatia. Sources of environmental exposure to asbestos also have to be taken into account. The second part of this article ventures into the issues ahead of us, after asbestos has been banned in the country. The long latency period of cancers, and particularly of asbestos-related mesothelioma, implies that the incidence of this tumour will not drop over the next few decades. In Croatia, the average annual rate of MPM between 1991 and 2006 was 40, and ranged between 20 in 1991 to 61 in 1999. In 2006 it was 58. Age-standardised incidence of this tumour between 1991 and 1997 was 0.74 per 100,000 (1.34 per 100,000 for men and 0.27 per 100,000 for women). Sadly, the diagnosis of mesothelioma is seldom timely, and treatment is usually unsuccessful.}, } @article {pmid20853771, year = {2009}, author = {Cvitanović, S and Macan, J}, title = {Asbestos and asbestos-related diseases.}, journal = {Arhiv za higijenu rada i toksikologiju}, volume = {60 Suppl}, number = {}, pages = {1-2}, pmid = {20853771}, issn = {0004-1254}, mesh = {*Asbestosis/epidemiology/prevention & control ; Croatia ; Environmental Exposure/legislation & jurisprudence ; Humans ; Mesothelioma/epidemiology/*etiology/prevention & control ; Occupational Exposure/legislation & jurisprudence ; Pleural Neoplasms/epidemiology/*etiology/prevention & control ; }, } @article {pmid20852345, year = {2010}, author = {Fazzo, L and Nicita, C and Cernigliaro, A and Zona, A and Bruno, C and Fiumanò, G and Villari, C and Puglisi, G and Marinaccio, A and Comba, P and Tumino, R}, title = {[Mortality from asbestos-related causes and incidence of pleural mesothelioma among former asbestos cement workers in San Filippo del Mela (Sicily)].}, journal = {Epidemiologia e prevenzione}, volume = {34}, number = {3}, pages = {87-92}, pmid = {20852345}, issn = {1120-9763}, mesh = {Asbestos/*adverse effects/analysis ; Asbestosis/*epidemiology/etiology/mortality ; Female ; Humans ; Incidence ; Lung Neoplasms/epidemiology/etiology/mortality ; Male ; Mesothelioma/*epidemiology/etiology/mortality ; Occupational Exposure/*adverse effects/analysis ; Pleural Neoplasms/*epidemiology/etiology/mortality ; Sicily/epidemiology ; }, abstract = {OBJECTIVES: The present paper estimates the burden of asbestos-related disease among asbestos-cement production workers of the Sacelit plant that operated in San Filippo del Mela (Province of Messina) from 1958 through 1993.

SETTING AND PARTICIPANTS: The cohort was enumerated by the local committee of formerly exposed workers, with whom a collaboration was set up. The cohort includes 198 subjects with complete individual anagraphic information, out of 231 previous workers identified by the committee. A record-linkage with the Sicilian centre of the National mesothelioma registry enabled estimation of mesothelioma incidence for the years 1998-2008. Standardised proportionate mortality (SPMR) for asbestos-related causes was computed for the years 1986-2009. Sicilian Region constituted the reference population. The rationale for using SPMR rather than standardized mortality ratio (SMR) was a consequence for the lack of company files from which to obtain dates of start and termination of employment, and thus to compute person-years of observation, following the guidelines of the international scientific literature.

RESULTS: Standardised incidence ratio (SIR) for mesothelioma in the overall cohort was 251 (4 observed, 0.02 expected). Proportionate mortality analysis among male subjects showed significant increases for pneumoconiosis (SPMR 80.1, 5 observed), lung cancer (SPMR 2.81, 10 observed) and pleural neoplasms (SPMR 19.4, 2 observed).

CONCLUSIONS: Notwithstanding limitations in cohort reconstruction, for which the proportion of eligible subjects was 87.5% of those detected by the local committee, and the lack of information on duration of employment, it was possible to estimate a significant increase of the incidence of pleural mesothelioma with respect to Sicilian population. Also mortality from asbestos-related causes was in excess with respect to the regional reference population.}, } @article {pmid20850297, year = {2011}, author = {Robinson, C and Walsh, A and Larma, I and O'Halloran, S and Nowak, AK and Lake, RA}, title = {MexTAg mice exposed to asbestos develop cancer that faithfully replicates key features of the pathogenesis of human mesothelioma.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {47}, number = {1}, pages = {151-161}, doi = {10.1016/j.ejca.2010.08.015}, pmid = {20850297}, issn = {1879-0852}, mesh = {Animals ; Antineoplastic Agents/therapeutic use ; Asbestos/*toxicity ; Contactin 2/*metabolism ; Cyclooxygenase 2 Inhibitors/therapeutic use ; *Disease Models, Animal ; Female ; Irritants/toxicity ; Male ; Mesothelioma/drug therapy/*etiology ; Mice ; Mice, Transgenic ; Peritoneal Neoplasms/drug therapy/*etiology ; Thioglycolates/toxicity ; }, abstract = {Animal models provide an important tool for investigating the biology of cancer and for testing the efficacy of novel treatments. Here we describe several aspects of the transgenic MexTAg mouse that develops asbestos-induced mesothelioma. Targeted expression of the TAg transgene causes mesothelioma to develop more rapidly after asbestos exposure in wild-type mice with 100% incidence compared to 30% incidence in wild-type mice. MexTAg mice do not develop spontaneous mesothelioma and exhibit a very low incidence of other tumours. Here we show that TAg does not affect the aggressiveness or rate of progression of the mesotheliomas, suggesting that the oncogene alters only the rate at which disease is initiated. The instillation of an alternative inflammatory agent, thioglycollate, did not induce mesotheliomas, demonstrating acute inflammation is not sufficient for tumour development in MexTAg mice. We found that neither the age of a mouse at the time of exposure nor its gender were prognostic factors. MexTAg mice with mesotheliomas respond to treatment with a cytotoxic drug in a similar way to that of patients with mesothelioma, demonstrating the validity of the model. We also show that long-term treatment with a COX-2 inhibitor prior to the development of disease does not have a survival benefit, suggesting that this is not a useful cancer prevention therapy for asbestos-exposed individuals. The model is robust and suitable for testing a wide variety of protocols and a range of translational studies.}, } @article {pmid20849352, year = {2010}, author = {Maeda, M and Nishimura, Y and Kumagai, N and Hayashi, H and Hatayama, T and Katoh, M and Miyahara, N and Yamamoto, S and Hirastuka, J and Otsuki, T}, title = {Dysregulation of the immune system caused by silica and asbestos.}, journal = {Journal of immunotoxicology}, volume = {7}, number = {4}, pages = {268-278}, doi = {10.3109/1547691X.2010.512579}, pmid = {20849352}, issn = {1547-6901}, mesh = {Animals ; Asbestos/adverse effects/*immunology ; Autoimmunity ; Humans ; *Immune System/metabolism ; Immunologic Surveillance ; Immunomodulation ; Lung Neoplasms/chemically induced/*immunology/pathology ; Mesothelioma/chemically induced/*immunology/pathology ; Pneumoconiosis/*immunology/physiopathology ; Silicon Dioxide/adverse effects/*immunology ; }, abstract = {Silica and asbestos cause pneumoconioses known as silicosis and asbestosis, respectively, that are each characterized by progressive pulmonary fibrosis. While local effects of inhaled silica particles alter the function of alveolar macrophages and sequential cellular and molecular biological events, general systemic immunological effects may also evolve. One well-known health outcome associated with silica exposure/silicosis is an increase in the incidence of autoimmune disorders. In addition, while exposure to silica--in the crystalline form--has also been seen to be associated with the development of lung cancers, it remains unclear as to whether or not silicosis is a necessary condition for the elevation of silica-associated lung cancer risks. Since asbestos is a mineral silicate, it would be expected to also possess generalized immunotoxicological effects similar to those associated with silica particles. However, asbestos-exposed patients are far better known than silicotic patients for development of malignant diseases such as lung cancer and mesothelioma, and less so for the development of autoimmune disorders. With both asbestos and crystalline silica, one important dysregulatory outcome that needs to be considered is an alteration in tumor immunity that allows for silica- or asbestos- (or asbestos-associated agent)-induced tumors to survive and thrive in situ. In this review, the immunotoxicological effects of both silica and asbestos are presented and contrasted in terms of their abilities to induce immune system dysregulation that then are manifest by the onset of autoimmunity or by alterations in host-tumor immunity.}, } @article {pmid20849338, year = {2010}, author = {Lotti, M and Bergamo, L and Murer, B}, title = {Occupational toxicology of asbestos-related malignancies.}, journal = {Clinical toxicology (Philadelphia, Pa.)}, volume = {48}, number = {6}, pages = {485-496}, doi = {10.3109/15563650.2010.506876}, pmid = {20849338}, issn = {1556-9519}, mesh = {Asbestos/*toxicity ; Biomarkers, Tumor ; Humans ; Lung Neoplasms/*chemically induced/diagnosis/pathology ; Mesothelioma/*chemically induced/diagnosis/pathology ; Occupational Exposure/*adverse effects ; Tomography, X-Ray Computed ; }, abstract = {INTRODUCTION: Asbestos is banned in most Western countries but related malignancies are still of clinical concern because of their long latencies. This review identifies and addresses some controversial occupational and clinical aspects of asbestos-related malignancies.

METHODS: Papers published in English from 1980 to 2009 were retrieved from PubMed. A total of 307 original articles were identified and 159 were included.

ASSESSMENT OF EXPOSURE: The retrospective assessment of exposure is usually performed by using questionnaires and job exposure matrices and by careful collection of medical history. In this way crucial information about manufacturing processes and specific jobs can be obtained. In addition, fibers and asbestos bodies are counted in lung tissue, broncho-alveolar lavage, and sputum, but different techniques and interlaboratory variability hamper the interpretation of reported measurements. SCREENING FOR MALIGNANCIES: The effectiveness of low-dose chest CT screening in exposed workers is debatable. Several biomarkers have also been considered to screen individuals at risk for lung cancer and mesothelioma but reliable signatures are still missing. ATTRIBUTION OF LUNG CANCER: Exposures correlating with lung cancer are high and in the same range where asbestosis occurs. However, the unresolved question is whether the presence of fibrosis is a requirement for the attribution of lung cancer to asbestos. The etiology of lung cancer is difficult to define in cases of low-level asbestos exposure and concurrent smoking habits. MESOTHELIOMA: The diagnosis of malignant mesothelioma may also be difficult, because of procedures in sampling, fixation, and processing, and uses of immunohistochemical probes.

CONCLUSIONS: Assessment of exposure is crucial and requires accurate medical and occupational histories. Quantitative analysis of asbestos body burden is better performed in digested lung tissues by counting asbestos bodies by light microscopy and/or uncoated fibers by transmission electron microscopy. The benefits of screenings for asbestos-related malignancies are equivocal. The attribution of lung cancer to asbestos exposure is difficult in a clinical setting because of the need to assess asbestos body burden and the fact that virtually all these patients are also tobacco smokers or former smokers. Given the premise that asbestosis is necessary to causally link lung cancer to asbestos, it follows that the assessment of both lung fibrosis and asbestos body burden is necessary.}, } @article {pmid20846704, year = {2011}, author = {Bollo, E and Scaglione, FE and Tursi, M and Schröder, C and Degiorgi, G and Belluso, E and Capella, S and Bellis, D}, title = {Malignant pleural mesothelioma in a female lion (Panthera leo).}, journal = {Research in veterinary science}, volume = {91}, number = {1}, pages = {116-118}, doi = {10.1016/j.rvsc.2010.08.005}, pmid = {20846704}, issn = {1532-2661}, mesh = {Animal Diseases/pathology ; Animals ; *Animals, Zoo ; Female ; *Lions ; Mesothelioma/pathology/*veterinary ; Pleural Neoplasms/pathology/*veterinary ; }, abstract = {An 18-year-old female lion (Panthera leo) was referred to the Department of Animal Pathology of the University of Turin (Italy). At necropsy, multiple nodular, 4-20-mm, confluent white firm nodules were scattered throughout the pleural surfaces of the thoracic wall and of the lungs. Histological lesions were represented by proliferations of papillary structures lined by cuboidal basophilic mesothelial cells with large, oval nuclei and abundant granular eosinophilic cytoplasm. Immunohistochemistry revealed immunoreactivity for pancytokeratin and vimentin. None of the cells expressed calretinin antigen. Asbestos fibers and asbestos bodies were not detected respectively by light microscopy and by Scanning Electron Microscope-Energy Dispersive Spectrometer investigations. On the contrary, chrysotile asbestos were identified in samples from shelter material. Histological and immunohistochemical findings were consistent with the diagnosis of an epithelial malignant mesothelioma. To our best knowledge, this is the first report of a pleural mesothelioma in a lion.}, } @article {pmid20833490, year = {2011}, author = {Sharma, H and Bell, I and Schofield, J and Bird, G}, title = {Primary peritoneal mesothelioma: case series and literature review.}, journal = {Clinics and research in hepatology and gastroenterology}, volume = {35}, number = {1}, pages = {55-59}, doi = {10.1016/j.gcb.2010.07.016}, pmid = {20833490}, issn = {2210-741X}, mesh = {Aged ; Fatal Outcome ; Female ; Humans ; Male ; *Mesothelioma/diagnosis/therapy ; Middle Aged ; *Peritoneal Neoplasms/diagnosis/therapy ; }, abstract = {Primary peritoneal mesothelioma is a rare and aggressive tumour. We present six consecutive cases treated by our institution in the last three years. All were between 56-65 years old and only one gave a history of direct contact with asbestos. Four of the patients showed a thrombocytosis on presentation but other blood tests and evaluation of ascitic fluid were normal. In all cases, the diagnosis was made through investigation of mixed abdominal symptoms with CT scanning and laparoscopic biopsy. Despite the use of modern chemotherapy, response to treatment was unpredictable, with survival from ten weeks to three years.}, } @article {pmid20831825, year = {2010}, author = {Hillegass, JM and Shukla, A and MacPherson, MB and Lathrop, SA and Alexeeva, V and Perkins, TN and van der Vliet, A and Vacek, PM and Gunter, ME and Mossman, BT}, title = {Mechanisms of oxidative stress and alterations in gene expression by Libby six-mix in human mesothelial cells.}, journal = {Particle and fibre toxicology}, volume = {7}, number = {}, pages = {26}, pmid = {20831825}, issn = {1743-8977}, support = {R01 HL085646/HL/NHLBI NIH HHS/United States ; T32ES007122/ES/NIEHS NIH HHS/United States ; }, mesh = {Asbestos, Amphibole/*toxicity ; Asbestos, Crocidolite/toxicity ; Cells, Cultured ; Epithelial Cells/*drug effects/metabolism ; Gene Expression/drug effects ; Glutathione/metabolism ; Heme Oxygenase-1/genetics ; Humans ; Oxidative Stress/*drug effects ; Reactive Oxygen Species/metabolism ; Superoxide Dismutase/analysis ; }, abstract = {BACKGROUND: Exposures to an amphibole fiber in Libby, Montana cause increases in malignant mesothelioma (MM), a tumor of the pleural and peritoneal cavities with a poor prognosis. Affymetrix microarray/GeneSifter analysis was used to determine alterations in gene expression of a human mesothelial cell line (LP9/TERT-1) by a non-toxic concentration (15×10(6) μm2/cm2) of unprocessed Libby six-mix and negative (glass beads) and positive (crocidolite asbestos) controls. Because manganese superoxide dismutase (MnSOD; SOD2) was the only gene upregulated significantly (p < 0.05) at both 8 and 24 h, we measured SOD protein and activity, oxidative stress and glutathione (GSH) levels to better understand oxidative events after exposure to non-toxic (15×10(6) μm2/cm2) and toxic concentrations (75×10(6) μm2/cm2) of Libby six-mix.

RESULTS: Exposure to 15×10(6) μm2/cm2 Libby six-mix elicited significant (p < 0.05) upregulation of one gene (SOD2; 4-fold) at 8 h and 111 gene changes at 24 h, including a 5-fold increase in SOD2. Increased levels of SOD2 mRNA at 24 h were also confirmed in HKNM-2 normal human pleural mesothelial cells by qRT-PCR. SOD2 protein levels were increased at toxic concentrations (75×10(6) μm2/cm2) of Libby six-mix at 24 h. In addition, levels of copper-zinc superoxide dismutase (Cu/ZnSOD; SOD1) protein were increased at 24 h in all mineral groups. A dose-related increase in SOD2 activity was observed, although total SOD activity remained unchanged. Dichlorodihydrofluorescein diacetate (DCFDA) fluorescence staining and flow cytometry revealed a dose- and time-dependent increase in reactive oxygen species (ROS) production by LP9/TERT-1 cells exposed to Libby six-mix. Both Libby six-mix and crocidolite asbestos at 75×10(6) μm2/cm2 caused transient decreases (p < 0.05) in GSH for up to 24 h and increases in gene expression of heme oxygenase 1 (HO-1) in LP9/TERT-1 and HKNM-2 cells.

CONCLUSIONS: Libby six-mix causes multiple gene expression changes in LP9/TERT-1 human mesothelial cells, as well as increases in SOD2, increased production of oxidants, and transient decreases in intracellular GSH. These events are not observed at equal surface area concentrations of nontoxic glass beads. Results support a mechanistic basis for the importance of SOD2 in proliferation and apoptosis of mesothelial cells and its potential use as a biomarker of early responses to mesotheliomagenic minerals.}, } @article {pmid20821038, year = {2010}, author = {Lacourt, A and Rolland, P and Gramond, C and Astoul, P and Chamming's, S and Ducamp, S and Frenay, C and Galateau-Sallé, F and Gilg Soit Ilg, A and Imbernon, E and Le Stang, N and Pairon, JC and Goldberg, M and Iwatsubo, Y and Salmi, LR and Brochard, P}, title = {Attributable risk in men in two French case-control studies on mesothelioma and asbestos.}, journal = {European journal of epidemiology}, volume = {25}, number = {11}, pages = {799-806}, pmid = {20821038}, issn = {1573-7284}, mesh = {Aged ; Asbestos/*adverse effects ; Case-Control Studies ; Female ; France/epidemiology ; Humans ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Exposure/adverse effects ; Patient Selection ; Risk Assessment/standards ; Selection Bias ; }, abstract = {Pleural mesothelioma is a primary tumor of the pleura that is mainly due to asbestos exposure. To study the relationship between mesothelioma and occupational asbestos exposure in France, two case-control studies (A and B) were conducted. A substantial difference in the attributable risk in the population (AR(p)) was observed among men: 44.5% (95% CI: [32.6-56.4]) in study A and 83.2% (95% CI: [76.8-89.6]) in study B. As different exposure assessment expert methods were used, the main objective of this work was to re-estimate the AR(p) men in two case-control studies according to a common standardized exposure assessment by using a Job Exposure Matrix (JEM) and to assess the role of subjects' selection. The initial observed AR(p) difference was maintained: 36.3% (95% CI: [24.3-50.3]) in study A and 69.7% (95% CI: [51.7-83.2]) in study B. Further investigations highlighted the potential selection bias introduced in both studies, especially among controls. The AR(p) could be underestimated in study A and overestimated in study B. After weighting subjects according to distribution of socio-economic status in the general population for controls and according to distribution of socio-economic status of cases registered by the French National Mesothelioma Surveillance Program, re-estimated AR(p) values were 52.4% in study A and 70.2% in study B. These results provide additional information to describe the relationship between pleural mesothelioma and occupational asbestos exposure, but also confirm the importance of subjects' recruitment in case control studies, particularly control selection.}, } @article {pmid20815094, year = {2010}, author = {Creaney, J and Musk, AW and Robinson, BW}, title = {Sensitivity of urinary mesothelin in patients with malignant mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {5}, number = {9}, pages = {1461-1466}, doi = {10.1097/jto.0b013e3181e392d7}, pmid = {20815094}, issn = {1556-1380}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Asbestosis/blood/urine ; Biomarkers, Tumor/metabolism/*urine ; Case-Control Studies ; Creatinine/urine ; Female ; GPI-Linked Proteins/blood/urine ; Glomerular Filtration Rate ; Humans ; Idiopathic Pulmonary Fibrosis/blood/chemically induced/urine ; Immunoblotting ; Male ; Membrane Glycoproteins/blood/*urine ; Mesothelin ; Mesothelioma/blood/drug therapy/*urine ; Middle Aged ; Pleural Neoplasms/blood/drug therapy/*urine ; Prognosis ; ROC Curve ; Sarcoidosis, Pulmonary/blood/chemically induced/urine ; Sensitivity and Specificity ; Survival Rate ; Young Adult ; }, abstract = {INTRODUCTION: Malignant mesothelioma (MM) is an aggressive, uniformly fatal tumor usually caused by exposure to asbestos. Soluble mesothelin has been intensively investigated in the serum as a biomarker for this disease. As urine is less complex and less invasive to collect than serum and may be a more acceptable specimen for large-scale screening studies of asbestos-exposed individuals, we determined whether the sensitivity and specificity for MM could be improved by measuring soluble mesothelin in the urine.

METHODS: Soluble mesothelin concentrations were determined using the MESOMARK assay in concurrent serum and urine samples from 70 patients with pleural MM, 111 patients with asbestos-related lung or pleural disease, and 45 patients with benign nonasbestos-related lung and pleural disease. Only patients with serum creatinine levels within the normal range were included in the study. Sensitivities were determined and receiver operator characteristic curves were generated to compare the diagnostic accuracy of mesothelin in the serum and urine.

RESULTS: At a specificity of 95% relative to individuals with benign lung or pleural disease, serum mesothelin had a sensitivity of 66% and area under the curve of 0.882, whereas urinary mesothelin corrected for urine creatinine concentration had a sensitivity of 53% and area under the curve of 0.787.

CONCLUSIONS: The sensitivity of urinary mesothelin does not warrant the use of urine as a biomarker specimen for MM diagnosis.}, } @article {pmid20812661, year = {2010}, author = {Barbieri, PG and Somigliana, A and Tironi, A}, title = {[Lung asbestos fibre burden in textile workers with malignant mesothelioma].}, journal = {La Medicina del lavoro}, volume = {101}, number = {3}, pages = {199-206}, pmid = {20812661}, issn = {0025-7818}, mesh = {Aged ; Aged, 80 and over ; Asbestos, Amphibole/*analysis ; Female ; Humans ; Lung/*chemistry ; Lung Neoplasms/*chemistry ; Male ; Mesothelioma/*chemistry ; Middle Aged ; Mineral Fibers/*analysis ; Occupational Diseases ; *Textile Industry ; }, abstract = {BACKGROUND: Lung burden of amphibole fibres is a good biological index of occupational cumulative asbestos exposure. Malignant mesothelioma (MM) has been amply documented in textile industry workers, dealing either with mineral fibres or with vegetable and animal fibres. So far the concentration of asbestos fibres in lung tissue among textile workers has not been reported in Italy. We analysed asbestos burden in the lung tissue of eleven textile-workers with malignant mesothelioma, mainly employed in industries near Brescia, in the North of Italy.

OBJECTIVES: To characterize lung asbestos concentration and fibre type retained in the lung of asbestos and non-asbestos textile workers.

METHODS: Sample of lung parenchyma from necropsies and extrapleural pneumonectomy were collected, stored and analysed by scanning electron microscope, according to the methods recommended in the current scientific literature. Nine patients were interviewed directly for occupational history.

RESULTS: Eleven cases of MM (10 primary pleural, 1 primary peritoneal) were collected, 9 women and 2 men, aged between 51 and 87 years, 4 asbestos-textile workers and 7 non-asbestos textile workers. The highest values of asbestos fibres were detected in all the workers of the former group and in 3 non-asbestos workers (jute recycling employees), with concentrations between 9.1 and 397 million/g of dried lung tissue. The total fibre concentration in the other 4 non-asbestos textile workers (silk and cotton production workers) ranged from 0.33 to 1.2 million/g of dried lung tissue. In only one of these subjects, did lung amphibole burden exceed 1,000,000 amphibole fibres longer than 1 microm per g of dried tissue. Eight cases out of eleven, showed a higher concentration of amphiboles than chrysotile. We detected amphibole fibres in all the "non-asbestos" textile workers and for two of them a higher concentration of tremolite.

CONCLUSION: i) Among textile workers using asbestos or jute recycling, the asbestos fibre burden is as high as that found in other high risk jobs (e.g. asbestos-cement workers); ii) among non-asbestos textile workers, employed in cotton and silk production, the fibre content in lung tissue was much lower and it was nonetheless above the occupational cut-off for one of them; iii) tremolite found in lung tissue of non-asbestos textile workers with MM could be a contaminant of chrysotile friction materials or originate, with other amphiboles, from some other source as yet to be investigated.}, } @article {pmid20799022, year = {2010}, author = {Makidono, A and Matsusako, M and Oikado, K and Saida, Y and Otsuji, M and Otawa, M and Suzuki, K and Inai, K and Ishikawa, S}, title = {Malignant pleural mesothelioma detected by spontaneous pneumothorax.}, journal = {Japanese journal of radiology}, volume = {28}, number = {7}, pages = {547-551}, pmid = {20799022}, issn = {1867-108X}, mesh = {Adult ; Biopsy ; Combined Modality Therapy ; Diagnosis, Differential ; Humans ; Magnetic Resonance Imaging ; Male ; Mesothelioma/*diagnosis/radiotherapy/surgery ; Neoplasm Recurrence, Local ; Pleural Neoplasms/*diagnosis/radiotherapy/surgery ; Pneumonectomy ; Pneumothorax/*diagnosis/surgery ; Tomography, X-Ray Computed ; }, abstract = {We report a middle-aged man, without occupational or environmental exposure to asbestos, who presented with spontaneous pneumothorax. Computed tomography showed a 13-mm right apical mass. He underwent tumorectomy and was diagnosed with malignant pleural mesothelioma. A local recurrence with multiple and diffuse pleural involvement later appeared. The patient eventually underwent panpleuropneumonectomy, recovered well, and has been doing well for 18 months.}, } @article {pmid20798014, year = {2010}, author = {Marinaccio, A and Binazzi, A and Di Marzio, D and Scarselli, A and Verardo, M and Mirabelli, D and Gennaro, V and Mensi, C and Merler, E and De Zotti, R and Mangone, L and Chellini, E and Pascucci, C and Ascoli, V and Menegozzo, S and Cavone, D and Cauzillo, G and Nicita, C and Melis, M and Iavicoli, S}, title = {Incidence of extrapleural malignant mesothelioma and asbestos exposure, from the Italian national register.}, journal = {Occupational and environmental medicine}, volume = {67}, number = {11}, pages = {760-765}, doi = {10.1136/oem.2009.051466}, pmid = {20798014}, issn = {1470-7926}, mesh = {Adolescent ; Adult ; Age Distribution ; Aged ; Asbestos/*toxicity ; Child ; Child, Preschool ; Environmental Exposure/adverse effects/analysis ; Epidemiologic Methods ; Female ; Heart Neoplasms/diagnosis/epidemiology/etiology ; Humans ; Infant ; Infant, Newborn ; Italy/epidemiology ; Male ; Mesothelioma/diagnosis/epidemiology/*etiology ; Middle Aged ; Occupational Diseases/diagnosis/epidemiology/etiology ; Pericardium ; Peritoneal Neoplasms/diagnosis/epidemiology/etiology ; Pleural Neoplasms/diagnosis/epidemiology/etiology ; Sex Distribution ; Young Adult ; }, abstract = {OBJECTIVES: The epidemiology of extrapleural malignant mesothelioma is rarely discussed and the risk of misdiagnosis and the very low incidence complicate the picture. This study presents data on extrapleural malignant mesothelioma from the Italian National Mesothelioma Register (ReNaM).

METHODS: ReNaM works on a regional basis, searching for cases and interviewing subjects to investigate asbestos exposure. Classification and code criteria for certainty of diagnosis and exposure modalities are set by national guidelines. Between 1993 and 2004, 681 cases were collected. Incidence measures and exposure data refer to the ReNaM database. Age-standardised rates were estimated by the direct method using the Italian resident population in 2001. Correlations between the incidence of pleural and non-pleural malignant mesothelioma for the 103 Italian provinces were analysed.

RESULTS: Standardised incidence rates (Italy, 2004, per million inhabitants) were 2.1 and 1.2 cases for the peritoneal site (in men and women, respectively), 0.2 cases for the tunica vaginalis testis, and 0.1 in the pericardial site, varying widely in different parts of the country. Mean age at diagnosis for all extrapleural malignant mesothelioma cases was 64.4 years and the men/women ratio was 1.57:1. Median latency was over 40 years for all extrapleural sites combined. The correlation between pleural and peritoneal mesothelioma was 0.71 (Pearson's r coefficient, p<0.001). Modalities of exposure to asbestos fibres were investigated for 392 cases.

CONCLUSIONS: The rarity of the disease, the low specificity of diagnosis and difficulties in identifying the modalities of asbestos exposure call for caution in discussing aetiological factors other than asbestos.}, } @article {pmid20737138, year = {2011}, author = {Gube, M and Taeger, D and Weber, DG and Pesch, B and Brand, P and Johnen, G and Müller-Lux, A and Gross, IM and Wiethege, T and Weber, A and Raithel, HJ and Kraus, T and Brüning, T}, title = {Performance of biomarkers SMRP, CA125, and CYFRA 21-1 as potential tumor markers for malignant mesothelioma and lung cancer in a cohort of workers formerly exposed to asbestos.}, journal = {Archives of toxicology}, volume = {85}, number = {3}, pages = {185-192}, doi = {10.1007/s00204-010-0580-2}, pmid = {20737138}, issn = {1432-0738}, mesh = {Aged ; Antigens, Neoplasm/blood ; Asbestos/*adverse effects ; Biomarkers, Tumor/*blood ; CA-125 Antigen/blood ; Cohort Studies ; Female ; GPI-Linked Proteins/blood ; Humans ; Keratin-19/blood ; Lung Neoplasms/*diagnosis/mortality/pathology ; Male ; Mesothelin ; Mesothelioma/*diagnosis/mortality/pathology ; Middle Aged ; Pleural Neoplasms/*diagnosis/mortality/pathology ; Predictive Value of Tests ; Prospective Studies ; Sensitivity and Specificity ; }, abstract = {The aim of the study is to examine the cancer-predictive values of SMRP (soluble mesothelin-related peptides), CA125, and CYFRA21-1 as potential tumor markers for lung cancer and malignant mesothelioma in a cohort of workers formerly exposed to asbestos. A voluntary surveillance program has been established for German workers with former asbestos exposure. A subgroup of 626 subjects with a mean age of 63 years (range 53-70 years) at baseline was enrolled in an extended health examination program with high-resolution computer tomography (HRCT) of the chest and blood drawing between 1993 and 1997. Serum concentrations of SMRP, CA125, and CYFRA21-1 were measured in archived serum samples in 2005 and 2006. A mortality follow-up was conducted through 2007. So far, 12 cases with lung cancer and 20 cases with malignant mesothelioma have been observed in this cohort. The average time between sample collection and diagnosis was 4.7 years. Analyzed biomarkers showed low sensitivities (5-25%) and positive predictive values (4-30%) for both cancer sites. Marker combinations resulted in sensitivities between 5 and 50% and positive predictive values ranging from 3 to 14%. Even in those cases, where biomarker concentrations were available within 36 months before diagnosis, no trend for increasing biomarker levels was observed. The analyzed tumor markers were characterized by high specificities, but low sensitivities. SMRP, CA125, and CYFRA21-1 alone or in combination were less suitable to serve as predictors for the diagnosis of lung cancer or malignant mesothelioma. However, a prospective study with annual sampling might reveal a better predictive value of these markers.}, } @article {pmid20732523, year = {2010}, author = {Wolf, AS and Richards, WG and Tilleman, TR and Chirieac, L and Hurwitz, S and Bueno, R and Sugarbaker, DJ}, title = {Characteristics of malignant pleural mesothelioma in women.}, journal = {The Annals of thoracic surgery}, volume = {90}, number = {3}, pages = {949-56; discussion 956}, doi = {10.1016/j.athoracsur.2010.04.110}, pmid = {20732523}, issn = {1552-6259}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Mesothelioma/*mortality ; Middle Aged ; Pleural Neoplasms/*mortality ; Prognosis ; Retrospective Studies ; Sex Factors ; Survival Rate ; Young Adult ; }, abstract = {BACKGROUND: The incidence of malignant pleural mesothelioma (MPM) is higher in men than in women, likely due to increased occupational asbestos exposure among men. Women also appear to experience better long-term survival. This study evaluates the role of gender in relation to established prognostic factors in MPM.

METHODS: We reviewed 715 cases of MPM treated with extrapleural pneumonectomy at our institution between July 1987 and December 2008. Data for patients with epithelial and nonepithelial tumors were analyzed separately. Kaplan-Meier and Cox regression analyses were used to estimate survival for various cohorts to assess the relationship between gender and survival independent of age at surgery, stage, side, and preoperative laboratory studies.

RESULTS: Of the 702 patients with complete data available, 114 out of 450 patients with epithelial tumors and 31 out of 252 patients with nonepithelial histology were women. Women with epithelial (and not nonepithelial) disease were found to differ significantly from men with respect to younger age, higher rate of thrombocytosis, and longer survival after surgery. The effect of gender on survival of patients with epithelial disease persisted when controlling for age, stage, thrombocytosis, leukocytosis, and anemia with a multivariable analysis. No significant differences in survival were seen among patients with nonepithelial disease with regard to gender, age, or anemia.

CONCLUSIONS: In the absence of other negative prognostic factors, women with epithelial MPM demonstrated a survival advantage. These findings support an aggressive approach to treating MPM including extrapleural pneumonectomy in individuals with favorable prognostic predictors, particularly women with epithelial histology and no other risk factors.}, } @article {pmid20722572, year = {2010}, author = {Li, JY and Yong, TY and Kuss, BJ and Klebe, S and Kotasek, D and Barbara, JA}, title = {Malignant pleural mesothelioma with associated minimal change disease and acute renal failure.}, journal = {Renal failure}, volume = {32}, number = {8}, pages = {1012-1015}, doi = {10.3109/0886022X.2010.502275}, pmid = {20722572}, issn = {1525-6049}, mesh = {Acute Kidney Injury/*etiology/pathology/therapy ; Humans ; Male ; Mesothelioma/*complications/*pathology/therapy ; Middle Aged ; Nephrosis, Lipoid/etiology/pathology/therapy ; Pleural Neoplasms/*complications/*pathology/therapy ; }, abstract = {Paraneoplastic manifestations in malignant pleural mesothelioma are rare. We report a case of malignant pleural mesothelioma associated with minimal change disease (MCD). A 58-year-old man with occupational exposure to asbestos presented with severe peripheral edema, heavy proteinuria, and acute renal failure shortly after the diagnosis of mesothelioma had been confirmed. The renal biopsy demonstrated MCD. The underlying pathogenesis of this association remains unknown.}, } @article {pmid20721899, year = {2011}, author = {Egilman, D and Menéndez, LM}, title = {A case of occupational peritoneal mesothelioma from exposure to tremolite-free chrysotile in Quebec, Canada: A black swan case.}, journal = {American journal of industrial medicine}, volume = {54}, number = {2}, pages = {153-156}, doi = {10.1002/ajim.20882}, pmid = {20721899}, issn = {1097-0274}, mesh = {Aged ; Asbestos, Amphibole/toxicity ; Asbestos, Serpentine/*toxicity ; Fatal Outcome ; Humans ; Male ; Mesothelioma/*epidemiology/etiology ; Occupational Diseases/*epidemiology/etiology ; Occupational Exposure/*adverse effects/statistics & numerical data ; Peritoneal Neoplasms/*epidemiology/etiology ; Quebec/epidemiology ; }, abstract = {BACKGROUND: Tremolite contamination has been proposed as the cause of mesothelioma in workers exposed to commercial chrysotile. The asbestos industry and scientists it has sponsored, for example, have argued that commercial chrysotile does not cause peritoneal mesothelioma.

METHOD: Case report of peritoneal mesothelioma in a mill worker from a tremolite free Canadian mine.

RESULTS: Reports from pathology and occupational health and safety panels conclude that this mill worker developed work-related peritoneal mesothelioma.

CONCLUSION: Chrysotile without tremolite can cause peritoneal mesothelioma.}, } @article {pmid20716277, year = {2010}, author = {Hillegass, JM and Shukla, A and Lathrop, SA and MacPherson, MB and Beuschel, SL and Butnor, KJ and Testa, JR and Pass, HI and Carbone, M and Steele, C and Mossman, BT}, title = {Inflammation precedes the development of human malignant mesotheliomas in a SCID mouse xenograft model.}, journal = {Annals of the New York Academy of Sciences}, volume = {1203}, number = {}, pages = {7-14}, pmid = {20716277}, issn = {1749-6632}, support = {R01 CA106567-01A1/CA/NCI NIH HHS/United States ; T32 ES007122-30/ES/NIEHS NIH HHS/United States ; P01 CA114047-01A10002/CA/NCI NIH HHS/United States ; P01CA114047/CA/NCI NIH HHS/United States ; R01CA106567/CA/NCI NIH HHS/United States ; R01 CA106567/CA/NCI NIH HHS/United States ; T32ES007122/ES/NIEHS NIH HHS/United States ; T32 ES007122/ES/NIEHS NIH HHS/United States ; P01 CA114047/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Carcinoma/chemistry/metabolism/pathology ; Cell Line ; Cell Line, Tumor ; Cell Transformation, Neoplastic/chemistry/metabolism/*pathology ; Cytokines/biosynthesis/chemistry/physiology ; Disease Models, Animal ; Fibrosarcoma/chemistry/metabolism/pathology ; Humans ; Inflammation Mediators/chemistry/metabolism/*physiology ; Intercellular Signaling Peptides and Proteins/biosynthesis/chemistry/physiology ; Male ; Mesothelioma/chemistry/metabolism/*pathology ; Mice ; Mice, SCID ; Neutrophils/pathology ; Pleural Neoplasms/chemistry/metabolism/*pathology ; Protein Array Analysis ; Time Factors ; *Xenograft Model Antitumor Assays/methods ; }, abstract = {Asbestos fibers cause chronic inflammation that may be critical to the development of malignant mesothelioma (MM). Two human MM cell lines (Hmeso, PPM Mill) were used in a SCID mouse xenograft model to assess time-dependent patterns of inflammation and tumor formation. After intraperitoneal (IP) injection of MM cells, mice were euthanized at 7, 14, and 30 days, and peritoneal lavage fluid (PLF) was examined for immune cell profiles and human and mouse cytokines. Increases in human MM-derived IL-6, IL-8, bFGF, and VEGF were observed in mice at 7 days postinjection of either MM line, and a striking neutrophilia was observed at all time points. Free-floating tumor spheroids developed in mice at 14 days, and both spheroids and adherent MM tumor masses occurred in all mice at 30 days. Results suggest that inflammation and cytokine production precede and may be critical to the development of MMs.}, } @article {pmid20716011, year = {2010}, author = {Park, EK and Thomas, PS and Yates, DH}, title = {Biomarkers for early detection of mesothelioma in asbestos-exposed subjects.}, journal = {Clinical chemistry and laboratory medicine}, volume = {48}, number = {11}, pages = {1673-1674}, doi = {10.1515/CCLM.2010.306}, pmid = {20716011}, issn = {1437-4331}, mesh = {Asbestos/*adverse effects ; Biomarkers, Tumor/*analysis ; Early Detection of Cancer/*methods ; Environmental Exposure/*adverse effects ; Humans ; Male ; Mesothelioma/*chemically induced/*diagnosis ; Osteopontin/analysis ; }, } @article {pmid20705571, year = {2010}, author = {, }, title = {Asbestos is still with us: repeat call for a universal ban.}, journal = {Archives of environmental & occupational health}, volume = {65}, number = {3}, pages = {121-126}, doi = {10.1080/19338241003776104}, pmid = {20705571}, issn = {2154-4700}, mesh = {*Asbestos/adverse effects/supply & distribution ; Asbestosis/prevention & control ; Environmental Exposure/legislation & jurisprudence/prevention & control ; Humans ; International Cooperation/legislation & jurisprudence ; Mining/legislation & jurisprudence ; Occupational Exposure/*legislation & jurisprudence/prevention & control ; United Nations/legislation & jurisprudence ; }, abstract = {All forms of asbestos are proven human carcinogens. All forms of asbestos cause malignant mesothelioma, lung, laryngeal, and ovarian cancers, and may cause gastrointestinal and other cancers. No exposure to asbestos is without risk. Asbestos cancer victims die painful lingering deaths. These deaths are almost entirely preventable. When evidence of the carcinogenicity of asbestos became incontrovertible, concerned parties, including the Collegium Ramazzini, called for a universal ban on the mining, manufacture, and use of asbestos in all countries around the world (J Occup Environ Med. 1999;41:830-832). Asbestos is now banned in 52 countries, and safer products have replaced many materials that once were made with asbestos. Nonetheless, a large number of countries still use, import, and export asbestos and asbestos-containing products. And in many countries that have banned other forms of asbestos, the so-called "controlled use" of chrysotile asbestos is exempted from the ban, an exemption that has no basis in medical science but rather reflects the political and economic influence of the asbestos mining and manufacturing industry. All countries of the world have an obligation to their citizens to join in the international endeavor to ban all forms of asbestos. An international ban on asbestos is urgently needed.}, } @article {pmid20697183, year = {2010}, author = {Ngatu, NR and Suzuki, S and Kusaka, Y and Shida, H and Akira, M and Suganuma, N}, title = {Effect of a two-hour training on physicians' skill in interpreting Pneumoconiotic chest radiographs.}, journal = {Journal of occupational health}, volume = {52}, number = {5}, pages = {294-301}, doi = {10.1539/joh.l10065}, pmid = {20697183}, issn = {1348-9585}, mesh = {Asbestos/toxicity ; *Clinical Competence ; Dust ; *Education, Medical, Continuing ; Environmental Exposure ; Female ; Humans ; Japan ; Male ; Occupational Exposure ; Physicians/standards ; Pneumoconiosis/*diagnostic imaging ; Radiography, Thoracic ; }, abstract = {OBJECTIVE: Occupational lung diseases have specific radiographic manifestations not always well known by physicians. In Japan, asbestos-related diseases became a public health concern after the "Kubota Shock", when a number of workers and residents living nearby a manufacturer of asbestos-made ducts developed mesothelioma caused by asbestos exposure. This preliminary intervention trial evaluated the effect of two-hour training on inexperienced physicians' skill in interpreting pneumoconiotic chest radiographs.

METHODS: One hundred-two Japanese physicians participated in two reading-tests, using 12 radiographs, before and after the two-hour training with ILO/ICRP and Japan Pneumoconioses Study Group (JPSG) reading materials. Physicians had to check for the presence or absence of small opacity and pleural plaque consistent with pneumoconiosis. Sensitivity and specificity equal or greater than 70% were considered good, 50 to 69% acceptable and less than 50%, poor.

RESULTS: Post-training improvements in physicians' skills were seen. For small opacity, there was an increase in the proportion of physicians with good specificity, from 42% to 60%. For pleural plaque, the proportion of physicians with good specificity and good sensitivity increased, from 60% to 67% and from 18% to 25%, respectively. Also, significant improvements were observed in overall sensitivity for pleural plaque, from 46% to 60% (p<0.0001), and specificity for small opacity, from 65% to 73% (p<0.0001).

CONCLUSIONS: This study showed that two-hour participatory training may enhance physicians' skill in interpreting pneumoconiotic chest radiographs. There are countries without any pneumoconiosis screening program despite the WHO/ILO call for worldwide cooperation in eliminating it. Although the two-hour course cannot replace the five-day ILO workshop, such a program would be useful in areas with environmental or occupational exposure to dust.}, } @article {pmid20695727, year = {2010}, author = {Bernstein, DM and Rogers, RA and Sepulveda, R and Donaldson, K and Schuler, D and Gaering, S and Kunzendorf, P and Chevalier, J and Holm, SE}, title = {The pathological response and fate in the lung and pleura of chrysotile in combination with fine particles compared to amosite asbestos following short-term inhalation exposure: interim results.}, journal = {Inhalation toxicology}, volume = {22}, number = {11}, pages = {937-962}, doi = {10.3109/08958378.2010.497818}, pmid = {20695727}, issn = {1091-7691}, mesh = {Animals ; Asbestos, Amosite/*administration & dosage/metabolism/toxicity ; Asbestos, Serpentine/*administration & dosage/metabolism/toxicity ; Inhalation Exposure/*adverse effects ; Lung/drug effects/metabolism/*pathology ; Male ; Particulate Matter/*administration & dosage/toxicity ; Pilot Projects ; Pleura/drug effects/metabolism/*pathology ; Rats ; Time Factors ; }, abstract = {The pathological response and translocation of a commercial chrysotile product similar to that which was used through the mid-1970s in a joint compound intended for sealing the interface between adjacent wall boards was evaluated in comparison to amosite asbestos. This study was unique in that it presents a combined real-world exposure and was the first study to investigate whether there were differences between chrysotile and amosite asbestos fibers in time course, size distribution, and pathological response in the pleural cavity. Rats were exposed by inhalation 6 h/day for 5 days to either sanded joint compound consisting of both chrysotile fibers and sanded joint compound particles (CSP) or amosite asbestos. Subgroups were examined through 1-year postexposure. No pathological response was observed at any time point in the CSP-exposure group. The long chrysotile fibers (L > 20 microm) cleared rapidly (T(1/2) of 4.5 days) and were not observed in the pleural cavity. In contrast, a rapid inflammatory response occurred in the lung following exposure to amosite resulting in Wagner grade 4 interstitial fibrosis within 28 days. Long amosite fibers had a T(1/2) > 1000 days and were observed in the pleural cavity within 7 days postexposure. By 90 days the long amosite fibers were associated with a marked inflammatory response on the parietal pleural. This study provides support that CSP following inhalation would not initiate an inflammatory response in the lung, and that the chrysotile fibers present do not migrate to, or cause an inflammatory response in the pleural cavity, the site of mesothelioma formation.}, } @article {pmid20684436, year = {2010}, author = {Martines, V and Fioravanti, M and Anselmi, A and Attili, F and Battaglia, D and Cerratti, D and Ciarrocca, M and D'Amelio, R and De Lorenzo, G and Ferrante, E and Gaudioso, F and Mascia, E and Rauccio, A and Siena, S and Palitti, T and Tucci, L and Vacca, D and Vigliano, R and Zelano, V and Tomei, F and Sancini, A}, title = {[Algorithm for assessment of exposure to asbestos].}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {32}, number = {2}, pages = {154-161}, pmid = {20684436}, issn = {1592-7830}, mesh = {Algorithms ; Asbestos/*adverse effects ; Asbestosis/complications/*epidemiology/prevention & control ; Humans ; Italy/epidemiology ; Mesothelioma/*epidemiology/etiology/prevention & control ; Meta-Analysis as Topic ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*epidemiology/etiology/prevention & control ; Predictive Value of Tests ; Risk Assessment ; Surveys and Questionnaires ; }, abstract = {There is no universally approved method in the scientific literature to identify subjects exposed to asbestos and divide them in classes according to intensity of exposure. The aim of our work is to study and develope an algorithm based on the findings of occupational anamnestical information provided by a large group of workers. The algorithm allows to discriminate, in a probabilistic way, the risk of exposure by the attribution of a code for each worker (ELSA Code--work estimated exposure to asbestos). The ELSA code has been obtained through a synthesis of information that the international scientific literature identifies as the most predictive for the onset of asbestos-related abnormalities. Four dimensions are analyzed and described: 1) present and/or past occupation; 2) type of materials and equipment used in performing working activity; 3) environment where these activities are carried out; 4) period of time when activities are performed. Although it is possible to have informations in a subjective manner, the decisional procedure is objective and is based on the systematic evaluation of asbestos exposure. From the combination of the four identified dimensions it is possible to have 108 ELSA codes divided in three typological profiles of estimated risk of exposure. The application of the algorithm offers some advantages compared to other methods used for identifying individuals exposed to asbestos: 1) it can be computed both in case of present and past exposure to asbestos; 2) the classification of workers exposed to asbestos using ELSA code is more detailed than the one we have obtained with Job Exposure Matrix (JEM) because the ELSA Code takes in account other indicators of risk besides those considered in the JEM. This algorithm was developed for a project sponsored by the Italian Armed Forces and is also adaptable to other work conditions for in which it could be necessary to assess risk for asbestos exposure.}, } @article {pmid20684435, year = {2010}, author = {Barbieri, PG and Somigliana, A and Festa, R and Bercich, L}, title = {[Pulmonary concentration of asbestos fibers in steel workers with pleural mesothelioma].}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {32}, number = {2}, pages = {149-153}, pmid = {20684435}, issn = {1592-7830}, mesh = {Aged ; Asbestos, Amphibole/adverse effects/*analysis ; Asbestos, Serpentine/analysis ; Asbestosis/*complications/diagnosis/mortality/surgery ; Humans ; Lung/chemistry ; Male ; Mesothelioma/*chemistry/diagnosis/etiology/mortality/surgery ; *Metallurgy ; Occupational Exposure/adverse effects/*analysis ; Pleura/chemistry ; Pleural Neoplasms/*chemistry/diagnosis/etiology/mortality/surgery ; Retrospective Studies ; Risk Assessment ; }, abstract = {The asbestos fibre burden of the lung has been used in the past as a biological indicator of cumulative exposure to the mineral so much so that in 1997 reference limits even for non-occupationally exposed people have been proposed. This kind of analysis was performed on groups of workers of different type of industries and allowed to achieve a qualitative-quantitative estimate of past exposure to asbestos, even in absence of exposure estimates by environmental monitoring. An important example is the steel industry where asbestos was widely used in the past, but for which there are not available exposure estimates of workers. Among the mesothelioma cases collected by the Mesothelioma Registry of the Province of Brescia from 1980 to present there are 55 workers who spent at least 5 years in steel industry, on a total of 289 cases classified as asbestos exposed (19%). For 8 subjects who worked in steel mills and production of electrical steel pipes, of which 4 in the same plant, lung tissue samples were available for the asbestos fibres burden analysis (7 samples coming from autopsies and 1 from extra-pleural pneumonectomy). In all cases the diagnosis was given with histological analyses supplemented with immunohistochemistry. In 7 cases autopsied the diagnosis was confirmed. The work histories have been reconstructed in detail through the interview process, inclusive of details of duties performed. The asbestos fibre burden analyses showed a range of concentrations between 260,000 and 11,000,000 ff per grams of dry tissue; the concentration of amphiboles was much higher than that of chrysotile. The highest body burden was detected in the maintenance workers of the same plant in witch a cluster of malignant mesothelioma was observed. In conclusion, this study illustrates the results of asbestos fibres burden analyses in subjects where exposure to asbestos is sure but not quantifiable. The results showed also that these concentrations can reach values that overlap with those found in asbestos-cement workers and in asbestos-textile workers. These data suggest to consider the cases of mesothelioma occurred in the steel workers at least as "possible" exposure, even in the absence of adequate information on the circumstances of contact with asbestos. This study, although based on a small number of cases, is the only one ever held in Italy on workers in this sector.}, } @article {pmid20682992, year = {2010}, author = {Yasuda, M and Hanagiri, T and Shigematsu, Y and Onitsuka, T and Kuroda, K and Baba, T and Mizukami, M and Ichiki, Y and Uramoto, H and Takenoyama, M and Yasumoto, K}, title = {Identification of a tumour associated antigen in lung cancer patients with asbestos exposure.}, journal = {Anticancer research}, volume = {30}, number = {7}, pages = {2631-2639}, pmid = {20682992}, issn = {1791-7530}, mesh = {Aged ; Aged, 80 and over ; Annexin A2/biosynthesis/immunology ; Antibodies, Neoplasm/immunology ; Antigens, Neoplasm/*immunology ; Asbestos/immunology/*poisoning ; Enzyme-Linked Immunosorbent Assay ; Humans ; Immunity, Humoral/immunology ; Immunoglobulin G/immunology ; Interleukin-6/blood/immunology ; Lung Neoplasms/*etiology/*immunology ; Male ; Mesothelioma/etiology/immunology ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {BACKGROUND: This study analysed the humoral immune response in asbestos exposed lung cancer patients to identify new surrogate markers of the carcinogenic risk in populations exposed to asbestos.

METHODS AND RESULTS: A serological analysis identified five distinct antigens reactive with IgG derived from a lung cancer patient with high asbestos exposure. In one of the isolated antigens, quantitative RT-PCR indicated that annexin A2 (AnxA2) was overexpressed in lung cancer tissues and normal lung from patients with high asbestos exposure. Antibody against AnxA2 was detected in 9/15 (60%) of lung cancer patients with high asbestos exposure; however, in only 1/12 (8%) of lung cancer patients with low asbestos exposure. AnxA2 was also overexpressed in malignant mesothelioma cells, and the antibody was also positive in 8/15 (53%) of patients with malignant mesothelioma.

CONCLUSION: The antibody titer against AnxA2 may be a potentially useful new diagnostic surrogate marker for asbestos-related lung cancer and malignant mesothelioma.}, } @article {pmid20682491, year = {2010}, author = {, }, title = {Asbestos is still with us: repeat call for a universal ban.}, journal = {International journal of occupational medicine and environmental health}, volume = {23}, number = {2}, pages = {201-207}, doi = {10.2478/v10001-010-0017-4}, pmid = {20682491}, issn = {1232-1087}, mesh = {Asbestos/*adverse effects ; Asbestosis/*prevention & control ; *Global Health ; Humans ; International Cooperation ; Mining/*legislation & jurisprudence ; Occupational Exposure/*legislation & jurisprudence ; *Politics ; }, abstract = {All forms of asbestos are proven human carcinogens. All forms of asbestos cause malignant mesothelioma, lung, and laryngeal cancers, and may cause ovarian, gastrointestinal and other cancers. No exposure to asbestos is without risk, and there is no safe threshold of exposure to asbestos. Asbestos cancer victims die painful lingering deaths. These deaths are almost entirely preventable. When evidence of the carcinogenicity of asbestos became incontrovertible, the concerned parties, including the Collegium Ramazzini, called for a universal ban on the mining, manufacture and use of asbestos in all countries around the world. Asbestos is now banned in 52 countries, and safer products have replaced many materials that once were made with asbestos. Nonetheless, a large number of countries still use, import, and export asbestos and asbestos-containing products. And in many countries that have banned other forms of asbestos, the so-called "controlled use" of chrysotile asbestos continues to be permitted, an exemption that has no basis in medical science but rather reflects the political and economic influence of the asbestos mining and manufacturing industry. To protect the health of all people in the world--industrial workers, construction workers, women and children, now and in future generations--the Collegium Ramazzini calls again today on all countries of the world, as we have repeatedly in the past, to join in the international endeavor to ban all forms of asbestos. An international ban on asbestos is urgently needed.}, } @article {pmid20662427, year = {2010}, author = {, }, title = {Asbestos is still with us: repeat call for a universal ban.}, journal = {International journal of occupational and environmental health}, volume = {16}, number = {3}, pages = {351-355}, doi = {10.1179/107735210799160228}, pmid = {20662427}, issn = {1077-3525}, mesh = {Asbestos/*standards ; Commerce/legislation & jurisprudence ; Developing Countries ; Humans ; International Cooperation/*legislation & jurisprudence ; Mining/*legislation & jurisprudence/standards ; Occupational Exposure/*legislation & jurisprudence/*prevention & control ; World Health Organization ; }, abstract = {All forms of asbestos are proven human carcinogens, causing malignant mesothelioma and a host of other types of cancers. No exposure to asbestos is without risk; there is no safe threshold of exposure to asbestos. When evidence of the carcinogenicity of asbestos became incontrovertible, a worldwide ban was called for on asbestos use, mining, and manufacturing. Asbestos is now banned in 52 countries. Nonetheless, many countries still use, import, and export asbestos and asbestos-containing products; many countries that have banned other forms of asbestos still permit the use of chrysotile asbestos. This exemption has no basis in medical science, but reflects the political and economic influence of the asbestos industry. To protect the health of all people, the Collegium Ramazzini calls again on all countries of the world to join in the international endeavor to ban all forms of asbestos. An international ban on asbestos is urgently needed.}, } @article {pmid20661695, year = {2010}, author = {Kurata, S and Ishibashi, M and Azuma, K and Kaida, H and Takamori, S and Fujimoto, K and Kobayashi, M and Hirose, Y and Aizawa, H and Hayabuchi, N}, title = {Preliminary study of positron emission tomography/computed tomography and plasma osteopontin levels in patients with asbestos-related pleural disease.}, journal = {Japanese journal of radiology}, volume = {28}, number = {6}, pages = {446-452}, pmid = {20661695}, issn = {1867-108X}, mesh = {Aged ; Aged, 80 and over ; Asbestos/blood/*toxicity ; Diagnosis, Differential ; Female ; Fluorodeoxyglucose F18 ; Humans ; Imaging, Three-Dimensional/methods ; Male ; Mesothelioma/blood/*diagnostic imaging/etiology ; Middle Aged ; Osteopontin/*blood ; Pleura/diagnostic imaging ; Pleural Diseases/blood/*diagnostic imaging/etiology ; Pleural Neoplasms/blood/diagnostic imaging ; Pleurisy/blood/diagnostic imaging ; Positron-Emission Tomography/*methods ; Prospective Studies ; Radiopharmaceuticals ; Tomography, Spiral Computed/*methods ; }, abstract = {PURPOSE: The aim of this study was to compare the results of semiquantitative analysis by(18)F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) with plasma osteopontin levels in the same asbestos-related pleural disease population.

MATERIALS AND METHODS: A total of 17 patients with asbestos-related pleural disease were prospectively recruited. They underwent PET/CT, and plasma osteopontin levels were measured. The maximum standardized uptake value (SUVmax) was determined from the most active pleural lesion in each patient.

RESULTS: Malignant pleural mesothelioma (MPM) was histologically proven in 6 patients, and 11 patients had proven benign asbestos-related pleural diseases (7 pleural plaques, 4 asbestos pleurisy). Significant differences in SUVmax were found between patients with MPM and those with asbestos pleurisy (P = 0.031) and between patients with MPM and those with pleural plaques (P = 0.012). A significant difference was found in the plasma osteopontin levels between patients with asbestos pleurisy and patients with pleural plaques (Bonferroni correction, P = 0.024). The SUVmax in patients with benign asbestos-related diseases was statistically positively correlated with plasma osteopontin in the same group (Spearman's r = 0.75, P < 0.05).

CONCLUSION: PET/CT might be more helpful than plasma osteopontin for distinguishing benign asbestos-related pleural diseases from MPM, and the SUVmax in benign asbestos-related pleural diseases may reflect changes in pleural inflammation.}, } @article {pmid20657552, year = {2010}, author = {Sato, A and Torii, I and Okamura, Y and Yamamoto, T and Nishigami, T and Kataoka, TR and Song, M and Hasegawa, S and Nakano, T and Kamei, T and Tsujimura, T}, title = {Immunocytochemistry of CD146 is useful to discriminate between malignant pleural mesothelioma and reactive mesothelium.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {23}, number = {11}, pages = {1458-1466}, doi = {10.1038/modpathol.2010.134}, pmid = {20657552}, issn = {1530-0285}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; CD146 Antigen/analysis ; Diagnosis, Differential ; Epithelium/*immunology/pathology ; Female ; Humans ; *Immunohistochemistry ; Japan ; Male ; Mesothelioma/*immunology/pathology ; Middle Aged ; Pleural Effusion, Malignant/*immunology/pathology ; Pleural Neoplasms/*immunology/pathology ; Predictive Value of Tests ; Sensitivity and Specificity ; }, abstract = {Malignant pleural mesothelioma is a refractory tumor with poor prognosis associated with asbestos exposure. Pleural effusion is frequently observed in patients with malignant pleural mesothelioma, and cytological analysis is effective to detect malignant pleural mesothelioma. However, cytological discrimination between malignant pleural mesothelioma and reactive mesothelium is often difficult. Increased expression of CD146, a cell adhesion molecule, has been reported to be closely associated with an advanced stage of malignant melanoma, prostate cancer, and ovarian cancer. In this study, to evaluate the diagnostic utility of CD146 for discrimination between malignant pleural mesothelioma and reactive mesothelium, we examined immunocytochemical expression of CD146 in malignant pleural mesothelioma and reactive mesothelium using two clones of CD146 antibody, OJ79 and EPR3208, on smear specimens of effusion fluids. Immunocytochemical stains were semiquantitatively scored on the basis of immunostaining intensity (0, negative; 1, weak positive; 2, moderate positive; and 3, strong positive). CD146 expression was detected in 15 of 16 malignant pleural mesothelioma with median immunostaining score of 3 by OJ79, and in 19 of 21 malignant pleural mesothelioma with median immunostaining score of 2 by EPR3208. Strong immunoreactivity of CD146 was observed at the apposing surfaces of cell-cell interactions on the plasma membrane of mesothelioma cells. In addition, one OJ79-negative case of malignant pleural mesothelioma was positive for CD146 by EPR3208 and two EPR3208-negative cases of malignant pleural mesothelioma were CD146 positive by OJ79, showing that all 23 malignant pleural mesothelioma cases were positive for CD146 by either OJ79 or EPR3208. On the other hand, CD146 expression was undetectable in all reactive mesothelium cases by OJ79 and EPR3208. The sensitivity of OJ79 and EPR3208 was 94 and 90%, respectively, and the specificity was 100% for both clones. We propose that CD146 is a sensitive and specific immunocytochemical marker enabling differential diagnosis of malignant pleural mesothelioma from reactive mesothelium.}, } @article {pmid20652786, year = {2010}, author = {Ramazzini, C}, title = {Asbestos is still with us: repeat call for a universal ban.}, journal = {Odontology}, volume = {98}, number = {2}, pages = {97-101}, pmid = {20652786}, issn = {1618-1255}, mesh = {Asbestos/*adverse effects ; Asbestos, Serpentine/adverse effects ; Asbestosis/etiology ; *Carcinogens ; Child ; Developing Countries ; Environmental Exposure ; Female ; *Global Health ; Humans ; International Cooperation ; Mining ; Occupational Exposure ; United Nations ; World Health Organization ; }, abstract = {All forms of asbestos are proven human carcinogens. All forms of asbestos cause malignant mesothelioma, lung, laryngeal, and ovarian cancers, and may cause gastrointestinal and other cancers. No exposure to asbestos is without risk, and there is no safe threshold of exposure to asbestos. Nonetheless, a large number of countries still use, import, and export asbestos and asbestos-containing products. And still today in many countries that have banned other forms of asbestos, the so-called "controlled use" of chrysotile asbestos continues to be permitted, an exemption that has no basis in medical science but rather reflects the political and economic influence of the asbestos mining and manufacturing industry. To protect the health of all people in the world - industrial workers, construction workers, dental professionals, women, and children, now and in future generations - the Collegium Ramazzini calls again today on all countries of the world, as we have repeatedly in the past, to join in the international endeavor to ban all forms of asbestos. An international ban on asbestos is urgently needed.}, } @article {pmid20651076, year = {2010}, author = {Creaney, J and Olsen, NJ and Brims, F and Dick, IM and Musk, AW and de Klerk, NH and Skates, SJ and Robinson, BW}, title = {Serum mesothelin for early detection of asbestos-induced cancer malignant mesothelioma.}, journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology}, volume = {19}, number = {9}, pages = {2238-2246}, doi = {10.1158/1055-9965.EPI-10-0346}, pmid = {20651076}, issn = {1538-7755}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Biomarkers, Tumor/*blood ; Case-Control Studies ; Early Detection of Cancer/methods ; Female ; GPI-Linked Proteins/blood ; Humans ; Male ; Membrane Glycoproteins/*blood ; Mesothelin ; Mesothelioma/*blood/*etiology/pathology ; Middle Aged ; Retrospective Studies ; }, abstract = {BACKGROUND: Malignant mesothelioma is an aggressive, almost uniformly fatal tumor, primarily caused by exposure to asbestos. Since the recent discovery that serum mesothelin is a sensitive and highly specific biomarker for mesothelioma, one of the key issues raised is whether mesothelin levels represent a useful screening test for asbestos-exposed at-risk individuals. In this study, soluble mesothelin was determined in sequential serum samples collected from asbestos-exposed individuals before the development of mesothelioma.

METHODS: Archival serum samples from 106 individuals who developed mesothelioma, 99 asbestos-exposed individuals from the Wittenoom Cancer Surveillance Program, and 109 non-asbestos-exposed individuals from the Busselton Health Survey were identified. Serum mesothelin concentrations were determined using the MESOMARK assay.

RESULTS: Longitudinal mesothelin levels determined in healthy asbestos-exposed individuals over a period of 4 years were stable (Pearson's r = 0.96; P < 0.0001). There was no correlation between mesothelin concentration and cumulative asbestos exposure. Mesothelin concentrations were greater than the threshold value of 2.5 nmol/L in the penultimate serum sample before the diagnosis of mesothelioma in 17 of 106 people. Using an increase above the 95% confidence interval of the mean of a given individual's longitudinal mesothelin results, 33 of 82 individuals had increasing mesothelin levels before diagnosis.

CONCLUSION: In a population with a high pretest probability of developing mesothelioma, the serum biomarker mesothelin is elevated in absolute terms in 15% and in relative terms in 40% of the group.

IMPACT: Future studies examining a combination of biomarkers could improve sensitivity of screening.}, } @article {pmid20628377, year = {2010}, author = {Tan, E and Warren, N and Darnton, AJ and Hodgson, JT}, title = {Projection of mesothelioma mortality in Britain using Bayesian methods.}, journal = {British journal of cancer}, volume = {103}, number = {3}, pages = {430-436}, pmid = {20628377}, issn = {1532-1827}, mesh = {Adult ; Aged ; Aged, 80 and over ; Algorithms ; Bayes Theorem ; Environmental Exposure ; Female ; Humans ; Male ; Markov Chains ; Mesothelioma/*mortality ; Middle Aged ; Models, Biological ; Monte Carlo Method ; Poisson Distribution ; Predictive Value of Tests ; Regression Analysis ; Sex Characteristics ; Time Factors ; United Kingdom/epidemiology ; Young Adult ; }, abstract = {BACKGROUND: Mesothelioma mortality has increased more than ten-fold over the past 40 years in Great Britain, with >1700 male deaths recorded in the British mesothelioma register in 2006. Annual mesothelioma deaths now account for >1% of all cancer deaths. A Poisson regression model based on a previous work by Hodgson et al has been fitted, which has allowed informed statistical inferences about model parameters and predictions of future mesothelioma mortality to be made.

METHODS: In the Poisson regression model, the mesothelioma risk of an individual depends on the average collective asbestos dose for the individual in a given year and an age-specific exposure potential. The model has been fitted to the data within a Bayesian framework using the Metropolis-Hastings algorithm, a Markov Chain Monte Carlo technique, providing credible intervals for model parameters as well as prediction intervals for the number of future cases of mortality.

RESULTS: Males were most likely to have been exposed to asbestos between the ages of 30 and 49 years, with the peak year of asbestos exposure estimated to be 1963. The estimated number of background cases was 1.08 cases per million population.

CONCLUSION: Mortality among males is predicted to peak at approximately 2040 deaths in the year 2016, with a rapid decline thereafter. Approximately 91,000 deaths are predicted to occur from 1968 to 2050 with around 61,000 of these occurring from 2007 onwards.}, } @article {pmid20621889, year = {2010}, author = {, }, title = {Asbestos is still with us: repeat call for a universal ban.}, journal = {New solutions : a journal of environmental and occupational health policy : NS}, volume = {20}, number = {2}, pages = {257-266}, doi = {10.2190/NS.20.2.j}, pmid = {20621889}, issn = {1048-2911}, mesh = {Asbestos/*toxicity ; Asbestos, Serpentine/toxicity ; Environmental Exposure/*adverse effects/*legislation & jurisprudence ; *International Cooperation ; Lung Neoplasms/*chemically induced ; Mesothelioma/*chemically induced ; Occupational Exposure/adverse effects/legislation & jurisprudence ; United Nations ; }, abstract = {All forms of asbestos are proven human carcinogens. All forms of asbestos cause malignant mesothelioma, lung, laryngeal, and ovarian cancers, and may cause gastrointestinal and other cancers. No exposure to asbestos is without risk, and there is no safe threshold of exposure to asbestos. Asbestos cancer victims die painful lingering deaths. These deaths are almost entirely preventable. When evidence of the carcinogenicity of asbestos became incontrovertible, concerned parties, including the Collegium Ramazzini, called for a universal ban on the mining, manufacture and use of asbestos in all countries around the world [1]. Asbestos is now banned in 52 countries [2], and safer products have replaced many materials that once were made with asbestos. Nonetheless, a large number of countries still use, import, and export asbestos and asbestos-containing products. And still today in many countries that have banned other forms of asbestos, the so-called "controlled use" of chrysotile asbestos continues to be permitted, an exemption that has no basis in medical science but rather reflects the political and economic influence of the asbestos mining and manufacturing industry. To protect the health of all people in the world-industrial workers, construction workers, women and children, now and in future generations-the Collegium Ramazzini calls again today on all countries of the world, as we have repeatedly in the past to join in the international endeavor to ban all forms of asbestos. An international ban on asbestos is urgently needed. New Solutions is one of ten international journals that have agreed to publish the Repeat Call in order to bring the message to a wide readership.}, } @article {pmid20618734, year = {2010}, author = {Kawai, T and Hiroi, S and Nakanishi, K and Takagawa, K and Haba, R and Hayashi, K and Kawachi, K and Nozawa, A and Hebisawa, A and Nakatani, Y}, title = {Lymphohistiocytoid mesothelioma of the pleura.}, journal = {Pathology international}, volume = {60}, number = {8}, pages = {566-574}, doi = {10.1111/j.1440-1827.2010.02560.x}, pmid = {20618734}, issn = {1440-1827}, mesh = {Biomarkers, Tumor/genetics/metabolism ; Female ; Herpesvirus 4, Human/genetics/metabolism ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Male ; Mesothelioma/genetics/metabolism/*pathology ; Microscopy, Electron ; Middle Aged ; Pleural Neoplasms/genetics/metabolism/*pathology ; RNA, Viral/genetics/metabolism ; }, abstract = {Lymphohistiocytoid mesothelioma (LHM), reported to be a rare variant of sarcomatoid mesothelioma, is challenging to differentiate from non-Hodgkin's lymphoma due to marked lymphocytic infiltration. To aid accurate recognition of LHM, we examined immunohistochemical, in situ hybridization (ISH) of Epstein-Barr virus RNA (EBER-1) mRNA, fluorescence ISH (FISH) for homozygous deletion of 9p21, and asbestos analysis in four cases (three men and 1 woman). Three patients died, while Case 4 was still alive 19 months after extrapleural pneumonectomy. Histologically, these cases were characterized by heavy lymphocytic infiltration. All neoplastic cells were positive for calretinin, AE1/AE3, and epithelial membrane antigen, but negative for CEA. EBER1 factor was negative. FISH analysis demonstrated homozygous deletion of the 9p21 locus in three of the four cases. In Case 1: (i) autopsy findings showed mesothelioma primarily located in the right parietal pleura, but metastasized into the left lung and abdominal organs; (ii) the histological findings at autopsy indicated sarcomatoid mesothelioma; and (iii) we found asbestos bodies and fibers in extracts from lung tissue (Cases 1 & 4) using digestion with bleaching fluid. LHM, an infrequent variant of sarcomatoid mesothelioma, displayed homozygous deletion of the 9p21 locus (three of four cases), and has a relatively favorable prognosis for the sarcomatoid type.}, } @article {pmid20617513, year = {2011}, author = {Hasegawa, S and Koshikawa-Yano, M and Saito, S and Morokoshi, Y and Furukawa, T and Aoki, I and Saga, T}, title = {Molecular imaging of mesothelioma by detection of manganese-superoxide dismutase activity using manganese-enhanced magnetic resonance imaging.}, journal = {International journal of cancer}, volume = {128}, number = {9}, pages = {2138-2146}, doi = {10.1002/ijc.25547}, pmid = {20617513}, issn = {1097-0215}, mesh = {Animals ; Blotting, Western ; Cell Line, Tumor ; Disease Models, Animal ; Humans ; Immunohistochemistry ; Magnetic Resonance Imaging/*methods ; Mesothelioma/*diagnosis/*enzymology ; Mice ; Mice, Nude ; Pleural Neoplasms/diagnosis/enzymology ; Reverse Transcriptase Polymerase Chain Reaction ; Superoxide Dismutase/*metabolism ; }, abstract = {Malignant mesothelioma (MM) is a fatal malignancy with a rapidly increasing incidence in industrialized countries because of the widespread use of asbestos in the past centuries. Early diagnosis of MM is critical for a better prognosis, but this is often difficult because of the lack of disease-specific diagnostic imaging. Here, we report that manganese-enhanced magnetic resonance imaging (MEMRI) represents a promising approach for a more selective mesothelioma imaging by monitoring a high-level expression of manganese-superoxide dismutase (Mn-SOD), which is observed in many MM. We found that most human MM cells overexpressed Mn-SOD protein compared with human mesothelial cells and that NCI-H226 human MM cells highly expressed Mn-SOD and augmented Mn accumulation when loaded with manganese chloride (MnCl(2)). The cells showed marked T(1)-signal enhancement on in vitro MRI after incubation with MnCl(2) because of the T(1) shortening effect of Mn(2+). H226 subcutaneous tumor was preferentially enhanced compared with a lung adenocarcinoma cell tumor and another human MM cell tumor in MnCl(2)-enhanced T(1)-weighted MR image (T(1)WI), correlating with their respective Mn-SOD expression levels. Moreover, in a more clinically relevant setting, H226 xenografted pleural tumor was markedly enhanced and readily detected by MEMRI using manganese dipyridoxyl diphosphate (MnDPDP), a clinically used contrast agent, as well as MnCl(2). Therefore, we propose that MEMRI can be a potentially powerful method for noninvasive detection of MM, with high spatial resolution and marked signal enhancement, by targeting Mn-SOD.}, } @article {pmid20616036, year = {2010}, author = {Yang, H and Rivera, Z and Jube, S and Nasu, M and Bertino, P and Goparaju, C and Franzoso, G and Lotze, MT and Krausz, T and Pass, HI and Bianchi, ME and Carbone, M}, title = {Programmed necrosis induced by asbestos in human mesothelial cells causes high-mobility group box 1 protein release and resultant inflammation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {107}, number = {28}, pages = {12611-12616}, pmid = {20616036}, issn = {1091-6490}, mesh = {Adenosine Diphosphate Ribose/metabolism/pharmacology ; Animals ; Asbestos/metabolism/pharmacology ; Carcinogens/metabolism/pharmacology ; Cell Death ; Cell Nucleus/metabolism ; Cells/metabolism ; Cricetinae ; Cytokines/metabolism/pharmacology ; Epithelial Cells/metabolism ; Epithelium/drug effects/metabolism ; Female ; HMGB Proteins/metabolism/pharmacology ; HMGB1 Protein/*metabolism/pharmacology ; Humans ; Hydrogen Peroxide/metabolism/pharmacology ; Inflammation/*metabolism ; Macrophages/metabolism ; Mesocricetus ; Mesothelioma/metabolism ; Mice ; Mice, Inbred BALB C ; Necrosis/metabolism ; Pleural Neoplasms/metabolism ; Poly Adenosine Diphosphate Ribose/pharmacology ; Poly(ADP-ribose) Polymerases/metabolism/pharmacology ; Reactive Oxygen Species/metabolism/pharmacology ; Tumor Necrosis Factor-alpha/metabolism/pharmacology ; }, abstract = {Asbestos carcinogenesis has been linked to the release of cytokines and mutagenic reactive oxygen species (ROS) from inflammatory cells. Asbestos is cytotoxic to human mesothelial cells (HM), which appears counterintuitive for a carcinogen. We show that asbestos-induced HM cell death is a regulated form of necrosis that links to carcinogenesis. Asbestos-exposed HM activate poly(ADP-ribose) polymerase, secrete H(2)O(2), deplete ATP, and translocate high-mobility group box 1 protein (HMGB1) from the nucleus to the cytoplasm, and into the extracellular space. The release of HMGB1 induces macrophages to secrete TNF-alpha, which protects HM from asbestos-induced cell death and triggers a chronic inflammatory response; both favor HM transformation. In both mice and hamsters injected with asbestos, HMGB1 was specifically detected in the nuclei, cytoplasm, and extracellular space of mesothelial and inflammatory cells around asbestos deposits. TNF-alpha was coexpressed in the same areas. HMGB1 levels in asbestos-exposed individuals were significantly higher than in nonexposed controls (P < 0.0001). Our findings identify the release of HMGB1 as a critical initial step in the pathogenesis of asbestos-related disease, and provide mechanistic links between asbestos-induced cell death, chronic inflammation, and carcinogenesis. Chemopreventive approaches aimed at inhibiting the chronic inflammatory response, and especially blocking HMGB1, may decrease the risk of malignant mesothelioma among asbestos-exposed cohorts.}, } @article {pmid20601329, year = {2010}, author = {LaDou, J and Castleman, B and Frank, A and Gochfeld, M and Greenberg, M and Huff, J and Joshi, TK and Landrigan, PJ and Lemen, R and Myers, J and Soffritti, M and Soskolne, CL and Takahashi, K and Teitelbaum, D and Terracini, B and Watterson, A}, title = {The case for a global ban on asbestos.}, journal = {Environmental health perspectives}, volume = {118}, number = {7}, pages = {897-901}, pmid = {20601329}, issn = {1552-9924}, mesh = {Asbestos, Serpentine/*adverse effects ; Carcinogens, Environmental/*adverse effects ; *Environmental Exposure ; Environmental Health/*legislation & jurisprudence ; *Global Health ; Humans ; International Cooperation/legislation & jurisprudence ; Mining/legislation & jurisprudence ; Neoplasms/*chemically induced/*epidemiology ; *Occupational Exposure ; }, abstract = {BACKGROUND: All forms of asbestos are now banned in 52 countries. Safer products have replaced many materials that once were made with it. Nonetheless, many countries still use, import, and export asbestos and asbestos-containing products, and in those that have banned other forms of asbestos, the so-called "controlled use" of chrysotile asbestos is often exempted from the ban. In fact, chrysotile has accounted for > 95% of all the asbestos used globally.

OBJECTIVE: We examined and evaluated the literature used to support the exemption of chrysotile asbestos from the ban and how its exemption reflects the political and economic influence of the asbestos mining and manufacturing industry.

DISCUSSION: All forms of asbestos, including chrysotile, are proven human carcinogens. All forms cause malignant mesothelioma and lung and laryngeal cancers, and may cause ovarian, gastrointestinal, and other cancers. No exposure to asbestos is without risk. Illnesses and deaths from asbestos exposure are entirely preventable.

CONCLUSIONS: All countries of the world have an obligation to their citizens to join in the international endeavor to ban the mining, manufacture, and use of all forms of asbestos. An international ban is urgently needed. There is no medical or scientific basis to exempt chrysotile from the worldwide ban of asbestos.}, } @article {pmid20601327, year = {2010}, author = {Lemen, RA}, title = {Chrysotile asbestos and mesothelioma.}, journal = {Environmental health perspectives}, volume = {118}, number = {7}, pages = {A282}, pmid = {20601327}, issn = {1552-9924}, mesh = {Asbestos, Serpentine/*adverse effects ; Humans ; Mesothelioma/*epidemiology/*etiology ; }, } @article {pmid20599674, year = {2010}, author = {Nagai, H and Toyokuni, S}, title = {Biopersistent fiber-induced inflammation and carcinogenesis: lessons learned from asbestos toward safety of fibrous nanomaterials.}, journal = {Archives of biochemistry and biophysics}, volume = {502}, number = {1}, pages = {1-7}, doi = {10.1016/j.abb.2010.06.015}, pmid = {20599674}, issn = {1096-0384}, mesh = {Animals ; Asbestos/*adverse effects ; Humans ; In Vitro Techniques ; Inflammation/*etiology ; Macrophage Activation ; Mesothelioma/etiology ; Mineral Fibers/adverse effects ; Models, Biological ; Nanostructures/*adverse effects/ultrastructure ; Nanotubes, Carbon/adverse effects/ultrastructure ; Neoplasms/*etiology ; }, abstract = {Nano-sized durable fibrous materials such as carbon nanotubes have raised safety concerns similar to those raised by asbestos. However, the mechanism by which particulates with ultrafine structure cause inflammation and ultimately cancer (e.g. malignant mesothelioma and lung cancer) is largely unknown. This is partially because the particulates are not uniform and they vary in a plethora of factors. Such variances include length, diameter, surface area, density, shape, contaminant metals (including iron) and crystallinity. Each of these factors is involved in particulate toxicity both in vitro and in vivo. Thus, the elicited biological responses are incredibly complicated. Various kinds of fibers were evaluated with different cells, animals and methods. The aim of this review is to concisely summarize previous reports from the standpoint that activation of macrophages and mesothelial injury are the two major mechanisms of inflammation and possibly cancer. Importantly, these two mechanisms appear to be interacting with each other. However, there is a lack of data on the interplay of macrophage and mesothelium especially in vivo. Since fibrous nanomaterials present potential applications in various fields, it is necessary to develop standard evaluation methods to minimize risks for human health.}, } @article {pmid20595729, year = {2010}, author = {Vanotto, A}, title = {[Asbestos victims still in search of justice: the battle of AIEA (Italian Association of the Exposed to Asbestos)].}, journal = {Epidemiologia e prevenzione}, volume = {34}, number = {1-2}, pages = {15-16}, pmid = {20595729}, issn = {1120-9763}, mesh = {Asbestos/*adverse effects ; Asbestosis/*etiology/mortality/*prevention & control ; Automobiles/*legislation & jurisprudence ; Biomedical Research/legislation & jurisprudence ; Humans ; Industry/*legislation & jurisprudence/organization & administration ; Italy/epidemiology ; Mass Screening/legislation & jurisprudence ; Mesothelioma/etiology/prevention & control ; *Occupational Health ; Pleural Neoplasms/etiology/prevention & control ; Politics ; Population Surveillance ; Registries/statistics & numerical data ; }, } @article {pmid20593749, year = {2010}, author = {Pala, C and Paliogiannis, P and Serventi, F and Trignano, E and Trignano, M}, title = {Multimodality approach to malignant pleural mesothelioma. A case report.}, journal = {Annali italiani di chirurgia}, volume = {81}, number = {1}, pages = {37-40}, pmid = {20593749}, issn = {0003-469X}, mesh = {Aged ; Combined Modality Therapy ; Humans ; Male ; Mesothelioma/*therapy ; Pleural Neoplasms/*therapy ; }, abstract = {INTRODUCTION: We report a case of diffuse malignant pleural mesothelioma (DMPM) in a 68-years-old male patient who was admitted for right sited pleural effusion. The patient was treated by multimodality approach consisting in surgical treatment with Extrapleural Pleuropneumonectomy followed by chemotherapy with Cisplatin and Pemetrexed. He had a disease free period of one year and survived for 31 months.

CASE REPORT: The patient was admitted to our Institute for a right sited pleural effusion diagnosed on chest X ray. Anamnesis revealed professional asbestos exposure and the patient presented dyspnea, dry cough, right sited chest pain, low fever and loss of weight. As thoracentesis and CT scan did not reveal pathological findings except of the effusion, we performed videothoracoscopy. Several grey nodular lesions involving the costal, diaphragmatic and mediastinic parietal pleural sheets were found. Histological examination of the specimens extracted revealed the presence of epithelial malignant pleural mesothelioma with sarcomatoid areas. Further examinations staged the lesion as Butchart I. Extrapleural pleuropneumonectomy was performed followed by a chemiotherapic treatment with Cisplatin and Pemetrexed. The patient underwent a follow up program with CT scan every four months. The disease free period was of about one year and the patient died after 31 months from diagnosis for septic complications related to chronic effusion.

DISCUSSION: Single treatments do not demonstrate an acceptable efficacy on the treatment of DMPM. Multimodality therapy provides good survival improvement and acceptable quality of life for the patients.}, } @article {pmid20591913, year = {2010}, author = {Chung, CT and Santos, Gda C and Hwang, DM and Ludkovski, O and Pintilie, M and Squire, JA and Tsao, MS}, title = {FISH assay development for the detection of p16/CDKN2A deletion in malignant pleural mesothelioma.}, journal = {Journal of clinical pathology}, volume = {63}, number = {7}, pages = {630-634}, pmid = {20591913}, issn = {1472-4146}, mesh = {Asbestos/adverse effects ; Biopsy ; Female ; *Gene Deletion ; *Genes, p16 ; Humans ; In Situ Hybridization, Fluorescence/*methods ; Male ; Mesothelioma/*diagnosis/etiology/genetics/pathology ; Middle Aged ; Pleural Neoplasms/*diagnosis/etiology/genetics/pathology ; Prognosis ; Prospective Studies ; Smoking/adverse effects ; Survival Analysis ; }, abstract = {AIMS: To develop a fluorescence in-situ hybridisation (FISH) assay for detecting p16/CDKN2A deletion on paraffin tissue sections for use as an ancillary test to distinguish reactive from malignant mesothelial proliferations.

METHOD: Dual-colour FISH for p16/CDKN2A and chromosome 9 (CEP-9) was performed on 11 benign mesothelial proliferations and 54 malignant pleural mesothelioma (MPM) cases to establish cut-off values for p16/CDKN2A deletion. A third MYC probe was used to verify cases showing homozygous deletion. Eight equivocal biopsies were used for assay testing.

RESULTS: Cut-off values for p16/CDKN2A deletion were calculated based on FISH signalling patterns obtained from the benign controls (mean percent nuclei plus three standard deviations). Hemizygous deletion was defined as >44% of nuclei showing the hemizygous (one p16/CDKN2A, two CEP-9 signals) or >15% of nuclei showing the monosomy (one p16/CDKN2A, one CEP-9 signal) deletion patterns. None of the benign cases showed a homozygous deletion pattern (no p16/CDKN2A, at least one CEP-9 signal). In the malignant cases, the percentage of nuclei showing homozygous deletion ranged from 1% to 87%. Therefore, the cut-off value for homozygous deletion was defined as >10%. P16/CDKN2A deletion was detected in 61% (33/54) of MPM cases. Among the equivocal biopsies, four showed homozygous and one showed hemizygous p16/CDKN2A deletion. Age over 60 years, asbestos exposure and p16/CDKN2A deletion were associated with a worse prognosis.

CONCLUSION: Distinction between benign and malignant mesothelial proliferations can be diagnostically challenging. FISH for p16/CDKN2A deletion is a useful test for confirming the diagnosis of MPM.}, } @article {pmid22966348, year = {2010}, author = {Yokohira, M and Hashimoto, N and Yamakawa, K and Suzuki, S and Saoo, K and Kuno, T and Imaida, K}, title = {Potassium octatitanate fibers (TISMO) induce pleural mesothelial cell reactions with iron accumulation in female A/J mice.}, journal = {Oncology letters}, volume = {1}, number = {4}, pages = {589-594}, pmid = {22966348}, issn = {1792-1074}, abstract = {It is crucial to develop therapeutic approaches for malignant mesothelioma, as well as to obtain information involving the possible mechanism involved in the development of mesothelioma. Subsequently, thoracotomy was performed to infuse test particles directly into the thoracic cavity of A/J mice. Fiber-shaped particles of potassium octatitanate (TISMO) and granular-shaped micro- and nano-size order particles of titanium dioxide (TiO(2)) were employed (1.5 mg in 0.2 ml saline/mouse). The experiment was terminated after 21 weeks to assess responses. Only the fiber-shaped TISMO, morphologically similar to asbestos, induced a severe reaction of the pleura. A number of TISMO fibers were observed in the alveoli, indicating penetration through the pleura. Following Berlin blue staining, positive spots were observed around the TISMO fibers, indicative of iron. These positive spots corresponded with cells that immunostained positively for calretinin, a marker of mesothelial cells. Similar observations were reported for asbestos-induced mesothelioma. The present study showed that only fiber-shaped TISMO induced severe reactions of the mesothelium in the pleura, and these involved iron accumulation derived from endogenous sources. The results indicate that the risk of mesothelial cell reaction does not depend on particle size, but may depend on shape.}, } @article {pmid20587528, year = {2010}, author = {Christensen, BC and Houseman, EA and Poage, GM and Godleski, JJ and Bueno, R and Sugarbaker, DJ and Wiencke, JK and Nelson, HH and Marsit, CJ and Kelsey, KT}, title = {Integrated profiling reveals a global correlation between epigenetic and genetic alterations in mesothelioma.}, journal = {Cancer research}, volume = {70}, number = {14}, pages = {5686-5694}, pmid = {20587528}, issn = {1538-7445}, support = {R01 CA126939-04/CA/NCI NIH HHS/United States ; R01CA100679/CA/NCI NIH HHS/United States ; R01CA126939/CA/NCI NIH HHS/United States ; R01 CA100679/CA/NCI NIH HHS/United States ; R01 CA100679-08/CA/NCI NIH HHS/United States ; R01 CA126939/CA/NCI NIH HHS/United States ; }, mesh = {Alleles ; DNA (Cytosine-5-)-Methyltransferase 1 ; DNA (Cytosine-5-)-Methyltransferases/genetics ; DNA Methylation ; Epigenesis, Genetic ; Gene Dosage ; Gene Expression Profiling ; Humans ; Mesothelioma/enzymology/*genetics ; Pilot Projects ; Pleural Neoplasms/enzymology/*genetics ; Polymorphism, Single Nucleotide ; }, abstract = {Development of mesothelioma is linked mainly to asbestos exposure, but the combined contributions of genetic and epigenetic alterations are unclear. We investigated the potential relationships between gene copy number (CN) alterations and DNA methylation profiles in a case series of pleural mesotheliomas (n = 23). There were no instances of significantly correlated CN alteration and methylation at probed loci, whereas averaging loci over their associated genes revealed only two genes with significantly correlated CN and methylation alterations. In contrast to the lack of discrete correlations, the overall extent of tumor CN alteration was significantly associated with DNA methylation profile when comparing CN alteration extent among methylation profile classes. Further, there was evidence that this association was partially attributable to prevalent allele loss at the DNA methyltransferase gene DNMT1. Our findings define a strong association between global genetic and global epigenetic dysregulation in mesothelioma, rather than a discrete, local coordination of gene inactivation.}, } @article {pmid20571403, year = {2010}, author = {Alfonso, HS and Reid, A and de Klerk, NH and Olsen, N and Mina, R and Ambrosini, GL and Beilby, J and Berry, G and Musk, BA}, title = {Retinol supplementation and mesothelioma incidence in workers earlier exposed to blue asbestos (Crocidolite) at Wittenoom, Western Australia.}, journal = {European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP)}, volume = {19}, number = {5}, pages = {355-359}, doi = {10.1097/CEJ.0b013e32833c1bcb}, pmid = {20571403}, issn = {1473-5709}, mesh = {Asbestos, Crocidolite/*toxicity ; Female ; Follow-Up Studies ; Humans ; Incidence ; Male ; Mesothelioma/*epidemiology/etiology/prevention & control ; Middle Aged ; Mining ; Occupational Diseases/*epidemiology/etiology/prevention & control ; *Occupational Exposure ; Program Evaluation ; Smoking/epidemiology ; Vitamin A/*administration & dosage ; Western Australia/epidemiology ; }, abstract = {Owing to the high rates of malignant mesothelioma in workers exposed to crocidolite earlier at Wittenoom and evidence of protection against cancer by vitamin A, a population-based cancer prevention programme providing retinol supplements (25 000 IU/day) was commenced in 1990. The former workers at Wittenoom known to be alive and living in Western Australia in June 1990 constitute the study population. The participants were classified into two groups: those who received supplemental retinol (intervention group) and those who received none (comparison group). The relative rate of mesothelioma for those receiving retinol was estimated using Cox regression, adjusting for cumulative asbestos exposure and age at first exposure to asbestos. Nine hundred and twenty-eight former Wittenoom workers received retinol at some stage of the programme, whereas 1471 workers never received retinol (comparison group). Those who received retinol were younger, had a greater exposure to asbestos and smoked less than the comparison group. There were 65 cases of mesothelioma in the retinol group and 88 in the comparison group. After adjustment, the hazard ratio was 0.99 (95% confidence interval=0.70-1.41). This result did not alter when the participants who received only retinol once or those who received beta-carotene earlier were excluded from the analysis. In conclusion, this study provides little support for possible preventive effects of retinol against mesothelioma in workers exposed to blue asbestos.}, } @article {pmid20564517, year = {2010}, author = {Kishimoto, T and Gemba, K and Fujimoto, N and Aoe, K and Kato, K and Takeshima, Y and Inai, K}, title = {Clinical study on mesothelioma in Japan: Relevance to occupational asbestos exposure.}, journal = {American journal of industrial medicine}, volume = {53}, number = {11}, pages = {1081-1087}, doi = {10.1002/ajim.20868}, pmid = {20564517}, issn = {1097-0274}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Chi-Square Distribution ; Female ; Humans ; Japan/epidemiology ; Kaplan-Meier Estimate ; Male ; Medical Records ; Mesothelioma/classification/diagnosis/*etiology/mortality ; Middle Aged ; Neoplasms/classification/diagnosis/*etiology/mortality ; Occupational Exposure/*adverse effects ; Retrospective Studies ; Surveys and Questionnaires ; Workers' Compensation ; Young Adult ; }, abstract = {BACKGROUND: In 2003, the number of deaths due to malignant mesothelioma in Japan was 878; however, only 85 cases of mesothelioma due to asbestos exposure were authorized for compensation. The reasons for this discrepancy require evaluation.

METHOD: We examined medical records, X-rays, and pathology results to evaluate mesothelioma cases in Japan between 2003 and 2005; used a questionnaire to identify occupational and environmental histories, and determined the concentration of asbestos fibers in pathology specimens.

RESULTS: We identified 442 definite cases of malignant mesothelioma with a median age of 68 years. There were 316 malignant mesothelioma cases with occupational asbestos exposure, 12 cases with neighborhood exposure and 5 cases with likely domestic exposure. Most (78%) of the 87 cases exceeded 1,000 asbestos particles per gram of dry lung tissue.

CONCLUSION: We conclude that 79.2% of cases of mesothelioma in Japan in recent years were caused by asbestos exposure.}, } @article {pmid20557009, year = {2010}, author = {Kotela, I and Bednarenko, M and Wilk-Frańczuk, M and Kotela, P and Wołowiec, B and Laskowicz, K}, title = {[The effects of environmental exposure to asbestos dust on health].}, journal = {Przeglad lekarski}, volume = {67}, number = {2}, pages = {107-109}, pmid = {20557009}, issn = {0033-2240}, mesh = {Air Pollutants/adverse effects/*analysis ; Asbestos/adverse effects/*analysis ; Dust/analysis ; Environmental Exposure/adverse effects/*analysis ; Environmental Monitoring/*statistics & numerical data ; Epidemiological Monitoring ; Female ; Humans ; Male ; Mesothelioma/etiology/*mortality ; Occupational Diseases/etiology/*mortality ; Occupational Exposure/analysis ; Pleural Neoplasms/etiology/*mortality ; Poland/epidemiology ; Risk Assessment ; Survival Rate ; }, abstract = {Pleural mesothelioma is an extremely rare neoplasm. Its etiology is related to professional or environmental exposure to asbestos dust. In the present research, the analysis of frequency and causes of death due to asbestos-related cancers in the district polluted with asbestos in comparison with the district free of such pollution has been performed. The increase has been highlighted in the mortality rate because of pleural mesothelioma among inhabitants of the area polluted with asbestos wastes.}, } @article {pmid20537223, year = {2010}, author = {Rinaudo, C and Croce, A and Musa, M and Fornero, E and Allegrina, M and Trivero, P and Bellis, D and Sferch, D and Toffalorio, F and Veronesi, G and Pelosi, G}, title = {Study of inorganic particles, fibers, and asbestos bodies by variable pressure scanning electron microscopy with annexed energy dispersive spectroscopy and micro-Raman spectroscopy in thin sections of lung and pleural plaque.}, journal = {Applied spectroscopy}, volume = {64}, number = {6}, pages = {571-577}, doi = {10.1366/000370210791414380}, pmid = {20537223}, issn = {1943-3530}, mesh = {Asbestos/*analysis ; Humans ; Lung/*pathology ; Lung Neoplasms/*pathology ; Mesothelioma/*pathology ; Microscopy, Electron, Scanning/*methods ; Pleural Diseases/pathology ; Spectrum Analysis, Raman/*methods ; }, abstract = {In a previous work it has been demonstrated that micro-Raman spectroscopy is a technique able to recognize crystalline phases on untreated samples. In that case, inorganic particles and uncoated fibers from bronchoalveolar lavage (BAL) of a patient affected by pneumoconiosis were identified and characterized. In this work the technique is applied to asbestos bodies, that is, to coated fibers, and on crystallizations and fibrous phases observed in the plural plaque from patients affected by mesothelioma. From the Raman analysis the abundant fibrous material observed in the pleural area is talc, whereas rounded grains in the pleural tissue show the Raman spectrum of apatite, a calcium phosphate mineral particular to bones. In the pulmonary tissue many asbestos bodies, consisting of the incorporated fibers coated by iron-rich proteins, were observed. Under the 632.8 nm laser beam of the spectrometer, photo-crystallization of hematite in the iron-rich material forming the asbestos bodies can be proposed by the changes in the Raman spectra acquired during subsequent acquisitions. Nevertheless, the identification of the mineral phase constituting the incorporated fiber was possible by analyzing the Raman spectra; the results were confirmed by variable pressure scanning electron microscopy with annexed energy dispersive spectroscopy (VP-SEM-EDS) analyses.}, } @article {pmid20530447, year = {2010}, author = {Rizzardi, C and Barresi, E and Brollo, A and Cassetti, P and Schneider, M and Melato, M}, title = {Primary pericardial mesothelioma in an asbestos-exposed patient with previous heart surgery.}, journal = {Anticancer research}, volume = {30}, number = {4}, pages = {1323-1325}, pmid = {20530447}, issn = {1791-7530}, mesh = {Aged ; Asbestos/*adverse effects ; *Cocarcinogenesis ; Coronary Artery Bypass/*adverse effects ; Heart Neoplasms/*etiology ; Humans ; Inflammation/etiology ; Male ; Mesothelioma/*etiology ; Pericardiectomy/*adverse effects ; }, abstract = {We present a case of primary pericardial mesothelioma occurring in an asbestos-exposed 67-year-old man who underwent four aortocoronary bypass grafting seven years prior to the onset of the mesothelioma. Primary pericardial mesothelioma is a rare tumor whose association with asbestos is more infrequent than that of the much more common pleural form. Factors other than asbestos that may play a role include genetic predisposition, immune impairment, infections, radiation, dietary factors, and recurrent serosal inflammation. We consider that, in the presented case, inflammation and healing resulting from pericardiotomy might have had a synergistic effect with asbestos in the pathogenesis of the tumor. To our knowledge, this is the first reported case of primary pericardial mesothelioma arising in a patient exposed to asbestos who previously underwent cardiac surgery.}, } @article {pmid20522822, year = {2010}, author = {Goldberg, S and Rey, G and Luce, D and Gilg Soit Ilg, A and Rolland, P and Brochard, P and Imbernon, E and Goldberg, M}, title = {Possible effect of environmental exposure to asbestos on geographical variation in mesothelioma rates.}, journal = {Occupational and environmental medicine}, volume = {67}, number = {6}, pages = {417-421}, doi = {10.1136/oem.2009.050336}, pmid = {20522822}, issn = {1470-7926}, mesh = {Asbestos/*toxicity ; Environmental Exposure/*adverse effects ; Female ; France/epidemiology ; Humans ; Incidence ; Male ; Mesothelioma/*epidemiology/etiology/mortality ; Pleural Neoplasms/*epidemiology/etiology/mortality ; Sex Distribution ; }, abstract = {BACKGROUND: In population-based mesothelioma studies in industrialised countries, the incidence of mesothelioma without any identified asbestos exposure (IAE) is usually higher among women, while male incidence is mainly attributed to IAE. Through a comparison of the spatial distribution of male and female rates, and IAE and no IAE incidence, this study investigated whether mesotheliomas without IAE are in fact induced by non-recognised asbestos exposure, mostly from environmental sources.

METHODS: We calculated mesothelioma mortality (SMR) and incidence (SIR) ratios by district in France, pooling 30 and 10 years of data, respectively. Using correlation coefficients, we compared geographical patterns of male and female mesothelioma ratios, and IAE and no IAE mesothelioma ratios.

RESULTS: The raw numbers of male and female mesothelioma cases were equivalent. Mesothelioma SMR (0.76) and SIR (0.80) geographical correlations between men and women were strongly positive. SIR correlation between occupationally IAE and no IAE cases was also positive (0.69). Correlation between occupationally IAE and no IAE cases was positive among women but not among men.

CONCLUSIONS: Data analyses of mesothelioma mortality and incidence showed that female cases occur in the same geographical areas as male cases. Female mesotheliomas with no IAE occur in the same geographical areas as exposed cases, suggesting asbestos has a major influence on female mesothelioma, likely through environmental exposure.}, } @article {pmid20522518, year = {2010}, author = {Finkelstein, MM and Meisenkothen, C}, title = {Malignant mesothelioma among employees of a Connecticut factory that manufactured friction materials using chrysotile asbestos.}, journal = {The Annals of occupational hygiene}, volume = {54}, number = {6}, pages = {692-696}, doi = {10.1093/annhyg/meq046}, pmid = {20522518}, issn = {1475-3162}, mesh = {Aged ; Air Pollutants, Occupational/*analysis ; Asbestos, Serpentine/*analysis ; Connecticut/epidemiology ; Fatal Outcome ; Female ; Humans ; Male ; *Manufactured Materials ; Mesothelioma/*mortality ; Occupational Exposure/*adverse effects/statistics & numerical data ; Quebec/epidemiology ; Risk Assessment ; }, abstract = {There is ongoing argument about the potency of chrysotile asbestos to cause malignant mesothelioma. Risk assessment for chrysotile is influenced by the alleged absence of mesotheliomas among workers at the Raybestos Manhattan friction products plant in Connecticut, a plant that essentially used only chrysotile asbestos. Regrettably, the statement that there is an absence of mesothelioma deaths in the Connecticut plant is false. In this paper, we report on our review of the work histories and pathological reports of five individuals from the Connecticut plant who were diagnosed with mesothelioma. We discuss the Connecticut plant in relation to the most recent epidemiological information for chrysotile. Calculation suggests that mesothelioma rates at this plant were similar to those observed among Quebec miners and the South Carolina textile plant. We urge everyone concerned with the risk assessment of chrysotile asbestos to make use of all available data.}, } @article {pmid20521566, year = {2010}, author = {Marinaccio, A}, title = {[Scientific research, epidemiologic surveillance, and compensation criteria for asbestos-related diseases].}, journal = {La Medicina del lavoro}, volume = {101}, number = {2}, pages = {146-148}, pmid = {20521566}, issn = {0025-7818}, mesh = {Academies and Institutes/statistics & numerical data ; Asbestos/*adverse effects ; Female ; Humans ; Incidence ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology/etiology ; Occupational Diseases/*epidemiology/etiology ; *Population Surveillance ; Workers' Compensation/*statistics & numerical data ; }, } @article {pmid20521020, year = {2010}, author = {Hieckel, HG and Hering, KG}, title = {[Asbestos-related diseases of the thorax].}, journal = {Der Radiologe}, volume = {50}, number = {7}, pages = {623-33; quiz 634}, pmid = {20521020}, issn = {1432-2102}, mesh = {Asbestosis/*diagnosis ; Carcinoma, Bronchogenic/*diagnosis ; Expert Testimony/legislation & jurisprudence ; Germany ; Humans ; Image Processing, Computer-Assisted ; Lung Neoplasms/*diagnosis ; Mesothelioma/*diagnosis ; Occupational Exposure/adverse effects/legislation & jurisprudence ; Pleural Neoplasms/*diagnosis ; Pleurisy/*diagnosis ; Tomography, X-Ray Computed ; Workers' Compensation/legislation & jurisprudence ; }, abstract = {Asbestos fibers can lead to pulmonary fibrosis, thickening of the pleura and malignancies. These pathologic changes are possible rather than determinate and depend on the type of asbestos fiber, length of exposure to fibers and individual factors. In Germany asbestos fibers were widely used until 1993. Worldwide, there is currently no general ban on the use of asbestos. The leading cause of asbestos-related diseases is occupational exposure. Due to a long latency period the appearance of such diseases may be delayed for more than 40 years so that the final number of cases has not yet been reached. Occupationally-derived asbestos-related diseases of the thorax are asbestosis, asbestos-related benign pleurisy and malignant pleural mesothelioma. Bronchial carcinoma can also be caused by asbestos exposure. For proof of occupational exposure, radiologists are required to report the presence of characteristic findings. The detection, in particular by chest X-ray and high resolution computed tomography (HRCT), requires high quality images and standardized evaluation. The standardized ILO classification and the semi-quantitative HRCT coding are medical findings on which statutory registration criteria are based.}, } @article {pmid22933897, year = {2010}, author = {Podobnik, J and Kocijancic, I and Kovac, V and Sersa, I}, title = {3T MRI in evaluation of asbestos-related thoracic diseases - preliminary results.}, journal = {Radiology and oncology}, volume = {44}, number = {2}, pages = {92-96}, pmid = {22933897}, issn = {1318-2099}, abstract = {BACKGROUND: 3T high-field magnetic resonance imaging (MRI) scanners have recently become available for the clinical use and are being increasingly applied in the field of whole-body imaging and chest imaging as well. The aim of this study was to evaluate the diagnostic potential of 3 T MRI as a complementary imaging modality to CT in detecting the pathological changes of asbestos-related thoracic diseases.

PATIENTS AND METHODS: Fifteen patients with the asbestos-related thoracic disease were scheduled for 3T MRI. Five had a benign form of the disease and 10 had malignant pleural mesothelioma (MPM). From the patients with a benign form of the disease their last CT examination in digital form was acquired and patients with MPM were scheduled for CT examination with contrast media. The protocol of MR imaging consists of T2-weighted cardiac-gated breath-hold turbo spin echo (TSE) sequences in coronal, sagittal and axial plane and T1-weighted cardiac-gated breath-hold TSE black blood in axial plane. In T2-weighted sequences in axial plane, fat saturation was also used. CT examinations were obtained with the administration of the contrast medium from lung apices to the lower end of the liver. Images of 5 mm (mediastinum window) and 3 mm (lung window) in axial plan were reconstructed. MRI signal intensity of lesions and adjacent muscles on Syngo MultiModality Work Place were measured.

RESULTS: Compared to muscles pleural plaques appeared hypo-intense to iso-intense on T1 weighted images (in 100%) and also hypo-intense on T2 fs-weighted images (in 100%). MPM appeared inhomogeneous hypo-intense to iso-intense on T1-weighted and hyperintense on T2 fs-weighted images in all patients (100%).

CONCLUSIONS: These preliminary results pointed out that MRI was equal or even better compared with CT examination for detecting possible malignant potential of pleural changes in the asbestos-related pleural disease, using signal intensity measurements of T2 fs-weighted images. The 3T MRI enabled the accurate determination of chest pathology and it could be used for imaging of patients with the asbestos-related thoracic disease. MRI is particularly valuable because a patient is not exposed to the harmful radiation which is important if imaging methods are used repeatedly, like in screening programs or in monitoring of treatment results. This finding turned us to propose 3T MRI imaging technique as a non-ionizing imaging method for the follow-up of patients with the isolated pleural form of the asbestos-related disease.}, } @article {pmid20509881, year = {2010}, author = {Raiko, I and Sander, I and Weber, DG and Raulf-Heimsoth, M and Gillissen, A and Kollmeier, J and Scherpereel, A and Brüning, T and Johnen, G}, title = {Development of an enzyme-linked immunosorbent assay for the detection of human calretinin in plasma and serum of mesothelioma patients.}, journal = {BMC cancer}, volume = {10}, number = {}, pages = {242}, pmid = {20509881}, issn = {1471-2407}, mesh = {Adult ; Aged ; Antibody Specificity ; Anticoagulants/chemistry ; Asbestos/adverse effects ; Biomarkers, Tumor/*blood ; Calbindin 2 ; Calcium Chloride/chemistry ; Chelating Agents/chemistry ; Construction Materials/adverse effects ; Edetic Acid/chemistry ; *Enzyme-Linked Immunosorbent Assay ; Female ; Heparin/chemistry ; Humans ; Male ; Mesothelioma/*blood/etiology/pathology ; Middle Aged ; Occupational Exposure ; Predictive Value of Tests ; Protein Stability ; S100 Calcium Binding Protein G/*blood ; Sensitivity and Specificity ; Specimen Handling/methods ; }, abstract = {BACKGROUND: Calretinin is one of the well-established immunohistochemical markers in the diagnostics of malignant mesothelioma (MM). Its utility as a diagnostic tool in human blood, however, is scarcely investigated. The aim of this study was to develop an enzyme-linked immunosorbent assay (ELISA) for human calretinin in blood and to assess its usefulness as a potential minimally invasive diagnostic marker for MM.

METHODS: Initially, attempts were made to establish an assay using commercially available antibodies and to optimize it by including a biotin-streptavidin complex into the assay protocol. Subsequently, a novel ELISA based on polyclonal antibodies raised in rabbit immunized with human recombinant calretinin was developed. The assay performance in human serum and plasma (EDTA/heparin) and the influence of calcium concentrations on antibody recognition were studied. Stability of spiked-in calretinin in EDTA plasma under different storage conditions was also examined. In preliminary studies serum and plasma samples from 97 healthy volunteers, 35 asbestos-exposed workers, and 42 MM patients were analyzed.

RESULTS: The mean detection range of the new ELISA was 0.12 to 8.97 ng/ml calretinin. The assay demonstrated markedly lower background and significantly higher sensitivity compared to the initially contrived assay that used commercial antibodies. Recovery rate experiments confirmed dependence of calretinin antibody recognition on calcium concentration. Calcium adjustment is necessary for calretinin measurement in EDTA plasma. Spiked-in calretinin revealed high stability in EDTA plasma when stored at room temperature, 4 degrees C, or after repeated freeze/thaw cycles. Median calretinin values in healthy volunteers, asbestos workers, and MM patients were 0.20, 0.33, and 0.84 ng/ml, respectively (p < 0.0001 for healthy vs. MM, p = 0.0036 for healthy vs. asbestos-exposed, p < 0.0001 for asbestos-exposed vs. MM). Median values in patients with epithelioid and biphasic MM were similar. No influence of age, gender, smoking status, or type of medium (plasma/serum) on calretinin values was found.

CONCLUSIONS: The novel assay is highly sensitive and applicable to human serum and plasma. Calretinin appears to be a promising marker for the blood-based detection of MM and might complement other markers. However, further studies are required to prove its usefulness in the diagnosis of MM patients.}, } @article {pmid20497872, year = {2010}, author = {Mensi, C and Garberi, A and Sieno, C and Riboldi, L}, title = {Porcelain factory worker with asbestos-related mesothelioma.}, journal = {Journal of the Formosan Medical Association = Taiwan yi zhi}, volume = {109}, number = {5}, pages = {389}, doi = {10.1016/S0929-6646(10)60067-8}, pmid = {20497872}, issn = {0929-6646}, mesh = {Asbestos/*adverse effects ; Dental Porcelain ; Humans ; Italy/epidemiology ; Male ; Manufactured Materials ; Mesothelioma/*epidemiology/etiology ; Occupational Exposure ; Pleural Neoplasms/*epidemiology/etiology ; Registries ; }, } @article {pmid20490468, year = {2010}, author = {Yao, S and DellaVentura, G and Petibois, C}, title = {Analytical characterization of cell-asbestos fiber interactions in lung pathogenesis.}, journal = {Analytical and bioanalytical chemistry}, volume = {397}, number = {6}, pages = {2079-2089}, doi = {10.1007/s00216-010-3773-x}, pmid = {20490468}, issn = {1618-2650}, mesh = {Asbestos/adverse effects/chemistry ; Chemistry Techniques, Analytical/*methods ; Cytological Techniques ; Histological Techniques ; Humans ; Lung Diseases/*etiology/pathology ; Microscopy ; }, abstract = {Asbestos is a fiber causing lung diseases such as asbestosis and mesothelioma. Although the process involving these diseases remains to be elucidated for developing drugs and treatments, direct consequences of fiber exposure in humans have been clearly demonstrated. These diseases are first characterized by histological heterogeneity and combine chronic inflammation with fibrosis and cellular alterations. As a consequence, asbestosis is usually diagnosed at advanced stages of the disease and treatments are usually inefficient to cure the patients. Here, we review the links established between asbestos fiber chemistry and morphology with the occurrence of associated lung diseases. Cytological and histological aspects of diseases are described with respect to current analytical capabilities, notably for microscopy techniques.}, } @article {pmid20490323, year = {2010}, author = {Jiang, L and Yamashita, Y and Toyokuni, S}, title = {A novel method for efficient collection of normal mesothelial cells in vivo.}, journal = {Journal of clinical biochemistry and nutrition}, volume = {46}, number = {3}, pages = {265-268}, pmid = {20490323}, issn = {1880-5086}, abstract = {Asbestos-induced mesothelioma is a challenging social problem in many countries, and oxidative stress via iron is closely associated with its carcinogenesis. Mesothelioma is thought to originate from the mesothelial cells that cover the somatic cavity such as pleural, pericardial and peritoneal cavities. They are single layered and so flat that it is extremely difficult to obtain pure mesothelial cells as control samples from experimental animals. Here we describe a novel method to collect mesothelial cells from animals by the use of simple equipments. Surface of the most organs including lung, spleen and liver are covered with a single layer of mesothelial cells. Scraping the surface of those organs with razor blades after snap-freeze in liquid nitrogen satisfactorily confers almost pure population of mesothelial cells. This simple method would be helpful for obtaining mesothelial control samples from animals to elucidate the molecular mechanisms of a variety of mesothelial pathology.}, } @article {pmid20448500, year = {2010}, author = {Berrill, J and Haboubi, H and Duane, P}, title = {Peritoneal mesothelioma.}, journal = {British journal of hospital medicine (London, England : 2005)}, volume = {71}, number = {5}, pages = {290-291}, doi = {10.12968/hmed.2010.71.5.47912}, pmid = {20448500}, issn = {1750-8460}, mesh = {Asbestos/*adverse effects ; Ascites/etiology ; Humans ; Male ; Mesothelioma/*diagnosis/drug therapy ; Middle Aged ; Mineral Fibers/adverse effects ; Peritoneal Neoplasms/*diagnosis/drug therapy ; Tomography, X-Ray Computed ; }, abstract = {Peritoneal disease accounts for just under a third of all malignant mesothelioma. Its insidious onset means that diagnosis is often made at an advanced stage, however, new therapeutic techniques are starting to lead to improved outcomes.}, } @article {pmid20445731, year = {2010}, author = {Torrejón Reyes, PN and Frisancho, O and Gómez, A and Yábar, A}, title = {[Malignant peritoneal mesothelioma].}, journal = {Revista de gastroenterologia del Peru : organo oficial de la Sociedad de Gastroenterologia del Peru}, volume = {30}, number = {1}, pages = {82-87}, pmid = {20445731}, issn = {1022-5129}, mesh = {Humans ; Male ; *Mesothelioma/diagnosis ; Middle Aged ; *Peritoneal Neoplasms/diagnosis ; }, abstract = {The peritoneal mesothelioma is a rare pathology with unspecific symptoms reason to be a difficult diagnosis. We report a case of a 58 year old man with diabetes mellitus type 2, arterial hypertension and smoking; without precedent of asbestos exposure. The patient presented a one month history characterized by progressive increase of the abdominal volume and sensation of fullness; three weeks later they added breathlessness and hyporexia. The patient was in regular general condition; he was not presenting hepatic stigmas, edema or adenomegalies. The examination of thorax and cardiovascular it was normal. The abdomen distended by ascites, not painful, liver and spleen not examined. Laboratory: Hemoglobin 11,9 gr/dl, WBC 6840/mm3 Bands 1 %, lymphocytes 10 %, platelets 620000/mm3, PT 12 seconds, PTT 34 seconds, glucose 158 mg/dl, BUN 20,5 mg/ dl, creatinine 1,2 mg/dl, proteins 6,1 gr/dl, albumin 2,6 gr/dl. LDH 316 U/l, beta2microglobulin 2,2 mg/l (0.83-1.15 mg/l). HBV and HCV negative. Ca 19.9, CEA, AFP and PSA negative. Hemocultive negative. Ascitic fluid: ADA 20,3 U/l, serum-ascitic albumin gradient (SAAG) 1,1. Leukocytes 2237 cells/mm3, PMN 6 %, lymphocytes 90 %, mesothelial cells 4 %, proteins 4,6 gr/dl, albumin 2,34 gr/dl, glucose 44 mg/dl, LDH 1918 U/l. Gram and cultive: negatives. BAAR and cultive: negative . Cytology: mesothelial cells with changes of type reagent, Block cell for tumour cells: negative. Abdominal US: increased peritoneum and abundant ascitic fluid. Thoracic-abdominal CT: left side pleural effusion, severe ascites with thick epyplon. Upper GI endoscopy: moderate gastritis. Colonoscopy: two small sessile polyps in sigmoid colon. The finds of the laparoscopy were interpreted like carcinomatosis or peritoneal tuberculosis. The report of the peritoneal biopsy was informed as suggestive of undifferentiated carcinoma; the reappraisal with inmunohystochemic (calretinin +,cytokeratin +, vimentin +) indicated malignant peritoneal mesothelioma, type epithelial. The evolution was torpid. The patient was transferred to the Service of Oncology where they initiated chemotherapy with Cysplatin (CDDP) and died 20 days later. The malignant mesothelioma peritoneal is a unfrequent entity, with limited therapeutic options; generally detected late, with a palliative treatment.}, } @article {pmid20440397, year = {2009}, author = {Rao, S}, title = {Malignant pleural mesothelioma.}, journal = {Lung India : official organ of Indian Chest Society}, volume = {26}, number = {2}, pages = {53-54}, pmid = {20440397}, issn = {0974-598X}, abstract = {Malignant mesothelioma is one of the rare tumors of pleura. One such case in a 57-year-old male, who presented with hemorrhagic pleural effusion and had no history of asbestos exposure, is reported here. The rarity, unusual presentation, and implications are discussed.}, } @article {pmid20439227, year = {2010}, author = {Metintas, M and Hillerdal, G and Metintas, S and Dumortier, P}, title = {Endemic malignant mesothelioma: exposure to erionite is more important than genetic factors.}, journal = {Archives of environmental & occupational health}, volume = {65}, number = {2}, pages = {86-93}, doi = {10.1080/19338240903390305}, pmid = {20439227}, issn = {2154-4700}, mesh = {Adult ; Aged ; Aged, 80 and over ; Construction Materials/adverse effects ; Emigration and Immigration/statistics & numerical data ; Environmental Exposure/*adverse effects/statistics & numerical data ; Female ; Humans ; Male ; Mesothelioma/*chemically induced/epidemiology/etiology/genetics ; Middle Aged ; Prevalence ; Time Factors ; Turkey/epidemiology ; Young Adult ; Zeolites/*poisoning ; }, abstract = {The village of Karain, Turkey, has the world's highest prevalence rate of malignant mesothelioma (MM). Environmental exposure to erionite is thought to cause the disease. However, it has also been suggested that the disease is mainly genetic. Residents in Karain village were traced from 1990 to 2006. Mineral samples were obtained from stones used in construction of their houses and any fibers present were identified. All women who had moved to the village as brides were traced and their cause of death determined. MM was the cause of death in 52 of 322 villagers, representing 50.5% of all deaths. Only 2 of 8 types of stones used in construction contained erionite, and these stones had been used almost exclusively in the mid-sections of the village, where MM was common. In houses not containing erionite, no cases of MM were observed. Sixty-four women came as brides to Karain from villages where erionite or asbestos is not found. Of the 16 women who have died, 11 (69%) died from MM. The extreme risk of MM in Karain is due to indoor exposure to erionite. The effect of genetic factors on mesothelioma development cannot be evaluated in this study, but is likely to be minor.}, } @article {pmid20431408, year = {2010}, author = {Larson, TC and Antao, VC and Bove, FJ}, title = {Vermiculite worker mortality: estimated effects of occupational exposure to Libby amphibole.}, journal = {Journal of occupational and environmental medicine}, volume = {52}, number = {5}, pages = {555-560}, doi = {10.1097/JOM.0b013e3181dc6d45}, pmid = {20431408}, issn = {1536-5948}, mesh = {Aged ; *Aluminum Silicates ; Asbestos, Amphibole/*adverse effects ; Cohort Studies ; Dose-Response Relationship, Drug ; Humans ; Middle Aged ; Montana/epidemiology ; Mortality/*trends ; Occupational Exposure/*adverse effects ; Proportional Hazards Models ; Retrospective Studies ; }, abstract = {OBJECTIVE: To examine the relationship between cumulative fiber exposure (CFE) and mortality in a retrospective cohort study of vermiculite workers exposed to Libby amphibole (n = 1862).

METHODS: Extended Cox regression was used to estimate the hazards associated with CFE as a time-dependent covariate of multiple-cause mortality.

RESULTS: The Cox models for mesothelioma, asbestosis, lung cancer, and non-malignant respiratory disease were significant with rate ratios that increased monotonically with CFE. The model for deaths due to cardiovascular disease was also significant (rate ratio for CFE > or =44.0 f/cc-y vs <1.4 f/cc-y was 1.5; 95% confidence interval = 1.1 to 2.0).

CONCLUSIONS: By using a within-cohort comparison, the results demonstrate a clear exposure-response relationship between CFE and mortality from asbestos-related causes. The finding of an association between CFE and cardiovascular mortality suggests persons exposed to Libby amphibole should be monitored for this outcome.}, } @article {pmid20431404, year = {2010}, author = {Ramazzini, C}, title = {Asbestos is still with us: repeat call for a universal ban.}, journal = {Journal of occupational and environmental medicine}, volume = {52}, number = {5}, pages = {469-472}, doi = {10.1097/JOM.0b013e3181ddf5ef}, pmid = {20431404}, issn = {1536-5948}, mesh = {Aged ; Asbestos/*adverse effects/poisoning ; Environmental Exposure ; Female ; Global Health ; Humans ; *International Cooperation ; Male ; Mesothelioma/mortality ; Neoplasms/epidemiology/etiology/mortality ; Occupational Exposure/prevention & control ; United Nations ; }, } @article {pmid20427324, year = {2010}, author = {Phillips, JI and Murray, J}, title = {Malignant mesothelioma in a patient with anthophyllite asbestos fibres in the lungs.}, journal = {The Annals of occupational hygiene}, volume = {54}, number = {4}, pages = {412-416}, doi = {10.1093/annhyg/meq034}, pmid = {20427324}, issn = {1475-3162}, mesh = {Aged ; Animals ; Asbestos, Amphibole/analysis/*toxicity ; Autopsy ; Fatal Outcome ; Humans ; Industry ; Male ; Mesothelioma/chemically induced/*diagnosis ; Microscopy, Electron, Transmission ; Mineral Fibers/analysis/toxicity ; Occupational Diseases/chemically induced/*diagnosis ; Occupational Exposure/analysis/statistics & numerical data ; Plastics ; Pleural Neoplasms/chemically induced/*diagnosis ; South Africa ; Talc/chemistry/toxicity ; }, abstract = {The amphibole asbestos, anthophyllite, is associated with asbestos-related disease in humans, along with mesothelioma in animal models. In humans, however, there are only three cases of histologically proven malignant mesothelioma of the pleura associated with anthophyllite that have been documented in the English-language literature. A fourth case is presented in a man who lived in South Africa and had anthophyllite in his lung. Anthophyllite was never commercially mined in South Africa. Using scanning electron microscopy, his lung fibre burden was calculated to be 358,000 fibres and 31,000 asbestos bodies per gram of dry weight of lung tissue. The mean aspect ratio of the anthophyllite fibres in the lung was 41.2 (SD = 28.8). No other types of asbestos were detected in the lung. His exposure was almost certainly occupational. He worked in the plastic manufacturing industry and was exposed to talc and asbestos blankets that were used to insulate machinery.}, } @article {pmid20424618, year = {2010}, author = {Rushton, L and Bagga, S and Bevan, R and Brown, TP and Cherrie, JW and Holmes, P and Fortunato, L and Slack, R and Van Tongeren, M and Young, C and Hutchings, SJ}, title = {Occupation and cancer in Britain.}, journal = {British journal of cancer}, volume = {102}, number = {9}, pages = {1428-1437}, pmid = {20424618}, issn = {1532-1827}, mesh = {Agricultural Workers' Diseases/epidemiology ; Asbestos ; Carcinogens ; Coal Tar/adverse effects ; Female ; Humans ; Incidence ; Industry ; Male ; Mesothelioma/chemically induced ; Neoplasms/*epidemiology ; Occupational Diseases/*epidemiology ; Occupational Exposure/*adverse effects ; Occupations/*statistics & numerical data ; United Kingdom/epidemiology ; }, abstract = {BACKGROUND: Prioritising control measures for occupationally related cancers should be evidence based. We estimated the current burden of cancer in Britain attributable to past occupational exposures for International Agency for Research on Cancer (IARC) group 1 (established) and 2A (probable) carcinogens.

METHODS: We calculated attributable fractions and numbers for cancer mortality and incidence using risk estimates from the literature and national data sources to estimate proportions exposed.

RESULTS: 5.3% (8019) cancer deaths were attributable to occupation in 2005 (men, 8.2% (6362); women, 2.3% (1657)). Attributable incidence estimates are 13 679 (4.0%) cancer registrations (men, 10 063 (5.7%); women, 3616 (2.2%)). Occupational attributable fractions are over 2% for mesothelioma, sinonasal, lung, nasopharynx, breast, non-melanoma skin cancer, bladder, oesophagus, soft tissue sarcoma, larynx and stomach cancers. Asbestos, shift work, mineral oils, solar radiation, silica, diesel engine exhaust, coal tars and pitches, occupation as a painter or welder, dioxins, environmental tobacco smoke, radon, tetrachloroethylene, arsenic and strong inorganic mists each contribute 100 or more registrations. Industries and occupations with high cancer registrations include construction, metal working, personal and household services, mining, land transport, printing/publishing, retail/hotels/restaurants, public administration/defence, farming and several manufacturing sectors. 56% of cancer registrations in men are attributable to work in the construction industry (mainly mesotheliomas, lung, stomach, bladder and non-melanoma skin cancers) and 54% of cancer registrations in women are attributable to shift work (breast cancer).

CONCLUSION: This project is the first to quantify in detail the burden of cancer and mortality due to occupation specifically for Britain. It highlights the impact of occupational exposures, together with the occupational circumstances and industrial areas where exposures to carcinogenic agents occurred in the past, on population cancer morbidity and mortality; this can be compared with the impact of other causes of cancer. Risk reduction strategies should focus on those workplaces where such exposures are still occurring.}, } @article {pmid20414089, year = {2011}, author = {Pinto, C and Ardizzoni, A and Betta, PG and Facciolo, F and Tassi, G and Tonoli, S and Zompatori, M and Alessandrini, G and Magrini, SM and Tiseo, M and Mutri, V}, title = {Expert opinions of the first italian consensus conference on the management of malignant pleural mesothelioma.}, journal = {American journal of clinical oncology}, volume = {34}, number = {1}, pages = {99-109}, doi = {10.1097/COC.0b013e3181d31f02}, pmid = {20414089}, issn = {1537-453X}, mesh = {Chemotherapy, Adjuvant ; Female ; Humans ; Italy ; Laparoscopy ; Male ; Mesothelioma/*diagnosis/therapy ; Pleural Neoplasms/*diagnosis/*therapy ; Practice Guidelines as Topic ; Radiotherapy, Adjuvant ; Respiratory Function Tests ; Thoracic Surgical Procedures ; Thoracoscopy ; }, abstract = {Malignant pleural mesothelioma (MPM) is a very important public health issue. A large amount of data indicates a relationship between mesothelioma and asbestos exposure. The incidence has both considerably and constantly increased over the past 2 decades in the industrialized countries and is expected to peak in 2010-2020. In Italy, a standardized-rate incidence in 2002 among men was 2.98 per 100,000 and 0.98 per 100,000 among women, with wide differences from one region to another. Stage diagnosis and definition may be difficult. Management of patients with MPM remains complex, so an optimal treatment strategy has not yet been clearly defined. The First Italian Consensus Conference on Malignant Pleural Mesothelioma was held Bologna (Italy) in May 20, 2008. The Consensus Conference was given the patronage of the Italian scientific societies AIOM, AIRO, AIPO, SIC, SICO, SICT, SIAPEC-IAP, AIOT, GOAM, and GIME. This Consensus did not answer all of the unresolved questions in MPM management, but the Expert Opinions have nonetheless provided recommendations, presented in this report, on MPM management for clinicians and patients.}, } @article {pmid20412567, year = {2010}, author = {Rosell-Murphy, M and Abós-Herràndiz, R and Tarrés, J and Martínez-Artés, X and García-Allas, I and Krier, I and Cantarell, G and Gallego, M and Orriols, R and Albertí, C}, title = {Prospective study of asbestos-related diseases incidence cases in primary health care in an area of Barcelona province.}, journal = {BMC public health}, volume = {10}, number = {}, pages = {203}, pmid = {20412567}, issn = {1471-2458}, mesh = {Adult ; Asbestosis/*epidemiology/mortality ; Cluster Analysis ; Female ; Humans ; Incidence ; Male ; Population Surveillance ; Primary Health Care ; Prospective Studies ; Spain/epidemiology ; }, abstract = {BACKGROUND: Asbestos related diseases include a number of conditions due to inhalation of asbestos fibres at work, at home or in the environment, such as pleural mesothelioma, asbestosis and calcified pleural plaques. Few epidemiological studies have established the incidence of asbestos related diseases in our area. The present proposal is based on a retrospective study externally funded in 2005 that is currently taking place in the same area and largely carried out by the same research team.The aim of the study is to achieve a comprehensive and coordinated detection of all new cases of Asbestos Related Diseases presenting to primary care practitioners.

METHODS/DESIGN: This is a multicentre, multidisciplinary and pluri-institutional prospective study.Setting12 municipalities in the Barcelona province within the catchment area of the health facilities that participate in the study.SampleThis is a population based study, of all patients presenting with diseases caused by asbestos in the study area.MeasurementsA clinical and epidemiological questionnaire will be filled in by the trained researchers after interviewing the patients and examining their clinical reports.

DISCUSSION: Data on the incidence of the different Asbestos Related Diseases in this area will be obtained and the most plausible exposure source and space-time-patient profile will be described. The study will also improve the standardization of patient management, the coordination between health care institutions and the development of preventive activities related with asbestos exposure and disease.}, } @article {pmid20400397, year = {2010}, author = {Németh, T and Furák, J and Wolfárd, A and Géczi, T and Tiszlavicz, L and Lázár, G}, title = {[Surgical treatment of primary pleural tumours in our department].}, journal = {Magyar sebeszet}, volume = {63}, number = {2}, pages = {67-74}, doi = {10.1556/MaSeb.63.2010.2.3}, pmid = {20400397}, issn = {0025-0295}, mesh = {Aged ; Biopsy ; Carcinoma/surgery ; Female ; Humans ; Hungary ; Male ; Mesothelioma/surgery ; Middle Aged ; Neoplasm Staging ; Pleural Neoplasms/diagnostic imaging/pathology/*surgery ; Pleurodesis ; Pneumonectomy ; Retrospective Studies ; Sarcoma/surgery ; Thoracic Surgery, Video-Assisted ; Tomography, X-Ray Computed ; Treatment Outcome ; }, abstract = {AIM: The authors analyzed the results and outcome of surgical treatment of primary pleural tumors in patients treated in the last 11 years.

METHODS: 31 operations were performed for primary pleural tumors in 25 patients (17 males, 8 females). The tumors were classified into the following groups: benign local fibrous tumors (benign LFTP; n = 15), recurrent malignant fibrous tumors (recurrent malignant LFTP; n = 2) and malignant mesotheliomas (MPM; n = 12). 40% of patients with MPM were exposed to asbestos. Complete resections of benign LFTPs were performed, with additional resection of the chest wall and lobectomy in two cases. Completion pneumonectomy and lobectomy were done in recurrent malignant LFTP cases. Five biopsies and pleurodesis, and one open decortication were performed. In four cases, after the biopsy, two pleurectomies and decortications (P/D) and two pleuropneumonectomies (PPN)/extra-pleural pneumonectomies (EPP) were carried out.

RESULTS: There was no operative mortality. Pathological examination revealed seven epithelial, two sarcomatous and one biphasic malignant mesotheliomas. Survival was one (currently alive) and 49 months after malignant recurrent LFTP. Survival in MPM cases was 9,7 months (3-17) without resection and 17,3 months (5 (currently alive) - 29) in P/D or PPN (EPP) cases.

CONCLUSIONS: The PPN (EPP) and P/D are safe procedures providing relatively good survival when it is done as part of complete oncological treatment. In cases of recurrent LFTP, anatomical resections recommended with completion pneumonectomy or lobectomy.}, } @article {pmid20388033, year = {2010}, author = {Utell, MJ and Maxim, LD}, title = {Refractory ceramic fiber (RCF) toxicity and epidemiology: a review.}, journal = {Inhalation toxicology}, volume = {22}, number = {6}, pages = {500-521}, doi = {10.3109/08958370903521224}, pmid = {20388033}, issn = {1091-7691}, mesh = {Animals ; Ceramics/chemistry/*toxicity ; Humans ; Mineral Fibers/*toxicity ; *Occupational Exposure/adverse effects/analysis ; Respiratory Function Tests ; Respiratory Tract Diseases/*epidemiology/*etiology ; Toxicity Tests ; }, abstract = {This paper provides a review of the relevant literature on refractory ceramic fibers (RCFs), summarizing relevant data and information on the manufacture, processing, applications, potential occupational exposure, toxicology, epidemiology, risk analysis, and risk management. RCFs are amorphous fibers used for high-temperature insulation applications. RCFs are less durable/biopersistent than amphibole asbestos, but more durable/biopersistent than many other synthetic vitreous fibers (SVFs). Moreover, as produced/used, some RCFs are respirable. Toxicology studies with rodents using various exposure methods have shown that RCFs can cause fibrosis, lung cancer, and mesothelioma. Interpretation of these animal studies is difficult for various reasons (e.g., overload in chronic inhalation bioassays). Epidemiological studies of occupationally exposed cohorts in Europe and the United States have demonstrated measurable effects (e.g., mild respiratory symptoms and pleural plaques) but no disease (i.e., no interstitial fibrosis, no excess lung cancer, and no mesothelioma) to date. The RCF industry, working cooperatively with various government agencies in the United States, has developed a comprehensive product stewardship program (PSP) to identify and control risks associated with occupational exposure. One provision of the PSP is the adoption of a voluntary recommended exposure guideline (REG) of 0.5 fibers/milliliter (f/ml). Selected on the basis of prudence and demonstrated feasibility, compliance with the REG should reduce risks to levels between 0.073/1000 and 1.2/1000, based on extrapolations from chronic animal inhalation studies.}, } @article {pmid20386624, year = {2009}, author = {Bianchi, C and Bianchi, T}, title = {Malignant pleural mesothelioma in Italy.}, journal = {Indian journal of occupational and environmental medicine}, volume = {13}, number = {2}, pages = {80-83}, pmid = {20386624}, issn = {1998-3670}, abstract = {This study reviews a series of 811 malignant pleural mesothelioma cases, diagnosed at hospitals in Trieste and Monfalcone districts of north eastern Italy, a narrow coastal strip with a population of about three lakh, in the period 1968-2008. The diagnosis was based on histological examination in 801 cases, and cytological findings in 10. Necropsy was performed in 610 cases. Occupational histories were obtained directly from the patients or their relatives through personal or telephone interviews. Routine lung sections were examined for asbestos bodies in 500 cases. In 143 cases asbestos bodies were isolated and counted by chemical digestion of the lung tissue using the Smith-Naylor method. The series included 717 men and 94 women aged between 32 and 93 years (mean 69.2 years). Detailed occupational data was obtained for 732 cases.The majority of patients had marine jobs - shipbuilding (449 cases), maritime trades (56 cases), and port activities (39 cases). The nature of work of other patients included a variety of occupations, with non-shipbuilding industries being the most common. Thirty-four women cleaned the work clothes of family members occupationally exposed and hence had a history of asbestos exposure at home. Most of the patients had their first exposure to asbestos before 1960. The latency period ranged between 13 and 73 years (mean 48.2). Latency period among insulators and dock workers were shorter than other categories. Asbestos bodies were detected on routine lung sections in 343 cases (68.6%). Lung asbestos body burdens after isolation ranged between two to 10 millions bodies per gram of dried tissue. Despite some limitations in the use of asbestos in this area since the 1970s, the incidence of tumor remained high during the last years.}, } @article {pmid20380827, year = {2010}, author = {Liu, G and Beri, R and Mueller, A and Kamp, DW}, title = {Molecular mechanisms of asbestos-induced lung epithelial cell apoptosis.}, journal = {Chemico-biological interactions}, volume = {188}, number = {2}, pages = {309-318}, doi = {10.1016/j.cbi.2010.03.047}, pmid = {20380827}, issn = {1872-7786}, mesh = {Animals ; Apoptosis ; Asbestos/*toxicity ; Asbestosis/*pathology ; Carcinogens/metabolism ; Epithelial Cells/*pathology ; Humans ; Lung/*pathology ; }, abstract = {Asbestos causes pulmonary fibrosis (asbestosis) and malignancies (bronchogenic lung cancer and mesothelioma) by mechanisms that are not fully elucidated. Accumulating evidence show that alveolar epithelial cell (AEC) apoptosis is a crucial initiating and perpetuating event in the development of pulmonary fibrosis following exposure to a wide variety of noxious stimuli, including asbestos. We review the important molecular mechanisms underlying asbestos-induced AEC apoptosis. Specifically, we focus on the role of asbestos in augmenting AEC apoptosis by the mitochondria- and p53-regulated death pathways that result from the production of iron-derived reactive oxygen species (ROS) and DNA damage. We summarize emerging evidence implicating the endoplasmic reticulum (ER) stress response in AEC apoptosis in patients with idiopathic pulmonary fibrosis (IPF), a disease with similarities to asbestosis. Finally, we discuss a recent finding that a mitochondrial oxidative DNA repair enzyme (8-oxoguanine DNA glycosylase; Ogg1) acts as a mitochondrial aconitase chaperone protein to prevent oxidant (asbestos and H(2)O(2))-induced AEC mitochondrial dysfunction and intrinsic apoptosis. The coupling of mitochondrial Ogg1 to mitochondrial aconitase is a novel mechanism linking metabolism to mitochondrial DNA that may be important in the pathophysiologic events resulting in oxidant-induced toxicity as seen in tumors, aging, and respiratory disorders (e.g. asbestosis, IPF). Collectively, these studies are illuminating the molecular basis of AEC apoptosis following asbestos exposure that may prove useful for developing novel therapeutic strategies. Importantly, the asbestos paradigm is elucidating pathophysiologic insights into other more common pulmonary diseases, such as IPF and lung cancer, for which better therapy is required.}, } @article {pmid20363987, year = {2010}, author = {Varga, C and Szendi, K}, title = {Carbon nanotubes induce granulomas but not mesotheliomas.}, journal = {In vivo (Athens, Greece)}, volume = {24}, number = {2}, pages = {153-156}, pmid = {20363987}, issn = {0258-851X}, mesh = {Animals ; Disease Models, Animal ; Disease Progression ; Granuloma/*chemically induced/epidemiology/pathology ; Mesothelioma/*chemically induced/epidemiology/pathology ; Nanotubes, Carbon/*toxicity ; Peritoneal Neoplasms/*chemically induced/epidemiology/pathology ; Rats ; Risk Assessment ; Risk Factors ; }, abstract = {BACKGROUND: Different types of carbon nanotubes may represent toxic hazards due to their size distribution and massive surface area. They may adsorb other toxic agents that can consequently be transported into the body. Hence the aim of this study was to confirm or reject the hypothesis of carcinogenicity of two types of carbon nanotubes.

MATERIALS AND METHODS: Well-defined single-walled and multi-walled carbon nanotubes were studied in a specific animal model for mesothelioma induction.

RESULTS: Short-term pilot studies were published on the asbestos fibre-like mesothelioma-inducing effects of carbon nanotubes based on the proposed mechanistic correlation on health effects of fibres of the same size. Our results with a simple in vivo, peritoneal exposure model refute such an interpretation. The present studies with rats indicate that early granuloma formation does not lead to the development of mesotheliomas during chronic exposure of peritoneal mesothelium to either single- or multi-walled carbon nanotubes of varied size.

CONCLUSION: Due to the limited toxicity data on carbon nanotubes, these results may be particularly important for risk assessment purposes.}, } @article {pmid20359562, year = {2010}, author = {Franke, M and Chung, HD and Johnson, FE}, title = {Squamous cell carcinoma arising from the pleura after pneumonectomy for squamous cell carcinoma of the lung.}, journal = {American journal of surgery}, volume = {199}, number = {4}, pages = {e34-5}, doi = {10.1016/j.amjsurg.2009.05.004}, pmid = {20359562}, issn = {1879-1883}, mesh = {Aged ; Bronchial Fistula/*complications/etiology ; Carcinoma, Bronchogenic/*surgery ; Carcinoma, Squamous Cell/secondary/*surgery ; Drainage ; Empyema/complications/etiology ; Fatal Outcome ; Humans ; Lung Neoplasms/*surgery ; Male ; Neoplasms, Second Primary/*diagnosis/etiology ; Palliative Care ; Pleural Diseases/complications/etiology ; Pleural Neoplasms/*diagnosis/etiology/pathology ; Pneumonectomy/*adverse effects ; Respiratory Tract Fistula/complications/etiology ; Spinal Neoplasms/secondary ; }, abstract = {BACKGROUND: A 67-year-old Caucasian man had a right pneumonectomy for primary bronchogenic carcinoma in 1998. He developed a bronchopleural fistula that was managed with an Eloesser procedure. His appearance 6 years later has been published previously.

METHODS: We performed a case report and literature search.

RESULTS: In 2008, the patient still had a bronchopleural fistula and reported a new symptom: constant right chest pain. He had experienced extensive asbestos exposure and mesothelioma was suspected. Endoscopy via the Eloesser aperture revealed innumerable tumor nodules. Biopsies of the pleura revealed multifocal, well-differentiated, squamous cell carcinoma with histology that was distinctly different from that of the original lung cancer. The tumor progressed rapidly during work-up and invaded the spine. He received palliative treatment but died 4 months after the onset of chest pain. We conducted a literature search and found 9 previous reports of epidermoid carcinoma arising from the pleura in patients with a chronically draining empyema; 5 patients had a prior pneumonectomy.

CONCLUSIONS: Cancer can arise in areas of chronic inflammation such as osteomyelitis with a draining sinus, Crohn's disease, or chronic gastritis. Cases of squamous cell carcinoma arising from the pleura in patients with a chronically draining empyema cavity are extremely rare. We believe this is the sixth report in the literature of squamous cell carcinoma arising from the pleura in a patient with a chronic postpneumonectomy bronchopleural fistula. In vivo video footage of the involved pleura is available}, } @article {pmid20357617, year = {2010}, author = {Yasumitsu, A and Tabata, C and Tabata, R and Hirayama, N and Murakami, A and Yamada, S and Terada, T and Iida, S and Tamura, K and Fukuoka, K and Kuribayashi, K and Nakano, T}, title = {Clinical significance of serum vascular endothelial growth factor in malignant pleural mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {5}, number = {4}, pages = {479-483}, doi = {10.1097/JTO.0b013e3181d2f008}, pmid = {20357617}, issn = {1556-1380}, mesh = {Aged ; Asbestos/adverse effects ; Asbestosis/*blood/pathology ; Biomarkers, Tumor/*blood ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Male ; Mesothelioma/*blood/pathology ; Neoplasm Staging ; Occupational Exposure ; Pleural Neoplasms/*blood/pathology ; Prognosis ; ROC Curve ; Survival Rate ; Vascular Endothelial Growth Factor A/*blood ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is an aggressive malignant tumor of mesothelial origin associated with asbestos exposure. MPM has a limited response to conventional chemotherapy and radiotherapy so diagnosing MPM early is very important. Vascular endothelial growth factor (VEGF) is an autocrine growth factor for MPM. Here, we investigated the serum levels of VEGF in patients with MPM in comparison with a population that had been exposed to asbestos without developing MPM.

METHODS: Serum concentrations of VEGF were measured in 51 patients with MPM and 42 individuals with benign asbestos-related diseases (asbestosis or pleural plaques) or who were healthy despite asbestos exposure.

RESULTS: We demonstrated that patients with MPM had significantly higher serum levels of VEGF than a population who had been exposed to asbestos but had not developed MPM, and the patients with advanced stage MPM showed higher levels of VEGF than the early stage patients with MPM. The difference in overall survival between the groups with VEGF serum levels lower and higher than the assumed cutoff of 460 pg/ml was significant.

CONCLUSIONS: Our data suggest that the VEGF serum concentration could be a useful marker for screening MPM among asbestos-exposed individuals and as a prognostic factor.}, } @article {pmid20347505, year = {2010}, author = {Gaafar, R and Bahnassy, A and Abdelsalam, I and Kamel, MM and Helal, A and Abdel-Hamid, A and Eldin, NA and Mokhtar, N}, title = {Tissue and serum EGFR as prognostic factors in malignant pleural mesothelioma.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {70}, number = {1}, pages = {43-50}, doi = {10.1016/j.lungcan.2010.01.002}, pmid = {20347505}, issn = {1872-8332}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*biosynthesis/blood ; Case-Control Studies ; ErbB Receptors/*biosynthesis/blood/genetics ; Female ; Gene Amplification ; Humans ; Male ; Mesothelioma/*enzymology/genetics/pathology ; Middle Aged ; Pleural Neoplasms/*enzymology/genetics/pathology ; Prognosis ; Prospective Studies ; Survival Analysis ; Young Adult ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is an asbestos related aggressive tumor. Asbestos causes genetic modifications and cell signaling events that favor resistance to chemotherapy. A variety of receptor tyrosine kinases have been identified to play a central role in various aspects of tumorigenesis. Epidermal growth factor receptor (EGFR) is overexpressed in a variety of epithelial malignancies including lung cancer in which EGFR aberrations not only predict response to EGFR tyrosine kinase inhibitors but also indicate tumor progression. However in MPM, the role of EGFR is less clear. This study was designed to identify serum and tissue EGFR levels in patients with MPM and to evaluate the relationship between serum and tissue EGFR levels and clinicao-pathological prognostic factors and survival.

METHODS: We investigated 71 cases of MPM for EGFR expression in tissue. Serum EGFR was assessed in 40 out of those 71 cases and 20 healthy subjects as a control. Pre-treatment serum EGFR levels were measured using quantitative enzyme-linked immunosorbent assay. Tissue EGFR protein overexpression was assessed by immunohistochemistry and gene amplification was assessed by the chromogen in situ hybridization (CISH) technique. Results were correlated with the clinical-pathological factors of the patients and overall survival (OS).

RESULTS: Out of the 71 patients included in the study, 19 had undergone extrapleural pneumonectomy. As for the rest of the patients, 46 received chemotherapy while 6 had only best supportive care. EGFR immuno-reactivity was detected in 74.6% of the cases, 37 (52.1%) cases were positive for EGFR gene amplification by CISH, 31 of them revealed moderate to high (++, +++) EGFR immuno-reactivity. Elevated serum EGFR >2.5 ng/ml (the median concentration of EGFR in MPM) was reported in 45% of the cases. The overall response rate (RR) for the 46 treated patients who received chemotherapy was 24.1%. After a median follow up of 29 months, the median overall survival (OS) was 10 months. Elevated serum and tissue EGFR is significantly associated with advanced disease stage. However neither EGFR overexpression in tissues nor high serum levels were associated with survival rates.

CONCLUSIONS: EGFR expression is a common feature in MPM patients. High pre-treatment levels of serum EGFR are associated with advanced stage but not with reduced OS. Detailed mutational analysis of EGFR on a larger number of patients is still needed to clarify the exact role of EGFR in MPM patients.}, } @article {pmid20345230, year = {2010}, author = {Park, EK and Thomas, PS and Creaney, J and Johnson, AR and Robinson, BW and Yates, DH}, title = {Factors affecting soluble mesothelin related protein levels in an asbestos-exposed population.}, journal = {Clinical chemistry and laboratory medicine}, volume = {48}, number = {6}, pages = {869-874}, doi = {10.1515/CCLM.2010.165}, pmid = {20345230}, issn = {1437-4331}, mesh = {Aged ; Asbestos/*toxicity ; Biomarkers, Tumor/blood ; Blood Glucose/analysis ; Carcinogens/*toxicity ; Creatinine/blood ; Demography ; *Environmental Exposure ; Female ; GPI-Linked Proteins ; Glomerular Filtration Rate ; Humans ; Male ; Membrane Glycoproteins/*blood ; Mesothelin ; Mesothelioma/blood/chemically induced/diagnosis ; Middle Aged ; Pleural Neoplasms/blood/chemically induced/diagnosis ; Risk Factors ; }, abstract = {BACKGROUND: Soluble mesothelin-related protein (SMRP) is increased in the sera of patients with malignant mesothelioma (MM), and has been suggested as a diagnostic tool for MM in an asbestos exposed population. However, factors affecting SMRP concentrations in normal subjects and those with other asbestos related disorders have not been investigated in any large population based study.

METHODS: Five hundred and thirty-eight subjects with a history of asbestos exposure were studied. Age, height, weight, body mass index (BMI), serum creatinine and glucose, estimated glomerular filtration rate (eGFR) and lung function were compared with SMRP concentrations.

RESULTS: The mean age [+/- standard deviation (SD)] of participants was 66.9 (+/-10.1) years, and mean (+/-SD) serum SMRP concentration was 0.91 (+/-0.67) nmol/L. SMRP values were inversely associated with weight (Pearson r=-0.1254, p=0.0036), BMI (Pearson r=-0.1594, p=0.0002), blood glucose (Pearson r=-0.1515, p=0.0004), single-breath carbon monoxide diffusing capacity (DLco) % predicted (Pearson r=-0.1847, p<0.0001), eGFR (Pearson r=-0.2835, p<0.0001) and single-breath carbon monoxide diffusing capacity per unit alveolar volume (DLco/VA)% predicted (Pearson r=-0.1872, p<0.0001) but were positively associated with age (Pearson r=0.2315, p<0.0001) and creatinine (Pearson r=0.3833, p<0.0001).

CONCLUSIONS: This study has shown that demographic variables, physiological factors and lung function are associated with serum SMRP concentrations. Confounding factors should be considered when interpreting serum SMRP.}, } @article {pmid20338867, year = {2010}, author = {Vudrag, M and Rihtar, TK and Vegnuti, M}, title = {Mesothelioma risk associated with asbestos production in Slovenia.}, journal = {Arhiv za higijenu rada i toksikologiju}, volume = {61}, number = {1}, pages = {45-52}, doi = {10.2478/10004-1254-61-2010-1939}, pmid = {20338867}, issn = {1848-6312}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Humans ; Incidence ; Mesothelioma/chemically induced/*epidemiology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/chemically induced/epidemiology ; Poisson Distribution ; Slovenia/epidemiology ; Young Adult ; }, abstract = {The aim of this study was to assess malignant mesothelioma morbidity due to exposure to asbestos in a population living in districts Nova Gorica and Tolmin (49,850 people) near the asbestos manufacturing village Anhovo (Slovenia) and to compare it with the entire Slovene population (1,949,750 people). Crude rates per 100,000 people were calculated from the total number of mesotheliomas, and risk assessment in the studied vs. total population was based on 23 years worth of data. Time series data on mesothelioma cases were also processed as a forecast of new cases by 2010.The crude incidence of mesothelioma per 100,000 individuals for all of Slovenia was 21.4, while for the Nova Gorica district including the village Anhovo it is 170.2 and for the Tolmin district 60.9. The probability of a mesothelioma case in the studied population was 8.5 times the probability of the same diagnosis in the whole of Slovenia. Over 23 years, 28% of all mesothelioma cases in Slovenia were diagnosed in the studied population, which makes only 2.5% of the total Slovene population.The outbreak of asbestosis and mesothelioma epidemics in the studied population is associated with manufacture of asbestos products in the local factory from 1922 to 1996.}, } @article {pmid20308261, year = {2010}, author = {Hannaford-Turner, K and Elder, D and Sim, MR and Abramson, MJ and Johnson, AR and Yates, DH}, title = {Surveillance of Australian workplace Based Respiratory Events (SABRE) in New South Wales.}, journal = {Occupational medicine (Oxford, England)}, volume = {60}, number = {5}, pages = {376-382}, doi = {10.1093/occmed/kqq011}, pmid = {20308261}, issn = {1471-8405}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Incidence ; Lung Diseases/*epidemiology ; Male ; Middle Aged ; New South Wales/epidemiology ; Occupational Diseases/*epidemiology ; Sex Distribution ; Young Adult ; }, abstract = {BACKGROUND: The Surveillance of Australian workplace Based Respiratory Events (SABRE) New South Wales (NSW) scheme is a voluntary notification scheme established to determine the incidence of occupational lung diseases in NSW Australia.

AIMS: Data presented in this paper summarize the last 7 years of reporting to SABRE (June 2001 to December 2008).

METHODS: Every 2 months, participating occupational physicians, respiratory physicians and general practitioners (accredited by the NSW WorkCover Authority) reported new cases of occupational lung disease seen in their practices. Data collected include gender, age, causal agent and the occupations and industries believed responsible. Estimated incidence was calculated for each disease.

RESULTS: Three thousand six hundred and fifty-four cases were notified to the scheme, consisting of 3856 diagnoses. Most of the cases were males (76%). Pleural plaques [1218 (28%)] were the most frequently reported condition, followed by mesothelioma [919 (24%)]. Silicosis [90 (2%)] and occupational asthma [OA; 89 (2%)] were the most frequently reported non-asbestos-related diseases. Estimated rates for mesothelioma, diffuse pleural thickening (DPT) and OA were 83, 83 and 5 cases per million employed males per year, respectively. Trades such as carpenters and electricians associated with the building industry, electricity supply and asbestos product manufacture were the most common occupations and industries reported.

CONCLUSIONS: Asbestos-related diseases are the most frequently reported conditions to SABRE NSW. The very low incidence of OA for NSW most likely reflects under-diagnosis as well as under-reporting. Occupational lung disease is still occurring in NSW despite current preventative strategies. The SABRE scheme currently provides the only available information in this area.}, } @article {pmid20307263, year = {2010}, author = {Donaldson, K and Murphy, FA and Duffin, R and Poland, CA}, title = {Asbestos, carbon nanotubes and the pleural mesothelium: a review of the hypothesis regarding the role of long fibre retention in the parietal pleura, inflammation and mesothelioma.}, journal = {Particle and fibre toxicology}, volume = {7}, number = {}, pages = {5}, pmid = {20307263}, issn = {1743-8977}, support = {//Department of Health/United Kingdom ; }, mesh = {Air Pollutants/*pharmacokinetics/toxicity ; Animals ; Asbestos/*pharmacokinetics/toxicity ; Disease Models, Animal ; Epithelium/drug effects/*metabolism/ultrastructure ; Humans ; Mesothelioma/chemically induced/*metabolism/pathology ; Metabolic Clearance Rate ; Mice ; Mineral Fibers ; *Nanotubes, Carbon ; Particle Size ; Pleura/drug effects/*metabolism/ultrastructure ; }, abstract = {The unique hazard posed to the pleural mesothelium by asbestos has engendered concern in potential for a similar risk from high aspect ratio nanoparticles (HARN) such as carbon nanotubes. In the course of studying the potential impact of HARN on the pleura we have utilised the existing hypothesis regarding the role of the parietal pleura in the response to long fibres. This review seeks to synthesise our new data with multi-walled carbon nanotubes (CNT) with that hypothesis for the behaviour of long fibres in the lung and their retention in the parietal pleura leading to the initiation of inflammation and pleural pathology such as mesothelioma. We describe evidence that a fraction of all deposited particles reach the pleura and that a mechanism of particle clearance from the pleura exits, through stomata in the parietal pleura. We suggest that these stomata are the site of retention of long fibres which cannot negotiate them leading to inflammation and pleural pathology including mesothelioma. We cite thoracoscopic data to support the contention, as would be anticipated from the preceding, that the parietal pleura is the site of origin of pleural mesothelioma. This mechanism, if it finds support, has important implications for future research into the mesothelioma hazard from HARN and also for our current view of the origins of asbestos-initiated pleural mesothelioma and the common use of lung parenchymal asbestos fibre burden as a correlate of this tumour, which actually arises in the parietal pleura.}, } @article {pmid20298508, year = {2010}, author = {Kao, SC and Reid, G and Lee, K and Vardy, J and Clarke, S and van Zandwijk, N}, title = {Malignant mesothelioma.}, journal = {Internal medicine journal}, volume = {40}, number = {11}, pages = {742-750}, doi = {10.1111/j.1445-5994.2010.02223.x}, pmid = {20298508}, issn = {1445-5994}, mesh = {Animals ; Asbestos/*toxicity ; Australia/epidemiology ; Environmental Exposure/*adverse effects ; Humans ; Mesothelioma/*epidemiology/*etiology/therapy ; }, abstract = {Malignant mesothelioma (MM) is an aggressive tumour that commonly affects the mesothelial surfaces of the pleural and peritoneal cavities, and occasionally, the tunica vaginalis and the pericardium. Formerly a rare tumour, MM is increasing in incidence in Australia due to the heavy nationwide use of asbestos from 1940 until the 1980s. The incidence is expected to peak in Australia in the next decade, mirroring the long latency period between asbestos exposure and development of MM. Diagnosis of MM can be difficult. Definitive pathological diagnosis is required and it often requires an experienced pathologist to differentiate MM from other benign or malignant processes. Treatment of MM requires a multidisciplinary approach, regardless of palliative or curative intent. Treatment options, such as surgery, chemotherapy, radiotherapy and active symptom control or a combination of these, may be used. Further research is needed to advance the therapeutic options for MM, and strategies to realize personalisation of therapy through discovery of predictive markers. In the Australian society where asbestos contamination of the built environment is very high, education and stringent public health measures are required to prevent a second wave of increased MM incidence.}, } @article {pmid20230253, year = {2010}, author = {Price, B}, title = {Industrial-grade talc exposure and the risk of mesothelioma.}, journal = {Critical reviews in toxicology}, volume = {40}, number = {6}, pages = {513-530}, doi = {10.3109/10408441003646781}, pmid = {20230253}, issn = {1547-6898}, mesh = {Air Pollutants, Occupational/classification/*toxicity ; Animals ; Asbestos/toxicity ; Carcinogenicity Tests ; Carcinogens/classification/*toxicity ; Carcinogens, Environmental/classification/*toxicity ; Government Agencies/standards ; Government Regulation ; Humans ; Mesothelioma/*epidemiology/etiology ; Mineral Fibers ; Risk Assessment ; Talc/classification/*toxicity ; United States/epidemiology ; }, abstract = {Industrial-grade talc deposits are complex mixtures of mineral particles and may vary substantially in composition across small geographical areas. Typical industrial-grade talc includes amphibole cleavage fragments, platy talc, serpentine minerals, talc in fibrous form, and a minor presence of transitional fibers. Industrial-grade talc was erroneously determined to be an asbestos-containing material due to an unintended consequence of Occupational Health and Safety Administration's (OSHA's) method for measuring airborne asbestos mandated in 1972. This error was repeated, most notably, by the National Institute for Occupational Safety and Health (NIOSH) in, 1980 for talc mined in northern New York State (NYS) by RT Vanderbilt Company (RTV). Subsequent exposure studies of northern NYS talc conducted through the, 1980s and one study published after, 2000 relied on the conclusion that talc was an asbestos-containing material to infer a causal relationship between talc and mesothelioma. The present review included (1) publications concerning talc's cancer-causing potential issued by organizations concerned with occupational and public health; (2) talc exposure studies and animal and cellular studies of RTV talc; (3) mesothelioma rates in northern NYS; and (4) mesothelioma mortality among RTV mining employees. The review indicated that failure to correctly identify the mineral characteristics of talc resulted in misleading reports concerning the carcinogenic potential of talc. However, the collective data from animal and cellular studies, mesothelioma rates in northern NYS, exposure studies, and a mortality analysis of RTV mining employees do not support a causal relationship between RTV talc and mesothelioma. This conclusion is applicable to all mineral components in RTV talc and to other industrial-grade talcs and mineral aggregates with the same components.}, } @article {pmid20213099, year = {2010}, author = {Fujimoto, N and Aoe, K and Gemba, K and Kato, K and Yamazaki, K and Kishimoto, T}, title = {Clinical investigation of malignant mesothelioma in Japan.}, journal = {Journal of cancer research and clinical oncology}, volume = {136}, number = {11}, pages = {1755-1759}, pmid = {20213099}, issn = {1432-1335}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Japan ; Male ; Mesothelioma/mortality/*pathology ; Middle Aged ; Peritoneal Neoplasms/mortality/pathology ; Pleural Neoplasms/mortality/pathology ; Survival Analysis ; Time Factors ; }, abstract = {PURPOSE: The asbestos-related problems caused much social concern; however, no large-scale study was conducted about clinical features of MM in Japan. Patients with MM who have a history of occupational asbestos exposure (AE) are provided worker's compensation in Japan. However, only about 10% of MM cases were actually claimed and compensated. So there is still controversy over the association between MM and AE. The aim of this study is to investigate the clinical features of MM. We also aimed to clarify the association between MM and occupational AE in Japan.

METHODS: We examined the clinical features of MM cases. Clinical information was obtained including gender, age, site of origin, pathological subtype, radiological findings, and treatment outcome. To investigate the association between MM and AE, investigators interviewed all patients regarding work and residential history.

RESULTS: Between January 2005 and December 2007, 105 cases (median age: 63 years, range 35-80, male/female: 88/17) were diagnosed with MM in the Rosai Hospital group and related facilities. Among them, 94(89.5%) cases originated in the pleura, 7(6.7%) in the peritoneum, 2(1.9%) in the pericardium, and 1(0.9%) in the tunica vaginalis testis. There were 69(65.7%) epithelioid, 19(18.1%) biphasic, 16(15.2%) sarcomatoid, and 1 unclassified pathological subtypes of MM. A favorable survival rate was indicated in the patient group of MPM that underwent surgery compared to others, though it was not statistically significant (P = 0.1743). The occupational AE was indicated in 89 cases (84.8%). Three patients had no history of occupational AE, but lived with someone who was in an occupation that handled asbestos. There were two patients in which AE was indicated in their life environment. Altogether, AE was indicated in 93(88.6%) patients.

CONCLUSIONS: This study stresses the urgent need for physicians to acknowledge the association between MM and AE, and to inquire thoroughly regarding AE to the patients with MM.}, } @article {pmid20202918, year = {2010}, author = {Kashanskiy, SV and André, N}, title = {[Paediatric mésothelioma: is there the such a disease?].}, journal = {Bulletin du cancer}, volume = {97}, number = {5}, pages = {571-576}, doi = {10.1684/bdc.2010.1064}, pmid = {20202918}, issn = {1769-6917}, mesh = {Adolescent ; Age Factors ; Asbestos/toxicity ; Carcinogens, Environmental/toxicity ; Child ; Child, Preschool ; Environmental Exposure ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Mesothelioma/*epidemiology/pathology ; Rare Diseases/*epidemiology/pathology ; Sex Distribution ; Young Adult ; }, abstract = {Paediatric mesothelioma is a very rare entity. We report here epidemiologic data from 489 cases reported in international medical literature. A better knowledge about this entity is mandatory to improve its management.}, } @article {pmid22993544, year = {2010}, author = {Fujimoto, N and Gemba, K and Asano, M and Wada, S and Ono, K and Ozaki, S and Kishimoto, T}, title = {Soluble mesothelin-related protein in pleural effusion from patients with malignant pleural mesothelioma.}, journal = {Experimental and therapeutic medicine}, volume = {1}, number = {2}, pages = {313-317}, pmid = {22993544}, issn = {1792-0981}, abstract = {Malignant pleural mesothelioma (MPM) is a highly aggressive neoplasm primarily arising from surface serosal cells of the pleura and is strongly associated with asbestos exposure. Patients with MPM often develop pleural fluid as initial presentation. However, cytological diagnosis using pleural fluid is usually difficult and has limited utility. A useful molecular marker for differential diagnosis particularly with lung cancer (LC) is urgently needed. The aim of the present study was to investigate the diagnostic value of soluble mesothelin-related protein (SMRP) in pleural fluid. Pleural fluids were collected from 23 patients with MPM, 38 with LC, 26 with benign asbestos pleurisy (BAP), 5 with tuberculosis pleurisy (TP) and 4 with chronic heart failure (CHF), and the SMRP concentration was determined. All data were analyzed by using non-parametric two-sided statistical tests. The median concentration of SMRP in MPM, LC, BAP, TP and CHF were 11.5 (range 0.90-82.80), 5.20 (0.05-36.40), 6.65 (1.45-11.25), 3.20 (1.65-6.50) and 2.03 (1.35-2.80) nmol/l, respectively. The SMRP concentration was significantly higher in MPM than in the other diseases (P=0.001). The area under the ROC curve (AUC) values of the MPM diagnosis was 0.75 for the differential diagnosis from the other groups. Based on the cut-off value of 8 nmol/l, the sensitivity and specificity for diagnosis of MPM were 70.0 and 68.4%, respectively. These results indicate that the SMRP concentration in pleural fluid is a useful marker for the diagnosis of MPM.}, } @article {pmid20185425, year = {2010}, author = {Tabata, C and Hirayama, N and Tabata, R and Yasumitsu, A and Yamada, S and Murakami, A and Iida, S and Tamura, K and Fukuoka, K and Kuribayashi, K and Terada, T and Nakano, T}, title = {A novel clinical role for angiopoietin-1 in malignant pleural mesothelioma.}, journal = {The European respiratory journal}, volume = {36}, number = {5}, pages = {1099-1105}, doi = {10.1183/09031936.00154009}, pmid = {20185425}, issn = {1399-3003}, mesh = {Angiopoietin-1/*blood/*genetics ; Angiopoietin-2/genetics/metabolism ; Animals ; Asbestosis/metabolism/pathology ; Biomarkers/blood ; Cell Division/physiology ; Cell Line, Tumor ; Cell Movement/physiology ; Female ; Fibroblasts/cytology ; Humans ; Kaplan-Meier Estimate ; Mice ; Mice, SCID ; Neoplasms, Mesothelial/*metabolism/mortality/pathology ; Pleural Neoplasms/*metabolism/mortality/pathology ; Prognosis ; RNA, Messenger/metabolism ; Receptor, TIE-2/genetics/metabolism ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive malignant tumour associated with asbestos exposure that has only a limited response to conventional therapy; therefore, diagnosing MPM early is very important. We have previously reported that angiopoietin (Ang)-1 was correlated with bleomycin-induced pulmonary fibrosis. Here, we investigated the association of Ang-1 with the development of MPM cells, which originate from mesenchymal cells similar to lung fibroblasts, and demonstrated that Ang-1 stimulated the growth and migration of MPM cells in vitro. We also demonstrated that patients with MPM had significantly higher serum levels of Ang-1 in comparison to a population who had been exposed to asbestos but had not developed MPM. The patients with advanced-stage MPM showed higher levels of Ang-1 than the early-stage MPM patients and the Kaplan-Meier method revealed a significant correlation between serum Ang-1 levels and survival. We propose the possibility that Ang-1 plays an important role in MPM tumour growth and our data suggest that the serum concentration of Ang-1 could be useful as prognostic factor.}, } @article {pmid20171954, year = {2010}, author = {Takemura, Y and Satoh, M and Satoh, K and Hamada, H and Sekido, Y and Kubota, S}, title = {High dose of ascorbic acid induces cell death in mesothelioma cells.}, journal = {Biochemical and biophysical research communications}, volume = {394}, number = {2}, pages = {249-253}, doi = {10.1016/j.bbrc.2010.02.012}, pmid = {20171954}, issn = {1090-2104}, mesh = {Animals ; *Apoptosis ; Ascorbic Acid/*administration & dosage ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Humans ; Membrane Potential, Mitochondrial/drug effects ; Mesothelioma/*drug therapy ; Mice ; Mice, SCID ; Reactive Oxygen Species/metabolism ; Xenograft Model Antitumor Assays ; }, abstract = {Malignant mesothelioma is an asbestos-related fatal disease with no effective cure. Recently, high dose of ascorbate in cancer treatment has been reexamined. We studied whether high dose of ascorbic acid induced cell death of four human mesothelioma cell lines. High dose of ascorbic acid induced cell death of all mesothelioma cell lines in a dose-dependent manner. We further clarified the cell killing mechanism that ascorbic acid induced reactive oxygen species and impaired mitochondrial membrane potential. In vivo experiment, intravenous administration of ascorbic acid significantly decreased the growth rate of mesothelioma tumor inoculated in mice. These data suggest that ascorbic acid may have benefits for patients with mesothelioma.}, } @article {pmid20170978, year = {2010}, author = {Ugolini, D and Neri, M and Casilli, C and Ceppi, M and Canessa, PA and Ivaldi, GP and Paganuzzi, M and Bonassi, S}, title = {A bibliometric analysis of scientific production in mesothelioma research.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {70}, number = {2}, pages = {129-135}, doi = {10.1016/j.lungcan.2010.01.013}, pmid = {20170978}, issn = {1872-8332}, mesh = {Europe ; Gross Domestic Product/statistics & numerical data ; Health Policy ; Humans ; *Journal Impact Factor ; Lung Neoplasms/economics/*epidemiology/pathology ; Mesothelioma/economics/*epidemiology/pathology ; *Population ; *Research/statistics & numerical data ; Serial Publications/statistics & numerical data/trends ; United States ; }, abstract = {This study aims at comparing scientific production in malignant mesothelioma (MM) among countries and evaluating publication trends and impact factor (IF). The PubMed database was searched with a strategy combining keywords listed in the Medical Subject Headings and free-text search. Publications numbers and IF were evaluated both as absolute values and after standardization by population and gross domestic product (GDP). 5240 citations were retrieved from the biennium 1951-1952 (n = 22) to 2005-2006 (n = 535). The 177% increase of MM publications from 1987 to 2006 exceeded by large the corresponding value of total cancer literature (123.5%). In these two decades, 2559 articles with IF were published: 46.4% came from the European Union (EU) (the UK, Italy and France ranking at the top), and 36.2% from the US. The highest mean IF was reported for the US (3.346), followed by Australia (3.318), and EU (2.415, with the UK, Belgium and the Netherlands first). Finland, Sweden and Australia had the best ratio between IF (sum) and resident population or GDP. The number of publications correlated with GDP (p = 0.001) and national MM mortality rates (p = 0.002). An association was found between a country commitment to MM research and the burden of disease (p = 0.04). Asbestos, survival, prognosis, occupational exposure, differential diagnosis, and immunohistochemistry were the most commonly used keywords. This report represents the first effort to explore the geographical and temporal distribution of MM research and its determinants. This is an essential step in understanding science priorities and developing disease control policies.}, } @article {pmid20160038, year = {2010}, author = {Pass, HI and Goparaju, C and Ivanov, S and Donington, J and Carbone, M and Hoshen, M and Cohen, D and Chajut, A and Rosenwald, S and Dan, H and Benjamin, S and Aharonov, R}, title = {hsa-miR-29c* is linked to the prognosis of malignant pleural mesothelioma.}, journal = {Cancer research}, volume = {70}, number = {5}, pages = {1916-1924}, pmid = {20160038}, issn = {1538-7445}, support = {U01 CA111295/CA/NCI NIH HHS/United States ; U01 CA111295-03/CA/NCI NIH HHS/United States ; U01CA1111295/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/poisoning ; Cell Line, Tumor ; Female ; Humans ; Male ; Mesothelioma/etiology/*genetics ; MicroRNAs/*analysis/biosynthesis/genetics ; Middle Aged ; Pleural Neoplasms/etiology/*genetics ; Prognosis ; Reproducibility of Results ; Reverse Transcriptase Polymerase Chain Reaction/methods ; Transfection ; }, abstract = {The inability to forecast outcomes for malignant mesothelioma prevents clinicians from providing aggressive multimodality therapy to the most appropriate individuals who may benefit from such an approach. We investigated whether specific microRNAs (miR) could segregate a largely surgically treated group of mesotheliomas into good or bad prognosis categories. A training set of 44 and a test set of 98 mesothelioma tumors were analyzed by a custom miR platform, along with 9 mesothelioma cell lines and 3 normal mesothelial lines. Functional implications as well as downstream targets of potential prognostic miRs were investigated. In both the training and test sets, hsa-miR-29c* was an independent prognostic factor for time to progression as well as survival after surgical cytoreduction. The miR was expressed at higher levels in epithelial mesothelioma, and the level of this miR could segregate patients with this histology into groups with differing prognosis. Increased expression of hsa-miR-29c* predicted a more favorable prognosis, and overexpression of the miR in mesothelioma cell lines resulted in significantly decreased proliferation, migration, invasion, and colony formation. Moreover, major epigenetic regulation of mesothelioma is mediated by hsa-miR-29c* and was shown through downregulation of DNA methyltransferases as well as upregulation of demethylating genes. A single miR has the potential to be a prognostic biomarker in mesothelioma, and validation of these findings as well as investigation of its downstream targets may give insight for potential therapies in the future.}, } @article {pmid20155583, year = {2010}, author = {Hillegass, JM and Shukla, A and MacPherson, MB and Bond, JP and Steele, C and Mossman, BT}, title = {Utilization of gene profiling and proteomics to determine mineral pathogenicity in a human mesothelial cell line (LP9/TERT-1).}, journal = {Journal of toxicology and environmental health. Part A}, volume = {73}, number = {5}, pages = {423-436}, pmid = {20155583}, issn = {1528-7394}, support = {P30 CA022435/CA/NCI NIH HHS/United States ; T32 ES007122/ES/NIEHS NIH HHS/United States ; T32 ES007122-17/ES/NIEHS NIH HHS/United States ; }, mesh = {Asbestos, Crocidolite/toxicity ; Cell Line ; Epithelium/*drug effects/metabolism ; Fibroblast Growth Factor 2/genetics/metabolism ; Gene Expression/drug effects ; Gene Expression Profiling/*methods ; Granulocyte Colony-Stimulating Factor/genetics/metabolism ; Humans ; Interleukin-13/genetics/metabolism ; Particulate Matter/*toxicity ; Proteomics ; Talc/toxicity ; Telomerase/genetics ; Titanium/toxicity ; Toxicity Tests/*methods ; Tumor Necrosis Factor-alpha/genetics/metabolism ; Vascular Endothelial Growth Factor A/genetics/metabolism ; }, abstract = {Identifying and understanding the early molecular events that underscore mineral pathogenicity using in vitro screening tests is imperative, especially given the large number of synthetic and natural fibers and particles being introduced into the environment. The purpose of the work described here was to examine the ability of gene profiling (Affymetrix microarrays) to predict the pathogenicity of various materials in a human mesothelial cell line (LP9/TERT-1) exposed to equal surface area concentrations (15 x 10(6) or 75 x 10(6) microm(2)/cm(2)) of crocidolite asbestos, nonfibrous talc, fine titanium dioxide (TiO(2)), or glass beads for 8 or 24 h. Since crocidolite asbestos caused the greatest number of alterations in gene expression, multiplex analysis (Bio-Plex) of proteins released from LP9/TERT-1 cells exposed to crocidolite asbestos was also assessed to reveal if this approach might also be explored in future assays comparing various mineral types. To verify that LP9/TERT-1 cells were more sensitive than other cell types to asbestos, human ovarian epithelial cells (IOSE) were also utilized in microarray studies. Upon assessing changes in gene expression via microarrays, principal component analysis (PCA) of these data was used to identify patterns of differential gene expression. PCA of microarray data confirmed that LP9/TERT-1 cells were more responsive than IOSE cells to crocidolite asbestos or nonfibrous talc, and that crocidolite asbestos elicited greater responses in both cell types when compared to nonfibrous talc, TiO(2), or glass beads. Bio-Plex analysis demonstrated that asbestos caused an increase in interleukin-13 (IL-13), basic fibroblast growth factor (bFGF), granulocyte colony-stimulating factor (G-CSF), and vascular endothelial growth factor (VEGF). These responses were generally dose-dependent (bFGF and G-CSF only) and tumor necrosis factor (TNF)-alpha independent (except for G-CSF). Thus, microarray and Bio-Plex analyses are valuable in determining early molecular responses to fibers/particles and may directly contribute to understanding the etiology of diseases caused by them. The number and magnitude of changes in gene expression or "profiles" of secreted proteins may serve as valuable metrics for determining the potential pathogenicity of various mineral types. Hence, alterations in gene expression and cytokine/chemokine changes induced by crocidolite asbestos in LP9/TERT-1 cells may be indicative of its increased potential to cause mesothelioma in comparison to the other nonfibrous materials examined.}, } @article {pmid20155580, year = {2010}, author = {Pacurari, M and Castranova, V and Vallyathan, V}, title = {Single- and multi-wall carbon nanotubes versus asbestos: are the carbon nanotubes a new health risk to humans?.}, journal = {Journal of toxicology and environmental health. Part A}, volume = {73}, number = {5}, pages = {378-395}, doi = {10.1080/15287390903486527}, pmid = {20155580}, issn = {1528-7394}, mesh = {Asbestos/chemistry/*toxicity ; Carcinogens/chemistry/*toxicity ; Carcinoma, Bronchogenic/chemically induced ; DNA Damage ; Epithelium/metabolism ; Humans ; Mesothelioma/chemically induced ; Mitogen-Activated Protein Kinases/metabolism ; NF-kappa B/metabolism ; Nanotubes, Carbon/chemistry/*toxicity ; Particle Size ; Risk Assessment ; Signal Transduction/drug effects ; Transcription Factor AP-1/metabolism ; }, abstract = {Carbon nanotubes (CNT), since their discovery, have become one of the most promising nanomaterials in many industrial and biomedical applications. Due to their unique physicochemical properties, interest is growing in the manufacture of CNT-based products and their subsequent marketing. Since their discovery, the prospect of possible undesirable human health effects has been a focus of many scientific studies. Although CNT possess unique physical properties that include (1) nanoscale diameter, (2) a wide length distribution ranging from tens of nanometers to several micrometers, and (3) high aspect ratio, the fibrous-like shape and durability suggest that their toxic properties may be analogous to those observed with other fibrous particles, such as asbestos. The present study provides a summary of published findings on CNT bioactivity, such as the potential of CNT, especially of multi-wall carbon nanotubes (MWCNT), to activate signaling pathways modulating transcription factor activity, induce apoptosis, induce DNA damage, and initiate biological responses. Assessment of risks to human health and adoption of appropriate exposure controls is critical for the safe and successful introduction of CNT -based products for future applications.}, } @article {pmid20155346, year = {2010}, author = {Maeda, R and Isowa, N and Onuma, H and Miura, H and Tokuyasu, H and Kawasaki, Y}, title = {Minute localized malignant pleural mesothelioma coexisting with multiple adenocarcinomas.}, journal = {General thoracic and cardiovascular surgery}, volume = {58}, number = {2}, pages = {91-94}, pmid = {20155346}, issn = {1863-6713}, mesh = {Adenocarcinoma/diagnostic imaging/*pathology/surgery ; Biopsy ; Female ; Humans ; Immunohistochemistry ; Lymph Node Excision ; Middle Aged ; *Neoplasms, Multiple Primary ; Pleural Neoplasms/diagnostic imaging/*pathology/surgery ; Predictive Value of Tests ; Solitary Fibrous Tumor, Pleural/diagnostic imaging/*pathology/surgery ; Thoracic Surgery, Video-Assisted ; Tomography, X-Ray Computed ; Treatment Outcome ; }, abstract = {We report an extremely rare case of minute localized malignant pleural mesothelioma (LMPM) coexisting with multiple lung adenocarcinomas in a 64-year-old woman without a history of smoking or asbestos exposure. A computed tomography scan of the chest displayed total five ground-glass opacities in the lung. Transbronchial lung biopsy from a ground-glass opacity in the posterior segment revealed a bronchioloalveolar carcinoma. With a diagnosis of primary lung cancer, right upper lobectomy and wedge resection of the right lower lobe with systematic lymph node dissection was performed using video-assisted thoracoscopic surgery. Incidentally, a minute gray-white nodule measuring 6 mm was detected on the visceral pleural surface of the right upper lobe. The postoperative histological diagnosis was minute LMPM coexisting with multiple adenocarcinomas.}, } @article {pmid20153416, year = {2010}, author = {Sudo, H and Tsuji, AB and Sugyo, A and Kohda, M and Sogawa, C and Yoshida, C and Harada, YN and Hino, O and Saga, T}, title = {Knockdown of COPA, identified by loss-of-function screen, induces apoptosis and suppresses tumor growth in mesothelioma mouse model.}, journal = {Genomics}, volume = {95}, number = {4}, pages = {210-216}, doi = {10.1016/j.ygeno.2010.02.002}, pmid = {20153416}, issn = {1089-8646}, mesh = {Animals ; Apoptosis/*genetics ; Cell Line, Tumor ; Cell Proliferation ; Coatomer Protein/*genetics ; Gene Knockdown Techniques ; Humans ; Mesothelioma/*genetics ; Mice ; Pleural Neoplasms/*genetics ; RNA, Small Interfering/genetics ; }, abstract = {Malignant mesothelioma is a highly aggressive tumor arising from serosal surfaces of the pleura and is triggered by past exposure to asbestos. Currently, there is no widely accepted treatment for mesothelioma. Development of effective drug treatments for human cancers requires identification of therapeutic molecular targets. We therefore conducted a large-scale functional screening of mesothelioma cells using a genome-wide small interfering RNA library. We determined that knockdown of 39 genes suppressed mesothelioma cell proliferation. At least seven of the 39 genes-COPA, COPB2, EIF3D, POLR2A, PSMA6, RBM8A, and RPL18A-would be involved in anti-apoptotic function. In particular, the COPA protein was highly expressed in some mesothelioma cell lines but not in a pleural mesothelial cell line. COPA knockdown induced apoptosis and suppressed tumor growth in a mesothelioma mouse model. Therefore, COPA may have the potential of a therapeutic target and a new diagnostic marker of mesothelioma.}, } @article {pmid20130785, year = {2010}, author = {Weber, DG and Johnen, G and Taeger, D and Weber, A and Gross, IM and Pesch, B and Kraus, T and Brüning, T and Gube, M}, title = {Assessment of Confounding Factors Affecting the Tumor Markers SMRP, CA125, and CYFRA21-1 in Serum.}, journal = {Biomarker insights}, volume = {5}, number = {}, pages = {1-8}, pmid = {20130785}, issn = {1177-2719}, abstract = {The purpose of this analysis was to evaluate if serum levels of potential tumor markers for the diagnosis of malignant mesothelioma and lung cancer are affected by confounding factors in a surveillance cohort of workers formerly exposed to asbestos. SMRP, CA125, and CYFRA21-1 concentrations were determined in about 1,700 serum samples from 627 workers formerly exposed to asbestos. The impact of factors that could modify the concentrations of the tumor markers was examined with linear mixed models. SMRP values increased with age 1.02-fold (95% CI 1.01-1.03) and serum creatinine concentration 1.32-fold (95% CI 1.20-1.45). Levels differed by study centers and were higher after 40 years of asbestos exposure. CA125 levels increased with longer storage of the samples. CYFRA21-1 values correlated with age 1.02-fold (95% CI 1.01-1.02), serum creatinine 1.21-fold (95% CI 1.14-1.30) and varied by study centers due to differences in sample handling. Tumor marker concentrations are influenced by subject-related factors, sample handling, and storage. These factors need to be taken into account in screening routine.}, } @article {pmid20123454, year = {2010}, author = {Colonna, A and Gualco, G and Bacchi, CE and Leite, MA and Rocco, M and DeMaglio, G and Pizzolitto, S and Falconieri, G}, title = {Plasma cell myeloma presenting with diffuse pleural involvement: a hitherto unreported pattern of a new mesothelioma mimicker.}, journal = {Annals of diagnostic pathology}, volume = {14}, number = {1}, pages = {30-35}, doi = {10.1016/j.anndiagpath.2009.10.005}, pmid = {20123454}, issn = {1532-8198}, mesh = {Aged, 80 and over ; Biopsy ; Diagnosis, Differential ; Fatal Outcome ; Female ; Humans ; Immunoglobulin kappa-Chains/metabolism ; Immunohistochemistry ; Male ; Mesothelioma/*pathology ; Middle Aged ; Multiple Myeloma/*pathology ; Pleura/metabolism/*pathology ; Pleural Neoplasms/*pathology ; }, abstract = {We described 2 cases of plasmacytoma presenting with a preponderant involvement of the pleural membranes simulating clinically, radiologically, and on gross pathologic inspection a primary mesothelioma. The patients were an 80-year-old man and a 45-year-old woman. In both cases, the clinical presentation was that of a serosal tumor, including effusions and pleural thickening. In the former, the serosal infiltration raised the suspicion of mesothelioma reinforced by history of occupational exposure to asbestos. Patient general condition deteriorated rapidly. Postmortem examination revealed unilateral encasing of the lung within a thick, irregular neoplastic rind. In addition, tumoral involvement was seen in the homolateral third rib and the clavicle. Histologic examination of pleural masses demonstrated diffuse infiltration by highly atypical, pleomorphic plasma cells with kappa chain restriction. In the second case, clinical presentation was also suspicious of mesothelioma. Nonetheless, a pleural biopsy specimen showed irregular sheets of plasma cells showing kappa light chain restriction. A bone marrow aspirate was also positive for abnormal plasma cell infiltrates. Despite chemotherapy, the patient died 4 months after presentation. Although rarely, it seems that plasmacytoma may present with an exclusive or preponderant pleural involvement; and it may therefore be added to the list of pseudomesotheliomatous tumors.}, } @article {pmid20117025, year = {2011}, author = {Patel, J and Sheppard, MN}, title = {Primary malignant mesothelioma of the pericardium.}, journal = {Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology}, volume = {20}, number = {2}, pages = {107-109}, doi = {10.1016/j.carpath.2010.01.005}, pmid = {20117025}, issn = {1879-1336}, mesh = {Aged ; Anticoagulants/therapeutic use ; Atrial Fibrillation/complications/drug therapy ; Carotid Artery Diseases/complications/surgery ; Endarterectomy, Carotid ; Fatal Outcome ; Glaucoma/complications ; Heart Neoplasms/complications/*pathology ; Humans ; Male ; Mesothelioma/complications/*pathology ; Pericardial Effusion/etiology ; Pericardium/*pathology ; Warfarin/therapeutic use ; }, abstract = {Primary malignant pericardial mesothelioma is an extremely rare tumor. One of the largest autopsy series gave an incidence of primary pericardial tumors of 0.0022%, of which mesothelioma is the most common type. A male predominance of the disease has been described, and the majority of cases occur in the fourth to seventh decades of life. Unlike peritoneal and pleural mesothelioma, there has been no definite correlation between asbestos exposure and pericardial disease. Malignant pericardial mesothelioma carries a poor prognosis with few successful treatment strategies and little benefit from radiation and chemotherapy. We report a case of a 66-year-old man who presented with shortness of breath, right shoulder pain, and peripheral edema of the lower limbs. A large pericardial effusion was seen on echocardiography, which was drained but the patient died the following day. A malignant tumor was found on autopsy and a final diagnosis of primary malignant pericardial mesothelioma was made following histopathological examination.}, } @article {pmid20116740, year = {2009}, author = {Rodríguez-Panadero, F and Pérez, MA and Moya, MA and Cruz, MI}, title = {[Management of pleural disease].}, journal = {Archivos de bronconeumologia}, volume = {45 Suppl 3}, number = {}, pages = {22-27}, doi = {10.1016/S0300-2896(09)72854-6}, pmid = {20116740}, issn = {1579-2129}, mesh = {Asbestos/adverse effects ; Biomarkers/blood ; Decision Trees ; Humans ; Mesothelioma/blood/etiology ; Pleural Diseases/*diagnosis/etiology/*therapy ; Pleural Neoplasms/blood/etiology ; }, abstract = {In view of the presentations in the First National Forum of Trainee Pneumologists, the present article focuses on infectious pleural effusions and on the study of possible markers of malignant disease in asbestos-exposed individuals. The yield of the distinct techniques for the diagnosis of tuberculous pleural effusion is assessed, with emphasis on analysis of sputum and pleural samples (fluid and tissue) for Mycobacteriumtuberculosis. The utility of adenosine deaminase (ADA) (in the absence of empyema, ADA > 70 U/l is diagnostic of tuberculous pleurisy, while values of less than 40 U/l exclude this diagnosis) and interferon gamma in pleural fluid (cut off: 3.7 Ul/ml) is also discussed. The management of complicated parapneumonic pleural effusions is stratified in four categories, depending on the anatomical and morphological (size and eventual presence of loculations), bacteriological (positivity or negativity of pleural fluid culture) and biochemical (pH/glucose) characteristics of the effusion. Finally, recently developed markers for the evaluation and follow-up of asbestos-exposed individuals are described, with special emphasis on serum determination of mesothelin levels, which seem highly promising as a marker of the development of mesothelioma in these cases. A multicenter study currently being performed in Spain found that soluble mesothelin-related protein (SMRP) levels higher than 0.55 nmol/L showed a sensitivity and specificity of 72% for the diagnosis of epithelial malignant mesothelioma.}, } @article {pmid20104177, year = {2010}, author = {Antonescu-Turcu, AL and Schapira, RM}, title = {Parenchymal and airway diseases caused by asbestos.}, journal = {Current opinion in pulmonary medicine}, volume = {16}, number = {2}, pages = {155-161}, doi = {10.1097/MCP.0b013e328335de61}, pmid = {20104177}, issn = {1531-6971}, mesh = {Asbestos/*adverse effects ; Asbestosis/diagnostic imaging/*etiology ; Humans ; Lung Diseases/*chemically induced/diagnostic imaging ; Lung Diseases, Obstructive/chemically induced/diagnostic imaging ; Lung Neoplasms/chemically induced/diagnostic imaging ; Mesothelioma/chemically induced/diagnostic imaging ; Tomography, X-Ray Computed ; }, abstract = {PURPOSE OF REVIEW: The extensive industrial use of asbestos for many decades has been linked to development of benign and malignant pleuropulmonary disease. This review summarizes newer evidence and ongoing controversies that exist in the literature regarding asbestos-related parenchymal and airway diseases.

RECENT FINDINGS: Asbestosis represents a significant respiratory problem despite the improvement in the workplace hygiene and a decrease in use of asbestos. The management of asbestosis remains challenging as currently there is no specific treatment. The role of asbestos exposure alone as a cause of chronic airway obstruction remains uncertain. The relationship between lung cancer and asbestos exposure alone and in combination with smoking has also been investigated. The benefit of screening for asbestos-related pleuropulmonary disease remains uncertain as does the use of computed tomography scanning for the purpose of screening.

SUMMARY: Future studies will help clarify the clinical issues and shape screening strategies for asbestos-exposed individuals.}, } @article {pmid20102076, year = {2009}, author = {Mise, K and Jurcev-Savicević, A and Bradarić, A and Perić, I and Barisić, I and Puntarić, D and Mise, J and Ilić, N}, title = {Increasing of malignant pleural mesothelioma: burning issue in Split-Dalmatian County, Croatia.}, journal = {Collegium antropologicum}, volume = {33}, number = {4}, pages = {1245-1250}, pmid = {20102076}, issn = {0350-6134}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Croatia/epidemiology ; Female ; Humans ; Incidence ; Male ; Mesothelioma/*epidemiology/prevention & control ; Middle Aged ; Occupational Exposure/*prevention & control/statistics & numerical data ; Occupations ; Pleural Neoplasms/*epidemiology/prevention & control ; Retrospective Studies ; Risk Factors ; }, abstract = {Asbestos-related diseases are one of the burning public health issues worldwide. The incidence and the epidemiological patterns of malignant pleural mesothelioma in Split-Dalmatian County, where a large part of Croatian industry related to asbestos processing and use have been situated were assessed in this study. The history of asbestos-related issues and development of current legislation in Croatia was also discussed briefly. Data on the incidence were collected retrospectively from the medical records of patients with malignant pleural mesothelioma treated at Department of Pulmonary Diseases University Hospital Split during the 2000-2007 period. A total of 137 new cases was recorded with the mean incidence of 3.55/100,000 and the trend was increasing over years compared with 1992-1995 period in the same county when the mean incidence was 1.7/100,000. Men accounted for 85.4% of all cases. The mean age of patients was 64.9 +/- 15.4 years. The majority of patients were occupationally exposed to asbestos (85.4%), 8.8% had environmental exposure, and 2.2% had domestic exposure. The type of household exposition was in 5.8% of patients. More than half of the cases were exposed to asbestos 31-40 years. The mean length of exposure was 28.87 +/- 15.63 years. The incidence of malignant pleural mesothelioma in Split-Dalmatian County has been obviously increasing due to the predominantly occupational exposure and it is reasonable to assume that it will remain high in the next two-three decades and to be a reason for concern and fear among the general population.}, } @article {pmid24281081, year = {2010}, author = {Tomasetti, M and Santarelli, L}, title = {Biomarkers for early detection of malignant mesothelioma: diagnostic and therapeutic application.}, journal = {Cancers}, volume = {2}, number = {2}, pages = {523-548}, pmid = {24281081}, issn = {2072-6694}, abstract = {Malignant mesothelioma (MM) is a rare and aggressive tumour of the serosal cavities linked to asbestos exposure. Improved detection methods for diagnosing this type of neoplastic disease are essential for an early and reliable diagnosis and treatment. Thus, focus has been placed on finding tumour markers for the non-invasive detection of MM. Recently, some blood biomarkers have been described as potential indicators of early and advanced MM cancers. The identification of tumour biomarkers alone or in combination could greatly facilitate the surveillance procedure for cohorts of subjects exposed to asbestos, a common phenomenon in several areas of western countries.}, } @article {pmid21475938, year = {2009}, author = {Schneider, J and Bernges, U}, title = {CYP1A1 and CYP1B1 polymorphisms as modifying factors in patients with pneumoconiosis and occupationally related tumours: A pilot study.}, journal = {Molecular medicine reports}, volume = {2}, number = {6}, pages = {1023-1028}, doi = {10.3892/mmr_00000209}, pmid = {21475938}, issn = {1791-3004}, abstract = {CYP1A1 and CYP1B1 are involved in the metabolism of carcinogens. The effect of CYP1A1 and CYP1B1 polymorphisms as genetic modifiers of risk was investigated in individuals with asbestos, silica dust or ionizing radiation-induced occupational tumours compared to exposed non-cancer subjects suffering from pneumoconiosis, particularly in relation to tobacco smoking. CYP1A1 T6235C, CYP1A1 A4889G and CYP1B1 codon 432 polymorphisms were determined by real-time PCR analysis in patients with asbestos-related lung cancer (n=39), patients with diffuse malignant mesotheliomas (n=19), lung cancer in silicosis patients (n=7), uranium miners with lung cancer (UMLC) (n=40), patients with asbestosis (n=181), and silicosis patients (n=204). The results were compared to those from a healthy unexposed control group (n=50) not exposed to carcinogenic (or fibrogenic) agents in the workplace. An additional healthy control group (n=134) comprised smokers and ex-smokers. Allele frequencies were within the range described for Caucasians. Multivariate analysis revealed that patients with occupational diseases with the susceptible CYP1A1 T6235C genotype had a calculated risk ranging from OR=0.5 (95% CI 0.18-1.36) for UMLC to OR=1.23 (95% CI 0.39-4.05) for uranium miners with silicosis. The risk for patients with the susceptible CYP1A1 A4889G allele was calculated as being between OR=0.39 (95% CI 0.10-1.54) for mesothelioma patients and OR=1.54 (95% CI 0.49-4.89) for UMLC. CYP1B1 Val432Leu polymorphisms were associated with a risk of OR=0.56 (95% CI 0.2-1.55) for UMLC and OR=1.52 (95% CI 0.68-3.39) for asbestos-exposed lung cancer patients. By analyzing the interaction between tobacco smoking, type of exposure to carcinogens and the genotypes, it was determined that smoking and the presence of the susceptible genotypes did not have a combined effect. In this pilot study, the analyzed polymorphism had no consistent modifying effect on pneumoconiosis or occupationally related tumours.}, } @article {pmid22505977, year = {2009}, author = {Yang, GZ and Li, J and Ding, HY}, title = {Localized malignant myxoid anaplastic mesothelioma of the pericardium.}, journal = {Journal of clinical medicine research}, volume = {1}, number = {2}, pages = {115-118}, pmid = {22505977}, issn = {1918-3003}, abstract = {UNLABELLED: Primary malignant mesothelioma of the pericardium is a rare cardiac neoplasm. Most are diffuse and have poor prognosis with median survival of six months. In the paper, we describe a young male patient having no exposure history of asbestos with localized malignant myxoid mesothelioma of the pericardium. The tumor displayed significant myxoid change in stroma, and anaplastic cytology, including pleomorphy, poor cohesion, prominent nuclei, with high mitoses, which led to difficulty in diagnosis. The tumor showed typical immunohistochemical phenotypes of mesothelioma, positive for WT-1, calretinin and CK5/6. Ki-67 labeling index was about 50% in general and nearly 80% in the most active areas. The patient showed better outcome. The report suggests the diagnosis of myxoid mesothelioma is supposed to rely on clinical data, and immunohistochemistry is assumed to be for differentiation.

KEYWORDS: Myxoid mesothelioma; Anaplastic; Diagnosis; Immunohistochemistry; Prognosis.}, } @article {pmid21475810, year = {2009}, author = {Suzuki, Y and Murakami, H and Kawaguchi, K and Tanigushi, T and Fujii, M and Shinjo, K and Kondo, Y and Osada, H and Shimokata, K and Horio, Y and Hasegawa, Y and Hida, T and Sekido, Y}, title = {Activation of the PI3K-AKT pathway in human malignant mesothelioma cells.}, journal = {Molecular medicine reports}, volume = {2}, number = {2}, pages = {181-188}, doi = {10.3892/mmr_00000081}, pmid = {21475810}, issn = {1791-2997}, abstract = {Malignant mesothelioma (MM) is a highly aggressive neoplasm, which is associated with asbestos exposure. The dysregulated phosphatidylinositol 3-kinase (PI3K)-AKT pathway plays an important role in cell proliferation, survival and motility in various cancers. In this study, we analyzed the activation status and underlying mechanisms of this pathway in MM cells using 21 cell lines. AKT activation was observed in 13 (62%) of the 21 MM cell lines under serum-starved conditions. Two cell lines, ACC-MESO-1 and Y-MESO-25, showed no expression of PTEN protein, while 7 other cell lines showed low expression of PTEN mRNA and protein compared to expression levels in an immortalized normal mesothelial cell line, MeT-5A. We found that PTEN inactivation in the ACC-MESO-1 and Y-MESO-25 lines was due to a 39.4-kb deletion including PTEN exon 2, and to a 7.7-kb deletion including exon 1, respectively. Re-expression of PTEN in these cells reduced the activity of colony formation in vitro. In contrast, no mutation of PIK3CA or LKB1 was found in any of the MM cell lines. These findings suggest that AKT is frequently activated in MM cells, in part due to the downregulation of PTEN. Thus, the PI3K-AKT signaling pathway is a potential therapeutic target for MM.}, } @article {pmid20740175, year = {2009}, author = {Nilsson, A and Rasmuson, T}, title = {Primary Pericardial Mesothelioma: Report of a Patient and Literature Review.}, journal = {Case reports in oncology}, volume = {2}, number = {2}, pages = {125-132}, pmid = {20740175}, issn = {1662-6575}, abstract = {Primary mesothelioma of the pericardium is a rare tumor and carries a dismal prognosis. This case report presents a 38-year-old man who suffered from recurrent pericardial fluid. Initial symptoms were unspecific, with dry cough and progressing fatigue. Pericardiocentesis was performed, but analyses for malignant cells and tuberculosis were negative. After recurrence a pericardiectomy was planned. At operation, partial resection of tumor tissue surrounding the heart was performed. Histopathologic examination including immunohistochemical staining for calretinin showed a biphasic mesothelioma. During the postoperative period the patient's condition ameliorated, but symptoms recurred and the patient died 3 months after diagnosis and 15 months after the first symptoms. At autopsy, the pericardium was transformed by the tumor that also expanded into the mediastinum and had set metastases to the liver. A review of 29 cases presented in the recent literature indicates a higher incidence of malignant pericardial mesothelioma among men than women. Median age was 46 (range, 19-76) years. In pleural mesotheliomas, exposure to asbestos is a known risk factor. However, in primary pericardial mesotheliomas the evidence for asbestos as an etiologic factor seems to be less convincing (3 exposed among 14 cases). Symptoms are often unspecific and cytologic examination of pericardial fluid is seldom conclusive (malignant cells demonstrated in 4/17 cases). Partial resection of the tumor can give a period of symptom reduction. Only a few patients have been treated with chemotherapy. Median survival of patients with pericardial mesotheliomas is approximately 6 months.}, } @article {pmid20192569, year = {2009}, author = {Tsuda, H and Xu, J and Sakai, Y and Futakuchi, M and Fukamachi, K}, title = {Toxicology of engineered nanomaterials - a review of carcinogenic potential.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {10}, number = {6}, pages = {975-980}, pmid = {20192569}, issn = {2476-762X}, mesh = {Animals ; Carcinogens/*toxicity ; Environmental Exposure/adverse effects ; Foreign-Body Reaction/chemically induced ; Fullerenes/toxicity ; Inhalation Exposure/adverse effects ; Mice ; Nanostructures/*toxicity ; *Nanotechnology ; Neoplasms/*chemically induced ; Rats ; Risk Assessment ; Soot/toxicity ; Titanium/toxicity ; }, abstract = {Nanotechnology has considerable socioeconomic potential. Benefits afforded by engineered nanoparticles (NP: defined as being less than 100 nm in diameter) are expected to be significant in fields such as plastics, energy, electronics, aerospace and medicine. However, NPs are being introduced into the market without adequate assessment of their potential toxicities. It is urgently important to conduct risk assessment of commercial NPs and establish a framework enabling risk management which is not subordinate to their commercial production. An overview of currently available carcinogenicity risk evaluation results of NP materials raises serious questions as to their safety. NP sized titanium dioxide (nTiO(2)) and carbon black (nCB) are carcinogenic to the lung of female rats, and the tumors preferentially include squamous cell morphology. Carbon nanotubes (CNT) induce mesotheliomas when applied intraperitoneally in rats and mice. Data for Fullerenes are insufficient to evaluate carcinogenic risk. Sub-chronic toxicity data indicate that, in general, NPs form aggregates and agglomerates and cause foreign body reactions at their applied sites with inflammatory cell, including macrophage, infiltration. These findings are similar to the biological effects of asbestos, a potent carcinogen, and indicate that careful assessment of NPs is indispensable.}, } @article {pmid20424652, year = {2008}, author = {Azim, HA and Gaafar, R and Abdel Salam, I and El-Guindy, S and Elattar, I and Ashmawy, A and Khorshid, O}, title = {Soluble mesothelin-related protein in malignant pleural mesothelioma.}, journal = {Journal of the Egyptian National Cancer Institute}, volume = {20}, number = {3}, pages = {224-229}, pmid = {20424652}, issn = {1110-0362}, abstract = {BACKGROUND AND PURPOSE: Building-up evidence suggests that soluble mesothelinrelated protein (SMRP) carries a diagnostic and a prognostic value in malignant pleural mesothelioma (MPM). Egypt suffers endemic asbestosis and thus this study was conducted to evaluate the sensitivity and specificity of SMRP in patients with MPM and to correlate this marker with known clinicopathological prognostic factors.

MATERIAL AND METHODS: During the period from January 2006 till March 2008, Serum samples were obtained from MPM patients presenting to the Egyptian National Cancer Institute, Cairo University. Serum samples were provided from patients with breast cancer and from healthy individuals to function as controls. The SMRP was assayed using the ELISA technique and correlations were made with different clinico-pathological prognostic parameters.

RESULTS: 83 patients (50 MPM and 33 breast cancer) as well as 22 healthy individuals were enrolled in this study. Serum SMRP levels were not different between patients with breast cancer and healthy controls (p > 0.05). However, there was a significant difference between MPM patients and the other two groups (p < 0.0001). ROC analysis showed an AUC = 0.765 for differentiating between the controls and MPM with a best statistical cut-off of 7.22nM/L (sensitivity = 66 % , specificity = 70.9 %). The mean SMRP concentrations were significantly higher in patients with advanced disease (p = 0.038), poor performance status (p = 0.017) and high alkaline phosphatase (p = 0.015). The mean SMRP concentrations were also higher in males, elderly patients, asbestos-exposed patients, epithelioid subtypes and patients with high platelet and leucocytic counts. However, these differences did not reach statistical significance

CONCLUSIONS: This study confirms that SMRP is of considerable sensitivity and specificity in Egyptian patients with MPM. Higher levels are frequently seen in patients with high tumor burden, which could be helpful in monitoring response to therapy.

KEY WORDS: Malignant pleural mesothelioma (MPM) - Soluble mesothelin related protein (SMRP)- Sensitivity - Specificity - Asbestos.}, } @article {pmid25967566, year = {2008}, author = {Parente, B}, title = {Mesothelioma treatment.}, journal = {Revista portuguesa de pneumologia}, volume = {14 Suppl 2}, number = {}, pages = {S35-44}, doi = {10.1016/S0873-2159(15)30313-5}, pmid = {25967566}, issn = {0873-2159}, abstract = {Malignant mesothelioma (MM) is a locally aggressive advanced tumour, with bad prognosis and many times fatal, who have been growing in the last two decades with possibilities to be continue in all the world until 2020, showing use of pic asbestos to the years 1960/1970. Next 35 years the previsions of the deaths is more than 250 000. In Portugal (ROR) incidence is 1,2/1 000 000/year for total of the patients. Until now any new therapy showed advantage in the median survival and time to progression. The more important change whose the news than the antifolatos, particularly pemetrexed in combination with cisplatinum were actives in MM. Chemoterapy as soon as possible and second lines treatment it is very important thinking in the survival this fatal tumor. Rev Port Pneumol 2008; XIV (Sup.2): S35-S44.}, } @article {pmid21157517, year = {2008}, author = {Maeda, M and Miura, Y and Nishimura, Y and Murakami, S and Hayashi, H and Kumagai, N and Hatayama, T and Katoh, M and Miyahara, N and Yamamoto, S and Fukuoka, K and Kishimoto, T and Nakano, T and Otsuki, T}, title = {Immunological changes in mesothelioma patients and their experimental detection.}, journal = {Clinical medicine. Circulatory, respiratory and pulmonary medicine}, volume = {2}, number = {}, pages = {11-17}, pmid = {21157517}, issn = {1178-1157}, abstract = {It is common knowledge that asbestos exposure causes asbestos-related diseases such as asbestosis, lung cancer and malignant mesothelioma (MM) not only in people who have handled asbestos in the work environment, but also in residents living near factories that handle asbestos. These facts have been an enormous medical and social problem in Japan since the summer of 2005. We focused on the immunological effects of asbestos and silica on the human immune system. In this brief review, we present immunological changes in patients with MM and outline their experimental detection. For example, there is over-expression of bcl-2 in CD4+ peripheral T-cells, high plasma concentrations of interleukin (IL)-10 and transforming growth factor (TGF)-ß, and multiple over-representation of T cell receptor (TcR)-Vß in peripheral CD3+ T-cells found in MM patients. We also detail an experimental long-term exposure T-cell model. Analysis of the immunological effects of asbestos may help our understanding of the biological effects of asbestos.}, } @article {pmid20396658, year = {2008}, author = {Kant, S and Verma, SK and Sanjay, }, title = {Malignant pleural mesothelioma without asbestos exposure with distant metastasis in a peripheral lymph node: a case report.}, journal = {Lung India : official organ of Indian Chest Society}, volume = {25}, number = {1}, pages = {31-33}, pmid = {20396658}, issn = {0974-598X}, abstract = {Malignant mesothelioma is an uncommon pleural neoplasm and usually associated with inhalation exposure to asbestos. About 20% of the patients have no demonstrable exposure to asbestos. It rarely metastasizes in peripheral lymph nodes. Here is a case report of malignant pleural mesothelioma without asbestos exposure with cervical lymph node metastasis.}, } @article {pmid21552981, year = {1995}, author = {Mikulski, S}, title = {Treatment of malignant mesothelioma (review).}, journal = {International journal of oncology}, volume = {7}, number = {6}, pages = {1415-1420}, doi = {10.3892/ijo.7.6.1415}, pmid = {21552981}, issn = {1019-6439}, abstract = {Malignant mesothelioma (MM) has a very variable natural history. Its known relationship to asbestos exposure is often difficult to establish in a particular patient in view of a long preceding latency period of up to 40+ years. Survival depends on several prognostic factors including histological type, stage, performance status, resectability, and response to radiation and chemotherapy (CT). The assessment of the therapeutic impact on survival is usually difficult due to the different treatment philosophies and selections of patients in various clinical trials. Combined modality treatment approaches seem to offer the best outcomes, with occasional long-term disease-free survivors. Unresectable MM presents a difficult therapeutic challenge. In patients treated with systemic CT the median survival time (MST) in the range of 6 to 12 months and the 2 year survival of <20% are typical. The MST in excess of 20 months and the 2 year survival in the range of 40% have been reported in a few multimodality therapy trials in patients with at least partially resectable MM. Despite some encouraging therapeutic results in selected patients, the overall response to treatment(s) remains unsatisfactory, and new treatments must be sought.}, } @article {pmid21539476, year = {1995}, author = {Mast, RW and McConnell, EE and Anderson, R and Chevalier, J and Kotin, P and Bernstein, DM and Thevenaz, P and Glass, LR and Miiller, WC and Hesterberg, TW}, title = {Studies on the chronic toxicity (inhalation) of four types of refractory ceramic fiber in male Fischer 344 rats.}, journal = {Inhalation toxicology}, volume = {7}, number = {4}, pages = {425-467}, doi = {10.3109/08958379509015208}, pmid = {21539476}, issn = {0895-8378}, abstract = {Abstract Refractory ceramic fibers (RCF) are man-made vitreous fibers used primarily in industrial high-temperature applications, especially for insulation of furnaces and kilns. Because of their increasing use and potential for human exposure, a chronic toxicity/carcinogenicity inhalation study was conducted in Fischer 344 (F344) rats. Five groups of 140 weanling male F344 rats were exposed via noseonly inhalation to either HEPA-filtered air (chamber controls) or 30 mg/m(3) (approximately 220 fibers/cm(3)) of three types [kaolin-based, high-purity, and aluminum zirconia silica (AZS)] of "size-selected" RCF fibers (approximately 1µ in diameter and approximately 20 um in length) and an "after-service" heat-treated (2400°F for 24 h) kaolin-based fiber for 6 h/day, 5 days/wk for 24 mo. They were then held unexposed until approximately 20% survival and then sacrificed at 30 mo. A positive control group of 80 F344 rats was exposed to 10 mg/m(3) chrysotile asbestos. Croups of 3-6 animals were sacrificed at 3, 6, 9, 12, 15, 18, and 24 mo to follow the progression of lesions and to determine fiber lung burdens. Additional groups of 3 rats were removed from exposure at 3, 6, 9, 12, and 18 mo and were held until sacrificed at 24 mo (recovery groups) for similar determinations. Lung burdens increased rapidly for all RCFs, appearing to plateau by about 12 mo. By 24 mo, lung burdens ranged from 2.6 to 9.6 × 10(5) fiberslmg of dry lung tissue for the RCFs tested. Treatment-related lesions were restricted to the lungs. To some extent all types of RCF resulted in macrophage infiltration, bronchiolization of proximal alveoli, and microgranuloma formation by 3 mo of exposure. Interstitial fibrosis was observed at 6 mo for all types of RCF, except the "after-service" fiber where fibrosis was not seen until 12 mo. The lesions progressed in severity until 12-15 mo, after which they plateaued. A minimal amount of focal pleural fibrosis was first observed at 9 mo and progressed to a mild severity by the end of the study. Fxposure-related pulmonary neoplasms (bronchoalveolar adenomas and carcinomas combined) were observed with all 4 types of RCF [kaolin, 16 of 123 (13%); AZS, 9 of 121 (7.4%); high-purity, 19 of 121 (15.7%); and "after-service,"4 of 118 (3.4%)], compared to 2 of 120 (1.5%) in the untreated air controls. Pleural mesotheliomas were observed in two kaolin, three AZS, two high-purity, and one "after-service" exposed rats. A comparable but slightly greater amount of fibrosis was observed in the lungs of the positive (chrysotile asbestos) controls. The incidence of bronchoalveolar neoplasms in the chrysotile exposed rats was 13 of 69 (18.8%), and a mesothelioma occurred in 1 (1.4%) animal. The results of this study showed that the four types of RCF studied had carcinogenic activity in rats at the maximum tolerated dose.}, } @article {pmid20120584, year = {1981}, author = {Gylseth, B and Baunan, R}, title = {Topographic and size distribution of asbestos bodies in exposed human lungs.}, journal = {Scandinavian journal of work, environment & health}, volume = {7}, number = {3}, pages = {190-195}, doi = {10.5271/sjweh.3111}, pmid = {20120584}, issn = {0355-3140}, mesh = {Asbestos/adverse effects/*analysis ; Asbestos, Amphibole/analysis ; Asbestos, Serpentine/analysis ; Humans ; Lung/*pathology ; Lung Neoplasms/etiology/*pathology ; Male ; Mesothelioma/etiology/*pathology ; Microscopy, Electron, Scanning ; Mineral Fibers/adverse effects/analysis ; Specimen Handling/methods ; }, abstract = {The concentration and the length distribution of asbestos bodies in exposed human lungs have been determined in autopsy material by scanning electron microscopy after two different methods for preparing the tissue samples. The results demonstrate that the number of bodies vary between the right and left lung, as well as between the different lobes of a lung. The length distribution between the different lungs was, on the average, more or less the same; however small differences occurred between the different lobes. It was further shown that drying the tissue pieces before the analyses affected both the number and the length of the bodies. Examples of different types of asbestos bodies are presented, and their possible biological activity is discussed.}, } @article {pmid20120583, year = {1981}, author = {Hilt, B and Rosenberg, J and Langård, S}, title = {Occurrence of cancer in a small cohort of asbestos-exposed workers.}, journal = {Scandinavian journal of work, environment & health}, volume = {7}, number = {3}, pages = {185-189}, doi = {10.5271/sjweh.3110}, pmid = {20120583}, issn = {0355-3140}, mesh = {Adult ; Asbestos/*adverse effects ; Humans ; Incidence ; Lung Neoplasms/diagnostic imaging/epidemiology/*etiology ; Male ; Mesothelioma/diagnostic imaging/epidemiology/etiology ; Mineral Fibers/adverse effects ; Neoplasms/diagnostic imaging/epidemiology/*etiology ; Norway/epidemiology ; Occupational Exposure/*adverse effects ; Radiography ; }, abstract = {During the construction period of a saltpeter plant from 1928 through 1929, 21 young men of equal age were heavily exposed to asbestos dust for 1 a. During an observation period from 1 January 1943 to 30 June 1980 three cases of lung cancer and two cases of mesothelioma were observed in the cohort. The number of lung cancers to be expected was 0.21. Radiographic changes associated with asbestos exposure were present in 17 of the 18 available chest radiographs.}, } @article {pmid22283003, year = {1980}, author = {Gormley, IP and Bolton, RE and Brown, G and Davis, JM and Donaldson, K}, title = {Studies on the morphological patterns of asbestos induced mesotheliomas in vivo and in vitro.}, journal = {Carcinogenesis}, volume = {1}, number = {3}, pages = {219-231}, doi = {10.1093/carcin/1.3.219}, pmid = {22283003}, issn = {0143-3334}, mesh = {Animals ; Asbestos, Crocidolite/*toxicity ; In Vitro Techniques ; Male ; Mesothelioma/*chemically induced/*pathology ; Mice ; Mice, Nude ; Peritoneal Neoplasms/*chemically induced/*pathology ; Rats ; Rats, Wistar ; Tumor Cells, Cultured ; }, abstract = {Cell lines were established in vitro from five peritoneal mesotheliomas produced in rats by the injection of crocidolite asbestos. These tumours exhibited the previously described diverse range of histological patterns normally associated with mesotheliomas. This diversity of appearance was also evident in culture but cell patterns in vitro did not necessarily correspond to the histology of the original tumour. With increased time in culture most cell lines tended towards a pattern of random orientation associated with the piling up of cells to form discrete masses. Despite this variation in cell pattern in culture, few ultrastructural differences were seen during electron microscope examination. Following varying periods in culture, some cell lines from these tumours were injected into either rats or athymic mice. Only one typical rat mesothelioma was produced but all cell lines produced tumours in athymic mice. The implications of these findings are discussed in relation to the aetiology of asbestos induced mesotheliomas.}, } @article {pmid20918862, year = {1966}, author = {O'B Hourihane, D}, title = {Asbestos and mesothelioma of the pleura [abridged].}, journal = {Proceedings of the Royal Society of Medicine}, volume = {59}, number = {1}, pages = {60}, pmid = {20918862}, issn = {0035-9157}, } @article {pmid20918861, year = {1966}, author = {Newhouse, M}, title = {Asbestos and mesothelioma of the pleura [abridged].}, journal = {Proceedings of the Royal Society of Medicine}, volume = {59}, number = {1}, pages = {60-61}, pmid = {20918861}, issn = {0035-9157}, } @article {pmid20100205, year = {2010}, author = {Inami, K and Abe, M and Takeda, K and Hagiwara, Y and Maeda, M and Segawa, T and Suyama, M and Watanabe, S and Hino, O}, title = {Antitumor activity of anti-C-ERC/mesothelin monoclonal antibody in vivo.}, journal = {Cancer science}, volume = {101}, number = {4}, pages = {969-974}, pmid = {20100205}, issn = {1349-7006}, mesh = {Animals ; Antibodies, Monoclonal/immunology/pharmacology/*therapeutic use ; Antibody-Dependent Cell Cytotoxicity/drug effects/immunology ; Female ; GPI-Linked Proteins ; Humans ; Killer Cells, Natural/immunology/metabolism ; Membrane Glycoproteins/*immunology ; Mesothelin ; Mesothelioma/*therapy ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Oncogene Proteins/immunology ; }, abstract = {Mesothelioma is an aggressive cancer often caused by chronic asbestos exposure, and its prognosis is very poor despite the therapies currently used. Due to the long latency period between asbestos exposure and tumor development, the worldwide incidence will increase substantially in the next decades. Thus, novel effective therapies are warranted to improve the prognosis. The ERC/mesothelin gene (MSLN) is expressed in wide variety of human cancers, including mesotheliomas, and encodes a precursor protein cleaved by proteases to generate C-ERC/mesothelin and N-ERC/mesothelin. In this study, we investigated the antitumor activity of C-ERC/mesothelin-specific mouse monoclonal antibody, 22A31, against tumors derived from a human mesothelioma cell line, ACC-MESO-4, in a xenograft experimental model using female BALB/c athymic nude mice. Treatment with 22A31 did not inhibit cell proliferation of ACC-MESO-4 in vitro; however, therapeutic treatment with 22A31 drastically inhibited tumor growth in vivo. 22A31 induced antibody-dependent cell-mediated cytotoxicity by natural killer (NK) cells, but not macrophages, in vitro. Consistently, the F(ab')(2) fragment of 22A31 did not inhibit tumor growth in vivo, nor did it induce antibody-dependent cell mediated cytotoxicity (ADCC) in vitro. Moreover, NK cell depletion diminished the antitumor effect of 22A31. Thus, 22A31 induced NK cell-mediated ADCC and exerted antitumor activity in vivo. 22A31 could have potential as a therapeutic tool to treat C-ERC/mesothelin-expressing cancers including mesothelioma.}, } @article {pmid20092958, year = {2010}, author = {Goldstein, R and Hasleton, PS}, title = {Survey of British pathologists' performance of mesothelioma post-mortems.}, journal = {Pathology, research and practice}, volume = {206}, number = {3}, pages = {174-179}, doi = {10.1016/j.prp.2009.11.002}, pmid = {20092958}, issn = {1618-0631}, mesh = {Autopsy/*statistics & numerical data ; Biomarkers, Tumor/analysis ; Diagnosis ; Humans ; Immunohistochemistry ; Lung Neoplasms/*diagnosis ; Mesothelioma/*diagnosis/metabolism ; Pathology/*statistics & numerical data ; Pleural Neoplasms/*diagnosis ; Surveys and Questionnaires ; United Kingdom ; }, abstract = {We analyzed the practice of mesothelioma post-mortems in the United Kingdom (UK). Between 2003 and 2004, a questionnaire was sent to all UK Consultant Histopathologists, and 12% were recruited. In general post-mortems, the Coroner approved 60% of requests for organ retention, and Pathologists failed to make such a request in 5.9% of cases. In asbestos cases, the lungs were not fixed for sampling in 54.8% of cases, owing to the Coroners' refusal in 46.4% and the pathologists' failure to make a request in 8.4% of cases. In epithelioid mesothelioma, mesothelial and epithelial stains were considered to be of similar importance, and calretinin was the most popular individual stain. In sarcomatoid mesothelioma, mesothelial stains were chosen by 45.9% of pathologists, cytokeratin by 18.7% and epithelial stains by 18.5%. Calretinin was the most popular stain. Accurate mesothelioma diagnosis is impeded by the lack of tissue being made available by the Coroner and failure of some pathologists to make requests. Pathologists use appropriate immunohistochemical testing in epithelioid mesothelioma. In sarcomatoid mesothelioma, epithelioid stains were popular but have limited use. The Coroner should approve more requests for organ retention, and information should be disseminated to pathologists regarding best practice in mesothelioma.}, } @article {pmid20089367, year = {2010}, author = {Dainese, E and Pozzi, B and Milani, M and Rossi, G and Pezzotta, MG and Vertemati, G and Tricomi, P and Sessa, F}, title = {Primary pleural epithelioid angiosarcoma. A case report and review of the literature.}, journal = {Pathology, research and practice}, volume = {206}, number = {6}, pages = {415-419}, doi = {10.1016/j.prp.2009.11.008}, pmid = {20089367}, issn = {1618-0631}, mesh = {Biomarkers, Tumor/analysis ; Diabetes Mellitus, Type 2 ; Diagnosis, Differential ; Female ; Hemangiosarcoma/*pathology/physiopathology/surgery ; Humans ; Immunohistochemistry ; Lung Neoplasms/*pathology/physiopathology/surgery ; Male ; Mesothelioma/pathology ; Middle Aged ; Neoplasm Metastasis/pathology ; Radiculopathy/complications ; }, abstract = {Malignant vascular tumors are uncommon sarcomas that arise from endothelial cells of small blood vessels and may affect every organ. Pleural localization is very exceptional, and only 48 cases have been reported in the English literature to date. Even if etiological factors implicated in the development of vascular sarcomas are still unclear, the strongest association with the disease was a history of chronic tuberculous pyothorax, observed only in Japanese patients, while prior radiotherapy and occupational exposure to asbestos have been reported in few Western cases. The mean age at diagnosis was 58 years, and the male to female ratio was 6:1. The overall prognosis was poor, and most of the patients died of disease soon after diagnosis. Histological features and clinical presentation often cause several problems in the differential diagnosis, particularly with mesothelioma and metastasis from poorly differentiated carcinomas. Immunohistochemistry plays an important role in identifying these rare entities, confirming the endothelial origin of the neoplasm with the expression of at least one of the vascular markers CD31, CD34, or factor VIII-related antigen. We report herein a further case of a 62-year-old man who presented with progressive dyspnea and bilateral massive hemothorax. The overall pathological and immunohistochemical features of the pleural specimens supported the diagnosis of epithelioid angiosarcoma.}, } @article {pmid20088796, year = {2010}, author = {Crispi, S and Cardillo, I and Spugnini, EP and Citro, G and Menegozzo, S and Baldi, A}, title = {Biological agents involved in malignant mesothelioma: relevance as biomarkers or therapeutic targets.}, journal = {Current cancer drug targets}, volume = {10}, number = {1}, pages = {19-26}, doi = {10.2174/156800910790980232}, pmid = {20088796}, issn = {1873-5576}, mesh = {Animals ; Asbestos/toxicity ; Biomarkers, Tumor/analysis/*genetics ; Carcinogens/toxicity ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/chemically induced/diagnosis/drug therapy/genetics ; *Mesothelioma/chemically induced/diagnosis/drug therapy/genetics ; Mice ; Mutation ; *Peritoneal Neoplasms/chemically induced/diagnosis/drug therapy/genetics ; *Pleural Neoplasms/chemically induced/diagnosis/drug therapy/genetics ; }, abstract = {Malignant mesothelioma (MM) is a rare, highly aggressive tumor that arises from the surface serosal cells (pleural, peritoneal and pericardial cavities). Epidemiological and clinical data show that there is an association between asbestos exposure and MM development, even if the exact mechanism whereby asbestos induces MM is unknown. The continuing identification and elucidation of the molecular defects involved in mesothelioma pathogenesis and progression should lead to better disease control and greater therapeutic options in the near future. Goal of this article is to summarize the most recent advances in molecular pathogenesis of mesothelioma with particular emphasis on genes that could be considered as biomarkers or therapeutic targets and discuss possible clinical implications of these findings.}, } @article {pmid20085481, year = {2010}, author = {Berman, DW}, title = {Comparing milled fiber, Quebec ore, and textile factory dust: has another piece of the asbestos puzzle fallen into place?.}, journal = {Critical reviews in toxicology}, volume = {40}, number = {2}, pages = {151-188}, doi = {10.3109/10408440903349137}, pmid = {20085481}, issn = {1547-6898}, mesh = {Air Pollutants, Occupational/*analysis ; Asbestos/*analysis ; Dust/*analysis ; Environmental Exposure/*analysis ; Humans ; Lung Neoplasms/epidemiology/etiology ; Mesothelioma/epidemiology/etiology ; Microscopy, Electron, Transmission ; Microscopy, Phase-Contrast ; Mineral Fibers/analysis ; Mining ; Particle Size ; Risk Assessment ; Textiles ; }, abstract = {Results of a meta-analysis indicate that the variation in potency factors observed across published epidemiology studies can be substantially reconciled (especially for mesothelioma) by considering the effects of fiber size and mineral type, but that better characterization of historical exposures is needed before improved exposure metrics potentially capable of fully reconciling the disparate potency factors can be evaluated. Therefore, an approach for better characterizing historical exposures, the Modified Elutriator Method (MEM), was evaluated to determine the degree that dusts elutriated using this method adequately mimic dusts generated by processing in a factory. To evaluate this approach, elutriated dusts from Grade 3 milled fiber (the predominant feedstock used at a South Carolina [SC] textile factory) were compared to factory dust collected at the same facility. Elutriated dusts from chrysotile ore were also compared to dusts collected in Quebec mines and mills. Results indicate that despite the substantial variation within each sample set, elutriated dusts from Grade 3 fiber compare favorably to textile dusts and elutriated ore dusts compare to dusts from mines and mills. Given this performance, the MEM was also applied to address the disparity in lung cancer mortality per unit of exposure observed, respectively, among chrysotile miners/millers in Quebec and SC textile workers. Thus, dusts generated by elutriation of stockpiled chrysotile ore (representing mine exposures) and Grade 3 milled fiber (representing textile exposures) were compared. Results indicate that dusts from each sample differ from one another. Despite such variation, however, the dusts are distinct and fibers in Grade 3 dusts are significantly longer than fibers in ore dusts. Moreover, phase-contrast microscopy (PCM) structures in Grade 3 dusts are 100% asbestos and counts of PCM-sized structures are identical, whether viewed by PCM or transmission electron microscope (TEM). In contrast, a third of PCM structures in ore dusts are not asbestos and only a third that are counted by PCM are also counted by TEM. These distinctions also mirror the characteristics of the bulk materials themselves. Perhaps most important, when the differences in size distributions and PCM/TEM distinctions in these dusts are combined, the combined difference is sufficient to completely explain the difference in exposure/response observed between the textile worker and miner/miller cohorts. Importantly, however, evidence that such an explanation is valid can only be derived from a meta-analysis (risk assessment) covering a diverse range of epidemiology study environments, which is beyond the scope of the current study. The above findings suggest that elutriator-generated dusts mimic factory dusts with sufficient reliability to support comparisons between historical exposures experienced by the various cohorts studied by epidemiologists. A simulation was also conducted to evaluate the relative degree that the characteristics of dust are driven by the properties of the bulk material processed versus the nature of the mechanical forces applied. That results indicate it is the properties of bulk materials reinforces the theoretical basis justifying use of the elutriator to reconstruct historical exposures. Thus, the elutriator may be a valuable tool for reconstructing historical exposures suitable for supporting continued refinements of the risk models being developed to predict asbestos-related cancer risk.}, } @article {pmid20081811, year = {2010}, author = {Klebe, S and Brownlee, NA and Mahar, A and Burchette, JL and Sporn, TA and Vollmer, RT and Roggli, VL}, title = {Sarcomatoid mesothelioma: a clinical-pathologic correlation of 326 cases.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {23}, number = {3}, pages = {470-479}, doi = {10.1038/modpathol.2009.180}, pmid = {20081811}, issn = {1530-0285}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/analysis ; Asbestosis/complications/metabolism/pathology ; Biomarkers, Tumor/metabolism ; Female ; Humans ; Lung/chemistry/pathology ; Male ; Mesothelioma/etiology/metabolism/*pathology ; Middle Aged ; Mineral Fibers ; Peritoneal Neoplasms/etiology/metabolism/*pathology ; Pleural Neoplasms/etiology/metabolism/*pathology ; Sarcoma/etiology/metabolism/*pathology ; }, abstract = {Sarcomatoid mesothelioma is the least common, but most aggressive of the three major histological types of mesotheliomas. This study comprises 326 cases of sarcomatoid mesotheliomas among 2000 consecutive malignant mesothelioma cases received in consultation (16%). Patients included 312 men (96%) and 14 women (4%), with a median age of 70 years (range 41-94 years). Most tumors were pleural (319; 98%), and 7 were peritoneal (2%). Some desmoplastic features were identified in 110 cases (34%), and 70 (21%) were classified as desmoplastic. Rare subtypes included two cases with a lymphohistiocytoid pattern (<1%) and eight heterologous mesotheliomas (2%). Labeling for cytokeratins (CKs) was observed in 261/280 cases (93%), and for calretinin and vimentin in 31 and 91%, respectively. Pleural plaques were present in 79% of cases for which information was available, and asbestosis was diagnosed in 34/127 cases (27%). Median survival was 3.5 months. Fiber analysis was performed in 61 cases. The median asbestos body count was 1640/g wet lung tissue (by light microscopy). Amosite fibers were the most commonly identified fibers using energy-dispersive X-ray analysis and were significantly higher in the sarcomatoid cases, as were uncoated fibers using scanning electron microscopy. This study represents the largest series of sarcomatoid and desmoplastic malignant mesotheliomas to date and confirms the diagnostic usefulness of CK immunohistochemistry. The relationship with asbestos exposure--particularly amosite--and an association with pleural plaques and less often asbestosis is confirmed.}, } @article {pmid20081810, year = {2010}, author = {Krasinskas, AM and Bartlett, DL and Cieply, K and Dacic, S}, title = {CDKN2A and MTAP deletions in peritoneal mesotheliomas are correlated with loss of p16 protein expression and poor survival.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {23}, number = {4}, pages = {531-538}, doi = {10.1038/modpathol.2009.186}, pmid = {20081810}, issn = {1530-0285}, mesh = {Adult ; Aged ; Cyclin-Dependent Kinase Inhibitor p16/*biosynthesis ; Female ; Gene Deletion ; *Genes, p16 ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Kaplan-Meier Estimate ; Male ; Mesothelioma/*genetics/metabolism/mortality ; Middle Aged ; Peritoneal Neoplasms/*genetics/metabolism/mortality ; Purine-Nucleoside Phosphorylase/*genetics ; Tissue Array Analysis ; Young Adult ; }, abstract = {Homozygous deletion of CDKN2A (p16) is one of the most common genetic alterations in pleural mesotheliomas, occurring in up to 74% of cases. MTAP resides in the same gene cluster of the 9p21 region and is co-deleted in the majority of CDKN2A deleted cases. This study examines the genetic alterations in peritoneal mesotheliomas, which may have a different pathogenesis than their pleural counterparts. Twenty-six cases of peritoneal mesotheliomas in a triplicate tissue microarray were studied. Dual-color fluorescence in situ hybridization was performed with CDKN2A and MTAP locus-specific probes. Nine of 26 (35%) peritoneal mesotheliomas had homozygous deletion of CDKN2A; MTAP was co-deleted in every case. All cases with CDKN2A deletions had loss of p16 protein expression; five cases had loss of p16 protein without evidence of CDKN2A deletions. All patients with CDKN2A deletions were men (P, NS) and were significantly older (mean, 63 years) than the patients with no deletions (mean, 52 years) (P=0.033, t-test). An association with asbestos exposure could not be proved in this study. Similar to pleural mesotheliomas, patients with CDKN2A deletions and loss of p16 protein expression had worse overall and disease-specific survival (P=0.010 and 0.006, respectively; Kaplan-Meier log rank). Detection of CDKN2A-MTAP co-deletion in peritoneal mesotheliomas, coupled with a p16 immunohistochemical stain as an inexpensive screening tool, can help identify those patients who may have an unfavorable outcome after aggressive cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy and those who may respond to targeted therapy of the MTAP pathway.}, } @article {pmid20077199, year = {2009}, author = {Han, JH and Park, JD and Sakai, K and Hisanaga, N and Chang, HK and Lee, YH and Kwon, IH and Choi, BS and Chung, YH and Kim, HY and Yang, JS and Cho, MH and Yu, IJ}, title = {Comparison of lung asbestos fiber content in cancer subjects with healthy individuals with no known history of occupational asbestos exposure in Korea.}, journal = {Journal of toxicology and environmental health. Part A}, volume = {72}, number = {21-22}, pages = {1292-1295}, doi = {10.1080/15287390903212345}, pmid = {20077199}, issn = {1528-7394}, mesh = {Adolescent ; Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Asbestos/*isolation & purification/*toxicity ; Case-Control Studies ; Female ; Humans ; Lung/chemistry ; Lung Neoplasms/*chemically induced/epidemiology ; Male ; Mesothelioma/*chemically induced/epidemiology ; Middle Aged ; Occupational Exposure ; Republic of Korea/epidemiology ; Young Adult ; }, abstract = {To evaluate the effects of environmental asbestos exposure on the inducement of lung cancer, pulmonary asbestos and non-asbestos fiber content was determined in 36 normal Korean subjects and 38 lung cancer subjects with no known occupational history of asbestos exposure. Pulmonary asbestos fiber content was measured by transmission electron microscopy (TEM) with energy-dispersive x-ray analysis after applying a low-temperature ashing procedure. Chrysotile fibers were the major fiber type found in the lungs of the Korean subjects. The asbestos fiber concentrations found in the lungs of normal males (25) and females (11) were 0.26 x 10(6) fibers/g of dry lung tissue and 0.16 x 10(6) fibers/g of dry lung tissue, respectively. The asbestos concentrations found in the lungs of cancer subjects were 0.16 x 10(6) fibers/g of dry lung tissue for 32 males and 0.44 x 10(6) fibers/g of dry lung tissue for 6 females. No statistical difference was found in pulmonary asbestos content between the normal and lung cancer subjects, whereas a statistical difference was noted between normal and lung cancer subjects with respect to lung non-asbestos content, indicating a potential role for non-asbestos fibers being associated with lung cancer.}, } @article {pmid20075387, year = {2010}, author = {Hollevoet, K and Nackaerts, K and Thimpont, J and Germonpré, P and Bosquée, L and De Vuyst, P and Legrand, C and Kellen, E and Kishi, Y and Delanghe, JR and van Meerbeeck, JP}, title = {Diagnostic performance of soluble mesothelin and megakaryocyte potentiating factor in mesothelioma.}, journal = {American journal of respiratory and critical care medicine}, volume = {181}, number = {6}, pages = {620-625}, doi = {10.1164/rccm.200907-1020OC}, pmid = {20075387}, issn = {1535-4970}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Area Under Curve ; Biomarkers, Tumor/*blood ; Cohort Studies ; Enzyme-Linked Immunosorbent Assay/methods ; Female ; GPI-Linked Proteins ; Humans ; Male ; Membrane Glycoproteins/*blood ; Mesothelin ; Mesothelioma/*blood/*diagnosis ; Middle Aged ; Pleural Neoplasms/*blood ; Prospective Studies ; Reproducibility of Results ; Sensitivity and Specificity ; Young Adult ; }, abstract = {RATIONALE: Soluble mesothelin (SM) is currently the reference serum biomarker of malignant pleural mesothelioma (MPM). Megakaryocyte potentiating factor (MPF), which originates from the same precursor protein, is potentially more sensitive, yet lacks validation.

OBJECTIVES: To analyze the diagnostic performance of MPF as an MPM biomarker and compare this performance with SM.

METHODS: A total of 507 participants were enrolled in six cohorts: healthy control subjects (n = 101), healthy asbestos-exposed individuals (n = 89), and patients with benign asbestos-related disease (n = 123), benign respiratory disease (n = 46), lung cancer (n = 63), and MPM (n = 85). Sera were analyzed for SM and MPF levels using the Mesomark and Human MPF ELISA kit, respectively.

MEASUREMENTS AND MAIN RESULTS: SM and MPF levels differed significantly between patients with MPM and participants from each other cohort (P < 0.001). Receiver operating characteristics curve analysis did not reveal a significant difference between both markers in area under curve (AUC) for distinguishing MPM from all cohorts jointly (SM = 0.871, MPF = 0.849; P = 0.28). At 95% specificity, SM and MPF had a sensitivity of 64% (cutoff = 2.00 nmol/L) and 68% (cutoff = 12.38 ng/ml), respectively. Combining both markers did not improve the diagnostic performance.

CONCLUSIONS: In this prospective multicenter study, MPF is validated as a highly performant MPM biomarker. The similar AUC values of SM and MPF, together with the limited difference in sensitivity, show that both serum biomarkers have an equivalent diagnostic performance.}, } @article {pmid20075037, year = {2010}, author = {Hoffmann, M and Bruch, HP and Kujath, P and Limmer, S}, title = {Cold-plasma coagulation in the treatment of malignant pleural mesothelioma: results of a combined approach.}, journal = {Interactive cardiovascular and thoracic surgery}, volume = {10}, number = {4}, pages = {502-505}, doi = {10.1510/icvts.2009.223768}, pmid = {20075037}, issn = {1569-9285}, mesh = {Aged ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use ; Chemotherapy, Adjuvant ; Cisplatin/administration & dosage ; Doxorubicin/administration & dosage ; Electrocoagulation/adverse effects/*methods ; Feasibility Studies ; Humans ; *Hyperthermia, Induced/adverse effects ; Male ; Mesothelioma/pathology/*therapy ; Neoplasm Staging ; Pilot Projects ; Pleural Neoplasms/pathology/*therapy ; Quality of Life ; Radiotherapy, Adjuvant ; Retrospective Studies ; *Thoracotomy/adverse effects ; Time Factors ; Treatment Outcome ; }, abstract = {Malignant pleural mesothelioma is on a continuous rise throughout the Western countries. It is associated with asbestos fibre exposition in the past. Surgical approaches include extrapleural pneumonectomy and pleurectomy/decortication (P/D). We investigated the feasability of the implementation of cold-plasma coagulation (CPC) on the pleura, pericardium and diaphragm into an established therapeutic algorithm consisting of P/D and hyperthermic intrathoracal chemoperfusion (HITHOC) therapy. The underlying rationale was the prevention of cardiotoxic effects during HITHOC as well as accidental translocation of malignant cells to the abdomen. CPC was done as part of a multimodal therapy in stage III mesothelioma patients. Histologic examinations of pleural excisates after CPC were done. The patients were followed up in three-month intervals. Neither parenchymal fistulas, nor cardiotoxic effects were observed. The histologic examination of the pleural excisates showed complete predictable necrosis. Moreover, until now (median time after operation 1 year) no relapse of the disease was observed. CPC proved to be a safe technique when used on the pleura, pericardium and diaphragm. We consider our trial as a pilot-study. To evaluate potential survival benefits using this technique larger trials are mandatory.}, } @article {pmid20074451, year = {2009}, author = {Nishimura, Y and Maeda, M and Kumagai, N and Hayashi, H and Miura, Y and Otsuki, T}, title = {Decrease in phosphorylation of ERK following decreased expression of NK cell-activating receptors in human NK cell line exposed to asbestos.}, journal = {International journal of immunopathology and pharmacology}, volume = {22}, number = {4}, pages = {879-888}, doi = {10.1177/039463200902200403}, pmid = {20074451}, issn = {0394-6320}, mesh = {Antigens, CD/drug effects ; Asbestos, Serpentine/*toxicity ; Down-Regulation ; Enzyme Inhibitors/pharmacology ; Flow Cytometry ; Humans ; K562 Cells ; Killer Cells, Natural/*drug effects/enzymology/immunology ; Mitogen-Activated Protein Kinase 1/*metabolism ; Mitogen-Activated Protein Kinase 3/*metabolism ; NK Cell Lectin-Like Receptor Subfamily K/*drug effects/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphoinositide-3 Kinase Inhibitors ; Phosphorylation ; Protein Phosphatase 1/antagonists & inhibitors/metabolism ; Protein Phosphatase 2/antagonists & inhibitors/metabolism ; Receptors, Immunologic/drug effects ; Signal Transduction/drug effects ; Signaling Lymphocytic Activation Molecule Family ; src-Family Kinases/antagonists & inhibitors/metabolism ; }, abstract = {YT-CB5, which had been continuously cultured with chrysotile B (CB)asbestos, showed impaired cytotoxicity with decreased expression of NKG2D and 2B4 NK cell-activating receptors. In the present study, the phosphorylation of extracellular signal-regulated kinase (ERK), which is known to induce degranulation downstream of many NK cell-activating receptors, was examined in YT-CB5 by flow cytometry and compared with the control line YT-Org. YT-CB5 exhibited impaired phosphorylation of ERK1/2 induced by the recognition of K562 cells, downstream of a process mediated by Src family kinase and phosphoinositide 3-kinase. YT-CB5 also exhibited impaired phosphorylation of ERK1/2 following incubation with K562 cells in the presence of anti-2B4 antibodies, where co-stimulation by 2B4 augmented the phosphorylation of ERK1/2 in YT-CB5 to a similar degree as in YT-Org. The phosphorylation of ERK1/2 induced by an inhibitor against phosphatase (PP) 1 and PP2A was also lower in YT-CB5 compared with YT-Org. Moreover, bead-bound antibodies to NKG2D, which contribute to cytotoxicity against K562 cells, induced negligible phosphorylation of ERK1/2 in YT-CB5, although antibodies to 2B4 induced a comparatively greater level of phosphorylation. Additionally, peripheral blood (PB-) NK cells with low expression of NKG2D showed lower phosphorylation of ERK1/2 mediated by anti-NKG2D antibodies compared with PB-NK cells with high expression of NKG2D. These results indicate that signal transduction events leading to the phosphorylation of ERK is impaired in YT-CB5 due to decreased expression of NKG2D. Further studies are required to clarify whether this suppressive effect of asbestos exposure on NK cells might promote lung cancer and mesothelioma in people who have inhaled asbestos.}, } @article {pmid20068227, year = {2010}, author = {Heintz, NH and Janssen-Heininger, YM and Mossman, BT}, title = {Asbestos, lung cancers, and mesotheliomas: from molecular approaches to targeting tumor survival pathways.}, journal = {American journal of respiratory cell and molecular biology}, volume = {42}, number = {2}, pages = {133-139}, pmid = {20068227}, issn = {1535-4989}, mesh = {Animals ; Apoptosis/drug effects ; Asbestos/*toxicity ; ErbB Receptors/metabolism ; Humans ; Lung Neoplasms/*etiology/metabolism ; MAP Kinase Signaling System/drug effects ; Mesothelioma/*etiology/metabolism ; Models, Biological ; NF-kappa B/metabolism ; Oxidants/metabolism ; Proto-Oncogene Mas ; Proto-Oncogene Proteins c-fos/metabolism ; Proto-Oncogene Proteins c-jun/metabolism ; Receptors, Tumor Necrosis Factor/metabolism ; Signal Transduction/drug effects ; Transcription Factor AP-1/metabolism ; }, abstract = {Fifteen years have passed since we published findings in the AJRCMB demonstrating that induction of early response fos/jun proto-oncogenes in rodent tracheal and mesothelial cells correlates with fibrous geometry and pathogenicity of asbestos. Our study was the first to suggest that the aberrant induction of signaling responses by crocidolite asbestos and erionite, a fibrous zeolite mineral associated with the development of malignant mesotheliomas (MMs) in areas of Turkey, led to altered gene expression. New data questioned the widely held belief at that time that the carcinogenic effects of asbestos in the development of lung cancer and MM were due to genotoxic or mutagenic effects. Later studies by our group revealed that proto-oncogene expression and several of the signaling pathways activated by asbestos were redox dependent, explaining why antioxidants and antioxidant enzymes were elevated in lung and pleura after exposure to asbestos and how they alleviated many of the phenotypic and functional effects of asbestos in vitro or after inhalation. Since these original studies, our efforts have expanded to understand the interface between asbestos-induced redox-dependent signal transduction cascades, the relationship between these pathways and cell fate, and the role of asbestos and cell interactions in development of asbestos-associated diseases. Of considerable significance is the fact that the signal transduction pathways activated by asbestos are also important in survival and chemoresistance of MMs and lung cancers. An understanding of the pathogenic features of asbestos fibers and dysregulation of signaling pathways allows strategies for the prevention and therapy of asbestos-related diseases.}, } @article {pmid20068226, year = {2010}, author = {Brody, AR}, title = {Asbestos and lung disease.}, journal = {American journal of respiratory cell and molecular biology}, volume = {42}, number = {2}, pages = {131-132}, doi = {10.1165/rcmb.2010-2002ED}, pmid = {20068226}, issn = {1535-4989}, mesh = {Asbestos/*toxicity ; Asbestosis/etiology ; Humans ; Lung Diseases/*etiology/metabolism ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Oxidants/metabolism ; }, } @article {pmid20065947, year = {2010}, author = {Hu, Q and Akatsuka, S and Yamashita, Y and Ohara, H and Nagai, H and Okazaki, Y and Takahashi, T and Toyokuni, S}, title = {Homozygous deletion of CDKN2A/2B is a hallmark of iron-induced high-grade rat mesothelioma.}, journal = {Laboratory investigation; a journal of technical methods and pathology}, volume = {90}, number = {3}, pages = {360-373}, doi = {10.1038/labinvest.2009.140}, pmid = {20065947}, issn = {1530-0307}, mesh = {Animals ; Comparative Genomic Hybridization ; Cyclin-Dependent Kinase Inhibitor p15/*genetics ; Cyclin-Dependent Kinase Inhibitor p16/*genetics ; Female ; Ferric Compounds/*metabolism/pharmacology ; Ferric Oxide, Saccharated ; *Gene Deletion ; Gene Expression Profiling ; Genes, p16 ; Glucaric Acid ; Hematinics ; Male ; Mesoderm/metabolism ; Mesothelioma/chemically induced/classification/*genetics/metabolism/pathology ; Mucoproteins/metabolism ; Oligonucleotide Array Sequence Analysis ; Oxidative Stress ; Peritoneal Neoplasms/chemically induced/classification/*genetics/metabolism/pathology ; Rats ; Rats, Inbred F344 ; Rats, Wistar ; Transcription Factors ; Uromodulin ; }, abstract = {In humans, mesothelioma has been linked to asbestos exposure, especially crocidolite and amosite asbestos, which contain high amounts of iron. Previously, we established a rat model of iron-induced peritoneal mesothelioma with repeated intraperitoneal injections of iron saccharate and an iron chelator, nitrilotriacetate. Here, we analyze these mesotheliomas using array-based comparative genomic hybridization (aCGH) and gene expression profiling by microarray. Mesotheliomas were classified into two distinct types after pathologic evaluation by immunohistochemistry. The major type, epithelioid mesothelioma (EM), originated in the vicinity of tunica vaginalis testis, expanded into the upper peritoneal cavity and exhibited papillary growth and intense podoplanin immunopositivity. The minor type, sarcomatoid mesothelioma (SM), originated from intraperitoneal organs and exhibited prominent invasiveness and lethality. Both mesothelioma types showed male preponderance. SMs revealed massive genomic alterations after aCGH analysis, including homozygous deletion of CDKN2A/2B and amplification of ERBB2 containing region, whereas EMs showed less genomic alterations. Uromodulin was highly expressed in most of the cases. After 4-week treatment, iron deposition in the mesothelia was observed with 8-hydroxy-2'-deoxyguanosine formation. These results not only show two distinct molecular pathways for iron-induced peritoneal mesothelioma, but also support the hypothesis that oxidative stress by iron overload is a major cause of CDKN2A/2B homozygous deletion.}, } @article {pmid20064790, year = {2010}, author = {Tse, LA and Yu, IT and Goggins, W and Clements, M and Wang, XR and Au, JS and Yu, KS}, title = {Are current or future mesothelioma epidemics in Hong Kong the tragic legacy of uncontrolled use of asbestos in the past?.}, journal = {Environmental health perspectives}, volume = {118}, number = {3}, pages = {382-386}, pmid = {20064790}, issn = {1552-9924}, mesh = {Adult ; Asbestos/*adverse effects ; Female ; Hong Kong/epidemiology ; Humans ; Male ; Mesothelioma/*chemically induced/diagnosis/*epidemiology/etiology ; Middle Aged ; Occupational Exposure/*adverse effects ; Risk Factors ; Time Factors ; }, abstract = {Inhaled asbestos fibers may contribute to three-fourths of malignant mesotheliomas diagnosed in men and almost 40% of cases diagnosed in women. Bans on the manufacture and sale of amphibole asbestos fibers are expected to reduce the incidence of mesothelioma, but the long latency period from initial exposure to clinical disease means that people exposed before bans were enacted will continue to develop asbestos-related mesotheliomas as they age. Tse et al. (p. 382) used historical data on asbestos consumption and mesothelioma diagnoses to predict future mesothelioma trends in Hong Kong. Asbestos use peaked during a construction boom in the early 1960s and subsequently declined by > 90% following a ban on the sale and import of crocidolite and amosite asbestos in 1996, whereas mesothelioma diagnoses in men increased from a single case in 1972–1976 to 63 cases in 2002–2006 (corresponding to crude incidence rates of 0.09 and 3.86 cases/million men, respectively). Assuming an average latency of 42 years, the authors predict that incidence rates will peak in 2009 and that diagnoses will peak in 2014. However, they caution that ongoing use of chrysotile asbestos and the release of asbestos fibers from older buildings during demolition or renovation may slow the projected decline. [corrected]}, } @article {pmid20049974, year = {2010}, author = {Samedi, V and White, S and Zimarowski, MJ and Harris, A and Saffitz, J and Wang, HH}, title = {Metastatic peritoneal mesothelioma in the setting of recurrent ascites: a case report.}, journal = {Diagnostic cytopathology}, volume = {38}, number = {9}, pages = {675-681}, doi = {10.1002/dc.21300}, pmid = {20049974}, issn = {1097-0339}, mesh = {Aged ; Ascites/*complications/*pathology ; Ascitic Fluid/pathology ; Autopsy ; Biopsy ; Fatal Outcome ; Humans ; Immunohistochemistry ; Male ; Mesothelioma/*complications/*pathology/surgery ; Neoplasm Metastasis ; Peritoneal Neoplasms/*complications/*pathology/surgery ; Peritoneum/pathology ; Recurrence ; Skin/pathology ; }, abstract = {Malignant peritoneal mesothelioma is uncommon but rapidly fatal with a median survival of less than 1 year. The diagnosis of this entity is often delayed because of the nonspecific presenting symptoms and nonspecific cytological features of the mesothelial cells in the peritoneal fluids. A 72-year-old man who had no known history of exposure to asbestos and had longstanding refractory ascites thought to be secondary to alcoholic cirrhosis was found to have widespread metastatic malignant mesothelioma involving the lung, liver, pancreas, peritoneal, and pelvic wall, skin and subcutaneous tissue.}, } @article {pmid20049814, year = {2009}, author = {Sanchez, VC and Pietruska, JR and Miselis, NR and Hurt, RH and Kane, AB}, title = {Biopersistence and potential adverse health impacts of fibrous nanomaterials: what have we learned from asbestos?.}, journal = {Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology}, volume = {1}, number = {5}, pages = {511-529}, pmid = {20049814}, issn = {1939-0041}, support = {R01 ES016178/ES/NIEHS NIH HHS/United States ; P42 ES013660-056029/ES/NIEHS NIH HHS/United States ; R01 ES016178-02/ES/NIEHS NIH HHS/United States ; P42 ES013660-010002/ES/NIEHS NIH HHS/United States ; R01 ES03721/ES/NIEHS NIH HHS/United States ; T32 ES007272/ES/NIEHS NIH HHS/United States ; P42 ES013660/ES/NIEHS NIH HHS/United States ; R01 ES003721/ES/NIEHS NIH HHS/United States ; R01 ES003721-20/ES/NIEHS NIH HHS/United States ; R01 ES016178-03/ES/NIEHS NIH HHS/United States ; T32 ES007272-15/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Asbestos/pharmacokinetics/poisoning/toxicity ; Humans ; Lung Diseases/chemically induced/metabolism ; Mice ; Nanostructures/*poisoning/toxicity/ultrastructure ; }, abstract = {Human diseases associated with exposure to asbestos fibers include pleural fibrosis and plaques, pulmonary fibrosis (asbestosis), lung cancer, and diffuse malignant mesothelioma. The critical determinants of fiber bioactivity and toxicity include not only fiber dimensions, but also shape, surface reactivity, crystallinity, chemical composition, and presence of transition metals. Depending on their size and dimensions, inhaled fibers can penetrate the respiratory tract to the distal airways and into the alveolar spaces. Fibers can be cleared by several mechanisms, including the mucociliary escalator, engulfment, and removal by macrophages, or through splitting and chemical modification. Biopersistence of long asbestos fibers can lead to inflammation, granuloma formation, fibrosis, and cancer. Exposure to synthetic carbon nanomaterials, including carbon nanofibers and carbon nanotubes (CNTs), is considered a potential health hazard because of their physical similarities with asbestos fibers. Respiratory exposure to CNTs can produce an inflammatory response, diffuse interstitial fibrosis, and formation of fibrotic granulomas similar to that observed in asbestos-exposed animals and humans. Given the known cytotoxic and carcinogenic properties of asbestos fibers, toxicity of fibrous nanomaterials is a topic of intense study. The mechanisms of nanomaterial toxicity remain to be fully elucidated, but recent evidence suggests points of similarity with asbestos fibers, including a role for generation of reactive oxygen species, oxidative stress, and genotoxicity. Considering the rapid increase in production and use of fibrous nanomaterials, it is imperative to gain a thorough understanding of their biologic activity to avoid the human health catastrophe that has resulted from widespread use of asbestos fibers.}, } @article {pmid20047972, year = {2010}, author = {Rudd, RM}, title = {Malignant mesothelioma.}, journal = {British medical bulletin}, volume = {93}, number = {}, pages = {105-123}, doi = {10.1093/bmb/ldp047}, pmid = {20047972}, issn = {1471-8391}, mesh = {Asbestos/toxicity ; Asbestos, Amphibole/toxicity ; Asbestos, Serpentine/toxicity ; Environmental Exposure ; Humans ; *Mesothelioma/diagnosis/epidemiology/etiology/therapy ; Prognosis ; Risk Assessment ; Risk Factors ; Simian virus 40/pathogenicity ; }, abstract = {INTRODUCTION: Mesothelioma is a malignant tumour of the pleura or peritoneum caused by asbestos. It is increasing in frequency and the prognosis remains grim, with average survival around 1 year.

SOURCES OF DATA: Medical literature and personal experience.

AREAS OF AGREEMENT: Amphibole fibres are far more potent than chrysotile in causing mesothelioma.

AREAS OF CONTROVERSY: A minority view suggests that mesotheliomas in those exposed to chrysotile are caused only by tremolite (an amphibole) which contaminates chrysotile. There is a hypothesis, for which evidence is weakening, that Simian virus 40 may cause mesothelioma.

GROWING POINTS: There is emerging evidence of genetic variation in susceptibility to fibre carcinogenesis. There are developments in treatment, particularly chemotherapy with pemetrexed and cisplatin which prolongs survival and helps symptoms.

Targeted agents for treatment are under investigation and may improve the outlook. The role of radical and palliative surgery requires clarification.}, } @article {pmid20032640, year = {2010}, author = {Bisceglia, M and Dor, DB and Carosi, I and Vairo, M and Pasquinelli, G}, title = {Paratesticular mesothelioma. Report of a case with comprehensive review of literature.}, journal = {Advances in anatomic pathology}, volume = {17}, number = {1}, pages = {53-70}, doi = {10.1097/PAP.0b013e3181c66fbc}, pmid = {20032640}, issn = {1533-4031}, mesh = {Aged ; Humans ; Lymphatic Metastasis ; Male ; Mesothelioma/*pathology ; Neoplasm Recurrence, Local/pathology ; Testicular Neoplasms/*pathology ; }, abstract = {Paratesticular mesotheliomas are rare tumors with 223 cases described so far. The sole plausible causative factor so far ascertained in the pathogenesis of these tumors is asbestos, which however is found in only around 30% to 40% of such cases. The age range of affected individuals is wide, mostly adults and the elderly, but also includes young people and children. The most common presenting symptom is either hydrocele of unknown origin or intrascrotal mass. When hydrocele is the presenting symptom, these tumors are often clinically overlooked and the diagnosis is delayed. Most paratesticular mesotheliomas arise in the tunica vaginalis, but primary tumors of the spermatic cord and epididymis are also on record. Tumors arising from the peritoneal mesothelium of a hernia sac are excluded from this group. The correct diagnosis is almost always made after histologic examination of the operative specimen. Immunohistochemistry and electron microscopy are always helpful and sometimes necessary tools for diagnosis. So far very few cases have been identified or suspected preoperatively on cytologic examination. Three clinicopathologic types of malignant mesotheliomas of the male genital tract are recognized: diffuse tubulo-papillary mesothelioma, well-differentiated papillary mesothelioma, and multicystic mesothelioma. The histologic subtypes are almost always pure epithelial or biphasic. The differential diagnosis is mainly with serous papillary tumors arising from Mullerian vestiges, but several diverse primary or secondary tumors also need to be considered. A clinicopathologic evaluation of a case of tunical diffuse mesothelioma in a 74-year-old male from the AMR Series is the starting point for this general review.}, } @article {pmid20021458, year = {2009}, author = {Tomasetti, M and Amati, M and Santarelli, L and Alleva, R and Neuzil, J}, title = {Malignant mesothelioma: biology, diagnosis and therapeutic approaches.}, journal = {Current molecular pharmacology}, volume = {2}, number = {2}, pages = {190-206}, doi = {10.2174/1874467210902020190}, pmid = {20021458}, issn = {1874-4702}, mesh = {Asbestos/toxicity ; Carcinogens/toxicity ; DNA Damage ; Humans ; Mesothelioma/*diagnosis/metabolism/therapy ; Mitogen-Activated Protein Kinases/metabolism ; NF-kappa B/metabolism ; Simian virus 40/physiology ; Transcription Factor AP-1/metabolism ; }, abstract = {Malignant mesothelioma (MM) is an aggressive neoplasm of serosal cavities, which is resistant to conventional therapy, with patient survival from presentation of <12 months. MM remains a universally fatal disease of increasing incidence worldwide. Although the main risk factor is asbestos exposure, other factors, Simian virus 40 infection and inheritance of susceptibility genes, likely play a role. Asbestos-related carcinogenic process is primarily based on the interaction between susceptibility (genetic and acquired) and exposure to carcinogenic environmental agents. Asbestos-induced carcinogenesis includes generation of reactive oxygen species, which induce DNA strand breaks and oxidant-induced base modifications to DNA. Persistent oxidative DNA damage can alter signaling cascades, gene expression, induce or arrest transcription, and increase replication errors and genomic instability. The long promotion phase observed in MM pathogenesis and the absence of early symptoms both contribute to late diagnosis of the disease. This results in delayed therapeutic intervention of patients, making the outcome of the disease very grim. There have been several developments in MM management, principally based on early detection, improved diagnosis, development of more effective therapies, and new insights into the pathobiology of the disease. Several programs have been used to screen asbestos-exposed individuals for lung and pleural disease. These programs involve annual pulmonary function tests, chest radiography and high resolution computer tomography. Blood tests make screening of target populations an attractive strategy. Many current gene and protein expression studies aim to identify clinically useful biomarkers and new therapeutic targets for improved management of MM.}, } @article {pmid20017186, year = {2010}, author = {Aguilar-Madrid, G and Robles-Pérez, E and Juárez-Pérez, CA and Alvarado-Cabrero, I and Rico-Méndez, FG and Javier, KG}, title = {Case-control study of pleural mesothelioma in workers with social security in Mexico.}, journal = {American journal of industrial medicine}, volume = {53}, number = {3}, pages = {241-251}, doi = {10.1002/ajim.20780}, pmid = {20017186}, issn = {1097-0274}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Case-Control Studies ; Female ; Humans ; Incidence ; Insurance Coverage ; Logistic Models ; Male ; Mesothelioma/*epidemiology/pathology ; Mexico/epidemiology ; Middle Aged ; Occupational Diseases/*epidemiology/pathology ; Occupational Exposure/*adverse effects/classification ; Odds Ratio ; Pleural Neoplasms/*epidemiology/pathology ; Risk Factors ; Social Security ; Socioeconomic Factors ; Surveys and Questionnaires ; Time Factors ; }, abstract = {BACKGROUND: Environmental and occupational exposure to asbestos in Mexico in the past has been a cause of deaths and health damages. Its magnitude is unknown to date. Our objective was to identify the proportion of cases of malignant pleural mesothelioma (MPM) that can be attributed to and occupational exposure to asbestos.

METHODS: We carried out a case-control study of MPM in 472 workers insured by the Mexican Institute of Social Security, all Valley of Mexico residents, with 119 incident cases and 353 controls. Cases were histologically confirmed. Participants were questioned concerning their occupational history and sociodemographic data. Assignment to one of the four exposures was performed qualitatively by an expert hygienist. Odds ratios (ORs) and attributable risks (ARs) were calculated using a non-conditional logistic regression model.

RESULTS: A total of 80.6% of cases and 31.5% of controls had occupational exposure to asbestos. ORs were adjusted for age and gender and by exposure category, and exhibited an increase with probability of exposure as follows: 3.7(95% CI 1.3-10.4) for the likely category and 14.3(95% CI 8-26) for the certain category; AR in the group occupationally exposed to asbestos was 83.2%, and the population AR was 44%.

CONCLUSIONS: Our results show that the relationship between industrial uses of all forms of asbestos is generating an increase in mesothelioma-related diseases and deaths among Mexican workers. As a public health policy, Mexico should prohibit the use of asbestos in all production processes with the aim of controlling the epidemic and preventing the occurrence of new cases of MPM.}, } @article {pmid20007574, year = {2009}, author = {Currie, AJ and Prosser, A and McDonnell, A and Cleaver, AL and Robinson, BW and Freeman, GJ and van der Most, RG}, title = {Dual control of antitumor CD8 T cells through the programmed death-1/programmed death-ligand 1 pathway and immunosuppressive CD4 T cells: regulation and counterregulation.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {183}, number = {12}, pages = {7898-7908}, doi = {10.4049/jimmunol.0901060}, pmid = {20007574}, issn = {1550-6606}, mesh = {Animals ; Antigens, Surface/*physiology ; Apoptosis Regulatory Proteins/*physiology ; B7-1 Antigen/*physiology ; B7-H1 Antigen ; CD8-Positive T-Lymphocytes/*immunology/metabolism/*pathology ; Cell Line, Tumor ; Contraindications ; Female ; Lymph Nodes/immunology/metabolism/pathology ; Lymphocyte Activation/immunology ; Lymphocyte Depletion ; Membrane Glycoproteins/antagonists & inhibitors/*physiology ; Mesothelioma/*immunology/pathology/therapy ; Mice ; Mice, Inbred BALB C ; Mice, Transgenic ; Peptides/antagonists & inhibitors/*physiology ; Programmed Cell Death 1 Receptor ; Signal Transduction/*immunology ; Stromal Cells/immunology/metabolism/pathology ; T-Lymphocytes, Regulatory/*immunology/metabolism/*pathology ; }, abstract = {Tumors have evolved multiple mechanisms to evade immune destruction. One of these is expression of T cell inhibitory ligands such as programmed death-ligand 1 (PD-L1; B7-H1). In this study, we show that PD-L1 is highly expressed on mesothelioma tumor cells and within the tumor stroma. However, PD-L1 blockade only marginally affected tumor growth and was associated with the emergence of activated programmed death-1(+) ICOS(+) CD4 T cells in tumor-draining lymph nodes, whereas few activated CD8 T cells were present. Full activation of antitumor CD8 T cells, characterized as programmed death-1(+) ICOS(+) Ki-67(+) and displaying CTL activity, was only observed when CD4 T cells were depleted, suggesting that a population of suppressive CD4 T cells exists. ICOS(+) foxp3(+) regulatory T cells were found to be regulated through PD-L1, identifying one potentially suppressive CD4 T cell population. Thus, PD-L1 blockade activates antitumor CD8 T cell most potently in the absence of CD4 T cells. These findings have implications for the development of PD-L1-based therapies.}, } @article {pmid20000675, year = {2010}, author = {Ishida, T and Alexandrov, M and Nishimura, T and Minakawa, K and Hirota, R and Sekiguchi, K and Kohyama, N and Kuroda, A}, title = {Selective detection of airborne asbestos fibers using protein-based fluorescent probes.}, journal = {Environmental science & technology}, volume = {44}, number = {2}, pages = {755-759}, doi = {10.1021/es902395h}, pmid = {20000675}, issn = {0013-936X}, mesh = {Air Pollutants/*chemistry ; Asbestos/*chemistry ; Carcinogens/*chemistry ; Escherichia coli Proteins/*chemistry ; Fluorescent Dyes/*chemistry ; Microscopy, Fluorescence/*methods ; Sensitivity and Specificity ; }, abstract = {Fluorescence microscopy (FM) is one of the most important analytical tools in modern life sciences, sufficiently sensitive to allow observation of single molecules. Here we describe the first application of the FM technique for the detection of inorganic environmental pollutants-airborne asbestos fibers that can cause asbestosis, mesothelioma, and lung cancer. In order to assess FM capabilities for detecting and counting asbestos fibers, we screened E. coli lysate for proteins that bind to amphibole asbestos. In combination with the previously discovered E. coli protein DksA (Kuroda et al., Biotechnol. Bioeng. 2008, 99, 285-289) that can specifically bind to chrysotile, the newly identified GatZ protein was used for selective and highly sensitive detection of two different asbestos types. Our novel FM-based method overcomes a number of limitations of the commonly used phase-contrast microscopy (PCM) method, offering a convenient alternative to PCM for airborne asbestos monitoring.}, } @article {pmid19999568, year = {2009}, author = {Hasegawa, S}, title = {[Therapeutic strategies for resectable malignant pleural mesothelioma].}, journal = {Nihon Geka Gakkai zasshi}, volume = {110}, number = {6}, pages = {338-342}, pmid = {19999568}, issn = {0301-4894}, mesh = {Clinical Trials as Topic ; Humans ; Mesothelioma/*therapy ; Pleural Neoplasms/*therapy ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare thoracic malignancy associated with very poor prognosis. Because no single treatment is very effective for MPM, a combination of preoperative chemotherapy, extrapleural pneumonectomy, and postoperative hemithoracic radiation is currently considered the "standard" therapy for resectable MPM. As such an aggressive protocol involves very high risk, maximum preoperative assessment for durability and curability is required. Very recently, the results of three major clinical trials of trimodality treatment for MPM have been reported from North America and Europe. The therapeutic regimens and results of these trials were similar. Although the overall results were not encouraging, surprisingly good survival rates were noted in patients who had no mediastinal node involvement and completed the entire trimodality therapy regimen. This clearly illustrates that patient selection plays a key role in MPM treatment. Two other important clinical trials are currently ongoing. The Mesothelioma and Radical Surgery (MARS) trial is a randomized clinical trial seeking to clarify the role of radical surgery in MPM treatment. An all-Japan clinical study of trimodality treatment for MPM is currently underway as a part of a national campaign entitled "Comprehensive Strategy against Asbestos-Related Diseases."}, } @article {pmid19999565, year = {2009}, author = {Kurumatani, N and Tomioka, K}, title = {[Epidemiology of pleural mesothelioma in Japan].}, journal = {Nihon Geka Gakkai zasshi}, volume = {110}, number = {6}, pages = {320-325}, pmid = {19999565}, issn = {0301-4894}, mesh = {Aged ; Environmental Exposure ; Female ; Humans ; Japan/epidemiology ; Male ; Mesothelioma/*mortality ; Occupational Exposure ; Pleural Neoplasms/*mortality ; }, abstract = {We describe the trend in pleural mesothelioma mortality rates since 1995, when the International Statistical Classification of Disease and Related Health Problems came into effect in Japan, and outline the risk factors for the disease. The number of pleural mesothelioma cases has been increasing in both genders, although male deaths predominated over female ones every year. In 2007, the latest year for which data are available, 652 deaths occurred among men and 130 among women, which was only one-fifth of that among men. The annual death rates were 0.88 and 0.20 per 10(5), respectively. The distribution of 5-year age-specific deaths was skewed toward younger age, with a single peak at 70-74 years in men but at 75-79 years in women. Birth cohort analysis showed that age-specific death rates from the disease became higher with younger birth year in men. Asbestos exposure causes pleural mesothelioma. Some cohort studies clarified the high mortality rate from the disease, which was reported to reach 0.5 x 10(3)/year among those with occupational asbestos exposure. Depending on the amount and variety of asbestos used in industrial plants, the range at which neighborhood asbestos exposure can increase the risk of residents developing pleural mesothelioma can be as much as 2,000 meters from an emission point.}, } @article {pmid19999328, year = {2009}, author = {Marrannes, J and Delvaux, S and Verheezen, J}, title = {Malignant peritoneal mesothelioma: contribution and limitation of imaging for its diagnosis.}, journal = {JBR-BTR : organe de la Societe royale belge de radiologie (SRBR) = orgaan van de Koninklijke Belgische Vereniging voor Radiologie (KBVR)}, volume = {92}, number = {5}, pages = {248-250}, pmid = {19999328}, issn = {1780-2393}, mesh = {Aged ; Anorexia ; Antineoplastic Agents/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage ; Biomarkers, Tumor/metabolism ; Biopsy ; Cisplatin/administration & dosage ; Contrast Media ; Diagnosis, Differential ; Fatal Outcome ; Female ; Glutamates/administration & dosage ; Guanine/administration & dosage/analogs & derivatives ; Humans ; Immunohistochemistry ; Mesothelioma/*diagnostic imaging/drug therapy/metabolism ; Pemetrexed ; Peritoneal Neoplasms/*diagnostic imaging/drug therapy/metabolism ; Peritoneum/diagnostic imaging ; Radiographic Image Enhancement/methods ; Rare Diseases ; Tomography, X-Ray Computed ; Weight Loss ; }, abstract = {Malignant mesothelioma of the peritoneum is a rare primary peritoneal tumor with a pore prognosis. The overall prevalence is one to two cases per million. The tumor arises from mesothelial cells in the pleura or, in this case, peritoneum. Peritoneal malignant mesotheliomas account for only 10 to 20% of all malignant mesotheliomas. Exposure to asbestos fibers is a known risk factor for the development of mesothelial tumors. Although imaging features can be suggestive of malignant peritoneal mesothelioma, histologic examination of tissue with specific immunohistologic markers are mandatory for diagnosis.}, } @article {pmid19960781, year = {2009}, author = {Giacomini, S and Mensi, C and Sieno, C and Riboldi, L}, title = {[Asbestos-related malignant mesothelioma of the pleura in a young person].}, journal = {La Medicina del lavoro}, volume = {100}, number = {5}, pages = {396}, pmid = {19960781}, issn = {0025-7818}, mesh = {Adult ; Age Factors ; Asbestos/*adverse effects ; *Carcinogens ; Humans ; Male ; Mesothelioma/diagnosis/*etiology ; Occupational Diseases/diagnosis/*etiology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/diagnosis/*etiology ; Surveys and Questionnaires ; Time Factors ; }, } @article {pmid19960346, year = {2010}, author = {Wang, Y and Rishi, AK and Puliyappadamba, VT and Sharma, S and Yang, H and Tarca, A and Dou, QP and Lonardo, F and Ruckdeschel, JC and Pass, HI and Wali, A}, title = {Targeted proteasome inhibition by Velcade induces apoptosis in human mesothelioma and breast cancer cell lines.}, journal = {Cancer chemotherapy and pharmacology}, volume = {66}, number = {3}, pages = {455-466}, pmid = {19960346}, issn = {1432-0843}, support = {P30 CA022453/CA/NCI NIH HHS/United States ; }, mesh = {Antineoplastic Combined Chemotherapy Protocols/administration & dosage/*pharmacology ; Apoptosis/*drug effects ; Blotting, Western ; Boronic Acids/administration & dosage ; Bortezomib ; Breast Neoplasms/*drug therapy/pathology ; Cell Cycle/drug effects ; Cell Line, Tumor ; Cisplatin/administration & dosage ; Dose-Response Relationship, Drug ; Drug Delivery Systems ; Drug Synergism ; Female ; Flow Cytometry ; Humans ; Mesothelioma/*drug therapy/pathology ; Pilot Projects ; Protease Inhibitors/administration & dosage/*pharmacology ; Proteasome Inhibitors ; Pyrazines/administration & dosage ; Signal Transduction/drug effects ; Time Factors ; }, abstract = {INTRODUCTION: Thoracic malignancies and human breast cancer (HBC) continue to be aggressive solid tumors that are poor responders to the existing conventional standard chemotherapeutic approaches. Malignant pleural mesothelioma (MPM) is an asbestos-related tumor of the thoracic pleura that lacks effective treatment options. Altered ubiquitin proteasome pathway is frequently encountered in many malignancies including HBC and MPM and thus serves as an important target for therapeutic intervention strategies. Although proteasome inhibitor Velcade (Bortezomib) has been under clinical investigation for a number of cancers, limited preclinical studies with this agent have thus far been conducted in HBC and MPM malignancies.

PURPOSE: To study the biological and molecular responses of MPM and HBC cells to Velcade treatments, and to identify mechanisms involved in transducing growth inhibitory effects of this agent.

METHODS: Flow-cytometric analyses coupled with western immunoblotting and gene-array methodologies were utilized to determine mechanisms of Velcade-dependent growth suppression of five MPM (H2595, H2373, H2452, H2461, and H2714) and two breast cancer (MDA MB-468, SKBR-3) cell lines.

RESULTS: Our data revealed significant reduction in cell growth properties that were dose and time dependent. Velcade treatment resulted in G2M phase arrest, increased expression of cyclin-dependent kinase inhibitor p21 and pro-apoptotic protein Bax. Pretreatment of mesothelioma cells with Velcade showed synergistic effect with cisplatin combination regimens. High-throughput gene expression profiling among Velcade treated and untreated mesothelioma cell lines resulted in identification of novel transducers of apoptosis such as CARP-1, XAF1, and Troy proteins.

CONCLUSIONS: Velcade targets cell cycle and apoptosis signaling to suppress MPM and HBC growth in part by activating novel transducers of apoptosis. This pilot study has paved way for further in-depth analysis of the downstream target molecules associated with presensitization of mesothelioma cells in finding effective therapeutic treatment options for both mesothelioma and recalcitrant breast cancers.}, } @article {pmid19937944, year = {2010}, author = {Rekhi, B and Pathuthara, S and Ajit, D and Kane, SV}, title = {"Signet-ring" cells--a caveat in the diagnosis of a diffuse peritoneal mesothelioma occurring in a lady presenting with recurrent ascites: an unusual case report.}, journal = {Diagnostic cytopathology}, volume = {38}, number = {6}, pages = {435-439}, doi = {10.1002/dc.21248}, pmid = {19937944}, issn = {1097-0339}, mesh = {Adenocarcinoma/pathology ; Ascites/*etiology/pathology ; Ascitic Fluid/pathology ; Carcinoma, Signet Ring Cell/complications/*pathology ; Cytodiagnosis ; *Diagnostic Errors ; Female ; Humans ; Immunohistochemistry ; Mesothelioma/complications/*pathology ; Middle Aged ; Peritoneal Neoplasms/complications/*pathology ; }, abstract = {A diffuse peritoneal mesothelioma is a rare tumor. Exfoliative cytology forms the first step in the diagnosis of mesothelioma, since most of these cases presented with effusion. Despite well established cytomorphological features, a challenge exists in differentiating mesothelial cells, including reactive and malignant types from carcinoma cells and macrophages. Presence of "signet-ring" cells increases the diagnostic challenge as these can be forms of benign and malignant cells. Ancillary techniques like immunohistochemical (IHC) markers and ultrastructural analysis form useful adjunct in substantiating exact diagnosis. We report an unusual case study of a diffuse peritoneal mesothelioma in a 57-years-old lady, with no history of asbestos exposure, presenting with recurrent ascites, diagnosed on ascitic fluid cytology and on histology as an adenocarcinoma, based upon the presence of "signet-ring" cells. On review, clinicopathological correlation with IHC was helpful in forming correct diagnosis.}, } @article {pmid19935710, year = {2010}, author = {Watanabe, Y and Kojima, T and Kagawa, S and Uno, F and Hashimoto, Y and Kyo, S and Mizuguchi, H and Tanaka, N and Kawamura, H and Ichimaru, D and Urata, Y and Fujiwara, T}, title = {A novel translational approach for human malignant pleural mesothelioma: heparanase-assisted dual virotherapy.}, journal = {Oncogene}, volume = {29}, number = {8}, pages = {1145-1154}, doi = {10.1038/onc.2009.415}, pmid = {19935710}, issn = {1476-5594}, mesh = {Adenoviridae/enzymology/*genetics/growth & development ; Animals ; Cell Line, Tumor ; Combined Modality Therapy ; Gene Expression Regulation, Neoplastic ; Gene Transfer Techniques ; *Genetic Therapy ; Glucuronidase/*genetics/metabolism ; Humans ; Lung Neoplasms/chemically induced/therapy ; Mesothelioma/chemically induced/*therapy ; Mice ; Mice, Nude ; Neoplasm Transplantation ; *Oncolytic Virotherapy ; Pleural Neoplasms/pathology/*therapy ; Protein Biosynthesis ; Transfection/*methods ; Virus Replication ; Xenograft Model Antitumor Assays ; }, abstract = {Malignant pleural mesothelioma (MPM) is a highly aggressive tumor that is related to asbestos exposure. MPM is characterized by rapid and diffuse local growth in the thoracic cavity, and it has a poor prognosis because it is often refractory to conventional therapy. Although MPM is an extraordinarily challenging disease to treat, locoregional virotherapy may be useful against this aggressive disease because of the accessibility by intrapleural virus delivery. In this study, we show that telomerase-specific, replication-selective adenovirus OBP-301 can efficiently infect and kill human mesothelioma cells by viral replication. Intrathoracic administration of virus significantly reduced the number and size of human mesothelioma tumors intrathoracically implanted into nu/nu mice. A high-definition, fluorescence optical imaging system with an ultra-thin, flexible fibered microprobe clearly detected intracellular replication of green fluorescent protein-expressing oncolytic virus in intrathoracically established mesothelioma tumors. As the extracellular matrix (ECM) may contribute to the physiological resistance of a solid tumor by preventing the penetration of therapeutic agents (including oncolytic viruses), we also examined whether the co-expression of heparanase, an endoglucuronidase capable of specifically degrading heparan sulfate, that influences the physiological barrier to macromolecule penetration, can modify the permeability of the ECM, resulting in profound therapeutic efficacy. Co-injection of OBP-301 and a replication-defective adenovirus (Ad-S/hep)-expressing heparanase resulted in more profound antitumor effects without apparent toxicity in an orthotopic pleural dissemination model. Our results suggest that intrathoracic dual virotherapy with telomerase-specific oncolytic adenovirus in combination with heparanase-expressing adenovirus may be efficacious in the prevention and treatment of pleural dissemination of human malignant mesothelioma.}, } @article {pmid19934120, year = {2009}, author = {Mensi, C and Garberi, A and Trinco, R and Riboldi, L}, title = {The upholsterer and the asbestos.}, journal = {Occupational and environmental medicine}, volume = {66}, number = {12}, pages = {855}, doi = {10.1136/oem.2009.050658}, pmid = {19934120}, issn = {1470-7926}, mesh = {Asbestos/*toxicity ; Humans ; Interior Design and Furnishings ; Italy ; Male ; Mesothelioma/*etiology ; Middle Aged ; Occupational Diseases/*etiology ; Occupational Exposure/adverse effects ; Pleural Neoplasms/*etiology ; Registries ; }, } @article {pmid19925375, year = {2009}, author = {Pukkala, E and Martinsen, JI and Lynge, E and Gunnarsdottir, HK and Sparén, P and Tryggvadottir, L and Weiderpass, E and Kjaerheim, K}, title = {Occupation and cancer - follow-up of 15 million people in five Nordic countries.}, journal = {Acta oncologica (Stockholm, Sweden)}, volume = {48}, number = {5}, pages = {646-790}, doi = {10.1080/02841860902913546}, pmid = {19925375}, issn = {1651-226X}, mesh = {Adolescent ; Adult ; Female ; Follow-Up Studies ; Humans ; Incidence ; Male ; Middle Aged ; Neoplasms/*epidemiology/etiology ; Occupational Diseases/*epidemiology/etiology ; Occupational Exposure/*adverse effects ; Occupations ; Prognosis ; Scandinavian and Nordic Countries/epidemiology ; Young Adult ; }, abstract = {We present up to 45 years of cancer incidence data by occupational category for the Nordic populations. The study covers the 15 million people aged 30-64 years in the 1960, 1970, 1980/1981 and/or 1990 censuses in Denmark, Finland, Iceland, Norway and Sweden, and the 2.8 million incident cancer cases diagnosed in these people in a follow-up until about 2005. The study was undertaken as a cohort study with linkage of individual records based on the personal identity codes used in all the Nordic countries. In the censuses, information on occupation for each person was provided through free text in self-administered questionnaires. The data were centrally coded and computerised in the statistical offices. For the present study, the original occupational codes were reclassified into 53 occupational categories and one group of economically inactive persons. All Nordic countries have a nation-wide registration of incident cancer cases during the entire study period. For the present study the incident cancer cases were classified into 49 primary diagnostic categories. Some categories have been further divided according to sub-site or morphological type. The observed number of cancer cases in each group of persons defined by country, sex, age, period and occupation was compared with the expected number calculated from the stratum specific person years and the incidence rates for the national population. The result was presented as a standardised incidence ratio, SIR, defined as the observed number of cases divided by the expected number. For all cancers combined (excluding non-melanoma skin cancer), the study showed a wide variation among men from an SIR of 0.79 (95% confidence interval 0.66-0.95) in domestic assistants to 1.48 (1.43-1.54) in waiters. The occupations with the highest SIRs also included workers producing beverage and tobacco, seamen and chimney sweeps. Among women, the SIRs varied from 0.58 (0.37-0.87) in seafarers to 1.27 (1.19-1.35) in tobacco workers. Low SIRs were found for farmers, gardeners and teachers. Our study was able to repeat most of the confirmed associations between occupations and cancers. It is known that almost all mesotheliomas are associated with asbestos exposure. Accordingly, plumbers, seamen and mechanics were the occupations with the highest risk in the present study. Mesothelioma was the cancer type showing the largest relative differences between the occupations. Outdoor workers such as fishermen, gardeners and farmers had the highest risk of lip cancer, while the lowest risk was found among indoor workers such as physicians and artistic workers. Studies of nasal cancer have shown increased risks associated with exposure to wood dust, both for those in furniture making and for those exposed exclusively to soft wood like the majority of Nordic woodworkers. We observed an SIR of 1.84 (1.66-2.04) in male and 1.88 (0.90-3.46) in female woodworkers. For nasal adenocarcinoma, the SIR in males was as high as 5.50 (4.60-6.56). Male waiters and tobacco workers had the highest risk of lung cancer, probably attributable to active and passive smoking. Miners and quarry workers also had a high risk, which might be related to their exposure to silica dust and radon daughters. Among women, tobacco workers and engine operators had a more than fourfold risk as compared with the lung cancer risk among farmers, gardeners and teachers. The occupational risk patterns were quite similar in all main histological subtypes of lung cancer. Bladder cancer is considered as one of the cancer types most likely to be related to occupational carcinogens. Waiters had the highest risk of bladder cancer in men and tobacco workers in women, and the low-risk categories were the same ones as for lung cancer. All this can be accounted for by smoking. The second-highest SIRs were among chimney sweeps and hairdressers. Chimney sweeps are exposed to carcinogens such as polycyclic aromatic hydrocarbons from the chimney soot, and hairdressers' work environment is also rich in chemical agents. Exposure to the known hepatocarcinogens, the Hepatitis B virus and aflatoxin, is rare in the Nordic countries, and a large proportion of primary liver cancers can therefore be attributed to alcohol consumption. The highest risks of liver cancer were seen in occupational categories with easy access to alcohol at the work place or with cultural traditions of high alcohol consumption, such as waiters, cooks, beverage workers, journalists and seamen. The risk of colon cancer has been related to sedentary work. The findings in the present study did not strongly indicate any protective role of physical activity. Colon cancer was one of the cancer types showing the smallest relative variation in incidence between occupational categories. The occupational variation in the risk of female breast cancer (the most common cancer type in the present series, 373 361 cases) was larger, and there was a tendency of physically demanding occupations to show SIRs below unity. Women in occupations which require a high level of education have, on average, a higher age at first child-birth and elevated breast cancer incidence. Women in occupational categories with the highest average number of children had markedly lower incidence. In male breast cancer (2 336 cases), which is not affected by the dominating reproductive factors, there was a suggestion of an increase in risk in occupations characterised by shift work. Night-shift work was recently classified as probably carcinogenic, with human evidence based on breast cancer research. The most common cancer among men in the present cohort was prostate cancer (339 973 cases). Despite the huge number of cases, we were unable to demonstrate any occupation-related risks. The observed small occupational variation could be easily explained by varying PSA test frequency. The Nordic countries are known for equity and free and equal access to health care for all citizens. The present study shows that the risk of cancer, even under these circumstances, is highly dependent on the person's position in the society. Direct occupational hazards seem to explain only a small percentage of the observed variation - but still a large number of cases - while indirect factors such as life style changes related to longer education and decreasing physical activity become more important. This publication is the first one from the extensive Nordic Occupational Cancer (NOCCA) project. Subsequent studies will focus on associations between specific work-related factors and cancer diseases with the aim to identify exposure-response patterns. In addition to the cancer data demonstrated in the present publication, the NOCCA project produced Nordic Job Exposure Matrix (described in separate articles in this issue of Acta Oncologica) that transforms information about occupational title histories to quantitative estimates of specific exposures. The third essential component is methodological development related to analysis and interpretation of results based on averaged information of exposures and co-factors in the occupational categories.}, } @article {pmid19921706, year = {2010}, author = {Strand, LA and Martinsen, JI and Koefoed, VF and Sommerfelt-Pettersen, J and Grimsrud, TK}, title = {Asbestos-related cancers among 28,300 military servicemen in the Royal Norwegian Navy.}, journal = {American journal of industrial medicine}, volume = {53}, number = {1}, pages = {64-71}, doi = {10.1002/ajim.20778}, pmid = {19921706}, issn = {1097-0274}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Asbestosis/*epidemiology ; Cohort Studies ; Colorectal Neoplasms/epidemiology ; Cross-Sectional Studies ; Humans ; Incidence ; Laryngeal Neoplasms/epidemiology ; Lung Neoplasms/pathology ; Male ; Mesothelioma/epidemiology ; Middle Aged ; Military Personnel/*statistics & numerical data ; Naval Medicine/*statistics & numerical data ; Neoplasms/*epidemiology ; Norway ; Pharyngeal Neoplasms/epidemiology ; Pleural Neoplasms/epidemiology ; Risk Factors ; Stomach Neoplasms/epidemiology ; Young Adult ; }, abstract = {INTRODUCTION: This study focus on the incidence of asbestos-related cancers among 28,300 officers and enlisted servicemen in the Royal Norwegian Navy. Until 1987, asbestos aboard the vessels potentially caused exposure to 11,500 crew members.

METHODS: Standardized incidence ratios (SIR) were calculated for malignant mesothelioma, lung cancer, and laryngeal, pharyngeal, stomach, and colorectal cancers according to service aboard between 1950 and 1987 and in other Navy personnel.

RESULTS: Increased risk of mesothelioma was seen among engine room crews, with SIRs of 6.23 (95% CI = 2.51-12.8) and 6.49 (95% CI = 2.11-15.1) for personnel who served less than 2 years and those with longer service, respectively. Lung cancer was nearly 20% higher than expected among both engine crews and non-engine crews. An excess of colorectal cancer bordering on statistical significance was seen among non-engine crews (SIR = 1.14; 95% CI = 0.98-1.32). Land-based personnel and personnel who served aboard after 1987 had lower lung cancer incidence than expected (SIR = 0.77; 95% CI = 0.64-0.92). No elevated risk of laryngeal, pharyngeal, or stomach cancers was seen.

CONCLUSION: The overall increase (65%) in mesotheliomas among military Navy servicemen was confined to marine engine crews only. The mesothelioma incidence can be taken as an indicator of the presence or absence of asbestos exposure, but it offered no consistent explanation to the variation in incidence of other asbestos-related cancers.}, } @article {pmid19909234, year = {2009}, author = {Pasello, G and Favaretto, A}, title = {Molecular targets in malignant pleural mesothelioma treatment.}, journal = {Current drug targets}, volume = {10}, number = {12}, pages = {1235-1244}, doi = {10.2174/138945009789753200}, pmid = {19909234}, issn = {1873-5592}, mesh = {Angiogenesis Inhibitors/therapeutic use ; Animals ; Antineoplastic Agents/*therapeutic use ; Cell Cycle Proteins/drug effects/physiology ; Hepatocyte Growth Factor/physiology ; Histone Deacetylase Inhibitors/therapeutic use ; Humans ; Insulin-Like Growth Factor Binding Protein 1/antagonists & inhibitors ; Intercellular Signaling Peptides and Proteins/physiology ; Mesothelioma/*drug therapy ; Platelet-Derived Growth Factor/antagonists & inhibitors ; Pleural Neoplasms/*drug therapy ; Proteasome Endopeptidase Complex/drug effects ; Proto-Oncogene Proteins c-met/physiology ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; }, abstract = {Malignant mesothelioma is an aggressive tumour of the serosal surfaces with poor prognosis and increasing incidence due to widespread previous asbestos exposure. Relative chemotherapeutic and radiotherapeutic resistance makes malignant pleural mesothelioma (MPM) difficult to manage, even though encouraging results were achieved with multimodality treatment. Better knowledge of angiogenesis and molecular pathways involved in MPM seems to be the right way to define new targets for systemic treatment. Neoangiogenesis may be considered as a critical step in the development of mesothelioma. Vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) are autocrine growth factors in MPM and epidermal growth factor receptor (EGFR) appears highly expressed in this tumour. Tyrosine kinase inhibitors (TKIs) targeting growth factors like vandetanib, dasatinib, and angiogenesis inhibitors like bevacizumab, are among the most promising agents under evaluation in clinical trials. Mesothelioma is a malignancy which owes its chemoresistance to an apoptotic defect. Thus the introduction of new biologic drugs like vorinostat, bortezomib, everolimus and temsirolimus, in the treatment of MPM finds a strong rationale. This review focuses on the current target therapies and evaluates future biologic approaches for the systemic management of MPM.}, } @article {pmid19883435, year = {2009}, author = {Kurimoto, R and Kishimoto, T and Nagai, Y and Takazawa, H and Sakaue, N and Shinohara, Y and Hiroshima, K}, title = {Malignant peritoneal mesothelioma: quantitative analysis of asbestos burden.}, journal = {Pathology international}, volume = {59}, number = {11}, pages = {823-827}, doi = {10.1111/j.1440-1827.2009.02452.x}, pmid = {19883435}, issn = {1440-1827}, mesh = {Aged ; Asbestos/*adverse effects/*analysis ; Asbestosis/*pathology ; Body Burden ; Humans ; Male ; Mesothelioma/*etiology/pathology ; Mineral Fibers/adverse effects/analysis ; Peritoneal Neoplasms/*etiology/pathology ; }, abstract = {Malignant mesotheliomas develop commonly in the pleural cavity and rarely arise in the peritoneal cavity. It is well established that asbestos exposure is related to malignant pleural mesothelioma, but the asbestos burden in the abdominal cavity in patients with malignant peritoneal mesothelioma has not been well studied. The purpose of the present study was therefore to report on an autopsy case of malignant peritoneal mesothelioma with quantitative analysis of the asbestos burden in tissues from the pleura and organs in the abdominal cavity. The patient was a 67-year-old man with a history of asbestos exposure. The peritoneum was thickened with diffuse tumor proliferation. This patient was diagnosed as having malignant peritoneal epithelioid mesothelioma. The number of asbestos fibers was >10,000/g dry tissue in all samples examined except in the small intestine. The number of asbestos fibers in the stomach was 53,000/g, which was higher than that in a control asbestosis subject. The existence of numerous asbestos fibers found in the abdominal cavity suggests that asbestos stimuli are related to the tumorigenesis of malignant peritoneal mesothelioma.}, } @article {pmid19880210, year = {2010}, author = {Torii, I and Hashimoto, M and Terada, T and Kondo, N and Fushimi, H and Shimazu, K and Takeda, S and Takuwa, T and Okumura, Y and Sato, A and Yamamoto, T and Fukuoka, K and Tanaka, F and Nishigami, T and Nakano, T and Hasegawa, S and Tsujimura, T}, title = {Well-differentiated papillary mesothelioma with invasion to the chest wall.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {67}, number = {2}, pages = {244-247}, doi = {10.1016/j.lungcan.2009.10.004}, pmid = {19880210}, issn = {1872-8332}, mesh = {Female ; Humans ; Immunohistochemistry ; Incidental Findings ; Mesothelioma/metabolism/*pathology/surgery ; Middle Aged ; Mucin-1/metabolism ; Pleural Effusion, Malignant/pathology ; Pleural Neoplasms/metabolism/*pathology/surgery ; Pneumonectomy ; Thoracic Wall/*pathology ; }, abstract = {Well-differentiated papillary mesothelioma (WDPM) is an uncommon tumor with a papillary architecture, bland cytologic features, a tendency toward superficial spread without invasion, and good prognosis with prolonged survival. WDPM occurs primarily in the peritoneum of women, but also rarely in the pleura. We here report a case of 48-year-old woman who developed WDPM in the pleura with no history of asbestos exposure. Tumors were multifocal and widespread with a velvety appearance on the surface of parietal and visceral pleurae resected by extrapleural pneumonectomy (EPP). Tumors showed papillary structures with fibrovascular cores and lined by epithelioid cells. Immunohistochemically, these epithelioid tumor cells were positive for epithelial membrane antigen (EMA), a marker of malignant mesothelioma, with more than 50% positive for p53. Tumor cells microinvaded into subpleural parenchyma of the lung and minimally spread to adipose tissues of the mediastinal lesion. In addition, tumor cells invaded into the chest wall with a trabecular or glandular architecture. Based on these findings, this case is pathologically considered as WDPM of the pleura with malignant potential.}, } @article {pmid19875971, year = {2009}, author = {Yildirim, H and Metintas, M and Entok, E and Ak, G and Ak, I and Dundar, E and Erginel, S}, title = {Clinical value of fluorodeoxyglucose-positron emission tomography/computed tomography in differentiation of malignant mesothelioma from asbestos-related benign pleural disease: an observational pilot study.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {4}, number = {12}, pages = {1480-1484}, doi = {10.1097/JTO.0b013e3181c0a7ff}, pmid = {19875971}, issn = {1556-1380}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Carcinogens/pharmacology ; Diagnosis, Differential ; Female ; *Fluorodeoxyglucose F18 ; Humans ; Male ; Mesothelioma/*diagnostic imaging ; Middle Aged ; Pilot Projects ; Pleural Diseases/*diagnostic imaging/etiology ; Pleural Neoplasms/*diagnostic imaging ; Positron-Emission Tomography/*methods ; Prognosis ; *Radiopharmaceuticals ; Tomography, X-Ray Computed ; }, abstract = {BACKGROUND: Several studies have already addressed the potential role of an increased fluorine 18 fluorodeoxyglucose (18F FDG) uptake in identification of pleural malignancy. In this pilot study, we investigate the role of 18F-FDG positron emission tomography/computed tomography (PET/CT) for differentiating asbestos-related benign pleural disease from malignant mesothelioma.

MATERIALS AND METHODS: The study population comprised 31 consecutive patients (17 malignant mesotheliomas, nine benign asbestos pleurisies, and five diffuse pleural fibrosis) with a mean age of 61 years between January 2006 and December 2008. Thoracoscopy or image-guided pleural needle biopsy were systematically performed to reveal pathologic diagnosis and/or clinical follow-up for at least 3 years for presence or absence of malignant pleural effusion. ROCs analyses for standardized uptake value (SUV) adjusted to body weight were calculated between benign and malignant pleural diseases.

RESULTS: 18F-FDG PET/CT imaging correctly detected the presence of malignancies in 15 of 17 patients with malignant mesothelioma for sensitivity, specificity, and overall accuracy of 88.2%, 92.9%, and 90.3%, respectively. 18F-FDG PET/CT imaging correctly identified 13 of 14 cases of benign pleural disease. The mean SUV values were 6.5 +/- 3.4 for malignant mesothelioma cases and 0.8 +/- 0.6 for benign pleural diseases (p < 0.001). When we compared the two groups of pleural disease, a cut-off value of 2.2 for SUV gave the best accuracy with 94.1%, 100%, 100%, and 93.3% for sensitivity, specificity, positive predictive value, and negative predictive value, respectively.

CONCLUSION: Preliminary results of this trial provide evidence that 18F-FDG PET/CT imaging is a highly accurate and reliable noninvasive test to decide for further investigation of differentiating malignant mesothelioma from benign pleural disease.}, } @article {pmid19865072, year = {2010}, author = {Driece, HA and Siesling, S and Swuste, PH and Burdorf, A}, title = {Assessment of cancer risks due to environmental exposure to asbestos.}, journal = {Journal of exposure science & environmental epidemiology}, volume = {20}, number = {5}, pages = {478-485}, doi = {10.1038/jes.2009.56}, pmid = {19865072}, issn = {1559-064X}, mesh = {Asbestos/*adverse effects ; Asbestos, Crocidolite/isolation & purification ; Asbestos, Serpentine/isolation & purification ; Environment Design ; Environmental Exposure/*adverse effects ; Environmental Monitoring/*methods ; Epidemiological Monitoring ; Humans ; Industry ; Mesothelioma/*chemically induced/epidemiology ; Netherlands/epidemiology ; Residence Characteristics/statistics & numerical data ; Risk Assessment ; Rural Health ; Soil Pollutants/analysis ; Waste Products/*adverse effects ; }, abstract = {In a rural area widespread pollution of friable and non-friable waste products was present, used to harden dirt tracks, yards, and driveways during 1935-1974. Exposure to environmental asbestos was assessed by a site approach, based on number of polluted sites within postal code areas, and by a household approach, based on number of households in the close vicinity to polluted sites within postal code areas. Based on asbestos soil investigations, 293 sites were identified with asbestos waste material at the surface, of which 77% contained crocidolite fibres as well as chrysotile fibres. The 293 sites-at-risk varied from 5 m(2) to 2722 m(2) and were surrounded by 347 households within 100 m of these sites. Distance to the plant was associated with the number of sites (r=0.36), and with the number of households (r=0.52). However, categorization of postal code areas into low, intermediate or high likelihood of exposure to asbestos showed a modest agreement between the site and household approach. In the site approach a total of 2.3 million person-years at risk were estimated with an average exposure of 1674 fibres/m(3) and an expected 1.8 cases of malignant mesothelioma each year. The household approach resulted in estimates of 1.2 million person-years at risk, and 0.9 cases of malignant mesothelioma per year, respectively. This study illustrates that asbestos waste on the surface of roads and yards in an area with over 130,000 inhabitants may result in long-term exposure to asbestos that will cause several cases of malignant mesothelioma each year. Although distance to plant, number of polluted sites and number of exposed household were associated, the modest agreement among these measures of exposure indicate that the exposure assessment strategy chosen in a particular study may result in considerable misclassification. Without detailed information on individual behaviour within the polluted area, it is difficult to show that a more individually oriented approach will perform better than an ecological approach.}, } @article {pmid19864204, year = {2009}, author = {Tsou, MT and Luo, JC}, title = {Porcelain factory worker with asbestos-related mesothelioma.}, journal = {Journal of the Formosan Medical Association = Taiwan yi zhi}, volume = {108}, number = {10}, pages = {819-825}, doi = {10.1016/S0929-6646(09)60411-3}, pmid = {19864204}, issn = {0929-6646}, mesh = {Asbestos/*adverse effects ; Humans ; Male ; Manufactured Materials ; Mesothelioma/*diagnostic imaging/etiology ; Middle Aged ; Occupational Exposure/adverse effects ; Pleural Neoplasms/*diagnostic imaging/etiology ; Taiwan ; Tomography, X-Ray Computed/adverse effects ; }, abstract = {Malignant mesothelioma is a rare tumor among the general population, but for people exposed to asbestos, the lifetime risk is high. A 58-year old man presented with suffering from chest pain, upper back pain, shortness of breath, and coughing that had continued for several months. A chest X-ray revealed right-side pleural effusion; however, pleural biopsy from drainage treatment confirmed a diagnosis of malignant mesothelioma. According to his occupational and environmental history, the patient had worked continuously in a porcelain factory for 30 years. The specific characteristics of his work, making asbestos wallboards and gaskets, entailed working in high-temperature conditions with a high fine-particle content in the atmosphere. The high working temperature caused asbestos debris and dust to fall down regularly from the wallboards, however, it was not until recently that the patient had started to wear personal protection. Asbestos is a significant source of hazardous exposure in old buildings, and this case serves as a reminder of the importance of asbestos-related exposure history, which facilitated the correct diagnosis of pulmonary malignant mesothelioma. Asbestos-containing materials that are now banned or regulated are still present in older buildings and remain an exposure hazard; they continue to be a serious health concern in many countries.}, } @article {pmid19858537, year = {2010}, author = {Cristaudo, A and Foddis, R and Bonotti, A and Simonini, S and Vivaldi, A and Guglielmi, G and Bruno, R and Landi, D and Gemignani, F and Landi, S}, title = {Polymorphisms in the putative micro-RNA-binding sites of mesothelin gene are associated with serum levels of mesothelin-related protein.}, journal = {Occupational and environmental medicine}, volume = {67}, number = {4}, pages = {233-236}, doi = {10.1136/oem.2009.049205}, pmid = {19858537}, issn = {1470-7926}, mesh = {Asbestos/toxicity ; Asbestosis/*blood ; Biomarkers, Tumor/blood ; GPI-Linked Proteins ; Humans ; Male ; Membrane Glycoproteins/blood/*genetics ; Mesothelin ; Mesothelioma/blood ; MicroRNAs/genetics ; Middle Aged ; Occupational Diseases/blood ; Occupational Exposure/adverse effects ; Pleural Neoplasms/blood ; Polymorphism, Single Nucleotide/*genetics ; Prognosis ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Serum mesothelin, also known as soluble mesothelin-related protein (SMRP), reportedly shows increased levels in epithelial-type malignant pleural mesothelioma, but sometimes also arrives at high values in healthy asbestos-exposed subjects.

OBJECTIVES: This study aimed to investigate whether single nucleotide polymorphisms in the 3'untranslated region (3'UTR) of the mesothelin-encoded gene (MSLN) are associated with the SMRP levels measured in serum.

METHODS: The 3'UTR of the mesothelin gene was genotyped in 59 healthy asbestos-exposed subjects, selected on the basis of their SMRP levels. Direct sequencing did not show any new polymorphism, but enabled us to genotype two known SNPs (rs1057147, rs57272256). Differences in the mean values of SMRP in wild-type and variant heterozygote groups were calculated.

RESULTS: High levels of SMRP in healthy asbestos-exposed subjects were significantly associated with polymorphism rs1057147 (G
METHODS: TUSC2 insufficiency in clinical specimens of MPM was assessed via RT-PCR (mRNA level), Representational Oligonucleotide Microarray Analysis (DNA level), and immunohistochemical evaluation (protein level). A possible link between TUSC2 expression and exposure to asbestos was studied using asbestos-treated mesothelial cells and ROS (reactive oxygen species) scavengers. Transcripional effects of TUSC2 in MPM were assessed through expression array analysis of TUSC2-transfected MPM cells.

RESULTS: Expression of TUSC2 was downregulated in approximately 84% of MM specimens while loss of TUSC2-containing 3p21.3 region observed in approximately 36% of MPMs including stage 1 tumors. Exposure to asbestos led to a transcriptional suppression of TUSC2, which we found to be ROS-dependent. Expression array studies showed that TUSC2 activates transcription of multiple genes with tumor suppressor properties and down-regulates pro-tumorigenic genes, thus supporting its role as a tumor suppressor. In agreement with our knockout model, TUSC2 up-regulated IL-15 and also modulated more than 40 other genes (approximately 20% of total TUSC2-affected genes) associated with immune system. Among these genes, we identified CD24 and CD274, key immunoreceptors that regulate immunogenic T and B cells and play important roles in systemic autoimmune diseases. Finally, clinical significance of TUSC2 transcriptional effects was validated on the expression array data produced previously on clinical specimens of MPM. In this analysis, 42 TUSC2 targets proved to be concordantly modulated in MM serving as disease discriminators.

CONCLUSION: Our data support immuno-therapeutic potential of TUSC2, define its targets, and underscore its importance as a transcriptional stimulator of anti-tumorigenic pathways.}, } @article {pmid19851532, year = {2009}, author = {Payne, JI and Pichora, E}, title = {Filing for workers' compensation among Ontario cases of mesothelioma.}, journal = {Canadian respiratory journal}, volume = {16}, number = {5}, pages = {148-152}, pmid = {19851532}, issn = {1916-7245}, mesh = {Age Distribution ; Aged ; Female ; Humans ; Incidence ; Male ; Mesothelioma/economics/*epidemiology ; Middle Aged ; Occupational Diseases/economics/*epidemiology ; Ontario/epidemiology ; Registries/*statistics & numerical data ; Sex Distribution ; Workers' Compensation/economics/*statistics & numerical data ; }, abstract = {BACKGROUND/OBJECTIVE: For many types of cancer, disease attribution to occupational exposures is difficult. Mesothelioma, however, is a 'sentinel' occupational cancer associated with asbestos exposure. The present study linked workers' compensation claims data with cancer registry data to explore the completeness of reporting of mesothelioma to the Ontario Workplace Safety and Insurance Board (WSIB) according to characteristics of cases diagnosed among Ontario residents.

METHODS: Two data sources were linked at the person level: the WSIB Occupational Disease Information and Surveillance System and the Ontario Cancer Registry. Filing rates were calculated as the proportion of Ontario Cancer Registry mesothelioma cases (International Classification of Diseases - Oncology code 905) that linked to a WSIB-filed cancer claim. Filing rates were calculated for the period 1980 to 2002, and trends were calculated by year, age and county of residence at diagnosis.

RESULTS: The filing rate for compensation has increased little over the past 20 years, reaching a high of 43% in 2000. Overall, filing rates were highest among pleural mesothelioma cases among men (range 27% to 57%). Filing rates were highest among individuals 50 to 59 years of age and declined substantially throughout the retirement years. There was substantial variation in filing rates by area of residence, with the highest rate being in Lambton County, Ontario.

CONCLUSION: The filing rate for compensation in Ontario was much lower than the estimated proportion of cases eligible for compensation. The increased filing rate in Lambton County was likely related to this community's awareness of the association between asbestos and mesothelioma. Physicians can play an important role in educating patients of their potential entitlement to compensation benefits.}, } @article {pmid19832887, year = {2010}, author = {Moore, S and Darlison, L and Tod, AM}, title = {Living with mesothelioma. A literature review.}, journal = {European journal of cancer care}, volume = {19}, number = {4}, pages = {458-468}, doi = {10.1111/j.1365-2354.2009.01162.x}, pmid = {19832887}, issn = {1365-2354}, mesh = {Caregivers/*psychology ; Delivery of Health Care/methods/standards ; Family/*psychology ; Humans ; Lung Neoplasms/*psychology ; Mesothelioma/*psychology ; Quality of Life/*psychology ; }, abstract = {Mesothelioma is an asbestos-related cancer that affects mainly the pleura. World-wide incidence is increasing and set to rise for some time particularly in developing countries. Mesothelioma is uniformly fatal and often associated with difficult symptoms. The purpose of this review is to identify what is known about the experience of people living with mesothelioma. A literature search identified 13 papers covering qualitative studies, patient-reported quality of life data collected as part of a clinical trial, symptoms and survey of patients and carers. The findings suggest the impact of mesothelioma is multidimensional on: physical symptoms (especially pain, breathlessness, fatigue, cough, sleep disturbance, appetite loss and sweating), emotional functioning (anxiety, depression, fear and isolation), social consequences (changes in roles and relationships) and interventions (the necessity of frequent anti-cancer treatments and admissions for symptom control). The impact on family members is significant also. Although limited, these findings provide an important insight into the impact of mesothelioma on patients and family members and suggest areas where service provision may fail to meet their needs. Finally, the review highlights an urgent need for further research to more fully understand the experience of living with mesothelioma and identify the specific needs of patients and family members.}, } @article {pmid19829978, year = {2009}, author = {James, CO and Woods, AW and Arya, P and Abuelgasim, KA and Heath, LT and Sitapati, A}, title = {Mesothelioma in an HIV/AIDS patient without history of asbestos exposure: possible role for immunosuppression in mesothelioma: a case report.}, journal = {Cases journal}, volume = {2}, number = {}, pages = {7498}, pmid = {19829978}, issn = {1757-1626}, abstract = {We describe a 41-year-old African-American male who initially presented in respiratory distress. He had a positive history of asthma, cigarette smoking, and only recent possible asbestos exposure six months prior to onset of symptoms. Mesothelioma was suspected after chest radiography and PET-CT, and confirmed by immunohistochemical tissue analysis. We postulate that immunosuppression enhances susceptibility to mesothelioma, since weakened immune systems are present in both HIV/AIDS patients like this 41-year-old man, and elderly patients who compose the population that classically presents with mesothelioma. Furthermore, immunosuppression may be a prerequisite to the development of mesothelioma.}, } @article {pmid19827900, year = {2009}, author = {Lee, KH and Yoon, HS and Choi, SJ and Kang, D}, title = {Asbestos exposure and malignant mesothelioma in Korea.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {10}, number = {4}, pages = {707-710}, pmid = {19827900}, issn = {2476-762X}, mesh = {Asbestos/*adverse effects ; Humans ; Incidence ; Korea/epidemiology ; Mesothelioma/*etiology/mortality ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*etiology/mortality ; Survival Rate ; }, abstract = {Although importation of asbestos to Korea has decreased, there are growing concerns of its hazardous effects. This paper describes the use and occupational exposure to asbestos, and the incidence and mortality of malignant mesotheliomas in Korea. Asbestos raw material imports from other countries peaked between 1990 and 1995, but importation of asbestos-containing and -processed materials has steadily increased until now. A comprehensive exposure survey was conducted in Korea between 1995 and 2006. The average airborne asbestos concentration was lower than from other countries and steadily decreased during the study period. The number of malignant mesothelioma cases in Korea was 48 in 1998, 39 in 1999, 45 in 2000, 38 in 2001, and 46 in 2002. There were 334 deaths due to malignant mesothelioma and an average of 30.4 deaths per year between 1996 and 2006. The number of deaths attributed to malignant mesothelioma ranged from 16 cases in 1999 to 57 cases in 2006. The magnitude of asbestos-related health problems in Korea has been underestimated due to under-diagnosis, incomplete reports, and shorter duration of exposure. A nationwide surveillance system for asbestos exposure and malignant mesothelioma should therefore be implemented.}, } @article {pmid19822280, year = {2009}, author = {Pass, HI and Carbone, M}, title = {Current status of screening for malignant pleural mesothelioma.}, journal = {Seminars in thoracic and cardiovascular surgery}, volume = {21}, number = {2}, pages = {97-104}, doi = {10.1053/j.semtcvs.2009.06.007}, pmid = {19822280}, issn = {1043-0679}, mesh = {Asbestos/adverse effects ; Biomarkers, Tumor/*blood ; GPI-Linked Proteins ; Humans ; Mass Screening/*methods ; Membrane Glycoproteins/blood ; Mesothelin ; Mesothelioma/blood/*diagnosis/diagnostic imaging/etiology ; Occupational Exposure ; Osteopontin/blood ; Patient Selection ; Pleural Neoplasms/blood/*diagnosis/diagnostic imaging/etiology ; Predictive Value of Tests ; Risk Assessment ; Risk Factors ; *Tomography, X-Ray Computed ; }, abstract = {Malignant mesothelioma is characterized by its association with asbestos, its long latency period, and the propensity for the diagnosis to be obtained in the later stages of the disease. Because the high-risk cohorts for mesothelioma are fairly well defined by the association with asbestos, and the exposure is usually in the workplace, it is hypothesized that early detection of the disease could (1) find patients at an earlier, more treatable stage and (2) result in prolonged survival over the present median 12 months from the start of therapy. Many studies have used standard chest X-ray to characterize changes associated with asbestos-exposed individuals, but the insensitivity of X-ray in screening patients with mesothelioma has never supported the wide-scale adaptation of such an effort. With the advent of computerized tomography, prospective trials, many of which are chiefly prevalence detection studies, have been performed and stress the importance for proper detailing by carefully qualifying suspicious changes, as well as defining the correct cohort to screen. Most recently, serum biomarkers with the potential to discriminate asbestos-exposed, non-cancer-bearing individuals from those with mesothelioma have been investigated both at single institutions and with multi-institutional-blinded trials. These markers, including soluble mesothelin-related protein, osteopontin, and megakaryocyte potentiating factor, may, in the future, be incorporated into a screening algorithm for high-risk asbestos-exposed individuals to help monitor these cohorts in a noninvasive fashion and guide the use of computerized tomography.}, } @article {pmid19822075, year = {2009}, author = {Nishimura, Y and Miura, Y and Maeda, M and Kumagai, N and Murakami, S and Hayashi, H and Fukuoka, K and Nakano, T and Otsuki, T}, title = {Impairment in cytotoxicity and expression of NK cell- activating receptors on human NK cells following exposure to asbestos fibers.}, journal = {International journal of immunopathology and pharmacology}, volume = {22}, number = {3}, pages = {579-590}, doi = {10.1177/039463200902200304}, pmid = {19822075}, issn = {0394-6320}, mesh = {Antigens, CD/metabolism ; Asbestos, Serpentine/*toxicity ; Case-Control Studies ; Cell Degranulation/drug effects ; Cell Survival/drug effects ; Cytotoxicity, Immunologic/*drug effects ; Dose-Response Relationship, Drug ; Down-Regulation ; Granzymes/metabolism ; Humans ; K562 Cells ; Killer Cells, Natural/*drug effects/immunology/metabolism ; Leukocytes, Mononuclear/drug effects/immunology ; Mesothelioma/*immunology ; NK Cell Lectin-Like Receptor Subfamily K/metabolism ; Natural Cytotoxicity Triggering Receptor 1/metabolism ; Perforin/metabolism ; Receptors, Immunologic/metabolism ; Signaling Lymphocytic Activation Molecule Family ; Time Factors ; }, abstract = {Asbestos is well-known for its tumorigenic activity, but its effect on anti-tumor immunity remains unclear. Therefore, we prepared a sub-line of YT-A1 human NK cells exposed to chrysotile B (CB) asbestos (YT-CB5) as an in vitro model to analyze the effect of asbestos exposure on NK cells, and examined cytotoxicity and expressions of its related molecules. The cytotoxicity of YT-CB5 against K562 cells decreased compared with the original line of YT-A1 (YT-Org). YT-CB5 exhibited significant decreases in expressions of cell surface NKG2D, 2B4 and intracellular granzyme A. YT-CB5 also exhibited a decrease in the 2B4-dependent cytotoxicity. In addition, the degranulations stimulated via cell surface NKG2D and 2B4 also decreased in YT-CB5. Therefore, peripheral blood NK cells in patients with malignant mesothelioma (MM) were examined and compared with healthy volunteers. NK cells in patients with MM also showed decreases in cytotoxicity against K562. Although the expressions of NKG2D and 2B4 did not decrease in NK cells of MM patients, the expression of cell surface NKp46 decreased. To confirm the effect of asbestos exposure on peripheral blood NK cells, PBMCs were cultured under exposure to CB. NK cells in PBMCs exposed to CB in vitro showed a significant decrease in the expression of NKp46, whereas NK cells and alter the expression of NK cell-activating receptors including NKG2D, 2B4 and NKp46 and intracellular perforin/granzymes.cells in PBMCs exposed to glass wool did not show such a decrease. These results indicate that exposure to asbestos has the potential to impair the cytotoxicity of NK cells and alter the expression of NK cell-activating receptors including NKG2D, 2B4 and NKp46 and intracellular perforin/granzymes.}, } @article {pmid19815709, year = {2009}, author = {Shukla, A and Bosenberg, MW and MacPherson, MB and Butnor, KJ and Heintz, NH and Pass, HI and Carbone, M and Testa, JR and Mossman, BT}, title = {Activated cAMP response element binding protein is overexpressed in human mesotheliomas and inhibits apoptosis.}, journal = {The American journal of pathology}, volume = {175}, number = {5}, pages = {2197-2206}, pmid = {19815709}, issn = {1525-2191}, support = {P01 CA114047/CA/NCI NIH HHS/United States ; P30 CA006927/CA/NCI NIH HHS/United States ; P30 CA022435/CA/NCI NIH HHS/United States ; P30CA22435/CA/NCI NIH HHS/United States ; }, mesh = {Antibiotics, Antineoplastic/pharmacology ; Apoptosis/drug effects/*physiology ; Asbestos/pharmacology ; Carcinogens/pharmacology ; Cell Movement/physiology ; Cells, Cultured ; Cyclic AMP Response Element-Binding Protein/genetics/*metabolism ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Doxorubicin/pharmacology ; Epithelium/anatomy & histology/drug effects ; ErbB Receptors/metabolism ; Humans ; Mesothelioma/*metabolism/pathology ; Microarray Analysis ; RNA, Small Interfering/genetics/metabolism ; Signal Transduction/physiology ; }, abstract = {Little is known about the cellular mechanisms contributing to the development and chemoresistance of malignant mesothelioma (MM), an aggressive asbestos-associated tumor. A human mesothelial cell line (LP9/TERT-1) and isolated human pleural mesothelial cells showed rapid and protracted asbestos-induced cAMP response element binding protein (CREB1) phosphorylation, which was inhibited in LP9/TERT-1 cells by small molecule inhibitors of epidermal growth factor receptor phosphorylation and protein kinase A. Asbestos increased expression of several CREB target genes (c-FOS, EGR-1, MKP1, BCL2, and MMP13) and apoptosis, which was enhanced using small interfering CREB. Human MM tissue arrays showed elevated endogenous levels of phosphorylated nuclear CREB1 as compared with reactive mesothelial hyperplasias and normal lung tissue. Significantly increased phosphorylated CREB1 and mRNA levels of BCL2, c-FOS, MMP9, and MMP13 were also observed in MM cells in vitro, which were further augmented after addition of Doxorubicin (Dox). Small interfering CREB inhibited migration of MMs, increased apoptosis by Dox, and decreased BCL2 and BCL-xL expression, suggesting a role for these molecules in CREB-induced MM survival. These data indicate that CREB1 and its target genes are up-regulated in asbestos-exposed human mesothelial cells through an epidermal growth factor receptor/protein kinase A pathway. Since activated CREB1 also is increased endogenously in human MM and modifies migration and resistance to Dox-induced apoptosis, inhibition of CREB1 may be a new strategy for MM therapy.}, } @article {pmid19804678, year = {2009}, author = {Cree, M and Lalji, M and Jiang, B and Carriere, KC and Beach, J and Kamruzzaman, A}, title = {Explaining Alberta's rising mesothelioma rates.}, journal = {Chronic diseases in Canada}, volume = {29}, number = {4}, pages = {144-152}, pmid = {19804678}, issn = {1481-8523}, mesh = {Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Alberta/epidemiology ; Asbestos/adverse effects ; Cohort Effect ; Cohort Studies ; Female ; Humans ; Incidence ; Linear Models ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Pleural Neoplasms/*epidemiology/etiology ; Registries ; Sex Distribution ; }, abstract = {Although mesothelioma rates have been rising worldwide, little is known about mesothelioma trends in Alberta. This population-based descriptive study used Alberta Cancer Board Registry data from 1980 to 2004 to develop an age-period-cohort model of male pleural mesothelioma incidence rates over time. Both age and cohort effects are associated with incidence rates. The highest-risk cohort comprised men born between 1930 and 1939, reflecting widespread asbestos use and exposure beginning in the 1940s in Canada. We predict that 1393 Albertan men 40 years and older will die of pleural mesothelioma between 1980 and 2024; 783 (56.2%) of these deaths will occur between 2010 and 2024. The total number of mesothelioma deaths in Alberta will be higher when all age groups, both sexes, and all disease sites are included, with numbers likely peaking sometime between 2015 and 2019. In addition to the ongoing efforts that focus on eliminating asbestos-related disease in Alberta, the challenge is to implement surveillance systems to prevent future epidemics of preventable occupational cancers in Alberta.}, } @article {pmid19793348, year = {2010}, author = {Sekido, Y}, title = {Genomic abnormalities and signal transduction dysregulation in malignant mesothelioma cells.}, journal = {Cancer science}, volume = {101}, number = {1}, pages = {1-6}, pmid = {19793348}, issn = {1349-7006}, mesh = {Asbestos/toxicity ; Cyclin-Dependent Kinase Inhibitor p16/genetics ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; MAP Kinase Signaling System ; Mesothelioma/*genetics/metabolism/therapy ; *Mutation ; Neurofibromatosis 2/genetics ; Phosphatidylinositol 3-Kinases/physiology ; Proto-Oncogene Proteins c-akt/physiology ; Signal Transduction/*physiology ; Tumor Suppressor Protein p14ARF/genetics ; }, abstract = {Malignant mesothelioma (MM) is a tumor with poor prognosis associated with asbestos exposure. While it remains to be clarified how asbestos fibers confer genetic/epigenetic alterations and induce cellular transformation in normal mesothelial cells, the understanding of key molecular mechanisms of MM cell development, proliferation, and invasion has progressed. MM shows frequent genetic inactivation of tumor suppressor genes of p16(INK4a)/p14(ARF) and neurofibromatosis type 2 (NF2) which encodes Merlin, and epigenetic inactivation of RASSF1A. However, no frequent mutations of well-known oncogenes such as K-RAS and PIK3CA have been identified. Activation of multiple receptor tyrosine kinases including the epidermal growth factor receptor (EGFR) family and MET, and subsequent deregulations of mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase (PI3K)-AKT signaling cascades are frequently observed in most MM cells. The tumor suppressive function of Merlin in MM cells is also being investigated by dissecting its possible downstream signaling cascade called the Hippo pathway. Further comprehensive delineation of dysregulated signaling cascades in MM cells will lead to identification of key addiction pathways for cell survival and proliferation of MM cells, which strongly promote establishment of a new molecular target therapy for MM.}, } @article {pmid19783208, year = {2010}, author = {Pesch, B and Taeger, D and Johnen, G and Gross, IM and Weber, DG and Gube, M and Müller-Lux, A and Heinze, E and Wiethege, T and Neumann, V and Tannapfel, A and Raithel, HJ and Brüning, T and Kraus, T}, title = {Cancer mortality in a surveillance cohort of German males formerly exposed to asbestos.}, journal = {International journal of hygiene and environmental health}, volume = {213}, number = {1}, pages = {44-51}, doi = {10.1016/j.ijheh.2009.09.001}, pmid = {19783208}, issn = {1618-131X}, mesh = {Aged ; Asbestos/*adverse effects ; Asbestosis/complications/*mortality ; Cause of Death ; Environmental Exposure ; Fibrosis/complications/etiology ; Germany/epidemiology ; Humans ; Inhalation Exposure ; Lung Neoplasms/etiology/*mortality ; Male ; Mesothelioma/etiology/*mortality ; Middle Aged ; *Occupational Exposure ; Pleural Neoplasms/etiology/*mortality ; Regression Analysis ; Risk Assessment ; }, abstract = {The objective of this analysis was the estimation of the cancer risks of asbestos and asbestosis in a surveillance cohort of high-exposed German workers. A group of 576 asbestos workers was selected for high-resolution computer tomography of the chest in 1993-1997. A mortality follow-up was conducted through 2007. Standardised mortality ratios (SMRs) were calculated and Poisson regression was performed to assess mesothelioma risks. A high risk was observed for pleural mesothelioma (SMR 28.10, 95% CI 15.73-46.36) that decreased after cessation of exposure (RR 0.1; 95% CI 0.0-0.6 for > or =30 vs. <30 years after last exposure). Asbestosis was a significant risk factor for mesothelioma (RR 6.0, 95% CI 2.4-14.7). Mesothelioma mortality was still in excess in former asbestos workers although decreasing after cessation of exposure. Fibrosis was associated with subsequent malignancy.}, } @article {pmid19764192, year = {2009}, author = {Bianchi, C and Bianchi, T}, title = {[Malignant mesothelioma of the pleura among Finance Police personnel].}, journal = {La Medicina del lavoro}, volume = {100}, number = {4}, pages = {313}, pmid = {19764192}, issn = {0025-7818}, mesh = {Asbestos/adverse effects/analysis ; Commerce ; Humans ; Hyalin ; Italy ; Mesothelioma/chemistry/*epidemiology/pathology ; Military Personnel/*statistics & numerical data ; Occupational Diseases/*epidemiology/pathology ; Occupational Exposure ; Pleural Neoplasms/chemistry/*epidemiology/pathology ; Smoking/adverse effects ; Transportation ; }, } @article {pmid19764072, year = {2009}, author = {Scarselli, A and Scano, P and Marinaccio, A and Iavicoli, S}, title = {Occupational cancer in Italy: evaluating the extent of compensated cases in the period 1994-2006.}, journal = {American journal of industrial medicine}, volume = {52}, number = {11}, pages = {859-867}, doi = {10.1002/ajim.20758}, pmid = {19764072}, issn = {1097-0274}, mesh = {Asbestos/adverse effects ; Humans ; Italy/epidemiology ; Lung Neoplasms/epidemiology ; Multivariate Analysis ; Neoplasms/economics/*epidemiology ; Nose Neoplasms/epidemiology ; Occupational Diseases/economics/*epidemiology ; Pleural Neoplasms/epidemiology ; Urinary Bladder Neoplasms/epidemiology ; Workers' Compensation/*statistics & numerical data ; Workplace ; }, abstract = {OBJECTIVE: The aim of this study is to analyze occupational cancer claims compensated in the industrial sector in Italy between 1994 and 2006.

METHODS: A descriptive analysis of compensated occupational cancers based on the Italian Workers' Compensation Authority (INAIL) data was performed. Summary statistics were compiled by sex and age of worker, cancer type, workplace agent and economic sector. The temporal trend in the period 1994-2006 was investigated for the most frequently compensated cancers (mesothelioma and lung cancer from asbestos; nasal cavities cancer from wood and leather dust).

RESULTS: Between 1994 and 2006, 6,243 cancer claims were compensated by INAIL due to occupational exposure in the industrial sector. Most (5,288, or 85%) of these compensated claims occurred in the period 2000-2006, when the annual mean of the most compensated cancers increased approximately four times compared to the period 1994-1999.

CONCLUSIONS: There is an increasing trend in compensation for work-related cancers in Italy in recent years, even if occupational cancers are still widely underreported.}, } @article {pmid19757446, year = {2009}, author = {Silverstein, MA and Welch, LS and Lemen, R}, title = {Developments in asbestos cancer risk assessment.}, journal = {American journal of industrial medicine}, volume = {52}, number = {11}, pages = {850-858}, doi = {10.1002/ajim.20756}, pmid = {19757446}, issn = {1097-0274}, mesh = {Asbestos/*adverse effects ; Asbestos, Crocidolite/adverse effects ; Humans ; Lung Neoplasms/*epidemiology ; Mesothelioma/*epidemiology ; Models, Statistical ; Occupational Diseases/*epidemiology ; Occupational Exposure ; Pleural Neoplasms/*epidemiology ; Risk Assessment ; Workplace ; }, abstract = {BACKGROUND: Efforts have been made for 25 years to develop asbestos risk assessments that provide valid information about workplace and community cancer risks. Mathematical models have been applied to a group of workplace epidemiology studies to describe the relationships between exposure and risk. EPA's most recent proposed method was presented at a public meeting in July 2008.

METHODS: Risk assessments prepared by USEPA, OSHA, and NIOSH since 1972 were reviewed, along with related literature.

RESULTS AND CONCLUSIONS: None of the efforts to use statistical models to characterize relative cancer potencies for asbestos fiber types and sizes have been able to overcome limitations of the exposure data. Resulting uncertainties have been so great that these estimates should not be used to drive occupational and environmental health policy. The EPA has now rejected and discontinued work on its proposed methods for estimating potency factors. Future efforts will require new methods and more precise and reliable exposure assessments. However, while there may be genuine need for such work, a more pressing priority with regard to the six regulated forms of asbestos and other asbestiform fibers is to ban their production and use.}, } @article {pmid19751749, year = {2009}, author = {Gemignani, F and Neri, M and Bottari, F and Barale, R and Canessa, PA and Canzian, F and Ceppi, M and Spitaleri, I and Cipollini, M and Ivaldi, GP and Mencoboni, M and Scaruffi, P and Tonini, GP and Ugolini, D and Mutti, L and Bonassi, S and Landi, S}, title = {Risk of malignant pleural mesothelioma and polymorphisms in genes involved in the genome stability and xenobiotics metabolism.}, journal = {Mutation research}, volume = {671}, number = {1-2}, pages = {76-83}, doi = {10.1016/j.mrfmmm.2009.09.003}, pmid = {19751749}, issn = {0027-5107}, support = {R03 CA115062/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Case-Control Studies ; Female ; Genetic Association Studies ; *Genomic Instability ; Humans ; Male ; Mesothelioma/*enzymology/*genetics ; Middle Aged ; Pleural Neoplasms/*enzymology/*genetics ; *Polymorphism, Single Nucleotide ; Risk ; Xenobiotics/metabolism ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer mostly attributable to asbestos exposure. Many polymorphic genes encoding for xenobiotic and oxidative metabolism enzymes (XME) or involved in genome stability (GS) can modulate individual MPM risk in exposed populations. An association study was carried out in a case-control setting including 119 MPM patients and two groups of referent subjects (104 with and 695 without documented asbestos exposure). Forty-eight polymorphisms in XME genes and 75 in GS-genes were evaluated. Statistical analysis revealed some significant associations of studied polymorphisms with MPM risk, but most of them disappeared after applying Bonferroni correction (new threshold for statistical significance: p=4.07 x 10(-4)). On the other hand, the nucleotidic change 282C>T within NAT2 held the statistical significance (OR=3.54; 95% CI 1.75-7.16; p=0.0002), reinforcing existing evidences that describe genetic polymorphisms of NAT2 possibly involved in the etiology of the MPM.}, } @article {pmid19749604, year = {2009}, author = {Pintos, J and Parent, ME and Case, BW and Rousseau, MC and Siemiatycki, J}, title = {Risk of mesothelioma and occupational exposure to asbestos and man-made vitreous fibers: evidence from two case-control studies in Montreal, Canada.}, journal = {Journal of occupational and environmental medicine}, volume = {51}, number = {10}, pages = {1177-1184}, doi = {10.1097/JOM.0b013e3181b68cef}, pmid = {19749604}, issn = {1536-5948}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Case-Control Studies ; Female ; Glass ; Humans ; Lung Neoplasms/*etiology ; Male ; Mesothelioma/*etiology ; Middle Aged ; Mineral Fibers/*adverse effects ; Occupational Exposure/*adverse effects ; Odds Ratio ; Quebec ; }, abstract = {OBJECTIVE: To examine the effects of exposure to occupational asbestos and man-made vitreous fibers (MMVF) across a wide range of occupations on risk of mesothelioma.

METHODOLOGY: Two population-based case-control studies (1979-1986 and 1996-2001) provided 35 histologically confirmed mesothelioma cases and 1965 controls. A detailed job history was obtained to evaluate occupational exposure to many agents, including asbestos and MMVF.

RESULTS: The mesothelioma odds ratio for exposure to any asbestos type was 3.7 (95% confidence interval = 1.7 to 7.8). The subset exposed to amphibole fibers experienced an odds ratio = 7.0 (95% confidence interval = 2.7 to 18.5). Effects of MMVF could not be disentangled from those of asbestos.

DISCUSSION: In workers with exposure levels lower than in most historical cohort studies and across a wide range of industries, a strong association was found between asbestos, especially when it was amphibole, and mesothelioma.}, } @article {pmid19746156, year = {2009}, author = {van der Most, RG and Currie, AJ and Cleaver, AL and Salmons, J and Nowak, AK and Mahendran, S and Larma, I and Prosser, A and Robinson, BW and Smyth, MJ and Scalzo, AA and Degli-Esposti, MA and Lake, RA}, title = {Cyclophosphamide chemotherapy sensitizes tumor cells to TRAIL-dependent CD8 T cell-mediated immune attack resulting in suppression of tumor growth.}, journal = {PloS one}, volume = {4}, number = {9}, pages = {e6982}, pmid = {19746156}, issn = {1932-6203}, mesh = {Animals ; Antineoplastic Agents/*pharmacology ; Apoptosis ; CD8-Positive T-Lymphocytes/drug effects/*immunology ; Cell Line, Tumor ; Cyclophosphamide/*pharmacology ; Female ; Immunotherapy/methods ; Interferon-gamma/metabolism ; Killer Cells, Natural/cytology ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasms/immunology/*therapy ; TNF-Related Apoptosis-Inducing Ligand/*metabolism ; }, abstract = {BACKGROUND: Anti-cancer chemotherapy can be simultaneously lymphodepleting and immunostimulatory. Pre-clinical models clearly demonstrate that chemotherapy can synergize with immunotherapy, raising the question how the immune system can be mobilized to generate anti-tumor immune responses in the context of chemotherapy.

METHODS AND FINDINGS: We used a mouse model of malignant mesothelioma, AB1-HA, to investigate T cell-dependent tumor resolution after chemotherapy. Established AB1-HA tumors were cured by a single dose of cyclophosphamide in a CD8 T cell- and NK cell-dependent manner. This treatment was associated with an IFN-alpha/beta response and a profound negative impact on the anti-tumor and total CD8 T cell responses. Despite this negative effect, CD8 T cells were essential for curative responses. The important effector molecules used by the anti-tumor immune response included IFN-gamma and TRAIL. The importance of TRAIL was supported by experiments in nude mice where the lack of functional T cells could be compensated by agonistic anti-TRAIL-receptor (DR5) antibodies.

CONCLUSION: The data support a model in which chemotherapy sensitizes tumor cells for T cell-, and possibly NK cell-, mediated apoptosis. A key role of tumor cell sensitization to immune attack is supported by the role of TRAIL in tumor resolution and explains the paradox of successful CD8 T cell-dependent anti-tumor responses in the absence of CD8 T cell expansion.}, } @article {pmid19738519, year = {2009}, author = {Griniatsos, J and Sougioultzis, S and Dimitriou, N and Vamvakopoulou, V and Alexandrou, P and Kyriakou, V and Tzioufas, A and Papalambros, E and Tzivras, M}, title = {Diffuse malignant peritoneal mesothelioma presenting as intestinal obstruction.}, journal = {Southern medical journal}, volume = {102}, number = {10}, pages = {1061-1064}, doi = {10.1097/SMJ.0b013e3181b671ef}, pmid = {19738519}, issn = {1541-8243}, mesh = {Adult ; Fatal Outcome ; Humans ; Ileostomy ; Intestinal Obstruction/*etiology ; Male ; Mesothelioma/*diagnosis/surgery ; Middle Aged ; Peritoneal Neoplasms/*diagnosis/surgery ; }, abstract = {Diffuse malignant peritoneal mesothelioma (DMPM) represents 90% of all peritoneal forms of mesothelioma. It affects mainly patients 50-69 years old. In 50% of cases there is a history of asbestos exposure. The clinical presentation of the disease is not characteristic: nonspecific abdominal pain, weight loss, and abdominal distension are common. Ascites occurs in 90% of the patients. Bowel obstruction is a late manifestation. We present three patients with DMPM, without a history of asbestos exposure and without ascites, who presented with complete bowel obstruction. All patients underwent emergency operations, and palliative surgical procedures were performed. Each patient died within 3 to 6 months postoperatively.}, } @article {pmid19736192, year = {2009}, author = {Ray, M and Kindler, HL}, title = {Malignant pleural mesothelioma: an update on biomarkers and treatment.}, journal = {Chest}, volume = {136}, number = {3}, pages = {888-896}, doi = {10.1378/chest.08-2665}, pmid = {19736192}, issn = {1931-3543}, mesh = {Biomarkers, Tumor/*analysis ; Humans ; Mesothelioma/diagnosis/epidemiology/pathology/*therapy ; Neoplasm Staging ; Pleural Neoplasms/diagnosis/epidemiology/pathology/*therapy ; Prognosis ; }, abstract = {Although the insulating properties of asbestos have been known for millennia, the link between asbestos exposure and mesothelioma was not recognized until 1960, when it was first described in South African asbestos miners. The incidence of mesothelioma parallels asbestos usage with a latency of 20 to 40+ years; thus, patient numbers are declining in the United States but rising in the developing world. Radiation, genetics, and possibly simian virus 40 are less common causes. Diagnosis can be challenging, since the results of pleural fluid cytology testing are often negative despite repeated sampling. No staging system adequately predicts prognosis in the unresected patient. Newly described biomarkers, including soluble mesothelin-related peptide, megakaryocyte potentiation factor, and osteopontin, may predict which asbestos-exposed individuals will develop mesothelioma, and may prove useful in assessing response to treatment. Since surgery cannot eradicate all residual microscopic disease, a multimodality approach is encouraged. Metaanalysis suggests that pleurectomy/decortication may achieve outcomes similar to those of extrapleural penumonectomy. The standard first-line chemotherapy for unresectable disease is pemetrexed plus cisplatin. This combination improves response, survival, time to progression, pulmonary function, and disease-related symptoms. Carboplatin is often substituted, with similar results. Other active agents include raltitrexed, gemcitabine, and vinorelbine. Novel agents in clinical trials include inhibitors of the epidermal growth factor receptor, vascular endothelial growth factor, mesothelin, and histone deacetylases. Although disappointing results of early trials did not confirm promising preclinical data, recent studies have suggested that some novel agents may be effective. As we learn more about mesothelioma biology, molecularly targeted agents may become treatment options.}, } @article {pmid19731971, year = {2009}, author = {Lee, SF and O'Connor, MM and Chapman, Y and Hamilton, V and Francis, K}, title = {A very public death: dying of mesothelioma and asbestos-related lung cancer (M/ARLC) in the Latrobe Valley, Victoria, Australia.}, journal = {Rural and remote health}, volume = {9}, number = {3}, pages = {1183}, pmid = {19731971}, issn = {1445-6354}, mesh = {Asbestos/*adverse effects/poisoning ; Caregivers ; Female ; Health Services Needs and Demand ; Humans ; Interviews as Topic ; Lung Neoplasms/*etiology ; Male ; Mesothelioma/etiology/*mortality ; Occupational Exposure/adverse effects ; Palliative Care ; Rural Health ; *Terminally Ill ; Victoria/epidemiology ; }, abstract = {INTRODUCTION: It is anticipated that in Australia the number of cases of mesothelioma will continue to rise significantly over the next 15 years with power station workers having a risk second only to asbestos mill workers. Mesothelioma responds poorly to treatment and is almost always fatal, yet there have been few studies related to the palliative care needs of this diagnostic group and none focussing on the Latrobe Valley, Victoria, Australia. The aims of this pilot study were to identify common issues and to explore the needs and experiences of people with mesothelioma and asbestos-related lung cancer (M/ARLC), their carers, and service providers in the Latrobe Valley community, in particular in relation to palliative care.

METHODS: The study employed a case study design using in-depth interviews, media reports, local authority and employer reports and historical data, which were content analysed. The constant comparative method was used to identify common themes and issues.

RESULTS: The Latrobe Valley is the fourth largest regional area in Victoria. The electricity industry and brown coal mining at the town of Yallourn were the primary industries. Former power workers are contracting mesothelioma at a rate seven times the national average. A total of 13 participants from the Latrobe Valley were interviewed, comprising five key stakeholders who were local legal and healthcare providers; two people who had been diagnosed with mesothelioma; and six family carers. Most people with M/ARLC in the Latrobe Valley are older males who were employed by the electricity and related industries, while their carers are mostly female wives and daughters. There were three major themes identified in the data: illness experience; carer and family roles; and services and service gaps. The results indicated that those with M/ARLC and their families experience diagnosis and treatment as being filled with unpredictability and fear. The older males with M/ARLC were characterised as stoic and reluctant to seek help, contributing to a delayed diagnosis. However, their rural health services compounded these delays because of the unpredictability of health professional availability. Although there are some cancer treatment and legal services locally, people with M/ARLC are often required to travel to metropolitan services for care and advice. The effort and time required to seek compensation at a time of declining health was particularly burdensome. Participants expressed the tension between feelings of loyalty to their employers and anger at the perceived betrayal of the same employers, who were reported to have ignored asbestos warnings. Access to palliative care was delayed by a discomfort associated with acknowledgement of dying and resulted in poor symptom control and a lack of support to significantly burdened carers. People with M/ARLC have a strong desire to die at home but issues of rurality, isolation and late referral to palliative care services often complicate their care.

CONCLUSIONS: This pilot study explored the needs of people with M/ARLC in the Latrobe Valley and the results indicated that their experience is complicated by unpredictability, lack of information and the rural location. The study recommended that innovative models of care be investigated to improve communication and continuity of care in the Latrobe Valley community, in addition to the barriers and enablers to local health and legal service provision. Further, the study indicates that a comprehensive education strategy for local health providers and community members, and strategies to prevent and manage volunteer and health professional burnout are needed.}, } @article {pmid19730396, year = {2009}, author = {Lipworth, L and La Vecchia, C and Bosetti, C and McLaughlin, JK}, title = {Occupational exposure to rock wool and glass wool and risk of cancers of the lung and the head and neck: a systematic review and meta-analysis.}, journal = {Journal of occupational and environmental medicine}, volume = {51}, number = {9}, pages = {1075-1087}, doi = {10.1097/JOM.0b013e3181b35125}, pmid = {19730396}, issn = {1536-5948}, mesh = {Adult ; Environmental Monitoring ; Epidemiological Monitoring ; Female ; Head and Neck Neoplasms/epidemiology/*etiology/physiopathology ; Humans ; Incidence ; Lung Neoplasms/epidemiology/*etiology/physiopathology ; Male ; Middle Aged ; Mineral Fibers/*adverse effects ; Occupational Diseases/epidemiology/*etiology/physiopathology ; Occupational Exposure/*adverse effects ; *Occupational Health ; Risk Assessment ; Survival Analysis ; United States ; }, abstract = {OBJECTIVE: To conduct a review and meta-analysis of risks of cancers of the lung and head and neck (HN) from exposure to rock wool (RW) and glass wool (GW).

METHODS: We performed a systematic review and meta-analysis of risk estimates of lung and HN cancer in epidemiologic studies of workers exposed to man-made vitreous fibers (MMVF), specifically RW and GW.

RESULTS: Sixteen estimates of lung cancer risk yielded a summary relative risk (RR) of 1.21 (95% CI = 1.11 to 1.32, based on 1662 exposed cases). Corresponding RRs were 1.26 (95% CI = 1.10 to 1.44) in studies of production workers (with similar risk for RW and GW workers), 1.06 (95% CI = 0.77 to 1.48) in studies of end users, and 1.18 (95% CI = 0.98 to 1.42) in community-based studies. The summary RR for HN cancer was 1.36 (95% CI = 1.13 to 1.63, 414 exposed cases). With a few exceptions, all studies that assessed the risk of lung or HN cancer according to various indices of MMVF exposure failed to detect a dose-risk relation. There was limited evidence of a confounding effect of tobacco smoking. No clear excess of pleural mesothelioma has been reported in MMVF-exposed workers.

CONCLUSIONS: Despite a small elevation in RR for lung cancer among MMVF production workers, the lack of excess risk among end users, the absence of any dose-risk relation, the likelihood of detection bias, and the potential for residual confounding by smoking and asbestos exposure argue against a carcinogenic effect of MMVF, RW, or GW at this time. Similar conclusions apply to HN cancer risk among workers exposed to MMVF.}, } @article {pmid19728322, year = {2009}, author = {Kumagai, S and Kurumatani, N}, title = {Asbestos fiber concentration in the area surrounding a former asbestos cement plant and excess mesothelioma deaths in residents.}, journal = {American journal of industrial medicine}, volume = {52}, number = {10}, pages = {790-798}, doi = {10.1002/ajim.20743}, pmid = {19728322}, issn = {1097-0274}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Cohort Studies ; Confidence Intervals ; Construction Materials/*toxicity ; Environmental Exposure/*adverse effects ; Female ; Humans ; Japan/epidemiology ; Male ; Mesothelioma/epidemiology/etiology/*mortality ; Middle Aged ; Regression Analysis ; Risk Assessment ; Risk Factors ; Sex Factors ; Statistics as Topic ; }, abstract = {BACKGROUND: Many persons who had lived near a former asbestos cement plant (AC plant) died from mesothelioma in Amagasaki city, Japan.

METHODS: Asbestos fiber concentration in the area surrounding the AC plant was estimated so that the female mesothelioma death number predicted by a mathematical model was the same as the observed excess death number. We used the estimated asbestos fiber concentration to predict the excess mesothelioma deaths from 1970 to 2049.

RESULTS: In a grid just south of the AC plant, the fiber concentration was estimated to be more than 3 f/ml for K(M) (asbestos potency factor for mesothelioma) of 7.75 x 10(-9). An uncertainty factor of five yields a K(M) range 1.55 x 10(-9) to 38.8 x 10(-9); these in turn correspond to fiber concentrations of 15 and 0.6 f/ml. For K(M) = 7.75 x 10(-9), grid units with higher fiber concentrations than 0.01 f/ml were estimated to extend 4.1 km (95% CI: 3.8-4.4 km) south-southwest of the plant. Over the 80-year study period (1970 to 2049), we predicted that the exposure under study will cause 346 excess mesothelioma deaths with range of 296 to 382 deaths.

CONCLUSIONS: This prediction suggests that considerable medical resources will be needed through 2049 as a result of past asbestos exposure in this region.}, } @article {pmid19722279, year = {2009}, author = {Song, J and Park, JK and Lee, JJ and Choi, YS and Ryu, KS and Kim, JH and Kim, E and Lee, KJ and Jeon, YH and Kim, EE}, title = {Structure and interaction of ubiquitin-associated domain of human Fas-associated factor 1.}, journal = {Protein science : a publication of the Protein Society}, volume = {18}, number = {11}, pages = {2265-2276}, pmid = {19722279}, issn = {1469-896X}, mesh = {Adaptor Proteins, Signal Transducing/*chemistry/genetics/metabolism ; Amino Acid Sequence ; Apoptosis Regulatory Proteins ; Binding Sites/genetics ; Cell Line ; Crystallography, X-Ray ; Humans ; Models, Molecular ; Molecular Sequence Data ; Nuclear Magnetic Resonance, Biomolecular ; Protein Binding/genetics ; Protein Structure, Tertiary/*genetics ; Sequence Alignment ; Ubiquitin/*chemistry/metabolism ; Ubiquitins/chemistry/metabolism ; }, abstract = {Fas-associated factor (FAF)-1 is a multidomain protein that was first identified as a member of the Fas death-inducing signaling complex, but later found to be involved in various biological processes. Although the exact mechanisms are not clear, FAF1 seems to play an important role in cancer, asbestos-induced mesotheliomas, and Parkinson's disease. It interacts with polyubiquitinated proteins, Hsp70, and p97/VCP (valosin-containing protein), in addition to the proteins of the Fas-signaling pathway. We have determined the crystal structure of the ubiquitin-associated domain of human FAF1 (hFAF1-UBA) and examined its interaction with ubiquitin and ubiquitin-like proteins using nuclear magnetic resonance. hFAF1-UBA revealed a canonical three-helical bundle that selectively binds to mono- and di-ubiquitin (Lys48-linked), but not to SUMO-1 (small ubiquitin-related modifier 1) or NEDD8 (neural precursor cell expressed, developmentally down-regulated 8). The interaction between hFAF1-UBA and di-ubiquitin involves hydrophobic interaction accompanied by a transition in the di-ubiquitin conformation. These results provide structural insight into the mechanism of polyubiquitin recognition by hFAF1-UBA.}, } @article {pmid19708533, year = {2009}, author = {Ikeda, S and Takabe, K and Suzuki, K}, title = {[Epidermal growth factor receptor aberrations in malignant mesotheliomas].}, journal = {Rinsho byori. The Japanese journal of clinical pathology}, volume = {57}, number = {7}, pages = {644-650}, pmid = {19708533}, issn = {0047-1860}, mesh = {Antineoplastic Agents/therapeutic use ; ErbB Receptors/*analysis/genetics ; Gefitinib ; Humans ; Lung Neoplasms/chemistry ; Mesothelioma/*chemistry/drug therapy ; Quinazolines/therapeutic use ; }, abstract = {Recently, the incidence of malignant mesothelioma has been increasing from such causes as asbestos exposure. In this study, we compared Epidermal Growth Factor Receptor (EGFR) aberrations in malignant mesotheliomas to those in lung cancers, to determine whether gefitinib may be useful for treatment of a malignant mesothelioma. We investigated 15 cases with malignant mesothelioma, 5 with lung cancer, and 10 with cell block from pleural effusion. In the malignant mesothelioma and lung cancer cases, we also examined the expression of EGFR by immunostaining using two kinds of anti-EGFR antibodies. In addition, we searched for ser473 p-Akt (p-Akt), which is activated by EGFR, and Epithelial Membrane Antigen (EMA), which is generally used as differential diagnosis marker of mesothelial cells. Furthermore, we examined the expressions of EGFR and EMA in benign mesothelial cells in cell blocks. Numerical abnormalities of the EGFR gene were examined by chromosome in situ hybridization, while the exonl9 and exon21 gene mutations of EGFR were examined using PCR-heteroduplex and PCR-RFLP methods, respectively. Our results showed that the EGFR protein was expressed in most of the malignant mesotheliomas in the same manner as in the lung cancer specimens. On the other hand, p-Akt was expressed in all cases (100%) of lung cancer, whereas that expression was seen in only 1 of 15 (7%) of malignant mesothelioma cases. As for EGFR gene abnormalities, a mutation was found in 1 (20%) and gene amplification in 2 (40%) lung cancer cases, while in malignant mesothelioma cases, amplification was found in 2 cases (13%) and no mutation was detected in any. Moreover, in staining results with one of the antibodies, the expression of EGFR was not different between malignant mesothelioma and non-neoplastic mesothelial cells. We observed EGFR expression at a high frequency in both the malignant mesothelioma and lung cancer specimens. However, distinct differences were detected between them in regard to EGFR gene abnormalities and the expression of p-Akt. These results suggest that it would be rare for a patient with malignant mesothelioma to benefit from gefitinib treatment.}, } @article {pmid19698846, year = {2009}, author = {Yan, TD and Boyer, M and Tin, MM and Wong, D and Kennedy, C and McLean, J and Bannon, PG and McCaughan, BC}, title = {Extrapleural pneumonectomy for malignant pleural mesothelioma: outcomes of treatment and prognostic factors.}, journal = {The Journal of thoracic and cardiovascular surgery}, volume = {138}, number = {3}, pages = {619-624}, doi = {10.1016/j.jtcvs.2008.12.045}, pmid = {19698846}, issn = {1097-685X}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Carboplatin/administration & dosage ; Chemotherapy, Adjuvant ; Cisplatin/administration & dosage ; Cohort Studies ; Female ; Follow-Up Studies ; Glutamates/administration & dosage ; Guanine/administration & dosage/analogs & derivatives ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Male ; Mesothelioma/diagnosis/mortality/secondary/*surgery ; Middle Aged ; Multivariate Analysis ; Pemetrexed ; Pleural Neoplasms/diagnosis/mortality/*surgery ; Pneumonectomy/*methods ; Positron-Emission Tomography ; Postoperative Care ; Prognosis ; Radiotherapy, Adjuvant ; Survival Rate ; Treatment Outcome ; }, abstract = {OBJECTIVE: This study aimed to evaluate the perioperative and long-term outcomes associated with extrapleural pneumonectomy for patients with malignant pleural mesothelioma.

METHODS: From October 1994 to April 2008, 70 patients were selected for extrapleural pneumonectomy. Univariate analysis was performed using the Kaplan-Meier method and compared using the log-rank test. Multivariate analysis with entering and removing limits of P less than .10 and P greater than .05, respectively, was used. The prognostic factors included age, gender, side of disease, asbestos exposure, histology, positron emission tomography, date of surgery, neoadjuvant chemotherapy, completeness of cytoreduction, lymph node involvement, perioperative morbidity, adjuvant radiotherapy, and pemetrexed-based chemotherapy.

RESULTS: The mean age of patients was 55 years (standard deviation = 10). Fifty-eight patients had epithelial tumors. Six patients received neoadjuvant chemotherapy, 28 patients received adjuvant radiotherapy, and 16 patients received postoperative pemetrexed-based chemotherapy. Forty-four patients had no lymph node involvement. The perioperative morbidity and mortality were 37% and 5.7%, respectively. Complications included hemothorax (n = 7), atrial fibrillation (n = 6), empyema (n = 4), bronchopulmonary fistula (n = 3), right-sided heart failure (n = 2), pneumonia (n = 1), constrictive pericarditis (n = 1), acute pulmonary edema (n = 1), small bowel herniation (n = 1), and disseminated intravascular coagulopathy (n = 1). The median survival was 20 months, with a 3-year survival of 30%. Asbestos exposure, negative lymph node involvement, and receipt of adjuvant radiation or postoperative pemetrexed-based chemotherapy were associated with improved survival on both univariate and multivariate analyses.

CONCLUSION: The present study supports the use of extrapleural pneumonectomy-based multimodal therapy in carefully selected patients with malignant pleural mesothelioma.}, } @article {pmid19670258, year = {2009}, author = {Dement, JM and Ringen, K and Welch, LS and Bingham, E and Quinn, P}, title = {Mortality of older construction and craft workers employed at Department of Energy (DOE) nuclear sites.}, journal = {American journal of industrial medicine}, volume = {52}, number = {9}, pages = {671-682}, doi = {10.1002/ajim.20729}, pmid = {19670258}, issn = {1097-0274}, mesh = {Adult ; Aged ; Construction Materials ; Female ; Humans ; Male ; Metallurgy/statistics & numerical data ; Middle Aged ; Neoplasms/*mortality ; *Nuclear Energy ; Occupational Exposure/*adverse effects/statistics & numerical data ; *Population Surveillance ; United States/epidemiology ; }, abstract = {BACKGROUND: The U.S. Department of Energy (DOE) established medical screening programs at the Hanford Nuclear Reservation, Oak Ridge Reservation, the Savannah River Site, and the Amchitka site starting in 1996. Workers participating in these programs have been followed to determine their vital status and mortality experience through December 31, 2004.

METHODS: A cohort of 8,976 former construction workers from Hanford, Savannah River, Oak Ridge, and Amchitka was followed using the National Death Index through December 31, 2004, to ascertain vital status and causes of death. Cause-specific standardized mortality ratios (SMRs) were calculated based on US death rates.

RESULTS: Six hundred and seventy-four deaths occurred in this cohort and overall mortality was slightly less than expected (SMR = 0.93, 95% CI = 0.86-1.01), indicating a "healthy worker effect." However, significantly excess mortality was observed for all cancers (SMR = 1.28, 95% CI = 1.13-1.45), lung cancer (SMR = 1.54, 95% CI = 1.24-1.87), mesothelioma (SMR = 5.93, 95% CI = 2.56-11.68), and asbestosis (SMR = 33.89, 95% CI = 18.03-57.95). Non-Hodgkin's lymphoma was in excess at Oak Ridge and multiple myeloma was in excess at Hanford. Chronic obstructive pulmonary disease (COPD) was significantly elevated among workers at the Savannah River Site (SMR = 1.92, 95% CI = 1.02-3.29).

CONCLUSIONS: DOE construction workers at these four sites were found to have significantly excess risk for combined cancer sites included in the Department of Labor' Energy Employees Occupational Illness Compensation Program (EEOCIPA). Asbestos-related cancers were significantly elevated.}, } @article {pmid19664483, year = {2009}, author = {Salahudeen, HM and Hoey, ET and Robertson, RJ and Darby, MJ}, title = {CT appearances of pleural tumours.}, journal = {Clinical radiology}, volume = {64}, number = {9}, pages = {918-930}, doi = {10.1016/j.crad.2009.03.010}, pmid = {19664483}, issn = {1365-229X}, mesh = {Adenocarcinoma/diagnostic imaging/secondary ; Aged ; Asbestos/adverse effects ; Female ; Fibroma/diagnostic imaging ; Humans ; Lipoma/diagnostic imaging ; Lymphoma/diagnostic imaging ; Male ; Mesothelioma/diagnostic imaging/pathology ; Neoplasm Staging/methods ; Occupational Exposure/adverse effects ; Pleura/anatomy & histology/diagnostic imaging ; Pleural Neoplasms/*diagnostic imaging/pathology/secondary ; Sarcoma/diagnostic imaging ; *Tomography, X-Ray Computed ; }, abstract = {Computed tomography (CT) is the imaging technique of choice for characterizing pleural masses with respect to their location, composition, and extent. CT also provides important information regarding invasion of the chest wall and surrounding structures. A spectrum of tumours can affect the pleura of which metastatic adenocarcinoma is the commonest cause of malignant pleural disease, while malignant mesothelioma is the most common primary pleural tumour. Certain CT features help differentiate benign from malignant processes. This pictorial review highlights the salient CT appearances of a range of tumours that may affect the pleura.}, } @article {pmid19650718, year = {2009}, author = {Price, B and Ware, A}, title = {Time trend of mesothelioma incidence in the United States and projection of future cases: an update based on SEER data for 1973 through 2005.}, journal = {Critical reviews in toxicology}, volume = {39}, number = {7}, pages = {576-588}, doi = {10.1080/10408440903044928}, pmid = {19650718}, issn = {1547-6898}, mesh = {Female ; Forecasting ; Humans ; Incidence ; Male ; Mesothelioma/*epidemiology/etiology ; Peritoneal Neoplasms/*epidemiology/etiology ; Pleural Neoplasms/*epidemiology/etiology ; SEER Program/*statistics & numerical data ; United States/epidemiology ; }, abstract = {The time trend of mesothelioma incidence and projections of future cases provide useful information for analyzing proposed public health interventions where asbestos exposure may be an issue, evaluating regulatory proposals, and estimating the remaining potential costs of programs to compensate individuals with asbestos-related diseases. We used the April 2008 release of Surveillance, Epidemiology, and End Results (SEER) data, which covers 1973 through 2005, to analyze the time trends in age-adjusted mesothelioma incidence and to estimate an age and birth-cohort model to project the number of future mesothelioma cases. The increase in the number of SEER cancer registries from 13 to 17 in 2000 had little effect on the time pattern of age-adjusted mesothelioma incidence, and the pattern over time of pleural mesothelioma was indistinguishable from the pattern for total mesothelioma defined as sum of pleural and peritoneal cases. Our analysis suggests that the SEER registries viewed as a sample of the U.S. population over-represents high mesothelioma incidence, a fact that we accounted for in our projections. For 2008 we estimate approximately 2,400 cases, with asbestos the likely cause in 58%. We project that asbestos will no longer be a factor in mesothelioma cases after the year 2042. For 2008 through 2042, we estimate slightly more than 68,000 total cases, with asbestos the likely cause in 34%.}, } @article {pmid19644223, year = {2009}, author = {Nakamura, E and Makishima, A and Hagino, K and Okabe, K}, title = {Accumulation of radium in ferruginous protein bodies formed in lung tissue: association of resulting radiation hotspots with malignant mesothelioma and other malignancies.}, journal = {Proceedings of the Japan Academy. Series B, Physical and biological sciences}, volume = {85}, number = {7}, pages = {229-239}, pmid = {19644223}, issn = {1349-2896}, mesh = {Aged ; Asbestos/metabolism/toxicity ; DNA Damage ; Female ; Ferritins/*metabolism ; Gadolinium/metabolism ; Humans ; Lung/drug effects/metabolism/pathology/radiation effects ; Lung Neoplasms/chemically induced/etiology/*metabolism/*pathology ; Male ; Mesothelioma/chemically induced/etiology/*metabolism/*pathology ; Middle Aged ; Neoplasms, Radiation-Induced/*metabolism/pathology ; Proteins/*metabolism ; Radium/*metabolism ; Trace Elements/metabolism ; }, abstract = {While exposure to fibers and particles has been proposed to be associated with several different lung malignancies including mesothelioma, the mechanism for the carcinogenesis is not fully understood. Along with mineralogical observation, we have analyzed forty-four major and trace elements in extracted asbestos bodies (fibers and proteins attached to them) with coexisting fiber-free ferruginous protein bodies from extirpative lungs of individuals with malignant mesothelioma. These observations together with patients' characteristics suggest that inhaled iron-rich asbestos fibers and dust particles, and excess iron deposited by continuous cigarette smoking would induce ferruginous protein body formation resulting in ferritin aggregates in lung tissue. Chemical analysis of ferruginous protein bodies extracted from lung tissues reveals anomalously high concentrations of radioactive radium, reaching millions of times higher concentration than that of seawater. Continuous and prolonged internal exposure to hotspot ionizing radiation from radium and its daughter nuclides could cause strong and frequent DNA damage in lung tissue, initiate different types of tumour cells, including malignant mesothelioma cells, and may cause cancers.}, } @article {pmid19642427, year = {2009}, author = {Scherpereel, A}, title = {[Malignant mesothelioma].}, journal = {La Revue du praticien}, volume = {59}, number = {6}, pages = {751-755}, pmid = {19642427}, issn = {0035-2640}, mesh = {Asbestos/adverse effects ; Decision Trees ; Humans ; Mass Screening ; Mesothelioma/*diagnosis/*therapy ; Pleural Neoplasms/*diagnosis/*therapy ; }, abstract = {Malignant pleural mesothelioma (MPM) is an agressive and rare tumour, but with increasing incidence linked to previous exposure to asbestos fibers, its main etiological factor. The interest for this cancer has been stimulated by recent improvements in the diagnosis and in the treatment of mesothelioma, including new cytotoxic drugs and multimodal treatment, associating chemotherapy, radical surgery and radiotherapy in prospective, randomised and multicentric trials. The management of MPM is now better defined by the guidelines from the experts Conference of the Société de Pneumologie de Langue Française in 2005, actualised this year by the European Respiratory Society.}, } @article {pmid19636166, year = {2009}, author = {Zona, A and Bruno, C}, title = {Health surveillance for subjects with past exposure to asbestos: from international experience and Italian regional practices to a proposed operational model.}, journal = {Annali dell'Istituto superiore di sanita}, volume = {45}, number = {2}, pages = {147-161}, pmid = {19636166}, issn = {2384-8553}, mesh = {Asbestos/*adverse effects ; Carcinogens/*toxicity ; Humans ; Italy/epidemiology ; Lung Neoplasms/chemically induced/diagnosis/epidemiology ; Mesothelioma/chemically induced/diagnosis/epidemiology ; Models, Statistical ; Occupational Exposure/*statistics & numerical data ; Population Surveillance ; }, abstract = {The authors have examined Italian and international approaches to the health surveillance of subjects with past occupational exposure to asbestos, with special emphasis on the practices adopted by some Italian regional governments. The principal theoretic features of a surveillance programme, such as its usefulness in terms of oncological prevention, have been described and an operational proposal has been put forward for the consideration of interested health operators.}, } @article {pmid19635740, year = {2010}, author = {Manzini, VP and Recchia, L and Cafferata, M and Porta, C and Siena, S and Giannetta, L and Morelli, F and Oniga, F and Bearz, A and Torri, V and Cinquini, M}, title = {Malignant peritoneal mesothelioma: a multicenter study on 81 cases.}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {21}, number = {2}, pages = {348-353}, doi = {10.1093/annonc/mdp307}, pmid = {19635740}, issn = {1569-8041}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Comorbidity ; Female ; Humans ; Italy/epidemiology ; Male ; Mesothelioma/*diagnosis/*etiology ; Middle Aged ; Peritoneal Neoplasms/*diagnosis/epidemiology/*etiology/therapy ; Prognosis ; Retrospective Studies ; Survival Analysis ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Malignant peritoneal mesothelioma (MPM) is a rare disease characterized by a difficult diagnosis, different types of presentation, variable course and poor prognosis.

MATERIALS AND METHODS: Eighty-one patients with MPM observed in 14 Italian oncology institutions from 1982 to 2007 have been examined with the aim of delineating the history of MPM.

RESULTS: Presentation symptoms were ascites, abdominal pain, asthenia, weight loss, anorexia, abdominal mass, fever, diarrhea and vomiting in various associations. Computed tomography scan and echotomography signs were ascites, abdominal mass and peritoneal thickening. Peritoneal fluid cytology (61 cases) was positive for mesothelioma in 31 and for malignancy, not mesothelioma, in 13. Laparoscopy was carried out in 40 cases and laparotomy in 36. Thrombocytosis was present in 59 cases. Associated tumors diagnosed during the lifetime were colorectal cancer in two cases and cheek carcinoma, thyroid carcinoma, tongue carcinoma, bladder carcinoma and testicular seminoma. Thirty patients were treated with surgery and 45 with chemotherapy. The median survival time from diagnosis is 13 months. Ascites, fever and vomiting were significative variables at presentation; only vomiting holds significance in a multivariate analysis.

CONCLUSIONS: MPM is a disease with various types of presentation, frequently associated with thrombocytosis, sometimes with other tumors. Survival and diagnosis time can differ in various types of MPM. Prognosis is poor.}, } @article {pmid19633479, year = {2009}, author = {Tanzi, S and Tiseo, M and Internullo, E and Cacciani, G and Capra, R and Carbognani, P and Rusca, M and Rindi, G and Ardizzoni, A}, title = {Localized malignant pleural mesothelioma: report of two cases.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {4}, number = {8}, pages = {1038-1040}, doi = {10.1097/JTO.0b013e3181a8c874}, pmid = {19633479}, issn = {1556-1380}, mesh = {Aged ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local/*pathology ; Pleural Neoplasms/*pathology/radiotherapy/surgery ; Solitary Fibrous Tumor, Pleural/*pathology/radiotherapy/surgery ; }, abstract = {Localized malignant pleural mesothelioma is very rare tumor disease. There are sporadic reports in the literature showing that this entity has a different biologic behavior compared with diffuse pleural mesothelioma. We report two cases of radically resected localized pleural malignant mesothelioma, with a previous history of asbestos exposure. Both cases showed a microscopic and immunohistochemical findings of malignant mesothelioma, biphasic and sarcomatoid lympho-histiocitoid variant type, respectively, without evidence of diffuse pleural spread. The first is very peculiar case of bilateral localized malignant pleural mesothelioma with complete response to chemotherapy and localized late recurrence, radically resected and treated with adjuvant radiotherapy. The second case revealed as a solitary localized mass, underwent a complete en bloc resection and adjuvant radiotherapy. Both cases demonstrate that the localized malignant mesothelioma should be distinguished from diffuse form and that complete resection is associated with good prognosis.}, } @article {pmid19627545, year = {2009}, author = {Ogata, S and Hiroi, S and Tominaga, A and Aida, S and Kobayashi, A and Tamura, K and Abe, Y and Kawai, T}, title = {Malignant pleural mesothelioma initially diagnosed on cervical lymph node biopsy.}, journal = {Pathology international}, volume = {59}, number = {8}, pages = {592-594}, doi = {10.1111/j.1440-1827.2009.02412.x}, pmid = {19627545}, issn = {1440-1827}, mesh = {Biopsy ; Diuretics/therapeutic use ; Humans ; Immunohistochemistry ; Lymph Nodes/*pathology/surgery ; Lymphatic Metastasis/*pathology ; Male ; Mesothelioma/*diagnosis ; Middle Aged ; Neck/pathology ; Pleural Effusion, Malignant/drug therapy/etiology ; Pleural Neoplasms/*diagnosis ; Positron-Emission Tomography ; }, abstract = {Reported herein is a case of malignant pleural mesothelioma, initially diagnosed on cervical lymph node biopsy. A 58-year-old man, without obvious evidence of asbestos exposure, exhibited repeated pleural effusion (cause unclear), which was resolved by diuretics. A neck mass was apparent and was identified pathologically as a lymph node metastasis of malignant mesothelioma. F-18 fluorodeoxyglucose positron emission tomography/CT established the diagnosis of malignant pleural mesothelioma. Two conclusions emerge from this report: (i) cervical lymph node metastasis of pleural mesothelioma, although rare, should be included in differential diagnosis; and (ii) positron emission tomography/CT is useful for establishing a diagnosis of mesothelioma.}, } @article {pmid19627537, year = {2009}, author = {Hiroshima, K and Yusa, T and Kameya, T and Ito, I and Kaneko, K and Kadoyama, C and Kishi, H and Saitoh, Y and Ozaki, D and Itami, M and Iwata, T and Iyoda, A and Kawai, T and Yoshino, I and Nakatani, Y}, title = {Malignant pleural mesothelioma: clinicopathology of 16 extrapleural pneumonectomy patients with special reference to early stage features.}, journal = {Pathology international}, volume = {59}, number = {8}, pages = {537-545}, doi = {10.1111/j.1440-1827.2009.02404.x}, pmid = {19627537}, issn = {1440-1827}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Humans ; Immunohistochemistry ; Male ; Mesothelioma/metabolism/*pathology/surgery ; Middle Aged ; *Neoplasm Staging/methods ; Pleural Neoplasms/metabolism/*pathology/surgery ; Pneumonectomy ; }, abstract = {The earliest pathological events in the development of malignant pleural mesothelioma (MPM) are not understood. The aim of the present study was to elucidate the early histopathological features of MPM. A total of 16 extrapleural MPM pneumonectomy patients were investigated. Early stage mesothelioma was arbitrarily defined as a tumor < or =5 mm in thickness regardless of the nodal status or other organ involvement. Eight of these patients (six with epithelioid, two with biphasic) had early stage mesothelioma by this definition. Macroscopically there was no visible tumor, but the parietal and visceral pleura were thickened and there was focal adhesion between them. Microscopically, the mesothelioma lesions were multifocal and discontinuous on the pleura. In extremely early cases of epithelioid mesothelioma, tumor cells were generally arrayed in a single layer, but papillary proliferation was observed elsewhere. In sarcomatoid mesothelioma, mesothelioma cells proliferated, forming multiple small polypoid nodules on the pleura. Epithelial membrane antigen was helpful to distinguish reactive from neoplastic mesothelium, but glucose transporter-1 was not. Mesothelioma cells disseminate diffusely throughout the parietal and visceral pleura and mediastinal fat tissue before becoming visible. Stage Ia mesothelioma (neoplasm limited to the parietal pleura) would not be observed in daily practice.}, } @article {pmid19618209, year = {2009}, author = {Ruangchira-urai, R and Mark, EJ}, title = {Lymphangiomatoid pattern in diffuse malignant mesothelioma of the pleura: a report of six cases.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {455}, number = {2}, pages = {143-148}, pmid = {19618209}, issn = {1432-2307}, mesh = {Aged ; Aged, 80 and over ; Calbindin 2 ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Keratin-7/genetics/metabolism ; Lymphangioma/diagnosis/metabolism/*pathology ; Male ; Mesothelioma/diagnosis/metabolism/*pathology ; Middle Aged ; Pleural Neoplasms/diagnosis/metabolism/*pathology ; S100 Calcium Binding Protein G/genetics/metabolism ; }, abstract = {The multiplicity of epithelioid and mesenchymal forms of diffuse malignant mesothelioma includes patterns that may mimic another process. Identification of the multiplicity of patterns may help in the diagnosis of diffuse malignant mesothelioma. One pattern that has not been described is lymphangiomatoid. We observed six cases with ovoid or elongated or irregular anastomosing vascular-like spaces lined by flattened cells simulating lymphangioma. The luminal spaces could contain proteinaceous material simulating lymph but not erythrocytes. The cells lining the spaces were mesothelial by immunohistochemical staining. The lymphangiomatoid areas never constituted more than 40% of the area of the tumor on the slides. When seen in more solid areas of tumor, the lymphangiomatoid structures generally did not produce diagnostic difficulty. However, when seen at the edge of solid tumor or forming an irregular nodule or invading into adjacent adipose tissue, these lymphangiomatoid structures could be confusing. All six patients had been exposed to asbestos either by occupation or by spousal exposure. Three patients received chemotherapy. One patient died of diffuse malignant mesothelioma of the pleura.}, } @article {pmid19617842, year = {2009}, author = {Goldberg, M and Luce, D}, title = {The health impact of nonoccupational exposure to asbestos: what do we know?.}, journal = {European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP)}, volume = {18}, number = {6}, pages = {489-503}, pmid = {19617842}, issn = {1473-5709}, mesh = {Asbestos/*adverse effects ; Environmental Exposure/*adverse effects ; Epidemiologic Studies ; *Health Impact Assessment ; Humans ; Lung Neoplasms/*chemically induced ; Mesothelioma/*chemically induced ; Pleural Neoplasms/*chemically induced ; Risk Assessment ; Risk Factors ; }, abstract = {The objective of this study was to examine the epidemiological data that confirm the risks of pleural mesothelioma, lung cancer, and other respiratory damage associated with nonoccupational exposure to asbestos, in circumstances where exposure levels are usually lower than those found in the workplace: domestic and paraoccupational exposure to asbestos-containing material among people living with asbestos workers or near asbestos mines and manufacturing plants, environmental exposure from naturally occurring asbestos in soil, and nonoccupational exposure to asbestos-containing material in buildings. Studies concerning natural asbestos in the environment show that the exposure that begins at birth does not seem to affect the duration of the latency period, but the studies do not show whether early exposure increases susceptibility; they do not suggest that susceptibility differs according to sex. Solid evidence shows an increased risk of mesothelioma among people whose exposure comes from a paraoccupational or domestic source. The risk of mesothelioma associated with exposure as result of living near an industrial asbestos source (mines, mills, asbestos processing plants) is clearly confirmed. No solid epidemiological data currently justify any judgment about the health effects associated with passive exposure in buildings containing asbestos. Most of the studies on nonoccupational sources reported mainly amphibole exposure, but it cannot be ruled out that environmental exposure to chrysotile may also cause cancer. Nonoccupational exposure to asbestos may explain approximately 20% of the mesotheliomas in industrialized countries, but it is does not seem possible to estimate the number of lung cancers caused by these circumstances of exposure.}, } @article {pmid19588825, year = {2009}, author = {Matsuda, E and Okabe, K and Kobayashi, S and Tao, H and Hirazawa, K and Murakami, T and Sugi, K}, title = {[Malignant pleural mesothelioma in which many asbestos bodies were counted in its specimen].}, journal = {Kyobu geka. The Japanese journal of thoracic surgery}, volume = {62}, number = {7}, pages = {552-555}, pmid = {19588825}, issn = {0021-5252}, mesh = {Asbestos/*analysis ; Female ; Humans ; Lung/*chemistry ; Mesothelioma/*metabolism ; Middle Aged ; Pleural Neoplasms/*metabolism ; }, abstract = {A 53-years-old woman was admitted to our hospital because of pleural effusion. She underwent pleural biopsy and diagnosed as mesothelioma. Right extrapleuralpneumonectomy was performed. We counted asbestos bodies in the resected lung. 443,571 asbestos bodies were counted in 1 gram of dry lung. We thought that she was heavily exposed to asbestos. Since high risk of incidence of mesothelioma is suggested among her fellow worker, special investigation is necessary for asbestos exposure.}, } @article {pmid19588722, year = {2009}, author = {O'Connor, M and Lee, S and Chapman, Y and Francis, K and Humphreys, J}, title = {A very public death. Mesothelioma & asbestos-related lung cancer.}, journal = {Australian nursing journal (July 1993)}, volume = {16}, number = {11}, pages = {52-53}, pmid = {19588722}, issn = {1320-3185}, mesh = {Asbestosis/*epidemiology/etiology/therapy ; Coal Mining ; Humans ; Lung Neoplasms/*epidemiology/etiology/therapy ; Mesothelioma/*epidemiology/etiology/therapy ; Needs Assessment/*organization & administration ; Occupational Diseases/*epidemiology/etiology ; Palliative Care/organization & administration ; Pilot Projects ; Victoria/epidemiology ; }, } @article {pmid19585878, year = {2009}, author = {Nemo, A and Boccuzzi, MT and Silvestri, S}, title = {[Asbestos import in Italy: the transit through Livorno harbour from 1957 to 1995].}, journal = {Epidemiologia e prevenzione}, volume = {33}, number = {1-2}, pages = {59-64}, pmid = {19585878}, issn = {1120-9763}, mesh = {Asbestos/*adverse effects ; *Carcinogens ; Humans ; Italy/epidemiology ; Journalism ; Lung Neoplasms/epidemiology/*etiology ; Mesothelioma/epidemiology/*etiology ; Mineral Fibers ; Occupational Diseases/epidemiology/*etiology ; Occupational Exposure/*adverse effects ; Retrospective Studies ; Workplace ; }, abstract = {This work aims to describe quantities, type of packaging and geographical area of origin of the asbestos fibres unloaded in Livorno harbour between 1957 and 1995. Historical data, available for this period, were collected from Il Messaggero Marittimo, a periodical journal dealing with Livorno harbour activities. Collaboration between the local Health and Safety Unit (ASL 6) and the Institute for Study and Prevention of Cancer (ISPO), both Regional Institutions of the National Health Service, made it possible to carry out this work. The computation of the collected data for the whole period allows the description of the quantities, year by year and the assessment of the percentage imported through Livorno on the total tonnage imported in Italy during the same period. The detection of the geographical areas of origin allowed to estimate the quantities subdivided by type of fibre (serpentine/amphiboles). These results will help the historical assessment of occupational asbestos exposure of the Livorno dockers.}, } @article {pmid19585874, year = {2009}, author = {Graziano, G and Bilancia, M and Bisceglia, L and de Nichilo, G and Pollice, A and Assennato, G}, title = {[Statistical analysis of the incidence of some cancers in the province of Taranto 1999-2001].}, journal = {Epidemiologia e prevenzione}, volume = {33}, number = {1-2}, pages = {37-44}, pmid = {19585874}, issn = {1120-9763}, mesh = {Algorithms ; Brain Neoplasms/epidemiology ; Carcinogens, Environmental/*toxicity ; Female ; Humans ; Incidence ; Italy/epidemiology ; Leukemia/epidemiology ; Lung Neoplasms/epidemiology ; Lymphoma, Non-Hodgkin/epidemiology ; Male ; Medical Records ; Mesothelioma/epidemiology ; Neoplasms/chemically induced/*epidemiology ; Pleural Neoplasms/epidemiology ; Poisson Distribution ; Retrospective Studies ; Risk ; Urinary Bladder Neoplasms/epidemiology ; Water Pollutants, Chemical/toxicity ; }, abstract = {OBJECTIVE: to estimate the spatial distribution of risk, in order to assess its correlation to environmental pollution exposure around the large production facilities located in the Taranto area, and to identify high risk areas not previously reported.

SETTING: Italy, Taranto province (581,508 inhabitants).

DESIGN: incidence data in 29 municipalities of the Taranto province were extracted from the Jonico Salentino Cancer Registry (RTJS) for the following cancer sites: lung (ICDX C33-C34); pleura, pleuric mesothelioma (ICDX C45.0); bladder, malignancies only (ICDX C67); brain (ICDX C70-72); non-Hodgkin lymphoma (ICDX C82-85, C96); leukaemia (ICDX C91-5). Age standardized incidence rates for the whole province were computed. High-level risk areas were classified using a Poisson model, computing area-specific p-values associated to the null hypothesis of no increased risk (i.e. relative risk equal to 1). A hierarchical spatial Bayesian model was estimated to strengthen results: specifically two additional variance components, accounting for relative risk spatial autocorrelation and excess heterogeneity respectively, were considered in the model specification. Bayesian mapping of disease incidence allows for the drawing of regularized (smoothed) maps. To adjust for the effect of socio-economic deprivation, a five-variable index was introduced into the model as an ecological covariate.

RESULTS: an increased risk of lung, pleura and bladder cancer was observed among male residents in the city of Taranto (respectively: SIR 1.24, p-value < 0.01; SIR: 2.21, p-value < 0.01; SIR 1.28, p-value < 0.01). For non-Hodgkin lymphoma, a significant value was observed in the city of Taranto for males (SIR 1.46, p-value < 0.01), as well as in the neighbouring area of Pulsano for females (SIR 3.88, p-value < 0.01). An unexpected increased risk of brain cancer was found in both sexe risk (especially among males) of lung, pleura and bladder cancer is likely related to the chemical pollutants and asbestos, due to the presence of many industries and shipyards in the city of Taranto.}, } @article {pmid19581718, year = {2009}, author = {Yada, K and Kohyama, N}, title = {Microstructures and biological influence of environmental exposure of asbestos.}, journal = {Bio-medical materials and engineering}, volume = {19}, number = {2-3}, pages = {231-239}, doi = {10.3233/BME-2009-0585}, pmid = {19581718}, issn = {0959-2989}, mesh = {Asbestos/*chemistry/*toxicity ; Carcinogens, Environmental/*toxicity ; Humans ; Lung Neoplasms/*chemically induced/epidemiology ; Mesothelioma/*chemically induced/epidemiology ; Occupational Exposure/adverse effects ; Risk Assessment ; }, abstract = {Asbestos minerals are thin fiber type of minerals and honorably said as "the minerals of the miracle" because of their valuable natures even in the strategic field. On the other hand, the relation between asbestos exposure and diseases such as lung cancer and malignant mesothelioma was proved around 1970 by epidemiology and an animal experiment in relation to their microstructures. Here, microstructures of chrysotile asbestos, a mainstream of asbestos substances, are shown. It is also shown that in what kinds of environment people are exposed to asbestos and what kinds of biological or epidemical things happen after asbestos exposure. Many kinds of fibrous materials as the substitutes of asbestos are described in relation to their carcinogenicity.}, } @article {pmid19581213, year = {2009}, author = {Perić, I and Novak, K and Barisić, I and Mise, K and Vucković, M and Janković, S and Tocilj, J}, title = {Interobserver variations in diagnosing asbestosis according to the ILO classification.}, journal = {Arhiv za higijenu rada i toksikologiju}, volume = {60}, number = {2}, pages = {191-195}, doi = {10.2478/10004-1254-60-2009-1904}, pmid = {19581213}, issn = {1848-6312}, mesh = {Adult ; Aged ; Asbestosis/classification/*diagnostic imaging ; Female ; Humans ; Lung/*diagnostic imaging ; Male ; Middle Aged ; Observer Variation ; Radiography ; }, abstract = {Inhalation of asbestos fibres leads to asbestosis of the pleura and the lung, with possible progression to lung cancer and malignant pleural or peritoneal mesothelioma. Asbestosis remains difficult to diagnose, especially in its early stages. The most important role in its diagnosis is that of chest radiographs. The aim of this cross-sectional study was to address interobserver variations in interpreting chest radiographs in asbestos workers, which remain to be an issue, despite improvements in the International Labour Office (ILO) classification system. In our ten-year study, we investigated 318 workers occupationally exposed to asbestos, and in 210 workers with diagnosed asbestos-related changes we compared interpretations of chest radiographs according to ILO by two independent radiologists. The apparent degree of interobserver variation in classifying lung fibrosis was 26.66% for the diameter of changes and 42.2% for the profusion of the changes. In cases with diffuse pleural thickening, the interobserver variation using ILO procedures was 34.93%. This investigation raises the issue of standardisation and objectivity of interpretation of asbestosis according to the ILO classification system. This study has revealed a significant disagreement in the estimated degree of pleural and parenchymal asbestos pulmonary disease. This is why we believe high-resolution computed tomography (HRCT) should also be used as a part of international classification.}, } @article {pmid19568841, year = {2009}, author = {Murakami, S and Nishimura, Y and Maeda, M and Kumagai, N and Hayashi, H and Chen, Y and Kusaka, M and Kishimoto, T and Otsuki, T}, title = {Cytokine alteration and speculated immunological pathophysiology in silicosis and asbestos-related diseases.}, journal = {Environmental health and preventive medicine}, volume = {14}, number = {4}, pages = {216-222}, pmid = {19568841}, issn = {1342-078X}, abstract = {This review is partly composed of the presentation "Cytokine alteration and speculated immunological pathophysiology in silicosis and asbestos-related diseases" delivered during the symposium "Biological effects of fibrous and particulate substances and related areas" organized by the Study Group of Fibrous and Particulate Studies of the Japanese Society of Hygiene and held at the 78th Annual Meeting in Kumamoto, Japan. In this review, we briefly introduce the results of recent immunological analysis using the plasma of silica and asbestos-exposed patients diagnosed with silicosis, pleural plaque, or malignant mesothelioma. Thereafter, experimental background and speculation concerning the immunological pathophysiology of silica and asbestos-exposed patients are discussed.}, } @article {pmid19562730, year = {2009}, author = {Dement, J and Welch, L and Haile, E and Myers, D}, title = {Mortality among sheet metal workers participating in a medical screening program.}, journal = {American journal of industrial medicine}, volume = {52}, number = {8}, pages = {603-613}, doi = {10.1002/ajim.20725}, pmid = {19562730}, issn = {1097-0274}, support = {2 U54 OH008307-02/OH/NIOSH CDC HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Canada/epidemiology ; Child ; Child, Preschool ; Cohort Studies ; Confidence Intervals ; Construction Materials/*toxicity ; Female ; Humans ; Infant ; Lung Diseases/epidemiology/mortality ; Lung Neoplasms/epidemiology/*mortality ; Male ; *Mass Screening ; Metals/*toxicity ; Middle Aged ; Models, Statistical ; Multivariate Analysis ; Occupational Diseases/epidemiology/*mortality ; Occupational Exposure/*adverse effects ; Occupational Health/statistics & numerical data ; Proportional Hazards Models ; Risk Factors ; United States/epidemiology ; Young Adult ; }, abstract = {BACKGROUND: The Sheet Metal Occupational Health Institute Trust (SMOHIT) was formed in 1985 to examine the health hazards of the sheet metal industry in the U.S. and Canada through an asbestos disease screening program. A study of mortality patterns among screening program participants was undertaken.

METHODS: A cohort of 17,345 individuals with 20 or more years in the trade and who participated in the asbestos disease screening program were followed for vital status and causes of death between 1986 and 2004. Data from the screening program included chest X-ray results by International Labour Office (ILO) criteria and smoking history. Standardized mortality ratios (SMRs) by cause were generated using U.S. death rates and Cox proportional hazards models were used to investigate lung cancer risk relative to chest X-ray changes while controlling for smoking.

RESULTS: A significantly reduced SMR of 0.83 (95% CI = 0.80-0.85) was observed for all causes combined. Statistically significant excess mortality was observed for pleural cancers, mesothelioma, and asbestosis in the SMR analyses. Both lung cancer and COPD SMRs increased consistently and strongly with increasing ILO profusion score. In Cox models, which controlled for smoking, increased lung cancer risk was observed among workers with ILO scores of 0/1 (RR = 1.17, 95% CI = 0.89-1.54), with a strong trend for increasing lung cancer risk with increasing ILO profusion score >0/0.

CONCLUSIONS: Sheet metal workers are at increased risk for asbestos-related diseases. This study contributes to the literature demonstrating asbestos-related diseases among workers with largely indirect exposures and supports an increased lung cancer risk among workers with low ILO profusion scores.}, } @article {pmid19562727, year = {2009}, author = {Park, J and Hisanaga, N and Kim, Y}, title = {Transfer of occupational health problems from a developed to a developing country: lessons from the Japan-South Korea experience.}, journal = {American journal of industrial medicine}, volume = {52}, number = {8}, pages = {625-632}, doi = {10.1002/ajim.20723}, pmid = {19562727}, issn = {1097-0274}, mesh = {Asbestos/toxicity ; Benzidines/toxicity ; Carbon Disulfide/toxicity ; Developed Countries/*history ; Developing Countries/*history ; History, 20th Century ; History, 21st Century ; Humans ; Japan ; Manufactured Materials/*history/toxicity ; Occupational Exposure/*adverse effects ; Occupational Health/*history ; Republic of Korea ; }, abstract = {Many corporations move their manufacturing facilities or technologies from developed to developing countries. Stringent regulations have made it costly for industries to operate in developed, industrialized countries. In addition, labor costs are high in these countries, and there is increasing awareness among the general public of the health risks associated with industry. The relocation of hazardous industries to developing countries is driven by economic considerations: high unemployment, a cheaper labor force, lack of regulation, and poor enforcement of any existing regulations make certain countries attractive to business. The transfer of certain industries from Japan to Korea has also brought both documented occupational diseases and a new occupational disease caused by chemicals without established toxicities. Typical examples of documented occupational diseases are carbon disulfide poisoning in the rayon manufacturing industry, bladder cancer in the benzidine industry, and mesothelioma in the asbestos industry. A new occupational disease due to a chemical without established toxicities is 2-bromopropane poisoning. These examples suggest that counter-measures are needed to prevent the transfer of occupational health problems from a developed to a developing country. Corporate social responsibility should be emphasized, close inter-governmental collaboration is necessary and cooperation among non-governmental organizations is helpful.}, } @article {pmid19303526, year = {2009}, author = {Martínez González, C and Cruz Carmona, MJ}, title = {[Update in respiratory disease and environmental exposure: an invisible relationship].}, journal = {Archivos de bronconeumologia}, volume = {45 Suppl 1}, number = {}, pages = {21-24}, doi = {10.1016/S0300-2896(09)70267-4}, pmid = {19303526}, issn = {0300-2896}, mesh = {Environmental Exposure/*adverse effects ; Humans ; Respiratory Tract Diseases/epidemiology/*etiology ; }, abstract = {Significant contributions have been made in the past year on different aspects of occupational/environmental respiratory disease. In the case of neoplastic diseases associated with asbestos inhalation, the areas of most interest have been in the search for tumour markers, the importance of the determination of asbestos fibre deposits in biological samples, and new therapeutic schemes in malignant pleural mesothelioma. A consensus article has been published on occupational asthma, in which some clinical evidenced-based recommendations are established, directed at the diagnosis and management of work-related asthma. As regards hypersensitivity-induced pneumonitis, the clinical and evolutionary aspects of this disease have been described in a large series of 86 patients with pigeon-fancier lung. There have also been interesting studies published this year that emphasise the need to take an occupational history in patients with respiratory symptoms in order to look for a causal or synergic relationship with smoking. Finally, the results of studies have been published which were directed at elucidating the role of urban contamination, mainly caused by road traffic, in the deterioration of lung function. A recent study showed that it would be possible to achieve a significant reduction in urban mortality attributed to urban contamination by reducing the levels of PM 2.5. They conclude that more restrictive standards need to be adopted in Europe to protect the health of the population, which coincides with the proposal by the World Health Organisation.}, } @article {pmid19546821, year = {2009}, author = {Vlastos, F and Hillas, G and Vidal, P and Lacomme, S and Galateau-Sallé, F and Vollmer, E and Guzman-Costabel, J and Vignaud, JM and Martinet, N}, title = {Survey and biological insights of pemetrexed-related therapeutic improvement in mesothelioma: The Nancy Centre of Biological Resources' Mesothelioma Cohort.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {4}, number = {10}, pages = {1259-1263}, doi = {10.1097/JTO.0b013e3181aba6bd}, pmid = {19546821}, issn = {1556-1380}, mesh = {Aged ; Alleles ; Antimetabolites, Antineoplastic/*therapeutic use ; Asbestos ; Cohort Studies ; Female ; France ; Genotype ; Glutamates/*therapeutic use ; Guanine/*analogs & derivatives/therapeutic use ; Humans ; Male ; Mesothelioma/*drug therapy/genetics/pathology ; Middle Aged ; Pemetrexed ; Peritoneal Neoplasms/*drug therapy/genetics/pathology ; Polymorphism, Single Nucleotide/genetics ; Survival Rate ; Transcobalamins/genetics ; Treatment Outcome ; }, abstract = {INTRODUCTION: We report a survey of mesothelioma survival rates with insights into the survival benefit because of pemetrexed. We also studied a potential link between specific single nucleotide polymorphisms of transcobalamin II (TCII) gene and susceptibility to both asbestos and pemetrexed.

METHODS: Clinical and occupational data from 287 consecutive mesothelioma patients were collected from the north-east region of France (1989-2007). Blood or paired tumoral and normal samples were collected from the last 210 French patients to study the TCII single nucleotide polymorphisms at the codon 259 (quantitative polymerase chain reaction). Results were compared with those obtained from a group of 263 French control healthy subjects and to a group of 91 German mesothelioma patients. Patients' characteristics and genotypes results were statistically analyzed for significant correlations.

RESULTS: The mean overall patient's survival was 18.19 +/- 21.07 months. Pemetrexed increased the patients' survival by 50% (21.81 versus 16.99 months). The TCII allele Proline (Pro) was overrepresented into the mesothelioma cohort when compared with the controls (35 versus 19.77%). This also concerned German patients. The alleles Pro and Proline Arginine (ProArg) were more frequent among patients exposed to asbestos (p = 0.005, p < 0.001, respectively). The allele ProArg was associated with the longest survival while under pemetrexed (p = 0.007). No difference was found in the genotypes of patients untreated with pemetrexed.

CONCLUSIONS: Pemetrexed treatment is related to a survival increase in mesothelioma patients. The allele Pro seems overrepresented in mesothelioma patients. Those having the allele ProArg present a better outcome under pemetrexed.}, } @article {pmid19543418, year = {2009}, author = {Kim, HR}, title = {Overview of asbestos issues in Korea.}, journal = {Journal of Korean medical science}, volume = {24}, number = {3}, pages = {363-367}, pmid = {19543418}, issn = {1598-6357}, mesh = {Asbestos/*toxicity ; Asbestosis/*epidemiology/etiology/mortality ; Environmental Exposure/prevention & control ; Humans ; Korea ; Lung Neoplasms/*chemically induced ; Mesothelioma/*chemically induced/epidemiology ; }, abstract = {Asbestos is a carcinogen that causes diseases such as mesothelioma and lung cancer in humans. There was a sharp increase in the use of asbestos in Korea in the 1970s as Korea's economy developed rapidly, and asbestos was only recently banned from use. Despite the ban of its use, previously applied asbestos still causes many problems. A series of asbestos-related events that recently occurred in Korea have caused the general public to become concerned about asbestos. Therefore, it is necessary to take proper action to deal with asbestos-related events, such as mass outbreaks of mesothelioma among residents who lived near asbestos textile factories or asbestos mines. Although there have been no rapid increases in asbestos-related illnesses in Korea to date, such illnesses are expected to increase greatly due to the amount of asbestos used and long latency period. Decreasing the asbestos exposure level to levels as low as possible is the most important step in preventing asbestos-related illnesses in the next few decades. However, there is a lack of specialized facilities for the analysis of asbestos and experts to diagnose and treat asbestos-related illnesses in Korea; therefore, national-level concern and support are required.}, } @article {pmid19541802, year = {2009}, author = {Newman Taylor, A}, title = {Asbestos, lung cancer and mesothelioma in the British Journal of Industrial Medicine.}, journal = {Occupational and environmental medicine}, volume = {66}, number = {7}, pages = {426-427}, doi = {10.1136/oem.2006.026724}, pmid = {19541802}, issn = {1470-7926}, mesh = {Asbestos/*history/toxicity ; Carcinogens/*history/toxicity ; Female ; History, 20th Century ; Humans ; Lung Neoplasms/etiology/*history ; Male ; Mesothelioma/etiology/*history ; Occupational Diseases/etiology/*history ; Occupational Exposure/adverse effects/*history ; Periodicals as Topic/history ; United Kingdom ; }, } @article {pmid19523217, year = {2009}, author = {Jaurand, MC and Renier, A and Daubriac, J}, title = {Mesothelioma: Do asbestos and carbon nanotubes pose the same health risk?.}, journal = {Particle and fibre toxicology}, volume = {6}, number = {}, pages = {16}, pmid = {19523217}, issn = {1743-8977}, abstract = {Carbon nanotubes (CNTs), the product of new technology, may be used in a wide range of applications. Because they present similarities to asbestos fibres in terms of their shape and size, it is legitimate to raise the question of their safety for human health. Recent animal and cellular studies suggest that CNTs elicit tissue and cell responses similar to those observed with asbestos fibres, which increases concern about the adverse biological effects of CNTs. While asbestos fibres' mechanisms of action are not fully understood, sufficient results are available to develop hypotheses about the significant factors underlying their damaging effects. This review will summarize the current state of knowledge about the biological effects of CNTs and will discuss to what extent they present similarities to those of asbestos fibres. Finally, the characteristics of asbestos known to be associated with toxicity will be analyzed to address the possible impact of CNTs.}, } @article {pmid19522163, year = {2009}, author = {Grigoriu, BD and Grigoriu, C and Chahine, B and Gey, T and Scherpereel, A}, title = {Clinical utility of diagnostic markers for malignant pleural mesothelioma.}, journal = {Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace}, volume = {71}, number = {1}, pages = {31-38}, doi = {10.4081/monaldi.2009.374}, pmid = {19522163}, issn = {1122-0643}, mesh = {Biomarkers, Tumor/*analysis ; GPI-Linked Proteins ; Humans ; Membrane Glycoproteins/analysis ; Mesothelin ; Mesothelioma/*diagnosis/pathology ; Osteopontin/analysis ; Pleural Neoplasms/*diagnosis/pathology ; Sensitivity and Specificity ; }, abstract = {Malignant mesothelioma has a very dismal prognosis with very few patients surviving one year after diagnosis. Early multimodal treatment, however, is expected to improve the outcome. Today, there is a strong need to have disease markers which could be used for screening, diagnosing, and/or monitoring tumour response to treatment. Old markers such as hyaluronic acid, various cytokeratin fragments (CYFRA 21.1, TPA) and other cancer antigens (CA 15.3, CA 125 or CA 19.9 or CEA) are not sensitive or specific enough and cannot be used in practice. More recently new molecules, such as soluble mesothelin and osteopontin, have been proposed for diagnostic purposes. Soluble mesothelin has a good specificity but has a sub-optimal sensitivity being negative in all sarcomatoid and in up to one half of epithelioid mesothelioma. On the contrary osteopontin has an inadequate specificity. Combining different markers together does not lead to an improvement in diagnostic accuracy. Neither marker can be used for screening purposes, the main limitation being the very low incidence of the disease in the at-risk, asbestos exposed population. Mesothelin is also a promising marker for monitoring response to treatment but published data is still insufficient to make recommendations. There is still a strong need for research is this area both in order to discover new markers as well as to correct the positioning of each existing molecule (alone or in combination) is the evaluation of the patients with a mesothelioma.}, } @article {pmid19516204, year = {2009}, author = {Tsiouris, A and Kourliouros, A and Smith, EJ}, title = {Trends and challenges in treatment of malignant pleural mesothelioma.}, journal = {British journal of hospital medicine (London, England : 2005)}, volume = {70}, number = {6}, pages = {312-313}, doi = {10.12968/hmed.2009.70.6.312}, pmid = {19516204}, issn = {1750-8460}, mesh = {Asbestos/adverse effects ; Humans ; *Mesothelioma/diagnosis/etiology/therapy ; *Pleural Neoplasms/diagnosis/etiology/therapy ; }, } @article {pmid19515637, year = {2009}, author = {Chu, H and Cole, SR and Wei, Y and Ibrahim, JG}, title = {Estimation and inference for case-control studies with multiple non-gold standard exposure assessments: with an occupational health application.}, journal = {Biostatistics (Oxford, England)}, volume = {10}, number = {4}, pages = {591-602}, pmid = {19515637}, issn = {1468-4357}, support = {P30 CA016086/CA/NCI NIH HHS/United States ; }, mesh = {Asbestos/administration & dosage/adverse effects ; Biostatistics/*methods ; Case-Control Studies ; Confidence Intervals ; Data Collection ; Humans ; Likelihood Functions ; Mesothelioma/etiology ; Models, Statistical ; Occupational Exposure/standards/*statistics & numerical data ; Occupational Health/statistics & numerical data ; United States ; }, abstract = {In occupational case-control studies, work-related exposure assessments are often fallible measures of the true underlying exposure. In lieu of a gold standard, often more than 2 imperfect measurements (e.g. triads) are used to assess exposure. While methods exist to assess the diagnostic accuracy in the absence of a gold standard, these methods are infrequently used to correct for measurement error in exposure-disease associations in occupational case-control studies. Here, we present a likelihood-based approach that (a) provides evidence regarding whether the misclassification of tests is differential or nondifferential; (b) provides evidence whether the misclassification of tests is independent or dependent conditional on latent exposure status, and (c) estimates the measurement error-corrected exposure-disease association. These approaches use information from all imperfect assessments simultaneously in a unified manner, which in turn can provide a more accurate estimate of exposure-disease association than that based on individual assessments. The performance of this method is investigated through simulation studies and applied to the National Occupational Hazard Survey, a case-control study assessing the association between asbestos exposure and mesothelioma.}, } @article {pmid19515047, year = {2009}, author = {Abban, C and Viglione, M}, title = {Peritoneal mesothelioma presenting as a skin nodule.}, journal = {Journal of cutaneous pathology}, volume = {36}, number = {6}, pages = {675-679}, doi = {10.1111/j.1600-0560.2008.01094.x}, pmid = {19515047}, issn = {1600-0560}, mesh = {Aged ; Appendectomy ; Asbestos/adverse effects ; Cicatrix/pathology ; Humans ; Immunohistochemistry ; Male ; Mesothelioma/etiology/metabolism/*secondary ; Occupational Exposure/adverse effects ; Peritoneal Neoplasms/etiology/metabolism/*pathology ; Skin Neoplasms/etiology/metabolism/*secondary ; }, abstract = {Mesothelioma is a malignancy of the pleura, pericardium and peritoneum that is rarely seen in cutaneous biopsies. We present a case of a 75-year-old man with significant occupational exposure to asbestos who developed peritoneal mesothelioma that presented as a skin nodule in an old appendectomy scar. The patient presented with a complaint of increased hardness along his appendectomy scar. Physical examination revealed an anterior abdominal wall mass overlying the appendectomy scar, which was subsequently biopsied. Histologic examination of the abdominal wall mass revealed an infiltrating epithelioid and papillary neoplasm within the dermis and subcutaneous tissue. Immunohistochemical stains showed immunoreactivity for cytokeratin (CK) 7, CK 5/6, calretinin and vimentin. CK 20, monoclonal carcinoembryonic antigen, prostate-specific antigen and prostate-specific acid phosphatase were negative. The profile supported the diagnosis of mesothelioma. Cutaneous presentation of mesothelioma is rare but should be considered in the differential diagnosis of patients with significant asbestos exposure.}, } @article {pmid19514493, year = {2009}, author = {Hasegawa, Y and Nagayasu, F and Moriyama, A and Uejima, H and Yoon, HE}, title = {[Twenty-one patients of malignant pleural mesothelioma in the Senshu district].}, journal = {Nihon Kokyuki Gakkai zasshi = the journal of the Japanese Respiratory Society}, volume = {47}, number = {5}, pages = {347-354}, pmid = {19514493}, issn = {1343-3490}, mesh = {Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Drug Therapy ; Environmental Exposure/adverse effects ; Female ; Humans ; Japan/epidemiology ; Male ; Mesothelioma/diagnosis/*etiology/mortality/*therapy ; Middle Aged ; Occupational Exposure/*adverse effects ; Pleura/surgery ; Pleural Neoplasms/*diagnosis/etiology/mortality/*therapy ; Pneumonectomy ; Radiotherapy ; Retrospective Studies ; Survival Rate ; }, abstract = {Twenty-one patients (15 men, 6 women, median age 67) were given a diagnosis of malignant pleural mesothelioma between March 1998 and December 2007 in our hospital. There was apparent occupational exposure of asbestos in 11 patients and suspicion of asbestos exposure in 5. Mean period recuired for diagnosis was 60 days with VATS and percutaneous needle biopsy. Eight patients underwent pleuropneumonectomy. Their median survival was 14.4 months, and the 2-year survival rate was approximately 30%. Seven other patients received chemotherapy, another patient underwent palliative radiotherapy and the remaining 5 patients received best supportive care. One patient had long survived (41.6 months) with gemcitabine-based chemotherapy. In the Senshu district, in the southern part of Osaka, there have been many asbestos spinning mills, so environmental exposure might occur. We should try to diagnose malignant mesothelioma for patients with pleural effusion even if they apparently do not have a history of asbestos exposure.}, } @article {pmid19502386, year = {2010}, author = {Busacca, S and Germano, S and De Cecco, L and Rinaldi, M and Comoglio, F and Favero, F and Murer, B and Mutti, L and Pierotti, M and Gaudino, G}, title = {MicroRNA signature of malignant mesothelioma with potential diagnostic and prognostic implications.}, journal = {American journal of respiratory cell and molecular biology}, volume = {42}, number = {3}, pages = {312-319}, doi = {10.1165/rcmb.2009-0060OC}, pmid = {19502386}, issn = {1535-4989}, mesh = {Aged ; Biomarkers, Tumor/genetics/metabolism ; Cell Line, Tumor ; Female ; *Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Male ; Mesothelioma/*diagnosis/*genetics/pathology ; MicroRNAs/*genetics/metabolism ; Middle Aged ; Prognosis ; Survival Analysis ; }, abstract = {MicroRNAs (miRNAs) post-transcriptionally regulate the expression of target genes, and may behave as oncogenes or tumor suppressors. Human malignant mesothelioma is an asbestos-related cancer, with poor prognosis and low median survival. Here we report, for the first time, a cross-evaluation of miRNA expression in mesothelioma (MPP-89, REN) and human mesothelial cells (HMC-telomerase reverse transcriptase). Microarray profiling, confirmed by real-time quantitative RT-PCR, revealed a differential expression of miRNAs between mesothelioma and mesothelial cells. In addition, a computational analysis combining miRNA and gene expression profiles allowed the accurate prediction of genes potentially targeted by dysregulated miRNAs. Several predicted genes belong to terms of Gene Ontology (GO) that are associated with the development and progression of mesothelioma. This suggests that miRNAs may be key players in mesothelioma oncogenesis. We further investigated miRNA expression on a panel of 24 mesothelioma specimens, representative of the three histotypes (epithelioid, biphasic, and sarcomatoid), by quantitative RT-PCR. The expression of miR-17-5p, miR-21, miR-29a, miR-30c, miR-30e-5p, miR-106a, and miR-143 was significantly associated with the histopathological subtypes. Notably, the reduced expression of two miRNAs (miR-17-5p and miR-30c) correlated with better survival of patients with sarcomatoid subtype. Our preliminary analysis points at miRNAs as potential diagnostic and prognostic markers of mesothelioma, and suggests novel tools for the therapy of this malignancy.}, } @article {pmid19501947, year = {2009}, author = {Tarrés, J and Abós-Herràndiz, R and Albertí, C and Martínez-Artés, X and Rosell-Murphy, M and García-Allas, I and Krier, I and Castro, E and Cantarell, G and Gallego, M and Orriols, R}, title = {[Asbestos-related diseases in a population near a fibrous cement factory].}, journal = {Archivos de bronconeumologia}, volume = {45}, number = {9}, pages = {429-434}, doi = {10.1016/j.arbres.2009.04.007}, pmid = {19501947}, issn = {1579-2129}, mesh = {Aged ; Asbestos/*adverse effects ; Asbestosis/*epidemiology/etiology ; *Construction Materials ; *Environmental Exposure ; Female ; Humans ; Incidence ; Lung Neoplasms/*epidemiology/etiology ; Male ; Medical Records ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Exposure ; Peritoneal Neoplasms/*epidemiology/etiology ; Pleural Effusion/epidemiology/etiology ; Pleural Neoplasms/*epidemiology/etiology ; Pleurisy/epidemiology/etiology ; Prevalence ; Pulmonary Atelectasis/epidemiology/etiology ; Pulmonary Disease, Chronic Obstructive/epidemiology/etiology ; Retrospective Studies ; Risk ; Spain ; Time Factors ; }, abstract = {BACKGROUND AND OBJECTIVE: The first fibrous cement factory in Spain was set up in Cerdanyola, Barcelona, in 1907 and was a source of pollution there until it was closed in 1997. The aim of this study was to determine the clinical and epidemiologic characteristics of the population with by asbestos-related diseases who had worked in the factory and/or lived in the vicinity.

MATERIAL AND METHODS: We retrospectively collected information available on patients with asbestos-related diseases who at the time of diagnosis had resided in the area near the fibrous cement factory. Information was obtained from the medical records of the primary care centers of the 12 surrounding towns and the sole referral hospital in the area for cases diagnosed between January 1, 1970 and December 31, 2006.

RESULTS: In the 559 patients diagnosed, 1107 cases of asbestos-related diseases were identified. Between 2000 and 2006, the average annual incidence was 9.5 cases per 100,000 inhabitants for the entire study area and 35.5 cases per 100,000 for the area nearest the factory. The prevalence of asbestos-related diseases as of December 31, 2006 was 91 cases per 100,000 inhabitants in the entire study area and 353.4 cases per 100,000 in the area nearest the factory. Of the 1107 asbestos-related disease cases identified, 86.5% were benign and 8.4% pleural mesothelioma.

CONCLUSIONS: The factory introduced an important area-wide risk factor for asbestos-related diseases for both workers and for the nearby population. The number of cases of asbestos-related diseases detected annually showed an upward trend. The incidence was extremely high in the period studied.}, } @article {pmid19499669, year = {2009}, author = {Beznea, A and Truş, CT and Chicoş, SC and Chebac, GR and Ceauşu, M}, title = {[Malignant peritoneal mesothelioma].}, journal = {Chirurgia (Bucharest, Romania : 1990)}, volume = {104}, number = {2}, pages = {227-230}, pmid = {19499669}, issn = {1221-9118}, mesh = {Abdomen, Acute/etiology/surgery ; Biopsy ; Hemoperitoneum/etiology/surgery ; Humans ; Male ; Mesothelioma/complications/*diagnosis/diagnostic imaging/pathology/surgery ; Middle Aged ; Neoplasm Staging ; Peritoneal Neoplasms/complications/*diagnosis/diagnostic imaging/pathology/surgery ; Tomography, X-Ray Computed ; Treatment Outcome ; }, abstract = {This work presents the case of a hemorrhagic, necrotized peritoneal malignant mesothelioma in a 46-year old man, discovered during the emergency surgery, performed for an acute surgical abdomen/hemoperitoneum. Mesotheliomas are rare neoplasms of the pleura, peritoneum or pericardium, which are frequently associated with exposure to asbestos. The paraclinical investigations (echography) were not able to specify the diagnosis before the operation. The surgical intervention--tumorectomy, electrocoagulation, hemostasis with Gelaspon sponges-- had favourable results.}, } @article {pmid19496488, year = {2009}, author = {Hessel, PA}, title = {Inaccuracies in article on mesothelioma in brake workers.}, journal = {International journal of occupational and environmental health}, volume = {15}, number = {2}, pages = {232-4; author reply 234-8}, doi = {10.1179/oeh.2009.15.2.232}, pmid = {19496488}, issn = {1077-3525}, mesh = {Air Pollutants, Occupational/adverse effects ; Asbestos/*adverse effects ; Automobiles ; Data Interpretation, Statistical ; Humans ; Liability, Legal ; Lung Neoplasms/*chemically induced ; Mesothelioma/*chemically induced ; Occupational Exposure/*adverse effects/legislation & jurisprudence ; Scientific Misconduct ; }, } @article {pmid19496487, year = {2009}, author = {Egilman, D}, title = {Fiber types, asbestos potency, and environmental causation: a peer review of published work and legal and regulatory scientific testimony.}, journal = {International journal of occupational and environmental health}, volume = {15}, number = {2}, pages = {202-228}, doi = {10.1179/oeh.2009.15.2.202}, pmid = {19496487}, issn = {1077-3525}, mesh = {Adult ; Aged ; Asbestos/*adverse effects/analysis ; Bias ; Environmental Exposure/*adverse effects/analysis ; Environmental Monitoring/methods ; Epidemiological Monitoring ; Female ; Humans ; Lung Neoplasms/chemically induced/*epidemiology ; Mesothelioma/chemically induced/*epidemiology ; Middle Aged ; *Peer Review ; Public Policy ; SEER Program ; }, abstract = {Scientific evidence and analysis offered in litigation and public policy testimony have an important role in occupational and environmental health, but are not subject to peer review. Critique and commentary, attempts at reproduction of results, and review of data offered in such testimony is essential. Peer review of such testimony should become part of the domain of medical and scientific journals. This paper is an effort to peer review the use of certain scientific methods in tort litigation and in testimony before regulatory agencies. In this issue of IJOEH, Azuma et al. show that background asbestos exposures can be considered to have caused mesothelioma. In contrast, epidemiologic studies and testimony by Teta et al. and Price and Ware, and pathologic studies and testimony by Roggli and others, claim that background exposures are benign. These are fatally flawed because of methodological and analytic errors.}, } @article {pmid19496483, year = {2009}, author = {Azuma, K and Uchiyama, I and Chiba, Y and Okumura, J}, title = {Mesothelioma risk and environmental exposure to asbestos: past and future trends in Japan.}, journal = {International journal of occupational and environmental health}, volume = {15}, number = {2}, pages = {166-172}, doi = {10.1179/oeh.2009.15.2.166}, pmid = {19496483}, issn = {1077-3525}, mesh = {Air Pollutants/*adverse effects ; Asbestos/*adverse effects ; Environmental Exposure/*adverse effects/analysis ; *Environmental Monitoring ; Epidemiological Monitoring ; Forecasting ; Humans ; Incidence ; Japan/epidemiology ; Lung Neoplasms/chemically induced/mortality ; Mesothelioma/*chemically induced/mortality ; Models, Biological ; Risk Factors ; }, abstract = {Although asbestos has been widely distributed in the environment, health risks due to general environmental exposure to asbestos have not been estimated. Future mesothelioma risk from environmental exposure to asbestos in Japan was estimated by comparing historical exposure data and mortality attributed to environmental exposure. We developed an equation to estimate environmentally-attributable mesothelioma based on the US Environmental Protection Agency's model for occupational mesothelioma mortality. Based on our calculations, mesothelioma risks per year of exposure will reach peak levels in 2033 and range from 4.8 x 10(-6) to 1.1 x 10(-5). The number of deaths is estimated to range from 542-1276 in 2033. The cumulative number of deaths will reach around 17,000-37,000 in the years 1970-2070. Our estimation of risk approximately corresponded to observed risks. Past and predicted future disease suggest the need for social and medical support in these areas.}, } @article {pmid19487281, year = {2009}, author = {Pinton, G and Brunelli, E and Murer, B and Puntoni, R and Puntoni, M and Fennell, DA and Gaudino, G and Mutti, L and Moro, L}, title = {Estrogen receptor-beta affects the prognosis of human malignant mesothelioma.}, journal = {Cancer research}, volume = {69}, number = {11}, pages = {4598-4604}, doi = {10.1158/0008-5472.CAN-08-4523}, pmid = {19487281}, issn = {1538-7445}, mesh = {Adult ; Aged ; Aged, 80 and over ; Case-Control Studies ; Cell Cycle/genetics ; Disease Progression ; Estrogen Receptor beta/genetics/*metabolism/*physiology ; Female ; Humans ; Male ; Mesothelioma/*diagnosis/metabolism/mortality ; Middle Aged ; Pleural Neoplasms/*diagnosis/metabolism/mortality ; Prognosis ; Survival Analysis ; Tumor Cells, Cultured ; }, abstract = {Malignant pleural mesothelioma is an asbestos-related neoplasm with poor prognosis, refractory to current therapies, the incidence of which is expected to increase in the next decades. Female gender was identified as a positive prognostic factor among other clinical and biological prognostic markers for malignant mesothelioma, yet a role of estrogen receptors (ERs) has not been studied. Our goal was to investigate ERs expression in malignant mesothelioma and to assess whether their expression correlates with prognosis. Immunohistochemical analysis revealed intense nuclear ERbeta staining in normal pleura that was reduced in tumor tissues. Conversely, neither tumors nor normal pleura stained positive for ERalpha. Multivariate analysis of 78 malignant mesothelioma patients with pathologic stage, histologic type, therapy, sex, and age at diagnosis indicated that ERbeta expression is an independent prognostic factor of better survival. Moreover, studies in vitro confirmed that treatment with 17beta-estradiol led to an ERbeta-mediated inhibition of malignant mesothelioma cell proliferation as well as p21(CIP1) and p27(KIP1) up-regulation. Consistently cell growth was suppressed by ERbeta overexpression, causing a G(2)-M-phase cell cycle arrest, paralleled by cyclin B1 and survivin down-regulation. Our data support the notion that ERbeta acting as a tumor suppressor is of high potential relevance to prediction of disease progression and to therapeutic response of malignant mesothelioma patients.}, } @article {pmid19485980, year = {2009}, author = {Clin, B and Morlais, F and Dubois, B and Guizard, AV and Desoubeaux, N and Marquignon, MF and Raffaelli, C and Paris, C and Galateau-Salle, F and Launoy, G and Letourneux, M}, title = {Occupational asbestos exposure and digestive cancers - a cohort study.}, journal = {Alimentary pharmacology & therapeutics}, volume = {30}, number = {4}, pages = {364-374}, doi = {10.1111/j.1365-2036.2009.04050.x}, pmid = {19485980}, issn = {1365-2036}, mesh = {Asbestos/*adverse effects ; Cohort Studies ; Digestive System Neoplasms/epidemiology/*etiology/mortality ; Female ; France/epidemiology ; Humans ; Male ; Morbidity ; Occupational Exposure/*adverse effects ; Retrospective Studies ; Statistics as Topic ; Time Factors ; }, abstract = {BACKGROUND: Although the role of asbestos in the genesis of mesothelioma and primary bronchopulmonary cancers has been established, results from studies focusing on the relationship between occupational exposure to asbestos and digestive cancer remain contradictory.

AIM: To determine whether occupational asbestos exposure increases the incidence of digestive cancers.

METHODS: Our study was a retrospective morbidity study based on 2024 subjects occupationally exposed to asbestos. The incidence of digestive cancer was calculated from 1st January 1978 to 31st December 2004 and compared with levels among the local general population using Standardized Incidence Ratios. Asbestos exposure was assessed using the company's job exposure matrix.

RESULTS: Eighty-five cases of digestive cancer were observed within our cohort, for an expected number of 66.90 (SIR = 1.27 [1.01; 1.57]). A significantly elevated incidence, particularly notable among women, was observed for peritoneal mesothelioma, independently of exposure levels. A significantly elevated incidence was also noted among men for cancer of small intestine and oesophagus, for cumulative exposure indexes for asbestos above 80 fibres/mL x years. A significantly elevated incidence of cancer of the small intestine was also observed among men having been exposed to asbestos for periods in excess of 25 years and for mean exposure levels in excess of 4 fibres/mL.

CONCLUSIONS: This study suggests the existence of a relationship between exposure to asbestos and cancer of the small intestine and of the oesophagus in men.}, } @article {pmid19484745, year = {2009}, author = {Cree, MW and Lalji, M and Jiang, B and Carriere, KC}, title = {Under-reporting of compensable mesothelioma in Alberta.}, journal = {American journal of industrial medicine}, volume = {52}, number = {7}, pages = {526-533}, doi = {10.1002/ajim.20705}, pmid = {19484745}, issn = {1097-0274}, mesh = {Aged ; Alberta ; Asbestosis/diagnosis/epidemiology/pathology ; Cross-Sectional Studies ; Disease Notification/legislation & jurisprudence ; Eligibility Determination/legislation & jurisprudence/statistics & numerical data ; Female ; Humans ; Incidence ; Insurance Claim Reporting/legislation & jurisprudence/*statistics & numerical data ; Insurance Claim Review ; Male ; Mesothelioma/diagnosis/*epidemiology/pathology ; Middle Aged ; Peritoneal Neoplasms/diagnosis/*epidemiology/pathology ; Pleural Neoplasms/diagnosis/*epidemiology/pathology ; Registries ; Workers' Compensation/legislation & jurisprudence/*statistics & numerical data ; }, abstract = {BACKGROUND: When combined with a history of occupational asbestos exposure, mesothelioma is often presumed work-related. In Canada, workers diagnosed with mesothelioma caused by occupational asbestos exposure are often eligible for compensation under provincial workers' compensation boards. Although occupational asbestos exposure causes the majority of mesothelioma, Canadian research suggests less than half of workers actually apply for compensation. Alberta's mandatory reporting requirements may produce higher filing rates but this is currently unknown. This study evaluates Alberta's mesothelioma filing and compensation rates.

METHODS: Demographic information on all mesothelioma patients diagnosed between 1980 and 2004 were extracted from the Alberta Cancer Board's Cancer Registry and linked to Workers' Compensation Board of Alberta claims data.

RESULTS: Alberta recorded a total of 568 histologically confirmed mesothelioma cases between 1980 and 2004. Forty-two percent of cases filed a claim; 83% of filed claims were accepted for compensation.

CONCLUSIONS: Patient under-reporting of compensable mesothelioma is a problem and raises larger questions regarding under-reporting of other asbestos-related cancers in Alberta. Strategies should focus on increasing filing rates where appropriate.}, } @article {pmid19469424, year = {2009}, author = {Madkour, MT and El Bokhary, MS and Awad Allah, HI and Awad, AA and Mahmoud, HF}, title = {Environmental exposure to asbestos and the exposure-response relationship with mesothelioma.}, journal = {Eastern Mediterranean health journal = La revue de sante de la Mediterranee orientale = al-Majallah al-sihhiyah li-sharq al-mutawassit}, volume = {15}, number = {1}, pages = {25-38}, pmid = {19469424}, issn = {1020-3397}, mesh = {Adult ; Aged ; *Air Pollutants/adverse effects/analysis ; *Asbestos/adverse effects/analysis ; Biopsy ; Case-Control Studies ; Egypt/epidemiology ; *Environmental Exposure/adverse effects/analysis ; Environmental Monitoring/methods ; Epidemiological Monitoring ; Female ; Humans ; Inhalation Exposure/adverse effects/analysis ; Male ; Mesothelioma/diagnosis/*epidemiology/etiology ; Middle Aged ; Occupational Exposure/adverse effects/analysis ; Pleural Neoplasms/diagnosis/*epidemiology/etiology ; Prevalence ; Residence Characteristics ; Risk Factors ; Sex Distribution ; Statistics, Nonparametric ; Urban Health/statistics & numerical data ; }, abstract = {An epidemiological and environmental study was carried out in Shubra El-Kheima city, greater Cairo, of the exposure-response relationship between asbestos and malignant pleural mesothelioma. Radiological screening was done for 487 people occupationally exposed to asbestos, 2913 environmentally exposed to asbestos and a control group of 979 with no history of exposure. Pleural biopsy was done for suspicious cases. The airborne asbestos fibre concentrations were determined in all areas. There were 88 cases of mesothelioma diagnosed, 87 in the exposed group. The risk of mesothelioma was higher in the environmentally exposed group than other groups, and higher in females than males. The prevalence of mesothelioma increased with increased cumulative exposure to asbestos.}, } @article {pmid19468116, year = {2009}, author = {Collier, R}, title = {Asbestos panel chair mystified by secrecy surrounding report.}, journal = {CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne}, volume = {180}, number = {11}, pages = {1100-1101}, doi = {10.1503/cmaj.090728}, pmid = {19468116}, issn = {1488-2329}, mesh = {Asbestos, Serpentine/*adverse effects ; Canada/epidemiology ; Consensus Development Conferences as Topic ; Expert Testimony ; Humans ; *Lung Neoplasms/chemically induced/epidemiology/prevention & control ; *Mesothelioma/chemically induced/epidemiology/prevention & control ; Mining/*legislation & jurisprudence ; Morbidity/trends ; Occupational Exposure/*adverse effects ; *Politics ; Risk Assessment ; }, } @article {pmid19461615, year = {2009}, author = {Fry, C}, title = {An investigation into asbestos related disease in the dental industry.}, journal = {British dental journal}, volume = {206}, number = {10}, pages = {515-516}, doi = {10.1038/sj.bdj.2009.413}, pmid = {19461615}, issn = {1476-5373}, mesh = {Asbestos/*adverse effects ; Dentists ; Humans ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; Occupational Exposure/*adverse effects ; Periodontal Dressings/adverse effects ; }, abstract = {This article discusses the dangers of the asbestos-based disease mesothelioma and the possible origins of this form of cancer in dental professionals. The potential for an increase in diagnosed cases of mesothelioma among dentists and technicians in future is highlighted.}, } @article {pmid19461608, year = {2009}, author = {}, title = {Asbestos related disease investigated.}, journal = {British dental journal}, volume = {206}, number = {10}, pages = {512}, doi = {10.1038/sj.bdj.2009.444}, pmid = {19461608}, issn = {1476-5373}, mesh = {Asbestos/*adverse effects ; *Dentists ; Humans ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; Occupational Exposure/*adverse effects ; }, } @article {pmid19461404, year = {2009}, author = {Flood, TA and Sekhon, HS and Seely, JM and Shamji, FM and Gomes, MM}, title = {Spontaneous pneumothorax and lung carcinoma: should one consider synchronous malignant pleural mesothelioma?.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {4}, number = {6}, pages = {770-772}, doi = {10.1097/JTO.0b013e3181a52c3f}, pmid = {19461404}, issn = {1556-1380}, mesh = {Aged ; Carcinoma, Non-Small-Cell Lung/*diagnosis/metabolism ; Humans ; Lung Neoplasms/*diagnosis/metabolism ; Male ; Mesothelioma/*diagnosis/metabolism ; Neoplasms, Multiple Primary/*diagnosis/metabolism ; Pleural Neoplasms/*diagnosis/metabolism ; Pneumothorax/*diagnosis/metabolism ; Tomography, X-Ray Computed ; }, abstract = {We describe the clinical and pathologic findings of a 68-year-old smoker with previous asbestos exposure who presented with spontaneous hydropneumothorax and was diagnosed with synchronous undifferentiated lung carcinoma and incidental malignant pleural mesothelioma. The synchronous occurrence of these two neoplasms is an extremely rare event with fewer than 20 reported cases in the English literature. The accurate diagnosis of synchronous tumors can be extremely challenging and the identification of a concomitant mesothelioma in our case was not made until an extensive immunohistochemical analysis was done on the resection specimen. Spontaneous pneumothorax occurs much more commonly in patients with malignant mesothelioma than with primary lung carcinomas. Consequently, although synchronous pleural mesotheliomas and lung carcinomas are infrequent, this diagnosis should be considered when a patient with a lung mass and a history of asbestos exposure presents with spontaneous pneumothorax and pleural thickening on imaging. Identification of synchronous tumors is of critical importance for determining the patient's stage and management and can have significant medicolegal implications should the patient seek compensation.}, } @article {pmid19460788, year = {2009}, author = {Aceto, N and Bertino, P and Barbone, D and Tassi, G and Manzo, L and Porta, C and Mutti, L and Gaudino, G}, title = {Taurolidine and oxidative stress: a rationale for local treatment of mesothelioma.}, journal = {The European respiratory journal}, volume = {34}, number = {6}, pages = {1399-1407}, doi = {10.1183/09031936.00102308}, pmid = {19460788}, issn = {1399-3003}, mesh = {Antineoplastic Agents/*therapeutic use ; Apoptosis ; Cell Death ; Cell Line, Tumor ; Cells, Cultured ; DNA/metabolism ; Fibroblasts/metabolism ; Humans ; In Situ Nick-End Labeling ; Lung Neoplasms/*drug therapy/*pathology ; Mesothelioma/*drug therapy/*pathology ; *Oxidative Stress ; Proto-Oncogene Proteins c-akt/metabolism ; Taurine/*analogs & derivatives/therapeutic use ; Thiadiazines/*therapeutic use ; Time Factors ; }, abstract = {Malignant mesothelioma is an asbestos-related, aggressive tumour, resistant to most anticancer therapies. Akt is a key mediator of mesothelioma cell survival and chemoresistance. This study aimed to clarify the mechanism by which taurolidine (TN), a known synthetic compound with antimicrobial and antineoplastic properties, leads to mesothelioma cell death. Apoptosis was studied by annexin V binding, cell cycle analysis, caspase-8 activation, poly(ADP-ribose) polymerase (PARP) cleavage and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling (TUNEL). Oxidative stress was measured by nitrite production and DNA oxidative damage. Protein expression and phosphorylation were evaluated by immunoprecipitation and immunoblotting. TN induces cell death of mesothelioma cells, but not of non-neoplastic human mesothelial cells. After TN treatment of mesothelioma cells, Akt but not extracellular signal-regulated kinase (Erk) 1/2 activity is inhibited a in time- and dose-dependent manner. Protein phosphatase (PP)1alpha and PP2A are activated several hours after drug addition. Apoptosis induced by TN is driven by oxidative stress and cell exposure to sulfydryl donors, such as glutathione monoethylester and l-N-acetylcysteine, significantly reduced pro-apoptotic effects and Akt inhibition. Conversely, expression of constitutively activated Akt did not affect cytoxicity elicited by TN, which retained its ability to inhibit the kinase. TN induces mesothelioma cell death via oxidative stress, accompanied by inhibition of Akt signalling. This provides a promising molecular rationale for TN as local treatment of malignant mesothelioma.}, } @article {pmid19456032, year = {2009}, author = {Montjoy, C and Parker, J and Petsonk, L and Luis, T and Fallon, K}, title = {Mesothelioma review.}, journal = {The West Virginia medical journal}, volume = {105}, number = {3}, pages = {13-16}, pmid = {19456032}, issn = {0043-3284}, mesh = {Adult ; Age Factors ; Asbestos/toxicity ; Female ; Humans ; Lung Neoplasms/epidemiology/*pathology/therapy ; Male ; Mesothelioma/epidemiology/*pathology/therapy ; Neoplasm Metastasis ; Prognosis ; Risk Factors ; Sex Distribution ; }, abstract = {Malignant mesothelioma (MME) is an aggressive tumor of serosal surfaces resistant to current treatment options. MME is typically diagnosed in middle aged males exposed to asbestos in the workplace. However, MME is occasionally diagnosed at an earlier age without an obvious source of exposure. MME typically carries an average survival rate of six to thirteen months. A new treatment option, the trimodality approach, has recently been proclaimed as superior to standard treatment. Therefore, a case of a 38-year-old-female diagnosed with MME is reported to review its epidemiology, pathogenesis, clinical presentation, diagnostic modalities and most current treatment options.}, } @article {pmid19444627, year = {2009}, author = {Goodman, JE and Nascarella, MA and Valberg, PA}, title = {Ionizing radiation: a risk factor for mesothelioma.}, journal = {Cancer causes & control : CCC}, volume = {20}, number = {8}, pages = {1237-1254}, doi = {10.1007/s10552-009-9357-4}, pmid = {19444627}, issn = {1573-7225}, mesh = {Humans ; Lung Neoplasms/epidemiology/*etiology ; Mesothelioma/epidemiology/*etiology ; Neoplasms/radiotherapy ; *Neoplasms, Radiation-Induced/epidemiology ; Radiation, Ionizing ; Radiotherapy/adverse effects ; Risk Factors ; Thorium Dioxide/adverse effects ; }, abstract = {In the majority of mesothelioma cases worldwide, asbestos is a likely causal factor, but several alternative factors, such as ionizing radiation, have been recognized. We reviewed ionizing-radiation evidence from epidemiology studies of (1) patients exposed to the diagnostic X-ray contrast medium "Thorotrast," (2) patients undergoing radiation therapy (i.e., to treat cancer), and (3) atomic energy workers chronically exposed to lower levels of radiation. The results from these populations are also supported by case reports of mesothelioma following therapeutic radiation. Statistically significant associations were found in many, but not all, epidemiology studies (particularly those of Thorotrast- and radiation-treated patients). Given the low mesothelioma rate in the general population, the consistently increased risk among these radiation-exposed individuals is noteworthy. Many studies were limited by the lack of a uniform manner in which mesothelioma was reported prior to introduction of a uniform classification system (ICD-10). Future studies that rely on ICD-10 should have greater power to detect an association. While the evidence falls short of a definitive causal link, considering studies in which statistical significance was achieved, the case reports, and the plausible mode of action, we conclude that the evidence is supportive of a causal link between ionizing radiation exposure and mesothelioma risk.}, } @article {pmid19443527, year = {2009}, author = {Tabata, C and Tabata, R and Hirayama, N and Yasumitsu, A and Yamada, S and Murakami, A and Iida, S and Tamura, K and Terada, T and Kuribayashi, K and Fukuoka, K and Nakano, T}, title = {All-trans-retinoic acid inhibits tumour growth of malignant pleural mesothelioma in mice.}, journal = {The European respiratory journal}, volume = {34}, number = {5}, pages = {1159-1167}, doi = {10.1183/09031936.00195708}, pmid = {19443527}, issn = {1399-3003}, mesh = {Animals ; Asbestos ; Becaplermin ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Female ; Interleukin-6/metabolism ; Mesothelioma/*drug therapy ; Mice ; Mice, SCID ; Neoplasm Transplantation ; Platelet-Derived Growth Factor/metabolism ; Pleural Neoplasms/*drug therapy ; Proto-Oncogene Proteins c-sis ; RNA, Messenger/metabolism ; Receptor, Platelet-Derived Growth Factor beta/metabolism ; Transforming Growth Factor beta1/metabolism ; Tretinoin/*pharmacology ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive malignant tumour of mesothelial origin associated with asbestos exposure. Because MPM has limited response to conventional chemotherapy and radiotherapy, the prognosis is very poor. Several researchers have reported that cytokines such as interleukin (IL)-6 play an important role in the growth of MPM. Previously, it was reported that all-trans-retinoic acid (ATRA) inhibited the production and function of IL-6 and transforming growth factor (TGF)-beta1 in experiments using lung fibroblasts. We investigated whether ATRA had an inhibitory effect on the cell growth of MPM, the origin of which was mesenchymal cells similar to lung fibroblasts, using a subcutaneous xenograft mouse model. We estimated the tumour growth and performed quantitative measurements of IL-6, TGF-beta1 and platelet-derived growth factor (PDGF) receptor (PDGFR)-beta mRNA levels both of cultured MPM cells and cells grown in mice with or without the administration of ATRA. ATRA significantly inhibited MPM tumour growth. In vitro studies disclosed that the administration of ATRA reduced 1) mRNA levels of TGF-beta1, TGF-beta1 receptors and PDGFR-beta, and 2) TGF-beta1-dependent proliferation and PDGF-BB-dependent migration of MPM cells. These data may provide a rationale to explore the clinical use of ATRA for the treatment of MPM.}, } @article {pmid19435981, year = {2009}, author = {Turci, F and Tomatis, M and Compagnoni, R and Fubini, B}, title = {Role of associated mineral fibres in chrysotile asbestos health effects: the case of balangeroite.}, journal = {The Annals of occupational hygiene}, volume = {53}, number = {5}, pages = {491-497}, doi = {10.1093/annhyg/mep028}, pmid = {19435981}, issn = {1475-3162}, mesh = {Asbestos, Amphibole ; Asbestos, Serpentine/*toxicity ; Carcinogens ; Confounding Factors, Epidemiologic ; Humans ; Italy ; Microscopy, Electron, Transmission ; Mineral Fibers/*toxicity ; *Mining ; Occupational Exposure ; Spectrophotometry, Atomic ; Toxicity Tests/*methods ; }, abstract = {OBJECTIVES: To evaluate the biodurability of balangeroite, present as contaminant of chrysotile asbestos in the Balangero mine, in order to have indication whether it might have been a confounding factor in the association of the mesothelioma cases reported among mine workers and employees.

METHODS: The modifications taking place following incubation of the fibres in simulated phagolysosomal fluids have been measured on balangeroite, on one pure chrysotile sample (Val Malenco), on one chrysotile from Balangero with some associated balangeroite, and on two tremolite samples.

RESULTS: The incubation modifies both chrysotile and balangeroite with substantial release in the medium of the metal ions which occupy the octahedral site in the mineral structure of the fibre while tremolite is virtually unaffected.

CONCLUSIONS: Considering the profound differences between the structure of balangeroite and amphiboles, previous results and observations on the poor ecopersistence of balangeroite, and the present data, we conclude that balangeroite traces may contribute to the overall toxicity of the airborne fibres in Balangero, but may not be compared to tremolite nor considered the sole responsible for the excess of mesothelioma found in Balangero.}, } @article {pmid19435979, year = {2009}, author = {Ogden, TL}, title = {Canadian chrysotile report released--at last.}, journal = {The Annals of occupational hygiene}, volume = {53}, number = {4}, pages = {307-309}, doi = {10.1093/annhyg/mep031}, pmid = {19435979}, issn = {1475-3162}, mesh = {Asbestos, Serpentine/*toxicity ; Canada ; Consensus ; Humans ; Inhalation Exposure ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Meta-Analysis as Topic ; Occupational Exposure ; *Occupational Health ; Risk Assessment ; }, } @article {pmid19435792, year = {2009}, author = {Henzi, T and Blum, WV and Pfefferli, M and Kawecki, TJ and Salicio, V and Schwaller, B}, title = {SV40-induced expression of calretinin protects mesothelial cells from asbestos cytotoxicity and may be a key factor contributing to mesothelioma pathogenesis.}, journal = {The American journal of pathology}, volume = {174}, number = {6}, pages = {2324-2336}, pmid = {19435792}, issn = {1525-2191}, mesh = {Antigens, Polyomavirus Transforming ; Asbestos, Crocidolite/*adverse effects ; Blotting, Western ; Calbindin 2 ; Cell Line, Tumor ; Cell Transformation, Neoplastic/chemically induced/*metabolism ; Gene Expression ; Humans ; Immunohistochemistry ; Mesothelioma/*chemically induced/*virology ; Phosphatidylinositol 3-Kinases/metabolism ; Polyomavirus Infections/complications/*metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; S100 Calcium Binding Protein G/*metabolism ; Signal Transduction/physiology ; Simian virus 40 ; Transfection ; Tumor Virus Infections/complications/metabolism ; Up-Regulation ; }, abstract = {The calcium-binding protein calretinin has emerged as a useful marker for the identification of mesotheliomas of the epithelioid and mixed types, but its putative role in tumor development has not been addressed previously. Although exposure to asbestos fibers is considered the main cause of mesothelioma, undoubtedly, not all mesothelioma patients have a history of asbestos exposure. The question as to whether the SV40 virus is involved as a possible co-factor is still highly debated. Here we show that increased expression of SV40 early gene products in the mesothelial cell line MeT-5A induces the expression of calretinin and that elevated calretinin levels strongly correlate with increased resistance to asbestos cytotoxicity. Calretinin alone mediates a significant part of this protective effect because cells stably transfected with calretinin cDNA were clearly more resistant to the toxic effects of crocidolite than mock-transfected control cells. Down-regulation of calretinin by antisense methods restored the sensitivity to asbestos toxicity to a large degree. The protective effect observed in clones with higher calretinin expression levels could be eliminated by phosphatidylinositol 3-kinase (PI3K) inhibitors, implying an important role for the PI3K/AKT signaling (survival) pathway in mediating the protective effect. Up-regulation of calretinin, resulting from either asbestos exposure or SV40 oncoproteins, may be a common denominator that leads to increased resistance to asbestos cytotoxicity and thereby contributes to mesothelioma carcinogenesis.}, } @article {pmid19432887, year = {2009}, author = {Shigematsu, Y and Hanagiri, T and Kuroda, K and Baba, T and Mizukami, M and Ichiki, Y and Yasuda, M and Takenoyama, M and Sugio, K and Yasumoto, K}, title = {Malignant mesothelioma-associated antigens recognized by tumor-infiltrating B cells and the clinical significance of the antibody titers.}, journal = {Cancer science}, volume = {100}, number = {7}, pages = {1326-1334}, pmid = {19432887}, issn = {1349-7006}, mesh = {Aged ; Aged, 80 and over ; Animals ; Antibodies, Neoplasm/*blood/immunology ; Antigens, Neoplasm/*immunology ; B-Lymphocyte Subsets/*immunology ; Cell Line, Tumor ; Female ; Humans ; Lymphocytes, Tumor-Infiltrating/*immunology ; Male ; Mesothelioma/*immunology ; Mice ; Mice, SCID ; Middle Aged ; Transplantation, Heterologous ; }, abstract = {Malignant pleural mesothelioma (MPM) is difficult to diagnose at an early stage. The present study attempted to obtain a tumor-specific antibody against MPM derived from tumor-infiltrating B lymphocytes in MPM by using a xenotransplanted severe combined immunodeficiency (SCID) mouse model, and to identify the antigens recognized by the antibodies. Among the antigen-antibody relationships, the clinical usefulness of antibody titers in the sera was evaluated from the viewpoint of diagnosis of MPM and monitoring of therapeutic effects. Tumor tissue specimens from two patients with MPM were engrafted subcutaneously in SCID mice and blood samples were obtained and pooled every 2 weeks after xenotransplantation until 14 weeks when the mice were killed. A cDNA library was constructed from the mRNA of a MPM cell line (K921MSO). Immunoscreening of the libraries was carried out by serological identification of antigens by a recombinant expression cloning method (SEREX) and four antigens were identified as MPM-associated antigens. Among them, antibody titers against two antigens, Gene-X and thrombospondin-2 (THBS-2), were analyzed by phage plaque assay as the first step. ELISA systems correlated with the phage plaque assay to detect antibody titers against the two antigens were constructed using 20-mer peptides of the antigen-coding genes. The cut-off value was decided by the average and standard deviation of normal healthy persons. Antibody against Gene-X was detected in 10 out of 18 (55.6%) mesothelioma patients and antibody against THBS-2 was detected in 16 out of 18 (88.9%) mesothelioma patients. No patients with lung cancer regardless of asbestos exposure exhibited positive antibody titer against the two antigens. Furthermore, the serum antibody titers decreased after surgical treatment of MPM and increased after recurrence of the disease. The titers of the antibodies against Gene-X and THBS-2 could be used as tumor markers for the diagnosis and follow up of patients with MPM.}, } @article {pmid19429663, year = {2009}, author = {Muller, J and Delos, M and Panin, N and Rabolli, V and Huaux, F and Lison, D}, title = {Absence of carcinogenic response to multiwall carbon nanotubes in a 2-year bioassay in the peritoneal cavity of the rat.}, journal = {Toxicological sciences : an official journal of the Society of Toxicology}, volume = {110}, number = {2}, pages = {442-448}, doi = {10.1093/toxsci/kfp100}, pmid = {19429663}, issn = {1096-0929}, mesh = {Abdominal Neoplasms/*chemically induced ; Animals ; Asbestos, Crocidolite/toxicity ; *Biological Assay/standards ; Carcinogenicity Tests/*methods/standards ; Carcinogens/*toxicity ; Cell Transformation, Neoplastic/*chemically induced ; Injections, Intraperitoneal ; Male ; Mesothelioma/*chemically induced ; Nanotubes, Carbon/chemistry/*toxicity ; Peritoneal Cavity ; Rats ; Rats, Wistar ; Reference Standards ; Risk Assessment ; Surface Properties ; Time Factors ; }, abstract = {Toxicological investigations of carbon nanotubes have shown that they can induce pulmonary toxicity, and similarities with asbestos fibers have been suggested. We previously reported that multiwall carbon nanotubes (MWCNT) induced lung inflammation, granulomas and fibrotic reactions. The same MWCNT also caused mutations in epithelial cells in vitro and in vivo. These inflammatory and genotoxic activities were related to the presence of defects in the structure of the nanotubes. In view of the strong links between inflammation, mutations and cancer, these observations prompted us to explore the carcinogenic potential of these MWCNT in the peritoneal cavity of rats. The incidence of mesothelioma and other tumors was recorded in three groups of 50 male Wistar rats injected intraperitoneally with a single dose of MWCNT with defects (2 or 20 mg/animal) and MWCNT without defects (20 mg/animal). Two additional groups of 26 rats were used as positive (2 mg UICC crocidolite/animal) and vehicle controls. After 24 months, although crocidolite induced a clear carcinogenic response (34.6% animals with mesothelioma vs. 3.8% in vehicle controls), MWCNT with or without structural defects did not induce mesothelioma in this bioassay (4, 0, or 6%, respectively). The incidence of tumors other than mesothelioma was not significantly increased across the groups. The initial hypothesis of a contrasting carcinogenic activity between MWCNT with and without defects could not be verified in this bioassay. We discuss the possible reasons for this absence of carcinogenic response, including the length of the MWCNT tested (< 1 mum on average), the absence of a sustained inflammatory reaction to MWCNT, and the capacity of these MWCNT to quench free radicals.}, } @article {pmid19425525, year = {2009}, author = {Brims, FJ}, title = {Asbestos--a legacy and a persistent problem.}, journal = {Journal of the Royal Naval Medical Service}, volume = {95}, number = {1}, pages = {4-11}, pmid = {19425525}, issn = {0035-9033}, mesh = {Asbestos/*toxicity ; Construction Materials/toxicity ; Humans ; *Military Personnel ; Occupational Diseases/*etiology ; Occupational Exposure/adverse effects ; Pleural Diseases/etiology ; United Kingdom ; Workers' Compensation/legislation & jurisprudence ; }, abstract = {Asbestos has been utilised by industrialised nations for over a century and its deleterious health effects have been reported for an almost equal length of time. Whilst developed countries have now reduced their asbestos use, developing nations are increasing their asbestos imports and consumption. Because of this, there is now a perceived risk to Non Government Organisation and military personnel involved in aid operations or conflict areas, where asbestos containing materials and buildings may have been disrupted. With significant asbestos exposures to U.K. military and dockyard personnel in the past, the health consequences are continuing to increase, with the incidence of malignant mesothelioma expected to continue to rise until between 2012-2020. There is no effective cure or treatment for any of the lung or pleural asbestos related diseases; malignant mesothelioma has a median survival of just 6-12 months. Misconceptions about asbestos are widespread, contributed in part by a long latency between exposure and disease. Following diagnosis of an asbestos related disease, financial recompense for ex-service personnel is limited, and the civilian legal implications continue to change. This review will encompass the historical usage of asbestos, its biological effects, the legal and financial implications of exposure, and establish that there may be a continuing threat of exposure to deployed military personnel}, } @article {pmid19424765, year = {2010}, author = {Harb, A and King, E and Lloyd, H and Harb, Z and Payne, JG}, title = {Primary omental mesothelioma: a rare but important differential diagnosis in previous asbestos exposure.}, journal = {Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract}, volume = {14}, number = {2}, pages = {423-425}, pmid = {19424765}, issn = {1873-4626}, mesh = {Aged ; Asbestos/adverse effects ; *Asbestosis ; Diagnosis, Differential ; Fatal Outcome ; Humans ; Male ; Mesothelioma/*diagnosis/etiology ; *Occupational Exposure ; Omentum/*pathology ; Peritoneal Neoplasms/*diagnosis ; }, abstract = {Primary omental mesothelioma is a malignant tumour of the mesothelial cells of the omentum, related to asbestos exposure. It is an extremely rare condition that presents both diagnostic and therapeutic challenges. We present a review of the related literature and report on a fatal case of primary omental mesothelioma in a 70 year old man, presenting with a painful abdominal mass. Radiological imaging was not diagnostic but useful in excluding other pathologies. Diagnosis relied on specific immunohistochemical analysis. The difficulty in diagnosis and management and the advanced stage of disease meant that prognosis was very poor. Our patient died within 3 weeks of diagnosis.}, } @article {pmid19422663, year = {2009}, author = {McCoy, MJ and Nowak, AK and Lake, RA}, title = {Chemoimmunotherapy: an emerging strategy for the treatment of malignant mesothelioma.}, journal = {Tissue antigens}, volume = {74}, number = {1}, pages = {1-10}, doi = {10.1111/j.1399-0039.2009.01275.x}, pmid = {19422663}, issn = {1399-0039}, mesh = {Antigens, Neoplasm/*immunology/metabolism ; Antineoplastic Agents/*therapeutic use ; Combined Modality Therapy ; Cytokines/immunology/metabolism ; Humans ; *Immunosuppression Therapy ; Mesothelioma/drug therapy/immunology/*therapy ; Neoplasms, Mesothelial/drug therapy/immunology/*therapy ; }, abstract = {Whether the immune system can recognize malignant and premalignant cells and eliminate them to prevent the development of cancer is still a matter of open debate, but in our view, the balance of evidence favours this concept. Nonetheless, the International Agency for Research on Cancer has now predicted that cancer will overtake heart disease as the leading cause of death worldwide by 2010, showing that this protective mechanism often fails. Malignant mesothelioma has traditionally been considered a relatively non-immunogenic cancer. However, mesothelioma cells do express a set of well-defined tumour antigens that have been shown to engage with the host immune system. Mesothelioma should therefore be considered a target for immunotherapy. A variety of anticancer immunotherapies have been investigated in mesothelioma and in other malignancies, although these have been largely ineffective when used in isolation. Over recent years, there has been increasing interest in the possibility of combining immunotherapy with chemotherapy in the fight against cancer. Here, we discuss the rationale behind combining these two, long considered antagonistic, treatment options in the context of malignant mesothelioma.}, } @article {pmid19421094, year = {2009}, author = {Ameille, J and Brochard, P and Letourneux, M and Paris, C and Pairon, JC}, title = {[Asbestos-related cancer risk in the presence of asbestosis or pleural plaques].}, journal = {Revue des maladies respiratoires}, volume = {26}, number = {4}, pages = {413-21; quiz 480, 483}, doi = {10.1016/s0761-8425(09)74046-x}, pmid = {19421094}, issn = {0761-8425}, mesh = {Asbestosis/*complications ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; *Occupational Exposure ; Pleural Diseases/*etiology ; Risk Assessment ; }, abstract = {INTRODUCTION: The relationships between benign asbestos-related diseases (asbestosis and pleural plaques) and thoracic cancers are still debated. The aim of this paper is to analyse epidemiological data which investigate this topic.

STATE OF THE ART: Published studies show that there is a significant relationship between occupational exposure to asbestos and lung cancer risk, even in the absence of abnormalities consistent with asbestos exposure on postero-anterior chest x-ray. In subjects with occupational exposure to asbestos, an increased risk of lung cancer and pleural mesothelioma is observed in subjects with pleural plaques on chest x-ray, in comparison with the general population. In exposed subjects with similar cumulative exposure to asbestos, it is not demonstrated that pleural plaques are associated with an increased risk of lung cancer or pleural mesothelioma.

PERSPECTIVES: All the analysed studies are only based on radiographic data. Their results must be confirmed by additional studies including a rigorous evaluation of the cumulative exposure to asbestos and chest CT-scans.

CONCLUSION: In the present state of knowledge, isolated pleural plaques do not justify specific medical surveillance, as compared to that required by the mere estimated cumulative exposure to asbestos.}, } @article {pmid19417672, year = {2009}, author = {Creaney, J and Robinson, BW}, title = {Serum and pleural fluid biomarkers for mesothelioma.}, journal = {Current opinion in pulmonary medicine}, volume = {15}, number = {4}, pages = {366-370}, doi = {10.1097/MCP.0b013e32832b98eb}, pmid = {19417672}, issn = {1531-6971}, mesh = {Biomarkers, Tumor/*metabolism ; GPI-Linked Proteins ; Humans ; Lung Neoplasms/*diagnosis/metabolism ; Membrane Glycoproteins/metabolism ; Mesothelin ; Mesothelioma/*diagnosis/metabolism ; Osteopontin/metabolism ; Pleural Cavity/metabolism ; Sensitivity and Specificity ; }, abstract = {PURPOSE OF REVIEW: Malignant mesothelioma is an asbestos-induced, aggressive tumour. In centres across the world, research has focused on evaluating biomarkers for malignant mesothelioma screening, diagnosis, prognostication and monitoring. With the incidence of malignant mesothelioma expected to increase, it is timely to review the current status of biomarkers in this field.

RECENT FINDINGS: The majority of recent studies have evaluated the commercial MESOMARK assay in a diagnostic setting. Studies have clarified that soluble-shed mesothelin as well as mesothelin-related peptide are targets of the assay. The assay sensitivity ranges from 50% at diagnosis to 84% in advanced disease. The assay has a high level of specificity relative to benign lung and pleural conditions and is positive in 10-15% of other malignancies. In a prospective screen of 538 asbestos-exposed workers, 2.8% were positive; one had lung cancer that was subsequently successfully treated. The biomarkers megakaryocyte potentiating factor, osteopontin and CA125, either alone or in combination with soluble mesothelin, have also been assessed.

SUMMARY: To date, soluble mesothelin remains the best available biomarker for malignant mesothelioma. However, a lack of sensitivity for early-stage disease and for all malignant mesothelioma histologies provides motivation for the search of novel malignant mesothelioma biomarkers with greater sensitivity, especially for very early disease.}, } @article {pmid19398862, year = {2009}, author = {Okura, H and Suga, Y and Akiyama, O and Kudo, K and Tsutsumi, S and Abe, Y and Yasumoto, Y and Ito, M and Izumi, H and Shiomi, K}, title = {Pleural malignant mesothelioma causing cord infiltration through the nerve root. Case report.}, journal = {Neurologia medico-chirurgica}, volume = {49}, number = {4}, pages = {167-171}, doi = {10.2176/nmc.49.167}, pmid = {19398862}, issn = {1349-8029}, mesh = {Asbestos/adverse effects ; Disease Progression ; Environmental Exposure ; Fatal Outcome ; Humans ; Laminectomy ; Magnetic Resonance Imaging ; Male ; Mesothelioma/*secondary ; Middle Aged ; Neoplasm Invasiveness/*pathology/physiopathology ; Paresis/etiology ; Pleural Neoplasms/*pathology ; Radiculopathy/etiology/*pathology/physiopathology ; Respiratory Insufficiency/etiology ; Spinal Cord/*pathology/physiopathology ; Spinal Neoplasms/*secondary ; Spinal Nerve Roots/*pathology/physiopathology ; Thoracic Vertebrae/pathology ; Urinary Incontinence/etiology ; }, abstract = {A 61-year-old man presented with a rare pleural malignant mesothelioma of the spine manifesting as progressive weakness of the bilateral lower extremities, numbness in the body and both legs, and dysfunction of the bladder and bowel. He had previous occupational exposure to asbestos while working at a car repair shop and had undergone right panpleuropneumonectomy under a diagnosis of sarcomatous type mesothelioma in the right pleural space. Magnetic resonance imaging of the spine with gadolinium showed an enhanced intramedullary tumor at the T4 level. Operative findings disclosed the clouded and swollen right posterior nerve root, and the pial surface was covered by clouded arachnoid-like membrane. The removed part of the T4 posterior nerve root and intramedullary tumor revealed malignant mesothelioma with invasion spreading along the posterior nerve root. He died of respiratory failure 3 months after the diagnosis. This case shows that spinal metastasis must be considered if a patient with pleural malignant mesothelioma shows neurological worsening and neuroimaging shows an abnormal lesion in the thoracic spinal cord. However, the patient's neurological condition is very difficult to improve in the presence of spinal cord infiltration.}, } @article {pmid19396864, year = {2009}, author = {Guled, M and Lahti, L and Lindholm, PM and Salmenkivi, K and Bagwan, I and Nicholson, AG and Knuutila, S}, title = {CDKN2A, NF2, and JUN are dysregulated among other genes by miRNAs in malignant mesothelioma -A miRNA microarray analysis.}, journal = {Genes, chromosomes & cancer}, volume = {48}, number = {7}, pages = {615-623}, doi = {10.1002/gcc.20669}, pmid = {19396864}, issn = {1098-2264}, mesh = {Aged ; Asbestos/poisoning ; Chromosomes, Human ; Cluster Analysis ; Cyclin-Dependent Kinase Inhibitor p16/*genetics/metabolism ; Female ; Gene Expression Profiling/methods ; *Gene Expression Regulation, Neoplastic ; Humans ; Male ; Mesothelioma/*genetics/metabolism/pathology ; MicroRNAs/biosynthesis/*genetics/metabolism ; Middle Aged ; Neurofibromin 2/*genetics/metabolism ; Oligonucleotide Array Sequence Analysis/methods ; Proto-Oncogene Proteins c-jun/*genetics/metabolism ; Risk Factors ; Smoking/genetics/metabolism ; Survival Analysis ; }, abstract = {Malignant mesothelioma (MM) is an aggressive cancer arising from mesothelial cells, mainly due to former asbestos exposure. Little is known about the microRNA (miRNA) expression of MM. miRNAs are small noncoding RNAs, which play an essential role in the regulation of gene expression. This study was carried out to analyze the miRNA expression profile of 17 MM samples using miRNA microarray. The analysis distinguished the overall miRNA expression profiles of tumor tissue and normal mesothelium. Differentially expressed miRNAs were found in tumor samples compared with normal sample. Twelve of them, let-7b*, miR-1228*, miR-195*, miR-30b*, miR-32*, miR-345, miR-483-3p, miR-584, miR-595, miR-615-3p, and miR-885-3p, were highly expressed whereas the remaining nine, let-7e*, miR-144*, miR-203, miR-340*, miR-34a*, miR-423, miR-582, miR-7-1*, and miR-9, were unexpressed or had severely reduced expression levels. Target genes for these miRNAs include the most frequently affected genes in MM such as CDKN2A, NF2, JUN, HGF, and PDGFA. Many of the miRNAs were located in chromosomal areas known to be deleted or gained in MM such as 8q24, 1p36, and 14q32. Furthermore, we could identify specific miRNAs for each histopathological subtype of MM. Regarding risk factors such as smoking status and asbestos exposure, significantly differentially expressed miRNAs were identified in smokers versus nonsmokers (miR-379, miR-301a, miR-299-3p, miR-455-3p, and miR-127-3p), but not in asbestos-exposed patients versus nonexposed ones. This could be related to the method of assessment of asbestos exposure as asbestos remains to be the main contributor to the development of MM.}, } @article {pmid19390506, year = {2009}, author = {, }, title = {Malignant mesothelioma mortality--United States, 1999-2005.}, journal = {MMWR. Morbidity and mortality weekly report}, volume = {58}, number = {15}, pages = {393-396}, pmid = {19390506}, issn = {1545-861X}, mesh = {Adult ; Age Factors ; Aged ; *Asbestos ; Cause of Death ; Female ; Humans ; Male ; Mesothelioma/*mortality ; Middle Aged ; *Occupational Exposure ; Retrospective Studies ; United States/epidemiology ; }, abstract = {Malignant mesothelioma is a fatal cancer primarily associated with exposure to asbestos. The latency period between first exposure to asbestos and clinical disease usually is 20--40 years. Although asbestos is no longer mined in the United States, the mineral is still imported, and a substantial amount of asbestos remaining in buildings eventually will be removed, either during remediation or demolition. Currently, an estimated 1.3 million construction and general industry workers potentially are being exposed to asbestos. To characterize mortality attributed to mesothelioma, CDC's National Institute for Occupational Safety and Health (NIOSH) analyzed annual multiple-cause-of-death records for 1999--2005, the most recent years for which complete data are available. For those years, a total of 18,068 deaths of persons with malignant mesothelioma were reported, increasing from 2,482 deaths in 1999 to 2,704 in 2005, but the annual death rate was stable (14.1 per million in 1999 and 14.0 in 2005). Maintenance, renovation, or demolition activities that might disturb asbestos should be performed with precautions that sufficiently prevent exposures for workers and the public. In addition, physicians should document the occupational history of all suspected and confirmed mesothelioma cases.}, } @article {pmid19383114, year = {2009}, author = {Sahin, U and Ozturk, O and Songur, N and Bircan, A and Akkaya, A}, title = {Observations on environmental asbestos exposure in a high risk area.}, journal = {Respirology (Carlton, Vic.)}, volume = {14}, number = {4}, pages = {579-582}, doi = {10.1111/j.1440-1843.2009.01493.x}, pmid = {19383114}, issn = {1440-1843}, mesh = {Adult ; Aged ; Asbestos/*adverse effects/analysis ; Asbestosis/*epidemiology/genetics ; *Carcinogens ; Cluster Analysis ; Environmental Exposure/adverse effects/*statistics & numerical data ; Female ; Humans ; Lung Neoplasms/*epidemiology/genetics ; Male ; Mesothelioma/*epidemiology/genetics ; Middle Aged ; Pedigree ; Risk Factors ; Soil/analysis ; Turkey ; }, abstract = {BACKGROUND AND OBJECTIVE: Environmental asbestos exposure is causally associated with various pulmonary pathologies. In Turkey, one of the most important sources of asbestos exposure is dust originating from the walls of homes whitewashed with white stucco. The main asbestos types implicated are tremolite and, to a lesser extent, chrysotile. This study investigated the presence and effect of environmental asbestos exposure in a small village in Isparta, Turkey.

METHODS: Samples of asbestos mine ore, whitewashed plaster from the interior walls of the houses and whitesoil from the outside walls of the houses were analysed. Chest radiographs of 132 villagers aged 30 years and over and living in the village during the study were obtained. Verbal histories from the relatives of people who had died from lung cancer or mesothelioma and hospital records contributed 13 cases to the study population, giving a total of 145 cases under study.

RESULTS: Chrysotile fibres were found in the old asbestos mine sample, and zeolite in the whitesoil sample from the outside walls. Abnormal CXR were found in 19 subjects (14. 4%), the most common being pleural calcifications and/or pleural plaques (n = 14, 10.6%). A further five subjects with pleural calcifications and/or pleural plaques were identified from verbal autopsy and hospital records. Malignant pleural mesothelioma was present in one living subject and four of the deaths. A possible familial clustering of lung cancer and malignant mesothelioma was noted.

CONCLUSION: While tremolite asbestos is the asbestos found in most white soil in Turkey, in this village chrysotile asbestos was found in the white soil. Familial clustering may indicate genetic susceptibility or increased environmental exposure in some families.}, } @article {pmid19382522, year = {2009}, author = {Merler, E and Bressan, V and Somigliana, A and , }, title = {[Mesothelioma in construction workers: risk estimate, lung content of asbestos fibres, claims for compensation for occupational disease in the Veneto Region mesothelioma register].}, journal = {La Medicina del lavoro}, volume = {100}, number = {2}, pages = {120-132}, pmid = {19382522}, issn = {0025-7818}, mesh = {Aged ; Asbestos/*analysis ; Female ; Humans ; Italy ; Lung/*chemistry ; Male ; Mesothelioma/*epidemiology ; Mineral Fibers/*analysis ; Occupational Diseases/*epidemiology ; *Registries ; Risk Assessment ; Workers' Compensation/*statistics & numerical data ; }, abstract = {BACKGROUND: Work in the construction industry is causing the highest number of mesotheliomas among the residents of the Veneto Region (north-east Italy, 4,5 million inhabitants).

OBJECTIVES: To sum up the results on occurrence, asbestos exposure, lung fibre content analyses, and compensation for occupational disease.

METHODS: Case identification and asbestos exposure classification: active search of mesotheliomas that were diagnosed via histological or cytological examinations occurring between 1987 and 2006; a probability of asbestos exposure was attributed to each case, following interviews with the subjects or their relatives and collection of data on the jobs held over their lifetime. Risk estimate among construction workers: the ratio between cases and person-years, the latter derived from the number of construction workers reported by censuses. Lung content of asbestos fibres: examination of lung specimens by Scanning Electron Microscope to determine number and type of fibres. Claims for compensation and compensation awarded: data obtained from the National Institute for Insurance against Occupational Diseases available for the period 1999-2006.

RESULTS: of 952 mesothelioma cases classified as due to asbestos exposure, 251 were assigned to work in the construction industry (21 of which due to domestic of environmental exposures), which gives a rate of 4.1 (95% CI 3.6-4.8) x 10(5) x year among construction workers. The asbestos fibre content detected in the lungs of 11 construction workers showed a mean of 1.7 x 10(6) fibres/g dry tissue (range 350,000-3 million) for fibres > 1 micro, almost exclusively due to amphibole fibres. 62% of the claims for compensation were granted but the percentage fell to less than 40% when claims were submitted by a relative, after the death of the subject.

CONCLUSION: The prevalence of mesothelioma occurring among construction workers is high and is associated with asbestos exposure; the risk is underestimated by the subjects and their relatives. All mesotheliomas occurring among construction workers should be granted compensation for occupational disease.}, } @article {pmid19380521, year = {2009}, author = {Kawaguchi, K and Murakami, H and Taniguchi, T and Fujii, M and Kawata, S and Fukui, T and Kondo, Y and Osada, H and Usami, N and Yokoi, K and Ueda, Y and Yatabe, Y and Ito, M and Horio, Y and Hida, T and Sekido, Y}, title = {Combined inhibition of MET and EGFR suppresses proliferation of malignant mesothelioma cells.}, journal = {Carcinogenesis}, volume = {30}, number = {7}, pages = {1097-1105}, doi = {10.1093/carcin/bgp097}, pmid = {19380521}, issn = {1460-2180}, mesh = {Cell Line, Tumor ; Cell Proliferation/*drug effects ; ErbB Receptors/antagonists & inhibitors/*metabolism ; Humans ; Mesothelioma/*metabolism/pathology ; Neoplasm Invasiveness ; Phosphorylation ; Pleural Neoplasms/*metabolism/pathology ; Proto-Oncogene Proteins c-met/antagonists & inhibitors/*metabolism ; Receptor, ErbB-2/antagonists & inhibitors/metabolism ; Receptor, Platelet-Derived Growth Factor beta/antagonists & inhibitors/metabolism ; Signal Transduction/drug effects/physiology ; Up-Regulation ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive neoplasm associated with asbestos exposure. Although expression and activation of receptor tyrosine kinases (RTKs), including MET, have been reported in most MPM, specific RTK inhibitors showed less than the expected response in MPM cells. To determine whether the lack of response of MET inhibitors was due to cooperation with other RTKs, we determined activation status of MET and other RTKs, including epidermal growth factor receptor (EGFR) family of 20 MPM cell lines, and tested whether dual RTK inhibition is an effective therapeutic strategy. We detected MET upregulation and phosphorylation (thus indicating activation) in 14 (70%) and 13 (65%) cell lines, but treatment with MET-specific inhibitors showed weak or modest effect of suppression in most of the cell lines. Phospho-RTK array analysis revealed that MET was simultaneously activated with other RTKs, including EGFR, ErbB2, ErbB3 and platelet-derived growth factor receptor-beta. Combination of MET and EGFR inhibitors triggered stronger inhibition on cell proliferation and invasion of MPM cells than that of each in vitro. These results indicated that coactivation of RTKs was essential in mesothelioma cell proliferation and/or survival, thus suggesting that simultaneous inhibition of RTKs may be a more effective strategy for the development of molecular target therapy for MPM.}, } @article {pmid19380173, year = {2010}, author = {Røe, OD and Anderssen, E and Sandeck, H and Christensen, T and Larsson, E and Lundgren, S}, title = {Malignant pleural mesothelioma: genome-wide expression patterns reflecting general resistance mechanisms and a proposal of novel targets.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {67}, number = {1}, pages = {57-68}, doi = {10.1016/j.lungcan.2009.03.016}, pmid = {19380173}, issn = {1872-8332}, mesh = {Antineoplastic Agents/pharmacology/therapeutic use ; Asbestos/toxicity ; Drug Resistance, Neoplasm/drug effects/*genetics ; *Gene Expression Regulation, Neoplastic ; Genome-Wide Association Study ; Humans ; Mesothelioma/chemically induced/drug therapy/*genetics ; Pleural Neoplasms/chemically induced/drug therapy/*genetics ; Radiation Tolerance/drug effects/*genetics ; }, abstract = {Malignant pleural mesothelioma is an asbestos-related multi-resistant tumour with increasing incidence worldwide. Well-characterized snap-frozen normal parietal, visceral pleura and mesothelioma samples were analysed with Affymetrix Human Genome U133 Plus 2.0 GeneChip oligoarray of 38500 genes. We discovered a close relation between gene profile and resistance towards topoisomerase poisons, alkylating agents, antitubulines, antifolates, platinum compounds and radiation therapy. Target genes of chemo- (e.g. TOP2A, BIRC5/Survivin and proteasome) and radiotherapy (e.g. BRCA2, FANCA, FANCD2, CCNB1 and RAD50) were significantly overexpressed. The Fanconi anemia/BRCA2 pathway, responsible for homologous recombination DNA repair appears as a key pathway in both chemo- and radio-resistance of mesothelioma. Leukocyte trans-endothelial migration gene down-regulation could partly explain resistance against immunological therapies. Gene expression features found in other resistant cancer types related to DNA repair and replication are shared by mesothelioma and could represent general features of tumour resistance. Targeted suppression of some of those key genes and pathways combined with chemotherapy or radiation could improve the outcome of mesothelioma therapy. We propose CHEK1, RAD21, FANCD2 and RAN as new co-targets for mesothelioma treatment. The pro-angiogenic AGGF1 mRNA and protein was highly overexpressed in all tumours and may serve as a target for anti-angiogenic treatment. Overexpression of NQO1 may render mesothelioma sensitive to the novel compound beta-Lapachone.}, } @article {pmid19375815, year = {2010}, author = {Andujar, P and Wang, J and Descatha, A and Galateau-Sallé, F and Abd-Alsamad, I and Billon-Galland, MA and Blons, H and Clin, B and Danel, C and Housset, B and Laurent-Puig, P and Le Pimpec-Barthes, F and Letourneux, M and Monnet, I and Régnard, JF and Renier, A and Zucman-Rossi, J and Pairon, JC and Jaurand, MC}, title = {p16INK4A inactivation mechanisms in non-small-cell lung cancer patients occupationally exposed to asbestos.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {67}, number = {1}, pages = {23-30}, doi = {10.1016/j.lungcan.2009.03.018}, pmid = {19375815}, issn = {1872-8332}, mesh = {Aged ; Asbestos/*toxicity ; Carcinogens/*toxicity ; Carcinoma, Non-Small-Cell Lung/*chemically induced/genetics/metabolism ; Cyclin-Dependent Kinase Inhibitor p16/*antagonists & inhibitors/*genetics/metabolism ; DNA Methylation ; Female ; *Gene Deletion ; Humans ; Loss of Heterozygosity ; Lung Neoplasms/*chemically induced/genetics/metabolism ; Male ; Middle Aged ; *Occupational Exposure ; Promoter Regions, Genetic/drug effects ; Smoking ; }, abstract = {Epidemiological studies have shown that asbestos fibers constitute the major occupational risk factor and that asbestos acts synergistically with tobacco smoking to induce lung cancer. Although some somatic gene alterations in lung cancer have been linked to tobacco smoke, few data are available on the role of asbestos fibers. P16/CDKN2A is an important tumor suppressor gene that is frequently altered in lung cancer via promoter 5'-CpG island hypermethylation and homozygous deletion, and rarely via point mutation. Many studies suggest that tobacco smoking produces P16/CDKN2A promoter hypermethylation in lung cancer, but the status of this gene in relation to asbestos exposure has yet to be determined. The purpose of this study was to investigate the mechanism of P16/CDKN2A alterations in lung cancer in asbestos-exposed patients. P16/CDKN2A gene status was studied in 75 human non-small-cell lung cancer (NSCLC) cases with well-defined smoking habits, and detailed assessment of asbestos exposure, based on occupational questionnaire and determination of asbestos bodies in lung tissue. The results of this study confirm published data on the effect of tobacco smoke on P16/CDKN2A gene alterations, characterized by significantly higher P16/CDKN2A promoter hypermethylation in heavy smokers (more than 40 pack-years (P-Y)) than in smokers of less than 40 P-Y. These results also demonstrate a higher incidence of loss of heterozygosity and homozygous deletion in asbestos-exposed cases, after adjustment for age and cumulative tobacco consumption, than in unexposed cases (P=0.0062). This study suggests that P16/CDKN2A gene inactivation in asbestos-exposed NSCLC cases mainly occurs via deletion, a feature also found in malignant mesothelioma, a tumor independent of tobacco smoking but associated with asbestos exposure, suggesting a possible relationship with an effect of asbestos fibers.}, } @article {pmid19374599, year = {2009}, author = {Zucali, PA and De Vincenzo, F and Simonelli, M and Santoro, A}, title = {Future developments in the management of malignant pleural mesothelioma.}, journal = {Expert review of anticancer therapy}, volume = {9}, number = {4}, pages = {453-467}, doi = {10.1586/era.09.2}, pmid = {19374599}, issn = {1744-8328}, mesh = {Animals ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Biomarkers, Tumor ; Cisplatin/administration & dosage ; Clinical Trials, Phase III as Topic/statistics & numerical data ; Combined Modality Therapy ; Diagnostic Imaging ; Disease Management ; Drug Delivery Systems ; Forecasting ; Glutamates/administration & dosage ; Guanine/administration & dosage/analogs & derivatives ; Humans ; Mesothelioma/diagnosis/pathology/*therapy ; Mice ; Multicenter Studies as Topic/statistics & numerical data ; Neoplasm Proteins/antagonists & inhibitors ; Neoplasm Staging ; Pemetrexed ; Pleural Neoplasms/diagnosis/pathology/*therapy ; Quinazolines/administration & dosage ; Radiotherapy, Intensity-Modulated ; Randomized Controlled Trials as Topic/statistics & numerical data ; Thiophenes/administration & dosage ; Thoracic Surgical Procedures ; Vinblastine/analogs & derivatives ; Vinorelbine ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive tumor with a poor prognosis and an increasing incidence as a result of widespread exposure to asbestos. In the past few years, there have been several developments in the management of patients with MPM, including more accurate staging and patient selection, improvements in surgical techniques and postoperative care, novel chemotherapy regimens and new radiotherapy techniques. However, chemotherapy remains the mainstay of treatment, considering that surgery and radiotherapy have a limited role in highly selected patients, and its results are still modest, with a median survival of approximately 1 year. The principal goals of this review are to summarize the improvements in the management of MPM that have been achieved recently and to outline the therapeutic approaches in development.}, } @article {pmid19373910, year = {2009}, author = {Wheeler, YY and Burroughs, F and Li, QK}, title = {Fine-needle aspiration of a well-differentiated papillary mesothelioma in the inguinal hernia sac: A case report and review of literature.}, journal = {Diagnostic cytopathology}, volume = {37}, number = {10}, pages = {748-754}, doi = {10.1002/dc.21084}, pmid = {19373910}, issn = {1097-0339}, mesh = {Biopsy, Fine-Needle ; Hernia, Inguinal/complications/*pathology/surgery ; Humans ; Immunohistochemistry ; Inguinal Canal/*pathology/surgery ; Male ; Mesothelioma/complications/*pathology/surgery ; Middle Aged ; Peritoneal Neoplasms/complications/*pathology/surgery ; Testicular Hydrocele/surgery ; Urologic Surgical Procedures, Male/adverse effects ; }, abstract = {Well-differentiated papillary mesothelioma (WDPM) is an uncommon subtype of epithelioid mesothelioma. In contrast to malignant epithelioid mesothelioma, WDPM has a low malignant potential and an indolent clinical course. WDPM may be difficult to diagnose and differentiate from benign reactive mesothelial cells and other malignant neoplasm on cytology specimens due to the presence of papillary or tubulopapillary clusters of tumor cells. We report a case of a 63-year-old Asian male with a slowly growing left inguinal hernia mass for several years and a concurrent 8 cm mass in the peritoneal wall. The cytology of ultrasound-guided fine-needle aspiration (FNA) of the left inguinal hernia and peritoneal masse reveal cellular specimens with numerous individual and tubulopapillary clusters of epithelioid mesothelial cells in a background of scant hyalinized material. Tumor cells show minimal cytological atypia. The differential diagnoses are broad and include reactive mesothelial cells, WDPM, and other malignant neoplasm. The follow-up surgical resection of masses reveals features of WDMP. It is important to recognize this entity in the differential diagnosis, because the clinical management of WDPM is quite different from that of malignant neoplasm. On the basis of the published data in the literature, it suggests that in male patients, the WDPM occurs predominantly in pleural cavity of older men in their 50s, and about half of the patients have history of asbestos exposure. However, the data is limited and insufficient for a definitive conclusion.}, } @article {pmid19367050, year = {2009}, author = {Phillips, JI and Murray, J}, title = {South African data on malignant mesothelioma.}, journal = {Industrial health}, volume = {47}, number = {2}, pages = {198-199}, doi = {10.2486/indhealth.47.198}, pmid = {19367050}, issn = {1880-8026}, mesh = {Air Pollutants, Occupational/toxicity ; Asbestos/toxicity ; Asbestosis/*epidemiology ; Autopsy/statistics & numerical data ; Causality ; Comorbidity ; Global Health ; Humans ; Incidence ; Lung Neoplasms/*epidemiology/etiology ; Mesothelioma/*epidemiology/etiology ; *Mining ; Occupational Exposure/*statistics & numerical data ; Risk Factors ; South Africa/epidemiology ; }, } @article {pmid19367039, year = {2009}, author = {Ahn, YS and Kang, SK}, title = {Asbestos-related occupational cancers compensated under the Industrial Accident Compensation Insurance in Korea.}, journal = {Industrial health}, volume = {47}, number = {2}, pages = {113-122}, doi = {10.2486/indhealth.47.113}, pmid = {19367039}, issn = {1880-8026}, mesh = {Adenocarcinoma/epidemiology ; Adult ; Aged ; Asbestos/*toxicity ; Asbestosis/economics/*epidemiology ; Carcinoma, Large Cell/epidemiology ; Carcinoma, Small Cell/epidemiology ; Carcinoma, Squamous Cell/epidemiology ; Causality ; Comorbidity ; Compensation and Redress ; Environmental Monitoring ; Epidemiological Monitoring ; Female ; Humans ; Incidence ; Korea/epidemiology ; Lung Neoplasms/economics/*epidemiology ; Male ; Manufactured Materials/toxicity ; Mesothelioma/economics/*epidemiology ; Metallurgy/statistics & numerical data ; Middle Aged ; Occupational Diseases/*epidemiology ; Occupational Exposure/*analysis ; Ships ; Smoking/epidemiology ; Workers' Compensation/*statistics & numerical data ; }, abstract = {Compensation for asbestos-related cancers occurring in occupationally-exposed workers is a global issue; this is also an issue in Korea. To provide basic information regarding compensation for workers exposed to asbestos, 60 cases of asbestos-related occupational lung cancer and mesothelioma that were compensated during 15 yr; from 1993 (the year the first case was compensated) to 2007 by the Korea Labor Welfare Corporation (KLWC) are described. The characteristics of the cases were analyzed using the KLWC electronic data and the epidemiologic investigation data conducted by the Occupational Safety and Health Research Institute (OSHRI) of the Korea Occupational Safety and Health Agency (KOSHA). The KLWC approved compensation for 41 cases of lung cancer and 19 cases of mesothelioma. Males accounted for 91.7% (55 cases) of the approved cases. The most common age group was 50-59 yr (45.0%). The mean duration of asbestos exposure for lung cancer and mesothelioma cases was 19.2 and 16.0 yr, respectively. The mean latency period for lung cancer and mesothelioma cases was 22.1 and 22.6 yr, respectively. The major industries associated with mesothelioma cases were shipbuilding and maintenance (4 cases) and manufacture of asbestos textiles (3 cases). The major industries associated with lung cancer cases were shipbuilding and maintenance (7 cases), construction (6 cases), and manufacture of basic metals (4 cases). The statistics pertaining to asbestos-related occupational cancers in Korea differ from other developed countries in that more cases of mesothelioma were compensated than lung cancer cases. Also, the mean latency period for disease onset was shorter than reported by existing epidemiologic studies; this discrepancy may be related to the short history of occupational asbestos use in Korea. Considering the current Korean use of asbestos, the number of compensated cases in Korea is expected to increase in the future but not as much as developed countries.}, } @article {pmid19358470, year = {2009}, author = {Toyokuni, S}, title = {Mechanisms of asbestos-induced carcinogenesis.}, journal = {Nagoya journal of medical science}, volume = {71}, number = {1-2}, pages = {1-10}, pmid = {19358470}, issn = {0027-7622}, mesh = {Animals ; Asbestos/*adverse effects ; Asbestosis/epidemiology/*genetics/*metabolism ; *Carcinogens ; Chromosome Aberrations ; Humans ; Iron/metabolism ; Lung Neoplasms/epidemiology/genetics/metabolism ; Mesothelioma/epidemiology/genetics/metabolism ; Oxidative Stress/physiology ; }, abstract = {Respiratory exposure to asbestos fibers has been associated with diffuse malignant mesothelioma (DMM) in humans. Despite advancements in the molecular analyses of human DMM and the development of animal models, the carcinogenic mechanisms of the disease remain unclear. There are basically three hypotheses regarding the pathogenesis of asbestos-induced DMM, which may be summarized as follows: (1) the "oxidative stress theory" is based on the fact that phagocytic cells that engulf asbestos fibers produce large amounts of free radicals due to their inability to digest the fibers, and epidemiological studies indicating that iron-containing asbestos fibers appear more carcinogenic; (2) the "chromosome tangling theory" postulates that asbestos fibers damage chromosomes when cells divide; and (3) the "theory of adsorption of many specific proteins as well as carcinogenic molecules" states that asbestos fibers in vivo concentrate proteins or chemicals including the components of cigarette smoke. Elucidation of the major mechanisms underlying DMM would be helpful for the development of novel strategies to prevent DMM induction in people who have already been exposed to asbestos.}, } @article {pmid19358359, year = {2009}, author = {Pylev, LN and Smirnova, OV and Vasil'eva, LA}, title = {[Effect of peptone blocking asbestos-induced carcinogenesis in rats].}, journal = {Gigiena i sanitariia}, volume = {}, number = {1}, pages = {65-67}, pmid = {19358359}, issn = {0016-9900}, mesh = {Animals ; Asbestos/*toxicity ; Carcinogenicity Tests ; Disease Models, Animal ; Female ; Injections, Intraperitoneal ; Male ; Mesothelioma/chemically induced/pathology/*prevention & control ; Neoplasms, Experimental/chemically induced/pathology/*prevention & control ; Peptones/*administration & dosage ; Peritoneal Neoplasms/chemically induced/pathology/*prevention & control ; Rats ; Rats, Wistar ; }, abstract = {Regular intraperitoneal administration of peptone to rats was initiated immediately and 12 months after intraperitoneal thrice injection of crokidolite UICC in a dose of 20 mg. The rate of peritoneal mesotheliomas was 37.8% after co-administration of peptone and crokidolite, 25.6% following 12 months of crokidolite injection, and 72.1% after use of crokidolite alone. The effect of peptone administration is accounted for by the action of macrophages on transformed mesothelial cells and mesothelioma cells.}, } @article {pmid19357540, year = {2009}, author = {Roberts, HC and Patsios, DA and Paul, NS and DePerrot, M and Teel, W and Bayanati, H and Shepherd, F and Johnston, MR}, title = {Screening for malignant pleural mesothelioma and lung cancer in individuals with a history of asbestos exposure.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {4}, number = {5}, pages = {620-628}, doi = {10.1097/JTO.0b013e31819f2e0e}, pmid = {19357540}, issn = {1556-1380}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; *Carcinogens ; Female ; Follow-Up Studies ; Humans ; Incidence ; Lung Neoplasms/*diagnostic imaging/etiology ; Male ; Mass Screening ; Mesothelioma/*diagnostic imaging/etiology ; Middle Aged ; Neoplasm Staging ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*diagnostic imaging/etiology ; Prognosis ; Solitary Pulmonary Nodule/pathology ; Survival Rate ; *Tomography, X-Ray Computed ; Young Adult ; }, abstract = {PURPOSE: We established a screening program for prior asbestos workers using low-dose computed tomography (LDCT).

METHODS: Between March 2005 and October 2007 we performed LDCT (50-60 mA, 120 kV, 1.25 mm) in 516 asbestos-exposed individuals. Parenchymal nodules were followed according to lung cancer screening recommendations, morphology and location of pleural plaques was noted in detail.

RESULTS: We included 507 men and 9 women (median 60.0 years), 395 (76.6%) were smokers. Annual repeat has been performed in 356 participants. We found plaques in 357 subjects (69.2%), commonly calcified (79.6%), flat (86.6%), and symmetric (86.8%), and mostly involving the costal (96.4%) and diaphragmatic (81.8%) pleura. Uncommon plaques were lobulated (13.2%), right-dominant asymmetric (4.5%), or with effusions (0.1%).We found pulmonary nodules in 371 subjects (71.9%), 91 (17.6%) had at least one nodule > or =5 mm; 10 growing nodules were found on annual repeat LDCT. In 41 individuals, plaques were regarded as atypical; three had new pleural/peritoneal abnormalities on annual repeat LDCT. An interim limited computed tomography of the observed abnormality prompted 10 diagnostic biopsies, resulting in a diagnosis of six lung cancers, two pleural mesothelioma and two peritoneal mesothelioma; overall rate of screen-detected malignancies is 2.1%. There were four interval cancers, diagnosed after baseline (n = 1) or after the annual repeat (n = 3): two pleural and one peritoneal mesothelioma, and one mixed squamous/small cell carcinoma.

CONCLUSION: Screening prior asbestos workers detects advanced malignant pleural mesothelioma and early as well as late stage lung cancer. We expect to learn more about the appearance of "early mesothelioma" with continued screening.}, } @article {pmid19353958, year = {2008}, author = {Terracini, B}, title = {[Rotterdam Convention: chrysotile is still in the waiting list].}, journal = {Epidemiologia e prevenzione}, volume = {32}, number = {6}, pages = {275-276}, pmid = {19353958}, issn = {1120-9763}, mesh = {Asbestos, Serpentine/*adverse effects ; Asbestosis/*etiology ; Chemical Industry/standards ; Consensus Development Conferences as Topic ; Environmental Exposure/*adverse effects ; Health Surveys ; Humans ; Internationality ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Netherlands ; Practice Guidelines as Topic ; United Nations/legislation & jurisprudence ; }, } @article {pmid19349911, year = {2009}, author = {Helmig, S and Belwe, A and Schneider, J}, title = {Association of transforming growth factor beta1 gene polymorphisms and asbestos-induced fibrosis and tumors.}, journal = {Journal of investigative medicine : the official publication of the American Federation for Clinical Research}, volume = {57}, number = {5}, pages = {655-661}, doi = {10.2310/JIM.0b013e3181a4f32a}, pmid = {19349911}, issn = {1081-5589}, mesh = {Adult ; Aged ; Aged, 80 and over ; Alleles ; Asbestos/*adverse effects ; Asbestosis/*genetics ; Base Sequence ; Case-Control Studies ; DNA Primers/genetics ; Gene Frequency ; Genotype ; Humans ; Lung Neoplasms/etiology/*genetics ; Male ; Mesothelioma/etiology/genetics ; Middle Aged ; Polymorphism, Single Nucleotide ; Silicosis/genetics ; Transforming Growth Factor beta1/*genetics ; Young Adult ; }, abstract = {AIM: Inhaled asbestos fibers are known to cause progressive lung or pleural fibrosis and malignancies such as lung cancer or diffuse malignant mesothelioma. Transforming growth factor beta1 (TGF-beta1), a multifunctional cytokine, regulates the proliferation and differentiation of cells. Transforming growth factor beta1 is known to promote the pathogenesis of lung fibrosis and acts as a tumor suppressor in normal cells. Two genetic polymorphisms in codons 10 (Leu10Pro) and 25 (Arg25Pro) of the TGF-beta1 gene are suggested to be associated with a different TGF-beta1 protein production. Therefore, we examined an association between the 2 TGF-beta1 gene polymorphisms and asbestos-induced lung fibrosis and lung cancer.

METHODS: Detection of the 2 polymorphisms was performed by rapid capillary polymerase chain reaction, with melting curve analysis, using fluorescence-labeled hybridization probes. To investigate the association between TGF-beta1 gene polymorphisms in codons 10 and 25 and the susceptibility to asbestos-induced diseases, association studies were performed with healthy control subjects (n = 83), patients with pulmonary fibrosis (n = 591), and patients with bronchial carcinoma (n = 147).

RESULTS: Compared with a healthy control group, odds ratio (OR) analysis revealed an inverse relationship for the proline allele at codon 10 or 25 with pulmonary fibrosis (higher risk) and lung cancer (lower risk). The proline allele at codon 10 or 25 is significantly associated with a higher risk for fibrotic lung diseases (ORcrude, 1.46; 95% confidence interval [CI], 1.01-2.11; P = 0.045 and ORadjusted, 1.76; 95% CI, 1.14-2.72; P = 0.011, respectively, for codon 10; OR, 2.13; 95% CI, 1.33-3.99; P = 0.019 and ORadjusted, 2.27; 95% CI, 1.14-4.52; P = 0.02, respectively, for codon 25) when compared with patients with lung cancer. A significant association for the proline allele is also revealed when comparing patients with asbestosis (ORcrude, 3.01; 95% CI, 1.44-6.29; P = 0.003 and ORadjusted, 3.72; 95% CI, 1.56-8.85; P = 0.011) with patients with asbestos-induced lung cancer.

CONCLUSIONS: In summary, the results confirm the hypothesis that TGF-beta1 polymorphisms are associated with asbestos-induced fibrotic or malignant lung diseases in whites.}, } @article {pmid19346724, year = {2009}, author = {Fukuyama, T and Kawahara, H and Yamada, M and Hayashi, N and Yano, H and Fukura, M and Ozaki, K and Tsuchishima, M and Takase, S and Arisawa, T and Omote, K and Nojima, T}, title = {[A case of IL-6 producing malignant mesothelioma of abdomen with thrombocytosis].}, journal = {Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology}, volume = {106}, number = {4}, pages = {546-553}, pmid = {19346724}, issn = {0446-6586}, mesh = {Abdominal Neoplasms/complications/drug therapy/*metabolism ; Aged ; Humans ; Interleukin-6/*biosynthesis/blood ; Male ; Mesothelioma/complications/drug therapy/*metabolism ; Thrombocytosis/complications ; }, abstract = {A 77-year-old man was admitted to our hospital with abdominal pain and ascites. He had an occupational history of working with asbestos. Abdominal CT showed multiple nodular lesions with enhancement by contrast medium in the cavity. Platelet counts, CRP and serum IL-6 level were increased. Biopsied materials obtained by laparoscopy showed oval cells with rich cytoplasm growing in an epithelial pattern. To clarify the characteristics of the cells, immunohistochemistry was performed. Calretinin and CK5/6 were positive, and CEA, S-100 protein, c-kit and CD34 were negative, result in confirmation of a diagnosis of malignant mesothelioma. Because IL-6, IL-6 receptor and VEGF were expressed markedly, the patient received chemotherapy for IL-6 suppression. During the treatment, thrombocytosis imploved satisfactorily.}, } @article {pmid19346221, year = {2009}, author = {Neragi-Miandoab, S and Sugarbaker, DJ}, title = {Chromosomal deletion in patients with malignant pleural mesothelioma.}, journal = {Interactive cardiovascular and thoracic surgery}, volume = {9}, number = {1}, pages = {42-44}, doi = {10.1510/icvts.2008.201509}, pmid = {19346221}, issn = {1569-9285}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Carcinogens ; *Chromosome Deletion ; Female ; *Gene Expression Regulation, Neoplastic ; Genetic Predisposition to Disease ; Humans ; Karyotyping ; Loss of Heterozygosity ; Male ; Mesothelioma/*genetics/pathology ; Middle Aged ; Pleural Neoplasms/*genetics/pathology ; Retrospective Studies ; Risk Factors ; }, abstract = {Malignant pleural mesothelioma (MPM) is associated with frequent deletions of specific chromosomal regions within 1p, 3p, 6q, 9p, 13q, 15q, and 22q. In this retrospective review of our patients with MPM, the tumor tissue of 40 patients (31 male and 9 female) was evaluated for chromosomal deletions and was karyotyped. Chromosomal deletions in regions 1p, 3p, 6p, 9p, 6q, 9q, 22q were observed in 22 of 40 patients (55%). Of this group of 22 patients, 15 (68%) demonstrated deletions in chromosome 6; 12 (54%) exhibited deletions in chromosome 22q; and 13 (59%) had deletions in chromosome 9p. Asbestos exposure was found in only 13 of the 22 patients (59%) with chromosomal deletions. There was no correlation between asbestos exposure and chromosomal deletion (95% CI -0.38-0.23, P=0.63). Chromosomal deletion did not correlate with age (95% CI -0.45-0.14, P=0.29). The majority of patients with chromosomal deletions had epithelial histology (17 of 22 patients; 77%), which was not statistically significant (95% CI -0.14-0.46, P=0.27). Chromosomal deletion is common in tumor tissue of MPM and the inactivation of tumor suppressor genes (TSGs) residing in these chromosomes may contribute to mesothelial cell tumorigenesis.}, } @article {pmid19344084, year = {2008}, author = {Barbieri, PG and Somigliana, A and Lombardi, S and Girelli, R and Rocco, A and Pezzotti, C and Silvestri, S}, title = {[Recycle of jute bags; asbestos in agriculture, exposure and pathology ].}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {30}, number = {4}, pages = {329-333}, pmid = {19344084}, issn = {1592-7830}, mesh = {Adult ; Aged ; *Agriculture ; Asbestos/*adverse effects ; Asbestosis/diagnosis/epidemiology/etiology ; *Carcinogens ; Carcinoma, Squamous Cell/diagnosis/epidemiology/etiology ; Conservation of Natural Resources ; Environmental Exposure/*adverse effects ; Female ; Humans ; Italy/epidemiology ; Lung Neoplasms/diagnosis/epidemiology/etiology ; Male ; Mesothelioma/diagnosis/epidemiology/etiology ; Middle Aged ; Pleural Neoplasms/diagnosis/epidemiology/etiology ; Registries ; Retrospective Studies ; Textile Industry ; }, abstract = {During the last four years, a deeper examination of malignant mesothelioma (MM) cases occurred within non asbestos textile industry highlighted asbestos past exposure in several textile industrial divisions. In spite of that, poor information about recycled textile bags previously containing asbestos fibres is available to the National Mesothelioma Registry, although holding a remarkable data bank on more than 3500 work histories and sources of asbestos exposures. Besides the analysis of the exposure circumstances and the registered health effects of the past exposure within the recycling activity, the aim of this research was to relate the possible involvement of the agricultural sector, where the use of recycled jute bags was very diffused. The MM cases were collected from the Mesothelioma Registry of Brescia, asbestosis, pleural plaques and lung cancer cases were collected from the Occupational Diseases Archive of the Local Public Occupational Health Service of the Province of Brescia. During the 1977-2006 period, 8 cases of MM, 4 cases of pulmonary asbestosis, 4 of isolated bilateral pleural plaques and I of lung cancer in pulmonary asbestosis, were observed among workers employed in bags recycling activity in 4 small companies, one of them still operating, employing about 50 workers. Even more, among the 65 MM cases classified by the Registry with "unknown asbestos exposure" (UAE), the most relevant frequency of working histories concerned the agriculture sector. Confirming a past signalling, the investigations underlined the cross linkage between this working activity and the diffusion of recycled bags in the agriculture sector. In the Province of Brescia, the activities of these small jute bags recycling plants were linked, even geographically, to the asbestos cement manufacture plant using a huge number of bags, roughly until mid seventies. Therefore, a large number of these recycled bags, previously containing asbestos, were generally used for harvesting and trading agricultural typical products of northern Italy. According to the 2003 National Mesothelioma Registry Guide Lines, MM in agricultural workers are still classified as UAE due to poor information available. In the light of these new findings, it looks reasonable to review the UAE within agriculturalists attributing a new classification of "possible" occupational asbestos exposure, although other exposure circumstances might have occurred in the past.}, } @article {pmid19344083, year = {2008}, author = {Spigno, F and Gentile, R and Valente, T and Capannelli, G}, title = {[Diagnosis in related pathologic asbestosis, clinical case of a suspected occupational neoplasm].}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {30}, number = {4}, pages = {324-328}, pmid = {19344083}, issn = {1592-7830}, mesh = {Aged ; Asbestosis/complications/diagnosis/*pathology/surgery ; Diagnosis, Differential ; Humans ; Lung Neoplasms/diagnosis/etiology/*pathology/surgery ; Male ; Occupational Exposure/*adverse effects ; Solitary Pulmonary Nodule/diagnosis/etiology/*pathology/surgery ; Treatment Outcome ; }, abstract = {In our country the rate of asbestos-related neoplasia, in particular pleural mesothelioma and lung cancer, is increasing; the data provided by INAIL concerning the complaints for occupational diseases filed in 2006 ex table D.P.R. 336/1994 (neoplastic diseases caused by asbestos: pleural, pericardial and peritoneal mesothelioma; lung cancer) are significant. The total number of such complaints in our country amounts to 753 (135 in Liguria and 384 in the north-western regions). As the issue of health following up of former exposed workers is actually an important concern of occupational medicine, some protocols have recently been proposed with the aim to early diagnose asbestos related neoplasia, thus getting a better prognosis. Under the medico-legal aspect, the need for fixing the proper criteria for aetiological attribution to asbestos of lung cancer in subjects previously exposed to that substance is a controversial issue, being the various approaches quite different; the incidental finding of a lung "coin lesion" in a subject who had been holding an annuity for years, as an indemnity granted by INAIL for asbestosis, has prompted the authors both to go over such a clinical case and to review the literature on the topic, in particular as to the complex medico-legal implications.}, } @article {pmid19321410, year = {2009}, author = {Chen, JL and Hsu, YH}, title = {Malignant mesothelioma of the tunica vaginalis testis: a case report and literature review.}, journal = {The Kaohsiung journal of medical sciences}, volume = {25}, number = {2}, pages = {77-81}, doi = {10.1016/S1607-551X(09)70044-0}, pmid = {19321410}, issn = {1607-551X}, mesh = {Aged ; Humans ; Male ; Mesothelioma/mortality/*pathology/surgery ; Testicular Neoplasms/mortality/*pathology/surgery ; }, abstract = {Malignant mesothelioma of the tunica vaginalis testis is a rare but often fatal malignancy. Here, we report one patient with locally advanced disease who has a history of asbestos exposure. We review the literature concerning current management strategies of the disease. Radical surgery plus adjuvant radiotherapy seems to provide the best results.}, } @article {pmid19304273, year = {2009}, author = {Kamp, DW}, title = {Asbestos-induced lung diseases: an update.}, journal = {Translational research : the journal of laboratory and clinical medicine}, volume = {153}, number = {4}, pages = {143-152}, pmid = {19304273}, issn = {1931-5244}, support = {R01 ES013995/ES/NIEHS NIH HHS/United States ; R01 ES013995-01A1/ES/NIEHS NIH HHS/United States ; R01 HL035440/HL/NHLBI NIH HHS/United States ; R01 HL035440-21/HL/NHLBI NIH HHS/United States ; }, mesh = {Asbestos/*toxicity ; Humans ; Lung Diseases/*chemically induced/epidemiology/physiopathology ; }, abstract = {Asbestos causes asbestosis (pulmonary fibrosis caused by asbestos inhalation) and malignancies (bronchogenic carcinoma and mesothelioma) by mechanisms that are not fully elucidated. Despite a dramatic reduction in asbestos use worldwide, asbestos-induced lung diseases remain a substantial health concern primarily because of the vast amounts of fibers that have been mined, processed, and used during the 20th century combined with the long latency period of up to 40 years between exposure and disease presentation. This review summarizes the important new epidemiologic and pathogenic information that has emerged over the past several years. Whereas the development of asbestosis is directly associated with the magnitude and duration of asbestos exposure, the development of a malignant clone of cells can occur in the setting of low-level asbestos exposure. Emphasis is placed on the recent epidemiologic investigations that explore the malignancy risk that occurs from nonoccupational, environmental asbestos exposure. Accumulating studies are shedding light on novel mechanistic pathways by which asbestos damages the lung. Attention is focused on the importance of alveolar epithelial cell (AEC) injury and repair, the role of iron-derived reactive oxygen species (ROS), and apoptosis by the p53- and mitochondria-regulated death pathways. Furthermore, recent evidence underscores crucial roles for specific cellular signaling pathways that regulate the production of cytokines and growth factors. An evolving role for epithelial-mesenchymal transition (EMT) is also reviewed. The translational significance of these studies is evident in providing the molecular basis for developing novel therapeutic strategies for asbestos-related lung diseases and, importantly, other pulmonary diseases, such as interstitial pulmonary fibrosis and lung cancer.}, } @article {pmid19302997, year = {2009}, author = {Grigoriu, B and Chahine, B and Zerimech, F and Grégoire, M and Balduyck, M and Copin, MC and Devos, P and Lassalle, P and Scherpereel, A}, title = {Serum mesothelin has a higher diagnostic utility than hyaluronic acid in malignant mesothelioma.}, journal = {Clinical biochemistry}, volume = {42}, number = {10-11}, pages = {1046-1050}, doi = {10.1016/j.clinbiochem.2009.03.007}, pmid = {19302997}, issn = {1873-2933}, mesh = {Aged ; Female ; GPI-Linked Proteins ; Humans ; Hyaluronic Acid/*blood ; Male ; Membrane Glycoproteins/*blood ; Mesothelin ; Mesothelioma/*blood/*diagnosis ; Pleural Effusion/blood ; }, abstract = {UNLABELLED: We assessed comparatively the diagnostic value of two potential malignant pleural mesothelioma (MPM) markers: hyaluronic acid (HA) and soluble mesothelin.

MATERIALS AND METHOD: We measured serum and pleural fluid values of mesothelin and hyaluronic acid in 76 patients with MPM, 33 patients with pleural metastases of carcinomas (Mets group) and 27 patients with benign pleural effusion related to asbestos exposure (BPLAE).

RESULTS: Using a serum HA cut-off of 100 microg/L, 8 patients/33 (24.2%) were positive in the Mets group versus 20/76 (26.3%) in the MPM group and only 1/27 BPLAE patients. The area under ROC curve for serum HA in MPM versus Mets or BPLAE groups was only 0.617 while it was 0.755 for mesothelin. In pleural fluid, both markers had similar diagnostic values.

CONCLUSIONS: Serum mesothelin is more sensitive than hyaluronic acid in diagnosing MPM and there is no benefit in combining both markers.}, } @article {pmid19301253, year = {2009}, author = {Arora, VK and Aggarwal, S and Mathur, S and Rath, GK and Julka, PK}, title = {Pleural mesothelioma: an unusual case diagnosed on pleural fluid cytology and immunocytochemistry.}, journal = {Diagnostic cytopathology}, volume = {37}, number = {7}, pages = {509-512}, doi = {10.1002/dc.21063}, pmid = {19301253}, issn = {1097-0339}, mesh = {Adult ; Diagnosis, Differential ; Humans ; Immunohistochemistry ; Male ; Mesothelioma/diagnosis/diagnostic imaging/*pathology ; Pleural Effusion, Malignant/diagnostic imaging/*pathology ; Sentinel Lymph Node Biopsy ; Ultrasonography, Doppler, Color ; Venous Thrombosis/diagnostic imaging/pathology ; }, abstract = {Mesothelioma is a rare neoplasm with relationship to occupational and environmental exposure to asbestos. Its accurate and early diagnosis is often difficult. We present an unusual clinical presentation and diagnostic dilemma in a 30-year-male, who presented with neck pain and diffuse edema of left upper limb. The color Doppler ultrasound revealed venous thrombosis. The right supraclavicular lymph node biopsy revealed a poorly differentiated carcinoma. The patient had mild bilateral pleural effusion, the characteristic cytomorphological features of mesothelioma on fluid cytology were helpful in establishing the diagnosis.}, } @article {pmid19285954, year = {2009}, author = {Ivanov, SV and Ivanova, AV and Goparaju, CM and Chen, Y and Beck, A and Pass, HI}, title = {Tumorigenic properties of alternative osteopontin isoforms in mesothelioma.}, journal = {Biochemical and biophysical research communications}, volume = {382}, number = {3}, pages = {514-518}, doi = {10.1016/j.bbrc.2009.03.042}, pmid = {19285954}, issn = {1090-2104}, mesh = {Alternative Splicing ; Amino Acid Sequence ; Cell Line, Tumor ; Cell Transformation, Neoplastic/genetics/*metabolism ; Humans ; Mesothelioma/*metabolism/pathology ; Molecular Sequence Data ; Osteopontin/genetics/*physiology ; Pleura/metabolism/pathology ; Protein Isoforms/genetics/physiology ; RNA, Messenger/metabolism ; Solitary Fibrous Tumor, Pleural/*metabolism/pathology ; Up-Regulation ; }, abstract = {Osteopontin (SPP1) is an inflammatory cytokine that we previously characterized as a diagnostic marker in patients with asbestos-induced malignant mesothelioma (MM). While SPP1 shows both pro- and anti-tumorigenic biological effects, little is known about the molecular basis of these activities. In this study, we demonstrate that while healthy pleura possesses all three differentially spliced SPP1 isoforms (A-C), in clinical MM specimens isoform A is markedly up-regulated and predominant. To provide a clue to possible functions of the SPP1 isoforms we next performed their functional evaluation via transient expression in MM cell lines. As a result, we report that isoforms A-C demonstrate different activities in cell proliferation, wound closure, and invasion assays. These findings suggest different functions for SPP1 isoforms and underline pro-tumorigenic properties of isoforms A and B.}, } @article {pmid19282317, year = {2009}, author = {Loomis, D and Dement, JM and Wolf, SH and Richardson, DB}, title = {Lung cancer mortality and fibre exposures among North Carolina asbestos textile workers.}, journal = {Occupational and environmental medicine}, volume = {66}, number = {8}, pages = {535-542}, doi = {10.1136/oem.2008.044362}, pmid = {19282317}, issn = {1470-7926}, support = {R01-OH007803/OH/NIOSH CDC HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asbestos, Serpentine/*toxicity ; Asbestosis/*mortality ; Cohort Studies ; Female ; Humans ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; Middle Aged ; Mineral Fibers/toxicity ; North Carolina/epidemiology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*mortality ; Textile Industry ; Young Adult ; }, abstract = {OBJECTIVE: To describe mortality among workers exposed to chrysotile asbestos and evaluate the relationship between lung cancer and asbestos fibre exposure.

METHODS: Workers employed for at least 1 day between 1 January 1950 and 31 December 1973 in any of four plants in North Carolina, USA that produced asbestos textile products were enumerated. Vital status was ascertained through 31 December 2003. Historical exposures to asbestos fibres were estimated from work histories and 3578 industrial hygiene measurements taken in 1935-1986. Mortality of the cohort was compared with that of the national population via standardised mortality ratios (SMRs). Exposure-response relationships for lung cancer were examined within the cohort using Poisson regression to compute adjusted mortality rate ratios.

RESULTS: Follow-up of 5770 workers included in the cohort resulted in 181 640 person-years of observation, with 2583 deaths from all causes and 277 from lung cancer. Mortality from all causes, all cancers and lung cancer was significant higher than expected, with SMRs of 1.47 for all causes, 1.41 for all cancer and 1.96 (95% CI 1.73 to 2.20) for lung cancer. SMRs for pleural cancer, mesothelioma and pneumoconiosis were also elevated. The risk of lung cancer and asbestosis increased with cumulative fibre exposure (RR 1.102 per 100 fibre-year/ml, 95% CI 1.044 to 1.164, and RR 1.249 per 100 fibre-year/ml, 95% CI 1.186 to 1.316, respectively, for total career exposure).

CONCLUSIONS: This study provides further evidence that exposure to chrysotile asbestos in textile manufacturing is associated with increased risk of lung cancer, asbestosis cancer of the pleura and mesothelioma.}, } @article {pmid19267128, year = {2009}, author = {Pezerat, H}, title = {Chrysotile biopersistence: the misuse of biased studies.}, journal = {International journal of occupational and environmental health}, volume = {15}, number = {1}, pages = {102-106}, doi = {10.1179/107735209799449770}, pmid = {19267128}, issn = {1077-3525}, mesh = {Animals ; Asbestos, Serpentine/chemistry/*pharmacokinetics/poisoning ; Bias ; Biological Availability ; Chemical Industry/standards ; Communication ; Environmental Exposure/adverse effects ; Humans ; Lung/metabolism ; Lung Neoplasms/*etiology/metabolism ; Mesothelioma/*etiology/metabolism ; Occupational Exposure/adverse effects ; }, abstract = {Although it is widely accepted that exposure to any asbestos type can increase the likelihood of lung cancer, mesothelioma, and non-malignant lung and pleural disorders, manufacturers and some chrysotile miners' unions contend that chrysotile either does not cause disease or that there is insufficient evidence to reach a conclusion. At the same time, Dr. D.M. Bernstein has published several animal studies, financed by the Québec Chrysotile Institute, to determine chrysotile biopersistence in the lungs. Bernstein's study protocol induces a very short fiber half-life, from which he concludes weak chrysotile carcinogenicity. Bernstein's findings contradict results obtained by independent scientists. Bernstein's results can only be explained by an aggressive pre-treatment of fibers, inducing many faults and fragility in the fibers' structure, leading to rapid hydration and breaking of long fibers in the lungs.}, } @article {pmid19263869, year = {2009}, author = {Barbieri, PG and Somigliana, A and Lombardi, S and Girelli, R and Benvenuti, A}, title = {[Asbestos fibre lung burden and exposure indices in asbestos-cement workers].}, journal = {La Medicina del lavoro}, volume = {100}, number = {1}, pages = {21-28}, pmid = {19263869}, issn = {0025-7818}, mesh = {Aged ; Asbestos, Amosite/adverse effects/*analysis ; Asbestos, Crocidolite/adverse effects/*analysis ; Asbestosis/etiology/metabolism/pathology ; Construction Materials/*adverse effects ; Electron Probe Microanalysis ; Fibrosis ; Humans ; Italy ; Lung/*chemistry ; Lung Neoplasms/chemistry/etiology/ultrastructure ; Male ; Mesothelioma/chemistry/etiology/ultrastructure ; Microscopy, Electron, Scanning ; Middle Aged ; Mineral Fibers/adverse effects ; Occupational Diseases/*etiology/metabolism/pathology ; Occupational Exposure/*classification ; Occupations ; Pleura/chemistry/ultrastructure ; Pleural Neoplasms/chemistry/etiology/ultrastructure ; }, abstract = {BACKGROUND: In many previous studies, the asbestos fibres retained in the lung were regarded as a good index of cumulative occupational asbestos exposure. Twelve workers suffering from asbestos-related diseases and had been employed in an asbestos-cement factory operating from 1961 to 1994 underwent post mortem investigations in the course of a criminal law suit.

OBJECTIVES: Samples of lung tissues were collected for electron microscopy analysis to measure the asbestos fibre burden of the lungs in workers with high exposure, and assess the possible correlation between asbestos fibre lung burden and the estimated levels of cumulative exposure.

METHODS: Samples of lung parenchyma obtained from a consecutive series of 12 post-mortem examinations that were performed between 1994 and 2007and included 5 cases of malignant pleural mesothelioma, 4 lung cancers, 1 case of asbestosis and2 ofpleuralplagues, were collected, stored and analysed by SEM electron microscopy, according to the methods suggested by the current scientific literature. For each worker, all males, a detailed occupational history was reconstructed by means ofpersonal interviews; both the measurements of airborne asbestos fibresperformed by the factory in the 1970's and the duration of each single job in the plant were taken into account to estimate an individual cumulative exposure index.

RESULTS: A wide variation of total asbestos fibre concentrations in the lung (1,320-118 million) was observed; in all 12 workers, the lung amphibole fibre burden exceeded 1,000,000 fibres per g/dry tissue, The highest values were detected in the mesothelioma cases, in which the mean fibre concentrations differed statistically (t=2.29, p=0.045) from the mean calculated for the other asbestos-related diseases; in 9 subjects only amphibole fibres were detected. There was a good correlation between total asbestos fibre concentration and cumulative exposure index (r=0.91, p<0.0001).

CONCLUSION: This study, which was numerically the biggest ever performed in Italy for this category of workers, confirms a wide range of total asbestos fibre burden in heavily occupationally exposed workers and showed that of the asbestos-related diseases, the highest lung concentrations of asbestos fibres were reached in cases of mesothelioma. It was also observed that almost the entire lung burden consists of only amphibole fibres, all exceeding 1 million per gramme of dry tissue. This study tested a synthetic cumulative occupational exposure index, which appears to be well correlated to the level of exposure established by biological analysis.}, } @article {pmid19263868, year = {2009}, author = {Paoletti, L and Bruni, BM}, title = {[Size distribution of amphibole fibres from lung and pleural tissues sampled from mesothelioma cases due to environmental exposure].}, journal = {La Medicina del lavoro}, volume = {100}, number = {1}, pages = {11-20}, pmid = {19263868}, issn = {0025-7818}, mesh = {Aged ; Aged, 80 and over ; Asbestos, Amphibole/adverse effects/*analysis/chemistry/isolation & purification ; Asbestosis/etiology/pathology ; Environmental Exposure ; Female ; Humans ; Lung/chemistry/ultrastructure ; Lung Neoplasms/chemistry/etiology/*ultrastructure ; Male ; Mesothelioma/chemistry/etiology/*ultrastructure ; Microscopy, Electron, Scanning ; Middle Aged ; Mineral Fibers/adverse effects/analysis/classification ; Models, Biological ; Particle Size ; Pleural Neoplasms/chemistry/etiology/*ultrastructure ; Soil/analysis ; }, abstract = {BACKGROUND: It has been suggested that malignant mesothelioma might be mainly or only connected with the action of short and ultrathin fibres. On the basis of this hypothesis fibres less than 5 microm long and 0.2-0.1 microm thick would enter the pulmonary-pleura barrier and reach the parietal pleura thus inducing mesothelioma. The hypothesis raised a stimulating scientific discussion.

OBJECTIVES: The aim of this communication is to report the initial results obtained comparing the size of amphibole fibres from healthy lung tissue with those from pleural tissue sampled from subjects whose death cause of death was mesothelioma.

METHODS: Four mesothelioma cases due to environmental exposure were studied; the fibres were categorized by scanning electron microscopy; for every fibre, length and diameter were measured and the mineral type was defined by its chemical composition determined by X-ray microanalysis.

RESULTS: The most important characteristics of the detected fibres were: the average length offibres from the lung and pleural tissues taken from the same subject did not difer, in all cases, by more than 10-12%; 95% offibres found in the lung tissues of all subjects had a length greater than 5 microm; 98% of fibres found in the pleural tissues had a length greater than 5 microm; the average diameter of the fibres found in the pleural tissues was 70% of the diameter of the fibres from the lung tissues.

CONCLUSIONS: The experimental data obtained in this study confirm the correlation between malignant mesothelioma and the presence in the lung and pleural tissues of fibres with a length greater, even much greater, than 4-5 microm; thus the hypothesis that the chief factors inducing mesothelioma are the "ultrashort" and "ultrathin" fibres appears rather weak.}, } @article {pmid19260532, year = {2009}, author = {Nojiri, S and Yumino, Y and Sato, K and Onodera, R and Nakayama, K and Kuwano, K}, title = {[A case of pericardial malignant mesothelioma accompanied by primary lung adenocarcinoma].}, journal = {Nihon Kokyuki Gakkai zasshi = the journal of the Japanese Respiratory Society}, volume = {47}, number = {2}, pages = {104-109}, pmid = {19260532}, issn = {1343-3490}, mesh = {Adenocarcinoma/*pathology ; Asbestosis/pathology ; Heart Neoplasms/*pathology ; Humans ; Lung Neoplasms/*pathology ; Male ; Mesothelioma/*pathology ; Middle Aged ; Neoplasms, Multiple Primary/*pathology ; *Pericardium ; }, abstract = {A 63-year-old man was admitted to Jikei University Hospital, with anasarca, and dyspnea in May, 2004. Echocardiograms and CT scans showed massive pericardial effusion, nodules on the pericardium and a tumor in the lower lobe of the left lung. Pathological examination of the punctured pericardial effusions yielded a diagnosis of pericardial malignant mesothelioma. However, no pathogen or malignant cells were identified from multiple biopsy specimens of the lung tumor, which were obtained by brochoscopic techniques. Since he worked as a fisherman in a diesel-powered fishing boat, he was possibly exposed to asbestos. On autopsy, the lung tumor was diagnosed as a primary lung adenocaricinoma. Exposure to asbestos is an important risk factor for both mesothelioma and lung cancer. However, pericardial malignant mesothelioma in itself is rare among mesothelioma. This is only the second report of malignant mesothelioma with primary lung adenocarcinoma, to date.}, } @article {pmid19259084, year = {2009}, author = {Rake, C and Gilham, C and Hatch, J and Darnton, A and Hodgson, J and Peto, J}, title = {Occupational, domestic and environmental mesothelioma risks in the British population: a case-control study.}, journal = {British journal of cancer}, volume = {100}, number = {7}, pages = {1175-1183}, pmid = {19259084}, issn = {1532-1827}, support = {//Cancer Research UK/United Kingdom ; }, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Asbestos, Amosite/adverse effects ; Case-Control Studies ; Environmental Exposure/*adverse effects ; Female ; Humans ; Male ; Mesothelioma/*etiology/mortality ; Middle Aged ; Occupational Exposure/*adverse effects ; Odds Ratio ; Risk ; }, abstract = {We obtained lifetime occupational and residential histories by telephone interview with 622 mesothelioma patients (512 men, 110 women) and 1420 population controls. Odds ratios (ORs) were converted to lifetime risk (LR) estimates for Britons born in the 1940s. Male ORs (95% confidence interval (CI)) relative to low-risk occupations for >10 years of exposure before the age of 30 years were 50.0 (25.8-96.8) for carpenters (LR 1 in 17), 17.1 (10.3-28.3) for plumbers, electricians and painters, 7.0 (3.2-15.2) for other construction workers, 15.3 (9.0-26.2) for other recognised high-risk occupations and 5.2 (3.1-8.5) in other industries where asbestos may be encountered. The LR was similar in apparently unexposed men and women (approximately 1 in 1000), and this was approximately doubled in exposed workers' relatives (OR 2.0, 95% CI 1.3-3.2). No other environmental hazards were identified. In all, 14% of male and 62% of female cases were not attributable to occupational or domestic asbestos exposure. Approximately half of the male cases were construction workers, and only four had worked for more than 5 years in asbestos product manufacture.}, } @article {pmid19254909, year = {2009}, author = {Harding, AH and Darnton, A and Wegerdt, J and McElvenny, D}, title = {Mortality among British asbestos workers undergoing regular medical examinations (1971-2005).}, journal = {Occupational and environmental medicine}, volume = {66}, number = {7}, pages = {487-495}, doi = {10.1136/oem.2008.043414}, pmid = {19254909}, issn = {1470-7926}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Asbestosis/mortality ; Cardiovascular Diseases/mortality ; Cause of Death ; Cohort Studies ; Female ; Humans ; Male ; Middle Aged ; Neoplasms/*mortality ; Occupational Diseases/*mortality ; Occupational Exposure/*adverse effects ; Physical Examination ; Regression Analysis ; United Kingdom/epidemiology ; Young Adult ; }, abstract = {OBJECTIVES: The Great Britain Asbestos Survey was established to monitor mortality among workers covered by regulations to control occupational exposure to asbestos. This study updates the estimated burden of asbestos-related mortality in the cohort, and identifies risk factors associated with mortality.

METHODS: From 1971, workers were recruited during initially voluntary and later statutory medical examinations. A brief questionnaire was completed during the medical, and participants were flagged for death registrations. Standardised mortality ratios (SMRs) and proportional mortality ratios (PMRs) were calculated for deaths occurring before 2006. Poisson regression analyses were undertaken for diseases with significant excess mortality.

RESULTS: There were 15 496 deaths among 98 117 workers followed-up for 1 779 580 person-years. The SMR for all cause mortality was 141 (95% CI 139 to 143) and for all malignant neoplasms 163 (95% CI 159 to 167). The SMRs for cancers of the stomach (166), lung (187), peritoneum (3730) and pleura (968), mesothelioma (513), cerebrovascular disease (164) and asbestosis (5594) were statistically significantly elevated, as were the corresponding PMRs. In age and sex adjusted analysis, birth cohort, age at first exposure, year of first exposure, duration of exposure, latency and job type were associated with the relative risk of lung, pleural and peritoneal cancers, asbestosis and mesothelioma mortality.

CONCLUSIONS: Known associations between asbestos exposure and mortality from lung, peritoneal and pleural cancers, mesothelioma and asbestosis were confirmed, and evidence of associations with stroke and stomach cancer mortality was observed. Limited evidence suggested that asbestos-related disease risk may be lower among those first exposed in more recent times.}, } @article {pmid19251786, year = {2009}, author = {Jackaman, C and Cornwall, S and Lew, AM and Zhan, Y and Robinson, BW and Nelson, DJ}, title = {Local effector failure in mesothelioma is not mediated by CD4+ CD25+ T-regulator cells.}, journal = {The European respiratory journal}, volume = {34}, number = {1}, pages = {162-175}, doi = {10.1183/09031936.00101008}, pmid = {19251786}, issn = {1399-3003}, mesh = {Animals ; CD4-Positive T-Lymphocytes/immunology/*metabolism ; Cell Line, Tumor ; Female ; GPI-Linked Proteins ; Immunotherapy/methods ; Interleukin-2/metabolism ; Interleukin-2 Receptor alpha Subunit/*biosynthesis ; Interleukins/metabolism ; Membrane Glycoproteins/metabolism ; Mesothelin ; Mesothelioma/*blood/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Models, Biological ; T-Lymphocytes, Regulatory/immunology/*metabolism ; }, abstract = {The aim of the present study was to define the point at which mesothelioma T-cell responses fail in order to design better immunotherapies. A murine model of mesothelioma was used which was established with asbestos. Inoculation of tumour cells into syngeneic mice results in progressing tumours with similar histopathology to human mesothelioma. The tumour cells secrete a marker tumour antigen similar to secreted tumour-associated products, such as mesothelin. The mesothelioma microenvironment contains stromal elements including dendritic cells, effector CD8(+) and CD4(+) T-cells, and CD4(+) T-regulatory (Tregs) cells, all of which are activated in situ, implying chronic inflammation. Tumour antigens are rapidly transported to draining lymph nodes wherein tumour-specific T-cell responses are generated. Despite the generation of potent CD8(+) cytotoxic lymphocyte in lymphoid organs, those that infiltrate tumours cannot restrain tumour growth suggesting local suppression. Splenic Tregs did not suppress protective responses in adoptive transfer experiments suggesting that systemic Tregs play little role in regulating anti-mesothelioma immune responses. Finally, removal of CD25(+) Tregs from the tumour site and lymphoid organs did not alter tumour growth with or without interleukin (IL)-2 or IL-21 immunotherapy. Tregs are not potent regulators of anti-mesothelioma immunity and targeting these cells may not improve results.}, } @article {pmid19248380, year = {2009}, author = {Oxtoby, K}, title = {The lethal legacy of asbestos.}, journal = {Nursing times}, volume = {105}, number = {3}, pages = {34-36}, pmid = {19248380}, issn = {0954-7762}, mesh = {Asbestos/*adverse effects ; Building Codes ; Compensation and Redress ; Hospital Design and Construction ; Humans ; Mesothelioma/*etiology/mortality ; *Nursing Staff, Hospital ; Occupational Exposure/*adverse effects ; Occupational Health ; United Kingdom/epidemiology ; }, } @article {pmid19241668, year = {2008}, author = {Pérez-Guzmán, C and Vargas, MH and Torre-Bouscoulet, L}, title = {[Pleural mesothelioma in a Mexican population: clinical and radiological similarities among histopathologic patterns].}, journal = {Revista medica del Instituto Mexicano del Seguro Social}, volume = {46}, number = {5}, pages = {561-566}, pmid = {19241668}, issn = {0443-5117}, mesh = {Female ; Humans ; Male ; Mesothelioma/*diagnosis/diagnostic imaging/pathology ; Mexico ; Middle Aged ; Pleural Neoplasms/*diagnosis/diagnostic imaging/pathology ; Radiography ; }, abstract = {OBJECTIVE: To describe clinical and radiological features of patients with pleural mesothelioma, according to main histological types.

METHODS: Clinical records of inpatients admitted with diagnosis of pleural mesothelioma to the Instituto Nacional de Enfermedades Respiratorias in the last 11 years, were reviewed.

RESULTS: We analyzed 85 cases confirmed by immunohistochemistry. The most frequent histological type was epithelial (84.7 %), followed by sarcomatous (12.9 %) and mixed (2.4 %) types. Comparison between epithelial and sarcomatous types showed no differences in age (53.7 +/- 13.1 vs. 55.9 +/- 11.0 years, respectively), male : female ratio (2.3 : 1 vs. 1.8 : 1), history of asbestos exposure (34.7 vs. 27.2 %), tobacco habit (54.2 vs 45.4 %), occupation, evolution time (4.8 +/- 3.3 vs. 4.4 +/- 3.7 months), pain, dyspnea and cough, right-side predominance (55.6 vs. 81.8 %), radiological image with pleural effusion (59.7 vs. 36.4 %) or pleural thickening (38.9 vs. 63.6 %), and diagnostic efficiency of closed pleural biopsy (58.3 vs. 27.2 %).

CONCLUSIONS: Our results suggest that clinical and radiological features of epithelial and sarcomatous histological types are very similar. Additionally, we found a high frequency of epithelial mesothelioma, which contrasts with findings from other countries, suggesting that the type of asbestos or other factors involved in the development of pleural mesothelioma differ from those existing in other regions of the world.}, } @article {pmid19236184, year = {2009}, author = {Bertino, P and Carbone, M and Pass, H}, title = {Chemotherapy of malignant pleural mesothelioma.}, journal = {Expert opinion on pharmacotherapy}, volume = {10}, number = {1}, pages = {99-107}, doi = {10.1517/14656560802631285}, pmid = {19236184}, issn = {1744-7666}, mesh = {Antineoplastic Combined Chemotherapy Protocols/administration & dosage/*therapeutic use ; Asbestos/toxicity ; Clinical Trials, Phase III as Topic ; Combined Modality Therapy ; Disease-Free Survival ; Humans ; Mesothelioma/chemically induced/*drug therapy/mortality ; Palliative Care ; Pleural Neoplasms/chemically induced/*drug therapy/mortality ; Randomized Controlled Trials as Topic ; }, abstract = {BACKGROUND: Owing to worldwide use of asbestos during the past century, the global incidence of mesothelioma is still increasing. Although the outcome for patients remains poor, there has been definite progress in the systemic treatment of this disease within the past 5 years.

OBJECTIVE: By examining the clinical trials performed and the role of novel emerging agents, this review aims to provide an 'expert opinion' on evidences that validate chemotherapy as current 'standard of care' for inoperable mesothelioma.

METHODS: Relevant literature about clinical trials was reviewed using a PubMed search and other relevant data about novel therapeutic approaches both established and in development.

CONCLUSION: The response rates achieved using chemotherapeutic treatments are higher than previous ones, and in the future may be improved by the use of combined and personalized therapies.}, } @article {pmid19234654, year = {2009}, author = {Chua, TC and Yan, TD and Morris, DL}, title = {Surgical biology for the clinician: peritoneal mesothelioma: current understanding and management.}, journal = {Canadian journal of surgery. Journal canadien de chirurgie}, volume = {52}, number = {1}, pages = {59-64}, pmid = {19234654}, issn = {1488-2310}, mesh = {Asbestos/adverse effects ; Biomarkers, Tumor ; Chemotherapy, Cancer, Regional Perfusion ; Diagnostic Imaging ; Endoscopy, Gastrointestinal ; Humans ; Hyperthermia, Induced ; Mesothelioma/*diagnosis/etiology/*therapy ; Peritoneal Neoplasms/*diagnosis/etiology/*therapy ; }, abstract = {Mesothelioma is an asbestos-related tumour. Mesothelioma in the thorax occurs on the pleura and is known as pleural mesothelioma. It is the more common form of mesothelioma, accounting for 70% of cases. The other form occurs in the abdomen. It accounts for much of the remaining 30% and is known as peritoneal mesothelioma. Early diagnosis of peritoneal mesothelioma is often difficult because the early symptoms are often overlooked as being a benign ailment of the gastrointestinal tract. Therefore, diagnosis often occurs at an advanced stage when disease is widespread throughout the peritoneal cavity. Treatment approaches have evolved in the last decade from systemic chemotherapy and palliative surgery to aggressive cytoreductive surgery and perioperative intraperitoneal chemotherapy. This has led to a marked increase in survival among patients who were once classified as "preterminal." We update on the current understanding of peritoneal mesothelioma from a clinical perspective in hope that greater clinician awareness will promote best practice management of this condition.}, } @article {pmid19234144, year = {2009}, author = {De Bruin, ML and Burgers, JA and Baas, P and van 't Veer, MB and Noordijk, EM and Louwman, MW and Zijlstra, JM and van den Berg, H and Aleman, BM and van Leeuwen, FE}, title = {Malignant mesothelioma after radiation treatment for Hodgkin lymphoma.}, journal = {Blood}, volume = {113}, number = {16}, pages = {3679-3681}, doi = {10.1182/blood-2008-10-184705}, pmid = {19234144}, issn = {1528-0020}, mesh = {Adult ; Aged ; Disease-Free Survival ; Female ; Follow-Up Studies ; Hodgkin Disease/*mortality/*radiotherapy ; Humans ; Male ; Mesothelioma/diagnosis/*mortality ; Middle Aged ; Neoplasms, Radiation-Induced/diagnosis/*mortality ; Retrospective Studies ; Risk Factors ; Sex Factors ; Survival Rate ; }, abstract = {Malignant mesothelioma is a relatively uncommon malignancy. Although the pathogenesis is primarily related to asbestos, the disease may be associated with radiation exposure. Recently, increased risks for second primary mesothelioma after radiation for lymphoma have been reported. Because these findings are based on small numbers of patients, they need to be confirmed. We examined mesothelioma risk in 2567 5-year survivors of Hodgkin lymphoma. The risk was almost 30-fold increased in Hodgkin lymphoma patients treated with irradiation compared with the general population. Although histology and survival of the mesothelioma cases were comparable with cases from the general population, asbestos exposure and the proportion of males were lower than expected. The evidence for radiotherapy as cause for mesothelioma independent of exposure to asbestos is expanding, and the diagnosis of mesothelioma should be kept in mind whenever related symptoms arise in patients who had previous irradiation.}, } @article {pmid19233506, year = {2009}, author = {Amatori, S and Papalini, F and Lazzarini, R and Donati, B and Bagaloni, I and Rippo, MR and Procopio, A and Pelicci, PG and Catalano, A and Fanelli, M}, title = {Decitabine, differently from DNMT1 silencing, exerts its antiproliferative activity through p21 upregulation in malignant pleural mesothelioma (MPM) cells.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {66}, number = {2}, pages = {184-190}, doi = {10.1016/j.lungcan.2009.01.015}, pmid = {19233506}, issn = {1872-8332}, mesh = {Antimetabolites, Antineoplastic/*pharmacology ; Azacitidine/*analogs & derivatives/pharmacology ; Cell Cycle/drug effects ; Cell Survival/drug effects ; Cyclin-Dependent Kinase Inhibitor p21/*metabolism ; DNA (Cytosine-5-)-Methyltransferase 1 ; DNA (Cytosine-5-)-Methyltransferases/*antagonists & inhibitors/genetics ; DNA Methylation/drug effects ; Decitabine ; Gene Silencing ; Humans ; Neoplasms, Mesothelial/genetics/*metabolism ; Pleural Neoplasms/genetics/*metabolism ; Up-Regulation/*drug effects ; }, abstract = {Malignant pleural mesothelioma (MPM) is a locally aggressive neoplasm, principally linked to asbestos fibres exposure. Strong evidences associate this pollutant with induction of DNA breaks, aberrant chromosomes segregation and important chromosomal rearrangements, considered crucial events in malignant transformation. A considerable contribution to cellular transformation in MPM is also given by the presence of high genomic instability, as well as by the increased DNA methylation, and consequent decreased expression, of tumor-suppressor genes. In this study we first demonstrated that MPM cells are characterized by a decreased methylation level of pericentromeric DNA sequences which can justify, at least in part, the genomic instability observed in this neoplasia. Concomitantly, we found a paradoxical increased expression of DNMT1, the most expressed DNA methyltransferases in MPM cells, DNMT3a and all five isoforms of DNMT3b. Thus, we compared two experimental strategies, DNMT1 silencing and usage of a demethylating agent (5-aza-2'-deoxycytidine or Decitabine), both theoretically able to revert the locally hypermethylated phenotype and considered potential future therapeutic approaches for MPM. Interestingly, both strategies substantially decrease cell survival of MPM cells but the antitumor activity of Decitabine, differently from DNMT1 silencing, is mediated, at least in part, by a p53-independent p21 upregulation, and is characterized by the arrest of MPM cells at the G2/M phase of the cell cycle. These results indicate that the two approaches act probably through different mechanisms and, thus, that DNMT1 silencing can be considered an effective alternative to Decitabine for cancer treatment.}, } @article {pmid19223589, year = {2009}, author = {Altomare, DA and Menges, CW and Pei, J and Zhang, L and Skele-Stump, KL and Carbone, M and Kane, AB and Testa, JR}, title = {Activated TNF-alpha/NF-kappaB signaling via down-regulation of Fas-associated factor 1 in asbestos-induced mesotheliomas from Arf knockout mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {106}, number = {9}, pages = {3420-3425}, pmid = {19223589}, issn = {1091-6490}, support = {R01 ES003721/ES/NIEHS NIH HHS/United States ; ES-03721/ES/NIEHS NIH HHS/United States ; CA-009035/CA/NCI NIH HHS/United States ; P30 CA006927/CA/NCI NIH HHS/United States ; CA-114047/CA/NCI NIH HHS/United States ; P01 CA114047/CA/NCI NIH HHS/United States ; CA-06927/CA/NCI NIH HHS/United States ; T32 CA009035/CA/NCI NIH HHS/United States ; }, mesh = {Adaptor Proteins, Signal Transducing ; Animals ; Apoptosis Regulatory Proteins ; Carrier Proteins/genetics/*metabolism ; Cyclin-Dependent Kinase Inhibitor p16/deficiency/genetics/*metabolism ; *Down-Regulation ; Intracellular Signaling Peptides and Proteins ; Mesothelioma/genetics/*metabolism/pathology ; Mice ; Mice, Knockout ; NF-kappa B/*metabolism ; *Signal Transduction ; Tumor Cells, Cultured ; Tumor Necrosis Factor-alpha/*metabolism ; }, abstract = {The human CDKN2A locus encodes 2 distinct proteins, p16(INK4A) and p14(ARF) [mouse p19(Arf)], designated INK4A (inhibitor of cyclin dependent kinase 4) and ARF (alternative reading frame) here, that are translated from alternatively spliced mRNAs. Human ARF is implicated as a tumor suppressor gene, mainly in association with the simultaneous deletion of INK4A. However, questions remain as to whether loss of ARF alone is sufficient to drive tumorigenesis. Here, we report that mice deficient for Arf are susceptible to accelerated asbestos-induced malignant mesothelioma (MM). MMs arising in Arf (+/-) mice consistently exhibit biallelic inactivation of Arf, but, unexpectedly, do not acquire additional recurrent genetic alterations that we previously identified in asbestos-induced MMs arising in Nf2 (+/-) mice. Array CGH analysis was used to detect a recurrent deletion at chromosome 4C6 in MMs from Arf (+/-) mice. A candidate gene in this region, Faf1 (FAS-associated factor 1), was further explored, because it encodes a protein implicated in tumor cell survival and in the pathogenesis of some human tumor types. We confirmed hemizygous loss of Faf1 and down-regulation of Faf1 protein in a series of MMs from Arf (+/-) mice, and we then showed that Faf1 regulates TNF-alpha-mediated NF-kappaB signaling, a pathway previously implicated in asbestos-induced oncogenesis of human mesothelial cells. Collectively, these data indicate that Arf inactivation has a significant role in driving MM pathogenesis, and implicate Faf1 as a key component in the TNF-alpha/NF-kappaB signaling node that has now been independently implicated in asbestos-induced oncogenesis.}, } @article {pmid19221957, year = {2008}, author = {Goldyn, SR and Condos, R and Rom, WN}, title = {The burden of exposure-related diffuse lung disease.}, journal = {Seminars in respiratory and critical care medicine}, volume = {29}, number = {6}, pages = {591-602}, pmid = {19221957}, issn = {1098-9048}, support = {T32 ES007267/ES/NIEHS NIH HHS/United States ; T32 ES007267-18/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Cost of Illness ; Government Regulation ; Humans ; Lung Diseases/chemically induced/*economics/epidemiology ; Occupational Diseases/chemically induced/*economics/epidemiology ; Occupational Exposure/adverse effects/*economics ; Prevalence ; United States/epidemiology ; }, abstract = {Estimating the burden of exposure-related diffuse lung disease in terms of health effects and economic burden remains challenging. Labor statistics are inadequate to define the scope of the problem, and few studies have analyzed the prevalence of exposure-related illnesses and the subsequent health care cost. Well-defined exposures, such as those associated with coal mines, asbestos mines, and stonecutting, have led to more accurate assessment of prevalence and cost. As governmental regulation of workplace exposure has increased, the prevalence of diseases such as silicosis and coal workers' pneumoconiosis has diminished. However, the health and economic effects of diseases with long latency periods, such as asbestosis and mesothelioma, continue to increase in the short term. Newer exposures, such as those related to air pollution, nylon flock, and the World Trade Center collapse, have added to these costs. As a result, estimates of cost for occupational diseases, including respiratory illnesses, exceed $26 billion annually, and the true economic burden is likely much higher.}, } @article {pmid19208334, year = {2009}, author = {Brauer, C and Baandrup, U and Jacobsen, P and Krasnik, M and Olsen, JH and Pedersen, JH and Rasmussen, TR and Schlünssen, V and Sherson, D and Svolgaard, B and Sørensen, JB and Omland, O}, title = {[Screening for asbestos-related conditions].}, journal = {Ugeskrift for laeger}, volume = {171}, number = {6}, pages = {433-436}, pmid = {19208334}, issn = {1603-6824}, mesh = {Asbestos/*adverse effects ; Denmark/epidemiology ; Humans ; Incidence ; Lung Diseases/epidemiology/etiology ; Lung Neoplasms/epidemiology/*etiology ; Mass Screening ; Mesothelioma/epidemiology/*etiology ; Occupational Diseases/epidemiology/*etiology ; Pleural Diseases/epidemiology/etiology ; }, abstract = {Screening programs for early detection of asbestos-related cancer have been considered. Conventional X-ray, computed tomography of the thorax, and the biomarkers osteopontin and mesothelin have been critically reviewed in the literature, together with survival data from screening programs in asbestos-exposed populations. Data do not currently support implementation of screening programs for asbestos-exposed persons in Denmark. Since mesothelioma is most often an occupational disease, these patients should be admitted to an occupational clinic for aetiological evaluation.}, } @article {pmid19203317, year = {2009}, author = {O'Lone, EL and Park, EK and Sandrini, A and Fogarty, GB and Yates, DH}, title = {Early detection of malignant pleural mesothelioma through measurement of soluble mesothelin-related protein and positron emission tomography.}, journal = {The Medical journal of Australia}, volume = {190}, number = {3}, pages = {158-159}, doi = {10.5694/j.1326-5377.2009.tb02321.x}, pmid = {19203317}, issn = {0025-729X}, mesh = {Asbestos/toxicity ; Early Detection of Cancer ; GPI-Linked Proteins ; Humans ; Hydropneumothorax/*diagnosis/diagnostic imaging/etiology/metabolism ; Male ; Membrane Glycoproteins/*metabolism ; Mesothelin ; Mesothelioma/*diagnosis/diagnostic imaging/etiology/metabolism ; Middle Aged ; *Positron-Emission Tomography ; Time Factors ; }, abstract = {A 51-year-old man with no known history of asbestos exposure presented with hydropneumothorax. Soluble mesothelin-related protein testing and combined positron emission tomography and computed tomography were used to diagnose malignant pleural mesothelioma. One year after radical surgery and radiotherapy, there was no clinical recurrence.}, } @article {pmid19192718, year = {2008}, author = {Tada, Y and Takiguchi, Y and Hiroshima, K and Shimada, H and Ueyama, T and Nakamura, M and Tatsumi, K and Kuriyama, T and Tagawa, M}, title = {Gene therapy for malignant pleural mesothelioma: present and future.}, journal = {Oncology research}, volume = {17}, number = {6}, pages = {239-246}, doi = {10.3727/096504008786991602}, pmid = {19192718}, issn = {0965-0407}, mesh = {Clinical Trials as Topic ; Cytokines/genetics/metabolism ; Genes, Tumor Suppressor ; Genetic Therapy/*methods/trends ; Humans ; Immunotherapy/methods ; Mesothelioma/genetics/metabolism/*therapy ; Pleural Neoplasms/genetics/metabolism/*therapy ; Thymidine Kinase/genetics/metabolism ; }, abstract = {Malignant pleural mesothelioma is relatively rare in frequency but one of the intractable diseases linked with asbestos exposure. Clinical outcomes with the present treatment modalities are unsatisfactory and no effective prevention method has been reported. Growing numbers of the patients in the Western countries with a long latent period need development of a novel therapeutic strategy. Gene therapy is a candidate for mesothelioma treatment because of its easy accessibility of a vector-mediated gene medicine into the intrapleural cavity. Several preclinical studies demonstrated that the gene medicine produced antitumor effects, suggesting the feasibility in clinical settings. In this article, we review the current status of gene therapy and clinical trials targeting mesothelioma and address possible directions to improve the efficacy.}, } @article {pmid19190155, year = {2009}, author = {Rodríguez Portal, JA and Rodríguez Becerra, E and Rodríguez Rodríguez, D and Alfageme Michavila, I and Quero Martínez, A and Diego Roza, C and León Jiménez, A and Isidro Montes, I and Cebollero Rivas, P}, title = {Serum levels of soluble mesothelin-related peptides in malignant and nonmalignant asbestos-related pleural disease: relation with past asbestos exposure.}, journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology}, volume = {18}, number = {2}, pages = {646-650}, doi = {10.1158/1055-9965.EPI-08-0422}, pmid = {19190155}, issn = {1055-9965}, mesh = {Adult ; Area Under Curve ; Asbestosis/*blood ; Biomarkers, Tumor/*blood ; Cross-Sectional Studies ; Enzyme-Linked Immunosorbent Assay ; Female ; GPI-Linked Proteins ; Humans ; Male ; Membrane Glycoproteins/*blood ; Mesothelin ; Mesothelioma/*blood/chemically induced ; Middle Aged ; Pleural Neoplasms/*blood/chemically induced ; Prospective Studies ; ROC Curve ; Statistics, Nonparametric ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) results from malignant transformation of mesothelial cells. Past asbestos exposure represents a major risk factor for MPM and other benign pleural disease. Soluble mesothelin-related peptides (SMRP) have been regarded as a promising serum biomarker for MPM. The aim of this study was to investigate serum levels of SMRP in malignant and nonmalignant asbestos-related pleural disease.

PATIENTS: Four groups of patients were investigated: group 1 composed of 48 healthy subjects, group 2 composed of 177 patients with previous asbestos exposure and no pleural disease, group 3 composed of 36 patients with MPM, and group 4 composed of 101 patients with previous asbestos exposure and benign pleural disease. Serum SMRP levels were determined by ELISA.

RESULTS: Serum SMRP levels were significantly higher among group 3 than the other three groups. There were no differences in SMRP concentrations between groups 2 and 4. Subjects exposed to asbestos had higher SMRP concentrations than normal control subjects regardless of the presence of pleural disease. The area under the receiver operating characteristic curve for SMRP values was 0.75 (95% confidence interval, 0.68-0.83). The SMRP level at 0.55 nmol/L/L was determined as the most optimal cutoff value with resulting sensitivity and specificity of 72% and 72% for the diagnosis of MPM.

CONCLUSIONS: These data attest to good diagnostic sensitivity and specificity of SMRP for the diagnosis of malignant mesothelioma. We have also shown that serum SMRP levels might serve as a marker of asbestos exposure.}, } @article {pmid19182436, year = {2009}, author = {Sakamoto, Y and Nakae, D and Fukumori, N and Tayama, K and Maekawa, A and Imai, K and Hirose, A and Nishimura, T and Ohashi, N and Ogata, A}, title = {Induction of mesothelioma by a single intrascrotal administration of multi-wall carbon nanotube in intact male Fischer 344 rats.}, journal = {The Journal of toxicological sciences}, volume = {34}, number = {1}, pages = {65-76}, doi = {10.2131/jts.34.65}, pmid = {19182436}, issn = {1880-3989}, mesh = {Anemia/pathology ; Animals ; Asbestos, Crocidolite/chemistry/toxicity ; Ascites/diagnosis/pathology ; Autopsy/methods ; Carboxymethylcellulose Sodium/chemistry ; Carcinogens/chemistry/*toxicity ; Dose-Response Relationship, Drug ; Epithelium/pathology ; Granuloma/chemically induced/pathology ; *Injections ; Liver/pathology ; Male ; Mesothelioma/*chemically induced/pathology ; Nanotubes, Carbon/chemistry/*toxicity ; Particle Size ; Peritoneum/pathology ; Pharmaceutical Vehicles/administration & dosage/chemistry ; Rats ; Rats, Inbred F344 ; *Scrotum ; Suspensions/chemistry ; Time Factors ; Tissue Adhesions ; }, abstract = {The present study assessed a carcinogenic hazard of multi-wall carbon nanotube (MWCNT) in intact (not genetically modified) rodents. MWCNT (1 mg/kg body weight, 7 animals), crocidolite (2 mg/kg body weight, 10 animals) or vehicle (2% carboxymethyl cellulose, 5 animals) was administered to male Fischer 344 rats (12 weeks old) by a single intrascrotal injection. Rats were autopsied immediately after death, when becoming moribund or at the end of the maximal observation period scheduled to be 52 weeks. After 37-40 weeks, however, 6 MWCNT-treated animals died or became moribund due to intraperitoneally disseminated mesothelioma (6/7, 85.7%) with bloody ascites. Peritoneal mesothelium was generally hypertrophic, and numerous nodular or papillary lesions of mesothelioma and mesothelial hyperplasia were developed. While mesothelioid cells were predominant in relatively early stage tumors, advanced stage mesotheliomas were constituted by 2 portions occupied by mesothelioid cells on the surface and spindle-shaped sarcomatous cells in the depth. In the latter, the histological transition was apparently observed between these 2 portions. Mesotheliomas were invasive to adjacent organs and tissues, and frequently metastasized into the pleura. Only 1 rat survived for 52 weeks in the MWCNT-treated group, and similar findings except mesothelioma were observed. All 10 crocidolite-treated and 5 vehicle-treated rats survived for 52 weeks without any particular changes except deposition of asbestos in the former case. It is thus indicated that MWCNT possesses carcinogenicity causing mesothelioma at a high rate in intact male rats under the present experimental conditions. The present data identifies a carcinogenic hazard of MWCNT and will serve as one of the indispensable evidences to be used for the risk assessment crucial for not only protection and improvement of human health and welfare, but also safe and acceptable development and prevalence of this and similar upcoming materials.}, } @article {pmid19176370, year = {2009}, author = {Catalano, A and Lazzarini, R and Di Nuzzo, S and Orciari, S and Procopio, A}, title = {The plexin-A1 receptor activates vascular endothelial growth factor-receptor 2 and nuclear factor-kappaB to mediate survival and anchorage-independent growth of malignant mesothelioma cells.}, journal = {Cancer research}, volume = {69}, number = {4}, pages = {1485-1493}, doi = {10.1158/0008-5472.CAN-08-3659}, pmid = {19176370}, issn = {1538-7445}, mesh = {Apoptosis ; Cell Adhesion ; Cell Division ; Cell Survival ; Colony-Forming Units Assay ; Genes, Reporter ; Humans ; Immunoblotting ; Mesothelioma/genetics/*pathology ; NF-kappa B/*genetics/physiology ; Nerve Tissue Proteins/*genetics ; Phenotype ; Plasmids ; Pleural Neoplasms/genetics/*pathology ; RNA, Neoplasm/genetics ; Receptors, Cell Surface/*genetics ; Signal Transduction ; Transfection ; Vascular Endothelial Growth Factor Receptor-1/physiology ; Vascular Endothelial Growth Factor Receptor-2/*genetics ; }, abstract = {The semaphorins and their receptors, the neuropilins and the plexins, are constituents of a complex regulatory system that controls axonal guidance. Moreover, many types of tumor cells express various members of semaphorins and receptors, but the biological activities within tumor mass and the signal transduction mechanism(s) they use are largely unknown. Here, we show that in asbestos-related malignant pleural mesothelioma (MPM), Semaphorin-6D (Sema6D) and its receptor plexin-A1 are frequently expressed and trigger a prosurvival program that promotes anchorage-independent growth of MPM cells. Interestingly, the same response is also controlled by the tyrosine kinase receptors of vascular endothelial growth factor (VEGF) through a nuclear factor-kappaB (NF-kappaB)-dependent pathway. We found that in MPM cells, plexin-A1 and VEGF-receptor 2 (VEGF-R2) are associated in a complex. Moreover, the presence of Sema6D promotes the tyrosine phosphorylation of VEGF-R2 in a plexin-A1-dependent manner. This is necessary for basal and Sema6D-induced NF-kappaB transcriptional activity, and NF-kappaB mediates tumor cell survival. Expression of Sema6D and plexin-A1 is induced by asbestos fibers and overexpression of plexin-A1 in nonmalignant mesothelial cells inhibits cell death after asbestos exposure. This work identifies a new biological function of semaphorins in cancer cells and suggests the involvement of an undescribed survival pathway during MPM tumorigenesis.}, } @article {pmid19174489, year = {2009}, author = {Park, EK and Thomas, PS and Johnson, AR and Yates, DH}, title = {Osteopontin levels in an asbestos-exposed population.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {15}, number = {4}, pages = {1362-1366}, doi = {10.1158/1078-0432.CCR-08-0360}, pmid = {19174489}, issn = {1078-0432}, mesh = {Aged ; Asbestos/*adverse effects ; Cohort Studies ; Cross-Sectional Studies ; Humans ; Male ; Middle Aged ; *Occupational Exposure ; Osteopontin/*blood ; Prospective Studies ; }, abstract = {PURPOSE: Serum osteopontin levels in patients with malignant mesothelioma have been reported to be higher than in healthy subjects. This study assessed serum osteopontin levels in an asbestos-exposed population to test whether nonmalignant asbestos-related disorders could influence osteopontin levels.

EXPERIMENTAL DESIGN: This cross-sectional study evaluated serum osteopontin levels in 525 male subjects. Subjects were classified into six different diagnostic groups, including asbestosis (n=23), silicosis (n=20), diffuse pleural thickening (n=110), asbestosis and diffuse pleural thickening (n=13), pleural plaques (n=142), and healthy subjects with a history of asbestos exposure (n=217).

RESULTS: Mean serum osteopontin levels differed among the six groups (P<0.0001). Mean osteopontin values of the healthy individuals exposed to asbestos were significantly different from that of subjects with asbestosis (P<0.001) and diffuse pleural thickening (P<0.001). There was a significant difference in mean serum levels of osteopontin in healthy individuals exposed to asbestos (n=217) compared with the group mean of all subjects with asbestos-related disorders (n=288; P<0.0001).

CONCLUSIONS: Our results suggest that osteopontin levels are elevated in subjects with asbestos-related disorders without malignant mesothelioma. These data indicate that osteopontin, although reported to be useful for detecting malignant mesothelioma in asbestos-exposed individuals, may be influenced by nonmalignant processes.}, } @article {pmid19166594, year = {2009}, author = {Okello, C and Treasure, T and Nicholson, AG and Peto, J and Møller, H}, title = {Certified causes of death in patients with mesothelioma in South East England.}, journal = {BMC cancer}, volume = {9}, number = {}, pages = {28}, pmid = {19166594}, issn = {1471-2407}, mesh = {Aged ; Cause of Death ; *Death Certificates ; England/epidemiology ; Female ; Humans ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; Middle Aged ; }, abstract = {BACKGROUND: Mesothelioma is a highly fatal cancer that is caused by exposure to asbestos fibres. In many populations, the occurrence of mesothelioma is monitored with the use of mortality data from death certification. We examine certified causes of death of patients who have been diagnosed with mesothelioma, and assess the validity of death certification data as a proxy for mesothelioma incidence.

METHODS: We extracted mesothelioma registrations in the South East of England area between 2000 and 2004 from the Thames Cancer Registry database. We retained for analysis 2200 patients who had died at the time of analysis, after having excluded seven dead cases where the causes of death were not known to the cancer registry. The 2200 deaths were classified hierarchically to identify (1) mesothelioma deaths, (2) deaths certified as lung cancer deaths or (3) deaths from unspecified cancer, and (4) deaths from other causes.

RESULTS: 87% of the patients had mesothelioma mentioned on the death certificate. 6% had no mention of mesothelioma but included lung cancer as a cause of death. Another 6% had no mention of mesothelioma or lung cancer, but included an unspecified cancer as a cause of death. Lastly, 2% had other causes of death specified on the death certificate.

CONCLUSION: This analysis suggests that official mortality data may underestimate the true occurrence of mesothelioma by around 10%.}, } @article {pmid19158938, year = {2009}, author = {Kliment, CR and Clemens, K and Oury, TD}, title = {North american erionite-associated mesothelioma with pleural plaques and pulmonary fibrosis: a case report.}, journal = {International journal of clinical and experimental pathology}, volume = {2}, number = {4}, pages = {407-410}, pmid = {19158938}, issn = {1936-2625}, abstract = {Erionite, a fibrous zeolite mineral, has been categorized as a class I carcinogenic agent for its causative role in mesothelioma. In select villages in Turkey, erionite is the cause of more than 50% of mesotheliomas. In contrast, in the United States mesotheliomas are frequently associated with asbestos exposure. We describe the first reported case of a patient with erionite-associated pleural mesothelioma with classic pathologic changes typical of asbestos-related pulmonary and pleural pathology. This case report indicates that in addition to Turkey, erionite-associated disease can occur in North America and that subjects with erionite exposure are not only at risk of developing mesothelioma, but may develop interstitial fibrosis and additional pulmonary pathology impacting lung function and patient survival.}, } @article {pmid19152347, year = {2009}, author = {Maurel, M and Stoufflet, A and Thorel, L and Berna, V and Gislard, A and Letourneux, M and Pairon, JC and , and Paris, C}, title = {Factors associated with cancer distress in the Asbestos Post-Exposure Survey (APEXS).}, journal = {American journal of industrial medicine}, volume = {52}, number = {4}, pages = {288-296}, doi = {10.1002/ajim.20672}, pmid = {19152347}, issn = {1097-0274}, mesh = {Female ; France ; Humans ; Logistic Models ; Lung Neoplasms/diagnostic imaging/*psychology ; Male ; Mesothelioma/diagnostic imaging/*psychology ; Middle Aged ; Risk Factors ; Surveys and Questionnaires ; Tomography, X-Ray Computed/*psychology ; }, abstract = {OBJECTIVES: CT-scan screening programs for lung cancer detection have been proposed in high-risk subjects, and more recently in former asbestos-exposed subjects. However, to date no data are available on psychological impact of such programs. The aim of this study is to examine the risk factors of psychological distress at baseline of a CT-scan screening program among asbestos-exposed subjects.

METHODS: The Asbestos Post-Exposure Survey (APEXS) was carried out in France between October 2003 and December 2005 in order to screen asbestos-related diseases by CT-scan. Volunteers underwent self-administered questionnaires including an asbestos exposure assessment and, for a large sub-sample, a validated psychological distress scale. Non-exposed subjects were used as reference group.

RESULTS: At baseline, a significant higher level of distress was observed in exposed subjects (n = 3,122) relative to the reference group (n = 486) after adjustment on age, sex, and tobacco status. This distress is associated independently with the self-perception of (i) intensity of asbestos exposure and (ii) the risk of current or future disease related to the asbestos exposure. The perception of the cancer risk related to asbestos seems to play a fundamental role in this psychological distress.

CONCLUSION: In this study, asbestos-exposed subjects experienced a higher significant cancer distress than previously described in literature. These findings may be of potential public health importance. First, the impact of such occupational exposures on quality of life of patients who suffer from cancer related to these exposures has to be appraised. Secondly, the assessment of psychological impact of CT-scan screening programs among asbestos-exposed subjects is also required.}, } @article {pmid19143009, year = {2009}, author = {Yano, E and Wang, ZM and Wang, XR and Wang, MZ and Takata, A and Kohyama, N and Suzuki, Y}, title = {Mesothelioma in a worker who spun chrysotile asbestos at home during childhood.}, journal = {American journal of industrial medicine}, volume = {52}, number = {4}, pages = {282-287}, doi = {10.1002/ajim.20675}, pmid = {19143009}, issn = {1097-0274}, mesh = {Adult ; Asbestos, Serpentine/*toxicity ; China ; Environmental Exposure/*adverse effects ; Humans ; Lung Neoplasms/*diagnosis ; Male ; Mesothelioma/*diagnosis ; Occupational Diseases/*diagnosis ; Occupational Exposure/*adverse effects ; Risk Factors ; }, abstract = {BACKGROUND: Malignant mesothelioma has a long latency period and more commonly found in those exposed to amphibole than chrysotile asbestos.

METHOD: A 35 years old asbestos worker in an asbestos textile plant in Chongqing, China, developed mesothelioma after only 4 years of employment. He was born and bred in a company residence of an asbestos plant and manually spun asbestos thread during school age. In the plant, not amphibole but only chrysotile has been used.

RESULTS: Diagnosis of malignant mesothelioma was confirmed by comprehensive approaches including gross appearance, histology, histochemistry, and immunocytochemistry. In the lung and tumor tissues, huge number of tremolite with exceptional chrysotile was observed despite the reverse proportion in the work environment.

DISCUSSION: Residential exposure and home spinning of asbestos seemed contributed to the early development of mesothelioma in this subject. Although only chrysotile was used and contamination of tremolite was low in the work environment, chrysotile seemed to be cleared leaving tremolite remain in the tissue.

CONCLUSION: Chrysotile with little contamination of tremolite can lead to early development of malignant mesothelioma when heavily exposed from childhood at a company residence with household exposure. There can be several mechanisms for tremolite to remain in the lung tissue, far exceeding chrysotile in number.}, } @article {pmid19129058, year = {2008}, author = {Chen, HC and Tsai, KB and Wang, CS and Hsieh, TJ and Hsu, JS}, title = {Duodenal metastasis of malignant pleural mesothelioma.}, journal = {Journal of the Formosan Medical Association = Taiwan yi zhi}, volume = {107}, number = {12}, pages = {961-964}, doi = {10.1016/S0929-6646(09)60021-8}, pmid = {19129058}, issn = {0929-6646}, mesh = {Aged ; Biopsy ; Diagnosis, Differential ; Duodenal Neoplasms/diagnosis/*secondary ; Endoscopy, Gastrointestinal ; Fatal Outcome ; Humans ; Male ; Mesothelioma/diagnosis/*secondary ; Pleural Neoplasms/diagnostic imaging/*pathology ; Radiography, Thoracic ; Tomography, X-Ray Computed ; }, abstract = {Metastatic malignant mesothelioma of the pleura is uncommon at the time of initial diagnosis. The gastrointestinal lumen is rarely found at autopsy in patients with widespread disease. Here, we describe an extremely rare case of isolated duodenal metastasis of sarcomatoid mesothelioma of the pleura in a 73-year-old man, without memory of any direct exposure to asbestos. The possibility of gastrointestinal tract metastasis should be considered in the presence of anemia or positive occult blood test in patients with malignant pleural mesothelioma.}, } @article {pmid19125709, year = {2008}, author = {Cukić, V and Ustamujić, A and Lovre, V and Zutić, H and Genjac, S and Masić-Zecević, M}, title = {Malignant pleural mesothelioma treated in Clinic for Pulmonary Diseases and Tuberculosis "Podhrastovi" in ten-year period (from 1998 to 2007).}, journal = {Bosnian journal of basic medical sciences}, volume = {8}, number = {4}, pages = {361-366}, pmid = {19125709}, issn = {1512-8601}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Bosnia and Herzegovina/epidemiology ; Female ; Humans ; Male ; Mesothelioma/diagnosis/*epidemiology/etiology/therapy ; Middle Aged ; Pleural Neoplasms/diagnosis/*epidemiology/etiology/therapy ; Retrospective Studies ; }, abstract = {Malignant pleural mesothelioma (MPM) is the most common primary malign tumour of pleura. The aim of this study was to evaluate cases of MPM diagnosed and treated in Clinic for Pulmonary Diseases and Tuberculosis "Podhrastovi" during ten-year period (1998-2007). Study is retrospective. The patients were analysed according to age, sex, histopathologic type of the tumour, cantonal distribution in Federation of Bosnia and Herzegovina and regimen of treatment. MPM presented 0,72% (0-1,56% per year) of all hospitalised malignant patients, and the greatest number of registered cases was in the year of 2007. The series included 16 male (57,14%) and 12 female (42,86%). Cases over 64 years old were the most frequent (14-50%) than 45-54 years (7- not 25%). Histopathology types of hospitalised cases of MPM: epitheloid form (8- 28,57%); sarcomatoid form (2- 7,14 %); other forms (18-64,29%). The most patients came from Canton Sarajevo (12-42,86%); ZE-DO canton (8-28,57%) and the UNA-SANA canton (5-17,86%). The therapy applied: chemotherapy (11-39,29%); radiotherapy (3-10,71%); chemotherapy + radiotherapy (4-14,29%); symptomatic therapy (10-35,71 %).}, } @article {pmid19124491, year = {2009}, author = {Reid, A and Segal, A and Heyworth, JS and de Klerk, NH and Musk, AW}, title = {Gynecologic and breast cancers in women after exposure to blue asbestos at Wittenoom.}, journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology}, volume = {18}, number = {1}, pages = {140-147}, doi = {10.1158/1055-9965.EPI-08-0746}, pmid = {19124491}, issn = {1055-9965}, mesh = {Adenocarcinoma/chemically induced/epidemiology ; Adolescent ; Adult ; Aged, 80 and over ; Asbestos, Crocidolite/*toxicity ; Breast Neoplasms/*chemically induced/epidemiology ; Case-Control Studies ; Environmental Exposure/*adverse effects ; Female ; Humans ; Incidence ; Logistic Models ; Occupational Exposure/*adverse effects ; Ovarian Neoplasms/*chemically induced/epidemiology ; Uterine Cervical Neoplasms/*chemically induced/epidemiology ; Western Australia/epidemiology ; }, abstract = {INTRODUCTION: Animal studies have suggested an association between asbestos and ovarian cancer, and asbestos fibers have been detected in human ovaries. Sexual intercourse may introduce asbestos fibers into the vagina and to the cervix and ovaries. Occupational cohorts have reported excess mortality from reproductive cancers, but exposure-response relationships are inconsistent. We examine the incidence and exposure-response relationships of these cancers among 2,968 women and girls exposed to blue asbestos at Wittenoom, Western Australia.

METHODS: 2,552 women were residents of the town and 416 worked for the asbestos company (Australian Blue Asbestos). Standardized incidence ratios compared the Wittenoom women with the Western Australian population. A nested case-control design and conditional logistic regression examined exposure-response relationships.

RESULTS: Ovarian (standardized incidence ratio, 1.27), cervical (standardized incidence ratio, 1.44), and uterine cancer (standardized incidence ratio, 1.23) increased but not statistically significantly among the Wittenoom women compared with the Western Australian population. Among the Australian Blue Asbestos workers, cervical cancer was twice that of the Western Australian population (standardized incidence ratio, 2.38), but ovarian cancer was less (standardized incidence ratio, 0.65). Women who first arrived at Wittenoom aged >or=40 years had an odds ratio of 13.9 (95% confidence interval, 2.2-90.2) for cervical cancer compared with those aged <15 years at first arrival. Women who lived with or washed the clothes of an Australian Blue Asbestos worker did not have an increased risk for any of the gynecologic or breast cancers.

DISCUSSION: There is no consistent evidence of an increased risk for gynecologic and breast cancers among the women from Wittenoom. Ovarian cancers and peritoneal mesotheliomas were not misclassified in this cohort.}, } @article {pmid19118007, year = {2009}, author = {Christensen, BC and Houseman, EA and Godleski, JJ and Marsit, CJ and Longacker, JL and Roelofs, CR and Karagas, MR and Wrensch, MR and Yeh, RF and Nelson, HH and Wiemels, JL and Zheng, S and Wiencke, JK and Bueno, R and Sugarbaker, DJ and Kelsey, KT}, title = {Epigenetic profiles distinguish pleural mesothelioma from normal pleura and predict lung asbestos burden and clinical outcome.}, journal = {Cancer research}, volume = {69}, number = {1}, pages = {227-234}, pmid = {19118007}, issn = {1538-7445}, support = {T32 ES 007155/ES/NIEHS NIH HHS/United States ; R01 CA 126939/CA/NCI NIH HHS/United States ; P42 ES 05947/ES/NIEHS NIH HHS/United States ; T32 ES007155-22/ES/NIEHS NIH HHS/United States ; P42 ES005947/ES/NIEHS NIH HHS/United States ; R01 CA126939-01A1/CA/NCI NIH HHS/United States ; R01 CA126939/CA/NCI NIH HHS/United States ; T32 ES007155/ES/NIEHS NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*analysis ; CpG Islands ; DNA Methylation ; Epigenesis, Genetic ; Female ; Humans ; Lung/chemistry ; Male ; Mesothelioma/chemistry/*genetics/surgery ; Middle Aged ; Pleura/chemistry ; Pleural Neoplasms/chemistry/*genetics/surgery ; }, abstract = {Mechanisms of action of nonmutagenic carcinogens such as asbestos remain poorly characterized. As pleural mesothelioma is known to have limited numbers of genetic mutations, we aimed to characterize the relationships among gene-locus-specific methylation alterations, disease status, asbestos burden, and survival in this rapidly fatal asbestos-associated tumor. Methylation of 1505 CpG loci associated with 803 cancer-related genes were studied in 158 pleural mesotheliomas and 18 normal pleura. After false-discovery rate correction, 969 CpG loci were independently associated with disease status (Q < 0.05). Classifying samples based on CpG methylation profile with a mixture model approach, methylation classes discriminated tumor from normal pleura (permutation P < 0.0001). In a random forests classification, the overall misclassification error rate was 3.4%, with <1% (n = 1) of tumors misclassified as normal (P < 0.0001). Among tumors, methylation class membership was significantly associated with lung tissue asbestos body burden (P < 0.03), and significantly predicted survival (likelihood ratio P < 0.01). Consistent with prior work, asbestos burden was associated with an increased risk of death (hazard ratio, 1.4; 95% confidence interval, 1.1-1.8). Our results have shown that methylation profiles powerfully differentiate diseased pleura from nontumor pleura and that asbestos burden and methylation profiles are independent predictors of mesothelioma patient survival. We have added to the growing body of evidence that cellular epigenetic dysregulation is a critical mode of action for asbestos in the induction of pleural mesothelioma. Importantly, these findings hold great promise for using epigenetic profiling in the diagnosis and prognosis of human cancers.}, } @article {pmid19105609, year = {2009}, author = {Archimandriti, DT and Dalavanga, YA and Cianti, R and Bianchi, L and Manda-Stachouli, C and Armini, A and Koukkou, AI and Rottoli, P and Constantopoulos, SH and Bini, L}, title = {Proteome analysis of bronchoalveolar lavage in individuals from Metsovo, nonoccupationally exposed to asbestos.}, journal = {Journal of proteome research}, volume = {8}, number = {2}, pages = {860-869}, doi = {10.1021/pr800370n}, pmid = {19105609}, issn = {1535-3893}, mesh = {Asbestos/*adverse effects ; Bronchoalveolar Lavage Fluid/*chemistry ; Cluster Analysis ; Greece ; Humans ; *Mesothelioma/chemistry/etiology ; Molecular Sequence Data ; Pleural Diseases/*etiology ; Proteins/*analysis ; Proteome/*analysis ; }, abstract = {Inhabitants of Metsovo, NW Greece, have been exposed to an asbestos whitewash, resulting in malignant pleural mesothelioma (MPM) and pleural calcifications (PCs). Interestingly, those with PCs (PC(+)) are less prone to MPM. They also have lymphocytic alveolitis, and differences in bronchoalveolar lavage (BAL) proteins, compared with those without pleural calcifications (PC(-)). This may mean a different response to the fiber leading to different susceptibility to neoplasia. To further evaluate this, a proteomic analysis of BAL proteins was performed. Proteomic analysis (2D-electrophoresis/Mass Spectrometry) of BAL in Metsovites nonoccupationally exposed to asbestos revealed increased albumin fragments, alpha1-antitrypsin, S100-A9 and HSP27, suggesting ongoing inflammation. In those without pleural calcifications, increased expression of acid ceramidase, glutathione-S-transferase and presence of calcyphosin, all involved in cell cycle regulation and death as well as in the detoxification of mutagenic and toxic agents, lend further support to our thesis of possible "protection against neoplasia" in Metsovites with pleural calcifications.}, } @article {pmid19099560, year = {2008}, author = {Moore, AJ and Parker, RJ and Wiggins, J}, title = {Malignant mesothelioma.}, journal = {Orphanet journal of rare diseases}, volume = {3}, number = {}, pages = {34}, pmid = {19099560}, issn = {1750-1172}, mesh = {Humans ; Mesothelioma/*diagnosis/diagnostic imaging/etiology/*pathology ; Pleural Neoplasms/*diagnosis/diagnostic imaging/etiology/*pathology ; Tomography, X-Ray Computed ; }, abstract = {Malignant mesothelioma is a fatal asbestos-associated malignancy originating from the lining cells (mesothelium) of the pleural and peritoneal cavities, as well as the pericardium and the tunica vaginalis. The exact prevalence is unknown but it is estimated that mesotheliomas represent less than 1% of all cancers. Its incidence is increasing, with an expected peak in the next 10-20 years. Pleural malignant mesothelioma is the most common form of mesothelioma. Typical presenting features are those of chest pain and dyspnoea. Breathlessness due to a pleural effusion without chest pain is reported in about 30% of patients. A chest wall mass, weight loss, sweating, abdominal pain and ascites (due to peritoneal involvement) are less common presentations. Mesothelioma is directly attributable to occupational asbestos exposure with a history of exposure in over 90% of cases. There is also evidence that mesothelioma may result from both para-occupational exposure and non-occupational "environmental" exposure. Idiopathic or spontaneous mesothelioma can also occur in the absence of any exposure to asbestos, with a spontaneous rate in humans of around one per million. A combination of accurate exposure history, along with examination radiology and pathology are essential to make the diagnosis. Distinguishing malignant from benign pleural disease can be challenging. The most helpful CT findings suggesting malignant pleural disease are 1) a circumferential pleural rind, 2) nodular pleural thickening, 3) pleural thickening of > 1 cm and 4) mediastinal pleural involvement. Involvement of a multidisciplinary team is recommended to ensure prompt and appropriate management, using a framework of radiotherapy, chemotherapy, surgery and symptom palliation with end of life care. Compensation issues must also be considered. Life expectancy in malignant mesothelioma is poor, with a median survival of about one year following diagnosis.}, } @article {pmid19092485, year = {2008}, author = {Stayner, LT}, title = {Canada, chrysotile and cancer: Health Canada's Asbestos International Expert Panel report.}, journal = {Journal of occupational and environmental medicine}, volume = {50}, number = {12}, pages = {1327-1328}, doi = {10.1097/JOM.0b013e318190eff3}, pmid = {19092485}, issn = {1536-5948}, mesh = {Asbestos ; Asbestos, Serpentine/*adverse effects ; Asbestosis/etiology ; Canada ; *Consensus Development Conferences as Topic ; Humans ; Lung Neoplasms/chemically induced ; Mesothelioma/chemically induced ; Neoplasms/chemically induced ; *Politics ; Quebec ; }, } @article {pmid19088405, year = {2008}, author = {Park, EK and Hannaford-Turner, KM and Hyland, RA and Johnson, AR and Yates, DH}, title = {Asbestos-related occupational lung diseases in NSW, Australia and potential exposure of the general population.}, journal = {Industrial health}, volume = {46}, number = {6}, pages = {535-540}, doi = {10.2486/indhealth.46.535}, pmid = {19088405}, issn = {1880-8026}, mesh = {Asbestos/*adverse effects ; Humans ; *Lung Diseases/etiology ; Mesothelioma/etiology ; New South Wales ; *Occupational Exposure ; *Public Health ; Risk Assessment ; }, abstract = {Asbestos is a fibrous silicate which is recognized as causing a variety of lung disorders including malignant mesothelioma of the pleura, lung cancer and asbestosis. Asbestos use has been banned in most developed countries but exposure still occurs under strict regulation in occupational settings and also occasionally in domestic settings. Although the hazards of asbestos are well known in developed countries, awareness of its adverse health effects is less in other parts of the world, particularly when exposure occurs in non-occupational settings. Experience of asbestos use and its adverse heath effects in developed countries such as Australia have resulted in development of expertise in the diagnosis and treatment of asbestos-related diseases as well as in screening and this can be used to help developing countries facing the issue of asbestos exposure.}, } @article {pmid19079719, year = {2008}, author = {Nishikawa, K and Takahashi, K and Karjalainen, A and Wen, CP and Furuya, S and Hoshuyama, T and Todoroki, M and Kiyomoto, Y and Wilson, D and Higashi, T and Ohtaki, M and Pan, G and Wagner, G}, title = {Recent mortality from pleural mesothelioma, historical patterns of asbestos use, and adoption of bans: a global assessment.}, journal = {Environmental health perspectives}, volume = {116}, number = {12}, pages = {1675-1680}, pmid = {19079719}, issn = {0091-6765}, mesh = {Asbestos/*toxicity ; Carcinogens/*toxicity ; Global Health ; Humans ; Mesothelioma/chemically induced/*mortality ; Mortality/trends ; Pleural Neoplasms/chemically induced/*mortality ; }, abstract = {BACKGROUND: In response to the health risks posed by asbestos exposure, some countries have imposed strict regulations and adopted bans, whereas other countries have intervened less and continue to use varying quantities of asbestos.

OBJECTIVES: This study was designed to assess, on a global scale, national experiences of recent mortality from pleural mesothelioma, historical trends in asbestos use, adoption of bans, and their possible interrelationships.

METHODS: For 31 countries with available data, we analyzed recent pleural mesothelioma (International Classification of Diseases, 10th Revision) mortality rates (MRs) using age-adjusted period MRs (deaths/million/year) from 1996 to 2005. We calculated annual percent changes (APCs) in age-adjusted MRs to characterize trends during the period. We characterized historical patterns of asbestos use by per capita asbestos use (kilograms per capita/year) and the status of national bans.

RESULTS: Period MRs increased with statistical significance in five countries, with marginal significance in two countries, and were equivocal in 24 countries (five countries in Northern and Western Europe recorded negative APC values). Countries adopting asbestos bans reduced use rates about twice as fast as those not adopting bans. Turning points in use preceded bans. Change in asbestos use during 1970-1985 was a significant predictor of APC in mortality for pleural mesothelioma, with an adjusted R(2) value of 0.47 (p < 0.0001).

CONCLUSIONS: The observed disparities in global mesothelioma trends likely relate to country-to-country disparities in asbestos use trends.}, } @article {pmid19070904, year = {2009}, author = {Pancaldi, C and Balatti, V and Guaschino, R and Vaniglia, F and Corallini, A and Martini, F and Mutti, L and Tognon, M}, title = {Simian virus 40 sequences in blood specimens from healthy individuals of Casale Monferrato, an industrial town with a history of asbestos pollution.}, journal = {The Journal of infection}, volume = {58}, number = {1}, pages = {53-60}, doi = {10.1016/j.jinf.2008.10.014}, pmid = {19070904}, issn = {1532-2742}, mesh = {Adult ; Aged ; *Asbestos ; Blood/*virology ; DNA, Viral/genetics ; Humans ; Industry ; *Inhalation Exposure ; Italy/epidemiology ; Leukocytes/virology ; Middle Aged ; Polymerase Chain Reaction/methods ; Polyomavirus Infections/*epidemiology ; Simian virus 40/*isolation & purification ; Tumor Virus Infections/*epidemiology ; Urban Population ; }, abstract = {OBJECTIVE: Asbestos is considered the main agent in causing the onset of the malignant pleural mesothelioma (MM), a fatal cancer of increasing incidence worldwide. Other factors may contribute to the onset/progression of MM, such as genetic predisposition and infection by oncogenic viruses, like simian virus 40 (SV40). SV40 was administered to human populations mainly with SV40-contaminated anti-polio vaccines. SV40 footprints have been detected in specific human tumours, including MM, and in healthy blood donors. The aim of this study was to verify the presence of SV40 sequences in buffy coats of healthy blood donors, inhabitants of Casale Monferrato, where MM is 10 times more prevalent compared to other areas.

METHODS: DNA from 148 buffy coats of healthy blood donors were qualitatively and quantitatively PCR analyzed for SV40 sequences.

RESULTS: SV40 sequences were detected in 24 out of 148 (16%) samples. Quantitative real time PCR analyses carried out in SV40-positive samples indicated a viral copy number in the range of 10-10,000 per 100,000 cells.

CONCLUSIONS: SV40 sequences are present in blood samples of healthy donors from Casale Monferrato with a prevalence similar to that reported in previous investigations of healthy donors from asbestos-free areas. Altogether these data suggest that SV40 is circulating in the human population.}, } @article {pmid19059033, year = {2008}, author = {}, title = {Asbestos-related disease--a preventable burden.}, journal = {Lancet (London, England)}, volume = {372}, number = {9654}, pages = {1927}, doi = {10.1016/S0140-6736(08)61821-8}, pmid = {19059033}, issn = {1474-547X}, mesh = {Asbestos/*adverse effects/classification ; Humans ; Mesothelioma/*etiology/mortality/*prevention & control ; Occupational Exposure/*adverse effects/*economics/legislation & jurisprudence ; United Kingdom ; Workers' Compensation/economics/*legislation & jurisprudence ; }, } @article {pmid19052741, year = {2009}, author = {van der Most, RG and Currie, AJ and Mahendran, S and Prosser, A and Darabi, A and Robinson, BW and Nowak, AK and Lake, RA}, title = {Tumor eradication after cyclophosphamide depends on concurrent depletion of regulatory T cells: a role for cycling TNFR2-expressing effector-suppressor T cells in limiting effective chemotherapy.}, journal = {Cancer immunology, immunotherapy : CII}, volume = {58}, number = {8}, pages = {1219-1228}, pmid = {19052741}, issn = {1432-0851}, mesh = {Adoptive Transfer ; Animals ; Antigens, Differentiation, T-Lymphocyte/immunology/metabolism ; CD8-Positive T-Lymphocytes/*immunology/metabolism ; Cyclophosphamide/*therapeutic use ; Deoxycytidine/analogs & derivatives/therapeutic use ; Immunosuppressive Agents/*therapeutic use ; Inducible T-Cell Co-Stimulator Protein ; Kaplan-Meier Estimate ; Ki-67 Antigen/immunology/metabolism ; L-Selectin/immunology/metabolism ; *Lymphocyte Depletion ; Mesothelioma/*drug therapy/immunology ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Receptors, Tumor Necrosis Factor, Type II/*immunology/metabolism ; T-Lymphocytes, Regulatory/*drug effects/immunology ; Gemcitabine ; }, abstract = {Tumor cell death potentially engages with the immune system. However, the efficacy of anti-tumor chemotherapy may be limited by tumor-driven immunosuppression, e.g., through CD25+ regulatory T cells. We addressed this question in a mouse model of mesothelioma by depleting or reconstituting CD25+ regulatory T cells in combination with two different chemotherapeutic drugs. We found that the efficacy of cyclophosphamide to eradicate established tumors, which has been linked to regulatory T cell depletion, was negated by adoptive transfer of CD25+ regulatory T cells. Analysis of post-chemotherapy regulatory T cell populations revealed that cyclophosphamide depleted cycling (Ki-67(hi)) T cells, including foxp3+ regulatory CD4+ T cells. Ki-67(hi) CD4+ T cells expressed increased levels of two markers, TNFR2 and ICOS, that have been associated with a maximally suppressive phenotype according to recently published studies. This suggest that cyclophosphamide depletes a population of maximally suppressive regulatory T cells, which may explain its superior anti-tumor efficacy in our model. Our data suggest that regulatory T cell depletion could be used to improve the efficacy of anti-cancer chemotherapy regimens. Indeed, we observed that the drug gemcitabine, which does not deplete cycling regulatory T cells, eradicates established tumors in mice only when CD25+ CD4+ T cells are concurrently depleted. Cyclophosphamide could be used to achieve regulatory T cell depletion in combination with chemotherapy.}, } @article {pmid19043291, year = {2008}, author = {Tsuda, H and Tokunaga, H and Hirose, A and Kanno, J}, title = {[Hazard identification of nanomaterials].}, journal = {Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan}, volume = {128}, number = {12}, pages = {1727-1732}, doi = {10.1248/yakushi.128.1727}, pmid = {19043291}, issn = {0031-6903}, mesh = {Animals ; Asbestos ; Fullerenes/toxicity ; Humans ; Mesothelioma/chemically induced ; Mice ; Nanostructures/adverse effects/*toxicity ; Nanotubes, Carbon/toxicity ; Particle Size ; Pharmacokinetics ; Rats ; Risk ; Safety ; Titanium/toxicity ; *Toxicity Tests ; }, abstract = {It is considered that the materials with new properties may lead to novel biological effects or unknown adverse health effects. To gather proper hazard information, it is important to develop both experimental protocols and detection/measurement methods for nanomaterials in the body, in parallel. Since 2005, we are running research projects to develop methods to monitor health risk effects for the assessment of manufactured nanomaterials funded by the Ministry of Health, Labour and Welfare. For the experimental protocols, these projects focus on the development of 1) in vitro experimental systems, 2) in vivo experimental systems (mainly focusing on long-term health implication, especially carcinogenesis), and 3) proper inhalation system. Firstly, fullerene (C60), titanium dioxide and multi-walled carbon nanotube were chosen to be tested because of their high production volume. Safety issues for new materials such as nanoparticles is a new paradigm. The key is that the full scale exposure to the public has not been started yet. Therefore, there is a good chance that information from hazard identification studies can be directly fed back to the product development plan. Manufacturers can produce safer products without risking themselves waiting for the toxicology studies to be finished after their products are widely marketed.}, } @article {pmid19040568, year = {2008}, author = {Sherwood, AL and Mutsaers, SE and Peeva, VK and Robinson, C and DeSilva, CJ and Swanson, NR and Lake, RA}, title = {Spontaneously immortalized mouse mesothelial cells display characteristics of malignant transformation.}, journal = {Cell proliferation}, volume = {41}, number = {6}, pages = {894-908}, pmid = {19040568}, issn = {1365-2184}, mesh = {Animals ; Cell Line, Transformed ; Cell Shape/drug effects ; Cell Transformation, Neoplastic/drug effects/*pathology ; Cellular Senescence/drug effects ; DNA/analysis ; Down-Regulation/drug effects ; Epithelial Cells/drug effects/metabolism/*pathology ; Gene Deletion ; Gene Expression Profiling ; Genes, Tumor Suppressor ; Humans ; Intercellular Signaling Peptides and Proteins/pharmacology ; Mesothelioma/genetics ; Mice ; Mice, Inbred C57BL ; }, abstract = {OBJECTIVES: Mesotheliomas occur in occult serous cavities after chronic exposure of mesothelial cells to asbestos fibres. Molecular events that contribute to the development of this cancer are therefore not readily accessible for study. We have used in vitro culture systems to study and compare induced and spontaneous transformation events in primary mouse mesothelial cells.

MATERIALS AND METHODS: Mouse mesothelial cells were cultivated until small populations of proliferating cells emerged from senescing cultures. Spontaneously transformed cultures of cells were characterized and compared to malignantly transformed cells.

RESULTS: Human mesothelial cells had a finite lifespan of 10-15 population doublings when cultured in vitro; mouse mesothelial cells typically exhibit this same pattern. Here, we show that mouse mesothelial cells can be cultured for extended periods and that these cells can transform spontaneously. Lines of spontaneously transformed cells generated in this study are immortal and growth factor-independent. They display the salient characteristic features of transformation, including increased proliferation rate, lack of contact inhibition, aneuploidy and ability to grow in anchorage-independent conditions. A subset of these cell lines developed into tumours in syngeneic mice. Comparative gene expression analysis demonstrated that spontaneously transformed cell lines were more closely related to neoplastic cells than to primary cells.

CONCLUSION: These findings have implications for interpretation of in vitro transformation studies, demonstrating broad similarity between spontaneous and induced genetic changes.}, } @article {pmid19035624, year = {2008}, author = {Greillier, L and Baas, P and Welch, JJ and Hasan, B and Passioukov, A}, title = {Biomarkers for malignant pleural mesothelioma: current status.}, journal = {Molecular diagnosis & therapy}, volume = {12}, number = {6}, pages = {375-390}, pmid = {19035624}, issn = {1177-1062}, mesh = {Antigens, Neoplasm/metabolism ; Biomarkers/*metabolism ; Clinical Trials as Topic ; GPI-Linked Proteins ; Humans ; Keratins/metabolism ; Membrane Glycoproteins/metabolism ; Mesothelin ; *Mesothelioma/diagnosis/metabolism/pathology ; Prognosis ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive tumor with poor prognosis, whose main etiology is exposure to asbestos fibers. The incidence of MPM is anticipated to increase worldwide during the first half of this century. For various reasons, MPM is difficult to diagnose and is notoriously refractory to most treatments. However, recently two active chemotherapy regimens have been demonstrated to significantly increase survival in patients with MPM, and several therapeutic agents and strategies are currently under evaluation.Researchers have actively sought MPM biomarkers for more than 20 years. Biomarkers would be helpful in managing three clinical aspects of MPM: early diagnosis, prognosis, and treatment outcome prediction. The aims of the present review are to summarize the published and recently presented data on MPM biomarkers and to identify the prospects for future translational research projects.Among the 'classical' diagnostic biomarkers measured in biological fluids, such as cytokeratins and cell surface antigens, none discriminate patients with MPM from those with other malignancies and nonmalignant diseases. Osteopontin, soluble mesothelin, and megakaryocyte potentiating factor (MPF) appear to be the most promising of the recent biomarkers, but are still subject to some limitations. Osteopontin lacks specificity for mesothelioma, while both soluble mesothelin and MPF lack sensitivity for detecting non-epithelial subtypes. Panels consisting of a small set of biomarkers do not improve the diagnostic yield, and results from molecular profiling are too preliminary to be brought into daily clinical practice. While a large number of biomarkers have been assessed in biological fluids and tumor tissue for their prognostic value, none have had a widespread impact on clinical practice. In contrast, data concerning predictive biomarkers are very limited, even though they are most interesting from the perspective of clinicians.Additional prospective studies, in large and independent samples of patients, with rigorous statistical methodology and standardized laboratory techniques are now warranted to validate and define the precise value of diagnostic and prognostic MPM biomarkers. Future research efforts should focus on biomarkers predictive of the efficacy and toxicity of standard chemotherapy. Translational research should be systematically incorporated into the design of clinical trials assessing new targeted agents in MPM.}, } @article {pmid18971823, year = {2008}, author = {Pairon, JC and Andujar, P and Matrat, M and Ameille, J}, title = {[Etiology, epidemiology, biology. Occupational respiratory cancers].}, journal = {Revue des maladies respiratoires}, volume = {25}, number = {8 Pt 2}, pages = {3S18-31}, pmid = {18971823}, issn = {0761-8425}, mesh = {Humans ; Lung Neoplasms/*epidemiology/etiology ; Mesothelioma/*epidemiology/etiology ; Occupational Diseases/*epidemiology ; Pleural Neoplasms/*epidemiology/etiology ; Population Surveillance ; }, abstract = {Lung cancer and pleural mesothelioma are the most common occupational cancers. Recent epidemiological studies have estimated that the fraction attributable to occupational factors varies from 13 to 29% for lung cancer in men and is about 85% for pleural mesothelioma in men. Previous occupational exposure to asbestos is the most common occupational exposure in these cancers. Mesothelioma immediately leads the clinician to look for past asbestos exposure. In contrast, the search for an occupational exposure that should be routine in all cases of lung cancer, is generally more difficult because of the number of occupational aetiological factors and the absence of criteria that allow distinction of an occupational cancer from a tobacco related one. Therefore attention should be paid to the identification of occupational exposure in order to set up primary prevention programmes to prevent exposure still present in the working environment and, on the other hand, to identify the subjects entitled to the acknowledgement of occupational disease and/or to obtain the compensation available to asbestos victims.}, } @article {pmid19014568, year = {2008}, author = {Goel, A and Agrawal, A and Gupta, R and Hari, S and Dey, AB}, title = {Malignant mesothelioma of the tunica vaginalis of the testis without exposure to asbestos.}, journal = {Cases journal}, volume = {1}, number = {1}, pages = {310}, pmid = {19014568}, issn = {1757-1626}, abstract = {INTRODUCTION: Mesotheliomas are rare tumours that usually are seen in the pleura after asbestos exposure. Mesotheliomas have been reported around the testicular region but are even rarer following trauma, herniorrhaphy and long term hydrocoele.

CASE PRESENTATION: An elderly male farmer presented to us with an insidious onset of painless swelling in his left lower limb which gradually progressive. At the time of presentation it had involved his entire limb. A hard palpable mass of size 5 * 4 cms was detected in the left iliac fossa and a testicular enlargement was noted on the left side. The ultrasound of the testes showed that the left testis was enlarged 3.9*3*3.2 cms showing diffusely heterogenous echo-texture and irregular nodular surface with irregular hypoechoic thickening of the scrotal wall with left sided hydrocele. A separate hypoechoic *1.2 cms lesion was visualized in the anterior scrotal wall. FNAC from the scrotal mass showed tumour cells of simialr morphology present singly in monolayered sheets and in three dimensional fragments. The overall immunomorphological features suggested a malignant mesothelioma likely to have arisen from the tunica vaginalis.

CONCLUSION: In conclusion, though a rare tumor, malignant mesothelioma of the tunica vaginalis of the testis should be considered whenever a paratesticular mass lesion is seen even without a history of trauma or asbestos exposure as is highlighted in this case. Ultrasound findings are helpful and fine needle aspiration of the tumor may assist in arrival at a diagnosis. Surgical orchidectomy remains the modality of treatment.}, } @article {pmid18990743, year = {2008}, author = {Ugolini, D and Neri, M and Canessa, PA and Casilli, C and Catrambone, G and Ivaldi, GP and Lando, C and Marroni, P and Paganuzzi, M and Parodi, B and Visconti, P and Puntoni, R and Bonassi, S}, title = {The CREST biorepository: a tool for molecular epidemiology and translational studies on malignant mesothelioma, lung cancer, and other respiratory tract diseases.}, journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology}, volume = {17}, number = {11}, pages = {3013-3019}, doi = {10.1158/1055-9965.EPI-08-0524}, pmid = {18990743}, issn = {1055-9965}, mesh = {Biomarkers, Tumor/analysis ; Humans ; Informed Consent ; Italy/epidemiology ; Mesothelioma/*epidemiology/genetics ; *Molecular Epidemiology ; Pleural Neoplasms/*epidemiology/genetics ; Respiratory Tract Diseases/epidemiology/genetics ; Surveys and Questionnaires ; *Tissue Banks/ethics ; }, abstract = {OBJECTIVES: The Cancer of RESpiratory Tract (CREST) biorepository was established to investigate biological mechanisms and to develop tools and strategies for primary and secondary prevention of respiratory tract cancer. The CREST biorepository is focused on pleural malignant mesothelioma, a rare and severe cancer linked to asbestos exposure whose incidence is particularly high in the Ligurian region.

METHODS: The CREST biorepository includes biological specimens from (a) patients with pleural malignant mesothelioma and lung cancer, (b) patients with nonneoplastic respiratory conditions, and (c) control subjects. Whole blood, plasma, serum, lymphocytes, pleural fluid, saliva, and biopsies are collected, and a questionnaire is administered. Collection, transportation, and storage are done according to international standards.

RESULTS: As of January 31, 2008, the overall number of subjects recruited was 1,590 (446 lung cancer, 209 pleural malignant mesothelioma, and 935 controls). The biorepository includes a total of 10,055 aliquots (4,741 serum; 3,082 plasma; 1,599 whole blood; 633 pleural fluid; and 561 lymphocytes) and 107 biopsies. Demographic, clinical, and epidemiologic information is collected for each subject and processed in a dedicated database.

CONCLUSIONS: The CREST biorepository is a valuable tool for molecular epidemiology and translational studies. This structure relies on a network of contacts with local health districts that allows for an active search for patients. This is a particularly efficient approach, especially when the object of the study is a rare cancer type. The CREST experience suggests that the presence of limited resources can be overcome by the biorepository specialization, the high quality of the epidemiologic information, and the variety of samples.}, } @article {pmid18989249, year = {2008}, author = {Maniwa, Y and Yoshimura, M and Takata, M and Nishimura, Y and Ohno, Y}, title = {Effective chemotherapy based on a chemosensitivity test for malignant pleural mesothelioma.}, journal = {Annals of thoracic and cardiovascular surgery : official journal of the Association of Thoracic and Cardiovascular Surgeons of Asia}, volume = {14}, number = {5}, pages = {319-321}, pmid = {18989249}, issn = {2186-1005}, mesh = {Antineoplastic Combined Chemotherapy Protocols/pharmacology/*therapeutic use ; Cell Proliferation/drug effects ; Deoxycytidine/administration & dosage/analogs & derivatives ; Dose-Response Relationship, Drug ; *Drug Screening Assays, Antitumor ; Fatal Outcome ; Female ; Humans ; Mesothelioma/diagnosis/*drug therapy/pathology ; Middle Aged ; Neoplasm Staging ; Palliative Care ; *Patient Selection ; Pleural Neoplasms/diagnosis/*drug therapy/pathology ; Tomography, X-Ray Computed ; Tumor Cells, Cultured ; Vinblastine/administration & dosage/analogs & derivatives ; Vinorelbine ; Gemcitabine ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive and fatal tumor of the pleura and its incidence has been increasing as a result of the widespread use of asbestos worldwide. Numerous chemotherapeutic agents have been tested in many clinical trials, but the response rate does not exceed 20% for most of the investigated regimens. Here we report a case of MPM in which the chemotherapy based on the chemosensitivity test was very effective on palliation with stable disease for a long time.}, } @article {pmid18978569, year = {2008}, author = {Hillerdal, G and Sorensen, JB and Sundström, S and Riska, H and Vikström, A and Hjerpe, A}, title = {Treatment of malignant pleural mesothelioma with carboplatin, liposomized doxorubicin, and gemcitabine: a phase II study.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {3}, number = {11}, pages = {1325-1331}, doi = {10.1097/JTO.0b013e31818b174d}, pmid = {18978569}, issn = {1556-1380}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Asbestos/adverse effects ; Carboplatin/administration & dosage ; Deoxycytidine/administration & dosage/analogs & derivatives ; Disease Progression ; Doxorubicin/administration & dosage ; Female ; Humans ; Liposomes ; Male ; Maximum Tolerated Dose ; Mesothelioma/*drug therapy/pathology ; Middle Aged ; Neoplasm Staging ; Pleural Effusion, Malignant/*drug therapy/pathology ; Prognosis ; Survival Rate ; Time Factors ; Gemcitabine ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma has a poor prognosis and there is limited effect of treatment. The Nordic Mesothelioma groups decided in the year 2000 to investigate a combination of liposomized doxorubicin, carboplatin, and gemcitabine for this disease in a phase II study.

METHODS: From January 2001, to December 2003, 173 evaluable patients with biopsy-verified malignant mesothelioma were included. Two patients were lost to follow-up, but all the others were followed for at least 4 years or until death.

RESULTS: Toxicity was fairly low. There were 56 responses (32.4%), of which 2 were complete; the median time to progression was 8.6 months, and the median overall survival was 13 months. Some patients had their responses 4 to 6 months after last treatment. For 116 patients with epitheloid subtype, median survival was 17 months. A subgroup of these patients with good performance status, early stage, and age 70 years or less, showed a median survival of 22 months.

CONCLUSION: The treatment yields good results with a high number of responses and long survival, and a low toxicity. The long survival of the epitheloid subgroup with good prognostic factors is as good as or even better than some studies on "radical" surgery or multimodal treatment, underlining the need of randomized studies to evaluate such treatment options.}, } @article {pmid18958788, year = {2008}, author = {Schneider, F and Sporn, TA and Roggli, VL}, title = {Crocidolite and mesothelioma.}, journal = {Ultrastructural pathology}, volume = {32}, number = {5}, pages = {171-177}, doi = {10.1080/01913120802343848}, pmid = {18958788}, issn = {1521-0758}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos, Amosite/adverse effects/*analysis ; Asbestos, Crocidolite/adverse effects/*analysis ; Female ; Humans ; Lung/*chemistry ; Male ; Mesothelioma/*chemistry/etiology ; Middle Aged ; Mineral Fibers ; Peritoneal Neoplasms/*chemistry/etiology ; Pleural Neoplasms/*chemistry/etiology ; Registries ; }, abstract = {This study reports changes in the frequency of detection of various asbestos fiber types between 1982 and 2005. Crocidolite is increasingly detected in U.S. mesothelioma patients. The percentage of crocidolite fibers detected in lung tissue has risen from 4 to 10%, and the percentage of cases in which crocidolite was detected increased from 19 to 37%. Meanwhile, the frequency of detection of amosite and chrysotile has decreased. The authors performed a detailed analysis of cases in which crocidolite was identified in the absence of amosite. Most of such cases were identified in recent years, a finding of concern since crocidolite is considered the most potent fiber type with respect to the pathogenesis of mesothelioma.}, } @article {pmid18956802, year = {2008}, author = {Hedley-Whyte, J and Milamed, DR}, title = {Asbestos and ship-building: fatal consequences.}, journal = {The Ulster medical journal}, volume = {77}, number = {3}, pages = {191-200}, pmid = {18956802}, issn = {0041-6193}, mesh = {Asbestos/adverse effects/*history ; History, 20th Century ; Humans ; Mesothelioma/etiology/*history ; Northern Ireland ; Occupational Exposure/adverse effects/*history ; Ships/*history ; *World War II ; }, abstract = {The severe bombing of Belfast in 1941 had far-reaching consequences. Harland and Wolff was crippled. The British Merchant Ship Building Mission to the U.S.A. was being constrained by the U.K. treasury. On being told of the Belfast destruction, the British Mission and the United States Maritime Commission were emboldened. The result was 2,710 Liberty Ships launched to a British design. The necessary asbestos use associated with this and other shipbuilding, after a quarter century or more latency, is a genesis of malignancy killing thousands. Reversal of studies on asbestos limitation of fire propagation was crucial to Allied strategic planning of mass-fires which resulted in the slaughter of one to two million civilians. Boston and Belfast institutions made seminal discoveries about asbestos use and its sequelae.}, } @article {pmid18956793, year = {2008}, author = {Morrison, PJ}, title = {Asbestos, mesothelioma and the legacy of shipbuilding in Belfast.}, journal = {The Ulster medical journal}, volume = {77}, number = {3}, pages = {145}, pmid = {18956793}, issn = {0041-6193}, mesh = {Asbestos/adverse effects/*history ; History, 20th Century ; Humans ; Mesothelioma/etiology/*history ; Northern Ireland ; Occupational Exposure/adverse effects/*history ; Ships/*history ; *World War II ; }, } @article {pmid18955439, year = {2008}, author = {Patel, AV and Bogner, PN and Klippenstein, D and Ramnath, N}, title = {Malignant pleural mesothelioma after household exposure to asbestos.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {26}, number = {33}, pages = {5480-5483}, doi = {10.1200/JCO.2008.18.8268}, pmid = {18955439}, issn = {1527-7755}, mesh = {Aged ; Air Pollution, Indoor/*adverse effects ; Asbestos/*adverse effects ; Female ; Humans ; Mesothelioma/diagnosis/drug therapy/*etiology ; Pleural Neoplasms/diagnosis/drug therapy/*etiology ; }, } @article {pmid18941374, year = {2008}, author = {Teta, MJ and Mink, PJ and Lau, E and Sceurman, BK and Foster, ED}, title = {US mesothelioma patterns 1973-2002: indicators of change and insights into background rates.}, journal = {European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP)}, volume = {17}, number = {6}, pages = {525-534}, doi = {10.1097/CEJ.0b013e3282f0c0a2}, pmid = {18941374}, issn = {1473-5709}, mesh = {Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Female ; Follow-Up Studies ; Humans ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Exposure/statistics & numerical data ; Peritoneal Neoplasms/epidemiology/etiology ; Pleural Neoplasms/*epidemiology/etiology ; Sex Characteristics ; Time Factors ; United States/epidemiology ; Young Adult ; }, abstract = {Mesothelioma rates are declining toward background levels, although estimates of the background rate have varied. We expanded upon earlier analyses and provided a data-based estimate of the background rate. We analyzed US male and female patterns for five age groups using the National Cancer Institute's Surveillance Epidemiology and End Results registry data from 1973 to 2002. Age-specific and age-adjusted incidence rates per 1 000 000 persons per year, standardized to the 2000 US population, were calculated for total, pleural, and peritoneal mesothelioma. We also calculated rates for persons who attained working age after the US Occupational Safety and Health Administration asbestos exposure limits took effect. Mesothelioma rates observed among young males and females varied little over time. We observed a decline and convergence of recent male and female rates in older age groups, except those who are between the age of 60 and above, for whom the 2002 male rate was approximately five times greater than that of females. As expected, rates were higher in major shipyard areas on the West coast. Rates for persons with little or no opportunity for occupational asbestos exposure were 1.15 (95% confidence interval: 0.90-1.45) for men and 0.94 (95% confidence interval: 0.87-1.24) for women. Mesothelioma is rare in younger age groups, and rates have been relatively stable and similar for both sexes. Rates continue to decline in older age groups, but remain high for males at 60 years or older. Rates among females at older ages suggest an impact of occupational exposure. The background rate for persons below age 50 is approximately one per million, independent of sex. Future data are needed to estimate this rate for older age groups.}, } @article {pmid18940957, year = {2008}, author = {Reid, A and Heyworth, J and de Klerk, N and Musk, AW}, title = {The mortality of women exposed environmentally and domestically to blue asbestos at Wittenoom, Western Australia.}, journal = {Occupational and environmental medicine}, volume = {65}, number = {11}, pages = {743-749}, doi = {10.1136/oem.2007.035782}, pmid = {18940957}, issn = {1470-7926}, mesh = {Adolescent ; Adult ; Air Pollution, Indoor/adverse effects/analysis ; Asbestos, Crocidolite/*adverse effects/analysis ; Child ; Child, Preschool ; Environmental Exposure/*adverse effects/analysis ; Environmental Monitoring/methods ; Epidemiologic Methods ; Epidemiological Monitoring ; Female ; Housing ; Humans ; Mesothelioma/etiology/mortality ; Middle Aged ; Mining ; Neoplasms/etiology/*mortality ; Western Australia/epidemiology ; }, abstract = {OBJECTIVES: Knowledge of mortality patterns following exposure to asbestos has been determined mostly from cohort studies of men who were exposed to asbestos in their workplace. Women are more likely to have obtained their asbestos exposure domestically or from their environment.

METHODS: 2552 women and girls are documented to have lived in the blue asbestos mining and milling township of Wittenoom between 1943 and 1992 and were not involved in asbestos mining or milling. Quantitative asbestos exposure measurements were derived from periodic dust surveys undertaken in the industry and around the township. Death records were obtained for the period 1950-2004. Standardised mortality ratios (SMRs) were calculated to compare the Wittenoom women's mortality with that of the Western Australian female population.

RESULTS: There were 425 deaths, including 30 from malignant mesothelioma. There was excess mortality for all causes of death (SMR = 1.13), all neoplasms (SMR = 1.42), symptoms, signs and ill defined conditions (SMR = 6.35), lung cancer (SMR = 2.15) and pneumoconiosis (SMR = 11.8). Mortality from cancer of the ovary (SMR = 1.52), upper aerodigestive cancers (SMR = 2.70) and tuberculosis (SMR = 5.38) was increased but not significantly. The risk of death from mesothelioma was increased, but not significantly, in residents known to have lived with or washed the clothes of an Australian Blue Asbestos Company asbestos worker (HR = 2.67, 95% CI 0.77 to 9.21; HR = 2.61, 95% CI 0.85 to 7.99, respectively).

CONCLUSION: Women who were former residents of Wittenoom, exposed to asbestos in their environment or in their home, have excess cancer mortality, including mesothelioma, compared with the Western Australian female population.}, } @article {pmid18931959, year = {2007}, author = {Hu, JC and Brookings, W and Aldridge, MC}, title = {A case of solid pseudopapillary tumour of the pancreas and malignant mesothelioma.}, journal = {Journal of gastrointestinal cancer}, volume = {38}, number = {2-4}, pages = {71-73}, pmid = {18931959}, issn = {1941-6628}, mesh = {Carcinoma, Papillary/diagnostic imaging/*pathology/surgery ; Diagnosis, Differential ; Fatal Outcome ; Humans ; Liver Neoplasms/complications/secondary/surgery ; Male ; Mesothelioma/diagnostic imaging/*pathology/surgery ; Middle Aged ; Neoplasms, Second Primary/*pathology ; Pancreatectomy ; Pancreatic Neoplasms/diagnostic imaging/*pathology/surgery ; Pleural Neoplasms/diagnostic imaging/*pathology/surgery ; Tomography, X-Ray Computed ; }, abstract = {INTRODUCTION: A 59-year-old man with previous exposure to asbestos presented with dyspnoea and pleuritic chest pain, had a pleural effusion and was treated for pneumonia. His symptom recurred and was found to have an abdominal mass.

DISCUSSION: An abdominal computerised tomogram revealed pancreatic body mass arising. Pleural fluid cytology and a pleural biopsy failed to demonstrate malignancy. The pancreatic tumour was resected by distal pancreatectomy, segmental colectomy and splenectomy. The tumour was a solid pseudopapillary pancreatic tumour (SPT) with a high metastatic potential. The patient deteriorated and a repeat biopsy of the thickened pleura confirmed malignancy which was initially thought to be metastases from the SPT. Immunohistochemical staining confirmed malignant mesothelioma. The patient developed liver metastases and died 2 years from the diagnosis of metastatic disease.}, } @article {pmid18925452, year = {2009}, author = {Berry, G and Pooley, F and Gibbs, A and Harris, JM and McDonald, JC}, title = {Lung fiber burden in the Nottingham gas mask cohort.}, journal = {Inhalation toxicology}, volume = {21}, number = {2}, pages = {168-172}, doi = {10.1080/08958370802291304}, pmid = {18925452}, issn = {1091-7691}, mesh = {Air Pollutants, Occupational/*pharmacokinetics/toxicity ; Asbestos, Crocidolite/*pharmacokinetics/toxicity ; Body Burden ; Cohort Studies ; England ; Female ; Humans ; Inhalation Exposure/adverse effects/*analysis ; Lung/chemistry/*pathology ; Lung Neoplasms/chemically induced/mortality/pathology ; Male ; Mesothelioma/chemically induced/mortality/pathology ; Particle Size ; *Respiratory Protective Devices ; }, abstract = {A cohort of 1,154 employees, mainly women, who had worked 1940-1945 on the manufacture of military gas masks using filter pads containing 20% crocidolite, was traced through 2003, by which time 65 were known to have died from mesothelioma. The last known death with mesothelioma was in 1994, whereas a further 5 cases would have been expected in those with known duration of exposure. Lung tissue samples, from 50 deaths from mesothelioma and 20 other causes, had been analyzed for mineral fiber content. For ten of the mesothelioma cases data on fiber size were collected. Crocidolite fiber concentrations were analyzed in relation to exposure by time and duration. Fiber concentrations overall fell fairly steadily by decade of death, and increased with length of exposure up to 36 months and then fell sharply. The annual rate of elimination estimated by regression was 7.5% corresponding to a half life of 9.2 years. The proportion of fibers longer than 6 mum increased over time implying that the shorter fibers were eliminated more rapidly than the longer ones. The decline in concentrations with time confirms the hypothesis that crocidolite and, by inference, other amphibole fibers are slowly removed from the lung, but since the longer more carcinogenic fibers were cleared more slowly it is unclear to what extent this clearance explains the slowing down of the increase in mesothelioma mortality from about 40 years from the most recent exposure. The exact biostatistical models which most closely conform with the data remain open to question.}, } @article {pmid18843176, year = {2009}, author = {Sichletidis, L and Chloros, D and Spyratos, D and Haidich, AB and Fourkiotou, I and Kakoura, M and Patakas, D}, title = {Mortality from occupational exposure to relatively pure chrysotile: a 39-year study.}, journal = {Respiration; international review of thoracic diseases}, volume = {78}, number = {1}, pages = {63-68}, doi = {10.1159/000163443}, pmid = {18843176}, issn = {1423-0356}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asbestos, Serpentine/*toxicity ; Carcinogens, Environmental/*toxicity ; Carcinoma/mortality ; *Cause of Death ; Greece/epidemiology ; Humans ; Lung Neoplasms/epidemiology/mortality ; Male ; Mesothelioma/epidemiology ; Middle Aged ; Occupational Exposure/*adverse effects ; Prospective Studies ; Young Adult ; }, abstract = {BACKGROUND: Asbestos exposure is related to serious adverse health effects. However, there is disagreement about the relationship between chrysotile exposure and mesothelioma or lung cancer.

OBJECTIVES: Our aim was to investigate the mortality rate among workers exposed to relatively pure chrysotile in an asbestos cement factory.

PATIENTS AND METHODS: In an asbestos cement plant opened in 1968, we prospectively studied all 317 workers. A quantity of 2,000 tons of chrysotile, with minimal amphibole contamination, was used annually until 1 January 2005. Asbestos fiber concentration was measured regularly. Date and cause of death were recorded among active and retired workers.

RESULTS: Asbestos fiber concentration was always below permissible levels. Fifty-two workers died during the study. The cause was cancer in 28 subjects; lung cancer was diagnosed in 16 of them. No case of mesothelioma was reported. Death was attributed to cardiovascular diseases in 23 subjects and to liver cirrhosis in 1. Overall mortality rate was significantly lower than that of the Greek general population, standardized mortality ratio (SMR) was 0.71 (95% CI 0.53-0.93). Mortality due to cancer was increased (SMR 1.15, 95% CI 0.77-1.67), mainly due to lung cancer mortality (SMR 1.71, 95% CI 0.98-2.78), but not significantly.

CONCLUSIONS: Occupational exposure to relatively pure chrysotile within permissible levels was not associated with a significant increase in lung cancer or with mesothelioma. Decreased overall mortality of workers indicates a healthy worker effect, which--together with the relatively small cohort size--could have prevented small risks to be detected.}, } @article {pmid18840949, year = {2008}, author = {Hirose, A and Hirano, S}, title = {[Health effects of nanoparticles and nanomaterials (III). Toxicity and health effects of nanoparticles].}, journal = {Nihon eiseigaku zasshi. Japanese journal of hygiene}, volume = {63}, number = {4}, pages = {739-745}, doi = {10.1265/jjh.63.739}, pmid = {18840949}, issn = {1882-6482}, mesh = {Asbestos/toxicity ; Environmental Pollutants/*toxicity ; *Health ; Nanoparticles/*toxicity ; Nanotubes, Carbon/*toxicity ; Particle Size ; }, abstract = {As described before in the first Frontier Report of this series, there are two types of nanoparticles to be considered in hygiene science; One is the environmental nanoparticle emitted from automobiles and the other is the manufactured nanoparticle. In general nanoparticles (less than 100 nm) are reported to be permeable through cell membrane and tissues and their large surface area is responsible for the greater toxicity compared to larger particles. However, there are contradictory reports on the health effects of nanoparticles. Recent reports suggest that carbon nanotubes, fiber-shaped biopersistent nanoparticles, resemble asbestos in the pathogenesis of granuloma and mesothelioma. As such we summarize health effects of environmental and manufactured nanoparticles in the literature so far including our studies, in this report.}, } @article {pmid18838334, year = {2009}, author = {Betti, M and Neri, M and Ferrante, D and Landi, S and Biava, A and Gemignani, F and Bertolotti, M and Mirabelli, D and Padoan, M and Ugolini, D and Botta, M and Bonassi, S and Magnani, C and Dianzani, I}, title = {Pooled analysis of NAT2 genotypes as risk factors for asbestos-related malignant mesothelioma.}, journal = {International journal of hygiene and environmental health}, volume = {212}, number = {3}, pages = {322-329}, doi = {10.1016/j.ijheh.2008.08.001}, pmid = {18838334}, issn = {1618-131X}, mesh = {Acetylation ; Aged ; Arylamine N-Acetyltransferase/*genetics ; Asbestos/*adverse effects ; *Carcinogens ; Case-Control Studies ; Databases, Factual ; Female ; Finland ; *Genetic Predisposition to Disease ; Genotype ; Humans ; Italy ; Logistic Models ; Male ; Mesothelioma/chemically induced/*genetics ; Middle Aged ; Occupational Diseases/chemically induced/genetics ; Occupational Exposure/adverse effects ; Odds Ratio ; Phenotype ; Pleural Neoplasms/chemically induced/*genetics ; *Polymorphism, Genetic ; }, abstract = {Malignant mesothelioma (MM) is a rare and aggressive tumor of the pleura. The most important causal factor for the development of MM is occupational exposure to asbestos. Different lines of evidence suggest a role of genetic background in MM development, as for other cancers. Two published studies observed an association between MM and N-acetyl-transferase 2 (NAT2) polymorphisms. First, a Finnish study observed that the NAT2 slow acetylator phenotype was associated with an increased risk of MM. Conversely, MM risk was higher in Italian subjects carrying the NAT2 fast acetylator genotypes. The conflicting results obtained in Finland and Italy could be ascribed to random chance, considering the small panel of patients and controls in the two studies, but also ethnic or other differences may have been important. To ascertain the role of NAT2 genotype, we performed a study on 252 MM patients and 262 controls recruited in two Northern Italy areas that were characterized by high asbestos exposure, due to intense industrial activities (an asbestos cement factory in Casale Monferrato, mainly shipyards and refineries in Liguria). Unconditional multivariate logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). NAT2 fast acetylator genotypes showed an increased OR, although not statistically significant, both in asbestos-exposed subjects (OR=1.47; 95% CI=0.96-2.26) and in the entire population (OR=1.38; 95% CI=0.93-2.04). These results suggest that NAT2 polymorphisms do not exert a strong effect on individual susceptibility to MM.}, } @article {pmid18837886, year = {2008}, author = {Varga, C and Szendi, K}, title = {Mesothelioma and environmental exposure.}, journal = {Annals of the New York Academy of Sciences}, volume = {1138}, number = {}, pages = {73-76}, doi = {10.1196/annals.1414.012}, pmid = {18837886}, issn = {1749-6632}, mesh = {Animals ; Asbestos/*toxicity ; *Disease Models, Animal ; *Environmental Exposure ; Mesothelioma/*chemically induced ; Rats ; Rats, Wistar ; }, abstract = {A novel animal model was developed to study the direct exposure of mesothelial cells to crocidolite and chrysotile asbestos fibers. Chemically pure and pretreated Union Internationale Centre le Cancer (UICC) samples were implanted into a peritoneal envelope (Kertai's fold) of Wistar rats. Following the 12-month exposure, lack of mesothelioma induction was detected in all groups. Results suggest that the mechanism of mesothelioma formation is not a consequence of peritoneal physical exposure to the fibers.}, } @article {pmid18835652, year = {2009}, author = {Thurneysen, C and Opitz, I and Kurtz, S and Weder, W and Stahel, RA and Felley-Bosco, E}, title = {Functional inactivation of NF2/merlin in human mesothelioma.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {64}, number = {2}, pages = {140-147}, doi = {10.1016/j.lungcan.2008.08.014}, pmid = {18835652}, issn = {1872-8332}, mesh = {Adult ; Aged ; Blotting, Western ; Female ; *Gene Expression Regulation, Neoplastic ; *Genes, Neurofibromatosis 2 ; Humans ; Intracellular Signaling Peptides and Proteins ; Male ; Mesothelioma/*metabolism ; Middle Aged ; Muscle Proteins ; Neurofibromin 2/*metabolism ; Phosphoprotein Phosphatases/*metabolism ; Phosphorylation ; Polymerase Chain Reaction ; Protein Isoforms ; }, abstract = {The tumor suppressor merlin is encoded by the neurofibromatosis type 2 gene (NF2) which is located on chromosome 22q12 and mutations in this gene have been found in 40% of mesothelioma. Mutations including deletions and insertions lead to truncated and inactivated merlin. Experimental animal models indicate that disruption of the NF2 signalling pathway, together with a deficiency in ink4a, is essential for mesothelioma development. Our hypothesis was that in human mesothelioma without detectable NF2 mutations, regulators of NF2/merlin activity such as CPI-17 would be altered. CPI-17 is an oncogene inhibiting the NF2/merlin phosphatase which is necessary to maintain NF2/merlin activity. Samples obtained from 44 mesothelioma, 3 asbestosis patients and 6 normal pleura from non-asbestos related disease patients were analyzed. Truncated NF2 transcripts or presence of isoform II only were observed in 11 mesothelioma samples. In all other mesothelioma samples only NF2 isoform I or isoforms I and II were detected. 18 mesothelioma and 1 normal pleura samples also expressed splicing variant delE2/3. Unexpected variants in addition to wild-type were identified in 24 mesothelioma samples. NF2 protein was either truncated or phosphorylated on Ser 518 in primary cultures derived from 25 tumors. CPI-17 expression was significantly increased in tumor samples without deleted NF2 compared to normal pleura and tumor expressing truncated NF2. Our results support the hypothesis that the disruption of NF2 signalling is essential for the development of human mesothelioma. In tumors where no NF2 truncation can be detected, NF2 is rendered inactive by phosphorylation of Ser 518 and this can be explained at least in part by an increased expression of CPI-17.}, } @article {pmid18832552, year = {2008}, author = {van Meerbeeck, JP and Hillerdal, G}, title = {Screening for mesothelioma: more harm than good?.}, journal = {American journal of respiratory and critical care medicine}, volume = {178}, number = {8}, pages = {781-782}, doi = {10.1164/rccm.200806-955ED}, pmid = {18832552}, issn = {1535-4970}, mesh = {Asbestos/adverse effects ; Global Health ; Humans ; Mass Screening/*methods ; *Mesothelioma/diagnosis/epidemiology/etiology ; Occupational Diseases/diagnosis/epidemiology/etiology ; Occupational Exposure/adverse effects ; *Pleural Neoplasms/diagnosis/epidemiology/etiology ; Prevalence ; Prognosis ; Survival Rate ; }, } @article {pmid18828548, year = {2008}, author = {Waterman, YR}, title = {[Light and shadow of the Dutch Institute for asbestos victims].}, journal = {Epidemiologia e prevenzione}, volume = {32}, number = {3}, pages = {131-132}, pmid = {18828548}, issn = {1120-9763}, mesh = {*Asbestosis/etiology ; Humans ; *Lung Neoplasms/etiology ; *Mesothelioma/etiology ; Netherlands ; *Organizations ; *Workers' Compensation/organization & administration ; }, } @article {pmid18828547, year = {2008}, author = {Goldberg, M}, title = {[Compensating asbestos victims: the French model].}, journal = {Epidemiologia e prevenzione}, volume = {32}, number = {3}, pages = {129-131}, pmid = {18828547}, issn = {1120-9763}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Asbestosis/etiology ; France ; Humans ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Middle Aged ; Pleural Neoplasms/etiology ; Workers' Compensation/*legislation & jurisprudence ; }, } @article {pmid18826886, year = {2008}, author = {Hamilton, V}, title = {The Latrobe Valley: perspectives on asbestos issues.}, journal = {New solutions : a journal of environmental and occupational health policy : NS}, volume = {18}, number = {3}, pages = {375-378}, doi = {10.2190/NS.18.3.k}, pmid = {18826886}, issn = {1048-2911}, mesh = {Asbestos/*adverse effects ; Australia/epidemiology ; Health Services Accessibility ; Humans ; Mesothelioma/epidemiology/etiology ; *Occupational Exposure ; Patient Advocacy ; *Power Plants ; }, abstract = {The texts of two public addresses by a community advocate, Vicki Hamilton, and former asbestos worker, Geoff Swayn, are profiled in this issue's Voices section. Each articulates, in their own words, the need for continuing efforts to address the health and social impacts of Australia's ongoing asbestos disease epidemic, including the need for healing at the community and societal levels that parallel the needs of affected individuals and families. Their messages are relevant to similarly affected communities and societies internationally, particularly in relation to the need to reinvigorate societal commitment to occupational health and safety in Australia and elsewhere.}, } @article {pmid18826885, year = {2008}, author = {LaMontagne, AD and Hunter, CE and Vallance, D and Holloway, AJ}, title = {Asbestos disease in Australia: looking forward and looking back.}, journal = {New solutions : a journal of environmental and occupational health policy : NS}, volume = {18}, number = {3}, pages = {361-373}, doi = {10.2190/NS.18.3.j}, pmid = {18826885}, issn = {1048-2911}, mesh = {Anecdotes as Topic ; Asbestos/*adverse effects ; Asbestosis/*prevention & control ; Australia ; Humans ; *Public Policy ; Social Responsibility ; }, abstract = {This article provides an overview and analysis of recent developments in policy and practice in relation to asbestos disease in Australia. It complements three other concurrent publications in this issue representing important contributions of people and organizations toward addressing the health and social impacts of Australia's asbestos disease epidemic. The campaign to "Make James Hardie Pay" as well as the efforts of workers and advocates are profiled in this article as well as in this issue's Documents and Voices sections. Discussion of recent developments in asbestos-related disease research and mesothelioma surveillance is followed by articulation of the comprehensive public and social health response that is needed to fully engage and address the asbestos disease legacy and to apply lessons learned to help revive the currently waning societal commitment to occupational health and safety in Australia and elsewhere.}, } @article {pmid18824504, year = {2008}, author = {Jackaman, C and Lew, AM and Zhan, Y and Allan, JE and Koloska, B and Graham, PT and Robinson, BW and Nelson, DJ}, title = {Deliberately provoking local inflammation drives tumors to become their own protective vaccine site.}, journal = {International immunology}, volume = {20}, number = {11}, pages = {1467-1479}, doi = {10.1093/intimm/dxn104}, pmid = {18824504}, issn = {1460-2377}, mesh = {Animals ; Antibodies, Monoclonal ; Asbestos/adverse effects ; CD4-Positive T-Lymphocytes/*immunology/*metabolism/pathology ; CD40 Antigens/metabolism ; CD8-Positive T-Lymphocytes/*immunology/*metabolism/pathology ; *Cancer Vaccines ; Cell Line ; Humans ; Immunologic Memory/drug effects ; *Immunotherapy ; Injections, Intravenous ; Interleukin-2/*administration & dosage/immunology ; Lymphocyte Depletion ; Mesothelioma/immunology/therapy ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Nude ; Neoplasms, Experimental/chemically induced/immunology/therapy ; Recombinant Proteins/*administration & dosage/immunology ; }, abstract = {Anti-cancer immunotherapies aim to generate resolution of all existing tumors, including inaccessible ones, and provide long-term protection against recurrence. This is rarely achieved. Thus, we aimed to determine if the tumor microenvironment could be turned into a potent 'self'-vaccine site. Our target was to eradicate larger tumor burdens. Our models respond to single-agent immunotherapies; however, they fail at a precisely defined 'cut-off' tumor burden. Thus, this system was used to define the immune mechanisms required to mediate regression of larger tumors that are resistant to mono-immunotherapies. We report that direct injection of IL-2 with agonist anti-CD40 antibody into the tumor bed resulted in permanent resolution of treated and untreated distal tumors. Tumor-infiltrating CD8(+) T cells and neutrophils collaborated to eradicate treated tumors, IFNgamma was not critical and protective memory was preserved. This approach relied only on tumor antigens expressed within the tumor microenvironment. It also avoided systemic toxicities, did not require chemotherapy or surgery and is clinically useful because only one tumor site has to be accessible for treatment. We conclude that provoking intra-tumoral inflammation skews the tumor microenvironment from tumorigenic to immunogenic, resulting in the resolution of treated and untreated distal tumors, as well long-term protective memory.}, } @article {pmid18819151, year = {2009}, author = {Cioffredi, LA and Jänne, PA and Jackman, DM}, title = {Treatment of peritoneal mesothelioma in pediatric patients.}, journal = {Pediatric blood & cancer}, volume = {52}, number = {1}, pages = {127-129}, doi = {10.1002/pbc.21718}, pmid = {18819151}, issn = {1545-5017}, mesh = {Adolescent ; Asbestos ; Cisplatin/therapeutic use ; Disease-Free Survival ; Female ; Humans ; Male ; Mesothelioma/*drug therapy ; Peritoneal Neoplasms/*drug therapy ; Treatment Outcome ; Young Adult ; }, abstract = {Peritoneal mesothelioma is a rare and often aggressive malignancy, mostly affecting asbestos exposed adults. We present four pediatric peritoneal cases treated with a cisplatin-based doublet regimen, the standard of care in the systemic therapy of adult mesothelioma. Treatment was well tolerated, and three of these patients have achieved long-term survival. The fathers of three of the patients worked in the construction industry and may have been the source of indirect asbestos exposure.}, } @article {pmid18815631, year = {2008}, author = {Narasimhan, S and Brian, D and Khwaja, H}, title = {Acute abdomen in an asbestos factory worker.}, journal = {Canadian journal of surgery. Journal canadien de chirurgie}, volume = {51}, number = {4}, pages = {E75-6}, pmid = {18815631}, issn = {1488-2310}, mesh = {Abdomen, Acute/diagnosis/*etiology ; Aged ; Asbestosis/*complications/diagnosis ; Biopsy ; Diagnosis, Differential ; Follow-Up Studies ; Humans ; Male ; Mesothelioma/*complications/diagnosis ; Peritoneal Neoplasms/*complications/diagnosis ; Tomography, X-Ray Computed ; }, } @article {pmid18811894, year = {2008}, author = {Gogou, E and Kerenidi, T and Chamos, V and Hatzoglou, C and Gourgoulianis, KI}, title = {Environmental asbestos exposure alters the male:female ratio in patients with pleural mesothelioma.}, journal = {Respirology (Carlton, Vic.)}, volume = {13}, number = {6}, pages = {931}, doi = {10.1111/j.1440-1843.2008.01373.x}, pmid = {18811894}, issn = {1440-1843}, mesh = {Aged ; Asbestos/*toxicity ; Environmental Exposure/*adverse effects ; Female ; Humans ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Pleural Neoplasms/*epidemiology ; Turkey/epidemiology ; }, } @article {pmid18810484, year = {2009}, author = {Musti, M and Pollice, A and Cavone, D and Dragonieri, S and Bilancia, M}, title = {The relationship between malignant mesothelioma and an asbestos cement plant environmental risk: a spatial case-control study in the city of Bari (Italy).}, journal = {International archives of occupational and environmental health}, volume = {82}, number = {4}, pages = {489-497}, pmid = {18810484}, issn = {1432-1246}, mesh = {Adult ; Aged ; Aged, 80 and over ; Air Pollutants/*adverse effects ; Asbestos/*adverse effects ; Case-Control Studies ; Environmental Exposure/*adverse effects/analysis ; Female ; Geography ; Humans ; Italy/epidemiology ; Logistic Models ; Lung Neoplasms/chemically induced/*epidemiology ; Male ; Mesothelioma/chemically induced/*epidemiology ; Middle Aged ; Registries ; Residence Characteristics ; Urban Population ; }, abstract = {OBJECTIVES: To estimate the mesothelioma risk and environmental asbestos exposure (EAE) due to an asbestos-cement plant.

METHODS: A spatial case-control study including 48 malignant mesothelioma (MM) cases occurred in the period 1993-2003 selected from the regional mesothelioma register (RMR) and 273 controls. The disease risk was estimated by means of a logistic-regression model, in which the probability of disease-occurrence is expressed as a function of the classes of distances. A non-parametric method was applied to estimate the full relative risk surface.

RESULTS: Significant MM odds ratio of 5.29 (95 CI: 1.18-23.74) was found for people living within a range up to 500 m centered on the plant. The non-parametric estimation of relative risk surface unveiled a marked peak near the plant not paralleled by the spatial distribution of controls.

CONCLUSION: Evidence of an association between mesothelioma risk and EAE is highlighted. The role played by the RMR in increasing the public health local authorities awareness is stressed.}, } @article {pmid18805882, year = {2009}, author = {Reid, A and Berry, G and Heyworth, J and de Klerk, NH and Musk, AW}, title = {Predicted mortality from malignant mesothelioma among women exposed to blue asbestos at Wittenoom, Western Australia.}, journal = {Occupational and environmental medicine}, volume = {66}, number = {3}, pages = {169-174}, doi = {10.1136/oem.2007.038315}, pmid = {18805882}, issn = {1470-7926}, mesh = {Adult ; Aged ; Air Pollution/*adverse effects ; Asbestos, Crocidolite/*toxicity ; Carcinogens/*toxicity ; Cohort Studies ; Environmental Monitoring ; Female ; Forecasting ; Humans ; Likelihood Functions ; Lung Neoplasms/mortality ; Mesothelioma/etiology/*mortality ; Middle Aged ; Occupational Diseases/etiology/*mortality ; Occupational Exposure ; Pleural Neoplasms/etiology/*mortality ; Risk Assessment/methods ; Western Australia ; }, abstract = {INTRODUCTION: Nearly 3000 women and girls were documented to have lived at the blue asbestos mining and milling town of Wittenoom in Western Australia between 1943 and 1992. Eight per cent of deaths among these women to the end of 2004 have been from malignant mesothelioma of the pleura.

AIM: To predict future mortality from mesothelioma to 2030 in this cohort.

METHODS: Mesothelioma mortality rates incorporating parameters for cumulative exposure, a power of time since first exposure and annual rates of fibre clearance from the lung were calculated from maximum likelihood estimates. These rates plus age specific mortality rates for Western Australian females incorporating an excess lung cancer risk were then applied to all Wittenoom cohort women surviving to the end of 2004, in yearly increments, to predict the future numbers of cases of mesothelioma to 2030.

RESULTS: There were 40 deaths from mesothelioma among the Wittenoom women to the end of 2004. Using a range of models that incorporate time since first exposure, competing risks from other diseases, latency periods and clearance of mesothelioma from the lungs we predict 66 (lowest estimate) to 87 (highest estimate) deaths from mesothelioma until 2030. This represents one and a half to two and a half times the number of deaths that have already occurred to the end of 2004.

CONCLUSION: The high toll from mesothelioma in this cohort of women and girls will continue well into the future.}, } @article {pmid18795165, year = {2008}, author = {Pacurari, M and Yin, XJ and Zhao, J and Ding, M and Leonard, SS and Schwegler-Berry, D and Ducatman, BS and Sbarra, D and Hoover, MD and Castranova, V and Vallyathan, V}, title = {Raw single-wall carbon nanotubes induce oxidative stress and activate MAPKs, AP-1, NF-kappaB, and Akt in normal and malignant human mesothelial cells.}, journal = {Environmental health perspectives}, volume = {116}, number = {9}, pages = {1211-1217}, pmid = {18795165}, issn = {0091-6765}, mesh = {Blotting, Western ; Comet Assay ; DNA Damage ; Enzyme Activation ; Histones/metabolism ; Humans ; Mitogen-Activated Protein Kinases/*metabolism ; NF-kappa B/*metabolism ; *Nanotubes, Carbon ; Neoplasms, Mesothelial/enzymology/*metabolism/pathology ; *Oxidative Stress ; Phosphorylation ; Proto-Oncogene Proteins c-akt/*metabolism ; Reactive Oxygen Species/metabolism ; Transcription Factor AP-1/*metabolism ; Tumor Cells, Cultured ; }, abstract = {BACKGROUND: Single-wall carbon nanotubes (SWCNTs), with their unique physicochemical and mechanical properties, have many potential new applications in medicine and industry. There has been great concern subsequent to preliminary investigations of the toxicity, biopersistence, pathogenicity, and ability of SWCNTs to translocate to subpleural areas. These results compel studies of potential interactions of SWCNTs with mesothelial cells.

OBJECTIVE: Exposure to asbestos is the primary cause of malignant mesothelioma in 80-90% of individuals who develop the disease. Because the mesothelial cells are the primary target cells of asbestos-induced molecular changes mediated through an oxidant-linked mechanism, we used normal mesothelial and malignant mesothelial cells to investigate alterations in molecular signaling in response to a commercially manufactured SWCNT.

METHODS: In the present study, we exposed mesothelial cells to SWCNTs and investigated reactive oxygen species (ROS) generation, cell viability, DNA damage, histone H2AX phosphorylation, activation of poly(ADP-ribose) polymerase 1 (PARP-1), stimulation of extracellular signal-regulated kinase (ERKs), Jun N-terminal kinases (JNKs), protein p38, and activation of activator protein-1 (AP-1), nuclear factor kappaB (NF-kappaB), and protein serine-threonine kinase (Akt).

RESULTS: Exposure to SWCNTs induced ROS generation, increased cell death, enhanced DNA damage and H2AX phosphorylation, and activated PARP, AP-1, NF-kappaB, p38, and Akt in a dose-dependent manner. These events recapitulate some of the key molecular events involved in mesothelioma development associated with asbestos exposure.

CONCLUSIONS: The cellular and molecular findings reported here do suggest that SWCNTs can cause potentially adverse cellular responses in mesothelial cells through activation of molecular signaling associated with oxidative stress, which is of sufficient significance to warrant in vivo animal exposure studies.}, } @article {pmid18795123, year = {2008}, author = {Yuan, BZ and Chapman, JA and Reynolds, SH}, title = {Proteasome Inhibitor MG132 Induces Apoptosis and Inhibits Invasion of Human Malignant Pleural Mesothelioma Cells.}, journal = {Translational oncology}, volume = {1}, number = {3}, pages = {129-140}, pmid = {18795123}, issn = {1936-5233}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive malignancy tightly associated with asbestos exposure. The increasing incidence of MPM and its resistance to all therapeutic modalities necessitate an urgent development of new treatments for MPM. Proteasome inhibitors (PIs) have emerged as promising agents for treating human cancers that are refractory to current chemotherapies. In this study, we characterized MG132, a commonly used PI, for its proapoptotic and anti-invasion activities in NCI-H2452 and NCI-H2052 human thoracic MPM cell lines to determine the therapeutic effect of PIs on MPM. We found that as low as 0.5 microM MG132 caused a significant apoptosis in both cell lines as evidenced by DNA damage, cleavage of poly ADP-ribose polymerase and caspases 3, 7, and 9, and mitochondrial release of Smac/DIABLO and Cytochrome c. Mitochondrial caspase activation was found to be the underlying mechanism of the MG132-induced apoptosis. Mcl-1, among the Bcl-2 and IAP (inhibitor of apoptosis protein) antiapoptotic family proteins tested, was proved to be a major inhibitor of the MG132-induced apoptosis in MPM cells. Meanwhile, subapoptotic doses of MG132 inhibited the invasion of both MPM cell lines through reducing Rac1 activity. These observations demonstrate that MG132 possesses proapoptotic and anti-invasion activities in human MPM cells, therefore encouraging further investigations on the value of PIs for treating MPM.}, } @article {pmid18792097, year = {2009}, author = {Montanaro, F and Rosato, R and Gangemi, M and Roberti, S and Ricceri, F and Merler, E and Gennaro, V and Romanelli, A and Chellini, E and Pascucci, C and Musti, M and Nicita, C and Barbieri, PG and Marinaccio, A and Magnani, C and Mirabelli, D}, title = {Survival of pleural malignant mesothelioma in Italy: a population-based study.}, journal = {International journal of cancer}, volume = {124}, number = {1}, pages = {201-207}, doi = {10.1002/ijc.23874}, pmid = {18792097}, issn = {1097-0215}, mesh = {Aged ; Female ; Humans ; Italy ; Male ; Mesothelioma/*mortality/therapy ; Middle Aged ; Multivariate Analysis ; Pleural Neoplasms/*mortality/therapy ; Prognosis ; Proportional Hazards Models ; Registries ; Treatment Outcome ; }, abstract = {A median survival time of about 9 months is generally reported among malignant pleural mesothelioma cases. Recently, better results in terms of survival and performance status have been reported in clinical trials that included highly selected patients. We describe the survival of pleural mesothelioma patients and the factors predictive of survival in an unselected, population-based setting. Pleural mesothelioma cases (4,100) registered from 1990 to 2001 by 9 Italian regional mesothelioma registries contributing to the network of the National Mesothelioma Registry were followed until December 31, 2005. Univariate (Kaplan-Meier) and multivariate (Cox proportional hazards regression) analyses of survival were carried out according to selected individual characteristics, including limited information on treatment in a subset of 578 cases. The median survival time was 9.8 months (95% confidence interval: 9.4-10.1). In multivariate analysis, younger age at diagnosis and epithelioid histotype were associated with significantly reduced hazard ratios. Positive effects of gender (women) and being diagnosed in a hospital with a thoracic surgery unit were of border-line statistical significance. No association with calendar period of diagnosis or asbestos exposure was present. Treatment was not associated with a statistically significant improvement in survival. This is the largest population-based study on survival in patients with pleural mesothelioma to date. Age and morphology were the main prognostic factors. Results regarding the effect of treatment were disappointing but may be useful to assess the future impact, at the population level, of recently introduced therapies.}, } @article {pmid18788436, year = {2008}, author = {Okuda, M and Kashio, M and Tanaka, N and Masuno, T and Kamei, J and Tsuyuguchi, I}, title = {[A case of non-tuberculous mycobacteriosis with pleurisy with a past history of dense exposure to environmental asbestos].}, journal = {Nihon Kokyuki Gakkai zasshi = the journal of the Japanese Respiratory Society}, volume = {46}, number = {8}, pages = {655-659}, pmid = {18788436}, issn = {1343-3490}, mesh = {Aged ; Asbestosis/*complications ; Diagnosis, Differential ; Humans ; Male ; Mesothelioma/*diagnosis ; *Mycobacterium avium ; Tuberculosis, Pleural/complications ; Tuberculosis, Pulmonary/*diagnosis ; }, abstract = {We report a case of non-tuberculous mycobacteriosis (NTM) with pleurisy in a 75-year-old man. The patient was admitted with a diagnosis of pneumonia. Chest radiography and CT scans revealed a tumorous shadow that increased rapidly in size despite treatment with antibiotics. Bronchoalveolar lavage fluid (BALF) disclosed numerous asbestos bodies, suggesting dense exposure and pulmonary silicosis. The tumorous chest shadow remained undiagnosed. Repeated microscopic examination of sputum and BALF revealed no acidophilic-bacilli. Diagnostic pneumonectomy was performed to further explore the nature of the tumorous shadow on chest radiography. Ziehl-Neelsen staining of excised lung tissue disclosed no acid-bacilli; however, the washed fluid of the tissue specimen showed acid-fast bacilli that were subsequently verified as M. avium by in vitro culture. The X-ray findings in our case were not consistent with NTM or specific for disease due to asbestos inhalation. A final diagnosis of NTM was confirmed via open biopsy of the lung. Our case suggests that in addition to tuberculosis, NTM should be taken into consideration as a complication of silicosis.}, } @article {pmid18775081, year = {2008}, author = {Miles, SE and Sandrini, A and Johnson, AR and Yates, DH}, title = {Clinical consequences of asbestos-related diffuse pleural thickening: A review.}, journal = {Journal of occupational medicine and toxicology (London, England)}, volume = {3}, number = {}, pages = {20}, pmid = {18775081}, issn = {1745-6673}, abstract = {Asbestos-related diffuse pleural thickening (DPT), or extensive fibrosis of the visceral pleura secondary to asbestos exposure, is increasingly common due to the large number of workers previously exposed to asbestos. It may coexist with asbestos related pleural plaques but has a distinctly different pathology. The pathogenesis of this condition as distinct from pleural plaques is gradually becoming understood. Generation of reactive oxygen and nitrogen species, profibrotic cytokines and growth factors in response to asbestos is likely to play a role in the formation of a fibrinous intrapleural matrix. Benign asbestos related pleural effusions commonly antedate the development of diffuse pleural thickening. Environmental as well as occupational exposure to asbestos may also result in pleural fibrosis, particularly in geographic areas with naturally occurring asbestiform soil minerals. Pleural disorders may also occur after household exposure. High resolution computed tomography (CT) is more sensitive and specific than chest radiography for the diagnosis of diffuse pleural thickening, and several classification systems for asbestos-related disorders have been devised. Magnetic resonance imaging and fluorodeoxyglucose positron emission tomography (PET) scanning may be useful in distinguishing between DPT and malignant mesothelioma. DPT may be associated with symptoms such as dyspnoea and chest pain. It causes a restrictive defect on lung function and may rarely result in respiratory failure and death. Treatment is primarily supportive.}, } @article {pmid18775024, year = {2008}, author = {Jiang, L and Nagai, H and Ohara, H and Hara, S and Tachibana, M and Hirano, S and Shinohara, Y and Kohyama, N and Akatsuka, S and Toyokuni, S}, title = {Characteristics and modifying factors of asbestos-induced oxidative DNA damage.}, journal = {Cancer science}, volume = {99}, number = {11}, pages = {2142-2151}, pmid = {18775024}, issn = {1349-7006}, mesh = {Animals ; Asbestos/administration & dosage/*toxicity ; Asbestos, Crocidolite/administration & dosage/toxicity ; Base Sequence ; Cell Line, Tumor ; *DNA Breaks, Double-Stranded ; *DNA Damage ; Electron Spin Resonance Spectroscopy ; HeLa Cells ; Humans ; Hydrogen Peroxide/metabolism ; Hydroxyl Radical/metabolism ; Iron/metabolism ; Liver/drug effects/pathology ; Male ; Microscopy, Video ; Molecular Sequence Data ; Oxidation-Reduction ; Rats ; Rats, Wistar ; Spleen/drug effects/pathology ; }, abstract = {Respiratory exposure to asbestos has been linked with mesothelioma in humans. However, its carcinogenic mechanism is still unclear. Here we studied the ability of chrysotile, crocidolite and amosite fibers to induce oxidative DNA damage and the modifying factors using four distinct approaches. Electron spin resonance analyses revealed that crocidolite and amosite containing high amounts of iron, but not chrysotile, catalyzed hydroxyl radical generation in the presence of H(2)O(2), which was enhanced by an iron chelator, nitrilotriacetic acid, and suppressed by desferal. Natural iron chelators, such as citrate, adenosine 5'-triphosphate and guanosine 5'-triphosphate, did not inhibit this reaction. Second, we used time-lapse video microscopy to evaluate how cells cope with asbestos fibers. RAW264.7 cells, MeT-5 A and HeLa cells engulfed asbestos fibers, which reached not only cytoplasm but also the nucleus. Third, we utilized supercoiled plasmid DNA to evaluate the ability of each asbestos to induce DNA double strand breaks (DSB). Crocidolite and amosite, but not chrysotile, induced DNA DSB in the presence of iron chelators. We cloned the fragments to identify break sites. DSB occurred preferentially within repeat sequences and between two G:C sequences. Finally, i.p. administration of each asbestos to rats induced not only formation of nuclear 8-hydroxy-2'-deoxyguanosine in the mesothelia, spleen, liver and kidney but also significant iron deposits in the spleen. Together with the established carcinogenicity of i.p. chrysotile, our data suggest that asbestos-associated catalytic iron, whether constitutional or induced by other mechanisms, plays an important role in asbestos-induced carcinogenesis and that chemoprevention may be possible through targeting the catalytic iron.}, } @article {pmid18758312, year = {2008}, author = {Ramalingam, SS and Belani, CP}, title = {Recent advances in the treatment of malignant pleural mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {3}, number = {9}, pages = {1056-1064}, doi = {10.1097/JTO.0b013e3181834f66}, pmid = {18758312}, issn = {1556-1380}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Clinical Trials as Topic ; Combined Modality Therapy ; Humans ; Immunotherapy ; Mesothelioma/pathology/*therapy ; Pleural Neoplasms/pathology/*therapy ; Radiotherapy ; }, abstract = {Malignant pleural mesothelioma clinically manifests after decades of initial exposure to etiologic agents, such as asbestos, and presents with nonspecific symptoms such as dyspnea, pain, or weight loss. In patients with limited, resectable disease, surgical therapy with extrapleural pneumonectomy or pleurectomy is recommended, although, it is unclear which approach is superior. Radiation has a limited role and is used primarily for palliation. The palliative efficacy of traditional chemotherapeutic agents and combination regimens is modest at best. The combination of cisplatin and pemetrexed, a novel multitargeted antifolate agent, is the approved "standard of care" for patients with unresectable malignant pleural mesothelioma. A number of molecularly targeted agents are currently under evaluation for mesothelioma such as the Histone deacetylase (HDAC) inhibitors that have demonstrated promising anticancer activity. Vorinostat, a small molecule inhibitor of HDAC, which targets select members of class I and II HDACs, has shown early evidence of activity and is currently being evaluated in a randomized study for patients who progress with standard therapy for advanced mesothelioma. It is hoped that the HDAC inhibitors and other novel targeted agents will pave the way for improved outcomes for patients with this disease.}, } @article {pmid18756898, year = {2008}, author = {Sarić, M and Curin, K and Varnai, VM}, title = {The role of polio-vaccine in pleural mesothelioma--an epidemiological observation.}, journal = {Collegium antropologicum}, volume = {32}, number = {2}, pages = {479-483}, pmid = {18756898}, issn = {0350-6134}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; *Drug Contamination ; Female ; Humans ; Male ; Mesothelioma/etiology/*virology ; Middle Aged ; Occupational Exposure/adverse effects ; Pleural Neoplasms/etiology/*virology ; Poliovirus Vaccines/*adverse effects ; Simian virus 40/*isolation & purification ; }, abstract = {From the Croatian Cancer Registry (period 1991-1997) 194 malignant pleural mesothelioma patients were collected. According to participation in polio vaccination mass campaign in 1961 that covered the entire Croatian population aged 3 months to 20 years, mesothelioma patients were divided in vaccinated (N=58), and non-vaccinated (N=136) subjects. Significantly higher percentage of those with a history of occupational exposure to asbestos was found in vaccinated (79%) compared to non-vaccinated group (63%). This is the opposite to what would be expected if potential SV40 contamination of polio vaccine used had a causative role in the development of the tumour. On the other hand, shorter latency period reflected by very high percentage of 45-year-old or younger mesothelioma patients in vaccinated group (15 out of 58), with all of them having a history of occupational asbestos exposure, raises a question for a possible enhancing effect of the vaccine used to asbestos exposure, if it was contaminated with SV40.}, } @article {pmid18755931, year = {2008}, author = {Hansell, A}, title = {Airborne environmental exposure to asbestos.}, journal = {American journal of respiratory and critical care medicine}, volume = {178}, number = {6}, pages = {556-557}, doi = {10.1164/rccm.200806-859ED}, pmid = {18755931}, issn = {1535-4970}, mesh = {Air Pollutants ; Asbestosis/*epidemiology ; Cluster Analysis ; Environmental Exposure ; Humans ; Japan/epidemiology ; Mesothelioma/*epidemiology ; Pleural Neoplasms/*epidemiology ; Risk Assessment ; }, } @article {pmid18728672, year = {2008}, author = {Frost, G and Harding, AH and Darnton, A and McElvenny, D and Morgan, D}, title = {Occupational exposure to asbestos and mortality among asbestos removal workers: a Poisson regression analysis.}, journal = {British journal of cancer}, volume = {99}, number = {5}, pages = {822-829}, pmid = {18728672}, issn = {1532-1827}, mesh = {Adult ; Asbestos/isolation & purification/*toxicity ; Humans ; Middle Aged ; Occupational Diseases/*mortality ; *Occupational Exposure ; Poisson Distribution ; United Kingdom/epidemiology ; }, abstract = {The asbestos industry has shifted from manufacture to stripping/removal work. The aim of this study was to investigate early indications of mortality among removal workers. The study population consisted of 31 302 stripping/removal workers in the Great Britain Asbestos Survey, followed up to December 2005. Relative risks (RR) for causes of death with elevated standardised mortality ratios (SMR) and sufficient deaths were obtained from Poisson regression. Risk factors considered included dust suppression technique, type of respirator used, hours spent stripping, smoking status and exposure length. Deaths were elevated for all causes (SMR 123, 95% CI 119-127, n=985), all cancers including lung cancer, mesothelioma, and circulatory disease. There were no significant differences between suppression techniques and respirator types. Spending more than 40 h per week stripping rather than less than 10, increased mortality risk from all causes (RR 1.4, 95% CI 1.2-1.7), circulatory disease and ischaemic heart disease. Elevated mesothelioma risks were observed for those first exposed at young ages or exposed for more than 30 years. This study is a first step in assessing long-term mortality of asbestos removal workers in relation to working practices and asbestos exposure. Further follow-up will allow the impact of recent regulations to be assessed.}, } @article {pmid18719331, year = {2008}, author = {Nagao, N and Nishikawa, K and Kiyomoto, Y and Todoroki, M and Hoshuyama, T and Takahashi, K}, title = {[Asbestos clinics and asbestos health examinations--findings from a questionnaire survey of implementing organizations].}, journal = {Sangyo eiseigaku zasshi = Journal of occupational health}, volume = {50}, number = {5}, pages = {145-151}, doi = {10.1539/sangyoeisei.e8004}, pmid = {18719331}, issn = {1349-533X}, mesh = {*Asbestos ; Asbestosis/diagnosis ; Counseling ; Environmental Exposure ; Health Services/*statistics & numerical data ; Hospitals/statistics & numerical data ; Humans ; Information Services ; Japan ; Medical History Taking ; Surveys and Questionnaires ; Workforce ; }, abstract = {In June 2005 the press reported that many former employees of a company which used asbestos, and individuals who lived near the company's factory, had been diagnosed with mesothelioma. This finding triggered concern and alarm in Japan. In response, many "asbestos clinics" were formed, and recognized medical institutions began to implement asbestos-related health examinations. We conducted a nationwide questionnaire survey to evaluate the activities in, and the challenges for, these medical institutions. We received 137 valid responses, more than half of which were from clinics and hospital-based "asbestos clinics" instigated after the "Kubota shock." Among the asbestos exposure history interviewing practices, job histories of the interviewee were prioritized, over place of residence, and possible exposure of family members. Standard questionnaires were utilized by over 70% of respondents. The practitioners reported problems with lack of manpower and evaluation of asbestos exposure. Examinees consulted attending physicians on a wide range of matters including asbestos-related diseases, asbestos exposure, and financial compensation. It is predicted that asbestos-related diseases in general, and mesothelioma in particular, will increase in the future. Accordingly, early detection and treatment should be accorded high priority. The organizations we surveyed have important roles to play. Although resources are limited, effective diagnosis and treatment are essential, and a system assisting organizations to make accurate and efficient identification of asbestos exposure hazards is imperative.}, } @article {pmid18711823, year = {2008}, author = {Müller, KM and Dernbach, AB and Neumann, V}, title = {[Mesothelioma in academics. German Bochum mesothelioma register].}, journal = {Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen}, volume = {Suppl}, number = {}, pages = {99-102}, pmid = {18711823}, issn = {0009-4722}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Cross-Sectional Studies ; Diagnosis, Differential ; *Educational Status ; Female ; Germany ; Humans ; Lung/pathology ; Male ; Mesothelioma/*epidemiology/pathology ; Middle Aged ; Occupational Diseases/*epidemiology/pathology ; Occupational Exposure/adverse effects/statistics & numerical data ; Occupations/*statistics & numerical data ; Peritoneal Neoplasms/epidemiology/pathology ; Pleura/pathology ; Pleural Neoplasms/*epidemiology/pathology ; *Registries ; }, } @article {pmid18709470, year = {2008}, author = {Yang, H and Testa, JR and Carbone, M}, title = {Mesothelioma epidemiology, carcinogenesis, and pathogenesis.}, journal = {Current treatment options in oncology}, volume = {9}, number = {2-3}, pages = {147-157}, pmid = {18709470}, issn = {1534-6277}, support = {P30-CA06927/CA/NCI NIH HHS/United States ; R01-CA106567/CA/NCI NIH HHS/United States ; P01 CA114047/CA/NCI NIH HHS/United States ; P30 CA006927-46/CA/NCI NIH HHS/United States ; P01 CA114047-01A1/CA/NCI NIH HHS/United States ; P30 CA006927/CA/NCI NIH HHS/United States ; R01 CA106567/CA/NCI NIH HHS/United States ; P01-CA114047/CA/NCI NIH HHS/United States ; }, mesh = {Asbestos/adverse effects ; Cell Transformation, Neoplastic/genetics ; Cohort Studies ; Family Health ; Female ; Humans ; Male ; Mesothelioma/*diagnosis/*epidemiology/*etiology/physiopathology ; Models, Biological ; Pedigree ; Pleural Neoplasms/*diagnosis/*epidemiology/*etiology/physiopathology ; Simian virus 40/genetics ; Tumor Necrosis Factor-alpha/metabolism ; }, abstract = {The incidence of mesothelioma has gone from almost none to the current 2500-3000 cases per year in the USA. This estimate is an extrapolation based on information available from the Surveillance, Epidemiology and End Results (SEER) Program that collects information on approximately 12% of the US population. Mesothelioma is a cancer that is linked to exposure to carcinogenic mineral fibers. Asbestos and erionite have a proven causative role; the possible role of other mineral fibers in causing mesothelioma is being investigated. Asbestos is considered the main cause of mesothelioma in the US and in the Western world. The capacity of asbestos to induce mesothelioma has been linked to its ability to cause the release of TNF-alpha (that promotes mesothelial cells survival), other cytokines and growth factors, and of mutagenic oxygen radicals from exposed mesothelial cells and nearby macrophages. Some investigators proposed that as a consequence of the regulations to prevent exposure and to forbid and/or limit the use of asbestos, the incidence of mesothelioma in the US (and in some European countries) should have started to decline before or around the year 2000, and sharply decline thereafter. Unfortunately, there are no data available yet to support this optimistic hypothesis. Simian virus 40 (SV40) infection and radiation exposure are additional causes, although their contribution to the overall incidence of mesothelioma is unknown. Recent data from several laboratories indicate that asbestos exposure and SV40 infection are co-carcinogens in causing mesothelioma in rodents and in causing malignant transformation of human mesothelial cells in tissue culture. An exciting new development comes from the discovery that genetic susceptibility to mineral fiber carcinogenesis plays a critical role in the incidence of this cancer in certain families. It is hoped that the identification of this putative mesothelioma gene will lead to novel mechanistically driven preventive and therapeutic approaches.}, } @article {pmid18705333, year = {2008}, author = {Kim, DS and Lee, SG and Jun, SY and Kim, KW and Ha, TY and Kim, KK}, title = {Primary malignant mesothelioma developed in liver.}, journal = {Hepato-gastroenterology}, volume = {55}, number = {84}, pages = {1081-1084}, pmid = {18705333}, issn = {0172-6390}, mesh = {Angiography ; Biomarkers, Tumor/analysis ; Calbindin 2 ; Catheter Ablation ; Female ; Follow-Up Studies ; Humans ; Keratins/analysis ; Liver Neoplasms/blood supply/diagnostic imaging/pathology/*surgery ; Mesothelioma/blood supply/diagnostic imaging/pathology/*surgery ; Middle Aged ; Neoplasm Recurrence, Local/surgery ; Reoperation ; S100 Calcium Binding Protein G/analysis ; Tomography, X-Ray Computed ; }, abstract = {The following reports a rare case of primary localized malignant mesothelioma of the liver. A 53-year-old man with no history of exposure to asbestos was admitted to our department for evaluation of incidentally detected liver mass. Computed tomography and hepatic angiogram showed a tumor at the dome of the liver, which was fed mainly through the inferior phrenic artery. The mass was resected, including a portion of the diaphragm. Microscopically, the tumor was composed of cord-like or trabecular arrangements of epithelioid cells having abundant eosinophilic cytoplasm and prominent nucleoli. Immunohistochemically, the tumor cells were strongly positive for calretinin and cytokeratin 5 and negative for hepatocyte markers. These findings were consistent with our diagnosis of epithelioid mesothelioma. A local recurrence was noted 15 months after surgery, which was treated by radiofrequency ablation. At 23 months after initial surgery, locally recurrent masses with direct invasion of the diaphragm and a solitary intrahepatic metastasis were noted, which was treated by partial excision of the diaphragm with intraoperative RFA after transarterial chemoembolization.}, } @article {pmid18689090, year = {2008}, author = {Barbieri, PG and Somigliana, A and Girelli, R and Lombardi, S and Festa, R and Silvestri, S}, title = {[Malignant mesothelioma in garment sewing-machine workers].}, journal = {La Medicina del lavoro}, volume = {99}, number = {3}, pages = {187-193}, pmid = {18689090}, issn = {0025-7818}, mesh = {Aged ; Asbestos/*adverse effects ; Equipment Design ; Female ; Humans ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Diseases/*epidemiology/etiology ; Occupational Exposure ; Peritoneal Neoplasms/*epidemiology/etiology ; Pleural Neoplasms/*epidemiology/etiology ; Registries ; Technology/instrumentation ; }, abstract = {BACKGROUND: Due to poor information collected through patient interviews, a considerable number of malignant mesothelioma (MM) cases still remain classified as "unknown" asbestos exposure in the Italian Mesotelioma Registry (Re.Na.M). At the same time, some occupational asbestos exposures, which were previously unknown, have been demonstrated in certain types of work, i.e., in agriculture and in the textile industry.

OBJECTIVES: The aim of this research was to investigate the possible past occupational exposure to asbestos in clothing workers using sewing-machines.

METHODS: The MM cases were collected from the Mesothelioma Registry of Brescia. Work histories were obtained via a standardized questionnaire. Investigations were conducted in sewing-machine maintenance workshop in order to collect information regarding the possible use of asbestos parts. In addition, the use of asbestos friction materials and the use of insulated asbestos materials was checked in the clothing divisions by interviewing the management and maintenance workers of two companies where cases of MM were observed.

RESULTS: The Mesothelioma Registry of Brescia identified and collected 10 MM cases with past work in the clothing industry: 6 used sewing-machines and 4 were self-employed tailors. The search for asbestos materials gave positive results as the use of friction materials had been widespread since the 1950's in all types of sewing-machines; in addition, asbestos materials were used to insulate some parts of the ironing equipment and the steam pipelines.

CONCLUSION: The results of this investigation suggest assigning at least "possible occupational asbestos exposure" to those cases employed in clothing manufacture since the 1950's, who used sewing-machines or pressing machines, according to the Re.Na.M guidelines. Other possible occupational exposures to asbestos in this working sector cannot be excluded; when the simple interview of patients does not reveal such exposures further investigations are needed in order to demonstrate all the possible circumstances of exposure.}, } @article {pmid18687144, year = {2008}, author = {Hevel, JM and Olson-Buelow, LC and Ganesan, B and Stevens, JR and Hardman, JP and Aust, AE}, title = {Novel functional view of the crocidolite asbestos-treated A549 human lung epithelial transcriptome reveals an intricate network of pathways with opposing functions.}, journal = {BMC genomics}, volume = {9}, number = {}, pages = {376}, pmid = {18687144}, issn = {1471-2164}, mesh = {Asbestos, Crocidolite/*toxicity ; Cell Line ; Databases, Genetic ; Epithelial Cells/drug effects/metabolism ; Gene Expression/drug effects ; Gene Expression Profiling/statistics & numerical data ; Gene Regulatory Networks/*drug effects ; Genes, p53/drug effects ; Humans ; Lung/cytology/*drug effects/*metabolism ; Oligonucleotide Array Sequence Analysis/statistics & numerical data ; }, abstract = {BACKGROUND: Although exposure to asbestos is now regulated, patients continue to be diagnosed with mesothelioma, asbestosis, fibrosis and lung carcinoma because of the long latent period between exposure and clinical disease. Asbestosis is observed in approximately 200,000 patients annually and asbestos-related deaths are estimated at 4,000 annually. Although advances have been made using single gene/gene product or pathway studies, the complexity of the response to asbestos and the many unanswered questions suggested the need for a systems biology approach. The objective of this study was to generate a comprehensive view of the transcriptional changes induced by crocidolite asbestos in A549 human lung epithelial cells.

RESULTS: A statistically robust, comprehensive data set documenting the crocidolite-induced changes in the A549 transcriptome was collected. A systems biology approach involving global observations from gene ontological analyses coupled with functional network analyses was used to explore the effects of crocidolite in the context of known molecular interactions. The analyses uniquely document a transcriptome with function-based networks in cell death, cancer, cell cycle, cellular growth, proliferation, and gene expression. These functional modules show signs of a complex interplay between signaling pathways consisting of both novel and previously described asbestos-related genes/gene products. These networks allowed for the identification of novel, putative crocidolite-related genes, leading to several new hypotheses regarding genes that are important for the asbestos response. The global analysis revealed a transcriptome that bears signatures of both apoptosis/cell death and cell survival/proliferation.

CONCLUSION: Our analyses demonstrate the power of combining a statistically robust, comprehensive dataset and a functional network genomics approach to 1) identify and explore relationships between genes of known importance 2) identify novel candidate genes, and 3) observe the complex interplay between genes/gene products that function in seemingly different processes. This study represents the first function-based global approach toward understanding the response of human lung epithelial cells to the carcinogen crocidolite. Importantly, our investigation paints a much broader landscape for the crocidolite response than was previously appreciated and reveals novel paths to study. Our graphical representations of the function-based global network will be a valuable resource to model new research findings.}, } @article {pmid18686716, year = {2008}, author = {Pedra, F and Tambellini, AT and Pereira, Bde B and da Costa, AC and de Castro, HA}, title = {Mesothelioma mortality in Brazil, 1980-2003.}, journal = {International journal of occupational and environmental health}, volume = {14}, number = {3}, pages = {170-175}, doi = {10.1179/oeh.2008.14.3.170}, pmid = {18686716}, issn = {1077-3525}, mesh = {Adolescent ; Adult ; Aged ; Brazil/epidemiology ; Child ; Child, Preschool ; Environmental Exposure ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Mesothelioma/*mortality ; Middle Aged ; Mortality/trends ; Pleural Cavity/*physiopathology ; }, abstract = {Although asbestos causes asbestosis, lung cancer, and mesothelioma, it remains widely used in Brazil, mostly in cement-fiber products. We report the Brazilian mesothelioma mortality trend 1980-2003, using records of the national System of Mortality Information of DATASUS, including all deaths with IX International Disease Classification (ICD9) codes 163.n--pleura cancer during the period 1980-1995; and ICD10 codes c45.n--mesotheliomas and c38.4--pleura cancer for the years 1996-2003. Mesothelioma mortality rates increased over the period studied, from 0.56 to 1.01 deaths per 1,000,000 [corrected] habitants. The total number of mesothelioma deaths nationwide in the period studied was 2,414; the majority (1,415) were in the Southeast region. Mortality was highest among males and people over age 65. Given the history of asbestos exposure in Brazil, our findings support the need for policies that limit or ban the use of this product.}, } @article {pmid18686274, year = {2008}, author = {Dreassi, E and Lagazio, C and Maule, MM and Magnani, C and Biggeri, A}, title = {Sensitivity analysis of the relationship between disease occurrence and distance from a putative source of pollution.}, journal = {Geospatial health}, volume = {2}, number = {2}, pages = {263-271}, doi = {10.4081/gh.2008.249}, pmid = {18686274}, issn = {1970-7096}, mesh = {Asbestos ; Bayes Theorem ; *Cluster Analysis ; Environmental Pollution/*adverse effects ; Epidemiology ; Female ; *Geography ; Humans ; Industry ; Italy/epidemiology ; Male ; *Sensitivity and Specificity ; }, abstract = {The relation between disease risk and a point source of pollution is usually investigated using distance from the source as a proxy of exposure. The analysis may be based on case-control data or on aggregated data. The definition of the function relating risk of disease and distance is critical, both in a classical and in a Bayesian framework, because the likelihood is usually very flat, even with large amounts of data. In this paper we investigate how the specification of the function relating risk of disease with distance from the source and of the prior distributions on the parameters of the function affects the results when case-control data and Bayesian methods are used. We consider different popular parametric models for the risk distance function in a Bayesian approach, comparing estimates with those derived by maximum likelihood. As an example we have analyzed the relationship between a putative source of environmental pollution (an asbestos cement plant) and the occurrence of pleural malignant mesothelioma in the area of Casale Monferrato (Italy) in 1987-1993. Risk of pleural malignant mesothelioma turns out to be strongly related to distance from the asbestos cement plant. However, as the models appeared to be sensitive to modeling choices, we suggest that any analysis of disease risk around a putative source should be integrated with a careful sensitivity analysis and possibly with prior knowledge. The choice of prior distribution is extremely important and should be based on epidemiological considerations.}, } @article {pmid18686078, year = {2008}, author = {Berman, DW and Crump, KS}, title = {A meta-analysis of asbestos-related cancer risk that addresses fiber size and mineral type.}, journal = {Critical reviews in toxicology}, volume = {38 Suppl 1}, number = {}, pages = {49-73}, doi = {10.1080/10408440802273156}, pmid = {18686078}, issn = {1547-6898}, mesh = {Asbestos, Amphibole/*toxicity ; Asbestos, Serpentine/*toxicity ; Carcinogens, Environmental/*toxicity ; Humans ; Lung Neoplasms/*chemically induced/epidemiology ; Mesothelioma/*chemically induced/epidemiology ; Occupational Exposure/adverse effects ; Risk Assessment ; }, abstract = {Quantitative estimates of the risk of lung cancer or mesothelioma in humans from asbestos exposure made by the U.S. Environmental Protection Agency (EPA) make use of estimates of potency factors based on phase-contrast microscopy (PCM) and obtained from cohorts exposed to asbestos in different occupational environments. These potency factors exhibit substantial variability. The most likely reasons for this variability appear to be differences among environments in fiber size and mineralogy not accounted for by PCM. In this article, the U.S. Environmental Protection Agency (EPA) models for asbestos-related lung cancer and mesothelioma are expanded to allow the potency of fibers to depend upon their mineralogical types and sizes. This is accomplished by positing exposure metrics composed of nonoverlapping fiber categories and assigning each category its own unique potency. These category-specific potencies are estimated in a meta-analysis that fits the expanded models to potencies for lung cancer (KL's) or mesothelioma (KM's) based on PCM that were calculated for multiple epidemiological studies in our previous paper (Berman and Crump, 2008). Epidemiological study-specific estimates of exposures to fibers in the different fiber size categories of an exposure metric are estimated using distributions for fiber size based on transmission electron microscopy (TEM) obtained from the literature and matched to the individual epidemiological studies. The fraction of total asbestos exposure in a given environment respectively represented by chrysotile and amphibole asbestos is also estimated from information in the literature for that environment. Adequate information was found to allow KL's from 15 epidemiological studies and KM's from 11 studies to be included in the meta-analysis. Since the range of exposure metrics that could be considered was severely restricted by limitations in the published TEM fiber size distributions, it was decided to focus attention on four exposure metrics distinguished by fiber width: "all widths," widths > 0.2 micro m, widths < 0.4 microm, and widths < 0.2 microm, each of which has historical relevance. Each such metric defined by width was composed of four categories of fibers: chrysotile or amphibole asbestos with lengths between 5 microm and 10 microm or longer than 10 microm. Using these metrics three parameters were estimated for lung cancer and, separately, for mesothelioma: KLA, the potency of longer (length > 10 microm) amphibole fibers; rpc, the potency of pure chrysotile (uncontaminated by amphibole) relative to amphibole asbestos; and rps, the potency of shorter fibers (5 microm < length < 10 microm) relative to longer fibers. For mesothelioma, the hypothesis that chrysotile and amphibole asbestos are equally potent (rpc = 1) was strongly rejected by every metric and the hypothesis that (pure) chrysotile is nonpotent for mesothelioma was not rejected by any metric. Best estimates for the relative potency of chrysotile ranged from zero to about 1/200th that of amphibole asbestos (depending on metric). For lung cancer, the hypothesis that chrysotile and amphibole asbestos are equally potent (rpc = 1) was rejected (p < or = .05) by the two metrics based on thin fibers (length < 0.4 microm and < 0.2 microm) but not by the metrics based on thicker fibers. The "all widths" and widths < 0.4 microm metrics provide the best fits to both the lung cancer and mesothelioma data over the other metrics evaluated, although the improvements are only marginal for lung cancer. That these two metrics provide equivalent (for mesothelioma) and nearly equivalent (for lung cancer) fits to the data suggests that the available data sets may not be sufficiently rich (in variation of exposure characteristics) to fully evaluate the effects of fiber width on potency. Compared to the metric with widths > 0.2 microm with both rps and rpc fixed at 1 (which is nominally equivalent to the traditional PCM metric), the "all widths" and widths < 0.4 microm metrics provide substantially better fits for both lung cancer and, especially, mesothelioma. Although the best estimates of the potency of shorter fibers (5 < length < 10 microm) is zero for the "all widths" and widths < 0.4 microm metrics (or a small fraction of that of longer fibers for the widths > 0.2 microm metric for mesothelioma), the hypothesis that these shorter fibers were nonpotent could not be rejected for any of these metrics. Expansion of these metrics to include a category for fibers with lengths < 5 microm did not find any consistent evidence for any potency of these shortest fibers for either lung cancer or mesothelioma. Despite the substantial improvements in fit over that provided by the traditional use of PCM, neither the "all widths" nor the widths < 0.4 microm metrics (or any of the other metrics evaluated) completely resolve the differences in potency factors estimated in different occupational studies. Unresolved in particular is the discrepancy in potency factors for lung cancer from Quebec chrysotile miners and workers at the Charleston, SC, textile mill, which mainly processed chrysotile from Quebec. A leading hypothesis for this discrepancy is limitations in the fiber size distributions available for this analysis. Dement et al. (2007) recently analyzed by TEM archived air samples from the South Carolina plant to determine a detailed distribution of fiber lengths up to lengths of 40 microm and greater. If similar data become available for Quebec, perhaps these two size distributions can be used to eliminate the discrepancy between these two studies.}, } @article {pmid18680780, year = {2008}, author = {Wagner, ME and Travis, LB}, title = {Letter to the editor re: "Mesothelioma and asbestos".}, journal = {Regulatory toxicology and pharmacology : RTP}, volume = {52}, number = {3}, pages = {353-4; author reply 355}, doi = {10.1016/j.yrtph.2008.07.001}, pmid = {18680780}, issn = {1096-0295}, mesh = {Air Pollutants, Occupational/adverse effects ; Asbestos/adverse effects ; Breast Neoplasms/*radiotherapy ; Humans ; Mesothelioma/*etiology ; Radiotherapy/*adverse effects ; }, } @article {pmid18671157, year = {2008}, author = {Berman, DW and Crump, KS}, title = {Update of potency factors for asbestos-related lung cancer and mesothelioma.}, journal = {Critical reviews in toxicology}, volume = {38 Suppl 1}, number = {}, pages = {1-47}, doi = {10.1080/10408440802276167}, pmid = {18671157}, issn = {1547-6898}, mesh = {Asbestos/*toxicity ; Carcinogens, Environmental/*toxicity ; Humans ; Lung Neoplasms/*chemically induced/epidemiology ; Mesothelioma/*chemically induced/epidemiology ; Mining ; *Models, Biological ; Occupational Diseases/*chemically induced/epidemiology ; Occupational Exposure/adverse effects ; Risk Assessment ; Textiles ; United States ; United States Environmental Protection Agency ; }, abstract = {The most recent update of the U.S. Environmental Protection Agency (EPA) health assessment document for asbestos (Nicholson, 1986, referred to as "the EPA 1986 update") is now 20 years old. That document contains estimates of "potency factors" for asbestos in causing lung cancer (K(L)'s) and mesothelioma (K(M)'s) derived by fitting mathematical models to data from studies of occupational cohorts. The present paper provides a parallel analysis that incorporates data from studies published since the EPA 1986 update. The EPA lung cancer model assumes that the relative risk varies linearly with cumulative exposure lagged 10 years. This implies that the relative risk remains constant after 10 years from last exposure. The EPA mesothelioma model predicts that the mortality rate from mesothelioma increases linearly with the intensity of exposure and, for a given intensity, increases indefinitely after exposure ceases, approximately as the square of time since first exposure lagged 10 years. These assumptions were evaluated using raw data from cohorts where exposures were principally to chrysotile (South Carolina textile workers, Hein et al., 2007; mesothelioma only data from Quebec miners and millers, Liddell et al., 1997) and crocidolite (Wittenoom Gorge, Australia miners and millers, Berry et al., 2004) and using published data from a cohort exposed to amosite (Paterson, NJ, insulation manufacturers, Seidman et al., 1986). Although the linear EPA model generally provided a good description of exposure response for lung cancer, in some cases it did so only by estimating a large background risk relative to the comparison population. Some of these relative risks seem too large to be due to differences in smoking rates and are probably due at least in part to errors in exposure estimates. There was some equivocal evidence that the relative risk decreased with increasing time since last exposure in the Wittenoom cohort, but none either in the South Carolina cohort up to 50 years from last exposure or in the New Jersey cohort up to 35 years from last exposure. The mesothelioma model provided good descriptions of the observed patterns of mortality after exposure ends, with no evidence that risk increases with long times since last exposure at rates that vary from that predicted by the model (i.e., with the square of time). In particular, the model adequately described the mortality rate in Quebec chrysotile miners and millers up through >50 years from last exposure. There was statistically significant evidence in both the Wittenoom and Quebec cohorts that the exposure intensity-response is supralinear(1) rather than linear. The best-fitting models predicted that the mortality rate varies as [intensity](0.47) for Wittenoom and as [intensity](0.19) for Quebec and, in both cases, the exponent was significantly less than 1 (p< .0001). Using the EPA models, K(L)'s and K(M)'s were estimated from the three sets of raw data and also from published data covering a broader range of environments than those originally addressed in the EPA 1986 update. Uncertainty in these estimates was quantified using "uncertainty bounds" that reflect both statistical and nonstatistical uncertainties. Lung cancer potency factors (K(L)'s) were developed from 20 studies from 18 locations, compared to 13 locations covered in the EPA 1986 update. Mesothelioma potency factors (K(M)'s) were developed for 12 locations compared to four locations in the EPA 1986 update. Although the 4 locations used to calculate K(M) in the EPA 1986 update include one location with exposures to amosite and three with exposures to mixed fiber types, the 14 K(M)'s derived in the present analysis also include 6 locations in which exposures were predominantly to chrysotile and 1 where exposures were only to crocidolite. The K(M)'s showed evidence of a trend, with lowest K(M)'s obtained from cohorts exposed predominantly to chrysotile and highest K(M)'s from cohorts exposed only to amphibole asbestos, with K(M)'s from cohorts exposed to mixed fiber types being intermediate between the K(M)'s obtained from chrysotile and amphibole environments. Despite the considerable uncertainty in the K(M) estimates, the K(M) from the Quebec mines and mills was clearly smaller than those from several cohorts exposed to amphibole asbestos or a mixture of amphibole asbestos and chrysotile. For lung cancer, although there is some evidence of larger K(L)'s from amphibole asbestos exposure, there is a good deal of dispersion in the data, and one of the largest K(L)'s is from the South Carolina textile mill where exposures were almost exclusively to chrysotile. This K(L) is clearly inconsistent with the K(L) obtained from the cohort of Quebec chrysotile miners and millers. The K(L)'s and K(M)'s derived herein are defined in terms of concentrations of airborne fibers measured by phase-contrast microscopy (PCM), which only counts all structures longer than 5 microm, thicker than about 0.25 microm, and with an aspect ratio > or =3:1. Moreover, PCM does not distinguish between asbestos and nonasbestos particles. One possible reason for the discrepancies between the K(L)'s and K(M)'s from different studies is that the category of structures included in PCM counts does not correspond closely to biological activity. In the accompanying article (Berman and Crump, 2008) the K(L)'s and K(M)'s and related uncertainty bounds obtained in this article are paired with fiber size distributions from the literature obtained using transmission electron microscopy (TEM). The resulting database is used to define K(L)'s and K(M)'s that depend on both the size (e.g., length and width) and mineralogical type (e.g., chrysotile or crocidolite) of an asbestos structure. An analysis is conducted to determine how well different K(L) and K(M) definitions are able to reconcile the discrepancies observed herein among values obtained from different environments.}, } @article {pmid18670302, year = {2008}, author = {Creaney, J and Yeoman, D and Demelker, Y and Segal, A and Musk, AW and Skates, SJ and Robinson, BW}, title = {Comparison of osteopontin, megakaryocyte potentiating factor, and mesothelin proteins as markers in the serum of patients with malignant mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {3}, number = {8}, pages = {851-857}, doi = {10.1097/JTO.0b013e318180477b}, pmid = {18670302}, issn = {1556-1380}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antigens, Neoplasm/blood ; Biomarkers, Tumor/*blood ; Female ; GPI-Linked Proteins ; Humans ; Male ; Membrane Glycoproteins/*blood ; Mesothelin ; Mesothelioma/*blood ; Middle Aged ; Osteopontin/*blood ; Pleural Neoplasms/*blood ; Prognosis ; ROC Curve ; Sensitivity and Specificity ; Survival Rate ; }, abstract = {INTRODUCTION: There is increasing interest in identifying a blood-based marker for the asbestos-related tumor, malignant mesothelioma. Three potential markers for mesothelioma are mesothelin, megakaryocyte potentiating factor (MPF) and osteopontin. The purpose of the current study was to directly compare these biomarkers in the same sample population, determining their sensitivity and specificity in establishing a diagnosis, and to determine if diagnostic accuracy for mesothelioma is improved by combining the data from all three markers.

METHODS: Serum levels of mesothelin, MPF and osteopontin were determined by commercially available assays in 66 samples from patients with pleural malignant mesothelioma, 20 healthy individuals, 21 patients with asbestos-related lung or pleural disease, 30 patients presenting with benign pleural effusions and 30 patients with other malignancies.

RESULTS: Serum levels of the three markers were elevated in mesothelioma patients. At a level of specificity of 95% relative to healthy controls and patients with benign asbestos related disease, the sensitivity for mesothelioma was 34% for MPF, 47% for osteopontin and 73% for mesothelin. Osteopontin and MPF were unable to differentiate patients with mesothelioma from patients with other malignancies or those presenting with transudative pleural effusions. Combining the data from the three biomarkers using a logistic regression model did not improve sensitivity for detecting mesothelioma above that of the mesothelin marker alone.

CONCLUSION: Serum mesothelin remains the most specific marker for the diagnosis of mesothelioma.}, } @article {pmid18670171, year = {2008}, author = {Ichihara, G and Castranova, V and Tanioka, A and Miyazawa, K}, title = {Re: Induction of mesothelioma in p53+/- mouse by intraperitoneal application of multi-wall carbon nanotube.}, journal = {The Journal of toxicological sciences}, volume = {33}, number = {3}, pages = {381-2; author reply 382-4}, doi = {10.2131/jts.33.381}, pmid = {18670171}, issn = {1880-3989}, mesh = {Animals ; Asbestos/toxicity ; Genes, p53/*physiology ; Injections, Intraperitoneal ; Mesothelioma/*chemically induced ; Mice ; Nanotubes, Carbon/*toxicity ; Peritoneal Neoplasms/*chemically induced ; }, } @article {pmid20040979, year = {2008}, author = {Bianchi, C and Bianchi, T}, title = {Susceptibility and resistance in the genesis of asbestos-related mesothelioma.}, journal = {Indian journal of occupational and environmental medicine}, volume = {12}, number = {2}, pages = {57-60}, pmid = {20040979}, issn = {1998-3670}, abstract = {Asbestos is the principal agent in the etiology of malignant mesothelioma. However, a small proportion of people exposed to asbestos develop mesothelioma. This suggests the role of host factors in the genesis of the tumor. A genetic susceptibility is suggested by the occurrence of more mesothelioma cases among blood-related members of a single family. Such an occurrence reached about 4% in a large mesothelioma series. In some studies, mesothelioma patients showed higher prevalences of additional malignancies when compared with controls. This indicates a particular vulnerability to cancer in people with mesothelioma. Not rarely, very old persons heavily exposed to asbestos remain free from asbestos-related cancer, a fact indicating an absolute resistance to the oncogenic effects of asbestos. A relative resistance may be recognized in people severely exposed to asbestos who develop mesothelioma only after 60 years or more since the onset of the exposure. The long survivals, rarely observed among mesothelioma patients, have been attributed to a high efficiency of immune mechanisms. Mesotheliomas have been reported among people with severe immune impairment, such as acquired immunodeficiency syndrome patients or organ transplant recipients. The natural history of mesothelioma shows that a resistance to the oncogenic effects of asbestos does exist. Probably, such a resistance is due to the efficient immune mechanisms. To strengthen the defence mechanisms may represent a way for preventing mesothelioma among people exposed to asbestos.}, } @article {pmid18654567, year = {2008}, author = {Poland, CA and Duffin, R and Kinloch, I and Maynard, A and Wallace, WA and Seaton, A and Stone, V and Brown, S and Macnee, W and Donaldson, K}, title = {Carbon nanotubes introduced into the abdominal cavity of mice show asbestos-like pathogenicity in a pilot study.}, journal = {Nature nanotechnology}, volume = {3}, number = {7}, pages = {423-428}, doi = {10.1038/nnano.2008.111}, pmid = {18654567}, issn = {1748-3395}, mesh = {Abdominal Cavity/*pathology ; Animals ; Asbestos/*toxicity ; Asbestosis/*etiology/*pathology ; Female ; Mice ; Mice, Inbred C57BL ; Nanotubes, Carbon/*toxicity ; Pilot Projects ; }, abstract = {Carbon nanotubes have distinctive characteristics, but their needle-like fibre shape has been compared to asbestos, raising concerns that widespread use of carbon nanotubes may lead to mesothelioma, cancer of the lining of the lungs caused by exposure to asbestos. Here we show that exposing the mesothelial lining of the body cavity of mice, as a surrogate for the mesothelial lining of the chest cavity, to long multiwalled carbon nanotubes results in asbestos-like, length-dependent, pathogenic behaviour. This includes inflammation and the formation of lesions known as granulomas. This is of considerable importance, because research and business communities continue to invest heavily in carbon nanotubes for a wide range of products under the assumption that they are no more hazardous than graphite. Our results suggest the need for further research and great caution before introducing such products into the market if long-term harm is to be avoided.}, } @article {pmid18651576, year = {2008}, author = {Whitehouse, AC and Black, CB and Heppe, MS and Ruckdeschel, J and Levin, SM}, title = {Environmental exposure to Libby Asbestos and mesotheliomas.}, journal = {American journal of industrial medicine}, volume = {51}, number = {11}, pages = {877-880}, doi = {10.1002/ajim.20620}, pmid = {18651576}, issn = {1097-0274}, support = {875//PHS HHS/United States ; }, mesh = {Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Environmental Exposure/*adverse effects ; Female ; Humans ; Lung Neoplasms/*chemically induced ; Male ; Mesothelioma/*chemically induced ; Middle Aged ; Montana ; Peritoneal Neoplasms/chemically induced ; Residence Characteristics ; }, abstract = {BACKGROUND: Thirty-one cases of mesothelioma resulting from exposure to Libby Asbestos have been identified from Libby, Montana. Eleven cases not previously reported are the subject of this report.

METHODS: These cases are in non-occupationally exposed people, appearing to have resulted from exposure to contamination of the community, the surrounding forested area, and areas in proximity to the Kootenai river and railroad tracks used to haul vermiculite.

RESULTS: These exposures are considered to be of a low degree of magnitude, but are similar to those in Western Australia's crocidolite mine at Wittenoom Gorge. An epidemic of mesothelioma can likely be expected from this type of asbestos contamination over the next 20 plus years.}, } @article {pmid18646592, year = {2008}, author = {Yano, T and Morodomi, Y and Ito, K and Miura, N and Takenaka, T and Kawano, D and Shoji, F and Maehara, Y}, title = {[Treatment of malignant pleural mesothelioma--present status and future view].}, journal = {Fukuoka igaku zasshi = Hukuoka acta medica}, volume = {99}, number = {4}, pages = {74-79}, pmid = {18646592}, issn = {0016-254X}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Asbestos/adverse effects ; Clinical Trials as Topic ; Combined Modality Therapy ; Environmental Exposure/adverse effects ; *Genetic Therapy/trends ; Humans ; Immunotherapy ; Mesothelioma/diagnosis/etiology/pathology/*therapy ; Pleural Neoplasms/diagnosis/etiology/pathology/*therapy ; *Thoracic Surgical Procedures ; }, } @article {pmid18644321, year = {2008}, author = {Letonturier, P}, title = {[Asbestos: damages better known].}, journal = {Presse medicale (Paris, France : 1983)}, volume = {37}, number = {9}, pages = {1353-1354}, doi = {10.1016/j.lpm.2008.03.007}, pmid = {18644321}, issn = {2213-0276}, mesh = {Asbestos/*adverse effects ; Humans ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; Pleural Diseases/*etiology ; Pleural Neoplasms/*etiology ; }, } @article {pmid18638565, year = {2008}, author = {Amati, M and Tomasetti, M and Mariotti, L and Tarquini, LM and Valentino, M and Santarelli, L}, title = {Assessment of biomarkers in asbestos-exposed workers as indicators of cancer risk.}, journal = {Mutation research}, volume = {655}, number = {1-2}, pages = {52-58}, doi = {10.1016/j.mrgentox.2008.06.011}, pmid = {18638565}, issn = {0027-5107}, mesh = {Aged ; Asbestos/*adverse effects ; Biomarkers, Tumor/analysis/*blood ; Female ; Humans ; Lymphocytes/metabolism ; Male ; Mesothelioma/*blood/diagnosis/prevention & control ; Middle Aged ; Occupational Diseases/*blood/diagnosis/prevention & control ; *Occupational Exposure ; Pleural Neoplasms/*blood/diagnosis/prevention & control ; Regression Analysis ; Risk Factors ; }, abstract = {Epidemiological studies have shown that mortality from malignant mesothelioma (MM) and lung cancer have increased with increasing cumulative exposure to asbestos. To investigate whether tumour-related biomarkers can contribute towards the evaluation of the carcinogenic risk in populations exposed to asbestos, the DNA adduct 8-hydroxy-2'-deoxyguanosine (80HdG), interleukine-6 (IL-6), platelet-derived growth factor (PDGF-BB), hepatocyte growth factor (HGF), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGFbeta) and soluble mesothelin-related peptides (SMRPs) were analysed in a cohort of workers differently exposed to asbestos fibres at the workplace. To document biomarker levels in an unexposed population, 54 age-matched subjects were enrolled. A total of 119 subjects with a history of occupational exposure to asbestos underwent clinical examination and were interviewed by trained personnel, responding to a detailed questionnaire related to duration of asbestos exposure, smoking, and occupational task. According to the occupational tasks, asbestos-exposed subjects were analysed for their asbestos cumulative dose and the association with the biomarkers was evaluated. Among the occupational groups, maintenance workers, pipe fitters and electricians were exposed to a higher cumulative dose of asbestos fibres. Exposure to asbestos significantly increased the steady-state content of 80HdG in DNA. Elevated levels of 80HdG and IL-6 best reflected a high level of SMRPs, which is related to cell transformation. Subjects heavily exposed to asbestos [> 60(ff/cm3) x years] showed also a higher level of angiogenic factors. A combination of angiogenic biomarkers with a specific mesothelioma-biomarker such as SMRPs could be used for close surveillance of workers with a history of asbestos exposure.}, } @article {pmid18628078, year = {2008}, author = {Hasanoglu, HC and Bayram, E and Hasanoglu, A and Demirag, F}, title = {Orally ingested chrysotile asbestos affects rat lungs and pleura.}, journal = {Archives of environmental & occupational health}, volume = {63}, number = {2}, pages = {71-75}, doi = {10.3200/AEOH.63.2.71-75}, pmid = {18628078}, issn = {1933-8244}, mesh = {Administration, Oral ; Animals ; Asbestos, Serpentine/administration & dosage/*toxicity ; Lung/*drug effects/physiopathology ; Mesothelioma/chemically induced ; Pleura/*drug effects/physiopathology ; Rats ; Rats, Wistar ; Turkey ; }, abstract = {The authors designed this study to show the effects of orally ingested asbestos on the lungs and pleura. They designated 3 groups of rats: group A (n = 18) was given 1.5 g/L asbestos in water, group B (n = 18) was given 3 g/L asbestos in water, and group C (n = 15), as a control group, was given only water. Histopathological evaluation of lungs and pleura of the rats after 6 months revealed significant mesothelial proliferation and asbestos bodies. After 9 months, more rats exhibited mesothelial proliferation in group B than in group A (p < .05). The number of rats with asbestos bodies in their lungs was greater in group B than in group A. More rats in group B than in group A had asbestos in their spleen. The authors observed mesothelial proliferation in all group B rats at the end of 12 months. Ingested asbestos traveled from the gastrointestinal system to the lungs, likely via a lymphohematological route, leading to mesothelial proliferation, which may lead to malignancies.}, } @article {pmid18587319, year = {2008}, author = {Klebe, S and Mahar, A and Henderson, DW and Roggli, VL}, title = {Malignant mesothelioma with heterologous elements: clinicopathological correlation of 27 cases and literature review.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {21}, number = {9}, pages = {1084-1094}, doi = {10.1038/modpathol.2008.125}, pmid = {18587319}, issn = {1530-0285}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Chondrosarcoma/metabolism/mortality/pathology ; Diagnosis, Differential ; Female ; Humans ; Immunoenzyme Techniques ; Keratins/metabolism ; Male ; Mesothelioma/metabolism/mortality/*pathology ; Middle Aged ; Osteosarcoma/metabolism/mortality/pathology ; Peritoneal Neoplasms/metabolism/mortality/*pathology ; Pleural Neoplasms/metabolism/mortality/*pathology ; Rhabdomyosarcoma/metabolism/mortality/pathology ; Sarcoma/metabolism/mortality/*pathology ; Survival Rate ; }, abstract = {Only a small number of malignant mesotheliomas with heterologous elements have been described. There are currently no criteria for diagnosis and little data regarding prognosis. We suggest that the term heterologous mesothelioma should be reserved for tumours that show malignant heterologous elements, notably osteosarcomatous, chondrosarcomatous, or rhabdomyoblastic elements but have immunohistochemical and clinical characteristics of mesothelioma. We identified 27 such cases and characterized the clinical and pathological characteristics of these tumours. In our series, 89% originated in the pleura, and 11% from the peritoneal cavity. The median age at diagnosis was 68 years, ranging from 27 to 85 years. Of these cases, 93% occurred in males and 7% in women. Of the 27 mesothelioma cases 16 (59%) were sarcomatoid, 10 (37%) were biphasic, and one was reported as epithelioid; 40% (11 cases) showed osteosarcomatous elements only, 19% showed areas of rhabdomyosarcoma only, 19% contained areas of chondrosarcoma only, and 22% exhibited osteochondromatous elements. Immunohistochemical labelling for cytokeratins was present in the majority of cases. Exposure to asbestos was identified in all the 17 cases for which an exposure history was available (63%). Median survival was 6 months after diagnosis, similar to the survival seen in sarcomatoid mesotheliomas. The differential diagnosis includes primary and secondary pleural sarcomas, including osteosarcomas and chondrosarcomas. Immunohistochemical labelling for cytokeratins is helpful in the distinction, but lack of labelling for cytokeratins in a spindle cell/sarcomatoid tumour does not exclude the diagnosis of mesothelioma, irrespective of the presence of heterologous elements. We suggest that if the anatomical distribution conforms to that of mesothelioma, a diagnosis of heterologous mesothelioma should be made in preference to a diagnosis of primary pleural osteosarcoma or chondrosarcoma, regardless of cytokeratin positivity, as for conventional non-heterologous sarcomatoid mesothelioma.}, } @article {pmid18585424, year = {2008}, author = {Nolan, RP and Langer, AM}, title = {Rapporteur's Report Session 6: risk assessment of asbestos and other fibrous mineral particulates.}, journal = {Regulatory toxicology and pharmacology : RTP}, volume = {52}, number = {1 Suppl}, pages = {S246-8}, doi = {10.1016/j.yrtph.2008.06.002}, pmid = {18585424}, issn = {1096-0295}, mesh = {Air Pollutants, Occupational/*adverse effects/analysis/standards ; Asbestos/*adverse effects/standards ; Asbestosis/epidemiology/*etiology ; Environmental Exposure/adverse effects ; Humans ; Iron/adverse effects ; Lung Neoplasms/epidemiology/etiology ; Mesothelioma/epidemiology/etiology ; Mineral Fibers/adverse effects/standards ; *Mining ; Occupational Exposure/adverse effects/legislation & jurisprudence/standards ; Particle Size ; Particulate Matter/*adverse effects/analysis/standards ; Risk Assessment ; Silicates/adverse effects ; }, } @article {pmid18585423, year = {2008}, author = {Langer, AM}, title = {Rapporteur's Report Session 2: characterization of fibrous minerals.}, journal = {Regulatory toxicology and pharmacology : RTP}, volume = {52}, number = {1 Suppl}, pages = {S73-4}, doi = {10.1016/j.yrtph.2008.06.003}, pmid = {18585423}, issn = {1096-0295}, mesh = {Air Pollutants, Occupational/adverse effects/analysis ; Asbestos, Amphibole/analysis ; Environmental Exposure/adverse effects/*analysis ; Environmental Monitoring/methods ; Humans ; Iron/adverse effects/*analysis ; Mesothelioma/etiology ; Mineral Fibers/adverse effects/analysis ; *Mining ; Minnesota ; Occupational Exposure/adverse effects/analysis ; Risk Assessment ; Silicates/adverse effects/*analysis ; }, } @article {pmid18583923, year = {2008}, author = {Greillier, L and Astoul, P}, title = {Mesothelioma and asbestos-related pleural diseases.}, journal = {Respiration; international review of thoracic diseases}, volume = {76}, number = {1}, pages = {1-15}, doi = {10.1159/000127577}, pmid = {18583923}, issn = {1423-0356}, mesh = {*Asbestosis/diagnosis/therapy ; Humans ; *Mesothelioma/diagnosis/etiology/therapy ; *Pleural Diseases/diagnosis/etiology/therapy ; *Pleural Neoplasms/diagnosis/etiology/therapy ; }, abstract = {At present, the use of asbestos is not regulated at a worldwide scale. Moreover, there is a latency period between asbestos exposure and the manifestations of asbestos-related diseases. Consequently, pulmonologists are still dealing with consequences of asbestos exposure, which mainly occur at the pleural surface. The aim of this review is to provide an overview of asbestos-related pleural diseases. We summarized the most relevant data for the diagnosis and the management of benign asbestos pleural effusions, pleural plaques, diffuse pleural thickening and rounded atelectasis. Special attention is dedicated to malignant pleural mesothelioma, given the challenging issues of this disease, the recent advances in its management and the dynamism of research in this area.}, } @article {pmid18583574, year = {2008}, author = {Park, EK and Sandrini, A and Yates, DH and Creaney, J and Robinson, BW and Thomas, PS and Johnson, AR}, title = {Soluble mesothelin-related protein in an asbestos-exposed population: the dust diseases board cohort study.}, journal = {American journal of respiratory and critical care medicine}, volume = {178}, number = {8}, pages = {832-837}, doi = {10.1164/rccm.200802-258OC}, pmid = {18583574}, issn = {1535-4970}, mesh = {Aged ; Asbestos/*adverse effects ; Biomarkers, Tumor/blood ; Blood Proteins ; Diagnosis, Differential ; Enzyme-Linked Immunosorbent Assay ; Female ; Follow-Up Studies ; GPI-Linked Proteins ; Humans ; Male ; Mass Screening/methods ; Membrane Glycoproteins/*biosynthesis/blood ; Mesothelin ; Mesothelioma/blood/*diagnosis/etiology ; Middle Aged ; Occupational Diseases/blood/complications/*diagnosis ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/blood/*diagnosis/etiology ; Positron-Emission Tomography ; Prospective Studies ; Tomography, X-Ray Computed ; }, abstract = {RATIONALE: Soluble mesothelin-related protein (SMRP) is raised in epithelial-type malignant mesothelioma (MM), but the utility of SMRP in screening for MM is unknown.

OBJECTIVES: We aimed to evaluate SMRP in an asbestos-exposed cohort.

METHODS: A total of 538 subjects were studied. Those with elevated SMRP (> or =2.5 nM) underwent further investigation including positron emission tomography/computed tomography.

MEASUREMENTS AND MAIN RESULTS: Mean (+/-SD) SMRP in healthy subjects exposed to asbestos (n = 223) was 0.79 (+/-0.45) nM. Fifteen subjects had elevated SMRP, of whom one had lung cancer, which was successfully resected. Another with lung cancer was undetected by SMRP. No subjects were diagnosed with MM. Mean SMRP in healthy subjects was significantly lower than in subjects with pleural plaques alone (P < 0.01).

CONCLUSIONS: This is the first large-scale prospective study of SMRP for screening for malignancy in asbestos-exposed individuals. A high false-positive rate was observed. SMRP seems unlikely to prove useful in screening for MM.}, } @article {pmid18577116, year = {2008}, author = {Tsuzuki, T and Ninomiya, H and Natori, Y and Ishikawa, Y}, title = {Coalescent pleural malignant mesothelioma and adenocarcinoma of the lung, involving only minor asbestos exposure.}, journal = {Pathology international}, volume = {58}, number = {7}, pages = {451-455}, doi = {10.1111/j.1440-1827.2008.02253.x}, pmid = {18577116}, issn = {1440-1827}, mesh = {Adenocarcinoma/*pathology ; Asbestos/*adverse effects ; Humans ; Immunohistochemistry ; Lung Neoplasms/*pathology ; Male ; Mesothelioma/*pathology ; Middle Aged ; Neoplasms, Multiple Primary/*pathology ; Pleural Neoplasms/*pathology ; }, abstract = {Coexistence of pulmonary adenocarcinoma and pleural malignant mesothelioma is extremely rare, although both are asbestos-related. Herein is presented a rare case of coalescent lung tumor made up of a malignant mesothelioma and a pulmonary adenocarcinoma in a 62-year-old Japanese man, a high-school teacher with only minor asbestos exposure. Preoperative diagnosis of adenocarcinoma was made on transbronchial biopsy. At surgery, multiple small white nodules were observed on the parietal pleural surface, opposite to the lung tumor. They were confirmed to be malignant mesothelioma on histopathology of paraffin section. The pulmonary tumor mass itself consisted of two distinct portions. The major part contained papillary proliferation of hobnail and columnar cells. Peripherally, neoplastic cells grew in a lepidic fashion and micropapillary growth was also detected. The other component featured tubular structures. The former was positive for adenocarcinoma markers such as CEA, Ber-EP4, PE-10, thyroid transcription factor-1 and Napsin A, and negative for mesothelial markers including calretinin, D2-40, WT-1 and HBME, while the latter was the opposite, resulting in a diagnosis of coalescing malignant mesothelioma and adenocarcinoma. The panel of antibodies used for immunohistochemistry was useful to distinguish the two different components in the one tumor.}, } @article {pmid18573807, year = {2008}, author = {Finkelstein, MM}, title = {Asbestos fibre concentrations in the lungs of brake workers: another look.}, journal = {The Annals of occupational hygiene}, volume = {52}, number = {6}, pages = {455-461}, doi = {10.1093/annhyg/men036}, pmid = {18573807}, issn = {1475-3162}, mesh = {Asbestos/*analysis ; Data Interpretation, Statistical ; Dust/analysis ; Humans ; Lung/*chemistry ; Lung Neoplasms/chemistry/etiology ; Male ; Mesothelioma/chemistry/etiology ; Mineral Fibers/analysis ; Occupational Diseases/etiology/metabolism ; Occupational Exposure/*analysis ; }, abstract = {OBJECTIVE: To reanalyse data on the lung content of asbestos fibres among brake mechanics.

METHODS: I re-analysed data published by Butnor, Roggli and colleagues on the lung content of chrysotile and tremolite asbestos fibres among brake mechanics and controls. Statistics of the distributions were estimated by maximum likelihood to accommodate observations below the detection limit. Mean concentrations were compared by the t-test, bootstrap resampling and interval-censored survival methods.

RESULTS: The mean concentrations of fibres were higher among the brake workers than the controls. The concentration of tremolite fibres was higher than the concentration of chrysotile, a pattern similar to that observed among Quebec chrysotile miners and millers.

CONCLUSIONS: Re-analysis of published data does not support the interpretation that, in automotive brake repair workers with malignant mesothelioma, asbestos content is within the normal range. The alternative interpretation that brake mechanics have a greater than background burden of asbestos fibres, attributable to occupational exposure to dusts from friction products manufactured from Canadian chrysotile, appears more credible. This asbestos burden might be associated with an increased risk of asbestos-associated cancers.}, } @article {pmid18569099, year = {2008}, author = {Horton, DK and Bove, F and Kapil, V}, title = {Select mortality and cancer incidence among residents in various U.S. communities that received asbestos-contaminated vermiculite ore from Libby, Montana.}, journal = {Inhalation toxicology}, volume = {20}, number = {8}, pages = {767-775}, doi = {10.1080/08958370801983240}, pmid = {18569099}, issn = {1091-7691}, mesh = {Aluminum Silicates/*toxicity ; Asbestos/*toxicity ; Asbestosis/epidemiology/etiology/*mortality ; Environmental Monitoring/*methods ; Epidemiological Monitoring ; Humans ; Incidence ; *Mining ; Montana ; Neoplasms/chemically induced/*epidemiology/mortality ; United States/epidemiology ; }, abstract = {In response to the significantly elevated asbestosis mortality rates found in Libby, Montana, in 2000, this analysis evaluated whether other communities throughout the United States that received asbestos-contaminated vermiculite ore from Libby experienced similar excess rates of asbestos-related diseases. Standardized mortality ratios were calculated using state death certificates, and standardized incidence ratios were calculated using cancer registry records for populations living near facilities that processed or received Libby vermiculite. This analysis focused primarily on diseases that are directly associated with asbestos exposure (e.g., asbestosis; cancer of the peritoneum, retroperitoneum, and pleura, including mesothelioma; and mesothelioma). Lung cancer and cancers of the digestive system, also associated with asbestos exposure, were not included in the analysis because they have additional risk factors for which exposure information was not available. Data from 70 unique sites in 23 states were evaluated. No statistically significant excesses of asbestosis mortality similar to those in Libby were noted; however, 11 sites (plus a state with 6 pooled sites that were counted as 1 site) had excess rates of mesothelioma and cancer of the peritoneum, retroperitoneum, and pleura. Further investigation should be conducted at these sites with excess rates of mesothelioma and cancer of the peritoneum, retroperitoneum, and pleura by participating state health departments to determine whether exposure to Libby vermiculite might have been a contributing factor.}, } @article {pmid18569095, year = {2008}, author = {Webber, JS and Blake, DJ and Ward, TJ and Pfau, JC}, title = {Separation and characterization of respirable amphibole fibers from Libby, Montana.}, journal = {Inhalation toxicology}, volume = {20}, number = {8}, pages = {733-740}, pmid = {18569095}, issn = {1091-7691}, support = {P20 RR017670/RR/NCRR NIH HHS/United States ; P20 RR017670-10/RR/NCRR NIH HHS/United States ; P30 GM103338/GM/NIGMS NIH HHS/United States ; P20-RR017670/RR/NCRR NIH HHS/United States ; }, mesh = {Air Pollutants/chemistry/*isolation & purification ; Asbestos, Amphibole/chemistry/*isolation & purification ; *Environmental Monitoring ; Inhalation Exposure/*analysis ; Microscopy, Electron, Transmission ; *Mining ; Montana ; Particle Size ; Particulate Matter/chemistry/*isolation & purification ; Surface Properties ; }, abstract = {The vermiculite mine in Libby, Montana, was in operation for over 70 yr and was contaminated with asbestos-like amphibole fibers. The mining, processing, and shipping of this vermiculite led to significant fiber inhalation exposure throughout the community, and residents of Libby have developed numerous pulmonary diseases such as lung cancer and mesothelioma. The present study describes the separation of Libby 6-mix into respirable and nonrespirable size fractions by means of aqueous elutriation. The elutriator, designed to separate fibers with aerodynamic diameters smaller than 2.5 microm (respirable) from larger fibers, used an upward flow rate of 3.4 x 10(- 4) cm s(-1). The resultant respirable fraction constituted only 13% of the raw Libby 6-mix mass, and less than 2% of the fibers in the elutriated fraction had aerodynamic diameters exceeding 2.5 microm. Surface area of the elutriated fibers was 5.3 m(- 2) g(-1), compared to 0.53 m(-2) g(-1) for the raw fibers. There were no detectable differences in chemical composition between the larger and smaller fibers. Such harvesting of respirable fractions will allow toxicological studies to be conducted within a controlled laboratory setting, utilizing fiber sizes that may more accurately simulate historical exposure of Libby residents' lungs. Importantly, this work describes a method that allows the use of material enriched in more uniform respirable material than raw Libby 6-mix, making comparisons with other known fiber preparations more valid on a mass basis.}, } @article {pmid18561768, year = {2008}, author = {Corhay, JL and Duysinx, B and Louis, R}, title = {[Mesothelioma: a still current occupational cancer].}, journal = {Revue medicale de Liege}, volume = {63}, number = {3}, pages = {128-135}, pmid = {18561768}, issn = {0370-629X}, mesh = {Humans ; Lung Neoplasms/diagnosis/*etiology/therapy ; Mesothelioma/diagnosis/*etiology/therapy ; Occupational Diseases/diagnosis/therapy ; Occupational Exposure/*adverse effects ; }, abstract = {Mesothelioma is a rare tumour, particularly aggressive, whose incidence increases because of the massive use of asbestos during the last century. Asbestos remains indeed the principal etiologic agent of this cancer. In the event of mesothelioma it is advisable to seek an exposure, even of short duration, often which dates back to several decades. In certain circumstances compensation can be obtained at the Occupational Diseases Found. The renewed interest with regard to this tumour is supported by the improvement of mesothelioma management, the new imaging techniques, the new treatments and the broad diffusion of information related to the risk of developing this tumour following asbestos inhalation.}, } @article {pmid18560526, year = {2008}, author = {Christensen, BC and Godleski, JJ and Roelofs, CR and Longacker, JL and Bueno, R and Sugarbaker, DJ and Marsit, CJ and Nelson, HH and Kelsey, KT}, title = {Asbestos burden predicts survival in pleural mesothelioma.}, journal = {Environmental health perspectives}, volume = {116}, number = {6}, pages = {723-726}, pmid = {18560526}, issn = {0091-6765}, support = {CA126939/CA/NCI NIH HHS/United States ; P42ES05947/ES/NIEHS NIH HHS/United States ; P42 ES005947/ES/NIEHS NIH HHS/United States ; T32ES007155/ES/NIEHS NIH HHS/United States ; R01 CA126939/CA/NCI NIH HHS/United States ; T32 ES007155/ES/NIEHS NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*analysis/metabolism ; Environmental Exposure/analysis ; Female ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Lung/metabolism/pathology ; Male ; Mesothelioma/*metabolism/mortality/pathology ; Middle Aged ; Pleural Neoplasms/*metabolism/mortality/pathology ; Survival Rate ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rapidly fatal asbestos-associated malignancy with a median survival time of <1 year following diagnosis. Treatment strategy is determined in part using known prognostic factors.

OBJECTIVE: The aim of this study was to examine the relationship between asbestos exposure and survival outcome in MPM in an effort to advance the understanding of the contribution of asbestos exposure to MPM prognosis.

METHODS: We studied incident cases of MPM patients enrolled through the International Mesothelioma Program at Brigham and Women's Hospital in Boston, Massachusetts, using survival follow-up, self-reported asbestos exposure (n=128), and a subset of cases (n=80) with quantitative asbestos fiber burden measures.

RESULTS: Consistent with the established literature, we found independent, significant associations between male sex and reduced survival (p<0.04), as well as between nonepithelioid tumor histology and reduced survival (p<0.02). Although self-reported exposure to asbestos was not predictive of survival among our cases, stratifying quantitative asbestos fiber burden [number of asbestos bodies per gram of lung (wet weight)] into groups of low (0-99 asbestos bodies), moderate (100-1,099), and high fiber burden (>1,099), suggested a survival duration association among these groups (p=0.06). After adjusting for covariates in a Cox model, we found that patients with a low asbestos burden had a 3-fold elevated risk of death compared to patients with a moderate fiber burden [95% confidence interval (CI), 0.95-9.5; p=0.06], and patients with a high asbestos burden had a 4.8-fold elevated risk of death (95% CI, 1.5-15.0; p<0.01) versus those with moderate exposure.

CONCLUSION: Our data suggest that patient survival is associated with asbestos fiber burden in MPM and is perhaps modified by susceptibility.}, } @article {pmid18556631, year = {2008}, author = {Kurumatani, N and Kumagai, S}, title = {Mapping the risk of mesothelioma due to neighborhood asbestos exposure.}, journal = {American journal of respiratory and critical care medicine}, volume = {178}, number = {6}, pages = {624-629}, doi = {10.1164/rccm.200801-063OC}, pmid = {18556631}, issn = {1535-4970}, mesh = {Aged ; Air Pollutants ; Asbestos, Crocidolite ; Asbestosis/*epidemiology ; Cluster Analysis ; Dose-Response Relationship, Drug ; *Environmental Exposure ; Female ; Humans ; Japan/epidemiology ; Male ; Mesothelioma/*epidemiology/mortality ; Middle Aged ; Pleural Neoplasms/*epidemiology/mortality ; Risk Assessment ; }, abstract = {RATIONALE: Little is known about neighborhood exposure to asbestos and mesothelioma risk among residents around an industrial source of asbestos.

OBJECTIVES: To investigate the magnitude of the risk among residents by asbestos exposure levels and to determine the range of the area affected by asbestos.

METHODS: We calculated standardized mortality ratios of mesothelioma from 1995 to 2006 among the estimated population at risk that lived around a former large asbestos cement pipe plant in Amagasaki City, Japan, between 1957 and 1975, the time when the plant had used crocidolite and chrysotile. The distance between the plant and homes and relative asbestos concentrations obtained by diffusion equations involving meteorological conditions were used to determine asbestos exposure levels among residents.

MEASUREMENTS AND MAIN RESULTS: We identified 73 mesothelioma deaths of 35 men and 38 women who had no occupational exposure to asbestos. Among persons who had lived within a 300-m radius of the plant, the standardized mortality ratio of mesothelioma was 13.9 (95% confidence interval, 5.6-28.7) for men and 41.1 (95% confidence interval, 15.2-90.1) for women. When the study area was divided into five regions by relative asbestos concentration, standardized mortality ratios of mesothelioma declined, for both sexes, in a linear dose-dependent manner with concentration. The regions with a significantly elevated standardized mortality ratio reached 2,200 m from the plant in the same direction in which the wind predominantly blew.

CONCLUSIONS: Neighborhood exposure to asbestos can pose a serious risk to residents across a wide area.}, } @article {pmid18550471, year = {2008}, author = {Cappia, S and Righi, L and Mirabelli, D and Ceppi, P and Bacillo, E and Ardissone, F and Molinaro, L and Scagliotti, GV and Papotti, M}, title = {Prognostic role of osteopontin expression in malignant pleural mesothelioma.}, journal = {American journal of clinical pathology}, volume = {130}, number = {1}, pages = {58-64}, doi = {10.1309/TWCQV536WWRNEU51}, pmid = {18550471}, issn = {0002-9173}, mesh = {Aged ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; Male ; Mesothelioma/diagnosis/*metabolism/mortality ; Middle Aged ; Osteopontin/*biosynthesis ; Pleural Neoplasms/diagnosis/*metabolism/mortality ; Prognosis ; Survival Analysis ; }, abstract = {Malignant pleural mesothelioma (MPM) represents highly aggressive neoplasms with a mean survival of approximately 10 months. Osteopontin, a glycoprotein involved in cell-matrix interactions correlated with invasion and metastatic spread in several tumors, has recently been proposed as a serum marker of MPM in asbestos-exposed subjects. The aim of this study was to define the prognostic role of osteopontin in MPM. For the study, 32 long-term survivors (>24 months) and a random sample of 69 short-term survivors (or= 40 years) are, however, still untested, because of the limited follow-up of most epidemiological studies. Some authors have suggested that the increase in mesothelioma rate with TSFE might be attenuated by clearance of asbestos from the lungs. We estimated mortality time trends from pleural and peritoneal cancer in a cohort of 3,443 asbestos-cement workers, followed for more than 50 years. The functional relation between mesothelioma rate and TSFE was evaluated with various regression models. The role of asbestos clearance was explored using the traditional mesothelioma multistage model, generalized to include a term representing elimination over time. We observed 139 deaths from pleural and 56 from peritoneal cancer during the period 1950-2003. The rate of pleural cancer increased during the first 40 years of TSFE and reached a plateau thereafter. In contrast, the rate of peritoneal cancer increased monotonically with TSFE. The model allowing for asbestos elimination fitted the data better than the traditional model for pleural (p = 0.02) but not for peritoneal cancer (p = 0.22). The risk for pleural cancer, rather than showing an indefinite increase, might reach a plateau when a sufficiently long time has elapsed since exposure. The different trends for pleural and peritoneal cancer might be related to clearance of the asbestos from the workers' lungs.}, } @article {pmid18524838, year = {2008}, author = {Mirabelli, D and Calisti, R and Barone-Adesi, F and Fornero, E and Merletti, F and Magnani, C}, title = {Excess of mesotheliomas after exposure to chrysotile in Balangero, Italy.}, journal = {Occupational and environmental medicine}, volume = {65}, number = {12}, pages = {815-819}, doi = {10.1136/oem.2007.037689}, pmid = {18524838}, issn = {1470-7926}, mesh = {Aged ; Asbestos, Serpentine/*adverse effects ; Humans ; Italy/epidemiology ; Male ; Mesothelioma/epidemiology/*etiology ; Middle Aged ; Mining ; Occupational Diseases/epidemiology/*etiology ; Occupational Exposure/adverse effects/analysis ; Pleural Neoplasms/epidemiology/*etiology ; }, abstract = {BACKGROUND: Chrysotile from the mine in Balangero, Italy is considered to be free of tremolite. In a cohort study of miners and millers only two pleural cancers were reported, a finding considered to indicate that chrysotile has a low potency for inducing mesothelioma. However, follow-up ended in 1987 and white-collar workers and the employees of subcontractors were not studied.

METHODS: To complete the case ascertainment, the study searched the Registry of Malignant Mesotheliomas of Piedmont for records of cases of pleural mesothelioma among the following: mine employees; employees of subcontractors or of other firms transporting or refining Balangero asbestos, asbestos ore or mine tailings; individuals exposed to air pollution from the mine or living with mine employees; and individuals exposed to mine tailings from Balangero.

RESULTS: The study identified four new cases of pleural mesothelioma among blue-collar workers in the mine, in addition to the two reported in the cohort study. Thus, six mesotheliomas occurred, compared to the 1.5 expected (p<0.01). The study also identified three mesothelioma cases among white-collar employees at the mine, five in workers in the mine hired by subcontracting firms, and three among workers processing Balangero chrysotile outside the mine. Finally, 10 additional cases due to non-occupational exposure or exposure to re-used mine tailings were identified.

CONCLUSIONS: The cluster of 14 mesothelioma cases among workers who were active in the mine and 13 among other people exposed to Balangero chrysotile provides further evidence that tremolite-free chrysotile is carcinogenic.}, } @article {pmid18520265, year = {2008}, author = {Rivera, Z and Strianese, O and Bertino, P and Yang, H and Pass, H and Carbone, M}, title = {The relationship between simian virus 40 and mesothelioma.}, journal = {Current opinion in pulmonary medicine}, volume = {14}, number = {4}, pages = {316-321}, doi = {10.1097/MCP.0b013e3283018220}, pmid = {18520265}, issn = {1531-6971}, support = {P01 CA114047/CA/NCI NIH HHS/United States ; R01 CA092657/CA/NCI NIH HHS/United States ; R01 CA106567/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Asbestos/toxicity ; Cocarcinogenesis ; Humans ; Mesothelioma/etiology/*virology ; Pleural Neoplasms/etiology/*virology ; Simian virus 40/isolation & purification/*pathogenicity ; }, abstract = {PURPOSE OF REVIEW: Simian virus 40 is present in some human malignant mesotheliomas. The evidence in favor and against a pathogenic role of simian virus 40 in malignant mesothelioma is discussed in this review.

RECENT FINDINGS: When simian virus 40 is injected intracardially into hamsters, 60% develop and die of malignant mesothelioma. Moreover, some human malignant mesotheliomas contain and express simian virus 40 DNA and proteins. To date, over 50 laboratories have detected simian virus 40 in malignant mesotheliomas and in other tumors; however, the variability of the percentage of positivity led to a controversy about the role and significance of simian virus 40 in malignant mesotheliomas. Compared with other cell types, human mesothelial cells are unusually susceptible to simian virus 40-induced malignant transformation. The presence of simian virus 40 in malignant mesothelioma has been associated with the activation of specific oncogene pathways. Cocarcinogenesis between simian virus 40 and asbestos in causing malignant mesotheliomas has been demonstrated in three separate research laboratories using different experimental approaches. Epidemiological data possibly linking simian virus 40 and malignant mesothelioma is lacking owing to unattainable identification of infected from noninfected cohorts.

SUMMARY: Available evidence appears sufficient to link simian virus 40 either alone or in conjunction with asbestos in causing malignant mesotheliomas; however, it is still insufficient to speculate about the contribution of simian virus 40 to the overall incidence of malignant mesotheliomas.}, } @article {pmid18520263, year = {2008}, author = {Zervos, MD and Bizekis, C and Pass, HI}, title = {Malignant mesothelioma 2008.}, journal = {Current opinion in pulmonary medicine}, volume = {14}, number = {4}, pages = {303-309}, doi = {10.1097/MCP.0b013e328302851d}, pmid = {18520263}, issn = {1531-6971}, mesh = {Biomarkers, Tumor/analysis ; Clinical Trials as Topic ; Combined Modality Therapy ; Diagnostic Imaging ; Humans ; Mesothelioma/diagnosis/etiology/pathology/*therapy ; Neoplasm Staging ; Pleural Neoplasms/diagnosis/etiology/pathology/*therapy ; Prognosis ; }, abstract = {PURPOSE OF REVIEW: Mesothelioma is an aggressive malignancy of the pleura with poor survival. There will be approximately 3000 cases of mesothelioma in the United States annually. Multimodality treatment including neoadjuvant chemotherapy in selected individuals followed by extrapleural pneumonectomy and radiation has been studied in recent trials for its effects on disease free and overall survival This review provides a general overview of malignant mesothelioma with a summary of the most significant articles from within the past year as well as from the past.

RECENT FINDINGS: Areas of recent interest include the evaluation of osteopontin and mesothelin as new tumor markers for mesothelioma. New phase III trials have been performed to evaluate the use of combined chemotherapy regimens.

SUMMARY: Malignant mesothelioma is a very difficult malignancy to treat. Patients with the disease usually have an occupational asbestos exposure, and in some, viral exposure with SV40. There have been many historical treatments including combinations of local control with surgery and radiation as well as attempts to prevent systemic failure with chemotherapy. Novel therapies including intrapleural chemotherapy, photodynamic therapy and hyperthermic perfusion have also been used with some success. Finally there are several attempts at immunomodulating and targeted treatments, which are in phase I/II trials.}, } @article {pmid18517012, year = {2008}, author = {Morokawa, N and Takayanagi, N and Ubukata, M and Kurashima, K and Yoned, K and Tsuchiy, N and Miyahara, Y and Yamaguchi, S and Tokunaga, D and Saito, H and Yanagisawa, T and Sugita, Y and Kawabata, Y}, title = {[Autopsy case of diffuse pleural thickening presenting respiratory impairment and benign asbestos pleurisy].}, journal = {Nihon Kokyuki Gakkai zasshi = the journal of the Japanese Respiratory Society}, volume = {46}, number = {5}, pages = {368-373}, pmid = {18517012}, issn = {1343-3490}, mesh = {Asbestos/*adverse effects ; Autopsy ; Fatal Outcome ; Humans ; Male ; Middle Aged ; Occupational Diseases/diagnosis/*etiology/*pathology ; Occupational Exposure/*adverse effects ; Pleura/*pathology ; Pleurisy/diagnosis/*etiology/*pathology ; Respiratory Insufficiency/*etiology ; Thoracoscopy ; }, abstract = {A 51-year-old man presented with back pain in 1997. He had a 30-year-history of occupational asbestos exposure. His chest CT showed bilateral pleural thickening and pleural effusion. The pleural effusion of the right thorax exhibited both elevated level of adenosine deaminase and increased numbers of lymphocytes. Antituberculous chemotherapy had no effect on the exudates. Progressive bilateral pleural thickening were found on chest CT, and pulmonary function tests showed severe restrictive ventilatory impairments since 1998. Thoracoscopic pleural biopsy was conducted in 2001 to exclude pleural malignant mesothelioma. No malignancy was found in pleural samples. After 3-year observation and excluding other causes, he was given a diagnosis of benign asbestos pleurisy. In 2005, fibrotic changes were found in both lower lung fields in chest CT. He suffered from respiratory failure with carbon dioxide retention, and died in 2006. The autopsy disclosed asbestos-related lung diseases. We suspected that diffuse pleural thickening could be a major cause of fatal respiratory impairment in this case.}, } @article {pmid18507297, year = {2008}, author = {Payne, J and Pichora, E}, title = {Clarification on mesothelioma rates in Ontario.}, journal = {International journal of occupational and environmental health}, volume = {14}, number = {2}, pages = {157-158}, doi = {10.1179/oeh.2008.14.2.157}, pmid = {18507297}, issn = {1077-3525}, mesh = {Asbestos/*toxicity ; Humans ; Male ; Mesothelioma/*epidemiology ; Occupational Exposure ; Ontario/epidemiology ; Registries ; }, } @article {pmid18507198, year = {2008}, author = {Candura, SM and Binarelli, A and Ragno, G and Scafa, F}, title = {Two cases of asbestosis and one case of rounded atelectasis due to non-occupational asbestos exposure.}, journal = {Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace}, volume = {69}, number = {1}, pages = {35-38}, doi = {10.4081/monaldi.2008.410}, pmid = {18507198}, issn = {1122-0643}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Asbestosis/diagnosis/*etiology/therapy ; Environmental Exposure/*adverse effects ; Female ; Humans ; Italy ; Male ; Pulmonary Atelectasis/diagnosis/*etiology/therapy ; Time Factors ; }, abstract = {Asbestos is a well-known cause of several neoplastic (malignant mesothelioma, lung cancer) and non-neoplastic (asbestosis, pleuropathies) occupational diseases. Lower-level exposure in the general environment may induce pleural plaques and thickenings, and is associated with an increased mesothelioma risk. We present two patients (a 68-year-old man and a 72-year-old woman) who developed asbestosis (in association with pleural plaques and calcifications), and a 78-year-old man who developed rounded atelectasis (with pleural plaques and benign effusion), after living for several decades in the proximity of large Italian asbestos-cement plant. None of them had been exposed to asbestos occupationally. Besides living in a contaminated area, the woman used to clean the work clothes of her brother, who was employed in the local asbestos factory. The three cases indicate that non-neoplastic, long-latency asbestos-related diseases which are usually observed as a consequence of occupational exposures, may rarely develop in subjects living in contaminated geographical sites and buildings. These unusual environmental diseases raise the diagnostic problem of differentiating them from other, more common respiratory illnesses, and impose the duties of patient notification, assessment and follow-up, to assess the possibility of progression of disease and increased neoplastic risk.}, } @article {pmid18506411, year = {2008}, author = {Gräsel, B and Kaya, A and Stahl, U and Rauber, K and Kuntz, C}, title = {[Erionite-induced pleural plaques. Exposition to urban pollution in a female Turkish migrant in Germany].}, journal = {Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen}, volume = {79}, number = {6}, pages = {584-588}, pmid = {18506411}, issn = {0009-4722}, mesh = {Air Pollutants/*toxicity ; Biopsy ; Chronic Disease ; Diagnosis, Differential ; *Emigrants and Immigrants ; Female ; Humans ; Middle Aged ; Pleura/diagnostic imaging/pathology ; Pleurisy/diagnostic imaging/*etiology/pathology ; Thoracic Surgery, Video-Assisted ; Tomography, X-Ray Computed ; Turkey/ethnology ; *Urban Population ; Zeolites/*toxicity ; }, abstract = {Erionite is a zeolite mineral of volcanic origin which contains no asbestos. It is found in different regions of the world, including southeast Turkey in ash and dust, from which it can cause inflammatory pleural plaques or malignant pleural mesothelioma (MPM). We report a female Turkish migrant exposed to urban pollution in her home country who decades later suffered from pleural plaques with a nonspecific chronic inflammatory disease. The differential diagnosis of inflammatory pleural plaques was assumed radiologically and confirmed by video-assisted thoracoscopic biopsy. Short-term clinical and radiologic control of the patient will be necessary because of the risk of MPM. For epidemiologic considerations discussed referring to current literature, a growing incidence of this type of disease in migrants from high-risk areas must be reckoned with in Germany, even without exposition to asbestos.}, } @article {pmid18505080, year = {2008}, author = {Candura, SM and Canto, A and Amatu, A and Gerardini, M and Stella, G and Mensi, M and Poggi, G}, title = {Malignant mesothelioma of the tunica vaginalis testis in a petrochemical worker exposed to asbestos.}, journal = {Anticancer research}, volume = {28}, number = {2B}, pages = {1365-1368}, pmid = {18505080}, issn = {0250-7005}, mesh = {Adult ; Asbestos/*poisoning ; *Chemical Industry ; Humans ; Male ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; Occupational Exposure/*adverse effects ; Testicular Neoplasms/*etiology ; }, abstract = {Malignant mesothelioma of the tunica vaginalis testis is a rare and aggressive asbestos-related malignancy that may pose difficult diagnostic problems. After 16 years of asbestos exposure, a 38-year-old petrochemical worker came to our notice with acute right testicular pain and swelling, simulating torsion of the spermatic cord. Histopathology of surgical samples of the tunica vaginalis revealed tubulopapillary, epithelioid neoplastic proliferation. Immunohistochemical staining for the epithelial glycoprotein Ber-EP4 was negative, whereas results were positive for mesothelial markers, thus leading to the diagnosis of epithelial mesothelioma. The tumour infiltrated the testicular surface and the epididymis, but no distant metastases were found. The patient was treated with radical inguinal orchidectomy without adjuvant therapy and is free from disease 15 months after diagnosis. Tunical mesothelioma may simulate metastatic carcinoma at routine histopathological examination. Immunohistochemistry and occupational anamnesis are helpful for the correct diagnosis, which, in turn, is important for prognosis and treatment, and in relation to legal issues when asbestos is involved in the causation of the disease.}, } @article {pmid18501487, year = {2008}, author = {Gamble, JF}, title = {Rapporteur's Report Session 4: grunerite asbestos (amosite) and tremolite-ferroactinolite asbestos: risk of environmental mesothelioma.}, journal = {Regulatory toxicology and pharmacology : RTP}, volume = {52}, number = {1 Suppl}, pages = {S121-3}, doi = {10.1016/j.yrtph.2007.10.015}, pmid = {18501487}, issn = {1096-0295}, mesh = {Asbestos, Amosite/*adverse effects ; Asbestos, Amphibole/*adverse effects ; Carcinogens, Environmental/*adverse effects ; Female ; Humans ; Male ; Mediterranean Region/epidemiology ; Mesothelioma/epidemiology/*etiology ; Mineral Fibers/adverse effects ; Minnesota/epidemiology ; South Africa/epidemiology ; }, } @article {pmid18493113, year = {2008}, author = {Hosoda, Y and Hiraga, Y and Sasagawa, S}, title = {Railways and asbestos in Japan (1928-1987)--epidemiology of pleural plaques, malignancies and pneumoconioses-.}, journal = {Journal of occupational health}, volume = {50}, number = {4}, pages = {297-307}, doi = {10.1539/joh.k7002}, pmid = {18493113}, issn = {1348-9585}, mesh = {Asbestos/*adverse effects ; Humans ; Japan/epidemiology ; Lung Neoplasms/*epidemiology/physiopathology ; Male ; *Occupational Exposure ; Pleural Diseases/*epidemiology/physiopathology ; Pneumoconiosis/*epidemiology/physiopathology ; *Railroads ; }, abstract = {Asbestos has been an indispensable insulating material for railway industries, especially steam locomotives (SLs). This review (1928-1987) consists of three parts. 1) Pleural plaques: Since the 1970s, pleural plaques have been regarded as evidence of past asbestos inhalation, and more recently recognized as a risk factor of asbestos-related malignancies. For diagnostic criteria on plain radiographs, the modified ILO 1980 International Classification of Radiographs of Pneumoconioses was used. Most cases had pleural plaques with normal lungs. Large plant workers showed a significantly higher rate of plaques than workers in smaller plants. Bilateral plaques were dominant followed by the left, then the right lung, and chest wall plaques were dominant over the diaphragm. The manifestation of pleural plaques was more correlated to years since the onset of the asbestos exposure than the sum of asbestos work years, although the result was not significant. The boilermen of railway ferry steamers had a significantly higher plaque rate than other seamen. CT studies on plaques started in 1978. 2) Asbestos-related malignancies: Five retrospective cohort studies 1960-1970 were made on primary lung cancer incidence and mortality among 350,000 active railway men with smoking information. The follow-up period was 20 yr at the longest. Almost all plant workers showed a tendency of higher incidence or mortality than the controls. Two cases of mesothelioma were reported in 1980. 3) Pneumoconioses: Most studies (1928-1975) had relatively low prevalence rates among SL-related workers.}, } @article {pmid18491371, year = {2008}, author = {van Kampen, V and Merget, R and Butz, M and Taeger, D and Brüning, T}, title = {Trends in suspected and recognized occupational respiratory diseases in Germany between 1970 and 2005.}, journal = {American journal of industrial medicine}, volume = {51}, number = {7}, pages = {492-502}, doi = {10.1002/ajim.20593}, pmid = {18491371}, issn = {1097-0274}, mesh = {Female ; Germany/epidemiology ; Humans ; Incidence ; Male ; Occupational Diseases/classification/*epidemiology/*etiology ; Respiratory Tract Diseases/classification/*epidemiology/*etiology ; }, abstract = {BACKGROUND: Respiratory diseases represent a major proportion of occupational diseases in many countries. Little information is available about their incidences over the past several decades.

METHODS: Based on the reports of the three German federal accident insurance agencies, the numbers of suspected and recognized cases of occupational respiratory diseases between 1970 and 2005 were collected and combined. The trends in the rates per 100,000 insured workers were calculated.

RESULTS: In total, a decline in occupational respiratory diseases since 1998 could be observed. This trend is mainly based on the decrease in non-malignant respiratory diseases due to silica and obstructive airway diseases. In contrast, asbestos-induced diseases showed a leveling off or an increase (mesothelioma) during the last 10years.

CONCLUSIONS: Although trends in occupational disease may be influenced by several factors, the presented data indicate that prevention has been effective in reducing some ofthe most frequent occupational respiratory diseases in Germany.}, } @article {pmid18489651, year = {2008}, author = {Ikegami, Y and Kawai, N and Tozawa, K and Hayashi, Y and Kohri, K}, title = {Malignant mesothelioma of the tunica vaginalis testis related to recent asbestos.}, journal = {International journal of urology : official journal of the Japanese Urological Association}, volume = {15}, number = {6}, pages = {560-561}, doi = {10.1111/j.1442-2042.2008.02036.x}, pmid = {18489651}, issn = {1442-2042}, mesh = {Aged ; Asbestos/*adverse effects ; Fatal Outcome ; Humans ; Male ; Mesothelioma/*etiology ; Testicular Neoplasms/*etiology ; Time Factors ; }, abstract = {We report an extremely rare case of malignant mesothelioma in the tunica vaginalis testis. A 67-year-old man was referred to our hospital complaining of painless swelling in the right scrotum. Ultrasonography and computed tomography demonstrated a mass of approximately 6 cm in the right scrotum. He underwent tumor resection under a diagnosis of right intrascrotal tumor. The histopathological diagnosis was malignant mesothelioma, and he died 26 months later from multiple metastases. Asbestos may be a significant contributor to malignant mesothelioma in Japan. There have been 46 cases reported in urology departments in this country of the related symptoms, but only two of these have been clearly attributable to asbestos, which may be due to the investigations being insufficient to obtain a definitive diagnosis. In addition, this symptom is often diagnosed preoperatively as hydrocele testis; it is therefore important to carry out ultrasonography when a hydrocele testis has been diagnosed.}, } @article {pmid18488948, year = {2008}, author = {Merler, E and Marinaccio, A}, title = {[An Italian fund for the asbestos victims].}, journal = {Epidemiologia e prevenzione}, volume = {32}, number = {1}, pages = {16-17}, pmid = {18488948}, issn = {1120-9763}, mesh = {*Asbestos/adverse effects ; *Fund Raising ; Humans ; Italy ; *Mesothelioma/etiology ; }, } @article {pmid18473290, year = {2008}, author = {Neumann, V and Fischer, M and Tannapfel, A}, title = {[Carcinoid tumours of the lung and definition of the medico-legal term "lung cancer" used in the list of occupational disease in Germany--results of the German Mesothelioma Register].}, journal = {Pneumologie (Stuttgart, Germany)}, volume = {62}, number = {9}, pages = {569-573}, doi = {10.1055/s-2008-1038173}, pmid = {18473290}, issn = {1438-8790}, mesh = {Carcinoid Tumor/*classification/*epidemiology ; Germany/epidemiology ; Humans ; Lung Neoplasms/*classification/diagnosis/*epidemiology ; Occupational Diseases/*classification/*epidemiology ; Prevalence ; *Registries ; *Terminology as Topic ; }, abstract = {Carcinoid tumours are considered to be malignant epithelial tumours according to the recent WHO classification. This study is based on the examinations of tissue from 108 patients with carcinoid tumours. Our data agree with those of other studies: carcinoid tumours developed mainly in the right lung (40 %) and the lower lobe (30 %), mean age was 56 years, typical carcinoid tumours (74 %) predominated, comparatively high proportion of females (32 %), the mean latency period after asbestos exposure - assuming asbestos as one causal factor - was 35 years. A higher incidence of carcinoid tumours (1.3 %) in the collective of the mesothelioma register compared to the incidence in the collective of all lung carcinomas (1 - 2 %) was not observed. The increased pulmonary asbestos burden analysed in 26 % of patients is explained by the exposure-dependent selection of patients in the register. So far, no association between smoking habits or exposure to other, i. e., occupational pollutions and the development of carcinoid tumours could be established. In the list of occupational diseases (No. 4104) the term "lung cancer" is used without further specification. Thus the following question remains open for discussion: does the term "lung cancer" include carcinoid tumours such as malignant epithelial lung tumours, or is it restricted to the common subtypes such as small cell carcinoma, squamous cell carcinoma, adenocarcinoma, large cell carcinoma with regard to occupational disease and compensation?}, } @article {pmid18469743, year = {2008}, author = {Fry, C}, title = {Asbestos awareness.}, journal = {British dental journal}, volume = {204}, number = {9}, pages = {476-477}, doi = {10.1038/sj.bdj.2008.361}, pmid = {18469743}, issn = {1476-5373}, mesh = {Asbestosis/*complications ; Hospitals, University ; Humans ; London ; *Medical Staff, Hospital ; Mesothelioma/*etiology ; Occupational Exposure ; }, } @article {pmid18467971, year = {2008}, author = {Nagornaia, AM and Varivonchik, DV and Kundiev, IuI and Fedorenko, ZP and Gorokh, EL and Gulak, LO and Vitte, PN and Karakashian, AN and Lepeshkina, TR and Martynovskaia, TIu}, title = {[Cancer morbidity risks among workers of asbestos-cement productions].}, journal = {Meditsina truda i promyshlennaia ekologiia}, volume = {}, number = {3}, pages = {27-33}, pmid = {18467971}, issn = {1026-9428}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Asbestosis/*complications/epidemiology ; Female ; Follow-Up Studies ; Humans ; *Industry ; Male ; Middle Aged ; Morbidity/trends ; Neoplasms/*epidemiology/etiology ; Occupational Exposure/*adverse effects ; Retrospective Studies ; Survival Rate/trends ; Ukraine/epidemiology ; }, abstract = {The retrospective assessment of morbidity rates and cancer pathology risks in workers of asbestosis-cement enterprises of Ukraine has been made. It was established that annual cancer morbidity among workers makes 88,1 per 100 000 of workers (RR = 0.26, CI 95 % 0.06-1.01). The most often cancer pathology was located in digestive organs (48.1%), respiratory organs (18.5%) (lung cancer--11.1%). The mesothelioma of pleura, peritoneum and pericardium were not found. The risks (odds ratio--OR) of cancer morbidity were increased for such organs as: respiratory organs (OR = 2.37), skin (OR = 1.78), digestive organs (OR = 1.34).}, } @article {pmid18464058, year = {2008}, author = {Dodson, RF and Hammar, SP and Poye, LW}, title = {A technical comparison of evaluating asbestos concentration by phase-contrast microscopy (PCM), scanning electron microscopy (SEM), and analytical transmission electron microscopy (ATEM) as illustrated from data generated from a case report.}, journal = {Inhalation toxicology}, volume = {20}, number = {7}, pages = {723-732}, doi = {10.1080/08958370701883250}, pmid = {18464058}, issn = {1091-7691}, mesh = {Air Pollutants, Occupational/*analysis ; Asbestos, Amosite/*analysis ; Asbestos, Serpentine/*analysis ; Humans ; Lung/*ultrastructure ; Male ; Microscopy, Electron, Scanning ; Microscopy, Electron, Transmission ; Microscopy, Phase-Contrast ; Middle Aged ; Occupational Exposure/*analysis ; }, abstract = {As reported in the literature, there are more than 30 different standard methods available for the analysis of asbestos in a variety of situations. The methods include those for determining asbestos concentration in air, water, bulk building materials, surface dust, soil, and lung tissue (Millette, 2006; Dodson, 2006). Knowledge of the various methodologies is essential in determining which methodology is appropriate for any given situation. To better understand the use of various techniques in evaluating asbestos, we use an example of an individual who was a machinist in an auto supply/parts business. His work activity during much of his professional career included grinding, arcing, and drilling brake components. Asbestos has been identified as an important component of friction products, particularly brakes, and exposure to asbestos brake dust is of concern, particularly in workers where grinding, arcing, sanding, and drilling of brake components are recognized as releasing appreciable dust. Various methods can be used to evaluate asbestos in tissue and air. The case reported herein was of an individual who died from a pleural mesothelioma. Paraffin-embedded lung tissue was examined by a laboratory using scanning electron microscopy (SEM) and was reported to contain elevated asbestos body concentrations and five fibers, of which two were asbestos (one chrysotile and one tremolite). Tissue from the same paraffin block was analyzed by the laboratory of one of us (RFD) using analytical transmission electron microscopy (ATEM). While one might think the number of asbestos bodies and fibers would be similar using SEM and ATEM, this was not the case. Slightly elevated numbers of ferruginous asbestos bodies were detected in the digestate by light microscopy. Large numbers of uncoated chrysotile fibers were found by ATEM, but not by SEM. The majority of the chrysotile structures were fibrils whose detection required resolution levels attainable only at higher magnification by ATEM. The findings in this case clearly indicate that analysis of lung tissue digestates by ATEM at a higher magnification (15,000x) identifies significant numbers of asbestos fibers that are not identified by SEM at 1000x. These results further indicate that if causation of an asbestos-induced disease such as mesothelioma is based on asbestos concentration of lung tissue, erroneous conclusions can be made by analyzing tissue only by SEM. Thus, the methodologies that are available to analyze asbestos in lung tissue are extensively discussed here with respect to the type of procedure that should be utilized in various situations.}, } @article {pmid18461798, year = {2008}, author = {Kashanskiĭ, SV}, title = {[Mesothelioma in Russia: systematic review of 3576 published cases from occupational medicine viewpoint].}, journal = {Meditsina truda i promyshlennaia ekologiia}, volume = {}, number = {3}, pages = {15-21}, pmid = {18461798}, issn = {1026-9428}, mesh = {Humans ; Mesothelioma/*epidemiology/*etiology ; Morbidity/trends ; Occupational Diseases/*epidemiology/*etiology ; Occupational Exposure/*adverse effects ; *Occupational Medicine ; Russia/epidemiology ; }, abstract = {The article deals with results of systematic review of 3576 cases of mesothelioma varying in location, published over 126 years (1881-2006) in Russian. Findings are that asbestos and especially chrysotile-asbestos is not a leading and even obligate etiologic factor. The disease is polyetiologic. To restore social justice in relation to mesothelioma patients, scientists should design an algorithm connecting the disease with occupation, create national cancer register for mesothelioma, study prevalence of the disease in separate regions and in the whole country.}, } @article {pmid18459940, year = {2008}, author = {Hendrickx, M}, title = {Records of the Australian Mesothelioma Surveillance Program have been lost!.}, journal = {The Medical journal of Australia}, volume = {188}, number = {9}, pages = {552; author reply 552}, doi = {10.5694/j.1326-5377.2008.tb01785.x}, pmid = {18459940}, issn = {0025-729X}, mesh = {Asbestos/*adverse effects ; Australia/epidemiology ; Humans ; Lung Neoplasms/*epidemiology/etiology ; Mesothelioma/*epidemiology/etiology ; Occupational Diseases/*epidemiology/etiology ; *Registries ; }, } @article {pmid18454162, year = {2008}, author = {Creaney, J and Segal, A and Sterrett, G and Platten, MA and Baker, E and Murch, AR and Nowak, AK and Robinson, BW and Millward, MJ}, title = {Overexpression and altered glycosylation of MUC1 in malignant mesothelioma.}, journal = {British journal of cancer}, volume = {98}, number = {9}, pages = {1562-1569}, pmid = {18454162}, issn = {1532-1827}, mesh = {Aged ; Aged, 80 and over ; Alternative Splicing ; Biomarkers, Tumor/analysis/blood/*metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Glycosylation ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Male ; Mesothelioma/blood/chemistry/*diagnosis/*metabolism ; Middle Aged ; Mucin-1/analysis/blood/genetics/*metabolism ; Pleural Effusion, Malignant/blood/chemistry/*diagnosis/*metabolism ; Polymerase Chain Reaction ; RNA, Messenger/metabolism ; Sensitivity and Specificity ; Up-Regulation ; }, abstract = {Current interest in the MUC1/EMA mucin relates to its role in malignancy, and its potential as a therapeutic target. MUC1/EMA expression has been observed in the majority of epithelioid mesotheliomas. However, little is known of the characteristics of MUC1/EMA in mesothelioma. Herein, we studied the cell surface and soluble expression of the MUC1/EMA glycoprotein, and determined the mRNA and genomic expression profiles in mesothelioma. We found that the anti-MUC1 antibody, E29, was the most diagnostically useful of seven antibody clones examined with a sensitivity of 84% (16 out of 19 cases) and no false positive results. MUC1 mRNA expression was significantly higher in mesothelioma samples than in benign mesothelial cells. No amplification of the MUC1 gene was observed by FISH. Seven of 9 mesothelioma samples expressed MUC1-secreted mRNA isoform in addition to the archetypal MUC1/transmembrane form. CA15.3 (soluble MUC1) levels were significantly higher in the serum of mesothelioma patients than in healthy controls but were not significantly different to levels in patients with benign asbestos-related disease. CA15-3 in effusions could differentiate malignant from benign effusions but were not specific for mesothelioma. Thus, as in other cancers, alterations in MUC1 biology occur in mesothelioma and these results suggest that specific MUC1 characteristics may be useful for mesothelioma diagnosis and should also be investigated as a potential therapeutic target.}, } @article {pmid18449081, year = {2008}, author = {Pairon, JC and Andujar, P and Matrat, M and Ameille, J}, title = {[Occupational respiratory cancers].}, journal = {Revue des maladies respiratoires}, volume = {25}, number = {2}, pages = {193-207}, doi = {10.1016/s0761-8425(08)71517-1}, pmid = {18449081}, issn = {0761-8425}, mesh = {Humans ; Lung Neoplasms/diagnosis/*etiology ; Mesothelioma/diagnosis/etiology ; Occupational Diseases/diagnosis/*etiology ; Occupational Exposure/*adverse effects ; }, abstract = {Lung cancer and pleural mesothelioma are the most common occupational cancers. Recent epidemiological studies have estimated that the fraction attributable to occupational factors varies from 13 to 29% for lung cancer in men and is about 85% for pleural mesothelioma in men. Previous occupational exposure to asbestos is the most common occupational exposure in these cancers. Mesothelioma immediately leads the clinician to look for past asbestos exposure. In contrast, the search for an occupational exposure that should be routine in all cases of lung cancer, is generally more difficult because of the number of occupational aetiological factors and the absence of criteria that allow distinction of an occupational cancer from a tobacco related one. Therefore attention should be paid to the identification of occupational exposure in order to set up primary prevention programmes to prevent exposure still present in the working environment and, on the other hand, to identify the subjects entitled to the acknowledgement of occupational disease and/or to obtain the compensation available to asbestos victims.}, } @article {pmid18449002, year = {2008}, author = {Batirel, HF and Metintas, M and Caglar, HB and Yildizeli, B and Lacin, T and Bostanci, K and Akgul, AG and Evman, S and Yuksel, M}, title = {Trimodality treatment of malignant pleural mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {3}, number = {5}, pages = {499-504}, doi = {10.1097/JTO.0b013e31816fca1b}, pmid = {18449002}, issn = {1556-1380}, mesh = {Adult ; Aged ; Chemotherapy, Adjuvant ; Combined Modality Therapy ; Feasibility Studies ; Female ; Humans ; Lymphatic Metastasis ; Male ; Mesothelioma/mortality/pathology/*therapy ; Middle Aged ; Neoplasm Staging ; Pleural Neoplasms/mortality/pathology/*therapy ; Pneumonectomy ; Radiotherapy, Adjuvant ; Survival Analysis ; Treatment Outcome ; }, abstract = {INTRODUCTION: Multimodality treatment has achieved significant success in local control and treatment of early-stage malignant pleural mesothelioma patients. However, its favorable effect on survival is questionable.

METHODS: We have instituted a trimodality treatment protocol consisting of extrapleural pneumonectomy, adjuvant high-dose (54 Gy) hemithoracic irradiation, and platin-based chemotherapy in a multi-institutional setting. Preoperative pulmonary function tests, echocardiogram, chest computed tomography, and magnetic resonance imaging scans were performed in all patients. Twenty patients have been treated with this protocol during 2003-2007. Seventeen had a history of environmental asbestos/erionite exposure. Clinical stages were T1-3N0-2.

RESULTS: Median age was 56 (41-70, 8 female). There was one postoperative mortality (% 5) due to ARDS. Morbidity occurred in 11 patients (% 55). Histology was epithelial in 17, mixed in 2, and sarcomatoid in 1. Sixteen patients underwent extrapleural pneumonectomy. Microscopic margin positivity was present in 14 patients with macroscopic complete resection. Twelve patients completed all three treatments. Median follow-up was 16 months (1-43). Overall median survival was 17 months (24% at 2 years). Eight patients had extrapleural lymph node involvement (internal mammary [n = 3], subcarinal [n = 2], pulmonary ligament [n = 1], diaphragmatic [n = 1], subaortic [n = 1]). There was better survival in patients without lymph node metastasis (24 versus 13 months median survival, p = 0.052). Currently, 7 patients are alive, 6 without recurrence, and 2 patients at 40 and 45 months.

CONCLUSIONS: Trimodality treatment in malignant pleural mesothelioma seems to prolong survival in patients without lymph node metastasis. Novel techniques are needed for preoperative assessment of extrapleural lymph nodes.}, } @article {pmid18439258, year = {2008}, author = {Ahmed, I and Koulaouzidis, A and Iqbal, J and Tan, WC}, title = {Malignant peritoneal mesothelioma as a rare cause of ascites: a case report.}, journal = {Journal of medical case reports}, volume = {2}, number = {}, pages = {121}, pmid = {18439258}, issn = {1752-1947}, abstract = {INTRODUCTION: Peritoneal mesothelioma is a rare tumor with diagnostic and therapeutic problems. The peritoneum is the second most common site for development of mesothelioma, which in 30-45% of cases is associated with a synchronous pleural mesothelioma. Clinical symptoms and findings may be confusing and diagnosis can be easily overlooked especially in cases where there is no previous asbestos exposure.

CASE PRESENTATION: We report a case of malignant peritoneal mesothelioma in a 75-year-old woman who presented with ascites which, in the absence of inhalational exposure to asbestos, caused diagnostic confusion, and evaded radiological detection.

CONCLUSION: We concluded from this case that Peritoneal Mesothelioma although rare but should be considered among the differential diagnosis of Ascites.}, } @article {pmid18438715, year = {2008}, author = {Gasparrini, A and Pizzo, AM and Gorini, G and Seniori Costantini, A and Silvestri, S and Ciapini, C and Innocenti, A and Berry, G}, title = {Prediction of mesothelioma and lung cancer in a cohort of asbestos exposed workers.}, journal = {European journal of epidemiology}, volume = {23}, number = {8}, pages = {541-546}, pmid = {18438715}, issn = {0393-2990}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Cause of Death/*trends ; Cohort Studies ; Follow-Up Studies ; Forecasting ; Humans ; Italy/epidemiology ; Logistic Models ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; Middle Aged ; Occupational Diseases/mortality ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*mortality ; Railroads ; Registries ; Risk Assessment ; }, abstract = {BACKGROUND: Several papers have reported state-wide projections of mesothelioma deaths, but few have computed these predictions in selected exposed groups.

OBJECTIVE: To predict the future deaths attributable to asbestos in a cohort of railway rolling stock workers.

METHODS: The future mortality of the 1,146 living workers has been computed in term of individual probability of dying for three different risks: baseline mortality, lung cancer excess, mesothelioma mortality. Lung cancer mortality attributable to asbestos was calculated assuming the excess risk as stable or with a decrease after a period of time since first exposure. Mesothelioma mortality was based on cumulative exposure and time since first exposure, with the inclusion of a term for clearance of asbestos fibres from the lung.

RESULTS: The most likely range of the number of deaths attributable to asbestos in the period 2005-2050 was 15-30 for excess of lung cancer, and 23-35 for mesothelioma.

CONCLUSION: This study provides predictions of asbestos-related mortality even in a selected cohort of exposed subjects, using previous knowledge about exposure-response relationship. The inclusion of individual information in the projection model helps reduce misclassification and improves the results. The method could be extended in other selected cohorts.}, } @article {pmid18420450, year = {2008}, author = {Neri, M and Ugolini, D and Dianzani, I and Gemignani, F and Landi, S and Cesario, A and Magnani, C and Mutti, L and Puntoni, R and Bonassi, S}, title = {Genetic susceptibility to malignant pleural mesothelioma and other asbestos-associated diseases.}, journal = {Mutation research}, volume = {659}, number = {1-2}, pages = {126-136}, doi = {10.1016/j.mrrev.2008.02.002}, pmid = {18420450}, issn = {0027-5107}, mesh = {Asbestos/*toxicity ; DNA Repair ; Genetic Predisposition to Disease ; Glutathione Transferase/genetics ; Humans ; Lung Neoplasms/*etiology/genetics ; Mesothelioma/*etiology/genetics ; Oxidative Stress ; Pleural Neoplasms/etiology/genetics ; Polymorphism, Genetic ; }, abstract = {Exposure to asbestos fibers is a major risk factor for malignant pleural mesothelioma (MPM), lung cancer, and other non-neoplastic conditions, such as asbestosis and pleural plaques. However, in the last decade many studies have shown that polymorphism in the genes involved in xenobiotic and oxidative metabolism or in DNA repair processes may play an important role in the etiology and pathogenesis of these diseases. To evaluate the association between diseases linked to asbestos and genetic variability we performed a review of studies on this topic included in the PubMed database. One hundred fifty-nine citations were retrieved; 24 of them met the inclusion criteria and were evaluated in the review. The most commonly studied GSTM1 polymorphism showed for all asbestos-linked diseases an increased risk in association with the null genotype, possibly linked to its role in the conjugation of reactive oxygen species. Studies focused on GSTT1 null and SOD2 Ala16Val polymorphisms gave conflicting results, while promising results came from studies on alpha1-antitrypsin in asbestosis and MPO in lung cancer. Among genetic polymorphisms associated to the risk of MPM, the GSTM1 null genotype and two variant alleles of XRCC1 and XRCC3 showed increased risks in a subset of studies. Results for the NAT2 acetylator status, SOD2 polymorphism and EPHX activity were conflicting. Major limitations in the study design, including the small size of study groups, affected the reliability of these studies. Technical improvements such as the use of high-throughput techniques will help to identify molecular pathways regulated by candidate genes.}, } @article {pmid18414321, year = {2008}, author = {Hughes, N and Arber, A}, title = {The lived experience of patients with pleural mesothelioma.}, journal = {International journal of palliative nursing}, volume = {14}, number = {2}, pages = {66-71}, doi = {10.12968/ijpn.2008.14.2.28597}, pmid = {18414321}, issn = {1357-6321}, mesh = {Humans ; Mesothelioma/*psychology/therapy ; Palliative Care ; Pleural Neoplasms/*psychology/therapy ; }, abstract = {This paper reports on a research study of five patients diagnosed with mesothelioma. The study used a phenomenological approach to explore patients' lived experience using in-depth interviews. The findings identify that patients have many unmet psychosocial and emotional needs and that there was a lack of information provided to patients about specialist supportive and palliative care services. A number of the patients found specialist supportive care by chance rather than by referral. In addition, patients were involved in complex medico-legal matters in relation to asbestos exposure, and this was an additional burden for them and their spouse or carer. A feeling of social isolation was also reported and a number of patients would welcome the opportunity to meet with other people in the same situation as themselves. In conclusion, there is a lack of attention to the emotional needs of this group of patients, which means that supportive care resources are not being accessed in a timely and flexible manner.}, } @article {pmid18409885, year = {2007}, author = {Menegozzo, S and Izzo, F and Canfora, ML and Petronzio, MF and Santoro, M and Menegozzo, M}, title = {[Case studies on the malignant mesothelioma in Pellezzano (SA)].}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {29}, number = {3 Suppl}, pages = {644}, pmid = {18409885}, issn = {1592-7830}, mesh = {Aged ; Asbestos/adverse effects ; Environmental Exposure/adverse effects ; Female ; Humans ; Italy ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; }, abstract = {41 malignant mesothelioma cases were reported between January 2000 and April 2007 in the province of Salerno. The small town of Pellezzano, near Salerno, has more cases than any other urban centre in the province; five mesothelioma cases (three male and two female) in Pellezzano (population 9,171 in 1991) means a standardized incidence rate of 32.7 males and 21.8 females per 100.000 inhabitants. That's very alarming, considering that in Italy mesothelioma standardized incidence rate per 100.000 inhabitants is 2,98 for males and 0,98 for females. Campania Mesothelioma Register aims to investigate which kind of exposure caused this abnormal incidence rate. All five patients answered the questionnaire and a team of doctors performed an on-the-spot investigation. The studies verified the existence of two kind of asbestos exposure, professional (Cotton Manufacture, Construction, Foundry) and environmental (cement-asbestos pre-fabricated since 1980 earthquake), that have to be analyzed further.}, } @article {pmid18409884, year = {2007}, author = {Menegozzo, M and Izzo, F and Canfora, ML and Petronzio, MF and Menegozzo, S}, title = {[Activity of the Campania Register of Mesothelioma from July 2003 to October 2007].}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {29}, number = {3 Suppl}, pages = {642-644}, pmid = {18409884}, issn = {1592-7830}, mesh = {Asbestos/adverse effects ; Female ; Humans ; Italy ; Male ; Mesothelioma/*epidemiology/etiology ; *Registries ; Surveys and Questionnaires ; }, abstract = {Campania Mesothelioma Register was established in 2002; its purpose is to record every case of malignant mesothelioma that occurs in the registered population of Campania. Its aim is to identify new dangerous asbestos sources, by giving patients a questionnaire about their working and living habits. The questionnaire used is by National Mesothelioma Register (ReNaM). Analyzing carefully the answers to the questionnaire, it is possible to classify patients' exposure with a code given by ReNaM. By means of a recognition identification network, COR Campania identified 492 cases of malignant mesothelioma (pleura, pericardium, peritoneum and tunica vaginalis of the testis) diagnosed between 1996-2007. The analysis of the ReNaM questionnaire confirms a prevalence of professional exposures (71%), however unknown exposures (15%) also play an important role. The economic sector that determined the greatest number of professional exposures are Construction (17.5%), Industrial Metalwork (13.13%), Railway Car (9.3%), Vehicle production and maintenance (8.16%), Ship building (7.5%).}, } @article {pmid18409883, year = {2007}, author = {Todaro, A and Bordini, L and Rubagotti, M and Mensi, C and Riboldi, L}, title = {[Health surveillance in workers with a previous exposure to asbestos: a method of retrospective evaluation of exposition].}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {29}, number = {3 Suppl}, pages = {641-642}, pmid = {18409883}, issn = {1592-7830}, mesh = {Asbestos/*adverse effects ; Humans ; Male ; Middle Aged ; Occupational Exposure/*adverse effects ; Population Surveillance/methods ; Retrospective Studies ; }, abstract = {The medical surveillance of the previously exposed to asbestos like method of retrospective appraisal of the exposure. The medical surveillance of the previously exposed to asbestos is effected on indication of the Competent Physician by the DL 257/2006. An aspect that often countersigns such typology of surveillance is the lack of relative data about past environmental asbestos exposure. There've been submitted to sanitary controls 140 subject employees in a steel metal company where in past activity of heavy carpentry has been developed. All the subjects have been submitted in the period 1998-2007 to medical visit, PFR with DLCO, radiography of the chest, in some cases TC and BAL. The past exposure has been resulted inclusive between 1962 and 1981. None of these workers has developed asbestosis, while the 10% of the subjects have showed bilateral pleural plaques. 12 subjects have been submitted to close examination through BAL for the determination of the internal dose of asbestos with comparison of middle values of 3.9 ca /ml. Four cases of pulmonary neoplasm and any case of mesothelioma have been diagnosed. This experience shows as the medical surveillance of a homogeneous group of workers can furnish useful data also to frame previous asbestos exposure in absence of environmental data.}, } @article {pmid18409882, year = {2007}, author = {Luisi, V and Marinaccio, A and Mera, ES and Dario, R and Licchelli, B and Molinini, R}, title = {[Pleural mesothelioma in barman with probable occupational exposure to asbestos].}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {29}, number = {3 Suppl}, pages = {640-641}, pmid = {18409882}, issn = {1592-7830}, mesh = {Asbestos/*adverse effects ; Humans ; Male ; Mesothelioma/diagnosis/*etiology ; Middle Aged ; Occupational Diseases/diagnosis/*etiology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/diagnosis/*etiology ; }, abstract = {The case of a barman who suffer from Malignant Mesothelioma (MM) has been signaled. For this case it has been documented a possible source of occupational exposure to asbestos caused by the presence of asbestos components in the professional espressos coffee machines. In some gaskets which are part of these coffee machines, we verified the presence of chrysotile fibers. Italian National Mesothelioma Register have reported a MM case with a professional origin arised in a barman with a certain diagnosis in 1999 (Tuscany Region).}, } @article {pmid18409881, year = {2007}, author = {Venuti, V and De Pasquale, D and Abbate, A and Brecciaroli, R and Giorgianni, C}, title = {[Malignant pleuric mesothelioma in Sicily. Epidemiologic observations during the time 1998-2005].}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {29}, number = {3 Suppl}, pages = {639-640}, pmid = {18409881}, issn = {1592-7830}, mesh = {Asbestos/*adverse effects ; Female ; Humans ; Incidence ; Italy ; Male ; Mesothelioma/*epidemiology ; Pleural Neoplasms/*epidemiology ; }, abstract = {Pleural malign mesothelioma is the only one to which we can straight attribute to an exposition, in professional and ambient ambit, to a good identified agent and, precisely, to the fibres of asbestos. Objective of our work has been to verify the incidence of the pleural malign mesothelioma in Sicily and in particular in the Messina's area, during the period 1988-2005. We have examined the epidemiologic data of the period 1988-1997 and 1998-2005 through the consultation of the Mesothelioma Sicilian Register; Mesothelioma Italian Register and of the available documentation in the Health Superior Institute. The study showed that the pleural malign mesothelioma in sicily and in Messina's area is reduced for the elimination of the asbestos and for the low use of asbestos in the sicilian industry.}, } @article {pmid18409858, year = {2007}, author = {Ballarin, MN and Alessandrì, MV and Marchì, T and Montagnani, R and Virgili, A and Magarotto, G}, title = {[Epidemiology of work-related diseases in ULSS 12 Venice (Italy)].}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {29}, number = {3 Suppl}, pages = {604-605}, pmid = {18409858}, issn = {1592-7830}, mesh = {Humans ; Italy ; Occupational Diseases/*epidemiology ; }, abstract = {In Veneto, like in Italy, in the last years the course of the professional diseases shown a trend in reduction. This trend has had to the difficulty to recognize the professional aetiology of multifactorial diseases. In the Venice the analysis of the course of the professional diseases in last the 4-5 years has demonstrated an increase of the communications of diseases from the doctors who operate in hospital to the SPISAL for the active search for pathologies asbestos and CVM correlated; moreover it has been a reduction of the hearing loss from noise from 2000 and it has been increment of cancer of lung and mesothelioma from 2001. Emergent diseases, like the allergy, the back diseases and those tied to the organizational constriction, are sottostimate. They have been a collaboration with the doctors of hospital, the doctors of factories, the INAIL and the court.}, } @article {pmid18409719, year = {2007}, author = {Somenzi, V and Lattarini, M}, title = {[Exposure to asbestos dust in agricultural environment. Some significant exposure forms documented by the Hospital Unit of Occupational Medicine of Hospital Institute of Cremona].}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {29}, number = {3 Suppl}, pages = {349-350}, pmid = {18409719}, issn = {1592-7830}, mesh = {Aged ; *Agriculture ; Asbestos/*adverse effects ; *Dust ; Hospitals ; Humans ; Italy ; Male ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; Occupational Exposure/*adverse effects ; Occupational Medicine ; Pleural Neoplasms/*etiology ; }, abstract = {Although it is difficult to document the exposition to asbestos in the agricultural workers, mesotelioma has however been noticed in the rural environment that may seem to have low risk because of its nature. This work describes the systematic diffusion of asbestos dust in the rural environment near Cremona due to the activity of "non-agricultural" workers who have fallen ill with mesothelioma. The patient described their work in details to the occupational medical doctor underlining the circumstances and the ways asbestos dust has been diffused in the rural environment. These ways were carefully analysed by the occupational medical doctor. They explain the onset of the mesothelioma in patients and they prove a systematic and long contamination of the involved rural areas. The described diffusion of dust has probably provoked a noteworthy exposure to the agricultural workers. At the moment there aren't full-blown asbestos-linked pathology but these workers are potentially at risk of getting them. So it has an importance both on individual and global level for the rural area near Cremona.}, } @article {pmid18409718, year = {2007}, author = {Adesi, FB and Ferrante, D and Bertolotti, M and Todesco, A and Mirabelli, D and Terracini, B and Magnani, C}, title = {[Mortality from pleural and peritoneal cancer in a cohort of asbestos workers, many years after start of the exposure: possible role of fibers clearance].}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {29}, number = {3 Suppl}, pages = {346-348}, pmid = {18409718}, issn = {1592-7830}, mesh = {Asbestos/*adverse effects ; Female ; Humans ; Male ; Mineral Fibers/*adverse effects ; Occupational Diseases/epidemiology/*etiology/*mortality ; Occupational Exposure/*adverse effects ; Peritoneal Neoplasms/epidemiology/*etiology/*mortality ; Pleural Neoplasms/epidemiology/*etiology/*mortality ; Time Factors ; }, abstract = {The multistage theory of carcinogenesis assumes rates of mesothelioma increasing monotonically as a function of time since first exposure (TSFE) to asbestos. However, some authors have suggested that the increase in mesothelioma rate with TSFE might be attenuated by clearance of asbestos from the lungs. We estimated mortality time trends from pleural and peritoneal cancer in a cohort of 3443 asbestos-cement workers. The role of asbestos clearance was explored using the traditional mesothelioma multistage model, generalized to include a term representing elimination over time. We observed 139 deaths from pleural and 56 from peritoneal cancer during the period 1950-2003. The rate of pleural cancer increased during the first 40 years of TSFE and reached a plateau thereafter. In contrast, the rate of peritoneal cancer increased monotonically with TSFE. The model allowing for asbestos elimination fitted the data better than the traditional model for pleural (p = 0.02) but not for peritoneal cancer (p = 0.22). The risk for pleural cancer, rather than showing an indefinite increase, might reach a plateau when a sufficiently long time has elapsed since exposure. The different trends for pleural and peritoneal cancer might be related to clearance of the asbestos from the workers' lungs.}, } @article {pmid18409716, year = {2007}, author = {Foddis, R and Vivaldi, A and Filiberti, R and Puntoni, R and Mutti, L and Ambrosino, N and Chella, A and Guglielmi, G and Gattini, V and Buselli, R and Perretta, S and Cristaudo, A}, title = {[Serum mesothelin dosages in follow-up of previously exposed workers].}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {29}, number = {3 Suppl}, pages = {342-345}, pmid = {18409716}, issn = {1592-7830}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Female ; Follow-Up Studies ; GPI-Linked Proteins ; Humans ; Male ; Membrane Glycoproteins/*blood ; Mesothelin ; Mesothelioma/blood/diagnosis/etiology ; Middle Aged ; Occupational Exposure/*analysis ; Prospective Studies ; }, abstract = {High dosages of Serum Mesothelin have been demonstrated to be significantly associated to Pleural Malignant Mesothelioma. We recently demonstrated that Serum Mesothelin may be clinically helpful both for diagnostic and prognostic purposes, with the best cut-off corresponding to 1 nM. We also discovered that high levels of Serum Mesothelin are significantly associated to Lung Cancer. The usefulness of this marker in secondary prevention has been suggested, though never demonstrated. We therefore started a long-term prospective cohort study including previously asbestos-exposed workers. These subjects periodically underwent both radiological tests and serum mesothelin dosages. As a mid-term goal of this longitudinal study we decided to check the variability of mesothelin dosages, comparing baseline and follow-up values, as well as the possible correlation with age, duration of exposure, smoking, any abnormality of respiratory functional tests (RFT) and/or radiological tests. At baseline, Mesothelin mean value was 0.66 +/- 0.4 (range 0.08-2.2 nM). Both age (p = 0.04) and abnormal thoracic TC (p = 0.04) were significantly correlated with increased serum mesothelin levels and increasing age. No association was found between baseline mesothelin levels and duration of asbestos exposure (p = 0.5), smoking habits (p = 0.2), abnormal RFT, DLCO (carbon monoxide diffusing capacity) or thoracic X-ray. No significant variation was observed between mesothelin values at baseline and at follow-up (p = 0.2).}, } @article {pmid18409714, year = {2007}, author = {Luisi, V and Dario, R and Serio, G and Licchelli, B and Mera, ES and Molinini, R}, title = {[Asbestos-related diseases in relatives of asbestos exposed workers].}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {29}, number = {3 Suppl}, pages = {338-339}, pmid = {18409714}, issn = {1592-7830}, mesh = {Adult ; Aged ; Asbestosis/*epidemiology ; Environmental Exposure/*adverse effects ; *Family Health ; Female ; Humans ; Male ; Occupational Exposure/*adverse effects ; }, abstract = {Standard asbestos diagnostic protocol was applied to eleven relatives of asbestos exposure ex-workers of a cement factory in Bari. Nine wives and seventeen sons were involved as volunteers in this evaluation. In this group two pleura malignant mesotheliomas (not dose-dependent) two asbestosis and fifteen pleura plaques (dose-dependent) were detected. This situation shows high level of asbestos contamination at home. For all the test patients the contamination most probably occurred because workers carried asbestos substances home from work on their clothes.}, } @article {pmid18409713, year = {2007}, author = {Amati, M and Tomasetti, M and Scartozzi, M and Mariotti, L and Ciuccarelli, M and Valentino, M and Governa, M and Santarelli, L}, title = {[Biomarkers for prevention and early diagnosis of malignant pleural mesothelioma].}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {29}, number = {3 Suppl}, pages = {335-338}, pmid = {18409713}, issn = {1592-7830}, mesh = {Biomarkers, Tumor/analysis/*blood ; Early Diagnosis ; Female ; Humans ; Lymphocytes ; Male ; Mesothelioma/blood/*diagnosis/*prevention & control ; Middle Aged ; Pleural Neoplasms/blood/diagnosis/*prevention & control ; }, abstract = {Improved detection methods for diagnosis of asymptomatic malignant pleural mesothelioma (MPM) are essential for an early and reliable detection and treatment of this disease. Thus, focus has been on finding tumour markers in the blood. 94 asbestos-exposed subjects, 22 patients with MM, and 54 healthy subjects were recruited for evaluation of the significance of 8-hydroxy-2'-deoxy-guanosine (80HdG) in white blood cells and plasma concentrations of soluble mesothelin-related peptides (SMRPs), angiogenic factors (PDGFbeta, HGF, bFGF, VEGFbeta), and matrix proteases (MMP2, MMP9, TIMP1, TIMP2) for potential early detection of MM. The area under ROC curves (AUC) indicates that 80HdG levels can discriminate asbestos-exposed subjects from controls but not from MPM patients. Significant AUC values were found for SMRP discriminating asbestos-exposed subjects from MPM patients but not from controls. VEGFbeta can significantly differentiate asbestos-exposed subjects from control and cancer groups. No diagnostic value was observed for MMP2, MMP9, TIMP1, TIMP2. The sensitivity and specificity results of markers were calculated at defined cut-offs. The combination of 80HdG, VEGFbeta and SMRPs best distinguished the individual groups, suggesting a potential indicator of early and advanced MPM cancers. The combination of blood biomarkers and radiographic findings could be used to stratify the risk of mesothelioma in asbestos-exposed populations.}, } @article {pmid18409712, year = {2007}, author = {De Zotti, R and Damian, A and Muran, A}, title = {[Malignant mesothelioma (MM) in women: findings of the Mesothelioma Register of the Friuli Venezia Giulia Region].}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {29}, number = {3 Suppl}, pages = {334-335}, pmid = {18409712}, issn = {1592-7830}, mesh = {Aged ; Female ; Humans ; Male ; Mesothelioma/*epidemiology/etiology ; Pleural Neoplasms/*epidemiology/etiology ; Sex Factors ; }, abstract = {During the period 2000-2003, the Mesothelioma Register of the Friuli Venezia Giulia identified 248 cases of MM, 44 of which (18%) were female. In 36 cases the diagnosis was "certain" and in 8 "probable" or "possible". Mean age at diagnosis was 72.8 years (SD = 12.7), and the site of the disease was the pleura in 93% of cases. Information about previous exposure to asbestos was collected in accordance with the guidelines of the National Mesothelioma Register Occupational exposure to asbestos was documented in only 8 cases and family exposure in 6 others. In the remaining cases the source of exposure was "unknown" because of insufficient data, or there were no data at all. The study highlights the role played by extra-occupational exposure to asbestos among women and the need for careful investigation into previous asbestos exposure in all females with MM. In order to improve our knowledge of the part played by factors other than occupational exposure to asbestos in triggering the disease, it is crucial to reduce he number of cases with no information or "unknown" exposure to this dangerous substance.}, } @article {pmid18409711, year = {2007}, author = {Montomoli, L and Spisso, M and Romeo, R and Spina, D and Ghiribelli, C and Sartorelli, P}, title = {[Work related mesothelioma: analysis of cases discovered at the Section for Occupational Medicine and Toxicology of Siena University during the years 2000-2007].}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {29}, number = {3 Suppl}, pages = {332-333}, pmid = {18409711}, issn = {1592-7830}, mesh = {Aged ; Asbestos/adverse effects ; Female ; Humans ; Italy ; Male ; Mesothelioma/*epidemiology/etiology ; Occupational Diseases/*epidemiology/etiology ; Pleural Neoplasms/*epidemiology/etiology ; Universities ; }, abstract = {This study focuses on the spread of mesothelioma in Siena. The population consisted of 30 patients. The diagnosis was made through histopathological and immunoistochemical or cytological and immunoistochemical analysis. The association between malignant masothelioma and exposure to asbestos was deduced by the occupational history. The mesothelioma was noted both in traditional industries and other jobs such as the chain of manifacture, plumbers, electricians, carpenters, installers of asbestos insulation and construction workers. Thus it is possible to find other malignant and nonmalignant asbestos-related diseases more frequently than mesothelioma. There is an evident risk in rebuilding, so the development of new cases due to these exposures is expected.}, } @article {pmid18408949, year = {2009}, author = {Moshammer, H and Neuberger, M}, title = {Lung function predicts survival in a cohort of asbestos cement workers.}, journal = {International archives of occupational and environmental health}, volume = {82}, number = {2}, pages = {199-207}, pmid = {18408949}, issn = {1432-1246}, mesh = {Asbestos/*adverse effects ; Asbestosis/diagnosis/mortality/*physiopathology ; Austria/epidemiology ; Cohort Studies ; *Construction Materials ; Industry ; *Life Expectancy ; Lung/diagnostic imaging/*drug effects/physiopathology ; Mass Screening ; Occupational Exposure/*adverse effects ; Predictive Value of Tests ; Radiography ; Respiratory Function Tests ; Survival Rate ; }, abstract = {PURPOSE: To study the predictive power of respiratory screening examinations a cohort of asbestos workers was followed from active work in an asbestos cement plant until death.

METHODS: From a cohort with data on individual exposure since first employment 309 workers who had a preventive medical examination in 1989/1990 were observed until death or the end of 2006. The impact of asbestos exposure (fibre years) and of smoking history on lung function was examined by linear regression, on specific causes of death and total mortality by Cox regression. The prognostic value of lung function, chest X-ray, and various clinical findings regarding total mortality was also examined by Cox regression.

RESULTS: Lung function proved to be the best predictor of survival apart from current smoking. Depending on the lung function variable an impairment by the interquartile range resulted in a hazard ratio of 1.5-1.6 while for current smokers it was 2.3. An increase of 70 fibre years (interquartile range) led to a hazard ratio of only 1.1. Lung function was influenced by asbestos exposure, current (but not former) smoking, and by pathological X-ray findings. The risk for pleural mesothelioma was dominated by time since first exposure to crocydolite in the pipe factory while the risk for bronchial cancer increased with smoking and total fibre years. An unexpected finding was an increase of gastric cancer in asbestos cement workers.

CONCLUSION: Lung function decrease predicts risk of premature death better than exposure history and regular spirometry should therefore be offered as primary screening to all former asbestos workers. In workers with a history of high cumulative exposure or rapid lung function decrease or radiological signs (diffuse pleural thickening or small irregular opacities) more sensitive techniques (high resolution computer tomography) need to be applied. All smokers with a history of asbestos exposure should be given free smoking cessation therapy to prevent premature death and lung cancer in particular.}, } @article {pmid18408444, year = {2008}, author = {Takeuchi, N and Nakai, M and Sato, M}, title = {[A case of omental mesothelioma presenting with laminar thickening of omentum-appearances of diffuse malignant peritoneal mesothelioma].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {35}, number = {4}, pages = {677-681}, pmid = {18408444}, issn = {0385-0684}, mesh = {Aged ; Diffusion ; Humans ; Magnetic Resonance Imaging ; Male ; Mesothelioma/*diagnostic imaging/drug therapy/*pathology ; Middle Aged ; Omentum/*diagnostic imaging/drug effects/*pathology ; Radionuclide Imaging ; Tomography, X-Ray Computed ; Treatment Failure ; }, abstract = {A man in his 60's with no apparent history of asbestos exposure was admitted to our hospital with a chief complaint of abdominal fullness. CA125 levels in serum and ascites were veryhigh. Enhanced abdominal CT confirmed a large amount of ascites, inflexible intestinal canal, short mesentery and laminar thickening of the omentum. SPIO-enhanced MRI-T1WI slightly enhanced the thickened omentum. These T1WI images largely matched portal-phase contrast CT images. Furthermore, the thickened omentum was clearly visualized by lowering the signal for the liver and spleen by SPIO and by suppressing the ascites signal by fluid-attenuated inversion recovery (FLAIR). Gascintigraphy confirmed Ga accumulation in the same areas. Chemotherapy was ineffective, and the patient died of liver metastasis in February 2006. Autopsy confirmed biphasic malignant peritoneal mesothelioma. The involvement of asbestos is clear in the onset of malignant peritoneal mesothelioma. Therefore, it is possible that the patient unintentionally inhaled asbestos. Hence, when levels of CA125 in serum and/or ascites are high, it is important to differentiate malignant peritoneal mesothelioma from primaryserous papillary carcinoma of the peritoneum. Here, we experienced a case of biphasic diffused omental mesothelioma. While studies have documented laminar thickening of the omentum by abdominal incision, this is thought to be first case in Japan in which laminar thickening of the omentum was detected on diagnostic imaging. Laminar thickening of the omentum and short mesentery are thought to be characteristic features of diffused peritoneal mesothelioma when subjective symptoms appear. In addition, Gascintigraphy and FDG-PET are useful auxiliary diagnostic tools. In the future, we hope to differentiate epithelial, sarcomatous and biphasic types based on imaging findings.}, } @article {pmid18407510, year = {2008}, author = {Aigner, C and Hoda, MA and Lang, G and Taghavi, S and Marta, G and Klepetko, W}, title = {Outcome after extrapleural pneumonectomy for malignant pleural mesothelioma.}, journal = {European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery}, volume = {34}, number = {1}, pages = {204-207}, doi = {10.1016/j.ejcts.2008.03.003}, pmid = {18407510}, issn = {1010-7940}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Combined Modality Therapy ; Epidemiologic Methods ; Female ; Humans ; Male ; Mesothelioma/pathology/*surgery/therapy ; Middle Aged ; Neoplasm Staging ; Pleural Neoplasms/pathology/*surgery/therapy ; Pneumonectomy/*methods ; Treatment Outcome ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma is a mainly asbestos-related neoplasm that occurs with increasing frequency and is associated with a poor prognosis. Extrapleural pneumonectomy which was initially performed as a stand-alone treatment in patients with resectable disease is now currently almost uniformly applied as part of a multi-modal approach. Its value and advantage over other therapeutic strategies remain points of discussion. We therefore analysed our experience with extrapleural pneumonectomy in the treatment of malignant pleural mesothelioma.

METHODS: We retrospectively reviewed our institutional experience with all consecutive patients undergoing extrapleural pneumonectomy for malignant pleural mesothelioma from 1994 to 2005. Patients were analysed with regard to hospital mortality and morbidity and long-term outcome.

RESULTS: Forty-nine patients (10 female/39 male, mean age 58+12 years) underwent extrapleural pneumonectomy during the observation period. Median ICU stay was 1 day, median postoperative length of hospital stay was 13 days. After a mean follow-up of 2573 days, median survival was 376 days (mean 672+121 days, range 9-3384). One-year survival was 53%, 3-year survival 27% and 5-year survival 19%.

CONCLUSION: Extrapleural pneumonectomy as part of a multi-modality treatment regimen is a good treatment option for selected patients with malignant pleural mesothelioma. The long-term results of this limited series compare favourably to non-surgical treatment regimens. Larger randomised prospective multi-centre trials are warranted to establish clear guidelines.}, } @article {pmid18396365, year = {2008}, author = {Gamble, JF and Gibbs, GW}, title = {An evaluation of the risks of lung cancer and mesothelioma from exposure to amphibole cleavage fragments.}, journal = {Regulatory toxicology and pharmacology : RTP}, volume = {52}, number = {1 Suppl}, pages = {S154-86}, doi = {10.1016/j.yrtph.2007.09.020}, pmid = {18396365}, issn = {1096-0295}, mesh = {Air Pollutants, Occupational/*adverse effects/classification ; Asbestos, Amphibole/*adverse effects/classification ; Asbestosis/epidemiology/*etiology ; Carcinogens, Environmental/*adverse effects ; Humans ; Lung Neoplasms/epidemiology/*etiology ; Male ; Mesothelioma/epidemiology/*etiology ; Mineral Fibers/adverse effects ; Odds Ratio ; Particle Size ; Particulate Matter/analysis/chemistry ; Risk Assessment ; }, abstract = {Amphiboles are hydrated mineral silicates five of which occur in asbestiform habits as asbestos grunerite (amosite) asbestos, riebeckite (crocidolite) asbestos, anthophyllite asbestos, tremolite asbestos and actinolite asbestos] and non-asbestiform habits (grunerite, riebeckite, anthophyllite, tremolite and actinolite). The asbestiform varieties are characterized by long, thin fibers while non-asbestiform varieties such as cleavage fragments form short fibers with larger widths. The U.S. regulatory method for counting asbestos fibers (aspect ratio > or = 3:1, length > or = 5 microm) does not distinguish between asbestos and cleavage fragments. The method biases toward increased counts of non-asbestiform cleavage fragments compared to long, thin asbestos fibers. One consequence of this regulatory approach is that workers can be erroneously classified as exposed to concentrations of asbestos (asbestiform amphiboles) above the U.S. 0.1 f/mL exposure standard when in fact they are not exposed to asbestos at all but non-asbestiform amphibole cleavage fragments. Another consequence is that the known carcinogenic effects of asbestos may be falsely attributed to non-asbestiform amphibole cleavage fragments of the same mineral. The purpose of this review is to assess whether amphibole cleavage fragments pose the same risk of lung cancer and mesothelioma characteristic of amphibole asbestos fibers. We identified three groups of workers exposed to non-asbestiform amphiboles: two groups exposed to grunerite (Homestake gold miners and taconite miners) and one group exposed to industrial talc containing non-asbestiform tremolite and anthophyllite in St. Lawrence County, NY. In addition to assessing strength of association and exposure-response trends in the non-asbestiform amphibole cohorts, comparisons were also made with cohorts exposed to the asbestiform counterpart (positive control) and cohorts exposed to the mineral (e.g. talc) that does not contain amphiboles (negative controls). The cohorts exposed to non-asbestiform amphiboles had no excesses of lung cancer or mesothelioma. Similar results were observed in the negative control groups, in stark contrast to the excess risks of asbestos-related disease found in the asbestos cohorts. The only possible exception is the twofold increased risk of lung cancer where exposure was to industrial talc containing cleavage fragments of tremolite and anthophyllite. However, this risk is not considered attributable to the talc or amphibole cleavage fragments for several reasons. A similar increased risk of lung cancer was found in Vermont talc workers, studied in the same time period. Their exposure was to relatively pure talc. There was no relationship between lung cancer mortality and exposure measured as mg/m(3)years and years worked. A case-control study reported that all the lung cancer cases were smokers (or former smokers) and attributed the excess to smoking. There were two mesothelioma cases among the NY State talc workers exposed to cleavage fragments of tremolite and anthophyllite, but talc is not a plausible cause because of too short latency and potential for previous asbestos exposure. The positive controls of tremolite asbestos and anthophyllite asbestos exposed workers showed excess risks of both lung cancer and mesothelioma and positive exposure-response trends. St. Lawrence, NY talc does not produce mesotheliomas in animals while amphibole asbestos does. In sum, the weight of evidence fully supports a conclusion that non-asbestiform amphiboles do not increase the risk of lung cancer or mesothelioma.}, } @article {pmid18394767, year = {2008}, author = {Gibbs, GW}, title = {Rapporteur's Report Session 3: exposure to grunerite (amosite) asbestos: historical perspectives of the health effects.}, journal = {Regulatory toxicology and pharmacology : RTP}, volume = {52}, number = {1 Suppl}, pages = {S91}, doi = {10.1016/j.yrtph.2008.02.004}, pmid = {18394767}, issn = {1096-0295}, mesh = {Air Pollutants, Occupational/adverse effects ; Asbestos, Amosite/*adverse effects ; Asbestosis/epidemiology/*etiology ; Environmental Exposure/*adverse effects ; Humans ; Mesothelioma/*chemically induced/etiology/mortality ; Mineral Fibers/adverse effects ; *Mining ; New Jersey/epidemiology ; South Africa/epidemiology ; Texas/epidemiology ; United Kingdom/epidemiology ; }, } @article {pmid18394747, year = {2008}, author = {Iwahori, K and Osaki, T and Serada, S and Fujimoto, M and Suzuki, H and Kishi, Y and Yokoyama, A and Hamada, H and Fujii, Y and Yamaguchi, K and Hirashima, T and Matsui, K and Tachibana, I and Nakamura, Y and Kawase, I and Naka, T}, title = {Megakaryocyte potentiating factor as a tumor marker of malignant pleural mesothelioma: evaluation in comparison with mesothelin.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {62}, number = {1}, pages = {45-54}, doi = {10.1016/j.lungcan.2008.02.012}, pmid = {18394747}, issn = {0169-5002}, mesh = {Adult ; Area Under Curve ; Biomarkers, Tumor/*blood ; Blotting, Western ; Enzyme-Linked Immunosorbent Assay/*methods ; Flow Cytometry ; GPI-Linked Proteins ; Humans ; Immunoprecipitation ; Membrane Glycoproteins/*blood ; Mesothelin ; Mesothelioma/*blood ; Pleural Neoplasms/*blood ; Protein Isoforms/blood ; ROC Curve ; Sensitivity and Specificity ; }, abstract = {PURPOSE: An early and reliable blood test is one deficiency in diagnosis of malignant pleural mesothelioma (MPM). Megakaryocyte potentiating factor (MPF) and mesothelin variants (MSLN), members of the mesothelin gene family, have been studied as candidate serum markers for MPM. We developed a novel enzyme-linked immunosorbent assay (ELISA) system to compare the diagnostic efficacy of MPF and MSLN in MPM and control groups.

EXPERIMENTAL DESIGN: MPF and MSLN were assayed with ELISA in 27 consecutive MPM patients and 129 controls including patients with lung cancer and asymptomatic asbestos-exposed subjects.

RESULTS: Statistically significant elevation of serum MPF and MSLN levels was noted in MPM patients in comparison with every control group. The area under the receiver operating characteristic curve (AUC) was calculated for differentiation of MPM and lung cancer, healthy asbestos-exposed subjects, and healthy adults. While the AUC for serum MPF was 0.879, cut-off=19.1ng/ml (sensitivity=74.1%, specificity=90.4%), the AUC for serum MSLN was 0.713, cut-off=93.5ng/ml (sensitivity=59.3%, specificity=86.2%). Comparison between AUC for MPF and MSLN values shows that MPF is significantly superior to MSLN (p=0.025). Finally, there was a significant correlation between MPF and MSLN values for MPM (Pearson's correlation coefficient=0.77; p<0.001).

CONCLUSIONS: These findings suggest that diagnostic value of MPF for MPM was better than that of MSLN although both markers showed almost equal specificity for MPM.}, } @article {pmid18385176, year = {2008}, author = {Riganti, C and Doublier, S and Aldieri, E and Orecchia, S and Betta, PG and Gazzano, E and Ghigo, D and Bosia, A}, title = {Asbestos induces doxorubicin resistance in MM98 mesothelioma cells via HIF-1alpha.}, journal = {The European respiratory journal}, volume = {32}, number = {2}, pages = {443-451}, doi = {10.1183/09031936.00090407}, pmid = {18385176}, issn = {1399-3003}, mesh = {ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism ; Antineoplastic Agents/pharmacology ; Asbestos/*toxicity ; Asbestos, Crocidolite/pharmacology ; Cell Line, Tumor ; Doxorubicin/pharmacology ; *Drug Resistance, Neoplasm ; Humans ; Hypoxia ; Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism ; Iron/metabolism ; Lung/pathology ; Lung Neoplasms/*drug therapy ; Mesothelioma/*drug therapy ; Razoxane/pharmacology ; }, abstract = {Human malignant mesothelioma (HMM), which is strongly related to asbestos exposure, exhibits high resistance to many anticancer drugs. Asbestos fibre deposition in the lung may cause hypoxia and iron chelation at the fibre surface. Hypoxia-inducible factor (HIF)-1alpha, which is upregulated by a decreased availability of oxygen and iron, controls the expression of membrane transporters, such as P-glycoprotein (Pgp), which actively extrude the anticancer drugs. The present study aimed to assess whether asbestos may play a role in the induction of doxorubicin resistance in HMM cells through the activation of HIF-1alpha and an increased expression of Pgp. After 24-h incubation with crocidolite asbestos or with the iron chelator dexrazoxane, or under hypoxia, HMM cells were tested for HIF-1alpha activation, Pgp expression, accumulation of doxorubicin and sensitivity to its toxic effect. Crocidolite, dexrazoxane and hypoxia caused HIF-1alpha activation, Pgp overexpression and increased resistance to doxorubicin accumulation and toxicity. These effects were prevented by the co-incubation with the cell-permeating iron salt ferric nitrilotriacetate, which caused an increase of intracellular iron bioavailability, measured as increased activity of the iron regulatory protein-1. Crocidolite, dexrazoxane and hypoxia induce doxorubicin resistance in human malignant mesothelioma cells by increasing hypoxia-inducible factor-1alpha activity, through an iron-sensitive mechanism.}, } @article {pmid18381361, year = {2008}, author = {Beshay, M and Carboni, G and Hoksch, B and Reymond, MA and Schmid, RA}, title = {The role of muscle flap in preventing bronchus stump insufficiency after pneumonectomy for malignant pleural mesothelioma in high-risk patients.}, journal = {Interactive cardiovascular and thoracic surgery}, volume = {7}, number = {4}, pages = {621-4; discussion 624-5}, doi = {10.1510/icvts.2007.166546}, pmid = {18381361}, issn = {1569-9285}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Bronchial Diseases/etiology/*prevention & control ; Chemotherapy, Adjuvant ; Female ; Humans ; Male ; Mesothelioma/mortality/*surgery ; Middle Aged ; Muscle, Skeletal/*transplantation ; Neoadjuvant Therapy ; Pleural Neoplasms/mortality/*surgery ; Pneumonectomy/*adverse effects ; Radiotherapy, Adjuvant ; Retrospective Studies ; *Surgical Flaps ; Thoracotomy ; Treatment Outcome ; }, abstract = {Bronchus stump insufficiency (BSI) is one of the major complications after pneumonectomy; we analyzed all patients who underwent extra pleural pneumonectomy (EPP) for malignant pleural mesothelioma (MPM) in order to detect the role of muscle flap (MF) on preventing early and late stump insufficiency. From January 2000 until December 2005, there were 42 patients admitted with MPM for further intervention at our institution. Thirty patients were suitable for surgery and thus received a multimodal treatment with neo-adjuvant chemotherapy using Cisplatin and Gemcitabin (Gemzar), EPP followed by 54 Gray (Gy) adjuvant radiotherapy. Data were collected from the surgical and oncological records. There were 37 male patients (88%), the median age was 65 years (range 40-83 years). Seven (17%) patients had concomitant diseases. Forty patients (95%) had asbestos exposition. The operative procedures were EPP with muscle flap through an anterolateral thoracotomy. Univariate and multivariate analyses were done. One patient (3%) died on the 2nd postoperative day due to lung embolism. Mild complications were noticed in the early postoperative phase in 8 (25%) patients. There was no early or late stump insufficiency during the 15-month follow-up. Surgical techniques using muscle flap seems to play a major role in the prevention of bronchus stump insufficiency especially after neo-adjuvant chemotherapy.}, } @article {pmid18350972, year = {2007}, author = {Forsell, K and Hageberg, S and Nilsson, R}, title = {Lung cancer and mesothelioma among engine room crew--case reports with risk assessment of previous and ongoing exposure to carcinogens.}, journal = {International maritime health}, volume = {58}, number = {1-4}, pages = {5-13}, pmid = {18350972}, issn = {1641-9251}, mesh = {Adolescent ; Adult ; Air Pollutants, Occupational/*analysis ; Asbestos/toxicity ; Carcinogens/*toxicity ; Humans ; Lung Neoplasms/*chemically induced ; Male ; Men's Health ; Mesothelioma/*chemically induced ; Middle Aged ; Occupational Diseases/*chemically induced ; Occupational Exposure ; Polycyclic Aromatic Hydrocarbons/toxicity ; Risk Assessment/*methods ; Risk Factors ; *Ships ; Sweden ; }, abstract = {OBJECTIVE: The aim of this article is to illustrate, by means of case reports on occupational exposure in four men with cancer, the hazards of previous and ongoing carcinogenic exposures in ships' engine rooms. Several cases of cancer occurred within a few years among the engine room crew of a passenger ferry. An investigation was undertaken to establish the number of cases, the types of cancers involved, and their possible relation to work.

SUBJECTS AND METHODS: Nine cases of cancer among crew members of the ferry were reported between 2001 and 2006, six of which occurred in crew working in the engine room. During the investigated time period, 65 men had been employed in the engine room (mean age 40, range 16-65, years). Four cases were referred to our department. Medical history, personal risk factors and specific diagnoses were collected by medical examinations and from the medical files. An experienced occupational hygienist evaluated work-related exposure to carcinogens.

RESULTS: Two engine room ratings contracted lung cancer at the age of 54 and 61, respectively. Both men had been smokers for many years (33 and 45 years, respectively). One engine room rating and one electrical engineer were diagnosed with mesothelioma at the age of 61 and 63, respectively. All four had started to work in engine rooms between 1959 and 1967. Carcinogenic exposure included asbestos, with an estimated cumulative exposure of 2-5 fibreyears/mL, as well as polycyclic aromatic hydrocarbons (PAHs) and nitroarenes from oils, soot and engine exhaust.

CONCLUSIONS: For the lung cancer cases, smoking and asbestos exposure were considered clear risk factors, and PAHs and nitroarenes possible risk factors. For the mesothelioma cases, former asbestos exposure was considered a causal factor. Asbestos can still be present on ships. Steps should be taken to reduce the exposure to asbestos, PAHs and nitroarenes, and smoking.}, } @article {pmid18349460, year = {2008}, author = {Levy, AD and Arnáiz, J and Shaw, JC and Sobin, LH}, title = {From the archives of the AFIP: primary peritoneal tumors: imaging features with pathologic correlation.}, journal = {Radiographics : a review publication of the Radiological Society of North America, Inc}, volume = {28}, number = {2}, pages = {583-607; quiz 621-2}, doi = {10.1148/rg.282075175}, pmid = {18349460}, issn = {1527-1323}, mesh = {Carcinoma, Small Cell/diagnosis/pathology ; Contrast Media ; Cystadenocarcinoma, Serous/diagnosis/pathology ; Diagnosis, Differential ; *Diagnostic Imaging ; Fibrosis/diagnosis/pathology ; Humans ; Leiomyomatosis/diagnosis/pathology ; Mesothelioma/diagnosis/pathology ; Peritoneal Neoplasms/*diagnosis/pathology ; Peritoneum/anatomy & histology/pathology ; }, abstract = {Primary peritoneal tumors are uncommon lesions that arise from the mesothelial or submesothelial layers of the peritoneum. Primary malignant mesothelioma, multicystic mesothelioma, primary peritoneal serous carcinoma, leiomyomatosis peritonealis disseminata, and desmoplastic small round cell tumor are the most prominent of these rare lesions. Primary malignant mesothelioma is a highly aggressive malignancy that occurs most commonly in older men and that has a strong association with high levels of asbestos exposure. It manifests most often as diffuse sheetlike or nodular thickening of the peritoneal surfaces, but it may occasionally be a localized mass. Multicystic mesothelioma occurs most frequently in women and has benign or indolent biologic behavior in the majority of patients. It is a multilocular cystic mass that arises from the pelvic peritoneal surfaces. Primary peritoneal serous carcinoma occurs almost exclusively in women. It is histologically identical to ovarian serous carcinoma and may be indistinguishable from metastatic ovarian carcinoma at imaging studies. Leiomyomatosis peritonealis disseminata is a rare, benign proliferative process that also occurs exclusively in women and is characterized by multiple smooth muscle nodules throughout the peritoneum. Desmoplastic small round cell tumor is a highly aggressive malignancy of unknown origin that occurs most often in the peritoneal cavity of young men. This unusual group of tumors is linked together by a common site of origin and imaging manifestations that mimic those of peritoneal carcinomatosis. Knowledge of the spectrum of imaging findings in this group of primary peritoneal tumors, along with their clinical and pathologic characteristics, is important in the evaluation of patients with diffuse peritoneal disease.}, } @article {pmid18347916, year = {2008}, author = {Dogan, AU and Dogan, M and Hoskins, JA}, title = {Erionite series minerals: mineralogical and carcinogenic properties.}, journal = {Environmental geochemistry and health}, volume = {30}, number = {4}, pages = {367-381}, pmid = {18347916}, issn = {0269-4042}, mesh = {Animals ; Carcinogens, Environmental/*chemistry ; Environmental Exposure/*adverse effects ; Humans ; Lung/pathology ; Mesothelioma/etiology/prevention & control ; Pleural Neoplasms/etiology/prevention & control ; Turkey/epidemiology ; United States/epidemiology ; Zeolites/*adverse effects/*chemistry ; }, abstract = {Erionite is a human and animal carcinogen and one of the most toxic minerals known. Erionite deposits have been reported in many countries; however, it is only in the area of three villages of Cappadocia, Turkey, that environmental exposure to erionite has been demonstrated to be the cause of an epidemic of the disease mesothelioma. In the USA, no cases of mesothelioma have been reliably proven to be the result of erionite exposure, though the possibility exists. Erionite samples from three villages of the Cappadocia region were characterized mineralogically and compared with three different standards from the USA. Micro morphological details of erionite minerals using a high-resolution field-emission SEM showed that microstructures of "bundles", "fibers", and "fibrils" are important physical properties of fibrous erionite minerals. Typical lung burden of erionite and asbestos fibers were compared in terms of number of fibers. Assuming the lung burden of fibers in a human mesothelioma victim is about 1 mg, and the hazardous fibers are approximately 1 mum in diameter and 10 mum long, that milligram contains approximately 40 million asbestos and 50 million erionite fibers. These microstructures of erionite minerals draw attention to the concepts of surface area or surface-area-to-volume ratio and their relationship to the carcinogenicity of the mineral. The larger surface area creates a wider platform for mineral-cell interaction and thus more possibilities of proliferative transformation of mesothelial cells. Consequently, understanding the exact mineralogical properties will help determination of the true carcinogenic mechanism(s) of the mineral for prevention and possibly treatment of malignant mesothelioma.}, } @article {pmid18346953, year = {2008}, author = {Mastrangelo, G and Ballarin, MN and Bellini, E and Bizzotto, R and Zannol, F and Gioffrè, F and Gobbi, M and Tessadri, G and Marchiori, L and Marangi, G and Bozzolan, S and Lange, JH and Valentini, F and Spolaore, P}, title = {Feasibility of a screening programme for lung cancer in former asbestos workers.}, journal = {Occupational medicine (Oxford, England)}, volume = {58}, number = {3}, pages = {175-180}, doi = {10.1093/occmed/kqn018}, pmid = {18346953}, issn = {1471-8405}, mesh = {Adult ; *Asbestos ; Cost-Benefit Analysis ; Costs and Cost Analysis ; Feasibility Studies ; Humans ; Lung Neoplasms/*diagnostic imaging ; Male ; Mass Screening/economics/*methods ; Mesothelioma/*diagnostic imaging ; Middle Aged ; Occupational Diseases/*diagnostic imaging ; Occupational Exposure ; Pleural Diseases/diagnosis ; Radiation Dosage ; Tomography, X-Ray Computed/economics ; }, abstract = {BACKGROUND: Low-dose computed tomography (CT) has been found to detect more Stage IA lung cancer than chest x-ray.

AIMS: To investigate whether lung cancer screening with CT was effective and acceptable in former asbestos workers.

METHODS: CT scanning was carried out following the protocol previously described in the literature. A questionnaire was used to assess cumulative asbestos exposure. An economic analysis was also performed. Informed consent was obtained from all patients.

RESULTS: A total of 1119 male asbestos workers (58% of invited) were examined, of whom 65% were smokers or ex-smokers. Mean age was 57.1 years with mean cumulative exposure to asbestos of 123 fibres/ml x years. Pleural plaques were found in 375 workers (32%), while 338 workers (29%) were included in the radiological follow-up, which led to 25 biopsies (13 of lung, 9 of pleura, 3 of both) and five screen-detected lung cancers (0.4%), one in Stage I. Incidence rate was 149 per 10(5), equal to that in the male general population of similar age. The expenses for diagnosis were 1014 and 244962 Euro per screened subject and screen-detected lung cancer case, respectively.

CONCLUSIONS: Screening adherence and frequency of detection were low, while costs and radiation dose were high. In spite of a high cumulative asbestos exposure, lung cancer risk was not increased relative to the general population. The screening programme was not felt to be cost-effective from the perspective of the government as a third-party funding agency.}, } @article {pmid18338548, year = {2007}, author = {Partemi, S and De Giorgio, F}, title = {Medico-legal aspects of mesothelioma.}, journal = {Annali italiani di chirurgia}, volume = {78}, number = {5}, pages = {401-403}, pmid = {18338548}, issn = {0003-469X}, mesh = {Humans ; Italy ; *Mesothelioma/diagnosis/etiology ; *Occupational Diseases/diagnosis/etiology ; Workers' Compensation/*legislation & jurisprudence ; }, abstract = {The Authors, reviewing the Literature on asbestos-related Malignant Mesothelioma (MM), found that because of its very peculiar characteristics, the causal link between professional asbestos exposure and the development of this tumour is very difficult to define in respect to: diagnosis, causal link and individuation of possible culpable conducts. The evaluation of causal link in different medico-legal areas is studied by different criteria. In civil law the criterion of weak causality is followed to allow compensation for damages. For institutional purposes in INAIL, the definition of causal link is particularly facilitated by the legal presumption of origin. In fact it is sufficient, that asbestos-related lesions are ascertained in individuals who are or were exposed at any time of their professional life to the risk of inhaling asbestos fibres. In criminal law, the current approach of the Supreme Court is to demand evidence of strong causality, with a high logical probability and rational credibility, and beyond reasonable doubt, because criminal liability is personal as established in article 27 of the Italian Constitution. It is worth pointing out that all the levels of evidence indicated above must pass the test of scientific suitability or possibility.}, } @article {pmid18338467, year = {2007}, author = {}, title = {[Proceedings of the National Conference on Malignant Mesotheliomas in the Lower Iseo Lake Area, 22 May 2006, Iseo, Italy].}, journal = {Epidemiologia e prevenzione}, volume = {31}, number = {4 Suppl 1}, pages = {1-84}, pmid = {18338467}, issn = {1120-9763}, mesh = {Asbestos/*adverse effects ; Humans ; Italy/epidemiology ; Mesothelioma/*epidemiology/*etiology ; Occupational Diseases/*epidemiology/*etiology ; *Textile Industry ; }, } @article {pmid18336278, year = {2008}, author = {Villanova, F and Procopio, A and Rippo, MR}, title = {Malignant mesothelioma resistance to apoptosis: recent discoveries and their implication for effective therapeutic strategies.}, journal = {Current medicinal chemistry}, volume = {15}, number = {7}, pages = {631-641}, doi = {10.2174/092986708783885273}, pmid = {18336278}, issn = {0929-8673}, mesh = {Animals ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; *Apoptosis/drug effects/genetics ; Drug Resistance, Neoplasm/drug effects/genetics ; Humans ; *Mesothelioma/genetics/physiopathology/therapy ; *Pleural Neoplasms/genetics/physiopathology/therapy ; Signal Transduction/drug effects/genetics ; }, abstract = {Malignant Mesothelioma is an aggressive and fatal type of tumor. The incidence of mesothelioma has increased in the past 30 years and is now common as male cancers of the liver, bone and bladder, especially in Europe and Australia. The main risk factor is asbestos exposure even if other co-factor, such as simian virus 40 (SV40) could be implied in its etiology. Unfortunately, its incidence is expected to continue to increase for the next decades, also in rapidly industrializing countries, such as India, where it is not recognised as an occupational disease. Furthermore, some disastrous events, such as the World Trade Center Disaster, may contribute to increase future risk for mesothelioma. The treatment-resistant phenotype of mesothelioma is largely due to its ability to escape from the highly regulated apoptotic machinery. The understanding of the molecular mechanisms responsible of the malignant mesothelioma resistance to apoptosis is now advancing, allowing developing new therapeutic strategies to change the natural history and improve survival of patients. This review gives an overview of the main anti-apoptotic strategies devised by malignant mesothelioma and the therapeutic implication and opportunities for this cancer.}, } @article {pmid18332380, year = {2008}, author = {Marrett, LD and Ellison, LF and Dryer, D}, title = {Canadian cancer statistics at a glance: mesothelioma.}, journal = {CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne}, volume = {178}, number = {6}, pages = {677-678}, pmid = {18332380}, issn = {1488-2329}, mesh = {Adult ; Age Distribution ; Aged ; Asbestos/adverse effects ; Canada/epidemiology ; Cross-Sectional Studies ; Female ; Humans ; Incidence ; Lung Neoplasms/diagnosis/*epidemiology ; Male ; Mesothelioma/diagnosis/*epidemiology ; Middle Aged ; Occupational Exposure/*adverse effects ; Registries ; Risk Factors ; Sex Distribution ; Survival Analysis ; }, } @article {pmid18327171, year = {2008}, author = {Cook, A}, title = {Asbestos dressing.}, journal = {British dental journal}, volume = {204}, number = {5}, pages = {224}, doi = {10.1038/bdj.2008.174}, pmid = {18327171}, issn = {1476-5373}, mesh = {Asbestos/*toxicity ; Bandages/*adverse effects ; *Carcinogens ; Gingivectomy/*methods ; Humans ; Mesothelioma/*etiology ; }, } @article {pmid18326422, year = {2007}, author = {Roberti, S and Merler, E and Bressan, V and Fiore, AR and , }, title = {[Malignant mesothelioma in the Veneto Region (north-east of Italy), 1988-2002: incidence, geographical analysis, trends and comparison with mortality].}, journal = {Epidemiologia e prevenzione}, volume = {31}, number = {6}, pages = {309-316}, pmid = {18326422}, issn = {1120-9763}, mesh = {Asbestos/*adverse effects ; Cluster Analysis ; Confidence Intervals ; Female ; Humans ; Incidence ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology/etiology/mortality ; Pleural Neoplasms/*epidemiology/etiology/mortality ; Risk Factors ; Sex Factors ; }, abstract = {OBJECTIVE: The study assesses incidence and trend of malignant mesothelioma (MM), and mortality from primary pleural tumour (PPT) among residents of the Veneto region (North-east of Italy 4,450,000 inhabitants at the last census). The study also aims at identifying areas at high risk, by applying geographical analysis techniques.

METHOD: The results have been obtained through the activity ofa Mesothelioma Registry, established in 2001, thus collecting largely retrospective data. Incidence and trends are estimated on MM diagnosed between 1988 and 2002 by means of histological or cytological techniques. Deaths from PPT are derived through the availability of mortality records for the period 1988-1999 (latest year available). Direct age-standardization was applied to provincial rates (7 provinces), whereas standardized mortality and incidence ratios according to Kernel estimates and spatial scan statistics have been used to identify clusters at the municipality level (581 municipalities).

RESULTS AND CONCLUSIONS: the incidence of MM in the Veneto region appears similar to that of other northern Italian regions (904 new MM cases from 1988 to 2002, 650 among males, 819 pleural; age-standardized annual incidence rates x 100,000 in the period 1988-1999): 1.75 (IC 95% 1.59-1.91) among males, based on 460 cases, and 0.67 (IC 95% 0.57-0.77) among females, based on 196 cases, and displays an increasing trend among both genders. Among males incidence doubles during the study period. High risks are detected among males in a cluster formed by the city of Venice and surrounding municipalities (Standardized Incidence Ratio, SIR, for pleural mesothelioma, 1988-1999, 2.94 (p = 0.001) for the cluster based on 110 observed cases), and, in addition to Venice, in the province of Padua among females (SIR from pleural mesothelioma, 1988-1999, 1.98 (p = 0.001) for the cluster based on 95 observed cases). Mortality from TPP turns out to be higher than incidence and tends to approach incidence in more recent years; this may be explained by the increasing application of diagnostic procedures, inclusive of histopathological tests, among old patients.}, } @article {pmid18324516, year = {2008}, author = {Pierce, JS and McKinley, MA and Paustenbach, DJ and Finley, BL}, title = {An evaluation of reported no-effect chrysotile asbestos exposures for lung cancer and mesothelioma.}, journal = {Critical reviews in toxicology}, volume = {38}, number = {3}, pages = {191-214}, doi = {10.1080/10408440701845609}, pmid = {18324516}, issn = {1040-8444}, mesh = {Asbestos, Serpentine/*toxicity ; Cohort Studies ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; No-Observed-Adverse-Effect Level ; Occupational Exposure ; Risk ; Risk Assessment ; }, abstract = {Numerous investigators have suggested that there is likely to be a cumulative chrysotile exposure below which there is negligible risk of asbestos-related diseases. However, to date, little research has been conducted to identify an actual "no-effect" exposure level for chrysotile-related lung cancer and mesothelioma. The purpose of this analysis is to summarize and present all of the cumulative exposure-response data reported for predominantly chrysotile-exposed cohorts in the published literature. Criteria for consideration in this analysis included stratification of relative risk or mortality ratio estimates by cumulative chrysotile exposure. Over 350 studies were initially evaluated and subsequently excluded from the analysis due primarily to lack of cumulative exposure information, lack of information on fiber type, and/or evidence of significant exposures to amphiboles. Fourteen studies meeting the inclusion criteria were found where lung cancer risk was stratified by cumulative chrysotile exposure; four such studies were found for mesothelioma. All of the studies involved cohorts exposed to high levels of chrysotile in mining or manufacturing settings. The preponderance of the cumulative "no-effects" exposure levels for lung cancer and mesothelioma fall in a range of approximately 25-1,000 fibers per cubic centimeter per year (f/cc-yr) and 15-500 f/cc-yr, respectively, and a majority of the studies did not report an increased risk at the highest estimated exposure. Sources of uncertainty in these values include errors in the cumulative exposure estimates, conversion of dust counts to fiber data, and use of national age-adjusted mortality rates. Numerous potential biases also exist. For example, smoking was rarely controlled for and amphibole exposure did in fact occur in a majority of the studies, which would bias many of the reported "no-effect" exposure levels towards lower values. However, many of the studies likely lack sufficient power (e.g., due to small cohort size) to assess whether there could have been a significant increase in risk at the reported no-observed-adverse-effects level (NOAEL); additional statistical analyses are required to address this source of bias and the attendant influence on these values. The chrysotile NOAELs appear to be consistent with exposure-response information for certain cohorts with well-established industrial hygiene and epidemiology data. Specifically, the range of chrysotile NOAELs were found to be consistently higher than upper-bound cumulative chrysotile exposure estimates that have been published for pre-1980s automobile mechanics (e.g., 95th percentile of 2.0 f/ cc-yr), an occupation that historically worked with chrysotile-containing friction products yet has been shown to have no increased risk of asbestos-related diseases. While the debate regarding chrysotile as a risk factor for mesothelioma will likely continue for some time, future research into nonlinear, threshold cancer risk models for chrysotile-related respiratory diseases appears to be warranted.}, } @article {pmid18323865, year = {2008}, author = {Toyooka, S and Kishimoto, T and Date, H}, title = {Advances in the molecular biology of malignant mesothelioma.}, journal = {Acta medica Okayama}, volume = {62}, number = {1}, pages = {1-7}, doi = {10.18926/AMO/30990}, pmid = {18323865}, issn = {0386-300X}, mesh = {DNA Methylation ; Epigenesis, Genetic ; *Gene Expression Regulation, Neoplastic ; Humans ; Mesothelioma/*genetics ; Mutation ; Neoplasms, Glandular and Epithelial/*genetics ; Pleural Neoplasms/*genetics ; }, abstract = {Malignant mesothelioma (MM) is a highly aggressive tumor with a dismal prognosis. The incidence of MM is increasing as a result of widespread exposure to asbestos. As for the molecular alterations that occur in MM, chromosome alterations including homo-deletion of the P16 and P14 genes located in the 9p21 are well known. Mutations are rare in the P53 and Ras genes, which are frequently present in epithelial solid tumors. However, mutations are frequently present in the neurofibromatosis type 2 gene. Epigenetic alterations including DNA methylation have been found in the MM, the profile of which is different from that of lung cancer, although differential diagnosis is sometimes clinically difficult. As in other malignant tumors, genes that are related to immortalization, proliferation, metastasis, angiogenesis, and anti-apoptosis are also overexpressed in MM, contributing to its malignant phenotype. It is of interest that simian virus 40 has been implicated to be one of the causative factors of MM in western countries. Although the causative role of asbestos is well-known in MM, much less information is available for MM than for other malignant tumors regarding the molecular alterations that occur in the disease. In terms of future tasks, it will be necessary to apply the knowledge that is learned about molecular alterations to clinical practice and to further elucidate the pathogenesis of MM with extensive research.}, } @article {pmid18320733, year = {2008}, author = {Greenberg, M}, title = {The defence of chrysotile, 1912-2007.}, journal = {International journal of occupational and environmental health}, volume = {14}, number = {1}, pages = {57-66}, doi = {10.1179/oeh.2008.14.1.57}, pmid = {18320733}, issn = {1077-3525}, mesh = {Asbestos, Serpentine/*history/poisoning ; Asbestosis/epidemiology/etiology/*history ; Canada/epidemiology ; Health Knowledge, Attitudes, Practice ; Health Policy/legislation & jurisprudence ; History, 20th Century ; History, 21st Century ; Humans ; Lung Neoplasms/epidemiology/etiology ; Male ; Mesothelioma/epidemiology/etiology ; Mining/history ; Occupational Exposure/legislation & jurisprudence ; }, abstract = {The commercial exploitation of asbestos may be dated from the late 1870s, when Canada was the major world source. Reports of severe and fatal respiratory disease in workers in asbestos factories appeared in Britain (1898, 1906), and in France (1906) and Italy (1908). In 1912 the Canadian Department of Labour denied that the health of Quebec's millers and miners was affected. A series of denials appeared for over 40 years, until in 1955 a Thetford Mines medical officer reported finding that between 1945 and 1953, among some 4,000 asbestos workers 128 had asbestosis of various degrees of severity, 121 diagnosed radiographically, and 33 confirmed at autopsy. Although a committee of inquiry into health in the asbestos industry (1976), and a Royal Commission on health and safety arising in the use of asbestos in Ontario (1984) confirmed that disease had occurred, these findings were to have no adverse effects on asbestos exports. Rather, the inquiries constituted elements in the industry's successful public relations exercise that continues to operate to this day. Even when an increasing number of national bodies have legislated for total bans on asbestos use, a policy with which all the international bodies concerned with public health agree, the Canadian PR apparatus continues to be able to call on physicians and scientists prepared to oppose the consensuses reached by the independent advisors to these bodies.}, } @article {pmid18316566, year = {2008}, author = {Shiomi, K and Hagiwara, Y and Sonoue, K and Segawa, T and Miyashita, K and Maeda, M and Izumi, H and Masuda, K and Hirabayashi, M and Moroboshi, T and Yoshiyama, T and Ishida, A and Natori, Y and Inoue, A and Kobayashi, M and Sakao, Y and Miyamoto, H and Takahashi, K and Hino, O}, title = {Sensitive and specific new enzyme-linked immunosorbent assay for N-ERC/mesothelin increases its potential as a useful serum tumor marker for mesothelioma.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {14}, number = {5}, pages = {1431-1437}, doi = {10.1158/1078-0432.CCR-07-1613}, pmid = {18316566}, issn = {1078-0432}, mesh = {Aged ; Aged, 80 and over ; Animals ; Antibodies, Monoclonal/immunology ; Asbestos ; Asbestosis/blood/diagnosis ; Biomarkers, Tumor/*blood ; Blotting, Western ; CHO Cells ; Case-Control Studies ; Cells, Cultured ; Cricetinae ; Cricetulus ; *Enzyme-Linked Immunosorbent Assay ; Female ; GPI-Linked Proteins ; Humans ; Lung Neoplasms/blood/diagnosis ; Male ; Membrane Glycoproteins/*blood ; Mesothelin ; Mesothelioma/*blood/diagnosis ; Mice ; Middle Aged ; Pleural Neoplasms/blood/diagnosis ; Sensitivity and Specificity ; }, abstract = {BACKGROUND: Because mesothelioma initially progresses on the surface of the pleura and peritoneum without forming masses, it has been difficult to diagnose at an early stage. It would be very useful to identify a tumor marker that could be used for screening to enable more diagnoses to be made at an early, treatable stage.

MATERIALS AND METHODS: We had previously identified N-ERC/mesothelin as a potential biomarker for mesothelioma. In the current work, we used a newly developed ELISA system to gain data on N-ERC/mesothelin levels in various clinical settings. A total of 102 healthy volunteers were recruited. In addition, 39 patients were diagnosed with mesothelioma, 53 patients were diagnosed with diseases that should be distinguished from mesothelioma, and 201 subjects were diagnosed with asbestos-related nonmalignant diseases (including simple exposure to asbestosis) who were treated at any of the cooperating hospitals were enrolled.

RESULTS: Serum N-ERC/mesothelin levels measured by a new ELISA system showed that the median values from patients with mesothelioma were extremely high compared with levels obtained from other patients. Analysis in terms of histologic type showed that serum levels of N-ERC/mesothelin were elevated in epithelioid type mesothelioma, especially. In four important models of clinical settings, the sensitivity and specificity of N-ERC/mesothelin were about 71% to 90% and 88% to 93%, respectively.

CONCLUSION: N-ERC/mesothelin is a very promising tumor marker for mesothelioma, especially epithelioid mesothelioma.}, } @article {pmid18310086, year = {2008}, author = {Christensen, BC and Godleski, JJ and Marsit, CJ and Houseman, EA and Lopez-Fagundo, CY and Longacker, JL and Bueno, R and Sugarbaker, DJ and Nelson, HH and Kelsey, KT}, title = {Asbestos exposure predicts cell cycle control gene promoter methylation in pleural mesothelioma.}, journal = {Carcinogenesis}, volume = {29}, number = {8}, pages = {1555-1559}, pmid = {18310086}, issn = {1460-2180}, support = {CA126939/CA/NCI NIH HHS/United States ; P42ES05947/ES/NIEHS NIH HHS/United States ; P42 ES005947/ES/NIEHS NIH HHS/United States ; T32ES007155/ES/NIEHS NIH HHS/United States ; R01 CA126939/CA/NCI NIH HHS/United States ; T32 ES007155/ES/NIEHS NIH HHS/United States ; }, mesh = {Asbestos/*toxicity ; *Body Burden ; Cell Cycle/*genetics ; DNA Methylation/drug effects ; DNA, Neoplasm/drug effects/*genetics ; Environmental Exposure ; Humans ; Incidence ; Mesothelioma/epidemiology/*genetics ; Neoplasm Proteins/*genetics ; Pleural Neoplasms/epidemiology/*genetics ; Promoter Regions, Genetic/*drug effects ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rapidly fatal tumor with increasing incidence worldwide responsible for many thousands of deaths annually. Although there is a clear link between exposure to asbestos and mesothelioma, and asbestos is known to be both clastogenic and cytotoxic to mesothelial cells, the mechanisms of causation of MPM remain largely unknown. However, there is a rapidly emerging literature that describes inactivation of a diverse array of tumor suppressor genes (TSGs) via promoter DNA CpG methylation in MPM, although the etiology of these alterations remains unclear. We studied the relationships among promoter methylation silencing, asbestos exposure, patient demographics and tumor histology using a directed approach; examining six cell cycle control pathway TSGs in an incident case series of 70 MPMs. Promoter hypermethylation of APC, CCND2, CDKN2A, CDKN2B, HPPBP1 and RASSF1 were assessed. We observed significantly higher lung asbestos body burden if any of these cell cycle genes were methylated (P < 0.02), and there was a significant trend of increasing asbestos body counts as the number of methylated cell cycle pathway genes increased from 0 to 1 to >1 (P < 0.005). This trend of increasing asbestos body count and increasing number of methylated cell cycle pathway genes remained significant (P < 0.05) after controlling for age, gender and tumor histology. These data suggest a novel tumorigenic mechanism of action of asbestos and may contribute to the understanding of precisely how asbestos exposure influences the etiology and clinical course of malignant mesothelioma.}, } @article {pmid19568885, year = {2008}, author = {Nakano, T}, title = {Current therapies for malignant pleural mesothelioma.}, journal = {Environmental health and preventive medicine}, volume = {13}, number = {2}, pages = {75-83}, pmid = {19568885}, issn = {1342-078X}, abstract = {Mesothelioma is a highly lethal tumor derived from mesothelial cells, and its global incidence is increasing because of widespread exposure of numerous individuals to asbestos in the last 50 years. Mesothelioma is largely untreatable with any of the therapeutic modalities. Recently, a novel multitargeted antifolate pemetrexed has shown promising activity against malignant pleural mesothelioma, producing response rates of up to 40% when used in combination with cisplatin. In a large phase III study, use of a combination of pemetrexed and cisplatin was associated with significantly improved survival time and with greater antitumor activity compared with cisplatin alone. This combination also gave a significant response rate of approximately 50% in patients with epithelioid malignant pleural mesothelioma. These clinical benefits of pemetrexed-cisplatin doublet have changed the perception of mesothelioma chemotherapy. Other combinations, including gemcitabine in combination with cisplatin, have also shown encouraging response rates. Prognosis depends on gender, clinical stage of the tumor, histological subtype, platelet count, leukocyte counts, and performance status. Radiotherapy can palliate mesothelioma patients with chest pain, and has been indicated to be of benefit for the prevention of malignant seeding along the tract of a chest tube or needle biopsy. Trimodality treatment using extrapleural pneumonectomy, radiation and chemotherapy has shown promising therapeutic value. The development of chemotherapeutic regimens and the favorable outcomes of trimodality have led to new combined modality trials. In Japan, multicenter national trials against mesothelioma will begin in the near future.}, } @article {pmid19568884, year = {2008}, author = {Hino, O and Maeda, M}, title = {Diagnostic tumor marker of asbestos-related mesothelioma.}, journal = {Environmental health and preventive medicine}, volume = {13}, number = {2}, pages = {71-74}, pmid = {19568884}, issn = {1342-078X}, abstract = {Mesothelioma is an aggressive tumor arising from the mesothelium, and is usually associated with previous exposure to asbestos. The incubation period of the tumor may be described as 30-40 years, and the prognosis is dismal. We previously discovered the Erc (Expressed in renal carcinoma) gene in the Eker rat model (Tsc2 gene mutant) and it was a homolog of the human mesothelin/MPF gene. We developed a novel ELISA system (N-ERC/mesothelin). Recently, we found that N-ERC/mesothelin was a potentially useful diagnostic marker for asbestos-related mesothelioma.}, } @article {pmid19568883, year = {2008}, author = {Sekido, Y}, title = {Molecular biology of malignant mesothelioma.}, journal = {Environmental health and preventive medicine}, volume = {13}, number = {2}, pages = {65-70}, pmid = {19568883}, issn = {1342-078X}, abstract = {Human malignancies develop via a multi-step that involves the accumulation of several key gene alterations with associated genetic and epigenetic events. Although malignant mesothelioma (MM) has been demonstrated to be clearly correlated with asbestos exposure, it remains poorly understood how asbestos fibers confer key gene alterations and induce cellular transformation in normal mesothelial cells, which results in the acquisition of malignant phenotypes, including deregulated cell proliferation and invasion. Malignant mesothelioma presents with the frequent inactivation of tumor suppressor genes of p16(INK4a)/p14(ARF) on chromosome 9p21 and neurofibromatosis type 2 (NF2) on chromosome 22q12, with the latter being responsible for the NF2 familial cancer syndrome. In contrast, MM shows infrequent mutation of the p53 gene, which is one of the most frequently mutated tumor suppressor genes in human malignancies. Genetic abnormalities of oncogenes have also been studied in MM, but no frequent mutations have been identified, including the epidermal growth factor receptor (EGFR) and K-RAS genes. Recent studies have suggested the activation of other receptor tyrosine kinases, including Met, and the deregulations of mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase (PI3K)-AKT signaling cascades, although the alterations responsible for their activation are still not clear. Thus, further genome-wide studies of genetic and epigenetic alterations as well as detailed analyses of deregulated signaling cascades in MM are necessary to determine the molecular mechanisms of MM, which would also provide some clues for establishing a new molecular target therapy for MM.}, } @article {pmid19568882, year = {2008}, author = {Inai, K}, title = {Pathology of mesothelioma.}, journal = {Environmental health and preventive medicine}, volume = {13}, number = {2}, pages = {60-64}, pmid = {19568882}, issn = {1342-078X}, abstract = {The incidence of mesothelioma has been gradually increasing in Japan, and the underlying factor for this is considered to be the increase in the amount of asbestos imported into Japan between 1960 and 1975. Mesothelioma can be roughly divided into localized and diffuse types, but the former is extremely rare. In making a diagnosis of mesothelioma, it is important to confirm the location of tumor and the specific gross findings before histological examination. Mesothelioma can be categorized histologically as epithelioid type, sarcomatoid type, biphasic type, desmoplastic type, among others. It can take many forms; consequently, there are many diseases to be differentiated when the diagnosis of mesothelioma is based on histological analyses. Immunohistochemical stains are useful for making a diagnosis, but the correct combination of antibodies as positive or negative markers should be selected and a comprehensive assessment of the staining results is necessary. The accuracy of the pathological diagnosis is very important to the patients because they can be receive official compensation or relief when the diagnosis of mesothelioma is confirmed. Under present conditions, both clinicians and pathologists must make a concerted effort to improve the accuracy of the diagnosis of mesothelioma.}, } @article {pmid19568881, year = {2008}, author = {Miura, Y and Nishimura, Y and Maeda, M and Murakami, S and Hayashi, H and Fukuoka, K and Kishimoto, T and Nakano, T and Otsuki, T}, title = {Immunological alterations found in mesothelioma patients and supporting experimental evidence.}, journal = {Environmental health and preventive medicine}, volume = {13}, number = {2}, pages = {55-59}, pmid = {19568881}, issn = {1342-078X}, abstract = {It is common knowledge that exposure to asbestos causes asbestos-related diseases, such as asbestosis, lung cancer and malignant mesothelioma, not only in people who have had long-term contact with asbestos in their work environment but also in residents living near factories that handle asbestos. Since the summer of 2005, these revelations turned into a large medical problem and caused and social unrest. We have focused on the immunological effects of both asbestos and silica on the human immune system. In this brief review, we introduce immunological alterations found in patients with malignant mesothelioma and describe the experimental background in which these were found. Analyzing the immunological effects of asbestos may improve our understanding of the biological effects of asbestos.}, } @article {pmid19568880, year = {2008}, author = {Otsuki, T}, title = {Asbestos and malignant mesothelioma: foreword. Reviews of a symposium entitled "Malignant Mesothelioma" organized by the Study Group on Fibrous and Particulate Substances of the 77th Annual Meeting of the Japanese Society for Hygiene, 2007.}, journal = {Environmental health and preventive medicine}, volume = {13}, number = {2}, pages = {53-54}, doi = {10.1007/s12199-007-0013-x}, pmid = {19568880}, issn = {1342-078X}, } @article {pmid18303189, year = {2008}, author = {Takagi, A and Hirose, A and Nishimura, T and Fukumori, N and Ogata, A and Ohashi, N and Kitajima, S and Kanno, J}, title = {Induction of mesothelioma in p53+/- mouse by intraperitoneal application of multi-wall carbon nanotube.}, journal = {The Journal of toxicological sciences}, volume = {33}, number = {1}, pages = {105-116}, doi = {10.2131/jts.33.105}, pmid = {18303189}, issn = {1880-3989}, mesh = {Animals ; Carcinogens/administration & dosage/*toxicity ; Gastrointestinal Tract/drug effects/pathology ; Genes, p53/genetics ; Injections, Intraperitoneal ; Kidney ; Male ; Mesothelioma/*chemically induced/pathology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Nanotubes, Carbon/*toxicity ; Peritoneal Neoplasms/*chemically induced/pathology ; Peritoneum/drug effects/pathology ; }, abstract = {Nanomaterials of carbon origin tend to form various shapes of particles in micrometer dimensions. Among them, multi-wall carbon nanotubes (MWCNT) form fibrous or rod-shaped particles of length around 10 to 20 micrometers with an aspect ratio of more than three. Fibrous particles of this dimension including asbestos and some man-made fibers are reported to be carcinogenic, typically inducing mesothelioma. Here we report that MWCNT induces mesothelioma along with a positive control, crocidolite (blue asbestos), when administered intraperitoneally to p53 heterozygous mice that have been reported to be sensitive to asbestos. Our results point out the possibility that carbon-made fibrous or rod-shaped micrometer particles may share the carcinogenic mechanisms postulated for asbestos. To maintain sound activity of industrialization of nanomaterials, it would be prudent to implement strategies to keep good control of exposure to fibrous or rod-shaped carbon materials both in the workplace and in the future market until the biological/ carcinogenic properties, especially of their long-term biodurability, are fully assessed.}, } @article {pmid18302902, year = {2008}, author = {Zhou, JS}, title = {[A case of asbestos induced malignant mesothelioma].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {26}, number = {1}, pages = {63}, pmid = {18302902}, issn = {1001-9391}, mesh = {Adult ; Asbestos/*adverse effects ; Humans ; Male ; Mesothelioma/*chemically induced ; Occupational Diseases/*chemically induced ; Pleural Neoplasms/chemically induced ; }, } @article {pmid18301454, year = {2006}, author = {Ismail, HM and Nouh, MA and Abulkheir, IL and Abd El-Rahman, Ael-R and Tawfik, HN}, title = {Pleural mesothelioma: diagnostic problems and evaluation of prognostic factors.}, journal = {Journal of the Egyptian National Cancer Institute}, volume = {18}, number = {4}, pages = {303-310}, pmid = {18301454}, issn = {1110-0362}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis/metabolism ; Calbindin 2 ; Carcinoembryonic Antigen/metabolism ; Female ; Humans ; Immunohistochemistry ; Keratin-5/metabolism ; Keratin-6/metabolism ; Male ; Mesothelioma/*diagnosis/metabolism/mortality ; Middle Aged ; Pleural Neoplasms/*diagnosis/metabolism/mortality ; Prognosis ; Proliferating Cell Nuclear Antigen/metabolism ; S100 Calcium Binding Protein G/metabolism ; Survival Analysis ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) in Egypt is mainly attributed to an environmental origin i.e exposure to asbestos, with a high incidence in women and young adults. Immunohistochemistry and ultrastructural features aid in the diagnosis. The p27Kip1 is a kinase inhibitor protein acting as a cell cycle regulator and a putative tumor suppressor gene playing a critical role in the pathogenesis of several human neoplasms.

AIM: A clinicopathologic, immunohistochemical and ultrastructural study of mesothelioma in Egyptian patients, with identification of different prognostic factors.

MATERIAL AND METHODS: Sixty-one cases of MPM were collected from the department of pathology at the NCI, Cairo. Cases were stained by monoclonal antibodies against CK5/6, calretinin, vimentin, CD15, CEA and p27.

RESULTS: More than half (57.4%) of the patients were residents in endemic areas; 50.8% were of epithelioid type. CK5/6 was positive in 45 (73.8%) cases, 39 (63.9%) cases were positive for vimentin, 49 (80.3%) cases were positive for calretinin. One case showed a focal weak positive reaction to CD15. None of the cases stained for CEA. There was a statistically significant relation between p27 expression and the histopathologic type (p=0.02) between overall survival and age (p=0.01), histopathologic type (p=0.02) and stage (p=0.006).

CONCLUSION: MPM is an increasing disaster in Egypt which is underestimated and neglected. A panel of immunohistochemical markers should be used for proper evaluation. p27 has proven to be a potential biologic prognostic marker for mesothelioma and more studies as regard its significance are recommended on a larger number.}, } @article {pmid18294289, year = {2008}, author = {Hagiwara, Y and Hamada, Y and Kuwahara, M and Maeda, M and Segawa, T and Ishikawa, K and Hino, O}, title = {Establishment of a novel specific ELISA system for rat N- and C-ERC/mesothelin. Rat ERC/mesothelin in the body fluids of mice bearing mesothelioma.}, journal = {Cancer science}, volume = {99}, number = {4}, pages = {666-670}, pmid = {18294289}, issn = {1349-7006}, mesh = {Animals ; Antibodies, Monoclonal ; Antibody Specificity ; Asbestos/toxicity ; Body Fluids/*chemistry ; Enzyme-Linked Immunosorbent Assay/*methods ; Epitope Mapping ; Flow Cytometry ; GPI-Linked Proteins ; Immunohistochemistry ; Membrane Glycoproteins/*analysis/chemistry/genetics ; Mesothelin ; Mesothelioma/chemically induced/*diagnosis ; Mice ; Mice, Nude ; Pleural Neoplasms/chemically induced/*diagnosis ; Rats ; }, abstract = {Mesothelioma is a type of malignant tumor that most commonly arises from the pleural or peritoneal membrane and is usually associated with previous exposure to asbestos. In humans, ERC/mesothelin is expressed on the normal mesothelium and in some cancers such as mesothelioma or ovarian carcinoma. Recently, several enzyme-linked immunosorbent assay (ELISA) systems for ERC/mesothelin have been developed, the reported usefulness of which has been assessed and demonstrated as a diagnostic tool. However, the basic roles or physiological functions of, and relationship between, ERC/mesothelin and asbestos exposure-mediated carcinogenesis remain to be resolved. In order to elucidate the precise mechanism, animal models of mesothelioma are desperately needed. In this study, we consider the development of a novel specific ELISA system for not only rat N-ERC/mesothelin but also C-ERC/mesothelin, and the first data on the presence of rat ERC/mesothelin in the body fluids of rat malignant mesothelioma-bearing nude mice. The transplanted mice have revealed the higher concentrations of rat N-ERC/mesothelin in the blood and ascites than C-ERC/mesothelin. We hope these novel ELISA systems are useful in the rat model system to clarify the mechanism of asbestos-induced carcinogenesis and to develop new effective drugs for mesothelioma.}, } @article {pmid18293699, year = {2007}, author = {Scripcariu, V and Dajbog, E and Radu, I and Ferariu, D and Pricop, A and Grigoraş, M and Dragomir, C}, title = {[Malignant peritoneal mesothelioma tumours. Evolution, treatment, prognosis].}, journal = {Revista medico-chirurgicala a Societatii de Medici si Naturalisti din Iasi}, volume = {111}, number = {3}, pages = {673-677}, pmid = {18293699}, issn = {0048-7848}, mesh = {Antineoplastic Agents/therapeutic use ; Cisplatin/therapeutic use ; Humans ; Male ; Mesothelioma/*diagnosis/drug therapy/pathology/surgery/*therapy ; *Neoplasm Recurrence, Local ; Peritoneal Neoplasms/*diagnosis/drug therapy/pathology/surgery/*therapy ; Prognosis ; Reoperation ; }, abstract = {Malignant mesothelioma of the peritoneum is a rare neoplasm with a rapidly fatal course. The median survival range is from 5 to 12 months in untreated cases with little improvement seen in patients receiving multimodality therapy. Although most cases occur in the fifth and sixth decades, peritoneal mesothelioma can be seen in any age group. Approximately 30% of all mesotheliomas arise solely from the peritoneum. Asbestos exposure, primarily of the crocidolite variety, has been implicated in the pathogenesis of this malignancy, as was established in South Africa in the 1960s. Half of reported cases have a history of asbestos exposure. The diagnosis of peritoneal mesothelioma is often delayed, in part because of the usually long latent period (peaking at 40-45 years from the time of initial exposure to asbestos) and because the common presenting symptoms of weight loss, usually with a full abdomen, malaise, and abdominal discomfort, are mild and nonspecific. This paper aim is to present a case report regarding a patient diagnosed with malignant peritoneal mesothelioma with an unpredictable evolution.}, } @article {pmid18235409, year = {2007}, author = {Porret, E and Madelaine, J and Galateau-Sallé, F and Bergot, E and Zalcman, G}, title = {[Epidemiology, molecular biology, diagnostic and therapeutic strategy of malignant pleural mesothelioma in 2007 - an update].}, journal = {Revue des maladies respiratoires}, volume = {24}, number = {8 Pt 2}, pages = {6S157-64}, pmid = {18235409}, issn = {0761-8425}, mesh = {Humans ; *Mesothelioma/diagnosis/epidemiology/genetics/therapy ; Molecular Biology ; *Pleural Neoplasms/diagnosis/epidemiology/genetics/therapy ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare tumour due to occupational asbestos exposure. The incidence of MPM will continue to increase until 2020-2030. The incidence reaches 100 cases/million/year in occupationally exposed populations as opposed to 1 case/million/year in the general population, leading to 800 to 1,000 cases per year in France. The molecular carcinogenesis of MPM is incompletely understood but alterations to genes NF2, c-met, WT1 RASSF and p16 have been described. These genes are involved in cell invasion and motility, cell division and apoptosis control. Histological diagnosis remains difficult and depends on immunohistochemical analysis as described by the French Mesopath group. Clinical diagnosis relies on thoracoscopy and large pleural biopsies, with increasing use of CT-PET for the evaluation of disease extent. Therapeutic strategy includes prophylactic irradiation following drainage or thoracoscopy to prevent tumour nodule development along drainage channels and puncture sites. In selected patients, extensive extra-pleural pneumonectomy can be performed with curative intent. First line chemotherapy is based on a combination of pemetrexed and cisplatin that has demonstrated an improvement in overall survival and quality of life in phase 3 trials. Antiangiogenic agents such as bevacizumab (Avastatin) may be of interest but need to be tested in phase 3 trials. The Mesothelioma Avastatin Pemetrexed Study (MAPS) is ongoing, coordinated by the French Thoracic Cancer Intergroup (IFCT).}, } @article {pmid18281122, year = {2008}, author = {Roe, OD and Creaney, J and Lundgren, S and Larsson, E and Sandeck, H and Boffetta, P and Nilsen, TI and Robinson, B and Kjaerheim, K}, title = {Mesothelin-related predictive and prognostic factors in malignant mesothelioma: a nested case-control study.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {61}, number = {2}, pages = {235-243}, doi = {10.1016/j.lungcan.2007.12.025}, pmid = {18281122}, issn = {0169-5002}, mesh = {Adolescent ; Adult ; Age Factors ; Antigens, Neoplasm/*blood ; Asbestos/adverse effects ; Biomarkers, Tumor/*blood ; Case-Control Studies ; Child ; Child, Preschool ; Female ; GPI-Linked Proteins ; Humans ; Infant ; Intracellular Signaling Peptides and Proteins ; Keratin-19 ; Keratins/*blood ; Male ; Membrane Glycoproteins/*blood ; Mesothelin ; Mesothelioma/blood/*diagnosis/etiology/mortality/pathology ; Occupational Exposure/adverse effects ; Peritoneal Neoplasms/blood/*diagnosis/etiology/mortality/pathology ; Pleural Neoplasms/blood/*diagnosis/etiology/mortality/pathology ; Prognosis ; Proteins/*metabolism ; Survival Analysis ; }, abstract = {Soluble mesothelin-related protein (SMRP) in serum is potentially a sensitive marker of malignant mesothelioma (MM) diagnosis and progression, and may be useful as screening marker. Mesothelin expression in tumors is regarded as a sensitive marker for diagnosis and disease progression, and is a candidate prognostic marker. Levels of SMRP, CA125 and CYFRA 21-1 in pre-diagnostic (1-30 years) serum samples from 47 mesothelioma cases and 141 matched controls were analysed. Mesothelin expression in tumors was assessed. The association between biomarker level and mesothelioma risk and survival was analysed, adjusting for asbestos exposure. Survival related to tumor mesothelin expression, age, sex, histological type, location, asbestos exposure and pre-clinical SMRP was analysed. There was no significant association between biomarker levels and mesothelioma risk when analysed as continuous variables or as tertiles. Biomarker levels <10, 10-19 and >or=20 years before diagnosis were not significantly associated to mesothelioma risk. Mesothelin expressed in >50% of tumor cells was seen in 36 of 47 (77%) tumors. Mesothelin expression in <50% of tumor cells was a significant negative prognostic marker in all cases of malignant mesothelioma (median survival=6 months vs. 12 months, hazard ratio (HR)=2.49, 95%CI 1.17-5.27), and also when only epithelial mesothelioma was analysed (median=6 months vs. 14 months, HR=2.36, 95%CI 1.07-5.22). When adjusted for age and gender, the prognosis was still dismal, but non-significant (HR=1.85, 95%CI 0.85-4.05). High age (>65 years) was an independent negative prognostic factor that was related to both mesothelin expression and asbestos exposure. Mesothelioma of the epithelial type of the peritoneum had a significantly longer survival than epithelial type in pleura and was also related to mesothelin expression.}, } @article {pmid18280176, year = {2008}, author = {Small, GR and Nicolson, M and Buchan, K and Broadhurst, P}, title = {Pericardial malignant mesothelioma: a latent complication of radiotherapy?.}, journal = {European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery}, volume = {33}, number = {4}, pages = {745-747}, doi = {10.1016/j.ejcts.2007.12.024}, pmid = {18280176}, issn = {1010-7940}, mesh = {Breast Neoplasms/*radiotherapy ; Diagnosis, Differential ; Fatal Outcome ; Female ; Heart Neoplasms/*etiology ; Humans ; Mesothelioma/*etiology ; Middle Aged ; Neoplasms, Radiation-Induced/*etiology ; Pericarditis, Constrictive/etiology ; *Pericardium ; Radiotherapy/adverse effects ; }, abstract = {Pericardial diseases can be difficult to differentiate from myocardial conditions. Diagnosis can be challenging and often requires the use of different imaging modalities. Here, we describe a case which presented with common cardiac symptoms which were shown to be the result of a rare condition. A 62-year-old lady presented with left femoral artery embolism. Post-embolectomy she developed cardiac failure. Three months previously an acellular, sterile pericardial effusion had been drained. In 1993 a left mastectomy and axillary node clearance was performed for breast cancer. Adjuvant chemotherapy and radiotherapy were administered. Examination revealed a raised jugular venous pressure (JVP) with rapid Y descent and Kussmaul's sign. CT chest and abdomen found no recurrence of breast carcinoma. Cardiac MRI demonstrated thickened pericardium. At cardiac catheterisation haemodynamic responses consistent with constrictive pericarditis were seen. Pericardiectomy was performed. Histology revealed pericardial epithelioid malignant mesothelioma. 18-FDG-PET CT post-operatively was negative in the pericardium and pleura. Chemotherapy with pemetrexed and carboplatin was given. The patient died 9 months after presentation. Radiotherapy and asbestos exposure are both associated with pericardial mesothelioma and the aetiology in this case was not clear. The condition carries a poor prognosis and is invariable fatal although newer chemotherapeutic regimens have prolonged survival times.}, } @article {pmid18279069, year = {2008}, author = {Kaufman, AJ and Pass, HI}, title = {Current concepts in malignant pleural mesothelioma.}, journal = {Expert review of anticancer therapy}, volume = {8}, number = {2}, pages = {293-303}, doi = {10.1586/14737140.8.2.293}, pmid = {18279069}, issn = {1744-8328}, mesh = {Chemotherapy, Adjuvant ; Combined Modality Therapy ; Diagnostic Imaging/methods ; Female ; Humans ; Immunohistochemistry ; Male ; Mesothelioma/*mortality/pathology/*therapy ; Neoplasm Staging ; Pleural Neoplasms/*mortality/pathology/*therapy ; Prognosis ; Radiotherapy, Adjuvant ; Risk Assessment ; Survival Analysis ; Thoracic Surgical Procedures/methods ; Treatment Outcome ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare but lethal cancer associated with asbestos exposure. Worldwide, the incidence of MPM is expected to increase over the next 20 years. The molecular and genetic profiling of MPM tumors and patients, and improved understanding of the pathogenesis of MPM may lead to novel diagnostic, preventative and therapeutic strategies. Treatment options for MPM remain limited and no consensus exists at this time. Multimodality therapy that combines surgery, chemotherapy and radiation offers the best chance for long-term survival in select patients.}, } @article {pmid18274232, year = {2007}, author = {Mensi, C and Termine, L and Canti, Z and Rivolta, G and Riboldi, L and Pesatori, AC and Chiappino, G}, title = {[The Lombardy Mesothelioma Register, Regional Operating Centre (ROC) of National Mesothelioma Register: organizational aspects].}, journal = {Epidemiologia e prevenzione}, volume = {31}, number = {5}, pages = {283-289}, pmid = {18274232}, issn = {1120-9763}, mesh = {Asbestosis/complications/*epidemiology ; Female ; Hospitals, District ; Humans ; Incidence ; Italy/epidemiology ; Male ; Mesothelioma/diagnosis/*epidemiology/etiology ; Occupational Diseases/*epidemiology/etiology ; Pleural Neoplasms/diagnosis/*epidemiology/etiology ; Population Surveillance ; Practice Guidelines as Topic ; *Registries ; Retrospective Studies ; Surveys and Questionnaires ; }, abstract = {The Lombardy Mesothelioma Register (LMR) collects all incident cases of Malignant Mesothelioma (MM) occurring since January 1, 2000 in residents of the Lombardy Region. For each "possible case" reported to the Registry by Lombardy hospitals, diagnosis is ascertained through examination of clinical records (including histology reports) according to ISPESL Guidelines. For confirmed cases, a standardized questionnaire is administered to the subject or next-of-kin in order to verify the possible sources of asbestos exposure in his/her lifetime. A panel composed of industrial hygienists, occupational health physicians and occupational epidemiologists evaluate asbestos exposure in the workplace and environmental settings. Case ascertainment completeness is routinely verified using other sources such as hospital discharge records and death certificates coded as 163 (ICD IX). In the period 2000-2004, 1563 cases were collected, of whom 887 have been evaluated: the diagnosis was confirmed for 626 (70.6%) 9 out of 887 evaluated cases. The age and gender standardized incidence rate for pleural mesothelioma in the Lombardy Region, in the year 2000 (the only one with completed data), was 2.4 (males 3.7; females 1.4) per 100,000 residents/year The 70.5% of certain and probable MM has an asbestos exposure, in particular the 64.5% of cases has an occupational exposure. The experience gathered over the years by the LMR has allowed to implement an efficient information network among different institutions and health services. In addition practical skills have been gained in processing epidemiological data, a useful tool to address new scientific hypothesis and to plan ad-hoc researches. In our experience the LMR represents a potential resource transferable to the epidemiological surveillance of different occupational tumours (i.e. sino-nasal cancers).}, } @article {pmid18247225, year = {2008}, author = {Carbone, RG and Terracini, B and Marinaccio, A and Montanaro, F and Shah, P}, title = {Asbestos, pleural mesothelioma,and mortality in Italy.}, journal = {Journal of occupational and environmental hygiene}, volume = {5}, number = {4}, pages = {D55-6}, doi = {10.1080/15459620801888107}, pmid = {18247225}, issn = {1545-9632}, mesh = {Asbestos/*adverse effects/supply & distribution ; Female ; Humans ; Italy/epidemiology ; Male ; *Mesothelioma/etiology/mortality ; *Pleural Neoplasms/etiology/mortality ; Sex Factors ; }, } @article {pmid18240400, year = {2007}, author = {Schipperijn, AJ}, title = {[Environmental exposure to asbestos in the area around Goor has been established as the cause of pleural mesothelioma in women].}, journal = {Nederlands tijdschrift voor geneeskunde}, volume = {151}, number = {50}, pages = {2810}, pmid = {18240400}, issn = {0028-2162}, mesh = {Asbestos/*adverse effects ; Environmental Exposure/*adverse effects ; *Household Articles ; Humans ; Lung Neoplasms/*chemically induced ; Mesothelioma/*chemically induced ; }, } @article {pmid18230573, year = {2008}, author = {Margery, J and Ruffié, P}, title = {[Environmental cancer: malignant pleural mesothelioma].}, journal = {Bulletin du cancer}, volume = {95}, number = {1}, pages = {77-86}, doi = {10.1684/bdc.2008.0566}, pmid = {18230573}, issn = {1769-6917}, mesh = {Antineoplastic Agents/therapeutic use ; Asbestos/toxicity ; Biomarkers, Tumor/analysis ; Combined Modality Therapy/methods ; Humans ; Immunotherapy/methods ; *Mesothelioma/diagnosis/etiology/therapy ; Neoplasm Staging ; *Pleural Neoplasms/diagnosis/etiology/therapy ; Prognosis ; Radiotherapy Dosage ; }, abstract = {Malignant pleural mesothelioma (MPM) remains an aggressive tumour, but medical interest has recently evolved from almost nihilism to a real interest. Significant advances are observed in the pathologic diagnosis, the staging, the knowledge of the mesothelial carcinogenesis, the identification of biological markers with potential interest in diagnosis or in treatment. Proper management implies the participation of the general population since the implementation of administrative procedures for social and economical compensation. Active and multidisciplinary therapeutic strategies are currently evaluated and the concept of multimodality treatment includes new effective chemotherapies improving survival and quality of life, modern modalities of radiotherapy and pleuropneumonectomy. This advances create hopes and interrogations because it is not currently know whether multimodality treatment will be the standard in MPM.}, } @article {pmid18227828, year = {2008}, author = {Fennell, DA and Gaudino, G and O'Byrne, KJ and Mutti, L and van Meerbeeck, J}, title = {Advances in the systemic therapy of malignant pleural mesothelioma.}, journal = {Nature clinical practice. Oncology}, volume = {5}, number = {3}, pages = {136-147}, doi = {10.1038/ncponc1039}, pmid = {18227828}, issn = {1743-4262}, mesh = {Antineoplastic Agents/*therapeutic use ; Biomarkers, Tumor ; Combined Modality Therapy ; Folic Acid Antagonists/therapeutic use ; Gene Expression Profiling ; Humans ; Mesothelioma/*drug therapy/genetics/pathology ; Platinum Compounds/therapeutic use ; Pleural Neoplasms/*drug therapy/genetics/pathology ; Positron-Emission Tomography ; Prognosis ; Treatment Outcome ; }, abstract = {Malignant pleural mesothelioma is an aggressive thoracic malignancy associated with exposure to asbestos, and its incidence is anticipated to increase during the first half of this century. Chemotherapy is the mainstay of treatment, yet sufficiently robust evidence to substantiate the current standard of care has emerged only in the past 5 years. This Review summarizes the evidence supporting the clinical activity of chemotherapy, discusses the use of end points for its assessment and examines the influence of clinical and biochemical prognostic factors on the natural history of malignant pleural mesothelioma. Early-phase clinical trials of second-line and novel agents are emerging from an increased understanding of mesothelioma cell biology. Coupled with high-quality translational research, such developments have real potential to improve the outlook of patients at a time of increasing incidence.}, } @article {pmid18218073, year = {2008}, author = {Miserocchi, G and Sancini, G and Mantegazza, F and Chiappino, G}, title = {Translocation pathways for inhaled asbestos fibers.}, journal = {Environmental health : a global access science source}, volume = {7}, number = {}, pages = {4}, pmid = {18218073}, issn = {1476-069X}, mesh = {Asbestos/*pharmacokinetics/toxicity ; Asbestosis/*etiology/pathology ; Biological Transport/physiology ; Extracellular Space/metabolism ; Humans ; Lung/*metabolism ; Lymphatic System/metabolism ; Mineral Fibers/toxicity ; Permeability ; Pleura/*metabolism ; Time Factors ; }, abstract = {We discuss the translocation of inhaled asbestos fibers based on pulmonary and pleuro-pulmonary interstitial fluid dynamics. Fibers can pass the alveolar barrier and reach the lung interstitium via the paracellular route down a mass water flow due to combined osmotic (active Na+ absorption) and hydraulic (interstitial pressure is subatmospheric) pressure gradient. Fibers can be dragged from the lung interstitium by pulmonary lymph flow (primary translocation) wherefrom they can reach the blood stream and subsequently distribute to the whole body (secondary translocation). Primary translocation across the visceral pleura and towards pulmonary capillaries may also occur if the asbestos-induced lung inflammation increases pulmonary interstitial pressure so as to reverse the trans-mesothelial and trans-endothelial pressure gradients. Secondary translocation to the pleural space may occur via the physiological route of pleural fluid formation across the parietal pleura; fibers accumulation in parietal pleura stomata (black spots) reflects the role of parietal lymphatics in draining pleural fluid. Asbestos fibers are found in all organs of subjects either occupationally exposed or not exposed to asbestos. Fibers concentration correlates with specific conditions of interstitial fluid dynamics, in line with the notion that in all organs microvascular filtration occurs from capillaries to the extravascular spaces. Concentration is high in the kidney (reflecting high perfusion pressure and flow) and in the liver (reflecting high microvascular permeability) while it is relatively low in the brain (due to low permeability of blood-brain barrier). Ultrafine fibers (length < 5 mum, diameter < 0.25 mum) can travel larger distances due to low steric hindrance (in mesothelioma about 90% of fibers are ultrafine). Fibers translocation is a slow process developing over decades of life: it is aided by high biopersistence, by inflammation-induced increase in permeability, by low steric hindrance and by fibers motion pattern at low Reynolds numbers; it is hindered by fibrosis that increases interstitial flow resistances.}, } @article {pmid18210075, year = {2008}, author = {Müller, M and Stöckle, M and Pecqueux, JC and Härle, M and Sybrecht, GW and Stichnoth, F and Buchter, A}, title = {[Coincident manifestation of mesotheliomas of the tunica vaginalis and pleura. Case report and literature overview].}, journal = {Der Urologe. Ausg. A}, volume = {47}, number = {2}, pages = {200-204}, pmid = {18210075}, issn = {1433-0563}, mesh = {Aged ; Diagnosis, Differential ; Humans ; Male ; Mesothelioma/*diagnosis/*therapy ; Neoplasms, Multiple Primary/*diagnosis/*therapy ; Pleural Neoplasms/*diagnosis/*therapy ; Testicular Neoplasms/*diagnosis/*therapy ; }, abstract = {Malignant mesotheliomas are rare entities (0.1-0.2% of all malignant tumors) possibly localized at the pleura, peritoneum, pericardium, and tunica vaginalis. Most malignant mesotheliomas are caused by asbestos inhalation. We report on a man who suffered from malignant mesotheliomas of the tunica vaginalis and of the pleura simultaneously. The development of these tumors was probably multicentric; the patient had been exposed to asbestos over a period of 22 years. We discuss the individual findings and the current literature.}, } @article {pmid18209049, year = {2008}, author = {Currie, AJ and van der Most, RG and Broomfield, SA and Prosser, AC and Tovey, MG and Robinson, BW}, title = {Targeting the effector site with IFN-alphabeta-inducing TLR ligands reactivates tumor-resident CD8 T cell responses to eradicate established solid tumors.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {180}, number = {3}, pages = {1535-1544}, doi = {10.4049/jimmunol.180.3.1535}, pmid = {18209049}, issn = {0022-1767}, mesh = {Animals ; Antiviral Agents/pharmacology ; CD8-Positive T-Lymphocytes/*immunology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; *Immunity, Innate/drug effects ; Interferon-alpha/*metabolism ; Interferon-beta/*metabolism ; Ligands ; Lymphocyte Depletion ; Mesothelioma/*immunology ; Mice ; Mice, Inbred BALB C ; Nucleic Acids/immunology ; Poly I-C/pharmacology ; RNA, Double-Stranded/pharmacology ; }, abstract = {Effective antitumor CD8 T cell responses may be activated by directly targeting the innate immune system within tumors. We investigated this response by injecting a range of TLR agonists into established tumors using a mouse model of malignant mesothelioma stably transduced with the hemagglutinin (HA) gene as a marker Ag (AB1-HA). Persistent delivery of the dsRNA mimetic poly(I:C) into established AB1-HA tumors resulted in complete tumor resolution in 40% of mice, with the remaining mice also showing a significant delay in tumor progression. Experiments in athymic nude mice along with CD8 depletion and IFN-alphabeta blocking studies revealed that tumor resolution required both CD8 T cells and type I IFN induction, and was associated with local changes in MHC class I expression. Surprisingly, however, tumor resolution was not associated with systemic dissemination or tumor infiltration of effector CD8 T cells. Instead, the antitumor response was critically dependent on the reactivation of tumor-resident CD8 T cell responses. These studies suggest that, once reactivated, pre-existing local CD8 T cell responses are sufficient to resolve established tumors and that in situ type I IFN is a determining factor.}, } @article {pmid18207296, year = {2008}, author = {Wilson, R and McConnell, EE and Ross, M and Axten, CW and Nolan, RP}, title = {Risk assessment due to environmental exposures to fibrous particulates associated with taconite ore.}, journal = {Regulatory toxicology and pharmacology : RTP}, volume = {52}, number = {1 Suppl}, pages = {S232-45}, doi = {10.1016/j.yrtph.2007.11.005}, pmid = {18207296}, issn = {1096-0295}, mesh = {Air/analysis ; Air Pollutants, Occupational/*adverse effects/analysis ; Asbestosis/epidemiology/*etiology ; Dose-Response Relationship, Drug ; Environmental Exposure/*adverse effects/analysis ; Environmental Monitoring ; Epidemiological Monitoring ; Humans ; Inhalation Exposure ; Iron/*adverse effects/analysis/classification ; Mineral Fibers/adverse effects/analysis/classification ; *Mining ; Minnesota/epidemiology ; Models, Biological ; Odds Ratio ; Particulate Matter/*adverse effects/analysis ; Risk Assessment ; Silicates/*adverse effects/analysis/classification ; }, abstract = {In the early 1970s, it became a concern that exposure to the mineral fibers associated taconite ore processed in Silver Bay, Minnesota would cause asbestos-related disease including gastrointestinal cancer. At that time data gaps existed which have now been significantly reduced by further research. To further our understanding of the types of airborne fibers in Silver Bay we undertook a geological survey of their source the Peter Mitchell Pit, and found that there are no primary asbestos minerals at a detectable level. However we identified two non-asbestos types of fibrous minerals in very limited geological locales. Air sampling useful for risk assessment was done to determine the type, concentrations and size distribution of the population of airborne fibers around Silver Bay. Approximately 80% of the airborne fibers have elemental compositions consistent with cummingtonite-grunerite and the remaining 20% have elemental compositions in the tremolite-actinolite series. The mean airborne concentration of both fiber types is less than 0.00014 fibers per milliliter that is within the background level reported by the World Health Organization. We calculate the risk of asbestos-related mesothelioma and lung cancer using a variety of different pessimistic assumptions. (i) that all the non-asbestos fibers are as potent as asbestos fibers used in the EPA-IRIS listing for asbestos; with a calculated risk of asbestos-related cancer for environmental exposure at Silver Bay of 1 excess cancer in 28,500 lifetimes (or 35 excess cancers per 1,000,000 lifetimes) and secondly that taconite associated fibers are as potent as chrysotile the least potent form of asbestos. The calculated risk is less than 0.77 excess cancer case in 1,000,000 lifetimes. Finally, we briefly review the epidemiology studies of grunerite asbestos (amosite) focusing on the exposure conditions associated with increased risk of human mesothelioma.}, } @article {pmid18206605, year = {2008}, author = {Guha, K and Jones, D and Hull, JH and Ho, TB}, title = {Recurrent hydropneumothorax as a presenting feature of malignant mesothelioma.}, journal = {European journal of internal medicine}, volume = {19}, number = {1}, pages = {63-64}, doi = {10.1016/j.ejim.2007.03.010}, pmid = {18206605}, issn = {1879-0828}, mesh = {Aged ; Asbestos/toxicity ; Diagnosis, Differential ; Humans ; Hydropneumothorax/*diagnosis/etiology/*prevention & control ; Male ; Mesothelioma/*diagnosis/etiology ; Occupational Exposure ; Pleural Neoplasms/*diagnosis/etiology ; Recurrence ; Thoracic Surgery, Video-Assisted ; Tomography, X-Ray Computed ; }, abstract = {A 73-year-old former smoker with previous occupational exposure to asbestos presented with a pneumothorax that was initially managed by simple aspiration. Despite this, it re-accumulated and a bronchopleural fistula was suspected. A video-assisted thoracoscopic procedure was performed and revealed an abnormally thickened pleura that turned out to be a mesothelioma. All persistent pneumothoraces should be investigated.}, } @article {pmid18202164, year = {2008}, author = {Chapman, A and Mulrennan, S and Ladd, B and Muers, MF}, title = {Population based epidemiology and prognosis of mesothelioma in Leeds, UK.}, journal = {Thorax}, volume = {63}, number = {5}, pages = {435-439}, doi = {10.1136/thx.2007.081430}, pmid = {18202164}, issn = {1468-3296}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Asbestos/adverse effects ; England/epidemiology ; Epidemiologic Methods ; Female ; Humans ; Male ; Mesothelioma/drug therapy/*mortality/radiotherapy ; Middle Aged ; Pleural Neoplasms/drug therapy/*mortality/radiotherapy ; Prognosis ; Randomized Controlled Trials as Topic ; }, abstract = {INTRODUCTION: Malignant mesothelioma is a fatal neoplasm, which is rapidly increasing in incidence throughout Western Europe. To date there have been no studies reporting on the natural history and interventional practices on a comprehensive unselected population, as opposed to reports from referral institutions or compensation claimants. We present a population based study capturing data on all patients with mesothelioma presenting within a defined geographical area over a 4 year period in the UK.

METHOD: Data of all cases occurring in Leeds with a population of 750 000 were collected retrospectively from 2002 to 2003 and prospectively from 2004 to 2005. All patients' hospital records and the Trust histology database were reviewed, as well as coroner's reports on all patients with a post mortem diagnosis of mesothelioma.

RESULTS: Over the 4 year study period, there were a total of 146 cases in Leeds; 77% were male. Median age was 74 years (range 36-93). Median survival from diagnosis was 8.9 months. 92% and 8% had histological or cytological confirmation, respectively. 85% had documented evidence of definite or probable exposure to asbestos. 110/146 (75%) had symptomatic pleural effusions at presentation. Twice the number of patients (42 vs 17) were managed with surgical rather than bedside pleurodesis and these had a lower recurrence rate (14% vs 47%; p = 0.02). 122 patients had video assisted thoracoscopic surgery/cutting CT biopsies or chest drains. 73/122 (60%) had prophylactic radiotherapy to these sites. There were seven cases (5%) of tract invasion by tumour and six of these had received prophylactic radiotherapy. Median time to seeding was 174 days. 92/146 (63%) had a performance status of 2 or better at diagnosis but only 54/146 were considered fit for chemotherapy. Of these, 28 (52%) declined chemotherapy; the overall uptake of chemotherapy or entry into a trial was 18%. No patient had radical surgery.

CONCLUSION: This comprehensive population based audit has shown that the median age at presentation of malignant mesothelioma is increasing and baseline performance status and survival is worse than in selected series. 37% of patients were considered suitable for palliative chemotherapy but less than 20% accepted this offer. Thorascopic pleurodesis appears to be associated with fewer recurrences. The role of prophylactic radiotherapy to chest drain and biopsy sites needs reappraisal.}, } @article {pmid18199721, year = {2008}, author = {Amati, M and Tomasetti, M and Scartozzi, M and Mariotti, L and Alleva, R and Pignotti, E and Borghi, B and Valentino, M and Governa, M and Neuzil, J and Santarelli, L}, title = {Profiling tumor-associated markers for early detection of malignant mesothelioma: an epidemiologic study.}, journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology}, volume = {17}, number = {1}, pages = {163-170}, doi = {10.1158/1055-9965.EPI-07-0607}, pmid = {18199721}, issn = {1055-9965}, mesh = {8-Hydroxy-2'-Deoxyguanosine ; Aged ; Angiogenesis Inducing Agents/blood ; Asbestosis/*blood/pathology ; Biomarkers, Tumor/*blood ; Case-Control Studies ; Deoxyguanosine/analogs & derivatives/analysis ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Leukocytes/chemistry ; Male ; Matrix Metalloproteinase 2/blood ; Matrix Metalloproteinase 9/blood ; Mesothelioma/*blood/pathology ; Middle Aged ; Oligonucleotide Array Sequence Analysis ; ROC Curve ; Sensitivity and Specificity ; Tissue Inhibitor of Metalloproteinase-1/blood ; Tissue Inhibitor of Metalloproteinase-2/blood ; }, abstract = {Improved detection methods for diagnosis of asymptomatic malignant mesothelioma (MM) are essential for an early and reliable detection and treatment of this type of neoplastic disease. Thus, focus has been on finding tumor markers in the blood that can be used for noninvasive detection of MM. Ninety-four asbestos-exposed subjects defined at high risk, 22 patients with MM, and 54 healthy subjects were recruited for evaluation of the clinical significance of 8-hydroxy-2'-deoxyguanosine (8OHdG) in WBCs and plasma concentrations of soluble mesothelin-related peptides (SMRPs), angiogenic factors [platelet-derived growth factor beta, hepatocyte growth factor, basic fibroblast growth factor, and vascular endothelial growth factor beta (VEGFbeta)], and matrix proteases [matrix metalloproteinase (MMP) 2, MMP9, tissue inhibitor of metalloproteinase (TIMP) 1, and TIMP2] for potential early detection of MM. The area under receiver operating characteristic (ROC) curves indicate that 8OHdG levels can discriminate asbestos-exposed subjects from healthy controls but not from MM patients. Significant area under ROC curve values were found for SMRPs, discriminating asbestos-exposed subjects from MM patients but not from healthy controls. Except for platelet-derived growth factor beta, the hepatocyte growth factor, basic fibroblast growth factor, and VEGFbeta can significantly differentiate high-risk individuals from healthy control and cancer groups. No diagnostic value was observed for MMP2, MMP9, TIMP1, and TIMP2. In addition to the diagnostic performance defined by the ROC analysis, the sensitivity and specificity results of markers with clinical significance were calculated at defined cutoffs. The combination of 8OHdG, VEGFbeta, and SMRPs best distinguished the individual groups, suggesting a potential indicator of early and advanced MM cancers. The combination of blood biomarkers and radiographic findings could be used to stratify the risk of mesothelioma in asbestos-exposed populations.}, } @article {pmid18197921, year = {2008}, author = {Metintas, M and Metintas, S and Ak, G and Erginel, S and Alatas, F and Kurt, E and Ucgun, I and Yildirim, H}, title = {Epidemiology of pleural mesothelioma in a population with non-occupational asbestos exposure.}, journal = {Respirology (Carlton, Vic.)}, volume = {13}, number = {1}, pages = {117-121}, doi = {10.1111/j.1440-1843.2007.01187.x}, pmid = {18197921}, issn = {1440-1843}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Carcinogens/*toxicity ; Catchment Area, Health ; Environmental Exposure/*adverse effects ; Female ; Humans ; Male ; Mesothelioma/*epidemiology/pathology ; Middle Aged ; Pleural Neoplasms/*epidemiology/pathology ; Prospective Studies ; *Rural Health ; Turkey ; }, abstract = {BACKGROUND AND OBJECTIVE: This study describes the epidemiology of malignant pleural mesothelioma (MPM) in a rural population with environmental asbestos exposure.

METHODS: Patients with diagnosed MPM were recruited and their relevant demographic and exposure data were analysed.

RESULTS: A total of 131 patients with MPM (59 men, 72 women) were studied. The patients' mean age was 57.8 years and the mean exposure duration was 28.9 years. The cumulative fibre count of the villagers ranged from 0.19 to 14.61 fibre/mL-years. Of the 131 patients, 85 had epithelial cell type, 20 had mixed, and eight had sarcomatous pleural mesothelioma. No significant relationship was found between asbestos fibre type and age, exposure period, or cellular type of MPM; similarly, no significant relationship could be found between the cellular type and age or exposure period. Patients with sarcomatous mesotheliomas were considerably older. Only five of 131 (3.8%) patients had a family history of mesothelioma.

CONCLUSIONS: Environmental exposure to asbestos begins at birth and this may be important in the age of disease onset, if a threshold model for cancer initiation is operative. Both men and women had an excess risk of mesothelioma. Given that a family history of MPM was not common in this relatively homogenous patient group, a genetic predisposition to mesothelioma appears unlikely.}, } @article {pmid18194828, year = {2008}, author = {Price, B}, title = {Rapporteur's Report Session 5: assessment of health risk associated with exposure to non-asbestiform amphiboles including ingestion studies.}, journal = {Regulatory toxicology and pharmacology : RTP}, volume = {52}, number = {1 Suppl}, pages = {S204-6}, doi = {10.1016/j.yrtph.2007.11.011}, pmid = {18194828}, issn = {1096-0295}, mesh = {Administration, Oral ; Animals ; Asbestos, Amphibole/*toxicity ; Carcinogenicity Tests ; Carcinogens, Environmental/*toxicity ; Cells, Cultured ; *Disease Models, Animal ; Gastrointestinal Neoplasms/*etiology ; Humans ; Inhalation Exposure ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Mineral Fibers/toxicity ; Organ Culture Techniques ; Risk Assessment ; }, } @article {pmid18187182, year = {2008}, author = {Roggli, VL and Vollmer, RT}, title = {Twenty-five years of fiber analysis: what have we learned?.}, journal = {Human pathology}, volume = {39}, number = {3}, pages = {307-315}, doi = {10.1016/j.humpath.2007.07.005}, pmid = {18187182}, issn = {0046-8177}, mesh = {Adult ; Aged ; Aged, 80 and over ; Animals ; Asbestos/adverse effects/*analysis ; *Asbestosis/epidemiology ; Female ; Humans ; Lung/*chemistry ; Male ; Mesothelioma/chemistry/epidemiology/etiology ; Middle Aged ; Mineral Fibers/adverse effects/analysis ; Occupational Exposure/adverse effects ; Peritoneal Neoplasms/chemistry/epidemiology/etiology ; Pleural Neoplasms/chemistry/epidemiology/etiology ; }, abstract = {Asbestos exposure has resulted in a variety of diseases, including asbestosis, carcinoma of the lung (LC), pleural plaques, and malignant mesothelioma (MM). We hypothesized that there have been significant changes in the mineral fiber content of lung tissue from individuals with these diseases over the past 25 years. Asbestos content was measured in lung tissue samples from 819 individuals using light microscopy (to measure asbestos body concentrations) and scanning electron microscopy (to measure types and concentrations of mineral fibers). Cases were divided chronologically according to those occurring in the first half (group 1) versus those occurring in the second half (group 2). The study included 419 cases of MM, 206 cases of asbestosis, and 340 cases of LC. The median asbestos body count (in asbestos bodies per gram) decreased from group 1 to group 2 for each disease: MM, 480 to 350; asbestosis, 24700 to 19200; and LC, 1600 to 174 (reference range, 0-20). A similar trend was observed for fiber counts by scanning electron microscopy. Amosite was the most frequently detected asbestos fiber type and decreased in frequency of detection and median concentration from group 1 to group 2. Crocidolite showed an increased detection frequency from group 1 to group 2 across all 3 disease categories. The decrease in asbestos body and amosite concentrations over time is consistent with the banning of asbestos from insulation products in 1972. The source for the increased detection of crocidolite was not identified and needs further investigation.}, } @article {pmid18184628, year = {2007}, author = {Reinstein, L}, title = {Examination of the health effects of asbestos and methods of mitigating such impacts: testimony at a U.S. Senate hearing.}, journal = {New solutions : a journal of environmental and occupational health policy : NS}, volume = {17}, number = {4}, pages = {377-379}, doi = {10.2190/NS.17.4.k}, pmid = {18184628}, issn = {1048-2911}, mesh = {Air Pollutants/*adverse effects ; Asbestos/*adverse effects ; Environmental Exposure/*adverse effects ; Government ; Humans ; Inhalation Exposure/adverse effects ; Mesothelioma/*chemically induced/epidemiology ; *Politics ; United States ; }, } @article {pmid18171598, year = {2008}, author = {Constantopoulos, SH}, title = {Environmental mesothelioma associated with tremolite asbestos: lessons from the experiences of Turkey, Greece, Corsica, New Caledonia and Cyprus.}, journal = {Regulatory toxicology and pharmacology : RTP}, volume = {52}, number = {1 Suppl}, pages = {S110-5}, doi = {10.1016/j.yrtph.2007.11.001}, pmid = {18171598}, issn = {1096-0295}, mesh = {Air Pollutants/*adverse effects/analysis ; Asbestos, Amphibole/*adverse effects/analysis ; Asbestosis/diagnosis/epidemiology/*etiology ; Calcinosis/epidemiology/etiology/pathology ; Carcinogens, Environmental/*adverse effects/analysis ; *Disease Outbreaks ; Female ; Humans ; Male ; Mediterranean Region/epidemiology ; Mesothelioma/diagnosis/epidemiology/*etiology ; Mineral Fibers/adverse effects/analysis ; Pleural Diseases/epidemiology/etiology/pathology ; Zeolites/adverse effects/analysis ; }, abstract = {Mediterranean regions such as Greece, Turkey, Cyprus, Corsica and New Caledonia have experienced epidemics of malignant mesothelioma as a result of non-occupational, "domestic" exposure to tremolite asbestos and fibrous erionite. This exposure to tremolite asbestos and fibrous erionite is typified "domestic" due to its prevalence in regions with natural deposits of tremolite asbestos (or fibrous erionite) where the material from tremolite asbestos or fibrous erionite is used for domestic applications such as whitewashing. However, these exposures may be useful in examining the potential consequences of even small amounts of amphibole asbestos fibers in the ambient air. It can also elucidate the effects of fibers that behave like amphibole asbestos. However, this type of exposure is not useful for studying the potential effects of small amounts of asbestos in the ambient air of big cities due to the differing nature of the fiber types and modes of exposure between the regions.}, } @article {pmid18166941, year = {2007}, author = {Margery, J and Ruffié, P}, title = {[Malignant pleural mesothelioma: interrogations and hopes concerning the expected epidemic].}, journal = {Revue de pneumologie clinique}, volume = {63}, number = {6}, pages = {354-364}, doi = {10.1016/s0761-8417(07)78422-5}, pmid = {18166941}, issn = {0761-8417}, mesh = {Asbestos/adverse effects ; Chemotherapy, Adjuvant ; Humans ; Immunization, Passive ; Lung Neoplasms/chemically induced/diagnosis/epidemiology/*therapy ; Mesothelioma/chemically induced/diagnosis/epidemiology/*therapy ; Neoplasm Staging ; Radiotherapy, Adjuvant ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare incurable tumor. Interest in MPM has increased in recent years due to a steadily increasing incidence subsequent to the intensive use of asbestosis, the main causal agent, but also due to better awareness in the political and scientific communities faced with a serious public health issue. Our knowledge of MPM has improved regularly in terms of pathologic diagnosis and the mechanisms underlying the mesothelial carcinogenesis. MPM is also the subject of many technological innovations as illustrated by the recent identification of new biological markers, access to metabolic imaging, and clinical research on targeted treatments. Proper management implies the participation of the general population since the implementation of administrative procedures for social indemnities. In 2007, a more aggressive therapeutic approach is becoming common practice with the use of radiotherapy and the emergence of the concept of multimodal care centered on wide pleuropneumonectomy. These advances create real hope for improvement, but also many interrogations since no standard treatment protocol has been clearly identified.}, } @article {pmid18166940, year = {2007}, author = {Brochard, P}, title = {[Malignant pleural mesothelioma: facts and unresolved questions].}, journal = {Revue de pneumologie clinique}, volume = {63}, number = {6}, pages = {349-351}, doi = {10.1016/s0761-8417(07)78421-3}, pmid = {18166940}, issn = {0761-8417}, mesh = {Asbestos/adverse effects ; Environmental Exposure/adverse effects ; Genetic Predisposition to Disease ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Mineral Fibers/adverse effects ; Pedigree ; }, } @article {pmid19621651, year = {2008}, author = {Szeszenia-Dabrowska, N}, title = {[Asbestos as a risk factor for pulmonary diseases].}, journal = {Przeglad lekarski}, volume = {65 Suppl 2}, number = {}, pages = {26-34}, pmid = {19621651}, issn = {0033-2240}, mesh = {Adolescent ; Adult ; Aged ; Asbestos/*adverse effects ; Child ; Child, Preschool ; Environmental Exposure/prevention & control ; Female ; Humans ; Incidence ; Infant ; Male ; Middle Aged ; Occupational Exposure/legislation & jurisprudence/*prevention & control ; Poland/epidemiology ; Respiratory Tract Diseases/diagnosis/*epidemiology/etiology ; Risk Factors ; Survival Rate ; Young Adult ; }, abstract = {Asbestos is a recognised carcinogen, one of the most dangerous pollutants in the human environment. This is associated with a huge accumulation of asbestos-containing materials that, as a result of their degradation, release fibres that are practically indestructible. It is estimated that in recent years, asbestos was responsible for ca. 100 thousand death cases p.a. The pathogenic effects of asbestos on the respiratory system (the target organ) result from the inhalation of the respirable asbestos fibres suspended in the ambient air. The fibres accumulate in the lung tissue during the whole human lifetime, and the pathogenic effects become evident after a long period of latency, ranging from 20 to 40 years. A specific feature of asbestos activity is that the pathologies appear even after cessation of the exposure; another feature is the development of mesotheliomas associated with the environmental exposure. In Poland, the Act of 1997 banning the use of asbestos products has solved the problems associated with the occupational exposure in the asbestos processing industry, and prevented further accumulation of asbestos products. However, problems of the environmental exposures to asbestos remain unsolved. In spite that no worker has been occupationally exposed to asbestos during the recent 10 years, new cases of asbestosis, lung cancer pleural mesothelioma, non-malignant pleural diseases continue to be detected each year among the former workers of asbestos processing industry ("Amiantus" project). This paper reports on the current status of asbestos-related diseases in Poland and worldwide, risk of the development of lung cancers and asbestos-specific mesotheliomas and gives recent recommendations for diagnosing and certification of asbestos-related diseases.}, } @article {pmid18154821, year = {2008}, author = {Pass, HI and Wali, A and Tang, N and Ivanova, A and Ivanov, S and Harbut, M and Carbone, M and Allard, J}, title = {Soluble mesothelin-related peptide level elevation in mesothelioma serum and pleural effusions.}, journal = {The Annals of thoracic surgery}, volume = {85}, number = {1}, pages = {265-72; discussion 272}, doi = {10.1016/j.athoracsur.2007.07.042}, pmid = {18154821}, issn = {1552-6259}, mesh = {Adult ; Aged ; Aged, 80 and over ; Analysis of Variance ; Area Under Curve ; Asbestosis/blood/complications/mortality/pathology ; Biomarkers, Tumor/*blood ; Case-Control Studies ; Female ; GPI-Linked Proteins ; Humans ; Immunohistochemistry ; Male ; Membrane Glycoproteins/*blood ; Mesothelin ; Mesothelioma/*blood/complications/mortality/pathology ; Middle Aged ; Neoplasm Staging ; Pleural Effusion, Malignant/*blood/etiology ; Pleural Neoplasms/*blood/complications/mortality/pathology ; Prognosis ; ROC Curve ; Retrospective Studies ; Risk Assessment ; Sensitivity and Specificity ; Survival Analysis ; }, abstract = {BACKGROUND: Soluble mesothelin-related peptide (SMRP) is a potential marker for malignant pleural mesothelioma (MPM), which may be useful for screening high-risk asbestos-exposed individuals.

METHODS: We evaluated SMRP in serum from MPM patients (n = 90), lung cancer patients (n = 170), age and tobacco-matched asbestos-exposed individuals (n = 66), and in MPM pleural effusions (n = 45), benign effusions (n = 30), and non-MPM effusions (n = 20) using the MesoMark enzyme-linked immunosorbent assay kit (Fujirebio Diagnostics, Malvern, PA). Receiver operating characteristic (ROC) curves were used to define true and false positive rates at various cutoffs.

RESULTS: Mean serum SMRP levels were higher in MPM compared with lung cancer (5.67 +/- 0.82 nM [mean +/- standard error of the mean vs 1.99 +/- 0.43 nM, p < 0.001), and stage I MPM SMRP levels (n = 12; 2.09 +/- 0.41 nM) were significantly higher than those in asbestos-exposed individuals (0.99 +/- 0.09 nM, p = 0.02, respectively). Stage 2 to 4 SMRP serum levels were significantly higher than those for stage 1 MPM. The area under the ROC curve for serum SMRP was 0.81 for differentiating MPM and asbestos-exposed individuals; cutoff = 1.9 nM (sensitivity = 60%, specificity = 89%). The MPM pleural effusion SMRP was significantly higher than benign or other non-MPM pleural effusions (65.57 +/- 11.33 nM vs 27.46 +/- 11.25 nM [p = 0.003] and 18.99 +/- 7.48 nM [p = 0.044], respectively).

CONCLUSIONS: These data support SMRP as a promising marker for MPM in both serum and pleural effusion fluid, and justify prospective screening studies of SMRP in combination with other markers for screening of asbestos-exposed cohorts.}, } @article {pmid18098288, year = {2008}, author = {Reid, A and Heyworth, J and de Klerk, NH and Musk, B}, title = {Cancer incidence among women and girls environmentally and occupationally exposed to blue asbestos at Wittenoom, Western Australia.}, journal = {International journal of cancer}, volume = {122}, number = {10}, pages = {2337-2344}, doi = {10.1002/ijc.23331}, pmid = {18098288}, issn = {1097-0215}, mesh = {Adenocarcinoma/epidemiology ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asbestos, Crocidolite/*pharmacology ; Case-Control Studies ; Child ; Cohort Studies ; *Environmental Exposure ; Female ; Humans ; Incidence ; Lung Neoplasms/*epidemiology ; Mesothelioma/*epidemiology ; Middle Aged ; Mining ; *Occupational Exposure ; Surveys and Questionnaires ; Western Australia/epidemiology ; }, abstract = {The impact of crocidolite exposure on the health of former Wittenoom miners and millers (largely male) has been well documented. Less is known about the health outcomes of the 2,968 women and girls who lived (N = 2,552) and worked (N = 416) in the blue asbestos milling and mining town of Wittenoom between 1943 and 1992. Quantitative exposure measurements were derived from dust studies undertaken over the lifetime of the mine and mill and the township. Incident cancers were obtained from the Western Australian (WA) Cancer Registry and the National Cancer Clearing House. Standardized incidence ratios (SIRS) compared Wittenoom females with the WA female population. Exposure-response relationships were examined using a matched case-control study design. There were (47) mesothelioma and (55) lung cancer cases among the 437 cancers in the Wittenoom females over the period 1960-2005. When compared to the WA female population, Wittenoom women and girls had higher rates of mesothelioma and possibly lung cancer. Mesothelioma incidence rates are increasing with the incidence rate of 193 per 100,000 in the period 2000-2005 being more than double that for the period 1995-1999 at 84 per 100,000. A significant exposure-response relationship was present for mesothelioma, but not for lung cancer. Forty years after the asbestos mine and mill at Wittenoom were closed, there is a high toll from cancer among the former female residents of the town and company workers.}, } @article {pmid18095999, year = {2008}, author = {Barresi, V and Vitarelli, E and Barresi, G}, title = {Acne inversa complicated by squamous cell carcinoma in association with diffuse malignant peritoneal mesothelioma arising in the absence of predisposing factors: a case report.}, journal = {Journal of cutaneous pathology}, volume = {35}, number = {1}, pages = {70-73}, doi = {10.1111/j.1600-0560.2007.00766.x}, pmid = {18095999}, issn = {1600-0560}, mesh = {Carcinoma, Squamous Cell/complications/*pathology/surgery ; Fatal Outcome ; Hidradenitis Suppurativa/complications/*pathology ; Humans ; Male ; Mesothelioma/complications/*pathology/surgery ; Middle Aged ; Skin Neoplasms/complications/*pathology/surgery ; }, abstract = {Diffuse malignant peritoneal mesothelioma (DMPM) is a relatively rare neoplasm. Risk factors associated with its development include asbestos exposure, chronic irritation or inflammation of the peritoneum, abdominal radiotherapy, familial Mediterranean fever and simian virus 40. A familial segregation of this neoplasia has been reported in small villages of the Cappadocian region of Turkey, and it has been postulated that hereditary factors may predispose to mesothelioma, even with exposure to small amounts of asbestos. We report a case of DMPM, which apparently occurred in the absence of predisposing factors in a patient with a clinical history characterized by recurrent pre-sacral acne inversa of long duration. The association of this chronic inflammatory disease with DMPM has never been reported. The genetic locus for acne inversa has recently been identified within the 1p21.1-1q25.3 chromosomal region. Interestingly, frequent losses in chromosomal region 1p.21-22 have been found in mesothelioma as well. It is thus tempting to speculate that genetic mutations involving chromosome 1p.21-22 may account for the development of both diseases.}, } @article {pmid18094988, year = {2008}, author = {Marinaccio, A and Scarselli, A and Binazzi, A and Altavista, P and Belli, S and Mastrantonio, M and Pasetto, R and Uccelli, R and Comba, P}, title = {Asbestos related diseases in Italy: an integrated approach to identify unexpected professional or environmental exposure risks at municipal level.}, journal = {International archives of occupational and environmental health}, volume = {81}, number = {8}, pages = {993-1001}, pmid = {18094988}, issn = {1432-1246}, mesh = {Asbestos/*poisoning ; Cluster Analysis ; Environmental Exposure/adverse effects/*analysis ; Female ; Humans ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology/etiology/mortality ; Occupational Exposure/adverse effects/*analysis ; Pleural Neoplasms/*epidemiology/etiology/mortality ; Research Design ; Risk Assessment ; }, abstract = {PURPOSE: Past intensive use of asbestos has implied severe public health consequences. Spatial distribution of deaths from malignant mesothelioma and of compensated cases for asbestos related diseases in Italy were compared to identify unexpected sources of asbestos exposure.

METHODS: Mortality for malignant mesothelioma at municipal level and geographical clusters of compensated cases for asbestos related diseases, as proxy of industrial asbestos exposure, were identified in the period 1988-2001.

RESULTS: Municipalities with at least four mesothelioma deaths and a statistically significant mortality excess were 148; and 53 out of them had no compensated case for asbestos-related diseases. Finally 22 of these lay outside of any aforementioned cluster, thus suggestive of a possible unrecognized exposure.

CONCLUSIONS: Availability long-term national figures and the different etiology of asbestos related diseases are the key features of this exercise that was applied to Italy, but can be replicated wherever registration systems of diseases related to long term exposure to asbestos are available.}, } @article {pmid18086752, year = {2008}, author = {Kothmaier, H and Quehenberger, F and Halbwedl, I and Morbini, P and Demirag, F and Zeren, H and Comin, CE and Murer, B and Cagle, PT and Attanoos, R and Gibbs, AR and Galateau-Salle, F and Popper, HH}, title = {EGFR and PDGFR differentially promote growth in malignant epithelioid mesothelioma of short and long term survivors.}, journal = {Thorax}, volume = {63}, number = {4}, pages = {345-351}, doi = {10.1136/thx.2007.085241}, pmid = {18086752}, issn = {1468-3296}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*metabolism ; Cell Communication ; Cell Proliferation ; ErbB Receptors/*metabolism ; Female ; Humans ; Immunohistochemistry ; Male ; Mesothelioma/mortality/*pathology ; Microarray Analysis ; Middle Aged ; Neoplasm Proteins/*metabolism ; Pleural Neoplasms/mortality/*pathology ; Prognosis ; Receptors, Platelet-Derived Growth Factor/*metabolism ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is an asbestos related tumour difficult to detect early and treat effectively. Asbestos causes genetic modifications and cell signalling events that favour the resistance of MPM to apoptosis and chemotherapy. Only a small number of patients, approximately 10%, survive more than 3 years. The aim of our study was to assess possible differences within signalling pathways between short term survivors (survival <3 years; STS) and long term survivors (survival >3 years; LTS) of MPM.

METHODS: 37 antibodies detecting proteins engaged in cell signalling pathways, enforcing proliferation, antiapoptosis, angiogenesis and other cellular activities were investigated by tissue microarray (TMA) technology.

RESULTS: Epidermal growth factor receptor (EGFR) was expressed stronger in LTS whereas platelet derived growth factor receptor (PDGFR) signalling was more abundant in STS. Expression of TIE2/Tek, a receptor for tyrosine kinases involved in angiogenesis, was differentially regulated via PDGFR and thus is more important in STS. Antiapoptosis was upregulated in STS by signal transducer and activator of transcription 1 (STAT1)-survivin and related molecules, but not in LTS. Our study provides novel insights into the regulatory mechanisms of signalling pathways in MPM, which differentially promote tumour growth in LTS and STS.

CONCLUSION: We have demonstrated that small scale proteomics can be carried out by powerful linkage of TMA, immunohistochemistry and statistical methods to identify proteins which might be relevant targets for therapeutic intervention.}, } @article {pmid18079154, year = {2008}, author = {Rushton, L and Hutchings, S and Brown, T}, title = {The burden of cancer at work: estimation as the first step to prevention.}, journal = {Occupational and environmental medicine}, volume = {65}, number = {12}, pages = {789-800}, doi = {10.1136/oem.2007.037002}, pmid = {18079154}, issn = {1470-7926}, mesh = {Asbestos/toxicity ; Carcinogens/toxicity ; Female ; Humans ; Lung Neoplasms/etiology/mortality ; Male ; Mesothelioma/etiology/mortality ; Neoplasms/*epidemiology/etiology/prevention & control ; Occupational Diseases/*epidemiology/etiology/prevention & control ; Occupational Exposure/adverse effects/analysis ; Risk Assessment/methods ; United Kingdom/epidemiology ; }, abstract = {OBJECTIVES: Work-related cancers are largely preventable. The overall aim of this project is to estimate the current burden of cancer in Great Britain attributable to occupational factors, and identify carcinogenic agents, industries and occupations for targeting risk prevention.

METHODS: Attributable fractions and numbers were estimated for mortality and incidence for bladder, lung, non-melanoma skin, and sinonasal cancers, leukaemia and mesothelioma for agents and occupations classified as International Agency for Research on Cancer (IARC) Group 1 and 2A carcinogens with "strong" or "suggestive" evidence for carcinogenicity at the specific cancer site in humans. Risk estimates were obtained from published literature and national data sources used for estimating proportions exposed.

RESULTS: In 2004, 78,237 men and 71,666 women died from cancer in Great Britain. Of these, 7317 (4.9%) deaths (men: 6259 (8%); women: 1058 (1.5%)) were estimated to be attributable to work-related carcinogens for the six cancers assessed. Incidence estimates were 13,338 (4.0%) registrations (men: 11,284 (6.7%); women 2054 (1.2%)). Asbestos contributed over half the occupational attributable deaths, followed by silica, diesel engine exhaust, radon, work as a painter, mineral oils in metal workers and in the printing industry, environmental tobacco smoke (non-smokers), work as a welder and dioxins. Occupational exposure to solar radiation, mineral oils and coal tars/pitches contributed 2557, 1867 and 550 skin cancer registrations, respectively. Industries/occupations with large numbers of deaths and/or registrations include construction, metal working, personal and household services, mining (not metals), land transport and services allied to transport, roofing, road repair/construction, printing, farming, the Armed Forces, some other service industry sectors and manufacture of transport equipment, fabricated metal products, machinery, non-ferrous metals and metal products, and chemicals.

CONCLUSIONS: Estimates for all but leukaemia are greater than those currently used in UK health and safety strategy planning and contrast with small numbers (200-240 annually) from occupational accidents. Sources of uncertainty in the estimates arise principally from approximate data and methodological issues. On balance, the estimates are likely to be a conservative estimate of the true risk. Long latency means that past high exposures will continue to give substantial numbers in the near future. Although levels of many exposures have reduced, recent measurements of others, such as wood dust and respirable quartz, show continuing high levels.}, } @article {pmid18078700, year = {2008}, author = {Gamble, J}, title = {Risk of gastrointestinal cancers from inhalation and ingestion of asbestos.}, journal = {Regulatory toxicology and pharmacology : RTP}, volume = {52}, number = {1 Suppl}, pages = {S124-53}, doi = {10.1016/j.yrtph.2007.10.009}, pmid = {18078700}, issn = {1096-0295}, mesh = {Administration, Oral ; Asbestos/administration & dosage/*adverse effects ; Asbestosis/epidemiology/*etiology ; Carcinogens, Environmental/*adverse effects ; *Eating ; Female ; Gastrointestinal Neoplasms/epidemiology/*etiology ; Humans ; *Inhalation Exposure ; Lung Neoplasms/epidemiology/etiology ; MEDLINE ; Male ; Mesothelioma/epidemiology/etiology ; Odds Ratio ; Risk Assessment ; }, abstract = {This paper summarizes the weight of epidemiological evidence to evaluate the hypothesis that asbestos exposure is causally associated with increased risk of gastrointestinal (GI) cancers as suggested by Selikoff in an early study of insulation workers. This review looks at populations that develop GI cancers, namely stomach, colorectal, colon and rectal. Guidelines for assessing causality are strength of association, biological gradient and consistency of the associations. Exposure-response (E-R) was evaluated using three methods to estimate exposure. Rate Ratios (RRs) for lung cancer and percent of mesothelioma are used as surrogate measures of asbestos exposure for all the cohorts of exposed workers. Quantitative or semi-quantitative estimates of cumulative exposure to asbestos were also used to assess E-R trends and were compared to E-R trends for lung cancer and mesothelioma in individual studies. Surrogate measures are important since there are few individual studies that have assessed E-R. None of the various methods to estimate asbestos exposure yielded consistent E-R trends and the strength of the associations were consistently weak or non-existent for the four types of GI cancers. The epidemiological evidence detracts from the hypothesis that occupational asbestos exposure increases the risk of stomach, colorectal, colon, and rectal cancer. Findings are briefly summarized below.}, } @article {pmid18072311, year = {2007}, author = {McCulloch, J and Tweedale, G}, title = {Shooting the messenger: the vilification of Irving J. Selikoff.}, journal = {International journal of health services : planning, administration, evaluation}, volume = {37}, number = {4}, pages = {619-634}, doi = {10.2190/HS.37.4.b}, pmid = {18072311}, issn = {0020-7314}, mesh = {Asbestos/history ; Asbestosis/history ; Extraction and Processing Industry/history ; History, 20th Century ; Humans ; Mesothelioma/chemically induced/history ; Occupational Exposure/adverse effects/history ; United States ; }, abstract = {Dr. Irving J. Selikoff (1915-1992), a New York physician based at Mount Sinai Hospital, was the leading American medical expert on asbestos-related diseases between the 1960s and early 1990s. In a country that had been the world's greatest consumer of asbestos, he was also at the center of the key controversies connected with the mineral. In these controversies, Selikoff was consistently demonized as a media zealot who exaggerated the risks of asbestos on the back of bogus medical qualifications and flawed science. Since his death, the criticism has become even more vituperative and claims have persisted that he was malicious or a medical fraud. However, most of the attacks on Selikoff were inspired by the asbestos industry or its sympathizers, and for much of his career he was the victim of a sustained and orchestrated campaign to discredit him. The most serious criticisms usually more accurately describe his detractors than Selikoff himself.}, } @article {pmid18072089, year = {2008}, author = {Loreto, C and Rapisarda, V and Carnazza, ML and Musumeci, G and Valentino, M and Fenga, C and Martinez, G}, title = {Fluoro-edenite fibres induce lung cell apoptosis: an in vivo study.}, journal = {Histology and histopathology}, volume = {23}, number = {3}, pages = {319-326}, doi = {10.14670/HH-23.319}, pmid = {18072089}, issn = {1699-5848}, mesh = {Animals ; Apoptosis/*drug effects ; Asbestos, Amphibole/pharmacology/toxicity ; Caspase 3/metabolism ; DNA Damage/drug effects ; Environmental Exposure/*adverse effects ; Epithelial Cells/drug effects/metabolism/pathology ; Female ; In Situ Nick-End Labeling ; Lung/*drug effects/metabolism/*pathology ; Mineral Fibers/*toxicity ; Poly(ADP-ribose) Polymerases/metabolism ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Sheep ; Sicily ; bcl-2-Associated X Protein/metabolism ; }, abstract = {We previously showed that apoptosis in the lungs of sheep exposed to fluoro-edenite fibres is induced via the receptor pathway. The present study was performed to gain further insights into the mechanisms of activation of programmed cell death induced by the fibres. Fluoro-edenite fibres are similar in size and morphology to some amphibolic asbestos fibres. They have been found in benmoreitic lavas, in the local stone quarry, in building materials and in road paving at Biancavilla, a town in eastern Sicily (Italy), where epidemiological surveys revealed a cluster of mortality from pleural mesothelioma. Inhalation of asbestos fibres can cause chronic inflammation and carcinogenesis. Since fluoro-edenite has been shown to activate the apoptotic process, we set out to characterise the expression of apoptosis-regulating proteins in fluoro-edenite-exposed lung disease and sought to determine if apoptosis results from fluoro-edenite exposure. Lung tissue from apparently healthy sheep habitually grazing near Biancavilla was processed for immunohistochemical localisation of bcl-2 and bax. Results showed epithelial and interstitial bax overexpression, especially in cells directly in contact with the fibres, and negative bcl-2 immunoexpression. TUNEL-positive cells were detected in alveoli and connective tissue. The integrity of alveolar epithelium and alveolar apoptosis are critical determinants in the pathways that initiate fibrogenesis in the lung and fibroblastic foci are usually found close to abnormal or denuded alveolar epithelium. Our results are consistent with the hypothesis that apoptosis is an important mechanism for removing cells with irreparable fluoro-edenite-induced genetic changes that predispose them to a neoplastic evolution.}, } @article {pmid18064866, year = {2007}, author = {Sinninghe Damsté, HE and Siesling, S and Burdorf, A}, title = {[Environmental exposure to asbestos in the area around Goor has been established as the cause of pleural mesothelioma in women].}, journal = {Nederlands tijdschrift voor geneeskunde}, volume = {151}, number = {44}, pages = {2453-2459}, pmid = {18064866}, issn = {0028-2162}, mesh = {Asbestos/*adverse effects ; Asbestosis/epidemiology ; Carcinogens ; Cluster Analysis ; Environmental Exposure/*adverse effects ; Female ; Humans ; Incidence ; Lung Neoplasms/*chemically induced/epidemiology ; Mesothelioma/*chemically induced/epidemiology ; Netherlands/epidemiology ; Occupational Diseases/chemically induced/epidemiology ; Occupational Exposure/adverse effects ; Registries ; Risk Factors ; }, abstract = {OBJECTIVE: To determine whether a disease cluster of 22 additional cases of pleural mesothelioma among women could be attributed to environmental asbestos exposure due to asbestos fibers from waste material on roads and property yards. The women studied were observed in an area with substantial environmental exposure to asbestos during the period 1989-2002.

DESIGN: Ecological study.

METHOD: In the study period of 1989-2002, all cases of mesothelioma among women, based on a strict histopathologic definition, occurring in the region of Twente, The Netherlands (n = 59) were provided by the regional cancer register. Additional information was collected on the occupational histories of the cases and their partners and addresses of residence through medical records, general practitioners, and next-of-kin. Environmental asbestos exposure was assigned to all cases that had had a long-term stay in a house in the area around Goor with demonstrated local environmental asbestos pollution and where any contact with asbestos through occupation or in the household had been excluded.

RESULTS: In the risk area around Goor, out ofa total of 28 cases ofwomen with pleural mesothelioma, asbestos in the environment was found to be the only source of asbestos exposure for to women. In a further 4 women, environmental asbestos exposure was found to be the most likely cause of pleural mesothelioma. The average cumulative exposure was around 0.11 fiber/ml x exposure years. The observed extra incidence of 22 cases was attributed to the environmental exposure to asbestos in 64% (14/22) of cases.

CONCLUSION: The environmental pollution to asbestos waste materials in the area around Goor was the main cause of the strongly increased incidence of pleural mesothelioma among women in this area. Taking into account an equal risk among men, the consequences of asbestos exposure in the area around Goor in the next 25 years are likely to result in 2 cases of pleural mesothelioma each year.}, } @article {pmid18064858, year = {2007}, author = {van der Laan, G}, title = {[Mesothelioma incidence around Goor, The Netherlands, and far beyond: the asbestos drama unfolds].}, journal = {Nederlands tijdschrift voor geneeskunde}, volume = {151}, number = {44}, pages = {2422-2425}, pmid = {18064858}, issn = {0028-2162}, mesh = {Asbestos/*adverse effects ; Asbestosis/epidemiology ; Carcinogens ; Female ; Humans ; Incidence ; Lung Neoplasms/chemically induced/epidemiology ; Male ; Mesothelioma/*chemically induced/*epidemiology ; Netherlands/epidemiology ; Occupational Diseases/chemically induced/epidemiology ; Occupational Exposure/*adverse effects ; }, abstract = {Whereas the carcinogenic properties of asbestos have been known for more than 70 years, the mesothelioma epidemic in Europe has not yet reached its peak. After occupationally induced cases, environmental cases are being revealed at an ever-increasing rate. In 2005 a total ban on the production and use of asbestos in Europe was announced. Worldwide, the use of asbestos has shifted towards emerging economies such as those occurring in Asia. Economic reasons and a strong lobby from the asbestos industry explain the delay in the implementation of proper preventive actions as well as the global shift. The WHO and the International Labour Office are collaborating towards the elimination of asbestos-related diseases worldwide. More awareness is needed in order to prevent similar tragedies occurring from other side effects of work.}, } @article {pmid18051806, year = {2007}, author = {Sawazaki, H and Yoshikawa, T and Takahashi, T and Taki, Y and Takeuchi, H and Sakai, Y}, title = {[Renal cell carcinoma with malignant pleural mesothelioma after asbestos exposure: a case report].}, journal = {Hinyokika kiyo. Acta urologica Japonica}, volume = {53}, number = {11}, pages = {805-808}, pmid = {18051806}, issn = {0018-1994}, mesh = {Aged ; Asbestos/*adverse effects ; Carcinoma, Renal Cell/diagnosis/*etiology/pathology/therapy ; Combined Modality Therapy ; Humans ; Kidney Neoplasms/diagnosis/*etiology/pathology/therapy ; Male ; Mesothelioma/diagnosis/*etiology/pathology/therapy ; *Neoplasms, Multiple Primary ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/diagnosis/*etiology/pathology/therapy ; }, abstract = {A 66-year-old man visited complaining of cough and sore throat. He had been exposed to asbestos 43 years ago. Chest X-ray revealed left pleural effusion and abnormal shadow in the right lung field. Chest computed tomography (CT) showed multiple enhanced nodules in the right pleural cavity. Abdominal CT showed a 3-cm enhanced tumor in the lower pole of the left kidney. Left radical nephrectomy was performed. Pathological diagnosis was renal cell carcinoma. Postoperatively pleural biopsy was performed by using thoracoscopy. White plaque was seen at the costal pleura and surface of lung. Pathological diagnosis was malignant pleural mesothelioma based on using mesothelium-associated antibodies: calretinin (+), CK5/6 (+), D2-40 (+), HBME-1 (+), TTF-1 (-), MOC31 (-), CEA (-). Combination therapy (extrapleural pneumonectomy, chemotherapy, and radiotherapy) was initiated. Malignant mesothelioma is a devastating neoplasm with a strong etiological relationship with asbestos exposure. The incidence is rising in industrialized countries, with the peak expected in the year 2020. However, renal cell carcinoma with malignant pleural mesothelioma is very rare and this is the 2nd case in the Japanese literature.}, } @article {pmid18050862, year = {2007}, author = {Silvestri, S and Benvenuti, A}, title = {[Asbestos exposure circumstances and malignant mesothelioma casuistry of the Tuscan Registry: preliminary indications on the efficacy of dust control measures introduced during the Seventies].}, journal = {Epidemiologia e prevenzione}, volume = {31}, number = {4 Suppl 1}, pages = {75-80}, pmid = {18050862}, issn = {1120-9763}, mesh = {Asbestos/*adverse effects ; Humans ; Italy ; Lung Neoplasms/*etiology/*prevention & control ; Mesothelioma/*etiology/*prevention & control ; Occupational Diseases/*etiology/*prevention & control ; Occupational Exposure/*adverse effects/*prevention & control ; *Registries ; }, } @article {pmid18050861, year = {2007}, author = {Carnevale, F}, title = {[Asbestos: a long lasting tragedy. Useful considerations for a historical reconstruction of the most remarkable facts].}, journal = {Epidemiologia e prevenzione}, volume = {31}, number = {4 Suppl 1}, pages = {53-74}, pmid = {18050861}, issn = {1120-9763}, mesh = {Asbestos/*adverse effects/*history ; Asbestosis/etiology/*history ; England ; History, 20th Century ; Humans ; Italy ; Lung Neoplasms/etiology/*history ; Mesothelioma/etiology/*history ; Occupational Exposure/adverse effects/legislation & jurisprudence ; }, abstract = {A thought back on the "epic of asbestos" scanning the fundamental steps, from the "discovery" of the adverse effects for the workers. A first phase, the "asbestosis one" concluded in Britain in the early thirties with the issue of a technical legislation is described. It was the first regulation shared by the Unions and the asbestos companies, some of which were or will then become leaders all over the world. The main effect of this legislation enforcement is the reduction of the exposure in some units of the asbestos textile industry; no effects were observed instead in other asbestos industrial divisions where it's consumption for insulations and asbestos cement increased massively. The second phase lasting approximately thirty years next sees together to a formidable diffusion of all the asbestos fibres including the crocidolite ones, advertised and accepted like "indispensable" for the economical and social development, an absolute leadership of the companies in the management of health effects information for the workers and therefore also those on the pulmonary cancerogenicity. Such selfish and aggressive leadership, receives in return from government, labour and consumers organizations just inertia, impotence and incredulity. This attitude will also continue in the third phase, beginning in the early sixties of the last century. The time period will be dominated by mesothelioma with all its new and terrible meanings, the dangerousness of asbestos exposure especially to the blue one even at lower levels than those observed in the past for other pathologies and the long latency before the appearance of the effects. Discussing about asbestos substitutes was out of the agenda, indeed just in the period where the mining and the consumption of asbestos touched the highest levels. The initiatives assumed in some countries like the auto limitation of the use of crocidolite and a more rigorous reduction of the occupational exposures will only turn out useful in order to lower the risk for asbestosis and, probably, the one for pulmonary tumour. In the United States, the judicial litigation for compensation between the workers and the companies begins. The same phenomenon will characterize also in the other countries industrializes the fourth phase of the epic, until our days; it is just in these years, and especially during the eighties, that industry starts thinking about the substitution of asbestos; the lively public debate will favour initiatives oriented to obtain economic compensation for damages caused by past occupational and environmental exposures. These legal actions will carry to bankruptcy all the asbestos companies and later to the ban of asbestos. The judicial debates will also uncover "confidential" information useful to better reconstruct the epic, to formulate more dispassionate historical judgments and to allow everyone on answering to more complex questions and more important than how much generally it was previously believed; all this should happen contextualizing the ages in which the scientific acquaintances on the effects of asbestos have been published and disproving prejudgments, able to affect some conclusions of the past.}, } @article {pmid18050860, year = {2007}, author = {Merler, E}, title = {[Mesothelioma incidence decreases parallel to asbestos exposure decrement or interruption: a confirmation of a dose-response relationship, with implications in public health].}, journal = {Epidemiologia e prevenzione}, volume = {31}, number = {4 Suppl 1}, pages = {46-52}, pmid = {18050860}, issn = {1120-9763}, mesh = {Asbestos/*adverse effects ; Biotransformation ; Cohort Studies ; Dose-Response Relationship, Drug ; Humans ; Incidence ; Lung Neoplasms/*epidemiology ; Mesothelioma/*epidemiology ; Mineral Fibers/*adverse effects ; Models, Theoretical ; Occupational Exposure/*statistics & numerical data ; }, abstract = {On the basis of the available evidence, several groups of experts and investigators identified a dose-response relationship between exposure to commercial types of asbestos fibres and mesothelioma risk. The first mathematical model was proposed by Peto et al. It was derived from a conceptualisation of the multistage theory of cancer and provides an interpretation of the risk for the occurrence of mesothelioma in cohorts of exposed workers. In the study described in this paper, the author reviewed the data suggesting a decrease in mesotheliomas rate follosing reduction or interruption of exposure. Descriptive analyses and the few available long-term cohort studies indicate a decrease in risk. This is supported also by the fact that even the most biopersistent asbestos fibres are eliminated from the lungs. Indeed, a slow but effective reduction of risk has been demonstrated in the cohort of Wittenoom workers in Australia, previously exposed to crocidolite.}, } @article {pmid18050859, year = {2007}, author = {Mollo, F and Tomatis, L}, title = {[Asbestos fibers and mesothelioma pathogenesis].}, journal = {Epidemiologia e prevenzione}, volume = {31}, number = {4 Suppl 1}, pages = {43-45}, pmid = {18050859}, issn = {1120-9763}, mesh = {Asbestos/*adverse effects ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Mineral Fibers/*adverse effects ; }, } @article {pmid18050858, year = {2007}, author = {Mocciola, M}, title = {[Criminal responsibility in non pre-meditated personal injury caused by inhalation of asbestos].}, journal = {Epidemiologia e prevenzione}, volume = {31}, number = {4 Suppl 1}, pages = {38-40}, pmid = {18050858}, issn = {1120-9763}, mesh = {Asbestos/*adverse effects ; Criminal Law ; Humans ; Italy ; *Liability, Legal ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; }, } @article {pmid18050856, year = {2007}, author = {Bottazzi, M}, title = {[The work of the social security and welfare branch of the Trade Union supporting workers suffering from mesothelioma and asbestos related diseases].}, journal = {Epidemiologia e prevenzione}, volume = {31}, number = {4 Suppl 1}, pages = {31-34}, pmid = {18050856}, issn = {1120-9763}, mesh = {*Asbestosis/epidemiology/etiology ; Humans ; Italy ; Labor Unions ; *Mesothelioma/epidemiology/etiology ; *Occupational Diseases/epidemiology/etiology ; *Social Security ; *Social Welfare ; *Workers' Compensation ; }, } @article {pmid18050855, year = {2007}, author = {Mensi, C and Macchione, M and Termine, L and Canti, Z and Rivolta, G and Riboldi, L and Chiappino, G}, title = {[Asbestos exposure in the non-asbestos textile industry: the experience of the Lombardy Mesothelioma Registry].}, journal = {Epidemiologia e prevenzione}, volume = {31}, number = {4 Suppl 1}, pages = {27-30}, pmid = {18050855}, issn = {1120-9763}, mesh = {Aged ; Asbestos/adverse effects/*analysis ; Female ; Humans ; Italy ; Male ; Mesothelioma/*epidemiology/etiology ; Occupational Exposure/adverse effects/*statistics & numerical data ; *Registries ; *Textile Industry ; }, abstract = {The Lombardy Mesothelioma Registry, activated in 2000, receives more than 300 cases per year of suspected malignant mesothelioma; the standardized (age and gender) incidence rate of pleural mesothelioma is 2.4/100,000 inhabitants (CI 95% 2.0-2.7). The finding of an increasing number of cases among workers of the non-asbestos-textile industry, classified as "unknown exposure to asbestos", upheld the suspect of presence of asbestos in this compartment. Specific information about a possible asbestos exposure were collected by technicians, maintenance personnel and other experts; industrial machinery utilized in the past was thoroughly examined; direct inspections were carried out in several workplaces that had not yet undergone significant changes with respect to the past. A large amount of asbestos had been regularly used on the ceilings and also to the walls of factories in order to avoid both condensation of steam and reflection of noise. In addition, asbestos had also been widely used to insulate water and steam pipes. The braking systems of most of machines also had asbestos gaskets, and on several looms some brakes operated continuously. The population in study was composed of 119 subjects, 27 males and 92 females, median age of 72 years. Asbestos exposure was ascribed to work in 106 cases (89%). The system devised by the Lombardy Registry had brought to light an occupational hazard in a professional area previously never believed as a source of asbestos exposure. In consideration of the described experience, both environmental and clinical, it seems reasonable to consider the non-asbestos-textile as a new department at risk for asbestos exposure.}, } @article {pmid18050854, year = {2007}, author = {Marinaccio, A and Binazzi, A and Cauzillo, G and Chellini, E and De Zotti, R and Gennaro, V and Menegozzo, M and Mensi, C and Merler, E and Mirabelli, D and Musti, M and Pannelli, F and Romanelli, A and Scarselli, A and Tosi, S and Tumino, R and Nesti, M and , }, title = {[Epidemiological surveillance of malignant mesothelioma cases in Italy: incidence and asbestos exposure figures by the Italian mesothelioma registry (ReNaM)].}, journal = {Epidemiologia e prevenzione}, volume = {31}, number = {4 Suppl 1}, pages = {23-26}, pmid = {18050854}, issn = {1120-9763}, mesh = {Aged ; Asbestos/*adverse effects ; Female ; Humans ; Incidence ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology/*etiology ; Middle Aged ; Occupational Diseases/*epidemiology/*etiology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*epidemiology/*etiology ; Population Surveillance ; Registries ; }, abstract = {The Study describes the epidemiological surveillance of mesothelioma cases carried out by the Italian mesothelioma register (ReNaM). A Regional Operating Centre (COR) is present in nearly all Italian regions (17 out of 20) and it collects malignant mesothelioma cases and investigate the modalities of asbestos exposure by using a structured questionnaire. The register produces malignant mesothelioma incidence measures and analyses of the modalities of the asbestos exposure. The standardized incidence rate of malignant mesothelioma in 2001 was 2.98 (in 100,000 inhabitants) among men and 0.98 among women; a professional (certain, probable, possible) exposure has been detected in 67.4% of defined cases. In addition to the conventional sectors (shipbuilding, railways repair and demolition, asbestos-cement production), also textile, building, transport, chemical and glass industries, petroleum and sugar refineries, electricity production and distribution plants are getting involved. Despite the absence of some regions completing the national coverage and the non homogeneity in collecting and coding data, the epidemiological surveillance of malignant mesothelioma carried out by ReNaM is an important tool for the scientific knowledge and the prevention of asbestos-related diseases.}, } @article {pmid18050853, year = {2007}, author = {Barbieri, PG and Somigliana, A and Caironi, M and Migliori, M}, title = {[The epidemiologic surveillance of malignant mesothelioma in the Lower Iseo Lake area].}, journal = {Epidemiologia e prevenzione}, volume = {31}, number = {4 Suppl 1}, pages = {16-22}, pmid = {18050853}, issn = {1120-9763}, mesh = {Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Female ; Humans ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology/*etiology ; Middle Aged ; Occupational Diseases/*epidemiology/*etiology ; Pleural Neoplasms/*epidemiology/*etiology ; Population Surveillance ; }, abstract = {Starting from an hospital observation of the mesotheliomas cluster in women living in a lakeside area (Iseo lake, Northern Italy), an epidemiological surveillance of this tumour was performed by the local occupational health service. This cluster wasn't notified, in spite of the relevant number of factories producing asbestos textile materials in this area. From 1977 to august 2006, 45 cases of mesothelioma were detected among the workers of 3 textile industries located in 3 little villages: 14 cases occurred working crocidolite and chrysotile rope and gasket; 20 cases in a textile factory producing cotton garments, that was adjacent to and polluted by the farmer and were asbestos insulation and blankets used for fireproofing are present; 11 cases occurred among women working in silk factories. The mesothelioma cases occurred in the same period in this area, which constituted the recruitment area of the people working in the 3 textile plants (11 villages, about 43,000 inhabitants), are 55.93% of which had been occupationally exposed to asbestos. Out of the dockyard and the asbestos-cement industries, this frequency of occupational exposed workers is the highest never observed in Italy. The majority of the cases (66%) occurred among women working in the textile factories. In a women, producing asbestos textile materials and suffered form peritoneal mesothelioma and pleural plaques, the analysis (by SEM) of asbestos fibre lung burden show 286 million fibres x gr. of dry tissue. Between the 42 mesothelioma cases occurring in the population of the 3 villages where the textile plants was located, we observed only one case with possible environmental exposure to asbestos: a gardener of the village where the manufacturing asbestos ropes and gasket plant is present. In the silk factories, asbestos exposure was probable because of the presence of asbestos insulated pipes. The female pleural mesothelioma standard incidence observed in this area (6.8 x 100,000, 1977-2005) is the highest never estimate in Italy. The epidemiological surveillance of the mesothelioma appear essential to identify cases unreported and allow the collection of information useful to understand clearly the asbestos exposure effects on health's workers and to estimate the tumour incidence in the population.}, } @article {pmid18050852, year = {2007}, author = {Caironi, M and Polini, S and Storto, T and Bertoli, M}, title = {[The productive district of textile asbestos in the Lower Iseo Lake area].}, journal = {Epidemiologia e prevenzione}, volume = {31}, number = {4 Suppl 1}, pages = {10-15}, pmid = {18050852}, issn = {1120-9763}, mesh = {Asbestos/*adverse effects ; Humans ; Italy ; Occupational Exposure/*adverse effects ; *Textile Industry ; }, abstract = {In the Bergamo area of Basso Sebino (lower Lake Iseo), for decades there has been a large concentration of small firms (mostly family-run), specialised in the production of rubber gaskets. Within this production field, some companies used to manufacture textile asbestos exclusively or as part of their business. The asbestos goods were therefore marketed as they were or subsequently cut and transformed into gaskets. Among the 5 companies involved, "Manifattura Colombo & C" was the first one that started this production in the district, and the one that engaged the greatest number of employees (considering both the Sarnico and Predore factories). In the Predore factory, operating from the fifties to 1979, the asbestos thread production was carried out exclusively and to the complete technological cycle (i.e. from crashing the raw asbestos that was brought in from Balangero). The whole process was performed in an extremely dusty environment (according to the witness of former workers), expecially during the first production steps. In the Sarnico factory which operated from 1920 to 1993, they produced textile asbestos items (laces, ropes, etc.), as well as rubber and metal gaskets. The latter were coupled with asbestos by means of metal-plastics co-moulding operations, in order to obtain gaskets highly resistant to exhaust vapours, gases, oils, solvents and so on. The environmental data available (referred to the 1980-1992 period), supply evidence of severe exposure in the first years of activity, whilst a sharp reduction in the asbestos-fiber concentration rate was achieved along the years, thanks mainly to the completion and improvement of exhaust systems installed on winding and braiding machines. Finally we shortly describe the work of the four other factories and in more detail that of the "Manifattura Sebina srl" is mentioned herein because, although this is a "typical" textile mill and exclusively manufacturing cotton products, a considerable number of cases of mesothelioma has been detected among its workforce. This has been attributed to the presence of asbestos insulated piping, to maintenance and replacement interventions on looms brake pads, and above all to the nearly 50 asbestos blankets that were employed in the weekly fire-fighting exercises, and usually leaned against the walls of departments, with no protection whatsoever.}, } @article {pmid18045848, year = {2008}, author = {Musk, AW and de Klerk, NH and Reid, A and Ambrosini, GL and Fritschi, L and Olsen, NJ and Merler, E and Hobbs, MS and Berry, G}, title = {Mortality of former crocidolite (blue asbestos) miners and millers at Wittenoom.}, journal = {Occupational and environmental medicine}, volume = {65}, number = {8}, pages = {541-543}, doi = {10.1136/oem.2007.034280}, pmid = {18045848}, issn = {1470-7926}, mesh = {Aged ; Asbestos, Crocidolite/*toxicity ; Asbestosis/mortality ; Cause of Death ; Follow-Up Studies ; Humans ; Italy/ethnology ; Lung Neoplasms/mortality ; Male ; Mesothelioma/*mortality ; *Mining ; Occupational Exposure/*adverse effects ; Peritoneal Neoplasms/*mortality ; Pleural Neoplasms/mortality ; Respiratory Tract Diseases/*mortality ; Western Australia/epidemiology ; }, abstract = {BACKGROUND: Blue asbestos was mined and milled at Wittenoom in Western Australia between 1943 and 1966.

METHODS: Nearly 7000 male workers who worked at the Wittenoom mine and mill have been followed up using death and cancer registries throughout Australia and Italy to the end of 2000. Person-years at risk were derived using two censoring dates in order to produce minimum and maximum estimates of asbestos effect. Standardised mortality ratios (SMRs) compare the mortality of the former Wittenoom workers with the Western Australian male population.

RESULTS: There have been 190 cases of pleural and 32 cases of peritoneal mesothelioma in this cohort of former workers at Wittenoom. Mortality from lung cancer (SMR = 1.52), pneumoconiosis (SMR = 15.5), respiratory diseases (SMR = 1.58), tuberculosis (SMR = 3.06), digestive diseases (SMR = 1.47), alcoholism (SMR = 2.24) and symptoms, signs and ill defined conditions (SMR = 2.00) were greater in this cohort compared to the Western Australian male population.

CONCLUSION: Asbestos related diseases, particularly malignant mesothelioma, lung cancer and pneumoconiosis, continue to be the main causes of excess mortality in the former blue asbestos miners and millers of Wittenoom.}, } @article {pmid18042928, year = {2007}, author = {}, title = {StatBite: Mesothelioma incidence among U.S. men.}, journal = {Journal of the National Cancer Institute}, volume = {99}, number = {23}, pages = {1751}, doi = {10.1093/jnci/djm253}, pmid = {18042928}, issn = {1460-2105}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asbestos/toxicity ; Carcinogens ; Child ; Child, Preschool ; Humans ; Incidence ; Infant ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; SEER Program ; United States/epidemiology ; }, } @article {pmid18042927, year = {2007}, author = {Burkitt, V}, title = {In Australia, patients and government at odds over mesothelioma treatment costs.}, journal = {Journal of the National Cancer Institute}, volume = {99}, number = {23}, pages = {1750-1752}, doi = {10.1093/jnci/djm257}, pmid = {18042927}, issn = {1460-2105}, mesh = {Abdominal Neoplasms/economics/therapy ; Antimetabolites, Antineoplastic/administration & dosage/economics ; Antineoplastic Combined Chemotherapy Protocols/*economics/therapeutic use ; Asbestos/toxicity ; Australia/epidemiology ; Canada ; Carcinogens ; Cisplatin/administration & dosage/economics ; Cost-Benefit Analysis ; Environmental Exposure/adverse effects ; Glutamates/administration & dosage/economics ; *Government ; Guanine/administration & dosage/analogs & derivatives/economics ; *Health Care Costs ; Humans ; Incidence ; Lobbying ; Lung Neoplasms/economics/therapy ; Mesothelioma/*economics/epidemiology/etiology/*therapy ; *Patient Advocacy ; Pemetrexed ; Quinazolines/administration & dosage/economics ; Thiophenes/administration & dosage/economics ; Thoracic Neoplasms/economics/therapy ; United Kingdom ; }, } @article {pmid18039530, year = {2007}, author = {Motadi, LR and Misso, NL and Dlamini, Z and Bhoola, KD}, title = {Molecular genetics and mechanisms of apoptosis in carcinomas of the lung and pleura: therapeutic targets.}, journal = {International immunopharmacology}, volume = {7}, number = {14}, pages = {1934-1947}, doi = {10.1016/j.intimp.2007.07.013}, pmid = {18039530}, issn = {1567-5769}, mesh = {Angiogenesis Inhibitors/pharmacology ; Antineoplastic Agents/therapeutic use ; Apoptosis/*drug effects/genetics ; Carcinoma/drug therapy/genetics ; Caspases/drug effects ; Genes, Tumor Suppressor/drug effects ; *Genetic Therapy ; Humans ; Lung Neoplasms/*drug therapy/*genetics ; Male ; Mesothelioma/drug therapy/genetics ; Neovascularization, Pathologic/drug therapy ; Pleural Neoplasms/*drug therapy/*genetics ; }, abstract = {Cancers of the lung and pleura remain a major cause of cancer deaths, both in men and women, with strong causal relationships between cigarette smoking and asbestos fibres, and deaths from lung cancer and mesothelioma, respectively. The poor survival rates for small cell lung cancer and mesotheliomas argue powerfully for greater understanding of mechanisms of carcinogenesis, genetic abnormalities and the role of tumour suppressor genes and proteins in carcinomas of the lung and pleura. Despite progress in the development of newer cytotoxic drugs, lung cancer remains a lethal disease. Chemotherapy and radiotherapy produce only a modest improvement in survival of patients with advanced disease. Increased knowledge of molecular mechanisms of lung cancer and apoptosis are providing opportunities for treating lung cancer with new classes of molecularly targeted drugs. These novel therapies should target the abnormalities in lung cancer by maximizing the effects of anti-tumour molecules, with minimal side effects on normal tissues. Of the several molecular targets, those receiving attention are p53 gene replacement, Bcl-2 downregulation, apoptosis by induced by TNF, the FAS/CD95 receptor system and TRAIL, and inhibition of NF-kappaB. Although several studies have shown benefits, there is a need for well planned clinical trials of drugs that target the apoptotic cascade. Stem cell therapy and gene replacement offer the prospect of novel approaches that are likely in the near future to play a definitive role in the treatment of advanced lung cancer. Furthermore, with their apparent minimal toxicity to normal tissues, the newer molecular targets represent attractive investigational directions for innovative cancer therapies.}, } @article {pmid17965072, year = {2007}, author = {, }, title = {BTS statement on malignant mesothelioma in the UK, 2007.}, journal = {Thorax}, volume = {62 Suppl 2}, number = {Suppl 2}, pages = {ii1-ii19}, pmid = {17965072}, issn = {0040-6376}, mesh = {Antineoplastic Agents/therapeutic use ; Asbestos/toxicity ; Biomarkers/blood ; Clinical Trials, Phase II as Topic ; Communication ; Diagnosis, Differential ; Diagnostic Imaging/methods ; Disability Evaluation ; Dyspnea/prevention & control ; Health Services Accessibility/organization & administration ; Humans ; *Mesothelioma/diagnosis/mortality/therapy ; Nurse Clinicians/statistics & numerical data ; Nurse's Role ; *Occupational Diseases/diagnosis/mortality/therapy ; Pain/prevention & control ; Palliative Care/methods ; Patient Education as Topic ; Patient-Centered Care ; Pensions ; *Peritoneal Neoplasms/diagnosis/mortality/therapy ; Physical Examination ; Pleural Effusion/therapy ; *Pleural Neoplasms/diagnosis/mortality/therapy ; Prognosis ; Social Support ; Survival Analysis ; Workers' Compensation/economics/legislation & jurisprudence ; }, } @article {pmid18038314, year = {2008}, author = {Tutar, E and Kiyici, H}, title = {Role of fragile histidine triad protein expression in pathogenesis of malignant pleural mesothelioma.}, journal = {Pathology}, volume = {40}, number = {1}, pages = {42-45}, doi = {10.1080/00313020701716383}, pmid = {18038314}, issn = {0031-3025}, mesh = {Acid Anhydride Hydrolases/*metabolism ; Adult ; Aged ; Aged, 80 and over ; Asbestos ; Carcinogens ; Cell Proliferation ; Female ; Humans ; Ki-67 Antigen/metabolism ; Male ; Mesothelioma/chemically induced/*metabolism/pathology ; Middle Aged ; Neoplasm Proteins/*metabolism ; Pleural Neoplasms/chemically induced/*metabolism/pathology ; }, abstract = {AIM: To investigate the relationship of fragile histidine triad (FHIT) and Ki-67 expression with clinicopathological variables of patients with malignant pleural mesothelioma (MPM).

METHODS: Formalin-fixed, paraffin-embedded tissue sections of 30 asbestos induced MPM (epithelial and biphasic) patients were examined for FHIT and Ki-67 expression using immunohistochemical techniques and results were compared with clinicopathological variables.

RESULTS: Immunohistochemical study results were as follows: 12 (40%) cases showed low FHIT expression and 18 (60%) showed high expression. There was no significant relationship between FHIT and age, gender or histological subtypes (p > 0.05). Ki-67 expression was 'low' in 13 (43.3%) cases and 'high' in 17 (56.7%) cases. No correlation could be demonstrated between Ki-67 expression and age, gender or histological subtypes (p > 0.05). No significant association was observed between FHIT and Ki-67 expression in MPM.

CONCLUSION: The results support the role of FHIT as a tumour suppressor gene in asbestos induced MPM. There is no significant correlation between FHIT and cell proliferation marker expressions in malignant pleural mesothelioma. Therefore, it can be concluded that loss of FHIT does not interfere with tumour proliferation. This can be accepted as evidence for an early role of FHIT loss in carcinogenesis; however, it needs to be strengthened by further studies.}, } @article {pmid18035012, year = {2007}, author = {Tenaglia, L and Proietti, L and Calì, S and Trovato, S and Accurso, N and Di Stefano, C and Catania, G}, title = {Peritoneal malignant mesothelioma: case report.}, journal = {Il Giornale di chirurgia}, volume = {28}, number = {11-12}, pages = {435-438}, pmid = {18035012}, issn = {0391-9005}, mesh = {Adenocarcinoma/etiology/surgery ; Adult ; Asbestos/adverse effects ; Environmental Exposure/adverse effects ; Frozen Sections ; Genetic Predisposition to Disease ; Humans ; Male ; Mesothelioma/*etiology/*surgery ; Peritoneal Neoplasms/*etiology/*surgery ; Polyomavirus Infections/complications ; Simian virus 40 ; Tumor Virus Infections/complications ; }, abstract = {Our study reports peritoneal diffuse malignant mesothelioma (DMM) in a 43 years old male patient, with no exposure to asbestos in his medical history; the partner of the patient was also not exposed to asbestos. The exposure to X-rays was also excluded. Different pathogenic mechanisms for the pathogenesis of a peritoneal diffuse malignant mesothelioma in this patient can be hypothesized, for example, SV40 infection and genetic susceptibility; a minimal domestic exposure to asbestos can be not excluded. Therefore, further studies in a larger number of subjects are necessary to determine whether one or all of these hypothetic pathogenic mechanisms are more significant for the development of malignant mesothelioma.}, } @article {pmid18023951, year = {2008}, author = {White, N and Nelson, G and Murray, J}, title = {South African experience with asbestos related environmental mesothelioma: is asbestos fiber type important?.}, journal = {Regulatory toxicology and pharmacology : RTP}, volume = {52}, number = {1 Suppl}, pages = {S92-6}, doi = {10.1016/j.yrtph.2007.09.013}, pmid = {18023951}, issn = {1096-0295}, mesh = {Asbestos/*adverse effects/classification ; Asbestos, Amosite/adverse effects/classification ; Asbestos, Crocidolite/adverse effects/classification ; Asbestosis/epidemiology/*etiology ; Carcinogens/classification/*toxicity ; Environmental Exposure/*adverse effects ; Female ; Humans ; Male ; Mesothelioma/epidemiology/*etiology ; Mineral Fibers/adverse effects/classification ; Mining ; Occupations ; South Africa/epidemiology ; }, abstract = {South Africa (SA), a country in which all three commercially important asbestos minerals have been mined and milled, has retained proven cases of mesothelioma linked with environmental exposure to asbestos. This study illustrates the importance of fiber type in the occurrence of environmental mesothelioma. Four studies have reviewed the source of occupational or environmental asbestos exposure in 504 histologically proven cases of mesothelioma in South Africa. One hundred and eighteen cases (23%) were thought to be related to environmental exposure to asbestos. In the vast majority of these cases, exposure was linked to crocidolite mining activities in the Northern Cape Province. Two cases were thought to have occurred in relation to amosite and Transvaal crocidolite exposure in the Limpopo Province. In the balance of cases there was some uncertainty. No cases were reported with exposure to South African chrysotile. Consequently, in the vast majority of cases of mesothelioma, environmental exposure to asbestos occurred in the Northern Cape Province, in proximity to mines, mills and dumps where crocidolite was processed. Crocidolite appears to be far more mesotheliomagenic than amosite, and chrysotile has not been implicated in the disease. This is true for both occupationally and environmentally exposed individuals.}, } @article {pmid18023950, year = {2008}, author = {Murray, J and Nelson, G}, title = {Health effects of amosite mining and milling in South Africa.}, journal = {Regulatory toxicology and pharmacology : RTP}, volume = {52}, number = {1 Suppl}, pages = {S75-81}, doi = {10.1016/j.yrtph.2007.09.011}, pmid = {18023950}, issn = {1096-0295}, mesh = {Asbestos, Amosite/*adverse effects ; Asbestosis/epidemiology/*etiology/history ; Environmental Exposure/*adverse effects/history ; Female ; History, 20th Century ; Humans ; Male ; Mesothelioma/*chemically induced/epidemiology ; Mineral Fibers/adverse effects ; *Mining ; South Africa/epidemiology ; Space-Time Clustering ; }, abstract = {This study focuses on the amosite mining region in South Africa and associated health effects, compared to other mined asbestos fiber types. Historically, dust and fiber levels were high in the amosite mills and mines, and many miners and members of the surrounding communities were exposed to the fibers. Research has shown that amosite produces both benign and malignant disease. Nevertheless, the mesotheliomagenic potential of amosite is several fold lower than crocidolite. The risk of disease associated with amosite exposure is difficult to quantify. Reasons for this include the scarcity of available information, including fiber measurements, and case ascertainment, as well as the juxtaposition of the amosite and crocidolite asbestos seams in South Africa.}, } @article {pmid18022741, year = {2008}, author = {Ribak, J and Ribak, G}, title = {Human health effects associated with the commercial use of grunerite asbestos (amosite): Paterson, NJ; Tyler, TX; Uxbridge, UK.}, journal = {Regulatory toxicology and pharmacology : RTP}, volume = {52}, number = {1 Suppl}, pages = {S82-90}, doi = {10.1016/j.yrtph.2007.10.002}, pmid = {18022741}, issn = {1096-0295}, mesh = {Air Pollutants, Occupational/*adverse effects/analysis/pharmacokinetics ; Animals ; Asbestos, Amosite/*adverse effects/analysis/pharmacokinetics ; Asbestosis/*etiology ; Cohort Studies ; Disease Models, Animal ; Humans ; Lung/chemistry/drug effects/metabolism ; Lung Neoplasms/etiology/metabolism/mortality ; Mesothelioma/etiology/metabolism/mortality ; New Jersey/epidemiology ; Texas/epidemiology ; United Kingdom/epidemiology ; }, abstract = {Grunerite asbestos (amosite) has been shown in epidemiological and experimental animal studies to cause lung cancer, mesothelioma and pulmonary fibrosis commonly referred to as asbestosis. An overview of the human and experimental animal studies describing the health hazards of grunerite asbestos (amosite) is presented. Of the many human studies describing the health hazards of asbestos, only three factories using mainly, if not exclusively, grunerite asbestos (amosite) have been studied. The first is a series of reports on a cohort of 820 workers from a plant located in Paterson, NJ. Among this cohort, 18.7% died of lung cancer and 17 mesotheliomas occurred. The Paterson factory closed in 1954 and moved to Tyler, Texas where it operated until 1972. Among the 1130 former workers in the Tyler plant 6 mesotheliomas were reported with 15.8% lung cancer mortality. The third grunerite asbestos (amosite) exposed cohort was an insulation board manufacturing facility in Uxbridge, United Kingdom. Here 17.1% of the workers died of lung cancer and 5 mesotheliomas occurred. The lung content from 48 Uxbridge workers was analyzed by analytical transmission electron microscopy for mineral fibers. The relationship between grunerite asbestos (amosite) concentrations in the lung correlated with grades of fibrosis and asbestos bodies and was lower than the concentration found in the cases with malignant tumors. The lung cancer cases contained more grunerite asbestos (amosite) than mesothelioma cases, and in the cases of non-malignant disease the concentrations were still lower. In both types of malignancies the concentration of grunerite asbestos (amosite) was very high-over a billion fibers per gram of dried lung tissue. Occupational exposure to airborne concentrations of between 14 and 100 fibers of grunerite asbestos (amosite) per milliliter after 20 year latency causes marked increases in lung cancer, mesothelioma and pulmonary fibrosis (asbestosis).}, } @article {pmid18022298, year = {2008}, author = {Gibbs, GW and Berry, G}, title = {Mesothelioma and asbestos.}, journal = {Regulatory toxicology and pharmacology : RTP}, volume = {52}, number = {1 Suppl}, pages = {S223-31}, doi = {10.1016/j.yrtph.2007.10.003}, pmid = {18022298}, issn = {1096-0295}, mesh = {Air Pollutants, Occupational/*adverse effects ; Asbestos/*adverse effects/classification ; Asbestos, Amphibole/adverse effects ; Asbestosis/epidemiology/*etiology ; Carcinogens, Environmental/*adverse effects ; Dose-Response Relationship, Drug ; Humans ; Iron/adverse effects ; Mesothelioma/epidemiology/*etiology ; Mineral Fibers/adverse effects/classification ; Particle Size ; Risk Assessment ; Silicates/adverse effects ; }, abstract = {The current state of knowledge concerning mesothelioma risk estimates is reviewed. Estimates of the risk of mesothelioma exist for the commercial asbestos fiber types chrysotile, amosite and crocidolite. Data also exist on which to assess risks for winchite (sodic tremolite) and anthophyllite asbestos. Uncertainty in estimates is primarily related to limitations in measurements of exposure. Differences in the dimensions of the various fiber types and of the same fiber types at different stages of processing add a further complication. Never-the-less, in practical terms, crocidolite presents the highest asbestos related mesothelioma risk. The risk associated with sodic tremolite (winchite) appears to be similar. In chrysotile miners and millers, the mesothelioma risk has been linked with exposure to asbestiform tremolite. Exposure to chrysotile in a pure form seems likely to present a very low if any risk of mesothelioma. While the majority of mesothelial tumors result from exposure to the asbestos minerals, there are other well established and suspected etiological agents. While a practical threshold seems to exist for exposure to chrysotile, it is unlikely to exist for the amphibole asbestos minerals, especially for crocidolite. To date there is no indication of an increased risk of mesothelioma resulting from non-commercial fiber exposure in the taconite industry.}, } @article {pmid18008340, year = {2007}, author = {Ampleford, EJ and Ohar, J}, title = {Mesothelioma: you do not have to work for it.}, journal = {Diagnostic cytopathology}, volume = {35}, number = {12}, pages = {774-777}, doi = {10.1002/dc.20766}, pmid = {18008340}, issn = {8755-1039}, mesh = {Adolescent ; Adult ; Air Pollution, Indoor/adverse effects ; Asbestos/*adverse effects ; Child ; Clothing ; Environmental Exposure/*adverse effects ; Female ; Humans ; Laundering ; Mesothelioma/*etiology/pathology/physiopathology ; Middle Aged ; Nuclear Family ; Peritoneal Neoplasms/*etiology/pathology/physiopathology ; Pleural Neoplasms/*etiology/pathology/physiopathology ; }, abstract = {Asbestos pollution is a global problem. Asbestos exposure induced mesothelioma does not require an 'occupational' type of exposure. Bystander exposures may result in earlier age of disease onset and more aggressive disease progression as described in the following 3 case reports.}, } @article {pmid18000381, year = {2007}, author = {Vauhkonen, H and Heino, S and Myllykangas, S and Lindholm, PM and Savola, S and Knuutila, S}, title = {Etiology of specific molecular alterations in human malignancies.}, journal = {Cytogenetic and genome research}, volume = {118}, number = {2-4}, pages = {277-283}, doi = {10.1159/000108311}, pmid = {18000381}, issn = {1424-859X}, mesh = {Asbestos/*toxicity ; Carcinogens/*toxicity ; Chromatin/genetics ; DNA/genetics ; Helicobacter pylori/*pathogenicity ; Humans ; Neoplasms/diagnosis/*genetics/microbiology ; }, abstract = {Cancer results from multiple genomic changes that affect DNA and its gene expression. The DNA sequences may be gained, lost or amplified, or translocated into different parts of the genome to form a fusion gene with oncogenic properties. The occurrence of specific chromosomal aberrations may be restricted to only one cancer type and it may be considered a primary carcinogenic event. Furthermore, the aberration profiles may be used to cluster tumors with similar origins. A variety of techniques exist for the detection of specific chromosomal and gene expression changes. However, the etiology of these molecular alterations remains unclear. Here we discuss the roles of Helicobacter pylori and asbestos burden as carcinogens that cause gastric cancer, mesothelioma and lung cancer.}, } @article {pmid17998152, year = {2008}, author = {Berry, G and Gibbs, GW}, title = {An overview of the risk of lung cancer in relation to exposure to asbestos and of taconite miners.}, journal = {Regulatory toxicology and pharmacology : RTP}, volume = {52}, number = {1 Suppl}, pages = {S218-22}, doi = {10.1016/j.yrtph.2007.09.012}, pmid = {17998152}, issn = {1096-0295}, mesh = {Air Pollutants, Occupational/*adverse effects ; Asbestos/*adverse effects/classification ; Carcinogens, Environmental/*adverse effects ; Dose-Response Relationship, Drug ; Humans ; Iron/*adverse effects ; Lung Neoplasms/epidemiology/*etiology ; Mesothelioma/epidemiology/*etiology ; Meta-Analysis as Topic ; Mineral Fibers/adverse effects/classification ; *Mining ; Occupational Exposure/adverse effects/analysis ; Particle Size ; Risk ; Risk Assessment ; Silicates/*adverse effects ; }, abstract = {Exposure-response relationships between the relative risk of lung cancer and quantitative measures of exposure to asbestos are available from a number of epidemiological studies. Meta-analyses of these relationships have been published by Lash et al. (1997) [Lash, T.L., Crouch, E.A.C., Green, L.C., 1997. A meta-analysis of the relation between cumulative exposure to asbestos and relative risk of lung cancer. Occup. Environ. Med. 54, 254-263] and Hodgson and Darnton (2000) [Hodgson, J.T., Darnton, A., 2000. The quantitative risks of mesothelioma and lung cancer in relation to asbestos exposure. Ann. Occup. Hyg. 44, 565-601]. In this paper, the risks derived in these meta-analyses have been compared. Lash et al., concentrated on process and found that the risk of lung cancer increased as the asbestos is refined by processing. Hodgson and Darnton concentrated on fibre type and found that the risk was highest for exposure to amphibole asbestos (crocidolite and amosite), lowest for chrysotile and intermediate for mixed exposure. Some of the differences between the conclusions from the two meta-analyses are a consequence of the choice of studies included. The range of asbestos types included in the studies in the analysis of Hodgson and Darnton was wider than that in Lash et al., enabling differences between fibre types to be analyzed more readily. There are situations where occupational exposure to chrysotile asbestos has shown no detectable increase in risk of lung cancer. Taconite miners have shown no increased risk of mortality due to lung cancer.}, } @article {pmid17988773, year = {2008}, author = {Brunner, WM and Williams, AN and Bender, AP}, title = {Investigation of exposures to commercial asbestos in northeastern Minnesota iron miners who developed mesothelioma.}, journal = {Regulatory toxicology and pharmacology : RTP}, volume = {52}, number = {1 Suppl}, pages = {S116-20}, doi = {10.1016/j.yrtph.2007.09.014}, pmid = {17988773}, issn = {1096-0295}, mesh = {Aged ; Aged, 80 and over ; Air Pollutants, Occupational/*adverse effects ; Asbestos/*adverse effects ; Asbestosis/epidemiology/*etiology/pathology ; Databases, Factual ; Female ; Humans ; Male ; Mesothelioma/epidemiology/*etiology/pathology ; Middle Aged ; *Mining ; Minnesota/epidemiology ; Peritoneal Neoplasms/epidemiology/*etiology/pathology ; Pleural Neoplasms/epidemiology/*etiology/pathology ; }, abstract = {A 70% excess of mesothelioma, an asbestos-related cancer, has been reported among men in northeastern Minnesota, where iron mining has been the major industry. The Minnesota Department of Health has studied iron miners who developed mesothelioma to identify possible sources of asbestos exposure. A database of all Minnesota residents diagnosed with mesothelioma between 1988 and 1996 was linked to a database of approximately 72,000 current and former Minnesota iron-mining employees to identify cases who had ever worked in the mining industry. The job histories of the cases were examined to determine if any of their jobs could have involved exposure to commercial asbestos. Seventeen individuals diagnosed with mesothelioma in Minnesota between 1988 and 1996 were found to have worked in the iron mining industry. Of the 15 for whom adequate work histories were available, 14 had identifiable sources of exposure to commercial asbestos in jobs held both inside and outside of the mining industry. The time between employment in these asbestos-exposed occupations and the diagnosis of mesothelioma is consistent with the 20 or more year latency period that has been observed in other studies of this cancer.}, } @article {pmid17980576, year = {2007}, author = {Marinaccio, A and Binazzi, A and Cauzillo, G and Cavone, D and Zotti, RD and Ferrante, P and Gennaro, V and Gorini, G and Menegozzo, M and Mensi, C and Merler, E and Mirabelli, D and Montanaro, F and Musti, M and Pannelli, F and Romanelli, A and Scarselli, A and Tumino, R and , }, title = {Analysis of latency time and its determinants in asbestos related malignant mesothelioma cases of the Italian register.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {43}, number = {18}, pages = {2722-2728}, doi = {10.1016/j.ejca.2007.09.018}, pmid = {17980576}, issn = {0959-8049}, mesh = {Adult ; Aged ; Asbestos/*toxicity ; Environmental Exposure/*adverse effects ; Epidemiologic Methods ; Female ; Heart Neoplasms/*epidemiology ; Humans ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Pericardium ; Peritoneal Neoplasms/*epidemiology ; Pleural Neoplasms/*epidemiology ; Testicular Neoplasms/*epidemiology ; Time Factors ; }, abstract = {Italy was an important producer of raw asbestos until 1992 (when it was banned) and it is now experiencing severe public health consequences due to large-scale industrial use of asbestos in shipbuilding and repair, asbestos-cement production, railways, buildings, chemicals and many other industrial sectors. Latency of malignant mesothelioma generally shows a large variability and the relationship with the modality of asbestos exposure is still not fully clarified. We present an analysis of latency period among the case list collected by the Italian mesothelioma register (ReNaM) in the period of diagnosis 1993-2001 (2544 malignant mesothelioma (MM) cases with asbestos exposure history). Exposure is assessed retrospectively by interview. Statistical univariate analyses were performed to estimate median and variability measures of latency time by anatomical site, gender and diagnosis period. The role of diagnostic confidence level, the morphology of the tumour and the modalities of asbestos exposure were verified in a regression multivariate model. We found a median latency period of 44.6 years increasing in recent years with a linear trend. Anatomical site, gender and morphology were not relevant for MM latency time whereas a shorter latency period was documented among occupationally exposed subjects (43 years) with respect to environmentally and household exposed ones (48 years).}, } @article {pmid17976017, year = {2007}, author = {Chee, J and Singh, J and Naran, A and Misso, NL and Thompson, PJ and Bhoola, KD}, title = {Novel expression of kallikreins, kallikrein-related peptidases and kinin receptors in human pleural mesothelioma.}, journal = {Biological chemistry}, volume = {388}, number = {11}, pages = {1235-1242}, doi = {10.1515/BC.2007.139}, pmid = {17976017}, issn = {1431-6730}, mesh = {Fluorescent Antibody Technique ; Humans ; Immunoenzyme Techniques ; Kallikreins/*metabolism ; Kinins/*metabolism ; Mesothelioma/enzymology/*metabolism ; Peptide Hydrolases/*metabolism ; Pleural Neoplasms/enzymology/*metabolism ; Receptors, Cell Surface/*metabolism ; }, abstract = {Malignant mesothelioma is an aggressive cancer of the pleura that is causally related to exposure to asbestos fibres. The kallikrein serine proteases [tissue (hK1) and plasma (hKB1) kallikreins, and kallikrein-related peptidases (KRP/hK2-15)] and the mitogenic kinin peptides may have a role in tumourigenesis. However, it is not known whether hK1, hKB1, KRP/hK proteins or kinin receptors are expressed in pleural mesotheliomas. The expression of hK1, hKB1, KRP/hK2, 5, 6, 7, 8 and 9, and kinin B(1) and B(2) receptors was assessed in archived selected normal tissue and mesothelioma tumour sections by immunoperoxidase and immunofluorescence labelling. hK1, hKB1 and kinin B(1) and B(2) receptors were expressed in malignant cells of the epithelioid and sarcomatoid components of biphasic mesothelioma tumour cells. The percentage of cells with cytoplasmic and nuclear labelling and the intensity of labelling were similar for hK1, hKB1 and the kinin receptors. KRP/hK2, 6, 8 and 9 were also expressed in the cytoplasm and nuclei of mesothelioma cells, whereas KRP/hK5 and hK7 showed predominantly cytoplasmic localisation. This is a first report, but further studies are required to determine whether these proteins have a functional role in the pathogenesis of mesothelioma and/or may be potential biomarkers for pleural mesothelioma.}, } @article {pmid17965448, year = {2007}, author = {Kelsh, MA and Craven, VA and Teta, MJ and Mowat, FS and Goodman, M}, title = {Mesothelioma in vehicle mechanics: is the risk different for Australians?.}, journal = {Occupational medicine (Oxford, England)}, volume = {57}, number = {8}, pages = {581-589}, doi = {10.1093/occmed/kqm114}, pmid = {17965448}, issn = {0962-7480}, mesh = {Air Pollutants, Occupational/toxicity ; Asbestos/*toxicity ; Australia/epidemiology ; *Automobiles ; Carcinogens/*toxicity ; Epidemiologic Methods ; Europe/epidemiology ; Humans ; Male ; Mesothelioma/epidemiology/*etiology ; Occupational Diseases/epidemiology/*etiology ; Occupational Exposure/*adverse effects ; United States/epidemiology ; }, abstract = {BACKGROUND: The question of whether vehicle mechanics have an increased risk of mesothelioma has important public health implications. Calculations of relative risk using case reports from the Australian Mesothelioma Registry (AMR) indicate increased risks; however, this contrasts with the results of 19 epidemiologic studies that have found no association.

AIM: To evaluate potential explanations for the discrepancy of findings from epidemiologic studies and AMR reports.

METHODS: We evaluated three hypotheses as possible explanations for the inconsistency between the AMR-based calculations and the findings from published epidemiologic studies: (i) differences in exposure characteristics of Australian vehicle mechanics versus vehicle mechanics in North America and Europe, (ii) limitations of the AMR data and (iii) errors in the risk calculations based on AMR data. We reviewed available exposure information specific to Australian vehicle mechanics and AMR data, obtained from the Australian National Occupational Health and Safety Commission, for this evaluation.

RESULTS: We did not identify differences in workplace exposures, processes or fibre type among Australian vehicle mechanics compared to vehicle mechanics in other countries. Our analysis of primary AMR data identified several errors in exposure classification and in the assumptions used to calculate relative risk.

CONCLUSIONS: Discrepancies between epidemiologic studies and AMR-based calculations cannot be explained by differences in exposure. These discrepancies are most likely attributable to inadequate occupational information and classification in the AMR from 1986 forward and to erroneous assumptions used to derive relative risk estimates for mesothelioma among Australian vehicle mechanics.}, } @article {pmid17962615, year = {2007}, author = {Fasola, G and Belvedere, O and Aita, M and Zanin, T and Follador, A and Cassetti, P and Meduri, S and De Pangher, V and Pignata, G and Rosolen, V and Barbone, F and Grossi, F}, title = {Low-dose computed tomography screening for lung cancer and pleural mesothelioma in an asbestos-exposed population: baseline results of a prospective, nonrandomized feasibility trial--an Alpe-adria Thoracic Oncology Multidisciplinary Group Study (ATOM 002).}, journal = {The oncologist}, volume = {12}, number = {10}, pages = {1215-1224}, doi = {10.1634/theoncologist.12-10-1215}, pmid = {17962615}, issn = {1083-7159}, mesh = {Adenocarcinoma/diagnostic imaging ; Adult ; Aged ; Asbestos/*adverse effects ; Carcinoma, Non-Small-Cell Lung/diagnostic imaging ; Feasibility Studies ; Female ; Humans ; Incidence ; Lung Neoplasms/*diagnostic imaging/etiology ; Male ; Mass Chest X-Ray ; Mesothelioma/*diagnostic imaging/etiology ; Middle Aged ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*diagnostic imaging/etiology ; Prognosis ; Prospective Studies ; Radiography, Thoracic ; Risk Factors ; Tomography, X-Ray Computed ; }, abstract = {OBJECTIVE: To evaluate the feasibility of using low-dose computed tomography (LDCT) for the early diagnosis of lung cancer and malignant pleural mesothelioma in an asbestos-exposed population.

METHODS: Between February 2002 and October 2003, 1,045 volunteers already enrolled in a surveillance program for asbestos-exposed workers and former workers were recruited. The main eligibility criteria were: written informed consent, definite exposure to asbestos, age 40-75, no prior cancer or severe concomitant conditions, no chest CT scan in the past 2 years. A smoking history was not required. After a structured interview, chest X-ray (CXR) and LDCT were performed. Participants with negative examinations were assigned to annual LDCT. Participants with positive findings received high-resolution CT and additional diagnostic workup as appropriate.

RESULTS: Baseline characteristics of the screened population were: median asbestos exposure time, 30 years; median age, 58; median pack-years in smokers/former smokers, 18.5. Thirty-four percent had never smoked. On LDCT, 834 noncalcified nodules were identified in 44% of participants, versus 43 nodules in 4% on CXR. Pleural abnormalities were observed in 44% and 70% of participants by CXR and LDCT, respectively. Overall, LDCT identified nine cases of non-small cell lung cancer-eight stage I, one stage IIA-and one thymic carcinoid, corresponding to 1% of the enrolled population. All cases were radically treated. None had been detected by CXR. No pleural mesothelioma was diagnosed. There were 11 false-positive results.

CONCLUSIONS: Our findings first suggest that LDCT may be at least as useful in asbestos workers as in heavy smokers for the early diagnosis of lung cancer; this benefit is evident even in a poor-risk population, with low rates of smoking prevalence and a previous history of radiological surveillance. The role of spiral tomography in screening for pleural mesothelioma remains uncertain.}, } @article {pmid17958200, year = {2007}, author = {Pelclová, D and Fenclová, Z and Urban, P}, title = {Asbestos exposure, legislation and diseases in the Czech Republic.}, journal = {Central European journal of public health}, volume = {15}, number = {3}, pages = {99-102}, doi = {10.21101/cejph.a3424}, pmid = {17958200}, issn = {1210-7778}, mesh = {Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Asbestosis/epidemiology/*etiology ; Czech Republic/epidemiology ; Female ; Humans ; Incidence ; Lung Neoplasms/*chemically induced/epidemiology ; Male ; Mesothelioma/*chemically induced/epidemiology ; Middle Aged ; Occupational Diseases/epidemiology/*etiology ; Occupational Exposure/*adverse effects ; }, abstract = {Asbestos manufacturing has been banned in the Czech Republic; however, about 280 workers in the 2nd-4th work category have been exposed during the remediation of asbestos, and the health consequences of the former use of asbestos will be apparent for many years. The incidence of mesothelioma in the Czech Republic is about 0.5/100,000 inhabitants, which places it among the lowest incidences of mesothelioma in Europe, and ranks the Czech Republic among the countries with the lowest rates in the world. The proportion of occupational mesotheliomas is only about one-tenth of these malignancies. These data show an underreporting of occupational cancers, most probably due to low awareness of the association of exposures more than 40 years ago with this disease. Physicians should focus more on the occupational history of these patients and refer them to the Departments of occupational diseases. Benefits are available for all patients with mesothelioma, in whom industrial hygienists confirm former exposure to asbestos, corresponding to the latency period.}, } @article {pmid17955087, year = {2007}, author = {Bridda, A and Padoan, I and Mencarelli, R and Frego, M}, title = {Peritoneal mesothelioma: a review.}, journal = {MedGenMed : Medscape general medicine}, volume = {9}, number = {2}, pages = {32}, pmid = {17955087}, issn = {1531-0132}, mesh = {Diagnosis, Differential ; Humans ; Mesothelioma/*diagnosis/epidemiology/*therapy ; Peritoneal Neoplasms/*diagnosis/epidemiology/*therapy ; Practice Guidelines as Topic ; Practice Patterns, Physicians' ; United States ; }, abstract = {Malignant peritoneal mesothelioma (MPM) is a rare aggressive tumor of the peritoneum, regarded as a universally fatal disease. It is poorly described and the knowledge of its natural history is very limited. Occupational and environmental asbestos exposure still remains a public health problem around the world. The incidence has increased in the past 2 decades. Only 20% to 33% of all mesotheliomas arise from the peritoneum itself; the pleura is the most common site of origin.}, } @article {pmid17954995, year = {2007}, author = {Turna, A and Pekçolaklar, A and Fener, N and Gürses, A}, title = {Localized malignant pleural mesothelioma treated by a curative intent lobectomy: a case report.}, journal = {Annals of thoracic and cardiovascular surgery : official journal of the Association of Thoracic and Cardiovascular Surgeons of Asia}, volume = {13}, number = {5}, pages = {349-351}, pmid = {17954995}, issn = {1341-1098}, mesh = {Diagnosis, Differential ; Humans ; Male ; Mesothelioma/diagnostic imaging/*surgery ; Middle Aged ; Pleural Neoplasms/diagnostic imaging/*surgery ; *Pneumonectomy ; Tomography, X-Ray Computed ; }, abstract = {Localized malignant mesothelioma is an extremely rare form of presentation of malignant mesotheliomas. The definitive therapeutic modality of the disease is yet to be identified. A 50-year-old male, a former smoker without occupational and/or environmental exposure to asbestos, presented complaining of an intractable cough. The chest radiography showed a left upper lobe mass. The computed tomography showed a 3.5 cm left apical mass. The biopsy showed epithelial malignant cells. The patient underwent a lobectomy. The evaluation of the specimen disclosed a biphasic malignant mesothelioma. His postoperative course was uneventful, and he has been doing well for almost 1 year. A resection of the tumor has shown to increase survival in previous reports, though the role of oncologically justifiable resection, such as a lobectomy, and the biological behavior of such tumors are still difficult to predict.}, } @article {pmid17953743, year = {2007}, author = {Belyanskaya, LL and Marti, TM and Hopkins-Donaldson, S and Kurtz, S and Felley-Bosco, E and Stahel, RA}, title = {Human agonistic TRAIL receptor antibodies Mapatumumab and Lexatumumab induce apoptosis in malignant mesothelioma and act synergistically with cisplatin.}, journal = {Molecular cancer}, volume = {6}, number = {}, pages = {66}, pmid = {17953743}, issn = {1476-4598}, mesh = {Antibodies, Monoclonal/*pharmacology ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents/pharmacology ; Apoptosis/*drug effects ; Cisplatin/*pharmacology ; Drug Synergism ; Flow Cytometry ; Humans ; Immunoblotting ; Jurkat Cells/drug effects/metabolism ; Mesothelioma/*drug therapy/metabolism/pathology ; Receptors, TNF-Related Apoptosis-Inducing Ligand/*immunology ; Receptors, Tumor Necrosis Factor/immunology ; }, abstract = {BACKGROUND: The incidence of malignant pleural mesothelioma (MPM) is associated with exposure to asbestos, and projections suggest that the yearly number of deaths in Western Europe due to MPM will increase until 2020. Despite progress in chemo- and in multimodality therapy, MPM remains a disease with a poor prognosis. Inducing apoptosis by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) or agonistic monoclonal antibodies which target TRAIL-receptor 1 (TRAIL-R1) or TRAIL-R2 has been thought to be a promising cancer therapy.

RESULTS: We have compared the sensitivity of 13 MPM cell lines or primary cultures to TRAIL and two fully human agonistic monoclonal antibodies directed to TRAIL-R1 (Mapatumumab) and TRAIL-R2 (Lexatumumab) and examined sensitization of the MPM cell lines to cisplatin-induced by the TRAIL-receptor antibodies. We found that sensitivity of MPM cells to TRAIL, Mapatumumab and Lexatumumab varies largely and is independent of TRAIL-receptor expression. TRAIL-R2 contributes more than TRAIL-R1 to death-receptor mediated apoptosis in MPM cells that express both receptors. The combination of cisplatin with Mapatumumab or Lexatumumab synergistically inhibited the cell growth and enhanced apoptotic death. Furthermore, pre-treatment with cisplatin followed by Mapatumumab or Lexatumumab resulted in significant higher cytotoxic effects as compared to the reverse sequence. Combination-induced cell growth inhibition was significantly abrogated by pre-treatment of the cells with the antioxidant N-acetylcysteine.

CONCLUSION: Our results suggest that the sequential administration of cisplatin followed by Mapatumumab or Lexatumumab deserves investigation in the treatment of patients with MPM.}, } @article {pmid17951344, year = {2007}, author = {Cherrie, JW and Cowie, HA and Jones, AD}, title = {Modelling mesothelioma risk for workers assembling military gas masks.}, journal = {Occupational and environmental medicine}, volume = {64}, number = {11}, pages = {785-6; author reply 785-6}, pmid = {17951344}, issn = {1470-7926}, mesh = {Adult ; Aged ; Asbestos, Crocidolite/*toxicity ; Causality ; Female ; Humans ; Male ; Mesothelioma/etiology/*mortality ; Middle Aged ; Military Personnel ; Models, Statistical ; Occupational Diseases/etiology/mortality ; Occupational Exposure/adverse effects ; Peritoneal Neoplasms/etiology/*mortality ; Pleural Neoplasms/etiology/*mortality ; Respiratory Protective Devices ; Risk Assessment/methods ; Risk Factors ; World War II ; }, } @article {pmid17938727, year = {2007}, author = {Ferrante, D and Bertolotti, M and Todesco, A and Mirabelli, D and Terracini, B and Magnani, C}, title = {Cancer mortality and incidence of mesothelioma in a cohort of wives of asbestos workers in Casale Monferrato, Italy.}, journal = {Environmental health perspectives}, volume = {115}, number = {10}, pages = {1401-1405}, pmid = {17938727}, issn = {0091-6765}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Cohort Studies ; Environmental Exposure/*adverse effects ; Female ; Humans ; Incidence ; Italy/epidemiology ; Lung Neoplasms/*mortality ; Mesothelioma/*mortality ; Middle Aged ; Pleural Neoplasms/*mortality ; Retrospective Studies ; Spouses ; }, abstract = {BACKGROUND: Family members of asbestos workers are at increased risk of malignant mesothelioma (MM). Although the hazard is established, the magnitude of the risk is uncertain, and it is unclear whether risk is also increased for other cancers. Few cohort studies have been reported.

OBJECTIVE: The "Eternit" factory of Casale Monferrato (Italy), active from 1907 to 1986, was among the most important Italian plants producing asbestos-cement (AC) goods. In this article we present updated results on mortality and MM incidence in the wives of workers at the factory.

METHODS: We studied a cohort of 1,780 women, each married to an AC worker during his employment at the factory but not personally occupationally exposed to asbestos. Cohort membership was defined starting from the marital status of each worker, which was ascertained in 1988 from the Registrar's Office in the town where workers lived. At the end of follow-up (April 2003), 67% of women were alive, 32.3% dead, and 0.7% lost to follow-up. Duration of exposure was computed from the husband's period of employment. Latency was the interval from first exposure to the end of follow-up.

RESULTS: The standardized mortality ratio (SMR) for pleural cancer [21 observed vs. 1.2 expected; SMR = 18.00; 95% confidence interval (CI), 11.14-27.52] was significantly increased. Mortality for lung cancer was not increased (12 observed vs. 10.3 expected; SMR = 1.17; 95% CI, 0.60-2.04). Eleven incident cases of pleural MM were observed (standardized incidence ratio = 25.19; 95% CI, 12.57-45.07).

CONCLUSIONS: Household exposure, as experienced by these AC workers' wives, increases risk for pleural MM but not for lung cancer.}, } @article {pmid17915546, year = {2007}, author = {Welch, LS}, title = {Asbestos exposure causes mesothelioma, but not this asbestos exposure: an amicus brief to the Michigan Supreme Court.}, journal = {International journal of occupational and environmental health}, volume = {13}, number = {3}, pages = {318-327}, doi = {10.1179/oeh.2007.13.3.318}, pmid = {17915546}, issn = {1077-3525}, mesh = {Air Pollutants, Occupational/*toxicity ; Asbestos/*toxicity ; Dust ; Humans ; Lung Neoplasms/*chemically induced/epidemiology ; Mesothelioma/*chemically induced/epidemiology ; Michigan ; Motor Vehicles ; Occupational Diseases/*chemically induced/epidemiology ; Occupational Exposure/adverse effects ; *Scientific Misconduct ; }, abstract = {Manufacturers of asbestos brakes, supported by many manufacturing and insurance industry amicus curie, requested the Michigan Supreme Court to dismiss testimony of an expert regarding the ability of asbestos dust from brakes to cause mesothelioma as "junk science". Scientists are concerned with the sweeping and unequivocal claims that any conclusion that asbestos from brakes caused a signature asbestos-related disease in a particular person must be "junk science". The manufacturers' sweeping pronouncements are what veer from accepted, reliable mainstream scientific methods and conclusions. This article outlines the evidence supporting the conclusion that asbestos from brakes can and does cause mesothelioma, and describes the defendants' attempts to fabricate doubt about this conclusion.}, } @article {pmid17909360, year = {2007}, author = {Flores, RM and Zakowski, M and Venkatraman, E and Krug, L and Rosenzweig, K and Dycoco, J and Lee, C and Yeoh, C and Bains, M and Rusch, V}, title = {Prognostic factors in the treatment of malignant pleural mesothelioma at a large tertiary referral center.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {2}, number = {10}, pages = {957-965}, doi = {10.1097/JTO.0b013e31815608d9}, pmid = {17909360}, issn = {1556-1380}, mesh = {Adult ; Aged ; Aged, 80 and over ; Combined Modality Therapy ; Female ; Humans ; Lymphatic Metastasis ; Male ; Mesothelioma/drug therapy/pathology/radiotherapy/*surgery ; Middle Aged ; Neoplasm Staging ; Neoplasms, Glandular and Epithelial/pathology/surgery ; Outcome Assessment, Health Care ; Pleural Neoplasms/drug therapy/pathology/radiotherapy/*surgery ; Prognosis ; Remission Induction ; Smoking ; Survival Rate ; Treatment Outcome ; }, abstract = {INTRODUCTION: Most studies describing the natural history and prognostic factors for malignant pleural mesothelioma antedate accurate pathologic diagnosis, staging by computed tomography, and a universal staging system. We conducted a large single-institution analysis to identify prognostic factors and assess the association of resection with outcome in a contemporary patient population.

METHODS: Patients with biopsy-proven malignant pleural mesothelioma at our institution were identified and clinical data were obtained from an institutional database. Survival and prognostic factors were analyzed by the Kaplan-Meier method, log-rank test, and Cox proportional hazards analysis. A p value <0.05 was considered statistically significant.

RESULTS: From 1990 to 2005, 945 patients were identified: 755 men, 190 women; median age, 66 years (range, 26-93). Extrapleural pneumonectomy was performed in 208 (22%), pleurectomy/decortication in 176 (19%). Operative mortality was 4% (16/384). Multimodality therapy including surgery was associated with a median survival of 20.1 months. Significant predictors of overall survival included histology, gender, smoking, asbestos exposure, laterality, surgical resection by extrapleural pneumonectomy or pleurectomy/decortication, American Joint Committee on Cancer stage, and symptoms. A Cox model demonstrated a hazard ratio of 1.4 without surgical resection when controlling for histology, stage, gender, asbestos exposure, smoking history, symptoms, and laterality (p = 0.003).

CONCLUSIONS: In addition to tumor histology and pathologic stage, predictors of survival include gender, asbestos exposure, smoking, symptoms, laterality, and clinical stage. Surgical resection in a multimodality setting was associated with improved survival.}, } @article {pmid17908991, year = {2007}, author = {Sartore-Bianchi, A and Gasparri, F and Galvani, A and Nici, L and Darnowski, JW and Barbone, D and Fennell, DA and Gaudino, G and Porta, C and Mutti, L}, title = {Bortezomib inhibits nuclear factor-kappaB dependent survival and has potent in vivo activity in mesothelioma.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {13}, number = {19}, pages = {5942-5951}, doi = {10.1158/1078-0432.CCR-07-0536}, pmid = {17908991}, issn = {1078-0432}, mesh = {Animals ; Antineoplastic Agents/pharmacology ; Boronic Acids/*pharmacology ; Bortezomib ; Cell Line, Tumor ; Cell Survival ; Cell Transformation, Neoplastic ; Enzyme Inhibitors/pharmacology ; Humans ; Male ; Mesothelioma/*drug therapy/*metabolism ; Mice ; Mice, Nude ; NF-kappa B/*metabolism ; Nitriles/pharmacology ; Proteasome Inhibitors ; Pyrazines/*pharmacology ; Sulfones/pharmacology ; Tumor Necrosis Factor-alpha/metabolism ; }, abstract = {PURPOSE: Purpose of this study has been the assessment of nuclear factor-kappaB (NF-kappaB) as a survival factor in human mesothelial cells (HMC), transformed HMC and malignant mesothelioma (MMe) cells. We aimed at verifying whether the proteasome inhibitor Bortezomib could abrogate NF-kappaB activity in MMe cells, leading to tumor cell death and may be established as a novel treatment for this aggressive neoplasm.

EXPERIMENTAL DESIGN: In HMC and MMe cells, NF-kappaB nuclear translocation and DNA binding were studied by electrophoretic mobility shift assay, following treatment with tumor necrosis factor-alpha (TNF-alpha). The IKK inhibitor Bay11-7082 was also tested to evaluate its effects on HMC, transformed HMC, and MMe cell viability upon exposure to asbestos fibers. Following Bortezomib treatment, cytotoxicity of MMe cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, whereas apoptosis and cell-cycle blockade were investigated by high-content analysis. Bortezomib was also given to mice bearing i.p. xenografts of MMe cells, and its effects on tumor growth were evaluated.

RESULTS: Here, we show that NF-kappaB activity is a constitutive survival factor in transformed HMC, MMe cells, and acts as a survival factor in HMC exposed to asbestos fibers. Bortezomib inhibits NF-kappaB activity in MMe cells and induces cell cycle blockade and apoptosis in vitro as well as tumor growth inhibition in vivo.

CONCLUSIONS: Inhibition of NF-kappaB constitutive activation in MMe cells by Bortezomib resulted in in vitro cytotoxicity along with apoptosis and in vivo tumor regression. Our results support the use of Bortezomib in the treatment of MMe and has led to a phase II clinical trial currently enrolling in Europe.}, } @article {pmid17907531, year = {2007}, author = {Bianchi, C and Bianchi, T and Tommasi, M}, title = {[Mesothelioma of the pleura in the Province of Trieste].}, journal = {La Medicina del lavoro}, volume = {98}, number = {5}, pages = {374-380}, pmid = {17907531}, issn = {0025-7818}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Biopsy ; Female ; Humans ; Incidence ; Italy/epidemiology ; Male ; Mesothelioma/diagnosis/*epidemiology/pathology ; Middle Aged ; Occupational Exposure ; Occupations ; Pleura/pathology ; Pleural Neoplasms/diagnosis/*epidemiology/pathology ; Risk Factors ; }, abstract = {BACKGROUND: The Province of Trieste, north-eastern Italy (population about 240,000), has been identified as an area with a high incidence of pleural mesothelioma.

OBJECTIVES: (i) To obtain preliminary data on the trend of the mesothelioma epidemic in the Province of Trieste during the last six years; (ii) to define the cases in terms of asbestos exposure.

METHODS: Pleural mesotheliomas diagnosed at the Department of Surgery, Thoracic Surgery Unit, Trieste University, in the period January 2001-May 2006 were reviewed. The histological diagnosis was generally based on material obtained at thoracoscopy, pleurectomy, or pleuropneumonectomy. In three cases the pathological diagnosis was made by biopsy of the thoracic wall, and in a further three cases by cytological examination ofpleuralfluid. Detailed occupational histories were obtained from the patients themselves at the time of first admission.

RESULTS: The group included 99 people resident in the Province of Trieste (89 men and 10 women, aged between 43 and 89 years). On the basis of the occupational history, 95 cases were defined as asbestos-related. A majority ofpatients had been employed in marine work, including shipbuilding (46 cases), port activity (13 cases), and maritime trades (8 cases). Thirteen patients had worked in other industries (iron industry, petrochemical, etc.). Fourteen people had been employed in a variety of occupations (fire-fighter, lift mechanic, cinema projectionist, pastry worker, telephone technician, etc.). Five women had histories of exposure to asbestos at home. About 70% of the patients had their first exposure to asbestos before 1960. Two-thirds of the cases were exposed to asbestos for 20 years or more. Latency periods (time intervals elapsed between first exposure to asbestos and diagnosis of mesothelioma) rangedfrom 25 to 71 years (mean 49.3, median 49.0). One patient had a history ofprior thoracic irradiationfor Hodgkin's disease.

CONCLUSIONS: In the Province of Trieste the mesothelioma epidemic does not show any signs of abatement. Besides marine work, a variety of other occupations appear to be associated with the tumour in this area.}, } @article {pmid17904414, year = {2008}, author = {Ugolini, D and Neri, M and Ceppi, M and Cesario, A and Dianzani, I and Filiberti, R and Gemignani, F and Landi, S and Magnani, C and Mutti, L and Puntoni, R and Bonassi, S}, title = {Genetic susceptibility to malignant mesothelioma and exposure to asbestos: the influence of the familial factor.}, journal = {Mutation research}, volume = {658}, number = {3}, pages = {162-171}, doi = {10.1016/j.mrrev.2007.08.001}, pmid = {17904414}, issn = {0027-5107}, mesh = {Asbestos/*adverse effects ; Disease Outbreaks ; Environmental Exposure/adverse effects ; Family ; Family Health ; *Genetic Predisposition to Disease ; Humans ; Italy/epidemiology ; Mesothelioma/epidemiology/*etiology/*genetics ; Neoplasms/genetics ; }, abstract = {BACKGROUND: Asbestos is the principal etiological factor of malignant mesothelioma (MM), accounting for more than 80% of all tumor cases. However, other co-factors, including genetic susceptibility may play a role in the etiology of this disease, possibly modulating the effects of exposure to asbestos and other carcinogenic mineral fibers. The frequent report of familial clustering was the first indication supporting the involvement of genetic factors. Therefore, we performed an extensive literature search to evaluate existing studies reporting familial cases of MM.

METHODS: Published reports addressing the issue of familial susceptibility to MM have been searched through PubMed using keywords and free text tools. Eighty-two citations were retrieved and 20 of them actually reported a familial cluster of MM. Three more articles were identified through the references. The probability that the observed familial clusters of mesothelioma could have randomly occurred in exposed families was evaluated with the Family History Score Zi (FHSi).

RESULTS: The result of this analysis suggested that clustering of MM cases in families exposed to asbestos may be explained with the additional contribution of other familial factors. The FHSi allowed to reject the hypothesis of random occurrence of these clusters with a probability of a first type error ranging between 1 per cent and 1 per billion.

CONCLUSIONS: The evaluation of the published materials supports the hypothesis that - although familial clustering of MM is largely attributable to shared asbestos exposure - the additional contribution of factors dealing with genetic susceptibility may play a role in the etiology of MM.}, } @article {pmid17895892, year = {2007}, author = {Pira, E and Pelucchi, C and Piolatto, PG and Negri, E and Discalzi, G and La Vecchia, C}, title = {First and subsequent asbestos exposures in relation to mesothelioma and lung cancer mortality.}, journal = {British journal of cancer}, volume = {97}, number = {9}, pages = {1300-1304}, pmid = {17895892}, issn = {0007-0920}, mesh = {Adult ; Asbestos/*adverse effects ; Cohort Studies ; Female ; Humans ; Italy/epidemiology ; Lung Neoplasms/etiology/*mortality ; Male ; Mesothelioma/etiology/*mortality ; Occupational Diseases/etiology/*mortality ; Occupational Exposure ; Peritoneal Neoplasms/etiology/mortality ; Pleural Neoplasms/etiology/mortality ; Survival Rate ; Time Factors ; }, abstract = {We analysed data from a cohort of 1966 subjects (889 men and 1,077 women) employed by an Italian asbestos (mainly textile) company in the period 1946-1984, who were followed-up to 2004. A total of 62,025 person-years of observation were recorded. We computed standardised mortality ratios (SMR) for all causes and selected cancer sites using national death rates for each 5-year calendar period and age group. There were 68 deaths from mesothelioma (25 men and 43 women, 39 pleural and 29 peritoneal) vs 1.6 expected (SMR=4,159), and 109 from lung cancer vs 35.1 expected (SMR=310). The SMRs of pleural/peritoneal cancer were 6661 for subjects exposed only before 30 years of age, 8,019 for those first exposed before 30 and still employed at 30-39 years of age and 5,786 for those first exposed before 30 and still employed at 40 or more years of age. The corresponding SMRs for lung cancer were 227, 446 and 562. The SMR of mesothelioma was strongly related to time since first exposure. The SMR of lung cancer, but not of mesothelioma, appeared to be related to subsequent exposures.}, } @article {pmid17881470, year = {2007}, author = {Krstev, S and Stewart, P and Rusiecki, J and Blair, A}, title = {Mortality among shipyard Coast Guard workers: a retrospective cohort study.}, journal = {Occupational and environmental medicine}, volume = {64}, number = {10}, pages = {651-658}, pmid = {17881470}, issn = {1470-7926}, support = {//Intramural NIH HHS/United States ; }, mesh = {Adult ; Aged ; Baltimore/epidemiology ; Cardiovascular Diseases/mortality ; Causality ; Cohort Studies ; Employment/statistics & numerical data ; Female ; Humans ; Male ; Middle Aged ; Military Personnel/*statistics & numerical data ; Neoplasms/mortality ; Occupational Diseases/*mortality ; Occupational Exposure/statistics & numerical data ; Racial Groups/statistics & numerical data ; Respiratory Tract Diseases/mortality ; Retrospective Studies ; Sex Distribution ; *Ships ; }, abstract = {BACKGROUND: The mortality experience of 4702 (4413 men and 289 women) civilian workers in a US Coast Guard shipyard was evaluated.

METHODS: All workers employed at the shipyard between 1 January 1950 and 31 December 1964 were included in the study and were followed through 31 December 2001 for vital status. Detailed shipyard and lifetime work histories found in the shipyard personnel records and job descriptions were evaluated. Workers were classified as likely exposed to any potential hazardous substances. In addition, 20 job groups were created on likely similar exposures. Standardised mortality ratios (SMRs) were calculated based on the general population of the state and adjusted for age, calendar period, sex and race.

RESULTS: The follow-up was successful for 93.3% of the workers. Among all men employed in the shipyard, there was an excess of mortality from all causes of death (SMR 1.08; 95% CI 1.04 to 1.12), respiratory cancers (SMR 1.29; 95% CI 1.15 to 1.43), lung cancer (SMR 1.26; 95% CI 1.12 to 1.41), mesothelioma (SMR 5.07; 95% CI 1.85 to 11.03) and emphysema (SMR 1.44; 95% CI 1.01 to 1.99) and a decrease for cardiovascular diseases (OR 0.95; 95% CI 0.90 to 1.00), vascular lesions of the central nervous system (SMR 0.80; 95% CI 0.67 to 0.96), cirrhosis of the liver (SMR 0.38; 95% CI 0.25 to 0.57) and external causes of death (SMR 0.55; 95% CI 0.44 to 0.68). A similar pattern was observed for the men classified as exposed. No increasing trend of mortality was found with duration of employment in the shipyard, with the exception of mesothelioma (SMRs of 4.23 and 6.27 for <10 years and > or =10 years, respectively). In occupations with at least three cases and with an SMR of > or =1.3, the authors observed a significantly elevated mortality for lung cancer among machinists (SMR 1.60; 95% CI 1.08 to 2.29) and shipfitters, welders and cutters (SMR 1.34; 95% CI 1.07 to 1.65) and for oral and nasopharyngeal cancers among wood workers (SMR 6.20; 95% CI 2.27 to 13.50).

CONCLUSION: Employment in this Coast Guard shipyard revealed a small but significant excess mortality from all causes, lung cancer and mesothelioma, most of which is probably related to asbestos exposure.}, } @article {pmid17875683, year = {2007}, author = {Comar, M and Rizzardi, C and de Zotti, R and Melato, M and Bovenzi, M and Butel, JS and Campello, C}, title = {SV40 multiple tissue infection and asbestos exposure in a hyperendemic area for malignant mesothelioma.}, journal = {Cancer research}, volume = {67}, number = {18}, pages = {8456-8459}, doi = {10.1158/0008-5472.CAN-07-2232}, pmid = {17875683}, issn = {0008-5472}, support = {CA104818/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; *Cocarcinogenesis ; DNA, Viral/genetics ; Endemic Diseases ; Female ; Humans ; Male ; Mesothelioma/epidemiology/*etiology/virology ; Middle Aged ; Pleural Neoplasms/epidemiology/*etiology/virology ; Polymerase Chain Reaction ; Polyomavirus Infections/*complications/virology ; Retrospective Studies ; Simian virus 40/*genetics ; Tumor Virus Infections/*complications/virology ; }, abstract = {To assess the presence of SV40 in malignant mesothelioma tissue, 19 formalin-fixed paraffin-embedded pleural cancer samples of patients from a hyperendemic area of northeastern Italy were analyzed retrospectively. A total of 48 other tissues from the malignant mesothelioma subjects were investigated. The SV40 load was determined by real-time quantitative PCR. Exposure to asbestos was evaluated through a careful review of the occupational history of patients, supplemented by histology and isolation of asbestos bodies. Three of 19 (15.8%) malignant mesothelioma tissues harbored SV40 genomic signals. Two patients with SV40-positive malignant mesothelioma had viral sequences in another tissue. Overall, 3 of 18 (16.7%) normal liver tissues tested positive for SV40, as did 1 of 8 (12.5%) kidney tissues. SV40 viral loads were higher in malignant mesothelioma than in normal cells (P = 0.045). This survey shows that SV40 sustains infections in multiple tissues in malignant mesothelioma patients from a geographic area affected with asbestos-related mesothelioma.}, } @article {pmid17802734, year = {2007}, author = {Kobayashi, K}, title = {[Relief measure for health issues due to asbestos exposure].}, journal = {Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine}, volume = {96}, number = {8}, pages = {1777-1781}, doi = {10.2169/naika.96.1777}, pmid = {17802734}, issn = {0021-5384}, mesh = {Asbestos/*adverse effects ; *Asbestosis/diagnosis/etiology ; Compensation and Redress/legislation & jurisprudence ; Delivery of Health Care/*legislation & jurisprudence ; Humans ; Japan ; *Lung Neoplasms/diagnosis/etiology ; *Mesothelioma/diagnosis/etiology ; }, } @article {pmid17785560, year = {2007}, author = {Cristaudo, A and Foddis, R and Vivaldi, A and Guglielmi, G and Dipalma, N and Filiberti, R and Neri, M and Ceppi, M and Paganuzzi, M and Ivaldi, GP and Mencoboni, M and Canessa, PA and Ambrosino, N and Chella, A and Mutti, L and Puntoni, R}, title = {Clinical significance of serum mesothelin in patients with mesothelioma and lung cancer.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {13}, number = {17}, pages = {5076-5081}, doi = {10.1158/1078-0432.CCR-07-0629}, pmid = {17785560}, issn = {1078-0432}, mesh = {Aged ; Female ; GPI-Linked Proteins ; Humans ; Lung Neoplasms/*blood/mortality ; Male ; Membrane Glycoproteins/*blood ; Mesothelin ; Mesothelioma/*blood/mortality ; Middle Aged ; Prognosis ; Respiratory Tract Diseases/blood ; }, abstract = {PURPOSE: High levels of serum-soluble mesothelin family proteins (SMRP) have been found to be associated with malignant mesothelioma (MM), but not lung cancer (LC). To verify the clinical role of this marker for both these tumors, we tested serum SMRP in the largest population of thoracic cancers ever assembled.

EXPERIMENTAL DESIGN: SMRP blood concentrations were measured in 107 patients with MM, 215 patients with LC, 130 patients with benign respiratory diseases (BRD), and 262 controls. Statistical comparison between mean serum SMRP levels in all groups was done and receiver operating characteristic curves were constructed to evaluate the performance of this marker.

RESULTS: SMRP levels were significantly higher in patients with MM and LC than in patients with benign respiratory diseases and controls (P < 0.001). The area under the receiver operating characteristic curve for serum SMRP discriminating MM and controls was 0.77 (95% confidence interval, 0.71-0.83), with a best cutoff of 1.00 nmol/L (sensitivity, 68.2%; specificity, 80.5%). In both MM and LC, serum SMRP levels did not differ significantly between early and late stages. High SMRP levels proved to be an independent negative prognostic factor in patients with MM.

CONCLUSIONS: Our data confirm that serum SMRP is a promising marker for the diagnosis, prognosis, and clinical monitoring of MM. We found that serum SMRP dosage may prove helpful in LC diagnosis as well. These data may also have positive repercussions on secondary preventive medical strategies for workers previously exposed to asbestos.}, } @article {pmid17764616, year = {2007}, author = {Otsuki, T and Maeda, M and Murakami, S and Hayashi, H and Miura, Y and Kusaka, M and Nakano, T and Fukuoka, K and Kishimoto, T and Hyodoh, F and Ueki, A and Nishimura, Y}, title = {Immunological effects of silica and asbestos.}, journal = {Cellular & molecular immunology}, volume = {4}, number = {4}, pages = {261-268}, pmid = {17764616}, issn = {1672-7681}, mesh = {Animals ; Antigens, CD/immunology ; Asbestos/*immunology ; Autoantibodies/immunology ; Humans ; Silicon Dioxide/*immunology ; Silicosis/immunology ; T-Lymphocytes, Regulatory/immunology ; }, abstract = {Silicosis patients (SILs) and patients who have been exposed to asbestos develop not only respiratory diseases but also certain immunological disorders. In particular, SIL sometimes complicates autoimmune diseases such as systemic scleroderma, rheumatoid arthritis (known as Caplan syndrome), and systemic lupus erythematoses. In addition, malignant complications such as lung cancer and malignant mesothelioma often occur in patients exposed to asbestos, and may be involved in the reduction of tumor immunity. Although silica-induced disorders of autoimmunity have been explained as adjuvant-type effects of silica, more precise analyses are needed and should reflect the recent progress in immunomolecular findings. A brief summary of our investigations related to the immunological effects of silica/asbestos is presented. Recent advances in immunomolecular studies led to detailed analyses of the immunological effects of asbestos and silica. Both affect immuno-competent cells and these effects may be associated with the pathophysiological development of complications in silicosis and asbestos-exposed patients such as the occurrence of autoimmune disorders and malignant tumors, respectively. In addition, immunological analyses may lead to the development of new clinical tools for the modification of the pathophysiological aspects of diseases such as the regulation of autoimmunity or tumor immunity using cell-mediated therapies, various cytokines, and molecule-targeting therapies. In particular, as the incidence of asbestos-related malignancies is increasing and such malignancies have been a medical and social problem since the summer of 2005 in Japan, efforts should be focused on developing a cure for these diseases to eliminate nationwide anxiety.}, } @article {pmid17723954, year = {2007}, author = {You, B and Blandin, S and Gérinière, L and Lasset, C and Souquet, PJ}, title = {[Family mesotheliomas: genetic interaction with environmental carcinogenic exposure?].}, journal = {Bulletin du cancer}, volume = {94}, number = {7}, pages = {705-710}, pmid = {17723954}, issn = {1769-6917}, mesh = {Aged ; Chromosome Aberrations ; *Environmental Exposure ; Genes, Tumor Suppressor ; Genetic Predisposition to Disease/*genetics ; Humans ; Male ; Mesothelioma/*genetics ; Pleural Neoplasms/*genetics ; *Siblings ; }, abstract = {Our patient was refered to hospital for a malignant mesthelioma 22 years after the prior diagnosis of a mesothelioma in his brother. Their family history included others cancers. No exposure to asbestos was documented in brother's history. Literature is rich with family mesothelioma reports. Most of them are linked to an occupationnal asbestos exposure. But, some studies suggest that family genetic factors are involved in the development of mesothelioma: (genetically transmitted mesotheliomas in Turkish families in Cappadoce, family clustering of cancers including mesotheliomas, inhibition of tumor suppressor genes (INK4A, p53, Nf2...), a small proportion of mesothelioma among asbestosis exposed workers. Many studies suggest an interaction between genetic and environment. A genetic predisposition could lead to an increased susceptibility to carcinogenic factors.}, } @article {pmid17723186, year = {2007}, author = {Zou, H and Luo, SQ and Yang, CY and Zhang, MB}, title = {[Burden of major cancers on years of life lost with premature death in crocidolite-contaminated area in Dayao].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {25}, number = {6}, pages = {326-330}, pmid = {17723186}, issn = {1001-9391}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asbestos, Crocidolite/*adverse effects ; Child ; Child, Preschool ; China/epidemiology ; Cost of Illness ; *Environmental Exposure ; Environmental Pollution/*adverse effects ; Female ; Humans ; Infant ; Life Expectancy ; Male ; Middle Aged ; Neoplasms/*mortality ; Young Adult ; }, abstract = {OBJECTIVE: To evaluate the effects of environmental low-dose exposure to crocidolite on people's health and the society. METHODS The mortality data of cancer between 1994 and 2003 in an environmental crocidolite-contaminated area was obtained from hospital medical records of Dayao Center for Disease Prevention and Control, and Dayao Public Health Bureau. The years of life lost with premature death (YLLs), was used to measure and assess the death, health losses and social burden of cancer in this area.

RESULTS: In the environmental crocidolite-contaminated area, lung cancer was the prime cause of death in all kinds of cancers between 1994 and 2003, followed by liver cancer, mesothelioma stomach cancer and colorectal cancer, with mortality 10.15/10(5), 9.04/10(5), 8.48/10(5), 3.96/10(5) and 3.55/10(5) respectively. The mortality of main cancer in male and female increased with age growing except that of breast cancer in female. Results showed that the types of leading cancers of YLLs were liver cancer, lung cancer, mesothelioma, leukemia and stomach cancer with YLLs 1981.39 person-year, 1886.63 person-year, 1799.23 person-year, 948.01 person-year and 754.18 person-year respectively. The distribution of YLLs was similar in both sexes, higher in the middle age group (aged from 15 to 44 years and 45 to 59 years) and lower in other age groups. The indirect economic loss resulting from lung cancer (15.02% of the total loss), liver cancer (13.98% of the total loss) and mesothelioma (13.01% of the total loss) was relatively great. The YLLs and the indirect economic loss attributable to environmental low-dose exposure to crocidolite were 3092.23 person-year and 5,175,800 Yuan respectively.

CONCLUSION: Lung cancer, liver cancer, mesothelioma, leukemia and breast cancer are the major cancers with an important impact on people's health and premature mortality in the environmental crocidolite-contaminated area. The impact of cancer mortality is more severer in those aged over 45 years. Social burden of cancer is the greatest in persons aged from 15 to 59 years. Policies and plans should be worked out for the protection of environment and the prevention of cancer.}, } @article {pmid17718182, year = {2007}, author = {Brophy, JT and Keith, MM and Schieman, J}, title = {Canada's asbestos legacy at home and abroad.}, journal = {International journal of occupational and environmental health}, volume = {13}, number = {2}, pages = {236-243}, doi = {10.1179/oeh.2007.13.2.236}, pmid = {17718182}, issn = {1077-3525}, mesh = {Air Pollutants/toxicity ; Asbestos/*economics/*toxicity ; Canada ; Commerce ; Developing Countries ; Environmental Exposure/adverse effects ; Extraction and Processing Industry/*economics/organization & administration ; Humans ; Inhalation Exposure/adverse effects ; International Cooperation ; Labor Unions ; Lung Neoplasms/*chemically induced/*epidemiology ; Mesothelioma/*epidemiology ; }, abstract = {Despite international efforts to block Canada's export of asbestos, the Canadian federal government continues to defend the economic interests of the asbestos industry. Ironically, Canadian asbestos miners, mill workers, and those engaged in a wide range of other occupations continue to suffer asbestos-related disease and premature death. Although there is an employer-funded compensation system in each province, many workers with mesothelioma and other asbestos-related diseases remain uncompensated. The export of Canadian asbestos to developing countries sets the stage for another preventable occupational disease epidemic that will manifest over the coming decades. There is growing support from the Canadian labor movement for an end to asbestos exportation and for a just transition strategy for the asbestos workers and their communities.}, } @article {pmid17717621, year = {2007}, author = {Hyland, RA and Ware, S and Johnson, AR and Yates, DH}, title = {Incidence trends and gender differences in malignant mesothelioma in New South Wales, Australia.}, journal = {Scandinavian journal of work, environment & health}, volume = {33}, number = {4}, pages = {286-292}, doi = {10.5271/sjweh.1145}, pmid = {17717621}, issn = {0355-3140}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Female ; Humans ; Male ; Mesothelioma/*epidemiology/physiopathology ; Middle Aged ; New South Wales/epidemiology ; Occupational Diseases/epidemiology ; Occupational Exposure/adverse effects ; Pleural Neoplasms/*epidemiology/physiopathology ; Registries ; Sex Factors ; }, abstract = {OBJECTIVES: Features of malignant mesothelioma reportedly differ between men and women, including occupational asbestos exposure, histological subtype, and median survival. In this study, incidence trends and clinical features for malignant mesothelioma were compared between genders in New South Wales (NSW), where notification of malignant mesothelioma to the Central Cancer Registry is a statutory requirement.

METHODS: Notifications to the Central Cancer Registry were compared with those to the registry of the NSW Workers' Compensation (Dust Diseases) Board. The latter includes occupational and clinical data.

RESULTS: Of the 3090 cases of malignant mesothelioma reported to the Central Cancer Registry between 1972 and 2004, 456 (15%) were female. Altogether 1995 malignant mesotheliomas were compensated between 1969 and 2004, of which 105 (5%) occurred among women. The incidence increased for both genders by approximately 15-fold. Median survival was similar for the men and women for all of the cases (7 versus 6 months), but was better among the women who received compensation (8.5 versus 10.4 months, P<0.0001). The mean disease latency (42.8 years) increased over the study period (P<0.001).

CONCLUSIONS: In New South Wales over the last 30 years, the total number of malignant mesotheliomas and the number of compensated cases of malignant mesothelioma have risen for both genders. The mean latency is increasing, and increasing numbers of "nonoccupational" cases are being reported. Survival remains poor.}, } @article {pmid17717504, year = {2007}, author = {Takahashi, H and Harada, M and Maehara, S and Kato, H}, title = {Localized malignant mesothelioma of the pleura.}, journal = {Annals of thoracic and cardiovascular surgery : official journal of the Association of Thoracic and Cardiovascular Surgeons of Asia}, volume = {13}, number = {4}, pages = {262-266}, pmid = {17717504}, issn = {1341-1098}, mesh = {Diagnosis, Differential ; Humans ; Male ; Mesothelioma/diagnosis/*pathology ; Middle Aged ; Pleural Neoplasms/diagnosis/*pathology ; }, abstract = {Because malignant mesothelioma is commonly seen as a diffuse neoplasm, a localized tumor is an extremely rare form of presentation. Only 45 cases have been reported, and little is known about their behavior. We report a new case of localized malignant mesothelioma with the microscopic appearance of diffuse malignant mesothelioma, but without any evidence of diffuse spread. A 54-year-old man, a former smoker, with a brief history of asbestos exposure for 3 months, presented with a severe right chest pain and a swelling in the same area. Chest-computed tomography (CT) showed a 4.5 cm extra pleural tumor with a smooth surface, located in the right anterior chest wall, and destruction of the 5th rib. A CT-guided needle biopsy revealed malignant mesothelioma. Detailed examinations revealed a resectable solitary localized mass with no distant metastasis. The patient underwent operation, a tumorectomy, plus a combined resection of the chest wall and part of the right middle lobe. A complete en bloc resection was achieved. Pathology revealed localized malignant mesothelioma, biphasic type. Immunohistochemical findings confirmed the mesothelial feature. Localized malignant mesothelioma should be distinguished from diffuse malignant mesothelioma because of its different biological behavior, and in the former complete resection it is associated with a good prognosis.}, } @article {pmid17704197, year = {2008}, author = {Magnani, C and Ferrante, D and Barone-Adesi, F and Bertolotti, M and Todesco, A and Mirabelli, D and Terracini, B}, title = {Cancer risk after cessation of asbestos exposure: a cohort study of Italian asbestos cement workers.}, journal = {Occupational and environmental medicine}, volume = {65}, number = {3}, pages = {164-170}, doi = {10.1136/oem.2007.032847}, pmid = {17704197}, issn = {1470-7926}, mesh = {Adult ; *Asbestos ; Construction Materials ; Female ; Follow-Up Studies ; Humans ; *Industry ; Italy ; Likelihood Functions ; Lung Neoplasms/mortality ; Male ; Mesothelioma/*mortality ; Middle Aged ; Neoplasms/*mortality ; Occupational Diseases/*mortality ; *Occupational Exposure ; Ovarian Neoplasms/mortality ; Peritoneal Neoplasms/mortality ; Pleural Neoplasms/mortality ; Regression Analysis ; Risk Assessment/methods ; Time Factors ; Uterine Neoplasms/mortality ; }, abstract = {OBJECTIVES: We aimed to study mortality for asbestos related diseases and the incidence of mesothelioma in a cohort of Italian asbestos cement workers after cessation of asbestos exposure.

METHODS: The Eternit factory operated from 1907 to 1986. The cohort included 3434 subjects active in 1950 or hired in 1950-86, ascertained from company records, without selections. Local reference rates were used for both mortality and mesothelioma incidence.

RESULTS: Mortality was increased in both sexes for all causes (overall 1809 observed (obs) vs 1312.3 expected (exp); p<0.01), pleural (135 obs vs 3.6 exp; p<0.01) and peritoneal (52 vs 1.9; p<0.01) malignancies and lung cancer (249 vs 103.1; p<0.01). In women, ovarian (9 vs 4.0; p<0.05) and uterine (15 vs 5.8; p<0.01) malignancies were also in excess. No statistically significant increase was found for laryngeal cancer (16 obs vs 12.2 exp). In Poisson regression analyses, the RR of death from pleural neoplasm linearly increased with duration of exposure, while it showed a curvilinear increase with latency and time since cessation of exposure. RR for peritoneal neoplasm continued to increase by latency, duration and time since cessation of exposure. RR for lung cancer showed a reduction after 15 years since cessation of exposure and levelled off after 40 years of latency.

CONCLUSION: This study of a cohort of asbestos exposed workers with very long follow-up confirmed the reduction in risk of death from lung cancer after the end of exposure. It also suggested a reduction in risk for pleural mesothelioma with over 40 years of latency, while risk for peritoneal mesothelioma showed a continuing increase.}, } @article {pmid17702624, year = {2008}, author = {Fassina, A and Fedeli, U and Corradin, M and Da Frè, M and Fabbris, L}, title = {Accuracy and reproducibility of pleural effusion cytology.}, journal = {Legal medicine (Tokyo, Japan)}, volume = {10}, number = {1}, pages = {20-25}, doi = {10.1016/j.legalmed.2007.06.001}, pmid = {17702624}, issn = {1344-6223}, mesh = {Adult ; Aged ; Aged, 80 and over ; Compensation and Redress ; Female ; Forensic Pathology ; Humans ; Immunohistochemistry ; Male ; Mesothelioma/*diagnosis ; Middle Aged ; Neoplasm Metastasis/*diagnosis ; Observer Variation ; Pleural Effusion/*pathology ; Pleural Neoplasms/*diagnosis ; Predictive Value of Tests ; Reproducibility of Results ; Sensitivity and Specificity ; }, abstract = {The increasing number of Malignant Mesothelioma (MM) cases that arrive for expert examinations to court for compensation reasons in subjects exposed to asbestos, in many instances rely exclusively on cytological smears of pleural effusion. We evaluated the accuracy and reproducibility of cytological pleural effusions, based on morphological criteria alone. Nine pathologists and eight residents from seven institutions in north-east Italy blindly examined 45 smears of MM (17), metastases (14) and benign effusions (14), in two rounds. Diagnoses had been confirmed by immunohistochemical and clinical follow-up, and eventually at autopsy. Diagnostic accuracy, interobserver and intraobserver agreement in the distinction of benign vs malignant cases, and in the differentiation of primary from metastatic malignancies, were evaluated. The distinction of benign from malignant smears resulted rather satisfactory (k=0.514), but markedly decreased in differentiation of MM from metastases (overall agreement: k=0.343), as well as when readings from residents were analyzed (k=0.132). Cytology is a useful and reliable tool in the identification of malignancies, but when the distinction of primary from metastatic tumors is addressed morphological criteria alone are not sufficient for a definite diagnosis of MM and the use of cell blocks, immunohistochemistry (IHC) and molecular ancillary techniques are recommended.}, } @article {pmid17695086, year = {2007}, author = {Pugnaloni, A and Lucarini, G and GiantomassI, F and Lombardo, L and Capella, S and Belluso, E and Zizzi, A and Panico, AM and Biagini, G and Cardile, V}, title = {In vitro study of biofunctional indicators after exposure to asbestos-like fluoro-edenite fibres.}, journal = {Cellular and molecular biology (Noisy-le-Grand, France)}, volume = {53 Suppl}, number = {}, pages = {OL965-80}, pmid = {17695086}, issn = {1165-158X}, mesh = {Actins/metabolism ; Animals ; Asbestos, Amphibole/metabolism/*toxicity ; Cell Line ; Cell Line, Tumor ; Cell Movement/drug effects ; Cell Survival/drug effects ; Cyclooxygenase 2/analysis/metabolism ; Dinoprostone/analysis ; Epithelial Cells/drug effects/metabolism ; Formazans/metabolism ; Humans ; Immunohistochemistry ; In Vitro Techniques ; Lung/cytology/*drug effects/metabolism ; Macrophages/drug effects/metabolism ; Mesothelioma/metabolism ; Mice ; Mineral Fibers ; Tetrazolium Salts/metabolism ; Vascular Endothelial Growth Factor A/biosynthesis ; beta Catenin/biosynthesis ; }, abstract = {The in vitro biological response to fluoro-edenite (FE) fibres, an asbestos-like amphibole, was evaluated in lung alveolar epithelial A549, mesothelial MeT-5A and monocyte-macrophage J774 cell lines. The mineral has been found in the vicinity of the town of Biancavilla (Catania, Sicily), where an abnormal incidence of mesothelioma has been documented. Cell motility, distribution of polymerized actin, and synthesis of vascular endothelial growth factor (VEGF) and of beta-catenin, critical parameters for tumour development, progression and survival, were investigated in A549 and MeT-5A cells exposed to 50 microg/ml FE fibres for 24 hr and 48 hr. The levels of cyclooxygenase (COX-2) and prostaglandin (PGE2), two molecules involved in cancer pathogenesis by affecting mitogenesis, cell adhesion, immune surveillance and apoptosis, were measured in J774 cells treated with FE fibres under the same experimental conditions. Finally, FE fibres were studied by SEM and EDS analysis to investigate their chemical composition. Exposure of A549 and MeT-5A cells to FE fibres affected differentially phalloidin-stained cytoplasmic F-actin networks, cell motility and VEGF and beta-catenin expression according to the different sensitivity of the two cell lines. In J774 cells it induced a significant increase in COX-2 expression, as assessed by Western blot analysis, and in the concentration of PGE2, measured in culture media by ELISA. SEM-EDS investigations demonstrated two types of FE fibres, edenite and fluoro-edenite, differing in chemical composition and both recognizable as calcic amphiboles. Fibre width ranged from less than 1 microm (prevalently 0.5 microm) to 2-3 microm (edenite) up to several microm (fluoro-edenite); length ranged from about 6 to 80 microm (edenite) up to some hundred microm (fluoro-edenite). Results provide convincing evidence that FE fibres are capable of inducing in vitro functional modifications in a number of parameters with crucial roles in cancer development and progression. Inhaled FE fibres have the potential to induce mesothelioma, even though their ability to penetrate lung alveoli depends on their aerodynamic diameter.}, } @article {pmid17690532, year = {2008}, author = {Matanoski, GM and Tonascia, JA and Correa-Villaseñor, A and Yates, KC and Fink, N and Elliott, E and Sanders, B and Lantry, D}, title = {Cancer risks and low-level radiation in U.S. shipyard workers.}, journal = {Journal of radiation research}, volume = {49}, number = {1}, pages = {83-91}, doi = {10.1269/jrr.06082}, pmid = {17690532}, issn = {0449-3060}, mesh = {Adult ; Dose-Response Relationship, Radiation ; Follow-Up Studies ; Gamma Rays/*adverse effects ; Humans ; Industry/statistics & numerical data ; Male ; Neoplasms/*etiology/*mortality ; Neoplasms, Radiation-Induced/*mortality ; *Nuclear Reactors/statistics & numerical data ; Occupational Exposure/*adverse effects/statistics & numerical data ; Risk Assessment ; Risk Factors ; Time ; United States ; }, abstract = {The risks for four cancers, leukemia, lymphopoietic cancers (LHC), lung cancer and mesothelioma, were studied in workers from shipyards involved in nuclear powered ship overhauls. The population represented a sample of all workers based on radiation dose at study termination. The final sample included 28,000 workers with > or = 5.0 mSv, 10,462 workers with < 5.0 mSv and 33,353 non-nuclear workers. Nuclear workers had lower mortality rates for leukemia and LHC than US white males but higher rates of lung cancer and a significant five-fold excess of mesothelioma. Dose-dependent analyses of risks in the high exposure group indicated that for each cancer the risk increased at exposures above 10.0 mSv. An internal comparison of workers with 50.0 mSv exposures to workers with exposures of 5.0-9.9 mSv indicated relative risks for leukemia of 2.41 (95% CI: 0.5, 23.8), for LHC, 2.94 (95% CI: 1.0,12.0), for lung cancer, 1.26 (95% CI: 0.9, 1.9) and for mesothelioma, 1.61 (95% CI: 0.4, 9.7) for the higher exposure group. Except for LHC, these risks are not significant. However, the increasing risk with increasing exposure for these cancers, some of which are known to be related to radiation, suggests that low-level protracted exposures to gamma rays may be associated with these cancers. Other agents such as asbestos, which are common to shipyard work, may play a role especially in the risk of mesothelioma. Future follow up of the population would identify bounds on radiation risks for this population for comparison with similar risks estimated from other populations.}, } @article {pmid17679279, year = {2007}, author = {Davis, C}, title = {Fatal legacy of asbestos.}, journal = {Nursing standard (Royal College of Nursing (Great Britain) : 1987)}, volume = {21}, number = {42}, pages = {24-25}, doi = {10.7748/ns.21.42.24.s27}, pmid = {17679279}, issn = {0029-6570}, mesh = {Asbestos/*toxicity ; Humans ; Mesothelioma/*chemically induced/mortality/nursing ; Nurse's Role ; Occupational Health ; United Kingdom/epidemiology ; }, abstract = {Mesothelioma is a fatal disease with no cure. Thousands have contracted it unwittingly through their job, environment or those they live with.}, } @article {pmid17675318, year = {2008}, author = {Mak, V and Davies, E and Putcha, V and Choodari-Oskooei, B and Møller, H}, title = {The epidemiology and treatment of mesothelioma in South East England 1985-2002.}, journal = {Thorax}, volume = {63}, number = {2}, pages = {160-166}, doi = {10.1136/thx.2006.066886}, pmid = {17675318}, issn = {1468-3296}, support = {MC_EX_G0800814/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adolescent ; Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Combined Modality Therapy ; England/epidemiology ; Female ; Humans ; Incidence ; Infant ; Male ; Mesothelioma/*epidemiology/therapy ; Middle Aged ; Respiratory Tract Neoplasms/*epidemiology/therapy ; Sex Distribution ; Survival Analysis ; }, abstract = {OBJECTIVES: To describe trends in the incidence of mesothelioma for men and women in South East England and the geographical variation at the level of primary care trust. To describe treatment patterns by cancer network of residence, and relative survival by cancer network, disease stage and treatment modality.

METHODS: 5753 cases were extracted from the Thames Cancer Registry database. We calculated age standardised incidence rates for each year, age specific incidence rates in 10 year age groups, and we used linear regression to compute the average annual percentage change in age standardised incidence. We used Poisson regression to analyse generational trends in incidence.

RESULTS: Men had five times higher incidence of mesothelioma than women. In men, there was an overall 4% increase per year between 1985 and 2002. Over the same period, the overall increase in incidence for women was 5% per year. The incidence was highest in men aged over 70 years, and men aged over 80 years had the highest increase of 8% per year. The incidence rate ratio increased for men born between 1892 and 1942 and started to slow for those born from 1947 onwards. Areas along the Thames and its estuary had the highest incidence. There was some variation by cancer network in the proportion of patients receiving cancer surgery, radiotherapy and chemotherapy. There were no discernable differences in relative survival by cancer network of residence or disease stage but those receiving combined treatment had higher 5 year survival.

CONCLUSIONS: Mesothelioma incidence has increased in South East England, particularly for men aged over 70 years. The highest incidence occurs along the Thames and its estuary, reflecting areas of asbestos use in shipbuilding and industry in the past. More research is needed to understand the interrelationships of prognostic factors, treatment choices and survival, and to determine the best care and support for these patients and their families.}, } @article {pmid17663051, year = {2007}, author = {Liubchenko, PN and Viatkina, EI and Dubrova, SE}, title = {[Case of asbestosis with massive benign pleural involvement].}, journal = {Meditsina truda i promyshlennaia ekologiia}, volume = {}, number = {4}, pages = {35-39}, pmid = {17663051}, issn = {1026-9428}, mesh = {Aged ; Asbestosis/*diagnosis/diagnostic imaging/pathology ; Female ; Humans ; Pleural Diseases/*diagnosis/diagnostic imaging/pathology ; Thoracoscopy/*methods ; Tomography, X-Ray Computed ; }, abstract = {UNLABELLED: The article contains a case of asbestosis in woman aged 65 and long exposed to asbestos at work. X-ray signs proved asbestosis of lungs. Nodular masses in pleura revealed on pulmonary CT scans were considered as malignant mesothelioma. For diagnosis verification, videothoracoscopy with target biopsy of the nodes was performed. Histologic diagnosis - fragments of dense fibrous connective tissue.

FINAL DIAGNOSIS: Asbestosis, s/s, p/p, 2/2. Pleural asbestosis. The authors stress importance of contemporary diagnostic techniques in occupational pathology.}, } @article {pmid17659810, year = {2007}, author = {Tsou, JA and Galler, JS and Wali, A and Ye, W and Siegmund, KD and Groshen, S and Laird, PW and Turla, S and Koss, MN and Pass, HI and Laird-Offringa, IA}, title = {DNA methylation profile of 28 potential marker loci in malignant mesothelioma.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {58}, number = {2}, pages = {220-230}, pmid = {17659810}, issn = {0169-5002}, support = {P30 CA014089/CA/NCI NIH HHS/United States ; P30 CA014089-349012/CA/NCI NIH HHS/United States ; P30 CA 14089/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*genetics ; Cluster Analysis ; *DNA Methylation ; Female ; Humans ; Kaplan-Meier Estimate ; Male ; Mesothelioma/*genetics ; Middle Aged ; Neoplasm Proteins/genetics ; }, abstract = {Patients with malignant mesothelioma (MM), an aggressive cancer associated with asbestos exposure, usually present clinically with advanced disease and this greatly reduces the likelihood of curative treatment. MM is difficult to diagnose without invasive techniques; the development of non-invasively detectable molecular markers would therefore be highly beneficial. DNA methylation changes in cancer cells provide powerful markers that are potentially detectable non-invasively in DNA shed into bodily fluids. Here we examined the methylation status of 28 loci in 52 MM tumors to investigate their potential as molecular markers for MM. To exclude candidate MM markers that might be positive in biopsies/pleural fluid due to contaminating surrounding non-tumor lung tissue/DNA, we also examined the methylation of these markers in lung samples (age- or environmentally induced hypermethylation is frequently observed in non-cancerous lung). Statistically significantly increased methylation in MM versus non-tumor lung samples was found for estrogen receptor 1 (ESR1; p = 0.0002), solute carrier family 6 member 20 (SLC6A20; p = 0.0022) and spleen tyrosine kinase (SYK; p=0.0003). Examination of associations between methylation levels of the 28 loci and clinical parameters suggest associations of the methylation status of metallothionein genes with gender, histology, asbestos exposure, and lymph node involvement, and the methylation status of leucine zipper tumor suppressor 1 (LZTS1) and SLC6A20 with survival.}, } @article {pmid17646232, year = {2007}, author = {Creaney, J and van Bruggen, I and Hof, M and Segal, A and Musk, AW and de Klerk, N and Horick, N and Skates, SJ and Robinson, BW}, title = {Combined CA125 and mesothelin levels for the diagnosis of malignant mesothelioma.}, journal = {Chest}, volume = {132}, number = {4}, pages = {1239-1246}, doi = {10.1378/chest.07-0013}, pmid = {17646232}, issn = {0012-3692}, mesh = {Aged ; Biomarkers, Tumor/*blood/metabolism ; CA-125 Antigen/*blood/metabolism ; Female ; GPI-Linked Proteins ; Humans ; Immunohistochemistry ; Male ; Membrane Glycoproteins/*blood/metabolism ; Mesothelin ; Mesothelioma/*diagnosis ; Middle Aged ; ROC Curve ; Sensitivity and Specificity ; Tissue Distribution ; }, abstract = {BACKGROUND: Malignant mesothelioma is an aggressive, uniformly fatal tumor. Serum markers would be useful for the diagnosis of this disease. One potential marker is mesothelin. The purpose of this study was to study the mesothelin biomarker in a large patient cohort and to determine if another biomarker, CA125, improves on the sensitivity of mesothelin in the diagnosis of mesothelioma.

METHODS: Serum levels of mesothelin and CA125 were determined by commercially available assays in 117 samples obtained at diagnosis from patients with pleural malignant mesothelioma, 33 healthy, asbestos-exposed individuals, 53 patients with asbestos-related lung or pleural disease, and 30 patients presenting with benign pleural effusions. Cross-validated sensitivities were determined, and receiver operator characteristic curves were generated to compare the diagnostic accuracy of the biomarkers.

RESULTS: CA125 had a cross-validated sensitivity of 27% for mesothelioma patients at a specificity of 95% relative to asbestos-exposed individuals, or 50% relative to individuals with benign pleural effusions. Mesothelin had a cross-validated sensitivity of 52% for mesothelioma patients, at a sensitivity of 95% relative to individuals with benign lung or pleural disease. CA125 and mesothelin levels were discordant in > 50% of mesothelioma patients. Combining the data from the two biomarkers using a logistic regression model did not improve sensitivity for detecting mesothelioma above that of the mesothelin marker alone.

CONCLUSION: Combining mesothelin and CA125 data does not improve the sensitivity of mesothelioma diagnosis over mesothelin alone. The use of both markers potentially increases the number of patients who can be monitored.}, } @article {pmid17637924, year = {2007}, author = {Maule, MM and Magnani, C and Dalmasso, P and Mirabelli, D and Merletti, F and Biggeri, A}, title = {Modeling mesothelioma risk associated with environmental asbestos exposure.}, journal = {Environmental health perspectives}, volume = {115}, number = {7}, pages = {1066-1071}, pmid = {17637924}, issn = {0091-6765}, mesh = {Asbestos/*toxicity ; Case-Control Studies ; *Environmental Exposure ; Humans ; Mesothelioma/*chemically induced ; *Models, Theoretical ; Risk Assessment ; }, abstract = {BACKGROUND: Environmental asbestos pollution can cause malignant mesothelioma, but few studies have involved dose-response analyses with detailed information on occupational, domestic, and environmental exposures.

OBJECTIVES: In the present study, we examined the spatial variation of mesothelioma risk in an area with high levels of asbestos pollution from an industrial plant, adjusting for occupational and domestic exposures.

METHODS: This population-based case-control study included 103 incident cases of mesothelioma and 272 controls in 1987-1993 in the area around Casale Monferrato, Italy, where an important asbestos cement plant had been active for decades. Information collected included lifelong occupational and residential histories. Mesothelioma risk was estimated through logistic regression and a mixed additive-multiplicative model in which an additive scale was assumed for the risk associated with both residential distance from the plant and occupational exposures. The adjusted excess risk gradient by residential distance was modeled as an exponential decay with a threshold.

RESULTS: Residents at the location of the asbestos cement factory had a relative risk for mesothelioma of 10.5 [95% confidence interval (CI), 3.8-50.1), adjusted for occupational and domestic exposures. Risk decreased rapidly with increasing distance from the factory, but at 10-km the risk was still 60% of its value at the source. The relative risk for occupational exposure was 6.0 (95% CI, 2.9-13.0), but this increased to 27.5 (95% CI, 7.8-153.4) when adjusted for residential distance.

CONCLUSIONS: This study provides strong evidence that asbestos pollution from an industrial source greatly increases mesothelioma risk. Furthermore, relative risks from occupational exposure were underestimated and were markedly increased when adjusted for residential distance.}, } @article {pmid17634686, year = {2007}, author = {Bianchi, C and Bianchi, T}, title = {Malignant mesothelioma: global incidence and relationship with asbestos.}, journal = {Industrial health}, volume = {45}, number = {3}, pages = {379-387}, doi = {10.2486/indhealth.45.379}, pmid = {17634686}, issn = {0019-8366}, mesh = {Asbestos/*toxicity ; Developed Countries/*statistics & numerical data ; Environmental Exposure/*adverse effects ; *Global Health ; Humans ; Incidence ; Mesothelioma/*epidemiology/etiology ; Risk Factors ; }, abstract = {Mesothelioma incidence varies markedly from one country to another. The highest annual crude incidence rates (about 30 cases per million) are observed in Australia, Belgium, and Great Britain. A lot of data indicate a relationship between mesothelioma and asbestos. The hot areas for mesothelioma exactly correspond to the sites of industries with high asbestos use, such as shipbuilding and asbestos-cement industry. However, in many countries with high asbestos consumption, mesothelioma incidence is low. The reasons for this fact are not clear. The latency periods elapsing between first exposure to asbestos and development of mesothelioma are mostly longer than 40 yr. An inverse relationship exists between intensity of asbestos exposure and length of the latency period. Mesothelioma generally develops after long-time exposures to asbestos. Some recent studies show that the risk increases with the duration of exposure. Possible co-factors in the pathogenesis of asbestos-related mesothelioma include genetic predisposition, diets poor in fruit and vegetables, viruses, immune impairment, recurrent serosal inflammation. The study of co-morbidity in mesothelioma could give an insight into the pathogenesis of the tumor. While a levelling-off in mesothelioma incidence has been registered in some countries, a worsening of the epidemic is predictable in large parts of the world.}, } @article {pmid17632429, year = {2007}, author = {Frija, J and Fournier, M}, title = {[Asbestos in France].}, journal = {Revue des maladies respiratoires}, volume = {24}, number = {6}, pages = {687-689}, doi = {10.1016/s0761-8425(07)91144-4}, pmid = {17632429}, issn = {0761-8425}, mesh = {Asbestos/adverse effects ; *Asbestosis/complications/diagnosis/economics ; Carcinogens ; France ; Humans ; Legislation as Topic ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Workers' Compensation/economics/legislation & jurisprudence ; }, } @article {pmid17625219, year = {2007}, author = {Kauppinen, T and Saalo, A and Pukkala, E and Virtanen, S and Karjalainen, A and Vuorela, R}, title = {Evaluation of a national register on occupational exposure to carcinogens: effectiveness in the prevention of occupational cancer, and cancer risks among the exposed workers.}, journal = {The Annals of occupational hygiene}, volume = {51}, number = {5}, pages = {463-470}, doi = {10.1093/annhyg/mem030}, pmid = {17625219}, issn = {0003-4878}, mesh = {Carcinogens/*toxicity ; Finland/epidemiology ; Government Publications as Topic ; Humans ; Neoplasms/chemically induced/epidemiology/*prevention & control ; Occupational Diseases/chemically induced/epidemiology/*prevention & control ; Occupational Exposure/*adverse effects ; Registries/*standards ; Risk Factors ; Workplace/standards ; }, abstract = {OBJECTIVES: The objective of this study was to evaluate the performance and effectiveness of a register of employees exposed to carcinogens (the ASA Register) which has been in operation in Finland since 1979, and to study cancer risks among the notified workers.

METHODS: The impact of ASA at workplaces was studied by questionnaires mailed to 1448 work departments, which were notified to ASA in 1996, and to 1033 departments, which departed ASA in 1991-1996. The mailing was responded by 69% of departments. The cancer incidence of 35,138 workers notified to ASA in 1979-1988 was followed up through the files of the Finnish Cancer Register for the period 1980-2003.

RESULTS: Changes eliminating or substantially reducing exposure to carcinogens were reported by 73% of departments notified to ASA in 1996. The ASA notification process had directly prompted measures to reduce exposure (8% of cases) or contributed to them (24% of cases). Estimations based on responses of the workplaces suggested that the ASA registration had decreased exposure of 600 workers year(-1) (out of approximately 15,000 notified workers, which is <1% of the employed in Finland), preventing thereby an unknown number of occupational cancers. Other benefits of ASA included the saving of the treatment costs of prevented cancers, the prevention of other health outcomes of carcinogens, improved safety behaviour of exposed workers and avoidance of human suffering among cancer patients and their families. The labour safety authorities had better possibilities to direct their activities against carcinogen exposure. These benefits should be considered against the annual costs, mainly due to 7-8 person-years of work required by tasks related to ASA. The results of the cancer incidence study among notified workers were based on a relatively short follow-up (on average 19 years). The incidence of mesothelioma was significantly increased in the ASA cohort, probably due to exposure to asbestos.

CONCLUSIONS: These results suggest that a national exposure register may stimulate preventive measures at workplaces. Partially based on the results of the present study the Finnish Ministry of Social Affairs and Health continues ASA registration.}, } @article {pmid17620293, year = {2007}, author = {Zanazzi, C and Hersmus, R and Veltman, IM and Gillis, AJ and van Drunen, E and Beverloo, HB and Hegmans, JP and Verweij, M and Lambrecht, BN and Oosterhuis, JW and Looijenga, LH}, title = {Gene expression profiling and gene copy-number changes in malignant mesothelioma cell lines.}, journal = {Genes, chromosomes & cancer}, volume = {46}, number = {10}, pages = {895-908}, doi = {10.1002/gcc.20475}, pmid = {17620293}, issn = {1045-2257}, mesh = {Biomarkers, Tumor/genetics/metabolism ; Blotting, Western ; *Chromosome Aberrations ; Chromosome Mapping ; Chromosomes, Human/*genetics ; Gene Dosage/*genetics ; Gene Expression Profiling/*methods ; Genome, Human/genetics ; Humans ; In Situ Hybridization, Fluorescence ; Mesothelioma/*genetics/metabolism ; Nucleic Acid Hybridization ; Oligonucleotide Array Sequence Analysis/*methods ; Spectral Karyotyping ; Tumor Suppressor Protein p53/genetics/metabolism ; }, abstract = {Malignant mesothelioma (MM) is an asbestos-induced tumor that acquires aneuploid DNA content during the tumorigenic process. We used instable MM cell lines as an in vitro model to study the impact of DNA copy-number changes on gene expression profiling, in the course of their chromosomal redistribution process. Two MM cell lines, PMR-MM2 (early passages of in vitro culture) and PMR-MM7 (both early and late passages of in vitro culture), were cytogenetically characterized. Genomic gains and losses were precisely defined using microarray-based comparative genomic hybridization (array-CGH), and minimal overlapping analysis led to the identification of the common unbalanced genomic regions. Using the U133Plus 2.0 Affymetrix gene chip array, we analyzed PMR-MM7 early and late passages for genome-wide gene expression, and correlated the differentially expressed genes with copy-number changes. The presence of a high number of genetic imbalances occurring from early to late culture steps reflected the tendency of MM cells toward genomic instability. The selection of specific chromosomal abnormalities observed during subsequent cultures demonstrated the spontaneous evolution of the cancer cells in an in vitro environment. MM cell lines were characterized by copy-number changes associated with the TP53 apoptotic pathway already present at the first steps of in vitro culture. Prolonged culture led to acquisition of additional chromosomal copy-number changes associated with dysregulation of genes involved in cell adhesion, regulation of mitotic cell cycle, signal transduction, carbohydrate metabolism, motor activity, glycosaminoglycan biosynthesis, protein binding activity, lipid transport, ATP synthesis, and methyltransferase activity.}, } @article {pmid17610473, year = {2007}, author = {Zekri, AR and Bahnassy, AA and Mohamed, WS and Hassan, N and Abdel-Rahman, AR and El-Kassem, FA and Gaafar, R}, title = {Evaluation of simian virus-40 as a biological prognostic factor in Egyptian patients with malignant pleural mesothelioma.}, journal = {Pathology international}, volume = {57}, number = {8}, pages = {493-501}, doi = {10.1111/j.1440-1827.2007.02130.x}, pmid = {17610473}, issn = {1320-5463}, mesh = {Adult ; Asbestos/poisoning ; DNA, Viral/analysis ; Egypt/epidemiology ; Environmental Exposure/adverse effects ; Female ; Fluorescent Antibody Technique, Indirect ; Gene Expression Regulation, Neoplastic ; Humans ; Male ; Mesothelioma/mortality/pathology/*virology ; Middle Aged ; Pleural Neoplasms/mortality/pathology/*virology ; Polyomavirus Infections/pathology/*virology ; Prognosis ; Prospective Studies ; Retinoblastoma Protein/metabolism ; Simian virus 40/genetics/*isolation & purification ; Survival Rate ; Tumor Suppressor Protein p53/genetics/metabolism ; Tumor Virus Infections/pathology/*virology ; }, abstract = {The association between simian virus (SV40) and malignant pleural mesothelioma (MPM) suggests an etiological role for SV40. However, exact pathogenetic mechanisms and possible prognostic value are not clear. The purpose of the present paper was to investigate 40 Egyptian MPM patients for the presence of SV40 DNA, altered Rb expression and p53 gene status using immunohistochemistry and molecular techniques. The relation between SV40, asbestos exposure, Rb, p53 and their contribution to the overall survival (OS) were also assessed. SV40 DNA was detected in 20/40 patients and asbestos exposure in 31 patients; 18 of them were SV40 positive. Altered p53 and Rb expression were detected in 57.5% and 52.5%, respectively, with no p53 mutation. Univariate analysis showed a significant correlation between OS and stage (P = 0.03), performance status (P = 0.04), p53 overexpression (P = 0.05), asbestos exposure (P = 0.002) and SV40 (P = 0.001). Multivariate analysis showed that when SV40 and asbestos exposure were considered together, only combined positivity of both was an independent prognostic factor affecting the OS (P = 0.001). SV40 and asbestos exposure are common in Egyptian MPM, denoting a possible etiological role and a synergistic effect for both agents. Combined positivity for SV40 and asbestos exposure is an independent prognostic factor in MPM, having a detrimental effect on OS.}, } @article {pmid17608064, year = {2006}, author = {Omura, Y and Shimotsuura, Y and Duvvi, H and Ohata, N and Ohki, M}, title = {Reduced glucose uptake with markedly increased gastrin releasing peptide, osteopontine & asbestos found in dark black areas of PET Scan of chest wall in patient with mesothelioma.}, journal = {Acupuncture & electro-therapeutics research}, volume = {31}, number = {3-4}, pages = {247-257}, doi = {10.3727/036012906815844256}, pmid = {17608064}, issn = {0360-1293}, mesh = {Aged ; Asbestos/*metabolism ; Fluorodeoxyglucose F18/*pharmacokinetics ; Gastrin-Releasing Peptide/*metabolism ; Humans ; Lung Neoplasms/diagnostic imaging/*metabolism ; Male ; Mesothelioma/diagnostic imaging/*metabolism ; Osteopontin/*metabolism ; Positron-Emission Tomography/methods ; Radiopharmaceuticals/pharmacokinetics ; Thorax/diagnostic imaging/metabolism ; }, abstract = {PET Scans are most often used for detecting cancer and other malignant tumors because for most of them, glucose uptake is higher than in normal tissues. However, in mesothelioma, our study showed excessive deposits of Asbestos of 0.5 mg BDORT units, and markedly reduced Glucose uptake of less than 1/30 of normal tissue. As a consequence, the authors found that, in the location where there is a mesothelioma, distinctive dark black areas much darker than any normal tissue appear in the PET Scan. Therefore, a PET Scan taken parallel to the front & back of the chest wall often shows pitch-black areas on the chest wall of the patient, located on the ribs in the case of large black areas and between the ribs in the case of small black areas. If the amount of Asbestos in these areas is found to be very high in the same location where the glucose uptake is very low, one can suspect the presence of mesothelioma, which is often found at the inner wall of the chest cavity or the peritoneum in the abdomen with significantly increased Osteopontine (about 350-400 times that of normal tissue) and very significant increase in Gastrin Releasing Peptides (more than 1200 times that of normal tissue). In some patients, the only abnormal blood chemistry detected was abnormally increased Pro-Gastrin Releasing Peptide. This dark black area on the PET Scan image taken parallel to front and back of chest wall (with marked increase in asbestos, Gastrin-Releasing Peptide, & Osteopontine and marked decrease in glucose uptake in the pathological tissue) can be considered a characteristic finding for the diagnosis of mesothelioma.}, } @article {pmid19727362, year = {2007}, author = {Bishay, A and Raoof, S and Esan, A and Sung, A and Wali, S and Lee, LY and George, L and Saleh, A and Baumann, M}, title = {Update on pleural diseases--2007.}, journal = {Annals of thoracic medicine}, volume = {2}, number = {3}, pages = {128-142}, pmid = {19727362}, issn = {1817-1737}, abstract = {BACKGROUND: New information is available on pleural diseases. The authors selected articles to make recommendations on diagnostic and treatment aspects of pleural diseases.

MATERIALS AND METHODS: Eleven articles published in the English language between 2004 and 2007 were chosen. The basis of selection of the articles was the impact on daily practice, change in prior thinking of a disease process or specific treatment modality, as well as proper design and execution of the study. 5-Amino-laevulinic acid with fluorescent light combined with white light may allow further diagnostic yield in undiagnosed pleural disease. FDG-PET may allow prognostication of patients with pleural tumors. Utilizing ultrasound by trained Emergency Department physicians is a rapid and effective technique to evaluate non-traumatic pleural effusions in symptomatic patients. Serum osteopontin levels may distinguish patients exposed to asbestos with benign disease from those with pleural mesothelioma. Administration of streptokinase in patients with empyema does not need for surgical drainage, length of hospital stay, or mortality as compared to conventional treatment with chest tube drainage and intravenous antibiotics. Silver nitrate may be an alternative agent to talc for producing pleurodesis. Routine use of graded talc (50% particles greater than 25 microns) is recommended to reduce the morbidity associated with talc pleurodesis. Study design does not permit us to conclude that aspiration of spontaneous pneumothorax is as effective as chest tube drainage. Pleural catheter may prove to be an important palliative modality in treating debilitated patients or patients with trapped lung who show symptomatic improvement with drainage; however, at the present time, these catheters cannot be considered a first line treatment option for patients with malignant pleural effusion. One of the studies reviewed showed no significant difference in tract metastasis in patients with malignant mesothelioma undergoing an invasive pleural procedure with or without irradiation to the procedure site. However, the design of the trial does not allow us to make this conclusion at the present time.}, } @article {pmid17598352, year = {2007}, author = {Sacco, A and Magnavita, N}, title = {[Adenocarcinoma of the colon, professional exposure to asbestos and family history of pleural mesothelioma].}, journal = {La Medicina del lavoro}, volume = {98}, number = {3}, pages = {252-254}, pmid = {17598352}, issn = {0025-7818}, mesh = {Adenocarcinoma/epidemiology/*etiology ; Aged ; Asbestos/*adverse effects ; Case-Control Studies ; Causality ; Cohort Studies ; Colonic Neoplasms/epidemiology/*etiology ; Humans ; Male ; Mesothelioma/genetics ; Occupational Exposure ; Pleural Neoplasms/genetics ; Siblings ; Smoke/adverse effects ; *Welding ; }, } @article {pmid17598349, year = {2007}, author = {Canti, Z and Scillia, R and Cantoni, S and Mensi, C}, title = {[Malignant mesothelioma of the pleura in a truck driver].}, journal = {La Medicina del lavoro}, volume = {98}, number = {3}, pages = {216-220}, pmid = {17598349}, issn = {0025-7818}, mesh = {Aged ; Asbestos/*adverse effects ; *Automobile Driving ; Causality ; Equipment Contamination ; Fatal Outcome ; Humans ; Male ; Mesothelioma/*etiology ; Mineral Fibers/*adverse effects ; *Motor Vehicles ; Occupational Diseases/*etiology ; Occupational Exposure ; Pleural Neoplasms/*etiology ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Among the responsibilities of the health operators in the occupational health and safety services of the local health units in Lombardy (Italy) is the administration of standardized questionnaires for the investigation of possible occupational exposure to asbestos fibres in subjects diagnosed with malignant mesothelioma.

OBJECTIVES: To describe a case of malignant mesothelioma in a truck driver suspected of being occupationally exposed to asbestos during the course of administration of the questionnaire.

METHODS: Analysis of the literature regarding asbestos contamination of truck cabs. Some years ago Italian authors described a case of asbestosis in a truck-driver and findings of pollution by asbestos fibres in the cabs of some models of trucks.

RESULTS: The subject had worked for more than 30 years as a truck driver operating on long distances on truck models described in literature as contaminated by asbestos fibres. He had not transported materials made of asbestos, and had not carried out maintenance on the trucks, nor had he any non-occupational sources of exposure to asbestos. Thus the mesothelioma was related to occupational exposure and procedures were initiated for reporting a suspected occupational disease.}, } @article {pmid17590095, year = {2007}, author = {Ponce Lorenzo, J and Giménez Ortiz, A and Aparisi Aparisi, F and Fleitas Kanonnikoff, T and Montalar Salcedo, J}, title = {[Peritoneal mesothelioma: an inusual clinical presentation in a patient without exposure to asbestos].}, journal = {Anales de medicina interna (Madrid, Spain : 1984)}, volume = {24}, number = {2}, pages = {81-83}, doi = {10.4321/s0212-71992007000200008}, pmid = {17590095}, issn = {0212-7199}, mesh = {Asbestos ; Fatal Outcome ; Humans ; Male ; Mesothelioma/*diagnosis/drug therapy ; Middle Aged ; Peritoneal Neoplasms/*diagnosis/drug therapy ; }, abstract = {Malignant mesothelioma is an insidious neoplasm arising from the mesotelial surfaces, of the pleural and peritoneal cavities, the tunica vaginalis, or the pericardium. The predominant cause is inhalation exposure to asbestos. We present a rare case of primary malignant mesothelioma of the peritoneum in a 64 year old man without history of inhalation exposure to asbestos. The initial symptoms were constitutional syndrome and right pleural effusion. Positron emission tomography combined with computed tomography (PET/TC) was useful for a supporting diagnosis and to determine the extension. The patient received treatment with systemic palliative chemotherapy, cisplatin-pemetrexed. After three cycles, partial response was observed, but the evolution was fatal due to secondary toxicity of chemotherapy.}, } @article {pmid17575406, year = {2007}, author = {Kumagai, S and Kurumatani, N}, title = {[Risk of developing mesothelioma due to neighborhood exposure to asbestos].}, journal = {Sangyo eiseigaku zasshi = Journal of occupational health}, volume = {49}, number = {3}, pages = {77-88}, doi = {10.1539/sangyoeisei.49.77}, pmid = {17575406}, issn = {1341-0725}, mesh = {*Asbestos ; *Environmental Exposure ; Humans ; Mesothelioma/*etiology ; }, abstract = {Routes of asbestos exposure consist of occupational and non-occupational exposures, and furthermore the latter is classified as para-occupational, neighborhood or true general environmental exposure. Consequently, in order to evaluate health risk caused by neighborhood exposure to asbestos, it is necessary to exclude risk due to the other exposure routes from overall risk. We reviewed epidemiological studies on the relationship between neighborhood asbestos exposure and risk of mesothelioma. In studies on a crocidolite mine in South Africa and a chrysotile mine in Canada, occupational exposure was not excluded. In studies on a crocidolite mine in Australia and an asbestos manufacturing factory in U.S.A., risk caused by non-occupational exposure was evaluated, but the risk was not classified as para-occupational and neighborhood exposures. In a study on an asbestos cement factory in Italy, first, occupational and para-occupational exposures were excluded, and next, the incidence rate of mesothelioma in neighborhood residents was calculated, so that risk caused by neighborhood exposure could be evaluated. In case-control studies in Italy, South Africa, three European countries and the U.K., risks caused by occupational, para-occupational and neighborhood exposures were evaluated separately. As a whole, relative risk (RR) of neighborhood exposure in crocidolite and amosite mines was about 10 to 30 and RR in major asbestos factories was about 5 to 20. On the other hand, statistically significant RR of neighborhood exposure was not observed in chrysotile mines and some asbestos facilities.}, } @article {pmid17573841, year = {2009}, author = {Gogou, E and Kerenidi, T and Chamos, V and Zintzaras, E and Gourgoulianis, KI}, title = {Mesothelioma mortality in Greece from 1983 to 2003.}, journal = {International journal of clinical practice}, volume = {63}, number = {6}, pages = {944-948}, doi = {10.1111/j.1742-1241.2007.01334.x}, pmid = {17573841}, issn = {1742-1241}, mesh = {Cause of Death/trends ; Female ; Greece/epidemiology ; Humans ; Incidence ; Male ; Mesothelioma/*mortality ; Occupational Diseases/*mortality ; Residence Characteristics ; Retrospective Studies ; Sex Distribution ; }, abstract = {OBJECTIVE: To present summary statistics of the Greek mesothelioma epidemic including summaries by occupation and geographical area.

METHODS: The National Statistics Service provides our data, which contain all deaths from 1983 to 2003 where mesothelioma was mentioned on the death certificate.

RESULTS: The annual number of mesothelioma deaths has increased from 9 in the 3-year period of time 1983-1985 to 53 in 2001-2003. Current deaths in males account for about 72% of the cases. The area of Epirus in Greece has the highest cause-specific mortality rate over the period 1983-2003. The occupational group which is related to the higher number of mesothelioma deaths was clerks and those occupied in business; following farmers, workers-technicians and drivers.

CONCLUSION: Our data suggest a change in the balance of risk away from traditional asbestos exposure industries to industries where one could describe the exposure as secondary such as plumbers, technicians, drivers, farmers. Also, we found out that the higher cause-specific mortality rate was 0.38/100,000 population in Epirus, the lower was 0.025/100,000 in Thessalia and the national average rate was 0.10/100,000 population.}, } @article {pmid17573637, year = {2007}, author = {Borelli, V and Brochetta, C and Melato, M and Rizzardi, C and Polentarutti, M and Busatto, C and Vita, F and Abbate, R and Gotter, R and Zabucchi, G}, title = {A procedure for the isolation of asbestos bodies from lung tissue by exploiting their magnetic properties: a new approach to asbestos body study.}, journal = {Journal of toxicology and environmental health. Part A}, volume = {70}, number = {14}, pages = {1232-1240}, doi = {10.1080/15287390701380906}, pmid = {17573637}, issn = {1528-7394}, mesh = {Asbestos/*analysis/*toxicity ; Asbestosis/pathology ; DNA Breaks, Single-Stranded ; Humans ; In Vitro Techniques ; Lung/*chemistry ; Lung Neoplasms/pathology ; *Magnetics ; Mesothelioma/pathology ; Microscopy, Electron, Scanning ; Neutrophils/drug effects ; }, abstract = {The role of asbestos bodies (and associated proteinacious coating) in asbestos associated diseases is not well understood. Currently employed methods of isolation of these bodies employ harsh chemicals that lead to destruction of their proteinacious coating. In this work a method was developed that enabled the purification of whole, integral, unmodified asbestos bodies (AB) by exploiting their magnetic properties. Albumin and ferritin were found to be the major proteins associated with AB isolated from lung tissue of mesothelioma patients. Magnetically isolated AB were shown to be cytotoxic and to activate free radical production from inflammatory cells at a higher extent than that induced by bodies obtained by chemical digestion. The finding that hypochlorite-treated AB induce DNA damage, while AB obtained by the method described in this article failed to do so, together with the differential behavior of these bodies toward inflammatory cells, suggests that native asbestos bodies should be used to investigate the pathogenetic role of these structures.}, } @article {pmid17567726, year = {2007}, author = {Burdorf, A and Järvholm, B and Siesling, S}, title = {Asbestos exposure and differences in occurrence of peritoneal mesothelioma between men and women across countries.}, journal = {Occupational and environmental medicine}, volume = {64}, number = {12}, pages = {839-842}, pmid = {17567726}, issn = {1470-7926}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Female ; Humans ; Incidence ; Male ; Mesothelioma/epidemiology/*etiology ; Middle Aged ; Netherlands/epidemiology ; Occupational Diseases/epidemiology/*etiology ; Occupational Exposure/*adverse effects ; Peritoneal Neoplasms/epidemiology/*etiology ; Sex Factors ; Sweden/epidemiology ; }, abstract = {OBJECTIVE: In several countries the incidence of peritoneal mesotheliomas among women closely mirrors the pattern among men. The aim was to investigate the role of asbestos exposure in the aetiology of peritoneal mesotheliomas in women and men.

METHODS: All cases of peritoneal mesothelioma were selected from the Swedish and Netherlands Cancer Registers for the period 1989-2003. For both countries incidence rates were calculated and stratified by sex. A linear regression analysis was used to analyse the existence of a trend over time.

RESULTS: Among men the incidence rate of peritoneal mesothelioma in the Netherlands (0.60 per 100 000 persons) was consistently higher than in Sweden with an average ratio of 1.8 (range 1.4-2.8). In both countries no trend over time was observed. During the 15-year period in the Netherlands the incidence rate among men was about 3.3-fold higher than among women. In Sweden the incidence rate among women was slightly higher than in men up to 1999, and thereafter about threefold higher among men. This sudden shift was statistically significant and seemed mainly caused by changes in classification of peritoneal tumours.

CONCLUSION: The absence of a time trend in the incidence rate of peritoneal mesothelioma in the Netherlands and Sweden in the past 15 years may point to a more limited role of occupational exposure to asbestos in the aetiology of peritoneal mesothelioma than for pleural mesothelioma, especially among women. The observed drop around 2000 in annual incidence of peritoneal mesothelioma among Swedish women indicates the presence in the past of a substantial misclassification with other tumours in the peritoneum.}, } @article {pmid17563612, year = {2007}, author = {Beall, C and Corn, M and Cheng, H and Matthews, R and Delzell, E}, title = {Mortality and cancer incidence among tire manufacturing workers hired in or after 1962.}, journal = {Journal of occupational and environmental medicine}, volume = {49}, number = {6}, pages = {680-690}, doi = {10.1097/JOM.0b013e318074bb30}, pmid = {17563612}, issn = {1076-2752}, mesh = {Adult ; Confidence Intervals ; Employment/statistics & numerical data ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Neoplasms/*epidemiology/etiology/mortality ; Occupational Exposure/*adverse effects ; Registries ; *Rubber ; Texas/epidemiology ; }, abstract = {OBJECTIVE: This study evaluated mortality during 1962 through 2003 and cancer incidence during 1995 through 2003 at a tire manufacturing plant.

METHODS: The mortality study included 3425 men and women, employed for at least one year. Of these, 3069 were eligible for the cancer incidence study.

RESULTS: Employees experienced 390 deaths compared with 608 expected (standardized mortality ratio (SMR)=64; 95% confidence interval (CI)=58-71). Total cancer mortality (123 observed, SMR=75, CI=62-89) and lung cancer mortality (47 observed, SMR=72, CI=53-96) were lower than expected. Hourly white men had small increases in stomach cancer, bladder cancer, and leukemia deaths. During 1995 through 2003, 169 incident cancers were observed compared with 197 expected (SIR=86, 95% CI=74-100). Three mesothelioma cases occurred among hourly white men (SIR=653, CI=135-1907); all were exposed potentially to asbestos before starting at the rubber plant.

CONCLUSIONS: Small numbers and limited information on jobs, occupational agents, and lifestyle preclude attribution of observed increases to workplace exposures.}, } @article {pmid17551308, year = {2007}, author = {Deutsch, M and Land, SR and Begovic, M and Cecchini, R and Wolmark, N}, title = {An association between postoperative radiotherapy for primary breast cancer in 11 National Surgical Adjuvant Breast and Bowel Project (NSABP) studies and the subsequent appearance of pleural mesothelioma.}, journal = {American journal of clinical oncology}, volume = {30}, number = {3}, pages = {294-296}, doi = {10.1097/01.coc.0000256102.40842.78}, pmid = {17551308}, issn = {1537-453X}, mesh = {Adult ; Aged ; Breast Neoplasms/*radiotherapy ; Carcinoma, Intraductal, Noninfiltrating/radiotherapy ; Female ; Humans ; Mesothelioma/*etiology ; Middle Aged ; Pleural Neoplasms/*etiology ; Postoperative Period ; Prospective Studies ; Radiation Injuries/*complications ; Radiotherapy, Adjuvant/adverse effects ; }, abstract = {OBJECTIVES: Among the minority of patients with pleural mesothelioma and no known exposure to asbestos, there have been case reports suggesting a possible association with previous radiotherapy. The association between radiotherapy for primary breast cancer and the subsequent occurrence of mesothelioma was investigated in women entered into 11 National Surgical Adjuvant Breast and Bowel Project (NSABP) prospective clinical trials for breast cancer.

METHODS: Follow-up information was obtained on 22,140 patients entered into 11 NSABP clinical trials for treatment of primary breast cancer between 1971 and 1994. Postoperative radiotherapy was administered to 9342 patients, mainly after lumpectomy. Postlumpectomy patients were treated with radiotherapy just to the ipsilateral breast and without regional nodal irradiation. There were 12,798 patients who did not have postoperative radiotherapy, and almost all had mastectomy.

RESULTS: Three pleural mesotheliomas were identified, and all occurred in the ipsilateral thorax of the irradiated patients (P = 0.009). All had received postlumpectomy breast irradiation for ductal carcinoma in situ. None had a known previous exposure to asbestos.

CONCLUSIONS: There appears to be a small but statistically significant increased risk of developing mesothelioma following radiotherapy administered for primary breast cancer. However, in absolute numbers, the risk is too small to be considered a contraindication to administering radiotherapy when indicated.}, } @article {pmid17539854, year = {2007}, author = {Osman, E and Hasan, B and Meral, U and Ercan, A and Mehmet, T and Nazan, B and Ayhan, O and Erhan, E and Oner, D}, title = {Recent discovery of an old disease: malignant pleural mesothelioma in a village in south-east Turkey.}, journal = {Respirology (Carlton, Vic.)}, volume = {12}, number = {3}, pages = {448-451}, doi = {10.1111/j.1440-1843.2006.01027.x}, pmid = {17539854}, issn = {1323-7799}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Asbestos, Amphibole/adverse effects ; Biopsy ; Environmental Exposure/*adverse effects ; Female ; Humans ; Incidence ; Lung/pathology ; Male ; Mesothelioma/diagnostic imaging/*epidemiology/*etiology ; Middle Aged ; Occupational Exposure/adverse effects ; Pleural Neoplasms/diagnostic imaging/*epidemiology/*etiology ; Radiography, Thoracic ; Turkey/epidemiology ; }, abstract = {BACKGROUND AND OBJECTIVE: Environmental asbestos exposure is reportedly common in some districts of Turkey. The aim of this study was to investigate the presence and effect of environmental asbestos exposure in a village in Gaziantep, Turkey, with reported cases of mesothelioma.

METHODS: All villagers > or =14 years old were subject to an interview rediagnosis and a detailed questionnaire. Chest microfilms were performed in all cases, and additional standard CXRs were obtained when necessary. Samples collected from the natural mantle, and whitewash from the houses were analysed for the presence of asbestos.

RESULTS: In total, 269 villagers took part in the study. The incidence of histopathologically diagnosed malignant pleural mesothelioma was 0.32% relative to the total village population in the year 2000. The verbal autopsy revealed eight possible cases of malignant pleural mesothelioma, all of whom had died within the past 12 years. Of these eight, there was a first-degree kinship between three, and additionally, these patients had a third-degree relationship with a biopsy proven case. Radiological evaluation showed pleural calcification and/or thickness in 3.3%, and pleural effusion in 0.4% of patients undergoing CXR. All houses in the village were constructed using adobe soil, and the interior whitewash was made from soil containing asbestos. Analysis of soil samples revealed tremolite and/or actinolyte asbestos.

CONCLUSION: The current findings suggest that environmental asbestos exposure continue to be a serious health concern in the Gaziantep region of Turkey.}, } @article {pmid17534390, year = {2007}, author = {Tsiouris, A and Walesby, RK}, title = {Malignant pleural mesothelioma: current concepts in treatment.}, journal = {Nature clinical practice. Oncology}, volume = {4}, number = {6}, pages = {344-352}, doi = {10.1038/ncponc0839}, pmid = {17534390}, issn = {1743-4262}, mesh = {Animals ; Antineoplastic Agents/*therapeutic use ; Asbestos/adverse effects ; Cisplatin/therapeutic use ; Clinical Trials as Topic ; Combined Modality Therapy ; Glutamates/therapeutic use ; Guanine/analogs & derivatives/therapeutic use ; Humans ; Mesothelioma/*therapy ; Pemetrexed ; Pleural Neoplasms/*therapy ; Radiation Tolerance ; Treatment Outcome ; }, abstract = {Malignant pleural mesothelioma (MPM) is a primary and locally aggressive tumor of the pleura. A well defined causal relationship with asbestos exposure, and an overwhelming media interest in the use of asbestos in industrialized countries after World War II, has produced a high level of awareness of this disease. With a peak incidence of MPM expected in Europe, Australia, and the US within the next 15 years, and the failure of current treatment approaches to offer long-term survival and improve quality of life, new therapeutic regimens are warranted. The effects of surgery in terms of survival and symptomatic relief have yet to be defined because of a lack of randomized trials. The role of radiotherapy in the treatment of MPM remains controversial, as the radiosensitivity of malignant mesothelial cells is modest. MPM response to chemotherapy is comparatively poor. The combination of pemetrexed and cisplatin chemotherapy has achieved the best objective responses. Presently, a multimodal approach is considered to be the cornerstone of treatment of MPM. Important ongoing international and national trials are addressing the roles of chemotherapy (e.g. the EAP and MS01 trial), radical surgery (e.g. the MARS trial) and radiotherapy (e.g. the SAKK group phase III study).}, } @article {pmid17534183, year = {2007}, author = {Scherpereel, A and Lee, YC}, title = {Biomarkers for mesothelioma.}, journal = {Current opinion in pulmonary medicine}, volume = {13}, number = {4}, pages = {339-443}, doi = {10.1097/MCP.0b013e32812144bb}, pmid = {17534183}, issn = {1070-5287}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Biomarkers, Tumor/*metabolism ; Diagnosis, Differential ; Humans ; Mesothelin ; Mesothelioma/diagnosis/*metabolism ; Pleural Neoplasms/diagnosis/*metabolism ; }, abstract = {PURPOSE OF REVIEW: Mesothelioma is an incurable cancer and its global incidence continues to increase. There has been strong interest in the search for a biomarker that would be of value for the diagnosis, prognosis and disease monitoring of mesothelioma. Large series evaluating the use of novel candidate markers have recently been published.

RECENT FINDINGS: To date, global gene profiling studies have failed to find a molecule that reliably captures all subtypes of mesothelioma, and differentiates it from benign pathologies and metastatic carcinomas. Soluble mesothelin-related peptide (SMRP), osteopontin and megakaryocyte potentiating factor have been assessed as markers. SMRP testing is clinically available and provides reasonable diagnostic sensitivity and specificity when applied to serum or pleural fluid. Elevated SMRP levels can occur in metastatic, especially ovarian and pancreatic, adenocarcinomas. False negatives are common with sarcomatoid mesothelioma. SMRP levels may reflect tumor load and disease progression. The role of SMRP in predicting mesothelioma development in subjects exposed to asbestos has raised interest. Osteopontin lacks specificity as a diagnostic marker for mesothelioma but may have value in disease monitoring.

SUMMARY: The proposed markers have insufficient accuracy to replace cytohistology as the gold standard for diagnosis for mesothelioma. Elevated SMRP levels raise suspicion of mesothelioma although negative values do not exclude disease. Its role in disease monitoring in patients and in predicting disease development in at-risk individuals warrant further study.}, } @article {pmid17534182, year = {2007}, author = {Yarborough, CM}, title = {The risk of mesothelioma from exposure to chrysotile asbestos.}, journal = {Current opinion in pulmonary medicine}, volume = {13}, number = {4}, pages = {334-338}, doi = {10.1097/MCP.0b013e328121446c}, pmid = {17534182}, issn = {1070-5287}, mesh = {Asbestos, Serpentine/*adverse effects ; Global Health ; Humans ; Incidence ; Mesothelioma/*chemically induced/epidemiology ; Occupational Diseases/*chemically induced/epidemiology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*chemically induced/epidemiology ; Risk Assessment ; Risk Factors ; Survival Rate ; }, abstract = {PURPOSE OF REVIEW: This review assesses the risk of developing diffuse malignant mesothelioma of the pleura from exposures to chrysotile fibers and contrasts it with the known risk of amphibole asbestos.

RECENT FINDINGS: Although a rare cancer, the mortality rates of pleural mesothelioma continue to be significantly elevated because of past occupational exposures to airborne asbestos fibers. New analyses of occupational epidemiologic studies for highly exposed workers show a substantially lower potency and suggest an empiric threshold for chrysotile compared with amphibole asbestos. Important kinetic and pathological differences between chrysotile and amphiboles have been substantiated that support chrysotile's impotency in causing pleural mesothelioma.

SUMMARY: Excess risk of pleural mesothelioma from past exposures to asbestos, as evidenced by a trend of high incidence rates during the last half century, appears to be the result of nonchrysotile asbestiform fibers. Although scientific efforts and legal arguments continue, the risk of pleural mesothelioma in human populations is probably negligible for exposures to airborne chrysotile asbestos that is not known to be contaminated by amphibole. This distinction for asbestos fiber types is pivotal for understanding hazards and characterizing risks of continued use of natural chrysotile asbestos today and also new nanofibers.}, } @article {pmid17532875, year = {2007}, author = {Hansen, J and Rasmussen, TR and Omland, Ø and Olsen, JH and , }, title = {[Registration of selected cases of occupational cancer (1994-2002) with the Danish National Board of Industrial Injuries].}, journal = {Ugeskrift for laeger}, volume = {169}, number = {18}, pages = {1674-1678}, pmid = {17532875}, issn = {1603-6824}, mesh = {Adenocarcinoma/epidemiology/*etiology ; Adult ; Aged ; Denmark/epidemiology ; Female ; Humans ; Male ; Mandatory Reporting ; Mesothelioma/epidemiology/*etiology ; Middle Aged ; Occupational Diseases/epidemiology/*etiology ; Occupational Exposure/adverse effects ; Paranasal Sinus Neoplasms/epidemiology/*etiology ; Physician's Role ; Pleural Neoplasms/epidemiology/*etiology ; Registries ; }, abstract = {INTRODUCTION: Persons in Denmark afflicted by an occupational disease are offered economical compensation and it is the responsibility of the physician to register such cases with the Danish National Board on Industrial Injuries. However, the number of cancers reported to the Board is lower than expected. We evaluated the causes of underreporting for two types of cancer with a major occupational background.

MATERIALS AND METHODS: Cases of pleural mesothelioma and adenocarcinoma of the sinonasal cavities diagnosed between 1994 and 2002 were drawn from the Danish Cancer Registry. Patients were searched for in the files of the National Board of Industrial Injuries. For patients not registered, information on employment history since 1964 and job title was collected from the Danish Supplementary Pension Fund and the Central Population Register, and the likelihood of occupational exposure to asbestos and wood dust was evaluated.

RESULTS: 695 individuals were registered with pleural mesothelioma and 108 with adenocarcinoma of the sinonasal cavities in the Cancer Registry. Of these, 381 (55%) patients with mesothelioma and 44 (41%) patients with adenocarcinoma were also registered with the National Board of Industrial Injuries. Among the latter, 91% and 87%, respectively were judged by the Board to be occupationally induced. For 3 out of 4 cases not registered with the Board register-based occupational information was available. This information indicated exposure to asbestos by 60% of the men and 3% of the women; the equivalent figures for adenocarcinoma and wood dust were 32% and 0%, respectively.

CONCLUSION: We observed a substantial underreporting of pleural mesothelioma and adenocarcinoma of the sinonasal cavities with the National Board of Industrial Injuries. The underreporting seemed to be unchanged since the 1980s. We propose that all cases of mesothelioma and all cases of cancer of the sinonasal cavities not registered with the Board are referred to a department for industrial medicine for etiological evaluation.}, } @article {pmid17532755, year = {2007}, author = {Okio, H and Kazu, S and Masahiro, M}, title = {Diagnostic biomarker of asbestos-related mesothelioma: example of translational research.}, journal = {Cancer science}, volume = {98}, number = {8}, pages = {1147-1151}, pmid = {17532755}, issn = {1347-9032}, mesh = {Animals ; Asbestos/*toxicity ; Biomarkers, Tumor/*analysis ; Environmental Exposure ; Enzyme-Linked Immunosorbent Assay ; GPI-Linked Proteins ; Lung Neoplasms/*etiology ; Membrane Glycoproteins/*analysis ; Mesothelin ; Mesothelioma/*chemically induced/*etiology ; Oncogene Proteins/*analysis ; Peritoneal Neoplasms/*etiology ; Pleural Neoplasms/*etiology ; Rats ; }, abstract = {Mesothelioma is an aggressive tumor arising from the mesothelium, and is usually associated with previous exposure to asbestos. The incubation period of asbestos-related mesothelioma is estimated to be approximately 30-40 years. Once mesothelioma has occurred, there is no effective treatment. So, identification of tumor markers and a method for early diagnosis using such markers are urgently needed. Recently, several enzyme-linked immunosorbent assay systems for Erc/mesothelin have been developed, the reported usefulness of which has been assessed and demonstrated as a diagnostic tool. Asbestos-related mesothelioma should be ascribed as a typical environmental carcinogen. In this review, we will present asbestos-related mesothelioma for the study of problems in environmental carcinogenesis.}, } @article {pmid17521217, year = {2007}, author = {Goudar, RK}, title = {Management options for malignant pleural mesothelioma: clinical and cost considerations.}, journal = {Drugs}, volume = {67}, number = {8}, pages = {1149-1165}, pmid = {17521217}, issn = {0012-6667}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Combined Modality Therapy ; Genetic Therapy ; Humans ; Mesothelioma/*economics/*therapy ; Palliative Care ; Photochemotherapy ; Pleural Neoplasms/*economics/radiotherapy/*therapy ; Prognosis ; Pulmonary Surgical Procedures ; }, abstract = {Malignant pleural mesothelioma (MPM) is a resistant form of lung cancer that is often related to prior asbestos exposure. While surgical resection and radiotherapy techniques have been refined in recent years, neither has been proven to significantly extend patient survival compared with untreated controls. Until the release of pemetrexed in 2004, even combination chemotherapy regimens often resulted in a response rate of <20%. A recent phase III trial documented a 41.3% response rate for cisplatin plus pemetrexed. In the future, new multimodality regimens featuring novel targeted therapies directed against molecular targets, such as the vascular endothelial growth factor, hold the greatest promise for improved outcomes in MPM. The standard radiographic assessment of response to MPM therapy remains a poor surrogate for clinically relevant endpoints such as median survival. Furthermore, it is not currently known whether aggressive multimodality treatment for MPM will improve survival or quality of life above and beyond symptomatic care. Ongoing clinical trials are comparing chemotherapy and surgery with supportive care in an effort to define the role of different therapies in MPM. MPM treatment is a costly public health issue; after efficacy is proven, additional studies are needed to measure the cost effectiveness of MPM treatment regimens.}, } @article {pmid17512853, year = {2007}, author = {Nawrot, TS and Van Kersschaever, G and Van Eycken, E and Nemery, B}, title = {Belgium: historical champion in asbestos consumption.}, journal = {Lancet (London, England)}, volume = {369}, number = {9574}, pages = {1692}, doi = {10.1016/S0140-6736(07)60776-4}, pmid = {17512853}, issn = {1474-547X}, mesh = {Asbestos/*adverse effects ; Belgium/epidemiology ; Humans ; Male ; Mesothelioma/*etiology/mortality ; }, } @article {pmid17511710, year = {2007}, author = {Cox, LA and Popken, DA}, title = {Some limitations of aggregate exposure metrics.}, journal = {Risk analysis : an official publication of the Society for Risk Analysis}, volume = {27}, number = {2}, pages = {439-445}, doi = {10.1111/j.1539-6924.2007.00896.x}, pmid = {17511710}, issn = {0272-4332}, mesh = {Animals ; Asbestos/toxicity ; California ; *Environmental Exposure ; Hazardous Substances/*toxicity ; Humans ; Risk ; Risk Assessment ; Risk Factors ; Risk Management ; United States ; United States Environmental Protection Agency ; }, abstract = {Aggregate exposure metrics based on sums or weighted averages of component exposures are widely used in risk assessments of complex mixtures, such as asbestos-associated dusts and fibers. Allowed exposure levels based on total particle or fiber counts and estimated ambient concentrations of such mixtures may be used to make costly risk-management decisions intended to protect human health and to remediate hazardous environments. We show that, in general, aggregate exposure information alone may be inherently unable to guide rational risk-management decisions when the components of the mixture differ significantly in potency and when the percentage compositions of the mixture exposures differ significantly across locations. Under these conditions, which are not uncommon in practice, aggregate exposure metrics may be "worse than useless," in that risk-management decisions based on them are less effective than decisions that ignore the aggregate exposure information and select risk-management actions at random. The potential practical significance of these results is illustrated by a case study of 27 exposure scenarios in El Dorado Hills, California, where applying an aggregate unit risk factor (from EPA's IRIS database) to aggregate exposure metrics produces average risk estimates about 25 times greater - and of uncertain predictive validity - compared to risk estimates based on specific components of the mixture that have been hypothesized to pose risks of human lung cancer and mesothelioma.}, } @article {pmid17504993, year = {2007}, author = {Grigoriu, BD and Scherpereel, A and Devos, P and Chahine, B and Letourneux, M and Lebailly, P and Grégoire, M and Porte, H and Copin, MC and Lassalle, P}, title = {Utility of osteopontin and serum mesothelin in malignant pleural mesothelioma diagnosis and prognosis assessment.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {13}, number = {10}, pages = {2928-2935}, doi = {10.1158/1078-0432.CCR-06-2144}, pmid = {17504993}, issn = {1078-0432}, mesh = {Aged ; Extracellular Fluid/chemistry ; Female ; GPI-Linked Proteins ; Humans ; Male ; Membrane Glycoproteins/*blood ; Mesothelin ; Mesothelioma/*diagnosis/mortality ; Middle Aged ; Osteopontin/*blood ; Pleura/chemistry ; Pleural Neoplasms/*diagnosis/mortality ; Prognosis ; Survival Analysis ; }, abstract = {PURPOSE: Malignant mesothelioma is a highly aggressive tumor and is often diagnosed too late for a curative treatment. We compared diagnostic and prognostic values of mesothelin and osteopontin in 172 patients suspected of malignant pleural mesothelioma (MPM) and in a control group of 112 asymptomatic asbestos-exposed subjects.

EXPERIMENTAL DESIGN: Osteopontin and mesothelin were assayed with commercial ELISA kits in a series of 43 patients with pleural metastases of various carcinomas, 33 patients with benign pleural lesions associated with asbestos exposure, 96 patients with MPMs, and 112 asbestos-exposed healthy subjects. Results were correlated with patient's diagnosis and survival.

RESULTS: Serum osteopontin level was higher in MPM patients compared with healthy asbestos-exposed subjects and had a good capability to distinguish between these two populations. However, osteopontin was unable to distinguish between MPM and pleural metastatic carcinoma or benign pleural lesions associated with asbestos exposure. Neither plasma nor pleural fluid osteopontin were more powerful in this respect. Serum mesothelin had a good ability for diagnosing MPM but was unable to identify patients with nonepithelioid mesothelioma subtypes. Survival analysis identified tumor histologic subtype along with serum osteopontin and serum mesothelin as independent prognostic factors in mesothelioma patients.

CONCLUSIONS: Osteopontin has a lower diagnostic accuracy than mesothelin in patients suspected of MPM. Insufficient specificity limits osteopontin utility as diagnostic marker. Both molecules have a potential value as prognostic markers.}, } @article {pmid17503616, year = {2006}, author = {Gun, R and Pratt, NL and Roder, DM and Ryan, P}, title = {Asbestos-related cancers in refinery workers in the Australian petroleum industry.}, journal = {Archives of environmental & occupational health}, volume = {61}, number = {1}, pages = {11-16}, doi = {10.3200/AEOH.61.1.11-16}, pmid = {17503616}, issn = {1933-8244}, mesh = {Asbestos/*adverse effects ; Australia/epidemiology ; Cohort Studies ; Female ; Humans ; *Industry ; Interviews as Topic ; Lung Neoplasms/*epidemiology ; Mesothelioma/*epidemiology/etiology ; Occupational Diseases ; Occupational Exposure ; *Petroleum ; Registries ; }, abstract = {In this study of the incidence of asbestos-related cancer in the Australian petroleum industry, the authors traced a cohort of 16,543 petroleum industry workers for a total of 226,989 person-years. There were 18 cases of pleural mesothelioma; 12 occurred in refinery nonoffice workers, for whom the Standardized Incidence Ratio was 3.77 (95% confidence interval = 1.95-6.59). The incidence of lung cancer was significantly lower than that in the general male population. Lung cancer incidence was higher in maintenance workers than in nonmaintenance workers, but the excess was not statistically significant, as it was based on small numbers with wide confidence intervals. Lung cancer rates in refinery workers did not increase with duration of employment; however, they did tend to be higher in workers hired in earlier decades. Excess mesothelioma incidence in refinery workers is confirmed, but it is likely that there are few if any asbestos-related lung cancers.}, } @article {pmid17497698, year = {2007}, author = {Everatt, RP and Smolianskiene, G and Tossavainen, A and Cicenas, S and Jankauskas, R}, title = {Occupational asbestos exposure among respiratory cancer patients in Lithuania.}, journal = {American journal of industrial medicine}, volume = {50}, number = {6}, pages = {455-463}, doi = {10.1002/ajim.20467}, pmid = {17497698}, issn = {0271-3586}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Asbestos, Serpentine ; Asbestosis/*epidemiology/pathology ; Cross-Sectional Studies ; Female ; Humans ; Incidence ; Lung/pathology ; Lung Neoplasms/*epidemiology/pathology ; Male ; Mesothelioma/*epidemiology/pathology ; Microscopy, Electron, Scanning ; Middle Aged ; Occupational Exposure/statistics & numerical data ; Occupations/statistics & numerical data ; Pleural Neoplasms/*epidemiology/pathology ; Retrospective Studies ; Smoking/epidemiology/pathology ; }, abstract = {BACKGROUND: Despite intensive use of asbestos, no cancer case has ever been diagnosed as asbestos related in Lithuania. This paper attempts to estimate the proportion of those occupationally exposed to asbestos among respiratory cancer patients.

MATERIAL AND METHODS: Occupational exposure to asbestos was assessed retrospectively for 298 lung cancer and four mesothelioma patients, admitted to the Institute of Oncology, Vilnius. The evaluation was based on personal interview data using an internationally established questionnaire covering most likely activities of asbestos exposure at the workplace. Cumulative exposure to asbestos at work was estimated in fiber years. Lung tissue asbestos fiber burden analysis was conducted by scanning transmission electron microscopy on 23 samples.

RESULTS: A cumulative asbestos exposure of > or =25 fiber years was found for 10 lung cancer patients (3.4%). They worked in foundries, construction, installation, shipyard, power plant, railway, asbestos cement, glass and chemical industry. In a further 56 lung cancer patients (18.8%) and for one (25%) mesothelioma patient, a cumulative exposure from 5 to 24.9 fiber years was assessed. Asbestos fibers were detected in 18 cases, the burden ranged from 0.1 to 4.1 million fibers/g dry lung tissue; concentrations exceeding 1 million f/g dry lung tissue were found in four cases. All fibers were chrysotile.

CONCLUSIONS: Findings indicate that a fraction (3.4%) of the lung cancer cases could be attributed to heavy occupational exposure to asbestos using the Helsinki criterion of > or =25 fiber years. Therefore, approximately 50 lung cancer cases per year in Lithuania could be asbestos-related compensable occupational diseases.}, } @article {pmid17496929, year = {2007}, author = {Carbone, M and Albelda, SM and Broaddus, VC and Flores, RM and Hillerdal, G and Jaurand, MC and Kjaerheim, K and Pass, HI and Robinson, B and Tsao, A}, title = {Eighth international mesothelioma interest group.}, journal = {Oncogene}, volume = {26}, number = {49}, pages = {6959-6967}, doi = {10.1038/sj.onc.1210515}, pmid = {17496929}, issn = {0950-9232}, mesh = {Humans ; *Mesothelioma/etiology/pathology ; *Pleural Neoplasms/etiology/pathology ; }, abstract = {The eighth International Mesothelioma Interest Group (IMIG) meeting was held in Chicago, IL, United States, in 19-22 October 2006 to discuss mesothelioma - the cancer often linked to asbestos exposure. It is a very aggressive malignancy with a median survival of less than 1 year from diagnosis. Millions of people have been exposed worldwide to asbestos, especially during the second half of the twentieth century when asbestos use increased significantly. The tons of asbestos utilized in the past remain a health hazard for current and future generations because asbestos is difficult to be disposed off. This makes asbestos and mesothelioma research a public health issue in addition to a medical problem. Moreover, the very high costs of asbestos litigation have a significant impact on the whole economy. In the United States, up until 2001, defendant companies had paid 54 billion dollars in claims and estimated future liabilities ranged from 145 to 210 billion. Therefore, asbestos research is of great interest to a large audience that includes patients, millions of asbestos-exposed individuals, scientists, physicians, public health officials, politicians, unions of asbestos workers, lawyers and the public at large. During the past few years, there has been significant progress in understanding the process of mineral fiber carcinogenesis and mesothelioma pathogenesis. With improved understanding of the pathogenesis of mesothelioma, new diagnostic, preventive and therapeutic options are being developed. A total of 247 papers were presented at the IMIG: the abstracts of these presentations were published in Lung Cancer, Supplement 1, October 2006. Here, experts in different disciplines critically review some of the most exciting presentations of the IMIG meeting. The result is a comprehensive review of the research field of asbestos carcinogenesis and mesothelioma, and of the progress that has been made in recent years in both basic and clinical sciences.}, } @article {pmid17495698, year = {2007}, author = {Tsai, SP and Ahmed, FS and Wendt, JK and Foster, DE and Donnelly, RP and Strawmyer, TR}, title = {A 56-year mortality follow-up of Texas petroleum refinery and chemical employees, 1948-2003.}, journal = {Journal of occupational and environmental medicine}, volume = {49}, number = {5}, pages = {557-567}, doi = {10.1097/JOM.0b013e318057777c}, pmid = {17495698}, issn = {1076-2752}, mesh = {Cause of Death ; *Chemical Industry ; Cohort Studies ; Female ; Humans ; Male ; Mortality/*trends ; Occupational Health ; *Petroleum ; Texas/epidemiology ; }, abstract = {OBJECTIVE: To further investigate the mortality risk of employees who worked in the petroleum refinery industry, we updated an earlier investigation by extending the mortality follow-up by an additional 14 years through 2003.

METHODS: The cohort consisted of 10,621 employees with an average follow-up of 34 years. We used the standardized mortality ratio (SMR) adjusted for age, race, and calendar years as a measure of risk.

RESULTS: Overall mortality (SMR=0.77, 95% confidence interval [CI], 0.74-0.79), all cancer mortality (SMR=0.87, 95% CI=0.82-0.93), and most cause-specific mortalities for the total study population were lower than or similar to that of the population of Harris County, Texas. This study did not show a significant increase in leukemia in the total population or in any of the subgroups. The only statistically significant excess of mortality found in this study was an increase in mesothelioma among maintenance employees; the SMR was 4.78 (95% CI=2.54-8.17) among employees who worked for a minimum of one year and was 7.51 (95% CI=3.75-13.45) among those with 10 or more years of employment and 20 or more years of latency.

CONCLUSIONS: After more than half a century of follow-up, employees at this facility continue to show more favorable mortality outcomes than the general local population. Overall, no statistically significant increase of leukemia or of any of the specific cell types was found. The increased mesothelioma is likely related to past exposure to asbestos.}, } @article {pmid17493236, year = {2007}, author = {Frey, AB and Wali, A and Pass, H and Lonardo, F}, title = {Osteopontin is linked to p65 and MMP-9 expression in pulmonary adenocarcinoma but not in malignant pleural mesothelioma.}, journal = {Histopathology}, volume = {50}, number = {6}, pages = {720-726}, doi = {10.1111/j.1365-2559.2007.02675.x}, pmid = {17493236}, issn = {0309-0167}, mesh = {Adenocarcinoma/diagnosis/genetics/*metabolism ; Biomarkers, Tumor/genetics/metabolism ; Cell Proliferation ; Diagnosis, Differential ; ErbB Receptors/physiology ; Extracellular Signal-Regulated MAP Kinases/physiology ; Gene Expression Regulation, Neoplastic ; Humans ; Lung/metabolism/pathology ; Lung Neoplasms/diagnosis/genetics/*metabolism ; Matrix Metalloproteinase 9/genetics/*metabolism ; Mesothelioma/diagnosis/genetics/*metabolism ; Osteopontin/genetics/*metabolism ; Pleural Neoplasms/diagnosis/genetics/*metabolism ; Signal Transduction/physiology ; Transcription Factor RelA/genetics/*metabolism ; }, abstract = {AIMS: Osteopontin (OPN) is a matricellular protein involved in tissue remodelling, cell-mediated immunity and malignant transformation. High OPN serum levels predict poor prognosis in non-small cell carcinoma and set patients with malignant pleural mesothelioma (MM) apart from disease-free asbestos-exposed individuals. Yet neither the spectrum of tissue expression nor the signalling pathways of OPN in MM and pulmonary adenocarcinoma have been characterized, although in vitro evidence links OPN to the epidermal growth factor receptor (EGFR) pathway. The aim of this study was to address these deficiencies.

METHODS AND RESULTS: OPN expression was investigated immunohistochemically in 104 adenocarcinomas and 38 MM and correlated with histological features, including tumour type, grade and proliferation and with expression of activated intermediary EGFR signalling pathway molecules p65, p-AKT, p-ERK, p-STAT-3, and of metalloproteinase (MMP)-1, MMP-2 and MMP-9. In MM, OPN expression was widespread (36/38) and independent of the molecular parameters studied. In adenocarcinoma, high OPN expression was correlated with expression of p65, p-ERK and MMP-9.

CONCLUSIONS: Frequent OPN expression is typical of, but not specific for MM, whereas it appears to select adenocarcinoma cases with p65 and MMP-9 expression, suggesting a link with EGFR signalling pathways.}, } @article {pmid17492119, year = {2007}, author = {Chaisaowong, K and Aach, T and Jäger, P and Vogel, S and Knepper, A and Kraus, T}, title = {Computer-assisted diagnosis for early stage pleural mesothelioma: towards automated detection and quantitative assessment of pleural thickening from thoracic CT images.}, journal = {Methods of information in medicine}, volume = {46}, number = {3}, pages = {324-331}, doi = {10.1160/ME9050}, pmid = {17492119}, issn = {0026-1270}, mesh = {Diagnosis, Computer-Assisted/*methods ; Early Diagnosis ; Germany ; Humans ; Image Processing, Computer-Assisted/*methods ; Pleural Neoplasms/*diagnosis/*diagnostic imaging ; Radiography, Thoracic ; *Tomography, X-Ray Computed ; }, abstract = {OBJECTIVES: Pleural thickenings as biomarker of exposure to asbestos may evolve into malignant pleural mesothelioma. For its early stage, pleurectomy with perioperative treatment can reduce morbidity and mortality. The diagnosis is based on a visual investigation of CT images, which is a time-consuming and subjective procedure. Our aim is to develop an automatic image processing approach to detect and quantitatively assess pleural thickenings.

METHODS: We first segment the lung areas, and identify the pleural contours. A convexity model is then used together with a Hounsfield unit threshold to detect pleural thickenings. The assessment of the detected pleural thickenings is based on a spline-based model of the healthy pleura.

RESULTS: Tests were carried out on 14 data sets from three patients. In all cases, pleural contours were reliably identified, and pleural thickenings detected. PC-based Computation times were 85 min for a data set of 716 slices, 35 min for 401 slices, and 4 min for 75 slices, resulting in an average computation time of about 5.2 s per slice. Visualizations of pleurae and detected thickenings were provided.

CONCLUSION: Results obtained so far indicate that our approach is able to assist physicians in the tedious task of finding and quantifying pleural thickenings in CT data. In the next step, our system will undergo an evaluation in a clinical test setting using routine CT data to quantify its performance.}, } @article {pmid17484626, year = {2007}, author = {Di Serio, F and Fontana, A and Loizzi, M and Capotorto, G and Maggiolini, P and Mera, E and Bisceglia, L and Molinini, R}, title = {Mesothelin family proteins and diagnosis of mesothelioma: analytical evaluation of an automated immunoassay and preliminary clinical results.}, journal = {Clinical chemistry and laboratory medicine}, volume = {45}, number = {5}, pages = {634-638}, doi = {10.1515/CCLM.2007.112}, pmid = {17484626}, issn = {1434-6621}, mesh = {Aged ; Automation ; Biomarkers, Tumor ; Case-Control Studies ; Enzyme-Linked Immunosorbent Assay/instrumentation/*methods/standards ; Female ; GPI-Linked Proteins ; Humans ; Male ; Membrane Glycoproteins/*blood ; Mesothelin ; Mesothelioma/*diagnosis ; Middle Aged ; Reproducibility of Results ; Sensitivity and Specificity ; }, abstract = {BACKGROUND: Studies have suggested that soluble mesothelin-related protein (SMRP) can be used as a serum marker of malignant mesothelioma.

METHODS: We assessed the analytical performance of the Mesomark (Fujirebio Diagnostic) two-step ELISA on an automated analyser and performed a preliminary clinical evaluation. The precision of the assay and the in vitro effect of interfering substances on SMRP concentrations were investigated. The serum marker was analysed in 109 healthy subjects never exposed to asbestos, 26 healthy subjects exposed to asbestos, 33 patients with asbestosis, 33 with asbestos-related pleural plaques, 10 with non-malignant pleural diseases, 30 with lung cancer and 24 with histological diagnosis of pleural mesothelioma.

RESULTS: Using the International Mesothelioma Interest Group classification, there were nine stage IV, two stage III, four stage II and nine stage I patients. SMRP concentrations of 4.75, 11.0 and 14 nmol/mL showed a total imprecision of 3.5%, 3.1% and 3.8%. The detection limit was 0.035 nmol/mL; the mean SMRP concentration of 0.63 nmol/mL was associated with a coefficient of variation of 10%. There was no effect (p>0.05) of interfering substances. Serum samples from patients with established pleural mesothelioma had significantly higher (p<0.05) concentrations of SMRP than control healthy and patient groups.

CONCLUSIONS: SMRP measured on automated systems could be useful for the diagnosis of mesothelioma in routine clinical practice.}, } @article {pmid17475364, year = {2007}, author = {Witherby, SM and Butnor, KJ and Grunberg, SM}, title = {Malignant mesothelioma following thoracic radiotherapy for lung cancer.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {57}, number = {3}, pages = {410-413}, doi = {10.1016/j.lungcan.2007.03.016}, pmid = {17475364}, issn = {0169-5002}, mesh = {Adolescent ; Adult ; Female ; Humans ; Lung Neoplasms/*radiotherapy ; Male ; Mesothelioma/*diagnosis/etiology ; Middle Aged ; Neoplasms, Radiation-Induced/*diagnosis ; Neoplasms, Second Primary/*diagnosis/etiology ; Pleural Neoplasms/*diagnosis/etiology ; }, abstract = {As the number of long-term cancer survivors increases, secondary malignancies are becoming a greater clinical issue. Although some of these malignancies may be related to common environmental exposures, a significant number are considered to be therapy-related. Pleural malignant mesothelioma is a neoplasm that may be related to asbestos exposure or radiation exposure. Previous reports of pleural mesothelioma as a second malignancy have tended to follow radiotherapy for extra-thoracic malignancies such as Hodgkin's disease, breast cancer and Wilms' tumor. We report the case of a 66-year-old woman with no prior asbestos exposure who developed pleural mesothelioma 17 years after pneumonectomy and adjuvant radiation therapy for non-small cell lung cancer. Opacification of the lung field from prior therapy made determination of the diagnosis more challenging. Secondary malignancies such as mesothelioma should be considered in patients who develop unexplained symptoms even long after treatment of a primary tumor.}, } @article {pmid17466159, year = {2007}, author = {Al-Qahtani, M and Morris, B and Dawood, S and Onerheim, R}, title = {Malignant mesothelioma of the tunica vaginalis.}, journal = {The Canadian journal of urology}, volume = {14}, number = {2}, pages = {3514-3517}, pmid = {17466159}, issn = {1195-9479}, mesh = {Adult ; Diagnosis, Differential ; Humans ; Male ; Mesothelioma/*diagnosis/pathology ; Testicular Neoplasms/*diagnosis/pathology ; }, abstract = {INTRODUCTION: Malignant mesothelioma involving the tunica vaginalis is an extremely rare tumor.

CASE: We describe a case of a 39-year-old man who initially presented with discomfort in the left testis and underwent resection of a hydrocele in the left testis. A pathology examination of a frozen section of a lesion on the tunica identified the lesion as mesothelioma, which was confirmed by a second pathology examination. No metastatic disease was found. The patient subsequently underwent a left radical orchiectomy and a partial scrotectomy, and has been disease free for 7 years.

DISCUSSION: The first case of malignant mesothelioma involving the tunica vaginalis, a structure embryologically derived from a layer of reflected peritoneum known as the "processus vaginalis," was reported in 1957. Only 73 cases were reported in the literature between 1966 and 1997. In up to 41% of cases, there is a positive history of asbestos exposure. Young age and localized disease are associated with a better prognosis. Radical orchiectomy limits recurrence, which usually occurs within 2 years, but may occur up to 15 years after surgery.}, } @article {pmid17455866, year = {2007}, author = {Bianchi, C and Bianchi, T and Ramani, L}, title = {Malignant mesothelioma of the pleura and other malignancies in the same patient.}, journal = {Tumori}, volume = {93}, number = {1}, pages = {19-22}, doi = {10.1177/030089160709300104}, pmid = {17455866}, issn = {0300-8916}, mesh = {Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Female ; Humans ; Male ; Mesothelioma/epidemiology/*pathology ; Middle Aged ; Neoplasms, Multiple Primary/*epidemiology ; Occupational Exposure/adverse effects ; Pleural Neoplasms/epidemiology/*pathology ; }, abstract = {AIMS AND BACKGROUND: The co-existence of mesothelioma, mostly asbestos-related, and other primary malignancies has repeatedly been reported. The present study evaluated the frequency of such an occurrence.

METHODS: In the period October 1979-June 2002, 215 cases of malignant pleural mesothelioma were diagnosed at the Hospital of Monfalcone, Italy. All the cases of the above series, examined at necropsy (169), were included in the study. Occupational histories had been obtained from the patients or from their relatives by personal or telephone interviews. In 132 cases, asbestos bodies were isolated after chemical digestion of lung samples. The thoracic cavities were examined for pleural plaques.

RESULTS: Additional malignancies were observed in 32 cases (18.9%). Multiple tumors were synchronous in 22 cases, metachronous in 8 cases, and synchronous and metachronous in 2. Four different tumors were found in 2 cases, 3 malignancies were detected in 6 patients, and 2 malignancies in the remaining 24. The most frequent additional malignancies were prostate adenocarcinoma (7 cases), non-Hodgkin lymphoma or chronic lymphocytic leukaemia (5 cases), bladder carcinoma (4 cases), kidney carcinoma (4 cases), large bowel carcinoma (4 cases), and liver cell carcinoma (4 cases). All the patients had histories of exposure to asbestos, mostly in shipbuilding. Lung asbestos body burdens ranged between 60 and 230,000 per gram of dried tissue. Pleural plaques were found in 26 cases.

CONCLUSIONS: In contrast with other series of the literature, in the present cases the co-existence of mesothelioma and other malignancies appeared as a relatively frequent event. The lack of a control group does not allow definite conclusions about the meaning of the occurrence. However, the co-existence of certain tumors with asbestos-related mesothelioma suggests that mesothelioma and associated malignancies might share some etiologic factors (asbestos and others).}, } @article {pmid17450227, year = {2007}, author = {Sullivan, PA}, title = {Vermiculite, respiratory disease, and asbestos exposure in Libby, Montana: update of a cohort mortality study.}, journal = {Environmental health perspectives}, volume = {115}, number = {4}, pages = {579-585}, pmid = {17450227}, issn = {0091-6765}, mesh = {Aged ; Aluminum Silicates/*adverse effects ; Asbestos, Amphibole/*adverse effects ; Asbestosis/*mortality ; Cohort Studies ; Humans ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/mortality ; Middle Aged ; Mining ; Montana/epidemiology ; *Occupational Exposure ; Pleural Neoplasms/mortality ; Retrospective Studies ; }, abstract = {BACKGROUND: Vermiculite from the mine near Libby, Montana, is contaminated with tremolite asbestos and other amphibole fibers (winchite and richterite). Asbestos-contaminated Libby vermiculite was used in loose-fill attic insulation that remains in millions of homes in the United States, Canada, and other countries.

OBJECTIVE: This report describes asbestos-related occupational respiratory disease mortality among workers who mined, milled, and processed the Libby vermiculite.

METHODS: This historical cohort mortality study uses life table analysis methods to compare the age-adjusted mortality experience through 2001 of 1,672 Libby workers to that of white men in the U.S. population.

RESULTS: Libby workers were significantly more likely to die from asbestosis [standardized mortality ratio (SMR) = 165.8; 95% confidence interval (CI), 103.9-251.1], lung cancer (SMR = 1.7; 95% CI, 1.4-2.1), cancer of the pleura (SMR = 23.3; 95% CI, 6.3-59.5), and mesothelioma. Mortality from asbestosis and lung cancer increased with increasing duration and cumulative exposure to airborne tremolite asbestos and other amphibole fibers.

CONCLUSIONS: The observed dose-related increases in asbestosis and lung cancer mortality highlight the need for better understanding and control of exposures that may occur when homeowners or construction workers (including plumbers, cable installers, electricians, telephone repair personnel, and insulators) disturb loose-fill attic insulation made with asbestos-contaminated vermiculite from Libby, Montana.}, } @article {pmid17449563, year = {2007}, author = {Hein, MJ and Stayner, LT and Lehman, E and Dement, JM}, title = {Follow-up study of chrysotile textile workers: cohort mortality and exposure-response.}, journal = {Occupational and environmental medicine}, volume = {64}, number = {9}, pages = {616-625}, pmid = {17449563}, issn = {1470-7926}, mesh = {Adult ; Aged ; Asbestos, Serpentine/*toxicity ; Epidemiologic Methods ; Female ; Humans ; Lung Neoplasms/etiology/*mortality ; Male ; Middle Aged ; Occupational Diseases/etiology/*mortality ; Occupational Exposure/*adverse effects ; Textile Industry/*statistics & numerical data ; }, abstract = {OBJECTIVES: This report provides an update of the mortality experience of a cohort of South Carolina asbestos textile workers.

METHODS: A cohort of 3072 workers exposed to chrysotile in a South Carolina asbestos textile plant (1916-77) was followed up for mortality through 2001. Standardised mortality ratios (SMRs) were computed using US and South Carolina mortality rates. A job exposure matrix provided calendar time dependent estimates of chrysotile exposure concentrations. Poisson regression models were fitted for lung cancer and asbestosis. Covariates considered included sex, race, age, calendar time, birth cohort and time since first exposure. Cumulative exposure lags of 5 and 10 years were considered by disregarding exposure in the most recent 5 and 10 years, respectively.

RESULTS: A majority of the cohort was deceased (64%) and 702 of the 1961 deaths occurred since the previous update. Mortality was elevated based on US referent rates for a priori causes of interest including all causes combined (SMR 1.33, 95% CI 1.28 to 1.39); all cancers (SMR 1.27, 95% CI 1.16 to 1.39); oesophageal cancer (SMR 1.87, 95% CI 1.09 to 2.99); lung cancer (SMR 1.95, 95% CI 1.68 to 2.24); ischaemic heart disease (SMR 1.20, 95% CI 1.10 to 1.32); and pneumoconiosis and other respiratory diseases (SMR 4.81, 95% CI 3.84 to 5.94). Mortality remained elevated for these causes when South Carolina referent rates were used. Three cases of mesothelioma were observed among cohort members. Exposure-response modelling for lung cancer, using a linear relative risk model, produced a slope coefficient of 0.0198 (fibre-years/ml) (standard error 0.00496), when cumulative exposure was lagged 10 years. Poisson regression modelling confirmed significant positive relations between estimated chrysotile exposure and lung cancer and asbestosis mortality observed in previous updates of this cohort.

CONCLUSIONS: This study confirms the findings from previous investigations of excess mortality from lung cancer and asbestosis and a strong exposure-response relation between estimated exposure to chrysotile and mortality from lung cancer and asbestosis.}, } @article {pmid17449562, year = {2007}, author = {Clements, M and Berry, G and Shi, J and Ware, S and Yates, D and Johnson, A}, title = {Projected mesothelioma incidence in men in New South Wales.}, journal = {Occupational and environmental medicine}, volume = {64}, number = {11}, pages = {747-752}, pmid = {17449562}, issn = {1470-7926}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Asbestos, Amphibole/toxicity ; Confidence Intervals ; Forecasting ; Humans ; Incidence ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Models, Statistical ; New South Wales/epidemiology ; Occupational Diseases/*epidemiology/etiology ; Occupational Exposure/adverse effects ; }, abstract = {OBJECTIVES: Based on observed numbers of incident mesotheliomas since 1972, to predict future numbers in men in New South Wales.

METHODS: The incidence of mesothelioma was modelled in two ways. First by using an age/birth cohort model, and second by using a model based on potential exposure to asbestos in terms of age and calendar year. The latter model included a term for clearance of asbestos fibres from the lungs, and a term for diagnostic fraction. The age and calendar year model was based on the model introduced by Hodgson and colleagues but replaced piecewise effects by smooth functions represented by cubic splines.

RESULTS: The number of mesotheliomas between 2004 and 2060 was predicted as 6690 with the age-cohort model and as 6779 by the age and calendar year model, with peak annual numbers of 187 in the year 2021 and 196 in the year 2014 with the two models respectively.

CONCLUSIONS: The pattern of parameter estimates in the two models was in accord with the known use of amphibole asbestos in Australia. The predicted peak year of 2014-21 is 30-35 years after the phasing out of amphibole use, and this period is in accord with predictions for the UK and the US; in the latter country the peak was 10-15 years earlier corresponding to a marked decline of amphibole use in and following the 1960s.}, } @article {pmid17442515, year = {2007}, author = {Le Neindre, B and Bouvier, V and Galateau-Sallé, F and de Quillacq, A and Launoy, G and Letourneux, M}, title = {[Compensation of malignant mesothelioma as an occupational disease in Lower Normandy, from 1995 to 2002].}, journal = {Revue d'epidemiologie et de sante publique}, volume = {55}, number = {2}, pages = {123-131}, doi = {10.1016/j.respe.2006.10.002}, pmid = {17442515}, issn = {0398-7620}, mesh = {Aged ; *Compensation and Redress ; Female ; France/epidemiology ; Humans ; Lung Neoplasms/*economics/epidemiology ; Male ; Mesothelioma/*economics/epidemiology ; Occupational Diseases/*economics ; }, abstract = {BACKGROUND: Despite the close relation between occupational exposure to asbestos and malignant mesothelioma, the compensation of this disease is still far from being the rule. The objective of this study is to assess the compensation process of all the cases of occupational mesothelioma recorded by the regional mesothelioma registry between September 1995 and August 2002, and to make suggestions for improvement of the compensation of future cases.

METHODS: Lifetime exposure to asbestos was assessed for each of the 141 mesothelioma cases observed in Lower Normandy during this time period, and 105 cases could be related to a possible, probable, or very probable occupational exposure to this mineral. Data about notification and compensation of these occupational diseases were gathered with the help of all health insurance organisms concerned.

RESULTS: Except for five cases in which insurance conditions did not allow any compensation, compensation of occupational mesothelioma occurred in 85% of the cases. This high rate was probably the result of the existence of an early asbestos industry in this region, and of the particular awareness of the Norman population about asbestos-related diseases, as well as of the epidemiological follow-up of mesothelioma in Lower Normandy. When notified for compensation, all cases but one were actually compensated, and the lag-time between notification and compensation proved to decrease since 1995, with an average delay reaching 91,1 days in 2002. Patients who did not report their disease were older than those who did, and the lack of knowledge of medical practitioners about compensation procedures seems to be an important matter in this issue.

CONCLUSION: In order to improve the rate of compensation of occupational malignant mesothelioma cases, information about the usual occupational origin of the disease should be delivered systematically to the general practitioner of each patient. This could be done by pathologists, when they diagnose malignant mesothelioma, and/or by medical examiners when sickness benefits are sought, or even by the epidemiological center of death causes (INSERM, CépiDc), for the beneficiaries of patients who died from malignant mesothelioma.}, } @article {pmid17440075, year = {2007}, author = {Pietruska, JR and Kane, AB}, title = {SV40 oncoproteins enhance asbestos-induced DNA double-strand breaks and abrogate senescence in murine mesothelial cells.}, journal = {Cancer research}, volume = {67}, number = {8}, pages = {3637-3645}, doi = {10.1158/0008-5472.CAN-05-3727}, pmid = {17440075}, issn = {0008-5472}, support = {P42 ES 013660/ES/NIEHS NIH HHS/United States ; R01 ES 03721/ES/NIEHS NIH HHS/United States ; T32 ES 07272/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Antibiotics, Antineoplastic/*pharmacology ; Antigens, Polyomavirus Transforming/biosynthesis/genetics/*physiology ; Asbestos/*pharmacology ; Bleomycin/*pharmacology ; Cell Growth Processes/physiology ; Cell Line ; Cellular Senescence ; DNA/drug effects/metabolism ; *DNA Damage ; Epithelial Cells/cytology/drug effects/physiology ; Humans ; Mice ; Transfection ; Tumor Suppressor Protein p53/deficiency/metabolism ; beta-Galactosidase/metabolism ; }, abstract = {SV40 virus has emerged as a potential cofactor with asbestos in the development of diffuse malignant mesothelioma, but its precise role in the pathogenesis of this tumor is unclear. SV40 large T antigen is known to inactivate cellular proteins involved in DNA damage and senescence, including p53 and pRb. We hypothesize that SV40 oncoproteins will sensitize mesothelial cells to DNA damage induced by asbestos or chemotherapeutic agents. SV40 oncoprotein expression in murine mesothelial cell lines enhanced spontaneous and asbestos-induced double-strand breaks, indicated by gamma-H2AX foci, and potentiated micronucleus formation. Mesothelial cells exposed to asbestos or bleomycin for 96 h acquired senescent-like morphology and displayed elevated senescence-associated beta-galactosidase activity, reduced bromodeoxyuridine (BrdUrd) incorporation, and reduced colony formation. SV40 oncoprotein expression abrogated the senescent phenotype, and transfected cell lines showed an increase in both BrdUrd incorporation and colony formation after prolonged DNA damage. Murine mesothelial cell lines lacking wild-type p53 due to a point mutation or gene rearrangement also failed to senesce in response to asbestos or chemotherapeutic agents. In addition, stress-induced senescence in human mesothelial cell lines was impaired by SV40 oncoprotein expression (MeT-5A), p53 small interfering RNA, or spontaneous p53 mutation (REN). These studies suggest that exposure to DNA-damaging agents can induce senescence in both murine and human mesothelioma cell lines and suggest a major, although not exclusive, role for p53 in this response. SV40 virus may contribute to mesothelioma progression by impairing stress-induced senescence, in part through p53 inactivation, thereby favoring survival and proliferation of mesothelial cells that have sustained DNA damage.}, } @article {pmid17434931, year = {2007}, author = {Aung, W and Hasegawa, S and Furukawa, T and Saga, T}, title = {Potential role of ferritin heavy chain in oxidative stress and apoptosis in human mesothelial and mesothelioma cells: implications for asbestos-induced oncogenesis.}, journal = {Carcinogenesis}, volume = {28}, number = {9}, pages = {2047-2052}, doi = {10.1093/carcin/bgm090}, pmid = {17434931}, issn = {0143-3334}, mesh = {Apoferritins/*physiology ; Apoptosis/drug effects/*physiology ; Asbestos/*toxicity ; Cell Line ; Epithelium/pathology ; Humans ; Hydrogen Peroxide/metabolism ; Mesothelioma/chemically induced/pathology/*physiopathology ; Oxidative Stress/*physiology ; Pleura/*cytology/drug effects/pathology ; }, abstract = {Exposure to asbestos is a known etiological factor in malignant mesothelioma (MM). However, in vitro cell culture studies have provided paradoxical evidence that asbestos exposure to mesothelial cells causes cytotoxicity or apoptosis rather than malignant transformation. Although it has been shown that the iron associated with asbestos participates in the cell toxicity and probably MM pathogenesis via generation of reactive oxygen species (ROS), the molecular mechanisms largely remain unknown. Here, we demonstrate that ferritin heavy chain (FHC), a core subunit of iron-binding protein ferritin, works as an anti-apoptotic protein against toxic asbestos and oxidative stress in human mesothelial cells and MM cells. We found that FHC was induced in asbestos-exposed MeT-5A human mesothelial cells. The mesothelial cell line stably expressing FHC generated less amount of hydrogen peroxide (H2O2), one of the main ROS, after asbestos exposure and was more resistant to apoptosis induced by H2O2 compared with the cells transfected with the empty vector. Next, we investigated biological roles of FHC in human MM cell. We found that NCI-H2052, a human MM cell line, had a higher expression of endogenous FHC than MeT-5A and used the cell to address FHC function in MM. NCI-H2052 showed reduced H2O2 production and an apoptosis-resistant phenotype compared with MeT-5A. Suppression of the over-expressed FHC by using FHC small interfering RNA rendered the MM cells sensitive to apoptosis, suggesting the contribution of FHC to apoptosis resistance of the MM cells. Our findings highlight the potential role of FHC in the pathogenesis of asbestos-induced mesothelioma.}, } @article {pmid17427359, year = {2007}, author = {Tarry, SL}, title = {More about differential peeky bias.}, journal = {International journal of occupational and environmental health}, volume = {13}, number = {1}, pages = {133-4; author reply 134-6}, pmid = {17427359}, issn = {1077-3525}, mesh = {Asbestos/*adverse effects ; Automobiles ; Causality ; Conflict of Interest ; Evaluation Studies as Topic ; Humans ; Industry ; Mesothelioma/etiology ; Occupational Diseases/epidemiology/*etiology ; Occupational Exposure/*adverse effects/statistics & numerical data ; Science/methods ; United States/epidemiology ; }, } @article {pmid17427351, year = {2007}, author = {Tweedale, G}, title = {The Rochdale asbestos cancer studies and the politics of epidemiology: what you see depends on where you sit.}, journal = {International journal of occupational and environmental health}, volume = {13}, number = {1}, pages = {70-79}, doi = {10.1179/107735207800245045}, pmid = {17427351}, issn = {1077-3525}, mesh = {Asbestos/*history/toxicity ; Asbestosis/epidemiology/history ; History, 20th Century ; History, 21st Century ; Humans ; Lung Neoplasms/epidemiology/*history ; Mesothelioma/epidemiology/*history ; Occupational Diseases/epidemiology/*history ; *Politics ; United Kingdom/epidemiology ; }, abstract = {The history of the exploitation of epidemiology by the U.K. asbestos industry and the subsequent obscuring of the disastrous results of exposures is presented, exploring in particular the roles of Sir Richard Doll and his colleagues. Epidemiology, often regarded as a neutral science, is susceptible to socio-political influences.}, } @article {pmid17427350, year = {2007}, author = {Tomatis, L and Cantoni, S and Carnevale, F and Merler, E and Mollo, F and Ricci, P and Silvestri, S and Vineis, P and Terracini, B}, title = {The role of asbestos fiber dimensions in the prevention of mesothelioma.}, journal = {International journal of occupational and environmental health}, volume = {13}, number = {1}, pages = {64-69}, doi = {10.1179/107735207800245036}, pmid = {17427350}, issn = {1077-3525}, mesh = {Asbestos/*toxicity ; Humans ; Mesothelioma/*etiology/*prevention & control ; *Mineral Fibers ; Occupational Exposure/*adverse effects ; Particle Size ; Pleural Neoplasms/*etiology/*prevention & control ; }, abstract = {A recent interpretation of the pathogenetic role of asbestos fiber size in the development of mesothelioma and in the possibility of mesothelioma prevention needs clarification. This point of view is based on a biased interpretation of the literature. Epidemiologic, experimental, and molecular evidence suggests that the arguments for the role of fiber size relative to dose, dose-response effect, and genetic susceptibility are scientifically unsound. Their proponent also states that means available in the past for the implementation of dust-control measures and/or personal protective equipment would not have contributed to reducing the frequency of mesothelioma among exposed subjects, an argument again based on invalid assumptions.}, } @article {pmid17426518, year = {2007}, author = {Bianchi, C and Bianchi, T}, title = {Malignant mesothelioma in telephone workers.}, journal = {Journal of occupational and environmental medicine}, volume = {49}, number = {4}, pages = {359}, doi = {10.1097/JOM.0b013e318046eb20}, pmid = {17426518}, issn = {1076-2752}, mesh = {Asbestos/toxicity ; Electric Wiring ; Humans ; Italy/epidemiology ; Mesothelioma/*diagnosis/epidemiology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*diagnosis/epidemiology ; Telephone ; }, } @article {pmid17419436, year = {2007}, author = {Inoue, C and Kato, S and Higuchi, K and Inoue, H}, title = {[A case of malignant pleural mesothelioma with elevation of G-CSF and CYFRA in the serum and pleural fluid].}, journal = {Nihon Kokyuki Gakkai zasshi = the journal of the Japanese Respiratory Society}, volume = {45}, number = {3}, pages = {243-247}, pmid = {17419436}, issn = {1343-3490}, mesh = {Aged ; Antigens, Neoplasm/*metabolism ; Biomarkers, Tumor/metabolism ; Granulocyte Colony-Stimulating Factor/*biosynthesis ; Humans ; Hyaluronan Receptors ; Keratin-19 ; Keratins/*metabolism ; Male ; Mesothelioma/diagnosis/*metabolism ; Pleural Effusion/*metabolism ; Pleural Neoplasms/diagnosis/*metabolism ; Staining and Labeling ; }, abstract = {A 68-year-old man complaining of hoarseness and back pain, with no history of exposure to asbestos, was referred to our hospital in June 2002. He was admitted because his chest X-ray and CT scan showed atelectasis and a tumor-like region in the right lower lobe of the lung. Serum-CYFRA was 2.8 ng/ml, elevated slightly; however, no other tumor markers for lung cancer were elevated. A diagnosis of squamous cell lung cancer was made based on bronchial washing cytology. Persistent high fever and WBC count elevation did not respond to antibiotics, and reduced only after chemotherapy. Both serum G-CSF (217.0 pg/ml) and CYFRA in the pleural effusion (107.1 ng/ml) were elevated. The biopsy of the growing tumor in the right lateral abdominal wall revealed carcinoma with sarcomatous component or biphasic-type malignant pleural mesothelioma (MPM). In spite of chemotherapy and radiation therapy for the abdominal wall tumor, the tumor rapidly progressed and the patient died three months after admission. The findings at autopsy suggested the tumor was a sarcomatous MPM. However, immunohistochemical staining and tissue HABP staining revealed biphasic type MPM. Although CYFRA elevation in the serum and/or the pleural effusion in MPM patients has been previously reported, it has not been reported in any of the 5 MPM patients reported to have G-CSF elevation. Therefore, this is the first reported case of G-CSF-producing MPM with CYFRA elevation in both serum and the pleural effusion.}, } @article {pmid17415923, year = {2007}, author = {Kapur, U and Wojcik, EM}, title = {Fine-needle aspiration of malignant mesothelioma with unusual morphologic features: a case report.}, journal = {Diagnostic cytopathology}, volume = {35}, number = {3}, pages = {174-178}, doi = {10.1002/dc.20605}, pmid = {17415923}, issn = {8755-1039}, mesh = {Aged, 80 and over ; Biopsy, Fine-Needle ; Humans ; Lung/pathology ; Male ; Mesothelioma/*diagnosis/*pathology ; Microvilli/ultrastructure ; Pleural Effusion, Malignant/pathology ; Pleural Neoplasms/*diagnosis/*pathology ; }, abstract = {Malignant mesothelioma is an aggressive neoplasm linked to asbestos exposure. Most mesothelioma patients present with pleural effusion and the fluid is typically sent for cytological examination. Therefore, cytopathologists are most familiar with features of mesothelioma in fluid preparations. We present here a case of malignant mesothelioma with unusual cytological features diagnosed on FNA. The diagnosis was confirmed by immuno-histochemical and electron microscopic studies. In addition, we compare the cytomorphological features observed in malignant effusion versus fine-needle aspiration.}, } @article {pmid17407142, year = {2007}, author = {Ascoli, V and Cavone, D and Merler, E and Barbieri, PG and Romeo, L and Nardi, F and Musti, M}, title = {Mesothelioma in blood related subjects: report of 11 clusters among 1954 Italy cases and review of the literature.}, journal = {American journal of industrial medicine}, volume = {50}, number = {5}, pages = {357-369}, doi = {10.1002/ajim.20451}, pmid = {17407142}, issn = {0271-3586}, mesh = {Adult ; Aged ; Asbestos/*toxicity ; Cluster Analysis ; Disease Susceptibility ; Environmental Exposure/*adverse effects ; Female ; Humans ; Italy/epidemiology ; Male ; Medical History Taking ; Mesothelioma/epidemiology/*genetics ; Middle Aged ; Occupational Exposure/*adverse effects ; Risk Assessment ; Risk Factors ; }, abstract = {BACKGROUND: Malignant mesothelioma is a sporadic tumor related to asbestos. Its occurrence in blood relatives raises the question of potential contribution of predisposing factors.

METHODS: The study analyses the features of mesothelioma in blood relatives that might explain the disease clustering. Data sources of familial clusters were three population-based Mesothelioma Registries in Italy (Veneto and Apulia Regions, Brescia province; 1978-2005) and Medline, Toxline, and Oshline/Hseline databases for a review of the literature (1968-2006).

RESULTS: Eleven clusters (22 cases) were identified among 1954 Italy mesothelioma cases, and 51 clusters (120 cases) were extracted from 33 studies. The proportion of Italy familial cases was 1.4 per 100 mesothelioma cases; the ratio between the number of familial clusters and the number of non-familial mesothelioma cases was 1:148. The mesothelioma profile in consanguineous is the same as in non-consanguineous subjects (male prevalence; pleural site; age at diagnosis >50 years; asbestos exposure). Most clusters occurred in asbestos workers (shipyard, asbestos-cement production/processing, and insulation) and household-exposed blood relatives. Others were related to asbestos-cement factory pollution, asbestos-in-place, and handling asbestos-contaminated textiles. Two clusters were without any known exposure. Cancer family history revealed lung cancer cases in eight clusters.

CONCLUSIONS: Available data support asbestos exposure as the main risk factor in mesothelioma cases among blood relatives. Our finding of a low proportion of familial cases would not suggest the influence of a large genetic component for mesothelioma in blood relatives.}, } @article {pmid17400330, year = {2007}, author = {Wilkins, A and Popat, S and Hughes, S and O'Brien, M}, title = {Malignant pleural mesothelioma: two cases in first degree relatives.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {57}, number = {3}, pages = {407-409}, doi = {10.1016/j.lungcan.2007.02.005}, pmid = {17400330}, issn = {0169-5002}, mesh = {Adult ; Antineoplastic Agents/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Asbestos/toxicity ; Family ; Humans ; Male ; Mesothelioma/*diagnostic imaging/drug therapy/genetics ; Middle Aged ; Platinum/therapeutic use ; Pleural Neoplasms/*diagnostic imaging/drug therapy/genetics ; Tomography, X-Ray Computed ; }, abstract = {We report two cases of malignant pleural mesothelioma in first degree relatives arising within weeks of each other. The patients had a shared exposure to asbestos and age difference of over 20 years at time of presentation. In both cases, the anatomical pattern was similar and unusual for mesothelioma and initial histology was reported for both as non-small cell lung cancer. Both patients were treated with platinum-based combination chemotherapy.}, } @article {pmid17394680, year = {2007}, author = {Becklake, MR and Bagatin, E and Neder, JA}, title = {Asbestos-related diseases of the lungs and pleura: uses, trends and management over the last century.}, journal = {The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease}, volume = {11}, number = {4}, pages = {356-369}, pmid = {17394680}, issn = {1027-3719}, mesh = {*Asbestosis/complications/diagnosis/epidemiology/therapy ; Humans ; Lung Neoplasms/epidemiology/etiology ; Mesothelioma/epidemiology/etiology ; Mineral Fibers ; Pleural Diseases/therapy ; Workplace ; }, abstract = {Asbestos is a descriptive term for a group of naturally occurring minerals known to mankind since ancient times. The main types of asbestos (chrysotile, and the amphiboles crocidolite and amosite) differ in chemical structure, biopersistence in human tissue and toxicity. Commercial exploitation, with little thought for environmental controls, increased over the twentieth century, particularly after World War II, to accommodate globalisation and the demands of the world's burgeoning cities. As its ill-health effects, both non-malignant (fibrosis of the lungs or asbestosis; pleural effusion, plaques and thickening) and malignant (mesothelioma, lung and other cancers), became evident, public pressure rose to control its use. The last decades of the last century saw decreases in exposure and rates of asbestosis in industrialised and in some less-industrialised countries, where pleural plaques and malignant mesothelioma are currently the most frequent manifestations of asbestos exposure. Longer follow-up of asbestos-exposed cohorts in mining and manufacturing has also strengthened the evidence of a fibre gradient in toxicity, with chrysotile exhibiting lower toxicity than the amphiboles, and amosite lower toxicity than crocidolite. The last decades of the twentieth century saw stabilisation and/or declines in mesothelioma rates in several industrialised countries. In less-industrialised countries, data on disease are sparse, exposure generally high and rates may peak in the future. Management of asbestos-related disease in the workplace requires collaboration between workers and unions (responsible for monitoring workplace dust levels, to which they must have access) and companies (responsible for engineering controls), reinforced by appropriate government regulations and by community support.}, } @article {pmid17393919, year = {2007}, author = {Carbone, M and Strianese, O and Theos, K and Yang, H}, title = {Mesothelioma.}, journal = {Hawaii medical journal}, volume = {66}, number = {2}, pages = {48-50}, pmid = {17393919}, issn = {0017-8594}, support = {R01 CA092657/CA/NCI NIH HHS/United States ; }, mesh = {Asbestos/toxicity ; Compensation and Redress ; Humans ; *Mesothelioma/diagnosis/economics/etiology/therapy ; Peritoneal Neoplasms/diagnosis/economics/etiology/therapy ; Pleural Neoplasms/diagnosis/economics/etiology/therapy ; Public Health Administration ; }, abstract = {Mesothelioma is one of the most aggressive human malignancies. In this article the research team of Dr. Michele Carbone reviewed the most significant scientific and medical advances in understanding the pathogenesis of mesothelioma and some novel preventive and therapeutic approaches that are being developed. The public health and litigation issues, together with the economics surrounding mesothelioma research and therapy are also discussed.}, } @article {pmid17393666, year = {2006}, author = {Proietti, L and Spicuzza, L and Di Maria, A and Polosa, R and Sebastian Torres, E and Asero, V and Di Maria, GU}, title = {Non-occupational malignant pleural mesothelioma due to asbestos and non-asbestos fibres.}, journal = {Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace}, volume = {65}, number = {4}, pages = {210-216}, doi = {10.4081/monaldi.2006.551}, pmid = {17393666}, issn = {1122-0643}, mesh = {Asbestos/*adverse effects ; *Carcinogens ; Environmental Exposure/*adverse effects ; Epidemiologic Studies ; Genetic Predisposition to Disease ; Humans ; Mesothelioma/*chemically induced/epidemiology/pathology ; Mineral Fibers/*adverse effects ; Pleural Effusion, Malignant/*chemically induced/epidemiology/pathology ; Sicily/epidemiology ; }, abstract = {BACKGROUND AND AIM: The occurrence of malignant pleural mesothelioma (MPM) has been reported among population groups with no documented professional exposure to asbestos fibres living in different geographic areas. This paper reviews existing data related to non occupational MPM including its occurrence in the province of Catania (Sicily, Italy).

METHODS: An electronic search of literature related to non occupational MPM was performed including the year 2005.

RESULTS: Non occupational MPM in subjects living in areas contaminated by a variety of asbestos and non asbestos fibres has been well documented through a number of epidemiologic studies including cases series, case-control studies, and a cohort study. In addition, the observation of familial clustering of MPM, suggests that genetic factors may play a role in the pathogenesis of this malignancy. The epidemiological evidence also suggests that MPM may occur as a result of the interaction between environmental carcinogens, genetic factors, and virus infection.

CONCLUSION: It is likely that genetic predisposition and non-occupational exposure to low doses of asbestos and asbestos-like fibres may concur to the development of malignant mesothelioma. However, additional epidemiological and laboratory studies are needed to further understand the relationship between environmental exposure and individual susceptibility to this malignancy.}, } @article {pmid17388830, year = {2007}, author = {Bilgin, M and Hasdiraz, L and Ozkaya, M and Oguzkaya, F}, title = {Can serum inflammatory parameters estimate outcome of pleurodesis in mesothelioma?.}, journal = {ANZ journal of surgery}, volume = {77}, number = {4}, pages = {253-255}, doi = {10.1111/j.1445-2197.2007.04028.x}, pmid = {17388830}, issn = {1445-1433}, mesh = {*Blood Sedimentation ; C-Reactive Protein/analysis ; Female ; Humans ; Leukocyte Count ; Male ; Mesothelioma/*blood/*therapy ; Middle Aged ; Pleural Neoplasms/*blood/*therapy ; *Pleurodesis ; Predictive Value of Tests ; Prospective Studies ; Talc/*administration & dosage ; Thoracic Surgery, Video-Assisted ; Treatment Outcome ; }, abstract = {BACKGROUND: As pleurodesis causes systemic inflammation and is associated with considerable cost and morbidity during long-term follow up, the identification of patients who will experience an unsuccessful pleurodesis would be desirable. This study was aimed to investigate whether systemic inflammatory reaction induced by insuflation of talc into the pleura can predict the outcome of pleurodesis.

METHODS: A total of 58 consecutive patients (26 men, 32 women) with malignant pleural mesothelioma underwent video-assisted thoracoscopy under general anaesthesia with monopulmonary ventilation between the years 2003 and 2006. Four grammes of asbestos-free and sterile talc were insuflated into the pleural space under direct vision. To assess the success of pleurodesis, chest radiographs were obtained at the 8th and 30th postoperative days. Venous blood samples were drawn both on admission and at the 24th hour after pleurodesis for the analysis of white blood cells, erythrocyte sedimentation rate and C-reactive protein.

RESULTS: The mean age (standard deviation) of patients was 59.0 +/- 12.0 years. Pleurodesis was achieved (no effusion on chest radiograph) in 43 of 58 patients (74.1%)(group I), whereas it was unsuccessful in the remaining 15 patients (25.9%)(group II). There was a significant difference between two groups for basal and postpleurodesis levels of measured inflammatory parameters, C-reactive protein and erythrocyte sedimentation rate (for each, P < 0.05). However, the difference was not significant for white blood cells between the groups.

CONCLUSION: Serum levels of inflammatory parameters (C-reactive protein and erythrocyte sedimentation rate) may be used to predict the success of pleurodesis in patients with malign mesothelioma who underwent thoracoscopic talc poudrage.}, } @article {pmid17387504, year = {2007}, author = {De Zotti, R and Fiorito, A}, title = {A case of malignant mesothelioma in a rice-starch factory.}, journal = {International archives of occupational and environmental health}, volume = {80}, number = {8}, pages = {743-745}, pmid = {17387504}, issn = {0340-0131}, mesh = {Aged ; Asbestos/*toxicity ; Fatal Outcome ; Female ; *Food Packaging ; *Food-Processing Industry ; Humans ; Italy ; Medical History Taking ; Mesothelioma/*chemically induced ; Occupational Exposure/*adverse effects ; Oryza ; Pleural Neoplasms/*chemically induced ; Textiles/toxicity ; Workforce ; }, abstract = {INTRODUCTION: Recent reports of cases of malignant mesothelioma (MM) in "non-traditional" areas of employment are an indication of the numerous occasions in which exposure to asbestos has occurred in the workplace. We describe an unusual case of occupational exposure to asbestos to stress the importance of careful history taking when assessing a patient's work history, especially in generic occupations in which there is apparently no exposure to asbestos.

CASE REPORT: Malignant mesothelioma was diagnosed in a woman worker employed in a factory making rice starch. She had worked in the storehouse of the factory for approximately 40 years. From circumstantial interviews with relatives and workmates, it emerged that her job involved retrieving, for re-use, the jute sacks in which the rice was transported. More than one source remembered distinctly that some of the sacks had "Asbestos" written on the outside.

DISCUSSION: This case provides further confirmation of the importance of careful history taking among workers with mesothelioma to avoid failing to diagnose occupational disease. It also highlights the risk of asbestos exposure represented by recycling asbestos-contaminated sacks in both occupational and non-occupational settings.}, } @article {pmid17382808, year = {2007}, author = {Wagner, GR}, title = {The fallout from asbestos.}, journal = {Lancet (London, England)}, volume = {369}, number = {9566}, pages = {973-974}, doi = {10.1016/S0140-6736(07)60472-3}, pmid = {17382808}, issn = {1474-547X}, mesh = {Asbestos/*adverse effects ; Asbestosis/*etiology/mortality ; Global Health ; Humans ; Mesothelioma/*etiology/mortality ; Occupational Exposure/*adverse effects/economics/legislation & jurisprudence ; Time Factors ; }, } @article {pmid17382060, year = {2006}, author = {Hosny, G and Akel, M}, title = {Assessment of asbestos in drinking water in alexandria, egypt.}, journal = {The Journal of the Egyptian Public Health Association}, volume = {81}, number = {3-4}, pages = {181-198}, pmid = {17382060}, issn = {0013-2446}, abstract = {Over the past several years, the presence of fibrous asbestos particulates has been observed in a number of municipal water supplies throughout the USA, Canada, and several other regions all over the world. The possible health hazards which these fibers present have spurred a great deal of interest in the problems of detection and removal of the submicroscopic particulates in water. Asbestos is a group of fibrous metamorphic silicate minerals that is ubiquitous in the environment as a result of its extensive industrial use and the dissemination of fibers from natural sources. The health hazards associated with inhalation of asbestos in the occupational environment have long been recognized including asbestosis, bronchial carcinoma, malignant mesothelioma of the pleura and peritoneum, and possibly cancers of the gastrointestinal tract and larynx. It is introduced into water by the dissolution of asbestos-containing minerals and ores, and from industrial effluents, atmospheric pollution and erosion of asbestos-cement (A/C) pipes in the distribution systems of drinking water. In Alexandria, most of the pipes in the distribution systems of drinking water are asbestos-cement (A/C) pipe system. Drinking water samples (1 liter each) were collected in glass containers from different regions in Alexandria and filtered in cellulose filters (mixed cellulose ester type filters of pore size 0.2 mum) within less than 48 hours. Filters were allowed to dry, gold plated and scanned microscopically. Asbestos fibers were detected in all water samples collected from regions having A/C pipe drainage system. No fibers detected in regions, where the pipe distribution system was poly venyl pipe system or changed from A/C pipe to cast iron pipe system. The determination of asbestos fibers in drinking water of Alexandria should have particular concern because of the health hazards that might be associated with their presence.}, } @article {pmid17375514, year = {2007}, author = {O'Reilly, KM and Mclaughlin, AM and Beckett, WS and Sime, PJ}, title = {Asbestos-related lung disease.}, journal = {American family physician}, volume = {75}, number = {5}, pages = {683-688}, pmid = {17375514}, issn = {0002-838X}, support = {P30 ES01247/ES/NIEHS NIH HHS/United States ; }, mesh = {Asbestos/*adverse effects ; Asbestosis/etiology ; Carcinogens/*toxicity ; Humans ; Lung Diseases/*etiology ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Occupational Diseases/*etiology ; Occupational Exposure/*adverse effects ; Pleural Diseases/etiology ; }, abstract = {The inhalation of asbestos fibers may lead to a number of respiratory diseases, including lung cancer, asbestosis, pleural plaques, benign pleural effusion, and malignant mesothelioma. Although exposure is now regulated, patients continue to present with these diseases because of the long latent period between exposure and clinical disease. Presenting signs and symptoms tend to be nonspecific; thus, the occupational history helps guide clinical suspicion. High-risk populations include persons in construction trades, boilermakers, shipyard workers, railroad workers, and U.S. Navy veterans. Every effort should be made to minimize ongoing exposure. Patients with a history of significant asbestos exposure may warrant diagnostic testing and follow-up assessment, although it is unclear whether this improves outcomes. Patients with significant exposure and dyspnea should have chest radiography and spirometry. The prognosis depends on the specific disease entity. Asbestosis generally progresses slowly, whereas malignant mesothelioma has an extremely poor prognosis. The treatment of patients with asbestos exposure and lung cancer is identical to that of any patient with lung cancer. Because exposure to cigarette smoke increases the risk of developing lung cancer in patients with a history of asbestos exposure, smoking cessation is essential. Patients with asbestosis or lung cancer should receive influenza and pneumococcal vaccinations.}, } @article {pmid17370376, year = {2006}, author = {Pairon, JC and Jaurand, MC and Laurent, F and Salmi, R and Astoul, P and Galateau-Sallé, F and Brochard, P}, title = {[How to assess asbestos exposure and identify a population at risk?].}, journal = {Revue des maladies respiratoires}, volume = {23}, number = {4 Pt 3}, pages = {11S9-27}, pmid = {17370376}, issn = {0761-8425}, mesh = {Asbestos/*adverse effects ; *Carcinogens ; *Environmental Exposure ; Humans ; Mesothelioma/*diagnosis/etiology ; *Occupational Exposure ; Pleural Neoplasms/*diagnosis/etiology ; Risk Factors ; }, } @article {pmid17365079, year = {2007}, author = {Dönmez-Altuntas, H and Baran, M and Oymak, FS and Hamurcu, Z and Imamoğlu, N and Ozesmi, M and Demirtas, H}, title = {Investigation of micronucleus frequencies in lymphocytes of inhabitants environmentally exposed to chrysotile asbestos.}, journal = {International journal of environmental health research}, volume = {17}, number = {1}, pages = {45-51}, doi = {10.1080/09603120601124231}, pmid = {17365079}, issn = {0960-3123}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos, Serpentine/*toxicity ; Carcinogens/*toxicity ; Cells, Cultured ; Environmental Exposure ; Female ; Humans ; Lymphocytes/*drug effects ; Male ; *Micronuclei, Chromosome-Defective ; Micronucleus Tests ; Middle Aged ; Turkey/epidemiology ; }, abstract = {Exposure to asbestos minerals has been associated with a wide variety of adverse health effects including lung cancer, pleural mesothelioma, and cancer of other organs. Many of the regions of Turkey have asbestos deposits. People in Doğanli village - one of these regions - have been environmentally exposed to chrysotile asbestos since they were born. In this study the effects of asbestos on micronucleus (MN) frequencies of inhabitants exposed to chrysotile asbestos have been examined. Thirty subjects who had been environmentally exposed to chrysotile asbestos and living in Doğanli village, and 25 controls were studied to assess the MN frequency. The control group was selected from healthy individuals with no exposure to asbestos and living in similar geographic conditions to Doğanli village. Peripheral blood samples were collected from each subject and cultured for MN assay. Cytochalasin-B was added to lymphocyte cultures for evaluation of MN in binucleated (BN) cells. The differences between those exposed to chrysotile asbestos and controls were not statistically significant in terms of BN cells with MN (p > 0.05). There was not a significant relationship between MN frequencies and age, sex, smoking, both in chrysotile asbestos-exposed subjects and in controls (p > 0.05). Although the detection of calcified pleural plaques found in the inhabitants has indicated environmental exposure to chrysotile asbestos, our results show that chrysotile asbestos was not an inducer of MN in subjects exposed to chrysotile asbestos.}, } @article {pmid17363104, year = {2007}, author = {Demirag, F and Unsal, E and Tastepe, I}, title = {Biphasic malignant mesothelioma cases with osseous differentiation and long survival: a review of the literature.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {57}, number = {2}, pages = {233-236}, doi = {10.1016/j.lungcan.2007.01.033}, pmid = {17363104}, issn = {0169-5002}, mesh = {Aged ; Asbestosis/complications/pathology ; Biomarkers, Tumor/metabolism ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Keratin-5/metabolism ; Keratin-6/metabolism ; Male ; Mesothelioma/chemistry/diagnostic imaging/etiology/metabolism/*pathology ; Middle Aged ; *Ossification, Heterotopic ; Osteoclasts/metabolism ; Pleural Neoplasms/chemistry/diagnostic imaging/etiology/metabolism/*pathology ; Survival Analysis ; Time Factors ; Tomography, X-Ray Computed ; }, abstract = {This report describes two cases of diffuse biphasic malignant mesothelioma with osseous differentiation and long survival. Two male patients aged 66 and 54 years presented with chest pain, bloody pleural effusions, and diffuse and nodular pleural thickening. They both had a history of prolonged asbestos exposure. Sarcomatoid and epithelioid areas were identified on histopathological examination. In addition, there were foci of ossification. Epithelioid tumor cells as well as benign osteoclasts within the ossification reacted positively for cytokeratin 5/6, whereas sarcomatoid areas were negative. Both patients survived 39 and 69 months, respectively. To our knowledge, these two cases with biphasic malignant mesothelioma and osseous differentiation with long survival are the first to be described from Central Anatolia.}, } @article {pmid17356113, year = {2007}, author = {Patel, N and Bishay, A and Bakry, M and George, L and Saleh, A}, title = {Dyspnea with slow-growing mass of the left hemithorax.}, journal = {Chest}, volume = {131}, number = {3}, pages = {904-908}, doi = {10.1378/chest.06-0485}, pmid = {17356113}, issn = {0012-3692}, mesh = {Diagnosis, Differential ; Dyspnea/*etiology ; Humans ; Male ; Mesothelioma/*diagnostic imaging/pathology/surgery ; Pleural Neoplasms/*diagnostic imaging/pathology/surgery ; Tomography, X-Ray Computed ; }, abstract = {We report a case of a 65-year-old male patient who presented with gradually worsening dyspnea over 2 years. History was significant for smoking and the absence of any hazardous occupational exposure. The clinical findings at presentation included absent breath sounds and stony dullness on the left side, with tracheal deviation contralaterally and clubbing. A chest roentgenogram showed a left-sided opacity occupying almost the entire left hemithorax. A subsequent CT scan of the chest revealed an intrathoracic, extrapulmonary lesion producing a mediastinal shift. Surgical resection of the mass was performed, and pathology, along with immunohistochemical studies positive for CD34 and negative for epithelial markers, confirmed the diagnosis of solitary fibrous tumor of the pleura (SFTP). SFTP is a rare neoplasm, and diagnosis is often difficult. Suspicion of SFTP should arise in the setting of a patient presenting with a paucity of symptoms (except in the case of an accompanying paraneoplastic syndrome), the absence of exposure to asbestos, and a large mass with sharp margins and encapsulation seen on a chest radiograph.}, } @article {pmid17354240, year = {2007}, author = {Bertino, P and Marconi, A and Palumbo, L and Bruni, BM and Barbone, D and Germano, S and Dogan, AU and Tassi, GF and Porta, C and Mutti, L and Gaudino, G}, title = {Erionite and asbestos differently cause transformation of human mesothelial cells.}, journal = {International journal of cancer}, volume = {121}, number = {1}, pages = {12-20}, doi = {10.1002/ijc.22687}, pmid = {17354240}, issn = {0020-7136}, mesh = {Asbestos/*toxicity ; Cell Death/drug effects ; Cell Transformation, Neoplastic/*chemically induced ; Cells, Cultured ; Cytotoxins/toxicity ; DNA/biosynthesis/genetics ; DNA Damage/genetics ; Epithelium/*drug effects/*pathology ; Humans ; Microscopy, Electron, Scanning ; Time Factors ; Zeolites/*toxicity ; }, abstract = {Malignant mesothelioma (MM) is an aggressive tumor associated with environmental or occupational exposure to asbestos fibers. Erionite is a fibrous zeolite, morphologically similar to asbestos and it is assumed to be even more carcinogenic. Onset and progression of MM has been suggested as the result of the cooperation between asbestos and other cofactors, such as SV40 virus infection. Nevertheless, several cases of MM were associated with environmental exposure to erionite in Turkey, where SV40 was never isolated in MM specimens. We show here that erionite is poorly cytotoxic, induces proliferating signals and high growth rate in human mesothelial cells (HMC). Long term exposure to erionite, but not to asbestos fibers, transforms HMC in vitro, regardless of the presence of SV40 sequences, leading to foci formation in cultured monolayers. Cells derived from foci display constitutive activation of Akt, NF-kappaB and Erk1/2, show prolonged survival and a deregulated cell cycle, involving cyclin D1 and E overexpression. Our results reveal that erionite is able per se to turn HMC into transformed highly proliferating cells and disclose the carcinogenic properties of erionite, prompting for a careful evaluation of environmental exposure to these fibers. The genetic predisposition to the effect of erionite is a separate subject for investigation.}, } @article {pmid17350855, year = {2007}, author = {Opitz, I and Lardinois, D and Arni, S and Hillinger, S and Vogt, P and Odermatt, B and Rousson, V and Weder, W}, title = {Local recurrence model of malignant pleural mesothelioma for investigation of intrapleural treatment.}, journal = {European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery}, volume = {31}, number = {5}, pages = {773-778}, doi = {10.1016/j.ejcts.2007.01.047}, pmid = {17350855}, issn = {1010-7940}, mesh = {Animals ; Anti-Infective Agents, Local/therapeutic use ; Antineoplastic Agents/therapeutic use ; Cell Line, Tumor ; Chemokine CCL19 ; Chemokines, CC/therapeutic use ; Cisplatin/therapeutic use ; Combined Modality Therapy/methods ; *Disease Models, Animal ; Fibrin Tissue Adhesive/therapeutic use ; Male ; Mesothelioma/*drug therapy/surgery ; Neoplasm Recurrence, Local/*drug therapy/surgery ; Pleural Neoplasms/*drug therapy/surgery ; Pneumonectomy/methods ; Povidone-Iodine/therapeutic use ; Rats ; Rats, Inbred F344 ; Taurine/analogs & derivatives/therapeutic use ; Thiadiazines/therapeutic use ; }, abstract = {OBJECTIVE: Local recurrence remains a major problem in the treatment of malignant pleural mesothelioma. The aim of the underlying study was to establish a standardised local recurrence model in rats which enables to study different intrapleural therapies.

MATERIALS AND METHODS: Fifty microlitre containing 1 x 10(6) cells of a syngeneic rat malignant mesothelioma cell line (II-45), established from mesothelioma in Fischer 344 rats exposed to asbestos, were inoculated subpleurally via a left-sided thoracotomy. Tumour size was assessed 6 days later and the tumour nodule completely resected. Evaluation of recurrence at the resection site was performed after 10 days (n=6) and 6 days (n=6). The recurrent nodule was histopathologically confirmed. In a second experiment, this new recurrence model was evaluated for the effect of intrapleural therapy with different agents: 4 ml of cisplatin-solution (100mg(2)/kg BW), cisplatin combined with the fibrin-based sealant Vivostat, 4 ml taurolidine 2%, repeated injection of 1 microg of the chemokine CCL-19 at the tumour site and 4 ml povidone-iodine in a dilution 1:10. In a control group, the chest cavity was filled with 4 ml 0.9% NaCl. The primary endpoint was the extent of tumour recurrence.

RESULTS: Six days after inoculation, all animals presented a standardised tumour nodule at the injection site of a mean diameter of 5.1 (+/-0.8)mm. Evaluation of the recurrence after 10 days showed a relapse directly at the resection site, but additional tumour nodules on the ipsi- and contralateral chest wall were found and histologically confirmed. The animals that were sacrificed 6 days after resection of the tumour nodule showed a recurrence only at the resection site with no macroscopic or microscopic evidence of other tumour. Resection of the tumour nodule combined with intrapleural application of the different agents lead to clear reduction of recurrence. The strongest effect was observed after intrapleural application of cisplatin-Vivostat with significant decrease of the longest, widest and thickest diameter of the recurrence.

CONCLUSIONS: With this new recurrence model for investigation of malignant pleural mesothelioma in rats, we were able to investigate new intrapleural therapies after pneumonectomy. The intrapleural application of cisplatin-Vivostat significantly reduced the extent of local recurrence.}, } @article {pmid17350453, year = {2007}, author = {Lin, RT and Takahashi, K and Karjalainen, A and Hoshuyama, T and Wilson, D and Kameda, T and Chan, CC and Wen, CP and Furuya, S and Higashi, T and Chien, LC and Ohtaki, M}, title = {Ecological association between asbestos-related diseases and historical asbestos consumption: an international analysis.}, journal = {Lancet (London, England)}, volume = {369}, number = {9564}, pages = {844-849}, doi = {10.1016/S0140-6736(07)60412-7}, pmid = {17350453}, issn = {1474-547X}, mesh = {Asbestosis/*history/*mortality ; Environmental Exposure/*history/*statistics & numerical data ; Female ; Global Health ; History, 20th Century ; History, 21st Century ; Humans ; Male ; Mesothelioma/history/mortality ; Peritoneal Neoplasms/history/mortality ; Regression Analysis ; Sex Distribution ; }, abstract = {BACKGROUND: The potential for a global epidemic of asbestos-related diseases is a growing concern. Our aim was to assess the ecological association between national death rates from diseases associated with asbestos and historical consumption of asbestos.

METHODS: We calculated, for all countries with data, yearly age-adjusted mortality rates by sex (deaths per million population per year) for each disease associated with asbestos (pleural, peritoneal, and all mesothelioma, and asbestosis) in 2000-04 and mean per head asbestos consumption (kg per person per year) in 1960-69. We regressed death rates for the specified diseases against historical asbestos consumption, weighted by the size of sex-specific national populations.

FINDINGS: Historical asbestos consumption was a significant predictor of death for all mesothelioma in both sexes (adjusted R2=0.74, p<0.0001, 2.4-fold [95% CI 2.0-2.9] mortality increase was predicted per unit consumption increase for men; 0.58, p<0.0001, and 1.6-fold [1.4-1.9] mortality increase was predicted for women); for pleural mesothelioma in men (0.29, p=0.0015, 1.8-fold [1.3-2.5]); for peritoneal mesothelioma in both sexes (0.54, p<0.0001, 2.2-fold [1.6-2.9] for men, 0.35, p=0.0008, and 1.4-fold for women [1.2-1.6]); and for asbestosis in men (0.79, p<0.0001, 2.7-fold [2.2-3.4]). Linear regression lines consistently had intercepts near zero.

INTERPRETATION: Within the constraints of an ecological study, clear and plausible associations were shown between deaths from the studied diseases and historical asbestos consumption, especially for all mesothelioma in both sexes and asbestosis in men. Our data strongly support the recommendation that all countries should move towards eliminating use of asbestos.}, } @article {pmid17344668, year = {2006}, author = {Maeda, M and Hino, O}, title = {Blood tests for asbestos-related mesothelioma.}, journal = {Oncology}, volume = {71}, number = {1-2}, pages = {26-31}, doi = {10.1159/000100446}, pmid = {17344668}, issn = {0030-2414}, mesh = {Asbestos/*toxicity ; Biomarkers, Tumor/blood ; Blood Proteins/analysis ; Carcinogens/*toxicity ; *Enzyme-Linked Immunosorbent Assay ; GPI-Linked Proteins ; Humans ; Membrane Glycoproteins/*blood ; Mesothelin ; Mesothelioma/*blood/diagnosis/etiology ; Oncogene Proteins/*blood ; Pleural Neoplasms/*blood/diagnosis/etiology ; }, abstract = {Mesothelioma is an aggressive tumor arising from the mesothelium, and is usually associated with previous exposure to asbestos. The incubation period of the tumor may be described as 30-40 years, and the prognosis is dismal. Recently, serum markers for the diagnosis of mesothelioma have been reported as candidates. In this paper, we mini-reviewed the potential utility of ELISA systems as serum diagnostic markers for asbestos-related mesothelioma.}, } @article {pmid17333692, year = {2006}, author = {Chiappino, G}, title = {[Asbestos fibre dimensions and mesothelioma].}, journal = {Epidemiologia e prevenzione}, volume = {30}, number = {6}, pages = {358-60; discussion 361, 369}, pmid = {17333692}, issn = {1120-9763}, mesh = {Asbestos/*adverse effects ; Environmental Exposure ; Humans ; Italy ; Mesothelioma/*etiology/*prevention & control ; Microscopy, Electron ; Mineral Fibers/adverse effects ; Particle Size ; Pleural Neoplasms/*etiology/*prevention & control ; }, abstract = {The critical considerations formulated by Tomatis et al. did not take into account all the experimental works and all the research on human pleura that from the Seventies on has unanimously indicated that asbestos fibre mesothelioma is caused by the ultrafine fibres class. These fibres that are so fine are not visible with light microscopy are mostly ultrashort, but they also include, in varying percentages, elements that are >5 microm long. The conclusions of Tomatis et al, which attribute mesothelioma to fibres of all lengths and diameters, are not confirmed in the literature. Today, mesothelioma prevention must consist of identifying and cutting down airborne ultrafine fibres, above all in urban environments. The techniques for doing so now exist and can be applied. The ultrafine class of asbestos, forgotten for decades, must be the principal target for prevention programs and must be widely monitored in work and daily life settings.}, } @article {pmid17331233, year = {2007}, author = {Nymark, P and Lindholm, PM and Korpela, MV and Lahti, L and Ruosaari, S and Kaski, S and Hollmén, J and Anttila, S and Kinnula, VL and Knuutila, S}, title = {Gene expression profiles in asbestos-exposed epithelial and mesothelial lung cell lines.}, journal = {BMC genomics}, volume = {8}, number = {}, pages = {62}, pmid = {17331233}, issn = {1471-2164}, mesh = {Asbestos, Crocidolite/*toxicity ; Cell Line ; Cluster Analysis ; Epithelium/*drug effects/metabolism ; *Gene Expression Profiling ; Humans ; Lung/cytology/*drug effects/metabolism ; Lung Diseases/chemically induced ; Nucleic Acid Hybridization ; }, abstract = {BACKGROUND: Asbestos has been shown to cause chromosomal damage and DNA aberrations. Exposure to asbestos causes many lung diseases e.g. asbestosis, malignant mesothelioma, and lung cancer, but the disease-related processes are still largely unknown. We exposed the human cell lines A549, Beas-2B and Met5A to crocidolite asbestos and determined time-dependent gene expression profiles by using Affymetrix arrays. The hybridization data was analyzed by using an algorithm specifically designed for clustering of short time series expression data. A canonical correlation analysis was applied to identify correlations between the cell lines, and a Gene Ontology analysis method for the identification of enriched, differentially expressed biological processes.

RESULTS: We recognized a large number of previously known as well as new potential asbestos-associated genes and biological processes, and identified chromosomal regions enriched with genes potentially contributing to common responses to asbestos in these cell lines. These include genes such as the thioredoxin domain containing gene (TXNDC) and the potential tumor suppressor, BCL2/adenovirus E1B 19kD-interacting protein gene (BNIP3L), GO-terms such as "positive regulation of I-kappaB kinase/NF-kappaB cascade" and "positive regulation of transcription, DNA-dependent", and chromosomal regions such as 2p22, 9p13, and 14q21. We present the complete data sets as Additional files.

CONCLUSION: This study identifies several interesting targets for further investigation in relation to asbestos-associated diseases.}, } @article {pmid17322126, year = {2007}, author = {Riganti, C and Orecchia, S and Silvagno, F and Pescarmona, G and Betta, PG and Gazzano, E and Aldieri, E and Ghigo, D and Bosia, A}, title = {Asbestos induces nitric oxide synthesis in mesothelioma cells via Rho signaling inhibition.}, journal = {American journal of respiratory cell and molecular biology}, volume = {36}, number = {6}, pages = {746-756}, doi = {10.1165/rcmb.2006-0011OC}, pmid = {17322126}, issn = {1044-1549}, mesh = {Active Transport, Cell Nucleus/physiology ; Amides/metabolism ; Animals ; Asbestos, Crocidolite/*metabolism ; Cattle ; Cell Line, Tumor ; Enzyme Activation ; Enzyme Induction ; Enzyme Inhibitors/metabolism ; Humans ; I-kappa B Kinase/metabolism ; Isoenzymes/antagonists & inhibitors/metabolism ; Lovastatin/analogs & derivatives/metabolism ; Mesothelioma/*metabolism/pathology ; Mevalonic Acid/metabolism ; NF-kappa B/metabolism ; Nitric Oxide/*biosynthesis ; Nitric Oxide Synthase/antagonists & inhibitors/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Pyridines/metabolism ; Second Messenger Systems/*physiology ; Terpenes/metabolism ; rho GTP-Binding Proteins/*metabolism ; }, abstract = {We have observed that in three human malignant mesothelioma cell lines, crocidolite asbestos induced the activation of the transcription factor NF-kappaB and the synthesis of nitric oxide (NO) by inhibiting the RhoA signaling pathway. The incubation with crocidolite decreased the level of GTP-bound RhoA and the activity of Rho-dependent kinase, and induced the activation of Akt/PKB and IkBalpha kinase, leading to the nuclear translocation of NF-kappaB. The effects of crocidolite fibers on NF-kappaB activation and NO synthesis were mimicked by Y27632 (an inhibitor of the Rho-dependent kinases) and toxin B (an inhibitor of RhoA GTPase activity), while they were reverted by mevalonic acid, the product of 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase. Furthermore, crocidolite, similarly to mevastatin, inhibited the synthesis of cholesterol and ubiquinone and the prenylation of RhoA: these effects were prevented in the presence of mevalonic acid. This suggests that crocidolite fibers might inhibit the synthesis of isoprenoid molecules at the level of the HMGCoA reductase reaction or of an upstream step, thus impairing the prenylation and subsequent activation of RhoA. Akt can stimulate NO synthesis via a double mechanism: it can activate the inducible NO synthase via the NF-kappaB pathway and the endothelial NO synthase via a direct phosphorylation. Our results suggest that crocidolite increases the NO levels in mesothelioma cells by modulating both NO synthase isoforms.}, } @article {pmid17321072, year = {2007}, author = {Baumann, F and Rougier, Y and Ambrosi, JP and Robineau, BP}, title = {Pleural mesothelioma in New Caledonia: an acute environmental concern.}, journal = {Cancer detection and prevention}, volume = {31}, number = {1}, pages = {70-76}, doi = {10.1016/j.cdp.2006.10.009}, pmid = {17321072}, issn = {0361-090X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Air Pollutants/adverse effects ; Analysis of Variance ; Asbestos, Serpentine/adverse effects ; Case-Control Studies ; Environmental Exposure/*adverse effects ; Female ; Humans ; Male ; Mesothelioma/*epidemiology/ethnology/*etiology ; Middle Aged ; Mining ; New Caledonia/epidemiology ; Pleural Neoplasms/*epidemiology/ethnology/*etiology ; Registries ; Regression Analysis ; Residence Characteristics ; Risk Factors ; Soil ; }, abstract = {BACKGROUND: In 1991, a relationship was established between excess cases of pleural cancer in New Caledonia and a traditional lime, called "Pö", to cover houses. Our study aimed to determine whether the Pö is the only cause of mesothelioma in New Caledonia.

METHODS: Eligible cases were pleural tumor diagnosed between 1984 and 2002 with histological diagnosis of mesothelioma. For each case, two controls were selected from the cancer registry. Cases and controls were compared for the ethnic groups and the places of residence. To identify environmental risk factors, we used first a qualitative analysis comparing villages with and without mesothelioma cases, then a linear regression including Pö, mining activity and serpentinite in surface soil.

RESULTS: Sixty-eight cases were included: 37 men and 31 women. Melanesians had the highest risk (OR=16.18; 95% CI=[5.68; 49.64]) and 30% of the cases lived in Houailou (OR=119). Mining activity and Pö were not significant risk factors. The existence of a significant relationship between soil containing serpentinite and mesothelioma was demonstrated (p=0.017). The sex ratio close to 1 and the number of young cases are consistent with environmental exposure.

CONCLUSION: Pö did not explain all cases; only serpentinite in the soil was identified as a significant risk factor. A research project has been initiated in the area around Houailou, with the objective of constructing a model taking into account: exposure to the Pö, exposure to airborne pollution by asbestos fibres at the place of residence, and occupational exposure. Epidemiological and geological investigations are underway.}, } @article {pmid17306123, year = {2007}, author = {Gómez Portilla, A and Cendoya, I and Muriel, J and Olabarria, I and Guede, N and Moraza, N and Fernández, E and Martínez de Lecea, C and Magrach, L and Martín, E and Romero, E and Aguado, I and Valdovinos, M and Larrabide, I}, title = {[Malignant peritoneal mesothelioma. Our experienced with triple combined therapy: cytoreduction, intraperitoneal perioperative chemotherapy and hyperthermia].}, journal = {Cirugia espanola}, volume = {81}, number = {2}, pages = {82-86}, doi = {10.1016/s0009-739x(07)71268-x}, pmid = {17306123}, issn = {0009-739X}, mesh = {Adult ; Combined Modality Therapy ; Female ; Humans ; Hyperthermia, Induced ; Male ; Mesothelioma/drug therapy/surgery/*therapy ; Middle Aged ; Peritoneal Neoplasms/drug therapy/surgery/*therapy ; }, abstract = {INTRODUCTION: Malignant peritoneal mesothelioma is the most common primary neoplasm of the serous peritoneum. Most patients die of the complications of local disease confined to the peritoneal cavity, while nodal or distant dissemination is extremely rare. Prognosis with traditional therapeutic options is dismal, with a median survival of between 4 and 12 months from diagnosis. The application of a new combined therapy with cytoreductive surgery, intraperitoneal perioperative chemotherapy and heated intraperitoneal intraoperative chemotherapy, followed by early postoperative intraperitoneal chemotherapy is currently providing good results, in some instances even allowing curative intent. We present a series of patients treated with this triple combined therapy.

MATERIAL AND METHOD: Between December 1998 and December 2005, 78 cytoreductive surgeries were performed in 50 patients in our peritoneal carcinomatosis program at the San Jose Policlinic in Vitoria (Spain), for distinct reasons. Among these patients, surgery was performed on 11 occasions in seven patients with a diffuse malignant peritoneal mesothelioma. The present study focuses on this latter group of seven patients.

RESULTS: Eleven cytoreductions were performed in seven patients with diffuse malignant peritoneal mesothelioma. There were four men and three women, with a mean age of 50 years (range 31-57 years). None of the patients had a history of occupational exposure to asbestos or contact with this substance. All the patients had received more than one surgical intervention before entering our program. Only two patients had also received systemic chemotherapy as adjuvant treatment after their initial diagnosis, as the only possible therapeutic alternative. Treatment with curative intent was provided, obtaining complete cytoreduction of macroscopic disease in all patients, followed by application of intraperitoneal perioperative chemotherapy for the treatment of any residual microscopic disease. Pathologic analysis showed biphasic sarcomatous mesothelioma in two patients and epithelial mesothelioma in the remaining five patients. Postoperative complications occurred in five patients, resulting in a mean length of postoperative hospital stay of 41.5 days (range 17-84 days). Three patients died from disease progression at 3, 9 and 11 months after the initial cytoreduction; of these, two patients had diffuse biphasic sarcomatous mesothelioma. The remaining four patients are still alive at 5, 9, 19 and 54 months after the initial cytoreduction without evidence of disease at the present time.

CONCLUSIONS: Radical oncologic cytoreductive surgery combined with intraperitoneal perioperative chemotherapy provides good results with prolonged survival in selected cases, although morbidity is high. Based in our experience, biphasic sarcomatous mesotheliomas should be excluded from this protocol because of their aggressiveness; these tumors should be included only in conventional therapeutic strategies with palliative intent.}, } @article {pmid17296636, year = {2007}, author = {Reid, A and Berry, G and de Klerk, N and Hansen, J and Heyworth, J and Ambrosini, G and Fritschi, L and Olsen, N and Merler, E and Musk, AW}, title = {Age and sex differences in malignant mesothelioma after residential exposure to blue asbestos (crocidolite).}, journal = {Chest}, volume = {131}, number = {2}, pages = {376-382}, doi = {10.1378/chest.06-1690}, pmid = {17296636}, issn = {0012-3692}, mesh = {Age Factors ; Asbestos, Crocidolite/*toxicity ; Carcinogens/*toxicity ; Cohort Studies ; Environmental Exposure/*adverse effects ; Female ; Humans ; Incidence ; Male ; Mesothelioma/*epidemiology ; Mining ; Residence Characteristics ; Sex Factors ; Survival Rate ; Western Australia ; }, abstract = {BACKGROUND: Blue asbestos was mined and milled at Wittenoom, Western Australia, from 1943 until 1966. Various public records were used to establish a cohort of residents of the nearby township. Mine tailings were distributed throughout the town.

AIMS: To report the incident number of malignant mesotheliomas that have occurred in residents of the town who did not work at the mine or mill; and to determine if female subjects are more susceptible to asbestos exposure than male subjects, and if children are more susceptible than adults.

SUBJECTS AND METHODS: A total of 4,768 residents of the town of Wittenoom have been followed up in cancer and death registries.

RESULTS: There were 67 cases of mesothelioma, and 64 deaths with mesothelioma to the end of 2002. The mortality rate with mesothelioma increased with increasing residence duration, time since first exposure, and estimated cumulative exposure. The mesothelioma mortality rate was consistently lower for female subjects when compared with male subjects, but the dose-response curve was steeper for female subjects. The rate was lower in those first exposed as children compared with those first exposed at > or = 15 years of age. The dose-response slope for asbestos exposure and mortality from mesothelioma was not different between those who were first exposed as children than those who were first exposed at > or = 15 years of age.

CONCLUSIONS: Former residents of a crocidolite mining town have a high rate of mesothelioma. The rate is higher in male subjects and those > or = 15 years of age at first exposure, but women have a steeper dose-response curve.}, } @article {pmid17296628, year = {2007}, author = {Roggli, VL}, title = {Environmental asbestos contamination: What are the risks?.}, journal = {Chest}, volume = {131}, number = {2}, pages = {336-338}, doi = {10.1378/chest.06-2649}, pmid = {17296628}, issn = {0012-3692}, mesh = {Asbestos/*toxicity ; Carcinogens/*toxicity ; Environmental Exposure/*adverse effects ; Humans ; Maximum Allowable Concentration ; Mesothelioma/*etiology ; Risk Assessment ; }, } @article {pmid17294804, year = {2006}, author = {Edakuni, N and Ikuta, K and Yano, S and Nakataki, E and Muguruma, H and Uehara, H and Tani, M and Yokota, J and Aizawa, H and Sone, S}, title = {Restored expression of the MYO18B gene suppresses orthotopic growth and the production of bloody pleural effusion by human malignant pleural mesothelioma cells in SCID mice.}, journal = {Oncology research}, volume = {16}, number = {5}, pages = {235-243}, doi = {10.3727/000000006783981062}, pmid = {17294804}, issn = {0965-0407}, mesh = {Animals ; Apoptosis/drug effects ; Cell Growth Processes/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Disease Models, Animal ; Gene Expression Regulation, Neoplastic/*genetics ; Humans ; Lung Neoplasms/drug therapy/*genetics/metabolism ; Male ; Mesothelioma/drug therapy/*genetics/metabolism ; Mice ; Mice, SCID ; Myosins/*genetics/metabolism/*pharmacology ; Neoplasms, Experimental/genetics/metabolism/pathology ; Pleural Effusion/*genetics/metabolism ; Pleural Neoplasms/drug therapy/*genetics/metabolism ; Tumor Suppressor Proteins/*genetics/metabolism/*pharmacology ; Xenograft Model Antitumor Assays ; }, abstract = {Malignant pleural mesothelioma (MPM) is closely related to exposure to asbestos, and a rapid increase in the number of MPM patients is therefore estimated to occur from 2010 to 2040 in Japan. Because MPM is refractory to conventional chemotherapy and radiotherapy, the prognosis of MPM patients is extremely poor. MYO18B, a novel member of the myosin family, is a tumor suppressor gene isolated from a homozygously deleted region at 22q12.1 in a lung cancer cell line. The inactivation of the MYO18B gene plays an important role in several malignant diseases. However, the role of MYO18B in the progression of MPM is still unknown. Six different human MPM cell lines were used in this study. Western blot revealed that none of the cell lines expressed a detectable level of MYO18B protein. One of the MPM cell lines, EHMES-10, was transfected with the MYO18B gene. We found that a restored expression of the MYO18B protein in EHMES-10 cells resulted in the inhibition of their anchorage-independent growth and motility in vitro. In addition, it also inhibited their ectopic (subcutaneous space) and orthotopic (thoracic cavity) growth in SCID mice, in association with an increased degree of cell apoptosis. Furthermore, it also suppressed the production of bloody pleural effusion after orthotopic injection. These findings suggest that the restored expression of MYO18B may be a useful therapeutic strategy for the treatment of locally advanced MPM in humans.}, } @article {pmid17293641, year = {2007}, author = {van Brakel, J and van Ouwerkerk, B and Cleophas, TJ}, title = {Mesothelioma: a case report.}, journal = {The Netherlands journal of medicine}, volume = {65}, number = {1}, pages = {43; autho reply 43}, pmid = {17293641}, issn = {0300-2977}, mesh = {Abdominal Neoplasms/*diagnosis/etiology ; Adult ; Aged ; Asbestos/adverse effects ; Humans ; Male ; Mesothelioma/*diagnosis/etiology ; Occupational Exposure ; }, } @article {pmid17290392, year = {2007}, author = {Landi, S and Gemignani, F and Neri, M and Barale, R and Bonassi, S and Bottari, F and Canessa, PA and Canzian, F and Ceppi, M and Filiberti, R and Ivaldi, GP and Mencoboni, M and Scaruffi, P and Tonini, GP and Mutti, L and Puntoni, R}, title = {Polymorphisms of glutathione-S-transferase M1 and manganese superoxide dismutase are associated with the risk of malignant pleural mesothelioma.}, journal = {International journal of cancer}, volume = {120}, number = {12}, pages = {2739-2743}, doi = {10.1002/ijc.22590}, pmid = {17290392}, issn = {0020-7136}, mesh = {Aged ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Glutathione Transferase/*genetics ; Humans ; Logistic Models ; Male ; Mesothelioma/enzymology/genetics/*pathology ; Middle Aged ; Odds Ratio ; Pleural Neoplasms/genetics/*pathology ; *Polymorphism, Single Nucleotide ; Risk Factors ; Superoxide Dismutase/*genetics ; }, abstract = {Individual response to oxidative stress, due to exposure to asbestos fibres plays a significant role in the malignant pleural mesothelioma (MPM) etiology. The differential impact on MPM risk of polymorphic alleles of glutathione-S-transferases (GSTs) and manganese superoxide dismutase (MnSOD/SOD2) genes involved in the defence against oxidative damage has been investigated. Ninety cases of MPM and 395 controls were genotyped using the arrayed-primer extension technique. Logistic regression analysis was applied to assess the predictive role of single nucleotide polymorphisms (SNPs) potentially involved in MPM carcinogenesis after adjustment for potential confounders. An increased risk of MPM was found in subjects bearing a GSTM1 null allele (OR = 1.69, 95% CI = 1.04-2.74; p = 0.034), and in those with the Ala/Ala genotypes at codon 16 within MnSOD (OR = 3.07, 95% CI = 1.55-6.05; p = 0.001). A stronger effect of MnSOD was observed among patients without a clear exposure to asbestos fibres. No effect was found for GSTA2, GSTA4, GSTM3, GSTP1 and GSTT1 genes. These findings, if replicated, contribute substantial evidence to the hypothesis that oxidative stress and cellular antireactive oxygen species systems are involved in the pathogenesis and in the natural history of MPM.}, } @article {pmid17289801, year = {2007}, author = {Beyer, HL and Geschwindt, RD and Glover, CL and Tran, L and Hellstrom, I and Hellstrom, KE and Miller, MC and Verch, T and Allard, WJ and Pass, HI and Sardesai, NY}, title = {MESOMARK: a potential test for malignant pleural mesothelioma.}, journal = {Clinical chemistry}, volume = {53}, number = {4}, pages = {666-672}, doi = {10.1373/clinchem.2006.079327}, pmid = {17289801}, issn = {0009-9147}, mesh = {Biomarkers, Tumor/*blood ; Enzyme-Linked Immunosorbent Assay ; Female ; GPI-Linked Proteins ; Humans ; Male ; Membrane Glycoproteins/*blood ; Mesothelin ; Mesothelioma/*diagnosis ; Peptides/*blood ; Pleural Neoplasms/*diagnosis ; ROC Curve ; Reference Values ; Reproducibility of Results ; Sensitivity and Specificity ; Solubility ; }, abstract = {BACKGROUND: Soluble mesothelin-related peptides (SMRP)have been reported to be potential biomarkers for malignant pleural mesothelioma (MPM). We report analytical and preliminary clinical studies of MESOMARK, a quantitative assay for SMRP.

METHODS: The MESOMARK assay is a 2-step immunoenzymatic assay in an ELISA format with a 6-point calibration curve (0-32 nmol/L). We assessed analytical imprecision, analyte stability, and analytical interferences. We measured SMRP by this assay in 409 apparently healthy individuals (reference interval study), 177 patients with nonmalignant conditions, and 500 cancer patients, including 88 with MPM.

RESULTS: The limit of detection was 0.16 nmol/L. At 2-19 nmol/L, intraassay imprecision (CV) was 1.1%-5.3%, and total imprecision was 4.0%-11.0%. The mean dilution recovery for 5 samples was 109% (range, 99%-113%). No interference was seen from added bilirubin (200 mg/L), hemoglobin (500 mg/L), triglycerides (30 g/L), chemotherapeutic agents, or other tested substances. Recombinant mesothelin was stable in serum upon freeze/thaw at -70 degrees C and upon storage for at least 7 days at 2-8 degrees C. The 99(th) percentile of the reference group was 1.5 nmol/L [95% confidence interval (CI), 1.2-1.6 nmol/L; n = 409], and mean SMRP was significantly higher in sera from patients with MPM (7.5 nmol/L; 95% CI, 2.8-12.1 nmol/L; n = 88). SMRP was increased in 52% and 5% of MPM patients and asbestos-exposed individuals, respectively. Concentrations in other nonmalignant and malignant conditions were similar to those in healthy controls.

CONCLUSIONS: The MESOMARK assay is analytically robust and may be useful for the detection and management of mesothelioma.}, } @article {pmid17283842, year = {2006}, author = {Scripcariu, V and Dajbog, E and Lefter, L and Ferariu, D and Pricop, A and Grigoraş, M and Dragomir, C}, title = {[Malignant peritoneal mesothelioma].}, journal = {Chirurgia (Bucharest, Romania : 1990)}, volume = {101}, number = {6}, pages = {641-646}, pmid = {17283842}, issn = {1221-9118}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Asbestos/*adverse effects ; Humans ; Male ; Mesothelioma/diagnosis/drug therapy/*etiology/surgery ; Middle Aged ; Occupational Diseases/diagnosis/drug therapy/*etiology/surgery ; Peritoneal Neoplasms/diagnosis/drug therapy/*etiology/surgery ; Splenectomy ; Tomography, X-Ray Computed ; Treatment Outcome ; }, abstract = {Mesothelioma is a neoplasm originating from the mesothelial surface lining cells of the serous human cavities. It may involve the pleura, less frequently the peritoneum rarely, the pericardium, the tunica vaginalis testis and ovarian epithelium. Asbestos has been widely used in industry. A causal relationship between asbestos exposure and pleural, peritoneal and pericardial malign mesothelioma was suggested, the risk of cancer being correlated to cumulate exposure. Studies from National Cancer Institute, USA, show that the malignant mesothelioma is a rare and aggressive asbestos related malignancy. The symptomatology is insidious and poses difficult problems in diagnosis and treatment. This paper presents the case of a 59 year old patient with malignant peritoneal mesothelioma who worked almost 40 years as an electrician, exposed to asbestos fibers. He was hospitalized for important weight loss, abdominal pain and tiredness being diagnosed after imaging tests with a giant tumor, localized at the abdominal upper level, which seems to originate from the spleen's superior pole. During surgery we discovered a tumor with cystic parts, intense vascularized, which turn to be adherent in the upper side to the lower face of the left midriff cupola, to the spleen superior pole and 1/3 middle level of the great gastric curve. It was performed surgical ablation of the tumor, splenectomy with favorable postoperative evolution, the patient being now under chemotherapy treatment.}, } @article {pmid17273605, year = {2006}, author = {Capelozzi, VL and Saldiva, PH}, title = {[Histopathological diagnosis of pneumoconiosis].}, journal = {Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia}, volume = {32 Suppl 2}, number = {}, pages = {S99-112}, doi = {10.1590/s1806-37132006000800015}, pmid = {17273605}, issn = {1806-3756}, mesh = {Air Pollutants, Occupational/*adverse effects ; Asbestos/*toxicity ; Asbestosis/etiology/pathology ; Humans ; Inhalation Exposure/*adverse effects ; Lung Diseases/*etiology/pathology ; Lung Neoplasms/etiology/pathology ; Mesothelioma/etiology/pathology ; Mineral Fibers/adverse effects ; Pleural Diseases/*etiology/pathology ; }, abstract = {Asbestos-related diseases constitute a major health problem due to the great number of workers exposed to asbestos over the past 50 years. Personal injury lawsuits against industries that deal with asbestos number in the hundreds, and new cases continue to be filed. The scientific issues related to asbestos are complex, and, although the broad outlines of asbestos-related diseases have been well-established, many significant aspects (such as the pathology involved) are poorly understood. In Brazil, asbestos has been mined commercially since 1940, with production levels recently approaching 200,000 tons/year, resulting in the asbestos exposure of approximately 10,000 workers in the mining activity, and an unknown number of workers in asbestos-cement industry, primarily roofers and concrete rooftop water tank installers. One study, using appropriate methods of scientific investigation to evaluate the effects of such exposure on the health of asbestos mine workers in Brazil was conducted as part of a multicenter study and entitled "Morbidity and Mortality Among Workers Exposed to Asbestos in Mining Activities, 1940-1996". Drawing upon the experience acquired during the course of that study, the objective of the current report was to give an overview of asbestos-related diseases, with a special focus on the difficulties involved in establishing the histopathological diagnosis.}, } @article {pmid17273598, year = {2006}, author = {Terra Filho, M and de Freitas, JB and Nery, LE}, title = {[Asbestos-related diseases].}, journal = {Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia}, volume = {32 Suppl 2}, number = {}, pages = {S48-53}, doi = {10.1590/s1806-37132006000800009}, pmid = {17273598}, issn = {1806-3756}, mesh = {Asbestos/*toxicity ; Humans ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Occupational Diseases/diagnosis/*etiology ; Occupational Exposure/*adverse effects ; Pleural Diseases/etiology ; Tomography, X-Ray Computed ; Tuberculosis, Pulmonary/etiology ; }, abstract = {This chapter presents a bibliographic review of asbestos-related diseases. The latest diagnostic, radiological, computed tomography and lung function aspects of benign pleural disease, asbestosis, occupational lung cancer and mesothelioma are discussed.}, } @article {pmid17272307, year = {2007}, author = {Andujar, P and Lecomte, C and Renier, A and Fleury-Feith, J and Kheuang, L and Daubriac, J and Janin, A and Jaurand, MC}, title = {Clinico-pathological features and somatic gene alterations in refractory ceramic fibre-induced murine mesothelioma reveal mineral fibre-induced mesothelioma identities.}, journal = {Carcinogenesis}, volume = {28}, number = {7}, pages = {1599-1605}, pmid = {17272307}, issn = {0143-3334}, mesh = {Animals ; Ascites/pathology ; Cells, Cultured ; Ceramics/*toxicity ; Cyclin-Dependent Kinase Inhibitor Proteins/metabolism ; Cyclin-Dependent Kinase Inhibitor p16/metabolism ; Disease Models, Animal ; Mesothelioma/chemically induced/*metabolism/pathology ; Mice ; Mice, Knockout ; Mineral Fibers/toxicity ; Neurofibromin 2/genetics/*metabolism ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {Although human malignant mesothelioma (HMM) is mainly caused by asbestos exposure, refractory ceramic fibres (RCFs) have been classified as possibly carcinogenic to humans on the basis of their biological effects in rodents' lung and pleura and in cultured cells. Hence, further investigations are needed to clarify the mechanism of fibre-induced carcinogenicity and to prevent use of harmful particles. In a previous study, mesotheliomas were found in hemizygous Nf2 (Nf2(+/-)) mice exposed to asbestos fibres, and showed similar alterations in genes at the Ink4 locus and in Trp53 as described in HMM. Here we found that Nf2(+/-) mice developed mesotheliomas after intra-peritoneal inoculation of a RCF sample (RCF1). Clinical features in exposed mice were similar to those observed in HMM, showing association between ascite and mesothelioma. Early passages of 12 mesothelioma cell cultures from ascites developed in RCF1-exposed Nf2(+/-) mice demonstrated frequent inactivation by deletion of genes at the Ink4 locus, and low rate of Trp53 point and insertion mutations. Nf2 gene was inactivated in all cultures. In most cases, co-inactivation of genes at the Ink4 locus and Nf2 was found and, at a lower rate, of Trp53 and Nf2. These results are the first to identify mutations in RCF-induced mesothelioma. They suggest that nf2 mutation is complementary of p15(Ink4b), p16(Ink4a) and p19(Arf) or p53 mutations and show similar profile of gene alterations resulting from exposure to ceramic or asbestos fibres in Nf2(+/-) mice, also consistent with the one found in HMM. These somatic genetic changes define different pathways of mesothelial cell transformation.}, } @article {pmid17268356, year = {2006}, author = {Astoul, P}, title = {[Clinical types of thoracic cancer. Pleural mesothelioma].}, journal = {Revue des maladies respiratoires}, volume = {23}, number = {5 Pt 3}, pages = {16S177-16S187}, pmid = {17268356}, issn = {0761-8425}, mesh = {Humans ; *Mesothelioma/diagnosis/therapy ; *Pleural Neoplasms/diagnosis/therapy ; Thoracic Neoplasms/diagnosis ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare aggressive tumour, but the worldwide incidence is increasing on account of the extensive use of asbestos in the recent past. This is the principal aetiological factor and evidence of exposure should be sought in every case under investigation. Interest in this disease has increased for several reasons: the increase in incidence in the last twenty years, the heavy exposure of several groups of workers, claims for compensation for industrial disease and other medico-legal aspects, the question of environmental exposure with no threshold and the great media interest in the subject (3 million internet pages devoted to mesothelioma). Medical interest in this disease has evolved from almost total fatalism to a real interest in active management with acceptable surgery, new cytotoxic drugs and effective combinations, biological therapies, new modalities of radiotherapy and, above all, the development of multidisciplinary strategies to set up prospective randomised comparative trials which have been largely absent in this field.}, } @article {pmid17253564, year = {2007}, author = {Green, J and Dundar, Y and Dodd, S and Dickson, R and Walley, T}, title = {Pemetrexed disodium in combination with cisplatin versus other cytotoxic agents or supportive care for the treatment of malignant pleural mesothelioma.}, journal = {The Cochrane database of systematic reviews}, volume = {2007}, number = {1}, pages = {CD005574}, pmid = {17253564}, issn = {1469-493X}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Cisplatin/administration & dosage ; Glutamates/administration & dosage ; Guanine/administration & dosage/analogs & derivatives ; Humans ; Mesothelioma/*drug therapy ; Pemetrexed ; Pleural Neoplasms/*drug therapy ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a highly aggressive malignancy whose incidence is expected to increase in the United Kingdom, Western Europe, and Australia over the next 20 years as a result of occupational exposure to asbestos fibres. Surgery is feasible in only a small proportion of cases, and radiotherapy and cytotoxic chemotherapy are used in palliation. Pemetrexed is the first and only chemotherapy agent that has been granted a marketing approval for use in combination with cisplatin for the treatment of chemo-naïve patients with unresectable MPM.

OBJECTIVES: To examine evidence on the clinical effectiveness of pemetrexed disodium used in combination with cisplatin for the treatment of unresectable malignant pleural mesothelioma in chemotherapy naïve patients compared with other cytotoxic agents used alone or in combination, or supportive care.

SEARCH STRATEGY: CENTRAL (Issue 2, 2005), EMBASE (1980-2005), MEDLINE (1980-2005), HTA database (1990-2005), Web of Knowledge (1990-2005) and handsearching (including reference lists of retrieved articles and the pharmaceutical company submission to to NICE), up to October 2005.

SELECTION CRITERIA: Randomised Controlled Trials (RCTs) where the use of pemetrexed disodium in combination with cisplatin is compared with other cytotoxic agents, or supportive care for the treatment of malignant pleural mesothelioma (or non-RCTs, in the absence of RCT data).

DATA COLLECTION AND ANALYSIS: Outcomes included overall survival, tumour response, progression-free survival, toxicity and quality of life. Data extraction and quality assessment of included trials was completed independently. Trial data and quality assessment were tabulated and presented narratively.

MAIN RESULTS: One RCT involving 448 patients and comparing pemetrexed plus cisplatin versus cisplatin alone for the treatment of unresectable malignant mesothelioma was included in the review. In the intention-to-treat study population, the median survival was statistically significantly longer in the combination arm of pemetrexed plus cisplatin when compared with the cisplatin alone arm. (12.1 and 9.3 months, respectively, p=0.002). The incidence of grade 3/4 toxicities was higher in the combination arm compared with the cisplatin alone arm.

AUTHORS' CONCLUSIONS: Pemetrexed disodium in combination with cisplatin and with folic acid and vitamin B(12)supplementation may improve survival when used in combination with cisplatin in good performance status patients. Further studies including patients with poor performance status are needed in order to generalise the treatment findings. Further studies are also needed into the optimum chemotherapy, and a clear definition of what constitutes best supportive care.}, } @article {pmid17249536, year = {2007}, author = {Katsuragi, N and Shiraishi, Y and Kita, H and Toishi, M and Miyasaka, Y and Tanaka, S}, title = {[Diffuse malignant pleural mesothelioma].}, journal = {Kyobu geka. The Japanese journal of thoracic surgery}, volume = {60}, number = {1}, pages = {35-39}, pmid = {17249536}, issn = {0021-5252}, mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; *Mesothelioma/therapy ; Middle Aged ; *Pleural Neoplasms/therapy ; }, abstract = {Malignant pleural mesothelioma is an uncommon neoplasm that caused 647 deaths in Japan in 2004. The incidence of the disease is increasing and is estimated to reach its peak in 2025. We reviewed the clinical features in 11 consecutive patients with pathologically confirmed diffuse malignant pleural mesothelioma in our institution from January 1997 to December 2002. Of the 11 patients, 9 were male and 2 were female with a mean age of 66 (range, 55 to 90) years. Symptoms included dyspnea in 4 patients, chest pain in 3, dyspnea plus chest pain in 2, and cough in 2. Median period between symptom onset and presentation was 1 (range, 0 to 6) month. A history of asbestos exposure was identified in 3 patients and suspected in 5. A definitive diagnosis was made by closed pleural biopsy in 8 patients, pleural fluid cytology in 2, and autopsy in 1. Histological subtypes included epithelioid in 6 patients, sarcomatoid in 2, biphasic in 1, and unknown in 2. International Mesothelioma Interest Group (IMIG) staging included stage II in 6 patients, stage III in 3, and stage IV in 2. Median period between presentation and diagnosis was 1 (range, 0 to 22) month. Treatment included intrapleural chemotherapy in 4 patients, extrapleural pneumonectomy in 3, pleural drainage in 2, and best supportive care in 2. During the follow-up period, 9 patients died and 2 survived. Median survival time after diagnosis was 3 (range, 0 to 51) months. Of the 11 patients, 7 (64%) died within 6 months after the first presentation, and only 1 (9%) lived longer than 2 years after diagnosis.}, } @article {pmid17242414, year = {2006}, author = {Barreiro, TJ and Katzman, PJ}, title = {Malignant mesothelioma: a case presentation and review.}, journal = {The Journal of the American Osteopathic Association}, volume = {106}, number = {12}, pages = {699-704}, pmid = {17242414}, issn = {0098-6151}, mesh = {Adenocarcinoma/diagnosis/secondary ; Aged ; Biopsy ; Diagnosis, Differential ; Fatal Outcome ; Humans ; Male ; Mesothelioma/diagnostic imaging/*pathology ; Pleural Neoplasms/diagnostic imaging/*pathology ; Radiography, Thoracic ; Tomography, X-Ray Computed ; }, abstract = {Diffuse malignant mesothelioma is the most common primary tumor involving the pleura. Unfortunately, it also poses the most difficulty for physicians to diagnose and treat. Latency from the time of initial asbestos exposure, clinical features of chest pain and dyspnea, and radiographic findings of pleural effusion or pleural thickening are the characteristic features. Pathologic verification remains challenging. The primary distinctions to be made are between reactive and neoplastic mesothelial processes and between malignant mesothelioma and metastatic adenocarcinoma. Adequate tissue sampling is important to help diagnose malignant mesothelioma. This article describes a rare subtype of mesothelioma and illustrates the difficulty in establishing the diagnosis. Also included is a discussion of the clinical features, diagnostic dilemmas, and unsatisfactory outcome associated with this disease.}, } @article {pmid17240648, year = {2007}, author = {Chiappino, G}, title = {[Perseverare diabolicum: when will the real prevention of mesothelioma start?].}, journal = {La Medicina del lavoro}, volume = {98}, number = {1}, pages = {73-76}, pmid = {17240648}, issn = {0025-7818}, mesh = {Asbestos ; Asbestosis/complications/*prevention & control ; Humans ; Lung Neoplasms/etiology/*prevention & control ; Mesothelioma/etiology/*prevention & control ; Mineral Fibers ; }, } @article {pmid17240643, year = {2007}, author = {Scarselli, A and Binazzi, A and Altavista, P and Mastrantonio, M and Uccelli, R and Marinaccio, A}, title = {[Malignant pleural cancers mortality and compensated cases for asbestos related diseases in Lazio municipalities (1980-2001)].}, journal = {La Medicina del lavoro}, volume = {98}, number = {1}, pages = {30-38}, pmid = {17240643}, issn = {0025-7818}, mesh = {Asbestosis/*epidemiology ; Cluster Analysis ; Female ; Humans ; Insurance/*statistics & numerical data ; Italy/epidemiology ; Male ; Pleural Neoplasms/*mortality ; }, abstract = {BACKGROUND: Occupational exposure to asbestos has been widely reported in the Region, but a high risk for non-occupational and environmental contaminations have also been documented.

OBJECTIVES: To describe the geographical distribution ofpleural cancer deaths and compensated asbestosis cases from 1980 to 2001 in the Lazio Region.

METHODS: For each municipality Standardized Mortality Ratios (SMRs) for pleural cancer and Standardized Incidence Ratios (SIRs) for asbestosis were estimated. Expected cases were estimated from age and gender specific rates in Lazio. SatScan software was used to identify clusters and to verf;j their statistical significance.

RESULTS: 789 deaths from pleural cancer (495 males and 294 females) occurred in Lazio from 1980 to 2001. The standardized mortality rate per 100.000 inhabitants is 0,74 (0,95 for males and 0,54 for females). The main excess mortality from pleural cancer occurred in the municipalities of Civitavecchia (SMR: 269,9; 95% CI: 164,9 - 416,8), Colleferro (SMR: 304,9; 95% CI: 139,4-578,8) and Rocca Priora (SMR: 379,2; 95% CI: 103,3-970,9). Significant SIRs for compensated asbestosis cases were found in the industrial areas of the Naples-Rome highway and in the shipyard area of Civitavecchia. Nofemale compensated cases were found. The most important clusters were identified in the municipality of Civitavecchia for pleural cancer (p-value = 0,117) and in the Colleferro industrial area for compensated asbestosis cases (p-value = 0,001).

CONCLUSIONS: Epidemiological surveillance of incident cases of malignant mesothelioma in the Lazio Region and the investigation of modalities of asbestos exposure are urgently needed for prevention of occupational diseases.}, } @article {pmid17219771, year = {2006}, author = {Merler, E and Roberti, S and Bressan, V}, title = {[Systematic research and etiological diagnosis of lung tumors].}, journal = {La Medicina del lavoro}, volume = {97}, number = {6}, pages = {807-809}, pmid = {17219771}, issn = {0025-7818}, mesh = {Asbestos/*adverse effects ; Italy ; Lung Neoplasms/*diagnosis/etiology ; Mesothelioma/*diagnosis/etiology ; Occupational Exposure/*adverse effects ; Occupations ; }, } @article {pmid17219766, year = {2006}, author = {Aiani, MR and Settimi, L and Festa, R and De Stefani, M and Mensi, C}, title = {[Cluster of malignant mesothelioma cases in a thermostat manufacturing industry].}, journal = {La Medicina del lavoro}, volume = {97}, number = {6}, pages = {774-778}, pmid = {17219766}, issn = {0025-7818}, mesh = {Aged ; Asbestos/*adverse effects ; Female ; Humans ; Italy ; Mesothelioma/diagnosis/*etiology ; Middle Aged ; Occupational Exposure/*adverse effects ; Peritoneal Neoplasms/diagnosis/*etiology ; Pleural Neoplasms/diagnosis/*etiology ; *Registries ; Surveys and Questionnaires ; Time Factors ; }, abstract = {BACKGROUND: Malignant mesothelioma is a rare disease and the identification of a cluster of cases suggests a possible presence of an asbestos contamination source.

OBJECTIVES: To describe 3 cases of malignant mesothelioma (2 pleural and 1 peritoneal) that occurred in workers employed in the same thermostat factory.

METHODS: Since this occupational sector is not traditionally known for asbestos exposure the Lombardy Mesothelioma Registry proposed to Local Occupational Health Unit to investigate this industry.

RESULTS: From the first inspection of the plant, an environmental asbestos contamination (ropes covering oven handle and gasket) was found. But the greatest source of exposure was identified in the melamine resin reinforced with asbestos that constituted some internal parts of thermostats and that were sheared and perforated by the workers. So the 3 cases were defined as occupational diseases and legal procedures were initiated.

CONCLUSION: The results underline the importance of a close cooperation within Local Occupational Health Units and Mesothelioma Registry in the identification and evaluation of asbestos occupational exposure otherwise not recognized, determining thus the loss of precious information.}, } @article {pmid19662202, year = {2007}, author = {Davidson, B}, title = {Expression of cancer-associated molecules in malignant mesothelioma.}, journal = {Biomarker insights}, volume = {2}, number = {}, pages = {173-184}, pmid = {19662202}, issn = {1177-2719}, abstract = {Malignant mesothelioma (MM) is a malignant tumor derived from mesothelial cells, native cells of the body cavities. Exposure to asbestos is the most strongly established etiologic factor, predominantly for the most common disease form, pleural mesothelioma. The pathogenesis of MM involves the accumulation of extensive cytogenetic changes, as well as cancer-related phenotypic alterations that facilitate tumor cell survival, invasion and metastasis. This review presents current knowledge regarding the biological characteristics of this disease that are linked to the so-called hallmarks of cancer. In addition, data suggesting that the anatomic site (solid tumor vs. effusion) affects the expression of metastasis-associated and regulatory molecules in MM are presented. Finally, recent work in which high-throughput methodology has been applied to MM research is reviewed. The data obtained in the reviewed research may aid in defining new prognostic markers and therapeutic targets for this aggressive disease in the future.}, } @article {pmid17190247, year = {2006}, author = {Isele, H}, title = {[Asbestos and sequelae. Noli me tangere].}, journal = {MMW Fortschritte der Medizin}, volume = {148}, number = {41}, pages = {8}, doi = {10.1007/BF03364772}, pmid = {17190247}, issn = {1438-3276}, mesh = {Asbestos/*adverse effects ; Construction Materials/*adverse effects ; Cross-Sectional Studies ; Germany ; Humans ; Mesothelioma/epidemiology/*prevention & control ; Pleural Neoplasms/epidemiology/*prevention & control ; Risk Factors ; }, } @article {pmid17178853, year = {2006}, author = {Thomas, DD and Espey, MG and Pociask, DA and Ridnour, LA and Donzelli, S and Wink, DA}, title = {Asbestos redirects nitric oxide signaling through rapid catalytic conversion to nitrite.}, journal = {Cancer research}, volume = {66}, number = {24}, pages = {11600-11604}, doi = {10.1158/0008-5472.CAN-06-1140}, pmid = {17178853}, issn = {0008-5472}, mesh = {Animals ; Asbestos/*pharmacology ; Cattle ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/drug effects ; Nitric Oxide/*physiology ; Nitrites/*metabolism ; Phosphoserine ; Serum Albumin, Bovine/*drug effects ; Signal Transduction/*drug effects ; Tumor Suppressor Protein p53/drug effects ; }, abstract = {Asbestos exposure is strongly associated with the development of malignant mesothelioma, yet the mechanistic basis of this observation has not been resolved. Carcinogenic transformation or tumor progression mediated by asbestos may be related to the generation of free radical species and perturbation of cell signaling and transcription factors. We report here that exposure of human mesothelioma or lung carcinoma cells to nitric oxide (NO) in the presence of crocidolite asbestos resulted in a marked decrease in intracellular nitrosation and diminished NO-induced posttranslational modifications of tumor-associated proteins (hypoxia-inducible factor-1alpha and p53). Crocidolite rapidly scavenged NO with concomitant conversion to nitrite (NO(2)(-)). Crocidolite also catalyzed the nitration of cellular proteins in the presence of NO(2)(-) and hydrogen peroxide. Nitrated protein adducts are a prominent feature of asbestos-induced lung injury. These data highlight the ability of asbestos to induce phenotypic cellular changes through two processes: (a) by directly reducing bioactive NO levels and preventing its subsequent interaction with target molecules and (b) by increasing oxidative damage and protein modifications through NO(2) production and 3-nitrotyrosine formation.}, } @article {pmid17176944, year = {2006}, author = {Tomatis, L and Cantoni, S and Carnevale, F and Merler, E and Mollo, F and Ricci, P and Silvestri, S and Vineis, P and Terracini, B}, title = {[The role of asbestos fibre dimensions in the pathogenesis and prevention of mesothelioma].}, journal = {Epidemiologia e prevenzione}, volume = {30}, number = {4-5}, pages = {289-294}, pmid = {17176944}, issn = {1120-9763}, mesh = {Asbestos/*adverse effects ; Carcinogens ; Humans ; Italy/epidemiology ; Mesothelioma/epidemiology/*etiology/*prevention & control ; Mineral Fibers/adverse effects ; Particle Size ; Pleural Neoplasms/epidemiology/*etiology/*prevention & control ; }, abstract = {The particular point of view, recently published by Gerolamo Chiappino, on the pathogenetic role of asbestos fibres size in the origin of mesothelioma and on the possibility of mesothelioma prevention until the middle of the '80s needs to be critically clarified. The suggestion of an exclusive role of ultrashort and ultrathin fibres in the origin of mesothelioma is based on a biased interpretation of the literature. A review of the epidemiological, experimental, and molecular literature suggests that Chiappino's statements on the role of dose, dose-response effect, and genetic susceptibility are scientifically unsound Chiappino states that, in the past, in the workplaces where use and exposure to asbestos were not stopped, any reduction in the intensity of exposure by means of dust control measures or personal protective equipment would not have contributed to reduce the frequency of mesothelioma. In the authors' opinion the underlying assumptions are invalid.}, } @article {pmid17176936, year = {2006}, author = {Cernigliaro, A and Fano, V and Addario, SP and Caruso, S and Pennisi, P and Forastiere, F and Perucci, CA and Comba, P and Scondotto, S}, title = {[Mortality and hospital discharges in the population of Biancavilla (Sicily) contaminated by natural fibres].}, journal = {Epidemiologia e prevenzione}, volume = {30}, number = {4-5}, pages = {227-231}, pmid = {17176936}, issn = {1120-9763}, mesh = {Asbestos, Amphibole/*adverse effects ; Cardiovascular Diseases/mortality ; *Environmental Exposure ; Female ; Geological Phenomena ; Geology ; Hospitalization/statistics & numerical data ; Humans ; Lung Diseases/mortality ; Male ; Medical Records ; Mesothelioma/epidemiology/*etiology/*mortality ; Mineral Fibers/adverse effects ; Pleural Neoplasms/epidemiology/*etiology/*mortality ; Pulmonary Disease, Chronic Obstructive/mortality ; Sicily/epidemiology ; Survival Analysis ; }, abstract = {OBJECTIVE: The volcanic area of Biancavilla (Sicily Italy) has been included by the Italian national law among the areas of "environmental reclamation" due to the presence of amphibole fluoro-edenitic fibres in the environment. The aim of the study was to evaluate the health of residents in the area, through the analysis of the mortality registry and the hospital discharge records.

DESIGN: Age, cause and gender specific indirect standardized mortality ratios SMR (1995-2000) and morbidity ratios SHR (2001-2003) were computed with 95% confidence intervals, using the population of surrounding municipalities as reference.

RESULTS: statistically significant increases in mortality and morbidity were observed, both in men and women, for malignant pleural neoplasms (mortality: men SMR= 700, 6 observed; women SMR= 840, 3 observed; hospital admissions: women SHR= 1210, 5 observed), cardiovascular diseases (mortality: men SMR= 115, 267 observed, women SMR= 115, 278 observed; hospital admissions: men SHR= 109, 631 observed; women SHR= 114, 528 observed) and respiratory diseases (mortality: men SMR= 164, 68 observed; women: SMR= 215, 44 observed; hospital admissions: men SHR= 139, 558 observed, women SHR= 125, 374 observed).

CONCLUSIONS: the excesses observed in this study are consistent with previous findings and suggest the need for further investigations aimed at improving the knowledge of the mineralogical aspects of the fibres, the assessment of human exposure and at estimating the prevalence of pleural plaques and lung fibrosis.}, } @article {pmid17171985, year = {2006}, author = {Mensi, C and Macchione, M and Termine, L and Rivolta, G and Riboldi, L and Chiappino, G}, title = {[Information of the registry of mesothelioma in Lombardy: the asbestos risk in rotogravure].}, journal = {La Medicina del lavoro}, volume = {97}, number = {5}, pages = {726}, pmid = {17171985}, issn = {0025-7818}, mesh = {Asbestos/*adverse effects ; Humans ; Italy ; Male ; Mesothelioma/*etiology ; Occupational Exposure/*adverse effects ; *Printing ; *Registries ; Risk Factors ; }, } @article {pmid17171980, year = {2006}, author = {Pannelli, F and Montanaro, F and Pascucci, C and Mirabelli, D and Gennaro, V}, title = {[Mesothelioma incidence and time trend in the worlds].}, journal = {La Medicina del lavoro}, volume = {97}, number = {5}, pages = {682-693}, pmid = {17171980}, issn = {0025-7818}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Female ; Humans ; Incidence ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Pleural Neoplasms/*epidemiology ; *Registries ; Sex Factors ; Time Factors ; }, abstract = {BACKGROUND: Due to its adaptability to different uses, asbestos was increasingly employed in many working and domestic areas up to the 1970s-1980s, when its aetiological role in the onset of pleural mesothelioma (Mm) was recognized. Since then Mm cases have been continuously increasing and no decline is expected until 2020, despite the fact that most industrialized countries banned asbestos use a few decades ago.

OBJECTIVES: The aim of this study was to analyse Mm incidence in the World during the last ten years, also considering asbestos consumption in diferent areas.

METHODS: Incidence age-standardized rates (ASR) from Cancer Registries included in Cancer Incidence in Five Continents, Vol. VII and VIII, and, when appropriate, standardized rate ratio (SRR) with confidence interval were estimated.

RESULTS: The highest incidence rates among males were observed in Liguria and Australia. After Liguria, Maastricht and Scotland in Europe, North East Regions and Piedmont in Italy showed high rates. Among females, the highest incidence rates were observed in Liguria, among black women in New Orleans and in the province of Varese. SRRs revealed increased rates, not always significant, in almost all areas among males and in about 50% of the areas among females, although the variation was significant only in Varese.

CONCLUSIONS: These results confirmed a relationship between Mm risk and asbestos use, revealing high incidence rates in Australia (mining), Italy (shipyards, building, goods handling, heavy industries and sea trade) and Great Britain (shipyards). Mm cases increased in areas with elevated incidence rates, suggesting that larger amounts of asbestos were probably used for a longer period. Finally, no Mm cases were registered in some areas, which probably signifies a lack (or a delay) of risk referred to the investigated period.}, } @article {pmid17166401, year = {2006}, author = {Nishimura, Y and Miura, Y and Maeda, M and Hayashi, H and Dong, M and Katsuyama, H and Tomita, M and Hyodoh, F and Kusaka, M and Uesaka, A and Kuribayashi, K and Fukuoka, K and Nakano, T and Kashimoto, T and Osuki, T}, title = {Expression of the T cell receptor Vbeta repertoire in a human T cell resistant to asbestos-induced apoptosis and peripheral blood T cells from patients with silica and asbestos-related diseases.}, journal = {International journal of immunopathology and pharmacology}, volume = {19}, number = {4}, pages = {795-805}, doi = {10.1177/039463200601900409}, pmid = {17166401}, issn = {0394-6320}, mesh = {Adult ; Apoptosis/*drug effects ; Asbestos/*toxicity ; Asbestosis/*immunology ; Cell Line, Transformed ; Female ; Humans ; Male ; Receptors, Antigen, T-Cell, alpha-beta/*genetics ; Silicon Dioxide/*toxicity ; Silicosis/*immunology ; }, abstract = {To explore the effects of asbestos and silica on the human immune system, an experimental model of low-dose and long-term exposure was established using a human HTLV-1-immortalized polyclonal T cell line, MT-2 (MT-2Org). MT-2 cells were continuously exposed to asbestos at a concentration (10 microg/ml) which does not induce complete cell death during short-term exposure. After acquiring resistance to CB-induced apoptosis (designated MT-2Rst), an immunological comparison was made between the MT-2Org and MT-2Rst lines in terms of T cell receptor-Vbeta (TcR-Vbeta) expression. MT-2Rst cells showed excess expression of various TcR-Vbeta, although TcR-Vbeta-overpresenting cells were characterized as undergoing apoptosis due to first contact with CB. Patients with asbestos-related diseases (ARD), such as asbestosis and malignant mesothelioma, were compared with silicosis (SIL) patients as a disease control and with healthy donors (HD). SIL and ARD not only differed in their causative materials, silica and asbestos as mineral silicates, but also in terms of complications; autoimmune disorders in SIL and tumors in ARD. ARD patients showed a restricted overpresentation of TcR-Vbeta without clonal expansion, whereas SIL patients revealed significant overpresentation of TcR-Vbeta 7.2. These experimental and clinical analyses indicate the superantigenic and dysregulation of autoimmunity-inducing effects of asbestos and silica, respectively.}, } @article {pmid17158287, year = {2006}, author = {Kelsh, MA and Berman, DW and Langer, AM}, title = {Residential proximity to naturally occurring asbestos and mesothelioma risks: further consideration of exposure misclassification and occupational confounding.}, journal = {American journal of respiratory and critical care medicine}, volume = {174}, number = {12}, pages = {1400; author reply 1400-1}, doi = {10.1164/ajrccm.174.12.1400}, pmid = {17158287}, issn = {1073-449X}, mesh = {Asbestos/*toxicity ; *Environmental Exposure ; Humans ; Mesothelioma/*etiology ; Occupational Exposure ; Residence Characteristics ; }, } @article {pmid17154412, year = {2007}, author = {Zygielbaum, PS}, title = {Ending asbestos poisoning: global advocacy from a survivor's view.}, journal = {American journal of industrial medicine}, volume = {50}, number = {1}, pages = {68-70}, doi = {10.1002/ajim.20392}, pmid = {17154412}, issn = {0271-3586}, mesh = {Asbestos/*poisoning ; *Consumer Advocacy/legislation & jurisprudence ; Environmental Exposure/*prevention & control ; Humans ; Mesothelioma/chemically induced/prevention & control ; Politics ; Public Opinion ; United States ; }, } @article {pmid17154405, year = {2007}, author = {Kazan-Allen, L}, title = {The 2nd ADAO Asbestos Conference.}, journal = {American journal of industrial medicine}, volume = {50}, number = {1}, pages = {52-62}, doi = {10.1002/ajim.20397}, pmid = {17154405}, issn = {0271-3586}, mesh = {Asbestos/adverse effects ; Asbestosis/*prevention & control ; Environmental Exposure/prevention & control ; Humans ; International Cooperation ; Mesothelioma/*prevention & control ; Patient Advocacy ; United States ; }, abstract = {On National Asbestos Awareness Day 2006, a conference was held at Mount Sinai, the home ground of Dr. Irving J. Selikoff, who, more than any other single individual, started the debate about occupational hazards in the U.S. Four decades after the pioneering conference on the Biological Effects of Asbestos was organized by Drs. Selikoff and Churg, asbestos victims and their relatives, public health campaigners, medical professionals, journalists and community representatives convened in New York City to assess the progress that had been made in raising public, professional and political awareness of asbestos-related diseases. The report which follows conveys the substance of their presentations and highlights key issues which were discussed.}, } @article {pmid17144416, year = {2006}, author = {Piolatto, PG and Pira, E and Putzu, MG and Massiccio, M and Romano, C}, title = {[Asbestosis and microfiber role].}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {28}, number = {3}, pages = {273-275}, pmid = {17144416}, issn = {1592-7830}, mesh = {Asbestos/*adverse effects ; Asbestosis/*etiology ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Mineral Fibers/*adverse effects ; Occupational Diseases/*etiology ; Particle Size ; }, abstract = {Based on the predominant content of thin and short asbestos fibres in lung and mesothelioma tissues, it was recently stated (2005) that such fibres "appear to contribute to the causation of human malignant mesothelioma". In another study of the same year it was stated that fibres in the order of few microm length and 0.2 microm diameter are the sole able to induce mesothelioma. This scientific conclusions entail some implications from practical point of view. The enormous amount of information gained on asbestos in the last decades is based on the definition of a fibre as an alongated particle with an aspect-ratio of at least 3:1, a diameter < or = 3 microm and a length > or = 5 microm. These parameters were used up today to define occupational and in some case non-occupational limits. In which way can "reference" values be established if all lengths or only fibres shorter than 5 microm are considered? Nowadays we have no answer. Secondly, assuming a prevalent role of such fibres especially in mesothelioma cases, how can reliable estimates of past exposure obtained in a medico-legal context, since they have never been counted? Morever, how might he the employer responsibility assessed since short fibres were not measured by definition pathogenic, and this not measured, nor were there appropriate filtering systems up to the middle of the '80?}, } @article {pmid17137779, year = {2007}, author = {Scherpereel, A and , }, title = {Guidelines of the French Speaking Society for Chest Medicine for management of malignant pleural mesothelioma.}, journal = {Respiratory medicine}, volume = {101}, number = {6}, pages = {1265-1276}, doi = {10.1016/j.rmed.2006.10.018}, pmid = {17137779}, issn = {0954-6111}, mesh = {Analgesia/methods ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Asbestos/administration & dosage/adverse effects ; Environmental Exposure/analysis ; France ; Humans ; Mass Screening/methods ; Mesothelioma/diagnosis/etiology/*therapy ; Pleural Neoplasms/diagnosis/etiology/*therapy ; Prognosis ; Quality of Life ; }, abstract = {Previously considered as a rare tumor, malignant pleural mesothelioma (MPM) has become a very important public health issue. In fact, MPM is a tumor with a poor survival, and its incidence is expected to continue to increase for at least the next 10 years. Asbestos exposure is the main factor involved in MPM pathogenesis. The diagnosis of MPM may be difficult because of differential diagnosis such as pleural benign disease induced by asbestos exposure or pleural metastasis of adenocarcinoma. Management of patients with MPM also remains complicated because they are often referred for evaluation late in the evolution of the disease. Moreover, MPM exhibits a high resistance to radiotherapy and chemotherapy; only few patients are candidates for radical surgery. New therapeutic strategies such as gene or cell therapy are still on clinical trial. Therefore, an optimal treatment of MPM is not clearly defined yet, despite the introduction of recent drugs. Between April 2005 and January 2006, the French Speaking Society for Chest Medicine (SPLF), in collaboration with other French scientific societies, brought together experts on mesothelioma to draw up recommendations in order to provide clinicians with clear, concise, up-to-date guidelines on management of MPM, presented in this report.}, } @article {pmid17130182, year = {2007}, author = {Yan, TD and Welch, L and Black, D and Sugarbaker, PH}, title = {A systematic review on the efficacy of cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for diffuse malignancy peritoneal mesothelioma.}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {18}, number = {5}, pages = {827-834}, doi = {10.1093/annonc/mdl428}, pmid = {17130182}, issn = {0923-7534}, mesh = {Antibiotics, Antineoplastic/administration & dosage ; Antineoplastic Agents, Phytogenic/administration & dosage ; Asbestos/toxicity ; Cisplatin/administration & dosage ; Combined Modality Therapy ; Doxorubicin/administration & dosage ; Follow-Up Studies ; Humans ; Infusions, Parenteral ; Mesothelioma/chemically induced/*drug therapy/*surgery ; Peritoneal Neoplasms/chemically induced/*drug therapy/*surgery ; Survival Analysis ; Time Factors ; Treatment Outcome ; }, abstract = {BACKGROUND: In the past, diffuse malignant peritoneal mesothelioma (DMPM) was regarded as a preterminal condition. The length of survival was dependent upon the aggressive versus indolent biologic behavior of the neoplasm. The overall median survival was approximately 1 year after systemic chemotherapy. Cytoreductive surgery (CRS) combined with perioperative intraperitoneal chemotherapy (PIC) has been used as a treatment alternative, but the efficacy of this combined treatment remains to be established.

PATIENTS AND METHODS: Searches for relevant studies published in peer-reviewed medical journals on CRS and PIC for DMPM before May 2006 were carried out on six databases. The reference lists of all retrieved articles were reviewed for further identification of potentially relevant studies. Expert academic surgeons in Washington, DC, USA were asked whether they knew about any important unpublished data. Two investigators independently evaluated each study according to predefined criteria. The quality of each study was assessed. Clinical effectiveness was synthesized through a narrative review with full tabulation of results of all included studies.

RESULTS: Seven prospective observational studies from six tertiary institutions were available, allowing 240 DMPM patients for assessment. The median survival ranged from 34-92 months. The 1-, 3- and 5-year survival varied from 60% to 88%, 43% to 65% and 29% to 59%, respectively. The perioperative morbidity varied from 25% to 40% and mortality ranged from 0% to 8%.

CONCLUSIONS: This systematic review evaluated the current evidence for CRS and PIC for DMPM. Seven observational studies were available for assessment, which demonstrated an improved overall survival, as compared to historical controls, using systemic chemotherapy and palliative surgery.}, } @article {pmid17119263, year = {2006}, author = {Watterson, A and Gorman, T and Malcolm, C and Robinson, M and Beck, M}, title = {The economic costs of health service treatments for asbestos-related mesothelioma deaths.}, journal = {Annals of the New York Academy of Sciences}, volume = {1076}, number = {}, pages = {871-881}, doi = {10.1196/annals.1371.042}, pmid = {17119263}, issn = {0077-8923}, mesh = {Asbestos/*toxicity ; Female ; *Hospital Costs ; Humans ; Male ; Mesothelioma/economics/*therapy ; State Medicine ; United Kingdom ; }, abstract = {This article explores the complex and neglected picture of occupational and environmental disease healthcare costs specifically relating to asbestos. Diagnosed mesothelioma cases in Scotland in one calendar year were used to investigate the subject in greater depth. Data from UK sources on asbestos disease types recorded in 2000 and their disease treatment costs were obtained. Acute care economic costs of these diseases are estimated. One hundred and twenty diagnosed, recorded, and treated cases of asbestos-related diseases occurred in 2000 in Scotland. Mesothelioma accounted for 100 cases and directly cost Scottish National Health Service hospitals an estimated 942,038 pounds. The estimated UK figure in 2000 was at least 16,014,646 pounds because official figures for diagnosed and recorded deaths from mesothelioma are running at over 1700 a year with rises predicted for 2010 of 2000 deaths. By 2003, 50,000 people in the UK had died from diagnosed and recorded mesothelioma since records began. Earlier disease treatment costs would have been significantly lower than those in 2000 but, at 2000 prices, cost to the UK was roughly 471,019,000 pounds in acute hospital expenditure. Figures for primary care costs, including caregiver costs, are incomplete or unknown. These disease costs are substantial and have some international generalizability. Treatment patterns and costs vary greatly. Many lung cancer cases due to asbestos exposure occur globally for each mesothelioma case. Hence figures provided in this article are certain to be gross underestimates of the total health service and personal economic costs of asbestos illness and treatment in Scotland.}, } @article {pmid17119254, year = {2006}, author = {Bruno, C and Comba, P and Zona, A}, title = {Adverse health effects of fluoro-edenitic fibers: epidemiological evidence and public health priorities.}, journal = {Annals of the New York Academy of Sciences}, volume = {1076}, number = {}, pages = {778-783}, doi = {10.1196/annals.1371.020}, pmid = {17119254}, issn = {0077-8923}, mesh = {Asbestos/*toxicity ; Environmental Exposure ; Environmental Monitoring ; Environmental Pollutants/*toxicity ; Epidemiological Monitoring ; Female ; *Health Priorities ; Humans ; Italy ; Male ; Mesothelioma/chemically induced/*epidemiology ; *Public Health ; Pulmonary Disease, Chronic Obstructive/chemically induced/*epidemiology ; }, abstract = {Subsequent to the detection of a cluster of mesothelioma cases in the Sicilian town of Biancavilla, located at the slopes of Etna volcano, ad hoc epidemiological studies and environmental monitoring suggested an etiological role of an asbestiform fiber present in a stone quarry. The fiber was shown to constitute a new mineral species named fluoro-edenite. Fluoro-edenitic fibers were found in the materials extracted from the quarry and used in the local building industry, as well as in soils. Besides the risk of mesothelioma, residents in Biancavilla showed a significantly increased mortality from chronic obstructive pulmonary disease, which was particularly evident among women. In the light of these findings, Biancavilla was defined a site of national interest for environmental reclamation. The first preventive action involved termination of quarrying activity, covering with asphalt of roads previously paved with local soil materials, and removal of sources of dust in the urban area. Concurrent to the implementation of environmental cleanup, some specific "second generation" studies are now being designed and performed, namely morbidity surveys based on hospital discharge cards, monitoring of fibers in sputum and health surveillance in selected population groups. In this frame, special emphasis is given to the issue of communication, both to the general public and to target groups like family doctors, teachers, and media professionals. This experience could represent a useful basis for the elaboration of a strategy to approach similar environmental issues.}, } @article {pmid17119221, year = {2006}, author = {Järvholm, B}, title = {Carcinogens in the construction industry.}, journal = {Annals of the New York Academy of Sciences}, volume = {1076}, number = {}, pages = {421-428}, doi = {10.1196/annals.1371.055}, pmid = {17119221}, issn = {0077-8923}, mesh = {Asbestos/*toxicity ; Carcinogens/*toxicity ; Humans ; *Industry ; Lung Neoplasms/*chemically induced ; Mesothelioma/*chemically induced ; *Occupational Exposure ; }, abstract = {The construction industry is a complex work environment. The work sites are temporary and rapidly changing. Asbestos has been widely used in construction industry, but the risks were primarily detected in specialized trades, such as insulation workers and plumbers. Today, the majority of cases related to asbestos exposure will occur in other occupational groups in the construction industry. In a large cohort of Swedish construction workers, insulators and plumbers constituted 37% of all cases of pleural mesothelioma between 1975 and 1984 while they constituted 21% of the cases between 1998 and 2002. It is estimated that 25-40% of all male cases of pleural mesothelioma in Sweden are caused by asbestos exposure in the construction trades. There are many other known carcinogens occurring in the construction industry, including PAHs, diesel exhausts, silica, asphalt fumes, solvents, etc., but it is difficult to estimate exposures and thus the size of the risk. The risk of cancer is less easy to detect with traditional epidemiological methods in the construction industry than in other industrial sectors. It is not sufficient to rely upon broad epidemiological data to estimate the risk of cancer due chemicals in the construction industry. Thus, a strategy to decrease exposure, e.g., to dust, seems a feasible way to reduce the risk.}, } @article {pmid17119210, year = {2006}, author = {Joshi, TK and Bhuva, UB and Katoch, P}, title = {Asbestos ban in India: challenges ahead.}, journal = {Annals of the New York Academy of Sciences}, volume = {1076}, number = {}, pages = {292-308}, doi = {10.1196/annals.1371.072}, pmid = {17119210}, issn = {0077-8923}, mesh = {Asbestos/*toxicity ; Humans ; India ; Occupational Exposure ; }, abstract = {Rapidly industrializing India is described by the International Monetary Fund as a young, disciplined, and vibrant economy with a projected growth of 6.7% for 2005. The total workforce of 397 million has only 7% of workers employed in the organized sector with construction, where asbestos exposure is prevalent, employing 4.4%. The domestic production of asbestos declined from 20,111 tons in 1998-1999 to 14,340 tons in 2002-2003. The imports from Russia and Canada increased from 61,474 tons in 1997-1998 to 97,884 tons in 2001-2002. The production of asbestos cement products went up from 0.68 million tons in 1993-1994 to 1.38 million tons in 2002-2003. The asbestos industry has been delicensed since March 2003. The number of asbestos-based units stood at 32, with the western state of Maharashtra having the largest number. According to official figures, the industry employs 8000 workers. The occupational exposure standard is still 2 fibers/mL, worse still, mesothelioma is not recognized as an occupational disease. The latest cancer registry data have no information on mesothelioma. The health and safety legislation does not cover 93% of workers in the unorganized sector where asbestos exposures are extremely high. Workers remain uninformed and untrained in dealing with asbestos exposure. Enforcement agencies are not fully conscious of the risks of asbestos exposure. Industrial hygiene assessment is seldom carried out and pathologists do not receive training in identifying mesothelioma histopathologically. The lack of political will and powerful influence of the asbestos industry are pushing India toward a disaster of unimaginable proportion.}, } @article {pmid17119209, year = {2006}, author = {Dodson, RF and Atkinson, MA}, title = {Measurements of asbestos burden in tissues.}, journal = {Annals of the New York Academy of Sciences}, volume = {1076}, number = {}, pages = {281-291}, doi = {10.1196/annals.1371.015}, pmid = {17119209}, issn = {0077-8923}, mesh = {Asbestos/*pharmacokinetics ; *Body Burden ; Humans ; Inhalation Exposure ; Microscopy, Electron ; }, abstract = {Asbestos inhaled into the lung is recognized as a potential causal agent for the development of diseases in man. The diseases induced by asbestos include lung cancer, fibrosis of the lung (asbestosis), and extrapulmonary tumors including mesothelioma (a tumor of the serosal membrane), as well as fibrosis and other changes in the pleura linings. The cause of these diseases can often be more specifically linked to asbestos exposure once tissue burden of asbestos is established. The asbestos burden in tissue can be defined as the number of asbestos bodies and/or the numbers and types of asbestos fibers found in the tissue. In either of these cases the quality of information is directly dependent on the preparative techniques and instrumentation used in the analysis. The present article will discuss the significance of findings of tissue burden based on both these variables.}, } @article {pmid17108115, year = {2006}, author = {Robinson, C and van Bruggen, I and Segal, A and Dunham, M and Sherwood, A and Koentgen, F and Robinson, BW and Lake, RA}, title = {A novel SV40 TAg transgenic model of asbestos-induced mesothelioma: malignant transformation is dose dependent.}, journal = {Cancer research}, volume = {66}, number = {22}, pages = {10786-10794}, doi = {10.1158/0008-5472.CAN-05-4668}, pmid = {17108115}, issn = {0008-5472}, mesh = {Animals ; Antigens, Polyomavirus Transforming/*genetics ; Asbestos/*poisoning ; Cell Line, Transformed ; *Cell Transformation, Neoplastic ; Dose-Response Relationship, Drug ; Mesothelin ; Mesothelioma/*etiology/genetics ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; }, abstract = {Although it has been clear for >40 years that mesothelioma can be caused by asbestos, not all patients with this disease have a history of asbestos exposure. Other factors, including non-asbestos fibers and ionizing radiation, are known to cause malignant transformation of mesothelial cells. In addition, it is likely that genetics will play some role in susceptibility. Recently, it has been suggested that SV40 viral oncogenes could contribute to the carcinogenicity of asbestos. To better understand the role of SV40, we used the mesothelin promoter to construct MexTAg mice that express SV40 large T antigen (TAg) in the mesothelial compartment. We generated four MexTAg lines that carry high, intermediate, and low copy numbers of the transgene. All of these mice show a relatively low level of spontaneous tumor development. High-copy, 299h mice rapidly developed mesotheliomas when exposed to asbestos, and these tumors were faster growing and more invasive than those developing in wild-type and single-copy (266s) mice. In addition, we found a direct relationship between transgene copy number and survival after exposure to asbestos. A single copy of TAg was sufficient to immortalize mesothelial cells in vitro, but these cells did not show evidence of malignant transformation. In contrast, cell lines developed from mesothelial cells of animals carrying multiple copies of TAg were growth factor independent and could be cloned at limiting dilution in soft agar. These data provide the first in vivo demonstration of co-carcinogenicity between SV40 and asbestos.}, } @article {pmid17090323, year = {2006}, author = {Leithner, K and Leithner, A and Clar, H and Weinhaeusel, A and Radl, R and Krippl, P and Rehak, P and Windhager, R and Haas, OA and Olschewski, H}, title = {Mesothelioma mortality in Europe: impact of asbestos consumption and simian virus 40.}, journal = {Orphanet journal of rare diseases}, volume = {1}, number = {}, pages = {44}, pmid = {17090323}, issn = {1750-1172}, mesh = {Asbestosis/*mortality ; Causality ; Comorbidity ; Drug Contamination/statistics & numerical data ; Environmental Exposure/statistics & numerical data ; Europe/epidemiology ; Female ; Humans ; Male ; Mesothelioma/*mortality/virology ; Pleural Neoplasms/*mortality/virology ; Poliovirus Vaccines ; Polyomavirus Infections/*mortality ; Sex Distribution ; *Simian virus 40 ; Survival Analysis ; Survival Rate ; Tumor Virus Infections/*mortality ; }, abstract = {BACKGROUND: It is well established that asbestos is the most important cause of mesothelioma. The role of simian virus 40 (SV40) in mesothelioma development, on the other hand, remains controversial. This potential human oncogene has been introduced into various populations through contaminated polio vaccines. The aim of this study was to investigate whether the possible presence of SV40 in various European countries, as indicated either by molecular genetic evidence or previous exposure to SV40-contaminated vaccines, had any effect on pleural cancer rates in the respective countries.

METHODS: We conducted a Medline search that covered the period from January 1969 to August 2005 for reports on the detection of SV40 DNA in human tissue samples. In addition, we collected all available information about the types of polio vaccines that had been used in these European countries and their SV40 contamination status.

RESULTS: Our ecological analysis confirms that pleural cancer mortality in males, but not in females, correlates with the extent of asbestos exposure 25 - 30 years earlier. In contrast, neither the presence of SV40 DNA in tumor samples nor a previous vaccination exposure had any detectable influence on the cancer mortality rate in neither in males (asbestos-corrected rates) nor in females.

CONCLUSION: Using the currently existing data on SV40 prevalence, no association between SV40 prevalence and asbestos-corrected male pleural cancer can be demonstrated.}, } @article {pmid17088053, year = {2007}, author = {Fletcher, SV and Clark, RJ}, title = {The Portsmouth thoracoscopy experience, an evaluation of service by retrospective case note analysis.}, journal = {Respiratory medicine}, volume = {101}, number = {5}, pages = {1021-1025}, doi = {10.1016/j.rmed.2006.08.026}, pmid = {17088053}, issn = {0954-6111}, mesh = {Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Diagnosis, Differential ; Female ; Humans ; Male ; Mesothelioma/*diagnosis/etiology ; Middle Aged ; Occupational Diseases/diagnosis/etiology ; Pleural Diseases/diagnosis ; Pleural Effusion/etiology ; Pleural Effusion, Malignant/diagnosis/etiology ; Pleural Neoplasms/*diagnosis/etiology ; Retrospective Studies ; Thoracoscopy/adverse effects/*methods ; }, abstract = {Occupational asbestos exposure has been endemic in Portsmouth. A retrospective case note analysis of 50 patients who underwent thoracoscopy over a 2-year period from January 2003 was undertaken. Biopsies were taken in 47 cases, 31 of which showed malignant mesothelioma. Thirty seven percent of those without a history of direct exposure to asbestos had mesothelioma, implying that even in the absence of an exposure history a low threshold for investigation should be adopted for the local population. There was no mortality or significant morbidity associated with the procedure. Medical thoracoscopy is safe and effective in the diagnosis of benign and malignant pleural disease particularly in this high risk population.}, } @article {pmid17078889, year = {2006}, author = {Drain, AJ and Saeb-Parsy, K and Shah, AK and Rassl, D and Ritchie, AJ}, title = {Mesothelioma with non-pleural malignancy: a red herring or just an uncommon pairing?.}, journal = {Journal of cardiothoracic surgery}, volume = {1}, number = {}, pages = {39}, pmid = {17078889}, issn = {1749-8090}, mesh = {Adult ; Aged ; Female ; Humans ; *Mesothelioma/pathology ; Middle Aged ; *Pleural Neoplasms/pathology ; }, abstract = {Malignant pleural mesothelioma (MPM) is a highly aggressive cancer of the pleura with a well-established male predominance and causative link with asbestos exposure. We report four cases of female patients with MPM referred for palliation of symptoms thought to be due to previous non-pleural malignancy.With emerging novel treatments for MPM, this article discusses four unusual cases of MPM occurring in the setting of other malignancy, highlights the importance of considering a primary diagnosis of MPM even in patients with other malignancy, and reinforces the benefits of video-assisted surgical biopsy which allows simultaneous diagnosis and treatment.}, } @article {pmid17078518, year = {2006}, author = {Manaouil, C and Graser, M and Jardé, O}, title = {Compensation of asbestos victims in France.}, journal = {Medicine and law}, volume = {25}, number = {3}, pages = {435-443}, pmid = {17078518}, issn = {0723-1393}, mesh = {Asbestos/*adverse effects ; Asbestosis/economics ; Compensation and Redress/*legislation & jurisprudence ; France ; Humans ; Mesothelioma/economics ; Pleural Neoplasms/economics ; }, abstract = {The alarming development of pathologies linked to asbestos led to the creation in France of two funds to indemnify the victims of asbestos-related illnesses: the FCAATA (Fund for asbestos workers who take early retirement), which compensates for their reduced life expectancy, and the FIVA (Indemnification fund for asbestos victims) which ensures full compensation for harm suffered by asbestos victims.}, } @article {pmid17078302, year = {2006}, author = {Pylev, LN and Vasil'eva, LA and Stadnikova, NM and Smirnova, OV and Zubakova, LE and Vezentsev, AI and Gudkova, EA and Bakhtin, AI}, title = {[Characterization of the biological properties of acid-treated chrysotile-asbestos fibers].}, journal = {Gigiena i sanitariia}, volume = {}, number = {4}, pages = {70-73}, pmid = {17078302}, issn = {0016-9900}, mesh = {Acids/*administration & dosage/*pharmacology ; Animals ; Asbestos/*chemistry/*metabolism ; Asbestos, Serpentine/*chemistry/*metabolism ; Mesothelioma/etiology/pathology ; Mutagenesis ; Pleural Neoplasms/etiology/pathology ; Rats ; }, abstract = {Boiling of chrysotile of the textile brand PRZh1-50 in concentrated hydrochloric acid for 10, 15, and 20 minutes gave rise to three chrysotile-asbestos samples. The content of MgO decreased from to 24, 19, and 9%, respectively. As compared with the baseline values, the number and force of positively charged electrical centers were less in the samples containing 24 and 19% MgO and more in the sample having 9% MgO; the negatively charged centers were present in the former two samples and absent in the third one. When the samples were intrapleurally administered to rats, their hemolytic activity, induction of active oxygen radicals, mutagenic activity (micronuclear test using murine bone marrow cells), and the frequency of mesotheliomas were less in the treated samples than in the baseline ones; but there were no differences between the treated samples. Thus, the altered physicochemical properties of the fibrillar surface of asbestos diminished its biological aggressiveness; however, increased treatment rates failed to lead to its further decrease. There was no relationship of the biological properties to the number and force of electric charges of the surface.}, } @article {pmid17069224, year = {2005}, author = {Raşcu, A and Drăghici, B and Naghi, E}, title = {[Questions and answers about asbestos].}, journal = {Pneumologia (Bucharest, Romania)}, volume = {54}, number = {4}, pages = {195-199}, pmid = {17069224}, issn = {2067-2993}, mesh = {Asbestos/*adverse effects ; Asbestosis/*etiology ; Carcinoma, Bronchogenic/etiology ; Humans ; Lung Diseases, Obstructive/etiology ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Occupational Diseases/*etiology ; Pleural Neoplasms/etiology ; Respiratory Tract Neoplasms/etiology ; }, } @article {pmid17067119, year = {2006}, author = {}, title = {Can pemetrexed help in malignant mesothelioma?.}, journal = {Drug and therapeutics bulletin}, volume = {44}, number = {10}, pages = {77-80}, doi = {10.1136/dtb.2006.441077}, pmid = {17067119}, issn = {0012-6543}, mesh = {Antineoplastic Agents/*therapeutic use ; Combined Modality Therapy ; Drug Costs ; Glutamates/*therapeutic use ; Guanine/*analogs & derivatives/therapeutic use ; Humans ; Mesothelioma/*drug therapy/radiotherapy/surgery ; Pemetrexed ; Pleural Neoplasms/*drug therapy/radiotherapy/surgery ; Quality of Life ; Randomized Controlled Trials as Topic ; Treatment Outcome ; }, abstract = {Mesothelioma is a cancer that originates in the pleura or, more rarely, the peritoneum, and is almost always due to exposure to asbestos fibres. It is typically fatal, with a median survival of about 8-14 months after diagnosis. Conventional treatment options have not improved this poor outlook. Also, the number of deaths attributable to malignant mesothelioma has been rising rapidly in the UK since the late 1960s, and is set to peak at about 1,950-2,450 per year between 2011 and 2015. It is against this background that pemetrexed (pronounced pe-me-treks-ed) (Alimta - Lilly) has recently become available for use with cisplatin for the treatment of patients with unresectable malignant pleural mesothelioma who have not previously been treated with chemotherapy. Currently, this is the only chemotherapy regimen licensed for patients with malignant pleural mesothelioma in the UK. Here we review the care of patients with malignant pleural mesothelioma, focusing on what, if anything, pemetrexed might offer such individuals.}, } @article {pmid17063831, year = {2006}, author = {Omura, Y}, title = {Asbestos as a possible major cause of malignant lung tumors (including small cell carcinoma, adenocarcinoma & mesothelioma), brain tumors (i.e. astrocytoma & glioblastoma multiforme), many other malignant tumors, intractable pain including fibromyalgia, & some cardio-vascular pathology: Safe & effective methods of reducing asbestos from normal & pathological areas.}, journal = {Acupuncture & electro-therapeutics research}, volume = {31}, number = {1-2}, pages = {61-125}, doi = {10.3727/036012906815844300}, pmid = {17063831}, issn = {0360-1293}, mesh = {Adult ; Aged ; Asbestos/adverse effects/*toxicity ; Cardiovascular Diseases/*chemically induced/*pathology ; Female ; Fibromyalgia/*chemically induced/pathology ; Humans ; Inhalation Exposure/adverse effects ; Lung Neoplasms/chemically induced/genetics/metabolism/pathology ; Male ; Microscopy, Electron, Transmission ; Middle Aged ; Neoplasms/*chemically induced/genetics/metabolism/*pathology ; Occupational Exposure/adverse effects ; Pain, Intractable/*chemically induced ; }, abstract = {High incidences of Small Cell Carcinoma & Adenocarcinoma of the lung, Astrocytoma & Glioblastoma Multiforme of the brain and Mesothelioma of the lung were found in those who had a high accumulation of Asbestos in the eyes and upper respiratory system (nose, larynx, trachea, etc.). When measured non-invasively using the Bi-Digital O-Ring Test (BDORT), brain tumors had the highest concentration of Asbestos (0.2 approximately 2.1 mg BDORT units). Relatively high levels of Asbestos (0.2 approximately 0.6 mg BDORT units) were found in: Squamous Cell Carcinoma of the lungs & esophagus, Adenocarcinoma of the larynx & breast, myelogenic leukemia, arteries of these cancers, left ventricle of failing heart, myocardial infarction, some of the narrowed arteries, varicose veins, cataracts, balding heads, hot flashes, Alzheimer's Disease and Autism. A small, round or ellipsoidal area, with diameter of 5 mm or less, was found near the center of every cancer tissue with a higher level of Asbestos (1 approximately 3 mg), As, Zn, Cr and Se, than in the rest of the tumor; this small area may be where the cancer initiated. Among areas of intractable pain with frequent recurrence and gradual worsening, about 0.2 approximately 0.5 mg BDORT units (or higher) of Asbestos were found. The author found that in the Astrocytoma and many other cancer patients, the optimal dose of DHEA produced very significant reductions of cancer cell telomere from over 1400 ng in the brain tumors (and over 900 ng in other cancers) to close to or less than 1 yg (=10(-24) g), with circulatory improvement by reduction of TXB2. Unlike the standard, widely used treatment with DHEA 25 approximately 50 mg daily, which is an overdose; we only gave one optimal dose (1.5 approximately 12.5 mg) and the beneficial effects usually lasted anywhere between 3-6 months, unless inhibiting factors were introduced. In addition, once one optimal dose of DHEA was given, the amount of Asbestos from these tumors decreased very significantly (30 approximately 99% reduction) with marked increase in urine Asbestos. One optimal dose of special Cilantro tablet reduced more Asbestos than DHEA or (+) Qi Gong Energy Stored Paper. In addition, the application of (+) Solar Energy Stored Paper often reduces 70 approximately 99% of the Asbestos, while (+) Qi Gong Energy Stored Paper reduces 50 approximately 99% of the Asbestos.}, } @article {pmid17059852, year = {2006}, author = {Stahel, RA}, title = {Malignant pleural mesothelioma: a new standard of care.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {54 Suppl 2}, number = {}, pages = {S9-S14}, doi = {10.1016/j.lungcan.2006.09.011}, pmid = {17059852}, issn = {0169-5002}, mesh = {Antineoplastic Agents/*therapeutic use ; Humans ; Mesothelioma/*therapy ; Pleural Neoplasms/*therapy ; *Pneumonectomy ; Treatment Outcome ; }, abstract = {Malignant pleural mesothelioma (MPM) is an asbestos-associated cancer that occurs most commonly in the pleural cavities and generally has a poor prognosis. A rise in the incidence of this fatal disease, which, in the past has been considered to be relatively refractory to therapy, is predicted over the next decade. The realisation that patients can benefit from systemic chemotherapy and more aggressive multimodal approaches, including extrapleural pneumonectomy (EPP), in earlier stages of disease now provides the opportunity to offer more effective treatment for this disease.}, } @article {pmid17059185, year = {2006}, author = {Tümmers, T and Bourgeois, G}, title = {["Unfortunately we will see this more often". Pleural mesothelioma].}, journal = {MMW Fortschritte der Medizin}, volume = {148}, number = {39}, pages = {5}, pmid = {17059185}, issn = {1438-3276}, mesh = {Aged, 80 and over ; Asbestos/*adverse effects ; Cross-Sectional Studies ; Germany ; Humans ; Male ; Mesothelioma/*diagnosis/epidemiology ; Pleural Neoplasms/*diagnosis/epidemiology ; Risk Factors ; Soft Tissue Neoplasms/*diagnosis/epidemiology ; }, } @article {pmid17049671, year = {2006}, author = {Edwards, JG and Swinson, DE and Jones, JL and Waller, DA and O'Byrne, KJ}, title = {EGFR expression: associations with outcome and clinicopathological variables in malignant pleural mesothelioma.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {54}, number = {3}, pages = {399-407}, doi = {10.1016/j.lungcan.2006.08.012}, pmid = {17049671}, issn = {0169-5002}, mesh = {Biomarkers, Tumor/*analysis ; Cyclooxygenase 2/analysis ; ErbB Receptors/*analysis ; Female ; Humans ; Immunohistochemistry ; Male ; Membrane Proteins/analysis ; Mesothelioma/blood supply/*mortality/pathology ; Multivariate Analysis ; Neovascularization, Pathologic/pathology ; Pleural Neoplasms/blood supply/*mortality/pathology ; Prognosis ; Proportional Hazards Models ; Survival Analysis ; Survival Rate ; }, abstract = {Malignant mesothelioma (MM) is a fatal tumour of increasing incidence which is related to asbestos exposure. This work evaluated expression in MM of Epidermal Growth Factor Receptor (EGFR) by immunohistochemistry in 168 tumour sections and its correlations with clinicopathological and biological factors. The microvessel density (MVD) was derived from CD34 immunostained sections. Hematoxylin and eosin stained sections were examined for intratumoural necrosis. COX-2 protein expression was evaluated with semi-quantitative Western blotting of homogenised tumour supernatants (n=45). EGFR expression was correlated with survival by Kaplan-Meier and log rank analysis. Univariate and multivariate Cox proportional hazards models were used to compare the effects of EGFR with clinicopathological and biological prognostic factors and prognostic scoring systems. EGFR expression was identified in 74 cases (44%) and correlated with epithelioid cell type (p<0.0001), good performance status (p<0.0001), the absence of chest pain (p<0.0001) and the presence of TN (p=0.004), but not MVD or COX-2. EGFR expression was a good prognostic factor in univariate analysis (p=0.01). Independent indicators of poor prognosis in multivariate analysis were non-epithelioid cell type (p=0.0001), weight loss, performance status and WBC>8.3x10(9)L(-1). EGFR status was not an independent prognostic factor. EGFR expression in MM correlates with epithelioid histology and TN. EGFR may be a target for selective therapies in MM.}, } @article {pmid17047960, year = {2007}, author = {Das, M and Mühlenbruch, G and Mahnken, AH and Hering, KG and Sirbu, H and Zschiesche, W and Knoll, L and Felten, MK and Kraus, T and Günther, RW and Wildberger, JE}, title = {Asbestos Surveillance Program Aachen (ASPA): initial results from baseline screening for lung cancer in asbestos-exposed high-risk individuals using low-dose multidetector-row CT.}, journal = {European radiology}, volume = {17}, number = {5}, pages = {1193-1199}, pmid = {17047960}, issn = {0938-7994}, mesh = {Aged ; Asbestosis/*diagnostic imaging/epidemiology ; Germany/epidemiology ; Humans ; Lung Neoplasms/*diagnostic imaging/epidemiology ; Male ; Mesothelioma/*diagnostic imaging/epidemiology ; Occupational Exposure/*adverse effects ; Population Surveillance ; Power Plants ; Prevalence ; Prospective Studies ; Radiographic Image Interpretation, Computer-Assisted ; Risk Assessment ; Risk Factors ; Software ; Time Factors ; Tomography, X-Ray Computed/*methods ; }, abstract = {The purpose of this study was to assess the prevalence of lung cancer in a high-risk asbestos-exposed cohort using low-dose MDCT. Of a population of 5,389 former power-plant workers, 316 were characterized as individuals at highest risk for lung cancer according to a lung-cancer risk model including age, asbestos exposure and smoking habits. Of these 316, 187 (mean age: 66.6 years) individuals were included in a prospective trial. Mean asbestos exposure time was 29.65 years and 89% were smokers. Screening was performed on a 16-slice MDCT (Siemens) with low-dose technique (10/20 mAs(eff.); 1 mm/0.5 mm increment). In addition to soft copy PACS reading analysis on a workstation with a dedicated lung analysis software (LungCARE; Siemens) was performed. One strongly suspicious mass and eight cases of histologically proven lung cancer were found plus 491 additional pulmonary nodules (average volume: 40.72 ml, average diameter 4.62 mm). Asbestos-related changes (pleural plaques, fibrosis) were visible in 80 individuals. Lung cancer screening in this high-risk cohort showed a prevalence of lung cancer of 4.28% (8/187) at baseline screening with an additional large number of indeterminate pulmonary nodules. Low-dose MDCT proved to be feasible in this highly selected population.}, } @article {pmid17044196, year = {2006}, author = {Carbone, M and Bedrossian, CW}, title = {The pathogenesis of mesothelioma.}, journal = {Seminars in diagnostic pathology}, volume = {23}, number = {1}, pages = {56-60}, doi = {10.1053/j.semdp.2006.08.002}, pmid = {17044196}, issn = {0740-2570}, mesh = {Animals ; Asbestos/*adverse effects ; *Carcinogens ; Genetic Predisposition to Disease ; Humans ; Mesothelioma/*chemically induced/genetics ; Pleural Neoplasms/*chemically induced/genetics ; }, abstract = {Widespread asbestos exposure during the past century has been linked to the dramatic increased incidence of malignant mesothelioma (MM), a malignancy that was so rare until 1950-1960 that some pathologists questioned its existence. Although asbestos has been clearly linked to MM pathogenesis, until recently the mechanisms of asbestos carcinogenesis in humans have remained obscure. Recent results revealed that asbestos carcinogenesis in humans and in rodents is linked to the activation of the AP-1 pathway, which induces cell division, and to the secretion of TNF-alpha (and the expression of its receptor) by mesothelial cells and by nearby macrophages exposed to asbestos. In mesothelial cells, TNF-alpha signaling through NF-kappaB activation prevents apoptosis and cell death, allowing mesothelial cells to survive the genetic damage induced by asbestos and divide. In addition, mutagenic oxygen radicals released mainly by lung macrophages may contribute to asbestos carcinogenesis. Very recent results indicate that mineral fiber carcinogenesis can be influenced by genetics and microbial infections. Genetic susceptibility to the mineral fiber erionite has been demonstrated in some Turkish families and causes a MM epidemic in Cappadocia, Turkey. In these mesothelioma families, exposure to minimal amounts of erionite or asbestos appears sufficient to cause mesothelioma. Recent results (Kroczynska B, et al: Proc Natl Acad Sci USA, in press), demonstrate that SV40 and crocidolite asbestos are cocarcinogens and that, in the presence of SV40, significantly lower amounts of asbestos suffice to induce MM. These findings indicate that the risk varies among asbestos- and erionite-exposed individuals because of their genetic background or because of exposure to other carcinogens. Moreover, these data provide a rationale for the observation that only a fraction of heavily exposed asbestos workers developed mesothelioma, and novel targets for prevention and therapy.}, } @article {pmid17044193, year = {2006}, author = {Mark, EJ and Kradin, RL}, title = {Pathological recognition of diffuse malignant mesothelioma of the pleura: the significance of the historical perspective as regards this signal tumor.}, journal = {Seminars in diagnostic pathology}, volume = {23}, number = {1}, pages = {25-34}, doi = {10.1053/j.semdp.2006.06.004}, pmid = {17044193}, issn = {0740-2570}, mesh = {*Asbestos/adverse effects/history ; Carcinogens/history ; History, 15th Century ; History, 16th Century ; History, 20th Century ; History, Ancient ; History, Medieval ; Humans ; Incidence ; *Mesothelioma/epidemiology/etiology/history/pathology ; *Pleural Neoplasms/epidemiology/etiology/history/pathology ; }, abstract = {Diffuse malignant mesothelioma (DMM) is a distinctive tumor which provides an uncommon opportunity to observe the gradual appreciation and increasing incidence of a new disease. DMM is a new disease. One cannot comment intelligently about the pathology of sporadic cases that might have occurred before the beginnings of anatomic pathology, but we do know that there were so few cases before 1930 that the very existence of the disease was not accepted in general before 1930 and not accepted by all pathologists even up until 1960. Because DMM is increasing on a worldwide basis and is making its appearance in the developing world, where it has not previously been diagnosed, appreciation of how the disease came to be noticed sheds light on its causation. As a signal tumor for exposure to asbestos, and knowing that all special exposures contribute to the development of the disease, knowledge of its continuing escalation underscores the importance of recognition of previously unimplicated or occult exposures for reasons of public health in both developed and developing countries.}, } @article {pmid17040286, year = {2006}, author = {Maeda, M and Hino, O}, title = {Molecular tumor markers for asbestos-related mesothelioma: serum diagnostic markers.}, journal = {Pathology international}, volume = {56}, number = {11}, pages = {649-654}, doi = {10.1111/j.1440-1827.2006.02024.x}, pmid = {17040286}, issn = {1320-5463}, mesh = {Animals ; Asbestos/*toxicity ; Biomarkers, Tumor/*blood ; Carcinogens/*toxicity ; Disease Models, Animal ; Enzyme-Linked Immunosorbent Assay ; GPI-Linked Proteins ; Membrane Glycoproteins/*blood ; Mesothelin ; Mesothelioma/*blood/diagnosis/etiology ; Pleural Neoplasms/*blood/diagnosis/etiology ; Rats ; }, abstract = {Mesothelioma is an aggressive tumor arising from the mesothelium, and is usually associated with previous exposure to asbestos. The incubation period of the tumor may be described as 30-40 years, and the prognosis is dismal. In addition to immunohistochemical markers, recently, serum markers for the diagnosis of mesothelioma have been reported as candidates. In contrast, the expression in renal carcinoma (ERC) gene has been discovered in the Eker rat model (Tsc2 gene mutant), which is a homolog of the human mesothelin/megakaryocyte potentiating factor gene, and a novel ELISA system (N-ERC/mesothelin) has been developed. It has also been found that N-ERC/mesothelin is very stable and plentiful in the blood. In the present paper the potential utility of molecular diagnostic markers is reviewed, including ELISA systems for asbestos-related mesothelioma.}, } @article {pmid17030547, year = {2007}, author = {Boffetta, P}, title = {Epidemiology of peritoneal mesothelioma: a review.}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {18}, number = {6}, pages = {985-990}, doi = {10.1093/annonc/mdl345}, pmid = {17030547}, issn = {0923-7534}, mesh = {*Environmental Exposure ; Humans ; Incidence ; Lung Neoplasms/epidemiology/etiology ; Mesothelioma/*epidemiology/etiology ; Peritoneal Neoplasms/*epidemiology/etiology ; Radiation, Ionizing ; Risk Factors ; }, abstract = {The epidemiology of peritoneal mesothelioma is complicated by possible geographic and temporal variations in diagnostic practices. The incidence rates in industrialized countries range between 0.5 and three cases per million in men and between 0.2 and two cases per million in women. Exposure to asbestos is the main known cause of peritoneal mesothelioma. Results on peritoneal mesothelioma have been reported for 34 cohorts exposed to asbestos, among which a strong correlation was present between the percentages of deaths from pleural and peritoneal mesothelioma (correlation coefficient 0.8, P < 0.0001). Studies of workers exposed only or predominantly to chrysotile asbestos resulted in a lower proportion of total deaths from peritoneal mesothelioma than studies of workers exposed to amphibole or mixed type of asbestos. Cases of peritoneal mesothelioma have also been reported following exposure to erionite and Thorotrast, providing further evidence of common etiological factors with the pleural form of the disease. The role of other suspected risk factors, such as simian virus 40 infection and genetic predisposition, is unclear at present. Control of asbestos exposure remains the main approach to prevent peritoneal mesothelioma.}, } @article {pmid17022390, year = {2006}, author = {Senkottaiyan, N and Seacord, LM and Fulling, KH and Birchem, JA and Fraley, MA and Alpert, MA}, title = {Sarcomatous pleural mesothelioma metastatic to left ventricular endocardium.}, journal = {Angiology}, volume = {57}, number = {4}, pages = {517-521}, doi = {10.1177/0003319706290737}, pmid = {17022390}, issn = {0003-3197}, mesh = {Aged ; Endocardium/pathology ; Heart Neoplasms/*pathology/secondary ; Heart Ventricles/pathology ; Humans ; Male ; Mesothelioma/*pathology ; Neoplasm Invasiveness ; Pleural Neoplasms/*pathology ; Sarcoma/*pathology ; }, abstract = {A 71-year-old man, a cigarette smoker with long-term asbestos exposure, developed multifocal malignant sarcomatous pleural mesothelioma that metastasized to the left ventricular endocardium without invading pericardium, myocardium, or the contiguous pulmonary vein. This is the first reported case of malignant pleural mesothelioma to metastasize in such a manner.}, } @article {pmid17017384, year = {2006}, author = {Mazzetti, L and Murer, B and Quintavalle, S and Zeni, E and Miotto, D and Mapp, CE and De Rosa, E and Boschetto, P}, title = {[Lung cancer in a female non-smoker with occupational exposure to asbestos: a case report].}, journal = {La Medicina del lavoro}, volume = {97}, number = {4}, pages = {581-585}, pmid = {17017384}, issn = {0025-7818}, mesh = {Asbestos/*adverse effects ; Female ; Humans ; Lung Neoplasms/*etiology ; Middle Aged ; Occupational Exposure/*adverse effects ; }, abstract = {BACKGROUND: Until recently, asbestos was widely used in a variety of industrial processes. Workers exposed to asbestos may develop lung and pleural diseases such as asbestosis, lung cancer, benign pleural effusion, pleural plaques and mesothelioma.

OBJECTIVE: To describe a clinical case of lung cancer in a female non-smoker with occupational exposure to asbestos.

METHODS: The clinical and occupational history was based on the information kindly provided by the Occupational Unit of the National Health Service and on the case history of a hospital admittance in 2001, when the patient underwent surgery for lung cancer.

RESULTS: The patient worked for 6 years in an asbestos manufacturing industry where she was exposed to high concentrations of asbestos, and then worked for 14 years in a sugar refinery only during the summer. She had benign pleural effusion, pleural plaques, asbestosis and lung cancer.

CONCLUSIONS: We concluded that a six-year exposure to high doses of asbestos may induce lung cancer and asbestosis in a female non-smoker.}, } @article {pmid17017375, year = {2006}, author = {Terracini, B}, title = {The scientific basis of a total asbestos ban.}, journal = {La Medicina del lavoro}, volume = {97}, number = {2}, pages = {383-392}, pmid = {17017375}, issn = {0025-7818}, mesh = {Animals ; Asbestos/*adverse effects/classification/toxicity ; Carcinogenicity Tests ; Carcinogens, Environmental/adverse effects/toxicity ; Cocarcinogenesis ; Cohort Studies ; Cricetinae ; Developing Countries ; Environmental Exposure ; European Union ; Evidence-Based Medicine ; Female ; Genetic Predisposition to Disease ; Global Health ; Hazardous Substances/*adverse effects/toxicity ; Humans ; Lung/chemistry ; Lung Neoplasms/etiology ; Male ; Mesothelioma/epidemiology/etiology/genetics/prevention & control/virology ; Mice ; Mineral Fibers/adverse effects ; Occupational Diseases/epidemiology/etiology/prevention & control ; Occupational Exposure ; Pleural Neoplasms/epidemiology/etiology/genetics/prevention & control/virology ; Rats ; Risk ; Simian virus 40/pathogenicity ; Time Factors ; }, abstract = {Worldwide, in the new millennium, standards for the protection of workers and the general population from as-bestos risks are not equally stringent in all countries. The present review analyzes some arguments which in recent years have been proposed as a rationale for the reconsideration of the scientific background of a total asbestos ban, such as that adopted in the European Union. The conclusion is that in order to ensure adequate protection, there is no alternative to a total ban. The evidence for carcinogenicity of chrysotile is as good as for the amphiboles, the carcinogenic potency of chrysotile is lower than that of the amphiboles, but risk estimates must also be based on extent of exposure (nowadays chrysotile represents 95% of asbestos used worldwide). The fact that induction of mesothelioma by asbestos results from the interaction of environmental exposure and genetic factors reflects a general phenomenon in carcinogenesis and does not warrant any re-consideration of the role of asbestos. The role of SV40 as yet is unclear: even assuming that current risk estimates are correct (which is debatable), this agent would interact with asbestos in only a faction of mesothelioma cases. The effectiveness of protocols suggested for "controlled use" has not been tested with a scientfiic approach: they seem hardly practicable, particularly in the countries which are currently the major consumers of asbestos.}, } @article {pmid17013496, year = {2006}, author = {Tanrikulu, AC and Senyigit, A and Dagli, CE and Babayigit, C and Abakay, A}, title = {Environmental malignant pleural mesothelioma in Southeast Turkey.}, journal = {Saudi medical journal}, volume = {27}, number = {10}, pages = {1605-1607}, pmid = {17013496}, issn = {0379-5284}, mesh = {Asbestos/*adverse effects ; *Carcinogens, Environmental ; *Environmental Exposure ; Female ; Humans ; Male ; Mesothelioma/chemically induced/diagnostic imaging/*epidemiology ; Middle Aged ; Pleural Neoplasms/chemically induced/diagnostic imaging/*epidemiology ; Radiography ; Turkey/epidemiology ; }, } @article {pmid17009684, year = {2006}, author = {Marinaccio, A and Branchi, C and Massari, S and Scarselli, A}, title = {National epidemiologic surveillance systems of asbestos-related disease and the exposed workers register.}, journal = {La Medicina del lavoro}, volume = {97}, number = {3}, pages = {482-487}, pmid = {17009684}, issn = {0025-7818}, mesh = {Aged ; Asbestos/*adverse effects ; Asbestosis/*epidemiology ; Female ; Humans ; Italy ; Lung Neoplasms/*epidemiology/etiology ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Exposure/adverse effects/*statistics & numerical data ; *Population Surveillance ; *Registries ; }, abstract = {INTRODUCTION: Italy was the main European producer of asbestos for most of the 20th century and raw asbestos imports wee also significant until the 1990's; there was a mean delay of about ten years in the pattern of asbestos consumption in Italy compared with the USA, Australia, UK and Scandinavian countries.

METHODS: A national surveillance system (ReNaM) was implemented to identify cases of mesothelioma and investigate the modalities of asbestos exposure. A register of exposed workers and a database of companies presumably involved in the asbestos exposure problem was also developed. ReNaM has a regional structure and an operative centres (COR) have been established in 16 Italian regions.

RESULTS: The ReNaM database currently contains more than 5,000 mesothelioma cases and for 3,500 of these exposure modalities have been defined. Cases of pleural mesothelioma represent 93% of the total but there were also 334 cases of peritoneal mesothelioma, 15 of the pericardium and 14 of the tunica vaginalis of the testicle. Cases with ascertained exposure are thus distributed: 67.4% occupational exposure (ascertained, probable, possible), 4.3% domestic, 4.2% environmental and 1.3% hobby-related exposure, totalling 77.2%; 22.8% had unlikely or unknown exposure. The latency period is very long: on average 43.6 years. The register of asbestos-exposed workers contains figures on exposed workers notified to ISPESL up to 2004 and refers to the exposure period 1993-2003. The data registered cover 160 firms and about 700 workers.

CONCLUSIONS: A national, coordinated and uniform epidemiological surveillance system of cases of mesothelioma and the definition of asbestos exposure through active research is extremely important in identifying unexpected contaminating sources. The register of asbestos-exposed workers allows risk to be monitored and protection measures to be implemented.}, } @article {pmid17009682, year = {2006}, author = {Governa, M and Amati, M and Bellis, D and Bichisecchi, E and Santarelli, L}, title = {Diagnosis of asbestos-related pleuropolmonary diseases.}, journal = {La Medicina del lavoro}, volume = {97}, number = {3}, pages = {463-474}, pmid = {17009682}, issn = {0025-7818}, mesh = {Asbestos/*adverse effects ; Asbestosis/*diagnosis ; Humans ; Lung Neoplasms/*diagnosis/*etiology ; Mesothelioma/*diagnosis/*etiology ; Pleural Diseases/*diagnosis/*etiology ; Tomography, X-Ray Computed ; }, abstract = {A revision of criteria for diagnosis of asbestos-related pathological conditions was performed studying specially asbestosis, pleural plaques and malignant mesothelioma, also taking into account the problems connected with histopathology. As regards the histological diagnosis of asbestosis, it requires the presence of diffuse interstitialfibrosis in a well inflated tissue remote from the site of a tumour or other large lesion, plus the presence of two or more asbestos bodies in a 1 cm2 section. As regards the imaging diagnosis, the HRTC 4-point scale proposed by Paris et al. (2004) has been adopted:--0 images not suggestive of interstitial pneumonia;--1 modest unilateral or bilateral interstitial abnormalities, involving restricted areas if bilateral;--2 interstitial abnormalities of limited extent, but consistent with a diagnosis of asbestosis, i.e. honeycombing, even without other parenchymal changes and even though unilateral, or else any two abnormal findings among thickened interlobular septa, intralobular lines or subpleural curved lines;--3 numerous bilateral changes on several slices involving more than 2/3 of the posterior third of each hemi thorax. Only points 2 and 3 were considered consistent with the diagnosis of lung fibrosis. Such HRCT findings are not specific for asbestosis, changes in the pleural wall such as diffuse plaques and thickenings contribute to the diagnosis of asbestosis. As regards the pleural plaques and asbestos bodies we remark that they are merely exposition markers. We also discussed the problems the pathologist may encounter in diagnosing mesothelioma; in this field the prospects are encouraging as microarray analysis are beginning to identify new molecular markers for mesothelioma.}, } @article {pmid17009680, year = {2006}, author = {Masi, M}, title = {Point of view of Italian regions.}, journal = {La Medicina del lavoro}, volume = {97}, number = {3}, pages = {453-457}, pmid = {17009680}, issn = {0025-7818}, mesh = {*Asbestosis/prevention & control ; Humans ; Italy ; *Lung Neoplasms/prevention & control ; *Mesothelioma/prevention & control ; Population Surveillance ; }, abstract = {The tragic chain of mortal events, that have happened to workers and people who have been exposed to asbestos, proposes clearly an accentuation of the efforts that have been undertaken up to now, even in absence of precise national directives, in order to give an answer to worries and, sometimes, to real consequences of citizens' and workers' asbestos exposure. Region of Tuscany, following the initiatives which have been carried out in national and regional field for the formerly asbestos-exposed or other carcinogenic agents workers, performed a guideline that was just titled "Guidelines on sanitary surveillance of formerly exposed to occupational carcinogens workers". The debate, which had risen around the sanitary surveillance of the formerly-exposed to occupational carcinogenic agents workers, had induced indeed many institutions to take decisions on issues which were not yet explicitly regulated by the national law. For example the guidelines provided suggestions regarding what bodies--either public or private--should be appointed to this task, or the kind of protocols should be adopted with all the related collective and individual consequences.}, } @article {pmid17009677, year = {2006}, author = {Mensi, C and Canti, Z and Rivolta, G and Riboldi, L and Chiappino, G}, title = {[Malignant mesothelioma in the maritime professions].}, journal = {La Medicina del lavoro}, volume = {97}, number = {1}, pages = {82}, pmid = {17009677}, issn = {0025-7818}, mesh = {Asbestos/*adverse effects ; Asbestosis/*complications ; Humans ; Italy/epidemiology ; Mesothelioma/*epidemiology/etiology ; *Naval Medicine ; Occupational Diseases/*epidemiology/etiology ; Pleural Neoplasms/*epidemiology/etiology ; }, } @article {pmid17009671, year = {2006}, author = {Barbieri, PG and Silvestri, S and Veraldi, A and Festa, R and Martello, F and Garattini, S}, title = {[Pleural mesothelioma in cotton spinning workers].}, journal = {La Medicina del lavoro}, volume = {97}, number = {1}, pages = {51-57}, pmid = {17009671}, issn = {0025-7818}, mesh = {Aged ; Aged, 80 and over ; *Cotton Fiber ; Female ; Humans ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Occupational Diseases/*epidemiology ; Occupational Exposure/*statistics & numerical data ; Pleural Neoplasms/*epidemiology ; }, abstract = {BACKGROUND: Cases of malignant mesothelioma (MM) in the non-asbestos textile industry have recently been described, but asbestos exposure in spinning and looming has seldom been reported. Nevertheless, on a national level the Italian Mesothelioma Registry (Re.Na.M) contains numerous cases of MM with past non-asbestos textile work but classified as "unknown" exposure due to poor information.

OBJECTIVES: The aim of this research was to investigate possible past occupational exposure to asbestos in this specific industrial sector.

METHODS: The MM cases were collected from the Mesothelioma Registry of Brescia. Work histories were obtained via a standardized questionnaire. Investigations were conducted in textile machinery manufacturing plants in order to collect information regarding the possible use of asbestos parts; at the same time, the use of asbestos friction materials and the use of sprayed asbestos for noise abatement purposes or thermal insulation was checked in the cotton industry by interviewing the management of two companies where a cluster of MM was observed.

RESULTS: The Mesothelioma Registry of Brescia retrieved and collected 15 MM cases with past work in the cotton spinning industry, 4 of them employed in the same company. Further search of asbestos use gave positive results as the use of friction materials has been widespread since the fifties, while sprayed asbestos was not found anywhere in the cotton industry. On the other hand, half of the cases were employed during the thirties and forties, when friction materials appear to have been asbestos-free. Therefore the other hypothesis of exposure could be direct manufacture of asbestos yarn.

CONCLUSION: The results of this investigation indicate the attribution, at least, of possible asbestos exposure"for those cases employed in textile industries since the fifties, according to the Re.Na.M guidelines; for those cases employed before that period the same classification can be attributed on an epidemiological basis. Previous work periods need further investigation in order to demonstrate the circumstances of the occupational asbestos exposure, given the heterogeneity of work processes and machinery characteristic of this industrial sector.}, } @article {pmid17008483, year = {2006}, author = {Chhajed, PN and Bubendorf, L and Hirsch, H and Boehler, A and Weder, W and Tamm, M}, title = {Mesothelioma after lung transplantation.}, journal = {Thorax}, volume = {61}, number = {10}, pages = {916-917}, pmid = {17008483}, issn = {0040-6376}, mesh = {Female ; Hemorrhage/etiology ; Humans ; Lung Transplantation/*adverse effects ; Mesothelioma/*etiology ; Middle Aged ; Pleural Effusion/etiology ; Pulmonary Fibrosis/surgery ; }, abstract = {The case history is presented of a lung transplant recipient who developed malignant mesothelioma. This is thought to be the first such report. Mesothelioma should be suspected in lung transplant recipients with a haemorrhagic pleural effusion in the native lung when there is no convincing evidence for bronchogenic carcinoma or post transplant lymphoproliferative disease, even in the absence of exposure to asbestos.}, } @article {pmid16989994, year = {2006}, author = {Zucali, PA and Giaccone, G}, title = {Biology and management of malignant pleural mesothelioma.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {42}, number = {16}, pages = {2706-2714}, doi = {10.1016/j.ejca.2006.07.011}, pmid = {16989994}, issn = {0959-8049}, mesh = {Antineoplastic Agents/therapeutic use ; Apoptosis ; Combined Modality Therapy ; Forecasting ; Humans ; *Mesothelioma/genetics/pathology/therapy ; Neovascularization, Pathologic/genetics/pathology ; *Pleural Neoplasms/genetics/pathology/therapy ; }, abstract = {Malignant mesothelioma is an aggressive tumour, with a poor prognosis and an increasing incidence as a result of widespread exposure to asbestos. The results of the treatments available are poor. Surgery and radiotherapy have a limited role in highly selected patients and systemic therapy is the only potential treatment option for the majority of patients. Despite some definite activity of the novel antifolates such as pemetrexed and raltitrexed, the results, even in combination with platinating agents, are still modest, with a median survival of approximately one year. The better understanding of the biology of mesothelioma makes the assessment of a number of targeted agents particularly interesting. Unfortunately, the targeted agents imatinib, gefitinib, erlotinib and thalidomide have been shown to be ineffective in unselected patients. Studies with anti-angiogenesis agents are ongoing. An improvement of the knowledge of major molecular pathways involved in malignant mesothelioma is needed in order to define proper targets for the systemic treatment of this disease.}, } @article {pmid16989168, year = {2005}, author = {Ewa, SW and Renata, L}, title = {[Malignant pleural mesothelioma--histopathological classification, staging and microscopic diagnosis].}, journal = {Pneumonologia i alergologia polska}, volume = {73}, number = {3}, pages = {285-291}, pmid = {16989168}, issn = {0867-7077}, mesh = {Asbestos/toxicity ; Humans ; Immunohistochemistry ; Mediastinal Neoplasms/*classification/etiology/*pathology/therapy ; Mesothelioma/*classification/etiology/*pathology/therapy ; Neoplasm Staging ; Pleural Effusion, Malignant/diagnostic imaging/pathology/therapy ; Pleural Neoplasms ; Radiography, Thoracic/methods ; Sensitivity and Specificity ; Tomography, X-Ray Computed ; }, } @article {pmid16984904, year = {2006}, author = {McDonald, JC and Harris, JM and Berry, G}, title = {Sixty years on: the price of assembling military gas masks in 1940.}, journal = {Occupational and environmental medicine}, volume = {63}, number = {12}, pages = {852-855}, pmid = {16984904}, issn = {1470-7926}, mesh = {Asbestos, Crocidolite/*toxicity ; Cause of Death ; Cohort Studies ; England/epidemiology ; Female ; Humans ; Male ; Mesothelioma/etiology/mortality ; Neoplasms/epidemiology/*etiology ; Occupational Diseases/*etiology/mortality ; Occupational Exposure/adverse effects/analysis ; *Respiratory Protective Devices ; }, abstract = {BACKGROUND: Between 1940 and 1944 military gas masks with filter pads containing 20% crocidolite were assembled in a Nottingham factory.

METHODS: Records supplied by the late Professor Stephen Jones were of 1154 persons, mainly women, who had worked in the factory during this period; they included many deaths from mesothelioma. A systematic effort was therefore made to establish causes of death for the whole cohort.

RESULTS: Of 640 employees with full name and sex recorded, 567 (89%) were traced. Of these, 491 had died, including 65 from mesothelioma, though only 54 were certified as such. After exclusion of these 54, standardised mortality ratios were significantly raised for respiratory cancer (SMR 2.5) and carcinomatosis (SMR 3.2). The pattern of mortality in the remaining 514 employees without full identification was similar, but a low tracing rate (40%) did not justify their further analysis. The first death from mesothelioma was in 1963 (22 years after first exposure) and the last in 1994, whereas a further 5.0 cases would have been expected between 1996 and 2003 (p = 0.0065).

CONCLUSION: These findings in a cohort followed over 60 years after brief exposure to crocidolite confirm a high and specific risk of mesothelioma (28% peritoneal) and perhaps of lung cancer some 20-50 years later. The statistically significant absence of further mesothelioma cases during the past eight years suggests that crocidolite, though durable, is slowly removed.}, } @article {pmid16983974, year = {2005}, author = {Bianchi, C and Bianchi, T and Grandi, G}, title = {Malignant mesothelioma of the pleura among seafarers.}, journal = {La Medicina del lavoro}, volume = {96}, number = {6}, pages = {490-495}, pmid = {16983974}, issn = {0025-7818}, mesh = {Age Factors ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Asbestosis/*complications/epidemiology/pathology ; Autopsy ; Humans ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology/etiology/pathology ; Middle Aged ; *Naval Medicine ; Occupational Diseases/*epidemiology/etiology/pathology ; Occupational Exposure/*adverse effects ; Pleura/pathology ; Pleural Neoplasms/*epidemiology/etiology/pathology ; Risk Factors ; }, abstract = {BACKGROUND: A large amount of data indicates that seafarers are at risk for asbestos disease.

OBJECTIVES: To trace the outlines of pleural mesothelioma among seafarers.

METHODS: Pleural mesotheliomas diagnosed among seamen in the Trieste-Monfalcone area, Italy, in the period 1973-2003, were reviewed.

RESULTS: The series comprised 50 men aged between 53 and 91 years (mean age 75.7 years). The diagnosis of mesothelioma was confirmed by necropsy in 38 cases. The patients had served in the Italian Navy (24 persons), in the merchant navy (17 persons), or in both (9 persons). The trades were various including engine room as well as deck personnel. Asbestos bodies were detected on routine lung sections in 55% of the necropsy cases. Asbestos bodies isolated from the lungs in three cases ranged between 2100 and 7000 bodies per gram of dried tissue. Latency periods ranged between 33 and 72 years (mean 56.1 years).

CONCLUSIONS: When compared with shipyard workers, the seamen with mesothelioma show signs of less intense exposure to asbestos, and longer latency periods. Mesothelioma in seamen should be considered as an occupational disease.}, } @article {pmid16972515, year = {2006}, author = {McCulloch, J}, title = {Saving the asbestos industry, 1960 to 2006.}, journal = {Public health reports (Washington, D.C. : 1974)}, volume = {121}, number = {5}, pages = {609-614}, pmid = {16972515}, issn = {0033-3549}, mesh = {Asbestos/adverse effects/economics/*history ; Asbestosis/*history ; Canada ; History, 20th Century ; History, 21st Century ; Humans ; Jurisprudence/history ; Lung Neoplasms/*history ; Mesothelioma/*history ; Mineral Fibers ; Mining/history ; Occupational Diseases/history ; South Africa ; United Kingdom ; United States ; }, } @article {pmid16969013, year = {2006}, author = {Nakano, T}, title = {[Malignant mesothelioma--diagnosis and treatment strategies].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {33}, number = {9}, pages = {1215-1220}, pmid = {16969013}, issn = {0385-0684}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Asbestos/adverse effects ; Camptothecin/administration & dosage/analogs & derivatives ; Cisplatin/administration & dosage ; Clinical Trials, Phase III as Topic ; Combined Modality Therapy ; Deoxycytidine/administration & dosage/analogs & derivatives ; Drug Administration Schedule ; Humans ; Interleukin-6/biosynthesis ; Irinotecan ; Mediastinal Neoplasms/*diagnosis/surgery/*therapy ; Mesothelioma/*diagnosis/surgery/*therapy ; Pleural Neoplasms/diagnosis/surgery/therapy ; Tomography, X-Ray Computed ; Gemcitabine ; }, abstract = {Malignant mesothelioma originates from the mesothelial cells of the pleural and peritoneal cavities as well as the pericardium and tunica vaginalis, which is a devastating neoplasm with a strong etiological relationship with asbestos exposure. The incidence is rising worldwide, with the peak incidence in most industrialized counties expected to occur in the year 2020. Given the disappointing results of the single standard therapeutic modality, the combination of extrapleural pneumonectomy, chemotherapy, and radiotherapy has been attempted in order to reduce local recurrence and distal spread. Combined modalities have a better prognosis in selected patients with epithelioid histology, clear resection margins, and no positive extrapleural nodes. Chemotherapy using new antimetabolite agents in combination with platinum compounds is useful for palliation and can improve both survival and quality of life compared with single-agent cisplatin.}, } @article {pmid16967841, year = {2006}, author = {Egilman, DS and Billings, MA}, title = {Differential peeky bias.}, journal = {International journal of occupational and environmental health}, volume = {12}, number = {3}, pages = {294}, doi = {10.1179/oeh.2006.12.3.294}, pmid = {16967841}, issn = {1077-3525}, mesh = {Asbestos/*adverse effects ; Automobiles ; Causality ; Evaluation Studies as Topic ; Humans ; Industry ; Mesothelioma/etiology ; Occupational Diseases/epidemiology/*etiology ; Occupational Exposure/*adverse effects/statistics & numerical data ; Science/methods ; }, } @article {pmid16967840, year = {2006}, author = {Paustenbach, DJ}, title = {Scientific method questioned.}, journal = {International journal of occupational and environmental health}, volume = {12}, number = {3}, pages = {290-2; author reply 292-3}, doi = {10.1179/oeh.2006.12.3.290}, pmid = {16967840}, issn = {1077-3525}, mesh = {Asbestos/adverse effects ; Automobiles ; Causality ; Conflict of Interest ; Editorial Policies ; *Epidemiologic Studies ; Humans ; Industry ; Mesothelioma/etiology ; Occupational Diseases/etiology/*prevention & control ; Peer Review/*ethics/methods ; Professional Competence ; *Research Design ; Science/methods ; }, } @article {pmid16967832, year = {2006}, author = {Pandita, S}, title = {Banning asbestos in Asia: campaigns and strategies by the Asian Network for the Rights of Occupational Accident Victims (ANROAV).}, journal = {International journal of occupational and environmental health}, volume = {12}, number = {3}, pages = {248-253}, doi = {10.1179/oeh.2006.12.3.248}, pmid = {16967832}, issn = {1077-3525}, mesh = {Asbestos/*adverse effects ; Asbestosis/*prevention & control ; Asia ; Communication ; Hazardous Substances/*standards ; Humans ; Mesothelioma/diagnosis/etiology/prevention & control ; Occupational Exposure/prevention & control/*standards ; Public Health ; *Public Policy ; }, abstract = {China, India, Indonesia, and Thailand are among the largest consumers of asbestos. Because markets in the West are dwindling, asbestos is heavily promoted in Asia. In spite of widespread usage, asbestos-related diseases are surprisingly few and reported cases of mesothelioma are rare in Asia except in Japan, Korea, and Singapore. The problem lies in diagnosis. Most of the asbestos-related diseases are not diagnosed in Asia and thus do not appear in government statistics. This deadly substance is killing workers. Unless drastic action is taken to stop its use, Asian workers as well as the general population will pay a heavy price.}, } @article {pmid16966607, year = {2006}, author = {Kroczynska, B and Cutrone, R and Bocchetta, M and Yang, H and Elmishad, AG and Vacek, P and Ramos-Nino, M and Mossman, BT and Pass, HI and Carbone, M}, title = {Crocidolite asbestos and SV40 are cocarcinogens in human mesothelial cells and in causing mesothelioma in hamsters.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {103}, number = {38}, pages = {14128-14133}, pmid = {16966607}, issn = {0027-8424}, support = {P01 CA114047/CA/NCI NIH HHS/United States ; R01 CA092657/CA/NCI NIH HHS/United States ; R01 CA106567/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Asbestos, Crocidolite/metabolism/*toxicity ; *Carcinogens/metabolism/toxicity ; Cells, Cultured ; Cricetinae ; Enzyme Activation ; Epithelial Cells/cytology/*metabolism ; Epithelium/*metabolism/pathology ; Female ; Gene Expression Regulation, Enzymologic ; *Gene Expression Regulation, Neoplastic ; Humans ; Matrix Metalloproteinase 1/genetics/metabolism ; Matrix Metalloproteinase 9/genetics/metabolism ; Mesocricetus ; *Mesothelioma/etiology/metabolism/pathology ; Mitogen-Activated Protein Kinase 1/genetics/metabolism ; Mitogen-Activated Protein Kinase 3/genetics/metabolism ; Proto-Oncogene Proteins c-fos/genetics/metabolism ; RNA, Small Interfering/metabolism ; Repressor Proteins/genetics/metabolism ; Simian virus 40/metabolism/*pathogenicity ; Transcription Factor AP-1/genetics/metabolism ; Transcriptional Activation ; }, abstract = {Only a fraction of subjects exposed to asbestos develop malignant mesothelioma (MM), suggesting that additional factors may render some individuals more susceptible. We tested the hypothesis that asbestos and Simian virus (SV40) are cocarcinogens. Asbestos and SV40 in combination had a costimulatory effect in inducing ERK1/2 phosphorylation and activator protein-1 (AP-1) activity in both primary Syrian hamster mesothelial cells (SHM) and primary human mesothelial cells (HM). Ap-1 activity caused the expression and activation of matrix metalloprotease (MMP)-1 and MMP-9, which in turn led to cell invasion. Experiments using siRNA and chemical inhibitors confirmed the specificity of these results. The same effects were observed in HM and SHM. Experiments in hamsters showed strong cocarcinogenesis between asbestos and SV40: SV40 did not cause MM, asbestos caused MM in 20% of hamsters, and asbestos and SV40 together caused MM in 90% of hamsters. Significantly lower amounts of asbestos were sufficient to cause MM in animals infected with SV40. Our results indicate that mineral fibers and viruses can be cocarcinogens and suggest that lower amounts of asbestos may be sufficient to cause MM in individuals infected with SV40.}, } @article {pmid16965949, year = {2006}, author = {Musti, M and Kettunen, E and Dragonieri, S and Lindholm, P and Cavone, D and Serio, G and Knuutila, S}, title = {Cytogenetic and molecular genetic changes in malignant mesothelioma.}, journal = {Cancer genetics and cytogenetics}, volume = {170}, number = {1}, pages = {9-15}, doi = {10.1016/j.cancergencyto.2006.04.011}, pmid = {16965949}, issn = {0165-4608}, mesh = {Asbestos/toxicity ; Chromosome Deletion ; DNA Damage ; Genes, Tumor Suppressor ; Genes, p16 ; Growth Substances/metabolism ; Humans ; Mesothelioma/chemically induced/*genetics/metabolism ; }, abstract = {Malignant mesothelioma (MM) results from the accumulation of a number of acquired genetic events, especially deletions, which lead to the inactivation of multiple onco-suppressor genes in a multistep cascade mechanism. Past asbestos exposure represents the major risk factor for MM, and the link between asbestos fibers and MM has been largely proved by several epidemiologic and experimental studies. Asbestos fibers induce DNA and chromosomal damage. Most MM cases have shown multiple chromosomal abnormalities. Chromosomal losses are more common than gains. The most common cytogenetic abnormality in MM is a deletion in 9p21, the locus of CDKN2A, a tumor suppressor gene (TSG). The deletion of CDKN2A is a negative prognostic factor in MM. Loss of TSG CDKN2A/p14(ARF) is also common in MM and mutations in NF2 occur in approximately half of the cases. Despite the ban on asbestos use in Western countries, the incidence of MM is increasing, and asbestos is still used in developing countries. This epidemiologic situation calls for further research. Ongoing studies are already applying high-throughput genomic profiling methods in MM. Genetic alterations observed in MM may be useful in differential diagnosis between lung cancer and MM, as diagnostic markers or therapeutic targets, and as indicators of premalignancy for primary prevention and health surveillance.}, } @article {pmid16956157, year = {2006}, author = {Musk, AW and Olsen, NJ and Reid, A and Threlfall, T and de Klerk, NH}, title = {Asbestos-related disease from recycled hessian superphosphate bags in rural Western Australia.}, journal = {Australian and New Zealand journal of public health}, volume = {30}, number = {4}, pages = {312-313}, doi = {10.1111/j.1467-842x.2006.tb00840.x}, pmid = {16956157}, issn = {1326-0200}, mesh = {Asbestos/*adverse effects/metabolism ; *Diphosphates ; Female ; *Fertilizers ; Humans ; Middle Aged ; Occupational Exposure ; Pleural Diseases/etiology ; *Product Packaging ; Western Australia ; }, abstract = {OBJECTIVES: To describe the dissemination of asbestos fibres within the Western Australian community.

METHODS: A case report.

RESULTS: A 60-year-old female was referred for investigation of calcified pleural plaques. On questioning, she recalled exposure to asbestos as a child on the family farm. She had shaken hessian bags prior to recycling to the fertiliser supplier. Her father survived to 90 years. Her mother died from malignant pleural mesothelioma. Four of five siblings had shaken the bags, two had radiographic evidence of pleural plaques while two others had not had recent chest x-rays.

CONCLUSIONS: It appears that the use of recycled hessian bags for the fertiliser industry was endemic in the State during the period 1943-66. It is possible that many farmers and their families have had similar exposure to asbestos.

IMPLICATIONS: The risk of developing an asbestos-related disease is not restricted to any specific social or employment groups within the Australian community.}, } @article {pmid16925806, year = {2006}, author = {Tug, E and Tug, T and Elyas, H and Coskunsel, M and Emri, S}, title = {Tumor suppressor gene alterations in patients with malignant mesothelioma due to environmental asbestos exposure in Turkey.}, journal = {Journal of carcinogenesis}, volume = {5}, number = {}, pages = {23}, pmid = {16925806}, issn = {1477-3163}, abstract = {BACKGROUND: Environmental asbestos exposure can cause the grave lung and pleura malignancies with a high mortality rate, and it is also associated with increased rate of other organ malignancies. Asbestos exposure can develop genotoxic effects and damage in the pleura and lungs.

OBJECTIVE: In this study, we aimed to determine tumor suppressor gene (TSG) loss in genomic DNA which was isolated from pleural fluid and blood samples of patients with Malignant Pleural Mesothelioma (MPM) due to environmental asbestos exposure.

DESIGN AND PATIENTS: Prospective study of period from 2001 to 2003 in 17 patients with MPM.

METHODS: A total of 12 chromosomal regions were researched by comparing genomic DNA samples isolated from blood and pleural effusion (using PCR, and polyacrylamide gel electrophoresis denaturizing), on 2 different chromosomes which have 9 different polymorphic determinants at 6q and 3 different polymorphic determinants at 9p using molecular genetic methods on 13 patients clinico-pathologically diagnosed MPM.

RESULTS: Loss of Heterozygosity (LOH) was determined at D6S275 in one patient, at D6S301 in another, at D6S474 in 2, at ARG1 in 2, at D6S1038 in 2 and at D6S1008 in 3 patients. In 7 (54%) of the 13 patients, we found LOH in at least one site. No LOH was determined at any informative loci in 6 patients. Of the 13 patients, no investigated markers were determined at 9p.

CONCLUSION: In this study, genomic DNA samples obtained from MPM patients with asbestos exposure revealed that they contained important genotoxic damage. We found no other study on this subject at molecular level in pleural effusion either in Turkey or in the Med-line literature. We believe that this study will provide important support for other research into molecular-genetic variations, both on this subject and other malignancies, and may also constitute a base for early diagnosis and gene therapy research in the future.}, } @article {pmid16920675, year = {2006}, author = {Kane, AB}, title = {Animal models of malignant mesothelioma.}, journal = {Inhalation toxicology}, volume = {18}, number = {12}, pages = {1001-1004}, doi = {10.1080/08958370600835393}, pmid = {16920675}, issn = {1091-7691}, support = {R01 ES03721/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Cocarcinogenesis ; Cricetinae ; Gene Deletion ; Genetic Predisposition to Disease ; Humans ; Mesothelioma/*etiology/pathology ; Mice ; *Mice, Transgenic ; *Neoplasms, Experimental ; Peritoneal Neoplasms/*etiology/pathology ; Pleural Neoplasms/*etiology/pathology ; Polyomavirus Infections ; Rats ; Simian virus 40 ; Tumor Virus Infections ; }, abstract = {Animal models of diffuse malignant mesothelioma have historically been used to assess carcinogenicity of various fiber types and to study the pathogenesis of this unusual neoplasm. Pleural and peritoneal mesotheliomas have been induced in rodents following exposure to erionite or asbestos fibers, radionuclides, particulate nickel compounds, and chemicals such as 3-methylcholanthrene. The role of SV40 virus as a cofactor with asbestos fibers in the development of diffuse malignant mesotheliomas in humans has been explored in animal models. SV40 virus alone induces mesotheliomas in hamsters. Generation of new transgenic mouse strains with targeted expression of SV40 large T and small t antigens in the mesothelium would be very useful for mechanistic studies. Human malignant mesotheliomas frequently show hypermethylation or deletions at the Cdkn2a/Arf and Cdkn2b gene loci and deletions or mutations at the NF2 gene locus. Heterozygous Nf2 (+/-) mice exposed to crocidolite asbestos fibers exhibited accelerated development of malignant mesotheliomas compared to wild-type littermates. Loss of the wild-type Nf2 allele, leading to biallelic inactivation, was observed in nine mesothelioma cell lines derived from Nf2 (+/-) mice. Similar to human malignant mesotheliomas, tumors from Nf2 (+/-) mice showed frequent homozygous deletions of the Cdkn2a/Arf locus and adjacent Cdkn2b tumor suppressor gene. As in the human disease, murine mesotheliomas also showed constitutive activation of Akt. This murine model of asbestos carcinogenesis recapitulates the molecular and histopathological features of the human disease and has significant implications for preclinical testing of novel preventive or therapeutic modalities.}, } @article {pmid16920674, year = {2006}, author = {Pershouse, MA and Heivly, S and Girtsman, T}, title = {The role of SV40 in malignant mesothelioma and other human malignancies.}, journal = {Inhalation toxicology}, volume = {18}, number = {12}, pages = {995-1000}, doi = {10.1080/08958370600835377}, pmid = {16920674}, issn = {1091-7691}, support = {P20RR017670/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Asbestos/adverse effects ; Carcinogens, Environmental/adverse effects ; *Cocarcinogenesis ; Cricetinae ; Disease Models, Animal ; Humans ; Mesothelioma/*etiology ; Mice ; Mice, Transgenic ; Polyomavirus Infections/*complications ; Simian virus 40/isolation & purification/*pathogenicity/physiology ; Tumor Virus Infections/*complications ; }, abstract = {SV40 is a DNA tumor virus thrust upon human populations primarily as a contaminant in various vaccine preparations. Some estimates suggest that millions of people are currently infected with the virus. The virus causes primary brain tumors, bone tumors, lymphomas, and mesotheliomas when injected into some rodent models. It has also been detected in a similar spectrum of human tumors. However, epidemiological studies have failed to conclusively demonstrate a higher incidence of disease in affected populations. To date, over 60 reports from 49 different laboratories have shown SV40 sequences in tissues from human cancer patients. Six studies, however, have failed to detect evidence of virus in similar tissues. Some have suggested that SV40 may act as a cocarcinogen with asbestos to cause mesothelioma formation, or that it may be responsible for the 10-20% of mesotheliomas with no reported history of asbestos exposure. This report briefly covers the historical evidence for SV40 carcinogenesis and then covers experiments now underway to better understand the role of SV40 in human mesotheliomas.}, } @article {pmid16920672, year = {2006}, author = {Hei, TK and Xu, A and Huang, SX and Zhao, Y}, title = {Mechanism of fiber carcinogenesis: from reactive radical species to silencing of the beta igH3 gene.}, journal = {Inhalation toxicology}, volume = {18}, number = {12}, pages = {985-990}, doi = {10.1080/08958370600835310}, pmid = {16920672}, issn = {1091-7691}, support = {ES 05786/ES/NIEHS NIH HHS/United States ; ES 09089/ES/NIEHS NIH HHS/United States ; ES 11804/ES/NIEHS NIH HHS/United States ; P42 ES 10349/ES/NIEHS NIH HHS/United States ; }, mesh = {Asbestos/*adverse effects ; Carcinogens, Environmental/*adverse effects ; Cells, Cultured ; Cocarcinogenesis ; Environmental Exposure/adverse effects ; Extracellular Matrix Proteins/*genetics/metabolism ; Gene Expression Regulation, Neoplastic/*drug effects ; Mineral Fibers/adverse effects ; Mutagens/*adverse effects ; Respiratory Tract Diseases/*genetics/pathology ; Transforming Growth Factor beta/*genetics/metabolism ; }, abstract = {Although the U.S. Environmental Protection Agency has restricted the industrial use of regulated forms of asbestos in the United States since the early 1970s, environmental exposure to asbestos remains a health concern in the United States and is a significant health issue among developing countries. Exposure to asbestos is associated with chronic pulmonary diseases and cancer of the lung, pleura, and peritoneum. The mechanism of fiber carcinogenesis is far from clear and is likely to be complex, depending on fiber dimensions, surface properties, and physical durability. The induction of reactive oxygen and nitrogen species upon phagocytosis of fibers plays an important role in fiber genotoxicity. The beta igH3, a secreted protein induced by the transforming growth factor-beta and essential for cell adhesion, is downregulated in asbestos-induced tumorigenic human bronchial epithelial cells. Ectopic expression of the beta igH3 gene abrogates the tumorigenic phenotype and suggests that the gene plays a causal role in fiber carcinogenesis. A better understanding of the carcinogenic mechanism of asbestos and other mineral fibers will provide useful information on interventional and preventive measures for asbestos-mediated diseases such as human pleural and peritoneal mesotheliomas.}, } @article {pmid16920666, year = {2006}, author = {Horton, K and Kapil, V and Larson, T and Muravov, O and Melnikova, N and Anderson, B}, title = {A review of the federal government's health activities in response to asbestos-contaminated ore found in Libby, Montana.}, journal = {Inhalation toxicology}, volume = {18}, number = {12}, pages = {925-940}, doi = {10.1080/08958370600835161}, pmid = {16920666}, issn = {1091-7691}, mesh = {*Aluminum Silicates/chemistry ; Asbestos/*adverse effects/analysis ; Asbestosis/etiology/mortality ; Cause of Death ; Environmental Exposure/*adverse effects ; Environmental Health/*legislation & jurisprudence ; Federal Government ; Female ; Humans ; Male ; *Mining ; Montana/epidemiology ; Mortality ; Public Health/*methods ; Public Health Administration ; State Government ; }, abstract = {Vermiculite ore is a naturally occurring fibrous mineral widely used in various consumer products, such as attic insulation, lawn and garden products, and fireproofing material. While most vermiculite ore and products do not pose a health hazard, the vermiculite mined from Libby, MT was contaminated with naturally occurring asbestos. The federal Agency for Toxic Substances and Disease Registry (ATSDR) has documented a significant number of asbestos-related deaths among Libby residents. Additionally, as part of the ongoing investigation, ATSDR has learned that this contaminated ore was shipped to hundreds of locations around the United States for processing. While the Libby mine is now closed, studies from ATSDR and elsewhere show that people who worked in the Libby mine or vermiculite processing facilities may have been exposed to hazardous levels of asbestos while the facilities were in operation. People who lived or worked near these sites also may have been exposed to asbestos if they came into contact with contaminated vermiculite. Prolonged exposure to asbestos can cause serious and life-threatening health conditions, including asbestosis, lung cancer, and mesothelioma. In response, ATSDR has initiated 10 different activities to help evaluate the potential health effects among Libby residents and populations throughout the United States who might have been exposed to the asbestos-contaminated ore found in Montana. Some of these activities include conducting environmental exposure evaluations, health statistics reviews, community screenings, and disease-specific surveillance. This article presents the various follow-up activities that have been conducted to date by ATSDR and partnering state health departments.}, } @article {pmid16919927, year = {2007}, author = {Ohar, JA and Ampleford, EJ and Howard, SE and Sterling, DA}, title = {Identification of a mesothelioma phenotype.}, journal = {Respiratory medicine}, volume = {101}, number = {3}, pages = {503-509}, doi = {10.1016/j.rmed.2006.06.028}, pmid = {16919927}, issn = {0954-6111}, mesh = {Age Factors ; Aged ; Asbestos/*adverse effects ; Educational Status ; Family Health ; Female ; Humans ; Lung Neoplasms/*genetics/mortality ; Male ; Mesothelioma/*genetics/mortality ; Middle Aged ; Neoplasms, Multiple Primary ; Occupational Diseases/*genetics/mortality ; Occupational Exposure/adverse effects ; Peritoneal Neoplasms/genetics/mortality ; Phenotype ; Pleural Neoplasms/genetics/mortality ; Risk Factors ; Sex Factors ; Smoking/adverse effects ; }, abstract = {Despite the strong association of asbestos exposure to mesothelioma, only a fraction of persons exposed develop this neoplasm which is characterized by long latency and shortened survival. Familial clustering implicates both exposure and genetic predisposition as causative, but a biologically relevant mesothelioma phenotype essential to genetic analysis has not been defined. To identify a more extensive set of traits that would define a mesothelioma phenotype for the purpose of genetic analysis, we set to determine characteristics that distinguish mesothelioma patients from others exposed to asbestos and to identify factors that predict the presence of mesothelioma over other mesenchymal tumors of the peritoneum and carcinoma metastatic to the pleura. We compared demographics in four asbestos-exposed groups (controls n=347, bronchogenic cancer n=67, mesothelioma n=179 and benign asbestos-induced lung disease (BALD) n=3757). Within the mesothelioma group, we compared traits to identify characteristics associated with shortened survival. We found that compared to other asbestos-exposed groups, subjects with mesothelioma were younger at first asbestos exposure, had a greater risk of a second cancer diagnosis (odds ratio=3.29), had a longer disease latency, and had a greater risk of cancer among first-degree relatives (point estimate for risk 2.93; 95% CI 2.5-3.5). Thoracic tumor location, work exposure and male gender were consistently associated with shortened survival (1.9+/-1.3 years). We conclude that thoracic tumor location, work exposure, male gender, long latency, early age at first exposure, presence of a second cancer, and first-degree relative with cancer define a phenotype that sets mesothelioma patients with a short survival apart from other asbestos-exposed individuals. We propose that this phenotype be applied to candidate gene analysis.}, } @article {pmid16918985, year = {2006}, author = {Morrison, J and Stamenkovic, S and Walker, WS and Wallace, WA}, title = {Pulmonary histiocytosis X in a patient with epithelioid mesothelioma.}, journal = {Histopathology}, volume = {49}, number = {3}, pages = {320-321}, doi = {10.1111/j.1365-2559.2006.02391.x}, pmid = {16918985}, issn = {0309-0167}, mesh = {Asbestos/adverse effects ; Histiocytosis, Langerhans-Cell/*complications/pathology/surgery ; Humans ; Male ; Mesothelioma/*complications/pathology/surgery ; Middle Aged ; Neoplasm Staging ; Pleural Neoplasms/*complications/pathology/surgery ; Pulmonary Emphysema/complications ; Pulmonary Surgical Procedures ; Smoking/adverse effects ; }, } @article {pmid16911785, year = {2006}, author = {Vordermark, D and Said, HM and Katzer, A and Kuhnt, T and Hänsgen, G and Dunst, J and Flentje, M and Bache, M}, title = {Plasma osteopontin levels in patients with head and neck cancer and cervix cancer are critically dependent on the choice of ELISA system.}, journal = {BMC cancer}, volume = {6}, number = {}, pages = {207}, pmid = {16911785}, issn = {1471-2407}, mesh = {Enzyme-Linked Immunosorbent Assay/*methods ; Female ; Head and Neck Neoplasms/*blood ; Humans ; Male ; Osteopontin ; Sialoglycoproteins/*blood ; Uterine Cervical Neoplasms/*blood ; }, abstract = {BACKGROUND: The tumor-associated glycoprotein osteopontin (OPN) is discussed as a plasma surrogate marker of tumor hypoxia and as an indicator of the presence of pleural mesothelioma in asbestos-exposed individuals. The clinical introduction of plasma OPN measurements requires the availability of a reliable enzyme-linked immunosorbence assay (ELISA).

METHODS: We compared previously described and currently available ELISA systems on 88 archival plasma samples obtained from patients with head and neck or cervix cancer between 20 days before and 171 after the start of radiotherapy.

RESULTS: Median (range) plasma OPN levels were 667 (148.8-2095) ng/ml and 9.8 (3.5-189.5) ng/ml for a previously described and a newly marketed assay, respectively. Although results for different assays were significantly correlated (r = 0.38, p < 0.05, Spearman rank test), between-assay factors ranged from 2.0 to 217.9 (median 74.6) in individual patients. OPN levels in cervix cancer patients were comparable to those of head and neck cancer patients.

CONCLUSION: Commercially available OPN ELISA systems produce different absolute plasma OPN levels, compromising a comparison of individual patient data with published results. However, different assays appear to have a similar capacity to rank patients according to plasma OPN level. A review of literature data suggests that plasma OPN levels measured even with identical ELISA systems can only be compared with caution.}, } @article {pmid16909142, year = {2006}, author = {Camidge, DR and Stockton, DL and Bain, M}, title = {Factors affecting the mesothelioma detection rate within national and international epidemiological studies: insights from Scottish linked cancer registry-mortality data.}, journal = {British journal of cancer}, volume = {95}, number = {5}, pages = {649-652}, pmid = {16909142}, issn = {0007-0920}, mesh = {Female ; Humans ; Male ; Mesothelioma/classification/*diagnosis/*epidemiology/mortality ; Registries ; Reproducibility of Results ; Scotland ; Sex Characteristics ; Survival Analysis ; }, abstract = {ICD-9 code 163 (malignant neoplasm of pleura) listed as underlying cause of death detected only 40% of Scottish mesothelioma cases (all body sites) from the cancer registry in 1981-1999. This is lower than both the previously published 55% figure, derived from UK mesothelioma register data 1986-1991, which is based on any mention of mesothelioma on death certificates, cross-referenced to cancer registry data, and the 44% figure derived from Scottish mortality data 1981-1999, which captured any mention of mesothelioma on the death certificate. Detection from cancer registry data increased to 75% under ICD-10 in Scotland, confirming earlier predictions of the benefit of ICD-10's more specific mesothelioma codes. Including the accidental poisoning codes E866.4 (ICD-9) and X49 (ICD-10), covering poisoning by 'unspecified' and 'other' causes, which appear to have been used as coding surrogates for mesothelioma when asbestos exposure was explicitly mentioned in deaths suggestive of a mesothelioma, and which are recorded as the underlying cause of death in 4-7% of mesotheliomas, may improve the mesothelioma detection rate in future epidemiological studies.}, } @article {pmid16903273, year = {2006}, author = {Brunner, TJ and Wick, P and Manser, P and Spohn, P and Grass, RN and Limbach, LK and Bruinink, A and Stark, WJ}, title = {In vitro cytotoxicity of oxide nanoparticles: comparison to asbestos, silica, and the effect of particle solubility.}, journal = {Environmental science & technology}, volume = {40}, number = {14}, pages = {4374-4381}, doi = {10.1021/es052069i}, pmid = {16903273}, issn = {0013-936X}, mesh = {Asbestos/chemistry/*toxicity ; Fibroblasts/drug effects ; Microscopy, Electron, Transmission ; *Nanoparticles ; Reference Standards ; Silicon Dioxide/chemistry/*toxicity ; Solubility ; }, abstract = {Early indicators for nanoparticle-derived adverse health effects should provide a relative measure for cytotoxicity of nanomaterials in comparison to existing toxicological data. We have therefore evaluated a human mesothelioma and a rodent fibroblast cell line for in vitro cytotoxicity tests using seven industrially important nanoparticles. Their response in terms of metabolic activity and cell proliferation of cultures exposed to 0-30 ppm nanoparticles (microg g(-1)) was compared to the effects of nontoxic amorphous silica and toxic crocidolite asbestos. Solubility was found to strongly influence the cytotoxic response. The results further revealed a nanoparticle-specific cytotoxic mechanism for uncoated iron oxide and partial detoxification or recovery after treatment with zirconia, ceria, or titania. While in vitro experiments may never replace in vivo studies, the relatively simple cytotoxic tests provide a readily available pre-screening method.}, } @article {pmid16889169, year = {2006}, author = {Bendayan, D and Kramer, MR}, title = {Malignant mesothelioma: A disease that continues to mystify.}, journal = {The Israel Medical Association journal : IMAJ}, volume = {8}, number = {7}, pages = {501-502}, pmid = {16889169}, issn = {1565-1088}, mesh = {Asbestos/*adverse effects ; Genetic Predisposition to Disease ; Humans ; Lung Neoplasms/*etiology/genetics/virology ; Mesothelioma/*etiology/genetics/virology ; Mineral Fibers/adverse effects ; Simian virus 40/*genetics/pathogenicity ; }, } @article {pmid16878282, year = {2006}, author = {Hatzinger, M and Häcker, A and Langbein, S and Grobholz, R and Alken, P}, title = {[Malignant mesothelioma of the testes].}, journal = {Aktuelle Urologie}, volume = {37}, number = {4}, pages = {281-283}, doi = {10.1055/s-2005-915617}, pmid = {16878282}, issn = {0001-7868}, mesh = {Aged ; Asbestos/adverse effects ; Diagnosis, Differential ; Humans ; Male ; *Mesothelioma/diagnostic imaging/etiology/pathology/surgery ; Occupational Exposure/adverse effects ; Orchiectomy ; *Testicular Neoplasms/diagnostic imaging/etiology/pathology/surgery ; Testis/pathology ; Time Factors ; Ultrasonography ; }, abstract = {INTRODUCTION: Malignant mesothelioma of the tunica vaginalis is a very rare malignant tumour. The prevalence of mesothelioma is about 1 : 1 000 000: Only 1 % have their origin in the tunica vaginalis testis with a 5-year survival of less than 5 %. About 80 cases have been reported in the literature. In 41 % of these cases exposure to asbestos for many years was determines.

CASE REPORT: We report on a 76-year-old patient who presented with an atypical hydrocele testis. Intraoperatively, thickened testicular walls and an crystalline lawn adjacent to the tunica vaginalis testis were found.

CONCLUSIONS: Ultrasonography showing snow flurries together with cloudy hydrocele fluid and visible crystal particles and thickened testicular walls may help to identify a mesothelioma of the testicular walls. Intraoperative frozen section and a high inguinal orchiectomy is the operative method of choice.}, } @article {pmid16871953, year = {2006}, author = {Szubert, Z and Stankiewicz-Choroszucha, B and Wrońska-Sobolewska, M and Siewierska, H and Kosińska, M and Borys, W and Jakubowski, J and Wróbel, R and Gazda, U and Kedzierska, B and Andrzejewski, M and Sova, M and Pawłowska-Koziełł, H and Komorowska, E and Ksiazkiewicz, B and Sobala, W and Szeszenia-Dabrowska, N}, title = {[Prophylactic examinations of workers formerly employed in asbestos processing plants: outcome of the Amiantus project in 2000-2004].}, journal = {Medycyna pracy}, volume = {57}, number = {2}, pages = {101-108}, pmid = {16871953}, issn = {0465-5893}, mesh = {Adult ; Aged ; Aged, 80 and over ; Air Pollutants, Occupational/*analysis ; Asbestosis/*diagnosis/epidemiology/prevention & control ; Databases, Factual ; Environmental Monitoring/methods/*statistics & numerical data ; Epidemiological Monitoring ; Female ; Health Plan Implementation ; Health Policy ; Humans ; Lung Neoplasms/diagnosis/epidemiology/*prevention & control ; Male ; Mass Screening/*methods/statistics & numerical data ; Middle Aged ; National Health Programs/organization & administration ; Occupational Diseases/diagnosis/epidemiology/*prevention & control ; Occupational Exposure/*statistics & numerical data ; Poland/epidemiology ; Population Surveillance ; Program Evaluation ; Public Health ; }, abstract = {BACKGROUND: Prophylactic examinations of workers formerly employed in asbestos processing plants were performed by virtue of the Act, dated 19 June 1997, putting a ban on the production of asbestos-containing products. To enforce the provisions of the Act, the Ministry of Health has initiated the Amiantus project implemented by 13 Occupational Medicine Centers throughout the country and coordinated by the Nofer Institute of Occupational Medicine (IMP) in Lódź.

MATERIAL AND METHODS: All the Centers perform diagnostic procedures according to the same criteria (clinical, radiological, spirometric and histological), based on the 1997 Helsinki criteria, to diagnose asbestos-related diseases. A specific "Examination Form", developed for the needs of the Amiantus project, is completed by an occupational physician during examinations and sent to the IMP, where health effects in the whole population covered by the project are monitored. Periodical medical examinations are performed at least every three years and they include: general examination, chest x-ray, resting spirometric examination and supplementary examinations (e.g., resting gasometric examination) or other diagnostic examinations if necessary (e.g., computed tomography).

RESULTS: Owing to the project implementation, it was possible to collect in the database information on 5466 persons who underwent 8763 prophylactic examinations in 2000-2004. Of the total population examined during a five-year period, occupational disease was certified in 728 (13%) persons. Asbestosis was diagnosed in 790 persons, lung cancer in 19 persons and pleural mesothelioma in 12 persons. Pleural changes in x-ray imaging were found in 1662 (30%) persons and opacities in pulmonary parenchyma in 2088 (38%) persons. Having compared these results with those from previous examinations, the total health condition deterioration was observed in 882 (16%) persons, including worsening of the lung x-ray imaging in 512 (9%) persons. An analysis showed the highest incidence of asbestos-related pathologies in workers of asbestos-cement plants. The collected data also confirmed an upward trend in the incidence of asbestosis and changes in the lung x-ray imaging related to age, duration of employment and latency.

CONCLUSION: The implementation of the Amiantus project has contributed to an increased detection of pathologies related with exposure to asbestos fibers. A growing proportion of radiograms, which indicate worsening of health condition provides evidence that morbid processes in the respiratory system are progressing in persons who in the past were occupationally exposed to asbestos dust.}, } @article {pmid16864558, year = {2006}, author = {Dodson, RF and Hammar, SP}, title = {Pleural mesothelioma in a woman whose documented past exposure to asbestos was from smoking asbestos-containing filtered cigarettes: the comparative value of analytical transmission electron microscopic analysis of lung and lymph-node tissue.}, journal = {Inhalation toxicology}, volume = {18}, number = {9}, pages = {679-684}, doi = {10.1080/08958370600743068}, pmid = {16864558}, issn = {1091-7691}, mesh = {Aged ; Asbestos, Crocidolite/*adverse effects/analysis ; Body Burden ; Fatal Outcome ; Female ; Humans ; Lung/chemistry/drug effects/*ultrastructure ; Lymph Nodes/chemistry/drug effects/*ultrastructure ; Mesothelioma/chemistry/etiology/*pathology ; Microscopy, Energy-Filtering Transmission Electron/*methods ; Pleural Neoplasms/chemistry/etiology/*pathology ; Smoking/*adverse effects ; }, abstract = {Asbestos has had many commercial applications, including its use as a major component in various types of filters. Between 1952 and 1956, crocidolite asbestos was used as a component of filters for cigarettes, reportedly greatly reducing tars and nicotine from mainstream smoke. This case report quantifies asbestos burden in lung and lymph node tissue in a 67-yr-old woman who succumbed to mesothelioma. Her only historically documented exposure to asbestos was from smoking crocidolite asbestos-containing filtered cigarettes between 1952 and 1956. Tissue digestion analysis by analytical transmission electron microscopy (ATEM) identified crocidolite fibers in lungs and thoracic lymph nodes. Combined ATEM data of lung and lymph node tissue clarified the patient's exposure to asbestos and particularly to crocidolite asbestos and thus to the presence of an entity recognized as the causal agent for mesothelioma.}, } @article {pmid16850164, year = {2006}, author = {Miura, Y and Nishimura, Y and Katsuyama, H and Maeda, M and Hayashi, H and Dong, M and Hyodoh, F and Tomita, M and Matsuo, Y and Uesaka, A and Kuribayashi, K and Nakano, T and Kishimoto, T and Otsuki, T}, title = {Involvement of IL-10 and Bcl-2 in resistance against an asbestos-induced apoptosis of T cells.}, journal = {Apoptosis : an international journal on programmed cell death}, volume = {11}, number = {10}, pages = {1825-1835}, doi = {10.1007/s10495-006-9235-4}, pmid = {16850164}, issn = {1360-8185}, mesh = {Apoptosis/*drug effects ; Apoptosis Regulatory Proteins/metabolism ; Asbestos/*adverse effects ; Asbestos, Serpentine/adverse effects/pharmacology ; Asbestosis/blood ; Cell Proliferation ; Cells, Cultured ; Cytokines/biosynthesis ; Humans ; Interleukin-10/metabolism/*physiology ; Leukocytes/pathology ; Mesothelioma/blood ; Models, Biological ; Proto-Oncogene Proteins c-bcl-2/metabolism/*physiology ; STAT3 Transcription Factor/metabolism ; T-Lymphocytes/*drug effects/metabolism ; bcl-2-Associated X Protein/metabolism ; src-Family Kinases/metabolism ; }, abstract = {To analyze the possibility that immunological alteration in asbestos-related diseases (ARDs) such as asbestosis (ASB) and malignant mesothelioma (MM) may affect the progression of cancers, a human adult T cell leukemia virus-immortalized T cell line (MT-2Org) was continuously exposed to 10 mug/ml of chrysotile-B (CB), an asbestos. After at least 8 months of exposure, the rate of apoptosis in the cells became very low and the resultant subline was designated MT-2Rst. The MT-2Rst cells were characterized by (i) enhanced expression of bcl-2, with regain of apoptosis-sensitivity by reduction of bcl-2 by siRNA, (ii) excess IL-10 secretion and expression, and (iii) activation of STAT3 that was inhibited by PP2, a specific inhibitor of Src family kinases. These results suggested that the contact between cells and asbestos may affect the human immune system and trigger a cascade of biological events such as activation of Src family kinases, enhancement of IL-10 expression, STAT3 activation and Bcl-2 overexpression. This speculation was partially confirmed by the detection of elevated bcl-2 expression levels in CD4 + peripheral blood T cells from patients with MM compared with those from patients with ASB or healthy donors. Further studies will be required to verify the role of T cells with enhanced bcl-2 expression in tumor progression induced by asbestos exposure.}, } @article {pmid16847927, year = {2006}, author = {Schure, PJ and van Dalen, KC and Ruitenberg, HM and van Dalen, T}, title = {Mesothelioma of the tunica vaginalis testis: a rare malignancy mimicking more common inguino-scrotal masses.}, journal = {Journal of surgical oncology}, volume = {94}, number = {2}, pages = {162-4; discussion 161}, doi = {10.1002/jso.20428}, pmid = {16847927}, issn = {0022-4790}, mesh = {Adult ; Diagnosis, Differential ; Humans ; Magnetic Resonance Imaging ; Male ; Mesothelioma/*diagnosis/pathology/surgery ; Middle Aged ; Orchiectomy ; Prognosis ; Testicular Hydrocele/*complications ; Testicular Neoplasms/*diagnosis/pathology/surgery ; }, abstract = {Malignant pleural mesotheliomas are rare malignancies associated with asbestos exposure and these tumors are infamous for their poor prognosis. Mesotheliomas in other body areas are much rarer. They may occur in the abdominal cavity and also in the inguinal region. In the latter area they are commonly confused with much commoner benign conditions. We present three cases of mesotheliomas in the tunica vaginalis testis.}, } @article {pmid16844568, year = {2006}, author = {Marchevsky, AM and Harber, P and Crawford, L and Wick, MR}, title = {Mesothelioma in patients with nonoccupational asbestos exposure. An evidence-based approach to causation assessment.}, journal = {Annals of diagnostic pathology}, volume = {10}, number = {4}, pages = {241-250}, doi = {10.1016/j.anndiagpath.2006.06.012}, pmid = {16844568}, issn = {1092-9134}, mesh = {Asbestos/*toxicity ; Carcinogens/*toxicity ; Environmental Exposure/*adverse effects ; Evidence-Based Medicine ; Female ; Humans ; MEDLINE ; Male ; Mesothelioma/*etiology/pathology ; Pleural Neoplasms/*etiology/pathology ; Toxicology ; }, abstract = {The specific parameters of nonoccupational asbestos exposures (NOAE) that can distinguish an idiopathic from an asbestos-caused malignant mesothelioma (MM) are controversial. A systematic literature review yielded 1028 cases with this putative association. Only 287 of those reports had a defined single exposure to a household, building occupant, or neighborhood/community asbestos source. The available "evidence" was used to develop semiarbitrary evidence-based causation guideline rules for the assessment of putative associations between MM and NOAE. The rules are classified into class A (tissue burden analysis shows asbestos body counts or fiber counts in lung tissues comparable to MM caused by occupational exposure to asbestos) and classes B to D based on whether certain combinations of NOAE features and MM (evidence) have been described in over 15% (class B), 5% to 15% (class C), and less than 5% (class D) of the patients reviewed. The proposed 4 classes of evidence-based causation guidelines provide a semiarbitrary framework to evaluate the causation of individual MM patients by NOAE based on decreasing levels of currently available evidence. The neoplasms in classes A to C patients are probably caused by NOAE, with decreasing weight of evidence in the 3 groups. There is minimal evidence to support the causation of MM by NOAE in class D patients. There is no evidence or only anecdotal evidence to support a causal association between MM and NOAE in individuals who cannot be classified into any of the 4 classes. Future studies are needed to provide more comprehensive data regarding the association between MM and NOAE.}, } @article {pmid16843042, year = {2006}, author = {Boffetta, P}, title = {Human cancer from environmental pollutants: the epidemiological evidence.}, journal = {Mutation research}, volume = {608}, number = {2}, pages = {157-162}, doi = {10.1016/j.mrgentox.2006.02.015}, pmid = {16843042}, issn = {0027-5107}, mesh = {Air Pollution, Indoor/adverse effects ; Arsenic/toxicity ; Asbestos/toxicity ; Dioxins/toxicity ; Electromagnetic Fields/adverse effects ; Environmental Pollutants/*toxicity ; Europe/epidemiology ; Humans ; Neoplasms/chemically induced/epidemiology/*etiology ; Pesticides/toxicity ; Radon/toxicity ; Risk Factors ; Tobacco Smoke Pollution/adverse effects ; Water Pollutants, Chemical/toxicity ; Water Purification ; }, abstract = {An increased risk of mesothelioma has been reported among individuals experiencing residential exposure to asbestos, while results for lung cancer are less consistent. Several studies have reported an increased risk of lung cancer risk from outdoor air pollution: on the basis of the results of the largest study, the proportion of lung cancers attributable to urban air pollution in Europe can be as high as 10.7%. A causal association has been established between second-hand tobacco smoking and lung cancer, which may be responsible for 1.6% of lung cancers. Radon is another carcinogen present in indoor air, which may be responsible for 4.5% of lung cancers. An increased risk of bladder might be due to water chlorination by-products. The available evidence on cancer risk following exposure to other environmental pollutants, including, pesticides, dioxins and electro-magnetic fields, is inconclusive.}, } @article {pmid16835500, year = {2006}, author = {Alfonso, HS and Fritschi, L and de Klerk, NH and Ambrosini, GL and Beilby, J and Olsen, N and Musk, AW}, title = {Plasma vitamin concentrations and incidence of mesothelioma and lung cancer in individuals exposed to crocidolite at Wittenoom, Western Australia.}, journal = {European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP)}, volume = {15}, number = {4}, pages = {290-294}, doi = {10.1097/00008469-200608000-00003}, pmid = {16835500}, issn = {0959-8278}, mesh = {Adult ; Aged ; Asbestos, Crocidolite/*toxicity ; Carcinogens, Environmental/toxicity ; Carotenoids/blood ; Cohort Studies ; Female ; Humans ; Incidence ; Lung Neoplasms/*chemically induced/*epidemiology ; Male ; Mesothelioma/*chemically induced/*epidemiology ; Middle Aged ; *Occupational Exposure ; Smoking/epidemiology ; Vitamin A/blood ; Vitamin E/blood ; Vitamins/*blood ; Western Australia/epidemiology ; }, abstract = {Increased rates of death from asbestos-related diseases have been reported in former workers and residents exposed to crocidolite (blue asbestos) at Wittenoom (Western Australia). The relationships between plasma concentrations of retinol, carotene and vitamin E and incidence of mesothelioma and lung cancer in a cohort of people from this town were examined. The relationships were evaluated by survival analyses using data obtained at the first visit, at each visit and with the rate of change of each vitamin during the period of follow-up. Of 1953 study participants, 65 developed mesothelioma during the follow-up, and 47 developed lung cancer. A lower incidence of mesothelioma was related to plasma concentrations of retinol at the first visit [hazard ratio (HR)=0.63, 95% confidence interval=0.41-0.99], and to measurements at each visit (HR=0.71, 95% confidence interval=0.50-1.00). Plasma carotene concentrations at the first measurement, but not during the follow-up period, were associated with lower incidence of lung cancer in men and in workers. No significant associations were found between carotene concentrations and incidence of mesothelioma. Vitamin E concentrations were not significantly associated with mesothelioma or lung cancer incidence. These findings suggest that people with chronically low plasma levels of retinol have increased risk of developing mesothelioma and lung cancer.}, } @article {pmid16820752, year = {2006}, author = {, }, title = {[The French language Society of Pneumology guidelines on the pleural mesothelioma].}, journal = {Revue des maladies respiratoires}, volume = {23}, number = {3 Suppl}, pages = {6S80-6S92}, pmid = {16820752}, issn = {0761-8425}, mesh = {Asbestos/*adverse effects ; Biopsy ; *Carcinogens ; Diagnostic Imaging ; Environmental Exposure ; Humans ; *Mesothelioma/diagnosis/etiology/therapy ; Occupational Exposure ; Patient Care Planning ; *Pleural Neoplasms/diagnosis/etiology/therapy ; Quality of Life ; Risk Factors ; Social Support ; }, } @article {pmid16814945, year = {2006}, author = {Agaimy, A and Wünsch, PH}, title = {Epithelioid and sarcomatoid malignant pleural mesothelioma in endoscopic gastric biopsies: a diagnostic pitfall.}, journal = {Pathology, research and practice}, volume = {202}, number = {8}, pages = {617-622}, doi = {10.1016/j.prp.2006.05.002}, pmid = {16814945}, issn = {0344-0338}, mesh = {Adenocarcinoma/diagnosis ; Aged ; Biopsy ; Carcinosarcoma/diagnosis ; Endoscopy, Gastrointestinal ; Epithelioid Cells/*pathology ; Fatal Outcome ; Humans ; Male ; Mesothelioma/*pathology ; Pleural Neoplasms/*pathology ; Sarcoma/*pathology ; Stomach Neoplasms/*diagnosis ; Stromal Cells/pathology ; }, abstract = {Pleural malignant mesothelioma (MM) usually presents with chest pain, pleural effusion, or cough in middle-aged and elderly individuals with a history of asbestos exposure, but may rarely present at unusual metastatic sites. The luminal gastrointestinal (GI) tract is only rarely involved in patients with wide-spread disease at autopsy. Encountering MM in endoscopic GI biopsies is an exceptionally rare event in surgical pathology practice and may therefore pose great diagnostic challenges if not considered, in particular if the clinical history is not informative or the GI symptoms are the presenting signs of the disease. To our knowledge, only three cases of epithelioid mesothelioma (EM) involving the luminal GI tract (intestine) have been reported so far, but no case of sarcomatoid MM (SM) involving the GI mucosa has been described. We herein present the first two cases of MM (one each of EM and SM) of the pleura, presenting in endoscopic gastric biopsies as small polypoid lesions and poorly healing ulcers 30 and 35 months after the initial diagnosis of pleural MM, respectively. The major differential diagnoses encompass primary or metastatic adenocarcinoma in case one and cytokeratin-positive (KIT negative!) GI stromal tumors (GISTs) and sarcomatoid carcinoma in case two, as well as other rare entities.}, } @article {pmid16814911, year = {2006}, author = {Bernstein, DM and Hoskins, JA}, title = {The health effects of chrysotile: current perspective based upon recent data.}, journal = {Regulatory toxicology and pharmacology : RTP}, volume = {45}, number = {3}, pages = {252-264}, doi = {10.1016/j.yrtph.2006.04.008}, pmid = {16814911}, issn = {0273-2300}, mesh = {Animals ; Asbestos, Amphibole/chemistry/toxicity ; Asbestos, Serpentine/*chemistry/*toxicity ; Humans ; Lung/*drug effects/pathology ; Lung Neoplasms/*chemically induced ; }, abstract = {This review substantiates kinetically and pathologically the differences between chrysotile and amphiboles. The serpentine chrysotile is a thin walled sheet silicate while the amphiboles are double-chain silicates. These different chemistries result in chrysotile clearing very rapidly from the lung (T(1/2)=0.3 to 11 days) while amphiboles are among the slowest clearing fibers known (T(1/2)=500 days to infinity). Across the range of mineral fiber solubilities chrysotile lies towards the soluble end of the scale. Chronic inhalation toxicity studies with chrysotile in animals have unfortunately been performed at very high exposure concentrations resulting in lung overload. Consequently their relevance to human exposures is extremely limited. Chrysotile following subchronic inhalation at a mean exposure of 76 fibers L>20 microm/cm(3) (3413 total fibers/cm(3)) resulted in no fibrosis (Wagner score 1.8-2.6), at any time point and no difference with controls in BrdU response or biochemical and cellular parameters. The long chrysotile fibers were observed to break apart into small particles and smaller fibers. Toxicologically, chrysotile which rapidly falls apart in the lung behaves more like non-fibrous mineral dusts while response to amphibole asbestos reflects its insoluble fibrous structure. Recent quantitative reviews of epidemiological studies of mineral fibers have determined the potency of chrysotile and amphibole asbestos for causing lung cancer and mesothelioma in relation to fiber type have also differentiated between these two minerals. The most recent analyses also concluded that it is the longer, thinner fibers that have the greatest potency as has been reported in animal inhalation toxicology studies. However, one of the major difficulties in interpreting these studies is that the original exposure estimates rarely differentiated between chrysotile and amphiboles. Not unlike some other respirable particulates, to which humans are, or have been heavily occupationally exposed, there is evidence that heavy and prolonged exposure to chrysotile can produce lung cancer. The value of the present and other similar studies is that they show that low exposures to pure chrysotile do not present a detectable risk to health. Since total dose over time decides the likelihood of disease occurrence and progression, they also suggest that the risk of an adverse outcome may be low if even any high exposures experienced were of short duration.}, } @article {pmid16806404, year = {2006}, author = {Bruni, BM and Pacella, A and MazziottiTagliani, S and Gianfagna, A and Paoletti, L}, title = {Nature and extent of the exposure to fibrous amphiboles in Biancavilla.}, journal = {The Science of the total environment}, volume = {370}, number = {1}, pages = {9-16}, doi = {10.1016/j.scitotenv.2006.05.013}, pmid = {16806404}, issn = {0048-9697}, mesh = {Asbestos, Amphibole/*analysis/chemistry ; *Environmental Monitoring ; Environmental Pollutants/*analysis ; Mineral Fibers/*analysis ; Sicily ; }, abstract = {An epidemiological and environmental study in the Biancavilla area (Sicily, Italy) was recently prompted by an impressively high incidence of malignant pleural mesothelioma. Epidemiology suggested an environmental contamination by amphibole fibres rather than risks related to a specific occupational activity. The aim of this study is to describe the diffusion of fibrous amphiboles in the area and identify their source. Fibrous amphiboles were found in the products from the local quarries, which had been used for years to build houses. After sampling all around Biancavilla, three sites were detected and they were characterized by an abundant presence of mineral fibres. Fibrous amphiboles were also recovered from building materials (mortar and plasters) and airborne particulates sampled in urban sites with high dust emissions due mainly to unpaved roads. Moreover, amphibole fibres were detected in the lung tissue of a woman who died of pleural mesothelioma. The results of this study suggest that the amphibole fibre diffusion in the Biancavilla environment lasted for many years and had been maximum during the sixties and the seventies with the uncontrolled development of the local building industry. Today, the environmental situation results to be changed following both the closing of the stone quarries and the urbanization works after 2001, above all the asphalting of dusty roads. Anyway sporadic mesothelioma cases have still to be expected in the next years.}, } @article {pmid16805449, year = {2006}, author = {Poti, S and Bellomo, RK and Di Pierri, C and L'Abbate, N}, title = {[Poliomyelitis vaccine contaminated with SV40 and prior exposure to asbestos: cognitive study in a group of car repair workers].}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {28}, number = {2}, pages = {168-169}, pmid = {16805449}, issn = {1592-7830}, mesh = {Adult ; Asbestos/*adverse effects ; Asbestosis/*etiology ; *Drug Contamination ; Humans ; *Industry ; Male ; Middle Aged ; *Motor Vehicles ; *Poliovirus Vaccines ; *Simian virus 40 ; Time Factors ; }, abstract = {Pleural and pulmonary malignancies are usually associated with previous asbestos exposure and the presence of simian virus 40 (SV40) has been detected in these neoplasms. Our study aimed to investigate the health situation among mechanics servicing buses, ex-exposed to asbestos, who received polio vaccines contaminated by SV 40. We conducted a descriptive study and so we recruited, on the basis of birth date and duration in the current job, 39 mechanics, born since 1950 until 1965, with length of service above 15 years. Of all subjects a clinical examination, a lung function test and a chest radiograph were obtained. More than 30% of sample showed pharynx and larynx clinical alterations and radiological signs of previous exposure to asbestos. We didn't find pleural or pulmonary malignancies; besides 4 doubtful neoplasms required further investigations. Although exiguity of sample, these findings provide a lack of mesothelioma and lung cancer among mechanics, previously exposed to asbestos and infected by SV40.}, } @article {pmid16798876, year = {2006}, author = {Yang, H and Bocchetta, M and Kroczynska, B and Elmishad, AG and Chen, Y and Liu, Z and Bubici, C and Mossman, BT and Pass, HI and Testa, JR and Franzoso, G and Carbone, M}, title = {TNF-alpha inhibits asbestos-induced cytotoxicity via a NF-kappaB-dependent pathway, a possible mechanism for asbestos-induced oncogenesis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {103}, number = {27}, pages = {10397-10402}, pmid = {16798876}, issn = {0027-8424}, support = {P01 CA114047/CA/NCI NIH HHS/United States ; R01 CA092657/CA/NCI NIH HHS/United States ; R01 CA106567/CA/NCI NIH HHS/United States ; }, mesh = {Asbestos/*toxicity ; Cell Transformation, Neoplastic/chemically induced/genetics/*metabolism/*pathology ; Cells, Cultured ; Chromosomes, Human/genetics ; Epithelium/drug effects ; Humans ; Metaphase ; NF-kappa B/*metabolism ; RNA Interference ; Receptors, Tumor Necrosis Factor, Type I/metabolism ; Signal Transduction/*drug effects ; Tumor Necrosis Factor-alpha/genetics/*metabolism/pharmacology ; }, abstract = {Asbestos is the main cause of human malignant mesothelioma (MM). In vivo, macrophages phagocytize asbestos and, in response, release TNF-alpha and other cytokines that contribute to carcinogenesis through unknown mechanisms. In vitro, asbestos does not induce transformation of primary human mesothelial cells (HM); instead, asbestos is very cytotoxic to HM, causing extensive cell death. This finding raised an apparent paradox: How can asbestos cause MM if HM exposed to asbestos die? We found that asbestos induced the secretion of TNF-alpha and the expression of TNF-alpha receptor I in HM. Treatment of HM with TNF-alpha significantly reduced asbestos cytotoxicity. Through numerous technical approaches, including chemical inhibitors and small interfering RNA strategies, we demonstrate that, in HM, TNF-alpha activates NF-kappaB and that NF-kappaB activation leads to HM survival and resistance to the cytotoxic effects of asbestos. Our data show a critical role for TNF-alpha and NF-kappaB signaling in mediating HM responses to asbestos. TNF-alpha signaling through NF-kappaB-dependent mechanisms increases the percent of HM that survives asbestos exposure, thus increasing the pool of asbestos-damaged HM that are susceptible to malignant transformation. Cytogenetics supported this hypothesis, showing only rare, aberrant metaphases in HM exposed to asbestos and an increased mitotic rate with fewer irregular metaphases in HM exposed to both TNF-alpha and asbestos. Our findings provide a mechanistic rationale for the paradoxical inability of asbestos to transform HM in vitro, elucidate and underscore the role of TNF-alpha in asbestos pathogenesis in humans, and identify potential molecular targets for anti-MM prevention and therapy.}, } @article {pmid16795078, year = {2006}, author = {Ramos-Nino, ME and Testa, JR and Altomare, DA and Pass, HI and Carbone, M and Bocchetta, M and Mossman, BT}, title = {Cellular and molecular parameters of mesothelioma.}, journal = {Journal of cellular biochemistry}, volume = {98}, number = {4}, pages = {723-734}, pmid = {16795078}, issn = {0730-2312}, support = {R01 CA106567-01A1/CA/NCI NIH HHS/United States ; K01 CA104159/CA/NCI NIH HHS/United States ; K01 CA104159-01/CA/NCI NIH HHS/United States ; P01 CA114047/CA/NCI NIH HHS/United States ; R01 CA045745/CA/NCI NIH HHS/United States ; R01 CA106567/CA/NCI NIH HHS/United States ; K01CA104159-01/CA/NCI NIH HHS/United States ; R01CA10656/CA/NCI NIH HHS/United States ; R01CA082657-01/CA/NCI NIH HHS/United States ; CA45745/CA/NCI NIH HHS/United States ; R01 CA045745-12/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Asbestos/*adverse effects ; Cell Transformation, Neoplastic ; *Cell Transformation, Viral ; Humans ; Mesothelioma/diagnosis/etiology/*metabolism/therapy/virology ; Peritoneal Neoplasms/diagnosis/etiology/*metabolism/therapy/virology ; Pleural Neoplasms/diagnosis/etiology/*metabolism/therapy/virology ; Polyomavirus Infections/diagnosis/*metabolism/therapy ; *Simian virus 40 ; Tumor Virus Infections/diagnosis/*metabolism/therapy ; }, abstract = {Malignant mesotheliomas (MM) are neoplasms arising from mesothelial cells that line the body cavities, most commonly the pleural and peritoneal cavities. Although traditionally recognized as associated with occupational asbestos exposures, MMs can appear in individuals with no documented exposures to asbestos fibers, and emerging data suggest that genetic susceptibility and simian virus 40 (SV40) infections also facilitate the development of MMs. Both asbestos exposure and transfection of human mesothelial cells with SV40 large and small antigens (Tag, tag) cause genetic modifications and cell signaling events, most notably the induction of cell survival pathways and activation of receptors, and other proteins that favor the growth and establishment of MMs as well as their resistance to chemotherapy. Recent advances in high-throughput technologies documenting gene and protein expression in patients and animal models of MMs can now be validated in human MM tissue arrays. These have revealed expression profiles that allow more accurate diagnosis and prognosis of MMs. More importantly, serum proteomics has revealed two new candidates (osteopontin and serum mesothelin-related protein or SMRP) potentially useful in screening individuals for MMs. These mechanistic approaches offer new hope for early detection and treatment of these devastating tumors.}, } @article {pmid16789474, year = {2004}, author = {Senyigit, A and Dalgic, A and Kavak, O and Tanrikulu, AC}, title = {Determination of environmental exposure to asbestos (tremolite) and mesothelioma risks in the southeastern region of Turkey.}, journal = {Archives of environmental health}, volume = {59}, number = {12}, pages = {658-662}, doi = {10.1080/00039890409602950}, pmid = {16789474}, issn = {0003-9896}, mesh = {Asbestos/chemistry/*toxicity ; Data Collection ; *Dust ; Environmental Exposure/adverse effects/*analysis ; Epidemiologic Studies ; Housing ; Humans ; Mesothelioma/*epidemiology/etiology ; Mining ; Occupational Exposure/adverse effects/*analysis ; Risk Assessment ; Risk Factors ; Turkey/epidemiology ; }, abstract = {In this study, the authors examined the concentrations and mineralogical analyses of asbestos, and investigated mesothelioma risk in southeastern Anatolia, Turkey. They used a gravimetric dust sampler to collect samples from 2 villages and 2 asbestos mines (1 active). Samples were then evaluated by an X-ray diffractometer and an electron microscope. The authors found high concentrations of asbestos in an active mine (4.9 fibers[f]/cm3) and at a house that was plastered with asbestos (1.24 f/cm3) and had a very active population. They found a low concentration (0.0042 f/cm3) in indoor measurements taken in Armutova village, and an even lower concentration (0.000081 f/cm3) in the inactive mine environment. Outdoor measurements included a low concentration of 0.007 f/cm3 in the village environment, and a high concentration of 1.17 f/cm3 on the mine road during the passing of a sheep herd. The people in the region are continuously exposed to asbestos during normal activities. This cumulative exposure to asbestos carries sufficient risks for mesothelioma development.}, } @article {pmid16780574, year = {2006}, author = {Putzu, MG and Bruno, C and Zona, A and Massiccio, M and Pasetto, R and Piolatto, PG and Comba, P}, title = {Fluoro-edenitic fibres in the sputum of subjects from Biancavilla (Sicily): a pilot study.}, journal = {Environmental health : a global access science source}, volume = {5}, number = {}, pages = {20}, pmid = {16780574}, issn = {1476-069X}, mesh = {Asbestos, Amphibole/adverse effects/analysis ; *Environmental Exposure ; Female ; Fluorine ; Geological Phenomena ; Geology ; Humans ; Italy ; Male ; Mesothelioma/*etiology ; Middle Aged ; Mineral Fibers/*adverse effects/*analysis ; Pleural Neoplasms/*etiology ; Sputum/chemistry ; }, abstract = {BACKGROUND: An excess of mortality for malignant neoplasms of the pleura in Biancavilla, promoted an investigation for pleural mesothelioma, disclosing 17 cases. As the absence of known sources of asbestos exposure, a local stone quarry, located near the inhabited area, used for the extraction of building materials, was investigated. Amphibolic fibres were found in the quarry and identified as fluoro-edenite "new end-member of the edenite / fluoro-edenite series" and recognized as the fluoro-edenite holotype by International Mineralogical Association--Commission on New Minerals and Mineral Names. A pilot study was performed to verify the feasibility of using spontaneous sputum as an exposure indicator for these fibres, in a context in which the use of aerosol-induced sputum technique would not be easily accepted.

METHODS: Hypothesizing a behaviour of the new fibre analogous to that of asbestos, the determination of the free fibres and the ferruginous bodies in spontaneous sputum was carried out. Phase Contrast Optical Microscope and an Environmental Scanning Electron Microscope fitted with X-ray energy dispersive analysis system (micro-analysis) were used to examine the samples. The criteria for inclusion in the study were: 1) subjects hospitalized for exacerbation of chronic obstructive pulmonary disease symptoms, 2) age > or = 45 years, 3) residence in Biancavilla for at least 30 years.

RESULTS: The preliminary findings are related to 12 subjects (7 females and 5 males). Uncoated fibres (with length > 5 microm, diameter < 3 microm, aspect ratio 3.1) and ferruginous bodies were searched. Six out of twelve subjects (4 females, 2 males) had at least one of the three samples positive for the presence of fluoro-edenite, confirmed by micro-analysis. The fibre concentration found in the sputum ranged from 0.04 to 10 fibres/g; the length from 20 to 40 microm, the diameter was < 0.5 microm. No ferruginous bodies were found in any of the samples. The four women with a positive sample were housewives. Of the two men with a positive sample, one was a farmer and the other a mason. Therefore, it may be assumed that the exposure to fluoro-edenitic fibres was mainly environmental.

CONCLUSION: The occurrence of the pleural mesothelioma cases and the presence of fluoro-edenitic fibres in spontaneous sputum, evidence the need to study the biological activity of fluoro-edenitic fibres and the implementation of epidemiological monitoring systems.}, } @article {pmid16771925, year = {2006}, author = {Heyer, CM and Theile, A and Weisser, H and Reichert, J and Horch, C and Mueller, KM and Bauer, TT}, title = {Subarachnoid-pleural fistula as a complication of malignant pleural mesothelioma.}, journal = {Respirology (Carlton, Vic.)}, volume = {11}, number = {4}, pages = {502-505}, doi = {10.1111/j.1440-1843.2006.00879.x}, pmid = {16771925}, issn = {1323-7799}, mesh = {Biomarkers/cerebrospinal fluid ; Fatal Outcome ; Fistula/*complications/diagnosis/diagnostic imaging ; Humans ; Intramolecular Oxidoreductases/cerebrospinal fluid ; Lipocalins ; Magnetic Resonance Imaging ; Male ; Mesothelioma/diagnostic imaging/*pathology ; Middle Aged ; Pleural Cavity/*diagnostic imaging/pathology ; Pleural Effusion/cerebrospinal fluid/cytology ; Pleural Neoplasms/diagnostic imaging/*pathology ; Seroma/complications/diagnosis ; *Subarachnoid Space ; Tomography, X-Ray Computed ; }, abstract = {We report a 62-year-old male patient with asbestos-related malignant pleural mesothelioma who developed recurrent pleural effusions after surgical resection of paravertebral tumour masses. Pleural effusions were drained on several occasions with the patient suffering severe headaches and vascular dysregulation. Cytological studies of the pleural fluid showed no evidence of inflammatory or malignant cells. The fluid was interpreted as seroma despite its unusual transparency until magnetic resonance imaging was suggestive of a subarachnoid-pleural fistula; its presence was confirmed when beta-trace protein--a specific marker for cerebrospinal fluid--was added to the standard laboratory testing of the pleural effusion. A subarachnoid-pleural fistula has to be included in the differential diagnosis of patients with recurrent pleural effusions after surgical debulkment of malignant pleural mesothelioma. The beta-trace protein may help to establish this diagnosis especially in cases where important therapeutic consequences may need to be drawn.}, } @article {pmid16754473, year = {2006}, author = {Roomi, MW and Ivanov, V and Kalinovsky, T and Niedzwiecki, A and Rath, M}, title = {Inhibition of malignant mesothelioma cell matrix metalloproteinase production and invasion by a novel nutrient mixture.}, journal = {Experimental lung research}, volume = {32}, number = {3-4}, pages = {69-79}, doi = {10.1080/01902140600710488}, pmid = {16754473}, issn = {0190-2148}, mesh = {Ascorbic Acid/pharmacology/therapeutic use ; Camellia sinensis ; Cell Line, Tumor ; Cell Proliferation/*drug effects ; Drug Combinations ; Electrophoresis, Polyacrylamide Gel ; Humans ; Lysine/pharmacology/therapeutic use ; Matrix Metalloproteinases/*drug effects/metabolism ; Mesothelioma/*drug therapy/pathology ; Neoplasm Invasiveness ; Plant Extracts/pharmacology/therapeutic use ; Proline/pharmacology/therapeutic use ; }, abstract = {Malignant mesothelioma (MM), an asbestos-associated cancer with no known cure, is a highly aggressive tumor causing profound morbidity and nearly universal mortality. Extracellular matrix (ECM) matrix metalloproteinases (MMPs) produced by tumor and stromal cells play a key role in tumor invasion and metastasis. Prevention of ECM degradation by MMP inhibition has been shown to be a promising therapeutic approach to inhibition of cancer development. Based on reported anticancer properties, the authors investigated the effect of a mixture (NM) containing lysine, proline, ascorbic acid, and green tea extract on MM cell line MSTO-211 H proliferation (by [MTT] [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay), MMP secretion (by gelatinase zymography), invasion (through Matrigel), and morphology (by hematoxylin and eosin [H&E] staining). MMP-2 and phorbol 12-myristate 13-acetate (PMA)-induced MMP-9 secretion were inhibited by NM in a dose-dependent fashion, with virtual total inhibition at 500 microg/ml NM. Invasion through Matrigel was inhibited at 50, 100, and 500 microg/ml by 27%, 36%, and 100%, respectively. NM was not toxic to the MM cell line, and H&E staining did not indicate any changes at and below 100 microg/ml concentration. In conclusion, NM significantly inhibited MM cell MMP secretion and invasion-both important parameters for cancer prevention, suggesting NM is an effective treatment strategy for MM.}, } @article {pmid16738897, year = {2006}, author = {Mukonoweshuro, P and Attanoos, RL and Smith, ME}, title = {Nodular glomeruloid pleuroblastoma: a biphasic pleural-based malignant tumor with immature elements.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {449}, number = {2}, pages = {253-257}, pmid = {16738897}, issn = {0945-6317}, mesh = {Aged ; Asbestos/adverse effects ; Humans ; Immunohistochemistry ; Keratins/analysis ; Male ; Occupational Exposure ; Pleural Neoplasms/chemistry/etiology/*pathology ; Pulmonary Blastoma/pathology ; }, abstract = {An unusual diffuse pleural-based tumor arising in an elderly asbestos-exposed male is presented. The tumor presented in a 72-year-old male with a 30-year history of dockyard work and likely significant asbestos exposure. Macroscopically, at post mortem, the pleural tumor diffusely encased the right lung and was composed of an admixture of neoplastic macro-, and by light microscopy, micro-nodules. Histologically, the tumor had a biphasic growth pattern with glomeruloid epithelioid elements and immature blastematous mesenchymal stroma. Immunophenotypically, the tumor had a complex pattern with epithelioid elements expressing cytokeratins, desmin, carcinoembryonic antigen (CEA), Ber EP4 and E-cadherin. The diagnostic problems and medicolegal issues surrounding the diagnosis and differentiation from malignant pleural mesothelioma and other tumors are discussed.}, } @article {pmid16736942, year = {2006}, author = {Yarborough, CM}, title = {Chrysotile as a cause of mesothelioma: an assessment based on epidemiology.}, journal = {Critical reviews in toxicology}, volume = {36}, number = {2}, pages = {165-187}, doi = {10.1080/10408440500534248}, pmid = {16736942}, issn = {1040-8444}, mesh = {Asbestos, Serpentine/*toxicity ; Humans ; Mesothelioma/*chemically induced/*epidemiology ; Risk Assessment ; }, abstract = {There has been a longstanding debate about the potential contribution of chrysotile asbestos fibers to mesothelioma risk. The failure to resolve this debate has hampered decisive risk communication in the aftermath of the collapse of the World Trade Center towers and has influenced judgments about bans on asbestos use. A firm understanding of any health risks associated with natural chrysotile fibers is crucial for regulatory policy and future risk assessments of synthesized nanomaterials. Although epidemiological studies have confirmed amphibole asbestos fibers as a cause of mesothelioma, the link with chrysotile remains unsettled. An extensive review of the epidemiological cohort studies was undertaken to evaluate the extent of the evidence related to free chrysotile fibers, with particular attention to confounding by other fiber types, job exposure concentrations, and consistency of findings. The review of 71 asbestos cohorts exposed to free asbestos fibers does not support the hypothesis that chrysotile, uncontaminated by amphibolic substances, causes mesothelioma. Today, decisions about risk of chrysotile for mesothelioma in most regulatory contexts reflect public policies, not the application of the scientific method as applied to epidemiological cohort studies.}, } @article {pmid16732558, year = {2006}, author = {Sichletidis, L and Chloros, D and Chatzidimitriou, N and Tsiotsios, I and Spyratos, D and Patakas, D}, title = {Diachronic study of pleural plaques in rural population with environmental exposure to asbestos.}, journal = {American journal of industrial medicine}, volume = {49}, number = {8}, pages = {634-641}, doi = {10.1002/ajim.20334}, pmid = {16732558}, issn = {0271-3586}, mesh = {Adult ; Aged ; Asbestos/*toxicity ; Asbestos, Amphibole/*toxicity ; Disease Progression ; Environmental Exposure/*adverse effects ; Female ; Greece/epidemiology ; Humans ; Male ; Mesothelioma/*epidemiology/etiology ; Pleura/*pathology ; Pleural Diseases/*epidemiology/etiology ; Prospective Studies ; *Rural Population ; Time Factors ; }, abstract = {BACKGROUND: The progress of pleural plaques in persons exposed to environmental asbestos in Almopia, Greece were studied prospectively.

METHODS: During a 15-year period, 198 individuals, in whom pleural plaques had been observed during the period 1988-1990 were followed. Respiratory function was initially evaluated in 23. All were inhabitants of seven villages of Northern Greece, where rocks with high concentration in asbestos fibers were used for whitewashing until 1935.

RESULTS: Out of this population, 126 survived and underwent chest X-ray in 2003 while respiratory function was retested in 18. New radiological findings were compared to previous ones using digital technology. Furthermore, the cause of death of the remaining 72 was recorded. Deterioration of X-ray findings was observed in all survivors. Not only did the surface area of previous plaques increase (8.66 +/- 12.6 cm2, mean value +/- SD) but new ones also appeared. Total lung capacity decreased from 95.6 +/- 14.8 in 1998 to 76.5 +/- 9.3% predicted in 2003. It was found that out of 72 deaths, 11 people died of malignant lung neoplasm, and 4 of mesothelioma.

CONCLUSIONS: Radiological appearance of pleural plaques and respiratory function of people previously exposed to asbestos environmental pollution worsens over the years. Prevalence of mesothelioma was found to be higher than expected.}, } @article {pmid16722201, year = {2006}, author = {Green, LC}, title = {Setting the record straight.}, journal = {International journal of occupational and environmental health}, volume = {12}, number = {2}, pages = {182; author reply 182-6}, pmid = {16722201}, issn = {1077-3525}, mesh = {Asbestos/analysis/standards/*toxicity ; Humans ; Mesothelioma/*etiology ; *Occupational Exposure/standards ; Risk Assessment ; United States ; United States Occupational Safety and Health Administration/standards ; }, } @article {pmid16722200, year = {2006}, author = {Berman, DW}, title = {Setting the record straight.}, journal = {International journal of occupational and environmental health}, volume = {12}, number = {2}, pages = {181; author reply 182-6}, pmid = {16722200}, issn = {1077-3525}, mesh = {Asbestos/analysis/standards/*toxicity ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; *Occupational Exposure/standards ; Risk Assessment ; United States ; United States Occupational Safety and Health Administration/standards ; }, } @article {pmid16722199, year = {2006}, author = {Crump, K}, title = {Setting the record straight.}, journal = {International journal of occupational and environmental health}, volume = {12}, number = {2}, pages = {180-1; author reply 182-6}, doi = {10.1179/oeh.2006.12.2.180}, pmid = {16722199}, issn = {1077-3525}, mesh = {Asbestos, Amphibole/standards/*toxicity ; Asbestos, Serpentine/standards/*toxicity ; Humans ; Mesothelioma/*etiology ; *Occupational Exposure/standards ; Risk Assessment ; United States ; United States Occupational Safety and Health Administration/standards ; }, } @article {pmid16720297, year = {2006}, author = {Fox, S and Dharmarajan, A}, title = {WNT signaling in malignant mesothelioma.}, journal = {Frontiers in bioscience : a journal and virtual library}, volume = {11}, number = {}, pages = {2106-2112}, doi = {10.2741/1953}, pmid = {16720297}, issn = {1093-9946}, mesh = {Apoptosis ; Cell Differentiation ; Disease Progression ; Epithelium/physiology ; Frizzled Receptors/*physiology ; Mesothelioma/metabolism/*physiopathology ; *Signal Transduction ; *Wnt Proteins ; beta Catenin/physiology ; }, abstract = {Neoplastic transformation of mesothelium is commonly associated with exposure to asbestos and gives rise to malignant mesothelioma, an aggressive disease that has proved particularly refractory to conventional anti-cancer therapies. The Wnt signaling pathways play key roles in fundamental processes, which include both development and homeostasis. The importance of these pathways in tumorigenesis is emphasized by the many cancers which show aberrations in Wnt signaling. In this review we examine the current evidence for activation of Wnt signaling and the abnormal expression of specific molecules in malignant mesothelioma.}, } @article {pmid16714696, year = {2006}, author = {Clarke, CP and Knight, SR and Daniel, FJ and Seevanayagam, S}, title = {Management of malignant mesothelioma by decortication and adjunct phototherapy.}, journal = {Asian cardiovascular & thoracic annals}, volume = {14}, number = {3}, pages = {206-209}, doi = {10.1177/021849230601400307}, pmid = {16714696}, issn = {1816-5370}, mesh = {Adult ; Aged ; Combined Modality Therapy ; Female ; Hematoporphyrins/therapeutic use ; Humans ; Male ; Mesothelioma/radiotherapy/surgery/*therapy ; Middle Aged ; *Phototherapy ; Pleural Neoplasms/radiotherapy/surgery/*therapy ; Treatment Outcome ; }, abstract = {Malignant mesothelioma is a relatively rare tumor that originates in the pleural space and almost invariably results from exposure to asbestos. Between September 1989 and December 1999, 100 patients were managed with curative intent using a combination of full decortication, adjunct phototherapy after administration of hematoporphyrin derivative, and strip radiotherapy to any areas where adequate clearance was not obtained. The survival curve was compared to that of 17 matched patients treated by decortication alone. Median survival increased from 250 to 440 days in the combined treatment group.}, } @article {pmid16711646, year = {2005}, author = {Petazzi, A and Gaudiello, F and Canti, Z and Mensi, C}, title = {[Cluster cases of malignant pleural mesothelioma in an oil factory].}, journal = {La Medicina del lavoro}, volume = {96}, number = {5}, pages = {440-444}, pmid = {16711646}, issn = {0025-7818}, mesh = {Aged ; Air Pollutants, Occupational/*adverse effects ; Asbestos/*adverse effects ; *Chemical Industry ; Cluster Analysis ; Humans ; Inhalation Exposure ; Italy ; Male ; Mesothelioma/*epidemiology/etiology ; Occupational Diseases/*epidemiology/etiology ; Occupational Exposure ; *Petroleum ; Pleural Neoplasms/*epidemiology/etiology ; Registries ; Sanitary Engineering/instrumentation ; Workers' Compensation/legislation & jurisprudence ; Workplace ; }, abstract = {BACKGROUND: The traditional occupational hazards of the productive cycle of oils are attributable to chemicals (use of solvents, pesticides and other agents), dusts, labour accidents (trauma, ignition, explosion), noise, manual lifting, work organization and hot-wet microclimate. The latest risk is due to the use of high temperatures (from 50 up to 250 degrees C) during the processes of extraction with solvent and refining. No cases are reported in literature of asbestos related disease in subjects who worked in oil factories. Nevertheless the structure and organization of the workplace, which is similar to that of sugar refineries, where cases of malignant mesothelioma have been described (moreover in workers employed in running and maintenance of the plants), led to the assumption that even in oil factories asbestos for the insulation of pipes and boilers could be present.

OBJECTIVES: To describe 3 cases of Malignant Mesothelioma that occurred in workers of the same oil factory.

METHODS: Since this occupational sector is not conventionally known for asbestos exposure the Local Health Unit and the Lombardy Mesothelioma Registry decided to investigate this industrial plant.

RESULTS: Following examination of the archives of the Local Health Unit and inspection of the plant, an environmental asbestos contamination (pipes and boilers) was found. The 3 cases were defined as occupational disease and the required legal procedures were initiated. This underlines the importance of close cooperation with Local Health Units of occupational medicine and the Regional Mesothelioma Registry in the study and acknowledgment of cases which would otherwise not have been recognized, with consequent loss of precious information.}, } @article {pmid16711644, year = {2005}, author = {Lombardi, S and Girelli, R and Barbieri, PG}, title = {[Two cases of pleural mesothelioma following unusual and unrecognized exposure to asbestos. The role of Occupational Health and Safety Service in identifying past occupational exposure].}, journal = {La Medicina del lavoro}, volume = {96}, number = {5}, pages = {426-431}, pmid = {16711644}, issn = {0025-7818}, mesh = {Adult ; Asbestos, Serpentine/*adverse effects ; Dust ; Equipment Design ; Fatal Outcome ; Forms and Records Control ; Humans ; *Inhalation Exposure ; Male ; Mesothelioma/*etiology ; Middle Aged ; Occupational Diseases/*etiology ; *Occupational Exposure ; Occupational Health Services/*organization & administration ; Pleural Neoplasms/*etiology ; *Records ; Resins, Synthetic ; }, abstract = {BACKGROUND: In Italy there was a wide use of asbestos in various manufacturing sectors and for many different uses, some of which are still partly or completely unknown. A detailed reconstruction of the work histories of mesothelioma patients made it possible, in some cases, to identify ignored circumstances of asbestos exposure. Moreover, the identification of cluster of cases takes on special significance in suggesting a possible previous asbestos exposure, where the information collected on single cases do not imply as much.

OBJECTIVES: This report concerns two cases of malignant mesothelioma that occurred in two workers employed in the same processes in a small factory that manufactured and repaired electric motors for hand tools.

METHODS AND RESULTS: In the Province of Brescia (one million inhabitants) a Mesothelioma Register is in operation. The first case was classified, according to Re.Na.M.1996 criteria (National Mesothelioma Register) as "unknown" occupational exposure. The identification of a second case, that was discovered thanks to the surveillance system of the Mesothelioma Register, encouraged the local Occupational Health and Safety Service to perform a more detailed investigation that revealed, for both subjects, previously unknown occupational exposure. This consisted of grinding, in a damp setting, electric motor parts bushed with phenolic thermosetting resins reinforced with chrysotile asbestos. Moreover, weekly cleaning of the plants could have been an occasion for dust dispersion. It is likely that this exposure did not last long and was limited in extent. Other similar reports of such circumstances of occupational exposure were not available in the literature.

CONCLUSIONS: The results confirm the high information value of systematic collection of incidental cases in the population, which is feasible thanks to the disease register, and the significant role of the local Occupational Health Services in demonstrating past asbestos exposure.}, } @article {pmid16707428, year = {2006}, author = {Dogan, AU and Baris, YI and Dogan, M and Emri, S and Steele, I and Elmishad, AG and Carbone, M}, title = {Genetic predisposition to fiber carcinogenesis causes a mesothelioma epidemic in Turkey.}, journal = {Cancer research}, volume = {66}, number = {10}, pages = {5063-5068}, doi = {10.1158/0008-5472.CAN-05-4642}, pmid = {16707428}, issn = {0008-5472}, support = {1PO1CA114047/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Cocarcinogenesis ; Disease Outbreaks ; Environmental Exposure ; Female ; Genetic Predisposition to Disease ; Humans ; Male ; Mesothelioma/epidemiology/*etiology/*genetics ; Middle Aged ; Models, Molecular ; Pedigree ; Turkey/epidemiology ; Zeolites/chemistry/*poisoning ; }, abstract = {Malignant mesothelioma in the western world is often associated with asbestos exposure. It is a relatively rare cancer that causes approximately 2,500 deaths yearly in the United States and 1,000 deaths yearly in the United Kingdom. In contrast, among people born in the Cappadocian (Turkey) villages of Tuzkoy, Karain, and "Old" Sarihidir, approximately 50% of deaths are caused by malignant mesothelioma. This epidemic has been attributed to erionite exposure, a type of fibrous zeolite mineral commonly found in this area of Turkey. In these three villages, malignant mesothelioma occurs in certain houses but not in others. The hypothesis was that a unique and more carcinogenic erionite was present in certain houses and caused malignant mesothelioma. We determined the X-ray diffraction pattern and the crystal structure of erionite from malignant mesothelioma villages and compared the results with the erionite samples from nearby non-malignant mesothelioma villages and from the United States. We found the same type of erionite in Cappadocian villages, with or without a malignant mesothelioma epidemic, in households with high or no incidence of malignant mesothelioma and in the United States. Pedigree studies of the three malignant mesothelioma villages showed that malignant mesothelioma was prevalent in certain families but not in others. When high-risk malignant mesothelioma family members married into families with no history of it, malignant mesothelioma appeared in the descendants. Genetically predisposed family members born and raised outside the malignant mesothelioma villages did not seem to develop malignant mesothelioma. In summary, pedigree and mineralogical studies indicate that the malignant mesothelioma epidemic is caused by erionite exposure in genetically predisposed individuals. This is the first time that genetics is shown to influence mineral fiber carcinogenesis.}, } @article {pmid16698808, year = {2006}, author = {Gun, RT and Pratt, N and Ryan, P and Roder, D}, title = {Update of mortality and cancer incidence in the Australian petroleum industry cohort.}, journal = {Occupational and environmental medicine}, volume = {63}, number = {7}, pages = {476-481}, pmid = {16698808}, issn = {1470-7926}, mesh = {Australia/epidemiology ; Cause of Death ; Cohort Studies ; Extraction and Processing Industry/*statistics & numerical data ; Female ; Humans ; Incidence ; Male ; Neoplasms/chemically induced/*mortality ; Occupational Diseases/*chemically induced ; Petroleum/*toxicity ; }, abstract = {OBJECTIVES: To update the analysis of the cohort mortality and cancer incidence study of employees in the Australian petroleum industry.

METHODS: Employees of Australian Institute of Petroleum member companies were enrolled in the cohort in four industry-wide surveys between 1981 and 1999. Mortality of 16,547 males and 1356 females was determined up to 31 December 2001 and cancer incidence to 31 December 2000. Cause specific mortality and cancer incidence were compared with those of the Australian population by means of standardised mortality ratios (SMRs) and standardised incidence ratios (SIRs). Associations between increased incidence of specific cancers and employment in the petroleum industry were tested by trends according to period of first employment, duration of employment, latency, and hydrocarbon exposure, adjusting for personal smoking history where appropriate.

RESULTS: There was a significant elevation of the incidence of mesothelioma (SIR 1.77, 95% CI 1.05 to 2.79), melanoma (SIR 1.37, 95% CI 1.19 to 1.58), and prostate cancer (SIR 1.18, 95% CI 1.04 to 1.34). The SIRs of all leukaemias and of acute non-lymphocytic leukaemia (ANLL) were not significantly different from unity, but all 11 ANLL cases were clustered in the middle to high hydrocarbon exposure categories. Tanker drivers had a significantly elevated incidence of kidney cancer (12 cases v 5.84 expected, SIR 2.05, 95% CI 1.06 to 3.59). Lung cancer incidence was significantly reduced (SIR 0.69, 95% CI 0.57 to 0.83)

CONCLUSIONS: Most cases of mesothelioma are probably related to past exposure to asbestos in refineries. No occupational cause has been identified for the excess of melanoma, or prostatic or bladder cancer. The possibility of a causal relationship between cancer of the kidney and hydrocarbon exposure warrants further study. It is uncertain whether benzene exposures, particularly past levels of exposure, have been high enough to cause ANLL.}, } @article {pmid16697254, year = {2006}, author = {Neri, M and Taioli, E and Filiberti, R and Paolo Ivaldi, G and Aldo Canessa, P and Verna, A and Marroni, P and Puntoni, R and Hirvonen, A and Garte, S}, title = {Metabolic genotypes as modulators of asbestos-related pleural malignant mesothelioma risk: a comparison of Finnish and Italian populations.}, journal = {International journal of hygiene and environmental health}, volume = {209}, number = {4}, pages = {393-398}, doi = {10.1016/j.ijheh.2006.03.002}, pmid = {16697254}, issn = {1438-4639}, mesh = {Arylamine N-Acetyltransferase/genetics ; Asbestos/*toxicity ; Case-Control Studies ; Epoxide Hydrolases/genetics ; Finland ; *Genetic Predisposition to Disease ; Genotype ; Glutathione Transferase/genetics ; Humans ; Italy ; Mesothelioma/chemically induced/epidemiology/*genetics ; Occupational Exposure/adverse effects ; Odds Ratio ; Pleural Neoplasms/chemically induced/epidemiology/*genetics ; }, abstract = {The role of CYP1A1, GSTM1, GSTT1, EPHX1, and NAT2 genotypes in susceptibility to malignant mesothelioma (MM) was compared in two case-control studies, previously conducted in two countries where different types of asbestos fibers have been used [Hirvonen et al., 1995. Inherited GSTM1 and NAT2 defects as concurrent risk modifiers in asbestos-related human malignant mesothelioma. Cancer Res. 55, 2981-2983; Hirvonen et al., 1996. Glutathione S-Transferase and N-Acetyltransferase genotypes and asbestos-associated pulmonary disorders. J. Natl. Cancer Inst.88, 1853-1856; Neri et al., 2005. Pleural malignant mesothelioma, genetic susceptibility and asbestos exposure. Mutat. Res. 592, 36-44]. Fifty-seven asbestos-exposed MM patients and 255 controls were recruited in Italy, 48 cases and 121 controls in Finland. In order to make the two studies comparable, they have been updated and new genotyping analyses have been performed. The NAT2 fast acetylator and EPHX1 low-activity genotypes were positively associated with MM in the Italian study, while they were negatively associated with this malignancy in the Finnish one. A combined significant effect was also observed in the Italian study for the NAT2 fast acetylator and EPHX1 low-activity genotypes, while this combination was protective in the Finnish study. Combination of NAT2 fast acetylator and GSTM1 null genotype posed a significantly increased risk of MM in the Italian, but not in the Finnish study. The opposite results obtained in Finland and Italy may be ascribed to random chance, but a role may be hypothesized for the fact that different types of asbestos have been used in the two countries.}, } @article {pmid16683892, year = {2006}, author = {Allen, TC and Moran, C}, title = {Synchronous pulmonary carcinoma and pleural diffuse malignant mesothelioma.}, journal = {Archives of pathology & laboratory medicine}, volume = {130}, number = {5}, pages = {721-724}, doi = {10.5858/2006-130-721-SPCAPD}, pmid = {16683892}, issn = {1543-2165}, mesh = {Adenocarcinoma, Bronchiolo-Alveolar/chemistry/*pathology/surgery ; Aged ; Biomarkers, Tumor/analysis ; Fatal Outcome ; Humans ; Immunohistochemistry ; Lung Neoplasms/chemistry/*pathology/surgery ; Male ; Mesothelioma/chemistry/*pathology/surgery ; Middle Aged ; *Neoplasms, Multiple Primary ; Pleural Neoplasms/chemistry/*pathology/surgery ; Retrospective Studies ; }, abstract = {Synchronous pulmonary carcinoma and pleural diffuse malignant mesothelioma is rare. Cases from the archives of 2 large referral centers were reviewed to identify cases of synchronously occurring pulmonary carcinoma and pleural diffuse malignant mesothelioma. Three cases of synchronous pulmonary carcinoma and pleural diffuse malignant mesothelioma were identified from more than 16,000 pleuropulmonary cases and were reviewed for demographic, clinical, radiographic, histologic, and immunohistochemical findings. The patients were men who were 63, 67, and 77 years old. Two had positive smoking histories; the smoking history of the other patient is unknown. One patient had a positive history of asbestos exposure; one patient had no history of asbestos exposure; and one patient's history of asbestos exposure is unknown. The patients underwent surgery for treatment of adenocarcinoma that was diagnosed preoperatively. Two of the adenocarcinomas were of a predominantly bronchioloalveolar pattern. No diffuse malignant mesothelioma was identified preoperatively. Diffuse malignant mesothelioma was suspected on the basis of pleural involvement by tumor with histology differing from that of the adenocarcinoma. Tumor immunostaining supported the diagnoses. The average survival after diagnosis was 6 weeks or less. In summary, the paucity of cases at 2 large referral centers and the paucity of cases reported in the English language literature highlights the rarity of synchronous pulmonary carcinoma and pleural diffuse malignant mesothelioma. These synchronous neoplasms occur in patients who have risk factors for both neoplasms independently. Length of survival following diagnosis is bleak.}, } @article {pmid16669164, year = {2005}, author = {Parducci, DA and Puccetti, M and Bianchi Martini, L and Roselli, MG and Vaghetti, E and Settimi, L and Orsi, D and Battista, G}, title = {[Mortality among workers in a cigarette factory in Lucca (Tuscany)].}, journal = {Epidemiologia e prevenzione}, volume = {29}, number = {5-6}, pages = {271-277}, pmid = {16669164}, issn = {1120-9763}, mesh = {Adolescent ; Adult ; Asbestos/*adverse effects ; Cause of Death ; Cohort Studies ; Female ; Follow-Up Studies ; Humans ; Italy ; Male ; Mesothelioma/*etiology/mortality ; Middle Aged ; Occupational Diseases/*etiology/*mortality ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*etiology/mortality ; Risk Factors ; Sex Factors ; Time Factors ; *Tobacco Industry ; }, abstract = {Aim of the present cohort study was to evaluate the mortality pattern among workers in a cigar and cigarette factory in Lucca, Italy. The study followed 2341 workers (1585 women and 756 men) registered in the company payrolls and employed for at least six months from 1 January 1960 through 1 January 1994. Follow-up was between the start of employment in the factory and 1 June 2002 (totally 74363,5 person-years). For both sexes, all-causes mortality was lower than expected (men: SMR= 0.8; CI95% 0.7-0.9; 158 deaths; women: SMR= 0.9; CI95% 0.8-1.0; 584 deaths) and no excess of mortality was reported for all malignant neoplasms. Among female workers, the frequency of deaths from pleural cancer was elevated at a statistically significant level (SMR= 6.0; CI95% 2.4-12.6; 5 deaths). One death for pleural cancer also occurred among men versus 0.4 expected. All women deceased from pleural cancer had been working in tobacco manufacturing for at least 30 years. The excess of pleural neoplasms reported in this study suggests the opportunity to evaluate the risk due to asbestos use in many manifacturing industries, especially where steam was used for extractive or warming purpose.}, } @article {pmid16649249, year = {2006}, author = {Kroczynska, B and Carbone, M}, title = {Cross reactivity between many anti-human antibodies for their hamster homologs provide the tools to study the signal transduction pathway activated by asbestos and SV40 in the malignant mesothelioma model.}, journal = {Molecular carcinogenesis}, volume = {45}, number = {7}, pages = {537-542}, doi = {10.1002/mc.20200}, pmid = {16649249}, issn = {0899-1987}, support = {R01-CA092657/CA/NCI NIH HHS/United States ; R01-CA106567/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antibodies, Monoclonal ; Antibodies, Neoplasm/*immunology ; Cell Line, Tumor ; Cells, Cultured ; Cricetinae ; Cross Reactions ; Epithelial Cells/cytology/virology ; Gene Expression Regulation, Viral ; Genome, Viral ; Humans ; Mesothelioma/genetics/*immunology/virology ; Signal Transduction/*drug effects/immunology ; Simian virus 40/genetics/*physiology ; }, abstract = {The aim of this study was to test the possibility of using human antibodies to study the pathogenic mechanism of SV40 and asbestos in a hamster mesothelioma model. The cellular lysates from human and hamster primary mesothelial cells were tested by Western blot analysis. All of the antibodies we tested (HGF, Notch, VEGF, Sp1, p53, PP2A, p-ERK1, p-c-jun, Fra1, Fra2, MMP1, MMP9, NFkappaB p65, IkappaB, GAPDH) cross-reacted with their hamster counterparts. These data indicate that hamster mesothelioma model and more in general hamster experimental model, can be used for functional studies because many mouse, rabbit, and goat monoclonal antibodies prepared against human antigens cross-react with their hamster counterparts.}, } @article {pmid16646264, year = {2005}, author = {Marinaccio, A and Altavista, P and Binazzi, A and Comba, P and Mastrantonio, M and Nesti, M and Pasetto, R and Scarselli, A and Uccelli, R and Pirastu, R}, title = {[Pleural cancer mortality and compensated cases of asbestosis in Sardinia Region municipalities (1980-2000)].}, journal = {Epidemiologia e prevenzione}, volume = {29}, number = {5-6 Suppl}, pages = {57-62}, pmid = {16646264}, issn = {1120-9763}, mesh = {Asbestosis/*epidemiology ; Female ; Humans ; Incidence ; Italy/epidemiology ; Male ; Pleural Neoplasms/*mortality ; Urban Population ; *Workers' Compensation ; }, abstract = {OBJECTIVE: To his study describes the geographical distribution of pleural cancer deaths and asbestosis cases from 1980 to 2000 in Sardinia Region (Italy). For both conditions regionwide registration systems have been available for a relatively long time and allow the identification of statistically significant clusters.

DESIGN: For each town we have estimated Standardized Mortality Ratios (SMRs) for pleural cancer and Standardized Incidence Ratios (SIRs) for asbestosis. Expected cases were estimated from age- and gender specific rates in Sardinia. SatScan software was used to identify clusters and to verify their statistical significance.

SETTING: Sardinia Region (Italy).

MAIN OUTCOME MEASURES: Standardized mortality and incidence rates respectively for pleural cancers and asbestosis cases and territorial clusters.

RESULTS: The most important cluster of pleural cancer was identified in the area defined by Carloforte, Calasetta, Portoscuso and Sant'Antioco municipalities (Southwestern Sardinia) with 15 observed cases (p value= 0.003). Other clusters were detected in the municipality of La Maddalena (11 observed cases against 1.91, expected p value= 0.008) and in Southern Sardinia between Cagliari and Sarroch (p value= 0.018). The town of Marrubiu is clearly the most important cluster (p value= 0. 001) with 6 asbestosis cases in the period.

CONCLUSIONS: These results indicate the urgency of the epidemiological surveillance of asbestos related diseases in Sardinia. The active search for incident cases of malignant mesothelioma in the whole Region and the analysis of modalities of asbestos exposure (according to national guidelines) is an indispensable tool for the primary prevention of occupational, environmental and domestic exposures from unknown asbestos sources of contamination.}, } @article {pmid16634210, year = {2006}, author = {M'barek, B and Kochbati, L and Ben Mansour, H and Ben Laïba, M and Maalej, M}, title = {[Occupational cancer in Tunisia].}, journal = {La Tunisie medicale}, volume = {84}, number = {1}, pages = {30-33}, pmid = {16634210}, issn = {0041-4131}, mesh = {Adult ; Carcinoma, Non-Small-Cell Lung/*etiology ; Humans ; Lung Neoplasms/*etiology ; Male ; Middle Aged ; *Occupational Exposure ; Pleural Neoplasms/*etiology ; Prospective Studies ; Risk Factors ; Tunisia ; }, abstract = {UNLABELLED: Occupational cancers are cancers due to the exposition of the worker during his daily work to a carcinogenic agent. In Tunisia. the number of declared and compensate cases is still low. The aim of this study is to asses the role of occupational agents in the development of bronchial and pleural cancers and to discuss the causes of this under-assessment.

METHODS AND MATERIAL: The occupational history of 107 patients with bronchial and pleural cancer was prospectively collected between Jun 2001 and July 2002. A detailed list of the possible occupational activities that would expose the worker to a carcinogenic agent incriminated in the genesis of bronchial or pleural carcinoma was used.

RESULTS: Seven cases among 107 bronchial and pleural cancers were thought to have a occupational origin (6.5%). Two patients had pleural mesothelioma due to an exposition to asbestos in the field of navy constructions and building. The 5 remaining patients had bronchial carcinomas of different histological types (3 squamous cell carcinoma, 1 adenocarcinoma and 1 small cell carcinoma). The suspected agents were Arsenic in 4/5 cases in fields of metallurgy (2 cases), mine digging (1 cases), agriculture (1 case). In 1/5 case the suspected agent was asbestos in brake- plates' maintenance in big engines. The mean duration of the exposition was 22 years and the latency period was 26 years.

CONCLUSION: The role of occupational agents in the development of bronchial and pleural cancer is important but not routinely assessed.}, } @article {pmid16632152, year = {2006}, author = {Okten, F and Köksal, D and Onal, M and Ozcan, A and Simşek, C and Ertürk, H}, title = {Computed tomography findings in 66 patients with malignant pleural mesothelioma due to environmental exposure to asbestos.}, journal = {Clinical imaging}, volume = {30}, number = {3}, pages = {177-180}, doi = {10.1016/j.clinimag.2005.12.027}, pmid = {16632152}, issn = {0899-7071}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Carcinogens ; Contrast Media/administration & dosage ; Diagnosis, Differential ; Environmental Exposure/*adverse effects ; Female ; Humans ; Male ; Mediastinum/diagnostic imaging ; Mesothelioma/*diagnosis/*etiology ; Middle Aged ; Pleura/diagnostic imaging ; Pleural Effusion, Malignant/diagnosis/etiology ; Pleural Neoplasms/*diagnosis/*etiology ; Radiographic Image Enhancement/methods ; Retrospective Studies ; Tomography, X-Ray Computed/*methods ; }, abstract = {We aimed to investigate the computed tomography (CT) findings of malignant pleural mesothelioma (MPM) caused by environmental asbestos exposure. We retrospectively reviewed CT scans of 66 patients, which were performed before any invasive procedure was done. Pleural effusion (80.3%), pleural thickening (77.2%), volume contraction (37.9%), involvement of mediastinal pleura (31.8%) and interlobar fissure (28.8%) were the most common CT findings of MPM. Although none of these findings are pathognomonic for MPM, they may provide valuable clues for the differential diagnosis, at least in patients with a history of asbestos exposure.}, } @article {pmid16630136, year = {2006}, author = {Usami, N and Fukui, T and Kondo, M and Taniguchi, T and Yokoyama, T and Mori, S and Yokoi, K and Horio, Y and Shimokata, K and Sekido, Y and Hida, T}, title = {Establishment and characterization of four malignant pleural mesothelioma cell lines from Japanese patients.}, journal = {Cancer science}, volume = {97}, number = {5}, pages = {387-394}, pmid = {16630136}, issn = {1347-9032}, mesh = {Adenocarcinoma/genetics/metabolism/pathology ; Aged ; Animals ; Cell Adhesion ; *Cell Line, Tumor ; Cell Transformation, Neoplastic/metabolism/pathology ; Cyclin-Dependent Kinase Inhibitor p16/genetics/metabolism ; DNA Mutational Analysis ; Female ; Genes, Neurofibromatosis 2 ; Humans ; Japan ; Male ; Mesothelioma/genetics/metabolism/*pathology ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Middle Aged ; Oligonucleotide Array Sequence Analysis ; Pleural Neoplasms/genetics/metabolism/*pathology ; Point Mutation ; Tumor Suppressor Protein p14ARF/genetics/metabolism ; }, abstract = {Malignant pleural mesothelioma (MPM) is an asbestos-related malignancy that is highly resistant to current therapeutic modalities. We established four MPM cell lines (ACC-MESO-1, ACC-MESO-4, Y-MESO-8A and Y-MESO-8D) from Japanese patients, with the latter two from the same patient with biphasic-like characteristics of MPM, showing epithelial and sarcomatous phenotypes, respectively, in cell culture. These cells grew well in RPMI-1640 medium supplemented with 10% fetal bovine serum under 5% CO2. Mutation and expression analyses demonstrated that the tumor suppressor gene NF2, which is known to be one of the most frequently mutated in MPM, is mutated in ACC-MESO-1. We detected homozygous deletion of p16INK4A/p14ARF in all four MPM cell lines. However, mutations of other tumor suppressor genes, including TP53, and protooncogenes, including KRAS, NRAS, BRAF, EGFR and HER2, were not found in these cell lines. Polymerase chain reaction amplification of the simian virus 40 sequence did not detect any products. We also analyzed genetic alterations of six other MPM cell lines and confirmed frequent mutations of NF2 and p16INK4A/p14ARF. To characterize the biological differences between Y-MESO-8A and Y-MESO-8D, we carried out cDNA microarray analysis and detected genes that were differentially expressed in these two cell lines. Thus, our new MPM cell lines seem to be useful as new models for studying various aspects of the biology of human MPM as well as materials for the development of future therapies.}, } @article {pmid16617847, year = {2005}, author = {Wilczyńska, U and Szymczak, W and Szeszenia-Dabrowska, N}, title = {Mortality from malignant neoplasms among workers of an asbestos processing plant in Poland: results of prolonged observation.}, journal = {International journal of occupational medicine and environmental health}, volume = {18}, number = {4}, pages = {313-326}, pmid = {16617847}, issn = {1232-1087}, mesh = {Adult ; Air Pollutants, Occupational ; Asbestos/*adverse effects ; Cohort Studies ; Female ; Humans ; Male ; Mesothelioma/etiology/*mortality ; Poland/epidemiology ; }, abstract = {OBJECTIVES: The study on mortality from cancer among workers of an asbestos plant manufacturing asbestos yarn, cloth, cords, packings, stuffing, brake linings and asbestos-rubber sheets was launched in the 1980s. The present paper discusses the results of further tracing of asbestos workers of the same plant.

MATERIALS AND METHODS: The study cohort covered 4497 workers employed at the asbestos plant in 1945-1980. The follow-up of the cohort continued until 31 December 1999. Deaths by causes were analyzed using standardized mortality ratio (SMR) calculated by the person-years method. The mortality pattern of the general population of Poland was used as reference.

RESULTS: The availability of the cohort was 93.1% (2805 men and 1382 women were traced). Mortality from malignant neoplasms in total (281 deaths among men, SMR = 118, 95%CI: 105-133 and 135 deaths among women, SMR = 159, 95%CI: 133-188) as well as that from lung cancer (102 deaths among men, SMR = 126, 95%CI: 103-153 and 18 deaths among women, SMR = 259, 95%CI: 153-409) were significantly higher than in the general population. Unlike earlier stages of analysis, the present study revealed an increased risk of pleural mesothelioma (2 deaths among men, SMR = 510, 95%CI: 62-1842 and 3 deaths among women, SMR = 2033, 95%CI: 419-5941). Mortality analysis among workers with asbestosis and in those without diagnosed asbestosis, did not reveal direct association between the risk of asbestos-induced lung cancer and previously diagnosed asbestosis.

CONCLUSIONS: The prolonged cohort tracing showed an increased risk of asbestos-related cancers. It concerned mainly workers hired by the plant between 1945-1955, when the working condition were most strenuous.}, } @article {pmid16612836, year = {2007}, author = {Nam, JM}, title = {Comparison of validity of assessment methods using indices of adjusted agreement.}, journal = {Statistics in medicine}, volume = {26}, number = {3}, pages = {620-632}, doi = {10.1002/sim.2562}, pmid = {16612836}, issn = {0277-6715}, support = {//Intramural NIH HHS/United States ; }, mesh = {Asbestos/poisoning ; Case-Control Studies ; *Data Interpretation, Statistical ; Humans ; Mesothelioma/chemically induced ; Occupational Exposure/adverse effects ; Reproducibility of Results ; Risk Assessment/*methods/standards ; }, abstract = {For comparing the validity of rating methods, the adjusted kappa (S coefficient) and Yule's Y index are better than Cohen's kappa which is affected by marginal probabilities. We consider a validity study in which a subject is assessed as exposed or not-exposed by two competing rating methods and the gold standard. We are interested in one of the methods, which is closer in agreement with the gold standard. We present statistical methods taking correlations into account for comparing the validity of the rating methods using S coefficient and Y index. We show how the S coefficient and Yule's Y index are related to sensitivity and specificity. In comparing the two rating methods, the preference is clear when the inference is the same for both S and Y. If the inference using S differs from that using Y, then it is not obvious how to decide a preference. This may occur when one rating method is better than the other in sensitivity but not in specificity. Numerical examples for comparing asbestos-exposure assessment methods are illustrated.}, } @article {pmid16584879, year = {2006}, author = {Yetkin, O}, title = {Malignant pleural mesothelioma: occupational and environmental exposure.}, journal = {Respiratory medicine}, volume = {100}, number = {6}, pages = {1121-2; author reply 1123-4}, doi = {10.1016/j.rmed.2006.02.013}, pmid = {16584879}, issn = {0954-6111}, mesh = {Asbestos/*adverse effects ; *Environmental Exposure ; Female ; Humans ; Male ; Mesothelioma/*etiology ; Occupational Exposure ; Pleural Neoplasms/*etiology ; Sex Ratio ; Turkey ; }, } @article {pmid16569690, year = {2006}, author = {Scattone, A and Pennella, A and Gentile, M and Musti, M and Nazzaro, P and Buonadonna, AL and Marzullo, A and Cavone, D and Pollice, L and Serio, G}, title = {Comparative genomic hybridisation in malignant deciduoid mesothelioma.}, journal = {Journal of clinical pathology}, volume = {59}, number = {7}, pages = {764-769}, pmid = {16569690}, issn = {0021-9746}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; *Chromosome Aberrations ; Female ; Humans ; Image Processing, Computer-Assisted ; Immunoenzyme Techniques ; Male ; Mesothelioma/etiology/*genetics/pathology ; Middle Aged ; Nucleic Acid Hybridization/methods ; Occupational Diseases/etiology/genetics/pathology ; Pleural Neoplasms/etiology/*genetics/pathology ; Prognosis ; Retrospective Studies ; }, abstract = {BACKGROUND: Malignant deciduoid mesothelioma is a rare variant of epithelioid mesothelioma. This tumour generally has poor prognosis, and can be asbestos related.

AIM: To identify peculiar genetic changes responsible for critical phases in pathogenesis of malignant deciduoid mesothelioma and their prognostic relevance.

METHODS: Comparative genomic hybridisation was carried out in six cases of malignant pleural deciduoid mesothelioma, four sporadic and two familial. All cases were found to be asbestos related. Four patients died during follow-up and the mean survival was 29.5 (SD 14.2, range 12-43) months.

RESULTS: Genetic abnormalities were found in all the tumour tissues, the most frequent being chromosomal gains at 1p, 12q, 17, 8q, 19 and 20 and losses at 13q, 6q and 9p. Survival was found to be longer in those patients who presented a smaller number of losses (< or =2) in the tumorous chromosomes.

CONCLUSIONS: Although numerous genetic changes are presented by deciduoid mesotheliomas, certain chromosomal regions are preferentially affected. The clinical outcome for this mesothelioma subtype is predicted by the number of losses.}, } @article {pmid16564556, year = {2006}, author = {Dianzani, I and Gibello, L and Biava, A and Giordano, M and Bertolotti, M and Betti, M and Ferrante, D and Guarrera, S and Betta, GP and Mirabelli, D and Matullo, G and Magnani, C}, title = {Polymorphisms in DNA repair genes as risk factors for asbestos-related malignant mesothelioma in a general population study.}, journal = {Mutation research}, volume = {599}, number = {1-2}, pages = {124-134}, doi = {10.1016/j.mrfmmm.2006.02.005}, pmid = {16564556}, issn = {0027-5107}, mesh = {Aged ; Asbestos/*adverse effects ; Base Sequence ; Case-Control Studies ; DNA Glycosylases/genetics ; DNA Primers/genetics ; DNA Repair/*genetics ; DNA, Neoplasm/genetics ; DNA-Binding Proteins/genetics ; Female ; Gene Frequency ; Haplotypes ; Humans ; Italy ; Male ; Mesothelioma/*etiology/*genetics ; Middle Aged ; Pleural Neoplasms/*etiology/*genetics ; *Polymorphism, Genetic ; Risk Factors ; X-ray Repair Cross Complementing Protein 1 ; Xeroderma Pigmentosum Group D Protein/genetics ; }, abstract = {Differences in response to carcinogenic agents are due to the allelic variants of the genes that control it. Key genes are those involved in the repair of the DNA damage caused by such agents. This paper describes the results of a case-control epidemiological study designed to determine the genotypes of four of these genes in persons exposed to a single genotoxic factor, i.e. asbestos, who had or had not developed malignant mesothelioma (MM). Our working hypothesis was that an imperfect DNA repair, as revealed by subtle polymorphic variants, could reduce protection against the chronic DNA insult provoked by asbestos and eventually result in mutagenesis and cancer. Seven variants (i.e. XRCC1-R399Q-NCBI SNP, XRCC1-R194W, XRCC3-T241M, XRCC3-IVS6-14, XPD-K751Q, XPD-D312N, OGG1-S326C) were investigated in 81 patients and 110 age and sex-matched controls, all residents at Casale Monferrato, a Piedmontese town highly exposed to asbestos pollution. Unconditional multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). When considered as a categorical variable, XRCC1-399Q showed an increased OR both in heterozygotes (OR=2.08; 95% CI=1.00-4.33) and homozygotes (2.38; 95% CI=0.82-6.94), although individual ORs were not significant. When it was considered as a continuous variable OR was significant (OR=1.68; 95% CI: 1.02-2.75). When genotypes were divided into "non-risk" and "risk" genotypes, i.e. those thought to be associated with increased risk in the light of the functional significance of the variants, XRCC1-399Q (Q homozygotes+Q/R heterozygotes versus R homozygotes) had an OR=2.147 (95% CI: 1.08-4.28), whereas that of XRCC3-241T (T homozygotes+M/T heterozygotes versus M homozygotes) was 4.09 (95% CI: 1.26-13.21) and that of OGG1-326C was increased, though not significantly. None of the haplotypes showed a significantly different frequency between patients and controls. This is the first report of an association between polymorphisms in DNA repair genes and asbestos-associated MM. Our data indicate that genetic factors are involved in MM development.}, } @article {pmid16556745, year = {2006}, author = {Orriols, R and Costa, R and Albanell, M and Alberti, C and Castejon, J and Monso, E and Panades, R and Rubira, N and Zock, JP and , }, title = {Reported occupational respiratory diseases in Catalonia.}, journal = {Occupational and environmental medicine}, volume = {63}, number = {4}, pages = {255-260}, pmid = {16556745}, issn = {1470-7926}, mesh = {Adult ; Confidence Intervals ; Disease Notification/standards ; Female ; Humans ; Lung Diseases/*epidemiology ; Male ; Mandatory Reporting ; Middle Aged ; Occupational Diseases/*epidemiology ; Registries/standards ; Spain/epidemiology ; }, abstract = {OBJECTIVES: A voluntary surveillance system was implemented in Catalonia (Spain) to ascertain the feasibility, incidence, and characteristics of occupational respiratory diseases and compare them with those of the compulsory official system.

METHODS: In 2002, in collaboration with the Occupational and Thoracic Societies of Catalonia, occupational and chest physicians and other specialists were invited to report, on a bimonthly basis, newly diagnosed cases of occupational respiratory diseases. Information requested on each case included diagnosis, age, sex, place of residence, occupation, suspected agent, and physician's opinion on the likelihood that the condition was work related. Compulsory official system data derived from statistics on work related diseases for possible disability benefits declared by insurance companies, which are responsible for declaring these diseases to the Autonomous Government of Catalonia.

RESULTS: Of 142 physicians seeing patients with occupational respiratory diseases approached, 102 (74%) participated. Three hundred and fifty nine cases were reported, of which asthma (48.5%), asbestos related diseases (14.5%), and acute inhalations (12.8%) were the most common. Physicians rated 63% of suspected cases as highly likely, 28% as likely, and 8% as low likelihood. The most frequent suspected agents reported for asthma were isocyanates (15.5%), persulphates (12.1%), and cleaning products (8.6%). Mesothelioma (5.9%) was the most frequent diagnosis among asbestos related diseases. The number of acute inhalations reported was high, with metal industries (26%), cleaning services (22%), and chemical industries (13%) being the most frequently involved. The frequency of occupational respiratory diseases recorded by this voluntary surveillance system was four times higher than that reported by the compulsory official system.

CONCLUSIONS: The compulsory scheme for reporting occupational lung diseases is seriously underreporting in Catalonia. A surveillance programme based on voluntary reporting by physicians may provide better understanding of the incidence and characteristics of these diseases. Persulphates and cleaning products, besides isocyanates, were the most reported causes of occupational asthma. Metal industries and cleaning services were the occupations most frequently involved in acute inhalations with a remarkably high incidence in our register.}, } @article {pmid16554677, year = {2006}, author = {Lee, JH and Lim, EJ and Lee, ES and Lee, JY and Kim, HS and Park, SY and Kim, KH and Park, JY and Lee, JY and Jang, MK and Lee, JH and Kim, HY and Yoo, JY and Nam, ES and Jo, SJ and Yun, EJ and Kim, MJ}, title = {[A case of peritoneal mesothelioma without a history of asbestos exposure].}, journal = {The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi}, volume = {47}, number = {3}, pages = {224-228}, pmid = {16554677}, issn = {1598-9992}, mesh = {Aged ; Humans ; Male ; Mesothelioma/*diagnosis/etiology/surgery ; Peritoneal Neoplasms/*diagnosis/etiology/surgery ; }, abstract = {Peritoneal mesothelioma is an unusual disease which diffusely involves the peritoneal surface. The incidence is approximately one per 1,000,000, and one fifth to one third of all mesothelioma are peritoneal in origin. Asbestos exposure is linked to the development of peritoneal mesothelioma as a significant etiology, but further investigation should be conducted. Abdominal sonography, abdominal CT and cytologic examination of ascitic fluid are used to confirm the diagnosis, but rarely provides proper diagnosis. Laparoscopy with biopsy is the most common diagnostic method for definite diagnosis of mesothelioma. Cytoreductive surgery and intraperitoneal chemotherapy have been suggested for better survival since the median survival after the initial diagnosis is near to 50 months. This report describes a case of 73-years-old male patient presented with abdominal pain and distension. This patient had not been exposed to asbestos. Abdominal sonography and CT showed massive ascites, multiple omental masses and peritoneal thickening. It was difficult to distinguish peritoneal mesothelioma from carcinomatosis. Laparoscopy and peritoneal biopsy was conducted and immunostaining examination confirmed the diagnosis of peritoneal mesothelioma.}, } @article {pmid16553258, year = {2006}, author = {García Gómez, M and Artieda Pellejero, L and Esteban Buedo, V and Guzmán Fernández, A and Camino Durán, F and Martínez Castillo, A and Lezzáun Goñi, M and Gallo Fernández, M and González García, I and Martínez Arguisuelas, N and Elvira Espinosa, M and Sánchez de Navas, AM and Zimmermann Verdejo, M and Campos Acedo, R and Galván Olivares, F and Castañeda López, R and Estaún Blasco, E and Castell Salvá, R and Martínez-Portillo, LM and Rubio Sanz, A and Unamuno Achúcarro, A and Fernández Fernández, I and Lama Herrera, C and Mayoral Cortés, JM}, title = {[Health surveillance of workers exposed to asbestos: an example of cooperation between the occupational prevention system and the national health system].}, journal = {Revista espanola de salud publica}, volume = {80}, number = {1}, pages = {27-39}, doi = {10.1590/s1135-57272006000100004}, pmid = {16553258}, issn = {1135-5727}, mesh = {Asbestosis/epidemiology/*prevention & control ; *Environmental Monitoring ; Epidemiological Monitoring ; Humans ; *Occupational Exposure ; Occupational Health Services/standards ; Population Surveillance/methods ; Preventive Health Services/standards ; Risk Management ; }, abstract = {UNLABELLED: The Ministry of Health and Consumer Affairs and the Autonomous Governments of Spain have designed and agreed by consensus with the sanitary professionals and major employer's organizations and Unions a Integral Health Surveillance Programme of asbestos-exposed workers, in order to assure appropriate, uniform and harmonized action throughout the national territory with relation to these workers.

PROGRAM DESCRIPTION: This initiative started from the Occupational Health Working group of the Interterritorial Council, with inputs from the Asbestos Working Group of the National Occupational Safety and Health Commission. It was agreed with occupational medicine and infirmary professionals and was approved by the Health and Labour authorities. The program is organised in seven main activities.

CURRENT PROGRAM STATUS: two years after the Programme approval a total of 5778 workers are included in the Registry of asbestos-exposed workers. 208 workers have COPD, 198 benign pleural disease, 8 lung cancer, 10 mesothelioma and 7 workers have other cancers possibly related to asbestos (gastric, larynx and colon cancer).

REMARKS: the agreement and participation reached in this Programme allow achieving much higher coverage of occupational prevention policies than those obtained with a mere law approval, as we could see during the second year of implementation of the Programme in which the number of attended workers has doubled.}, } @article {pmid16542214, year = {2006}, author = {Nakataki, E and Yano, S and Matsumori, Y and Goto, H and Kakiuchi, S and Muguruma, H and Bando, Y and Uehara, H and Hamada, H and Kito, K and Yokoyama, A and Sone, S}, title = {Novel orthotopic implantation model of human malignant pleural mesothelioma (EHMES-10 cells) highly expressing vascular endothelial growth factor and its receptor.}, journal = {Cancer science}, volume = {97}, number = {3}, pages = {183-191}, pmid = {16542214}, issn = {1347-9032}, mesh = {Animals ; Antineoplastic Agents/therapeutic use ; Cell Line, Tumor ; Cisplatin/therapeutic use ; Deoxycytidine/analogs & derivatives/therapeutic use ; *Disease Models, Animal ; Humans ; Immunohistochemistry ; Male ; Mesothelioma/drug therapy/*metabolism/pathology ; Mice ; Mice, SCID ; Neoplasm Transplantation ; Pleural Neoplasms/drug therapy/*metabolism/pathology ; Receptors, Vascular Endothelial Growth Factor/*biosynthesis ; Reverse Transcriptase Polymerase Chain Reaction ; Vascular Endothelial Growth Factor A/*biosynthesis ; Gemcitabine ; }, abstract = {Malignant pleural mesothelioma (MPM) is closely related to exposure to asbestos, and a rapid increase in the number of MPM patients in Japan is estimated in the years 2010-2050. The purpose of the present study was to establish a clinically relevant animal model that shows human patient-like progression of MPM. Here, we demonstrate that a human MPM cell line (EHMES-10) inoculated orthotopically (thoracic cavity) into severe combined immunodeficiency (SCID) mice produces highly vascularized thoracic tumors with pleural dissemination and bloody pleural effusions by 5 weeks, suggesting a patient-like progression of this cell line after orthotopic inoculation. EHMES-10 cells overexpressed vascular endothelial growth factor (VEGF), a molecule responsible for malignant effusions, and its receptor. Treatment with cisplatin, but not gemcitabine, significantly inhibited the production of pleural effusions, but it was not effective for thoracic tumors, consistent with chemotherapy refractory characteristics of MPM in patients. Our patient-like orthotopic model using EHMES-10 cells overexpressing VEGF and its receptor may be useful for examining the molecular pathogenesis of MPM and may contribute to the development of novel treatment strategies for MPM.}, } @article {pmid16539170, year = {2006}, author = {Vandentorren, S and Salmi, LR and Mathoulin-Pélissier, S and Baldi, I and Brochard, P and , }, title = {Imputation of individual cancer cases to occupational causes.}, journal = {Scandinavian journal of work, environment & health}, volume = {32}, number = {1}, pages = {32-40}, doi = {10.5271/sjweh.974}, pmid = {16539170}, issn = {0355-3140}, mesh = {Aged ; Air Pollutants, Occupational ; Bayes Theorem ; Expert Testimony ; Humans ; Lung Neoplasms/*etiology ; Male ; Mesothelioma/*etiology ; Middle Aged ; *Models, Biological ; Occupational Diseases/*diagnosis ; *Occupational Exposure ; }, abstract = {OBJECTIVES: Many potential occupational causes of cancer have been documented. Imputation of an individual cancer to occupational or other causes is, however, difficult. A method based on the Bayes theorem is proposed for assessing causal relationships at the individual level.

METHODS: Causality assessment, dealing with four types of persons defined by exposure and the occurrence of cancer, was linked with imputation, only dealing with persons who have cancer and were exposed. Imputation was then formulated using the Bayes theorem, relating epidemiologic information regarding causes, a patient's exposure history, and the posterior odds that the cancer was caused by a suspected occupational exposure. Data needed to apply a Bayesian method were defined in terms of relative risks, proportion of people exposed in populations, and the frequency of a positive relevant characteristic for persons without cancer. A relevant characteristic was defined using a formal consensus between experts. The method was then illustrated with cases of mesothelioma and lung cancer in possible relation to asbestos.

RESULTS: Experts defined the relevant characteristics as being qualification of occupational exposure, intensity of exposure, latency, disease characteristics, and presence of causal agent in the body. Application to mesothelioma and lung cancer cases illustrated the potential usefulness of the method.

CONCLUSIONS: The importance of occupational exposure in the formulation of imputation underscores the need for available and reliable data sources on occupational exposures. The proposed method could become a powerful tool for the expert assessment of causes of cancer cases, provided data become available in individual files and the literature.}, } @article {pmid16528669, year = {2006}, author = {Martinez, G and Loreto, C and Rapisarda, V and Masumeci, G and Valentino, M and Carnazza, ML}, title = {Effects of exposure to fluoro-edenite fibre pollution on the respiratory system: an in vivo model.}, journal = {Histology and histopathology}, volume = {21}, number = {6}, pages = {595-601}, doi = {10.14670/HH-21.595}, pmid = {16528669}, issn = {1699-5848}, mesh = {Air Pollutants/*toxicity ; Animals ; Apoptosis/drug effects ; Apoptosis Regulatory Proteins/analysis ; Asbestos, Amphibole/analysis/*toxicity ; Collagenases/analysis ; Disease Models, Animal ; Female ; Histocytochemistry ; Immunohistochemistry ; Matrix Metalloproteinase 13 ; Membrane Glycoproteins/analysis ; Mineral Fibers ; Pulmonary Alveoli/chemistry/drug effects/pathology ; Pulmonary Fibrosis/etiology/pathology ; Receptors, TNF-Related Apoptosis-Inducing Ligand ; Receptors, Tumor Necrosis Factor/analysis ; Respiratory Mucosa/chemistry/pathology ; Respiratory System/chemistry/*pathology ; Sheep ; TNF-Related Apoptosis-Inducing Ligand ; Tumor Necrosis Factor-alpha/analysis ; }, abstract = {An increased standardised rate of mortality from pleural mesothelioma among the population of Biancavilla (Sicily, Italy) has been attributed to exposure to fluoro-edenite fibres. Our aim was to establish whether and how these fibres may induce pathological effects using an in vivo model. Lung tissue collected from 60 healthy sheep selected from six flocks habitually grazing near Biancavilla and from 10 control sheep was fixed formalin and paraffin-embedded; sections were stained with haematoxylin-eosin, Masson trichrome and Gomori argentic impregnation. Histochemical studies and immunohistochemical analysis for the localisation of TRAIL, DR5 and MMP13 were also performed. The lungs of exposed sheep exhibited fibrosis and loss of alveolar architecture with honeycombing of alveolar cavities. Fluoro-edenite fibres were detected close to the alveolar epithelium and interstitia. The parenchyma showed hyaline degeneration and strong PAS-positivity in the interstitium, proteoglycan alterations, reflecting a damaged basal membrane and an involvement of the interstitial matrix. MMP-13 was overexpressed, mainly in fibroblasts and epithelial cells, while positivity for TRAIL and DR5 was detected on alveolar surfaces and in the vascular stroma. The initial pathological event seems to involve first the alveoli and subsequently the interstitium, giving rise to classic honeycombing. The triggering event at the level of type I pneumocytes would damage the cytoplasmic membrane resulting in loss of cell elements and exposure of underlying capillaries, and eventually in a series of reactions including macrophage activation, possible release of growth factors and metaplasic reconstruction of lung alveoli. Immunopositivity for TRAIL and MMP-13 receptor suggests that apoptotic processes may also be activated by fluoro-edenite.}, } @article {pmid16523977, year = {2006}, author = {Bang, KM and Pinheiro, GA and Wood, JM and Syamlal, G}, title = {Malignant mesothelioma mortality in the United States, 1999-2001.}, journal = {International journal of occupational and environmental health}, volume = {12}, number = {1}, pages = {9-15}, doi = {10.1179/oeh.2006.12.1.9}, pmid = {16523977}, issn = {1077-3525}, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Female ; Humans ; Male ; Mesothelioma/epidemiology/*etiology/*mortality ; Middle Aged ; Occupational Diseases/etiology/mortality ; Occupational Exposure/*adverse effects ; Population Surveillance ; Sex Factors ; United States/epidemiology ; }, abstract = {Malignant mesothelioma is strongly associated with asbestos exposure. This paper describes demographic, geographic, and occupational distributions of mesothelioma mortality in the United States, 1999-2001. The data (n = 7,524) were obtained from the National Center for Health Statistics multiple-cause-of-death records. Mortality rates (per million per year) were age-adjusted to the 2000 U.S. standard population, and proportionate mortality ratios (PMRs) were calculated by occupation and industry, and adjusted for age, sex, and race. The overall age-adjusted mortality rate was 11.52, with males (22.34) showing a sixfold higher rate than females (3.94). Geographic distribution of mesothelioma mortality is predominantly coastal. Occupations with significantly elevated PMRs included plumbers/pipefitters and mechanical engineers. Industries with significantly elevated PMRs included ship and boat building and repairing, and industrial and miscellaneous chemicals. These surveillance findings can be useful in generating hypotheses and developing strategies to prevent mesothelioma.}, } @article {pmid16517468, year = {2006}, author = {Roggli, VL}, title = {The role of analytical SEM in the determination of causation in malignant mesothelioma.}, journal = {Ultrastructural pathology}, volume = {30}, number = {1}, pages = {31-35}, doi = {10.1080/01913120500313192}, pmid = {16517468}, issn = {1521-0758}, mesh = {Asbestos, Amosite/adverse effects/analysis/classification ; Electron Probe Microanalysis ; Female ; Humans ; Lung/ultrastructure ; Mesothelioma/etiology/*ultrastructure ; Microscopy, Electron, Scanning/*methods ; Peritoneal Neoplasms/etiology/*ultrastructure ; Peritoneum/ultrastructure ; Pleura/ultrastructure ; Pleural Neoplasms/etiology/*ultrastructure ; }, abstract = {The causative relationship between asbestos exposure and mesothelioma is firmly established. Some information in this regard comes from analysis of the fiber content of lung tissue by means of analytical electron microscopy. The author has had the opportunity to study the lung asbestos content of 396 cases of mesothelioma, including 28 peritoneal cases, by means of analytical scanning electron microscopy. The highest fiber levels occurred in patients who also had asbestosis, which was found in 12% of pleural and 43% of peritoneal cases. Elevated tissue asbestos content was identified in 87% of pleural and 75% of peritoneal cases. Peritoneal cases that are asbestos related have on average a higher lung fiber burden than pleural cases. Mesotheliomas in women have elevated tissue asbestos content in about 60% of cases, and many of these had a history of exposure as a household contact of an asbestos worker. The main fiber type identified in our series was amphibole, predominantly amosite. These fibers have been demonstrated to reach the target tissue, the pleura.}, } @article {pmid16517467, year = {2006}, author = {Hicks, J}, title = {Biologic, cytogenetic, and molecular factors in mesothelial proliferations.}, journal = {Ultrastructural pathology}, volume = {30}, number = {1}, pages = {19-30}, doi = {10.1080/01913120500313168}, pmid = {16517467}, issn = {1521-0758}, mesh = {Asbestos/adverse effects ; Biomarkers, Tumor/analysis ; Cell Proliferation ; Cytogenetic Analysis ; Epithelium/metabolism/*pathology ; Humans ; Mesothelioma/etiology/*genetics/*pathology ; Molecular Biology ; }, abstract = {Although mesothelioma cases may have peaked in the 1990s in developed countries, it is expected that there will be over 70,000 cases diagnosed in the United States over the next 5 decades. With the industrial expansion in Southeast Asia and China and the continued use of asbestos, an epidemic of mesothelioma cases is anticipated over the next several decades. A considerable amount has been learned about the cytogenetic and molecular genetics of mesotheliomas. However, in-depth studies are needed to further define specific factors that may provide for early diagnosis, surgical treatment, oncologic management, and gene therapy. Serologic markers for surveillance of those with asbestos exposure and at risk for mesothelioma are needed. Targeted therapy using molecular markers and gene therapy may provide a means to reverse mesothelial proliferations or stabilize tumor growth and allow for surgical resection. The future holds great promise in identifying mesothelioma gene expression profiles (genomics, gene microarrays) and proteins (proteomics) that may produce the key to dealing with this dismal and devastating neoplasm.}, } @article {pmid16509294, year = {2006}, author = {Renner, R}, title = {Naturally occurring asbestos linked to cancer.}, journal = {Environmental science & technology}, volume = {40}, number = {3}, pages = {636-637}, pmid = {16509294}, issn = {0013-936X}, mesh = {Asbestos, Amphibole/*poisoning ; *Environmental Exposure ; Epidemiologic Studies ; Humans ; Mesothelioma/*etiology ; Risk Assessment ; }, } @article {pmid16500906, year = {2006}, author = {Baas, P and van 't Hullenaar, N and Wagenaar, J and Kaajan, JP and Koolen, M and Schrijver, M and Schlösser, N and Burgers, JA}, title = {Occupational asbestos exposure: how to deal with suspected mesothelioma cases--the Dutch approach.}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {17}, number = {5}, pages = {848-852}, doi = {10.1093/annonc/mdl021}, pmid = {16500906}, issn = {0923-7534}, mesh = {Aged ; Aged, 80 and over ; Air Pollutants ; Asbestos/*adverse effects ; Environmental Exposure ; Humans ; Mesothelioma/diagnosis/*etiology ; Middle Aged ; Netherlands ; Occupational Diseases/diagnosis/*etiology ; *Occupational Exposure ; Pleural Neoplasms/diagnosis/*etiology ; }, abstract = {INTRODUCTION: Patients with asbestos-related diseases, such as malignant mesothelioma (MM), are not uniformly treated in Europe when they apply for compensation. In The Netherlands, the Institute of Asbestos Victims (IAV) acts on behalf of patients with a malignant mesothelioma. In the majority of cases, the diagnosis is clear but in some, uncertainty remains. In these cases a specialist opinion of the Mesothelioma Group of the Dutch Thoracic Society (DTS) is required. The process of data handling and final outcome for these patients is discussed and compared with the situation in other European countries.

MATERIALS AND METHODS: Dutch patients with a possible malignant mesothelioma and occupational exposure to asbestos presented their cases to the IAV. In 10% of the cases, pathological confirmation of a malignant mesothelioma could not be obtained. These cases were presented to the Mesothelioma Group to obtain a clinical diagnosis based on clinical reports, occupational history, X-ray examination and other factors. Each case was reviewed by three independent pulmonologists experienced in MM. The majority view was binding for acceptance or rejection of the diagnosis.

RESULTS: In the period January 2000 until May 2005, the IAV received 1747 cases for compensation. In 161 cases no definitive diagnosis could be made on pathology and were presented to the Mesothelioma Group. Of these cases, 117 (73%) were considered to be compatible with the clinical diagnosis malignant pleural mesothelioma. Forty-four cases (27%) were rejected. In 75% of the cases (112 of 150), the conclusion of the three independent specialists was unanimous; in 11 cases one specialist refrained from a diagnosis. The median time from request to submission of the report was 34 days (range 1-185 days).

CONCLUSIONS: Compared with other European countries, this approach, as determined by the IAV and Mesothelioma Group of the DTS, is an effective and rapid way to investigate claims of patients with a possible occupationally related malignant mesothelioma.}, } @article {pmid16493164, year = {2006}, author = {Brodkin, CA and Balmes, JR and Redlich, CA and Cullen, MR}, title = {Residential proximity to naturally occurring asbestos: health risk or ecologic fallacy?.}, journal = {American journal of respiratory and critical care medicine}, volume = {173}, number = {5}, pages = {573; author reply 573-4}, doi = {10.1164/ajrccm.173.5.573}, pmid = {16493164}, issn = {1073-449X}, mesh = {Asbestos/*adverse effects ; *Carcinogens ; Environmental Exposure/*adverse effects ; Humans ; Mesothelioma/epidemiology/*etiology ; Pleural Neoplasms/epidemiology/*etiology ; *Residence Characteristics ; Risk Factors ; }, } @article {pmid16480849, year = {2006}, author = {Travaglione, S and Bruni, BM and Falzano, L and Filippini, P and Fabbri, A and Paoletti, L and Fiorentini, C}, title = {Multinucleation and pro-inflammatory cytokine release promoted by fibrous fluoro-edenite in lung epithelial A549 cells.}, journal = {Toxicology in vitro : an international journal published in association with BIBRA}, volume = {20}, number = {6}, pages = {841-850}, doi = {10.1016/j.tiv.2005.12.010}, pmid = {16480849}, issn = {0887-2333}, mesh = {Asbestos, Amphibole/*toxicity ; Asbestos, Crocidolite/toxicity ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Cells, Cultured ; Cytokines/*biosynthesis ; Epithelial Cells/drug effects ; Humans ; Inflammation/*complications ; Interleukin-6/biosynthesis ; Interleukin-8/biosynthesis ; Lung/*drug effects/pathology ; Mesothelioma/*etiology ; }, abstract = {An unusual cluster of malignant mesothelioma was evidenced in Biancavilla, a Sicily village where no inhabitant had been significantly and professionally exposed to asbestos. Mineralogical and environmental studies led to the identification of a new prismatic amphibole, named fluoro-edenite. We previously reported, by using the human lung epithelial A549 cells, that prismatic fluoro-edenite was unable to induce changes that could be somehow related to cellular transformation, and this was in accordance with studies carried out in vivo. More recently, a fibrous amphibole with a composition very similar to that of prismatic fluoro-edenite, was identified in Biancavilla. This fibrous fluoro-edenite was shown to induce mesothelioma in rats. In keeping with this effect in vivo, in the present work we observed multinucleation and spreading, common features of transformed cells, as well as pro-inflammatory cytokine release in A549 cells. Such cell changes occurred without interfering with the passage of the resulting multinucleated cells through the cell cycle and without condemning cells to death. Hence, in lung epithelial cells, fibrous fluoro-edenite behaved similarly to the unrelated asbestos type crocidolite, whose connection with severe inflammation and cancer of the lung is renowned.}, } @article {pmid16470550, year = {2006}, author = {Huuskonen, MS and Rantanen, J}, title = {Finnish Institute of Occupational Health (FIOH): prevention and detection of asbestos-related diseases, 1987-2005.}, journal = {American journal of industrial medicine}, volume = {49}, number = {3}, pages = {215-220}, doi = {10.1002/ajim.20282}, pmid = {16470550}, issn = {0271-3586}, mesh = {Asbestos/*adverse effects ; Asbestosis/epidemiology/prevention & control ; *Carcinogens ; Finland/epidemiology ; Follow-Up Studies ; Government Regulation ; Health Policy/legislation & jurisprudence ; Humans ; International Cooperation ; Lung Neoplasms/epidemiology/prevention & control ; Mesothelioma/epidemiology/prevention & control ; Occupational Diseases/epidemiology/*prevention & control ; Occupational Exposure/*prevention & control ; *Occupational Health ; Population Surveillance ; }, abstract = {BACKGROUND: Between 1987 and 1992, the Finnish Institute of Occupational Health (FIOH) initiated and implemented the Asbestos Program that aimed at reducing asbestos-related risks. It was a cooperative effort between government authorities, labor market organizations, and health care and labor protection personnel.

METHODS: During the Program and its follow-up since 1993 several preventive actions were taken, and considerable new legislation and official instructions were issued.

RESULTS: Approximately 200,000 people in Finland have been exposed to asbestos in their work. Through the cooperative efforts of government, labor, health care and worker protection programs, the import of asbestos was ceased in 1993 with a few exceptions. Almost all imports ceased in 2005 following European Union directives. Regulation of asbestos abatement companies has been greatly increased. The occupational exposure limit has been reduced from 2.0 fibers/cm(3) to the present 0.1 fibers/cm(3). Asbestos-related diseases are closely monitored and education of health care providers regarding the occupational source of these conditions is now emphasized.

CONCLUSIONS: The success of the primary goal of the Program, a reduction in asbestos-related morbidity, will not be fully realized for many decades.}, } @article {pmid16469823, year = {2006}, author = {Goldberg, M and Imbernon, E and Rolland, P and Gilg Soit Ilg, A and Savès, M and de Quillacq, A and Frenay, C and Chamming's, S and Arveux, P and Boutin, C and Launoy, G and Pairon, JC and Astoul, P and Galateau-Sallé, F and Brochard, P}, title = {The French National Mesothelioma Surveillance Program.}, journal = {Occupational and environmental medicine}, volume = {63}, number = {6}, pages = {390-395}, pmid = {16469823}, issn = {1470-7926}, mesh = {Aged ; Case-Control Studies ; Disability Evaluation ; Female ; France/epidemiology ; Humans ; Incidence ; Male ; Mesothelioma/*epidemiology/pathology ; Odds Ratio ; Pleural Neoplasms/*epidemiology/pathology ; Risk Factors ; Workers' Compensation ; }, abstract = {OBJECTIVES: The French National Mesothelioma Surveillance Program (NMSP) was established in 1998 by the National Institute for Health Surveillance (InVS). Its objectives are to estimate the trends in mesothelioma incidence and the proportion attributable to occupational asbestos exposure, to help improve its pathology diagnosis, to assess its compensation as an occupational disease, and to contribute to research.

METHODS: The NMSP records incident pleural tumours in 21 French districts that cover a population of approximately 16 million people (a quarter of the French population). A standardised procedure of pathological and clinical diagnosis ascertainment is used. Lifetime exposure to asbestos and to other factors (man made mineral fibres, ionising radiation, SV40 virus) is reconstructed, and a case-control study was also conducted. The proportion of mesothelioma compensated as an occupational disease was assessed.

RESULTS: Depending on the hypothesis, the estimated number of incident cases in 1998 ranged from 660 to 761 (women: 127 to 146; men: 533 to 615). Among men, the industries with the highest risks of mesothelioma are construction and ship repair, asbestos industry, and manufacture of metal construction materials; the occupations at highest risk are plumbers, pipe-fitters, and sheet-metal workers. The attributable risk fraction for occupational asbestos exposure in men was 83.2% (95% CI 76.8 to 89.6). The initial pathologist's diagnosis was confirmed in 67% of cases, ruled out in 13%, and left uncertain in the others; for half of the latter, the clinical findings supported a mesothelioma diagnosis. In all, 62% applied for designation of an occupational disease, and 91% of these were receiving workers' compensation.

CONCLUSIONS: The NMSP is a large scale epidemiological surveillance system with several original aspects, providing important information to improve the knowledge of malignant pleural mesothelioma, such as monitoring the evolution of its incidence, of high risk occupations and economic sectors, and improving pathology techniques.}, } @article {pmid16457433, year = {2005}, author = {Porta, C and Ardizzoni, A and Gaudino, G and Maio, M and Mutti, L and Pinto, C and Porru, S and Puntoni, R and Tassi, G and Tognon, M}, title = {Malignant mesothelioma in 2004: How advanced technology and new drugs are changing the perspectives of mesothelioma patients. Highlights from the VIIth Meeting of the International Mesothelioma Interest Group.}, journal = {La Medicina del lavoro}, volume = {96}, number = {4}, pages = {360-369}, pmid = {16457433}, issn = {0025-7818}, mesh = {Angiogenesis Inhibitors/therapeutic use ; Animals ; Antineoplastic Agents/therapeutic use ; Asbestos/adverse effects ; Carcinogens/toxicity ; Combined Modality Therapy/methods ; Cytokines/therapeutic use ; Genetic Therapy/methods ; Humans ; Immunotherapy/methods ; Mesothelioma/diagnosis/drug therapy/etiology/*therapy ; Pleural Neoplasms/diagnosis/drug therapy/etiology/*therapy ; Polyomavirus Infections/diagnosis/epidemiology/etiology/*therapy ; Protease Inhibitors/therapeutic use ; Protein Kinase Inhibitors/therapeutic use ; Risk Factors ; Simian virus 40/pathogenicity ; Societies, Medical ; Tumor Virus Infections/diagnosis/epidemiology/etiology/*therapy ; }, abstract = {Malignant mesothelioma (MMe) is a seemingly uncommon tumour whose incidence has in fact increased steadily and progressively over the last 30 years. Indeed, an actual "epidemic" is expected in the next 20 years, with over 1300 new cases a year till 2020 at least. Despite unquestionable improvement in the diagnostic methods at our disposal and the availability of new treatment strategies, the prognosis of MMe patients remains dramatically poor. For all the above reasons, translational research is the key to success; indeed, ever increasing knowledge of the molecular mechanisms underlying MMe pathogenesis could lead (and is actually leading) to new, hopefully more active, treatment options. To foster discussion among investigators working in this field, and to exchange different viewpoints concerning the newest advances in MMe pathogenesis and treatment, the VII International Mesothelioma Interest Group (IMIG) meeting was held in Brescia (Italy) between 24 and 26 June 2004 in cooperation with the Italian Group for the Study and Therapy of MMe (GIMe). The aim of this report is to summarize the most significant advances in the different disciplines applied to MMe presented and discussed during the IMIG meeting and how these advances will be changing the perspective of patients with MMe.}, } @article {pmid16457432, year = {2005}, author = {Pesatori, AC and Mensi, C}, title = {Peculiar features of mesothelioma occurrence as related to exposure patterns and circumstances in the Lombard Region, Italy.}, journal = {La Medicina del lavoro}, volume = {96}, number = {4}, pages = {354-359}, pmid = {16457432}, issn = {0025-7818}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Carcinogens/toxicity ; Female ; Humans ; Incidence ; Italy/epidemiology ; Male ; Mesothelioma/*diagnosis/epidemiology/etiology ; Middle Aged ; Occupational Diseases/*diagnosis/epidemiology/etiology ; Occupational Exposure/adverse effects ; Peritoneal Neoplasms/*diagnosis/epidemiology/etiology ; Pleural Neoplasms/*diagnosis/epidemiology/etiology ; Registries ; Retrospective Studies ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: The "Lombardy Mesothelioma Registry" started its activity in 2000 in accordance with Italian law DL 277/91.

OBJECTIVES AND METHODS: The Registry collects all new incident cases of Malignant Mesothelioma (MM) of pleura, peritoneum, pericardium and vaginal tunic of testis occurring in residents in the Lombardy Region (Northern Italy). For each "possible case" reported to the Registry by Lombardy hospitals, diagnosis is ascertained according to ISPESL Guidelines. For confirmed cases, a standardized questionnaire is administered to the subject or next-of-kin, to verify sources of lifetime asbestos exposure. Descriptive results are given for cases collected in 2000-2001. Age standardized incidence rates for the year 2000 were calculated for males and females.

RESULTS: After revision of clinical records, diagnosis was judged as "certain" MM in 307 (60%) subjects, probable in 63 (12%) and possible in 33 (6%) subjects. 21 were peritoneal mesothelioma. Standardized rates for pleural mesothelioma were respectively 3.7 and 1.4 per 100,000 for males and females. Occupational asbestos exposure was ascertained for 71% of male cases and 26% of females. Exposure was unknown in 11% and 27% of males and females respectively. The main relevant exposures were in building trades, metal manufacturing, machine production and maintenance; an unexpectedly high proportion of female cases was engaged in non-asbestos textile factories.

CONCLUSIONS: The high proportion of cases with unknown exposure underlines the need to explore new tools and sources to ascertain asbestos exposure. An ad hoc survey in textile industries showed exposure to asbestos to be widely spread in this industry.}, } @article {pmid16457431, year = {2005}, author = {Magnani, C}, title = {SV40, genetic polymorphism and mesothelioma. pathological and epidemiological evidence.}, journal = {La Medicina del lavoro}, volume = {96}, number = {4}, pages = {347-353}, pmid = {16457431}, issn = {0025-7818}, mesh = {Africa/epidemiology ; Animals ; Europe/epidemiology ; Humans ; Mesothelioma/epidemiology/genetics/*virology ; Pleural Neoplasms/epidemiology/genetics/*virology ; Poliovirus Vaccine, Inactivated/adverse effects ; *Polymorphism, Genetic ; Polyomavirus Infections/epidemiology/genetics/*virology ; Prevalence ; Simian virus 40/genetics/*pathogenicity ; Tumor Virus Infections/epidemiology/genetics/*virology ; United States/epidemiology ; }, abstract = {BACKGROUND: Asbestos exposure is the only cause of epidemiological relevance for pleural malignant mesothelioma (MM), but the mechanism of action is not entirely understood. A causal role was suggested for SV40 since viral DNA and proteins were detected in pleural MM and SV40 caused MM in hamsters. SV40 proteins (Tag) interact with oncogenes P53 and Rb.

OBJECTIVES: To review evidence on the association of SV40 with MM, bearing in mind laboratory and epidemiological studies.

METHODS: The review on SV40 was based on scientific papers published since 1990 on association of SV40 with human cancer.

RESULTS: Studies researching SV40 DNA in MM tissue observed a wide range of prevalences (0% to 70%); causes of variability were not convincingly identified. An association of MM with SV40 was suggested but confounding factors and biases were not considered. Cohort studies on humans inoculated with contaminated vaccines did not show an increased incidence but their statistical power was limited. Diffusion of SV40 in humans is linked to polio vaccines produced in 1955-63 from SV40-infected monkeys. A 11-12% prevalence of SV40 in adults were reported in the USA, 2-6% in Europe and Africa. The age pattern of MM does not suggest a cohort effect related to contaminated vaccines.

DISCUSSION: Association of SV40 with human MM is suggested from laboratory observations but still lacks confirmation in well designed epidemiological studies. Other putative co-factors in MM occurrence are mutations in genes involved in repair of damage caused by asbestos, notably DNA-repair genes. Preliminary observations are available but epidemiological studies are needed to test this hypothesis.}, } @article {pmid16457430, year = {2005}, author = {Nesti, M and Marinaccio, A and Gennaro, V and Gorini, G and Mirabelli, D and Mensi, C and Merler, E and Montanaro, F and Musti, M and Pannelli, F and Romanelli, A and Tumino, R and , }, title = {Epidemiologic surveillance for primary prevention of malignant mesothelioma: the Italian experience.}, journal = {La Medicina del lavoro}, volume = {96}, number = {4}, pages = {338-346}, pmid = {16457430}, issn = {0025-7818}, mesh = {Asbestos/adverse effects ; Carcinogens/toxicity ; Female ; Humans ; Italy/epidemiology ; Male ; Mesothelioma/epidemiology/etiology/*prevention & control ; Occupational Diseases/epidemiology/etiology/*prevention & control ; Occupational Exposure/adverse effects ; Peritoneal Neoplasms/epidemiology/etiology/*prevention & control ; Pleural Neoplasms/epidemiology/etiology/*prevention & control ; Population Surveillance/*methods ; Practice Guidelines as Topic ; Primary Prevention/*methods ; Retrospective Studies ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: The Italian National Mesothelioma Registry (ReNaM) was set up at the National Institute for Occupational Safety and Health (ISPESL) to estimate Italian incidence of malignant mesothelioma (MM), define modalities of asbestos exposures, assess impact and diffusion of MM, identify underestimated sources of environmental contamination.

OBJECTIVES: To describe ReNaM activity, database dimension and epidemiological characteristics of the caselist.

METHODS: Regional Operating Centers (COR) in 16 Italian regions were set up to identify and investigate all cases of MM diagnosed in each region, applying national guidelines. COR collect cases in health care institutions. Occupational history, lifestyle and residence are obtained by direct interview using a standard questionnaire. Exposure modalities are classified by industrial hygienists, evaluating whether work, private life or any particular environmental condition could have involved asbestos exposure.

RESULTS: Data refer to 3,446 cases collected in 9 Italian regions during 1993-2001. Pleural mesothelioma affected 94% cases, pleural/peritoneal ratio was 16:1. Gender ratio (M/F) was 2.7:1 (1.3:1 for peritoneum). There was a variety of occupational exposures, some already known as high risk sectors and others unexpected. The most common exposures occurred in building and construction, metallurgy and steel, shipbuilding, and railway stock. High risk categories were encountered such as bricklayers, plumbers, carpenters, electricians, welders, installers and maintenance workers in metallurgy and the steel industry, general labourers, tool makers and painters in shipbuilding/repair/demolition.

CONCLUSIONS: Despite some ReNam's limitations, identification of MM cases and analysis of modality of exposure, with standardized criteria, are a fundamental tool for primary prevention of asbestos related diseases.}, } @article {pmid16457429, year = {2005}, author = {Pasetto, R and Comba, P and Marconi, A}, title = {Mesothelioma associated with environmental exposures.}, journal = {La Medicina del lavoro}, volume = {96}, number = {4}, pages = {330-337}, pmid = {16457429}, issn = {0025-7818}, mesh = {Asbestos/*adverse effects ; Carcinogens/*toxicity ; Environmental Exposure/*adverse effects ; Global Health ; Humans ; Lung Neoplasms/epidemiology/*etiology ; Mesothelioma/epidemiology/*etiology ; Mineral Fibers ; Pleural Neoplasms/epidemiology/*etiology ; }, abstract = {BACKGROUND: The main sources of environmental, non-occupational exposure to asbestos or asbestiform fibres are: a) industrial plants in which asbestos was used in the production process; b) asbestos "in place" (mainly in buildings); c) contaminated soils. The association of these exposures with increasing risk of mesothelioma has been documented since 1960 in many places.

OBJECTIVES AND METHODS: The present paper is aimed at describing the main results of studies performed in the locations with soils naturally contaminated with asbestos or asbestiform fibres. Environmental exposure data and asbestos-related health outcomes, mainly mesothelioma, are analyzed through a review of the literature.

RESULTS: The sites with asbestos or other mesotheliomatogenous fibres in soils are characterized by low concentration levels of airborne fibres. Furthermore, exposure levels may increase when specific activities are carried out (mainly related to building construction), involving mechanical disturbance of fibre-containing materials. The type of fibres found are mainly amphiboles (tremolite). The population at risk of exposure is the general population, which can be exposed from birth. In these sites, the sex ratio of mesothelioma cases is close to 1.0 and the average age of cases ranges from 50 to 60 years.

CONCLUSIONS: Both "natural"and industrial environmental asbestos or asbestiform fibre exposures increase potential risk for mesothelioma. Strategies of environmental reclamation and risk communication should be implemented in these areas.}, } @article {pmid16457428, year = {2005}, author = {Porru, S and Placidi, D and Scotto di Carlo, A and Campagna, M and Mariotti, O and Barbieri, PG and Lombardi, S and Candela, A and Tassi, GF and Alessio, L}, title = {Malignant mesothelioma and the working environment: the viewpoint of the occupational physician.}, journal = {La Medicina del lavoro}, volume = {96}, number = {4}, pages = {312-329}, pmid = {16457428}, issn = {0025-7818}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Carcinogens/toxicity ; Environmental Exposure/adverse effects ; Evaluation Studies as Topic ; Female ; Humans ; Interviews as Topic ; Italy/epidemiology ; Male ; Mesothelioma/*diagnosis/epidemiology/etiology/therapy ; Middle Aged ; Occupational Diseases/*diagnosis/epidemiology/etiology/therapy ; *Occupational Medicine ; *Physician's Role ; Pleural Neoplasms/*diagnosis/epidemiology/etiology/therapy ; Registries ; Retrospective Studies ; }, abstract = {BACKGROUND: Firm scientific evidence supports the causal association between malignant mesothelioma (MM) and occupational exposure to asbestos. Risk attributable to occupation varies from 30 to 80% across different populations. The existence of a threshold level below which there is no risk of MM is still debated. A prompt and thorough assessment of exposure is essential to evaluate and manage MM cases, from diagnostic and epidemiological points of view.

OBJECTIVES AND METHODS: To highlight the multiple areas of intervention by Occupational Physicians (OP) in MM evaluation and management, to describe an experience of OP in the province of Brescia.

RESULTS: The main areas of interest of the OP are exposure assessment, diagnosis (clinical, etiological), medico-legal issues, social consequences, preventive strategies, risk communication, scientific dispute/uncertainties. By means of an active search, the Brescia MM registry, managed by OP belonging to the local health authority observed 309 MM from 1977 to 2003; the local Institute of Occupational Health, hosted in a hospital of national relevance, evaluated about 200 MM in the last decade. The main outcomes of OP activity are the high percentage of direct interviews, individual case management, expert exposure assessment, etiological diagnosis, counselling, medico-legal assistance, better knowledge of occupational risks, enhanced cooperation among health professionals (oncologists, pathologists, surgeons, pneumologists, general practitioners and OP), important contribution to Registries and to epidemiology (estimates of attributable risks, incidence, survival rates), with positive social and scientific consequences (insurance agencies, trade union organizations, public events, teaching opportunities).

CONCLUSIONS: This experience highlights the multifaceted role of OP in active research and evaluation of MM cases, in the context of a multidisciplinary approach.}, } @article {pmid16457427, year = {2005}, author = {Langård, S}, title = {Nordic experience: expected decline in the incidence of mesotheliomas resulting from ceased exposure?.}, journal = {La Medicina del lavoro}, volume = {96}, number = {4}, pages = {304-311}, pmid = {16457427}, issn = {0025-7818}, mesh = {Age Distribution ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Environmental Monitoring ; Epidemiological Monitoring ; Female ; Humans ; Incidence ; Inhalation Exposure ; Lung Neoplasms/*epidemiology/etiology/mortality ; Male ; Mesothelioma/*epidemiology/etiology/mortality ; Middle Aged ; Norway/epidemiology ; Pleural Neoplasms/*epidemiology/etiology/mortality ; Population Surveillance ; Registries ; Scandinavian and Nordic Countries/epidemiology ; Sex Distribution ; Time Factors ; }, abstract = {BACKGROUND: As a result mainly of information to workers and the public on prevention of effects of asbestos exposure, the use of asbestos for insulation was reduced to a minimum in the Nordic countries during the second half of the 1970's and the early 1980's. Stringent regulations when handling asbestos were introduced, and prohibition of use began in the early 1980's. Depending on the duration of the latency period between first exposure and the period of most intense exposure, a decline might be expected in the incidence of Malignant Mesothelioma (MM) 20-45 years after interruption of exposure.

OBJECTIVES: to describe the incidence of MM after cessation of asbestos exposure in Nordic countries.

METHODS: Nordic countries have cancer registers with information on all new cases of all cancers, over the past 4-6 decades. Cancer incidence data in these registers could describe long-term effects of interruption of asbestos exposure.

RESULTS: Current male and female incidence in Norway is about 1.5 x 10(-5)/year and 0.2 x 10(-5)/year respectively, and appears to be increasing. Based on personal observations among 32 MM cases, a number of which resulting from low total asbestos exposure with mean latency of about 45 years, examples are presented of the MM incidence in Nordic countries, illustrating when a significant decline in MM incidence may be expected.

CONCLUSIONS: 25 years after interruption of asbestos exposure, the expected rapid decline in MM incidence is still lacking, which appears to agree with population-based selection phenomena, with survival of a large pool of asbestos-exposed subjects with minimal exposure.}, } @article {pmid16457426, year = {2005}, author = {Bertazzi, PA}, title = {Descriptive epidemiology of malignant mesothelioma.}, journal = {La Medicina del lavoro}, volume = {96}, number = {4}, pages = {287-303}, pmid = {16457426}, issn = {0025-7818}, mesh = {Asbestos/adverse effects ; Carcinogens/toxicity ; Environmental Exposure/*adverse effects ; Global Health ; Humans ; Incidence ; Inhalation Exposure ; Lung Neoplasms/*epidemiology/etiology/mortality ; Mesothelioma/*epidemiology/etiology/mortality ; Occupational Diseases/*epidemiology/etiology/mortality ; Occupational Exposure/adverse effects ; Pleural Neoplasms/*epidemiology/etiology/mortality ; Risk Factors ; }, abstract = {BACKGROUND: Malignant mesothelioma (MM) is a rare cancer associated with exposure to asbestos, whose occurrence is increasing in industrialized countries.

OBJECTIVES: Describe and discuss: determinant factors, natural history, epidemic pattern, burden of MM to society at large, where interventions should be directed to change MM occurrence, gaps in knowledge.

METHODS: Review of the literature. Description of MM epidemiological features, with emphasis on risk, prognosis, control measures.

RESULTS: MM may be associated with low level asbestos exposure. Natural fibres other than asbestos possess the same carcinogenic potency. The estimated mean induction period is 25 years, and can be as long as 60 or more years. Survival is poor; current rates of MM in industrialized countries mirror past use of asbestos. In the USA, MM incidence increased steeply from the 1970's, peaked in 2000-2004, then levelled off and is expected to return to background levels by 2055. In the same period, the time-pattern for females was constant. Questions remain unanswered about the contribution of environmental asbestos exposure to MM occurrence. A gender effect has been described. The role of genetic and familial susceptibility is suggested by studies in Turkey. Sv40 has been proposed as co-factor in the asbestos-MM association. Controversy about the different hazards of different asbestos forms is still strong.

CONCLUSIONS: World production of asbestos has been declining dramatically in recent years, however increases have occurred in Asia. The decrease in asbestos use and a ban in several industrialized countries have proved effective in reducing the societal burden of MM.}, } @article {pmid16456138, year = {2006}, author = {Scherpereel, A and Grigoriu, B and Conti, M and Gey, T and Grégoire, M and Copin, MC and Devos, P and Chahine, B and Porte, H and Lassalle, P}, title = {Soluble mesothelin-related peptides in the diagnosis of malignant pleural mesothelioma.}, journal = {American journal of respiratory and critical care medicine}, volume = {173}, number = {10}, pages = {1155-1160}, doi = {10.1164/rccm.200511-1789OC}, pmid = {16456138}, issn = {1073-449X}, mesh = {Aged ; Analysis of Variance ; Area Under Curve ; Asbestosis/metabolism/mortality/*pathology ; Biomarkers, Tumor/analysis ; Diagnosis, Differential ; Disease Progression ; Female ; GPI-Linked Proteins ; Humans ; Male ; Membrane Glycoproteins/analysis/*metabolism ; Mesothelin ; Mesothelioma/blood/mortality/*pathology ; Middle Aged ; Neoplasm Staging ; Osteopontin ; Pleural Effusion, Malignant/*diagnosis/metabolism/mortality ; Pleural Neoplasms/blood/mortality/*pathology ; Prognosis ; Prospective Studies ; Sensitivity and Specificity ; Sialoglycoproteins/*metabolism ; Solubility ; Survival Analysis ; }, abstract = {BACKGROUND: Diagnosis of malignant pleural mesothelioma is a challenging issue. Potential markers in mesothelioma diagnosis include soluble mesothelin-related peptides (SMRPs) and osteopontin, but no subsequent validation has been published yet.

METHODS: We prospectively evaluated SMRPs in serum and pleural effusion from patients with mesothelioma (n = 74), pleural metastasis of carcinomas (n = 35), or benign pleural lesions associated with asbestos exposure (n = 28), recruited when first suspected for mesothelioma.

FINDINGS: Mean serum SMRP level was higher in patients with mesothelioma (2.05 +/- 2.57 nM/L [median +/- interquartile range]) than in patients with metastasis (1.02 +/- 1.79 nM/L) or benign lesions (0.55 +/- 0.59 nM/L). The area under the receiver operating characteristic curve (AUC) for serum SMRP was 0.872 for differentiating mesothelioma and benign lesions, cut-off = 0.93 nM/L (sensitivity = 80%, specificity = 82.6%). The AUC for serum SMRP differentiating metastasis and mesothelioma was 0.693, cut-off = 1.85 nM/L (sensitivity = 58.3%, specificity = 73.3%). SMRP values in pleural fluid were higher than in serum in all groups (mesothelioma: 46.1 +/- 83.2 nM/L; benign lesions: 6.4 +/- 11.1 nM/L; metastasis: 6.36 +/- 21.73 nM/L). The AUC for pleural SMRP-differentiating benign lesions and mesothelioma was 0.831, cut-off = 10.4 nM/L (sensitivity = 76.7%, specificity = 76.2%). The AUC for pleural SMRP-differentiating metastasis and mesothelioma was 0.793.

INTERPRETATION: We show that SMRPs may be a promising marker for mesothelioma diagnosis when measured either in serum or pleural fluid. The diagnostic value of SMRPs was similar in both types of samples, but pleural fluid SMRPs may better discriminate mesothelioma from pleural metastasis.}, } @article {pmid16447785, year = {2005}, author = {Inase, N and Tominaga, S and Yasui, M and Tsukada, Y and Oukouchi, M and Miura, H}, title = {[Adenosine deaminase 2 in the diagnosis of tuberculous pleuritis].}, journal = {Kekkaku : [Tuberculosis]}, volume = {80}, number = {12}, pages = {731-734}, pmid = {16447785}, issn = {0022-9776}, mesh = {Adaptor Proteins, Signal Transducing/*analysis ; Adenosine Deaminase/*analysis ; Adult ; Aged ; Aged, 80 and over ; Clinical Enzyme Tests ; DNA-Binding Proteins ; Female ; Humans ; Isoenzymes ; Male ; Middle Aged ; Pleural Effusion ; Sensitivity and Specificity ; Transcription Factors/*analysis ; Tuberculosis, Pleural/*diagnosis/enzymology ; }, abstract = {PURPOSE: We examined the usefulness of adenosine deaminase 2 (ADA2) in the diagnosis of tuberculous pleuritis.

SUBJECTS: A hundred cases, 78 male and 22 female, with pleural effusion were examined. With regard to pleural effusion, 18 cases were transudate and 82 cases (9 tuberculous pleuritis, 27 lung cancer, 8 mesothelioma, 5 malignant diseases except lung cancer and mesothelioma, 5 benign asbestos pleurisy, 10 empyema, 10 parapneumonic effusion, one SLE, one parasitic infection, and 6 undetermined etiology) were exudates. The last 6 cases with unknown origin were excluded in this study.

RESULTS: Pleural adenosine deaminase (ADA) was 90.4 +/- 22.4 U/l (mean +/- SD) and pleural ADA2 was 80.4 +/- 21.9 U/l in tuberculous pleuritis, both were significantly higher than those in non-tuberculous exudates (p < 0.001). In the diagnosis of tuberculous pleuritis, pleural ADA showed 100% sensitivity and 88% specificity, whereas pleural ADA2 showed 100% sensitivity and 91% specificity.

CONCLUSION: Pleural ADA2 is useful in the diagnosis of tuberculous pleuritis, which has similar sensitivity and a little better specificity compared with pleural ADA.}, } @article {pmid16437396, year = {2005}, author = {Ambrosini, V and Rubello, D and Nanni, C and Farsad, M and Castellucci, P and Franchi, R and Fabbri, M and Rampin, L and Crepaldi, G and Al-Nahhas, A and Fanti, S}, title = {Additional value of hybrid PET/CT fusion imaging vs. conventional CT scan alone in the staging and management of patients with malignant pleural mesothelioma.}, journal = {Nuclear medicine review. Central & Eastern Europe}, volume = {8}, number = {2}, pages = {111-115}, pmid = {16437396}, issn = {1506-9680}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Image Enhancement/methods ; Male ; Mesothelioma/*diagnostic imaging ; Middle Aged ; Neoplasm Staging ; Pleural Neoplasms/*diagnostic imaging ; Positron-Emission Tomography/*methods ; Prognosis ; Reproducibility of Results ; Sensitivity and Specificity ; *Subtraction Technique ; Tomography, X-Ray Computed/*methods ; }, abstract = {BACKGROUND: Despite being a relatively rare disease, the incidence of malignant pleural mesothelioma (MPM) is expected to increase over the next two decades due to the long time interval elapsing between exposure to causative factors, mainly asbestos, and disease onset. Early disease stages have been reported to benefit from radical surgery. In more advanced disease stages, a multimodality treatment, including various combinations of chemotherapy, external radiotherapy and surgery, may provide some favourable results though the prognosis remains poor. In this regard, an accurate pre-treatment staging plays an important role in offering patients a more appropriate therapeutic planning. In some preliminary studies, (18)F-FDG PET has proven to be able to provide useful information for staging purpose, especially for the detection of metastatic spread to lymph nodes and distant sites.

MATERIAL AND METHODS: In the present study, we investigated 15 consecutive patients with histologically proven MPM by means of conventional 2-mm thickness whole-body CT scan with and without contrast medium in comparison with wholebody (18)F-FDG PET/CT fusion imaging.

RESULTS: (18)F-FDG PET/CT did not provide additional information about the primary tumour (T) compared to CT scan, but identified a higher number of metastatic mediastinal lymph nodes (N) in 6 patients (40% of cases) and unknown metastatic disease to distant sites (M) in 3 patients (20% of cases). On the basis of PET/CT findings, treatment planning was changed in 5 patients (33.3% of cases).

CONCLUSIONS: Our data show that (18)F-FDG PET/CT fusion imaging can play a relevant role in the staging and treatment planning of MPM patients.}, } @article {pmid16434923, year = {2005}, author = {Imbernon, E and Marchand, JL and Garras, L and Goldberg, M}, title = {[Quantitative assessment of the risk of lung cancer and pleural mesothelioma among automobile mechanics].}, journal = {Revue d'epidemiologie et de sante publique}, volume = {53}, number = {5}, pages = {491-500}, doi = {10.1016/s0398-7620(05)84726-1}, pmid = {16434923}, issn = {0398-7620}, mesh = {Adolescent ; Adult ; Air Pollutants, Occupational/adverse effects ; Asbestos/adverse effects ; *Automobiles ; Computer Simulation ; France/epidemiology ; Humans ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Models, Biological ; Occupational Diseases/*epidemiology ; Occupational Exposure ; Pleural Neoplasms/*epidemiology ; Risk Assessment ; Time Factors ; }, abstract = {BACKGROUND: A quantitative assessment of the risk of lung cancer and pleural mesothelioma among mechanics exposed to dust released from automobile asbestos-containing parts was performed.

METHODS: The population of automobile mechanics in France, according to profession and industrial sectors codes, was estimated from the data of the 1999 census. Risks were computed for a total male population of 242,360 automobile mechanics aged 16 to 60 years. Exposure to asbestos among these workers comes from maintenance tasks involving asbestos-containing parts produced before 1997 (date of the asbestos ban in France). Airborne asbestos concentration data available from the literature were highly variable. No data reporting the distribution of time spent for such tasks over a typical week of work were available. Therefore, different weekly exposure profiles were simulated, based on data from the 1994 SUMER survey. Risk models were those used for assessing asbestos health effects by all national and international agencies. Exposure scenarios mixed different levels of exposure, periods of time, proportions of exposed workers and dates of the "natural" disappearance of the automobile fleet built before asbestos was banned in brakes and other parts. The most realistic scenario hypothesizes that all automobile mechanics were exposed to asbestos, that the exposure levels ranged from 0.06 and 0.25 fibers/liter per week for the period before 1997, and between 0.01 and 0.06 fibers/liter per week afterwards until 2010.

RESULTS: According to this scenario, the number of lifelong cancer deaths (lung and pleura) induced by asbestos exposure in this population is estimated at 602 "unavoidable" cases, due to exposure experienced before 2003; 43 other cases will occur if asbestos is not removed from existing automobiles.}, } @article {pmid16422024, year = {2006}, author = {Hiraki, A and Aoe, K and Ueoka, H}, title = {Asbestos exposure and serum osteopontin.}, journal = {The New England journal of medicine}, volume = {354}, number = {3}, pages = {304-5; author reply 304-5}, pmid = {16422024}, issn = {1533-4406}, mesh = {Area Under Curve ; *Asbestos ; Biomarkers/analysis ; Humans ; Mesothelioma/*diagnosis/pathology ; Occupational Exposure ; Osteopontin ; Pleural Effusion/*chemistry ; Pleural Neoplasms/*diagnosis/pathology ; Sialoglycoproteins/*analysis ; }, } @article {pmid16421377, year = {2006}, author = {O'Regan, AW and Serlin, D and Berman, JS}, title = {Asbestos exposure and serum osteopontin.}, journal = {The New England journal of medicine}, volume = {354}, number = {3}, pages = {304-5; author reply 304-5}, doi = {10.1056/NEJMc053112}, pmid = {16421377}, issn = {1533-4406}, mesh = {*Asbestos ; Biomarkers/blood ; Cohort Studies ; Humans ; Mesothelioma/*blood/diagnosis ; Occupational Exposure ; Osteopontin ; Pleural Neoplasms/*blood/diagnosis ; Sialoglycoproteins/*blood ; }, } @article {pmid16405672, year = {2006}, author = {Suvarna, SK and Layton, C}, title = {What is a significant lung asbestos fibre result?.}, journal = {Histopathology}, volume = {48}, number = {2}, pages = {203-204}, doi = {10.1111/j.1365-2559.2005.02203.x}, pmid = {16405672}, issn = {0309-0167}, mesh = {Aged ; Asbestos/*analysis ; Female ; Humans ; Lung/*metabolism/pathology/ultrastructure ; Lung Neoplasms/metabolism ; Male ; Mesothelioma/metabolism ; Microscopy, Electron ; Mineral Fibers/analysis ; Occupational Exposure/*analysis ; Occupational Health/statistics & numerical data ; Pulmonary Fibrosis/metabolism ; Reference Values ; Reproducibility of Results ; Risk Assessment/methods/statistics & numerical data ; United Kingdom ; }, } @article {pmid16400322, year = {2006}, author = {Ordóñez, NG}, title = {Mesothelioma with rhabdoid features: an ultrastructural and immunohistochemical study of 10 cases.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {19}, number = {3}, pages = {373-383}, doi = {10.1038/modpathol.3800543}, pmid = {16400322}, issn = {0893-3952}, mesh = {Aged ; Calbindin 2 ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; Keratin-7 ; Keratins/analysis ; Male ; Mesothelioma/metabolism/*pathology/ultrastructure ; Microscopy, Electron ; Middle Aged ; Pleural Neoplasms/metabolism/*pathology/ultrastructure ; Rhabdoid Tumor/metabolism/*pathology/ultrastructure ; S100 Calcium Binding Protein G/analysis ; Survival Analysis ; Vimentin/analysis ; }, abstract = {Mesotheliomas with rhabdoid morphology are rare and only two individual case reports have been documented in the literature. This author reports a series of 10 cases of mesotheliomas with rhabdoid features, nine of which originated in the pleura and one in the peritoneum. Eight of the patients were men and two were women. Six patients had a history of asbestos exposure. Histologically, seven of the mesotheliomas were epithelioid, two sarcomatoid, and one biphasic. The proportion of the rhabdoid cells seen in these cases constituted 15-75% of the individual tumors. Cytoplasmic staining in the rhabdoid cells was seen for pan-keratin and vimentin in all 10 cases, for keratin 7 in eight of eight, for calretinin in nine of 10, and for keratin 5/6 in seven of nine. Nuclear positivity for WT1 was observed in the rhabdoid cells of four of seven cases and membranous reactivity for mesothelin in four of six, and for podoplanin in two of six. Only one case showed desmin positivity in sparse cells in the nonrhabdoid component of the tumor. All of the cases were negative for CEA, MOC-31, TAG-72, CD15, CD34, bcl2, muscle-specific actin, and TTF-1. Ultrastructural studies revealed paranuclear collections of intermediate filaments, but no evidence of rhabdomyoblastic differentiation was seen. The mean survival of five of the six patients for whom this information was available was 3.8 months. The remaining patient had a survival time of 1 year. It is important for pathologists to be aware that mesotheliomas can present rhabdoid features, not only because they can be confused with other malignancies that can exhibit a similar morphology, but also because of their apparently unusually aggressive behavior. The value of immunohistochemistry and electron microscopy in the differential diagnosis of these tumors is discussed.}, } @article {pmid16363443, year = {2005}, author = {Engholm, G and Englund, A}, title = {Asbestos hazard in the Swedish construction industry--recent trends in mesothelioma incidence.}, journal = {Scandinavian journal of work, environment & health}, volume = {31 Suppl 2}, number = {}, pages = {27-30}, pmid = {16363443}, issn = {0355-3140}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Cohort Studies ; *Facility Design and Construction ; Female ; Humans ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; *Occupational Exposure ; Pleural Neoplasms/*epidemiology/etiology ; Sweden/epidemiology ; }, abstract = {OBJECTIVES: The aim of this study was to analyze the incidence of pleural tumors among various categories of Swedish construction workers and to determine to what extent its change over time differs from that of the general male population.

METHODS: Traditional methods have been used to study cancer incidence through 1998 in a cohort comprising 370 165 male workers examined in 1971-1992 by Bygghälsan, an organization at the time providing nationwide occupational health service. Incidence was assessed by linkage to the national cancer register.

RESULTS: Swedish construction workers, particularly those heavily exposed to asbestos, had an excess incidence of pleural tumors in 1975-1998 [standardized incidence ratio (SIR) 3.16, 95% confidence interval (95% CI) 2.55-3.88]. The excess declined with subsequent follow-up periods and birth cohorts with the exception of the most recent period (SIR 3.83, 95% CI 2.64-5.38) and those borne in the 1930s.

CONCLUSIONS: A possible decline in pleural tumors among men following the cessation of asbestos use 25 years earlier in the population at large may not be applicable to an end-user sector like construction work. In occupations charged with repairing and refurbishing work, there may even have been an increase lately.}, } @article {pmid16362942, year = {2006}, author = {Murayama, T and Takahashi, K and Natori, Y and Kurumatani, N}, title = {Estimation of future mortality from pleural malignant mesothelioma in Japan based on an age-cohort model.}, journal = {American journal of industrial medicine}, volume = {49}, number = {1}, pages = {1-7}, doi = {10.1002/ajim.20246}, pmid = {16362942}, issn = {0271-3586}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Cohort Studies ; Europe/epidemiology ; Forecasting ; Humans ; Japan/epidemiology ; Male ; Mesothelioma/*etiology/mortality ; Middle Aged ; Models, Statistical ; Occupational Diseases/*etiology/mortality ; Pleural Neoplasms/*etiology/mortality ; Time Factors ; }, abstract = {BACKGROUND: Japanese consumption of asbestos increased rapidly after the 1950s and lingered at a high level while the world's consumption decreased substantially after the 1980s. Mesothelioma is due primarily to asbestos, and the number of deaths in Japan is expected to increase in the future.

METHOD: We estimated the future number of pleural mesothelioma deaths among males in Japan using an age-cohort model.

RESULTS: Analyses showed that there would be about 100,000 deaths in Japan due to pleural mesothelioma in the next 40 years. Compared with the statistics in European countries, the ratio of expected death numbers to the population size is remarkably close to linear. The data-point for Japan was slightly lower than that which could be expected from the linear relationship.

CONCLUSIONS: The limited availability of data may result in underestimation. Taking into consideration the consumption pattern of asbestos in recent decades, the incorporation of later cohorts will improve the estimation.}, } @article {pmid16350470, year = {2005}, author = {Egilman, DS and Billings, MA}, title = {Abuse of epidemiology: automobile manufacturers manufacture a defense to asbestos liability.}, journal = {International journal of occupational and environmental health}, volume = {11}, number = {4}, pages = {360-371}, doi = {10.1179/oeh.2005.11.4.360}, pmid = {16350470}, issn = {1077-3525}, mesh = {Asbestos/*adverse effects ; *Automobiles ; Causality ; Epidemiologic Methods ; Humans ; Industry/*legislation & jurisprudence/*statistics & numerical data ; *Liability, Legal ; Mesothelioma/epidemiology/etiology ; Occupational Exposure/adverse effects/legislation & jurisprudence ; Science/statistics & numerical data ; }, abstract = {Much of the "debate" about the relationship between asbestos exposure from automobile brake work and asbestos-induced cancer has been fueled by studies that have been funded by corporations with billions at stake in tort litigation. The authors explore how asbestos-lined brake manufacturers have corrupted medical literature to escape liability, analyzing studies funded by these companies to enable them to claim that work with asbestos brake linings never causes mesothelioma. They reveal how the companies have redefined scientific criteria for the determination of cause-effect relationships and manipulated scientific data to give the impression of an absence of effect. But the absence of evidence is not evidence of the absence of an effect.}, } @article {pmid16343925, year = {2006}, author = {Neragi-Miandoab, S}, title = {Multimodality approach in management of malignant pleural mesothelioma.}, journal = {European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery}, volume = {29}, number = {1}, pages = {14-19}, doi = {10.1016/j.ejcts.2005.10.008}, pmid = {16343925}, issn = {1010-7940}, mesh = {Antimetabolites, Antineoplastic/therapeutic use ; Antineoplastic Agents/therapeutic use ; Cisplatin/therapeutic use ; Combined Modality Therapy/methods ; Deoxycytidine/analogs & derivatives/therapeutic use ; Drug Therapy, Combination ; Genetic Therapy/methods ; Humans ; Immunotherapy/methods ; Mesothelioma/drug therapy/radiotherapy/*therapy ; Palliative Care/methods ; Pleural Neoplasms/drug therapy/radiotherapy/*therapy ; Thoracic Surgical Procedures/mortality ; Treatment Outcome ; Gemcitabine ; }, abstract = {Malignant pleural mesothelioma (MPM) is a solid, locally aggressive tumor, which has been closely linked to asbestos exposure. The survival rate without treatment ranges from 4 to 12 months. Response to chemotherapy and radiation is poor, and surgery is the most effective therapy. There are currently 3000 new MPM cases per year in the United States, with the peak incidence in the United States and Europe expected to occur in the year 2020. The prognosis depends on the stage of the tumor at the time of diagnosis, its histological type, lymph node status, and resection margins. While the diagnosis is often delayed, earlier intervention may improve life expectancy. Single-modality therapy has not been effective in changing the natural history of MPM. As a result, multimodality regimens involving surgery with radiation, chemotherapy, or immunotherapy have been initiated. Multiple modality approach has demonstrated favorable outcome, particularly in patients with epithelial histology, negative resection margins and presence of no metastases to extrapleural lymph nodes. Cisplatin and mitomycin have demonstrated modest efficacy in management of distant tumor recurrence. Cisplatin and gemcitabine regimen as well as cisplatin/pemetrexed followed by 54 Gy of adjuvant hemithorax radiation have been reported to improve the outcome.}, } @article {pmid16341811, year = {2005}, author = {Baser, ME and Rai, H and Wallace, AJ and Evans, DG}, title = {Neurofibromatosis 2 (NF2) and malignant mesothelioma in a man with a constitutional NF2 missense mutation.}, journal = {Familial cancer}, volume = {4}, number = {4}, pages = {321-322}, pmid = {16341811}, issn = {1389-9600}, mesh = {Aged ; Asbestos/adverse effects ; *Genes, Neurofibromatosis 2 ; Humans ; Male ; Mesothelioma/*complications/*genetics ; Mutation, Missense ; Neurofibromatosis 2/complications/*genetics ; Neuroma, Acoustic/etiology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/complications/*genetics ; Polymerase Chain Reaction ; }, abstract = {Neurofibromatosis 2 (NF2) is caused by inactivating mutations of the NF2 tumor suppressor gene. Somatic NF2 mutations also occur in a high proportion of human primary malignant mesotheliomas. We report an elderly man with NF2, malignant mesothelioma, and a constitutional NF2 missense mutation. The long latent period for mesothelioma in this patient (61 years) raises the possibility that the type of mutant NF2 allele could affect mesothelioma tumorigenesis or progression.}, } @article {pmid16334033, year = {2005}, author = {Gong, Y and Ren, R and Ordóñez, NG and Sun, X and Sneige, N}, title = {Fine needle aspiration cytology of well-differentiated papillary mesothelioma: a case report.}, journal = {Acta cytologica}, volume = {49}, number = {5}, pages = {537-542}, doi = {10.1159/000326202}, pmid = {16334033}, issn = {0001-5547}, mesh = {Biopsy, Fine-Needle ; Carcinoma/diagnostic imaging/pathology ; Diagnosis, Differential ; Diagnostic Errors/prevention & control ; Epithelial Cells/pathology/ultrastructure ; Epithelium/pathology/ultrastructure ; Female ; Humans ; Liver/pathology ; Liver Neoplasms/diagnostic imaging/*pathology/ultrastructure ; Mesothelioma/diagnostic imaging/*pathology/ultrastructure ; Microscopy, Electron, Transmission ; Middle Aged ; Peritoneal Neoplasms/diagnostic imaging/*pathology/ultrastructure ; Tomography, X-Ray Computed ; }, abstract = {BACKGROUND: Well-differentiated papillary mesothelioma (WDPM) is an uncommon subtype of mesothelioma that typically occurs in the peritoneum of women without a history of asbestos exposure and usually follows an indolent clinical course. Fine needle aspiration (FNA) of this type of tumor has rarely been reported.

CASE: A 64-year-old woman with 11-year history of colon cancer and an adrenal nodule was found, on abdominal computed tomography, to have a mass in the right lobe of the liver. Aspirates of the mass were composed of abundant, tight, papillary groups, monolayered, pavementlike sheets; and scattered single cells with minimal atypia. The cell block showed a predominantly papillary growth pattern and a single layer of bland, cuboidal to flattened covering cells with stout, fibrovascular cores containing clusters of foamy histiocytes. Tumor cells in the focal tubulopapillary and solid areas were mingled with inflammatory cells and showed slightly more atypia than did the cells covering the papillae. The differential diagnoses were intrahepatic papillary neoplasm, including well-differentiated mesothelioma and metastatic low grade papillary serous carcinoma. At surgery the tumor was found to be a pedunculated peritoneal mass that arose from the posterior surface of the right lobe of the liver. The mesothelial origin of the tumor was confirmed by both immunoperoxidase study and electron microscopic examination, which demonstrated long, slender, branching microvilli.

CONCLUSION: Familiarity with the cytomorphologic features and clinical presentation of WDPM, knowledge of the exact anatomic location and consideration of the appropriate differential diagnosis combined with ancillary studies are the keys to an accurate diagnosis.}, } @article {pmid16332304, year = {2005}, author = {Pavia, R and Mondello, B and Barone, M and Surleti, S and Puliafito, M and Barresi, P}, title = {[Malignant pleural mesothelioma: early diagnosis and multimodality management].}, journal = {Il Giornale di chirurgia}, volume = {26}, number = {6-7}, pages = {257-260}, pmid = {16332304}, issn = {0391-9005}, mesh = {Adult ; Aged ; Aged, 80 and over ; Combined Modality Therapy ; Early Diagnosis ; Female ; Humans ; Male ; Mesothelioma/*diagnosis/*therapy ; Middle Aged ; Pleural Neoplasms/*diagnosis/*therapy ; }, abstract = {Malignant pleural mesothelioma (MPM) is a cancer with a poor prognosis, and its incidence increase, mainly as a result of exposure to asbestos. Universally acknowledged therapeutic approaches still don't exist at the moment, because of its refractory behaviour to all standard therapies; treatment protocols inclusive of either surgery, radiotherapy or chemotherapy have been largely employed, but usually with little impact on survival. For potentially operable pleural mesotheliomas new treatments tend to combine surgery both with new chemotherapy drugs and radiotherapy, in order to improve remarkably survival rates in selected cases. Other approaches, i.e. palliative, proved to be useful in the treatment of two major symptoms, namely dyspnea and thoracic pain. In this work the Authors are reporting their experience with malignant pleural mesothelioma, stressing the role of videothoracoscopy in the early diagnosis, weighing the radical cancer resection option and the effectiveness of multimodal treatment.}, } @article {pmid16326244, year = {2005}, author = {Patel, SN and Kettner, NW}, title = {Malignant pleural mesothelioma: a case report.}, journal = {Journal of manipulative and physiological therapeutics}, volume = {28}, number = {9}, pages = {724-729}, doi = {10.1016/j.jmpt.2005.09.004}, pmid = {16326244}, issn = {1532-6586}, mesh = {Aged ; Asbestos/adverse effects ; Female ; Humans ; Mesothelioma/etiology/*physiopathology/surgery ; Pleural Neoplasms/etiology/*physiopathology/surgery ; }, abstract = {OBJECTIVE: The aim of this study was to discuss a case of malignant pleural mesothelioma (MPM) that presented to a chiropractic teaching clinic and review the pathophysiology of diseases associated with asbestos exposure.

CLINICAL FEATURES: An 86-year-old woman had right-sided back pain at the thoracolumbar junction for 3 months; this pain prevented her from exercising on a daily basis. She was alert and oriented but in obvious distress because of her back pain. Breath sounds were decreased on the right in the posterior and lower lobes, with dull percussion and increased tactile fremitus. A significant collection of pleural effusion was seen on the right side on plain film radiographs. A chest computed tomography with contrast showed a large right-sided pleural effusion with small consolidation at the right lung base suggestive of pleural or pulmonary malignancy and highly suspicious for MPM. Further questioning about asbestos exposure revealed that her husband was a maintenance worker. An extrapleural pneumonectomy was performed, and specimens of parietal and visceral pleura were sent for pathological, which revealed a definitive diagnosis of spindle cell mesothelioma.

INTERVENTION AND OUTCOME: The patient was diagnosed with MPM, and a surgical therapy option was considered because of the aggressive nature of the lesion and her advanced age. An extrapleural pneumonectomy was performed with removal of parietal and visceral pleura, right lower lobe, and right hemidiaphragm.

CONCLUSION: This is an unusual case of advanced MPM that is most likely from indirect asbestos exposure.}, } @article {pmid16325122, year = {2005}, author = {Steele, JP}, title = {Prognostic factors for mesothelioma.}, journal = {Hematology/oncology clinics of North America}, volume = {19}, number = {6}, pages = {1041-52, vi}, doi = {10.1016/j.hoc.2005.09.009}, pmid = {16325122}, issn = {0889-8588}, mesh = {Humans ; Mesothelioma/*diagnosis/mortality/therapy ; Prognosis ; Survival Analysis ; Treatment Outcome ; }, abstract = {Our understanding of malignant mesothelioma has increased rapidly in the last 5 years. The prognosis remains poor for most patients, however. Radical surgery is inappropriate for most, and palliative chemotherapy can be toxic if used without care. Patient selection is crucial, and prognostic factors allow us to predict which patients are likely to benefit from intensive treatment. Longer survival is associated with epithelioid histology, earlier stage, female gender, left-sided primary, nonexposure to asbestos, no history of smoking, and a lack of symptoms at presentation. Numerous genes of significance are identified and many have been shown to correlate with clinical outcome. Molecular data will provide prognostication of exceptional accuracy, biologic insights, and targets for improved treatment.}, } @article {pmid16325121, year = {2005}, author = {Creaney, J and Robinson, BW}, title = {Detection of malignant mesothelioma in asbestos-exposed individuals: the potential role of soluble mesothelin-related protein.}, journal = {Hematology/oncology clinics of North America}, volume = {19}, number = {6}, pages = {1025-40, v}, doi = {10.1016/j.hoc.2005.09.007}, pmid = {16325121}, issn = {0889-8588}, mesh = {Asbestos/*adverse effects ; Biomarkers, Tumor/blood ; Environmental Exposure/adverse effects ; Female ; GPI-Linked Proteins ; Humans ; Male ; Mass Screening/methods ; Membrane Glycoproteins/blood/physiology ; Mesothelin ; Mesothelioma/*diagnosis/*etiology ; Ovarian Neoplasms/diagnosis ; }, abstract = {Malignant mesothelioma (MM) is strongly associated with asbestos exposure. Measurement of soluble mesothelin-related protein (SMRP) levels in the serum may prove valuable as an adjunct to current tests for the diagnosis of MM and for monitoring MM patients for the early detection of disease recurrence. SMRP measures also may be useful in an overall screening program for MM because early results show that some individuals have elevated levels 1 to 4 years before symptom development. Although individuals with occupational and nonoccupational asbestos exposure are justifiably concerned about their risk of developing MM, consideration must be given to the complex issues surrounding screening for this disease, and a more substantial evaluation of the SMRP marker must be undertaken before deciding to promote a screening program.}, } @article {pmid16319530, year = {2005}, author = {Lecomte, C and Andujar, P and Renier, A and Kheuang, L and Abramowski, V and Mellottee, L and Fleury-Feith, J and Zucman-Rossi, J and Giovannini, M and Jaurand, MC}, title = {Similar tumor suppressor gene alteration profiles in asbestos-induced murine and human mesothelioma.}, journal = {Cell cycle (Georgetown, Tex.)}, volume = {4}, number = {12}, pages = {1862-1869}, doi = {10.4161/cc.4.12.2300}, pmid = {16319530}, issn = {1551-4005}, mesh = {Animals ; Asbestos/*toxicity ; DNA Mutational Analysis ; *Gene Expression Profiling ; *Genes, Tumor Suppressor ; Humans ; Mesothelioma/*chemically induced/*genetics/pathology ; Mice ; Mice, Knockout ; Mutation ; Tumor Cells, Cultured ; Tumor Suppressor Proteins ; }, abstract = {Human malignant mesothelioma (HMM) is an aggressive malignancy mainly caused by exposure to asbestos fibers. Here we investigated tumor suppressor genes in mesothelioma cells from tumoral ascites developed in mice exposed to asbestos (asb) fibers and in 12 HMM cell cultures. Mutations in Nf2, p16/Cdkn2a, p19/Arf and Trp53 genes and protein expression of p15/Cdkn2b and Cdk4 were analyzed in 12 cultures from mice hemizygous for Nf2 (asb-Nf2(KO3/+)) and 4 wild type counterparts (asb-Nf2(+/+)). We have found frequent inactivations of p16/Cdkn2a, p19/Arf (or P14/ARF) and p15/Cdkn2b, coinactivation of p16/Cdkn2a and p15/Cdkn2b and low rate of Trp53 mutations in both asb-Nf2(KO3/+) and asb-Nf2(+/+) mesothelioma cells. In both mouse and human mesothelioma cells, inactivation of the hortologous genes p16/Cdkn2a or P16/CDKN2A was due to deletions at the Ink4/Arf locus encompassing p19/Arf or P14/ARF, respectively. Loss of heterozygosity at the Nf2 locus was detected in 10 of 11 asb-Nf2(KO3/+) cultures and Nf2 gene rearrangement in one asb-Nf2(+/+) culture. These data show that the profile of TSG alterations in asbestos-induced mesothelioma is similar in mice and humans. Thus, the mouse mesothelioma model could be useful for human risk assessment, taking into account interindividual variations in genetic sensitivity to carcinogens.}, } @article {pmid16316830, year = {2005}, author = {Mohr, S and Keith, G and Rihn, B}, title = {[Asbestos and malignant pleural mesothelioma: molecular, cellular and physiopathological aspects].}, journal = {Bulletin du cancer}, volume = {92}, number = {11}, pages = {959-976}, pmid = {16316830}, issn = {1769-6917}, mesh = {Asbestos/*adverse effects ; Cell Division ; Cell Transformation, Neoplastic ; Chromosome Aberrations ; Combined Modality Therapy ; DNA Damage ; Gene Expression Regulation, Neoplastic ; Humans ; Incidence ; Inhalation Exposure ; Mesothelioma/epidemiology/*etiology/genetics/physiopathology/therapy ; Mineral Fibers/adverse effects ; Occupational Diseases/epidemiology/etiology/genetics/physiopathology ; Pleural Neoplasms/epidemiology/*etiology/genetics/physiopathology/therapy ; Prognosis ; RNA, Messenger/genetics ; RNA, Neoplasm/genetics ; Transcription, Genetic ; }, abstract = {Asbestos is known as mutagenic and carcinogenic for human and is responsible for many pulmonary diseases including asbestosis, bronchogenic carcinoma and malignant pleural mesothelioma. Occupational exposure to asbestos is involved in 70-80% of all malignant pleural mesothelioma. The later presents a growing challenge for both researcher and clinician. The diagnosis of malignant pleural mesothelioma is difficult and the current treatments did not show significant improvement of the survival. The increasing incidence of malignant pleural mesothelioma, its gravity and its human, social and financial consequences are of high concern in public health. In this paper we summarize the so far knowledge on cellular, molecular and pathophysiological events involved in genesis and development of malignant pleural mesothelioma. Finally, the paper also report recent data sourced from the study of malignant pleural mesothelioma transcriptome using high-throughput technologies such as gene expression array. These data should improve the accuracy of mesothelioma diagnosis and therapy.}, } @article {pmid16308104, year = {2005}, author = {Kayser, K and Trott, J and Böhm, G and Huber, M and Kaltner, H and André, S and Gabius, HJ}, title = {Localized fibrous tumors (LFTs) of the pleura: clinical data, asbestos burden, and syntactic structure analysis applied to newly defined angiogenic/growth-regulatory effectors.}, journal = {Pathology, research and practice}, volume = {201}, number = {12}, pages = {791-801}, doi = {10.1016/j.prp.2005.09.002}, pmid = {16308104}, issn = {0344-0338}, mesh = {Adult ; Aged ; Antigens, CD34/analysis ; Asbestos/analysis ; Biomarkers, Tumor/analysis ; Female ; Humans ; Immunohistochemistry ; Macrophage Migration-Inhibitory Factors/analysis ; Male ; Middle Aged ; Neoplasms, Fibrous Tissue/*chemistry/*diagnosis/pathology ; Neovascularization, Physiologic ; Pleural Neoplasms/*diagnosis/*metabolism/pathology ; Vimentin ; }, abstract = {This study was performed to add clinical data, to introduce new markers, and to perform syntactic structural analysis on localized fibrous tumors (LFTs) of the pleura. The material comprised clinical data and processed sections obtained from 36 patients. The results achieved from quantitative imaging techniques and syntactic structure analysis were correlated with clinical data, including patients' habits (smoking), asbestos exposure, survival, and tumor recurrence. The disease caused increasing chest pain and dyspnea in 47% of patients. Exposure to asbestos was noted in 13 out of 36 patients, whereas smoking posed no major risk factor. Two patients developed a recurrent tumor after 8 and 42 months, respectively; none of the other patients died of this tumor disease within the follow-up period of maximal 212 months. The cases were clearly discriminated from mesotheliomas by the marker profile. Frequent expression of accessible ligands for endogenous lectins galectins-1 and -3, the expression of the angiogenic macrophage migration inhibitory factor (MIF), and the dense vascularization intimate a functional relationship. The proliferation index (Nv) was computed to be 1.6% in line with the balance of galectin expression. Abnormal p53 was expressed in only 19.4% of the cases. The diagnosis of LFT can be aided by quantitative assessment of vimentin, CD34, MIF, vascularization, and proliferation. Considering the galectin network, differential expression was noted with preference to effectors limiting growth and aggressiveness.}, } @article {pmid16288346, year = {2005}, author = {Meirelles, GS and Kavakama, JI and Jasinowodolinski, D and Nery, LE and Terra-Filho, M and Rodrigues, RT and Neder, JA and Bagatin, E and D'ippolito, G}, title = {[Asbestos-related pleuropulmonary diseases: pictorial essay].}, journal = {Revista portuguesa de pneumologia}, volume = {11}, number = {5}, pages = {477-485}, doi = {10.1016/s0873-2159(15)30519-5}, pmid = {16288346}, issn = {0873-2159}, mesh = {Asbestos/*adverse effects ; Asbestosis/*diagnostic imaging ; Humans ; Pleural Diseases/*diagnostic imaging/*etiology ; Radiography ; }, abstract = {Pleural and pulmonary asbestos-related diseases range from benign conditions, like pleural effusion and pleural plaques, to some neoplasias, such as lung cancer and malignant mesothelioma. Pleural effusion is the earliest finding after asbestos exposure, but the imaging findings are not specific. Diffuse pleural thickening involves the visceral pleura and pleural plaques are considered to be hallmarks of exposure. Asbestosis is the pulmonary fibrosis due to asbestos. Rounded atelectasis is a peripheral lung collapse in these individuals, generally related to pleural disease. Some neoplasias, like lung carcinoma and pleural mesothelioma, are more prevalent in asbestos-exposed subjects. The aim of this essay is to illustrate the main imaging findings of asbestos-related diseases.}, } @article {pmid16285225, year = {2005}, author = {Antman, K and Hassan, R and Eisner, M and Ries, LA and Edwards, BK}, title = {Update on malignant mesothelioma.}, journal = {Oncology (Williston Park, N.Y.)}, volume = {19}, number = {10}, pages = {1301-9; discussion 1309-10, 1313-6}, pmid = {16285225}, issn = {0890-9091}, mesh = {Antineoplastic Combined Chemotherapy Protocols/administration & dosage/*therapeutic use ; Asbestos/adverse effects ; Folic Acid Antagonists/administration & dosage/therapeutic use ; Heart Neoplasms/pathology ; Humans ; Incidence ; Male ; Mesothelioma/*diagnosis/*epidemiology/etiology/mortality/*pathology/*therapy ; Neoplasm Staging ; Peritoneal Neoplasms/pathology ; Platinum Compounds/administration & dosage/therapeutic use ; Pleural Neoplasms/pathology ; Prognosis ; Quality of Life/psychology ; Survival Analysis ; Testicular Neoplasms/pathology ; Treatment Outcome ; United States/epidemiology ; }, abstract = {Mesotheliomas are uncommon in the United States, with an incidence of about 3,000 new cases per year (or a risk of about 11 per million Americans per year). Incidence and mortality, however, are probably underestimated. Most are associated with asbestos, although some have arisen in ports of prior radiation, and a reported association with simian virus (SV)40 remains controversial. About 85% of mesotheliomas arise in the pleura, about 91% in the peritoneum, and a small percentage in the pericardium or tunica vaginalis testis. The histology of about half of mesotheliomas is epithelial (tubular papillary), with the remainder sarcomatous or mixed. Multicystic mesotheliomas and well-differentiated papillary mesotheliomas are associated with long survival in the absence of treatment and should be excluded from clinical trials intended for the usual rapidly lethal histologic variants of the disease. The median survival is under a year, although longer median survivals for selected patients, particularly those with epithelial histology, have been reported in some combined-modality studies. Recent randomized trials have shown significant improvement in time to progression and survival for the addition of new antifolates to platinum-based chemotherapy.}, } @article {pmid16273850, year = {2005}, author = {Canti, Z}, title = {[The national convention "asbestos-related pathology and health surveillance of those formerly exposed" --Pisa, 21-2 April, 2005 ].}, journal = {La Medicina del lavoro}, volume = {96}, number = {3}, pages = {270-271}, pmid = {16273850}, issn = {0025-7818}, mesh = {Air Pollutants, Occupational/adverse effects ; Asbestos/*adverse effects ; Carcinoma, Bronchogenic/epidemiology/etiology ; Cohort Studies ; *Environmental Exposure ; Follow-Up Studies ; Humans ; Lung Neoplasms/epidemiology/etiology ; Mesothelioma/epidemiology/etiology ; *Occupational Exposure ; Pleural Neoplasms/epidemiology/etiology ; *Population Surveillance ; Practice Guidelines as Topic ; }, } @article {pmid16273847, year = {2005}, author = {Carnevale, F}, title = {[Apropos of amianth and mesothelioma].}, journal = {La Medicina del lavoro}, volume = {96}, number = {3}, pages = {263-4; author reply 264-6}, pmid = {16273847}, issn = {0025-7818}, mesh = {Asbestos/*adverse effects ; Causality ; Humans ; Logic ; Mesothelioma/*etiology/prevention & control ; Mineral Fibers/adverse effects ; Particle Size ; Pleural Neoplasms/*etiology/prevention & control ; }, } @article {pmid16273846, year = {2005}, author = {Mollo, F}, title = {[Asbestos fiber dimensions and mesothelioma].}, journal = {La Medicina del lavoro}, volume = {96}, number = {3}, pages = {262; author reply 264-6}, pmid = {16273846}, issn = {0025-7818}, mesh = {Asbestos/*adverse effects/analysis ; Humans ; Mesothelioma/chemistry/*etiology ; Mineral Fibers/adverse effects/analysis ; Particle Size ; Pleura/chemistry ; Pleural Neoplasms/*etiology/prevention & control ; }, } @article {pmid16273844, year = {2005}, author = {Chiappino, G and Pellissetti, D and Moretto, O and Picchi, O}, title = {[Asbestos risk in the textile industry: braking systems on machinery used until the 1990's].}, journal = {La Medicina del lavoro}, volume = {96}, number = {3}, pages = {250-257}, pmid = {16273844}, issn = {0025-7818}, mesh = {Air Pollutants, Occupational/*adverse effects ; Air Pollution, Indoor ; Asbestos/*adverse effects ; Dust ; Equipment Contamination ; Equipment Design/*trends ; Humans ; Mesothelioma/etiology/prevention & control ; *Occupational Exposure ; Pleural Neoplasms/etiology/prevention & control ; Textile Industry/*instrumentation ; }, abstract = {BACKGROUND: We recently described asbestos risk in the non-asbestos textile industry as the result of fibre dispersion from ceilings, pipe insulation and machines.

OBJECTIVES: The widespread use of brakes with asbestos linings on the machines as well as other functional details were considered for a proper evaluation of their role in producing atmospheric pollution

METHODS: All the information was collected on the basis of the personal technical experience of two of the Authors and by direct observation of the machines.

RESULTS: All the textile machines (ring spinning, twisting, warping, winding, looms) used until the 1990's were without exception equipped with asbestos-lined mechanical brakes. The heavy action required produced relatively rapid wear of the linings and the dust produced was spread into the atmosphere by the continuous action of the "travelling blowing cleaners" and by the daily cleaning of the machines using compressed air at the end of the shift: violent air blowing undoubtedly caused redispersion of the fine dust from the brakes and also acted as a mechanical grinder on the bundles that sedimented on the machines from the ceilings and pipes, producing more ultrathin respirable fibres.

CONCLUSIONS: the contribution of textile machinery to atmospheric pollution by asbestos fibres was significant and due both to the widespread use of brakes with asbestos-containing materials and to the continuous action on the machines of compressed air blowers. Asbestos pollution was certainly high in all the factories so that in the near future still further mesothelioma cases among ex-workers are to be expected.}, } @article {pmid16273843, year = {2005}, author = {Fedi, A and Blagini, B and Melosi, A and Marzuoli, E and Ancillotti, M and Gorini, G and Costantini, AS and Silvestri, S and Innocenti, A}, title = {[Assessment of asbestos exposure, mortality study, and health intervention in workers formerly exposed to asbestos in a small factory making drying machines for textile finishing and the paper mill industry in Pistoia, Italy].}, journal = {La Medicina del lavoro}, volume = {96}, number = {3}, pages = {243-249}, pmid = {16273843}, issn = {0025-7818}, mesh = {Acquired Immunodeficiency Syndrome/mortality ; Adult ; Aged ; Air Pollutants, Occupational/adverse effects/*analysis ; Asbestos/*analysis ; Asbestos, Amosite/analysis ; Asbestos, Crocidolite/analysis ; Asbestos, Serpentine/analysis ; Cardiovascular Diseases/mortality ; Cause of Death ; Cohort Studies ; Dust/analysis ; Equipment Contamination/statistics & numerical data ; Follow-Up Studies ; Humans ; Italy ; Lung Neoplasms/etiology/mortality ; Male ; *Manufactured Materials ; Mesothelioma/etiology/mortality ; Mineral Fibers/analysis ; Neoplasms/mortality ; Occupational Diseases/etiology/*mortality ; *Occupational Exposure/statistics & numerical data ; Occupational Health Services/organization & administration/statistics & numerical data ; Paper ; Pleural Neoplasms/etiology/mortality ; Pulmonary Disease, Chronic Obstructive/etiology ; Textile Industry/*instrumentation ; Violence ; Workplace ; X-Ray Diffraction ; }, abstract = {BACKGROUND AND OBJECTIVES: Three malignant pleural mesotheliomas occurred among workers of a small factory that manufactured drying machines for the textile and paper mill industries using asbestos cement (crocidolite, amosite and chrysotile) as insulating panels. The Occupational Medicine Unit of the Local Health Unit of Pistoia, Italy, carried out an intervention programme in the plant in order to 1) assess past asbestos exposure via analysis of the fibre content of samples from drying machines, and of dust samples collected in the factory. Information on the characteristics of occupational exposure was also collected; 2) investigate cancer mortality by means of a mortality study of the employees and, 3) carry out a health intervention programme in workers formally exposed to asbestos in the past.

METHODS: Samples from the drying machines and dust samples collected in the factory were analysed using X-ray diffractometric methods. Information on the characteristics of occupational exposure were collected by interviewing plant workers. Two-hundred and fifty employees who had worked in the factory between 1962 and 2000 were included in the mortality study. Follow-up was performed from 1962 to 2002. Health intervention in workers exposed to asbestos in the past involved general practitioners and occupational physicians (first level medical examinations); pneumologists and radiologists (second level medical examinations) of the local health unit.

RESULTS: Asbestos fibres were found both in samples from drying machines and in dust samples collected in the factory. Interviews with workers showed that asbestos exposure varied considerably. The SMR for mesothelioma and lung cancer in 234 male workers were 37.0 (95%CI: 4.47-130.0), and 1.29 (95%CI: 0.26-3.78), respectively, based on mortality rates for Tuscany region. Sixty-two workers underwent first level medical examinations; 57 second level examinations. Chronic obstructive lung disease was found in 3 workers; restrictive lung disease was found in 3 employees, one of whom had pleural plaques.

CONCLUSIONS: Further investigation is needed in order to identify unknown asbestos exposures in small metal engineering factories.}, } @article {pmid16268941, year = {2005}, author = {Price, B and Ware, A}, title = {Mesothelioma: risk apportionment among asbestos exposure sources.}, journal = {Risk analysis : an official publication of the Society for Risk Analysis}, volume = {25}, number = {4}, pages = {937-943}, doi = {10.1111/j.1539-6924.2005.00643.x}, pmid = {16268941}, issn = {0272-4332}, mesh = {Asbestos/*adverse effects ; Humans ; Male ; Mesothelioma/economics/epidemiology/*etiology ; Models, Statistical ; Occupational Exposure/economics/legislation & jurisprudence ; Risk Assessment ; United States/epidemiology ; United States Occupational Safety and Health Administration ; }, abstract = {The mesothelioma epidemic in the United States, which peaked during the 2000-2004 period, can be traced to high-level asbestos exposures experienced by males in occupational settings prior to the full recognition of the disease-causing potential of asbestos and the establishment of enforceable asbestos exposure limits by the Occupational Safety and Health Administration (OSHA) in 1971. Many individuals diagnosed with mesothelioma where asbestos has been identified as a contributing cause of the disease have filed claims seeking compensation from asbestos settlement trusts or through the court system. An individual with mesothelioma typically has been exposed to asbestos in more than one setting and from more than one asbestos product. Apportioning risk for mesothelioma among contributing factors is an ongoing problem faced by occupational disease compensation boards, juries, parties responsible for paying damages, and currently by the U.S. Senate in its efforts to formulate a bill establishing an asbestos settlement trust. In this article we address the following question: If an individual with mesothelioma where asbestos has been identified as a contributing cause were to be compensated for his or her disease, how should that compensation be apportioned among those responsible for the asbestos exposures? For the purposes of apportionment, we assume that asbestos is the only cause of mesothelioma and that every asbestos exposure contributes, albeit differentially, to the risk. We use an extension of the mesothelioma risk model initially proposed in the early 1980s to quantify the contribution to risk of each exposure as a percentage of the total risk. The percentage for each specific discrete asbestos exposure depends on the start and end dates, the intensity, and the asbestos fiber type for the exposure. We provide justification for the use of the mesothelioma risk model for apportioning risk and discuss how to assess uncertainty associated with its application.}, } @article {pmid16257868, year = {2005}, author = {Dodson, RF and Graef, R and Shepherd, S and O'Sullivan, M and Levin, J}, title = {Asbestos burden in cases of mesothelioma from individuals from various regions of the United States.}, journal = {Ultrastructural pathology}, volume = {29}, number = {5}, pages = {415-433}, doi = {10.1080/019131290945682}, pmid = {16257868}, issn = {0191-3123}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/adverse effects/*analysis ; Asbestos, Amosite/adverse effects/analysis ; Asbestos, Amphibole/adverse effects/analysis ; Body Burden ; Cohort Studies ; *Environmental Exposure/statistics & numerical data ; Female ; Humans ; Lung Neoplasms/*etiology/mortality/pathology ; Male ; Mesothelioma/*etiology/mortality/pathology ; Middle Aged ; *Occupational Exposure/statistics & numerical data ; United States ; }, abstract = {Mesothelioma is a rare tumor that is considered an asbestos marker disease. It occurs in individuals following a longer latency period from first exposure than other asbestos-related diseases. The tumor also occurs in individuals with a wide range of exposures, including individuals with lower level or secondary exposures. In the present study lung tissue from 54 individuals with a pathological diagnosis of mesothelioma was evaluated for ferruginous body and uncoated asbestos fiber content. The data were compared with an earlier study of mesothelioma cases from the northwestern United States. Tissue was prepared via a digestion procedure, with the collected digestate reviewed by light microscopy for quantification of asbestos bodies and analytical transmission electron microscopy for determination of uncoated fiber burden. Twenty-seven cases in the present study had over 1000 ferruginous bodies per gram of dry tissue. The data suggest that amosite provides a more likely stimulus for ferruginous coating than the other forms of asbestos. All individuals were found to have asbestos fibers in their lung tissue. Amosite was the most commonly found fiber, with anthophyllite being the second most commonly found type of asbestos. The finding of tremolite in the tissue most often was associated with the finding of anthophyllite. A limited number of asbestos fibers of each type would have been seen in the light microscope, with the least detected being chrysotile. The majority of all fiber types were found as short fibers (< 8 mum), although some longer fibers were represented in each type of asbestos. The majority of the individuals were found to have mixed types of asbestos in their lungs.}, } @article {pmid16251370, year = {2005}, author = {Nichols, L and Sorahan, T}, title = {Mortality of UK electricity generation and transmission workers, 1973-2002.}, journal = {Occupational medicine (Oxford, England)}, volume = {55}, number = {7}, pages = {541-548}, doi = {10.1093/occmed/kqi157}, pmid = {16251370}, issn = {0962-7480}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestosis/mortality ; Brain Neoplasms/mortality ; Breast Neoplasms, Male/mortality ; *Cause of Death ; Cohort Studies ; *Electricity ; Electromagnetic Fields ; England/epidemiology ; Female ; Humans ; Male ; Mesothelioma/mortality ; Middle Aged ; Occupational Diseases/mortality ; Occupational Exposure ; Pleural Neoplasms/mortality ; *Power Plants ; Wales/epidemiology ; }, abstract = {OBJECTIVE: To examine mortality from cancer and non-malignant causes among a large cohort of UK electricity generation and transmission workers.

METHODS: The mortality experienced by a cohort of 83,923 employees of the former Central Electricity Generating Board of England and Wales was investigated for the period 1973-2002. All employees had worked for at least 6 months with some employment between 1973 and 1982. Standardized mortality ratios (SMRs) were used to assess mortality in the total cohort and in three sub-cohorts: power station workers, substation and transmission workers and workers at non-operational locations. These classifications were based on the place of work of the first known job.

RESULTS: Overall mortality was significantly below that expected, based on national rates [males: observed (Obs) 18,773, expected (Exp) 22,497.9, SMR 83; females: Obs 1122, Exp 1424.9, SMR 79]. Statistically significant deficits of deaths were also found for most of the major disease groupings. However, significant excesses of deaths were found in male power station workers for cancer of the pleura (Obs 129, Exp 30.3, SMR 426) and in male workers from non-operational locations for cancer of the brain (Obs 55, Exp 36.0, SMR 153). There was also a non-significant excess of deaths from cancer of the breast in male power station workers (Obs 10, Exp 5.3, SMR 190).

CONCLUSIONS: Mortality was exceptionally low for most causes of death but late health effects from earlier asbestos exposure were still in evidence.}, } @article {pmid16243515, year = {2005}, author = {Gennaro, V and Ugolini, D and Viarengo, P and Benfatto, L and Bianchelli, M and Lazzarotto, A and Montanaro, F and Puntoni, R}, title = {Incidence of pleural mesothelioma in Liguria Region, Italy (1996-2002).}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {41}, number = {17}, pages = {2709-2714}, doi = {10.1016/j.ejca.2005.04.047}, pmid = {16243515}, issn = {0959-8049}, mesh = {Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Humans ; Incidence ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*epidemiology ; Registries ; Sex Distribution ; }, abstract = {In this study, incidence of pleural malignant mesothelioma (PMM) in the Liguria Region (Italy) (approximately 1.6 million inhabitants), in the presence of asbestos exposure was investigated. New PMM cases recorded by the Mesothelioma Registry of Liguria, from 1996 to 2002 and interviews reported on a standardised questionnaire were analysed according to demographical and etiological characteristics. Nine hundred and forty five PMM cases were recorded (757 males and 188 females); the age standardised (European population) incidence rates per 100,000 were 8.51 and 1.43, respectively. The rates among the four provinces ranged between 1.18 and 13.7 for males and 0.68 and 1.44 for females. The questionnaire was evaluated for 786 PMM cases (or next-of-kin). Higher incidence rates were reported in the provinces with larger industrial and harbour areas, including shipyards (construction and repair), dockyards, building activities, chemical and heavy industrial activities. Asbestos exposure was unlikely or unknown for 57.5% females and 15% males. A major role of environmental asbestos exposure in the etiology of PMM is hypothesised for females and for a minor proportion of males.}, } @article {pmid16242011, year = {2005}, author = {Gudur, LD and Munavvar, M and Walsham, A and Edwards, JM}, title = {Simultaneous non-Hodgkin's lymphoma and mesothelioma presenting as a collision tumour.}, journal = {Histopathology}, volume = {47}, number = {5}, pages = {546-548}, doi = {10.1111/j.1365-2559.2005.02150.x}, pmid = {16242011}, issn = {0309-0167}, mesh = {Asbestos/*adverse effects ; Diagnosis, Differential ; Diaphragm/pathology ; Humans ; Lymphoma, Non-Hodgkin/complications/*diagnosis/pathology ; Male ; Mesothelioma/complications/*diagnosis/pathology ; Middle Aged ; Pericardium/pathology ; Pleural Neoplasms/complications/diagnosis/pathology ; }, } @article {pmid16241098, year = {2005}, author = {Tagliabue, F and Vertemati, G and Confalonieri, G and Romelli, A and Terragni, S and Costa, M}, title = {Benign solitary fibrous tumour of the pleura: a clinical review and report of six cases.}, journal = {Chirurgia italiana}, volume = {57}, number = {5}, pages = {649-653}, pmid = {16241098}, issn = {0009-4773}, mesh = {Adult ; Aged ; Algorithms ; Biopsy, Needle ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Male ; Microscopy, Electron ; Middle Aged ; *Neoplasms, Fibrous Tissue/diagnosis/diagnostic imaging/pathology/surgery ; Pleura/pathology ; *Pleural Neoplasms/diagnosis/diagnostic imaging/pathology/surgery ; Radiography, Thoracic ; Terminology as Topic ; Thoracoscopy ; Thoracotomy ; Time Factors ; Tomography, X-Ray Computed ; }, abstract = {Primary tumours of the pleura are commonly divided into two major categories: diffuse and localised. Whereas the diffuse variant is known for its association with asbestos and its poor outcome, the localised one is rare and remains a subject of controversy. Electron microscopy and immunohistochemistry have recently demonstrated that these tumours are of mesenchymal rather than mesothelial origin, and therefore the term "localised mesothelioma" was abandoned. Such tumours are now called solitary fibrous tumours of the pleura (SFTP). The Authors describe a series of 6 cases of benign solitary fibrous tumours of the pleura, surgically treated over the period 1982-2000.}, } @article {pmid16240434, year = {2005}, author = {Wang, MT and Mak, CW and Tzeng, WS and Chen, JC and Chang, JM and Lin, CN}, title = {Malignant mesothelioma of the tunica vaginalis testis: unusual sonographic appearance.}, journal = {Journal of clinical ultrasound : JCU}, volume = {33}, number = {8}, pages = {418-420}, doi = {10.1002/jcu.20140}, pmid = {16240434}, issn = {0091-2751}, mesh = {Aged, 80 and over ; Humans ; Male ; Mesothelioma/*diagnostic imaging/pathology ; Testicular Neoplasms/*diagnostic imaging/pathology ; Ultrasonography ; }, abstract = {Malignant mesothelioma of the tunica vaginalis testis is a rare and aggressive neoplasm. It is similar to malignant mesothelioma of the peritoneum, usually associated with asbestos exposure. We present an unusual case in which the tumor was a mix of a hypoechoic solid nodule and a cystic component with low-level internal echoes.}, } @article {pmid16221786, year = {2005}, author = {Cullen, MR}, title = {Serum osteopontin levels--is it time to screen asbestos-exposed workers for pleural mesothelioma?.}, journal = {The New England journal of medicine}, volume = {353}, number = {15}, pages = {1617-1618}, doi = {10.1056/NEJMe058176}, pmid = {16221786}, issn = {1533-4406}, mesh = {*Asbestos/adverse effects ; Biomarkers/blood ; Diagnosis, Differential ; Humans ; Mesothelioma/blood/*diagnosis ; *Occupational Exposure ; Osteopontin ; Pleural Neoplasms/blood/*diagnosis ; Sialoglycoproteins/*blood ; }, } @article {pmid16221782, year = {2005}, author = {Robinson, BW and Lake, RA}, title = {Advances in malignant mesothelioma.}, journal = {The New England journal of medicine}, volume = {353}, number = {15}, pages = {1591-1603}, doi = {10.1056/NEJMra050152}, pmid = {16221782}, issn = {1533-4406}, mesh = {Asbestos/adverse effects ; Genetic Therapy ; Humans ; *Mesothelioma/diagnosis/epidemiology/etiology/therapy ; Neoplasm Invasiveness ; Neoplasm Staging ; Palliative Care ; Peritoneal Neoplasms/diagnosis/therapy ; *Pleural Neoplasms/diagnosis/epidemiology/etiology/therapy ; Prognosis ; }, } @article {pmid16221779, year = {2005}, author = {Pass, HI and Lott, D and Lonardo, F and Harbut, M and Liu, Z and Tang, N and Carbone, M and Webb, C and Wali, A}, title = {Asbestos exposure, pleural mesothelioma, and serum osteopontin levels.}, journal = {The New England journal of medicine}, volume = {353}, number = {15}, pages = {1564-1573}, doi = {10.1056/NEJMoa051185}, pmid = {16221779}, issn = {1533-4406}, mesh = {Aged ; Asbestos/*adverse effects ; Asbestosis/*blood ; Biomarkers/blood ; Female ; Humans ; Male ; Mesothelioma/*blood/diagnosis/mortality/surgery ; Middle Aged ; Neoplasm Staging ; *Occupational Exposure ; Osteopontin ; Pleural Neoplasms/*blood/diagnosis/mortality/surgery ; ROC Curve ; Regression Analysis ; Sialoglycoproteins/analysis/*blood ; Survival Analysis ; }, abstract = {BACKGROUND: We investigated the presence of osteopontin in pleural mesothelioma and determined serum osteopontin levels in three populations: subjects without cancer who were exposed to asbestos, subjects without cancer who were not exposed to asbestos, and patients with pleural mesothelioma who were exposed to asbestos.

METHODS: A group of 69 subjects with asbestos-related nonmalignant pulmonary disease were compared with 45 subjects without exposure to asbestos and 76 patients with surgically staged pleural mesothelioma. Tumor tissue was examined for osteopontin by immunohistochemical analysis, and serum osteopontin levels were measured by an enzyme-linked immunosorbent assay.

RESULTS: There were no significant differences in mean (+/-SE) serum osteopontin levels between age-matched subjects with exposure to asbestos and subjects without exposure to asbestos (30+/-3 ng per milliliter and 20+/-4 ng per milliliter, respectively; P=0.06). In the group with exposure to asbestos, elevated serum osteopontin levels were associated with pulmonary plaques and fibrosis (56+/-13 ng per milliliter) but not with normal radiographic findings (21+/-5 ng per milliliter), plaques alone (23+/-3 ng per milliliter), or fibrosis alone (32+/-7 ng per milliliter) (P=0.004). Serum osteopontin levels were significantly higher in the group with pleural mesothelioma than in the group with exposure to asbestos (133+/-10 ng per milliliter vs. 30+/-3 ng per milliliter, P<0.001). Immunohistochemical analysis revealed osteopontin staining of the tumor cells in 36 of 38 samples of pleural mesothelioma. An analysis of serum osteopontin levels comparing the receiver-operating-characteristic curve in the group exposed to asbestos with that of the group with mesothelioma had a sensitivity of 77.6 percent and a specificity of 85.5 percent at a cutoff value of 48.3 ng of osteopontin per milliliter. Subgroup analysis comparing patients with stage I mesothelioma with subjects with exposure to asbestos revealed a sensitivity of 84.6 percent and a specificity of 88.4 percent at a cutoff value of 62.4 ng of osteopontin per milliliter.

CONCLUSIONS: Serum osteopontin levels can be used to distinguish persons with exposure to asbestos who do not have cancer from those with exposure to asbestos who have pleural mesothelioma.}, } @article {pmid16216834, year = {2005}, author = {Goldberg, M and Luce, D}, title = {Can exposure to very low levels of asbestos induce pleural mesothelioma?.}, journal = {American journal of respiratory and critical care medicine}, volume = {172}, number = {8}, pages = {939-940}, doi = {10.1164/rccm.2507003}, pmid = {16216834}, issn = {1073-449X}, mesh = {Asbestos/*adverse effects ; *Carcinogens ; Environmental Exposure/*adverse effects ; Humans ; Mesothelioma/epidemiology/*etiology ; Pleural Neoplasms/epidemiology/*etiology ; Residence Characteristics ; Risk Factors ; Time Factors ; }, } @article {pmid16206657, year = {2005}, author = {Papi, M and Genestreti, G and Tassinari, D and Lorenzini, P and Serra, S and Ricci, M and Pasquini, E and Nicolini, M and Pasini, G and Tamburini, E and Fattori, PP and Ravaioli, A}, title = {Malignant pericardial mesothelioma. Report of two cases, review of the literature and differential diagnosis.}, journal = {Tumori}, volume = {91}, number = {3}, pages = {276-279}, doi = {10.1177/030089160509100315}, pmid = {16206657}, issn = {0300-8916}, mesh = {Adult ; Aged ; Diagnosis, Differential ; Heart Neoplasms/complications/diagnosis/*pathology ; Humans ; Male ; Mesothelioma/complications/diagnosis/*pathology ; Pericardium/*pathology ; Prognosis ; Survival ; }, abstract = {Malignant pericardial mesothelioma is an uncommon variety of a primary malignant cardio-pericardial tumor and it is a highly lethal and fortunately rare cardiac neoplasm. The presentation of pericardial mesothelioma is aspecific and pathologically mesothelioma is not the most common among primary tumors of the pericardium. It is characterized by atypical solid growth of mesothelium with formation of atypical cavities surrounded by fibrous stroma. Antemortem diagnosis is difficult and distant metastases are extremely rare. Radical surgery can be used to treat localized mesothelioma. The treatment for advanced primary pericardial mesothelioma is usually palliative because the tumor is resistant to radiotherapy and chemotherapy. The prognosis is unfavorable. The median survival from the onset of symptoms is six months. In this paper we report two cases of patients with primary mesothelioma of the pericardium without a definite history of asbestos exposure.}, } @article {pmid16199813, year = {2005}, author = {Tan, C and Treasure, T}, title = {Mesothelioma: time to take stock.}, journal = {Journal of the Royal Society of Medicine}, volume = {98}, number = {10}, pages = {455-458}, pmid = {16199813}, issn = {0141-0768}, mesh = {Asbestos/adverse effects ; Combined Modality Therapy ; Humans ; Mesothelioma/epidemiology/etiology/*therapy ; United Kingdom/epidemiology ; }, } @article {pmid16181321, year = {2005}, author = {Gupta, L and Elder, J}, title = {Lung squeeze: a helpful adjunct in diagnosis.}, journal = {Cytopathology : official journal of the British Society for Clinical Cytology}, volume = {16}, number = {5}, pages = {269-270}, doi = {10.1111/j.1365-2303.2005.00253.x}, pmid = {16181321}, issn = {0956-5507}, mesh = {Asbestos/adverse effects ; Humans ; Male ; Mesothelioma/chemically induced/*diagnosis/*pathology ; Middle Aged ; Pleural Neoplasms/chemically induced/*diagnosis/*pathology ; }, } @article {pmid16174663, year = {2005}, author = {Burns, C and Harrison, K and Jammer, B and Zuccarini, D and Lafrance, B}, title = {A cancer incidence and mortality study of Dow Chemical Canada Inc. manufacturing sites.}, journal = {Occupational medicine (Oxford, England)}, volume = {55}, number = {8}, pages = {618-624}, doi = {10.1093/occmed/kqi145}, pmid = {16174663}, issn = {0962-7480}, mesh = {Adult ; Asbestos/adverse effects ; Canada/epidemiology ; Cause of Death ; Chemical Industry/*statistics & numerical data ; Cohort Studies ; Female ; Follow-Up Studies ; Humans ; Incidence ; Male ; Middle Aged ; Neoplasms/chemically induced/epidemiology/*mortality ; Occupational Diseases/chemically induced/epidemiology/*mortality ; Occupational Exposure/*adverse effects ; }, abstract = {BACKGROUND: Previously, the mortality was reported in a cohort of male workers at an Ontario chemical plant.

AIMS: To expand the cohort and to investigate the mortality and cancer incidence risk among chemical manufacturing sites.

METHODS: We followed 5277 men and 1301 women from 1950 to 1999.

RESULTS: Employees experienced lower mortality and cancer incidence rates than the general population for several major causes of death, including heart disease, respiratory cancer and many other cancers. There were no cases of angiosarcoma of the liver. We observed a lower mortality rate of prostate cancer [standardized mortality ratio = 0.79, 95% confidence interval (CI) 0.43-1.32], but a higher incidence rate of prostate cancer [standardized incidence ratio (SIR) = 1.22, 95% CI 1.00-1.48]. Among the Sarnia employees, the incidence of pleural neoplasms was increased (5 observed versus 1.48 expected, SIR = 3.37, 95% CI 1.09-7.86). These cancers were included in the 12 deaths with malignant mesothelioma at Sarnia.

CONCLUSION: Consistent with the earlier report, lower mortality rates were observed for the major classifications of disease and malignant neoplasms. The higher incidence rates of prostate cancer are not readily explainable but may reflect increased screening among current employees and recent retirees. Past asbestos exposure prior to 1980 is probably a contributor to the deaths due to malignant mesothelioma but is not reflected in lung cancer mortality. We find little indication of any other increased rates of mortality or cancer within the overall workforce of these chemical plants.}, } @article {pmid16173575, year = {2005}, author = {Ruda, TA and Dutta, PK}, title = {Fenten chemistry of Fe(III)-exchanged zeolitic minerals treated with antioxidants.}, journal = {Environmental science & technology}, volume = {39}, number = {16}, pages = {6147-6152}, doi = {10.1021/es050336e}, pmid = {16173575}, issn = {0013-936X}, mesh = {Aluminum Silicates/*chemistry ; Asbestos/chemistry ; Hydrogen Peroxide/chemistry ; *Hydroxyl Radical ; Iron/*chemistry ; Lung Neoplasms/physiopathology ; Mesothelioma/physiopathology ; Oxidation-Reduction ; Pulmonary Fibrosis/physiopathology ; Zeolites/*chemistry ; }, abstract = {Respirable mineral fibers, such as asbestos, are known to cause pleural mesothelioma, pulmonary fibrosis, and bronchial carcinoma, often years after exposure. Erionite and mordenite, two mineral aluminosilicates (zeolites) with different toxicities, can be used as models to help understand asbestos toxicity. Erionite is carcinogenic, while mordenite is relatively benign. No iron is typically present in erionite or mordenite, but because of their ion-exchange properties they can acquire iron after inhalation. The iron is typically in the Fe(III) form and will need to be reduced prior to any Fenton activity. Lung lining fluid contains antioxidants, such as glutathione (GSH) and ascorbic acid (AA), which can reduce Fe(III) to Fe(II). In this study, we have compared the Fenton reactivity of Fe(III)-exchanged erionite and mordenite after treatment with antioxidants. The Fenton assay involved the reaction of hydroxyl radicals with dimethyl sulfoxide. Fenton reactivity was most marked with AA followed by GSH, and hydrogen peroxide also exhibited minor reactivity. Erionite generated an order of magnitude greater hydroxyl radicals than mordenite, normalized to the surface iron content, providing support for the hypothesis that the iron coordination at the mineral surface plays a significant role in bioactivity.}, } @article {pmid16169910, year = {2005}, author = {Reid, A and de Klerk, N and Ambrosini, G and Olsen, N and Pang, SC and Musk, AW}, title = {The additional risk of malignant mesothelioma in former workers and residents of Wittenoom with benign pleural disease or asbestosis.}, journal = {Occupational and environmental medicine}, volume = {62}, number = {10}, pages = {665-669}, pmid = {16169910}, issn = {1470-7926}, mesh = {Aged ; Asbestos/adverse effects ; Asbestosis/*complications/pathology ; Female ; Humans ; Lung Neoplasms/diagnostic imaging/*etiology ; Male ; Mesothelioma/diagnostic imaging/*etiology ; Middle Aged ; *Occupational Exposure ; Pleura/diagnostic imaging ; Pleural Diseases/*complications/diagnostic imaging ; Proportional Hazards Models ; Radiography ; Risk ; Western Australia ; }, abstract = {AIMS: To examine the hypothesis that people with benign pleural disease or asbestosis have an increased risk of malignant mesothelioma beyond that attributable to their degree of asbestos exposure.

METHODS: Former workers and residents of the crocidolite mining and milling town of Wittenoom are participating in a cancer prevention programme (n = 1988). The first plain chest radiograph taken at the time of recruitment into the cancer prevention programme was read for evidence of benign pleural disease and asbestosis, using the UICC classification. Crocidolite exposure of former workers was derived from employment records and records of dust measurements performed during the operation of the asbestos mine and mill between 1943 and 1966. Based on fibre counts, exposure for former residents was determined using duration of residence and period of residence (before and after a new mill was commissioned in 1957) and interpolation from periodic hygienic measures undertaken from personal monitors between 1966 and 1992. Cox proportional hazards modelling was used to relate benign pleural disease, asbestosis, asbestos exposure, and mesothelioma.

RESULTS: Between 1990 and 2002, there were 76 cases of mesothelioma (56 of the pleura and 20 of the peritoneum). Cases had more radiographic evidence of (all) benign pleural disease, pleural thickening, blunt/obliterated costophrenic angle, and asbestosis than non-cases. Adjusting for time since first exposure (log years), cumulative exposure (log f/ml-years), and age at the start of the programme, pleural thickening (OR = 3.1, 95% CI 1.2 to 7.6) and asbestosis (OR = 3.3, 95% CI 1.3 to 8.6) were associated with an increased risk of peritoneal mesothelioma. There was no increased risk for pleural mesothelioma.

CONCLUSION: The presence of benign pleural disease, in particular pleural thickening, and asbestosis appears to increase the risk of mesothelioma of the peritoneum, but not of the pleura beyond that attributable to indices of asbestos exposure in this cohort of subjects exposed to crocidolite.}, } @article {pmid16169909, year = {2005}, author = {Goldberg, M}, title = {Are lung and pleural benign asbestos induced diseases a preliminary step in the pathogenic process of mesothelioma and lung cancer development?.}, journal = {Occupational and environmental medicine}, volume = {62}, number = {10}, pages = {663-664}, doi = {10.1136/oem.2005.021865}, pmid = {16169909}, issn = {1470-7926}, mesh = {Asbestosis/*pathology ; Disease Progression ; Humans ; Lung Neoplasms/*pathology ; Mesothelioma/*pathology ; Pleural Diseases/*pathology ; }, } @article {pmid16166281, year = {2005}, author = {Altomare, DA and Vaslet, CA and Skele, KL and De Rienzo, A and Devarajan, K and Jhanwar, SC and McClatchey, AI and Kane, AB and Testa, JR}, title = {A mouse model recapitulating molecular features of human mesothelioma.}, journal = {Cancer research}, volume = {65}, number = {18}, pages = {8090-8095}, doi = {10.1158/0008-5472.CAN-05-2312}, pmid = {16166281}, issn = {0008-5472}, support = {R01 CA077429/CA/NCI NIH HHS/United States ; ES-03721/ES/NIEHS NIH HHS/United States ; R01 CA045745/CA/NCI NIH HHS/United States ; CA-45745/CA/NCI NIH HHS/United States ; CA77429/CA/NCI NIH HHS/United States ; P30 CA006927/CA/NCI NIH HHS/United States ; CA-06927/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Asbestos, Crocidolite ; Cocarcinogenesis ; *Disease Models, Animal ; Genes, Neurofibromatosis 2/physiology ; Genes, p53/genetics ; Genetic Predisposition to Disease ; Humans ; Mesothelioma/chemically induced/*genetics/pathology ; Mice ; Mice, Knockout ; Tumor Suppressor Protein p14ARF/genetics ; }, abstract = {Malignant mesothelioma has been linked to asbestos exposure and generally has a poor prognosis because it is often diagnosed in advanced stages and is refractory to conventional therapy. Human malignant mesotheliomas accumulate multiple somatic genetic alterations, including inactivation of the NF2 and CDKN2A/ARF tumor suppressor genes. To better understand the significance of NF2 inactivation in malignant mesothelioma and identify tumor suppressor gene alterations that cooperate with NF2 loss of function in malignant mesothelioma pathogenesis, we treated Nf2 (+/-) knockout mice with asbestos to induce malignant mesotheliomas. Asbestos-exposed Nf2 (+/-) mice exhibited markedly accelerated malignant mesothelioma tumor formation compared with asbestos-treated wild-type (WT) littermates. Loss of the WT Nf2 allele, leading to biallelic inactivation, was observed in all nine asbestos-induced malignant mesotheliomas from Nf2 (+/-) mice and in 50% of malignant mesotheliomas from asbestos-exposed WT mice. For a detailed comparison with the murine model, DNA analyses were also done on a series of human malignant mesothelioma samples. Remarkably, similar to human malignant mesotheliomas, tumors from Nf2 (+/-) mice showed frequent homologous deletions of the Cdkn2a/Arf locus and adjacent Cdkn2b tumor suppressor gene, as well as reciprocal inactivation of Tp53 in a subset of tumors that retained the Arf locus. As in the human disease counterpart, malignant mesotheliomas from the Nf2 (+/-) mice also showed frequent activation of Akt kinase, which plays a central role in tumorigenesis and therapeutic resistance. Thus, this murine model of environmental carcinogenesis faithfully recapitulates many of the molecular features of human malignant mesothelioma and has significant implications for the further characterization of malignant mesothelioma pathogenesis and preclinical testing of novel therapeutic modalities.}, } @article {pmid16163251, year = {2004}, author = {Manegold, C}, title = {Current therapies for mesothelioma [correction of glioblastoma].}, journal = {Clinical advances in hematology & oncology : H&O}, volume = {2}, number = {10}, pages = {648-649}, pmid = {16163251}, issn = {1543-0790}, mesh = {Antineoplastic Agents/*therapeutic use ; Asbestos/adverse effects ; Humans ; Mesothelioma/*drug therapy/etiology ; }, } @article {pmid16163037, year = {2005}, author = {Salgado, RA and Corthouts, R and Parizel, PM and Germonpré, P and Carp, L and Van Schil, P and Van Marck, E}, title = {Malignant pleural mesothelioma with heterologous osteoblastic elements: computed tomography, magnetic resonance, and positron emission tomography imaging characteristics of a rare tumor.}, journal = {Journal of computer assisted tomography}, volume = {29}, number = {5}, pages = {653-656}, doi = {10.1097/01.rct.0000174028.06600.53}, pmid = {16163037}, issn = {0363-8715}, mesh = {Contrast Media ; Diagnosis, Differential ; Female ; Fluorodeoxyglucose F18 ; Gadolinium DTPA ; Humans ; Magnetic Resonance Imaging ; Mesothelioma/*diagnosis/pathology ; Middle Aged ; Pleural Neoplasms/*diagnosis/pathology ; Positron-Emission Tomography ; Radiopharmaceuticals ; Tomography, X-Ray Computed ; }, abstract = {The imaging findings of a rare mixed type of malignant mesothelioma of the pleura with heterologous bone stroma in a patient without a previous history of asbestos exposure are reported. Imaging findings of this type of bone-forming pleural mesothelioma are scarcely reported in the literature, with only a few case reports describing findings on conventional radiography, computed tomography, and magnetic resonance imaging. To the best of our knowledge, no positron emission tomography imaging characteristics of this type of mesothelioma have been previously reported.}, } @article {pmid16153138, year = {2005}, author = {Radak, JT}, title = {The medical record on trial: was it mesothelioma or lung cancer ... or another frivolous lawsuit?.}, journal = {Geriatrics}, volume = {60}, number = {9}, pages = {9-10}, pmid = {16153138}, issn = {0016-867X}, mesh = {Asbestos/toxicity ; Expert Testimony/methods ; *Health Knowledge, Attitudes, Practice ; Humans ; *Liability, Legal ; Lung Neoplasms/*diagnosis/etiology ; Medical Records/*legislation & jurisprudence ; Mesothelioma/*diagnosis/etiology ; Occupational Diseases/diagnosis/etiology ; Smoking/adverse effects ; Terminology as Topic ; United States ; }, } @article {pmid16149874, year = {2005}, author = {Suster, S and Moran, C}, title = {Malignant mesothelioma: current status of histopathologic diagnosis and molecular profile.}, journal = {Expert review of molecular diagnostics}, volume = {5}, number = {5}, pages = {715-723}, doi = {10.1586/14737159.5.5.715}, pmid = {16149874}, issn = {1744-8352}, mesh = {Animals ; Biomarkers, Tumor ; Humans ; Immunohistochemistry ; Mesothelioma/*diagnosis/*metabolism/pathology/ultrastructure ; Microscopy, Electron ; *Molecular Diagnostic Techniques ; Neoplasm Metastasis/pathology ; }, abstract = {Malignant mesothelioma of the pleura is a relatively rare neoplasm that has been estimated to account for 20 deaths per million males per year in North America and Europe. A causative association has been well established with asbestos exposure. Paradoxically, the incidence of this tumor continues to rise despite public efforts to reduce, contain or eliminate exposure to asbestos fibers over the past few decades. Another paradoxical feature of the disease is that the majority of malignant mesotheliomas represent morphologically low-grade, well-differentiated neoplasms, yet they follow a relentlessly aggressive and virtually uniformly fatal outcome. For this reason, identification of clinical, morphologic, immunohistochemical or molecular genetic parameters is of extremely limited value for prognostication. Surprisingly, for a disease that currently has no known cure, one of the major problems still lies in establishing the correct diagnosis. Diagnosis acquires a particular relevance in light of the medicolegal ramifications of this disease, and diagnosis of malignant mesothelioma is still fraught with difficulties. Despite the advances in modern diagnostic techniques, no specific markers or morphologic features exist that are exclusive to these tumors. Herein, the current status of malignant mesothelioma diagnosis is reviewed, including the possible contributions of modern molecular techniques for their diagnosis.}, } @article {pmid16133524, year = {2006}, author = {Hasanoglu, HC and Yildirim, Z and Ermis, H and Kilic, T and Koksal, N}, title = {Lung cancer and mesothelioma in towns with environmental exposure to asbestos in Eastern Anatolia.}, journal = {International archives of occupational and environmental health}, volume = {79}, number = {1}, pages = {89-91}, pmid = {16133524}, issn = {0340-0131}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*poisoning ; *Environmental Exposure ; Female ; Humans ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Population Surveillance ; Retrospective Studies ; Turkey/epidemiology ; }, abstract = {OBJECTIVE: Our previous study demonstrated the presence of environmental tremolite and chrysotile asbestos fiber exposure in Hekimhan town in Malatya located in eastern Turkey. The aim of this study was to investigate whether environmental asbestos exposure increases the incidence of lung cancer and mesothelioma.

METHOD: One hundred and forty-nine patients with mesothelioma and lung cancer living in the center or in the towns of Malatya were retrospectively analyzed. The Incidences of lung cancer and mesothelioma were calculated.

RESULTS: The incidences of lung cancer and mesothelioma were 3.39/100,000 and 0.21/100,000, respectively, for the whole population of Malatya; while they were 8.23/100,000 and 1.45/100,000 in Hekimhan. The incidences were strikingly high (22.39/100,000 for lung cancer and 7.46/100,000 for mesothelioma) in Arguvan, another town in Malatya where an analysis for asbestos could not be performed. The overall incidence in Turkey was reported as 5.9/100,000 by the Health Ministry in 1994. The incidences of lung cancer were nearly 1.3-fold higher in Hekimhan and fourfold higher in Arguvan then in the general population of Turkey.

CONCLUSION: The incidences of mesothelioma and lung carcinoma in Hekimhan were higher than those of the general population in Turkey, suggesting a role of environmental asbestos exposure in lung cancer and mesothelioma.}, } @article {pmid16130966, year = {2005}, author = {Welch, LS and Acherman, YI and Haile, E and Sokas, RK and Sugarbaker, PH}, title = {Asbestos and peritoneal mesothelioma among college-educated men.}, journal = {International journal of occupational and environmental health}, volume = {11}, number = {3}, pages = {254-258}, doi = {10.1179/107735205800245975}, pmid = {16130966}, issn = {1077-3525}, mesh = {Asbestos/*toxicity ; Case-Control Studies ; District of Columbia/epidemiology ; *Educational Status ; Humans ; Male ; Mesothelioma/chemically induced/*epidemiology ; Middle Aged ; Peritoneal Neoplasms/chemically induced/*epidemiology ; Universities ; }, abstract = {The proportion of peritoneal mesotheliomas among all mesotheliomas has been decreasing, leading some to suggest that peritoneal mesothelioma occurs only after high levels of exposure to asbestos. To investigate the relationship between asbestos exposure and the development of peritoneal mesothelioma, a case-control study examined 40 cases of primary peritoneal mesothelioma from a single institution. This series differed from previous reports in that 75% of the cases and controls had attended college. Results show an odds ratio of 6.6 for asbestos exposure among this group of primary peritoneal mesothelioma cases with relatively slight asbestos exposures.}, } @article {pmid16130821, year = {2005}, author = {Riehemann, K and Schmitt, O and Ehlers, EM}, title = {The effects of thermochemotherapy using cyclophosphamide plus hyperthermia on the malignant pleural mesothelioma in vivo.}, journal = {Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft}, volume = {187}, number = {3}, pages = {215-223}, doi = {10.1016/j.aanat.2004.12.019}, pmid = {16130821}, issn = {0940-9602}, mesh = {Animals ; Antineoplastic Agents, Alkylating/therapeutic use ; Cell Line, Tumor ; Combined Modality Therapy ; Cyclophosphamide/*therapeutic use ; Female ; Humans ; *Hyperthermia, Induced ; Mesothelioma/pathology/*therapy/ultrastructure ; Mice ; Mice, Nude ; Pleural Neoplasms/pathology/*therapy/ultrastructure ; Transplantation, Heterologous ; }, abstract = {The human malignant pleural mesothelioma is related to the use of asbestos in the majority of cases. Though the use of asbestos has been prohibited since the 1990s, the incidence of pleural mesothelioma is still increasing because of a latency period of at least 20 years. This study investigated the benefit of single therapy with cyclophosphamide or hyperthermia or the combination of both on cells of a human pleural mesothelioma cell line, xenotransplanted subcutaneously in the paw of mice. A CONTROL group received the same volume of physiological saline. The oxygenation of tumours was measured, tumour growth was followed over 3 weeks, immunohistochemical studies and a light and electron microscopic evaluation were performed. Chemotherapy or hyperthermia alone was only temporarily effective. The greatest benefit was achieved using combined thermochemotherapy consisting of cyclophosphamide plus hyperthermia: 50% of this group had partial remissions, and 67% responded to this therapy. After 3 weeks tumours grew again. Superior effects could be achieved by performing additional cycles of chemotherapy or adding another drug or radiation for instance. This study shows promising results in the treatment of malignant pleural mesothelioma.}, } @article {pmid16126764, year = {2006}, author = {Darnton, AJ and McElvenny, DM and Hodgson, JT}, title = {Estimating the number of asbestos-related lung cancer deaths in Great Britain from 1980 to 2000.}, journal = {The Annals of occupational hygiene}, volume = {50}, number = {1}, pages = {29-38}, doi = {10.1093/annhyg/mei038}, pmid = {16126764}, issn = {0003-4878}, mesh = {Adolescent ; Adult ; Aged ; Asbestos/*toxicity ; Humans ; Life Style ; Lung Neoplasms/*etiology/*mortality ; Male ; Mesothelioma/etiology/mortality ; Middle Aged ; Occupational Exposure/*adverse effects ; *Occupations ; Pleural Neoplasms/etiology/mortality ; Proportional Hazards Models ; Smoking/adverse effects ; United Kingdom/epidemiology ; Work ; }, abstract = {INTRODUCTION: Inhalation of asbestos fibres is known to cause two main kinds of cancer-mesothelioma and lung cancer. While the vast majority of mesothelioma cases are generally accepted as being caused by asbestos, the proportion of asbestos-related lung cancers is less clear and cannot be determined directly because cases are not clinically distinguishable from those due to other causes. The aim of this study was to estimate the number of asbestos-related lung cancers among males by modelling their relative lung cancer mortality among occupations within Great Britain in terms of smoking habits, mesothelioma mortality (as an index of asbestos exposure) and occupation type (as a proxy for socio-economic factors).

METHODS: Proportional mortality ratios for lung cancer and mesothelioma for the 20-year period from 1980 to 2000 (excluding 1981) were calculated for occupational groups. Smoking indicators were developed from three General Household Surveys carried out during the 1980s and 1990s. Poisson regression models were used to estimate the number of asbestos-related lung cancers by estimating the number of lung cancer deaths in each occupation assuming no asbestos exposure and subtracting this from the actual predicted number of lung cancer deaths.

RESULTS: The effect of asbestos exposure in predicting lung cancer mortality was weak in comparison to smoking habits and occupation type. The proportion of current smokers in occupational groups and average age at which they started smoking were particularly important factors. Our estimate of the number of asbestos-related lung cancers was between two-thirds and one death for every mesothelioma death: equivalent to between 11 500 and 16 500 deaths during the time period studied.

CONCLUSIONS: Asbestos-related lung cancer is likely to have accounted for 2-3% of all lung cancer deaths among males in Great Britain over the last two decades of the 20th century. Asbestos-related lung cancers are likely to remain an important component of the total number of lung cancer deaths in the future as part of the legacy of past asbestos exposures in occupational settings.}, } @article {pmid16112146, year = {2005}, author = {Bhattacharya, K and Dopp, E and Kakkar, P and Jaffery, FN and Schiffmann, D and Jaurand, MC and Rahman, I and Rahman, Q}, title = {Biomarkers in risk assessment of asbestos exposure.}, journal = {Mutation research}, volume = {579}, number = {1-2}, pages = {6-21}, doi = {10.1016/j.mrfmmm.2005.02.022}, pmid = {16112146}, issn = {0027-5107}, mesh = {Asbestos/adverse effects/*toxicity ; *Biomarkers/analysis ; Cytogenetic Analysis/methods ; *Environmental Exposure ; Genetic Predisposition to Disease ; Humans ; *Occupational Exposure ; Reactive Oxygen Species/analysis ; Risk Assessment/methods ; }, abstract = {Developments in the field of molecular epidemiology and toxicology have given valuable tools for early detection of impending disease or toxic condition. Morbidity due to respiratory distress, which may be due to environmental and occupational exposure, has drawn attention of researchers worldwide. Among the occupational exposure to respiratory distress factors, fibers and particles have been found to be main culprits in causing diseases like asbestosis, pleural plaques, mesotheliomas and bronchogenic carcinomas. An early detection of the magnitude of exposure or its' effect using molecular end points is of growing importance. The early inflammatory responses like release of the inflammatory cells collected by non-invasive methods give an indication of the unwanted exposure and susceptibility to further complications. Since free radicals like O2-, OH, OOH, NO, NOO, etc. are involved in the progression of asbestos-related diseases and lead to cytogenetic changes, an evaluation of antioxidant states reducing equivalents like GSH and ROS generation can be a good biomarker. The cytogenetic end points like chromosomal aberration, micronucleus formation and sister chromatid exchange give indication of genetic damage, hence they are used as effective biomarkers. New techniques like fluorimetric analysis of DNA unwinding, alkaline elution test, fluorescent in situ hybridization and comet assay are powerful tools for early detection of initiation of disease process and may help in planning strategies for minimizing morbidity related to asbestos fiber exposure. The present review article covers in detail possible biomarkers for risk assessment of morbidity due to fibers/particles in exposed population.}, } @article {pmid16109823, year = {2005}, author = {Rapisarda, V and Rapisarda, G and Vico, GD and Gobbi, L and Loreto, C and Valentino, M}, title = {Monitoring of fluoro-edenite fibre pollution through the study of sheep lymph nodes as a model of a biological indicator.}, journal = {Occupational and environmental medicine}, volume = {62}, number = {9}, pages = {656}, doi = {10.1136/oem.2005.020727}, pmid = {16109823}, issn = {1470-7926}, mesh = {Animals ; Asbestos, Amphibole/*analysis ; Biomarkers, Tumor ; Environmental Exposure/adverse effects ; *Lymph Nodes ; Lymphatic Metastasis ; Mesothelioma/*diagnosis ; Models, Biological ; Pleural Neoplasms/*diagnosis ; Sheep ; }, } @article {pmid16108147, year = {2004}, author = {White, MJ}, title = {Asbestos and the future of mass torts.}, journal = {The journal of economic perspectives : a journal of the American Economic Association}, volume = {18}, number = {2}, pages = {183-204}, doi = {10.1257/0895330041371187}, pmid = {16108147}, issn = {0895-3309}, mesh = {Asbestos/*adverse effects/economics/history ; Asbestosis/*economics/etiology ; Bankruptcy ; Europe ; Forecasting ; History, 20th Century ; Humans ; Jurisprudence/history ; Liability, Legal ; Mesothelioma/etiology ; Occupational Exposure ; United States ; Workers' Compensation/legislation & jurisprudence/trends ; }, } @article {pmid16106740, year = {2004}, author = {Hassmanová, V}, title = {[Diseases caused by asbestos dust and the trend of their development in exposed workers in 1951-2003].}, journal = {Acta medica (Hradec Kralove). Supplementum}, volume = {47}, number = {2}, pages = {107-120}, pmid = {16106740}, issn = {1211-247X}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Asbestosis/*epidemiology ; Czech Republic/epidemiology ; Female ; Humans ; Lung Diseases/epidemiology/etiology ; Lung Neoplasms/*epidemiology/etiology ; Male ; Mesothelioma/epidemiology/etiology ; Middle Aged ; *Occupational Exposure ; Pleural Neoplasms/epidemiology/etiology ; }, abstract = {The paper summarizes the principal information on the properties and effects of asbestos and a survey of diseases which can be recognized in the Czech Republic as occupational diseases according to the List of Occupational Diseases (Government Order 290/1995 Coll.). The paper lists possible diagnostic means and criteria for evaluation and presents a survey of developmental trends of the disease in exposed workers of the plant under study. In the period of years 1951-2003, 87 cases of occupational diseases were reported. The first asbestosis occurred in 1955, the first lung cancer in a patient with a previously reported asbestosis in 1962, the first pleural mesothelioma in 1976, the first asbestosis of the lung with concurrent lung cancer in 1981, and the first pleural hyalinosis in 1999. A very serious fact is that 56, i.e. 64.4% of diseases, particularly lung cancer and mesothelioma, were diagnosed after the termination of working in risk and many years of latency. A long-term folow-up of workers, even of those with a short exposure, is therefore necessary.}, } @article {pmid16103743, year = {2005}, author = {Filiberti, R and Marroni, P and Neri, M and Ardizzoni, A and Betta, PG and Cafferata, MA and Canessa, PA and Puntoni, R and Ivaldi, GP and Paganuzzi, M}, title = {Serum PDGF-AB in pleural mesothelioma.}, journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine}, volume = {26}, number = {5}, pages = {221-226}, doi = {10.1159/000087376}, pmid = {16103743}, issn = {1010-4283}, mesh = {Age Factors ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*blood ; Case-Control Studies ; Female ; Humans ; Lung Neoplasms/*pathology ; Male ; Mesothelioma/*pathology ; Middle Aged ; Platelet-Derived Growth Factor/*analysis ; Pleural Neoplasms/*pathology ; Prognosis ; Risk Factors ; Sex Factors ; Survival Analysis ; }, abstract = {Overexpression of platelet-derived growth factor (PDGF) has been observed in lung and pleural tumors. The aim of this study was to evaluate the diagnostic and prognostic role of serum PDGF in pleural mesothelioma (PM). Four groups of subjects were studied: 93 malignant PM patients, 33 primary non small cell lung cancer patients, 51 subjects exposed to asbestos, defined as high-risk controls, and 24 healthy controls. PDGF-AB mean concentration was higher in PM patients (45.8 ng/ml) than in high-risk controls (33.1 ng/ml) and healthy controls (26.8 ng/ml). Using the cut-off level of 49.8 ng/ml, corresponding to the mean+2SD of PDGF-AB in healthy controls, 43% of PM patients showed positive PDGF-AB levels. Survival was evaluated in 82 PM patients. At the end of the follow-up (median 9.8 months) 80.5% of patients had died. Median survival was 13.1 and 7.9 months for patients with PDGF-AB lower and higher than the cut-off, respectively. Adjusting for age, sex, histology and platelet count, positive PDGF-AB levels were associated with lower survival (OR=1.2, 95%CI: 0.9-1.6), even if not significantly so. In conclusion, serum PDGF may represent a useful additional parameter to prognostic factors already available for PM.}, } @article {pmid16093931, year = {2005}, author = {Nolan, RP and Ross, M and Nord, GL and Axten, CW and Osleeb, JP and Domnin, SG and Price, B and Wilson, R}, title = {Risk assessment for asbestos-related cancer from the 9/11 attack on the World Trade Center.}, journal = {Journal of occupational and environmental medicine}, volume = {47}, number = {8}, pages = {817-825}, doi = {10.1097/01.jom.0000167273.17109.6d}, pmid = {16093931}, issn = {1076-2752}, mesh = {Adolescent ; Adult ; Air Pollutants/adverse effects/*analysis ; Asbestos/*toxicity ; Child ; Child, Preschool ; Dust/analysis ; Environmental Exposure/adverse effects/*analysis ; Environmental Monitoring/methods ; Epidemiological Monitoring ; Female ; Humans ; Infant ; Lung Neoplasms/epidemiology/*etiology ; Male ; Mesothelioma/epidemiology/*etiology ; Middle Aged ; Models, Statistical ; New York City/epidemiology ; Risk Assessment/*methods ; *September 11 Terrorist Attacks ; United States ; United States Environmental Protection Agency ; }, abstract = {OBJECTIVE: We sought to estimate the lifetime risk of asbestos-related cancer for residents of Lower Manhattan attributable to asbestos released into the air by the 9/11 attack on New York City's World Trade Center (WTC).

METHODS: Exposure was estimated from available data and reasoned projections based on these data. Cancer risk was assessed using an asbestos risk model that differentiates asbestos fiber-types and the US Environmental Protection Agency's model that does not differentiate fiber-types and combines mesothelioma and lung cancer risks.

RESULTS: The upper limit for the expected number of asbestos-related cancers is less than one case over the lifetime of the population for the risk model that is specific for fiber-types and 12 asbestos-related cancers with the US Environmental Protection Agency's model.

CONCLUSIONS: The cancer risk associated with asbestos exposures for residents of Lower Manhattan resulting from the collapse of the WTC is negligible.}, } @article {pmid16075903, year = {2004}, author = {Luce, D and Billon-Galland, MA and Bugel, I and Goldberg, P and Salomon, C and Févotte, J and Goldberg, M}, title = {Assessment of environmental and domestic exposure to tremolite in New Caledonia.}, journal = {Archives of environmental health}, volume = {59}, number = {2}, pages = {91-100}, doi = {10.3200/AEOH.59.2.91-100}, pmid = {16075903}, issn = {0003-9896}, mesh = {Aged ; Air Pollution, Indoor/*analysis ; Asbestos, Amphibole/*analysis/standards ; Asbestos, Serpentine/analysis ; Bronchoalveolar Lavage Fluid/chemistry ; Cross-Sectional Studies ; Environmental Exposure/*analysis ; Female ; *Housing ; Humans ; Lung/chemistry ; Male ; Middle Aged ; New Caledonia ; }, abstract = {In this study, the authors characterized exposure to asbestos in the population of New Caledonia, an area where a high mesothelioma incidence was found to be associated with the use of a tremolite-containing whitewash on dwellings. The authors collected airborne samples from various sources. Lung tissue samples or bronchoalveolar lavage fluids were available for 80 subjects, who were interviewed regarding their residential and occupational histories. The authors analyzed all samples by analytical transmission electron microscopy. Results indicated that the use of the tremolite-based whitewash may generate high airborne fiber levels and result in asbestos lung contents comparable with those observed in occupational settings. The highest airborne tremolite concentrations were reached during sweeping in whitewashed houses. Lung concentrations of tremolite fibers were significantly higher in subjects exposed to the whitewash than in unexposed subjects, and the concentrations increased with the duration of exposure.}, } @article {pmid16054941, year = {2005}, author = {Robinson, BW and Musk, AW and Lake, RA}, title = {Malignant mesothelioma.}, journal = {Lancet (London, England)}, volume = {366}, number = {9483}, pages = {397-408}, doi = {10.1016/S0140-6736(05)67025-0}, pmid = {16054941}, issn = {1474-547X}, mesh = {Asbestos/adverse effects ; Humans ; *Mesothelioma/diagnosis/etiology/therapy ; *Peritoneal Neoplasms/diagnosis/etiology/therapy ; *Pleural Neoplasms/diagnosis/etiology/therapy ; }, abstract = {Malignant mesothelioma is an aggressive, treatment-resistant tumour, which is increasing in frequency throughout the world. Although the main risk factor is asbestos exposure, a virus, simian virus 40 (SV40), could have a role. Mesothelioma has an unusual molecular pathology with loss of tumour suppressor genes being the predominant pattern of lesions, especially the P16INK4A, and P14ARF, and NF2 genes, rather than the more common p53 and Rb tumour suppressor genes. Cytopathology of mesothelioma effusions or fine-needle aspirations are often sufficient to establish a diagnosis, but histopathology is also often required. Patients typically present with breathlessness and chest pain with pleural effusions. Median survival is now 12 months from diagnosis. Palliative chemotherapy is beneficial for mesothelioma patients with high performance status. The role of aggressive surgery remains controversial and growth factor receptor blockade is still unproven. Gene therapy and immunotherapy are used on an experimental basis only. Patterns identified from microarray studies could be useful for diagnosis as well as prognostication.}, } @article {pmid16051325, year = {2005}, author = {Picklesimer, AH and Zanagnolo, V and Niemann, TH and Eaton, LA and Copeland, LJ}, title = {Case report: malignant peritoneal mesothelioma in two siblings.}, journal = {Gynecologic oncology}, volume = {99}, number = {2}, pages = {512-516}, doi = {10.1016/j.ygyno.2005.06.033}, pmid = {16051325}, issn = {0090-8258}, mesh = {Adult ; Female ; Genetic Predisposition to Disease ; Humans ; Male ; Mesothelioma/*genetics ; Pedigree ; Peritoneal Neoplasms/*genetics ; Siblings ; }, abstract = {BACKGROUND: Mesothelioma is a rare tumor, linked with occupational asbestos exposure. This association has been used to explain clustering of cases within families. Newer evidence, however, supports a possible genetic predisposition for this tumor.

CASE: Our patient's brother was diagnosed with advanced stage malignant peritoneal mesothelioma in August 1995 at age of 42, he underwent tumor-reductive surgery followed by chemotherapy. He underwent a repeat cytoreductive surgery in September 1996 and further chemotherapy. He died of disease in December 1996. Our patient underwent cytoreductive surgery in May 1999 at age of 49 for advanced stage malignant peritoneal mesothelioma with suboptimal debulking. She received multiple chemotherapy regimens, including most recently experimental targeted agents, for slow progressing disease. She is presently alive with clinical disease 6 years from diagnosis.

CONCLUSION: This is the first report of two siblings of different gender with malignant peritoneal mesothelioma and only average environmental asbestos exposure. It is highly likely that the family described in this case report has some form of inherited susceptibility to malignancy cancer gene, HLA type, or tumor suppressor gene mutation.}, } @article {pmid16043260, year = {2005}, author = {Kokturk, N and Firat, P and Akay, H and Kadilar, C and Ozturk, C and Zorlu, F and Gungen, Y and Emri, S}, title = {Prognostic significance of Bax and Fas ligand in erionite and asbestos induced Turkish malignant pleural mesothelioma.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {50}, number = {2}, pages = {189-198}, doi = {10.1016/j.lungcan.2005.05.025}, pmid = {16043260}, issn = {0169-5002}, mesh = {Adenocarcinoma/etiology/genetics ; Adult ; Apoptosis/drug effects/*physiology ; Asbestos/poisoning ; Case-Control Studies ; Environmental Exposure ; Fas Ligand Protein ; Female ; Humans ; Immunohistochemistry ; Ligands ; Male ; Membrane Glycoproteins/analysis/*biosynthesis ; Mesothelioma/*etiology/*genetics ; Middle Aged ; Pleural Neoplasms/*etiology/*genetics ; Prognosis ; Survival Analysis ; Tumor Necrosis Factors/analysis/*biosynthesis ; Turkey ; Zeolites/poisoning ; bcl-2-Associated X Protein/metabolism/*physiology ; }, abstract = {Environmentally exposed erionite is a potent and unique inducer of malignant pleural mesothelioma (MPM) in Central Anatolia in Turkey. Previous studies have shown that erionite induced MPM has different biological behavior than asbestos induced MPM. Although impaired apoptosis has been implicated in tumor biology, the relationship between the type of environmental exposure and apoptosis has not yet been evaluated in MPM. The purpose of this study was to determine the expression of apoptosis regulating proteins and their prognostic significance in erionite and asbestos induced MPM. Thirty-five patients with MPM (16 erionite and 19 asbestos induced), and 17 patients with adenocarcinoma were comparatively evaluated. Expression of Bcl-2, Bax, Fas and Fas Ligand, were assessed by immunohistochemistry. Bcl-2 and Fas did not stain in almost all specimens. The staining extension of Bax was 13.75 +/- 19.27%, 5.89 +/- 14.51% and 7.38 +/- 14.53% for erionite and asbestos induced MPM and adenocarcinoma, respectively (p = 0.566). The staining extension of Fas Ligand was 26.87 +/- 31.87%, 46.10 +/- 37.30% and 26.47 +/- 23.23% for erionite and asbestos induced MPM, and adenocarcinoma, respectively (p = 0.123). Bax negative patients in erionite group had longer survival than Bax positive patients (18 months versus 14 months) (p = 0.06). Fas Ligand positive patients showed statistically better survival than Fas Ligand negative patients in all MPM group (15 months versus 12 months) (p = 0.05). Although all proteins expressed in similar extension in all samples, Bax staining displayed an inverse relation with survival in erionite group. This may implicate a difference in Bax functioning in erionite induced MPM. However, Fas Ligand may be functionally intact to reduce tumor survival.}, } @article {pmid16040098, year = {2005}, author = {Spiess, PE and Tuziak, T and Kassouf, W and Grossman, HB and Czerniak, B}, title = {Malignant mesothelioma of the tunica vaginalis.}, journal = {Urology}, volume = {66}, number = {2}, pages = {397-401}, doi = {10.1016/j.urology.2005.03.012}, pmid = {16040098}, issn = {1527-9995}, mesh = {Aged ; Aged, 80 and over ; Follow-Up Studies ; Humans ; Male ; Mesothelioma/*pathology/*surgery ; Middle Aged ; Retrospective Studies ; Testicular Neoplasms/*pathology/*surgery ; }, abstract = {OBJECTIVES: To review our experience with the management of malignant mesothelioma of the tunica vaginalis with emphasis on disease-related outcomes.

METHODS: A retrospective chart review of patients seen during the past 25 years at our cancer center identified 5 cases of malignant mesothelioma of the tunica vaginalis.

RESULTS: The mean age of patients at presentation was 61.2 years (range 57 to 83). Asbestos exposure was identified in 4 patients. Three patients presented with clinical symptoms suggestive of a hydrocele and two presented with clinical signs of an inguinal hernia. The final diagnosis was established intraoperatively in 1 patient and postoperatively in the remaining 4. Radical orchiectomy or hernia sac with spermatic cord excision was the primary treatment modality. Although radical surgical treatment achieved negative resection margins in 4 cases, 4 of 5 patients died of the disease, with a mean disease-specific survival of only 29 months (range 5 to 68). Regional inguinal lymph node metastasis developed in 3 of 5 patients. Salvage therapy did not prove curative in the 2 patients who received it.

CONCLUSIONS: Malignant mesothelioma of the tunica vaginalis constitutes a rare but often fatal malignancy of the male genitalia. This diagnosis should be suspected in patients exposed to asbestos and presenting with clinical symptoms of either hydrocele or inguinal hernia. Frequent inguinal lymph node involvement indicates a potential role of inguinal lymphadenectomy in the primary treatment.}, } @article {pmid16036750, year = {2004}, author = {Rödelsperger, K}, title = {Extrapolation of the carcinogenic potency of fibers from rats to humans.}, journal = {Inhalation toxicology}, volume = {16}, number = {11-12}, pages = {801-807}, doi = {10.1080/08958370490505016}, pmid = {16036750}, issn = {0895-8378}, mesh = {Animals ; Asbestos/toxicity ; Carcinogens/administration & dosage/pharmacokinetics/*toxicity ; Ceramics/toxicity ; Half-Life ; Humans ; Lung Neoplasms/chemically induced/pathology ; Mesothelioma/chemically induced/pathology ; Mineral Fibers/*toxicity ; Models, Statistical ; Rats ; Species Specificity ; }, abstract = {In 1999 Berry published a model for mesothelioma incidence following fiber exposure. He concluded, that the influence of the solubility of fibers on the mesothelioma rate is 17 times higher in humans than in rats. This conclusion may be helpful for evaluating the carcinogenic risk from man-made vitreous fibers, but it had little influence on some recent discussions. It has been demonstrated using this model, that in an injection experiment with rats, fibers with elimination constants of 0.1/year and 1/year--which would approximately correspond to crocidolite and perhaps ceramic fibers--differ in their mesothelioma risk only by a ratio of 3.2:1. In contrast, for humans exposed continuously from age 20 to age 60 a risk ratio of 4,750:1 is obtained. This result may be helpful for the assessment of the human cancer risk e.g., from exposure to refractory ceramic fibers. However, uncertainty is large, since the life-span of rats is too low to measure the elimination rate of bio-persistent fibers sufficiently.}, } @article {pmid16032742, year = {2005}, author = {Dave, SK and Beckett, WS}, title = {Occupational asbestos exposure and predictable asbestos-related diseases in India.}, journal = {American journal of industrial medicine}, volume = {48}, number = {2}, pages = {137-143}, doi = {10.1002/ajim.20198}, pmid = {16032742}, issn = {0271-3586}, mesh = {Asbestos, Serpentine/*toxicity ; Asbestosis/*epidemiology/etiology ; *Extraction and Processing Industry ; Forecasting ; Humans ; India/epidemiology ; Mesothelioma/epidemiology/etiology ; Occupational Diseases/*epidemiology/etiology ; Occupational Exposure/*adverse effects/analysis ; }, abstract = {BACKGROUND: India imports nearly 100,000 metric tons of asbestos per year, and small-scale asbestos (chrysotile and tremolite) mining and milling contributes nearly 5%-10% of the total national usage. The industry is relatively young, having started in the 1950s and 1960s.

METHODS: Surveys of asbestos-exposed workers have identified significant occupational exposures, early pleural and parenchymal changes on chest radiograph, and decrements in lung function.

RESULTS AND CONCLUSIONS: Based on knowledge of past and current exposures to asbestos in industry, we can predict a future occurrence of clinical asbestos-related diseases-pleural changes, pulmonary fibrosis, bronchogenic carcinoma, and diffuse malignant mesothelioma. These cases of asbestos related disease are expected to occur in asbestos exposed workers from mining, milling, and manufacturing as well as in those with secondary exposures to asbestos-containing materials, including construction and maintenance workers, users of asbestos-containing consumer products, and the occupants of asbestos-containing buildings.}, } @article {pmid16030111, year = {2005}, author = {Bolognesi, C and Martini, F and Tognon, M and Filiberti, R and Neri, M and Perrone, E and Landini, E and Canessa, PA and Ivaldi, GP and Betta, P and Mutti, L and Puntoni, R}, title = {A molecular epidemiology case control study on pleural malignant mesothelioma.}, journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology}, volume = {14}, number = {7}, pages = {1741-1746}, doi = {10.1158/1055-9965.EPI-04-0903}, pmid = {16030111}, issn = {1055-9965}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Case-Control Studies ; Female ; Humans ; Incidence ; Italy/epidemiology ; Lung Neoplasms/*genetics ; Male ; Mesothelioma/*etiology/genetics ; Micronucleus Tests ; Middle Aged ; *Molecular Epidemiology ; Occupational Exposure ; Pleural Neoplasms/*etiology/genetics ; Simian virus 40/genetics ; Smoking/*adverse effects/epidemiology ; }, abstract = {Pleural malignant mesothelioma is an uncommon neoplasm usually associated with asbestos exposure. The increasing incidence of malignant mesothelioma cases involving individuals with low levels of asbestos exposure suggests a complex carcinogenetic process with the involvement of other cofactors. Cytogenetic studies revealed the complexity of the genetic changes involved in this neoplasm reflecting the accumulation of genomic damage. One of the most used methodologies for assessing genomic damage is the cytokinesis-blocked micronucleus test applied in peripheral blood lymphocytes (PBL). This approach allows the detection of chromosomal alterations expressed in binucleated cells after nuclear division in vitro. This marker could provide a tool for assessing genetically determined constitutional differences in chromosomal instability. A biomonitoring study was carried out to evaluate the micronuclei frequency in PBLs of patients with pleural malignant mesothelioma with respect to lung cancer, healthy, and risk controls as a marker of cancer susceptibility in correlation with the presence of SV40. A significant increased micronuclei frequency was observed in patients with malignant mesothelioma in comparison with all the other groups, the mean micronuclei frequency was double in patients with malignant mesothelioma compared with healthy controls, risk controls, and patients with lung adenocarcinoma (median 11.4 binucleated cells with micronuclei/1,000 binucleated cells versus 6.2, 6.1, and 5.1, respectively). Our data indicate that human T lymphocyte samples carry DNA sequences coding for SV40 large T antigen at low prevalence, both in cancer cases and controls. Evidence of cytogenetic damage revealed as micronuclei frequency in mesothelioma cancer patients could be related to exogenous and endogenous cofactors besides asbestos exposure.}, } @article {pmid16021512, year = {2005}, author = {Ordóñez, NG}, title = {Clear cell mesothelioma presenting as an incarcerated abdominal hernia.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {447}, number = {5}, pages = {823-827}, pmid = {16021512}, issn = {0945-6317}, mesh = {Aged ; Biomarkers, Tumor/analysis ; Diagnosis, Differential ; Glycogen/analysis ; Hernia, Abdominal/*diagnosis/surgery ; Humans ; Immunoenzyme Techniques ; Male ; Mesothelioma/chemistry/*pathology/surgery ; Peritoneal Neoplasms/chemistry/*pathology/surgery ; }, abstract = {A clear cell mesothelioma presenting as an incarcerated ventral abdominal hernia in a 67-year-old man who had no history of asbestos exposure is described. The cause of the cytoplasmic clearing was the presence of large amounts of glycogen. Although uncommon, this variant of mesothelioma is important to recognize because it can be easily confused with other clear cell tumors involving the serosal membranes. Significant recent advances in the immunohistochemistry of epithelioid mesothelioma are briefly reviewed because immunohistochemical studies can be helpful in establishing the correct diagnosis.}, } @article {pmid16021506, year = {2005}, author = {Shia, J and Qin, J and Erlandson, RA and King, R and Illei, P and Nobrega, J and Yao, D and Klimstra, DS}, title = {Malignant mesothelioma with a pronounced myxoid stroma: a clinical and pathological evaluation of 19 cases.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {447}, number = {5}, pages = {828-834}, pmid = {16021506}, issn = {0945-6317}, mesh = {Adult ; Aged ; Biomarkers, Tumor/metabolism ; Female ; Humans ; Immunoenzyme Techniques ; Male ; Mesothelioma/metabolism/mortality/*pathology ; Middle Aged ; Mucus/metabolism ; Neoplasm Staging ; Pleural Neoplasms/metabolism/mortality/*pathology ; Stromal Cells/metabolism/pathology/ultrastructure ; Survival Rate ; }, abstract = {Mesothelioma with a pronounced myxoid stroma has been identified as a morphological pattern that might portend a better prognosis. Reports on this type of cases are few. Its clinical and pathological features are not defined. In this study, we identified 19 such cases from a series of 234 pleural mesotheliomas and performed a comprehensive clinical and pathological analysis. The inclusion criteria were mesotheliomas with at least 50% of the tumor exhibiting a pronounced myxoid stroma that occupied more than 50% of the tumor volume (designated as myxoid mesothelioma). There were ten males and nine females, with a median age of 58 years. Forty seven percent of the patients had probable or definite asbestos exposure. Patients presented at various stages [International Mesothelioma Interest Group (IMIG) stage II, 4; stage III, 9; and stage IV, 6]. Most (16/19) patients were treated by extrapleural pneumonectomy with adjuvant radiation or chemotherapy or both. Overall, the median survival rate was 36 months (median follow-up time, 17 months), and the 2-year survival rate was 79%. Histologically, the tumor cell component was entirely epithelioid without significant cytologic atypia. The myxoid material stained positive for Alcian blue, and the staining diminished after treatment with hyaluronidase in 12 of 12 cases. The tumor cells showed a typical mesothelial immunophenotype. Ultrastructurally, all six tumors examined had typical mesothelial-type surface microvilli and a moderately electron-dense extracellular amorphous material that often formed a haze enmeshing the surface microvilli. Hyaluronic acid-type, fern-like crystals were noted in all cases. These findings show that myxoid mesotheliomas represent a group of epithelioid mesotheliomas that have retained the secretory activity of normal mesothelium. Patients may present at different stages, but survival appears to be superior to that of epithelioid mesotheliomas in general. Our study emphasizes the need for better attention to histologic subtypes, particularly in the context of prognostically or therapeutically oriented investigations of this lethal disease.}, } @article {pmid16020040, year = {2005}, author = {Maxim, LD and McConnell, EE}, title = {A review of the toxicology and epidemiology of wollastonite.}, journal = {Inhalation toxicology}, volume = {17}, number = {9}, pages = {451-466}, doi = {10.1080/08958370591002030}, pmid = {16020040}, issn = {0895-8378}, mesh = {Animals ; Calcium Compounds/chemistry/*toxicity ; Drug Interactions ; Humans ; Inhalation Exposure ; Kinetics ; Legislation, Medical ; Neoplasms/chemically induced ; Occupational Exposure/legislation & jurisprudence/*statistics & numerical data ; Silicates/chemistry/*toxicity ; }, abstract = {Wollastonite is a naturally occurring calcium silicate (CaSiO(3)) that is produced in both powder and fibrous forms. It is a valuable industrial mineral used in plastics, ceramics, metallurgical applications, paint, and friction products. For some applications wollastonite serves as an asbestos replacement. To varying degrees, wollastonite grades contain respirable particles/fibers, some of which have lengths and diameters that might be biologically active if deposited and retained in the lung. In this review we provide background information on wollastonite properties, markets, production and use, regulatory classification, and occupational exposure limits. We also summarize the available studies on the toxicology and epidemiology of wollastonite. We conclude that there is inadequate evidence for the carcinogenicity of wollastonite in animals and, based on strong evidence that wollastonite is not biopersistent, believe that a well-designed animal inhalation bioassay would have a negative result. The epidemiological evidence for wollastonite is limited, but does not suggest that workers are at significant risk of an increased incidence of pulmonary fibrosis, lung cancer, or mesothelioma. Morbidity studies have demonstrated a nonspecific increase in bronchitis and reduced lung function. It is prudent, however, to continue product stewardship efforts by wollastonite producers to control workplace exposures and to monitor scientific developments.}, } @article {pmid16006571, year = {2005}, author = {Maruyama, R and Shoji, F and Okamoto, T and Miyamoto, T and Miyake, T and Nakamura, T and Ikeda, J and Aoki, Y and Wataya, H and Asoh, H and Ichinose, Y}, title = {Triplet chemotherapy with cisplatin, gemcitabine and vinorelbine for malignant pleural mesothelioma.}, journal = {Japanese journal of clinical oncology}, volume = {35}, number = {8}, pages = {433-438}, doi = {10.1093/jjco/hyi127}, pmid = {16006571}, issn = {0368-2811}, mesh = {Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Cisplatin/administration & dosage ; Combined Modality Therapy ; Deoxycytidine/administration & dosage/analogs & derivatives ; Drug Administration Schedule ; Female ; Humans ; Male ; Mesothelioma/*drug therapy/mortality/surgery ; Middle Aged ; Pleural Neoplasms/*drug therapy/mortality/surgery ; Pneumonectomy/methods ; Survival Rate ; Vinblastine/administration & dosage/analogs & derivatives ; Vinorelbine ; Gemcitabine ; }, abstract = {BACKGROUND: The incidence of malignant pleural mesothelioma (MPM) is expected to increase due to delayed control of occupational exposure to asbestos in Japan. We investigated the use of triplet combination chemotherapy with cisplatin (CDDP), gemcitabine (GEM) and vinorelbine (VNR) for the treatment of Japanese patients with MPM.

METHODS: From December 2000 to August 2003, 12 patients received the following regimen: CDDP 40 mg/m(2), GEM 800 mg/m(2) and VNR 20 mg/m(2) on days 1 and 8 every 4 weeks. Among the 12 patients, six selected patients underwent an extrapleural pneumonectomy (EP) after a median of three cycles of triplet chemotherapy.

RESULTS: The overall response rate for all patients and the response rate for chemotherapy-naive cases were 58 and 67%, respectively. The median survival time and survival rate at 2 years for all patients were 11 months and 50%, respectively. The 2-year survival rates for the patients with and without EP were 83.3 and 16.7%, respectively.

CONCLUSIONS: Triplet chemotherapy with CDDP, GEM and VNR was thus found to be highly effective for patients with MPM and its toxicity was manageable. A multi-institutional phase II trial is now being planned to establish the effectiveness of this new regimen in chemotherapy-naive patients with MPM.}, } @article {pmid16001518, year = {2005}, author = {Riboldi, L and Mensi, C and Canti, Z and Giordano, S and Chiappino, G}, title = {[Pleural malignant mesothelioma in a barber: a case of atypical and indirect professional exposure to asbestos].}, journal = {La Medicina del lavoro}, volume = {96}, number = {2}, pages = {177-178}, pmid = {16001518}, issn = {0025-7818}, mesh = {Air Pollutants/*adverse effects ; Air Pollutants, Occupational/*adverse effects ; Asbestosis/*complications ; *Barbering ; Chemical Industry ; Construction Materials/*adverse effects ; Dust ; Humans ; Italy ; Male ; Mesothelioma/*etiology ; Middle Aged ; *Occupational Exposure ; Pleural Neoplasms/*etiology ; Smoking Cessation ; }, } @article {pmid15999348, year = {2005}, author = {Bani-Hani, KE and Gharaibeh, KA}, title = {Malignant peritoneal mesothelioma.}, journal = {Journal of surgical oncology}, volume = {91}, number = {1}, pages = {17-25}, doi = {10.1002/jso.20266}, pmid = {15999348}, issn = {0022-4790}, mesh = {Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Asbestos/adverse effects ; Calbindin 2 ; Cisplatin/administration & dosage ; Combined Modality Therapy ; Diagnosis, Differential ; Diagnostic Errors/prevention & control ; Doxorubicin/administration & dosage ; Familial Mediterranean Fever/etiology ; Female ; Humans ; Immunohistochemistry ; Infusions, Parenteral ; Male ; Mesothelioma/*diagnosis/drug therapy/pathology/surgery ; Mesothelioma, Cystic/diagnosis/drug therapy/pathology/surgery ; Middle Aged ; Peritoneal Neoplasms/*diagnosis/drug therapy/pathology/surgery ; Prognosis ; Retrospective Studies ; S100 Calcium Binding Protein G/biosynthesis ; }, abstract = {BACKGROUND AND OBJECTIVES: The incidence of malignant peritoneal mesothelioma (MPM) is rising. Our aim was to present our experience with this entity in order to increase the awareness about this disease to avoid misdiagnosis.

METHODS: Records of seven patients with histologically confirmed MPM were retrospectively reviewed. Demographic and clinicopathological findings were studied in detail.

RESULTS: There were two females and 5 males; mean age was 50.3 years (range 16-73). Asbestos exposure was recorded in two patients, familial Mediterranean fever in one and previous radiation in one. Main presentations were abdominal pain and distension. None of the patients was diagnosed preoperatively. The average delay in diagnosis was 10 months. Calretinin expression was identified in all tumors. Three patients were treated with cytoreductive surgery combined with systemic chemotherapy. Two patients who remain alive were young female patients who were diagnosed by laparoscopic incidental findings and were treated with cytoreductive surgery combined with hyperthermic intraoperative intraperitoneal chemotherapy (HIIC). Median survival was 19.7 months. The average survival time of the five patients who died of their diseases was 10.2 months.

CONCLUSIONS: An awareness of MPM is important to prevent misdiagnosis. Immunohistochemistry has an important role in confirming the diagnosis. MPM remains a difficult therapeutic challenge. Thorough cytoreductive surgery is the cornerstone of current treatment while HIIC is a promising strategy in suitable patients.}, } @article {pmid15993904, year = {2005}, author = {Neri, M and Filiberti, R and Taioli, E and Garte, S and Paracchini, V and Bolognesi, C and Canessa, PA and Fontana, V and Ivaldi, GP and Verna, A and Bonassi, S and Puntoni, R}, title = {Pleural malignant mesothelioma, genetic susceptibility and asbestos exposure.}, journal = {Mutation research}, volume = {592}, number = {1-2}, pages = {36-44}, doi = {10.1016/j.mrfmmm.2005.06.003}, pmid = {15993904}, issn = {0027-5107}, mesh = {Asbestos/*adverse effects ; DNA/blood/genetics/isolation & purification ; Environmental Exposure ; *Genetic Predisposition to Disease ; Genotype ; Glutathione Transferase/genetics ; Humans ; Isoenzymes/genetics ; Mesothelioma/etiology/*genetics ; Micronucleus Tests ; Pleural Neoplasms/etiology/*genetics ; }, abstract = {Pleural malignant mesothelioma (MM) is a rare but extremely aggressive cancer. The limited impact of standard therapeutic treatments on survival rates makes the identification of factors that increase the individual risk a leading priority. The high proportion of cases explained by exposure to asbestos has guided intervention policies to an effective ban of this compound from our environment. However, MM cannot be solely attributed to this agent, and the role of predisposing factors and their interaction with asbestos exposure is increasingly studied. The role of mEH, GSTM1, GSTT1, NAT2, and CYP1A1 genotypes in modulating susceptibility to MM was examined in a case-control study of 80 subjects with a confirmed diagnosis of MM and 255 controls. Subjects with low mEH activity showed a significantly increased risk of MM (OR, 2.51; 95% CI, 1.11-5.68). The association was stronger in the group with low asbestos exposure (OR, 7.83; 95% CI, 0.98-62.60). A significant increased risk of MM was also found in NAT2 fast acetylators (OR, 1.74; 95% CI, 1.02-2.96). The presence of synergisms between genotypes, i.e., mEH and NAT2 (LRT for heterogeneity p<0.023), mEH and GSTM1 (LRT p<0.061), and NAT2 and GSTM1 (LRT p<0.049), combined with the interaction observed with exposure to asbestos, suggests the presence of gene-environment and gene-gene interactions in the development of MM, although the size of the study group does not allow to draw clearcut conclusions. Since genetic polymorphisms can also modify the extent of genetic damage occurring in subjects exposed to carcinogens, we measured the frequency of micronuclei in peripheral blood lymphocytes of a subgroup of MM cases. The limited number of cases (28) did not allow to observe significant effects. In conclusion, these results strengthen the hypothesis that individual susceptibility to MM can be modulated by the interaction between polymorphic genes involved in the metabolism and the intensity of asbestos exposure.}, } @article {pmid15991441, year = {2005}, author = {Janssen, JH}, title = {[Wonder matter and assassin. The perception of the asbestos danger as a mirror of the time 1930-1990].}, journal = {Gewina}, volume = {28}, number = {1}, pages = {38-53}, pmid = {15991441}, issn = {0928-303X}, mesh = {Asbestos/adverse effects/*history ; Asbestosis/history ; History, 20th Century ; Humans ; Lung Neoplasms/etiology/history ; Mesothelioma/etiology/history ; Netherlands ; Occupational Diseases/*history ; Occupational Health/history ; Protective Clothing/history ; Risk ; }, abstract = {In the seventies and eighties of the twentieth century the ideas of the dangers concerning the use of asbestos changed dramatically. The mineral, which had, more than half a century before been introduced in the Netherlands as a miraculous mineral, was completely banned from use. Asbestos became known as a 'silent killer' and 'the blue sand of death', and as a symbol of the hidden hazards of a deteriorating environment caused by unscrupulous companies and indolent authorities. Asbestos seems to fit perfectly into the ubiquitous hazards which Ulrich Beck defines in his concept of the 'risk society' as the dangerous side effects of industrial production. Yet the perception of the risk associated with asbestos depended more on socio-cultural characteristics than on scientifically risk assessments. In the first half of the twentieth century the use of asbestos was limited and therefore did not cause any concern. Economic crisis and war silenced the first alarming signals of asbestos related disease from foreign experts and a handful of Dutch physicians. The asbestos workers themselves were held responsible for their own health and safety. In the 1951 asbestosis became recognised as an industrial disease. Preventive measures with regard to the industrial use of asbestos were prescribed by law. Workers shared the responsibilities for a safe use with employers and authorities. However, during this period, all the attention was directed towards economic growth. Supervision by the labour inspection was scarce and workers and employers were not very interested in upholding the safety measures. Among asbestos workers the use of protective clothes and dust masks was generally seen as unmanly. In the sixties the foreign literature on the connection between the exposure to asbestos and the occurrence of lung cancer and mesothelioma became known among Dutch specialists. The results of these studies were confirmed by research among Dutch insulation workers. At the same time the trade unions rejected the idea of a shared responsibility and formulated the unilateral 'right to a safe working environment', with the implication that, in their view, all unhealthy and unsafe procedures should unconditionally be banned from the workshops, including the use of asbestos. Concerned civilians, environmental lobbyists, progressive political parties and concerned scientists transformed this idea into a 'right to a safe living environment', while mass media spread the message. Asbestos was pointed out as a threat to the public health, tracked down all of its hiding places and ultimately removed. The ban on asbestos was one of the results of democratisation and emancipation movement of the late sixties and seventies. The emancipation expressed itself in an increasing intolerance to risks brought about by powerful companies and bureaucratic authorities.}, } @article {pmid15976368, year = {2005}, author = {Pan, XL and Day, HW and Wang, W and Beckett, LA and Schenker, MB}, title = {Residential proximity to naturally occurring asbestos and mesothelioma risk in California.}, journal = {American journal of respiratory and critical care medicine}, volume = {172}, number = {8}, pages = {1019-1025}, pmid = {15976368}, issn = {1073-449X}, support = {1R03CA81615-01/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Age Distribution ; Aged ; Asbestos/*adverse effects ; California/epidemiology ; *Carcinogens ; Case-Control Studies ; Environmental Exposure/*adverse effects/analysis ; Female ; Geography ; Humans ; Incidence ; Logistic Models ; Male ; Mesothelioma/diagnosis/epidemiology/*etiology ; Middle Aged ; Multivariate Analysis ; Occupational Exposure/adverse effects/analysis ; Pancreatic Neoplasms/epidemiology/etiology ; Pleural Neoplasms/diagnosis/epidemiology/*etiology ; Registries ; Residence Characteristics ; Risk Factors ; Sex Distribution ; }, abstract = {RATIONALE: Little is known about environmental exposure to low levels of naturally occurring asbestos (NOA) and malignant mesothelioma (MM) risk.

OBJECTIVES: To conduct a cancer registry-based case control study of residential proximity to NOA with MM in California.

METHODS: Incident MM cases (n = 2,908) aged 35 yr or more, diagnosed between 1988 and 1997, were selected from the California Cancer Registry and frequency matched to control subjects with pancreatic cancer (n = 2,908) by 5-yr age group and sex. Control subjects were selected by stratified random sampling from 28,123 incident pancreatic cancers in the same time period. We located 93.7% of subjects at the house or street level at initial diagnosis. Individual occupational exposure to asbestos was derived from the longest held occupation, available for 74% of MM cases and 63% of pancreatic cancers. Occupational exposure to asbestos was determined by a priori classification and confirmed by association with mesothelioma.

MAIN RESULTS: The adjusted odds ratios and 95% confidence interval for low, medium, and high probabilities of occupational exposures to asbestos were 1.71 (1.32-2.21), 2.51 (1.91-3.30), and 14.94 (8.37-26.67), respectively. Logistic regression analysis from a subset of 1,133 mesothelioma cases and 890 control subjects with pancreatic cancer showed that the odds of mesothelioma decreased approximately 6.3% for every 10 km farther from the nearest asbestos source, an odds ratio of 0.937 (95% confidence interval = 0.895-0.982), adjusted for age, sex, and occupational exposure to asbestos.

CONCLUSIONS: These data support the hypothesis that residential proximity to NOA is significantly associated with increased risk of MM in California.}, } @article {pmid15971859, year = {2005}, author = {Suzuki, Y and Yuen, SR and Ashley, R}, title = {Short, thin asbestos fibers contribute to the development of human malignant mesothelioma: pathological evidence.}, journal = {International journal of hygiene and environmental health}, volume = {208}, number = {3}, pages = {201-210}, doi = {10.1016/j.ijheh.2005.01.015}, pmid = {15971859}, issn = {1438-4639}, mesh = {Animals ; Asbestos/*adverse effects ; Female ; Humans ; *Lung Neoplasms/etiology/pathology ; Male ; *Mesothelioma/etiology/pathology ; Mineral Fibers ; Particle Size ; }, abstract = {Based on animal studies, long and thin asbestos fibers (> or =8 microm in length and < or = 0.25 microm in width) have been postulated to be strongly carcinogenic inducing pleural malignant mesothelioma, while shorter, thicker fibers have been postulated to pose a lesser risk (Stanton hypothesis). The objective of this study is to test the validity of the Stanton hypothesis through direct pathologic analysis of human mesothelioma tissue. Digested bulk tissue samples, or ashed 25 microm thick sections, or both, were prepared from lung and mesothelial tissues taken from 168 cases of human malignant mesothelioma. In these tissues, 10,575 asbestos fibers (4820 in the lung and 5755 in mesothelial tissues (1259 in fibrotic serosa and 4496 in mesotheliomatous tissue)) were identified by high-resolution analytical electron microscopy. Dimensions of these asbestos fibers were measured in printed electron micrographs. Results were as follows: (1) long, thin asbestos fibers consistent with the Stanton hypothesis comprised only 2.3% of total fibers (247 / 10,575) in these tissues; (2) the majority (89.4%) of the fibers in the tissues examined were shorter than or equal to 5 microm in length (9454 of 10,575), and generally (92.7%) smaller than or equal to 0.25 microm in width (9808 of 10,575). (3) Among asbestos types detected in the lung and mesothelial tissues, chrysotile was the most common asbestos type to be categorized as short, thin asbestos fibers. (4) Compared with digestion technique of the bulk tissue, ashing technique of the tissue section was more effective to detect short, thin fibers. We conclude that contrary to the Stanton hypothesis, short, thin, asbestos fibers appear to contribute to the causation of human malignant mesothelioma. Such fibers were the predominant fiber type detected in lung and mesothelial tissues from human mesothelioma patients. These findings suggest that it is not prudent to take the position that short asbestos fibers convey little risk of disease.}, } @article {pmid15958571, year = {2005}, author = {Cacciotti, P and Barbone, D and Porta, C and Altomare, DA and Testa, JR and Mutti, L and Gaudino, G}, title = {SV40-dependent AKT activity drives mesothelial cell transformation after asbestos exposure.}, journal = {Cancer research}, volume = {65}, number = {12}, pages = {5256-5262}, doi = {10.1158/0008-5472.CAN-05-0127}, pmid = {15958571}, issn = {0008-5472}, support = {CA06927/CA/NCI NIH HHS/United States ; R01 CA077429/CA/NCI NIH HHS/United States ; R01 CA045745/CA/NCI NIH HHS/United States ; CA77429/CA/NCI NIH HHS/United States ; P30 CA006927/CA/NCI NIH HHS/United States ; CA45745/CA/NCI NIH HHS/United States ; }, mesh = {Apoptosis/physiology ; Asbestos/*toxicity ; *Cell Transformation, Viral ; Cocarcinogenesis ; Epithelial Cells/cytology/drug effects/enzymology/virology ; Humans ; Mesothelioma/enzymology/*etiology/pathology/virology ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphorylation ; Protein Serine-Threonine Kinases/*metabolism ; Proto-Oncogene Proteins/*metabolism ; Proto-Oncogene Proteins c-akt ; Simian virus 40/*physiology ; }, abstract = {Human malignant mesothelioma is an aggressive cancer generally associated with exposure to asbestos, although SV40 virus has been involved as a possible cofactor by a number of studies. Asbestos fibers induce cytotoxicity in human mesothelial cells (HMC), although cell survival activated by key signaling pathways may promote transformation. We and others previously reported that SV40 large T antigen induces autocrine loops in HMC and malignant mesothelioma cells, leading to activation of growth factor receptors. Now we show that SV40 induces cell survival via Akt activation in malignant mesothelioma and HMC cells exposed to asbestos. Consequently, prolonged exposure to asbestos fibers progressively induces transformation of SV40-positive HMC. As a model of SV40/asbestos cocarcinogenesis, we propose that malignant mesothelioma originates from a subpopulation of transformed stem cells and that Akt signaling is a novel therapeutic target to overcome malignant mesothelioma resistance to conventional therapies.}, } @article {pmid15955137, year = {2005}, author = {Sterman, DH and Albelda, SM}, title = {Advances in the diagnosis, evaluation, and management of malignant pleural mesothelioma.}, journal = {Respirology (Carlton, Vic.)}, volume = {10}, number = {3}, pages = {266-283}, doi = {10.1111/j.1440-1843.2005.00714.x}, pmid = {15955137}, issn = {1323-7799}, mesh = {Combined Modality Therapy ; Global Health ; Humans ; Incidence ; *Mesothelioma/diagnosis/epidemiology/therapy ; *Pleural Neoplasms/diagnosis/epidemiology/therapy ; Prognosis ; }, abstract = {Malignant mesothelioma is an insidious neoplasm arising from the mesothelial surfaces of the pleural and peritoneal cavities, the pericardium, or the tunica vaginalis. A total of 80% of all cases are pleural in origin. The predominant cause of malignant mesothelioma is inhalational exposure to asbestos, although evidence is increasing to support the hypothesis that simian virus-40 virus plays a role in cocarcinogenesis. Immunohistochemical markers such as calretinin, WT-1, and cytokeratin 5/6 are becoming established diagnostic markers. Preliminary data suggests that a soluble form of mesothelin could serve as a serum marker for established and early cases of mesothelioma. Positron emission tomography with 18-fluorodeoxyglucose in conjunction with computed tomograhy scanning has improved preoperative imaging and staging. Prognostic factors have been identified and verified. Negative indicators include thrombocytosis, high leukocyte counts, poor performance status, and nonepithelial histology. For the first time, there is now evidence that some treatments are increasing the quality and quantity of life for patients with mesothelioma. Chemotherapy, with the new multi-targeted antifolate drug Pemetrexed, combined with cisplatin, has shown superior survival rates in a large phase III trial when compared to cisplatin alone. High-dose intensity-modulated radiotherapy when administered after extrapleural pneumonectomy has resulted in excellent local control. Multimodality treatment programs that combine surgical cytoreduction with novel forms of radiation therapy and more effective chemotherapy combinations may offer significant increases in survival for certain subgroups of mesothelioma patients. Innovative palliative approaches have proved successful in alleviation of the significant symptoms experienced by many mesothelioma patients. Experimental treatments such as immunotherapy and gene therapy present a window of hope for all mesothelioma patients, and in the future, may be combined with 'standard therapy' in multimodality protocols. Patients with adequate performance status should be enrolled into clinical trials where possible. Over the past decade, significant advances have been made on several fronts that have improved the ability to diagnose a stage, define prognosis, and treat malignant pleural mesothelioma.}, } @article {pmid15950812, year = {2005}, author = {Gordon, GJ}, title = {Transcriptional profiling of mesothelioma using microarrays.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {49 Suppl 1}, number = {}, pages = {S99-S103}, doi = {10.1016/j.lungcan.2005.03.018}, pmid = {15950812}, issn = {0169-5002}, mesh = {Gene Expression Profiling ; Humans ; Mesothelioma/*genetics ; Oligonucleotide Array Sequence Analysis ; Pleural Neoplasms/*genetics ; }, abstract = {Mesothelioma is an asbestos-related neoplasm of the thoracic pleura about which little is known and for which effective therapy is lacking. Large-scale transcriptional profiling using microarrays is frequently a part of studies to explore gene expression patterns in cancer and other diseases. In general, microarray based experiments can facilitate the identification of tumor molecular markers, provide clues relating to mechanisms carcinogenesis, as well as aid in the discovery of candidate targets for therapy. Relatively few studies of this sort have been attempted for mesothelioma, likely due to its relatively rare incidence and by extension the difficulty in acquiring suitable tissues for analysis. Microarray analysis of mesothelioma will likely lead to a better understanding of a highly lethal malignancy and result in the identification of potential therapeutic targets to ultimately affect better treatment options and patient clinical outcome. This mini-review will address general issues pertaining to all expression profiling experiments (e.g., data interpretation) and summarize similar studies that have been attempted for mesothelioma.}, } @article {pmid15950797, year = {2005}, author = {Kazan-Allen, L}, title = {Asbestos and mesothelioma: worldwide trends.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {49 Suppl 1}, number = {}, pages = {S3-8}, doi = {10.1016/j.lungcan.2005.03.002}, pmid = {15950797}, issn = {0169-5002}, mesh = {Asbestos/*adverse effects ; Asbestosis ; Brazil ; Cost of Illness ; *Developed Countries ; *Developing Countries ; Environmental Exposure/adverse effects ; Humans ; India ; Kazakhstan ; Mesothelioma/*chemically induced ; Occupational Diseases/chemically induced ; Pleural Neoplasms/*chemically induced ; }, abstract = {A correlation between national asbestos consumption and the incidence of asbestos disease, including mesothelioma, has been observed. Towards the end of the 20th century, governments in many developed countries banned or seriously restricted the use of asbestos. As a result, global asbestos producers have engaged in aggressive marketing campaigns to sell asbestos to developing countries; consumption of white asbestos is increasing in Asia, Latin America and the Commonwealth of Independent States. In most of the countries, there is little, if any, control on hazardous asbestos exposures from occupational, environmental and domestic sources. It is likely that the lethal asbestos harvest which is occurring in the U.S., the UK and Australia will be reproduced in the developing world.}, } @article {pmid15950794, year = {2005}, author = {Gaafar, RM and Eldin, NH}, title = {Epidemic of mesothelioma in Egypt.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {49 Suppl 1}, number = {}, pages = {S17-20}, doi = {10.1016/j.lungcan.2005.03.025}, pmid = {15950794}, issn = {0169-5002}, mesh = {Adult ; Asbestos/*adverse effects ; *Disease Outbreaks ; Egypt/epidemiology ; Female ; Humans ; Male ; Mesothelioma/*epidemiology/genetics/pathology ; Pleural Neoplasms/*epidemiology/genetics/pathology ; }, abstract = {Asbestos has been recognized in Egypt since a long time as ancient Egyptians were using it in mummification. Mesothelioma in Egypt is mainly attributed to environmental origin with a high incidence of women and young adults affected. The incidence of mesothelioma is rising in Egypt. Epidemiological data for 635 malignant mesothelioma (MM) patients over 4 years in the third Millennium were collected from the National Cancer Institute (NCI), Cairo University and Abbassia Chest hospital. This number is more than four times the number diagnosed in the previous 11 years at NCI. A clinicopathological study was done for 100 malignant pleural mesothelioma (MPM) patients and showed that asbestos exposure and SV40 positivity were evident in 67% and 60% of cases, respectively. The median survival was 14.3 months and the 1 and 2 year survival rates were 60% and 27%, respectively. Evaluation of p53 and pRb immunohistochemically showed that pRb alteration was related to poor survival. Other biological prognostic factors such as EGFR, HER-2, glutathione S transferase (GST) and MDR were evaluated in 50 cases. Overexpression of EGFR was correlated with lack of clinical benefit and poor survival. GST potentiated the effect of EGFR on survival. The use of EGFR inhibitors may have a role in the treatment of MM. Asbestos in Cairo is a silent killer and measures toward eliminating it entirely or at least strictly controlling human contact with this dangerous carcinogen have to be taken in order to combat the coming epidemic of mesothelioma in Egypt.}, } @article {pmid15950793, year = {2005}, author = {Abratt, RP and White, NW and Vorobiof, DA}, title = {Epidemiology of mesothelioma--a South African perspective.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {49 Suppl 1}, number = {}, pages = {S13-5}, doi = {10.1016/j.lungcan.2005.03.004}, pmid = {15950793}, issn = {0169-5002}, mesh = {Asbestos/*adverse effects ; Humans ; Incidence ; Mesothelioma/*chemically induced ; Occupational Diseases/*chemically induced ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*chemically induced ; South Africa/epidemiology ; }, } @article {pmid15950789, year = {2005}, author = {Robinson, BW and Creaney, J and Lake, R and Nowak, A and Musk, AW and de Klerk, N and Winzell, P and Hellstrom, KE and Hellstrom, I}, title = {Soluble mesothelin-related protein--a blood test for mesothelioma.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {49 Suppl 1}, number = {}, pages = {S109-11}, doi = {10.1016/j.lungcan.2005.03.020}, pmid = {15950789}, issn = {0169-5002}, mesh = {Adult ; Asbestos/adverse effects ; Biomarkers, Tumor/*blood ; GPI-Linked Proteins ; Humans ; Lung Diseases/etiology/physiopathology ; Membrane Glycoproteins/*blood ; Mesothelin ; Mesothelioma/blood/*diagnosis ; Pleural Neoplasms/blood/*diagnosis ; }, abstract = {Identification of tumor marker for mesothelioma (MM) might prove useful in diagnosis as well as for monitoring tumor in response to therapy and for screening at-risk individuals. We tested the hypothesis that soluble mesothelin-related protein (SMRP), a mesothelin family member, in the serum would be such a marker. Our data show that determination of SMRP in serum is a marker of MM with a sensitivity of sensitivity 83% and specificity 95% in the first 48 MM patients tested. Changes in serum SMRP levels parallel clinical course/tumor size and SMRP is elevated in 75% of patients at diagnosis. SMRP should also be useful for monitoring disease progression, and importantly, may prove useful for screening asbestos-exposed individuals for early MM.}, } @article {pmid15948112, year = {2005}, author = {Ordóñez, NG}, title = {Mesothelioma with clear cell features: an ultrastructural and immunohistochemical study of 20 cases.}, journal = {Human pathology}, volume = {36}, number = {5}, pages = {465-473}, doi = {10.1016/j.humpath.2005.02.014}, pmid = {15948112}, issn = {0046-8177}, mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Immunohistochemistry ; Male ; Mesothelioma/metabolism/*pathology/*ultrastructure ; Microscopy, Electron, Transmission ; Middle Aged ; Peritoneal Neoplasms/metabolism/*pathology/*ultrastructure ; Pleural Neoplasms/metabolism/*pathology/*ultrastructure ; }, abstract = {Mesotheliomas with clear cell morphology are rare and only a few individual case reports have been documented in the literature. The author reports a series of 20 epithelioid mesotheliomas with clear features, 17 of which originated in the pleura and 3 in the peritoneum. Eighteen of the patients were men and 2 were women. Twelve patients had a history of asbestos exposure. Electron microscopy and special histochemical stains demonstrated that the cytoplasmic clearing seen in hematoxylin and eosin-stained sections resulted from multiple factors that can occur either singly or in combination. The most frequent cause of the cytoplasmic clearing was the accumulation of large amounts of intracytoplasmic glycogen. Another but somewhat less common factor was the accumulation of large amounts of lipid, which occurred alone or with glycogen. Other less common causes were marked mitochondrial swelling, the presence of numerous intracytoplasmic vesicles, and a large number of intracytoplasmic lumens. The value of immunohistochemistry in helping to distinguish epithelioid mesotheliomas from some carcinomas with clear cell morphology is emphasized. In addition, it was determined that because electron microscopy was decisive in establishing the cause of the cytoplasmic clearing in most of the cases, tissue for electron microscopy should routinely be procured for ultrastructural studies.}, } @article {pmid15941656, year = {2006}, author = {Chang, KC and Leung, CC and Tam, CM and Yu, WC and Hui, DS and Lam, WK}, title = {Malignant mesothelioma in Hong Kong.}, journal = {Respiratory medicine}, volume = {100}, number = {1}, pages = {75-82}, doi = {10.1016/j.rmed.2005.04.017}, pmid = {15941656}, issn = {0954-6111}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Cohort Studies ; Female ; Hong Kong/epidemiology ; Humans ; Incidence ; Male ; Mediastinal Neoplasms/*epidemiology/etiology ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Diseases/*epidemiology/etiology ; Occupational Exposure/statistics & numerical data ; Peritoneal Neoplasms/*epidemiology/etiology ; Pleural Neoplasms/*epidemiology/etiology ; }, abstract = {Malignant mesothelioma (mesothelioma) is rare. We conducted the first systematic study of the epidemiology of mesothelioma in Hong Kong from 1988 to May 2002 by reviewing medical records. Mesothelioma patients were identified from the database of 12 out of 20 hospitals that would have admitted mesothelioma patients territory-wide. These 12 hospitals served 73% of the total hospital bed-years of the 20 hospitals. We identified 67 mesothelioma patients. The estimated annual incidence was one per million, which was similar to the background incidence of one to two per million among Caucasians. Occupational history was available in 43 subjects. Three quarters of mesothelioma patients with available occupational history had occupational asbestos exposure. Restricting analysis to 48 patients with accessible medical records and using 67 occupational asbestosis patients for comparison, the epidemiology of mesothelioma in Hong Kong shares similarities with the literature: mean age of 63 years upon diagnosis, mean latency of 46 years, median survival of 9.5 months, male predominance, selective presentation among women, high prevalence among workers in ships and dockyards, predominantly epithelioid type, lower prevalence of asbestos bodies, and negative association with pleural plaques. Asbestos consumption in Hong Kong rose in the 1970s and peaked in early 1980s and late 1990s. Hong Kong may encounter an epidemic of mesothelioma in the 2010s if effective occupational asbestos control measures are not in place.}, } @article {pmid15933073, year = {2005}, author = {Rogers, A}, title = {Asbestos lung residue and asbestosis risk.}, journal = {The Annals of occupational hygiene}, volume = {49}, number = {4}, pages = {363-4; author reply 364-5}, doi = {10.1093/annhyg/mei005}, pmid = {15933073}, issn = {0003-4878}, mesh = {Asbestos/toxicity ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Mineral Fibers ; *Occupational Exposure ; Risk ; Time Factors ; }, } @article {pmid15920167, year = {2005}, author = {Gordon, GJ and Rockwell, GN and Jensen, RV and Rheinwald, JG and Glickman, JN and Aronson, JP and Pottorf, BJ and Nitz, MD and Richards, WG and Sugarbaker, DJ and Bueno, R}, title = {Identification of novel candidate oncogenes and tumor suppressors in malignant pleural mesothelioma using large-scale transcriptional profiling.}, journal = {The American journal of pathology}, volume = {166}, number = {6}, pages = {1827-1840}, pmid = {15920167}, issn = {0002-9440}, support = {R03 CA105249/CA/NCI NIH HHS/United States ; R33 CA100315/CA/NCI NIH HHS/United States ; CA-105249-02/CA/NCI NIH HHS/United States ; R21 CA100315/CA/NCI NIH HHS/United States ; CA-102591-01/CA/NCI NIH HHS/United States ; R21 CA098501/CA/NCI NIH HHS/United States ; CA-100315-01/CA/NCI NIH HHS/United States ; }, mesh = {Blotting, Western ; Cell Line, Tumor ; *Gene Expression Profiling ; *Genes, Tumor Suppressor ; Humans ; Immunohistochemistry ; Mesothelioma/*genetics ; Oligonucleotide Array Sequence Analysis ; *Oncogenes ; Pleural Neoplasms/*genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Transcription, Genetic ; }, abstract = {Malignant pleural mesothelioma (MPM) is a highly lethal, poorly understood neoplasm that is typically associated with asbestos exposure. We performed transcriptional profiling using high-density oligonucleotide microarrays containing approximately 22,000 genes to elucidate potential molecular and pathobiological pathways in MPM using discarded human MPM tumor specimens (n = 40), normal lung specimens (n = 4), normal pleura specimens (n = 5), and MPM and SV40-immortalized mesothelial cell lines (n = 5). In global expression analysis using unsupervised clustering techniques, we found two potential subclasses of mesothelioma that correlated loosely with tumor histology. We also identified sets of genes with expression levels that distinguish between multiple tumor subclasses, normal and tumor tissues, and tumors with different morphologies. Microarray gene expression data were confirmed using quantitative reverse transcriptase-polymerase chain reaction and protein analysis for three novel candidate oncogenes (NME2, CRI1, and PDGFC) and one candidate tumor suppressor (GSN). Finally, we used bioinformatics tools (ie, software) to create and explore complex physiological pathways. Combined, all of these data may advance our understanding of mesothelioma tumorigenesis, pathobiology, or both.}, } @article {pmid15916155, year = {2005}, author = {Lorusso, C and Merlicco, D and Giove, E and Palazzo, P and Nacchiero, M}, title = {[Chronic abdominal pain and peritoneal mesothelioma: case report].}, journal = {Chirurgia italiana}, volume = {57}, number = {2}, pages = {247-254}, pmid = {15916155}, issn = {0009-4773}, mesh = {Abdominal Pain/*etiology ; Aged ; Chronic Disease ; Humans ; Male ; Mesothelioma/*complications/surgery ; Peritoneal Neoplasms/*complications/surgery ; }, abstract = {Chronic abdominal pain syndrome is becoming increasingly important. The main symptom is persistent abdominal pain, which may vary intensely and be associated with constipation and episodes of vomiting, evolving towards sub- or total occlusion of the bowel. A 65-year old man presented with malignant peritoneal mesothelioma, with environmental asbestos exposure and chronic abdominal pain for more than one year. Due to his poor general condition, only palliative surgery was performed to resolve small and large bowel obstruction.}, } @article {pmid15915181, year = {2005}, author = {Abú-Shams, K and Boldú, J and Tiberio, G and Tabar, A and Fernández Infante, B and Labarta, N}, title = {[Registry of occupational respiratory diseases in Navarre].}, journal = {Anales del sistema sanitario de Navarra}, volume = {28 Suppl 1}, number = {}, pages = {135-143}, pmid = {15915181}, issn = {1137-6627}, mesh = {Adult ; Catchment Area, Health ; Female ; Humans ; Male ; Middle Aged ; Occupational Diseases/*epidemiology ; *Registries ; Respiratory Tract Diseases/*epidemiology ; Spain/epidemiology ; }, abstract = {BACKGROUND: In January 2002 an occupational respiratory diseases record was established in Navarre so that the number and characteristics of the occupational respiratory pathology could be analysed.

METHODS: The cases reported by doctors who collaborated in 2002, 2003 and 2004, were entered in a database for subsequently analysis. This database has several variables: gender, age, tobacco habit, hospital department and notifying doctor, diagnosis, job and causal agent.

RESULTS: 125 cases were reported. 97 males (77.6%) and 28 females (22.4%). Average age was 55,4 years old. Eighty-eight were non-smokers (70.4%) and 37 were smokers (29.6%). Pneumology reported 84 cases (67.2%) and Allergology 41 (32.8%). The diagnoses were: 50 bronchial asthma (40%), 31 benign pleural disease (24.8%), 8 extrinsic allergic alveolitis (6.4%), 8 mesothelioma (6.4%), 7 bronchopulmonary cancer (5.6%), 5 acute inhalations (4%), 3 amianthinopsy (2.4%), 2 rhinitis (1.6%), 1 RADS (0.8%) and 1 COPD (0.8%). The most reported jobs were: 13 painting and varnishing (10.4%), 12 spinning asbestos yarn (9.6%) and 8 bakery and confectionery (6.4%). The main causal agents were: 49 cases of asbestos (39.2%), 15 isocyanates (12%) and 8 silica (6.4%).

CONCLUSIONS: The most frequent pathology was bronchial asthma, followed by benign pleural disease. The most reported job was painting and varnishing and secondly spinning asbestos yarn. Asbestos was the first substance involved and the second was isocyanates. Most of the patients were males and non-smokers. The Pneumology Service of the Virgen del Camino Hospital reported most of the cases. Ratio contrast analysis showed a certain tendency towards a statistical significance in rhinitis, occupational asthma and amianthinopsy.}, } @article {pmid15915169, year = {2005}, author = {Fernández Infante, B and Michel, FJ}, title = {[Malign pleural mesothelioma].}, journal = {Anales del sistema sanitario de Navarra}, volume = {28 Suppl 1}, number = {}, pages = {29-35}, pmid = {15915169}, issn = {1137-6627}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Europe/epidemiology ; Female ; Humans ; Incidence ; Magnetic Resonance Imaging ; Male ; Mesothelioma/*diagnosis/*etiology ; Middle Aged ; Occupational Diseases/epidemiology ; Occupational Exposure/*adverse effects ; Pleura/blood supply/diagnostic imaging/pathology ; Pleural Neoplasms/*diagnosis/*etiology ; Positron-Emission Tomography ; Tomography, X-Ray Computed ; }, abstract = {Malign mesothelioma is a pleural neoplasia related to the occupational exposure to asbestos, although other factors can be involved; its incidence is increasing in Western Europe. Pain in the thorax and dyspnoea are its most frequent clinical manifestations. An important role in the evaluation of the disease is played by imaging techniques, of which CAT is the most widely used, although MR and PET are suggested as techniques that can provide additional information in the diagnosis and prognosis of these patients. Survival is short and there is no consensus in the literature that would orientate treatment of these patients. This is due to a lack of data that would confirm an increase of survival with any therapeutic method, although recent efforts have led to the development of new treatments that could change the present pessimistic view of the disease held by doctors and patients.}, } @article {pmid15915168, year = {2005}, author = {Boldú, J and Eguía, VM}, title = {[Benign pleural diseases induced by asbestos].}, journal = {Anales del sistema sanitario de Navarra}, volume = {28 Suppl 1}, number = {}, pages = {21-27}, pmid = {15915168}, issn = {1137-6627}, mesh = {Asbestos/*adverse effects ; Fibrosis/diagnostic imaging/*epidemiology/*etiology ; Humans ; Pleural Diseases/diagnostic imaging/*epidemiology/*etiology ; Pulmonary Atelectasis/diagnostic imaging/*epidemiology/*etiology ; Radiography, Thoracic ; Tomography, X-Ray Computed ; }, abstract = {Exposure to asbestos is an important cause of pleural pathology and can be produced with light or moderate tendencies given the capacity of asbestos to concentrate in the pleura. Together with the prolonged latency existing between exposure and the disease, this means that for many years we will continue to see pleural clinical manifestations from past exposure, in spite of the increasingly limited use of asbestos in recent decades. This exposure can show itself in different manifestations, both malign, such as mesothelioma, and benign, principally benign pleural effusion, pleural plaques, diffuse pleural fibrosis and massive atelectasis.}, } @article {pmid15901986, year = {2005}, author = {Gorini, G and De Gregorio, G and Silvestri, S and Chellini, E and Cupelli, V and Seniori Costantini, A}, title = {Survival of malignant pleural mesothelioma cases in the Tuscan Mesothelioma Register, 1988-2000: a population-based study.}, journal = {European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP)}, volume = {14}, number = {3}, pages = {195-199}, doi = {10.1097/00008469-200506000-00001}, pmid = {15901986}, issn = {0959-8278}, mesh = {Aged ; Female ; Humans ; Italy/epidemiology ; Male ; Mesothelioma/*mortality/pathology/therapy ; Middle Aged ; Multivariate Analysis ; Pleural Neoplasms/*mortality/pathology/therapy ; Prognosis ; Registries/*statistics & numerical data ; Survival Analysis ; }, abstract = {This study analyses survival of Tuscan residents (Italy, 3.5 million population) diagnosed by histological examination with malignant pleural mesothelioma (MPM) during the period 1988-2000, and recorded in the Tuscan Malignant Mesothelioma Register. The aim was to establish the prognostic role of demographic, diagnostic and asbestos exposure variables. During 1988-2000, 381 MPM cases were recorded (318 men; 63 women). Vital status was ascertained up to 31 December 2002. No cases were lost to follow-up. Median survival of certain MPM was 324 days (11 months; 95% CI 297-366); 45.7% (95% CI 40.6-50.6%) survived more than 1 year; 24.2% (95% CI 20.0-28.5%) more than 2 years. In univariate and multivariate analyses survival was associated with histological subtype (epithelioid subtype had the longest survival). Gender, age, period of diagnosis, hospital of diagnosis and asbestos exposure did not show significant effects. Therapeutic information was available for patients of the period 1997-2000. There was no significant difference in survival between treated versus untreated patients. In conclusion, no advance in prognosis at the population level in the most recent period can be suggested on the basis of the data available to the Tuscan Malignant Mesothelioma Register.}, } @article {pmid15897870, year = {2005}, author = {Altomare, DA and You, H and Xiao, GH and Ramos-Nino, ME and Skele, KL and De Rienzo, A and Jhanwar, SC and Mossman, BT and Kane, AB and Testa, JR}, title = {Human and mouse mesotheliomas exhibit elevated AKT/PKB activity, which can be targeted pharmacologically to inhibit tumor cell growth.}, journal = {Oncogene}, volume = {24}, number = {40}, pages = {6080-6089}, doi = {10.1038/sj.onc.1208744}, pmid = {15897870}, issn = {0950-9232}, support = {R01 CA077429/CA/NCI NIH HHS/United States ; ES-003721/ES/NIEHS NIH HHS/United States ; R01 CA045745/CA/NCI NIH HHS/United States ; CA-77429/CA/NCI NIH HHS/United States ; CA-45745/CA/NCI NIH HHS/United States ; P30 CA006927/CA/NCI NIH HHS/United States ; CA-06927/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Apoptosis ; Cell Proliferation/*drug effects ; Cell Survival ; Disease Models, Animal ; Enzyme Induction ; Gene Expression Profiling ; Humans ; Mesothelioma/*enzymology/*physiopathology ; Mice ; PTEN Phosphohydrolase ; Phosphoinositide-3 Kinase Inhibitors ; Phosphoric Monoester Hydrolases/physiology ; Phosphorylation ; Protein Kinases/drug effects ; Protein Serine-Threonine Kinases/antagonists & inhibitors/biosynthesis/*metabolism ; Proto-Oncogene Proteins/antagonists & inhibitors/biosynthesis/*metabolism ; Proto-Oncogene Proteins c-akt ; Signal Transduction ; TOR Serine-Threonine Kinases ; Tumor Cells, Cultured ; Tumor Suppressor Proteins/physiology ; }, abstract = {Malignant mesotheliomas (MMs) are very aggressive tumors that respond poorly to standard chemotherapeutic approaches. The phosphatidylinositol 3-kinase (PI3K)/AKT pathway has been implicated in tumor aggressiveness, in part by mediating cell survival and reducing sensitivity to chemotherapy. Using antibodies recognizing the phosphorylated/activated form of AKT kinases, we observed elevated phospho-AKT staining in 17 of 26 (65%) human MM specimens. In addition, AKT phosphorylation was consistently observed in MMs arising in asbestos-treated mice and in MM cell xenografts. Consistent with reports implicating hepatocyte growth factor (HGF)/Met receptor signaling in MM, all 14 human and murine MM cell lines had HGF-inducible AKT activity. One of nine human MM cell lines had elevated AKT activity under serum-starvation conditions, which was associated with a homozygous deletion of PTEN, the first reported in MM. Treatment of this cell line with the mTOR inhibitor rapamycin resulted in growth arrest in G1 phase. Treatment of MM cells with the PI3K inhibitor LY294002 in combination with cisplatin had greater efficacy in inhibiting cell proliferation and inducing apoptosis than either agent alone. Collectively, these data indicate that MMs frequently express elevated AKT activity, which may be targeted pharmacologically to enhance chemotherapeutic efficacy. These findings also suggest that mouse models of MM may be useful for future preclinical studies of pharmaceuticals targeting the PI3K/AKT pathway.}, } @article {pmid15895852, year = {2005}, author = {Fujiwara, H and Kamimori, T and Morinaga, K and Takeda, Y and Kohyama, N and Miki, Y and Inai, K and Yamamoto, S}, title = {An autopsy case of primary pericardial mesothelioma in arc cutter exposed to asbestos through talc pencils.}, journal = {Industrial health}, volume = {43}, number = {2}, pages = {346-350}, doi = {10.2486/indhealth.43.346}, pmid = {15895852}, issn = {0019-8366}, mesh = {Asbestos, Amphibole/*adverse effects ; *Dust ; Heart Neoplasms/*etiology/pathology ; Humans ; Male ; Mesothelioma/*etiology/pathology ; Middle Aged ; Occupational Exposure/*adverse effects ; *Pericardium ; Talc ; *Welding ; }, abstract = {An autopsy case of a primary pericardial mesothelioma in a 53-year-old arc cutter is reported. He had often had the chance to inhale dust generated by sharpening the slate pencils composed of talc. He was admitted for heart failure due to pericardial tumor, but later died. The tumor was mainly located on the pericardium with a thickness of about 2.5 cm. Small nodular disseminations were observed in the left parietal pleura. Microscopically, tumor cells were epithelial-like and rich in histochemical demonstrable hyaluronic acid. Findings of immunohistochemical markers revealed keratin (+), EMA (+), calretinin (+), and CEA (-), which were characteristics of mesothelioma of epithelial type. The number of asbestos bodies (AB) in the lung parenchyma was increased (2026 AB/gram dry lung tissue). Subsequent transmission electron microscopic examination equipped with an energy dispersive X-ray analyzer revealed that the fibers identified in the lungs were fibrous talc and actinolite. These findings suggested that this patient had been occupationally exposed to asbestos contaminated in the talc pencils, which induced the development of primary pericardial mesothelioma.}, } @article {pmid15894368, year = {2005}, author = {Hoekstra, AV and Riben, MW and Frumovitz, M and Liu, J and Ramirez, PT}, title = {Well-differentiated papillary mesothelioma of the peritoneum: a pathological analysis and review of the literature.}, journal = {Gynecologic oncology}, volume = {98}, number = {1}, pages = {161-167}, doi = {10.1016/j.ygyno.2005.03.031}, pmid = {15894368}, issn = {0090-8258}, mesh = {Aged ; Carcinoma, Papillary/*pathology ; Female ; Humans ; Mesothelioma/*pathology ; Peritoneal Neoplasms/*pathology ; }, abstract = {BACKGROUND: Well-differentiated papillary mesothelioma (WDPM) of the peritoneum is a rare subtype of peritoneal epithelioid mesothelioma which typically has low malignant potential. It most commonly occurs in young women lacking a history of asbestos exposure. Only 38 female patients with peritoneal WPDM have been reported in the literature, and no uniform treatment recommendation has been established.

CASE REPORT: A 74-year-old asymptomatic woman without significant past medical history underwent workup and subsequent surgery for an adnexal mass with a normal serum CA-125 level. Exploratory laparotomy identified an ovarian serous cystadenoma and an incidental multifocal peritoneal neoplasm with extensive calcifications. Histology and cytology confirmed WDPM with extensive, intimately associated mesothelial cystic inclusions and zonal calcifications with osseous metaplasia. Our patient did not receive adjuvant therapy and was without clinical or radiologic evidence of disease 12 months after diagnosis.

CONCLUSION: WDPM of the peritoneum in women is frequently asymptomatic and associated with an indolent course. Patient outcomes are usually favorable after tumor-debulking surgery without adjuvant therapy.}, } @article {pmid15893403, year = {2005}, author = {Gruber, UF}, title = {Mesothelioma, perspective from the industry.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {49 Suppl 1}, number = {}, pages = {S21-3}, doi = {10.1016/j.lungcan.2005.03.005}, pmid = {15893403}, issn = {0169-5002}, mesh = {Asbestos/*adverse effects ; Asbestosis/etiology ; Extraction and Processing Industry ; Humans ; Mesothelioma/*chemically induced ; *Occupational Exposure ; Pleural Neoplasms/*chemically induced ; Public Health/*standards ; Truth Disclosure ; }, } @article {pmid15864387, year = {2005}, author = {Gorini, G and Pinelli, M and Sforza, V and Simi, U and Rinnovati, A and Zocchi, G}, title = {Mesothelioma of the tunica vaginalis testis: report of 2 cases with asbestos occupational exposure.}, journal = {International journal of surgical pathology}, volume = {13}, number = {2}, pages = {211-214}, doi = {10.1177/106689690501300214}, pmid = {15864387}, issn = {1066-8969}, mesh = {Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Biomarkers, Tumor/analysis ; Humans ; Immunohistochemistry ; Male ; Mesothelioma/chemistry/etiology/*pathology ; Occupational Exposure/adverse effects ; Orchiectomy ; Testicular Neoplasms/chemistry/etiology/*pathology ; Testis/chemistry/*pathology/surgery ; Treatment Outcome ; }, abstract = {We report here 2 cases of malignant mesothelioma of the tunica vaginalis testis. A 67-year-old man with a left testicular mass was referred for left inguinal orchidectomy. Histologic examination showed a malignant mesothelioma of epithelial type. There is no evidence of recurrence at 2-year follow-up. The patient had been exposed to asbestos 12 years previously for a 30-year period. An 80-year-old man presented a 5-year history of scrotal swelling. Clinical examination revealed a hydrocele. The patient underwent resection of the tunica vaginalis through scrotal incision. Microscopic examination showed a malignant mesothelioma of biphasic type. There is no evidence of recurrence at 2-year follow-up. The patient had been exposed to asbestos 52 years previously for a 5-year period.}, } @article {pmid15859189, year = {2005}, author = {Comba, P and Merler, E and Pasetto, R}, title = {Asbestos-related diseases in Italy: epidemiologic evidences and public health issues.}, journal = {International journal of occupational and environmental health}, volume = {11}, number = {1}, pages = {36-44}, doi = {10.1179/oeh.2005.11.1.36}, pmid = {15859189}, issn = {1077-3525}, mesh = {Asbestos/*adverse effects ; Communication ; Emigration and Immigration ; Epidemiologic Studies ; Humans ; Italy/epidemiology ; Liability, Legal ; Mesothelioma/*epidemiology/*etiology ; *Occupational Exposure ; Population Surveillance ; *Public Health/legislation & jurisprudence ; Registries/*statistics & numerical data ; Risk Assessment ; Social Security ; }, abstract = {Epidemiologic information about asbestos-related diseases in Italy, derived from mortality data, epidemiologic surveillance, and analytical studies, is presented. These systems evidence exposures to asbestos and relative risks for populations exposed in work environments and also in the general environment, and provide objective data to identify sources of exposure and for risk management. Limitations and perspectives of Italian studies are considered, and public health issues evaluated: the risk for migrants, social security aspects, and asbestos-related disease in the courts. Although asbestos use was banned in 1992, information and risk communication efforts should be implemented to empower affected individuals and communities and to pursue equitable allocation of resources for primary prevention and health surveillance.}, } @article {pmid15849996, year = {2005}, author = {de Pangher Manzini, V}, title = {Malignant peritoneal mesothelioma.}, journal = {Tumori}, volume = {91}, number = {1}, pages = {1-5}, doi = {10.1177/030089160509100101}, pmid = {15849996}, issn = {0300-8916}, mesh = {Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Ascitic Fluid/pathology ; Carcinogens/adverse effects ; Environmental Exposure/adverse effects ; Female ; Humans ; Italy/epidemiology ; Laparoscopy ; Laparotomy ; Male ; *Mesothelioma/complications/diagnosis/epidemiology/etiology/surgery ; Middle Aged ; *Peritoneal Neoplasms/complications/diagnosis/epidemiology/etiology/surgery ; Thrombocytosis/etiology ; }, abstract = {BACKGROUND: The clinical characteristics of malignant peritoneal mesothelioma are not fully known, and it appears as a variable entity with different types of clinical presentation and with a difficult diagnosis.

PATIENTS: Fifteen patients with malignant peritoneal mesothelioma were analyzed for asbestos exposure, clinical presentation, thrombocytosis, X-rays and echotomographic findings, peritoneal fluid cytology, surgical investigations, diagnosis in vita, therapy, cause of death, diagnosis time, and survival time.

RESULTS: Asbestos exposure was present in 12 men. Abdominal pain, ascites, abdominal mass, weight loss and fever were the most common presentation symptoms. In 5 patients, the disease presented as a surgical emergency. Assembling the presenting symptoms, malignant peritoneal mesothelioma was subdivided in 3 types: classical (6 cases), surgical (5 cases) and medical (4 cases). Thrombocytosis was present in 11 cases. Peritoneal fluid cytology was positive for neoplastic mesothelial cells in 8 of 10 cases. Laparotomy (5 patients) and laparoscopy (7 cases) were diagnostic in all cases. Diagnosis in vita was malignant peritoneal mesothelioma for 13 patients, peritoneal carcinomatosis for 1, with only 1 autopsy diagnosis. Seven patients were treated with chemotherapy, showing a progression of the disease. Mean symptoms-to-diagnosis time was 122 days (4-410), and mean symptoms-to-survival time was 345 days (45-1510).

CONCLUSIONS: Malignant peritoneal mesothelioma is a very unusual disease characterized by a difficult diagnosis, a rapid evolution, a poor response to therapy, and a very high prevalence of thrombocytosis. A new clinical classification into three types (classical, surgical and medical) may be useful for a correct diagnosis. The early diagnosis of malignant peritoneal mesothelioma remains an important open question.}, } @article {pmid15847104, year = {2005}, author = {Chiappino, G}, title = {[Mesothelioma: the aetiological role of ultrathin fibres and repercussions on prevention and medical legal evaluation].}, journal = {La Medicina del lavoro}, volume = {96}, number = {1}, pages = {3-23}, pmid = {15847104}, issn = {0025-7818}, mesh = {Asbestos/adverse effects ; Humans ; Mesothelioma/*etiology/*prevention & control ; Microscopy, Electron ; Mineral Fibers/adverse effects ; Occupational Health/legislation & jurisprudence ; Particle Size ; Pleural Neoplasms/*etiology/*prevention & control ; }, abstract = {BACKGROUND: Mesothelioma has until now been considered to be a manifestation, occurring in the pleura and/or peritoneum, of the carcinogenic action of the total burden of inhaled asbestos fibres, in the same way as lung cancer. Because of the pathogenic potential of very low exposure levels, the fact that the onset of the neoplasm always occurs in the parietal pleura, and the absence of any synergism with smoking, which is typical in the case of carcinoma, it was suspected that aetiopathogenetic differences existed but the reasons for such differences still could not be explained. In the past experimental results indicated the oncogenicity of very thin fibres but mesothelioma in practice was not exclusively linked to this specific dimensional size class.

OBJECTIVES: The paper proposes to take full advantage of the significant knowledge that must emerged from research carried out in recent years and use this knowledge to reconstruct the mosaic of the aetiopathogenesis of mesothelioma. Due consideration will also be given to the consequent new approach required in the field of medical-legal evaluation of cases and in the field of prevention.

RESULTS: The most important knowledge that must today be taken as certain is the fact that mesothelioma is not caused, as is the case for asbestosis, by all the fibres that are inhaled but only by the ultrathin fraction of these fibres, having diameter of 0.2 microm and length of only a few microm. Only fibres of this class of size can cross the pulmonary-pleural barrier and are, therefore, the causal agent of mesothelioma and other benign pleural manifestations (plaques). Moreover the ultrathin fibres that translocate from the lung to the pleura are not distributed casually on the parietal and visceral surfaces but move over the surfaces, to concentrate around the lymphatic reabsorption stomata situated on the parietal pleura. Due to their shape, the fibres cannot easily be absorbed into the stoma via the lymphatic flow and so remain clustered for an indefinite period of time among the mesothelial cells that surround the stoma. The concentration of ultrathin fibres in punctiform areas of the parietal pleura and the extremely long biopersistence of the amphiboles now finally explain how very low exposures can cause mesothelioma in susceptible subjects and why the neoplasm always occurs on the parietal pleura.

CONCLUSIONS: In medical-legal assessments of cases of mesothelioma the etiological importance of the ultrathin fraction of fibres means that any assumption of the disease being avoidable must be discarded, at least up to the second half of the 1980s because until then this class of fibres, which today must be considered as the true causal agent of the neoplasm, was not visible under the optical microscope, nor could such fibres be measured or eliminated from the atmosphere of working environments. The filter materials available both for fixed ventilation systems and for individual protective masks were not able to block the ultrathin fibres and were therefore only efficacious for the prevention of asbestosis and probably pulmonary carcinoma. It was only with the use of highly efficient HEPA filters and "absolute" filters towards the end of the 1980s that efficacious protection against all size classes of respirable fibres became possible in industrial plants. Preventive measures in the public hygiene area must also take account of the aetiological role of ultrathin fibres by making full use of electron microscope investigations and by using "absolute" filters for domestic purposes, in ventilation systems and above all in the filter systems of the mechanical devices used in town street cleaning operations.}, } @article {pmid15841689, year = {2004}, author = {Henderson, DW and Rödelsperger, K and Woitowitz, HJ and Leigh, J}, title = {After Helsinki: a multidisciplinary review of the relationship between asbestos exposure and lung cancer, with emphasis on studies published during 1997-2004.}, journal = {Pathology}, volume = {36}, number = {6}, pages = {517-550}, doi = {10.1080/00313020400010955}, pmid = {15841689}, issn = {0031-3025}, mesh = {Adenocarcinoma/epidemiology/*etiology/pathology ; Asbestos/*adverse effects ; Asbestosis/*complications/pathology ; Causality ; Cocarcinogenesis ; Environmental Exposure/*adverse effects ; Humans ; Lung Neoplasms/epidemiology/*etiology/pathology ; Smoking/adverse effects ; }, abstract = {Despite an extensive literature, the relationship between asbestos exposure and lung cancer remains the subject of controversy, related to the fact that most asbestos-associated lung cancers occur in those who are also cigarette smokers: because smoking represents the strongest identifiable lung cancer risk factor among many others, and lung cancer is not uncommon across industrialised societies, analysis of the combined (synergistic) effects of smoking and asbestos on lung cancer risk is a more complex exercise than the relationship between asbestos inhalation and mesothelioma. As a follow-on from previous reviews of prevailing evidence, this review critically evaluates more recent studies on this relationship--concentrating on those published between 1997 and 2004--including lung cancer to mesothelioma ratios, the interactive effects of cigarette smoke and asbestos in combination, and the cumulative exposure model for lung cancer induction as set forth in The Helsinki Criteria and The AWARD Criteria (as opposed to the asbestosis-->cancer model), together with discussion of differential genetic susceptibility/resistance factors for lung carcinogenesis by both cigarette smoke and asbestos. The authors conclude that: (i) the prevailing evidence strongly supports the cumulative exposure model; (ii) the criteria for probabilistic attribution of lung cancer to mixed asbestos exposures as a consequence of the production and end-use of asbestos-containing products such as insulation and asbestos-cement building materials--as embodied in The Helsinki and AWARD Criteria--conform to, and are further consolidated by, the new evidence discussed in this review; (iii) different attribution criteria (e.g., greater cumulative exposures) are appropriate for chrysotile mining/milling and perhaps for other chrysotile-only exposures, such as friction products manufacture, than for amphibole-only exposures or mixed asbestos exposures; and (iv) emerging evidence on genetic susceptibility/resistance factors for lung cancer risk as a consequence of cigarette smoking, and potentially also asbestos exposure, suggests that genotypic variation may represent an additional confounding factor potentially affecting the strength of association and hence the probability of causal contribution in the individual subject, but at present there is insufficient evidence to draw any meaningful conclusions concerning variation in asbestos-mediated lung cancer risk relative to such resistance/susceptibility factors.}, } @article {pmid15835628, year = {2005}, author = {Baas, P and Sleeswijk, P and Strankinga, WF and van Hezik, EJ and Burgers, JA and Tan, KY and Schouwink, JH}, title = {[Problematic cases of mesothelioma reported to the Dutch Institute for Asbestos Victims: evaluation by the Mesothelioma Working Group of the Netherlands Association of Pulmonologists and Specialists in Tuberculosis].}, journal = {Nederlands tijdschrift voor geneeskunde}, volume = {149}, number = {14}, pages = {759-763}, pmid = {15835628}, issn = {0028-2162}, mesh = {Aged ; Aged, 80 and over ; Air Pollutants ; Asbestos/*adverse effects ; Environmental Exposure ; Female ; Humans ; Male ; Mesothelioma/diagnosis/*etiology/pathology ; Middle Aged ; Netherlands ; Occupational Diseases/diagnosis/*etiology/pathology ; Occupational Exposure ; Pleural Neoplasms/diagnosis/*etiology/pathology ; }, abstract = {OBJECTIVE: To analyse the assessments of problematic cases reported to the Dutch Institute for Asbestos Victims (IAS) by the Mesothelioma Working Party of the Netherlands Association of Pulmonologists and Specialists in Tuberculosis (NVALT).

DESIGN: Descriptive.

METHOD: The pathological confirmation of a malignant pleural mesothelioma of occupational origin is difficult in about 10% of the cases. The IAS has requested the Mesothelioma Working Party of the NVALT to review these cases. When no definitive diagnosis can be made on histological or cytological grounds, three pulmonologists reach a conclusion on the basis of correspondence, X-ray examination and other information.

RESULTS: In the period January 2000--March 2004 the Working Party evaluated 132 cases, two-thirds of whom (n = 89) were assessed to be compatible with 'malignant pleural mesothelioma' and one-third of whom (n = 43) were felt to be non-compatible. In 69% of the cases (91/132) the conclusions of the three independent specialists were unanimous. The median time from request to report was 25 days (range: 1-185).

CONCLUSION: This approach was effective and rapid.}, } @article {pmid15833832, year = {2005}, author = {Cristaudo, A and Foddis, R and Vivaldi, A and Buselli, R and Gattini, V and Guglielmi, G and Cosentino, F and Ottenga, F and Ciancia, E and Libener, R and Filiberti, R and Neri, M and Betta, P and Tognon, M and Mutti, L and Puntoni, R}, title = {SV40 enhances the risk of malignant mesothelioma among people exposed to asbestos: a molecular epidemiologic case-control study.}, journal = {Cancer research}, volume = {65}, number = {8}, pages = {3049-3052}, doi = {10.1158/0008-5472.CAN-04-2219}, pmid = {15833832}, issn = {0008-5472}, mesh = {Aged ; Asbestos/*poisoning ; Case-Control Studies ; *Cocarcinogenesis ; DNA, Neoplasm/genetics ; Female ; Humans ; Male ; Mesothelioma/epidemiology/*etiology/genetics/virology ; Molecular Epidemiology ; Polymerase Chain Reaction ; Polyomavirus Infections/*complications/virology ; Simian virus 40/genetics/*physiology ; Tumor Virus Infections/*complications/virology ; Urinary Bladder Neoplasms/epidemiology/etiology/genetics/virology ; }, abstract = {We conducted a case-control study on asbestos exposure and presence of SV40 in tumor samples of malignant mesotheliomas (MMs) and bladder urotheliomas (BUs). PCR analysis revealed the presence of SV40 DNA (SV40+) in eight (42.1%) MMs and 6 (33.3%) BUs. The odds ratio for MM Asb- and SV40+ was 0.4 [95% confidence interval (95% CI), 0.03-4.0], for Asb+ and SV40- was 3.6 (95% CI, 0.6-21.0), and for Asb+ and SV40+ was 12.6 (95% CI, 1.2-133.9). Our results suggest that SV40 increases the risk of MM among individuals exposed to asbestos.}, } @article {pmid15830375, year = {2005}, author = {Vintman, L and Nielsen, S and Berner, A and Reich, R and Davidson, B}, title = {Mitogen-activated protein kinase expression and activation does not differentiate benign from malignant mesothelial cells.}, journal = {Cancer}, volume = {103}, number = {11}, pages = {2427-2433}, doi = {10.1002/cncr.21014}, pmid = {15830375}, issn = {0008-543X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Enzyme Activation ; Female ; Humans ; JNK Mitogen-Activated Protein Kinases/*metabolism ; MAP Kinase Kinase 4 ; Male ; Mesothelioma/diagnosis/*enzymology ; Middle Aged ; Mitogen-Activated Protein Kinase 3/*metabolism ; Mitogen-Activated Protein Kinase Kinases/*metabolism ; Phosphorylation ; p38 Mitogen-Activated Protein Kinases/*metabolism ; }, abstract = {BACKGROUND: In vitro studies of malignant mesothelioma (MM) cells have suggested activation of mitogen-activated protein kinase (MAPK) in response to asbestos exposure. The objective of this study was to investigate protein expression (level) and phosphorylation status (activity) of the extracellular-regulated kinase (ERK), the c-Jun amino-terminal kinase (JNK), and the high-osmolarity glycerol response kinase (p38) in vivo through the analysis of fresh frozen reactive mesothelium (RM) and MM specimens.

METHODS: MAPK levels were analyzed in 36 fresh-frozen MM specimens (32 effusions, 4 biopsies) and in 14 RM specimens (all effusions) using immunoblotting with antibodies detecting the total (pan-) and activated (phospho-) fraction (p-) of ERK, JNK, and p38. Values for pan-MAPK and p-MAPK expression and the p-MAPK/pan-MAPK ratio in MM and RM specimens were compared. Results were corroborated using immunocytochemistry for p-ERK, p-JNK, and p-38 in selected specimens.

RESULTS: Pan-ERK, pan-JNK, and pan-p38 expression was found frequently in both MM specimens (35 of 36 specimens) and RM specimens (14 of 14 specimens) using immunoblotting, with comparable findings for activated p-p38 (34 of 36 MM specimens, 13 of 14 RM specimens). Activation of p-ERK (27 of 36 MM specimens, 10 of 14 RM specimens) and p-JNK (25 of 36 MM specimens, 10 of 14 RM specimens) was less frequent. Pan-ERK (P = 0.016), pan-JNK (P = 0.004), pan-p38 (P = 0.012), and p-ERK (P = 0.02) expression levels were higher in MM specimens from female patients. Pan-p38 expression levels also were higher in peritoneal MM specimens (P = 0.019). MM and RM showed similar MAPK expression, activation, and activation ratios (Mann-Whitney test; P > 0.05). Immunocytochemistry localized MAPK to MM and RM cells.

CONCLUSIONS: The current results provided the first evidence of in vivo activation of MAPK in clinical MM and RM. The similar values in these two cell types suggest that MAPK may not be involved in the transformation of benign to malignant mesothelium, thus bringing into question the validity of using MAPKs as molecular therapeutic targets in patients with MM.}, } @article {pmid15828074, year = {2005}, author = {Nam, JM and Rice, C and Gail, MH}, title = {Comparison of asbestos exposure assessments by next-of-kin respondents, by an occupational hygienist, and by a job-exposure matrix from the National Occupational Hazard Survey.}, journal = {American journal of industrial medicine}, volume = {47}, number = {5}, pages = {443-450}, doi = {10.1002/ajim.20168}, pmid = {15828074}, issn = {0271-3586}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Bias ; Case-Control Studies ; Death Certificates ; *Family ; Health Surveys ; Humans ; Los Angeles/epidemiology ; Mental Recall ; Mesothelioma/epidemiology/*etiology/mortality ; Middle Aged ; New York/epidemiology ; Occupational Exposure/adverse effects/analysis/*statistics & numerical data ; Occupational Medicine ; Proxy ; Registries ; Reproducibility of Results ; Risk Assessment/methods ; }, abstract = {BACKGROUND: Assessments of occupational exposures in case-control studies of rapidly fatal illnesses often rely on data from next-of-kin respondents, which may be inaccurate.

METHODS: Three methods for assessing exposure to asbestos from case-control data on mesothelioma, including next-of-kin assessment, expert assessment, and use of a generic job-exposure matrix (JEM). Interview data [Spirtas et al. (1994): Occup Environ Med 51:804-811] were reviewed to determine exposure status by an occupational hygienist (C.R.) who was unaware of disease status. Exposure odds ratios were calculated using standard methods, and measures of agreement included the kappa statistic and conditional and marginal odds ratios.

RESULTS: Expert assessment detected higher proportions of exposed subjects than the next-of-kin respondents or JEM methods. The disease-exposure odds ratios were highest for respondents, perhaps because of recall bias, and lowest for the JEM method. The agreement was highest between the respondent and expert assessments. A combination of respondent's assessment and JEM assessment led to the best prediction of the expert's assessment. Results for spouse respondents were similar to those for other "next-of-kin" respondents.

CONCLUSIONS: Expert assessments were the most plausible, but the data indicate that disease associations could also be detected with the other exposure assessment methods. Using some combination of the proxy respondent's assessment and the JEM assessment, one can predict the expert's assessment. A strategy that relied on the respondent's assessment when it was positive and otherwise obtained an expert assessment could reduce costs with little error, compared to expert assessment on all subjects.}, } @article {pmid15828068, year = {2005}, author = {Miller, A}, title = {Mesothelioma in household members of asbestos-exposed workers: 32 United States cases since 1990.}, journal = {American journal of industrial medicine}, volume = {47}, number = {5}, pages = {458-462}, doi = {10.1002/ajim.20167}, pmid = {15828068}, issn = {0271-3586}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Air Pollution, Indoor/*adverse effects ; Asbestos/*toxicity ; Child ; Clothing ; Family Characteristics ; *Family Health ; Female ; Humans ; Inhalation Exposure/adverse effects ; Laundering ; Lung Neoplasms/epidemiology/*etiology ; Male ; Medical Records ; Mesothelioma/epidemiology/*etiology ; Middle Aged ; Nuclear Family ; Occupational Exposure/*adverse effects/statistics & numerical data ; Time Factors ; United States/epidemiology ; }, abstract = {BACKGROUND: Mesothelioma is significant as an indicator of asbestos exposure, as a continuing major cause of death in those exposed, and as a risk following lesser exposures. One such exposure is living in the household of an asbestos worker, and coming into contact with fibers brought home on his/her body, clothing, etc.

METHODS: Law firms throughout the US known for their pursuit of asbestos claims were polled for mesothelioma claims brought on behalf of family members of identifiable asbestos-exposed workers. Cases with any occupational, environmental, or other possible exposure were not included.

RESULTS: This study reports 32 household-exposure mesothelioma cases, diagnosed since 1990. Relationships were wife (15), daughter (11), son (3), sister-in law (1), niece (1), and boarder (1). Occupations of the workers included shipyard (13), insulator (7), and other (12). Of the 27 pleural cases, 13 were epithelial, 5 fibrous, 3 biphasic, and 6 not specified; of the 5 peritoneal cases, 4 were epithelial and 1 fibrous. Latency was greater than 40 years in 27 cases; 6 cases were 40-49 years of age and 17 were 60 or older.

CONCLUSIONS: Records from law firms were a useful source of information. Mesothelioma resulting from household exposure is a continuing problem. It is more likely to present in the elderly, after latencies of >40 years.}, } @article {pmid15820729, year = {2005}, author = {Browne, ML and Varadarajulu, D and Lewis-Michl, EL and Fitzgerald, EF}, title = {Cancer incidence and asbestos in drinking water, Town of Woodstock, New York, 1980-1998.}, journal = {Environmental research}, volume = {98}, number = {2}, pages = {224-232}, doi = {10.1016/j.envres.2004.07.017}, pmid = {15820729}, issn = {0013-9351}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects/analysis ; Drinking ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Neoplasms/*epidemiology/etiology ; New York/epidemiology ; Prospective Studies ; Risk Factors ; Sex Factors ; Water Pollutants, Chemical/*adverse effects/analysis ; Water Supply/*standards ; }, abstract = {Late in 1985, asbestos contamination was discovered in the public water supply of the Town of Woodstock, Ulster County, New York. Contamination resulted from asbestos-cement pipes installed in the town water system in the mid to late 1950s and the corrosiveness of the local water. The New York State (NYS) Department of Health established the Woodstock Asbestos Exposure Registry (WAER) in 1986 to monitor rates of cancer among individuals who lived on the water supply between 1960 and 1985. Demographic, health, and residential information were collected on 2936 registrants. The follow-up period for observation of cancer was 1980-1998, consistent with the expected lag of 20-30+ years for development of asbestos-related cancers. The NYS Cancer Registry was used to ascertain cancer diagnoses. Standardized incidence ratios (SIRs) for gastrointestinal, respiratory, and total cancers were all approximately 1.00 or less and all 95% confidence intervals (CIs) included 1.00. For individual types of the gastrointestinal cancers, only the SIR for pancreatic cancer was marginally statistically significant at 2.19 (95% CI=1.00-4.16), based on a total of nine observed cases. The excess in pancreatic cancer occurred primarily among men (SIR=3.08; 95% CI=1.13-6.70) and was only slightly elevated among women (SIR=1.39; 95% CI=0.29-4.06). This association may be related to factors other than asbestos exposure such as occupation and lifestyle or to chance. No cases of mesothelioma were observed among WAER participants. There was no increase in incidence by latency or duration of residence on the water supply, but the ability to detect these trends is limited by small numbers and unknown dates of initial exposure. The general pattern of results did not demonstrate a likely link between exposure to asbestos in drinking water and cancer occurrence among participants in the WAER.}, } @article {pmid15816607, year = {2005}, author = {Tanvetyanon, T and Elmishad, AG and Carbone, M}, title = {Development of malignant mesothelioma during treatment for prolymphocytic leukemia: is asbestos or simian virus 40 a link?.}, journal = {Anticancer research}, volume = {25}, number = {1B}, pages = {429-433}, pmid = {15816607}, issn = {0250-7005}, support = {R01CA92657/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Asbestos/*adverse effects ; Blotting, Southern ; Bone Marrow/metabolism ; DNA Primers/chemistry ; DNA, Viral/metabolism ; Disease Progression ; Humans ; Immunosuppressive Agents/pharmacology ; Leukemia, Prolymphocytic/*pathology ; Lung Neoplasms/*etiology/*secondary ; Male ; Mesothelioma/*etiology/*secondary ; Polymerase Chain Reaction ; Simian virus 40/*metabolism ; Tomography, X-Ray Computed ; Vidarabine/*analogs & derivatives/pharmacology ; }, abstract = {A patient with a history of heavy asbestos exposure presented with B-prolymphocytic leukemia/lymphoma (B-PLL). Soon after, he developed rapidly progressing malignant peritoneal mesothelioma. The concurrent development of both relatively uncommon diseases raised the possibility that a common causative factor might exist. Since asbestos, simian virus 40 (SV40), or both have been associated with lymphoproliferative disease and mesothelioma, we investigated both possible links in our patient. Imaging studies provided evidence for asbestos exposure because bilateral pleural plaques were identified. Tissues from bone marrow (involved with B-PLL) and from a peritoneal nodule (involved with mesothelioma) were examined for SV40 DNA using polymerase chain reaction (PCR): no SV40 DNA was detected. We conclude that asbestos remains the sole possible connection to both malignancies in this patient. It seems possible that fludarabine, an immunosuppressive chemotherapy, accelerated the occurrence and progression of malignant mesothelioma during the therapy for his B-PLL.}, } @article {pmid15790520, year = {2005}, author = {Wu, P and Hyodoh, F and Hatayama, T and Sakaguchi, H and Hatada, S and Miura, Y and Takata-Tomokuni, A and Katsuyama, H and Otsuki, T}, title = {Induction of CD69 antigen expression in peripheral blood mononuclear cells on exposure to silica, but not by asbestos/chrysotile-A.}, journal = {Immunology letters}, volume = {98}, number = {1}, pages = {145-152}, doi = {10.1016/j.imlet.2004.11.005}, pmid = {15790520}, issn = {0165-2478}, mesh = {Antibodies ; Antigens, CD/biosynthesis/genetics/*immunology ; Antigens, Differentiation, T-Lymphocyte/biosynthesis/genetics/*immunology ; Asbestos, Serpentine/*pharmacology ; Coculture Techniques ; Humans ; Lectins, C-Type ; Leukocytes, Mononuclear/*drug effects ; Protein Kinase C/antagonists & inhibitors ; }, abstract = {While cases of silicosis are often complicated by various autoimmune disorders, patients with asbestosis develop malignant tumors such as lung cancer and malignant mesothelioma. These differences may derive from different biological effects, particularly on immunological cells, of silica and asbestos. To find differences between silica and asbestos, the early activation antigen, CD69, on T cells was examined because dysregulated and continuous activation of T cells may promote the survival of self-recognizing T cells. After cultivation of peripheral blood mononuclear cells with or without silica or chrysotile-A, an asbestos, only silica induced CD69 expression on the lymphocytes. This induction of CD69 expression was mediated by protein kinase C activation. In addition, cell-cell contact mediated by HLA-DR was more important than soluble factors secreted from silica-phagocytosed cells such as IL-1beta, IL-6, and IL-8, even though IL-6 and IL-8 were produced during the culture of PBMCs with silica and chrysotile-A. It should be examined how these activated, CD69-expressing lymphocytes affect other immune systems as well as alter themselves in terms of cytokine production and cell-cell interaction, leading to autoimmune disorders in silicosis patients.}, } @article {pmid15778255, year = {2005}, author = {Sorahan, T and Kinlen, LJ and Doll, R}, title = {Cancer risks in a historical UK cohort of benzene exposed workers.}, journal = {Occupational and environmental medicine}, volume = {62}, number = {4}, pages = {231-236}, pmid = {15778255}, issn = {1470-7926}, mesh = {Benzene/*toxicity ; Carcinogens, Environmental/*toxicity ; Cause of Death ; Cohort Studies ; England/epidemiology ; Female ; Humans ; Incidence ; Leukemia/mortality ; Leukemia, Myeloid, Acute/mortality ; Lip Neoplasms/mortality ; Lung Neoplasms/mortality ; Male ; Neoplasms/chemically induced/*mortality ; Occupational Diseases/chemically induced/*mortality ; Occupational Exposure/adverse effects ; Risk Factors ; Wales/epidemiology ; }, abstract = {AIMS: To examine mortality from different causes and cancer incidence among a cohort of benzene workers in England and Wales.

METHODS: A cohort of 5514 workers who had been occupationally exposed to benzene in 1966/67 or earlier was assembled by the former Factory Inspectorate and the Medical Research Council from details provided by 233 employers in England and Wales. The cohort was followed up for mortality (1968-2002) and cancer registrations (1971-2001). National mortality rates and cancer registration (incidence) rates were used to calculate standardised mortality ratios and standardised registration ratios.

RESULTS: Mortality was close to expectation for all causes and significantly increased for cancer of the lip, cancer of the lung and bronchus, secondary and unspecified cancers, acute non-lymphocytic leukaemia (ANLL), and all neoplasms. Significant deficits were shown for three non-malignant categories (mental disorders, diseases of the digestive system, accidents). SMRs for other leukaemia, lymphomas, and multiple myeloma were close to or below expectation. There was some evidence of under-ascertainment of cancer registrations, although significantly increased SRRs were shown for lung cancer and cancer of the pleura (mesothelioma).

CONCLUSIONS: Many study subjects would have been exposed to carcinogens other than benzene (for example, asbestos, rubber industry fumes, foundry fumes, polycyclic aromatic hydrocarbons), and the excesses of lung cancer and mesothelioma are likely to reflect exposures to these other carcinogens. The carcinogenic effects of benzene exposure on the lymphohaematopoietic system were limited to ANLL.}, } @article {pmid15777968, year = {2005}, author = {Wali, A and Morin, PJ and Hough, CD and Lonardo, F and Seya, T and Carbone, M and Pass, HI}, title = {Identification of intelectin overexpression in malignant pleural mesothelioma by serial analysis of gene expression (SAGE).}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {48}, number = {1}, pages = {19-29}, doi = {10.1016/j.lungcan.2004.10.011}, pmid = {15777968}, issn = {0169-5002}, mesh = {Asbestos, Crocidolite/adverse effects ; Blotting, Western ; Case-Control Studies ; Colonic Neoplasms/genetics ; Cytokines ; Databases, Genetic ; Female ; GPI-Linked Proteins ; *Gene Expression Profiling ; Humans ; Immunohistochemistry ; Lectins/*biosynthesis/genetics ; Mesothelioma/*genetics/surgery ; Ovarian Neoplasms/genetics ; Pleural Neoplasms/*genetics/surgery ; Polyomavirus Infections/complications ; RNA, Messenger/biosynthesis ; Reverse Transcriptase Polymerase Chain Reaction ; Tumor Cells, Cultured ; Tumor Virus Infections/complications ; }, abstract = {Malignant pleural mesothelioma (MPM) is a fatal neoplasm with no acceptable curative approaches. We used serial analysis of gene expression (SAGE) to compare the gene expression pattern of a surgically resected MPM to the autologous normal mesothelium. Intelectin gene overexpression (>139-fold) was found in the tumor. Online SAGE datasets revealed intelectin to be consistently present in mesothelioma(s), ovarian cancer, and colon cancer. Intelectin mRNA expression was found by RT-PCR in 4 of 5 resected MPM tumors, and Intelectin protein expression was confirmed by immunohistochemistry in 28 of 53 MPM tumors, and in 4 of 4 mesothelioma cell lines studied by Western blot. A marked induction in intelectin gene expression was observed among human primary mesothelial cells as a consequence of crocidolite asbestos exposure and simian virus 40 infection. Intelectin overexpression in mesothelioma could have potential screening, and therapeutic implications.}, } @article {pmid15772581, year = {2005}, author = {Amsalhem, P and Kuhnle, M and Bellamy, J and Coblence, JF and Leroy-Terquem, E}, title = {[Lung cancer and peritoneal mesothelioma: two complications of asbestos exposure in the same patient].}, journal = {Revue de pneumologie clinique}, volume = {61}, number = {1 Pt 1}, pages = {47-49}, doi = {10.1016/s0761-8417(05)84783-2}, pmid = {15772581}, issn = {0761-8417}, mesh = {Aged ; Asbestos/*adverse effects ; *Environmental Exposure ; Fatal Outcome ; Humans ; Lung Neoplasms/*etiology/pathology ; Male ; Mesothelioma/*etiology/pathology ; Peritoneal Neoplasms/*etiology/pathology ; }, abstract = {INTRODUCTION: Association of a lung cancer and a malignant peritoneal mesothelioma is reported in a 78-year-old patient with significant asbestos exposure.

OBSERVATION: After exploration of an intra-pulmonary opacity, with inspissated pleura, the diagnosis of primary pulmonary adenocarcinoma was obtained by thoracotomy in April 1999. In February 2002, the diagnosis of peritoneal mesothelioma was made by laparoscopy. The course was marked by irreducible ascites and was fatal 7 months after the diagnosis of peritoneal mesothelioma.

CONCLUSION: Malignant mesothelioma is a rare disease and even rare in association with lung cancer.}, } @article {pmid15766468, year = {2005}, author = {Isidro Montes, I and Abu Shams, K and Alday, E and Carretero Sastre, JL and Ferrer Sancho, J and Freixa Blanxart, A and Monsó Molas, E and Pascal Martínez, I and Rodríguez Becerra, E and Rodríguez Panadero, F and , }, title = {[Guidelines on asbestos-related pleuropulmonary disease].}, journal = {Archivos de bronconeumologia}, volume = {41}, number = {3}, pages = {153-168}, doi = {10.1016/s1579-2129(06)60416-3}, pmid = {15766468}, issn = {0300-2896}, mesh = {Asbestos/*adverse effects ; *Asbestosis/diagnosis/diagnostic imaging/epidemiology ; Bronchoalveolar Lavage Fluid ; Bronchoscopy ; Data Interpretation, Statistical ; Diagnosis, Differential ; Environmental Exposure/*adverse effects ; Female ; Humans ; Incidence ; Lung Diseases/*etiology ; Lung Neoplasms/diagnosis/*etiology/surgery ; Male ; Mesothelioma/diagnosis/*etiology/surgery ; Occupational Exposure/*adverse effects ; Odds Ratio ; Pleural Diseases/*etiology ; Pleural Neoplasms/diagnosis/*etiology/surgery ; Prevalence ; Pulmonary Atelectasis/etiology ; Pulmonary Fibrosis/diagnosis ; Radiography, Thoracic ; Risk Factors ; Sex Factors ; Spain ; }, } @article {pmid15757980, year = {2005}, author = {McElvenny, DM and Darnton, AJ and Price, MJ and Hodgson, JT}, title = {Mesothelioma mortality in Great Britain from 1968 to 2001.}, journal = {Occupational medicine (Oxford, England)}, volume = {55}, number = {2}, pages = {79-87}, doi = {10.1093/occmed/kqi034}, pmid = {15757980}, issn = {0962-7480}, mesh = {Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Mesothelioma/etiology/*mortality ; Middle Aged ; Mortality/trends ; Occupational Diseases/*mortality ; Registries ; United Kingdom/epidemiology ; }, abstract = {BACKGROUND: The British mesothelioma register contains all deaths from 1968 to 2001 where mesothelioma was mentioned on the death certificate.

AIMS: To present summary statistics of the British mesothelioma epidemic including summaries by occupation and geographical area.

METHODS: Standardized mortality ratios (SMRs) were calculated for local authorities, unitary authorities and counties. Temporal trends in SMRs were also examined. Proportional mortality ratios (PMRs) were calculated using the Southampton (based on the 1980 standard occupational classification) coding scheme. Temporal trends in PMRs were also examined.

RESULTS: The annual number of mesothelioma deaths has increased from 153 in 1968 to 1848 in 2001. Current deaths in males account for about 85% of the cases. The areas of West Dunbartonshire (SMR 637), Barrow-in-Furness (593), Plymouth (396) and Portsmouth (388) have the highest SMRs over the period 1981-2000. The occupations with the highest PMRs are metal plate workers (PMR 503), vehicle body builders (526), plumbers and gas fitters (413) and carpenters (388).

CONCLUSIONS: These data reinforce earlier findings that geographical areas and occupations associated with high exposure to asbestos in the past continue to drive the mesothelioma epidemic in Great Britain. However, the trends over time suggest a change in the balance of risk away from traditional asbestos exposure industries to industries where one could describe the exposure as secondary, such as plumbers and gas fitters, carpenters, and electricians.}, } @article {pmid15755062, year = {2004}, author = {Pylev, LN and Vasil'eva, LA and Stadnikova, NM and Smirnova, OV}, title = {[The role of macrophages in asbestos-induced carcinogenesis].}, journal = {Voprosy onkologii}, volume = {50}, number = {6}, pages = {678-682}, pmid = {15755062}, issn = {0507-3758}, mesh = {Animals ; Asbestos/*adverse effects ; Carcinogens/*adverse effects ; Cell Transformation, Neoplastic ; Cells, Cultured ; Epithelium/drug effects/metabolism/*pathology ; Female ; Macrophages, Peritoneal/*metabolism ; Mesothelioma/*chemically induced/*metabolism ; Rats ; Reactive Oxygen Species/metabolism ; Tumor Cells, Cultured ; }, abstract = {Data available on the pathways of asbestos (fibrous) carcinogenesis still leaves much to be desired. Asbestos is regarded as a non-genotoxic substance by most researchers. There is insufficient evidence on the interaction of fibres, target-cells and macrophages. Macrophages secreted proteins (ca. 450 kD) to inhibit proliferation of intact mesothelium and cytoxine (3-5 kD) which stimulated the cellular sensitivity of intact mesothelium and mesotheliomas to the toxic influence of asbestos. It was suggested that the effect was due to the triggering of intrinsic causation of cell death. Like any other fibres, carcinogenic effect of asbestos could be accounted for by such significant factor as active oxygen radicals. When exposed to asbestos, both intact mesothelial and mesothelioma cells and macrophages synthesized those substances. Free radical-like substances in conjunction with macrophage-conditioned media produced toxic effect on mesothelial cells. The role of active oxygen radicals in fibre-induced carcinogenesis is discussed.}, } @article {pmid15754636, year = {2004}, author = {Fijałkowski, M and Jochymski, C}, title = {[Pleural mesothelioma--case with effusion in both pleural cavities].}, journal = {Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego}, volume = {17}, number = {101}, pages = {479-482}, pmid = {15754636}, issn = {1426-9686}, mesh = {Diagnosis, Differential ; Humans ; Male ; Mesothelioma/*complications/*diagnosis/pathology ; Middle Aged ; Pleural Effusion, Malignant/diagnosis/drug therapy/*etiology ; Pleural Neoplasms/*complications/*diagnosis/pathology ; }, abstract = {Etiology of the pleural exudate is not always easy to establish with the routine diagnostic procedures. We report the history of a 55-year-old man, driver--without evident occupational exposure to asbestos dust. Patient was treated in hospital because of recurrent bilateral sanguineous pleural fluid. Repeated basic laboratory examinations of pleural exudate did not contribute to establishing etiology of the disease. At the beginning of hospital stay antituberculosis therapy was applied but was unsuccessful. Rapid accumulation of the fluid, deterioration of general condition of the patient, presence of dysplasia in the cells of the sediment of the exudate indicated possibility of diagnosis of neoplasm of the pleura. Intravenous injections of cisplatin and intrapleural application of bleomycin did not influence, however, the course of the disease. Final diagnosis was possible only after pleural biopsy (with Abrams needle) was performed. Histopathologic examination of the specimen disclosed: malignant mesothelioma biphasic type. Patient died after 3 months of observations and attempt at treatment.}, } @article {pmid15745251, year = {2004}, author = {Li, L and Sun, TD and Zhang, X and Lai, RN and Li, XY and Fan, XJ and Morinaga, K}, title = {Cohort studies on cancer mortality among workers exposed only to chrysotile asbestos: a meta-analysis.}, journal = {Biomedical and environmental sciences : BES}, volume = {17}, number = {4}, pages = {459-468}, pmid = {15745251}, issn = {0895-3988}, mesh = {Asbestos, Serpentine/*adverse effects ; Cohort Studies ; Dose-Response Relationship, Drug ; Humans ; Lung Neoplasms/etiology/mortality ; Mesothelioma/etiology/mortality ; Neoplasms/chemically induced/*mortality ; *Occupational Exposure ; *Occupational Health ; Risk Assessment ; Stomach Neoplasms/etiology/mortality ; }, abstract = {OBJECTIVE: To determine whether there was excessive risk of cancer among workers exposed to chrysotile fiber alone by applying a meta-analysis technique.

METHODS: All data meeting the criteria of cohort studies on cancer mortality among workers exposed only to chrysotile were incorporated into meta-analysis. Pooled standardized mortality ratios (SMRs) and their corresponding 95% confidence intervals (CIs) for main cancer sites were calculated using two approaches of unweighted ratio and random effect model. The heterogeneity and its sources of the results were examined with a Q-statistic and Z-score test. The dose-response effect as reflected in the percentage of all deaths due to mesothelioma served as a proxy measure of chrysotile exposure.

RESULTS: A cohort of twenty six workers exposed to chrysotile alone was summarized. The significantly elevated meta-SMRs for all deaths (1.27), all cancers (1.28), cancers of respiratory organs (2.51), cancers of lung (2.35) and cancers of stomach (1.24) were observed. The significantly elevated meta-SMRs for lung cancer within occupational strata were observed among textile workers (3.55), asbestos product manufacturers (3.30), miners and millers (2.24), cement product workers (1.22), and for stomach cancer among asbestos product manufacturers (1.49). Meta-SMRs for cancers at other sites were not significant. Meta-SMR for lung cancer showed an increasing trend with an elevated percentage of all deaths from mesothelioma, but no such trend for stomach cancer.

CONCLUSION: There are excessive risks of lung cancer and mesothelioma among workers exposed to chrysotile fiber alone, and likely no convincing indication of an etiological association between chrysotile exposure and cancers at other sites.}, } @article {pmid15729420, year = {2005}, author = {Lagrotteria, DD and Tsang, B and Elavathil, LJ and Tomlinson, CW}, title = {A case of primary malignant pericardial mesothelioma.}, journal = {The Canadian journal of cardiology}, volume = {21}, number = {2}, pages = {185-187}, pmid = {15729420}, issn = {0828-282X}, mesh = {Adult ; Cardiac Tamponade/etiology ; Fatal Outcome ; Heart Neoplasms/complications/*pathology ; Humans ; Male ; Mesothelioma/complications/*pathology ; Pericardial Effusion/etiology ; Pericardium/*pathology ; }, abstract = {Primary malignant pericardial mesothelioma (PMPM) is an exceedingly rare tumour. One of the largest necropsy series gave an incidence of primary pericardial tumours of 0.0022%, of which mesothelioma is the most common type. In a Canadian epidemiological survey, the annual incidence of PMPM was reported to be one in 40 million. A male predominance of the disease has been described, and the majority of cases occur in the fourth to seventh decades of life. There has been no definite association between asbestos exposure and pericardial disease. Due to its generally late presentation and poor response to therapy, the prognosis is very poor. The present report discusses the case of a 43-year-old man who presented with cardiac tamponade and was subsequently diagnosed with PMPM. Cardiac tamponade is a known complication of the malignancy, but it is rarely the first manifestation of cancer. The patient's clinical course was a result of the aggressive nature of PMPM. Effusive constrictive pericarditis and restrictive cardiomyopathy were likely contributors to this patient's disease burden. These processes should be considered and managed appropriately in patients who do not respond to pericardiocentesis or pericardial window as treatment for pericardial tamponade.}, } @article {pmid15723885, year = {2005}, author = {López-Abente, G and Hernández-Barrera, V and Pollán, M and Aragonés, N and Pérez-Gómez, B}, title = {Municipal pleural cancer mortality in Spain.}, journal = {Occupational and environmental medicine}, volume = {62}, number = {3}, pages = {195-199}, pmid = {15723885}, issn = {1470-7926}, mesh = {Asbestos/adverse effects ; Bayes Theorem ; Female ; Humans ; Male ; Pleural Neoplasms/etiology/*mortality ; Risk Assessment/methods ; Space-Time Clustering ; Spain/epidemiology ; Urban Health ; }, abstract = {BACKGROUND: Pleural cancer is a recognised indicator of exposure to asbestos and mesothelioma mortality.

AIMS: To investigate the distribution of municipal mortality due to this tumour, using the autoregressive spatial model proposed by Besag, York, and Mollie.

METHODS: It was possible to compile and ascertain the posterior distribution of relative risk on the basis of a single Bayesian spatial model covering all of Spain's 8077 municipal areas. Maps were plotted depicting standardised mortality ratios, smoothed relative risk (RR) estimates, and the distribution of the posterior probability that RR >1.

RESULTS: There was a higher risk of death due to pleural cancer in well defined towns and areas, many of which correspond to municipalities where asbestos using industries once existed for many years, the prime example being the municipal pattern registered for Barcelona Province. The quality of mortality data, the suitability of the model used, and the usefulness of municipal atlases for environmental surveillance are discussed.}, } @article {pmid15712262, year = {2005}, author = {Roggli, VL and Langer, AM}, title = {RE: Asbestos in brakes: exposure and risk of disease.}, journal = {American journal of industrial medicine}, volume = {47}, number = {3}, pages = {276-7; author reply 278-80}, doi = {10.1002/ajim.20129}, pmid = {15712262}, issn = {0271-3586}, mesh = {Asbestos/*toxicity ; Asbestos, Serpentine/adverse effects/toxicity ; Automobiles ; Humans ; Mesothelioma/*chemically induced ; Occupational Diseases/*chemically induced ; Occupational Exposure/*adverse effects ; }, } @article {pmid15702795, year = {2005}, author = {Luo, SQ and Mu, SH and Wang, JT and Zhang, Y and Wen, QB and Cai, SP}, title = {[A study on risk of malignant neoplasm and environmental exposure to crocidolite].}, journal = {Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition}, volume = {36}, number = {1}, pages = {105-107}, pmid = {15702795}, issn = {1672-173X}, mesh = {Adult ; Aged ; Asbestos, Crocidolite/*adverse effects ; China/epidemiology ; Cohort Studies ; Environmental Exposure/*adverse effects ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/*epidemiology/etiology/mortality ; Male ; Mesothelioma/*epidemiology/etiology/mortality ; Middle Aged ; Pleural Neoplasms/epidemiology/etiology/mortality ; Retrospective Studies ; Risk Factors ; }, abstract = {OBJECTIVE: To explore the risk of developing malignant neoplasm in a cohort with the history of environmental exposure to crocidolite asbestos.

METHODS: A retrospective cohort and follow-up study covering 15 years (1987 --> 1995 --> 2001) was carrid out in a small town in Yunnan province. The cohort comprised 6254 local inhabitants. The deaths from and the RR of asbestos-related malignant neoplasms were studied.

RESULTS: There were 186 deaths from neoplasms in the observation group, the mortality being 2160.5 per 10(6) person-years (RR=1.293, 95%CI: 1.032-1.618), 20 of those deaths were caused by mesothelioma, with a crude mortality of 232.3 per 10(6) person-years (RR=17.929; 95%CI: 2.406-133.592). The mortalities for men and women were 267.5 and 186.7 per 10(6) person-years respectively. The crude mortality from lung cancer (56 deaths) was 650.5 per 10(6) person-years,there is no significance between the two groups (RR=1.434; 95%CI: 0.968-2.486). The difference in mortality from gastrointestinal cancer between the two groups is not significant, whereas the risk of man intestinal cancer in the observation is significant (RR=3.71; 95%CI: 1.077-13.270).

CONCLUSION: The risk of developing mesothelioma is significantly increased in the population with environmental exposure to crocidolite. The risk of man intestinal cancer in the town awaits additional studies.}, } @article {pmid15702125, year = {2005}, author = {Pira, E and Pelucchi, C and Buffoni, L and Palmas, A and Turbiglio, M and Negri, E and Piolatto, PG and La Vecchia, C}, title = {Cancer mortality in a cohort of asbestos textile workers.}, journal = {British journal of cancer}, volume = {92}, number = {3}, pages = {580-586}, pmid = {15702125}, issn = {0007-0920}, mesh = {Adult ; Asbestos/*adverse effects ; Cohort Studies ; Female ; Humans ; Italy/epidemiology ; Lung Neoplasms/etiology/mortality ; Male ; Mesothelioma/etiology/mortality ; Neoplasms/etiology/*mortality ; Occupational Diseases/etiology/*mortality ; Occupational Exposure ; Peritoneal Neoplasms/etiology/mortality ; Pleural Neoplasms/etiology/mortality ; Respiratory Tract Neoplasms/etiology/*mortality ; Time Factors ; }, abstract = {A cohort of 889 men and 1077 women employed for at least 1 month between 1946 and 1984 by a former Italian leading asbestos (mainly textile) company, characterised by extremely heavy exposures often for short durations, was followed up to 1996, for a total of 53,024 person-years of observation. Employment data were obtained from factory personnel records, while vital status and causes of death were ascertained through municipality registers and local health units. We observed 222 cancer deaths compared with 116.4 expected (standardized mortality ratio, SMR=191). The highest ratios were found for pleural (SMR=4105), peritoneal (SMR=1817) and lung (SMR=282) cancers. We observed direct relationships with duration of employment for lung and peritoneal cancer, and with time since first employment for lung cancer and mesothelioma. Pleural cancer risk was independent from duration (SMR=3428 for employment <1 year, 7659 for 1-4 years, 2979 for 5-9 years and 2130 for > or =10 years). Corresponding SMRs for lung cancer were 139, 251, 233 and 531. Nonsignificantly increased ratios were found for ovarian (SMR=261), laryngeal (SMR=238) and oro-pharyngeal (SMR=226) cancers. This study confirms and further quantifies the central role of latency in pleural mesothelioma and of cumulative exposure in lung cancer.}, } @article {pmid15693633, year = {2004}, author = {Yao, DX and Shia, J and Erlandson, RA and Klimstra, DS}, title = {Lymphohistiocytoid mesothelioma: a clinical, immunohistochemical and ultrastructural study of four cases and literature review.}, journal = {Ultrastructural pathology}, volume = {28}, number = {4}, pages = {213-228}, doi = {10.1080/019131290505176}, pmid = {15693633}, issn = {0191-3123}, mesh = {Adult ; Aged ; Biomarkers, Tumor/analysis ; Female ; Humans ; Immunohistochemistry ; Lung Neoplasms/metabolism/pathology/ultrastructure ; Male ; Mediastinal Neoplasms/metabolism/pathology/ultrastructure ; Mesothelioma/*metabolism/*pathology/*ultrastructure ; Microscopy, Electron, Transmission ; Middle Aged ; Pleural Neoplasms/metabolism/pathology/ultrastructure ; }, abstract = {Lymphohistiocytoid mesothelioma (LHM) is a term proposed to designate a variant of mesothelioma that assumes a histiocytoid morphology and contains intense lymphocytic infiltrates. Reports on this variant are few, and its clinicopathologic and ultrastructural characteristics are still to be defined. The authors have studied 4 such cases that were identified among 120 mesotheliomas in the electron microscopy (EM) files of a single institution between 1982 and 2002. Histologically, all 4 lesions were composed of diffuse proliferations of cells with a histiocytoid appearance, admixed with an intense lymphocytic infiltrate. All 4 were associated with an unequivocal sarcomatoid component. Immunohistochemical (IHC) studies showed that the majority of histiocytoid cells were positive for CD68 and vimentin in all 4 cases, suggesting fibrohistiocytic differentiation. Immunoreactivity for calretinin and AE1:AE3 was only very focally identified in 3 of 4 cases. All cases were negative for CEA (M), Leu-M1, and B72.3. The lymphocytic component in all 4 cases was almost entirely composed of CD3- and CD8-positive, small, mature T cells, with only a minor component of CD20-positive cells and occasional eosinophils. Although all cases contained numerous CD68 positive atypical cells, co-expression of CD68 and either calretinin or keratin by individual cells was difficult to demonstrate by immunohistochemistry. Ultrastructurally, 3 of the 4 cases demonstrated very focal mesothelial differentiation as evidenced by long and slender surface microvilli, including the case with negative immunoreactivity for calretinin and cytokeratin. Review of the literature yielded 6 additional LHM cases. Analysis of all 10 cases showed a male predominance (8:2) with a mean age of 58 years (31-73 years). All 10 cases involved the pleura. Three of 10 patients had known asbestos exposure. Six of 10 patients died of disease at 2-20 months after the diagnosis (mean, 6.9 months). The findings suggest that LHM is a distinct morphological variant of sarcomatoid mesothelioma for which mesothelial differentiation is difficult to document. Many of the cells composing these tumors exhibit fibrohistiocytic differentiation. The unusual morphological pattern of LHM makes a combined modality approach, including IHC, EM, and a knowledge of the clinical/radiologic findings, essential in achieving a correct diagnosis.}, } @article {pmid15691231, year = {2005}, author = {Jaurand, MC and Fleury-Feith, J}, title = {Pathogenesis of malignant pleural mesothelioma.}, journal = {Respirology (Carlton, Vic.)}, volume = {10}, number = {1}, pages = {2-8}, doi = {10.1111/j.1440-1843.2005.00694.x}, pmid = {15691231}, issn = {1323-7799}, mesh = {Animals ; Asbestosis/complications ; Cell Transformation, Neoplastic/pathology ; Cocarcinogenesis ; Genes, Neurofibromatosis 2 ; Genes, Tumor Suppressor ; Humans ; Mesothelioma/*etiology/genetics ; Mice ; Pleural Neoplasms/*etiology/genetics ; Polyomavirus Infections/complications ; Simian virus 40 ; Tumor Virus Infections/complications ; }, abstract = {Malignant pleural mesothelioma (MPM) results from neoplastic transformation of mesothelial cells. Past asbestos exposure represents the major risk factor for MPM, as the link between asbestos fibres and MPM has been largely proved by epidemiological and experimental studies. Asbestos fibres induce DNA and chromosome damage linked to oxidative stress following phagocytosis. Recently, simian virus 40 (SV40) has been implicated in the aetiology of MPM. The origin of human infection has been associated with SV40-contaminated polio vaccines, although to date, no epidemiological data supports this hypothesis. SV40 may act as a coactivator of asbestos in mesothelial oncogenesis. The transforming potency of SV40 results from the activity of two viral proteins, large T and small t antigens. SV40 infection stimulates production of growth factors elsewhere implicated in autocrine growth of mesothelioma cells and inactivates RASSF1, a gene silenced in MPM. Roles for ionising radiation, chemicals or genetic factors have also been suggested from the observation of sporadic MPM cases or animal studies. Genetic alterations in the tumour suppressor genes, P16/CDKN2A and neurofibromatosis 2 (NF2), are found both in human MPM and in asbestos-exposed Nf2-deficient mice. MPM is still of great international concern. Despite a ban on asbestos use in Western countries, the incidence of MPM is increasing, due to the long delay between asbestos exposure and diagnosis. Moreover, asbestos is still used in developing countries. The implication of other risk factors, especially SV40, supports a need for further research into MPM.}, } @article {pmid15668716, year = {2005}, author = {Hodgson, JT and McElvenny, DM and Darnton, AJ and Price, MJ and Peto, J}, title = {The expected burden of mesothelioma mortality in Great Britain from 2002 to 2050.}, journal = {British journal of cancer}, volume = {92}, number = {3}, pages = {587-593}, pmid = {15668716}, issn = {0007-0920}, mesh = {Adult ; Age Factors ; Aged ; Asbestos/*adverse effects ; Cohort Studies ; *Forecasting ; Humans ; Male ; Mesothelioma/*mortality ; Middle Aged ; Occupational Diseases/mortality ; Occupational Exposure ; Registries ; Risk Factors ; Time Factors ; United Kingdom/epidemiology ; }, abstract = {The British mesothelioma register contains all deaths from 1968 to 2001 where mesothelioma was mentioned on the death certificate. These data were used to predict the future burden of mesothelioma mortality in Great Britain. Poisson regression analysis was used to model male mesothelioma deaths from 1968 to 2001 as a function of the rise and fall of asbestos exposure during the 20th century, and hence to predict numbers of male deaths in the years 2002-2050. The annual number of mesothelioma deaths in Great Britain has risen increasingly rapidly from 153 deaths in 1968 to 1848 in 2001 and, using our preferred model, is predicted to peak at around 1950 to 2450 deaths per year between 2011 and 2015. Following this peak, the number of deaths is expected to decline rapidly. The eventual death rate will depend on the background level and any residual asbestos exposure. Between 1968 and 2050, there will have been approximately 90,000 deaths from mesothelioma in Great Britain, 65,000 of which will occur after 2001.}, } @article {pmid15657198, year = {2005}, author = {Greenberg, M}, title = {Changing trends in US mesothelioma incidence.}, journal = {Occupational and environmental medicine}, volume = {62}, number = {2}, pages = {134}, doi = {10.1136/oem.2004.018051}, pmid = {15657198}, issn = {1470-7926}, mesh = {Asbestos/*toxicity ; Carcinogens/*toxicity ; Humans ; Mesothelioma/*epidemiology ; Occupational Diseases/*epidemiology ; Pleural Neoplasms/*epidemiology ; United States/epidemiology ; }, } @article {pmid15654178, year = {2005}, author = {Hughes, RS}, title = {Malignant pleural mesothelioma.}, journal = {The American journal of the medical sciences}, volume = {329}, number = {1}, pages = {29-44}, doi = {10.1097/00000441-200501000-00007}, pmid = {15654178}, issn = {0002-9629}, mesh = {Asbestos/toxicity ; Humans ; Mesothelioma/diagnosis/*epidemiology/etiology/therapy ; Pleural Neoplasms/diagnosis/*epidemiology/etiology/therapy ; Polyomavirus Infections/complications ; Prognosis ; Risk Factors ; Simian virus 40/pathogenicity ; Tumor Virus Infections/complications ; }, abstract = {Malignant pleural mesothelioma is an uncommon tumor; only about 3000 cases are diagnosed annually in the United States. Cases were described early in the 20th century, but their relationship to asbestos exposure was not documented until 1960. Since then, the incidence has appeared to increase, and numerous epidemiologic studies have confirmed that exposure to asbestos in a variety of settings and occupations is the most significant risk factor for the development of malignant pleural mesothelioma. More recently, the oncogenic virus SV40 has also been implicated as a potential etiologic agent. Surgery, radiotherapy, and chemotherapy have each been used in the treatment of mesothelioma, but generally with little impact on survival. New directions in therapy include aggressive multimodality programs for potentially resectable patients and targeted therapies, including antifolates, antiangiogenesis agents, and drugs directed at epidermal growth factor receptor for the majority of patients presenting with unresectable disease.}, } @article {pmid15645436, year = {2005}, author = {Marinaccio, A and Montanaro, F and Mastrantonio, M and Uccelli, R and Altavista, P and Nesti, M and Costantini, AS and Gorini, G}, title = {Predictions of mortality from pleural mesothelioma in Italy: a model based on asbestos consumption figures supports results from age-period-cohort models.}, journal = {International journal of cancer}, volume = {115}, number = {1}, pages = {142-147}, doi = {10.1002/ijc.20820}, pmid = {15645436}, issn = {0020-7136}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; *Asbestos ; Cohort Studies ; Humans ; Italy ; Male ; Mesothelioma/*diagnosis/*mortality ; Middle Aged ; Models, Statistical ; Occupational Exposure ; Pleural Neoplasms/*diagnosis/*mortality ; Time Factors ; }, abstract = {Italy was the second main asbestos producer in Europe, after the Soviet Union, until the end of the 1980s, and raw asbestos was imported on a large scale until 1992. The Italian pattern of asbestos consumption lags on average about 10 years behind the United States, Australia, the United Kingdom and the Nordic countries. Measures to reduce exposure were introduced in the mid-1970s in some workplaces. In 1986, limitations were imposed on the use of crocidolite and in 1992 asbestos was definitively banned. We have used primary pleural cancer mortality figures (1970-1999) to predict mortality from mesothelioma among Italian men in the next 30 years by age-cohort-period models and by a model based on asbestos consumption figures. The pleural cancer/mesothelioma ratio and mesothelioma misdiagnosis in the past were taken into account in the analysis. Estimated risks of birth cohorts born after 1945 decrease less quickly in Italy than in other Western countries. The findings predict a peak with about 800 mesothelioma annual deaths in the period 2012-2024. Results estimated using age-period-cohort models were similar to those obtained from the asbestos consumption model.}, } @article {pmid15639718, year = {2005}, author = {Tsou, JA and Shen, LY and Siegmund, KD and Long, TI and Laird, PW and Seneviratne, CK and Koss, MN and Pass, HI and Hagen, JA and Laird-Offringa, IA}, title = {Distinct DNA methylation profiles in malignant mesothelioma, lung adenocarcinoma, and non-tumor lung.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {47}, number = {2}, pages = {193-204}, doi = {10.1016/j.lungcan.2004.08.003}, pmid = {15639718}, issn = {0169-5002}, mesh = {Adenocarcinoma/*genetics ; Carcinoma, Non-Small-Cell Lung/*genetics ; *DNA Methylation ; *DNA, Neoplasm ; Genes, Tumor Suppressor ; *Genetic Markers ; Humans ; Lung ; Lung Neoplasms/*genetics ; Mesothelioma/*genetics ; Sensitivity and Specificity ; Tumor Cells, Cultured ; }, abstract = {DNA methylation markers provide a powerful tool to make diagnoses based on genetic material obtained directly from tumors or from "remote" locations such as sputum, pleural fluid, or serum. In particular when limited cell numbers are available, amplifyable DNA markers can provide a very sensitive tool for cancer detection and classification. Malignant mesothelioma (MM), an aggressive cancer strongly associated with asbestos exposure, can be difficult to distinguish from adenocarcinoma of the lung when limited material is available. In an attempt to identify molecular markers for MM and adenocarcinoma, we examined the DNA methylation status of 14 loci. Analysis of methylation levels in 10 MM and 8 adenocarcinoma cell lines showed that methylation of APC was significantly elevated in adenocarcinoma compared to MM cell lines (P=0.0003), while methylation of CDH1 was higher in MM (P<0.02). Subsequent examination of the methylation status of the 14 loci in 6 MM and 7 adenocarcinoma primary tumors, which yielded similar methylation profiles, supported these observations. Comparison of methylation in MM cell lines and tumors versus non-tumor lung tissue indicated that APC exhibits less methylation in MM (P=0.003) while RASSF1, PGR1, ESR1, and CDH1 show more methylation in MM, the latter two showing the most significant difference between the two tissue types (P< or = 0.0001). Comparison of methylation in adenocarcinoma cell lines and tumors versus non-tumor lung tissue showed methylation of ESR1, PGR1 and RASSF1 to be significantly elevated in adenocarcinoma, with RASSF1 being most significant (P=0.0002). Thus, with the examination of 14 loci, we have identified 5 candidates that show potential for distinguishing between MM, adenocarcinoma and/or non-cancer lung. Our observations support the strong potential of methylation markers as tools for accurate diagnosis of neoplasms in and around the lung.}, } @article {pmid20067210, year = {2005}, author = {Wilczyńska, U and Szeszenia-Dabrowska, N}, title = {[Occupational cancers in Poland, 1995-2003].}, journal = {Medycyna pracy}, volume = {56}, number = {2}, pages = {113-120}, pmid = {20067210}, issn = {0465-5893}, mesh = {Carcinogens/toxicity ; Environmental Pollutants/toxicity ; Female ; Humans ; Incidence ; Male ; Neoplasms/*epidemiology/prevention & control ; Occupational Diseases/*epidemiology/prevention & control ; Occupational Exposure/*statistics & numerical data ; Occupational Medicine ; Occupations/*statistics & numerical data ; Peritoneal Neoplasms/epidemiology ; Poland/epidemiology ; Respiratory Tract Neoplasms/epidemiology ; Risk Factors ; Sex Distribution ; }, abstract = {BACKGROUND: The aim of this paper is to present current data on the incidence of occupational cancer in Poland.

MATERIALS AND METHODS: This work is based on the information collected from forms reporting cases of occupational diseases in 1995-2003, received by the Central Register of Occupational Diseases run by the Nofer Institute of Occupational Medicine, Łódź, Poland. During that period, 1124 cases of cancer were registered.

RESULTS: Occupational cancer was diagnosed in 125 people per year on the average. The occupational cancer cases made 1.4% of all occupational diseases. In individual years, the contribution of occupational cancer showed the upward trend. The most frequent tumor sites were: lung (51.6%), larynx (18.9%), pleura (7.6%), urinary bladder (6.0%), lymphatic and hemopoietic tissues (3.9%), skin (3.7%). Asbestos was specified as a causal factor of every third case (32.8% of reported cases) of occupational cancer: 38.9% of lung tumors, 25.6% of larynx tumors and all pleural mesotheliomas. Occupational exposure to polycyclic aromatic hydrocarbons and ionising radiation was responsible for 10.8% of tumors each. Polycydic aromatic hydrocarbons were recorded as a causal factor of 15.4% of pulmonary, 10.6% of laryngeal, 12.8% of dermal, and 11.4% of lymphatic and hemopoietic tissue tumors, while ionising radiation for 12.8% of pulmonary, 23.1% of dermal, and 22.7% of lymphatic and hemopoietic tissue cancers. Males formed the majority (90.5%) of patients with diagnosed occupational cancer. Pulmonary (52.7%) and laryngeal (20.1%) cancers were the most frequent tumors in men. Among women, pulmonary cancer also occupied the first place (41.1%) and was followed by pleural mesothelioma (21,5%).

CONCLUSIONS: The proportion of malignant tumors in the overall number of occupational diseases shows the upward trend. Due to long latency period of the disease, the recorded cases reflect exposures of long time ago.}, } @article {pmid15620609, year = {2005}, author = {Jaurand, MC}, title = {Mesothelioma pathogenesis, facts and expectations.}, journal = {Pathologie-biologie}, volume = {53}, number = {1}, pages = {41-44}, doi = {10.1016/j.patbio.2003.10.005}, pmid = {15620609}, issn = {0369-8114}, mesh = {Asbestos/*toxicity ; Humans ; Mesothelioma/epidemiology/etiology/*pathology ; South Africa/epidemiology ; }, abstract = {It is the merit of Dr J.C. Wagner and his co-workers to have triggered the research on mesothelioma, going back to 1960 when they published data demonstrating a relationship between mesothelioma occurrence and exposure to asbestos fibres in the Cape Province, in South Africa. From that time, epidemiological and toxicological investigations were performed in order to better define the occupational and environmental background of this pathology, to identify the fibre parameters accounting for the toxic effects, and to understand their mechanisms of action. Improvements in our knowledge in these areas benefited to health issues, by preventing risks associated with exposure to mineral fibres and by recognising the disease. Due to the actual progresses in the fields of biology and biotechnologies, the research on mesothelioma presently focuses on study of the mechanisms of mesothelial cell transformation, and on development of strategies to kill tumour cells. While mesothelioma benefited to fibre toxicology and allowed to improve the management health related issue, it would be a just return if the present advances in different scientific areas will permit a rapid eradication of the disease.}, } @article {pmid15605578, year = {2004}, author = {Ameille, J and Ruffié, P and Bergeret, A}, title = {[Asbestos-related occupational cancers].}, journal = {La Revue du praticien}, volume = {54}, number = {15}, pages = {1649-1659}, pmid = {15605578}, issn = {0035-2640}, mesh = {Asbestos/*adverse effects ; Environmental Exposure/adverse effects ; France ; Humans ; Lung Neoplasms/*etiology/prevention & control ; Mesothelioma/etiology ; Occupational Diseases/*etiology/prevention & control ; Pleural Neoplasms/etiology ; Workers' Compensation ; }, abstract = {Due to its remarkable physical properties asbestos has been widely used in the industry. It is estimated that 25% of present French retired workers have been occupationally exposed to asbestos. A causal relationship between asbestos exposure and respiratory cancers is established since 1955 for lung cancer, and since 1960 for pleural mesothelioma. A causal relationship is also demonstrated for peritoneal and pericardic mesotheliomas, and strongly suspected for laryngeal cancers. It is estimated that occupational exposure to asbestos could be responsible for 5 to 20% of lung cancers and 80 to 90% of pleural mesothelioma, in men, in industrialized countries. The risk of cancer is positively correlated to cumulated exposure. No threshold has been demonstrated below which there is no increased risk of respiratory cancer.}, } @article {pmid15605577, year = {2004}, author = {Pairon, JC and de Clavière, C}, title = {[Main carcinogens and epidemiology of occupational cancers].}, journal = {La Revue du praticien}, volume = {54}, number = {15}, pages = {1640-1648}, pmid = {15605577}, issn = {0035-2640}, mesh = {Carcinogens/*adverse effects ; France/epidemiology ; Humans ; Neoplasms/*chemically induced/*epidemiology ; Occupational Diseases/*chemically induced/*epidemiology ; }, abstract = {Recent epidemiological studies estimate that the number of occupational cancers is high, as more than 3800 and up to 7000 cases occur each year in France in men. Attribuable fraction to occupational factors varies widely from one site of cancer to another. Respiratory cancers (lung and pleura) are by far the most frequent of occupational cancers with an attributable fraction of 13 to 29% for lung cancer in men according to the international literature, and an attributable fraction of 85% for pleural mesothelioma. Previous occupational exposure to asbestos is the most frequent occupational exposure for these cancers. Many occupational agents have been identified as etiological factors of cancer for different sites. Attention should be paid to these aetiologies and primary prevention programmes should be held at work in order to avoid residual occupational exposure.}, } @article {pmid15595204, year = {2004}, author = {Merler, E and Roberti, S and Gioffrè, F}, title = {[The standard of the scientific communication and deaths attributable to exposure to asbestos in the cohort quoted by the Professor E. Gaffuri].}, journal = {La Medicina del lavoro}, volume = {95}, number = {5}, pages = {412}, pmid = {15595204}, issn = {0025-7818}, mesh = {Asbestosis/etiology/*mortality ; Cohort Studies ; Follow-Up Studies ; Humans ; Italy ; Lung Neoplasms/*etiology/*mortality ; Mesothelioma/*etiology/*mortality ; Occupational Exposure/*adverse effects ; Time Factors ; }, } @article {pmid15595201, year = {2004}, author = {Tessari, R and Canova, C and Simonato, L}, title = {[Epidemiological investigation on the health status of employees in two factories manufacturing and repairing railway rolling stock: a historical perspective study of mortality].}, journal = {La Medicina del lavoro}, volume = {95}, number = {5}, pages = {381-391}, pmid = {15595201}, issn = {0025-7818}, mesh = {Asbestos/*adverse effects ; Asbestosis/*epidemiology/mortality ; Cohort Studies ; Confidence Intervals ; Data Interpretation, Statistical ; Follow-Up Studies ; Humans ; Italy/epidemiology ; Lung Neoplasms/*epidemiology/mortality ; Mesothelioma/*epidemiology/mortality ; Occupational Diseases/*mortality ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*epidemiology/mortality ; Prospective Studies ; *Railroads ; Risk Factors ; }, abstract = {BACKGROUND: Epidemiological studies of cancer risk due to occupational exposure to asbestos in production and repair of railway rolling stock has so far given consistent results for mesothelioma, but conflicting evidence for lung cancer.

OBJECTIVES: The main purpose of this study was to investigate risk for mesothelioma and lung cancer in relation to estimated patterns of exposure in the occupational environment of railway rolling stock manufacture and repair.

METHODS: A historical prospective study approach was adopted. The mortality experience of the study population was compared to that of the population of the Veneto Region. Two historical cohorts of workers employed in two plants manufacturing and repairing railway coaches were followed up for mortality. A total of 1,621 workers were enrolled in the study from the first factory, and 1,190 from the second.

RESULTS: An elevation of both pleural mesothelioma and lung cancer was reported in the two factories with SMRs of 21.52 (CI 95%=1.64-32.29) and 6.46 (CI 95%=1.33-18.88), and 1.26 (CI 95%=1.01-1.54) and 1.18 (CI 95%=0.81-1.66) respectively. The two excesses however showed different patterns in relation to historical exposure estimates, which appear to correlate with mesotheliomas but not with lung cancer. An elevation of mortality for non-neoplastic respiratory diseases was associated with employment during periods when it was estimated that exposure was at higher levels in one of the two firms.

CONCLUSIONS: The results confirm the high carcinogenic risk deriving from asbestos exposure, although inconsistencies were found between target organs in relation to exposure estimates, and the existence of time periods in production in which cancer risk was different.}, } @article {pmid15595200, year = {2004}, author = {Bianchi, C and Bianchi, T and Ramani, L}, title = {[Malignant mesothelioma of the pleura among women].}, journal = {La Medicina del lavoro}, volume = {95}, number = {5}, pages = {376-380}, pmid = {15595200}, issn = {0025-7818}, mesh = {Age Factors ; Aged ; Aged, 80 and over ; Asbestos ; Asbestosis/*complications/pathology ; Autopsy ; Female ; Humans ; Italy/epidemiology ; Lung/pathology ; Mesothelioma/*epidemiology/etiology/pathology ; Middle Aged ; Pleura/pathology ; Pleural Neoplasms/*epidemiology/etiology/pathology ; Sex Factors ; Time Factors ; }, abstract = {BACKGROUND: The epidemiological features of mesothelioma among women differ from those observed among men.

OBJECTIVES: To trace the outline of pleural mesothelioma among women in the Monfalcone area, Italy.

METHODS: Thirty-three malignant mesotheliomas of the pleura observed in female patients at the Hospital of Monfalcone, Italy, in the period 1979-2002 were reviewed. The diagnosis was based on/or confirmed by necropsy findings in 30 cases. Occupational and social histories were obtained from the patients themselves or from their relatives by personal or telephone interviews. In 29 necropsy cases thoracic cavities were examined for the presence of pleural plaques. Routine lung section were examined for asbestos bodies in 30 cases. In 21 cases asbestos bodies were isolated and counted after chemical digestion of lung tissue.

RESULTS: The age of the patients ranged between 48 and 89 years (mean 72.85, median 73.00). All the patients had histories of exposure to asbestos, single in 25 cases and mixed in 8. Exposure at home due to cleaning of work clothes was the most frequent type of exposure. Various patients had been exposed in non-asbestos text industries (cotton mills). Unusual types of exposure occurred in some cases (distillery, small sodium carbonate factory, starch factory). The latency periods (time intervals elapsed between first exposure to asbestos and diagnosis of the tumour), calculated in 23 cases, ranged from 34 to 62 years. Pleural plaques were found in 21 cases. Twelve patients showed asbestos bodies on routine lung sections. The asbestos body burden ranged between only a few bodies and 92,000/g dried tissue.

CONCLUSIONS: In contrast with other series of mesothelioma among women, all the present cases were attributable to asbestos. The detection of objective signs of exposure (pleural plaques, lung asbestos bodies) played a key role in attribution.}, } @article {pmid15592515, year = {2005}, author = {Suzuki, M and Toyooka, S and Shivapurkar, N and Shigematsu, H and Miyajima, K and Takahashi, T and Stastny, V and Zern, AL and Fujisawa, T and Pass, HI and Carbone, M and Gazdar, AF}, title = {Aberrant methylation profile of human malignant mesotheliomas and its relationship to SV40 infection.}, journal = {Oncogene}, volume = {24}, number = {7}, pages = {1302-1308}, doi = {10.1038/sj.onc.1208263}, pmid = {15592515}, issn = {0950-9232}, support = {5U01CA8497102/CA/NCI NIH HHS/United States ; P50CA70907/CA/NCI NIH HHS/United States ; R0-1 CA92657/CA/NCI NIH HHS/United States ; }, mesh = {Cell Line, Tumor ; *DNA Methylation ; Epithelium/metabolism/virology ; *Genes, Tumor Suppressor ; Humans ; Mesothelioma/*genetics/metabolism/*virology ; Polyomavirus Infections/*genetics/metabolism ; *Simian virus 40 ; Tumor Virus Infections/*genetics/metabolism ; }, abstract = {Malignant mesothelioma (MM) is associated with asbestos exposure and the presence of SV40 viral sequences. Recently, we reported that SV40 infection of human mesothelial cells (HM) causes aberrant methylation of the tumor suppressor gene (TSG) RASSF1A. We investigated methylation of 12 genes by methylation-specific PCR in 63 MMs, six MM cell lines, and two foci of SV40-infected HM. Methylation percentages of the tested genes ranged from 3 to 65%. The frequencies of HPP1, RASSF1A, Cyclin D2, and RRAD methylation, and the value of the methylation index, were significantly higher in SV40 sequence-positive MMs than in SV40-negative MMs. Methylation of TMS1 and HIC-1 was associated with shortened survival. SV40-infected HM showed progressive aberrant methylation of seven genes (RASSF1A, HPP1, DcR1, TMS1, CRBP1, HIC-1, and RRAD) during serial passage. Our results demonstrate a relationship between SV40 and methylation of multiple genes in MM, indicating that the virus plays a role in the pathogenesis of MM.}, } @article {pmid15584446, year = {2004}, author = {Muzi, G and dell'Omo, M and Murgia, N and Abbritti, G}, title = {[Chemical pollution of indoor air and its effects on health].}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {26}, number = {4}, pages = {364-369}, pmid = {15584446}, issn = {1592-7830}, mesh = {*Air Pollutants/adverse effects ; *Air Pollution, Indoor/adverse effects ; Asbestos/adverse effects ; Carcinogens, Environmental/adverse effects ; Cardiovascular Diseases/etiology ; Humans ; Mineral Fibers/adverse effects ; *Occupational Health ; Organic Chemicals/adverse effects ; Particle Size ; Respiratory Tract Diseases/etiology ; Risk Factors ; Tobacco Smoke Pollution/adverse effects ; Workplace ; World Health Organization ; }, abstract = {Many studies have demonstrated how exposure to chemical pollutants in indoor air has adverse effects on health and comfort. Volatile organic compounds (VOCs), formaldehyde, ozone, particulates, fibres and environmental tobacco smoke have all been implicated. VOCs include a wide range of chemical substances which irritate mucosa. Many are neurotoxic and some are suspected or known to be carcinogenic e.g. benzene. Formaldehyde, the simplest and most common aldehyde in indoor air, is a powerful irritant to the skin, eyes, nose and upper airways. Given its close association with nasal-pharyngeal tumours, it has recently been classified as a certain carcinogen for humans. Exposure to ozone may cause airway irritation and inflammation, reduce the ventilation function and increase reversible bronchial reactivity. In the general population it increases the mortality rate and the number of hospital admissions for respiratory diseases. Airborne particles, a mixture of organic and inorganic substances, are powerful irritants for the eyes and mucosa and can cause adverse cardiovascular effects. Apart from indoor environments, exposure to asbestos fibres has been associated with an increased risk of respiratory diseases such as pneumoconiosis lung cancer and mesothelioma. Synthetic mineral fibres cause transient irritation and inflammation of the skin, eyes and upper airways. Recent observations have confirmed that exposure to environmental tobacco smoke, which is widespread in workplaces, increases the risk of lung cancer, irritative respiratory and ocular symptoms and cardiovascular diseases.}, } @article {pmid15570336, year = {2004}, author = {Smartt, P}, title = {Mortality, morbidity, and asbestosis in New Zealand: the hidden legacy of asbestos exposure.}, journal = {The New Zealand medical journal}, volume = {117}, number = {1205}, pages = {U1153}, pmid = {15570336}, issn = {1175-8716}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestosis/economics/epidemiology/*mortality ; Cardiovascular Diseases/mortality ; Cause of Death ; Hospital Costs ; Humans ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/mortality ; Middle Aged ; Morbidity ; Mortality/trends ; New Zealand/epidemiology ; Occupations ; Respiratory Tract Diseases/economics/mortality ; }, abstract = {AIMS: To examine the morbidity and mortality patterns of patients with asbestosis in New Zealand to determine (more fully) the overall health impact of past exposure to asbestos.

METHODS: Individual mortality, cancer and hospital records for all New Zealand men diagnosed with asbestosis between 1974-2001 were examined. Mortality data were analysed for time trends, cause of death, and occupation. Trends for patients diagnosed with asbestosis were compared with those diagnosed with lung cancer. Hospital discharge data for men with asbestosis were examined to determine reasons for hospitalisation, resource utility, and recent hospitalisation trends.

RESULTS: Death rates for New Zealand males dying with asbestosis increased between 1974-1999. Only 17% of deaths of males dying with asbestosis were directly attributed to this cause; the remainder were attributed to other non-malignant and malignant respiratory disease. Deaths from asbestos-related lung disease were grossly underestimated. Death certificates of men dying with asbestosis were found in all major occupational groups. Trends in hospital discharges may provide additional information for the overall modelling of the current epidemic of asbestos related disease.

CONCLUSION: The number of men dying with asbestosis in NZ has increased in line with mesothelioma. There is some indication that asbestosis prevalence may have peaked for the most serious cases of asbestosis. Some level of asbestos exposure, as indicated by asbestosis, may be present in all major occupational groups.}, } @article {pmid15569059, year = {2004}, author = {Serio, G and Scattone, A and Gentile, M and Nazzaro, P and Pennella, A and Buonadonna, AL and Pollice, L and Musti, M}, title = {Familial pleural mesothelioma with environmental asbestos exposure: losses of DNA sequences by comparative genomic hybridization (CGH).}, journal = {Histopathology}, volume = {45}, number = {6}, pages = {643-645}, doi = {10.1111/j.1365-2559.2004.01941.x}, pmid = {15569059}, issn = {0309-0167}, mesh = {Adult ; Asbestos/*poisoning ; Chromosome Aberrations ; DNA, Neoplasm/genetics ; Environmental Exposure/*adverse effects ; Family Health ; Female ; Humans ; Mesothelioma/etiology/*genetics ; Nucleic Acid Hybridization/methods ; Pleural Neoplasms/etiology/*genetics ; }, } @article {pmid15560429, year = {2004}, author = {McCulloch, J and Tweedale, G}, title = {Double standards: the multinational asbestos industry and asbestos-related disease in South Africa.}, journal = {International journal of health services : planning, administration, evaluation}, volume = {34}, number = {4}, pages = {663-679}, doi = {10.2190/F06D-LE93-M6LH-XJ0B}, pmid = {15560429}, issn = {0020-7314}, mesh = {Asbestos/*history/standards ; Asbestosis/*history/prevention & control ; Decision Making, Organizational ; Government Regulation/*history ; History, 19th Century ; History, 20th Century ; Humans ; Internationality ; Mesothelioma/history/prevention & control ; Mining/ethics/*history/organization & administration ; Occupational Exposure/*history/prevention & control/standards ; South Africa ; United Kingdom ; }, abstract = {This study documents and contrasts the development of knowledge about asbestos-related disease (ARD) in South Africa and the United Kingdom. It also contributes to the globalization debate by exploring corporate decision-making in a multinational industry. Between the 1930s and 1960s, the leading U.K. asbestos companies developed a sophisticated knowledge of ARD, though in South Africa, where the leading companies such as Turner & Newall and Cape Asbestos owned mines, there was little attempt to apply this knowledge. Asbestos mines (and their environments) in South Africa were uniquely dusty and ARD was rife. Social and political factors in South Africa, especially apartheid, allowed these companies to apply double standards, even after 1960 when the much more serious hazard of mesothelioma was identified. This shows the need for greater regulation of multinationals. Because of the lack of such regulation in the early 1960s, an opportunity was lost to prevent the current high morbidity and mortality of ARD both in South Africa and worldwide.}, } @article {pmid15559057, year = {2004}, author = {Paul, S and Neragi-Miandoab, S and Jaklitsch, MT}, title = {Preoperative assessment and therapeutic options for patients with malignant pleural mesothelioma.}, journal = {Thoracic surgery clinics}, volume = {14}, number = {4}, pages = {505-16, ix}, doi = {10.1016/j.thorsurg.2004.06.008}, pmid = {15559057}, issn = {1547-4127}, mesh = {Combined Modality Therapy ; Diagnostic Imaging ; Humans ; Mesothelioma/*diagnosis/*therapy ; Neoplasm Staging ; Patient Care Planning ; Pleural Neoplasms/*diagnosis/*therapy ; Thoracic Surgery, Video-Assisted ; }, abstract = {Prompt medical evaluation and aggressive treatment can lead to prolonged survival or successful palliation of symptoms for patients with malignant pleural mesothelioma, but the window for implementing treatment is short. Clinical recognition of the cancer is confounded by numerous factors, including long latency between exposure to asbestos and expression of the disease, nonspecific nature of the presenting symptoms, rarity of the disease, a lack of experience in clinical diagnosis, and rapidly deteriorating clinical course after diagnosis. Heightened clinical suspicion and proper patient selection through accurate staging and pathologic identification are paramount to defining and delivering therapy for this rare, lethal cancer.}, } @article {pmid15559054, year = {2004}, author = {Godleski, JJ}, title = {Role of asbestos in etiology of malignant pleural mesothelioma.}, journal = {Thoracic surgery clinics}, volume = {14}, number = {4}, pages = {479-487}, doi = {10.1016/S1547-4127(04)00111-2}, pmid = {15559054}, issn = {1547-4127}, mesh = {Asbestos/*toxicity ; Environmental Exposure/adverse effects ; Humans ; Mesothelioma/*etiology ; Occupational Exposure/adverse effects ; Pleural Neoplasms/*etiology ; }, abstract = {The evidence presented in this article demonstrates that asbestos fibers may be genotoxic to mesothelial cells through their distinctive structure and chemistry and through their interactions with complex cellular response mechanisms. Reactive oxygen and nitrogen species play a key role. Understanding the balance between these complex mechanisms that permit neoplastic transformation and facilitate the proliferation of tumor cells is the focus of current investigation in the development of mesothelial malignancy. In human disease, the persistence of asbestos fibers in the lung and pleural tumor is a critical feature that links the exposure to asbestos with the development of disease.}, } @article {pmid15559053, year = {2004}, author = {Zellos, L and Christiani, DC}, title = {Epidemiology, biologic behavior, and natural history of mesothelioma.}, journal = {Thoracic surgery clinics}, volume = {14}, number = {4}, pages = {469-77, viii}, doi = {10.1016/j.thorsurg.2004.06.011}, pmid = {15559053}, issn = {1547-4127}, mesh = {Asbestos/*toxicity ; Environmental Exposure/adverse effects ; Humans ; Mesothelioma/*epidemiology/pathology ; Neoplasm Staging ; Occupational Exposure/adverse effects ; Pleural Neoplasms/*epidemiology/pathology ; Prognosis ; Risk Factors ; Time Factors ; }, abstract = {Malignant pleural mesothelioma has a well described natural history but poorly defined pathogenesis. It is strongly associated with asbestos exposure. A predominantly locally invasive disease, the success of more aggressive life-prolonging therapies has increased the potential for the development of distant metastases in survivors. Recently described new risk factors may increase the incidence of this disease in future generations, underscoring the need for a more in-depth understanding of its pathobiology. This article reviews the current body of knowledge about the occurrence, distribution, presentation, and natural history of malignant pleural mesothelioma.}, } @article {pmid15559050, year = {2004}, author = {Kukreja, J and Jaklitsch, MT and Wiener, DC and Sugarbaker, DJ and Burgers, S and Baas, P}, title = {Malignant pleural mesothelioma: overview of the North American and European experience.}, journal = {Thoracic surgery clinics}, volume = {14}, number = {4}, pages = {435-445}, doi = {10.1016/j.thorsurg.2004.06.009}, pmid = {15559050}, issn = {1547-4127}, mesh = {Combined Modality Therapy ; Europe/epidemiology ; Humans ; Incidence ; Mesothelioma/diagnosis/*epidemiology/therapy ; Neoplasm Staging ; North America/epidemiology ; Pleural Neoplasms/diagnosis/*epidemiology/therapy ; Prognosis ; Survival Rate ; }, abstract = {MPM is an uncommon disease with limited treatment options. Early diagnosis, a standardized staging system, early referral to centers experienced in MPM, and efforts to develop collaborative multicenter trials are essential to improving treatment for patients with MPM. Efforts to manage this malignancy, which is projected to peak in the twenty-first century, constitute an important international health concern, particularly because the use of asbestos, despite successful regulatory efforts in many parts of the world, continues unabated in others.}, } @article {pmid15547739, year = {2004}, author = {Cardile, V and Proietti, L and Panico, A and Lombardo, L}, title = {Nitric oxide production in fluoro-edenite treated mouse monocyte-macrophage cultures.}, journal = {Oncology reports}, volume = {12}, number = {6}, pages = {1209-1215}, pmid = {15547739}, issn = {1021-335X}, mesh = {Animals ; Asbestos, Amphibole/*toxicity ; Cell Line ; Dose-Response Relationship, Drug ; Image Processing, Computer-Assisted ; Immunohistochemistry ; Lipopolysaccharides/pharmacology ; Macrophages/*drug effects/metabolism ; Mice ; Monocytes/*drug effects/metabolism ; Nitric Oxide/*biosynthesis ; Nitric Oxide Synthase/drug effects/metabolism ; Nitric Oxide Synthase Type II ; Time ; }, abstract = {In the present study, we investigated the involvement of NO in the cytotoxic and genotoxic effects caused by fluoro-edenite in mouse monocyte-macrophage cell line J774. Fluoro-edenite is a new asbestos-like amphibole present in the benmoreitic lavas recently extracted from stone quarries in Biancavilla, a village located in the Etnean Volcanic Complex (Catania, Italy) of eastern Sicily, in which an epidemiological survey evidenced a cluster of cases of the mortality due to pleural mesothelioma. Fluoro-edenite appears as a probable carcinogenic agent. Nitrite and nitrate concentration (NO) in the supernatant was quantified by colorimetric assay based on the Griess reaction and iNOS (inducible nitric oxide synthetase) expression was determined by immunostaining in mouse monocyte-macrophage cell line J774 treated with different concentrations of fluoro-edenite (5, 50 and 100 microg/ml) for 24, 48, 72 and 96 h. Parallel experiments were performed treating the cultures also with lipopolysaccharides (LPS), used as inflammation-inducing molecule. In our experimental conditions, fluoro-edenite did not modify the level of NO and the expression of iNOS at the experimental used concentrations for 24, 48 and 72 h. These parameters were significantly modified at the higher doses (50 and 100 microg/ml) of fluoro-edenite for 96 h and were further more increased, in concentration- and time-dependent manner, when cell cultures were treated with fluoro-edenite and LPS. These findings provide convincing evidence that NO is involved in the fluoro-edenite-induced cytotoxicity and geno-toxicity in mouse monocyte-macrophage cell line J774 when the fiber remain for longer times and particularly in cultures treated with LPS, demonstrating that inflammatory disorders appear to increase the risk for lung cancer induced by fluoro-edenite probably by the involvement of NO.}, } @article {pmid15545953, year = {2004}, author = {Saint-Georges, F and Mulliez, P and Darras, A and Smith, M}, title = {[Spontaneous pneumothorax revealing malignant pleural mesothelioma. Three case reports].}, journal = {Revue de pneumologie clinique}, volume = {60}, number = {4}, pages = {229-233}, doi = {10.1016/s0761-8417(04)72105-7}, pmid = {15545953}, issn = {0761-8417}, mesh = {Adult ; Aged ; Humans ; Male ; Mesothelioma/*complications ; Pleural Neoplasms/*complications ; Pneumothorax/*etiology ; }, abstract = {Spontaneous pneumothorax is an uncommon inaugural presentation of malignant pleural mesothelioma. We report three cases in men aged 65, 30 and 76 years. The diagnosis was suggested at medical imaging and was confirmed at histological analysis of biopsies obtained by thoracoscopy in two patients and thoracotomy in one. The first patient (age 65 years) died two months after the initial diagnosis. The second patient (age 30 years) was alive 40 months after 15 chemotherapy cycles using a platinim-gemcitabine combination. Complete tumor response was achieved in the third patient (age 76 years) after 9 chemotherapy cycles with the same combination. Since mid-term prognosis is fatal for this type of tumor, we propose thoracoscopy in all patients over 30 years who develop spontaneous pneumothorax with no morphological features increasing the risk of pneumothorax, and particularly in patients with asbestos exposure.}, } @article {pmid15540627, year = {2004}, author = {Kishimoto, T and Ozaki, S and Kato, K and Nishi, H and Genba, K}, title = {Malignant pleural mesothelioma in parts of Japan in relationship to asbestos exposure.}, journal = {Industrial health}, volume = {42}, number = {4}, pages = {435-439}, doi = {10.2486/indhealth.42.435}, pmid = {15540627}, issn = {0019-8366}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Case-Control Studies ; Female ; Hospitalization ; Humans ; Japan/epidemiology ; Male ; Mesothelioma/*epidemiology/*etiology ; Middle Aged ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*epidemiology/*etiology ; Survival Analysis ; Time Factors ; }, abstract = {Malignant pleural mesothelioma is induced by asbestos exposure. Many reports have described this situation in America and European countries, but a few have been published in Japan. In this study malignant pleural mesothelioma cases in hospitals located in an area facing the Seto Inland Sea were evaluated. A total of 106 patients were examined with 100 patients having had occupational exposure to asbestos and 6 patients without such histories of asbestos exposure. Ninety seven were male and 9 were female. Ages ranged from 41 to 87 yr with mean of 64.8+/-5.3 yr. Thirty seven cases showed epithelial type of tumor, 25 biphasic type and 15 showed sarcomatous. The remaining 23 cases had insufficient evidence for typing the tumor. The mean survival rate for all cases was 9.2+/-11.6 months. Fifty-one patients had occupational histories of shipyard work, 16 patients worked in asbestos cement piping, and the remainder were employed in miscellaneous jobs related asbestos exposure. The duration of asbestos exposure ranged up to 20 yr or longer with the mean of 17.2+/-8.9 yr and the average latent period for the occurrence of malignant pleural mesothelioma was more than 31 yr with the mean of 37.0+/-13.3 yr. Quantification of asbestos bodies in the lungs indicated a high concentration in most patients and the major types of asbestos fibers were crocidolite and amosite. Six cases appeared after exposure to chrysotile. These results indicated that ninety four percent of malignant pleural mesothelioma appeared due to the exposure to asbestos including crocidolite and amosite. The remainder may be blamed on exposure to chrysotile.}, } @article {pmid15536279, year = {2004}, author = {Pasetto, R and Bruni, B and Bruno, C and Cauzillo, G and Cavone, D and Convertini, L and De Mei, B and Marconi, A and Montagano, G and Musti, M and Paoletti, L and Comba, P}, title = {[Pleural mesothelioma and environmental exposure to mineral fibres: the case of a rural area in the Basilicata region, Italy].}, journal = {Annali dell'Istituto superiore di sanita}, volume = {40}, number = {2}, pages = {251-265}, pmid = {15536279}, issn = {0021-2571}, mesh = {Asbestos/*adverse effects ; Asbestos, Amphibole/*adverse effects ; Environmental Exposure/*adverse effects ; Humans ; Italy ; Mesothelioma/epidemiology/*etiology ; Mineral Fibers/adverse effects ; Pleural Neoplasms/epidemiology/*etiology ; Risk Assessment ; Rural Population ; }, abstract = {The main aspects of the sites characterized by environmental exposure to mineral asbestiform fibres are described. Several adverse health effects including high incidence of pleural mesothelioma are reported. The average concentration of airborne fibres is generally low but it rises significantly in association with mechanical disturb of materials with fibres. Multiple sources of exposure have been identified, fibres can be found in the soil and in many materials locally used, mainly in buildings. Three mesothelioma cases were observed in a small rural area of the Basilicata region (Italy). Two of them had a possible occupational exposure to asbestos, the third had a proved environmental exposure to tremolite. This fibre, found in the area, is the same observed in two of the three biological samples analysed.}, } @article {pmid15534864, year = {2004}, author = {Nygren, J and Suhonen, S and Norppa, H and Linnainmaa, K}, title = {DNA damage in bronchial epithelial and mesothelial cells with and without associated crocidolite asbestos fibers.}, journal = {Environmental and molecular mutagenesis}, volume = {44}, number = {5}, pages = {477-482}, doi = {10.1002/em.20066}, pmid = {15534864}, issn = {0893-6692}, mesh = {Apoptosis ; Asbestos, Crocidolite/*toxicity ; Bronchi/*drug effects ; DNA Damage/*drug effects ; Epithelial Cells/*metabolism/pathology ; Epithelium/*metabolism/pathology ; Humans ; Necrosis ; }, abstract = {Mesothelioma is induced almost exclusively by exposure to asbestos fibers. We have investigated whether the induction of DNA damage in human bronchial epithelial BEAS 2B cells and human mesothelial MeT 5A cells by crocidolite asbestos (2 microg/cm2) requires the presence of asbestos fibers in the cells. DNA damage was measured microscopically by the Comet assay, and the presence of fibers in the same cells was assessed using bright-field illumination. After treatment times of 6-72 hr, damage levels were, on the average, two times higher in cells with fibers than in cells without fibers. It was further found that DNA damage decreased with time in BEAS 2B cells both with and without fibers. No decrease in damage with time was seen in MeT 5A cells, suggesting that these mesothelial cells repair the initial damage poorly, lack induction of protective systems, or constantly produce high levels of damaging species. Our results indicate that crocidolite-treated human mesothelial MeT 5A and bronchial epithelial BEAS 2B cells show an elevated level of DNA damage if they contain a fiber. In comparison with epithelial BEAS 2B cells, mesothelial MeT 5A cells have more DNA damage after the crocidolite treatment and the damage is more persistent.}, } @article {pmid15532964, year = {2004}, author = {Riboldi, L and Mensi, C and Giordano, S and Canti, Z and Chiappino, G}, title = {[Malignant mesothelioma of the pleura in a worker with brief atypical exposure to chrysotile asbestos].}, journal = {La Medicina del lavoro}, volume = {95}, number = {4}, pages = {320-324}, pmid = {15532964}, issn = {0025-7818}, mesh = {Aged ; Asbestos, Serpentine/*adverse effects ; Humans ; Male ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*etiology ; Time Factors ; }, abstract = {BACKGROUND: The appearance of malignant mesothelioma in workers exposed to asbestos dusts even for relatively short periods of time is amply demonstrated in the literature. The workers however were usually exposed to amphiboles in jobs well known as involving exposure, that are characterized by high levels of dusts.

OBJECTIVES: To describe a clinical case of pleural mesothelioma that occurred in a patient exposed to chrysotile, in a job (driver) that cannot be directly linked to such high exposure, and which moreover he only did for a few months.

METHODS: The clinical history was reconstructed by analyzing the clinical files of the hospital admittances from May 2002 to August 2003, during which the patient underwent radiological examinations (chest x-rays, chest and abdomen TC), cytological examination of the pleural fluid, videothoracoscopic surgery with histological examination (including immunohistochemical coloration) of the tissue taken in biopsy. The job history, as well as any possible non-occupational exposures to asbestos, was examined via a standardised questionnaire, which the patient himself answered, as used in the Lombardy Mesothelioma Register, in operation at the "Clinica del Lavoro" in Milan.

RESULTS: Examination of all clinical files confirmed the diagnosis of malignant pleural mesothelioma. Analysis of job history was found appropriate for defining as certain an occupational aetiology due to inhalation of asbestos fibres which occurred for few months as a truck driver in a chrysotile mine.}, } @article {pmid15532871, year = {2004}, author = {Menegozzo, M and Trinca, S and Cammino, F and Mastrantonio, M and Menegozzo, S and Sturchio, A and Comba, P}, title = {[Geographical distribution of mortality from malignant pleural neoplasms and of former asbestos-exposed workers in the Campania Region].}, journal = {Epidemiologia e prevenzione}, volume = {28}, number = {3}, pages = {150-155}, pmid = {15532871}, issn = {1120-9763}, mesh = {Asbestos/*adverse effects ; Female ; Humans ; Italy/epidemiology ; Male ; Occupational Diseases/*mortality ; Occupational Exposure/*statistics & numerical data ; Pleural Neoplasms/*mortality ; }, abstract = {AIM: The purpose of the present paper is to describe the geographical distribution at municipality level of mortality from malignant pleural neoplasms in the Campania Region, along with the distribution of former asbestos-exposed workers. A GIS (Geographical Information System) application has been developed to integrate exposure and mortality data.

STUDY DESIGN: The number of asbestos workers by municipality has been estimated by merging data provided by the National Institute for Insurance against Occupational Accidents (INAIL), the Ministry of Labour and an association of formerly exposed workers (AUSER Flegrea). The number of deaths from malignant pleural neoplasms by municipality has been derived from published studies regarding two consecutive periods: 1988-1994 and 1995-1997.

RESULTS: In the first period most deaths occurred in areas with a high number of formerly exposed asbestos workers, whilst in the second period mesothelioma mortality increased extending to other areas without registered exposed workers.

CONCLUSION: This finding may be attributable to the presence of atypical occupational exposures, not reported by the current information systems, or to environmental, non occupational exposure patterns.}, } @article {pmid15516678, year = {2004}, author = {Melloni, B and Monteil, J and Vincent, F and Bertin, F and Gaillard, S and Ducloux, T and Verbeke, S and Maubon, A and Vandroux, JC and Bonnaud, F}, title = {Assessment of 18F-fluorodeoxyglucose dual-head gamma camera in asbestos lung diseases.}, journal = {The European respiratory journal}, volume = {24}, number = {5}, pages = {814-821}, doi = {10.1183/09031936.04.00004504}, pmid = {15516678}, issn = {0903-1936}, mesh = {Adult ; Aged ; Biopsy ; False Positive Reactions ; *Fluorodeoxyglucose F18 ; Gamma Cameras/*standards ; Humans ; Lung Neoplasms/*diagnostic imaging ; Mesothelioma/*diagnostic imaging ; Middle Aged ; Pleural Diseases/diagnostic imaging ; Retrospective Studies ; Tomography, Emission-Computed ; Tomography, X-Ray Computed ; }, abstract = {The purpose of this study was to evaluate the performance of 18F-fluorodeoxyglucose (18FDG) imaging via coincidence detection emission tomography (CDET) in identifying malignant lesions in subjects exposed to asbestos. A total of 30 patients exposed to asbestos underwent 18FDG-CDET between January 2000 and June 2003. A CDET scan of the thorax and abdomen was performed 60 min after injection of 18FDG in fasting patients, and results were obtained in slices in three axes. The CDET results were compared to those from computed tomography (CT), and pleural or surgical biopsy in patients with positive 18FDG-CDET results. All primary malignant mesotheliomas accumulated 18FDG (n=6), and, in two patients, CDET findings were superior to those of CT, allowing early detection. In two cases, lung carcinomas with malignant pleural effusion were also detected. There were five false positive CDET results: three unilateral pleural thickening, one rounded atelectasis, and one benign lung nodule. All patients with pleural plaques showed no significant 18FDG uptake. Malignant diseases were detected by 18FDG-CDET imaging with a sensitivity of 89% and specificity of 71%. Coincidence detection emission tomography can identify malignant mesothelioma in selected subjects exposed to asbestos. Coincidence detection emission tomography appears to be a useful noninvasive method for the follow-up of subjects with exposure risk of asbestosis.}, } @article {pmid15513907, year = {2004}, author = {Ghio, AJ and Churg, A and Roggli, VL}, title = {Ferruginous bodies: implications in the mechanism of fiber and particle toxicity.}, journal = {Toxicologic pathology}, volume = {32}, number = {6}, pages = {643-649}, doi = {10.1080/01926230490885733}, pmid = {15513907}, issn = {0192-6233}, mesh = {Animals ; Asbestos/toxicity ; Free Radicals ; Humans ; Iron/*metabolism ; Lung/metabolism ; Lung Diseases/*etiology ; Metals/metabolism ; Mineral Fibers/*toxicity ; Oxidative Stress ; Protein Binding ; }, abstract = {Exposures to fibers and particles can be associated with several different lung injuries including bronchitis, bronchiolitis, pneumonitis, pleuritis, pulmonary alveolar proteinosis, pneumoconiosis, mesotheliomas, and lung cancers. The mechanism of biological effect exerted by fibers and particles has not been exactly defined. Exposures to all fibers and particles introduce a solid-liquid interface into the lower respiratory tract. These surfaces all have some concentration of oxygen-containing functional groups that demonstrate a capacity to coordinate iron. Radical generation is catalyzed by this metal resulting in a cascade of cell signaling, transcription factor activation, and mediator release. We propose that the ferruginous body (i.e., a fiber or particle with a coating of both protein and iron) provides direct evidence of a participation of iron in the biological effect of both fibers and particles. It is recommended that an identification of ferruginous bodies in the lung be regarded as support for a metal-catalyzed oxidative stress in the mechanism of cell and tissue injury.}, } @article {pmid15510989, year = {2004}, author = {Huncharek, M and Bseiso, A and Hutchins, L and Warner, J}, title = {Presentation of malignant pleural mesothelioma with symptomatic brain metastasis: report of a case.}, journal = {Tumori}, volume = {90}, number = {4}, pages = {424-427}, doi = {10.1177/030089160409000413}, pmid = {15510989}, issn = {0300-8916}, mesh = {Aged ; Brain Neoplasms/*diagnosis/diagnostic imaging/*secondary ; Diagnosis, Differential ; Humans ; Male ; Mesothelioma/*diagnosis/diagnostic imaging/secondary ; Pleural Neoplasms/*diagnosis/diagnostic imaging/pathology ; Tomography, X-Ray Computed ; }, abstract = {Central nervous system metastases from diffuse malignant pleural mesothelioma are rare. Here we describe a patient without known asbestos exposure who presented with chest pain, increasing shortness of breath and persistent headache. Evaluation found biphasic malignant mesothelioma of the right hemithorax and a single brain metastasis confirmed by computed tomography. This represents only the second case of a patient with pleural mesothelioma presenting with symptomatic central nervous system metastases.}, } @article {pmid15510812, year = {2004}, author = {Yamamoto, S and Shirakusa, T}, title = {[Extrapleural pneumonectomy for malignant pleural mesothelioma and primary lung cancer].}, journal = {Kyobu geka. The Japanese journal of thoracic surgery}, volume = {57}, number = {11}, pages = {1005-1010}, pmid = {15510812}, issn = {0021-5252}, mesh = {Adult ; Humans ; Lung Neoplasms/*surgery ; Male ; Mesothelioma/*surgery ; Middle Aged ; Pleural Neoplasms/*surgery ; Pneumonectomy/*methods ; }, abstract = {The extrapleural pneumonectomy for 6 patients with malignant pleural mesothelioma and 2 patients with primary lung cancer have been performed in our unit in those 10 years. Range of the age was 48-57 year-old. All of them were male and have been in occupational asbestos exposure. The mean survival time after extrapleural pneumonectomy was 620 days. In those, we experienced a case of malignant mesothelioma with excellent reduction by induction therapy of cisplatin+docetaxel hydrate, who underwent the extrapleural pneumonectomy continuously. We mentioned more over about the role of extrapleural pneumonectomy for primary lung cancer with pleural dissemination, and intrapleural perfusion hyperthermo-therapy for malignant mesothelioma.}, } @article {pmid15500660, year = {2004}, author = {Thomas, DH and Attanoos, RL and Gibbs, AR}, title = {Coexistent atypical adenomatous hyperplasia, primary lung adenocarcinoma and pleural mesothelioma in an asbestos-exposed subject.}, journal = {Histopathology}, volume = {45}, number = {5}, pages = {540-542}, doi = {10.1111/j.1365-2559.2004.01939.x}, pmid = {15500660}, issn = {0309-0167}, mesh = {Adenocarcinoma/chemically induced/*pathology ; Asbestos/*adverse effects ; Humans ; Hyperplasia/chemically induced/*pathology ; Lung/*pathology ; Lung Neoplasms/chemically induced/*pathology ; Male ; Mesothelioma/chemically induced/*pathology ; Middle Aged ; Pleural Neoplasms/chemically induced/*pathology ; }, } @article {pmid15496233, year = {2004}, author = {Webb, CP and Pass, HI}, title = {Translation research: from accurate diagnosis to appropriate treatment.}, journal = {Journal of translational medicine}, volume = {2}, number = {1}, pages = {35}, pmid = {15496233}, issn = {1479-5876}, abstract = {This review article focuses on the various aspects of translational research, where research on human subjects can ultimately enhance the diagnosis and treatment of future patients. While we will use specific examples relating to the asbestos related cancer mesothelioma, it should be stressed that the general approach outlined throughout this review is readily applicable to other diseases with an underlying molecular basis. Through the integration of molecular-based technologies, systematic tissue procurement and medical informatics, we now have the ability to identify clinically applicable "genotype"-"phenotype" associations across cohorts of patients that can rapidly be translated into useful diagnostic and treatment strategies. This review will touch on the various steps in the translational pipeline, and highlight some of the most essential elements as well as possible roadblocks that can impact success of the program. Critical issues with regard to Institutional Review Board (IRB) and Health Insurance Portability and Accountability Act (HIPAA) compliance, data standardization, sample procurement, quality control (QC), quality assurance (QA), data analysis, preclinical models and clinical trials are addressed. The various facets of the translational pipeline have been incorporated into a fully integrated computational system, appropriately named Dx2Tx. This system readily allows for the identification of new diagnostic tests, the discovery of biomarkers and drugable targets, and prediction of optimal treatments based upon the underlying molecular basis of the disease.}, } @article {pmid15490967, year = {2004}, author = {Tweedale, G and McCulloch, J}, title = {Chrysophiles versus chrysophobes: the white asbestos controversy, 1950s-2004.}, journal = {Isis; an international review devoted to the history of science and its cultural influences}, volume = {95}, number = {2}, pages = {239-259}, doi = {10.1086/426196}, pmid = {15490967}, issn = {0021-1753}, mesh = {Asbestos/adverse effects/*history ; Asbestos, Amphibole/history ; Asbestos, Crocidolite/history ; Asbestos, Serpentine/history ; Asbestosis/diagnosis/*history ; Global Health ; History, 20th Century ; Humans ; Lung Neoplasms/chemically induced/*history ; Mesothelioma/chemically induced/*history ; Risk Factors ; }, abstract = {In the first half of the twentieth century, asbestos was a controversial mineral because of its association with asbestosis and asbestos-related lung cancer. It has proved no less so since the 1960s, when another asbestos cancer, mesothelioma, was identified. Mesothelioma appeared to be more strongly linked with blue asbestos (crocidolite) than with the other asbestos varieties, brown (amosite) and white (chrysotile). This finding triggered a fierce debate between "chrysophiles" (those who declared chrysotile innocuous) and "chrysophobes" (those who believed it was a mortal hazard). This essay attempts the first history of the chrysotile controversy, which shows that a scientific consensus on the safety of white asbestos was very slow to emerge. This was only partly due to the complexities of scientific research. Political, economic, and social factors have militated against a speedy resolution of the debate, facilitating the continued production and use of asbestos in the developing world.}, } @article {pmid15486399, year = {2004}, author = {Pistolesi, M and Rusthoven, J}, title = {Malignant pleural mesothelioma: update, current management, and newer therapeutic strategies.}, journal = {Chest}, volume = {126}, number = {4}, pages = {1318-1329}, doi = {10.1378/chest.126.4.1318}, pmid = {15486399}, issn = {0012-3692}, mesh = {Antimetabolites, Antineoplastic/pharmacology/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Glutamates/pharmacology/therapeutic use ; Guanine/*analogs & derivatives/pharmacology/therapeutic use ; Humans ; Immunohistochemistry ; Mesothelioma/diagnosis/epidemiology/pathology/*therapy ; Neoplasm Staging ; Palliative Care ; Pemetrexed ; Pleural Neoplasms/diagnosis/epidemiology/pathology/*therapy ; Pleurodesis ; Prognosis ; Thoracoscopy ; }, abstract = {The diagnosis and management of malignant pleural mesothelioma are major challenges that often frustrate both patient and clinician alike. Occupational asbestos exposure to crocidolite or amosite forms of the fiber is the most important known risk factor in North America and Western Europe. Other mineral fibers such as erionite, a naturally occurring fibrous zeolite crystal, are associated with mesothelioma in volcanic tuffs of the Cappadocia region of central Anatolia in Turkey. In addition, other possible factors such as the presence of simian virus 40 and genetic susceptibility have been associated recently with the development of mesothelioma in animal models. These latter findings are increasing our understanding of this disease. In addition, the discovery of elevated levels of various markers such as folic acid receptor alpha, cyclooxygenase 2, and multidrug resistance proteins 1 and 2 in mesothelioma tissue have opened up new areas of potential diagnostic and therapeutic importance. However, traditional treatment modalities--surgery, radiotherapy, and chemotherapy--have evolved slowly, and few gains in therapeutic efficacy have occurred. Recently, however, continuing research efforts have led to novel treatment strategies that are changing the way clinicians view a disease that has traditionally been managed with almost universal therapeutic nihilism. This review explores our current knowledge of this disease and presents current and novel therapeutic strategies.}, } @article {pmid15480427, year = {2004}, author = {Kopnin, PB and Kravchenko, IV and Furalyov, VA and Pylev, LN and Kopnin, BP}, title = {Cell type-specific effects of asbestos on intracellular ROS levels, DNA oxidation and G1 cell cycle checkpoint.}, journal = {Oncogene}, volume = {23}, number = {54}, pages = {8834-8840}, doi = {10.1038/sj.onc.1208108}, pmid = {15480427}, issn = {0950-9232}, mesh = {Animals ; Asbestos, Serpentine/*toxicity ; Blotting, Northern ; Blotting, Western ; Cell Division/drug effects ; Cells, Cultured ; DNA/*drug effects/metabolism ; *G1 Phase ; Oxidation-Reduction ; Pleura/cytology/drug effects ; Rats ; Rats, Wistar ; *Reactive Oxygen Species ; }, abstract = {Exposure to asbestos fibers increases the risk of development of mesotheliomas and lung carcinomas, but not fibrosarcomas. We present data suggesting that resistance of fibroblasts to asbestos-induced carcinogenesis is likely to be connected with their lower ability to generate reactive oxygen species (ROS) in response to asbestos exposure and stricter control of proliferation of cells bearing asbestos/ROS-induced injuries. In fact, chrysotile (Mg6Si4O10(OH)8) asbestos exposure (5-10 microg/cm2) increased intracellular ROS and 8-oxo-guanine contents in rat pleural mesothelial cells, but not in lung fibroblasts. Simultaneously, moderate dosages of chrysotile and other agents increasing ROS levels (hydrogen peroxide, H2O2 and ethyl-methanesulfonate, EMS) inhibited cell cycle progression, in particular G1-to-S transition, in fibroblasts, but not in mesothelial cells. The arrested fibroblasts underwent cell death, while the majority of chrysotile-treated mesothelial cells survived. The differences in cell cycle response to asbestos/ROS-induced injuries correlated with distinct activity of p53-p21Cip1/Waf1 pathway in the two cell types. Chrysotile, H2O2 and EMS caused p53 upregulation in both cell types, but mesothelial cells, unlike fibroblasts, showed no accumulation of p21Cip1/Waf1. Of note, treatment with doxorubicin caused similar p53-dependent p21Cip1/Waf1 upregulation and cell cycle arrest in both cell types. This suggests differential response of fibroblasts and mesothelial cells specifically to asbestos/ROS exposure rather than to all DNA-damaging insults.}, } @article {pmid15469478, year = {2004}, author = {Attanoos, RL and Gibbs, AR}, title = {The pathology associated with therapeutic procedures in malignant mesothelioma.}, journal = {Histopathology}, volume = {45}, number = {4}, pages = {393-397}, doi = {10.1111/j.1365-2559.2004.01928.x}, pmid = {15469478}, issn = {0309-0167}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Diagnosis, Differential ; Humans ; Iatrogenic Disease ; Mesothelioma/pathology/*therapy ; Pleural Neoplasms/pathology/*therapy ; *Pleurodesis ; *Radiotherapy ; Talc/therapeutic use ; Treatment Outcome ; }, abstract = {AIMS: To describe iatrogenic pathological lesions in malignant pleural mesothelioma.

METHODS AND RESULTS: All cases of malignant pleural mesothelioma confirmed by antemortem pleural biopsy and undergoing post mortem examination over a 7-year period (1995-2001) formed the study group. This comprised 48 malignant pleural mesotheliomas [epithelioid (n = 21), biphasic (n = 14) and sarcomatoid (n = 13)]. Twenty-eight of 48 (58%) had received chemical (talc) pleurodesis, 30/48 (63%) palliative localized radiotherapy, 6/48 (13%) chemotherapy, and 14/48 (30%) surgery [12/48 (26%) pleural decortication and 2/48 (4%) pleuropneumonectomy].

CONCLUSIONS: Talc pleurodesis induces a marked pseudosarcomatous fibroblastic proliferation which may impart a biphasic pattern to the neoplasm. In more chronic cases, paucicellular fibrosis with a foreign body giant cell reaction is noted. The talc is polarizable and deposited in linear fashion within the tumour. In 2/28 (7%) pleurodesis cases platyform ferruginous bodies were seen in the peripheral alveolated lung parenchyma and these mimicked asbestos bodies. An awareness of this is important to prevent false attribution to asbestos. Talc could be identified by transmission electron microscopic mineral analysis in 5/15 (33%) cases examined. Tumour nodules developing subjacent to iatrogenic wound sites were noted in 8/48 (17%) cases. In 6/8 (75%) of these cases, comparative assessment of the locally irradiated subcutaneous chest wall tumour, with background pleural mesothelioma, showed no morphological difference in architectural tumour growth pattern, extent of necrosis, cytological or nuclear pleomorphism, mitotic activity or tumour immunophenotype. In 2/8 (25%) cases the locally irradiated tumour showed prominent bizarre multinucleated tumour giant cells and intense mixed inflammation, a feature not seen in the background (non-irradiated) tumour. All six malignant pleural mesotheliomas receiving chemotherapy appeared refractory to treatment in that chemotherapy did not appear to have any significant effect on the tumour morphology, cytonuclear pleomorphism, mitotic activity, extent of necrosis or immunophenotype. In the 12 decortication specimens and two pleuropneumonectomy resections, post mortem examination identified evidence of residual malignant mesothelioma of similar morphological subtype and immunophenotype to the resected tumour.}, } @article {pmid15468903, year = {2004}, author = {Burdorf, A and Dahhan, M and Swuste, PH}, title = {[Pleural mesothelioma in women is associated with environmental exposure to asbestos].}, journal = {Nederlands tijdschrift voor geneeskunde}, volume = {148}, number = {35}, pages = {1727-1731}, pmid = {15468903}, issn = {0028-2162}, mesh = {Adult ; Aged ; Aged, 80 and over ; Air Pollutants/*adverse effects ; Asbestos/*adverse effects ; Cause of Death ; Data Collection ; Environmental Exposure/*adverse effects ; Environmental Monitoring ; Epidemiological Monitoring ; Female ; Humans ; Mesothelioma/epidemiology/*etiology/mortality ; Middle Aged ; Netherlands/epidemiology ; Occupational Exposure/adverse effects ; Pleural Neoplasms/epidemiology/*etiology/mortality ; Residence Characteristics ; }, abstract = {OBJECTIVE: To determine whether local environmental exposure to asbestos in the community of Hof van Twente, The Netherlands (which houses a large asbestos cement facility and has a serious environmental asbestos pollution problem), is accompanied by an increased mortality due to pleural mesothelioma among women.

DESIGN: A descriptive, ecologic-epidemiological study.

METHOD: Twenty-nine women with a verified diagnosis of pleural mesothelioma were selected from 810 requests for compensation submitted to a specialised lawyers' office in the period 1990-2002. Information on asbestos exposure from occupational, household, environmental or unknown sources was obtained. The place of residence was compared to information on sources of asbestos in the immediate environment derived from the settlement 'Asbestos removal in the environment'. The expected number of cases of pleural mesothelioma among women was estimated on the basis of the observed mortality in The Netherlands in the period 1996-2002. A standardised mortality ratio (SMR) was calculated as the ratio of observed cases divided by the number of expected cases of pleural mesothelioma x 100.

RESULTS: In total, 5 cases of pleural mesothelioma were identified among women without occupational or household exposure to asbestos. The age at diagnosis varied from 38 to 81 years. Each case was exposed to asbestos in the direct vicinity of the residence through walking and cycling over local roads metalled with asbestos cement scrap material. The expected number of cases of mortality due to pleural mesothelioma in the town of Hof van Twente for the period 1996-2002 was about 0.46. The SMR was 1090 (95% CI: 465-2551), indicating a 10-fold increase in risk.

CONCLUSION: The increased mortality of pleural mesothelioma was most probably due to environmental exposure to asbestos. This finding agrees with comparable studies in other countries.}, } @article {pmid15466505, year = {2004}, author = {Lange, JH}, title = {Re: "Mesothelioma trends in the United States: an update based on surveillance, epidemiology, and end results program data for 1973 through 2003".}, journal = {American journal of epidemiology}, volume = {160}, number = {8}, pages = {823}, doi = {10.1093/aje/kwh279}, pmid = {15466505}, issn = {0002-9262}, mesh = {Asbestos/*poisoning ; Environmental Exposure/*adverse effects ; Humans ; Mesothelioma/epidemiology/*etiology ; Polyomavirus Infections/complications ; SEER Program ; Simian virus 40 ; Tumor Virus Infections/complications ; United States ; }, } @article {pmid15459048, year = {2004}, author = {Burton, B}, title = {Criminal investigation follows report on asbestos compensation fund.}, journal = {BMJ (Clinical research ed.)}, volume = {329}, number = {7469}, pages = {762}, doi = {10.1136/bmj.329.7469.762-b}, pmid = {15459048}, issn = {1756-1833}, mesh = {Asbestos/*toxicity ; Compensation and Redress/*legislation & jurisprudence ; *Crime ; Humans ; Mesothelioma/*chemically induced ; New South Wales ; }, } @article {pmid15455351, year = {2005}, author = {Triozzi, PL and Aldrich, W and Allen, KO and Lima, J and Shaw, DR and Strong, TV}, title = {Antitumor activity of the intratumoral injection of fowlpox vectors expressing a triad of costimulatory molecules and granulocyte/macrophage colony stimulating factor in mesothelioma.}, journal = {International journal of cancer}, volume = {113}, number = {3}, pages = {406-414}, doi = {10.1002/ijc.20574}, pmid = {15455351}, issn = {0020-7136}, support = {5P30CA13148/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Asbestos/toxicity ; Birds ; Cancer Vaccines ; Carcinogens/toxicity ; Cell Proliferation/drug effects ; DNA, Recombinant ; Female ; Fowlpox/*genetics/immunology ; Genetic Vectors/*therapeutic use ; Granulocyte-Macrophage Colony-Stimulating Factor/genetics/*immunology ; Immunoglobulin G/blood ; Mesothelioma/chemically induced/immunology/*therapy ; Mice ; Mice, Inbred BALB C ; Mice, Inbred CBA ; Survival Rate ; Vaccination ; Vaccines, Synthetic/genetics/*therapeutic use ; }, abstract = {Deficiency in costimulatory molecule expression has been implicated in the ability of tumors to escape immune effectors. The activity of the intratumoral administration of recombinant fowlpox vectors expressing a triad of costimulatory molecules (rF-TRICOM) was evaluated in the asbestos-induced AB12 and AC29 mouse models of mesothelioma. Mesothelioma cell infected with rF-TRICOM expressed high levels of the costimulatory molecules. Prolongation of survival was observed in mice receiving rF-TRICOM in AB12 and AC29 intraperitoneal models. Complete tumor regressions were observed in mice receiving intratumoral rF-TRICOM in the AB12 subcutaneous tumor model. Tumor regressions were associated with the development of serum IgG reactivities to mesothelioma-associated determinants and specific systemic cytolytic activity, and responding mice were capable of rejecting tumors upon re-challenge. Antitumor activity was also observed in mice with established AB12 tumor vaccinated with irradiated rF-TRICOM-infected AB12 cells. The antitumor activity of intratumoral rF-TRICOM was superior to that of the intratumoral injection of a fowlpox vector expressing granulocyte-macrophage colony stimulating factor (rF-GM-CSF). AB12 and AC29 tumors were found to produce GM-CSF and to have substantial macrophage infiltration. Production of GM-CSF decreased in vivo in tumors injected with rF-TRICOM. rF-TRICOM and wild-type fowlpox inhibited the growth of AB12 and AC29 cells in vitro; less inhibition was observed with rF-GM-CSF. These results indicate that the intratumoral injection of rF-TRICOM has significant activity in mouse models of mesothelioma and can elicit a systemic antitumor immune response. The results also suggest potential limitations to the intratumoral administration of cytokines, such as GM-CSF, in mesothelioma.}, } @article {pmid15451223, year = {2004}, author = {López-Ríos, F and Illei, PB and Rusch, V and Ladanyi, M}, title = {Evidence against a role for SV40 infection in human mesotheliomas and high risk of false-positive PCR results owing to presence of SV40 sequences in common laboratory plasmids.}, journal = {Lancet (London, England)}, volume = {364}, number = {9440}, pages = {1157-1166}, doi = {10.1016/S0140-6736(04)17102-X}, pmid = {15451223}, issn = {1474-547X}, mesh = {Adult ; Aged ; Antigens, Viral, Tumor/analysis/genetics ; Cell Line, Tumor/virology ; Clinical Laboratory Techniques ; DNA, Viral/genetics ; False Positive Reactions ; Humans ; Immunohistochemistry ; Mesothelioma/*virology ; Middle Aged ; Plasmids/genetics ; Polymerase Chain Reaction ; Polyomavirus Infections/complications/*diagnosis ; Risk ; Sequence Analysis, DNA ; Simian virus 40/genetics/immunology/*isolation & purification ; Tumor Virus Infections/complications/*diagnosis ; }, abstract = {BACKGROUND: PCR-based evidence of infection by simian virus 40 (SV40) has been reported in varying proportions of pleural mesotheliomas and other tumours, but data are conflicting and reproducibility limited. During a study of SV40 in relation to homozygous deletion of CDKN2A in mesotheliomas, we became concerned by inconsistent results and therefore used several independent techniques to investigate SV40 in these tumours.

METHODS: High-quality DNA and RNA were extracted from 71 frozen mesothelioma samples. DNA PCR was done with four sets of primers for the SV40 T-antigen gene. RNA transcripts were examined by RT-PCR.

FINDINGS: The first two primer sets for DNA PCR gave positive results in proportions similar to those reported in positive studies (56-62%) but there were unusual reproducibility difficulties. These primers were in a region of the T-antigen gene (nucleotides 4100-4713) that is present in many common laboratory plasmids. In assays with PCR primers not included within that region, only four cases (6%) showed products but these were too faint to suggest clonal infection. Further PCR assays confirmed that the SV40 sequences in the tumour samples had a deletion found only in plasmids, not in native functional SV40. Review of previous studies showed a similar pattern of discrepancies between SV40 T-antigen DNA PCR results obtained with primers within and beyond the region 4100-4713. All 71 mesotheliomas were negative for T-antigen transcripts by RT-PCR, and lacked T-antigen-positive tumour cells by immunohistochemistry.

INTERPRETATION: Our data based on three independent experimental approaches do not support a significant role for SV40 in human mesotheliomas. The risk of false-positive results due to contamination by common laboratory plasmids containing SV40 sequences has been underestimated. Studies of SV40 based on PCR methods require careful primer design to reduce this risk.

RELEVANCE TO PRACTICE: This paper presents several lines of evidence against the proposed link between SV40 infection and human mesotheliomas. Studies reporting a high prevalence of SV40 DNA in human tumours have been based on molecular assays prone to false-positive results. Because SV40 appears unlikely to have a major role, if any, in human mesotheliomas, clinicians should continue to consider asbestos exposure as the most likely and most thoroughly established aetiological factor in individuals with this cancer.}, } @article {pmid15386418, year = {2005}, author = {Burdorf, A and Järvholm, B and Englund, A}, title = {Explaining differences in incidence rates of pleural mesothelioma between Sweden and the Netherlands.}, journal = {International journal of cancer}, volume = {113}, number = {2}, pages = {298-301}, doi = {10.1002/ijc.20552}, pmid = {15386418}, issn = {0020-7136}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Asbestos/*poisoning ; Female ; Humans ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Netherlands/epidemiology ; *Occupational Exposure ; Pleural Neoplasms/*epidemiology ; Registries/*statistics & numerical data ; Sweden/epidemiology ; }, abstract = {In recent years in several countries a deceleration or leveling off of pleural mesothelioma rates has been observed. The impact of asbestos used was analysed by comparing a country with a relative modest incidence rate of mesothelioma (Sweden) and an early response to asbestos use with a country with one of the highest incidence rates of mesothelioma in Western Europe (The Netherlands). In Sweden the Cancer Register provided information on the annual incidence of pleural mesothelioma, whereas in The Netherlands mortality data were provided by Statistics Netherlands for the period 1969-2001. In The Netherlands among men the incidence rate was consistently higher (1.5-2 times) than in Sweden, whereas among women similar rates were observed. Assuming that none of the female cases was caused by occupational exposure to asbestos, minimum estimates of the etiologic fraction for occupational exposure to asbestos in men would be 82% in Sweden and 92% in The Netherlands. Possible explanations for the consistently higher incidence rates in the Netherlands than in Sweden include differences in exposure levels, the proportion of exposed subjects in the workforce and types of asbestos fibres used. Measures to decrease the exposure to asbestos seem to have decreased the risk of pleural mesothelioma in both countries among age groups below 60 years. This effect will result in a leveling off of the increase in pleural mesothelioma in both countries in the next decade.}, } @article {pmid15366334, year = {2004}, author = {Janssen, JP}, title = {Is thoracoscopic talc pleurodesis really safe?.}, journal = {Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace}, volume = {61}, number = {1}, pages = {35-38}, pmid = {15366334}, issn = {1122-0643}, mesh = {Cardiovascular Diseases/etiology ; Empyema/etiology ; Humans ; Pleurodesis/*adverse effects ; Respiratory Distress Syndrome/etiology ; Respiratory Insufficiency/etiology ; Talc/*poisoning ; Thoracoscopy/adverse effects/methods ; }, abstract = {Talc is a mineral defined as hydrated magnesium silicate in its pure form. It is mined in open pits throughout the world. For induction of chemical pleurodesis, talc has been shown to be superior to all other products. The safety of the use of talc for pleurodesis is subject to discussion in the literature. In early days, there was concern about asbestos contamination of talc, which could cause mesothelioma in patients who had undergone talc pleurodesis. The long-term safety of talc was proven in several studies, and today talc for pharmaceutical use is asbestos-free. Today the discussion is concentrated on the early complications of talc; Acute respiratory failure, sometimes with fatal outcome, has been attributed to the intrapleural use of talc particles. In recent animal studies, a relation was demonstrated between the size of talc particles and pulmonary injury as well as dissemination to other organs. Pulmonary injury and dissemination to other organs are related to a talc particle size of less than 10 micro. With certain precautions, talc can be used safely for pleurodesis; Simultaneous bilateral procedures, concomitant pulmonary biopsies and use of more than 5 grams of talc should be avoided. As long as the hypothesis about the influence of particle size on complications has not been confirmed by studies in humans, the use of talc with a large mean particle diameter is to be preferred.}, } @article {pmid15361226, year = {2004}, author = {Lange, JH and Hoskins, JA}, title = {Asbestos in drinking water does not cause mesothelioma.}, journal = {International journal of gynecological cancer : official journal of the International Gynecological Cancer Society}, volume = {14}, number = {5}, pages = {1048-9; author reply 1046-7}, doi = {10.1111/j.1048-891X.2004.014551.x}, pmid = {15361226}, issn = {1048-891X}, mesh = {Aged ; Asbestos/*adverse effects ; Female ; Food Contamination ; Humans ; Mesothelioma/*chemically induced ; Peritoneal Neoplasms/*chemically induced ; Reproducibility of Results ; Water Pollutants, Chemical/*adverse effects ; Water Supply ; }, } @article {pmid15358845, year = {2004}, author = {Kinoulty, M}, title = {Monitor. Mesothelioma deaths in Great Britain.}, journal = {Occupational medicine (Oxford, England)}, volume = {54}, number = {6}, pages = {436}, doi = {10.1093/occmed/kqh129}, pmid = {15358845}, issn = {0962-7480}, mesh = {Asbestos/toxicity ; *Disease Outbreaks ; Humans ; Lung Neoplasms/*mortality/surgery ; Male ; Mesothelioma/*mortality/surgery ; Occupational Diseases/*mortality/surgery ; United Kingdom/epidemiology ; }, } @article {pmid15343491, year = {2004}, author = {Dhom, G}, title = {[The history of bronchial carcinoma].}, journal = {Pneumologie (Stuttgart, Germany)}, volume = {58}, number = {9}, pages = {680-685}, doi = {10.1055/s-2004-818417}, pmid = {15343491}, issn = {0934-8387}, mesh = {Asbestos/history ; Carcinoma, Bronchogenic/*history/pathology ; History, 19th Century ; History, 20th Century ; Humans ; }, abstract = {Up to the mid 19 (th) century primary bronchial carcinoma was unknown. Primary tumours and metastases of malignant lung tumours were often not distinguished one from the other. Only in 1871, Theodor Langhans from Marburg reported the first certain observation of bronchial carcinoma. Definite information on the increasing frequency of lung and bronchial carcinomas at the beginning of the 20 (th) century was only obtained by autopsy statistics. The Cancer Registry of the Saarland showed that the incidence of lung cancer has not increased since 1970 in men, but has tripled in women. Already in 1923, Theodor Fahr from Hamburg referred to the danger of smoking. In Germany the so-called Schneeberg's lung cancer plays an important role among occupational lung cancer diseases. Only after Germany's reunification the drama of the uranium miners of the former so-called Wismut AG became fully known. Regarding occupational diseases, asbestos-related bronchial carcinomas and mesotheliomas are at the top of the causes of death today.}, } @article {pmid15343490, year = {2004}, author = {Müller, KM}, title = {[Pleuromesothelioma -- psychology and pathogenesis].}, journal = {Pneumologie (Stuttgart, Germany)}, volume = {58}, number = {9}, pages = {670-679}, doi = {10.1055/s-2004-818505}, pmid = {15343490}, issn = {0934-8387}, mesh = {Humans ; Lymphatic Metastasis ; Mesothelioma/*etiology/genetics/pathology/*psychology ; Pleural Neoplasms/*etiology/genetics/pathology/*psychology ; }, abstract = {Investigations into the anatomical pathology are of crucial importance for the diagnosis and therapy of pleural tumours. The main objective is to differentiate reactive hyperplastic proliferations of the mesothelium from already manifest primary or secondary malignant pleural tumours. Given the absence of distinct morphological features displayed by pleural mesotheliomas, specific additional immunohistochemical and cytometric tests can provide valuable clues for the differential diagnosis of primary and secondary pleural neoplasms. Confirmation of the diagnosis during the initial stages of tumour development i. e. mesothelioma in-situ and early mesothelioma necessitates invasive diagnostic procedure as early as possible. This holds particularly true if surgery is aimed at cure. However, in order to firmly establish the diagnosis considering the afore mentioned problems, the tissue specimens to be examined by a pathologist must be of adequate size. 90 % of all pleural mesotheliomas are asbestos associated due to occupational exposure. Therefore, all cases of a suspected pleural mesothelioma must be reported to the appropriate professional association as a potential occupational disease. The Bochum based German Mesothelioma Registry, which is supported by the head office of the German Professional Associations, conducts research and acts as an advisory institution in difficult cases, where problems concerning the classification of tumours by their anatomical pathology arise.}, } @article {pmid15339060, year = {2004}, author = {Kindler, HL}, title = {The emerging role of pemetrexed for the treatment of malignant mesothelioma.}, journal = {Oncology (Williston Park, N.Y.)}, volume = {18}, number = {8 Suppl 5}, pages = {49-53}, pmid = {15339060}, issn = {0890-9091}, mesh = {Antimetabolites, Antineoplastic/*therapeutic use ; Clinical Trials as Topic ; Glutamates/*therapeutic use ; Guanine/*analogs & derivatives/*therapeutic use ; Humans ; Lung Neoplasms/*drug therapy ; Mesothelioma/*drug therapy ; Pemetrexed ; Thymidylate Synthase/antagonists & inhibitors ; }, abstract = {Malignant mesothelioma is a devastating disease with an onset 20 to 60 years after exposure to asbestos. Although most cytotoxic agents have been evaluated for the treatment of mesothelioma, few single agents have consistently yielded response rates above 20%. Antimetabolites are the most active drugs against mesothelioma, and of these, the antifolate group is the most widely studied and effective. Pemetrexed (Alimta), a new antifolate, may be more active because of its different mechanism of action. Several clinical trials have evaluated pemetrexed alone and in combination with a platinum agent for patients with malignant mesothelioma. A pivotal phase III trial has demonstrated that combination chemotherapy with pemetrexed and cisplatin improves survival, response rate, pulmonary function, and quality of life compared with single-agent cisplatin. Additional trials are evaluating pemetrexed in the neoadjuvant setting and in combination with other cytotoxic and targeted agents.}, } @article {pmid15338944, year = {2004}, author = {Gallacher, R}, title = {Understanding the impact of malignant mesothelioma.}, journal = {Nursing times}, volume = {100}, number = {30}, pages = {45}, pmid = {15338944}, issn = {0954-7762}, mesh = {Asbestos/adverse effects ; Humans ; *Mesothelioma/diagnosis/etiology/therapy ; *Pleural Neoplasms/diagnosis/etiology/therapy ; }, } @article {pmid15338355, year = {2004}, author = {Liu, YC and Kuo, YL and Yu, CP and Wu, HS and Yu, JC and Chen, CJ and Chan, DC and Yu, CY and Hsieh, CB and Chen, TW}, title = {Primary malignant mesothelioma of the greater omentum: report of a case.}, journal = {Surgery today}, volume = {34}, number = {9}, pages = {780-783}, doi = {10.1007/s00595-004-2809-2}, pmid = {15338355}, issn = {0941-1291}, mesh = {Female ; Humans ; Immunohistochemistry ; Laparotomy ; Mesothelioma/*pathology/*surgery ; Middle Aged ; Omentum/*pathology/*surgery ; Peritoneal Neoplasms/*pathology/*surgery ; Tomography, X-Ray Computed ; }, abstract = {We report a rare case of primary malignant mesothelioma of the greater omentum. To our knowledge, only one other such case has been described in the English literature. The patient was a 61-year-old Taiwanese woman without any history of exposure to asbestos, who presented with lower back pain. Abdominal sonography and computed tomography showed a 12 x 9 x 9-cm(3) mass occupying the lower abdomen. Laparotomy revealed a tumor in the greater omentum, invading the posterior wall of the uterus, without diffuse mesenteric thickening or multiple small nodules in the peritoneum. We performed en bloc resection of the mass, which involved omentectomy, hysterectomy, and bilateral salpingo-oophorectomy. Microscopically, the tumor cells were arranged in a tubulopapillary pattern lined by a single layer of uniform, cuboidal cells. A pattern of sclerotic stroma with irregular glandular elements was also recognized. Immunohistochemically, the tumor cells showed strong positivity for calretinin. The final pathologic diagnosis was malignant mesothelioma. The patient did not receive chemotherapy or radiotherapy, and has remained in good health without any evidence of recurrence for almost 3 years since her operation.}, } @article {pmid15330815, year = {2004}, author = {Lee, AH and Soomro, IN}, title = {Collision tumour of the pleura composed of small cell carcinoma and malignant mesothelioma.}, journal = {Histopathology}, volume = {45}, number = {3}, pages = {305-306}, doi = {10.1111/j.1365-2559.2004.01900.x}, pmid = {15330815}, issn = {0309-0167}, mesh = {Aged ; Aged, 80 and over ; Asbestos/poisoning ; Biomarkers ; Biomarkers, Tumor/analysis ; CD56 Antigen/analysis ; Calbindin 2 ; Carcinoembryonic Antigen/analysis ; Carcinoma, Small Cell/etiology/metabolism/*pathology ; Fatal Outcome ; Histocytochemistry ; Humans ; Keratin-5 ; Keratins/analysis ; Lung Neoplasms/etiology/metabolism/*pathology ; Male ; Mesothelioma/etiology/metabolism/*pathology ; Neoplasms, Multiple Primary/etiology/metabolism/*pathology ; Nuclear Proteins/analysis ; Occupational Exposure/adverse effects ; Pleural Neoplasms/etiology/metabolism/*pathology ; S100 Calcium Binding Protein G/analysis ; Thyroid Nuclear Factor 1 ; Transcription Factors/analysis ; Vimentin/analysis ; }, } @article {pmid15322513, year = {2004}, author = {Boffetta, P}, title = {Epidemiology of environmental and occupational cancer.}, journal = {Oncogene}, volume = {23}, number = {38}, pages = {6392-6403}, doi = {10.1038/sj.onc.1207715}, pmid = {15322513}, issn = {0950-9232}, mesh = {Air Pollution, Indoor ; Asbestos/adverse effects ; Environmental Exposure ; Environmental Pollution/*adverse effects ; Humans ; Neoplasms/*epidemiology/etiology ; Occupational Diseases/*epidemiology ; Smoke/adverse effects ; Tobacco Smoke Pollution ; }, abstract = {Environmental carcinogens, in a strict sense, include outdoor and indoor air pollutants, as well as soil and drinking water contaminants. An increased risk of mesothelioma has consistently been detected among individuals experiencing residential exposure to asbestos, while results for lung cancer are less consistent. Several good-quality studies have investigated lung cancer risk from outdoor air pollution based on measurement of specific agents. Their results tend to show an increased risk in the categories at highest exposure, with relative risks in the range 1.5. A causal association has been established between exposure to environmental tobacco smoke and lung cancer, with a relative risk in the order of 1.2. Radon is another carcinogen present in indoor air, with a relative risk in the order of 1.06 for exposure at 100 Bq/m3. In several Asian populations, an increased risk of lung cancer results among women from indoor pollution from cooking and heating. There is strong evidence of an increased risk of bladder, skin and lung cancers following consumption of water with high arsenic contamination; results for other drinking water contaminants, including chlorination by-products, are inconclusive. A total of 29 occupational agents are established human carcinogens, and another 30 agents are suspected carcinogens. In addition, at least 12 exposure circumstances entail exposure to carcinogens. Exposure is still widespread for many important occupational carcinogens, such as asbestos, coal tar, arsenic and silica, in particular in developing countries. Although estimates of the global burden of occupational and environmental cancer result in figures in the order of 2% and less than 1%, respectively, these cancers concentrate in subgroups of the population; furthermore, exposure is involuntary and can, to a large extent, be avoided.}, } @article {pmid15308938, year = {2004}, author = {Weber, MA and Bock, M and Plathow, C and Wasser, K and Fink, C and Zuna, I and Schmähl, A and Berger, I and Kauczor, HU and Schoenberg, SO}, title = {Asbestos-related pleural disease: value of dedicated magnetic resonance imaging techniques.}, journal = {Investigative radiology}, volume = {39}, number = {9}, pages = {554-564}, doi = {10.1097/01.rli.0000131888.39636.c5}, pmid = {15308938}, issn = {0020-9996}, mesh = {Aged ; Aged, 80 and over ; Asbestosis/*diagnosis/diagnostic imaging ; Female ; Humans ; *Magnetic Resonance Imaging/methods ; Male ; Mesothelioma/diagnosis/diagnostic imaging ; Middle Aged ; Observer Variation ; Pleura/diagnostic imaging/pathology ; Pleural Diseases/*diagnosis/diagnostic imaging ; Pleural Neoplasms/diagnosis/diagnostic imaging ; Sensitivity and Specificity ; Tomography, X-Ray Computed ; }, abstract = {OBJECTIVES: We sought to compare respiratory-gated high-spatial resolution magnetic resonance imaging (MRI) and radial MRI with ultra-short echo times with computed tomography (CT) in the diagnosis of asbestos-related pleural disease.

METHODS: Twenty-one patients with confirmed long-term asbestos exposure were examined with a CT and a 1.5-T MR unit. High-resolution respiratory-gated T2w turbo-spin-echo (TSE), breath-hold T1w TSE, and contrast-enhanced fat-suppressed breath-hold T1w TSE images with an inplane resolution of less than 1 mm were acquired. To visualize pleural plaques with a short T2* time, a pulse sequence with radial k-space-sampling was used (TE = 0.5 milliseconds) before and after administration of Gd-DTPA. CT and MR images were assessed by 4 readers for the number and calcification of plaques, extension of pleural fibrosis, extrapleural fat, detection of mesothelioma and its infiltration into adjacent tissues, and detection of pleural effusion. Observer agreement was studied with the use of kappa statistics.

RESULTS: The MRI protocol allowed for differentiation between normal pleura and pleura with plaques. Interobserver agreement was comparable for MRI and CT in detecting pleural plaques (median kappa = 0.72 for MRI and 0.73 for CT) and significantly higher with CT than with MRI for detection of plaque calcification (median kappa 0.86 for CT and 0.72 for MRI; P = 0.03). Median sensitivity of MRI was 88% for detection of plaque calcification compared with CT. For assessment of pleural thickening, pleural effusion, and extrapleural fat, interobserver agreement with MRI was significantly higher than with CT (median kappa 0.71 and 0.23 for pleural thickening, 0.87 and 0.62 for pleural effusion, and 0.7 and 0.56 for extrapleural fat, respectively; P < 0.05). For detection of mesothelioma, median kappa was 0.63 for MRI and 0.58 for CT.

CONCLUSION: High-resolution MR sequences and radial MRI achieve a comparable interobserver agreement in detecting pleural plaques and even a higher interobserver agreement in assessing pleural thickening, pleural effusion, and extrapleural fat when compared with CT.}, } @article {pmid15307130, year = {2004}, author = {Teta, MJ}, title = {RE: Asbestos in brakes: exposure and risk of disease.}, journal = {American journal of industrial medicine}, volume = {46}, number = {3}, pages = {312-4; author reply 315-8}, doi = {10.1002/ajim.20060}, pmid = {15307130}, issn = {0271-3586}, mesh = {Air Pollutants, Occupational/*toxicity ; Asbestos/*toxicity ; Asbestosis/*epidemiology/etiology ; *Automobiles ; Humans ; Manufactured Materials ; Mesothelioma/*epidemiology/etiology ; Occupational Exposure/*adverse effects ; Risk Assessment ; United States/epidemiology ; }, } @article {pmid15303546, year = {2004}, author = {Proietti, L and Migliore, M and Polosa, R and Comba, P and Circo, C and Di Maria, GU}, title = {[Malignant pleural mesothelioma in housewives in the province of Catania].}, journal = {Recenti progressi in medicina}, volume = {95}, number = {7-8}, pages = {365-368}, pmid = {15303546}, issn = {0034-1193}, mesh = {Aged ; Asbestos/adverse effects ; Carcinogens/adverse effects ; Female ; Genetic Predisposition to Disease ; Humans ; Italy/epidemiology ; Mesothelioma/epidemiology/*etiology ; Middle Aged ; Pleural Neoplasms/epidemiology/*etiology ; Polyomavirus Infections/complications ; Simian virus 40 ; Spouses/*statistics & numerical data ; Tumor Virus Infections/complications ; }, abstract = {Our study reports pleural malignant mesothelioma (PMM) in seven female patients. All patients were resident in Catania area (Sicily), the median age was 69.2 years and ranged from 59 to 81 years. They were housewife. Their anamnesis was negative for both direct and indirect previous exposure to asbestos; the partners of all patients were also not exposed to asbestos. The exposure to X-rays was also excluded for these patients. Different pathogenetic mechanisms for the appearance of PMM in these patients can be hypothesized, for example, SV40 infection and genetic susceptibility; a minimal domestic exposure to asbestos can be not excluded. Therefore, further studies in a more large number of subjects are necessary to determine whether one or all of these hypothetic pathogenetic mechanisms are more significant for the develop of PMM.}, } @article {pmid15302752, year = {2004}, author = {Manda-Stachouli, C and Dalavanga, Y and Daskalopoulos, G and Leontaridi, C and Vassiliou, M and Constantopoulos, SH}, title = {Decreasing prevalence of pleural calcifications among Metsovites with nonoccupational asbestos exposure.}, journal = {Chest}, volume = {126}, number = {2}, pages = {617-621}, doi = {10.1378/chest.126.2.617}, pmid = {15302752}, issn = {0012-3692}, mesh = {Adult ; Aged ; Asbestos/*poisoning ; Asbestos, Amphibole ; Calcinosis/*epidemiology ; Environmental Exposure ; Female ; Greece/epidemiology ; Humans ; Male ; Mesothelioma/epidemiology ; Middle Aged ; Pleural Diseases/*epidemiology ; Pleural Neoplasms/epidemiology ; Prevalence ; Retrospective Studies ; }, abstract = {STUDY OBJECTIVES: Twenty years ago, we reported on a very high prevalence of pleural calcifications (PCs) and malignant mesothelioma among inhabitants of Metsovo, in northwestern Greece. It was shown that both abnormalities were related to asbestos exposure from a whitewash containing tremolite. The fading use of this material has resulted in a decreased incidence of mesothelioma (one third of the original incidence). The aim of the present study was to examine whether PCs among Metsovites has followed a similar trend.

DESIGN: Retrospective study.

SETTINGS: University Hospital of Ioannina, a tertiary teaching hospital, "G. Hadjikosta" Hospital, a tertiary hospital in Ioannina, and Metsovo Health Center, a primary care center in the town of Metsovo.

PATIENTS: Chest roentgenograms of 307 Metsovites, obtained between from 1998 to 2002 were examined. The prevalence of PCs was compared to the one noted 20 years ago.

RESULTS: A significantly lower prevalence of calcifications was observed now among younger Metsovites (< 60 years of age). In both studies, there was an increasing rate of PC with age.

CONCLUSIONS: The findings of the present study strengthen the incrimination of the whitewash containing tremolite in the development of PCs in Metsovites. The withdrawal of its use in the area has resulted in a null prevalence of PCs in individuals < 40 years old.}, } @article {pmid15300814, year = {2004}, author = {Ascoli, V and Comba, P and Pasetto, R}, title = {Urban mesothelioma: is there an emerging risk of asbestos in place?.}, journal = {International journal of cancer}, volume = {111}, number = {6}, pages = {975-976}, doi = {10.1002/ijc.20346}, pmid = {15300814}, issn = {0020-7136}, mesh = {Asbestos/*adverse effects ; Cities ; *Environmental Exposure ; Epidemiologic Studies ; Female ; Humans ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology/*etiology ; *Occupational Exposure ; Prevalence ; Reproducibility of Results ; Risk Assessment ; Sex Factors ; Urban Population ; }, } @article {pmid15289586, year = {2004}, author = {Ross, MH and Murray, J}, title = {Occupational respiratory disease in mining.}, journal = {Occupational medicine (Oxford, England)}, volume = {54}, number = {5}, pages = {304-310}, doi = {10.1093/occmed/kqh073}, pmid = {15289586}, issn = {0962-7480}, mesh = {Adult ; Asbestosis/epidemiology/etiology ; Coal Mining ; Humans ; Lung Neoplasms/etiology ; Male ; Mesothelioma/etiology ; *Mining ; Occupational Diseases/epidemiology/*etiology ; Occupational Exposure/adverse effects ; Pneumoconiosis/epidemiology/etiology ; Prevalence ; Respiratory Tract Diseases/epidemiology/*etiology ; Risk Factors ; Silicosis/epidemiology/etiology ; Tuberculosis, Pulmonary/etiology ; }, abstract = {This review is based on research-based literature on occupational lung disease in the mining and related industries, focusing on conditions of public health importance arising from asbestos, coal and silica exposure. Both 'traditional' and 'new' concerns about occupational respiratory disease in miners are addressed, with the inclusion of practical evidence-based findings relevant to practitioners working in developed and developing countries. Mining is not a homogeneous industry since current miners work in formal and informal operations with numerous, and often multiple, air-borne exposures. A further occupational health challenge facing primary care practitioners are ex-miners presenting with disease only after long latency. The sequelae of silica exposure remain an occupational health priority, particularly for practitioners who serve populations with concomitant HIV and tuberculosis infection and even when exposure is apparently below the statutory occupational exposure level. Coal workers' pneumoconiosis, asbestos related diseases, lung cancer and other occupational respiratory diseases remain of considerable importance even after mining operations cease. While mining exposures contribute significantly to lung disease, smoking is a major factor in the development of lung cancer and chronic obstructive airways disease necessitating a comprehensive approach for prevention and control of mining-related occupational lung disease.}, } @article {pmid15288533, year = {2004}, author = {Schürkes, C and Brock, W and Abel, J and Unfried, K}, title = {Induction of 8-hydroxydeoxyguanosine by man made vitreous fibres and crocidolite asbestos administered intraperitoneally in rats.}, journal = {Mutation research}, volume = {553}, number = {1-2}, pages = {59-65}, doi = {10.1016/j.mrfmmm.2004.06.021}, pmid = {15288533}, issn = {0027-5107}, mesh = {8-Hydroxy-2'-Deoxyguanosine/analogs & derivatives ; Animals ; Asbestos, Crocidolite/administration & dosage/*toxicity ; DNA/chemistry/drug effects/*genetics ; Female ; Guanine/*analogs & derivatives/analysis/*metabolism ; Humans ; Injections, Intraperitoneal ; Macrophages, Peritoneal/drug effects/metabolism ; Mineral Fibers/*toxicity ; Rats ; Rats, Wistar ; Therapeutic Irrigation ; Tumor Necrosis Factor-alpha/metabolism ; }, abstract = {Inhaled fibres with certain physico-chemical properties are known to induce mesothelioma in humans. The induction of reactive oxygen (ROS) or nitrogen species (RNS) have been suggested as molecular mechanism of fibre induced carcinogenesis. In earlier studies we were able to demonstrate that crocidolite asbestos in vivo induces mutations in transgenic rats with a specific molecular spectrum that indicates the involvement of 8-hydroxydeoxyguanosine (8-OHdG) as pre-mutagenic adduct. 8-OHdG may be induced by primary (direct) and/or secondary (cellular mediated) mechanisms. Therefore, the induction of 8-OHdG as well as the inflammatory response of animals treated with fibre samples significantly differing in their physico-chemical characteristics was investigated. As appropriate system to study mesothelioma carcinogenesis, intraperitoneal injection in rats was used with samples of UICC crocidolite, crocidolite with reduced iron content, and a vitreous fibre (MMVF 11). Equal numbers of carcinogenic fibres from each sample revealed significant comparable increases in 8-OHdG induction. Parameters of inflammation (percentage of macrophages and TNF-alpha secretion) correlated significantly with the induction of 8-OHdG, 10 weeks after treatment.}, } @article {pmid15281606, year = {2004}, author = {Crosignani, P and Piffer, S}, title = {Respiratory tract cancers: lung and mesothelioma.}, journal = {Epidemiologia e prevenzione}, volume = {28}, number = {2 Suppl}, pages = {48-56}, pmid = {15281606}, issn = {1120-9763}, mesh = {Adult ; Aged ; Air Pollution/adverse effects ; Asbestos/adverse effects ; Databases, Factual ; Female ; Humans ; Incidence ; Italy/epidemiology ; Lung Neoplasms/*epidemiology/etiology ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Occupational Diseases/epidemiology ; Pleural Neoplasms/*epidemiology ; Registries/statistics & numerical data ; Retrospective Studies ; Sex Distribution ; Smoking/adverse effects/epidemiology ; Survival Rate ; Time Factors ; }, abstract = {The trend analysis of lung cancer in the database of the Italian Network of Cancer Registries (pool AIRT), showed, among males (52,267 incident cases and 46, 726 deaths included in the study) a statistically significant decrease of incidence and mortality in the period 1986-1997; incidence rates decreased by about 1.4%/year and mortality rates by about 1.6%/year. Among females, lung cancer trends are rather different from that of males, according to diverging trends in tobacco smoking exposures; in fact, both incidence (+1.2%/year) and mortality (+0.9%/year) are increasing. Incidence of mesothelioma (1594 cases), showed for the period 1986-1997, a statistically significant increase among both males and females; standardised rates increased, more than 4% every year. As regards to deaths due to pleural malignant cancers (1393 among males and 664 among females) their trend was stable in the analysed period.}, } @article {pmid15281385, year = {2004}, author = {Lemen, RA}, title = {Chrysotile asbestos as a cause of mesothelioma: application of the Hill causation model.}, journal = {International journal of occupational and environmental health}, volume = {10}, number = {2}, pages = {233-239}, doi = {10.1179/oeh.2004.10.2.233}, pmid = {15281385}, issn = {1077-3525}, mesh = {Asbestos, Serpentine/*adverse effects ; Causality ; Epidemiologic Methods ; Female ; Global Health ; Humans ; Male ; Mesothelioma/*epidemiology ; Mining/statistics & numerical data ; Models, Statistical ; Occupational Exposure/adverse effects/statistics & numerical data ; }, abstract = {Chrysotile comprises over 95% of the asbestos used today. Some have contended that the majority of asbestos-related diseases have resulted from exposures to the amphiboles. In fact, chrysotile is being touted as the form of asbestos which can be used safely. Causation is a controversial issue for the epidemiologist. How much proof is needed before causation can be established? This paper examines one proposed model for establishing causation as presented by Sir Austin Bradford Hill in 1965. Many policymakers have relied upon this model in forming public health policy as well as deciding litigation issues. Chrysotile asbestos meets Hill's nine proposed criteria, establishing chrysotile asbestos as a cause of mesothelioma.}, } @article {pmid15281382, year = {2004}, author = {Kjellstrom, TE}, title = {The epidemic of asbestos-related diseases in New Zealand.}, journal = {International journal of occupational and environmental health}, volume = {10}, number = {2}, pages = {212-219}, doi = {10.1179/oeh.2004.10.2.212}, pmid = {15281382}, issn = {1077-3525}, mesh = {Asbestosis/economics/*epidemiology/prevention & control ; Comorbidity ; Disease Outbreaks/economics/prevention & control/*statistics & numerical data ; Health Policy/legislation & jurisprudence ; Humans ; Mesothelioma/epidemiology ; New Zealand ; Occupational Exposure/economics/prevention & control/statistics & numerical data ; Risk Assessment ; Workers' Compensation/trends ; }, abstract = {New Zealand is a small country with a big asbestos disease problem. The lack of action on warnings in the 1960s and 1970s has led to epidemics of mesothelioma and asbestosis, which can be clearly documented via the death and cancer registers. In addition, an uncertain number of lung cancers due to asbestos exposure has occurred. The epidemic started in the 1980s, and will eventually have cost the lives of at least 2000 to 3000 workers. Prevention against ongoing exposures from asbestos installed in buildings is essential, and another key issue for New Zealand is to ensure that fair workers' compensation is provided to all victims of asbestos diseases.}, } @article {pmid15281379, year = {2004}, author = {Trosić, I and Milković-Kraus, S}, title = {Asbestosis in the Republic of Croatia.}, journal = {International journal of occupational and environmental health}, volume = {10}, number = {2}, pages = {198-201}, doi = {10.1179/oeh.2004.10.2.198}, pmid = {15281379}, issn = {1077-3525}, mesh = {Asbestosis/economics/*epidemiology/*prevention & control ; Consumer Advocacy ; Croatia/epidemiology ; Humans ; Occupational Exposure/legislation & jurisprudence/prevention & control ; Public Policy ; Workers' Compensation/legislation & jurisprudence ; }, abstract = {Croatians have been exposed to asbestos in the shipbuilding and asbestos-cement industries since 1945. The first cases of asbestosis were reported in 1961; 317 cases were recorded from 1990 to 2000. The Croatian Cancer Registry recorded 248 malignant pleural mesotheliomas between 1991 and 1997, two thirds of which were attributable to occupational exposures to asbestos. The Croatian Asbestosis Patient Association was founded in 1998 to help victims. Croatian law defines the employer's responsibility for work-related health damage and compensation, but average legal proceedings for asbestosis claims take about seven years. Croatian law does not ban the manufacture and import of asbestos. Croatia as a transitional country is subject to socioeconomic pressures. Future approaches to the asbestos issue will depend on revised regulations, which are expected to conform to recommendations of the European Union by 2005.}, } @article {pmid15281378, year = {2004}, author = {Degiovanni, D and Pesce, B and Pondrano, N}, title = {Asbestos in Italy.}, journal = {International journal of occupational and environmental health}, volume = {10}, number = {2}, pages = {193-197}, doi = {10.1179/oeh.2004.10.2.193}, pmid = {15281378}, issn = {1077-3525}, mesh = {Asbestosis/*epidemiology/*history/prevention & control ; Chemical Industry/legislation & jurisprudence ; Comorbidity ; Consumer Advocacy ; History, 20th Century ; Humans ; Incidence ; Italy/epidemiology ; Lung Neoplasms/epidemiology ; Mesothelioma/epidemiology ; Occupational Exposure/history/legislation & jurisprudence/prevention & control ; }, abstract = {Asbestos-related diseases remain common in Italy due to past exposures that were tolerated by a government distracted and manipulated by multinational asbestos corporations. The incidence of asbestos-related cancers has taken on almost epidemic proportions, for example, in Casale Monferrato in northwest Italy, where Eternit remained in operation until 1985, and in Monfalcone in northeast Italy, where naval dockyards and related activities created pollution. Authorities took action only after public protests, trade union pressures, and campaigning by the families of victims. Now that a ban exists in Italy, it is vital that it be fully enforced to reverse the epidemic of mesothelioma, lung cancer, and other asbestos-related diseases.}, } @article {pmid15281377, year = {2004}, author = {Gorman, T and Johnston, R and McIvor, A and Watterson, A}, title = {Asbestos in Scotland.}, journal = {International journal of occupational and environmental health}, volume = {10}, number = {2}, pages = {183-192}, doi = {10.1179/oeh.2004.10.2.183}, pmid = {15281377}, issn = {1077-3525}, mesh = {Asbestosis/economics/*epidemiology/*prevention & control ; Chemical Industry/statistics & numerical data ; Humans ; Occupational Exposure/economics/legislation & jurisprudence/statistics & numerical data ; *Public Policy ; Scotland/epidemiology ; Self-Help Groups/organization & administration ; }, abstract = {This paper outlines the asbestos hazard in Scotland and draws upon a systematic oral history project to analyze from the workers' perspective the nature of exposure, the limitations of government regulatory initiatives, and the ramifications of contracting asbestos-related diseases for sufferers and their families. Current issues are investigated, stressing the agency of workers, trade unions, sympathetic local councils, and, especially, the victims' pressure groups. The occupational and environmental health threats of asbestos in Scotland remain significant, although recent E.U.- and U.K.-based decisions to ban further use of asbestos together with active campaigning by local activist groups have helped to reduce them. Mesothelioma mortality rates remain high, due to historic exposures, and much work remains to be done to reduce the number and plight of asbestos-exposed workers.}, } @article {pmid15281375, year = {2004}, author = {Waterman, YR and Peeters, MG}, title = {The Dutch Institute for Asbestos Victims.}, journal = {International journal of occupational and environmental health}, volume = {10}, number = {2}, pages = {166-176}, doi = {10.1179/oeh.2004.10.2.166}, pmid = {15281375}, issn = {1077-3525}, mesh = {Academies and Institutes/*organization & administration ; Asbestosis/*economics/epidemiology ; Humans ; Negotiating ; Netherlands/epidemiology ; Occupational Exposure/economics/legislation & jurisprudence ; Workers' Compensation/*organization & administration/statistics & numerical data ; }, abstract = {The primary goal of the Dutch Institute for Asbestos Victims is to compensate mesothelioma victims who have been exposed to asbestos in the workplace, while they are still alive, by acting as a neutral mediator between these victims and their (former) employers or their insurers. Representatives of victims, employees, employers, and insurers have agreed to cooperate in the formation and operation of the Institute. The process of reaching a financial settlement has been collectivized, standardized, pacified, and institutionalized. The difficulty of awarding compensation while victims are still alive has led to the Advance Payment Scheme.}, } @article {pmid15281374, year = {2004}, author = {Swuste, P and Burdorf, A and Ruers, B}, title = {Asbestos, asbestos-related diseases, and compensation claims in The Netherlands.}, journal = {International journal of occupational and environmental health}, volume = {10}, number = {2}, pages = {159-165}, doi = {10.1179/oeh.2004.10.2.159}, pmid = {15281374}, issn = {1077-3525}, mesh = {Asbestosis/*economics/*epidemiology/prevention & control ; Humans ; Netherlands/epidemiology ; Occupational Exposure/economics/legislation & jurisprudence/prevention & control/statistics & numerical data ; Registries ; Workers' Compensation/legislation & jurisprudence/*statistics & numerical data ; }, abstract = {In The Netherlands the number of asbestos-related diseases is increasing. An age-cohort model predicts a steep rise in pleural mesothelioma deaths up to 490 cases per year among men, with a total death toll close over 12,000 cases during 2000-2028. In the past decade the number of compensation claims for asbestos-related diseases has more than doubled, with increasingly verdicts in favor of claimants. In addition to the medical information, information about the state of the art of preventive measures in different periods of time plays a decisive role in these claims. The use of asbestos in The Netherlands, the occurrence of asbestos-related diseases, the national asbestos regulations, and the position of the claimants in asbestos lawsuits in The Netherlands are reviewed.}, } @article {pmid15281373, year = {2004}, author = {Hillerdal, G}, title = {The Swedish experience with asbestos: history of use, diseases, legislation, and compensation.}, journal = {International journal of occupational and environmental health}, volume = {10}, number = {2}, pages = {154-158}, doi = {10.1179/oeh.2004.10.2.154}, pmid = {15281373}, issn = {1077-3525}, mesh = {Asbestosis/economics/*epidemiology/prevention & control ; Humans ; Mining/standards ; Occupational Exposure/economics/legislation & jurisprudence/*statistics & numerical data ; Public Policy ; Sweden/epidemiology ; Workers' Compensation/economics/legislation & jurisprudence ; }, abstract = {After World War II, large quantities of asbestos were imported to Sweden and used in construction and ship building. In 1976, the use of asbestos was for practical purposes prohibited. Today, the only exposures are environmental, from asbestos in place and when buildings are demolished or rebuilt, and there are very strict rules for such work. Consequently, it is assumed that the asbestos-related diseases will gradually disappear from society, but due to the long latency time, about 100 mesotheliomas still occur every year in Sweden, and so far there is no certain sign of a decrease in incidence. Compensation is from the state via general insurance and consists basically of compensation for lost income and medical costs.}, } @article {pmid15261439, year = {2004}, author = {Budgen, A}, title = {Asbestos: a clear and present danger--a UK perspective.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {45 Suppl 1}, number = {}, pages = {S77-9}, doi = {10.1016/j.lungcan.2004.04.017}, pmid = {15261439}, issn = {0169-5002}, mesh = {Asbestos/*adverse effects ; Compensation and Redress ; History, 19th Century ; History, 20th Century ; Liability, Legal ; Mesothelioma/*etiology/*history ; *Public Policy ; United Kingdom ; }, abstract = {The hazardous nature of asbestos has been recognised for over a hundred years yet, despite legislation to protect and compensate workers, the battle for adequate compensation continues.}, } @article {pmid15261438, year = {2004}, author = {Haberkorn, U}, title = {Positron emission tomography in the diagnosis of mesothelioma.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {45 Suppl 1}, number = {}, pages = {S73-6}, doi = {10.1016/j.lungcan.2004.04.016}, pmid = {15261438}, issn = {0169-5002}, mesh = {Diagnosis, Differential ; Fluorodeoxyglucose F18 ; Humans ; Magnetic Resonance Imaging ; Mesothelioma/*diagnostic imaging ; Radiopharmaceuticals ; *Tomography, Emission-Computed ; Tomography, X-Ray Computed ; }, abstract = {The increasing incidence of malignant pleural mesothelioma has led to the development of new treatment strategies and a need for new diagnostic techniques to identify the extent of the disease at an early stage and to evaluate treatment. Computed tomography (CT) and magnetic resonance imaging (MRI) are helpful in identifying the location and extent of the involved areas but cannot always differentiate between benign and malignant processes. Fluorodeoxyglucose (FDG)-positron emission tomography (PET) imaging, which in oncology, is based on changes in metabolic pathways of glucose, has been shown in a number of studies to differentiate malign and benign lesions in patients with asbestos exposure. FDG-PET images were also found to provide excellent delineation of the active tumour sites. Further evaluations of this technique included a combined experimental/clinical study to investigate the difference in rates of FDG uptake between malignant and inflammatory cells and processes.}, } @article {pmid15261437, year = {2004}, author = {Entwisle, J}, title = {The use of magnetic resonance imaging in malignant mesothelioma.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {45 Suppl 1}, number = {}, pages = {S69-71}, doi = {10.1016/j.lungcan.2004.04.015}, pmid = {15261437}, issn = {0169-5002}, mesh = {Asbestos/adverse effects ; Diagnosis, Differential ; Humans ; *Magnetic Resonance Imaging ; Mesothelioma/*pathology ; Patient Care Planning ; Pleural Diseases/*pathology ; Pleural Neoplasms/*pathology ; }, abstract = {Magnetic resonance imaging (MRI) is not routinely used in investigations for patients with suspected malignant pleural mesothelioma but it can be a useful tool in some instances--particularly predicting malignancy in patients with asbestos exposure; differentiating between metastatic pleural disease and malignant pleural mesothelioma (MPM); assessing patients for radical surgery and post treatment evaluation of patients.}, } @article {pmid15261430, year = {2004}, author = {Krismann, M and Müller, KM and Jaworska, M and Johnen, G}, title = {Pathological anatomy and molecular pathology.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {45 Suppl 1}, number = {}, pages = {S29-33}, doi = {10.1016/j.lungcan.2004.04.005}, pmid = {15261430}, issn = {0169-5002}, mesh = {Asbestos/*adverse effects ; Biomarkers/*analysis ; DNA/analysis ; DNA-Binding Proteins ; Diagnosis, Differential ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Mesothelioma/diagnosis/*genetics/*pathology ; Prognosis ; Simian virus 40/pathogenicity ; Telomerase/analysis ; Thoracoscopy ; }, abstract = {The incidence of malignant mesotheliomas in Germany has increased since about the mid 1980s, and a further increase is expected until about 2020 due to the peak in asbestos processing in Germany between 1965 and 1980. About 90% of the mesotheliomas recorded in the files of the German Mesothelioma Registry in Bochum are asbestos-related and therefore possibly due to an occupational exposure. In 2003, 717 mesotheliomas were newly diagnosed at the German Mesothelioma Registry. Mesotheliomas are very heterogeneous in terms of histological appearances and of prognosis. At present, the diagnostic gold standard is conventional histology in combination with additional immunohistochemical analysis. We were not able to confirm a promising report that described telomerase reverse transcriptase catalytic subunit (TERT) for the differentiation between reactive and neoplastic mesothelial lesions, which can be extremely difficult. DNA cytometric analysis may also help differentiate between reactive and neoplastic mesothelial lesions. There are some characteristic patterns of chromosomal imbalances as detectable by comparative genomic hybridization (CGH), but at present, specific chromosomal or genetic defects that give rise to a mesothelioma are not known. A reliable pathological diagnosis is the basis for therapeutic, prognostic, and medicolegal consequences. In general, it can be achieved by thoracoscopic inspection with specifically directed biopsy. Furthermore, a description of the peculiarities of each mesothelioma by the pathologist might be the key to a more individual therapy in the future.}, } @article {pmid15261429, year = {2004}, author = {Filiberti, R and Montanaro, F}, title = {Epidemiology of pleural mesothelioma in Italy.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {45 Suppl 1}, number = {}, pages = {S25-7}, doi = {10.1016/j.lungcan.2004.04.011}, pmid = {15261429}, issn = {0169-5002}, mesh = {Aged ; Asbestos/*adverse effects ; *Environmental Exposure ; Humans ; Incidence ; Italy/epidemiology ; Mesothelioma/*epidemiology/*etiology ; Pleural Neoplasms/*epidemiology/*etiology ; Registries/*statistics & numerical data ; }, abstract = {The incidence of malignant mesothelioma (MM) in Italy is increasing and is assumed to be a consequence of high levels of asbestos exposure. Establishment of the National Mesothelioma Registry (ReNaM) and the co-operation of five regional centers has allowed the estimation of the incidence of malignant mesothelioma in major parts of Italy and the definition of exposure to asbestos.}, } @article {pmid15261428, year = {2004}, author = {Musk, AW and de Klerk, NH}, title = {Epidemiology of malignant mesothelioma in Australia.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {45 Suppl 1}, number = {}, pages = {S21-3}, doi = {10.1016/j.lungcan.2004.04.010}, pmid = {15261428}, issn = {0169-5002}, mesh = {Asbestos, Crocidolite/*adverse effects ; Australia/epidemiology ; Cohort Studies ; Epidemiologic Studies ; Humans ; Incidence ; Mesothelioma/*epidemiology/*etiology ; *Occupational Exposure ; Pleural Neoplasms/*epidemiology/*etiology ; }, abstract = {In Australia, consumption of asbestos peaked in about 1975 at around 70,000t per year--the majority being used for asbestos cement manufacture. Chrysotile, amphibole and crocidolite have all been mined in Australia and employment records from the single company which mined most of the crocidolite deposits at Wittenoom have formed the basis of an ongoing cohort mortality study of the workforce.}, } @article {pmid15261427, year = {2004}, author = {Emri, S and Demir, AU}, title = {Malignant pleural mesothelioma in Turkey, 2000-2002.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {45 Suppl 1}, number = {}, pages = {S17-20}, doi = {10.1016/j.lungcan.2004.04.009}, pmid = {15261427}, issn = {0169-5002}, mesh = {Asbestos/*adverse effects ; *Environmental Exposure ; Genetic Predisposition to Disease ; Humans ; Mesothelioma/etiology/*pathology/virology ; Neoplasm Staging/methods ; Pleural Neoplasms/etiology/*pathology/virology ; Prognosis ; Turkey ; Zeolites/*adverse effects ; }, abstract = {Both asbestos and erionite related malignant pleural mesothelioma (MPM) is a serious health problem in Turkey. Erionite has a higher potency in the lung than asbestos and familial clustering of malignant mesothelioma suggests a genetic predisposition to this cancer among affected individuals. Neither Simian virus 40 (SV40) nor human herpes virus 8 (HHV-8) are co-factors in the pathenogenesis of environmentally induced mesothelioma. A survival advantage has been demonstrated in patients with asbestos-induced mesothelioma compared with erionite-induced mesothelioma. This together with the proliferation index (PI) can be used as an independent prognostic factor for patients with malignant pleural mesothelioma. It is envisaged that the application of these prognostic approaches together with the new TNM staging system will allow investigations to be more precisely carried out and evaluated.}, } @article {pmid15261426, year = {2004}, author = {Niklinski, J and Niklinska, W and Chyczewska, E and Laudanski, J and Naumnik, W and Chyczewski, L and Pluygers, E}, title = {The epidemiology of asbestos-related diseases.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {45 Suppl 1}, number = {}, pages = {S7-S15}, doi = {10.1016/j.lungcan.2004.04.008}, pmid = {15261426}, issn = {0169-5002}, mesh = {Asbestos, Crocidolite/*adverse effects ; Asbestosis/complications/*epidemiology/*etiology ; *Environmental Exposure ; Humans ; Manufactured Materials ; Mesothelioma/*epidemiology/*etiology ; Mineral Fibers/adverse effects ; *Occupational Exposure ; Risk Factors ; Time Factors ; }, abstract = {Asbestos has been recognised as a potential health hazard since the 1940s. Of the two major species of asbestos; white asbestos (chrysotile) and blue asbestos (crocidolite), both of which are hazardous. The workers at extraction facilities are at the greatest risk of exposure to asbestos and, therefore, the development of asbestos-related diseases, commonly mesothelioma. However, other individuals at a high risk of exposure include asbestos-cement workers, insulation workers and ship-yard workers. Environmental exposure to asbestos can occur as a result of living in areas either characterised by natural outcrops of asbestos or asbestos-related materials, or those close to asbestos-producing or -using plants. Unfortunately, man-made fibre alternatives to asbestos, such as rock and slag-wool and glass wool, have also been shown to have a detrimental effect on human health. A characteristic of mesothelioma is that there is a long latency period (20-30 years) before the signs and symptoms of the disease become apparent. In addition, diagnosis of the disease can be difficult. The use of biological markers, such as tissue polypeptide antigen, may play a useful role in the early detection of the disease in individuals at risk.}, } @article {pmid15261425, year = {2004}, author = {Abratt, RP and Vorobiof, DA and White, N}, title = {Asbestos and mesothelioma in South Africa.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {45 Suppl 1}, number = {}, pages = {S3-6}, doi = {10.1016/j.lungcan.2004.04.007}, pmid = {15261425}, issn = {0169-5002}, mesh = {Adult ; Asbestos/*adverse effects ; Asbestosis/*complications ; Child ; *Environmental Exposure ; Female ; Humans ; Male ; Mesothelioma/epidemiology/*etiology ; Mining ; South Africa/epidemiology ; }, abstract = {Asbestos has been used by man since 4000 before the Christian era (BCE) in many different parts of the world and for a wide range of functions. Blue asbestos (crocidolite) was first discovered in South Africa in 1805 and within a few years was being mined there extensively. Mining reached its peak in 1977 with >380,000 tons being exported and 20,000 miners employed in the industry. South Africa also has large deposits of white asbestos (chrysotile) and brown asbestos (amosite) both of which have been mined extensively. At the turn of the 20th century, it was noted that those working with asbestos suffered lung disease and in 1960, the link between asbestosis and mesothelioma was established in the Kimberley area of South Africa. Further studies in the 1970s and 1980s showed an alarming incidence of mesothelioma based on pathology reports. The majority of the reported mesothelioma cases result from exposure to asbestos in its many uses in secondary industry although incidence of the condition among miners is also significant. A high proportion of mesothelioma in patients in South Africa is attributed to environmental origin with a high incidence of women and children affected.}, } @article {pmid15255560, year = {2004}, author = {Johansen, C}, title = {Electromagnetic fields and health effects--epidemiologic studies of cancer, diseases of the central nervous system and arrhythmia-related heart disease.}, journal = {Scandinavian journal of work, environment & health}, volume = {30 Suppl 1}, number = {}, pages = {1-30}, pmid = {15255560}, issn = {0355-3140}, mesh = {Adolescent ; Adult ; Arrhythmias, Cardiac/*epidemiology/etiology ; Central Nervous System Diseases/*epidemiology/etiology ; Child ; Cohort Studies ; Electromagnetic Fields/*adverse effects ; Environmental Exposure/*adverse effects ; Female ; Humans ; Male ; Middle Aged ; Neoplasms, Radiation-Induced/*epidemiology ; Risk Assessment ; Scandinavian and Nordic Countries/epidemiology ; }, abstract = {This epidemiologic investigation comprised separate studies of the risk of cancer, cause-specific mortality rates, risks for neurodegenerative diseases, and the risk of arrhythmia-related heart disease among employees exposed to extremely low-frequency (50-Hz) electromagnetic fields (EMF) in the Danish utility industry. All the employees in this industry were followed-up in several registers. The risk of disease was analyzed in relation to occupational exposure to EMF, latency, and duration of employment. A specific job-exposure matrix was developed and validated by comparison with direct measurements of EMF during a workday. Linkage with the Danish Cancer Register did not identify increased risks for the cancers suggested a priori to be associated with exposure to EMF, including leukemia, brain tumors, and breast cancer. Significantly increased risks for lung cancer and mesothelioma were identified for workers highly exposed to asbestos. Linkage with the National Mortality Register revealed a significantly increased overall mortality rate from amyotrophic lateral sclerosis (ALS), with an increasing trend with duration of employment and EMF exposure. In addition, a significantly increased mortality rate from electric accidents was observed. It was hypothesized that the observation of increased mortality from ALS was associated with exposure to EMF or electric shocks. No increased mortality rate from cardiovascular or cerebrovascular disease was observed. Linkage with the National Hospital Register also revealed an increased risk of ALS and, thereby confirmed the finding of an increased mortality rate for this disease in the previous study. Linkage of the cohort with the Multiple Sclerosis Register revealed an increased risk of multiple sclerosis, which was not, however, significant. Linkage with the Pacemaker Register showed no increased risk of severe arrhythmia-related heart disease. The second part of the study included the establishment of a large, nationwide cohort of mobile phone subscribers comprising some 420 000 persons. No increased risk was observed for the cancers considered a priori to be possibly associated with the radiofrequency fields emitted by mobile phones, which were brain tumors, including acoustic neuroma, salivary gland tumors, and leukemia. The data were analyzed by duration of phone use, latency, system used (NMT, GSM or both) and age at first subscription. A study of the incidence of ocular malignant melanoma in comparison with the annual increase among the mobile phone subscribers showed a highly stable incidence rate for this rare cancer in Denmark over close to 50 years of registration. On the basis of these studies and the scientific literature, it is concluded that occupational exposure to 50-Hz EMF is not associated with an increased risk of cancer, but that these fields, electric shocks, or some other unknown factor related to alternating current electricity may be associated with the risk of ALS. There is no clear evidence that 50-Hz EMF is associated with other neurodegenerative or cardiovascular diseases. At present, there is little, if any, evidence that the use of mobile phones is associated with cancer in adults, including brain tumors, acoustic neuroma, cancer of the salivary glands, leukemia, or malignant melanoma of the eye.}, } @article {pmid15254610, year = {2004}, author = {Gulmez, I and Kart, L and Buyukoglan, H and Er, O and Balkanli, S and Ozesmi, M}, title = {Evaluation of malignant mesothelioma in central Anatolia: a study of 67 cases.}, journal = {Canadian respiratory journal}, volume = {11}, number = {4}, pages = {287-290}, doi = {10.1155/2004/204793}, pmid = {15254610}, issn = {1198-2241}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Environmental Exposure ; Female ; Humans ; Male ; Mesothelioma/diagnosis/diagnostic imaging/*epidemiology/etiology ; Middle Aged ; Pleural Effusion/etiology ; Pleural Neoplasms/diagnosis/diagnostic imaging/*epidemiology/etiology ; Tomography, X-Ray Computed ; Turkey/epidemiology ; Zeolites/adverse effects ; }, abstract = {BACKGROUND: Malignant mesothelioma (MM) is a fatal neoplasm which frequently results from exposure to asbestos or erionite.

METHOD: Sixty-seven patients with MM were seen between 1990 and 2001. Their clinical and radiological features, as well as the therapy, were retrospectively evaluated.

RESULTS: In 51 patients (76.1%), the MM was confined to the pleura, in 14 patients it was exclusively peritoneal and in two patients, it involved both areas. Of the 67 cases, 35 (52.2%) were women. The mean (+/- SD) age for all cases was 57.6+/-11.5 years. Dyspnea (67.2%), cough (55.2%) and chest pain (50.7%) were the most frequent symptoms of onset. Pleural effusion (92.4%) was the most common chest x-ray finding, whereas pleural effusion (60.8%), pleural nodules (34.7%) and pleural thickening (34.7%) were the most common computed tomography findings in pleural MM patients. The histological subtypes of MM were determined as epithelial in 60 patients (89.5%), sarcomatous in four patients (5.9%) and mixed in three patients (4.4%). Although 50.7% and 25.4% of the cases were exposed to erionite and asbestos, respectively, 23.9% of the cases recalled no exposure to asbestos or erionite. Exposures were environmental as opposed to occupational. Thirty-five patients (52.2%) were administered chemotherapy, and follow-up data were available for 22 patients. For these patients, the two-year survival rate was 22% and the two-year progression-free interval was 15.7%. There were no differences between patients with asbestos and erionite exposure.

CONCLUSION: MM should be considered when exudative pleural effusion is detected in a patient who has been exposed to asbestos or erionite. MM is a major public health problem in parts of Turkey and compulsory environmental control of fibrous mineral should be considered.}, } @article {pmid15254607, year = {2004}, author = {Anthonisen, NR}, title = {Trouble in Anatolia.}, journal = {Canadian respiratory journal}, volume = {11}, number = {4}, pages = {273-274}, doi = {10.1155/2004/545319}, pmid = {15254607}, issn = {1198-2241}, mesh = {Asbestos/adverse effects ; Environmental Exposure ; Humans ; Mesothelioma/*epidemiology/etiology ; Pleural Neoplasms/*epidemiology/etiology ; Turkey/epidemiology ; }, } @article {pmid15244110, year = {2004}, author = {Savastano, L and Bonacci, S and Saracino, V and Longo, M}, title = {[The association of lung cancer with asbestos and tobacco smoking].}, journal = {La Clinica terapeutica}, volume = {155}, number = {2-3}, pages = {69-74}, pmid = {15244110}, issn = {0009-9074}, mesh = {Air Pollutants, Occupational/adverse effects ; Asbestos/*adverse effects ; Carcinogens/*adverse effects ; Humans ; Italy/epidemiology ; Lung Neoplasms/*epidemiology/*etiology ; Mesothelioma/epidemiology/etiology ; Occupational Diseases/epidemiology/etiology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/epidemiology/etiology ; Smoking/*adverse effects ; Time Factors ; }, abstract = {This work summarises the potential association link for lung cancer between asbestos and smoking. This link emerges not only from different epidemiological and experimental studies, but also from a wide data collection carried out by an omogeneous Italian industrial group. The examination of the data set has led to the conclusion that the simultaneous exposition to asbestos and tobacco's smoke entails a factor, usually multiplicative and also partially additive, in relation to lung cancer; on the other hand, it does not seem to have a great relevance for mesothelioma pleurico. On the basis of this evidence, the Authors focus in particular on the measures of prevention in the contest of work conditions, in order to highlight the impact of the two carcinogenic agents in workers.}, } @article {pmid15216566, year = {2004}, author = {Berg, R}, title = {When science crosses politics, I: The case of naturally occurring asbestos.}, journal = {Journal of environmental health}, volume = {66}, number = {10}, pages = {31-39}, pmid = {15216566}, issn = {0022-0892}, mesh = {Asbestos/*toxicity ; *Decision Making ; Environmental Exposure/*adverse effects ; Environmental Health/*standards ; Hazardous Substances/adverse effects ; Humans ; Mesothelioma/chemically induced/epidemiology ; Mineral Fibers/toxicity ; *Politics ; Risk Assessment ; *Science ; United States ; }, } @article {pmid15209929, year = {2004}, author = {Hessel, PA and Teta, MJ and Goodman, M and Lau, E}, title = {Mesothelioma among brake mechanics: an expanded analysis of a case-control study.}, journal = {Risk analysis : an official publication of the Society for Risk Analysis}, volume = {24}, number = {3}, pages = {547-552}, doi = {10.1111/j.0272-4332.2004.00458.x}, pmid = {15209929}, issn = {0272-4332}, mesh = {Asbestos, Serpentine/*adverse effects/chemistry ; Automobiles ; Case-Control Studies ; Confidence Intervals ; Humans ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; Occupational Exposure ; Odds Ratio ; Particle Size ; Risk Assessment ; United States ; United States Environmental Protection Agency ; }, abstract = {The U.S. Environmental Protection Agency has begun discussions to consider its assessment of asbestos toxicity related to mineral form and fiber size. Brake workers are typically exposed to short chrysotile fibers. To explore the mesothelioma risk among brake workers, considering other occupational exposures to asbestos, data from a study that was published previously were obtained and the analysis was extended. The National Cancer Institute provided data from a case-control study of mesothelioma. Because many participants with a history of brake work also had employment in other asbestos-related occupations, mesothelioma cases and controls were compared for a history of brake work, controlling for employment in eight occupations with potential asbestos exposure. A stratified analysis was also performed excluding those with any of the eight occupations. Possible interactions between brake work and other occupational exposures related to risk of mesothelioma were also examined. The odds ratio (OR) for employment in brake installation or repair was 0.71 (95% CI: 0.30-1.60) when controlled for insulation or shipbuilding. When a history of employment in any of the eight occupations with potential asbestos exposure was controlled, the OR was 0.82 (95% CI: 0.36-1.80). ORs did not increase with increasing duration of brake work. Exclusion of those with any of the eight exposures resulted in an OR of 0.62 (95% CI: 0.01-4.71) for occupational brake work. There was no evidence of an interaction between brake work and other occupational exposures. These latter analyses were based on small numbers of exposed cases. The results are consistent with the existing literature indicating that brake work does not increase the risk of mesothelioma and adds to the evidence that fiber type and size are important determinants of mesothelioma risk.}, } @article {pmid15208818, year = {2004}, author = {Orbaugh, KK}, title = {Nursing considerations for administering pemetrexed (Alimta) in combination with cisplatin for malignant pleural mesothelioma.}, journal = {Clinical journal of oncology nursing}, volume = {8}, number = {3}, pages = {242-247}, doi = {10.1188/04.CJON.242-247}, pmid = {15208818}, issn = {1092-1095}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/*adverse effects ; Cisplatin/administration & dosage ; Clinical Trials, Phase I as Topic ; Clinical Trials, Phase II as Topic ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Female ; Glutamates/administration & dosage ; Guanine/administration & dosage/*analogs & derivatives ; Humans ; Infusions, Intravenous ; Male ; Maximum Tolerated Dose ; Mesothelioma/*drug therapy/*nursing/pathology ; *Nursing Assessment ; Oncology Nursing ; Pemetrexed ; Pleural Neoplasms/*drug therapy/*nursing/pathology ; Prognosis ; Risk Assessment ; Treatment Outcome ; }, abstract = {No known cure exists for malignant pleural mesothelioma (MPM). The prognosis for patients with this relatively rare, asbestos-related malignancy of the pleural lining of the lung is quite poor. MPM treatment includes surgery, radiotherapy, and chemotherapy. Few patients, however, are candidates for surgery or radiotherapy, so chemotherapy is the only option for most patients. A phase III study found that pemetrexed and cisplatin chemotherapy significantly improved survival and had greater antitumor activity than cisplatin alone. The U.S. Food and Drug Administration recently approved pemetrexed with cisplatin for treating MPM. Nurses should become familiar with the proper preparation and administration of pemetrexed, including the necessity of supplementation with folic acid and vitamin B12. As with all drugs, careful attention must be paid to patient selection, laboratory monitoring, contraindications, and appropriate interventions in the event of adverse reactions or overdose.}, } @article {pmid15205315, year = {2004}, author = {Aldieri, E and Orecchia, S and Ghigo, D and Bergandi, L and Riganti, C and Fubini, B and Betta, PG and Bosia, A}, title = {Simian virus 40 infection down-regulates the expression of nitric oxide synthase in human mesothelial cells.}, journal = {Cancer research}, volume = {64}, number = {12}, pages = {4082-4084}, doi = {10.1158/0008-5472.CAN-04-0486}, pmid = {15205315}, issn = {0008-5472}, mesh = {Asbestos, Crocidolite/adverse effects ; Cells, Cultured ; Down-Regulation ; Epithelial Cells/drug effects/*enzymology/*virology ; Humans ; Mesothelioma/*enzymology/etiology/virology ; NF-kappa B/antagonists & inhibitors/metabolism ; Nitric Oxide Synthase/antagonists & inhibitors/*biosynthesis ; Nitric Oxide Synthase Type II ; Polyomavirus Infections/enzymology/virology ; Simian virus 40/*physiology ; Tumor Virus Infections/enzymology/virology ; }, abstract = {The cytotoxic effects of asbestos are partly mediated by the production of free radicals, including nitric oxide (NO). SV40 has been suggested to synergize with asbestos in the pathogenesis of malignant mesothelioma. Crocidolite asbestos fibers induced in human mesothelial and malignant mesothelioma cells a significant increase of NO synthase activity and expression, which was absent in SV40-infected cells. Furthermore, SV40 infection prevented the NF kappa B activation elicited by crocidolite in both mesothelial and mesothelioma cells. These data suggest that SV40, by inhibiting the synthesis of NO, could favor the survival of transformed, potentially neoplastic cells.}, } @article {pmid15202003, year = {2004}, author = {Wang, Y and Faux, SP and Hallden, G and Kirn, DH and Houghton, CE and Lemoine, NR and Patrick, G}, title = {Interleukin-1beta and tumour necrosis factor-alpha promote the transformation of human immortalised mesothelial cells by erionite.}, journal = {International journal of oncology}, volume = {25}, number = {1}, pages = {173-178}, pmid = {15202003}, issn = {1019-6439}, mesh = {Cell Line, Transformed ; Cytokines/pharmacology ; Epithelial Cells/*cytology/drug effects ; Epithelium/drug effects ; Humans ; Interleukin-1/*pharmacology ; Tumor Necrosis Factor-alpha/*pharmacology ; Zeolites/*pharmacology ; }, abstract = {Asbestos fails to induce the transformation of human mesothelial cells in vitro although it has been known as a potential carcinogen to human mesothelial cells. Interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNF-alpha) are major cytokines released by macrophages after inhalation of asbestos. These cytokines can regulate mesothelial cell proliferation both in vitro and in vivo. In the present study, we used the growth in soft agar as an index of transformation and investigated the role of IL-1beta and TNF-alpha during the process of human mesothelial cell carcinogenesis. Both IL-1beta and TNF-alpha were demonstrated to enhance erionite-induced transformation of the immortalised, non-tumorigenic human mesothelial cell line (MeT-5A) in vitro. The MeT-5A cells could only be transformed when the cells were exposed to a combination of cytokines and erionite, or at least two cytokines together without erionite, for at least 4 months in vitro. The findings presented here suggest that IL-1beta and TNF-alpha play a significant role in the pathogenesis of mesothelioma, and that it might be desirable to block or inhibit cytokine secretion in high risk populations to prevent mesothelioma.}, } @article {pmid15197866, year = {2004}, author = {Pylev, LN and Vasil'eva, LA and Krinari, GA}, title = {[Insignificant carcinogenicity of chrysotile asbestos of the Ak-Dovurak deposits in Russia and its possible links].}, journal = {Gigiena i sanitariia}, volume = {}, number = {3}, pages = {72-73}, pmid = {15197866}, issn = {0016-9900}, mesh = {Animals ; Asbestos, Serpentine/*adverse effects ; Catchment Area, Health ; Dust ; Female ; Lung Neoplasms/*chemically induced/pathology ; Lymphoma/*chemically induced/pathology ; Male ; Mesothelioma/*chemically induced/pathology ; *Mining ; Pleural Neoplasms/*chemically induced/pathology ; Rats ; Russia/epidemiology ; Splenic Neoplasms/*chemically induced/pathology ; }, abstract = {Thrice intrapleural injection of 20 mg of dust of the chrysotile from the Ak-Dovurak deposit caused pleural mesothelioma in 10.7% of the rats, which was significantly less than that upon exposure to the chrysotiles from other deposits and amphiboles. The reason for the less carcinogenicity of this chrysotile is the structural features of the surface of its fibrils, namely, its high homogeneity and hence the lack of sites at which the electrically charged centers may be located.}, } @article {pmid15197388, year = {2004}, author = {Pass, HI and Vogelzang, N and Hahn, S and Carbone, M}, title = {Malignant pleural mesothelioma.}, journal = {Current problems in cancer}, volume = {28}, number = {3}, pages = {93-174}, doi = {10.1016/j.currproblcancer.2004.04.001}, pmid = {15197388}, issn = {0147-0272}, mesh = {Antineoplastic Agents/therapeutic use ; Asbestos/adverse effects ; Genes, Tumor Suppressor ; Humans ; *Mesothelioma/diagnosis/etiology/therapy ; Neoadjuvant Therapy ; Oncogenes/genetics ; *Pleural Neoplasms/diagnosis/etiology/therapy ; Radiotherapy, High-Energy ; }, } @article {pmid15188066, year = {2003}, author = {Marta, MJ and Santos Silva, J and Oliveira, A and Saavedra, JA}, title = {[Malignant mesothelioma--a diagnostic challenge].}, journal = {Revista portuguesa de pneumologia}, volume = {9}, number = {5}, pages = {411-425}, doi = {10.1016/s0873-2159(15)30688-7}, pmid = {15188066}, issn = {0873-2159}, mesh = {Aged ; Aged, 80 and over ; Humans ; Lung Neoplasms/*diagnosis ; Male ; Mesothelioma/*diagnosis ; }, abstract = {Malignant mesothelioma is a rare neoplasm associated, in 80% of the cases, with exposure to asbestos fibres, with a latency period between 20 and 50 years. The treatment is palliative in most cases because of the extension of the disease at the time of diagnosis. Mesothelioma is a resistant tumour to chemotherapy and radiotherapy. Overall survival varies between 4 and 18 months, rarely over 5 years. The authors present a case of a 82-year-old man, ex-sailor, with prostatic neoplasm in hormonal "escape" phase, admitted with cough and dyspnea. The chest radiograph showed extensive right pleural effusion. The diagnostic hypothesis were metastatic, infectious and primitive neoplasm origin. Pleural biopsy revealed epithelial malignant mesothelioma confirmed by thoracoscopy, associated with prolongated occupational exposure to asbestos fibres. Without surgery indication the patient was submitted to chemotherapy with gencitabin and cisplatin associated with pleurodesis. Although he improved clinically, the presence of two malignant neoplasms, a rare situation in clinical practice, is associated with a poor prognosis, especially condicionated by the epithelial malignant mesothelioma in Butchart stage II. Finally, we discussed new differential diagnostic techniques with metastatic adenocarcinoma and target therapies under study.}, } @article {pmid15186039, year = {2004}, author = {Laden, F and Stampfer, MJ and Walker, AM}, title = {Lung cancer and mesothelioma among male automobile mechanics: a review.}, journal = {Reviews on environmental health}, volume = {19}, number = {1}, pages = {39-61}, doi = {10.1515/reveh.2004.19.1.39}, pmid = {15186039}, issn = {0048-7554}, support = {T32HL07427/HL/NHLBI NIH HHS/United States ; }, mesh = {Asbestos/*toxicity ; *Automobiles ; Carcinogens/*toxicity ; Humans ; Lung Neoplasms/*etiology ; Male ; Manufactured Materials ; Mesothelioma/*etiology ; Mineral Fibers/toxicity ; Occupational Exposure/*adverse effects ; Research Design ; }, abstract = {BACKGROUND: Extensive, overt asbestos exposure clearly causes lung cancer and mesothelioma. Elevated cancer risk has also been documented for short term or low levels of asbestos exposure. Automobile mechanics are potentially exposed to asbestos through brake repair work. Few studies have specifically examined the risk of lung cancer and mesothelioma associated with exposure to asbestos in brakes, but automobile mechanics are included in many studies of occupation and cancer.

METHODS: We critically reviewed all epidemiologic studies of lung cancer and mesothelioma risk among male automobile mechanics identified through a broadly based Medline search and scrutiny of references in primary and review articles. We discuss the studies grouped by study design and control for smoking, the major risk factor for lung cancer.

RESULTS/CONCLUSIONS: We reviewed all individual analytical studies meeting our criteria, plus all available case series and case reports. When examined in aggregate, the evidence did not support an increase in risk of either lung cancer or mesothelioma among male automobile mechanics occupationally exposed to asbestos from brake repair.}, } @article {pmid15164401, year = {2004}, author = {Greenberg, M}, title = {The doctors and the dockers.}, journal = {American journal of industrial medicine}, volume = {45}, number = {6}, pages = {573-581}, doi = {10.1002/ajim.20011}, pmid = {15164401}, issn = {0271-3586}, mesh = {Asbestos/*history/toxicity ; History, 20th Century ; Humans ; London/epidemiology ; Lung Neoplasms/etiology/*history/mortality ; Mesothelioma/etiology/*history/mortality ; Occupational Diseases/etiology/*history/mortality ; Occupational Exposure/*history ; Occupational Health/history ; Ships/*history ; }, abstract = {BACKGROUND: London Dockers unloading a dusty asbestos cargo in 1965, consulted an eminent Occupational Health physician, Dr. Donald Hunter who informed them that they had been at serious risk. A second, opinion provided jointly by a Consultant Chest Physician, the Port Medical Officer, and the Medical Advisor to the Trades Union Congress, declared that they knew of no disease affecting dockers, and stated that intermittent exposure to asbestos constituted an inconsiderable risk that with certain precautions would be eradicated.

METHODS: Archival material have been obtained to supplement limited published material and eyewitness accounts of the event, to provide a clearer picture of the issues.

RESULTS: Reassured by the Chest Physician, the Port Medical Officer, and the Medical Advisor to the Trades Union Congress that they had little to fear, London dockers resumed unloading asbestos. From time to time dockers at other ports were to express concern and interrupt work, only to be similarly reassured.

CONCLUSIONS: Had the medical troika in 1965 considered the available health statistics, they would have had reason to take a less sanguine attitude to the cancer mortality of dockers. An analysis of data for 16 selected occupations for the years 1900-1902, showed dockers to have an unhealthy job, with deaths from 'All Cancers' of 1.09 per 1,000 years of life (the fourth highest). The Registrar General's occupational mortality report for 1951, noted excess tumors of the lung and stomach for dockers. Elevated Standardized Mortality Ratios for lung cancer had consistently been calculated by the Registrar General for the 20-64 age group of dockers; in 1931 (183), 1951 (149), and 1961 (169): by 1971 it would be 182. A total of 266 dockers were to be registered in the UK by 1999 as having died of malignant mesotheliomas, proving that Donald Hunter's concern for dockers had not been excessive.}, } @article {pmid15148053, year = {2004}, author = {Goodman, M and Teta, MJ and Hessel, PA and Garabrant, DH and Craven, VA and Scrafford, CG and Kelsh, MA}, title = {Mesothelioma and lung cancer among motor vehicle mechanics: a meta-analysis.}, journal = {The Annals of occupational hygiene}, volume = {48}, number = {4}, pages = {309-326}, doi = {10.1093/annhyg/meh022}, pmid = {15148053}, issn = {0003-4878}, mesh = {Asbestos/adverse effects ; Humans ; Lung Neoplasms/*epidemiology/etiology ; Mesothelioma/*epidemiology/etiology ; *Motor Vehicles ; Occupational Diseases/*epidemiology/etiology ; Research Design/standards ; Risk Factors ; Smoking/adverse effects ; }, abstract = {We conducted a systematic review and analysis of the epidemiological literature that examines the risk of lung cancer and mesothelioma among motor vehicle mechanics who may have been engaged in brake repair and, thus, were potentially exposed to asbestos. All relevant studies were classified into three tiers according to their quality. Tier III (lowest quality) studies were cited for completeness, but were not included in the meta-analysis. Meta relative risks (meta-RRs) were calculated for mesothelioma and lung cancer using both fixed and random effects models for Tiers I and II, separately, followed by stratified analyses based on study design or exposure characterization (garage workers versus brake workers) and, for lung cancer studies, based on adequate adjustment for smoking. The meta-analysis for Tier I (higher quality) and Tier II (lower quality) studies of mesothelioma yielded RR estimates of 0.92 (95% CI 0.55-1.56) and 0.81 (95% CI 0.52-1.28), respectively. Further stratification according to exposure characterization did not affect the results. The meta-analysis for lung cancer produced RR estimates of 1.07 (95% CI 0.88-1.31) for Tier I and 1.17 (95% CI 1.01-1.36) for Tier II. When the lung cancer analysis was limited to studies that used adequate control for smoking, the resulting RR estimate was 1.09 (95% CI 0.92-1.28). Based on these findings, we conclude that employment as a motor vehicle mechanic does not increase the risk of developing mesothelioma. Although some studies showed a small increase in risk of lung cancer among motor vehicle mechanics, the data on balance do not support a conclusion that lung cancer risk in this occupational group is related to asbestos exposure.}, } @article {pmid15144777, year = {2004}, author = {DeNardo, P and Bruni, B and Paoletti, L and Pasetto, R and Sirianni, B}, title = {Pulmonary fibre burden in sheep living in the Biancavilla area (Sicily): preliminary results.}, journal = {The Science of the total environment}, volume = {325}, number = {1-3}, pages = {51-58}, doi = {10.1016/j.scitotenv.2003.11.018}, pmid = {15144777}, issn = {0048-9697}, mesh = {Animals ; Asbestos/*analysis/*pharmacokinetics ; Biomarkers/analysis ; Data Collection ; Diffusion ; Electron Probe Microanalysis ; Female ; Humans ; Lung/*chemistry/pathology ; Microscopy, Electron, Scanning ; Mineral Fibers/*analysis ; Public Health ; Risk Assessment ; Sheep ; Sicily ; Tissue Distribution ; }, abstract = {In a national survey on mortality from malignant pleural neoplasms in Italy, aimed at detecting geographic clusters of cases of the disease, the town of Biancavilla, located in a volcanic area of Eastern Sicily, showed high risk of pleural mesothelioma in the absence of occupational asbestos exposure. An environmental survey suggested the stone quarries located in 'Monte Calvario', south-east of the town of Biancavilla, as a possible source of asbestiform fibre exposure. A subsequent crystal-chemistry investigation of the 'Monte Calvario' amphiboles identified the mineral asbestiform fibres as 'fluoro-edenite', a new end-member of the edenite ==> fluoro-edenite series. A collaborative epidemiological and environmental study was initiated to investigate the characteristics of the outbreak of malignant mesothelioma and test the hypothesis of a causal association with exposure to naturally occurring fibres. To investigate if a sheep population could be used to monitor the environmental diffusion of the fibres, we examined lung specimens from 27 culled sheep, at least 3 years old and living near Monte Calvario to check for the presence of fluoro-edenite fibres, using scanning electron microscopy (SEM) analysis and X-ray microanalysis. Fourteen mineral species have been isolated in the mineral particulate matter taken from pulmonary parenchyma, and fluoro-edenite was detected in eight sheep. These preliminary data suggest a possible bio-indicative role of sheep as sentinel animals in the evaluation of environmental fibre diffusion, which merits further investigation.}, } @article {pmid15143397, year = {2003}, author = {Tokat, AO and Kutlay, H}, title = {[Gene therapy in malignant mesothelioma].}, journal = {Tuberkuloz ve toraks}, volume = {51}, number = {4}, pages = {456-460}, pmid = {15143397}, issn = {0494-1373}, mesh = {Genetic Therapy ; Humans ; Mesothelioma/*therapy ; }, abstract = {Malignant mesothelioma which arises from pleural mesothelial cells is a rare and deadly disease. Environmental factors, especially the exposure of asbestos, are accepted as etiological factors. There is not any accepted treatment of malignant mesothelioma. Nowadays four main forms of therapy and the combination of these forms are put in the practise for the treatment of malignant mesothelioma. These are surgical therapy, chemotherapy protocols, radiotherapy protocols and recently immunologic therapy which is based on direct antiproliferative effect of interferon. Gene therapy has been studying experimentally for recent years. The main principles of the gene therapy is sensitizing to antiviral drugs by infecting and changing the gene structure of the malign cells. The most used gene is herpes simplex virus (HSV) tk gene. In malignant mesothelioma, there is no standard treatment protocol and the main cause of death is local spread of tumor and the pathological effects of its mass rather than metastasis and the diagnosis and treatment results are evaluated from the same localization (pleural space). According of these factors, gene therapy could be an appropriate treatment for malignant mesothelioma.}, } @article {pmid15138703, year = {2004}, author = {Verhoff, MA and Risse, M and Alles, JU and Müller, KM and Stachetzki, U}, title = {[Obligation to report occupational diseases. Importance of external post-mortem examinations before cremation].}, journal = {Der Pathologe}, volume = {25}, number = {3}, pages = {217-221}, pmid = {15138703}, issn = {0172-8113}, mesh = {Germany ; Humans ; *Legislation, Medical ; Mortuary Practice ; Occupational Diseases/mortality/*pathology ; Postmortem Changes ; Social Responsibility ; }, abstract = {The practical use of the legally required documentation of occupational diseases is demonstrated by a case of asbestos-related pleural mesothelioma. During the mandatory inquest before cremation, information of manifest pleural mesothelioma had been relayed to the widow of the patient, and an investigation for a possible occupational disease was performed. Reconstruction of the case showed that in the course of 3 months at least 13 physicians had been involved in in-hospital as well as ambulatory therapeutic measures. Until death, none of them informed the trade association about a suspected occupational disease in accordance with BK 4105 of the codex of occupational diseases, although the diagnosis of manifest pleural mesothelioma had been histologically confirmed already 10 weeks prior to the death of the patient. This case demonstrates obvious and evident deficiencies in applying the Code of Social Law VII, which requires physicians to report occupational diseases. In addition, it shows the importance of the post-mortem examination as a control function before cremation.}, } @article {pmid15133442, year = {2004}, author = {Giudicelli, R}, title = {[Surgery for malignant pleural mesothelioma].}, journal = {Revue de pneumologie clinique}, volume = {60}, number = {2}, pages = {68-72}, doi = {10.1016/s0761-8417(04)73472-0}, pmid = {15133442}, issn = {0761-8417}, mesh = {Antineoplastic Combined Chemotherapy Protocols/administration & dosage/*therapeutic use ; Chemotherapy, Adjuvant ; Combined Modality Therapy ; Humans ; Incidence ; Mesothelioma/*drug therapy/epidemiology/*surgery ; *Neoplasm Staging ; Palliative Care ; Pleural Neoplasms/*drug therapy/epidemiology/*surgery ; Prognosis ; Radiotherapy, Adjuvant ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive cancer of the pleura that is usually caused by exposure to asbestos. The incidence of MPM has risen for some decades and is expected to peak between 2010 and 2020. Current surgical treatment involves in a multimodality regimen with radiation and multiple-drug chemotherapy. All currently proposed therapeutic strategies are in total agreement with the international Mesothelioma Interest Group TNM staging system. Schematically: for stage Ia (early stage disease), the therapeutic approach is generally neo-adjuvant intrapleural treatment using cytikines followed by surgical pleurectomy; for more advanced disease (stage Ib, II and III), a multimodal treatment combining extra-pleural pneumonectomy, radiotherapy and multiple-drug chemotherapy, including in all cases cisplatin, is proposed. Recently, results using this multiple modality approach have been favorable especially for patients with epithelial histology, negative resection margins and no metastases to extrapleural lymph nodes; for stage IV (unresectable tumor), palliative treatment is indicated. Early results have been encouraging and the use of recent drugs should allow more optimal treatment.}, } @article {pmid15132064, year = {2004}, author = {Dunleavey, R}, title = {Malignant mesothelioma: risk factors and current management.}, journal = {Nursing times}, volume = {100}, number = {16}, pages = {40-43}, pmid = {15132064}, issn = {0954-7762}, mesh = {Asbestos/adverse effects ; Humans ; *Mesothelioma/diagnosis/etiology/nursing/therapy ; *Peritoneal Neoplasms/diagnosis/etiology/nursing/therapy ; *Pleural Neoplasms/diagnosis/etiology/nursing/therapy ; }, abstract = {Malignant mesothelioma is a cancer of the pleura and peritoneum often associated with asbestos exposure. Although rare its incidence is increasing, principally as a result of the long latency period of the disease. This article presents a review of mesothelioma, looking at the disease process, risk factors, causes, and current management strategies--namely surgery, chemotherapy, and radiotherapy. Some of the nursing implications are discussed along with the resources currently available to patients with mesothelioma in the UK.}, } @article {pmid15128174, year = {2004}, author = {Bianchi, C and Brollo, A and Ramani, L and Bianchi, T and Giarelli, L}, title = {Familial mesothelioma of the pleura--a report of 40 cases.}, journal = {Industrial health}, volume = {42}, number = {2}, pages = {235-239}, doi = {10.2486/indhealth.42.235}, pmid = {15128174}, issn = {0019-8366}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestosis/epidemiology ; Female ; Humans ; Italy/epidemiology ; Male ; Mesothelioma/diagnosis/*epidemiology/*genetics ; Middle Aged ; Occupational Exposure/statistics & numerical data ; Pleural Neoplasms/diagnosis/*epidemiology/*genetics ; }, abstract = {A survey of 610 pleural mesotheliomas disclosed 40 familial cases. The diagnosis was histologically based in 39 cases, and confirmed by necropsy in 30. Occupational data were collected from the patients or from their relatives by personal interviews. Routine lung sections were examined for asbestos bodies in 32 cases. In 15 cases asbestos bodies were isolated after chemical digestion of lung tissue. Familial mesotheliomas included 31 men and 9 women (age range 44-93 yr, mean 70.7, median 71.0). In 15 families there were blood relations between (or among) the members involved. All the patients had been exposed to asbestos, mostly in the shipyards. Asbestos bodies were found on routine lung sections in 27 cases. Asbestos bodies after isolation ranged from 70 bodies to about 900,000/g dried lung tissue. Latency periods (time intervals between first exposure to asbestos and diagnosis) ranged between 25 and 70 yr (mean 52.0, median 54.0). The occurrence of mesothelioma among subjects with blood relations suggests that genetic factors might play a role in determining the susceptibility to asbestos-related cancer. Familial cases among persons without blood relations raise the question if environmental factors that members of a family share, may act as co-factors in asbestos-related mesothelioma.}, } @article {pmid15121517, year = {2004}, author = {Landrigan, PJ and Lioy, PJ and Thurston, G and Berkowitz, G and Chen, LC and Chillrud, SN and Gavett, SH and Georgopoulos, PG and Geyh, AS and Levin, S and Perera, F and Rappaport, SM and Small, C and , }, title = {Health and environmental consequences of the world trade center disaster.}, journal = {Environmental health perspectives}, volume = {112}, number = {6}, pages = {731-739}, pmid = {15121517}, issn = {0091-6765}, support = {P30 ES00260/ES/NIEHS NIH HHS/United States ; P30ES09089-04S/ES/NIEHS NIH HHS/United States ; P30 ES03819/ES/NIEHS NIH HHS/United States ; P30 ES05022/ES/NIEHS NIH HHS/United States ; P42ES07384/ES/NIEHS NIH HHS/United States ; P42ES05948/ES/NIEHS NIH HHS/United States ; P30 ES009089/ES/NIEHS NIH HHS/United States ; }, mesh = {Adult ; *Aircraft ; Animals ; *Construction Materials ; *Environmental Exposure ; Female ; Humans ; Hydrogen-Ion Concentration ; Incidence ; Infant, Newborn ; Infant, Small for Gestational Age ; Lung/immunology/pathology ; Male ; Mice ; Middle Aged ; New York City ; *Occupational Exposure ; Polycyclic Aromatic Hydrocarbons/analysis/poisoning ; Pregnancy ; Prevalence ; Respiratory Tract Diseases/epidemiology/*etiology ; Risk Assessment ; *Terrorism ; }, abstract = {The attack on the World Trade Center (WTC) created an acute environmental disaster of enormous magnitude. This study characterizes the environmental exposures resulting from destruction of the WTC and assesses their effects on health. Methods include ambient air sampling; analyses of outdoor and indoor settled dust; high-altitude imaging and modeling of the atmospheric plume; inhalation studies of WTC dust in mice; and clinical examinations, community surveys, and prospective epidemiologic studies of exposed populations. WTC dust was found to consist predominantly (95%) of coarse particles and contained pulverized cement, glass fibers, asbestos, lead, polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and polychlorinated furans and dioxins. Airborne particulate levels were highest immediately after the attack and declined thereafter. Particulate levels decreased sharply with distance from the WTC. Dust pH was highly alkaline (pH 9.0-11.0). Mice exposed to WTC dust showed only moderate pulmonary inflammation but marked bronchial hyperreactivity. Evaluation of 10,116 firefighters showed exposure-related increases in cough and bronchial hyperreactivity. Evaluation of 183 cleanup workers showed new-onset cough (33%), wheeze (18%), and phlegm production (24%). Increased frequency of new-onset cough, wheeze, and shortness of breath were also observed in community residents. Follow-up of 182 pregnant women who were either inside or near the WTC on 11 September showed a 2-fold increase in small-for-gestational-age (SGA) infants. In summary, environmental exposures after the WTC disaster were associated with significant adverse effects on health. The high alkalinity of WTC dust produced bronchial hyperreactivity, persistent cough, and increased risk of asthma. Plausible causes of the observed increase in SGA infants include maternal exposures to PAH and particulates. Future risk of mesothelioma may be increased, particularly among workers and volunteers exposed occupationally to asbestos. Continuing follow-up of all exposed populations is required to document the long-term consequences of the disaster.}, } @article {pmid15117619, year = {2004}, author = {Villena Garrido, V and López Encuentra, A and Echave-Sustaeta, J and Alvarez Martínez, C and Rey Terrón, L and Sotelo, MT and Ballestín, C}, title = {[Pleural mesothelioma: experience with 62 cases in 9 years].}, journal = {Archivos de bronconeumologia}, volume = {40}, number = {5}, pages = {203-208}, pmid = {15117619}, issn = {0300-2896}, mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; *Mesothelioma/diagnosis/mortality/therapy ; Middle Aged ; *Pleural Neoplasms/diagnosis/mortality/therapy ; Survival Rate ; Time Factors ; }, abstract = {OBJECTIVES: To describe the diagnostic approach, clinical and radiological characteristics, and survival of patients with pleural mesothelioma treated in our hospital over a 9-year period.

PATIENTS AND METHOD: All patients with a diagnosis of pleural mesothelioma diagnosed in our hospital from January 1992 through December 2000 were studied.

RESULTS: Sixty-two patients (49 men) with a mean age of 65 years (range, 45-85) were diagnosed. Probable or known contact with asbestos was established for 41 patients (66%). Ninety-four percent of the patients had chest pain or dyspnea at the onset of clinical assessment. The tumor was situated in the right hemithorax in 33 patients; 59 patients had pleural effusion, and 3 only had pleural thickening. The pleural fluid was bloody in 19% of patients, glucose levels were less than 60 mg/dL in 44%, and the pH of pleural fluid was less than 7.20 in 19%. The diagnosis was established by pleural biopsy for 52%, and by thoracoscopy or thoracotomy for 44%. The median survival was 11 months (95% confidence interval, 8-15); the probability of survival was 0.22 after 2 years, and 0.09 after 5. For the subgroup of patients with epithelial tumors the probability of survival was 0.31 after 2 years and 0.16 after 5 years. In the univariate analysis the predictors of survival were general clinical status (Karnofsky scale), platelet count, serum albumin level, pleural pH, glucose and lactate dehydrogenase levels, and histological type.

CONCLUSIONS: The clinical, radiological, and biochemical characteristics of the pleural fluid from patients with pleural mesothelioma and their survival rate were described.}, } @article {pmid15117424, year = {2004}, author = {Carbone, M and Rdzanek, MA}, title = {Pathogenesis of malignant mesothelioma.}, journal = {Clinical lung cancer}, volume = {5 Suppl 2}, number = {}, pages = {S46-50}, doi = {10.3816/clc.2004.s.002}, pmid = {15117424}, issn = {1525-7304}, support = {R01 LU8271//PHS HHS/United States ; }, mesh = {Animals ; Asbestos/toxicity ; Carcinogens/toxicity ; Humans ; Mesothelioma/etiology/*physiopathology/therapy ; Occupational Diseases/etiology/physiopathology ; Occupational Exposure/adverse effects ; Pleural Neoplasms/etiology/*physiopathology/therapy ; Sex Factors ; Simian virus 40 ; Tumor Virus Infections/etiology/therapy ; Viral Vaccines/administration & dosage ; }, abstract = {Malignant mesothelioma (MM) is a very aggressive tumor that is caused by environmental, biologic, and genetic factors. Among these factors, asbestos plays a major role. The link between asbestos and MM has been firmly established through numerous epidemiologic studies conducted during the past 40 years. However, the causal role of chrysotile asbestos compared with crocidolite asbestos in MM, the method of correctly establishing asbestos exposure, the amount of asbestos necessary to cause MM, and the mechanisms of asbestos tumorigenicity are still being debated. Along with asbestos, Simian virus 40 (SV40), a DNA monkey virus, has recently been implicated in the etiology of MM. Simian virus 40 large T antigen (Tag) and small t antigen (tag) are largely responsible for the carcinogenicity of the virus, and it is possible that SV40 and asbestos are cocarcinogens. Finally, a genetic factor identified in 3 villages in Cappadocia, Turkey, where 50% of individuals die of MM, appears to be the cause of a high incidence of the disease. In these villages, genetic predisposition for MM works together with erionite, a nonasbestos fiber found in the stones used in construction of houses. The diagnosis of MM is made histologically and confirmed through electron microscopy and immunohistochemistry. Currently available therapies for MM prolong survival by a few months at most. An SV40 vaccine is being developed for human use and it is hoped that it may reduce the incidence of MM in asbestos workers.}, } @article {pmid15112747, year = {2004}, author = {Palange, S and Ascoli, V and Carnovale-Scalzo, C and Forastiere, F and D'Ippoliti, D and Presti, EL and Di Domenicantonio, R and Pasetto, R and Perucci, CA}, title = {[Estimates of pleural mesothelioma incidence in the Lazio region (Italy), 1997-2000].}, journal = {La Medicina del lavoro}, volume = {95}, number = {1}, pages = {45-54}, pmid = {15112747}, issn = {0025-7818}, mesh = {Asbestos/adverse effects ; Female ; Hospitals, Public/statistics & numerical data ; Humans ; Incidence ; International Classification of Diseases ; Italy/epidemiology ; Male ; Mesothelioma/diagnosis/*epidemiology/etiology ; Patient Admission/statistics & numerical data ; Pleural Neoplasms/diagnosis/*epidemiology/etiology ; Registries/statistics & numerical data ; Rome/epidemiology ; Sex Distribution ; Urban Population ; }, abstract = {BACKGROUND: Malignant mesothelioma is indicative of past exposure to asbestos. In recent years an increase of incidence and mortality from malignant mesothelioma has been observed. Recent legislation in Italy requires nation-wide registration of asbestos-related pathologies. We conducted a preparatory study for systematic recording of cases of malignant pleural mesothelioma in the Lazio region.

OBJECTIVES: To register new diagnoses of malignant mesothelioma, to estimate the incidence in the Lazio region, and to evaluate possible survey instruments.

METHODS: We conducted a systematic study of hospital admissions in the region with diagnosis of cancer of the pleura (ICD-IX 163) in the period 1997-2000. Clinical information and results of diagnostic tests were requested for 530 patients from the hospitals involved. Using the capture-recapture method, it was possible to estimate the accuracy of the data we compiled using hospital admissions as the data source (76.8%, 95% C.I.=76.4-77.3).

RESULTS: After careful review of clinical documentation, the diagnosis of malignant mesothelioma of the pleura was confirmed in 31.6% of cases (156 cases diagnosed). The percentage of confirmed cases has risen over the years (from 21% in 1997 to 45.1% in 2000) and it was higher in large public hospitals than in other types of health care facilities. On the basis of 156 confirmed cases of mesothelioma (116 males and 40 females), we estimated the annual incidence of the disease in the Lazio region as 1.73 new cases per 100,000 inhabitants among men and 0.47 new cases per 100,000 inhabitants among women.

CONCLUSIONS: The results show that the incidence of mesothelioma in the region is consistent with national data, falling in the middle of the range for all Italian regions. However, some areas emerge (for example, Colleferro, Civitavecchia, Tarquinia, Ferentino, Gaeta, Aprilia, Pomezia) that have particularly high rates, probably in relation to past occupational asbestos exposure. The role of diffuse environmental exposure in Rome may warrant further investigation.}, } @article {pmid15112744, year = {2004}, author = {Romeo, R and Scancarello, G and Cassano, P and Cioni, F and Bacaloni, A and Sartorelli, P}, title = {[Assessment of asbestos exposure via mineralogical analysis of bronchoalveolar lavage fluid].}, journal = {La Medicina del lavoro}, volume = {95}, number = {1}, pages = {17-31}, pmid = {15112744}, issn = {0025-7818}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*analysis ; Asbestosis/epidemiology ; Bronchoalveolar Lavage Fluid/*chemistry ; Bronchoscopy ; Electron Probe Microanalysis ; Environmental Exposure ; Female ; Humans ; Italy/epidemiology ; Lung Neoplasms/epidemiology/etiology ; Male ; Mesothelioma/epidemiology/etiology ; Microscopy, Electron ; Middle Aged ; Mineral Fibers/*analysis ; Occupational Diseases/epidemiology/etiology ; *Occupational Exposure ; Sensitivity and Specificity ; Time Factors ; }, abstract = {BACKGROUND: Mineralogical analysis of bronchoalveolar lavage fluid (BALF) by electron microscopy could be the most suitable method for assessing asbestos exposure. However, it has been claimed that there is not a standardized or systematic approach to the subject of mineralogical analysis.

OBJECTIVES: The aim of the study was to evaluate mineralogical analysis of BALF by transmission electron microscopy (TEM) as biomarker of asbestos fibre load.

METHODS: BALF was examined in 193 exposed workers (189 men and 4 women) and in 84 patients (65 men and 19 women) who underwent diagnostic fibreoptic bronchoscopy for various clinical purposes. Asbestos bodies (AB) in BALF were counted with a phase contrast microscope, while fibres were counted and analysed by TEM.

RESULTS: Fibre counting by TEM showed a significant difference in the two populations (two tailed Mann-Whitney U test, p=0.0044), since it was positive in all exposed subjects. Only 75.1% of the exposed population was positive for asbestos bodies (AB). Subjects who had been exposed over a long time period had higher concentrations of fibres than subjects who had been exposed more recently probably because of higher exposure in the past.

CONCLUSIONS: The study confirms the results of a previous study on a limited number of subjects. Fibre concentrations in BALF can be considered as a reliable biomarker of past asbestos exposure even after many years after cessation of exposure.}, } @article {pmid15107980, year = {2004}, author = {Kraus, T and Müller-Lux, A}, title = {[Occupation related thoracic tumors].}, journal = {Der Radiologe}, volume = {44}, number = {5}, pages = {427-434}, pmid = {15107980}, issn = {0033-832X}, mesh = {Asbestosis/*epidemiology ; Comorbidity ; Germany/epidemiology ; Humans ; Mandatory Reporting ; Neoplasms, Mesothelial/*epidemiology ; Neoplasms, Radiation-Induced/*epidemiology ; Occupational Diseases/*epidemiology ; Occupational Exposure/statistics & numerical data ; *Radon ; Risk Assessment/methods ; Risk Factors ; Silicosis/*epidemiology ; Thoracic Neoplasms/*epidemiology ; }, abstract = {It is estimated that about 4% of cancer mortality is attributed to occupational risk factors. Due to long latency periods it is often difficult to establish causal relationships. Thoracal cancer accounts for about 88% of all compensated occupational cancers in Germany. Most important exposures and diseases are asbestos-related lung cancer, asbestos-related malignant mesothelioma and radiation induced lung cancer (by Radon and its decay products). Lung cancer caused by nickel compounds, hexavalent chromium, arsenic and its compounds, coke oven gases and polycyclic aromatic hydrocarbons are rare. Silica-dust induced lung cancer can be compensated as occupational disease if a silicosis is present. In Germany every physician is obliged to notify a suspected occupational cancer as well as other occupational diseases.}, } @article {pmid15107826, year = {2004}, author = {Apostolou, S and Klein, JO and Mitsuuchi, Y and Shetler, JN and Poulikakos, PI and Jhanwar, SC and Kruger, WD and Testa, JR}, title = {Growth inhibition and induction of apoptosis in mesothelioma cells by selenium and dependence on selenoprotein SEP15 genotype.}, journal = {Oncogene}, volume = {23}, number = {29}, pages = {5032-5040}, doi = {10.1038/sj.onc.1207683}, pmid = {15107826}, issn = {0950-9232}, support = {CA-06927/CA/NCI NIH HHS/United States ; CA-45745/CA/NCI NIH HHS/United States ; }, mesh = {Apoptosis ; Cell Division/drug effects/genetics ; Down-Regulation ; Gene Frequency ; Genetic Variation ; Genotype ; Humans ; Loss of Heterozygosity ; Mesothelioma/*genetics/pathology ; Proteins/*genetics ; RNA, Small Interfering/pharmacology ; Selenium/*pharmacology ; Selenoproteins ; Transfection ; Tumor Cells, Cultured ; }, abstract = {Malignant mesotheliomas (MMs) are aggressive tumors derived from mesothelial cells lining the lungs, pericardium and peritoneum, and are often associated with occupational asbestos exposure. Suppression subtractive hybridization was used to identify genes differentially expressed in MM cells compared to normal mesothelial cells. A gene, SEP15, encoding a 15-kDa selenium-containing protein was isolated using this approach and was subsequently shown to be downregulated in approximately 60% of MM cell lines and tumor specimens. A SEP15 polymorphic variant, 1125A, resides in the SECIS recognition element in the 3'-UTR and may influence the efficiency of Sec incorporation into the protein during translation. Since previous studies have implicated a potential role of the trace element selenium as a chemopreventive agent in animal models and in several types of human cancer, we investigated the effect of selenium on MM cells and its dependence on SEP15 genotype. Selenium was shown to inhibit cell growth and induce apoptosis in a dose-dependent manner in MM cells but had minimal effect on normal mesothelial cells. However, MM cells with downregulated SEP15 or the 1125A variant were somewhat less responsive to the growth inhibitory and apoptotic effects of selenium than MM cells expressing wild-type protein. RNAi-based knockdown studies demonstrated that SEP15 inhibition makes sensitive MM cells more resistant to selenium. These data imply that selenium may be useful as a chemopreventive agent in individuals at high risk of MM due to asbestos exposure, although those with the 1125A polymorphism may be less responsive to the protective benefits of dietary selenium supplementation.}, } @article {pmid15101219, year = {2004}, author = {Albin, M}, title = {[Authorities' risk assessment was influenced by the asbestos industry. The chemicals legislation proposed by the European Union makes the question of independent expertise a current issue].}, journal = {Lakartidningen}, volume = {101}, number = {14}, pages = {1306-1309}, pmid = {15101219}, issn = {0023-7205}, mesh = {Air Pollutants, Occupational/adverse effects ; Asbestos/*adverse effects ; Asbestosis/epidemiology/etiology/prevention & control ; Carcinogens/*adverse effects ; Conflict of Interest ; Europe/epidemiology ; European Union ; Humans ; *Industry/ethics/legislation & jurisprudence ; Lung Neoplasms/epidemiology/etiology/prevention & control ; Mesothelioma/epidemiology/etiology/prevention & control ; Occupational Exposure/adverse effects/ethics/*legislation & jurisprudence ; *Risk Assessment/ethics ; Risk Management/ethics/*legislation & jurisprudence ; *Truth Disclosure/ethics ; United States/epidemiology ; }, } @article {pmid15101205, year = {2004}, author = {Il'icheva, SA and Zaridze, DG}, title = {[Etiological aspects of occupational cancer in printing industry].}, journal = {Vestnik Rossiiskoi akademii meditsinskikh nauk}, volume = {}, number = {2}, pages = {25-29}, pmid = {15101205}, issn = {0869-6047}, mesh = {Asbestos/adverse effects ; Benzene/adverse effects ; Female ; Humans ; Male ; Melanoma/chemically induced/epidemiology ; Mesothelioma/chemically induced/epidemiology ; Neoplasms/*chemically induced/epidemiology ; Occupational Diseases/*chemically induced/epidemiology ; Polycyclic Aromatic Hydrocarbons/adverse effects ; *Printing ; Sex Factors ; }, abstract = {Research of oncology lethality from workplace exposures is one of the most effective approaches to studying the etiology of malignant neoplasms. However, certain problems of methodology compromise the informative value of such research whose purpose is to identify the carcinogens. Addition of data on morbidity and lethality in heterogeneous industrial categories, whose typical feature are inhomogeneous exposures, is a major methodological problem. The fact that the studied occupational populations are limited to male subjects is another important problem. The most adequate epidemiological study projects were analyzed and compared with the results of our own case study, which dealt, for the first time in the history of our country, with investigating the lethality causes of 1552 males and 3473 females occupied as compositors, printers and bookbinders at two major printing enterprises in the city of Moscow. According to the authors, an exposure to polycyclic aromatic hydrocarbons, e.g. benzopirin, could be a reliably higher risk of mortality of melanoma and of ovarian cancer among female press operators. With regard for experimental and epidemiological research, the authors believe it appropriate to put forward the below hypothesis: a many-year exposure to minimal quantities of asbestos contained in the paper dust was the key trigger inducing the malignant mesothelioma and ovarian cancer in bookbinders and printers.}, } @article {pmid15090665, year = {2004}, author = {Weill, H and Hughes, JM and Churg, AM}, title = {Changing trends in US mesothelioma incidence.}, journal = {Occupational and environmental medicine}, volume = {61}, number = {5}, pages = {438-441}, pmid = {15090665}, issn = {1470-7926}, mesh = {Asbestos/adverse effects ; Forecasting ; Humans ; Incidence ; Male ; Mesothelioma/*epidemiology/etiology ; Pleural Neoplasms/*epidemiology/etiology ; SEER Program ; United States/epidemiology ; }, abstract = {AIMS: To report the temporal pattern and change in trend of mesothelioma incidence in the United States since 1973.

METHODS: The Surveillance, Epidemiology, and End Results (SEER) programme of the National Cancer Institute has since 1973 provided annual age adjusted incidence for mesothelioma in representative cancer registries dispersed throughout the USA. SEER data are analysed to describe the trend of male mesothelioma incidence in the USA.

RESULTS: The US male mesothelioma incidence data indicate that after two decades of increasing incidence, a likely decline has been observed since the early 1990s, when a highly significant change in the upward course occurred.

CONCLUSIONS: Increasing male mesothelioma incidence for many years was undoubtedly the result of exposure to asbestos. The high mesothelioma risk was prominently influenced by exposure to amphibole asbestos (crocidolite and amosite), which reached its peak usage in the 1960s and thereafter declined. A differing pattern in some other countries (continuing rise in incidence) may be related to their greater and later amphibole use, particularly crocidolite. The known latency period for the development of this tumour provides biological plausibility for the recent decline in mesothelioma incidence in the USA. This favourable finding is contrary to a widespread fear that asbestos related health effects will show an inevitable increase in coming years, or even decades.}, } @article {pmid15087673, year = {2004}, author = {Galateau-Sallé, F and Vignaud, JM and Burke, L and Gibbs, A and Brambilla, E and Attanoos, R and Goldberg, M and Launoy, G and , }, title = {Well-differentiated papillary mesothelioma of the pleura: a series of 24 cases.}, journal = {The American journal of surgical pathology}, volume = {28}, number = {4}, pages = {534-540}, doi = {10.1097/00000478-200404000-00013}, pmid = {15087673}, issn = {0147-5185}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Female ; Humans ; Male ; Mesothelioma/etiology/*pathology ; Middle Aged ; Occupational Diseases/etiology/pathology ; Occupational Exposure/adverse effects ; Pleural Neoplasms/etiology/*pathology ; Prognosis ; }, abstract = {Well-differentiated papillary mesothelioma (WDPM) of the pleura represents a distinct mesothelial tumor presenting with unilateral pleural effusion and superficial spreading of stout papillary formations with myxoid cores, lined by bland, flattened, or epithelioid cells, without or with limited invasion of the submesothelial layer. The majority of cases have been reported in the peritoneum in women of reproductive age with no history of asbestos exposure and also in the tunica vaginalis of men. We report 24 cases of pleural WDPM and compared their histologic, epidemiologic, and clinical features with those of classic mesothelioma. Men and women were equally affected, with a mean age of 60 years. Half of the patients had a history of occupational asbestos exposure. In 11 patients with a minimal follow-up period of 24 months, the survival ranged from 36 to 180 months with an average of 74 months as compared with 9.89 months for 1248 paired patients with diffuse malignant mesothelioma. Ten-year survival was 30.8%. We conclude that WDPM is a rare and unusual mesothelial tumor, characterized by a lack of deep invasion and associated with an indolent clinical course and long survival. For these reasons, WDPM is best considered as a specific clinico-pathologic entity distinct from conventional diffuse malignant mesothelioma.}, } @article {pmid15070795, year = {2004}, author = {Cornia, PB and Lipsky, BA and Dhaliwal, G and Saint, S}, title = {Clinical problem-solving. Red snapper or crab?.}, journal = {The New England journal of medicine}, volume = {350}, number = {14}, pages = {1443-1448}, doi = {10.1056/NEJMcps032443}, pmid = {15070795}, issn = {1533-4406}, support = {P20-HS11540/HS/AHRQ HHS/United States ; }, mesh = {Aged ; Asbestos/adverse effects ; Ascites/etiology ; Diagnosis, Differential ; Dyspnea/etiology ; Humans ; Jugular Veins/diagnostic imaging ; Lung/diagnostic imaging ; Male ; Mesothelioma/complications/*diagnosis ; Military Personnel ; Occupational Diseases/diagnosis ; Omentum/diagnostic imaging/*pathology ; Paracentesis ; Peritoneal Neoplasms/complications/*diagnosis ; Pleural Effusion/etiology/microbiology ; Thrombosis/complications/diagnostic imaging ; Tomography, X-Ray Computed ; Tuberculin Test ; Tuberculosis, Pulmonary/diagnosis ; }, } @article {pmid15070024, year = {2004}, author = {Henderson, DW and Jones, ML and De Klerk, N and Leigh, J and Musk, AW and Shilkin, KB and Williams, VM}, title = {The diagnosis and attribution of asbestos-related diseases in an Australian context: report of the Adelaide Workshop on Asbestos-Related Diseases. October 6-7, 2000.}, journal = {International journal of occupational and environmental health}, volume = {10}, number = {1}, pages = {40-46}, doi = {10.1179/oeh.2004.10.1.40}, pmid = {15070024}, issn = {1077-3525}, mesh = {Asbestos/*adverse effects ; Asbestosis/epidemiology/etiology ; Australia/epidemiology ; Causality ; Environmental Pollutants/*toxicity ; Humans ; Lung Neoplasms/chemically induced/epidemiology ; Mesothelioma/chemically induced/epidemiology ; Mineral Fibers/adverse effects ; Occupational Diseases/chemically induced/epidemiology ; Occupational Exposure/*adverse effects ; Peritoneal Neoplasms/chemically induced/epidemiology ; Pleural Neoplasms/chemically induced/epidemiology ; Pulmonary Fibrosis/chemically induced/epidemiology ; Tomography, X-Ray Computed ; }, abstract = {Predictions of future cases of mesothelioma in Australia to the year 2020 are in the order of a total of 10,000 new cases. Compensation claims are testing the attribution in a particular case between occupational asbestos exposure and lung cancer. The cost of the problem necessitates clarifying and standardizing the criteria for a confident diagnosis of asbestos-related disease. The possibility of differences in criteria that determine attribution of asbestos to a disease prompted a consensus meeting of pathologists, epidemiologists, physicians, oncologists, radiologists, and others to define current thinking and to agree on an Australian document based on the scientific evidence for establishing diagnoses and attribution data of asbestos-related diseases in Australia. The participants' findings are reported.}, } @article {pmid15070023, year = {2004}, author = {Stewart, DJ and Edwards, JG and Smythe, WR and Waller, DA and O'Byrne, KJ}, title = {Malignant pleural mesothelioma--an update.}, journal = {International journal of occupational and environmental health}, volume = {10}, number = {1}, pages = {26-39}, doi = {10.1179/oeh.2004.10.1.26}, pmid = {15070023}, issn = {1077-3525}, mesh = {Asbestos/toxicity ; Combined Modality Therapy ; Environmental Exposure/adverse effects ; Environmental Pollutants/toxicity ; Genetic Therapy/methods ; Global Health ; Humans ; Immunotherapy/methods ; Mesothelioma/chemically induced/*pathology/*therapy ; Neoplasm Staging ; Pleural Neoplasms/chemically induced/*pathology/*therapy ; Prognosis ; }, abstract = {Exposure to asbestos is the most frequent, but not exclusive, cause of malignant mesothelioma. Clinical features include dyspnea, cough, nonspecific chest pain, weight loss and night sweats. Diagnosis may be complicated by histologic difficulties. Thoracoscopic techniques are proving beneficial, but no one method of imaging has proven superior, and disease staging is inconsistent. Conventional treatments such as chemotherapy, surgery, and radiotherapy have had variable impacts, although chemotherapy is useful in palliation and can improve both survival and quality of life. There is hope for new antimetabolite agents. The role of radical surgery is yet to be evaluated in a large trial. New radiotherapeutic techniques to improve local control are promising. Multimodality treatments appear to be the most successful for management of potentially resectable disease. It is likely that biological markers will improve accuracy in staging and prognosis. With new treatments based on better understanding of the biology of the disease, there is cautious optimism for the future for patients with malignant pleural mesothelioma.}, } @article {pmid15070022, year = {2004}, author = {Tossavainen, A}, title = {Global use of asbestos and the incidence of mesothelioma.}, journal = {International journal of occupational and environmental health}, volume = {10}, number = {1}, pages = {22-25}, doi = {10.1179/oeh.2004.10.1.22}, pmid = {15070022}, issn = {1077-3525}, mesh = {Asbestos/supply & distribution/*toxicity ; Carcinogens/*toxicity ; Environmental Pollutants/*toxicity ; Global Health ; Humans ; Mesothelioma/*chemically induced/epidemiology ; Occupational Diseases/chemically induced/epidemiology ; Occupational Exposure/adverse effects ; Pleural Neoplasms/*chemically induced/epidemiology ; Registries ; }, abstract = {In Western Europe, Scandinavia, North America, and Australia the manufacture and use of asbestos products peaked in the 1970s. Current incidences of mesothelioma range from 14 to 35 cases/million/year in 11 industrialized countries that had used asbestos 2.0 to 5.5 kg/capita/year about 25 years earlier. A significant linear correlation (r = 0.80, p 0.01) exists between the two variables. Accordingly, about 170 tons of produced and consumed asbestos will cause at least one death from mesothelioma, most often as a consequence of occupational exposure.}, } @article {pmid15064170, year = {2004}, author = {Fonte, R and Gambettino, S and Melazzini, M and Scelsi, M and Zanon, C and Candura, SM}, title = {Asbestos-induced peritoneal mesothelioma in a construction worker.}, journal = {Environmental health perspectives}, volume = {112}, number = {5}, pages = {616-619}, pmid = {15064170}, issn = {0091-6765}, mesh = {Aged ; Asbestos/*toxicity ; Humans ; Immunohistochemistry ; Male ; Mesothelioma/*diagnosis/*etiology/pathology ; Occupational Diseases/*diagnosis/*etiology/pathology ; Peritoneal Neoplasms/*diagnosis/*etiology/pathology ; }, abstract = {Occupational and environmental asbestos exposure continues to represent a public health problem, despite increasingly restrictive laws adopted by most industrialized countries. Peritoneal mesothelioma is a rare and aggressive asbestos-related malignancy. We present the case of a 65-year-old man who developed recurrent ascites after having been exposed to asbestos in the building industry for > 40 years. Liver function and histology were normal. Abdominal computed tomography initially excluded the presence of expansive processes, and no abnormal cells were found in the ascitic fluid. Laparoscopy showed diffuse neoplastic infiltration of the peritoneum. Histopathology of bioptic samples revealed epithelioid neoplastic proliferation with a tubulopapillary pattern, falsely suggesting metastatic adenocarcinomatosis. In consideration of the occupational history, and after further diagnostic procedures had failed to identify the hypothetical primitive tumor, immunostaining of the neoplastic tissue was performed. Results were negative for carcinoembrionary antigen and the epithelial glycoprotein Ber-EP4, whereas results were positive for the mesothelial markers cytokeratins, calretinin, epithelial membrane antigen, and HBME-1, thus leading to the correct diagnosis of peritoneal epithelial mesothelioma. The Italian Workers' Compensation Authority recognized the occupational origin of the disease. Cytoreductive surgery associated with continuous hyperthermic peritoneal perfusion (cisplatin at 42 degrees C, for 1 hr) was performed. The disease relapsed after 4 months and was later complicated by a bowel obstruction requiring palliative ileostomy. The patient died 23 months after diagnosis. This case illustrates the insidious diagnostic problems posed by peritoneal mesothelioma, a tumor which often simulates other malignancies (e.g., metastatic carcinomas) at routine histopathological examination. Occupational history and immunohistochemistry are helpful for the correct diagnosis, which, in turn, is important in relation to prognosis and treatment (adoption of new integrated procedures that seem to promise prolonged survival and increased quality of life), and in relation to medicolegal issues and occupation-related compensation claims following asbestos exposure.}, } @article {pmid19330127, year = {2004}, author = {Shukla, A and Vacek, P and Mossman, BT}, title = {Dose-Response Relationships in Expression of Biomarkers of Cell Proliferation in in vitro Assays and Inhalation Experiments.}, journal = {Nonlinearity in biology, toxicology, medicine}, volume = {2}, number = {2}, pages = {117-128}, pmid = {19330127}, issn = {1540-1421}, abstract = {Asbestos is a group of naturally occurring mineral fibers which are associated in occupational settings with increased risks of malignant mesothelioma (MM), lung cancers, and pulmonary fibrosis (asbestosis). The six recognized types of asbestos fibers (chrysotile, crocidolite, amosite, tremolite, anthophyllite, and actinolite) are different chemically and physically and may have different dose-response relationships in the development of various asbestos-associated diseases. For example, epidemiologic and lung fiber content studies suggest that the pathogenic potential and durability of crocidolite is much greater than chrysotile asbestos in the causation of human MM. We have used isolated mesothelial cells, the target cells of MM, as well as epithelial cells of the lung, the target cells of lung cancers, in vitro to elucidate the dose-response relationships in expression of early response protooncogenes and other genes critical to cell proliferation and malignant transformation in cells exposed to crocidolite and chrysotile asbestos, as well as a number of nonpathogenic fibers and particles. These studies reveal distinct dose-response patterns with different types of asbestos, suggesting a threshold for effects of chrysotile both in in vitro studies and inhalation experiments. The different patterns of gene expression have been confirmed in lungs of rats exposed by inhalation to these types of asbestos. Experiments also suggest no observed adverse effect levels after evaluation of lung injury, inflammation, and fibrosis at lower concentrations of both types of asbestos.}, } @article {pmid15044579, year = {2004}, author = {Hamilton, WT and Round, AP and Sharp, DJ and Peters, TJ}, title = {High incidence of mesothelioma in an English city without heavy industrial use of asbestos.}, journal = {Journal of public health (Oxford, England)}, volume = {26}, number = {1}, pages = {77-78}, doi = {10.1093/pubmed/fdh116}, pmid = {15044579}, issn = {1741-3842}, mesh = {Adult ; Aged ; Asbestos/toxicity ; England/epidemiology ; Female ; Humans ; Incidence ; Industry ; Lung Neoplasms/diagnosis/*epidemiology ; Male ; Mesothelioma/diagnosis/*epidemiology ; Middle Aged ; Occupational Exposure/adverse effects/statistics & numerical data ; Primary Health Care/*statistics & numerical data ; Registries ; }, abstract = {BACKGROUND: Mesothelioma rates are increasing in the industrialized world, related to occupational asbestos exposure. The highest rates have been reported from areas with specific industries such as shipbuilding or mining. Lower rates have been reported from areas without such industries. We studied an area without heavy industry to examine if such a pattern occurred in England.

METHODS: We studied the population of Exeter Primary Care Trust, Devon, United Kingdom, with a population of 131,849. Exeter has no mining, shipbuilding or other heavy industry. All lung cancers and mesotheliomas were identified from the local cancer registry, supplemented by searches at all primary care practices. The cancer diagnoses were checked by inspection of histology or primary care records. Occupational data were extracted from the primary care records.

RESULTS: The searches revealed 291 lung cancers, 283 of which had either histological proof or strong clinical evidence for the diagnosis. Twenty-two (8 per cent) of these were pleural mesotheliomas, 17 of these occurring in men. The incidence rate of mesothelioma in men over 40 years was 12.1 per 100,000 per year (95 per cent confidence intervals 7.0-19.3), one of the highest reported rates in the world.

CONCLUSION: The mesothelioma epidemic will extend to areas without local heavy industrial exposure.}, } @article {pmid15039138, year = {2004}, author = {Kinnula, VL and Torkkeli, T and Kristo, P and Sormunen, R and Soini, Y and Pääkkö, P and Ollikainen, T and Kahlos, K and Hirvonen, A and Knuutila, S}, title = {Ultrastructural and chromosomal studies on manganese superoxide dismutase in malignant mesothelioma.}, journal = {American journal of respiratory cell and molecular biology}, volume = {31}, number = {2}, pages = {147-153}, doi = {10.1165/rcmb.2003-0409OC}, pmid = {15039138}, issn = {1044-1549}, mesh = {Adult ; Aged ; Base Sequence ; DNA Primers ; Female ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Male ; Mesothelioma/*enzymology/ultrastructure ; Microscopy, Electron/methods ; Middle Aged ; Oxidative Stress ; Pleural Neoplasms/*enzymology/ultrastructure ; Promoter Regions, Genetic ; Superoxide Dismutase/*genetics ; }, abstract = {Mesothelioma represents an aggressive tumor type with high resistance to all treatment modalities. Its pathogenesis is strongly associated with exposure to asbestos fibers and probably with free radicals. One of the most important free radical scavenging enzymes, mitochondrial manganese superoxide dismutase (MnSOD), has been shown to be elevated in mesothelioma (K. Kahlos et al., 1998, Am. J. Respir. Cell Mol. Biol. 18:570-580). In the present study, we could detect intense ultrastructural accumulation of MnSOD in the mitochondrial compartment of malignant mesothelioma cells. There was no association between the immunohistochemical reactivity and the most common and functional polymorphic variant of MnSOD, the Ala to Val amino acid change at 9 position (16th amino acid from the beginning of the signal sequence), in the 31 mesothelioma cases investigated. Comparative genomic hybridization and fluorescence in situ hybridization did not reveal any changes in chromosome 6, where the MnSOD gene is located. Sequencing of the MnSOD promoter region in four mesothelioma cell lines showed similar nucleotide variables in the malignant and nonmalignant cells. Therefore, the intense expression of MnSOD in the mitochondria of mesothelioma cells does not appear be associated with any major chromosomal alterations or the polymorphism of MnSOD gene. Association with oxidative/nitrosative stress in mesothelioma using nitrotyrosine immunostaining pointed to a tendency for more intense reactivity in those mesotheliomas with higher MnSOD expression (P = 0.069).}, } @article {pmid15036219, year = {2004}, author = {Treggiari, MM and Weiss, NS}, title = {Occupational asbestos exposure and the incidence of non-Hodgkin lymphoma of the gastrointestinal tract: an ecologic study.}, journal = {Annals of epidemiology}, volume = {14}, number = {3}, pages = {168-171}, doi = {10.1016/S1047-2797(03)00241-2}, pmid = {15036219}, issn = {1047-2797}, mesh = {Aged ; Aged, 80 and over ; Asbestos/*poisoning ; Gastrointestinal Diseases/chemically induced/*epidemiology ; Humans ; Incidence ; Lymphoma, Non-Hodgkin/chemically induced/*epidemiology ; Male ; Mesothelioma/chemically induced/*epidemiology ; Middle Aged ; *Occupational Exposure ; SEER Program ; }, abstract = {PURPOSE: A previous case-control study observed a strong association between occupational exposure to asbestos and the incidence of non-Hodgkin lymphoma of the gastrointestinal tract (GINHL). To test this hypothesis, we sought to determine whether the geographic pattern of the incidence of GINHL in the US has paralleled that of mesothelioma.

METHODS: Using data obtained from the nine US regions participating in the National Cancer Institute's Surveillance, Epidemiology and End Results program, we examined the incidence of malignancies among men ages 50 to 84 years between 1973 and 1984.

RESULTS: The rates of mesothelioma, but not of GINHL, were about two times higher in the areas of Seattle and San Francisco, than in the other regions. Overall, there was no correlation between the rates of mesothelioma and of GIHNL (Pearson correlation coefficient-0.12, p = 0.77).

CONCLUSIONS: This ecologic study finds no support for the hypothesis that occupational asbestos exposure is related to the subsequent incidence of GINHL.}, } @article {pmid15036122, year = {2004}, author = {Burmeister, B and Schwerdtle, T and Poser, I and Hoffmann, E and Hartwig, A and Müller, WU and Rettenmeier, AW and Seemayer, NH and Dopp, E}, title = {Effects of asbestos on initiation of DNA damage, induction of DNA-strand breaks, P53-expression and apoptosis in primary, SV40-transformed and malignant human mesothelial cells.}, journal = {Mutation research}, volume = {558}, number = {1-2}, pages = {81-92}, doi = {10.1016/j.mrgentox.2003.11.003}, pmid = {15036122}, issn = {0027-5107}, mesh = {Asbestos/*toxicity ; Cell Line, Transformed ; Comet Assay ; DNA/*drug effects ; *DNA Damage ; Epithelium/*metabolism/pathology ; Fluorescent Antibody Technique ; Humans ; Simian virus 40/physiology ; Tumor Suppressor Protein p53/*genetics ; }, abstract = {Human mesothelial cells (HMC), the progenitor cells of asbestos-induced mesothelioma, are particularly sensitive to the genotoxic effects of asbestos, although the molecular mechanisms by which asbestos induces injury in HMC are not well known. The high susceptibility of HMC to simian virus 40 (SV40)-mediated transformation is assumed to play a causative role in the pathogenesis of mesothelioma. The aim of this study was to investigate the asbestos-induced DNA damage in cultured HMC and SV40-transformed HMC (MeT-5A) compared with their malignant counterparts, i.e. human mesothelioma cells (MSTO). The time-dependent initiation of DNA-strand breaks as well as the induction of oxidative DNA base modifications were key factors for investigation. HMC, MeT-5A and MSTO cells were exposed to chrysotile and crocidolite asbestos (3 microg/cm2) during different time periods (1-72 h). DNA damage was investigated by use of the Comet assay and alkaline unwinding, the latter in combination with the Fpg protein. The P53 level was analyzed by immunofluorescence, and measurement of apoptosis was conducted by flow cytometry. We found a significant induction of DNA damage in asbestos-treated HMC already after an exposure time of 1.5 h. This effect could not be observed in treated MeT-5A and MSTO cells. Also, a time-dependent significant increase in DNA-strand breaks was observed by alkaline unwinding in asbestos-treated HMC, but not in treated MeT-5A and MSTO cells. In none of the three cell lines we could detect oxidative DNA damage recognized by the Fpg protein (e.g. 8-oxo-guanine), up to 24 h after exposure to asbestos. In contrast to what was found in HMC, P53 was over-expressed in untreated MeT-5A and MSTO. The induction of apoptosis by asbestos fibers was suppressed in MeT-5A and MSTO cells. Crocidolite fibers induced the higher genotoxic effects and chrysotile the more pronounced apoptotic effects. We conclude that asbestos induces DNA damage in HMC already after a very short exposure time in the absence of 8-oxo-guanine formation. The presence of SV40-Tag in MeT-5A and MSTO cells results in an increased expression of P53, but not in additive genotoxic effects after exposure to asbestos. The deregulation of the apoptotic pathway may lead to proliferation of genomically damaged cells and finally to the development of mesothelioma.}, } @article {pmid15031405, year = {2004}, author = {Berry, G and de Klerk, NH and Reid, A and Ambrosini, GL and Fritschi, L and Olsen, NJ and Merler, E and Musk, AW}, title = {Malignant pleural and peritoneal mesotheliomas in former miners and millers of crocidolite at Wittenoom, Western Australia.}, journal = {Occupational and environmental medicine}, volume = {61}, number = {4}, pages = {e14}, pmid = {15031405}, issn = {1470-7926}, mesh = {Adult ; Age of Onset ; Aged ; Asbestos, Crocidolite/*toxicity ; Female ; Humans ; Male ; Mesothelioma/*etiology/mortality ; Middle Aged ; *Mining ; Mortality/trends ; Occupational Diseases/*etiology/mortality ; Occupational Exposure/*adverse effects ; Peritoneal Neoplasms/*etiology/mortality ; Pleural Neoplasms/*etiology/mortality ; Survival Analysis ; Textile Industry ; Western Australia/epidemiology ; }, abstract = {AIMS: To report the number of malignant pleural and peritoneal mesotheliomas that have occurred in former Wittenoom crocidolite workers to the end of 2000, and to compare this with earlier predictions.

METHODS: A group of 6493 men and 415 women who had worked at the former Wittenoom crocidolite mine and mill at some time between 1943 and 1966 have been followed up throughout Australia and Italy to the end of 2000.

RESULTS: The cumulative number of mesotheliomas up to 2000 was 235 in men (202 pleural, 33 peritoneal) and seven (all pleural) in women. There had been 231 deaths with mesothelioma (9% of known deaths).

CONCLUSIONS: The number of deaths in men with mesothelioma between 1987 and 2000 was at the low end of the predictions made earlier based on the number of cases to 1986. If this trend continues, it is predicted that about another 110 deaths with mesothelioma will occur in men by 2020.}, } @article {pmid15031396, year = {2004}, author = {McDonald, JC and Harris, J and Armstrong, B}, title = {Mortality in a cohort of vermiculite miners exposed to fibrous amphibole in Libby, Montana.}, journal = {Occupational and environmental medicine}, volume = {61}, number = {4}, pages = {363-366}, pmid = {15031396}, issn = {1470-7926}, mesh = {Aluminum Silicates/*toxicity ; Asbestos, Amphibole/*toxicity ; Cohort Studies ; Humans ; Lung Neoplasms/etiology/*mortality ; Male ; Mesothelioma/etiology/*mortality ; *Mining ; Montana/epidemiology ; Regression Analysis ; Risk Factors ; }, abstract = {BACKGROUND: Fibrous tremolite is a widespread amphibole asbestiform mineral, airborne fibres of which constitute an environmental hazard in Libby, Montana, northern California, and elsewhere.

AIMS: To determine excess risk from lung cancer, mesothelioma, and all-cause mortality in a cohort of men exposed to tremolite, but no other form of asbestos.

METHODS: Mortality by certified cause and various measures of exposure to tremolite and related amphibole fibres was assessed in a cohort of 406 vermiculite mineworkers in Libby, Montana, employed before 1963 and followed until 1999.

RESULTS: Total deaths were: lung cancer 44 (SMR 2.40), non-malignant respiratory disease (NMRD) 51 (SMR 3.09), all causes 285 (SMR 1.27); included among the total were 12 deaths ascribed to mesothelioma (4.21% of all deaths). Adjusted linear increments in relative risks (per 100 f/ml.y), estimated by Poisson regression, were: lung cancer (0.36, 95% CI 0.03 to 1.20), NMRD (0.38, 95% CI 0.12 to 0.96), and all deaths (0.14, 95% CI 0.05 to 0.26).

CONCLUSIONS: The all-cause linear model would imply a 14% increase in mortality for mine workers exposed occupationally to 100 f/ml.y or about 3.2% for a general population exposed for 50 years to an ambient concentration of 0.1 f/ml. Amphibole fibres, tremolite in particular, are likely to be disproportionately responsible for cancer mortality in persons exposed to commercial chrysotile, but to what extent cannot be readily assessed.}, } @article {pmid15030731, year = {2004}, author = {Martínez, C and Monsó, E and Quero, A}, title = {[Emerging pleuropulmonary diseases associated with asbestos inhalation].}, journal = {Archivos de bronconeumologia}, volume = {40}, number = {4}, pages = {166-177}, doi = {10.1016/s1579-2129(06)60209-7}, pmid = {15030731}, issn = {0300-2896}, mesh = {Air Pollutants/adverse effects ; Air Pollutants, Occupational/adverse effects ; Asbestos/*adverse effects/chemistry/isolation & purification ; Asbestosis/epidemiology ; Bronchoalveolar Lavage Fluid/chemistry ; Carcinogens, Environmental/adverse effects ; Humans ; Lung/chemistry/ultrastructure ; Lung Diseases/epidemiology/*etiology/prevention & control ; Lung Neoplasms/etiology/prevention & control ; Mesothelioma/etiology/prevention & control ; Mineral Fibers/analysis ; Nonheme Iron Proteins/isolation & purification ; Pleural Diseases/epidemiology/*etiology/prevention & control ; Pleural Neoplasms/etiology/prevention & control ; }, } @article {pmid15018030, year = {2004}, author = {Smailyte, G and Kurtinaitis, J and Andersen, A}, title = {Cancer mortality and morbidity among Lithuanian asbestos-cement producing workers.}, journal = {Scandinavian journal of work, environment & health}, volume = {30}, number = {1}, pages = {64-70}, doi = {10.5271/sjweh.766}, pmid = {15018030}, issn = {0355-3140}, mesh = {Adult ; Asbestos, Serpentine/*toxicity ; Cause of Death ; Cohort Studies ; Construction Materials/*adverse effects ; Death Certificates ; Female ; Humans ; Incidence ; Lithuania/epidemiology ; Male ; Middle Aged ; Neoplasms/chemically induced/*epidemiology/mortality ; Occupational Diseases/chemically induced/*epidemiology/mortality ; Occupational Exposure/adverse effects/analysis ; Registries ; Risk Assessment ; Sex Factors ; Time Factors ; }, abstract = {OBJECTIVES: This study investigated the incidence of cancer and cause-specific mortality among workers in the two Lithuanian asbestos-cement factories.

METHODS: The study included 1887 asbestos-cement workers, 1285 men and 602 women, and 37000 person-years. The two factories were active from 1956 (A) and 1963 (B), and the workers were observed from 1978 to 2000. The analysis was based on a comparison between the observed and expected numbers of cancer and causes of death. The observed numbers of cancer were obtained through linkage with the national cancer registry. The date and causes of death were obtained from two different sources. The expected numbers were calculated on the basis of gender- and age-specific incidence and mortality rates in 5-year periods from the whole country. Standardized incidence ratios (SIR) and standardized mortality ratios (SMR) and 95% confidence intervals (95% CI) were calculated. Duration of employment and time since first exposure were used as indicators of exposure.

RESULTS: During the follow-up, 1978-2000. 473 deaths were observed versus 489 expected. There was no excess risk of deaths from nonmalignant respiratory diseases, except for an elevated risk of mortality in relation to the digestive organs other than cancer, 18 observed versus 12.2 expected (95% CI 0.9-2.3). There was no excess risk for any types of cancer, except for colorectal cancer in men, 17 observed cases (SIR 1.6, 95% CI 1.6-2.6) and one case of mesothelioma in a woman.

CONCLUSIONS: This study on asbestos-exposed workers did not show any excess risk of respiratory cancer or deaths of pneumoconiosis.}, } @article {pmid15006974, year = {2004}, author = {Cugell, DW and Kamp, DW}, title = {Asbestos and the pleura: a review.}, journal = {Chest}, volume = {125}, number = {3}, pages = {1103-1117}, doi = {10.1378/chest.125.3.1103}, pmid = {15006974}, issn = {0012-3692}, mesh = {Asbestos/*adverse effects ; Asbestosis/*diagnosis ; Environmental Exposure ; Fibrosis ; Humans ; Lung/diagnostic imaging ; Mesothelioma/diagnosis/etiology/pathology ; Pleura/diagnostic imaging/pathology ; Pleural Diseases/diagnostic imaging/*etiology/pathology ; Pleural Effusion/diagnostic imaging/etiology/pathology ; Pleural Neoplasms/diagnosis/etiology/pathology ; Pulmonary Atelectasis/diagnostic imaging/etiology/pathology ; Radiography ; }, } @article {pmid15006637, year = {2004}, author = {Cardile, V and Renis, M and Scifo, C and Lombardo, L and Gulino, R and Mancari, B and Panico, A}, title = {Behaviour of the new asbestos amphibole fluor-edenite in different lung cell systems.}, journal = {The international journal of biochemistry & cell biology}, volume = {36}, number = {5}, pages = {849-860}, doi = {10.1016/j.biocel.2003.09.007}, pmid = {15006637}, issn = {1357-2725}, mesh = {Animals ; Asbestos, Amphibole/metabolism/*toxicity ; Asbestos, Crocidolite/metabolism/toxicity ; Cell Line ; Cells, Cultured ; Comet Assay ; Cytotoxicity Tests, Immunologic ; DNA/drug effects ; Epithelial Cells/drug effects/metabolism ; Fibroblasts/drug effects/metabolism ; Humans ; Lung/cytology/*drug effects/metabolism ; Macrophages/drug effects/metabolism ; Mice ; Nitric Oxide Synthase/metabolism ; Nitric Oxide Synthase Type II ; Reactive Oxygen Species/metabolism ; Tetrazolium Salts/metabolism ; Thiazoles/metabolism ; }, abstract = {The aim of the present research was to determine whether the recently identified and characterized new fibrous amphibole fluoro-edenite may induce a cytopathic response in cultured cells. The final goal was to gain suggestions on the potentiality of fluoro-edenite to be harmful to human beings. Epidemiological studies, in fact, have shown an excess of developing mesothelioma among residents in Biancavilla, a town in eastern Sicily located in the Etna volcanic area. Therefore, we treated human lung fibroblasts, human lung alveolar epithelial cancer cell line A549 and monocyte-macrophage cell line J774 with fluoro-edenite or crocidolite; the latter used as a highly toxic amphibole asbestos reference. Our results show that fluoro-edenite may induce functional modifications and affects some biochemical parameters in tested cell cultures in a concentration and time dependent manner. However, the observed functional modifications induced by fluoro-edenite are generally less dramatic than those induced by crocidolite and more evident on human lung alveolar epithelial cancer cell line A549 with respect to those obtained on human lung fibroblasts or monocyte-macrophage cell line J774. The sequence of the damage is hypothesised to be as follows: at increasing fluoro-edenite concentrations, and/or treatment times, the increase in reactive oxygen species (ROS) production could trigger significant DNA damage in cell cultures, concomitantly with drop in cell metabolism and increase in lactic dehydrogenase release. In conclusion, according to our data, fluoro-edenite appears as a probable carcinogenic agent, responsible for the high incidence of malignant pleural mesothelioma in Biancavilla.}, } @article {pmid14998741, year = {2004}, author = {LaDou, J}, title = {The asbestos cancer epidemic.}, journal = {Environmental health perspectives}, volume = {112}, number = {3}, pages = {285-290}, pmid = {14998741}, issn = {0091-6765}, mesh = {Asbestos/*poisoning ; Commerce ; *Developing Countries ; *Disease Outbreaks ; Financing, Government ; Humans ; International Cooperation ; Lung Neoplasms/*epidemiology/etiology ; Manufactured Materials ; Mesothelioma/*epidemiology/etiology ; Mining ; *Occupational Exposure ; *Occupational Health ; Public Policy ; Risk Assessment ; Workplace ; *World Health Organization ; }, abstract = {The asbestos cancer epidemic may take as many as 10 million lives before asbestos is banned worldwide and exposures are brought to an end. In many developed countries, in the most affected age groups, mesothelioma may account for 1% of all deaths. In addition to mesotheliomas, 5-7% of all lung cancers can be attributed to occupational exposures to asbestos. The asbestos cancer epidemic would have been largely preventable if the World Health Organization (WHO) and the International Labor Organization (ILO) had responded early and responsibly. The WHO was late in recognizing the epidemic and failed to act decisively after it was well under way. The WHO and the ILO continue to fail to address the problem of asbestos mining, manufacturing, and use and world trade of a known human carcinogen. Part of the problem is that the WHO and the ILO have allowed organizations such as the International Commission on Occupational Health (ICOH) and other asbestos industry advocates to manipulate them and to distort scientific evidence. The global asbestos cancer epidemic is a story of monumental failure to protect the public health.}, } @article {pmid14991330, year = {2004}, author = {Neumann, V and Rütten, A and Scharmach, M and Müller, KM and Fischer, M}, title = {Factors influencing long-term survival in mesothelioma patients--results of the German mesothelioma register.}, journal = {International archives of occupational and environmental health}, volume = {77}, number = {3}, pages = {191-199}, pmid = {14991330}, issn = {0340-0131}, mesh = {Aged ; Asbestos/*toxicity ; Case-Control Studies ; Female ; Germany ; Humans ; Male ; Mesothelioma/*mortality/therapy ; Middle Aged ; Pericardium/*pathology ; Peritoneal Neoplasms/*mortality/therapy ; Pleural Neoplasms/*mortality/therapy ; Registries ; *Survival Analysis ; }, abstract = {Between 1987 and 2000, the German mesothelioma register recorded a total of 4,455 patients with malignant mesotheliomas. Survival times for 498 (11.2%) patients were available; 155 patients (study group, 3.5% of the total group) survived for more than 2 years and 343 patients (control group, 7.7% of the total group) survived for fewer than 24 months. Male patients were over-represented in both groups, with 13% of women in the study and 4.4% in the control group. The proportion of pleural mesotheliomas was more than 90% in both groups, with peritoneal cases comprising 6.5% in the study group and 3.2% in the control group. Histologically, the epithelioid subtype was represented in 58% of the study group, whereas the biphasic subtype predominated (67.6%) in the control group. Only 7% of tumours were of the sarcomatoid subtype. The average age of patients in the study group was 57.4 years, thus lower than in the control group (62.8 years). Lung dust analysis showed an increased pulmonary asbestos burden in 94% of all patients; significant differences between the study and control group were not observed. In the majority of the total group pleural effusions were the first symptoms. Therapeutic data were available in fewer than 40% of all cases. Surgical interventions were performed, partly in combination with radiation and chemotherapy and as alternative treatments. Significant deviations in survival time dependent on therapy applied could not be proved. By multivariate analysis (Cox proportional hazards regression model) favourable prognostic factors for long-term survival were epithelioid tumour subtype, comparatively young age (<60 years), and female gender (P<0.05).}, } @article {pmid14989904, year = {2004}, author = {Li, L and Sun, TD and Zhang, X and Li, XY and Fan, XJ and Kenji, M}, title = {[A meta-analysis of cohort studies on cancer mortality among workers exposure to chrysotile fiber alone].}, journal = {Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine]}, volume = {38}, number = {1}, pages = {39-42}, pmid = {14989904}, issn = {0253-9624}, mesh = {Asbestos/poisoning ; Asbestos, Serpentine/*poisoning ; Cohort Studies ; Humans ; Neoplasms/*etiology/mortality ; Occupational Exposure/*adverse effects ; Respiratory Tract Neoplasms/etiology ; Survival Rate ; }, abstract = {OBJECTIVE: To determine there was excessive risk of malignant tumors or not among workers exposure to chrysotile fiber alone by applying a meta-analysis technique.

METHODS: All data meeting the criteria of cohort studies on cancer mortality among workers exposed only to chrysotile would incorporate into the meta-analysis. The pooled standardized mortality ratios (SMR) and their corresponding 95% confidence intervals (95% CI) for main cancer sites were calculated using two approaches of unweighted ratio and random effects model. The heterogeneity and its sources of the results were examined with a Q-statistic and Z-score test.

RESULTS: 26 chrysotile-exposed alone cohorts were summarized. The significantly elevated meta-SMRs for all deaths (1.28), all cancers (1.26), cancers of respiratory organs (2.24), cancer of lung (2.29) and cancer of stomach (1.27) were observed. The significantly elevated meta-SMRs for lung cancer within occupational strata were observed among textile workers (3.64), asbestos products manufacturers (3.07), miners and millers (2.24), cement products workers (1.22), and for stomach cancer among asbestos products manufacturers (1.48). Meta-SMRs for cancers at other sites were not significant.

CONCLUSION: There were excessive risks of lung cancer and mesothelioma among workers exposure to chrysotile fiber alone, and likely no convincing indication of an etiological association between chrysotile exposure and cancers at other sites.}, } @article {pmid14989034, year = {2003}, author = {Dianzani, I and Gibello, L and Biava, A and Tamiazzo, S and Bertolotti, M and Mirabelli, D and Magnani, C}, title = {[Analysis of potential genetic risk factors for the development of malignant mesothelioma caused by asbestos exposure].}, journal = {Pathologica}, volume = {95}, number = {5}, pages = {298-299}, pmid = {14989034}, issn = {0031-2983}, mesh = {Asbestos/*toxicity ; Humans ; Mesothelioma/*etiology/*genetics ; Pleural Neoplasms/*etiology/*genetics ; Risk Factors ; }, } @article {pmid14970292, year = {2004}, author = {Bartrip, PW}, title = {History of asbestos related disease.}, journal = {Postgraduate medical journal}, volume = {80}, number = {940}, pages = {72-76}, pmid = {14970292}, issn = {0032-5473}, mesh = {Asbestos/adverse effects/*history ; Asbestosis/etiology/history ; Forecasting ; History, 20th Century ; Humans ; Lung Neoplasms/etiology/*history ; Mesothelioma/etiology/*history ; Risk Factors ; }, abstract = {The first medical article on the hazards of asbestos dust appeared in the British Medical Journal in 1924. Following inquiries by Edward Merewether and Charles Price, the British government introduced regulations to control dangerous dust emissions in UK asbestos factories. Until the 1960s these appeared to have addressed the problem effectively. Only then, with the discoveries that mesothelioma was an asbestos related disease and that workers other than those employed in the dustiest parts of asbestos factories were at risk, were the nature and scale of the hazard reassessed. In Britain, America, and elsewhere new and increasingly strict regulations were enacted.}, } @article {pmid14968838, year = {2004}, author = {Maynard, C}, title = {Asbestos problems in Montana and California.}, journal = {Environmental science & technology}, volume = {38}, number = {3}, pages = {46A}, doi = {10.1021/es040353o}, pmid = {14968838}, issn = {0013-936X}, mesh = {Asbestos, Amphibole/*adverse effects ; Costs and Cost Analysis ; *Environmental Exposure ; Environmental Pollution/economics/*prevention & control ; Humans ; Mesothelioma/epidemiology/*etiology ; Montana ; Public Health ; United States ; United States Environmental Protection Agency ; }, } @article {pmid14968837, year = {2004}, author = {Trent, T}, title = {Asbestos problems in Montana and California.}, journal = {Environmental science & technology}, volume = {38}, number = {3}, pages = {46A}, pmid = {14968837}, issn = {0013-936X}, mesh = {Animals ; Asbestos, Amphibole/*adverse effects/*analysis ; California ; Dogs ; *Environmental Exposure ; Humans ; Mesothelioma/epidemiology/*etiology ; Montana ; Respiratory Tract Diseases/epidemiology/etiology ; Risk Assessment ; United States ; United States Environmental Protection Agency ; }, } @article {pmid14870808, year = {2003}, author = {Kabir, Z and Clancy, L}, title = {Mesothelioma trends in the Republic of Ireland: an epidemiologic study in the context of the causal pathway.}, journal = {Irish medical journal}, volume = {96}, number = {10}, pages = {299-302}, pmid = {14870808}, issn = {0332-3102}, mesh = {Causality ; Humans ; Incidence ; Ireland/epidemiology ; Mesothelioma/*epidemiology/mortality/pathology ; Pleural Neoplasms/*epidemiology/mortality/pathology ; Risk Factors ; }, abstract = {This study utilized pleural cancer deaths (n = 125) as a surrogate measure for mesothelioma. The existing mesothelioma incidence data (n = 77) were also analysed. Annual-Percent-Change (APC) in age-adjusted rates (European standard population) was estimated. The pleural cancer mortality rates showed an annual rise of 8.9% (95% CI: 7.1%, 10.8%) from 1979 to 1998 (p < 0.0001), and this was steeper from 1990 onwards, especially among the older cohorts (10.9%). The birth-cohorts of 1925-1935 appear to be suffering the highest risk of pleural cancer deaths. The mesothelioma incidence also showed an annual increase of 14.4% (95% CI: -22.7%, 51.4%) from 1994 to 1998 (p = 0.08). The majority of the mesothelioma cases were involved in asbestos-related trades. Seventy (95% CI: 49,101) cases of pleural cancer deaths are predicted for the years 2007-2008, as opposed to 29 cases observed a decade ago in the years 1997-1998. The current APC (8.9%) is also predicted to rise to 10.5% (95% CI: 7.3%, 15.0%) in 2007-2008. These findings merit close attention for future public-health policies in line with EC directive of banning the indiscriminate use of 'all' forms of asbestos in the Republic of Ireland as early as possible.}, } @article {pmid14870791, year = {2003}, author = {Panetta, A and Geminiani, ML}, title = {Mesothelioma following exposure to asbestos used in sugar refineries: report of two cases and review of the literature.}, journal = {Tumori}, volume = {89}, number = {5}, pages = {573-574}, doi = {10.1177/030089160308900527}, pmid = {14870791}, issn = {0300-8916}, mesh = {Aged ; Asbestos/*adverse effects ; Carbohydrates ; Carcinogens/*adverse effects ; Chemical Industry ; Environmental Exposure/*adverse effects ; Female ; Humans ; Italy ; Male ; Mesothelioma/*chemically induced/drug therapy ; Occupational Diseases/chemically induced ; Occupational Exposure/*adverse effects ; Palliative Care/methods ; Pleural Neoplasms/*chemically induced/drug therapy ; }, abstract = {We report two cases of pleural mesothelioma occurring simultaneously in a sugar refinery worker exposed to asbestos fibers and his wife, who used to wash his working clothes for at least 22 years. A review of the literature is also presented. While demonstrating the carcinogenic risk of asbestos used in sugar refinery plants, our data and those of the literature in no way reflect the real dimension of the risk. Further research will be necessary to assess this risk.}, } @article {pmid14769760, year = {2004}, author = {Ohar, J and Sterling, DA and Bleecker, E and Donohue, J}, title = {Changing patterns in asbestos-induced lung disease.}, journal = {Chest}, volume = {125}, number = {2}, pages = {744-753}, doi = {10.1378/chest.125.2.744}, pmid = {14769760}, issn = {0012-3692}, mesh = {Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Asbestosis/*diagnostic imaging/epidemiology/*pathology ; Biopsy, Needle ; Case-Control Studies ; Cohort Studies ; Female ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Occupational Exposure/*adverse effects ; Probability ; Prognosis ; Regression Analysis ; Respiratory Function Tests ; Risk Assessment ; Severity of Illness Index ; Sex Distribution ; Smoking/*adverse effects ; Spirometry ; Tomography, X-Ray Computed ; }, abstract = {STUDY OBJECTIVES: To determine patterns in asbestos-induced lung diseases found in older, less exposed workers.

DESIGN: Review of a database evaluating lung function, smoking status, form of asbestos-induced lung disease, and radiograph abnormalities.

SETTING: Outpatient clinic.

PARTICIPANTS: A total of 3383 asbestos-exposed workers referred for independent medical evaluation, including control subjects who lacked asbestos-specific radiograph abnormalities (n = 243), subjects with low International Labor Organization (ILO) scores (n = 2,685), high ILO scores (n = 312), bronchogenic cancer (n = 63), and mesothelioma (n = 80). Of these, 3,327 workers have specific smoking status information and 3,312 workers have lung volume measures.

INTERVENTIONS: Chest radiographs were interpreted by a certified B-reader, and abnormalities were quantified according to the ILO scoring system. Spirometry and lung volume measurement were performed. Subjects completed a self-administered questionnaire that was reviewed at the time of examination. Control subjects were screened on two separate occasions at least 10 years apart to exclude subclinical or slowly progressive asbestos-induced lung disease.

MEASUREMENTS AND RESULTS: The mean age of the population was 65.1 +/- 9.9 years, and the latency was 41.4 +/- 10.1 years (+/- SD). Most subjects (41.8%) had normal pulmonary function. Obstruction was the most common pulmonary function abnormality (25.4%), followed by restriction (19.3%) and a mixed pattern (6.0%). Most subjects (79.4%) had low ILO scores. Benign pleural abnormalities were the only findings in 54% of subjects with low ILO score. Subjects with high ILO scores were older, smoked more, and had a longer latency than subjects with low ILO scores and control subjects. Smokers were younger, had a shorter latency, and had paradoxically greater ILO scores than nonsmokers. Subjects with bronchogenic cancer and mesothelioma had longer latencies than control subjects and subjects with benign asbestos-induced lung disease.

CONCLUSIONS: Asbestos-induced lung disease today is characterized by low ILO scores, long latencies, greater disease magnitude in smokers, and a normal or obstructive pattern of pulmonary function abnormality. Spirometric evaluation in the absence of lung volume measurements caused misclassification that resulted in overestimation of the presence of a restrictive pattern of pulmonary function.}, } @article {pmid14768244, year = {2003}, author = {Chiappino, G and Mensi, C and Riboldi, L and Rivolta, G}, title = {[Asbestos risk in the textile industry: final confirmation of data from the Lombardy Mesothelioma Registry].}, journal = {La Medicina del lavoro}, volume = {94}, number = {6}, pages = {521-530}, pmid = {14768244}, issn = {0025-7818}, mesh = {Asbestos/*toxicity ; Humans ; Italy ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; Occupational Exposure/*adverse effects ; Registries ; Respiratory Tract Neoplasms/*etiology ; Risk Factors ; *Textile Industry ; }, abstract = {BACKGROUND: Cases of mesothelioma in non-asbestos textile workers have been frequently reported but the identification of asbestos dispersion sources in the workplaces has never been adequately performed. During 3 years of activity of the Mesothelioma Register for Lombardy, 40 cases (10.8% of all cases) were collected in textile workers engaged in all types of productive activities. The hypothesis that a significant asbestos risk for textile workers appeared not negligible.

OBJECTIVES: The research was aimed at the identification of asbestos dispersion sources in textile factories.

METHODS: Specific information was collected by technicians, maintenance personnel and other experts and direct inspections were carried out in numerous workplaces that had not yet undergone significant changes with respect to the past. Also the industrial machinery utilised in the previous 40-50 years was thoroughly examined.

RESULTS: Epidemological evaluation of the recorded cases showed a widespread distribution in the different phases of textile production. Inspections also showed that a large amount of asbestos had been regularly used applied to the ceilings and also to the walls of factories in order to avoid both condensation of steam and reflection of noise. In addition, asbestos had also been widely used to insulate water and steam pipes. The braking systems of most of the machines also had asbestos gaskets, and on several looms some brakes operated continuously in order to keep the warp in constant tension.

CONCLUSIONS: Our observations confirmed that since production techniques in the textile industry required working in damp and warm conditions with the noise of the rapidly moving machines, asbestos was very often used because of its absorbent and soundproofing qualities and its resistance to friction. We demonstrated that asbestos was thus widely used in the industry and this certainly produced considerable fibre dispersions in the atmosphere of the workplaces. Asbestos risk must therefore be recognised for all those who have worked in the textile industry in the recent past and, as a result, cases of mesothelioma must be considered occupational diseases.}, } @article {pmid14764046, year = {2004}, author = {Van Kesteren, P and Bulten, J and Schijf, C and Boonstra, H and Massuger, L}, title = {Malignant peritoneal mesothelioma in a 76-year-old woman with a history of asbestos fiber ingestion.}, journal = {International journal of gynecological cancer : official journal of the International Gynecological Cancer Society}, volume = {14}, number = {1}, pages = {162-165}, doi = {10.1111/j.1048-891x.2004.14149.x}, pmid = {14764046}, issn = {1048-891X}, mesh = {Aged ; Asbestos/*adverse effects ; Diagnosis, Differential ; Female ; Food Contamination ; Humans ; Mesothelioma/chemically induced/*diagnosis/pathology/surgery ; Peritoneal Neoplasms/chemically induced/*diagnosis/pathology/surgery ; Water Pollutants, Chemical/*adverse effects ; }, abstract = {We report on a woman with malignant mesothelioma of the peritoneum. This is the first report of a subject with this disease who revealed a history of asbestos ingestion by asbestos-contaminated food. She presented with episodes of sweating and fever, ascites, and weight loss. At laparotomy, small tumor deposits were noted on the peritoneum. The omental cake was removed, together with the uterus, ovaries, and tubes which were all macroscopically normal. The diagnosis was established by immunohistochemistry and electron microscopy. Postoperatively, her complaints of fever and sweating disappeared. She refused further chemotherapy. After questioning her for asbestos exposure, she told us that, years ago, she used to prepare vegetables for cooking in rain water collected from a roof made of asbestos.}, } @article {pmid14757710, year = {2003}, author = {Boffetta, P and Nyberg, F}, title = {Contribution of environmental factors to cancer risk.}, journal = {British medical bulletin}, volume = {68}, number = {}, pages = {71-94}, doi = {10.1093/bmp/ldg023}, pmid = {14757710}, issn = {0007-1420}, mesh = {Air Pollution/adverse effects ; Arsenic/toxicity ; Asbestos/toxicity ; Environmental Exposure/adverse effects ; Environmental Pollutants/*toxicity ; Humans ; Neoplasms/*chemically induced ; Radon/toxicity ; Risk Factors ; Tobacco Smoke Pollution/adverse effects ; Water Purification ; Water Supply ; }, abstract = {Environmental carcinogens, in a strict sense, include outdoor and indoor air pollutants, as well as soil and drinking water contaminants. An increased risk of mesothelioma has consistently been detected among individuals experiencing residential exposure to asbestos, whereas results for lung cancer are less consistent. At least 14 good-quality studies have investigated lung cancer risk from outdoor air pollution based on measurement of specific agents. Their results tend to show an increased risk in the categories at highest exposure, with relative risks in the range 1.5-2.0, which is not attributable to confounders. Results for other cancers are sparse. A causal association has been established between exposure to environmental tobacco smoke and lung cancer, with a relative risk in the order of 1.2. Radon is another carcinogen present in indoor air which may be responsible for 1% of all lung cancers. In several Asian populations, an increased risk of lung cancer is present in women from indoor pollution from cooking and heating. There is strong evidence of an increased risk of bladder, skin and lung cancers following consumption of water with high arsenic contamination; results for other drinking water contaminants, including chlorination by-products, are inconclusive. A precise quantification of the burden of human cancer attributable to environmental exposure is problematic. However, despite the relatively small relative risks of cancer following exposure to environmental carcinogens, the number of cases that might be caused, assuming a causal relationship, is relatively large, as a result of the high prevalence of exposure.}, } @article {pmid14751871, year = {2004}, author = {Treasure, T and Waller, D and Swift, S and Peto, J}, title = {Radical surgery for mesothelioma.}, journal = {BMJ (Clinical research ed.)}, volume = {328}, number = {7434}, pages = {237-238}, pmid = {14751871}, issn = {1756-1833}, mesh = {Asbestos/*adverse effects ; Humans ; Male ; Mesothelioma/mortality/*surgery ; Middle Aged ; Occupational Exposure/adverse effects ; Pleural Neoplasms/mortality/*surgery ; }, } @article {pmid14751636, year = {2004}, author = {Winfree, CJ and Mack, WJ and Sisti, MB}, title = {Solitary cerebellar metastasis of malignant pleural mesothelioma: case report.}, journal = {Surgical neurology}, volume = {61}, number = {2}, pages = {174-8; discussion 178-9}, doi = {10.1016/s0090-3019(03)00448-8}, pmid = {14751636}, issn = {0090-3019}, mesh = {Aged ; Cerebellar Neoplasms/diagnosis/*secondary/surgery ; Female ; Humans ; Magnetic Resonance Imaging ; Mesothelioma/diagnosis/*secondary/surgery ; Neurosurgical Procedures/methods ; Pleural Effusion, Malignant/*diagnosis ; Pleural Neoplasms/*pathology/surgery ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma is an uncommon malignancy that rarely metastasizes to the central nervous system and even less frequently occurs as a solitary lesion.

CASE DESCRIPTION: We present a 71-year-old white female, nonsmoker, with no occupational exposure to asbestos. She presented with a 15-lb. weight loss over several months and persistent right subscapular pain radiating to her anterior chest. Imaging studies revealed a pleural mass, and biopsy confirmed fibrous type malignant pleural mesothelioma. During a metastatic workup, computed tomography (CT) and magnetic resonance imaging (MRI) of the head demonstrated a 1 cm subcortical, contrast-enhancing lesion without surrounding edema in the right posterior cerebellum. Surgical resection of the solitary cerebellar mass revealed fibrous-type metastatic malignant mesothelioma. Postoperatively, the patient received a combined chemotherapy regimen of Adriamycin and Cisplatin and underwent whole brain radiation therapy.

CONCLUSIONS: We report the first resection of a solitary cerebellar metastasis of malignant pleural mesothelioma. We also review past cases of intracranial metastasis of this malignancy, its histologic subtypes, outcome, and recent treatment modalities.}, } @article {pmid14739381, year = {2004}, author = {Gun, RT and Pratt, NL and Griffith, EC and Adams, GG and Bisby, JA and Robinson, KL}, title = {Update of a prospective study of mortality and cancer incidence in the Australian petroleum industry.}, journal = {Occupational and environmental medicine}, volume = {61}, number = {2}, pages = {150-156}, pmid = {14739381}, issn = {1470-7926}, mesh = {Australia/epidemiology ; *Cause of Death ; Confidence Intervals ; *Extraction and Processing Industry ; Female ; Humans ; Incidence ; Male ; Mesothelioma/epidemiology/etiology ; Neoplasms/*epidemiology/etiology/mortality ; Occupational Diseases/*epidemiology/etiology/mortality ; *Petroleum ; Prospective Studies ; Urinary Bladder Neoplasms/epidemiology/etiology ; }, abstract = {AIMS: To update the analysis of the cohort mortality and cancer incidence study of employees in the Australian petroleum industry.

METHODS: Employees from 1981 to 1996 were traced through the Australian National Death Index and the National Cancer Statistics Clearing House. Cause specific mortality and cancer incidence were compared with those of the Australian population by means of standardised mortality ratios (SMRs) and standardised incidence ratios (SIRs). Associations between increased incidence of specific cancers and employment in the petroleum industry were tested by trends according to period of first employment, duration of employment, latency, and hydrocarbon exposure, adjusting for personal smoking history where appropriate. Total follow up time was 176 598 person-years for males and 10 253 person-years for females.

RESULTS: A total of 692 of the 15 957 male subjects, and 16 of the 1206 female subjects had died by the cut off date, 31 December 1996. In males, the all-cause SMR and the SMRs for all major disease categories were significantly below unity. There was a non-significant increase of the all-cancer SIR (1.04, 95% CI 0.97 to 1.11). There was a significant increase of the incidence of melanoma (SIR 1.54, 95% CI 1.30 to 1.81), bladder cancer (SIR 1.37, 95% CI 1.00 to 1.83), and prostate cancer (SIR 1.19, 95% CI 1.00 to 1.40), and a marginally significant excess of pleural mesothelioma (SIR 1.80, 95% CI 0.90 to 3.22), leukaemia (SIR 1.39, 95%CI 0.91 to 2.02), and multiple myeloma (SIR 1.72, 95% CI 0.96 to 2.84).

CONCLUSIONS: Most cases of mesothelioma are probably related to past exposure to asbestos in refineries. The melanoma excess may be the result of early diagnosis. The excess bladder cancer has not been observed previously in this industry and is not readily explained. The divergence between cancer incidence and cancer mortality suggests that the "healthy worker effect" may be related to early reporting of curable cancers, leading to increased likelihood of cure and prolonged mean survival time.}, } @article {pmid14735839, year = {2003}, author = {Bilancia, M and Cavone, D and Pollice, A and Musti, M}, title = {[Assessment of risk of mesothelioma: the case of an asbestos-cement production plant in the city of Bari].}, journal = {Epidemiologia e prevenzione}, volume = {27}, number = {5}, pages = {277-284}, pmid = {14735839}, issn = {1120-9763}, mesh = {Asbestos/*adverse effects ; Construction Materials/*adverse effects ; Environmental Exposure/*adverse effects ; Female ; Humans ; Italy ; Lung Neoplasms/*epidemiology/*etiology ; Male ; Mesothelioma/*epidemiology/*etiology ; Occupational Diseases/*epidemiology/*etiology ; Occupational Exposure/adverse effects ; Risk Assessment ; Urban Population ; }, abstract = {OBJECTIVE: In this paper, by means of explorative methods based on geographical analysis, the relationship between the presence of an asbestos-cement factory in the urban area of Bari and malignant mesothelioma cases, occurring between 1980 and 2001 among residents, is analysed.

METHODS: The data source of the 64 cases studied is the national register of mesotheliomas (Renam), the Apulia regional operating centre (Cor-Puglia). Data are analysed by the use of the S + SpatialStats software.

RESULTS AND DISCUSSION: Both individual data analysis and explorative geographic analysis point out an increased risk of disease among people living near the asbestos-cement factory: within an area centred on the location of plants and having a radius of about 1 Km, the estimated risk is 2.38 times above the normal level. Further analytical studies are required.}, } @article {pmid14732480, year = {2004}, author = {Mohr, S and Keith, G and Galateau-Salle, F and Icard, P and Rihn, BH}, title = {Cell protection, resistance and invasiveness of two malignant mesotheliomas as assessed by 10K-microarray.}, journal = {Biochimica et biophysica acta}, volume = {1688}, number = {1}, pages = {43-60}, doi = {10.1016/j.bbadis.2003.10.007}, pmid = {14732480}, issn = {0006-3002}, mesh = {Biomarkers, Tumor/genetics ; Cell Line, Tumor ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Mesothelioma/etiology/genetics/*pathology ; Multigene Family ; Pleural Neoplasms/etiology/genetics/*pathology ; Protein Array Analysis ; RNA, Messenger/analysis ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive serosal tumor, strongly associated with former exposure to asbestos fibers and for which there is currently no effective treatment available. In human, MPM is characterized by a high local invasiveness, poor prognosis and therapeutic outcomes. In order to assess molecular changes that specify this phenotype, we performed a global gene expression profiling of human MPM. Using a 10,000-element microarray, we analyzed mRNA relative gene expression levels by comparing a mesothelioma cell line to either a pleural cell line or tumor specimens. To analyze these gene expression data, we used various bioinformatics softwares. Hierarchical clustering methods were used to group genes and samples with similar expression in an unsupervised mode. Genes of known function were further sorted by enzyme, function and pathway clusters using a supervised software (IncyteGenomics). Taken together, these data defined a molecular fingerprint of human MPM with more than 700 up- or down-regulated genes related to several traits of the malignant phenotype, specially associated with MPM invasiveness, protection and resistance to anticancer defenses. This portrait is meaningful in disease classification and management, and relevant in finding new specific markers of MPM. These molecular markers should improve the accuracy of mesothelioma diagnosis, prognosis and therapy.}, } @article {pmid14725101, year = {2003}, author = {Rosenthal, R and Langer, I and Dalquen, P and Marti, WR and Oertli, D}, title = {Peritoneal mesothelioma after environmental asbestos exposure.}, journal = {Swiss surgery = Schweizer Chirurgie = Chirurgie suisse = Chirurgia svizzera}, volume = {9}, number = {6}, pages = {311-314}, doi = {10.1024/1023-9332.9.6.311}, pmid = {14725101}, issn = {1023-9332}, mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Asbestos/*adverse effects ; Asbestosis/diagnostic imaging/*drug therapy ; Cisplatin/administration & dosage ; Disease Progression ; Environmental Pollutants/*adverse effects ; Follow-Up Studies ; Humans ; Injections, Intraperitoneal ; Laparoscopy ; Male ; Mesothelioma/diagnostic imaging/*drug therapy ; Palliative Care ; Peritoneal Neoplasms/diagnostic imaging/*drug therapy ; Switzerland ; *Tomography, X-Ray Computed ; Turkey/ethnology ; }, abstract = {Mesothelioma are primary malignant neoplasms of the serous membranes. They usually involve the pleura and rarely the pericardium, the peritoneum and the tunica vaginalis testis. About 90% are associated with exposure to asbestos. The exposure is generally occupational, an environmental inhalation of asbestos and asbestiform fibers in areas in Turkey has been observed and presents a major health problem. This report of a patient from Anatolia with peritoneal mesothelioma after environmental exposure outlines the importance of considering this pathology in the differential diagnosis of a Turkish patient presenting with ascites.}, } @article {pmid14724482, year = {2004}, author = {Ulvestad, B and Kjaerheim, K and Martinsen, JI and Mowe, G and Andersen, A}, title = {Cancer incidence among members of the Norwegian trade union of insulation workers.}, journal = {Journal of occupational and environmental medicine}, volume = {46}, number = {1}, pages = {84-89}, doi = {10.1097/01.jom.0000105981.46987.42}, pmid = {14724482}, issn = {1076-2752}, mesh = {Asbestos/*adverse effects ; Cohort Studies ; Humans ; Incidence ; Labor Unions ; Lung Neoplasms/epidemiology/*etiology ; Male ; Mesothelioma/epidemiology/*etiology ; Norway/epidemiology ; Occupational Diseases/epidemiology/*etiology ; }, abstract = {Insulation work has been described as an occupation with high exposure to asbestos. A cohort of members of the Norwegian Trade Union of Insulation Workers (n = 1116), hired between 1930 and 1975, was established. During 2002, the cohort was linked to the Cancer Registry of Norway. The standardized incidence ratio (SIR) of pleural mesothelioma was 12.9 (95% confidence interval [CI] = 6.0-24.6). Two cases with peritoneal mesotheliomas were found (SIR, 14.8; 95% CI = 1.8-53.4). The SIR of lung cancer was 3.0 (95% CI = 2.3-3.8). Four cases of lung cancer were observed among cork workers without any exposure to asbestos, but to cork dust and tar smoke (SIR, 5.3; 95% CI = 1.5-13.6). Our study showed a high risk of mesothelioma and an elevated risk of lung cancer among members of the Trade Union of Insulation Workers.}, } @article {pmid14718210, year = {2004}, author = {Price, B and Ware, A}, title = {Mesothelioma trends in the United States: an update based on Surveillance, Epidemiology, and End Results Program data for 1973 through 2003.}, journal = {American journal of epidemiology}, volume = {159}, number = {2}, pages = {107-112}, doi = {10.1093/aje/kwh025}, pmid = {14718210}, issn = {0002-9262}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Child ; Child, Preschool ; Cohort Studies ; Female ; Humans ; Incidence ; Infant ; Infant, Newborn ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Risk Factors ; SEER Program/*statistics & numerical data ; Sex Factors ; United States/epidemiology ; }, abstract = {Using 1973-2000 mesothelioma incidence data released by the Surveillance, Epidemiology, and End Results Program in April 2003, the authors estimated the parameters of a birth-cohort and age model to determine whether previously reported patterns of mesothelioma in the United States have changed. Compared with analyses based on data through 1992, a slower decline was found in male cases immediately after a peak in 2000-2004, but no other notable changes in the time pattern were detected. Analysis confirmed that the annual number of male mesothelioma cases, which increased steeply from the 1970s through the mid-1990s, has leveled off in terms of both the age-adjusted rate and the absolute numbers of cases. After a peak of approximately 2,000 cases, a return to background levels is expected by 2055. The total projected number of male mesothelioma cases in 2003-2054 is approximately 71,000. The maximum lifetime risk for males, which occurs for the 1925-1929 birth cohort, is 1.8 x 10(-3). The age-adjusted rate for females is constant, as are the female lifetime mesothelioma risk across birth cohorts (3.6 x 10(-4)) and the annual risk (3.9 x 10(-6)). The time pattern of cases for females supports the existence of a threshold exposure for mesothelioma and a quantifiable background rate.}, } @article {pmid14702560, year = {2003}, author = {Lanzetta, E}, title = {Research needed for mesothelioma. Financial compensation after death is no panacea.}, journal = {The American journal of nursing}, volume = {103}, number = {12}, pages = {11}, doi = {10.1097/00000446-200312000-00002}, pmid = {14702560}, issn = {0002-936X}, mesh = {Asbestos/adverse effects ; Carcinogens/adverse effects ; Compensation and Redress/*legislation & jurisprudence ; Humans ; Lung Neoplasms/etiology/*therapy ; Mesothelioma/etiology/*therapy ; Needs Assessment/economics/*legislation & jurisprudence ; Research/economics/*legislation & jurisprudence ; United States ; }, } @article {pmid19227586, year = {2004}, author = {Davies, JC}, title = {Early South African insights into the risks of exposure to asbestos dust: Drs Simson, Strachan and Slade.}, journal = {Adler Museum bulletin}, volume = {30}, number = {2}, pages = {17-23}, pmid = {19227586}, issn = {0258-2058}, mesh = {*Asbestos/economics/history ; Asbestos, Amosite/economics/history ; Asbestos, Crocidolite/economics/history ; History, 19th Century ; History, 20th Century ; *Mesothelioma/economics/ethnology/history/psychology ; Mining/economics/education/history/legislation & jurisprudence ; *Occupational Medicine/economics/education/history/legislation & jurisprudence ; Pathology/economics/education/history/legislation & jurisprudence ; *Physicians/economics/history/legislation & jurisprudence/psychology ; *Public Health/economics/education/history/legislation & jurisprudence ; Research/economics/education/history/legislation & jurisprudence ; Research Personnel/economics/education/history/legislation & jurisprudence/psychology ; *Respiratory Tract Diseases/economics/ethnology/history/psychology ; *Silicosis/economics/ethnology/history/psychology ; South Africa/ethnology ; Workplace/economics/history/legislation & jurisprudence/psychology ; }, } @article {pmid14700305, year = {2003}, author = {Renner, R}, title = {Asbestos investigation under way.}, journal = {Environmental science & technology}, volume = {37}, number = {23}, pages = {426A-428A}, doi = {10.1021/es0326423}, pmid = {14700305}, issn = {0013-936X}, mesh = {Amphibians ; Animals ; Asbestos, Amphibole/*adverse effects/*analysis ; California ; *Environmental Exposure ; Environmental Monitoring ; Epidemiological Monitoring ; Humans ; Mesothelioma/epidemiology/*etiology ; Mining ; Public Health ; Respiratory Tract Diseases/epidemiology/etiology ; Risk Assessment ; Toxicity Tests ; }, } @article {pmid14694617, year = {2002}, author = {Wang, J and Luo, S and Zhang, Y and Wen, Q and Cai, S and Wu, D and Sun, D}, title = {[Risk factors for malignant pleural mesothelioma in crocidolite contaminated area].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {20}, number = {2}, pages = {87-89}, pmid = {14694617}, issn = {1001-9391}, mesh = {Asbestos, Crocidolite/*adverse effects ; Case-Control Studies ; Environmental Exposure ; Family ; Humans ; Life Style ; Mesothelioma/*etiology/genetics ; Middle Aged ; Pleural Neoplasms/*etiology/genetics ; Risk Factors ; }, abstract = {OBJECTIVE: To explore the risk factors for mesothelioma so as to provide epidemiological evidences for prevention of this disease and for further study of its pathogenesis.

METHODS: A 1:1 paired case-control study was carried out in which asbestos exposure, life style and histories of cancer in first-degree relatives of 23 patients who had mesothelioma were compared with those of controls.

RESULTS: The mean age of patients was 57.96 years with a latency period of 52 years. There were no significant differences in mean exposure age, mean exposure periods, and smoking, drinking habits between patients and controls. The mean cumulative exposure of patients was 37.2 x 10(5) f, which was significantly higher than that of controls (32.3 x 10(5) f, P = 0.005). The odds ratio increased with the cumulative exposure. The percentage of cancer in first-degree relative of patients (26.1%) was significantly higher than that of controls [(4.4%, P < 0.05), OR = 7.75 (95% CI: 0.85-71.43)].

CONCLUSION: There may be a dose-response relationship between mesothelioma and asbestos exposure. A family history of cancer may be a risk factor for mesothelioma, or may indicate an increased susceptibility to mesothelioma under the same level of asbestos exposure.}, } @article {pmid14691969, year = {2004}, author = {Nesti, M and Marinaccio, A and Chellini, E}, title = {Malignant mesothelioma in Italy, 1997.}, journal = {American journal of industrial medicine}, volume = {45}, number = {1}, pages = {55-62}, doi = {10.1002/ajim.10313}, pmid = {14691969}, issn = {0271-3586}, mesh = {Adolescent ; Adult ; Age Distribution ; Aged ; Asbestos/*toxicity ; Child ; Child, Preschool ; Environmental Exposure/*adverse effects ; Female ; Humans ; Incidence ; Infant ; Infant, Newborn ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology/*etiology ; Middle Aged ; Occupational Exposure/*adverse effects ; Occupations/classification ; Peritoneal Neoplasms/*epidemiology/*etiology ; Pleural Neoplasms/*epidemiology/*etiology ; *Population Surveillance ; Registries ; Sex Distribution ; }, abstract = {BACKGROUND: The Italian National Mesothelioma Register (ReNaM) was set up at the Istituto Superiore Prevenzione e Sicurezza Lavoro (ISPESL), in Rome, in accordance with Art. 36 of Italian Legislative Decree No. 277 [1991].

METHODS: Five Italian regions, Piedmont, Liguria, Emilia-Romagna, Tuscany, and Apulia, agreed to record mesothelioma cases according to guidelines established by ISPESL, to define exposure to asbestos and transmit the data systematically to ISPESL.

RESULTS: Four hundred and twenty-nine mesothelioma cases, diagnosed in 1997, are recorded. The standardized annual incidence rate for definite pleural mesothelioma is 1.51 per 100,000 inhabitants (2.26 for males and 0.79 for females). Exposure was defined for 198 mesotheliomas with a histological diagnosis: 125 (63%) refer to occupational exposure, 10 (5%) to environmental exposure, and 5 (2.5%) to household exposure.

CONCLUSIONS: Despite the ReNaM's work, many limitations still have to be overcome. Clear-cut information on asbestos exposure is available for a limited number of cases; and differing regional procedures in collecting and evaluating mesotheloma cases exist. At this stage the identification and evaluation of a large number of cases of mesothelioma is a worthwhile result. This epidemiological surveillance, currently being extended to other regions, will enable us to better assess the impact and diffusion of this disease in future, and to monitor more closely the effects of ceasing asbestos use in 1992, and the efficacy of preventive measures since mid '70s. Am. J. Ind. Med. 45:55-62, 2004.}, } @article {pmid14681081, year = {2004}, author = {Paustenbach, DJ and Finley, BL and Lu, ET and Brorby, GP and Sheehan, PJ}, title = {Environmental and occupational health hazards associated with the presence of asbestos in brake linings and pads (1900 to present): a "state-of-the-art" review.}, journal = {Journal of toxicology and environmental health. Part B, Critical reviews}, volume = {7}, number = {1}, pages = {25-80}, doi = {10.1080/10937400490231494}, pmid = {14681081}, issn = {1093-7404}, mesh = {Air Pollutants, Occupational/*toxicity ; Asbestos/*toxicity ; Asbestosis/*epidemiology ; *Automobiles ; Environmental Exposure/adverse effects ; Humans ; Manufactured Materials ; Occupational Exposure/adverse effects ; }, abstract = {Throughout the history of automobile development, chrysotile asbestos has been an essential component of vehicle brake linings and pads. Acceptable alternatives were not fully developed until the 1980s, and these were installed in vehicles produced over the past decade. This article presents a "state-of-the-art" analysis of what was known over time about the potential environmental and occupational health hazards associated with the presence of chrysotile asbestos in brake linings and pads. As part of this analysis, the evolution of automobile brakes and brake friction materials, beginning with the early 1900s, is described. Initial concerns regarding exposures to asbestos among workers involved in the manufacture of friction products were raised as early as 1930. Between 1930 and 1959, eight studies were conducted for which friction product manufacturing workers were part of the population assessed. These studies provided evidence of asbestosis among highly exposed workers, but provided little information on the magnitude of exposure. The U.S. Public Health Service proposed the first occupational guideline for asbestos exposure in 1938. The causal relationship between asbestos exposure and lung cancer was confirmed in 1955 in asbestos textile workers in the United Kingdom, and later, in 1960, in South Africa, mesothelioma was attributed to asbestos exposure to even relatively low airborne concentrations of crocidolite. Between 1960 and 1974, five epidemiology studies of friction product manufacturing workers were conducted. During this same time period, the initial studies of brake lining wear (dust or debris) emissions were conducted showing that automobile braking was not a substantial contributor of asbestos fibers greater than 5 microm in length to ambient air. The first exposure surveys, as well as preliminary health effects studies, for brake mechanics were also conducted during this period. In 1971, the Occupational Safety and Health Administration promulgated the first national standards for workplace exposure to asbestos. During the post-1974 time period, most of the information on exposure of brake mechanics to airborne asbestos during brake repair was gathered, primarily from a series of sampling surveys conducted by the National Institute of Occupational Safety and Health in the United States. These surveys indicated that the time-weighted average asbestos}, } @article {pmid14674744, year = {2003}, author = {Montanaro, F and Bray, F and Gennaro, V and Merler, E and Tyczynski, JE and Parkin, DM and Strnad, M and Jechov'a, M and Storm, HH and Aareleid, T and Hakulinen, T and Velten, M and Lef'evre, H and Danzon, A and Buemi, A and Daur'es, JP and Ménégoz, F and Raverdy, N and Sauvage, M and Ziegler, H and Comber, H and Paci, E and Vercelli, M and De Lisi, V and Tumino, R and Zanetti, R and Berrino, F and Stanta, G and Langmark, F and Rachtan, J and Mezyk, R and Blaszczyk, J and Ivan, P and Primic-Zakelj, M and Martínez, AC and Izarzugaza, I and Borràs, J and Garcia, CM and Garau, I and Sánchez, NC and Aicua, A and Barlow, L and Torhorst, J and Bouchardy, C and Levi, F and Fisch, T and Probst, N and Visser, O and Quinn, M and Gavin, A and Brewster, D and Mikov, M and , }, title = {Pleural mesothelioma incidence in Europe: evidence of some deceleration in the increasing trends.}, journal = {Cancer causes & control : CCC}, volume = {14}, number = {8}, pages = {791-803}, doi = {10.1023/a:1026300619747}, pmid = {14674744}, issn = {0957-5243}, mesh = {Asbestos ; Environmental Exposure/adverse effects ; Europe/epidemiology ; Forecasting ; Humans ; Incidence ; Linear Models ; Mesothelioma/*epidemiology/etiology ; Occupational Exposure/adverse effects ; Pleural Neoplasms/*epidemiology/etiology ; Risk Factors ; }, abstract = {OBJECTIVE: To summarize the geographical and temporal variations in incidence of pleural mesothelioma in Europe, using the extensive data available from European general cancer registries, and consider these in light of recent trends in asbestos extraction, use and import in European countries.

MATERIAL AND METHODS: The data were extracted from the European Cancer Incidence and Mortality database (EUROCIM). The inclusion criteria was acceptance in Volume VII of Cancer Incidence in Five Continents. Truncated age-standardized rates per 100,000 for the ages 40-74 were used to summarise recent geographical variations. Standardized rate ratios and 95% confidence intervals for the periods 1986-1990 and 1991-1995 were compared to assess geographical variations in risk. To investigate changes in the magnitude of most recent trends, regression models fitted to the latest available 10-year period (1988-1997) were compared with trends in the previous decade. Fitted rates in younger (40-64) and older adults (65-74) in the most recent period were also compared.

RESULTS: There was a great deal of geographical variation in the risk of mesothelioma, annual rates ranging from around 8 per 100,000 in Scotland, England and The Netherlands, to lower than 1 per 100,000 in Spain (0.96), Estonia (0.85), Poland (0.85) and Yugoslavia, Vojvodina (0.56) among men. The rank of the rates for women was similar to that observed for men, although rates were considerably lower. Between 1978 and 1987, rates in men significantly increased in all countries (excepting Denmark). In the following 10 years, there was a deceleration in trend, and a significant increase was detectable only in England and France. In addition, the magnitude of recent trends in younger men was generally lower than those estimated for older men, in both national and regional cancer registry settings.

CONCLUSIONS: While mesothelioma incidence rates are still rising in Europe, a deceleration has started in some countries. A decrease may begin in the next few years in certain European populations considering the deceleration of observed trends in mesothelioma and asbestos exposure, as well as the recent ban on its use.}, } @article {pmid14667274, year = {2003}, author = {Gazdar, AF and Carbone, M}, title = {Molecular pathogenesis of malignant mesothelioma and its relationship to simian virus 40.}, journal = {Clinical lung cancer}, volume = {5}, number = {3}, pages = {177-181}, doi = {10.3816/CLC.2003.n.031}, pmid = {14667274}, issn = {1525-7304}, mesh = {Asbestos/adverse effects ; Europe/epidemiology ; Humans ; Incidence ; Lung Neoplasms/*etiology/virology ; Mesothelioma/*etiology/virology ; Pleural Effusion, Malignant/etiology/virology ; *Simian virus 40 ; Tumor Virus Infections/etiology/virology ; United States/epidemiology ; }, abstract = {Malignant mesothelioma is a relatively rare tumor, but the incidence of the disease appears to be increasing. Unique molecular changes are associated with the disease that distinguish it from lung cancers. Smoking is not an etiologic factor; the major causative agent is asbestos exposure, usually many years or decades before the development of the tumor. Recently, a simian virus, SV40, has been associated with malignant mesotheliomas and is a probable cofactor in tumor development. The molecular changes caused by each of these major etiologic factors and their interrelationships are the focus of this review.}, } @article {pmid14664497, year = {2003}, author = {Hansen, ES}, title = {Lung cancer in MMVF workers--viewpoints on a null-result study.}, journal = {International journal of occupational and environmental health}, volume = {9}, number = {4}, pages = {397-398}, doi = {10.1179/oeh.2003.9.4.397}, pmid = {14664497}, issn = {1077-3525}, mesh = {Asbestos/*toxicity ; Bias ; Case-Control Studies ; Europe ; Humans ; International Agencies ; Lung Neoplasms/*chemically induced ; Mesothelioma/chemically induced ; Mineral Fibers/*toxicity ; Occupational Exposure/*adverse effects ; Reproducibility of Results ; Research Design ; Time Factors ; }, } @article {pmid14655903, year = {2003}, author = {Comba, P and Gianfagna, A and Paoletti, L}, title = {Pleural mesothelioma cases in Biancavilla are related to a new fluoro-edenite fibrous amphibole.}, journal = {Archives of environmental health}, volume = {58}, number = {4}, pages = {229-232}, doi = {10.3200/AEOH.58.4.229-232}, pmid = {14655903}, issn = {0003-9896}, mesh = {Air Pollutants, Occupational/*adverse effects ; Asbestos, Amphibole/*adverse effects ; Humans ; Italy/epidemiology ; Mesothelioma/*epidemiology/etiology/mortality/prevention & control ; Mineral Fibers/*adverse effects ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*epidemiology/etiology/mortality/prevention & control ; }, abstract = {A cluster of deaths from pleural mesothelioma was previously reported for Biancavilla, Italy, a city in eastern Sicily. An environmental survey suggested that the stone quarries located southeast of the city might be a source of asbestos exposure. The materials extracted from the quarries, used widely in the local building industry, contain large quantities of a fibrous amphibole that was initially referred to as an anomalous intermediate phase of sodium- and fluorine-rich tremolite-actinolite. A subsequent crystal chemistry investigation identified the mineral as fluoro-edenite, a new end-member of the edenite --> fluoro-edenite series. The material is very similar in morphology and composition to the minerals of the tremolite-actinolite series. To the authors' knowledge, fluoro-edenite becomes the 3rd mineral fiber (along with erionite and winchite), not yet classified as asbestos, with a demonstrable mesotheliomatogenous action in humans.}, } @article {pmid14644341, year = {2003}, author = {Puntoni, R and Filiberti, R and Cerrano, PG and Neri, M and Andreatta, R and Bonassi, S}, title = {Implementation of a molecular epidemiology approach to human pleural malignant mesothelioma.}, journal = {Mutation research}, volume = {544}, number = {2-3}, pages = {385-396}, doi = {10.1016/j.mrrev.2003.06.012}, pmid = {14644341}, issn = {0027-5107}, mesh = {Asbestos/toxicity ; DNA Repair/genetics ; Genetic Markers ; Humans ; Lung Neoplasms/chemically induced/*epidemiology/*genetics ; Mesothelioma/chemically induced/*epidemiology/*genetics ; Molecular Epidemiology/methods ; Pleural Neoplasms/chemically induced/epidemiology/genetics ; Polymorphism, Genetic ; }, abstract = {The carcinogenic effect of asbestos has been reported in the literature since 40 years, and early studies describing the epidemic occurrence of malignant mesothelioma (MM) in asbestos workers, have become a paradigm of occupational cancer research. Research on MM was abandoned for many years since MM was considered as an asbestos-related disease, interesting only from a perspective of disease control and preventive policies. The introduction of new biological endpoints in the epidemiological studies has boosted research in the field, providing new tools for the study of emerging priority in cancer research and in public health. This approach, known as molecular epidemiology has a great potential in the study of MM, contributing to the understanding of susceptibility factors, to the evaluation of cancer risk in people occupationally or environmentally exposed to carcinogens, and to the enhancement of diagnosis and therapy. A comprehensive approach based on the use of banks of biological samples is presented and its advantages discussed here. The application of innovative endpoints, such as oncoproteins in biologic fluids, genetic polimorphisms, or gene function is discussed, and relevant literature reviewed.}, } @article {pmid14636270, year = {2003}, author = {Attanoos, RL and Gibbs, AR}, title = {'Pseudomesotheliomatous' carcinomas of the pleura: a 10-year analysis of cases from the Environmental Lung Disease Research Group, Cardiff.}, journal = {Histopathology}, volume = {43}, number = {5}, pages = {444-452}, doi = {10.1046/j.1365-2559.2003.01674.x}, pmid = {14636270}, issn = {0309-0167}, mesh = {Adenocarcinoma/metabolism/*pathology/secondary ; Adult ; Aged ; Biomarkers, Tumor/*analysis ; Calbindin 2 ; Carcinoma/metabolism/*pathology/secondary ; Diagnosis, Differential ; Female ; Humans ; Male ; Mesothelioma/metabolism/*pathology ; Middle Aged ; Pleural Neoplasms/metabolism/*pathology ; S100 Calcium Binding Protein G/biosynthesis ; }, abstract = {AIMS: To undertake a clinicopathological study of diffuse serosal neoplasms of epithelial histogenesis which clinically and pathologically mimic malignant pleural mesothelioma.

METHODS AND RESULTS: Over a 10-year (1990-2000) study period 53 carcinomas mimicking diffuse pleural mesothelioma ('pseudomesotheliomatous' carcinoma) were identified. The study group comprised 50 men and three females, age range 33-77 (median 68) years. In 46 (87%) cases there was a history of smoking and in 40 (76%) cases a history of asbestos exposure. Histologically the pleural 'pseudomesotheliomatous' carcinomas could be divided into two broad groups: primary pulmonary carcinomas with florid pleurotropic growth (n = 47), of which 34 (70%) were adenocarcinomas; and diffuse carcinomatous involvement of the pleura by metastatic tumour (n = 6). This latter group comprised two transitional cell carcinomas of bladder, one renal (clear) cell carcinoma, one ductal pancreatic adenocarcinoma, one prostatic adenocarcinoma and one squamous cell carcinoma of parotid gland origin. Follow-up data were available in 35 cases. Regardless of tumour type, survival was poor (median 8 months) and comparable to diffuse pleural mesothelioma.

CONCLUSIONS: Pleural 'pseudomesotheliomatous' carcinomas are uncommon (comprising 6% of referrals), pathologically heterogeneous tumours with poor prognosis. Tissue diagnosis should be obtained in all cases of suspected diffuse pleural neoplasia. By light microscopy and immunophenotype many of the tumours mimicked malignant mesothelioma. In particular, an awareness that all neoplasms exhibiting squamous differentiation may express cytokeratin 5/6 and thrombomodulin is important to prevent misinterpretation. In this respect, calretinin is regarded as the most specific and sensitive mesothelial marker. Misdiagnosis may have medico-legal implications in asbestos-related compensation claims.}, } @article {pmid14635504, year = {2003}, author = {Tossavainen, A}, title = {National mesothelioma incidence and the past use of asbestos.}, journal = {Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace}, volume = {59}, number = {2}, pages = {146-149}, pmid = {14635504}, issn = {1122-0643}, mesh = {Asbestos/supply & distribution ; Global Health ; Humans ; Incidence ; Mesothelioma/*epidemiology/etiology ; Occupational Exposure ; Pleural Neoplasms/*epidemiology/etiology ; }, abstract = {In Western Europe, Scandinavia, North America and Australia the manufacture and use of asbestos products peaked in the 1970's. The current incidence of mesothelioma ranges from 14 to 35 cases/million/year in eleven industrialized countries which had used asbestos 2.0 to 5.5 kg/capita/year about 25 years earlier. A significant linear correlation (r = 0.80, p = 0.01) exists between the two variables. Accordingly, about 170 tons of produced and consumed asbestos will cause at least one death from mesothelioma, most often as a consequence of occupational exposure.}, } @article {pmid14634783, year = {2003}, author = {Kebapci, M and Vardareli, E and Adapinar, B and Acikalin, M}, title = {CT findings and serum ca 125 levels in malignant peritoneal mesothelioma: report of 11 new cases and review of the literature.}, journal = {European radiology}, volume = {13}, number = {12}, pages = {2620-2626}, pmid = {14634783}, issn = {0938-7994}, mesh = {Adult ; CA-125 Antigen/*blood ; Diagnosis, Differential ; Female ; Humans ; Male ; Mesothelioma/*blood/*diagnostic imaging ; Middle Aged ; Peritoneal Neoplasms/*blood/*diagnostic imaging ; Retrospective Studies ; Tomography, X-Ray Computed ; }, abstract = {The aim of this study was to review and reappraise the clinical and CT features of malignant peritoneal mesothelioma (MPM), and to discuss differential diagnosis. The history, clinical, and laboratory data, and imaging studies of 11 patients with a histologically proven diagnosis of MPM, were retrospectively reviewed. Our patients consisted of 7 women and 4 men, with a median age of 48 years (age range 40-55 years). There was a definite history of significant asbestos exposure in 6 patients. Abdominal swelling (9 of 11) was the most common presenting symptom. The mean serum CA-125 (normal value 1.2-32 U/ml) level was 230 U/ml (range 19-1000 U/ml). The most common radiological findings were extensive or moderate amounts ascites (11 of 11), irregular or nodular peritoneal thickening (11 of 11), omental involvement (10 of 11), mesentery involvement (9 of 11), pleural thickening, plaques or calcification (7 of 11), pleural effusion (6 of 11), and bowel wall thickening (5 of 11). Two patients had large upper abdominal masses. Computed tomography findings of MPM are nonspecific and inadequate to pinpoint specific diagnosis. The diagnosis requires histological demonstration which is commonly made by an image or laparoscopic-guided biopsy. Pleural changes suggesting asbestosis combined with CT findings and high CA-125 levels can suggest, but are not diagnostic of, mesothelioma. Suggesting the diagnosis of MPM is important because histological and immunohistochemical tests are needed for diagnostic accuracy.}, } @article {pmid14634182, year = {2003}, author = {Lewis, RJ and Schnatter, AR and Drummond, I and Murray, N and Thompson, FS and Katz, AM and Jorgensen, G and Nicolich, MJ and Dahlman, D and Thériault, G}, title = {Mortality and cancer morbidity in a cohort of Canadian petroleum workers.}, journal = {Occupational and environmental medicine}, volume = {60}, number = {12}, pages = {918-928}, pmid = {14634182}, issn = {1470-7926}, mesh = {Adult ; Canada/epidemiology ; Cause of Death ; Cohort Studies ; *Extraction and Processing Industry ; Female ; Humans ; Hydrocarbons/toxicity ; Hydrogen Sulfide/toxicity ; Incidence ; Male ; *Mortality ; Neoplasms/*epidemiology/etiology ; Occupational Diseases/*epidemiology/etiology ; Occupational Exposure/adverse effects ; *Petroleum ; Risk Assessment ; Sex Distribution ; Time Factors ; }, abstract = {AIMS: To assess mortality and cancer morbidity in Canadian petroleum workers and explore exposure-response relations for specific petroleum agents.

METHODS: A total of 25 292 employees hired between 1964 and 1994 were linked to the Canadian tumour registry and national mortality database. Exposure-response trends were assessed for hydrocarbon solvents/fuels, hydrocarbon lubricants, petroleum coke/spent catalyst, and hydrogen sulphide (H2S).

RESULTS: External comparison analyses (mortality and incidence) showed deficits for all causes and all malignant neoplasms combined and were consistent with expectation for most malignant and non-malignant sites analysed. Gall bladder cancer mortality was increased among males based on four deaths, but cases had no common job assignments and the increase was focused in workers employed <10 years. Mesothelioma incidence was increased. Most exposure-specific analyses were compromised by small numbers. Statistically significant increases were observed for H2S exposure and a subgroup of accidental deaths as well as for petroleum coke/spent catalyst exposure and lung cancer. While both findings have a degree of biologic plausibility, the H2S association, which exhibited a clearer exposure-response pattern, could be subject to unmeasured confounders. Additionally, interpretation was complicated by the high correlation between hydrocarbon and H2S exposures. With regard to lung cancer, the analysis could not adequately control for smoking, was based on small numbers, and exhibited a tenuous exposure-response pattern.

CONCLUSION: The findings for mesothelioma suggest the need for continued attention to asbestos in the petroleum industry. The relation between accidental deaths and H2S exposure deserves closer scrutiny in similarly exposed populations. Further analyses of lung cancer are underway and will be reported separately.}, } @article {pmid14630441, year = {2003}, author = {Robinson, BW and Creaney, J and Lake, R and Nowak, A and Musk, AW and de Klerk, N and Winzell, P and Hellstrom, KE and Hellstrom, I}, title = {Mesothelin-family proteins and diagnosis of mesothelioma.}, journal = {Lancet (London, England)}, volume = {362}, number = {9396}, pages = {1612-1616}, doi = {10.1016/S0140-6736(03)14794-0}, pmid = {14630441}, issn = {1474-547X}, support = {CA 79490/CA/NCI NIH HHS/United States ; CA 85780/CA/NCI NIH HHS/United States ; CA 98008/CA/NCI NIH HHS/United States ; }, mesh = {Antigens, Neoplasm/*blood ; Asbestos ; Biomarkers, Tumor/*blood ; Environmental Exposure ; GPI-Linked Proteins ; Humans ; Lung Diseases/blood ; Lung Neoplasms/blood ; Membrane Glycoproteins/*blood ; Mesothelin ; Mesothelioma/*blood/diagnosis ; Pleural Diseases/blood ; Pleural Neoplasms/*blood ; }, abstract = {BACKGROUND: Mesothelioma is a highly aggressive tumour for which there are no reliable serum tumour markers. Identification of such a marker would be useful in diagnosis of mesothelioma and for monitoring responses to treatment and screening at-risk individuals.

METHODS: We assayed serum concentrations of soluble mesothelin-related proteins (SMR) using a double determinant (sandwich) ELISA in a blinded study of serum samples from 44 patients with histologically proven mesothelioma; 68 matched healthy controls, 40 of whom had been exposed to asbestos; and 160 patients with other inflammatory or malignant lung and pleural diseases.

FINDINGS: 37 (84%) of 44 patients with mesothelioma had raised concentrations of SMR at a serum dilution of 1/80, compared with three (2%) of 160 patients with other cancers or other inflammatory lung or pleural diseases, and with none of 28 controls who had not been exposed to asbestos. SMR concentrations correlated with tumour size and increased during tumour progression. Seven of the 40 asbestos-exposed individuals had increased serum concentrations of SMR; three of those seven developed mesothelioma and one developed lung carcinoma within 1-5 years. None of the 33 asbestos-exposed participants whose serum samples had normal concentrations of SMR and who were followed up over 8 years developed mesothelioma.

INTERPRETATION: Determination of SMR in serum could be a useful marker for diagnosis of mesothelioma and to monitor disease progression. It might also prove helpful for screening asbestos-exposed individuals for early evidence of mesothelioma.}, } @article {pmid14628861, year = {2003}, author = {Chung, DJ and Kang, YW and Kim, BK and Park, JY and An, YS and Yang, JM and Kim, JH}, title = {Deciduoid peritoneal mesothelioma: CT findings with pathologic correlation.}, journal = {Abdominal imaging}, volume = {28}, number = {5}, pages = {614-616}, doi = {10.1007/s00261-003-0006-1}, pmid = {14628861}, issn = {0942-8925}, mesh = {Female ; Humans ; Mesothelioma/*diagnostic imaging/pathology ; Middle Aged ; Peritoneal Neoplasms/*diagnostic imaging/pathology ; Photomicrography ; *Tomography, X-Ray Computed ; }, abstract = {We report a rare case of deciduoid peritoneal mesothelioma in a 47-year-old woman who had no history of asbestos exposure or previous surgery. Immunohistochemistry and electron microscopic findings showed that the tumor was a subtype of epithelioid mesothelioma. Awareness of this disease entity is helpful for the differential diagnosis of peritoneal masses.}, } @article {pmid14628425, year = {2003}, author = {Le, DT and Deavers, M and Hunt, K and Malpica, A and Verschraegen, CF}, title = {Cisplatin and irinotecan (CPT-11) for peritoneal mesothelioma.}, journal = {Cancer investigation}, volume = {21}, number = {5}, pages = {682-689}, doi = {10.1081/cnv-120023766}, pmid = {14628425}, issn = {0735-7907}, mesh = {Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Camptothecin/administration & dosage/*analogs & derivatives ; Cisplatin/administration & dosage ; Female ; Humans ; Infusions, Intravenous ; Infusions, Parenteral ; Irinotecan ; Male ; Mesothelioma/*drug therapy/pathology ; Middle Aged ; Peritoneal Neoplasms/*drug therapy/pathology ; Retrospective Studies ; }, abstract = {Peritoneal mesothelioma is a rare malignancy that is seen in patients exposed to asbestos or in young women with no known exposure to asbestos. The clinical features of the disease are similar in these two groups, and include peritoneal carcinomatosis, ascites, thrombocytemia, systemic symptoms (fever and night sweats), and hypercoagulability. There is no known curative therapy for this disease. Cisplatin has activity in 25% of patients. Mesothelial cells are known to contain high levels of carboxylesterase, a key enzyme in the activation of Irinotecan (CPT-11) to SN-38. This retrospective review of our experience in combining cisplatin 50 or 60 mg/m2 i.v. or i.p. on day 1 with CPT-11 50 or 60 mg/m2 i.v. on day 1, 8, and 15. Courses were repeated every 4 weeks x 6. If i.p. administration of cisplatin were feasible, it was the preferred route. Response to treatment was based on RECIST criteria. Fourteen men and 3 women, median age 62 years (35-76 years) and median PS 1 (0-2) were treated. Median number of courses was two for nonresponders and six for responders. The overall response rate was 24%, but 76% of patients improved on treatment. Median survival is not reached. Grade > or = 2 side effects included anemia (n = 6), neutropenia (n = 3), nausea/vomiting (n = 4), and constipation (n = 2). Grade 1 side effects were fatigue, anorexia, weight loss, alopecia, diarrhea, neuropathy, and gastric reflux. There were no grade > or = 3 hematologic toxicities. The combination of cisplatin and CPT-11 is well tolerated and has clinical benefits in patients with peritoneal mesothelioma.}, } @article {pmid14620669, year = {2003}, author = {Marsh, GM and Gula, MJ and Roggli, VL and Churg, A}, title = {The role of smoking and exposure to asbestos and man-made vitreous fibers in a questionable case of mesothelioma.}, journal = {Industrial health}, volume = {41}, number = {4}, pages = {332-334}, doi = {10.2486/indhealth.41.332}, pmid = {14620669}, issn = {0019-8366}, mesh = {Aged ; Asbestos/*adverse effects/analysis ; Humans ; Lung/pathology ; Male ; Medical History Taking ; Mesothelioma/diagnosis/*etiology ; Mineral Fibers/adverse effects/analysis ; Occupational Diseases/diagnosis/*etiology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/diagnosis/*etiology ; Risk Factors ; Smoking/*adverse effects ; }, abstract = {A remaining uncertainty in the U.S. cohort study of man-made vitreous fiber (MMVF) workers is whether asbestos exposure contributed to 10 questionable cases of mesothelioma. We report further details on one case from our previous mesothelioma investigation, including results of a recent lung tissue analysis. Case is a 68 year-old white male employed 1951-54 in a rock/slag wool plant where asbestos-containing products were manufactured. Cause of death was recorded as "mesothelioma, malignant, right pleural cavity" (ICD9: 163.9). Analysis for presence of asbestos bodies identified 18,300 asbestos bodies per gram of wet lung tissue (AB/gm), which greatly exceeds the normal range of 0-20 AB/gm. No MMVFs were identified in this sample. We conclude that this patient's tumor was not a mesothelioma, but a carcinoma possibly arising in the lung or mediastinum, and that this case supports the view that the few suspected mesotheliomas found in the U.S. cohort may have been caused by asbestos exposure.}, } @article {pmid14620285, year = {2003}, author = {García de Jalón, A and Gil, P and Azúa-Romeo, J and Borque, A and Sancho, C and Rioja, LA}, title = {Malignant mesothelioma of the tunica vaginalis. Report of a case without risk factors and review of the literature.}, journal = {International urology and nephrology}, volume = {35}, number = {1}, pages = {59-62}, pmid = {14620285}, issn = {0301-1623}, mesh = {Aged ; Humans ; Male ; Mesothelioma/*pathology ; Risk Factors ; Testicular Neoplasms/*pathology ; }, abstract = {Malignant mesothelioma of the tunica vaginalis testis is an aggressive tumour with local recurrence being distant metastases the main feature of the clinical course. Usually appears over the fourth decade, having a strong relationship with occupational exposure to asbestos and long lasting hydrocele. We introduce a case of a 78-year-old caucasian male who developed a malignant mesothelioma without personal history of hydrocele or exposure to asbestos. A revision of the current literature is performed to summarize the recent therapeutic options as well as new diagnostic tools.}, } @article {pmid14617514, year = {2004}, author = {Swain, WA and O'Byrne, KJ and Faux, SP}, title = {Activation of p38 MAP kinase by asbestos in rat mesothelial cells is mediated by oxidative stress.}, journal = {American journal of physiology. Lung cellular and molecular physiology}, volume = {286}, number = {4}, pages = {L859-65}, doi = {10.1152/ajplung.00162.2003}, pmid = {14617514}, issn = {1040-0605}, mesh = {Animals ; Asbestos, Crocidolite/*pharmacology ; Carcinogens/*pharmacology ; Cell Line ; Enzyme Activation/drug effects ; Enzyme Inhibitors/pharmacology ; Epithelium ; Imidazoles/pharmacology ; Mitogen-Activated Protein Kinases/antagonists & inhibitors/*metabolism ; Oxidative Stress/drug effects/*physiology ; Phosphorylation ; Pleura/cytology/*drug effects/*enzymology ; Pyridines/pharmacology ; Rats ; Transcription Factor AP-1/metabolism ; p38 Mitogen-Activated Protein Kinases ; }, abstract = {Asbestos fibers are biopersistent particles that are capable of stimulating chronic inflammatory responses in the pleura of exposed individuals. Exposure of pleural mesothelial cells, the progenitor cell of malignant mesothelioma, to asbestos induces an array of cellular responses. The present studies investigated whether the p38 mitogen-activated protein kinase cascade was induced under asbestos-exposed conditions. p38 plays a vital role in the response to stressful stimuli and enables the cell to enter an inflammatory state characterized by cytokine production. Western blot and in vitro kinase assays showed increases in dual phosphorylation and actual activity of p38 after exposure to fibrous and nonfibrous (milled) crocidolite; in contrast, polystyrene beads and iron (III) oxide had no such effects. In common with other asbestos-induced events, this was shown to be an oxidative stress-sensitive effect, inasmuch as preincubation with N-acetyl-L-cysteine or -tocopherol (vitamin E) ameliorated the effect. The present studies show that p38 activity is important for crocidolite-induced activator protein-1 DNA binding, inasmuch as an inhibitor of p38, SB-203580, reduced this activity. Crocidolite-induced cytotoxicity was also reduced with SB-203580, indicating a role for p38 in asbestos-mediated cell death. Our studies suggest that p38 activity could be a crucial factor in the chronic immune response elicited by asbestos and may represent a target for future pharmacological intervention.}, } @article {pmid14606638, year = {2003}, author = {Ascoli, V and Belli, S and Carnovale-Scalzo, C and Corzani, F and Facciolo, F and Lopergolo, M and Nardi, F and Pasetto, R and Comba, P}, title = {Malignant mesothelioma in Rome and Latium region, 1993-2001.}, journal = {Tumori}, volume = {89}, number = {4}, pages = {377-381}, doi = {10.1177/030089160308900405}, pmid = {14606638}, issn = {0300-8916}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Incidence ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology/mortality ; Middle Aged ; Rome/epidemiology ; Sex Distribution ; }, abstract = {AIMS AND BACKGROUND: Epidemiological studies on malignant mesothelioma have provided evidence on the etiologic role of occupational asbestos exposure and, to some extent, domestic and residential exposures. Less attention has been given to the occurrence of mesothelioma in urban areas where large quantities of asbestos have been employed in the past. The purpose of the study was to investigate the occurrence of mesothelioma in patients living in the urban area of Rome and in other parts of the Latium Region and the patterns of asbestos exposure.

METHODS AND STUDY DESIGN: A pathology-based, malignant mesothelioma archive operating in Rome, Italy, was the source of cases. Included in the survey were cases resident in Latium and diagnosed in the period January 1, 1993, through December 31, 2001. Information on asbestos exposure was derived from interviews to the patient or his/her next of kin and from available medical records.

RESULTS: The case series included: 114 males and 53 females; total, 167. Information on asbestos exposure was available for 138 cases (83%). Occupational exposure was ascertained or suspected for 33% of cases resident in Rome and 63% of those resident in other municipalities of Latium. Sex ratio was 1.6 in Rome and 3.3 in Latium.

CONCLUSIONS: The high prevalence of women among mesothelioma cases and lower proportion of occupational exposure in Rome versus the other municipalities of Latium suggest a possible role of environmental asbestos exposure in the urban area.}, } @article {pmid14605068, year = {2003}, author = {Edwards, JG and Swinson, DE and Jones, JL and Muller, S and Waller, DA and O'Byrne, KJ}, title = {Tumor necrosis correlates with angiogenesis and is a predictor of poor prognosis in malignant mesothelioma.}, journal = {Chest}, volume = {124}, number = {5}, pages = {1916-1923}, doi = {10.1378/chest.124.5.1916}, pmid = {14605068}, issn = {0012-3692}, mesh = {Female ; Humans ; Male ; Mesothelioma/blood supply/mortality/*pathology ; Middle Aged ; Multivariate Analysis ; Necrosis ; Neovascularization, Pathologic/*pathology ; Pleural Neoplasms/blood supply/mortality/*pathology ; Prognosis ; Proportional Hazards Models ; Survival Rate ; }, abstract = {OBJECTIVES: Malignant mesothelioma (MM) is a fatal tumor of increasing incidence related to asbestos exposure. Microscopic tumor necrosis (TN) is a poor prognostic factor in solid tumors, but it has not been characterized in MM. We wished to evaluate the incidence of TN in MM and its correlations with clinicopathologic factors, angiogenesis, and survival.

METHODS: TN was graded in 171 routine formalin-fixed, paraffin-embedded hematoxylin-eosin-stained tumor sections by two independent observers. Angiogenesis was assessed by the microvessel count (MVC) of CD34 immunostained sections. TN was correlated with survival by Kaplan-Meier and log-rank analysis, and stepwise, multivariate Cox models were used to compare TN with angiogenesis and established prognostic factors and prognostic scoring systems.

RESULTS: TN was identified in 39 cases (22.8%) and correlated with low hemoglobin (p = 0.01), thrombocytosis (p = 0.04), and high MVC (p = 0.02). TN was a poor prognostic factor in univariate analysis (p = 0.008). Patients with TN had a median survival of 5.3 months vs 8.3 months in negative cases. Independent indicators of poor prognosis in multivariate analysis were nonepithelioid cell type (p = 0.0001), performance status > 0 (p = 0.007), and increasing MVC (p = 0.004) but not TN. TN contributed independently to the European Organisation for Research and Treatment of Cancer (EORTC) [p = 0.03] and to the Cancer and Leukemia Group B (CALGB) [p = 0.03] prognostic groups in respective multivariate Cox analyses.

CONCLUSIONS: TN correlates with angiogenesis and is a poor prognostic factor in MM. TN contributes to the EORTC and CALGB prognostic scoring systems.}, } @article {pmid14592528, year = {2004}, author = {Mutsaers, SE}, title = {The mesothelial cell.}, journal = {The international journal of biochemistry & cell biology}, volume = {36}, number = {1}, pages = {9-16}, doi = {10.1016/s1357-2725(03)00242-5}, pmid = {14592528}, issn = {1357-2725}, mesh = {Animals ; Cell Transformation, Neoplastic ; Epithelial Cells/pathology/*physiology ; Epithelium/pathology/*physiology/ultrastructure ; Humans ; Mesothelioma/etiology/*pathology ; Microvilli/ultrastructure ; Models, Biological ; Serous Membrane/cytology/*physiology ; }, abstract = {Mesothelial cells form a monolayer of specialised pavement-like cells that line the body's serous cavities and internal organs. The primary function of this layer, termed the mesothelium, is to provide a slippery, non-adhesive and protective surface. However, mesothelial cells play other pivotal roles involving transport of fluid and cells across the serosal cavities, antigen presentation, inflammation and tissue repair, coagulation and fibrinolysis and tumour cell adhesion. Injury to the mesothelium triggers events leading to the migration of mesothelial cells from the edge of the lesion towards the wound centre and desquamation of cells into the serosal fluid which attach and incorporate into the regenerating mesothelium. If healing is impaired, fibrous serosal adhesions form between organs and the body wall which impede vital intrathoracic and abdominal movement. Neoplastic transformation of mesothelial cells gives rise to malignant mesothelioma, an aggressive tumour predominantly of the pleura. Although closely associated with exposure to asbestos, recent studies have implicated other factors including simian virus 40 (SV40) in its pathogenesis.}, } @article {pmid14582277, year = {2003}, author = {Bernardini, P and Schettino, B and Sperduto, B and Giannandrea, F and Burragato, F and Castellino, N}, title = {[Three cases of pleural mesothelioma and environmental pollution with tremolite outcrops in Lucania].}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {25}, number = {3}, pages = {408-411}, pmid = {14582277}, issn = {1592-7830}, mesh = {Aged ; Aged, 80 and over ; Asbestos, Amphibole/*adverse effects ; Environmental Pollution/*adverse effects ; Female ; Humans ; Italy ; Male ; Mesothelioma/*etiology ; Middle Aged ; Pleural Neoplasms/*etiology ; }, abstract = {In a circumscribed rural area of Lucania (Italy) three cases of pleural mesothelioma have been identified: two men, 83 and 52 years old and a 78 year-old woman, who all had in common the fact of being shepards in that area. Possible asbestos pollution sources have been sought: we have immediately excluded an asbestos manufactured articles pollution, however we have highlighted the presence of "green stones", which had always been known to the local inhabitants and which, in three subsequent campains of collecting and chemical-mineralogical investigations, have resulted partly constituted by amphibole asbestos, classified as tremolite. Official institutions are organising a series of initiatives to verify the hypothesis of a causal relationship between the presence of tremolite and the cases of pleural mesothelioma, and preventive initiatives aimed at reducing exposure and to a sanitary surveillance. Similar problems had been identified in Turkey, Greece, Corsica, New Caledonia and recently in eastern Sicily.}, } @article {pmid14582276, year = {2003}, author = {Comba, P and Bruno, C and Pasetto, R}, title = {[Indications of public health in areas naturally polluted with asbestiform fibers].}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {25}, number = {3}, pages = {405-407}, pmid = {14582276}, issn = {1592-7830}, mesh = {*Asbestos, Amphibole ; Environmental Exposure/*prevention & control ; Environmental Pollution/*prevention & control ; Humans ; Italy ; *Mineral Fibers ; *Public Health ; }, abstract = {Adverse health effects of naturally occurring asbestiform fibres have been reported since the Seventies in various countries. The present paper describes the case of Biancavilla, a municipality located in Eastern Sicily, where the occurrence of the amphibolic fibre fluoro-edenite has been associated to a cluster of pleural mesotheliomas. The public health recommendations aimed at reducing exposure to fluoroedenite are described. This case study shows the importance of public-driven remedial action, including interruption of activities of previously operating quarries and asphalt paving of roads, in influencing population's compliance to recommendations aimed at modifying individual behaviours. In order to pursue the goal of fostering community's autonomy in decision making, the optimal approach is ensuring timely and transparent information dissemination.}, } @article {pmid14582275, year = {2003}, author = {Mirabelli, D and Magnani, C}, title = {[Interaction between occupational and environmental exposure to asbestos. Epidemiologic survey].}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {25}, number = {3}, pages = {402-404}, pmid = {14582275}, issn = {1592-7830}, mesh = {Asbestos/*adverse effects ; Environmental Exposure/*adverse effects ; Female ; Humans ; Italy ; Male ; Mesothelioma/*epidemiology/etiology ; Occupational Diseases/*epidemiology/etiology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*epidemiology/etiology ; }, abstract = {In this short review we present the evidence of association of Malignant Mesothelioma and asbestos exposure in Italy, with focus on environmental exposure. After almost 10 years from the cessation of industrial use of asbestos, areas of high incidence attributable to environmental exposure are still observed.}, } @article {pmid14582274, year = {2003}, author = {Silvestri, S and Seniori Costantini, A}, title = {[Asbestos risk: past and present exposure].}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {25}, number = {3}, pages = {398-401}, pmid = {14582274}, issn = {1592-7830}, mesh = {Asbestos/*adverse effects ; Female ; Humans ; Italy ; Male ; Occupational Diseases/*epidemiology ; Occupational Exposure/*statistics & numerical data ; Risk Factors ; }, abstract = {Occupational asbestos exposure affected a large number of workers during the last century. In particular, during the period following the second world war until the end of the eighties heavy exposures occurred in several industrial divisions. An approximate data can be represented by the number of requests for compensation according to the n. 257/1992 ban asbestos law. The National and Regional Mesothelioma Registries collect all the cases of this asbestos related disease. Analysing these data, the industrial divisions at risk, considering both intensity and quality of exposure, emerge with increasing accuracy. The use of asbestos in new products has been banned in Italy since 1992. The legislation issued during the nineties includes technical guidelines for exposure risk control during operations on asbestos containing products, mainly consisting in maintenance or asbestos removal. Consequently, the exposures decreased, both in terms of intensity and in terms of number of exposed workers but exposures will reach a complete end only when asbestos is completely cleared out. In this paper, data about industrial divisions at major risk, derived from the tuscanian cases, as well as the list of the jobs of the present asbestos exposed workers are illustrated.}, } @article {pmid14582272, year = {2003}, author = {Musti, M}, title = {[The mesothelioma registry].}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {25}, number = {3}, pages = {393-395}, pmid = {14582272}, issn = {1592-7830}, mesh = {Asbestos/adverse effects ; Environmental Exposure/adverse effects ; Female ; Humans ; Italy ; Male ; Mesothelioma/*epidemiology/etiology ; *Registries ; }, abstract = {The National Mesothelioma Registry (RENAM) have as mains objectives: estimate of the incidence of malignant mesothelioma cases in Italy, collecting information on past exposure to asbestos, impact and spread of the disease among population, identification of unexpected or unknown sources of contamination and promotion of research on asbestos exposure and mesothelioma. Some data of Puglia Regional Operating Centre are reported. Use of Renam as epidemiological surveillance system is underlined in respect to public health and scientific research.}, } @article {pmid14571437, year = {2003}, author = {Marchevsky, AM and Wick, MR}, title = {Current controversies regarding the role of asbestos exposure in the causation of malignant mesothelioma: the need for an evidence-based approach to develop medicolegal guidelines.}, journal = {Annals of diagnostic pathology}, volume = {7}, number = {5}, pages = {321-332}, doi = {10.1016/s1092-9134(03)00078-9}, pmid = {14571437}, issn = {1092-9134}, mesh = {Animals ; Asbestos/*toxicity ; Disease Models, Animal ; Environmental Exposure/*adverse effects/legislation & jurisprudence ; *Evidence-Based Medicine ; *Guidelines as Topic ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Rats ; }, abstract = {Asbestos is a group of fibrous silicate minerals that includes two mineralogic groups: amphiboles and serpentines. While the carcinogenic role of amphiboles (eg, crocidolite and amosite) is well established, medical "experts" that tend to strongly advocate their views currently argue in medicolegal cases multiple specific issues regarding the carcinogenicity of asbestos fibers. For example, it is controversial whether chrysotile causes malignant mesothelioma (MM); what are the specific carcinogenic thresholds for amphiboles and chrysotile; what occupations are truly at risk to develop MM as a result of asbestos exposure; what is the role of chrysotile in the development of peritoneal MM; how to assign causation in individuals exposed to multiple industrial products containing variable concentrations of various asbestos fibers; and, what criteria should be used to accept causation in household exposure cases and others. The causation criteria currently acceptable in U.S. courts are surprisingly flexible and subject to variable interpretation by medical "experts." At a time where thousands of individuals are claiming causation of MM by asbestos exposure, there is a need to develop more specific causation guidelines based on scientific evidence. Evidence-based medicine has been proposed as a new approach to the study, teaching, and the practice of medicine and has been used as a process of systematically reviewing the relevant studies in the literature to assess their scientific validity and development of guidelines. This article summarizes some of the current controversies regarding the role of asbestos exposure in the causation of MM and suggests the need for future evidence-based medicine-type studies to develop causation guidelines that could be used consistently during litigation.}, } @article {pmid14569398, year = {2004}, author = {Pylkkänen, L and Wolff, H and Stjernvall, T and Knuuttila, A and Anttila, S and Husgafvel-Pursiainen, K}, title = {Reduced Fhit protein expression in human malignant mesothelioma.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {444}, number = {1}, pages = {43-48}, pmid = {14569398}, issn = {0945-6317}, mesh = {*Acid Anhydride Hydrolases ; Adult ; Aged ; Asbestos/adverse effects ; Bronchi/chemistry ; Chromosomes, Human, Pair 3 ; Epithelium/chemistry ; Female ; Gene Deletion ; *Gene Expression ; Humans ; Immunohistochemistry ; Loss of Heterozygosity ; Lung Neoplasms/chemically induced/genetics ; Male ; Mesothelioma/chemically induced/chemistry/*genetics ; Microsatellite Repeats ; Middle Aged ; Neoplasm Proteins/analysis/*genetics ; Occupational Exposure ; Polymerase Chain Reaction ; Tumor Cells, Cultured ; }, abstract = {Human malignant mesothelioma (MM) is an aggressive neoplasm related to occupational exposure to asbestos and characterised by a long latency time. Multiple chromosomal deletions and DNA losses have been revealed in MM by studies performed with karyotypic, comparative genomic hybridisation and loss of heterozygosity (LOH) analyses. Among frequently deleted chromosomal sites, LOH at chromosome 3p has been detected in MM, suggesting the presence of one or several tumour suppressor genes that have an important role in development of the disease. The FHIT (fragile histidine triad) tumour suppressor gene, located at 3p14.2, has been proposed to be a target to major human lung carcinogens, such as tobacco smoke and asbestos. Although many studies have indicated decreased Fhit protein expression in a variety of malignancies, there is no report of FHIT gene aberrations or Fhit protein abnormalities in MM. We examined expression of the Fhit protein and LOH at the FHIT gene in malignant mesothelioma. Altogether, 13 paraffin embedded MM tumours were analysed for Fhit protein expression, and 21 fresh tumours and 10 cell cultures for LOH at the FHIT gene with two intragenic microsatellite markers. All tumours showed less intense immunostaining than normal bronchial epithelium or mesothelium. Fhit expression was absent or reduced in 54% (7 of 13) of the tumours, with the weakest staining observed in poorly differentiated areas. Allele loss was seen in 3 of 10 (30%) of the MM cell lines, but only in 1 of the 21 fresh tumours studied, suggesting concealment of LOH by normal cells present in MM tumours. In conclusion, our present data indicate a frequent decrease of Fhit protein expression, thus supporting the significance of FHIT inactivation in development of MM.}, } @article {pmid14534453, year = {2003}, author = {Nurminen, M and Karjalainen, A and Takahashi, K}, title = {Estimating the induction period of pleural mesothelioma from aggregate data on asbestos consumption.}, journal = {Journal of occupational and environmental medicine}, volume = {45}, number = {10}, pages = {1107-1115}, doi = {10.1097/01.jom.0000091682.95314.01}, pmid = {14534453}, issn = {1076-2752}, mesh = {Asbestos/*toxicity ; Europe/epidemiology ; Humans ; Incidence ; Male ; Mesothelioma/epidemiology/*etiology ; Occupational Diseases/epidemiology/etiology ; Occupational Exposure/adverse effects ; Pleural Neoplasms/epidemiology/*etiology ; Poisson Distribution ; Risk ; Time Factors ; World Health Organization ; }, abstract = {This study aimed to estimate the induction period from causal action of asbestos exposure to the manifestation of mesothelioma. We included the 9 countries for which we could find published aggregate data on the use of raw asbestos for a relevant time period. We extracted the annual numbers of cases of pleural cancer among men from the World Health Organization mortality database for those years using the International Classification of Diseases, 9th revision, classification. For the Scandinavian countries, we used published national cancer incidence data. In autoregressive Poisson regression modeling, we invoked different time lags of the mean annual use of asbestos to specify which time span produced the best correlation between the 2 time series. The ecologic analysis suggested that the most probable estimate for the mean induction period (use versus morbidity at society level) is approximately 25 years.}, } @article {pmid14516145, year = {2003}, author = {Dumortier, P and Thimpont, J and de Maertelaer, V and De Vuyst, P}, title = {Trends in asbestos body counts in bronchoalveolar lavage fluid over two decades.}, journal = {The European respiratory journal}, volume = {22}, number = {3}, pages = {519-524}, doi = {10.1183/09031936.03.00001903}, pmid = {14516145}, issn = {0903-1936}, mesh = {Asbestos/*analysis ; Asbestosis/*epidemiology ; Belgium/epidemiology ; Bronchoalveolar Lavage Fluid/*chemistry ; Databases, Factual ; Female ; Humans ; Linear Models ; Male ; Mesothelioma/epidemiology ; Middle Aged ; Occupational Exposure ; Pleural Neoplasms/epidemiology ; Time Factors ; }, abstract = {As in most western countries, the use of asbestos has decreased in Belgium since the mid 1970's. Successive regulations have lowered the permissible levels of exposure and prohibited the use of various asbestos products. In order to assess the impact of these prevention measures on the pulmonary fibre burden of asbestos-exposed patients, the bronchoalveolar lavage fluid (BALF) asbestos body (AB) analysis database of the authors' laboratory was reviewed for the period 1983-2000. A total of 4,772 cases were considered, of which 95% were males. AB concentration exceeded 1 AB x mL BALF(-1) in 36.1%. There was essentially no change in the mean concentration of AB over the period evaluated. However, the concentrations in individuals with very high levels decreased over time. This was associated with a shift in exposure categories from primary asbestos workers to those exposed during handling of asbestos-containing materials or to asbestos in place in buildings or industrial sites. This is consistent with epidemiological data indicating that the number of severe cases of asbestosis caused by very high cumulated doses decreases but that benign pleural diseases and mesothelioma remain the most frequent asbestos-related diseases. Past prevention measures are not expected to have a measurable influence on the incidence of mesothelioma in the near future.}, } @article {pmid14515425, year = {2003}, author = {Cvitanović, S and Znaor, L and Konsa, T and Ivancević, Z and Perić, I and Erceg, M and Vujović, M and Vuković, J and Beg-Zec, Z}, title = {Malignant and non-malignant asbestos-related pleural and lung disease: 10-year follow-up study.}, journal = {Croatian medical journal}, volume = {44}, number = {5}, pages = {618-625}, pmid = {14515425}, issn = {0353-9504}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Asbestosis/epidemiology ; Cohort Studies ; Croatia/epidemiology ; Disease Progression ; Environmental Exposure/*adverse effects ; Female ; Follow-Up Studies ; Humans ; Lung Diseases/*chemically induced/diagnostic imaging/pathology ; Lung Neoplasms/chemically induced/diagnostic imaging/pathology ; Male ; Mesothelioma/*chemically induced/diagnostic imaging/pathology ; Middle Aged ; Occupational Exposure/adverse effects ; Pleural Diseases/*chemically induced/diagnostic imaging/pathology ; Pleural Neoplasms/chemically induced/diagnostic imaging/pathology ; Radiography ; Smoking ; }, abstract = {AIM: To examine the presence of radiologically visible lung and pleural changes in patients who were exposed to the asbestos dust, and to correlate the progression of these changes with the duration and intensity of exposure and smoking. We also evaluated possible correlation between non-malignant asbestos-related pleural abnormalities and the occurrence of malignant pleural mesothelioma.

METHODS: Among 7,300 patients who visited our department between 1991 and 2000 due to non-specific respiratory symptoms, we selected 2,420 with chest X-rays indicating the possible existence of non-malignant asbestos-related diseases. The selected group was followed-up for progression of radiological changes and the development of malignant pleural mesothelioma, and the changes were correlated with the intensity and duration of exposure to asbestos dust and smoking.

RESULTS: Radiological changes characteristic for non-malignant asbestos-related pleural disease or lung asbestosis were identified in 340 (14%) out of 2,420 examined patients, of whom 77 (22.6%) developed malignant pleural mesothelioma, as compared with 13 patients out of 2,080 (0.6%) without radiological signs of asbestosis or pleural changes. Twenty-three (29.9%) patients who presented with a progression of pleural disease and lung asbestosis had a very significant incidence of malignant pleural mesothelioma (p<0.001). We also found that 55 (71.4%) patients with the highest asbestos exposure level (grade 3) developed malignant pleural mesothelioma more often (p=0.044). No correlation was found between malignant pleural mesothelioma development and duration of asbestos exposure (p=0.149) or smoking habit (p=0.617). Professionally exposed patients were at 3.3-times higher relative risk (95% confidence interval, 2.28-4.75) than those who were not exposed to develop malignant pleural mesothelioma.

CONCLUSIONS: The risk of developing lung asbestosis increased with the level of exposure to asbestos dust and smoking. The risk of developing pleural disease correlated with the intensity and duration of exposure, but not with smoking. The patients with progressive pleural and parenchymal changes are at particularly high risk of developing malignant pleural mesothelioma and must be under special surveillance.}, } @article {pmid14511265, year = {2003}, author = {Attanoos, RL and Griffiths, DM and Gibbs, AR}, title = {Unusual contaminant fibres on mineral analysis.}, journal = {Histopathology}, volume = {43}, number = {4}, pages = {405-406}, doi = {10.1046/j.1365-2559.2003.01683.x}, pmid = {14511265}, issn = {0309-0167}, mesh = {Asbestos/*analysis ; Asbestosis/*diagnosis ; Drug Contamination ; Humans ; Lung/chemistry ; Lung Neoplasms/secondary ; Magnesium Silicates/*analysis ; Male ; Mesothelioma/chemistry/diagnosis/etiology ; Middle Aged ; Mineral Fibers/analysis ; Pleural Neoplasms/chemistry/diagnosis/etiology ; }, } @article {pmid14511258, year = {2003}, author = {Attanoos, RL and Thomas, DH and Gibbs, AR}, title = {Synchronous diffuse malignant mesothelioma and carcinomas in asbestos-exposed individuals.}, journal = {Histopathology}, volume = {43}, number = {4}, pages = {387-392}, doi = {10.1046/j.1365-2559.2003.01685.x}, pmid = {14511258}, issn = {0309-0167}, mesh = {Adenocarcinoma/chemistry/etiology/pathology ; Aged ; Asbestos/adverse effects/isolation & purification ; Asbestosis/complications/*pathology ; Biomarkers, Tumor/analysis ; Carcinoma/chemistry/etiology/*pathology ; Carcinoma, Small Cell/chemistry/etiology/pathology ; Carcinoma, Squamous Cell/chemistry/etiology/pathology ; Female ; Humans ; Immunohistochemistry ; Lung Neoplasms/chemistry/etiology/*pathology ; Male ; Mesothelioma/chemistry/etiology/*pathology ; Middle Aged ; Neoplasms, Multiple Primary/etiology/*pathology ; Occupational Exposure ; Pleural Neoplasms/chemistry/etiology/*pathology ; }, abstract = {AIMS: The development of synchronous diffuse malignant mesothelioma and carcinoma in individuals exposed to asbestos is rare. We report nine cases and discuss the medico-legal implications.

METHODS AND RESULTS: Five hundred patients seeking compensation for asbestos-related diffuse malignant mesothelioma were reviewed with access to post-mortem data. The study group comprised cases in which a second (non-mesothelial) neoplasm was identified. The study group comprised eight males, one female, mean age 68 years (range 60-75). All individuals gave a history of asbestos exposure. Synchronous malignant mesothelioma with carcinoma was identified in 9/500 (1.8%). Eight malignant mesotheliomas were pleural, one was primary peritoneal in origin. By morphological subtyping there were four epithelioid, three biphasic and two sarcomatoid mesotheliomas. In 6/9 (67%) the second tumour was a primary bronchogenic carcinoma (three adenocarcinomas, two squamous cell carcinomas and one small-cell carcinoma). In 3/9 (33%) the second tumour was a non-bronchogenic carcinoma (colonic, pancreatic and breast ductal adenocarcinoma). No other neoplasms were identified in the cohort of malignant mesotheliomas studied. Five persons had pathological evidence of asbestosis (four had bronchogenic carcinomas, one colorectal adenocarcinoma). Two persons with non-bronchogenic carcinomas had identifiable asbestos bodies but no interstitial fibrosis. In two cases the second neoplasms (primary bronchogenic squamous cell and small-cell carcinomas) were associated with diffuse interstitial fibrosis but no asbestos bodies were seen on light microscopy. In each case transmission electron microscopic mineral analysis revealed an asbestos fibre burden within the background population range for control subjects and well below that seen in cases of established asbestosis. These cases were considered to represent cryptogenic fibrosing alveolitis in subjects with a history of asbestos exposure.

CONCLUSIONS: Synchronous malignant mesothelioma with carcinomas in asbestos-exposed workers is rare and identified in 1.8% of 500 malignant mesotheliomas in this series. In most cases the carcinoma represents a primary bronchogenic neoplasm. Primary lung carcinomas are recognized to be asbestos related only when occurring in association with asbestosis. In this series this combination (bronchogenic carcinoma and asbestosis) was seen in four (0.8%) cases. In post-mortem cases for possible malignant mesothelioma it is important to identify any other neoplasia and determine whether it is related to asbestos. Their presence impact upon anticipated life expectancy and in the presence of malignant mesothelioma will affect the compensation settlement.}, } @article {pmid14506756, year = {2003}, author = {Polednak, AP}, title = {Geographic distribution of incident mesothelioma in Connecticut men, 1990-99.}, journal = {International journal of cancer}, volume = {107}, number = {3}, pages = {509-510}, doi = {10.1002/ijc.11401}, pmid = {14506756}, issn = {0020-7136}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos ; Connecticut/epidemiology ; Humans ; Incidence ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Occupational Exposure ; Pleural Neoplasms/*epidemiology ; Registries ; }, } @article {pmid12968311, year = {2003}, author = {Bellis, D and Belluso, E and Capella, S and Coverlizza, S and Ferraris, G}, title = {[Mineral fibers and bladder cancer. Morphological and minerological investigations in a subject without professional exposure].}, journal = {Pathologica}, volume = {95}, number = {3}, pages = {157-161}, pmid = {12968311}, issn = {0031-2983}, mesh = {Asbestos, Serpentine/*adverse effects/analysis ; Carcinoma, Transitional Cell/*etiology/ultrastructure ; Environmental Exposure ; Humans ; Male ; Microscopy, Electron, Scanning ; Middle Aged ; Mineral Fibers/analysis ; Silicates/*adverse effects/analysis ; Specimen Handling ; Urinary Bladder Neoplasms/*etiology/ultrastructure ; }, abstract = {It is confirmed that occupational and paraoccupational exposure to mineral fibres, particularly asbestos fibres, plays a fundamental role in the induction of lung cancer and pleural mesothelioma. The possible association with other human cancers (e.g. larynx cancer, gastro-intestinal cancer, uro-genital cancer and emolinfopoietic cancer) is not yet demonstrated, even if some mineral fibres are identified in tissues different from the lung ones, such as kidney, bladder, and some biological fluids (e.g. urine of subjects with occupational exposure to asbestos). The possibility of damage caused to tissues in consequence of exposure to low concentration of mineral fibres (e.g. environmental exposure) has still to be defined. In this work we report the results of a mineralogical study by means of scanning electron microscopy with microprobe of a case of bladder cancer in a subject without professional exposure to mineral fibres where asbestos bodies are identified by optical microscopy.}, } @article {pmid12967167, year = {2003}, author = {Nay, SY}, title = {Asbestos in Belgium: use and abuse.}, journal = {International journal of occupational and environmental health}, volume = {9}, number = {3}, pages = {287-293}, doi = {10.1179/oeh.2003.9.3.287}, pmid = {12967167}, issn = {1077-3525}, mesh = {Asbestos/*adverse effects/*economics ; Asbestosis/*economics/*etiology ; Belgium ; Humans ; Liability, Legal ; Lung Neoplasms/*economics/*etiology ; Malpractice ; Mesothelioma/*economics/*etiology ; *Occupational Exposure ; *Public Policy ; *Workers' Compensation ; }, abstract = {It took 50 years for Belgium to recognize asbestosis; mesothelioma and lung cancer were recognized as occupational diseases caused by asbestos in 1982 and 1999, much later than in neighboring countries. Only salaried workers can claim compensation from the Occupational Diseases Fund. The right to reparation is thus denied to most victims because many have been self-employed: mechanics, electricians, painters, roofers, carpenters, plumbers, etc. Compensation was also denied to people who became ill through exposures to the workclothes of family members or pollution from asbestos factories near their homes. The main obstacles facing asbestos victims are legal and judicial. For instance, an employer is not liable, even for gross negligence. Victims are not allowed to claim if 20 years have passed since their exposures to asbestos. Changes in Belgian legislation are sorely needed.}, } @article {pmid12967166, year = {2003}, author = {Thébaud-Mony, A}, title = {Justice for asbestos victims and the politics of compensation: the French experience.}, journal = {International journal of occupational and environmental health}, volume = {9}, number = {3}, pages = {280-286}, doi = {10.1179/oeh.2003.9.3.280}, pmid = {12967166}, issn = {1077-3525}, mesh = {Asbestos/*adverse effects/*economics ; Asbestosis/economics/etiology ; *Environment ; France ; Government ; Humans ; Industry ; *Liability, Legal ; Mesothelioma/economics/etiology ; Mining ; *Politics ; *Workers' Compensation ; }, abstract = {This paper presents the history of asbestos mining and manufacture in France, the strategies of the multinational asbestos firms to become major international participants, the failures of occupational health and safety that allowed an epidemic of asbestos-related diseases to occur, and the important social movement of the victims of asbestos exposure. The asbestos industry thrived in France until the health effects of asbestos exposure were made public. At that time, the industry had already moved its mining and manufacture to developing countries, where they were able to take advantage of limited regulation and enforcement of occupational and environmental laws. The author analyzes the compensation systems that were approached with varying degrees of success by the victims of asbestos exposure. France banned all manufacture and use of asbestos in 1997, and in the years that have followed, it has enjoyed many successes in achieving compensation for asbestos victims.}, } @article {pmid12967165, year = {2003}, author = {Aguilar-Madrid, G and Juárez-Pérez, CA and Markowitz, S and Hernández-Avila, M and Sanchez Roman, FR and Vázquez Grameix, JH}, title = {Globalization and the transfer of hazardous industry: asbestos in Mexico, 1979-2000.}, journal = {International journal of occupational and environmental health}, volume = {9}, number = {3}, pages = {272-279}, doi = {10.1179/oeh.2003.9.3.272}, pmid = {12967165}, issn = {1077-3525}, mesh = {Asbestos/*adverse effects/economics ; Carcinogens/*adverse effects/economics ; Commerce/history ; *Environmental Exposure ; Hazardous Substances ; History, 20th Century ; Humans ; Mesothelioma/*etiology/history/mortality ; Mexico ; *Occupational Exposure ; Public Policy ; United States ; }, abstract = {This study quantified asbestos use in Mexico in the past decade and evaluated available data on mortality due to malignant mesothelioma in Mexico between 1979 and 2000. Mortality data were analyzed from secondary databases of the Mexican Social Security System and the Ministry of Health. Data on the import and export of asbestos in Mexico were obtained from the Ministry of Trade and Industrial Development of Mexico. Deaths due to pleural mesothelioma significantly increased in this period. Although the import of asbestos declined, the number of Mexican products that contain asbestos tripled. Export of Mexican asbestos-containing products to Central America grew rapidly in the last ten years of the study. Mexico continues the appreciable use of asbestos and has experienced a significant increase in the occurrence of the sentinel asbestos-related disease, malignant mesothelioma. Given the many limitations to the control of hazardous work exposures in Mexico, a ban on asbestos is advocated as the most feasible means of limiting an epidemic of asbestos-related disease.}, } @article {pmid12967164, year = {2003}, author = {Paek, D}, title = {Asbestos problems yet to explode in Korea.}, journal = {International journal of occupational and environmental health}, volume = {9}, number = {3}, pages = {266-271}, doi = {10.1179/oeh.2003.9.3.266}, pmid = {12967164}, issn = {1077-3525}, mesh = {Asbestos/*adverse effects/economics/history ; Carcinogens/*adverse effects/economics/history ; History, 20th Century ; Humans ; Incidence ; Industry ; Korea ; Lung Neoplasms/epidemiology/*etiology/history ; Mesothelioma/epidemiology/*etiology/history ; *Occupational Exposure ; Public Policy ; *Workers' Compensation/history ; }, abstract = {Although asbestos mining and manufacture has occurred in Korea since the 1920s, it was not until the 1980s that the broader social democratic movement heightened public awareness of the health problems associated with exposure to asbestos. The first systematic national survey of asbestos-related diseases was conducted in 1993. In that year, the first case of asbestos-related disease was compensated by the government. This long-delayed recognition of asbestos-related disease took place in a country that already had more than 100 asbestos factories. About 40 to 50 mesothelioma cases are reported annually through the Korean Cancer Registry. Nonetheless, only six mesothelioma cases have ever been referred to the government for workers' compensation. Lung cancer is the fastest growing cancer in Korea. Over the last 15 years, mortality from lung cancer has more than tripled. Among all these lung cancer cases, only 12 have been recognized as occupational in origin and compensated accordingly.}, } @article {pmid12967163, year = {2003}, author = {Furuya, S and Natori, Y and Ikeda, R}, title = {Asbestos in Japan.}, journal = {International journal of occupational and environmental health}, volume = {9}, number = {3}, pages = {260-265}, doi = {10.1179/oeh.2003.9.3.260}, pmid = {12967163}, issn = {1077-3525}, mesh = {Asbestos/*adverse effects ; Asbestosis/*etiology/*mortality ; *Environment ; Humans ; Japan ; Mesothelioma/*etiology/*mortality ; *Occupational Exposure ; Ships ; }, abstract = {In 2002 a total ban on asbestos was announced in Japan, following many years of sporadic and variably effective measures intended to control its use in that country. A major factor in instigating the ban was public awareness raised by the publicizing of the experience of asbestos-exposed workers in the U.S. naval base and shipyards at Yokosuka, an inordinate number of whom died of asbestos-related disease. Statistics of asbestos-related disease mortality in Japan are presented. Groups prominent in the effort to establish the ban and make it effective include the Japan Occupational Safety and Health Resource Center (JOSHRC) and the Ban Asbestos Network Japan (BANJAN). Activities of these groups are described.}, } @article {pmid12967160, year = {2003}, author = {Takahashi, K and Karjalainen, A}, title = {A cross-country comparative overview of the asbestos situation in ten Asian countries.}, journal = {International journal of occupational and environmental health}, volume = {9}, number = {3}, pages = {244-248}, doi = {10.1179/oeh.2003.9.3.244}, pmid = {12967160}, issn = {1077-3525}, mesh = {Asbestos/*adverse effects ; Asbestosis/*epidemiology/*etiology ; Carcinogens/*adverse effects ; Commerce ; Humans ; *Population Surveillance ; *Public Policy ; Reference Values ; }, abstract = {Information about asbestos issues at the national level was compiled for ten Asian countries (China, Indonesia, Japan, Korea, Malaysia, Philippines, Singapore, Taiwan, Thailand, and Vietnam) regarding 1) bans and consumption levels; 2) occupational exposure limits (OELs) and medical follow-up schemes; and 3) statistics and compensation status of asbestosis and mesothelioma victims. Only Singapore and recently Japan have adopted a total ban an asbestos. China, a major producer of chrysotile, showed an increasing consumption trend, which was typical of the less industrialized countries. Considerable differences between countries existed in OELs (0.1 to 5.0 fibers/mL) and medical follow-up of exposed workers. National statistics for asbestosis and mesothelioma were available for only the industrialized countries, where reported cases as well as compensated cases were relatively few. There is need to improve the quality and quantity of information, but the available information attests to unfavorable conditions in the less industrialized countries. Hence the experience of industrialized countries regarding asbestos and its use should be utilized to the fullest to improve the situation worldwide.}, } @article {pmid12967159, year = {2003}, author = {Du Plessis, H}, title = {Asbestos's sorrowful legacy: a photoessay.}, journal = {International journal of occupational and environmental health}, volume = {9}, number = {3}, pages = {236-243}, doi = {10.1179/oeh.2003.9.3.236}, pmid = {12967159}, issn = {1077-3525}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Carcinogens/*adverse effects ; *Environmental Exposure ; Female ; Humans ; Male ; Mesothelioma/*etiology ; Middle Aged ; *Occupational Exposure ; Photography ; South Africa ; }, } @article {pmid12967156, year = {2003}, author = {Leigh, J and Driscoll, T}, title = {Malignant mesothelioma in Australia, 1945-2002.}, journal = {International journal of occupational and environmental health}, volume = {9}, number = {3}, pages = {206-217}, doi = {10.1179/oeh.2003.9.3.206}, pmid = {12967156}, issn = {1077-3525}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/adverse effects/history ; Australia/epidemiology ; Carcinogens/adverse effects/history ; *Environmental Exposure ; Epidemiologic Studies ; Female ; History, 20th Century ; Humans ; Incidence ; Industry ; Male ; Medical History Taking ; Mesothelioma/*epidemiology/etiology/history ; Middle Aged ; *Occupational Exposure ; *Population Surveillance ; Registries/*statistics & numerical data ; }, abstract = {Using register data, time trends in mesothelioma incidence in Australia from 1945 to 2002 were calculated. Incidences are reported by age, sex, anatomic site, and state of notification. Associations with occupational and environmental asbestos exposure histories and lifetime risks in different exposure categories were investigated. Lung-fiber content was measured in a subset of cases. Australia had 7,027 cases from 1945 to 2001, with 488 more in January 2002 through June 2003. Incidence rates for Australia per million population > or = 20 years old (1999) were: male 53.3; female 10.2; total 31.8. Rates have continually increased and are the highest reported national rates in the world. Western Australia had the highest rate (1999 total 47.7), but most cases arose from the two most populous eastern states, New South Wales and Victoria. In 88% of cases (male 90%, female 61%), histories of asbestos exposures were obtained. In 80% of cases with no history of exposure, TEM lung asbestos fiber counts > 200,000 fibers > 2 microm length/g dry lung were obtained, suggesting unrecognized exposure. Australia's high incidence of mesothelioma is related to high past asbestos use, of all fiber types, in a wide variety of settings. The number of cases is expected to be about 18,000 by 2020, with about 11,000 yet to appear.}, } @article {pmid12967155, year = {2003}, author = {Braun, L and Greene, A and Manseau, M and Singhal, R and Kisting, S and Jacobs, N}, title = {Scientific controversy and asbestos: making disease invisible.}, journal = {International journal of occupational and environmental health}, volume = {9}, number = {3}, pages = {194-205}, doi = {10.1179/oeh.2003.9.3.194}, pmid = {12967155}, issn = {1077-3525}, mesh = {Asbestos/*adverse effects ; Asbestosis/*etiology ; Carcinogens/*adverse effects ; *Developing Countries ; *Environmental Exposure ; Humans ; India ; Industry ; Knowledge ; Mesothelioma/*etiology/genetics/virology ; *Occupational Exposure ; *Public Policy ; Risk Factors ; Science/trends ; South Africa ; }, abstract = {Despite irrefutable evidence that asbestos causes asbestosis, lung cancer, and mesothelioma, asbestos mining, milling, and manufacturing continue. The authors discuss three scientific debates over the roles of fiber types, viruses, and genetics in the development of mesothelioma. While these controversies might appear internal to science and unconnected to policies of the global asbestos industry, they argue that scientific debates, whether or not fostered by industry, play a central role in shaping conceptualization of the problem of asbestos-related disease. In South Africa, India, and elsewhere, these controversies help to make the disease experience of asbestos-exposed workers and people in asbestos-contaminated communities invisible, allowing the asbestos industry to escape accountability for its practices.}, } @article {pmid12958733, year = {2003}, author = {Nesti, M and Marinaccio, A and Chellini, E}, title = {[Surveillance of malignant mesothelioma cases and definition of asbestos exposure: 1997 ReNaM data].}, journal = {Epidemiologia e prevenzione}, volume = {27}, number = {3}, pages = {147-153}, pmid = {12958733}, issn = {1120-9763}, mesh = {Aged ; Asbestos/*adverse effects ; Environmental Exposure/*adverse effects ; Female ; Humans ; Male ; Mesothelioma/epidemiology/*etiology ; *Population Surveillance ; *Registries ; }, abstract = {The main objectives of the National Mesothelioma Register (ReNaM), set up by the National Institute for Prevention and Occupational Safety (ISPESL), are: (a) the estimate of malignant mesothelioma incidence in Italy, (b) the definition of exposure to asbestos, (c) the identification of unknown contamination sources, still present on the territory. Cased diagnosed in 1997 in Piedmont, Liguria, Emilia-Romagna, Tuscany and Apulia are reported, regions with more than 17 million inhabitants (30% of national population). ReNaM has facilitated the identification of mesothelioma cases and the description of the previous asbestos exposure in a large geographical area of the country, even though in some regions the definition of exposure to asbestos is not complete. 429 cases are recorded, of which 326 (76%) have been defined as definite malignant mesothelioma. The standardized annual incidence rate just for pleural definite mesothelioma is 1.51 x 100,000 inhabitants (2.26 for males and 0.79 for females). The exposure to asbestos has been defined for 198 mesothelioma cases with histological diagnosis: 125 cases (63%) refer to professional exposure, 10 (5%) to environmental exposure, 5 (2.5%) to domestic exposure. The adoption of a well-constructed national database, the up-date of guidelines and the recent starting up of ReNaM in other italian regions (Lombardy, Veneto, Marche, Campania, Basilicata and Sicily) will shortly lead to obtaining a major representativeness of the Italian situation.}, } @article {pmid12925962, year = {2003}, author = {Ulvestad, B and Kjaerheim, K and Møller, B and Andersen, A}, title = {Incidence trends of mesothelioma in Norway, 1965-1999.}, journal = {International journal of cancer}, volume = {107}, number = {1}, pages = {94-98}, doi = {10.1002/ijc.11357}, pmid = {12925962}, issn = {0020-7136}, mesh = {Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Cohort Studies ; Female ; Humans ; Incidence ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Norway/epidemiology ; Pleural Neoplasms/*epidemiology/etiology ; Risk Factors ; Time Factors ; }, abstract = {Asbestos exposure is considered to be the only important risk factor for malignant mesothelioma. The importation of asbestos to Norway increased after World War II and peaked in 1970. Stringent regulations took effect in 1977, and importation and use of asbestos practically ended in Norway in the late 1970s, until importation was prohibited in 1982. Our study aimed to analyze the incidence of mesothelioma in Norway according to temporal variation, to study the consequences of the use of asbestos and the asbestos ban effectiveness. An age-period-cohort model was used to analyze time trends for pleural mesotheliomas. From 1965-1999, the annual number of pleural mesotheliomas rose gradually both in males and females, and the highest annual number of pleural mesotheliomas was recorded in 1999 with 73 new cases diagnosed. The age-adjusted log linear drift of malignant mesothelioma of the pleura during the observation period rose 31.1% per 5 years among men and 15.9% among women. In 1995-1999, the age-adjusted incidence rate for men was 16.6 per million person-years for men and 2.3 for women. Cohort-specific risks increased for men born up to around 1935. After this the risks seem to stabilize. The rates were determined by age and by birth cohort. The delayed period effect of the asbestos regulation by the late 1970s will probably have its greatest effects on the mesothelioma rates around 2010.}, } @article {pmid12910880, year = {2003}, author = {Melino, C}, title = {[The registry for asbesto-related tumors].}, journal = {Annali di igiene : medicina preventiva e di comunita}, volume = {15}, number = {3}, pages = {271-274}, pmid = {12910880}, issn = {1120-9135}, mesh = {Adolescent ; Adult ; Aged ; Asbestos/*adverse effects ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Italy/epidemiology ; Male ; Middle Aged ; Neoplasms/*epidemiology/*etiology ; *Registries ; }, abstract = {The author stresses the importance of DPCM 10 December 2002 no.308, which determines the format and the rules to fill the registry for the cases of asbestos-related mesothelioma, according to art 36, comma 3, DLgs 277/91. The Author admits the usefulness of such a registry, but comments that its official approval came very late, because it actually was started in 1993 by ISPESL (The Higher Institute for Prevention and Safety of Labor), after the approval of DLgs 277/91. According to ISPESL initiative, all cases of mesothelioma and related circumstances were (and are) collected through a periferal information net operated by COR's.}, } @article {pmid19667453, year = {1998}, author = {Rafnsson, V and Benediktsdottir, KR}, title = {[Incidence of malignant mesothelioma in Iceland 1965-1995.].}, journal = {Laeknabladid}, volume = {84}, number = {6}, pages = {474-482}, pmid = {19667453}, issn = {0023-7213}, abstract = {OBJECTIVES: The aim of the study was to estimate the incidence of malignant mesothelioma in Iceland 1965-1995, as malignant mesothelioma is considered an indicator of past asbestos exposure in the population.

MATERIAL AND METHODS: All histological and obduction reports were reviewed and all specimens were reevaluated from patients with the diagnosis of malignant mesothelioma reported to the Cancer Registry or found in the files of the Department of Pathology in the University Hospital in Reykjavik since 1984. Crude annual incidence was calculated on the basis of number of cases and mean population of men and women. Information on import of goods which among other things contained asbestos was obtained from the Statistics of Iceland.

RESULTS: Twenty patients with malignant mesothelioma were found, seven women and 13 men. The annual incidence of malignant mesothelioma was 0.75 per 100 thousand for men and 0.27 for women during 1980-1995. The incidence seems to have increased in the past 30 years. Eight of the 20 patients had other causes of death coded on the death certificate. The import of goods containing asbestos decreased with the introduction of the asbestos ban, it has however increased again since 1990. Conlusions: The incidence of malignant mesothelioma seems to be increasing in Iceland which indicates that there is yet not a reduction of the influence of previous asbestos exposure. This is to be expected as there is a relatively short time since the use of asbestos decreased. The incidence here is on the same level as in Finland, but is lower than found recently in studies from Norway and US. It is suggested that physicians should pay more attention to past exposure of their cancer patients, as such exposure, occupational or other, may be relevant for the development of the cancer.}, } @article {pmid14339009, year = {1965}, author = {STEEL, SJ and BOYD, J}, title = {PLEURAL CALCIFICATION AND MESOTHELIOMA FOLLOWING EXPOSURE TO ASBESTOS.}, journal = {British journal of diseases of the chest}, volume = {59}, number = {}, pages = {130-132}, doi = {10.1016/s0007-0971(65)80002-x}, pmid = {14339009}, issn = {0007-0971}, mesh = {*Asbestos ; *Asbestosis ; *Calcinosis ; Humans ; *Mesothelioma ; *Pathology ; *Pleura ; *Pleural Diseases ; *Radiography, Thoracic ; }, } @article {pmid14282524, year = {1965}, author = {EISENSTADT, HB}, title = {BENIGN ASBESTOS PLEURISY.}, journal = {JAMA}, volume = {192}, number = {}, pages = {419-421}, doi = {10.1001/jama.1965.03080180077029}, pmid = {14282524}, issn = {0098-7484}, mesh = {*Asbestos ; *Asbestosis ; *Diagnosis, Differential ; Humans ; *Mesothelioma ; *Occupational Diseases ; *Pleural Neoplasms ; *Pleurisy ; *Radiography, Thoracic ; }, } @article {pmid14248731, year = {1965}, author = {SELIKOFF, IJ and CHURG, J and HAMMOND, EC}, title = {RELATION BETWEEN EXPOSURE TO ASBESTOS AND MESOTHELIOMA.}, journal = {The New England journal of medicine}, volume = {272}, number = {}, pages = {560-565}, doi = {10.1056/NEJM196503182721104}, pmid = {14248731}, issn = {0028-4793}, mesh = {*Asbestos ; *Asbestosis ; *Carcinogens ; *Carcinoma, Bronchogenic ; *Gastrointestinal Neoplasms ; Humans ; *Lung Neoplasms ; *Mesothelioma ; Neoplasms/*diagnosis/*epidemiology/*etiology ; *Peritoneal Neoplasms ; }, } @article {pmid14237901, year = {1965}, author = {ELMES, PC and MCCAUGHEY, WT and WADE, OL}, title = {DIFFUSE MESOTHELIOMA OF THE PLEURA AND ASBESTOS.}, journal = {British medical journal}, volume = {1}, number = {5431}, pages = {350-353}, pmid = {14237901}, issn = {0007-1447}, mesh = {*Asbestos ; *Asbestosis ; Humans ; Ireland ; *Mesothelioma ; Neoplasms/*epidemiology/*etiology ; *Occupational Diseases ; *Pathology ; *Pleura ; *Pleural Neoplasms ; *Sarcoma ; }, } @article {pmid14249377, year = {1965}, author = {SMITH, WE and MILLER, L and CHURG, J and SELIKOFF, IJ}, title = {MESOTHELIOMAS IN HAMSTERS FOLLOWING INTRAPLEURAL INJECTION OF ASBESTOS.}, journal = {Journal of the Mount Sinai Hospital, New York}, volume = {32}, number = {}, pages = {1-8}, pmid = {14249377}, issn = {0099-9695}, mesh = {Animals ; *Asbestos ; *Asbestosis ; Cricetinae ; *Mesothelioma ; *Neoplasms ; *Neoplasms, Experimental ; *Pathology ; *Pleural Neoplasms ; *Research ; }, } @article {pmid14253230, year = {1964}, author = {ELWOOD, PC and COCHRANE, AL and BENJAMIN, IT and SEYS-PROSSER, D}, title = {A FOLLOW-UP STUDY OF WORKERS FROM AN ASBESTOS FACTORY.}, journal = {British journal of industrial medicine}, volume = {21}, number = {4}, pages = {304-307}, pmid = {14253230}, issn = {0007-1072}, mesh = {*Abdominal Neoplasms ; *Asbestos ; *Asbestosis ; *Bronchial Neoplasms ; Follow-Up Studies ; Humans ; *Lung Neoplasms ; *Occupational Diseases ; *Pleural Neoplasms ; *Statistics as Topic ; *Toxicology ; }, abstract = {Associations between exposure to asbestos and carcinoma of the lung, diffuse mesothelioma of the pleura, and diffuse abdominal tumours have been demonstrated. Only by an epidemiological approach can the total risks of exposure to asbestos be estimated, and such a study is reported here. This suggests that white asbestos (chrysotile) may not be a serious hazard as far as mesothelioma or abdominal tumours are concerned, though there is some evidence of an excess in the number of deaths from carcinoma of the lung and bronchus.}, } @article {pmid14150909, year = {1964}, author = {OWEN, WG}, title = {DIFFUSE MESOTHELIOMA AND EXPOSURE TO ASBESTOS DUST IN THE MERSEYSIDE AREA.}, journal = {British medical journal}, volume = {2}, number = {5403}, pages = {214-218}, pmid = {14150909}, issn = {0007-1447}, mesh = {*Asbestos ; *Asbestosis ; *Carcinogens ; *Dust ; England ; *Geriatrics ; Humans ; *Lung Neoplasms ; *Mesothelioma ; Middle Aged ; Neoplasms/*epidemiology ; *Occupational Diseases ; *Pathology ; *Peritoneal Neoplasms ; *Pleural Neoplasms ; *Toxicology ; }, } @article {pmid14150908, year = {1964}, author = {FOWLER, PB and SLOPER, JC and WARNER, EC}, title = {EXPOSURE TO ASBESTOS AND MESOTHELIOMA OF THE PLEURA.}, journal = {British medical journal}, volume = {2}, number = {5403}, pages = {211-213}, pmid = {14150908}, issn = {0007-1447}, mesh = {*Asbestos ; *Asbestosis ; *Carcinogens ; *Geriatrics ; Humans ; *Mesothelioma ; *Microscopy ; Neoplasms/*diagnosis ; *Occupational Diseases ; *Pathology ; *Peritoneal Neoplasms ; *Pleura ; *Pleural Neoplasms ; *Radiography, Thoracic ; *Toxicology ; }, } @article {pmid14143506, year = {1964}, author = {HOURIHANE, DO}, title = {THE PATHOLOGY OF MESOTHELIOMATA AND AN ANALYSIS OF THEIR ASSOCIATION WITH ASBESTOS EXPOSURE.}, journal = {Thorax}, volume = {19}, number = {3}, pages = {268-278}, pmid = {14143506}, issn = {0040-6376}, mesh = {*Asbestos ; *Geriatrics ; *Mesothelioma ; *Neoplasm Metastasis ; Neoplasms/*epidemiology ; *Pathology ; *Peritoneal Neoplasms ; *Pleural Neoplasms ; Prognosis ; *Sarcoma ; *Serous Membrane ; *Silicon Dioxide ; United Kingdom ; }, } @article {pmid14107207, year = {1964}, author = {SELIKOFF, IJ and CHURG, J and HAMMOND, EC}, title = {ASBESTOS EXPOSURE AND NEOPLASIA.}, journal = {JAMA}, volume = {188}, number = {}, pages = {22-26}, doi = {10.1001/jama.1964.03060270028006}, pmid = {14107207}, issn = {0098-7484}, mesh = {*Asbestos ; *Asbestosis ; *Colonic Neoplasms ; *Geriatrics ; Humans ; *Lung Neoplasms ; *Mesothelioma ; Middle Aged ; *Minerals ; *Mortality ; Neoplasms/*epidemiology/*etiology ; New Jersey ; New York ; *Occupational Diseases ; *Pleural Neoplasms ; *Rectal Neoplasms ; *Smoking ; *Stomach Neoplasms ; }, } @article {pmid13981238, year = {1963}, author = {THOMSON, JG}, title = {Exposure to asbestos dust and diffuse pleural mesotheliomas.}, journal = {British medical journal}, volume = {1}, number = {5323}, pages = {123}, pmid = {13981238}, issn = {0007-1447}, mesh = {*Asbestos ; *Asbestosis ; *Dust ; Humans ; *Lung Neoplasms ; *Mesothelioma ; Mesothelioma, Malignant ; *Pleural Neoplasms ; }, } @article {pmid13932248, year = {1962}, author = {MCNULTY, JC}, title = {Malignant pleural mesothelioma in an asbestos worker.}, journal = {The Medical journal of Australia}, volume = {49(2)}, number = {}, pages = {953-954}, doi = {10.5694/j.1326-5377.1962.tb24396.x}, pmid = {13932248}, issn = {0025-729X}, mesh = {*Asbestos ; *Asbestosis ; Humans ; *Lung Neoplasms ; *Mesothelioma ; Mesothelioma, Malignant ; *Pleural Neoplasms ; }, } @article {pmid13782506, year = {1960}, author = {WAGNER, JC and SLEGGS, CA and MARCHAND, P}, title = {Diffuse pleural mesothelioma and asbestos exposure in the North Western Cape Province.}, journal = {British journal of industrial medicine}, volume = {17}, number = {4}, pages = {260-271}, pmid = {13782506}, issn = {0007-1072}, mesh = {*Asbestos ; *Asbestosis ; Humans ; *Lung Neoplasms ; *Medical Records ; *Mesothelioma ; Mesothelioma, Malignant ; *Neoplasms ; *Pleura ; *Pleural Neoplasms ; }, abstract = {Primary malignant tumours of the pleura are uncommon. Thirty-three cases (22 males, 11 females, ages 31 to 68) of diffuse pleural mesothelioma are described; all but one have a probable exposure to crocidolite asbestos (Cape blue). In a majority this exposure was in the Asbestos Hills which lie to the west of Kimberley in the north west of Cape Province. The tumour is rarely seen elsewhere in South Africa.}, } @article {pmid12891740, year = {2003}, author = {Novakova, K}, title = {[Unclear ascites].}, journal = {Praxis}, volume = {92}, number = {27-28}, pages = {1229-1231}, doi = {10.1024/0369-8394.92.27.1229}, pmid = {12891740}, issn = {1661-8157}, mesh = {Adult ; Asbestos/adverse effects ; Ascites/diagnosis/diagnostic imaging/*etiology ; Diagnosis, Differential ; Environmental Exposure/adverse effects ; Follow-Up Studies ; Humans ; Male ; Mesothelioma/complications/*diagnosis/etiology/therapy ; Palliative Care ; Peritoneal Neoplasms/complications/*diagnosis/etiology/therapy ; Time Factors ; Ultrasonography ; }, } @article {pmid12890657, year = {2003}, author = {Burdorf, A and Dahhan, M and Swuste, P}, title = {Occupational characteristics of cases with asbestos-related diseases in The Netherlands.}, journal = {The Annals of occupational hygiene}, volume = {47}, number = {6}, pages = {485-492}, doi = {10.1093/annhyg/meg062}, pmid = {12890657}, issn = {0003-4878}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Asbestosis/epidemiology/etiology ; Humans ; Mesothelioma/epidemiology/*etiology ; Middle Aged ; Netherlands/epidemiology ; Occupational Diseases/epidemiology/*etiology ; }, abstract = {OBJECTIVE: To describe the occupational background of cases with an asbestos-related disease and to present overall mesothelioma risks across industries with historical exposure to asbestos.

METHODS: For the period 1990-2000, cases were collected from records held by two law firms. Information on jobs held, previous employers, activities performed and specific products used were obtained from patients themselves or next of kin. Branches of industry and occupations were coded and the likelihood of asbestos exposure was assessed. For each branch of industry, the overall risk of mesothelioma was calculated from the ratio of the observed number of mesothelioma cases and the cumulative population-at-risk in the period 1947-1960. In order to compare mesothelioma risks across different industries, risk ratios were calculated for the primary asbestos industry and asbestos user industries relative to all other branches of industry.

RESULTS: In total, 710 mesotheliomas and 86 asbestosis cases were available. The average latency period was approximately 40 yr and the average duration of exposure was 22 yr. Ship building and maintenance contributed the largest number of cases (27%), followed by the construction industry (14%), the insulation industry (12%), and the navy and army, primarily related to ship building and maintenance (5%). In the insulation industry, the overall risk of mesothelioma was 5 out of 100 workers, and in the ship building industry, 1 out of 100 workers. The construction industry had an overall risk comparable with many other asbestos-using industries (7 per 10,000 workers), but due to its size claimed many mesothelioma cases.

CONCLUSION: The majority of cases with asbestos-related diseases had experienced their first asbestos exposure prior to 1960. For cases with first asbestos exposure after 1960, a shift was observed from the primary asbestos industry towards asbestos-using industries, such as construction, petroleum refining, and train building and maintenance. Due to the long latency period, asbestos exposure from 1960 to 1980 will cause a considerable number of mesothelioma cases in the next two decades.}, } @article {pmid12854383, year = {2003}, author = {Chan, K and Tan, KL and Lee, HS and Eng, P}, title = {Malignant mesothelioma: experience at the Singapore General Hospital.}, journal = {Annals of the Academy of Medicine, Singapore}, volume = {32}, number = {3}, pages = {388-391}, pmid = {12854383}, issn = {0304-4602}, mesh = {Aged ; Asbestos/*adverse effects ; Female ; Humans ; Male ; *Mesothelioma/diagnosis/etiology ; Middle Aged ; *Occupational Diseases/diagnosis/etiology ; *Peritoneal Neoplasms/diagnosis/etiology ; *Pleural Neoplasms/diagnosis/etiology ; Singapore ; }, abstract = {INTRODUCTION: Malignant mesothelioma is a rare occupational disease in Singapore. There have been few reports of this condition in Singapore. We aim to describe the clinical characteristics, management and outcomes in a case series of 16 patients diagnosed in a teaching hospital in Singapore.

MATERIALS AND METHODS: A chart review of all cases of malignant mesothelioma diagnosed in our institution during the period 1996 to 2001 was conducted, with particular attention to the occupational history.

RESULTS: There were 16 patients (15 male patients) with a median age of 61.5 (range, 46 to 78) years. Thirteen patients had malignant pleural mesothelioma (MPM) and 3 patients had mesothelioma of the periotoneum. Eleven of the patients with MPM (84.6%) presented with a pleural effusion and only 2 patients (15.4%) had chest pain. Initial pleural fluid cytology and closed pleural biopsies were negative in all patients who presented with a pleural effusion. Thoracoscopy confirmed the histologic diagnosis and allowed simultaneous talc pleurodesis in 9 patients. All patients had documented asbestos exposure, of which 14 (87.5%) were confirmed to be occupationally related. The median time from first exposure to symptoms was 33.5 (range, 16 to 53) years. The median survival was 6 months. Most of the patients (75%) received best supportive care alone.

CONCLUSIONS: In our experience, malignant mesothelioma is an aggressive disease with a poor prognosis. It is strongly associated with asbestos exposure. Thoracoscopy is an invaluable diagnostic modality in the evaluation of a patient with occupational asbestos exposure and an undiagnosed pleural effusion.}, } @article {pmid12854001, year = {2003}, author = {Svorcan, P and Djordjevic, J and Colic, N and Jojic, N and Vukcevic, V and Bojovic, S and Dapcevic, B}, title = {Primary malignant mesothelioma of the peritoneum.}, journal = {Romanian journal of gastroenterology}, volume = {12}, number = {2}, pages = {135-137}, pmid = {12854001}, issn = {1221-4167}, mesh = {Asbestos/adverse effects ; Fatal Outcome ; Humans ; Male ; Mesothelioma/*pathology ; Middle Aged ; Palliative Care ; Peritoneal Neoplasms/*pathology ; }, abstract = {Mesothelioma of the peritoneum represents an extremely rare malignancy of the abdominal cavity and forms about 10% of all mesotheliomas. The annual incidence of the tumor in the general population is 1-2 cases per million. The causative relationship between chronic exposure to asbestos and mesothelioma has been proved. Since the symptomatology of the tumor is usually not specific, the diagnosis is made in the advanced stages of the disease, which is the limiting factor for therapy. Most patients die within 2 years from the diagnosis. We report a case of a primary malignant mesothelioma of the peritoneum in a 60-year old male, who presented with three-month history of ascites, weakness and appetite loss. The patient gave the information that he had been living for 15 years in a loft which was insulated by material consisting of asbestos. After investigations, primary neoplasm of the peritoneum was suspected, which was confirmed by the biopsy and the morphopathological examination. Due to the advanced spread of the tumor and the poor general condition, the patient underwent palliative therapy. The patient died 3 months after the diagnosis. Epidemiological data for chronic exposure to asbestos have to be considered as the etiological factor of disease in this particular patient.}, } @article {pmid12852202, year = {2003}, author = {Rapisarda, V and Amati, M and Coloccini, S and Bolognini, L and Gobbi, L and Duscio, D}, title = {[The in vitro release of hydroxyl radicals from dust containing fluoro-edenite fibers identified in the volcanic rocks of Biancavilla (eastern Sicily)].}, journal = {La Medicina del lavoro}, volume = {94}, number = {2}, pages = {200-206}, pmid = {12852202}, issn = {0025-7818}, mesh = {Asbestos, Crocidolite/chemistry ; Ascorbic Acid/pharmacology ; Construction Materials/*adverse effects/analysis ; Deferoxamine/pharmacology ; Deoxyribose/analysis ; Dust/*analysis ; Fluorides/*chemistry ; Free Radical Scavengers/pharmacology ; Humans ; Hydrogen Peroxide/pharmacology ; Hydroxyl Radical/*analysis ; In Vitro Techniques ; Iron ; Iron Chelating Agents/pharmacology ; Mesothelioma/epidemiology/etiology ; Mineral Fibers/adverse effects ; Minerals/*chemistry ; Pleural Neoplasms/epidemiology/etiology ; Sicily/epidemiology ; Soil/*analysis ; Thiourea/*analogs & derivatives/pharmacology ; Volcanic Eruptions ; }, abstract = {BACKGROUND: Epidemiological studies revealed an unusually high incidence of malignant pleural mesothelioma in Biancavilla, a town in eastern Sicily located in a volcanic area. In the absence of occupational risk factors connected with asbestos inhalation, a nearby stone quarry, which has long been providing most of the local building materials (e.g. plaster), was suspected to be the source of mineral fibres. These fibres had never been studied before and were identified as fluoro-edenite.

OBJECTIVE: To investigate the ability of the fluoro-edenite fibres present in mineral dusts and house plaster to release hydroxyl radicals in vitro.

METHODS: After fibre characterisation and the determination of particulate specific surface, the ability of quarry rock dust and house plaster dust to generate hydroxyl radicals was measured in vitro using the deoxyribose degradation assay. Treatment with 1,3-dimethyl-2-thiourea (DMTU), a hydroxyl radical scavenger, or deferoxamine (DFX), an iron chelator, was performed to confirm hydroxyl radical production and study the role of iron. Crocidolite (UICC) was used as positive control.

RESULTS: The rocks were found to contain fibrous amphiboles, identified as fluoro-edenite, which are chemically similar to tremolite. All samples generated hydroxyl radicals, with rocks yielding consistently higher values than plaster. Treatment of the dusts with DMTU or DFX significantly reduced hydroxyl radical production by both samples. The type of biological reactivity observed with these fluoro-edenite fibres resembled that of asbestos fibres.

CONCLUSIONS: The hydroxyl radicals generated by asbestos fibres have long been known to mediate inflammatory fibrosis of the lung and DNA damage that may ultimately result in lung carcinoma and mesothelioma.}, } @article {pmid12848243, year = {2003}, author = {Pinheiro, GA and Antão, VC and Monteiro, MM and Capelozzi, VL and Terra-Filho, M}, title = {Mortality from pleural mesothelioma in Rio de Janeiro, Brazil, 1979-2000: estimation from death certificates, hospital records, and histopathologic assessments.}, journal = {International journal of occupational and environmental health}, volume = {9}, number = {2}, pages = {147-152}, doi = {10.1179/oeh.2003.9.2.147}, pmid = {12848243}, issn = {1077-3525}, mesh = {Asbestos/*adverse effects ; Brazil/epidemiology ; Death Certificates ; Female ; Humans ; International Classification of Diseases ; Male ; Medical Records ; Mesothelioma/chemically induced/classification/*mortality/pathology ; Pleural Neoplasms/chemically induced/classification/*mortality/pathology ; Predictive Value of Tests ; Reproducibility of Results ; }, abstract = {To obtain information about the occurrence of pleural mesothelioma on a population basis in Brazil, mortality related to pleural tumors in the State of Rio de Janeiro during 1979-2000 was examined. Death certificates with pleural tumors as the main cause of death and hospital records were analyzed, together with histopathologic material, which was reevaluated. Of 217 death certificates coded as pleural tumors, 34.1% were considered wrongly coded. Results after reclassification were: definite mesothelioma = 45 cases; probable = 7; possible = 31; inconclusive = 65; other tumors = 11. Thus, the number of mesotheliomas in Rio de Janeiro in 1979-2000 is estimated to have been 83. The analysis also suggests a problem with mortality codification in the State.}, } @article {pmid12848020, year = {2003}, author = {Amendola, P and Belli, S and Binazzi, A and Cavalleri, A and Comba, P and Mastrantonio, M and Trinca, S}, title = {[Mortality from malignant pleural neoplasms in Broni (Pavia), 1980-1997].}, journal = {Epidemiologia e prevenzione}, volume = {27}, number = {2}, pages = {86-90}, pmid = {12848020}, issn = {1120-9763}, mesh = {Adolescent ; Adult ; Age Distribution ; Aged ; Catchment Area, Health ; Child ; Child, Preschool ; Female ; Humans ; Incidence ; Infant ; Infant, Newborn ; Italy/epidemiology ; Male ; Middle Aged ; Pleural Neoplasms/*mortality ; Survival Rate ; }, abstract = {Mortality for malignant pleural neoplasms (1980-97) was studied in Broni (Pavia) and in the surrounding area in order to update previous studies indicating a high incidence of pleural mesothelioma, due to the presence of an asbestos-cement factory. Observed mortality for pleural neoplasms was compared to expected figures derived from mortality rates of the population resident in Province of Pavia. A significant increase was found in Broni (SMR 825, CI 95%: 604-1, 100, 46 observed). An increased risk of death from malignant pleural neoplasms was evident in both genders, especially in the most recent years, and in younger age groups; this increase in pleural neoplasm mortality also involves some neighbouring municipalities.}, } @article {pmid12839939, year = {2003}, author = {Ramos-Nino, ME and Scapoli, L and Martinelli, M and Land, S and Mossman, BT}, title = {Microarray analysis and RNA silencing link fra-1 to cd44 and c-met expression in mesothelioma.}, journal = {Cancer research}, volume = {63}, number = {13}, pages = {3539-3545}, pmid = {12839939}, issn = {0008-5472}, support = {ES/HL09213/ES/NIEHS NIH HHS/United States ; P01 HL67004/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Asbestos, Crocidolite/toxicity ; Hyaluronan Receptors/*genetics ; Mesothelioma/chemically induced/*genetics ; Neoplasms, Experimental/chemically induced/genetics ; *Oligonucleotide Array Sequence Analysis ; Proto-Oncogene Mas ; Proto-Oncogene Proteins c-fos/*genetics ; Proto-Oncogene Proteins c-met/*genetics ; RNA Interference/*physiology ; Rats ; Rats, Inbred F344 ; }, abstract = {Malignant mesothelioma is a cancer with poor prognosis associated with exposures to asbestos. The mechanisms of asbestos-induced mesotheliomas are unclear, and studies are required to find diagnostic tools and therapies to improve the survival rates of patients. After oligonucleotide microarray analysis (Affymetrix array) of normal rat pleural mesothelial (RPM) cells, RPM cells exposed to crocidolite asbestos, and rat mesotheliomas, subsets of genes that changed in expression were categorized, including the highly up-regulated, early response proto-oncogene, fra-1. Increases in fra-1 in both rat and human mesotheliomas and a subset of genes common to both asbestos-exposed RPM cells and mesotheliomas that mimicked fra-1 patterns of expression were subsequently confirmed using real-time quantitative PCR. Using RNA interference technology, fra-1 gene silenced RPM cells were assayed by real-time quantitative PCR for the expression of possible fra-1-regulated genes. Results reveal that induction of cd44 and c-met is causally linked to fra-1 expression, connecting fra-1 with genes governing cell motility and invasion in mesothelioma. These studies suggest that inhibition of fra-1 signaling pathways may be a strategy for therapy of malignant mesothelioma.}, } @article {pmid12833842, year = {2003}, author = {Kanaji, N and Hiyama, J and Horita, N and Shiota, Y and Imai, S}, title = {[A case of benign asbestos pleural effusion suspected on thoracoscopic examination under local anesthesia].}, journal = {Nihon Kokyuki Gakkai zasshi = the journal of the Japanese Respiratory Society}, volume = {41}, number = {6}, pages = {382-385}, pmid = {12833842}, issn = {1343-3490}, mesh = {Aged ; Aged, 80 and over ; *Anesthesia, Local ; Asbestosis/*complications ; Diagnosis, Differential ; Humans ; Male ; Pleural Effusion/*diagnosis ; *Thoracoscopy ; }, abstract = {We report the case of a 92-year-old man with a 13-year history of occupational asbestos exposure who presented with a complaint of dyspnea. In September 2001, bilateral pleural effusions were revealed on chest radiography, and continued to progress despite treatment for heart failure. Chest CT revealed calcification of the pleura but no abnormal findings in the lung fields. Both pleural effusions were exudative and lymphocytes were the predominant cells contained in them. Antituberculous chemotherapy had no effect on the exudates. In March 2002, thoracoscopy was performed under local anesthesia (medical thoracoscopy). Plaque was recognized on the parietal pleura; however, the serosal surfaces of the parietal and visceral pleura were smooth, and no evidence of malignancy, especially malignant mesothelioma, was noted. The patient's condition was diagnosed as benign asbestos pleural effusions. Prednisolone was administered, and these effusions gradually decreased. Cases of benign asbestos pleural effusion occurring simultaneously with massive bilateral effusions are rare. Thoracoscopy aided in the differential diagnosis of this case.}, } @article {pmid12822141, year = {2003}, author = {Rice, C and Heineman, EF}, title = {Application of a method to evaluate the quality of work histories and document the exposure assessment process.}, journal = {American journal of industrial medicine}, volume = {44}, number = {1}, pages = {94-106}, doi = {10.1002/ajim.10231}, pmid = {12822141}, issn = {0271-3586}, mesh = {Case-Control Studies ; Data Interpretation, Statistical ; Databases, Factual/standards ; *Employment ; Female ; Forms and Records Control/*methods ; Humans ; Male ; Occupational Exposure/analysis/*statistics & numerical data ; Occupational Health/*statistics & numerical data ; Probability ; Quality Control ; Records/*standards ; United States ; }, abstract = {BACKGROUND: Review of work history records by industrial hygienists is an important component of many occupational epidemiologic studies. A number of factors may influence the hygienist, such as the quality of the data and his or her previous experience. As part of a case-control study of mesothelioma, a system was developed to capture data on several factors that can be considered in a review of work history information.

METHODS: The overall quality of the work history record was described by noting the completeness and the consistency of the information; for any potential exposures, the reviewer experience on which the decision was based and the relative quality of the information were categorized. Because of the potential for mesothelioma cases and their next-of-kin to have undergone rigorous questioning about previous asbestos exposure an evaluation of the knowledge of the respondent was included. The frequency and intensity of exposure were also evaluated.

RESULTS: Evaluation of 3,444 work records is described. The importance of data completeness in the overall evaluation of quality is shown; follow-up questions regarding specific work tasks provide information not elicited in the standard interview process. The use of the literature was an important resource to the reviewer. Asbestos was reported by the respondent as an exposure on 149 work records; of these, 111 (74%) were judged to represent an unusual level of knowledge for a next-of-kin respondent.

CONCLUSIONS: The approach presented allows capture of information about data quality and experience of the reviewer in an epidemiologic analysis. The ratings of frequency and intensity of exposure allow exploration of differences in exposure-response analyses using various exposure metrics.}, } @article {pmid12822137, year = {2003}, author = {Coggiola, M and Bosio, D and Pira, E and Piolatto, PG and La Vecchia, C and Negri, E and Michelazzi, M and Bacaloni, A}, title = {An update of a mortality study of talc miners and millers in Italy.}, journal = {American journal of industrial medicine}, volume = {44}, number = {1}, pages = {63-69}, doi = {10.1002/ajim.10240}, pmid = {12822137}, issn = {0271-3586}, mesh = {Asbestos/poisoning ; Cause of Death ; Cohort Studies ; Esophageal Neoplasms/chemically induced/*mortality ; Follow-Up Studies ; Humans ; Italy/epidemiology ; Male ; Mineral Fibers/poisoning ; *Mining ; Mouth Neoplasms/chemically induced/*mortality ; Occupational Exposure/*adverse effects ; Silicosis/etiology/*mortality ; Talc/*poisoning ; Time Factors ; }, abstract = {BACKGROUND: While talc containing asbestiform fibers is considered a human carcinogen, only limited animal and human data are available on non-asbestiform talc. To provide further evaluation on the issue, we updated the analysis of an Italian cohort of talc miners and millers in Val Chisone; talc found here is free from asbestiform fibers.

METHODS: The cohort was comprised of 1,795 men who had worked for at least 1 year in the mine and/or in the factory between 1946 and 1995. Vital status and death certificates were obtained from registration offices in the municipality of death or of birth. Employment, termination of employment, and detailed job history were obtained from personnel records at the plant.

RESULTS: No excess was found for total cancer mortality, nor mortality for lung cancer. No case of mesothelioma was reported. There was a significant excess mortality from non-neoplastic respiratory diseases (SMR 228.2, 95% CI 190.2-271.5). Mortality excess for non-neoplastic respiratory diseases was mainly due to silicosis.

CONCLUSIONS: This study provides additional support for an association between talc in mining and milling and non-neoplastic respiratory diseases, while showing no significant excess risk for lung cancer and mesothelioma. The results also provide additional information of interest to evaluate the potential association between silica and lung cancer.}, } @article {pmid12802287, year = {2003}, author = {Fleury-Feith, J and Lecomte, C and Renier, A and Matrat, M and Kheuang, L and Abramowski, V and Levy, F and Janin, A and Giovannini, M and Jaurand, MC}, title = {Hemizygosity of Nf2 is associated with increased susceptibility to asbestos-induced peritoneal tumours.}, journal = {Oncogene}, volume = {22}, number = {24}, pages = {3799-3805}, doi = {10.1038/sj.onc.1206593}, pmid = {12802287}, issn = {0950-9232}, mesh = {Animals ; Asbestos, Crocidolite/*toxicity ; *Genes, Neurofibromatosis 2 ; *Genetic Predisposition to Disease ; Mesothelioma/*genetics ; Mice ; Mice, Nude ; Peritoneal Neoplasms/*genetics/pathology ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {Biallelic NF2 gene inactivation is frequently found in human malignant mesothelioma. In order to assess whether NF2 hemizygosity may enhance susceptibility to asbestos fibres, we investigated the Nf2 status in mesothelioma developed in mice presenting a heterozygous mutation of the Nf2 gene (Nf2(KO3/+)), after intraperitoneal inoculation of crocidolite fibres. Asbestos-exposed Nf2(KO3/+) mice developed tumoural ascites and mesothelioma at a higher frequency than their wild-type (WT) counterparts (P&<0.05). Six out of seven mesothelioma cell lines established from neoplastic ascitic fluids of Nf2(KO3/+) mice exhibited loss of the WT Nf2 allele and no neurofibromatosis type 2 protein expression was found in these cells. The results show the importance of the NF2 gene in mesothelial oncogenesis, the potential association of asbestos exposure and tumour suppressor gene inactivation, and suggest that NF2 gene mutation may be a susceptibility factor to asbestos.}, } @article {pmid12795187, year = {2003}, author = {Kishimoto, T}, title = {[A case of triple malignancies (gastric cancer, lung cancer and malignant pleural mesothelioma) after asbestos exposure].}, journal = {Nihon Kokyuki Gakkai zasshi = the journal of the Japanese Respiratory Society}, volume = {41}, number = {4}, pages = {304-309}, pmid = {12795187}, issn = {1343-3490}, mesh = {Adenocarcinoma/*etiology/pathology ; Aged ; Asbestos/*adverse effects ; Carcinoma, Squamous Cell/*etiology/pathology ; Humans ; Lung Neoplasms/*etiology/pathology ; Male ; Mesothelioma/*etiology/pathology ; *Neoplasms, Multiple Primary/pathology ; *Occupational Exposure ; Pleural Neoplasms/*etiology/pathology ; Stomach Neoplasms/*etiology/pathology ; }, abstract = {This case study centers on a seventy-eight-year-old man with triple malignancies, namely, gastric cancer, lung cancer and malignant pleural mesothelioma, all of which developed at different times. The histological types were adenocarcinoma of the stomach, squamous cell carcinoma of the lung and sarcomatous malignant pleural mesothelioma. Gastric cancer was treated by endoscopic mucosal resection 2 years ago. The patient presented with a chief complaint of dyspnea, and right pleural effusion was found on chest radiography. The right-side effusion disappeared spontaneously, but a small mass on the left side was diagnosed as lung cancer, and so left inferior lobe resection was performed. Malignant pleural mesothelioma appeared after one year of pleural effusion and the patient died of mesothelioma one year after diagnosis. At autopsy, the gastric cancer and lung cancer had not relapsed and malignant pleural mesothelioma had metastasized to the lung, liver, adrenal gland and small intestine. He was a sailor by profession and it was obvious that he had been exposed to asbestos, because 538 asbestos bodies per 5 g of wet lung tissue were detected. His advanced age was one of the risk factors for the multiple malignancies, and the asbestos exposure was considered to have compounded these hazards to cause the triple malignancies. It is well known that lung cancer and malignant mesothelioma are induced by asbestos exposure, but multiple cancers including lung cancer and malignant mesothelioma are extremely rare.}, } @article {pmid12795087, year = {2003}, author = {Nishiwaki, Y}, title = {[Malignant pleural mesothelioma].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {30}, number = {5}, pages = {589-594}, pmid = {12795087}, issn = {0385-0684}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Cisplatin/administration & dosage ; Clinical Trials as Topic ; Combined Modality Therapy ; Deoxycytidine/administration & dosage/*analogs & derivatives ; Drug Administration Schedule ; Female ; Glutamates/administration & dosage ; Guanine/administration & dosage/*analogs & derivatives ; Humans ; Male ; *Mesothelioma/diagnosis/drug therapy/surgery ; Pemetrexed ; *Pleural Neoplasms/diagnosis/drug therapy/surgery ; Randomized Controlled Trials as Topic ; Gemcitabine ; }, abstract = {Malignant pleural mesothelioma (MPM) used to be a rare disease, but is recently increasing in incidence. Most MPMs were thought to have a causal relationship with asbestos exposure. However, a DNA sequence similar to simian virus 40 has been detected in MPM tumor cells, which suggests a role of viral infection in its etiology. MPM predominantly afflicts men over 60 years old, with a male to female ratio of 3 to 1. MPM is a challenging disease in all aspects, including diagnosis, staging and treatment. Its diagnosis requires a panel of immunohistochemical stains. Multimodal treatment including surgery has shown significant benefit in highly selected patients. Most cytotoxic drugs administered as a single agent have been evaluated, but none have consistently demonstrated response rates greater than 20%. The combination of gemcitabine plus cisplatin has become a standard regimen, although there has been significant variability in response rates between studies. The novel antifolates pemetrexed and raltitrexed are promising agents and undergoing 3 phase III studies. One of these studies is the largest trial ever conducted in MPM patients, which randomized 456 patients into cisplatin with or without pemetrexed groups. The median survival time was 12.1 months in the cisplatin with pemetrexed arm and 9.3 months in the cisplatin alone arm (p = 0.02). Another of these studies is currently being conducted to compare cisplatin with or without raltitrexed. The third study is comparing pemetrexed alone to supportive care. The results of these trials are expected to define the role of chemotherapy for patients with MPM.}, } @article {pmid12787316, year = {2003}, author = {Ishikawa, R and Kikuchi, E and Jin, M and Fujita, M and Itoh, T and Sawa, H and Nagashima, K}, title = {Desmoplastic malignant mesothelioma of the pleura: autopsy reveals asbestos exposure.}, journal = {Pathology international}, volume = {53}, number = {6}, pages = {401-406}, doi = {10.1046/j.1440-1827.2003.01488.x}, pmid = {12787316}, issn = {1320-5463}, mesh = {Aged ; Aged, 80 and over ; Asbestos, Crocidolite/*adverse effects/isolation & purification ; Bone Neoplasms/secondary ; Fatal Outcome ; Female ; Humans ; Keratins/metabolism ; Mesothelioma/*etiology/metabolism/*secondary ; Pleural Neoplasms/*etiology/metabolism/*pathology ; Radiography, Thoracic ; Vimentin/metabolism ; }, abstract = {Desmoplastic mesothelioma is a rare subtype of diffuse malignant mesothelioma, and is often difficult to distinguish from reactive pleural fibrosis because of associated extensive collagen fibrosis. An 82-year-old woman with a severe cough was revealed to have pleural effusion and diffuse pleural thickening on the right side. Antibiotics were ineffective, and a compression fracture of the ninth and tenth thoracic vertebral bodies was recognized on X-ray. Autopsy revealed a diffuse pleural thickening with hyalinized collagen tissue in the central part of the pleura. However, the peripheral part of the fibrous tissue was composed of spindle and polygonal cell proliferation that were immunohistochemically positive for antibodies against cytokeratin and vimentin. In addition, the ninth and tenth thoracic spines were infiltrated by similar cells. The condition was diagnosed as desmoplastic mesothelioma with bone metastases. Asbestos bodies were detected in the thickened pleura and fibrosed alveolar septa, and it was suggested retrospectively that the patient had been exposed to asbestos. Thus, autopsy analyses of fibrous pleurisy are necessary to detect a desmoplastic variant of mesothelioma of the pleura and its association with asbestos exposure.}, } @article {pmid12784152, year = {2003}, author = {Treasure, T and Swift, S and Tan, C}, title = {Radical surgery for mesothelioma: how can we obtain evidence?.}, journal = {World journal of surgery}, volume = {27}, number = {8}, pages = {891-894}, pmid = {12784152}, issn = {0364-2313}, mesh = {Evidence-Based Medicine ; Humans ; Mesothelioma/mortality/*surgery ; Pleural Neoplasms/mortality/*surgery ; Pneumonectomy/methods ; Treatment Outcome ; }, abstract = {Asbestos exposure in industry and construction sites in the 1960s and 1970s has left a legacy of mesothelioma, a diffuse pleural cancer, with a lag time of 40 to 50 years and due to peak around 2015 to 2020. Some surgeons believe that by radical surgery they can prolong life and relieve symptoms, but the evidence comes from very carefully selected series. How do surgeons respond to demand for evidence of benefit? In this article we explore how evidence for major surgical operations has been gained and how mesothelioma fits into this history.}, } @article {pmid12780437, year = {2003}, author = {Au, VW and Thomas, M}, title = {Radiological manifestations of malignant pleural mesothelioma.}, journal = {Australasian radiology}, volume = {47}, number = {2}, pages = {111-116}, doi = {10.1046/j.0004-8461.2003.01137.x}, pmid = {12780437}, issn = {0004-8461}, mesh = {Aged ; Asbestos/*adverse effects ; Disease Progression ; Humans ; Male ; Mesothelioma/*diagnostic imaging/etiology ; Pleural Neoplasms/*diagnostic imaging/etiology ; Prognosis ; Thoracoscopy ; Tomography, X-Ray Computed ; }, abstract = {Malignant pleural mesothelioma has had a rising incidence in Australia over the past 40 years. This pictorial essay gives a brief account of the condition, summarizes the various radiological manifestations and aims at increasing the awareness of a disease that is expected to reach its peak incidence in the early decades of the twenty-first century.}, } @article {pmid12768194, year = {2003}, author = {Cordier Kellerman, L and Valeyrie, L and Fernandez, N and Opolon, P and Sabourin, JC and Maubec, E and Le Roy, P and Kane, A and Legrand, A and Abina, MA and Descamps, V and Haddada, H}, title = {Regression of AK7 malignant mesothelioma established in immunocompetent mice following intratumoral gene transfer of interferon gamma.}, journal = {Cancer gene therapy}, volume = {10}, number = {6}, pages = {481-490}, doi = {10.1038/sj.cgt.7700594}, pmid = {12768194}, issn = {0929-1903}, support = {R01 ES 03189/ES/NIEHS NIH HHS/United States ; }, mesh = {Adenoviridae/genetics ; Animals ; Apoptosis ; Blotting, Western ; Caspase 3 ; Caspases/metabolism ; Cell Line, Tumor ; Cell Separation ; Cytokines/metabolism ; DNA, Complementary/metabolism ; Down-Regulation ; Female ; Flow Cytometry ; *Gene Transfer Techniques ; Genetic Therapy/*methods ; Immunohistochemistry ; Interferon-gamma/*genetics/metabolism ; Mesothelioma/metabolism/pathology/*therapy ; Mice ; Mice, Inbred C57BL ; Neoplasm Transplantation ; Phosphorylation ; Polymerase Chain Reaction ; RNA/metabolism ; T-Lymphocytes/metabolism ; Time Factors ; Transforming Growth Factor beta/metabolism ; Up-Regulation ; }, abstract = {Malignant mesothelioma (MM) is a lethal tumor linked with a prior exposure to asbestos in which limited progress has been made so far using conventional therapies. MM is an example of a "nonimmunogenic" tumor characterized by a fibrous stroma and an absence of infiltrating T lymphocytes. High levels of transforming growth factor-beta (TGF-beta) produced by mesothelioma cells have been related to the immune tolerance towards the tumor. In order to evaluate the effect of local delivery of cytokines such as interferon gamma (IFN-gamma) by gene transfer, we characterized and used a murine model, AK7, which appeared very similar to human mesothelioma. AK7 cells expressed low levels of major histocompatibility class I and class II antigens and secreted high levels of latent TGF-beta. The TGF-beta pathway in AK7 cells is operative but inefficient because endogenous TGF-beta is predominantly inactive. Treatment of pre-established AK7 tumors by direct intratumoral injection of an adenovirus vector expressing murine IFN-gamma, Ad.mIFN-gamma, led to significant tumor regression. Peripheral tumor infiltration by CD4+ and CD8+ T lymphocytes in the treated tumors appeared to be because of the induction of an immune response. Tumor relapse was observed, which could be due to local TGF-beta secretion by remaining tumor cells.}, } @article {pmid12765873, year = {2003}, author = {Butnor, KJ and Sporn, TA and Roggli, VL}, title = {Exposure to brake dust and malignant mesothelioma: a study of 10 cases with mineral fiber analyses.}, journal = {The Annals of occupational hygiene}, volume = {47}, number = {4}, pages = {325-330}, doi = {10.1093/annhyg/meg048}, pmid = {12765873}, issn = {0003-4878}, mesh = {Aged ; Air Pollutants, Occupational/adverse effects/*analysis ; Asbestos, Amphibole/adverse effects/*analysis ; *Automobiles ; *Dust ; Humans ; Male ; Mesothelioma/*etiology ; Microscopy, Electron ; Middle Aged ; Mineral Fibers/analysis ; Occupational Exposure/*adverse effects ; Peritoneal Neoplasms/etiology ; Pleural Neoplasms/etiology ; }, abstract = {OBJECTIVES: A large number of workers in the USA are exposed to chrysotile asbestos through brake repair, yet only a few cases of malignant mesothelioma (MM) have been described in this population. Epidemiologic and industrial hygiene studies have failed to demonstrate an increased risk of MM in brake workers. We present our experience of MM in individuals whose only known asbestos exposure was to brake dust and correlate these findings with lung asbestos fiber burdens.

METHODS: Consultation files of one of the authors were reviewed for cases of MM in which brake dust was the only known asbestos exposure. Lung fiber analyses were performed using scanning electron microscopy (SEM) in all cases for which formalin-fixed or paraffin-embedded lung tissue was available.

RESULTS: Ten cases of MM in brake dust-exposed individuals were males aged 51-73 yr. Nine cases arose in the pleura and one in the peritoneum. Although the median lung asbestos body count (19 AB/g) is at our upper limit of normal (range 0-20 AB/g), half of the cases had levels within our normal range. In every case with elevated asbestos fiber levels by SEM, excess commercial amphibole fibers were also detected. Elevated levels of chrysotile and non-commercial amphibole fibers were detected only in cases that also had increased commercial amphibole fibers.

CONCLUSIONS: Brake dust contains exceedingly low levels of respirable chrysotile, much of which consists of short fibers subject to rapid pulmonary clearance. Elevated lung levels of commercial amphiboles in some brake workers suggest that unrecognized exposure to these fibers plays a critical role in the development of MM.}, } @article {pmid12763219, year = {2003}, author = {Marinaccio, A and Nesti, M and , }, title = {Analysis of survival of mesothelioma cases in the Italian register (ReNaM).}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {39}, number = {9}, pages = {1290-1295}, doi = {10.1016/s0959-8049(03)00233-8}, pmid = {12763219}, issn = {0959-8049}, mesh = {Adult ; Age Distribution ; Aged ; Asbestos/adverse effects ; Environmental Exposure/adverse effects ; Female ; Heart Neoplasms/*mortality ; Humans ; Italy/epidemiology ; Male ; Mesothelioma/*mortality ; Middle Aged ; Occupational Exposure/adverse effects ; Pericardium ; Peritoneal Neoplasms/*mortality ; Pleural Neoplasms/*mortality ; Proportional Hazards Models ; Registries ; Risk Factors ; Sex Distribution ; Survival Analysis ; }, abstract = {The Italian National Mesothelioma Register (ReNaM) was set up at ISPESL (the National Institute for Occupational Safety and Prevention) in 1993. Five Italian regions (Piedmont, Liguria, Emilia-Romagna, Tuscany and Puglia, with a total of approximately 17500000 inhabitants) agreed to record mesothelioma cases according to guidelines established by ISPESL, to define exposure to asbestos and transmit the data to ISPESL. We describe an analysis of survival of 429 mesothelioma cases-392 pleural, 34 peritoneal and 3 in the pericardium-diagnosed during 1997, with variable follow-up from June 1999 to December 2001. The Kaplan-Meier method was used to estimate survival rates, the log rank non-parametric test and Cox proportional hazard model to assess the role of prognostic factors such as age, gender, morphology, level of diagnostic certainty and modality of exposure. Median survival was 275 days (95% confidence interval (CI) 241-309) for pleural mesotheliomas and 157 days (95% CI: 118-196) for peritoneal mesotheliomas. Survival after diagnosis of malignant pleural mesothelioma showed a statistically significant linear trend for age group at diagnosis, for males and females (P=0.006 and 0.008, respectively). The Cox proportional hazard model gave an adjusted relative risk (RR(adj)), for the fibrous histotype, of 2.96 (95% CI: 1.28-6.81; P=0.012) compared with cases with unspecified morphology; for epithelioid and biphasic morphologies, the risk was lower than unity. There was no significant difference in survival for cases with confirmed exposure (occupational, household or environmental) or without.}, } @article {pmid12757757, year = {2003}, author = {Shukla, A and Ramos-Nino, M and Mossman, B}, title = {Cell signaling and transcription factor activation by asbestos in lung injury and disease.}, journal = {The international journal of biochemistry & cell biology}, volume = {35}, number = {8}, pages = {1198-1209}, doi = {10.1016/s1357-2725(02)00315-1}, pmid = {12757757}, issn = {1357-2725}, mesh = {Animals ; Asbestos/chemistry/*toxicity ; Calcium/metabolism ; Humans ; Lung/*drug effects/metabolism ; Mesothelioma/etiology/metabolism ; Mitogen-Activated Protein Kinase Kinases/*metabolism ; Pleural Neoplasms/etiology/metabolism ; Pneumonia/etiology/metabolism ; Protein Kinase C/*metabolism ; Protein Serine-Threonine Kinases/*metabolism ; Signal Transduction ; Transcription Factor AP-1/*metabolism ; NF-kappaB-Inducing Kinase ; }, abstract = {Signaling pathways initiated at the external cell surface or within the cytoplasm regulate transactivation of transcription factors and gene expression that are causally related to a number of critical cellular outcomes including proliferation, apoptosis, cell survival, and production of inflammatory cytokines. Asbestos, a ubiquitous pathogenic group of mineral fibers, can stimulate gene expression in a variety of cell types in the lung via intracellular signaling pathways. These cell signaling cascades may be initiated through receptor-mediated events or integrins. Alternatively, they may be stimulated by oxidants generated both during phagocytosis of minerals and/or by redox reactions on the mineral surface. Once initiated, these pathways can lead to promotion of gene expression critical to cellular injury, proliferation and inflammation-events leading to the development of fibroproliferative diseases of the lung and pleura. The elucidation and relevance of critical signaling cascades to lung injury or repair following asbestos exposure could aid in developing strategies to prevent or treat asbestos-associated lung and pleural diseases.}, } @article {pmid12756890, year = {2003}, author = {Merler, E and Bizzotto, R and Calisti, R and Cavone, D and De Marzo, N and Gioffrè, F and Mabilia, T and Marcolina, D and Musti, M and Munafò, MG and Roberti, S and Zambon, P}, title = {Mesotheliomas among Italians, returned to the home country, who worked when migrant at a cement-asbestos factory in Switzerland.}, journal = {Sozial- und Praventivmedizin}, volume = {48}, number = {1}, pages = {65-69}, doi = {10.1007/s000380300007}, pmid = {12756890}, issn = {0303-8408}, mesh = {Adult ; Asbestos/*adverse effects ; Construction Materials/*adverse effects ; Cross-Sectional Studies ; Emigration and Immigration ; Female ; Humans ; Incidence ; *Industry ; Italy/ethnology ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Pleural Neoplasms/*epidemiology ; Risk Assessment/statistics & numerical data ; Switzerland ; Transients and Migrants/*statistics & numerical data ; Workers' Compensation/statistics & numerical data ; }, abstract = {OBJECTIVES: To report the occurrence of mesotheliomas in Italy among subjects who worked, when migrant, at a cement-asbestos factory in Niederurnen, Switzerland, and had resettled to the home country.

METHODS: Information about the disease and on the working history of subjects was collected by regional mesothelioma registries. Only cases diagnosed by means of histo-pathological examinations have been considered here.

RESULTS: 15 mesotheliomas (13 pleural, 2 perithoneal; 12 among males, 3 among females) have been identified among Italians, who had worked at the factory. None of them had other occupational exposure to asbestos. The majority was living in the Veneto Region (North East of Italy), and in Puglia (Southern Italy).

CONCLUSIONS: Exposure to asbestos at this factory has already caused an important number of occupational cancers among the employees, a large fraction being constituted of migrants. In order to avoid under-estimation of risks and to allow compensation, diseases which occur among foreign workers returned to their home country should be evaluated. Migration for work is at the genesis of asbestos-related mesotheliomas now occurring in Italy.}, } @article {pmid12744636, year = {2001}, author = {Kattan, J and Faraj, H and Ghosn, M and Chahine, G and Assaf, E and Abadjian, G and Khoury, F}, title = {[Mesothelioma--asbestos in Lebanon: a problem to be considered].}, journal = {Le Journal medical libanais. The Lebanese medical journal}, volume = {49}, number = {6}, pages = {333-337}, pmid = {12744636}, issn = {0023-9852}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestosis/*epidemiology ; Environmental Exposure/*adverse effects ; Female ; Humans ; Incidence ; Lebanon/epidemiology ; Male ; Mesothelioma/*epidemiology/therapy ; Middle Aged ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*epidemiology/therapy ; }, abstract = {To estimate the incidence of pleural mesothelioma and its relationship with the occupational and environmental exposure to asbestos in Chekka region. Between 1991 and 2000, 22 cases of malignant mesothelioma were diagnosed at Hôtel-Dieu de France Hospital. Eighteen cases were epidemiologically investigated. Fifteen among these 18 patients (83%) had a positive exposure history: exposure was occupational in 11 cases and environmental in 4 cases. The tumor was attributable to Eternit Company in 12 cases among the exposed 15 (80%). These 12 cases were secondary to occupational exposures in 8 and to environmental exposure in 4 cases. Mean latency period between exposition and diagnosis was 29 years. Fifteen patients died from the progression of their disease after a median survival of 8 months. The relationship between pleural mesothelioma and Eternit Company with the related occupational and environmental risk in Chekka region is obvious. The assessment of the incidence needs a national cancer registry. Despite the protective measures taken by the government since 1996, an increase in the incidence is suspected in the coming ten years because of the long latency period of the disease.}, } @article {pmid12733840, year = {2003}, author = {Ascoli, V and Carnovale-Scalzo, C and Nardi, F and Efrati, C and Menegozzo, M}, title = {A one-generation cluster of malignant mesothelioma within a family reveals exposure to asbestos-contaminated jute bags in Naples, Italy.}, journal = {European journal of epidemiology}, volume = {18}, number = {2}, pages = {171-174}, pmid = {12733840}, issn = {0393-2990}, mesh = {Adult ; Asbestos/*adverse effects ; Cluster Analysis ; *Environmental Exposure ; Female ; Humans ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology/etiology/*genetics ; Middle Aged ; Peritoneal Neoplasms/*epidemiology ; Pleural Neoplasms/*epidemiology ; }, abstract = {Substantial evidence supports the role of asbestos in malignant mesothelioma. Clustering for this malignancy among relatives not only suggests genetic susceptibility as a relevant component but also provides a clue to investigate non-occupational sources of exposure. We identified five cases of malignant mesothelioma within one family with exposure to asbestos experienced during childhood, as 'next door' residents of a workshop recycling asbestos-contaminated jute sacks in Naples, Italy. This cluster discloses the health risk in the reuse of bags that previously had contained asbestos. Furthermore, it emphasizes the role of asbestos in the genetic-environmental interaction issue of malignant mesothelioma.}, } @article {pmid12733090, year = {2003}, author = {Neuberger, M and Vutuc, C}, title = {Three decades of pleural cancer and mesothelioma registration in Austria where asbestos cement was invented.}, journal = {International archives of occupational and environmental health}, volume = {76}, number = {2}, pages = {161-166}, doi = {10.1007/s00420-002-0397-2}, pmid = {12733090}, issn = {0340-0131}, mesh = {Asbestos/adverse effects ; Austria/epidemiology ; Female ; Humans ; Incidence ; Male ; Mesothelioma/*epidemiology/mortality ; Occupational Diseases/*epidemiology/mortality ; Pleural Neoplasms/*epidemiology/mortality ; Registries ; }, abstract = {Recently, a new mesothelioma epidemic was predicted from observations made in Western Europe. From early observations in Austria the lower increase in cases of mesothelioma compared with neighbor countries had been related to different uses of asbestos. In order to test this hypothesis, incidence and mortality of pleural cancer [International Classification of Diseases (ICD)-8/9 163] were analyzed for three decades and supplemented by data from a cohort study in the factory that had been the largest consumer of asbestos imported to Austria and from all Austrian occupational diseases registered between 1990 and 2001. In men, mortality rates (based on 15 to 45 deaths/year) were lowest in 1980-1989, but similar in 1970-1979 and 1990-2001. No increase in younger-birth cohorts was detected. Incidence rates (based on 13 to 44 cases/year) increased (36%) non-significantly (P=0.14). In women, a significant decrease in mortality and incidence rates (P<0.01) was observed from 1970. Rates from work-related mesothelioma (based on only 0-7 men and 0-4 women/year) must be interpreted with caution. In the cohort of 2,816 asbestos cement workers 26 pleural mesotheliomas were registered from 1990 through mid-1999. Six of these cases (three male and three female) had not been registered as an occupational disease, but all of these cases had been encoded under ICD 163 in mortality statistics. One female cohort member registered as having asbestosis according to the death certificate had died from mesothelioma according to the statistics of occupational diseases. We conclude that no epidemic of mesothelioma due to past asbestos exposure is to be expected in Austria.}, } @article {pmid12731387, year = {2002}, author = {Radziszewski, AS and Skrok, L and Weryński, W and Grochowski, Z and Radziszewski, AB}, title = {[Mesothelioma as delayed consequence of asbestos pollution].}, journal = {Przeglad lekarski}, volume = {59}, number = {12}, pages = {1048-1051}, pmid = {12731387}, issn = {0033-2240}, mesh = {Aged ; Asbestos/*adverse effects ; Environmental Exposure/*adverse effects ; Fatal Outcome ; Female ; Humans ; Lung Neoplasms/*etiology/therapy ; Male ; Mesothelioma/*etiology/therapy ; Middle Aged ; Risk Factors ; Time Factors ; }, abstract = {Mesothelioma is a relatively rare cancer, who's course is dynamic and leads to cahexia and patient death. The relationship has been proven between its incidence and exposition to asbestos. We presented six cases of mesothelioma in patients without professional risk, which were hospitalized in the internal sections of Pulmonological wards. Unfortunately, administered treatment did not bring expected results.}, } @article {pmid12724555, year = {2003}, author = {Hilliard, AK and Lovett, JK and McGavin, CR}, title = {The rise and fall in incidence of malignant mesothelioma from a British Naval Dockyard, 1979-1999.}, journal = {Occupational medicine (Oxford, England)}, volume = {53}, number = {3}, pages = {209-212}, doi = {10.1093/occmed/kqg051}, pmid = {12724555}, issn = {0962-7480}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Carcinogens/*adverse effects ; England/epidemiology ; Female ; Humans ; Incidence ; Male ; Mesothelioma/*mortality/prevention & control ; Middle Aged ; Naval Medicine ; Occupational Diseases/etiology/*mortality ; Occupational Exposure/adverse effects ; Peritoneal Neoplasms/*mortality/prevention & control ; Pleural Neoplasms/*mortality/prevention & control ; Risk Factors ; }, abstract = {BACKGROUND: The incidence of malignant mesothelioma in Britain is predicted to rise over the next 15-25 years because of past failure to protect the workforce against inhalation of asbestos. In British Naval dockyards, alternative insulation materials and respiratory protection were introduced from the mid-1960s. Aims This study was carried out to investigate the effects of these control measures on mesothelioma deaths in dockyard workers.

METHODS: Cases of mesothelioma of the pleura and peritoneum between 1979 and 1999 in workers from the Devonport Naval Dockyard, south-west England, were sought from coroners' and medico-legal records.

RESULTS: Three hundred and one cases were identified, 7% peritoneal. The peak incidence occurred in 1991 with 25 cases per annum (quadratic model fit R(2) = 74.2%, P < 0.001) and we predict that by 2003 the incidence will fall to fewer than five cases per annum. The mean time between first exposure and presentation was 48.5 years [95% confidence interval (CI) = 47.3-49.8], but this was significantly shorter in the more heavily exposed trades, when compared with the less heavily exposed (42 years, 95% CI = 39.0-45.0, versus 49.5 years, 95% CI = 48.2-50.9). Those with higher exposure were also at significantly greater risk of peritoneal disease (P < 0.023, Fisher's exact test).

CONCLUSION: The reduction in incidence of mesothelioma is greater than can be accounted for by reduction in numbers of dockyard workers over the last 50 years. Changes in insulation materials and improved industrial hygiene measures introduced into the Devonport Dockyard from the mid-1960s have resulted in an earlier decline in the incidence of malignant mesothelioma than that predicted for the British workforce as a whole.}, } @article {pmid12711421, year = {2003}, author = {Harris, LV and Kahwa, IA}, title = {Asbestos: old foe in 21st century developing countries.}, journal = {The Science of the total environment}, volume = {307}, number = {1-3}, pages = {1-9}, doi = {10.1016/S0048-9697(02)00504-1}, pmid = {12711421}, issn = {0048-9697}, mesh = {Asbestos/*adverse effects ; Carcinogens/*adverse effects ; Cultural Characteristics ; *Developing Countries ; *Environmental Exposure ; Epidemiologic Studies ; Humans ; Industry ; *Occupational Exposure ; *Occupational Health ; Risk Factors ; }, abstract = {While use of asbestos materials in developed nations has been decreasing because of the harmful health effects of asbestos dust mining, processing and use of the ancient material in developing countries is increasing. The regulatory mechanism for use, handling and disposal of asbestos and associated waste in developing countries are weak and information on asbestos-related diseases is scanty but emerging. We identify lack of epidemiological data on asbestos health effects as a major gap to be bridged in the promotion of occupational and environmental health in developing countries. Without data on local situations, diseases such as asbestosis and mesothelioma remain too obscure to assist the campaign for appropriate regulation of asbestos usage or attracting attention to abominable industrial practices generally.}, } @article {pmid12708722, year = {2003}, author = {Rafnsson, V and Sulem, P}, title = {Cancer incidence among marine engineers, a population-based study (Iceland).}, journal = {Cancer causes & control : CCC}, volume = {14}, number = {1}, pages = {29-35}, doi = {10.1023/a:1022505308892}, pmid = {12708722}, issn = {0957-5243}, mesh = {Adult ; Cohort Studies ; *Engineering ; Humans ; Iceland/epidemiology ; Incidence ; Male ; Middle Aged ; Neoplasms/*epidemiology ; Occupational Diseases/*epidemiology ; Population Surveillance ; Smoking/adverse effects ; }, abstract = {OBJECTIVES: Marine engineers are in their occupation exposed to different chemicals, organic solvents, exhaust gases, oils, and petroleum products, and were formerly exposed to asbestos. The aim was to study the cancer pattern, with particular attention to lung and bladder cancer, in an Icelandic cohort of marine engineers, indirectly controlling for their smoking habits.

METHODS: A cohort of 6603 male marine engineers was followed up from 1955 to 1998, a total of 167,715 person-years. The cohort was record linked by the engineers' personal identification numbers to population-based registers containing the vital and emigration status and cancer diagnosis. Standardized incidence ratios (SIRs) were calculated for all cancers and different cancer sites in relation to different lag time and year of graduation. Information on smoking habits was obtained by administering a questionnaire to a sample of the cohort (n = 1,501).

RESULTS: In the total cohort 810 cancers were observed, whereas 794 were expected (SIR 1.0, 95% CI 1.0-1.1), and significantly increased risk of stomach cancer (SIR 1.3, 95% CI 1.0-1.5) and lung cancer (SIR 1.2, 95% CI 1.0-1.5) was found. Increased risk of all cancers (SIR 1.2, 95% CI 1.1-1.3), stomach cancer (SIR 1.5, 95% CI 1.1-1.9), lung cancer (SIR 1.4, 95% CI 1.2-1.8), pleural mesothelioma (SIR 4.8, 95% CI 1.3-12.3), and urinary bladder cancer (SIR 1.3, 95% CI 1.0-1.8) were observed when a 40-year lag time was applied. The engineers' smoking habits were similar to those in a sample of the general population. The predictive value for lung cancer was 1.03.

CONCLUSIONS: The increased risk for mesothelioma is possibly attributable to the previous asbestos exposure. The excess of lung cancer could also be related to asbestos exposure. The high incidence of stomach cancer, lung cancer, and bladder cancer may be related to exposure to chemical risk factors, such as oils and petroleum products, as confounding due to smoking seems to be ruled out. In the light of the limited exposure information in the present study the importance of the different occupational exposures needs to be evaluated in further studies.}, } @article {pmid12708150, year = {2003}, author = {Hemminki, K and Li, X}, title = {Time trends and occupational risk factors for pleural mesothelioma in Sweden.}, journal = {Journal of occupational and environmental medicine}, volume = {45}, number = {4}, pages = {456-461}, doi = {10.1097/01.jom.0000058341.05741.7e}, pmid = {12708150}, issn = {1076-2752}, mesh = {Adult ; Female ; Humans ; Incidence ; Male ; Mesothelioma/*epidemiology ; Occupational Diseases/*epidemiology ; Pleural Neoplasms/*epidemiology ; Risk Factors ; Socioeconomic Factors ; Sweden/epidemiology ; }, abstract = {Epidemiologic data on pleural mesothelioma are scarce on regional and occupational time trends, which would monitor the effects of changes in exposure to asbestos. We aim to characterize time trends, regional, socioeconomic, and occupational risk factors for pleural mesothelioma in Sweden in the years from 1961 to 1998. The Swedish Family-Cancer Database was used to identify patients with pleural mesothelioma. Age-standardized incidence rates and standardized incidence ratio (SIR) were calculated for the population in the Database. A total of 1298 male and 233 female pleural mesotheliomas were retrieved. Age-standardized incidence of the disease was highest, and the trend increased in residents of large industrial and shipbuilding cities. In the last follow-up period, the male rate exceeded the female rate about 10-fold. Among male socioeconomic groups, manual workers showed the highest and ever-increasing SIR. No female socioeconomic group was at risk. For men, plumbers and seamen had the highest risk of 4.56 and 2.83, respectively, but the risks appeared to be decreasing for plumbers, whereas no clear trend was noted for seamen, probably because of indirect expose in ships. Farmers showed an SIR of 0.28, indicating that the population at large was at four times higher risk than farmers. The SIRs of many academic/college-educated groups were two to six times higher than those of farmers, suggesting indirect exposure to asbestos in these groups.}, } @article {pmid12708149, year = {2003}, author = {Hemminki, K and Li, X}, title = {Time trends and occupational risk factors for peritoneal mesothelioma in Sweden.}, journal = {Journal of occupational and environmental medicine}, volume = {45}, number = {4}, pages = {451-455}, doi = {10.1097/01.jom.0000052960.59271.d4}, pmid = {12708149}, issn = {1076-2752}, mesh = {Adolescent ; Adult ; Aged ; Child ; Female ; Humans ; Incidence ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Occupational Diseases/*epidemiology ; Peritoneal Neoplasms/*epidemiology ; Risk Factors ; Sweden/epidemiology ; }, abstract = {Epidemiologic data on peritoneal mesothelioma are scarce but exposure to asbestos is an identified risk factor. To characterize the disease, time trends, age-incidence relationships, and occupational risk factors for peritoneal mesothelioma were studied based on the Swedish Family-Database covering years 1961 to 1998. Peritoneal mesothelioma is a rare disease and only 96 male and 113 female cases were recorded during the 38-year period. Age-standardized incidence of the disease has increased for men until 1985 and leveled off thereafter. The incidence in women has been equally high but it has continued to increase toward the end of the follow-up period. The incidence was maximal at an age around 80 years for both genders. No female occupational or socioeconomic group was at risk. For men, 29% of the cases had typical asbestos related jobs with a SIR of 1.70. Bricklayers and plumbers had the highest risk of 7.22 and 5.12, respectively. Within limits of the sample size, no evidence was noted for risk from environmental exposures to asbestos because the risk of farmers and that of urban residents were not different.}, } @article {pmid12706492, year = {2003}, author = {Shukla, A and Gulumian, M and Hei, TK and Kamp, D and Rahman, Q and Mossman, BT}, title = {Multiple roles of oxidants in the pathogenesis of asbestos-induced diseases.}, journal = {Free radical biology & medicine}, volume = {34}, number = {9}, pages = {1117-1129}, doi = {10.1016/s0891-5849(03)00060-1}, pmid = {12706492}, issn = {0891-5849}, mesh = {Animals ; Asbestos/*toxicity ; Humans ; Inflammation/metabolism/pathology ; Lung/metabolism/pathology ; Lung Diseases/*chemically induced/*metabolism/pathology ; Oxidants/*metabolism ; Reactive Nitrogen Species/*metabolism ; Reactive Oxygen Species/*metabolism ; }, abstract = {Exposure to asbestos causes cellular damage, leading to asbestosis, bronchogenic carcinoma, and mesothelioma in humans. The pathogenesis of asbestos-related diseases is complicated and still poorly understood. Studies on animal models and cell cultures have indicated that asbestos fibers generate reactive oxygen and nitrogen species (ROS/RNS) and cause oxidation and/or nitrosylation of proteins and DNA. The ionic state of iron and its ability to be mobilized determine the oxidant-inducing potential of pathogenic iron-containing asbestos types. In addition to their capacity to damage macromolecules, oxidants play important roles in the initiation of numerous signal transduction pathways that are linked to apoptosis, inflammation, and proliferation. There is strong evidence supporting the premise that oxidants contribute to asbestos-induced lung injury; thus, strategies for reducing oxidant stress to pulmonary cells may attenuate the deleterious effects of asbestos.}, } @article {pmid12705942, year = {2003}, author = {Fach, E and Kristovich, R and Long, JF and Waldman, WJ and Dutta, PK and Williams, MV}, title = {The effect of iron on the biological activities of erionite and mordenite.}, journal = {Environment international}, volume = {29}, number = {4}, pages = {451-458}, doi = {10.1016/S0160-4120(02)00193-9}, pmid = {12705942}, issn = {0160-4120}, mesh = {Aluminum Silicates/*adverse effects/chemistry ; Animals ; CHO Cells ; Cricetinae ; *DNA Damage ; Dose-Response Relationship, Drug ; Drug Interactions ; Iron/adverse effects/chemistry/*pharmacokinetics ; Mutagenicity Tests ; Zeolites/*adverse effects/chemistry ; }, abstract = {Epidemiological data has demonstrated that environmental and/or occupational exposure to mineral particulates may result in the development of pulmonary fibrosis, bronchogenic carcinoma and malignant mesothelioma many years following exposure. It has been suggested that the genotoxic effects of fibrous particulates, such as asbestos, is due in part to the generation of reactive oxygen species (ROS) from iron associated with the particulates. However, the molecular mechanisms by which mineral particulates induce ROS that results in genotoxic damage remains unclear. The naturally occurring zeolites, erionite and mordenite share several physiochemical properties but they elicit very different biological responses, with erionite, a fibrous particulate, being highly toxic, and mordenite, a nonfibrous particulate, being relatively benign. We are using these natural zeolites as a model system to determine what physicochemical properties of these zeolites are responsible for their biological response(s) and to evaluate the parameters that influence these responses. The purpose of the present study was to determine the mutagenic potential of erionite and mordenite and to determine whether this mutagenic potential was modulated by iron. The results of this study using the Chinese hamster ovary cell line AS52 demonstrated that erionite was more cytotoxic than mordenite. However, the cytotoxicity of both zeolites was increased in the presence of physiological concentrations of ferrous chloride. Ferrous ions (5-20 microM) significantly (p<0.001) increased the cytotoxicity of mordenite, but only at the highest concentration (16 microg/cm(2)) of mordenite tested. Conversely, only the highest concentration (20 microM) of ferrous ion significantly (p<0.001) increased the cytotoxicity of erionite, but this enhanced cytotoxicity occurred over a wider concentration range (6-16 microg/cm(2)) of erionite. Mordenite was not mutagenic at any of the concentrations tested, and the mutagenic potential of mordenite was not enhanced by the addition of ferrous ion. Conversely, erionite was mutagenic in a dose-response manner at concentrations greater than 6 microg/cm(2) and the mutagenic potential of erionite was significantly enhanced by the addition of ferrous ions. These results suggest that while the cytotoxicity of mordenite and erionite may be related to the ability of these fibers to transport iron into a cell, the different coordination state of iron associated with the two fiber surfaces is critical for inducing genotoxic damage.}, } @article {pmid12704628, year = {2003}, author = {Greenberg, M}, title = {Biological effects of asbestos: New York Academy of Sciences 1964.}, journal = {American journal of industrial medicine}, volume = {43}, number = {5}, pages = {543-552}, doi = {10.1002/ajim.10192}, pmid = {12704628}, issn = {0271-3586}, mesh = {Academies and Institutes/history ; Asbestos/adverse effects/*history ; Congresses as Topic/history ; History, 20th Century ; Humans ; Lung Neoplasms/chemically induced/*history ; Mesothelioma/chemically induced/*history ; New York ; Occupational Exposure/adverse effects/history ; }, abstract = {BACKGROUND: In 1964, the New York Academy of Sciences held a conference on asbestos that was to promote the slow decline in the fortunes of asbestos. It brought together a Who's Who of international scientists who had conducted and reported on experimental and human studies of the effects of asbestos. Very little new data were presented at the conference, but by bringing together a compendium of knowledge of the adverse effects of asbestos, it served further notice to asbestos-using industry of the major public health problem that they had created. With the assistance of its employees and certain scientists, industry mounted public relations exercises to counter the adverse publicity of lung cancer and malignant mesothelioma. Attempts were made to minimize the impact of these diseases by suggesting that their alleged associations with asbestos were spurious, and by diversionary ad hominem attacks on Professor Irving J. Selikoff who had played an important role in the organization of the conference.

METHODS: Consideration of the contents of the meeting program, other previously published information and documents revealed through legal discovery by Chase Manhattan Bank provide the sources on which this paper is based.

CONCLUSIONS: Today, asbestos is no longer seen as a material indispensable on technical grounds and a mainstay of industry and the economy. Its progressive banning in developed countries may be seen as the consequence of the momentum initiated in New York in 1964.}, } @article {pmid12701534, year = {2002}, author = {Szeszenia-Dabrowska, N and Szubert, Z}, title = {[Prophylactic examinations of former workers of asbestos processing plants: the Amiantus project].}, journal = {Medycyna pracy}, volume = {53}, number = {6}, pages = {451-456}, pmid = {12701534}, issn = {0465-5893}, mesh = {Asbestosis/epidemiology/*prevention & control ; Environmental Monitoring ; Epidemiological Monitoring ; Health Plan Implementation ; Health Policy ; Humans ; Lung Neoplasms/etiology/prevention & control ; *Mass Screening/methods ; National Health Programs/*organization & administration ; Occupational Diseases/epidemiology/*prevention & control ; Occupational Exposure/*prevention & control/statistics & numerical data ; Occupational Health/*legislation & jurisprudence ; Poland/epidemiology ; Population Surveillance ; Public Health ; }, abstract = {Prophylactic examinations of the former workers of asbestos plants are performed by virtue of the Law of 19 June 1997 on a prohibition against the use of asbestos-containing products. Periodical examinations allow to detect pathological changes in the pre-symptomatic or early-symptomatic period, which permits to apply an appropriate treatment and slows down considerably the progress of morbid processes. The main objectives of the surveillance and coordination are as follows: (1) to assure good quality of prophylactic examinations through the uniform methods of medical examinations and the detection of pathology resulting from the exposure to asbestos dust, based on international criteria for diagnosing asbestos-related diseases (the Helsinki criteria, 1997); (2) to monitor the respiratory health effects among persons occupationally exposed to asbestos dust; and (3) to keep the database on persons examined and subjected to periodical prophylactic examinations throughout the country. The program of prophylactic examinations of persons occupationally exposed to asbestos dust includes mass screening. For the purpose of this program, a unified strategy of mass screening, including documentation (questionnaires on clinical, radiological and spirometric examinations) and instructions for persons responsible for performing these examinations has been worked out. Each center involved in the implementation of the program has been provided with binding criteria elaborated on the basis of the world standards (the Helsinki criteria, 1977) of clinical, radiological, spirometric and histological examinations aimed at detecting asbestos-related diseases: asbestosis, fibrous mesothelioma and lung cancer. The data obtained will serve as a basis for assessing the morbidity and incidence of asbestos-related diseases among persons occupationally exposed to asbestos dust in asbestos processing plants.}, } @article {pmid12701533, year = {2002}, author = {Marek, K}, title = {[Asbestos-related carcinogenic risk].}, journal = {Medycyna pracy}, volume = {53}, number = {6}, pages = {447-449}, pmid = {12701533}, issn = {0465-5893}, mesh = {Asbestos/*adverse effects ; Carcinogens/*adverse effects ; Humans ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Occupational Diseases/*etiology ; Occupational Exposure/*adverse effects ; Pleural Diseases/etiology ; Pleural Neoplasms/etiology ; Poland ; Pulmonary Fibrosis/etiology ; Risk Factors ; }, abstract = {Exposure to asbestos containing dust and its health effects are underestimated in many countries throughout the world, particularly in Poland. Asbestos has been proved to be carcinogenic to humans. The most specific health effect of asbestos exposure is pleural, pericardial and peritoneal mesothelioma. The relationship between asbestos exposure and primary lung cancer has been also documented. The association between pleural mesothelioma and asbestos exposure can be estimated by assessing the number of asbestos fiber in the lung tissue, or by checking the history of significant asbestos exposure. Minimum latency is 10 years, but in most cases it ranges between 20 and 40 years. Asbestos-related lung cancer occurs at varied frequency, depending on the country. The lung cancer risk is underestimated, but the frequency of its diagnosis is increasing owing to better detectability, despite the asbestos-use limitation. Lung cancer is distinctly more frequent in patients with asbestosis. In case of heavy occupational exposure, lung cancer can occur already after 1 year of work, but as mentioned earlier its minimum latency period is 10 years.}, } @article {pmid12695939, year = {2003}, author = {Meister, T and Birkfellner, T and Poremba, C and Becker, JC and Menzel, J and Domschke, W and Lerch, MM}, title = {Papillary mesothelioma of the peritoneum in the absence of asbestos exposure.}, journal = {Zeitschrift fur Gastroenterologie}, volume = {41}, number = {4}, pages = {329-332}, doi = {10.1055/s-2003-38637}, pmid = {12695939}, issn = {0044-2771}, mesh = {Asbestosis/*diagnosis/pathology ; Biomarkers, Tumor/analysis ; Biopsy ; Diagnosis, Differential ; Humans ; Laparoscopy ; Male ; Mesothelioma/*diagnosis/pathology ; Middle Aged ; Peritoneal Neoplasms/*diagnosis/pathology ; Peritoneum/pathology ; }, abstract = {BACKGROUND: Malignant mesothelioma of the peritoneum is a very rare neoplasm, commonly associated with asbestos exposure and often rapidly fatal. Well Differentiated Papillary Mesothelioma of the Peritoneum (WDPMP) is regarded as a less aggressive variety of the tumor. Progressive ascites is often the only clinical manifestation of the disease and differentiation of WDPMP from benign mesothelial hyperplasia or adenocarcinoma is difficult.

PATIENTS AND METHODS: Here we report the case of a 45-year-old patient who presented with ascites but without evidence of portal hypertension, liver disease or abdominal malignancy. On diagnostic laparoscopy small tumor nodules were found to cover the parietal peritoneum and the greater omentum and histopathologically corresponded to papillary mesothelial hyperplasia with minimal nuclear atypia. Histochemically biopsies were positive for Calretinin, Cytokeratins and Epithelial Membrane Antigen (EMA). Based on these findings the diagnosis of WDPMP was made and the patient was closely followed without primary cytostatic therapy.

CONCLUSIONS: Progressive ascites was the only clinical symptom in this patient, while liver disease, portal hypertension and gastrointestinal malignancies were ruled out by clinical, laboratory and imaging techniques. Laparoscopic biopsy revealed WDPMP to be the underlying disease. Immunocytochemistry is required to establish the diagnosis of this rare malignant disorder which is even more uncommon in the absence of a history of asbestos exposure. Due to the indolent course of WDPMP therapy should only be initiated when signs of rapid tumor progression become apparent.}, } @article {pmid12693287, year = {2003}, author = {Gorini, G}, title = {[Malignant mesothelioma in Tuscany].}, journal = {Epidemiologia e prevenzione}, volume = {27}, number = {1}, pages = {59}, pmid = {12693287}, issn = {1120-9763}, mesh = {Asbestos/adverse effects ; Female ; Humans ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology/etiology ; Pleural Neoplasms/*epidemiology/etiology ; }, } @article {pmid12673499, year = {2003}, author = {Müller, KM and Dernbach, AB and Neumann, V}, title = {[Mesotheliomas in academics. German mesothelioma register in Bochum].}, journal = {Der Pathologe}, volume = {24}, number = {2}, pages = {109-113}, doi = {10.1007/s00292-002-0561-1}, pmid = {12673499}, issn = {0172-8113}, mesh = {Faculty ; Geography ; Germany/epidemiology ; Humans ; Mesothelioma/classification/*epidemiology/*pathology ; Prevalence ; Registries ; Universities ; }, abstract = {Of a total of 4455 persons with mesotheliomas listed in the German register of mesotheliomas, 72 patients have an academic education in whom exposure to asbestos would not necessarily be assumed at first. Only one patient in this group was female. The tumors were located in the pleura in 94% (n=68) and in the peritoneum in 6% (n=4). The mean age at the time of diagnosis was 59.1 years. The mean survival time was 10.2 months. The epitheloid subtype predominated (57.7%, n=41) followed by the biphasic subtype (33.8%, n=24). Development of the sarcomatoid subtype was the least common (8.5%, n=6). Lung dust analysis provided proof for elevated pulmonary asbestos load in 78.2% of the patients. Work-related or non-work-related exposure to asbestos was cited or at least suspected by 68% (n=49) of the patients. The mean latency period was 36.8 years. Thus, in those patients with an academic career the majority of mesotheliomas can be considered associated with asbestos.}, } @article {pmid12643444, year = {2002}, author = {Dopp, E and Poser, I and Papp, T}, title = {Interphase fish analysis of cell cycle genes in asbestos-treated human mesothelial cells (HMC), SV40-transformed HMC (MeT-5A) and mesothelioma cells (COLO).}, journal = {Cellular and molecular biology (Noisy-le-Grand, France)}, volume = {48 Online Pub}, number = {}, pages = {OL271-7}, pmid = {12643444}, issn = {0145-5680}, mesh = {Asbestos/*toxicity ; Cell Culture Techniques/methods ; Cell Cycle/drug effects/*genetics ; *Cell Transformation, Neoplastic ; Cyclin D1/*genetics ; Epithelium/*drug effects/pathology ; Genes, Tumor Suppressor/drug effects ; Humans ; In Situ Hybridization, Fluorescence ; Mesothelioma/*genetics/pathology ; Nucleic Acid Hybridization ; Point Mutation ; Sequence Deletion ; Simian virus 40/*genetics ; Tumor Cells, Cultured ; }, abstract = {The epidemiologic association between asbestos exposure and human malignant mesothelioma is well established. However, the molecular mechanisms linking asbestos exposure of humans and the subsequent mesothelioma formation is not well understood. The most frequent genetic changes found so far in human malignant mesothelioma (HMM) are deletions and point mutations in the tumor suppressor genes p16INK4a and NF2. Whereas homozygous deletions appear to be the predominant mechanism leading to p16/CDKN2A inactivation, inactivating point mutations coupled with allelic loss mainly occur at the NF2 locus. In the present study, asbestos-treated human mesothelial cells (HMC), SV40-transformed human mesothelial cells (MeT-5A) and a human mesothelioma cell line (COLO) were investigated for genetic changes of cell cycle genes (cyclin D1, p16INK4a, RB1, CDK2) using multicolor fluorescence in situ hybridization (mFISH) in interphase cells. The results show that cyclin D1 is unaffected in all investigated cells. The p16INK4a gene locus was shown to be mutated in COLO cells but not in HMC. After labeling of CDK2 and RB1, hemizygous loss of one allele of each gene was observed in asbestos-treated HMC whereas gene amplification of these genes was detectable in MeT-5A and COLO cells. Our data indicate that disarrangement of the RB1 dependent pathway seems to be involved in mesothelioma formation.}, } @article {pmid12642917, year = {2002}, author = {Shimizudani, N and Morisako, T and Miyao, Y and Ito, M and Hatao, E and Kiyoi, K and Sudo, A and Kobayashi, K and Tsuchida, F and Adachi, H and Kishi, K and Yagyu, H and Oishi, S and Nakamura, H and Matsuoka, T}, title = {[A case of diffuse malignant mesothelioma of the pleura with bilateral chylothorax].}, journal = {Nihon Kokyuki Gakkai zasshi = the journal of the Japanese Respiratory Society}, volume = {40}, number = {10}, pages = {832-836}, pmid = {12642917}, issn = {1343-3490}, mesh = {Adult ; Chylothorax/*etiology ; Female ; Humans ; Mesothelioma/*complications ; Pleural Neoplasms/*complications ; }, abstract = {We describe a case of bilateral chylothorax with malignant pleural mesothelioma. A 41-year-old woman was admitted to our hospital because of dyspnea. She had no history of exposure to asbestos. A chest radiograph and chest computed tomogram (CT) on admission revealed massive bilateral pleural effusion and a large tumor with pleural thickening in the left lateral and anterior parts of the pleura and mediastinum. Biochemical tests of pleural fluid revealed chyle. Two years before, she had been diagnosed through histological and histochemical examinations as having diffuse malignant pleural mesothelioma of the epithelial type. Chest-tube drainage was performed, and pleurodesis was induced by the intrathoracic injection of OK-432 at 10 KE per dose. The chylothorax disappeared after pleurodesis. To date, reports of malignant mesothelioma with nontraumatic chylothorax have been rare.}, } @article {pmid12630438, year = {2003}, author = {Koskinen, K and Pukkala, E and Reijula, K and Karjalainen, A}, title = {Incidence of cancer among the participants of the Finnish Asbestos Screening Campaign.}, journal = {Scandinavian journal of work, environment & health}, volume = {29}, number = {1}, pages = {64-70}, doi = {10.5271/sjweh.706}, pmid = {12630438}, issn = {0355-3140}, mesh = {Asbestos/*adverse effects ; Female ; Finland/epidemiology ; Humans ; Incidence ; Male ; Mass Screening ; Middle Aged ; Neoplasms/chemically induced/classification/*epidemiology ; Occupational Diseases/diagnosis/*epidemiology ; Risk Assessment ; Surveys and Questionnaires ; }, abstract = {OBJECTIVES: Cancer risk has been estimated for asbestos production workers or other heavily exposed asbestos workers in numerous studies. The bulk of the asbestos epidemic results come, however, from past intermittent exposures during asbestos product use. This study concentrated on estimating the risk of cancer in such a population.

METHODS: Altogether 23285 men and 930 women invited to a nationwide screening campaign for benign asbestos-related diseases in 1990-1992 were followed for cancer through the Finnish Cancer Register up to 1998. Standardized incidence ratios (SIR) were calculated in comparison with the total Finnish population.

RESULTS: Altogether 1392 cases of cancer were found among the men. The risk was slightly, but significantly elevated for lung cancer [SIR 1.14, 95% confidence interval (95% CI) 1.01-1.26), mesothelioma (SIR 2.77, 95% CI 1.66-4.31), and prostate cancer (SIR 1.21, 95% CI 1.09-1.34). The risk of lung cancer was slightly higher among the invited nonparticipants (SIR 1.48, 95% CI 1.20-1.79) than among the participants (SIR 1.02, 95% CI 0.88-1.17). About 98% of the lung cancers occurred in current or ex-smokers.

CONCLUSIONS: In a population of long-term construction workers, the risk of lung cancer and mesothelioma was increased, but considerably lower than among insulators, asbestos sprayers, or patients with asbestosis. As it was not possible to follow most of the invited nonparticipants in the original screening study, selection bias by smoking or other life-style factors possibly correlated to the individual's decision to participate in the health screening cannot be excluded.}, } @article {pmid12616610, year = {2003}, author = {Kravchenko, IV and Furalyov, VA and Pylev, LN}, title = {Factors secreted by peritoneal macrophages are cytotoxic for transformed rat pleural mesothelium and mesothelioma cells.}, journal = {Teratogenesis, carcinogenesis, and mutagenesis}, volume = {Suppl 1}, number = {}, pages = {207-214}, doi = {10.1002/tcm.10076}, pmid = {12616610}, issn = {0270-3211}, mesh = {Animals ; Asbestos/toxicity ; Cell Line, Transformed ; Cell Transformation, Neoplastic/*drug effects/pathology ; Cytotoxins/*metabolism/*toxicity ; Epithelial Cells/cytology/*drug effects ; Macrophages, Peritoneal/*metabolism ; Mesothelioma/metabolism/pathology ; Neoplasms, Experimental/metabolism/pathology ; Peritoneal Neoplasms/metabolism/pathology ; Pleural Cavity/cytology/*drug effects ; Rats ; Rats, Wistar ; Tumor Cells, Cultured ; }, abstract = {The report is devoted to the investigation of cytotoxic action of macrophages and asbestos on transformed mesothelium and mesothelioma cells, the characterization of its specificity, and the nature of the factors mediating it. The viability of different cells after asbestos exposure was studied in co-culture with macrophages. Mesothelioma cell lines obtained from tumors developed in vivo were the most sensitive to the cytotoxic action of macrophages and asbestos. Mesothelium cells of late passages and ras-transformed cell lines IAR2 and Rat1 were somewhat less sensitive, whereas untransformed cells of IAR2 and Rat1 lines and early passage mesothelium were low sensitive to that cytotoxic action. In experiments performed on Petri dishes with inserts that allowed treatment with asbestos of only one of two cell populations, it was shown that asbestos treatment of mesothelioma cells was necessary and sufficient for manifestation of cytotoxic effect (in the absence of macrophages asbestos caused very low cytotoxicity). The medium conditioned by macrophages was not cytototoxic by itself but it strongly enhanced cytotoxic action of asbestos on transformed mesothelium and mesothelioma cells but not on normal mesothelial cells and IAR2 and Rat1 cells (both normal and ras-transformed). The specificity of this augmenting effect for different toxicants was also investigated. It was shown that medium conditioned by macrophages enhanced cytotoxicity of hydrogen peroxide and sodium azide but not that of nonfibrous silicon dioxide, ethylmethanesulfonate, and sodium dodecylsulfate. The factor mediating this effect is thermolabile, non-dialyzable and protease-sensitive. Its m.w. is approximately 3-5 kD.}, } @article {pmid12611196, year = {2002}, author = {Furet, Y and Bechtel, Y and Le Guellec, C and Bechtel, PR and Autret-Leca, E and Paintaud, G}, title = {[Clinical relevance of N-acetyltransferase type 2 (NAT2) genetic polymorphism].}, journal = {Therapie}, volume = {57}, number = {5}, pages = {427-431}, pmid = {12611196}, issn = {0040-5957}, mesh = {Acetylation ; Arylamine N-Acetyltransferase/*genetics ; Drug Hypersensitivity ; Genotype ; Humans ; Kinetics ; Pharmaceutical Preparations/metabolism ; Phenotype ; Polymorphism, Genetic/*genetics ; }, abstract = {Polymorphic N-acetyltransferase (NAT2) is involved in the metabolism of several compounds relevant in pharmacology or toxicology, with diverse clinical consequences. Inter-ethnic variations in distribution of the acetylation phenotype are significant. The caffeine test is most often used to assess the acetylation phenotype and to identify rapid and slow acetylators. The NAT2 phenotype could account for the increased risk of certain side effects in slow acetylators treated with isoniazid (particularly peripheral neuropathies and lupus erythematosus), although therapeutic efficacy seems to be independent of the acetylation status. Hypersensibility reactions with sulfonamides (including Lyell and Stevens-Johnson syndromes) are more frequent in slow acetylators, who also show poor tolerance to sulfasalazine and dapsone. In contrast, myelotoxicity induced by amonafide is more frequent in rapid acetylators, probably because of increased production of a toxic metabolite of the drug. In carcinogenesis, NAT2 may play a protective role against bladder cancer, although studies have shown contradictory results. Slow acetylators may have a risk of developing primitive liver cancer. For lung cancer, data are not conclusive, but slow acetylation status may predispose to mesothelioma in subjects exposed to asbestos. No relation has been found between acetylation phenotype and breast cancer. Contradictory results were reported on its role in colorectal cancer. Non-smoking type 1 diabetics may be at increased risk of nephropathy if they are rapid acetylators. Parkinson's disease may be more frequent among slow acetylators, but again, data have shown contradictory results. Finally, a poor acetylator phenotype may predispose to atopic diseases.}, } @article {pmid12607890, year = {2002}, author = {Eade, TN and Fulham, MJ and Constable, CJ}, title = {Primary malignant peritoneal mesothelioma: appearance on F-18 FDG positron emission tomographic images.}, journal = {Clinical nuclear medicine}, volume = {27}, number = {12}, pages = {924-925}, doi = {10.1097/00003072-200212000-00029}, pmid = {12607890}, issn = {0363-9762}, mesh = {Aged ; Asbestos/adverse effects ; *Fluorodeoxyglucose F18 ; Humans ; Male ; Mesothelioma/*diagnostic imaging/etiology/pathology ; Peritoneal Neoplasms/*diagnostic imaging/etiology/pathology ; Radiography ; Radiopharmaceuticals ; Tomography, Emission-Computed ; }, } @article {pmid12596421, year = {2002}, author = {Gorini, G and Silvestri, S and Merler, E and Chellini, E and Cacciarini, V and Seniori Costantini, AS}, title = {[Tuscany mesothelioma registry (1988-2000): evaluation of asbestos exposure].}, journal = {La Medicina del lavoro}, volume = {93}, number = {6}, pages = {507-518}, pmid = {12596421}, issn = {0025-7818}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Carcinogens/*adverse effects ; Female ; Humans ; Incidence ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*epidemiology/etiology ; *Registries ; }, abstract = {BACKGROUND: The Tuscany Mesothelioma Register (ARTMM) records pleural malignant mesothelioma cases of Tuscany residents, diagnosed by histological, cytological, or clinical (radiography or computerized tomography) examinations. The ARTMM began in 1988 and estimates mesothelioma incidence in Tuscany and collects information on past asbestos exposure of mesothelioma cases.

OBJECTIVES: The aim of this paper was to describe the incidence of pleural mesothelioma cases in Tuscany and to analyse their possible past asbestos exposures.

METHODS: We considered pleural mesothelioma cases recorded in ARTMM in the period 1988-2000 and interviews collected for these cases. In order to identify past asbestos exposure in the occupational and non-occupational history of patients, interviews were carried out using a standardised questionnaire.

RESULTS: In the period 1988-2000, 494 pleural malignant mesothelioma cases were recorded in the ARTMM; 82% were males. In the periods 1988-1993, 1994-1997, 1998-2000 the incidence rates, standardised on the Italian population (per 100,000), were respectively 1.15, 1.57, 2.58 among males; 0.29; 0.27; 0.29 among females. Information on occupational history was collected for 418 mesothelioma patients (85% of recorded cases): 173 mesothelioma cases were directly interviewed; for 245 cases relatives or work colleagues were interviewed. Occupational asbestos exposure was ranked as certain, probable or possible in 72% of the interviewed cases (80% of males; 20% of females). Environmental and non-occupational asbestos exposure was identified in 1% of males, and 3% of females. In 24% of the interviewed cases (15% of males; 74% of females) no known asbestos exposure was identified. Occupational asbestos exposure occurred in maritime activities (shipyards, dock work, merchant and regular Navy), the building industry, railway carriage construction and maintenance, rail transport, textile industries (mainly rag sorting), electricity production, asbestos cement manufacture, chemical, iron and steel industries and in glass manufacturing. In Tuscany two areas are distinguished for their well-documented and massive use of asbestos: the coastal areas (Livorno and Massa Carrara) for maritime activities, and the areas of Pistoia and Arezzo for railway carriage construction and repair. Mesothelioma incidence rates in these areas are the highest in the whole region.

CONCLUSIONS: Further investigation is needed in order to identify unknown asbestos uses and consequent exposure, in particular for females. Uncertainty as regards occurrence of asbestos exposure persists in the textile industries where the mesothelioma epidemics have not yet declined. Research hypotheses are addressed on the re-use of jute bags previously containing asbestos, therefore collection of further information on periods and methods of this recycling activity is essential.}, } @article {pmid12596420, year = {2002}, author = {Cristaudo, A and Foddis, R and Bigdeli, L and Vivaldi, A and Buselli, R and Guglielmi, G and Guidi, M and Ottenga, F}, title = {[SV40: a possible co-carcinogen of asbestos in the pathogenesis of mesothelioma?].}, journal = {La Medicina del lavoro}, volume = {93}, number = {6}, pages = {499-506}, pmid = {12596420}, issn = {0025-7818}, mesh = {Animals ; Asbestos/*adverse effects ; Carcinogens/*adverse effects ; Humans ; Mesothelioma/*etiology ; Pleural Neoplasms/*etiology ; Polyomavirus Infections/*complications ; *Simian virus 40 ; Tumor Virus Infections/*complications ; }, abstract = {BACKGROUND: The etiopathogenic role of asbestos in causing malignant mesothelioma of the pleura is clearly supported by an impressive amount of data. Despite the frequent association with previous exposure to asbestos, only a relatively small fraction of those exposed develop malignant mesothelioma. The long latency period between initial exposure and onset of the tumor suggests that human mesothelioma, like many other tumors, has a multi-stage evolution with the occurrence of many mutating events involving various tumorigenic agents, probably in part initiating and in part promoting development. Recently this has raised great interest in the scientific world, in an attempt to identify possible factors which together with asbestos may have a role in developing this rare malignant tumor. Ionizing radiations and genetic susceptibility have occasionally been identified as the culprits. A virus called SV40 has been gaining increasing scientific credibility since the mid 1990's as a potential co-carcinogen of asbestos.

OBJECTIVES: The aim of this article was to examine the supposed interaction between asbestos and SV40 in the pathogenesis of mesothelioma and the way this simian virus has become a human virus.

METHODS: All biomolecular and epidemiological data available from medical literature along with the results of the experiments performed during the last 7 years in our department laboratories were reviewed and compared.

RESULTS: The first two pieces of experimental evidence of the presence of SV40-like DNA sequences in mesothelioma samples were obtained in 1994 in the United States, and one year later in our laboratories. After these two studies many research groups started carrying out similar experiments, obtaining comparable results in most cases. Moreover, beyond the mere detection of viral DNA sequences large amount of biomolecular data has recently been added in favour of its role in the pathogenesis of mesothelioma. Epidemiological studies published to date were unable to provide similar unanimous results. Data regarding the source of human infection are still debatable, even if the inadvertent administration of contaminated poliovaccines to millions of people in Europe and the United States between 1955 and 1963 remains one of the most reasonable hypotheses.

CONCLUSIONS: On the basis of all the biomolecular data reviewed and partially on the basis of epidemiological studies, SV40 seems to be the best candidate as a cofactor with asbestos in the development of human mesothelioma.}, } @article {pmid12585037, year = {2003}, author = {Haba, T and Wakasa, K and Sasaki, M}, title = {Well-differentiated papillary mesothelioma in the pelvic cavity. A case report.}, journal = {Acta cytologica}, volume = {47}, number = {1}, pages = {88-92}, doi = {10.1159/000326481}, pmid = {12585037}, issn = {0001-5547}, mesh = {Calbindin 2 ; *Cytodiagnosis ; Endometriosis/surgery ; Female ; Humans ; Keratins/metabolism ; Mesothelioma/diagnosis/metabolism/*pathology ; Middle Aged ; Ovarian Cysts/pathology ; Ovarian Neoplasms/pathology ; Pelvic Neoplasms/diagnosis/*pathology ; Peritoneal Neoplasms/diagnosis/metabolism/*pathology ; S100 Calcium Binding Protein G/metabolism ; Thrombomodulin/metabolism ; }, abstract = {BACKGROUND: Well-differentiated papillary mesothelioma (WDPM) is considered to be a distinct subtype of peritoneal mesothelioma. It occurs in the peritoneum, is most commonly seen in young women and is found incidentally at laparotomy for other indications. Clinically, WDPM is considered to be benign or to have low malignancy potential.

CASE: A 48-year-old female with no history of asbestos exposure presented with hypermenorrhea. An operation was performed for adenomyosis, and six papillary nodules, 2 cm or less, were found in the serosa of the pelvic cavity. Peritoneal lavage fluid and imprint material from the tumor were obtained for cytologic examination. The cytologic specimens showed many scattered cells and sheetlike clusters and some papillary clusters. These cells had abundant, polygonal, cyanophilic cytoplasm; clearly outlined borders; and slitlike intercellular spaces. The cell arrangement was orderly. The nuclei were uniform in size, with a single centrally located nucleolus, and there were no binucleated forms or mitosis. There was no increase in chromatin. On the luminal surface of the cells, a brush border was observed.

CONCLUSION: It is important to differentiate WDPM from diffuse malignant mesothelioma or other peritoneal malignant tumors to avoid treating them as malignant tumors.}, } @article {pmid12572103, year = {2002}, author = {Bol, P}, title = {[Asbestos and mesothelioma].}, journal = {Nederlands tijdschrift voor tandheelkunde}, volume = {109}, number = {12}, pages = {497-498}, pmid = {12572103}, issn = {0028-2200}, mesh = {Asbestos/*adverse effects ; Humans ; Lung Neoplasms/epidemiology/*etiology/pathology/prevention & control ; Mesothelioma/epidemiology/*etiology/pathology/prevention & control ; Pleural Neoplasms/epidemiology/*etiology/pathology/prevention & control ; }, } @article {pmid12571809, year = {2002}, author = {Vogelzang, NJ}, title = {Emerging insights into the biology and therapy of malignant mesothelioma.}, journal = {Seminars in oncology}, volume = {29}, number = {6 Suppl 18}, pages = {35-42}, doi = {10.1053/sonc.2002.37469}, pmid = {12571809}, issn = {0093-7754}, mesh = {Antimetabolites, Antineoplastic/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Cisplatin/administration & dosage ; Clinical Trials as Topic ; Deoxycytidine/administration & dosage/*analogs & derivatives/therapeutic use ; Folic Acid Antagonists/*therapeutic use ; Glutamates/administration & dosage/*therapeutic use ; Guanine/administration & dosage/*analogs & derivatives/*therapeutic use ; Humans ; Mesothelioma/*drug therapy/epidemiology/etiology/pathology ; Pemetrexed ; Quinazolines/administration & dosage ; Thiophenes/administration & dosage ; Thymidylate Synthase/*antagonists & inhibitors ; Gemcitabine ; }, abstract = {Malignant mesothelioma is an aggressive malignancy that may be caused by environmental carcinogens (asbestos and erionite), viruses (SV40), and genetic predisposition. Pleural malignant mesotheliomas are far more common than the peritoneal variants. Diagnosis relies on radiographic studies as well as histology and molecular biologic analyses. The prognostic scoring systems of the Cancer and Leukemia Group B and the European Organization for Research and Treatment of Cancer are the most useful of those currently available. These systems rate performance status, age, histology, and hematologic parameters as the best prognostic factors for mesothelioma. Most patients with mesothelioma are not candidates for surgical or radiotherapy treatment, and cytotoxic agents are the only options. Historically, no classes or combinations of agents consistently yielded response rates over 20%. Recently, pemetrexed has been evaluated in phase I, II, and III clinical trials with promising results. The phase II trial showed an overall response rate of 14.1% with a 1-year survival rate of 47.8%. A phase III trial of cisplatin versus cisplatin and pemetrexed closed in February 2002 and a final analysis was presented in May 2002. Novel targeted agents are also being tested in clinical trials among mesothelioma patients and include drugs inhibiting the vascular endothelial growth factor and its receptor, the epidermal growth factor receptor, and platelet-derived growth factor receptor.}, } @article {pmid12562635, year = {2002}, author = {Suzuki, Y and Yuen, SR}, title = {Asbestos fibers contributing to the induction of human malignant mesothelioma.}, journal = {Annals of the New York Academy of Sciences}, volume = {982}, number = {}, pages = {160-176}, doi = {10.1111/j.1749-6632.2002.tb04931.x}, pmid = {12562635}, issn = {0077-8923}, mesh = {Asbestos/*adverse effects ; Body Burden ; Female ; Humans ; Lung/drug effects/pathology ; Lung Neoplasms/*chemically induced/epidemiology ; Male ; Mesothelioma/*chemically induced/epidemiology ; Occupational Diseases/*epidemiology ; Occupational Exposure ; Peritoneal Neoplasms/chemically induced/epidemiology ; Pleural Neoplasms/chemically induced/epidemiology ; }, abstract = {UNLABELLED: To elucidate the features of the asbestos fibers contributing to the induction of human malignant mesothelioma, we used high-resolution analytical electron microscopy to determine the type, number, and dimensions of asbestos fibers in lung and mesothelial tissues in 168 cases of mesothelioma.

RESULTS: 1. Asbestos fibers were present in almost all of the lung and mesothelial tissues from the mesothelioma cases. 2. The most common types of asbestos fibers in lung were either an admixture of chrysotile with amphiboles, amphibole alone, and occasionally chrysotile alone. In mesothelial tissues, most asbestos fibers were chrysotile. 3. In lung, amosite fibers were greatest in number followed by chrysotile, crocidolite, tremolite/actinolite, and anthophyllite. In mesothelial tissues, chrysotile fibers were 30.3 times more common than amphiboles. 4. In some mesothelioma cases, the only asbestos fibers detected in either lung or mesothelial tissue were chrysotile fibers. 5. The average number of asbestos fibers in both lung and mesothelial tissues was two orders of magnitude greater than the number found in the general population. 6. The majority of asbestos fibers in lung and mesothelial tissues were shorter than 5 micro m in length.

CONCLUSIONS: 1) Fiber analysis of both lung and mesothelial tissues must be done to determine the types of asbestos fibers associated with the induction of human malignant mesothelioma; 2) short, thin asbestos fibers should be included in the list of fiber types contributing to the induction of human malignant mesothelioma; 3) RESULTS support the induction of human malignant mesothelioma by chrysotile.}, } @article {pmid12541274, year = {2003}, author = {Dodson, RF and O'Sullivan, M and Brooks, DR and Hammar, SP}, title = {Quantitative analysis of asbestos burden in women with mesothelioma.}, journal = {American journal of industrial medicine}, volume = {43}, number = {2}, pages = {188-195}, doi = {10.1002/ajim.10164}, pmid = {12541274}, issn = {0271-3586}, mesh = {Aged ; Aged, 80 and over ; Asbestos, Amosite/adverse effects/*analysis ; Asbestos, Amphibole/adverse effects/*analysis ; Asbestos, Crocidolite/adverse effects/*analysis ; Asbestosis/etiology/pathology ; Body Burden ; Environmental Exposure/adverse effects ; Female ; Humans ; Lung/pathology ; Lung Neoplasms/etiology/*pathology ; Mesothelioma/etiology/*pathology ; Microscopy, Electron ; Middle Aged ; Mineral Fibers/adverse effects/analysis ; Occupational Exposure/adverse effects ; Reproducibility of Results ; }, abstract = {BACKGROUND: Lung tissue from 15 women who died from mesothelioma was evaluated for tissue burden of ferruginous bodies and uncoated asbestos fibers. The group contained individuals who had occupational exposure to asbestos and others had family members whose work history included vocations where contact with asbestos containing materials occurred.

METHODS: Tissue samples from tumor free lung were digested and filtered and then investigated for ferruginous bodies by light microscopy and asbestos and non-asbestos fibers by analytical transmission electron microscopy (ATEM). Size and type of fibers were also analyzed.

RESULTS: Asbestos bodies were found in 13 of the 15 samples and asbestos fibers were found in all cases. The most commonly found uncoated asbestos fiber in these individuals was amosite whereas tremolite was the second most commonly found form. The asbestos fiber burden in these females was often of mixed types.

CONCLUSIONS: The asbestos body and fiber burden in these cases show variation in tissue burden. Some cases in this study had appreciable burden, which was attributed to secondhand exposure from occupationally exposed family members. Mesothelioma can occur also in individuals with comparatively low tissue burdens of asbestos.}, } @article {pmid12539801, year = {2002}, author = {Ulvestad, B and Kjaerheim, K and Martinsen, JI and Damberg, G and Wannag, A and Mowe, G and Andersen, A}, title = {Cancer incidence among workers in the asbestos-cement producing industry in Norway.}, journal = {Scandinavian journal of work, environment & health}, volume = {28}, number = {6}, pages = {411-417}, doi = {10.5271/sjweh.693}, pmid = {12539801}, issn = {0355-3140}, mesh = {Aged ; Asbestos/*adverse effects/classification ; Asbestos, Amphibole/adverse effects ; Asbestos, Crocidolite/adverse effects ; Asbestos, Serpentine/adverse effects ; Cohort Studies ; Follow-Up Studies ; Humans ; Incidence ; Industry ; Lung Neoplasms/epidemiology/etiology ; Male ; Mesothelioma/epidemiology/etiology ; Middle Aged ; Neoplasms/classification/*epidemiology/etiology ; Norway/epidemiology ; Occupational Exposure/*adverse effects ; Poisson Distribution ; Registries ; Risk Factors ; Time ; }, abstract = {OBJECTIVES: The incidence of cancer among employees of a Norwegian asbestos-cement factory was studied in relation to duration of exposure and time since first exposure. The factory was active in 1942-1968. Most of the asbestos in use was chrysotile, but for technical reasons 8% amphiboles was added.

METHODS: For the identification of cancer cases, a cohort of 541 male workers was linked to the Cancer Registry of Norway. The analysis was based on the comparison between the observed and expected number of cancer cases. Standardized incidence ratios (SIR) and 95% confidence intervals (95% CI) were estimated. Period of first employment, duration of employment, and time since first employment were used as indicators of exposure. Poisson regression analysis was used for the internal comparisons.

RESULTS: The standardized incidence ratio was 52.5 (95% CI 31.1-83.0) for pleural mesothelioma, on the basis of 18 cases. The highest standardized incidence ratio was found for workers first employed in the earliest production period (SIR 99.0, 95% CI 51.3-173). No peritoneal mesothelioma was found. The standardized incidence ratio for lung cancer was 3.1 (95% CI 2.14.3), but no dose-response effect was observed. The ratio of mesothelioma to lung cancer cases was 1:2.

CONCLUSIONS: This study showed a high incidence of mesothelioma and a high ratio of mesothelioma to lung cancer among asbestos-cement workers. The high incidence of mesothelioma was probably due to the fact that a relatively high proportion of amphiboles was used in the production process.}, } @article {pmid12537760, year = {2002}, author = {Shia, J and Erlandson, RA and Klimstra, DS}, title = {Deciduoid mesothelioma: a report of 5 cases and literature review.}, journal = {Ultrastructural pathology}, volume = {26}, number = {6}, pages = {355-363}, doi = {10.1080/0913120290104647}, pmid = {12537760}, issn = {0191-3123}, mesh = {Abdominal Neoplasms/*ultrastructure ; Aged ; Deciduoma/*ultrastructure ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Male ; Mesothelioma/*ultrastructure ; Middle Aged ; Pleural Neoplasms/*ultrastructure ; }, abstract = {Deciduoid mesothelioma was first described in young females and in the peritoneum, which led to the suggestion that deciduoid mesothelioma was a distinct subtype with specific clinical and pathologic features. Later reports, however, have shown that this type of mesothelioma may also occur in elderly people and in the pleura. Cases reported in the literature so far are limited, and the disease is not well defined. The authors report the histologic, immunohistochemical, ultrastructural, and clinical findings of 5 cases of deciduoid mesothelioma, and review the literature reports. The results demonstrate that the presence of numerous cytoplasmic intermediate filaments, either dispersed or bundled, appear to be the likely ultrastructural basis for the deciduoid histologic appearance. Twenty-one cases of deciduoid mesothelioma were identified in the literature. Analyses of these 21 cases and the authors' 5 cases showed an age range of 13-78 years (median 53 years) and a slight female predominance (female to male ratio of 1.4:1). Fourteen of 26 cases (54%) occurred in the peritoneum. Seven of 20 patients (35%) had a documented history of asbestos exposure. Fifteen of 20 patients died, with a mean survival time of 7.33 months (range 1-21 months). Five of 20 patients were alive at a follow-up time of 8 months to 5 years. These findings suggest that the so-called deciduoid mesothelioma has some clinical and pathologic features that are dissimilar to mesothelioma in general. Whether it truly represents a pathogenetically distinct variant or merely an expansion of the morphologic spectrum awaits further studies.}, } @article {pmid12531361, year = {2003}, author = {Grégoire, M and Ligeza-Poisson, C and Juge-Morineau, N and Spisek, R}, title = {Anti-cancer therapy using dendritic cells and apoptotic tumour cells: pre-clinical data in human mesothelioma and acute myeloid leukaemia.}, journal = {Vaccine}, volume = {21}, number = {7-8}, pages = {791-794}, doi = {10.1016/s0264-410x(02)00600-x}, pmid = {12531361}, issn = {0264-410X}, mesh = {Apoptosis/*immunology ; Dendritic Cells/*immunology ; Humans ; Leukemia, Myeloid, Acute/immunology/*therapy ; Mesothelioma/immunology/secondary/*therapy ; Necrosis ; Neoplasm Metastasis ; }, abstract = {We have recently reported in an experimental model, that treatments based on the injections of dendritic cells which had phagocytosed apoptotic bodies derived from tumour cells were particularly effective in the cure of tumour-bearing animals. We proposed that systems using processing and presentation of antigenic molecules from antigen-presenting cells primed with apoptotic bodies can offer new opportunities in anti-cancer treatment. We first established the technical conditions for purification, characterisation and production of tumour cells isolated from fresh pleural liquid or blood. Then we compared efficacy of different apoptotic inducers agents on the cancer cells in culture. The apoptotic tumour cells were purified, characterised and maintained in coculture with monocytes-derived immature dendritic cells. We subsequently investigated the effect of the maturation process on phagocytosis of apoptotic bodies. We have shown that whatever the nature of the apoptotic cells they are phagocytosed by the dendritic cells which were efficiently matured using the combination of TNFalpha+Poly I:C. Furthermore, we demonstrated that the generation of the mature dendritic cells pulsed with apoptotic tumour cells, successfully generated CD4(+) (Th1) and CD8(+) (CTL) cells. All the experimental procedures that we have used were developed with clinical use in mind, using Good Manufacturing Products. We are presently investigating the feasibility of such a "vaccine" for the treatment of asbestos mesothelioma or acute myeloid leukaemia.}, } @article {pmid12528280, year = {2002}, author = {Alilović, M and Peros-Golubicić, T and Bekić, A and Tekavec-Trkanjec, J and Ivicević, A}, title = {Epidemiology of malignant pleural mesotheliomas in Croatia in the period from 1989 to 1998.}, journal = {Collegium antropologicum}, volume = {26}, number = {2}, pages = {551-556}, pmid = {12528280}, issn = {0350-6134}, mesh = {Adult ; Aged ; Asbestos ; Croatia/epidemiology ; Female ; Humans ; Incidence ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Pleural Neoplasms/*epidemiology ; }, abstract = {Malignant pleural mesotheliomas are rare tumors. Their occurrence is often associated with the exposure to asbestos. Asbestos is widely used in various industries as well as for many types of products in everyday use. In Croatia in the period from 1989 to 1998, the rate of incidence was 0.4-1.1/100,000. The highest rate of incidence was in the Districts of Istria (2.9) and Split-Dalmatia (2.5). It is more frequent among males than among females with a ratio of 3.2:1. It rarely occurs before the age of 40 and most of the patients suffering from the disease are more than 65 years old. About 12% of mesotheliomas metastasize into regional lymph nodes and 17% of them into distant organs. The disease unavoidably leads to death and, according to the data obtained in Croatia in the period from 1989 to 1998 the mortality and incidence are very close.}, } @article {pmid12518475, year = {2002}, author = {Buesing-Fedorow, JE}, title = {Malignant mesothelioma.}, journal = {Canadian oncology nursing journal = Revue canadienne de nursing oncologique}, volume = {12}, number = {4}, pages = {237-239}, pmid = {12518475}, issn = {1181-912X}, mesh = {Asbestos/adverse effects ; Community Health Nursing ; Humans ; Male ; Mesothelioma/diagnosis/etiology/*therapy ; Middle Aged ; Neoplasm Staging ; Occupational Exposure/adverse effects ; Pleural Neoplasms/diagnosis/etiology/*therapy ; }, } @article {pmid12502242, year = {2002}, author = {Bianchi, C and Ramani, L and Bianchi, T}, title = {Concurrent malignant mesothelioma of the pleura and hepatocellular carcinoma in the same patient: a report of five cases.}, journal = {Industrial health}, volume = {40}, number = {4}, pages = {383-387}, doi = {10.2486/indhealth.40.383}, pmid = {12502242}, issn = {0019-8366}, mesh = {Aged ; Asbestos/adverse effects ; Carcinoma, Hepatocellular/*complications ; Female ; Humans ; Immune System/drug effects/physiopathology ; Liver Neoplasms/*complications ; Male ; Mesothelioma/*complications ; Middle Aged ; *Neoplasms, Multiple Primary ; Pleural Neoplasms/*complications ; }, abstract = {Five cases are reported in which malignant mesothelioma of the pleura and hepatocellular carcinoma co-existed in the same patient. The group included four men and one woman, aged between 58 and 86 years. The diagnosis was established at necropsy. In one case the association was clinically suspected. All mesotheliomas were asbestos-related. Liver cirrhosis co-existed in four cases, two of them positive for HCV markers. A lot of elements suggest that the above association is not a fortuitous coincidence. In particular, asbestos could favour liver cancerogenesis by inducing immune impairment.}, } @article {pmid12502232, year = {2002}, author = {Guidotti, TL}, title = {Apportionment in asbestos-related disease for purposes of compensation.}, journal = {Industrial health}, volume = {40}, number = {4}, pages = {295-311}, doi = {10.2486/indhealth.40.295}, pmid = {12502232}, issn = {0019-8366}, mesh = {Asbestos/*adverse effects ; Asbestosis/diagnosis/*economics ; Canada ; Humans ; Lung Neoplasms/chemically induced ; Mesothelioma/chemically induced/diagnosis/economics ; Occupational Exposure/*economics ; Pulmonary Disease, Chronic Obstructive/chemically induced/diagnosis/economics ; *Risk Assessment ; Risk Factors ; Smoking/adverse effects/economics ; Workers' Compensation/*organization & administration ; }, abstract = {Workers' compensation systems attempt to evaluate claims for occupational disease on an individual basis using the best guidelines available to them. This may be difficult when there is more than one risk factor associated with the outcome, such as asbestos and cigarette smoking, and the occupational exposures is not clearly responsible for the disease. Apportionment is an approach that involves an assessment of the relative contribution of work-related exposures to the risk of the disease or to the final impairment that arises for the disease. This article discusses the concept of apportionment and applies it to asbestos-associated disease. Lung cancer is not subject to a simple tradeoff between asbestos exposure and smoking because of the powerful biological interaction between the two exposures. Among nonsmokers, lung cancer is sufficiently rare that an association with asbestos can be assumed if exposure has occurred. Available data suggest that asbestos exposure almost invariably contributes to risk among smokers to the extent that a relationship to work can be presumed. Thus, comparisons of magnitude of risk between smokers and nonsmokers are irrelevant for this purpose. Indicators of sufficient exposure to cause lung cancer are useful for purposes of establishing eligibility and screening claims. These may include a chest film classified by the ILO system as 1/0 or greater (although 0/1 does not rule out an association) or a history of exposure roughly equal to or greater than 40 fibres/cm3 x y. (In Germany, 25 fibres/cm3 x y is used.) The mere presence of pleural plaques is not sufficient. Mesothelioma is almost always associated with asbestos exposure and the association should be considered presumed until proven otherwise in the individual case. These are situations in which only risk of a disease is apportioned because the impairment would be the same given the disease whatever the cause. Asbestosis, if the diagnosis is correct, is by definition an occupational disease unless there is some source of massive environmental exposure; it is always presumed to be work-related unless proven otherwise. Chronic obstructive airways disease (COAD) accompanies asbestosis but may also occur in the context of minimal parenchymal fibrosis and may contribute to accelerated loss of pulmonary function. In some patients, particularly those with smoking-induced emphysema, this may contribute significantly to functional impairment. An exposure history of 10 fibre x years is suggested as the minimum associated with a demonstrable effect on impairment, given available data. Equity issues associated with apportionment include the different criteria that must be applied to different disorders for apportionment to work, the management of future risk (eg. risk of lung cancer for those who have asbestosis), and the narrow range in which apportionment is really useful in asbestos-associated disorders. Apportionment, attractive as it may be as an approach to the adjudication of asbestos-related disease, is difficult to apply in practice. Even so, these models may serve as a general guide to the assessment of asbestos-related disease outcomes for purposes of compensation.}, } @article {pmid12500463, year = {2002}, author = {Koskinen, K and Pukkala, E and Martikainen, R and Reijula, K and Karjalainen, A}, title = {Different measures of asbestos exposure in estimating risk of lung cancer and mesothelioma among construction workers.}, journal = {Journal of occupational and environmental medicine}, volume = {44}, number = {12}, pages = {1190-1196}, doi = {10.1097/00043764-200212000-00015}, pmid = {12500463}, issn = {1076-2752}, mesh = {Asbestos/*adverse effects ; Finland/epidemiology ; Humans ; Lung Neoplasms/diagnostic imaging/*etiology ; Male ; Mesothelioma/diagnostic imaging/*etiology ; Middle Aged ; Occupational Diseases/etiology ; Occupational Exposure/*adverse effects ; Occupations ; Radiography ; Risk Factors ; Smoking/epidemiology ; Time Factors ; }, abstract = {To analyze occupation, expert-evaluated cumulative exposure, and radiographic abnormalities as indicators of asbestos-related cancer risk we followed 16,696 male construction workers for cancer in 1990-2000. We calculated standardized incidence ratios (SIR) in comparison to the Finnish population and relative risks (RR) in a multivariate analysis in comparison to the internal low-exposure category of each indicator. Overall, the risk was increased for mesothelioma (SIR 2.0, 95% CI = 1.0-3.3), but not for lung cancer (SIR 1.1, 95% CI = 0.9-1.2). Radiographic lung fibrosis indicated a 2-fold and a high value of the exposure index a 3-fold RR of lung cancer, while there was no risk among those with pleural plaques. The risk of lung cancer was the highest in insulators (RR 3.7, 95% CI = 1.4-9.9). Occupation, expert-evaluated cumulative exposure, and lung fibrosis are useful indicators of lung cancer risk among construction workers.}, } @article {pmid12499457, year = {2003}, author = {Segura, O and Burdorf, A and Looman, C}, title = {Update of predictions of mortality from pleural mesothelioma in the Netherlands.}, journal = {Occupational and environmental medicine}, volume = {60}, number = {1}, pages = {50-55}, pmid = {12499457}, issn = {1351-0711}, mesh = {Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Cohort Studies ; Female ; Forecasting ; Humans ; Male ; Mesothelioma/*mortality ; Middle Aged ; Models, Statistical ; Netherlands/epidemiology ; Pleural Neoplasms/*mortality ; Sensitivity and Specificity ; Sex Distribution ; }, abstract = {AIMS: To predict the expected number of pleural mesothelioma deaths in the Netherlands from 2000 to 2028 and to study the effect of main uncertainties in the modelling technique.

METHODS: Through an age-period-cohort modelling technique, age specific mortality rates and cohort relative risks by year of birth were calculated from the mortality of pleural mesothelioma in 1969-98. Numbers of death for both sexes were predicted for 2000 to 2028, taking into account the most likely demographic development. In a sensitivity analysis the relative deviation of the future death toll and peak death number were studied under different birth cohort risk assumptions.

RESULTS: The age-cohort model on mortality 1969-98 among men showed the highest age specific death rates in the oldest age group (79 per 100 000 person-years in the age group 80-84 years) and the highest relative risks for the birth cohorts of 1938-42 and 1943-47. Among men a small period effect was observed. The age-cohort model was considered the best model for predicting future mortality. The most plausible scenario predicts an increase in pleural mesothelioma mortality up to 490 cases per year in men, with a total death toll close to 12 400 cases during 2000-28. However, using different assumptions this death toll could rise to nearly 15 000 in men (20% increase). Mortality among women remains low, with a total death toll of about 800 cases. It is predicted that the total death toll in the period 2000-28 is 44% lower than previous predictions using mortality data from 1969 to 1993.

CONCLUSION: Adding five recent years of observed mortality in an age-cohort model resulted in a 44% lower prediction of the future death toll of pleural mesothelioma. A statistically significant period effect was observed, possibly influenced by initial asbestos safety guidelines in the 1970s and introduction of the ICD-10 codification.}, } @article {pmid12499455, year = {2003}, author = {Luo, S and Liu, X and Mu, S and Tsai, SP and Wen, CP}, title = {Asbestos related diseases from environmental exposure to crocidolite in Da-yao, China. I. Review of exposure and epidemiological data.}, journal = {Occupational and environmental medicine}, volume = {60}, number = {1}, pages = {35-41; discussion 41-2}, pmid = {12499455}, issn = {1351-0711}, mesh = {Asbestos, Crocidolite/*adverse effects ; China/epidemiology ; Cohort Studies ; Environmental Exposure/*adverse effects ; Humans ; Lung Diseases/*epidemiology/mortality ; Mesothelioma/*epidemiology/mortality ; Pleural Diseases/*epidemiology/mortality ; Residence Characteristics ; Retrospective Studies ; Risk Assessment ; Soil ; }, abstract = {BACKGROUND: Scattered patches of crocidolite, one form of asbestos, were found in the surface soil in the rural county of Da-yao in southwestern China. In 1983, researchers from the West China University of Medical Sciences (WCUMS) discovered that residents of two villages in Da-yao had hyperendemic pleural plaques and excessive numbers of pleural mesotheliomas.

AIMS: To review and summarise epidemiological studies, along with other relevant data, and to discuss the potential contribution to environmental risk assessment.

METHODS: This report is based on a review of several clinical/epidemiological studies conducted by WCUMS researchers since 1984, which included one cross sectional medical examination survey, one clinical/pathological analysis of 46 cases of mesothelioma, and three retrospective cohort mortality studies. Additional information acquired from reviewing original data first hand during a personal visit along with an interview of medical specialists from Da-yao County Hospital was also incorporated.

RESULTS: The prevalence of pleural plaque was 20% among peasants in Da-yao over 40 years of age in the cross sectional survey. The average number of mesothelioma cases was 6.6 per year in the 1984-95 period and 22 per year in the 1996-99 period, in a population of 68 000. For those mesothelioma cases that were histology confirmed, there were 3.8 cases/year in the first period and 9 cases/year in the second. Of the 2175 peasants in this survey, 16 had asbestosis. Lung cancer deaths were significantly increased in all three cohort studies. The annual mortality rate for mesothelioma was 85 per million, 178 per million, and 365 per million for the three cohort studies, respectively. The higher exposed peasants had a fivefold increased mesothelioma mortality compared to their lower exposed counterparts. There were no cases of mesothelioma in the comparison groups where no crocidolite was known to exist in the environment. In the third cohort study, almost one of five cancer deaths (22%) was from mesothelioma. The ratio of lung cancer to mesothelioma deaths was low for all three studies (1.3, 3.0, and 1.2, respectively).

CONCLUSIONS: The observation of numerous mesothelioma cases at Da-yao was a unique finding, due mainly to their lifetime exposure to crocidolite asbestos. The finding of cases dying at a younger age and the relatively high ratio of mesothelioma cases to lung cancer could also be another unique result of lifetime environmental exposure to crocidolite asbestos. Although the commercial use of crocidolite has been officially banned since 1984, the incidence of mesothelioma has continued to show a steady increase, particularly among peasants. Since the latency of mesothelioma is approximately 30-40 years, the ban had little effect in the 1990s. The increased awareness and changes in diagnosis over time may also contribute to the increase. Furthermore, exposure to asbestos stoves and walls continued. The government implemented reduction of these exposures. However, from a public health standpoint, the most important issue is the complete avoidance of further exposure to asbestos.}, } @article {pmid12482127, year = {2002}, author = {Oksüzoğlu, B and Yalçin, S and Erman, M and Dağdelen, S}, title = {Leptomeningeal infiltration of malignant mesothelioma.}, journal = {Medical oncology (Northwood, London, England)}, volume = {19}, number = {3}, pages = {167-169}, pmid = {12482127}, issn = {1357-0560}, mesh = {Adult ; Asbestos/adverse effects ; Environmental Exposure ; Female ; Humans ; Lymphatic Metastasis ; Magnetic Resonance Imaging ; Meningeal Neoplasms/diagnostic imaging/*secondary ; Mesothelioma/diagnostic imaging/etiology/*pathology ; Peritoneal Neoplasms/etiology/*pathology ; Pleural Neoplasms/etiology/*pathology ; Radiography ; }, abstract = {Mesothelioma is a disease mostly involving the pleura, peritoneum, and pericardium. Hematogenously disseminated metastases involving the liver, adrenal glands, kidneys, and contralateral lung have been documented in some patients, but central nervous system (CNS) involvement, especially as leptomeningeal infiltration, is very rare. A 44-yr-old mesothelioma patient admitted to hospital with convulsions and diffuse leptomeningeal infiltration was shown with magnetic resonance imaging. She had a positive history for environmental asbestos exposure. Pleural and axillary lymph node biopsies were consistent with mesothelioma. Diffuse leptomeningeal infiltration is the only constant radiological finding reported as a diagnostic criteria for CNS involvement and histopathological confirmation is usually possible only at autopsy, so clinical and radiological diagnosis is essential after exclusion of other possible causes.}, } @article {pmid12479509, year = {2001}, author = {Dodson, RF and O'Sullivan, MF and Brooks, DR and Bruce, JR}, title = {Asbestos content of omentum and mesentery in nonoccupationally exposed individuals.}, journal = {Toxicology and industrial health}, volume = {17}, number = {4}, pages = {138-143}, doi = {10.1191/0748233701th101oa}, pmid = {12479509}, issn = {0748-2337}, mesh = {Adolescent ; Adult ; Asbestos/analysis/*pharmacokinetics ; Autopsy ; Body Burden ; Carcinogens/analysis/*pharmacokinetics ; Child ; *Environmental Exposure ; Female ; *Foreign-Body Migration ; Humans ; Lung/*chemistry ; Male ; Mesentery/*chemistry ; Microscopy, Electron ; Middle Aged ; Mineral Fibers ; Omentum/*chemistry ; }, abstract = {Asbestos fibers in occupationally exposed individuals relocate from the lung to extrapulmonary sites. A mechanism for relocation is via the lymphatic circulation. Indeed, asbestos fibers have been found in lymph nodes as well as pleural plaques. Our laboratory has recently shown that asbestos fibers also reach the mesentery and omentum in the peritoneal area where a small percentage of mesotheliomas occurs in exposed individuals. The present study uses light and analytical transmission electron microscopy for defining the asbestos burden in digested lung, omentum, and mesentery tissues from individuals considered as representing the general population in East Texas. The findings, when compared with previous data from occupationally exposed individuals, indicate extreme contrasts as to the level and types of fiber burden between individuals representing the groups.}, } @article {pmid12475867, year = {2002}, author = {Metintas, S and Metintas, M and Ucgun, I and Oner, U}, title = {Malignant mesothelioma due to environmental exposure to asbestos: follow-up of a Turkish cohort living in a rural area.}, journal = {Chest}, volume = {122}, number = {6}, pages = {2224-2229}, doi = {10.1378/chest.122.6.2224}, pmid = {12475867}, issn = {0012-3692}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*poisoning ; Environmental Exposure/*adverse effects ; Female ; Humans ; Male ; Mesothelioma/chemically induced/*epidemiology/mortality ; Middle Aged ; Pleural Neoplasms/chemically induced/*epidemiology ; Rural Population ; Soil Pollutants/*adverse effects ; Turkey/epidemiology ; }, abstract = {STUDY OBJECTIVES: This study examines the incidence of malignant pleural mesothelioma (MPM) in a rural population of Turkey with environmental exposure to asbestos-contaminated soil mixtures (white soil).

DESIGN: A field-based epidemiologic study.

SETTING AND SUBJECTS: A cohort of villagers (the "Eskisehir" cohort) from 11 villages around Eskisehir in central Anatolia, who had been environmentally exposed to asbestos due to the use of white soil.

MEASUREMENTS: The mineral content and asbestos contamination of the white soil used in these villages was determined, as well as airborne fiber concentrations. Cohort members' details of age, sex, ambient exposure data, duration of residence in the villages, and hospital records, including pathologic diagnosis, were recorded.

RESULTS: The Eskisehir cohort consisted of 1,886 villagers. During the observation time, 377 deaths occurred and 24 MPM cases were diagnosed. Average annual mesothelioma incidence rates were 114.8/100,000 for men and 159.8/100,000 for women.

CONCLUSIONS: These data indicate that the risk of mesothelioma is 88.3 times greater in men and 799 times greater in women, respectively, in comparison to world background incidence rates.}, } @article {pmid12465702, year = {2002}, author = {Downs, FM and Giles, GM and Johnson, MJ}, title = {Palliative physicians persuade procurators fiscal.}, journal = {Palliative medicine}, volume = {16}, number = {6}, pages = {532-539}, doi = {10.1191/0269216302pm594oa}, pmid = {12465702}, issn = {0269-2163}, mesh = {Asbestos/*adverse effects ; Attitude of Health Personnel ; Cause of Death ; Coroners and Medical Examiners ; Humans ; Male ; Medical Records ; Mesothelioma/*etiology/psychology ; Middle Aged ; Occupational Diseases/*etiology/psychology ; Occupational Exposure/*adverse effects ; United Kingdom ; Workers' Compensation/*legislation & jurisprudence ; }, abstract = {Mesothelioma caused by occupational exposure to asbestos is well recognized and sufferers who have been employed in a prescribed occupation can claim compensation. Stringent criteria must be fulfilled in order to establish the link between occupational exposure and mesothelioma, and to this end the procurator fiscal is involved after the patient's death, both to elucidate the individual situation and 'for the common good'. Problems were experienced locally by the use of uniformed police officers, as the appointed Crown agents, as interviewers of recently bereaved relatives, irrespective of the degree of tact and sensitivity shown. The likelihood of an autopsy was also distressing. It is important to recognize the role of the procurator fiscal and to ensure that workers' compensation procedures exist and are followed. However, in order to minimize grief and distress to relatives, discussion took place with the local procurator fiscal. He was appreciative of the issues raised and practice has now changed substantially. In particular, police officers are no longer required to interview relatives either for the purpose of identification or to ascertain the deceased's occupational history. A pro forma has been produced and agreed locally to obviate the need for medical staff to be interviewed by police officers. Following subsequent discussion with the Crown Office our local arrangements have been incorporated in Crown Office guidance for national use.}, } @article {pmid12462454, year = {2002}, author = {Szeszenia-Dabrowska, N and Urszula, W and Szymczak, W and Strzelecka, A}, title = {Mortality study of workers compensated for asbestosis in Poland, 1970-1997.}, journal = {International journal of occupational medicine and environmental health}, volume = {15}, number = {3}, pages = {267-278}, pmid = {12462454}, issn = {1232-1087}, mesh = {Adult ; Aged ; Asbestosis/complications/*mortality ; Cause of Death ; Cohort Studies ; Female ; Humans ; Lung Neoplasms/complications/*mortality ; Male ; Mesothelioma/complications/*mortality ; Middle Aged ; Occupational Diseases/complications/*mortality ; Pleural Neoplasms/complications/*mortality ; Poland/epidemiology ; Risk Assessment ; Workers' Compensation ; }, abstract = {The aim of the study was to assess the risk of asbestos-related malignancies among persons with diagnosed asbestosis. The study covered a cohort composed of 907 men and 490 women afflicted by asbestosis, diagnosed is 1970-1997. The follow-up of the cohort continued until 31 December 1999. In all, 421 deaths were registered and causes of death were retrieved for 93.3% of the deceased. A significantly increased mortality was observed both in the male 1300 deaths; SMR = 127; 95%CI: 113-142) and female (121 deaths, SMR = 150; 95%CI: 124-179) cohorts. The elevated number of deaths in the male and female cohorts were noted mainly due to respiratory diseases (men: 42 deaths; SMR = 344; 95%CI: 248-465; women: 20 deaths, SMR = 789; 95%CI: 482-1219) malignant neoplasms (men: 91 deaths, SMR = 146; 95%CI: 118-179; women: 34 deaths, SMR = 159; 95%CI: 110-222), including lung cancer (men: 39 deaths, SMR = 168; 95% CI: 119-230; women: 13 deaths, SMR = 621; 95%CI: 331-1062) and pleural mesothelioma (men: 3 deaths, SMR = 2680; 95%CI: 553-7832; women: 3 deaths, SMR = 7207; 95%CI: 1031-14612). Taking into account a cumulative dose of fibers, it was found that a significantly increased mortality from lung cancer and pleural mesothelioma applied to persons exposed to a dose above 25 f-y/ml. The results indicate that persons with asbestosis are at higher risk of developing malignant neoplasms, especially lung cancer and mesothelioma.}, } @article {pmid12457103, year = {2002}, author = {de La Provôté, S and Desoubeaux, N and Paris, C and Letourneux, M and Raffaelli, C and Galateau-Salle, F and Gignoux, M and Launoy, G}, title = {Incidence of digestive cancers and occupational exposure to asbestos.}, journal = {European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP)}, volume = {11}, number = {6}, pages = {523-528}, doi = {10.1097/00008469-200212000-00003}, pmid = {12457103}, issn = {0959-8278}, mesh = {Adult ; Age Factors ; Asbestos/*adverse effects ; Digestive System Neoplasms/epidemiology/*etiology ; Female ; France/epidemiology ; Humans ; Incidence ; Male ; Occupational Exposure/*adverse effects ; Poisson Distribution ; Registries ; Retrospective Studies ; Time Factors ; }, abstract = {While the role of exposure to asbestos in the development of several cancers such as mesotheliomas and bronchopulmonary cancers is now well established, the possible relationship between digestive cancers, other than peritoneal mesotheliomas, and occupational exposure to asbestos is still controversial. The great majority of the studies are based on mortality data. The aim of the study was to analyse the relationship between digestive cancer incidence and occupational exposure to asbestos in a population of subjects for whom precise occupational exposure data and precise incidence data were available. The population consisted of salaried and retired workers from a company using asbestos to manufacture fireproof textiles and friction materials. There were 1454 men (79.9%) and 366 women (20.1%). A cumulative exposure index and a mean exposure concentration in fibres/ml for each subject were calculated with the aid of an in-house job-exposure matrix. The number of cases of digestive cancer observed was compared with the expected and Standardized Incidence Ratio (SIR) was estimated. Precise occupational exposure data allowed us to study the dose-response relationship between asbestos exposure and risk of digestive cancer using Cox model. Fifty-six digestive cancers occurred in the study population over the 18-year follow-up period for 48.4 expected (SIR = 1.16 [0.87-1.50]). Comparing with incidence in the county, SIR was not significant for any of the digestive localization, but for peritoneum. However, even after taking into account the potential confounders via the Cox model, there was a significant dose-response relationship between the occurrence of digestive cancers and the mean exposure concentration, even after exclusion of peritoneum cancers. Our study provides initial evidence suggesting a relationship between occupational exposure to asbestos and the risk of digestive cancer: first, it is a study of incidence although the risk evidenced is not significant; secondly, a dose-effect relationship is demonstrated in the whole population. However, these preliminary results require confirmation by more powerful studies focusing on larger series.}, } @article {pmid12455070, year = {2003}, author = {Hemminki, K and Li, X}, title = {Mesothelioma incidence seems to have leveled off in Sweden.}, journal = {International journal of cancer}, volume = {103}, number = {1}, pages = {145-146}, doi = {10.1002/ijc.10806}, pmid = {12455070}, issn = {0020-7136}, mesh = {Age Distribution ; Aged ; Asbestos/adverse effects ; Female ; Humans ; Incidence ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Diseases/*epidemiology/etiology ; Occupational Exposure/adverse effects ; Pleural Neoplasms/*epidemiology/etiology ; Registries ; Sweden/epidemiology ; }, } @article {pmid12432244, year = {2002}, author = {Powers, A and Carbone, M}, title = {The role of environmental carcinogens, viruses and genetic predisposition in the pathogenesis of mesothelioma.}, journal = {Cancer biology & therapy}, volume = {1}, number = {4}, pages = {348-353}, pmid = {12432244}, issn = {1538-4047}, support = {R0-1 CA 09265701/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Asbestos/adverse effects ; Environmental Exposure ; *Genetic Predisposition to Disease ; Humans ; Lung Neoplasms/*etiology/*genetics/*virology ; Mesothelioma/*etiology/*genetics ; Models, Biological ; Simian virus 40/pathogenicity ; }, abstract = {Mesothelioma is one of the most aggressive human cancers and kills approximately 2500 people per year in the US. This cancer was almost unknown until the second half of the 20th century, and its rapid increase has been linked to the widespread use of asbestos. In spite of an enormous research effort, the mechanisms of asbestos carcinogenicity have remained an enigma. Why only a fraction of individuals exposed to high levels of asbestos develop mesothelioma while individuals with low to no asbestos exposure also develop this cancer remains unknown. Recently, simian virus 40, a DNA tumor virus known to preferentially cause mesotheliomas in hamsters, and genetic factors have been linked to mesothelioma development. Therefore, a new research front has been opened in mesothelioma, a cancer that appears to be caused by the environmental carcinogens asbestos and erionite, viruses, and genetic predisposition. The challenge for future research is to establish how these apparently very different factors interact to cause mesotheliomas.}, } @article {pmid12428402, year = {2002}, author = {Nakagomi, T and Kitada, O and Nakamura, H and Miyata, S and Aragane, K and Kodama, T and Kuribayashi, K and Jin, S and Takenaka, N and Nagasawa, N and Sugita, M}, title = {[An autopsy case of desmoplastic malignant mesothelioma].}, journal = {Nihon Kokyuki Gakkai zasshi = the journal of the Japanese Respiratory Society}, volume = {40}, number = {8}, pages = {697-702}, pmid = {12428402}, issn = {1343-3490}, mesh = {Humans ; Liver Neoplasms/pathology/*secondary ; Male ; Mesothelioma/pathology/*secondary ; Middle Aged ; Pleural Effusion, Malignant/pathology ; Pleural Neoplasms/*pathology ; }, abstract = {On November 15, 2000, a 60-year-old man was admitted to our hospital with progressive dyspnea and right chest pain. He had a 40-year history of occupational asbestos exposure, which began when he was 20 years old. On admission, his chest radiographs showed pleural effusion on the right side, and asbestos bodies were detected in his sputum. Neither a cytological examination of the pleural effusion nor a histological examination of the pleura by percutaneous pleural biopsy revealed malignant cells. In addition, we could not find any other cause for the pleural effusion (such as tuberculosis, collagen disease, or heart failure). In May 2001, the patient also developed pleural thickening and pain in the right hypochondrium, and he was readmitted to our hospital on May 21, 2001. On readmission, an enhanced abdominal CT showed multiple liver tumors, and percutaneous pleural and liver biopsies were performed. The histological findings in the pleura and liver specimens revealed hypocellular collagen tissues without malignant cells. Thus, we could not determine the main cause either of the pleural effusion or of the patient's disease. However, his condition rapidly deteriorated, and he died on August 12, 2001. At the autopsy, bilateral pleural thickening, predominantly on the right side, and invasion of the lungs were observed. The histological findings in the pleural and hepatic tissues revealed hypocellular collagen fibers with a striate pattern and areas of neoplastic spindle cells. He was diagnosed as having malignant desmoplastic mesothelioma with liver metastasis. Cases of malignant desmoplastic mesothelioma have rarely been reported in Japan.}, } @article {pmid12420184, year = {2002}, author = {Winter, M and Pfeifer, A and Waldfahrer, F and Kraus, T and Raithel, HJ and Iro, H}, title = {[Findings in a high-risk group following asbestos exposure. Benefit of ENT examinations in patients with long-term exposure to asbestos].}, journal = {HNO}, volume = {50}, number = {11}, pages = {989-996}, doi = {10.1007/s00106-002-0687-8}, pmid = {12420184}, issn = {0017-6192}, mesh = {Aged ; Alcohol Drinking/adverse effects ; Asbestos/*adverse effects ; Asbestosis/diagnostic imaging/pathology ; *Dust ; Humans ; Laryngeal Neoplasms/*diagnostic imaging/pathology ; Lung Neoplasms/diagnostic imaging/pathology ; Mesothelioma/diagnostic imaging/pathology ; Middle Aged ; Neoplasm Staging ; Occupational Diseases/*diagnostic imaging/pathology ; Occupational Exposure/*adverse effects ; Otolaryngology ; Otorhinolaryngologic Neoplasms/*diagnostic imaging/pathology ; *Patient Care Team ; Pleural Neoplasms/diagnostic imaging/pathology ; Precancerous Conditions/*diagnostic imaging/pathology ; Risk Factors ; Smoking/adverse effects ; *Tomography, X-Ray Computed ; }, abstract = {BACKGROUND AND OBJECTIVE: Laryngeal diseases caused by exposure to asbestos are listed in the current German list of occupational diseases under number 4104. Parallel to a multicenter study to evaluate whether a CT scan should be included in the examinations for occupational diseases according to the German surveillance guidelines, an additional ENT examination was evaluated.

PATIENTS AND METHODS: One hundred workers with a mean exposure time to asbestos of 20.9 years were given a complete ENT examination in 4 consecutive years (1993-1996). Radiological signs for asbestosis were observed in 21 cases and 58 participants had pleural affections caused by asbestos. Significant nicotine abuse was reported by 15 persons: 61 participants were ex-smokers and 24 had never smoked. Regular alcohol consumption was reported by 90% (11% more than 80 g/day).

RESULTS: As documented in the literature, we found a high prevalence of laryngitis, especially in smoking patients. One patient had early laryngeal cancer (T1).

CONCLUSION: The integration of an ENT examination into the German surveillance guidelines for occupational diseases should be discussed for patients with a high exposure to asbestos.}, } @article {pmid12419589, year = {2002}, author = {Musti, M and Cavone, D and Aalto, Y and Scattone, A and Serio, G and Knuutila, S}, title = {A cluster of familial malignant mesothelioma with del(9p) as the sole chromosomal anomaly.}, journal = {Cancer genetics and cytogenetics}, volume = {138}, number = {1}, pages = {73-76}, doi = {10.1016/s0165-4608(02)00575-7}, pmid = {12419589}, issn = {0165-4608}, mesh = {Adult ; Asbestos/adverse effects ; *Chromosome Deletion ; Chromosomes, Human, Pair 9/*genetics ; Environmental Exposure ; Female ; Genetic Predisposition to Disease ; Humans ; Male ; Mesothelioma/*genetics/*pathology ; Pedigree ; Peritoneal Neoplasms/*genetics/pathology ; Pleural Neoplasms/*genetics/pathology ; }, abstract = {We describe a family of three sisters affected by malignant mesothelioma (MM) (2 pleural and 1 peritoneal) and one brother affected by pleural plaques. All members of the family had been subjected to previous asbestos exposure of environmental-residential type. For 13 years, from 1951 to 1964, their housing was provided by the father's employer, an asbestos cement factory, and the factory warehouse was on the ground floor of the building they lived in. DNA extracted from paraffin-embedded MM samples was used to search for chromosomal alterations by a comparative genomic hybridization (CGH) method. In two cases, a loss at 9p was found to be the only change. The loss at 9p is a frequent event in malignant mesothelioma and the fact that this anomaly was diagnosed in two sisters as the only alteration suggests that this region may be the site of one or more oncosuppressor genes that could play an important role in the development of MM and in inducing greater genetic susceptibility to the carcinogenic effects of asbestos.}, } @article {pmid12418711, year = {2001}, author = {Richter, ED and Chlamtac, N and Berman, T and Laster, R}, title = {A review of environmental and occupational exposure to asbestos in Israel.}, journal = {Public health reviews}, volume = {29}, number = {2-4}, pages = {247-264}, pmid = {12418711}, issn = {0301-0422}, mesh = {Asbestos/*adverse effects ; Asbestosis/etiology/prevention & control ; Compensation and Redress ; Construction Materials/*adverse effects ; *Environmental Exposure/*adverse effects/analysis/prevention & control ; Hazardous Substances/adverse effects ; Humans ; Industry ; Israel ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Occupational Exposure/adverse effects/analysis/prevention & control ; Residence Characteristics ; Risk Assessment ; *Social Control, Formal ; Urban Health ; Waste Management ; }, abstract = {The case for a total ban on manufacture and use of asbestos products is stated by the history of asbestos use, exposures, and risks in Israel. Manufacture and use of asbestos began in Israel in the 1950s, rising to a peak in the mid-1970s, and dropping gradually thereafter until reaching minimal levels in the 1990s. Following heightened public concern regarding the carcinogenic effects of asbestos products, there were reductions in use, manufacture, and persons exposed. Since the 1960s, asbestos-related diseases have been diagnosed in hundreds patients nationwide, including asbestos workers and users, as well as individuals living proximally to the manufacturing facilities. Exposures to asbestos in place remain, and patients with asbestos-related disease from environmental exposure are expected to appear for at least another 20-30 years. In the 1980s, an advisory committee appointed by the Ministry of Health of Israel outlined a comprehensive approach towards prevention, control, management, and compensation for health risks from asbestos exposures. As certain areas are still contaminated with asbestos waste and as environmental exposure persists, continued and improved medical monitoring and compensation programs are urgently needed in order to reduce the suffering of exposed individuals and their families. The ban on asbestos prevents risks from new exposures, but does not undo the damage from past manufacture, use, disposal, and dumping. In this paper, we review the history of Israel's import and use of asbestos, and the management of occupational and environmental exposures. We also address policy, practice, and the need to protect future victims of asbestos-related disease.}, } @article {pmid12418710, year = {2001}, author = {LaDou, J and Landrigan, P and Bailar, JC and Foa, V and Frank, A and , }, title = {A call for an international ban on asbestos.}, journal = {Public health reviews}, volume = {29}, number = {2-4}, pages = {241-246}, pmid = {12418710}, issn = {0301-0422}, mesh = {*Asbestos/poisoning ; Asbestosis/etiology/prevention & control ; Construction Materials/*adverse effects ; Environmental Health/legislation & jurisprudence ; Humans ; *International Cooperation ; Lung Neoplasms/etiology/prevention & control ; Mesothelioma/etiology/prevention & control ; Mining/*legislation & jurisprudence ; Occupational Health/legislation & jurisprudence ; *Social Control, Formal ; }, } @article {pmid12417972, year = {2002}, author = {Cavazza, A and Rossi, G and Agostini, L and Facciolongo, N and De Marco, L and Putrino, I and Gardini, G}, title = {[Small-cell mesothelioma of the pleura: description of a case].}, journal = {Pathologica}, volume = {94}, number = {5}, pages = {247-252}, doi = {10.1007/s102420200040}, pmid = {12417972}, issn = {0031-2983}, mesh = {Asbestos/adverse effects ; Biomarkers, Tumor/analysis ; Carcinoma, Small Cell/chemically induced/chemistry/diagnosis/*pathology ; Construction Materials ; Diagnosis, Differential ; Fatal Outcome ; Female ; Humans ; Mesothelioma/chemically induced/chemistry/diagnosis/*pathology ; Middle Aged ; Neoplasm Proteins/analysis ; Occupational Diseases/chemically induced/diagnosis/*pathology ; Pleural Neoplasms/chemically induced/chemistry/diagnosis/*pathology ; }, abstract = {A case of mesothelioma with a small cell component in a 53-year-old, non-smoker woman. The patient had a history of asbestos exposure, and presented with thoracic pain. A total body computed tomogram showed a left pleural effusion and a 7.5-cm pleural mass. Thoracoscopy revealed a diffuse nodular thickening of the left parietal pleura, and a biopsy was performed. The patient died of the disease 4 months after diagnosis. Microscopically, the pleural neoplasm was composed of three different components: 40% of the tumor showed the classic histology of a malignant epithelial mesothelioma, 40% was composed of small- to medium-sized cells with open nuclear chromatin, evident nucleoli and high mitotic activity, and 20% of the neoplasm was indistinguishable from a small cell carcinoma. Immunohistochemically, the first component was diffusely and strongly positive for cytokeratin AE1/AE3, cytokeratin CAM 5.2 and EMA, focally positive for BER-EP4, and negative for CD15, B 72.3, CEA, LCA, chromogranin, synaptophysin, TTF-1 and CD99. The cells of the second component were positive only for cytokeratin AE1/AE3 and cytokeratin CAM 5.2, and the elements of the third component were negative for all the antibodies tested. Pleural mesothelioma with a small cell component is rare. The most useful parameters to distinguish it from other small cell malignancies that may involve the pleura, particularly small cell carcinoma of pulmonary origin, are discussed.}, } @article {pmid12414630, year = {2002}, author = {Ramos-Nino, ME and Timblin, CR and Mossman, BT}, title = {Mesothelial cell transformation requires increased AP-1 binding activity and ERK-dependent Fra-1 expression.}, journal = {Cancer research}, volume = {62}, number = {21}, pages = {6065-6069}, pmid = {12414630}, issn = {0008-5472}, support = {ES/HL09213/ES/NIEHS NIH HHS/United States ; P01 HL67004/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Asbestos/toxicity ; Cell Division/physiology ; Cell Transformation, Neoplastic/genetics/*metabolism ; DNA, Neoplasm/metabolism ; Enzyme Activation ; Epithelium/drug effects/*metabolism ; MAP Kinase Signaling System/drug effects/physiology ; Mesothelioma/etiology/*metabolism/pathology ; Mitogen-Activated Protein Kinase 1/antagonists & inhibitors/*metabolism ; Mitogen-Activated Protein Kinase 3 ; Mitogen-Activated Protein Kinases/antagonists & inhibitors/*metabolism ; Mutation ; Phosphorylation ; Pleura/cytology/drug effects ; Proto-Oncogene Proteins c-fos/*biosynthesis/genetics ; Rats ; Rats, Inbred F344 ; Transcription Factor AP-1/*metabolism ; Tumor Cells, Cultured ; }, abstract = {Mesothelioma is a unique and insidious tumor associated historically with occupational exposure to asbestos. The transcription factor, activator protein-1 (AP-1) is a major target of asbestos-induced signaling pathways. Here, we demonstrate that asbestos-induced mesothelial cell transformation is linked to increases in AP-1 DNA binding complexes and the AP-1 component, Fra-1. AP-1 binding to DNA was increased dramatically in mesothelioma cell lines in comparison to isolated rat pleural mesothelial (RPM) cells. Elevated levels of AP-1 complexes, including significant increases in c-Jun, JunB and Fra-1, were found in asbestos-exposed RPM cells, but only Fra-1 expression was significantly increased and protracted in both asbestos-exposed RPM cells and mesothelioma cell lines. Asbestos-induced Fra-1 expression in RPM cells was dependent on stimulation of the extracellular signal-regulated kinases (ERKs 1/2). Inhibition of ERK phosphorylation or transfection with dominant-negative fra-1 constructs reversed the transformed phenotype of mesothelioma cells and anchorage-independent growth in soft agar. In summary, we demonstrate that ERK-dependent Fra-1 is elevated in AP-1 complexes in response to asbestos fibers and is critical to the transformation of mesothelial cells.}, } @article {pmid12394231, year = {2002}, author = {Değertekin, H and Yalçin, K and Işik, R}, title = {Peritoneal mesothelioma associated with exposure to asbestos in southeastern Turkey.}, journal = {Journal of clinical gastroenterology}, volume = {35}, number = {5}, pages = {409}, doi = {10.1097/00004836-200211000-00011}, pmid = {12394231}, issn = {0192-0790}, mesh = {Asbestos/*adverse effects ; Female ; Humans ; Male ; Mesothelioma/*etiology ; Middle Aged ; Peritoneal Neoplasms/*chemically induced/*etiology ; Turkey ; }, } @article {pmid12380138, year = {2002}, author = {Pickl, S}, title = {[New data from the American Cancer Congress. Asbestos-related tumors continue on the rise].}, journal = {MMW Fortschritte der Medizin}, volume = {144}, number = {33-34}, pages = {15}, pmid = {12380138}, issn = {1438-3276}, mesh = {Asbestosis/*mortality ; Carcinoma, Non-Small-Cell Lung/*mortality/therapy ; Cause of Death/*trends ; Humans ; Lung Neoplasms/*mortality/therapy ; Mesothelioma/*mortality/therapy ; Pleural Neoplasms/*mortality/therapy ; Survival Rate ; United States ; }, } @article {pmid12376609, year = {2002}, author = {Roach, HD and Davies, GJ and Attanoos, R and Crane, M and Adams, H and Phillips, S}, title = {Asbestos: when the dust settles an imaging review of asbestos-related disease.}, journal = {Radiographics : a review publication of the Radiological Society of North America, Inc}, volume = {22 Spec No}, number = {}, pages = {S167-84}, doi = {10.1148/radiographics.22.suppl_1.g02oc10s167}, pmid = {12376609}, issn = {0271-5333}, mesh = {Asbestos/*adverse effects ; Asbestosis/*diagnostic imaging/etiology/pathology ; *Carcinogens ; Carcinoma, Bronchogenic/diagnostic imaging/etiology/pathology ; Humans ; Lung Neoplasms/diagnostic imaging/etiology/pathology ; Mesothelioma/diagnostic imaging/etiology/pathology ; Mineral Fibers/adverse effects ; Pleura/diagnostic imaging/pathology ; Pleural Diseases/*diagnostic imaging/etiology/pathology ; Pleural Effusion/diagnostic imaging/etiology/pathology ; Pleural Neoplasms/diagnostic imaging/etiology/pathology ; Pulmonary Atelectasis/diagnostic imaging/etiology/pathology ; Radiography ; }, abstract = {Asbestos-related neoplastic and nonneoplastic diseases of the lungs and pleura range from pleural effusion and pleural plaques to lung cancer and malignant mesothelioma. Pleural effusions are typically hemorrhagic exudates of mixed cellularity but do not typically contain asbestos bodies. The classic distribution of pleural plaques seen on chest radiographs is the posterolateral chest wall between the seventh and tenth ribs, lateral chest wall between the sixth and ninth ribs, the dome of the diaphragm, and the mediastinal pleura. Computed tomographic (CT) findings support this distribution but also show anterior and paravertebral plaques not well shown at chest radiography. Imaging features of diffuse pleural thickening include a continuous sheet, often involving the costophrenic angles and apices, that rarely calcifies. The typical CT features of round atelectasis are of a round or oval mass that abuts the pleura, a "comet tail" of bronchovascular structures going into the mass, and thickening of the adjacent pleura. Features of asbestosis on chest radiographs include ground-glass opacification, small nodular opacities, "shaggy" cardiac silhouette, and ill-defined diaphragmatic contours. CT, however, is more sensitive in their detection. Chest radiography in patients with malignant mesothelioma may show an effusion, pleural thickening, and as the tumor progresses, a more lobulated outline. CT can help identify the disease in its early stages. Asbestos-related cancers can occur anywhere in the lungs. Recognition of the clinical, radiologic, and pathologic features of these diseases will be important for some years to come.}, } @article {pmid12365192, year = {2002}, author = {Valić, F}, title = {The asbestos dilemma: I. Assessment of risk.}, journal = {Arhiv za higijenu rada i toksikologiju}, volume = {53}, number = {2}, pages = {153-167}, pmid = {12365192}, issn = {0004-1254}, mesh = {Asbestos/*adverse effects ; Asbestos, Amphibole/adverse effects ; Asbestos, Serpentine/adverse effects ; Carcinogens/adverse effects ; Environmental Exposure ; Humans ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Risk Assessment ; }, abstract = {This paper gives a critical review of current problems related to quantitative health risk assessment of exposure to asbestos, and particularly to chrysotile, the only type of asbestos still available on the market. The paper reviews types, sources, uses and the main recognised health effects of asbestos, paying particular attention to the health-related properties of fibres and the role of their biopersistence. The main focus is on yet unresolved issues which introduce a large margin of uncertainty into the published quantitative risk assessments: 1) Are all asbestos types equally dangerous or is chrysotile asbestos less dangerous than amphiboles? 2) Are health effects of asbestos fibres threshold or non-threshold effects? 3) Are errors in mathematical modelling of risks so great as to make the risk evaluations worthless? Attention is also given to errors in estimates of past exposures, uncertainties and unspecificities of models and to the unfeasibility of practical application of some well recognized risk assessment models.}, } @article {pmid12359747, year = {2002}, author = {Bolognesi, C and Filiberti, R and Neri, M and Perrone, E and Landini, E and Canessa, PA and Simonassi, C and Cerrano, PG and Mutti, L and Puntoni, R}, title = {High frequency of micronuclei in peripheral blood lymphocytes as index of susceptibility to pleural malignant mesothelioma.}, journal = {Cancer research}, volume = {62}, number = {19}, pages = {5418-5419}, pmid = {12359747}, issn = {0008-5472}, mesh = {Asbestos/adverse effects ; Case-Control Studies ; Female ; Humans ; Lung Neoplasms/blood/genetics ; Lymphocytes/*ultrastructure ; Male ; Mesothelioma/blood/*genetics ; *Micronuclei, Chromosome-Defective ; Occupational Exposure ; Pleural Neoplasms/blood/genetics ; }, abstract = {We evaluated the frequency of micronuclei (MN) in peripheral blood lymphocytes of patients with pleural malignant mesotelioma (MM), lung cancer, benign respiratory diseases, and healthy controls. A significant increased frequency of MN was observed in patients with MM in comparison with all the other groups (median, 11.4 binucleated MN/1000 binucleated cells versus 5.1, 6.1, and 6.2, respectively). No association was found between MN and asbestos exposure. Recently, genetic susceptibility associated with asbestos exposure has been recognized in the development of MM. The presence of high frequency of MN in peripheral blood lymphocytes of patients with MM could represent a useful index of individual susceptibility to this tumor.}, } @article {pmid12354519, year = {2002}, author = {Misdorp, W}, title = {Tumours in calves: comparative aspects.}, journal = {Journal of comparative pathology}, volume = {127}, number = {2-3}, pages = {96-105}, doi = {10.1053/jcpa.2002.0563}, pmid = {12354519}, issn = {0021-9975}, mesh = {Age Distribution ; Animals ; Animals, Newborn ; Cattle ; Cattle Diseases/*pathology ; Child ; Female ; Fetal Diseases/etiology/pathology/veterinary ; Humans ; Male ; Neoplasms/etiology/pathology/*veterinary ; Species Specificity ; Swine ; }, abstract = {In this paper, calf neoplasia is discussed in relation to a series of cases comprising (1). spontaneous congenital bovine tumours of fetuses and newborn animals, (2). spontaneous juvenile-type tumours in calves aged 2-12 months, and (3). iatrogenic tumours of calves. The congenital cases (n=14) consisted of tumours of a predominantly mesenchymal and malignant nature (malignant lymphoma, mesothelioma and mixed mesodermal tumour). In the juvenile cases (n=11), malignant lymphoma and sarcoma were the commonest forms. In comparing tumour patterns in calves with those reported in adult cattle, it was apparent that tumours were less common in the former (6 versus 60 per 100000) and that, with the exception of malignant lymphoma, the types of tumour differed. Carcinomas, which were virtually absent in calves, predominated in adults, probably due to the longer exposure of older animals to carcinogenic factors. In comparing tumour patterns in calves with those reported in pigs and children, it was clear that calf cases were mainly sporadic, with the notable exception of malignant lymphoma in twins. In young pigs, however, several types of tumour (some hereditary) were reported on a single farm as multiple cases. In children, tumours occurred more frequently than in calves, and many neoplasms in both children and calves could be regarded as embryonic tumours or hamartomas. Little is known about the pathogenetic pathways of tumours in calves, with the exception of congenital neuro-fibromatosis (hereditary) and possibly of mesotheliomatosis (due to asbestos). Modern methods of analysing chromosomal and gene aberrations may be helpful in clarifying the pathogenesis of congenital tumours.}, } @article {pmid12212285, year = {1999}, author = {Luo, S and Liu, X and Wang, C and Zhu, R}, title = {[Mesothelioma in rats following-intrapleural-injection of crocidolite].}, journal = {Hua xi yi ke da xue xue bao = Journal of West China University of Medical Sciences = Huaxi yike daxue xuebao}, volume = {30}, number = {3}, pages = {286-288}, pmid = {12212285}, issn = {0257-7712}, mesh = {Animals ; Asbestos, Crocidolite/*toxicity ; Female ; Male ; Mesothelioma/*chemically induced ; Pleural Neoplasms/*chemically induced ; Random Allocation ; Rats ; Rats, Wistar ; }, abstract = {In order to investigate the potential of pleural mesothelioma induced by crocidolite, author collected samples from four county areas (Dayao, Yaoan, Muding and Yanyuan) in China. A suspension of 1 ml containing 20 mg crocidolite fiber was injected into the right pleural cavity of each rat in various test groups and UICC crocidolite group, totally 40 mg. The negative control was given saline. The results showed that the incidence of mesothelioma was 56.0%-68.8% (in which the rate of induction in Yanyuan group was the highest), and the survival time of the first case of mesothelioma was 273-347 days in the test groups, the Yanyuan group had shorter latency, and the mean survival days of the rats with mesothelioma for four groups were 560, 490, 593 and 498 days respectively; the shortest mean survival time was that for Yanyuan group. The major histological type of mesothelioma induced by crocidolite was the fibrous type. The degree of differentiation in all mesotheliomas was mainly intermediate and low. The results suggested that when rats were intrapleurally inoculated with samples of crocidolite and saline, an appreciable proportion of animals developed mesothelioma except those of the saline group. Compared with other groups, the Yanyuan group had stronger potential of crocidolite-induced mesothelioma.}, } @article {pmid12205241, year = {2002}, author = {Dumortier, P and Rey, F and Viallat, JR and Broucke, I and Boutin, C and De Vuyst, P}, title = {Chrysotile and tremolite asbestos fibres in the lungs and parietal pleura of Corsican goats.}, journal = {Occupational and environmental medicine}, volume = {59}, number = {9}, pages = {643-646}, doi = {10.1136/oem.59.9.643}, pmid = {12205241}, issn = {1351-0711}, mesh = {Animals ; Asbestos, Amphibole/*analysis ; Asbestos, Serpentine/*analysis ; Carcinogens, Environmental/analysis ; Environmental Exposure/analysis ; France ; *Goats ; *Lung ; *Pleura ; }, abstract = {BACKGROUND AND AIMS: Environmental exposures to chrysotile and tremolite from the soil cause pleural plaques and mesothelioma in northeast Corsica. Goats grazing in the contaminated areas inhale asbestos fibres. We used this natural animal model to study whether these exposures actually result in increased fibre burdens in the lungs and parietal pleura.

METHODS: Ten goats from areas with asbestos outcrops and two from other areas were slaughtered. Fibre content of lung and parietal pleural samples was determined by analytical transmission electron microscopy.

RESULTS: Both chrysotile and tremolite fibres were detected. In the exposed goats, the geometric mean concentrations of asbestos fibres longer than 1 microm were 0.27 x 10(6) fibres/g dry lung tissue and 1.8 x 10(6) fibres/g dry pleural tissue. Asbestos fibres were not detected in the lungs of the two control goats. Chrysotile fibres shorter than 5 microm were predominant in the parietal pleura. Tremolite fibres accounted for 78% and 86% of the fibres longer than 5 microm in lung and parietal pleural samples, respectively.

CONCLUSIONS: Environmental exposure in northeast Corsica results in detectable chrysotile and tremolite fibre loads in the lung and parietal pleura of adult goats. Tremolite fibres of dimensions with a high carcinogenic potency are detected in the parietal pleura.}, } @article {pmid12205234, year = {2002}, author = {Saarni, H and Pentti, J and Pukkala, E}, title = {Cancer at sea: a case-control study among male Finnish seafarers.}, journal = {Occupational and environmental medicine}, volume = {59}, number = {9}, pages = {613-619}, pmid = {12205234}, issn = {1351-0711}, mesh = {Adult ; Case-Control Studies ; Finland/epidemiology ; Humans ; Incidence ; Kidney Neoplasms/epidemiology/etiology ; Leukemia/epidemiology/etiology ; Lung Neoplasms/epidemiology/etiology ; Lymphoma/epidemiology/etiology ; Male ; Mesothelioma/epidemiology/etiology ; Middle Aged ; *Naval Medicine ; Neoplasms/epidemiology/*etiology ; Occupational Diseases/epidemiology/*etiology ; Occupational Exposure ; Odds Ratio ; Risk Factors ; }, abstract = {AIMS: To study the possible work related reasons for the increased incidence of many cancers among seafarers.

METHODS: A case-control study, nested in a cohort of all male seafarers (n = 30 940) who, according to the files of the Seamen's Pension Fund, had worked on board Finnish ships for any time during the period 1960-80. Cases of cancer of the lung, nervous system, kidney, and pancreas, leukaemia, lymphoma, and all cases histologically defined as mesotheliomas were identified from the Finnish Cancer Registry in 1967-92. The preceding numbers of years at sea in various occupational categories were collected according to the type of ship (dry cargo ship, tanker, passenger vessel, icebreaker, other vessel).

RESULTS: The incidence for lung cancer among engine crew increased with the increase in employment time, the odds ratio (OR) after three years being 1.68 (95% CI 1.17 to 2.41). The OR of lung cancer for deck officers was 0.42 (95% CI 0.29 to 0.61). Deck personnel on icebreakers had a significantly increased risk of lung cancer > or =20 years after first employment (OR 3.41, 95% CI 1.23 to 9.49). The OR for mesothelioma among engine crew with a latency of 20 years was 9.75 (95% CI 1.88 to 50.6). The OR for renal cancer among deck officers after three years employment was 2.15 (95% CI 1.14 to 4.08), but there was no increase by employment time or by latency. A rise of OR for lymphoma was detected among deck personnel on tankers, if the employment had lasted over three years (OR 2.78, 95% CI 0.98 to 7.92). The risk pattern for leukaemia was similar to that of lymphoma, the OR among deck personnel on tankers varying from 2.26 (95% CI 1.01 to 5.06) to 6.86 (95% CI 1.62 to 28.8) depending on the length of employment.

CONCLUSIONS: Results indicate that occupational exposures of deck crews on tankers add to their risk of renal cancer, leukaemia, and possibly lymphoma. Engine crews have an asbestos related risk of mesothelioma, and the engine room conditions also seem to increase risk of lung cancer.}, } @article {pmid12198911, year = {2002}, author = {Pylev, LN and Vasil'eva, LA and Krinari, GA and Bakhtin, AI and Vezentsev, AI and Zubakova, LE}, title = {[The electric properties of fiber surface and the toxicity of asbestos].}, journal = {Gigiena i sanitariia}, volume = {}, number = {3}, pages = {61-64}, pmid = {12198911}, issn = {0016-9900}, mesh = {Animals ; Asbestos/*adverse effects/*chemistry ; Electricity ; Mineral Fibers ; Neoplasms/etiology ; Rats ; Rats, Wistar ; }, abstract = {Thermal treatment, autoclaving and their combination yielded 3 samples of chrysotile-asbestos. With these, as compared with parent Type PRZh-1-50 Bazhenov chrysotile, the structure of fibers deteriorated and the number of negative discharges increased in the first two samples; the superficial structure substantially increased and the number of positive centers greatly decreased in the third sample. The ratio of positive to negative centers was less in all treated samples than that in the parent one, it decreased particularly during combined treatment. In this sample, hemolytic and mutagenic activity and cytotoxicity were substantially decreased; carcinogenic activity was greatly decreased (by 4 times) (as shown by the pleural mesothelioma indication test during intrapleural administration to rats). Thermal treatment and autoclaving insignificantly lowered the hemolytic activity and mutagenicity; carcinogenicity of these samples was much less (by 2.3 and 2 times) than that of parent chrysotile.}, } @article {pmid12197049, year = {2002}, author = {Mangone, L and Romanelli, A and Campari, C and Candela, S}, title = {[Malignant mesothelioma in Emilia-Romagna: incidence and asbestos exposure].}, journal = {Epidemiologia e prevenzione}, volume = {26}, number = {3}, pages = {124-129}, pmid = {12197049}, issn = {1120-9763}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Female ; Humans ; Incidence ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology/*etiology ; Middle Aged ; Occupational Diseases/*epidemiology/*etiology ; }, abstract = {This paper describes the activity, the sources of informations, methods and results of the "Emilia-Romagna Mesothelioma Registry" (ReM). The Registry started in 1996 and collects all cases of Malignant Mesothelioma (MM) occurring in Emilia-Romagna. 323 new cases (225 males and 98 females) have been detected during the period 1996-2001. Most cases (n = 286) concerned pleura. Other observed localizations were: peritoneum (n = 30), tunica vaginalis testis (n = 4) and pericardium (n = 3). Most of the cases were reported by the Institutes of Pathology and Occupational Health and by the Safety Services (respectively the 62% and the 18%). 87% of all the cases were histologically, 8% TC, 4% radiologically and only 1% clinically confirmed. The regional incidence rate (for 10(5) person-years, age standardized on the 1991 Italian population), has been estimated to be 1.98 in males and 0.88 in females. The highest rates were registered in Piacenza and Reggio Emilia province among men and Reggio Emilia and Ravenna province among women. 72% of cases have been classified as exposed to asbestos (64% occupationally and 8% as domestic/environmentally exposed).}, } @article {pmid12187531, year = {2002}, author = {Curin, K and Sarić, M and Strnad, M}, title = {Incidence of malignant pleural mesothelioma in coastal and continental Croatia: epidemiological study.}, journal = {Croatian medical journal}, volume = {43}, number = {4}, pages = {498-502}, pmid = {12187531}, issn = {0353-9504}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Croatia/epidemiology ; Environmental Exposure ; Female ; Humans ; Incidence ; Male ; Mesothelioma/chemically induced/*epidemiology ; Middle Aged ; Occupational Exposure ; Pleural Neoplasms/chemically induced/*epidemiology ; Registries ; Surveys and Questionnaires ; }, abstract = {AIM: To evaluate the actual incidence of malignant pleural mesothelioma in Croatia, geographical distribution of the disease, and relevance of occupation and some other characteristics of diseased subjects.

METHOD: Data on the incidence of pleural mesothelioma over a seven-year period (1991-1997) were collected from the Croatian Cancer Registry. In each case, the tumor diagnosis was histologically verified. Registration of the patients was based on their place of residence. Also, in 2001, a short questionnaire was sent to patients' families to gather additional information on patients' occupation (exposure to asbestos), smoking habits, and length of residence in the registered place. In many cases some of the answers had to be clarified by telephone or through a personal contact. Data obtained from 20 counties (administrative units) of Croatia were grouped into two larger areas: coastal and continental. The data for the city of Zagreb were presented separately.

RESULTS: During the 1991-1997 period, the Registry recorded a total of 248 malignant pleural mesotheliomas (197 in men and 51 in women). The poll gathered additional data for 194 patients (78.2%): 153 (77.7%) men and 41 (80.4%) women. Eight in a million people on average were diagnosed with malignant pleural mesothelioma per year. Age standardized incidence rates (per 100,000) by residence showed an uneven geographical distribution for men: 2.66 in coastal area, 0.69 in continental area, and 0.75 in the city of Zagreb. Goodness-of-fit test for observed rates vs expected for Croatia were chi-square=145, df=2, p<0.001; post-hoc tests: coastal vs continental area chi-square=12.3, df=1, p=0.001; and coastal area vs city of Zagreb chi-square=4.4, df=1, p=0.035. In women with mesothelioma, these rates were 0.38, 0.24, and 0.18, respectively, and the differences were not statistically significant.

CONCLUSION: Assuming that the information obtained by the poll on the occupation of diseased subjects was a true characterization of all recorded cases of pleural mesothelioma, more than two-thirds of subjects with the studied tumor had an occupational exposure to asbestos. Uneven distribution of the tumor, with higher rate in men in the coastal area, may be related to shipbuilding and other industrial sources of asbestos exposure in that part of the country.}, } @article {pmid12176766, year = {2002}, author = {Berry, G}, title = {Asbestos lung fibre analysis in the United Kingdom, 1976-96.}, journal = {The Annals of occupational hygiene}, volume = {46}, number = {6}, pages = {523-526}, doi = {10.1093/annhyg/mef066}, pmid = {12176766}, issn = {0003-4878}, mesh = {*Asbestos/chemistry ; Humans ; Lung/chemistry ; Lung Neoplasms/chemistry ; Mesothelioma/epidemiology ; Mineral Fibers ; *Occupational Health ; United Kingdom/epidemiology ; }, abstract = {OBJECTIVES: To summarize data on changes in lung contents of asbestos types between 1976-77 and 1990-96 for mesotheliomas and controls in the UK.

METHODS: Data were extracted from published studies of the years 1976, 1977 and 1990-96.

RESULTS: Between 1976-77 and 1990-96 there was a large reduction in the amount of crocidolite in the lungs of both mesotheliomas and controls.

CONCLUSION: The results are consistent with the use of the different asbestos types in the UK, after taking into account the period of exposure and elimination of fibres from the lung in the time elapsed since exposure.}, } @article {pmid12176759, year = {2002}, author = {Roggli, VL and Vollmer, RT and Butnor, KJ and Sporn, TA}, title = {Tremolite and mesothelioma.}, journal = {The Annals of occupational hygiene}, volume = {46}, number = {5}, pages = {447-453}, pmid = {12176759}, issn = {0003-4878}, mesh = {Aged ; Asbestos, Amphibole/*adverse effects ; Female ; Humans ; Male ; Mesothelioma/*etiology ; Middle Aged ; Occupational Diseases/*etiology ; Occupational Exposure/*analysis ; }, abstract = {BACKGROUND: Exposure to chrysotile dust has been associated with the development of mesothelioma and recent studies have implicated contaminating tremolite fibers as the likely etiological factor. Tremolite also contaminates talc, the most common non-asbestos mineral fiber in our control cases.

METHODS: We examined 312 cases of mesothelioma for which fiber burden analyses of lung parenchyma had been performed by means of scanning electron microscopy to determine the content of tremolite, non-commercial amphiboles, talc and chrysotile. The vast majority of these patients were exposed to dust from products containing asbestos.

RESULTS: Tremolite was identified in 166 of 312 cases (53%) and was increased above background levels in 81 cases (26%). Fibrous talc was identified in 193 cases (62%) and correlated strongly with the tremolite content (P < 0.0001). Chrysotile was identified in only 32 cases (10%), but still correlated strongly with the tremolite content (P < 0.0001). Talc levels explained less of the tremolite deviance for cases with an increased tremolite level than for cases with a normal range tremolite level (22 versus 42%). In 14 cases (4.5%) non-commercial amphibole fibers (tremolite, actinolite and/or anthophyllite) were the only fiber types found above background.

CONCLUSIONS: We conclude that tremolite in lung tissue samples from mesothelioma victims derives from both talc and chrysotile and that tremolite accounts for a considerable fraction of the excess fiber burden in end-users of asbestos products.}, } @article {pmid12173377, year = {2002}, author = {Kottek, M and Kilpatrick, D}, title = {Re: Malignant mesothelioma from neighborhood exposure to anthophyllite asbestos.}, journal = {American journal of industrial medicine}, volume = {41}, number = {6}, pages = {514}, doi = {10.1002/ajim.10071}, pmid = {12173377}, issn = {0271-3586}, mesh = {Asbestos, Amphibole/*adverse effects ; Environmental Exposure/*analysis ; Humans ; Mesothelioma/epidemiology/*etiology ; Mining ; Residence Characteristics ; Western Australia/epidemiology ; }, } @article {pmid12170312, year = {2002}, author = {Furalev, VA and Kravchenko, IV and Vasil'eva, LA and Pylev, LN}, title = {Cytotoxic effects of macrophages and asbestos on transformed rat mesothelial cells.}, journal = {Bulletin of experimental biology and medicine}, volume = {133}, number = {1}, pages = {71-73}, doi = {10.1023/a:1015116830012}, pmid = {12170312}, issn = {0007-4888}, mesh = {Animals ; Asbestos/*adverse effects ; Cell Transformation, Neoplastic ; Cells, Cultured ; Coculture Techniques ; Culture Media ; Genes, ras ; Humans ; Macrophages, Peritoneal/*metabolism ; Neoplasms, Mesothelial/etiology/*pathology ; Pleura/pathology ; Rats ; Rats, Wistar ; }, abstract = {Asbestos produced a cytotoxic effect on transformed cells of rat pleural mesothelium and on IAR2 epithelial cells and Rat1 fibroblasts transformed by ras oncogene, but not on normal cells of these strains under conditions of coculturing with peritoneal macrophages. Contact of mesothelioma cells, but not macrophages with asbestos was necessary and sufficient for attaining the cytotoxic effect. Macrophage-conditioned medium potentiated asbestos cytotoxicity for transformed mesothelial cells, but not for IARS-ras and Rat1-ras.}, } @article {pmid12168054, year = {2002}, author = {Pylkkänen, L and Sainio, M and Ollikainen, T and Mattson, K and Nordling, S and Carpén, O and Linnainmaa, K and Husgafvel-Pursiainen, K}, title = {Concurrent LOH at multiple loci in human malignant mesothelioma with preferential loss of NF2 gene region.}, journal = {Oncology reports}, volume = {9}, number = {5}, pages = {955-959}, pmid = {12168054}, issn = {1021-335X}, mesh = {Alleles ; Biomarkers, Tumor ; Humans ; Immunoblotting ; *Loss of Heterozygosity ; Mesothelioma/*genetics ; Microsatellite Repeats ; Neurofibromin 2/*genetics ; Pleural Neoplasms/*genetics ; Polymerase Chain Reaction ; Tumor Cells, Cultured ; }, abstract = {Human malignant mesothelioma (MM) is a highly aggressive neoplasm related to occupational asbestos exposure and characterised by a long latency period between the exposure and onset of disease. Previous studies indicate that losses at different genomic regions are present in MM. We examined allele loss at three known tumour suppressor gene regions (22q/NF2 gene, 9p/p16 gene, and 3p/FHIT gene) and at two other frequently deleted areas (14q and 6q) in MM. Loss of heterozygosity (LOH) was investigated in cell cultures and primary tumours with several highly polymorphic markers for each site. To study if LOH of the NF2 gene is a consistent feature in MM, we performed a more detailed analysis of chromosome 22q that included a NF2 marker (NF2CA3). We observed a high frequency of LOH occurring simultaneously at multiple loci. In particular, 100% of the cultured MM cells exhibited LOH at the NF2 gene region. From the other chromosomal sites analysed, recurrent allele loss was detected at 9p (5/7; 71%), 3p (4/7; 57%), 14q (3/7; 43%), and 6q (3/7; 43%). Of the 32 tumours, even those trimmed to exclude normal tissue, few showed LOH, suggesting consielment by normal cells within MM tumours, whereas tumour cells in primary cultures showed LOH already in passages 1-2. In conclusion, our present LOH data indicate that MM cells exhibit allele losses at multiple tumour suppressor gene sites concurrently, involving NF2 gene preferentially. This supports the view that the accumulation of multiple genetic hits is characteristic to malignant transformation of MM cells.}, } @article {pmid12167211, year = {2002}, author = {Dodson, RF and Williams, MG and Satterley, JD}, title = {Asbestos burden in two cases of mesothelioma where the work history included manufacturing of cigarette filters.}, journal = {Journal of toxicology and environmental health. Part A}, volume = {65}, number = {16}, pages = {1109-1120}, doi = {10.1080/152873902760125354}, pmid = {12167211}, issn = {1528-7394}, mesh = {Aged ; Asbestos, Crocidolite/*adverse effects ; Fatal Outcome ; Humans ; Male ; Mesothelioma/*etiology/pathology ; Occupational Exposure ; Pleural Neoplasms/*etiology/pathology ; *Tobacco Industry ; }, abstract = {Asbestos has been used in many applications, but possibly one of the more unique was in the manufacturing of filters for cigarettes. The type of asbestos used in this application was crocidolite. Data from several resources indicate that crocidolite was one of the least utilized types of commercial asbestos in the United States. The present study provides quantitative tissue burden analysis data for two mesothelioma cases where the work histories included manufacturing of cigarette filters that contained crocidolite. The data include the number of asbestos bodies and uncoated fibers per gram of tissue, as well as the dimensions of these structures. The conclusion of the findings indicates that the individuals had an appreciable homogeneous exposure to crocidolite asbestos.}, } @article {pmid12164558, year = {2002}, author = {Zellos, LS and Sugarbaker, DJ}, title = {Diffuse malignant mesothelioma of the pleural space and its management.}, journal = {Oncology (Williston Park, N.Y.)}, volume = {16}, number = {7}, pages = {907-13; discussion 916-7, 919-20, 925}, pmid = {12164558}, issn = {0890-9091}, mesh = {Aged ; Chemotherapy, Adjuvant ; Combined Modality Therapy ; Female ; Humans ; Male ; Mesothelioma/*pathology/*therapy ; Middle Aged ; Neoplasm Invasiveness ; Pleural Neoplasms/*pathology/*therapy ; Prognosis ; Radiotherapy, Adjuvant ; Survival ; }, abstract = {Diffuse malignant pleural mesothelioma is a rare and aggressive malignancy of the pleura that is usually caused by exposure to asbestos. Between 2,000 and 3,000 new cases are expected to be diagnosed annually in the United States. Difficulties in diagnosis, staging, and treatment set this disease apartfrom other malignancies. The variable clinical presentation and problems in establishing a definite histopathologic diagnosis result in significant delays in treatment. Three histologic subtypes of the disease are described in this review: epithelial, sarcomatous, and mixed histologies. The Butchart, International Mesothelioma Interest Group, and Brigham staging systems are the most commonly used staging systems. The disease's natural history involves aggressive local growth, invasion of vital mediastinal structures, and death within 4 to 12 months without treatment. Single-modality therapy of any kind has failed to substantially alter this natural history. Aggressive, multimodality regimens that include surgery, radiation, and chemotherapy have resulted in improved survival in properly selected patients. However, innovative therapies are still needed to prolong survival in patients with early and advanced disease.}, } @article {pmid12154012, year = {2002}, author = {Manning, CB and Cummins, AB and Jung, MW and Berlanger, I and Timblin, CR and Palmer, C and Taatjes, DJ and Hemenway, D and Vacek, P and Mossman, BT}, title = {A mutant epidermal growth factor receptor targeted to lung epithelium inhibits asbestos-induced proliferation and proto-oncogene expression.}, journal = {Cancer research}, volume = {62}, number = {15}, pages = {4169-4175}, pmid = {12154012}, issn = {0008-5472}, support = {ES/HL09213/ES/NIEHS NIH HHS/United States ; T32 ES07122/ES/NIEHS NIH HHS/United States ; }, mesh = {Administration, Inhalation ; Animals ; Asbestos, Crocidolite/*toxicity ; Cell Division/drug effects/physiology ; Epithelial Cells/drug effects/pathology ; ErbB Receptors/biosynthesis/genetics/metabolism/*physiology ; Female ; Gene Expression Regulation/drug effects/physiology ; Genes, fos/drug effects ; Genes, jun/drug effects ; Lung/*drug effects/metabolism/pathology/physiology ; Male ; Mice ; Mice, Transgenic ; Mitogen-Activated Protein Kinase Kinases/metabolism ; Mutation ; Phosphorylation ; Pneumonia/chemically induced/metabolism/pathology ; Proto-Oncogene Mas ; Proto-Oncogene Proteins c-fos/*biosynthesis/genetics ; Proto-Oncogene Proteins c-jun/*biosynthesis/genetics ; Signal Transduction/drug effects/physiology ; }, abstract = {Asbestos is a ubiquitous naturally occurring fiber causing multiple cancers and fibroproliferativedisease. The mechanisms of epithelial cell hyperplasia, a hallmark of the initiation of lung cancers by asbestos, have been unclear. We demonstrate here that mice expressing a dominant-negative mutant epidermal growth factor receptor (EGFR) under the control of the human lung surfactant protein-C promoter exhibit decreased pulmonary epithelial cell proliferation without alterations in asbestos-induced inflammation. In contrast to transgene-negative littermates, inhalation of asbestos by mice expressing the mutant EGFR does not result in early and elevated expression of early response proto-oncogenes (fos/jun or activator protein 1 family members). Additionally, quantitative reverse transcriptase-PCR analysis for levels of c-jun and c-fos in bronchiolar epithelium isolated by laser capture microdissection demonstrates increases in expression of these genes in asbestos-exposed epithelial cells. Results show that the EGFR mediates both asbestos-induced proto-oncogene expression and epithelial cell proliferation, providing a rationale for modification of its phosphorylation in preventive and therapeutic approaches to lung cancers and mesothelioma.}, } @article {pmid12151629, year = {2002}, author = {Vaslet, CA and Messier, NJ and Kane, AB}, title = {Accelerated progression of asbestos-induced mesotheliomas in heterozygous p53+/- mice.}, journal = {Toxicological sciences : an official journal of the Society of Toxicology}, volume = {68}, number = {2}, pages = {331-338}, doi = {10.1093/toxsci/68.2.331}, pmid = {12151629}, issn = {1096-6080}, support = {R01 ES03721/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Apoptosis/drug effects ; Asbestos, Crocidolite/administration & dosage/*toxicity ; DNA, Neoplasm/analysis ; Disease Progression ; Genes, p53/*genetics ; Heterozygote ; In Situ Nick-End Labeling ; Injections, Intraperitoneal ; Loss of Heterozygosity ; Male ; Mesothelioma/*chemically induced/genetics/pathology ; Mice ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Micronuclei, Chromosome-Defective/drug effects ; Neoplasm Invasiveness ; Peritoneal Neoplasms/*chemically induced/genetics/pathology ; Pleural Neoplasms/*chemically induced/genetics/pathology ; Tumor Cells, Cultured ; }, abstract = {Asbestos fibers produce diffuse malignant mesotheliomas in chronic rodent inhalation assays or after direct intrapleural or intraperitoneal injection. In vitro models have provided evidence that asbestos fibers are genotoxic carcinogens that can directly or indirectly generate reactive oxygen- and nitrogen-derived species that cause DNA damage. Heterozygous p53+/- mice show an increased incidence and reduced latency of malignant mesotheliomas induced by weekly intraperitoneal injections of crocidolite asbestos fibers. In this study, we investigated whether loss of heterozygosity (LOH) at the p53 tumor-suppressor gene locus contributes to accelerated tumor progression. LOH was found in 50% of the tumors produced in heterozygous p53+/- mice. In contrast to tumors that arise in p53+/+ mice or those that retained one p53 allele, LOH was associated with large tumor masses with central areas of necrosis, local invasion, and penetration of lymphatics. Increased tumor size was not associated with increased levels of cell proliferation as determined by BrdU incorporation, but it was correlated with a reduction in apoptosis as determined morphologically and by the TUNEL assay. Wild-type p53 protein is essential for cell cycle arrest in response to DNA damage and in maintenance of genomic stability. Cell lines established from tumors that showed LOH at the p53 tumor-suppressor gene locus were nearly tetraploid. These results suggest that p53 haplo-insufficiency sensitizes mice to the clastogenic or aneuploidogenic effects of crocidolite asbestos fibers, resulting in a shorter latent period. As solid tumors develop, spontaneous loss of the wild-type allele accompanied by decreased apoptosis and genetic instability is associated with accelerated tumor growth, invasion, and lymphatic dissemination.}, } @article {pmid12142203, year = {2002}, author = {Aziz, T and Jilaihawi, A and Prakash, D}, title = {The management of malignant pleural mesothelioma; single centre experience in 10 years.}, journal = {European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery}, volume = {22}, number = {2}, pages = {298-305}, doi = {10.1016/s1010-7940(02)00273-7}, pmid = {12142203}, issn = {1010-7940}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Mesothelioma/*therapy ; Middle Aged ; Pleural Neoplasms/*therapy ; Retrospective Studies ; Survival Analysis ; Treatment Outcome ; }, abstract = {BACKGROUND AND OBJECTIVES: Malignant pleural mesothelioma (MPM) is an asbestos-related disease of the pleura with a survival time without treatment ranging from 4 to 12 months. The objective of this study is to review our experience in selection of MPM patients for various modalities of treatment.

METHODS: Between 1989 and 1998, 302 patients with MPM have been referred to our Centre for assessment. Majority (191 patients, 61%) of them received no specific treatment. Forty-seven patients were treated by decortication/pleurectomy and 64 had a radical extra-pleural pneumonectomy (EPP). Intrapleural chemotherapy and systemic post-operative chemotherapy was employed only in the last 51 patients following radical surgery.

RESULTS: The average survival was 8.9 months for those treated by palliative care only. The average survival was 13 and 14 months for patients treated by radical surgery only or by decortication/pleurectomy, respectively. However, survival has improved to a mean of 35 months for patients treated by radical surgery followed by systemic post-operative chemotherapy. In this group, the survival prevalence was 90 and 70% for T1 patients and 85 and 36% for T2 patients at 1 and 3 years, respectively (P=0.002). Survival was surprisingly, not affected by lymph node involvement (P=0.08) or pathological type of MPM (P=0.07). The operative mortality was 9% for EPP and 0% for decortication/pleurectomy.

CONCLUSION: In selected patients with MPM, complete surgical resection by EPP represents an important initial step in their management. Systemic chemotherapy improves survival in surgically treated patients. Further trials are needed to improve on the adjuvant treatment regimes.}, } @article {pmid12136076, year = {2002}, author = {Baser, ME and De Rienzo, A and Altomare, D and Balsara, BR and Hedrick, NM and Gutmann, DH and Pitts, LH and Jackler, RK and Testa, JR}, title = {Neurofibromatosis 2 and malignant mesothelioma.}, journal = {Neurology}, volume = {59}, number = {2}, pages = {290-291}, doi = {10.1212/wnl.59.2.290}, pmid = {12136076}, issn = {0028-3878}, support = {P30 CA006927/CA/NCI NIH HHS/United States ; R01 CA045745/CA/NCI NIH HHS/United States ; CA-45745/CA/NCI NIH HHS/United States ; NS-35848/NS/NINDS NIH HHS/United States ; }, mesh = {Adult ; Fatal Outcome ; Humans ; Immunohistochemistry ; Male ; Mesothelioma/*complications/*diagnosis/pathology ; Neurofibromatosis 2/*complications/*diagnosis/pathology ; Neurofibromin 2/immunology ; Peritoneal Neoplasms/*complications/*diagnosis/pathology ; }, abstract = {Mutations of the neurofibromatosis 2 (NF2) tumor suppressor gene cause the inherited disorder NF2 and are also common in malignant mesothelioma, which is not a characteristic feature of NF2. The authors report an asbestos-exposed person with NF2 and malignant mesothelioma. Immunohistochemical analysis of the mesothelioma confirmed loss of expression of the NF2 protein, and comparative genomic hybridization revealed losses of chromosomes 14, 15, and 22, and gain of 7. The authors propose that a person with a constitutional mutation of an NF2 allele is more susceptible to mesothelioma.}, } @article {pmid12122570, year = {2002}, author = {Cullen, RT and Miller, BG and Clark, S and Davis, JM}, title = {Tumorigenicity of cellulose fibers injected into the rat peritoneal cavity.}, journal = {Inhalation toxicology}, volume = {14}, number = {7}, pages = {685-703}, doi = {10.1080/08958370290084584}, pmid = {12122570}, issn = {0895-8378}, mesh = {Air Pollutants, Occupational/toxicity ; Animals ; Asbestos, Crocidolite/toxicity ; Carcinogenicity Tests ; Carcinogens/*toxicity ; Cellulose/*toxicity ; Dose-Response Relationship, Drug ; Injections, Intraperitoneal ; Male ; Maximum Tolerated Dose ; Mesothelioma/etiology ; Mineral Fibers/toxicity ; Particle Size ; Peritoneal Neoplasms/*etiology ; Pleural Neoplasms/etiology ; Rats ; Rats, Wistar ; Sarcoma, Experimental/*etiology ; }, abstract = {Cellulose fibers, along with many other organic fibers, are durable. Therefore, if inhaled, they have the potential to persist within the lung, and may then cause disease. Here we report the effects of injecting high-purity cellulose fibers into the abdominal cavity of rats. A respirable fraction of cellulose fiber was collected from an aerosol of a thermo-mechanically-processed wood pulp. A sample of respirable crocidolite asbestos, known to produce mesotheliomas in rats, was used as a positive control. Total doses of 10(6), 10(7), 10(8), or 10(9) WHO fibers were injected intraperitoneally as 3 weekly aliquots. A negative control was provided by phosphate-buffered saline used to suspend the fibers for injection. There were 50 rats per treatment group except for the 10(8) and 10(9) fibers crocidolite groups which were reduced to 26 rats because of the expectation of high tumor incidence in these groups. The two higher doses of crocidolite asbestos caused greatly reduced survival compared to the saline controls. With cellulose there was a much less marked effect on survival. In the highest dose cellulose group, multiple large nodules (granulomas) and widespread adhesions (bands of new tissue connecting organs to each other and to the abdominal wall) were present in all animals. Granulomas were not observed in the 10(9) fibers crocidolite group. More than 80% of animals in the 10(8) and 10(9) crocidolite asbestos groups had mesotheliomas, a type of tumor sometimes observed in people exposed to asbestos. In contrast, there were only 2 animals in the cellulose groups with mesothelioma tumors, 1 in the 10(7) and 1 in the 10(8) groups. However, 9 (18%) of the 10(9) cellulose group had malignant tumors that, in contrast to the usual pattern of mesothelioma development following treatment with mineral fibers in rats, showed no obvious involvement of mesothelial tissues, were not associated with blood-stained ascites fluid, and were thus classified as sarcomas. This study has demonstrated that a high dose of cellulose fibers is capable of producing tumors when injected into the abdominal cavity of rats.}, } @article {pmid12121236, year = {2002}, author = {Attanoos, RL and Galateau-Salle, F and Gibbs, AR and Muller, S and Ghandour, F and Dojcinov, SD}, title = {Primary thymic epithelial tumours of the pleura mimicking malignant mesothelioma.}, journal = {Histopathology}, volume = {41}, number = {1}, pages = {42-49}, doi = {10.1046/j.1365-2559.2002.01422.x}, pmid = {12121236}, issn = {0309-0167}, mesh = {Adult ; Aged ; *Biomarkers, Tumor ; Calbindin 2 ; Diagnosis, Differential ; Female ; Humans ; Keratins/metabolism ; Male ; Mediastinum ; Mesothelioma/metabolism/pathology ; Middle Aged ; Neoplasms, Glandular and Epithelial/metabolism/*pathology ; Neoplasms, Mesothelial/metabolism/pathology ; Pleural Neoplasms/*metabolism/*pathology ; S100 Calcium Binding Protein G/metabolism ; Thrombomodulin/metabolism ; Thymus Neoplasms/*metabolism/*pathology ; }, abstract = {AIMS: To illustrate the macroscopic, light microscopic and immunophenotypic similarities that exist between primary pleural thymic epithelial tumours and diffuse malignant mesothelioma. To investigate the expression of the mesothelial markers, cytokeratin (CK) 5/6, calretinin and thrombomodulin in a series of mediastinal thymic epithelial tumours.

METHODS AND RESULTS: Over a 10-year period, 64 diffuse pleural tumours of non-mesothelial histogenesis were identified in the files of referrals to the South Wales regional thoracic centre (Llandough Hospital, Cardiff). Of these, five pleural tumours were diagnosed as primary pleural thymic epithelial neoplasms. From the files of the Mesopath group, Caen, three additional cases of thymic epithelial tumours with pleural involvement were identified. The study group comprised eight cases (four males, four females) with median age at presentation of 56 years (range 19-75 years). In one case there was a history of asbestos exposure. Macroscopically, seven tumours formed diffuse pleural masses. No mediastinal abnormality or intraparenchymal lesions were seen in five cases. By light microscopy, seven thymic epithelial neoplasms showed a lobulated architecture, one appeared extensively cystic. The tumours were of varied morphological subtypes: one medullary (WHO Type A), two mixed (WHO Type AB), three predominantly cortical (WHO Type B1) and two cortical (WHO Type B1). The subtypes morphologically mimicked sarcomatoid, biphasic, lymphohistiocytoid variant and epithelioid mesothelioma. The pleural thymic epithelial tumours showed immunoreactivity with broad spectrum cytokeratin AE1/AE3 (8/8; 100%), CK5/6 (8/8; 100%), and 1/8 (13%) expressed thrombomodulin. Calretinin showed variable nuclear and cytoplasmic expression in all cases, but equivocally in the thymic epithelial cell component. In 7/8 (88%) the thymic epithelial cells exhibited focal aberrant expression of CD20. Epithelial membrane antigen (EMA) showed focal expression in the perivascular and organoid areas in 6/8 (75%) cases. Carcinoembryonic antigen (CEA) and CD34 were uniformly negative. In 4/8 (50%) cases the lymphoid cell component was of immature phenotype expressing CD99, terminal deoxynucleotidyl transferase (TdT) and lymphoid precursors had a high proliferation fraction with Ki67. In the series of 20 primary mediastinal thymic epithelial tumours tested, mesothelial marker expression revealed CK5/6 (20/20), thrombomodulin (3/20; 15%) and calretinin (0/20; 0%). Varying amounts of calretinin-positive stromal cells were present.

CONCLUSION: Primary pleural thymic epithelial tumours are rare but may mimic malignant mesothelioma by forming diffuse serosal-based masses. In addition, both tumours may show morphological diversity (with epithelial, spindled and mixed components present). An awareness that thymic epithelial tumours may variably express the mesothelial markers CK5/6, calretinin and thrombomodulin prevents misdiagnosis. In the distinction from malignant mesothelioma a lobulated architecture and organoid features favour a thymic epithelial neoplasm. The presence of aberrant CD20 expression in a cytokeratin-positive epithelial neoplasm and/or the presence of an immature lymphoid population (by demonstration of CD1a, CD2, CD99 and TdT) indicates a thymic epithelial neoplasm. In contrast, nuclear calretinin expression favours malignant mesothelioma.}, } @article {pmid12117769, year = {2002}, author = {Hirao, T and Bueno, R and Chen, CJ and Gordon, GJ and Heilig, E and Kelsey, KT}, title = {Alterations of the p16(INK4) locus in human malignant mesothelial tumors.}, journal = {Carcinogenesis}, volume = {23}, number = {7}, pages = {1127-1130}, doi = {10.1093/carcin/23.7.1127}, pmid = {12117769}, issn = {0143-3334}, support = {CA 78609/CA/NCI NIH HHS/United States ; ES 00002/ES/NIEHS NIH HHS/United States ; ES 06717/ES/NIEHS NIH HHS/United States ; }, mesh = {Adult ; Aged ; Cyclin-Dependent Kinase Inhibitor p16/*genetics/metabolism ; DNA Methylation ; DNA Mutational Analysis ; DNA Primers/chemistry ; DNA, Neoplasm/analysis ; Female ; Gene Deletion ; Gene Expression ; Gene Silencing ; Humans ; Male ; Mesothelioma/*genetics/pathology ; Middle Aged ; Neoplasms, Mesothelial/*genetics/pathology ; RNA, Messenger/metabolism ; Retinoblastoma Protein/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Transfection ; Tumor Cells, Cultured ; Tumor Suppressor Protein p14ARF/genetics/metabolism ; Tumor Suppressor Protein p53/genetics ; }, abstract = {The INK4 locus has two promoters and encodes two unique proteins that share exons in different reading frames, p16(INK4a) and p14(ARF). The p16(INK4a) protein, by inhibiting cyclin-dependent kinase, down regulates Rb-E2F and leads to cell cycle arrest in the G1 phase. The p14(ARF) protein interacts with the MDM2 protein, neutralizing MDM2-mediated degradation of p53. Since p53/Rb genes are not altered in malignant mesothelioma, additional components of these pathways, such as p16(INK4a) and p14(ARF), are candidates for inactivation. In this study, we have examined p16(INK4a) and p14(ARF) alterations (gene deletion, mutation and promoter methylation) in 45 primary malignant mesothelioma specimens. Fourteen patients (31%) had altered p16; four tumors had a methylated promoter region (8.8%), 10 tumors showed p16 to be deleted (22.2%), and one tumor had a point mutation (2%). We did not find any instances of methylation in the p14(ARF) 5'-CpG island. Patients whose tumors had p16 deletion were significantly younger than those with methylation, and, in the patients whose lungs were studied for the prevalence of asbestos fibers, those with any p16 alteration had lower fiber counts than those with no p16 alteration. Hence, p16 gene alteration is relatively common in malignant mesothelioma, while p14(ARF) is rarely, if ever, methylated. Our data suggest that deletion of p16 occurs in a relatively susceptible subset of the population.}, } @article {pmid12097771, year = {2002}, author = {Müller, KM and Schmitz, I and Konstantinidis, K}, title = {Black spots of the parietal pleura: morphology and formal pathogenesis.}, journal = {Respiration; international review of thoracic diseases}, volume = {69}, number = {3}, pages = {261-267}, doi = {10.1159/000063630}, pmid = {12097771}, issn = {0025-7931}, mesh = {*Dust ; Fibrosis ; Foreign Bodies/*pathology ; Humans ; Immunohistochemistry ; Mesothelioma/pathology ; Pleura/*pathology ; Pleural Neoplasms/pathology ; }, abstract = {BACKGROUND: Dark incorporations (black spots) have been described in various organs. 'Black spots' seen as flat-to-nodular lesions of the parietal pleura are common findings in former miners. They represent areas of coal dust accumulation. An increased incorporation of asbestos fibres has been described in these areas, causing them to be seen as potential starting points for malignant mesotheliomas.

OBJECTIVES: The aim of our examinations was to describe the morphology of black spots in order to understand their formal pathogenesis and discuss their role in the development of malignant mesotheliomas.

MATERIALS: We report the results of the morphological and energy dispersive X-ray analysis of 12 black spots (4 surgical and 8 autopsy specimens) located in the parietal pleura.

RESULTS: Black spots of the pleura develop in close correlation to lymphatic channels and blood vessels. Their formal pathogenesis is characterized by a mild fibrosis and an inflammatory reaction to the incorporated foreign particles. The proliferation of connective tissue may result in the formation of hyaline granulomas. Aluminum, silicone and sometimes fibres are also found in such areas. Mesothelial cells may be irritated.

CONCLUSION: Although there are hints for an increased proliferation of mesothelial cells in some areas with black spots, our findings do not support the classification of black spots as an obligate early lesion in the development of malignant mesotheliomas.}, } @article {pmid12082623, year = {2002}, author = {Toyooka, S and Carbone, M and Toyooka, KO and Bocchetta, M and Shivapurkar, N and Minna, JD and Gazdar, AF}, title = {Progressive aberrant methylation of the RASSF1A gene in simian virus 40 infected human mesothelial cells.}, journal = {Oncogene}, volume = {21}, number = {27}, pages = {4340-4344}, doi = {10.1038/sj.onc.1205381}, pmid = {12082623}, issn = {0950-9232}, support = {5U01CA8497102/CA/NCI NIH HHS/United States ; P50CA70907/CA/NCI NIH HHS/United States ; R01 CA 71618/CA/NCI NIH HHS/United States ; R01 CA2657/CA/NCI NIH HHS/United States ; }, mesh = {Alleles ; Azacitidine/*analogs & derivatives/pharmacology ; Cell Line, Transformed ; Cell Transformation, Viral/*genetics ; *Cocarcinogenesis ; CpG Islands ; *DNA Methylation/drug effects ; DNA, Neoplasm/chemistry/genetics ; Decitabine ; Gene Expression Regulation/drug effects ; *Gene Silencing ; *Genes, Tumor Suppressor ; Humans ; Hydroxamic Acids/pharmacology ; Mesothelioma/*genetics/virology ; Neoplasm Proteins/*genetics/physiology ; Polymerase Chain Reaction ; Promoter Regions, Genetic ; Simian virus 40/pathogenicity/*physiology ; *Tumor Suppressor Proteins ; }, abstract = {Mesotheliomas are tumors arising from mesothelial cells and are associated with asbestos exposure and approximately 50% contain simian virus 40 (SV40) DNA sequences. SV40 infection of human mesothelial cells (HM) causes early cellular immortalization and late transformation. Aberrant methylation is a major mech-anism for loss of function of tumor suppressor genes (TSGs). We recently reported that of seven genes frequently methylated in epithelial tumors, only RASSF1A gene was frequently methylated in mesotheliomas, and its methylation was correlated with loss of RASSF1A expression and the presence of SV40. We studied whether SV40 infection of normal HM induces aberrant methylation of the genes previously studied in mesotheliomas. Of six infected foci examined at early passages (passages 8-30) there was no methylation of the seven genes examined. Of two foci examined at late passages (passages 51-86) after the appearance of morphological changes suggestive of transformation, methylation and loss of expression of RASSF1A was detected. Sequencing of the CpG dense region around the transcription start site and semi-quantitative real-time methylation specific PCR (MSP) assay for RASSF1A methylation demonstrated progressive methylation during late passages. Exposure to the demethylating agent 5-aza-2'-deoxycytidine restored RASSF1A expression, while exposure to the histone deacetylation inhibitor trichostatin A had no effect. These data, together with our previous findings, support a causal relationship between SV40 infection, progressive RASSF1A methylation and its silencing, and the pathogenesis of mesothelioma.}, } @article {pmid12082371, year = {2002}, author = {Garg, K and Lynch, DA}, title = {Imaging of thoracic occupational and environmental malignancies.}, journal = {Journal of thoracic imaging}, volume = {17}, number = {3}, pages = {198-210}, doi = {10.1097/00005382-200207000-00004}, pmid = {12082371}, issn = {0883-5993}, mesh = {Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Carcinogens, Environmental/*adverse effects ; Carcinoma, Bronchogenic/diagnostic imaging ; Diagnosis, Differential ; Fluorodeoxyglucose F18 ; Humans ; Lung Neoplasms/*diagnostic imaging/*pathology ; Magnetic Resonance Imaging ; Male ; Mesothelioma/*diagnostic imaging/*pathology ; Middle Aged ; Mortality ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Occupational Diseases/*diagnostic imaging ; Pulmonary Atelectasis/diagnostic imaging ; Radiography ; Silicosis/diagnostic imaging ; Tomography Scanners, X-Ray Computed ; Tomography, Emission-Computed ; }, abstract = {The imaging features of occupational lung cancer are similar to those of nonoccupational cancer. Occupational lung cancer in patients with asbestos exposure must be differentiated from mimics such as round atelectasis and fissural pleural plaques. Mesothelioma remains a largely incurable tumor, though treatment options are expanding. CT, MRI, and PET scanning may all have complementary roles in staging mesothelioma.}, } @article {pmid12082370, year = {2002}, author = {Gottschall, EB}, title = {Occupational and environmental thoracic malignancies.}, journal = {Journal of thoracic imaging}, volume = {17}, number = {3}, pages = {189-197}, doi = {10.1097/00005382-200207000-00003}, pmid = {12082370}, issn = {0883-5993}, mesh = {Carcinogens/classification ; Carcinogens, Environmental/classification ; Female ; Humans ; Lung/pathology ; Lung Neoplasms/*diagnosis/*etiology ; Male ; Mesothelioma/*diagnosis/*etiology ; Occupational Diseases/*diagnosis/*etiology ; }, abstract = {Lung cancer is the most common thoracic malignancy caused by exposures at work and in the environment. The most unique thoracic malignancy is mesothelioma, because it is relatively rare and one of only a few neoplasms for which one specific inciting agent-asbestos-has been identified. Based on epidemiologic studies, approximately 15% of lung cancers in men and 5% of lung cancers in women are caused by occupational exposures. The International Agency for Research on Cancer has devised a rating system by which, based on animal and human data, they assign an agent, mixture, or exposure circumstance to one of five categories, ranging from group 1 (agent is carcinogenic to humans) to group 4 (agent is probably not carcinogenic to humans). Group 1 pulmonary carcinogens reviewed in this article include arsenic, asbestos, beryllium, bis (chloromethyl) ether, cadmium, chromium (IV), mustard gas, nickel, radon, and silica. The clinical presentation and pathology of lung cancers and mesothelioma caused by such exposures do not differ from those of cancers caused by other factors. The key to the recognition of a thoracic malignancy caused by workplace or environmental exposures is clinical suspicion and consideration of all causes for the disease present. Recognition of an exposure-related case of lung cancer or mesothelioma can aid in the identification of excess risk for a whole workforce or community and can lead to actions to reduce exposure, thus preventing future cases. In addition, such recognition allows the individuals struck by devastating illness to exercise their legal rights to compensation if so desired.}, } @article {pmid12064559, year = {2002}, author = {Kitamura, F and Araki, S and Suzuki, Y and Yokoyama, K and Tanigawa, T and Iwasaki, R}, title = {Assessment of the mutations of p53 suppressor gene and Ha- and Ki-ras oncogenes in malignant mesothelioma in relation to asbestos exposure: a study of 12 American patients.}, journal = {Industrial health}, volume = {40}, number = {2}, pages = {175-181}, doi = {10.2486/indhealth.40.175}, pmid = {12064559}, issn = {0019-8366}, mesh = {Aged ; Asbestos/*adverse effects ; Carcinogens/*adverse effects ; DNA Mutational Analysis ; DNA Primers ; Female ; Genes, p53/*genetics ; Genes, ras/*genetics ; Humans ; Male ; Mesothelioma/*chemically induced/*genetics ; Middle Aged ; *Occupational Exposure ; *Point Mutation ; Polymerase Chain Reaction ; Polymorphism, Single-Stranded Conformational ; }, abstract = {In our previous study, we found no genetic alteration in exons 1 and 2 of Ha- and Ki-ras oncogenes nor in exons 5 to 9 of the p53 suppressor gene in seven Japanese malignant mesothelioma patients exposed to asbestos. To examine further whether malignant mesothelioma due to asbestos has genetic alterations in the p53 suppressor gene and in Ha- and Ki-ras oncogenes, we analyzed point mutations of these genes in paraffin embedded operative open biopsied samples of the primary tumor of malignant mesothelioma in twelve American patients. The genetic analysis was conducted by the PCR-SSCP (polymerase chain reaction single-strand conformation polymorphism) method in all patients and by sequencing analysis of DNA bases in the two patients with suspected gene mutation. The analysis of the p53 suppressor gene showed an amino acid converting mutation of exon 7 in one patient and a polymorphism of exon 6 in another patient; the former patient was a heavy smoker with a biphasic cell type. No genetic alteration was found in exons 1 and 2 of Ha- and Ki-ras oncogenes in any of the patients. The results suggest that the effects of asbestos on the p53 suppressor gene and Ha- and Ki-ras oncogenes in malignant mesothelioma are negligible. Further studies are needed to examine whether the observed mutation of the p53 suppressor gene is due to the combined effects of asbestos and smoking or to other unknown factors.}, } @article {pmid12063622, year = {2002}, author = {Sohrab, S and Konietzko, N}, title = {[Diagnosis and staging of malignant pleural mesothelioma].}, journal = {Pneumologie (Stuttgart, Germany)}, volume = {56}, number = {6}, pages = {382-387}, doi = {10.1055/s-2002-32165}, pmid = {12063622}, issn = {0934-8387}, mesh = {Humans ; Mesothelioma/*diagnosis/pathology ; Neoplasm Staging ; Pleural Neoplasms/*diagnosis/pathology ; Prognosis ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive solid tumor with rising incidence and mortality. Due to a long latency period after asbestos exposure until tumor manifestation the peak of newly diagnosed MPM cases is to be expected for the year 2017 in Germany. One deciding factor for the poor prognosis with a median survival of 4 - 18 month is a late diagnosis at an advanced stage. Therefore, apart of improved stage related therapeutic options, early diagnostic procedures in suspected MPM play a key role. The diagnosis of MPM is made by the clinician as a synopsis of clinical, imaging and pathological findings. Computed tomography of the thorax and thoracoscopy with biopsy are the most important diagnostic procedures. Staging is recommended to be made as TNM description according to the International Mesothelioma Interest Group (IMIG) to allow a better comparability of various data in MPM.}, } @article {pmid12052665, year = {2002}, author = {Emri, S and Demir, A and Dogan, M and Akay, H and Bozkurt, B and Carbone, M and Baris, I}, title = {Lung diseases due to environmental exposures to erionite and asbestos in Turkey.}, journal = {Toxicology letters}, volume = {127}, number = {1-3}, pages = {251-257}, doi = {10.1016/s0378-4274(01)00507-0}, pmid = {12052665}, issn = {0378-4274}, mesh = {Asbestos/*adverse effects ; Carcinogens/*administration & dosage ; Environmental Exposure/*adverse effects ; Family Health ; HLA Antigens/metabolism ; Humans ; Lung Diseases/epidemiology/*etiology ; Mesothelioma/epidemiology/etiology/genetics ; Pleural Diseases/epidemiology/etiology ; Pleural Neoplasms/epidemiology/etiology/genetics ; Prevalence ; Prognosis ; Turkey/epidemiology ; Zeolites/*adverse effects ; }, abstract = {Asbestos deposits have been used locally by the rural inhabitants of Central and Southeastern Anatolia for domestic purposes for many years. Mineralogical analysis revealed that tremolite is the most prominent asbestos type found in the region. There is in addition another mineral fiber found particularly in three villages located in the Cappadocian region of Central Anatolia (zeolite villages). This is a non-asbestos mineral, which has been identified as the fibrous zeolite, erionite. This fiber is present in the volcanic tuffs, which are used as building stone. Hence, exposure to erionite fibers is always possible in the houses, annexes, and streets of the villages. It has been demonstrated that both asbestos and erionite cause a variety of benign and malignant chest diseases. Among the diseases, calcified pleural plaques (CPP) are the most frequently seen and may be used as an indicator of mineral fiber exposure. Asbestos and erionite exposure are the main causes of malignant mesotheliomas in Turkey. In zeolite villages malignant mesothelioma is responsible for more than 50% of the total deaths. A recent study showed that simian virus 40 is not a cofactor in the pathogenesis of environmental malignant mesothelioma in Turkey. An additional recent genetic-epidemiological study showed that there are some families, which are genetically predisposed to mesothelioma.}, } @article {pmid12046952, year = {2002}, author = {Yu, IJ and Choi, JK and Kang, SK and Chang, HK and Chung, YH and Han, JH and Song, KS and Lee, YM and Chung, HK}, title = {Potential source of asbestos in non-asbestos textile manufacturing company.}, journal = {Environment international}, volume = {28}, number = {1-2}, pages = {35-39}, doi = {10.1016/s0160-4120(02)00002-8}, pmid = {12046952}, issn = {0160-4120}, mesh = {Air Pollutants, Occupational/*adverse effects ; Asbestos, Crocidolite/*adverse effects ; Brain Neoplasms/secondary ; Humans ; Lung Neoplasms/*etiology/pathology ; Male ; Middle Aged ; Occupational Diseases/*etiology ; Occupational Exposure/adverse effects ; *Textile Industry ; Workers' Compensation ; Workplace ; }, abstract = {Recently, a worker with lung carcinoma and a metastatic brain tumor was diagnosed as having a work-related disease. He had been employed in a non-asbestos textile company for 25 years. Consequently, to identify and explore possible causative agents for lung cancer in a non-asbestos textile manufacturing company and establish a causal relationship between exposure and lung cancer, an epidemiological investigative study was conducted and the work processes the worker was engaged in were examined. Air samples were taken from the workplace and during the drilling processes, and a suspected causative material was analyzed. The study revealed that the subject had been employed in the non-asbestos textile manufacturing company for 25 years from 1973 and his responsibilities included repairing spinning machines. In particular, the subject was involved in drilling B-bushings that were used to protect against gear abrasion in the spinning machines. An analysis of the B-bushings using a transmission electron microscope equipped with an energy dispersive X-ray analyzer indicated that they contained crocidolite asbestos fibers. Air samples obtained when drilling the B-bushings clearly indicated that the subject had most likely been exposed to crocidolite fibers when installing the B-bushings in the spinning machines. The frequency and duration of the work suggested that there would be a sufficient degree of exposure to crocidolite fibers to cause lung cancer. Except for smoking and asbestos exposure, no other chemical exposure was suspected for developing lung cancer in the workplace. Smoking appeared to be more of a potentiating risk factor in conjunction with the asbestos exposure. Accordingly, this case may provide significant evidence in identifying the cause of the mesothelioma or lung carcinoma found among workers in non-asbestos textile manufacturing companies elsewhere.}, } @article {pmid12040923, year = {2002}, author = {Fischer, M and Günther, S and Müller, KM}, title = {Fibre-years, pulmonary asbestos burden and asbestosis.}, journal = {International journal of hygiene and environmental health}, volume = {205}, number = {3}, pages = {245-248}, doi = {10.1078/1438-4639-00149}, pmid = {12040923}, issn = {1438-4639}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Asbestosis/*complications/etiology ; Carcinogens/*adverse effects ; Humans ; Lung Neoplasms/*etiology/physiopathology ; Male ; Middle Aged ; *Occupational Exposure ; Pulmonary Fibrosis/etiology ; Time Factors ; }, abstract = {The relations between cumulative asbestos fibre doses at the work-places and asbestos burden of the lung evaluated by lung dust analyses have been tested on 3 different groups of patients of the German Mesothelioma Register: 1. total collective (n = 366), 2. collective without elevated asbestos burden of the lungs (n = 193), 3. collective with asbestoses/minimal asbestoses (n = 64). The relations between the above mentioned parameters are in general only weak. The limit value of > 25 fibre-years is found in 19.6% of persons without increased pulmonary asbestos burden. In spite of reaching or exceeding the cumulative doses of 25 fibre-years, 24% of the whole collective also show no elevated asbestos-concentrations in their lung tissues. By contrast, 42% of patients with asbestos-associated lung fibroses do not attain 25 fibre-years at their work-places. Considering our data it is doubtful that the postulated limit value of 25 fibre-years can be an adequate parameter for the evaluation of asbestos-associated lung fibroses.}, } @article {pmid12036093, year = {2002}, author = {Roggli, VL and Sharma, A and Butnor, KJ and Sporn, T and Vollmer, RT}, title = {Malignant mesothelioma and occupational exposure to asbestos: a clinicopathological correlation of 1445 cases.}, journal = {Ultrastructural pathology}, volume = {26}, number = {2}, pages = {55-65}, doi = {10.1080/01913120252959227}, pmid = {12036093}, issn = {0191-3123}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects/analysis/classification ; Body Burden ; Disease-Free Survival ; Female ; Humans ; Lung/metabolism ; Male ; Mesothelioma/*etiology/mortality/secondary ; Middle Aged ; Mineral Fibers/analysis/classification ; Occupational Exposure/*adverse effects/classification ; Peritoneal Neoplasms/*etiology/mortality/pathology ; Pleural Neoplasms/*etiology/mortality/pathology ; Survival Rate ; United States/epidemiology ; }, abstract = {Asbestos exposure is indisputably associated with development of mesothelioma. However, relatively few studies have evaluated the type of occupational exposure in correlation with asbestos fiber content and type. This study reports findings in 1445 cases of mesothelioma with known exposure history; 268 of these also had fiber burden analysis. The 1445 cases of mesothelioma were subclassified into 23 predominant occupational or exposure categories. Asbestos body counts per gram of wet lung tissue were determined by light microscopy. Asbestos fiber content and type were determined by scanning electron microscopy and energy dispersive x-ray analysis. Results were compared with a control group of 19 lung tissue samples. Ninety-four percent of the cases occurred among 19 exposure categories. Median asbestos body counts and levels of commercial and noncommercial amphibole fibers showed elevated levels for each of these 19 categories. Chrysotile fibers were detectable in 36 of 268 cases. All but 2 of these also had above-background levels of commercial amphiboles. When compared to commercial amphiboles, the median values for noncommercial amphibole fibers were higher in 4 of the 19 exposure groups. Most mesotheliomas in the United States fall into a limited number of exposure categories. Although a predominant occupation was ascertained for each of these cases, there was a substantial overlap in exposure types. All but 1 of the occupational categories analyzed had above-background levels of commercial amphiboles. Commercial amphiboles are responsible for most of the mesothelioma cases observed in the United States.}, } @article {pmid12024881, year = {2002}, author = {Waldron, HA}, title = {Fairchild and the "guilty" fibre.}, journal = {The Medico-legal journal}, volume = {70}, number = {Pt 2}, pages = {87-88}, doi = {10.1258/rsmmlj.70.2.87}, pmid = {12024881}, issn = {0025-8172}, mesh = {Asbestos/*adverse effects ; England ; Humans ; *Liability, Legal ; Mesothelioma/*etiology ; Occupational Exposure/*adverse effects/*legislation & jurisprudence ; }, } @article {pmid12005126, year = {2002}, author = {Rogers, A and Major, G}, title = {The quantitative risks of mesothelioma and lung cancer in relation to asbestos exposure: the Wittenoom data.}, journal = {The Annals of occupational hygiene}, volume = {46}, number = {1}, pages = {127-8; author reply 128-9}, doi = {10.1093/annhyg/mef002}, pmid = {12005126}, issn = {0003-4878}, mesh = {Asbestos, Crocidolite/*analysis ; Carcinogens/*analysis ; Humans ; Lung Neoplasms/*epidemiology/etiology ; Mesothelioma/*epidemiology/etiology ; Occupational Exposure/*analysis ; Risk Assessment/standards ; }, } @article {pmid12004841, year = {2002}, author = {Huncharek, M}, title = {Non-asbestos related diffuse malignant mesothelioma.}, journal = {Tumori}, volume = {88}, number = {1}, pages = {1-9}, pmid = {12004841}, issn = {0300-8916}, mesh = {Adolescent ; Adult ; Aged ; Child ; Diet/adverse effects ; Female ; Genetic Predisposition to Disease ; Humans ; Male ; Mesothelioma/*etiology/pathology ; Middle Aged ; Neoplasms, Radiation-Induced/etiology/pathology ; Pleural Neoplasms/*etiology/pathology ; Polyomavirus Infections/complications ; Simian virus 40/pathogenicity ; Tumor Virus Infections/complications ; }, abstract = {AIMS: The association between asbestos exposure and the development of malignant mesothelioma is well known. Nonetheless, a proportion of patients suffering from this disease do not appear to have documented exposure to asbestos fibers from any known source. Available information suggests that a true "background" incidence of this disease exits raising the possibility that other factors contribute to its etiology. This paper will review existing data related to non-asbestos related mesothelioma and suggest avenues for further research.

METHODS AND STUDY DESIGN: A comprehensive electronic MEDLARS search of the literature pertinent to non-asbestos related malignant mesothelioma was performed including the years 1996-2001. Hand searches were also carried out to supplement electronically derived information and literature pre-dating 1996. The resulting references were stratified into the following categories and reviewed; (1) radiation associated mesothelioma, (2) familial mesothelioma, (3) dietary factors, (4) childhood mesothelioma and (5) the role or SV40.

RESULT: Available information suggests that genetic factors may play a larger role in the etiology of this disease than currently appreciated. The interplay of genes and environment require further elucidation in the pathogenesis of mesothelioma. The role of diet is poorly understood with few studies directly addressing this issue. Whether other environmental or infectious agents are involved in mesothelioma development remains speculative.

CONCLUSION: The biology of mesothelioma is an enigma. Although this disease appears to occur in the absence of asbestos exposure, the genetic and biological differences between asbestos related and non-asbestos related tumors is unclear. Additional epidemiological and laboratory studies are needed to provide a better understanding of the relationship between environmental and non-environmental causes of mesothelioma.}, } @article {pmid12001992, year = {2002}, author = {Tweedale, G}, title = {Asbestos and its lethal legacy.}, journal = {Nature reviews. Cancer}, volume = {2}, number = {4}, pages = {311-315}, doi = {10.1038/nrc774}, pmid = {12001992}, issn = {1474-175X}, mesh = {Asbestos/*adverse effects ; Humans ; Industry ; Lung Neoplasms/*etiology/*mortality ; Mesothelioma/*etiology/*mortality ; Occupational Exposure ; Time Factors ; }, abstract = {Asbestos has become the leading cause of occupationally related cancer death, and the second most fatal manufactured carcinogen (after tobacco). In the public's mind, asbestos has been a hazard since the 1960s and 1970s. However, the knowledge that the material was a mortal health hazard dates back at least a century, and its carcinogenic properties have been appreciated for more than 50 years.}, } @article {pmid11996274, year = {2002}, author = {Gómez-Román, JJ and Mons-Lera, R and Olmedo, IS and Val-Bernal, JF}, title = {Flow cytometric analysis of a localized malignant mesothelioma.}, journal = {The Annals of thoracic surgery}, volume = {73}, number = {4}, pages = {1292-1294}, doi = {10.1016/s0003-4975(01)03261-1}, pmid = {11996274}, issn = {0003-4975}, mesh = {Aneuploidy ; DNA, Neoplasm/analysis ; Diagnosis, Differential ; Flow Cytometry ; Humans ; Immunohistochemistry ; Male ; Mesothelioma/chemistry/genetics/*pathology ; Middle Aged ; Pleural Neoplasms/chemistry/genetics/*pathology ; }, abstract = {Malignant mesothelioma usually presents as a diffuse neoplasm. We report a localized malignant mesothelioma in the parietal pleura of a patient who was not exposed to asbestos. A complete clinical, pathologic, and immunohistochemical description is provided. Flow cytometric analysis showed an aneuploid DNA content in neoplastic cells. The patient is alive and well 8 months after complete surgical resection. Localized malignant mesothelioma must be included in the differential diagnosis in chest wall-based neoplasms.}, } @article {pmid11995452, year = {2002}, author = {Schmidt, SC and Weidemann, H and Müller, KM and Krismann, M and Langrehr, JM and Neuhaus, P}, title = {Low malignant epithelioid peritoneal mesothelioma: successful treatment with surgical therapy alone.}, journal = {Hepato-gastroenterology}, volume = {49}, number = {44}, pages = {366-370}, pmid = {11995452}, issn = {0172-6390}, mesh = {Adult ; CA-125 Antigen/*blood ; Comorbidity ; Hernia, Inguinal/epidemiology/surgery ; Humans ; Male ; Mesothelioma/blood/epidemiology/*surgery ; Peritoneal Neoplasms/blood/epidemiology/*surgery ; }, abstract = {A 31-year-old man presented with malignant peritoneal mesothelioma. His past medical history was uneventful, specifically there was no personal or environmental asbestos exposure. The patient was treated by complete tumor resection including peritonectomy. Because of the histologic diagnosis of a low malignant, unusual highly differentiated epithelioid tumor with very low proliferative activity a postoperative chemotherapy was not administered. After a follow-up of 20 months, the patient is in excellent clinical condition and there is no evidence of disease by computed tomography. The present paper reports a case of this rare variant of malignant peritoneal mesothelioma.}, } @article {pmid11962950, year = {2000}, author = {Millar, B}, title = {Asbestos. 'A cruel and nasty disease'.}, journal = {Nursing times}, volume = {96}, number = {21}, pages = {32-33}, pmid = {11962950}, issn = {0954-7762}, mesh = {Asbestos/*adverse effects ; Europe/epidemiology ; Health Education/*organization & administration ; Humans ; Information Services/*organization & administration ; Male ; Mesothelioma/diagnosis/epidemiology/*etiology/therapy ; Middle Aged ; Needs Assessment ; Occupational Diseases/diagnosis/epidemiology/*etiology/therapy ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/diagnosis/epidemiology/*etiology/therapy ; Risk Factors ; }, } @article {pmid11943019, year = {2002}, author = {Serio, G and Scattone, A and Pennella, A and Giardina, C and Musti, M and Valente, T and Pollice, L}, title = {Malignant deciduoid mesothelioma of the pleura: report of two cases with long survival.}, journal = {Histopathology}, volume = {40}, number = {4}, pages = {348-352}, doi = {10.1046/j.1365-2559.2002.01373.x}, pmid = {11943019}, issn = {0309-0167}, mesh = {Adult ; Aged ; Antibodies/analysis ; Calbindin 2 ; Fatal Outcome ; Female ; Humans ; Keratins/analysis ; Ki-67 Antigen/analysis ; Male ; Mesothelioma/genetics/metabolism/*pathology ; Mitochondria/immunology ; Pleural Neoplasms/genetics/metabolism/*pathology ; S100 Calcium Binding Protein G/analysis ; Survival Analysis ; Time Factors ; }, abstract = {AIMS: To present two rare cases of malignant mesotheliomas with deciduoid features arising in the pleura, both with long survival.

METHODS AND RESULTS: These two cases of deciduoid mesotheliomas were observed in adult patients (one 73-year-old male and one 23-year-old female). Only the male had a history of occupational asbestos exposure, whereas the woman had a history of familial mesothelioma. A deciduoid morphology was predominant and focal areas with tubular-papillary features were noted. The tumour cells were positive for cytokeratins, HMBE-1, calretinin, EMA and mitochondrion antibodies. The follow-up data did not suggest a particularly poor prognosis; the mean survival observed was 23 months (17 and 39 months, respectively).

CONCLUSIONS: This deciduoid mesothelioma histological subtype does not appear to represent an unfavourable prognostic category.}, } @article {pmid11934952, year = {2002}, author = {Satin, KP and Bailey, WJ and Newton, KL and Ross, AY and Wong, O}, title = {Updated epidemiological study of workers at two California petroleum refineries, 1950-95.}, journal = {Occupational and environmental medicine}, volume = {59}, number = {4}, pages = {248-256}, pmid = {11934952}, issn = {1351-0711}, mesh = {Asbestos/adverse effects ; California/epidemiology ; Cause of Death ; Cohort Studies ; Extraction and Processing Industry/*statistics & numerical data ; Female ; Follow-Up Studies ; Humans ; Male ; Neoplasms/*mortality ; Occupational Diseases/*mortality ; Occupational Exposure/*statistics & numerical data ; Petroleum/adverse effects ; Risk Factors ; }, abstract = {OBJECTIVES: To further assess the potential role of occupational exposures on mortality, a second update of a cohort study of workers at two petroleum refineries in California was undertaken.

METHODS: Mortality analyses were based on standardised mortality ratios (SMRs) and 95% confidence intervals (95% CIs) using the general population of California as a reference. Additional analyses of lymphatic and haematopoietic cancer deaths and diseases related to asbestos were undertaken.

RESULTS: The update consisted of 18,512 employees, who contributed 456,425 person-years of observation between 1950 and 1995. Both overall mortality and total cancer mortality were significantly lower than expected, as were several site specific cancers and non-malignant diseases. In particular, no significant increases were reported for leukaemia cell types or non-Hodgkin's lymphoma. Mortality excess from multiple myeloma was marginally significant. The excess was confined to employees enrolled before 1949. Furthermore, there was no significant upward trend based on duration of employment, which argues against a causal interpretation relative to employment or exposures at the refineries. No increase was found for diseases related to asbestos: pulmonary fibrosis; lung cancer; or malignant mesothelioma. There was no significant increase in mortality from any other cancers or non-malignant diseases.

CONCLUSION: This second update provides additional reassurance that employment at these two refineries is not associated with increased risk of mortality.}, } @article {pmid11933817, year = {2002}, author = {Bolton, C and Richards, A and Ebden, P}, title = {Asbestos-related disease.}, journal = {Hospital medicine (London, England : 1998)}, volume = {63}, number = {3}, pages = {148-151}, doi = {10.12968/hosp.2002.63.3.2059}, pmid = {11933817}, issn = {1462-3935}, mesh = {Asbestos/*adverse effects ; Humans ; Lung Neoplasms/etiology ; Male ; Mesothelioma/etiology ; Occupational Diseases/*etiology ; Occupational Exposure/*adverse effects ; Pleural Diseases/etiology ; Prognosis ; Risk Factors ; Tomography, X-Ray Computed/methods ; Workers' Compensation ; }, abstract = {Until the 1980s, asbestos was widely used throughout the UK. The incidence of asbestos-related disease is still climbing because of the long delay in developing the disease from the initial exposure. The spectrum of diseases encompasses malignant mesothelioma, asbestosis, asbestos-related lung carcinoma and benign pleural disease, including pleural plaques.}, } @article {pmid11933738, year = {2002}, author = {Bard, M and Ruffié, P}, title = {[Malignant pleural mesothelioma. From diagnosis to prognosis].}, journal = {Presse medicale (Paris, France : 1983)}, volume = {31}, number = {9}, pages = {406-411}, pmid = {11933738}, issn = {0755-4982}, mesh = {Diagnosis, Differential ; Diagnostic Imaging ; Humans ; Mesothelioma/*diagnosis/*pathology/therapy ; Patient Selection ; Pleural Neoplasms/*diagnosis/*pathology/therapy ; Prognosis ; Thoracoscopy ; }, abstract = {EPIDEMIOLOGY: The incidence of malignant pleural mesothelioma has constantly increased over the past forty years. The recent measures of ban on the use of asbestos and the long latency of this tumor after exposure means that its peak incidence can be foreseen for the years 2010-2020.

DIAGNOSIS: Various health professionals are involved in the care of this tumor, which benefits equally from progresses in clinical and fundamental research. Some progress has been made in understanding its oncogenesis as well as its histopathologic analysis.

PROGNOSIS: Malignant pleural mesothelioma symptoms are rapidly invalidating and the patient's prognosis is bad at short-term. However, hope may come from the detection of early stages of the disease and from the individualization of good prognosis factors, permitting the selection of patients for whom some curative therapies are in course of evaluation.}, } @article {pmid11928673, year = {2001}, author = {Woźniak, H and Wiecek, E and Bielichowska-Cybula, G and Opalska, B}, title = {[Dust exposure and cancer risk associated with amphibolite mining and processing].}, journal = {Medycyna pracy}, volume = {52}, number = {6}, pages = {437-443}, pmid = {11928673}, issn = {0465-5893}, mesh = {Adult ; Asbestos, Amphibole/*adverse effects/analysis ; Carcinogens/*adverse effects/analysis ; Dust/*adverse effects/analysis ; Environmental Monitoring ; Humans ; Lung Neoplasms/chemically induced ; Maximum Allowable Concentration ; Mesothelioma/chemically induced ; *Mining ; Occupational Exposure/*adverse effects/analysis ; Poland ; Risk Assessment ; Time Factors ; }, abstract = {Mining and processing of amphibolite is associated with workers' exposure to dust containing asbestos minerals (actinolite, tremolite) and with the presence of respirable fibers, i.e. small particles above 5 microns long and below 3 microns in diameter (with length-to-diameter ratio higher than 3:1). Results of epidemiological and laboratory studies show that such dust may be responsible for the development of cancer in dust-exposed people. This work reports the measurement results of concentrations of total dust, respirable fibers and mineral composition of samples collected in plant mining and processing amphibolite rock. Based on the results, cumulated exposure was calculated for the 10-, 20- and 30-year exposure periods. The cumulated exposure was classified into two categories: 0.1-1.0 f/cm3 years and 1.0-10 f/cm3. x years. It has been found that mining and processing of amphibolite is associated with increased risk of death from mesothelioma--11.2 x 10(-5) (crushers--10 years of exposure) to 240.0 x 10(-5) (miners--30 years of exposure). The risk of excessive mortality from lung cancer was not high (below 1. x 10(-4)) for all workplaces and periods of exposure.}, } @article {pmid11923556, year = {2002}, author = {Baldi, A and Groeger, AM and Esposito, V and Cassandro, R and Tonini, G and Battista, T and Di Marino, MP and Vincenzi, B and Santini, M and Angelini, A and Rossiello, R and Baldi, F and Paggi, MG}, title = {Expression of p21 in SV40 large T antigen positive human pleural mesothelioma: relationship with survival.}, journal = {Thorax}, volume = {57}, number = {4}, pages = {353-356}, pmid = {11923556}, issn = {0040-6376}, mesh = {Antigens, Viral/immunology ; Cyclin-Dependent Kinase Inhibitor p21 ; Cyclins/*metabolism ; Humans ; Immunohistochemistry/methods ; Mesothelioma/*metabolism/mortality ; Pleural Neoplasms/*metabolism/mortality ; Simian virus 40/*immunology ; Survival Analysis ; T-Lymphocytes/immunology ; }, abstract = {BACKGROUND: Mesothelioma is the most commonly occurring primary pleural neoplasm. Several studies have documented an increase in the incidence of this malignancy during the last decades. Although the association between asbestos exposure and development of mesothelioma is generally accepted, the exact mechanism of carcinogenesis is unknown. Recently, Simian virus 40 large T antigen (SV40 Tag) expression has been detected in pleural mesothelioma. The ability of SV40 oncoproteins to inactivate p53 and retinoblastoma tumour suppressor proteins has been proposed as an important step in the pathogenesis of human mesothelioma.

METHODS: To obtain a better understanding of the molecular mechanisms of the pathogenesis of mesothelioma, the expression of the cell cycle inhibitor p21(WAF1/CIP1) (p21), a downstream target of p53, was evaluated immunohistochemically in a group of 29 mesothelioma specimens already characterised for the presence of SV40 Tag sequences.

RESULTS: Statistical analysis did not reveal any correlation between p21 expression and histopathological type of mesothelioma using the kappa(2) test (p=0.577). A significant positive relationship was found between p21 expression level and the patients' overall survival according to the Kaplan-Meier survival curves and using a log rank test (median difference in survival 7 months, 95% CI 4.8 to 9.9; p<0.001).

CONCLUSIONS: Determination of p21 expression bears a prognostic significance in patients affected with mesothelioma, further underlining the role of SV40 in the pathogenesis of malignant pleural mesothelioma.}, } @article {pmid11920963, year = {2002}, author = {Leigh, J and Davidson, P and Hendrie, L and Berry, D}, title = {Malignant mesothelioma in Australia, 1945-2000.}, journal = {American journal of industrial medicine}, volume = {41}, number = {3}, pages = {188-201}, doi = {10.1002/ajim.10047}, pmid = {11920963}, issn = {0271-3586}, mesh = {Adult ; Asbestos ; Australia/epidemiology ; Female ; Humans ; Incidence ; Male ; Mesothelioma/*epidemiology ; Mining/statistics & numerical data ; Occupational Diseases/*epidemiology ; Occupational Exposure/statistics & numerical data ; Pleural Neoplasms/*epidemiology ; Registries ; }, abstract = {BACKGROUND: Australia has maintained a total national malignant mesothelioma case register since 1980. There has been a marked increase in the incidence of mesothelioma in the last 20 years. Currently 450-600 cases are notified annually in a population of 20 million. While the history of the Wittenoom (Western Australia) crocidolite mine and its aftermath is well known, these cases comprise only 5% of the total. This study describes the incidence of mesothelioma in Australia from 1945 to 2000.

METHODS: Using register data, time trends in mesothelioma incidence were calculated. Analyses of incidence are reported by age, sex, anatomical site, and state of notification. Associations with occupational and environmental asbestos exposure histories are described. Lung fiber content measurements were made on a subset of cases.

RESULTS: Australia has had 6,329 cases of mesothelioma from 1 January 1945 to 31 December 2000. (A further 620 cases were notified in the period from 1 January 2001 to 31 October 2001.) Annual incidence rates for Australia per million population > or = 20 years (1997) were: male, 59.8; female, 10.9; total, 35.4. Incidence rates have been continually increasing and are the highest reported national rates in the world. While Western Australia has the highest rate (1997 total rate, 52.8), most cases arise from the two most populous eastern states, New South Wales and Victoria. In 88% (male 90%, female 61%) of cases, a history of asbestos exposure was obtained. Exposures occurred in a wide variety of occupational and environmental circumstances. In 80% of cases with no history of exposure, TEM lung asbestos fiber counts > 200,000 fibers > 2 microm length per gm dry lung were obtained, suggesting unrecognized exposure.

CONCLUSIONS: Australia's high incidence of mesothelioma is related to high past asbestos use, of all fiber types, in a wide variety of occupational and environmental settings. The number of cases in total is expected to be about 18,000 by 2020, with about 11,000 yet to appear.}, } @article {pmid11918175, year = {2002}, author = {Misdorp, W}, title = {Congenital tumours and tumour-like lesions in domestic animals. 1. Cattle. A review.}, journal = {The veterinary quarterly}, volume = {24}, number = {1}, pages = {1-11}, doi = {10.1080/01652176.2002.9695119}, pmid = {11918175}, issn = {0165-2176}, mesh = {Animals ; Animals, Newborn ; Cattle ; Cattle Diseases/*congenital/*pathology ; Environmental Exposure ; Genetic Predisposition to Disease ; Neoplasms/*congenital/pathology/*veterinary ; }, abstract = {The literature on congenital tumours and tumour-like lesions in calves was reviewed. Lesions were subdivided by their anatomical distribution and in addition also according to their histologic-pathogenetic nature. As a result of the latter method, four main groups were formed covering most of the lesions described so far: malignant lymphomas, mesotheliomas, hamartomas and embryonic tumours. Most lesions were of mesenchymal structure, carcinomas being extremely rare. Some findings may point to early genetic events, for instance twin calves both affected with malignant lymphoma and related calves with congenital facial neurofibromatosis. An external factor, asbestos, is suspected to play a role in the genesis of peritoneal mesotheliomatosis. The effects of congenital tumours on their hosts were often considerable: death by generalization (malignant lymphomas), ascites (mesotheliomas) or the growth of large abdominal tumours (nephroblastomas, mixed tumours). The latter two conditions often caused dystocia.}, } @article {pmid11881736, year = {2001}, author = {Erkiliç, S and Sari, I and Tunçözgür, B}, title = {Localized pleural malignant mesothelioma.}, journal = {Pathology international}, volume = {51}, number = {10}, pages = {812-815}, doi = {10.1046/j.1440-1827.2001.01279.x}, pmid = {11881736}, issn = {1320-5463}, mesh = {Aneuploidy ; Biomarkers, Tumor/analysis ; Female ; Flow Cytometry ; Humans ; Immunohistochemistry ; Keratins/analysis ; Mesothelioma/chemistry/*pathology/surgery ; Middle Aged ; Neoplasm Recurrence, Local/pathology/radiotherapy ; Pleural Neoplasms/chemistry/*pathology/surgery ; Radiography, Thoracic ; }, abstract = {Pleural malignant mesothelioma (PMM) is a rare tumor and it is commonly seen in the form of multiple nodules or a diffuse tumor. A localized tumor mass in the pleura is extremely rare. Only seven cases have been reported. In this report, we present an additional case of localized PMM and describe the immunohistochemical and flow cytometric findings. A 61-year-old woman, without a history of smoking or asbestos exposure, presented with a severe pain in her right shoulder and arm. Chest radiography showed a solitary mass in the right upper lung field. Computed tomography showed a 5 cm right upper lung mass. Magnetic resonance imaging showed that the mass extended to the wall of the thorax. The patient underwent surgery for total removal of the tumor. Pathology revealed a localized malignant mesothelioma. Immunohistochemical analysis showed that the tumor was strongly and diffusely positive for cytokeratins with high and low molecular weight, and focally positive for vimentin and epithelial membrane antigen (EMA), but it was negative for carcinoembryonic antigen, Factor VIII, alpha-fetoprotein and Leu-M1. Flow cytometry showed an aneuploid DNA content in the tumor. The final diagnosis was localized malignant mesothelioma (epithelial type). The patient showed signs of local recurrence 5 months after surgery, and radiotherapy was given.}, } @article {pmid11862475, year = {2002}, author = {Ehlers, EM and Kühnel, W and Wiedemann, GJ}, title = {Hyperthermia and mafosfamide in a human-derived malignant pleural mesothelioma cell line.}, journal = {Journal of cancer research and clinical oncology}, volume = {128}, number = {2}, pages = {65-72}, doi = {10.1007/s00432-001-0306-1}, pmid = {11862475}, issn = {0171-5216}, mesh = {Antineoplastic Agents/*pharmacokinetics/*pharmacology ; *Apoptosis ; Cell Cycle ; Combined Modality Therapy ; Cyclophosphamide/*analogs & derivatives/*pharmacokinetics/*pharmacology ; DNA Damage ; Flow Cytometry ; Humans ; *Hyperthermia, Induced ; Mesothelioma/*pathology ; Microscopy, Electron ; Pleural Neoplasms/*pathology ; Temperature ; Tumor Cells, Cultured ; }, abstract = {PURPOSE: Diffuse malignant pleural mesothelioma is the most common primary pleural malignancy. At the beginning of the last century, this tumor was of minor incidence. Meanwhile, the use of asbestos has led to and is still leading to a rise in pleural mesothelioma incidence. There is no standard therapy for this highly aggressive disease and the development of new therapeutic strategies is imperative.

METHODS: We, therefore, investigated the morphological and pharmakokinetic effects of a combined thermochemotherapy consisting of the administration of different dosages of mafosfamide with and without the application of a 1-h hyperthermia at 41.7 degrees C on the human biphasic malignant pleural mesothelioma cell line MSTO-211H. After therapy, cells were prepared for light and electron microscopy. BrdU-incorporation for the S-phase fraction, TUNEL-labeling for detection of apoptosis, and quantitative assessments using the MTT assay were performed.

RESULTS: Our results demonstrate that the combination of mafosfamide with hyperthermia leads to qualitatively and quantitatively enhanced cellular damage compared to monotherapy. During combined thermochemotherapy, cell damage and death is already induced at lower mafosfamide concentrations than without hyperthermia which suggests an additive effect from hyperthermia to the action of the alkylating drug mafosfamide. Cell death thereby mostly occurs as necrotic cell death rather than as apoptosis, although in a combined thermochemotherapy apoptosis is induced temperature-dependently, when comparing temperatures from 37 degrees C to 43 degrees C.

CONCLUSIONS: We suggest that the effect of substances such as ifosfamide and cyclophosfamide which are in clinical use, might be enhanced by the combination of local or regional hyperthermia in order to improve the therapeutical index of these substances in the treatment of pleural mesothelioma.}, } @article {pmid11857086, year = {2002}, author = {Foddis, R and De Rienzo, A and Broccoli, D and Bocchetta, M and Stekala, E and Rizzo, P and Tosolini, A and Grobelny, JV and Jhanwar, SC and Pass, HI and Testa, JR and Carbone, M}, title = {SV40 infection induces telomerase activity in human mesothelial cells.}, journal = {Oncogene}, volume = {21}, number = {9}, pages = {1434-1442}, doi = {10.1038/sj.onc.1205203}, pmid = {11857086}, issn = {0950-9232}, support = {CA-06927/CA/NCI NIH HHS/United States ; CA-45745/CA/NCI NIH HHS/United States ; }, mesh = {Blotting, Southern ; Cell Line, Transformed ; Cell Transformation, Neoplastic ; Cells, Cultured ; Enzyme Induction ; Epithelium/enzymology/pathology/virology ; Gene Deletion ; Humans ; Mesothelioma/*enzymology/*virology ; Simian virus 40/*physiology ; Telomerase/genetics/*metabolism ; Tumor Cells, Cultured ; }, abstract = {Mesotheliomas are malignant tumors of the pleural and peritoneal membranes which are often associated with asbestos exposure and with Simian virus 40 (SV40) infection. Telomerase activity is repressed in somatic cells and tissues but is activated in immortal and malignant cells. We evaluated telomerase activity in seven primary malignant mesothelioma biopsies and matched lung specimens and 20 mesothelioma cell lines and eight corresponding primary tumor cultures. All the tumor biopsies, and nearly all primary cell mesothelioma cultures and cell lines were telomerase positive. The findings in cell lines paralleled those observed in primary cultures in cases where paired samples were available. Next, we found that SV40, a DNA tumor virus present in approximately 50% of mesothelioma biopsies in the USA, induced telomerase activity in primary human mesothelial cells, but not in primary fibroblasts. Telomerase activity became detectable as early as 72 h following wild-type (strain 776) SV40 infection, and a clear DNA ladder was detectable 1 week after infection. The amount of telomerase activity increased during passage in cell culture and appeared to parallel increases in the cellular amounts of the SV40 large T-antigen. Thus, SV40 infection leads to telomerase activity before the infected mesothelial cells become transformed and immortalized. SV40 infection of human fibroblasts did not cause detectable telomerase activity. We also determined that the SV40 small t-antigen (tag) plays an important role in inducing telomerase activity because this activity was undetectable or minimal in mesothelial cells infected and/or transformed by SV40 tag mutants. Asbestos alone did not induce telomerase activity, and asbestos did not influence telomerase activity in mesothelial cells infected with SV40. Induction of telomerase activity by SV40 may be related to the very high rate of mesothelial cell immortalization that is characteristically associated with SV40 infection of mesothelial cells.}, } @article {pmid11852361, year = {2001}, author = {Chalabreysse, L and Guillaud, C and Tabib, A and Loire, R and Thivolet-Béjui, F}, title = {[Malignant mesothelioma with osteoblastic heterologous elements].}, journal = {Annales de pathologie}, volume = {21}, number = {5}, pages = {428-430}, pmid = {11852361}, issn = {0242-6498}, mesh = {Biopsy ; Calcinosis ; Diagnosis, Differential ; Humans ; Interferons/administration & dosage/therapeutic use ; Male ; Mesothelioma/*diagnosis/pathology ; Middle Aged ; Neoplasm Recurrence, Local ; Osteoblasts/*pathology ; Pleural Effusion ; Pleural Neoplasms/*diagnosis/pathology ; }, abstract = {A 59 year-old man with a history of asbestos exposure presented with a right pleural effusion and a diffuse pleural thickening with focal calcifications on chest X-ray. Cytological examination of pleural fluid indicated malignant mesothelioma. A biopsy specimen showed malignant mesothelioma surrounding a fragment of mature bone. The patient was treated with intrapleural interferon, but relapsed 3 years later. A fresh biopsy specimen showed round tumor cells surrounding osteoid substance. Only ten cases of this rare variant of malignant mesothelioma with osteoblastic heterologous elements have been reported in the literature. The most difficult differential diagnosis is primary pleural osteosarcoma.}, } @article {pmid11849743, year = {2002}, author = {Hirvonen, A and Tuimala, J and Ollikainen, T and Linnainmaa, K and Kinnula, V}, title = {Manganese superoxide dismutase genotypes and asbestos-associated pulmonary disorders.}, journal = {Cancer letters}, volume = {178}, number = {1}, pages = {71-74}, doi = {10.1016/s0304-3835(01)00819-9}, pmid = {11849743}, issn = {0304-3835}, mesh = {Asbestos/*adverse effects ; Asbestosis/*enzymology/etiology/genetics ; Cohort Studies ; DNA Primers/chemistry ; Female ; Genotype ; Humans ; Lymphocytes/physiology ; Male ; Mesothelioma/chemically induced/*enzymology/genetics ; Middle Aged ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/chemically induced/*enzymology/genetics ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Superoxide Dismutase/*genetics ; }, abstract = {Manganese superoxide dismutase (MnSOD) activity is highly elevated in the biopsies of human asbestos-associated malignant mesothelioma. We therefore examined if polymorphism in the mitochondrial targeting sequence of the MnSOD gene modified individual susceptibility to this malignancy or related asbestos-associated pulmonary disorders. The study population consisted of 124 male Finnish asbestos insulators who were all classified as having been exposed to high levels of asbestos; 63 of the workers had no pulmonary disorders and 61 either had malignant mesothelioma or the non-malignant pulmonary disorders asbestosis and/or pleural plaques. No significant associations were found between the MnSOD genotypes and these ill-health. This study therefore suggest no major modifying role for the MnSOD polymorphism in development of asbestos-associated pulmonary disorders.}, } @article {pmid11846639, year = {2002}, author = {Walker, AM and Maxim, LD and Utell, M}, title = {Risk analysis for mortality from respiratory tumors in a cohort of refractory ceramic fiber workers.}, journal = {Regulatory toxicology and pharmacology : RTP}, volume = {35}, number = {1}, pages = {95-104}, doi = {10.1006/rtph.2001.1513}, pmid = {11846639}, issn = {0273-2300}, mesh = {Adolescent ; Adult ; Aged ; *Asbestos/adverse effects ; Ceramics/*adverse effects ; Humans ; Longitudinal Studies ; Lung Neoplasms/epidemiology/*etiology/*mortality ; Mesothelioma/epidemiology/*etiology/*mortality ; Middle Aged ; Mineral Fibers/*adverse effects ; Occupational Diseases/epidemiology/*etiology/*mortality ; Risk Factors ; }, abstract = {Although workers in refractory ceramic fibers (RCF) manufacturing facilities have experienced no elevations in lung cancer or mesothelioma rates, the historical experience of asbestos together with animal studies of RCF have led to ongoing studies of the respiratory health of RCF workers. We have compared lung cancer and mesothelioma in the accumulated mortality experience of a cohort of male RCF production workers (Lemasters et al., 2001, submitted for publication) to that which would have been expected if RCF had a carcinogenic potency similar to that of various forms of asbestos. To accomplish this, we used risk models recently formalized by Hodgson and Darnton (2000, Ann. Occup. Hyg. 41, 13-36) for asbestos cohorts together with the RCF exposure measurements and historical reconstructions of Rice and colleagues (1997, Appl. Occup. Environ. Hyg. 12, 54-61). Deaths from lung cancer in the RCF cohort are statistically significantly below that which would be expected if RCF had the potency of either crocidolite or amosite. The mortality is also lower than would be expected if RCF had the potency of chrysotile, but the difference is not statistically significant. For mesothelioma, the anticipated numbers of deaths under hypotheses of asbestos-like potency are too small to be rejected by the zero cases seen in the RCF cohorts. The current epidemiologic studies do not rule out risk, but they clearly do rule out lung cancer risks like those of crocidolite or amosite. The residual uncertainty justifies ongoing workplace surveillance.}, } @article {pmid11845101, year = {2001}, author = {Desoubeaux, N and Bouvier, V and Gervais, R and Galateau-Salle, F and Thibon, P and Leplumey, T and Herbert, C and Lecherbonnier, Y and Daviet, JP and Letourneux, M}, title = {[Malignant mesothelioma in Basse-Normandie, a French population study. Descriptive analysis, prognostic factors and survival].}, journal = {Revue d'epidemiologie et de sante publique}, volume = {49}, number = {6}, pages = {523-529}, pmid = {11845101}, issn = {0398-7620}, mesh = {Age Factors ; Aged ; Asbestos/*adverse effects ; Cohort Studies ; Data Interpretation, Statistical ; Environmental Exposure/*adverse effects ; Female ; France/epidemiology ; Humans ; Male ; Mesothelioma/*epidemiology/etiology/mortality ; Middle Aged ; Occupational Exposure/*adverse effects ; Occupations ; Peritoneal Neoplasms/*epidemiology/etiology/mortality ; Pleural Neoplasms/*epidemiology/etiology/mortality ; Prognosis ; Sex Factors ; Survival Analysis ; Time Factors ; }, abstract = {BACKGROUND: Malignant mesothelioma is a pleural and/or peritoneal tumor closely related to asbestos exposure, and its incidence should continue to increase during the first two decades of the 21(rst)century. The main prognostic factors described for this tumor are older age, sex, tumor stage and histological type. The aim of this study was to assess the incidence of pleural and peritoneal malignant mesothelioma in the County of Basse-Normandie (France), as well as their epidemiological characteristics, and the prognostic factors related to survival duration.

METHODS: Cases were identified through repeated inquiries among all chest physicians and pathologists of the County of Basse-Normandie. A special care was taken in the validation of the diagnosis of each case. Incidence of mesothelioma was determined according to sex and age (5 years categories). Qualitative and quantitative variables were compared with the use of chi-square or Student's t tests respectively. Survival rate was calculated by Kaplan-Meier method, and prognostic factors were studied by means of Cox model.

RESULTS: Study population consisted in all 80 malignant mesothelioma cases diagnosed in Basse-Normandie between the 1(rst) of September 1995 and the 31(rst) of August 1999. Annual incidence rates of pleural mesothelioma were 1.1/100 000 in men and 0.23/100 000 in women; annual incidence rates for peritoneal mesothelioma were 0.21/100 000 in men and 0.13/100 000 in women. Asbestos exposure was present in 63 cases (78.8%). The study of geographic distribution of mesothelioma cases revealed the influence of the main asbestos industrial settings, as well as the numerous scattered cases related to other occupational exposure. Mean survival duration was 9 months for pleural mesothelioma and 5 months for peritoneal mesothelioma. After adjustment on age, death risk was higher in asbestos-exposed than in non asbestos-exposed cases.

CONCLUSION: This study confirms that malignant mesothelioma is closely related to asbestos exposure, but not only in main asbestos industrial settings. It suggests that asbestos exposure may take place among prognostic factors of this tumor.}, } @article {pmid11845099, year = {2001}, author = {Goldberg, M}, title = {[Asbestos: is there still a future for epidemiology?].}, journal = {Revue d'epidemiologie et de sante publique}, volume = {49}, number = {6}, pages = {505-511}, pmid = {11845099}, issn = {0398-7620}, mesh = {Adult ; Animals ; Asbestos/*adverse effects ; Asbestosis/*epidemiology ; Child ; Environmental Exposure ; Forecasting ; France/epidemiology ; Humans ; Incidence ; Lung Neoplasms/*etiology ; Male ; Mesothelioma/*etiology ; Middle Aged ; Occupational Exposure ; Pleural Neoplasms/*etiology ; Pulmonary Fibrosis/etiology ; Risk Factors ; }, } @article {pmid11836673, year = {2002}, author = {Nowak, AK and Lake, RA and Kindler, HL and Robinson, BW}, title = {New approaches for mesothelioma: biologics, vaccines, gene therapy, and other novel agents.}, journal = {Seminars in oncology}, volume = {29}, number = {1}, pages = {82-96}, doi = {10.1053/sonc.2002.30234}, pmid = {11836673}, issn = {0093-7754}, mesh = {Adjuvants, Immunologic/therapeutic use ; Angiogenesis Inhibitors/therapeutic use ; Animals ; Antigen Presentation ; Antigens, Neoplasm ; Antineoplastic Agents/therapeutic use ; Cancer Vaccines/therapeutic use ; Clinical Trials as Topic ; Cytokines/therapeutic use ; Endothelial Growth Factors ; ErbB Receptors ; Genetic Therapy ; Humans ; Immunologic Factors/therapeutic use ; Immunotherapy ; Interferons/therapeutic use ; Lymphokines ; Mesothelioma/genetics/immunology/metabolism/*therapy ; Platelet-Derived Growth Factor ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors ; }, abstract = {Although malignant mesothelioma is not a classically immunogenic cancer, there is abundant evidence for immune recognition. The relative ease of obtaining tumor tissue makes mesothelioma ideal for studying surrogate biomarkers such as lymphocytic infiltration or expression of transduced genes. There is evidence that malignant mesothelioma patients as well as asbestos-exposed persons without mesothelioma have impaired immune responsiveness. Substantial progress has been made in animal models using several biological and immunological techniques, but clinical application has been problematic. Systems studied have included lysis by interleukin-2 (IL-2)-activated lymphokine-activated killer (LAK) cells, tumor necrosis factor-alpha (TNF-alpha), a p16-expressing adenovirus vector, suicide gene therapy using the herpes simplex virus-tyrosine kinase (HSV-tk) followed by ganciclovir, and immunomodulatory gene therapy with IL-2, IL-4, interferon-gamma (IFN-gamma), IFN-alpha, TNF-alpha, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-6, and IL-1beta transfected into tumors. Vaccinia virus has been studied as a vector for cytokine gene transfer. Suicide gene therapy has been combined with a tumor vaccine. The University of Western Australia is initiating a pilot study of autologous vaccination in malignant mesothelioma. Novel agents under study include the angiogenesis inhibitors SU5416, bevacizumab, and thalidomide. ZD1839, an orally administered, highly selective inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase, is being tested in a phase II trial. Since platelet-derived growth factor (PDGF) is thought to be an autocrine growth factor for mesothelioma STI-571 (Gleevec; Novartis, Basel, Switzerland), a highly selective inhibitor of the PDGF receptor tyrosine kinase, is being tested in a phase II trial. The development of more active cytotoxic combinations in this disease should facilitate further studies of chemoimmunotherapy. It seems likely that no single treatment modality will be effective by itself.}, } @article {pmid11836666, year = {2002}, author = {Marom, EM and Erasmus, JJ and Pass, HI and Patz, EF}, title = {The role of imaging in malignant pleural mesothelioma.}, journal = {Seminars in oncology}, volume = {29}, number = {1}, pages = {26-35}, doi = {10.1053/sonc.2002.30228}, pmid = {11836666}, issn = {0093-7754}, mesh = {Biopsy, Needle ; Humans ; Magnetic Resonance Imaging ; Mesothelioma/*diagnosis ; Neoplasm Staging ; Pleural Neoplasms/*diagnosis ; Tomography, Emission-Computed ; Tomography, X-Ray Computed ; }, abstract = {Imaging plays an essential role in the diagnosis, staging, and follow-up of patients with malignant pleural mesothelioma (MPM). The diagnosis is often suggested by a unilateral pleural mass with a moderate to large pleural effusion seen on chest radiographs, but computerized tomography (CT) is the most frequently used technique for evaluation of the lungs in patients with MPM. CT not only suggests pulmonary metastases typically manifested as nodules or masses, but also can demonstrate underlying lung disease often caused by prior asbestos exposure. Magnetic resonance (MR) imaging may be helpful in selected patients with potentially resectable disease to further examine the local extent of tumor. Imaging with positron emission tomography (PET) using the radionuclide imaging agent (18)F fluoro-deoxyglucose (FDG) takes advantage of a basic property of tumor cells, increased glucose metabolism to identify malignant lesions. PET provides not only anatomic information, especially regarding mediastinal node metastasis, but also biochemical information about the lesion. These imaging modalities help triage patients to the most appropriate diagnostic and treatment options. Following patients after therapy usually relies on chest radiographs, although CT can more accurately describe response to therapy. This review will focus on radiologic evaluation in diagnosing, staging, and follow-up patients with MPM.}, } @article {pmid11836665, year = {2002}, author = {Britton, M}, title = {The epidemiology of mesothelioma.}, journal = {Seminars in oncology}, volume = {29}, number = {1}, pages = {18-25}, doi = {10.1053/sonc.2002.30237}, pmid = {11836665}, issn = {0093-7754}, mesh = {Asbestos/*adverse effects ; Asbestos, Amphibole/adverse effects ; Asbestos, Crocidolite/adverse effects ; Case-Control Studies ; Cohort Studies ; Global Health ; Humans ; Lung Neoplasms/epidemiology/etiology ; Mesothelioma/*epidemiology/etiology ; Occupational Diseases/*epidemiology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*epidemiology/etiology ; }, abstract = {It has been more than 40 years since occupational crocidolite exposure in South African miners was found to be associated with development of malignant mesothelial tumors 30 to 40 years later. Similar cases were not seen in the amosite and chrysotile miners. Since then, epidemiological and toxicological knowledge have increased enormously, but mortality continues to rise steeply (5% to 10% per year) in most industrialized countries. Even with widespread asbestos abatement efforts, this increase is likely to continue in Western Europe and the United State well into the next century, at least until 2020. Unregulated use of asbestos in less industrialized countries may cause the epidemic to continue throughout the next century in those regions. Asbestos abatement seems to be successful as evidenced by a decline in the proportion of patients with peritoneal tumors, which are the most common malignancies in heavily exposed individuals. Whereas in the 1960s peritoneal tumors comprised up to 30% of the total, in recent years the proportion has fallen to about 10%, This changing ratio could also be due to the steady increase in pleural tumors. The difficulty in formulating the connection as to the etiology of mesothelioma resulted from an unforeseeable difference in the carcinogenicity of various asbestos and mineral fiber types and was compounded by the very long latency of the disease. Unfortunately, the use of a single term, "asbestos," to describe at least five fibrous silicate minerals, each with unique physical, chemical, and biological properties and not infrequently and naturally admixed, severely hampered scientific investigation into the occupational health risks. The field became confused and filled with debate. At the heart of the fiber type controversy lies a fundamentally differing view of the importance of biopersistence of various asbestos fibers in carcinogenesis. This review will deal with the epidemiology of mesothelioma with particular attention to the studies that elucidate the impact of various asbestos fiber types on the etiology of the disease.}, } @article {pmid11836664, year = {2002}, author = {Carbone, M and Kratzke, RA and Testa, JR}, title = {The pathogenesis of mesothelioma.}, journal = {Seminars in oncology}, volume = {29}, number = {1}, pages = {2-17}, doi = {10.1053/sonc.2002.30227}, pmid = {11836664}, issn = {0093-7754}, support = {CA 77220/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Asbestos/adverse effects ; Disease Models, Animal ; Genes, Tumor Suppressor ; Humans ; Mesothelioma/epidemiology/*etiology/genetics/virology ; Neoplasms, Radiation-Induced ; Neoplasms, Second Primary ; Occupational Exposure/adverse effects ; Pleural Neoplasms/epidemiology/*etiology/genetics/virology ; Polyomavirus Infections ; Simian virus 40 ; Tumor Virus Infections ; Turkey/epidemiology ; Zeolites/adverse effects ; }, abstract = {About 80% of malignant mesotheliomas (MM) in the Western World develop in individuals with higher than background exposure to asbestos. Only a fraction of those exposed to asbestos develop mesothelioma, indicating that additional factors play a role. Simian virus 40 (SV40), a DNA tumor virus that preferentially causes mesothelioma in hamsters, has been detected in several human mesotheliomas. The expression of the SV40 large tumor antigen in mesothelioma cells, and not in nearby stromal cells, and the capacity of antisense T-antigen treatment to arrest mesothelioma cell growth in vitro suggest that SV40 contributes to tumor development. The capacity of T-antigen to bind and inhibit cellular p53 and retinoblastoma (Rb)-family proteins in mesothelioma, together with the very high susceptibility of human mesothelial cells to SV40-mediated transformation in vitro, supports a causative role of SV40 in the pathogenesis of mesothelioma. Asbestos appears to increase SV40-mediated transformation of human mesothelial cells in vitro, suggesting that asbestos and SV40 may be cocarcinogens. p53 mutations are rarely found in mesothelioma; p16, p14ARF, and NF2 mutations/losses are frequent. Recent studies revealed the existence of a genetic factor that predisposes affected individuals to mesothelioma in the villages of Karain and Tuzkoy, in Anatolia, Turkey. Erionite, a type of zeolite, may be a cofactor in these same villages, where 50% of deaths are caused by mesothelioma. Mesothelioma appears to have a complex etiology in which environmental carcinogens (asbestos and erionite), ionizing radiation, viruses, and genetic factors act alone or in concert to cause malignancy.}, } @article {pmid11828058, year = {2002}, author = {Rudd, R and Moore-Gillon, J and Muers, M}, title = {Mesothelioma.}, journal = {Thorax}, volume = {57}, number = {2}, pages = {187}, doi = {10.1136/thorax.57.2.187}, pmid = {11828058}, issn = {0040-6376}, mesh = {Asbestos/*adverse effects ; *Expert Testimony ; Humans ; Liability, Legal ; Mesothelioma/*etiology ; Mineral Fibers ; Occupational Exposure/adverse effects ; United Kingdom ; Workers' Compensation/legislation & jurisprudence ; }, } @article {pmid11828056, year = {2002}, author = {Robinson, M and Wiggins, J}, title = {Statement on malignant mesothelioma in the UK.}, journal = {Thorax}, volume = {57}, number = {2}, pages = {187}, doi = {10.1136/thorax.57.2.187-a}, pmid = {11828056}, issn = {0040-6376}, mesh = {*Asbestos ; Humans ; Mesothelioma/*etiology ; Occupational Exposure/adverse effects ; Self-Help Groups ; United Kingdom ; }, } @article {pmid11828054, year = {2002}, author = {Seaton, A}, title = {One fibre or many; what causes mesothelioma?.}, journal = {Thorax}, volume = {57}, number = {2}, pages = {186-187}, doi = {10.1136/thorax.57.2.186-b}, pmid = {11828054}, issn = {0040-6376}, mesh = {Asbestos/*adverse effects ; Cell Transformation, Neoplastic ; Humans ; Liability, Legal ; Male ; Mesothelioma/*etiology ; Middle Aged ; Mineral Fibers ; Occupational Exposure/adverse effects ; United Kingdom ; Workers' Compensation/*legislation & jurisprudence ; }, } @article {pmid11813251, year = {2002}, author = {De Rienzo, A and Tor, M and Sterman, DH and Aksoy, F and Albelda, SM and Testa, JR}, title = {Detection of SV40 DNA sequences in malignant mesothelioma specimens from the United States, but not from Turkey.}, journal = {Journal of cellular biochemistry}, volume = {84}, number = {3}, pages = {455-459}, pmid = {11813251}, issn = {0730-2312}, support = {CA-06927/CA/NCI NIH HHS/United States ; CA-45745/CA/NCI NIH HHS/United States ; }, mesh = {Blotting, Southern ; DNA, Viral/analysis ; Humans ; Mesothelioma/*virology ; Polymerase Chain Reaction ; Simian virus 40/genetics/*isolation & purification ; Turkey ; United States ; }, abstract = {The incidence of malignant mesothelioma (MM) shows a strong epidemiological association with exposure to asbestos fibers. Recently, simian virus 40 (SV40) DNA sequences have been reported in MM tumor specimens from the United States and several European countries, and the SV40 tumor virus has been implicated as a potential co-factor in the etiology of this disease. However, several large studies from the US, Finland, and Turkey did not detect SV40 sequences in MM samples. To address this discrepancy, MM specimens from Turkey and the US were analyzed in the same laboratory under identical conditions to detect the presence of SV40 DNA. We detected SV40 sequences in 4 of 11 specimens from the United States, but in none of the 9 Turkish samples examined. These findings suggest that geographical differences exist with regard to the involvement of SV40 in human tumors.}, } @article {pmid11811924, year = {2002}, author = {Manning, CB and Vallyathan, V and Mossman, BT}, title = {Diseases caused by asbestos: mechanisms of injury and disease development.}, journal = {International immunopharmacology}, volume = {2}, number = {2-3}, pages = {191-200}, doi = {10.1016/s1567-5769(01)00172-2}, pmid = {11811924}, issn = {1567-5769}, support = {ES/HL09213/ES/NIEHS NIH HHS/United States ; P01HL67004/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Asbestos/*adverse effects ; Asbestosis/*etiology/genetics/immunology/*pathology ; Carcinogens/*adverse effects ; Carcinoma, Bronchogenic/etiology/genetics/immunology/pathology ; Humans ; Mesothelioma/etiology/genetics/immunology/pathology ; }, abstract = {Asbestos is a ubiquitous, naturally occurring fiber that has been linked to the development of malignant and fibrotic diseases of the lung and pleura. These diseases may be initiated by injury to epithelial cells and mesothelial cells by asbestos fibers through the formation of reactive oxygen intermediates. Elaboration of oxidants are also a consequence of inflammation, a hallmark of exposure to asbestos after inhalation or injection of asbestos fibers into animals. The type, size, and durability of asbestos fibers may be important in toxicity and pathogenicity of asbestos types. This review discusses the pathways of oxidant generation by asbestos fibers, cell-cell interaction that may initiate and perpetuate inflammation, cytokine release and proliferative responses to asbestos, and cell signaling pathways implicated in these events.}, } @article {pmid11811303, year = {2001}, author = {Trosić, I}, title = {Fate of the miraculous mineral--ban asbestos worldwide campaign.}, journal = {Collegium antropologicum}, volume = {25}, number = {2}, pages = {713-718}, pmid = {11811303}, issn = {0350-6134}, mesh = {Asbestos/*adverse effects ; Carcinogens/*adverse effects ; *Environmental Exposure ; *Global Health ; Hazardous Substances ; Humans ; Industry ; Mineral Fibers/*adverse effects ; Public Policy ; }, abstract = {Asbestos is a generic term used to describe natural mineral fibers found in the ground in many regions of the world. This cheap material with special chemical and physical properties that make it virtually indestructible was widely used in the 20th century. Within twenty years of the first industrial production, the public health hazards associated with asbestos started to come to light. Asbestos has become one of the most worrying industrial pollutants, since it poses a health hazard of asbestosis, lung cancer, mesotheliomas, and benign changes in the pleura. In spite of the WHO recommendations, environmental health criteria and their revision, asbestos is still around.}, } @article {pmid11797859, year = {2001}, author = {Stallard, E}, title = {Product liability forecasting for asbestos-related personal injury claims: a multidisciplinary approach.}, journal = {Annals of the New York Academy of Sciences}, volume = {954}, number = {}, pages = {223-244}, doi = {10.1111/j.1749-6632.2001.tb02754.x}, pmid = {11797859}, issn = {0077-8923}, mesh = {Asbestos/*adverse effects ; Asbestosis/*epidemiology/etiology ; Female ; Forecasting/*methods ; Humans ; *Jurisprudence ; Lung Neoplasms/*epidemiology/etiology ; Male ; Mesothelioma/*epidemiology/etiology ; Occupational Diseases/*epidemiology/etiology ; Risk Factors ; SEER Program ; }, abstract = {This paper focuses on three aspects of forecasting models for asbestos-related disease/injuries relating to the Manville asbestos case: (1) The structure of forecasting models for asbestos-related personal injuries. (2) The epidemiologic evidence supporting the selected model structure and the constraints on the modeling assumptions imposed by that evidence. (3) The range of uncertainty associated with projections based on these forecasting models and issues relating to decision making under uncertainty.}, } @article {pmid11796462, year = {2002}, author = {Galani, V and Constantopoulos, S and Manda-Stachouli, C and Frangou-Lazaridis, M and Mavridis, A and Vassiliou, M and Dalavanga, Y}, title = {Additional proteins in BAL fluid of Metsovites environmentally exposed to asbestos: more evidence of "protection" against neoplasia?.}, journal = {Chest}, volume = {121}, number = {1}, pages = {273-278}, doi = {10.1378/chest.121.1.273}, pmid = {11796462}, issn = {0012-3692}, mesh = {Adult ; Aged ; Asbestos, Amphibole/*adverse effects ; Asbestosis/*diagnosis/etiology/immunology ; Bronchoalveolar Lavage Fluid/*chemistry/immunology ; Calcinosis/*diagnosis/etiology/immunology ; Complement C4/analysis ; Environmental Exposure/*adverse effects ; Female ; Greece ; Humans ; Immunoglobulin A/analysis ; Immunoglobulin G/analysis ; Immunoglobulin Heavy Chains/analysis ; Interleukin-6/analysis ; Lymphocytosis/diagnosis/etiology/immunology ; Male ; Mesothelioma/*diagnosis/etiology/immunology ; Middle Aged ; Pleural Diseases/*diagnosis/etiology/immunology ; Pleural Neoplasms/*diagnosis/etiology/immunology ; Prognosis ; Proteins/*analysis ; }, abstract = {INTRODUCTION: Inhabitants of Metsovo in northwest Greece have been exposed to asbestos from use of a tremolite-containing whitewash ("luto" soil). As a result, they have increased incidence of malignant pleural mesothelioma and pleural calcifications (PCs). However, subjects with calcifications have a much lower incidence of mesothelioma than those without. A previous study of the two groups with BAL revealed higher proportional lymphocytosis among subjects with calcifications. We suggested that BAL lymphocytosis may be somehow correlated with "protection" against neoplasia.

METHODS: The present report is a study of the liquid phase of BAL in the two groups. BAL specimens of 43 Metsovites (13 subjects with PCs and 30 subjects without PCs) and two control groups were examined. We measured total protein, albumin, IgG, IgA, and interleukin-6. Proteins were analyzed with sodium dodecyl sulfate-polyacrylamide gel electrophoresis and two-dimensional electrophoresis and further characterized using an appropriate computer program.

RESULTS: The most interesting finding was the presence of two additional protein spots corresponding to the electrophoretic site of Ig heavy chain and C(4) component of complement. The two proteins were present in all Metsovites with PCs but in none without PCs and also in none of the control groups.

CONCLUSION: This study further separates two groups of Metsovites with different reaction to asbestos, possibly as a result of different activation of alveolar macrophages. This difference leads the first group to the formation of PCs, BAL fluid lymphocytosis, and relative "protection" against malignancy, and the second group to no calcifications, no lymphocytosis, but also no protection against malignancy.}, } @article {pmid11785373, year = {2001}, author = {Neumeister, W and Gillissen, A and Rasche, K and Müller, KM and Schultze-Werninghaus, G}, title = {[Pleural mesothelioma. I: History, epidemiology, clinical aspects (symptoms, diagnosis)].}, journal = {Medizinische Klinik (Munich, Germany : 1983)}, volume = {96}, number = {12}, pages = {722-729}, doi = {10.1007/pl00002168}, pmid = {11785373}, issn = {0723-5003}, mesh = {Asbestos/adverse effects ; Cause of Death/trends ; Cross-Sectional Studies ; Diagnosis, Differential ; Forecasting ; Germany/epidemiology ; Humans ; Incidence ; Mesothelioma/*diagnosis/etiology/mortality ; Pleural Neoplasms/*diagnosis/etiology/mortality ; }, abstract = {EPIDEMIOLOGY: Although production and processing of asbestos have been prohibited for years, the incidence of mesothelioma of the pleura will rise in Western Europe. The incidence of mesothelioma will peak between the years 2010 and 2020. It will cause an estimated 250,000 deaths within the next 35 years.

PATHOGENESIS: The fact that exposure to asbestos fibers may result in mesothelioma was first described in 1960. The risk of developing mesothelioma depends mainly on the type of asbestos fibers and the way asbestos is manufactured. Environmental eronite fibers in Central Turkey are the cause of endemic mesothelioma. The pathogenetic role of infection with simian virus 40 is still not determined. Thoracic radiation is of minor importance in the etiology of pleural mesothelioma.

DIAGNOSIS: Between first symptoms of disease and diagnosis of mesothelioma often more than 6 months pass as clinical symptoms are rarely typical. Detection of early stages by invasive procedures and imaging is often very difficult. Histopathological distinction between adenocarcinoma and mesothelioma requires experienced pathologists. This implies that management of mesothelioma should only be performed in multidisciplinary cooperation in specialized centers.}, } @article {pmid11782365, year = {2002}, author = {Unfried, K and Schürkes, C and Abel, J}, title = {Distinct spectrum of mutations induced by crocidolite asbestos: clue for 8-hydroxydeoxyguanosine-dependent mutagenesis in vivo.}, journal = {Cancer research}, volume = {62}, number = {1}, pages = {99-104}, pmid = {11782365}, issn = {0008-5472}, mesh = {8-Hydroxy-2'-Deoxyguanosine ; Animals ; Animals, Genetically Modified ; Asbestos, Crocidolite/*toxicity ; Chromatography, High Pressure Liquid ; DNA/drug effects/genetics/metabolism ; *DNA Damage ; Deoxyguanosine/*analogs & derivatives/*genetics/metabolism ; Electrochemistry ; Female ; Mutagenicity Tests ; Omentum/drug effects/metabolism/physiology ; Rats ; Rats, Inbred F344 ; }, abstract = {DNA damage due to reactive oxygen or nitrogen species is proposed to be involved in the molecular mechanism of asbestos-induced carcinogenicity. However, indications for this hypothesis came mainly from in vitro assays using cultured cells or cell-free systems. In the present study, the mutagenicity of crocidolite fibers and the underlying molecular mechanisms were investigated in vivo. Mutation frequencies were determined in DNA of omenta, a relevant target tissue for mesothelioma carcinogenesis, using lacI transgenic rats. The mutagenic effect of 2 and 5 mg of crocidolite asbestos was demonstrated, with a maximal relative increase in mutation frequency of 3.4 compared with the control group. The molecular analysis of the mutations revealed striking differences according to mutation types between asbestos-induced mutations and spontaneous mutations. Therefore, a specific molecular mechanism induced by crocidolite that differs from that induced by the generation of spontaneous mutations can be proposed. G to T transversions, which are known to be induced by the premutagenic DNA adduct 8-hydroxydeoxyguanosine (8-OHdG), were the most prominent mutation type (29%) within crocidolite-induced mutations. In additional experiments, 8-OHdG in DNA of omenta from rats treated with 1 or 2 mg of crocidolite asbestos was determined. Levels of 8-OHdG in animals treated with crocidolite were significantly increased compared with negative controls. These data give strong evidence for the involvement of reactive oxygen or nitrogen species in crocidolite-induced mutagenesis in vivo.}, } @article {pmid11758993, year = {2001}, author = {Ramanathan, AL and Subramanian, V}, title = {Present status of asbestos mining and related health problems in India--a survey.}, journal = {Industrial health}, volume = {39}, number = {4}, pages = {309-315}, doi = {10.2486/indhealth.39.309}, pmid = {11758993}, issn = {0019-8366}, mesh = {Asbestos, Amphibole/*adverse effects ; Asbestos, Serpentine/*adverse effects ; Asbestosis/*epidemiology/physiopathology ; Environmental Exposure/adverse effects ; Female ; Humans ; India/epidemiology ; Male ; *Mining ; Occupational Exposure/*adverse effects/standards ; Respiratory Function Tests ; Sex Factors ; Smoking/adverse effects ; Time Factors ; }, abstract = {At present in India more than thirty mines are in operation. It produces 2800 tones of asbestos per month (mainly chrysotile and tremolite) and in recent years substantial quantity (-70%) is imported from Canada. The quality of asbestos produced in India is very poor. The mining and milling and other related processes expose the people to cancer and related diseases. Women are more affected by their exposure in processing unit compared to male who are generally working in mines. Direct and indirect employment in asbestos related industry and mine is around 100,000 workers. Latency period (length of the time between exposure and the onset of diseases) in India is estimated to be 20-37 yr. The causes for lung and breathing problem are mainly due to obsolete technology and direct contact with the asbestos products without proper precaution, because in India asbestos are sold without statutory warning. This paper reviews health effects (such as fibrosis, sequelae, bronchogenic cancer, and malignant mesothelioma) on the Indian mine workers caused due to asbestos mining related activities with respect to their present day condition.}, } @article {pmid11757221, year = {2001}, author = {Nalepa, P and Zieliński, M}, title = {[Two cases of malignant mesothelioma of the pleura within one family].}, journal = {Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego}, volume = {11}, number = {62}, pages = {165-168}, pmid = {11757221}, issn = {1426-9686}, mesh = {Adult ; Female ; Humans ; Male ; Mesothelioma/*genetics/*pathology/surgery ; Pleural Neoplasms/*genetics/*pathology/surgery ; }, abstract = {The two patients (brothers) had in their early childhood contact with asbestos (asbestos blanket). Because of various degree of disease advancement, various methods of treatment were used. One brother was treated with radical surgery followed by radiotherapy; the other brother with more advanced disease underwent palliative treatment using chemotherapy. The patient who underwent surgery has been living for three years now free of tumour relapse, where's in the patient treated with chemotherapy, after partial remission of the disease, a relapse of tumor was observed. Currently, he undergoes symptomatic treatment. The cases above have been presented because the familial occurrence of this neoplasm is extremely rare and to show the possibility of radical surgical treatment of this type of neoplasm which has poor prognosis.}, } @article {pmid11750708, year = {2002}, author = {Tiitola, M and Kivisaari, L and Huuskonen, MS and Mattson, K and Koskinen, H and Lehtola, H and Zitting, A and Vehmas, T}, title = {Computed tomography screening for lung cancer in asbestos-exposed workers.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {35}, number = {1}, pages = {17-22}, doi = {10.1016/s0169-5002(01)00294-x}, pmid = {11750708}, issn = {0169-5002}, mesh = {Adenocarcinoma/*diagnostic imaging/etiology/surgery ; Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Asbestosis/*diagnostic imaging/etiology ; Carcinogens/*adverse effects ; False Negative Reactions ; False Positive Reactions ; Female ; Humans ; Lung Neoplasms/*diagnostic imaging/epidemiology/etiology/surgery ; Male ; Mass Screening/methods ; Middle Aged ; Occupational Exposure/*adverse effects ; Pleura/*diagnostic imaging ; Prevalence ; Sensitivity and Specificity ; Tomography, X-Ray Computed/methods ; }, abstract = {We conducted a computed tomography (CT) screening for lung cancer in a high-risk population. Six hundred and two workers (38-81 years, 97% smokers) with asbestos-related occupational disease were screened using spiral CT and chest radiography. The national cancer registry was checked for possible false negative cases. The screening detected 111 patients with non-calcified nodules >0.5 cm in diameter and 66 of them were referred for further hospital examination. We found five lung cancers (106 false positive cases) with a histological spectrum similar to the national, natural occurrence of the disease (two adeno, one squamous cell, one anaplastic and one metastatic carcinoma) and one peritoneal mesothelioma. Three cases were potentially operable (stage I-II). Unfortunately there was one false negative fine-needle aspiration biopsy (FNAB) with misinterpretation of the follow-up CT scan and another patient who refused further investigations after an inadequate FNAB. In the end only one patient with adenocarcinoma underwent surgery. After 3 years of follow-up two new lung cancers were reported to the cancer registry with no evidence of tumour in the retrospective analysis of the screening CT scan. The sensitivity of CT screening was 100%. CT was capable of detecting early lung cancer in asbestos-exposed patients with a lot of confusing pulmonary and pleural pathology. Due to the high number of positive findings attention should be paid to patient compliance and the follow-up protocols and patient selection in future screening programmes.}, } @article {pmid11746245, year = {2001}, author = {Kravchenko, IV and Furalyov, VA and Vasylieva, LA and Pylev, LN}, title = {Inhibition of asbestos-induced transformation of rat pleural mesothelial cells in co-culture with rat macrophages.}, journal = {Teratogenesis, carcinogenesis, and mutagenesis}, volume = {21}, number = {5}, pages = {315-323}, doi = {10.1002/tcm.1019}, pmid = {11746245}, issn = {0270-3211}, mesh = {Animals ; Asbestos/*toxicity ; Cell Transformation, Neoplastic/*chemically induced ; Coculture Techniques ; Macrophages/*physiology ; Mesothelioma/*prevention & control ; Pleural Neoplasms/*prevention & control ; Rats ; }, abstract = {The aim of this work was to investigate the influence of macrophages on the process of rat pleural mesothelium cells (RPMC) transformation in vitro. For this purpose prolonged many-passage co-cultivation of rat pleural mesothelial cells and rat peritoneal macrophages was performed both in the presence (to study macrophage influence on asbestos-induced morphologic transformation) and in the absence (to study spontaneous transformation) of asbestos. It was shown that spontaneous transformation of RPMC slightly accelerated in the co-cultures, whereas asbestos-induced transformation was strongly inhibited. For instance, RPMC acquired the ability to form multilayer cell growth foci and colonies in semisolid agar at 22-24 passages in the absence and at 14-16 passages in the presence of asbestos, while in co-culture with macrophages these signs of transformation appeared at 17-19 passages without asbestos treatment and were not observed at the 40th passage under exposure to asbestos. It was shown that the observed inhibition of transformation was caused by preferential depletion of transformed cells in co-cultures of mesothelium and macrophages in the presence of asbestos: when equal concentrations of macrophages and asbestos were taken, the viability of early-passage RPMC was greater as compared with late passages, and the viability of late-passage RPMC was greater than that of mesothelioma cells. The amount of late-passage RPMC and mesothelioma cells able to form colonies in semisolid media was also drastically decreased in these conditions. These findings suggest that though macrophages can influence the process of asbestos-induced mesothelium transformation by different ways, as a whole the inhibitory action appears to be the strongest.}, } @article {pmid11745800, year = {2001}, author = {Merritt, N and Blewett, CJ and Miller, JD and Bennett, WF and Young, JE and Urschel, JD}, title = {Survival after conservative (palliative) management of pleural malignant mesothelioma.}, journal = {Journal of surgical oncology}, volume = {78}, number = {3}, pages = {171-174}, doi = {10.1002/jso.1143}, pmid = {11745800}, issn = {0022-4790}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Mesothelioma/*mortality/therapy ; Middle Aged ; *Palliative Care ; Pleural Neoplasms/*mortality/therapy ; Retrospective Studies ; Survival Analysis ; }, abstract = {BACKGROUND AND OBJECTIVES: Malignant mesothelioma is a lethal disease. Aggressive multimodality treatment protocols are reportedly associated with improved survival, but the apparent survival benefits may simply reflect patient selection and the variable natural history of this malignancy. Before embarking on our own protocol of experimental treatment for mesothelioma, we sought to identify important prognostic factors and document the survival of patients treated conservatively (with palliative intent only) in our region.

METHODS: We performed a retrospective review of all patients with a diagnosis of malignant mesothelioma seen at our center between 1987 and 1999. Since curative intent treatment had not been given, we assumed that measured survival would largely reflect the natural history of the malignancy.

RESULTS: There were 101 patients (80 males and 21 females). Mean age was 65 +/- 9.2 years. Symptoms of disease were present for a median time of 5 months before the diagnosis was established. The most common presenting symptoms were dyspnea (46 patients), chest pain (30 patients), and weight loss (22 patients). Sixty-eight patients (68%) had a history of asbestos exposure. Mesothelioma subtypes included epithelial (43 patients), sarcomatous (26 patients), mixed (19 patients), desmoplastic (4 patients), and unspecified (9 patients). All 101 patients were treated with palliative intent. Talc pleurodesis was performed in 70 patients. At the time of analysis, 90 patients had died and 11 remained alive. Median survival was 213 (95% CI 137-289) days. Survival for the three major histological subtypes was significantly different (log rank, P = 0.0016). Histological subtype (epithelial favorable) was the only significant independent prognostic factor (Cox proportional hazard regression, P = 0.0009).

CONCLUSIONS: Patients with epithelial mesothelioma survive longer than those with other histological subtypes. Conservatively managed patients with pleural malignant mesothelioma have a median survival of approximately 7 months. These data from conservatively treated patients can serve as baseline information for future studies of experimental treatments.}, } @article {pmid11735696, year = {2001}, author = {Dessy, E and Falleni, M and Braidotti, P and Del Curto, B and Panigalli, T and Pietra, GG}, title = {Unusual clear cell variant of epithelioid mesothelioma.}, journal = {Archives of pathology & laboratory medicine}, volume = {125}, number = {12}, pages = {1588-1590}, doi = {10.5858/2001-125-1588-UCCVOE}, pmid = {11735696}, issn = {0003-9985}, mesh = {Biomarkers, Tumor/analysis ; Calbindin 2 ; Desmosomes/ultrastructure ; Diagnosis, Differential ; Epithelioid Cells/chemistry/*pathology ; Fatal Outcome ; Humans ; Immunoenzyme Techniques ; Male ; Mesothelioma/chemistry/*pathology/surgery ; Microscopy, Electron ; Microvilli/ultrastructure ; Middle Aged ; Pleural Effusion, Malignant/etiology/pathology ; Pleural Neoplasms/chemistry/*pathology/surgery ; S100 Calcium Binding Protein G/analysis ; }, abstract = {Clear cell mesothelioma is an extremely rare neoplasm of the pleura, which can easily be mistaken for a metastasis of clear cell carcinoma to the pleura. We report here the histochemical, immunohistochemical, and ultrastructural aspects of a new case of clear cell pleural mesothelioma in a 52-year-old man with no known asbestos exposure. He was admitted to the hospital for recurrent pleural effusion, which was negative for neoplastic cells at the cytologic examination. A partial decortication of the right pleura was performed. The morphologic, immunohistochemical, and ultrastructural features reported for this case are consistent with the diagnosis of clear cell mesothelioma. The differential diagnosis and immunohistochemical features in comparison with other clear cell neoplasms are discussed.}, } @article {pmid11725357, year = {2001}, author = {Scattone, A and Pennella, A and Giardina, C and Marinaccio, M and Ricco, R and Pollice, L and Serio, G}, title = {[Polycystic mesothelioma of the peritoneum. Description of 4 cases].}, journal = {Pathologica}, volume = {93}, number = {5}, pages = {549-555}, pmid = {11725357}, issn = {0031-2983}, mesh = {Abdominal Pain/etiology ; Adult ; Biomarkers, Tumor/analysis ; Child, Preschool ; Diagnosis, Differential ; Female ; Gilbert Disease/complications ; Humans ; Male ; Mesothelioma, Cystic/complications/*pathology/surgery ; Middle Aged ; Peritoneal Neoplasms/complications/*pathology/surgery ; Pregnancy ; Pregnancy Complications, Neoplastic/pathology/surgery ; }, abstract = {Cystic mesothelioma is a rare tumor of the peritoneal cavity arising from mesothelial cells. About 130 cases have been reported in the literature. The tumor is more frequent (85%) in adult women and rarely occurs in children. It is benign but recurrences are often described. The differential diagnosis with adenomatoid tumors, lymphangiomas, cystic malignant mesotheliomas and metastatic serous cystic tumors of the ovary is supported by immunohistochemistry. We describe four cases of cystic mesothelioma of the peritoneum; two of the cases occurred in pregnant women, one in a 45-year-old man and one in a 5-year-old boy. Asbestos exposure was not documented. The mesothelial origin of the neoplasms was supported by immunohistochemical analysis. Furthermore, tests for simian virus 40 (SV40 T antigen), to determine whether this virus was also present in the lesions, were negative.}, } @article {pmid11721205, year = {2001}, author = {Rena, O and Oliaro, A}, title = {[Malignant pleural mesothelioma].}, journal = {Minerva chirurgica}, volume = {56}, number = {6}, pages = {611-641}, pmid = {11721205}, issn = {0026-4733}, mesh = {Humans ; *Mesothelioma/diagnosis/epidemiology/etiology/therapy ; *Pleural Neoplasms/diagnosis/epidemiology/etiology/therapy ; Prognosis ; }, abstract = {Malignant pleural mesothelioma is a severe disease closely associated with asbestos exposure, at work or environmental. Its incidence has risen for some decades and it's expected to peak between 2010 and 2020. Up today, no treatment has been demonstrated as effective in influencing disease-related survival and the median prognosis ranges between 9 and 17 months after the diagnosis. The epithelial subtype of the disease seems to have a better prognosis when early diagnosed and treated with intrapleural immunotherapy or multimodality therapy. The diagnosis of the disease, often by exclusion, is obtained after macroscopic sampling of the pathological tissue, best accomplished by thoracoscopy, which also allows the intracavitary evaluation of the extension of the disease. Chemotherapy and radiotherapy alone didn't demonstrate any efficacy on the patient survival. For the early-stage disease (stage I) a therapeutic approach seems to be neoadjuvant intrapleural treatment using cytokines. For more advanced disease (stages II and III) resectability should be discussed with the thoracic surgeons and a multimodality treatment combining surgery, radiotherapy and chemotherapy should be proposed. This multimodality protocol has proved to be effective in patients with epithelial subtype, negative margins of resection and negative lymph nodes.}, } @article {pmid11712816, year = {2001}, author = {Melato, M and Rizzardi, C}, title = {Malignant pleural mesothelioma following chemotherapy for breast cancer.}, journal = {Anticancer research}, volume = {21}, number = {4B}, pages = {3093-3096}, pmid = {11712816}, issn = {0250-7005}, mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/*adverse effects/therapeutic use ; Asbestos ; Bone Neoplasms/secondary ; Breast Neoplasms/*drug therapy ; Cyclophosphamide/administration & dosage/adverse effects ; Environmental Exposure ; Epirubicin/administration & dosage/adverse effects ; Female ; Humans ; Incidence ; Italy/epidemiology ; Lung/chemistry/pathology ; Mesothelioma/epidemiology/*etiology ; Neoplasms, Second Primary/*etiology ; Pleural Effusion, Malignant/etiology ; Pleural Neoplasms/epidemiology/*etiology ; Time Factors ; }, abstract = {Although the induction of malignant mesothelioma by radiotherapy, used alone or in combination with chemotherapy, has been previously reported in the literature, the number of documented cases is extremely small. We report a case of malignant pleural mesothelioma arising four years after chemotherapy for breast cancer in a 42-year-old woman without a history of exposure to asbestos. To our knowledge, this is the f rst reported case of malignant pleural mesothelioma following treatment with chemotherapy alone. It is of interest not only for the patient's young age and the absence of exposure to asbestos, but also for the very short latency period, if compared with asbestos-related mesothelioma.}, } @article {pmid11707487, year = {2001}, author = {Bridgman, S}, title = {Community health risk assessment after a fire with asbestos containing fallout.}, journal = {Journal of epidemiology and community health}, volume = {55}, number = {12}, pages = {921-927}, pmid = {11707487}, issn = {0143-005X}, mesh = {Asbestos/*adverse effects/analysis ; Asbestos, Amosite/adverse effects ; Asbestos, Serpentine/adverse effects ; England ; Environmental Exposure ; Environmental Pollutants/*adverse effects/analysis ; *Fires ; Humans ; Industry ; Linear Models ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Risk Assessment ; Survival Rate ; }, abstract = {BACKGROUND: A factory fire in Tranmere, Merseyside, England, deposited asbestos containing fallout in an urban area. There was considerable community anxiety for months after the incident. Therefore an assessment of the long term health risks of this acute environmental incident were requested by the local health authority.

METHODS: The facts of the incident were gathered and appraised from unpublished and press reports, involved personnel, and further analysis of material collected at the time of the incident. The literature on the long term health risks of asbestos was reviewed, and combined with evidence on asbestos exposure to estimate community health risk.

RESULTS: Risk was almost entirely from exposure to fire fallout of chrysotile in asbestos bitumen paper covering the factory roof. Amosite was only detected in a few samples and in trace amounts. The number of people who lived in the area of fallout was 16 000 to 48 000. From a non-threshold model with assumptions likely to overestimate risk, the lung cancer risk is estimated to be undetectably small. Risk of mesothelioma from chrysotile exposure, and risks of lung cancer and mesothelioma from amosite exposure were based on observational studies and were estimated to be even lower than that of lung cancer risk from chrysotile exposure. Academically, there are assumptions that while reasonable cannot be proven, for example, the validity of extrapolating observed risk from much higher exposures to lower exposures, estimates of individual exposure, and that there is no threshold for asbestos to cause cancer.

CONCLUSIONS: The author is unaware of a similar study on long term health risks in a community exposed to asbestos in a fire. It is concluded that, using methods that do not underestimate risk, risk is undetectably small. Practical lessons from this methodology and approach to health risk assessment are discussed.}, } @article {pmid11688466, year = {2001}, author = {Butnor, KJ and Sporn, TA and Hammar, SP and Roggli, VL}, title = {Well-differentiated papillary mesothelioma.}, journal = {The American journal of surgical pathology}, volume = {25}, number = {10}, pages = {1304-1309}, doi = {10.1097/00000478-200110000-00012}, pmid = {11688466}, issn = {0147-5185}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/analysis ; Biomarkers, Tumor/analysis ; Female ; Humans ; Immunoenzyme Techniques ; Lung/chemistry ; Male ; Mesothelioma/chemistry/etiology/*pathology ; Middle Aged ; Peritoneal Neoplasms/chemistry/etiology/*pathology ; Pleural Neoplasms/chemistry/etiology/*pathology ; Testicular Neoplasms/chemistry/etiology/*pathology ; }, abstract = {Well-differentiated papillary mesothelioma is an unusual variant of epithelial mesothelioma considered to be of low malignant potential. The majority of previously reported cases developed in the peritoneum of young women without a history of asbestos exposure. The authors report 14 cases of well-differentiated papillary mesothelioma, seven of which originated in the pleura, six in the peritoneum, and one in the tunica vaginalis. Eleven of the patients were male and three were female, with an average age at presentation of 58 years (range 32-82 years). Six of the patients had a quantifiable history of asbestos exposure. Of the nine cases with complete follow-up, six had clinically indolent disease, one showed resolution after adjuvant chemotherapy, one pursued an aggressive course, and one died of other causes. These findings indicate that well-differentiated papillary mesothelioma is a rare variant of mesothelioma with a variable clinical prognosis that is etiologically related to asbestos exposure in some cases.}, } @article {pmid11676187, year = {2001}, author = {Barbieri, PG and Lombardi, S and Candela, A and Pezzotti, C and Binda, I}, title = {[Incidence of malignant mesothelioma (1980-1999) and asbestos exposure in 190 cases diagnosed among residents of the province of Brescia].}, journal = {La Medicina del lavoro}, volume = {92}, number = {4}, pages = {249-262}, pmid = {11676187}, issn = {0025-7818}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Female ; Humans ; Incidence ; Italy ; Male ; Mesothelioma/*epidemiology/*etiology ; Middle Aged ; Occupational Exposure/*statistics & numerical data ; Peritoneal Neoplasms/*epidemiology/*etiology ; Pleural Neoplasms/*epidemiology/*etiology ; }, abstract = {Several cases of malignant mesothelioma (MM) previously unknown to the Occupational Health and Safety Service were recognised in the Province of Brescia after an active surveillance program carried out during the first nineteen years of operation; a large proportion of the cases involved workers occupationally exposed to asbestos. A local Mesothelioma Register was subsequently set up in 1993 and by the end of 1999, 190 MM cases had been collected. The annual incidence ratio (standardized on the Italian population, census 1981, x100,000 person-years) was calculated in the 1980-1999 period and showed an increasing trend for location in the pleura in both sexes; in the 1996-1999 period the incidence ratio was 2.95 for males and 1.35 for females. In the same period, this trend was not observed for peritoneal location, with an incidence ratio of 0.17 and 0.37 for males and females respectively. 161 pleural MM (84.7%) and 28 peritoneal MM (14.7%) are described; histopathologic diagnosis was performed in 161 cases (84.7%). Anamneses were collected for 88% of the cases but with direct information from patients only in 65% of these in the recent period. Only 7 cases of asbestosis were diagnosed in the MM cases, whereas 31 cases of pleural abnormalities were observed but only 17 of these were observed in workers occupationally exposed to asbestos. Occupational asbestos exposure was evaluated as certain, probable or possible in 45% of total cases and in 54% of recently (1996-1999) observed cases, which were ten times more frequent in males. Exposure occurred in sectors works where asbestos was not used as raw material, such as construction, iron and steel and metal working. MM's from environmental and non-occupational exposure to asbestos were very few, 1.5% and 0.5% respectively. In 65 MM's asbestos exposure was unknown (34.2%); 50% of these concerned females; for whom the industry and jobs are discussed. The distribution of histologic types of MM was similar in asbestos exposed and non exposed cases. No association between peritoneal mesotheliomas and heavy exposure to asbestos was observed. Ten cases of MM were diagnosed in subjects under 45 years old (5.2%) with only one case occupationally exposed. 2 cases were exposed to radiation therapy (1%) and 2 cases to thoracic trauma (1%). Although in Italy MM has been included in the list of compensatable occupational diseases by law since 1994, a large number of cases occupationally exposed to asbestos are still not recognised by the National Insurance Institute (INAIL). A number of problems limiting work of the Mesothelioma Register and its usefulness are discussed. The Lombardy Mesothelioma Register set up in January 2000 should be able to overcome the limits identified in the past.}, } @article {pmid11673120, year = {2001}, author = {Magnani, C and Dalmasso, P and Biggeri, A and Ivaldi, C and Mirabelli, D and Terracini, B}, title = {Increased risk of malignant mesothelioma of the pleura after residential or domestic exposure to asbestos: a case-control study in Casale Monferrato, Italy.}, journal = {Environmental health perspectives}, volume = {109}, number = {9}, pages = {915-919}, pmid = {11673120}, issn = {0091-6765}, mesh = {Aged ; Asbestos/*adverse effects ; Carcinogens/*adverse effects ; Case-Control Studies ; *Environmental Exposure ; Female ; Housing ; Humans ; Italy/epidemiology ; Male ; Mesothelioma/epidemiology/*etiology ; Middle Aged ; Pleural Neoplasms/epidemiology/*etiology ; Risk Assessment ; }, abstract = {The association of malignant mesothelioma (MM) and nonoccupational asbestos exposure is currently debated. Our study investigates environmental and domestic asbestos exposure in the city where the largest Italian asbestos cement (AC) factory was located. This population-based case-control study included pleural MM (histologically diagnosed) incidents in the area in 1987-1993, matched by age and sex to two controls (four if younger than 60). Diagnoses were confirmed by a panel of five pathologists. We interviewed 102 cases and 273 controls in 1993-1995, out of 116 and 330 eligible subjects. Information was checked and completed on the basis of factory and Town Office files. We adjusted analyses for occupational exposure in the AC industry. In the town there were no other relevant industrial sources of asbestos exposure. Twenty-three cases and 20 controls lived with an AC worker [odds ratio (OR) = 4.5; 95% confidence interval (CI), 1.8-11.1)]. The risk was higher for the offspring of AC workers (OR = 7.4; 95% CI, 1.9-28.1). Subjects attending grammar school in Casale also showed an increased risk (OR = 3.3; 95% CI, 1.4-7.7). Living in Casale was associated with a very high risk (after selecting out AC workers: OR = 20.6; 95% CI, 6.2-68.6), with spatial trend with increasing distance from the AC factory. The present work confirms the association of environmental asbestos exposure and pleural MM, controlling for other sources of asbestos exposure, and suggests that environmental exposure caused a greater risk than domestic exposure.}, } @article {pmid11603959, year = {2001}, author = {Wong, O}, title = {Malignant mesothelioma and asbestos exposure among auto mechanics: appraisal of scientific evidence.}, journal = {Regulatory toxicology and pharmacology : RTP}, volume = {34}, number = {2}, pages = {170-177}, doi = {10.1006/rtph.2001.1491}, pmid = {11603959}, issn = {0273-2300}, mesh = {Asbestos/analysis/*toxicity ; Automobiles ; Carcinogens/analysis/*toxicity ; Mesothelioma/*chemically induced/*epidemiology ; *Occupational Exposure ; United States ; United States Environmental Protection Agency ; }, abstract = {In 1986 the U.S. Environmental Protection Agency (EPA) issued an official guideline on the prevention of asbestos disease among auto mechanics. In the EPA guideline, malignant mesothelioma was listed as a consequence of exposure to asbestos fibers from brake linings and clutch facings among auto mechanics. EPA formulated its 1986 opinion by relying solely on a few outdated case reports and not on epidemiologic studies. A review of the literature indicates that there are six epidemiologic studies providing relevant information on malignant mesothelioma among auto mechanics. Three of the six studies had already been published by 1986, the year in which EPA issued its guideline. The results of the six studies were remarkably consistent in that all six studies reported no increased risk of malignant mesothelioma among auto mechanics. The relative risks reported in the six studies ranged from 0.62 to 1.00. Based on a meta-analysis of the combined data of all six studies consisting of approximately 1500 malignant mesothelioma cases, the mesothelioma relative risk for auto mechanics is 0.90 (95% confidence interval 0.66-1.23). An application of Hill's causation criteria to epidemiologic data of malignant mesothelioma among auto mechanics clearly demonstrates that auto mechanics do not have an increased risk of malignant mesothelioma as a result of exposure to asbestos fibers from brake linings and clutch facings. However, in spite of the scientific evidence, EPA has not modified or revised its 1986 guideline. Occupational regulatory policies and guidelines, when based on proper scientific evidence, are invaluable and can prevent avoidable diseases in workers or other exposed individuals in the general public. On the other hand, it is the regulators' responsibility to develop, modify, and revise policies and guidelines in accordance with the most relevant and the latest scientific data. In this instance EPA as a regulator has not fulfilled its responsibility of providing the most accurate and up-to-date information to the workers or the general public.}, } @article {pmid11601750, year = {2001}, author = {Metintas, M and Metintas, S and Ucgun, I and Gibbs, AR and Harmanci, E and Alatas, F and Erginel, S and Tel, N and Pasaoglu, O}, title = {Prognostic factors in diffuse malignant pleural mesothelioma: effects of pretreatment clinical and laboratory characteristics.}, journal = {Respiratory medicine}, volume = {95}, number = {10}, pages = {829-835}, doi = {10.1053/rmed.2001.1178}, pmid = {11601750}, issn = {0954-6111}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Analysis of Variance ; Asbestos ; Chest Pain/etiology ; Dyspnea/etiology ; Environmental Exposure ; Female ; Humans ; Lung Neoplasms/complications/*mortality/pathology ; Male ; Mesothelioma/complications/*mortality/pathology ; Middle Aged ; Prognosis ; Proportional Hazards Models ; Regression Analysis ; Sex Factors ; Smoking/adverse effects ; Survival Rate ; Time Factors ; Weight Loss ; }, abstract = {The aim of this study was to investigate the effects of various pretreatment clinical and laboratory characteristics on the survival of patients with diffuse malignant pleural mesothelioma (DMPM). One hundred histopathologically confirmed DMPM patients were evaluated. Fifty-nine were treated with chemoimmunotherapy while 41 who had refused chemoimmunotherapy received supportive therapy alone. The following pretreatment characteristics were evaluated in both univariate and multivariate Cox regression analyses: age, gender, Karnofsky performance score (KPS), histology asbestos exposure, presence of chest pain, dyspnoea, weight loss, symptom duration, smoking history, disease location, platelet count, haemoglobin, white blood cell (WBC) count, serum lactate dehydrogenase (LDH) and extent of disease (stage). Univariate analysis showed that patients with age > or = 75 years, male gender, smoking history advanced stages above stage I disease, KPS < 70, WBC count > or = 8450 and LDH level > or = 500 IU l(-1) have a worse prognosis. With multivariate Cox regression analyses, age > or = 75 years, advanced stages above stage I disease, KPS < 70 and LDH level > or = 500 IU l(-1) were found to be indicators of a poorer prognosis. In conclusion, in our study each of low performance status, older age, advanced stage disease, high LDH level and prognosis were found to be related.}, } @article {pmid11598986, year = {2001}, author = {Ascoli, V and Calisti, R and Carnovale-Scalzo, C and Nardi, F}, title = {Malignant pleural mesothelioma in bakers and pastry cooks.}, journal = {American journal of industrial medicine}, volume = {40}, number = {4}, pages = {371-373}, doi = {10.1002/ajim.1111}, pmid = {11598986}, issn = {0271-3586}, mesh = {Aged ; Asbestos/adverse effects ; *Cooking ; Female ; Humans ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Diseases/*epidemiology/etiology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*epidemiology/etiology ; }, abstract = {BACKGROUND: The occurrence of malignant pleural mesothelioma (MPM) among bakers and pastry cooks has never been documented.

CASE REPORTS: We detected eight cases of MPM in bakers, pastry cooks, and biscuit cooks engaged in making, baking/cooking, and selling pastry/bread in two hospital-based series (Rome and Orbassano/Turin, Italy; period 1990-1997; 222 cases). Field-investigations revealed asbestos-containing material (ACM) in ovens for baking bread, that were manufactured prior to the 1980s.

CONCLUSIONS: It is suggested that there is a possible new association of the risk of having worked as a baker or pastry cook and MPM. Presumptive source of exposure to asbestos was the use of asbestos-insulated ovens.}, } @article {pmid11583654, year = {2001}, author = {McDonald, JC and Edwards, CW and Gibbs, AR and Lloyd, HM and Pooley, FD and Ross, DJ and Rudd, RM}, title = {Case-referent survey of young adults with mesothelioma: II. Occupational analyses.}, journal = {The Annals of occupational hygiene}, volume = {45}, number = {7}, pages = {519-523}, pmid = {11583654}, issn = {0003-4878}, mesh = {Adult ; Asbestos/*adverse effects/analysis ; Case-Control Studies ; Female ; Humans ; Lung Neoplasms/epidemiology/*etiology ; Male ; Mesothelioma/epidemiology/*etiology ; Microscopy, Electron ; Middle Aged ; Mineral Fibers/adverse effects/analysis ; Occupational Diseases/epidemiology/*etiology ; *Occupations ; Odds Ratio ; Risk Factors ; }, abstract = {OBJECTIVES: Our study aimed to identify occupations at increased risk of developing mesothelioma in persons aged 50 yr or less, and to relate these occupations to lung tissue concentration of asbestos fibres by type. In this age group it was thought that most, but not all, work-related exposures would have been since 1970, when the importation of crocidolite, but not amosite, was virtually eliminated.

METHODS: Eligible cases were sought from recent reports by chest physicians to the SWORD occupational disease surveillance scheme. Work histories were obtained for 115 men and 13 women, usually with the help of the chest physicians or coroners. Jobs were coded by the Office of National Statistics, so that the observed years spent in each occupation could be compared with expected values from census data, 1960-90. Lung tissue samples were obtained at autopsy from 69 male and four female cases, and mineral fibres identified, sized and counted by electron microscopy.

RESULTS: Of 37 industrial occupations analysed, odds ratios were significantly raised in eight: five in the construction industry and the others in shipbuilding, the manufacture of cement products and the manufacture of non-metallic mineral products (including asbestos). The concentrations in lung of crocidolite and amosite fibres, which together could account for 80-90% of cases, did not differ between occupational categories; those for amosite were appreciably higher than for crocidolite. Tremolite fibres were rarely found.

CONCLUSION: Mesothelioma in this young age group is dominated by carpenters, plumbers, electricians and insulators in the construction industry, and is mainly attributable to amphibole exposure. Work in shipbuilding and manufacture of mineral products was less important than in earlier studies. Contrary to expectation, however, some 90% of cases were in men who had started work before 1970.}, } @article {pmid11583653, year = {2001}, author = {McDonald, JC and Armstrong, BG and Edwards, CW and Gibbs, AR and Lloyd, HM and Pooley, FD and Ross, DJ and Rudd, RM}, title = {Case-referent survey of young adults with mesothelioma: I. Lung fibre analyses.}, journal = {The Annals of occupational hygiene}, volume = {45}, number = {7}, pages = {513-518}, pmid = {11583653}, issn = {0003-4878}, mesh = {Adult ; Asbestos/*adverse effects/analysis ; Case-Control Studies ; Female ; Humans ; Linear Models ; Logistic Models ; Lung Neoplasms/epidemiology/*etiology ; Male ; Mesothelioma/epidemiology/*etiology ; Microscopy, Electron ; Middle Aged ; Mineral Fibers/adverse effects/analysis ; Occupational Diseases/epidemiology/*etiology ; Risk Factors ; }, abstract = {OBJECTIVES: Our study aimed to determine the lung tissue concentration of asbestos and other mineral fibres by type and length in persons with mesothelioma aged 50 yr or less at time of diagnosis, compared to controls of similar age and geographical region. In this age group it was thought that most, but not all, work-related exposures would have been since 1970, when the importation of crocidolite, but not amosite, was virtually eliminated.

METHODS: Eligible cases were sought from recent reports by chest physicians to the SWORD occupational disease surveillance scheme. Lung tissue samples were obtained at autopsy from 69 male and four female cases, and mineral fibres identified, sized and counted by electron microscopy. Fibre concentrations per microg dry tissue were compared with similar estimates from a control series of autopsies of sudden or accidental deaths. Unadjusted, and adjusted odds ratios calculated by logistic regression, assessed relative risk in relation to fibre type, length and concentration.

RESULTS: Unadjusted and adjusted odds ratios increased steadily with concentration of crocidolite, amosite, tremolite and all amphiboles combined. There was also some increase with chrysotile, but well short of statistical significance. Incremental risk examined in a linear model was as highly significant for all amphiboles together as individually. Short, medium and long amphibole fibres were all associated with increased risk in relation to length. Mullite and iron fibres were significant predictors of mesothelioma when considered without adjustment for confounding by amphiboles, but, after adjustment, were weak and far from statistically significant.

CONCLUSIONS: In this young age group, amosite and crocidolite fibres could account for about 80% of cases of mesothelioma, and tremolite for some 7%. The contribution of chrysotile, because of low biopersistence, cannot be reliably assessed at autopsy, but to the extent that tremolite is a valid marker, our results suggest that it was small. The steep linear trend in odds ratio shown by amphiboles combined indicates that their effects may be additive, with increased risk from the lowest detectable fibre level. Non-asbestos mineral fibres probably made no contribution to this disease. Contrary to expectation, however, some 90% of cases were in men who had started work before 1970; this was so whether or not amosite or crocidolite was found in lung tissue.}, } @article {pmid11571739, year = {2001}, author = {Bongiovanni, M and Cassoni, P and De Giuli, P and Viberti, L and Cappia, S and Ivaldi, C and Chiusa, L and Bussolati, G}, title = {p27(kip1) immunoreactivity correlates with long-term survival in pleural malignant mesothelioma.}, journal = {Cancer}, volume = {92}, number = {5}, pages = {1245-1250}, doi = {10.1002/1097-0142(20010901)92:5<1245::aid-cncr1444>3.0.co;2-g}, pmid = {11571739}, issn = {0008-543X}, mesh = {Adult ; Aged ; Antigens, Nuclear ; Cell Cycle Proteins/*metabolism ; Cyclin-Dependent Kinase Inhibitor p27 ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen/metabolism ; Male ; Mesothelioma/*metabolism/mortality/pathology ; Middle Aged ; Nuclear Proteins/metabolism ; Pleural Neoplasms/*metabolism/mortality/pathology ; Survival Analysis ; *Tumor Suppressor Proteins ; }, abstract = {BACKGROUND: Pleural malignant mesothelioma (PMM) is a rare and highly aggressive tumor, whose development is strictly related to occupational exposure to asbestos. The prognosis of PMM is generally poor (median survival, 4-12 months), but a few have a relatively long survival. The objective of this study was to evaluate the use of the cell cycle-related proteins p27(kip1) and MIB-1 as prognostic indicators of survival in PMMs.

METHODS: Of 621 PMMs, the authors selected 27 cases with a relatively long-term survival (> 24 months) and a control group of 36 PMMs having a shorter (usual) survival (< 24 months).

RESULTS: The expression of the p27(kip1) was significantly higher in the long-term survival group compared with the control (short survival) group (81.41% vs. 31.94%; P < 0.0001). The PMMs of epithelioid histotype had a significantly higher p27(kip1) immunoreactivity compared with those of biphasic type (59.24% vs. 38.94%; P = 0.02). In agreement with the data in the literature, the proliferative activity (as detected by MIB-1 immunoreactivity) was significantly higher in short than long survival PMMs (43.53% vs. 14.11%; P < 0.0001) and in the biphasic histotype than in the epithelioid type (43.19% vs. 26.02%; P = 0.006).

CONCLUSIONS: The combined expression of high/low p27(kip1) and low/high Ki-67 values identified with 100% specificity and sensitivity long versus short survivors. p27(kip1) represents a reliable additional predictive factor for PMMs and a useful marker to identify patients having a more favorable prognosis.}, } @article {pmid11564223, year = {2001}, author = {Okamura, H and Kamei, T and Mitsuno, A and Hongo, H and Sakuma, N and Ishihara, T}, title = {Localized malignant mesothelioma of the pleura.}, journal = {Pathology international}, volume = {51}, number = {8}, pages = {654-660}, doi = {10.1046/j.1440-1827.2001.01250.x}, pmid = {11564223}, issn = {1320-5463}, mesh = {Brain Neoplasms/*secondary ; Humans ; Immunohistochemistry ; Japan ; Magnetic Resonance Angiography ; Male ; Mesothelioma/*pathology ; Middle Aged ; Pleural Neoplasms/*pathology ; }, abstract = {We describe a case of malignant pleural mesothelioma appearing as a solitary pleural tumor in a 56-year-old Japanese man with no history of exposure to asbestos. A chest radiograph revealed an isolated extrapulmonary mass in the left hemithorax. The patient underwent tumor resection, but the tumor later recurred on the contralateral pleura. The patient developed cerebral metastases and died 16 months after the initial surgery. The resected tumor was sessile with broad-based pleural attachment. Microscopically, the tumor was composed of interlacing fascicles of plump spindle cells intermixed with few polygonal cells. Most of the tumor cells showed positive immunoreactivity for cytokeratins (AE1 and AE3) and vimentin. Many of the tumor cells were positive for epithelial membrane antigen, and a few were positive for desmin. In contrast, the tumor cells were consistently negative for carcinoembryonic antigen, epithelial antigen BerEP4, calretinin, S-100 protein, neuron-specific enolase, muscle actin antigen HHF35, alpha-smooth muscle actin antigen and CD34. Ultrastructurally, the tumor cells had diffusely distributed cytoplasmic intermediate filaments, desmosome-like junctions, and a few microvilli. Some tumor cells contained cytoplasmic tonofilaments. Immunohistochemical and ultrastructural findings supported the mesothelial nature of the tumor, and led us to diagnose this tumor as a sarcomatoid localized malignant mesothelioma.}, } @article {pmid11563601, year = {2001}, author = {Neumann, V and Günthe, S and Mülle, KM and Fischer, M}, title = {Malignant mesothelioma--German mesothelioma register 1987-1999.}, journal = {International archives of occupational and environmental health}, volume = {74}, number = {6}, pages = {383-395}, doi = {10.1007/s004200100240}, pmid = {11563601}, issn = {0340-0131}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Female ; Germany/epidemiology ; Humans ; Male ; Mesothelioma/chemically induced/*epidemiology/therapy ; Middle Aged ; Occupational Exposure/*adverse effects ; Pleura/pathology ; Pulmonary Fibrosis/chemically induced/epidemiology ; *Registries ; Survival Analysis ; }, abstract = {OBJECTIVES: The study group comprised a collective of 1,605 patients with malignant mesotheliomas and with lung tissue available for lung dust analyses.

METHOD: Clinical features, occupational histories, expositions and individual data were evaluated, and the asbestos bodies concentrations (asbestos bodies/cm3 lung tissue or g wet tissue) were determined.

RESULTS: Mesotheliomas developed mainly in men (94.5%). Of the cases, 96.4% were of pleural origin and only 3.3% were peritoneal mesotheliomas. The biphasic subtype predominated (61.3%), followed by the epithelioid type (29.3%). The sarcomatoid subtype was rarely developed (9.4%). Mean age at first diagnosis was 60.4 years. The mean survival time from time of symptom onset was 13.5 months. Patients with epithelioid subtypes had a longer survival time (16.9 months) than those with biphasic (13.1 months) and sarcomatoid subtypes (5.5 months). Of the patients, 73% presented pleural effusions as initial symptoms of the disease. An increased asbestos burden was identified by light microscopy in 84.8% of the patients. There was no association between histological subtypes and the asbestos burden of the lungs. Patients with peritoneal mesotheliomas had distinctly higher asbestos burdens in the lungs than patients with pleural mesotheliomas. There exists no association between lung asbestos burdens and survival times. The mean latency period was 37.8 years. A trend: higher asbestos burden of the lung/shorter latency periods was suggested. About 70% of the patients had a history of occupational exposure to asbestos dust. Most patients worked in the building trade, the locksmith and machine building industries and in the steel and blast-furnace industries. Of the patients, 25.6% had asbestos-associated lung fibroses, in 40.7% of the cases pleural plaques were identified.

CONCLUSIONS: The most important causal factor for development of mesotheliomas is still asbestos, primarily amphibole asbestos. The recurring occurrence of mesotheliomas in younger people without known asbestos exposure needs the urgent investigation of other inducing factors for mesotheliomas.}, } @article {pmid11561359, year = {2001}, author = {Marsh, GM and Gula, MJ and Youk, AO and Buchanich, JM and Churg, A and Colby, TV}, title = {Historical cohort study of US man-made vitreous fiber production workers: II. Mortality from mesothelioma.}, journal = {Journal of occupational and environmental medicine}, volume = {43}, number = {9}, pages = {757-766}, doi = {10.1097/00043764-200109000-00005}, pmid = {11561359}, issn = {1076-2752}, mesh = {Adult ; Cause of Death ; Cohort Studies ; Female ; Follow-Up Studies ; *Glass ; Humans ; Male ; Mesothelioma/*chemically induced/*mortality/pathology ; Middle Aged ; Occupational Diseases/chemically induced/mortality ; Occupational Exposure/*adverse effects ; Respiratory Tract Neoplasms/*chemically induced/*mortality ; Sex Factors ; Surveys and Questionnaires ; Survival Analysis ; Textiles/adverse effects ; United States/epidemiology ; }, abstract = {As part of our ongoing mortality surveillance program for the US man-made vitreous fiber (MMVF) industry, we examined mortality from malignant mesothelioma using data from our 1989 follow-up of 3478 rock/slag wool workers and our 1992 follow-up of 32,110 fiberglass workers. A manual search of death certificates for 1011 rock/slag wool workers and 9060 fiberglass workers revealed only 10 death certificates with any mention of the word "mesothelioma." A subsequent review of medical records and pathology specimens for 3 of the 10 workers deemed two deaths as definitely not due to mesothelioma and one as having a 50% chance of being caused by mesothelioma. Two other deaths, for which only medical records were available, were given less than a 50% chance of being due to mesothelioma. Eight of the 10 decedents had potential occupational asbestos exposure inside or outside the MMVF industry. We also estimated the mortality risk from malignant mesothelioma in the cohort using two cause-of-death categorizations that included both malignant and benign coding rubrics. Using the more comprehensive scheme, we observed overall deficits in deaths among the total cohort and fiberglass workers and an overall excess among rock/slag wool workers. The excess in respiratory system cancer is largely a reflection of elevated lung cancer risks that we attributed mainly to confounding by smoking, to exposures outside the MMVF industry to agents such as asbestos, or to one or more of the several co-exposures present in many of the study plants (including asbestos). The second scheme, which focused on pleural mesothelioma in time periods when specific malignant mesothelioma coding rubrics were available, classified only one cohort death as being caused by malignant mesothelioma, compared with 2.19 expected deaths (local county comparison). We conclude that the overall mortality risk from malignant mesothelioma does not seem to be elevated in the US MMVF cohort.}, } @article {pmid11551405, year = {2001}, author = {Emri, S and Akbulut, H and Zorlu, F and Dinçol, D and Akay, H and Güngen, Y and Içli, F}, title = {Prognostic significance of flow cytometric DNA analysis in patients with malignant pleural mesothelioma.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {33}, number = {2-3}, pages = {109-114}, doi = {10.1016/s0169-5002(00)00249-x}, pmid = {11551405}, issn = {0169-5002}, mesh = {Adult ; Aged ; Biomarkers, Tumor/analysis ; DNA, Neoplasm/*analysis ; Female ; Flow Cytometry ; Humans ; Male ; Mesothelioma/diagnosis/*genetics/therapy ; Middle Aged ; Pleural Neoplasms/diagnosis/*genetics/therapy ; Ploidies ; Prognosis ; Survival Analysis ; }, abstract = {Malignant pleural mesothelioma (MPM) due to environmental exposure to asbestos and erionite is a relatively common cancer in Turkey. In this study, we investigated the value of flow cytometric (FCM) DNA analysis and other prognostic factors such as age and etiologic factor in the patients with MPM, treated with surgery+/-combination chemotherapy+/-radiotherapy. A total of 40 patients with a median age of 50 (range 30-68) were included in the study. Twenty-nine patients had asbestos exposure in etiology, while 11 had fibrous zeolite (erionite). Paraffin-embedded tumor specimens were studied by FCM for DNA analysis. Twelve patients (30%) had aneuploid tumors and 28 (70%) had diploid ones. Mean S-phase fraction (SPF; %) was 9.1+/-1.1 and proliferation index (PI, SPF+G2/M phase; %) was 11.3+/-0.9. While the median overall survival (OS) was 10+/-2 months (6-14; 95% CI), 1-year survival rate was 45.2%. Only PI was found to be statistically significant for OS in univariate analysis (P=0.013). PI was also found to be an independent prognostic factor for all patients (P=0.035). Aneuploidy was significantly higher in erionite group compared with asbestos group. Male predominance and poor survival were also prominent in erionite group, though not statistically significant. In conclusion, PI is an independent prognostic factor for patients with MPM and the biologic features of the disease may show differences with respect to different etiologies.}, } @article {pmid11549559, year = {2001}, author = {Yano, E and Wang, ZM and Wang, XR and Wang, MZ and Lan, YJ}, title = {Cancer mortality among workers exposed to amphibole-free chrysotile asbestos.}, journal = {American journal of epidemiology}, volume = {154}, number = {6}, pages = {538-543}, doi = {10.1093/aje/154.6.538}, pmid = {11549559}, issn = {0002-9262}, mesh = {Age Factors ; Aged ; Asbestos/*adverse effects ; Carcinogens/*adverse effects ; Cohort Studies ; Humans ; Incidence ; Lung Neoplasms/*etiology/mortality ; Male ; Mesothelioma/*etiology/mortality ; Middle Aged ; *Occupational Exposure ; Risk Factors ; Smoking ; }, abstract = {The issue of whether exposure to chrysotile asbestos alone, without contamination from amphibole asbestos, causes lung cancer and mesothelioma was investigated in a 25-year longitudinal study (1972-1996) in Chongqin, China. The study cohort comprised 515 male asbestos plant workers exposed to chrysotile only; the control cohort included 650 non-dust-exposed workers. The results of analysis in which the proportional hazards model was used indicated that mortality due to all causes, all cancers, and lung cancer was related to asbestos exposure; the relative risks, adjusted for age and smoking, were 2.9, 4.3, and 6.6, respectively. Fiber concentrations in the raw material section and the textile section of the plant were 7.6 and 4.5 fibers/ml, respectively. Because of differences between the study and control plants, the authors also compared various sections of the asbestos plant that had different levels of dust exposure. The adjusted relative risk of lung cancer was 8.1 for workers exposed to high versus low levels of asbestos. Two cases of malignant mesothelioma, one pleural and the other peritoneal, were found in the asbestos cohort. These results suggest that heavy exposure to pure chrysotile asbestos alone, with negligible amphibole contamination, can cause lung cancer and malignant mesothelioma in exposed workers.}, } @article {pmid11547584, year = {2001}, author = {Aguilar Madrid, G}, title = {[Reconstruction of the exposure to asbestos in cases of pleural mesothelioma in Mexico].}, journal = {Salud publica de Mexico}, volume = {43}, number = {4}, pages = {263-265}, pmid = {11547584}, issn = {0036-3634}, mesh = {Asbestos/*adverse effects ; Humans ; Mesothelioma/*etiology ; Mexico ; *Occupational Exposure ; Pleural Neoplasms/*etiology ; }, } @article {pmid11533801, year = {2000}, author = {Al-Amri, SM and Rahmatulla, RH and Al-Bozom, IA}, title = {Malignant peritoneal mesothelioma.}, journal = {Saudi medical journal}, volume = {21}, number = {3}, pages = {291-293}, pmid = {11533801}, issn = {0379-5284}, mesh = {Abdominal Pain/etiology ; Anorexia/etiology ; Ascites/etiology ; Biopsy ; Humans ; Immunohistochemistry ; Laparoscopy ; Male ; Mesothelioma/complications/*pathology ; Middle Aged ; Peritoneal Neoplasms/complications/*pathology ; Prognosis ; Risk Factors ; Saudi Arabia ; Tomography, X-Ray Computed ; Weight Loss ; }, abstract = {Malignant peritoneal mesotheliomas are rare tumors arising from the peritoneal surface. We report a 53 year old, non-asbestos exposed Saudi male who presented with exudative ascites. The diagnosis was obtained from laparoscopic biopsy. To the best of our knowledge this entity has not been described in the Saudi community. The aim is to increase the awareness among the medical community about this rare entity.}, } @article {pmid11530960, year = {2001}, author = {Olut, A and Firat, P and Ertugrul, D and Gungen, Y and Emri, S}, title = {Ras oncoprotein expression in erionite- and asbestos-induced Turkish malignant pleural mesothelioma patients--a pilot study.}, journal = {Respiratory medicine}, volume = {95}, number = {8}, pages = {697-698}, doi = {10.1053/rmed.2001.1122}, pmid = {11530960}, issn = {0954-6111}, mesh = {*Asbestos ; Female ; Humans ; Immunohistochemistry ; Male ; Mesothelioma/*metabolism ; Middle Aged ; Pleural Neoplasms/*metabolism ; Proto-Oncogene Proteins p21(ras)/analysis ; Turkey ; *Zeolites ; ras Proteins/*analysis ; }, } @article {pmid11523570, year = {2001}, author = {Pujolar, AE and González, C and Agudo, A and Calleja, A and Beltrán, M and González-Moya, J and Hernandez, S and Panades, R and Ramirez, J and Turuguet, D}, title = {Information about occupational exposure to asbestos given to cases in an etiological study: ethical aspects.}, journal = {European journal of epidemiology}, volume = {17}, number = {1}, pages = {1-6}, pmid = {11523570}, issn = {0393-2990}, mesh = {*Asbestos ; Case-Control Studies ; *Ethics, Medical ; Humans ; Mesothelioma/*epidemiology ; *Occupational Exposure ; Pleural Neoplasms/*epidemiology ; }, abstract = {The aim of the study is to consider some ethical aspects of the provision of information, to the cases or their families, about the assessment of occupational asbestos exposure obtained in a case-control study of malignant mesothelioma of the pleura. An informative letter with the result of the evaluation of their occupational exposure to asbestos was sent to the participating cases (and/or their family). Those whose exposure was classified as certain/probable were also informed of the legislation regarding occupational diseases. Of the 132 cases, 32.6% of subjects and/or their families made telephone calls expressing interest in the content of the informative letter. Among the 63 cases classified as certain/probable exposure, this proportion was 47.6%. Out of 43 cases in which the age at diagnosis was < or = 65 years and the exposure to asbestos was certain/probable, only two (4.6%) were signed off work owing to occupational disease. Only one of the mesothelioma cases was recognized by the Spanish National Institute for Social Security (INSS) as having an occupational disease. The process of communication of the results of an epidemiological research should include the provision of information on the exposure data to each one of the subjects, and/or their families. There is a great disparity between the number of cases of certain/probable exposure to asbestos identified in our study, and the number registered as an occupational disease by the INSS.}, } @article {pmid11515151, year = {2001}, author = {Merler, E and Gioffrè, F and Rozio, L and Bizzotto, R and Mion, M and Sarto, F}, title = {[Pleural mesothelioma in women in the Veneto Region who used to work as rag sorters for textile recycling and paper production].}, journal = {La Medicina del lavoro}, volume = {92}, number = {3}, pages = {181-186}, pmid = {11515151}, issn = {0025-7818}, mesh = {Aged ; Female ; Humans ; Italy ; Mesothelioma/*epidemiology/pathology ; Middle Aged ; Occupational Diseases/*epidemiology/pathology ; Paper ; Pleural Neoplasms/*epidemiology/pathology ; Textiles ; Time Factors ; }, abstract = {The paper reports 9 cases of mesothelioma diagnosed by means of histology or cytology that were observed among women resident in the Veneto Region, Northern Italy, whose only activity that could involve exposure to asbestos was as rag sorter. These cases are part of a group of about 260 subjects with mesothelioma whose entire working and residential history has been collected. The women worked as rag sorters between the 1940's and 1960's in textile recycling (8 cases) or (one case) at a paper mill where cotton was used for paper production. The work as rag sorter helps to explain the high proportion of mesotheliomas among women with an occupational exposure to asbestos.}, } @article {pmid11513797, year = {2001}, author = {Rees, D and Phillips, JI and Garton, E and Pooley, FD}, title = {Asbestos lung fibre concentrations in South African chrysotile mine workers.}, journal = {The Annals of occupational hygiene}, volume = {45}, number = {6}, pages = {473-477}, pmid = {11513797}, issn = {0003-4878}, mesh = {Adult ; Aged ; Asbestos/analysis ; Asbestos, Amphibole/*analysis ; Asbestos, Serpentine/*analysis ; Humans ; Lung/*pathology ; Middle Aged ; Mineral Fibers/analysis ; *Mining ; South Africa ; }, abstract = {Mesothelioma has not been found in South African chrysotile miners and millers despite decades of producing about 100000 tons of the mineral per year. One possible explanation for the scarcity or absence of the cancer may be a relative lack of contaminating fibrous tremolite, an amphibole that variably occurs with chrysotile ores. The fibre content in the lungs of nine former chrysotile mine workers was ascertained by transmission electron microscopy. Despite fairly long service in most cases (median 9.5 yr; range 32-4 yr) the concentrations of chrysotile fibres were relatively low: only two cases exceeded 1.14 million fibres/g dried lung. Tremolite fibre levels were even lower: less than 1 million fibres/g dried lung in all but one case. Tremolite fibre concentrations exceeded those of chrysotile in only two cases. These results support the contention that South African chrysotile is not heavily contaminated by tremolite.}, } @article {pmid11510098, year = {2001}, author = {Tominaga, M and Tanaka, M and Fukuoka, M and Kawashima, M and Yatsunami, J and Nakahara, Y and Aoki, Y and Hayashi, S}, title = {[A case of desmoplastic malignant pleural mesothelioma].}, journal = {Nihon Kokyuki Gakkai zasshi = the journal of the Japanese Respiratory Society}, volume = {39}, number = {5}, pages = {347-350}, pmid = {11510098}, issn = {1343-3490}, mesh = {Aged ; Back Pain/etiology ; Female ; Humans ; Magnetic Resonance Imaging ; Mesothelioma/*diagnosis/pathology ; Neoplasm Invasiveness ; Pleural Neoplasms/*diagnosis/pathology ; Spinal Neoplasms/pathology ; Tomography, X-Ray Computed ; }, abstract = {A 71-year-old woman with no history of asbestos exposure was referred to our hospital for evaluation of mediastinal soft tissue density. Six months prior to the admission, she had developed back pain and had been diagnosed as having intercostal neuralgia. Since the symptoms progressed, she was referred to another hospital. While chest radiography revealed no abnormality, chest computed tomography showed the prominence of mediastinal soft tissue, extending to the left hilum and partially destroying the nearby vertebrae. However, no pleural effusion was noted. After admission, a thoracoscopic examination was performed, and a whitish mass was found on the pleural surface partially adhering to the chest wall. Histological examination of the biopsied material showed dense areas of collagenous tissue with small foci of slightly atypical spindle cells. These findings led to the diagnosis of desmoplastic malignant pleural mesothelioma. The patient was treated with combined chemo-radiotherapy, but the response to this treatment was unclear. To date, reports for this subgroup of malignant mesothelioma are still rare.}, } @article {pmid11501711, year = {2001}, author = {Weir, NA and Gerstenhaber, B}, title = {A case of pleural mesothelioma with effusive-constrictive pericarditis.}, journal = {The Yale journal of biology and medicine}, volume = {74}, number = {3}, pages = {159-163}, pmid = {11501711}, issn = {0044-0086}, mesh = {Aged ; Asbestos ; Environmental Exposure ; Humans ; Male ; Mesothelioma/complications/*diagnosis ; Pericarditis, Constrictive/complications/*diagnosis ; Pleural Neoplasms/complications/*diagnosis ; Tomography ; }, } @article {pmid11496551, year = {2001}, author = {Pérez Lorenz, JB and López Gracia, S and Pons, J and Marigil, M}, title = {[Peritoneal mesothelioma in a man who transported asbestos].}, journal = {Anales de medicina interna (Madrid, Spain : 1984)}, volume = {18}, number = {4}, pages = {225}, pmid = {11496551}, issn = {0212-7199}, mesh = {Asbestos/*adverse effects ; Fatal Outcome ; Humans ; Male ; Mesothelioma/diagnosis/*etiology ; Middle Aged ; Occupational Exposure/*adverse effects ; Peritoneal Neoplasms/diagnosis/*etiology ; }, } @article {pmid11494349, year = {2001}, author = {Rom, WN and Hammar, SP and Rusch, V and Dodson, R and Hoffman, S}, title = {Malignant mesothelioma from neighborhood exposure to anthophyllite asbestos.}, journal = {American journal of industrial medicine}, volume = {40}, number = {2}, pages = {211-214}, doi = {10.1002/ajim.1089}, pmid = {11494349}, issn = {0271-3586}, support = {M01 RR00096/RR/NCRR NIH HHS/United States ; }, mesh = {Adult ; Asbestos, Amphibole/*adverse effects ; Environmental Exposure/*adverse effects ; Humans ; Male ; Mesothelioma/*etiology ; Pleural Neoplasms/*etiology ; }, abstract = {BACKGROUND: Anthophyllite asbestos has been reported to cause asbestosis, lung cancer, mesothelioma, and pleural plaques in occupationally exposed workers. Anthophyllite has also been associated with pleural plaques in Finland and Japan among those who live near mines and mills and have neighborhood or environmental exposure.

METHODS: We evaluated a 38-year-old patient with pleural mesothelioma who lived, attended school, and delivered newspapers near a manufacturing facility that used exclusively anthophyllite asbestos fiber from ages 8-17 years. He had no work exposure to asbestos.

RESULTS: The pleural mesothelioma was an epithelial type with tubulopapillary structures and was treated with an extrapleural pneumonectomy followed by radiation therapy. The malignant cells were positive by immunohistochemistry for cytokeratin but negative for carcinoembryonic antigen, S100, B72.3, and leu M1 antigen. Anthophyllite fibers were > 5 microm in length in lung tissue compared to 3 microm from a general population study.

CONCLUSIONS: Anthophyllite asbestos has been associated with neighborhood environmental exposure and pleural plaques; we now report a neighborhood exposure and pleural mesothelioma.}, } @article {pmid11488327, year = {2001}, author = {Dumortier, P and Göcmen, A and Laurent, K and Manço, A and De Vuyst, P}, title = {The role of environmental and occupational exposures in Turkish immigrants with fibre-related disease.}, journal = {The European respiratory journal}, volume = {17}, number = {5}, pages = {922-927}, doi = {10.1183/09031936.01.17509220}, pmid = {11488327}, issn = {0903-1936}, mesh = {Adult ; Aged ; Asbestos, Amphibole/*adverse effects ; Asbestosis/*ethnology/etiology ; Belgium ; *Emigration and Immigration ; Environmental Exposure/*adverse effects ; Female ; Humans ; Male ; Mesothelioma/ethnology/etiology ; Middle Aged ; Mineral Fibers/*adverse effects ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/ethnology/etiology ; Pneumoconiosis/*ethnology/etiology ; Turkey/ethnology ; Zeolites/*adverse effects ; }, abstract = {Environmental exposure to tremolite and erionite causes endemic diseases of the lung and pleura in Turkey. This study aimed to evaluate the impact of these exposures and further occupational exposures on fibre-related diseases in Turkish immigrants living in Belgium. The study included 51 males and 17 females that emigrated < 1-38 yrs ago. Most of them (n=46) had nonmalignant pleural lesions, one had asbestosis and one had mesothelioma. Environmental asbestos exposure was likely for the majority of patients (60%), but there were also reports of possible occupational asbestos (n = 14) and erionite (n = 2) exposure. Tremolite was the main fibre type in bronchoalveolar lavage fluid (BALF). Elevated concentrations of amosite or crocidolite were detected in only two patients. The delay elapsed since the end of the environmental exposure had no influence on the asbestos body or the tremolite fibre concentrations in the BALF of Turkish immigrants. Most fibre-related diseases in Turkish immigrants are probably due to environmental rather than occupational exposure. Precise information about geographical origin and occupation should be obtained when investigating these patients. Mineralogical analysis of bronchoalveolar lavage fluid gives valuable information on the type and intensity of exposure, especially in patients with both environmental and occupational exposure.}, } @article {pmid11486477, year = {2001}, author = {Barth, Z and Thiele, H and Frenzel, H and Kohler, B}, title = {[A rare cause of malignant ascites--peritoneal mesothelioma].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {126}, number = {27}, pages = {779-782}, doi = {10.1055/s-2001-15558}, pmid = {11486477}, issn = {0012-0472}, mesh = {Antineoplastic Agents/therapeutic use ; Asbestos/adverse effects ; Ascites/*etiology ; Humans ; Immunohistochemistry ; Interferon-alpha/therapeutic use ; Laparoscopy ; Laparotomy ; Mesothelioma/*diagnosis/pathology/therapy ; Middle Aged ; Neoplasm Metastasis ; Occupational Exposure ; Peritoneal Neoplasms/*diagnosis/pathology/therapy ; Peritoneum/*pathology ; }, abstract = {HISTORY AND CLINICAL FINDINGS: A 56-year-old patient (case 1) with recurrent haemorrhagic ascites for one year was admitted to our hospital for further investigation. Besides massive ascites he did not show abnormal physical signs. In addition, two 45-year-old patients were admitted (case 2 and 3) with clinical signs of acute abdomen--one having muscular guarding in the epigastric angle, the other in the right lower quadrant. All 3 patients did not have serious illnesses in the past; the first 2 patients had occupational asbestos exposure.

INVESTIGATIONS: In patient 1 the ultrasound did not reveal abnormal findings besides ascites. Patients 2 and 3 underwent explorative laparotomy.

In the first case a diagnostic laparoscopy revealed diffuse tumor proliferations with nodular formations over the entire peritoneum--histologically a malignant peritoneal mesothelioma of the epithelial subtype. Patient 2 showed intraoperatively metastatic spread of tumour formations with infiltration of the peritoneum and transverse mesocolon. The histologic finding was similar to that in the first case. Patient 3 had a perforated sigma diverticulitis which was treated by resection of the sigmoid. Incidentally a well differentiated papillary peritoneal mesothelioma was found in the resected specimen. The first two patients were treated with alpha-interferon subcutaneously resulting in a decrease of ascites production. Because patient 3 showed neither ascites nor evidence for malignancy no interferon was administered.

CONCLUSION: In case of haemorrhagic ascites of unknown cause a histological clarification by either laparoscopy or laparotomy is mandatory. Immunomodulation with interferon may be a promising approach.}, } @article {pmid11466985, year = {2001}, author = {Kjaergaard, J and Andersson, M}, title = {[Incidence of malignant mesothelioma in Denmark and expected number of future cases among men].}, journal = {Ugeskrift for laeger}, volume = {163}, number = {27}, pages = {3779-3783}, pmid = {11466985}, issn = {0041-5782}, mesh = {Adult ; Aged ; Denmark/epidemiology ; Heart Neoplasms/*epidemiology ; Humans ; Incidence ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Pericardium/pathology ; Peritoneal Neoplasms/*epidemiology ; Pleural Neoplasms/*epidemiology ; Poisson Distribution ; Prognosis ; Registries ; Risk Factors ; }, abstract = {INTRODUCTION: The aim was to analyse incidence rates and to predict the future number of cases of malignant mesothelioma in Denmark.

METHODS: We analysed the 1912 cases of malignant mesothelioma reported to the Danish Cancer Register, 1943-1993, in order to describe the current incidence rates. The relative risks of synthetic birth cohorts were estimated by a Poisson regression model and used to predict the future number of cases in males.

RESULTS: The incidence rate increased to 1.33 per 100,000 person years in men in 1983-1987, and to 0.51 in women in 1973-1977. According to a Poisson regression model, the risk in birth cohorts in males peaked in the 1940-1944 cohort and decreased to 0.57 in the 1950-1954 cohort. The age-specific incidence rate peaked at 246 per 100,000 person years in the age group of 80-84. The future annual number of mesothelioma cases is expected to peak around 2015 with 93 cases in men born before 1955.

DISCUSSION: The fit of the model was not ideal, but with careful interpretation of the results we conclude that a further increase in the number of mesothelioma cases can be expected, and the effect of regulating the environmental exposure to asbestos cannot be expected within the next 10-15 years.}, } @article {pmid11454052, year = {2001}, author = {Monaghan, H and Al-Nafussi, A}, title = {Deciduoid pleural mesothelioma.}, journal = {Histopathology}, volume = {39}, number = {1}, pages = {104-106}, doi = {10.1046/j.1365-2559.2001.1217d.x}, pmid = {11454052}, issn = {0309-0167}, mesh = {Aged ; Asbestos/adverse effects ; Calbindin 2 ; Carcinogens/adverse effects ; Humans ; Immunohistochemistry ; Keratins/analysis ; Male ; Mesothelioma/chemically induced/metabolism/*pathology ; Pleural Neoplasms/chemically induced/metabolism/*pathology ; S100 Calcium Binding Protein G/analysis ; }, } @article {pmid11453316, year = {2001}, author = {Isik, R and Metintas, M and Gibbs, AR and Metintas, S and Jasani, B and Oner, U and Harmanci, E and Demircan, S and Işiksoy, S}, title = {p53, p21 and metallothionein immunoreactivities in patients with malignant pleural mesothelioma: correlations with the epidemiological features and prognosis of mesotheliomas with environmental asbestos exposure.}, journal = {Respiratory medicine}, volume = {95}, number = {7}, pages = {588-593}, doi = {10.1053/rmed.2001.1108}, pmid = {11453316}, issn = {0954-6111}, mesh = {Age Factors ; Asbestos, Amphibole/adverse effects ; Chi-Square Distribution ; Environmental Exposure/adverse effects ; Female ; Humans ; Male ; Mesothelioma/*chemistry/etiology ; Metallothionein/*analysis ; Middle Aged ; Occupational Exposure/adverse effects ; Oncogene Protein p21(ras)/*analysis ; Paraffin Embedding ; Pleural Neoplasms/*chemistry/etiology ; Prognosis ; Sex Factors ; Survival Analysis ; Tumor Suppressor Protein p53/*analysis ; }, abstract = {The aim of this study is to investigate immunoreactivity for p53, p21 and metallothionein in diffuse malignant pleural mesothelioma (DMPM) and to determine the relationships between the age, sex, asbestos exposure time, survival of DMPM patients with environmental asbestos exposure and immunoreactivity to p53, p21 and metallothionein. Sixty-seven histopathologically-confirmed DMPMs, 38 of whom had environmental and 29 had occupational asbestos exposure, were included. The tumour tissue samples were immunostained with antibodies against p53, p21 and metallothionein. Epidemiological data and the survival times for the DMPM patients with environmental asbestos exposures were obtained from hospital records. Thirty-three per cent of the DMPMs were positive for p53, 35% for p21 and 52% for metallothionein. There was no statistical difference between the histological subtypes of DMPM in terms of immunoreactivity for p53, p21 and metallothionein. For p21 and metallothionein there was a statistically significant difference between the exposure characteristics: patients with environmental asbestos exposure had shown more immunopositivity. There were statistically significant differences between age groups and between asbestos exposure times for metallothionein, and between asbestos exposure times and p21. The patients with positive immunostaining had longer exposure times and were older than those having negative immunostaining. The differences between survival of the patients were not statistically significant in terms of the immunohistochemical results for p53, p21 and metallothionein.}, } @article {pmid11436151, year = {2000}, author = {Murer, B}, title = {Pleural malignant mesothelioma.}, journal = {Advances in clinical pathology : the official journal of Adriatic Society of Pathology}, volume = {4}, number = {4}, pages = {177-179}, pmid = {11436151}, issn = {1125-5552}, mesh = {Asbestos/*adverse effects ; Diagnosis, Differential ; Humans ; Mesothelioma/*chemically induced/genetics/*pathology ; Pleural Neoplasms/*chemically induced/genetics/*pathology ; Prognosis ; }, } @article {pmid11423790, year = {2001}, author = {Melloni, G and Puglisi, A and Ferraroli, GM and Carretta, A and Ceresoli, G and Calori, G and Zannini, P}, title = {[Treatment of malignant pleural mesothelioma].}, journal = {Minerva chirurgica}, volume = {56}, number = {3}, pages = {243-250}, pmid = {11423790}, issn = {0026-4733}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Mesothelioma/*surgery ; Middle Aged ; Pleural Neoplasms/*surgery ; Retrospective Studies ; }, abstract = {BACKGROUND: In this study all patients observed between January 1993 and October 1997 with malignant pleural mesothelioma (MPM) have been analyzed in order to describe the impact of treatment modality on survival.

METHODS: Medical records of 56 patients with MPM (44 male, 12 female, median age = 59 yrs) were reviewed. In 34 cases the histotype was epithelial, in 4 sarcomatoid, in 4 mixed, in 3 desmoplastic, and in 11 not specified. Four treatment modalities were identified: 1) Surgery (subtotal pleurectomy) = 20 patients; 2) Chemotherapy = 19 patients; 3) Surgery+Chemo-therapy = 8 patients; 4) Supportive care = 9 patients.

RESULTS: The median survival was: 1) Surgery = 12.4 months; 2) Chemotherapy = 7.5 months; 3) Surgery+Chemotherapy = 12 months; 4) Supportive care = 11.4 months. Using univariate analysis, 8 prognostic factors were studied (age, sex, asbestos exposure, side, histotype, performance status, stage, treatment). Among these, only the stage and the performance status had shown a prognostic value on survival (p<0.05), while the treatment modality had not significantly influenced the prognosis. Using multivariate analysis only performance status showed to be significatively associated with survival (p=0.01 and odds ratio = 1.9, I.C. 1.2-3.2).

CONCLUSIONS: Despite the limits of a retrospective study, personal experience confirms the ineffectiveness of current therapeutical approaches to MPM. A better understanding of MPM is required to develop new therapeutical approaches and alter the dismal prognosis of this disease.}, } @article {pmid11417405, year = {2001}, author = {Montanaro, F and Vitto, V and Lagattolla, N and Lazzarotto, A and Bianchelli, M and Puntoni, R and Gennaro, V}, title = {[Occupational exposure to asbestos and recognition of pleural mesothelioma as occupational disease in the province of Genoa].}, journal = {Epidemiologia e prevenzione}, volume = {25}, number = {2}, pages = {71-76}, pmid = {11417405}, issn = {1120-9763}, mesh = {Aged ; Asbestosis/*complications ; Female ; Humans ; Italy ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*epidemiology/etiology ; Workers' Compensation ; }, abstract = {The present study compares the data of pleural mesothelioma (PM) patients resident in the province of Genoa (Italy) who, in the period 1994-1996, applied to the Italian National Insurance Institute for Work Accident (INAIL), for workers' compensation for asbestos-related diseases due to occupational exposure, with the dataset of PM patients collected by the Mesothelioma Registry of Liguria (REM) in the same period and in the same area. As PM is a malignant tumor of a prevalently occupational origin, it is recognized and acknowledged as such by INAIL when clinical and etiological characteristics are matched. Objectives of this study were to describe observed PM cases, to evaluate completeness of collected data and differences between those who requested compensation and those who did not. The REM describes the incidence of PM among Ligurian residents, proposing patients with a specific questionnaire to assess occupational, environmental and indoor asbestos exposures. The REM collected 199 new cases of PM among the residents of both the city of Genoa (1994-96) and the province of Genoa (1995-96). In the same period, INAIL received 48 (24%) applications for compensation. Among these, 43 subjects were included in a subgroup of 98 patients registered in the REM as cases with definite diagnosis and ascertained asbestos exposure; 32 were awarded compensation, while 11 are under evaluation. The data collected by REM do not show proven asbestos exposure and/or PM diagnosis for five other subjects (two compensated and three under judgment). This study reveals that: a) only a 24% of the patients with a diagnosis of PM and asbestos exposure apply for compensation; b) an exchange of information among institutions involved in primary prevention, in the evaluation of occupational exposures to carcinogens and in insurance compensation is useful.}, } @article {pmid11415934, year = {2001}, author = {Metheny-Barlow, LJ and Flynn, B and van Gijssel, HE and Marrogi, A and Gerwin, BI}, title = {Paradoxical effects of platelet-derived growth factor-A overexpression in malignant mesothelioma. Antiproliferative effects in vitro and tumorigenic stimulation in vivo.}, journal = {American journal of respiratory cell and molecular biology}, volume = {24}, number = {6}, pages = {694-702}, doi = {10.1165/ajrcmb.24.6.4334}, pmid = {11415934}, issn = {1044-1549}, mesh = {Animals ; Autocrine Communication ; *Cell Transformation, Neoplastic ; Down-Regulation ; Gene Expression Regulation, Neoplastic ; Humans ; Mesothelioma/*etiology ; Mice ; Mice, Nude ; Paracrine Communication ; Platelet-Derived Growth Factor/*biosynthesis ; Receptor, Platelet-Derived Growth Factor alpha/biosynthesis ; }, abstract = {Malignant mesothelioma is associated with asbestos exposure and remains resistant to all therapeutic intervention. Previous studies have suggested an enhancing role for platelet-derived growth factor (PDGF) in mesothelial tumorigenicity, although the mechanism by which PDGF facilitates tumorigenicity is unknown. Here, we evaluate the contribution of PDGF-A expression to mesothelial tumorigenicity using ectopic modulation of PDGF-A expression. We find, in accordance with other reports, that the receptor for PDGF-A, although expressed at high levels in normal human mesothelial cells, is not easily detectable in mesothelioma. Further, we show that PDGF-A overexpression is responsible for autocrine downregulation of its receptor. Our data indicate, surprisingly, that for mesothelioma cells in vitro, high-level activation of a PDGF-A-PDGF receptor loop is antiproliferative whereas abrogation of PDGF-A expression stimulates growth. These data suggest that PDGF-A does not contribute to tumorigenicity by autocrine stimulation of proliferation. In contrast, increased PDGF-A expression in vivo increases tumor incidence and growth rate and decreases the latency period to tumor formation whereas abrogation of PDGF-A expression decreases tumor incidence and increases latency. Thus, the tumorigenic effect of PDGF-A must act through paracrine mechanisms relevant at early stages of tumor initiation.}, } @article {pmid11414251, year = {2001}, author = {Howie, RM}, title = {Asbestos and cancer risk.}, journal = {The Annals of occupational hygiene}, volume = {45}, number = {4}, pages = {335-6; author reply 336-8}, pmid = {11414251}, issn = {0003-4878}, mesh = {Asbestos/*adverse effects ; Humans ; Lung Neoplasms/etiology/mortality/*prevention & control ; Mesothelioma/etiology/mortality/*prevention & control ; Occupational Exposure/*adverse effects ; Risk Assessment ; }, } @article {pmid11414250, year = {2001}, author = {Liddell, D}, title = {Asbestos and cancer.}, journal = {The Annals of occupational hygiene}, volume = {45}, number = {4}, pages = {329-35; author reply 336-8}, pmid = {11414250}, issn = {0003-4878}, mesh = {Asbestos/*adverse effects ; Humans ; Lung Neoplasms/*etiology/mortality ; Mesothelioma/*etiology/mortality ; Occupational Exposure/*adverse effects ; Regression Analysis ; Risk Assessment ; }, } @article {pmid11414249, year = {2001}, author = {Browne, K}, title = {The quantitative risks of mesothelioma and lung cancer in relation to asbestos exposure.}, journal = {The Annals of occupational hygiene}, volume = {45}, number = {4}, pages = {327-9; author reply 336-8}, pmid = {11414249}, issn = {0003-4878}, mesh = {Asbestos/*adverse effects ; Humans ; Lung Neoplasms/*epidemiology/etiology ; Mesothelioma/*epidemiology/etiology ; Occupational Exposure/*adverse effects ; }, } @article {pmid11409593, year = {2001}, author = {Band, PR and Le, ND and Fang, R and Astrakianakis, G and Bert, J and Keefe, A and Krewski, D}, title = {Cohort cancer incidence among pulp and paper mill workers in British Columbia.}, journal = {Scandinavian journal of work, environment & health}, volume = {27}, number = {2}, pages = {113-119}, doi = {10.5271/sjweh.597}, pmid = {11409593}, issn = {0355-3140}, mesh = {British Columbia/epidemiology ; Cohort Studies ; Humans ; Incidence ; Male ; Neoplasms/*epidemiology/etiology ; Occupational Diseases/*epidemiology/etiology ; Paper ; Risk Factors ; }, abstract = {OBJECTIVES: A study was conducted to investigate cancer risks in a cohort of pulp and paper workers.

METHODS: All male workers with > or =1 years of employment in 14 pulp and paper mills in 1950-1992 were studied. Standardized incidence ratios (SIR) were used to compare the cancer incidence of the cohort with that of the Canadian male population. Record linkage with the National Cancer Registry was performed using the generalized iterative record linkage method.

RESULTS: Altogether 1756 cancer cases were observed in the entire cohort. For > or =15 years of work, the entire cohort had significantly increased SIR values for pleural and prostate cancer and skin melanoma; there was also a significantly increased risk for skin melanoma among workers in the kraft process only, rectal cancer among workers in the sulfite process only, and stomach and prostate cancer and all leukemias combined among workers in both the kraft and sulfite processes. A separate analysis comparing workers in pulping and papermaking with those in the pulping process only did not reveal any difference in cancer risk and hence did not modify the results. The SIR values for skin melanoma were not significantly increased in a comparison using the British Columbia male population. Nine of 10 pleural cancers were mesotheliomas, which likely reflect past asbestos exposure.

CONCLUSIONS: The results suggest that long-term work in the pulp and paper industry is associated with excess risks of prostate and stomach cancers and all leukemias for work in both kraft and sulfite processes and of rectal cancer for work in the sulfite process only.}, } @article {pmid11408072, year = {2001}, author = {Ascoli, V and Aalto, Y and Carnovale-Scalzo, C and Nardi, F and Falzetti, D and Mecucci, C and Knuutila, S}, title = {DNA copy number changes in familial malignant mesothelioma.}, journal = {Cancer genetics and cytogenetics}, volume = {127}, number = {1}, pages = {80-82}, doi = {10.1016/s0165-4608(00)00420-9}, pmid = {11408072}, issn = {0165-4608}, mesh = {Aged ; Chromosome Aberrations/*genetics ; DNA, Neoplasm/*analysis ; Female ; *Gene Dosage ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Male ; Mesothelioma/*genetics/pathology ; Middle Aged ; Nucleic Acid Hybridization ; Pedigree ; Pleural Neoplasms/*genetics/pathology ; Sequence Deletion ; }, abstract = {Malignant mesothelioma (MM) is predominantly a sporadic malignancy linked to exposure to asbestos. Clustering of MM in families suggests genetic susceptibility as a contributing factor. We performed comparative genomic hybridization (CGH) analysis on tumor samples from members of a family with MM of the pleura and a history of parental cancer. Our specific aim was to find a recurrent copy number loss indicating the chromosomal area to which a gene underlying the development of MM could be assigned according to the Knudson two-hit hypothesis. We found losses at 1p, 6q, 9p, 13q, and 14q. The copy number changes were very similar to those reported in sporadic cases. Our findings and results from sporadic cases highlight the importance of cloning the genes in the loss sites at 1p, 6q, 14q, and 22q.}, } @article {pmid11386181, year = {2001}, author = {Colli, G and Terzi, M and Vinci, L and Terzi, R and Candura, SM}, title = {[A case of pleural mesothelioma caused by unusual occupational exposure to asbestos in the wool industry].}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {23}, number = {1}, pages = {18-20}, pmid = {11386181}, issn = {1592-7830}, mesh = {Aged ; Animals ; Asbestosis/*etiology ; Humans ; Male ; Mesothelioma/*etiology ; *Occupational Exposure ; Pleural Neoplasms/*etiology ; *Wool ; }, abstract = {We report the case of a 73-year-old worker who died of pleural mesothelioma, after being employed for 35 years in a wool textile plant of Biella (Italy). Close investigations revealed that he provided for the maintenance of materials and machines. In particular, he used to replace asbestos parts such as rings, joints and insulations of pipelines (dyeing unit), as well as brake linings of warping, looming and combing machines. Beside confirming the importance of an accurate occupational anamnesis to recognize work-induced cancers, the case draws the attention on the risk of mesothelioma in the wool industry, an occupational setting that is not usually considered as a potential source of exposure to asbestos fibres. Such pollution might explain the increased mortality due to pleural mesothelioma in the Biella area (characterized by a prosperous textile industry), reported in previous epidemiological studies.}, } @article {pmid11379480, year = {2000}, author = {Bianchi, C and Brollo, A and Ramani, L and Bianchi, T}, title = {Malignant mesothelioma in central and Eastern Europe.}, journal = {Acta medica Croatica : casopis Hravatske akademije medicinskih znanosti}, volume = {54}, number = {4-5}, pages = {161-164}, pmid = {11379480}, issn = {1330-0164}, mesh = {Asbestos/adverse effects ; Europe, Eastern/epidemiology ; Humans ; Incidence ; Lung Neoplasms/epidemiology/etiology ; Mesothelioma/*epidemiology/etiology ; Occupational Diseases/epidemiology/etiology ; Occupational Exposure ; Pleural Neoplasms/*epidemiology/etiology ; }, abstract = {To obtain data on mesothelioma incidence in Central and Eastern Europe, a short questionnaire was sent to 83 researchers from 19 countries. The questions referred to the approximate number of mesotheliomas diagnosed per year in the country, degree of asbestos consumption, and percentage of lung carcinomas attributable to asbestos. Answers were received from 12 countries. For some major asbestos producers and/or consumers, such as Russia and Ukraine, mesothelioma data were unavailable or unreliable. In various countries of Central-Eastern Europe, the crude incidence of mesothelioma appeared to be lower than in Western countries. The reported annual numbers of mesotheliomas were 120 in Poland, 133 in Romania, and 78 in Hungary. Among the countries with a population of 5 million or less, the highest incidence was observed in Croatia (46 cases per year, peritoneal tumors not included). Data on the percentage of asbestos-related lung carcinomas are lacking. The knowledge about asbestos related cancer in Central and Eastern Europe remains fragmentary. Further investigations in this relevant area of public health should be encouraged.}, } @article {pmid11344752, year = {2000}, author = {Ariad, S and Barchana, M and Yukelson, A and Geffen, DB}, title = {A worrying increase in the incidence of mesothelioma in Israel.}, journal = {The Israel Medical Association journal : IMAJ}, volume = {2}, number = {11}, pages = {828-832}, pmid = {11344752}, issn = {1565-1088}, mesh = {Adult ; Age Distribution ; Aged ; Asbestosis/diagnosis/*epidemiology ; Comorbidity ; Female ; Health Surveys ; Humans ; Incidence ; Israel/epidemiology ; Lung Neoplasms/diagnosis/*epidemiology ; Male ; Mesothelioma/diagnosis/*epidemiology ; Middle Aged ; Registries ; Risk Factors ; Sex Distribution ; Time Factors ; }, abstract = {BACKGROUND: Exposure to asbestos is the main established cause of mesothelioma; the incidence of this tumor is thus often interpreted as an index of past exposure. Asbestos has been widely used in Israel in industry and building, exposing certain population groups to the risk of developing mesothelioma.

OBJECTIVES: To analyze the incidence of mesothelioma in Israel during the years 1960-96, and to project its trend for the following years.

METHODS: We conducted a population-based study of the incidence of mesothelioma reported to the Israel Cancer Registry during 1960-96. Time trends were analyzed from data on the annual import of asbestos to Israel, which may indicate the magnitude of past exposure. Based on these findings, trends in the incidence of mesothelioma in Israel were projected for the subsequent years.

RESULTS: A total of 327 cases of mesothelioma were reported to the Israel Cancer Registry during the study period. The incidence in Jews was higher than in Arabs (age-standardized incidence rate 2.64 vs. 1.35 per million/year, respectively). Among the Jewish population, Israeli-born males and males born in Europe and America showed the highest incidence (ASR 4.23 and 4.15 per million/year, respectively). Israeli-born males were 20 years younger than Jewish males born elsewhere. The incidence was twice as high among males than females and increased sevenfold from its nadir (1.17 per million/year) in 1978-80 to its peak (8.5 per million/year) in 1993-96. During a similar period the incidence among females increased from 0.33 to 2.56 per million/year. The incidence in both sexes does not appear to level off. The large wave of immigration from the former Soviet Union that began in 1989 only partly accounts for the increased incidence in 1993-96. The time trend in the incidence of mesothelioma in both sexes parallels the use of asbestos in Israel, which peaked in the years 1976-78.

CONCLUSIONS: The incidence of mesothelioma in Israel has increased sharply in recent years, unrelated to a wave of immigration from East Europe, and is predicted to continue to rise for another 10-15 years.}, } @article {pmid11341561, year = {2001}, author = {Cai, SX and Zhang, CH and Zhang, X and Morinaga, K}, title = {Epidemiology of occupational asbestos-related diseases in China.}, journal = {Industrial health}, volume = {39}, number = {2}, pages = {75-83}, doi = {10.2486/indhealth.39.75}, pmid = {11341561}, issn = {0019-8366}, mesh = {Asbestos/*adverse effects ; Asbestosis/*epidemiology ; China/epidemiology ; Humans ; Lung Neoplasms/*epidemiology/*etiology ; Mesothelioma/*epidemiology/*etiology ; *Occupational Exposure ; Prevalence ; Risk ; }, abstract = {In 1950s and 60s, asbestosis had been a major health hazard for asbestos exposed workers. In the late 1970s, lung cancers with or without asbestosis were found among asbestos workers. All cohort studies on asbestos workers and on chrysotile miners in China showed excess deaths from lung cancer. In a large scale of cohort study on asbestos workers, a synergistic effect was found between cigarette smoking and asbestos exposure in the production of lung cancer. There have been not so many cases of malignant mesotheliomas reported, so far. In the cohort of chrysotile miners, 4 cases of pleural mesothelioma were observed. In the large scale of cohort study on asbestos workers in 9 factories using only chrysotile only one case of pleural mesothelioma was detected for 10 years' observation. In another 2 cohort studies, 2 cases of peritoneal mesotheliomas were found, one in Shanghai asbestos factory where a small amount of crocidolite had been used in 1960s, and one in Anqing asbestos factory that was located near tremolite mine. Further study is needed especially for the relationship between exposure to Chinese chrysotile and malignant mesotheliomas.}, } @article {pmid11341560, year = {2001}, author = {Morinaga, K and Kishimoto, T and Sakatani, M and Akira, M and Yokoyama, K and Sera, Y}, title = {Asbestos-related lung cancer and mesothelioma in Japan.}, journal = {Industrial health}, volume = {39}, number = {2}, pages = {65-74}, doi = {10.2486/indhealth.39.65}, pmid = {11341560}, issn = {0019-8366}, mesh = {Asbestos/*adverse effects ; Humans ; Japan/epidemiology ; Lung Neoplasms/*epidemiology/*etiology ; Mesothelioma/*epidemiology/*etiology ; Occupational Exposure ; Smoking/adverse effects/epidemiology ; }, abstract = {In Japan, crocidolite had been used for asbestos cement pipe and spraying, and amosite had been used for building board and spraying. These two types of asbestos had stopped to use in Japan in the late 1970s. An extreme increase in imported asbestos (all 3 commercial types) was observed between 1960 and 1974. In 1960, 77,000 tons of asbestos were imported, and reached the peak as 352,316 tons in 1974. This extreme rise of asbestos imports corresponds with the recent rapid increase in mortality of malignant pleural mesothelioma. Between 1995 and 1999, an estimated mean annual death from pleural mesothelioma was about 500. The annual number of compensated occupational respiratory cancers due to asbestos exposure has also been increasing. Up to the end of March 2000, 162 cases with malignant mesothelioma and 197 cases with lung cancer were compensated. As for lung cancer, epidemiological studies are scanty in Japan. Limited environmental data of the working places in asbestos textile factories suggests that heavy asbestos exposure in the past made deaths from respiratory diseases. Less asbestos exposure will enable exposed workers to survive enough to reach cancer age. Even now smoking rate among males in Japan are over 50%. So lung cancer deaths caused by the interaction between smoking and asbestos exposure will be continuing.}, } @article {pmid11341559, year = {2001}, author = {Nicholson, WJ}, title = {The carcinogenicity of chrysotile asbestos--a review.}, journal = {Industrial health}, volume = {39}, number = {2}, pages = {57-64}, doi = {10.2486/indhealth.39.57}, pmid = {11341559}, issn = {0019-8366}, mesh = {Asbestos, Serpentine/*adverse effects ; Carcinogens/*adverse effects ; Humans ; Lung Neoplasms/epidemiology/*etiology ; Mesothelioma/epidemiology/*etiology ; Occupational Exposure ; Risk ; }, abstract = {The world production of asbestos has been declining dramatically in recent years, particularly in Europe and the United States. However, increases have occurred in Asian nations and chrysotile is the dominant fiber used. Important uses are in cement products, wallboards, friction products and textiles. From studies in the United States and Great Britain, chrysotile has been shown to increase the risk of lung cancer and to produce mesothelioma in exposed workers.}, } @article {pmid11341549, year = {2001}, author = {Suzuki, Y}, title = {Pathology of human malignant mesothelioma--preliminary analysis of 1,517 mesothelioma cases.}, journal = {Industrial health}, volume = {39}, number = {2}, pages = {183-185}, doi = {10.2486/indhealth.39.183}, pmid = {11341549}, issn = {0019-8366}, mesh = {Adult ; Aged ; Aged, 80 and over ; Autopsy ; Biopsy ; Female ; Humans ; Male ; Mesothelioma/*pathology ; Middle Aged ; Occupational Exposure ; Peritoneal Neoplasms/pathology ; Pleural Neoplasms/pathology ; United States ; }, abstract = {The author reviewed 1,517 human malignant mesothelioma cases from 1975 through August 2000. These mesothelioma cases were definite or probable in diagnostic certainty. Sources of these cases varied including asbestos insulation workers, UNARCO workers, Cancer and Leukemia B mesothelioma panel cases and random cases. Pathology materials consisted of autopsy, biopsy and rare cytology specimens. 92.3% of these patients were male, and 85.8% were between 50 and 79 years in age. The major primary site of the tumor was the pleura (73.1%). However, in a group of the asbestos insulation workers, the peritoneum was the more common primary site of malignant mesothelioma, compared to the pleura. Histologically, epithelial cell type was the majority (61.1%), followed by biphasic (22.1%) and fibrosarcomatous (16.4%). A double primary tumor (malignant mesothelioma associated with other cancer) was present in 32 of the 1,517 cases. These 32 cancers included lung cancers, renal cell carcinomas, colorectal cancers, pancreatic cancers and a cancer of the larynx, which are known to be at higher risk among asbestos insulation workers. The latency period of the vast majority (98.1%) of these mesothelioma cases were longer than 20 years. It is well accepted that cigarette smoking does not contribute to the induction of malignant mesothelioma. Indeed, the present study confirmed that 19.9% of these mesothelioma patients had never smoked cigarettes.}, } @article {pmid11341547, year = {2001}, author = {Adachi, S and Kawamura, K and Takemoto, K}, title = {A trial on the quantitative risk assessment of man-made mineral fibers by the rat intraperitoneal administration assay using the JFM standard fibrous samples.}, journal = {Industrial health}, volume = {39}, number = {2}, pages = {168-174}, doi = {10.2486/indhealth.39.168}, pmid = {11341547}, issn = {0019-8366}, mesh = {Animals ; Carcinogens/toxicity ; Female ; Injections, Intraperitoneal ; Mesothelioma/*etiology/pathology ; Mineral Fibers/*toxicity ; Peritoneal Neoplasms/*etiology/pathology ; Rats ; Rats, Inbred F344 ; Risk Assessment ; }, abstract = {We tried to evaluate the carcinogenic risk of man-made mineral fiber based on the mesothelioma incidence in female F344 rats after intraperitoneal administration. Rats (female F344/ Nslc, 5-week-old, n=330) were observed for 2 years after the intraperitoneal administration of 5 to 20 mg of 9 types of the JFM (Japan Fibrous Material Research Association) standard fiber samples (glass wool, rock wool, micro fiber glass, three types of refractory fiber, potassium titanate whisker, silicon carbide whisker, titanium oxide whisker), wollastonite (natural fiber) and UICC chrysotile B. All rats administered 10 mg of silicon carbide whisker had developed peritoneal mesothelioma within a year. The cumulative incidence of peritoneal mesothelioma at the end of the experiment was 85% for 10 mg UICC chrysotile B, 77% for 10 mg of potassium titanate whisker, 70% for 5 mg of silicon carbide whisker, 20% for 5 mg of potassium titanate whisker, 20% for 20 mg of refractory fiber 2 and 10% for 20 mg of refractory fiber 1. Carcinogenicity was estimated 2.4 times for silicon carbide whisker and 0.23 for potassium titanate whisker in comparison with UICC chrysotile B. It has been well documented from several experimental studies that man-made fibers are safer than asbestos because of the different durability in the lung. Present results consistently suggest that man-made fibers with high durability have similar or higher risk as carcinogen than asbestos.}, } @article {pmid11341546, year = {2001}, author = {Bianchi, C and Brollo, A and Ramani, L and Bianchi, T and Giarelli, L}, title = {Asbestos exposure in malignant mesothelioma of the pleura: a survey of 557 cases.}, journal = {Industrial health}, volume = {39}, number = {2}, pages = {161-167}, doi = {10.2486/indhealth.39.161}, pmid = {11341546}, issn = {0019-8366}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects/*analysis ; Body Burden ; Female ; Humans ; Italy/epidemiology ; Lung Neoplasms/*epidemiology/*etiology ; Male ; Mesothelioma/*epidemiology/*etiology ; Middle Aged ; Occupational Exposure/*adverse effects ; Occupations ; }, abstract = {A series of 557 malignant mesotheliomas of the pleura diagnosed in the Trieste-Monfalcone area, Italy, in the period 1968-2000 were reviewed. The series included 492 men and 65 women, aged between 32 and 93 years (median age 69 years). Necropsy findings were available in 456 cases (82%). Occupational histories were obtained from the patients themselves or from their relatives by personal or telephone interviews. Routine lung sections were examined for asbestos bodies in 442 cases. In 109 cases isolation and counting of asbestos bodies were performed. A majority of people had histories of working in the shipyards. Asbestos bodies were observed in lung sections in 67% of the cases. Lung asbestos body burdens after isolation ranged between 20 bodies and about 10 millions of bodies/g dried tissue. Latency periods (time intervals between first exposure to asbestos and death) ranged between 14 and 75 years (mean 48.8 years, median 51.0). Latency periods among insulators and dock workers were shorter than among the other categories. High asbestos consumption occurred in many countries in the 1960s and in the 1970s. The data on latency periods obtained in the present study suggest that a world mesothelioma epidemic has to be expected in the coming decades.}, } @article {pmid11341545, year = {2001}, author = {Suzuki, Y and Yuen, SR}, title = {Asbestos tissue burden study on human malignant mesothelioma.}, journal = {Industrial health}, volume = {39}, number = {2}, pages = {150-160}, doi = {10.2486/indhealth.39.150}, pmid = {11341545}, issn = {0019-8366}, mesh = {Asbestos/*adverse effects/*analysis ; Female ; Humans ; Lung Neoplasms/*etiology ; Male ; Mesothelioma/*etiology ; Microscopy, Electron ; Mineral Fibers/adverse effects/analysis ; Occupational Exposure/*adverse effects ; Occupations ; }, abstract = {Asbestos fibers in the lung and mesothelial tissues (mesotheliomatous tissue and hyaline plaque) taken from 151 human malignant mesothelioma cases were identified and characterized by high resolution analytical electron microscopy. Asbestos fibers were present in almost all of the lung tissue as well as in the mesothelial tissue. The most common asbestos types seen in the lung were an admixture of chrysotile with amphiboles followed by amphiboles alone and chrysotile alone. The majority of asbestos types seen in the mesothelial tissues were chrysotile alone, followed by chrysotile plus amphibole and amphibole alone. A disproportion of asbestos types between the lung and mesothelial tissues was frequently observed. The most common pattern of the disproportion was chrysotile plus amphibole(s) in the lung and chrysotile only in the mesothelial tissues, followed by amphibole(s) in the lung and chrysotile only in the mesothelial tissues. Such a disproportion was considered to have been caused by chrysotile fiber's strong capacity to translocate from the lung to mesothelial tissues. The number of asbestos fibers in the lung was 456.4 x 10(6) fibers/dry gram in maximum, 0.08 x 106 fibers/dry gram in minimum and 105 x 10(6) fibers/dry gram on average; in the mesothelial tissues it was 240.0 x 106 fibers/dry gram in maximum, 0.03 x 106 fibers/dry gram in minimum and 49.84 x 106 fibers/dry gram on average. These numbers were greater than those seen in the general population. The majority of asbestos fibers detected in the lung and mesothelial tissues were shorter than 5 microm in length. Asbestos fibers fit to Stanton's hypothetical dimensions (> or =8.0 microm in length and < or =0.25 microm in diameter) were only 4.0%, since the majority of these fibers were shorter (<8 microm) and thinner (<0.25 microm) fibers. We concluded that such short, thin asbestos fibers should not be excluded from those contributing to the induction of human malignant mesothelioma. The present study supports that chrysotile asbestos can induce human malignant mesothelioma, since, in some of the mesothelioma cases, asbestos fibers detected in both the lung and mesothelial tissues, or lung tissue alone or mesothelial tissues alone were exclusively chrysotile fibers.}, } @article {pmid11338024, year = {2001}, author = {Jaklitsch, MT and Grondin, SC and Sugarbaker, DJ}, title = {Treatment of malignant mesothelioma.}, journal = {World journal of surgery}, volume = {25}, number = {2}, pages = {210-217}, doi = {10.1007/s002680020021}, pmid = {11338024}, issn = {0364-2313}, mesh = {Combined Modality Therapy ; Genetic Therapy ; Humans ; Immunotherapy ; Mesothelioma/mortality/surgery/*therapy ; Patient Selection ; Photochemotherapy ; Pleural Neoplasms/mortality/surgery/*therapy ; Pneumonectomy ; Quality of Life ; Radiotherapy Dosage ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare tumor that predominantly afflicts men over 50 years of age. Nearly 3000 MPMs are reported annually in the United States with the incidence expected to rise into the new millenium. Over the past 40 years, MPM has been unequivocally linked to asbestos exposure worldwide. Recently, however, a new theory on the carcinogenesis of this tumor has been proposed with the isolation of a simian virus (SV 40)-like gene sequence in mesothelioma tumor cells. The clinical presentation of MPM is variable, although most patients typically present with dyspnea, chest pain, or pleural effusion. Obtaining a diagnosis of MPM has been greatly assisted by video-assisted surgery and the use of immunohistochemistry and electron microscopic techniques, which help distinguish MPM from other tumor pathologies such as adenocarcinoma. Computed tomography and magnetic resonance imaging have been also useful for determining tumor burden and resectability. Traditionally, strategies for the treatment of MPM have included supportive care, surgery, radiotherapy, and chemotherapy. Survival with supportive care alone ranges between 4 and 12 months. Single-modality therapy using traditional approaches (surgery, radiotherapy, chemotherapy) alone has failed to improve patient survival significantly. Recently, results using a multimodality approach have been favorable. In particular, cytoreductive surgery (pleuropneumonectomy) followed by sequential chemotherapy and radiotherapy have demonstrated improved survival, especially for patients with epithelial histology, negative resection margins, and no metastases to extrapleural lymph nodes. Innovative therapies such as the use of photodynamic, targeted cytokines and gene therapy are currently being investigated for management of MPM.}, } @article {pmid11333419, year = {2001}, author = {Ludwig, ER and Madeksho, L and Egilman, D}, title = {RE: Mesothelioma and lung tumors attributable to asbestos among petroleum workers. Am. J. Ind. Med. 2000. 37:275-282.}, journal = {American journal of industrial medicine}, volume = {39}, number = {5}, pages = {524-527}, doi = {10.1002/ajim.1051}, pmid = {11333419}, issn = {0271-3586}, mesh = {Asbestos/*adverse effects ; Humans ; Italy/epidemiology ; Lung Neoplasms/*chemically induced/epidemiology ; Mesothelioma/*chemically induced/epidemiology ; Occupational Diseases/*chemically induced/epidemiology ; *Occupational Exposure ; Petroleum/*adverse effects ; }, } @article {pmid11333416, year = {2001}, author = {Tsai, SP and Waddell, LC and Ransdell, JC}, title = {RE: Mesothelioma and lung tumors attributable to asbestos among petroleum workers. Am. J. Ind. Med. 2000. 37:275-282.}, journal = {American journal of industrial medicine}, volume = {39}, number = {5}, pages = {515-21; author reply 517-21}, doi = {10.1002/ajim.1048}, pmid = {11333416}, issn = {0271-3586}, mesh = {Asbestos/*adverse effects ; Humans ; Lung Neoplasms/*chemically induced/epidemiology ; Mesothelioma/*chemically induced/epidemiology ; Occupational Diseases/*chemically induced/epidemiology ; *Occupational Exposure ; Petroleum/*adverse effects ; }, } @article {pmid11333415, year = {2001}, author = {Bailey, WJ}, title = {RE: Mesothelioma and lung tumors attributable to asbestos among petroleum workers. Am. J. Ind. Med. 2000. 37:275-282.}, journal = {American journal of industrial medicine}, volume = {39}, number = {5}, pages = {513-4, 522-3; author reply 517-21}, doi = {10.1002/ajim.1047}, pmid = {11333415}, issn = {0271-3586}, mesh = {Asbestos/*adverse effects ; Humans ; Italy/epidemiology ; Lung Neoplasms/*chemically induced/epidemiology ; Mesothelioma/*chemically induced/epidemiology ; Occupational Diseases/*chemically induced/epidemiology ; *Occupational Exposure ; Petroleum/*adverse effects ; }, } @article {pmid11325497, year = {2001}, author = {van Hengel, P and van Geffen, F and Kazzaz, BA and Heyerman, HG}, title = {Atypical carcinoid presenting as mesothelioma.}, journal = {The Netherlands journal of medicine}, volume = {58}, number = {4}, pages = {185-190}, doi = {10.1016/s0300-2977(01)00089-4}, pmid = {11325497}, issn = {0300-2977}, mesh = {Aged ; Asbestosis/diagnosis ; Autopsy ; Carcinoid Tumor/*diagnosis ; Diagnosis, Differential ; Fatal Outcome ; Humans ; Lung Neoplasms/*diagnosis ; Male ; Mesothelioma/*diagnosis ; }, abstract = {Two patients presented with pleuritic pain and dyspnoe together with pleural thickening on the X-ray of the chest. In both a history of exposure to asbestos existed suggesting mesothelioma. A definite diagnosis could not be made and therefore therapy was symptomatic. Autopsy revealed the unexpected diagnosis of atypical carcinoid of the lung. In one case, pleural spread of tumor was seen while in the other an extensive fibrotic pleural reaction existed. To our knowledge these cases represent the first examples of atypical carcinoid causing pseudomesothelioma.}, } @article {pmid11325491, year = {2001}, author = {Robinson, BW and Robinson, C and Lake, RA}, title = {Localised spontaneous regression in mesothelioma -- possible immunological mechanism.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {32}, number = {2}, pages = {197-201}, doi = {10.1016/s0169-5002(00)00217-8}, pmid = {11325491}, issn = {0169-5002}, mesh = {Antibodies, Neoplasm/*blood ; Antigens, Neoplasm/*immunology ; Asbestos, Crocidolite/adverse effects ; Disease Progression ; Fatal Outcome ; Female ; Follow-Up Studies ; Humans ; Lung/chemistry ; Lymphocytes, Tumor-Infiltrating ; Mesothelioma/diagnostic imaging/etiology/*immunology/pathology ; Middle Aged ; Mineral Fibers/analysis ; Neoplasm Regression, Spontaneous/*immunology ; Occupational Diseases/etiology/immunology/pathology ; Pleural Neoplasms/diagnostic imaging/etiology/*immunology/pathology ; Tomography, X-Ray Computed ; Tumor Cells, Cultured/immunology ; }, abstract = {Malignant mesothelioma (MM) is an aggressive tumor usually associated with asbestos exposure. Although it can remain stable for prolonged periods, it has not been described to spontaneously regress. MM tumors are thought to be immunogenic based both on animal studies and on the good responses in some humans treated with immunotherapy. Here we present a case of pleural MM in which a transient spontaneous regression was associated with tumor tissue infiltration with mononuclear cells and serological evidence of anti-MM reactivity. The patient's tumor eventually progressed and with this progression there was evidence of loss of serological reactivity to some, but not all, of her MM antigens. The patient survived for 20 months and, in contrast to her initial biopsy, no significant lymphoid infiltrate was detected in her MM tissue at post mortem examination.}, } @article {pmid11323795, year = {2001}, author = {Merler, E and Silvestri, S and Mauro, L and Campinoti, G}, title = {Re: mortality among workers in the geothermal power plants at Larderello, Italy. Am. J. Ind. Med. 35:536-539, 2000.}, journal = {American journal of industrial medicine}, volume = {39}, number = {4}, pages = {436-7; author reply 438}, doi = {10.1002/ajim.1036}, pmid = {11323795}, issn = {0271-3586}, mesh = {Asbestos/*adverse effects ; Cohort Studies ; Humans ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology/mortality ; Neoplasms/mortality ; Occupational Diseases/*mortality ; Occupational Exposure ; *Power Plants ; }, } @article {pmid11320279, year = {2001}, author = {Farmer, CK and Goldsmith, DJ}, title = {Nephrotic syndrome and mesenteric infarction secondary to metastatic mesothelioma.}, journal = {Postgraduate medical journal}, volume = {77}, number = {907}, pages = {333-334}, doi = {10.1136/pmj.77.907.333}, pmid = {11320279}, issn = {0032-5473}, mesh = {Aged ; Fatal Outcome ; Humans ; Lung Neoplasms/*complications/pathology ; Male ; Mesenteric Vascular Occlusion/*etiology/pathology ; Mesothelioma/*complications/pathology/secondary ; Nephrotic Syndrome/*etiology/pathology ; }, abstract = {Malignant mesothelioma can present insidiously with progressive breathlessness and chest pain. Paraneoplastic, or non-chest related, presentations are very rare. The case of an elderly man with occupational exposure to asbestos who presented with nephrotic syndrome due to minimal change nephropathy in the context of advanced pleural mesothelial malignancy is reported.}, } @article {pmid11317707, year = {2001}, author = {Rödelsperger, K and Mándi, A and Tossavainen, A and Brückel, B and Barbisan, P and Woitowitz, HJ}, title = {Inorganic fibres in the lung tissue of Hungarian and German lung cancer patients.}, journal = {International archives of occupational and environmental health}, volume = {74}, number = {2}, pages = {133-138}, doi = {10.1007/s004200000202}, pmid = {11317707}, issn = {0340-0131}, mesh = {Adult ; Aged ; Asbestos/*adverse effects/analysis ; Asbestos, Amphibole/adverse effects/analysis ; Asbestos, Serpentine/adverse effects/analysis ; Case-Control Studies ; Female ; Germany/epidemiology ; Humans ; Hungary/epidemiology ; Logistic Models ; Lung/*pathology ; Lung Neoplasms/*etiology/*pathology ; Male ; Microscopy, Electron, Scanning Transmission ; Middle Aged ; Mineral Fibers/adverse effects/analysis ; Occupational Exposure/*adverse effects/analysis ; Occupations ; Statistics, Nonparametric ; }, abstract = {OBJECTIVE: To ascertain the lung burden of asbestos fibres in Hungarian lung cancer patients in comparison with the cumulative asbestos exposure estimated from the occupational history.

METHODS: For 25 Hungarian lung cancer patients, lung tissue fibre analysis was performed by scanning transmission electron microscopy (STEM) and counting of ferruginous bodies (FBs) by light microscopy. Cumulative asbestos exposure in fibre-years was assessed from a standardised occupational history using the report "fibre years" of the German Berufsgenossenschaften.

RESULTS: Median and maximum concentrations of fibres longer 5 microns per gram dry lung tissue (g dry) were 0.03 and 7.38 million fibres/g dry for chrysotile, 0.00 and 0.21 million fibres/g dry for amphibole and 0.22 and 0.62 million fibres/g dry for other mineral fibres (OMFs). The maximum values were observed in one patient for whom a high asbestos exposure was evident in advance from the occupational history.

CONCLUSIONS: In comparison with reference values obtained by the same method for German patients with no indication of workplace asbestos exposure, increased concentrations of more than 0.2 million chrysotile fibres/g dry were obtained for six of the 25 Hungarian patients (24%). For one of them, the second highest estimate of a workplace exposure of 60 fibre-years and the highest tissue concentration of 7.38 million chrysotile fibres/g dry substantiate a high probability of a causal relationship to asbestos. A further comparison can be made with the results for 66 German patients treated by surgical lung resection for a disorder other than mesothelioma, mainly lung cancer. For the Hungarian lung cancer patients, similar amounts of chrysotile but distinctly lower amounts of amphibole fibres and distinctly higher amounts of OMFs were observed. A correlation between exposure estimates from occupational history and concentration of fibres in the lung tissue was observed for amphibole (Spearman: R = 0.66, P < 0.001, Pearson: R = 0.50, P = 0.01) and for chrysotile (Pearson: R = 0.48, P = 0.02).}, } @article {pmid11313208, year = {2001}, author = {Mohr, S and Rihn, B}, title = {[Gene expression profiling in human mesothelioma cells using DNA microarray and high-density filter array technologies].}, journal = {Bulletin du cancer}, volume = {88}, number = {3}, pages = {305-313}, pmid = {11313208}, issn = {0007-4551}, mesh = {Cell Adhesion ; Cell Division ; Cell Line ; Cell Transformation, Neoplastic/*genetics ; Drug Resistance, Neoplasm ; *Gene Expression Profiling ; Humans ; Mesothelioma/*genetics ; Neoplasm Invasiveness ; Oligonucleotide Array Sequence Analysis ; Pleural Neoplasms/*genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Tumor Cells, Cultured ; }, abstract = {Although the use of asbestos has been banned in most industrialized countries, it is still a major public health concern. Asbestos fibers are mutagenic and carcinogenic for humans, classified as "carcinogen category 1 (T, R45: can cause the cancer)" in the 25th adaptation of the directive 67/548/EEC. In France, asbestos is thought to be responsible each year for many pulmonary diseases: pleural plaque, bronchogenic carcinoma and mesothelioma (malignant tumor of pleura). In order to better understand the transformation process of pleural cells, we compared the gene expression of mesothelium cells (Met-5A) and mesothelioma cells (MSTO-211H) using high-density filter array (588 genes) and microarray (6.969 genes). Results of both technologies were compared and expression levels of several genes were confirmed by quantitative RT-PCR. Data analysis with GemtoolsTM 2.4 software allows us hierarchical classification of genes of known functions by enzyme, function and pathway clusters and leads to characterize both malignant and normal phenotypes. Finally, the comparison between the two cell lines provides new markers of mesothelioma and pleura. They could be useful for diagnostic, prognostic and therapeutic.}, } @article {pmid11303081, year = {2001}, author = {Andersson, E and Hagberg, S and Nilsson, T and Persson, B and Wingren, G and Torén, K}, title = {A case-referent study of cancer mortality among sulfate mill workers in Sweden.}, journal = {Occupational and environmental medicine}, volume = {58}, number = {5}, pages = {321-324}, pmid = {11303081}, issn = {1351-0711}, mesh = {Adult ; Aged ; Case-Control Studies ; Humans ; Industry ; Male ; Middle Aged ; Neoplasms/chemically induced/*mortality ; Occupational Exposure/*adverse effects ; Odds Ratio ; Risk Factors ; Sulfates/*adverse effects ; Sweden/epidemiology ; }, abstract = {OBJECTIVES: To investigate whether workers in Swedish sulfate mills have an increased risk of death from certain malignancies that have previously been linked to the pulping process.

METHODS: Subjects of the study (n=2480) were men aged 40-75 at death during 1960-89 in the parishes surrounding four sulfate mills. Exposure assessment was based on information from the personnel files in the mills- 35% of the subjects were recognised there, and work categories were created.

RESULTS: Among all sulfate mill workers, the odds ratio (OR) (90% confidence interval (90% CI)) for death from lung cancer was 1.6 (1.1 to 2.3), pleural mesotheliomas 9.5 (1.9 to 48), brain tumours 2.6 (1.2 to 5.3), and liver or biliary tract cancer 2.3 (1.0 to 5.2). There was an increased mortality from leukaemia among workers in the soda recovery plant (5.9 (2.6 to 13)) and bleaching plant and digester house (2.8 (1.0 to 7.5)).

CONCLUSIONS: Sulfate mill workers were at increased risk of dying from lung cancer and pleural mesotheliomas, probably due to exposure to asbestos. Increased risks of brain tumours and cancers of the liver or biliary tract were also found but the aetiology is not obvious.}, } @article {pmid11302347, year = {2001}, author = {Bandoh, S and Fujita, J and Fukunaga, Y and Ohtsuka, S and Susaki, K and Yang, Y and Kobayashi, S and Takahara, J}, title = {Nodular thickening of interlobar fissures: an early manifestation of malignant mesothelioma: a case report.}, journal = {Japanese journal of clinical oncology}, volume = {31}, number = {2}, pages = {82-85}, doi = {10.1093/jjco/hye016}, pmid = {11302347}, issn = {0368-2811}, mesh = {Asbestosis/*complications/*pathology ; Diagnosis, Differential ; Humans ; Male ; Mesothelioma/*diagnosis/pathology ; Middle Aged ; Pleural Neoplasms/*diagnosis/pathology ; Tomography, X-Ray Computed ; }, abstract = {Two men with occupational exposure to asbestos were admitted to our hospital with minute pleural changes on their chest CT image. Conventional computed tomography (CT) scans of the chest showed slightly thickened interlobar fissures and a small amount of pleural effusion. In addition, high-resolution CT showed small nodular opacities on interlobar fissures. There were no intrapulmonary mass shadows, pleural plaques or other extrapulmonary mass shadows. These roentgenographical findings were very similar to each other. Hyarulonic acid values obtained from their pleural fluid were extremely high. Finally, we diagnosed them as having malignant mesothelioma using an immunocytochemical technique and electronmicroscopy. We conclude that HRCT is helpful in the diagnosis of malignant mesothelioma, particularly in its early manifestation such as nodular opacities of interlobar fissures.}, } @article {pmid11301890, year = {2001}, author = {Schneider, J and Woitowitz, HJ}, title = {[Asbestos-induced malignant mesothelioma of the tunica vaginalis testis].}, journal = {Zentralblatt fur Chirurgie}, volume = {126}, number = {3}, pages = {229-232}, doi = {10.1055/s-2001-12499}, pmid = {11301890}, issn = {0044-409X}, mesh = {Aged ; Asbestos/*adverse effects ; Humans ; Lymphatic Metastasis ; Male ; Mesothelioma/*etiology/surgery ; Neoplasm Metastasis ; *Occupational Diseases ; *Occupational Exposure ; Occupations ; Testicular Neoplasms/*etiology/surgery ; }, abstract = {Since 1977 the diffuse malignant mesothelioma of the pleura and peritoneum caused by asbestos represents one of the most often compensated occupational cancers in Germany. Because of the probability of an asbestos-related etiology, it is considered as a "signal tumour", mainly indicating exposure to asbestos dust at the workplace. Two cases of histologically confirmed rare malignant mesothelioma of the tunica vaginalis testis are presented. Previous exposure to asbestos at the workplace is to be considered as a causal factor in both tumors. If cases of mesothelioma occur the criteria for indicating an occupational disease (No. 4105 of the German Law of Occupational Diseases, BKV) are fulfilled.}, } @article {pmid11296533, year = {2001}, author = {Manna, P and Comba, P}, title = {[Communicating with health authorities and the public about asbestos risk in Biancavilla (CT)].}, journal = {Epidemiologia e prevenzione}, volume = {25}, number = {1}, pages = {28-30}, pmid = {11296533}, issn = {1120-9763}, mesh = {Asbestosis/*epidemiology ; Humans ; Information Services ; Italy ; Public Health ; Risk Factors ; }, abstract = {The high incidence of pleural mesothelioma observed in Biancavilla (Catania) is causally associated to the presence of amphybolic fibres in the volcanic rock used by the local construction industry. This paper examines risk communication in this setting, with respect to presentation of the epidemiologic findings and decision making in the field of environmental clean up. The central issues in communicating with health authorities have been evaluation of the causal link and connections between available knowledge and subsequent action. The public has been rapidly informed, through press and local broadcasting stations. It has been made clear that recommended interventions were of preventive nature, namely paving with asphalt roads that were previously paved with the local quarry's byproducts. It has been stated that expected benefits would be delayed in time. Compliance of the local community may be jeopardized by further delay in the implementation of this intervention.}, } @article {pmid11256861, year = {2001}, author = {Murai, Y}, title = {Malignant mesothelioma in Japan: analysis of registered autopsy cases.}, journal = {Archives of environmental health}, volume = {56}, number = {1}, pages = {84-88}, doi = {10.1080/00039890109604058}, pmid = {11256861}, issn = {0003-9896}, mesh = {Adolescent ; Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Asbestosis/complications/*epidemiology/*pathology ; Autopsy ; Child ; Child, Preschool ; Female ; Heart Neoplasms/complications/*epidemiology/*pathology ; Humans ; Infant ; Japan/epidemiology ; Male ; Mesothelioma/complications/*epidemiology/*pathology ; Middle Aged ; Occupational Exposure/adverse effects/analysis ; *Pericardium ; Peritoneal Neoplasms/complications/*epidemiology/*pathology ; Pleural Neoplasms/complications/*epidemiology/*pathology ; Population Surveillance ; *Registries ; Sex Distribution ; Testicular Neoplasms/complications/*epidemiology/*pathology ; }, abstract = {In the Annual of the Pathological Autopsy Cases in Japan, issued by the Japanese Society of Pathology from 1958 to 1996, a total of 1,846 (0.17%) malignant mesothelioma cases (1,287 male, 558 female, 1 unknown) were registered among 1,056,259 autopsy cases. The frequency of mesothelioma (number of cases/total autopsy cases) was 0.10% (461/440,334) for the term 1958-1979, 0.18% (716/390,124) for 1980-1989, and 0.30% (669/225,801) for 1990-1996; the frequency of cases increased significantly over the time periods (p < .0001). Among 1,785 cases for which tumor sites were ascertained, there were 1,213 pleural mesothelioma (68.0%), 431 peritoneal (24.1%), 108 pericardial (6.1%), 6 tunica vaginalis testis (0.3%), and 28 "others" (1.6%). Histological cell type was noted in 598 cases; 245 (41.0%) were epithelial, 168 (28.1%) were biphasic, and 185 (30.9%) were sarcomatous. Seventy-three (0.007%) cases of malignant mesothelioma with asbestosis were found during the entire 39-y period. The frequency of those with asbestosis (number of cases/total autopsy cases) was 0.001% (5/440,334) for the term 1958-1979, 0.006% (27/390,124) for 1980-1989, and 0.018% (41/225,801) for 1990-1996; this increase over time was statistically significant (p < .0001). Researchers expect that cases of asbestos-related mesothelioma will increase in Japan in the future. Tumor sites and histological cell types of mesothelioma with asbestosis did not differ from those in individuals without asbestosis.}, } @article {pmid11254815, year = {2001}, author = {, }, title = {Statement on malignant mesothelioma in the United Kingdom.}, journal = {Thorax}, volume = {56}, number = {4}, pages = {250-265}, pmid = {11254815}, issn = {0040-6376}, mesh = {Asbestos/*adverse effects ; Diagnosis, Differential ; Humans ; Incidence ; *Lung Neoplasms/diagnosis/etiology/therapy ; Medical History Taking ; *Mesothelioma/diagnosis/etiology/therapy ; Neoplasm Staging/methods ; *Occupational Diseases/diagnosis/etiology/therapy ; *Peritoneal Neoplasms/diagnosis/etiology/therapy ; *Pleural Neoplasms/diagnosis/etiology/therapy ; Prognosis ; Referral and Consultation ; Survival Analysis ; Tomography, X-Ray Computed ; Workers' Compensation ; }, } @article {pmid11249674, year = {1999}, author = {Schwarzenberger, P and Byrne, P and Kolls, JK}, title = {Immunotherapy-based treatment strategies for malignant mesothelioma.}, journal = {Current opinion in molecular therapeutics}, volume = {1}, number = {1}, pages = {104-111}, pmid = {11249674}, issn = {1464-8431}, mesh = {Animals ; Antigens, CD/metabolism ; B7-1 Antigen/metabolism ; B7-2 Antigen ; Cancer Vaccines/isolation & purification/therapeutic use ; Clinical Trials as Topic ; Cytokines/metabolism ; Ganciclovir/therapeutic use ; Genetic Therapy/methods ; Histocompatibility Antigens/metabolism ; Humans ; Immunity, Cellular ; Immunologic Factors/therapeutic use ; Immunotherapy/*methods ; Membrane Glycoproteins/metabolism ; Mesothelioma/immunology/*therapy ; Mice ; Pleural Neoplasms/immunology/*therapy ; Simplexvirus/enzymology/genetics ; Thymidine Kinase/genetics ; }, abstract = {Malignant mesothelioma (MM) is a tumor of the pleura with an etiology that has been strongly linked to previous asbestos exposure. It is an almost universally fatal disease, regardless of tumor stage at the time of diagnosis. Current treatment modalities include surgery, chemotherapy and radiation therapy, although in some clinical trials none of these modalities have proven to be superior to no treatment at all. Knowledge of the tumor biology and immunology of this disease is insufficient, although several studies suggest feasibility and success for immunotherapeutic strategies. In this article, we review previous work and describe novel therapeutic approaches utilizing biological response modification for MM.}, } @article {pmid11245743, year = {2001}, author = {Dumortier, P and Coplü, L and Broucke, I and Emri, S and Selcuk, T and de Maertelaer, V and De Vuyst, P and Baris, I}, title = {Erionite bodies and fibres in bronchoalveolar lavage fluid (BALF) of residents from Tuzköy, Cappadocia, Turkey.}, journal = {Occupational and environmental medicine}, volume = {58}, number = {4}, pages = {261-266}, pmid = {11245743}, issn = {1351-0711}, mesh = {Adult ; Asbestos, Amphibole ; Body Burden ; Bronchoalveolar Lavage Fluid/*chemistry ; Case-Control Studies ; *Environmental Exposure ; Female ; Humans ; Male ; Mesothelioma/*etiology ; Microscopy, Electron ; Middle Aged ; Mineral Fibers ; Peritoneal Neoplasms/etiology ; Pleural Neoplasms/*etiology ; Soil Pollutants/analysis ; Turkey ; Zeolites/*analysis ; }, abstract = {OBJECTIVES: The high incidence of malignant mesothelioma in some villages of Cappadocia (Turkey) is due to environmental exposure to erionite fibres. The aim was to evaluate the fibre burden in bronchoalveolar lavage fluid (BALF) from inhabitants of an erionite village and compare it with Turkish subjects with or without environmental exposure to tremolite asbestos.

METHODS: Ferruginous bodies (FBs) and fibres were measured and analyzed by light and transmission electron microscopy (TEM) in the BALF of 16 subjects originating from Tuzköy.

RESULTS: FBs were detected in the BALF of 12 subjects, with concentrations above 1 FB/ml in seven of them. Erionite was the central fibre of 95.7% of FBs. Erionite fibres were found in the BALF of all subjects, by TEM, and these fibres were low in Mg, K, and Ca compared with erionite from Tuzköy soil. The mean concentration of erionite fibres in BALF was similar to that of tremolite fibres in Turks with environmental exposure to tremolite. The proportion of fibres longer than 8 microm in BALF represented 35.6% for erionite compared with 14.0% for tremolite. The asbestos fibre concentrations in erionite villagers was not different from that in Turks without environmental exposure to tremolite.

CONCLUSION: Analysis of BALF gives information about fibre retention in populations environmentally exposed to erionite for whom data on fibre burden from lung tissue samples are scarce. This may apply to exposed Turks having emigrated to other countries.}, } @article {pmid11243900, year = {2001}, author = {Rizzo, P and Bocchetta, M and Powers, A and Foddis, R and Stekala, E and Pass, HI and Carbone, M}, title = {SV40 and the pathogenesis of mesothelioma.}, journal = {Seminars in cancer biology}, volume = {11}, number = {1}, pages = {63-71}, doi = {10.1006/scbi.2000.0347}, pmid = {11243900}, issn = {1044-579X}, support = {CA 77220/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Humans ; Mesothelioma/epidemiology/therapy/*virology ; Neoplasms, Mesothelial/epidemiology/therapy/*virology ; Papillomavirus Infections/epidemiology/therapy/*virology ; Simian virus 40/*pathogenicity ; Tumor Virus Infections/epidemiology/therapy/*virology ; }, abstract = {Malignant mesothelioma, a tumor of the pleura, pericardium, and peritoneum, is presently a worldwide problem. Current therapy is ineffective in slowing the course of the disease, and median survival from the time of diagnosis is rarely greater than 1 year. While the tumor was almost unknown prior to the second half of the twentieth century, it is presently responsible for more than 2000 deaths per year in the US alone. Mesothelioma is frequently associated with exposure to asbestos, but the incidence of cases involving individuals with low levels of asbestos exposure is increasing. For this reason, there has been much interest in studying whether there are alternative factors that act alone or in conjunction with asbestos in producing this malignancy. In the last decade, simian virus 40 (SV40) has become the most notable suspected agent.}, } @article {pmid11243897, year = {2001}, author = {Testa, JR and Giordano, A}, title = {SV40 and cell cycle perturbations in malignant mesothelioma.}, journal = {Seminars in cancer biology}, volume = {11}, number = {1}, pages = {31-38}, doi = {10.1006/scbi.2000.0344}, pmid = {11243897}, issn = {1044-579X}, mesh = {Animals ; Cell Cycle/*physiology ; Cyclin-Dependent Kinase Inhibitor p16/metabolism ; Humans ; Mesothelioma/metabolism/pathology/*virology ; Neoplasms, Mesothelial/metabolism/*virology ; Protein Binding ; Proteins/metabolism ; Retinoblastoma Protein/metabolism ; Simian virus 40/*physiology ; Tumor Suppressor Protein p14ARF ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {Although epidemiological findings have established that exposure to asbestos fibers is the major cause of malignant mesothelioma (MM), recent studies have implicated simian virus 40 (SV40) in the etiology of some of these tumors. Cytogenetic and molecular genetic evidence suggests that multiple somatic genetic events are required for tumorigenic conversion of a mesothelial cell. As with many other types of cancer, in MM critical oncogenic events exert their action via perturbations of the cell cycle. Interactions between the retinoblastoma (Rb) family of proteins and oncoproteins encoded by SV40 lead to cell cycle alterations. Likewise, inhibition of the p53 tumor suppressor by SV40 can inactivate a crucial cell cycle checkpoint, thereby permitting cells to undergo mitosis regardless of the presence of DNA damage. Many MMs exhibit loss and/or inactivation of the tumor suppressors p16(INK4a)and p14(ARF), components of the pRb and p53 cell cycle regulatory pathways, respectively. Recent investigations have demonstrated that SV40 large T antigen, isolated from frozen biopsies of human MM specimens, binds to and inactivates various tumor suppressor gene products such as pRb and p53. In this review, we discuss how SV40-oncosuppressor interactions can lead to functional alterations of the pRb- and p53-dependent cell cycle regulatory pathways and thereby contribute to neoplastic transformation of human mesothelial cells.}, } @article {pmid11242699, year = {2001}, author = {Chaturvedi, S and Chaturvedi, S}, title = {Carcinogenicity of asbestos: convincing evidence, conflicting interests.}, journal = {The National medical journal of India}, volume = {14}, number = {1}, pages = {43-46}, pmid = {11242699}, issn = {0970-258X}, mesh = {Asbestos/*adverse effects ; Gastrointestinal Neoplasms/epidemiology/*etiology ; Humans ; India ; Lung Neoplasms/epidemiology/*etiology ; Mesothelioma/epidemiology/*etiology ; Occupational Exposure/adverse effects ; Risk Factors ; }, abstract = {In spite of hard epidemiological and clinical evidence associating asbestos fibre with asbestosis and cancer, the issue is controversial and likely to remain so. The focus is now shifting to non-occupational exposure, differential risk to various asbestos fibre types and the relatively low level of carinogenicity of the chrysotile form. This creates further space for scientific debate and the opportunity to form a considered opinion. However, the situation may take a worrisome turn if some of these scientific inquiries are used by market forces to their advantage. A look at the history of corporate activities in asbestos-related research reveals a disturbing trend. Information that was made available, through legal interventions, clearly shows how for half a century the asbestos industry in collaboration with some academic leaders of occupational medicine successfully suppressed evidence against asbestos. In developing countries, extensive and aggressive marketing continues by chrysotile producers, mainly Canadian companies. There is renewed pressure on this part of the world since new use of asbestos has been almost completely discontinued in the developed countries as a result of public pressure and state prohibitions. In this scenario, relaxation of public health control over any form of asbestos should be opposed. It is extremely dangerous and scientifically untenable to say that chrysotile asbestos can be used without risk. It has been identified as a potent human carcinogen, and remains so. However, some restraint must be exercised while dealing with asbestos that has already been released into the environment. Disturbing it unnecessarily may cause more harm than good.}, } @article {pmid11241559, year = {2001}, author = {Rödelsperger, K and Jöckel, KH and Pohlabeln, H and Römer, W and Woitowitz, HJ}, title = {Asbestos and man-made vitreous fibers as risk factors for diffuse malignant mesothelioma: results from a German hospital-based case-control study.}, journal = {American journal of industrial medicine}, volume = {39}, number = {3}, pages = {262-275}, doi = {10.1002/1097-0274(200103)39:3<262::aid-ajim1014>3.0.co;2-r}, pmid = {11241559}, issn = {0271-3586}, mesh = {Aged ; Asbestos/*adverse effects ; Case-Control Studies ; Germany ; Humans ; Lung Neoplasms/*etiology ; Male ; Manufactured Materials/*adverse effects ; Mesothelioma/*etiology ; Middle Aged ; Occupational Exposure/adverse effects ; Risk Factors ; Time Factors ; }, abstract = {BACKGROUND: This study examines the role of occupational factors in the development of diffuse malignant mesothelioma with special emphasis on the dose-response relationship for asbestos and on the exposure to man-made vitreous fibers (MMVFs).

METHODS: One hundred and twenty-five male cases, diagnosed by a panel of pathologists, were personally interviewed concerning their occupational and smoking history. The same number of population controls (matched for sex, age and region of residence) underwent similar interviews by trained interviewers. Odds ratios (OR) were calculated for an expert-based exposure index using conditional logistic regression.

RESULTS: Exposure to asbestos shows the expected sharp gradient with an OR of about 45 for a cumulative exposure > 1.5 fiber years (arithmetic mean 16 fiber years). A significant OR was calculated even for the lowest exposure category "> 0 - < or = 0.15 fiber years". Although the mean cumulative exposure to MMVF is roughly 10% of the exposure to asbestos, an increased OR is observed in an ever/never evaluation. This observation is heavily hampered by methodical problems. A corresponding case-control study was performed using a lung tissue fiber analysis in addition to interviews. Both interviews and the lung tissue analysis yielded similar OR levels between the reference and the maximum exposure intervals.

CONCLUSIONS: Despite a possible influence as a result of selection and information bias, our results confirm the previously reported observation of a distinct dose-response relationship even at levels of cumulative exposure below 1 fiber year. Moreover, the study confirms that asbestos is a relevant confounder for MMVF. A causal relationship between exposure to MMVF and mesothelioma could neither be detected nor excluded, as in other studies.}, } @article {pmid11240810, year = {1999}, author = {Heller, DS and Gordon, RE and Clement, PB and Turnnir, R and Katz, N}, title = {Presence of asbestos in peritoneal malignant mesotheliomas in women.}, journal = {International journal of gynecological cancer : official journal of the International Gynecological Cancer Society}, volume = {9}, number = {6}, pages = {452-455}, doi = {10.1046/j.1525-1438.1999.99060.x}, pmid = {11240810}, issn = {1525-1438}, abstract = {Heller DS, Gordon RE, Clement PB, Turnnir R, Katz N. Presence of asbestos in peritoneal malignant mesotheliomas in women. Asbestos plays a causal role in pleural mesotheliomas. The role in peritoneal mesotheliomas is less clear, particularly in women, who are less likely to have an exposure history. Seven peritoneal malignant mesotheliomas in women with no recorded asbestos exposure were analyzed in this report. Tissue digestion was performed on paraffin blocks of tumor. Transmission electron microscopy, energy-dispersive spectroscopy, and electron diffraction were performed for tissue fiber burden and fiber identification. Asbestos fiber burdens were present in 6 cases. Two showed crocidolite, 2 showed chrysotile, one showed chrysotile and amosite, and one showed chrysotile and tremolite. Fiber burdens ranged from 56,738 to 1,963,250 fibers per gram wet weight tissue. All fibers counted were between 1 and 5 microns. This study demonstrates asbestos in peritoneal mesotheliomas in women. Asbestos may play a role in the development of these tumors.}, } @article {pmid11233577, year = {2000}, author = {, }, title = {[Analysis of occupational exposure to asbestos in cases of mesothelioma registered in Romagna (1986-1998)].}, journal = {La Medicina del lavoro}, volume = {91}, number = {6}, pages = {575-586}, pmid = {11233577}, issn = {0025-7818}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestosis/*epidemiology ; Female ; Heart Neoplasms/*epidemiology ; Humans ; Italy ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Occupational Diseases/*epidemiology ; Occupational Exposure/*statistics & numerical data ; Pericardium ; Peritoneal Neoplasms/*epidemiology ; Pleural Neoplasms/*epidemiology ; Prevalence ; Registries ; }, abstract = {The aim of this study was to evaluate the prevalence and major correlates of occupational exposure to asbestos among the 125 cases of mesothelioma of the pleura, peritoneum, and pericardium registered in the Romagna Region of Italy between 1986 and 1998. Adequate occupational information was obtained for 122 (98%) cases. Among these, the male:female ratio was 81:41 (2.0), the median age was 68 years (range, 25-92), and the pleural location accounted for 96 (79%) cases. According to job history, 61 (50%) cases had had definite (23), probable (12), and possible (26) occupational exposure to asbestos. The probability (multiple logistic regression estimate) was greater for males (odds ratio, 10.8) but decreased for cases with mesothelioma of the peritoneum and pericardium (0.21) as well as those above the median age (0.38). Time period, residence, mode of diagnosis (histology, cytology, other), source of information (patient, wife/husband, others), and smoking habits exerted no independent effect. For 35 (57%) cases, occupational exposure was related to asbestos pollution of the workplace and not to the specific work task. Cases with definite, probable, and possible occupational exposure showed no significant difference in the distribution (Kruskal-Wallis test) by year of initial employment at risk, duration of exposure, and latency (median, 36 years). Occupational exposure occurred in a total of 22 workplaces. Three of these accounted for 21 (34%) cases. Multiple (> or = 2) cases (total 27 or 44%) were observed in six workplaces.}, } @article {pmid11233575, year = {2000}, author = {Ascoli, V and Fantini, F and Carnovale Scalzo, C and Blasetti, F and Bruno, C and Di Domenicantonio, R and Lo Presti, E and Pasetto, R and Nardi, F and Comba, P}, title = {[Malignant mesothelioma in the industrial area of Colleferro].}, journal = {La Medicina del lavoro}, volume = {91}, number = {6}, pages = {547-564}, pmid = {11233575}, issn = {0025-7818}, mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Incidence ; Italy ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Occupational Diseases/*epidemiology ; *Occupational Exposure ; Peritoneal Neoplasms/*epidemiology ; Pleural Neoplasms/*epidemiology ; }, abstract = {The study describes the occurrence of pleural and peritoneal malignant mesothelioma in the Colleferro industrial area (Province of Rome, 9 municipalities, population 63,000, period 1993-98) which is the site of a large chemical plant (BPD) producing organic chemicals, acid mixtures, insecticides, explosives and dynamite, and was involved in manufacturing/maintenance of railroad rolling stock. Asbestos was extensively used in these plants in the past. Mesothelioma cases were actively searched from data in files of pathology archives, hospital admission and discharge (records), and death certificates recorded at local health authority register. 23 potential cases were identified for whom clinical charts and pathological slides were reviewed. A multidisciplinary evaluation of all collected information confirmed 18 cases of cyto-histologically proven malignant mesothelioma (pleural/peritoneal ratio of 2.75:1) among residents and/or workers at BPD. The remaining 5 cases were defined as not mesothelioma; however, two were cases of lung cancer (both occupationally exposed to asbestos). All subjects with malignant mesothelioma had been occupationally exposed to asbestos (14 males and 3 females), except one (1 female with domestic exposure). No mesothelioma case was attributable to environmental exposure. Of the 17 cases with occupational asbestos exposure, 15 occurred in BPD workers employed in manufacturing/maintenance of railroad rolling stock (3 cases), general maintenance services (5 cases), or in the armaments sector (7 cases) and 2 in residents but not BPD workers (1 baker, 1 pipefitter). The incidence rate in residents of the 9 municipalities was 5.5 in males and 1.3 in females (standardized on the Italian population x100,000, census 1981). For Colleferro municipality only, the incidence was 10.1 in males and 4.1 in females, which are the highest rates reported so far in Italy. Besides confirming the risk of mesothelioma risk in railroad rolling stock manufacturing and asbestos-insulated pipe maintenance workers, this study identifies a cluster of malignant mesothelioma in explosives production workers.}, } @article {pmid11232111, year = {2000}, author = {Krismann, M and Müller, KM and Jaworska, M and Johnen, G}, title = {Severe chromosomal aberrations in pleural mesotheliomas with unusual mesodermal features. Comparative genomic hybridization evidence for a mesothelioma subgroup.}, journal = {The Journal of molecular diagnostics : JMD}, volume = {2}, number = {4}, pages = {209-216}, pmid = {11232111}, issn = {1525-1578}, mesh = {Aged ; *Chromosome Aberrations ; Chromosome Mapping ; Female ; Humans ; Immunohistochemistry ; Male ; Mesothelioma/chemistry/diagnosis/*genetics/pathology ; Middle Aged ; Nucleic Acid Hybridization ; Pleural Neoplasms/chemistry/diagnosis/*genetics/pathology ; }, abstract = {Malignant mesotheliomas are tumors known for their extensive heterogeneity. Apart from the three classical patterns, predominantly epithelioid, sarcomatoid, and biphasic, some rare variants do exist. In some cases, one can find uncommon additional mesodermal tumor components. These tumors have previously been called "mesodermomas" and, like regular mesotheliomas, are usually associated with a previous asbestos exposure. We examined eight cases of mesodermomas by light microscopy, immunohistochemistry and comparative genomic hybridization (CGH). Besides biphasic and epithelioid areas, unusual epithelial, chondroid, osseous, or even angioblastic elements may be found to varying degrees. Immunohistochemical analysis shows similar staining results as with regular mesotheliomas. CGH reveals a high number of chromosomal imbalances (16.5 per case; range, 11-27). In 10 classical biphasic mesotheliomas that served as a control, defects of comparable number and severity could not be detected (8 per case; range, 2-16). The most frequent defects of mesodermomas (losses on 1p, 4pq, 9p, 13q, 14q, and gains on 1q and 15q), however, could also be found in mesotheliomas of the classical type. Thus, our results support the classification of the so-called mesodermomas as a separate tumor subgroup while maintaining the relationship to the classical mesotheliomas. Therefore, we propose to use the term mesodermoma for this subgroup.}, } @article {pmid11224994, year = {2001}, author = {Ho, L and Sugarbaker, DJ and Skarin, AT}, title = {Malignant pleural mesothelioma.}, journal = {Cancer treatment and research}, volume = {105}, number = {}, pages = {327-373}, doi = {10.1007/978-1-4615-1589-0_13}, pmid = {11224994}, issn = {0927-3042}, mesh = {Adult ; Aged ; Animals ; Anticarcinogenic Agents/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Asbestos/adverse effects ; Case-Control Studies ; Combined Modality Therapy ; Cricetinae ; Cytokines/therapeutic use ; Diagnostic Imaging ; Disease Progression ; Drug Contamination ; Female ; Genetic Therapy ; Humans ; Hyperthermia, Induced ; Interferons/therapeutic use ; Life Tables ; Male ; *Mesothelioma/diagnosis/epidemiology/etiology/pathology/prevention & control/therapy/virology ; Mice ; Mice, Nude ; Middle Aged ; Multicenter Studies as Topic ; Neoplasm Staging/methods ; Neoplasms, Radiation-Induced/epidemiology/etiology ; Occupational Diseases/epidemiology/etiology ; Palliative Care ; Photochemotherapy ; Pleural Effusion, Malignant/etiology ; *Pleural Neoplasms/diagnosis/epidemiology/etiology/pathology/prevention & control/therapy/virology ; Poliovirus Vaccine, Inactivated ; Randomized Controlled Trials as Topic ; Risk Factors ; Simian virus 40/pathogenicity ; Survival Analysis ; Survival Rate ; Treatment Outcome ; Xenograft Model Antitumor Assays ; }, abstract = {Malignant pleural mesothelioma remains a difficult tumor to treat, much less cure. Currently, the best chance for long-term survival lies with early diagnosis and aggressive surgical extirpation, but given the typically long delay between the onset of symptoms and diagnosis, this is only possible with a high index of suspicion and an aggressive diagnosis workup. Early referral to a tertiary center experienced in the treatment of MPM may be important for several reasons: (1) decreased risk of tumor spread along multiple thoracenesis/biopsy tracts, (2) the availability of specialized pathologic assays for definitive diagnosis, (3) the availability of critical staging modalities (aggressive mediastinoscopy +/- thoracoscopy, MRI scans performed according to specific mesothelioma protocols, and perhaps PET scans), (4) surgical experience with pleurectomy/decortication and/or extrapleural pneumonectomy, that may decrease morbidity and mortality, and (5) the availability of novel adjuvant protocols. Single-modality therapy is unlikely to result in long-term survival. Aggressive surgery is required for optimal debulking, and extrapleural pneumonectomy may offer better local control compared with pleurectomy/ecortication. Delivery of optimal radiation schedules, which may involve large fractions as well as large total doses, is limited by the presence of nearby dose-limiting structures. Current chemotherapy is severely lacking in producing objective responses and improved survival although gemcitabine and IL-2 may be active agents to be combined with radiation and/or other agents. Hyperthermia, photodynamic therapy, intracavitary therapy, and gene therapy are all relatively new techniques under active investigation that should be supported by enrollment in on-going protocols. Predictably, many of these techniques provide greater benefit when used in the setting of adjuvant protocols or minimal residual disease, emphasizing the importance of multimodality therapy.}, } @article {pmid11219202, year = {2000}, author = {Merler, E and Ercolanelli, M and de Klerk, N}, title = {[Identification and mortality of Italian emigrants returning to Italy after having worked in the crocidolite mines at Wittenoon Gorge, Western Australia].}, journal = {Epidemiologia e prevenzione}, volume = {24}, number = {6}, pages = {255-261}, pmid = {11219202}, issn = {1120-9763}, mesh = {Adult ; Asbestos, Crocidolite/*adverse effects ; Asbestosis/epidemiology/mortality ; Cardiovascular Diseases/mortality ; Cause of Death ; Cohort Studies ; Digestive System Diseases/mortality ; Europe/ethnology ; Female ; Follow-Up Studies ; Humans ; Italy/epidemiology/ethnology ; Lung Neoplasms/etiology/mortality ; Male ; Mesothelioma/etiology/mortality ; Middle Aged ; Mining/*statistics & numerical data ; Mortality ; Occupational Exposure ; Peritoneal Neoplasms/etiology/mortality ; Pleural Neoplasms/etiology/mortality ; Transients and Migrants/*statistics & numerical data ; Western Australia ; }, abstract = {The crocidolite mine at Wittenoom Gorge, Western Australia, has been active from 1943 to 1966, and managed by Australian Blue Asbestos Ltd (ABA). Migrants constituted the large majority of workers. The list of workers is composed of 6,911 subjects (6,501 males). In it we identified 1,102 Italians (1,069 males) and completed the follow up for those previously lost, remained in Australia or returned to Italy. Up to 1997, 302 subjects (301 males) definitively resettled in Italy, almost always returning to their community of origin. The median length of work at Wittenoom for those resettled was 17.8 months. The resettled subjects are spread around Italy, and 112 subjects (37%) already died. We compared the mortality rates of those returned to Italy to the rates of the male Italian population. Migrants were subjected to a strong selection before departure and were the target of a surveillance program during work at Wittenoom: however, for those resettled, instead of a healthy migrant effect, we observed an overmortality, mainly due to deaths from penumoconiosis (10 deaths vs 0.38 expected), from respiratory tumours (3 deaths from pleural mesothelioma and 4 from primary peritoneal tumours; an excess of lung cancers, SMR 1.28, 95% CI 0.72-2.11, and an excess of undefined caused of deaths (SMR 6.29, 95% CI 2.52-12.96). The study suggests that asbestos-related diseases and deaths have been observed among those resettled to Italy. In order to increase the precision of the follow up of the Wittenoom cohort, a search outside Australia should be carried out in some European countries for workers whose vital status was unconfirmed. Survivors in Italy are suffering from asbestosis, jeopardizing their life, and are at risk of cancer, but few have received information, actions aimed at reducing the accumulated risk, or compensation. Italy had a multi-million number of migrants for work, and an important percentage of migrants is returned to Italy: the effects of occupational exposures to adverse agents should be expected, but this topic has received up to now little attention.}, } @article {pmid11216913, year = {2001}, author = {Schneider, J and Rödelsperger, K and Brückel, B and Kleineberg, J and Woitowitz, HJ}, title = {Pleural mesothelioma associated with indoor pollution of asbestos.}, journal = {Journal of cancer research and clinical oncology}, volume = {127}, number = {2}, pages = {123-127}, doi = {10.1007/s004320000175}, pmid = {11216913}, issn = {0171-5216}, mesh = {Air Pollution, Indoor/*adverse effects ; Asbestos/*adverse effects ; Carcinogens/*adverse effects ; Female ; Humans ; Mesothelioma/chemically induced/*etiology ; Middle Aged ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/chemically induced/*etiology ; }, abstract = {This case report concerns a 46-year-old woman, dying from histologically confirmed diffuse malignant mesothelioma after asbestos exposure, which was only caused by indoor pollution from crocidolite-containing spray asbestos in building materials. There was no other known occupational or environmental asbestos exposure during her life. The lung tissue fibre analysis by light microscopy showed significantly increased concentrations of ferruginous bodies (3162 FB per gram of wet lung tissue). By use of scanning transmission electron microscopy, clearly increased concentrations of amphibole fibres (8.6 x 10(6) fibres longer than 1 microm and 0.6 x 10(6) fibres longer than > or =5 microm per gram dry tissue), mainly classified as crocidolite, were observed. The disease was attributed to indoor exposure to sprayed asbestos, which occurred during her work as a decorator in the studio of a warehouse.}, } @article {pmid11213409, year = {2000}, author = {Polverosi, R and Vigo, M and Citton, O}, title = {[Pleural and parenchymal lung diseases from asbestos exposure. CT diagnosis].}, journal = {La Radiologia medica}, volume = {100}, number = {5}, pages = {326-331}, pmid = {11213409}, issn = {0033-8362}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Asbestosis/*diagnostic imaging/pathology ; Environmental Exposure/*adverse effects ; Female ; Humans ; Lung Neoplasms/diagnostic imaging/etiology ; Male ; Mesothelioma/diagnostic imaging/etiology ; Middle Aged ; Pleural Diseases/*diagnostic imaging/*etiology/pathology ; Pleural Neoplasms/diagnostic imaging/etiology ; Retrospective Studies ; *Tomography, X-Ray Computed ; }, abstract = {INTRODUCTION: We report the CT findings of parenchymal and pleural diseases in a group of patients with a history of asbestos exposure, excluding lung cancer (which is not typical in this subjects) and asbestosis (which is a parenchymal fibrosis).

MATERIAL AND METHODS: We retrospectively reviewed a series of CT examinations (conventional, helical and high resolution scans) of 21 patients examined from 1995 to 1999. They had pleural plaques (10), round atelectasis (2) and malignant pleural mesothelioma (9). All patients had a history of direct or indirect asbestos exposure, except one with malignant pleural mesothelioma. We evaluated the following CT findings: nodular, plaque or uniform pleural thickening; pleural calcifications; pleural thickening less or greater than 1 cm; pleural margins (regular, polycyclic, spiculated); localization (uni/bilateral hemithorax); distribution (upper, medium or lower region); pulmonary, mediastinal and diaphragmatic involvement; fissural involvement; pleural effusion; lymph node enlargement; lung mass with the comet-tail sign; lung volume (normal, reduced, increased).

RESULTS: Pleural plaques were always bilateral and less than 1 cm thick, with calcifications in 80% of the cases. Margins were always regular, polycyclic in 40% of the patients and never irregular. The pulmonary pleura in the mid-chest was involved in cell cases the diaphragmatic pleura in the 50% of the cases and the upper and lower regions in 60% and 80% of the patients, respectively. Round atelectasis (3 cases in 2 patients) was always shown as a parenchymal mass in the lower lobes, posteriorly or posteromedially, with adjacent pleural thickening; its diameter ranged 4.4-6 cm and there was the comet-tail sign. In malignant pleural mesothelioma we always found pleural effusion, with unilateral pleural effusion being the only sign in 2 patients. Other findings were pleural nodules (77.7%), with spiculated (22.2%) and polycyclic (77.7%) margins, more than 1 cm in diameter. The disease was always unilateral. The parenchymal pleural was involved in 77.7% of the cases while the mediastinal and diaphagmatic pleura were involved in 44.4% of the patients. Fissural involvement was demonstrated in 66.6% of the patients. Lymph nodes were enlarged in 66.6% of the cases. The volume of the affected hemithorax was increased (22.2%), decreased (44.4%) or normal (33.3%).

DISCUSSION AND CONCLUSIONS: The presence of pleural plaques is a specific sign of asbestos exposure. Round atelectasis may also indicate asbestos exposure, but it can be found in many diseases with pleural inflammation, such as tuberculous effusion, trauma, pulmonary infarct, congestive heart failure, coronary artery bypass. The CT patterns of these two diseases are typical and no other finding is necessary to confirm the diagnosis. CT-guided needle biopsy is needed only if the round atelectasis has an atypical appearance on CT images, that is without the comet-tail sign. Malignant pleural mesothelioma is strongly associated with previous occupational exposure and presents typical CT findings only in an advanced stage (irregular and nodular pleural thickening, pleural effusion, mediastinal and pulmonary contraction for tumor encasement, parenchymal and lymph node metastases), but the differential diagnosis with pleural metastatic disease can be difficult. CT plays an important role in tumor assessment but biopsy is necessary for lesion characterization.}, } @article {pmid11211478, year = {2000}, author = {De Rienzo, A and Testa, JR}, title = {Recent advances in the molecular analysis of human malignant mesothelioma.}, journal = {La Clinica terapeutica}, volume = {151}, number = {6}, pages = {433-438}, pmid = {11211478}, issn = {0009-9074}, support = {CA 06927/CA/NCI NIH HHS/United States ; CA 45745/CA/NCI NIH HHS/United States ; }, mesh = {Asbestosis/*complications ; Gene Deletion ; Genes, Tumor Suppressor/genetics ; Humans ; Mesothelioma/*etiology/*genetics ; Papillomavirus Infections/complications ; Pleural Neoplasms/*etiology/*genetics ; Simian virus 40 ; Tumor Virus Infections/complications ; }, abstract = {PURPOSE: To evaluate the role of asbestos, somatic genetic alterations, and simian virus 40 (SV40) in the formation of malignant mesothelioma (MM).

DESIGN: To review recent cytogenetic and molecular genetic advances in MM.

RESULTS: Exposure to asbestos is a major factor contributing to the development of most MMs. The accumulation of recurrent cytogenetic deletions in most MMs suggests a multistep process in this malignancy characterized by the loss and/or inactivation of multiple tumor suppressor genes (TSGs). Karyotypic, comparative genomic hybridization (CGH), and loss of heterozygosity (LOH) analyses of MMs have demonstrated frequent deletions of specific chromosomal regions within 1p, 3p, 6q, 9p, 13q, 15q, and 22q. Positional candidate gene approaches have identified TSGs within two of these regions, i.e., CDKN2A at 9p21 and NF2 at 22q12, which are frequently altered in MMs. In addition, recent studies have demonstrated the presence and expression of SV40 in many MMs. Proposed mechanisms by which asbestos and SV40 contribute to the development of MM are reviewed.

CONCLUSIONS: The identification of new TSGs involved in MM and understanding the role of these genes and of SV40 in the pathogenesis of this malignancy may lead to design of more effective therapeutic strategies.}, } @article {pmid11202027, year = {2001}, author = {Yeung, P and Rogers, A}, title = {An occupation-industry matrix analysis of mesothelioma cases in Australia 1980-1985.}, journal = {Applied occupational and environmental hygiene}, volume = {16}, number = {1}, pages = {40-44}, doi = {10.1080/104732201456113}, pmid = {11202027}, issn = {1047-322X}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Australia/epidemiology ; Carcinogens/*adverse effects ; Humans ; Industry ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; *Occupational Exposure ; Occupations/*statistics & numerical data ; Risk Factors ; }, abstract = {Australia has one of the highest national incidences of mesothelioma in the world and the rate is still rising. An industry-occupation matrix analysis was conducted for the 858 mesothelioma cases that were reported to the Australian Mesothelioma Surveillance Program between 1980 and 1985. Definite, probable, or possible occupational exposure had occurred in 57 percent (492/858) of the subjects. The primary asbestos production or manufacturing industry constituted the largest number of cases (137/492, 27.8%), followed by shipbuilding, repair and demolition (114/492, 23.2%), the building industry (69/492, 14.1%), and the railway locomotive construction and maintenance industry (47/492, 9.6%). Laborers constituted 14.8 percent (n = 73) of the occupations with a history of exposure to asbestos, followed by carpenters (13.0%, n = 64), boilermakers (10.6%, n = 52), and fitters/turners (8.1%, n = 40). The distribution of occupations in specific industries is presented in this article.}, } @article {pmid11201579, year = {2000}, author = {García-López, MP and Barrera-Rodríguez, R}, title = {[Malignant mesothelioma: clinical and radiological description of 45 cases with and without asbestos exposure].}, journal = {Salud publica de Mexico}, volume = {42}, number = {6}, pages = {511-519}, pmid = {11201579}, issn = {0036-3634}, mesh = {Adult ; Age of Onset ; Aged ; Asbestos/*adverse effects ; Chest Pain/etiology ; Cough/etiology ; Dyspnea/etiology ; Environmental Exposure/*statistics & numerical data ; Female ; Hemoptysis/etiology ; Humans ; Male ; Mesothelioma/diagnostic imaging/*epidemiology/etiology/pathology ; Mexico/epidemiology ; Middle Aged ; Neoplasms/genetics ; Occupational Exposure/statistics & numerical data ; Pleural Effusion, Malignant/diagnostic imaging/etiology ; Pleural Neoplasms/diagnostic imaging/*epidemiology/etiology/pathology ; Radiography ; Retrospective Studies ; }, abstract = {OBJECTIVE: Our aim was to identify and describe the main symptoms, clinical presentation, and radiographic changes in malignant mesothelioma (MM) patients.

MATERIAL AND METHODS: We reviewed the medical and X-ray records of all patients diagnosed with MM, admitted between 1991 and 1998 to the National Institute of Respiratory Diseases (INER), which is a governmental institution specialized in chest disease in Mexico City. The following data were collected: Age, occupation, asbestos exposure, latency, family history of cancer, clinical symptoms, and X-ray changes. Data are presented as percentages by sex and age group.

RESULTS: We found 45 cases of MM; in 80% of them a history of asbestos exposure could not be documented. The 51-60 years age group had the highest frequency of MM. Dispnea and chest pain were the presenting symptoms in most patients. Pleural effusion and pleural thickening were the X-ray abnormalities observed in 75% of the patients.

CONCLUSIONS: The clinical and radiographic findings among patients with MM without asbestos exposure were similar to those with a history of asbestos exposure.}, } @article {pmid11199380, year = {2000}, author = {Müller, KM and Fischer, M}, title = {Malignant pleural mesotheliomas: an environmental health risk in southeast Turkey.}, journal = {Respiration; international review of thoracic diseases}, volume = {67}, number = {6}, pages = {608-609}, doi = {10.1159/000056288}, pmid = {11199380}, issn = {0025-7931}, mesh = {Asbestos/*adverse effects/analysis ; Carcinogens/*adverse effects/analysis ; Environmental Exposure/*adverse effects ; Humans ; Mesothelioma/diagnostic imaging/*epidemiology/*etiology ; Pleural Neoplasms/diagnostic imaging/*epidemiology/*etiology ; Radiography ; Turkey/epidemiology ; }, } @article {pmid11198540, year = {2000}, author = {Kjellstrom, T and Smartt, P}, title = {Increased mesothelioma incidence in New Zealand: the asbestos-cancer epidemic has started.}, journal = {The New Zealand medical journal}, volume = {113}, number = {1122}, pages = {485-490}, pmid = {11198540}, issn = {0028-8446}, mesh = {Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects/economics ; Commerce/statistics & numerical data ; Ethnicity/statistics & numerical data ; Female ; Humans ; Incidence ; Lung Neoplasms/*epidemiology/etiology/mortality ; Male ; Mesothelioma/*epidemiology/etiology/mortality ; Middle Aged ; New Zealand/epidemiology ; Occupations ; Pleural Neoplasms/*epidemiology/etiology/mortality ; Regression Analysis ; Sex Distribution ; }, abstract = {AIMS: To examine the incidence and mortality patterns for malignant mesothelioma and pleural cancer in New Zealand between 1962-1996, and relate these to past use of asbestos.

METHODS: Data concerning cases of mesothelioma 1962-1996, deaths from pleural and lung cancers 1974-1996, and data on imports of raw asbestos and asbestos products were obtained from government registers and publications. Time trends were analysed using different models.

RESULTS: Mesothelioma incidence rates have increased progressively in New Zealand since the 1960s, and reached 25 per million for men in 1995. The increase follows an exponential model departing from a crude 'background rate' of 1-2 per million in 1984, and is particularly steep in males 50 to 60 years of age. The incidence is expected to double by 2010.

CONCLUSION: New Zealand has entered an unrivalled period of occupational cancer deaths resulting from past workplace exposure to airborne asbestos fibres. The steep rise in mesothelioma incidence is likely to be accompanied by increases in other asbestos related diseases such as lung cancer. The unique causal association between mesothelioma and asbestos may be used to monitor changes in the public health impact of these exposures. The notification by medical practitioners of all potential asbestos related conditions/exposures to the Occupational Safety and Health (OSH) service is of great importance.}, } @article {pmid11192543, year = {2000}, author = {Ozer, N and Shehu, V and Aytemir, K and Ovünç, K and Emre, S and Kes, S}, title = {Echocardiographic findings of pericardial involvement in patients with malignant pleural mesothelioma with a history of environmental exposure to asbestos and erionite.}, journal = {Respirology (Carlton, Vic.)}, volume = {5}, number = {4}, pages = {333-336}, pmid = {11192543}, issn = {1323-7799}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Blood Gas Analysis ; Carcinogens/*adverse effects ; Echocardiography ; Environmental Exposure/*adverse effects ; Female ; Humans ; Male ; Mesothelioma/*diagnostic imaging/*etiology/pathology ; Middle Aged ; Neoplasm Staging ; Pericardial Effusion/*diagnostic imaging/*etiology/pathology ; Pleural Neoplasms/*diagnostic imaging/*etiology/pathology ; Respiratory Function Tests ; Zeolites/*adverse effects ; }, abstract = {OBJECTIVE: The aim of the present study was to evaluate the pericardial involvement in patients with malignant mesothelioma caused by exposure to different minerals.

METHODOLOGY: Forty-two patients (mean age of 52 +/- 12 years) with malignant mesothelioma were examined with transthoracic echocardiography. Thirty-three (78.9%) patients had a history of environmental exposure to asbestos and nine (21.4%) had a history of environmental exposure to erionite.

RESULTS: In 19 (45.2%) patients with malignant pericardial mesothelioma, pericardial involvement was determined by echocardiography. The other 23 (54.8%) patients had no pericardial involvement. Pericardial effusion was detected in nine (64.3%) patients and pericardial effusion was small in six (14.3%) patients, moderate in one (2.4%) patient and large in two patients. Thickening of the pericardium was observed in eight (19%) patients. In another two (7.1%) patients pericardial calcification was observed. Among the 33 patients who had been exposed to asbestos, 15 (45.5%) had pericardial involvement, and among the nine patients with a history of exposure to erionite, four (44.4%) had pericardial involvement. There was no difference in terms of pericardial involvement in different stages of the tumour (P > 0.05).

CONCLUSIONS: Pericardial involvement is commonly seen in patients with malignant mesothelioma. Among patients exposed to asbestos or zeolite there was no difference in terms of pericardial involvement. Furthermore, pericardial involvement was not related with the stage of the tumour.}, } @article {pmid11189476, year = {2000}, author = {Gennaro, V and Montanaro, F and Lazzarotto, A and Bianchelli, M and Celesia, MV and Canessa, PA}, title = {[Mesothelioma registry of the Liguria region. Incidence and occupational etiology in a high risk area].}, journal = {Epidemiologia e prevenzione}, volume = {24}, number = {5}, pages = {213-218}, pmid = {11189476}, issn = {1120-9763}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Incidence ; Italy ; Male ; Mesothelioma/*epidemiology/*etiology ; Middle Aged ; Occupational Diseases/*epidemiology/*etiology ; Pleural Neoplasms/*epidemiology/*etiology ; *Registries ; Risk Factors ; }, abstract = {This paper presents the epidemiological analyses based on the first 5 years of activity of the Mesothelioma Registry of Liguria (REM). REM is a population-based cancer registry specialized in the study of both the incidence and etiology of primary pleural and peritoneal mesothelioma in Liguria (Italy). The REM completes normal clinical information with occupational and environmental anamnestic data in order to identify working and living areas at risk for asbestos-related pathologies. The REM started its activity in 1994 describing the incidence of pleural mesothelioma (PM) exclusively in the population resident in the city of Genoa (660,000 inhabitants); since 1996 the REM has studied the entire Liguria Region (1,640,000 inhabitants), where nearly 120 new cases of PM are diagnosed annually (20% are women). In the city of Genoa, between 1986-1987 and 1997-1998, PM crude incidence rate rose from 13.8 to 26.7 per 100,000 males over 40 years old. From 1994 to 1998 the REM registered 495 new patients with histologically (62%) and cytologically (9%) confirmed diagnosis of PM. 54% of them were immunocytohistochemically evaluated. Occupational information has been gathered for 248 subjects, i.e., 61% of cases with sure or probable diagnosis of PM. For 126 patients, occupational asbestos exposure (direct, indirect or only presence in the workplace) was identified on average 40 years before diagnosis. In particular, asbestos exposure was documented in shipyards, docks and cargo handling settings, building trades, iron and steel industries. Interestingly, during the same period (1955-1960), a large fraction of subjects without proved or declared direct asbestos exposure claimed to have worked in the same occupational settings. This suggests a possible unconscious indirect exposure to asbestos fibers in the workplace.}, } @article {pmid11153112, year = {2000}, author = {Pritchard, D}, title = {Was Charlemagne killed by his tablecloth?.}, journal = {Biologist (London, England)}, volume = {47}, number = {4}, pages = {170}, pmid = {11153112}, issn = {0006-3347}, mesh = {Asbestos/adverse effects/*history ; Carcinogens/adverse effects/*history ; *Famous Persons ; History, Medieval ; Humans ; Mesothelioma/chemically induced/history ; Pleural Neoplasms/chemically induced/history ; Pleurisy/etiology/*history ; }, } @article {pmid11139313, year = {2001}, author = {Creaney, J and McLaren, BM and Stevenson, S and Musk, AW and de Klerk, N and Robinson, BW and Lake, RA}, title = {p53 autoantibodies in patients with malignant mesothelioma: stability through disease progression.}, journal = {British journal of cancer}, volume = {84}, number = {1}, pages = {52-56}, pmid = {11139313}, issn = {0007-0920}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antibodies, Neoplasm/*blood ; Autoantibodies/*blood ; Blotting, Western ; Case-Control Studies ; Enzyme-Linked Immunosorbent Assay ; Female ; HT29 Cells/immunology ; Humans ; Male ; Mesothelioma/blood/*immunology ; Middle Aged ; Pleural Neoplasms/blood/*immunology ; Tumor Suppressor Protein p53/*immunology ; }, abstract = {Malignant mesothelioma (MM) generally occurs as a pleural tumour, related to the inhalation of asbestos fibres. It is highly aggressive and largely unresponsive to treatment. The incidence of MM is particularly high in Western Australia because of the extensive blue asbestos mining operations that occurred in the north of the state until 1966. MM is unusual in that mutations in the tumour suppressor gene p53 are rarely observed, whilst over-expression of p53 protein is common. As the level of antibodies directed against p53 is thought to be of prognostic value in some cancers and as MM is known to be immunogenic, we studied a cohort of Western Australian patients to determine the prevalence of anti-p53 antibodies and their value as diagnostic markers or prognostic indicators. 6/88 (7%) of patients had high titres (>2 SD above the mean of controls) of anti-p53 antibodies. There was no correlation between antibody titre and survival. Although 3/38 (8%) of sera obtained from patients exposed to asbestos but prior to a diagnosis of MM contained antibodies, the same proportion of sera obtained from patients exposed to asbestos but who remained disease free also contained antibodies (2/40; 8%). Sera collected sequentially demonstrated a profound temporal stability in the titre of anti-p53 antibodies in patients with MM throughout the course of their illness. These results show that anti-p53 antibodies are observed only at a low frequency in the sera of MM patients and where they do occur, their elicitation is an early event that may be unrelated to antigen load. The occurrence of anti-p53 antibodies does not serve as either a useful prognostic or diagnostic indicator in MM.}, } @article {pmid11133818, year = {2000}, author = {Faux, SP and Houghton, CE and Hubbard, A and Patrick, G}, title = {Increased expression of epidermal growth factor receptor in rat pleural mesothelial cells correlates with carcinogenicity of mineral fibres.}, journal = {Carcinogenesis}, volume = {21}, number = {12}, pages = {2275-2280}, doi = {10.1093/carcin/21.12.2275}, pmid = {11133818}, issn = {0143-3334}, mesh = {Animals ; Asbestos, Crocidolite/*toxicity ; Asbestos, Serpentine/*toxicity ; Carcinogens/*toxicity ; Cells, Cultured ; Epithelial Cells/cytology/*drug effects/metabolism ; ErbB Receptors/*genetics/metabolism ; Male ; Pleura/*cytology ; Rats ; Rats, Inbred F344 ; Up-Regulation ; Zeolites/*toxicity ; }, abstract = {Asbestos fibres have been shown to stimulate the mitogen-activated protein kinase signalling cascade in rat pleural mesothelial (RPM) cells after autophosphorylation of the epidermal growth factor receptor (EGFR). We examined if mineral fibres with known carcinogenicity can be discriminated from materials with less or no carcinogenicity by their ability to up-regulate expression of EGFR protein in RPM cells in vitro. Crocidolite and erionite, two fibrous preparations with marked potential to induce mesothelioma, were associated with increases in EGFR protein expression over sham controls, whereas chrysotile asbestos and milled (non-fibrous) crocidolite did not. Intense patterns of EGFR protein expression were linked to RPM cells phagocytosing long fibres. To determine the role of EGFR expression in these cells, we assessed cell proliferation using an antibody against proliferating cell nuclear antigen (PCNA) in combination with an antibody against EGFR. In these co-localization studies, cells showed intense staining for EGFR protein 24 h before being PCNA positive at 48 h. These results suggest that carcinogenic fibres induce EGFR and initiate cell signalling cascades in mesothelial cells, leading to cell proliferation and carcinogenesis.}, } @article {pmid11128884, year = {2000}, author = {Murai, Y and Kitagawa, M}, title = {Autopsy cases of asbestosis in Japan: a statistical analysis on registered cases.}, journal = {Archives of environmental health}, volume = {55}, number = {6}, pages = {447-452}, doi = {10.1080/00039890009604044}, pmid = {11128884}, issn = {0003-9896}, mesh = {Adult ; Age Distribution ; Aged ; Asbestosis/*epidemiology/etiology/*pathology ; Autopsy/*statistics & numerical data ; Chi-Square Distribution ; Female ; Humans ; Incidence ; Japan/epidemiology ; Male ; Middle Aged ; Occupational Diseases/*epidemiology/etiology/*pathology ; Occupational Exposure/adverse effects ; Registries ; Risk Factors ; Sex Distribution ; Survival Rate ; }, abstract = {There are 525 (484 male, 38 female, 3 unknown) autopsy cases with asbestosis registered in the Annual of the Pathological Autopsy Cases in Japan, which is issued by the Japanese Society of Pathology for the years 1958-1996. The frequency of asbestosis (number of cases/total autopsy cases) was 0.017% (76/440,334) for the 1958-1979 time period, 0.058% (226/390,124) for 1980-1989, and 0.099% (223/225,801) for 1990-1996. There was a significant increase in asbestosis cases across the three time periods (p < .0001). The number of asbestosis cases increased markedly among individuals who worked with asbestos products, as well as among those employed in asbestos-processing factories. The frequency of malignant tumors associated with asbestosis was 61.0% (320/525), and the frequency also increased across the three time periods, from 43.4% (33/76) to 62.8% (142/226) and 65.0% (145/223), respectively. Among the 525 cases with asbestosis, there were 174 lung cancers (33.1%), 73 malignant mesotheliomas (13.9%), 29 stomach cancers (5.5%), 14 liver cancers (2.7%), 9 prostatic cancers (1.7%), 8 malignant lymphomas (1.5%), 6 laryngeal cancers (1.1%), 4 pancreas cancers (0.8%), 3 rectal cancers (0.6%), and 28 other cancers (5.3%). The frequencies of lung cancer, malignant mesothelioma, and laryngeal cancer were significantly higher in the cases with asbestosis than among the nonasbestosis cases. The number of malignant tumors related to asbestos exposure is expected to increase in the future.}, } @article {pmid11128876, year = {2000}, author = {Paoletti, L and Batisti, D and Bruno, C and Di Paola, M and Gianfagna, A and Mastrantonio, M and Nesti, M and Comba, P}, title = {Unusually high incidence of malignant pleural mesothelioma in a town of eastern Sicily: an epidemiological and environmental study.}, journal = {Archives of environmental health}, volume = {55}, number = {6}, pages = {392-398}, doi = {10.1080/00039890009604036}, pmid = {11128876}, issn = {0003-9896}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Confidence Intervals ; Environmental Monitoring ; Environmental Pollutants/*adverse effects ; Epidemiological Monitoring ; Female ; Humans ; Male ; Mesothelioma/*epidemiology/*etiology ; Middle Aged ; Mining ; Pleural Neoplasms/*epidemiology/*etiology ; Registries ; Risk Factors ; Sicily/epidemiology ; Survival Analysis ; }, abstract = {In a recent epidemiological study, researchers investigated mortality from malignant pleural neoplasms in Italy, and they detected some geographic clusters of cases of this disease. We found a town located in a volcanic area of eastern Sicily to be of special interest. The residents, some of whom were diagnosed with pleural mesothelioma, had never had any relevant exposure to asbestos during their professional lives. The results of an environmental survey suggested that a possible cause of asbestos exposure was the stone quarries near the town. The products of the quarries contain fibrous amphiboles, which are used widely in the local building industry. These fibrous amphiboles were identified as intermediate phases between tremolite and actinolite. Samples were collected from buildings in the town, and concentrations of amphibole fibers were evaluated. Fibrous phases were detected in 71% of the samples, and fiber concentrations ranged from a few thousand to more than 4 x 10(4) fibers/mg of material. In addition, we conducted a study on the mineral fiber lung burden in a pleural mesothelioma case. Many mineral fibers that were classified as the same tremolite-actinolite fibrous amphibole found in the quarries and in the building materials were detected in the lung tissue. The results suggest that the inhabitants of the town we studied had been exposed for several decades to asbestos fibers that were present in the material extracted from the local stone quarries. The material was subsequently used in the building industry, and this has caused an increased risk of pleural mesothelioma in the area.}, } @article {pmid11126482, year = {2000}, author = {Kuku, O and Parker, DL}, title = {Diagnosis and management of asbestosis.}, journal = {Minnesota medicine}, volume = {83}, number = {11}, pages = {47-49}, pmid = {11126482}, issn = {0026-556X}, mesh = {Asbestosis/*diagnosis/therapy ; Humans ; Lung Neoplasms/diagnosis ; Mesothelioma/diagnosis ; Pleural Neoplasms/diagnosis ; Prognosis ; }, abstract = {Asbestos-related illness usually arises at least 10 to 20 years after initial exposure. In many instances, patients may be unaware of the source of exposure. Although community-based exposures are unusual, recent events indicate that both communities and workers may have had significant exposure to asbestos contained within vermiculite. Physicians should obtain a medical history as outlined above when examining workers or community members who believe they have been significantly exposed to vermiculite. In addition, pulmonary function testing and chest radiographs should be obtained. If these are normal and there is no ongoing exposure, it is likely that no further evaluation is required. Physicians should have a radiologist familiar with occupational lung diseases read films. Patients may ask that a "B" reader, a physician who is certified by the National Institute for Occupational Safety and Health to read x-rays for changes related to the pneumoconioses, review their films. Facilitating smoking cessation and providing routine immunizations are important secondary preventive measures. Workers exposed to asbestos should receive ongoing screening as specified by the Occupational Safety and Health Administration. Over the last several decades, numerous epidemiologic studies have evaluated the efficacy of lung cancer screening. Period chest radiographs and sputum cytology have not been shown to increase lung cancer survival rates. Recent studies have demonstrated the potential benefit of scanning in the early detection of lung cancer. Although encouraging, these studies do not yet support the use of imaging for the routine screening of high-risk populations as required by the Occupational Safety and Health Administration.}, } @article {pmid11124644, year = {2000}, author = {Senyiğit, A and Bayram, H and Babayiğit, C and Topçu, F and Balci, AE and Satici, O}, title = {Comparison of the effectiveness of some pleural sclerosing agents used for control of effusions in malignant pleural mesothelioma: a review of 117 cases.}, journal = {Respiration; international review of thoracic diseases}, volume = {67}, number = {6}, pages = {623-629}, doi = {10.1159/000056291}, pmid = {11124644}, issn = {0025-7931}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Chest Tubes/adverse effects ; Environmental Exposure/adverse effects ; Female ; Humans ; Male ; Mechlorethamine/*administration & dosage ; Mesothelioma/etiology/mortality/pathology/*therapy ; Middle Aged ; Neoplasm Staging ; Oxytetracycline/*administration & dosage ; Pleural Effusion, Malignant/etiology/mortality/pathology/*therapy ; *Pleurodesis/methods ; *Propionibacterium acnes ; Sclerosing Solutions/*administration & dosage/adverse effects ; Survival Analysis ; Thoracostomy ; Treatment Outcome ; Turkey/epidemiology ; }, abstract = {BACKGROUND AND OBJECTIVES: Management of malignant pleural mesothelioma (MPM) has been an important clinical issue regardless of the treatment modality employed. We aimed to investigate the efficacy of oxytetracycline (OT), Corynebacterium parvum (CP), and nitrogen mustard (NM) in the management of pleural effusion associated with MPM.

METHODS: One hundred and seventeen patients who had stage-2 MPM or over according to the Butchart staging system and unilateral or bilateral pleural effusion took part in the study. The patients received either OT (35 mg/kg), CP (7 mg), or NM (0.4 mg/kg) through a chest tube for pleurodesis. The association between several clinical parameters and patient survival was also investigated.

RESULTS: OT was applied to 59, CP to 29 and NM to 29 cases. A statistical analysis of the results obtained by these agents have demonstrated that OT (30 days, 81%; 90 days, 76.2%) and CP (30 days, 86.2%; 90 days, 79.3%) led to a significantly higher rate of successful pleurodesis as compared to NM (30 days, 48.2%; 90 days, 41.3%; p <0.05). Although the procedure was generally well tolerated by the patients, the NM-treated group experienced significantly more nausea-vomiting (46.1%) and hypotension (35.8%) compared to patients who received OT (nausea-vomiting and hypotension 4.3%; p < 0.001) and CP (nausea-vomiting and hypotension 5.1%; p < 0.001). Furthermore, we found that thrombocytosis, chest pain and weight loss were significantly associated with poor prognosis, whereas epithelial type had a positive effect on survival.

CONCLUSION: These results suggest that OT and CP may be used as effective sclerosing agents for pleurodesis in the control of pleural effusions associated with MPM, without major side effects.}, } @article {pmid11124643, year = {2000}, author = {Senyiğit, A and Bayram, H and Babayiğit, C and Topçu, F and Nazaroğlu, H and Bilici, A and Leblebici, IH}, title = {Malignant pleural mesothelioma caused by environmental exposure to asbestos in the Southeast of Turkey: CT findings in 117 patients.}, journal = {Respiration; international review of thoracic diseases}, volume = {67}, number = {6}, pages = {615-622}, doi = {10.1159/000056290}, pmid = {11124643}, issn = {0025-7931}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Carcinogens/*adverse effects ; Environmental Exposure/*adverse effects ; Female ; Humans ; Male ; Mesothelioma/*diagnostic imaging/epidemiology/etiology/pathology ; Middle Aged ; Pleural Neoplasms/*diagnostic imaging/epidemiology/etiology/pathology ; Retrospective Studies ; Time Factors ; *Tomography, X-Ray Computed ; Turkey/epidemiology ; }, abstract = {BACKGROUND AND OBJECTIVES: Malignant pleural mesothelioma (MPM) is reported to be common in the southeast of Turkey, as a result of environmental asbestos exposure. The aim of this study was to evaluate the computed tomography (CT) features of MPM in patients with a history of asbestos exposure.

METHODS: The CT scans of 117 patients who had a diagnosis of MPM were retrospectively evaluated. Additionally, CT findings of histologic subtypes were compared.

RESULTS: The most common CT findings included pleural effusion (n = 104, 89%), pleural thickening (n = 96, 82%), mediastinal pleural involvement (n = 77, 66%) and interlobar fissural involvement (n = 62, 53%). Histologic subtype analysis was performed in 89 patients; of these, epithelial, sarcomatous and mixed types were identified in 46, 23 and 20 patients, respectively. An analysis of CT findings demonstrated that the involvement of mediastinal pleural (91%), interlobar fissure (87%) and lung parenchyma (48%) was significantly more frequent in sarcomatous type, as compared to epithelial (61% and p < 0.01; 35 and 4%, p < 0.0001, respectively) and mixed types (65% and p < 0.05; 10% and p < 0.0001; 10% and p < 0.01, respectively). Furthermore, there was a significant correlation between pericardial involvement and chest wall involvement (r = 0.42, p < 0.05) in sarcomatous type. Similarly, lymphadenopathy and parenchymal involvement (r = 0.23, p < 0.02), pericardial and chest wall involvement (r = 0.25, p < 0.01), chest wall and interlobar fissural involvement (r = 0.25, p < 0.01) were significantly correlated, when CT findings of all histologic subtypes were combined.

CONCLUSIONS: These results suggest that although CT findings of MPM vary, they may provide valuable clues to the diagnosis, at least in patients with a history of asbestos exposure. In addition, the presence of extensive lesions may suggest MPM of sarcomatous subtype.}, } @article {pmid11124642, year = {2000}, author = {Senyiğit, A and Babayiğit, C and Gökirmak, M and Topçu, F and Asan, E and Coşkunsel, M and Işik, R and Ertem, M}, title = {Incidence of malignant pleural mesothelioma due to environmental asbestos fiber exposure in the southeast of Turkey.}, journal = {Respiration; international review of thoracic diseases}, volume = {67}, number = {6}, pages = {610-614}, doi = {10.1159/000056289}, pmid = {11124642}, issn = {0025-7931}, mesh = {Adult ; Age Distribution ; Aged ; Asbestos/*adverse effects/analysis ; Carcinogens/*adverse effects/analysis ; Environmental Exposure/*adverse effects ; Female ; Humans ; Incidence ; Male ; Mesothelioma/diagnostic imaging/*epidemiology/*etiology ; Middle Aged ; Pleural Neoplasms/diagnostic imaging/*epidemiology/*etiology ; Radiography ; Time Factors ; Turkey/epidemiology ; }, abstract = {BACKGROUND: Inhabitants of the southeast of Turkey (ST) have been exposed since childhood to inhalation of asbestos, from a material containing tremolite, used for whitewashing. This has resulted in an increased incidence of malignant pleural mesothelioma (MPM).

OBJECTIVES: To review the epidemiological features of MPM cases in ST; to calculate and compare the incidence with the previously reported ones.

SUBJECTS AND METHODS: The study included 176 MPM cases from different places in ST. The incidence of MPM was calculated for those places according to the distribution of the cases.

RESULTS: In the previously identified regions of asbestos (region 1) where the population had been informed of the danger with the soil some decades ago, the MPM incidence was decreased, as compared to the previous reports. The annual incidence of MPM in these places was found to be 42.9 per million in this study while it had been reported to be 105.5 per million in the previous studies. In contrast, the incidence that was reported previously to be 2.75 per million in the regions where asbestos exposure had not been identified before (region 2) was found to be 8.6 per million in this study. In region 2 the incidence of MPM increased even in the second half of the last decade (5.9 versus 11.9 per million).

CONCLUSIONS: Use of asbestos-containing soil continues in different places in ST. Even if the use of this soil is abandoned today, MPM will be an important health problem in this region till the third or fourth decades of this century. Informing the villagers of the danger and preventing the use of this soil may result in a considerable decrease in the incidence of MPM.}, } @article {pmid11109564, year = {2000}, author = {Voss, B and Kerenyi, T and Müller, KM and Wilhelm, M}, title = {Scanning electron microscopical investigations of broncho-alveolar casts after intratracheal asbestos fibre instillation.}, journal = {International journal of hygiene and environmental health}, volume = {203}, number = {2}, pages = {127-134}, doi = {10.1078/S1438-4639(04)70017-6}, pmid = {11109564}, issn = {1438-4639}, mesh = {Animals ; Asbestos, Crocidolite/*toxicity ; Bronchoalveolar Lavage Fluid/*chemistry ; Disease Models, Animal ; Lung/*pathology/ultrastructure ; Male ; Microscopy, Electron, Scanning ; Mineral Fibers/toxicity ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Specific Pathogen-Free Organisms ; Trachea/*pathology/ultrastructure ; }, abstract = {The evaluation of the toxicity of mineral fibres has been tried to achieve in experimental animal models. However, the appearance of fibres in the pleural space could not be explained satisfactorily. Histomorphological examinations showed that intratracheal instillation of asbestos fibres leads to parabronchial and intraalveolar granulomatous tissue reactions and bronchial epithelial regenerations. For further elucidation of the pathogenesis of lung cancer and of mesothelioma the localisation and transport of inhaled fibres is of high interest. Thus, a three dimensional visualization of the structure of rat lungs before and after intratracheal instillation of UICC crocidolite fibres was performed by plastic casts to follow the way of asbestos fibres in the lung tissues and the pleura. The casts allowed to demonstrate airway structures with imprints of epithelial cells and blood vessels of normal and treated animals by scanning electron microscopy. Instilled asbestos fibres transformed bronchial structures and resulted in cystic deformations of the pleural surface. The penetration of single fibres through bronchial trunks and the visceral pleura could be shown for the first time in a three-dimensional topography of the affected tissue. Now, there is support for similar results of histomorphological examinations indicating the possibility that asbestos fibres could penetrate the pleura and migrate into the pleural space. The question if the migration of fibres is a mechanical movement or an active transport is still under discussion.}, } @article {pmid11108782, year = {2000}, author = {Hodgson, JT and Darnton, A}, title = {The quantitative risks of mesothelioma and lung cancer in relation to asbestos exposure.}, journal = {The Annals of occupational hygiene}, volume = {44}, number = {8}, pages = {565-601}, pmid = {11108782}, issn = {0003-4878}, mesh = {Asbestos/*adverse effects ; Asbestos, Amphibole/adverse effects ; Asbestos, Serpentine/adverse effects ; Cohort Studies ; Female ; Humans ; Lung Neoplasms/etiology/*mortality ; Male ; Mesothelioma/etiology/*mortality ; Mineral Fibers/adverse effects ; Occupational Exposure/*adverse effects/analysis ; Peritoneal Neoplasms/mortality ; Pleural Neoplasms/mortality ; Regression Analysis ; Risk ; *Risk Assessment ; Smoking/adverse effects ; }, abstract = {Mortality reports on asbestos exposed cohorts which gave information on exposure levels from which (as a minimum) a cohort average cumulative exposure could be estimated were reviewed. At exposure levels seen in occupational cohorts it is concluded that the exposure specific risk of mesothelioma from the three principal commercial asbestos types is broadly in the ratio 1:100:500 for chrysotile, amosite and crocidolite respectively. For lung cancer the conclusions are less clear cut. Cohorts exposed only to crocidolite or amosite record similar exposure specific risk levels (around 5% excess lung cancer per f/ml.yr); but chrysotile exposed cohorts show a less consistent picture, with a clear discrepancy between the mortality experience of a cohort of xhrysotile textile workers in Carolina and the Quebec miners cohort. Taking account of the excess risk recorded by cohorts with mixed fibre exposures (generally<1%), the Carolina experience looks uptypically high. It is suggested that a best estimate lung cancer risk for chrysotile alone would be 0.1%, with a highest reasonable estimate of 0.5%. The risk differential between chrysotile and the two amphibole fibres for lunc cancer is thus between 1:10 and 1:50. Examination of the inter-study dose response relationship for the amphibole fibres suggests a non-linear relationship for all three cancer endpoints (pleural and peritoneal mesotheliomas, and lung cancer). The peritoneal mesothelioma risk is proportional to the square of cumulative exposure, lung cancer risk lies between a linear and square relationship and pleural mesothelioma seems to rise less than linearly with cumulative dose. Although these non-linear relationships provide a best fit ot the data, statistical and other uncertainties mean that a linear relationship remains arguable for pleural and lung tumours (but not or peritoneal tumours). Based on these considerations, and a discussion fo the associated uncertainties, a series of quantified risk summary statements for different elvels of cumulative exposure are presented.}, } @article {pmid11107225, year = {2001}, author = {Alexander, DL}, title = {School employees: the forgotten municipal workers.}, journal = {Occupational medicine (Philadelphia, Pa.)}, volume = {16}, number = {1}, pages = {65-78}, pmid = {11107225}, issn = {0885-114X}, mesh = {Accidents, Occupational/*statistics & numerical data ; Humans ; Noise, Occupational/statistics & numerical data ; Occupational Diseases/epidemiology ; Occupational Exposure/*statistics & numerical data ; Occupational Health/*statistics & numerical data ; Risk Management ; *Schools/statistics & numerical data ; United States ; Violence/statistics & numerical data ; Workforce ; }, abstract = {The occupational health and safety issues of public school employees in large urban areas are many and complex. Crumbling school infrastructure and crowded classrooms are associated with inadequate indoor air quality, asbestos exposure, noisy environments, and enhanced transmission of communicable and infectious diseases. Poor ventilation in vocational education classrooms, duplicator rooms, kitchens, and science laboratories may also contribute to hazardous exposures. Ergonomic hazards may be responsible for increasing rates of musculoskeletal disorders. Other work-related illnesses and injuries now documented among school employees include asthma, mesothelioma, asbestos-related lung cancer, violent assault, voice disorders, and depression. Such a diverse industry with many potentially hazardous activities and conditions calls for a comprehensive research and intervention agenda.}, } @article {pmid11103845, year = {2000}, author = {Tossavainen, A}, title = {International expert meeting on new advances in the radiology and screening of asbestos-related diseases.}, journal = {Scandinavian journal of work, environment & health}, volume = {26}, number = {5}, pages = {449-454}, pmid = {11103845}, issn = {0355-3140}, mesh = {Adult ; Aged ; Aged, 80 and over ; Algorithms ; Asbestosis/complications/*diagnosis/diagnostic imaging ; Female ; Humans ; Incidence ; Lung Neoplasms/*diagnosis/diagnostic imaging/etiology ; Male ; Mass Screening ; Mesothelioma/*diagnosis/diagnostic imaging/etiology ; Middle Aged ; *Occupational Exposure ; Pleural Neoplasms/*diagnosis/diagnostic imaging/etiology ; Predictive Value of Tests ; Radiography, Thoracic ; Risk Factors ; Sensitivity and Specificity ; Smoking/adverse effects ; Smoking Cessation ; Smoking Prevention ; Time Factors ; *Tomography, X-Ray Computed/methods ; }, } @article {pmid11102295, year = {2000}, author = {Zeren, EH and Gümürdülü, D and Roggli, VL and Zorludemir, S and Erkişi, M and Tuncer, I}, title = {Environmental malignant mesothelioma in southern Anatolia: a study of fifty cases.}, journal = {Environmental health perspectives}, volume = {108}, number = {11}, pages = {1047-1050}, pmid = {11102295}, issn = {0091-6765}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Carcinogens, Environmental/adverse effects ; Environmental Exposure ; Environmental Health ; Female ; Humans ; Lung Neoplasms/*etiology/pathology ; Male ; Mesothelioma/*etiology/pathology ; Middle Aged ; Turkey ; }, abstract = {Malignant mesothelioma is a highly aggressive tumor of the serous membranes, which in humans results from exposure to asbestos and asbestiform fibers. Although occupational malignant mesothelioma is still the most common form of this lesion, naturally contaminated soil can play an important role in the development of environmental malignant mesothelioma in some parts of the world. Fifty cases of malignant mesothelioma (MM) from southern Turkey with no occupational history of asbestos exposure were reviewed regarding pathologic and clinical features. A case of hyaline fibrous plaque of the pleura was also included in this series. Histologically the cases were classified as epithelial (36 cases); sarcomatous (7 cases); and biphasic (7 cases). One of the sarcomatous cases was desmoplastic. Ultrastructural examination of the tumor tissue in three cases revealed long-surface microvilli in epithelial cells. Interstitial cells of the lung in one case showed electron-dense asbestos fibers in the cytoplasm. Mineralogical analyses of the lung tissue in three cases of MM and the case of pleural plaque showed high amounts of asbestos fibers most consistent with tremolite and actinolite. The clinical and pathologic features of our cases support that the environmental inhalation of asbestos is still a major health problem in some parts of Turkey.}, } @article {pmid11100950, year = {2000}, author = {Mándi, A and Posgay, M and Vadász, P and Major, K and Rödelsperger, K and Tossavainen, A and Ungváry, G and Woitowitz, HJ and Galambos, E and Németh, L and Soltész, I and Egerváry, M and Böszörményi Nagy, G}, title = {Role of occupational asbestos exposure in Hungarian lung cancer patients.}, journal = {International archives of occupational and environmental health}, volume = {73}, number = {8}, pages = {555-560}, doi = {10.1007/s004200000172}, pmid = {11100950}, issn = {0340-0131}, mesh = {Adolescent ; Adult ; Asbestos/*adverse effects ; Data Collection ; Female ; Humans ; Hungary ; Lung Neoplasms/*etiology ; Male ; Mesothelioma/*etiology ; Middle Aged ; *Occupational Diseases/etiology ; *Occupational Exposure ; Occupations ; Pleural Neoplasms/*etiology ; Retrospective Studies ; Smoking/adverse effects ; Surveys and Questionnaires ; Time Factors ; }, abstract = {OBJECTIVE: What is the frequency of occupational asbestos exposure among patients suffering from malignant respiratory tumours and how many of these tumours are associated with asbestos in Hungary?

METHODS: An internationally established questionnaire with 29 questions, covering the most characteristic activities of asbestos exposure at the workplace was completed for 300 patients with respiratory malignancies, i.e. 297 patients with lung cancer and three with mesothelioma of the pleura. From the questionnaire, the smoking habits were estimated and cumulative asbestos exposure was assessed in fibre-years. Additionally, lung X-rays were classified and the national data on the incidence of malignant pleura mesothelioma were analysed.

RESULTS: A cumulative asbestos exposure of 25 fibre-years or more was detected in 11 patients with lung cancer (4%) and in each of the three patients with pleural mesothelioma (100%). In a further 72 patients (24%), cumulative occupational asbestos exposure was assessed as below 25 fibre-years (between 0.01 and 23.9 fibre-years). In this group, car and truck mechanics, and installation and construction workers using asbestos-cement were registered. Among patients with an asbestos exposure of 25 fibre-years or more, six asbestos-cement production workers were observed, among them the three mesothelioma cases. A weak but significant association between positive X-ray findings and exposure estimates could be demonstrated. Additionally, results of the lung tissue fibre counts by scanning transmission electron microscopy were available for 25 of the lung cancer patients. A good correlation was observed between the asbestos fibre counts and the assessment of cumulative asbestos exposure. In Hungary, 84 cases of pleural mesothelioma were registered in 1997 and 73 in 1998. These numbers correspond to an annual incidence of about one new case per 100,000 inhabitants older than 15 years.

CONCLUSIONS: The annual incidence of lung cancer in Hungary is about 6,000. Since in our series of lung cancer patients about 4% were observed, which could be accepted as representing occupational disease because of a cumulative exposure to 25 fibre-years or more, the annual asbestos related lung tumour incidences may be estimated to be approximately 150 or more. The proportion of nearly two estimated cases of lung cancer per case of pleural mesothelioma corresponds to international experience. Up to now, lung cancer cases only exceptionally have been registered as occupational diseases, i.e. they were seriously under-diagnosed in Hungary. For improving this situation, diagnostic assistance by a self-interview with a questionnaire covering the working history for all newly diagnosed lung cancer patients would be helpful.}, } @article {pmid11091251, year = {2000}, author = {Sebbag, G and Yan, H and Shmookler, BM and Chang, D and Sugarbaker, PH}, title = {Results of treatment of 33 patients with peritoneal mesothelioma.}, journal = {The British journal of surgery}, volume = {87}, number = {11}, pages = {1587-1593}, doi = {10.1046/j.1365-2168.2000.01571.x}, pmid = {11091251}, issn = {0007-1323}, mesh = {Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Male ; Mesothelioma/drug therapy/pathology/*surgery ; Middle Aged ; Peritoneal Neoplasms/drug therapy/pathology/*surgery ; Prognosis ; Retrospective Studies ; Survival Analysis ; }, abstract = {BACKGROUND: Peritoneal mesothelioma is a rare peritoneal malignancy, representing approximately one-third of all mesotheliomas. It is regarded as a universally fatal cancer with few treatment options.

METHODS: Records of 33 patients with peritoneal mesothelioma were reviewed retrospectively. Demographic, clinical and quantitative prognostic indicators were evaluated and analysed statistically using survival as endpoint. Patients were treated by a uniform strategy involving cytoreductive surgery with peritonectomy procedures and perioperative intraperitoneal chemotherapy (cisplatin, doxorubicin).

RESULTS: There were ten women and 23 men; mean age was 53.0 years. Asbestos exposure was recorded in five patients and a family history of cancer in 13. Presentation was mainly abdominal distension and pain. Median survival was 31.0 months; overall projected survival at 3 years was 56 per cent. The most significant positive predictive factors of survival were: female sex (P= 0.003), low prior surgical score (P=0.002), completeness of cytoreduction (P=0.0002) and second-look surgery (P=0.019). The morbidity rate for this combined treatment was 33 per cent and the perioperative mortality rate was 3 per cent.

CONCLUSION: Although peritoneal mesothelioma is rare, progress in its management has occurred. Survival has been extended and selection factors by which patients may be allocated to aggressive management strategies have been defined.}, } @article {pmid11065243, year = {2000}, author = {Sato, F and Yamazaki, H and Ataka, K and Mashima, I and Suzuki, K and Takahashi, T and Umezu, H and Gejyo, F}, title = {Malignant peritoneal mesothelioma associated with deep vein thrombosis following radiotherapy for seminoma of the testis.}, journal = {Internal medicine (Tokyo, Japan)}, volume = {39}, number = {11}, pages = {920-924}, doi = {10.2169/internalmedicine.39.920}, pmid = {11065243}, issn = {0918-2918}, mesh = {Humans ; Male ; Mesothelioma/*complications/diagnosis ; Middle Aged ; Peritoneal Neoplasms/*complications/diagnosis ; Radiotherapy/adverse effects ; Seminoma/*radiotherapy ; Testicular Neoplasms/diagnosis/*radiotherapy ; Venous Thrombosis/*etiology ; }, abstract = {A 52-year-old man developed malignant peritoneal mesothelioma 17 years after radiotherapy for seminoma of the testis. Although asbestos exposure is considered to be the major risk factor for the development of malignant mesothelioma, prior therapeutic radiation has also been postulated as a causative factor. The unexplained appearance of ascites or pleural effusion within a previously irradiated area should be considered suggestive of malignant mesothelioma in any long-term survivor of cancer. In addition, the patient suffered a deep vein thrombosis four years before the diagnosis of mesothelioma. Deep vein thrombosis is a common complication of malignant disease, and is often the first clue to occult malignancy.}, } @article {pmid11045063, year = {1999}, author = {Hashim, S and Abdullah, BJ and Jayaram, G}, title = {MRI appearances of peritoneal mesothelioma--a case report.}, journal = {The Medical journal of Malaysia}, volume = {54}, number = {3}, pages = {358-360}, pmid = {11045063}, issn = {0300-5283}, mesh = {Aged ; Fatal Outcome ; Humans ; *Magnetic Resonance Imaging ; Male ; Mesothelioma/*diagnosis ; Peritoneal Neoplasms/*diagnosis ; }, abstract = {A rare case of diffuse malignant peritoneal mesothelioma in a 71 year-old Malay man with no previous history of asbestos or radiation exposure is described. The clinical manifestation was a large abdominal mass. At laparotomy he was found to be in the advanced stage of the disease. The tumour was not resectable and patient was sent home. He gradually deteriorated and died three months after diagnosis was made. The magnetic resonance imaging (MRI) features of peritoneal mesothelioma which has not been previously reported are described.}, } @article {pmid11037344, year = {2000}, author = {Krismann, M and Adams, H and Jaworska, M and Müller, KM and Johnen, G}, title = {Patterns of chromosomal imbalances in benign solitary fibrous tumours of the pleura.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {437}, number = {3}, pages = {248-255}, doi = {10.1007/s004280000235}, pmid = {11037344}, issn = {0945-6317}, mesh = {Aged ; Aged, 80 and over ; *Chromosome Aberrations ; Female ; Humans ; Immunohistochemistry ; Male ; Mesothelioma/genetics ; Middle Aged ; Nucleic Acid Hybridization ; Pleural Neoplasms/*genetics ; }, abstract = {Solitary fibrous tumours (SFTs) of the pleura, in contrast to malignant mesothelioma, occur independently of previous asbestos exposure. They are benign tumours, but may recur if the stalk to the adjacent pleural or lung tissue remains in situ during surgical removal. The molecular pathology of SFTs is largely unknown. We used comparative genomic hybridisation (CGH) to characterise 12 localised SFTs and 12 predominantly sarcomatoid mesotheliomas. Fifty-eight percent of the investigated SFTs did not show any chromosomal imbalances. The most frequent defects were losses on chromosome arms 13q (33%), 4q and 21q (17% each). Significant gains were seen at chromosome 8 and at 15q in two cases each. There was no correlation between tumour size and molecular pathology findings. In contrast, 75% of the mesotheliomas carried chromosomal defects. On average, the mesotheliomas showed over three times as many defects per tumour as the SFTs. Localisation of several frequent losses and gains were similar to those of the SFTs. Therefore, in individual cases, a clear distinction between SFTs and sarcomatoid mesotheliomas is not possible based on CGH analysis alone. Further molecular characterisation of this rare tumour entity will be necessary to elucidate possible genes involved in early tumorigenesis.}, } @article {pmid11036518, year = {2000}, author = {Ruffié, P}, title = {[Management of patients with malignant mesothelioma of the pleura].}, journal = {Presse medicale (Paris, France : 1983)}, volume = {29}, number = {25}, pages = {1413-1416}, pmid = {11036518}, issn = {0755-4982}, mesh = {Adult ; Age Factors ; Asbestos/*adverse effects ; Female ; France/epidemiology ; Humans ; Male ; *Mesothelioma/epidemiology/therapy ; Middle Aged ; Occupational Diseases/*etiology/prevention & control ; *Pleural Neoplasms/epidemiology/therapy ; Prognosis ; Risk Factors ; Sex Factors ; }, } @article {pmid11025463, year = {2000}, author = {Piazza, D and Caruso, F and Scaringi, S and Ferrara, M and Latteri, F and Dell'Erba, D}, title = {Primary diffuse malignant peritoneal mesothelioma: case report and update of therapy.}, journal = {Journal of surgical oncology}, volume = {75}, number = {1}, pages = {55-58}, doi = {10.1002/1096-9098(200009)75:1<55::aid-jso10>3.0.co;2-d}, pmid = {11025463}, issn = {0022-4790}, mesh = {Female ; Humans ; Ileostomy ; Laparotomy ; *Mesothelioma/diagnosis/pathology/surgery ; Middle Aged ; *Peritoneal Neoplasms/diagnosis/pathology/surgery ; }, abstract = {BACKGROUND AND OBJECTIVES: Primary Diffuse Malignant Peritoneal Mesothelioma is a rare disease, with an incidence of 2.2 cases in 1. 000.000 in the USA. It occupies 10% of all mesotheliomas referred in literature.

METHODS: We describe a case of diffuse malignant peritoneal mesothelioma arising in a 54-year-old woman who presented a small bowel occlusion. A middle line laparotomy was done; multiple biopsies and an ileostomy were performed. There was not a history of exposure to asbestos. Histologic diagnosis was based on light microscopy, histochemistry, and immunohistochemistry.

RESULTS: Patient had no further treatment because of her poor general conditions. She died 4 months later.

CONCLUSIONS: Update of treatment is briefly described with particular attention to multimodality approach (surgery, chemotherapy, radiotherapy) and other new therapeutic options (iperthermochemotherapy, immunotherapy, gene therapy), currently in clinical trials.}, } @article {pmid11024203, year = {2000}, author = {Berry, G and Newhouse, ML and Wagner, JC}, title = {Mortality from all cancers of asbestos factory workers in east London 1933-80.}, journal = {Occupational and environmental medicine}, volume = {57}, number = {11}, pages = {782-785}, pmid = {11024203}, issn = {1351-0711}, mesh = {Asbestos/*adverse effects ; Carcinogens/*adverse effects ; Cause of Death ; Chi-Square Distribution ; Female ; Follow-Up Studies ; Humans ; London/epidemiology ; Lung Neoplasms/etiology/mortality ; Male ; Mesothelioma/etiology/mortality ; Neoplasms/etiology/*mortality ; Occupational Diseases/etiology/mortality ; Occupational Exposure/adverse effects/statistics & numerical data ; Peritoneal Neoplasms/etiology/mortality ; Pleural Neoplasms/etiology/mortality ; }, abstract = {OBJECTIVE: To give the observed and expected deaths due to cancer at all separate sites in asbestos workers in east London, and to analyse these for overall effect and exposure-response trend.

METHODS: The mortality experience of a cohort of over 5000 men and women followed up for over 30 years since first exposure to asbestos has been extracted.

RESULTS: There was a large excess of deaths due to cancer (537 observed, 222 expected). Most of these were due to cancer of the lung (232 observed, 77 expected) and pleural (52) and peritoneal (48) mesothelioma. The exposure-response trend for all these three causes was highly significant. There was also an excess of cancer of the colon (27 observed, 15 expected) which was significantly related to exposure. There were significant excesses of cancer of the ovary, of the liver, and of the oesophagus but with no consistent relation to exposure.

CONCLUSIONS: The excess risk of cancer after exposure to asbestos was mainly due to cancer of the lung and mesothelioma. An exposure related excess of cancer of the colon was also detected but the possibility that some of these deaths may have been peritoneal mesotheliomas could not be excluded. There was no consistent evidence of exposure related excesses at any other site.}, } @article {pmid11023443, year = {2000}, author = {Howie, RM}, title = {An important source of error in asbestos-related lung cancer estimates.}, journal = {The Annals of occupational hygiene}, volume = {44}, number = {6}, pages = {484-487}, pmid = {11023443}, issn = {0003-4878}, mesh = {Asbestos/*adverse effects ; Bias ; *Data Interpretation, Statistical ; Humans ; Lung Neoplasms/*chemically induced/*epidemiology ; Mesothelioma/chemically induced/epidemiology ; Occupational Diseases/*chemically induced/*epidemiology ; *Registries ; Smoking/adverse effects ; United Kingdom/epidemiology ; }, } @article {pmid11013806, year = {2000}, author = {Krismann, M and Müller, KM}, title = {[Malignant mesothelioma of the pleura, pericardium and peritoneum. 1: Etiology, pathogenesis, pathology].}, journal = {Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen}, volume = {71}, number = {8}, pages = {877-886}, doi = {10.1007/s001040051151}, pmid = {11013806}, issn = {0009-4722}, mesh = {Animals ; Asbestosis/complications/genetics/pathology ; Cell Transformation, Neoplastic/genetics/pathology ; Chromosome Aberrations/genetics ; Heart Neoplasms/etiology/genetics/*pathology ; Humans ; Mesothelioma/etiology/genetics/*pathology ; Pericardium/*pathology ; Peritoneal Neoplasms/etiology/genetics/*pathology ; Peritoneum/pathology ; Pleura/pathology ; Pleural Neoplasms/etiology/genetics/*pathology ; }, abstract = {The incidence of primary malignant neoplasms of the pleura, the pericardium and the peritoneum in Germany has been rising since about the mid-1980s. A continuing rise is expected until about 2020, predominantly due to the peak of asbestos processing in Germany between 1965 and 1980. About 90% of the mesotheliomas stored in the files of the German Mesothelioma Registry in Bochum are asbestos related and therefore possibly due to occupational exposure that may be compensated by the professional associations. More than 500 mesotheliomas annually can be diagnosed in the German Mesothelioma Registry. In this first part of the series on mesotheliomas, current concepts on etiology and pathogenesis as well as diagnostic procedures and standards are discussed. At the present, specific chromosomal or genetic defects that constantly give rise to a mesothelioma are not known. The initiation and progression of malignant mesotheliomas is a highly complex mechanism that is based on individual genetic alterations. A reliable diagnosis is the basis for therapeutic, prognostic and medicolegal consequences; in general, it can be achieved by thoracoscopic inspection with selected biopsy. Surgery may gain a more important role in the therapy of malignant tumors of serosal membranes not only in palliative, but also in potential curative approaches if the diagnosis can be made at earlier tumor stages.}, } @article {pmid11002475, year = {2000}, author = {Woźniak, H and Wiecek, E}, title = {[Chrysotile asbestos: biological effects, the work environment highest allowable concentration and neoplasm risk].}, journal = {Medycyna pracy}, volume = {51}, number = {3}, pages = {285-297}, pmid = {11002475}, issn = {0465-5893}, mesh = {Asbestos/*adverse effects/*analysis ; Asbestos, Serpentine/*adverse effects/*analysis ; Humans ; Neoplasms/*etiology ; Occupational Exposure/*adverse effects ; Reference Values ; Risk Factors ; Time Factors ; }, abstract = {The authors present the most essential data on physical and chemical properties of chrysotile, sources of its emission, the extent of occupational exposure, and biological effect, used in setting MAC values for chrysotile-containing dusts. Exploitable asbestos deposits do not exist in Poland, but admixtures of asbestos minerals have been found in some deposits of mineral raw materials located in the area of Lower Silesia (melafir, gabbro, dolomite. ore, nickel, magnesite, serpentinite). In the 1970s, about 100,000 tonnes of asbestos, containing 90% of chrysotile, were used annually in Poland. This figure decreased to 30,000 tonnes in 1991. In 1985 the use of crocidolite asbestos was stopped, and in 1999, the use of asbestos-containing products was banned by the virtue of the legal act. At present, the Minister of Economy in agreement with the Minister of Environmental Protection sets regularly the list of asbestos-containing products permitted for the production or in the customs area. Nowadays, the range of dust concentrations in plants which use asbestos products amounts to 0.1-0.6 mg/m3 for total dust and 0.002-0.07 f/cm3 for respirable mineral fibres; and during exploitation of rock raw material deposits 0.7-280 mg/m3, and 0.01-3.3 f/cm3, respectively. During the years 1976-96, 1520 cases of asbestos-related occupational diseases were diagnosed. This figure included 1314 cases of asbestosis, 154 cases of lung cancer and 52 cases of pleura mesothelioma. MAC values for chrysotile and chrysotile-containing dusts are: 0.2 f/cm3 and 1 mg/m3.}, } @article {pmid10997827, year = {2000}, author = {Bourdès, V and Boffetta, P and Pisani, P}, title = {Environmental exposure to asbestos and risk of pleural mesothelioma: review and meta-analysis.}, journal = {European journal of epidemiology}, volume = {16}, number = {5}, pages = {411-417}, pmid = {10997827}, issn = {0393-2990}, mesh = {Asbestos/*adverse effects ; Case-Control Studies ; Cohort Studies ; Confidence Intervals ; *Environmental Exposure ; Female ; Humans ; Male ; Mesothelioma/*epidemiology/etiology ; Meta-Analysis as Topic ; Pleural Neoplasms/*epidemiology/etiology ; Risk ; Risk Factors ; Rural Population ; Urban Population ; }, abstract = {A number of epidemiological studies have addressed the risk of pleural mesothelioma from environmental (household and neighborhood) exposure to asbestos, but no overall risk estimate is available. We reviewed the epidemiological studies on risk of pleural mesothelioma and household or neighborhood exposure to asbestos. We identified eight relevant studies; most were conducted in populations with relatively high exposure levels. We combined the risk estimates in a meta-analysis based on the random-effects model. The relative risks (RRs) of pleural mesothelioma for household exposure ranged between 4.0 and 23.7, and the summary risk estimate was 8.1 (95% confidence interval [CI]: 5.3-12). For neighborhood exposure, RRs ranged between 5.1 and 9.3 (with a single RR of 0.2) and the summary estimate was 7.0 (95% CI: 4.7-11). This review suggests a substantial increase in risk of pleural mesothelioma following high environmental exposure to asbestos; however, the available data are insufficient to estimate the magnitude of the excess risk at the levels of environmental exposure commonly encountered by the general population in industrial countries.}, } @article {pmid10992539, year = {2000}, author = {Attanoos, RL and Suvarna, SK and Rhead, E and Stephens, M and Locke, TJ and Sheppard, MN and Pooley, FD and Gibbs, AR}, title = {Malignant vascular tumours of the pleura in "asbestos" workers and endothelial differentiation in malignant mesothelioma.}, journal = {Thorax}, volume = {55}, number = {10}, pages = {860-863}, pmid = {10992539}, issn = {0040-6376}, mesh = {Adult ; Aged ; Antigens, CD34/analysis ; Asbestos/*adverse effects ; Carcinogens/*adverse effects ; Diagnosis, Differential ; Hemangioendothelioma, Epithelioid/*diagnosis/etiology ; Humans ; Male ; Mesothelioma/*diagnosis/etiology ; Microscopy, Electron/methods ; Middle Aged ; Platelet Endothelial Cell Adhesion Molecule-1/analysis ; Pleural Neoplasms/*diagnosis/etiology ; Vascular Neoplasms/*diagnosis/etiology ; von Willebrand Factor/chemistry ; }, abstract = {BACKGROUND: Three cases of diffuse malignant vascular tumours of the pleura are described which mimicked malignant mesothelioma clinically and pathologically (so called "pseudomesothelioma"). All had occupational histories of exposure to asbestos. The relationship of these tumours to mesothelioma and asbestos exposure is discussed.

METHODS: To examine the histogenetic relationship between mesothelioma and these three tumours an immunohistochemical analysis of vascular marker (CD31, CD34, and Von Willebrand factor) expression was undertaken in 92 cases of pleural mesothelioma, in addition to these three tumours. Electron microscopic fibre analysis of lung tissue was performed on each of the three cases to assess asbestos fibre content.

RESULTS: Diffuse pleural epithelioid haemangioendotheliomas may closely resemble malignant mesothelioma clinically and pathologically but, of the 92 pleural mesotheliomas tested, none showed expression of CD31, CD34, and Von Willebrand factor. Although all three cases had claimed exposure to asbestos, ferruginous bodies typical of asbestos were only seen by light microscopy in case 2, and only in this subject was the asbestos fibre content raised in comparison with the range seen in a non-exposed background population. The latent period in the pleural epithelioid haemangioendotheliomas ranged from 18 to 60 years.

CONCLUSIONS: Endothelial differentiation does not appear to occur in mesothelioma and therefore should be clearly separated from it. No definite association between pleural epithelioid haemangioendothelioma and exposure to asbestos can be made from this small series but further investigation is warranted.}, } @article {pmid10989371, year = {2000}, author = {Cullen, RT and Searl, A and Buchanan, D and Davis, JM and Miller, BG and Jones, AD}, title = {Pathogenicity of a special-purpose glass microfiber (E glass) relative to another glass microfiber and amosite asbestos.}, journal = {Inhalation toxicology}, volume = {12}, number = {10}, pages = {959-977}, doi = {10.1080/08958370050138012}, pmid = {10989371}, issn = {0895-8378}, mesh = {Administration, Inhalation ; Aerosols ; Animals ; Asbestos, Amosite/administration & dosage/pharmacokinetics/*toxicity ; Body Burden ; Carcinoma/etiology/mortality/pathology ; *Glass ; *Inhalation Exposure ; Injections, Intraperitoneal ; Lung/drug effects/metabolism/pathology ; Lung Neoplasms/etiology/mortality/pathology ; Male ; Mesothelioma/etiology/mortality/pathology ; Mineral Fibers ; Neoplasms, Experimental/etiology/mortality/pathology ; Particle Size ; Pulmonary Fibrosis/etiology/mortality/pathology ; Rats ; Rats, Wistar ; Survival Analysis ; Survival Rate ; Toxicity Tests ; }, abstract = {This article describes the activity of an E-glass microfiber (104E) during chronic inhalation and intraperitoneal injection studies in rats. Results are compared with another microfiber of similar dissolution rate (k(dis)), code 100/475, and the more durable amosite asbestos, both of which we had previously used in similar experiments (Davis et al., 1996). Rats were exposed to aerosol concentrations of 1000 fibers (longer than 5 microm)/ml, as measured by optical microscopy, for 7 h/day, 5 days/wk. Subgroups of rats were followed for mean lung burden, early and late signs of fibrosis, and tumor incidence. At the end of 12 mo of exposure, the mean number of 104E fibers of all lengths in the lungs was approximately double that for amosite but two-thirds of that for 100/475. For fibers longer than 15 microm, the mean 104E burden was similar to that for the amosite and more than twice that of the 100/475. After a 12-mo recovery period, the retained lung burdens (of fibers of all lengths) were approximately 30% of those at 12 mo for both microfibers, and somewhat higher (approximately 44%) for amosite. Amosite and 100/475 fibers longer than 15 microm were more persistent in the lungs than 104E fibers. The chemical composition of 104E fibers did not appear to have been significantly altered by up to 24 mo of residence in lung tissue, whereas the composition of 100/475 was substantially altered over the same time period. From the inhalation study, out of the pathology subgroup of 43 animals exposed to 104E microfibers, 10 had lung tumors (7 carcinoma, 3 adenoma) and 2 had mesotheliomas, whereas in 42 rats exposed to amosite asbestos, there were 16 lung tumors (7 carcinoma, 9 adenoma) and 2 mesotheliomas. The 104E- and amosite-treated animals had similar levels of fibrosis. In contrast, 38 animals treated with 100/475 had little fibrosis, 4 lung tumors (adenomas), and no mesotheliomas. The greater pathogenicity of the 104E fibers, compared to 100/475 fibers, might be partly explained by the greater numbers of long fibers retained in the lung after 12 mo of inhalation. However, we speculate that modification of surface properties by extensive selective leaching of some glass components reduces the toxic potential of 100/475. In a parallel intraperitoneal injection study, 104E caused considerably more mesotheliomas (21 rats out of 24) than 100/475 (8 rats out of 24). In addition, 104E appeared to be more active than amosite asbestos, since mesotheliomas appeared much more quickly in the 104E-treated animals. In conclusion, we have shown that two microfiber types, 100/475 and 104E, of similar dissolution rates, had markedly different pathogenicity in rats. We believe that this contrast is only partly due to differences in numbers of long fibers and that differences in surface properties of the fibers, possibly due to proportionately greater leaching of 100/475 fibers, play an important role.}, } @article {pmid10969653, year = {2000}, author = {Harrison, LH and Schwarzenberger, PO and Byrne, PS and Marrogi, AJ and Kolls, JK and McCarthy, KE}, title = {Gene-modified PA1-STK cells home to tumor sites in patients with malignant pleural mesothelioma.}, journal = {The Annals of thoracic surgery}, volume = {70}, number = {2}, pages = {407-411}, doi = {10.1016/s0003-4975(00)01557-5}, pmid = {10969653}, issn = {0003-4975}, mesh = {Female ; *Genetic Therapy ; Humans ; Mesothelioma/diagnostic imaging/pathology/*therapy ; Ovarian Neoplasms/genetics ; Pleural Neoplasms/diagnostic imaging/pathology/*therapy ; Radiopharmaceuticals ; Simplexvirus/*genetics ; Technetium Compounds ; Thymidine Kinase/*genetics ; Tomography, Emission-Computed, Single-Photon ; Transduction, Genetic ; Tumor Cells, Cultured ; }, abstract = {BACKGROUND: Malignant mesothelioma is an uncommon but lethal cancer of increasing incidence, particularly among patients with a history of exposure to asbestos. Although numerous treatments have been employed, including chemotherapy, radiation therapy, surgical resection, and combinations of the above, no satisfactory treatment yet exists, and affected patients will die of this disease, usually within 12 months. Gene-based therapies constitute a new approach that offers hope of improved control of these tumors while being associated with less morbidity than conventional chemotherapeutic or surgical regimens. We demonstrated that PA1-STK cells home in vivo to mesothelioma deposits, a phenomenon that is required for optimal exertion of this therapeutic concept.

METHODS: Gene-modified ovarian cancer cells expressing the thymidine-kinase gene (PA1-STK) were radiolabeled with 99Tc and infused into the pleural space of 4 patients with malignant pleural mesothelioma, then scanned to determine distribution of the cells.

RESULTS: PA1-STK cells recognized and adhered preferentially to mesothelioma lining the chest wall.

CONCLUSIONS: Cell-based "suicide gene" therapy utilizing the "bystander effect" with the gene-modified ovarian cancer cell line PA1-STK is feasible in human pleural mesothelioma. We have shown that this trafficking and homing of the therapeutic cells to the intrapleural tumor sites, a requirement for success with this novel therapeutic concept, is also valid in humans.}, } @article {pmid10968564, year = {2000}, author = {Järvholm, B}, title = {Natural organic fibers--health effects.}, journal = {International archives of occupational and environmental health}, volume = {73 Suppl}, number = {}, pages = {S69-74}, doi = {10.1007/pl00014629}, pmid = {10968564}, issn = {0340-0131}, mesh = {Cellulose/*adverse effects ; Dust/*adverse effects ; Female ; Humans ; Inhalation Exposure/adverse effects ; Male ; Mesothelioma/epidemiology/etiology ; Occupational Exposure/*adverse effects ; Respiratory Tract Diseases/epidemiology/*etiology ; Respiratory Tract Neoplasms/epidemiology/etiology ; Textiles/*adverse effects ; }, abstract = {OBJECTIVES: Natural organic fibers are used in large quantities in the production of paper products and textiles. They are also constituents of food and added to food to promote health. The objective of this review is to evaluate the health effects of natural organic fibers. The health effects of dietary fibers are excluded from the review.

METHODS: This is a literature review.

RESULTS: Exposure to these fibers in industry is usually not characterized as fibers but as dust. Rather dusty conditions have been reported in both paper and textile industries with concentrations up to and above 30 mg/m3. Both in the paper and textile industry inorganic fibers may occur making it hard to evaluate health effects of natural organic fibers from studies of workers in the paper and textile industry. There seems to be no increased risk of mesothelioma, lung cancer or lung fibrosis in workers exposed to natural organic fibers in contrast to workers exposed to inorganic crystalline fibers as asbestos. However, workers with a heavy exposure to paper dust or textile dust seem to have an increased risk of obstructive lung disease and bronchitis. These effects have not been causally linked to the fibrous shape of the particles but rather to the dust, chemicals absorbed on the dust or microorganisms occurring together with the dust. There is some indication that work in the textile industry may increase the risk of sinonasal cancer, but the etiological agents are unknown.

CONCLUSION: Natural organic fibers are not causally linked with the well-known effects of some inorganic fibers, i.e. mesothelioma, lung cancer, lung fibrosis or some pleural diseases. The health effects of natural organic fibers, e.g. irritative effects, seem not to be linked to their fibrous shape.}, } @article {pmid10968562, year = {2000}, author = {Muhle, H and Pott, F}, title = {Asbestos as reference material for fibre-induced cancer.}, journal = {International archives of occupational and environmental health}, volume = {73 Suppl}, number = {}, pages = {S53-9}, doi = {10.1007/pl00014627}, pmid = {10968562}, issn = {0340-0131}, mesh = {Adult ; Aged ; Animals ; Asbestos/*adverse effects/toxicity ; Biotransformation ; Humans ; Mesothelioma/epidemiology/*etiology ; Middle Aged ; Mineral Fibers/*adverse effects/toxicity ; Occupational Exposure/*adverse effects ; Rats ; Reference Values ; Respiratory Tract Neoplasms/epidemiology/*etiology ; Risk Assessment/methods ; }, abstract = {The objective of this paper is to review published data on the carcinogenicity of asbestos fibres with regard to the elucidation of a potential risk originating from exposure to man-made vitreous fibres (MMVF). Steps in the comparison of the two fibre classes are characterization of the fibres, pulmonary deposition, biodurability and biopersistence and a review of the cancer risk from asbestos fibres after inhalation in rats and humans. Various dust samples of chrysotile, crocidolite, and amosite were used as reference materials in studies with experimental animals. These fibres are normally thinner and shorter than MMVF. These differences in dimensions cause differences in the deposition in the airways. In addition, significant dissimilarities exist in the deposition pattern between rats and humans. Data from biopersistence studies show that focusing only on fibres longer than 20 microm and using weighted half-time for a characterization of risk may be misleading. Inhalation experiments with rats need fibre exposure concentrations over 100 times higher to match the lung cancer risk of asbestos workers, and about 1,000 times higher to reach the same mesothelioma risk. Also, the striking difference between the low lung burden of amphibole fibres of asbestos workers with mesothelioma and the more than 1,000 times higher lung burden of rats with a low mesothelioma risk demonstrates the low sensitivity of the inhalation test model for the carcinogenic potency even of crocidolite fibres. It can be concluded that the rat inhalation model is also not sensitive enough to predict the cancer risk of other fibre types for humans.}, } @article {pmid10967842, year = {2000}, author = {Szeszenia-Dabrowska, N and Wilczyńska, U and Szymczak, W}, title = {Mortality of workers at two asbestos-cement plants in Poland.}, journal = {International journal of occupational medicine and environmental health}, volume = {13}, number = {2}, pages = {121-130}, pmid = {10967842}, issn = {1232-1087}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Cohort Studies ; Female ; Humans ; Male ; Mesothelioma/etiology/mortality ; Middle Aged ; Neoplasms/etiology/*mortality ; Occupational Diseases/etiology/*mortality ; Pleural Neoplasms/etiology/mortality ; Poland/epidemiology ; Sex Distribution ; }, abstract = {To assess mortality rate among workers occupationally exposed to asbestos, cohort studies were carried out in two asbestos cement plants operating since the 1960s. Asbestos cement sheets for roofing and siding have been manufactured there, using mostly chrisotile, and since 1985 also crocidolite for pressure pipes. In all, the cohort comprised 3,220 workers, including 2,616 male workers. Subject to consideration were the workers employed for at least three months in the period between the onset of the production and 1980. The vital status of the subjects was traced up to 31 December 1991. The availability of the cohort was 96.8%. Workers' mortality was analysed using standardized mortality ratio (SMR). The reference group was the general population of Poland. In the male cohort, 385 cases of death were recorded. Statistically significant excess of mortality from large intestine cancer (7 cases, SMR = 264) and pleural mesothelioma (5 cases, SMR = 2846) was found. In male workers who died from pleural mesothelioma the work history ranged from 12 to 26 years. An excess mortality from pleural mesothelioma was also noted among the female workers (2 cases, SMR = 11,275). No malignant neoplasms of other locations produced significant excess mortality either in the male or female workers.}, } @article {pmid10965606, year = {2000}, author = {Gerosa, A and Ietri, E and Belli, S and Grignoli, M and Comba, P}, title = {[High risk of pleural mesothelioma among the state railroad carriage repair workers].}, journal = {Epidemiologia e prevenzione}, volume = {24}, number = {3}, pages = {117-119}, pmid = {10965606}, issn = {1120-9763}, mesh = {Humans ; Italy/epidemiology ; Mesothelioma/*epidemiology ; Occupational Diseases/*epidemiology ; Pleural Neoplasms/*epidemiology ; Prevalence ; *Railroads ; Risk Factors ; }, abstract = {Exposure to asbestos in a facility for the repair of railroad carriages in Bologna was initially studied in 1980, when the Local Health Unit started a program of primary prevention on request of the Unions. At that time workers employed in jobs with high exposure to asbestos were identified. The mortality experience of these 173 subjects was investigated from 01.01.1979 through 31.12.1997, and compared to that of the population of Emilia Romagna. SMR for all causes was 69, with upper limit of the confidence interval lower than 100; this was largely due to a significant decrease of cardiovascular mortality. Among neoplasms, there was a significant excess of pleural mesothelioma (6 observed, 0.09 expected); one more subject died for peritoneal mesothelioma and one for malignant mesothelioma of unspecified site. About half of the subjects deceased for neoplastic disease (8/17) were affected by mesothelioma.}, } @article {pmid10954758, year = {2000}, author = {Klein, G}, title = {Simian virus 40 and the human mesothelium.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {97}, number = {18}, pages = {9830-9831}, pmid = {10954758}, issn = {0027-8424}, mesh = {Asbestos/*adverse effects/toxicity ; *Cell Transformation, Neoplastic ; Epithelial Cells/drug effects/*pathology/*virology ; Humans ; Mesothelioma/*etiology/virology ; Simian virus 40/*pathogenicity ; }, } @article {pmid10954737, year = {2000}, author = {Bocchetta, M and Di Resta, I and Powers, A and Fresco, R and Tosolini, A and Testa, JR and Pass, HI and Rizzo, P and Carbone, M}, title = {Human mesothelial cells are unusually susceptible to simian virus 40-mediated transformation and asbestos cocarcinogenicity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {97}, number = {18}, pages = {10214-10219}, pmid = {10954737}, issn = {0027-8424}, support = {CA-77220-1/CA/NCI NIH HHS/United States ; }, mesh = {Asbestos/*toxicity ; Carcinogens/*toxicity ; *Cell Transformation, Neoplastic ; Cells, Cultured ; Epithelial Cells/drug effects/*pathology/virology ; Fibroblasts/cytology/drug effects/virology ; Humans ; Mesothelioma/etiology/*pathology/virology ; *Simian virus 40 ; Tumor Suppressor Protein p53/genetics/metabolism ; }, abstract = {Mesothelioma, a malignancy associated with asbestos, has been recently linked to simian virus 40 (SV40). We found that infection of human mesothelial cells by SV40 is very different from the semipermissive infection thought to be characteristic of human cells. Mesothelial cells are uniformly infected but not lysed by SV40, a mechanism related to p53, and undergo cell transformation at an extremely high rate. Exposure of mesothelial cells to asbestos complemented SV40 mutants in transformation. Our data provide a mechanistic explanation for the ability of SV40 to transform mesothelial cells preferentially and indicate that asbestos and SV40 may be cocarcinogens.}, } @article {pmid10954257, year = {2000}, author = {La Vecchia, C and Decarli, A and Peto, J and Levi, F and Tomei, F and Negri, E}, title = {An age, period and cohort analysis of pleural cancer mortality in Europe.}, journal = {European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP)}, volume = {9}, number = {3}, pages = {179-184}, pmid = {10954257}, issn = {0959-8278}, mesh = {Adult ; Age Distribution ; Aged ; *Cause of Death ; Cohort Studies ; Europe/epidemiology ; Humans ; Incidence ; Male ; Middle Aged ; Pleural Neoplasms/diagnosis/*mortality ; Poisson Distribution ; Registries ; Risk Factors ; Survival Analysis ; }, abstract = {Death certification data from pleural cancer in eight European countries providing data to the World Health Organization database over the period 1970-1994 were analysed using a log-linear Poisson model to disentangle the effects of age, birth cohort and period of death. The age effect reached values between 10 and 15/100,000 males at age 80-84 in most countries, except Hungary (6.7), Switzerland (18.0), France (20.6) and the Netherlands (36.5). Cohort effects were steadily and appreciably upwards in all countries up to the generations born in 1940 or 1945, and levelled off for the 1950 cohort, except in Hungary, where persistent rises were observed. Thus, most rises in pleural cancer mortality in Europe were on a cohort of birth basis. Since most pleural cases were asbestos-related mesotheliomas, and since asbestos has an early-stage effect on subsequent mesothelioma risk, exposure early in life is important for determining the subsequent mesothelioma risk of each generation. Consequently, the data indicate that the peak mortality from pleural cancer in most western European countries will be reached in the first decades of the 21st century, i.e. around 2010-2020, when the generations born between 1940 and 1950 will reach the peak age for mesothelioma incidence and mortality. This contrasts with US data, where the peak of pleural cancer incidence has been reached at the end of the 20th century, and reflects a delay in adopting adequate prevention measures since the 1940-1945 generations entered the workforce in the 1960s, when cancer risk from asbestos exposure was already recognized.}, } @article {pmid10949869, year = {2000}, author = {Olut, AI and Ertugrul, DT and Kocagoz, T and Er, M and Emri, S}, title = {HHV-8 is not a cofactor in the pathogenesis of environmentally induced malignant pleural mesothelioma.}, journal = {Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace}, volume = {55}, number = {2}, pages = {110-113}, pmid = {10949869}, issn = {1122-0643}, mesh = {Adult ; Aged ; DNA, Viral/*analysis ; Electrophoresis, Polyacrylamide Gel ; Female ; Herpesvirus 8, Human/*isolation & purification ; Humans ; Male ; Mesothelioma/*virology ; Middle Aged ; Pleural Neoplasms/*virology ; Turkey ; }, abstract = {After the recognition of human herpes virus 8 (HHV-8) in Kaposi's sarcoma lesions, this new virus has been shown to be associated with various types of malignancy. One of them, body cavity-based lymphoma, is a high grade B-cell lymphoma arising from the body cavities. Similarly, mesothelioma is a tumour that originates from the serosal linings of the pleural, pericardial and peritoneal cavities. One of the striking characteristics of mesothelioma cells is the secretion of interleukin-6 (IL-6). Also, it is known that HHV-8 upregulates the levels of IL-6, and this virally originated IL-6 is a well-established growth factor for HHV-8-associated lesions. Therefore, it was hypothesized that HHV-8 may have a role in the pathogenesis of malignant mesothelioma. Twenty-nine pleural biopsy specimens from environmentally induced malignant mesothelioma patients were investigated for the presence of HHV-8 deoxyribonucleic acid (DNA) using the polymerase chain reaction (PCR). Control pleural samples were collected from 15 biopsy specimens from patients with tuberculosis. From all samples, a segment of the beta-globulin gene was amplified in order to make sure that the DNA was extracted properly and did not contain any inhibitors. The specificity of the PCR amplification was confirmed by means of restriction enzyme analysis using Providencia stuartii I. PCR did not reveal HHV-8 DNA in any of the mesothelioma patients or in the control group. It was possible to amplify a segment of the human beta-globulin gene from all the samples of the patient and control groups. HHV-8 DNA was amplified in the control sample, which was a tissue biopsy specimen from a Kaposi's sarcoma lesion, and it was confirmed that the amplified DNA belonged to HHV-8 by restriction enzyme analysis. Malignant mesothelioma continues to be a public health problem in rural parts of Anatolia, Turkey. The major causal factor of the disease is exposure to asbestos and fibrous zeolite (erionite). It seems that there must be some aetiological factors other than exposure to these minerals as not all patients exposed to asbestos develop the disease and the disease is not always associated with any known exposure. From the present study, it was concluded that human herpes virus 8 does not seem to be associated with environmentally induced malignant mesothelioma in Turkey. Other possible causal factors of malignant mesothelioma should be sought.}, } @article {pmid10940805, year = {2000}, author = {Gloeckner-Hofmann, K and Zhu, XZ and Bartels, H and Feller, AC and Merz, H}, title = {Deciduoid pleural mesothelioma affecting a young female without prior asbestos exposure.}, journal = {Respiration; international review of thoracic diseases}, volume = {67}, number = {4}, pages = {456-458}, doi = {10.1159/000029549}, pmid = {10940805}, issn = {0025-7931}, mesh = {Adenocarcinoma/pathology/secondary ; Adult ; Asbestos ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; Mesothelioma/metabolism/*pathology/surgery ; Pleural Neoplasms/metabolism/*pathology/surgery ; }, abstract = {Pleural mesothelioma is commonly associated to asbestos exposure. A 40-year-old woman is described who presented with shortness of breath. She had a smoking history but no history of asbestos exposure. Chest radiography and computed tomography showed a large tumour on the right lower lung. An open pleural biopsy was performed. A metastatic adenocarcinoma of the pleura was primarily diagnosed. The tumour progressed and after surgical excision an accurate histological and immunohistochemical examination was performed. It revealed a pleural mesothelioma with a deciduoid differentiation that has not been described before.}, } @article {pmid10939609, year = {2000}, author = {Poggi, A and Longo, F and Mansueto, G and Scirocchi, R and De Petris, L and Gemma, D and Borgomastro, A and Marchei, P}, title = {A case of mesothelioma of the tunica vaginalis testis, with involvement of the pleura and peritoneum.}, journal = {Tumori}, volume = {86}, number = {3}, pages = {256-257}, doi = {10.1177/030089160008600315}, pmid = {10939609}, issn = {0300-8916}, mesh = {Asbestos/adverse effects ; Fatal Outcome ; Humans ; Male ; Mesothelioma/chemically induced/*secondary/therapy ; Middle Aged ; Occupational Exposure/adverse effects ; Peritoneal Neoplasms/chemically induced/*secondary/therapy ; Pleural Neoplasms/chemically induced/*secondary/therapy ; Testicular Neoplasms/chemically induced/*pathology/therapy ; }, } @article {pmid10935940, year = {2000}, author = {Lewis, RJ and Schnatter, AR and Katz, AM and Thompson, FS and Murray, N and Jorgensen, G and Thériault, G}, title = {Updated mortality among diverse operating segments of a petroleum company.}, journal = {Occupational and environmental medicine}, volume = {57}, number = {9}, pages = {595-604}, pmid = {10935940}, issn = {1351-0711}, mesh = {Canada/epidemiology ; Cause of Death ; Cohort Studies ; Extraction and Processing Industry/*statistics & numerical data ; Female ; Follow-Up Studies ; Humans ; Male ; Mesothelioma/mortality ; Occupational Diseases/*mortality ; Occupational Exposure/*adverse effects ; Occupations ; *Petroleum ; }, abstract = {OBJECTIVES: To update mortality for 34 560 employees from diverse operating segments of a Canadian petroleum company; and to investigate potential relations with occupational factors.

METHODS: Employees from 1964-83 were linked to the Canadian mortality data base to provide 11 years additional follow up. There were 6760 deaths and 750 683 person-years of follow up compared with 3909 and 428 190, respectively, in the earlier study. Analyses used standardised mortality ratios (SMRs) to compare worker cause specific mortality with the Canadian general population. Duration of employment and latency analyses were performed for causes previously found to be increased in this and other petroleum cohorts, as well as any findings of interest.

RESULTS: For the period 1964-94, employees experienced significantly low overall mortality (SMR=0.86 men, SMR=0.80 women). Kidney cancer, which has been increased in some studies of petroleum workers, was not increased. Acute non-lymphocytic leukaemia in exposed operating segments was consistent with the expected or only slightly, non-significantly increased. The most notable finding was increased deaths from mesothelioma among refinery and petrochemical workers (SMR 8.68; 95% confidence interval (95% CI) 5.51 to 13.03), most of whom were long term employees in jobs with presumed exposure to asbestos (mechanical and pipefitters). Deaths from multiple myeloma among marketing and distribution workers, which were previously increased, remained increased (SMR 2.08; 95% CI 0.95 to 3.95) in the update period 1984-94; however, there was no clear pattern by duration of employment or latency. Aortic aneurysms, which also were previously significantly increased among marketing and distribution workers approached the expected in the update period (SMR 1.18; 95% CI 0. 65-1.98). Analyses by duration of employment showed suggestive trends for aortic aneurysms, but earlier studies of this cohort have not found a relation between aortic aneurysms and exposure to hydrocarbons.

CONCLUSION: The additional 2851 deaths and 322 493 person-years of follow up strengthened the assessment of mortality patterns relative to occupational factors. With the exception of mesothelioma, no clear work related increases in disease were identified.}, } @article {pmid10931785, year = {2000}, author = {Osinubi, OY and Gochfeld, M and Kipen, HM}, title = {Health effects of asbestos and nonasbestos fibers.}, journal = {Environmental health perspectives}, volume = {108 Suppl 4}, number = {Suppl 4}, pages = {665-674}, pmid = {10931785}, issn = {0091-6765}, mesh = {Air Pollutants, Occupational/*adverse effects ; Asbestosis/*etiology ; Carcinogens, Environmental/*adverse effects ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Mineral Fibers/*adverse effects ; }, abstract = {Exposures to asbestos and synthetic fibers remain areas of great concern in the field of occupational lung disease. Despite extensive study, the health effects associated with fibers remains an area of substantial controversy. In particular, effects of fibers at relatively low doses, particularly for mesothelioma, remain a matter of evolving opinion, especially when integrated with the divergence of opinion on relative pathogenicity of different fiber types. Mechanistic studies continue to provide a window into pathogenesis and some hope for understanding dose-response relationships at the lower levels seen in contemporary Western workplaces and the general environment. Changes in clinical assessment based on use of new chest imaging techniques beyond the traditional plain film are also an area of evolution and begin to challenge B-reading as the definitive tool for noninvasive assessment of disease. Public health concerns have to a great extent been transported to the developing world where there is a strong trend toward increased use of asbestos, although it has been virtually eliminated from commerce in most developed countries. For nonasbestos fibers, the major unsettled issues are their relative potencies as carcinogens for the human lung and mesothelium and the need to sort out the relation between physical and chemical properties of these fibers and their pathogenicity. The recent discovery of "flock worker's lung" due to synthetic fibers once again alerts us to emerging diseases associated with new technologies.}, } @article {pmid10931239, year = {2000}, author = {Attanoos, RL and Gibbs, AR}, title = {Primary malignant gonadal mesotheliomas and asbestos.}, journal = {Histopathology}, volume = {37}, number = {2}, pages = {150-159}, doi = {10.1046/j.1365-2559.2000.00942.x}, pmid = {10931239}, issn = {0309-0167}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Calbindin 2 ; Carcinogens/*adverse effects ; Fatal Outcome ; Female ; Humans ; Hyaluronan Receptors/analysis ; Immunohistochemistry ; Keratins/analysis ; Male ; Mesothelioma/chemically induced/metabolism/*pathology ; Middle Aged ; Ovarian Neoplasms/chemically induced/metabolism/*pathology ; S100 Calcium Binding Protein G/analysis ; Testicular Neoplasms/chemically induced/metabolism/*pathology ; Thrombomodulin/analysis ; }, abstract = {AIMS: The clinicopathological, immunohistochemical and aetiological aspects, with respect to asbestos, of seven primary gonadal mesotheliomas (three intratesticular, four ovarian) are described and compared. These tumours are extremely rare, poorly described and the knowledge of their natural history is very limited.

METHODS AND RESULTS: The cases were collated from the UK Health and Safety Executive Mesothelioma Register over a 24-year period (1968-91). Primary mesotheliomas of the tunica vaginalis and ovary comprised 0. 09% (10 cases) and 0.03% (three cases) of mesothelioma deaths, respectively. No primary intratesticular (non-tunica vaginalis) malignant mesotheliomas have been described. In this study, we present seven (three intratesticular, four ovarian) primary malignant gonadal mesotheliomas. In both genders the tumours show a similar age distribution (with median onset in the sixth decade), a similar association with asbestos (in approximately 50% cases), a diverse histological spectrum (with predominantly tubulopapillary epithelial subtype tumours) and an immunophenotype that is comparable with malignant pleural and peritoneal mesothelioma. The clinical course appears variable (mean, 26 months; range, 9-50 months). All tumours in the study presented as localized masses and their prognosis appeared more favourable than that of diffuse pleural and peritoneal cases.

CONCLUSIONS: An awareness of the existence of these rare forms of malignant mesothelioma is important to prevent misdiagnosis. Immunohistochemistry has an important role in confirmation of the diagnosis. The accurate diagnosis of primary gonadal mesothelioma has potentially important medicolegal compensation considerations as a significant proportion of these cases are associated with asbestos.}, } @article {pmid10919635, year = {2000}, author = {Marrogi, A and Pass, HI and Khan, M and Metheny-Barlow, LJ and Harris, CC and Gerwin, BI}, title = {Human mesothelioma samples overexpress both cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (NOS2): in vitro antiproliferative effects of a COX-2 inhibitor.}, journal = {Cancer research}, volume = {60}, number = {14}, pages = {3696-3700}, pmid = {10919635}, issn = {0008-5472}, mesh = {Adult ; Aged ; Amidines/pharmacology ; Anti-Inflammatory Agents, Non-Steroidal/*pharmacology ; Asbestos/adverse effects ; Benzylamines/pharmacology ; Cell Division/drug effects ; Cyclooxygenase 2 ; Cyclooxygenase 2 Inhibitors ; Cyclooxygenase Inhibitors/pharmacology ; Dose-Response Relationship, Drug ; Enzyme Inhibitors/pharmacology ; Female ; Humans ; Immunohistochemistry ; Isoenzymes/*antagonists & inhibitors/*biosynthesis/*pharmacology ; Lung/drug effects/metabolism ; Lung Neoplasms/drug therapy/*enzymology/etiology/mortality ; Male ; Membrane Proteins ; Mesothelioma/drug therapy/*enzymology/etiology/mortality ; Middle Aged ; Nitric Oxide Synthase/*biosynthesis ; Nitric Oxide Synthase Type II ; Nitrobenzenes/pharmacology ; Prostaglandin-Endoperoxide Synthases/*biosynthesis/*pharmacology ; Sulfonamides/pharmacology ; Time Factors ; Tumor Cells, Cultured ; }, abstract = {Accumulating data demonstrate overexpression of both inducible NO synthase (NOS2) and cyclooxygenase-2 (COX2) in many epithelial neoplasias. In addition, cyclooxygenase inhibitors have been shown to have antineoplastic and prophylactic efficacy against human colon cancer and in mouse models of this disease. Mesothelioma arises in a context of asbestos exposure and chronic inflammation, which would be expected to enhance the expression of these inducible enzymes. This study demonstrates that both inducible enzymes were expressed in 30 human mesothelioma tissues but were not detectable in nonreactive mesothelial tissues from the same individuals. In contrast, areas of reactive mesothelial cells stained positively for these enzymes. In vitro exposure of human mesothelioma cell lines to the COX2 inhibitor, NS398, revealed dose- and time-dependent antiproliferative activity, whereas the NOS2 inhibitor, 1400W, had no detectable inhibitory effect. Surprisingly, nonmalignant human mesothelial isolates expressed both NOS2 and COX2 in vitro at the same level as mesothelioma cell lines but were less sensitive to NS398 inhibition. This finding indicates that these nonmalignant isolates may retain properties of reactive mesothelial cells and suggests that targets in addition to COX2 may be involved in the antiproliferative response of mesothelioma cell lines. These results have clinical significance because of the selective activity of the drug coupled with the therapeutic resistance and poor prognosis of mesothelioma. The findings presented here suggest that further preclinical studies of these inhibitors in animal models of mesothelioma would be of great interest.}, } @article {pmid10921040, year = {1998}, author = {Dou, J and Yu, S and Bian, C}, title = {[Clinical analysis of 19 patients with pleural mesothelioma].}, journal = {Zhonghua zhong liu za zhi [Chinese journal of oncology]}, volume = {20}, number = {5}, pages = {387-388}, pmid = {10921040}, issn = {0253-3766}, mesh = {Adult ; Aged ; Female ; Humans ; Lung Neoplasms/secondary ; Male ; *Mesothelioma/diagnostic imaging/secondary ; Middle Aged ; *Pleural Neoplasms/diagnostic imaging/pathology ; Radiography ; Ultrasonography ; }, abstract = {OBJECTIVE: To summarize the experience in the diagnosis of pleural mesothelioma.

METHODS: Analysing the clinical data of 19 patients with pleural mesothelioma, including age, history of exposure to asbestos, clinical manifestations, imaging and laboratory examinations and metastases.

RESULTS: None of the 19 patients had history of exposure to asbestos. Eight cases(42.1%) had no obvious thoracodynia, 9 cases(47.4%) had pleural effusion limited to the right chest, and in 2 cases(10.5%) the brachialis plexus was involved, and in 1 case (5.3%) malignant mesothelial cells were detected in the pleural effusion. Pleural thickening or nodules were found in 13 cases on CT and in 9 cases by B ultrasonographic examination.

CONCLUSION: Exposure to asbestos is not the only cause of pleural mesothelioma. Chest pain is not always associated with pleural mesothelioma. CT and B ultrasonography are of good help in the diagnosis of pleural mesothelioma.}, } @article {pmid10912648, year = {2000}, author = {Orenstein, MR and Schenker, MB}, title = {Environmental asbestos exposure and mesothelioma.}, journal = {Current opinion in pulmonary medicine}, volume = {6}, number = {4}, pages = {371-377}, doi = {10.1097/00063198-200007000-00020}, pmid = {10912648}, issn = {1070-5287}, support = {ES05707/ES/NIEHS NIH HHS/United States ; R03CA81615-01/CA/NCI NIH HHS/United States ; U07/CCU906162-08//PHS HHS/United States ; }, mesh = {Asbestos/*adverse effects ; Canada/epidemiology ; *Environmental Exposure ; Europe/epidemiology ; Greece/epidemiology ; Humans ; Lung Neoplasms/epidemiology/*etiology ; Mesothelioma/epidemiology/*etiology ; Occupational Exposure ; Turkey/epidemiology ; United States/epidemiology ; }, abstract = {Epidemiologic studies of mesothelioma have focused primarily on occupational exposures to asbestos. Nonoccupational exposure to asbestos can be grouped into three main categories: paraoccupational (familial), neighborhood, and true environmental exposures. Elevated mesothelioma rates not attributable to occupational exposures have been observed in asbestos mining and manufacturing areas. Asbestos is one of the most dangerous environmental carcinogens because of the small dose known to cause mesothelioma and the rapid lethality of the disease once it develops. Further research is needed to characterize the contribution and risk profile for environmental asbestos and mesothelioma, and for the development of public health policy.}, } @article {pmid10912551, year = {2000}, author = {Howel, D and Arblaster, L}, title = {Identifying industrial sites with potential for residential exposure to asbestos.}, journal = {Journal of public health medicine}, volume = {22}, number = {2}, pages = {146-148}, doi = {10.1093/pubmed/22.2.146}, pmid = {10912551}, issn = {0957-4832}, mesh = {Asbestos/adverse effects/*analysis ; Bias ; Carcinogens/adverse effects/*analysis ; Case-Control Studies ; Directories as Topic ; England/epidemiology ; Environmental Exposure/adverse effects/*analysis/*statistics & numerical data ; Environmental Monitoring/*methods ; Epidemiological Monitoring ; Humans ; Industry/*statistics & numerical data/trends ; Mesothelioma/chemically induced/epidemiology ; Residence Characteristics/*statistics & numerical data ; Risk Assessment/*methods ; Telephone/statistics & numerical data/trends ; Time Factors ; }, abstract = {BACKGROUND: Non-occupational exposure to asbestos has been of increasing interest, but residential exposure to asbestos often focuses on a few high-profile asbestos users. This study aimed to identify industrial sites producing asbestos goods in a given area and time period.

METHODS: A search of trade directories was carried out for industrial sites in West Yorkshire, England, where asbestos may have been used this century.

RESULTS: A large number of factories with potential for residential exposure were found. A total of 269 factories in West Yorkshire used asbestos between 1900 and 1979, many for short periods only.

CONCLUSIONS: Identification of potential sources of residential exposure to asbestos would have greatly underestimated their number if either only high-profile users or existing official listings had been used. Any consideration of asbestos use should aim to identify all users, not just the high-profile manufacturers.}, } @article {pmid10897856, year = {1999}, author = {Frimat, P and Paris, C and Letourneux, M and Catilina, P and Sobaszek, A}, title = {[Screening of diseases associated with asbestos. On-going activities, synthesis].}, journal = {Revue des maladies respiratoires}, volume = {16}, number = {6 Pt 2}, pages = {1350-1355}, pmid = {10897856}, issn = {0761-8425}, mesh = {Asbestosis/*complications/*diagnosis ; Bronchial Neoplasms/etiology ; Humans ; Mass Screening ; Mesothelioma/etiology ; }, abstract = {Medical screening requires always assessment. On the basis of ongoing studies on occupational health asbestos programs, we suggest some recommendations for asbestos screening after occupational exposure. The proposal for asbestos workers post-exposure surveillance should take into account the medical but also the social aspects of the problem. Post-exposure screening of asbestos workers includes an evaluation of occupational exposure, compulsory basis medical check-up, the characteristics of the radiological investigations and schedule of the medical surveillance. In conclusion, we suggest some general recommendations for asbestos screening after occupational exposure, particularly the necessity to obtain a concerted approach of asbestos screening with regional and national networks, the concern of their assessment and the implementation of specific research studies.}, } @article {pmid10897854, year = {1999}, author = {Bergeret, A and Terrasson De Fougères, G}, title = {[Social impact of screening and of medical surveillance on people exposed to asbestos].}, journal = {Revue des maladies respiratoires}, volume = {16}, number = {6 Pt 2}, pages = {1327-1331}, pmid = {10897854}, issn = {0761-8425}, mesh = {*Asbestosis/diagnosis/economics/psychology ; Cost of Illness ; France ; Humans ; Mass Screening ; Occupational Exposure ; Population Surveillance ; Public Health ; Workers' Compensation ; }, abstract = {A medical screening program has collective and individual impact. The collective benefit of medical screening for people exposed to asbestos would be financial (better compensation of occupational diseases related to asbestos). The cost of compensation would be attributed to the special assurance fund for occupational diseases. A medical screening of asbestos diseases would set an example for other Public health problems. It would be important for admission of social damage for the French nation. For individuals, social benefits would be better (compensation during work stop and annuities). But screening can have a negative psychological impact for asymptomatic persons. Persons exposed to asbestos and patients with asbestos diseases are able to quit their job for anticipated retirement. Is it a benefit for patients with mesothelioma or lung cancer? It is a very important benefit for asbestosis. The risk is to change the objective of medical screening into a social screening. The financial and medical benefits of screening for hyaline plaques is very poor. Awarding social damage is important for individuals.}, } @article {pmid10897849, year = {1999}, author = {Goldberg, M}, title = {[Asbestos and risk of cancer: exposure-effect relationships for occupationally exposed populations].}, journal = {Revue des maladies respiratoires}, volume = {16}, number = {6 Pt 2}, pages = {1278-1285}, pmid = {10897849}, issn = {0761-8425}, mesh = {Adult ; Aged ; Asbestosis/*complications ; Female ; Humans ; Lung Neoplasms/epidemiology/*etiology ; Male ; Mesothelioma/epidemiology/etiology ; Middle Aged ; *Occupational Exposure ; Risk Factors ; }, abstract = {For high levels of exposure (> 1 f/ml), the risk of lung cancer increases linearly with the cumulative exposure, and is the same for all types of asbestos; the risk of mesothelioma increases linearly with the level of exposure, is time dependent and higher for amphiboles. The effects of asbestos and smoking for lung cancer are independent, and the probability that a cancer is due to asbestos is the same among smokers and non-smokers. There is no scientific method for quantifying directly the risks associated to low levels of exposure (< 1 f/ml). The only possible approach is to extrapolate from the risks observed at high levels to low levels. Proportionality without threshold between dose and risk is not certain, but is the most plausible model. Using this model, one can expect about 30 additional cases of cancer for 10,000 men exposed at the level of 0.1 f/ml from 20 to 65 years, and about 16 additional cases for 10,000 women. These are high figures compared to other health hazards.}, } @article {pmid10897848, year = {1999}, author = {Letourneux, M}, title = {[Risk assessment of benign asbestosis (dose-effect relationship, time-effect relationship, co-factors)].}, journal = {Revue des maladies respiratoires}, volume = {16}, number = {6 Pt 2}, pages = {1270-1277}, pmid = {10897848}, issn = {0761-8425}, mesh = {Asbestosis/*epidemiology/etiology/pathology ; Bronchial Neoplasms/epidemiology/etiology ; Dose-Response Relationship, Drug ; Environmental Exposure ; Humans ; Lung Neoplasms/epidemiology/etiology ; Risk Assessment ; Time Factors ; }, abstract = {Despite the lack of precision of asbestos exposure assessments and the limitations of the main diagnostic epidemiological tool for asbestos-related diseases (i.e. standard X ray films), several issues concerning the risk of development of asbestos-related diseases are well established. For asbestosis, now a rare disease, the existence of a positive dose-response relationship, with a threshold or no-effect level, has been clearly demonstrated. The slope of the relationship curve is steeper for amphiboles than for chysotile, as it is for increased fiber length. Asbestosis is associated with an increased risk of bronchial carcinoma, however it is now known that exposure to asbestos of itself increases the risk of cancer even in the absence of any radiographic signs of pulmonary fibrosis. Pleural plaques occur even when the level of asbestos exposure is low. They are not only dose-dependent but are also latency-related. They have no prognostic significance in asbestos-exposed workers, but are associated with an increased risk for the subsequent development of mesothelioma and bronchial carcinoma when compared to the risk of the general population. Diffuse pleural thickening is associated with higher levels of asbestos exposure than those associated with pleural plaques. It usually follows a benign pleural effusion, which is a less frequent but earlier consequence of asbestos exposure than the other asbestos-related diseases documented above.}, } @article {pmid10897840, year = {1999}, author = {Laurent, F and Tunon de Lara, M}, title = {[Exposure to asbestos. Role of thoracic imagery in screening and follow-up].}, journal = {Revue des maladies respiratoires}, volume = {16}, number = {6 Pt 2}, pages = {1193-1202}, pmid = {10897840}, issn = {0761-8425}, mesh = {Asbestosis/*diagnosis ; Environmental Exposure ; Follow-Up Studies ; Humans ; Mass Screening ; Tomography, X-Ray Computed ; }, abstract = {Chest radiograph and computed tomography are the most appropriate imaging tools for detecting asbestos-related pleural and parenchymal disease due to their availability and performances. The cost and irradiation delivery of conventional chest X-rays are limited. Technical parameters and reading should be standardized. Digital chest radiograph will progressively replace conventional techniques but technical standards and performance data are lacking. Computed tomography, using spiral or conventional mode, explores the whole lung and pleura. High resolution computed tomography samples both lung and pleura but its sensitivity for parenchymal fibrosis detection is greater. Several methods can be employed and should be recommended to reduce radiation dose in spiral and high resolution computed tomography. Computed tomography is more sensitive and specific than chest radiograph in early detection of pleural plaques and parenchymal fibrosis but is not infallible. The error reading rate of chest radiograph for early detection of bronchial carcinoma is high. Computed tomography is more sensitive but lacks specificity and leads to detect a high rate of lesions the relation to asbestos exposure of which are difficult to establish. No scientific data are available to assess the contribution of imaging in early detection of mesothelioma.}, } @article {pmid10896964, year = {2000}, author = {Kielkowski, D and Nelson, G and Rees, D}, title = {Risk of mesothelioma from exposure to crocidolite asbestos: a 1995 update of a South African mortality study.}, journal = {Occupational and environmental medicine}, volume = {57}, number = {8}, pages = {563-567}, pmid = {10896964}, issn = {1351-0711}, mesh = {Adolescent ; Adult ; Aged ; Asbestos, Crocidolite/*adverse effects ; Child ; Child, Preschool ; Cohort Studies ; Environmental Exposure/*adverse effects ; Female ; Follow-Up Studies ; Humans ; Infant ; Male ; Mesothelioma/*mortality ; Middle Aged ; Risk Factors ; South Africa/epidemiology ; }, abstract = {OBJECTIVE: To find the risk of developing mesothelioma in a cohort born in 1916-36 in Prieska, Northern Cape Province, South Africa.

METHODS: A birth cohort mortality study was carried out in a small town in the Northern Cape Province, South Africa, with a history of crocidolite asbestos mining and milling. The cohort comprised all white births registered in the magisterial district of Prieska from 1916 to 1936, inclusive (2390). Causes of death due to mesothelioma and other cancers as recorded on medical certificates of cause of death were investigated. Person-years analysis was used to calculate mortalities due to mesothelioma, other respiratory cancers, and other non-respiratory cancers. Proportional cancer mortalities were also calculated for mesothelioma and other specific neoplasms.

RESULTS: The follow up rate for the cohort was 74.3% in 1995, and 683 traced members (38.6%) had died. Cause of death was unknown for 6.4% of deaths. There were 118 cases of cancer, 28 of them from mesothelioma, giving a cause specific mortality for mesothelioma of 277 (170-384) per 10(6) person-years. The rates for men and women were 366 and 172 per 10(6) person-years, respectively. The mortality for lung cancer (29 deaths) was 287 (135-436) per 10(6) person-years, and that for other non-respiratory cancers (60 deaths) was 593 (442-745). Two cases of laryngeal and four of colon cancer were observed. All cancer mortality, mesothelioma, and lung cancer proportional cancer mortality ratios were increased.

CONCLUSION: The mortality for mesothelioma in men was twice that in women, probably because men were more likely to have had both occupational and environmental exposure to asbestos. Nevertheless, the mortality in women was still high and is probably indicative of the environmental exposure as white women were rarely employed in the asbestos industry in the Prieska area. Due to the long latency from first exposure to diagnosis of the neoplasm, the cause specific mortality in this cohort could be expected to increase rapidly over the next 10 years.}, } @article {pmid10893511, year = {2000}, author = {Alkhuja, S and Miller, A and Mastellone, AJ and Markowitz, S}, title = {Malignant pleural mesothelioma presenting as spontaneous pneumothorax: a case series and review.}, journal = {American journal of industrial medicine}, volume = {38}, number = {2}, pages = {219-223}, doi = {10.1002/1097-0274(200008)38:2<219::aid-ajim8>3.0.co;2-8}, pmid = {10893511}, issn = {0271-3586}, mesh = {Aged ; Aged, 80 and over ; *Asbestos ; Female ; Humans ; Male ; Mesothelioma/*complications/diagnosis ; Middle Aged ; *Occupational Exposure ; Pleural Neoplasms/*complications/diagnosis ; Pneumothorax/diagnostic imaging/*etiology ; Radiography ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is thought to arise from the mesothelial cells that line the pleural cavities. Most patients initially experience the insidious onset of chest pain or shortness of breath, and it rarely presents as spontaneous pneumothorax.

CASE REPORTS: We report four patients who presented in this manner. Three of the patients were exposed to asbestos directly or indirectly at shipyards during World War II; the fourth was exposed as an insulator's wife. Two of our cases were not recognized to have MPM on histologic examination at first thoracotomy and remained asymptomatic for 12 and 22 months, respectively. In none of the patients described herein, was spontaneous pneumothorax the cause of death.

CONCLUSIONS: Since many people were exposed to asbestos during and after World War II, spontaneous pneumothorax in a patient with the possibility of such exposure should raise the suspicion of malignant pleural mesothelioma.}, } @article {pmid10884164, year = {1999}, author = {}, title = {Call for an international ban on asbestos.}, journal = {Scandinavian journal of work, environment & health}, volume = {25}, number = {6}, pages = {633-635}, pmid = {10884164}, issn = {0355-3140}, mesh = {Asbestos/*adverse effects ; Global Health ; Humans ; *International Cooperation ; Lung Neoplasms/chemically induced ; Mesothelioma/chemically induced ; Mining/legislation & jurisprudence ; Occupational Health/*legislation & jurisprudence ; Societies, Medical ; }, } @article {pmid10883677, year = {2000}, author = {Magnani, C and Agudo, A and González, CA and Andrion, A and Calleja, A and Chellini, E and Dalmasso, P and Escolar, A and Hernandez, S and Ivaldi, C and Mirabelli, D and Ramirez, J and Turuguet, D and Usel, M and Terracini, B}, title = {Multicentric study on malignant pleural mesothelioma and non-occupational exposure to asbestos.}, journal = {British journal of cancer}, volume = {83}, number = {1}, pages = {104-111}, pmid = {10883677}, issn = {0007-0920}, mesh = {Adult ; Aged ; Aged, 80 and over ; Air Conditioning/instrumentation ; Asbestos/*adverse effects ; Case-Control Studies ; Catchment Area, Health ; Construction Materials ; Dose-Response Relationship, Drug ; *Environmental Exposure ; Female ; Heating/instrumentation ; Housing ; Humans ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Odds Ratio ; Pleural Neoplasms/epidemiology/*etiology ; Risk ; Single-Blind Method ; Spain/epidemiology ; Switzerland/epidemiology ; Urban Population ; }, abstract = {Insufficient evidence exists on the risk of pleural mesothelioma from non-occupational exposure to asbestos. A population-based case-control study was carried out in six areas from Italy, Spain and Switzerland. Information was collected for 215 new histologically confirmed cases and 448 controls. A panel of industrial hygienists assessed asbestos exposure separately for occupational, domestic and environmental sources. Classification of domestic and environmental exposure was based on a complete residential history, presence and use of asbestos at home, asbestos industrial activities in the surrounding area, and their distance from the dwelling. In 53 cases and 232 controls without evidence of occupational exposure to asbestos, moderate or high probability of domestic exposure was associated with an increased risk adjusted by age and sex: odds ratio (OR) 4.81, 95% confidence interval (CI) 1.8-13.1. This corresponds to three situations: cleaning asbestos-contaminated clothes, handling asbestos material and presence of asbestos material susceptible to damage. The estimated OR for high probability of environmental exposure (living within 2000 m of asbestos mines, asbestos cement plants, asbestos textiles, shipyards, or brakes factories) was 11.5 (95% CI 3.5-38.2). Living between 2000 and 5000 m from asbestos industries or within 500 m of industries using asbestos could also be associated with an increased risk. A dose-response pattern appeared with intensity of both sources of exposure. It is suggested that low-dose exposure to asbestos at home or in the general environment carries a measurable risk of malignant pleural mesothelioma.}, } @article {pmid10882896, year = {2000}, author = {Marczynski, B and Rozynek, P and Kraus, T and Schlösser, S and Raithel, HJ and Baur, X}, title = {Levels of 8-hydroxy-2'-deoxyguanosine in DNA of white blood cells from workers highly exposed to asbestos in Germany.}, journal = {Mutation research}, volume = {468}, number = {2}, pages = {195-202}, doi = {10.1016/s1383-5718(00)00053-x}, pmid = {10882896}, issn = {0027-5107}, mesh = {8-Hydroxy-2'-Deoxyguanosine ; Adolescent ; Adult ; Aged ; Asbestos/*adverse effects ; Asbestos, Serpentine/adverse effects ; Biomarkers ; DNA Adducts/*analysis ; *DNA Damage ; Deoxyguanosine/*analogs & derivatives/analysis ; Female ; Germany/epidemiology ; Humans ; Leukocytes/*chemistry ; Male ; Middle Aged ; *Occupational Exposure ; Oxidative Stress ; Reactive Oxygen Species ; Smoking ; }, abstract = {Asbestos fibers have genotoxic effects and are a potential carcinogenic hazard to occupationally exposed workers. The ability of inhaled asbestos fibers to induce the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the DNA of white blood cells (WBC) of workers highly exposed at the workplace has been studied. The 8-OHdG adduct level of asbestos-exposed workers was significantly increased (p<0.001) compared to that in the control group in all three years of the study. Asbestos-exposed individuals showed a mean value of 2.61+/-0.91 8-OHdG/10(5) dG (median 2.49, n=496) in 1994-1995, 2.96+/-1.10 8-OHdG/10(5) dG (median 2.76, n=437) in 1995-1996 and 2.55+/-0.56 8-OHdG/10(5) dG (median 2.53, n=447) in 1996-1997. For the control subjects, a mean of 1.52+/-0.39 (median 1.51, n=214) was determined. The results indicate that human DNA samples from exposed individuals contain between 1.7 times and twice the level of oxidative damage relative to that found in control samples in all 3 years of the study. The studies presented here show that asbestos exposure can result in oxidative DNA damage. Our data confirm that oxidative DNA damage occurs in the WBC of workers highly exposed to asbestos fibers, thus supporting the hypothesis that asbestos fibers damage cells through an oxidative mechanism. These in vivo findings underline the importance of oxidative damage in asbestos-induced carcinogenesis and highlight the need for exploring the molecular basis of asbestos-induced diseases, and for more effective diagnosis, prevention and therapy of mesothelioma, lung cancer and pulmonary fibrosis. In addition, preventive and therapeutic approaches using antioxidants may be relevant.}, } @article {pmid10877337, year = {2000}, author = {Rogan, WJ and Ragan, NB and Dinse, GE}, title = {X-ray evidence of increased asbestos exposure in the US population from NHANES I and NHANES II, 1973-1978. National Health Examination Survey.}, journal = {Cancer causes & control : CCC}, volume = {11}, number = {5}, pages = {441-449}, doi = {10.1023/a:1008952426060}, pmid = {10877337}, issn = {0957-5243}, mesh = {Adult ; Age Distribution ; Aged ; Asbestos/*adverse effects ; Asbestosis/diagnostic imaging/*epidemiology ; Environmental Exposure ; Female ; Humans ; Lung Neoplasms/diagnostic imaging/*epidemiology ; Male ; Middle Aged ; Nutrition Surveys ; Occupational Exposure ; Pleural Diseases/*diagnostic imaging ; Precancerous Conditions/*diagnostic imaging ; Prevalence ; Radiography ; United States/epidemiology ; }, abstract = {OBJECTIVES: Jobs involving heavy asbestos exposure increase risk for lung cancer and mesothelioma substantially, and low-level exposures may carry some risk. At least one indicator of asbestos exposure, mesothelioma, has been increasing in the US for decades. We investigated the prevalence of another indicator, pleural thickening on x-ray, in a defined sample of the US population.

METHODS: Certified physicians read 1060 x-rays from the second National Health and Nutrition Examination Survey (1976-1980) for pleural changes consistent with pneumoconiosis, which are a reasonably specific indicator of asbestos exposure.

RESULTS: Prevalence estimates, in NHANES II, in the age group 35-74 years, are 6.4% (+/- 0.9%) among males, 1.7% (+/- 0.6%) among females, and 3.9% (+/- 0.6%) overall. These prevalences are approximately twice those estimated from NHANES I data (1971-1975).

CONCLUSIONS: X-ray evidence of asbestos exposure was common in the late 1970s and increasing. The increase may be due to occupational asbestos exposure, but it is so large as to suggest some contribution from environmental, non-occupational asbestos exposure.}, } @article {pmid10874176, year = {2000}, author = {Bonomo, L and Feragalli, B and Sacco, R and Merlino, B and Storto, ML}, title = {Malignant pleural disease.}, journal = {European journal of radiology}, volume = {34}, number = {2}, pages = {98-118}, doi = {10.1016/s0720-048x(00)00168-6}, pmid = {10874176}, issn = {0720-048X}, mesh = {Asbestos/adverse effects ; Carcinoma, Bronchogenic/*complications ; Female ; Humans ; Liposarcoma/diagnosis ; Magnetic Resonance Imaging ; Male ; Mesothelioma/diagnosis/etiology ; Neoplasm Staging ; Neoplasms, Fibrous Tissue/diagnosis ; Pleural Neoplasms/diagnosis/*diagnostic imaging/etiology/*secondary ; Prognosis ; Tomography, X-Ray Computed ; }, abstract = {The vast majority of pleural neoplasms invade the pleura secondarily and can be seen in patients with bronchogenic carcinoma, breast cancer, lymphoma, and ovarian or gastric carcinoma. Primary pleural neoplasms are less common, although they have developed notoriety since the up-surge of malignant mesothelioma and the knowledge of its connection to asbestos exposure. Other malignant primary tumors include localized fibrous tumor and pleural liposarcoma. In most patients with diffuse malignant pleural disease the chest radiograph shows pleural effusion with or without pleural thickening. Computed tomography (CT) usually provides precise localization and extent of the disease and may be of value in assessing chest wall and mediastinal involvement. In specific situations, magnetic resonance (MR) may be useful as a problem-solving tool when CT findings of chest wall or diaphragmatic invasion are equivocal or in patients with contraindication to intravenous administration of ionic contrast material.}, } @article {pmid10863160, year = {2000}, author = {Ni, Z and Liu, Y and Keshava, N and Zhou, G and Whong, W and Ong, T}, title = {Analysis of K-ras and p53 mutations in mesotheliomas from humans and rats exposed to asbestos.}, journal = {Mutation research}, volume = {468}, number = {1}, pages = {87-92}, doi = {10.1016/s1383-5718(00)00043-7}, pmid = {10863160}, issn = {0027-5107}, mesh = {Animals ; Asbestos/*adverse effects ; Base Sequence ; Carcinogens/*adverse effects ; DNA Mutational Analysis ; DNA Restriction Enzymes/metabolism ; DNA, Neoplasm/chemistry/genetics/metabolism ; Female ; Genes, p53/*genetics ; Genes, ras/*genetics ; Humans ; Male ; Mesothelioma/chemically induced/*genetics ; Mutation ; Occupational Exposure/adverse effects ; Polymerase Chain Reaction ; Polymorphism, Single-Stranded Conformational ; Proto-Oncogene Mas ; Rats ; Rats, Wistar ; }, abstract = {Malignant mesothelioma is known to be associated with asbestos exposure. However, the mechanism of mesothelial carcinogenesis in relation to the activation of proto-oncogenes or inactivation of tumor suppressor genes remains unclear. In this study, the PCR-Primer Introduced Restriction Site (PCR-PIRS) assay was employed to examine mutations in the K-ras proto-oncogene in mesothelioma tissues from workers exposed to asbestos and from rats treated with asbestos. Mutations in exons 5-8 of the p53 tumor suppressor gene were determined by direct DNA sequence analysis. Results of the PCR-PIRS analysis revealed no mutations in codons 12, 13 or 61 of the K-ras gene in any of the 17 human or 22 rat mesothelioma tissue samples. These results were confirmed by direct DNA sequence analysis. No mutations were found in exons 5-8 of the p53 gene in any of the mesothelioma tissue samples analyzed. These results and the results reported by others indicate that the K-ras proto-oncogene and p53 tumor suppressor gene may not play a critical role in the induction of mesothelioma by asbestos either in humans or in rats.}, } @article {pmid10854503, year = {2000}, author = {Banaei, A and Auvert, B and Goldberg, M and Gueguen, A and Luce, D and Goldberg, S}, title = {Future trends in mortality of French men from mesothelioma.}, journal = {Occupational and environmental medicine}, volume = {57}, number = {7}, pages = {488-494}, pmid = {10854503}, issn = {1351-0711}, mesh = {Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Forecasting ; France/epidemiology ; Humans ; Incidence ; Male ; Mesothelioma/*mortality ; Middle Aged ; Occupational Exposure/*adverse effects ; Peritoneal Neoplasms/*mortality ; Pleural Neoplasms/*mortality ; Poisson Distribution ; Risk Factors ; }, abstract = {OBJECTIVES: Previous projections of mortality from mesothelioma among French men have used the age-generation method, based on the Poisson regression model. In this study an alternative method to model mortality from mesothelioma was used to predict its future trend: this method was based on the risk function that links this mortality to past exposure to asbestos, combined with population exposure data.

METHOD: Data on past French asbestos imports were used to model the overall past exposure to asbestos in men and assess two extreme scenarios (optimistic and pessimistic) for its future trends. The number of male deaths occurring between the ages of 50 and 79, from 1997-2050, was then calculated with the risk function for mesothelioma.

RESULTS: The results showed that mortality from mesothelioma among French men aged 50-79 will continue to increase, reaching a peak averaging between 1140 (optimistic scenario) and 1300 deaths (pessimistic scenario) annually around the years 2030 and 2040, respectively. No preventive measures applied now will affect this trend before then. These results are similar to those of two other predictions of mortality from mesothelioma among French men: a peak around 2030 of 800-1600 deaths annually among men aged 25-89 years, and a peak around 2020 of 1550 deaths annually among men aged 40-84.

CONCLUSIONS: Our results indicate that between 1997 and 2050, the most optimistic and pessimistic trends of future exposure will lead to the deaths from mesothelioma of between 44 480 and 57 020 men, with a corresponding loss of from 877 200 to 1 171 500 person-years of life.}, } @article {pmid10854118, year = {2000}, author = {Banaei, A and Auvert, B and Goldberg, M}, title = {Computer modeling of population exposure to a carcinogen: the example of asbestos and mesothelioma mortality in France.}, journal = {Computers and biomedical research, an international journal}, volume = {33}, number = {2}, pages = {97-109}, doi = {10.1006/cbmr.1999.1536}, pmid = {10854118}, issn = {0010-4809}, mesh = {Aged ; Asbestos/*adverse effects ; Carcinogens/*adverse effects ; Cohort Studies ; *Computer Simulation ; France/epidemiology ; Humans ; Male ; Mesothelioma/*etiology/*mortality ; Middle Aged ; Models, Biological ; Occupational Diseases/etiology/mortality ; Occupational Exposure ; Risk Factors ; }, abstract = {The multistage theory of carcinogenesis allows models to be constructed that provide the individual probability of a diagnosed tumor at a given age as a function of the person's past exposure to carcinogenic agents (exposure level versus age), the time since exposure, and age. When exposure to a carcinogenic agent and its impact in terms of morbidity and mortality are modeled on the scale of the general population, individual exposures must often be estimated. If appropriate data do not already exist, this difficult task necessitates expensive and difficult investigations. We propose here a method that allows this global exposure to be modeled without needing to know the individual exposures. The method is used and illustrated in the context of modeling the asbestos exposure of the French male population and calculating its mortality rate from mesothelioma (a type of cancer for which asbestos is the only carcinogen and for which a risk function based on the multistage theory of carcinogenesis exists). This method assumes that the exposure functions (how exposure levels vary with age) for all individuals are the same, with the exception of one parameter. That is, it utilizes a hypothesis that we called the hypothesis of the Standard Exposure Window (SEW). We used two methods to calculate the probability of death from mesothelioma in a representative sample of the French male population for whom individual histories of asbestos exposure are known: we applied the risk function to all the individuals, and we applied the SEW hypothesis. The number of deaths obtained by the two methods are very close and fit the observed mortality data satisfactorily.}, } @article {pmid10843283, year = {2000}, author = {Ordóñez, NG}, title = {Epithelial mesothelioma with deciduoid features: report of four cases.}, journal = {The American journal of surgical pathology}, volume = {24}, number = {6}, pages = {816-823}, doi = {10.1097/00000478-200006000-00006}, pmid = {10843283}, issn = {0147-5185}, mesh = {Aged ; Asbestos/adverse effects ; Child ; Decidua/pathology ; Environmental Exposure ; Female ; Humans ; Immunohistochemistry ; Male ; Mesothelioma/diagnosis/*pathology/surgery ; Middle Aged ; Pleura/pathology ; Pleural Neoplasms/diagnosis/*pathology/surgery ; Pneumonectomy ; }, abstract = {Deciduoid mesothelioma is the designation given to an unusual morphologic variant of epithelial mesothelioma that closely simulates exuberant ectopic decidual reaction. Because all four previously reported cases involved the peritoneum and occurred in young women without a history of asbestos exposure, it was suggested that deciduoid mesothelioma was a subtype of epithelial mesothelioma characterized by its unique morphology, that it affects a distinct patient population, and that it is unrelated etiologically to asbestos. The author reports four cases of mesothelioma with deciduoid features, all of which originated in the pleura. Three of the patients were men and one was a woman. Their ages ranged from 46 to 78 years (mean age, 67 yrs). Two of the patients had a history of asbestos exposure. These findings indicate that this morphologic variant of mesothelioma is not limited to a specific patient population nor is it restricted to the peritoneum.}, } @article {pmid10817376, year = {2000}, author = {Kjaergaard, J and Andersson, M}, title = {Incidence rates of malignant mesothelioma in Denmark and predicted future number of cases among men.}, journal = {Scandinavian journal of work, environment & health}, volume = {26}, number = {2}, pages = {112-117}, doi = {10.5271/sjweh.520}, pmid = {10817376}, issn = {0355-3140}, mesh = {Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Cohort Studies ; Confidence Intervals ; Denmark/epidemiology ; Female ; Humans ; Incidence ; Male ; Mediastinal Neoplasms/diagnosis/*epidemiology ; Mesothelioma/diagnosis/*epidemiology ; Middle Aged ; Peritoneal Neoplasms/diagnosis/*epidemiology ; Poisson Distribution ; Predictive Value of Tests ; Registries ; Risk Factors ; Sex Distribution ; Survival Rate ; }, abstract = {OBJECTIVES: This study analyzed the incidence rates of malignant mesothelioma in Denmark in order to predict the future number of cases that will occur among Danish men.

METHODS: The 1912 cases of malignant mesothelioma reported to the Danish Cancer registry in 1943-1993 were analyzed in order to describe current incidence rates. By a Poisson regression model the relative risks of synthetic birth cohorts were estimated and used in the prediction of the future number of cases that will occur among Danish men.

RESULTS: The incidence rate increased to 1.33 per 100000 person-years in 1983-1987 among men and to 0.51 in 1973-1977 among women. From the Poisson regression model, the risk for birth cohorts of men, relative to the 1940-1944 cohort, peaked in the 1940-1944 cohort and decreased to 0.57 in the 1950-1954 cohort. The age-specific incidence rate peaked at 246 per 100000 person-years in the age group 80-84 years. The future annual number of mesothelioma cases is expected to peak around 2015 with 93 cases among men born before 1955.

CONCLUSIONS: The fit of the models was not ideal, but with careful interpretation of the results, it was concluded that a further increase in the number of mesothelioma cases can be expected, and the effect of regulating the environmental exposure to asbestos cannot be expected within the next 10-15 years.}, } @article {pmid10817374, year = {2000}, author = {Langseth, H and Andersen, A}, title = {Cancer incidence among male pulp and paper workers in Norway.}, journal = {Scandinavian journal of work, environment & health}, volume = {26}, number = {2}, pages = {99-105}, doi = {10.5271/sjweh.518}, pmid = {10817374}, issn = {0355-3140}, mesh = {Adult ; Age Distribution ; Air Pollutants, Occupational/adverse effects ; *Chemical Industry ; Cohort Studies ; Confidence Intervals ; Humans ; Incidence ; Lymphoma/*epidemiology/etiology ; Male ; Middle Aged ; Neoplasms/epidemiology ; Norway/epidemiology ; Occupational Diseases/*epidemiology/etiology ; Paper ; Registries ; Respiratory Tract Neoplasms/*epidemiology/etiology ; Risk Factors ; Smoking/epidemiology ; Survival Rate ; }, abstract = {OBJECTIVES: The study investigated cancer incidence among 23,718 male pulp and paper workers employed continuously for at least 1 year between 1920 and 1993 in Norway.

METHODS: The name, date of birth, personal identification number, dates of hire and termination for all employment periods, specific department, and job categories were registered for each worker. Six subcohorts were established (sulfite mill, sulfate mill, paper mill, maintenance department, administrative staff and other departments). Data on the cohort were linked with data in the Norwegian Cancer Register. The follow-up period for cancer incidence, date of death, or emigration was from 1953 through 1993.

RESULTS: An excess incidence of lung cancer was found among both short- and long-term employees [standardized incidence ratio (SIR) 1.5, 95% confidence interval (95% CI) 1.13-2.03 and SIR 1.2, 95% CI 1.09-1.34, respectively], especially for workers with the longest latency (SIR 1.3, 95% CI 1.08-1.44) and for sulfite mill workers (SIR 1.5, 95% CI 1.09-1.99). The risk for pleural mesothelioma was also increased (SIR 2.4, 95% CI 1.45-3.75), especially among maintenance workers. The results also showed an increased risk for malignant melanoma (SIR 1.3, 95% CI 1.04-1.60), an unexpected finding.

CONCLUSIONS: Almost all the increased risk for lung cancer can be explained by a combination of smoking habits and asbestos use. although an effect of other work-related exposures (sulfur and chloride compounds, wood dust) cannot be excluded. Most of the cases of pleural mesothelioma occurred in departments where asbestos was used. There is no clear explanation for the excess of malignant melanoma, and the finding may be a chance occurrence.}, } @article {pmid10810372, year = {2000}, author = {Emri, S and Kocagoz, T and Olut, A and Güngen, Y and Mutti, L and Baris, YI}, title = {Simian virus 40 is not a cofactor in the pathogenesis of environmentally induced malignant pleural mesothelioma in Turkey.}, journal = {Anticancer research}, volume = {20}, number = {2A}, pages = {891-894}, pmid = {10810372}, issn = {0250-7005}, mesh = {Adult ; Aged ; Asbestos ; Bone Neoplasms/etiology/pathology/virology ; Carcinogens ; *Environmental Exposure ; Female ; Humans ; Male ; Mesothelioma/*etiology/pathology/virology ; Middle Aged ; Osteosarcoma/etiology/pathology/virology ; Pleural Neoplasms/*etiology/pathology/virology ; Turkey ; Zeolites ; }, abstract = {Malignant pleural mesothelioma (MPM) continues to be a public health problem in Turkey, where exposure to environmental asbestos and fibrous zeolite (erionite) is the main cause of the disease. However, less than 5% of exposed individuals develop the disease, and numerous cases of MPM are documented each year in which the patient has no known exposure to either of these minerals. Thus, additional unknown factors act independently or as co-carcinogens in the development of MPM. Simian Virus 40 (SV40) may act as a co-carcinogen with asbestos in the pathogenesis of occupationally induced MPM. To determine if SV40 plays a role in the development of MPM in Turkey, we used PCR analysis to investigate if SV40 DNA sequences were present in 29 mesothelioma specimens from patients previously exposed to asbestos or erionite. PCR analysis revealed that all 29 tissue specimens from our patients did not contain SV40 DNA. 15 specimens from patients suffering from tuberculosis pleuresy were also SV40 negative. One mesothelioma and one osteosarcoma from Italy tested positive for SV40. Our results indicate that inorganic fibers, asbestos, and erionite remain the only known causal factors of mesothelioma in Turkey. The absence of SV40 in Turkish specimens and its presence in Italian specimens may be related to the fact that SV40-contaminated vaccines were not administered in Turkey.}, } @article {pmid10810370, year = {2000}, author = {Arrington, AS and Lednicky, JA and Butel, JS}, title = {Molecular characterization of SV40 DNA in multiple samples from a human mesothelioma.}, journal = {Anticancer research}, volume = {20}, number = {2A}, pages = {879-884}, pmid = {10810370}, issn = {0250-7005}, support = {AI07483/AI/NIAID NIH HHS/United States ; AI36211/AI/NIAID NIH HHS/United States ; }, mesh = {Antigens, Polyomavirus Transforming/*genetics ; Base Sequence ; DNA, Viral/*analysis ; Humans ; Lung Neoplasms/pathology/surgery/*virology ; Lymph Nodes/virology ; Male ; Mesothelioma/pathology/surgery/*virology ; Middle Aged ; Molecular Sequence Data ; Pleural Neoplasms/pathology/surgery/*virology ; Polymerase Chain Reaction ; Sequence Alignment ; Sequence Homology, Nucleic Acid ; Simian virus 40/genetics/*isolation & purification ; Soft Tissue Neoplasms/pathology/virology ; }, abstract = {BACKGROUND: Prolonged exposure to asbestos, a potent carcinogen, has been the generally accepted factor responsible for the development of human mesotheliomas. Recent reports documenting the detection of SV40 DNA in human mesotheliomas suggest the possibility that this known tumor virus may be an additional factor involved in the development of some tumors.

METHODS: A detailed analysis was performed by polymerase chain reaction and DNA sequencing of the genetic characteristics of SV40 viral DNA detected in samples taken from multiple sites of a human mesothelioma.

RESULTS: A single virus variant was detected within the tumor that encoded a novel variable region at the C-terminus of the large T-antigen oncoprotein. The viral regulatory region was predominantly archetypal in sequence (lacking duplications of the enhancer), typical of natural isolates.

CONCLUSIONS: These data confirm previous reports from several laboratories showing an association of SV40 DNA with human mesotheliomas and provide the first evidence of a novel virus variant present in separated regions of a mesothelioma.}, } @article {pmid10810369, year = {2000}, author = {Carbone, M and Rizzo, P and Pass, H}, title = {Simian virus 40: the link with human malignant mesothelioma is well established.}, journal = {Anticancer research}, volume = {20}, number = {2A}, pages = {875-877}, pmid = {10810369}, issn = {0250-7005}, support = {CA-74283/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Asbestos/adverse effects ; Cricetinae ; Europe ; Heart Neoplasms/epidemiology/virology ; Humans ; Incidence ; Mesothelioma/epidemiology/etiology/*virology ; Pericardium ; Peritoneal Neoplasms/epidemiology/virology ; Pleural Neoplasms/epidemiology/virology ; Simian virus 40/isolation & purification/*pathogenicity ; United States/epidemiology ; }, abstract = {Mesotheliomas are malignancies of the pleural, pericardial, and peritoneal surfaces with a mean survival of less than 1 year from the time of diagnosis (1). While mesotheliomas were extremely rare in the first half of this century, the incidence of these tumors has increased enormously in the last several decades. Presently, 2-3 thousand people in the US develop and die of mesothelioma each year (1). It is estimated that approximately 80% of mesotheliomas develop in people with a history of occupational asbestos exposure or in individuals with family member(s) professionally exposed to asbestos that brought home fibers on their clothing (1). Although conventional wisdom dictates that asbestos is the most commonly associated "environmental" factor with mesothelioma, asbestos does not transform human mesothelioma cells in tissue culture (2). This suggests that additional carcinogens act in concert with asbestos to cause mesothelioma. Recent evidence indicated that Simian Virus 40 (SV40) preferentially causes mesotheliomas in hamsters, and that SV40 is present in up to 80% of human mesotheliomas in the US and in Europe (reviewed in ref. 3 and 4).}, } @article {pmid10808262, year = {2000}, author = {Fowler, DP}, title = {Exposures to asbestos arising from bandsawing gasket material.}, journal = {Applied occupational and environmental hygiene}, volume = {15}, number = {5}, pages = {404-408}, doi = {10.1080/104732200301359}, pmid = {10808262}, issn = {1047-322X}, mesh = {Asbestos/*analysis ; Humans ; Industry ; Inhalation Exposure ; Materials Testing ; Neoprene/*chemistry ; Occupational Exposure/*analysis ; Particle Size ; United States ; United States Occupational Safety and Health Administration ; }, abstract = {A simulation of bandsawing sheet asbestos gasket material was performed as part of a retrospective exposure evaluation undertaken to assist in determining causation of a case of mesothelioma. The work was performed by bandsawing a chrysotile asbestos (80%)/neoprene gasket sheet with a conventional 16-inch woodworking bandsaw inside a chamber. Measurements of airborne asbestos were made using conventional area and personal sampling methods, with analysis of collected samples by transmission electron microscopy (TEM) and phase contrast microscopy (PCM). These were supplemented by qualitative scanning electron microscopy (SEM) examinations of some of the airborne particles collected on the filters. In contrast with findings from studies examining manual handling (installation and removal) of gaskets, airborne asbestos concentrations from this operation were found to be well above current Occupational Safety and Health Administration (OSHA) permissible exposure limit (PEL) (eight-hour time-weighted average [TWA]) and excursion limit (30-minute) standards. Although some "encapsulation" effect of the neoprene matrix was seen on the particles in the airborne dust, unencapsulated individual fiber bundles were also seen. Suggestions for the implications of the work are given. In summary, the airborne asbestos concentrations arising from this work were quite high, and point to the need for careful observation of common sense precautions when manipulation of asbestos-containing materials (even those believed to have limited emissions potential) may involved machining operations.}, } @article {pmid10786419, year = {2000}, author = {Rodriguez-Panadero, F}, title = {Malignant pleural diseases.}, journal = {Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace}, volume = {55}, number = {1}, pages = {17-19}, pmid = {10786419}, issn = {1122-0643}, mesh = {Humans ; Pleural Effusion, Malignant/*diagnosis/*therapy ; Pleurodesis ; Thoracoscopy ; }, abstract = {The incidence of malignant pleural effusions has been increasing over the last few decades (mainly due to the absolute increase in several types of cancers, especially those of lung and breast origin) and they account for up to 50% of the exudates in many clinical series. Although pleural malignancies are thought to present most frequently with a pleural effusion, several autopsy series, including the current one, found a pleural effusion present in little more than half of the cases of malignant pleural involvement (55% in this series). Thus, many pleural malignancies without effusion might pass unnoticed in clinical practice, especially in metastatic disease. Primary malignancies of the pleura (mesotheliomas) are associated with asbestos exposure in about two-thirds of cases, and they frequently present with chest pain, sometimes associated with a pleural effusion. Benign pleural plaques can coexist with malignant mesothelioma, and this association should be suspected when long-standing plaques change in shape or size over the years, and especially if chest pain develops in a previously asymptomatic patient. Metastatic pleural involvement is much more frequent than mesotheliomas, and its most frequent mechanism is the vascular spreading of tumour cells from distant organs to the lungs, and on to the visceral and parietal pleura. The visceral pleura was involved in up to 87% of the current metastatic cases, whereas the parietal zone in only 47% of the autopsy series. The diagnostic work-up lies in cytology, whose average yield is approximately 50%, and a biopsy technique (either by blind needle biopsy or thoracoscopy) is recommended when the effusion persists, for > 2 weeks, and the first cytology has been negative. Thoracoscopy has the additional advantage of allowing pleurodesis with talc poudrage if clear tumour lesions are found in the pleura. In cases of malignant effusion which are not sensitive to chemotherapy, pleurodesis is the treatment of choice for palliation of symptoms, and talc is the most effective agent. It can be used either in suspension ("slurry") or in dry aerosolized form ("talc poudrage"), but it seems that this last technique achieves the best effects. However, it requires thoracoscopy for a proper application, and this is its main drawback when that technique is not readily available.}, } @article {pmid10783328, year = {2000}, author = {Sandhu, H and Dehnen, W and Roller, M and Abel, J and Unfried, K}, title = {mRNA expression patterns in different stages of asbestos-induced carcinogenesis in rats.}, journal = {Carcinogenesis}, volume = {21}, number = {5}, pages = {1023-1029}, doi = {10.1093/carcin/21.5.1023}, pmid = {10783328}, issn = {0143-3334}, mesh = {Animals ; Asbestos, Crocidolite/*toxicity ; Base Sequence ; Carcinogens/*toxicity ; Cell Transformation, Neoplastic/*genetics ; DNA Primers ; ErbB Receptors/genetics ; Genes, myc ; Mesothelioma/chemically induced/*genetics ; Precancerous Conditions/chemically induced/genetics ; Proto-Oncogene Mas ; Proto-Oncogene Proteins c-fos/genetics ; RNA, Messenger/*genetics ; Rats ; Rats, Wistar ; Reverse Transcriptase Polymerase Chain Reaction ; Up-Regulation ; }, abstract = {Human malignant mesotheliomas are induced almost exclusively by fibrous dusts. The nature of interactions between fibers and target cells, and the molecular mechanisms leading to tumorigenesis, are not yet understood. Here, the mRNA expression patterns at different stages of asbestos-induced carcinogenesis in rats were monitored by suppression subtractive hybridization (SSH) and array assay. Several genes were upregulated in pretumorous tissues from asbestos-treated rats, in asbestos-induced tumors and in cells treated with asbestos in vitro. The upregulation of the proto-oncogene c-myc, fra-1 and egfr in fiber-induced carcinogenesis was demonstrated at different stages of carcinogenesis. A possible role of Fra-1 as one of the dimeric proteins generating the AP-1 transcription factor was substantiated by its dose-dependent expression in mesothelial cells treated with asbestos in vitro. The upregulation of osteopontin (an extracellular matrix protein) and of zyxin and integrin-linked kinase (intracellular proteins associated with the focal adhesion contact), indicate that fibers may affect integrin-linked signal transduction and extracellular matrix proteins.}, } @article {pmid10773800, year = {2000}, author = {Bisconti, M and Bisetti, A and Bidoli, P}, title = {Malignant mesothelioma in subjects with Marfan's syndrome and Ehlers-Danlos syndrome: only an apparent association?.}, journal = {Respiration; international review of thoracic diseases}, volume = {67}, number = {2}, pages = {223-228}, doi = {10.1159/000029493}, pmid = {10773800}, issn = {0025-7931}, mesh = {Adult ; Biopsy ; Ehlers-Danlos Syndrome/*complications/diagnosis ; Fatal Outcome ; Female ; Genetic Predisposition to Disease ; Humans ; Lip Neoplasms/genetics ; Male ; Marfan Syndrome/*complications/diagnosis ; Mesothelioma/diagnosis/*genetics ; Middle Aged ; Peritoneal Neoplasms/diagnosis/*genetics ; Pleural Neoplasms/diagnosis/*genetics ; }, abstract = {Malignant mesothelioma is a rare neoplasm which could be favored by an hereditary predisposing factor. So far, malignant mesothelioma have never been described in patients with hereditary diseases of the connective tissue. Here, we report some cases of mesothelioma affecting subjects who were not exposed to inhalation of asbestos. One of these subjects was affected by Ehlers-Danlos syndrome, whereas in two brothers, mesothelioma was associated with Marfan's syndrome. The observation of the same histologic subtype of mesothelioma in two brothers and the coexistence of two pathologic conditions of mesodermal origin indicate the presence of hereditary factors predisposing to the cancerogenic action of even small amounts of asbestos. Structural alterations of collagen and primary immunodeficiency may represent the host factor inducing development of the neoplasm. We conclude that the association between these rare disorders of the connective tissue and mesothelioma may not be coincidental, but could be the result of the exposition to small amounts of asbestos in predisposed individuals.}, } @article {pmid10769972, year = {2000}, author = {Kalmaev, KK and Kaptsov, VA}, title = {[Clinical and hygienic aspects of asbestos-induced lung diseases].}, journal = {Gigiena i sanitariia}, volume = {}, number = {2}, pages = {55-57}, pmid = {10769972}, issn = {0016-9900}, mesh = {Asbestos/*adverse effects ; Asbestosis/diagnosis/*etiology/prevention & control ; Bronchitis/diagnosis/etiology/prevention & control ; Humans ; Lung Neoplasms/diagnosis/*etiology/prevention & control ; Mesothelioma/diagnosis/*etiology/prevention & control ; Occupational Diseases/diagnosis/etiology/prevention & control ; Pleural Neoplasms/diagnosis/*etiology/prevention & control ; Silicosis/diagnosis/etiology/prevention & control ; Time Factors ; }, abstract = {The outcomes of 31 operations made in patients with asbestos-induced lung cancer and mesothelioma are considered; the relationships of age, lengths of services, and occupation to the occurrence of diseases are analyzed. A phenomenological concept of development of asbestos-induced cancer diseases is proposed. The functional and morphological features of the course of the disease have been established. Recommendations on the prevention and treatment of abnormalities are given.}, } @article {pmid10761473, year = {2000}, author = {Bakhshandeh, A and Bruns, I and Eberhardt, K and Wiedemann, GJ}, title = {[Chemotherapy in combination with whole-body hyperthermia in advanced malignant pleural mesothelioma].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {125}, number = {11}, pages = {317-319}, doi = {10.1055/s-2007-1024148}, pmid = {10761473}, issn = {0012-0472}, mesh = {Antineoplastic Agents, Alkylating/administration & dosage ; Antineoplastic Agents, Phytogenic/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Carboplatin/administration & dosage ; Combined Modality Therapy ; Etoposide/administration & dosage ; Humans ; Hyperthermia, Induced/*methods ; Ifosfamide/administration & dosage ; Male ; Mesothelioma/diagnosis/*therapy ; Middle Aged ; Palliative Care/methods ; Pleural Effusion, Malignant/diagnosis/therapy ; Pleural Neoplasms/diagnosis/*therapy ; Recurrence ; }, abstract = {HISTORY AND CLINICAL FINDINGS: A 57-year-old man presented with dyspnoea, cough, fatigue and weight loss. He had been exposed to asbestos 30 years ago. Physical examination was unremarkable apart from a suspected pleural effusion.

INVESTIGATIONS: Computed tomography (CT) of the thorax showed multiple pleural masses with pleural effusion on the left side. CT of the abdomen and bronchoscopy were normal. The patient underwent explorative thoracoscopy; biopsies were taken, and diffuse malignant pleural mesothelioma was demonstrated.

TREATMENT AND COURSE: The patient was evaluated at the University Hospital Lübeck for Phase II experimental therapy with whole-body hyperthermia (WBH). The pretreatment evaluation revealed normal cardiorespiratory function and a normal contrast-enhanced CT of the brain. The patient's haematologic profile and electrolytes were normal. The WBH-radiant heat device (RHD) used for therapy was Aquatherm provided by the Cancer Research Institute (CRI, New York, USA). The patient received ifosfamide (5 g/m2, day 1), carboplatin (300 mg/m2, day 1), etoposide (150 mg/m2, days 2-3) combined with WBH at 41.8 degrees C (for 60 minutes). Two cycles were applied without complications and a partial remission of the disease was observed.

CONCLUSION: Radiant heat whole body hyperthermia, in conjunction with a defined anticancer treatment and pharmacological approach to sedation, was a safe and effective palliative treatment in this patient.}, } @article {pmid10744178, year = {2000}, author = {Goldberg, M and Banaei, A and Goldberg, S and Auvert, B and Luce, D and Guéguen, A}, title = {Past occupational exposure to asbestos among men in France.}, journal = {Scandinavian journal of work, environment & health}, volume = {26}, number = {1}, pages = {52-61}, doi = {10.5271/sjweh.510}, pmid = {10744178}, issn = {0355-3140}, mesh = {Adolescent ; Adult ; Age Distribution ; *Asbestos ; Data Collection ; France/epidemiology ; Humans ; Male ; Middle Aged ; *Occupational Exposure ; Socioeconomic Factors ; }, abstract = {OBJECTIVES: This study aimed at reconstructing changes in the frequency and levels of occupational asbestos exposure in France over the past century.

METHODS: Work histories were collected during 11 population-based case-referent studies recently carried out in France, and an asbestos-specific job-exposure matrix including 10 625 jobs was used to estimate indices of past occupational asbestos exposure. The results were estimated from a sample of 4287 subjects, bootstrapped 200 times.

RESULTS: The distribution of socioeconomic categories within the sample was compared with that of the general population in 1954, 1962, 1968, 1975, and 1982. The proportion of blue-collar workers was similar. The highest proportion of exposed subjects was found between 1950 and 1980. Around 10% of each 10-year age class was exposed to asbestos. For those born in 1930-1939, 15.2% was exposed between the ages of 20 and 29 years. For each age class born in 190-1939, the proportion exposed at least once by 60 years of age ranged from 18.2% to 24.5 % and, of those exposed, the cumulative duration of exposure ranged from 11.3 to 15.4 years by the age of 60 years. A population exposure index showed that the heaviest exposure occurred between 1960 and 1970 and that the age classes born between 1920 and 1929 were the most heavily exposed. Time trends showed that the mean value of this index for the men aged 20-59 years reached a peak in the 1960s and then decreased.

CONCLUSIONS: This study presents data of reasonable validity about occupational asbestos exposure in France and its trends over the past century; the data are being used to forecast the development of male mortality from mesothelioma in France.}, } @article {pmid10741273, year = {2000}, author = {O'Byrne, KJ and Dalgleish, AG and Browning, MJ and Steward, WP and Harris, AL}, title = {The relationship between angiogenesis and the immune response in carcinogenesis and the progression of malignant disease.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {36}, number = {2}, pages = {151-169}, doi = {10.1016/s0959-8049(99)00241-5}, pmid = {10741273}, issn = {0959-8049}, mesh = {Disease Progression ; Gene Silencing ; Genes, p53/immunology ; Humans ; Hygiene ; Neoplasms/*blood supply/drug therapy/immunology ; Neovascularization, Pathologic/*etiology/immunology ; Prostaglandin-Endoperoxide Synthases/immunology ; Receptors, Interferon/immunology ; }, abstract = {Recent studies have demonstrated that angiogenesis and suppressed cell-mediated immunity (CMI) play a central role in the pathogenesis of malignant disease facilitating tumour growth, invasion and metastasis. In the majority of tumours, the malignant process is preceded by a pathological condition or exposure to an irritant which itself is associated with the induction of angiogenesis and/or suppressed CMI. These include: cigarette smoking, chronic bronchitis and lung cancer; chronic oesophagitis and oesophageal cancer; chronic viral infections such as human papilloma virus and ano-genital cancers, chronic hepatitis B and C and hepatocellular carcinoma, and Epstein-Barr virus (EBV) and lymphomas; chronic inflammatory conditions such as Crohn's disease and ulcerative colitis and colorectal cancer; asbestos exposure and mesothelioma and excessive sunlight exposure/sunburn and malignant melanoma. Chronic exposure to growth factors (insulin-like growth factor-I in acromegaly), mutations in tumour suppressor genes (TP53 in Li Fraumeni syndrome) and long-term exposure to immunosuppressive agents (cyclosporin A) may also give rise to similar environments and are associated with the development of a range of solid tumours. The increased blood supply would facilitate the development and proliferation of an abnormal clone or clones of cells arising as the result of: (a) an inherited genetic abnormality; and/or (b) acquired somatic mutations, the latter due to local production and/or enhanced delivery of carcinogens and mutagenic growth factors. With progressive detrimental mutations and growth-induced tumour hypoxia, the transformed cell, to a lesser or greater extent, may amplify the angiogenic process and CMI suppression, thereby facilitating further tumour growth and metastasis. There is accumulating evidence that long-term treatment with cyclo-oxygenase inhibitors (aspirin and indomethacin), cytokines such as interferon-alpha, anti-oestrogens (tamoxifen and raloxifene) and captopril significantly reduces the incidence of solid tumours such as breast and colorectal cancer. These agents are anti-angiogenic and, in the case of aspirin, indomethacin and interferon-alpha have proven immunomodulatory effects. Collectively these observations indicate that angiogenesis and suppressed CMI play a central role in the development and progression of malignant disease.}, } @article {pmid10730473, year = {1999}, author = {Merler, E and Lagazio, C and Biggeri, A}, title = {[Trends in mortality from primary pleural tumor and incidence of pleural mesothelioma in Italy: a particularly serious situation].}, journal = {Epidemiologia e prevenzione}, volume = {23}, number = {4}, pages = {316-326}, pmid = {10730473}, issn = {1120-9763}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Incidence ; Italy/epidemiology ; Male ; Mesothelioma/*mortality ; Middle Aged ; Pleural Neoplasms/*mortality ; Time Factors ; }, abstract = {We present: a) an analysis of the past mortality from Primary Pleural Tumors (PPT) occurred in Italy between 1968 and 1992 by an age-cohort-period model, using a Poisson regression model, estimating the risk of dying by birth cohort, the Lifetime Cumulative risk (25-84 years) by birth cohort, the risk by calendar period and testing the full model (age-cohort-period effects); b) a summary of the incidence of mesothelioma as recorded in Italy by Cancer Registries and Mesothelioma Registries. The highest Lifetime Cumulative Risk of dying from TTP is recorded for the birth cohort 1946-'50 (6.2 per thousand among males, 1.64 among females). Whereas the risk by birth cohort becomes flat among females born after 1936, among males the risk is increasing up to the youngest birth cohorts. By calendar period, the highest risk of dying is observed in the last period (1991-'92). The inclusion in the full model of the calendar period term increases significantly the goodness-of-fit of the model among females, but not among males. The highest incidence of mesothelioma in both genders registered by 150 Cancer Registries all over the world is currently recorded among the population of Genoa and Trieste, where large ship-building plants are located. Even higher incidence mesothelioma rates have been recently recorded in other areas of Italy. The trend in PPT mortality in Italy could have been influenced, but not explained, by the increased awareness over time of the disease, but it fits well with the pattern occurring in most industrialized countries of western Europe, with the unprotected industrial use of asbestos which occurred in Italy, and also with the gender characteristics of the work-force employed in asbestos-exposing activities. A ban of asbestos use has been introduced in Italy in 1992. However, considering that asbestos seems to act as an initiator for mesothelioma, the trend in male mortality for PPT will not peak until two or three decades.}, } @article {pmid10730472, year = {1999}, author = {Ivaldi, C and Dalmasso, P and Nesti, M and Magnani, C}, title = {[Malignant Mesothelioma Registry from Piedmont. Incidence in 1990-1995].}, journal = {Epidemiologia e prevenzione}, volume = {23}, number = {4}, pages = {308-315}, pmid = {10730472}, issn = {1120-9763}, mesh = {Female ; Humans ; Incidence ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology ; Peritoneal Neoplasms/*epidemiology ; Pleural Neoplasms/*epidemiology ; *Registries ; }, abstract = {This paper describes methods and results of the Piedmont Malignant Mesothelioma Registry. The Registry is active since 1990 and collects all histologically confirmed incident cases of malignant mesothelioma (m.m.) occurring in the residents of Piedmont. In the period 1990-95, 346 cases of pleural m.m. (211 males and 135 females) and 41 (28 males and 13 females) of peritoneal m.m. have been observed. Amongst the inhabitants of the Local Health Authority of Casale Monferrato, where manufacturing of cement asbestos has determined serious asbestos exposures both in the work place and general environment, there have been 105 pleural m.m. and 17 peritoneal m.m. (incidence rate were 15.6 for men and 13.0 for women and 3.6 for men and 0.6 for women respectively). Leaving out the Local Health Authority (LHA) of Casale Monferrato, the annual incidence rate in Piedmont (for 10(5) person-years, age standardised on the 1981 Italian population), has been 1.0 in men and 0.6 in women for the pleural m.m. (respectively 154 and 87 cases) and 0.09 and 0.06 for peritoneal m.m. (14 and 10 cases). Possible cases of m.m. (cytological and/or x-ray diagnosis) have been searched in the file of hospital admission and discharges (SDO) in 1994-95: 46 additional cases were found, with a 25% increase in incidence rates. The analysis of incidence according to geographical aggregations (defined according to the LHA borders) has identified, besides some already known important sources of exposures, as Casale Monferrato and the LHA of Lanzo (Balangero mine), other areas with excess of incidence as the LHA's of Galliate and Caluso which show an increased incidence of pleural m.m. in men or Vercelli and Chieri with increased incidence of pleural m.m. in women. These observation deserves further analysis.}, } @article {pmid10730138, year = {1999}, author = {Wang, E and Dement, JM and Lipscomb, H}, title = {Mortality among North Carolina construction workers, 1988-1994.}, journal = {Applied occupational and environmental hygiene}, volume = {14}, number = {1}, pages = {45-58}, doi = {10.1080/104732299303412}, pmid = {10730138}, issn = {1047-322X}, support = {U02/CCU312014//PHS HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; *Cause of Death ; *Facility Design and Construction ; Humans ; Industry ; Lung Diseases/etiology/mortality ; Male ; Middle Aged ; Mortality/*trends ; North Carolina/epidemiology ; Occupational Health/*statistics & numerical data ; Risk Assessment ; }, abstract = {This study evaluated proportionate mortality patterns among all male construction workers in North Carolina who resided and died in North Carolina during the period 1988-1994. Proportionate Mortality Ratios (PMRs) and Proportionate Cancer Mortality Ratios (PCMRs) compared the number of deaths among male construction workers with the number of deaths expected based on the gender, race, and cause-specific mortality experience of the entire North Carolina population by five-year age groups for the same years of study. PMRs based on United States death rates also were calculated. Among all male construction workers, significantly elevated mortality was observed for several causes possibly related to work including malignant neoplasms of buccal cavity (PMR = 143), pharynx (PMR = 134), and lung (PMR = 113), pneumoconiosis (PMR = 111), transportation accidents (PMR = 106), and accidental falls (PMR = 132). Elevated mortality also was observed for causes more related to lifestyle and non-occupational factors including alcoholism (PMR = 145), cirrhosis of the liver (PMR = 129), accidental poisoning (PMR = 136), and homicide (PMR = 141). Patterns of elevated mortality for Whites and Black men were similar and PCMR mortality patterns for Blacks and Whites combined were similar to PMRs. Construction workers were at significantly increased risk for deaths resulting from falls from ladders or scaffolds, falls from or out of buildings or structures, and electrocutions. Construction trades found to have statistically elevated cancer risks include laborers and roofers (buccal cavity), painters (pharynx), laborers (peritoneum), and carpenters, painters, brick masons, and operating engineers (lung). These data are consistent with other reports demonstrating excess mortality from asbestos-related diseases (pneumoconiosis, lung cancer, and mesothelioma) among construction workers. Dry-wall workers and laborers were found to have a statistically elevated risk of death as a result of respiratory tuberculosis.}, } @article {pmid10723045, year = {2000}, author = {Jemal, A and Grauman, D and Devesa, S}, title = {Recent geographic patterns of lung cancer and mesothelioma mortality rates in 49 shipyard counties in the United States, 1970-94.}, journal = {American journal of industrial medicine}, volume = {37}, number = {5}, pages = {512-521}, doi = {10.1002/(sici)1097-0274(200005)37:5<512::aid-ajim7>3.0.co;2-m}, pmid = {10723045}, issn = {0271-3586}, mesh = {Age Factors ; Asbestos/adverse effects ; Atlantic Ocean ; Bronchial Neoplasms/mortality ; Female ; Humans ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; Occupational Diseases/*mortality ; Occupational Exposure/adverse effects ; Pacific Ocean ; Pleural Neoplasms/*mortality ; Risk Factors ; Rural Health/statistics & numerical data ; Sex Factors ; *Ships ; Smoking/epidemiology ; Tracheal Neoplasms/mortality ; United States/epidemiology ; Urban Health/statistics & numerical data ; White People ; }, abstract = {BACKGROUND: Lung cancer mortality rates among white males in the United States were observed to be elevated during 1950-69 in counties with shipbuilding industries during World War II; risk was found to be associated with asbestos exposure. We evaluated the geographic patterns in more recent years, 1970-94, for whites and compared them with the 1950-69 patterns.

METHODS: We calculated age-adjusted rates and estimated rate ratios between comparison groups.

RESULTS: Rates generally were higher in shipyard counties than in all nonshipyard counties and in coastal nonshipyard counties for both sexes and time periods. Rates increased markedly from 1950-69 to 1970-94 in all groups, with the changes more pronounced in females than males. Pleural mesothelioma mortality rates were also significantly higher in shipyard counties than coastal nonshipyard counties in all regions among males but not among females.

CONCLUSIONS: The more pronounced changes in lung cancer mortality rates among females in shipyard counties may be attributed to the combined effects of low asbestos exposures and changes in smoking behavior. Am. J. Ind. Med. 37:512-521, 2000. Published 2000 Wiley-Liss, Inc.}, } @article {pmid10707363, year = {2000}, author = {Kayser, K and Seemann, C and André, S and Kugler, C and Becker, C and Dong, X and Kaltner, H and Gabius, HJ}, title = {Association of concentration of asbestos and asbestos-like fibers with the patient's survival and the binding capacity of lung parenchyma to galectin-1 and natural alpha-galactoside- and alpha-mannoside-binding immunoglobulin G subfractions from human serum.}, journal = {Pathology, research and practice}, volume = {196}, number = {2}, pages = {81-87}, doi = {10.1016/s0344-0338(00)80037-0}, pmid = {10707363}, issn = {0344-0338}, mesh = {Adult ; Asbestos/*metabolism ; Asbestosis/metabolism/*mortality/pathology ; *Cell Cycle Proteins ; Female ; Galactosides/immunology/*metabolism ; Galectin 1 ; Hemagglutinins/immunology/*metabolism ; Humans ; Immunoenzyme Techniques ; Immunoglobulin G/immunology/*metabolism ; Lung/metabolism/pathology/surgery ; Lung Neoplasms/metabolism/*mortality/pathology ; Male ; Mannosides/immunology/*metabolism ; Mesothelioma/metabolism/*mortality/pathology ; Middle Aged ; Mineral Fibers ; Pulmonary Alveoli/metabolism/pathology ; S100 Calcium Binding Protein A6 ; S100 Proteins/immunology/metabolism ; Survival Rate ; }, abstract = {Our aim in this study was to search for lung parenchyma alterations associated with asbestos and/or asbestos-like fiber concentration. This was done by means of immuno- or glycohistochemistry. The hot-ashing technique determined the asbestos and asbestos-like fiber concentrations in the lung tissues of 100 patients of whom 52 were treated for primary lung and 25 for secondary lung tumors; fiber concentration was also measured for 23 patients whose disease was benign. The results were correlated to smoking habits, survival of the patients, and expression of binding capacities for endogenous lectins, natural carbohydrate-binding and lectin-specific antibodies. The cohort with proven asbestos exposure revealed a mean fiber concentration 114 f/g compared to 95 f/g in the non-exposed group. An increased asbestos fiber concentration was correlated to galectin-1-binding and the presence of epitopes for natural immunoglobulin G subfractions with selectivity to alpha-galactosides and alpha-mannosides. The survival of patients with primary and secondary lung tumors was negatively associated with the fiber concentration. The data indicate that increased presence of asbestos is correlated with an alteration of defined glycohistochemical features of alveolar lining cells.}, } @article {pmid10703192, year = {1999}, author = {Barbieri, PG and Migliori, M and Merler, E}, title = {[The incidence of malignant mesothelioma (1977-1996) and asbestos exposure in the population of an area neighboring Lake Iseo, northern Italy].}, journal = {La Medicina del lavoro}, volume = {90}, number = {6}, pages = {762-775}, pmid = {10703192}, issn = {0025-7818}, mesh = {Age Distribution ; Aged ; Asbestos/*adverse effects ; Carcinogens/*adverse effects ; Female ; Fresh Water ; Humans ; Incidence ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Morbidity/trends ; Occupational Exposure/*adverse effects/statistics & numerical data ; Peritoneal Neoplasms/*epidemiology/etiology ; Pleural Neoplasms/*epidemiology/etiology ; Retrospective Studies ; Sex Distribution ; }, abstract = {The study was stimulated by the occurrence of malignant mesotheliomas among the workers of two adjacent factories located in Sarnico, near Lake Iseo (province of Brescia, northern Italy), one of which manufactured crocidolite and chrysotile ropes and gaskets until 1993. The aim of the study was: identification of malignant mesotheliomas occurring between 1977 and 1996 among the residents of 11 villages, which constituted the recruitment area of the work-force; estimation of the incidence of malignant pleural mesothelioma; collection of working histories of all cases to evaluate previous exposure to asbestos and radiation therapy. 21 cases of mesothelioma were detected (20 pleural, 1 peritoneal; 9 among males), and 20 were supported by histopathologic diagnosis. The incidence (x 100,000 person-years, standard: European population) was 2.5 (0.7-4.2) and 2.8 (1.2-4.3) among males and females, respectively, corresponding to a three-fold increase among males and a more than ten fold increase among women in comparison with the incidence reported by the Lombardy Cancer Registry. No cases had been exposed to radiation therapy, whereas all cases had been occupationally exposed to asbestos. Occupational exposure to asbestos had occurred in work on the production of crocidolite and chrysotile ropes and gaskets (6 males); in work in a textile factory producing cotton garments that was adjacent to and polluted by the former, where, in addition, chrysotile blankets were used for fireproofing in the weaving area and pipes were insulated using amosite-containing materials (10 cases, 6 among females); 5 cases occurred among women working in silk factories, where asbestos exposure was possible because of the presence of pipes insulated with asbestos and because women were handling temperature-controlled trays insulted with asbestos. In conclusion, the study demonstrated that the occurrence of mesothelioma was higher among females than males in the study area and that all cases of mesotheliomas had been occupationally exposed to asbestos.}, } @article {pmid10683983, year = {1998}, author = {Luo, S and Zhang, Y and Mu, S and Zhang, C and Ma, T and Liu, X}, title = {[The risk of lung cancer and mesothelioma in farmers exposed to crocidolite in environment].}, journal = {Hua xi yi ke da xue xue bao = Journal of West China University of Medical Sciences = Huaxi yike daxue xuebao}, volume = {29}, number = {1}, pages = {63-65}, pmid = {10683983}, issn = {0257-7712}, mesh = {Adult ; Aged ; Asbestos, Crocidolite/*adverse effects ; China/epidemiology ; Cohort Studies ; *Environmental Exposure ; Female ; Humans ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; Middle Aged ; Retrospective Studies ; Risk Factors ; }, abstract = {To assess the risk of lung cancer and mesothelioma after environmental exposure to crocidolite for 20-30 years, a retrospective cohort study was carried out in farmers who had been exposed to crocidolite in environment. 1610 subjects were followed up for 9 years (Jan. 1, 1987 Dec. 31, 1995). The control group consisted of 7646 farmers who resided in the noncrocidolite pollution rural area in the same province. The results showed that the annual mortality rate was 43.75 per 100,000 population for lung cancer, and 36.46 per 100,000 for mesothelioma. Significantly high risks of lung cancer (RR 5.67) and mesothelioma (RR 182.3) were noted. These results demonstrate a strong causal association between lung cancer, mesothelioma and exposure to crocidolite.}, } @article {pmid10683950, year = {1997}, author = {Lin, F and Zhai, C and Liu, Y and Zhou, G and Sun, Z and Li, S}, title = {[p53 gene mutations in BALB/c 3T3 cells transformed by crocidolite].}, journal = {Hua xi yi ke da xue xue bao = Journal of West China University of Medical Sciences = Huaxi yike daxue xuebao}, volume = {28}, number = {4}, pages = {375-379}, pmid = {10683950}, issn = {0257-7712}, mesh = {3T3 Cells ; Animals ; Asbestos, Crocidolite/*toxicity ; Cell Line, Transformed ; Cell Transformation, Neoplastic ; Exons ; *Genes, p53 ; Mice ; Mice, Inbred BALB C ; *Mutation ; Polymerase Chain Reaction ; Polymorphism, Single-Stranded Conformational ; }, abstract = {This study sought to address the relationship between crocidolite and p53 gene mutation. The mutations of p53 gene in 8 BALB/c 3T3 cell lines transformed by crocidolite were analysed. Altogether 11 exons of the gene from 8 cell lines were detected by PCR-SSCP. 7 alterations were found; 2 of them were located in exon 4-6, and 5 in 9-11. Most of the mutations (5/7) were of one more band than that of wild cell from SSCP, and alterations were randomly scattered among the crocidolite doses groups. The results suggest that the presence of a p53 alteration is not related to the dose of crocidolite used. Besides, p53 mutation may occur in a relatively later period of the growth of the transformed cell lines. The results also showed that the mutations occurred predominantly in exons 9-11. This was different from that seen in human mesothelioma where mutations in the exon 5-8 of p53 gene were more frequently observed.}, } @article {pmid10680897, year = {2000}, author = {Shanks, JH and Harris, M and Banerjee, SS and Eyden, BP and Joglekar, VM and Nicol, A and Hasleton, PS and Nicholson, AG}, title = {Mesotheliomas with deciduoid morphology: a morphologic spectrum and a variant not confined to young females.}, journal = {The American journal of surgical pathology}, volume = {24}, number = {2}, pages = {285-294}, doi = {10.1097/00000478-200002000-00015}, pmid = {10680897}, issn = {0147-5185}, mesh = {Aged ; Biomarkers, Tumor/analysis ; Decidua/chemistry/*pathology ; Female ; Humans ; Immunoenzyme Techniques ; Male ; Mesothelioma/chemistry/*pathology ; Microvilli/ultrastructure ; Middle Aged ; Peritoneal Neoplasms/chemistry/*pathology ; Pleural Neoplasms/chemistry/*pathology ; }, abstract = {Deciduoid mesotheliomas are rare with only four previously reported cases, all affecting the peritoneum of young females. We describe another six cases (three men and three women; age range 52-65 yrs, median 55 yrs; five peritoneal and one pleural). Three patients had an occupational history of asbestos exposure. The deciduoid appearance predominated in four cases, whereas in two it represented a minor component within conventional tubulopapillary epithelioid mesothelioma. All tumors were strongly cytokeratin-positive (including CK5/6) and all showed at least focal staining for thrombomodulin, HBME-1, and calretinin. All were negative for epithelial mucin (D/PAS), CEA, BerEP4, LeuM1 (CD15), CD21, CD35, and S100 protein. Five of six cases (83%) were vimentin-positive and two (33%) were focally positive for alpha-smooth muscle actin. A differential diagnosis of gastrointestinal autonomic nerve tumor (GANT) had been initially considered from the morphology of one case, and we found positivity for some of the "neuronal" markers described in GANTs. This prompted us to apply such a panel to the other five tumors, accepting that the cytokeratin positivity encountered in all of our cases would exclude GANT. All cases of deciduoid mesothelioma (100%) were positive for PGP 9.5 and NSE and four of six (66%) were positive for NKI/C3. Weak focal staining (<5% cells) for synaptophysin was seen in two of six tumors. All cases were chromogranin-negative. All cases examined by electron microscopy showed desmosomes and smooth microvilli without rootlets but no neuroendocrine granules. In conclusion, a deciduoid morphology appears to be part of the histopathologic spectrum encountered in epithelioid mesothelioma. This variant is not confined to female patients and occurs over a wider age range than previously recognized. The overlapping immunophenotype with GANTs illustrates that caution should be exercised when interpreting positivity for "neuronal" markers in this context. An immunohistochemical panel that includes cytokeratins should always be used.}, } @article {pmid10670550, year = {2000}, author = {Luce, D and Bugel, I and Goldberg, P and Goldberg, M and Salomon, C and Billon-Galland, MA and Nicolau, J and Quénel, P and Fevotte, J and Brochard, P}, title = {Environmental exposure to tremolite and respiratory cancer in New Caledonia: a case-control study.}, journal = {American journal of epidemiology}, volume = {151}, number = {3}, pages = {259-265}, doi = {10.1093/oxfordjournals.aje.a010201}, pmid = {10670550}, issn = {0002-9262}, mesh = {Adolescent ; Adult ; Asbestos, Amphibole/*adverse effects ; Case-Control Studies ; Environmental Exposure/*adverse effects ; Female ; France ; Humans ; Male ; Mesothelioma/chemically induced/epidemiology ; Respiratory Tract Neoplasms/*chemically induced/*epidemiology ; }, abstract = {A case-control study on respiratory cancers was conducted in New Caledonia (South Pacific), where a high incidence of malignant pleural mesothelioma had been observed. The disease pattern suggested an environmental exposure to asbestos. The first results showed that, in some areas, tremolite asbestos derived from local outcroppings was used as whitewash (locally named "pö"). All cases diagnosed between 1993 and 1995 (including 15 pleural mesotheliomas, 228 lung cancers, and 23 laryngeal cancers) and 305 controls were included in the study. Detailed information on past or present use of the whitewash, residential history, smoking, diet, and occupation was collected. The risk of mesothelioma was strongly associated with the use of the whitewash (odds ratio (OR) = 40.9; 95% confidence interval (CI): 5.15, 325). All Melanesian cases had been exposed. Among Melanesian women, exposure to the whitewash was associated with an increased risk of lung cancer (OR = 4.89; 95% CI: 1.13, 21.2), and smokers exposed to po had an approximately ninefold risk (OR = 9.26; 95% CI: 1.72, 49.7) compared with women who never smoked and had never used the whitewash. In contrast, no association was noted between exposure to pö and lung cancer risk among Melanesian men, probably because of lower exposure levels. Among non-Melanesians, the numbers of exposed subjects were too small to assess the effect of exposure to po. There was no indication of elevated risks for the other cancer sites.}, } @article {pmid10669695, year = {2000}, author = {Dodson, RF and O'Sullivan, MF and Huang, J and Holiday, DB and Hammar, SP}, title = {Asbestos in extrapulmonary sites: omentum and mesentery.}, journal = {Chest}, volume = {117}, number = {2}, pages = {486-493}, doi = {10.1378/chest.117.2.486}, pmid = {10669695}, issn = {0012-3692}, mesh = {Aged ; Asbestos/analysis ; Asbestosis/*pathology ; Humans ; Lung/pathology ; Lung Neoplasms/*pathology ; Male ; Mesentery/*pathology ; Mesothelioma/*pathology ; Microscopy, Electron ; Middle Aged ; Omentum/*pathology ; Peritoneal Neoplasms/*pathology ; Pleura/pathology ; Pleural Neoplasms/*pathology ; }, abstract = {STUDY OBJECTIVES: Asbestos fibers have not been reported in tissues from the peritoneal cavity. Therefore, omentum, mesentery, and lung tissues from 20 individuals in whom mesothelioma was diagnosed were analyzed for asbestos bodies and asbestos fibers.

DESIGN: Tissue was digested and prepared filters were analyzed by light microscopy and analytical transmission electron microscopy.

RESULTS: Asbestos bodies were found in the lungs of 18 individuals, mesentery samples from 5, and omentum samples from 2. Uncoated asbestos fibers were found in lungs of 19 patients, 17 of whom had fibers in at least one extrapulmonary site. The most common asbestos in the omentum and mesentery was amosite. Several features of asbestos found in lung influenced the likelihood of amphibole fibers being found in the omentum or mesentery. Lung features included total amphibole fiber burden, length, aspect ratio, and ferruginous body burden. An increased total ferruginous body burden was strongly associated with increased likelihood of detecting amphiboles in the omentum (p < 0. 05).

CONCLUSION: Asbestos fibers reach areas in the peritoneal cavity where some mesotheliomas develop. This study suggests their presence can be predicted based on concentrations and characteristics of fiber burdens in lung tissue.}, } @article {pmid10667164, year = {2000}, author = {Ansari, NA and Derias, NW}, title = {Diagnosis of malignant mesothelioma by fine needle aspiration of a cervical lymph node. A case report.}, journal = {Acta cytologica}, volume = {44}, number = {1}, pages = {70-74}, doi = {10.1159/000326229}, pmid = {10667164}, issn = {0001-5547}, mesh = {Adenocarcinoma/chemistry/diagnosis ; Aged ; Biomarkers, Tumor/analysis ; *Biopsy, Needle ; Diagnosis, Differential ; Fatal Outcome ; Humans ; Immunohistochemistry ; Lymph Nodes/chemistry/*pathology ; Lymphatic Metastasis ; Male ; Mesothelioma/chemistry/*diagnosis/secondary ; Pleural Neoplasms/chemistry/*diagnosis ; }, abstract = {BACKGROUND: Clinically documented distant metastases are rare in mesothelioma and tend to occur late in the course of the disease, well after the diagnosis has been made. In this instance, diagnosis was not made until a metastatic deposit was identified microscopically in the enlarged lymph node.

CASE: A 65-year-old male with no definite history of occupational asbestos exposure presented with chest pain, pleural effusion and supraclavicular lymphadenopathy. Cytologic examination of material obtained by fine needle aspiration from his cervical lymph node revealed malignant mesothelioma. This was confirmed on histology.

CONCLUSION: This was a particularly rare presentation and, as far as we are aware, was the first case in which mesothelioma was diagnosed by fine needle aspiration of a cervical lymph node. It serves to remind the pathologist that when confronted with a lymph node involved by tumor, the possibility of mesothelioma should be included in the differential diagnosis. The case also demonstrates the usefulness of fine needle aspiration in the diagnosis of metastatic tumor.}, } @article {pmid10665909, year = {2000}, author = {Zhang, PJ and Livolsi, VA and Brooks, JJ}, title = {Malignant epithelioid vascular tumors of the pleura: report of a series and literature review.}, journal = {Human pathology}, volume = {31}, number = {1}, pages = {29-34}, doi = {10.1016/s0046-8177(00)80194-x}, pmid = {10665909}, issn = {0046-8177}, mesh = {Adult ; Aged ; Antigens, CD34/metabolism ; Factor VIII/metabolism ; Female ; Hemangiosarcoma/*metabolism/*pathology ; Humans ; Male ; Middle Aged ; Platelet Endothelial Cell Adhesion Molecule-1/metabolism ; Pleural Neoplasms/*metabolism/*pathology ; }, abstract = {Primary malignant vascular tumors of the pleura are rare. The significance and difficulty of distinction between pleural epithelioid hemangioendothelioma (EHE) and angiosarcoma have not yet been addressed. A new series of pleural angiosarcoma is reported, and the relevant literature is reviewed. Five cases were identified from files of the authors' institutions and personal consultation cases (J.J.B.). Twenty-six cases of primary malignant vascular tumors of the pleura were identified in the literature. In a total of 31 cases, 22 were from the West and 9 from Japan. Patients were 22 to 79 years old (average, 57), and the male/female ratio was 9:1. Prior chronic pyothorax was identified only in cases reported from Japan. History of exposure to radiation or asbestos was noted in a few Western cases. The most common presentation was pleural thickening and effusion. Almost all of the patients died of disease shortly after diagnosis. A spectrum of histology ranging from characteristic high-grade epithelioid to relatively low-grade EHE-like features was observed in our cases and can be found in previous reports. Most cases showed variable spotty cytokeratin immunoreactivity. Endothelial markers (factor 8, CD34, or CD31) were invariably positive. Pleural angiosarcomas are often epithelioid and can be easily mistaken for mesothelioma or carcinoma clinically and histologically. Awareness of this rare tumor should prompt the use of endothelial markers when faced with a questionable mesothelioma. When cytokeratin is negative, or focal with strong vimentin reactivity, a vascular tumor should be suspected and confirmed with vascular markers. Because of their invariably aggressive behavior, all epithelioid vascular tumors of the pleura should be considered highly malignant regardless of the presence of EHE-like histological features.}, } @article {pmid10661015, year = {1999}, author = {Gupta, N}, title = {Malignant pleural mesothelioma without asbestos exposure.}, journal = {The Indian journal of chest diseases & allied sciences}, volume = {41}, number = {4}, pages = {244-245}, pmid = {10661015}, issn = {0377-9343}, mesh = {Adult ; Female ; Humans ; Mesothelioma/*diagnostic imaging ; Pleural Neoplasms/*diagnostic imaging ; *Tomography, X-Ray Computed ; }, } @article {pmid10660089, year = {1999}, author = {Kleymenova, EV and Horesovsky, G and Pylev, LN and Everitt, J}, title = {Mesotheliomas induced in rats by the fibrous mineral erionite are independent from p53 alterations.}, journal = {Cancer letters}, volume = {147}, number = {1-2}, pages = {55-61}, doi = {10.1016/s0304-3835(99)00275-x}, pmid = {10660089}, issn = {0304-3835}, mesh = {Animals ; Carcinogenicity Tests ; DNA Mutational Analysis ; Immunohistochemistry ; Male ; Mesothelioma/chemically induced/*genetics/pathology ; Peritoneal Neoplasms/chemically induced/*genetics/pathology ; RNA/isolation & purification ; Rats ; Rats, Wistar ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Analysis, DNA ; Tumor Cells, Cultured ; Tumor Suppressor Protein p53/biosynthesis/*genetics ; Zeolites ; }, abstract = {The development of human malignant mesothelioma (MM) is strongly associated with occupational or environmental exposure to certain natural mineral fibers, although the genetic mechanisms underlying this malignancy remain unclear. Although the p53 gene is frequently mutated in various tumors, human asbestos-associated MMs appear to develop independently from p53 alterations. The high mesotheliomagenic potency of natural fibrous mineral erionite is well established in humans and rodents, but no data regarding genetic alterations in erionite-associated tumors are currently available. Previous speculations that the oncogenic mechanisms underlying asbestos and erionite carcinogenesis may differ led us to examine whether the p53 gene is targeted in erionite carcinogenesis. Fifteen erionite-induced rat MMs as well as six cell lines derived from asbestos-induced and spontaneous rat MM were analyzed for p53 mutations by direct DNA sequencing and immunohistochemical analysis. Both approaches did not reveal p53 alterations in rat MM samples used in the study indicating that, similar to asbestos carcinogenesis, erionite carcinogenesis does not target the p53 tumor suppressor gene.}, } @article {pmid10656689, year = {2000}, author = {Murthy, SS and Shen, T and De Rienzo, A and Lee, WC and Ferriola, PC and Jhanwar, SC and Mossman, BT and Filmus, J and Testa, JR}, title = {Expression of GPC3, an X-linked recessive overgrowth gene, is silenced in malignant mesothelioma.}, journal = {Oncogene}, volume = {19}, number = {3}, pages = {410-416}, doi = {10.1038/sj.onc.1203322}, pmid = {10656689}, issn = {0950-9232}, support = {CA-06927/CA/NCI NIH HHS/United States ; CA-45745/CA/NCI NIH HHS/United States ; }, mesh = {Alleles ; Animals ; Cell Line ; DNA Methylation ; DNA, Complementary/analysis ; Down-Regulation ; Female ; Glypicans ; *Heparan Sulfate Proteoglycans ; Heparitin Sulfate/*genetics ; Humans ; Mesothelioma/*genetics/pathology ; Promoter Regions, Genetic ; Proteoglycans/*genetics ; Rats ; Rats, Inbred F344 ; }, abstract = {Gene expression changes in rat asbestos-induced malignant mesothelioma (MM) cells were investigated by differential mRNA display. A mRNA transcript identified by this approach was abundant in normal rat mesothelial cells but not expressed in rat MM cell lines. Northern blot analysis confirmed that this transcript is uniformly silenced in rat MM cell lines and primary tumors. Nucleotide sequence analysis revealed that this transcript is encoded by the rat glypican 3 gene (GPC3), whose human homolog is mutated in the Simpson-Golabi-Behmel overgrowth syndrome. Allelic loss at the GPC3 locus was infrequent (6.9%) in MM cell lines, and no mutations were found. GPC3 transcript levels were markedly decreased in 16 of 18 primary tumors and 17 of 22 human MM cell lines. Most of the cell lines were shown to have aberrant methylation of the GPC3 promoter region. In two of four human MM cell lines tested, GPC3 expression was restored after 2-deoxy 5-azacytidine (DAC)-mediated demethylation of its promoter region. Ectopic expression of GPC3 inhibited in vitro colony formation of human MM cells. Collectively, these data suggest that down-regulation of GPC3 is a common occurrence in MM and that GPC3, an X-linked recessive overgrowth gene, may encode a negative regulator of mesothelial cell growth.}, } @article {pmid10652684, year = {2000}, author = {Froom, P and Lahat, N and Kristal-Boneh, E and Cohen, C and Lerman, Y and Ribak, J}, title = {Circulating natural killer cells in retired asbestos cement workers.}, journal = {Journal of occupational and environmental medicine}, volume = {42}, number = {1}, pages = {19-24}, doi = {10.1097/00043764-200001000-00007}, pmid = {10652684}, issn = {1076-2752}, mesh = {Aged ; Asbestos/*adverse effects/immunology ; Carcinogens/*adverse effects ; Case-Control Studies ; Humans ; Killer Cells, Natural/*immunology ; Male ; Middle Aged ; *Occupational Exposure ; Retirement ; Risk Assessment ; Time Factors ; }, abstract = {The effect of past exposure to asbestos on natural killer (NK) cell number and activity is uncertain. We measured NK cell number and activity in 1052 retired asbestos workers without symptomatic lung disease, lung cancer, or mesothelioma and with a long latency period from exposure; results were compared with those for 100 healthy age-matched controls. The exposed workers showed a decreased NK cell activity and increased NK cell number, yielding a 10.8 higher odds ratio for low NK activity per cell compared with controls (95% confidence interval 6.4 to 18.4), which was due to both a decrease in NK cell activity and an increase in NK cell number. Asbestos exposure of 10 years or more increased the risk of low NK activity per cell. We conclude that exposure to asbestos is associated with diminished effectiveness of NK cells and a concomitant increase in the number of NK circulating cells.}, } @article {pmid10642419, year = {2000}, author = {Kishimoto, T and Morinaga, K and Kira, S}, title = {The prevalence of pleural plaques and/or pulmonary changes among construction workers in Okayama, Japan.}, journal = {American journal of industrial medicine}, volume = {37}, number = {3}, pages = {291-295}, doi = {10.1002/(sici)1097-0274(200003)37:3<291::aid-ajim7>3.0.co;2-a}, pmid = {10642419}, issn = {0271-3586}, mesh = {Asbestosis/*epidemiology ; Construction Materials/*adverse effects ; Humans ; Japan/epidemiology ; Lung Diseases/*chemically induced/epidemiology ; Occupational Exposure/*adverse effects ; Pleural Diseases/*chemically induced/epidemiology ; Prevalence ; Radiography, Thoracic ; Tomography, X-Ray Computed ; }, abstract = {BACKGROUND: Since asbestos has been widely used in Japanese building materials since 1960s, a large number of Japanese construction workers may be exposed to asbestos occupationally.

METHODS: Among 2951 construction workers in Okayama, Japan, the prevalence of asbestos-induced pleural or pulmonary changes was examined by screening chest x-rays; these findings were confirmed by computed tomography (CT) scanning of the chest.

RESULTS: Among 2951 construction workers, 168 (5.7%) were found to have significant findings for pleural plaque or pulmonary changes on chest x-ray. Seventy-four had both pleural plaque and asbestosis, 85 pleural plaques alone, and 9 asbestosis alone. In 11 subjects, pleural plaques were suggested by chest x-ray, but neither pleural plaque nor asbestosis was demonstrated by chest CT. Honeycombing as one of the characteristic findings of asbestosis was found in 29 subjects. Others showed subpleural spots or curvilinear shadow, which suggested the early stage of asbestosis. The occupations of these workers were carpenters (64), plasterers (27), and concrete board cutters (14). About 30% of the workers with these findings were aware that they were handling asbestos in activities such as installation of asbestos boards, and/or asbestos spraying.

CONCLUSIONS: As the incidence of malignant mesothelioma and primary lung cancer associated with asbestos exposure are high, screening by chest CT is necessary for detecting asbestos-induced pulmonary and/or pleural lesions. Education for protection such as telling about the presence of asbestos in building materials is also necessary.}, } @article {pmid10642417, year = {2000}, author = {Gennaro, V and Finkelstein, MM and Ceppi, M and Fontana, V and Montanaro, F and Perrotta, A and Puntoni, R and Silvano, S}, title = {Mesothelioma and lung tumors attributable to asbestos among petroleum workers.}, journal = {American journal of industrial medicine}, volume = {37}, number = {3}, pages = {275-282}, doi = {10.1002/(sici)1097-0274(200003)37:3<275::aid-ajim5>3.0.co;2-i}, pmid = {10642417}, issn = {0271-3586}, mesh = {Asbestos/*adverse effects ; Data Interpretation, Statistical ; Female ; Humans ; Italy/epidemiology ; Lung Neoplasms/*chemically induced/epidemiology ; Male ; Mesothelioma/*chemically induced/epidemiology ; Occupational Diseases/mortality ; *Occupational Exposure ; Petroleum/*adverse effects ; Pleural Neoplasms/chemically induced/epidemiology ; Smoking/adverse effects ; }, abstract = {BACKGROUND: Asbestos exposure has been definitively found to be associated with both mesothelioma and lung cancer. Nevertheless, in the overall population of oil refinery workers potentially exposed to asbestos, many studies clearly show a definitely increased risk of mesothelioma, but no proven excess of lung cancer after comparison to the general population. Through the presentation of new data and the re-appraisal of two recent and independent epidemiological studies conducted in Liguria, Italy, and Ontario, Canada, we attempt to shed light on this apparently paradoxical finding.

METHODS: Lung cancer mortality was studied among maintenance workers exposed to asbestos, and among two other subgroups of refinery employees: blue collar and white collar workers. The comparison with blue collar workers was performed in order to take into account the role of healthy worker effect, smoking habit, and the socioeconomic level. The comparison with white collar workers was performed to control for other occupational lung carcinogens.

RESULTS AND CONCLUSIONS: Results reveal a consistency between the two studies and show that 96-100% of the mesotheliomas and 42-49% of the lung tumors arising among maintenance workers were attributable to asbestos exposure. Our new analysis, estimating two cases of asbestos-related lung cancer for each case of mesothelioma, confirms published findings on the magnitude of asbestos-related tumors in oil refineries.}, } @article {pmid10639767, year = {1999}, author = {Kumar, R and Gaur, SN}, title = {Malignant pleural mesothelioma without asbestos exposure.}, journal = {The Indian journal of chest diseases & allied sciences}, volume = {41}, number = {1}, pages = {61-64}, pmid = {10639767}, issn = {0377-9343}, mesh = {Humans ; Lung Neoplasms/complications/*diagnosis/pathology ; Male ; Mesothelioma/complications/*diagnosis/pathology ; Middle Aged ; Neoplasm Invasiveness ; Pleural Effusion/etiology ; Pleural Neoplasms/complications/*diagnosis/pathology ; }, abstract = {A 45-year-old male, non smoker and lecturer by profession was diagnosed as an advanced case of bilateral mesothelioma involving lung and pleura. He was never exposed to asbestos, which makes it a rare case.}, } @article {pmid10633953, year = {1999}, author = {Teschke, K and van Zwieten, L}, title = {Perceptions of the causes of bladder cancer, nasal cancer, and mesothelioma among cases and population controls.}, journal = {Applied occupational and environmental hygiene}, volume = {14}, number = {12}, pages = {819-826}, doi = {10.1080/104732299302053}, pmid = {10633953}, issn = {1047-322X}, mesh = {Aged ; Asbestos/adverse effects ; *Attitude to Health ; British Columbia ; Carcinogens/*adverse effects ; Case-Control Studies ; Data Collection/methods ; Female ; Humans ; Male ; Mesothelioma/*etiology ; Middle Aged ; Nose Neoplasms/*etiology ; Occupational Exposure/*adverse effects ; Population Surveillance ; Smoking/adverse effects ; Urinary Bladder Neoplasms/*etiology ; }, abstract = {To understand the reasons for underreporting of occupational cancers, we investigated cases' perceptions of the causes of cancer. As part of a case-control study in the province of British Columbia, Canada, 105 bladder cancer cases, 48 nasal cancer cases, 51 mesothelioma cases, and 159 population-based controls (frequency matched to cases on age and sex) were interviewed using structured questions about their smoking, medical, residential, occupational, and carcinogen exposure histories. We asked cases what they thought caused their disease, and asked population controls about their understanding of the etiologies of the three cancers. Most cases and controls (69%) indicated that they had "no idea" about causes, with the exception that the majority of mesothelioma cases (70%) recognized asbestos as a cause. Smoking was perceived as a cause of bladder cancer by 21 percent of cases. Many cases knew about the asbestos and smoking etiologies from discussions with their physicians. Chemicals were commonly cited as causes of nasal and bladder cancer, but very few specific known or probable carcinogens for these sites were named. Cases (12%) more frequently than controls (2%) thought prior disease or trauma was a cause for all three types of cancer. Other etiologic factors less frequently listed by subjects included environmental pollution, hereditary factors, drugs, and radiation. Most cases recognized the major cause of mesothelioma, but few subjects knew about lifestyle or occupational causes of bladder cancer or nasal cancer, suggesting that education about the multiple cancer risks of smoking and about occupational carcinogens needs to be improved.}, } @article {pmid10633330, year = {1999}, author = {al Jarad, N}, title = {Asbestos-related disease.}, journal = {Journal of the Royal College of Physicians of London}, volume = {33}, number = {6}, pages = {532-536}, pmid = {10633330}, issn = {0035-8819}, mesh = {Asbestosis/*diagnosis/pathology ; Humans ; Lung/diagnostic imaging ; Lung Neoplasms/etiology ; Mesothelioma/mortality ; Occupational Exposure ; Pleura/pathology ; Pleural Effusion/etiology ; Pleural Neoplasms/mortality ; Survival Rate ; Tomography, X-Ray Computed ; United Kingdom/epidemiology ; }, } @article {pmid10629562, year = {1999}, author = {Weyn, B and Van De Wouwer, G and Koprowski, M and Van Daele, A and Dhaene, K and Scheunders, P and Jacob, W and Van Marck, E}, title = {Value of morphometry, texture analysis, densitometry, and histometry in the differential diagnosis and prognosis of malignant mesothelioma.}, journal = {The Journal of pathology}, volume = {189}, number = {4}, pages = {581-589}, doi = {10.1002/(SICI)1096-9896(199912)189:4<581::AID-PATH464>3.0.CO;2-P}, pmid = {10629562}, issn = {0022-3417}, mesh = {Adenocarcinoma/pathology ; Cell Nucleus/pathology ; Chromatin/pathology ; Cytogenetic Analysis ; Diagnosis, Differential ; Epithelium/pathology ; Humans ; Hyperplasia ; Image Processing, Computer-Assisted ; Mesothelioma/*pathology ; Pleural Neoplasms/*pathology ; Prognosis ; }, abstract = {Malignant mesothelioma is a tumour with increasing incidence due to widespread use of its causative agent, asbestos, in the past decades. The poor survival necessitates a correct differentiation from other lesions at the same site, such as hyperplastic mesothelium and carcinomas metastatic to pleura or peritoneum. Since genetic and immunohistochemical markers are not absolutely differentiating, the diagnosis is based on the histology complemented with (immuno)histochemistry. However, as the tumour presents itself in numerous heterogeneous histological forms, visual evaluation is extremely difficult. In order to evaluate the prognostic and diagnostic performance of syntactic structure analysis (SSA), chromatin texture analysis, densitometry, and morphometry, an automated KNN-classification system has been used to compare Feulgen-stained tissue sections of hyperplastic mesothelium, malignant mesothelioma, and pulmonary adenocarcinoma. In addition, we also studied most discriminative aspects in the differentiation, typing, and prediction of survival. The results indicate that for the diagnosis of malignant mesothelioma, chromatin texture parameters outperform SSA, densitometry, and morphometry (recognition score=96.8 per cent). Most discriminative parameters highlight spatial patterns of the chromatin distribution that are hard to appraise visually and directly show the benefits of a quantitative approach. Typing of the tumour is best described by SSA parameters, relating to the spatial arrangement of the cells in the tissue (recognition score=94.9 per cent). In survival time classifications, chromatin texture yields the highest recognition score (82.9 per cent), although accurate estimations are unreliable due to a large degree of misclassification.}, } @article {pmid10628804, year = {1999}, author = {Ascoli, V and Scalzo, CC and Andreoni, M and Manente, L and Pistilli, A and Lo Coco, F}, title = {Kaposi's sarcoma following malignant mesothelioma.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {435}, number = {6}, pages = {612-615}, doi = {10.1007/s004280050448}, pmid = {10628804}, issn = {0945-6317}, mesh = {Antibodies, Viral/blood ; Antigens, Viral/immunology ; DNA Primers/chemistry ; DNA, Neoplasm/analysis ; DNA, Viral/genetics ; HIV Seronegativity ; Herpesvirus 8, Human/genetics/immunology/isolation & purification ; Humans ; Interleukin-6/analysis ; Male ; Mesothelioma/*complications/immunology/pathology ; Middle Aged ; Neoplasms, Second Primary/*etiology/immunology/pathology/virology ; Platelet-Derived Growth Factor/analysis ; Pleural Neoplasms/*complications/immunology/pathology ; Polymerase Chain Reaction ; Sarcoma, Kaposi/*etiology/immunology/pathology/virology ; Skin Neoplasms/*etiology/immunology/pathology/virology ; }, abstract = {We report the unusual occurrence of Kaposi's sarcoma following asbestos-related malignant mesothelioma, in a human deficiency virus (HIV)-negative Italian man. Seropositivity to human herpes virus 8 (HHV8) was documented at the time of mesothelioma diagnosis and preceded the onset of Kaposi' sarcoma with a time lapse of 13 months. HHV8 DNA was detected by polymerase chain reaction in lesional Kaposi's sarcoma but not within mesothelioma. By immunostaining, mesothelioma cells expressed interleukin-6 and platelet-derived growth factor, which are important for survival of Kaposi's sarcoma cells. Besides the possibility of a casual association, we hypothesize that mesothelioma-linked factors may have contributed to the development of Kaposi's sarcoma in the presence of HHV8 infection.}, } @article {pmid10618636, year = {1999}, author = {Carbone, M}, title = {Simian virus 40 and human tumors: It is time to study mechanisms.}, journal = {Journal of cellular biochemistry}, volume = {76}, number = {2}, pages = {189-193}, doi = {10.1002/(sici)1097-4644(20000201)76:2<189::aid-jcb3>3.0.co;2-j}, pmid = {10618636}, issn = {0730-2312}, support = {CA 77220-01/CA/NCI NIH HHS/United States ; }, mesh = {Asbestos/adverse effects ; Epithelium/virology ; Humans ; Mesothelioma/etiology/*virology ; Simian virus 40/genetics/*isolation & purification/pathogenicity ; Virulence ; }, abstract = {Several studies found simian virus 40 (SV40) in 47% to 83% of human mesotheliomas. Mesotheliomas are malignant tumors of the pleura and peritoneum, firmly associated with asbestos exposure. In this issue, Gazdar and colleagues ¿Shivapurkar et al., 1999 found that SV40 is present only in the malignant cells and not in the surrounding stromal cells. Using the microdissection technique, they found SV40 in 54% of 93 mesotheliomas of the epithelial type. The surrounding reactive stromal cells, (20 lung cancers and 14 mesotheliomas of the sarcomatoid/fibrous type) did not contain SV40, confirming the specificity of their positive findings. Furthermore, SV40 was found in 14% of 14 non-malignant reactive mesothelial cell proliferations. In 12 cases of mesothelioma a noninvasive (or in situ) component was also identified. In all four cases in which SV40 sequences were present in the invasive component, sequences were also present in the accompanying noninvasive component. These data suggest that the virus resides in the mesothelial cells prior to tumor development. The data address the remaining concerns raised at an International Meeting organized by the NIH, FDA, and CDC in 1997 to definitively associate SV40 with human mesothelioma. It is time now to investigate the pathogenic mechanisms of this association, and if SV40-infected mesothelial cells are more susceptible to other carcinogens, such as asbestos. Furthermore, we must investigate the interaction between the host immune system and SV40-infected mesothelial cells, and study if the immunosuppressive activity of asbestos interferes with tumor rejection. These studies should lead to a better understanding of mesothelioma pathogenesis, and possibly to new therapeutic approaches aimed at interfering with the expression of the SV40 genome and/or at eliciting a strong immune response against SV40 infected mesothelial cells.}, } @article {pmid10618635, year = {1999}, author = {Shivapurkar, N and Wiethege, T and Wistuba, II and Salomon, E and Milchgrub, S and Muller, KM and Churg, A and Pass, H and Gazdar, AF}, title = {Presence of simian virus 40 sequences in malignant mesotheliomas and mesothelial cell proliferations.}, journal = {Journal of cellular biochemistry}, volume = {76}, number = {2}, pages = {181-188}, doi = {10.1002/(sici)1097-4644(20000201)76:2<181::aid-jcb2>3.3.co;2-0}, pmid = {10618635}, issn = {0730-2312}, support = {P50-CA70907/CA/NCI NIH HHS/United States ; }, mesh = {Antigens, Polyomavirus Transforming/genetics ; Asbestos/adverse effects ; Cell Division ; Epithelium/pathology/virology ; Humans ; Lung Neoplasms/pathology/virology ; Mesothelioma/pathology/*virology ; Peritoneal Neoplasms/pathology/virology ; Pleural Neoplasms/pathology/virology ; Simian virus 40/genetics/*isolation & purification ; }, abstract = {Malignant mesotheliomas (MMs) are pleural-, pericardial-, or peritoneal-based neoplasms usually associated with asbestos exposure. Mesothelial cells are biphasic and may give rise to epithelial and sarcomatous MMs. In addition, benign or atypical proliferations of mesothelial cells may occur in response to many stimuli. There have been recent reports of simian virus 40 (SV40) DNA large T antigen (Tag) sequences in pleural MMs. To further understand the relationship between SV40, MMs, and mesothelial proliferations, we studied 118 MMs from multiple sites in Germany and North America, including 93 epithelial pleural, 14 sarcomatous or mixed pleural MMs, and 11 peritoneal MMs. In 12 pleural MMs, adjacent noninvasive tumor foci were identified and studied separately. Information about asbestos exposure (detailed history and/or microscopic examination for asbestos bodies) was available from 43 German patients. In addition, 13 examples of reactive mesothelium and 20 lung cancers from the United States were tested. DNA was extracted from frozen tumor and adjacent nontumorous tissues or after microdissection of archival formalin-fixed, paraffin-embedded microslides. Two rounds of PCR were performed with primers SVFor 3 and SVRev, which amplify a 105 bp region specific for SV40 Tag. The specificity of the PCR product was confirmed in some cases by sequencing. Our major findings were: 1) Specific SV40 viral sequences were present in 57% of epithelial invasive MMs, of both pleural and peritoneal origin. No significant geographic differences were found, and frozen and paraffin-embedded tissues were equally suitable for analysis. 2) There was no apparent relationship between the presence of SV40 sequences and asbestos exposure. 3) SV40 sequences were present in the surface (noninvasive) components of epithelial MMs. 4) SV40 sequences were not detected in MMs of sarcomatous or mixed histologies. 5) Viral sequences were present in two of 13 samples (15%) of reactive mesothelium. 6) Lung cancers lacked SV40 sequences, as did non-malignant tissues adjacent to MMs. Our findings demonstrate the presence of SV40 sequences in epithelial MMs of pleural and peritoneal origin and their absence in tumors with a sarcomatous component. Viral sequences may be present in reactive and malignant mesothelial cells, but they are absent in adjacent tissues and lung cancers.}, } @article {pmid10615096, year = {2000}, author = {Agudo, A and González, CA and Bleda, MJ and Ramírez, J and Hernández, S and López, F and Calleja, A and Panadès, R and Turuguet, D and Escolar, A and Beltrán, M and González-Moya, JE}, title = {Occupation and risk of malignant pleural mesothelioma: A case-control study in Spain.}, journal = {American journal of industrial medicine}, volume = {37}, number = {2}, pages = {159-168}, doi = {10.1002/(sici)1097-0274(200002)37:2<159::aid-ajim1>3.0.co;2-0}, pmid = {10615096}, issn = {0271-3586}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Case-Control Studies ; Female ; Humans ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Occupational Diseases/*epidemiology ; Occupational Exposure ; Pleural Neoplasms/*epidemiology ; Spain/epidemiology ; }, abstract = {BACKGROUND: The association of mesothelioma and asbestos exposure is well known, but some data suggest that probably many people are still being exposed to asbestos without knowing it.

METHODS: Between 1993 and 1996, 132 cases (77% males) of histologically confirmed malignant pleural mesothelioma and 257 controls, residents in two provinces of Spain (Barcelona and C¿adiz), were interviewed. They were classified according to their probability and intensity of occupational asbestos exposure by a panel of industrial hygienists, based on a detailed occupational history.

RESULTS: Age and sex-adjusted odds ratio (OR) for the highest probability of exposure to asbestos was 13.2 (95% confidence interval 6.4-27.3), and 27.1 (9. 28-79.3) for high intensity. A dose-response trend was observed for both, probability and intensity. Overall, 61% of cases and 42% of controls had ever worked in an occupation with risk of asbestos exposure, with an OR of 2.59 (1.60-4.22). In our population 62% of cases could be attributed to occupational asbestos exposure.

CONCLUSIONS: A high risk of pleural mesothelioma due to occupational asbestos exposure is confirmed, but there is still a sizeable proportion for which no evidence of occupational exposure was found. Most of these cases could be due to other sources of asbestos exposure, mainly domestic or environmental.}, } @article {pmid10596542, year = {1999}, author = {Placidi, D and Porru, S and Alessio, L}, title = {[A report of 3 cases of pleural mesothelioma with unusual asbestos exposure].}, journal = {La Medicina del lavoro}, volume = {90}, number = {5}, pages = {671-680}, pmid = {10596542}, issn = {0025-7818}, mesh = {Aged ; Asbestos/*adverse effects ; Biopsy ; Environmental Exposure/*adverse effects ; Female ; Humans ; Male ; Mesothelioma/diagnosis/*etiology ; Middle Aged ; Occupational Diseases/diagnosis/*etiology ; Pleura/pathology ; Pleural Neoplasms/diagnosis/*etiology ; }, abstract = {The occurrence of malignant pleural mesothelioma (MT) is a sentinel event in occupational and environmental medicine. The association of pleural MT and asbestos exposure is well documented and it is well known that no threshold can be demonstrated below which there is no risk of developing MT. During the period 1994-1998, 3 patients were referred from the Pneumology Division to the Occupational Medicine Department of the Spedali Civili in Brescia. They had MT and they had a peculiar asbestos exposure. A thorough occupational and environmental history was taken by means of a standardized questionnaire. The first patient was environmentally exposed to crocidolite when she lived near an asbestos mine in Australia. The second was a teacher and the third was a goldsmith and both were occupationally exposed to asbestos. The case descriptions revealed the importance of a standardized evaluation of occupational and environmental exposure to asbestos. In this way otherwise ignored asbestos exposures can be identified therefore avoiding an underestimation of MT attributable to asbestos. The role of the occupational physician, both in hospital referrals and while taking standardized histories, is also stressed along with the importance of this contribution on the one hand to the epidemiological recording of sentinel events and on the other to the etiological definition of the cases, which was in fact our principal aim.}, } @article {pmid10590773, year = {1999}, author = {Schermer, TR and Cox, AL}, title = {[Diagnosis of malignant pleural mesothelioma and asbestosis].}, journal = {Nederlands tijdschrift voor geneeskunde}, volume = {143}, number = {47}, pages = {2354-2360}, pmid = {10590773}, issn = {0028-2162}, mesh = {Asbestosis/complications/*diagnosis/economics/epidemiology ; Eligibility Determination/*standards ; Global Health ; Humans ; Mesothelioma/complications/*diagnosis/economics/epidemiology ; Netherlands/epidemiology ; Pleural Neoplasms/*diagnosis/economics/epidemiology/etiology ; Workers' Compensation/economics/*standards ; }, abstract = {The incidence of malignant mesothelioma, the main consequence of exposure to asbestos, will increase considerably in the Netherlands in the coming decades. In the next 35 year, some 20,000 people will die from malignant mesothelioma. The diagnosis of malignant pleural mesothelioma in practice is based on histological examination in about 80%, on cytological examination in 15% and on other forms of examination, e.g., high resolution computer tomography (HRCT), in 6% of the cases. Using a combination of various noninvasive methods, such as anamnesis, physical and röntgenologic examination, HRCT and spirometry, the diagnosis of asbestosis is made erroneously in 5% of the patients examined. With regard to allowance of financial compensation to patients with pleural mesothelioma and asbestosis, a part is played by the fact that views differ internationally concerning the criteria on which the diagnosis should be based. For mesothelioma cytologic and histologic examination are the most important. For asbestosis, the Health Council considers HRCT as crucial, if necessary supplemented by histological examination, plus a history of exposure to asbestos and pulmonary dysfunction. In mesothelioma cytological and histological examination are the most important.}, } @article {pmid10590549, year = {1999}, author = {Yeung, P and Rogers, A and Johnson, A}, title = {Distribution of mesothelioma cases in different occupational groups and industries in Australia, 1979-1995.}, journal = {Applied occupational and environmental hygiene}, volume = {14}, number = {11}, pages = {759-767}, doi = {10.1080/104732299302189}, pmid = {10590549}, issn = {1047-322X}, mesh = {Aged ; Asbestos/*adverse effects ; Australia/epidemiology ; Female ; Humans ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Diseases/*epidemiology/etiology ; Occupations/*statistics & numerical data ; Population Surveillance/methods ; }, abstract = {Australia was a producer and user of asbestos and has one of the highest national incidences of mesothelioma in the world. The incidence is still rising and expected to do so for another 10-20 years. A study was conducted in 1996 to examine the past and current incidence rates of mesothelioma in a number of industries and occupations as the basis for predicting future outcomes. Occupational histories of a total of 3758 mesothelioma cases collected by two sequential national schemes--the Australian Mesothelioma Surveillance Program (1979-1985) and Australian Mesothelioma Register (1986-1995)--were reviewed and coded by the authors. The building industry contributed the largest number of cases nationwide followed by shipbuilding and repair, asbestos cement production, crocidolite mining and milling, railway locomotive construction and repair, coal-fired power stations, and other engineering operations. The mean latency between initial occupational asbestos exposure and diagnosis of the disease was 37.4 years (range = 4-66 years) for cases notified between 1979 and 1985, and 41.4 years (range = 6-84 years) for those between 1986 and 1995. Trends for each industry group have been changing considerably in the past 16 years, with the traditional primary asbestos industry cases from crocidolite mining and milling now on the decline and cases from asbestos cement production having plateaued. In contrast, more recently, more cases were observed from the asbestos user industries such as the building industry, and from occupations such as plumbers, carpenters, machinists, and car mechanics. These increases might be a reflection of the longer latency effects of the intermittent and less severe exposures in these larger occupational groups.}, } @article {pmid10587993, year = {1999}, author = {Goldberg, M and Goldberg, S and Luce, D}, title = {[Regional differences in the compensation of pleural mesothelioma as occupational disease in France (1986-1993)].}, journal = {Revue d'epidemiologie et de sante publique}, volume = {47}, number = {5}, pages = {421-431}, pmid = {10587993}, issn = {0398-7620}, mesh = {Female ; France/epidemiology ; Humans ; Male ; Mesothelioma/*epidemiology ; Occupational Diseases/*epidemiology ; Pleural Neoplasms/*epidemiology ; Probability ; *Workers' Compensation ; }, abstract = {BACKGROUND: Occupational exposure to asbestos is responsible for 80% at least of all mesothelioma in developed countries. In France there are important regional differences in the rate of mesothelioma compensated as occupational diseases, without knowing if these differences could be explained by a real difference of risk. The objective here is to quantify these regional differences in relation with the differences of level of risk.

METHODS: The analysis compares, for each of the 16 regions of the national social security system, mortality for both genders and among men by pleural cancer (ICD 163) in the general population and mesothelioma compensated as occupational diseases during the 1986-1993 period. We computed for each region the number of expected compensated mesothelioma under the hypothesis where the regional distributions of compensated mesothelioma and mesothelioma deaths are the same; as well as the percentage of compensated mesothelioma compared to the deaths, and the variation from the national mean under two hypotheses, high and low; and the probability that a mesothelioma is compensated as an occupational disease taking as a reference the "best" region.

RESULTS: The compensation rate differed significantly among regions (p < 0.05) and for men, the rate between observed and expected numbers of compensated mesothelioma varied from 0.15 (region of Montpellier) to 2.29 (region of Nantes), a ratio over 15. For all of France, the compensation rate was 25% under the best hypothesis. The region of Nantes compensated 61.5% of the male mesothelioma as occupational diseases, while the region of Montpellier and Clermont-Ferrand only around 5%. The probability for a mesothelioma to be compensated, compared to the region of Nantes, was 2.5 times less in national average, and about 10 times less in Montpellier and Clermont-Ferrand regions.

CONCLUSION: In spite of limits linked to the imprecision of the available data, important regional differences in term of compensation of mesothelioma as occupational diseases clearly exist. Indications lead to think that their origin lies essentially in differences between physicians when considering the occupational etiology of mesothelioma, but differences within the system of compensation of occupational diseases can not be excluded. An improvement of the national statistical system concerning occupational diseases is highly recommendable.}, } @article {pmid10586447, year = {1999}, author = {Dourthe, LM and Coulon, MA and Piperno Neumann, S and Morere, JF and Breau, JL}, title = {[Peritoneal mesothelioma, a new complication of pica syndrome: apropos of a case].}, journal = {La Revue de medecine interne}, volume = {20}, number = {11}, pages = {1047-1048}, doi = {10.1016/s0248-8663(00)87089-7}, pmid = {10586447}, issn = {0248-8663}, mesh = {Adenocarcinoma/pathology ; Asbestos/adverse effects ; Female ; Humans ; Mesothelioma/*etiology/pathology ; Middle Aged ; Neoplasms, Multiple Primary/pathology ; Ovarian Neoplasms/pathology ; Peritoneal Neoplasms/*etiology/pathology ; Pica/*complications ; }, } @article {pmid10585573, year = {1999}, author = {Gross-Goupil, M and Ruffié, P}, title = {[Malignant pleural mesothelioma].}, journal = {Bulletin du cancer}, volume = {Suppl 3}, number = {}, pages = {43-54}, pmid = {10585573}, issn = {0007-4551}, mesh = {Humans ; *Mesothelioma/diagnosis/epidemiology/therapy ; Neoplasm Staging ; *Pleural Neoplasms/diagnosis/epidemiology/therapy ; Prognosis ; Risk Factors ; }, abstract = {The malignant pleural mesothelioma is a rare tumor of the general population. The exposure of asbestos still remains the main factor of risk, found in 72 to 95 % of the patients. The diagnosis is difficult. The symptoms are poor, with most often chronic pleural effusion, with dyspnea, associated with localized chest pain. The histological diagnosis is made on thoracoscopic biopsy. Analysis of the histochemical profile (PAS-D, hyaluronidase, vimentine), the use of immunochemistry (CEA, keratines), and electron microscopy can facilitate the making of the diagnosis. There is 3 different entities of malignant mesothelioma: the epithelial type, mixed, and sarcomatous. The tagging is based on thoracic scanner, to determinate the extent of the tumor, her relation with the local structures, and the possible involvement of the mediastinal lymph nodes. There is several staging systems, the Butchart's staging classification, and most recently the IMIG (International Mesothelioma Interest Group) classification. The significant prognostic factors, in multivariate analysis are: the stage of the disease, the histologic type, and the performance status of the patient. The current therapeutic maneuvers (surgery, chemotherapy, radiotherapy) did not show significant improvement of the survival. The radical surgery, like pleuropneumonectomy, should be consider only for patients with an early stage of the disease. The chemotherapy, with single agent or in combination, still remains disappointing, with objective response rates between 20 and 30 %, in best cases. The curative radiotherapy is limited by the importance of the target-volume, and the proximity of critical organ (lung, heart). Only the preventive radiotherapy, on scars, niddle or surgical tracts is recommended. Immunotherapy, by systemic or intracavitary administration, remains limited because of the toxicity, especially infection. All of the therapeutic maneuvers should be proposed in clinical trials.}, } @article {pmid10554340, year = {1999}, author = {Kanazawa, S and Nagae, T and Fujiwara, T and Fujiki, R and Mukai, N and Sugihara, Y and Yamaguchi, N and Ohtani, H and Higami, Y and Ikeda, T and Tsunoda, T}, title = {Malignant mesothelioma of the tunica vaginalis testis: report of a case.}, journal = {Surgery today}, volume = {29}, number = {10}, pages = {1106-1110}, pmid = {10554340}, issn = {0941-1291}, mesh = {Aged ; Asbestos/adverse effects ; Humans ; Male ; Mesothelioma/epidemiology/*pathology/surgery ; Testicular Neoplasms/epidemiology/*pathology/surgery ; Testis/pathology ; }, abstract = {We describe herein the case of a 68-year-old man with malignant mesothelioma of the tunica vaginalis testis. The pathological diagnosis was based upon the clinical findings, gross and microscopic morphology, and special stains. Malignant mesothelioma is a rare tumor associated with asbestos exposure that can be effectively treated with orchidectomy via an inguinal approach.}, } @article {pmid10582149, year = {1999}, author = {Toma, S and Raffo, P and Isnardi, L and Palumbo, R}, title = {Retinoids in lung cancer chemoprevention and treatment.}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {10 Suppl 5}, number = {}, pages = {S95-102}, doi = {10.1093/annonc/10.suppl_5.s95}, pmid = {10582149}, issn = {0923-7534}, mesh = {*Cell Transformation, Neoplastic ; Chemoprevention ; Combined Modality Therapy ; Humans ; Lung Neoplasms/drug therapy/*prevention & control ; Prognosis ; Retinoids/pharmacology/*therapeutic use ; }, abstract = {In this review, we aim to synthesize the emerging picture of retinoids in lung cancer through a summary of ongoing investigations in biology, chemoprevention and therapy settings, in an attempt to clarify the possible role of these agents in such a disease. Early work in head and neck cancer has evidenced the capability of retinoids to interrupt field carcinogenesis by reversing premalignant lesions and decreasing the incidence of second primary tumors (SPTs). At this time, the completed randomized trials in lung cancer have failed to demonstrate an evident chemopreventive effect of the tested agents on different study end points, although both a marginally significant benefit of retinol palmitate in time-to-development rates for smoke-related SPTs and a potential preventive effect of retinol supplementation against mesothelioma in selected populations of asbestos-exposed workers have been recently reported. Concerning the role of retinoids in lung cancer treatment, a moderate activity of 13-cis-retinoic acid (13cRA) or all-transretinoic acid (ATRA) as single agents has been reported in small series of advanced, mostly pretreated lung cancer patients. More encouraging findings derive from combination studies, in which retinoids, especially ATRA, are added to either alpha-interferon or chemotherapy and radiotherapy. Major recent advances have been made towards the understanding of retinoids mechanisms of action; at this regard, the role of RAR-beta basal or treatment-induced levels seems to be of particular interest as intermediate end point and/or independent prognostic factor, besides their known importance in lung carcinogenesis. Future research for chemopreventive and therapeutic programs with retinoids in lung cancer should be focused on the investigation of new generation compounds with a specificity for individual retinoid nuclear receptors. Such selective molecules may have a greater activity against lung cancer, with a more favourable toxicity profile, as recently suggested by our preliminary data on Ro 41-5253.}, } @article {pmid10582032, year = {1999}, author = {Howie, RM}, title = {Minimising health hazards associated with derogated products and in-situ materials containing chrysotile contaminated with amphibole asbestos fibres.}, journal = {The Annals of occupational hygiene}, volume = {43}, number = {7}, pages = {493-498}, doi = {10.1016/s0003-4878(99)00079-4}, pmid = {10582032}, issn = {0003-4878}, mesh = {Asbestos, Amphibole/*adverse effects ; Asbestos, Serpentine/*adverse effects/*chemistry ; Humans ; International Cooperation ; Lung Neoplasms/etiology ; Manufactured Materials ; Mesothelioma/etiology ; *Public Health ; *Public Policy ; }, } @article {pmid10582027, year = {1999}, author = {McDonald, JC and McDonald, AD and Hughes, JM}, title = {Chrysotile, tremolite and fibrogenicity.}, journal = {The Annals of occupational hygiene}, volume = {43}, number = {7}, pages = {439-442}, pmid = {10582027}, issn = {0003-4878}, mesh = {Aged ; Asbestos, Amphibole/*adverse effects ; Asbestos, Serpentine/*adverse effects ; Cohort Studies ; Humans ; Lung/pathology ; Lung Neoplasms/*etiology ; Male ; Mesothelioma/*etiology ; Middle Aged ; *Mining ; Occupational Exposure ; *Occupational Health ; Odds Ratio ; Radiography, Thoracic ; Risk Assessment ; }, abstract = {Recently published analyses have shown that the risks of mesothelioma and lung cancer in Quebec chrysotile miners and millers were related to estimated level of fibrous tremolite in the mines where they had worked. An analysis has therefore been made of radiographic changes in men who in 1965 were employed by companies in Thetford Mines where the same question could be examined for fibrogenicity. Of 294 men who met the necessary requirements, 129 had worked in six centrally located mines, where the tremolite content was thought to be high, 81 in 10 peripheral mines where it was thought to be low and 84 in both. The median prevalence of small parenchymal opacities (> or = 1/0) in chest radiographs read by six readers was higher among men ever than never employed in the central mines (13.6% against 7.4%), despite the fact that the mean cumulative exposure was lower in the former (430 mpcf.y vs 520 mpcf.y). After accounting by logistic regression for cigarette smoking, age, smoking-age interaction and cumulative exposure, the adjusted odds ratio for central mine employment was 2.44 (95% lower bound: 1.06). Together with other surveys of asbestos miners and millers, this study suggests that amphibole fibres, including tremolite, are more fibrogenic than chrysotile, perhaps to the same extent that they are carcinogenic, though the data available were not sufficient to address the latter question.}, } @article {pmid10554177, year = {1999}, author = {Weyn, B and van de Wouwer, G and Kumar-Singh, S and van Daele, A and Scheunders, P and van Marck, E and Jacob, W}, title = {Computer-assisted differential diagnosis of malignant mesothelioma based on syntactic structure analysis.}, journal = {Cytometry}, volume = {35}, number = {1}, pages = {23-29}, doi = {10.1002/(sici)1097-0320(19990101)35:1<23::aid-cyto4>3.0.co;2-p}, pmid = {10554177}, issn = {0196-4763}, mesh = {Adenocarcinoma/classification/*pathology ; Analysis of Variance ; Diagnosis, Computer-Assisted/*methods ; Diagnosis, Differential ; Epithelium/pathology ; Fractals ; Humans ; Hyperplasia/classification/pathology ; Image Processing, Computer-Assisted ; Lung Neoplasms/classification/*pathology ; Mesothelioma/classification/*pathology ; Multivariate Analysis ; }, abstract = {BACKGROUND: Malignant mesothelioma, a mesoderm-derived tumor, is related to asbestos exposure and remains a diagnostic challenge because none of the genetic or immunohistochemical markers have yet been proven to be specific. To assist in the identification of mesothelioma and to differentiate it from other common lesions at the same location, we have tested the performance of syntactic structure analysis (SSA) in an automated classification procedure.

MATERIALS AND METHODS: Light-microscopic images of tissue sections of malignant mesothelioma, hyperplastic mesothelium, and adenocarcinoma were analyzed using parameters selected from the Voronoi diagram, Gabriel's graph, and the minimum spanning tree which were classified with a K-nearest-neighbor algorithm.

RESULTS: Results showed that mesotheliomas were diagnosed correctly in 74% of the cases; 76% of the adenocarcinomas were correctly graded, and 88% of the mesotheliomas were correctly typed. The performance of the parameters was dependent on the obtained classification (i.e., tumor-tumor versus tumor-benign).

CONCLUSIONS: Our results suggest that SSA is valuable in the differential classification of mesothelioma and that it supplements a visually appraised diagnosis. The recognition scores may be increased by a combination of SSA with, for example, cellular or nuclear parameters, measured at higher magnifications to form a solid base for fully automated expert systems.}, } @article {pmid10561683, year = {1999}, author = {Robinson, CF and Petersen, M and Palu, S}, title = {Mortality patterns among electrical workers employed in the U.S. construction industry, 1982-1987.}, journal = {American journal of industrial medicine}, volume = {36}, number = {6}, pages = {630-637}, doi = {10.1002/(sici)1097-0274(199912)36:6<630::aid-ajim5>3.0.co;2-6}, pmid = {10561683}, issn = {0271-3586}, mesh = {Adult ; Cause of Death ; Construction Materials ; Electricity ; Female ; Humans ; Labor Unions ; Male ; Middle Aged ; *Mortality ; Neoplasms/mortality ; Occupational Health/*statistics & numerical data ; United States/epidemiology ; }, abstract = {BACKGROUND: Studies of electrical workers in the utility and manufacturing industries have reported excess site-specific cancer. No previous studies of electrical workers in the construction industry have been conducted.

METHODS: Our study evaluated the mortality patterns of 31,068 U.S. members of the International Brotherhood of Electrical Workers who primarily worked in the construction industry and died 1982-1987.

RESULTS: Comparison to the U.S. population by using the NIOSH life table showed significantly elevated proportionate mortality for many causes. Excess mortality for leukemia (proportionate mortality ratio (PMR)=115) and brain tumors (PMR=136) is similar to reports of electrical workers with occupational exposure to electric and magnetic fields in the electric utility or manufacturing industry. Excess deaths due to melanoma skin cancer (PMR=123) are consistent with findings of other PCB-exposed workers. A significantly elevated PMR was observed for the diseases caused by asbestos: lung cancer (PMR=117), asbestosis (PMR=247), and malignant mesothelioma (PMR=356) and from fatal injuries, particularly electrocutions (PMR=1180). The findings of statistically significant excess deaths for prostate cancer (PMR=107), musculoskeletal disease (PMR=130), suicide (PMR=113), and disorders of the blood-forming organs (PMR=141) were unexpected.

CONCLUSIONS: Results suggest that more detailed investigations of occupational risk factors and evaluation of preventive practices are needed to prevent excess mortality in this hazardous occupation. Am. J. Ind. Med. 36:630-637, 1999. Published 1999 Wiley-Liss, Inc.}, } @article {pmid10546514, year = {1999}, author = {Wallnöfer-de Jong, A}, title = {[Diagnosis and therapy of asbestos exposure].}, journal = {Praxis}, volume = {88}, number = {41}, pages = {1677-1679}, pmid = {10546514}, issn = {1661-8157}, mesh = {Aged ; Asbestosis/*diagnosis/therapy ; Diagnosis, Differential ; Humans ; Male ; Mesothelioma/*diagnosis/therapy ; Pleural Neoplasms/*diagnosis/therapy ; Precancerous Conditions/*diagnosis/therapy ; Tomography, X-Ray Computed ; }, } @article {pmid10543297, year = {1999}, author = {Kinnula, VL}, title = {Oxidant and antioxidant mechanisms of lung disease caused by asbestos fibres.}, journal = {The European respiratory journal}, volume = {14}, number = {3}, pages = {706-716}, doi = {10.1034/j.1399-3003.1999.14c35.x}, pmid = {10543297}, issn = {0903-1936}, mesh = {Animals ; Antioxidants/*metabolism/therapeutic use ; Apoptosis/genetics ; Asbestos/*adverse effects ; Asbestosis/*etiology/metabolism/pathology/prevention & control ; Cell Division/drug effects/genetics ; DNA Damage/drug effects ; Humans ; Nitrogen Oxides/metabolism ; *Oxidation-Reduction/drug effects ; Reactive Oxygen Species/metabolism ; }, abstract = {The pathogenesis of asbestos-related lung diseases is complicated and still poorly understood. Studies on animal models and cell cultures have indicated that asbestos fibres generate reactive oxygen and nitrogen species and cause oxidation and/or nitrosylation of proteins and deoxyribonucleic acid as a marker of cell injury. These effects are potentiated by the inflammation caused by the fibres. Recent studies have shown that individual variability in the antioxidant and/or detoxifying mechanisms probably has an important role in the development of asbestos-related lung diseases. Asbestos fibres cause both cell proliferation and apoptosis by multiple mechanisms, one of them being activation of signal transduction pathways by reactive oxygen and nitrogen species. Asbestos activates transcription factors such as nuclear factor kappa B, which has been shown to lead to the upregulation of antioxidant enzymes, most importantly manganese superoxide dismutase. This enzyme is also overexpressed in asbestos-related human malignant mesothelioma, whereas the induction of other antioxidant enzymes (copper-zinc superoxide dismutase, catalase, glutathione peroxidase) by asbestos fibres appears to be marginal. The significance of antioxidant enzymes in asbestos related diseases has, however, remained unclear. Furthermore, previous studies have not been able to offer successful therapies to the patients with asbestos-associated diseases. Only an improved understanding of the pathogenetic mechanisms in the human lung provides a basis for future therapies for asbestos-related diseases.}, } @article {pmid10536123, year = {1999}, author = {Perkins, RC and Broaddus, VC and Shetty, S and Hamilton, S and Idell, S}, title = {Asbestos upregulates expression of the urokinase-type plasminogen activator receptor on mesothelial cells.}, journal = {American journal of respiratory cell and molecular biology}, volume = {21}, number = {5}, pages = {637-646}, doi = {10.1165/ajrcmb.21.5.3225}, pmid = {10536123}, issn = {1044-1549}, mesh = {Animals ; Asbestos, Crocidolite/*pharmacology ; Asbestos, Serpentine/*pharmacology ; Calcium Compounds/pharmacology ; Cell Membrane/metabolism ; Cells, Cultured ; Culture Media, Conditioned/pharmacology ; Epithelial Cells/*drug effects/metabolism ; Female ; Humans ; Immunohistochemistry ; Iodine Radioisotopes ; Monocytes/drug effects ; Plasminogen Activators/biosynthesis ; Pleura/cytology ; RNA, Messenger/biosynthesis ; Rabbits ; Receptors, Cell Surface/*biosynthesis/genetics ; Receptors, Urokinase Plasminogen Activator ; Silicates/pharmacology ; Specific Pathogen-Free Organisms ; Up-Regulation/drug effects ; Urokinase-Type Plasminogen Activator/metabolism ; }, abstract = {Inhalation of asbestos is associated with pathologic changes in the pleural space, including pleural thickening, pleural plaques, and mesothelioma. These processes are characterized by altered local proteolysis, cellular proliferation, and cell migration, suggesting that the urokinase-type plasminogen activator receptor (uPAR) could be involved in the pathogenesis of asbestos-induced pleural disease. We hypothesized that mesothelial cell uPAR expression is induced by exposure to asbestos. To test this hypothesis, we used complementary techniques in rabbit and human mesothelial cells to determine whether uPAR expression is altered by exposure to asbestos. uPAR expression was induced by chrysotile and crocidolite asbestos, but not by wollastonite, as indicated by binding of radiolabeled urokinase-type plasminogen activator (uPA) to rabbit or human mesothelial cells. uPA was not induced by fiber exposure. Exposure to exogenous uPA increased uPA activity of cells exposed to wollastonite but not asbestos-treated MeT5A cells. uPAR expression increased further when asbestos was preincubated with vitronectin (VN) or serum. Increases in uPAR expression were confirmed by binding of uPA to uPAR in cell membrane preparations and immunofluorescent staining of uPAR at the cell surface, and were associated with increases in steady-state uPAR messenger RNA. Mesothelial cell uPAR expression was also induced by media from monocytes cultured with asbestos incubated with VN and serum. By antibody neutralization, the latter effect appeared to be in part mediated by transforming growth factor-beta. We found that asbestos increases uPAR at the surface of rabbit and human mesothelial cells, suggesting that altered expression of this receptor could be involved in asbestos-induced remodeling of the pleural mesothelium.}, } @article {pmid10530617, year = {1999}, author = {Goodman, M and Morgan, RW and Ray, R and Malloy, CD and Zhao, K}, title = {Cancer in asbestos-exposed occupational cohorts: a meta-analysis.}, journal = {Cancer causes & control : CCC}, volume = {10}, number = {5}, pages = {453-465}, doi = {10.1023/a:1008980927434}, pmid = {10530617}, issn = {0957-5243}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Carcinogens/*adverse effects ; Cohort Studies ; Dose-Response Relationship, Drug ; Female ; Humans ; Incidence ; Laryngeal Neoplasms/epidemiology/etiology ; Lung Neoplasms/epidemiology/*etiology ; Male ; Middle Aged ; Neoplasms/epidemiology/*etiology ; Occupational Diseases/*epidemiology ; Occupational Exposure ; *Occupational Health ; }, abstract = {OBJECTIVE: To examine existing asbestos-exposed occupational cohorts and apply a meta-analytic technique to determine the magnitude of association between exposure and lung cancer and to investigate other cancer sites that may be related to such an exposure.

METHODS: We summarized the data from 69 asbestos-exposed occupational cohorts reporting on cancer morbidity and mortality. Data were extracted regarding numbers of deaths for each cancer, numbers of mesotheliomas, occupations and latency for respiratory, gastrointestinal, urinary and lymphohematopoietic cancers. For each cancer, we calculated a meta-SMR and examined heterogeneity of results using a chi-square test and by calculating a Z-statistic for each study. To examine the dose-response effect, we divided the studies into tertiles according to the percentage of mesothelioma deaths that served as a proxy estimation of asbestos exposure.

RESULTS: Lung cancer data demonstrated meta-SMRs of 163 and 148 with and without latency, respectively, with significant heterogeneity of results even after stratification according to occupational groups. Stratification of lung cancer studies according to percentage of mesothelioma deaths showed a dose-response effect. Z-scores ranged from -12.21 to + 29.49. Analysis for laryngeal cancer yielded meta-SMRs of 157 and 133 with and without latency, respectively, demonstrating homogeneous results across studies but accompanied by no evidence of a dose-response effect. Data for gastrointestinal cancers showed no evidence of a significant association and no dose-response effect. Kidney cancer demonstrated statistically non-significant meta-SMRs of 120 (95% CI 88-160) and 111 (95% CI 94-131) with and without latency respectively.

CONCLUSIONS: This meta-analysis demonstrates a wide variability of the association between occupational asbestos and lung cancer. There was a suggestion of an association between asbestos and laryngeal carcinoma and no clear association with other cancers.}, } @article {pmid10529938, year = {1999}, author = {Ramazzini, C}, title = {Call for an international ban on asbestos.}, journal = {Journal of occupational and environmental medicine}, volume = {41}, number = {10}, pages = {830-832}, doi = {10.1097/00043764-199910000-00003}, pmid = {10529938}, issn = {1076-2752}, mesh = {Asbestos/*adverse effects ; Asbestosis/prevention & control ; Environmental Exposure/*prevention & control ; *Global Health ; Humans ; Mesothelioma/prevention & control ; Pleural Neoplasms/prevention & control ; Societies, Medical ; }, abstract = {To eliminate the burden of disease and death that is caused worldwide by exposure to asbestos, the Collegium Ramazzini calls for an immediate ban on all mining and use of asbestos. To be effective, the ban must be international in scope and must be enforced in every country in the world.}, } @article {pmid10522541, year = {1999}, author = {Stamat, JC and Chekan, EG and Ali, A and Ko, A and Sporn, TA and Eubanks, WS}, title = {Laparoscopy and mesothelioma.}, journal = {Journal of laparoendoscopic & advanced surgical techniques. Part A}, volume = {9}, number = {5}, pages = {433-437}, doi = {10.1089/lap.1999.9.433}, pmid = {10522541}, issn = {1092-6429}, mesh = {Aged ; Humans ; *Laparoscopy ; Male ; Mesothelioma/*diagnosis/pathology ; Peritoneal Neoplasms/*diagnosis/pathology ; }, abstract = {Malignant mesothelioma is a well-recognized long-term sequela of chronic asbestos exposure. Asbestos use in the United States began in the 1950s and was widespread until the mid-1970s. Although currently only 2.2 cases per million population per year are diagnosed, disease incidence is increasing because of the long latency of this neoplasm. A latency of 15-50 years means that a higher incidence of this neoplasm can be anticipated in the future. The authors report a patient with peritoneal mesothelioma and no known prior exposure to asbestos. The diagnosis was confirmed by exploratory laparoscopy, which entailed biopsies of the diaphragm and of the peritoneal and abdominal walls, and by cytologic evaluation of 700 ml ascitis fluid. At present, exploratory laparoscopy offers the quickest, safest, and least invasive way to confirm the clinical diagnosis of peritoneal malignant mesothelioma.}, } @article {pmid10506753, year = {1999}, author = {Hirvonen, A and Mattson, K and Karjalainen, A and Ollikainen, T and Tammilehto, L and Hovi, T and Vainio, H and Pass, HI and Di Resta, I and Carbone, M and Linnainmaa, K}, title = {Simian virus 40 (SV40)-like DNA sequences not detectable in finnish mesothelioma patients not exposed to SV40-contaminated polio vaccines.}, journal = {Molecular carcinogenesis}, volume = {26}, number = {2}, pages = {93-99}, pmid = {10506753}, issn = {0899-1987}, support = {CA 77220-01/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Blotting, Southern ; Cocarcinogenesis ; DNA, Viral/analysis ; Drug Contamination ; Female ; Finland ; Humans ; Male ; Mesothelioma/*virology ; Middle Aged ; Molecular Sequence Data ; Pleural Neoplasms/*virology ; Poliovirus Vaccine, Inactivated/*adverse effects ; Polymerase Chain Reaction ; Simian virus 40/*genetics/*isolation & purification ; Time Factors ; }, abstract = {Occupational asbestos exposure can be demonstrated in 80% of mesothelioma cases. A possible role of simian virus 40 (SV40) in the etiology of mesothelioma was raised because several studies reported the presence and expression of SV40-like DNA sequences in human mesotheliomas. It is also known that expression of SV40 large T antigen inhibits cellular Rb and p53. This suggests that SV40 might render infected cells more susceptible to asbestos carcinogenicity. The SV40-like sequences are suggested to have arisen from contaminated polio vaccines. Millions of people in the United States and most European countries were inoculated with SV40-contaminated polio vaccine in 1955-1963. However, in Finland, where polio vaccination started in 1957, no SV40-contaminated vaccine was used. We used a polymerase chain reaction-based method to test for the presence of SV40-like sequences in DNA extracted from the frozen tumor tissues of 49 Finnish mesothelioma patients, most of whom had been occupationally exposed to asbestos. All of the Finnish tumor tissues tested negative for SV40-like sequences. The results suggest that the SV40-like sequences detected in mesothelioma tissue in some previous studies may indeed originate from SV40-contaminated polio vaccines. It is a matter of speculation whether the absence of SV40 infection has contributed to the relatively low incidence of mesothelioma in Finland (1/10(5) in 1990-1995).}, } @article {pmid10504529, year = {1999}, author = {Watanabe, M and Suzuki, H and Fukutome, K and Enoki, A and Yamada, N and Nakano, T and Shiraishi, T and Yatani, R}, title = {An autopsy case of a malignant pericardial mesothelioma in a Japanese young man.}, journal = {Pathology international}, volume = {49}, number = {7}, pages = {658-662}, doi = {10.1046/j.1440-1827.1999.00915.x}, pmid = {10504529}, issn = {1320-5463}, mesh = {Adult ; Biomarkers, Tumor/analysis ; Desmosomes/ultrastructure ; Fatal Outcome ; Glycogen/ultrastructure ; Heart Neoplasms/chemistry/diagnostic imaging/*pathology ; Humans ; Immunoenzyme Techniques ; Lung Neoplasms/chemistry/*secondary ; Magnetic Resonance Imaging ; Male ; Mediastinal Neoplasms/chemistry/*secondary ; Mesothelioma/chemistry/diagnostic imaging/*secondary ; Microscopy, Electron ; Microvilli/ultrastructure ; Pericardial Effusion/diagnostic imaging/etiology/pathology ; Pericardium/chemistry/diagnostic imaging/*pathology ; Radiography, Thoracic ; Tight Junctions/ultrastructure ; }, abstract = {An autopsy case of a malignant pericardial mesothelioma in a 27-year-old man with no history of exposure to asbestos is reported. He was admitted for heart failure due to pericardial effusion of unknown origin and surgically drained, but later died. The diagnosis of a malignant pericardial mesothelioma was made on the basis of histologic, immunohistochemical and ultrastructural findings. The tumor was located on the pericardium, but autopsy revealed that it had spread extensively in the mediastinum and the lungs. Microscopically, the tumor cells were epithelial like and contained histochemically demonstrable glycogen and hyaluronic acid. Immunohistochemical studies of the tumor demonstrated positive immunoreactivity for cytokeratin 19, muscle actin HHF35, epithelial membrane antigen, CA125, p53 and p21WAF1/CIP1 whereas the tumor was negative for cytokeratins 10 and 17, carcinoembryonic antigen, vimentin, epithelial antigen BerEP4, S-100, c-erbB2 and bcl-2. A high MIB-1 labeling index was noted. Under the electron microscope the tumor cells exhibited long, thin villi. The operation and autopsy findings thus revealed this to be a very rare case of malignant pericardial mesothelioma in a young man.}, } @article {pmid10500343, year = {1999}, author = {Morse, T and Storey, E}, title = {Fatalities from occupational diseases in Connecticut.}, journal = {Connecticut medicine}, volume = {63}, number = {8}, pages = {463-466}, pmid = {10500343}, issn = {0010-6178}, mesh = {Asbestosis/mortality ; Cardiovascular Diseases/mortality ; Cause of Death ; Connecticut ; Death Certificates ; Humans ; Mesothelioma/mortality ; Occupational Diseases/*mortality ; Pleural Neoplasms/mortality ; Pneumoconiosis/mortality ; Registries ; Silicosis/mortality ; United States ; United States Occupational Safety and Health Administration ; }, abstract = {Occupational diseases in Connecticut were identified using reports to the Workers' Compensation Commission, Connecticut OSHA, Vital Statistics, and the Tumor Registry. There were 93 identified fatalities from occupational disease in 1995, and 90 in 1994, approximately three times the number of traumatic occupational fatalities. Identified fatalities were predominantly from asbestos-related diseases, including mesothelioma and asbestosis. Most occupational diseases are not readily identifiable with current reporting mechanisms. Based on national estimates, these figures are considered to be an underestimate of the true burden of occupational disease. Increased awareness and reporting of occupational diseases is needed to properly identify and prevent these common conditions.}, } @article {pmid10493306, year = {1999}, author = {Janssen-Heijnen, ML and Damhuis, RA and Klinkhamer, PJ and Schipper, RM and Coebergh, JW}, title = {Increased but low incidence and poor survival of malignant mesothelioma in the southeastern part of The Netherlands since 1970: a population-based study.}, journal = {European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP)}, volume = {8}, number = {4}, pages = {311-314}, doi = {10.1097/00008469-199908000-00007}, pmid = {10493306}, issn = {0959-8278}, mesh = {Adult ; Aged ; Female ; Humans ; Incidence ; Male ; Mesothelioma/epidemiology/*mortality ; Middle Aged ; Netherlands/epidemiology ; Peritoneal Neoplasms/epidemiology/*mortality ; Pleural Neoplasms/epidemiology/*mortality ; Registries/statistics & numerical data ; Survival Rate ; Testicular Neoplasms/epidemiology/mortality ; }, abstract = {Changes in the incidence and survival rates for malignant mesothelioma in the southeastern part of The Netherlands since 1970 were investigated, using data from the Eindhoven Cancer Registry (ECR). The exposure to asbestos in this area is presumed to be limited. Most of the mesotheliomas occurred in the pleura, where there were 119 (88%) against 15 (11%) in the peritoneum and two in the tunica vaginalis testis. Compared to other European countries, the incidence rate for the southeastern part of The Netherlands was fairly low in the second half of the 1980s. Between 1975 and 1994 the age-adjusted incidence rates (ESR) for pleural mesothelioma increased twofold (from 10 to 19 per one million person-years among men and from 2.4 to 3.8 among women). The rate for peritoneal mesothelioma remained constant. The overall relative 0.5-, 1-, and 3-year survival rates remained 68, 42, and 8%, respectively. The fourfold higher incidence rate for men compared with women reflects the fact that mesothelioma is mainly an occupational disease. In view of presumed limited exposure to asbestos and small geographical variation, the incidence of mesothelioma in the southeastern part of The Netherlands will probably remain low, despite an increase in the past decades.}, } @article {pmid10492646, year = {1999}, author = {Hillerdal, G}, title = {Mesothelioma: cases associated with non-occupational and low dose exposures.}, journal = {Occupational and environmental medicine}, volume = {56}, number = {8}, pages = {505-513}, pmid = {10492646}, issn = {1351-0711}, mesh = {Asbestos/*adverse effects ; Environmental Exposure/*adverse effects ; Female ; Humans ; Male ; Maximum Allowable Concentration ; Mesothelioma/*etiology/mortality ; Occupational Exposure/adverse effects ; Risk Assessment ; }, abstract = {OBJECTIVES: To estimate the importance of low dose exposure to asbestos on the risk of mesothelioma.

METHODS: A review of the literature.

RESULTS AND CONCLUSIONS: There is no evidence of a threshold level below which there is no risk of mesothelioma. Low level exposure more often than not contains peak concentrations which can be very high for short periods. There might exist a background level of mesothelioma occurring in the absence of exposure ot asbestos, but there is no proof of this and this "natural level" is probably much lower than the 1-2/million/year which has been often cited.}, } @article {pmid10489674, year = {1999}, author = {Heki, U and Fujimura, M and Kasahara, K and Matsubara, F and Matsuda, T}, title = {Malignant mesothelioma presenting as pulmonary metastasis ahead of growth of primary tumour.}, journal = {Respirology (Carlton, Vic.)}, volume = {4}, number = {3}, pages = {279-281}, doi = {10.1046/j.1440-1843.1999.00190.x}, pmid = {10489674}, issn = {1323-7799}, mesh = {Female ; Humans ; Lung Neoplasms/*secondary ; Mediastinal Neoplasms/diagnosis/*pathology ; Mesothelioma/*secondary ; Middle Aged ; Time Factors ; }, abstract = {A 59-year-old woman was admitted to Houju Memorial Hospital, Ishikawa, Japan, because of cough and fever on 30 March 1997. A diagnosis of pneumonia was made and she was given antibiotics. Her symptoms improved but failed to resolve completely on antibiotic therapy. On 9 September 1997, she revisited the hospital because of bodyweight loss and malaise. There was no history of exposure to asbestos. The chest roentgenogram revealed infiltrative shadows with vague and indistinct margins suggesting inflammatory processes, which were more extensive than those investigated on her last visit. One month later, a giant tumour was detected rapidly growing from the mediastinum and open biopsy was performed. The histological examination confirmed that the tumour was a malignant mesothelioma and the intrapulmonary nodules were its metastases. This is a rare case of pulmonary metastasis being present for several months before an appearance of primary mesothelioma.}, } @article {pmid10481335, year = {1999}, author = {Jover-Sáenz, A and Vilà-Justribó, M and Salud-Salvià, A and Porcel-Pérez, JM and Vicente de Vera, P}, title = {[Malignant pleural mesothelioma with an unusual radiologic manifestation].}, journal = {Anales de medicina interna (Madrid, Spain : 1984)}, volume = {16}, number = {7}, pages = {354-356}, pmid = {10481335}, issn = {0212-7199}, mesh = {Calcinosis/diagnostic imaging ; Humans ; Male ; Mesothelioma/*diagnostic imaging ; Middle Aged ; Pleura/diagnostic imaging ; Pleural Diseases/diagnostic imaging ; Pleural Neoplasms/*diagnostic imaging ; Radiography, Abdominal ; Radiography, Thoracic ; Tomography, X-Ray Computed ; }, abstract = {The malignant pleural mesothelioma is a rare neoplastic consequence observed in people with previous exposition to asbestos essentially. The malignant mesothelioma like a term, not only reports to primary malignant extended tumors that are derived of pleural mesothelioma but also, pericardial and peritoneal (about 20%). The exposition of asbestos stands for a sequential cellular reaction with oncogenic potential and with a typical majority clinical presentation. We described the case a patient complaint of malignant pleural mesothelioma with unusual radiology presentation with the result that unilateral calcified pleural plaques with pleural thickening and pleural effusion absence. Definitive diagnostic was achieved by thoracotomy.}, } @article {pmid10478545, year = {1999}, author = {Yuasa, H and Tomoyasu, M}, title = {[Clinical comparison of diffuse malignant mesothelioma of the pleura and pseudomesotheliomatous carcinoma of the lung for each case].}, journal = {Kyobu geka. The Japanese journal of thoracic surgery}, volume = {52}, number = {10}, pages = {836-839}, pmid = {10478545}, issn = {0021-5252}, mesh = {Adult ; Diagnosis, Differential ; Humans ; Lung Neoplasms/*diagnosis/pathology/surgery ; Male ; Mesothelioma/*diagnosis/pathology/surgery ; Middle Aged ; Pleural Neoplasms/*diagnosis/pathology/surgery ; }, abstract = {Because we experienced each 1 operative case of diffuse malignant mesothelioma of the pleura and pseudomesotheliomatous carcinoma of the lung discovered with pleural effusion, clinical comparison investigated both. The first case was suspected diffuse malignant mesothelioma of the pleura before operation, and we performed pleuropneumonectomy. But the pathologic diagnosis was adenocarcinoma of the lung, what is so called pseudomesotheliomatous carcinoma. The second case had inhaled asbestos and his pleural effusion revealed high concentrations of hyaluronic acid. Thoracoscopic biopsy showed malignant mesothelioma, and we performed pleuropneumonectomy. The pathologic final diagnosis was diffuse malignant mesothelioma of the pleura. In clinical differential diagnosis of diffuse malignant mesothelioma of the pleura and pseudomesotheliomatous carcinoma of the lung, history of inhalation of asbestos and concentrations of hyaluronic acid in pleural effusion are helpful. And thoracoscopic biopsy is necessary in established diagnosis.}, } @article {pmid10477659, year = {1999}, author = {McConnell, EE and Axten, C and Hesterberg, TW and Chevalier, J and Miiller, WC and Everitt, J and Oberdörster, G and Chase, GR and Thevenaz, P and Kotin, P}, title = {Studies on the inhalation toxicology of two fiberglasses and amosite asbestos in the Syrian golden hamster. Part II. Results of chronic exposure.}, journal = {Inhalation toxicology}, volume = {11}, number = {9}, pages = {785-835}, doi = {10.1080/089583799196754}, pmid = {10477659}, issn = {0895-8378}, mesh = {Animals ; Asbestos, Amosite/administration & dosage/*toxicity ; Body Burden ; Body Weight/drug effects ; Bronchoalveolar Lavage Fluid/chemistry/cytology ; Carcinogens/administration & dosage/*toxicity ; Cell Division/drug effects ; Cricetinae ; *Glass ; Inhalation Exposure/*adverse effects ; Lung/metabolism/*pathology ; Lung Diseases/chemically induced/pathology ; Male ; Mesocricetus ; Mineral Fibers/*toxicity ; Models, Animal ; Organ Size/drug effects ; Pleura/pathology ; Time Factors ; }, abstract = {Fiberglass (FG) is the largest category of man-made mineral fibers (MMVFs). Many types of FG are manufactured for specific uses building insulation, air handling, filtration, and sound absorption. In the United States, > 95% of FG produced is for building insulation. Several inhalation studies in rodents of FG building insulation have shown no indication of pulmonary fibrosis or carcinogenic activity. However, because of increasing use and potential for widespread human exposure, a chronic toxicity/carcinogenicity inhalation study of a typical building insulation FG (MMVF 10a) was conducted in hamsters, which were shown to be highly sensitive to the induction of mesotheliomas with another MMVF. A special-application FG (MMVF 33) and amosite asbestos were used for comparative purposes. Groups of 140 weanling male Syrian golden hamsters were exposed via nose-only inhalation for 6 h/day, 5 days/wk for 78 wk to either filtered air (chamber controls) or MMVF 10a, MMVF 33, or amosite asbestos at 250-300 WHO fibers/cm(3) with two additional amosite asbestos groups at 25 and 125 WHO fibers/cm(3). They were then held unexposed for 6 wk until approximately 10-20% survival. After 13, 26, 52, and 78 wk, various pulmonary parameters and lung fiber burdens were evaluated. Groups hamsters were removed from exposure at 13 and 52 wk and were held until 78 wk (recovery groups). Initial lung deposition of long fibers (>20 microm in length) after a single 6-h exposure was similar for all 3 fibers exposed to 250-300 fibers/cm(3). MMVF 10a lungs showed inflammation (which regressed in recovery hamsters) but no pulmonary or pleural fibrosis or neoplasms. MMVF 33 induced more severe inflammation and mild interstitial and pleural fibrosis by 26 wk that progressed in severity until 52 wk, after which it plateaued. While the inflammatory lesions regressed in the recovery animals, pulmonary or pleural fibrosis did not. A single multicentric mesothelioma was observed at 32 wk. No neoplasms were found in the remainder of the study. Amosite asbestos produced dose-related inflammation and pulmonary and pleural fibrosis as early as 13 wk in all 3 exposure levels. The lesions progressed during the course of the study, and at 78 wk severe pulmonary fibrosis with large areas of consolidation was observed in the highest 2 exposure groups. Progressive pleural fibrosis with mesothelial hypertrophy and hyperplasia was present in the thoracic wall and diaphragm in most animals and increased with time in the recovery hamsters. While no pulmonary neoplasms were observed in the amosite exposed hamsters, a large number of mesotheliomas were found; 25 fibers/cm(3), 3.6%; 125 fibers/cm(3), 25.9%; and 250 fibers/cm(3), 19.5%. For the 3 fiber types, the severity of the lung and pleural lesions generally paralleled the cumulative fiber burden, especially those >20 microm length, in the lung, thoracic wall, and diaphragm. They also inversely paralleled the in vitro dissolution rates; that is, the faster the dissolution, the lower were the cumulative lung burdens and the less severe the effects.}, } @article {pmid10477658, year = {1999}, author = {Hesterberg, TW and Axten, C and McConnell, EE and Hart, GA and Miiller, W and Chevalier, J and Everitt, J and Thevenaz, P and Oberdörster, G}, title = {Studies on the inhalation toxicology of two fiberglasses and amosite asbestos in the syrian golden hamster. Part I. Results of a subchronic study and dose selection for a chronic study.}, journal = {Inhalation toxicology}, volume = {11}, number = {9}, pages = {747-784}, doi = {10.1080/089583799196745}, pmid = {10477658}, issn = {0895-8378}, mesh = {Aerosols ; Animals ; Asbestos, Amosite/administration & dosage/*toxicity ; Body Burden ; Body Weight/drug effects ; Bronchoalveolar Lavage Fluid/chemistry/cytology ; Carcinogens/administration & dosage/*toxicity ; Cell Division/drug effects ; Cricetinae ; *Glass ; Inhalation Exposure/*adverse effects ; Lung/*pathology ; Lung Diseases/chemically induced/pathology ; Male ; Mesocricetus ; Microspheres ; Mineral Fibers/*toxicity ; Models, Animal ; Organ Size/drug effects ; Time Factors ; }, abstract = {A multidose, subchronic inhalation study was used to estimate the maximum tolerated dose (MTD) of 901 fiberglass (MMVF10.1) for a chronic inhalation study using hamsters. Subchronic study results indicated that 30 mg/m(3) [250-300 WHO fibers (>5 microm long)/cm(3) and 100-130 fibers/cm(3) >20 microm long] meets or exceeds the estimated MTD, and chronic study results confirmed this. For the subchronic study, hamsters were exposed 6 h/day, 5 days/wk, for 13 wk to MMVF10.1 at 3, 16, 30, 45, and 60 mg/m(3) (36, 206, 316, 552, or 714 WHO fibers/cm(3)), then monitored for 10 wk. Results demonstrating MTD were: inflammatory response (all fiber exposures); elevated lung cell proliferation with @ges;16 mg/m(3); lung lavage neutrophil elevations with @ges;16 mg/m(3) and lactate dehydrogenase (LDH) and protein elevations with > or = 30 mg/m(3); and persistent abnormal macrophage/fiber clumps in lungs exposed to 45 and 60 mg/m(3), which suggest overloading of clearance mechanisms. For the chronic study, hamsters were exposed for 78 wk to MMVF10a (901 fiber glass) or MMVF33 (special-application 475 fiberglass) at approximately 300 WHO fibers/cm(3) (approximately 100 fibers/cm(3) @gt;20 @mu;m long), or to amosite asbestos at an equivalent concentration and 2 lower concentrations. All fiber-exposed animals had pulmonary inflammation, elevated lung lavage cells, and increased lung cell proliferation. Between 52 and 78 wk of exposure, lung burdens of all fibers increased at an accelerated rate, suggesting impairment of clearance mechanisms. MMVF33 and amosite induced fibrosis and pleural mesothelioma. These findings substantiate that exposures in the chronic study adequately tested the toxic potential of fiberglass.}, } @article {pmid10474522, year = {1999}, author = {Mayall, FG and Jacobson, G and Wilkins, R}, title = {Mutations of p53 gene and SV40 sequences in asbestos associated and non-asbestos-associated mesotheliomas.}, journal = {Journal of clinical pathology}, volume = {52}, number = {4}, pages = {291-293}, pmid = {10474522}, issn = {0021-9746}, mesh = {Asbestos/*adverse effects ; DNA, Viral/analysis ; Genes, p53/*genetics ; Humans ; Immunohistochemistry ; Lung Neoplasms/etiology/*genetics ; Mesothelioma/etiology/*genetics ; Microscopy, Electron ; Mineral Fibers/analysis ; Mutation ; Polymerase Chain Reaction ; Polymorphism, Single-Stranded Conformational ; Simian virus 40/*genetics ; }, abstract = {AIM: To examine mesotheliomas for a possible relation between p53 immunostaining, p53 gene mutation, simian virus 40 (SV40), and asbestos exposure.

METHODS: Paraffin sections from 11 mesotheliomas were used for p53 immunostaining and also to extract DNA. This was analysed for the presence of mutations in exons 5 to 8 of the p53 gene using a "cold" single strand conformational polymorphism method, together with sequencing. The DNA from the paraffin sections was also used to search for SV40 sequences. A 105 base pair segment at the 3' of the SV40 large T antigen (Tag) was targeted and any PCR amplification products were sequenced to confirm that they were of SV40 origin. EDAX electron microscopic differential mineral fibre counts were performed on dried lung tissue at a specialist referral centre.

RESULTS: The fibre counts showed that seven of the mesotheliomas were associated with abnormally high asbestos exposure. Of these, two showed p53 immunostaining, none showed p53 gene mutation, and five showed SV40. Of the four other mesotheliomas, three showed p53 immunostaining, one showed a (silent) p53 mutation, and none showed SV40. The difference in frequency of SV40 detection was significant at the p < 0.05 level.

CONCLUSIONS: Immunostaining for the p53 gene was relatively common but p53 mutations were rare in this series. SV40 virus sequence was detected in five of seven asbestos associated mesotheliomas but in none of the non-asbestos-associated mesotheliomas. This suggests there may be a synergistic interaction between asbestos and SV40 in human mesotheliomas. A study with a larger number of cases is needed to investigate these observations further.}, } @article {pmid10471051, year = {1999}, author = {Schneider, J and Presek, P and Braun, A and Bauer, P and Konietzko, N and Wiesner, B and Woitowitz, HJ}, title = {p53 protein, EGF receptor, and anti-p53 antibodies in serum from patients with occupationally derived lung cancer.}, journal = {British journal of cancer}, volume = {80}, number = {12}, pages = {1987-1994}, pmid = {10471051}, issn = {0007-0920}, mesh = {Adenocarcinoma/blood/etiology ; Aged ; Autoantibodies/*blood ; Biomarkers, Tumor/*blood ; Carcinoma, Large Cell/blood/etiology ; Carcinoma, Small Cell/blood/etiology ; Carcinoma, Squamous Cell/blood/etiology ; ErbB Receptors/*blood ; Humans ; Lung Diseases/*blood/etiology ; Lung Neoplasms/*blood/etiology/secondary ; Male ; Mesothelioma/blood/etiology ; Middle Aged ; *Occupational Exposure ; Pleural Effusion/*blood/etiology ; Pleural Neoplasms/blood/etiology ; Pulmonary Fibrosis/blood/etiology ; Reference Values ; Tumor Suppressor Protein p53/*blood/immunology ; }, abstract = {The oncogene product epidermal growth factor receptor (EGF-R), the tumour suppressor gene product p53 and anti-p53 antibodies are detectable in the serum of certain cancer patients. Increased levels of some of these products were reported in lung cancer patients after occupational asbestos exposure and after exposure to polycyclic aromatic hydrocarbons or vinylchloride. In the first step, this study investigated the possible diagnostic value of serum EGF-R, p53-protein and anti-p53 antibodies, measured by an enzyme-linked immunosorbent assay, in lung tumour patients. In addition to being investigated on a molecular epidemiological basis, these parameters were examined as biomarkers of carcinogenesis, especially with regard to asbestos incorporation effects or of radon-induced lung cancers. Also, a possible effect of cigarette smoking and age dependence were studied. A total of 116 male patients with lung or pleural tumours were examined. The histological classification was four small-cell cancers, six large-cell cancers, 32 adenocarcinomas, 47 squamous carcinomas, 12 mixed lung carcinomas, five diffuse malignant mesotheliomas and ten lung metastasis of extrapulmonary tumours. Twenty-two lung cancers and all mesotheliomas were related to asbestos, 22 lung cancers were related to ionizing radiation and 61 patients had cigarette smoke-related lung cancer. Besides these patients 50 male patients with non-malignant lung or pleural diseases were included; of the latter eight subjects suffered from asbestosis. Controls were 129 male subjects without any lung disease. No significantly elevated or decreased serum values for p53 protein, EGF-R, or anti-p53 antibodies as a function of histological tumour type, age, or degree and type of exposure (asbestos, smoking, ionizing radiation) could be found. The utility of p53-protein, EGF-R and anti-p53 antibodies as routine biomarkers for screening occupationally derived lung cancers is limited.}, } @article {pmid10464903, year = {1999}, author = {Metintas, M and Ozdemir, N and Hillerdal, G and Uçgun, I and Metintas, S and Baykul, C and Elbek, O and Mutlu, S and Kolsuz, M}, title = {Environmental asbestos exposure and malignant pleural mesothelioma.}, journal = {Respiratory medicine}, volume = {93}, number = {5}, pages = {349-355}, doi = {10.1016/s0954-6111(99)90318-9}, pmid = {10464903}, issn = {0954-6111}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects/analysis ; Environmental Exposure/*adverse effects ; Female ; Humans ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Pleural Diseases/*epidemiology/etiology ; Prospective Studies ; Risk Factors ; Rural Population/statistics & numerical data ; Turkey/epidemiology ; }, abstract = {Asbestos-related benign and malignant pleural diseases are endemic in some rural parts of central Turkey because of environmental exposure to asbestos fibres. We report here epidemiological data on 113 patients with diffuse malignant pleural mesothelioma (DMPM) diagnosed in our clinic in Eskişehir, located in central Turkey. Of the 113 patients, 59 were men and 54 women (male:female ratio = 1). Ninety-seven patients (86%) had non-occupational asbestos exposure; all were living in villages. Their mean age was 56 years. As the patients had been exposed to asbestos from birth, the latency period was equivalent to the age of the patients. Twenty-eight patients (29%) had lived in villages their entire lives. The other 69 (71%) had been born in a village but migrated to the city or had given up white-soil usage for various reasons. The mean exposure time was 55 years for those with a long exposure period and 25 years for those with a short exposure period, but there was no significant difference between the age of the disease appearance for both groups (55 and 56 years, respectively). Thus, the latency time of mesothelioma due to environmental exposure to asbestos was longer than that due to occupational exposure, but independent of the length of exposure. Soil samples from 67 villages were analysed, comprising a population of 10,120 villagers. Tremolite and some other types of asbestos were found. In conclusion, DMPM in our region is due to mainly to environmental exposure to asbestos. The risk is substantial as a large proportion of the villagers are exposed. After smoking, asbestos exposure is one of the most serious health hazards in our rural population.}, } @article {pmid10461539, year = {1999}, author = {Livneh, A and Langevitz, P and Pras, M}, title = {Pulmonary associations in familial Mediterranean fever.}, journal = {Current opinion in pulmonary medicine}, volume = {5}, number = {5}, pages = {326-331}, doi = {10.1097/00063198-199909000-00011}, pmid = {10461539}, issn = {1070-5287}, mesh = {Amyloidosis/complications ; Asthma/etiology ; Familial Mediterranean Fever/*complications/physiopathology ; Hemorrhage/etiology ; Humans ; Infarction/etiology ; Lung/blood supply ; Lung Diseases, Interstitial/*etiology ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Pleurisy/etiology ; Serositis/etiology ; Vasculitis/complications ; }, abstract = {Familial Mediterranean fever (FMF) is a hereditary periodic fever syndrome expressed by acute episodes of fever and painful manifestations. In this report, the pulmonary manifestations of FMF are reviewed, the most prominent of which are chest attacks due to pleuritis. Nephropathic amyloidosis of the AA type, which complicates FMF in most untreated patients, may progress to affect other organs, including the lungs, but this rarely produces noticeable symptoms. The common association between FMF and vasculitis makes pulmonary hemorrhage, infarction, or infiltrates highly possible. These complications, however, have been reported only rarely. Asthma was found to occur less often than expected in patients with FMF, but methodologic faults make this finding doubtful. Finally, the occurrence of mesothelioma in five patients with FMF who were not exposed to asbestos suggests a role for recurrent FMF serositis in the pathogenesis of this malignancy.}, } @article {pmid10448326, year = {1999}, author = {Divine, BJ and Hartman, CM and Wendt, JK}, title = {Update of the Texaco mortality study 1947-93: Part II. Analyses of specific causes of death for white men employed in refining, research, and petrochemicals.}, journal = {Occupational and environmental medicine}, volume = {56}, number = {3}, pages = {174-180}, pmid = {10448326}, issn = {1351-0711}, mesh = {Brain Neoplasms/etiology/mortality ; Cause of Death ; Chemical Industry/*statistics & numerical data ; Cohort Studies ; Humans ; Leukemia/etiology/mortality ; Lymphoma, Non-Hodgkin/etiology/mortality ; Male ; Mesothelioma/etiology/mortality ; Multiple Myeloma/etiology/mortality ; Neoplasms/etiology/*mortality ; Occupational Diseases/etiology/*mortality ; *Petroleum ; Research Personnel/statistics & numerical data ; Texas/epidemiology ; }, abstract = {OBJECTIVE: To examine patterns of mortality for specific causes of death with increases in the Texaco mortality study to determine if the patterns are related to employment in the petroleum industry.

METHODS: Mortality patterns by duration of employment in various job groups were examined for mesothelioma, non-Hodgkin's lymphoma, multiple myeloma, cell type specific leukaemia, and brain tumours.

RESULTS: Mortality from mesothelioma was examined for the total cohort and for two maintenance groups with the greatest potential for exposure to asbestos. The insulator group had a standardised mortality ratio (SMR) of 3029, and a larger group consisting of insulators, carpenters, labourers, electricians, pipefitters, boiler-makers, and welders had an SMR of 411. The mortalities from mesothelioma increased with increasing duration of employment. Mortality was lower for those first employed after 1950. An analysis of all brain tumours for the total cohort and some job and unit subgroups resulted in an SMR of 178 for those employed on the units related to motor oil and 166 for those employed as laboratory workers. Mortality from brain tumours in both of these job groups was higher for those employed > or = 5 years in the group. An analysis of non-Hodgkin's lymphoma showed no consistent patterns among the various employment groups. Mortality from multiple myeloma was non-significantly increased among people employed on the crude (SMR = 155) and fluid catalytic cracking units (SMR = 198). Leukaemia mortality was not increased for the total cohort, and a cell type analysis of leukaemia mortality for the total cohort showed no significant increases for the major cell types. However, there were significant increases for acute unspecified leukaemia (SMR = 276) and leukaemia of unknown cell type (SMR = 231).

CONCLUSIONS: Analyses of specific causes of death by duration of employment in various job and process units did not show any patterns which suggest that, other than for mesothelioma, any of these increases in mortalities were likely to have resulted from workplace exposures or from employment at one of the places included in the Texaco mortality study.}, } @article {pmid10448319, year = {1999}, author = {Firth, HM and Elwood, JM and Cox, B and Herbison, GP}, title = {Historical cohort study of a New Zealand foundry and heavy engineering plant.}, journal = {Occupational and environmental medicine}, volume = {56}, number = {2}, pages = {134-138}, pmid = {10448319}, issn = {1351-0711}, mesh = {Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Cause of Death ; Cohort Studies ; Engineering/*statistics & numerical data ; Humans ; Male ; *Metallurgy ; Neoplasms/etiology/mortality ; New Zealand/epidemiology ; Occupational Diseases/etiology/*mortality ; Respiration Disorders/etiology/mortality ; }, abstract = {OBJECTIVES: To investigate the mortality of workers who had been exposed to asbestos, machining fluids and foundry work in a foundry and heavy engineering plant in the railway rolling stock manufacturing industry in New Zealand.

METHODS: Historical cohort study design.

RESULTS: For the total workforce of 3522 men employed between 1945 and 1991, follow up was 90% of person-years to 31 December 1991. Significantly increased standardised mortality ratios (SMRs) were found for all causes of death combined (SMR 1.07; 95% confidence interval (95% CI) 1.01 to 1.14), all malignancies (SMR 1.15; 95% CI 1.01 to 1.31), circulatory (SMR 1.16; 95% CI 1.07 to 1.27) and musculoskeletal diseases (SMR 3.06; 95% CI 1.39 to 5.84), all digestive cancers (SMR 1.29; 95% CI 1.04 to 1.59), all respiratory cancers (SMR 1.34; 95% CI 1.08 to 1.65), cancer of the oesophagus (SMR 1.97; 95% CI 1.01 to 3.45), and mesothelioma of the pleura (SMR 6.58; 95% CI 1.24 to 19.49). Three deaths from pleural mesothelioma were recorded, with latency times of 51, 53, and 57 years. There were no dose-response relations between exposure to asbestos, machining fluids or foundry work, or by duration of employment in the plant, and any cause of death.

CONCLUSIONS: This study found small increases in risk for several causes of death among foundry and heavy engineering workers; however, these increases were small and the possible effects of smoking and other lifestyle factors could not be excluded. There was evidence of asbestos related disease in those involved in engineering work in the past.}, } @article {pmid10448315, year = {1999}, author = {Järvholm, B and Englund, A and Albin, M}, title = {Pleural mesothelioma in Sweden: an analysis of the incidence according to the use of asbestos.}, journal = {Occupational and environmental medicine}, volume = {56}, number = {2}, pages = {110-113}, pmid = {10448315}, issn = {1351-0711}, mesh = {Adult ; Age Distribution ; Aged ; Asbestos/administration & dosage/*adverse effects ; Cohort Studies ; Female ; Humans ; Incidence ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Diseases/*epidemiology/etiology ; Occupational Exposure/adverse effects ; Pleural Neoplasms/*epidemiology/etiology ; Registries ; Sweden/epidemiology ; }, abstract = {OBJECTIVE: To investigate if the preventive measures taken to reduce the occupational exposure to asbestos have resulted in a decreased incidence of pleural mesothelioma in Sweden.

METHODS: The incidence of pleural mesothelioma between 1958 and 1995 for birth cohorts born between 1885 and 1964 was investigated. The cases of pleural mesothelioma were identified through the Swedish Cancer Register.

RESULTS: In 1995, around 80 cases of pleural mesothelioma could be attributed to occupational exposure to asbestos. There is an increasing incidence in more recent birth cohorts in men. The incidence was considerably higher in the male cohort born between 1935 and 1944 than in men born earlier.

CONCLUSIONS: The annual incidence of pleural mesothelioma attributable to occupational exposure to asbestos is today larger than all fatal occupational accidents in Sweden. The first asbestos regulation was adopted in 1964 and in the mid 1970s imports of raw asbestos decreased drastically. Yet there is no obvious indication that the preventive measures have decreased the risk of pleural mesothelioma. The long latency indicates that the effects of preventive measures in the 1970s could first be evaluated around 2005.}, } @article {pmid10446476, year = {1999}, author = {Coles, GV}, title = {A valuable service.}, journal = {Applied occupational and environmental hygiene}, volume = {14}, number = {5}, pages = {267-268}, doi = {10.1080/104732299302828}, pmid = {10446476}, issn = {1047-322X}, mesh = {Asbestos/adverse effects ; Asbestosis/*prevention & control ; Australia ; Environmental Monitoring ; Equipment Design ; Health Promotion/methods ; Humans ; Mesothelioma/etiology/prevention & control ; Occupational Exposure/*prevention & control ; *Protective Clothing ; *Respiratory Protective Devices ; }, } @article {pmid10444059, year = {1999}, author = {Kayser, K and Becker, C and Seeberg, N and Gabius, HJ}, title = {Quantitation of asbestos and asbestos-like fibers in human lung tissue by hot and wet ashing, and the significance of their presence for survival of lung carcinoma and mesothelioma patients.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {24}, number = {2}, pages = {89-98}, doi = {10.1016/s0169-5002(99)00035-5}, pmid = {10444059}, issn = {0169-5002}, mesh = {Asbestos/*analysis ; Carcinoma, Non-Small-Cell Lung/*mortality ; Female ; Humans ; Lung/*chemistry ; Lung Diseases/mortality ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; Middle Aged ; Mineral Fibers/*analysis ; Predictive Value of Tests ; Prospective Studies ; Smoking ; Survival Rate ; }, abstract = {Technical standardization on randomly chosen samples of tissue specimen is essential for the validity of interpretations derived from measurements on the presence of asbestos fibers in lung in combination with further features of the patients. Fixed non-tumorous lung tissue (2-3 g) of 150 patients after surgery for various lung diseases were either digested in 45 ml of 13% solution with sodium hypochlorite (NaClO; wet ashing) or heated in an oven at 600 degrees C for 15 min (hot ashing). After tissue disintegration asbestos and asbestos-like fibers were counted by visual inspection, and the fiber concentration in the lung parenchyma was computed. In addition, the patients' survival, and the occupational and social history were analyzed. As a result, the mean concentrations of fibers were found to be 55 f/g (fibers/gram, hot ashing) and 46 f/g (wet ashing). The difference is statistically not significant. Mesotheliomas contributed 49% (73 patients), non-small cell lung carcinomas 32% (59 patients) to the entire cohort. Eighteen patients had a non-malignant lung disease. Analysis of living habits revealed that 73 (49%) patients were heavy smokers, and 99 (66%) patients had a history of occupational asbestos exposure which lasted for 18 years on average. A statistically significant difference of the asbestos fiber concentration between the group with professional exposure and that without detectable asbestos exposure could be obtained in mesothelioma patients and non-malignant lung diseases only, and a tendency for elevated fiber presence was seen in non-small cell lung carcinoma patients. In tissue specimen of patients with non-malignant lung diseases the highest fiber concentration was measured (median 104 f/g) followed by mesothelioma patients (77 f/g), and lung carcinoma patients (62 f/g wet tissue). The difference in the fiber concentration between smokers and ex-smokers versus non-smokers was particularly high in patients with non-malignant lung diseases (103 f/g in smokers versus 33 f/g in non-smokers), still statistically significant in mesothelioma patients (100 f/g smokers versus 61 f/g non smokers), and negligible in lung carcinoma patients (58 f/g smokers versus 62 f/g non-smokers). Only 5/70 mesothelioma patients were not exposed to asbestos at work, and nearly half of the patients (36) were non-smokers. The median survival of mesothelioma patients was significantly shortened for patients with a high intrapulmonal fiber concentration greater than 70 f/g (35 weeks versus 60 weeks). This correlation was also true for lung carcinoma patients (110 weeks versus 230 weeks).}, } @article {pmid10444041, year = {1999}, author = {Chang, HY and Chen, CR and Wang, JD}, title = {Risk assessment of lung cancer and mesothelioma in people living near asbestos-related factories in Taiwan.}, journal = {Archives of environmental health}, volume = {54}, number = {3}, pages = {194-201}, doi = {10.1080/00039899909602259}, pmid = {10444041}, issn = {0003-9896}, mesh = {Adult ; Aged ; Air Pollutants/*adverse effects/analysis ; Asbestos/*adverse effects/analysis ; Asbestos, Crocidolite/adverse effects/analysis ; Child ; Environmental Exposure ; Humans ; Lung Neoplasms/*epidemiology/etiology ; Mesothelioma/*epidemiology/etiology ; Microscopy, Electron ; Microscopy, Phase-Contrast ; Middle Aged ; Models, Statistical ; Risk Assessment ; Taiwan/epidemiology ; }, abstract = {Estimates from environmental risk assessments are criticized by professionals who indicate that inaccuracies occur in exposure assessment, model selection, and determination of the population at risk. In the current study, we tackled the aforementioned issues and estimated the risks of lung cancer and mesothelioma caused by airborne asbestos among individuals who lived near asbestos factories in Taiwan. We conducted 8-h full-period samplings upwind and downwind from each factory, and we used transmission-electronic microscopy (10,000x) and phase-contrast microscopy to determine asbestos concentrations in and around each factory. We estimated the numbers of residents who lived in concentric circles of 200-m, 400-m, and 600-m diameters around each factory. A dose-response model for asbestos-induced lung cancer was adopted from a summary of seven epidemiological studies. The asbestos-mesothelioma models were patterned after the first-exposure-effect models developed by Peto and Finkelstein. The data obtained from phase-contrast microscopy significantly overestimated the risk, compared with transmission-electronic microscopy. The estimates we calculated from adopting the arithmetic mean were approximately 2-fold higher than those we calculated with the geometric mean. There were relatively low concentrations of asbestos in the study areas, thus causing an absence of a significant difference in risk estimates between different models for mesothelioma. Among the more than 20,000 residents who lived near 41 asbestos factories in Taiwan, we found that the numbers of expected excess deaths from lung cancer and mesothelioma were 5 and less than 1, respectively. We concluded that in future risk assessments for ambient asbestos exposure, investigators should adopt transmission-electronic microscopy and the geometric mean estimate. Moreover, Taiwan should enhance asbestos-control programs to assure the safety of residents who live near asbestos factories.}, } @article {pmid10443212, year = {1999}, author = {Rees, D and Goodman, K and Fourie, E and Chapman, R and Blignaut, C and Bachmann, MO and Myers, J}, title = {Asbestos exposure and mesothelioma in South Africa.}, journal = {South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde}, volume = {89}, number = {6}, pages = {627-634}, pmid = {10443212}, issn = {0256-9574}, mesh = {Asbestos, Amosite/*adverse effects ; Asbestos, Crocidolite/*adverse effects ; Carcinogens/*adverse effects ; Case-Control Studies ; Disease Outbreaks ; Female ; Humans ; Male ; Mesothelioma/diagnosis/*etiology ; Middle Aged ; Mining ; Occupational Exposure/adverse effects ; South Africa ; }, abstract = {OBJECTIVES: To describe the exposure experiences of South African mesothelioma cases, with emphasis on the contribution made to the caseload by different fibre types, the proportion of subjects with no recall of asbestos exposure and only environmental contact, and the importance of putative causes other than asbestos.

DESIGN: A multi-centred case-control study.

SUBJECTS AND SETTING: 123 patients with mesothelioma interviewed by trained interviewers in study centres established in Johannesburg, Kimberley, Pretoria, Bloemfontein, Cape Town and Port Elizabeth.

RESULTS: A convincing history of asbestos exposure was obtained in the overwhelming majority of cases (only 5 cases had unlikely asbestos exposure). Twenty-three subjects had worked on Cape crocidolite mines, 3 at Penge (an amosite mine), 3 on mines producing amosite and Transvaal crocidolite and 1 on a Transvaal crocidolite mine. Exclusively environmental exposure accounted for at least 18% of cases; 91% of these cases (20/22 subjects) had had contact with Cape crocidolite. There was a relative paucity of cases linked to amosite and no convincing chrysotile case. Non-asbestos causes occur rarely, if at all, in South Africa.

CONCLUSION: The preponderance of crocidolite cases, followed by amosite and then chrysotile cases, is consistent with the view that there is a fibre gradient of mesotheliomagenic potential for South African asbestos (crocidolite > amosite > chrysotile).}, } @article {pmid10442339, year = {1999}, author = {Grondin, SC and Sugarbaker, DJ}, title = {Malignant mesothelioma of the pleural space.}, journal = {Oncology (Williston Park, N.Y.)}, volume = {13}, number = {7}, pages = {919-26; discussion 926, 931-2}, pmid = {10442339}, issn = {0890-9091}, mesh = {Combined Modality Therapy ; Diagnosis, Differential ; Humans ; Incidence ; Magnetic Resonance Imaging ; *Mesothelioma/epidemiology/pathology/therapy ; Neoplasm Staging ; *Pleural Neoplasms/epidemiology/pathology/therapy ; Radiography, Thoracic ; Thoracoscopy ; Tomography, X-Ray Computed ; United States/epidemiology ; }, abstract = {Malignant pleural mesothelioma is an aggressive tumor associated with exposure to asbestos. Although this disease is rare, with an annual incidence in the United States of 2,000 to 3,000 cases, a steady rise in cases has been reported. Malignant pleural mesothelioma has a variable clinical presentation and may be difficult to diagnose. Pathologically, the disease is subdivided into three microscopic subtypes: epithelial, sarcomatous, and mixed histologies. Although there is no widely accepted staging system for mesothelioma, the Butchart, TNM, and Brigham staging systems have been used most commonly. Diffuse malignant pleural mesothelioma is resistant to standard modes of therapy and, if untreated, results in death 4 to 12 months from the time of diagnosis. For selected patients, an aggressive approach combining radical surgery with chemotherapy and radiotherapy has demonstrated a long-term survival advantage. New and innovative therapeutic modalities are presently being investigated in an attempt to provide viable alternatives for patients with early and advanced disease.}, } @article {pmid10441977, year = {1999}, author = {Verpeut, A and Vansteenkiste, J and Deschepper, K and Demedts, M}, title = {Preoperative work-up of a solitary diaphragmatic mass in a patient with right shoulder pain: a case for diagnosis.}, journal = {Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace}, volume = {54}, number = {3}, pages = {234-236}, pmid = {10441977}, issn = {1122-0643}, mesh = {Asbestos/adverse effects ; Diagnosis, Differential ; Fatal Outcome ; Humans ; Magnetic Resonance Imaging ; Male ; Mesothelioma/*diagnosis/etiology ; Middle Aged ; Pleural Neoplasms/*diagnosis/etiology ; Shoulder Pain/etiology ; Thoracoscopy/methods ; Tomography, X-Ray Computed ; }, abstract = {A patient presented with right shoulder pain. Imaging studies revealed an apparently solitary soft tissue pleural lesion, accompanied by a very small pleural effusion. On medical thoracoscopy, a diffuse malignant pleural mesothelioma was found. Thoracoscopy proved to play an essential part in the diagnostic work-up, avoiding a futile thoracotomy for a presumed solitary soft tissue tumour.}, } @article {pmid10441898, year = {1999}, author = {Landrigan, PJ and Nicholson, WJ and Suzuki, Y and Ladou, J}, title = {The hazards of chrysotile asbestos: a critical review.}, journal = {Industrial health}, volume = {37}, number = {3}, pages = {271-280}, doi = {10.2486/indhealth.37.271}, pmid = {10441898}, issn = {0019-8366}, mesh = {Asbestos/*adverse effects ; Asbestosis/epidemiology/*etiology ; Humans ; Lung Neoplasms/epidemiology/*etiology ; Mesothelioma/epidemiology/*etiology ; Occupational Exposure/adverse effects ; Risk Factors ; }, abstract = {Chrysotile, or "white", asbestos is the dominant form of asbestos in international commerce today. It accounts for 99% of current world asbestos production of 2 million tonnes. Chrysotile is an extremely hazardous material. Clinical and epidemiologic studies have established incontrovertibly that chrysotile causes cancer of the lung, malignant mesothelioma of the pleura and peritoneum, cancer of the larynx and certain gastrointestinal cancers. Chrysotile also causes asbestosis, a progressive fibrous disease of the lungs. Risk of these diseases increases with cumulative lifetime exposure to chrysotile and rises also with increasing time interval (latency) since first exposure. Comparative analyses have established that chrysotile is 2 to 4 times less potent than crocidolite asbestos in its ability to cause malignant mesothelioma, but of equal potency of causation of lung cancer. The International Agency for Research on Cancer of the World Health Organization has declared chrysotile asbestos a proven human carcinogen. Sales of chrysotile asbestos have virtually ended in Western Europe and North America, because of widespread recognition of its health hazards. However, asbestos sales remain strong in Japan, across Asia and in developing nations worldwide. The claim has been made that chrysotile asbestos can be used "safely" under "certain conditions" in those nations. That claim is not accurate. The Collegium Ramazzini, an international learned society in environmental and occupational medicine, has called for an immediate worldwide ban on all sales and uses of all forms of asbestos, including chrysotile. The rationale for this ban is threefold: (1) that safer substitute materials are readily available, (2) that "controlled" use of asbestos is not possible, and (3) that the health risks of asbestos are not acceptable in either the industrialized or the newly industrializing nations.}, } @article {pmid10441253, year = {1999}, author = {Iscovich, J and Fischbein, A and Witt-Kushner, J and Ginsberg, G and Richter, E and Tulchinsky, T}, title = {Malignant mesothelioma in Israel, 1961-1992.}, journal = {International journal of occupational and environmental health}, volume = {5}, number = {3}, pages = {157-163}, doi = {10.1179/oeh.1999.5.3.157}, pmid = {10441253}, issn = {1077-3525}, mesh = {Adolescent ; Adult ; Age Distribution ; Age of Onset ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Child ; Child, Preschool ; Emigration and Immigration/statistics & numerical data ; Environmental Exposure/*adverse effects ; Female ; Humans ; Incidence ; Israel/epidemiology ; Jews/statistics & numerical data ; Male ; Mesothelioma/diagnosis/*epidemiology/*etiology ; Middle Aged ; Occupational Diseases/diagnosis/*epidemiology/*etiology ; Population Surveillance ; Registries ; Residence Characteristics/statistics & numerical data ; Risk Factors ; Sex Distribution ; }, abstract = {The authors monitored time trends in the incidences and distributions of malignant mesotheliomas during 1961-92 in 223 Israeli persons, including 21 men from a cohort of 3,057 asbestos-cement workers (83,122 person-years). The annual incidence rates of malignant mesotheliomas in Jewish men ranged between 2.5 per million in 1961-82 and 4.6 per million in 1985-92. The male-to-female incidence ratio rose from 1.2 in the 1960s to 2.9 during 1985-92, as a result of increases in risk among Israeli-born males. Females accounted for 37.6% of all cases, after exclusion of the cohort of asbestos workers. Of the 223 cases, 202 (91%) had no indication of direct occupational exposure to asbestos. In Jewish females, the incidence of malignant mesotheliomas did not increase after 1961. The mean age at diagnosis in all cases was lowest in the Israeli-born (53.0 years). High levels of asbestos exposure in the 1970s and the relatively early age of onset of the disease indicate that exposure began at a younger age in Israel than in European countries. Asbestos manufacture and use peaked in Israel during the mid-1970s, so the maximum impact of these trends has yet to be seen.}, } @article {pmid10437690, year = {1999}, author = {Ng, CS and Munden, RF and Libshitz, HI}, title = {Malignant pleural mesothelioma: the spectrum of manifestations on CT in 70 cases.}, journal = {Clinical radiology}, volume = {54}, number = {7}, pages = {415-421}, doi = {10.1016/s0009-9260(99)90824-3}, pmid = {10437690}, issn = {0009-9260}, mesh = {Adult ; Aged ; Female ; Humans ; Lung Diseases/diagnostic imaging/etiology ; Male ; Mesothelioma/complications/*diagnostic imaging ; Middle Aged ; Neoplasm Invasiveness ; Pleural Diseases/diagnostic imaging ; Pleural Neoplasms/complications/*diagnostic imaging ; Retrospective Studies ; *Tomography, X-Ray Computed ; }, abstract = {AIM: The aim of this pictorial review is to illustrate the spectrum of manifestations on computed tomography (CT) of malignant pleural mesothelioma. Malignant pleural mesothelioma is the most common primary neoplasm of the pleura, but nevertheless is a rare tumour. It has a strong association with previous occupational exposure to asbestos and has a bleak prognosis.

MATERIALS AND METHODS: The pre-treatment CT findings of 70 patients at our institution, and the subsequent findings of the 35 patients who had follow-up CT, have been reviewed by three observers by consensus. 16 patients had surgical resections.

RESULTS: The most common pre-treatment findings were pleural thickening (94%) and pleural effusions (76%). Both contraction (27%) and enlargement (10%) of the ipsilateral hemithorax were identified. Extension of disease to the chest wall, mediastinum, thoracic lymph nodes, and below the diaphragm were identified. Concurrent bilateral pleural calcification and plaques indicative of previous asbestos exposure were identified in 16% of patients. CT failed to identify chest wall and mediastinal invasion in a number of patients who underwent surgical resections.

CONCLUSION: CT plays an important role in the diagnosis, assessment, and evaluation of treatment response of this tumour, although it has some limitations in specific areas in evaluating patients for surgical resection.}, } @article {pmid10434528, year = {1999}, author = {}, title = {[Reporting and compensation of mesothelioma caused by occupational exposure to asbestos in Romagna (1986-1994). Work Group for Surveillance of Mesothelioma in Romagna].}, journal = {La Medicina del lavoro}, volume = {90}, number = {3}, pages = {460-472}, pmid = {10434528}, issn = {0025-7818}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Female ; Humans ; Italy/epidemiology ; Male ; Mesothelioma/diagnosis/*etiology ; Middle Aged ; *Occupational Exposure ; Pleural Neoplasms/diagnosis/*etiology ; Population Surveillance ; Sex Factors ; *Workers' Compensation ; }, abstract = {A working group for the surveillance of mesothelioma was established in the Romagna Region of Italy. For the present report of the early data on compensation, 94 cases notified to the Romagna Cancer Registry between 1986 and 1994 (mean age, 66.7 years; male: female ratio, 1.8; frequency of pleural location, 76%; frequency of cyto-histologic confirmation, 79%) were considered. Information on asbestos exposure, occupational history, and compensation status was obtained from the patients or their relatives, the general practitioners, the local occupational health services, the National Institute of Social Insurance, the National Board for Insurance against Industrial Accidents (INAIL), and the Trade Unions. Asbestos exposure was associated with 42/94 cases (45%). Of these, 11 (26%) had been reported to INAIL. All such cases had cyto-histological confirmation. The greater frequency of reporting was found among cases known to the occupational health service (7/7) as well as those with definite, documented asbestos exposure (9/13). Only two cases had been reported by hospital physicians. Seven cases were compensated. In addition to cyto-histological confirmation, also the male sex, patient's age under the mean of 66, pleural location, and documented asbestos exposure were found to be prerequisites for compensation. Not only in these subgroups but also among cases known to the occupational health service as well as those diagnosed in 1990-94, most cases reported were compensated. These early data suggest that a more accurate diagnostic process as associated with prompt notification to the occupational health service for thorough assessment of asbestos exposure may improve the compensation process.}, } @article {pmid10434462, year = {1999}, author = {Iovino, F and Lojodice, F and Cimmino, F}, title = {[Pleural plaque fibrosis: a clinical case].}, journal = {Annali italiani di chirurgia}, volume = {70}, number = {2}, pages = {273-276}, pmid = {10434462}, issn = {0003-469X}, mesh = {Asbestosis/*diagnosis/surgery ; Biopsy, Needle ; Chronic Disease ; Humans ; Lung/diagnostic imaging ; Male ; Middle Aged ; Pleura/diagnostic imaging/pathology ; Pleural Diseases/*diagnosis/surgery ; Pulmonary Fibrosis/*diagnosis/surgery ; Tomography, X-Ray Computed ; }, abstract = {A recent case of pleural plaques fibrosis in a worker exposed since 20 years to asbestos induced us to report our experience. A 52-year-old man was seen because of chest multiple opaques of soft tissue density without any symptoms. The CT-scan of thorax with i.v. contrast showed multiple lesions of diameter 0.5-4 cm on the posterolateral pleura bilaterally. FNAB of one lesion CT guided was not diagnostic. The pleural biopsy obtained at surgical exploration showed hyaline tissue, avascular, almost acellular, with calcifications and inflammation of low grade. The pleural plaques are generally multifocal and bilateral. They usually affect the parietal pleura. The connection between asbestos and plaques is firmly established. The pathogenesis is not well known. The pleural plaques fibrosis is a benign disease and a very common manifestation of asbestos exposure; it is not related to mesothelioma and it does not need any treatment. Because of the lack of symptoms it must be searched for in high risk subjects.}, } @article {pmid10414144, year = {1999}, author = {von Bültzingslöwen, F and Siemon, G}, title = {[Therapy of malignant pleural mesothelioma--a permanent dilemma].}, journal = {Pneumologie (Stuttgart, Germany)}, volume = {53}, number = {5}, pages = {266-275}, pmid = {10414144}, issn = {0934-8387}, mesh = {Mesothelioma/*therapy ; Pleural Neoplasms/*therapy ; }, abstract = {Although still a rare tumour, incidence of malignant pleural mesothelioma (MPM) is increasing. The cause, with the exception of some not clearly identified environmental factors, is asbestos. The prognosis is influenced by the stage of the disease. A new staging system has not modified the fact that staging is still a clinical problem. Tumour volume, histological subtype, sex and performance score are some of the important prognostic factors. Most patients (pts) are diagnosed in advanced stages only. Surgery will only cure or significantly prolong survival in the rare event of an early stage with no survival advantage for pleuropneumonectomy over pleurectomy. In early stages adjuvant immunological treatments (e.g. interferon or interleukin) may be of some value. Adjuvant first generation photodynamic therapy is not superior to operation only. The majority of patients, however, are diagnosed in advanced stages, where neither radiation nor chemotherapy, nor multimodality treatments can significantly alter the poor prognosis. There is no standard therapy, and no advantage to poly- versus monochemotherapy. Chemotherapy, however, seems to have some palliative effect in symptomatic patients, as well as radiotherapy, the latter also as prophylaxis against tumour invasion after puncture and thoracoscopy.}, } @article {pmid10412176, year = {1999}, author = {Neumann, V and Müller, KM and Fischer, M}, title = {[Peritoneal mesothelioma--incidence and etiology].}, journal = {Der Pathologe}, volume = {20}, number = {3}, pages = {169-176}, doi = {10.1007/s002920050340}, pmid = {10412176}, issn = {0172-8113}, mesh = {Asbestos/adverse effects ; Female ; Germany/epidemiology ; Humans ; Incidence ; Male ; Mesothelioma/*epidemiology/*etiology/pathology ; Middle Aged ; Peritoneal Neoplasms/*epidemiology/*etiology/pathology ; Pulmonary Fibrosis/complications/etiology ; Registries ; Sex Factors ; }, abstract = {A total of 70 malignant and 4 benign peritoneal mesotheliomas were diagnosed by the German Mesothelioma Registry between 1992 and 1998. Malignant mesotheliomas developed mainly in men (55/70); only one man had a benign peritoneal alteration. Age at first diagnosis of malignant mesotheliomas is about 59 years; the women are on average 4 years younger than the men. Mean survival time ranges about 1 year; in 6 of 38 patients longer survival times of up to 7 years are known. The epitheloid subtype predominates, but no effect on survival time is noticed. The percentage of patients with combined asbestos-associated lung fibrosis is higher than that for pleural mesotheliomas; these patients become ill about 6.5 years earlier. The latency period is 36 years on average. For most patients asbestos exposure is related to their occupation mainly in metal industries, asbestos industries, and in the building trade. There is no evidence for an induction of benign peritoneal alterations by asbestos dust.}, } @article {pmid10407698, year = {1999}, author = {Astoul, P}, title = {Pleural mesothelioma.}, journal = {Current opinion in pulmonary medicine}, volume = {5}, number = {4}, pages = {259-268}, doi = {10.1097/00063198-199907000-00015}, pmid = {10407698}, issn = {1070-5287}, mesh = {Combined Modality Therapy ; Female ; France/epidemiology ; Humans ; Incidence ; Male ; Mesothelioma/*diagnosis/epidemiology/*therapy ; Pleural Neoplasms/*diagnosis/epidemiology/*therapy ; Prognosis ; Risk Factors ; Survival Rate ; }, abstract = {The increasing incidence of malignant pleural mesothelioma (MPM), better knowledge of its pathogenesis with a strong implication of asbestos fibers, and some promising therapeutic results have led to a new interest in the management of patients with this disease. The diagnosis of MPM is easier because of new immunohistochemical markers that recognize the mesothelial cells with good specificity and sensitivity on pleural biopsy samples ideally obtained by thoracoscopy. Moreover, this endoscopic procedure allows the physician to make the diagnosis of MPM at an early stage, which is the key of the therapeutic management of this disease. If radiotherapy is necessary in preventing the malignant seeding after pleural procedures in patients, the lack of comparative studies did not show the superiority of a given treatment against another. A new international staging of the disease, however, allows physicians to discriminate several groups of patients for such comparative studies--in particular, for testing the efficacy of intrapleural therapy, e.g., cytokines--for early-stage MPM and multimodal management, i.e., extrapleural pneumonectomy, radiotherapy, and chemotherapy for more advanced diseases, has led to prolonged survival in carefully selected patients. To reach this target, all patients must be enrolled in protocols. The usual pessimism for the management of patients with malignant pleural mesothelioma is over.}, } @article {pmid10403693, year = {1999}, author = {Andersen, MK and Krarup-Hansen, A and Mårtensson, G and Winther-Nielsen, H and Thylen, A and Damgaard, K and Olling, S and Wallin, J}, title = {Ifosfamide in malignant mesothelioma: a phase II study.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {24}, number = {1}, pages = {39-43}, doi = {10.1016/s0169-5002(99)00030-6}, pmid = {10403693}, issn = {0169-5002}, mesh = {Adult ; Aged ; Antineoplastic Agents, Alkylating/adverse effects/*therapeutic use ; Humans ; Ifosfamide/adverse effects/*therapeutic use ; Male ; Mesothelioma/*drug therapy/mortality ; Middle Aged ; Pleural Neoplasms/*drug therapy/mortality ; Survival Rate ; }, abstract = {Malignant mesothelioma is a rare malignancy with a median survival, ranging from 4 to 18 months in untreated patients. In a phase II study of patients with mesothelioma, the efficacy and toxicity of ifosfamide and mesna was evaluated. Twenty-nine previously untreated patients, with histologically proven and unresectable mesothelioma, entered the study. Three patients were later excluded from the study due to revision of the diagnoses. The patients had to have bidimensionally measurable disease by CT scans and a WHO performance status < or = 3. Eligible patients received ifosfamide 3000 mg/m2 per day for 3 days as a 1-h infusion and mesna 1800 mg/m2 per day for 3 days every third week. Dose modifications were made according to the degree of hematologic, neurologic and renal toxicity. Response to treatment was evaluated in accordance with WHO criteria. The median age of patients was 59 years (range 39-68), 18 patients (69%) had a history of asbestos exposure and the median of treatment cycles was four (range 1-10). No complete responses were observed. One patient obtained a partial response after five cycles with a duration of response of 25 months. Nine patients (35%) had stable disease, while 13 (54%) progressed. The median survival for all patients was 10 months. The toxicity of the treatment was considerable. Thirteen patients (50%) had grade 4 leucopenia, ten patients (38%) had grade 3 or 4 reversible neurotoxicity and ten patients (38%) had grade 3 or 4 nausea and vomiting. Eleven patients (42%) went off the study due to the toxicity of the treatment. In conclusion, ifosfamide did not show any substantial activity of relevance in malignant mesothelioma at the dose level investigated, in spite of considerable toxicity.}, } @article {pmid10399473, year = {1999}, author = {de Pangher Manzini, V}, title = {[Chronic pleuropathy due to asbestos and malignant mesothelioma of the pleura: a differential diagnosis not always easy. A case report].}, journal = {Recenti progressi in medicina}, volume = {90}, number = {6}, pages = {331-333}, pmid = {10399473}, issn = {0034-1193}, mesh = {Asbestosis/complications/*diagnosis/pathology ; Chronic Disease ; Diagnosis, Differential ; Fatal Outcome ; Humans ; Male ; Mesothelioma/*diagnosis ; Middle Aged ; Pleura/pathology ; Pleural Effusion/diagnosis/pathology ; Pleural Neoplasms/*diagnosis ; Pleurisy/*diagnosis/etiology/pathology ; }, abstract = {A case of long-lasting chronic asbestos pleuritis is described. Radiological picture was initially that of an exudative pleuritis and subsequently that of pleural thickening associated to chronic pleural effusion. Cytological findings were suggestive for malignant pleural mesothelioma. Diagnosis was made only at autopsy. In absence of a sure histological diagnosis, the differential diagnosis of the two diseases (chronic asbestos pleuritis and malignant pleural mesothelioma) is not easy, so that necropsy retains a fundamental role in patients without a certain diagnosis in vita.}, } @article {pmid10398941, year = {1999}, author = {Finkelstein, MM}, title = {Maintenance work and asbestos-related cancers in the refinery and petrochemical sector.}, journal = {American journal of industrial medicine}, volume = {36}, number = {2}, pages = {326}, doi = {10.1002/(sici)1097-0274(199908)36:2<326::aid-ajim12>3.0.co;2-q}, pmid = {10398941}, issn = {0271-3586}, mesh = {Asbestos/*adverse effects ; Chi-Square Distribution ; Cohort Studies ; *Extraction and Processing Industry ; Humans ; Lung Neoplasms/*etiology ; *Maintenance ; Mesothelioma/etiology ; *Petroleum ; Risk Factors ; Time Factors ; }, } @article {pmid10395286, year = {1999}, author = {Carbone, M and Fisher, S and Powers, A and Pass, HI and Rizzo, P}, title = {New molecular and epidemiological issues in mesothelioma: role of SV40.}, journal = {Journal of cellular physiology}, volume = {180}, number = {2}, pages = {167-172}, doi = {10.1002/(SICI)1097-4652(199908)180:2<167::AID-JCP4>3.0.CO;2-Q}, pmid = {10395286}, issn = {0021-9541}, support = {R29 CA77220-01/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Cricetinae ; Gene Expression Regulation, Neoplastic ; Gene Expression Regulation, Viral ; Humans ; Mesothelioma/*epidemiology/genetics/virology ; Papillomavirus Infections/epidemiology/*genetics ; Pleural Neoplasms/*epidemiology/genetics/virology ; *Simian virus 40 ; Tumor Virus Infections/epidemiology/*genetics ; }, abstract = {Mesotheliomas are malignant tumors usually associated with occupational asbestos exposure. Simian virus 40 (SV40) is a DNA tumor virus that preferentially causes mesotheliomas when injected intracardially and/or intrapleurally into hamsters. SV40 also transforms human cells in tissue culture, and these cells contain extensive DNA damage. In the United States, at least 60% of human mesotheliomas contain and express SV40. In these tumor cells, the SV40 tumor antigen binds and inhibits the cellular tumor suppressors p53 and Rb. These findings suggest that SV40 may contribute to the development of those human mesotheliomas that occur in people not exposed to asbestos. SV40 may also facilitate asbestos-mediated carcinogenicity. The epidemiological data available are insufficient to address the role that SV40 may have played in contributing to the increased incidence of mesothelioma in the second half of this century.}, } @article {pmid10395284, year = {1999}, author = {Murthy, SS and Testa, JR}, title = {Asbestos, chromosomal deletions, and tumor suppressor gene alterations in human malignant mesothelioma.}, journal = {Journal of cellular physiology}, volume = {180}, number = {2}, pages = {150-157}, doi = {10.1002/(SICI)1097-4652(199908)180:2<150::AID-JCP2>3.0.CO;2-H}, pmid = {10395284}, issn = {0021-9541}, support = {CA-06927/CA/NCI NIH HHS/United States ; CA-45745/CA/NCI NIH HHS/United States ; }, mesh = {Asbestos/*adverse effects ; Carcinogens/*adverse effects ; Chromosome Aberrations/*chemically induced ; Chromosome Disorders ; Cyclin-Dependent Kinase Inhibitor p16/genetics ; Gene Deletion ; Genes, Tumor Suppressor/*drug effects ; Humans ; Mesothelioma/*chemically induced/genetics ; Pleural Neoplasms/*chemically induced/genetics ; }, abstract = {Exposure to the carcinogen asbestos is considered to be a major factor contributing to the development of most malignant mesotheliomas (MMs). We highlight the role of asbestos in MM and summarize cytogenetic and molecular genetic findings in this malignancy. The accumulation of numerous clonal chromosomal deletions in most MMs suggests a multistep process of tumorigenesis, characterized by the loss and/or inactivation of multiple tumor suppressor genes (TSGs). Cytogenetic and loss of heterozygosity (LOH) analyses of MMs have demonstrated frequent deletions of specific sites within chromosome arms 1p, 3p, 6q, 9p, 13q, 15q, and 22q. Furthermore, TSGs within two of these regions, i.e., p16/CDKN2A-p14ARF at 9p21 and NF2 at 22q12, are frequently altered in MMs. Homozygous deletion appears to be the major mechanism affecting p16/CDKN2A-p14ARF, whereas inactivating mutations coupled with allelic loss occur at the NF2 locus. Finally, recent studies have demonstrated the presence and expression of simian virus 40 (SV40) in many MMs. SV40 large T antigen has been shown to inactivate the TSG products Rb and p53, suggesting the possibility that asbestos and SV40 could act as cocarcinogens in MM. The frequent occurrence of homozygous deletions of p16/CDKN2A-p14ARF and the ability of SV40 Tag to bind TSG products suggest that perturbations of both Rb- and p53-dependent growth-regulatory pathways are critically involved in the pathogenesis of MM.}, } @article {pmid10380162, year = {1999}, author = {Berry, G}, title = {Models for mesothelioma incidence following exposure to fibers in terms of timing and duration of exposure and the biopersistence of the fibers.}, journal = {Inhalation toxicology}, volume = {11}, number = {2}, pages = {111-130}, doi = {10.1080/089583799197203}, pmid = {10380162}, issn = {0895-8378}, mesh = {Algorithms ; Animals ; Epidemiologic Methods ; Half-Life ; Humans ; Inhalation Exposure/*adverse effects ; Lung Neoplasms/*epidemiology/etiology ; Mesothelioma/*epidemiology/etiology ; Mineral Fibers/*toxicity ; Models, Statistical ; Rats ; }, abstract = {The health effects of inhaled fibers are related to the intensity and duration of exposure and occur many years after the exposure. In particular, the incidence of mesothelioma after exposure to asbestos is proportional to the intensity of exposure (fibers per milliliter of air) and the duration of exposure, and to the time that has elapsed since the exposure. The incidence increases with time since exposure to a power of between 3 and 4. The disease process resulting from exposure to fibers in the air is presumably related to the dose of fibers in the lungs, which depends on the exposure level and duration, and also on the size characteristics of the fibers influencing their inhalation and retention in the lungs. Models incorporating these characteristics have been found to be satisfactory in explaining the incidence of mesothelioma over time after exposure to asbestos. Most of the epidemiological modeling has been for occupational exposure to one of the amphibole asbestos types (crocidolite or amosite), for which heavy exposure produces a high incidence of mesothelioma. Occupational exposure to chrysotile asbestos has resulted in a much lower incidence of mesothelioma. Crocidolite asbestos is much more biopersistent than chrysotile asbestos in the sense that after retention in the lungs it is eliminated only slowly (half-time of several years). If fibers are eliminated then the dose in the lungs declines following exposure, and this may influence the disease process. This concept is more important for synthetic mineral fibers, such as glass wool, which are used as a substitute for asbestos. These fibers are much less biopersistent than asbestos, with half-times of weeks or even days. Biopersistence is related to the dissolution of fibers. This is a physical-chemical process that may be expected to proceed at about the same rate in rats and humans. The predicted effect of biopersistence of fibers has been explored using the basic mesothelioma incidence model generalized to include a term representing exponential elimination over time. The influence of solubility of fibers on the mesothelioma rate is 17 times higher in humans than in rats. This is because rats are aging and developing cancer at a much quicker rate than humans, and hence the influence of dissolution is less. Thus, the predicted mesothelioma incidence in humans is highly dependent on the rate of elimination across the range covering asbestos and the more durable synthetic fibers, but in rats a similar dependence occurs at a 17 times higher rate of elimination corresponding to the less durable synthetic fibers. The possible carcinogenic effects of fibers are often determined from animal experiments, but these results suggest that the extrapolation from rats to humans is highly dependent on the biopersistence of fibers, in the situation where the elimination is through dissolution of fibers at a rate independent of species and the speed of the cancer process is species dependent. This implies that relatively soluble fibers that do not produce disease in rat experiments are even less likely to produce disease in humans.}, } @article {pmid10372416, year = {1999}, author = {Rosenthal, GJ and Simeonova, P and Corsini, E}, title = {Asbestos toxicity: an immunologic perspective.}, journal = {Reviews on environmental health}, volume = {14}, number = {1}, pages = {11-20}, doi = {10.1515/reveh.1999.14.1.11}, pmid = {10372416}, issn = {0048-7554}, mesh = {Antibody Formation ; Asbestos/*adverse effects/chemistry ; Asbestosis/*immunology ; B-Lymphocytes/drug effects/immunology ; Humans ; Immune System/*drug effects ; Killer Cells, Natural/drug effects/immunology ; Macrophages/drug effects/immunology ; Occupational Exposure/adverse effects ; T-Lymphocytes/drug effects/immunology ; }, abstract = {Asbestos has long been associated with a number of life threatening pulmonary diseases, including asbestosis and mesothelioma. While the lung is the primary target organ for asbestos toxicity, a number of clinical and experimental studies over the past 30 years have shown that the immune system may also be altered by exposure to asbestos at occupationally relevant concentrations. Whereas early clinical studies generally focused on systemic observations of immune alteration, more recent studies have assessed the immunological changes occurring in the lung, the primary target organ of asbestos. This review will focus on the investigations that examine the influence of asbestos on systemic and local immunity, as well as the role that the immune system may play in asbestos-related disease.}, } @article {pmid10366897, year = {1999}, author = {Miller, BG and Searl, A and Davis, JM and Donaldson, K and Cullen, RT and Bolton, RE and Buchanan, D and Soutar, CA}, title = {Influence of fibre length, dissolution and biopersistence on the production of mesothelioma in the rat peritoneal cavity.}, journal = {The Annals of occupational hygiene}, volume = {43}, number = {3}, pages = {155-166}, pmid = {10366897}, issn = {0003-4878}, mesh = {Animals ; Asbestos, Amosite/*adverse effects/analysis ; Biodegradation, Environmental ; Carbon Compounds, Inorganic/*adverse effects/analysis ; Carcinogenicity Tests ; *Disease Models, Animal ; Dose-Response Relationship, Drug ; *Glass/analysis ; Male ; Mesothelioma/*etiology/mortality/pathology ; Mineral Fibers/*adverse effects/analysis ; Neoplasms, Experimental/*etiology/mortality/pathology ; Peritoneal Neoplasms/*etiology/mortality/pathology ; Rats ; Rats, Wistar ; Silicon Compounds/*adverse effects/analysis ; Survival Analysis ; Time Factors ; }, abstract = {A range of respirable man-made mineral fibres were tested for evidence of carcinogenicity by injection into the peritoneal cavity of male SPF Wistar rats; and differences in carcinogenicity were related to the dimensions and biopersistence of the injected fibres. The fibres tested included an amosite asbestos, a silicon carbide whisker, a special purpose glass microfibre, and a range of other man-made vitreous fibres (MMVFs) and refractory ceramic fibres (RCFs) from the TIMA fibre repository. The injected dose of each was designed as the estimated mass required to contain 10(9) fibres > 5 microns in length, as determined by optical microscopy. The numbers of long fibres (> 15 microns) contained in these doses ranged across fibres from 0.1 x 10(9) to 0.8 x 10(9) fibres; the number of long fibres thinner than 0.95 micron ranged from 0.015 x 10(9) to 0.4 x 10(9). The treatment groups contained between 18 and 24 animals. Animals were killed when they showed signs of debilitation. At autopsy, the diagnosis of mesothelioma was usually obvious macroscopically. Otherwise, histological examination of peritoneal organs was used to search for early tumour development. Judged by median survival time, four of the fibre types, in the doses administered, presented higher mesothelioma activity than amosite asbestos. The other fibres tested were less carcinogenic than the amosite. Only a ceramic material derived by extreme heating to simulate the effect of furnace or oven conditions, produced no mesotheliomas. Attempts were made, using regression models, to relate these differences to fibre dimensions and to measures of durability from separate experiments. The results pointed principally to a link with the injected numbers of fibres > 20 microns in length and with biopersistence in the rat lung of fibres longer than 5 microns. Improved quantification of the relative importance of fibre dimensions and biopersistence indices requires experimentation with a range of doses.}, } @article {pmid10361603, year = {1999}, author = {Bulbulyan, MA and Ilychova, SA and Zahm, SH and Astashevsky, SV and Zaridze, DG}, title = {Cancer mortality among women in the Russian printing industry.}, journal = {American journal of industrial medicine}, volume = {36}, number = {1}, pages = {166-171}, doi = {10.1002/(sici)1097-0274(199907)36:1<166::aid-ajim24>3.0.co;2-p}, pmid = {10361603}, issn = {0271-3586}, mesh = {Adult ; Aged ; Cohort Effect ; Cohort Studies ; Confidence Intervals ; Female ; Humans ; Middle Aged ; Moscow/epidemiology ; Neoplasms/etiology/*mortality ; Occupational Diseases/*mortality ; Occupational Exposure/adverse effects/*statistics & numerical data ; Occupations/statistics & numerical data ; Odds Ratio ; Poisson Distribution ; Printing/*statistics & numerical data/trends ; Retrospective Studies ; Women's Health ; }, abstract = {BACKGROUND: This study evaluates cancer mortality among women employed in two large printing plants in Moscow.

METHODS: A total of 3,473 women who were actively employed as of December 31, 1978, with a minimum of 2 years employment were followed from 1 January 1979 to 31 December 1993. There were 47,791 person-years observed, with only 51 women lost to follow-up (1.5%). Standardized mortality ratios (SMRs) were calculated using the population of Moscow to generate expected numbers. Analyses by job (compositors, press operators, and bookbinders), age hired, latency, and duration of employment were conducted.

RESULTS: Among women employed in the two printing plants, there was a significant excess of esophageal cancer, based on seven deaths (expected = 2.7, SMR = 2.7, 95% CI = 1.1-5.4). Four of the seven esophageal cancer deaths occurred among bookbinders (expected = 1.0, SMR = 4.1, 95% CI = 1.1-10.4), all among workers hired before 1957 (expected = 0.6, SMR = 7.1, 95% CI = 1.9-18.3), the last year benzene was used in bookbinding. Ovarian cancer was also significantly elevated among bookbinders (12 observed, 4.2 expected, SMR = 2.9, 95% CI = 1.5-5.0), which, along with one death from mesothelioma of the abdomen, might be related to the use of asbestos-contaminated talc fillers in paper. Press operators had significantly elevated mortality from stomach cancer (observed = 9, expected = 4.1, SMR = 2.2, 95% CI = 1.0-4.2) and, based on two deaths each, melanoma and bladder cancer.

CONCLUSIONS: Women in this printing industry cohort experienced excess mortality of cancer of the esophagus and stomach, with suggested increases of melanoma and bladder cancer. Further follow-up of this cohort, which would allow more in-depth analysis of rare cancer sites, latency, and duration of employment, is warranted. Gender comparisons within the cohort should also be conducted to clarify the role of occupational and lifestyle factors in the etiology of cancer among workers in the printing industry.}, } @article {pmid10361597, year = {1999}, author = {Germani, D and Belli, S and Bruno, C and Grignoli, M and Nesti, M and Pirastu, R and Comba, P}, title = {Cohort mortality study of women compensated for asbestosis in Italy.}, journal = {American journal of industrial medicine}, volume = {36}, number = {1}, pages = {129-134}, doi = {10.1002/(sici)1097-0274(199907)36:1<129::aid-ajim18>3.0.co;2-9}, pmid = {10361597}, issn = {0271-3586}, mesh = {Adult ; Aged ; Asbestosis/*mortality ; Cause of Death ; Cohort Studies ; Confidence Intervals ; Construction Materials ; Female ; Humans ; Italy/epidemiology ; Middle Aged ; Neoplasms/etiology/mortality ; Odds Ratio ; Respiratory Tract Diseases/etiology/mortality ; Textile Industry/statistics & numerical data ; Women's Health ; Workers' Compensation/*statistics & numerical data ; }, abstract = {BACKGROUND: The carcinogenic effect of asbestos is accepted for lung cancer and mesothelioma, while conflicting opinions exist for other cancer sites. The aim of the present investigation is to study cause-specific mortality of women compensated for asbestosis who had certainly been exposed to high levels of asbestos fibers.

METHODS: The cause-specific mortality of all Italian women compensated for asbestosis and alive December 31, 1979, was investigated through October 30, 1997. In the total cohort, which included 631 subjects, 277 deaths occurred. Cause-specific SMRs (Standardized Mortality Ratio) were computed using the national rates for comparison.

RESULTS: A significantly increased mortality for all diseases related to asbestos exposure was observed. Mortality for all causes, all neoplasms, lung cancer, uterine cancer, ovarian cancer, and non-neoplastic respiratory diseases was significantly increased. Separate analyses for textile (n = 276) and asbestos-cement (n = 278) workers were performed. Women employed in the textile industry, mainly exposed to chrysotile, who are compensated at a younger age, showed higher SMRs for lung cancer and asbestosis. Women in the asbestos-cement industry, mainly exposed to crocidolite containing asbestos mixtures, experienced higher mortality for pleural malignancies.

CONCLUSIONS: The role of asbestos exposure in the development of gastrointestinal and genital neoplasms is discussed.}, } @article {pmid10359850, year = {1999}, author = {Shah, IA and Salvatore, JR and Kummet, T and Gani, OS and Wheeler, LA}, title = {Pseudomesotheliomatous carcinoma involving pleura and peritoneum: A clinicopathologic and immunohistochemical study of three cases.}, journal = {Annals of diagnostic pathology}, volume = {3}, number = {3}, pages = {148-159}, doi = {10.1016/s1092-9134(99)80042-2}, pmid = {10359850}, issn = {1092-9134}, mesh = {Aged ; Antigens, Neoplasm/analysis ; Antigens, Surface/analysis ; Biomarkers, Tumor/analysis ; Carcinoma/chemistry/*pathology ; Glycoproteins/analysis ; Humans ; Immunohistochemistry ; Male ; Mesothelioma/chemistry/*pathology ; Middle Aged ; Peritoneal Neoplasms/chemistry/*pathology ; Pleural Neoplasms/chemistry/*pathology ; }, abstract = {Pseudomesotheliomatous carcinoma is a rare variant of peripheral adenocarcinoma of the lung that can manifest clinical, radiologic, and pathologic features similar to malignant mesothelioma. We present three patients with pseudomesotheliomatous carcinoma of the lung. In one patient the carcinoma extended beyond the thorax and extensively involved the peritoneum, mesentery, omentum, and intestines. All patients experienced weight loss and chest pain. All were white men aged 63, 65, and 67 years. Two were smokers and had shortness of breath, cough, and pleural effusion. One had a history of asbestos exposure. No patient developed dyspnea or hemoptysis. One was successfully treated for prostatic carcinoma 18 months earlier. Radiographically, all tumors were pleura-based. Grossly, the tumors spread extensively over pleural (and in one case peritoneal) surfaces and mimicked malignant mesothelioma. Histologically, all tumors were poorly differentiated and necrotic; two tumors exhibited spindle-cell components and desmoplasia. Mucin production was detectable in none, 10%, and 50% of tumor cells. The percentages of tumor cells immunoreactive for Ber-EP4 were 70%, 100%, and 80%; for Leu MI 0%, 90%, and 50%; for epithelial membrane antigen 80%, 80%, and 100%; for B 72.3%, 0%, 90%, and 20%; for polyclonal carcinoembryonic antigen 0%, 10%, and 10%; and for monoclonal 5%, 0%, and 0%. Of these, Ber-EP4 and B 72.3 rendered the most reliable diagnostic results. The clinical, radiologic, and gross and routine histologic findings were similar to those of a malignant mesothelioma; the final diagnosis could be made based mainly on immunocytochemical results. We have reviewed the English and German literature regarding 65 such tumors and present our experience with three additional cases. We emphasize the application of immunocytochemical studies on pleura-based poorly or undifferentiated malignant tumors of unknown origin.}, } @article {pmid10350513, year = {1999}, author = {Albin, M and Magnani, C and Krstev, S and Rapiti, E and Shefer, I}, title = {Asbestos and cancer: An overview of current trends in Europe.}, journal = {Environmental health perspectives}, volume = {107 Suppl 2}, number = {Suppl 2}, pages = {289-298}, pmid = {10350513}, issn = {0091-6765}, mesh = {Asbestos/*adverse effects/analysis ; Carcinogens/*adverse effects/analysis ; Environmental Monitoring ; Epidemiological Monitoring ; Europe/epidemiology ; Female ; Humans ; Incidence ; Lung Neoplasms/*epidemiology/*etiology ; Male ; Mesothelioma/*epidemiology/*etiology ; Occupational Diseases/*epidemiology/*etiology ; Population Surveillance ; Risk Factors ; Sex Distribution ; Smoking/adverse effects ; }, abstract = {This review assesses the contribution of occupational asbestos exposure to the occurrence of mesothelioma and lung cancer in Europe. Available information on national asbestos consumption, proportions of the population exposed, and exposure levels is summarized. Population-based studies from various European regions on occupational asbestos exposure, mesothelioma, and lung cancer are reviewed. Asbestos consumption in 1994 ranged, per capita, between 0. 004 kg in northern Europe and 2.4 kg in the former Soviet Union. Population surveys from northern Europe indicate that 15 to 30% of the male (and a few percent of the female) population has ever had occupational exposure to asbestos, mainly in construction (75% in Finland) or in shipyards. Studies on mesothelioma combining occupational history with biologic exposure indices indicate occupational asbestos exposure in 62 to 85% of the cases. Population attributable risks for lung cancer among males range between 2 and 50% for definite asbestos exposure. After exclusion of the most extreme values because of methodologic aspects, most of the remaining estimates are within the range of 10 to 20%. Estimates of women are lower. Extrapolation of the results to national figures would decrease the estimates. Norwegian estimates indicate that one-third of expected asbestos-related lung cancers might be avoided if former asbestos workers quit smoking. The combination of a current high asbestos consumption per capita, high exposure levels, and high underlying lung cancer rates in Central Europe and the former Soviet Union suggests that the lung cancers will arise from the smoking-asbestos interaction should be a major concern.}, } @article {pmid10350509, year = {1999}, author = {Merler, E and Vineis, P and Alhaique, D and Miligi, L}, title = {Occupational cancer in Italy.}, journal = {Environmental health perspectives}, volume = {107 Suppl 2}, number = {Suppl 2}, pages = {259-271}, pmid = {10350509}, issn = {0091-6765}, mesh = {Carcinogens/adverse effects/analysis ; Epidemiologic Research Design ; Female ; Humans ; Incidence ; Industry ; Italy/epidemiology ; Male ; Neoplasms/economics/*epidemiology/etiology/*prevention & control ; Occupational Diseases/economics/*epidemiology/etiology/*prevention & control ; Occupational Exposure/adverse effects/analysis ; Occupational Health/legislation & jurisprudence ; Population Surveillance ; Registries ; Risk Factors ; Workers' Compensation/organization & administration ; }, abstract = {This article is a discussion of occupational cancer in Italy. The introduction provides the necessary context of Italian industrialization and occupational health regulation. This is followed by a review of Italian epidemiologic studies of occupational cancer risks considered in terms of relative measures of risk and attributable risk of carcinogenic agents or exposure circumstances. We attempt to establish the number of workers exposed to carcinogens in Italy and the intensity of their exposures. Finally, the Italian system of compensation for occupational cancer is discussed. Several cohort and case-control studies have addressed the issue of occupational risks, mostly among male workers. The results of these studies suggest that the growing incidence of and mortality by mesothelioma is explained by the widespread and intense exposure to asbestos in some Italian industrial settings. A high attributable risk of lung tumors among male populations in industrial areas of northern Italy is explained by occupational exposures. However, insufficient data are available for clear definition of the extent and intensity of occupational exposure to carcinogenic substances. In Italy, we must prioritize and maximize resources in occupational cancer epidemiology and revitalize the role of national institutions. Recent legislation has established new regulations on the handling of carcinogenic substances in industrial settings, a new list of occupational diseases, and a national registry of mesothelioma linked to asbestos exposure. These legislative changes are expected to have positive effects.}, } @article {pmid10350508, year = {1999}, author = {Brüske-Hohlfeld, I}, title = {Occupational cancer in Germany.}, journal = {Environmental health perspectives}, volume = {107 Suppl 2}, number = {Suppl 2}, pages = {253-258}, pmid = {10350508}, issn = {0091-6765}, mesh = {Asbestos/adverse effects/analysis ; Carcinogens/adverse effects/analysis ; Germany/epidemiology ; Humans ; Incidence ; Neoplasms/economics/*epidemiology/etiology/*prevention & control ; Occupational Diseases/economics/*epidemiology/etiology/*prevention & control ; Occupational Exposure/adverse effects/analysis ; Population Surveillance ; Radiation, Ionizing ; Risk Factors ; Workers' Compensation/organization & administration ; }, abstract = {As in probably mostly all other European countries, the incidence of occupational cancer in Germany increased steadily after World War II. In 1994 about 1,600 cases of occupational cancer were compensated--more than ever before. More than half of these cases were lung cancer, most caused either by asbestos (n=545) or by ionizing radiation ((italic)n(/italic)=306). Other frequent target organs of asbestos were the pleura and the peritoneum with 495 cases of mesotheliomas. Asbestos was the single most important risk factor for occupational cancer, causing more than 1000 deaths per year. All other malignant diseases, such as bladder cancer, leukemia, angiosarcoma of the liver, adenocarcinoma of the nose or nasal sinuses, and skin cancer, were comparatively rare. Although primary exposure to ionizing radiation in uranium ore mining occurred in the 1950s and attributable lung cancers seem to be on the decline, this is not true for asbestos, where the peak incidence in lung cancer and mesothelioma has not been reached yet.}, } @article {pmid10350506, year = {1999}, author = {Coggon, D}, title = {Occupational cancer in the United Kingdom.}, journal = {Environmental health perspectives}, volume = {107 Suppl 2}, number = {Suppl 2}, pages = {239-244}, pmid = {10350506}, issn = {0091-6765}, mesh = {Adult ; Aged ; Carcinogens/adverse effects/analysis ; Female ; Humans ; Male ; Middle Aged ; Neoplasms/*epidemiology/etiology/prevention & control ; Occupational Diseases/*epidemiology/etiology/prevention & control ; Occupational Exposure/adverse effects/analysis ; Occupational Health/legislation & jurisprudence ; Population Surveillance ; Risk Factors ; United Kingdom/epidemiology ; }, abstract = {Most of the known occupational hazards of cancer have occurred in the United Kingdom. Over recent decades a contraction of manufacturing industry and legal controls on carcinogens have led to reductions in exposure, but cases continue to occur, often as a consequence of exposures 20 or more years ago. By far the most important occupational cause of cancer in the United Kingdom is asbestos, which currently accounts for some 600 cases of mesothelioma and perhaps 100 cases of bronchial carcinoma per year. Recent trends suggest that the number of mesothelioma cases attributable to asbestos will increase over the next few decades. Exposure to sunlight in outdoor work may cause several hundred cases of nonmelanomatous skin cancer per year, and occupational exposure to polycyclic aromatic hydrocarbons could be responsible for a similar number of skin and lung tumors. Other known occupational hazards of cancer are unlikely to account for more than 100 cases per year in total.}, } @article {pmid10347962, year = {1998}, author = {Mercurio, S and Poleri, C and Carassai, M and Abdala, O and Lombardi, D and Levy, R and Rojas, O and Morero, J and Rosenberg, M}, title = {[Malignant pleural mesotheliomas].}, journal = {Medicina}, volume = {58}, number = {6}, pages = {699-706}, pmid = {10347962}, issn = {0025-7680}, mesh = {Adult ; Aged ; Antibodies, Monoclonal ; Female ; Humans ; Male ; *Mesothelioma/diagnosis/mortality/therapy ; Middle Aged ; *Pleural Neoplasms/diagnosis/mortality/therapy ; Prognosis ; Retrospective Studies ; }, abstract = {An increase in incidence of malignant pleural mesotheliomas has been noted recently. In order to assess our own experience, we reviewed all medical records and biopsies of patients who were seen with this diagnosis in Hospital Maria Ferrer between January 1986 and December 1997. Clinical data of 17 patients were analyzed. Mean age was 59 years, 76% were male. Industrial or environmental exposure to asbestos was established in 9 patients (53%). Most common symptoms at presentation were dyspnea (88%) and chest pain (65%). Pleural thickening with or without effusion was the usual finding in chest X rays and CAT scans. Biochemical analysis of pleural fluids was consistent with exudate. Diagnosis was performed by thoracotomy (47%), needle biopsy (23.5%) and videothoracoscopy (29.5%). Histological samples were available for review in 16 of the 17 patients: they were epithelial (10), sarcomatoid (2) and mixed tumors (4). Treatment reflected varying approaches. Palliative methods (pleurodesis, chemotherapy and radiotherapy) were preferred at the beginning while more aggressive interventions are performed nowadays. Pleuroneumonectomy alone or in combination with other therapies was carried out in 5 patients with no operative mortality although some complications occurred such as empyema, bronchopleural fistula and severe chest pain. Survival rate for all groups was 10.5 +/- 5.9 months. However, the mean survival of patients who underwent surgery was 17.5 +/- 2.1 months (p < 0.04) with an associated improvement in quality of life. Therefore, we consider that surgery associated with other therapies offers at present, the best therapeutic option for this bad prognosis condition.}, } @article {pmid10344157, year = {1999}, author = {Lalowicz, I}, title = {[Extrapleural mesothelioma].}, journal = {Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego}, volume = {6}, number = {31}, pages = {47-49}, pmid = {10344157}, issn = {1426-9686}, mesh = {Adult ; Asbestos/*adverse effects ; Female ; Heart Neoplasms/*etiology/therapy ; Humans ; Male ; Mesothelioma/*etiology/therapy ; Peritoneal Neoplasms/*etiology/therapy ; Vaginal Neoplasms/*etiology ; }, abstract = {Malignant mesothelioma of the peritoneum, pericardium and tunica vaginalis is a rare neoplasm usually associated with exposure to asbestos. The disease is most common in males over the age 40 years with sings and symptoms of neoplastic disease with or without a palpable abdominal mass, abdominal pain and ascites. Diagnosis is often possibly only after direct vision and histologic examination. Different types of peritoneal mesothelioma occur in adults and in children. Only small proportion of all patients with mesothelioma can be cured surgically. Both radiotherapy and standard chemotherapy have only limited usefulness. The optimal management malignant mesothelioma continues to be defined.}, } @article {pmid10341747, year = {1999}, author = {Howel, D and Gibbs, A and Arblaster, L and Swinburne, L and Schweiger, M and Renvoize, E and Hatton, P and Pooley, F}, title = {Mineral fibre analysis and routes of exposure to asbestos in the development of mesothelioma in an English region.}, journal = {Occupational and environmental medicine}, volume = {56}, number = {1}, pages = {51-58}, pmid = {10341747}, issn = {1351-0711}, mesh = {Aged ; Asbestos/*analysis ; Case-Control Studies ; Environmental Exposure ; Female ; Humans ; *Lung ; Lung Neoplasms/*etiology ; Male ; Mesothelioma/*etiology ; Middle Aged ; Occupational Diseases/*etiology ; Occupational Exposure ; }, abstract = {OBJECTIVES: To compare the concentrations of inorganic fibres in the lungs in cases of mesothelioma and controls: to determine whether concentrations of retained asbestos fibres differ with the different exposures identified from interview; and to investigate the existence of a cut off point in concentrations of asbestos fibres that indicates occupational exposure.

METHODS: Case-control study; 147 confirmed cases of mesothelioma and 122 controls identified from deaths occurring in four districts of Yorkshire between 1979 and 1991. Surviving relatives were interviewed to determine lifetime exposure history to asbestos. Mineral fibre analysis was carried out on lung tissue from postmortem examinations.

RESULTS: Odds on high concentrations of retained asbestos fibres were greater in cases than controls. After excluding subjects with occupational and paraoccupational exposure, the odds on high concentrations were still greater in cases than controls, but only significantly so for amphiboles. There was only a weak relation between probability of occupational exposure to asbestos and concentrations of retained asbestos fibres, and no significant difference in fibre concentrations was found between subjects who had been exposed to asbestos through different routes: these comparisons were only based on small groups. There was considerable overlap in concentrations of retained asbestos fibres between cases and controls with and without histories of occupational exposure.

CONCLUSIONS: The study has confirmed previous results of higher concentrations of asbestos fibres in cases than controls, and has shown that this is still found in subjects with little evidence of occupational and para-occupational exposure. The overlap in concentrations of retained asbestos for different groups of subjects did not suggest a clear cut of value.}, } @article {pmid10339953, year = {1999}, author = {Foà, V and Basilico, S}, title = {[Chemical and physical characteristics and toxicology of man-made mineral fibers].}, journal = {La Medicina del lavoro}, volume = {90}, number = {1}, pages = {10-52}, pmid = {10339953}, issn = {0025-7818}, mesh = {Animals ; Biodegradation, Environmental ; Carcinogenicity Tests ; Cell Line ; Ceramics/adverse effects ; Cricetinae ; Cricetulus ; Cytotoxicity Tests, Immunologic ; Female ; Humans ; Male ; Manufactured Materials ; Mesothelioma/*etiology ; Mice ; *Mineral Fibers/toxicity ; Mutagenicity Tests ; Occupational Diseases/*etiology ; *Occupational Exposure ; Peritoneal Neoplasms/etiology ; Pleural Neoplasms/*etiology ; Rats ; Risk Factors ; Time Factors ; }, abstract = {The evidence for the adverse health effects following exposure to asbestos (i.e. fibrogenic and carcinogenic effect) has prompted widespread removal of asbestos-containing materials and led to banning of asbestos internationally (in Italy, DPR 257/1992), resulting in the increased use of substitutes composed of both naturally occurring and synthetic materials, including man made mineral fibres (MMMFs) and man made organic fibres (MMOF). MMMFs represent a family of synthetic, inorganic vitreous substances derived primarily from glass, rock, slag, or clay. MMMFs are further divided into two categories: 1) man made vitreous fibres (MMVFs), further divided as follows: a) fibrous glass, including mainly continuous filament, special purpose fibres; and microfibres. The materials are typically composed of oxides of silicon, calcium, sodium, potassium, aluminum, and boron. b) Mineral wool, including glass wool, rock wool (derived from magma rock) and slag wool (made from molten slag produced in metallurgical processes such as the production of iron, steel, or copper). The main components of rock wool and slag wool are oxides of silicon, calcium, magnesium, aluminum, and iron. 2) Refractory/ceramic fibres, amorphous or partially crystalline materials made from kaolin clay or oxides of aluminum, silicon or other metal oxides (i.e. oxides of zirconium and yttrium). Less commonly, refractory fibres are also made from non-oxide refractory materials such as silicon carbide, silicon nitride, or boron nitride. Industrial production of MMVFs began in the second half of the 19th century, while ceramic fibres production began more recently, in the early 1970s. Major uses of MMMFs include thermal, acoustic and aerospace insulation, fire proofing, reinforcing material in plastics, cement and textile, optic fibres, air and liquid filtration, friction products, refractory coatings. Serious questions have been raised about health implications of MMMFs. Suspicion about the possible occurrence of adverse effects following exposure to MMMFs arises mainly from some similarities of MMMFs with asbestos (fibrous aspects, inhalability, chemical composition, free radical formation). The fibre characteristics that have been identified as crucial in influencing the pathogenesis of fibre-related adverse respiratory effects can be mainly divided into two groups: fibre dimension, and chemical composition and structure. Fibre dimension plays a determining role in conditioning penetration in the lung. In a broad sense, the term "respirable" means "capable of being carried by breath into the respiratory system". For regulatory purposes, "respirable fibres" (i.e. RFP) are defined in most countries following WHO criteria: length > 5 microns, diameter < 3 microns, length/diameter > 3. MMMFs are generally produced as fibres of diameter higher than asbestos, and too large in diameter to be respirable. Moreover, due to the production process, they are structurally amorphous. Since MMMFs have no crystalline domains, they also have no clearly defined structural faults and they fracture transversely, and randomly. Fragments that are too large to be taken up by macrophages can be resolved in the lung by a leaching--or dissolution--process which leads to a progressive reduction of particle length. In contrast, when abraded, asbestos tends to split longitudinally into new, fine, straight fibres: these fibrils are of much smaller diameter, more respirable, and consequently more hazardous than parent fibres. Fibre chemical composition plays a determining role in conditioning the higher or lower biological activity, durability, biopersistence, and biodegradability. The term "biological activity" means reactivity or ability to interact (possibly due to formation of active oxygen species, identified as a crucial step in the mechanism of action) with biological structures and tissues. Fibre "durability" is strictly related to its solubility. It can be defined as the ability to resist}, } @article {pmid10336997, year = {1999}, author = {Rödelsperger, K and Woitowitz, HJ and Brückel, B and Arhelger, R and Pohlabeln, H and Jöckel, KH}, title = {Dose-response relationship between amphibole fiber lung burden and mesothelioma.}, journal = {Cancer detection and prevention}, volume = {23}, number = {3}, pages = {183-193}, doi = {10.1046/j.1525-1500.1999.99018.x}, pmid = {10336997}, issn = {0361-090X}, mesh = {Age Factors ; Aged ; Asbestos, Amphibole/*adverse effects/analysis ; Asbestos, Serpentine/adverse effects/analysis ; Asbestosis/epidemiology/etiology ; Body Burden ; Carcinogens/*adverse effects ; Case-Control Studies ; Dose-Response Relationship, Drug ; Female ; Germany/epidemiology ; Humans ; Lung Neoplasms/*chemically induced/epidemiology ; Male ; Mesothelioma/*chemically induced/epidemiology ; Microscopy, Electron, Scanning Transmission ; Middle Aged ; Mineral Fibers/adverse effects/analysis ; Odds Ratio ; Sex Factors ; Smoking ; }, abstract = {In a mesothelioma case-control study, asbestos and other mineral fibers from lung burden were examined as causal factors. Diagnosis was confirmed by a panel of pathologists. For 66 cases and 66 controls from hospitals in five German towns, lung tissue fiber analysis by transmission electron microscopy was available. Control patients were treated by a surgical lung resection mostly because of lung cancer. For chrysotile and other mineral fibers a significantly increased odds ratio (OR) was not observed. A clear dose-response relationship was demonstrated for the concentration CA of amphibole fibers longer than 5 microm. Between 0.025 and 2.5 fibers/microg dry weight (f/microg) the relationship can be approximated as OR = CA/(0. 025 f/microg). Similar but less distinct dose-response relationships were found in a Canadian and an Australian study. It is concluded that among German mesothelioma patients factors not associated with amphibole fiber concentration are not predominating.}, } @article {pmid10334642, year = {1999}, author = {Karjalainen, A and Pukkala, E and Kauppinen, T and Partanen, T}, title = {Incidence of cancer among Finnish patients with asbestos-related pulmonary or pleural fibrosis.}, journal = {Cancer causes & control : CCC}, volume = {10}, number = {1}, pages = {51-57}, doi = {10.1023/a:1008845332422}, pmid = {10334642}, issn = {0957-5243}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Asbestosis/*complications ; Carcinogens/*adverse effects ; Cohort Studies ; Female ; Finland/epidemiology ; Humans ; Male ; Middle Aged ; *Occupational Exposure ; Pleura/pathology ; Prognosis ; Pulmonary Fibrosis/*complications ; }, abstract = {OBJECTIVES: To study the asbestos-associated risk of lung cancer according to the histological type of cancer, the time of and time since diagnosis of asbestosis, the asbestos-associated risk for cancers other than lung cancer or mesothelioma, and the predictive value of asbestos-related pleural abnormalities as regards the risk of cancer.

METHODS: Finnish patients with asbestosis (n = 1,376) or asbestos-related benign pleural disease (n = 4,887) notified as an occupational disease since 1964 were followed-up through the Finnish Cancer Registry for cancer in 1967-95.

RESULTS: Compared with the total cancer incidence in Finland, men with asbestosis had a raised risk of lung cancer (standardized incidence ratio [SIR] = 6.7; 95% confidence interval [CI] = 5.6-7.9), mesothelioma (SIR = 32, CI = 14-60) and cancer of the larynx (SIR = 4.2, CI = 1.4-9.8). The risk of lung cancer was similarly raised for all histological types of lung cancer (the highest in insulators) and did not change markedly over time of notification or duration of follow-up. Men with benign pleural disease had a raised risk of mesothelioma (SIR = 5.5, CI = 1.5-14) and a slightly elevated risk of lung cancer (SIR = 1.3, CI = 1.0-1.8). Among women with asbestosis, significant excess was found for lung cancer and mesothelioma.

CONCLUSION: Asbestosis and asbestos-related benign pleural disease seem to possess different predictive values as regards the risk of lung cancer.}, } @article {pmid10334193, year = {1999}, author = {Xu, L and Flynn, BJ and Ungar, S and Pass, HI and Linnainmaa, K and Mattson, K and Gerwin, BI}, title = {Asbestos induction of extended lifespan in normal human mesothelial cells: interindividual susceptibility and SV40 T antigen.}, journal = {Carcinogenesis}, volume = {20}, number = {5}, pages = {773-783}, doi = {10.1093/carcin/20.5.773}, pmid = {10334193}, issn = {0143-3334}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antigens, Polyomavirus Transforming/analysis ; Apoptosis/drug effects ; Asbestos/*adverse effects ; Asbestos, Amosite/adverse effects ; Carcinogens/*adverse effects ; Cell Division/drug effects ; Cell Line ; Cellular Senescence/*drug effects/genetics ; Cyclin-Dependent Kinase Inhibitor p16/genetics/metabolism ; Cyclin-Dependent Kinase Inhibitor p21 ; Cyclins/analysis ; Dose-Response Relationship, Drug ; Drug Resistance/genetics ; Epithelial Cells/cytology/*drug effects/metabolism ; Female ; Gene Expression Regulation/drug effects ; Genes ; Humans ; Immunohistochemistry ; Male ; Mesothelioma/metabolism/pathology ; Methylation ; Middle Aged ; Pleural Neoplasms/metabolism/pathology ; Time Factors ; Tumor Suppressor Protein p53/analysis ; }, abstract = {Normal human mesothelial cells from individual donors were studied for susceptibility to asbestos-induction of apoptosis and generation of an extended lifespan population. Such populations were generated after death of the majority of cells and arose from a subset of mesothelial cultures (4/16) whereas fibroblastic cells (5/5) did not develop extended lifespan populations after asbestos exposure. All mesothelial cultures were examined for the presence of SV40 T antigen to obtain information on (i) the presence of SV40 T antigen expression in normal human mesothelial cells and (ii) the relationship between generation of an extended lifespan population and expression of SV40 T antigen. Immunostaining for SV40 T antigen was positive in 2/38 normal human mesothelial cultures. These cultures also had elevated p53 expression. However, the two isolates expressing SV40 T antigen did not exhibit enhanced proliferative potential or develop an extended lifespan population. Asbestos-generated extended lifespan populations were specifically resistant to asbestos-mediated but not to alpha-Fas-induced apoptosis. Deletion of p16Ink4a was shown in 70% of tumor samples. All mesothelioma cell lines examined showed homozygous deletion of this locus which extended to exon 1beta. Extended lifespan cultures were examined for expression of p16Ink4a to establish whether deletion was an early response to asbestos exposure. During their rapid growth phase, extended lifespan cultures showed decreased expression of p16Ink4a relative to untreated cultures, but methylation was not observed, and p16Ink4a expression became elevated when cells entered culture crisis. These data extend the earlier observation that asbestos can generate extended lifespan populations, providing data on frequency and cell type specificity. In addition, this report shows that generation of such populations does not require expression of SV40 T antigen. Extended lifespan cells could represent a population expressing early changes critical for mesothelioma development. Further study of these populations could identify such changes.}, } @article {pmid10234882, year = {1998}, author = {Portaluri, M and Morelli, F}, title = {[Case series of mesotheliomas from hospital archives as contribution to preventive intervention].}, journal = {Annali dell'Istituto superiore di sanita}, volume = {34}, number = {4}, pages = {513-518}, pmid = {10234882}, issn = {0021-2571}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Female ; Humans ; Italy ; Male ; *Mesothelioma/etiology/pathology/prevention & control ; Middle Aged ; Occupational Exposure/adverse effects ; *Pleural Neoplasms/etiology/pathology/prevention & control ; }, abstract = {The clinical charts of 18 patients in the departments of radiotherapy and oncology of the hospital "Casa Sollievo della Sofferenza" (San Giovanni Rotondo, Italy) from 1993 to August 1998, were reviewed. Each case was assigned to first (fine needle aspiration, cytologic exam), second (multiple biopsies during thoracoscopy or laparoscopy) or third (operation) diagnostic level and asbestos exposure was analysed. The age-group was between 21 and 76 years (median 57 years). Three patients were less than 30 years old. The ratio M:F was 17:1. Malignant mesotheliomas were histologically confirmed in 16 cases: 1 patient was classified as malignant pleural tumor (cytology and CT scan), 1 patient as suspicious malignant pleural tumor (only radiological diagnosis) and both were excluded for analysis. We observed 1 case in 1993, 2 in 1994, 3 in 1995, 3 in 1996, 5 in 1997, 2 up to August 1998. Second level diagnosis was assigned to 9 patients and third level to 7 patients. In 9 out 16 cases (56%) the exposure was occupational: 5 ascertained, 2 probable, 2 possible.}, } @article {pmid10231901, year = {1999}, author = {Boillat, MA}, title = {[Synthetic mineral fibers].}, journal = {Schweizerische medizinische Wochenschrift}, volume = {129}, number = {12}, pages = {468-474}, pmid = {10231901}, issn = {0036-7672}, mesh = {Animals ; Humans ; Lung Diseases/*chemically induced/epidemiology ; Lung Neoplasms/*chemically induced/epidemiology/mortality ; Mesothelioma/*chemically induced ; Mineral Fibers/*toxicity ; Occupational Diseases/*chemically induced/epidemiology/mortality ; Pulmonary Fibrosis/chemically induced/epidemiology ; }, abstract = {The group of man-made mineral fibres includes slagwool, glasswool, rockwool, glass filaments and microfibres, as well as refractory ceramic fibres. The toxicity of mineral fibres is determined by several factors such as the diameter (< or = 3-3.5 microns) and the length of the fibres (< 100 microns), their biopersistence, which is much shorter for man-made mineral fibres than for asbestos fibres, their physicochemical structure and surface properties, and the exposure level. The chemical composition of the various types of man-made mineral fibres depends directly on the raw material used to manufacture them. While naturally occurring fibres are crystalline in structure, most man-made mineral fibres are amorphous silicates combined with various metal oxides and additives. Observations using intracavitary administration have provided evidence that some types of man-made mineral fibres are bioactive in cellular and animal experiments and may induce lung tumours and mesothelioma. It is difficult to extrapolate these results to humans since they bypass inhalation, deposition, clearance and translocation mechanisms. Inhalation studies show more realistic results but differences are observed between animal species regarding their sensibility to tumours. There is no firm evidence that exposure to various wools is associated with lung fibrosis, pleural lesions or nonspecific respiratory disease in humans. A possible exception may be mentioned for refractory ceramic fibres. A slightly elevated standard mortality ratio for lung cancer has been documented in large cohorts of workers (USA, Europe and Canada) exposed to man-made mineral fibres, especially in the early technological phase. It is not possible to determine from these data whether the risk of lung cancer is due to the man-made mineral fibres themselves, in particular due to the lack of data on smoking habits. No increased risk of mesothelioma has been demonstrated in these cohorts. Epidemiological data are insufficient at this time concerning neoplastic diseases in refractory ceramic fibres.}, } @article {pmid10230545, year = {1999}, author = {Hamm, M and Rupp, C and Röttger, P and Rathert, P}, title = {[Malignant mesothelioma of the tunica vaginalis testis].}, journal = {Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen}, volume = {70}, number = {3}, pages = {302-305}, doi = {10.1007/s001040050648}, pmid = {10230545}, issn = {0009-4722}, mesh = {Aged ; Diagnosis, Differential ; Humans ; Male ; Mesothelioma/pathology/*surgery ; Orchiectomy ; Testicular Hydrocele/pathology/surgery ; Testicular Neoplasms/pathology/*surgery ; Testis/pathology ; }, abstract = {A case of malignant mesothelioma of the tunica vaginalis testis is reported in a 77-year-old male patient. There was no history of asbestos exposure. Recurrent right hydrocele with a papillar inguinal mass was the main clinical feature. An inguinal radical orchiectomy with en bloc resection of the surrounding tissue was performed. The therapeutic options for this rare, but aggressive neoplasm are discussed. Because of the disappointing results of antineoplastic chemotherapy or radiation therapy, the importance of initial radical surgical treatment with complete excision is emphasized.}, } @article {pmid10224872, year = {1998}, author = {Wysocki, A and Winiarski, M and Leszczyński, M}, title = {[Primary peritoneal mesothelioma--report of two cases].}, journal = {Przeglad lekarski}, volume = {55}, number = {10}, pages = {552-553}, pmid = {10224872}, issn = {0033-2240}, mesh = {Abdomen/diagnostic imaging ; Adult ; Aged ; Female ; Humans ; Male ; Mesothelioma/*diagnosis ; Peritoneal Neoplasms/*diagnosis ; Radiography, Abdominal ; Tomography, X-Ray Computed ; Ultrasonography ; }, abstract = {We report two cases of primary peritoneal mesothelioma. In both of them contact with asbestos was negative. In the first case the patient was hospitalized in another hospital five years earlier. The performed USG and CT of the abdomen revealed the tumor near the spleen. But then the patient was not operated. In the second case the symptoms lasted for several months. In both cases the tumors were nonoperative because of the advanced malignant process.}, } @article {pmid10224596, year = {1999}, author = {Becker, N}, title = {Cancer mortality among arc welders exposed to fumes containing chromium and nickel. Results of a third follow-up: 1989-1995.}, journal = {Journal of occupational and environmental medicine}, volume = {41}, number = {4}, pages = {294-303}, doi = {10.1097/00043764-199904000-00012}, pmid = {10224596}, issn = {1076-2752}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Brain Neoplasms/chemically induced/mortality ; Case-Control Studies ; Chromium/*adverse effects ; Follow-Up Studies ; Germany/epidemiology ; Humans ; Lung Neoplasms/chemically induced/mortality ; Middle Aged ; Neoplasms/chemically induced/*mortality ; Nickel/*adverse effects ; Occupational Exposure/*adverse effects ; Smoking/adverse effects ; *Welding ; }, abstract = {For the historical follow-up study among arc welders exposed to chromium and nickel, which was started in 1980 in Germany, a third follow-up extending the observation period to the years 1989 through 1995 has been carried out. By 1995, of the 1213 welders and 1688 turners (control group) who were originally included in the study, 274 welders and 448 turners had died. Death certificates could be obtained for approximately 96% of the deceased. Results of the evaluation presented in this article showed that cancer mortality remains significantly increased, compared with the general population and the control group, by approximately 35%. There was an elevation of approximately 50% or 60% in mortality from cancers of the respiratory tract, which is also statistically significant. However, this increase is predominantly due to a large excess in mortality from mesothelioma, which is known to be caused chiefly by asbestos exposure. Lung cancer mortality is nonsignificantly increased by approximately 20% to 30%. An indirect assessment of asbestos-related lung cancers and total cancer indicates that the observed increase of mortality might be mainly due to asbestos exposure. Beyond that, no indication of an elevated cancer risk specifically associated with the exposure to welding fumes containing chromium and nickel could be determined.}, } @article {pmid10223568, year = {1999}, author = {Kasseyet, S and Astoul, P and Boutin, C}, title = {Results of a phase II trial of combined chemotherapy for patients with diffuse malignant mesothelioma of the pleura.}, journal = {Cancer}, volume = {85}, number = {8}, pages = {1740-1749}, pmid = {10223568}, issn = {0008-543X}, mesh = {Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use ; Asbestos/adverse effects ; Cisplatin/administration & dosage/adverse effects ; Combined Modality Therapy ; Etoposide/administration & dosage/adverse effects ; Female ; Filgrastim ; Fluorouracil/administration & dosage/adverse effects ; Granulocyte Colony-Stimulating Factor/therapeutic use ; Hematologic Diseases/chemically induced ; Humans ; Immunotherapy ; Leucovorin/therapeutic use ; Male ; Mesothelioma/*drug therapy/etiology/mortality ; Middle Aged ; Mitomycin/administration & dosage/adverse effects ; Pleural Neoplasms/*drug therapy/etiology/mortality ; Prospective Studies ; Recombinant Proteins ; Remission Induction ; Survival Analysis ; Treatment Outcome ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma is associated with a poor prognosis because of its resistance to treatment. The authors conducted a Phase II trial in which two drugs (etoposide and 5-fluorouracil) were added to the Cancer and Leukemia Group B cisplatin-mitomycin regimen in an effort to define a more effective chemotherapy.

METHODS: Forty-five patients with confirmed Stage II malignant pleural mesothelioma were prospectively enrolled in the study. Thirty-one patients received cisplatin 60 mg/m2 on Day 1, 5-fluorouracil 600 mg on Days 1-4, folinic acid 100 mg/m2 on Days 1-4, mitomycin C 10 mg/m2 on Day 3, and etoposide 100 mg/m2 i.v. on Days 1-3, with prophylactic hematopoietic growth factors. Fourteen patients received cisplatin, 5-fluorouracil, folinic acid, and mitomycin C with the protocol unchanged, and oral etoposide 50 mg on Days 1-21 without growth factors (1 cycle every 28 days). Histology included epithelial (in 33 cases), sarcomatous (in 6), mixed (in 3), and unspecified type (in 3).

RESULTS: Two hundred eleven cycles were administered. Treatment was well tolerated and the major toxicity was hematologic: anemia in 30% of cases, neutropenia in 24%, and 2 probable cases of mitomycin-induced pneumonitis. The objective response rate was 38% (17 of 45 were partial responses), and the median response duration was 12 months. The median survival time was 16 months. There were no differences in response or survival between the 31 patients treated with growth factors and the 14 patients treated without them. Survival was slightly better for responders than for nonresponders who had stable disease or progression (20 vs. 10 months, P < 0.05).

CONCLUSIONS: This four-drug combination was effective, with a notably high response rate, acceptable toxicity, and good adherence to protocol doses. The impact on survival was limited.}, } @article {pmid10218542, year = {1999}, author = {Bonn, D}, title = {Asbestos--the legacy lives on.}, journal = {Lancet (London, England)}, volume = {353}, number = {9161}, pages = {1336}, doi = {10.1016/S0140-6736(05)74338-5}, pmid = {10218542}, issn = {0140-6736}, mesh = {Adult ; Asbestos, Crocidolite/*adverse effects ; Asbestos, Serpentine/adverse effects ; Asbestosis/*epidemiology ; Child ; Humans ; Lung Neoplasms/*epidemiology ; Mesothelioma/*epidemiology ; Mining ; South Africa/epidemiology ; }, } @article {pmid10217936, year = {1998}, author = {Boffetta, P}, title = {Health effects of asbestos exposure in humans: a quantitative assessment.}, journal = {La Medicina del lavoro}, volume = {89}, number = {6}, pages = {471-480}, pmid = {10217936}, issn = {0025-7818}, mesh = {Asbestos/*adverse effects ; Asbestosis/etiology ; Carcinogens/*adverse effects ; Humans ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Occupational Diseases/etiology ; Occupational Exposure/*adverse effects ; Pleural Diseases/etiology ; Pleural Neoplasms/etiology ; Pulmonary Fibrosis/etiology ; Risk Factors ; }, abstract = {Asbestos causes four diseases in humans: Lung fibrosis (asbestosis) follows heavy exposure and, in industrialized countries, is mainly a relic of past working conditions. The risk of pleural fibrosis and plaques is likely to be linearly dependent from time since first exposure and is present for all types of asbestos fibres. The diagnostic uncertainties regarding pleural plaques and the substantial degree of misclassification make it difficult to precisely estimate the shape of the dose-response relationship. The risk of lung cancer seems to be linearly related to cumulative asbestos exposure, with an estimated increase in risk of 1% for each fibre/ml-year of exposure. All fibre types seem to exert a similar effect on lung cancer risk; a multiplicative interaction with tobacco smoking has been suggested. Pleural mesothelioma is a malignant neoplasm which is specifically associated with asbestos exposure: the risk is linked with the cubic power of time since first exposure, after allowing for a latency period of 10 years, and depends on the fibre type, as the risk is about three times higher for amphiboles as compared to chrysotile. Environmental exposure to asbestos is also associated with mesothelioma risk.}, } @article {pmid10212648, year = {1999}, author = {Lee, YC and De Klerk, NH and Musk, AW}, title = {Asbestos-related pleural disease in Western Australian gold-miners.}, journal = {The Medical journal of Australia}, volume = {170}, number = {6}, pages = {263-265}, doi = {10.5694/j.1326-5377.1999.tb127749.x}, pmid = {10212648}, issn = {0025-729X}, mesh = {Aged ; Air Pollution/adverse effects ; Asbestos/*adverse effects ; Gold ; Humans ; Male ; Middle Aged ; *Mining ; Occupational Diseases/diagnosis/*etiology ; Occupational Exposure/*adverse effects ; Pleural Diseases/diagnosis/diagnostic imaging/*etiology ; Tomography, X-Ray Computed ; Western Australia ; }, abstract = {Three retired gold-mine workers from Western Australia (WA) were diagnose with asbestos-related pleural disease (two with pleural plaques and one with mesothelioma). Asbestos fibres have been found in air samples from WA gold-mines, and all three patients had worked in these mines (for five to 17 years) and had no other significant known asbestos exposure. To our knowledge, this is the first report of asbestos-related disease in gold-mine workers.}, } @article {pmid10204666, year = {1999}, author = {Boraschi, P and Neri, S and Braccini, G and Gigoni, R and Leoncini, B and Perri, G}, title = {Magnetic resonance appearance of asbestos-related benign and malignant pleural diseases.}, journal = {Scandinavian journal of work, environment & health}, volume = {25}, number = {1}, pages = {18-23}, doi = {10.5271/sjweh.378}, pmid = {10204666}, issn = {0355-3140}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Diagnosis, Differential ; Female ; Humans ; *Magnetic Resonance Imaging ; Male ; Mesothelioma/etiology/*pathology ; Middle Aged ; Occupational Exposure/*adverse effects ; Pleural Diseases/etiology/*pathology ; }, abstract = {OBJECTIVES: This study describes the magnetic resonance findings of benign and malignant pleural diseases in asbestos-exposed subjects.

METHODS: Thirty patients with a history of asbestos exposure and pleural lesions in chest X-rays and computed tomography scans were examined with a 0.5- and a 1.5-T magnetic resonance unit. The examination protocol included cardiac-gated proton density and T2-weighted images, unenhanced and enhanced (Gd-DTPA; 0.1 mmol/ kg) T1-weighted images in the axial plane and sometimes in another orthogonal plane (sagittal or coronal or both). All the magnetic resonance images were reviewed by 3 experienced observers, who visually evaluated morphologic features, signal intensity, and contrast enhancement of pleural lesions. The diagnosis was established by means of percutaneous biopsy, thoracotomy, and combined clinical and radiological follow-up for at least 3 years.

RESULTS: Eighteen patients affected with multiple pleural plaques showed low signal intensity on both unenhanced and enhanced T1-weighted and proton density and T2-weighted images. In 2 of these patients an acute pleural effusion was observed. All the malignant lesions (11 mesotheliomas) and a solitary benign pleural plaque revealed high signal intensity on the proton density and T2-weighted images and inhomogeneous contrast enhancement in the postcontrast T1-weighted images. The sensitivity, specificity, and diagnostic accuracy of the magnetic resonance imaging in classifying a lesion as suggestive of malignancy were 100%, 95% and 97%, respectively.

CONCLUSIONS: The results point out 2 magnetic resonance signal intensity patterns for asbestos-related pleural lesions: (i) low-signal intensity on unenhanced and enhanced T1-weighted and proton density and T2-weighted images for benign plaques and (ii) nonhomogeneous hyperintensity in T2-weighted and enhanced T1-weighted images for malignant mesotheliomas.}, } @article {pmid10193387, year = {1998}, author = {Dhaene, K and Hübner, R and Kumar-Singh, S and Weyn, B and Van Marck, E}, title = {Telomerase activity in human pleural mesothelioma.}, journal = {Thorax}, volume = {53}, number = {11}, pages = {915-918}, pmid = {10193387}, issn = {0040-6376}, mesh = {Electrophoresis, Polyacrylamide Gel ; Humans ; Mesothelioma/*enzymology ; Pleural Neoplasms/*enzymology ; Polymerase Chain Reaction/methods ; Telomerase/*metabolism ; Telomere ; Tumor Cells, Cultured ; }, abstract = {BACKGROUND: Gradual telomere erosion eventually limits the replicative life span of somatic cells and is regarded as an ultimate tumour suppressor mechanism, eliminating cells that have accumulated genetic alterations. Telomerase, which has been found in over 85% of human cancers, elongates telomeres and may be required for tumorigenesis by the process of immortalisation. Malignant mesothelioma is an incurable malignancy with a poor prognosis. The disease becomes symptomatic decades after exposure to carcinogenic asbestos fibres, suggesting the long term survival of pre-malignant cell clones. This study investigated the presence of telomerase in pleural malignant mesothelioma, which may be the target for future anti-telomerase drugs.

METHODS: Telomerase activity was semiquantitatively measured in extracts from 22 primary pleural mesotheliomas, two benign solitary fibrous tumours of the pleura, four mesothelioma cell lines, and six short term mesothelial cell cultures from normal pleura using a non-isotopic dilution assay of the telomeric repeat amplification protocol.

RESULTS: Twenty of the 22 primary mesotheliomas (91%) and all tumour derived mesothelioma cell lines were telomerase positive. Different levels of enzyme activity were observed in the tumours of different histological subtypes. Telomerase activity could not be detected in the six normal mesothelial cell cultures or in the two mesotheliomas. Both benign solitary fibrous tumours showed strong telomerase activity.

CONCLUSIONS: Telomerase activity is found in a high proportion of mesotheliomas and anti-telomerase drugs might therefore be useful clinically. The results are consistent with the hypothesis that telomerase activity may be a feature of carcinogenesis in mesotheliomas and possibly in many other cancers.}, } @article {pmid10188871, year = {1999}, author = {Okayasu, R and Wu, L and Hei, TK}, title = {Biological effects of naturally occurring and man-made fibres: in vitro cytotoxicity and mutagenesis in mammalian cells.}, journal = {British journal of cancer}, volume = {79}, number = {9-10}, pages = {1319-1324}, pmid = {10188871}, issn = {0007-0920}, support = {CA 71438/CA/NCI NIH HHS/United States ; ES 05876/ES/NIEHS NIH HHS/United States ; ES06831/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Asbestos, Amphibole/*toxicity ; Asbestos, Serpentine/*toxicity ; Cell Line ; Cell Survival ; Ceramics/*toxicity ; Cricetinae ; Humans ; Hybrid Cells ; Kaolin/*toxicity ; Mineral Fibers/*toxicity ; Mutagenicity Tests ; Zeolites/*toxicity ; }, abstract = {Cytotoxicity and mutagenicity of tremolite, erionite and the man-made ceramic (RCF-1) fibre were studied using the human-hamster hybrid A(L) cells. Results from these fibres were compared with those of UICC Rhodesian chrysotile fibres. The A(L) cell mutation assay, based on the S1 gene marker located on human chromosome 11, the only human chromosome contained in the hybrid cell, has been shown to be more sensitive than conventional assays in detecting deletion mutations. Tremolite, erionite and RCF-1 fibres were significantly less cytotoxic to A(L) cells than chrysotile. Mutagenesis studies at the HPRT locus revealed no significant mutant yield with any of these fibres. In contrast, both erionite and tremolite induced dose-dependent S1- mutations in fibre-exposed cells, with the former inducing a significantly higher mutant yield than the latter fibre type. On the other hand, RCF-1 fibres were largely non-mutagenic. At equitoxic doses (cell survival at approximately 0.7), erionite was found to be the most potent mutagen among the three fibres tested and at a level comparable to that of chrysotile fibres. These results indicate that RCF-1 fibres are non-genotoxic under the conditions used in the studies and suggest that the high mesothelioma incidence previously observed in hamster may either be a result of selective sensitivity of hamster pleura to fibre-induced chronic irritation or as a result of prolonged fibre treatment. Furthermore, the relatively high mutagenic potential for erionite is consistent with its documented carcinogenicity.}, } @article {pmid10086201, year = {1999}, author = {Finkelstein, MM and Dufresne, A}, title = {Inferences on the kinetics of asbestos deposition and clearance among chrysotile miners and millers.}, journal = {American journal of industrial medicine}, volume = {35}, number = {4}, pages = {401-412}, doi = {10.1002/(sici)1097-0274(199904)35:4<401::aid-ajim12>3.0.co;2-4}, pmid = {10086201}, issn = {0271-3586}, mesh = {Aged ; Aged, 80 and over ; Asbestos, Amphibole/*pharmacokinetics ; Asbestos, Serpentine/*pharmacokinetics ; Asbestosis/metabolism/*pathology ; Case-Control Studies ; Humans ; Lung Neoplasms/metabolism/*pathology ; Male ; Mesothelioma/metabolism/*pathology ; Metabolic Clearance Rate ; Microscopy, Electron ; Middle Aged ; Mineral Fibers ; Mining ; Multivariate Analysis ; Regression Analysis ; }, abstract = {BACKGROUND: The health effects of asbestos are intimately related to the fate of inhaled fibers in the lungs. The kinetics of asbestos fibers have been studied primarily in rodents. The objective of this study was to explore the application of these kinetic models to human autopsy data.

METHODS: We analyzed the asbestos fiber content of the lungs of 72 Quebec chrysotile miners and millers and 49 control subjects using analytical transmission electron microscopy. Statistical methods included standard multivariate linear regression and locally weighted regression methods.

RESULTS: The lung burdens of asbestos bodies and chrysotile and tremolite fibers were correlated, as were the concentrations of short, medium, and long fibers of each asbestos variety. There were significant associations between the duration of occupational exposure and the burdens of chrysotile and tremolite. The concentration of chrysotile decreased with the time since last exposure but the concentration of tremolite did not. The clearance rate varied inversely with the length of chrysotile fibers. For fibers greater than 10 mu in length the clearance half-time was estimated to be 8 years.

CONCLUSIONS: The patterns in our data are compatible with both of the hypotheses suggested from rodent experiments; the existence of a long-term sequestration compartment and overload of clearance mechanisms in this compartment.}, } @article {pmid10052294, year = {1999}, author = {Kurumatani, N and Natori, Y and Mizutani, R and Kumagai, S and Haruta, M and Miura, H and Yonemasu, K}, title = {A historical cohort mortality study of workers exposed to asbestos in a refitting shipyard.}, journal = {Industrial health}, volume = {37}, number = {1}, pages = {9-17}, doi = {10.2486/indhealth.37.9}, pmid = {10052294}, issn = {0019-8366}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Asbestosis/etiology/mortality ; Cause of Death ; Cohort Studies ; Humans ; Japan/epidemiology ; Lung Neoplasms/etiology/mortality ; Male ; Mesothelioma/etiology/mortality ; Middle Aged ; Mortality/*trends ; *Occupational Exposure ; Pancreatic Neoplasms/etiology/mortality ; Ships ; }, abstract = {To investigate the risks of developing asbestos-related diseases we conducted a historical cohort mortality study on 249 ship repair workers (90 laggers and 159 boiler repairers) in a single U.S. Navy shipyard in Japan. We successfully identified the vital status of 87 (96.7%) laggers and 150 (94.3%) boiler repairers, and, of these, 49 (56.3%) and 65 (43.3%) died, respectively, during the follow-up period from 1947 till the end of 1996. Our in-person interviews with some of the subjects clarified that asbestos exposure was considered to be substantially high in the 1950-60s, decreased thereafter gradually but remained till 1979 in the shipyard. The laggers, who had handled asbestos materials directly, showed a significantly elevated SMR of 2.75 (95% C.I.: 1.08-6.48) for lung cancer. The risk developing the disease was greater in the laggers after a 20-year latency (SMR = 3.42). Pancreatic cancer yielded a greater SMR than unity (7.78, 90% C.I.: 2.07-25.19) in a longer working years group. Four laggers died from asbestosis. The boiler repairers, who had many chances for secondary exposure to asbestos and a few for direct exposure, showed no elevation of the SMR of lung cancer overall, but there was a borderline statistically significant SMR of 2.41 (90% C.I.: 1.05-5.45) in a longer working years group. One boiler repairer died from mesothelioma and four from asbestosis.}, } @article {pmid10036367, year = {1998}, author = {Castleman, B and Dement, J and Frank, AL and Frumkin, H and Giannasi, F and Gochfeld, M and Goldstein, BD and Grandjean, P and Greenberg, M and LaDou, J and Lemen, RA and Levy, BS and Maltoni, C and McDiarmid, M and Silbergeld, EK and Teitelbaum, DT and Thebaud-Mony, A and Upton, AC and Wegman, DH}, title = {Salud Ocupacional.}, journal = {International journal of occupational and environmental health}, volume = {4}, number = {2}, pages = {131-133}, doi = {10.1179/oeh.1998.4.2.131}, pmid = {10036367}, issn = {1077-3525}, mesh = {*Academies and Institutes ; Asbestos/*adverse effects ; Conflict of Interest ; Humans ; Mesothelioma/*chemically induced ; Occupational Exposure/*adverse effects ; Peer Review, Research/*standards ; *Periodicals as Topic ; }, } @article {pmid10028894, year = {1999}, author = {Burdorf, A and Swuste, P}, title = {An expert system for the evaluation of historical asbestos exposure as diagnostic criterion in asbestos-related diseases.}, journal = {The Annals of occupational hygiene}, volume = {43}, number = {1}, pages = {57-66}, pmid = {10028894}, issn = {0003-4878}, mesh = {Asbestosis/*diagnosis ; Decision Trees ; *Expert Systems ; Humans ; Lung Neoplasms/*diagnosis/etiology ; Mesothelioma/*diagnosis/etiology ; Netherlands ; Occupational Diseases/diagnosis ; Occupational Exposure/*adverse effects ; Retrospective Studies ; Workers' Compensation ; }, abstract = {Compensation schemes for asbestos-related diseases have developed different strategies for attributing a specific disease to occupational exposure to asbestos in the past. In the absence of quantitative exposure information that allows a valid estimate of an individual's historical exposure, general guidelines are required to retrospectively evaluate asbestos exposure. A risk matrix has been developed that contains qualitative information on the proportion of workers exposed and the level of exposure in particular industries over time. Based on this risk matrix, stepwise decision trees were formulated for decisions regarding the decisive role of historical asbestos exposure in case ascertainment of asbestosis and mesothelioma. Application of decision schemes will serve to speed up the process of verifying compensation claims and also contribute to a uniform decision-making process in legal procedures.}, } @article {pmid10028551, year = {1999}, author = {Bégin, R}, title = {[Asbestos exposure and pleuropulmonary cancer].}, journal = {Revue des maladies respiratoires}, volume = {16 Suppl 2}, number = {}, pages = {S34-41}, pmid = {10028551}, issn = {0761-8425}, mesh = {Asbestos/*adverse effects ; Asbestosis/complications/physiopathology ; Humans ; Lung Neoplasms/*etiology/physiopathology ; Mesothelioma/*etiology/physiopathology ; Occupational Diseases/*etiology/physiopathology ; Occupational Exposure ; Pleural Neoplasms/*etiology/physiopathology ; Risk Assessment ; }, abstract = {Pleuropulmonary cancers are recognized asbestos-related diseases. Mesothelioma occurs almost uniquely in individuals exposed to asbestos whereas lung cancer is strongly associated with smoking. If the asbestos exposure is sufficient however, the incidence of lung cancer is higher than would be expected from the smoking effect alone. For lung cancer in asbestos workers, asbestosis is not a prerequisite for recognition as an occupation related disease. The intensity and duration of exposure to asbestos are factors associated with higher risk of lung cancer. These factors can be estimated on the basis of the work history or, when necessary, by analyzing mineral dust from available lung tissues.}, } @article {pmid10027347, year = {1999}, author = {Peto, J and Decarli, A and La Vecchia, C and Levi, F and Negri, E}, title = {The European mesothelioma epidemic.}, journal = {British journal of cancer}, volume = {79}, number = {3-4}, pages = {666-672}, pmid = {10027347}, issn = {0007-0920}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Disease Outbreaks/*statistics & numerical data ; Europe/epidemiology ; Forecasting ; Humans ; Incidence ; Male ; Mesothelioma/*mortality ; Middle Aged ; Mortality/trends ; Pleural Neoplasms/*mortality ; Risk Assessment ; }, abstract = {Projections for the period 1995-2029 suggest that the number of men dying from mesothelioma in Western Europe each year will almost double over the next 20 years, from 5000 in 1998 to about 9000 around 2018, and then decline, with a total of about a quarter of a million deaths over the next 35 years. The highest risk will be suffered by men born around 1945-50, of whom about 1 in 150 will die of mesothelioma. Asbestos use in Western Europe remained high until 1980, and substantial quantities are still used in several European countries. These projections are based on the fit of a simple age and birth cohort model to male pleural cancer mortality from 1970 to 1989 for six countries (Britain, France, Germany, Italy, The Netherlands and Switzerland) which together account for three-quarters of the population of Western Europe. The model was tested by comparing observed and predicted numbers of deaths for the period 1990-94. The ratio of mesothelioma to recorded pleural cancer mortality has been 1.6:1 in Britain but was assumed to be 1:1 in other countries.}, } @article {pmid10026475, year = {1998}, author = {Henneberger, PK and Lax, MB}, title = {Lung cancer mortality in a cohort of older pulp and paper workers.}, journal = {International journal of occupational and environmental health}, volume = {4}, number = {3}, pages = {147-154}, doi = {10.1179/oeh.1998.4.3.147}, pmid = {10026475}, issn = {1077-3525}, mesh = {Cause of Death ; Cohort Studies ; Follow-Up Studies ; Humans ; Lung Neoplasms/etiology/*mortality ; Male ; Middle Aged ; New Hampshire/epidemiology ; Occupational Diseases/etiology/*mortality ; Occupational Exposure/adverse effects ; *Paper ; Proportional Hazards Models ; Risk Factors ; Smoking/adverse effects ; Sulfites/adverse effects ; Time Factors ; }, abstract = {The occurrence of deaths due to lung cancer was studied among 883 white male workers from a pulp and paper company in northern New Hampshire. All subjects had participated in a longitudinal study of respiratory morbidity, and data from interviews were used to construct lifetime cigarette smoking and occupational histories. Most of the subjects had entered follow-up in the 1960s and, at that time, their mean age was 51 years and they had worked for the pulp and paper company a mean of 25 years. By the end of follow-up in 1992, the 512 deceased subjects included 35 whose underlying cause of death had been lung cancer. With an internal comparison using the Cox proportional-hazards model, the hazard ratio for sulfite pulp mill work was 2.5 (95% CI 1.3-4.9), while controlling for the effects of age, cigarette smoking, and work in other parts of the pulping operation. In addition, the hazard ratio for the combination of >35 pack-years of smoking and >10 years sulfite mill work was greater than the product of the hazard ratios for each factor alone. While these findings are consistent with past asbestos exposure in the sulfite pulp mill environment, the absence of mesothelioma cases is inconsistent with this type of exposure.}, } @article {pmid10025883, year = {1998}, author = {Vasilieva, LA and Pylev, LN and Rovensky, YA}, title = {Pathogenesis of experimentally induced asbestos mesothelioma in rats.}, journal = {Cancer letters}, volume = {134}, number = {2}, pages = {209-216}, doi = {10.1016/s0304-3835(98)00255-9}, pmid = {10025883}, issn = {0304-3835}, mesh = {Animals ; Asbestos ; Carcinogens ; Cell Division ; Cell Transformation, Neoplastic ; Female ; Injections ; Male ; Mesothelioma/chemically induced/*pathology ; Microscopy, Electron, Scanning ; Neoplasms, Experimental/chemically induced/*pathology ; Pleura ; Pleural Neoplasms/chemically induced/*pathology ; Rats ; Rats, Wistar ; }, abstract = {Fragments of parietal and visceral pleura were studied by total films preparation, light microscopy and SEM at different times after intrapleural injection of asbestos in Wistar rats. Pleural rat mesothelium in histological slices consists normally of one layer of oblong cells. By SEM the cells are flat and coated with microvilli of different lengths. In total films the parietal mesothelium was composed of large polygonal cells covering intercostal spaces and small cells covering spaces over the ribs. Inflammatory reaction and permanent pathological regenerative processes were observed in the mesothelium during 24 months after inoculation of asbestos fibres. Different lesions which we regarded as preneoplastic or premesotheliomatous were observed against the background of or without these processes. They were diffuse irregular hyperplasia and proliferation of epithelium-like or fibroblast-like cells and focal nodous proliferates composed of such cells with various morphological structures. The number of thymidine-labelled cells was significantly more inside the proliferates than in the surrounding tissue. They were confirmed by SEM and histological slices of the same fields. Chronic pathological regeneration of pleural mesothelium could be the background against which preneoplastic lesions and mesotheliomas develop easily.}, } @article {pmid9987816, year = {1998}, author = {Schneider, J and Rödelsperger, K and Brückel, B and Kayser, K and Woitowitz, HJ}, title = {Environmental exposure to tremolite asbestos: pleural mesothelioma in two Turkish workers in Germany.}, journal = {Reviews on environmental health}, volume = {13}, number = {4}, pages = {213-220}, doi = {10.1515/reveh.1998.13.4.213}, pmid = {9987816}, issn = {0048-7554}, mesh = {Asbestos, Amphibole/*adverse effects ; Germany ; Humans ; Lung Neoplasms/*chemically induced/pathology ; Male ; Mesothelioma/*chemically induced/pathology ; Middle Aged ; Occupational Diseases/*chemically induced/pathology ; Turkey/ethnology ; }, abstract = {This report concerns two Turkish immigrant workers, aged 50 and 59, who developed histologically confirmed diffuse malignant mesothelioma in the absence of obvious occupational exposure to asbestos in Germany. Both patients had spent their childhood in central Anatolia, Turkey, where the presence of tremolite asbestos in the environment has been described. In both patients, the lung-dust burden showed a high concentration of amphibole fibers (186 x 10(6) resp. 59 x 10(6) per gram dry tissue), mainly classified as actionolite/tremolite fibers in scanning transmission electron microscopy. In both patients, the disease was thus attributed to early environmental exposure to tremolite asbestos.}, } @article {pmid9987554, year = {1999}, author = {Rees, D and Myers, JE and Goodman, K and Fourie, E and Blignaut, C and Chapman, R and Bachmann, MO}, title = {Case-control study of mesothelioma in South Africa.}, journal = {American journal of industrial medicine}, volume = {35}, number = {3}, pages = {213-222}, doi = {10.1002/(sici)1097-0274(199903)35:3<213::aid-ajim1>3.0.co;2-r}, pmid = {9987554}, issn = {0271-3586}, mesh = {Asbestos/*adverse effects/classification ; *Carcinogens ; Case-Control Studies ; Confidence Intervals ; Environmental Exposure/*adverse effects ; Female ; Humans ; Logistic Models ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Exposure/adverse effects ; Odds Ratio ; Peritoneal Neoplasms/epidemiology/etiology ; Pleural Neoplasms/epidemiology/etiology ; South Africa/epidemiology ; Sputum ; }, abstract = {BACKGROUND: South Africa has, uniquely, mined, transported, and used crocidolite, amosite, and chrysotile. A multicenter case-control study was done in South Africa to examine the details of asbestos exposure in cases and controls, and to calculate relative risks for level of certainty of asbestos exposure, nature of exposure (e.g., environmental, occupational) and fiber type.

METHODS: Cases and controls (one cancer and one medical per case) were collected by six study centers from referral hospitals, and exposure information was collected by interviewing cases and controls in life.

RESULTS: One hundred and twenty-three cases were accepted into the study. None had purely chrysotile exposure. Twenty-three cases had mined Cape crocidolite; three had mined amosite; and three Transvaal crocidolite plus amosite. A minimum of 22 of the cases had exclusively environmental exposure, 20 were from the NW Cape crocidolite mining area. The relative risks associated with environmental exposure in the NW Cape (crocidolite) were larger than for environmental exposure in the NE Transvaal (amosite and crocidolite): 21.9 vs. 7.1 and 50.9 vs. 12.0 for the cancer control and medical control datasets, respectively.

CONCLUSIONS: The results confirm the importance of environmental exposure in the Cape crocidolite mining area, the relative paucity of cases linked to amosite, the rarity of chrysotile cases and are consistent with a fiber gradient in mesotheliomagenic potential for South African asbestos with crocidolite > amosite > chrysotile.}, } @article {pmid9931667, year = {1998}, author = {Schirren, J and Muley, T and Schneider, P and Trainer, C and Bülzebruck, H and Dienemann, H and Vogt-Moykopf, I}, title = {[Treatment strategy in pleural mesothelioma].}, journal = {Langenbecks Archiv fur Chirurgie. Supplement. Kongressband. Deutsche Gesellschaft fur Chirurgie. Kongress}, volume = {115}, number = {}, pages = {498-506}, pmid = {9931667}, issn = {0942-2854}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Combined Modality Therapy ; Female ; Humans ; Male ; Mesothelioma/mortality/pathology/*surgery ; Middle Aged ; Neoplasm Staging ; Pleural Neoplasms/mortality/pathology/*surgery ; Prognosis ; Survival Rate ; }, abstract = {The development of diffuse malignant pleural mesothelioma is associated with exposure to asbestos. The surgical treatment comprises a radical pleuropneumonectomy with resection of the pericardium and diaphragm (P3D) or palliative pleurectomy/decortication of the tumor. The prognosis in general is poor. P3D is most effective in patients with epithelial mesothelioma at an early stage. Complete resection has the best prognosis. Palliative tumor decortication is restricted to symptomatic patients with acceptable performance status. The prognosis of patients after radical resection is not significantly different from patients with pleurectomy/decortication. Preliminary results of multimodal therapy concepts, including additional chemo- and/or radiotherapy, suggest an improvement in survival. Nevertheless, so far treatment has been focused on the palliation of clinical symptoms like pain and dyspnee.}, } @article {pmid9924454, year = {1998}, author = {Järvholm, B and Sandén, A}, title = {Lung cancer and mesothelioma in the pleura and peritoneum among Swedish insulation workers.}, journal = {Occupational and environmental medicine}, volume = {55}, number = {11}, pages = {766-770}, pmid = {9924454}, issn = {1351-0711}, mesh = {Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Cohort Studies ; Follow-Up Studies ; Humans ; Lung Neoplasms/*epidemiology/etiology ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Exposure/adverse effects ; Peritoneal Neoplasms/*epidemiology/etiology ; Pleural Neoplasms/*epidemiology/etiology ; Risk Assessment ; Risk Factors ; Smoking/adverse effects ; Surveys and Questionnaires ; Sweden/epidemiology ; }, abstract = {OBJECTIVES: To estimate the risk of cancer and death in Swedish insulation workers some years after their exposure to asbestos had stopped. One hypothesis was that the risk of lung cancer would tend to decrease some years after the exposure had ended.

METHODS: In a cohort study the cancer morbidity and cause of death was investigated in 248 insulation workers and compared with the corresponding morbidity and mortality in the general population. Due to stringent regulations, exposure to asbestos of all types had almost ended in Sweden in the mid-1970s. Through a questionnaire, surviving insulation workers were asked about their exposure to asbestos and their smoking habits.

RESULTS: Between 1970 and 1994 there were 86 deaths compared with the 46.0 expected (standardised incidence ratio (SIR) 1.9; 95% confidence interval (95% CI) 1.5 to 2.3), the increase was mainly due to an increased cancer mortality. The morbidity was increased for lung cancer (11 cases v 2.5 expected (SIR 4.4; 95% CI 2.2 to 7.9)), peritoneal mesothelioma (seven cases; no expected incidence could be calculated as the occurrence is too rare in the general population), cancer in pancreas (five cases v 0.7 expected (SIR 7.1; 95% CI 2.3 to 16.7)). No cases of pleural mesothelioma were found. The risk of lung cancer did not tend to approach that of the general population after the exposure to asbestos decreased.

CONCLUSIONS: In the 1980s and the early 1990s, Swedish insulation workers still have a highly increased risk of diseases related to asbestos. The attributable risk for death and cancer was about 50%. The study also confirms the previous finding that mesothelioma in insulation workers seems to be situated in the peritoneum more often than in the pleura.}, } @article {pmid9924453, year = {1998}, author = {Ilg, AG and Bignon, J and Valleron, AJ}, title = {Estimation of the past and future burden of mortality from mesothelioma in France.}, journal = {Occupational and environmental medicine}, volume = {55}, number = {11}, pages = {760-765}, pmid = {9924453}, issn = {1351-0711}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos, Serpentine/adverse effects ; Cohort Studies ; Female ; Forecasting/methods ; France/epidemiology ; Humans ; Male ; Mesothelioma/etiology/*mortality ; Middle Aged ; Mortality/trends ; }, abstract = {OBJECTIVES: Firstly to evaluate future mortality from mesothelioma in France with an age-period-cohort approach and evaluate different hypotheses on risk of mesothelioma for the most recent birth cohort. Secondly to compare the results with a British and an American study. Thirdly to study if any trends were detectable on data for women which would be consistent with the consequences of increasing environmental exposure to asbestos.

METHODS: Estimates of mortality from mesothelioma among men and women in France from 1950 to 1995 were based on the analysis of the pleural cancer mortality data coded 163 in the ninth revision of the international classification of diseases (ICD-9). Correction factors were used to derive the mortality from mesothelioma from these data, based on two regional registries. The analysis of the past mortality data has been performed by an age-cohort model (with a maximum likelihood technique). Predictions of deaths from mesothelioma over the next 50 years were based on four different assumptions on the risk of death from mesothelioma in future birth cohorts.

RESULTS: The predicted lifetime probability of dying from mesothelioma increases until the last birth cohort 1964-8 among men whereas it decreases strongly from the 1954-8 birth cohort among women. The projected numbers of deaths from mesothelioma in France until 2020 are similar, whichever hypothesis is considered: around 20,000 deaths from mesothelioma might occur among men and 2900 among women from 1996 to 2020.

CONCLUSIONS: French data show an increasing lifetime probability of death from mesothelioma in the more recent male cohorts. Although the mortality burden can be predicted until 2020, and is intermediate between the United Kingdom and United States estimates, there is still high uncertainty on the figures after 2020. No increase is found in women, and this does not support the hypothesis that current environmental exposure to asbestos could be associated with a detectable risk of death. Specific surveillance should be set up to monitor future trends or their absence.}, } @article {pmid9924446, year = {1998}, author = {Magnani, C and Mollo, F and Paoletti, L and Bellis, D and Bernardi, P and Betta, P and Botta, M and Falchi, M and Ivaldi, C and Pavesi, M}, title = {Asbestos lung burden and asbestosis after occupational and environmental exposure in an asbestos cement manufacturing area: a necropsy study.}, journal = {Occupational and environmental medicine}, volume = {55}, number = {12}, pages = {840-846}, pmid = {9924446}, issn = {1351-0711}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos, Crocidolite/*adverse effects ; Asbestos, Serpentine/*adverse effects ; Asbestosis/*epidemiology/pathology ; Construction Materials/adverse effects ; Environmental Exposure/adverse effects ; Female ; Humans ; Italy/epidemiology ; Male ; Middle Aged ; Occupational Exposure/adverse effects ; }, abstract = {OBJECTIVE: The largest Italian asbestos cement factory had been active in Casale Monferrato until 1986: in previous studies a substantial increase in the incidence of pleural mesothelioma was found among residents without occupational exposure to asbestos. To estimate exposure to asbestos in the population, this study evaluated the presence of histological asbestosis and the lung burden of asbestos fibres (AFs) and asbestos bodies (ABs).

METHODS: The study comprises the consecutive series of necropsies performed at the Hospital of Casale Monferrato between 1985 and 1988. A sample of lung parenchima was collected and stored for 48 out of 55 necropsies. The AF concentration was measured with a TEM electron microscope with x ray mineralogical analysis. The ABs were counted and fibrosis evaluated by optical microscopy. The nearest relative of each subject was interviewed on occupational and residential history. Mineralogical and histological analyses and interviews were conducted in 1993-4.

RESULTS: Statistical analyses included 41 subjects with AF, AB count, and interview. Subjects without occupational exposure who ever lived in Casale Monferrato had an average concentration of 1500 AB/g dried weight (gdw); Seven of 18 presented with asbestosis or small airway lung disease (SAL). G2 asbestosis was diagnosed in two women with no occupational asbestos exposure. One of them had been teaching at a school close to the factory for 12 years. Ten subjects had experienced occupational asbestos exposure, seven in asbestos cement production: mean concentrations were 1.032 x 10(6) AF/gdw and 96,280 AB/gdw. Eight of the 10 had asbestosis or SAL.

CONCLUSION: The high concentration of ABs and the new finding of environmental asbestosis confirm that high asbestos concentration was common in the proximity of the factory. Subjects not occupationally exposed and ever living in Casale Monferrato tended to have higher AB concentration than subjects never living in the town (difference not significant). The concentrations of ABs and AFs were higher than those found in other studies on nonoccupationally exposed subjects.}, } @article {pmid9923026, year = {1998}, author = {Begin, R}, title = {[Asbestos exposure and pleuropulmonary cancer].}, journal = {Revue des maladies respiratoires}, volume = {15}, number = {6}, pages = {723-730}, pmid = {9923026}, issn = {0761-8425}, mesh = {Asbestos/*adverse effects ; Carcinogens/*adverse effects ; Humans ; Lung Neoplasms/*etiology/physiopathology ; Mesothelioma/*etiology/physiopathology ; *Occupational Exposure ; Pleural Neoplasms/*etiology/physiopathology ; Risk Assessment ; Time Factors ; }, abstract = {Pleuropulmonary cancers are recognized asbestos-related diseases. Mesothelioma occurs almost uniquely in individuals exposed to asbestos whereas lung cancer is strongly associated with smoking. If the asbestos exposure is sufficient however, the incidence of lung cancer is higher than would be expected from the smoking effect alone. For lung cancer in asbestos workers, asbestosis is not a prerequisite for recognition as an occupation-related disease. The intensity and duration of exposure to asbestos are factors associated with higher risk of lung cancer. These factors can be estimated on the basis of the work history or, when necessary, by analyzing mineral dust from available lung tissues.}, } @article {pmid9894545, year = {1999}, author = {Finkelstein, MM}, title = {Maintenance work and asbestos-related cancers in the refinery and petrochemical sector.}, journal = {American journal of industrial medicine}, volume = {35}, number = {2}, pages = {201-205}, doi = {10.1002/(sici)1097-0274(199902)35:2<201::aid-ajim13>3.0.co;2-f}, pmid = {9894545}, issn = {0271-3586}, mesh = {Asbestos/*adverse effects ; *Chemical Industry ; Humans ; Lung Neoplasms/*chemically induced/diagnostic imaging ; *Maintenance ; Mesothelioma/chemically induced ; Occupational Diseases/*chemically induced/diagnostic imaging ; Occupational Exposure ; *Petroleum ; Radiography, Thoracic ; Smoking/adverse effects ; }, } @article {pmid9885009, year = {1998}, author = {Langner, K and Schäfer, R and Müller, KM and Göller, T}, title = {[Synovial sarcoma of the pericardium].}, journal = {Der Pathologe}, volume = {19}, number = {6}, pages = {442-446}, doi = {10.1007/s002920050310}, pmid = {9885009}, issn = {0172-8113}, mesh = {Adult ; Asbestosis/pathology ; Biomarkers, Tumor/analysis ; Diagnosis, Differential ; Heart Neoplasms/*pathology ; Humans ; Male ; Pericardium/*pathology ; Sarcoma, Synovial/*pathology ; }, abstract = {A precordial tumor of the pericardium was radiologically diagnosed as the cause of an untypical clinical picture of heart disease in a 41-year-old soldier. As the patient had an increased asbestos exposure due to his profession, he was admitted to operation under the tentative diagnosis of a pericardial mesothelioma and the question of an occupational disease (BK 4105). Microscopic and immunohistochemical findings are compatible with the diagnosis of a synovial sarcoma of the pericardium. The present immunohistochemical marker spectrum allowed a reliable differentiation between synovial sarcoma and pericardial mesothelioma, which is more frequent than synovial sarcoma. The epithelioid component was determined using the following antibodies: MNF 116, CK 19, CK 7, EMA and Ber EP-4 were positive while Factor VIII, Calretinin, S100, Vimentin, CEA, CD 31, bcl-2 and HBA-71 were negative. The sarcomatous component was determined with antibodies to Vimentin, bcl-2 and HBA-71 which were positive, and to MNF 116, CK 19, CK 7, Factor VIII, Calretinin, S100, EMA, CEA, Ber EP-4 and CD 31 which were negative. Synovial sarcomas of the pericardium in the lower anterior mediastinum or the myocardium are exceedingly rare. A causal relationship between tumor formation and an increased asbestos exposure--similar to the epidemiologically based experiences with pericardial mesothelioma--is not likely. Primary extrapericardial synovial sarcoma could be excluded.}, } @article {pmid9884740, year = {1999}, author = {Cocco, P and Dosemeci, M}, title = {Peritoneal cancer and occupational exposure to asbestos: results from the application of a job-exposure matrix.}, journal = {American journal of industrial medicine}, volume = {35}, number = {1}, pages = {9-14}, doi = {10.1002/(sici)1097-0274(199901)35:1<9::aid-ajim2>3.0.co;2-v}, pmid = {9884740}, issn = {0271-3586}, mesh = {Aged ; *Asbestos ; *Death Certificates ; Epidemiologic Methods ; Female ; Humans ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Occupational Diseases/*epidemiology ; *Occupational Exposure ; Peritoneal Neoplasms/*epidemiology ; United States/epidemiology ; }, abstract = {BACKGROUND: Because of the rarity of peritoneal mesothelioma, occupational risks associated with it have seldom been studied, particularly among women. In this respect, death certificates databases may provide numbers large enough for analysis, although the International Classification of Diseases, 9th revision (ICD-9) does not single out mesothelioma from the rest of peritoneal cancers. The aim of this paper is twofold: to explore occupational risks of peritoneal cancer among men and women, and to test the performance of a job-exposure matrix in detecting its association with asbestos exposure using the occupation and industry reported in the death certificate.

METHODS: From a large database containing information on the 1984-1992 death certificates of 24 U.S. states, we identified 657 deaths from peritoneal cancer and 6,570 controls who died from non-malignant diseases, 1:10 matched by region, gender, race, and 5-year age group.

RESULTS: Occupations at risk included insulators among men, and machine operators among women. Among men, we found a significant increase in risk associated with employment in manufacturing industries, such as industrial and miscellaneous chemicals; miscellaneous non-metallic mineral and stone products; construction and material handling machines; and electrical machinery, equipment, and supplies; as well as in services to dwellings and other buildings. Industries at increased risk among women included elementary and secondary schools; miscellaneous retail stores; and publishing and printing. Our job-exposure matrix classified 17 male cases and 3 controls in the high probability category of exposure to asbestos (OR = 61.6). Among men, risk of peritoneal cancer increased significantly by probability and intensity of exposure to asbestos. No such pattern was observed among women. The job-exposure matrix did not classify any female subjects in the high probability or intensity of asbestos exposure.

DISCUSSION: This study provides evidence that death certificate data and job-exposure matrices are useful tools to observe well-established associations, such as the one existing between peritoneal cancer and asbestos exposure among men, in spite of crude information, disease misclassification, and occupational misclassification. These factors are more likely to preclude meaningful results among women.}, } @article {pmid9884739, year = {1999}, author = {Tulchinsky, TH and Ginsberg, GM and Iscovich, J and Shihab, S and Fischbein, A and Richter, ED}, title = {Cancer in ex-asbestos cement workers in Israel, 1953-1992.}, journal = {American journal of industrial medicine}, volume = {35}, number = {1}, pages = {1-8}, doi = {10.1002/(sici)1097-0274(199901)35:1<1::aid-ajim1>3.0.co;2-5}, pmid = {9884739}, issn = {0271-3586}, mesh = {Aged ; Aged, 80 and over ; *Asbestos ; Cohort Studies ; Humans ; Incidence ; Israel/epidemiology ; Lung Neoplasms/*epidemiology/mortality ; Male ; Mesothelioma/*epidemiology/mortality ; Middle Aged ; Occupational Diseases/*epidemiology/mortality ; }, abstract = {A cohort of 3,057 male workers employed in an asbestos-cement plant using 90% chrysotile-10% crocidolite, located in Northern Israel, was followed from 1953-1992 for incidence and mortality from cancer. In the years 1978-1992, the cohort had an elevated risk for all malignant neoplasms combined (n = 153, SIR = 117, ns), lung cancer (n = 28, SIR = 135, ns), mesothelioma (n = 21; SIR > 5000, p < .0001), unspecified pleural cancer (n = 5; SIR = 278, P < .0001), and liver cancer (n = 7, SIR 290, ns). Risks for colo-rectal (n = 19; SIR = 79, ns), bladder (n = 12, SIR 69) and renal cancers (n = 5, SIR 104) were less than expected. Risk for mesothelioma showed a sharp risk gradient with duration of exposure, increasing from 1 per 625 for those employed less than 2 years to 1 per 4.5 workers employed over 30 years. The ratio of mesothelioma to excess lung cancer cases was 2.9 to 1, or 3.6 to 1, if pleural cases of unspecified origin were included; the pleura to peritoneum ratio of verified mesothelioma cases was 20 to 1. This atypically high ratio of mesothelioma to excess lung cancer cases is suggested to be the combined result of high past asbestos exposures in the workers and their low prior risk for lung cancer, and possibly, relatively early smoking cessation in relation to asbestos exposure.}, } @article {pmid9874447, year = {1998}, author = {Plas, E and Riedl, CR and Pflüger, H}, title = {Malignant mesothelioma of the tunica vaginalis testis: review of the literature and assessment of prognostic parameters.}, journal = {Cancer}, volume = {83}, number = {12}, pages = {2437-2446}, doi = {10.1002/(sici)1097-0142(19981215)83:12<2437::aid-cncr6>3.0.co;2-g}, pmid = {9874447}, issn = {0008-543X}, mesh = {Adolescent ; Analysis of Variance ; Combined Modality Therapy ; Diagnosis, Differential ; Humans ; Male ; *Mesothelioma/etiology/pathology/therapy ; Neoplasm Invasiveness ; Prognosis ; Testicular Hydrocele/pathology ; *Testicular Neoplasms/etiology/pathology/therapy ; Testis/pathology ; }, abstract = {BACKGROUND: Only 73 cases of malignant mesothelioma of the tunica vaginalis testis have been reported in the last 30 years. Although these tumors were most often seen in patients between ages 55 and 75 years, 10% of the patients were younger than 25 years. Because prognostic parameters have not yet been reported, the authors present another case of a male age 14 years and a review of the available literature, which they conducted to determine prognostic parameters.

METHODS: The medical literature about malignant mesothelioma of the tunica vaginalis testis was reviewed. For the determination of prognostic parameters, a univariate and multivariate Cox regression model was used to assess the relevance of the patient's age, history of asbestos exposure, tumor histology, primary therapeutic approach, and presence of metastatic disease to survival.

RESULTS: Previous exposure to asbestos or asbestos-containing materials must be considered a risk factor for the development of malignant mesothelioma. The major difficulty in managing patients with malignant mesothelioma of the tunica vaginalis testis was determining an accurate preoperative diagnosis, which was reported in only two cases. Due to the lack of characteristic symptoms, 97.3% of the cases were diagnosed intraoperatively. Of patients who underwent local resection of the hydrocele wall, 35.7% experienced local tumor recurrence, as compared with 10.5% after scrotal orchiectomy and 11.5% after inguinal orchiectomy. Therefore, radical orchiectomy should be the first-line therapy. The median survival of the patients was 23 months, which decreased to 14 months in cases of recurrence. The overall recurrence rate (local and disseminated) was 52.5%. More than 60% of recurrences developed within the first 2 years of the follow-up. In some cases of disseminated mesothelioma, adjuvant chemotherapy or radiotherapy was given. Although reports on adjuvant treatments were limited, radiotherapy appeared to be more effective than chemotherapy. However, 37.9% died of disease progression. Assessment of prognostic parameters revealed a significant correlation of patient's age with survival (P < 0.01), with a better outcome for younger patients and a worse disease course for patients with primary disseminated disease (P < 0.05) in univariate analysis. A multivariate Cox regression model of prognostic parameters concerning survival did not yield statistically significant results.

CONCLUSIONS: Malignant mesotheliomas of the tunica vaginalis testis rarely occur, but the possibility should be considered for all age groups. Univariate analysis determined that a patient's age and the presence of primary disseminated disease were prognostic parameters related to survival. Due to the invasive potential of this disease and the risk of tumor recurrence, radical orchiectomy and close follow-up are strongly recommended.}, } @article {pmid9870144, year = {1998}, author = {Nicholson, AG and Goldstraw, P and Fisher, C}, title = {Synovial sarcoma of the pleura and its differentiation from other primary pleural tumours: a clinicopathological and immunohistochemical review of three cases.}, journal = {Histopathology}, volume = {33}, number = {6}, pages = {508-513}, doi = {10.1046/j.1365-2559.1998.00565.x}, pmid = {9870144}, issn = {0309-0167}, mesh = {Adult ; Biomarkers, Tumor/metabolism ; Diagnosis, Differential ; Fatal Outcome ; Humans ; Immunohistochemistry ; Male ; Pleural Neoplasms/metabolism/*pathology ; Sarcoma, Synovial/metabolism/*pathology ; }, abstract = {AIMS: Synovial sarcomas are rare tumours occasionally arising in the pleural cavity, a site where their histological characteristics may be mistaken for those of malignant mesothelioma. We examined three cases of primary pleural synovial sarcoma in order to look for clinicopathological features that may help in distinguishing them from both mesotheliomas and other sarcomas that may arise in the pleura.

METHODS AND RESULTS: All three patients were male, aged 42, 28 and 42, respectively, and had no known exposure to asbestos. One biphasic tumour contained neutral mucin in focal epithelial elements that also stained positively for BerEP4 and AUA1. All three tumours showed focal positivity for either keratin or EMA in the sarcomatous elements, and they also stained positively for bcl-2 protein and MIC2 gene product (CD99).

CONCLUSIONS: Our results emphasize the importance of being aware of synovial sarcoma as a possible primary pleural malignancy, especially in a young patient with a localized mass. In addition, the presence of bcl-2 protein perhaps represents a useful marker in distinguishing synovial sarcoma, especially monophasic variants, from mesothelioma within a panel of antibodies.}, } @article {pmid9869311, year = {1998}, author = {Hiraoka, T and Ohkura, M and Morinaga, K and Kohyama, N and Shimazu, K and Ando, M}, title = {Anthophyllite exposure and endemic pleural plaques in Kumamoto, Japan.}, journal = {Scandinavian journal of work, environment & health}, volume = {24}, number = {5}, pages = {392-397}, doi = {10.5271/sjweh.360}, pmid = {9869311}, issn = {0355-3140}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Air Pollutants/adverse effects/isolation & purification ; Asbestos/*adverse effects/isolation & purification ; Environmental Exposure/*adverse effects ; Female ; Humans ; Japan/epidemiology ; Lung Neoplasms/mortality ; Male ; Middle Aged ; Pleural Diseases/diagnostic imaging/*epidemiology/*etiology ; Prevalence ; Radiography ; }, abstract = {OBJECTIVES: This study explored the high prevalence of pleural plaques in the town of Matsubase in Kumamoto, Japan.

METHODS: Small-size chest X-ray film was used for screening, and all persons with pleural plaques were confirmed by computed tomography (CT). The prevalence rate of pleural plaques in the 4 districts of Matsubase and its surrounding towns and cities were also examined. The age-adjusted mortality rate for lung cancer in this town was compared with that of its surrounding towns and cities.

RESULTS: Pleural plaques were found in 1357 persons (724 men and 633 women) among the inhabitants who were more than 20 years of age in Matsubase between 1988 and 1993. CT scans ascertained 938 cases with pleural plaques among the 11 14 persons who participated. Thus at least 9.5% of the inhabitants over 20 years of age in this town had pleural plaques. The neighboring towns had a higher rate than the more distant towns. A large-scale open-cast asbestos mine and mill had been in operation in Matsubase between 1883 and 1970. Mineral analysis revealed anthophyllite fibers. Most of the plaques were found in persons who had never worked in the mine or mill.

CONCLUSIONS: The high prevalence of pleural plaques in Matsubase was due to anthophyllite exposure, mainly environmental. No mesotheliomas were found, however. These findings agree with those from an earlier study from Finland.}, } @article {pmid9869119, year = {1998}, author = {Karakoca, Y and Emri, S and Bagci, T and Demir, A and Erdem, Y and Baris, E and Sahin, AA}, title = {Environmentally-induced malignant pleural mesothelioma and HLA distribution in Turkey.}, journal = {The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease}, volume = {2}, number = {12}, pages = {1017-1022}, pmid = {9869119}, issn = {1027-3719}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos ; Case-Control Studies ; *Environmental Exposure ; Female ; *HLA Antigens ; Humans ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Pleural Neoplasms/*epidemiology/etiology ; Seroepidemiologic Studies ; Turkey/epidemiology ; Zeolites ; }, abstract = {SETTING: A large university hospital in Ankara, Turkey.

OBJECTIVE: To investigate the potential links, if any, between the occurrence of malignant pleural mesothelioma (MPM) and the presence and distribution of human leukocyte antigens (HLA) in patients environmentally exposed to asbestos and erionite in rural Anatolia, Turkey.

DESIGN: A case-control study design was used to compare the relative frequency and distribution of HLA among 31 MPM patients originating from the fibrous zeolite (erionite) and asbestos villages in central Anatolia, and two sets of controls. The cases represented all of the MPM cases diagnosed between 1995 and 1997 in our clinic at the Hacettepe University Hospital. One control group of 119 healthy individuals was drawn from Tuzköy, which has the largest population of three erionite villages, a very high prevalence of mesothelioma due to environmental exposure to erionite, and accounted for 16 of the MPM cases in the study. A second control group composed of 118 renal transplant donors was formed for external comparison.

RESULTS: A significant relation was found with the HLA-B41 antigen in 19.4% of the patients compared to 0.8% of the Tuzköy inhabitants (odds ratio [OR] 28.3; 95% confidence interval [CI] 3.1-652.5) and 1.7% of the referent renal donor population (OR 13.9; 95% CI 2.3-106.7). The frequency of the HLA-B58 and -DR16 antigens was also observed to be significantly higher in patients with MPM compared to the two control groups. The odds ratios of MPM in those with HLA-B58 were 8.6 (95% CI 1.2-72.4) and 8.5 (95% CI 1.2-71.8), respectively, compared to those of the Tuzköy inhabitants and renal donors.

CONCLUSION: The predictive role of the HLA antigens -B41, -B58 and -DR16 for MPM needs to be further investigated. This will help in screening the population at risk, and facilitate preventive measures such as family counselling and gene therapy.}, } @article {pmid9863397, year = {1998}, author = {Dagović, A and Jeremić, B}, title = {[Modern approach to malignant pleural mesothelioma. 1) Pretherapeutic evaluation].}, journal = {Srpski arhiv za celokupno lekarstvo}, volume = {126}, number = {7-8}, pages = {290-294}, pmid = {9863397}, issn = {0370-8179}, mesh = {Humans ; Mesothelioma/*diagnosis/therapy ; Pleural Neoplasms/*diagnosis/therapy ; }, abstract = {In this review we outlined the basis of current concepts of pretreatment evaluation in patients with malignant pleural mesothelioma. This tumour, rarely reported until sixties, is mostly connected with exposure to asbestos. Its increased incidence of approximately 50% is noted in last decades. Various histological types of this tumour are well known, but its biology is not well understood. Recent TNM classification and modern diagnostic approach such as computerized tomography and thoracoscopy, as well as standard means of diagnosis are aimed at obtaining early diagnosis and staging in order to undertake the adequate therapy.}, } @article {pmid9861481, year = {1998}, author = {Liu, BC and Fu, DC and Miao, Q and Wang, HH and You, BR}, title = {p53 gene mutations in asbestos associated cancers.}, journal = {Biomedical and environmental sciences : BES}, volume = {11}, number = {3}, pages = {226-232}, pmid = {9861481}, issn = {0895-3988}, mesh = {Adenocarcinoma/chemically induced/*genetics ; Adult ; Amino Acid Sequence ; Asbestos/*adverse effects ; Carcinoma, Adenosquamous/chemically induced/*genetics ; Carcinoma, Squamous Cell/chemically induced/*genetics ; DNA, Neoplasm/*genetics ; *Genes, p53 ; Humans ; Immunohistochemistry ; Lung Neoplasms/chemically induced/*genetics ; Lymphoma/chemically induced/*genetics ; Mesothelioma/chemically induced/*genetics ; Molecular Sequence Data ; *Point Mutation ; }, abstract = {The accumulation of mutant p53 protein in cancer cells was observed by immunohistochemistry analysis. DNA was extracted from paraffin-embedded tissue. Exons 5, 7 and 8 were amplified and studied by PCR-SSCP and sequencing analysis. Ten cases of asbestos associated cancer tissue were studied, of which five cases had adenocarcinoma, and the other five had mesothelioma, squamous carcinoma, small cell lung cancer, adenosquamous carcinoma and malignant lymphoma respectively. Employing monoclonal antibody PAb1801, five cases were found to be mutant p53 protein positive. Seven cases were found to have mutations by PCR-SSCP. A total of 7 cases (8 mutations) were found to be positive and 4 cases were found to be positive by both of these analyses. Of the 8 mutations found by SSCP analysis, 4(50%, 4/8) were clustered in exon 8. A high mutation frequency was noticed in adenocarcinoma (80%, 4/5). Sequencing analysis on two specimens revealed two hotspot mutations. In codon 234, TAC for tyrosin was mutated to AAC for asparagine by a T to A transversion of the first letter. In codon 273, CGT for arginine was mutated to AGT for serine by a C to A transversion of the first letter. In conclusion, the mutation of p53 gene is common in asbestos associated cancers. However, the mutational spectrum of asbestos associated cancers might be different from that of non-asbestos associated cancers.}, } @article {pmid9858688, year = {1999}, author = {Takeuchi, T and Nakajima, M and Morimoto, K}, title = {A human cell system for detecting asbestos cytogenotoxicity in vitro.}, journal = {Mutation research}, volume = {438}, number = {1}, pages = {63-70}, doi = {10.1016/s1383-5718(98)00163-6}, pmid = {9858688}, issn = {0027-5107}, mesh = {8-Hydroxy-2'-Deoxyguanosine ; Asbestos/toxicity ; Asbestos, Crocidolite/*toxicity ; Cell Division/*drug effects ; Deoxyguanosine/analogs & derivatives/metabolism ; Humans ; Mesothelioma/genetics ; Microscopy, Confocal ; *Mutagenicity Tests ; Mutagens/*toxicity ; Neutrophils/drug effects ; Phagocytosis/*drug effects ; Tumor Cells, Cultured ; }, abstract = {Crocidolite, a carcinogenic asbestos in humans, specifically induces mesothelioma. We investigated the cytogenotoxic effects of crocidolite in a human mesothelioma cell line, MSTO211H, and a human promyelocytic leukemia cell line, HL60. Using confocal laser scanning microscopy, we found that the MSTO211H cells had phagocytotic activity, whereas the HL60 cells did not. In the MSTO211H cells, crocidolite decreased the cell population and increased the numbers of polynucleated cells (PN) and tetraploid cells, and increased the coefficients of variation (CV) of DNA contents in G0/G1 cells and the formation of 8-hydroxydeoxyguanosine. In contrast, crocidolite showed none of these cytogenotoxic effects in HL60 cells. To investigate the importance of phagocytosis in the cytogenotoxicity of crocidolite, we sorted the crocidolite-phagocytosed cells from less-phagocytosed cells by fluorescence-activated cell sorting, and studied the differences in cytogenotoxicity between these two cell groups. We found significant increases in the numbers of PN and tetraploid cells and the CV in the crocidolite-phagocytosed cells compared to the less-phagocytosed cells. These findings indicate that MSTO211H cells are susceptible to the cytogenotoxic effects of asbestos due to their phagocytotic activity, and that the MSTO211H cell line is suitable for the detection of such effects on human cells by asbestos and other materials which need to be phagocytosed to exert their toxicity.}, } @article {pmid9849544, year = {1998}, author = {Gehanno, JF and Paris, C and Thirion, B and Caillard, JF}, title = {Assessment of bibliographic databases performance in information retrieval for occupational and environmental toxicology.}, journal = {Occupational and environmental medicine}, volume = {55}, number = {8}, pages = {562-566}, pmid = {9849544}, issn = {1351-0711}, mesh = {Asbestos ; Databases, Bibliographic/*standards ; Evaluation Studies as Topic ; Humans ; Latex Hypersensitivity ; MEDLINE ; Mesothelioma ; *Toxicology ; }, abstract = {OBJECTIVE: To determine the efficiency of the major bibliographic databases by assessing the percentage of references among the total literature available that can be retrieved from each database. We also evaluated the best database combinations to carry out an exhaustive search.

METHODS: BIOSIS, EMBASE, MEDLINE, NIOSH-TIC, and TOXLINE were searched on two topics: allergy to latex and asbestos and mesothelioma, in the title, abstract, or keywords (textwords). This search was performed for the years 1994 and 1995. All the records were classified by journal and author's name and were verified for each record whether or not it was indexed in each database. Statistical analysis was performed with chi 2 test.

RESULTS: 777 articles in 510 issues were found. The efficiency of each database (percentage of articles recovered) and of combinations varied between 11% and 63% for one database and between 42% and 86% for a combination of two databases. The reasons why these differences exist between databases, and within a database, between two different subjects or two different years are reported.

CONCLUSION: Firstly, it is not advisable to assert that a bibliography is complete when only one database is searched. Secondly, the efficiency of the databases may be quite different. Finally, it is suggested that the best way to be as exhaustive as possible is to search two or more databases-for example, in EMBASE and TOXLINE, or to a lesser extent EMBASE and MEDLINE. This seems to be the best compromise solution between time consumed for searching and efficiency.}, } @article {pmid9845725, year = {1998}, author = {Koss, MN and Fleming, M and Przygodzki, RM and Sherrod, A and Travis, W and Hochholzer, L}, title = {Adenocarcinoma simulating mesothelioma: a clinicopathologic and immunohistochemical study of 29 cases.}, journal = {Annals of diagnostic pathology}, volume = {2}, number = {2}, pages = {93-102}, doi = {10.1016/s1092-9134(98)80045-2}, pmid = {9845725}, issn = {1092-9134}, mesh = {Adenocarcinoma/drug therapy/*pathology/radiotherapy ; Adenocarcinoma, Bronchiolo-Alveolar/pathology ; Adult ; Aged ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; Lung Neoplasms/drug therapy/*pathology/radiotherapy ; Male ; Mesothelioma/drug therapy/*pathology/radiotherapy ; Middle Aged ; Staining and Labeling ; }, abstract = {We report 29 cases of adenocarcinomas whose clinical, gross, and microscopic appearance resembled diffuse malignant pleural mesothelioma. Initial criteria for inclusion in the study included availability of an open pleural biopsy or decortication specimen and microscopic evidence of neutral (periodic acid-Schiff positive) mucin in the tumor. The median age of the patients was 63 years (range, 31 to 78 years), with a peak age in the seventh decade. There were 24 men and five women. Thirteen of them had a history of smoking; six (21%) had possible or definite occupational exposure to asbestos. Three (21%) of 14 lung specimens showed ferruginous bodies and two (14%) showed microscopic evidence of asbestosis. At least 25 patients had pleural effusion, most typically unilateral. Needle biopsy of pleura showed malignancy in 10 (77%) of 13 cases. Most (20 of 29) patients underwent pleural stripping. Radiotherapy and chemotherapy was each given to three patients without effect. Median survival by Kaplan-Meier estimate was 8 months, with an 18-month survival of 13%. Histologically, glands (23 cases), nests (13 cases), tubulopapillary arrays (12 cases), or sheets (eight cases) of tumor cells were found. Spindling of neoplastic cells was seen in 10% of cases. Three (21%) of 14 lung specimens showed a subpleural adenocarcinoma. Antibodies to polyclonal CEA, Ber-EP4, Leu-M1, and B72.3 were positive in 94%, 56%, 50%, and 44% of cases, respectively. All but one of the cases stained with two or more of the antibodies CEA, Ber-EP4, Leu-M1, or B72.3. This study indicates that adenocarcinomas simulating mesothelioma are aggressive variants of peripheral adenocarcinomas with a poor prognosis, that they can show pathological evidence of asbestos exposure in a subset of cases, and that immunohistochemical and histochemical stains are useful in their differential diagnosis with diffuse malignant mesotheliomas.}, } @article {pmid9844455, year = {1998}, author = {Montero Martínez, C and Yebra Pimentel, MT and Bouso Montero, M and Blanco Aparicio, M and Veres Racaamonde, A and Otero González, I and Verea Hernando, H}, title = {[Malignant diffuse mesothelioma: contribution of 23 cases].}, journal = {Revista clinica espanola}, volume = {198}, number = {10}, pages = {665-668}, pmid = {9844455}, issn = {0014-2565}, mesh = {Female ; Humans ; Immunohistochemistry ; Male ; Mesothelioma/*diagnosis/etiology ; Middle Aged ; Pleural Neoplasms/*diagnosis/etiology ; Retrospective Studies ; Tomography, X-Ray Computed ; }, abstract = {Malignant diffuse mesothelioma is a tumour related to asbestos exposure, more common in males and located primarily in the chest cavity. Its diagnosis requires ruling out other tumours with pleural or peritoneal metastases, a biopsy showing a morphological pattern consistent with mesothelioma and in many cases to perform immunohistochemical markers to rule out an adenocarcinoma. We report here 20 cases of diffuse pleural mesothelioma and three cases of peritoneal mesothelioma in 20 males and three cases of peritoneal mesothelioma in 20 males and three females. Asbestos exposure was observed for 31% of cases. The most common clinical manifestations included headache and dyspnea; interestingly, three cases had hydropneumothorax with poor response to drainage. The diagnostic confirmation was obtained mainly with thoracotomy or laparoscopy biopsies and to rule out an adenocarcinoma immunohistochemical stainings were performed.}, } @article {pmid9844389, year = {1998}, author = {Okamoto, T and Yokota, S and Shinkawa, K and Kimura, H and Nishino, K and Ito, M and Ogura, T and Hanada, M}, title = {[Pleural malignant mesothelioma with osseous cartilaginous and rhabdomyogenic differentiation].}, journal = {Nihon Kokyuki Gakkai zasshi = the journal of the Japanese Respiratory Society}, volume = {36}, number = {8}, pages = {696-701}, pmid = {9844389}, issn = {1343-3490}, mesh = {Asbestosis/complications ; Bone and Bones/*pathology ; Cartilage/*pathology ; Cell Differentiation ; Humans ; Male ; Mesothelioma/*pathology ; Middle Aged ; Muscles/*pathology ; Pleural Neoplasms/*pathology ; }, abstract = {A 63-year-old man, who was formerly an asbestos factory worker who had been followed due to asbestosis, and was admitted to our hospital with left chest pain and dyspnea on exertion. A chest X-ray and chest computed tomogram (CT) on admission revealed a large tumor in the left lung field. Percutaneous needle biopsy determined that the tumor was a sarcoma. No clinical response was obtained by systemic chemotherapy. The autopsy revealed diffuse malignant mesothelioma of sarcomatous type with osseous, cartilaginous and rhabdomyogenic differentiation. Osseous and cartilaginous differentiation in a malignant mesothelioma is rare, and the presence of a malignant rhabdomyogenic component is the first to be described in the Japanese literature.}, } @article {pmid9828278, year = {1998}, author = {Liu, CC and Hsu, WH and Li, WY and Huang, MH}, title = {Treatment results of 17 patients with diffuse pleural mesothelioma.}, journal = {Annals of thoracic and cardiovascular surgery : official journal of the Association of Thoracic and Cardiovascular Surgeons of Asia}, volume = {4}, number = {5}, pages = {233-239}, pmid = {9828278}, issn = {1341-1098}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Male ; Mesothelioma/diagnosis/mortality/*therapy ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Pleural Neoplasms/diagnosis/mortality/*therapy ; Retrospective Studies ; Survival Rate ; }, abstract = {Treatment for diffuse pleural mesothelioma is very difficult. A retrospective study is established for analyzing the experiences in management of such a rare but fatal disease. From May 1960 to August 1996, 17 patients underwent treatment for pathologically confirmed malignant pleural mesothelioma at Veteran General Hospital-Taipei. The chart records were carefully reviewed and surgical specimens were reconfirmed by the pathologist. Single or combined treatment protocols with surgery, chemotherapy, and radiotherapy had been used according to the clinical situation. Pathological staging was recorded according to the Butchart staging system. Gender, smoking, asbestos exposure, histology, and survival were analyzed. There were 17 patients in total, including 15 males and 2 females with a mean age of 62 years. The most common symptoms were chest pain, cough, dyspnea and weight loss. For getting definite pathological diagnosis, the most sensitive procedures were video-assisted thoracic biopsy and open lung biopsy. In spite of trying multiple different treatment protocols, disease staging (p = 0.0186) and the epithelial pathological type (p = 0.0353) were the significant prognostic factors in our series. Prognosis of diffuse pleural mesothelioma is very poor. It was predominant in nen and no definite relationship with smoking or asbestos exposure was noted in our series, but it was relatively better in patients with early-stage and epithelial-type disease. Further efforts to improve the survival should be delivered on more aggressive cytoreductive surgery with early postoperative concurrent chemo-radiotherapy.}, } @article {pmid9819475, year = {1998}, author = {Algranti, E}, title = {Asbestos: current issues related to cancer and to uses in developing countries.}, journal = {Cadernos de saude publica}, volume = {14 Suppl 3}, number = {}, pages = {173-176}, doi = {10.1590/s0102-311x1998000700017}, pmid = {9819475}, issn = {0102-311X}, mesh = {Asbestos/*adverse effects ; Carcinogens/*adverse effects ; Carcinoma, Bronchogenic/*etiology ; *Developing Countries ; Environmental Exposure/adverse effects ; Humans ; Lung Neoplasms/*etiology ; Occupational Exposure/adverse effects ; Pulmonary Fibrosis/etiology ; }, abstract = {Asbestos is one of the main occupational carcinogens recognized and studied in the literature. Its uses have undergone major changes in recent decades, with severe restrictions on commercial amphiboles according to different patterns: in developed countries asbestos is strictly controlled or banned, except in Japan, while in developing countries consumption has leveled off or increased. As an example, Brazil is one the seven world leaders in asbestos production and consumption. Although there is a clear excess of mesotheliomas linked to amphibole exposure, mainly to crocidolite, there is no evidences that chrysotile is harmless to the pleura. Also, the relationship between fibrogenesis and carcinogenesis is not sufficiently understood to defend the concept that there are protective exposure limits to both diseases. "Controlled use" policy may be effective at the occupational level in a select group of companies, representing only a fraction of the exposed population. In developing countries subject to economic pressures, these issues merit proper discussion to avoid unnecessary disease and death.}, } @article {pmid9817178, year = {1998}, author = {Boutin, C and Schlesser, M and Frenay, C and Astoul, P}, title = {Malignant pleural mesothelioma.}, journal = {The European respiratory journal}, volume = {12}, number = {4}, pages = {972-981}, doi = {10.1183/09031936.98.12040972}, pmid = {9817178}, issn = {0903-1936}, mesh = {Asbestos/adverse effects ; Combined Modality Therapy ; Female ; Humans ; Immunotherapy ; Incidence ; Male ; Mesothelioma/*diagnosis/epidemiology/etiology/*therapy ; Pleural Neoplasms/*diagnosis/epidemiology/etiology/*therapy ; Prognosis ; Risk Factors ; Survival Rate ; }, abstract = {The incidence of malignant pleural mesothelioma (MPM) has risen for some decades and is expected to peak between 2010 and 2020. Up to now, no single treatment has been proven to be effective and death usually occurs within about 12-17 months after diagnosis. Perhaps because of this poor prognosis, early screening has incited little interest. However, certain forms may have a better prognosis when diagnosed early and treated by multimodal therapy or intrapleural immunotherapy. Diagnosis depends foremost on histological analysis of samples obtained by thoracoscopy. This procedure allows the best staging of the pleural cavity with an attempt to detect visceral pleural involvement, which is one of the most important prognostic factors. Although radiotherapy seems necessary and is efficient in preventing the malignant seeding after diagnostic procedures in patients, there has been no randomized phase III study showing the superiority of any treatment compared with another. However, for the early-stage disease (stage I) a logical therapeutic approach seems to be neoadjuvant intrapleural treatment using cytokines. For more advanced disease (stages II and III) resectability should be discussed with the thoracic surgeons and a multimodal treatment combining surgery, radiotherapy and chemotherapy should be proposed for a randomized controlled study. Palliative treatment is indicated for stage IV. In any case, each patient should be enrolled in a clinical trial.}, } @article {pmid9810152, year = {1998}, author = {McDonald, JC}, title = {Mineral fibre persistence and carcinogenicity.}, journal = {Industrial health}, volume = {36}, number = {4}, pages = {372-375}, doi = {10.2486/indhealth.36.372}, pmid = {9810152}, issn = {0019-8366}, mesh = {Biological Availability ; Humans ; Lung/chemistry ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Mineral Fibers/*adverse effects ; Mining ; *Occupational Health ; Research Design ; Risk Assessment ; }, abstract = {Epidemiological research during the past 40 years has demonstrated with increasing clarity that amphibole asbestos fibres--crocidolite, amosite and tremolite--are more carcinogenic than chrysotile. A smaller number of well-controlled studies using lung burden analyses, while adding to the specificity of this conclusion, have shown that amphibole fibres also differ from chrysotile in being far more durable and biopersistent in lung tissue. Analyses of mesothelioma and lung cancer in a large cohort of Canadian chrysotile miners and millers have recently shown that the low-level presence of fibrous tremolite in these mines, rather than the chrysotile, may well be responsible. The high risk of lung cancer, but not of mesothelioma, in the chrysotile textile industry remains anomalous and cannot be explained in this way. These various findings are directly relevant to the choice of the experimental methods which should be used for screening man-made fibres for industrial use. Although it is clear that biopersistence is a major determinant of cancer risk in animals, and perhaps also in man, other factors affecting the biological activity of mineral fibres may also be important.}, } @article {pmid9806392, year = {1998}, author = {Pass, HI and Donington, JS and Wu, P and Rizzo, P and Nishimura, M and Kennedy, R and Carbone, M}, title = {Human mesotheliomas contain the simian virus-40 regulatory region and large tumor antigen DNA sequences.}, journal = {The Journal of thoracic and cardiovascular surgery}, volume = {116}, number = {5}, pages = {854-859}, doi = {10.1016/S0022-5223(98)00438-3}, pmid = {9806392}, issn = {0022-5223}, mesh = {Animals ; Cohort Studies ; Cricetinae ; DNA, Viral/*genetics ; Gene Expression Regulation, Neoplastic/physiology ; Gene Expression Regulation, Viral/physiology ; Humans ; Mesothelioma/*virology ; Papillomavirus Infections/*virology ; Peritoneal Neoplasms/*virology ; Pleural Neoplasms/*virology ; Polymerase Chain Reaction ; Regulatory Sequences, Nucleic Acid/*genetics ; Simian virus 40/*genetics ; Tumor Virus Infections/*virology ; Virus Replication/genetics ; }, abstract = {BACKGROUND: A cohort (20%) of patients with mesothelioma will not have an exposure to asbestos. Recently, a DNA tumor virus (simian virus 40) has been shown to cause hamster mesotheliomas; we previously described simian virus 40-like DNA amino terminus sequences in 29 of 48 mesotheliomas. We analyzed an additional 42 mesotheliomas to determine (1) whether our initial observations were durable and (2) the extent to which the simian virus 40 genome is present in mesotheliomas.

METHODS: Genomic DNA was extracted from snap frozen mesothelioma tumor samples and from the simian virus 40-induced hamster mesothelioma tumor H9A. Polymerase chain reaction primers were used to amplify various simian virus 40 large T-antigen regions including a 105-base pair amino terminus fragment, a 281-base pair carboxyl terminus fragment, and a 310-base pair fragment of the enhancer promoter region. Endonuclease digestions and Southern blotting were used to verify the expected product.

RESULTS: Thirty of the 42 (71%) samples amplified T-antigen amino sequences, and specificity was verified by Southern hybridization. Sixteen of 42 samples (38%) amplified the appropriate size fragment for the carboxyl terminus, and digestion with BsaB1 matched that of H9A. Twenty-two of 42 samples (52%) amplified simian virus 40 regulatory sequences and Fok1 digestion matched that of the hamster control tumor. Sequence analysis (4 patients) revealed 100% homology with the regulatory region of simian virus 40 strain 776.

CONCLUSIONS: These data suggest an association between the simian virus 40 virus and human mesothelioma that could be exploited for diagnostic/therapeutic options including early detection and potential vaccination strategies.}, } @article {pmid9805972, year = {1998}, author = {De Vuyst, P}, title = {[Asbestos: current knowledge and perspectives].}, journal = {Revue medicale de Bruxelles}, volume = {19}, number = {4}, pages = {A351-4}, pmid = {9805972}, issn = {0035-3639}, mesh = {Asbestosis/*complications/*diagnosis/epidemiology/prevention & control ; Cause of Death ; Clinical Competence ; Humans ; Neoplasms/etiology ; Occupational Medicine/education ; }, abstract = {Diseases due to asbestos inhalation are not only a concern for occupational physicians, but also for general practicioners and pneumologists. The real or supposed risk has extended beyond the factories employing "primary asbestos workers" to thousands of people exposed to this material or simply working in buildings insulated with asbestos. The spectrum of asbestos-related diseases has changed: asbestosis (parenchymal fibrosis due to asbestos) tends to disappear, whereas the incidence of pleural lesions, which can be associated with lower cumulative exposures, increases. Patients with asbestos related diseases do not die any more from respiratory failure but from late neoplastic complications, such as mesothelioma and lung cancer. The lack of interest and of training in occupational medicine leads to an underrecognition and an underestimation of cancers due to asbestos by the physicians. Recent progresses in CT imaging and evaluations of exposure to fibers through mineralogical analysis of lung samples have led to improve the diagnostic approach of fiber-related diseases.}, } @article {pmid9797750, year = {1998}, author = {Williams, T and Slade, P and Raeburn, J}, title = {Lump sum compensation for asbestos related lung disease.}, journal = {Thorax}, volume = {53}, number = {7}, pages = {535}, pmid = {9797750}, issn = {0040-6376}, mesh = {Asbestosis/*complications ; Humans ; Lung Neoplasms ; Mesothelioma ; Pleural Diseases ; United Kingdom ; Workers' Compensation/*legislation & jurisprudence ; }, } @article {pmid9789373, year = {1998}, author = {Merler, E and Piffer, S}, title = {[A thorough study of mesothelioma cases. The role of the National Health Service statistics].}, journal = {Epidemiologia e prevenzione}, volume = {22}, number = {2}, pages = {65-66}, pmid = {9789373}, issn = {1120-9763}, mesh = {Asbestos/*adverse effects ; Humans ; Italy/epidemiology ; Mesothelioma/*epidemiology/etiology ; National Health Programs ; Occupational Diseases/*epidemiology/etiology ; Pleural Neoplasms/*epidemiology/etiology ; *Registries ; Statistics as Topic ; }, } @article {pmid9788590, year = {1998}, author = {Testa, JR and Carbone, M and Hirvonen, A and Khalili, K and Krynska, B and Linnainmaa, K and Pooley, FD and Rizzo, P and Rusch, V and Xiao, GH}, title = {A multi-institutional study confirms the presence and expression of simian virus 40 in human malignant mesotheliomas.}, journal = {Cancer research}, volume = {58}, number = {20}, pages = {4505-4509}, pmid = {9788590}, issn = {0008-5472}, support = {CA 45745/CA/NCI NIH HHS/United States ; CA 74283/CA/NCI NIH HHS/United States ; P01 NS36466/NS/NINDS NIH HHS/United States ; }, mesh = {Asbestos/toxicity ; Base Sequence ; Cocarcinogenesis ; DNA, Viral/analysis ; Humans ; Mesothelioma/etiology/*virology ; Molecular Sequence Data ; Polymerase Chain Reaction ; Simian virus 40/*isolation & purification ; }, abstract = {Exposure to the carcinogen asbestos is a major factor in the development of malignant mesothelioma. However, not all mesotheliomas are associated with asbestos exposure, and only a small minority of people exposed to asbestos develop mesothelioma. Therefore, the identification of the cofactors that render certain individuals more susceptible to asbestos or that cause mesothelioma in people not exposed to asbestos has been a major priority of the International Mesothelioma Interest Group. The possible association of SV40 with mesothelioma was recently discussed in a special session at the Fourth International Mesothelioma Interest Group Conference, and it was decided to conduct a multi-institutional study to independently verify the presence of this tumor virus in mesotheliomas. We report the results of this investigation: (a) DNA and protein analyses revealed SV40 sequences and SV40 large T antigen expression in 10 of 12 mesotheliomas tested (83%); and (b) electron microscopy demonstrated variable amounts of asbestos fibers in 5 (71%) of 7 corresponding lung tissues available for analysis. Our results demonstrate that SV40 DNA is frequently present and expressed in mesotheliomas in the United States. Because our data demonstrate that some patients test positive for both SV40 and asbestos, the possibility that these two carcinogens interact should be investigated in future studies.}, } @article {pmid9781187, year = {1998}, author = {Ameille, J}, title = {[Risk and clinical surveillance of workers exposed to asbestos].}, journal = {La Revue du praticien}, volume = {48}, number = {12}, pages = {1299-1302}, pmid = {9781187}, issn = {0035-2640}, mesh = {Asbestos/*adverse effects ; Asbestosis/*prevention & control/therapy ; Family Practice ; Humans ; Occupational Exposure/*adverse effects ; Population Surveillance ; Retirement ; }, abstract = {The role of the family doctor in the medical surveillance of asbestos-exposed workers is important, mainly after retirement. The surveillance modalities should take into account the levels of exposure and the date of the beginning of exposure (long latency period of asbestos-related diseases). Due to the lack of evidence of improvement of lung cancer prognosis, and in the absence of effective treatment of mesothelioma, the interest of medical surveillance is at the present time medico-legal rather than strictly medical. Consequently, maximalist attitudes, costly and may be hazardous, should be avoided.}, } @article {pmid9781186, year = {1998}, author = {Paris, C and Chevreau, L and Letourneux, M}, title = {[Asbestos-related diseases].}, journal = {La Revue du praticien}, volume = {48}, number = {12}, pages = {1292-1297}, pmid = {9781186}, issn = {0035-2640}, mesh = {*Asbestosis/complications/diagnostic imaging/epidemiology/etiology ; Humans ; Lung Neoplasms/epidemiology/*etiology ; Mesothelioma/epidemiology/*etiology ; Radiography ; }, abstract = {The growing use of asbestos in France like in other industrialized countries since the beginning of the century is the reason of the increase of asbestos-related diseases, which occur after long latency periods. From asymptomatic benign pleural plaques up to malignant mesothelioma of poor prognosis, the fibrogenic and carcinogenic properties of asbestos mainly concern occupationally exposed subjects. The Institut national de la santé et de la recherche médicale (INSERM) expert committee concluded that about 1,950 deaths due to asbestos-related cancers occurred in France in 1996. Reinforcement of French legislation aims at reducing all kinds of asbestos exposure.}, } @article {pmid9776236, year = {1998}, author = {Galateau-Salle, F and Bidet, P and Iwatsubo, Y and Gennetay, E and Renier, A and Letourneux, M and Pairon, JC and Moritz, S and Brochard, P and Jaurand, MC and Freymuth, F}, title = {Detection of SV40-like DNA sequences in pleural mesothelioma, bronchopulmonary carcinoma and other pulmonary diseases.}, journal = {Developments in biological standardization}, volume = {94}, number = {}, pages = {147-152}, pmid = {9776236}, issn = {0301-5149}, mesh = {Antigens, Polyomavirus Transforming/genetics ; DNA, Viral/*analysis ; Humans ; Lung Diseases/*virology ; Lung Neoplasms/virology ; Mesothelioma/*virology ; Pleural Neoplasms/*virology ; Polymerase Chain Reaction ; Simian virus 40/genetics/*isolation & purification ; }, abstract = {Mesotheliomas are pleural-based tumours mainly associated with asbestos exposure (70% of cases) and the incidence is still raising. Recently, a possible viral connection was reported and 60% of mesotheliomas were demonstrated to contain and express SV40-like DNA sequences. In this study, the presence of SV40-like DNA sequences were investigated in mesotheliomas (15 tissue samples and six cell lines) and in 63 additional bronchopulmonary carcinomas, one parietal osteosarcoma and non-malignant lung samples as well as in organizing pleuritis (8). Finally, 163 samples were analysed by the polymerase chain reaction (PCR) with a set of primers PYV.for and PYV.rev to amplify a 173 bp region of the SV40 Tag. and a 179 bp region JC virus (JCV) as well as a 182 bp region BK virus (BKV). PCR amplification and hybridization with a probe specific for SV40 Tag revealed that 47.6% of mesotheliomas, 28.6% of primary bronchopulmonary carcinomas and 16% of non-neoplasic lung diseases contained SV40-like DNA sequences. No statistically significant difference in the occurrence of these DNA sequences was found between malignant mesothelioma and bronchopulmonary carcinoma. However, a significantly higher number of mesothelioma cases exhibited SV40- like DNA sequences in comparison with non-malignant pleural and pulmonary tissues. The DNA sequences were not related to BK and JC virus sequences. These results indicate that SV40-like DNA sequences are present in mesotheliomas as well as in bronchopulmonary carcinomas and non-malignant pleuropulmonary diseases.}, } @article {pmid9776225, year = {1998}, author = {Mutti, L and De Luca, A and Claudio, PP and Convertino, G and Carbone, M and Giordano, A}, title = {Simian virus 40-like DNA sequences and large-T antigen-retinoblastoma family protein pRb2/p130 interaction in human mesothelioma.}, journal = {Developments in biological standardization}, volume = {94}, number = {}, pages = {47-53}, pmid = {9776225}, issn = {0301-5149}, mesh = {Aged ; Antigens, Polyomavirus Transforming/*genetics/metabolism ; Asbestosis/complications/virology ; DNA, Viral/*chemistry ; Female ; Humans ; Lung Neoplasms/*genetics/virology ; Male ; Mesothelioma/genetics/*virology ; Middle Aged ; Papillomavirus Infections/*genetics/virology ; Phosphoproteins/*genetics/metabolism ; *Proteins ; Retinoblastoma Protein/*genetics/metabolism ; Retinoblastoma-Like Protein p130 ; Simian virus 40/*genetics ; Smoking ; Tumor Virus Infections/*genetics/virology ; }, abstract = {The oncoprotein of the Simian virus 40, SV40 large T-antigen (Tag), is reported to target and inactivate growth-suppressive proteins such as the retinoblastoma (Rb) family and p53 leading to transformation of human cell lines in vitro, to produce tumours in rodents, and to be detected in several human cancers including mesothelioma. In support of the potential role of SV40 Tag in the pathogenesis of certain human cancers, we have found SV40-like sequences in 8/25 bioptic specimens of mesothelioma from patients with exposure to asbestos fibres. We have also demonstrated that the SV40 Tag detected in human mesothelioma binds the retinoblastoma family protein pRb2/p130 in 5/5 specimens studied. We submit that the tumorigenic potential of SV40 Tag in some human mesotheliomas may arise from its ability to interact with and thereby inactivate several tumour and/or growth suppressive proteins in cooperation with asbestos fibres in inducing pleural mesothelioma.}, } @article {pmid9775184, year = {1998}, author = {Belange, G and Gompel, H and Chaouat, Y and Chaouat, D}, title = {[Malignant peritoneal mesothelioma occurring in periodic disease: apropos of a case].}, journal = {La Revue de medecine interne}, volume = {19}, number = {6}, pages = {427-430}, doi = {10.1016/s0248-8663(98)80867-9}, pmid = {9775184}, issn = {0248-8663}, mesh = {Abdominal Pain/pathology ; Ascites/drug therapy/pathology ; Colchicine/therapeutic use ; Familial Mediterranean Fever/drug therapy/*pathology ; Fatal Outcome ; Humans ; Male ; Mesothelioma/*pathology ; Middle Aged ; Peritoneal Diseases/*pathology ; Peritonitis/pathology ; Recurrence ; }, abstract = {INTRODUCTION: Peritoneal mesothelioma is a rare malignant neoplasm that might be linked to chronic peritoneal inflammation. As well, the association peritoneal mesothelioma-familial Mediterranean fever is uncommon.

EXEGESIS: We report the case of a 60-year-old man who presented for 30 years with standard periodic familial Mediterranean fever accompanied by acute abdominal episodes, sensitive to colchicine. Between 1988 and 1995, acute abdominal episodes were accompanied by more and more profuse recurrent ascites, partially resolving under colchicine treatment. In 1995, the last episode was severe (with loss of weight and inability to tolerate feeding) and conducted to the patient's death due to peritoneal mesothelioma, as confirmed by the biopsy.

CONCLUSION: Profuse and recurrent ascites is unusual in standard periodic familial Mediterranean fever. Asbestos exposure at the origin of peritoneal mesothelioma is not well documented. Furthermore, the disease clinical and paraclinical features are misleading, and the diagnosis is based on histology. The prognosis is severe, and treatment is usually disappointing. Our observation clearly demonstrates the interconnection between an unusual form of profuse and relapsing ascites that occurred in the course of a periodic disease and peritoneal mesothelioma. The potential role of recurrent peritonitis related to familial Mediterranean fever in the pathogenesis of the tumor is discussed.}, } @article {pmid9766991, year = {1998}, author = {Churg, A}, title = {Nonoccupational exposure to chrysotile asbestos and the risk of lung cancer.}, journal = {The New England journal of medicine}, volume = {339}, number = {14}, pages = {999; author reply 1001-2}, doi = {10.1056/NEJM199810013391412}, pmid = {9766991}, issn = {0028-4793}, mesh = {Asbestos, Amphibole/*analysis ; Asbestos, Serpentine/analysis ; Asbestosis/etiology ; Environmental Exposure/adverse effects ; Female ; Humans ; Lung/*chemistry ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Occupational Exposure/adverse effects ; Quebec ; }, } @article {pmid9766982, year = {1998}, author = {Case, BW}, title = {Nonoccupational exposure to chrysotile asbestos and the risk of lung cancer.}, journal = {The New England journal of medicine}, volume = {339}, number = {14}, pages = {1001; author reply 1002}, pmid = {9766982}, issn = {0028-4793}, mesh = {Asbestos, Serpentine/*adverse effects ; Environmental Exposure/adverse effects ; Female ; Humans ; Maximum Allowable Concentration ; Mesothelioma/*mortality ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*mortality ; Quebec/epidemiology ; }, } @article {pmid9766980, year = {1998}, author = {Sokas, RK}, title = {Nonoccupational exposure to chrysotile asbestos and the risk of lung cancer.}, journal = {The New England journal of medicine}, volume = {339}, number = {14}, pages = {1000; author reply 1001-2}, pmid = {9766980}, issn = {0028-4793}, mesh = {Asbestos, Serpentine/*adverse effects ; Asbestosis/mortality ; Environmental Exposure/*adverse effects ; Female ; Humans ; Lung Neoplasms/*epidemiology ; Mesothelioma/mortality ; Mortality ; Risk ; Smoking/epidemiology ; }, } @article {pmid9766909, year = {1998}, author = {Phoon, WO}, title = {Occupational health in Australia.}, journal = {International archives of occupational and environmental health}, volume = {71}, number = {6}, pages = {363-371}, doi = {10.1007/s004200050294}, pmid = {9766909}, issn = {0340-0131}, mesh = {Australia ; Government ; Health Priorities ; Humans ; *Occupational Health/legislation & jurisprudence/statistics & numerical data ; Occupational Health Services/*organization & administration ; Occupational Medicine/*education ; State Government ; Workers' Compensation/economics/trends ; }, abstract = {Australia is a developed country in the Asia-Pacific Region with a large land area but a small population. Its main economic activities are mining, agriculture and manufacturing, with its service and high-technology industries being the fastest growing sectors in recent years. The regulation and enforcement of Occupational Health and Safety policies are mainly administered by the Industrial Relations Departments of eight State and Territory jurisdictions in the country. A National Occupational Health and Safety Commission coordinates occupational health and safety at the Commonwealth level. In 1987 the six occupational health and safety priorities in Australia were listed as occupational back pain, management of chemicals used at work, occupational noise-induced hearing loss, occupational skin disorders, occupational cancer and mechanical equipment injury. Australia has probably the highest incidence of malignant mesothelioma in the world, although the use of asbestos has been largely phased out. There was an almost explosive "epidemic" of repetition strain injury in the 1980s. Approximately 500 work-related fatalities and 10,000 work-related injuries are notified for workers' compensation every year. In addition, it is estimated that there are several thousand cases of work-related diseases every year, many of which go unreported. Occupational physicians undergo 4 years of specialisation training. Occupational hygienists, nurses and ergonomists receive training supervised by their respective professional organisations.}, } @article {pmid9764109, year = {1998}, author = {Weiland, SK and Straif, K and Chambless, L and Werner, B and Mundt, KA and Bucher, A and Birk, T and Keil, U}, title = {Workplace risk factors for cancer in the German rubber industry: Part 1. Mortality from respiratory cancers.}, journal = {Occupational and environmental medicine}, volume = {55}, number = {5}, pages = {317-324}, pmid = {9764109}, issn = {1351-0711}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Cause of Death ; Cohort Studies ; Dust/adverse effects ; *Extraction and Processing Industry ; Follow-Up Studies ; Germany/epidemiology ; Humans ; Inhalation Exposure ; Laryngeal Neoplasms/etiology/*mortality ; Lung Neoplasms/etiology/*mortality ; Male ; Mesothelioma/mortality ; Middle Aged ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*mortality ; Risk Factors ; Rubber/*adverse effects ; Time Factors ; }, abstract = {OBJECTIVES: To determine the cancer specific mortality by work area among active and retired male workers in the German rubber industry.

METHODS: A cohort of 11,663 male German workers was followed up for mortality from 1 January 1981 to 31 December 1991. Cohort members were classified as active (n = 7536) or retired (n = 4127) as of 1 January 1981 and had been employed for at least one year in one of five study plants producing tyres or technical rubber goods. Work histories were reconstructed with routinely documented "cost centre codes" which were classified into six categories: I preparation of materials; II production of technical rubber goods; III production of tyres; IV storage and dispatch; V maintenance; and VI others. Standardised mortality ratios (SMRs) adjusted for age and calendar year and 95% confidence intervals (95% CIs), stratified by work area (employment in respective work area for at least one year) and time related variables (year of hire, lagged years of employment in work area), were calculated from national reference rates.

RESULTS: SMRs for laryngeal cancer were highest in work area I (SMR 253; 95% CI 93 to 551) and were significant among workers who were employed for > 10 years in this work area (SMR 330; 95% CI 107 to 779). Increased mortality rates from lung cancer were identified in work areas I (SMR 162; 95% CI 129 to 202), II (SMR 134; 95% CI 109 to 163), and V (SMR 131; 95% CI 102 to 167). Mortality from pleural cancer was increased in all six work areas, and significant excesses were found in work areas I (SMR 448; 95% CI 122 to 1146), II (SMR 505; 95% CI 202 to 1040), and V (SMR 554; 95% CI 179 to 1290).

CONCLUSION: A causal relation between the excess of pleural cancer and exposure to asbestos among rubber workers is plausible and likely. In this study, the pattern of excess of lung cancer parallels the pattern of excess of pleural cancer. This points to asbestos as one risk factor for the excess deaths from lung cancer among rubber workers. The study provides further evidence for an increased mortality from laryngeal cancer among workers in the rubber industry, particularly in work area I.}, } @article {pmid9754864, year = {1998}, author = {Boffetta, P and Burdorf, A and Goldberg, M and Merler, E and Siemiatycki, J}, title = {Towards the coordination of European research on the carcinogenic effects of asbestos.}, journal = {Scandinavian journal of work, environment & health}, volume = {24}, number = {4}, pages = {312-317}, pmid = {9754864}, issn = {0355-3140}, mesh = {Asbestos/*adverse effects ; Europe ; Humans ; *International Cooperation ; Lung Neoplasms/*etiology/prevention & control ; Mesothelioma/*etiology/prevention & control ; Occupational Diseases/*etiology/prevention & control ; Pleural Neoplasms/*etiology/prevention & control ; Population Surveillance ; Research ; Risk ; }, } @article {pmid9753899, year = {1998}, author = {Castleman, B and Dement, J and Giannasi, F and Frank, AL and Frumkin, H and Gochfeld, M and Goldstein, BD and Grandjean, P and LaDou, J and Lemen, RA and Levy, BS and Maltoni, C and McDiarmid, M and Silbergeld, EK and Teitelbaum, DT and Thebaud-Mony, A and Upton, AC and Wegman, DH}, title = {Salud ocupacional.}, journal = {International journal of occupational medicine and environmental health}, volume = {11}, number = {2}, pages = {195-197}, pmid = {9753899}, issn = {1232-1087}, mesh = {Argentina/epidemiology ; Asbestos/*adverse effects ; Asbestos, Serpentine/*adverse effects ; Carcinogens/*adverse effects ; Environmental Exposure/adverse effects ; Humans ; Incidence ; Journalism, Medical/standards ; Lung Neoplasms/*chemically induced/epidemiology ; Mesothelioma/*chemically induced/epidemiology ; Occupational Diseases/*chemically induced/epidemiology ; Risk Assessment ; }, } @article {pmid9753896, year = {1998}, author = {Szeszenia-Dabrowska, N and Wilczyńska, U and Szymczak, W and Laskowicz, K}, title = {Environmental exposure to asbestos in asbestos cement workers: a case of additional exposure from indiscriminate use of industrial wastes.}, journal = {International journal of occupational medicine and environmental health}, volume = {11}, number = {2}, pages = {171-177}, pmid = {9753896}, issn = {1232-1087}, mesh = {Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects/analysis ; *Cause of Death ; Cohort Studies ; Data Collection ; Environmental Monitoring ; Epidemiological Monitoring ; Female ; Humans ; Incidence ; Industrial Waste/*adverse effects ; Industry ; Lung Neoplasms/chemically induced/*epidemiology ; Male ; Mesothelioma/chemically induced/*epidemiology ; Middle Aged ; Occupational Exposure/*adverse effects/analysis ; Poland/epidemiology ; Risk Factors ; Sex Distribution ; Survival Rate ; }, abstract = {The paper presents data on cancer risk, especially pleural mesothelioma and lung cancer, among the workers of asbestos cement plant who living in the vicinity of the plant, were also environmentally exposed to asbestos. In 1959 an asbestos cement factory was founded in the rural area of south-eastern Poland. Apart from chrysotile asbestos, crocidolite was used till 1985 chiefly for the manufacture of pressure pipes. The blue asbestos made up 15% of the mean annual tonnage of the processed asbestos. It was found that soon after asbestos production had started the process wastes were made available to local community, particularly to the workers of that factory. For over twenty years asbestos wastes of all kinds, both wet (process sludge) and dry (from pipe and sheet grinding) were exploited for the hardening of roads, paths, farmyards and sports fields and as construction material components. For the evaluation of cancer risk due to occupational exposure to asbestos a cohort of 1,526 workers employed in this factory was observed till the end of 1996. The cohort availability was 95.6%. Standardized mortality ratio (SMR) was calculated using the man-years method. The reference population was the general population of Poland. The results of the study demonstrated a statistically significant increase in the risk of a) pleural mesothelioma--over an 80-fold excess among males and over a 200-fold one among females; b) lung cancer in females--over a 6-fold excess; c) colon cancer in males--over a 3-fold excess. In the 1990 ten new cases of pleural mesothelioma in the cohort were reported. As compared to other asbestos-cement cohorts in Poland, observed at the same time, this cohort presented a very high risk of pleural mesothelioma. The analysis of 16 cases of pleural mesothelioma found in the cohort from 1987 to 1997 revealed 4 cases with very short employment period (3.5 months-5 years) including two cases with relatively short latency period (11-12 years). In order to find explanation of these findings, additional investigations were made. The epidemiological study indicated that all these persons were at the same time subject to non-occupational exposure associated with massive utilization of commonly available asbestos-cement wastes as road surface material.}, } @article {pmid9752282, year = {1998}, author = {Ruffié, P and Lehmann, M and Galateau-Sallé, F and Lagrange, JL and Pairon, JC}, title = {[Standards, Options, and Recommendations for the management of patients with malignant mesothelioma of the pleura. Fédération Nationale des Centres de Lutte Contre le Cancer].}, journal = {Bulletin du cancer}, volume = {85}, number = {6}, pages = {545-561}, pmid = {9752282}, issn = {0007-4551}, mesh = {Humans ; *Mesothelioma/diagnosis/epidemiology/etiology/therapy ; Neoplasm Staging ; *Occupational Diseases/diagnosis/epidemiology/etiology/therapy ; *Pleural Neoplasms/diagnosis/epidemiology/etiology/therapy ; Prognosis ; }, abstract = {The "Standards, Options and Recommandations" (SOR), started in 1993, are a collaborative project between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcomes for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary experts group, with feedback from specialists in cancer care delivery. The objectives are to develop a clinical practice guideline with definitions of Standards. Options and Recommendations for the clinical care of malignant pleural mesothelioma. Data have been identified by literature search using Medline (1966-June 1997) and personal references lists. The main criteria considered were incidence, risk factors, pronostic factors and efficacy of cancer treatment. Once the guideline was defined, the document was submitted to 40 independent reviewers for peer review, and to the medical committees of the 20 French Cancer Centres for review and agreement. The results are: 1) systematic assessment of (professional) exposure to asbestos is based on a standardized interrogatory, completed by specific consultation for professional disease; 2) diagnostic and clinical staging is based on multiple biopsies under thoracoscopy and thoracic scanner; 3) there is no indication for extemporaneous examination, immunocytochemistry should use cytokeratine, EMA, vimentine, ACE, Leu-M1; 4) clinical care: the recommended staging classification is the IMIG (International Mesothelioma Interest Group) classification; 5) validated, independent pronostic factors are stage of disease patient's functional status and histologic type (i.e. epithelial lesions are of better prognosis); 6) treatment is based on symptomatic and palliative treatment options. Anticancer treatments (surgery, chemotherapy, immunotherapy, radiotherapy) did not show significant improvement of survival. The inclusion of patients in clinical trials is recommended.}, } @article {pmid9751275, year = {1998}, author = {Ascoli, V and Scalzo, CC and Bruno, C and Facciolo, F and Lopergolo, M and Granone, P and Nardi, F}, title = {Familial pleural malignant mesothelioma: clustering in three sisters and one cousin.}, journal = {Cancer letters}, volume = {130}, number = {1-2}, pages = {203-207}, doi = {10.1016/s0304-3835(98)00142-6}, pmid = {9751275}, issn = {0304-3835}, mesh = {Aged ; Family ; Female ; Food Handling ; Humans ; Male ; Mesothelioma/*genetics ; Middle Aged ; Occupational Diseases/genetics ; Pedigree ; Pleural Neoplasms/*genetics ; }, abstract = {Malignant mesothelioma is associated with asbestos, yet its occurrence in genetically-related individuals suggests a role of host predisposition. We have identified a cluster of pleural malignant mesothelioma in three sisters and one cousin (male). The women had worked in the same confectionery shop as pastry cooks and/or pastry shop assistants; the use of an asbestos-insulated oven was the putative source of exposure. The man had occupational exposure as a heating system installation worker. The family history reported malignant cancers in first-degree (larynx, brother; pleura and lung, mother), second-degree (lung, aunt and uncle) and third-degree (lung, cousin) relatives. The study reveals the potential existence of the mesothelioma risk among pastry cooks and highlights the fact that inherited factors may be involved in the development of this tumour.}, } @article {pmid9750936, year = {1998}, author = {Frank, AL and Dodson, RF and Williams, MG}, title = {Carcinogenic implications of the lack of tremolite in UICC reference chrysotile.}, journal = {American journal of industrial medicine}, volume = {34}, number = {4}, pages = {314-317}, doi = {10.1002/(sici)1097-0274(199810)34:4<314::aid-ajim3>3.0.co;2-s}, pmid = {9750936}, issn = {0271-3586}, mesh = {Asbestos, Amphibole/adverse effects/*analysis/chemistry ; Asbestos, Serpentine/adverse effects/*analysis/chemistry ; Carcinogens/adverse effects/*analysis ; Humans ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Microscopy, Electron ; Reference Values ; Sensitivity and Specificity ; }, abstract = {Using light and electron microscopy analysis, as well as electron diffraction, and energy-dispersive x-ray analysis, an aliquot of UICC chrysotile B was analyzed with special attention given to any tremolite contamination. Polarized light microscopy, with its limit of detection of approximately 1 micron when using dispersion staining, revealed chrysotile as the only fibrous asbestos component. Analytical electron microscopy at 333,000x of more than 20,000 consecutive fibers showed only the tubular morphology characteristic of chrysotile. These findings highlight that when this sample was used for exposure disease induced in animal models correlates with chrysotile-induced pathology, and does not support an explanation based on the "amphibole hypothesis." Thus, chrysotile should be considered as having the biologic ability to produce cancers, including mesotheliomas, based on the extensive use of this material as a standard reference material.}, } @article {pmid9731819, year = {1998}, author = {Ojeda, HF and Mech, K and Hicken, WJ}, title = {Localized malignant mesothelioma: a case report.}, journal = {The American surgeon}, volume = {64}, number = {9}, pages = {881-885}, pmid = {9731819}, issn = {0003-1348}, mesh = {Aged ; Anorexia/diagnosis ; Asbestos/adverse effects ; Biopsy ; Carcinoembryonic Antigen/analysis ; Fatigue/diagnosis ; Fever/diagnosis ; Humans ; Immunohistochemistry ; Keratins/analysis ; Lewis X Antigen/analysis ; Male ; Mesothelioma/*diagnosis ; Occupational Exposure ; Pleural Neoplasms/*diagnosis ; Prognosis ; Smoking/adverse effects ; Survival Rate ; Tomography, X-Ray Computed ; Vimentin/analysis ; }, abstract = {Localized malignant mesothelioma is an extremely rare form of presentation of malignant mesotheliomas. Only six cases have been reported. A 66-year-old male, former smoker, with occupational exposure to asbestos for 35 years, presented complaining of increasing fatigability, low-grade fever and anorexia for 4 weeks. The chest radiography showed a left lung mass. The computed tomography showed a 5-cm left posterior mass. The biopsy showed malignant cells. The patient underwent a surgical en bloc resection of the tumor. Pathology revealed a localized, poorly differentiated mesothelioma. Immunohistochemistry was positive for cytokeratin and vimentin while negative for carcinoembryonic antigen and Leu-M1. The final diagnosis was localized malignant mesothelioma. Aggressive resection of the tumor has shown to increase survival in previous reports, although the biological behavior of such tumors is still difficult to predict.}, } @article {pmid9730872, year = {1998}, author = {Kinnula, VL and Linnala, A and Viitala, E and Linnainmaa, K and Virtanen, I}, title = {Tenascin and fibronectin expression in human mesothelial cells and pleural mesothelioma cell-line cells.}, journal = {American journal of respiratory cell and molecular biology}, volume = {19}, number = {3}, pages = {445-452}, doi = {10.1165/ajrcmb.19.3.2884}, pmid = {9730872}, issn = {1044-1549}, mesh = {Asbestos, Amosite/pharmacology ; Fibronectins/*metabolism ; Gene Expression Regulation/drug effects ; Humans ; Hydrogen Peroxide/pharmacology ; Immunohistochemistry ; Lung Diseases/*physiopathology ; Pleural Neoplasms/*metabolism ; RNA, Messenger/metabolism ; Tenascin/*metabolism ; Transforming Growth Factor beta/pharmacology ; Tumor Cells, Cultured ; Tumor Necrosis Factor-alpha/pharmacology ; Vitamin K/pharmacology ; }, abstract = {Fibronectin (Fn) and tenascin (Tn) are two major extracellular matrix (ECM) glycoproteins that may have important roles both in fibrotic lung diseases and in lung tumors. The significance of Fn and Tn in human pleural mesothelial cells and pleural diseases is unclear. Transformed human pleural mesothelial cells (Met5A), primary cultures of mesothelial cells, and cultured mesothelioma cell lines were investigated for Fn and Tn immunoreactivity. Mesothelial cells were exposed for 48 to 96 h to transforming growth factor-beta (TGF-beta), tumor necrosis factor-alpha (TNF-alpha), amosite asbestos fibers, or oxidants (H2O2 and menadione, a compound that auto-oxidizes to produce superoxide). Immunofluorescence and Western blotting with monoclonal anti-Fn and anti-Tn antibodies, and Northern blotting with a complementary DNA (cDNA) probe for Tn showed that mesothelial cells are capable of producing Fn and Tn. The mRNA level and immunoreactivity of Tn was enhanced by TGF-beta and TNF-alpha, whereas Fn was intensified only by TGF-beta. A wide range of amosite, H2O2, or menadione concentrations had no clear effect on Fn or Tn reactivity. Fn and Tn were present at low or undetectable concentrations in five of six mesothelioma cell lines, whereas the organization of Fn immunoreactivity in these cell lines was variable. Furthermore, results obtained with the tumor tissue of these same mesothelioma patients suggested that Fn and Tn expressions do not necessarily parallel either each other or results obtained with the cultured cells.}, } @article {pmid9728617, year = {1998}, author = {Henderson, DW and Shilkin, KB and Whitaker, D}, title = {Reactive mesothelial hyperplasia vs mesothelioma, including mesothelioma in situ: a brief review.}, journal = {American journal of clinical pathology}, volume = {110}, number = {3}, pages = {397-404}, doi = {10.1093/ajcp/110.3.397}, pmid = {9728617}, issn = {0002-9173}, mesh = {Biopsy ; Diagnosis, Differential ; Epithelium/metabolism/pathology ; Humans ; Hyperplasia/*diagnosis/metabolism ; Immunoenzyme Techniques ; Mesothelioma/*diagnosis/metabolism ; Mucin-1/metabolism ; Nucleolus Organizer Region/metabolism ; Precancerous Conditions/*diagnosis/metabolism ; Silver Nitrate ; Silver Staining ; }, abstract = {In biopsy tissue, discrimination between reactive mesothelial hyperplasia and epithelial mesothelioma can pose a major problem for the surgical pathologist. Confidence in the diagnosis is often proportional to the amount of tissue available for study and depends largely on findings of invasion and the extent and cytologic atypia of the lesion, because there is no marker specific for the mesothelium and that discriminates consistently among normal, hyperplastic, and neoplastic mesothelial tissue. Therefore, mesothelioma in situ is diagnosable only when invasive epithelial mesothelioma is demonstrable in the same specimen, in a follow-up biopsy specimen, or at autopsy. Comparison of 22 cases of mesothelioma in situ that fulfill these requirements for diagnosis with 141 invasive mesotheliomas and 78 reactive mesothelioses indicates that strong linear membrane-related labeling for epithelial membrane antigen and silver-labeled nucleolar organizer region-positive material that occupies 0.6677 microm2 or more of the nucleus in an atypical in situ mesothelial lesion of the pleura are found consistently in neoplastic mesothelial cells. Although these findings may engender suspicion of mesothelioma in situ in high-risk persons, the criteria for diagnosis of pure mesothelial lesions of this type are still under study. Mesothelioma in situ should be considered proved only when unequivocal invasion is identified in a different area of the pleura or at a different time; a diagnosis of pure mesothelioma in situ should not be made in patients not exposed to asbestos.}, } @article {pmid9721831, year = {1998}, author = {Gold, B and Kathren, RL}, title = {Causes of death in a cohort of 260 plutonium workers.}, journal = {Health physics}, volume = {75}, number = {3}, pages = {236-240}, doi = {10.1097/00004032-199809000-00001}, pmid = {9721831}, issn = {0017-9078}, mesh = {Aged ; Astrocytoma/etiology/mortality ; Brain Neoplasms/etiology/mortality ; *Cause of Death ; Cohort Studies ; Female ; Glioblastoma/etiology/mortality ; Humans ; Male ; Mesothelioma/etiology/mortality ; Middle Aged ; Neoplasms, Radiation-Induced/etiology/mortality ; Occupational Diseases/etiology/mortality ; *Occupational Exposure ; Plutonium/*adverse effects ; Registries ; United States/epidemiology ; }, abstract = {The United States Transuranium and Uranium Registries (USTUR) is a unique postmortem research study of the biokinetics, dosimetry, and possible biological effects of actinide elements in persons with occupational exposure to these radioelements. Evaluation of the causes of death in the admittedly biased self-selected cohort of the first 260 deceased participants in the USTUR revealed, in general, no apparently elevated causes of death except for six cases of mesothelioma and six cases of astrocytoma glioblastoma multiforme. The mesothelioma cases had a documented occupational exposure to asbestos, and the six brain tumor deaths all occurred at a single work site and were not radiation related but rather are likely attributable to a factor specific to the work site or surrounding area. Incidental findings in this cohort did not suggest any radiation related illness or cause of death.}, } @article {pmid9692513, year = {1998}, author = {Wilsher, ML and Veale, AG}, title = {Medical thoracoscopy in the diagnosis of unexplained pleural effusion.}, journal = {Respirology (Carlton, Vic.)}, volume = {3}, number = {2}, pages = {77-80}, doi = {10.1111/j.1440-1843.1998.tb00100.x}, pmid = {9692513}, issn = {1323-7799}, mesh = {Adult ; Aged ; Aged, 80 and over ; Diagnosis, Differential ; False Negative Reactions ; Female ; Humans ; Male ; Mesothelioma/diagnosis ; Middle Aged ; Pleural Effusion/*diagnosis ; Pleural Neoplasms/diagnosis ; *Thoracoscopy/methods ; Tuberculosis, Pleural/diagnosis ; }, abstract = {Approximately 20% of pleural effusions remain without an established aetiology after evaluation. Thoracoscopy has a very high sensitivity for the diagnosis of both benign and malignant diseases and greatly increases the diagnostic yield for pleural effusion. We sought to evaluate the diagnostic yield and safety of medical thoracoscopy at this institution. The records of all patients undergoing medical thoracoscopy for the evaluation of undiagnosed pleural effusion between 1990 and 1996 were reviewed. The procedure was performed under local anaesthesia with sedation using a Stortz rigid thoracoscope. Fifty-eight patients had thoracoscopy, most having had two (range: 1-6) non-diagnostic pleural aspirations and biopsies of the pleura. Nineteen patients were found to have mesothelioma and nine metastatic malignancy. Three patients were considered likely to have tuberculous pleural disease, six had asbestos related benign pleural fibrosis and three post-cardiotomy syndrome. There was one chylous effusion of uncertain aetiology, one posttraumatic and two other benign effusions, both of which resolved without clear aetiology. On seven occasions the pleural space could not be adequately accessed, but none of these patients had prior computerized tomography (CT) or ultrasound of the pleural space. There were five false negative diagnoses of malignancy, but no false positives. The diagnostic sensitivity for pleural malignancy was 85% and specificity 100%. There were no major complications, but four patients had late tumour seeding at the thoracoscopy site. Medical thoracoscopy is a safe procedure with a high diagnostic yield. Pre-operative evaluation of the pleural collection using ultrasound or CT increases the likelihood of successful access to the pleural space and may increase diagnostic yield.}, } @article {pmid9690555, year = {1998}, author = {Beer, TW}, title = {Cancer among spouses: review of 195 couples.}, journal = {Cancer}, volume = {83}, number = {3}, pages = {591-592}, doi = {10.1002/(sici)1097-0142(19980801)83:3<591::aid-cncr32>3.0.co;2-p}, pmid = {9690555}, issn = {0008-543X}, mesh = {Asbestos/adverse effects ; Humans ; Mesothelioma/*epidemiology ; Pleural Neoplasms/*epidemiology ; *Spouses ; }, } @article {pmid9690437, year = {1998}, author = {Demiruglu, H}, title = {Hazards of white asbestos.}, journal = {Lancet (London, England)}, volume = {352}, number = {9124}, pages = {322-323}, doi = {10.1016/s0140-6736(05)60299-1}, pmid = {9690437}, issn = {0140-6736}, mesh = {Asbestos, Serpentine/*adverse effects ; Carcinogens/*adverse effects ; Environmental Exposure/*adverse effects ; Female ; Humans ; Incidence ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology ; Smoking/epidemiology ; Turkey/epidemiology ; }, } @article {pmid9689813, year = {1998}, author = {Ribotta, M and Roseo, F and Salvio, M and Castagneto, B and Carbone, M and Procopio, A and Giordano, A and Mutti, L}, title = {Recurrent chromosome 6 abnormalities in malignant mesothelioma.}, journal = {Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace}, volume = {53}, number = {2}, pages = {228-235}, pmid = {9689813}, issn = {1122-0643}, mesh = {Adult ; Aged ; Aged, 80 and over ; Chromosome Aberrations/*diagnosis ; Chromosome Disorders ; *Chromosomes, Human, Pair 6 ; Cytogenetics ; Female ; Humans ; Male ; Mesothelioma/diagnosis/*genetics ; Middle Aged ; Pleural Effusion, Malignant/genetics ; Pleural Neoplasms/diagnosis/*genetics ; Ploidies ; Recurrence ; Tumor Cells, Cultured ; }, abstract = {The long latency period between asbestos exposure and the onset of malignant mesothelioma (MM) suggests that a multistep tumorigenesis process occurs whilst the capability of asbestos fibres to interfere directly with chromosomes focuses on the critical role of the chromosomal abnormalities in this neoplasm. The aim of our study was to identify any recurrent chromosomal changes in ten primary MM cell cultures derived from pleural effusions of patients with MM from the same geographic area and environmental and/or occupational exposure to asbestos fibers. Cytogenetic analysis was performed in accordance with International System for Human Cytogenetic Nomenclature. Our results confirmed a great number of cytogenetic abnormalities in MM cells. Recurrent loss of the long arms of chromosome 6 (6q-) was the most frequent abnormality detected (four epithelial and two mixed subtypes) while, on the whole, abnormalities of chromosome 6 were found in nine out of ten cases whereas chromosome 6 was normal only in the case with fibromatous subtype. Monosomy 13 and 17 was found in five cases, monosomy 14 in four cases and 22 in three cases. Since deletion of 6q- was detected even in relatively undisturbed karyotype, we hypothesize a multistep carcinogenic process in which deletion of 6q- is an early event in the development and progression of malignant mesothelioma.}, } @article {pmid9689812, year = {1998}, author = {Valle, MT and Castagneto, B and Procopio, A and Carbone, M and Giordano, A and Mutti, L}, title = {Immunobiology and immune defense mechanisms of mesothelioma cells.}, journal = {Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace}, volume = {53}, number = {2}, pages = {219-227}, pmid = {9689812}, issn = {1122-0643}, mesh = {Asbestos/adverse effects/*immunology ; Humans ; Mesothelioma/etiology/*immunology ; Pleural Neoplasms/*immunology ; Tumor Cells, Cultured ; }, abstract = {Malignant mesothelioma (MM) is an aggressive tumor whose incidence is expected to rise in future years. Patients with this neoplasm have a poor prognosis. Immunotherapy has been shown to be effective in some neoplasms (e.g. melanoma), significantly improving their prognosis but we do not yet have sufficient data on the capability of MM cells to elicit an immune response. A "three step" event is required to determine an immune response: adhesion, recognition, and costimulation between the antigen presenting cells and the immunoeffector cells. Lack of one of these three steps leads to a defective immune response. The most important mechanism determining the defective immune response to the tumor cells is supposed to be the deficiency of the molecules involved in this "three step event", the release of immuno-depressant factors by the tumor cells and/or the tumor infiltrating cells and the lack of surface immunogen epitopes. Investigations on MM cells are not univocal, suggesting that, at least in some cases, an effective immune response to this neoplasm can occur. Blocking the release of immunodepressant factors by malignant mesothelioma cells and identification of effective, specific immunogen epitopes seem to be the most promising objective to achieve.}, } @article {pmid9689809, year = {1998}, author = {Mutti, L and Carbone, M and Giordano, GG and Giordano, A}, title = {Simian virus 40 and human cancer.}, journal = {Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace}, volume = {53}, number = {2}, pages = {198-201}, pmid = {9689809}, issn = {1122-0643}, mesh = {Animals ; Asbestosis/*virology ; Brain Neoplasms/*virology ; Cell Cycle ; Cell Transformation, Neoplastic ; Cricetinae ; Humans ; Mesothelioma/*virology ; Papillomavirus Infections/*pathology ; Simian virus 40/*isolation & purification ; Tumor Virus Infections/*pathology ; }, abstract = {Deoxyribonucleic acid (DNA) oncoviruses can induce neoplastic transformation by interfering with proliferative proteins. Simian virus 40 (SV40) has been shown to induce brain tumors, osteosarcoma, lymphoid tumors and malignant mesothelioma in hamsters and SV40-like DNA sequences corresponding to the Rb-pocket binding domain of SV40 T-antigen (Tag) have been detected in the same human tumors. Since only a small percentage of people exposed to asbestos fibers develop a malignant mesothelioma, SV40 has been suspected to co-operate with the fibers in the neoplastic transformation or even to itself induce the onset of malignant mesothelioma in patients without expositive history. The mechanism that seems to be involved in the SV40-induced carcinogenesis process is mediated by interaction of Tag, both with p53 and Rb proteins, leading to their functional inactivation that is responsible for the removal of their inhibitory cell cycle effect which determines the increase of the number of cells entering the G1-S phase. Up to now the source of SV40 human infections has not yet been completely identified even though administration from 1957-1965 of SV40 contaminated polio vaccines is highly suspected. Horizontal infection by sexual transmission has been also hypothesized. Due to the important public health implications further investigations are required in order to establish both the source and the carcinogenetic role of simian virus 40 in humans.}, } @article {pmid9689807, year = {1998}, author = {de Cupis, A and Pirani, P and Favoni, RE}, title = {Establishment and preliminary characterization of human malignant mesothelioma cell lines.}, journal = {Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace}, volume = {53}, number = {2}, pages = {188-192}, pmid = {9689807}, issn = {1122-0643}, mesh = {Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Cell Division ; Female ; Humans ; Insulin-Like Growth Factor I/pharmacology ; Male ; Mesothelioma/etiology/*pathology ; Pleural Effusion, Malignant/cytology/*pathology ; Pleural Neoplasms/etiology/*pathology ; Sensitivity and Specificity ; Tumor Cells, Cultured/drug effects ; }, abstract = {Malignant mesothelioma is an aggressive and rare tumor of the mesothelium which arises in serosal cavities and is strongly related to asbestos exposure. The incidence of this tumor is still increasing because of the widespread use of asbestos over the past years and the long latency of this malignancy. The paucity of well-characterized in vitro human models and the consequent shortage of experimental pharmacological studies on mesothelioma reduce the success of its clinical management. It is well known that established human cell lines represent a rapid and advantageous system for in vitro studies of several diseases, such as mesothelioma. Thus, the aim of our study was to establish and characterize a panel of selected human malignant mesothelioma cell lines in order to highlight the biology of this tumor and to test the effectiveness of new antiproliferative compounds. During the last year, we collected 10 pleural effusion samples from patients with diagnosed and pharmacologically untreated mesothelioma. Among these, we were able to isolate three continuously growing cell lines, identified as IST-Mes1, IST-Mes2 and IST-Mes3. Another previously established malignant mesothelioma cell line (MPP89) has also been included in this study. The cells in culture appeared morphologically heterogeneous: three of them (IST-Mes1, IST-Mes2, and MPP89) were spindle-shaped, and upon reaching confluence, they assumed the characteristic cobblestone-like pattern, whereas IST-Mes3 showed mixed sizes and shapes. Cell growth studies revealed that all cell lines reach exponential growth phase within 4-7 days after plating with a doubling time ranging from 37-87 hours. Finally, insulin-like growth factor-I did not stimulate cellular proliferation of both the IST-Mes1 and IST-Mes2 cell lines.}, } @article {pmid9689804, year = {1998}, author = {Langer, AM and Nolan, RP}, title = {Asbestos in the lungs of persons exposed in the USA.}, journal = {Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace}, volume = {53}, number = {2}, pages = {168-180}, pmid = {9689804}, issn = {1122-0643}, mesh = {Aged ; Asbestos/adverse effects/*analysis ; Asbestos, Amosite/analysis ; Asbestos, Amphibole/analysis ; Asbestos, Crocidolite/analysis ; Asbestos, Serpentine/analysis ; Asbestosis/etiology/mortality/*pathology ; Autopsy ; Biopsy ; Female ; Humans ; Lung/*ultrastructure ; Lung Neoplasms/etiology/mortality/*pathology ; Male ; Microscopy, Electron ; Middle Aged ; Occupational Exposure/adverse effects/*classification/statistics & numerical data ; Organ Culture Techniques ; United States/epidemiology ; }, abstract = {Tissues obtained at autopsy or biopsy from 81 workers and 2 household persons, were chemically digested. The asbestos fibres recovered were characterized by analytical transmission electron microscopy. Among the 83 causes of death were 33 mesotheliomas, 35 lung cancers, 12 asbestosis and 3 from other cancers. Of the three major commercial asbestos fibre types, amosite was found to be the most prevalent fibre, occurring in approximately 76% of the cases, followed by chrysotile in approximately 60% and crocidolite in approximately 24%. Amosite and chrysotile were observed as the single commercial fibre in approximately 22 and approximately 17% of the cases respectively, whereas crocidolite and tremolite were found as the single fibre type in only approximately 2.5% of the cases. Among the fifteen cases where chrysotile and tremolite occurred together, the amount of chrysotile fibre always exceeded tremolite. However, tremolite was also found in ten additional cases where chrysotile was not detected. Amosite was present in four, amosite plus crocidolite in three, and crocidolite alone in one. Amosite was present in all of the insulation workers' lungs studied and was found in the highest concentration in this exposure category. The highest chrysotile concentration was found among workers in general trades. Although most prevalent in shipyard workers lungs, crocidolite concentration is not statistically different among the exposure groups studied. Although crocidolite was found in twenty cases, amosite accompanied it in eighteen of these. Eleven of the 20 cases were from shipyard workers. Of the 8 mesothelioma cases, 7 also contained amosite. Crocidolite alone only occurred in 1 of the 33 mesothelioma cases analysed. We concluded the following: crocidolite exposure occurred among USA insulators and a large percentage of other workers as well; insulation workers are primarily exposed to amosite; mixed fibre exposures are associated with more mesotheliomas than single fibre exposures; chrysotile only exposure is associated with approximately 12% of the mesothelioma cases studied; and if tremolite exposure is associated with chrysotile exposure, the chrysotile amount exceeds that for the associated tremolite.}, } @article {pmid9688948, year = {1998}, author = {Narasimhan, SR and Yang, L and Gerwin, BI and Broaddus, VC}, title = {Resistance of pleural mesothelioma cell lines to apoptosis: relation to expression of Bcl-2 and Bax.}, journal = {The American journal of physiology}, volume = {275}, number = {1}, pages = {L165-71}, doi = {10.1152/ajplung.1998.275.1.L165}, pmid = {9688948}, issn = {0002-9513}, support = {ES-06331/ES/NIEHS NIH HHS/United States ; ES-08985/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Apoptosis/drug effects/*physiology ; Asbestos/*toxicity ; Cells, Cultured ; Epithelial Cells/cytology/drug effects/physiology ; Humans ; Hydrogen Peroxide/*pharmacology ; Mesothelioma/metabolism/*pathology ; Pleural Neoplasms/metabolism/*pathology ; Proto-Oncogene Proteins/*biosynthesis ; Proto-Oncogene Proteins c-bcl-2/*biosynthesis ; Rabbits ; Tumor Cells, Cultured ; Tumor Suppressor Protein p53/biosynthesis ; bcl-2-Associated X Protein ; }, abstract = {A failure of normal apoptosis, often due to mutant p53, may contribute to the formation of a cancer and to its resistance to therapy. Mesothelioma, an asbestos-induced tumor, is highly resistant to therapy but generally expresses wild-type p53. We asked whether mesothelioma was resistant to apoptosis and whether resistance was associated with altered expression of the antiapoptotic protein Bcl-2 or proapoptotic protein Bax. We found that three mesothelioma cell lines (1 with wild-type p53) were highly resistant to apoptosis induced by oxidant stimuli (asbestos, H2O2) or nonoxidant stimuli (calcium ionophore) compared with primary cultured mesothelial cells. By immunostaining, one of these three lines expressed Bcl-2 but only during mitosis. By immunoblotting, 3 of 14 additional mesothelioma lines (9 of 14 with wild type p53) expressed Bcl-2 but all 14 of 14 expressed the proapoptotic Bax, giving a low ratio of Bcl-2 to Bax. We conclude that mesothelioma cell lines are resistant to apoptosis and that the failure in apoptosis is not explained by Bcl-2 but by other mechanisms that counteract the proapoptotic effect of Bax.}, } @article {pmid9676695, year = {1998}, author = {Siemiatycki, J and Boffetta, P}, title = {Invited commentary: Is it possible to investigate the quantitative relation between asbestos and mesothelioma in a community-based study?.}, journal = {American journal of epidemiology}, volume = {148}, number = {2}, pages = {143-147}, doi = {10.1093/oxfordjournals.aje.a009617}, pmid = {9676695}, issn = {0002-9262}, mesh = {Asbestos/*adverse effects ; Bias ; Case-Control Studies ; Cohort Studies ; Humans ; Male ; Mesothelioma/diagnosis/*etiology ; Occupational Exposure/analysis ; Pleural Neoplasms/diagnosis/*etiology ; Risk Assessment ; }, } @article {pmid9676694, year = {1998}, author = {Iwatsubo, Y and Pairon, JC and Boutin, C and Ménard, O and Massin, N and Caillaud, D and Orlowski, E and Galateau-Salle, F and Bignon, J and Brochard, P}, title = {Pleural mesothelioma: dose-response relation at low levels of asbestos exposure in a French population-based case-control study.}, journal = {American journal of epidemiology}, volume = {148}, number = {2}, pages = {133-142}, doi = {10.1093/oxfordjournals.aje.a009616}, pmid = {9676694}, issn = {0002-9262}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Case-Control Studies ; Dose-Response Relationship, Drug ; Female ; France/epidemiology ; Humans ; Logistic Models ; Male ; Mesothelioma/epidemiology/*etiology ; Middle Aged ; Occupational Exposure/adverse effects/analysis ; Occupations ; Pleural Neoplasms/epidemiology/*etiology ; Probability ; }, abstract = {A hospital-based case-control study of the association between past occupational exposure to asbestos and pleural mesothelioma was carried out in five regions of France. Between 1987 and 1993, 405 cases and 387 controls were interviewed. The job histories of these subjects were evaluated by a group of experts for exposure to asbestos fibers according to probability, intensity, and frequency. A cumulative exposure index was calculated as the product of these three parameters and the duration of the exposed job, summed over the entire working life. Among men, the odds ratio increased with the probability of exposure and was 1.2 (95% confidence interval (CI) 0.8-1.9) for possible exposure and 3.6 (95% CI 2.4-5.3) for definite exposure. A dose-response relation was observed with the cumulative exposure index: The odds ratio increased from 1.2 (95% CI 0.8-1.8) for the lowest exposure category to 8.7 (95% CI 4.1-18.5) for the highest. Among women, the odds ratio for possible or definite exposure was 18.8 (95% CI 4.1-86.2). We found a clear dose-response relation between cumulative asbestos exposure and pleural mesothelioma in a population-based case-control study with retrospective assessment of exposure. A significant excess of mesothelioma was observed for levels of cumulative exposure that were probably far below the limits adopted in most industrial countries during the 1980s.}, } @article {pmid9659538, year = {1998}, author = {McGavin, C and Hughes, P}, title = {Finger clubbing in malignant mesothelioma and benign asbestos pleural disease.}, journal = {Respiratory medicine}, volume = {92}, number = {4}, pages = {691-692}, doi = {10.1016/s0954-6111(98)90519-4}, pmid = {9659538}, issn = {0954-6111}, mesh = {Asbestosis/*complications ; Humans ; Incidence ; Male ; Mesothelioma/*complications ; Osteoarthropathy, Secondary Hypertrophic/diagnosis/*etiology ; Pleural Neoplasms/*complications ; }, } @article {pmid9657657, year = {1998}, author = {Yilmaz, UM and Utkaner, G and Yalniz, E and Kumcuoglu, Z}, title = {Computed tomographic findings of environmental asbestos-related malignant pleural mesothelioma.}, journal = {Respirology (Carlton, Vic.)}, volume = {3}, number = {1}, pages = {33-38}, doi = {10.1046/j.1440-1843.1998.00069.x}, pmid = {9657657}, issn = {1323-7799}, mesh = {Adult ; Asbestos/*adverse effects ; Female ; Humans ; Male ; Mesothelioma/*diagnostic imaging/epidemiology/pathology ; Pleural Neoplasms/*diagnostic imaging/epidemiology/pathology ; Retrospective Studies ; Tomography, X-Ray Computed ; Turkey/epidemiology ; }, abstract = {Malignant pleural mesothelioma (MPM) is not an infrequent fatal neoplasm. It is endemically present in some regions of Turkey due to its aetiological relationship to exposure to environmental fibrous minerals. The aim of this study was to determine the thorax computed tomographic (CT) features of environmental asbestos-related MPM. In this study, we examined retrospectively the CT scans of 46 untreated patients with pathological diagnosis of environmental asbestos-related MPM among 151 patients with malignant pleural mesothelioma in the Izmir Chest Disease and Surgery Hospital. The CT scans were interpreted by consultation of four observers. Malignant pleural mesothelioma was unilateral in 45 (97.2%) of the patients. Pleural effusions were found in 42 (91%) of the patients, pleural calcifications in 12 (26%), contracted hemithorax in 14 (30%), interlobar fissure involvement in 25 (54%) and mediastinal pleural involvement in 26 (57%). A contracted hemithorax was significantly correlated with pleural rind configuration. Pleural thickenings were found in 45 (99%) of the patients. Pleural thickenings were in the form of nodularity in 10 (22%) cases, regular in 12 (27%) cases, as a focal mass in 3 (7%) cases and as a pleural rind in 20 (44%) cases. Pleural thickening was greater than 1 cm in 32 (71%) cases. The most common CT findings in our series were unilateral circumferential pleural thickening, nodular pleural thickening, pleural thickening greater than 1 cm and mediastinal pleural involvement. Generally, pleural effusion was accompanied by this. There was interlobar fissure involvement in half of the patients. There was no pathognomonic CT finding in environmental asbestos-related MPM. But CT was useful in suggesting the diagnosis of malignant pleural disease in the cases with MPM.}, } @article {pmid9651631, year = {1998}, author = {Rosenman, KD and Reilly, MJ}, title = {Asbestos-related x-ray changes in foundry workers.}, journal = {American journal of industrial medicine}, volume = {34}, number = {2}, pages = {197-201}, doi = {10.1002/(sici)1097-0274(199808)34:2<197::aid-ajim14>3.0.co;2-q}, pmid = {9651631}, issn = {0271-3586}, support = {U60/CCU502998//PHS HHS/United States ; }, mesh = {Aged ; Asbestosis/*diagnostic imaging/epidemiology ; Dust ; Humans ; Lung Neoplasms/epidemiology/etiology ; Male ; Mesothelioma/epidemiology/etiology ; *Metallurgy ; Michigan/epidemiology ; Middle Aged ; Occupational Diseases/*diagnostic imaging/epidemiology ; Population Surveillance ; Radiography ; Silicosis/epidemiology ; Smoking/adverse effects ; Time Factors ; }, abstract = {Michigan has a statewide mandatory occupational disease reporting system. As part of that system, reports are received from hospital, physicians, death certificates, the worker's compensation bureau, and company medical departments. Based on this reporting, the State of Michigan has a special emphasis program for the surveillance of silicosis, a known disease outcome among foundry workers. From 1985-1996, 115 cases reported to the State Surveillance System as silicosis, pneumoconiosis not specified, or pulmonary fibrosis were reclassified as having asbestos related x-ray changes after a B-reader interpretation of each case's chest x-ray. During this same period there were an additional 697 reports confirmed as silicosis and 6,724 cases reported to the surveillance system as asbestosis. Among the 115 reports reclassified as having asbestos-related x-ray changes without evidence of silicosis-related x-ray changes, 54 had worked in foundries. Only 7 (14.8%) of these individuals had their primary work in maintenance in the foundry; 40 (85.1%) had their primary foundry work in a production job; and for 10 individuals the occupation was not known. Asbestos has been used in foundries on pipe laggings, boiler coverings, as insulation in fan housings, in gloves, aprons and curtains, as insulation in cupolas, and in ladles and insulation in sand molds. Clinicians caring for foundry workers need to be aware that asbestos-related x-ray changes are not uncommon in this population and asbestos exposure should be considered as one of the carcinogens contributing to the known increased risk of lung cancer among foundry workers.}, } @article {pmid9646983, year = {1998}, author = {Nishimura, SL and Broaddus, VC}, title = {Asbestos-induced pleural disease.}, journal = {Clinics in chest medicine}, volume = {19}, number = {2}, pages = {311-329}, doi = {10.1016/s0272-5231(05)70079-4}, pmid = {9646983}, issn = {0272-5231}, support = {CA63148/CA/NCI NIH HHS/United States ; EHS06331/EH/NCEH CDC HHS/United States ; }, mesh = {Asbestos/adverse effects ; Asbestosis/*diagnosis/pathology/prevention & control ; Cell Transformation, Neoplastic/pathology ; Humans ; Mesothelioma/diagnosis/pathology/prevention & control ; Pleura/pathology ; Pleural Neoplasms/diagnosis/pathology/prevention & control ; Structure-Activity Relationship ; Tomography, X-Ray Computed ; }, abstract = {Asbestos-induced pleural disease has become the most common manifestation of asbestos exposure. Asbestos has an unusual affinity for the pleural space and leads to plaques, benign effusions, fibrosis, and malignant mesothelioma. The explanation for its affinity for the pleura may lie in part with new evidence showing that asbestos fibers can accumulate in certain regions of the parietal pleura at higher concentrations than in the lung. With the control of industrial exposures to asbestos, the incidence of this disease should decrease, with the incidence of mesothelioma peaking in the years 2000 to 2020. Nonetheless, the toxic features of asbestos including shape, chemical composition, and surface characteristics should be understood to avoid toxicity in fibers used to replace asbestos and to know the risks of low level exposures from asbestos currently in our environment.}, } @article {pmid9630204, year = {1998}, author = {Hiyama, J and Marukawa, M and Shiota, Y and Ono, T and Imai, S and Motohiro, K and Aoki, J and Sasaki, N and Taniyama, K and Mashiba, H}, title = {Two familial mesothelioma cases with high concentrations of soluble cytokeratin 19 fragment in pleural fluid.}, journal = {Internal medicine (Tokyo, Japan)}, volume = {37}, number = {4}, pages = {407-410}, doi = {10.2169/internalmedicine.37.407}, pmid = {9630204}, issn = {0918-2918}, mesh = {Adult ; Aged ; Antigens, Neoplasm/*metabolism ; Asbestos/adverse effects ; Biomarkers, Tumor/metabolism ; Biopsy ; Carcinogens/adverse effects ; Female ; Humans ; Keratin-19 ; Keratins ; Male ; Mesothelioma/diagnosis/*genetics/metabolism ; Occupational Exposure/adverse effects ; Pedigree ; Pleural Effusion, Malignant/diagnosis/*genetics/metabolism ; Thoracotomy ; Tomography, X-Ray Computed ; }, abstract = {We report two cases of diffuse malignant pleural mesothelioma occurring almost simultaneously in one family. Patient 1 was a 42-year-old Japanese man who had worked as an electrical engineer for 25 years. Patient 2, his mother, was 69 years old. She lived for 10 years with patient 1 after he started his work, and also worked at a shipyard herself for 6 years. The concentrations of cytokeratin subunit 19 fragment (CYFRA 21-1) in pleural fluid of the two patients were 1,500 ng/ml, and 1,200 ng/ml, respectively. Measurement of CYFRA 21-1 concentration in the pleural fluid may be a useful tool for a diagnosis of malignant mesothelioma.}, } @article {pmid9624266, year = {1998}, author = {Levin, JL and McLarty, JW and Hurst, GA and Smith, AN and Frank, AL}, title = {Tyler asbestos workers: mortality experience in a cohort exposed to amosite.}, journal = {Occupational and environmental medicine}, volume = {55}, number = {3}, pages = {155-160}, pmid = {9624266}, issn = {1351-0711}, mesh = {Adult ; Aged ; Asbestos, Amosite/*adverse effects ; Asbestosis/etiology/*mortality ; Cohort Studies ; Humans ; Male ; Mesothelioma/etiology/*mortality ; Middle Aged ; Occupational Exposure/*adverse effects ; Respiratory Tract Neoplasms/etiology/*mortality ; Retrospective Studies ; Texas/epidemiology ; Time Factors ; }, abstract = {OBJECTIVES: To examine the causes of death among 1130 former workers of a plant in Tyler, Texas dedicated to the manufacture of asbestos pipe insulation materials. This cohort is important and unusual because it used amosite as the only asbestiform mineral in the production process. High level exposure of such a specific type was documented through industrial hygiene surveys in the plant.

METHODS: Deaths were ascertained through various sources including data tapes from the Texas Department of Health and the national death index files. As many death certificates as possible were secured (304/315) and cause of death assigned. After select exclusions, 222 death certificates were used in the analysis. Causes of death were compared with age, race, and sex specific mortalities for the United States population with a commercial software package (OCMAP Version 2.0).

RESULTS: There was an excess of deaths from respiratory cancer including the bronchus, trachea, and lung (standardised mortality ratio (SMR) 277 with 95% confidence interval (95% CI) 193 to 385). Four pleural mesotheliomas and two peritoneal mesotheliomas were identified. The analysis also showed an increasing risk of respiratory malignancy with increased duration of exposure including a significant excess of total deaths from respiratory cancer with less than six months of work at the plant (SMR 268 with 95% CI 172 to 399).

CONCLUSIONS: The importance of the cohort lies with the pure amosite exposure which took place in the plant and the extended period of latency which has followed. The death certificate analysis indicates the pathogenicity of amosite, the predominant commercial amphibole used in the United States. These data confirm a link between amosite asbestos and respiratory malignancy as well as mesothelioma.}, } @article {pmid9623712, year = {1998}, author = {Greenberg, M}, title = {The priority for recognizing asbestos as a multicentre carcinogen, and problems in categorizing asbestos tumours.}, journal = {The European respiratory journal}, volume = {11}, number = {4}, pages = {996}, doi = {10.1183/09031936.98.11040996}, pmid = {9623712}, issn = {0903-1936}, mesh = {Abdominal Neoplasms/chemically induced ; Animals ; *Asbestos ; *Carcinogens ; Humans ; Mesothelioma/*classification ; *Neoplasms, Multiple Primary ; Thoracic Neoplasms/chemically induced ; }, } @article {pmid9621500, year = {1998}, author = {Merler, E and Vineis, P and Miligi, L}, title = {[Occupational cancer in Italy].}, journal = {Epidemiologia e prevenzione}, volume = {22}, number = {1}, pages = {12-25}, pmid = {9621500}, issn = {1120-9763}, mesh = {Female ; Humans ; Italy/epidemiology ; Male ; Neoplasms/*epidemiology ; Occupational Diseases/*epidemiology/etiology ; Occupational Exposure/adverse effects ; Retrospective Studies ; }, abstract = {The paper is a discussion of occupational cancer in Italy. The introductory section provides the necessary context of Italian industrialization and occupational health regulation. This is followed by a review of Italian epidemiological studies of occupational cancer risks, considered in terms of relative measures of risk and Attributable Risk to carcinogenic agents or exposure circumstances. A section attempts to establish the number of workers who have been exposed to carcinogens in Italy and the intensity of their exposures. Several cohort and case-control studies have addressed the issue of occupational risks, mostly among male workers. The results of these studies suggest that the growing incidence of and mortality by mesothelioma is explained by the widespread and intense exposure to asbestos in some Italian industrial settings. A high Attributable Risk of lung tumors among male populations in industrial areas of northern Italy is explained by occupational exposures. However, insufficient data are available for the clear definition of the extent and intensity of occupational exposure to carcinogenic substances. In Italy, we need to prioritize and maximize resources in occupational cancer epidemiology and to revitalize the role of national institutions. Recent legislation has established new regulations on the handling of carcinogenic substances in industrial settings, a new list of occupational diseases, and a national registry of mesothelioma linked to asbestos exposure. These legislative changes are expected to have positive effects.}, } @article {pmid9614395, year = {1998}, author = {Magnani, C and Leporati, M}, title = {Mortality from lung cancer and population risk attributable to asbestos in an asbestos cement manufacturing town in Italy.}, journal = {Occupational and environmental medicine}, volume = {55}, number = {2}, pages = {111-114}, pmid = {9614395}, issn = {1351-0711}, mesh = {Adolescent ; Adult ; Aged ; Asbestos, Crocidolite/*adverse effects ; Asbestos, Serpentine/*adverse effects ; Child ; Child, Preschool ; Environmental Exposure/*adverse effects ; Extraction and Processing Industry ; Female ; Humans ; Infant ; Infant, Newborn ; Italy/epidemiology ; Lung Neoplasms/epidemiology/etiology/*mortality ; Male ; Middle Aged ; Occupational Diseases/epidemiology/etiology/*mortality ; Occupational Exposure/*adverse effects ; Population Surveillance ; Retrospective Studies ; Risk Assessment ; Risk Factors ; }, abstract = {OBJECTIVE: To estimate mortality from lung cancer and the risk attributable to asbestos separately for asbestos cement workers and for the general (non-occupationally exposed) population in the town of Casale Monferrato, where the largest Italian asbestos cement factory had been in operation in 1907-86. According to cancer registry data, in the same town the incidence of malignant mesothelioma in the general population is about 10 times higher than in comparable Italian provinces.

METHOD: Decedents from lung cancer in 1989-95 were nominally identified in the list of decedents kept at the Local Health Authority of Casale Monferrato. Workers in the asbestos cement factory have been identified with a search in the nominal list of workers and the same was done for the wives of asbestos cement workers. These lists have already been used in cohort studies. Sensitivity and specificity of the linkage procedure with occupational activity in asbestos cement production have been evaluated in a previous study. Population at risk was estimated on the basis of official figures and on the results of the cohort study of asbestos cement workers.

RESULTS: 227 deaths from lung cancer were included (184 men and 43 women). Among the asbestos cement workers mortalities were 234.0 x 100,000 person-years among men and 35.5 among women. Corresponding figures in the general (non-occupationally exposed) population in Casale Monferrato were 80.6 and 18.7. The rates in the general population were not higher than in the rest of the region. Attributable risk (AR) among the asbestos cement workers (and wives) is 67.5% (95% confidence interval (95% CI) 56.8 to 78.2) for men and 51.3% (95% CI 14.9 to 87.8) among women. Population AR to occupational or paraoccupational exposure in the asbestos cement production is 18.3% (95% CI 11.1 to 25.6) among men and 10.1% (95% CI 0 to 24.6) among women.

CONCLUSION: This work did not show an increase in mortality from lung cancer for the population not exposed occupationally, but a large excess was found among men and women occupationally exposed in asbestos cement production. The total burden of lung cancer due to occupational exposure to asbestos may be underestimated, as only occupational exposure in asbestos cement production was taken into consideration. Nevertheless even a single factory can be responsible for a considerable proportion of deaths from lung cancer in a population.}, } @article {pmid9614376, year = {1998}, author = {Galateau-Salle, F and Bidet, P and Iwatsubo, Y and Gennetay, E and Renier, A and Letourneux, M and Pairon, JC and Moritz, S and Brochard, P and Jaurand, MC and Freymuth, F}, title = {SV40-like DNA sequences in pleural mesothelioma, bronchopulmonary carcinoma, and non-malignant pulmonary diseases.}, journal = {The Journal of pathology}, volume = {184}, number = {3}, pages = {252-257}, doi = {10.1002/(SICI)1096-9896(199803)184:3<252::AID-PATH15>3.0.CO;2-R}, pmid = {9614376}, issn = {0022-3417}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; DNA, Viral/*analysis ; Female ; Humans ; Immunoenzyme Techniques ; Lung Diseases/virology ; Lung Neoplasms/etiology/*virology ; Male ; Mesothelioma/etiology/*virology ; Middle Aged ; Pleural Neoplasms/etiology/*virology ; Polymerase Chain Reaction ; Simian virus 40/*isolation & purification ; }, abstract = {Pleural and pulmonary malignancies are usually associated with well-known carcinogen exposure. Recently, the presence of simian virus 40 (SV40)-like DNA sequences has been detected in brain and bone-related human cancers and in pleural mesothelioma. In order to determine whether SV40-like DNA sequences are also present in bronchopulmonary carcinoma and non-malignant lung samples, 125 frozen pleural and pulmonary samples (including 21 mesotheliomas, 63 bronchopulmonary carcinomas, 8 other tumours, and 33 non-malignant samples) and 38 additional samples distant from tumours were studied for the occurrence of SV40-like DNA sequences by polymerase chain reaction (PCR) amplification followed by hybridization with specific probes. Sequences related to SV40 large T antigen (Tag) were present in 28.6 per cent of bronchopulmonary carcinomas, 47.6 per cent of mesotheliomas, and 16.0 per cent of cases with non-neoplastic pleural and pulmonary disease. No statistically significant difference in the occurrence of these DNA sequences was found between malignant mesothelioma and bronchopulmonary carcinoma, but a significantly higher number of mesothelioma cases exhibited SV40-like DNA sequences in comparison with cases of non-malignant pleural or pulmonary disease (P < 0.04). Among cases positive for SV40-like DNA sequences, a history of asbestos exposure was found in 3 out of 12 bronchopulmonary carcinomas and 8 out of 10 mesotheliomas. Immunohistochemistry using monoclonal antibodies directed against Tag did not demonstrate nuclear staining. The DNA sequences were not related to BK virus sequences, but three samples were positive with probes hybridizing with JC virus DNA sequences. In conclusion, this study demonstrates the presence of SV40-like DNA sequences in pulmonary neoplasms and in non-malignant lung tissues. It appears that the presence of SV40-like DNA is not unique to cancer.}, } @article {pmid9611971, year = {1998}, author = {Kishimoto, T and Okahara, M and Chikamori, K and Ozaki, S and Aoe, K and Ohke, M and Fujioka, H and Kimura, K and Yonei, T}, title = {[Clinical evaluation of benign asbestos pleurisy].}, journal = {Nihon Kokyuki Gakkai zasshi = the journal of the Japanese Respiratory Society}, volume = {36}, number = {1}, pages = {18-22}, pmid = {9611971}, issn = {1343-3490}, mesh = {Aged ; Asbestosis/*complications ; Biomarkers/analysis ; C-Reactive Protein/analysis ; Humans ; Hyaluronic Acid/analysis ; Lymphocyte Count ; Male ; Middle Aged ; *Occupational Exposure ; Pleural Effusion/*etiology/metabolism ; Time Factors ; }, abstract = {Seventeen cases of benign asbestos pleurisy were evaluated clinically. All cases were male and almost all cases were more than 60 years-old. Most cases presented with chief complaints of chest pain and dyspnea, but 2 cases had no complaints. Pleural effusion appeared predominantly in the right side. Six cases had 2 or 3 episodes of pleural effusion, and 1 case had 5. Ten cases had an occupational history of asbestos exposure in shipyards and 5 other cases had a history in building construction. Almost all cases had more than 30 years of exposure to asbestos and benign asbestos pleurisy appeared after more than 30 years from the first exposure to asbestos. Among the patients, 6 cases had diffuse pleural thickening and 2 cases had malignancies. Pleural fluid was bloody in 14 of 17 cases (82%) and all pleural fluid showed an exudate. Lymphocytes represented 70% and eosinophils 15% of the cellular population of the pleural fluid. Hyaluronic acid in pleural fluid in cases of benign asbestos pleurisy averaged 29.5 micrograms/ml, which was significantly (p < 0.05) lower than in malignant pleural mesothelioma. Leukocytosis in peripheral blood and a high CRP value were uncommon in benign asbestos pleurisy.}, } @article {pmid9603793, year = {1998}, author = {Camus, M and Siemiatycki, J and Meek, B}, title = {Nonoccupational exposure to chrysotile asbestos and the risk of lung cancer.}, journal = {The New England journal of medicine}, volume = {338}, number = {22}, pages = {1565-1571}, doi = {10.1056/NEJM199805283382201}, pmid = {9603793}, issn = {0028-4793}, mesh = {Adult ; Asbestos, Serpentine/*adverse effects/analysis ; Asbestosis/mortality ; Dose-Response Relationship, Drug ; Environmental Exposure/*adverse effects/analysis ; Female ; Humans ; Lung Neoplasms/*epidemiology/etiology/mortality ; Mining ; Models, Biological ; *Mortality ; Neoplasms/mortality ; Occupational Exposure/analysis ; Pleural Neoplasms/mortality ; Quebec/epidemiology ; Risk ; }, abstract = {BACKGROUND: Heavy industrial exposure to asbestos causes lung cancer and mesothelioma, but it remains unknown whether much lower environmental exposure to asbestos also causes these cancers. Nevertheless, regulatory agencies, including the Environmental Protection Agency (EPA), have assessed the risk of lung cancer by extrapolating known risks from past industrial exposure to asbestos to today's much lower environmental asbestos levels (roughly 100,000 times lower). We also tested the EPA's model for predicting the risk of asbestos-induced lung cancer in a population of women with relatively high levels of nonoccupational exposure to asbestos.

METHODS: Mortality among women in 2 chrysotile-asbestos-mining areas of the province of Quebec was compared with mortality among women in 60 control areas, and age-standardized mortality ratios were derived. With the help of an expert panel, we estimated past exposure to asbestos among women in the mining areas and used these data with the EPA's model to predict the relative risk of lung cancer. We then compared this prediction with the observed mortality ratios.

RESULTS: On the basis of the estimated exposure in the asbestos-mining areas, a relative risk of death due to lung cancer of 2.1 was predicted by the EPA's model, amounting to about 75 excess deaths from lung cancer in this population. By contrast, we calculated a standardized mortality ratio of 1.0 and a standardized proportionate mortality ratio of 1.1 (P> 0.05), suggesting that there were between 0 and 6.5 excess deaths from lung cancer among the women with nonoccupational exposure to asbestos. Seven deaths from pleural cancer were observed (relative risk=7.63; P<0.05).

CONCLUSIONS: We found no measurable excess risk of death due to lung cancer among women in two chrysotile-asbestos-mining regions. The EPA's model overestimated the risk of asbestos-induced lung cancer by at least a factor of 10.}, } @article {pmid9600019, year = {1998}, author = {Mordasini, C and Hess, B and Zimmermann, A}, title = {[Central lung embolism in chronic interstitial pneumopathy].}, journal = {Praxis}, volume = {87}, number = {16}, pages = {555-563}, pmid = {9600019}, issn = {1661-8157}, mesh = {Aged ; Aged, 80 and over ; Asbestosis/diagnosis/pathology ; Diagnosis, Differential ; Humans ; Lung/pathology ; Male ; Mesothelioma/diagnosis/pathology ; Pleura/pathology ; Pleural Neoplasms/diagnosis/pathology ; Pulmonary Embolism/*diagnosis/pathology ; Pulmonary Fibrosis/*diagnosis/pathology ; Pulmonary Heart Disease/diagnosis/pathology ; }, abstract = {An 80 year old patient with known interstitial pneumopathy of unknown etiology was hospitalized because of acute onset and rapid deterioration of dyspnea at rest within days. A foregoing neurologic investigation including CT and EEG because of prior syncopes and cramp attacks had not revealed pathologic findings. Thorax X-ray at admission showed homogenous loss of transparency on the left side, calcified basal plaques on both sides and prominent central pulmonary vessels with jumping caliber. A punctate of the leftsided pleural effusion revealed lymphocytic exsudate, normal pH, low glucose and an elevated LDH. The patient died shortly after a collapse at a bowel visit and pulmonary embolism was suspected in accordance to results from arterial blood gas analysis, ECG and chest X-ray. Neurologic symptoms could be explained by recurrent pulmonary embolism. Pleural plaques together with the punctate suggested a malignant etiology. A mesothelioma was taken into consideration, although there were no anamnestic reports on an exposition to asbestos. Autopsy revealed almost complete central embolism of the left pulmonary artery with acute cor pulmonale thus confirming the clinical suspicion. The embolus showed components of different ages of origin. Besides bronchitic and emphysematous alteration histology of the pulmonary tissue revealed interstitial and septal fibrosis with focal tissue consolidation. In one giant cell a typical asbestos body was found (in 1 out of 10 sections). In spite of missing information on an exposition to asbestos an abnormally high exposition must be taken into consideration because of the finding of an asbestos particle in relation to the amount of tissue studied. Apart from interstitial fibrosis asbestos may also cause consolidation of pulmonary tissue. Histology of plaquelike lesions revealed mesothelioma of fibrous type. This finding supports the suspicion that a major part of the pulmonary lesions was due to exposition to asbestos.}, } @article {pmid9595051, year = {1998}, author = {Teixeira, MR and Giercksky, KE and Ikonomou, IM and Heim, S}, title = {Translocation (3;3)(p14;q29) as the primary chromosome abnormality in a peritoneal mesothelioma.}, journal = {Cancer genetics and cytogenetics}, volume = {103}, number = {1}, pages = {73-75}, doi = {10.1016/s0165-4608(97)00368-3}, pmid = {9595051}, issn = {0165-4608}, mesh = {Aged ; Chromosome Aberrations/*genetics ; Chromosome Banding ; Chromosome Disorders ; Chromosomes, Human, Pair 3/*genetics ; Female ; Humans ; Karyotyping ; Mesothelioma/*genetics ; Peritoneal Neoplasms/*genetics ; Translocation, Genetic/*genetics ; }, abstract = {Mesothelioma is a relatively rare malignant neoplasm arising from the serosal lining of the pleural, peritoneal, and pericardial cavities. Mesotheliomas are known to be associated with asbestos exposure. The karyotypes of these tumors have mostly been so complex as to preclude the identification of primary chromosome abnormalities. We present the cytogenetic analysis of two macroscopically distinct abdominal tumors, both diagnosed as peritoneal mesothelioma, occurring in a woman with a history of heavy asbestos exposure. Both tumors contained the same three karyotypically abnormal but cytogenetically related clones, with a balanced t(3;3)(p14;q29) as the primary chromosomal change. The fact that several chromosome abnormalities were common to both tumors strongly indicates that they arose through intraperitoneal spreading of a single neoplastic process; that is, they were not pathogenetically independent lesions. Our findings, taken together with previously published cytogenetic data on peritoneal mesotheliomas, indicate that a proportion of these tumors may be characterized by simple, balanced chromosomal rearrangements. At least a subset of peritoneal mesotheliomas arises through the same pathogenetic mechanisms that are involved in the pleural forms of this disease.}, } @article {pmid9593405, year = {1998}, author = {Cullen, MR}, title = {Chrysotile asbestos: enough is enough.}, journal = {Lancet (London, England)}, volume = {351}, number = {9113}, pages = {1377-1378}, doi = {10.1016/S0140-6736(05)79440-X}, pmid = {9593405}, issn = {0140-6736}, mesh = {Animals ; Asbestos, Serpentine/*adverse effects ; *Carcinogens ; Humans ; Lung Neoplasms/epidemiology/*etiology/prevention & control ; Male ; Mesothelioma/epidemiology/*etiology/prevention & control ; Occupational Exposure/*adverse effects/prevention & control ; Risk Factors ; }, } @article {pmid9533946, year = {1998}, author = {Kahlos, K and Anttila, S and Asikainen, T and Kinnula, K and Raivio, KO and Mattson, K and Linnainmaa, K and Kinnula, VL}, title = {Manganese superoxide dismutase in healthy human pleural mesothelium and in malignant pleural mesothelioma.}, journal = {American journal of respiratory cell and molecular biology}, volume = {18}, number = {4}, pages = {570-580}, doi = {10.1165/ajrcmb.18.4.2943}, pmid = {9533946}, issn = {1044-1549}, mesh = {Adult ; Aged ; Antibiotics, Antineoplastic/administration & dosage/toxicity ; Antioxidants/metabolism ; Biopsy ; Cell Line, Transformed ; Epirubicin/administration & dosage/toxicity ; Epithelial Cells/drug effects/*enzymology ; Free Radical Scavengers/metabolism ; Hemostatics/administration & dosage/toxicity ; Humans ; Hydrogen Peroxide/metabolism ; Male ; Mesothelioma/*enzymology ; Middle Aged ; Pleura/*cytology/enzymology/pathology ; Pleural Neoplasms/*enzymology/pathology ; Superoxide Dismutase/drug effects/*metabolism ; Tumor Cells, Cultured ; Vitamin K/administration & dosage/toxicity ; }, abstract = {We hypothesized that manganese superoxide dismutase (MnSOD), known to be induced in rat mesothelial cells by asbestos fibers, cytokines, and hyperoxia, may also be induced in asbestos-related pleural diseases such as mesothelioma. MnSOD was assessed in healthy human pleural mesothelium (n = 6), in biopsy samples of human pleural mesothelioma (n = 7), in transformed nonmalignant human mesothelial cells (Met5A), and in two human mesothelioma cell lines (M14K and M38K) established from the tumor tissue of mesothelioma patients. There was no MnSOD immunoreactivity in five of the six samples of healthy pleural mesothelium, whereas MnSOD immunoreactivity was high in the tumor cells in all the mesothelioma samples. Northern blotting, immunohistochemistry, Western blotting, and specific activity measurements showed lower MnSOD in the nonmalignant Met5A mesothelial cells than in the M14K and M38K mesothelioma cells. In additional experiments the mesothelial and mesothelioma cells were exposed to menadione, which generates superoxide intracellularly, and to epirubicin, a cytotoxic drug commonly used to treat mesothelioma. The M38K mesothelioma cells were most resistant to menadione and epirubicin when assessed by LDH release or by adenine nucleotide (ATP, ADP, and AMP) depletion. These same cells showed not only the highest MnSOD levels, but also the highest mRNA levels and activities of catalase, whereas glutathione peroxidase and glutathione reductase levels did not differ significantly. We conclude that MnSOD expression is low in healthy human pleural mesothelium and high in human malignant mesothelioma. The most resistant mesothelioma cells contained coordinated induction of MnSOD and catalase.}, } @article {pmid9519878, year = {1998}, author = {Levresse, V and Moritz, S and Renier, A and Kheuang, L and Galateau-Salle, F and Mège, JP and Piedbois, P and Salmons, B and Guenzburg, W and Jaurand, MC}, title = {Effect of simian virus large T antigen expression on cell cycle control and apoptosis in rat pleural mesothelial cells exposed to DNA damaging agents.}, journal = {Oncogene}, volume = {16}, number = {8}, pages = {1041-1053}, doi = {10.1038/sj.onc.1201627}, pmid = {9519878}, issn = {0950-9232}, mesh = {Animals ; Antigens, Polyomavirus Transforming/biosynthesis/*physiology ; Apoptosis/drug effects/*physiology/radiation effects ; Asbestos/*toxicity ; Carcinogens/*toxicity ; Cell Cycle/drug effects/*physiology/radiation effects ; Cells, Cultured ; Chromosome Aberrations ; DNA/drug effects/metabolism/radiation effects ; *DNA Damage ; Epithelial Cells/cytology/drug effects/metabolism ; Gamma Rays/*adverse effects ; Pleura/*cytology/drug effects/*metabolism ; Proto-Oncogene Proteins p21(ras)/biosynthesis/physiology ; Rats ; Tumor Suppressor Protein p53/biosynthesis/physiology ; }, abstract = {Cell cycle progression and apoptosis are controlled by regulatory proteins, including p53, of which functional alterations are linked to carcinogenesis. Recently, malignant mesothelioma (MM), a primary tumour related to asbestos exposure, alternatively to post therapeutic radiations, has proven to be an important problem in oncogenesis. The p53 protein does not seem mutated or deleted in MM but a possible inactivation by binding to other proteins [mdm2; SV40 large T antigen (Tag)] has been suggested. The present work investigated cell cycle regulation in normal rat pleural mesothelial cells (RPMC) and in RPMC expressing Tag (RPMC-TSV40), under exposure to asbestos and radiations. In RPMC, these agents induced activation of cell cycle checkpoints located at G1/S and G2/M and/or mitosis but a lack of control at G1/S was found in RPMC-TSV40. A loss of G2/M control may account for the formation of micronuclei observed after exposure of RPMC-TSV40 to radiations. In RPMC-TSV40 the enhancement of abnormal mitoses and apoptosis after asbestos exposure, in comparison with RPMC, suggests a loss of mitotic control and a p53-independent mechanism of apoptosis. Thus Tag expression in mesothelial cells might have both adverse and beneficial effects by impairing the control of DNA integrity and enhancing apoptosis respectively.}, } @article {pmid9515850, year = {1998}, author = {Herndon, JE and Green, MR and Chahinian, AP and Corson, JM and Suzuki, Y and Vogelzang, NJ}, title = {Factors predictive of survival among 337 patients with mesothelioma treated between 1984 and 1994 by the Cancer and Leukemia Group B.}, journal = {Chest}, volume = {113}, number = {3}, pages = {723-731}, doi = {10.1378/chest.113.3.723}, pmid = {9515850}, issn = {0012-3692}, support = {CA04457/CA/NCI NIH HHS/United States ; CA31946/CA/NCI NIH HHS/United States ; CA33601/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Female ; Humans ; Male ; Mesothelioma/drug therapy/*mortality ; Middle Aged ; Pleural Neoplasms/drug therapy/mortality ; Regression Analysis ; Risk Factors ; Survival Analysis ; Survival Rate ; }, abstract = {PURPOSE: To examine the individual and joint effect of various pretreatment clinical characteristics on the survival of patients with mesothelioma treated by the Cancer and Leukemia Group B (CALGB).

PATIENTS AND METHODS: Between June 1984 and September 1994, 337 patients with malignant mesothelioma and no prior chemotherapy were accrued to seven phase II studies conducted by the CALGB which screened the efficacy of 10 treatment regimens or dose levels. The eligibility criteria for all studies were virtually identical. Patient characteristics include the following: age older than 60 years (63%); male (83%); performance status (PS) of 0 or 1 (81%); chest pain (60%); definite asbestos exposure (62%); >5% weight loss (41%); and pleural involvement (94%). Median survival time (MST) for the 10 treatment regimens ranged from 3.9 to 9.8 months (overall=7.2; 95% confidence interval [CI], 6.5 to 8.3), with 1-year survival between 14% and 50% (overall=27%; 95% CI, 23 to 33%).

RESULTS: Cox survival models and exponential regression trees were used to examine the prognostic importance of pretreatment patient characteristics. Univariate analyses show that patients with poor Eastern Cooperative Oncology Group PS, chest pain, dyspnea, platelet count (PLT) >400,000/microL, weight loss, serum lactate dehydrogenase (LDH) level >500 IU/L, pleural involvement, low hemoglobin (HGB) level, high WBC count, and increasing age over 75 years have a worse prognosis. With decreasing risk ratio, multivariate Cox analyses showed that pleural involvement, LDH >500 IU/L, poor PS, chest pain, PLT >400,000/microL, nonepithelial histology, and increasing age older than 75 years jointly predict poor survival. PS was the most important prognostic split in the regression tree. Terminal nodes were amalgamated to form six distinct prognostic subgroups with MST (2-year survival) of 13.9 (38%) in 36 patients, 9.5 (21%) in 36 patients, 9.2 (10%) in 146 patients, 6.5 (3%) in 33 patients, 4.4 (0%) in 73 patients, and 1.4 (0%) in 13 patients (p<0.0001).

CONCLUSIONS: The subgroup with the best survival (MST=13.9 months) included patients with PS=0 and age younger than 49 years, and patients with PS=0, age of 49 years or older, and HGB > or =14.6. The worst survival (MST= 1.4 months) occurred for patients with PS= 1/2 and WBC > or =15.6/microL.}, } @article {pmid9515798, year = {1998}, author = {Park, SH and Aust, AE}, title = {Participation of iron and nitric oxide in the mutagenicity of asbestos in hgprt-, gpt+ Chinese hamster V79 cells.}, journal = {Cancer research}, volume = {58}, number = {6}, pages = {1144-1148}, pmid = {9515798}, issn = {0008-5472}, support = {ES05814/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Asbestos/*toxicity ; Asbestos, Crocidolite/*toxicity ; Bacterial Proteins/physiology ; Cell Line ; Cricetinae ; DNA Damage ; Escherichia coli Proteins ; Hypoxanthine Phosphoribosyltransferase/*deficiency ; Iron/*physiology ; Mutagens/*toxicity ; Nitric Oxide/*physiology ; Oxidation-Reduction ; Pentosyltransferases ; *Proteins ; Reactive Oxygen Species ; }, abstract = {Crocidolite asbestos is known to cause cellular damage, leading to asbestosis, bronchogenic carcinoma, and mesothelioma in humans. The mechanism responsible for the carcinogenicity of asbestos is not known. Iron associated with asbestos is thought to play a role by catalyzing the formation of reactive oxygen species, which may cause DNA damage, leading to mutations and cancer. Here, we examined whether asbestos can induce mutations in Chinese hamster hgprt+ V79 cells or transgenic hgprt-, gpt+ V79 cells (G12). Treatment with 6 microg/cm2 crocidolite for 24 h caused a 2-fold increase in the mutation frequency at the gpt locus of G12 cells, but no increase at the hgprt locus of V79 cells. The mutation frequency at the gpt locus of G12 cells increased with increasing treatment dose of crocidolite. The mutations induced by crocidolite appeared to be due to the generation of reactive oxygen species catalyzed by iron associated with the fibers, because treatment of G12 cells in iron-free medium with fibers from which redox active iron had been removed with desferrioxamine B prevented all of the gpt- mutations above untreated control levels. In addition, treatment of cells with a soluble form of iron, 1.5 mM ferric ammonium citrate, resulted in an increase in mutation frequency at the gpt locus of approximately 1.5 fold above that of untreated G12 cells with no increase in mutations at the hgprt locus of V79 cells with ferric ammonium citrate. We also investigated the effect of nitric oxide on the mutagenicity of crocidolite in G12 cells. When G12 cells were treated with 3 microg/cm2 of crocidolite in the presence of nitric oxide-generating compound, 200 microM diethyltriamine/NO, the mutation frequency increased to a level that was more than additive for crocidolite or diethyltriamine/NO treatment alone. These results strongly suggest that the presence of iron and nitric oxide may either lead to the generation of another reactive, mutagenic species, such as peroxynitrite, or that nitric oxide inhibits a DNA repair enzyme(s), leading to an increase in mutations.}, } @article {pmid9493446, year = {1997}, author = {Takabe, K and Tsukada, Y and Shimizu, T and Takagiwa, J and Hirayama, M and Nakayama, M and Miura, H and Akabane, H and Takayama, S and Aida, S}, title = {[The clinical utility of asbestos body counts in bronchoalveolar lavage fluid].}, journal = {Nihon Kyobu Shikkan Gakkai zasshi}, volume = {35}, number = {11}, pages = {1196-1204}, pmid = {9493446}, issn = {0301-1542}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/adverse effects/*analysis ; Asbestosis/etiology/*metabolism ; Bronchoalveolar Lavage Fluid/*chemistry ; Female ; Humans ; Lung Neoplasms/chemistry/etiology ; Male ; Mesothelioma/chemistry/etiology ; Middle Aged ; Mineral Fibers/analysis ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/chemistry/etiology ; }, abstract = {To assess the clinical utility of measuring the number of asbestos bodies (AB) present in bronchoalveolar lavage fluid (BALF), we counted the number of AB in BALF from 119 subjects using light microscopy. The results were analyzed according to occupational histories, radiological findings of asbestos-induced lung and pleural changes, and asbestos-related diseases. The 94 subjects in group 1 had a history of dust exposure, whereas group 2 subjects (n = 25) had no dust exposure. Group 1 was subdivided into subjects with obvious exposure to asbestos (group 1A, n = 61), and subjects with no known exposure to asbestos (group 1B, n = 33). The distribution of AB counts per ml of BALF (means +/- SEM) differed significantly between groups 1 and 2 (38.8 +/- 17.4 vs 0.06 +/- 0.04, p < 0.0001). The AB counts were significantly different between groups 1A and 1B (57.9 +/- 26.6 vs 3.4 +/- 1.2, p = 0.01). Subject, exposed to dust who had radiological evidence of pleural thickening had significantly higher AB counts than subjects in whom pleural thickening was absent (66.0 +/- 31.1 vs 5.1 +/- 4.2, p = 0.03). In group 1, the BALF was positive for AB in 7 of 14 patients with pulmonary fibrosis, 4 of 5 patients with lung cancer, all 6 patients with malignant mesothelioma, and all 4 patients with benign asbestos pleural effusion. We conclude that AB counts in BALF are useful for evaluating both the history of asbestos exposure in a population exposed to dust, as well as patients having asbestos-related diseases.}, } @article {pmid9489230, year = {1997}, author = {Bonazzina, R and Azara, M and Gianera, A and Cannatelli, P and Zocchetti, C}, title = {[Ordinary epidemiology: pleural mesothelioma and asbestos].}, journal = {Epidemiologia e prevenzione}, volume = {21}, number = {4}, pages = {279-282}, pmid = {9489230}, issn = {1120-9763}, mesh = {Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Female ; Humans ; Italy ; Male ; Mesothelioma/*etiology/mortality ; Middle Aged ; Pleural Neoplasms/*etiology/mortality ; Survival Rate ; }, abstract = {This paper describes a practical experience which took place in a Health District of the Lombardy Region (Northern Italy). This experience was motivated by the publication, on a newspaper, of the results of an epidemiological study which reported the nationwide geographical distribution of the mortality data for pleural mesothelioma during the period 1980-1987. The presence of excesses of pleural mesothelioma cases in two municipalities of Health District captured the attention of some field operators which decided to start working on the topic. Using all information available in the District all cases of pleural mesothelioma occurring during the period 1978-1993 in the two municipalities were identified; possible sources of both occupational and environmental asbestos exposure in the area were identified; and the next-of-kin of the cases was interviewed so as to gain information on the history of possible exposure to asbestos of the cases. For thirteen (out of seventeen) deaths the next-of-kin accepted to be interviewed and for them results are reported: the information presented describes gender, smoking habits, and an evaluation of the potential for exposure to asbestos both of occupational and environmental origin. We discuss the value importance of the experience, with particular emphasis on: a) the routine activities of the Services participating in the study; b) the resources employed; c) the use of epidemiological methods and tools; d) the primary prevention activities originated in the area; e) the personal motivations hat such experiences are capable to convey.}, } @article {pmid9473858, year = {1998}, author = {Kitamura, F and Araki, S and Tanigawa, T and Miura, H and Akabane, H and Iwasaki, R}, title = {Assessment of mutations of Ha- and Ki-ras oncogenes and the p53 suppressor gene in seven malignant mesothelioma patients exposed to asbestos--PCR-SSCP and sequencing analyses of paraffin-embedded primary tumors.}, journal = {Industrial health}, volume = {36}, number = {1}, pages = {52-56}, doi = {10.2486/indhealth.36.52}, pmid = {9473858}, issn = {0019-8366}, mesh = {Aged ; Asbestos/*adverse effects ; Codon/genetics ; DNA Mutational Analysis ; DNA Primers ; Female ; Genes, Tumor Suppressor/genetics ; Genes, p53/*genetics ; Genes, ras/*genetics ; Humans ; Lung Neoplasms/*genetics ; Male ; Mesothelioma/*genetics ; Middle Aged ; Occupational Diseases/*genetics ; Occupational Exposure/*adverse effects ; Oncogenes/genetics ; *Point Mutation ; Polymerase Chain Reaction/methods ; Sequence Analysis, DNA ; }, abstract = {To examine whether malignant mesothelioma due to asbestos has genetic alterations in the Ha- and Ki-ras oncogenes or in the p53 suppressor gene, we analyzed the point mutations of these genes in paraffin-embedded autopsy samples of the primary tumors of malignant mesothelioma in seven asbestos patients who died from malignant mesothelioma. The genetic analysis was conducted by the polymerase chain reaction-single strand comformation polymorphysms (PCR-SSCP) method in all patients, and through the sequencing of deoxyribonucleic acid (DNA) bases in one patient. No genetic alterations were found in exons 1 or 2 of Ha- and Ki-ras oncogenes, or in exons 5 to 9 of the p53 gene, in any of the patients. Further studies on a larger number of patients are required to reach a definite conclusion concerning the genetic effects of asbestos on malignant mesothelioma.}, } @article {pmid9466557, year = {1998}, author = {Pache, JC and Janssen, YM and Walsh, ES and Quinlan, TR and Zanella, CL and Low, RB and Taatjes, DJ and Mossman, BT}, title = {Increased epidermal growth factor-receptor protein in a human mesothelial cell line in response to long asbestos fibers.}, journal = {The American journal of pathology}, volume = {152}, number = {2}, pages = {333-340}, pmid = {9466557}, issn = {0002-9440}, support = {R01ES/HL09213/ES/NIEHS NIH HHS/United States ; R01ESO6499/ES/NIEHS NIH HHS/United States ; R01ESO7038/ES/NIEHS NIH HHS/United States ; }, mesh = {Asbestos/*pharmacology ; Carcinogens/*pharmacology ; Carcinoma/metabolism/pathology ; Cell Line, Transformed ; Epithelial Cells/*drug effects/*metabolism ; ErbB Receptors/*metabolism ; Fluorescent Antibody Technique ; Humans ; Lung Neoplasms/metabolism/pathology ; Phosphotyrosine/metabolism ; Tissue Distribution ; Tumor Cells, Cultured/drug effects ; }, abstract = {Epidermal growth factor (EGF) is a potent mitogen for human mesothelial cells, and autophosphorylation of the EGF receptor (EGF-R) occurs in these cell types after exposure to asbestos, a carcinogen associated with the development of mesothelioma. Here, the intensity and distribution of EGF-R protein was documented by immunocytochemistry in a human mesothelial cell line (MET5A) exposed to various concentrations of crocidolite asbestos and man-made vitreous fibers (MMVF-10). Whereas cells in contact with or phagocytizing shorter asbestos fibers (<60 microm length) or MMVF-10 at a range of concentrations showed no increase in EGF-R protein as determined by immunofluorescence, elongated cells phagocytizing and surrounding longer fibers (> or =60 microm) showed intense staining for EGF-R. In contrast, human A549 lung carcinoma cells showed neither elongation nor increased accumulation of EGF-R protein in response to long fibers. Patterns of aggregation and increases in EGF-R protein in mesothelial cells phagocytizing long asbestos fibers were distinct from diffuse staining of phosphotyrosine residues observed in asbestos-exposed cultures. These studies indicate that aggregation of EGF-R by long fibers may initiate cell signaling cascades important in asbestos-induced mitogenesis and carcinogenesis.}, } @article {pmid9455794, year = {1998}, author = {de Klerk, NH and Musk, AW and Ambrosini, GL and Eccles, JL and Hansen, J and Olsen, N and Watts, VL and Lund, HG and Pang, SC and Beilby, J and Hobbs, MS}, title = {Vitamin A and cancer prevention II: comparison of the effects of retinol and beta-carotene.}, journal = {International journal of cancer}, volume = {75}, number = {3}, pages = {362-367}, doi = {10.1002/(sici)1097-0215(19980130)75:3<362::aid-ijc6>3.0.co;2-0}, pmid = {9455794}, issn = {0020-7136}, mesh = {Adult ; Aged ; Aged, 80 and over ; Anticarcinogenic Agents/*therapeutic use ; Asbestos, Crocidolite/*adverse effects ; Female ; Humans ; Incidence ; Lung Neoplasms/etiology/mortality/*prevention & control ; Male ; Mesothelioma/etiology/mortality/*prevention & control ; Middle Aged ; Myocardial Ischemia/etiology/prevention & control ; *Occupational Exposure ; Patient Compliance ; Risk Factors ; Smoking/adverse effects ; Vitamin A/adverse effects/*therapeutic use ; beta Carotene/adverse effects/*therapeutic use ; }, abstract = {Former blue asbestos workers known to be at high risk of asbestos-related diseases, particularly malignant mesothelioma and lung cancer, were enrolled in a chemo-prevention program using vitamin A. Our aims were to compare rates of disease and death in subjects randomly assigned to beta-carotene or retinol. Subjects were assigned randomly to take 30 mg/day beta-carotene (512 subjects) or 25,000 IU/day retinol (512 subjects) and followed up through death and cancer registries from the start of the study in June 1990 till May 1995. Comparison between groups was by Cox regression in both intention-to-treat analyses and efficacy analyses based on treatment actually taken. Median follow-up time was 232 weeks. Four cases of lung cancer and 3 cases of mesothelioma were observed in subjects randomised to retinol and 6 cases of lung cancer and 12 cases of mesothelioma in subjects randomised to beta-carotene. The relative rate of mesothelioma (the most common single cause of death in our study) for those on retinol compared with those on beta-carotene was 0.24 (95% CI 0.07-0.86). In the retinol group, there was also a significantly lower rate for death from all causes but a higher rate of ischaemic heart disease mortality. Similar results were found with efficacy analyses. Our results confirm other findings of a lack of any benefit from administration of large doses of synthetic beta-carotene. The finding of significantly lower rates of mesothelioma among subjects assigned to retinol requires further investigation.}, } @article {pmid9455793, year = {1998}, author = {Musk, AW and de Klerk, NH and Ambrosini, GL and Eccles, JL and Hansen, J and Olsen, NJ and Watts, VL and Lund, HG and Pang, SC and Beilby, J and Hobbs, MS}, title = {Vitamin A and cancer prevention I: observations in workers previously exposed to asbestos at Wittenoom, Western Australia.}, journal = {International journal of cancer}, volume = {75}, number = {3}, pages = {355-361}, doi = {10.1002/(sici)1097-0215(19980130)75:3<355::aid-ijc5>3.0.co;2-1}, pmid = {9455793}, issn = {0020-7136}, mesh = {Adult ; Aged ; Aged, 80 and over ; Anticarcinogenic Agents/*therapeutic use ; Asbestos, Crocidolite/*adverse effects ; Female ; Humans ; Lung Neoplasms/etiology/mortality/*prevention & control ; Male ; Mesothelioma/etiology/mortality/*prevention & control ; Middle Aged ; Myocardial Ischemia/etiology/mortality ; *Occupational Exposure ; Vitamin A/*therapeutic use ; }, abstract = {Our aim was to describe a vitamin A-based cancer prevention program for former asbestos workers and to check for possible harmful effects by comparing rates of disease and death in study subjects with subjects who chose not to join. All subjects had been occupationally exposed to crocidolite at Wittenoom Gorge between 1943 and 1966; 1,677 subjects indicated interest in the program and 1,203 joined between June 1990 and May 1995. Comparison subjects consisted of 996 former workers known to be alive in Western Australia in 1990 who did not join the program. Program subjects were provided with annual supplies of vitamin A (either synthetic beta-carotene or retinol), help in quitting smoking and dietary advice. The comparison group received only mail contact. Both groups were followed up to December 1994 for vital status and cancer information, and rates of cancer and death from various causes were compared. Mortality in both groups was higher than expected (standardised mortality ratio 1.23 in program subjects and 1.67 in comparison subjects). After adjustment for age, smoking and asbestos exposure, the relative rates in participants compared with non-participants was below I for all examined cancers and causes of death. For mesothelioma and lung cancer, group differences increased with time from entry, whereas other differences dissipated with time. No significant side effects were reported. In conclusion, program participants had significantly lower mortality than non-participants, but the rates of the 2 groups converged with time.}, } @article {pmid9453817, year = {1997}, author = {Cabriada, V and Antoñana, JM and Sobradillo, V and Pascal, I and Gáldiz, JB and Peña, JM}, title = {[Usefulness of computerized tomography in the study of pleural effusion with no presumed diagnosis].}, journal = {Archivos de bronconeumologia}, volume = {33}, number = {10}, pages = {503-508}, doi = {10.1016/s0300-2896(15)30532-9}, pmid = {9453817}, issn = {0300-2896}, mesh = {Aged ; Carcinoma, Renal Cell/complications ; Female ; Humans ; Kidney Neoplasms/complications ; Lymphoma, Non-Hodgkin/complications ; Male ; Mesothelioma/complications ; Ovarian Neoplasms/complications ; Pleural Effusion/diagnostic imaging/*etiology ; Pleural Neoplasms/complications ; Prospective Studies ; *Tomography, X-Ray Computed ; }, abstract = {To establish the diagnostic yield of computerized tomography (CT) in pleural effusions with no presumed diagnosis arising from standard clinical examination. A prospective protocol study enrolling all cases of effusion admitted to our hospital between January 1994 through July 1995 without a presumed diagnosis after initial testing that included thoracocentesis. Twenty-two patients were enrolled. All were given a CT scan as well as other complementary examinations considered appropriate and were referred to our outpatient clinic for follow-up. The CT images were read by an expert radiologist and their contribution was classified as "diagnostic", "suggestive" or "nil". A definitive etiologic diagnosis was achieved in 14 cases (8 neoplasms, 4 benign due to asbestos, 1 tuberculosis and 1 pulmonary embolism). The CT contribution was nil in 13 cases (59%), "diagnostic" in 6 (2 mesotheliomas, 1 hypernephroma, 1 lymphoma, 1 adenocarcinoma of the colon and another of the ovary) and "suggestive" in 3 (2 benign due to asbestos and 1 lymphoma). Positive information was obtained in 9 cases (41%). CT gives good yield in the investigation of pleural effusions with no presumed diagnosis and should be made available to this group of patients before other more invasive procedures are resorted to. It is especially useful for detecting neoplastic disease of the upper abdomen, mesothelioma and sings of unsuspected exposure to asbestos.}, } @article {pmid9445280, year = {1998}, author = {Hansen, J and de Klerk, NH and Musk, AW and Hobbs, MS}, title = {Environmental exposure to crocidolite and mesothelioma: exposure-response relationships.}, journal = {American journal of respiratory and critical care medicine}, volume = {157}, number = {1}, pages = {69-75}, doi = {10.1164/ajrccm.157.1.96-11086}, pmid = {9445280}, issn = {1073-449X}, mesh = {Adult ; Aged ; *Asbestos, Crocidolite ; *Carcinogens ; Cause of Death ; Environmental Exposure/*adverse effects/*analysis ; Female ; Follow-Up Studies ; Humans ; Incidence ; Male ; Mesothelioma/*chemically induced/*epidemiology ; Middle Aged ; Population Surveillance ; Proportional Hazards Models ; Registries ; Residence Characteristics ; Risk Factors ; Surveys and Questionnaires ; Time Factors ; Western Australia/epidemiology ; }, abstract = {This study aimed to estimate exposure-response relationships for mesothelioma and environmental exposure to crocidolite. All 4,659 former residents of Wittenoom, Western Australia (WA) who lived there between 1943 and 1993 for at least 1 mo and were not directly employed in the crocidolite industry, were followed-up through the WA death, cancer and mesothelioma registries, electoral rolls, and telephone books. In 1992, all subjects who should be traced were sent a questionnaire. Exposure levels were estimated from results of periodic environmental surveys and duration of residence. Incidence rates were standardized to the World Population and Cox Regression was used to estimate the effects of exposure on incidence. To the end of 1993, 27 cases of mesothelioma were diagnosed. Mesothelioma cases stayed longer at Wittenoom, had a higher average intensity of exposure, and a higher cumulative exposure to crocidolite than control subjects. The standardized incidence of mesothelioma was 260 per million person-years, and was similar for males and females. The rate increased significantly with time from first exposure, duration of exposure and cumulative exposure. At these levels of crocidolite exposure, there is a significantly increased risk of mesothelioma, which is dose-dependent.}, } @article {pmid9443389, year = {1998}, author = {Fung, H and Kow, YW and Van Houten, B and Taatjes, DJ and Hatahet, Z and Janssen, YM and Vacek, P and Faux, SP and Mossman, BT}, title = {Asbestos increases mammalian AP-endonuclease gene expression, protein levels, and enzyme activity in mesothelial cells.}, journal = {Cancer research}, volume = {58}, number = {2}, pages = {189-194}, pmid = {9443389}, issn = {0008-5472}, support = {ES06499/ES/NIEHS NIH HHS/United States ; ES07038/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Asbestos, Crocidolite/*pharmacology ; Blotting, Northern ; Carbon-Oxygen Lyases/genetics/*metabolism ; Carcinogens/*pharmacology ; Cells, Cultured ; DNA Primers/chemistry ; DNA Repair ; DNA-(Apurinic or Apyrimidinic Site) Lyase ; Deoxyribonuclease IV (Phage T4-Induced) ; Dose-Response Relationship, Drug ; Epithelial Cells/drug effects/*enzymology ; Fluorescent Antibody Technique, Indirect ; *Gene Expression Regulation, Enzymologic ; Microscopy, Confocal ; Mitochondria/enzymology ; Nuclear Proteins/*metabolism ; Pleura/cytology/drug effects/*enzymology ; RNA, Messenger/metabolism ; Rats ; Rats, Inbred F344 ; }, abstract = {Only two DNA repair enzymes, DNA polymerase beta and O6-methylguanine-DNA methyltransferase, have been shown to be inducible in mammalian cells by genotoxic agents. We show here that crocidolite asbestos induces the DNA repair enzyme, apurinic/apyrimidinic (AP)-endonuclease, in isolated mesothelial cells, the progenitor cells of malignant mesothelioma. Asbestos at nontoxic concentrations of 1.25 and 2.5 microg/cm2 significantly increased AP-endonuclease mRNA and protein levels as well as enzyme activity (P < 0.05) in a dose-dependent manner in rat pleural mesothelial cells. These increases were persistent from 24 to 72 h after initial exposure to fibers. Changes were not observed with glass beads, a noncarcinogenic particle. Confocal scanning laser microscopy showed that AP-endonuclease was primarily localized in the nucleus but also in mitochondria. Our data are the first to demonstrate the inducibility of AP-endonuclease by a human class I carcinogen associated with oxidant stress in normal cells of the lung.}, } @article {pmid9437800, year = {1997}, author = {Goodglick, LA and Vaslet, CA and Messier, NJ and Kane, AB}, title = {Growth factor responses and protooncogene expression of murine mesothelial cell lines derived from asbestos-induced mesotheliomas.}, journal = {Toxicologic pathology}, volume = {25}, number = {6}, pages = {565-573}, doi = {10.1177/019262339702500605}, pmid = {9437800}, issn = {0192-6233}, support = {R01 ES03189/ES/NIEHS NIH HHS/United States ; T32 GM 07601/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Asbestos, Crocidolite/*toxicity ; ErbB Receptors/biosynthesis ; Gene Expression/drug effects ; Genes, fos/*drug effects ; Genes, jun/*drug effects ; Growth Substances/*pharmacology ; Male ; Mesothelioma/*etiology/*metabolism/pathology ; Mice ; Mice, Inbred C57BL ; Proto-Oncogene Proteins c-fos/biosynthesis ; Proto-Oncogene Proteins c-jun/biosynthesis ; Tumor Cells, Cultured ; }, abstract = {Repeated intraperitoneal injections of crocidolite asbestos fibers induced diffuse malignant mesotheliomas in mice. A series of mesothelial cell lines was isolated from mice at different stages in the development of these tumors. The cell lines isolated from mice with mesotheliomas recapitulated their growth pattern in vivo and were tumorigenic when reinjected into syngeneic mice. Similar to human mesothelial cells, growth of the murine cell lines was stimulated by epidermal growth factor. Reactive mesothelial cells and mesotheliomas expressed the receptor for this growth factor. Crocidolite asbestos fibers have been reported to induce sustained expression of the c-fos and c-jun protooncogenes in rat pleural mesothelial cells in vitro (Heintz et al, Proc. Natl. Acad. Sci. USA 90: 3299-303, 1993). Human malignant mesotheliomas have been shown to express c-fos in situ (Ramael et al, Histol. Histopathol. 10: 639-643, 1995). Two of the cell lines derived from highly invasive murine mesotheliomas overexpressed c-fos and c-jun. This murine model recapitulates the histopathology, growth factor responses, and protooncogene expression of human malignant mesotheliomas.}, } @article {pmid9426114, year = {1997}, author = {Greenberg, M}, title = {History of mesothelioma.}, journal = {The European respiratory journal}, volume = {10}, number = {11}, pages = {2690-2691}, doi = {10.1183/09031936.97.10112690}, pmid = {9426114}, issn = {0903-1936}, mesh = {Asbestos/*adverse effects ; History, 20th Century ; Humans ; Mesothelioma/epidemiology/*history ; Occupational Diseases/epidemiology/*history ; Pleural Neoplasms/epidemiology/*history ; }, } @article {pmid9372333, year = {1997}, author = {Takabe, K and Tsukada, Y and Shimizu, T and Takagiwa, J and Hirayama, M and Nakayama, M and Miura, H and Akabane, H and Takayama, S and Aida, S and Kimura, Y}, title = {Malignant lymphoma involving the penis following malignant pleural mesothelioma.}, journal = {Internal medicine (Tokyo, Japan)}, volume = {36}, number = {10}, pages = {712-715}, doi = {10.2169/internalmedicine.36.712}, pmid = {9372333}, issn = {0918-2918}, mesh = {Aged ; Antineoplastic Agents/therapeutic use ; Asbestos/adverse effects ; Biopsy ; Carcinogens/adverse effects ; Fatal Outcome ; Humans ; Lymphoma, B-Cell/drug therapy/etiology/*pathology ; Male ; Mesothelioma/chemically induced/drug therapy/*pathology ; Neoplasm Recurrence, Local ; Occupational Exposure/adverse effects ; Penile Neoplasms/drug therapy/etiology/*pathology ; Pleural Neoplasms/chemically induced/drug therapy/*pathology ; Radiography, Thoracic ; }, abstract = {A 74-year-old man who had been diagnosed with malignant mesothelioma developed malignant lymphoma of B-cell origin involving the penis. He had a history of occupational exposure to asbestos as a construction worker. The association of malignant mesothelioma with lymphoma is rare, and the possibility of asbestos exposure as a common etiology is discussed. The intense stimulation of B lymphocytes and decreased T lymphocyte activity in asbestos-exposed populations may result in development of B-cell malignancies. Though the relationship between asbestos exposure and malignant mesothelioma is firmly established, the relationship between asbestos exposure and lymphoma remains to be investigated.}, } @article {pmid9413169, year = {1997}, author = {Bagwe, AN and Kay, PH and Spagnolo, DV}, title = {Evidence that DNA methylation imbalance is not involved in the development of malignant mesothelioma.}, journal = {Anticancer research}, volume = {17}, number = {5A}, pages = {3341-3343}, pmid = {9413169}, issn = {0250-7005}, mesh = {Asbestos ; *DNA Methylation ; DNA, Neoplasm/metabolism ; Humans ; Mesothelioma/*genetics ; MyoD Protein/*genetics ; Myogenic Regulatory Factors/*genetics ; Pleural Neoplasms/genetics ; }, abstract = {Methylation dysregulation has been a consistent finding in various malignancies, particularly those where the pathogenetic mechanisms are unclear. In order to test the hypothesis that methylation imbalance may not be a feature of cancers where the aetiologic agent or process is known, we studied the methylation status of the myogenic genes Myf-3 and Myf-4 by Southern blotting in malignant mesothelioma, a cancer strongly associated with asbestos exposure. DNA samples obtained from controls and mesothelioma patients did not exhibit hypermethylation of Myf-3 and hypomethylation of Myf-4, as noted in malignant lymphomas. The methylation status of Myf-3 and Myf-4 in malignant mesothelioma was similar to that of non-malignant cells indicating that dysregulation of the DNA methylating machinery may not be involved in mesothelioma development. The present findings do not support the view that methylation imbalance is a consequence of neoplastic transformation, but indicate that it may be one of the early molecular events involved in the genesis of some cancers.}, } @article {pmid9409552, year = {1997}, author = {Broaddus, VC}, title = {Asbestos, the mesothelial cell and malignancy: a matter of life or death.}, journal = {American journal of respiratory cell and molecular biology}, volume = {17}, number = {6}, pages = {657-659}, doi = {10.1165/ajrcmb.17.6.f141}, pmid = {9409552}, issn = {1044-1549}, mesh = {Asbestos/*toxicity ; Carcinogens/*toxicity ; Cell Cycle/drug effects ; DNA Damage ; Epithelium/*drug effects/pathology ; Humans ; Mesothelioma/*chemically induced/genetics/pathology ; Mutation ; Tumor Suppressor Protein p53/genetics ; }, } @article {pmid9408534, year = {1998}, author = {Dumortier, P and De Vuyst, P and Rey, F and Boutin, C}, title = {RE main asbestos type in pleural mesothelioma.}, journal = {American journal of industrial medicine}, volume = {33}, number = {1}, pages = {94-96}, doi = {10.1002/(sici)1097-0274(199801)33:1<94::aid-ajim12>3.0.co;2-0}, pmid = {9408534}, issn = {0271-3586}, mesh = {Aged ; Aged, 80 and over ; Asbestos, Serpentine/analysis ; Humans ; Male ; Mesothelioma/*classification ; Pleural Neoplasms/*classification ; }, } @article {pmid9375529, year = {1997}, author = {McDonald, AD and Case, BW and Churg, A and Dufresne, A and Gibbs, GW and Sébastien, P and McDonald, JC}, title = {Mesothelioma in Quebec chrysotile miners and millers: epidemiology and aetiology.}, journal = {The Annals of occupational hygiene}, volume = {41}, number = {6}, pages = {707-719}, doi = {10.1016/S0003-4878(97)00020-3}, pmid = {9375529}, issn = {0003-4878}, mesh = {Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Asbestos, Amphibole/adverse effects ; Humans ; Logistic Models ; Lung/pathology ; Male ; Mesothelioma/chemically induced/*mortality ; Occupational Diseases/chemically induced/*mortality ; Odds Ratio ; Quebec/epidemiology ; }, abstract = {In a cohort of some 11,000 men born 1891-1920 and employed in the Quebec chrysotile production industry, including a small asbestos products factory, of 9780 men who survived into 1936, 8009 are known to have died before 1993, 38 probably from mesothelioma--33 in miners and millers and five in factory workers. Among the 5041 miners and millers at Thetford Mines, there had been 4125 deaths from all causes, including 25 (0.61%) from mesothelioma, a rate of 33.7 per 100,000 subject-years; the corresponding figures for the 4031 men at Asbestos were eight out of 3331 (0.24%, or 13.2 per 100,000 subject-years). At the factory in Asbestos, where all 708 employees were potentially exposed to crocidolite and/or amosite, there were 553 deaths, of which five (0.90%) were due to mesothelioma; the rate of 46.2 per 100,000 subject-years was 3.5 times higher than among the local miners and millers. Six of the 33 cases in miners and millers were in men employed from 2 to 5 years and who might have been exposed to asbestos elsewhere; otherwise, the 22 cases at Thetford were in men employed 20 years or more and the five at Asbestos for at least 30 years. The cases at Thetford were more common in miners than in millers, whereas those at. Asbestos were all in millers. Within Thetford Mines, case-referent analyses showed a substantially increased risk associated with years of employment in a circumscribed group of five mines (Area A), but not in a peripherally distributed group of ten mines (Area B); nor was the risk related to years employed at Asbestos, either at the mine and mill or at the factory. There was no indication that risks were affected by the level of dust exposure. A similar pattern in the prevalence of pleural calcification had been observed at Thetford Mines in the 1970s. These geographical differences, both within the Thetford region and between it and Asbestos, suggest that the explanation is mineralogical. Lung tissue analyses showed that the concentration of tremolite fibres was much higher in Area A than in Area B, a finding compatible with geological knowledge of the region. These findings, probably related to the far greater biopersistence of amphibole fibres than chrysotile, have important implications in the control of asbestos related disease and for wider aspects of fibre toxicology.}, } @article {pmid9375528, year = {1997}, author = {McDonald, JC and McDonald, AD}, title = {Chrysotile, tremolite and carcinogenicity.}, journal = {The Annals of occupational hygiene}, volume = {41}, number = {6}, pages = {699-705}, doi = {10.1016/S0003-4878(97)89350-7}, pmid = {9375528}, issn = {0003-4878}, mesh = {Aged ; Aged, 80 and over ; Asbestos, Amphibole/*adverse effects ; Asbestos, Serpentine/*adverse effects ; Case-Control Studies ; Coal Mining ; Humans ; Logistic Models ; Male ; Mesothelioma/*chemically induced/mortality ; Neoplasms/*chemically induced/mortality ; Occupational Diseases/*chemically induced/mortality ; Odds Ratio ; Quebec/epidemiology ; }, abstract = {It has been suspected for many years that amphibole fibres in the tremolite series, a low level contaminant of chrysotile asbestos, may contribute disproportionately to the incidence of mesothelioma and perhaps other exposure-related cancers. A cohort of some 11,000 Quebec chrysotile workers, 80% of whom have now died, provided the opportunity to examine this hypothesis further. An analysis was made of deaths from mesothelioma (21), cancers of the lung (262), larynx (15), stomach (99), and colon and rectum (76), in men employed by the largest company in Thetford Mines, with closely matched referents. Risks were estimated by logistic regression for these five cancers in two groups of mines--five mines located centrally and ten mines located peripherally; tremolite contamination had been demonstrated to be some four times higher in the former than in the latter. Odds ratios for work in the central mines were raised substantially and significantly for mesothelioma and lung cancer, but not for the gastric, intestinal or laryngeal cancer sites. In the peripheral mines, there was little or no evidence of increased risk for any of the five cancers. The hypothesis that, because of the difference in distribution of fibrous tremolite, cancer risks in the central area would be greater than in the periphery was thus substantiated. That the explanation may lie in the greater biopersistence of amphibole fibres than chrysotile is important in framing policies for the use and control of asbestos and is directly relevant to the selection of man-made mineral fibre substitutes.}, } @article {pmid9400747, year = {1997}, author = {Vu, VT and Lai, DY}, title = {Approaches to characterizing human health risks of exposure to fibers.}, journal = {Environmental health perspectives}, volume = {105 Suppl 5}, number = {Suppl 5}, pages = {1329-1336}, pmid = {9400747}, issn = {0091-6765}, mesh = {Air Pollution/*legislation & jurisprudence ; Animals ; Humans ; Inhalation Exposure/adverse effects ; Mineral Fibers/*toxicity ; Risk Assessment ; United States ; }, abstract = {Naturally occurring and man-made (synthetic) fibers of respirable sizes are substances that have been identified by the U.S. Environmental Protection Agency (U.S. EPA) as priority substances for risk reduction and pollution prevention under the Toxic Substances Control Act (TSCA). The health concern for respirable fibers is based on the link of occupational asbestos exposure and environmental erionite fiber exposure to the development of chronic respiratory diseases, including interstitial lung fibrosis, lung cancer, and mesothelioma in humans. There is also considerable laboratory evidence indicating that a variety of fibers of varying physical and chemical characteristics can elicit fibrogenic and carcinogenic effects in animals under certain exposure conditions. This paper discusses key scientific issues and major default assumptions and uncertainties pertaining to the risk assessment of inhaled fibers. This is followed by a description of the types of assessment performed by the U.S. EPA to support risk management actions of new fibers and existing fibers under TSCA. The scope and depth of these risk assessments, however, vary greatly depending on whether the substance under review is an existing or a new fiber, the purpose of the assessment, the availability of data, time, and resources, and the intended nature of regulatory action. In general, these risk assessments are of considerable uncertainty because health hazard and human exposure information is often incomplete for most fibers. Furthermore, how fibers cause diseases and what specific determinants are critical to fiber-induced toxicity and carcinogenicity are still not completely understood. Further research to improve our knowledge base in fiber toxicology and additional toxicity and exposure data gathering are needed to more accurately characterize the health risks of inhaled fibers.}, } @article {pmid9400733, year = {1997}, author = {Roller, M and Pott, F and Kamino, K and Althoff, GH and Bellmann, B}, title = {Dose-response relationship of fibrous dusts in intraperitoneal studies.}, journal = {Environmental health perspectives}, volume = {105 Suppl 5}, number = {Suppl 5}, pages = {1253-1256}, pmid = {9400733}, issn = {0091-6765}, mesh = {Animals ; Asbestos/administration & dosage/toxicity ; Carbon Compounds, Inorganic/administration & dosage/toxicity ; Carcinogens/administration & dosage/toxicity ; Dose-Response Relationship, Drug ; Dust/*adverse effects ; Female ; Injections, Intraperitoneal ; Lung Neoplasms/chemically induced/pathology ; Male ; Mesothelioma/chemically induced/pathology ; Mineral Fibers/*toxicity ; Particle Size ; Rats ; Rats, Wistar ; Silicon Compounds/administration & dosage/toxicity ; }, abstract = {The relationship between the number of fibers injected intraperitoneally and the occurrence of peritoneal mesotheliomas in rats was investigated using data from a series of carcinogenicity studies with several fibrous dusts. Based on observed tumor incidences ranging between 10 and 90%, the hypothesis of a common slope of dose-response relationships (parallel probit lines in probit analysis) cannot be rejected. In general, parallelism of probit lines is considered an indication of a common mode of action. Analysis of the shape of the dose-response relationship, with one apparent exception, shows virtually linear or superlinear behavior, i.e., from these data, there is no indication of a decrease in carcinogenic potency of an elementary carcinogenic unit at lower doses.}, } @article {pmid9400728, year = {1997}, author = {Hesterberg, TW and Axten, C and McConnell, EE and Oberdörster, G and Everitt, J and Miiller, WC and Chevalier, J and Chase, GR and Thevenaz, P}, title = {Chronic inhalation study of fiber glass and amosite asbestos in hamsters: twelve-month preliminary results.}, journal = {Environmental health perspectives}, volume = {105 Suppl 5}, number = {Suppl 5}, pages = {1223-1229}, pmid = {9400728}, issn = {0091-6765}, mesh = {Administration, Inhalation ; Aerosols ; Animals ; Asbestos, Amosite/administration & dosage/*toxicity ; Body Burden ; Body Weight/drug effects ; Cricetinae ; *Glass ; Lung/*metabolism/*pathology ; Male ; Mesocricetus ; Organ Size/drug effects ; Particle Size ; }, abstract = {The effects of chronic inhalation of glass fibers and amosite asbestos are currently under study in hamsters. The study includes 18 months of inhalation exposure followed by lifetime recovery. Syrian golden hamsters are exposed, nose only, for 6 hr/day, 5 day/week to size-selected test fibers: MMVF10a (Schuller 901 insulation glass); MMVF33 (Schuller 475 durable glass); amosite asbestos (three doses); or to filtered air (controls). Here we report interim results on airborne fiber characterization, lung fiber burden, and pathology (preliminary) through 12 months. Aerosolized test fibers averaged 15 to 20 microns in length and 0.5 to 1 micron in diameter. Target aerosol concentrations of World Health Organization (WHO) fibers (longer than 5 microns) were 250 fibers/cc for MMVF10a and MMVF33, and 25, 125, or 250 fibers/cc for amosite. WHO fiber lung burdens showed time-dependent and (for amosite) dose-dependent increases. After a 12-month exposure, lung burdens of fibers longer than 20 microns were greatest with amosite high and mid doses, similar for low-dose amosite and MMVF33, and smaller for MMVF10a. Biological responses of animals exposed for 12 months to MMVF10a were limited to nonspecific pulmonary inflammation. However, exposures to MMVF33 and each of three doses of amosite were associated with lung fibrosis and possible mesotheliomas (1 with MMVF33 and 2, 3, and 1 with amosite low, mid, and high doses, respectively). Pulmonary and pleural changes associated with amosite were qualitatively and quantitatively more severe than those associated with MMVF33. As of the 12-month time point, this study demonstrates that two different fiber glass compositions with similar fiber dimensions but different durabilities can have distinctly different effects on the hamster lung and pleura after inhalation exposure. (Preliminary tumor data through 18 months of exposure and 6 weeks of postexposure recovery became available as this manuscript went to press: No tumors were observed in the control or MMVF10a groups, and no additional tumors were observed in the MMVF33 group; however, a number of additional mesotheliomas were observed in the amosite groups.}, } @article {pmid9400723, year = {1997}, author = {Jagirdar, J and Lee, TC and Reibman, J and Gold, LI and Aston, C and Bégin, R and Rom, WN}, title = {Immunohistochemical localization of transforming growth factor beta isoforms in asbestos-related diseases.}, journal = {Environmental health perspectives}, volume = {105 Suppl 5}, number = {Suppl 5}, pages = {1197-1203}, pmid = {9400723}, issn = {0091-6765}, support = {MO1 RR00096/RR/NCRR NIH HHS/United States ; }, mesh = {Administration, Inhalation ; Aged ; Asbestos, Serpentine/adverse effects ; Asbestosis/*metabolism/*pathology ; Carcinogens/adverse effects ; Extracellular Matrix/metabolism ; Humans ; Immunohistochemistry ; Isomerism ; Lung Neoplasms/chemically induced/*metabolism/*pathology ; Mesothelioma/chemically induced/*metabolism/*pathology ; Pleura/pathology ; Transforming Growth Factor beta/chemistry/*metabolism ; }, abstract = {Transforming growth factor beta (TGF-beta), a multifunctional cytokine and growth factor, plays a key role in scarring and fibrotic processes because of its ability to induce extracellular matrix proteins and modulate the growth and immune function of many cell types. These effects are important in inflammatory disorders with fibrosis and cancer. The asbestos-related diseases are characterized by fibrosis in the lower respiratory tract and pleura and increased occurrence of lung cancer and mesothelioma. We performed immunohistochemistry with isoform-specific antibodies to the three TGF-beta isoforms on 16 autopsy lungs from Quebec, Canada, asbestos miners and millers. There was increased immunolocalization of all three TGF-beta isoforms in the fibrotic lesions of asbestosis and pleural fibrosis. The hyperplastic type II pneumocytes contained all three isoforms. By contrast, there was differential spatial immunostaining for the TGF-beta isoforms in malignant mesothelioma, with TGF-beta 1 in the stroma but TGF-beta 2 in the tumor cells. These data are consistent with an important role for TGF-beta in accumulation of extracellular matrix and cell proliferation in asbestos-related diseases.}, } @article {pmid9400715, year = {1997}, author = {Broaddus, VC and Yang, L and Scavo, LM and Ernst, JD and Boylan, AM}, title = {Crocidolite asbestos induces apoptosis of pleural mesothelial cells: role of reactive oxygen species and poly(ADP-ribosyl) polymerase.}, journal = {Environmental health perspectives}, volume = {105 Suppl 5}, number = {Suppl 5}, pages = {1147-1152}, pmid = {9400715}, issn = {0091-6765}, support = {HL24075/HL/NHLBI NIH HHS/United States ; KO8 ES00253/ES/NIEHS NIH HHS/United States ; R01 ESO6331/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Annexin A5/metabolism ; Apoptosis/*drug effects ; Asbestos, Crocidolite/*toxicity ; Carcinogens/*toxicity ; Catalase/metabolism ; Cell Nucleus/drug effects/metabolism ; DNA Fragmentation/drug effects ; Deferoxamine/pharmacology ; Epithelial Cells/drug effects/metabolism ; Iron Chelating Agents/pharmacology ; Membrane Lipids/metabolism ; Pleura/cytology/drug effects/*metabolism ; Poly(ADP-ribose) Polymerase Inhibitors ; Poly(ADP-ribose) Polymerases/*metabolism ; Rabbits ; Reactive Oxygen Species/*metabolism ; Superoxide Dismutase/metabolism ; }, abstract = {Mesothelial cells, the progenitor cells of the asbestos-induced tumor mesothelioma, are particularly sensitive to the toxic effects of asbestos, although the molecular mechanisms by which asbestos induces injury in mesothelial cells are not known. We asked whether asbestos induced apoptosis in mesothelial cells and whether reactive oxygen species were important. Rabbit pleural mesothelial cells were exposed to crocidolite asbestos or control particles (1-10 micrograms/cm2) over 24 hr and evaluated for oligonucleosomal DNA fragmentation, loss of membrane phospholipid asymmetry, and nuclear condensation. Asbestos fibers, not control particles, induced apoptosis in mesothelial cells by all assays. Induction of apoptosis was dose dependent; crocidolite (5 micrograms/cm2) induced apoptosis (15.0 +/- 1.1%, mean +/- SE; n = 12) versus control particles (< 4%), as measured by appearance of nuclear condensation. Apoptosis induced by asbestos, but not by actinomycin D, was inhibited by extracellular catalase, superoxide dismutase in the presence of catalase, hypoxia (8% oxygen), deferoxamine, and 3-aminobenzamide (an inhibitor of the nuclear enzyme, poly(adenosine diphosphate-ribosyl) polymerase). We conclude that asbestos induces apoptosis in mesothelial cells via reactive oxygen species. We speculate that escape from this pathway could allow the abnormal survival of mesothelial cells with asbestos-induced mutations.}, } @article {pmid9400707, year = {1997}, author = {Unfried, K and Roller, M and Pott, F and Friemann, J and Dehnen, W}, title = {Fiber-specific molecular features of tumors induced in rat peritoneum.}, journal = {Environmental health perspectives}, volume = {105 Suppl 5}, number = {Suppl 5}, pages = {1103-1108}, pmid = {9400707}, issn = {0091-6765}, mesh = {Abdominal Neoplasms/chemically induced/pathology ; Animals ; Asbestos, Crocidolite/chemistry/toxicity ; Benzo(a)pyrene/chemistry/toxicity ; Carcinogens/administration & dosage/*chemistry/*toxicity ; Electrophoresis, Polyacrylamide Gel ; Genes, p53/drug effects/genetics ; Genetic Markers ; Injections, Intraperitoneal ; Mesothelioma/*chemically induced/*pathology ; Mineral Fibers/*analysis/*toxicity ; Peritoneal Neoplasms/*chemically induced/*pathology ; Point Mutation/genetics ; Polymerase Chain Reaction ; RNA, Messenger/biosynthesis/genetics ; RNA, Neoplasm/biosynthesis/isolation & purification ; Rats ; Rats, Wistar ; }, abstract = {Molecular markers such as mutational spectra or mRNA expression patterns may give some indication of the mechanisms of carcinogenesis induced by fibers and other carcinogens. In our study, tumors were induced by application of crocidolite asbestos or benzo[a]pyrene (B[a]P) to rat peritoneum. DNA and RNA of these tumors were subjected to analysis of point mutations and to investigation of mRNA expression patterns. With both assays we found typical features depending on the type of carcinogen applied. The analysis of point mutations in the tumor suppressor gene p53 revealed mutations in the B[a]P-induced tumors. However, in the tumors induced by crocidolite asbestos that were of the same tumor type as those induced by B[a]P, mutations in p53 were not detectable. Every mutation detected on the DNA level causes an amino acid substitution within one of the functional domains of the tumor suppressor protein. Therefore, these mutations seem to be of biological relevance for tumor progression and indicate a difference in the carcinogenesis regarding the type of the carcinogenic substance. An additional specificity of crocidolite-induced tumors was detectable by analyzing the mRNA expression of the tumor suppressor gene WT1, which is known to be expressed in human mesothelial and mesothelioma cells. A relatively high amount of WT1 mRNA was measured by quantitative competitive reverse transcription-polymerase using RNA extracted from crocidolite-induced tumors. However, WT1 seems to be expressed on a rather low level in tumors induced by B[a]P.}, } @article {pmid9400702, year = {1997}, author = {Marsella, JM and Liu, BL and Vaslet, CA and Kane, AB}, title = {Susceptibility of p53-deficient mice to induction of mesothelioma by crocidolite asbestos fibers.}, journal = {Environmental health perspectives}, volume = {105 Suppl 5}, number = {Suppl 5}, pages = {1069-1072}, pmid = {9400702}, issn = {0091-6765}, support = {R01 ES03721/ES/NIEHS NIH HHS/United States ; R01 ES05712/ES/NIEHS NIH HHS/United States ; }, mesh = {Alleles ; Animals ; Antineoplastic Agents, Phytogenic/pharmacology ; Apoptosis/drug effects ; Asbestos, Crocidolite/*toxicity ; Camptothecin/pharmacology ; Carcinogens/*toxicity ; Chromosomes/drug effects/ultrastructure ; Genes, p53/genetics ; Lung Neoplasms/*chemically induced/*genetics ; Mesothelioma/*chemically induced/*genetics ; Mice ; Mice, Transgenic ; Tumor Suppressor Protein p53/biosynthesis/*deficiency/genetics ; }, abstract = {Exposure of mesothelial cells to asbestos fibers in vitro has been shown to induce DNA damage mediated by oxidants. An early cellular response to DNA damage is increased expression of the p53 protein. This protein induces transcription of genes that activate cell cycle checkpoints or induce apoptosis. A murine mesothelial cell line that spontaneously acquired a point mutation in the p53 gene shows increased sensitivity to DNA damage induced by crocidolite asbestos fibers. It is hypothesized that p53-deficient mice will show increased sensitivity to the genotoxic effects of asbestos and accelerated development of malignant mesotheliomas.}, } @article {pmid9400697, year = {1997}, author = {Gulumian, M and Nkosibomvu, ZL and Channa, K and Pollak, H}, title = {Can microwave radiation at high temperatures reduce the toxicity of fibrous crocidolite asbestos?.}, journal = {Environmental health perspectives}, volume = {105 Suppl 5}, number = {Suppl 5}, pages = {1041-1044}, pmid = {9400697}, issn = {0091-6765}, mesh = {Aldehydes/chemistry/radiation effects ; Asbestos, Crocidolite/chemistry/*radiation effects ; Hot Temperature ; Hydrogen Peroxide/chemistry/radiation effects ; Iron/chemistry/radiation effects ; *Microwaves ; Oxidation-Reduction ; Spectroscopy, Mossbauer ; }, abstract = {Exposure of animals and humans to crocidolite asbestos fibers produces fibrosis and two types of cancers: bronchogenic carcinoma and mesothelioma. It is therefore desirable to reduce toxicity of these fibers without affecting their other characteristics. In this study, commercial crocidolite asbestos fibers were radiated with microwave radiation at different temperatures. Radiated fibers and nonradiated original fibers were then studied by Mössbauer spectroscopy to quantify the amount of ferric and ferrous ions present at structurally different sites in each crocidolite sample. They were also studied for their ability to initiate the peroxidation of linoleic acid to assess the effect of radiation on this process. Results showed that microwave radiation reduced the total Fe2+/Fe3+ ratio. This reduction produced a concomitant decrease in the ability of the radiated samples to peroxidize linoleic acid.}, } @article {pmid9400682, year = {1997}, author = {Mizuki, M and Yukishige, K and Abe, Y and Tsuda, T}, title = {A case of malignant pleural mesothelioma following exposure to atomic radiation in Nagasaki.}, journal = {Respirology (Carlton, Vic.)}, volume = {2}, number = {3}, pages = {201-205}, doi = {10.1111/j.1440-1843.1997.tb00079.x}, pmid = {9400682}, issn = {1323-7799}, mesh = {Aged ; Dose-Response Relationship, Radiation ; Environmental Exposure/*adverse effects ; Follow-Up Studies ; Hemothorax/etiology/surgery ; Humans ; Japan ; Male ; Mesothelioma/*etiology/pathology/surgery ; Neoplasms, Radiation-Induced/*etiology/pathology/surgery ; *Nuclear Warfare ; Pleural Neoplasms/*etiology/pathology/surgery ; }, abstract = {We report the case of a 75-year-old Japanese man who developed malignant mesothelioma in the left hemithorax 50 years after the dropping of the atomic bomb on Nagasaki in 1945. This may be the first reported case of malignant mesothelioma following exposure to atomic radiation. Asbestos is the leading cause of malignant mesothelioma, but radiation therapy is the primary non-asbestos-related cause. In the case of radiation therapy, the interval between exposure and the occurrence of malignant mesothelioma tends to be many years. This patient was at a high risk of malignant mesothelioma as he had been exposed to radiation from the atomic bomb and may also have had a history of asbestos exposure at the munitions factory where he was employed as a shipbuilder for 2 years. It has been suggested that combined exposure to atomic radiation and asbestos is associated with an increased incidence of malignant mesothelioma. If thickening of the pleura or pleural effusion is found in atomic bomb survivors, malignant mesothelioma should be considered as one of the options in the differential diagnosis, even although the atomic bomb attacks occurred several decades ago.}, } @article {pmid9365233, year = {1997}, author = {Carbone, M and Rizzo, P and Pass, HI}, title = {Simian virus 40, poliovaccines and human tumors: a review of recent developments.}, journal = {Oncogene}, volume = {15}, number = {16}, pages = {1877-1888}, doi = {10.1038/sj.onc.1201375}, pmid = {9365233}, issn = {0950-9232}, support = {CA-74283-01/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Drug Contamination ; Humans ; Neoplasms/epidemiology/*virology ; *Poliovirus Vaccine, Inactivated ; Simian virus 40/*genetics ; }, abstract = {Recently, wild-type SV40 and/or DNA sequences indistinguishable from SV40 have been detected in specific types of human tumors: ependymoma and choroid plexus tumors, mesothelioma, osteosarcoma and sarcoma. The same tumor types will develop in hamsters after injection with SV40. These findings are interesting in themselves for they could shed light on the pathogenesis of these tumors. These findings also have public health implications. SV40 was found to have contaminated the poliovaccines and the adenovaccines from 1955 until 1963, therefore resulting in the inadvertent injection of millions of people with this tumor virus. Moreover, our society pays a high cost for asbestos causality, a carcinogen associated with the development of mesothelioma. In addition to asbestos, the potential impact of finding another possible cause for mesothelioma (i.e., SV40), as well as the possible pathogenic role of the contaminated poliovaccines, has generated considerable public interest and concern. To discuss these recent findings, the NIH (National Institutes of Health) and the FDA (Food and Drug Administration), organized an International Conference at the NIH, Bethesda, MD, January 27-28, 1997. The association of SV40 with human mesothelioma was also discussed in a special session at the IV International Mesothelioma Conference that was held at the University of Pennsylvania, Philadelphia, PA, May 13-16, 1997. The purpose of this review is to summarize data, from the discovery of the contaminated poliovaccines, to the most recent findings presented at the meetings in Bethesda and Philadelphia, to discuss technical and other problems associated with this research, and the potential for using these findings to develop new diagnostic and therapeutic approaches for SV40-associated malignancies.}, } @article {pmid9356317, year = {1997}, author = {Wylie, AG and Skinner, HC and Marsh, J and Snyder, H and Garzione, C and Hodkinson, D and Winters, R and Mossman, BT}, title = {Mineralogical features associated with cytotoxic and proliferative effects of fibrous talc and asbestos on rodent tracheal epithelial and pleural mesothelial cells.}, journal = {Toxicology and applied pharmacology}, volume = {147}, number = {1}, pages = {143-150}, doi = {10.1006/taap.1997.8276}, pmid = {9356317}, issn = {0041-008X}, support = {R01ES06499/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Asbestos/chemistry/*toxicity ; Carcinogens/*toxicity ; Cells, Cultured ; Cricetinae ; Epithelial Cells/drug effects/pathology ; Epithelium/drug effects/pathology ; Male ; Mesothelioma/etiology ; Microscopy, Electron ; Microscopy, Electron, Scanning ; Particle Size ; Pleural Neoplasms/etiology ; Rats ; Rats, Inbred F344 ; Surface Properties ; Talc/chemistry/*toxicity ; Trachea/*drug effects ; X-Ray Diffraction ; }, abstract = {Inhalation of asbestos fibers causes cell damage and increases in cell proliferation in various cell types of the lung and pleura in vivo. By using a colony-forming efficiency (CFE) assay, the cytotoxicity and proliferative potential of three mineral samples containing various proportions of fibrous talc were compared to NIEHS samples of crocidolite and chrysotile asbestos in cell types giving rise to tracheobronchial carcinomas, i.e., hamster tracheal epithelial (HTE) cells, and mesotheliomas, i.e., rat pleural mesothelial (RPM) cells. Characterization of mineralogical composition, surface area, and size distributions as well as proportions of fibers in all mineral samples allowed examination of data by various dose parameters including equal weight concentrations, numbers of fibers >5 micron in length, and equivalent surface areas. Exposure to samples of asbestos caused increased numbers of colonies of HTE cells, an indication of proliferative potential, but fibrous talc did not. RPMs did not exhibit increased CFE in response to either asbestos or talc samples. Decreased numbers of colonies, an indication of cytotoxicity, were observed in both cell types and were more striking at lower weight concentrations of asbestos in comparison to talc samples. However, all samples of fibrous minerals produced comparable dose-response effects when dose was measured as numbers of fibers greater than 5 micron or surface area. The unique proliferative response of HTE cells to asbestos could not be explained by differences in fiber dimensions or surface areas, indicating an important role of mineralogical composition rather than size of fibers.}, } @article {pmid9356192, year = {1997}, author = {Berry, M}, title = {Mesothelioma incidence and community asbestos exposure.}, journal = {Environmental research}, volume = {75}, number = {1}, pages = {34-40}, doi = {10.1006/enrs.1997.3770}, pmid = {9356192}, issn = {0013-9351}, mesh = {Asbestos/*poisoning ; Carcinogens ; Female ; Humans ; Incidence ; Male ; Mesothelioma/chemically induced/*epidemiology ; New Jersey/epidemiology ; Population Surveillance ; Registries ; }, abstract = {This study evaluates the environmental, nonoccupational component of mesothelioma incidence among persons living in Manville, Somerset County, New Jersey, the location of the largest asbestos manufacturing plant in North America. Prior to removal of occupational cases, residents of Manville had an average annual (1979-1990) mesothelioma rate of 636 male cases and 96 female cases per million population, about 25 times higher than average state rates. Somerset County had 143 diagnosed mesothelioma cases reported to the population-based. New Jersey State Cancer Registry from 1979 through 1990. Cases were removed from the analysis when their "usual employment" was reported as being at the asbestos plant, as evidenced through union lists or occupational information from either the Cancer Registry or mortality records. Standardized incidence ratios (SIRs) were computed for residents of Manville and Somerset County (less the Manville population) by sex. New Jersey mesothelioma rates less the Somerset County contribution, 1979-1990, were used to generate the expected number of cases. The SIRs for Manville males and females were respectively 10.1 [95% confidence interval (CI): 5.8-16.4] and 22.4 (95% CI: 9.7-44.2). Male and female Somerset County mesothelioma incidence rates were 1.9 (95% CI: 1.4-2.5) and 2.0 (95% CI: 1.0-3.6). This record-based approach demonstrates a strong relationship between past asbestos exposure from living in Manville and eventual development of mesothelioma. The use of methods in this study may be helpful in evaluating hazards of other known occupational carcinogens found in community settings.}, } @article {pmid9327067, year = {1997}, author = {Bianchi, C and Brollo, A and Ramani, L and Zuch, C}, title = {Pleural plaques as risk indicators for malignant pleural mesothelioma: a necropsy-based study.}, journal = {American journal of industrial medicine}, volume = {32}, number = {5}, pages = {445-449}, doi = {10.1002/(sici)1097-0274(199711)32:5<445::aid-ajim3>3.0.co;2-r}, pmid = {9327067}, issn = {0271-3586}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Comorbidity ; Female ; Humans ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology/pathology ; Middle Aged ; Occupational Diseases/*epidemiology ; Odds Ratio ; Pleural Diseases/chemically induced/*epidemiology ; Pleural Neoplasms/*epidemiology/pathology ; Prevalence ; Risk Factors ; Ships ; Time Factors ; }, abstract = {Pleural plaque is recognized as a reliable marker of previous exposure to asbestos. However, it is controversial whether pleural plaque is a risk indicator for asbestos-related malignancies. In the present study, the thoracic cavities were examined for pleural plaques in 3,005 necropsies performed at the Monfalcone Hospital in people aged 15 years or older. Plaques were classified into three classes: 1, small (plaques measuring 1-4 cm in major diameter); 3, large (plaques involving a major part of a hemithorax); and 2, moderate (intermediate conditions). The prevalences of pleural plaques were 70.9% among men, and 24.0% among women. The prevalences of plaques (total plaques, various classes) among subjects with pleural mesothelioma were compared with those observed in the remaining cases. The series included 92 subjects with malignant pleural mesothelioma (82 men and 10 women). Mesothelioma cases showed higher prevalences of total plaques as well as higher prevalences of classes 1, 2, and 3, when compared with controls. These differences reached the statistical significance for total plaques, and classes 2, 3. The present data are consistent with the idea that pleural plaque is a risk indicator for pleural mesothelioma.}, } @article {pmid9307196, year = {1997}, author = {Neugut, AI and Ahsan, H and Antman, KH}, title = {Incidence of malignant pleural mesothelioma after thoracic radiotherapy.}, journal = {Cancer}, volume = {80}, number = {5}, pages = {948-950}, doi = {10.1002/(sici)1097-0142(19970901)80:5<948::aid-cncr17>3.0.co;2-w}, pmid = {9307196}, issn = {0008-543X}, mesh = {Breast Neoplasms/*radiotherapy ; Cohort Studies ; Female ; Hodgkin Disease/*radiotherapy ; Humans ; Incidence ; Male ; Mesothelioma/epidemiology/*etiology ; Neoplasms, Radiation-Induced/epidemiology/*etiology ; Neoplasms, Second Primary/epidemiology/*etiology ; Pleural Neoplasms/epidemiology/*etiology ; Radiotherapy/adverse effects ; Retrospective Studies ; Risk ; SEER Program ; Thorax ; United States/epidemiology ; }, abstract = {BACKGROUND: Although usually associated with asbestos exposure, a number of case reports have noted the occurrence of malignant pleural mesothelioma in patients who received radiotherapy (RT) to the thorax.

METHODS: The authors performed a retrospective cohort study utilizing 251,750 women registered with breast carcinoma in the Surveillance, Epidemiology, and End Results Program of the U.S. National Cancer Institute from 1973-1993, 24.8% of whom received RT as part of their initial management, and 13,743 people with Hodgkin's disease, 50.6% of whom received RT as part of their initial management.

RESULTS: Six cases of malignant pleural mesothelioma were found: two in breast carcinoma patients treated with RT and four found in women not treated with RT. No cases occurred in the patients with Hodgkin's disease. The overall estimated relative risk for malignant pleural mesothelioma after RT was 1.56 (95% confidence interval, 0.18-5.63).

CONCLUSIONS: To the authors' knowledge, this is the first controlled study to investigate thoracic radiation exposure and malignant pleural mesothelioma, and no association was found.}, } @article {pmid9543762, year = {1997}, author = {Schouten, LJ}, title = {[Increasing incidence of mesothelioma in the future due to occupational exposure to asbestos in the past].}, journal = {Nederlands tijdschrift voor geneeskunde}, volume = {141}, number = {32}, pages = {1584-1585}, pmid = {9543762}, issn = {0028-2162}, mesh = {Asbestos/*toxicity ; Humans ; Mesothelioma/*etiology/mortality ; Netherlands/epidemiology ; *Occupational Exposure ; Pleural Neoplasms/*etiology/mortality ; }, } @article {pmid9381428, year = {1997}, author = {Stenton, SC}, title = {Asbestos, Simian virus 40 and malignant mesothelioma.}, journal = {Thorax}, volume = {52 Suppl 3}, number = {Suppl 3}, pages = {S52-7}, pmid = {9381428}, issn = {0040-6376}, mesh = {Asbestos, Amphibole/*adverse effects ; Cell Transformation, Neoplastic ; Cell Transformation, Viral ; Cocarcinogenesis ; Humans ; Mesothelioma/etiology/*virology ; Papillomavirus Infections/*complications ; Pleural Neoplasms/etiology/*virology ; Simian virus 40/*isolation & purification ; Tumor Virus Infections/*complications ; }, } @article {pmid9322824, year = {1997}, author = {}, title = {Asbestos, asbestosis, and cancer: the Helsinki criteria for diagnosis and attribution.}, journal = {Scandinavian journal of work, environment & health}, volume = {23}, number = {4}, pages = {311-316}, pmid = {9322824}, issn = {0355-3140}, mesh = {Asbestos/*adverse effects ; Asbestosis/*diagnosis ; Finland ; Humans ; Lung Neoplasms/etiology ; Mass Screening ; Mesothelioma/etiology ; Occupational Diseases/*etiology/prevention & control ; Occupational Exposure ; Pleural Diseases/etiology ; Respiratory Tract Diseases/*etiology/prevention & control ; Risk Assessment ; }, } @article {pmid9322817, year = {1997}, author = {Karjalainen, A and Pukkala, E and Mattson, K and Tammilehto, L and Vainio, H}, title = {Trends in mesothelioma incidence and occupational mesotheliomas in Finland in 1960-1995.}, journal = {Scandinavian journal of work, environment & health}, volume = {23}, number = {4}, pages = {266-270}, doi = {10.5271/sjweh.219}, pmid = {9322817}, issn = {0355-3140}, mesh = {Aged ; Female ; Finland/epidemiology ; Humans ; Incidence ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Occupational Diseases/*epidemiology ; Peritoneal Neoplasms/*epidemiology ; Pleural Neoplasms/*epidemiology ; }, abstract = {OBJECTIVES: The study analyzed the recent trend in the incidence of mesothelioma in Finland and evaluated the coverage of reporting work-related mesothelioma.

METHODS: The incidence of mesothelioma in 1960-1995 was retrieved from the Finnish Cancer Registry, and the number of asbestos-associated work-related mesotheliomas were taken from the Finnish Register of Occupational Diseases.

RESULTS: The annual number of mesotheliomas increased rapidly in 1975-1990. In the 1990s, the age-adjusted incidence remained relatively stable for Finnish men. The annual number of cases still increased among men over 65 years of age, but decreased slightly among men under 55 years of age and among women. About 35 annual cases were diagnosed among men and 10-15 among women in the mid-1990s. The reporting of work-related mesotheliomas improved during the Finnish asbestos program in 1987-1992. In 1993-1995 about 30 annual cases (ie, about 90% of all pleural and 50% of the peritoneal mesotheliomas in men) were reported to be work-related.

CONCLUSIONS: The increasing trend in the incidence of mesothelioma in Finland has slowed down in the 1990s, and the maximum of asbestos-related cases in the early 2000s will probably be clearly less than the 100 annual cases estimated in the early 1990s. If the observed trend continues up to 2010, about 40-50 cases among men and 10-20 among women will then be diagnosed annually. Altogether 40-50 of these cases would be related to occupational asbestos exposure.}, } @article {pmid9260780, year = {1997}, author = {Kawai, A and Nagasaka, Y and Muraki, M and Fukuoka, M and Satou, T and Kimura, M and Hashimoto, S}, title = {Brain metastasis in malignant pleural mesothelioma.}, journal = {Internal medicine (Tokyo, Japan)}, volume = {36}, number = {8}, pages = {591-594}, doi = {10.2169/internalmedicine.36.591}, pmid = {9260780}, issn = {0918-2918}, mesh = {Adrenal Gland Neoplasms/pathology/secondary ; Asbestos/chemistry ; Brain Neoplasms/*pathology/*secondary ; Fatal Outcome ; Humans ; Lung/chemistry/pathology ; Male ; Mesothelioma/*pathology/*secondary ; Middle Aged ; Pleural Effusion, Malignant/*pathology ; }, abstract = {A 55-year-old male who had a remote history of occupational asbestos exposure consulted us because of chest pain. Chest X-ray revealed diffuse pleural thickening and pleural effusion on the right. A diagnosis of malignant mesothelioma, biphasic type was made by needle pleural biopsy. Fourteen months later, the patient died of brain metastasis. At autopsy, malignant mesothelioma of the pleura with metastasis to the brain and bilateral adrenal glands was observed. Brain metastases proven by autopsy are rare in cases of malignant mesothelioma. The ferruginous body count in the lung tissue was 16 per gram of wet weight.}, } @article {pmid9256284, year = {1997}, author = {Carbone, M and Rizzo, P and Grimley, PM and Procopio, A and Mew, DJ and Shridhar, V and de Bartolomeis, A and Esposito, V and Giuliano, MT and Steinberg, SM and Levine, AS and Giordano, A and Pass, HI}, title = {Simian virus-40 large-T antigen binds p53 in human mesotheliomas.}, journal = {Nature medicine}, volume = {3}, number = {8}, pages = {908-912}, doi = {10.1038/nm0897-908}, pmid = {9256284}, issn = {1078-8956}, support = {CA 60999-01A1/CA/NCI NIH HHS/United States ; CA 77220-01A1/CA/NCI NIH HHS/United States ; NS 36466-01/NS/NINDS NIH HHS/United States ; }, mesh = {Antigens, Polyomavirus Transforming/*metabolism ; Gene Expression Regulation, Neoplastic ; Genes, p53 ; Humans ; Immunohistochemistry ; Mesothelioma/genetics/*metabolism/pathology ; Mutation ; Pleural Neoplasms/*metabolism/pathology ; Protein Binding ; Simian virus 40/*immunology ; Tumor Cells, Cultured ; Tumor Suppressor Protein p53/genetics/*metabolism ; }, abstract = {We found that simian virus 40 (SV40) induces mesotheliomas in hamsters and that 60% of human mesotheliomas contain and express SV40 sequences, results now confirmed by others [ref. 3-5, and presentations by D. Griffiths & R. Weiss, F. Galateau-SallE, and H.I.P. at "Simian virus 40: A possible human polyoma virus," NIH workshop, 27-28 January 1997, Bethesda, MD (transcript available through SAG Corp., Washington, DC 20008)]. Mesothelioma, an aggressive malignancy resistant to therapy, originates from the serosal lining of the pleural, pericardial and peritoneal cavities. The incidence of mesothelioma continues to increase worldwide because of exposure to crocidolite asbestos. However, at least 20% of mesotheliomas in the United States are not associated with asbestos exposure, and only a minority of people exposed to high concentrations of asbestos develop mesothelioma. Thus, other carcinogens may induce mesothelioma in individuals not exposed to asbestos, and/or may render particular individuals more susceptible to the carcinogenic effect of asbestos. We investigated whether the expression of the SV40 large T-antigen (Tag) interferes with the normal expression of the tumor suppressor gene p53 in human mesotheliomas. We found that SV40 Tag retains its ability to bind and to inactivate p53, a cellular protein that when normally expressed plays an important role in suppressing tumor growth and in inducing sensitivity to therapy. Our findings do not establish a cause-and-effect relation, but indicate that the possibility that SV40 contributes to the development of human mesotheliomas should be carefully investigated.}, } @article {pmid9242432, year = {1997}, author = {Fung, H and Quinlan, TR and Janssen, YM and Timblin, CR and Marsh, JP and Heintz, NH and Taatjes, DJ and Vacek, P and Jaken, S and Mossman, BT}, title = {Inhibition of protein kinase C prevents asbestos-induced c-fos and c-jun proto-oncogene expression in mesothelial cells.}, journal = {Cancer research}, volume = {57}, number = {15}, pages = {3101-3105}, pmid = {9242432}, issn = {0008-5472}, support = {ES 06499/ES/NIEHS NIH HHS/United States ; HL 39469/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Asbestos/*pharmacology ; Benzoquinones ; Epithelium/drug effects/*enzymology ; Gene Expression ; Isoenzymes ; Lactams, Macrocyclic ; Naphthalenes/pharmacology ; Phorbol 12,13-Dibutyrate/pharmacology ; Protein Kinase C/*physiology ; Protein-Tyrosine Kinases/antagonists & inhibitors/metabolism ; Proto-Oncogene Proteins c-fos/genetics/*metabolism ; Proto-Oncogene Proteins c-jun/genetics/*metabolism ; Quinones/pharmacology ; RNA, Messenger/analysis ; Rats ; Rats, Inbred F344 ; Rifabutin/analogs & derivatives ; Time Factors ; }, abstract = {Asbestos and the phorbol ester tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), increase c-fos and c-jun mRNA levels and AP-1 DNA binding activity in rat pleural mesothelial (RPM) cells, a target cell of asbestos-induced mesotheliomas (N. H. Heintz et al., Proc. Natl. Acad. Sci. USA, 90: 3299-3303, 1993). Because protein kinase C (PKC) is the intracellular receptor of phorbol ester tumor promoters and asbestos is a putative tumor promoter in the respiratory tract, we hypothesized that PKC might play a critical role in asbestos-induced cell signaling pathways associated with regulation of proto-oncogenes. Using a panel of PKC antibodies, we identified PKC alpha as the major PKC isozyme in RPM cells. We then pretreated cells with phorbol ester dibutyrate to down-modulate PKC or with calphostin C, a specific PKC inhibitor, to determine if depletion of PKC alpha could block asbestos-induced c-fos/c-jun expression. Quantitation of Northern blots showed that fiber-associated c-fos/c-jun mRNA levels were significantly lower either after PKC alpha down-modulation or pretreatment with calphostin C. In addition, to determine whether tyrosine kinases also were involved in proto-oncogene activation by asbestos, tyrphostin AG82 or herbimycin A was added to RPM cells before exposure to asbestos. These inhibitors decreased crocidolite-induced c-fos but not c-jun levels, suggesting that tyrosine kinases have different regulatory roles in asbestos-induced c-fos versus c-jun signaling pathways. The ability to block induction of asbestos-induced proto-oncogene expression using pharmacological intervention may be important in prevention and treatment of asbestos-induced proliferative diseases including lung cancers, mesothelioma, and pulmonary fibrosis.}, } @article {pmid9265327, year = {1997}, author = {Kjaergaard, J and Michelsen, EV}, title = {[Malignant mesothelioma: incidence, survival and relative risks in selected municipalities 1943-1992].}, journal = {Ugeskrift for laeger}, volume = {159}, number = {31}, pages = {4756-4761}, pmid = {9265327}, issn = {0041-5782}, mesh = {Adult ; Aged ; Denmark/epidemiology ; Female ; Humans ; Incidence ; Male ; Mesothelioma/*epidemiology/mortality ; Middle Aged ; Pericardium/pathology ; Pleural Neoplasms/*epidemiology/metabolism ; Registries ; Risk Factors ; Survival Rate ; }, abstract = {The development in incidence rates and survival in Denmark, and the rate-ratio in selected municipalities that had industries utilizing asbestos was studied in 1865 cases of malignant mesothelioma identified in the Danish Cancer Registry 1943-1992. For men a steady increase in the incidence to 1.6 per 100,000 personyears in 1992 was found, while the rate for women decreased to 0.28 per 100,000 personyears. Age-specific incidence rates were highest for the older age-groups. An unexplained difference in the distribution of pleural and peritoneal cancers was seen between men and women. The average survival was 6.9 months for men and 7.8 for women and had not changed during the period of observation. The average rate-ratio for the selected municipalities was 1.97 (95% confidence intervals: 1.73-2.24) for men and 1.35 (1.08-1.69) for women. Improvements in working conditions in terms of minimizing asbestos exposure were introduced in 1980. Considering the latency period from exposure to diagnosis of 25-30 years, the impact of this measure on the rate of incidence cannot be expected before the year 2000.}, } @article {pmid9349372, year = {1997}, author = {Hasleton, PS}, title = {The diagnosis of pleural disease.}, journal = {British journal of hospital medicine}, volume = {58}, number = {2-3}, pages = {85-89}, pmid = {9349372}, issn = {0007-1064}, mesh = {Asbestos/adverse effects ; Biopsy, Needle ; Collagen Diseases/complications ; Humans ; Lung Neoplasms/*complications ; Mesothelioma/*complications ; Pleural Diseases/*etiology ; Pleural Effusion/etiology ; Thoracoscopy ; }, } @article {pmid9611294, year = {1997}, author = {D'Albuquerque, LA and Padilla, JM and Rodrigues, AL and Souza, MV and Quireze Júnior, C and Meniconi, MT and Copstein, JL and dos Santos Júnior, ED and de Melo, CR and Santo, GC and de Oliveira e Silva, A}, title = {[Diffuse primary malignant mesothelioma in abdominal cavity].}, journal = {Arquivos de gastroenterologia}, volume = {34}, number = {3}, pages = {163-168}, pmid = {9611294}, issn = {0004-2803}, mesh = {Aged ; Asbestos/adverse effects ; Carcinogens/adverse effects ; Humans ; Magnetic Resonance Imaging ; Male ; Mesothelioma/chemically induced/*diagnosis ; Middle Aged ; Peritoneal Neoplasms/chemically induced/*diagnosis ; Tomography, X-Ray Computed ; }, abstract = {Two cases of diffuse malignant mesothelioma of abdominal cavity were analysed. These tumors arise from the peritoneum and are also found in the parietal and visceral pleura, pericardium and in vaginal tunic. All of them, infra or supra-diaphragmatic, are associated with asbestos exposure in at least 80% of cases. It is difficult to explain how inhaled asbestos induces peritoneal neoplasms. This aspects become very important in the diagnostic, basically why it is done at laparotomy or laparoscopy. When was proceed the biopsy of the lesions, and occasionally by identification of malignant mesothelial cells in ascitic fluid. In this two cases exposed considerations about the advanced phase of diagnostic are made, the diagnostic was performed in the majority of the collected cells, showing the advanced stage of the disease. At that time of diagnosis we observed poor evolution. We call attention to the importance of precancer diagnosis, the best chance to treatment options, always based on surgical resections, radiation or chemotherapy alone or combined. If the radical surgery is not possible, this patients must be treated by chemotherapy or radiotherapy, defined after complete staging of the disease.}, } @article {pmid9497555, year = {1997}, author = {de Capitani, EM and Metze, K and Frazato Júnior, C and Altemani, AM and Zambom, L and Toro, IF and Bagatin, E}, title = {[Malignant mesothelioma of the pleura with etiological association to asbestos: report of 3 clinical cases].}, journal = {Revista da Associacao Medica Brasileira (1992)}, volume = {43}, number = {3}, pages = {265-272}, pmid = {9497555}, issn = {0104-4230}, mesh = {Adult ; Asbestos/*adverse effects ; Carcinogens/*adverse effects ; Humans ; Male ; Mesothelioma/diagnosis/*etiology ; Middle Aged ; Pleural Neoplasms/diagnosis/*etiology ; }, abstract = {UNLABELLED: Diffuse Malign Mesotheliomas (DMM) has a low background prevalence. High incidences of this tumor have been related to asbestos exposure in the past.

PURPOSE: To describe and discuss three clinical cases treated in our hospital, in which precise histopathologic diagnosis was made, and detailed occupational and environmental histories were taken, trying to identify in their past some kind of asbestos exposure.

METHODS: Three cases of DMM are described. Diagnosis was confirmed by histochemical analysis and electronmicroscopy. Detailed occupational and environmental histories were taken from subjects and their families, searching for past contact with asbestos.

RESULTS: The cases were diagnosed in a short period of time (two years), in a region of the country where many asbestos cement plants are located since the mid sixties. Skillful histological procedures were used. From these cases we found out that one had a twelve months period of exposure, 24 years before, in one of those plants. Another patient had an exposure for three years, as a bystander, in the same plant (also 24 years before) and a third patient was contaminated by asbestos brought home by his father in the 1950s (latency period of 30 years). All cases were histochemically studied and diagnosis confirmed by the presence of microvilli at electronmicroscopic examination.

CONCLUSIONS: These three cases seem to confirm the existence of the epidemiologic association with asbestos exposure in our country. Definition of diagnosis criteria, centralization of cases registry and the necessity of more attention to this kind of asbestos related disease are discussed and stressed, as many new cases like those described are thought to occur in the near future, as the latency period of the disease seems to match with that of industrial asbestos manipulation in Brazil.}, } @article {pmid9396218, year = {1997}, author = {Maltoni, C and Pinto, C}, title = {Mesotheliomas in some selected Italian population groups.}, journal = {La Medicina del lavoro}, volume = {88}, number = {4}, pages = {321-332}, pmid = {9396218}, issn = {0025-7818}, mesh = {Asbestos/adverse effects ; Carcinogens/adverse effects ; Female ; Glass ; Heart Neoplasms/*epidemiology/etiology ; Humans ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology/etiology ; Occupational Exposure/adverse effects/statistics & numerical data ; *Pericardium ; Peritoneal Neoplasms/*epidemiology/etiology ; Pleural Neoplasms/*epidemiology/etiology ; }, abstract = {The analysis of 335 cases of mesothelioma observed at the Ramazzini Foundation and the Bologna Institute of Oncology has shown: 1) a high percentage of correlation of these tumours with asbestos exposure; 2) a large number of population categories potentially exposed to asbestos fibres and therefore at risk of developing mesothelioma; and 3) the high risk of mesothelioma among people exposed in various circumstances to asbestos used in railroads and sugar refinery plants.}, } @article {pmid9396217, year = {1997}, author = {Giarelli, L and Grandi, G and Bianchi, C}, title = {Malignant mesothelioma of the pleura in the Trieste-Monfalcone area, with particular regard to shipyard workers.}, journal = {La Medicina del lavoro}, volume = {88}, number = {4}, pages = {316-320}, pmid = {9396217}, issn = {0025-7818}, mesh = {Asbestosis/complications/epidemiology ; Female ; Humans ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology/etiology/genetics ; Occupational Diseases/*epidemiology/etiology ; Pleural Neoplasms/*epidemiology/etiology/genetics ; *Ships ; Time Factors ; }, abstract = {A series of 421 malignant pleural mesotheliomas, diagnosed in the Trieste-Monfalcone area, northeastern Italy, were reviewed. A large majority of the patients had been employed in "naval" work (shipbuilding, maritime trades, and dock work). Latency periods (time intervals between first exposure to asbestos and death), showed wide variations from one occupational category to another. Such variations were attributable, but only partly, to differences in the intensity of the exposure to asbestos. Various family cases were identified, including people with and without blood relationships. The data, obtained in the studies on Trieste-Monfalcone mesothelioma, suggest that interactions between asbestos and other factors play a considerable role in the pathogenesis of asbestos-related mesothelioma.}, } @article {pmid9396216, year = {1997}, author = {Seniori Costantini, A and Chellini, E}, title = {The experience of the Mesothelioma Registry of Tuscany in assessing health hazard associated with asbestos exposure.}, journal = {La Medicina del lavoro}, volume = {88}, number = {4}, pages = {310-315}, pmid = {9396216}, issn = {0025-7818}, mesh = {Age Distribution ; Aged ; Asbestos/*adverse effects ; Carcinogens/*adverse effects ; Female ; Humans ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Exposure/*adverse effects/statistics & numerical data ; Pleural Neoplasms/*epidemiology/etiology ; Prevalence ; Registries/*statistics & numerical data ; Sex Distribution ; }, abstract = {All cases of pleural malignant mesothelioma occurring in Tuscany were collected, backdated to 1980 (to 1970 for the provinces of Florence and Prato; to 1975 for the provinces of Pisa and Siena), in order to evaluate the incidence of occupational exposure to asbestos. The aim was to enhance primary prevention in those workplaces still at risk nowadays. To achieve information on the possible occupational, domestic or environmental exposure, an interview was conducted using a semi-structured questionnaire. An exposure classification was produced to focus preventive intervention. This surveillance system needs to be developed to contribute to epidemiological research, especially on the effects of low level exposures, and to primary prevention.}, } @article {pmid9396215, year = {1997}, author = {Magnani, C and Ivaldi, C and Botta, M and Terracini, B}, title = {Pleural malignant mesothelioma and environmental asbestos exposure in Casale Monferrato, Piedmont. Preliminary analysis of a case-control study.}, journal = {La Medicina del lavoro}, volume = {88}, number = {4}, pages = {302-309}, pmid = {9396215}, issn = {0025-7818}, mesh = {Aged ; Asbestos/*adverse effects ; Carcinogens/*adverse effects ; Case-Control Studies ; Confidence Intervals ; Environmental Exposure/*adverse effects/statistics & numerical data ; Female ; Humans ; Italy/epidemiology ; Logistic Models ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Odds Ratio ; Pleural Neoplasms/*epidemiology/etiology ; }, abstract = {A case-control study on pleural malignant mesothelioma (MM) was conducted in Casale Monferrato, where the largest Italian asbestos cement (AC) factory had been operating from 1907 to 1985. In a previous study we observed a five to seven-fold increase in the incidence of MM among people living in that city and never employed in the factory mentioned. The present study includes cases of MM with histological diagnosis over the period 1.1.1987-30.6.1993 among residents in the Local Health Unit (LHU) of Casale Monferrato. Population controls were randomly extracted from the list of the residents in the LHU, matched to cases on sex, date of birth, vital status and date of death. Cases and controls (or their closest relative) were interviewed with a standardised questionnaire focusing on asbestos exposure in the (life-long) residential and occupational histories and in leisure time activities as well as on occupational asbestos exposure of relatives and cohabitants, smoking and chest or occupational diseases. The interview was blind in respect to case or control status. For the analyses the addresses were coded on map grids with a 500 m. mesh size. Statistical analyses were conducted with conditional logistic regression in order to keep the matching between cases and controls. Eighty-eight cases and 244 controls were interviewed (95.6% of cases and 80.1% of controls): 26 and 11 respectively reported an activity in the AC industry. Seven cases and 7 controls were also exposed because of parental occupation. The main analyses are based on the conditional regression model including both occupational and residential exposure. The different modes of exposure are included on an ordinal scale: each subject is classified according to their highest level. Domestic exposure is included as an independent factor. Odds Ratios (OR) are estimated with reference to subjects without either occupational or residential exposure. The OR is 39.3 among subjects reporting occupational exposure, 11.9 among those never engaged in the AC industry but living within 1000 m. of the factory. A statistically significant risk is also observed for persons at some time living in the other areas of Casale Monferrato.}, } @article {pmid9396213, year = {1997}, author = {Lemen, RA}, title = {Introduction: history of the use of asbestos.}, journal = {La Medicina del lavoro}, volume = {88}, number = {4}, pages = {288-292}, pmid = {9396213}, issn = {0025-7818}, mesh = {Animals ; Asbestos/adverse effects/*history ; Asbestosis/etiology/veterinary ; Carcinogens/adverse effects/*history ; History, 20th Century ; Humans ; Lung Neoplasms/etiology ; }, abstract = {Discussion of the major milestones in the history of the modern uses of asbestos and the first knowledge of the health effects associated with such usage. Highlights of the studies associating exposure to asbestos with non-malignant lung diseases, lung cancer, and mesothelioma are discussed.}, } @article {pmid9210725, year = {1997}, author = {Murai, Y and Kitagawa, M and Hiraoka, T}, title = {Fiber analysis in lungs of residents of a Japanese town with endemic pleural plaques.}, journal = {Archives of environmental health}, volume = {52}, number = {4}, pages = {263-269}, doi = {10.1080/00039899709602196}, pmid = {9210725}, issn = {0003-9896}, mesh = {Aged ; Asbestos/*analysis ; Chi-Square Distribution ; Female ; Humans ; Japan ; Lung/*chemistry ; Lung Neoplasms/pathology ; Male ; Microscopy, Electron ; Middle Aged ; Mineral Fibers/analysis/statistics & numerical data ; Particle Size ; Pleural Diseases/*pathology ; *Urban Population ; }, abstract = {The authors analyzed various types of fibers in lung-tissue samples, which were obtained from 50 cases (46 surgical resections and 4 autopsies) at Kumamoto-Minami Hospital in Matsubase, where the occurrence of pleural plaques is endemic. Lung cancer necessitated surgical resection in 44 cases. Eleven of the 50 cases were residents of Matsubase; 15 resided in the region around the town, where the frequency of pleural plaques was slightly higher; and 24 cases lived in a region with normal plaque frequency. The number of anthophyllite fibers in the lungs of town residents was significantly higher than in residents of the region with normal plaque frequency. In 6 cases, the authors found accompanying pleural plaques, and the anthophyllite fiber count in the lungs in these cases was significantly higher than in cases without plaques. In addition, the anthophyllite fiber counts in 2 cases with severe plaques were significantly higher in 4 cases with only mild plaques. These results suggested that anthophyllite fiber might be responsible for the increased prevalence of pleural plaques in Matsubase. Even though the anthophyllite fibers were quite long (mean length = 25.1 microm), the width of most anthophyllite fibers were thick (mean diameter = 0.84 microm). Therefore, the aspect ratio of anthophyllite (mean = 38.7) was lower than that of amosite (mean = 81.8), which, in a previous report, was found predominantly in cases of pleural mesothelioma. Perhaps these differences in fiber size are related to the strength of the carcinogenicity to the pleura.}, } @article {pmid9205997, year = {1997}, author = {Dodson, RF and O'Sullivan, M and Corn, CJ and McLarty, JW and Hammar, SP}, title = {Analysis of asbestos fiber burden in lung tissue from mesothelioma patients.}, journal = {Ultrastructural pathology}, volume = {21}, number = {4}, pages = {321-336}, doi = {10.3109/01913129709021930}, pmid = {9205997}, issn = {0191-3123}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*isolation & purification ; Asbestosis/etiology ; Body Burden ; Female ; Humans ; Lung Neoplasms/*etiology/mortality ; Male ; Mesothelioma/*etiology/mortality ; Middle Aged ; Occupational Diseases/etiology/mortality ; Survival Rate ; }, abstract = {Mesothelioma is a rare neoplasm that occurs most frequently in individuals with previous asbestos exposure. Differences for risk of development of asbestos-related mesothelioma and lung cancer have been attributed to the various types of asbestos, as well as to the dimension of the inhaled fibers. In the present study, 55 individuals with the pathological diagnosis of mesothelioma were evaluated as to ferruginous body and fiber content in lung tissue. The procedures used in the analysis included tissue digestion and analysis of the collected material for ferruginous bodies by light microscopy and for uncoated fibers by analytical transmission electron microscopy. Forty-six of the samples had ferruginous body concentrations of over 1000/per gram dry weight of lung tissue. The majority of the cores of these ferruginous bodies were amosite. Likewise, the most common uncoated asbestos fiber in the tissue was amosite. Only a small percentage of each type of asbestos would have been visible by light microscopy or even potentially by electron microscopy if the magnification was not sufficient to detect those with thin (< 0.2 micron) diameters. The consistent finding in most of the cases was a considerable presence of asbestos, often of mixed types.}, } @article {pmid9248100, year = {1997}, author = {Brochard, P}, title = {[Epidemiological approach to mesothelioma].}, journal = {La Revue du praticien}, volume = {47}, number = {12}, pages = {1326-1332}, pmid = {9248100}, issn = {0035-2640}, mesh = {Asbestos/administration & dosage/adverse effects ; Asbestos, Amphibole/adverse effects ; Asbestos, Serpentine/adverse effects ; *Environmental Exposure ; France/epidemiology ; Humans ; Incidence ; Male ; Mesothelioma/diagnosis/*epidemiology/etiology ; Middle Aged ; Mineral Fibers/adverse effects ; Pleural Neoplasms/diagnosis/*epidemiology/etiology ; }, abstract = {Mesothelioma, the primitive cancer of pleura, peritoneum or pericardium, is a tumor for which many etiologic studies have been conducted, because of close relations with environment. If asbestos remains the essential risk factor, many uncertainties persist on extent of phenomena in next decades. Furthermore, emergence of new etiologies, confirmed on human (erionite, ionizing radiations) or only suspected in experimentation (some biopersistent synthetic fibers, some virus as the SV40), ask new questions which are susceptible to modify our view of mesothelioma epidemiology.}, } @article {pmid9252860, year = {1997}, author = {Gentiloni, N and Febbraro, S and Barone, C and Lemmo, G and Neri, G and Zannoni, G and Capelli, A and Gasbarrini, G}, title = {Peritoneal mesothelioma in recurrent familial peritonitis.}, journal = {Journal of clinical gastroenterology}, volume = {24}, number = {4}, pages = {276-279}, doi = {10.1097/00004836-199706000-00023}, pmid = {9252860}, issn = {0192-0790}, mesh = {Adult ; Familial Mediterranean Fever/*complications/epidemiology/genetics ; Humans ; Male ; Mesothelioma/*complications/epidemiology ; Peritoneal Neoplasms/*complications/epidemiology ; Peritonitis/*complications/genetics ; }, abstract = {A 39-year-old man had a 2-year history of fatigue, weight loss, drug-resistant ascites, and decreased intestinal motility. During adolescence he began to suffer frequent episodes of acute benign peritonitis that spontaneously subsided at age 35. The fact that his younger brother was taking colchicine for the same symptoms led us to diagnose familial Mediterranean fever (FMF). The medical workup revealed uniform thickening of the intestinal wall with no signs of amyloidosis. Exploratory laparotomy revealed diffuse peritoneal mesothelioma that proved to be unresponsive to chemotherapy. There was no history of asbestos exposure. It is probable that the chronic peritoneal inflammation was responsible for the development of this tumor, although in almost all cases of FMF this phenomenon causes only limited peritoneal fibrosis or, less commonly, encapsulating peritonitis. A computerized search of the literature indicates that this is the second report of peritoneal mesothelioma associated with FMF.}, } @article {pmid9248440, year = {1997}, author = {Munson, M}, title = {Mesothelioma.}, journal = {Professional nurse (London, England)}, volume = {12}, number = {9}, pages = {651-653}, pmid = {9248440}, issn = {0266-8130}, mesh = {Asbestos/*adverse effects ; Humans ; Incidence ; *Mesothelioma/diagnosis/etiology/therapy ; *Peritoneal Neoplasms/diagnosis/etiology/therapy ; *Pleural Neoplasms/diagnosis/etiology/therapy ; }, } @article {pmid9245946, year = {1997}, author = {Howel, D and Arblaster, L and Swinburne, L and Schweiger, M and Renvoize, E and Hatton, P}, title = {Routes of asbestos exposure and the development of mesothelioma in an English region.}, journal = {Occupational and environmental medicine}, volume = {54}, number = {6}, pages = {403-409}, pmid = {9245946}, issn = {1351-0711}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Case-Control Studies ; England/epidemiology ; Environmental Exposure/*adverse effects ; Female ; Humans ; Logistic Models ; Male ; Mesothelioma/*chemically induced/epidemiology ; Middle Aged ; Odds Ratio ; }, abstract = {OBJECTIVES: To investigate the contribution of exposure to asbestos through different routes in the development of mesothelioma.

METHODS: Case-control study. 185 confirmed cases of mesothelioma and 160 controls were identified, when death had occurred between 1979 and 1991 in four health districts in Yorkshire. The surviving relatives were interviewed to ascertain lifetime exposure to asbestos. Adjusted odds ratios (ORs) of exposure to asbestos (through occupational, paraoccupational, and residential routes) were calculated for cases and were compared with controls.

RESULTS: Likely or possible occupational exposure to asbestos was more common in cases than in controls (OR 5.6, 95% confidence interval (95% CI) 3.1 to 10.1). After excluding those with likely or possible occupational exposure, likely or possible paraoccupational exposure was more common in cases than controls (OR 5.8, 95% CI 1.8 to 19.2). Only six cases of mesothelioma were identified as being solely exposed to asbestos through their residence, compared with nine controls. The OR for residential exposure to asbestos varied between 1.5 and 6.6, depending on which potential industrial sources were included, but the 95% CIs were so wide that slightly reduced or greatly increased odds comparing cases with controls could not be excluded.

CONCLUSION: Study results support previous evidence that occupational and paraoccupational exposure to asbestos is associated with developing mesothelioma. Despite a rigorous search, purely residential exposure seemed to account for only 3% of identified cases. No firm conclusion can be drawn about the risks from residential exposure alone, as many of the study subjects could also have been occupationally or paraoccupationally exposed to asbestos.}, } @article {pmid9227715, year = {1997}, author = {Yates, DH and Corrin, B and Stidolph, PN and Browne, K}, title = {Malignant mesothelioma in south east England: clinicopathological experience of 272 cases.}, journal = {Thorax}, volume = {52}, number = {6}, pages = {507-512}, pmid = {9227715}, issn = {0040-6376}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; England/epidemiology ; *Environmental Exposure ; Female ; Humans ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Diseases/*epidemiology/etiology ; Pleural Neoplasms/*epidemiology/etiology ; }, abstract = {BACKGROUND: Malignant mesothelioma is a rare pleural tumour associated with asbestos exposure. The proportion of malignant mesothelioma unrelated to asbestos exposure, and any differentiating features between exposed and unexposed cases, are not well described. This study describes occupational, clinical, and pathological features in a large cohort of cases of malignant mesothelioma from south east England.

METHODS: All 272 cases from this region were studied, either in life or after death when necropsy examination suggested malignant mesothelioma. Detailed information was gathered regarding the occupational history, clinical course, and mode of death. Necropsies were performed in 98% of cases. Lung tissue was examined histologically to confirm the diagnosis, subtype of tumour, presence or absence of asbestosis and asbestos bodies.

RESULTS: Exposure to asbestos was documented in 87% of cases, while in the remainder, no asbestos exposure was found nor were asbestos bodies seen; 94.5% were pleural, 5.1% peritoneal, and 0.4% pericardial. Right sided tumours were more common than left sided tumours (ratio 1.6:1). Patients usually presented with breathlessness and chest pain, but 33% presented with pleural effusion in the absence of chest pain. The mean (SD) time from first exposure to asbestos to symptoms was 40 (12) years with a median (interquartile range (IQR) survival of 14 (12.5) months. The median (IQR) survival time in sarcomatous, epithelial, and mixed cell type malignant mesothelioma was 9.4 (10) months, 12.5 (18) months, and 11 (14) months, respectively, and was significantly greater in cases detected by chance. Clinical features were similar in asbestos related and non-asbestos related malignant mesothelioma.

CONCLUSIONS: In south east England most cases of malignant mesothelioma are associated with asbestos exposure. Clinical features do not differentiate between asbestos related and non-asbestos related disease.}, } @article {pmid9227712, year = {1997}, author = {Hubbard, R}, title = {The aetiology of mesothelioma: are risk factors other than asbestos exposure important?.}, journal = {Thorax}, volume = {52}, number = {6}, pages = {496-497}, doi = {10.1136/thx.52.6.496}, pmid = {9227712}, issn = {0040-6376}, mesh = {Asbestos/*adverse effects ; Child ; Environmental Exposure/*adverse effects ; Humans ; Lung Neoplasms/*etiology ; Male ; Mesothelioma/*etiology ; Middle Aged ; Mineral Fibers/*adverse effects ; Occupational Diseases/*etiology ; Risk Factors ; }, } @article {pmid9131226, year = {1997}, author = {Kang, SK and Burnett, CA and Freund, E and Walker, J and Lalich, N and Sestito, J}, title = {Gastrointestinal cancer mortality of workers in occupations with high asbestos exposures.}, journal = {American journal of industrial medicine}, volume = {31}, number = {6}, pages = {713-718}, doi = {10.1002/(sici)1097-0274(199706)31:6<713::aid-ajim7>3.0.co;2-r}, pmid = {9131226}, issn = {0271-3586}, mesh = {*Asbestos/adverse effects ; Colorectal Neoplasms/mortality ; Esophageal Neoplasms/mortality ; Gastrointestinal Neoplasms/*mortality ; Humans ; Male ; Mesothelioma/mortality ; *Occupational Exposure ; Risk Factors ; Stomach Neoplasms/mortality ; United States/epidemiology ; }, abstract = {Asbestos, which is a well-known risk factor for lung cancer and malignant mesothelioma, has also been suggested as a gastrointestinal (GI) carcinogen. This study was conducted to assess the relationship between high asbestos exposure occupations and the occurrence of G1 cancer. Death certificate data were analyzed from 4,943,566 decedents with information on occupation and industry from 28 states from 1979 through 1990. Elevated proportionate mortality ratios (PMRs) for mesothelioma were used to identify occupations potentially having many workers exposed to asbestos. All PMRs were age-adjusted and sex- and race-specific. The PMRs for GI cancers in white males were then calculated for these occupations after excluding mesothelioma, lung cancer, and non-malignant respiratory disease from all deaths. We identified 15,524 cases of GI cancer in the 12 occupations with elevated PMRs for mesothelioma. When these occupations were combined, the PMRs for esophageal, gastric, and colorectal cancer were significantly elevated at 108 (95% confidence interval = 107-110), 110 (106-113), and 109 (107-110), respectively. Esophageal cancer was elevated in sheet metal workers and mechanical workers. Gastric cancer was elevated in supervisors in production and managers. Colorectal cancer was elevated in mechanical and electrical and electronic engineers. However, high exposure occupations like insulation, construction painter supervisors, plumbers, furnace operators, and construction electricians showed no elevations of GI cancers. In conclusion, this death certificate study supports an association between asbestos exposure and some GI cancer, however the magnitude of this effect is very small.}, } @article {pmid9131224, year = {1997}, author = {De Vuyst, P and Dumortier, P and Gevenois, PA}, title = {Analysis of asbestos bodies in BAL from subjects with particular exposures.}, journal = {American journal of industrial medicine}, volume = {31}, number = {6}, pages = {699-704}, doi = {10.1002/(sici)1097-0274(199706)31:6<699::aid-ajim5>3.0.co;2-m}, pmid = {9131224}, issn = {0271-3586}, mesh = {Aged ; Asbestos/*analysis ; Bronchoalveolar Lavage Fluid/*chemistry ; Female ; Humans ; Male ; Middle Aged ; Mineral Fibers/analysis ; *Occupational Exposure ; Pleural Diseases/*etiology ; Pulmonary Alveoli ; }, abstract = {Four patients with asbestos-related diseases and with unusual exposures underwent bronchoalveolar lavage (BAL) for mineralogical analysis. Asbestos bodies (AB) were counted by light microscopy and analyzed by transmission electron microscopy and X-ray energy spectrometry. AB's were found in all cases, after a mean delay from the end of exposure of 27.7 years. Analysis of the core fibers indicated the type of alveolar asbestos burden and was compared with the previous exposures: Pleural plaques due to household exposure to amosite and crocidolite. Pleural plaques due to occult occupational exposure to crocidolite in a coal miner. Asbestosis due to environmental exposure to tremolite in Turkey. Asbestosis, pleural plaques, and peritoneal mesothelioma due to a short, intense exposure to crocidolite. AB counting in BAL and identification of the central fibers by analytical electron microscopy is a useful, non-invasive and reliable method to evaluate the alveolar retention of bio-persistent fibers and to relate them to specific exposures.}, } @article {pmid9131223, year = {1997}, author = {Oksa, P and Pukkala, E and Karjalainen, A and Ojajärvi, A and Huuskonen, MS}, title = {Cancer incidence and mortality among Finnish asbestos sprayers and in asbestosis and silicosis patients.}, journal = {American journal of industrial medicine}, volume = {31}, number = {6}, pages = {693-698}, doi = {10.1002/(sici)1097-0274(199706)31:6<693::aid-ajim4>3.0.co;2-s}, pmid = {9131223}, issn = {0271-3586}, mesh = {Adult ; Aged ; Asbestosis/*mortality ; Female ; Finland/epidemiology ; Follow-Up Studies ; Humans ; Lung Neoplasms/epidemiology/mortality ; Male ; Mesothelioma/epidemiology/mortality ; Middle Aged ; Neoplasms/*epidemiology/mortality ; Respiratory Tract Diseases/mortality ; Silicosis/*mortality ; Vascular Diseases/mortality ; }, abstract = {Cohorts of Finnish asbestos sprayers and of asbestosis and silicosis patients were followed for cancer with the aid of the Finnish Cancer Registry in the period 1967-1994. Compared with the cancer incidence of the total Finnish population, asbestos sprayers had an increased risk for total cancer (standardized incidence ratio [SIR] 6.7, 95% confidence interval [95% CI] 4.2-10); lung cancer (SIR 17.95% CI 8.2-31); and mesothelioma (SIR 263, 95% CI 85-614). The SIR of the asbestosis patients was 3.7 (95% CI 2.8-5.0) for all sites, 10 (95% CI 6.9-14) for lung cancer, and 65 (95% CI 13-188) for mesothelioma. The silicosis patients also had significantly high SIR values for all sites (1.5, 95% CI 1.0-2.1) and lung cancer (2.7, 95% CI 1.5-4.5). The values for the SIR and the standardized mortality ratio for all sites and lung cancer were very similar, and therefore it seems that both are reliable indicators of the occurrence of occupational cancer. It was concluded that pneumoconioses patients and asbestos-exposed workers have a markedly elevated risk for cancer. Asbestos-induced occupational cancers are not only diseases of the elderly, since the relative risk is high also for middle-aged people.}, } @article {pmid9380136, year = {1997}, author = {Burdorf, A and Barendregt, JJ and Swuste, PH and Heederik, DJ}, title = {[Future increase of the incidence of mesothelioma due to occupational exposure to asbestos in the past].}, journal = {Nederlands tijdschrift voor geneeskunde}, volume = {141}, number = {22}, pages = {1093-1098}, pmid = {9380136}, issn = {0028-2162}, mesh = {Asbestos/*adverse effects ; Cohort Studies ; Humans ; Incidence ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; Netherlands/epidemiology ; Occupational Diseases/mortality ; Occupational Exposure/*adverse effects ; }, abstract = {OBJECTIVE: To estimate the future course of mesothelioma mortality as a result of occupational exposure to asbestos in the past.

DESIGN: Cohort age model.

SETTING: Department of Public Health, Erasmus University Rotterdam, the Netherlands.

METHODS: A cohort age model was developed, based upon age-specific rates of pleural mesothelioma mortality during 1969-1994. This model was linked to the future trend in mortality among Dutch men as projected by the Central Bureau for Statistics in order to predict the future course of mesothelioma mortality in the period 1995-2030.

RESULTS: In the next 35 years about 20,000 cases of pleural mesothelioma among men are expected. The projection results in a peak of annual male mesothelioma deaths of approximately 700 in about the year 2018. After 2020 the annual mortality will rapidly decline to about 450 cases in 2030. It is expected that this rapid decline will continue after 2030. In the 1943-1947 birth cohort pleural mesothelioma may account for 0.87% of all deaths. Exposure to asbestos at work largely explains this particular mortality pattern.

CONCLUSION: Exposure to asbestos at work has created an important public health problem among Dutch men.}, } @article {pmid9380133, year = {1997}, author = {Leclercq, RM and Jongmans-Liedekerken, AW}, title = {[Malignant pleural mesothelioma in general practice; complex pain problems].}, journal = {Nederlands tijdschrift voor geneeskunde}, volume = {141}, number = {22}, pages = {1081-1085}, pmid = {9380133}, issn = {0028-2162}, mesh = {Aged ; Analgesics, Opioid/administration & dosage/*therapeutic use ; Asbestos/adverse effects ; Humans ; Lung Neoplasms/*complications/etiology ; Male ; Mesothelioma/*complications/etiology ; Middle Aged ; Morphine/administration & dosage/*therapeutic use ; Pain, Intractable/etiology/*prevention & control ; }, abstract = {In three patients, men aged 67, 57 and 69 years, malignant pleural mesothelioma was diagnosed. All three had worked as coal miners and were presented with thoracic pain. They were among seven cases of malignant pleural mesothelioma diagnosed in a period of five years in one suburban general practice (adherence: 5600 patients) in the former mining area in the province of Limburg. The terminal phase of the disease was characterized by intractable pain. High doses of opioids and adjuvants were necessary to achieve acceptable pain relief. It is suggested that step one of the 'analgesic ladder for cancer pain management' of the WHO (non-opioids) should be followed soon by step three (strong opioids). Because the incidence of pleural mesothelioma is not yet decreasing, it is important to know that pain management remains a serious problem.}, } @article {pmid9149015, year = {1997}, author = {Pennucci, MC and Ardizzoni, A and Pronzato, P and Fioretti, M and Lanfranco, C and Verna, A and Giorgi, G and Vigani, A and Frola, C and Rosso, R}, title = {Combined cisplatin, doxorubicin, and mitomycin for the treatment of advanced pleural mesothelioma: a phase II FONICAP trial. Italian Lung Cancer Task Force.}, journal = {Cancer}, volume = {79}, number = {10}, pages = {1897-1902}, doi = {10.1002/(sici)1097-0142(19970515)79:10<1897::aid-cncr9>3.0.co;2-d}, pmid = {9149015}, issn = {0008-543X}, mesh = {Adult ; Aged ; Antibiotics, Antineoplastic/administration & dosage/adverse effects ; Antineoplastic Agents/administration & dosage/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use ; Bone Marrow/drug effects ; Chest Pain/pathology ; Cisplatin/administration & dosage/adverse effects ; Disease Progression ; Doxorubicin/administration & dosage/adverse effects ; Dyspnea/pathology ; Feasibility Studies ; Female ; Humans ; Infusions, Intravenous ; Male ; Mesothelioma/*drug therapy ; Middle Aged ; Mitomycins/administration & dosage/adverse effects ; Neoplasm Staging ; Pleural Effusion, Malignant/pathology ; Pleural Neoplasms/*drug therapy ; Remission Induction ; }, abstract = {BACKGROUND: In a previous FONICAP trial, the combination of doxorubicin (D) and cisplatin (P) yielded an objective response rate of 25% and a subjective response rate of 50% in patients with mesothelioma. In human mesothelioma cell lines, mitomycin (M) showed a synergic activity with P and in a recent randomized study, the combination of M and P showed slightly superior activity when compared with the PD regimen.

METHODS: The authors tested the activity and toxicity of a combination chemotherapy regimen including P, 60 mg/m2, D, 60 mg/m2, and M, 10 mg/m2, all by intravenous infusion on Day 1 every 28 days in a Phase II study.

RESULTS: Twenty-four chemotherapy-naive mesothelioma patients were enrolled in the study. Patient characteristics were the following: the median age was 58 years; the median performance status was 1; there were 6 Stage I patients, 15 Stage II patients, 2 Stage III patients, and 1 Stage IV patient; and 10 patients had previous asbestos exposure. All patients had pretreatment symptoms: 13 had chest pain, 9 had pleural effusion, and 7 had dyspnea. A total of 78 cycles of chemotherapy were administered. The only significant side effect was myelosuppression, with only 9.5% of patients having Grade 4 toxicity. Among 23 patients evaluable for response, 5 achieved a partial response (20.8%; 95% confidence interval, 7.1-42.1%), 9 had stable disease, and 9 had progressive disease (including 1 early death). One patient was not evaluable because of treatment refusal. A clinical improvement was observed in 7 of 24 patients (29%).

CONCLUSIONS: The combination of PDM in patients with pleural mesothelioma is feasible and moderately active. However, the observed level of activity is similar to that obtained with other two-drug regimens.}, } @article {pmid9142077, year = {1997}, author = {Wagner, GR}, title = {Asbestosis and silicosis.}, journal = {Lancet (London, England)}, volume = {349}, number = {9061}, pages = {1311-1315}, doi = {10.1016/S0140-6736(96)07336-9}, pmid = {9142077}, issn = {0140-6736}, mesh = {*Asbestosis/diagnostic imaging/etiology/mortality ; Gastrointestinal Neoplasms/etiology ; Humans ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Occupational Exposure/adverse effects ; Radiography ; Risk Factors ; *Silicosis/diagnostic imaging/etiology/mortality ; }, abstract = {Interstitial fibrosis resulting from workplace exposure to asbestos and crystalline silica persists throughout the world despite knowledge of the causes and effective means for prevention. Asbestosis and silicosis occurrence is predictable among people overexposed to dusts in various industries and occupations such as mining, construction, manufacturing, and building maintenance. Asbestosis and silicosis are incurable and may be progressive even after dust exposure has ceased, therefore early recognition and supportive interventions are important. Although current disease is a result of past exposures, effective control of current workplace exposures is the only way to prevent continued occurrence of these potentially debilitating diseases. Physicians can contribute to this effort through accurate diagnosis and disease reporting.}, } @article {pmid9139887, year = {1997}, author = {Leong, CC and Marley, JV and Loh, S and Milech, N and Robinson, BW and Garlepp, MJ}, title = {Transfection of the gene for B7-1 but not B7-2 can induce immunity to murine malignant mesothelioma.}, journal = {International journal of cancer}, volume = {71}, number = {3}, pages = {476-482}, doi = {10.1002/(sici)1097-0215(19970502)71:3<476::aid-ijc28>3.0.co;2-c}, pmid = {9139887}, issn = {0020-7136}, mesh = {Animals ; Antigens, CD/*biosynthesis/genetics ; Asbestos ; B7-1 Antigen/*biosynthesis/genetics ; B7-2 Antigen ; Cell Division ; Cell Line ; *Cytotoxicity, Immunologic ; Humans ; Lymphocyte Depletion ; Membrane Glycoproteins/*biosynthesis/genetics ; Mesothelioma/etiology/*immunology/*therapy ; Mice ; Recombinant Proteins/biosynthesis ; Spleen/immunology ; T-Lymphocytes/immunology ; T-Lymphocytes, Cytotoxic/*immunology ; Transfection/immunology/*methods ; Tumor Cells, Cultured ; }, abstract = {Transfection of the genes encoding the co-stimulatory molecules B7-1 and B7-2 has enhanced the development of immunity to a variety of experimental tumors, although most of these were inherently immunogenic. We have determined the effect of expression of these genes on the induction of immunity to 2 non-immunogenic murine malignant mesothelioma (MM) cell lines (AC29 and AB1). We had previously shown that B7-1 transfection into AC29 delayed but did not prevent tumor development by certain of the transfectant clones. Here we demonstrate that over-expression of B7-1 can inhibit tumor development by certain AB1-B7-1 clones, that inhibition of transfectant growth is dependent on CD4+ and CD8+ T cells and that mice that reject some of these transfectant clones are capable of rejecting subsequent inocula of the parental cell line, AB1. The transfectant clones can generate tumor-specific cytotoxic T cells. By contrast, expression of B7-2 in several clones derived from either AB1 or AC29 had no significant effect on the development of tumors in vivo. Our data are consistent with data from other systems that show differences in the effect of modification by B7-1 or B7-2 on the modulation of anti-tumor immune responses. They demonstrate that such modifications can induce protective immunity against an MM cell line but confirm the intra- and inter-tumoral heterogeneity in the effect of genetic modification on the induction of immunity. Our observations are relevant to human MM because these cell lines have been derived from asbestos-induced tumors and share many properties with human cell lines of the same histological type.}, } @article {pmid9498906, year = {1997}, author = {Steenland, K and Stayner, L}, title = {Silica, asbestos, man-made mineral fibers, and cancer.}, journal = {Cancer causes & control : CCC}, volume = {8}, number = {3}, pages = {491-503}, doi = {10.1023/a:1018469607938}, pmid = {9498906}, issn = {0957-5243}, mesh = {Animals ; Asbestos/*adverse effects/chemistry ; Asbestos, Serpentine/adverse effects ; Carcinogens/*adverse effects ; Ceramics/adverse effects ; Confidence Intervals ; Confounding Factors, Epidemiologic ; Construction Materials ; Crystallization ; Disease Models, Animal ; Glass ; Humans ; Lung Neoplasms/epidemiology/*etiology ; Mesothelioma/epidemiology/etiology ; Meta-Analysis as Topic ; Mineral Fibers/*adverse effects ; Mining ; Occupational Diseases/epidemiology/*etiology ; Occupational Exposure ; Oxygen/analysis ; Probability ; Risk Factors ; Silicon/analysis ; Silicon Dioxide/*adverse effects/analysis/chemistry ; Silicosis/epidemiology/etiology ; United States/epidemiology ; }, abstract = {Approximately three million workers in the United States are estimated to be exposed to silica, man-made mineral fibers, and asbestos. The lung is the primary target organ of concern. Each of these substances is composed predominantly of silicon and oxygen; asbestos and silica are crystalline, and asbestos and man-made mineral fibers are fibers. Man-made mineral fibers and asbestos are used as insulating agents, with the former having generally replaced the latter in recent years. Silica is used in foundries, pottery, and brick making, and is encountered by miners. A meta-analysis of 16 of the largest studies with well-documented silica exposure and low probability of confounding by other occupational exposures, indicates a relative risk (RR) of 1.3 (95 percent confidence interval [CI] = 1.2-1.4). Lung cancer risks are highest and most consistent for silicotics, who have received the highest doses (RR = 2.3, CI = 2.2-2.4, across 19 studies). The data for mineral fibers continue to support the International Association for Research on Cancer's 1988 judgment that mineral fibers are a possible human carcinogen (Group 2B). Recent epidemiologic studies provide little evidence for lung carcinogenicity for either glass wool or rock/slag wool. Ceramic fibers, a much less common exposure than glass wool and rock/slag wool, are of concern because of positive animal studies, but there are insufficient human data. Regarding asbestos, its carcinogenicity for the lung and mesothelium is well established. With regard to the controversy over chrysotile and mesothelioma, the data suggest chrysotile does cause mesothelioma, although it may be less potent than amphibole asbestos.}, } @article {pmid9260356, year = {1997}, author = {Teschke, K and Morgan, MS and Checkoway, H and Franklin, G and Spinelli, JJ and van Belle, G and Weiss, NS}, title = {Mesothelioma surveillance to locate sources of exposure to asbestos.}, journal = {Canadian journal of public health = Revue canadienne de sante publique}, volume = {88}, number = {3}, pages = {163-168}, pmid = {9260356}, issn = {0008-4263}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; British Columbia/epidemiology ; Case-Control Studies ; Confidence Intervals ; Female ; Humans ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Diseases/*epidemiology/etiology ; Occupational Exposure ; Odds Ratio ; Pleural Neoplasms/*epidemiology/etiology ; Population Surveillance ; Surveys and Questionnaires ; }, abstract = {To determine whether there were previously unrecognized sources of asbestos exposure in British Columbia, incident mesothelioma cases (n = 51) and population-based controls (n = 154) were interviewed about their occupational histories and asbestos exposures. The following occupations were at elevated risk: sheet metal workers (OR = 9.6, 95% CI: 1.5-106), plumbers and pipefitters (OR = 8.3, 95% CI: 1.5-86), shipbuilding workers (OR = 5.0, 95% CI: 1.2-23), painters (OR = 4.5, 95% CI: 1.0-24), welders (OR = 3.9, 95% CI: 0.8-22), gardeners (OR = 3.9, 95% CI: 0.8-22), bricklayers (OR = 3.5, 95% CI: 0.9-14), miners (OR = 3.4, 95% CI: 0.9-13), machinists (OR = 3.2, 95% CI: 1.0-11), construction foremen (OR = 3.1, 95% CI: 0.9-11), and electricians (OR = 3.0, 95% CI: 0.8-12). In a reanalysis excluding subjects who worked in occupations or processes considered strongly a priori at risk, three groups remained of interest: non-asbestos miners (OR = 9.6, 95% CI: 1.8-53), bricklayers (OR = 5.4, 95% CI: 1.0-28), and construction labourers (OR = 2.8, 95% CI: 0.7-10.6).}, } @article {pmid9197186, year = {1997}, author = {Jubelirer, SJ and Garcelon, J}, title = {Diffuse malignant pleural mesotheslioma at CAMC: a retrospective study of 50 patients.}, journal = {The West Virginia medical journal}, volume = {93}, number = {3}, pages = {120-125}, pmid = {9197186}, issn = {0043-3284}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Mesothelioma/diagnosis/mortality/*physiopathology ; Middle Aged ; Pleural Neoplasms/diagnosis/mortality/*physiopathology ; Prognosis ; Retrospective Studies ; Smoking ; Survival Analysis ; West Virginia ; }, abstract = {The cases of 50 patients who were treated for pleural diffuse malignant mesothelioma at Charleston Area Medical Center from 1966-1992 were reviewed retrospectively. Diagnosis was most often made by thoracoscopy or exploratory thoracotomy; pleural cytology was rarely contributory. The delay in diagnosis was often long (median time, 2.5 months; range 1-12 months). The median survival was only 6 months. Six clinical variables were analyzed for prognostic significance. Multivariate analysis showed that stage of disease, age, histology, and smoking history were the most important prognostic factors. Previous asbestos exposure was found in 74% of the patients. There was no cure of mesothelioma, and we did not find any significant differences in survival among groups of patients subjected to the different therapeutic measures. If new active therapies are identified, it would be useful to compare them to a best supportive care arm in order to demonstrate the value of any new therapeutic approach.}, } @article {pmid9181361, year = {1997}, author = {Attanoos, RL and Gibbs, AR}, title = {Pathology of malignant mesothelioma.}, journal = {Histopathology}, volume = {30}, number = {5}, pages = {403-418}, doi = {10.1046/j.1365-2559.1997.5460776.x}, pmid = {9181361}, issn = {0309-0167}, mesh = {Asbestos/adverse effects ; Diagnosis, Differential ; Heart Neoplasms/etiology/pathology ; Histocytochemistry ; Humans ; Male ; Mesothelioma/*etiology/*pathology ; Pericardium/pathology ; Peritoneal Neoplasms/*etiology/*pathology ; Pleural Neoplasms/*etiology/*pathology ; Testicular Neoplasms/etiology/pathology ; }, abstract = {The diagnosis of malignant mesothelioma can pose several problems to the surgical pathologist. First, the morphological appearances of the tumour are known to be diverse with mimicry of a range of both reactive and neoplastic conditions. Second, due to the relative inaccessibility of the serosa, biopsy material is often scanty and fragmentary, producing a plethora of interpretive ambiguities. Third, adjunct techniques such as mucin histochemistry and immunohistochemistry, whilst useful in excluding malignant mesothelioma have little role in confirming the diagnosis. The accurate diagnosis of diffuse malignant mesothelioma is important for two reasons: (1) In relation to prognosis as it has an almost invariable fatal outcome, which contrasts with the other mesothelial neoplasms such as the benign adenomatoid tumour and the borderline malignant tumours, namely the well-differentiated papillary mesothelioma and multicystic mesothelioma; (2) In relation to occupational-related compensation claims following asbestos exposure. This review summarizes the aetiology of asbestos-induced neoplasia, possible mechanisms of tumour development and highlights potential diagnostic pitfalls.}, } @article {pmid9156307, year = {1997}, author = {Hill, JK and Heitmiller, RF and Askin, FB and Kuhlman, JE}, title = {Localized benign pleural mesothelioma arising in a radiation field.}, journal = {Clinical imaging}, volume = {21}, number = {3}, pages = {189-194}, doi = {10.1016/s0899-7071(96)00024-1}, pmid = {9156307}, issn = {0899-7071}, mesh = {Aged ; Biopsy, Needle ; Breast Neoplasms/radiotherapy ; Female ; Humans ; Mesothelioma/diagnosis/*etiology/surgery ; Neoplasms, Radiation-Induced/diagnosis/*etiology/surgery ; Pleural Neoplasms/diagnosis/*etiology/surgery ; Radiotherapy, Adjuvant/adverse effects ; Tomography, X-Ray Computed ; }, abstract = {Localized benign pleural mesothelioma is a rare neoplasm representing less than 5% of all pleural tumors. Unlike the malignant diffuse pleural mesothelioma, there is no evidence of a relationship to asbestos exposure. Essentially, the cause of localized benign pleural mesotheliomas remains obscure. We propose that one mechanism of the development of this tumor is prior ionizing radiation to the tumor field. Ionizing radiation is a well-known human oncogen and leads to an increased incidence of benign tumors as well. A 65-year-old woman had a localized benign pleural mesothelioma of her left upper chest 22 years following adjuvant radiation therapy to the left breast and axillary region for a breast carcinoma.}, } @article {pmid9115020, year = {1997}, author = {Boffetta, P and Saracci, R and Andersen, A and Bertazzi, PA and Chang-Claude, J and Cherrie, J and Ferro, G and Frentzel-Beyme, R and Hansen, J and Olsen, J and Plato, N and Teppo, L and Westerholm, P and Winter, PD and Zocchetti, C}, title = {Cancer mortality among man-made vitreous fiber production workers.}, journal = {Epidemiology (Cambridge, Mass.)}, volume = {8}, number = {3}, pages = {259-268}, doi = {10.1097/00001648-199705000-00006}, pmid = {9115020}, issn = {1044-3983}, mesh = {Aged ; Aged, 80 and over ; Cohort Studies ; Confidence Intervals ; Europe/epidemiology ; Female ; Humans ; Lung Neoplasms/etiology/*mortality ; Male ; Middle Aged ; Mineral Fibers/*adverse effects ; Neoplasms/etiology/*mortality ; Occupational Diseases/etiology/*mortality ; Risk ; Risk Factors ; Time Factors ; }, abstract = {We have updated the follow-up of cancer mortality for a cohort study of man-made vitreous fiber production workers from Denmark, Finland, Norway, Sweden, United Kingdom, Germany, and Italy, from 1982 to 1990. In the mortality analysis, 22,002 production workers contributed 489,551 person-years, during which there were 4,521 deaths. Workers with less than 1 year of employment had an increased mortality [standardized mortality ratio (SMR) = 1.45; 95% confidence interval (CI) = 1.37-1.53]. Workers with 1 year or more of employment, contributing 65% of person-years, had an SMR of 1.05 (95% CI = 1.02-1.09). The SMR for lung cancer was 1.34 (95% CI = 1.08-1.63, 97 deaths) among rock/slag wool workers and 1.27 (95% CI = 1.07-1.50, 140 deaths) among glass wool workers. In the latter group, no increase was present when local mortality rates were used. Among rock/slag wool workers, the risk of lung cancer increased with time-since-first-employment and duration of employment. The trend in lung cancer mortality according to technologic phase at first employment was less marked than in the previous follow-up. We obtained similar results from a Poisson regression analysis limited to rock/slag wool workers. Five deaths from pleural mesothelioma were reported, which may not represent an excess. There was no apparent excess for other categories of neoplasm. Tobacco smoking and other factors linked to social class, as well as exposures in other industries, appear unlikely to explain the whole increase in lung cancer mortality among rock/slag wool workers. Limited data on other agents do not indicate an important role of asbestos, slag, or bitumen. These results are not sufficient to conclude that the increased lung cancer risk is the result of exposure to rock/slag wool; however, insofar as respirable fibers were an important component of the ambient pollution of the working environment, they may have contributed to the increased risk.}, } @article {pmid9173636, year = {1997}, author = {Molsted, K}, title = {[Forensic autopsies performed because of suspected occupational disease during the period 1987-1991--counties of Funen and Southern Jutland. Guidelines for physicians' notifications and a review of autopsy practice during 5 years].}, journal = {Ugeskrift for laeger}, volume = {159}, number = {18}, pages = {2711-2715}, pmid = {9173636}, issn = {0041-5782}, mesh = {Adult ; *Autopsy/statistics & numerical data ; Denmark ; Disease Notification ; Female ; Forensic Medicine/*legislation & jurisprudence ; Humans ; Lung Diseases/chemically induced/*pathology ; Male ; Middle Aged ; Occupational Diseases/chemically induced/*pathology ; Practice Patterns, Physicians' ; Registries ; Retrospective Studies ; }, abstract = {One hundred and thirty-six forensic autopsies were conducted at the Institute of Forensic Medicine, University of Odense, Denmark (covering the counties of Funen and Southern Jutland) between 1987 and 1991 suspecting occupational disease as the cause of death. The autopsy were requested by the National Board of Industrial Injuries (NBII). The most frequent exposures were asbestos, solvents, sand, dust and welding fumes. Death was caused by lung disease in 92/136 of the cases, of which 48 were lung cancers and ten mesotheliomas. Totally, cancer diseases were found to be the cause of death in 70/136. Comparing data from the official death register and from NBII on mesothelioma it is concluded that only a minor part of the deaths caused by occupational disease are reported. Only a fraction of the diseases listed in the official Danish inventory for occupational diseases were represented among these deaths. To ensure the relatives their rightful compensation and improve the statistical data used for prevention, it is important that doctors report all deaths which may have been caused by occupational diseases.}, } @article {pmid9507577, year = {1997}, author = {McLean, AN and Patel, KR}, title = {Clinical features and epidemiology of malignant pleural mesothelioma in west Glasgow 1987-1992.}, journal = {Scottish medical journal}, volume = {42}, number = {2}, pages = {37-39}, doi = {10.1177/003693309704200203}, pmid = {9507577}, issn = {0036-9330}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Incidence ; Male ; Mesothelioma/diagnosis/*epidemiology/mortality ; Middle Aged ; Pleural Neoplasms/diagnosis/*epidemiology/mortality ; Scotland/epidemiology ; Survival Rate ; }, abstract = {Malignant pleural mesothelioma is almost exclusively caused by exposure to asbestos dust. Recent epidemiological studies have suggested that the national incidence of disease may continue to rise until 2020 and that asbestos exposure in the building trade may be replacing shipyard related exposure as the main source of disease. The objective of the study was to determine if the incidence of malignant pleural mesothelioma was rising in the west of Glasgow from 1987-1992 and whether there had been a change in clinical features compared to previous studies from the same population. Case notes identified from coded returns and the local cancer registry were retrospectively examined: 144 cases were identified. This is an increase in incidence of over 50% compared to the previous study but the yearly incidence did not rise over the period studied. The clinical features and survival times have not changed since previous studies: median survival remains 30 weeks. Only three patients were given definitive treatment reflecting the lack of effective therapy. We suggest that the incidence of mesothelioma in the population studied may already have peaked resulting from the decline in the local shipyard industry over 20 years ago. Non-shipyard sources of asbestos exposure may be less important in this area.}, } @article {pmid9237066, year = {1997}, author = {Bianchi, C and Giarelli, L and Grandi, G and Brollo, A and Ramani, L and Zuch, C}, title = {Latency periods in asbestos-related mesothelioma of the pleura.}, journal = {European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP)}, volume = {6}, number = {2}, pages = {162-166}, pmid = {9237066}, issn = {0959-8278}, mesh = {Adult ; Age of Onset ; Aged ; Aged, 80 and over ; Analysis of Variance ; Asbestos/*adverse effects ; Evaluation Studies as Topic ; Female ; Humans ; Incidence ; Italy/epidemiology ; Lung/pathology ; Male ; Mesothelioma/diagnosis/epidemiology/*etiology ; Middle Aged ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/diagnosis/epidemiology/*etiology ; Surveys and Questionnaires ; Survival Rate ; }, abstract = {Latency periods (time intervals elapsing between first exposure to asbestos and death) were examined in 421 cases of malignant pleural mesothelioma, diagnosed in the Trieste-Monfalcone area, Italy. Occupational data were collected from the patients or from their relatives by personal or telephone interviews. Routine lung sections were examined for asbestos bodies in 370 cases. Latency periods, calculated in 312 cases, ranged from 14 to 72 years (mean 48.7, median 51). Latency periods differed significantly from one occupational group to another. Mean latency periods were 29.6 among insulators, 35.4 among dock workers, 43.7 in a heterogeneous group defined as various, 46.4 in non-shipbuilding industry workers, 49.4 in shipyard workers, 51.7 among women with a history of domestic exposure to asbestos, and 56.2 in people employed in maritime trades. The ANOVA test indicated a correlation between latency periods and occupational groups. Latency periods in people with asbestos bodies visible in routine lung sections did not differ from those seen in cases with no evidence of asbestos bodies. These data suggest that intensity of exposure is a relevant, but not the only, factor in determining the duration of latency periods.}, } @article {pmid9167230, year = {1997}, author = {Karjalainen, A}, title = {Asbestos--a continuing concern.}, journal = {Scandinavian journal of work, environment & health}, volume = {23}, number = {2}, pages = {81-82}, doi = {10.5271/sjweh.184}, pmid = {9167230}, issn = {0355-3140}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Female ; Finland/epidemiology ; Health Policy ; Humans ; Lung Neoplasms/epidemiology/*prevention & control ; Male ; Mesothelioma/epidemiology/*prevention & control ; Middle Aged ; Occupational Exposure/*adverse effects ; Population Surveillance ; Workers' Compensation ; }, } @article {pmid9146459, year = {1997}, author = {Mossman, BT and Gee, JB}, title = {Asbestos-related cancer and the amphibole hypothesis. The hypothesis is still supported by scientists and scientific data.}, journal = {American journal of public health}, volume = {87}, number = {4}, pages = {689-90; author reply 690-1}, pmid = {9146459}, issn = {0090-0036}, mesh = {Asbestos, Amphibole/*toxicity ; Humans ; Mesothelioma/*chemically induced ; Pleural Neoplasms/*chemically induced ; }, } @article {pmid9146458, year = {1997}, author = {Langer, AM and Nolan, RP}, title = {Asbestos-related cancer and the amphibole hypothesis. The amphibole hypothesis: neither gone nor forgotten.}, journal = {American journal of public health}, volume = {87}, number = {4}, pages = {688-9; author reply 690-1}, pmid = {9146458}, issn = {0090-0036}, mesh = {Asbestos, Amphibole/*toxicity ; Humans ; Mesothelioma/*chemically induced ; Pleural Neoplasms/*chemically induced ; South Africa ; }, } @article {pmid9146457, year = {1997}, author = {Wagner, JC}, title = {Asbestos-related cancer and the amphibole hypothesis. The first documentation of the association.}, journal = {American journal of public health}, volume = {87}, number = {4}, pages = {687-688}, pmid = {9146457}, issn = {0090-0036}, mesh = {Asbestos, Amphibole/*toxicity ; Humans ; Mesothelioma/*chemically induced ; Pleural Neoplasms/*chemically induced ; South Africa ; }, } @article {pmid9111221, year = {1997}, author = {Fung, H and Kow, YW and Van Houten, B and Mossman, BT}, title = {Patterns of 8-hydroxydeoxyguanosine formation in DNA and indications of oxidative stress in rat and human pleural mesothelial cells after exposure to crocidolite asbestos.}, journal = {Carcinogenesis}, volume = {18}, number = {4}, pages = {825-832}, doi = {10.1093/carcin/18.4.825}, pmid = {9111221}, issn = {0143-3334}, support = {ESO7038/ES/NIEHS NIH HHS/United States ; }, mesh = {8-Hydroxy-2'-Deoxyguanosine ; Animals ; Asbestos, Crocidolite/*toxicity ; Blood ; Carcinogens/*pharmacology ; Cell Cycle/drug effects ; Cell Line ; Cell Survival/drug effects ; Culture Media ; DNA/*drug effects/metabolism ; Deoxyguanosine/*analogs & derivatives/biosynthesis ; Epithelial Cells ; Epithelium/drug effects/metabolism ; Gene Expression Regulation, Enzymologic/drug effects ; Humans ; Iron Chelating Agents ; *Oxidative Stress ; Pleura/cytology/*drug effects/metabolism ; Rats ; Rats, Inbred F344 ; Superoxide Dismutase/genetics ; }, abstract = {Oxidative damage is a proposed mechanism of asbestos-induced carcinogenesis, but the detection of oxidative DNA lesions in target cells of asbestos-induced mesothelioma has not been examined. In studies here, DNA was isolated from both rat pleural mesothelial (RPM) cells and a human mesothelial cell line (MET5A) after exposure in vitro to crocidolite asbestos at various concentrations. DNA was then examined for formation of 8-hydroxydeoxyguanosine (8-OHdG) at 24, 48 and 72 h using HPLC with electrochemical detection. In addition, steady-state mRNA levels of manganese-containing superoxide dismutase (MnSOD) were assessed as an indication of oxidative stress. Whereas RPM cells showed dose-dependent and significant increases in 8-OHdG formation in response to crocidolite asbestos or iron-chelated crocidolite fibers (but not after exposure to glass beads), MET5A cells showed decreases in 8-OHdG. Both cell types exhibited elevations in message levels of MnSOD. In comparison with human MET5A cells, RPM cells exhibited increased cytotoxicity and apoptosis in response to asbestos, as documented by cell viability assays and flow cytometry analysis using propidium iodide. Results in RPM cells indicate that asbestos causes oxidative damage that may result in potentially mutagenic lesions in DNA and/or apoptosis, despite compensatory increases in expression of an antioxidant enzyme.}, } @article {pmid9139208, year = {1997}, author = {Türler, A and Mönig, SP and Raab, M}, title = {[Problems in diagnosis and therapy of malignant pleural mesothelioma].}, journal = {Medizinische Klinik (Munich, Germany : 1983)}, volume = {92}, number = {2}, pages = {101-105}, pmid = {9139208}, issn = {0723-5003}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Mesothelioma/*diagnosis/pathology/surgery ; Middle Aged ; Neoplasm Staging ; Palliative Care ; Pleura/pathology ; Pleural Neoplasms/*diagnosis/pathology/surgery ; Pneumonectomy ; Prognosis ; }, abstract = {The incidence of malignant pleural mesothelioma increased continuously during recent years. This is related to widespread use and processing of asbestos in the last decades. Characteristical symptoms like dyspnea, cough and thoracic pain are common in almost all pulmonal diseases. Therefore the possible occurrence of a pleural tumor is often neglected. This leads to a delay between onset of symptoms and the establishment of diagnosis. With X-ray and computed tomography 80% of the pleural tumors can be proved. Only in few cases the histopathological analysis of the pleural fluid leads to diagnosis. However, thoracoscopy or thoracotomy remain the most reliable means of obtaining a definitive tissue diagnosis. At the time of operation advanced stages are found in many cases, therefore palliative surgery is indicated. Due to high morbidity and mortality pleuropneumonectomy should be done only in selected patients. Pleurectomy or pleurodesis is often sufficient to release patients' symptoms. Chemotherapy and radiation have not proven effective in controlling malignant mesothelioma. In conclusion pleural mesothelioma remains a tumor with a very poor prognosis. Long term survival is occasional even in case of multimodal treatment.}, } @article {pmid9094189, year = {1997}, author = {Berti, E and Schiaffino, E and Minervini, MS and Longo, G and Schmid, C}, title = {Primary malignant mesothelioma of the tunica vaginalis of the testis. Immunohistochemistry and electron microscopy.}, journal = {Pathology}, volume = {29}, number = {1}, pages = {96-99}, doi = {10.1080/00313029700169654}, pmid = {9094189}, issn = {0031-3025}, mesh = {Aged ; Flow Cytometry ; Humans ; Immunohistochemistry ; Male ; Mesothelioma/*chemistry/ultrastructure ; Microscopy, Electron ; Testicular Neoplasms/*chemistry/ultrastructure ; }, abstract = {A case of primary malignant mesothelioma of the tunica vaginalis of the testis in a 75 year old man is here presented. Anamnesis for asbestos exposure was negative. Recurrent left hydrocele was the main symptom. Echography revealed a nodular mass in the caudal aspect of the epididymis and papillary projection on the surface of the tunica vaginalis of the testis. An inguinal left orchiectomy was performed. The tumor both in the solid area and in the papillary projections was identified as a malignant mesothelioma of epithelial type. The role of immunohistochemistry and ultrastructure for a correct definition of the tumor is underlined.}, } @article {pmid9042171, year = {1997}, author = {King, JA and Tucker, JA and Wong, SW}, title = {Mesothelioma: a study of 22 gases.}, journal = {Southern medical journal}, volume = {90}, number = {2}, pages = {199-205}, doi = {10.1097/00007611-199702000-00006}, pmid = {9042171}, issn = {0038-4348}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Coloring Agents ; Female ; Humans ; Male ; Mesothelioma/etiology/*pathology ; Middle Aged ; Neoplasm Metastasis ; Occupations ; }, abstract = {Mesothelioma is a rare, asbestos-associated tumor that infrequently metastasizes. We reviewed 22 autopsies (from February 1989 through July 1994) showing mesothelioma. We determined distribution of metastases and staining characteristics of primary mesotheliomas compared to tissue involved by metastases and/or direct extension. Mean patient age was 68 years (range, 38 to 88 years); black:white patient ratio, 4:18; and male:female patient ratio, 2:1. All patients had a history of asbestos exposure. Fifteen autopsies were complete and 7 were limited to the thoracic cavity. Multiple sites were involved by direct extension. Metastases were in multiple sites, including omentum, stomach, intestine, mesentery, adrenal glands, ovary, pancreas, kidneys, liver, spleen, and vertebrae. Results of immunohistochemical staining of primary mesotheliomas and metastases were similar; both were positive for low-molecular-weight keratin and negative for carcinoembryonic antigen, Leu-M1, Ber-EP4, and periodic acid-Schiff reagent with diastase. Results of testing for high-molecular-weight keratin were variable.}, } @article {pmid9028434, year = {1997}, author = {Stern, FB and Sweeney, MH and Ward, E}, title = {Proportionate mortality among unionized construction ironworkers.}, journal = {American journal of industrial medicine}, volume = {31}, number = {2}, pages = {176-187}, doi = {10.1002/(sici)1097-0274(199702)31:2<176::aid-ajim7>3.0.co;2-y}, pmid = {9028434}, issn = {0271-3586}, mesh = {Accidents, Occupational/mortality ; Adult ; Aged ; *Cause of Death ; Cerebrovascular Disorders/mortality ; Female ; Humans ; *Iron ; Kidney Diseases/mortality ; Male ; *Metallurgy ; Middle Aged ; Neoplasms/mortality ; Occupations ; Wounds and Injuries/mortality ; }, abstract = {This report presents the results of proportionate mortality ratios (PMR) and proportionate cancer mortality ratios (PCMR) among 13,301 members of the International Union of Bridge, Structural, and Ornamental Ironworkers who had been members for a minimum of 1 year, were actively paying dues into the death beneficiary fund, and had died between 1984-1991. Using the United States proportionate mortality rates as the comparison population, statistically significant elevated risks, using 95% confidence intervals (CI), were observed for several types of injuries: falls (N = 259, PMR = 3.57, CI = 3.15-4.03), transportation injuries (N = 363, PMR = 1.22, CI = 1.10-1.35), and other types of injuries (N = 225, PMR = 1.63, CI = 1.43-1.86). The deaths due to falls were significantly elevated for each 10-year age group under age 60 (PMR > 7.00) and for those workers with < 20 years in the union (PMR > 6.00). Elevated mortality risks were also observed for all malignant neoplasms combined (N = 3,682, PMR = 1.09, CI = 1.06-1.13) as well as for site-specific malignant neoplasms of the lung (N = 1,523, PMR = 1.28, CI = 1.21-1.35), pleural mesothelioma (N = 7, PMR = 1.67, CI = 0.67-3.44) and "other and unspecified sites" (N = 307, PMR = 1.29, CI = 1.15-1.44). The category "pneumoconiosis and other respiratory diseases" was also significantly elevated (N = 690, PMR = 1.11, CI = 1.03-1.20); in this category, deaths due to asbestosis had the greatest elevated risk (N = 10, PMR = 3.56, CI = 1.70-6.54). No elevation in risk was found for kidney cancer or for chronic nephritis which were of interest because of Ironworkers' potential exposure to lead. The present study underscores the importance of fall protection and other injury prevention efforts in the construction industry, as well as the need to control airborne exposures to asbestos, welding fumes and other respirable disease hazards.}, } @article {pmid9012593, year = {1997}, author = {Price, B}, title = {Analysis of current trends in United States mesothelioma incidence.}, journal = {American journal of epidemiology}, volume = {145}, number = {3}, pages = {211-218}, doi = {10.1093/oxfordjournals.aje.a009093}, pmid = {9012593}, issn = {0002-9262}, mesh = {Aged ; Asbestos/adverse effects ; Cohort Studies ; Female ; Forecasting ; Humans ; Incidence ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Exposure ; Peritoneal Neoplasms/*epidemiology/etiology ; Pleural Neoplasms/*epidemiology/etiology ; Regression Analysis ; SEER Program ; United States/epidemiology ; }, abstract = {Mesothelioma incidence often is interpreted as an index of past exposure to airborne asbestos. The mesothelioma rate for US males exhibits an increasing trend throughout the 1970s and early 1980s. The trend has been attributed to occupational exposure in the shipbuilding industry during World War II, in manufacturing, and in building construction. Incidence data (1973-1992) from the Surveillance, Epidemiology, and End Results Program were used to investigate current trends in age-adjusted and age-specific mesothelioma rates. An age and birth-cohort model was used to project both lifetime probabilities of mesothelioma by cohort and the annual number of cases expected over the next 70 years. The current trend in female rates is flat (age-adjusted rate = 0.30 per 100,000). The estimated lifetime risk for females is 2.5 x 10(-4), independent of birth cohort. The projected average annual number of female cases is 500. For males, the age-adjusted mesothelioma rate is increasing solely due to the age group 75 years and over, albeit at a declining growth rate. Lifetime risk for males peaks at 2 x 10(-3) for the 1925-1929 birth cohort, then decreases to 5 x 10(-4) for the 1955-1959 birth cohort. The pattern of rates reflected in the age and birth-cohort model suggests a peak in the annual number of mesothelioma cases for males at 2,300 before the year 2000. The number of male cases then will drop during the next 50-60 years toward 500. These trends mirror the US trend in raw asbestos consumption and a reduction in workplace airborne asbestos levels.}, } @article {pmid9064836, year = {1997}, author = {Wergeland, E and Bjerkedal, T and Andersen, A and Mowé, G}, title = {[Use of occupational disease benefits].}, journal = {Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke}, volume = {117}, number = {2}, pages = {211-216}, pmid = {9064836}, issn = {0029-2001}, mesh = {Adult ; Aged ; Female ; Humans ; *Insurance, Disability ; Male ; Mesothelioma/*economics/etiology ; Middle Aged ; Norway ; Occupational Diseases/*economics/etiology ; Pleural Neoplasms/*economics/etiology ; *Workers' Compensation ; }, abstract = {Persons with pleuramesothelioma were studied to find out the share receiving occupational injury benefit from the National Insurance Scheme. This disease, caused by inhaling asbestos, was chosen because it has been estimated that between 70 and 80 per cent of persons with pleuramesothelioma fulfil the criteria for compensation. During the period 1970-93, 662 men and 104 women were recorded as having this disease. Up to June 1996, the National Insurance Administration had considered the cases of only 163 men, and no women. A further 25-30 patients may have filed claims with the local national insurance office. This implies that, overall, maximum one third of those entitled to occupational injury benefit have received it. The fraction would probably be even lower in the case of diseases where the association with occupation is less certain. It is recommended that national disease registries, such as the Cancer Registry, should report possible cases of occupational disease to the National Insurance Administration.}, } @article {pmid9575374, year = {1997}, author = {Roggli, VL and Oury, TD and Moffatt, EJ}, title = {Malignant mesothelioma in women.}, journal = {Anatomic pathology (Chicago, Ill. : annual)}, volume = {2}, number = {}, pages = {147-163}, pmid = {9575374}, issn = {1056-5884}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos, Amosite/analysis ; Asbestos, Amphibole/analysis ; Asbestos, Serpentine/analysis ; Asbestosis/*pathology ; Female ; Humans ; Male ; Mesothelioma/*pathology ; Middle Aged ; Mineral Fibers/analysis ; Peritoneal Neoplasms/*pathology ; Peritoneum/*pathology ; Pleura/*pathology ; Pleural Neoplasms/*pathology ; }, abstract = {About 8% of our cases of mesothelioma occur in women, with a median age of 59 years. Our percentage is lower than other series reported in the literature because of the large number of occupationally exposed men referred to our laboratory. Tumor arose in the pleura in 86% of the women in our study, and the majority were epithelial. Pleural plaques were found in half of the women for which this information was available, and asbestosis was found in only 16%. A history of exposure to asbestos was identified in three quarters of the women, more than half of whom were household contacts of asbestos workers. Occupational exposure to asbestos was identified in only 19% of patients. An elevated tissue asbestos burden was noted in 70% of women from whom lung tissue was available for analysis. The main fiber type identified was amosite, followed by tremolite and chrysotile. These findings and those from other countries suggest a need for reassessment of the background rate of mesothelioma in industrialized nations.}, } @article {pmid9501330, year = {1997}, author = {Szeszenia-Dabrowska, N and Wilczyńska, U and Szymczak, W}, title = {[Cancer risk in asbestos-cement industry workers in Poland].}, journal = {Medycyna pracy}, volume = {48}, number = {5}, pages = {473-483}, pmid = {9501330}, issn = {0465-5893}, mesh = {Aged ; Asbestos/*adverse effects/analysis ; Asbestos, Amosite/adverse effects/chemical synthesis ; Asbestos, Crocidolite/adverse effects/chemical synthesis ; Cohort Studies ; Environmental Monitoring ; Epidemiological Monitoring ; Female ; Humans ; Incidence ; Male ; Mesothelioma/epidemiology/etiology/mortality ; Middle Aged ; Neoplasms/*epidemiology/etiology ; Occupational Diseases/*epidemiology ; Pleural Neoplasms/epidemiology/etiology/mortality ; Poland/epidemiology ; Risk Assessment ; Sex Distribution ; Survival Rate ; }, abstract = {A cohort study was carried out in order to evaluate the cancer risk in the asbestos-cement industry workers. The cohort consisted of workers employed in four asbestos-cement plants. One of those plants was established in 1924, the other three in the 1960s and 1970s. Currently only two of these plants continue their production. The plants used mainly chrysotile asbestos as well as crocidolite and amosite. Amphibolite asbestos was used before the mid-nineteen eighties in production of pressure pipes utilising about 15% of the total quantity of asbestos used. The measurements of the asbestos fibre concentration at work-sites have been taken occasionally since the mid 1980s, thus, the determination of a cumulative dose for individual persons in the cohort and the evaluation of the dose-effect relationship were not feasible. It could only be supposed that the concentrations at the preparatory work-site during first years of the plants' operation accounted for several tens fibres/cm3 in the production that employed the dry method. The cohort consisted of workers employed in the plant for at least three months between beginning of the plant during the post-war period, and 1980, that is during the period when amphibolite asbestos was in use. The retrospective observation was completed on 31 December 1991. The analysis of the death risk by causes was based on a standardized mortality ratios (SMRs) calculated using the person-years method. Statistical significance of SMRs was assessed by means of Poisson distribution one-sided test. The general population of Poland was used as the reference population to estimate the death risk. The cohort comprised 4,712 persons (3,563 males and 1,149 females). Of this number 4,500 persons (3,405 males and 1,095 females) were followed. The cohort availability were 95.5%. Male mortality, both total (473 deaths; SMR = 83) and due to malignant neoplasms (108 deaths; SMR = 86) was lower than in the general population. An excess of deaths from neoplasm of the pleura was by about 23 times higher (5 deaths; SMR = 2,288) and from neoplasm of the large intestine by two times higher (7 deaths; SMR = 214). Among females (41 deaths; SMR = 50) death risk was lower than in the reference population. At a low level of total mortality from neoplasms (13 deaths; SMR = 52) a statistically significant excess of deaths from neoplasm of the pleura (2 deaths; SMR = 2,112) was observed. In the plants investigated the analysis revealed a considerably diversified mortality from asbestos-related neoplasms. The incidence of pleura mesothelioma should be attributed to the use of considerable quantities of crocidolite asbestos and high concentrations of fibres in the air in plants II and IV, particularly during the first years after their establishment. In view of a long period of latency the excess of this neoplasm can be expected till 2020.}, } @article {pmid9329647, year = {1997}, author = {Husgafvel-Pursiainen, K and Kannio, A and Oksa, P and Suitiala, T and Koskinen, H and Partanen, R and Hemminki, K and Smith, S and Rosenstock-Leibu, R and Brandt-Rauf, PW}, title = {Mutations, tissue accumulations, and serum levels of p53 in patients with occupational cancers from asbestos and silica exposure.}, journal = {Environmental and molecular mutagenesis}, volume = {30}, number = {2}, pages = {224-230}, pmid = {9329647}, issn = {0893-6692}, support = {CA69243/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Asbestosis/*genetics ; Base Sequence ; Electrophoresis/methods ; Humans ; Lung Neoplasms/genetics/metabolism ; Male ; Mesothelioma/genetics/metabolism ; Middle Aged ; Molecular Sequence Data ; *Mutation ; Neoplasms/epidemiology/*genetics ; Occupational Exposure ; Silicosis/*genetics ; Tumor Suppressor Protein p53/*blood/genetics/metabolism ; }, abstract = {In order to determine the relationship between mutations, tissue accumulations, and serum levels of p53 in occupational cancers, we used denaturing gradient gel electrophoresis and DNA sequencing of exons 5-9 of the p53 gene, immunohistochemical analysis for tissue identification of mutant p53 protein, and enzyme-linked immunosorbent assay for serum levels of mutant p53 protein to examine for such alteration in a cohort of individuals with workplace exposure to asbestos or silica, and resultant lung cancers or mesotheliomas. DNA analysis detected mutations in 5 of 18 (28%) tumors, and tissue accumulations of protein were detected in 7 of 20 (35%) tumors; the agreement between mutational and immunohistochemical analyses was significant (kappa = 0.62, P = 0.002). Serum elevations of protein were detected in 4 of 11 (36%) cases with available serum samples; the agreement between tissue alterations and serum elevations was also significant (kappa = 0.71, P = 0.017). In addition, based on the analysis of banked samples, serum results tended to be consistent over time prior to the diagnosis of disease (positive predictive value = 0.67, negative predictive value = 0.83). These results suggest that serum levels of p53 are reasonably accurate in reflecting tissue alterations in p53 at the gene and/ or protein level and may be early biomarkers of disease risk.}, } @article {pmid9198711, year = {1997}, author = {Szeszenia-Dabrowska, N and Strzelecka, A and Wilczyńska, U and Szymczak, W}, title = {[Occupational neoplasms in Poland in the years 1971-1994].}, journal = {Medycyna pracy}, volume = {48}, number = {1}, pages = {1-14}, pmid = {9198711}, issn = {0465-5893}, mesh = {Adolescent ; Adult ; Air Pollutants, Occupational/*adverse effects ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Neoplasms/classification/*epidemiology/etiology ; Occupational Diseases/classification/*epidemiology ; Poland/epidemiology ; Sex Distribution ; }, abstract = {The analysis of the incidence of malignant neoplasms, recognised as occupational disease, in Poland during the years 1971-94 was based on occupational disease certificates sent obligatory to the Nofer institute of Occupational Medicine (Lódz) by all sanitary and epidemiological stations under the Ministry of Health and Social Welfare and the Polish State Railways. During the period study 1118 occupational neoplasms were diagnosed, including 1042 cases (93.2%) of neoplasms in males. Among males malignant Ineoplasms of lung (36.1%), larynx (25.5%), bladder (14.7), skin (6%), lymphatic and haematopoietic tissue (3.4%) and pleura (2.9%) were most common. The rate occupational neoplasms in the total number of neoplasms registered accounted for 0.11% in males and 0.01% in females. PAH (29.1%), asbestos dust (18.8%), ionizing radiation (13.8%), chromium and its compounds (13.5%) and benzidine (9.8%) belong to the most frequent causes of malignant neoplasms in males, and ionizing radiation (31.5%) and asbestos dust (30.3%) in females. The number of neoplasms recognised as occupational disease is very low. Underestimation of occupational neoplasms is very common throughout the world, but it is particularly high in Poland if we take the incidence of pleura mesothelioma as an example. This is mainly due to: (1) the lack of clinical and morphological specificity of occupationally induced neoplasms; (2) a long latency; (3) the influence of other factors confounding the effect of occupational exposure; (4) a relatively small number of occupational carcinogens identified thus far; (5) limited knowledge of occupational carcinogens and criteria for occupational disease certification, and unsatisfactory interviewing skills among doctors who diagnose cancer disease. The identification of a harmful factor and the size of exposure to it, belongs to the weakest point in certifying the occupational background of the disease. The essential conclusions presented stress the urgent need for establishing the system facilitating the diagnosis and certification of occupational neoplasms.}, } @article {pmid9091974, year = {1997}, author = {Ryan, PJ and Oates, JL and Crocker, J and Stableforth, DE}, title = {Distinction between pleural mesothelioma and pulmonary adenocarcinoma using MOC31 in an asbestos sprayer.}, journal = {Respiratory medicine}, volume = {91}, number = {1}, pages = {57-60}, doi = {10.1016/s0954-6111(97)90137-2}, pmid = {9091974}, issn = {0954-6111}, mesh = {Adenocarcinoma/*diagnosis ; *Antibodies, Monoclonal ; Diagnosis, Differential ; Humans ; Immunohistochemistry ; Lung Neoplasms/*diagnosis ; Male ; Mesothelioma/*diagnosis ; Middle Aged ; Pleural Neoplasms/*diagnosis ; }, abstract = {Asbestos exposure may cause asbestosis, pleural plaques and benign pleural disease, and may pre-dispose to malignant mesothelioma and other neoplasms. The occurrence to two primary tumours in the same patient is rare, and the appearance of a pleural mesothelioma and another lung tumour is exceptional. The present case report describes a patient who, by standard immunohistochemistry, was thought to have mesothelioma at pleuro-pneumonectomy, and adenocarcinoma in the other lung at post-mortem 5 months later. Subsequent investigation using the MOC31 antibody demonstrated a single pathology of adenocarcinoma of the lung. The additional use of this antibody has important histopathological and legal implications.}, } @article {pmid9090524, year = {1997}, author = {Little, M and Wells, C}, title = {A clinical overview of WT1 gene mutations.}, journal = {Human mutation}, volume = {9}, number = {3}, pages = {209-225}, doi = {10.1002/(SICI)1098-1004(1997)9:3<209::AID-HUMU2>3.0.CO;2-2}, pmid = {9090524}, issn = {1059-7794}, mesh = {Alleles ; Beckwith-Wiedemann Syndrome/genetics ; Chromosome Deletion ; Chromosomes, Human, Pair 11 ; Cryptorchidism/genetics ; Disorders of Sex Development/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Genes, Tumor Suppressor ; *Genes, Wilms Tumor ; Humans ; Intellectual Disability/genetics ; Kidney Neoplasms/*genetics ; Male ; *Mutation ; Neoplasms/genetics ; Nephrotic Syndrome/genetics ; WAGR Syndrome/*genetics ; X Chromosome ; }, abstract = {Mutations in the WT1 gene were anticipated to explain the genetic basis of the childhood kidney cancer, Wilms tumour (WT). Six years on, we review 100 reports of intragenic WT1 mutations and examine the accompanying clinical phenotypes. While only 5% of sporadic Wilms' tumours have intragenic WT1 mutations, > 90% of patients with the Denys-Drash syndrome (renal nephropathy, gonadal anomaly, predisposition to WT) carry constitutional intragenic WT1 mutations. WT1 mutations have also been reported in juvenile granulosa cell tumour, non-asbestos related mesothelioma, desmoplastic small round cell tumour and, most recently, acute myeloid leukemia.}, } @article {pmid9072948, year = {1997}, author = {Liddell, FD}, title = {Magic, menace, myth and malice.}, journal = {The Annals of occupational hygiene}, volume = {41}, number = {1}, pages = {3-12}, doi = {10.1016/S0003-4878(96)00177-9}, pmid = {9072948}, issn = {0003-4878}, mesh = {Animals ; Asbestos/*history ; Asbestosis/*history ; Carcinogens/*history ; History, 19th Century ; History, 20th Century ; History, Ancient ; Humans ; Mesothelioma/history ; Occupational Exposure/*history ; }, } @article {pmid9072947, year = {1997}, author = {Liddell, FD and McDonald, AD and McDonald, JC}, title = {The 1891-1920 birth cohort of Quebec chrysotile miners and millers: development from 1904 and mortality to 1992.}, journal = {The Annals of occupational hygiene}, volume = {41}, number = {1}, pages = {13-36}, doi = {10.1016/S0003-4878(96)00044-0}, pmid = {9072947}, issn = {0003-4878}, mesh = {Aged ; Air Pollutants, Occupational/*adverse effects ; Asbestos, Serpentine/*adverse effects ; Asbestosis/etiology/*mortality ; Cause of Death ; Cohort Studies ; Environmental Monitoring ; Epidemiological Monitoring ; Humans ; Male ; Mesothelioma/etiology/mortality ; Mining/*statistics & numerical data ; Neoplasms/etiology/*mortality ; Quebec/epidemiology ; }, abstract = {This paper draws together the mortality experience for a cohort of some 11000 male Quebec Chrysotile miners and millers, reported at intervals since 1971 and now again updated. Of the 10918 men in the complete cohort, 1138 were lost to view, almost all never traced after employment of only a month or two before 1935; the other 9780 men were traced into 1992. Of these, 8009 (82%) are known to have died: 657 from lung cancer, 38 from mesotheliona, 1205 from other malignant disease, 108 from pneumoconiosis and 561 from other non-malignant respiratory diseases (excluding tuberculosis). After early fluctuations. SMRs (all causes) against Quebec rates have been reasonably steady since about 1945. For men first employed in Asbestos, mine or factory, they were very much what might have been expected for a blue collar population without any hazardous exposure. SMRs in the Thetford Mines area were almost 8% higher, but in line with anecdotal evidence concerning socio-economic status. At exposures below 300 (million particles per cubic foot) x years, (mpcf.y), equivalent to roughly 1000 (fibres/ml) x years-or, say, 10 years in the 1940s at 80 (fibres/ml)-findings were as follows. There were no discernible associations of degree of exposure and SMRs, whether for all causes of death or for all the specific cancer sites examined. The average SMRs were 1.07 (all causes), and 1.16, 0.93, 1.03 and 1.21, respectively, for gastric, other abdominal, laryngeal and lung cancer. Men whose exposures were less then 300 mpcf.y suffered almost one-half of the 146 deaths from pneumoconiosis or mesothelioma; the elimination of these two causes would have reduced these men's SMR (all causes) from 1.07 to approximately 1.06. Thus it is concluded from the viewpoint of mortality that exposure in this industry to less than 300 mpcf.y has been essentially innocuous, although there was a small risk or pneumoconiosis or mesothelioma. Higher exposures have, however, led to excesses, increasing with degree of exposure, of mortality from all causes, and from lung cancer and stomach cancer, but such exposures, of at least 300 mpcf.y, are several orders of magnitude more severe than any that have been seen for many years. The effects of cigarette smoking were much more deleterious than those of dust exposure, not only for lung cancer (the SMR for smokers of 20+ cigarettes a day being 4.6 times higher than that for non-smokers), but also for stomach cancer (2.0 times higher), laryngeal cancer (2.9 times higher), and-most importantly-for all causes (1.6 times higher).}, } @article {pmid9072041, year = {1997}, author = {Greenberg, M}, title = {Mesothelioma in a community in the north of England.}, journal = {Occupational and environmental medicine}, volume = {54}, number = {1}, pages = {67-68}, pmid = {9072041}, issn = {1351-0711}, mesh = {*Asbestos ; Bias ; Dust/adverse effects ; England/epidemiology ; Humans ; Lung Neoplasms/*epidemiology ; Occupational Exposure/*adverse effects ; }, } @article {pmid9051694, year = {1997}, author = {Sakuma, N and Kamei, T and Unoki, T and Okamura, H and Ishihara, T}, title = {An autopsy case of diffuse malignant mesothelioma of the pericardium.}, journal = {Pathology international}, volume = {47}, number = {1}, pages = {64-67}, doi = {10.1111/j.1440-1827.1997.tb04436.x}, pmid = {9051694}, issn = {1320-5463}, mesh = {Aged ; Heart Neoplasms/chemistry/*pathology ; Histocytochemistry ; Humans ; Male ; Mesothelioma/chemistry/*pathology ; Pericardial Effusion/metabolism/*pathology ; }, abstract = {A report is presented of an autopsy case of a 71-year-old Japanese man with a diffuse malignant epithelial mesothelioma of the pericardium with massive pericardial effusion and a thickened pericardium. He had no history of exposure to asbestos. He suffered severe heart failure and later died. Autopsy revealed that the tumor had developed over the pericardium. Microscopically, the tumor cells were arranged in an epithelial form, and histochemically, the cytoplasm of these cells contained glycogen and hyaluronic acid. The tumor tissue showed immunohistochemical positivity for cytokeratin, epithelial membrane antigen, vimentin, cancer antigen 125, thrombomodulin, mesothelial antigen, muscle actin and human milk fat globule. In contrast, all the tumor cells were negative for human carcinoembryonic antigen and epithelial antigen. Ultrastructurally, the tumor cells had long, thin microvilli, abundant intermediate filaments, intracytoplasmic lumina and long desmosomes. It is considered that the patient had a typical malignant epithelial mesothelioma of the pericardium.}, } @article {pmid9022813, year = {1997}, author = {Kleymenova, EV and Bianchi, AA and Kley, N and Pylev, LN and Walker, CL}, title = {Characterization of the rat neurofibromatosis 2 gene and its involvement in asbestos-induced mesothelioma.}, journal = {Molecular carcinogenesis}, volume = {18}, number = {1}, pages = {54-60}, pmid = {9022813}, issn = {0899-1987}, support = {ES06658/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Asbestos ; Base Sequence ; Blotting, Northern ; DNA ; Genes, Neurofibromatosis 2 ; Humans ; Mesothelioma/etiology/*genetics ; Molecular Sequence Data ; Mutation ; Peritoneal Neoplasms/etiology/*genetics ; Polymerase Chain Reaction ; Polymorphism, Single-Stranded Conformational ; RNA Splicing ; Rats ; Tumor Cells, Cultured ; }, abstract = {The neurofibromatosis 2 (NF2) tumor suppressor gene was recently implicated in the genesis of human mesothelioma. To investigate the role of this tumor suppressor gene in rat asbestos-induced mesothelioma, a commonly used model for the human disease, we characterized the rat homologue of NF2 and examined rat chrysotile-induced primary mesotheliomas and cell lines derived from chrysotile- and crocidolite-induced mesotheliomas for alterations in this gene. The coding sequence obtained for the rat NF2 gene had 90% nucleotide homology with the human NF2 gene. The rat NF2 gene was ubiquitously expressed as a 4.4-kb transcript in normal rat tissues as well as in rat mesothelioma cell lines. Reverse transcription-polymerase chain reaction analysis to examine splicing of NF2 exons in mesothelioma cells indicated that the exon splicing pattern was similar in normal and neoplastic cells. To determine if mutations had occurred in the NF2 coding region in rat mesotheliomas, single-strand conformation polymorphism analysis and direct sequencing were used to screen 10 primary tumors and six tumor cell lines. No DNA sequence alterations were observed in any of the rat mesothelioma samples examined. These findings contrast with data reported previously for human mesotheliomas, in which the NF2 gene was found to be mutated in 40% of cases. Taken together, these data suggest that the role of NF2 in the development of rodent asbestos-induced mesothelioma may differ significantly from the role in the human disease.}, } @article {pmid8996002, year = {1997}, author = {Renshaw, AA and Dean, BR and Antman, KH and Sugarbaker, DJ and Cibas, ES}, title = {The role of cytologic evaluation of pleural fluid in the diagnosis of malignant mesothelioma.}, journal = {Chest}, volume = {111}, number = {1}, pages = {106-109}, doi = {10.1378/chest.111.1.106}, pmid = {8996002}, issn = {0012-3692}, mesh = {Adult ; Aged ; Aged, 80 and over ; Chromosome Aberrations ; Female ; Humans ; Male ; Mesothelioma/*pathology ; Middle Aged ; Pleural Effusion/*pathology ; Pleural Neoplasms/*pathology ; Retrospective Studies ; Sensitivity and Specificity ; }, abstract = {STUDY OBJECTIVE: Treatment of malignant mesothelioma (MM) at an early stage results in increased survival. Cytologic examination of pleural effusions is one of the first diagnostic techniques attempted in these patients. The objective of this study was to define the role of cytologic examination of pleural fluid in facilitating early diagnosis.

DESIGN: The medical records and cytologic slides of patients with pleural MM were reviewed.

SETTING: Medical records were reviewed from two institutions: a large general hospital and a cancer hospital.

PATIENTS: Twenty-nine patients ranging in age from 32 to 81 years (mean, 59 years) met the study criteria.

INTERVENTIONS: All patients had at least one cytologic pleural fluid examination.

MEASUREMENTS AND RESULTS: The median time from initial symptoms to the diagnosis of MM was 8 weeks for all patients. For patients with a positive or suspicious cytologic result, the median was 4 weeks, and in those with a negative cytologic result, it was 12 weeks. The overall sensitivity of cytologic examination for the diagnosis of MM was 32%. Cytogenetic analysis of pleural fluid had a sensitivity of 56%, and was positive in 1 case in which results of cytologic examination were negative. Patients in whom the time from presentation to diagnosis was greater than 1 year all had negative cytologic results followed by long periods without further workup, despite a history of exposure to asbestos.

CONCLUSIONS: A positive or suspicious cytologic result was associated with a decreased median time to diagnosis. Unfortunately, the sensitivity of cytologic examination for a diagnosis of MM was only 32%. Until better diagnostic techniques are developed, we recommend immediate pleural biopsy in patients in whom MM is suspected and cytologic evaluation of pleural fluid gives negative results.}, } @article {pmid8961976, year = {1996}, author = {Hirvonen, A and Saarikoski, ST and Linnainmaa, K and Koskinen, K and Husgafvel-Pursiainen, K and Mattson, K and Vainio, H}, title = {Glutathione S-transferase and N-acetyltransferase genotypes and asbestos-associated pulmonary disorders.}, journal = {Journal of the National Cancer Institute}, volume = {88}, number = {24}, pages = {1853-1856}, doi = {10.1093/jnci/88.24.1853}, pmid = {8961976}, issn = {0027-8874}, mesh = {Acetylation ; Adult ; Arylamine N-Acetyltransferase/*genetics ; Asbestos/*adverse effects ; Cohort Studies ; DNA Probes ; Disease Susceptibility ; Finland ; *Gene Deletion ; Genotype ; Glutathione Transferase/*genetics ; Homozygote ; Humans ; Lung Diseases/chemically induced/*enzymology/*genetics ; Lung Neoplasms/enzymology/genetics ; Middle Aged ; Occupational Diseases/chemically induced/*enzymology/*genetics ; Occupational Exposure/*adverse effects ; Odds Ratio ; Polymorphism, Genetic ; Risk ; }, abstract = {BACKGROUND: Humans vary in their ability to metabolize endogenous and exogenous compounds. Glutathione S-transferases (GSTs) and N-acetyltransferases (NATs) are enzymes involved in the detoxification of hazardous agents. The GSTM1 and GSTT1 genes exhibit null (i.e., deletion) polymorphisms; in specific individuals, homozygous deletion (i.e., both copies lost) of these genes can be detected. Polymorphism of the NAT2 gene results in slow and fast acetylators of potentially toxic substances. The GSTM1-null and the NAT2 slow-acetylator genotypes have been associated with increased risks for the development of environmentally induced cancers.

PURPOSE: We assessed whether homozygous GSTM1-null or GSTT1-null genotypes or the NAT2 slow-acetylator genotype were associated with increased risks for the development of malignant and nonmalignant asbestos-related pulmonary disorders in a cohort of Finnish construction workers.

METHODS: The study population consisted of 145 asbestos insulators who were classified as having been exposed to high levels of asbestos; 69 of these individuals had no pulmonary disorders (control subjects), and 76 had either malignant mesothelioma (n = 24) or nonmalignant pulmonary disorders, such as asbestosis and/or pleural plaques (n = 52). Lymphocyte DNA and the polymerase chain reaction were used to determine the GSTM1, GSTT1, and NAT2 genotypes of the study subjects. Odds ratios (ORs) and 95% confidence intervals (CIs) estimating the relative risks of disease associated with specific genotypes were calculated from 2 x 2 tables by use of Fisher's exact method.

RESULTS: Risks for the development of asbestos-related pulmonary disorders were not affected significantly by homozygous deletion of the GSTM1 or GSTT1 genes. However, the risk of developing both malignant and nonmalignant pulmonary disorders for individuals with a NAT2 slow-acetylator genotype was more than twice that observed for those with a NAT2 fast-acetylator genotype (OR = 2.3; 95% CI = 1.1-4.7); the risk of developing malignant mesothelioma for NAT2 slow acetylators was increased almost fourfold (OR = 3.8; 95% CI = 1.2-14.3). Individuals who lacked the GSTM1 gene and possessed a NAT2 slow-acetylator genotype had a risk of developing malignant and nonmalignant pulmonary disorders that was approximately fivefold greater than that observed for those who had the GSTM1 gene and a NAT2 fast-acetylator genotype (OR = 5.1; 95% CI = 1.6-17.6); these individuals had a fourfold increased risk of developing nonmalignant pulmonary disorders (OR = 4.1; 95% CI = 1.1-17.2) and an eightfold increased risk of developing malignant mesothelioma (OR = 7.8; 95% CI = 1.4-78.7) when compared with the same reference group.

CONCLUSIONS: Individuals with homozygous deletion of the GSTM1 gene and a NAT2 slow-acetylator genotype who are exposed to high levels of asbestos appear to have enhanced susceptibility to asbestos-related pulmonary disorders.}, } @article {pmid8980698, year = {1996}, author = {Dönmez, H and Ozkul, Y and Uçak, R}, title = {Sister chromatid exchange frequency in inhabitants exposed to asbestos in Turkey.}, journal = {Mutation research}, volume = {361}, number = {2-3}, pages = {129-132}, doi = {10.1016/s0165-1161(96)90247-2}, pmid = {8980698}, issn = {0027-5107}, mesh = {Adult ; Aged ; Asbestos/*toxicity ; Calcinosis/chemically induced ; Female ; Humans ; Lung Neoplasms/chemically induced ; Male ; Mesothelioma/chemically induced ; Middle Aged ; Pleural Neoplasms/chemically induced ; Pulmonary Fibrosis/chemically induced ; *Sister Chromatid Exchange ; Turkey ; }, abstract = {Pleural mesothelioma, lung cancer, pleural calcification and fibrosis have been observed among inhabitants of the villages in Ivriz-Zanapa valley in Turkey. Earlier reports have stated that these endemic pathological conditions are caused by the inhalation of actinolite asbestos, a mineral commonly used indiscriminately to paint the walls and floors of houses. In the present study, 40 inhabitants in Yassikaya village in Ivriz-Zanapa valley and 20 controls were further investigated. The peripheral blood lymphocytes were cultured and harvested at 72 h for sister chromatid exchange (SCE) frequency. Inhabitants had a raised mean SCE rate compared with a control population.}, } @article {pmid9441114, year = {1996}, author = {Wang, NS}, title = {Pleural mesothelioma: an approach to diagnostic problems.}, journal = {Respirology (Carlton, Vic.)}, volume = {1}, number = {4}, pages = {259-271}, doi = {10.1111/j.1440-1843.1996.tb00041.x}, pmid = {9441114}, issn = {1323-7799}, mesh = {Asbestosis/*diagnosis/pathology ; Diagnosis, Differential ; Humans ; Immunohistochemistry ; Mesothelioma/*diagnosis/etiology/pathology ; Microscopy, Electron ; Pleural Neoplasms/*diagnosis/etiology/pathology ; }, abstract = {In the 1960s, a close relationship between heavy exposures to crocidolite asbestos and mesothelioma was established. The debate on the diagnosis of mesothelioma became complicated because of the possibility of litigation. Well differentiated mesothelioma cells are mucicarmine negative but alcian blue and periodic acid-Schiff (PAS) positive, which are removed by hyaluronidase and diastase digestion. By electron microscopy (EM), they show bush-like elongated, slender, and branching microvilli. By immunohistochemistry they express both keratin and vimentin but not carcinoembryonic antigenicity (CEA), B72.3, Ber-EP4, and Leu-M1. In poorly differentiated mesotheliomas, chromosomal and molecular biological alterations are common and complex but these alterations also overlap with that of poorly differentiated tumours of the lung and other organs. A poorly differentiated pleural tumour is most likely metastatic and needs good team work to locate the primary site. The diagnosis of a mesothelioma and asbestosis should be established separately. Future studies will be focused less on the phenotypic differences but more on the broad molecular and multi-phasic mechanisms of carcinogenesis, irrespective of the aetiological agents, in poorly differentiated tumours.}, } @article {pmid9022326, year = {1996}, author = {Hirano, K and Satoh, H and Inoue, M and Saitoh, T and Yazawa, T and Ohtsuka, M and Hasegawa, S}, title = {[Diffuse malignant mesothelioma associated with asbestos pleurisy].}, journal = {Nihon Kyobu Shikkan Gakkai zasshi}, volume = {34}, number = {12}, pages = {1390-1394}, pmid = {9022326}, issn = {0301-1542}, mesh = {Asbestos/*adverse effects ; Humans ; Male ; Mesothelioma/*etiology/pathology ; Middle Aged ; *Occupational Exposure ; Pleural Neoplasms/*etiology/pathology ; Pleurisy/*complications/pathology ; }, abstract = {Asbestos pleurisy is relatively uncommon among patients who present with pleural fluid. Association of diffuse malignant mesothelioma with asbestos pleurisy has not been reported in Japan, although 10 cases have been reported in the world literature. We encountered a 51-year-old man in whom diffuse malignant mesothelioma developed during a 5-year course of asbestos pleurisy. Mesothelial cells in patients with asbestos pleurisy are likely to be exposed to asbestos for a long time, which may increase the risk that mesothelioma will develop.}, } @article {pmid8994398, year = {1996}, author = {Dufresne, A and Bégin, R and Massé, S and Dufresne, CM and Loosereewanich, P and Perrault, G}, title = {Retention of asbestos fibres in lungs of workers with asbestosis, asbestosis and lung cancer, and mesothelioma in Asbestos township.}, journal = {Occupational and environmental medicine}, volume = {53}, number = {12}, pages = {801-807}, pmid = {8994398}, issn = {1351-0711}, mesh = {Adult ; Aged ; Asbestos/*adverse effects/analysis ; Asbestosis/complications/*pathology ; Humans ; Lung Neoplasms/complications/*pathology ; Male ; Mesothelioma/*pathology ; Middle Aged ; Mineral Fibers/adverse effects/analysis ; *Occupational Exposure ; Smoking/adverse effects ; }, abstract = {OBJECTIVE: To conduct a mineralogical study on the particles retained in the necropsied lungs of a homogenous group of asbestos miners and millers from Asbestos township (and a local reference population) and to consider the hypothesis that there is a difference in size between fibres retained in the lungs of patients with asbestosis with and without lung cancer.

METHODS: Samples of lung tissue were obtained from 38 patients with asbestosis without lung cancer, 25 with asbestosis and lung cancer, and 12 with mesothelioma, from necropsied Quebec chrysotile miners and millers from Asbestos township. Fibre concentrations in the lungs of these patients were compared with those in tissue from necropsies carried out on a local reference population: men who had died of either accidental death or acute myocardial infarction between 1990 and 1992. 23 were born before 1940 and 26 after 1940.

RESULTS: Geometric mean (GM) concentrations were higher in cases than in the controls for chrysotile fibres 5 to 10 microns long in patients with asbestosis with or without lung cancer; for tremolite fibres 5 to 10 microns long in all patients; for crocidolite, talc, or anthophyllite fibres 5 to 10 microns long in patients with mesothelioma; for chrysotile and tremolite fibres > or = 10 microns long in patients with asbestosis; and crocidolite, talc, or anthophyllite fibres > or = 10 microns long in patients with mesothelioma. However, median concentrations of each type of fibre in the lungs did not show any significant differences between the three disease groups. Average length to diameter ratios of the fibres were calculated to be larger in patients with asbestosis and lung cancer than in those without lung cancer for crocidolite fibres > or = 10 microns long, for chrysotile, amosite, and tremolite fibres 5 to 10 microns long, and for chrysotile and crocidolite fibres < 5 microns long. However, there was no statistical difference in the median length to diameter ratios for any type of fibres across the disease groups when they were calculated in each patient. Cumulative smoking index (pack-years) was higher in the group with asbestosis and lung cancer but was not statistically different from the two other disease groups.

CONCLUSION: Lung cancers occurred in workers with asbestosis from Asbestos township who had an equal concentration of retained fibres but a tendency to a higher length to diameter ratio of amphiboles. These workers had a 29% higher average cumulative smoking index.}, } @article {pmid8968079, year = {1996}, author = {Zanella, CL and Posada, J and Tritton, TR and Mossman, BT}, title = {Asbestos causes stimulation of the extracellular signal-regulated kinase 1 mitogen-activated protein kinase cascade after phosphorylation of the epidermal growth factor receptor.}, journal = {Cancer research}, volume = {56}, number = {23}, pages = {5334-5338}, pmid = {8968079}, issn = {0008-5472}, support = {R01 ES0006499/ES/NIEHS NIH HHS/United States ; R01 HL39 469/HL/NHLBI NIH HHS/United States ; T3207122//PHS HHS/United States ; }, mesh = {Animals ; Asbestos/*pharmacology ; Asbestos, Crocidolite/*pharmacology ; Calcium-Calmodulin-Dependent Protein Kinases/*metabolism ; Enzyme Activation/drug effects ; ErbB Receptors/*drug effects/metabolism ; Humans ; Insulin-Like Growth Factor I/pharmacology ; Mitogen-Activated Protein Kinase 1 ; Mitogen-Activated Protein Kinase 3 ; *Mitogen-Activated Protein Kinases ; Phosphorylation ; Platelet-Derived Growth Factor/pharmacology ; Pleura/*drug effects/metabolism ; Protein Processing, Post-Translational ; Rats ; Rats, Inbred F344 ; Signal Transduction/*drug effects ; }, abstract = {Asbestos fibers are human carcinogens with undefined mechanisms of action. In studies here, we examined signal transduction events induced by asbestos in target cells of mesothelioma and potential cell surface origins for these cascades. Asbestos fibers, but not their nonfibrous analogues, induced protracted phosphorylation of the mitogen-activated protein (MAP) kinases and extracellular signal-regulated kinases (ERK) 1 and 2, and increased kinase activity of ERK2. ERK1 and ERK2 phosphorylation and activity were initiated by addition of exogenous epidermal growth factor (EGF) and transforming growth factor-alpha, but not by isoforms of platelet-derived growth factor or insulin-like growth factor-1 in mesothelial cells. MAP kinase activation by asbestos was attenuated by suramin, which inhibits growth factor receptor interactions, or tyrphostin AG 1478, a specific inhibitor of EGF receptor tyrosine kinase activity (IC50 = 3 nM). Moreover, asbestos caused autophosphorylation of the EGF receptor, an event triggering the ERK cascade. These studies are the first to establish that a MAP kinase signal transduction pathway is initiated after phosphorylation of a peptide growth factor receptor following exposure to asbestos fibers.}, } @article {pmid8914714, year = {1996}, author = {Robinson, CF and Petersen, M and Sieber, WK and Palu, S and Halperin, WE}, title = {Mortality of Carpenters' Union members employed in the U.S. construction or wood products industries, 1987-1990.}, journal = {American journal of industrial medicine}, volume = {30}, number = {6}, pages = {674-694}, doi = {10.1002/(SICI)1097-0274(199612)30:6<674::AID-AJIM4>3.0.CO;2-R}, pmid = {8914714}, issn = {0271-3586}, mesh = {Accidental Falls/statistics & numerical data ; Age Factors ; Aged ; Asbestosis/mortality ; Black People ; Bone Neoplasms/mortality ; Breast Neoplasms, Male/mortality ; Cause of Death ; Construction Materials ; Female ; Humans ; Labor Unions ; Lung Diseases/mortality ; Lung Neoplasms/mortality ; Male ; Mesothelioma/mortality ; Nose Neoplasms/mortality ; Occupational Diseases/*mortality/prevention & control ; Occupational Exposure ; Proportional Hazards Models ; Pulmonary Emphysema/mortality ; Sex Factors ; Stomach Neoplasms/mortality ; Transportation ; United States/epidemiology ; White People ; Wood ; Wounds and Injuries/mortality/prevention & control ; Black or African American ; }, abstract = {This study evaluated the mortality of 27,362 members of the U.S. Carpenters' Union who died in 1987-1990. Age-adjusted proportionate mortality ratios (PMRs) and proportionate cancer mortality ratios (PCMRs) were computed using the U.S. age-, gender-, and race-specific proportional mortality for the years of the study. For white male carpenters who were last employed while in construction industry locals, raised mortality was observed for lung cancer (PCMR = 107, CI = 103, 111), bone cancer (PMR = 181, CI = 107, 286), asbestosis (PMR = 283, CI = 158, 457), emphysema (PMR = 115, CI = 102, 130), transportation injuries (PMR = 121, CI = 109, 135), and falls (PMR = 122, CI = 104, 142). For white male carpenters who were last employed while in industrial wood products locals, significantly raised mortality occurred for stomach cancer (PMR = 187, CI = 136, 250), male breast cancer (PCMR = 469, CI = 128, 720), and transportation injuries (PMR = 136, CI = 110, 173). Excess breast cancer was associated with last employment inn wood machining trades. Nasal cancer mortality was not elevated. A total of 121 mesotheliomas were observed. Contributing cause of death analyses revealed raised mortality for these and additional causes; 4,594 (18%) death certificates mentioned occupational and other lung disease as a contributing factor, resulting in significantly elevated mortality. These data show that construction carpenters have moderately elevated mortality for the diseases caused by asbestos (lung cancer and malignant mesothelioma) and from traumatic injuries. The finding of elevated mortality for stomach, bone, and breast cancer was unexpected and requires further evaluation of possible occupational factors. This study confirms that construction carpentry is an extremely hazardous trade. The data suggest that additional preventive action guarding against asbestos exposure and occupational injury is urgently needed in this occupation.}, } @article {pmid9409906, year = {1996}, author = {Schneider, J and Rödelsperger, K and Pohlabeln, H and Woitowitz, HJ}, title = {[Environmental and indoor air exposure to asbestos fiber dust as a risk and causal factor of diffuse malignant pleural mesothelioma].}, journal = {Zentralblatt fur Hygiene und Umweltmedizin = International journal of hygiene and environmental medicine}, volume = {199}, number = {1}, pages = {1-23}, pmid = {9409906}, issn = {0934-8859}, mesh = {Adult ; Aged ; Air Pollutants/*adverse effects ; Air Pollution, Indoor/*adverse effects ; Asbestos/*adverse effects ; Case-Control Studies ; Causality ; Child ; Female ; Germany/epidemiology ; Humans ; Male ; Mesothelioma/epidemiology/*etiology ; Middle Aged ; Odds Ratio ; Patient Care Team ; Pleural Neoplasms/epidemiology/*etiology ; Risk ; Risk Factors ; }, abstract = {In an interdisciplinary, multicentre case control study of the causal factors of the diffuse malignant mesothelioma (DMM) standardised histories where taken from n = 324 Patients suffering from DMM, n = 315 hospital control patients (KK) and n = 182 population controls (PK). For 66 DMM, 149 KK and 107 PK a risk from asbestos fibre dust at the workplace was not detectable. For latter persons indoor and outdoor asbestos exposure outside of the workplace were investigated. The following factors were examined: neighbourhood exposure from companies using asbestos, living in big cities and nearby main traffic roads, building materials containing asbestos, electric storage heaters and household contacts. For using electric storage heaters a statistically significant increased odds ratio (OR) was observed for DMM as well in comparison with KK (OR = 2.42; 95%-CI: 1.01-5.72) and in comparison for PK (OR = 2.91; 95%-CI: 1.08-7.80). Only outside of Hamburg an increased OR compared to KK was observed for people living in the neighbourhood of asbestos factories (OR = 16.3; 95%-CI: 1.35-196.8) and also, but only in Hamburg, compared to PK living nearby main traffic roads. There is only a trend for a mesothelioma-risk for household-contacts based on a few cases. In one DMM-patient without an occupational asbestos exposure the lung dust fibre analysis yielded 2.912 FB and 1.459 x 10(3) crocydolithe fibres per gram dried lung tissue. As a child he lived in the immediate vicinity of the blue asbestos mine in Wittenoom, Australia. Therefore in special cases a para-occupational asbestos or a neighbourhood asbestos exposure can be demonstrated as a risk factor of diffuse malignant mesothelioma.}, } @article {pmid9061058, year = {1996}, author = {Ascoli, V and Scalzo, CC and Facciolo, F and Martelli, M and Manente, L and Comba, P and Bruno, C and Nardi, F}, title = {Malignant mesothelioma in Rome, Italy 1980-1995. A retrospective study of 79 patients.}, journal = {Tumori}, volume = {82}, number = {6}, pages = {526-532}, doi = {10.1177/030089169608200603}, pmid = {9061058}, issn = {0300-8916}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos ; Biopsy, Needle ; Diagnosis, Differential ; Environmental Exposure ; Female ; Humans ; Male ; Mesothelioma/diagnosis/*epidemiology/*etiology ; Middle Aged ; Occupational Exposure ; Peritoneal Neoplasms/epidemiology ; Pleural Neoplasms/epidemiology ; Retrospective Studies ; Rome/epidemiology ; }, abstract = {AIM AND BACKGROUND: To evaluate the characteristics of a case-series of 79 malignant mesothelioma patients collected from the main teaching hospital of Rome, Italy, and other local clinics of Latium Region and to assess the role of asbestos exposure, since previous studies on the occurrence of the disease in this area were lacking.

METHODS: The study included cytohistologically diagnosed malignant mesothelioma (71 pleural, 7 peritoneal, and 1 testicular tunica vaginalis) detected or referred for consultation during the period 1980-1995. Information regarding occupational and/or nonoccupational exposures was derived from clinical records and interviews, when available.

RESULTS: Patients were resident in Rome and other towns of Latium; a few were from other parts of central and southern Italy. Exposure to asbestos was assessed for 45.5% of patients, another 45.5% had unknown exposure, and for the remaining 9% such information was lacking. Occupational exposure occurred in 53% of men for whom information was available and nonoccupational exposure occurred in 20% of women. The study identified two clusters of cases from an asbestos-cement plant and a facility where asbestos was ubiquitous. Furthermore, most exposed subjects reported occupations in the construction industry, which is particularly active in the Latium Region; others were railroad workers, naval mechanics and navy personnel, bakers, explosive workers and car mechanics. A few patients reported indoor exposure to asbestos at home and/or in the workplace.

CONCLUSIONS: The study confirmed that mesothelioma risk is present in several job titles of the construction industry, and it is no longer confined to workers employed in the manufacture or application of asbestos products. The occurrence of malignant mesothelioma in patients with unexpected occupational and nonoccupational exposures indicates the need for further investigation on previously underestimated exposures.}, } @article {pmid8968073, year = {1996}, author = {Chen, Q and Marsh, J and Ames, B and Mossman, B}, title = {Detection of 8-oxo-2'-deoxyguanosine, a marker of oxidative DNA damage, in culture medium from human mesothelial cells exposed to crocidolite asbestos.}, journal = {Carcinogenesis}, volume = {17}, number = {11}, pages = {2525-2527}, doi = {10.1093/carcin/17.11.2525}, pmid = {8968073}, issn = {0143-3334}, support = {ES01896/ES/NIEHS NIH HHS/United States ; ES06499/ES/NIEHS NIH HHS/United States ; ES06667/ES/NIEHS NIH HHS/United States ; }, mesh = {8-Hydroxy-2'-Deoxyguanosine ; Asbestos, Crocidolite/*toxicity ; Biomarkers/analysis ; Carcinogens/*toxicity ; Cell Line ; Culture Media ; *DNA Damage ; Deoxyguanosine/*analogs & derivatives/analysis ; Epithelium/chemistry/drug effects ; Guanine/analogs & derivatives/analysis ; Guanosine/analogs & derivatives/analysis ; Humans ; Oxidation-Reduction ; Pleura/*chemistry/*drug effects ; }, abstract = {Crocidolite asbestos is associated with the development of mesothelioma. Although chromosomal changes have been documented in mesothelial cells, the mechanisms of interaction of crocidolite with DNA remain obscure. Since human mesothelial cells are exquisitely sensitive to asbestos, oxidative DNA damage was measured in an asbestos-exposed human mesothelial cell line (MET5A) by assaying oxidized guanine bases [8-oxo-2'-deoxyguanosine (oxo8dG), 8-oxoguanine (oxo8G), and 8-oxoguanosine (oxo8Gua)] excreted into the spent culture medium after DNA repair or turnover. At growth inhibitory, but not cytolytic concentrations, asbestos caused significant elevation of all bases in the spent medium over a 48-h period. In contrast, riebeckite, a chemically similar, nonfibrous analog of crocidolite did not cause increased adduct release. Results show that oxidative RNA and DNA bases are produced in response to asbestos in target cells of asbestos-induced cancers.}, } @article {pmid8944725, year = {1996}, author = {Hamilton, RF and Iyer, LL and Holian, A}, title = {Asbestos induces apoptosis in human alveolar macrophages.}, journal = {The American journal of physiology}, volume = {271}, number = {5 Pt 1}, pages = {L813-9}, doi = {10.1152/ajplung.1996.271.5.L813}, pmid = {8944725}, issn = {0002-9513}, support = {HL-04804/HL/NHLBI NIH HHS/United States ; M01-RR-02558/RR/NCRR NIH HHS/United States ; }, mesh = {Apoptosis/*drug effects ; Asbestos, Crocidolite/*toxicity ; Asbestos, Serpentine/*toxicity ; Bronchoalveolar Lavage Fluid/cytology ; Calcium Compounds/toxicity ; Cell Survival/drug effects ; DNA/drug effects ; Humans ; Inflammation ; Macrophages, Alveolar/drug effects/pathology/*physiology ; Reference Values ; Silicates/toxicity ; }, abstract = {Asbestos refers to a group of fibrous minerals implicated in the development of several lung diseases, including fibrosis (asbestosis), cancer, and malignant mesothelioma. Although major health risks exist in occupationally exposed individuals, low-level exposures of asbestos may still contribute to health problems. The mechanism by which asbestos causes lung disease is not clearly understood but has been proposed to involve the alveolar macrophage (AM). We propose that asbestos induces apoptosis of AM, resulting in the development of an inflammatory state. In this study, we examined two forms of asbestos, chrysotile (CHR) and crocidolite (CRO), along with a control fiber, wollastonite (WOL), to characterize their relative cytotoxicity and ability to stimulate apoptosis in vitro. AM were cultured for 24 h with these particulates and examined for cell viability (trypan blue exclusion) and apoptosis (morphology, levels of cytosolic oligonucleosomal DNA fragments, and DNA ladder). In the absence of a decrease in cell viability, both CHR and CRO produced changes in cell morphology consistent with apoptosis. In addition, levels of cytoplasmic oligonucleosomal DNA (Cell Death Detection enzyme-linked immunosorbent assay) were significantly enhanced for CHR (3-25 micrograms/ml) and CRO (25-75 micrograms/ml) in a dose-dependent manner (a process that was inhibitable by 10 microM Z-Val-Ala-Asp fluoromethyl ketone, an interleukin-converting enzyme inhibitor). In contrast, WOL (up to 400 micrograms/ml) produced no significant DNA fragmentation in a 24-h culture. Neither CHR nor CRO caused DNA ladder formation in 24-h cell cultures. However, in 48-h cell cultures, both CHR- and CRO-exposed cells, but not WOL, resulted in the formation of DNA ladders characteristic of apoptosis. In summary, these results suggest that, unlike nonfibrogenic particulates, low doses of asbestos fibers cause apoptosis in cultured human AM that may be an early step in the development of lung fibrosis.}, } @article {pmid8944724, year = {1996}, author = {Ferriola, PC and Stewart, W}, title = {Fibronectin expression and organization in mesothelial and mesothelioma cells.}, journal = {The American journal of physiology}, volume = {271}, number = {5 Pt 1}, pages = {L804-12}, doi = {10.1152/ajplung.1996.271.5.L804}, pmid = {8944724}, issn = {0002-9513}, mesh = {Actins/analysis/ultrastructure ; Animals ; Asbestos ; Cell Line ; Cells, Cultured ; Epithelial Cells ; Epithelium/metabolism ; Fibronectins/analysis/*biosynthesis ; Gene Expression ; Mesothelioma/*metabolism/pathology ; Microscopy, Confocal ; Peritoneal Neoplasms/*metabolism/pathology ; *Pleura ; Rats ; Rats, Inbred F344 ; Tumor Cells, Cultured ; }, abstract = {Mesothelial cells are believed to be the progenitor cells for malignant mesothelioma, a tumor associated with exposure to asbestos and other mineral fibers. Little is known regarding fibronectin (Fn) function in mesothelial and mesothelioma cells. Fn RNA, protein levels, and localization were assessed in secondary cultures and later passages of spontaneously immortalized rat pleural mesothelial (NRM) cells and in neoplastic cell lines derived from asbestos-induced mesotheliomas. NRM cells expressed similar levels of Fn RNA regardless of passage number or cell density, as determined by Northern blotting and ribonuclease protection assays. Western blotting showed that Fn protein was both secreted by NRM cells and associated with cell lysates. Immunofluorescent confocal laser scanning microscopy demonstrated that secondary cultures of NRM cells assembled Fn into abundant homogeneous fibrillar arrays organized primarily between cells, whereas later passages of NRM cells displayed abundant but less homogeneous Fn organization. Fn RNA and protein levels in neoplastic mesothelial cells were slightly less or similar to levels in NRM cells. Organization of Fn in neoplastic cells was heterogeneous compared with secondary cultures of NRM cells, but Fn fibril formation was still apparent. F-actin microfilaments were organized in both NRM and neoplastic cells; however, actin stress fibers were maintained in neoplastic cells, whereas NRM cells displayed dense actin peripheral bands at high density. The maintenance of organized Fn and actin in mesothelioma cells is surprising and may contribute to the localized growth and invasive properties of these tumors.}, } @article {pmid8909614, year = {1996}, author = {Greenberg, M}, title = {Malignant mesothelioma in paper mill workers: where might the asbestos have come from?.}, journal = {American journal of industrial medicine}, volume = {30}, number = {5}, pages = {641}, doi = {10.1002/(SICI)1097-0274(199611)30:5<641::AID-AJIM13>3.0.CO;2-3}, pmid = {8909614}, issn = {0271-3586}, mesh = {Asbestos/*adverse effects ; Humans ; Mesothelioma/*epidemiology ; *Paper ; }, } @article {pmid8909610, year = {1996}, author = {Finkelstein, MM}, title = {Asbestos-associated cancers in the Ontario refinery and petrochemical sector.}, journal = {American journal of industrial medicine}, volume = {30}, number = {5}, pages = {610-615}, doi = {10.1002/(SICI)1097-0274(199611)30:5<610::AID-AJIM9>3.0.CO;2-W}, pmid = {8909610}, issn = {0271-3586}, mesh = {Aged ; Asbestos/*adverse effects ; Humans ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; Middle Aged ; Occupational Diseases/*mortality ; Occupations ; Odds Ratio ; Ontario/epidemiology ; Petroleum ; Retrospective Studies ; Risk Factors ; Smoking/adverse effects ; }, abstract = {Asbestos has been widely used in the refinery and petrochemical sector. Mesothelioma has occurred among maintenance employees, and it was hypothesized that mesothelioma is a marker for exposures which might increase lung cancer risk. A death certificate-based case-control study of mesothelioma and lung cancer from 1980 to 1992 was conducted in an Ontario county with a substantial presence of these industries. Each of the 17 men who died of mesothelioma and 424 with lung cancer were matched with controls who died of other causes. The Job and Industry fields on the death certificates were abstracted. Employment as a maintenance worker in the refinery and petrochemical sector was associated with an increased risk of mesothelioma (odds ratio: 24.5; 90% confidence interval 3.1-102). The risk of lung cancer among petrochemical workers, in comparison with all other workers in the county, was 0.88. In an internal comparison of maintenance employees with other blue-collar workers in the refinery and petrochemical sector, the odds ratio for lung cancer was 1.73 (90% confidence interval 0.83-3.6). This finding is consistent with no difference in risk between maintenance and other employees, but it is also compatible with study power being too low to achieve statistical significance. The hypothesis of increased lung cancer risk could be examined more fully with nested case-control studies in existing cohorts. Meanwhile, it would be prudent to reinforce adherence to asbestos control measures in the refinery and petrochemical sector.}, } @article {pmid8909601, year = {1996}, author = {Kohyama, N and Shinohara, Y and Suzuki, Y}, title = {Mineral phases and some reexamined characteristics of the International Union Against Cancer standard asbestos samples.}, journal = {American journal of industrial medicine}, volume = {30}, number = {5}, pages = {515-528}, doi = {10.1002/(SICI)1097-0274(199611)30:5<515::AID-AJIM1>3.0.CO;2-S}, pmid = {8909601}, issn = {0271-3586}, mesh = {Asbestos, Amosite/adverse effects/*chemistry ; Asbestos, Amphibole/adverse effects/*chemistry ; Asbestos, Crocidolite/adverse effects/*chemistry ; Asbestos, Serpentine/adverse effects/*chemistry ; Canada ; Carcinogens/analysis ; Differential Thermal Analysis ; Humans ; Lung Neoplasms/prevention & control ; Mesothelioma/prevention & control ; Microscopy, Electron ; Mineral Fibers/analysis ; Occupational Diseases/prevention & control ; Reference Standards ; X-Ray Diffraction ; Zimbabwe ; }, abstract = {Standard asbestos samples to be used for biomedical research were first prepared by the International Union Against Cancer (UICC) in 1966 in the United Kingdom and South Africa. Using modern techniques, X-ray diffractometry, analytical transmission electron microscopy, and thermal analysis, we have now analyzed these UICC samples to determine the mineral compositions (mineral phases) and their respective quantities. UICC chrysotile A (from Zimbabwe) contains 2% fibrous anthophyllite as impurity; chrysotile B (from Canada) does not contain any fibrous impurities, only non-fibrous minerals. UICC amosite and crocidolite are almost pure. UICC anthophyllite has 20-30% talc as impurity. The chemical compositions and fiber size distributions of the UICC asbestos samples have also been determined. The mean widths of the fibers of chrysotile A and B are smaller than those of the amphibole fibers. This agrees well with the earlier results which showed the two chrysotile samples to have a larger respirable fraction than the amphiboles.}, } @article {pmid8903324, year = {1996}, author = {Broaddus, VC and Yang, L and Scavo, LM and Ernst, JD and Boylan, AM}, title = {Asbestos induces apoptosis of human and rabbit pleural mesothelial cells via reactive oxygen species.}, journal = {The Journal of clinical investigation}, volume = {98}, number = {9}, pages = {2050-2059}, pmid = {8903324}, issn = {0021-9738}, support = {KO8 ES00253/ES/NIEHS NIH HHS/United States ; PPG HL24075/HL/NHLBI NIH HHS/United States ; R01 ESO6331/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Annexin A5/metabolism ; *Apoptosis ; Asbestos/*toxicity ; Catalase/metabolism ; Cell Division/drug effects ; Cells, Cultured ; Chelating Agents/chemistry ; DNA Fragmentation ; Deferoxamine/chemistry ; Enzyme Inhibitors/pharmacology ; Epithelial Cells ; Epithelium/*drug effects ; Humans ; Hypoxia/physiopathology ; Pleura/cytology/*drug effects ; Poly(ADP-ribose) Polymerase Inhibitors ; Protein Binding ; Rabbits ; *Reactive Oxygen Species ; Superoxide Dismutase/metabolism ; }, abstract = {Mesothelial cells, the progenitor cell of the asbestos-induced tumor mesothelioma, are particularly sensitive to the toxic effects of asbestos, although the molecular mechanisms by which asbestos induces injury in mesothelial cells are not known. We asked whether asbestos induced apoptosis in mesothelial cells and whether reactive oxygen species were important. Pleural mesothelial cells (rabbit or human) were exposed to asbestos (crocidolite, amosite, or chrysotile) or control particles at moderate doses (1-10 microg/cm2) over 24 h and evaluated for oligonucleosomal DNA fragmentation, loss of membrane phospholipid asymmetry, and nuclear condensation. Asbestos fibers, not control particles, induced apoptosis in mesothelial cells by all assays and induction of apoptosis was dose dependent for all types of asbestos, with crocidolite (5 microg/cm2) inducing 15.0+/-1.1% (mean+/-SE; n = 12) apoptosis versus control particles < 4%. Apoptosis induced by asbestos, but not by actinomycin D, was inhibited by extracellular catalase, superoxide dismutase in the presence of catalase, hypoxia (8% oxygen), deferoxamine, 3-aminobenzamide [an inhibitor of poly(ADP-ribosyl) polymerase], and cytochalasin B. Only catalase and cytochalasin B decreased fiber uptake. We conclude that asbestos induces apoptosis in mesothelial cells via reactive oxygen species. Escape from this pathway could allow the abnormal survival of mesothelial cells with asbestos-induced mutations.}, } @article {pmid9001057, year = {1996}, author = {Burrus, O}, title = {[A known nuisance, recognized again ... asbestos].}, journal = {Revue de l'infirmiere}, volume = {}, number = {15-16}, pages = {58-65}, pmid = {9001057}, issn = {1293-8505}, mesh = {Asbestos/*adverse effects ; Humans ; Mesothelioma/chemically induced/prevention & control ; *Occupational Exposure ; Occupational Health Nursing/legislation & jurisprudence ; }, } @article {pmid8940843, year = {1996}, author = {Tanaka, H and Iuchi, K and Nanjou, S and Ikeda, M and Takana, Y and Mori, T}, title = {[Two cases of recurrent hydropneumothorax caused by malignant pleural mesothelioma].}, journal = {[Zasshi] [Journal]. Nihon Kyobu Geka Gakkai}, volume = {44}, number = {10}, pages = {1877-1881}, pmid = {8940843}, issn = {0369-4739}, mesh = {Aged ; Humans ; Hydropneumothorax/diagnosis/*etiology ; Male ; Mesothelioma/*complications ; Pleural Neoplasms/*complications ; Recurrence ; }, abstract = {We reported and reviewed 8 cases including two authors' cases in the Japanese literature, the incidence of pneumothorax associated with primary pulmonary neoplasms was less than 0.05%, however, in the case of malignant pleural mesothelioma, was as high as 10.36%. Mean age of patients was 67 year-old and recurrent hydropneumothorax was characterized in the clinical course. For the elderly with hydropneumothorax, it was necessary to rule out the malignant mesothelioma based on the past history of asbestos exposure, analysis of value of hyaluronic acid in the pleural effusion and the CT scan findings revealing pleural thickening, plaques and nodules. Only two out of 8 cases, were possible to undergo curative resection. Two authors' cases had undergone pleura resection and pathological findings indicated epithelial type of malignant mesothelioma. One died in 3 years and the other has been alive for one and half year since the operation.}, } @article {pmid9036830, year = {1996}, author = {Catania, V and Bonaccorso, R and Fraggetta, F and Vecchio, S and Grasso, F and Cammisuli, F and Minutolo, V and Cavallaro, V}, title = {[Peritoneal mesothelioma. A case report].}, journal = {Annali italiani di chirurgia}, volume = {67}, number = {5}, pages = {697-701}, pmid = {9036830}, issn = {0003-469X}, mesh = {Antibiotics, Antineoplastic/administration & dosage ; Antineoplastic Agents/administration & dosage ; Cisplatin/administration & dosage ; Follow-Up Studies ; Humans ; Injections, Intraperitoneal ; Injections, Intravenous ; Male ; Mesothelioma/diagnosis/mortality/*therapy ; Middle Aged ; Mitomycin/administration & dosage ; Peritoneal Neoplasms/diagnosis/mortality/*therapy ; Time Factors ; }, abstract = {Peritoneal mesothelioma is a rare neoplasm (annual incidence: 1-2 cases per million in the general population) and forms about 10% of all mesotheliomas. The authors report a case of malignant mesothelioma of the peritoneum in a male, 61 years old. After laparotomy the patient was treated with intraperitoneal administration of cisplatin (40 mg/m2 day 1-2-3-29-30-31) and intravenous administration of mitomycin C (10 mg/m2 day 1). The renal toxicity was avoided with the GSH and with prehydration before and after administration of the cisplatin. The bone marrow toxicity was avoided with the subcutaneous administration of G-CSF (300 mg three times each week) and erythropoietin (10.000 U three times a week). After the first cycle, with the reduction of the ascites, the cisplatin was administered intravenously too. After six cycles of chemotherapy (18 months after laparotomy) the patient is alive and he has a performance status of 1 (ECOG/WHO). The chemotherapy with cisplatin and mitomycin C must be preferred to the anthracycline in all the patient with cardiologic involvement. The cisplatin administered by intracavitary route give a quick response with less systemic toxicity. A review of the literature confirms the rarity of this pathology, linked epidemiologically with exposure to asbestos, and the difficulty of the preoperative diagnosis: in fact cytologic assay and ultrasonographic and TC scan always don't permit to discover a mesothelioma. The laparotomy and the laparoscopy are useful in the P.M. for the possibility of the biopsies and the apposition of the catheters for intracavitary therapy. The response of peritoneal mesothelioma to treatment is poor. The median survival after the appearance of the symptom is less than 18 months.}, } @article {pmid8944121, year = {1996}, author = {Lewin, M and Arrivé, L and Wendum, D and Monnier-Cholley, L and Bouttier, E and Tubiana, JM}, title = {[Imaging of peritoneal mesotheliomas].}, journal = {Journal de radiologie}, volume = {77}, number = {9}, pages = {649-656}, pmid = {8944121}, issn = {0221-0363}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Mesothelioma/diagnosis/*diagnostic imaging ; Middle Aged ; Peritoneal Neoplasms/diagnosis/*diagnostic imaging ; Retrospective Studies ; *Tomography, X-Ray Computed ; Ultrasonography ; }, abstract = {Peritoneal mesothelioma is a rare, either benign or malignant tumor of the peritoneum. We retrospectively analyzed the imaging features of six malignant and three benign peritoneal mesothelioma. Asbestos exposure was proven in three of the six malignant cases and in none of the three benign cases. Ascites was found in seven patients (78%), peritoneal masses in eight patients (88%), small peritoneal nodules in six patients (66%), parietal peritoneal thickening in six patients (66%), thickened mesentery in five patients (55%) and pleural plaques as well as nodules in one patient. These imaging features support the diagnosis of peritoneal mesothelioma but do not allow differentiation between benign and malignant forms of peritoneal mesothelioma.}, } @article {pmid8917414, year = {1996}, author = {Alderisio, M and Giovagnoli, MR and Cenci, M and Vecchione, A}, title = {Asbestos bodies in the sputum of workers exposed to environmental pollution.}, journal = {Anticancer research}, volume = {16}, number = {5A}, pages = {2965-2968}, pmid = {8917414}, issn = {0250-7005}, mesh = {Adult ; Aged ; Aged, 80 and over ; Air Pollutants/*analysis ; Air Pollutants, Occupational/*analysis ; Asbestos/*isolation & purification ; Humans ; Lung/pathology ; Metaplasia ; Middle Aged ; Occupations ; Smoking/adverse effects ; *Sputum/cytology ; }, abstract = {The diseases related to asbestos exposure (pulmonary fibrosis, broncogenic carcinoma and mesothelioma) are of widespread interest and involve different socio-economic groups of subjects. Since these pathologies have a wide diffusion in the industrial world, we carried out an investigation on two populations occupationally exposed to air pollution and asbestos fibre inhalation (164 traffic policemen of the municipal district of Rome and 218 railwaymen) and on a control group (119 residents in a rural district of Perugia) for the detection of asbestos bodies in the sputum. The results obtained from traffic policemen and railwaymen workers differred significantly from those of the control group. The presence of asbestos bodies in traffic policemen seems to be determined by a strong synergetic effect between gaseous urban pollution, cigarette smoking habits and asbestos dust arising from car brakes and building materials, whereas, in railwaymen it seems to be more directly correlated to exposure.}, } @article {pmid8880114, year = {1996}, author = {McDonald, JC and McDonald, AD}, title = {The epidemiology of mesothelioma in historical context.}, journal = {The European respiratory journal}, volume = {9}, number = {9}, pages = {1932-1942}, doi = {10.1183/09031936.96.09091932}, pmid = {8880114}, issn = {0903-1936}, mesh = {Asbestos/adverse effects/analysis ; Asbestos, Amosite/adverse effects/analysis ; Asbestos, Amphibole/adverse effects/analysis ; Asbestos, Crocidolite/adverse effects/analysis ; Asbestos, Serpentine/adverse effects/analysis ; Carcinogens/adverse effects/analysis ; Case-Control Studies ; Cohort Studies ; Female ; History, 20th Century ; Humans ; Lung Neoplasms/*epidemiology/etiology/history ; Male ; Mesothelioma/*epidemiology/etiology/history ; Mineral Fibers/adverse effects/analysis ; Mining ; Occupational Diseases/epidemiology/etiology/history ; Reproducibility of Results ; Risk Factors ; }, abstract = {Primary malignant mesothelial tumours were recognized by pathologists before asbestiform minerals (chrysotile, crocidolite and amosite) were mined commercially. The discovery, 40 yrs ago, of a causal link with crocidolite and the wide-ranging epidemiological studies which followed are the subject of this review. Early case-control and descriptive surveys, supplemented by cohort studies in insulation workers and chrysotile miners, quickly demonstrated major occupational and geographical differences, with high risk in naval dockyard areas and in the heating trades. In the 1980s, reliable cohort surveys showed that in mining and in the manufacture of asbestos products the mesothelioma risk was much higher when exposure included crocidolite or amosite than chrysotile alone. However, qualitative and quantitative information on exposure was too often inadequate for this evidence to be conclusive. Well-controlled lung fibre analyses have reduced these deficiencies and demonstrated the probable implications of the greater biopersistence of amphibole fibres. Chrysotile for industrial use often contains low concentrations of fibrous tremolite, which may well explain the few cases of mesothelioma associated with this type of asbestos. Progress in this field has been much retarded by controversy, for which the 20 year gap between the availability of reliable estimates of risk for the mining of chrysotile and that for crocidolite or amosite may have been largely responsible.}, } @article {pmid8876792, year = {1996}, author = {Smith, AH and Wright, CC}, title = {Chrysotile asbestos is the main cause of pleural mesothelioma.}, journal = {American journal of industrial medicine}, volume = {30}, number = {3}, pages = {252-266}, doi = {10.1002/(SICI)1097-0274(199609)30:3<252::AID-AJIM2>3.0.CO;2-0}, pmid = {8876792}, issn = {0271-3586}, support = {ESO189/ES/NIEHS NIH HHS/United States ; }, mesh = {Air Pollutants, Occupational/*adverse effects/analysis ; Animals ; Asbestos, Amphibole/administration & dosage/adverse effects/analysis ; Asbestos, Serpentine/administration & dosage/*adverse effects/analysis ; Canada/epidemiology ; Cohort Studies ; Disease Models, Animal ; Follow-Up Studies ; Humans ; Lung Neoplasms/epidemiology/*etiology ; Mesothelioma/epidemiology/*etiology ; Meta-Analysis as Topic ; Occupational Diseases/epidemiology/*etiology ; Occupational Exposure/adverse effects ; Rodentia ; United States/epidemiology ; }, abstract = {In contrast to amphibole forms of asbestos, chrysotile asbestos is often claimed to be only a minor cause of malignant pleural mesothelioma, a highly fatal cancer of the lining of the thoracic cavity. In this article we examine the evidence from animal and human studies that relates to this issue. Reported data do not support widely quoted views regarding the relative inertness of chrysotile fibers in mesothelioma causation. In fact, examination of all pertinent studies makes it clear that chrysotile asbestos is similar in potency to amphibole asbestos. Since asbestos is the major cause of mesothelioma, and chrysotile constitutes 95% of all asbestos use world wide, it can be concluded that chrysotile asbestos is the main cause of pleural mesothelioma in humans.}, } @article {pmid8764743, year = {1996}, author = {Clement, PB and Young, RH and Scully, RE}, title = {Malignant mesotheliomas presenting as ovarian masses. A report of nine cases, including two primary ovarian mesotheliomas.}, journal = {The American journal of surgical pathology}, volume = {20}, number = {9}, pages = {1067-1080}, doi = {10.1097/00000478-199609000-00004}, pmid = {8764743}, issn = {0147-5185}, mesh = {Adolescent ; Adult ; Female ; Humans ; Immunohistochemistry ; Mesothelioma/chemistry/*pathology/secondary ; Middle Aged ; Ovarian Neoplasms/chemistry/*pathology/secondary ; Peritoneal Neoplasms/pathology ; Prognosis ; }, abstract = {Nine cases of malignant mesothelioma (MM) presenting as ovarian masses occurred in female patients aged 16 to 63 (median, 52) years. In most of the cases, the referring pathologist initially misdiagnosed the neoplasm or was uncertain about its nature. In two cases, the tumors were confined to one or both ovaries, representing primary ovarian MMs; only one similar case has been previously reported. In the other cases, widespread peritoneal tumor precluded definite conclusions about the primary or secondary nature of the ovarian involvement. That at least some of the latter were also primary ovarian MMs is suggested by a degree of ovarian enlargement, the striking parenchymal replacement, or both, which are not usually seen in cases of secondary ovarian involvement by peritoneal MMs. The clinical presentation was usually that of abdominal or pelvic pain or abdominal swelling, an adnexal mass on pelvic examination or at laparotomy, or combinations thereof. One tumor was an autopsy finding. There was no history of asbestos exposure in any patient. Eight patients underwent bilateral oophorectomy, usually with hysterectomy and biopsies of extraovarian tumor. Four patients were given chemotherapy and one, radiation therapy. Follow-up in five cases revealed that three patients had died of tumor at postoperative intervals of 8 to 44 months, one was alive with persistent tumor at 18 months, and one was alive with no clinical evidence of tumor at 11 years. The ovaries were replaced by tumors 3 to 15 cm in maximum diameter; seven were bilateral. The neoplastic tissue was typically solid, but small cysts were present in two cases, and one tumor was a unilocular cyst with a solid mural nodule. On microscopic examination, tumor involved both the serosa and the parenchyma of the ovary in seven cases, the serosa only in one case, and the parenchyma only in one case. Seven tumors were exclusively epithelial, with papillary, tubular-glandular, and solid patterns, and two were biphasic. The cells in the epithelial mesotheliomas usually exhibited moderate atypicality and a low mitotic rate. The stroma was typically hyalinized, and in three of the cases with a papillary pattern papillae with hyalinized cores were a striking finding. Psammoma bodies were present in three cases. Histochemical and immunohistochemical stains confirmed the mesothelial nature of the tumor cells. Because of the wide variety of microscopic patterns in MMs, the differential diagnosis of ovarian MM includes a variety of primary and metastatic ovarian tumors as well as other peritoneal mesothelial lesions.}, } @article {pmid8765152, year = {1996}, author = {Rüegger, M}, title = {[Are artificial mineral fibers harmful to health and unsuitable for asbestos substitute?].}, journal = {Praxis}, volume = {85}, number = {33}, pages = {961-966}, pmid = {8765152}, issn = {1661-8157}, mesh = {Animals ; Asbestos/*adverse effects ; *Carcinogens ; Glass ; Humans ; Lung/metabolism ; Microscopy, Electron, Scanning ; Mineral Fibers/*adverse effects ; Neoplasms/etiology ; Neoplasms, Experimental/etiology ; Particle Size ; Rodentia ; }, abstract = {The increasing knowledge about the carcinogenic properties of asbestos have given rise to an extensive research on possible adverse health effects of alternative materials. Especially man-made mineral fibers (MMMF), i.e. glass fibers, but also glass-, stone- and slag wools turned out to be of unique interest, because they have already been used for several decades for isolation purposes. It is generally accepted that the carcinogenic potential of any fiber is related to its dimension and its biopersistence. Based on series of experiments, it could be demonstrated that only fibers longer than 5 microns, thinner than 3 microns and with a length/diameter ratio of more than 3 are able to reach the periphery of the lung. Excepting the refractory (ceramic) fibers, studies showed that inhalation did not provoke tumors in rodents, whereas the intratracheal, intrapleural and intraperitoneal instillation induced a carcinogenic effect for most kinds of MMMF. Compared to asbestos, MMMF clears out much faster from the lung tissue. Finally, there is no consistent epidemiological evidence for an increased standardized mortality ratio due to malignant tumors of the airways and malignant mesotheliomas in individuals formerly exposed to MMMF. Out of the rather theoretical tumor risk, there is a far more common and itchy skin problem to mention, namely glass-fiber dermatitis, which appears when one is handling without protection thicker and therefore more stinging fibers. In the light of these facts and based on the actual exposure situation, there is no clearcut cancer risk, when one is handling glass fibers and wool; however, the potential risk of exposure to refractory ceramic fibers has to be evaluated with more caution.}, } @article {pmid8983466, year = {1996}, author = {Edward, AT and Whitaker, D and Browne, K and Pooley, FD and Gibbs, AR}, title = {Mesothelioma in a community in the north of England.}, journal = {Occupational and environmental medicine}, volume = {53}, number = {8}, pages = {547-552}, pmid = {8983466}, issn = {1351-0711}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos, Amphibole/*adverse effects ; Body Burden ; England/epidemiology ; Female ; Humans ; Lung/chemistry ; Lung Neoplasms/*epidemiology/etiology ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Exposure/*adverse effects ; }, abstract = {OBJECTIVES: To find the numbers of mesotheliomas in Calderdale over the period 1966-94 and determine their relation to asbestos exposure, pathology, and mineral fibre burden within the lungs of affected subjects.

METHODS: Cases were entered into the study if the subject has been diagnosed with mesothelioma after postmortem and histopathological examinations. Occupational data were obtained mainly from the case records of the Cape Asbestos medical officer, hospital, and medical practitioner and from death certificates. Analyses of the mineral fibres were performed with transmission electron microscopy and energy dispersive x ray spectrometry.

RESULTS: 73 mesotheliomas were diagnosed from 1966 to 1994. Forty four were associated with exposure at the Acre Mill factory, which manufactured asbestos products. Concentrations of amphibole asbestos fibres were found to be raised above controls in 31 out of 32 cases associated with Acre Mill exposure, in 10 out of 12 other cases exposed to asbestos and eight out of 17 cases not exposed to asbestos.

CONCLUSIONS: There was a high number of mesotheliomas in Calderdale. More than half of the cases were associated with occupation at the Acre Mill factory and were associated with exposure to amphibole asbestos, predominantly crocidolite. No cases associated with neighbourhood exposure to asbestos were identified.}, } @article {pmid8837340, year = {1996}, author = {Eyden, BP and Banik, S and Harris, M}, title = {Malignant epithelial mesothelioma of the peritoneum: observations on a problem case.}, journal = {Ultrastructural pathology}, volume = {20}, number = {4}, pages = {337-344}, doi = {10.3109/01913129609016334}, pmid = {8837340}, issn = {0191-3123}, mesh = {Aged ; Biomarkers/analysis ; Carcinoma/pathology ; Diagnosis, Differential ; Fatal Outcome ; Humans ; Immunohistochemistry ; Male ; Mesothelioma/metabolism/*pathology/ultrastructure ; Microscopy, Electron ; Peritoneal Neoplasms/metabolism/*pathology/ultrastructure ; }, abstract = {A 71-year-old asbestos-exposed male with symptoms suggestive of asbestosis for the previous 8 years presented with abdominal distension and ascites. Clinically, a diagnosis of mesothelioma carcinoma was made. Light microscopy of an omental biopsy failed to advance the diagnosis: The tumor was a solid, papillary, and glandular neoplasm lacking mucin and hyaluronidase-sensitive Alcian blue staining material. Immunohistochemistry gave positive results for Ber-EP4, LeuM1, and CEA, markers, favoring carcinoma. Electron microscopy revealed processes in channels and lumina, which were long, slender, and uncoated with a length: diameter ratio of 19.7. A few possessed small rootlets. A glycocalyx and glycocalyceal bodies were not seen. Other features included tonofibrils, a basal lamina, and desmosomes. The patient died 3 months following the onset of abdominal symptoms. Autopsy findings included solid and papillary tumor throughout the peritoneum, but no intrinsic tumor of the gastrointestinal tract or elsewhere. Arriving at a final diagnosis was complicated by immunohistochemistry, which favored carcinoma, and ultrastructure, which suggested mesothelioma. Taking into account all lines of evidence, it was concluded that the tumor was probably a mesothelioma but one with some features developed to an extent more typical of carcinoma.}, } @article {pmid8683242, year = {1996}, author = {Weissmann, LB and Corson, JM and Neugut, AI and Antman, KH}, title = {Malignant mesothelioma following treatment for Hodgkin's disease.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {14}, number = {7}, pages = {2098-2100}, doi = {10.1200/JCO.1996.14.7.2098}, pmid = {8683242}, issn = {0732-183X}, mesh = {Adult ; Child ; Female ; Hodgkin Disease/*radiotherapy ; Humans ; Male ; Mesothelioma/*etiology ; *Neoplasms, Radiation-Induced ; Peritoneal Neoplasms/etiology ; Pleural Neoplasms/etiology ; Radiotherapy/adverse effects ; }, abstract = {PURPOSE: Asbestos exposure is the major known risk factor for mesothelioma, but several case reports have suggested a link between radiation therapy and subsequent development of malignant mesothelioma. This report explores a possible association between radiation therapy for Hodgkin's disease and mesothelioma.

PATIENTS AND METHODS: Four cases of malignant mesothelioma were observed following Hodgkin's disease at the Mesothelioma Clinic of the Dana-Farber Cancer Institute. A fifth such patient was found after a review of the literature.

RESULTS: In all five cases, the mesothelioma arose in the field of prior radiotherapy. No history of asbestos exposure was elicited by careful questioning or by review of chest radiographs. Examination of lung tissue in one patient showed 250 ferruginous bodies per gram of lung tissue, consistent with no significant prior exposure. The mean interval between radiation treatment for Hodgkin's disease and development of mesothelioma was 15 years, which emphasizes the need for continued follow-up and evaluation of these patients and supports a causal relationship.

CONCLUSION: Mesothelioma may need to be added to the list of second malignancies that arise following radiation therapy for Hodgkin's disease. Further support is given to a causal link between radiation exposure and mesothelioma.}, } @article {pmid8635157, year = {1996}, author = {Sarić, M and Curin, K}, title = {Malignant tumours of the gastrointestinal tract in an area with an asbestos-cement plant.}, journal = {Cancer letters}, volume = {103}, number = {2}, pages = {191-199}, doi = {10.1016/0304-3835(96)04214-0}, pmid = {8635157}, issn = {0304-3835}, mesh = {Age Factors ; Air Pollutants ; *Asbestos ; Croatia ; Environmental Pollutants ; Female ; Gastrointestinal Neoplasms/*epidemiology ; Humans ; *Industry ; Male ; }, abstract = {Data on persons who died of cancer of the gastrointestinal tract in a Croatian coastal area with an asbestos-cement plant were analysed for the period 1970-1990. By poll method applied to the families of deceased subjects, additional data on occupation, lifestyle, educational level, length of resistance and cancer mortality among relatives were collected. The investigation showed that in the study area, but also in certain narrower locations within it (subarea settlements), some of the tumours studied occurred at higher rates than expected. Although not conclusive, these findings may indicate a role of environmental exposure to asbestos, particularly in the occurrence of peritoneal mesothelioma.}, } @article {pmid8804939, year = {1996}, author = {Sakellariou, K and Malamou-Mitsi, V and Haritou, A and Koumpaniou, C and Stachouli, C and Dimoliatis, ID and Constantopoulos, SH}, title = {Malignant pleural mesothelioma from nonoccupational asbestos exposure in Metsovo (north-west Greece): slow end of an epidemic?.}, journal = {The European respiratory journal}, volume = {9}, number = {6}, pages = {1206-1210}, doi = {10.1183/09031936.96.09061206}, pmid = {8804939}, issn = {0903-1936}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Asbestos, Amphibole/adverse effects ; Chi-Square Distribution ; Environmental Exposure/*adverse effects ; Female ; Greece/epidemiology ; Humans ; Incidence ; Male ; *Mesothelioma/epidemiology/etiology ; Middle Aged ; *Pleural Neoplasms/epidemiology/etiology ; Risk Factors ; }, abstract = {Inhabitants of the Metsovo area, north-west Greece have been exposed since childhood to inhalation of asbestos, from a material containing tremolite, used for whitewashing ("luto soil"). This has resulted in endemic pleural calcifications (47% of adult population) and increased incidence of malignant pleural mesothelioma (MPM). In 1987, we reported that the incidence of MPM between 1981-1985 was around 300 times higher than expected in a nonasbestos exposed population (seven cases in 5 yrs in a population of 4,000-5,000). The present study is an updated report regarding this "mesothelioma epidemic", in conjunction with the diminished use and final abandonment of "luto soil" in the early 1980s. It appears that the incidence of MPM in Metsovo has dropped considerably since our first report. Between 1985-1994, we diagnosed six such cases (incidence rate = 1.4 cases per 10,000 person-years), whilst between 1980-1984 eight cases had been diagnosed (incidence rate = 3.7 cases per 10,000 person-years). Although, because of the small number of cases, this did not reach statistical significance (p = 0.08), we note that the incidence is now considerably lower than before. Had it remained unchanged, we would have expected 17 cases of MPM instead of six. This drop follows the diminished use of "luto" whitewash (by 92% of the population in 1950 and only 18% in 1980). If we take into account a 30-40 year latency period for mesothelioma, we expect that the "Metsovo mesothelioma epidemic" will fade away by the year 2020-2030, since the material has not been used since 1985.}, } @article {pmid8769502, year = {1996}, author = {Ferrer, JS and Muñoz, XG and Orriols, RM and Light, RW and Morell, FB}, title = {Evolution of idiopathic pleural effusion: a prospective, long-term follow-up study.}, journal = {Chest}, volume = {109}, number = {6}, pages = {1508-1513}, doi = {10.1378/chest.109.6.1508}, pmid = {8769502}, issn = {0012-3692}, mesh = {Aged ; Exudates and Transudates/chemistry ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Pleura/pathology ; *Pleural Effusion/diagnosis/etiology/metabolism/pathology ; Prospective Studies ; Recurrence ; }, abstract = {UNLABELLED: The management of idiopathic pleural effusion remains controversial. Because the long-term evolution of this entity is not well known, two different approaches, aggressive and conservative, have been proposed. We conducted a 10-year study of the evolution of idiopathic pleural effusion.

METHODS: Between 1984 and 1994, we prospectively studied 40 consecutive patients (30 men and 10 women; mean [+/- SD] age, 53.8 +/- 19.4 years) with exudative pleural effusion undiagnosed after exhaustive evaluation. The pleural fluid adenosine deaminase level was below 43 IU/L in all; periodic chest radiographs and clinical evaluation were carried out in all patients for a mean of 62 months (range, 36 to 108 months). Further diagnostic procedures were performed whenever the effusion recurred or when indicated by the clinical picture.

RESULTS: Effusions resolved in a mean time of 5.6 months (range, 7 days to 48 months). Five patients (12.5%) had one or more relapses of their pleural effusion, and in a further 5 (12.5%), the effusion persisted unchanged for more than 1 month. In 32 cases (80%), no potential cause of the effusion was detected. The diagnoses in the remaining eight cases were asbestos pleural effusion in three, pulmonary adenocarcinoma in one, mesothelioma in one, congestive heart failure in one, liver cirrhosis in one, and rheumatoid arthritis in one. Tuberculosis was not detected in any of the cases, although 19 patients initially had positive tuberculin tests.

CONCLUSIONS: Most idiopathic pleural effusions follow a benign course. Our results support conservative treatment of patients with idiopathic pleural effusion. Antituberculous treatment does not appear to he warranted, regardless of tuberculin test results, if the pleural fluid adenosine deaminase level is not elevated.}, } @article {pmid8691057, year = {1996}, author = {Mustacchi, P}, title = {Lung cancer latency and asbestos liability.}, journal = {The Journal of legal medicine}, volume = {17}, number = {2}, pages = {277-300}, doi = {10.1080/01947649609511008}, pmid = {8691057}, issn = {0194-7648}, mesh = {Adolescent ; Adult ; Aged ; Asbestosis/*complications ; Eligibility Determination/legislation & jurisprudence ; Female ; Humans ; *Liability, Legal ; Lung Neoplasms/*etiology ; Male ; Mesothelioma/*etiology ; Middle Aged ; Occupational Diseases/*etiology ; Risk Factors ; Smoking/adverse effects/legislation & jurisprudence ; Time Factors ; Workers' Compensation/legislation & jurisprudence ; }, } @article {pmid8897628, year = {1996}, author = {Miller, BH and Rosado-de-Christenson, ML and Mason, AC and Fleming, MV and White, CC and Krasna, MJ}, title = {From the archives of the AFIP. Malignant pleural mesothelioma: radiologic-pathologic correlation.}, journal = {Radiographics : a review publication of the Radiological Society of North America, Inc}, volume = {16}, number = {3}, pages = {613-644}, doi = {10.1148/radiographics.16.3.8897628}, pmid = {8897628}, issn = {0271-5333}, mesh = {Aged ; Humans ; Male ; Mesothelioma/*diagnostic imaging/*pathology/therapy ; Pleural Neoplasms/*diagnostic imaging/*pathology/therapy ; Tomography, X-Ray Computed ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare malignant neoplasm that typically affects individuals occupationally exposed to asbestos through a variety of industries. The patients experience an insidious onset of symptoms, including dyspnea, chest pain, cough, malaise, and weight loss. The pathologic diagnosis of MPM is difficult, and special stains or immunohistochemical or ultrastructural analysis may be required to differentiate MPM from metastatic adenocarcinoma. The tumor affects both the parietal and visceral pleural surfaces and progresses to encase the lung and invade the lung, mediastinum, and chest wall. Radiologically, MPM manifests as unilateral pleural effusion, pleural nodules, or pleural masses. Imaging studies are useful for diagnosis and staging in patients who are potential surgical candidates. Although a variety of multimodality therapies are available and radical surgical procedures have been developed, the prognosis remains dismal.}, } @article {pmid8858903, year = {1996}, author = {Merler, E and Ricci, P and Silvestri, S}, title = {Crocidolite and not chrysotile was mainly used by the Italian railroad system.}, journal = {La Medicina del lavoro}, volume = {87}, number = {3}, pages = {268-269}, pmid = {8858903}, issn = {0025-7818}, mesh = {Asbestos, Crocidolite/*adverse effects ; Asbestos, Serpentine/*adverse effects ; Humans ; Italy ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Occupational Diseases/etiology ; Occupational Exposure/*adverse effects ; *Railroads ; }, } @article {pmid8732655, year = {1996}, author = {Ascoli, V and Facciolo, F and Rahimi, S and Scalzo, CC and Nardi, F}, title = {Concomitant malignant mesothelioma of the pleura, peritoneum, and tunica vaginalis testis.}, journal = {Diagnostic cytopathology}, volume = {14}, number = {3}, pages = {243-248}, doi = {10.1002/(SICI)1097-0339(199604)14:3<243::AID-DC9>3.0.CO;2-I}, pmid = {8732655}, issn = {8755-1039}, mesh = {Asbestos/adverse effects ; Biopsy, Needle ; Humans ; Immunohistochemistry ; Keratins/analysis ; Male ; Mesothelioma/etiology ; Microscopy, Electron ; Middle Aged ; Neoplasms, Multiple Primary/*diagnosis ; Occupational Diseases/diagnosis/etiology ; Peritoneal Neoplasms/diagnosis/etiology ; Pleural Neoplasms/diagnosis/etiology ; Testicular Neoplasms/diagnosis/etiology ; Tomography, X-Ray Computed ; Vimentin/analysis ; }, abstract = {We describe the cytohistological, immunohistochemical and ultrastructural findings in a 55-yr-old-man with history of asbestos exposure and diffuse malignant mesothelioma (DMM) of the pleura, peritoneum, and tunica vaginalis presenting with chest pain and scrotal swelling. Pleural fine-needle aspiration (FNA) revealed mesenchymal elements and spindle-shaped epithelial-like cells, while biopsy showed pure sarcomatous tumor invading lung parenchymal. In both samples tumor cells coexpressed cytokeratin and vimentin. Peritoneal and hydrocele effusions contained aggregates of malignant mesothelial cells. Electron microscopy showed intermediate filaments, rare desmosomes and sparse microvilli. Morphological findings were consistent with a DMM, with a biphasic pattern in the pleura and an epithelial one in the peritoneum and tunica vaginalis. Although the possibility of a multicentric origin cannot be ruled out, clinical chronologic sequence suggests that the pleura was the primary involved site, followed by spread to peritoneum and tunica vaginalis.}, } @article {pmid8702248, year = {1996}, author = {Huncharek, M and Kelsey, K and Mark, EJ and Muscat, J and Choi, N and Carey, R and Christiani, D}, title = {Treatment and survival in diffuse malignant pleural mesothelioma; a study of 83 cases from the Massachusetts General Hospital.}, journal = {Anticancer research}, volume = {16}, number = {3A}, pages = {1265-1268}, pmid = {8702248}, issn = {0250-7005}, mesh = {Adult ; Aged ; Aged, 80 and over ; Combined Modality Therapy ; Female ; Humans ; Male ; Mesothelioma/*mortality/pathology/*therapy ; Middle Aged ; Pleural Neoplasms/*mortality/pathology/*therapy ; Prognosis ; Risk Factors ; Treatment Outcome ; }, abstract = {The influence of treatment on clinical outcome in pleural mesothelioma (PM) is uncertain. We studied 83 patients with PM treated at our institution to evaluate the impact of treatment modality on survival, Methods. Medical records of 83 patients with PM treated between 1978 and 1994 were reviewed. The following data were tabulated for each patient; age, sex, date of diagnosis, history of asbestos exposure, smoking history, method of diagnosis, histologic subtype, type of treatment and survival from diagnosis. Four treatment groups were analyzed; chemotherapy (C), surgery (S), combined modality (CM i.e. S + C with or without radiation therapy) and supportive care alone (SC). Survival curves were calculated and adjustment made for age. Survival curves were compared using Wilcoxon Chi-square analysis. Results. Seventy-one males and 12 females with a mean age of 67 years were analyzed. Seventy-five percent were smokers and 74% reported definite or probable asbestos exposure. Treatment groups did not vary according to smoking or asbestos history. The CM group and SC groups contained similar proportions of patients with epithelial tumors (54% v 56%). Median survival for patients in the CM group was 23.9 months versus 4.5 months among those receiving SC (p < 0.01). Discussion. This analysis suggest prolonged survival among patients with PM receiving CM versus SC or single modality treatment.}, } @article {pmid8624274, year = {1996}, author = {Muscat, JE and Huncharek, M}, title = {Dietary intake and the risk of malignant mesothelioma.}, journal = {British journal of cancer}, volume = {73}, number = {9}, pages = {1122-1125}, pmid = {8624274}, issn = {0007-0920}, support = {CA-32617/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Age Factors ; Aged ; Asbestos ; Body Mass Index ; Case-Control Studies ; Confidence Intervals ; Demography ; *Diet ; Female ; Fruit ; Humans ; Male ; Mesothelioma/*epidemiology/prevention & control ; Middle Aged ; Occupational Exposure ; Occupations ; Odds Ratio ; Risk Factors ; Sex Characteristics ; Sex Factors ; Smoking ; Socioeconomic Factors ; Vegetables ; Vitamins ; }, abstract = {A high consumption of fruit and vegetables reduces the risk of several types of cancer. There is little information on the association between dietary intake and mesothelioma. A hospital-based case-control study of 94 men and women with malignant mesothelioma and 64 control patients without cancer was conducted to determine the odds associated with consumption of carotenoid-containing fruits and vegetables. After statistical adjustment for occupational asbestos exposure, the odds ratio was 0.2 [95% confidence interval (CI) 0.1-0.8] for carrot consumption and 0.5 (95% CI 0.2-1.4) for tomato consumption. However, the frequency of consuming other foods that have a high vitamin A or carotenoid content was not associated with a decreased risk of cancer. These results provide some justification for the hypothesis that provitamin A or beta-carotene may decrease the risk of mesothelioma. The body mass index was unrelated to the risk of mesothelioma.}, } @article {pmid8603371, year = {1996}, author = {Huncharek, M and Kelsey, K and Muscat, J and Christiani, D}, title = {Parental cancer and genetic predisposition in malignant pleural mesothelioma: a case-control study.}, journal = {Cancer letters}, volume = {102}, number = {1-2}, pages = {205-208}, doi = {10.1016/0304-3835(96)04172-9}, pmid = {8603371}, issn = {0304-3835}, mesh = {Asbestos/adverse effects ; Case-Control Studies ; Female ; Humans ; Male ; Mesothelioma/etiology/*genetics ; Middle Aged ; Pleural Neoplasms/etiology/*genetics ; Smoking/adverse effects ; }, abstract = {Familial clustering of pleural mesothelioma (PM) has been previously reported suggesting that genetic factors (predisposition) may be involved in PM. We studied parental cancer history in a cohort of 39 cases of PM and 259 age matched controls to assess the possible influence of family history on PM risk. Cases consisted of 39 patients with PM treated at our institution between 1978 and 1993. An age frequency matched control group (by 5-year age groups) consisted of 259 subjects who were spouses or friends of patients undergoing resection of primary lung cancer. Data were obtained by interview of controls and interview of the patient or next of kin (usually spouse) for cases. The following data were obtained using a standard questionnaire and medical record review; age, sex, date of diagnosis, history of asbestos exposure, smoking history, method of diagnosis, histologic subtype, type of treatment, parental cancer history and tumor type. Cases and control frequency of parental cancer and site specific tumor frequency were compared using chi-square analysis. Twenty-eight (71%) cases reported a parental history of cancer versus 114 (44%) in the control group (P<0.01). Gastrointestinal malignancies were the predominant tumor type among parents of cases, i.e. 11 cases (40%) versus 25% of controls (P<0.01). No other tumor site showed an increased frequency among cases. These data suggest a possible role for family history in the development of PM. Genetic predisposition may be important in the etiology of this tumor.}, } @article {pmid8942254, year = {1996}, author = {Lee, HS and Phoon, WH and Wang, SY and Tan, KP}, title = {Occupational respiratory diseases in Singapore.}, journal = {Singapore medical journal}, volume = {37}, number = {2}, pages = {160-164}, pmid = {8942254}, issn = {0037-5675}, mesh = {Data Collection ; Humans ; Incidence ; Occupational Diseases/diagnosis/*epidemiology ; Respiratory Tract Diseases/*epidemiology/etiology ; Risk Factors ; Singapore/epidemiology ; }, abstract = {Occupational respiratory disease statistics in Singapore from 1970 to 1993 were reviewed. Silicosis was the most common occupational respiratory disease in the 1970s and 1980s. About 78% of the cases were from granite quarries. With progressive reduction in dust levels and the closure of some quarries, there has been a decline in cases. From 1990 to 1993, occupational asthma was the most common occupational respiratory disease and more cases are expected with increasing awareness of the condition. The most common causative agent was isocyanates accounting for about 34% of cases. Of the asbestosis and malignant mesothelioma cases, about 70%-80% were from the one and only asbestos cement factory. With the closure of this factory and the increasing restrictions on the use of asbestos, cases of asbestosis are expected to decline in the long term. However, malignant mesothelioma cases may continue to surface because of the long latent period and the potential risk with low and brief exposures to asbestos. It is important to probe for possible occupational exposures (both present and past) in a patient with respiratory symptoms or disease.}, } @article {pmid8901239, year = {1996}, author = {Dufresne, A and Loosereewanich, P and Armstrong, B and Thériault, G and Bégin, R}, title = {Inorganic particles in the lungs of five aluminum smelter workers with pleuro-pulmonary cancer.}, journal = {American Industrial Hygiene Association journal}, volume = {57}, number = {4}, pages = {370-375}, doi = {10.1080/15428119691014918}, pmid = {8901239}, issn = {0002-8894}, mesh = {Adult ; Aged ; Air Pollutants, Occupational/adverse effects/*analysis ; Aluminum/adverse effects/*analysis ; *Environmental Monitoring ; Humans ; Lung Neoplasms/*chemically induced/pathology ; Male ; *Metallurgy ; Middle Aged ; Occupational Diseases/*chemically induced/pathology ; Pleural Neoplasms/*chemically induced/pathology ; }, abstract = {This paper reports on the inorganic particles in the lungs of four workers who died from lung cancer and one who died from mesothelioma. All five workers were involved in different operations and activities in aluminum reduction plants. Retained fibrous and nonfibrous particles were evaluated by transmission electron microscopy and energy dispersive spectroscopy after lung digestion. Asbestos fibers, fragments of silicates, and metal-rich nonfibrous particles of chromium-cobalt and aluminum were detected. Conclusions drawn from the evaluation of the particles retained in the lungs of only five workers must be cautious. However, these results are consistent with the hypothesis that carcinogenic polycyclic aromatic hydrocarbons may not be the only contaminants that could explain excess mortality from malignant lung neoplasm in aluminum smelter workers.}, } @article {pmid8691657, year = {1996}, author = {Hiraoka, T and Ando, M and Shima, K and Kinuwaki, E and Kiyota, S and Futatsuka, M and Fujita, M}, title = {[Epidemiologic survey of pleural plaques among inhabitants of Matsubase exposed to asbestos].}, journal = {Nihon Kyobu Shikkan Gakkai zasshi}, volume = {34}, number = {4}, pages = {385-391}, pmid = {8691657}, issn = {0301-1542}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Asbestosis/*epidemiology/etiology ; *Environmental Exposure ; Female ; Humans ; Japan/epidemiology ; Male ; Middle Aged ; Pleural Diseases/*epidemiology/etiology ; Prevalence ; }, abstract = {A high prevalence of pleural plaques (41.5%, 148/357) was found during a mass screening for lung cancer in Matsubase town in 1988. The inhabitants of this town were carefully studied each year from 1988 to 1993. The vast majority (81.2%) of inhabitants over the age of 20 years underwent chest roentgenography at least once during this period. Pleural plaques were detected by CT in 938 subjects, which is 17.3% of those studied and 4.1% of the total population. A total of 89 had an occupational history of asbestos exposure, 64 (71.9%) of whom had pleural plaques. However, these subjects with occupational exposure accounted for only 6.8% of the 938 subjects, and therefore most of the pleural plaques seemed to have been caused by general environmental exposure. The incidence of plaques was greater in older subjects: among those in the seventh decade of life it was more than eight times higher than among those in the fourth decade of life. Anthophyllite was detected in the main asbestos mill. The concentrations of asbestos fibers in the air and water near the old asbestos mills and factories were not high. The death rates and the adjusted mortality rates due to lung cancer in Matsubase were lower than in surrounding towns and lower than in Kumamoto prefecture as a whole. These results indicate that there is now no environmental contamination by asbestos fibers in Matsubase town. No cases of malignant mesothelioma have been confirmed in this town during the past 17 years.}, } @article {pmid8664959, year = {1996}, author = {Danielsen, TE and Langård, S and Andersen, A}, title = {Incidence of cancer among Norwegian boiler welders.}, journal = {Occupational and environmental medicine}, volume = {53}, number = {4}, pages = {231-234}, pmid = {8664959}, issn = {1351-0711}, mesh = {Cohort Studies ; Humans ; Incidence ; Leukemia/chemically induced/epidemiology ; Lung Neoplasms/chemically induced/epidemiology ; Male ; Mesothelioma/chemically induced/epidemiology ; Neoplasms/*chemically induced/*epidemiology ; Norway/epidemiology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/chemically induced/epidemiology ; Prospective Studies ; *Welding ; }, abstract = {OBJECTIVES: The cancer incidence among 2957 boiler welders was investigated. The subjects were registered electrical welders from 1942 to 1981. A subcohort of 606 stainless steel welders was studied separately.

METHODS: The investigation was a historical prospective cohort study based on a national registry. The loss of follow up was 4.9%.

RESULTS: There were 625 deaths (659 expected). There were 269 cancer cases (264 expected). An excess of lung cancer was found; 50 cases v 37.5 expected. There were three cases of pleural mesotheliomas v 1.1 expected. The subcohort of stainless steel welders had six cases of lung cancer v 5.8 expected, and one case of pleural mesothelioma v 0.2 expected.

CONCLUSIONS: The welders in the study were assumed to represent a qualified work force. These welders had a small excess risk of lung cancer. The excess risk did not seem to be associated with stainless steel welding. Smoking and asbestos exposure were potential confounders.}, } @article {pmid8614876, year = {1996}, author = {King, JA and Wong, SW}, title = {Autopsy evaluation of asbestos exposure: retrospective study of 135 cases with quantitation of ferruginous bodies in digested lung tissue.}, journal = {Southern medical journal}, volume = {89}, number = {4}, pages = {380-385}, pmid = {8614876}, issn = {0038-4348}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestosis/*pathology ; Autopsy ; Female ; Humans ; Lung/*pathology ; Lung Neoplasms/pathology ; Male ; Mesothelioma/pathology ; Middle Aged ; Pulmonary Fibrosis/pathology ; Retrospective Studies ; }, abstract = {In recent years, there has been increased interest in documenting asbestos exposure. The pathologic sine qua non of asbestos exposure has been the presence of "asbestos bodies" in lung parenchyma. In this retrospective study of 135 autopsies done to determine asbestos exposure, ferruginous bodies in digested lung tissue were quantitated by a simplified sodium hypochlorite procedure on fresh or fixed tissue. Of the 131 digested specimens, 26 (20%) showed no ferruginous bodies, 34 (26%) had <5 ferruginous bodies per slide, 7 (5%) had 5 to 10 ferruginous bodies per slide, and 64 (49%) had >10 ferruginous bodies per slide. Ferruginous bodies were identified in hematoxylin-eosin stained sections of lung tissue in only 41 cases (30%). The digestion method described is a simple, reliable, and inexpensive method to assess ferruginous bodies.}, } @article {pmid8611410, year = {1996}, author = {Fear, NT and Roman, E and Carpenter, LM and Newton, R and Bull, D}, title = {Cancer in electrical workers: an analysis of cancer registrations in England, 1981-87.}, journal = {British journal of cancer}, volume = {73}, number = {7}, pages = {935-939}, pmid = {8611410}, issn = {0007-0920}, mesh = {Adult ; Age Factors ; Aged ; *Electricity ; Electrons ; England/epidemiology ; Female ; Humans ; Incidence ; Male ; Mesothelioma/epidemiology ; Middle Aged ; Neoplasms/*epidemiology ; Occupational Diseases/*epidemiology ; Pleural Neoplasms/epidemiology ; Registries ; Smoking ; }, abstract = {Associations between work in the electrical and electronic industry and cancer incidence were assessed using data for 371 890 cancers registered in England between 1981 and 1987, of which 7981 were in electrical workers. Proportional registration ratios (PRRs) were calculated, both with and without the commonest cancers, with adjustment for age, social class, cancer registry of origin and sex. Of four cancers previously linked with work in the electrical and electronic industry (leukaemia, brain, breast and melanoma), only two were significantly raised: leukaemia (PRR=124, 95% CI=109-142, based on 217 cases) and malignant brain cancer (PRR=118, 95% CI=103-136, based on 204 cases). A significantly increased risk was also observed for pleural cancer (PRR=201, 95% CI=167-241, based on 115 cases). The histology of almost 90% of pleural cancers was coded as mesothelioma, confirming the previously observed association between pleural cancer and exposure to asbestos in electrical workers. The extent to which workplace exposures to extremely low frequency electromagnetic fields explains the excesses seen here for leukaemia and brain cancer requires further study.}, } @article {pmid8608519, year = {1996}, author = {Cavazza, A and Travis, LB and Travis, WD and Wolfe, JT and Foo, ML and Gillespie, DJ and Weidner, N and Colby, TV}, title = {Post-irradiation malignant mesothelioma.}, journal = {Cancer}, volume = {77}, number = {7}, pages = {1379-1385}, doi = {10.1002/(SICI)1097-0142(19960401)77:7<1379::AID-CNCR24>3.0.CO;2-Y}, pmid = {8608519}, issn = {0008-543X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Child ; Female ; Humans ; Infant ; Male ; Mesothelioma/epidemiology/*etiology/pathology ; Middle Aged ; Neoplasms, Radiation-Induced/epidemiology/*etiology/pathology ; Neoplasms, Second Primary/epidemiology/*etiology/pathology ; Pleural Neoplasms/epidemiology/*etiology/pathology ; Radiotherapy/adverse effects ; SEER Program ; }, abstract = {BACKGROUND: Approximately 30 patients with malignant mesothelioma following radiotherapy have been described. Population-based studies of this occurrence have not been reported.

METHODS: Patients with malignant mesothelioma of the pleura were collected. All of the patients had a prior cancer and had received radiotherapy to the region in which the malignant mesothelioma developed. Data from the National Cancer Institute's Surveillance, Epidemiology and End Results Program and the Connecticut Tumor Registry were evaluated for cases of malignant mesothelioma of the pleura occurring in patients with a previous cancer. The literature on post-irradiation malignant mesotheliomas was reviewed.

RESULTS: Eight patients (4 men, 4 women) with malignant mesothelioma occurring in sites of radiotherapy for a prior tumor were identified. The mean age at diagnosis of mesothelioma was 45 years (range: 22-78 years), and the average interval between radiotherapy and the mesothelioma was 21 years (range: 11-29 years). Three of the patients had also received chemotherapy. Histologically, the mesotheliomas were epithelial in five cases, biphasic in one, and sarcomatous in one. One hundred forty-two patients were identified in the epidemiologic survey. The majority were men (89%), with a mean age for all patients of 68.5 years (range: 35-86 years) and a median latency between first cancer and mesothelioma of 4.3 years (range: 2 months-29.9 years).

CONCLUSIONS: Mesotheliomas rarely develop as second malignant neoplasms. Within a large, population-based survey of patients with cancer, temporal patterns and demographic features of most second primary mesotheliomas were similar to asbestos-related tumors, although the late effects of cancer treatment might have contributed to the occurrence of cancer in some patients.}, } @article {pmid9363126, year = {1996}, author = {Tsai, W and Morgan, WK}, title = {The pneumoconioses.}, journal = {Current opinion in pulmonary medicine}, volume = {2}, number = {2}, pages = {116-120}, doi = {10.1097/00063198-199603000-00007}, pmid = {9363126}, issn = {1070-5287}, mesh = {Asbestos, Amphibole/adverse effects ; Asbestosis/diagnosis/epidemiology ; Asia/epidemiology ; Australia/epidemiology ; Bronchoalveolar Lavage ; Coal Mining ; Europe/epidemiology ; Humans ; Incidence ; Magnetic Resonance Imaging ; Mesothelioma/epidemiology ; North America/epidemiology ; Occupational Exposure ; Pneumoconiosis/diagnosis/*epidemiology/prevention & control ; Population Surveillance ; Prevalence ; Silicosis/diagnosis/epidemiology ; }, abstract = {The stringent industrial hygiene regulations that have been introduced in North America, Europe, and Australasia have led to a decline in the incidence and prevalence of silicosis, coal workers' pneumoconiosis, and asbestosis. Although new cases of asbestosis are not occurring, an appreciable number of mesotheliomata are still being diagnosed, and there has yet been little, if any, decline in the latter tumor. These new cases are nearly entirely due to exposure to amphiboles in the 1940s and 1950s. It is expected that by about the year 2000 the incidence of mesothelioma will begin to decrease in the United States and Canada. Meanwhile there is an undue preoccupation with more and more sensitive methods of detecting asbestosis, silicosis, and coal workers' pneumoconiosis, eg, magnetic resonance imaging, bronchoalveolar lavage, and so forth. Much effort is being made in trying to detect disease in groups of workers with extremely low exposures and no symptoms. Smaller and smaller effects are being detected, with the ultimate aim appearing to be detecting nothing at all. Efforts should be made at surveying other populations exposed to agents that have recently been introduced and that could conceivably have long-term effects.}, } @article {pmid8882093, year = {1996}, author = {Egilman, DS and Goldin, AS and Goldin, GA}, title = {Mesothelioma: An unwarranted causal model.}, journal = {Journal of occupational and environmental medicine}, volume = {38}, number = {3}, pages = {239-240}, doi = {10.1097/00043764-199603000-00001}, pmid = {8882093}, issn = {1076-2752}, mesh = {Asbestos/adverse effects ; Humans ; Lung Neoplasms/epidemiology/*etiology ; Mesothelioma/epidemiology/*etiology ; Models, Theoretical ; Occupational Exposure/*adverse effects ; Reproducibility of Results ; Survival Rate ; }, } @article {pmid8740736, year = {1996}, author = {Pukkala, E and Saarni, H}, title = {Cancer incidence among Finnish seafarers, 1967-92.}, journal = {Cancer causes & control : CCC}, volume = {7}, number = {2}, pages = {231-239}, pmid = {8740736}, issn = {0957-5243}, mesh = {Adult ; Cohort Studies ; Female ; Finland/epidemiology ; Follow-Up Studies ; Humans ; Incidence ; Male ; Middle Aged ; *Naval Medicine ; Neoplasms/*epidemiology ; Occupational Diseases/*epidemiology ; Risk Factors ; Time Factors ; }, abstract = {A cohort of 30,940 male and 11,529 female seafarers registered in the files of Seafarers' Pension Fund in Finland was followed up through the Finnish Cancer Registry for cancer in 1967-92. Among male seafarers, there were 1,199 cases of cancer, which corresponds to the average cancer incidence in Finnish men. There was a statistically significant excess of non-melanoma skin cancer (standardized incidence ratio [SIR] = 1.8, 95 percent confidence interval [CI] = 1.2-2.5) and mesothelioma (SIR = 2.9, CI = 1.2-5.6) in the follow-up category of 20 or more years since the first employment. Alcohol-related cancers were increased among seafarers (SIR for cancer of the mouth and pharynx = 1.5; esophagus = 1.4; and liver = 1.5; combined CI = 1.1-1.9). Deck crews had a significantly high risk of cancer of the pancreas (SIR = 2.0) and also prostate after 10 years since first employment (SIR = 1.6). Occupational asbestos exposure among seafarers is likely strong enough to cause excess cases of mesothelioma but not of lung cancer. Occupational exposures also may be associated with increased risk of cancers of the kidney, pancreas, prostate and old-age brain cancer in some of the main occupational categories. Cumulative ultraviolet radiation likely doubles the risk of non-melanoma skin cancer among older men and repeated sunburns that of skin melanoma in ages below 30 (SIR among deck and engine crew = 4.6, CI = 3.1-6.5). Female ship personnel had a significantly elevated total cancer risk (observed number of cases = 732) which increased over follow-up time (SIR in the category > or = 20 years since the first employment was 1.3, CI = 1.1-1.5). This excess was attributable primarily to lung cancer (SIR = 2.6, CI = 2.0-3.3). Also cancers of the cervix uteri, vulva, and vagina showed significant excess after 10 to 20 years since first employment aboard.}, } @article {pmid8687108, year = {1996}, author = {Colt, HG and Astoul, P and Wang, X and Yi, ES and Boutin, C and Hoffman, RM}, title = {Clinical course of human epithelial-type malignant pleural mesothelioma replicated in an orthotopic-transplant nude mouse model.}, journal = {Anticancer research}, volume = {16}, number = {2}, pages = {633-639}, pmid = {8687108}, issn = {0250-7005}, mesh = {Adult ; Animals ; *Disease Models, Animal ; Humans ; Lymphatic Metastasis ; Male ; Mesothelioma/*pathology ; Mice ; Mice, Nude ; Neoplasm Transplantation/*methods ; Pleural Neoplasms/*pathology ; Transplantation, Heterologous ; }, abstract = {Malignant pleural mesothelioma is an aggressive tumor that is essentially unresponsive to standard medical and surgical therapies. Little is actually known about its biologic response to therapeutic interventions, in part because of a lack of a "patient-like" animal tumor model. Most experimental models thus far have been derived from inhalation or inoculation of asbestos fibers into animal subjects or by subcutaneous transplantation of human mesothelial cell lines into nude mice. These models are not representative of clinical malignant pleural mesothelioma. In this report, an animal model of human pleural malignant mesothelioma obtained by orthotopic transplantation of intact pleural tumor tissue into athymic nude mice is described. Pleural tumor obtained by thoracolscopy from a patient with epithelial-type malignant pleural mesothelioma was implanted as intact tissue by surgical orthotopic implantation (SOI) into the right pleural cavity of nude mice. Animals were sacrificed when moribund or 6 months after implantation. Tumor growth and regional spread in the mice evaluated at post-mortem examination mimicked the clinical pattern of progression of human disease. Histologic findings and the immunohistochemical profile were similar to those demonstrated on examination of thoracoscopic parietal pleural biopsy specimens and post-mortem examination of the original patient's tumor. This "patient-like" nude mouse model of epithelial-type malignant pleural mesothelioma, phenotypically similar to the original human tumor, should facilitate future investigation of tumorigenesis and metastatic potential of this neoplasm. The model should serve as a basis for assessing the impact of experimental and existing therapy on malignant mesothelioma.}, } @article {pmid8882441, year = {1996}, author = {Erika, V and Zoltán, S and Miklós, Z and Judit, A and Akos, L and Kálmán, K}, title = {[Malignant mesothelioma of the pleura].}, journal = {Orvosi hetilap}, volume = {137}, number = {5}, pages = {233-238}, pmid = {8882441}, issn = {0030-6002}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Autopsy ; Biopsy, Needle ; Carcinogens, Environmental ; Combined Modality Therapy ; Female ; Humans ; Hungary/epidemiology ; Male ; Mesothelioma/*chemically induced/mortality/pathology/therapy ; Middle Aged ; Neoplasm Staging ; Pleural Neoplasms/*chemically induced/mortality/pathology/therapy ; Radiography, Thoracic ; }, abstract = {Forty cases of malignant mesothelioma diagnosed from 1989 to 1994 at the Department of Pulmonology, Semmelweis Medical School were reviewed retrospectively. In 6 patients (15%) had a history of exposure to asbestos. The possibility of the malignant mesothelioma was raised by the clinical signs and the results of chest X-ray, chest computed tomography and sonography of the chest at their patients. Diagnosis was made by hystological examination of thoracoscopic or needle pleural biopsy in 15 and 8 cases, respectively, by cytological examination of fine needle pleural biopsy or pleural fluid in 7 and 6 cases, respectively, and by thoracotomy in 5 patients. Diagnosis was confirmed by multiple procedures in 11 patients. In six patients, diagnosis of malignant mesothelioma was made only by autopsy. The patients were staged according to Butchart et al. Longer survival was noted in the patients with earlier stages. Single or combined therapeutic modalities such as surgery (in 5 patients), chemotherapy (in 10 patients) and radiotherapy (in 3 patients) were used with additional symptomatic treatment in the majority of the cases. Pleurodesis also was done in 7 cases. There was no difference in survival among patients had received different treatment.}, } @article {pmid8821361, year = {1996}, author = {Barroetavena, MC and Teschke, K and Bates, DV}, title = {Unrecognized asbestos-induced disease.}, journal = {American journal of industrial medicine}, volume = {29}, number = {2}, pages = {183-185}, doi = {10.1002/(SICI)1097-0274(199602)29:2<183::AID-AJIM8>3.0.CO;2-T}, pmid = {8821361}, issn = {0271-3586}, mesh = {Asbestos/*adverse effects ; Asbestosis/diagnosis/*epidemiology ; British Columbia/epidemiology ; Diagnosis, Differential ; Disease Notification/statistics & numerical data ; Humans ; Lung Neoplasms/diagnosis/*epidemiology ; Mesothelioma/diagnosis/*epidemiology ; New South Wales/epidemiology ; Occupational Diseases/diagnosis/*epidemiology ; Pleural Neoplasms/diagnosis/*epidemiology ; Risk ; Workers' Compensation/statistics & numerical data ; }, abstract = {It is being slowly recognized that there is serious under-reporting of cancers that are occupationally related, in the sense that they would not have occurred without the occupational exposure. Data from the Workers' Compensation Boards of New South Wales in Australia and British Columbia in Canada relating to disease attributable to asbestos exposure indicate that in both jurisdictions the ratio of lung cancer cases to mesothelioma cases is much lower than epidemiological studies indicate must be occurring. Over the period from 1980 to 1994, if both jurisdictions are considered together, about 1,207 cases of lung cancer that would not have occurred without asbestos exposure went unrecognized as occupationally related. The data also suggest that it is unlikely that radiological asbestosis should be regarded as a necessary condition for there to be an increased risk of lung cancer following asbestos exposure.}, } @article {pmid8821355, year = {1996}, author = {Torén, K and Persson, B and Wingren, G}, title = {Health effects of working in pulp and paper mills: malignant diseases.}, journal = {American journal of industrial medicine}, volume = {29}, number = {2}, pages = {123-130}, doi = {10.1002/(SICI)1097-0274(199602)29:2<123::AID-AJIM2>3.0.CO;2-T}, pmid = {8821355}, issn = {0271-3586}, mesh = {Air Pollutants, Occupational/*adverse effects ; Humans ; *Industry ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Neoplasms/*etiology ; Occupational Diseases/*etiology ; Occupational Exposure/*adverse effects ; *Paper ; Pleural Neoplasms/etiology ; Risk Factors ; }, abstract = {This paper reviews the available literature regarding the work environment in pulp and paper mills and the risk for malignant diseases. An increased risk for lung cancer among pulp and paper mill workers has been reported. Most studies are inconclusive with regard to considerations of etiologic agents. However, maintenance workers seem to be at an increased risk for lung cancer, as well as for malignant mesothelioma, indicating that this occupational group was (is) exposed to asbestos. Workers exposed to chlorine compounds also seem to run an increased risk for lung cancer. An increased risk for malignant lymphomas among pulp mill workers is a constant finding. The increased risk is observed both among sulfite and sulfate workers, indicating a common exposure. Such an exposure could be wood dust, terpenes, or preservatives present in the wood. An increased risk for leukemias has been found in many studies carried out on pulp and paper workers, but the studies do not permit any conclusions about etiologic factors. In some studies an increased risk for stomach cancer has been found. However, the socioeconomic status of the workers is strongly related to stomach cancer, and factors, such as dietary habits, have not been taken into account in any of the reviewed studies. Hence, no further conclusions can be drawn regarding etiologic agents.}, } @article {pmid8734314, year = {1996}, author = {Fayemendy, L and Tulliez, M and Uzzan, E and Abelanet, R and Chaussade, S and Couturier, D}, title = {[Peritoneal mesothelioma revealed by episodes of recurrent spontaneous peritonitis].}, journal = {Gastroenterologie clinique et biologique}, volume = {20}, number = {1}, pages = {99-102}, pmid = {8734314}, issn = {0399-8320}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Colectomy ; Combined Modality Therapy ; Fatal Outcome ; Humans ; Male ; Mesothelioma/*complications/diagnostic imaging/pathology/therapy ; Middle Aged ; Peritoneal Neoplasms/*complications/diagnostic imaging/pathology/therapy ; Peritonitis/*etiology ; Recurrence ; Tomography, X-Ray Computed ; }, abstract = {A case of a malignant peritoneal mesothelioma revealed by recurrent episodes of peritonitis is reported. This presentation had never been described. A 54 year-old man presented successive episodes of appendicitis, cholecystitis and sigmoiditis associated with purulent aseptic peritonitis. There were no signs of immunodepression or vasculitis. Initial analysis of peritoneal biopsies showed non specific inflammation. Because of long-term asbestos exposure, these biopsies were reviewed. A diagnosis of peritoneal mesothelioma was made on subserous infiltration by mesothelioma cells, and confirmed by immunohistochemistry. The patient died ten months after the diagnosis of mesothelioma despite chemotherapy (cisplatine+interferon).}, } @article {pmid8664037, year = {1996}, author = {Hoekman, K and Tognon, G and Risse, EK and Bloemsma, CA and Vermorken, JB}, title = {Well-differentiated papillary mesothelioma of the peritoneum: a separate entity.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {32A}, number = {2}, pages = {255-258}, doi = {10.1016/0959-8049(95)00574-9}, pmid = {8664037}, issn = {0959-8049}, mesh = {Adult ; Cell Differentiation ; Cell Nucleus/pathology ; Female ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Mesothelioma/genetics/metabolism/*pathology ; Peritoneal Neoplasms/genetics/metabolism/*pathology ; Ploidies ; Pregnancy ; Pregnancy Complications, Neoplastic/metabolism/pathology ; }, abstract = {Three female patients with a diffuse well-differentiated papillary mesothelioma of the peritoneum are presented. They did not have a history of exposure to asbestos. The peritoneal biopsies were studied extensively, including electron microscopy, nuclear morphometry and DNA ploidy analysis. The results from these more sophisticated investigations confirmed the mesothelial origin and further characterised these lesions. One of the 3 patients has continuing elevated serum CA-125 levels, which increased transiently during and after pregnancy. All 3 patients have done well without therapy, 2 patients being alive and non-symptomatic 6 and 7 years after the initial diagnosis. It is important to distinguish this disorder from the malignant diseases of the peritoneum and the ovary. In view of the indolent course of this subtype of mesothelioma, avoidance of treatment is justified unless there is evidence of progressive disease.}, } @article {pmid8633733, year = {1996}, author = {Stayner, LT and Dankovic, DA and Lemen, RA}, title = {Occupational exposure to chrysotile asbestos and cancer risk: a review of the amphibole hypothesis.}, journal = {American journal of public health}, volume = {86}, number = {2}, pages = {179-186}, pmid = {8633733}, issn = {0090-0036}, mesh = {Animals ; Asbestos, Amphibole/*adverse effects/toxicity ; Asbestos, Serpentine/*adverse effects/toxicity ; Carcinogens ; Epidemiologic Methods ; Humans ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; *Occupational Exposure ; Rats ; Risk ; }, abstract = {OBJECTIVES: This article examines the credibility and policy implications of the "amphibole hypothesis," which postulates that (1) the mesotheliomas observed among workers exposed to chrysotile asbestos may be explained by confounding exposures to amphiboles, and (2) chrysotile may have lower carcinogenic potency than amphiboles.

METHODS: A critical review was conducted of the lung burden, epidemiologic, toxicologic, and mechanistic studies that provide the basis for the amphibole hypothesis.

RESULTS: Mechanistic and lung burden studies do not provide convincing evidence for the amphibole hypothesis. Toxicologic and epidemiologic studies provide strong evidence that chrysotile is associated with an increased risk of lung cancer and mesothelioma. Chrysotile may be less potent than some amphiboles for inducing mesotheliomas, but there is little evidence to indicate lower lung cancer risk.

CONCLUSIONS: Given the evidence of a significant lung cancer risk, the lack of conclusive evidence for the amphibole hypothesis, and the fact that workers are generally exposed to a mixture of fibers, we conclude that it is prudent to treat chrysotile with virtually the same level of concern as the amphibole forms of asbestos.}, } @article {pmid8633728, year = {1996}, author = {Cullen, MR}, title = {The amphibole hypothesis of asbestos-related cancer--gone but not forgotten.}, journal = {American journal of public health}, volume = {86}, number = {2}, pages = {158-159}, pmid = {8633728}, issn = {0090-0036}, mesh = {Asbestos, Amphibole/*adverse effects ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; }, } @article {pmid8630964, year = {1996}, author = {Heineman, EF and Bernstein, L and Stark, AD and Spirtas, R}, title = {Mesothelioma, asbestos, and reported history of cancer in first-degree relatives.}, journal = {Cancer}, volume = {77}, number = {3}, pages = {549-554}, doi = {10.1002/(SICI)1097-0142(19960201)77:3<549::AID-CNCR18>3.0.CO;2-4}, pmid = {8630964}, issn = {0008-543X}, mesh = {Asbestos/*toxicity ; Environmental Exposure ; Family ; Female ; Humans ; Male ; Mesothelioma/*genetics ; Pleural Neoplasms/*genetics ; Sex Factors ; }, abstract = {BACKGROUND: Although malignant mesothelioma is known to be strongly related to asbestos exposure, its relationship to familial factors is unclear.

METHODS: We compared reported histories of cancer in first-degree relatives, obtained from telephone interviews with the next-of-kin of 196 patients who had a pathologic diagnosis of mesothelioma, and with those from 511 decreased controls.

RESULTS: Among men exposed to asbestos, we found a statistically significant twofold elevation in the risk of mesothelioma for patients reporting cancer in two or more first-degree relatives. We found no significant elevation in women or among the small number of men without asbestos exposure. The next-of-kin of three patients (but no controls) reported a possible mesothelioma in a first-degree relative; asbestos exposure could not be ruled out in those relatives. Associations of asbestos with pleural mesothelioma were stronger among men with a reported family history of cancer than men without, although no statistical evidence of an interaction was detected.

CONCLUSIONS: These results provide suggestive, but limited, evidence that a family history of cancer may be a risk factor for mesothelioma, or may indicate an increased susceptibility to mesothelioma given asbestos exposure.}, } @article {pmid8564122, year = {1996}, author = {Dufresne, A and Bégin, R and Churg, A and Massé, S}, title = {Mineral fiber content of lungs in patients with mesothelioma seeking compensation in Québec.}, journal = {American journal of respiratory and critical care medicine}, volume = {153}, number = {2}, pages = {711-718}, doi = {10.1164/ajrccm.153.2.8564122}, pmid = {8564122}, issn = {1073-449X}, mesh = {Aged ; Asbestos ; Electron Probe Microanalysis ; Humans ; Iron ; Lung/*pathology ; Mesothelioma/*pathology ; Microscopy, Electron ; Middle Aged ; *Mineral Fibers ; Occupational Diseases/*pathology ; Peritoneal Neoplasms/*pathology ; Pleural Neoplasms/*pathology ; Quebec ; Workers' Compensation ; }, abstract = {Asbestos fibers (AF) and ferruginous bodies (FB) in lung parenchyma from 50 workers seeking compensation from the Workers' Compensation Board of Québec for pleural or peritoneal mesothelioma were analyzed using transmission electron microscopy (TEM) equipped with energy-dispersive spectrometer (EDS) and phase-contrast microscopy (PCM). These workers had been occupationally exposed in mining and milling activities (12 were from Asbestos Township and 11 from Thetford Mines) and 27 were from other types of industry (asbestos factory, shipyard, etc.). For comparison, analyses of lung tissue at autopsy were done in a group of 49 subjects from a reference population. A 95% confidence interval upper limit of 540 AF < 5 microns/mg and a 95% confidence interval upper limit of 161 AF > or = 5 microns/mg dried lung tissue were found for the reference population. Similarly, a concentration of FB of 142 FB/g constituted the upper limit of detectable FB in the lungs of the reference population. Forty-eight of the 50 workers with mesothelioma had either a ferruginous body or total asbestos fiber count greater than the 95% confidence interval for the reference population; the remaining two had amosite and/or crocidolite concentrations greater than the 95% confidence interval for the reference population. The fiber types were different in the three groups, with the lungs of workers from Thetford Mines containing only chrysotile and tremolite, those from Asbestos Township containing chrysotile, tremolite, amosite, and crocidolite, and those in other industries containing largely amosite and crocidolite. We conclude that in this population of workers seeking compensation for mesothelioma, fiber analysis confirmed occupational asbestos exposure in every case. The fiber types responsible for the tumors are probably different in the three different groups.}, } @article {pmid9216805, year = {1996}, author = {Manavoğlu, O and Orhan, B and Evrensel, T and Ozçelik, T and Yolcu, I and Kunt, E}, title = {Malignant peritoneal mesothelioma following asbestos exposure.}, journal = {Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer}, volume = {15}, number = {2-4}, pages = {191-194}, pmid = {9216805}, issn = {0731-8898}, mesh = {Asbestos/*adverse effects ; Biomarkers, Tumor/blood ; Female ; Humans ; Mesothelioma/*chemically induced/diagnosis ; Middle Aged ; Peritoneal Neoplasms/*chemically induced/diagnosis ; }, abstract = {Clinical, epidemiological, and pathological studies have demonstrated that asbestosis plays a major role in the etiology of mesothelioma. The direct exposure of workers in industrialized countries to asbestos fibers and nonoccupational household contact elevate the risk of malignant mesothelioma. An increased risk has been found in certain geographic areas of Turkey due to the presence of asbestos deposits and the use of the material known as "white soil" as an insulation. We present a malignant mesothelioma case from rural eastern Turkey with a history of asbestos exposure from using "white soil". We review the epidemiological aspects of asbestos as they relate to mesothelioma.}, } @article {pmid9216804, year = {1996}, author = {Bariş, B and Demir, AU and Shehu, V and Karakoca, Y and Kisacik, G and Bariş, YI}, title = {Environmental fibrous zeolite (erionite) exposure and malignant tumors other than mesothelioma.}, journal = {Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer}, volume = {15}, number = {2-4}, pages = {183-189}, pmid = {9216804}, issn = {0731-8898}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Environmental Pollutants/*adverse effects ; Female ; Humans ; Infant ; Male ; Mesothelioma/mortality ; Middle Aged ; Neoplasms/*chemically induced/*mortality ; Turkey ; Zeolites/*adverse effects ; }, abstract = {We studied the mortality in three villages in the Cappadocian region of Central Anatolia, Karain, Tuzköy, and Sarihidir, which were exposed to fibrous zeolite (erionite), a known carcinogen more potent than the amphibole asbestos. Between 1970 and 1994, there were 305 deaths in Karain, and 177 (58%) were cancer related, including 150 (49.2%) malignant pleural mesothelioma, seven (2.3%) malignant peritoneal mesothelioma, and six (1%) gastroesophageal carcinoma. Four deaths (1.3%) from lung cancer included two nonsmoking females. There were three cases (1%) of leukemia and six of other malignancies (1.9%). Between 1980 and 1994, there were 519 deaths in Tuzköy (T) and Sarihidir (S) (T = 432, S = 87). Of these, 257 were cancer related, and included 120 cases of malignant pleural mesothelioma and 64 cases of malignant peritoneal mesothelioma. Intraabdominal carcinoma was noted in 29 patients and 14 patients had lung cancer (four of whom were nonsmoking women). There were five cases of gastroesophageal cancer, five deaths due to leukemia, and 16 cases of various malignancies. These mortality figures support the hypothesis that erionite fibers cause cancer other than mesothelioma and lung cancer. Mineralogic analyses of the tissues should be performed to demonstrate this relationship.}, } @article {pmid9216803, year = {1996}, author = {Cöplü, L and Dumortier, P and Demir, AU and Selçuk, ZT and Kalyoncu, F and Kisacik, G and DeVuyst, P and Sahin, AA and Bariş, YI}, title = {An epidemiological study in an Anatolian village in Turkey environmentally exposed to tremolite asbestos.}, journal = {Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer}, volume = {15}, number = {2-4}, pages = {177-182}, pmid = {9216803}, issn = {0731-8898}, mesh = {Adult ; Aged ; Air Pollutants/*adverse effects ; Asbestos, Amphibole/*adverse effects ; Female ; Humans ; Male ; Mesothelioma/*epidemiology/pathology ; Middle Aged ; Pleural Neoplasms/*epidemiology/pathology ; Rural Population ; Turkey/epidemiology ; }, abstract = {After several cases of malignant pleural mesothelioma (MPM) were detected in the village of Kureyşler in the Kütahya district of western Turkey, an epidemiological study was conducted. A questionnaire was completed by 124 villagers who were older than 20 years and standard posteroanterior chest X-rays were taken. The films were evaluated by three chest physicians. Samples of the white stucco that had been used by almost all villagers for indoor painting for many years were mineralogically examined. Chest X-rays showed that 23 (18%) had pleural plaques and calcifications compatible with asbestos exposure. Male sex and old age were associated with occurrence of pleural plaques. An analysis of white stucco samples revealed tremolite asbestos. In conclusion, tremolite fibers might be the cause of the high incidence of pleural plaques and MPM cases in the village of Kureyşler.}, } @article {pmid9132805, year = {1996}, author = {Szeszenia-Dabrowska, N and Szymczak, W and Wilczyńska, U}, title = {[Prevalence of pleural malignant mesothelioma in Poland in 1980-1993].}, journal = {Przeglad epidemiologiczny}, volume = {50}, number = {4}, pages = {447-455}, pmid = {9132805}, issn = {0033-2100}, mesh = {Adult ; Age Factors ; Aged ; Asbestos/adverse effects ; Female ; Humans ; Male ; Mesothelioma/etiology/*mortality/pathology ; Middle Aged ; Pleura/*pathology ; Pleural Neoplasms/epidemiology/etiology/pathology ; Poland/epidemiology ; Prevalence ; Retrospective Studies ; Sex Factors ; Survival Rate ; }, abstract = {Malignant pleural mesothelioma is subject of special interest for environmental epidemiologists due to its proven cause-effect relationship with the exposure to asbestos dust, particularly crocidolite. The paper discusses the prevalence trends and geographical distribution of pleural mesothelioma in Poland based on the death rate analysis. In 1993 the crude death rate for that neoplasm was found to be 4.48 per 1 million for men and 3.14 per 1 million for women. While interpreting the numerical data, such aspects were considered as the problems with histopathological diagnosis of pleural mesothelioma; the long latency period of 30-40 years; and consequently, the possibility that for the male population the results may have been affected by other causes of death owing to its relatively short average lifespan. The volume and types of asbestos used in Poland were also taken into account.}, } @article {pmid9091768, year = {1996}, author = {Krajnow, A}, title = {[The biological effect of fireproof ceramic fibers--literature review].}, journal = {Medycyna pracy}, volume = {47}, number = {6}, pages = {663-675}, pmid = {9091768}, issn = {0465-5893}, mesh = {Animals ; Ceramics/*toxicity ; Flame Retardants/adverse effects ; Macrophage Activation ; Male ; Mesothelioma/*etiology ; Mineral Fibers/*adverse effects ; Particle Size ; }, abstract = {The work presents reports, selected from the world literature, on the studies of biological effect of refractory ceramic fibres, carried out on experimental animals. The discrepancy between the results of studies performed may originate from differences in the distribution of fibre sizes or the durability of fibres in the organism and their surface properties which, in turn, depend on the chemical composition of fibres. In all studies discussed, ceramic fibres generally activated macrophages and they were characterised by a moderate fibrotic activity. A statistically significant increase in the incidence of tumor (mesothelioma) observed in several very important experimental studies may suggest that some types of refractory ceramic fibres show a similar carcinogenic potential to that of natural asbestos: crocidolite or chrysotile.}, } @article {pmid8999467, year = {1996}, author = {Kotela, I and Laskowicz, K and Plezia, B}, title = {[Consequences of exposure to asbestos dust].}, journal = {Przeglad lekarski}, volume = {53}, number = {8}, pages = {631-633}, pmid = {8999467}, issn = {0033-2240}, mesh = {Adult ; Air Pollutants/*adverse effects ; Air Pollutants, Occupational/adverse effects ; Asbestos/*adverse effects ; Chemical Industry ; Dust/*adverse effects ; Fatal Outcome ; Humans ; Male ; Mesothelioma/*etiology ; Middle Aged ; Pleural Neoplasms/*etiology ; }, abstract = {Mesotheliomas of pleura are neoplasms that rarely occur. Their etiology is connected with occupational exposure as well as environmental contact with asbestos dust. In this work, two cases of mesotheliomas of pleura are presented: first one with occupational exposure, the other one with environmental exposure. An increased number of mesothelioma diseases has been emphasised and endangerment of inhabitants health living closely to asbestos processing factory as well.}, } @article {pmid8919266, year = {1996}, author = {Friemann, J and Varnai, M and Sutter, C and Hohr, B and Behrens, A and Althoff, GH and Schilpkoter, HW}, title = {Differential diagnosis of malignant tumours in the abdominal cavity of rats after intraperitoneal injection of crocidolite or benzo[a]pyrene.}, journal = {Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie}, volume = {48}, number = {1}, pages = {13-17}, doi = {10.1016/S0940-2993(96)80085-6}, pmid = {8919266}, issn = {0940-2993}, mesh = {Abdominal Neoplasms/chemically induced/*diagnosis/*pathology ; Animals ; Asbestos, Crocidolite/administration & dosage/*toxicity ; Benzo(a)pyrene/administration & dosage/*toxicity ; Carcinogens/*toxicity ; Diagnosis, Differential ; Female ; Histiocytoma, Benign Fibrous/chemically induced/diagnosis/pathology ; Injections, Intraperitoneal ; Rats ; Rats, Wistar ; }, abstract = {In our investigation (i.p. test), crocidolite and benzo[a]pyrene, both caused a progression from initially reactive, then autonomously transformed proliferation of myofibroblasts and undifferentiated mesenchymal cells to malignant, multidirectionally differentiated (desmin and ED-1 positive) fibro-histiocytic tumours. Immunohistochemically these tumours showed no morphological characteristics (for example co-expression of vimentin and keratin in spindle-shaped tumour cells) of human asbestos-associated malignant mesotheliomas. On the other hand many tumour cells induced by crocidolite and benzo[a]pyrene had an ultrastructural appearance resembling fibroblasts and myofibroblasts. These have been demonstrated in only a few desmoplastic and sarcomatous mesotheliomas in human beings. None of the tumours revealed the typical ultrastructural features of epitheloid or transitional mesotheliomas. Apparently, both carcinogenic substances induce the transformation of undifferentiated pluripotent mesenchymal cells in rat peritoneum, regardless of their localization in the submesothelial compartment or perivascular connective tissue (preferentially after crocidolite application) or in the connective tissue pseudocapsule of major benzo[a]pyrene containing beeswax/tricaprylin depots in the mesometrium and mesenterial fatty tissue. In this way asbestos fibres in this animal experiment do not seem to induce an arrest in differentiation of intermediate or immature mesothelial cells as supposed formerly, but rather affect undifferentiated mesenchyme cells and myofibroblasts. This is an explanation for the immunohistochemical expression of markers of muscular differentiation in these tumour cells, which is known to occur in human malignant fibro-histiocytic tumours. If supplementary immunohistochemical investigations with different keratin antibodies also fail to confirm the mesothelial differentiation of the tumours induced in our i.p. test, the decision to call them "mesotheliomas" should be reconsidered. Further immuno-transmission-electron microscopical investigations with intermediate filament or macrophage antibodies are needed to clarify whether the term malignant "fibrohistiocytic sarcoma", "mesenchymoma" or "mesothelioblastoma" would be more correct from the morphological point of view.}, } @article {pmid8919265, year = {1996}, author = {Roller, M and Pott, F and Kamino, K and Althoff, GH and Bellmann, B}, title = {Results of current intraperitoneal carcinogenicity studies with mineral and vitreous fibres.}, journal = {Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie}, volume = {48}, number = {1}, pages = {3-12}, doi = {10.1016/S0940-2993(96)80084-4}, pmid = {8919265}, issn = {0940-2993}, mesh = {Abdominal Neoplasms/chemically induced ; Animals ; *Carcinogenicity Tests ; Dose-Response Relationship, Drug ; Dust/adverse effects ; Female ; Injections, Intraperitoneal ; Male ; Mesothelioma/chemically induced ; Mineral Fibers/*toxicity ; Rats ; Rats, Wistar ; }, abstract = {The study includes some 50 groups of male or female Wistar rats tested in three series. Except for one untreated group and 3 vehicle control groups, the animals were injected intraperitoneally (i.p.) once or repeatedly with dust suspensions and then examined, after lifetime observation up to 30 months, for tumours in the abdominal cavity. 1 granular dust (silicon carbide), 2 asbestos dusts (crocidolite, tremolite) and 11 vitreous fibre dust samples were administered. 5 of the vitreous fibre types were fine fibre fractions from 4 commercial insulation wools and 1 experimental wool, the others were prepared by milling glass microfibres, which have, per se, a small diameter range. The dosage per rat differed over a wide range in accordance with experience from earlier studies. The lowest dose was 0.04 x 10(9) crocidolite fibres in 0.5 mg dust, and the highest amounted to 20 x 10(9) glass fibres in 1000 mg divided into 40 weekly injections. Two mesotheliomas were found in a total of 395 rats treated with saline or granular silicon carbide (250 or 1000 mg). Eleven fibre dusts produced dose-dependent mesotheliomas at rates of up to 97 %, but the calculated fibre number > 5 micrometers in length required for inducing a 25 % tumour risk differed between the fibre samples tested in the relation of 1 to about 1000. UICC-like crocidolite heads the ranking order; the glass fibre B-01, which possesses a low durability in the body, ends it together with a rather thin sample of glass fibre type B-09. The stone fibre MMVF-21 takes a high place in the ranking order, similar to the tremolite sample. The results correspond to those of earlier i.p. tests.}, } @article {pmid8886804, year = {1996}, author = {Kinnula, VL and Pietarinen-Runtti, P and Raivio, K and Kahlos, K and Pelin, K and Mattson, K and Linnainmaa, K}, title = {Manganese superoxide dismutase in human pleural mesothelioma cell lines.}, journal = {Free radical biology & medicine}, volume = {21}, number = {4}, pages = {527-532}, doi = {10.1016/0891-5849(96)00049-4}, pmid = {8886804}, issn = {0891-5849}, mesh = {Analysis of Variance ; Blotting, Northern ; Cell Line ; Humans ; Lung Neoplasms/*enzymology/pathology ; Mesothelioma/*enzymology/pathology ; Neoplasm Metastasis ; Pleural Neoplasms/*enzymology/pathology ; RNA, Messenger/metabolism ; Superoxide Dismutase/biosynthesis/*metabolism ; *Transcription, Genetic ; Tumor Cells, Cultured ; }, abstract = {Mesothelioma is a malignant pleural or intraperitoneal tumor attributable to asbestos exposure in more than 80% of the cases. Manganese superoxide dismutase (MnSOD), a mitochondrial superoxide radical scavenging enzyme, is low in most tumors but is known to be induced by asbestos fibers and certain cytokines. Induction of MnSOD may be associated in asbestos-related pulmonary diseases in vivo. We investigated here MnSOD specific activity and MnSOD mRNA level using healthy human lung tissue, SV40-transformed human pleural mesothelial cells (Met5A), and six human malignant mesothelioma cell line cells. Total SOD (CuZnSOD + MnSOD) and MnSOD activities were 20.0 +/- 4.8 U/mg protein and 3.2 +/- 1.2 U/mg protein in healthy human lung tissue, and 25.6 +/- 10.7 U/mg and 3.8 +/- 1.0 U/mg in Met5A cells, respectively. In four mesothelioma cell lines MnSOD activity was significantly elevated, the highest activity (30.1 +/- 8.2 U/mg) was almost 10-fold compared to the activity in Met5A cells. The steady state mRNA level of MnSOD was low in Met5A cells and markedly higher in all mesothelioma cell lines roughly in proportion with enzyme activities. Cytotoxicity experiments, which were conducted in four cell lines, indicated that cells containing high MnSOD mRNA level and activity were resistant to the mitochondrial superoxide-producing agent menadione. In conclusion, our results suggest that human mesothelioma may express high levels of MnSOD, which is associated with high oxidant resistance of these cells.}, } @article {pmid8869527, year = {1996}, author = {Schneider, J and Straif, K and Woitowitz, HJ}, title = {Pleural mesothelioma and household asbestos exposure.}, journal = {Reviews on environmental health}, volume = {11}, number = {1-2}, pages = {65-70}, doi = {10.1515/reveh.1996.11.1-2.65}, pmid = {8869527}, issn = {0048-7554}, mesh = {Adult ; Aged ; Air Pollution, Indoor/*adverse effects ; Asbestos/*adverse effects ; *Family Health ; Female ; Germany ; Household Work ; Humans ; Lung Neoplasms/*etiology ; Male ; Mesothelioma/*etiology ; Middle Aged ; }, abstract = {This article discusses the development of asbestos-induced malignant mesotheliomas after non-occupational environmental exposure to asbestos through contact with occupationally exposed household members. In our policlinic, we have seen six fatal pleural mesothelioma cases (five wives and one son of asbestos-industry workers) with no history of occupational asbestos exposure. In five women, a causal relation was established between the fatal disease and inhalation of asbestos fibers while cleaning the contaminated work-clothes and shoes of their husbands at home. The son had also been exposed to asbestos throughout his childhood during daily visits with his father at the workplace.}, } @article {pmid8832292, year = {1996}, author = {Collingwood, KW and Raabe, GK and Wong, O}, title = {An updated cohort mortality study of workers at a northeastern United States petroleum refinery.}, journal = {International archives of occupational and environmental health}, volume = {68}, number = {5}, pages = {277-288}, pmid = {8832292}, issn = {0340-0131}, mesh = {Adult ; Aged ; *Chemical Industry ; Cohort Studies ; Confidence Intervals ; Female ; Humans ; Male ; Middle Aged ; Occupational Diseases/etiology/*mortality/pathology ; Petroleum/*adverse effects ; Risk Factors ; Survival Rate ; Time Factors ; United States ; }, abstract = {An update of a cohort study of 4855 employees at a Paulsboro, New Jersey refinery was conducted to further examine mortality patterns. The earlier study investigated refinery workers employed for a minimum of 1 year between 1 January 1946 and 1 January 1979. The vital status of these workers was ascertained through 1979. The update extended enrollment in the study and vital status follow-up for an additional 8 years (1980-1987). As in the previous study, mortality from all causes [standardized mortality ratio (SMR) = 87; 95% confidence interval (95% CI): 83-91] was significantly lower than expected compared with the general population. Total cancer mortality was also lower than expected (SMR = 96; 95% CI: 86-106). A borderline significant mortality increase in prostatic cancer was found (SMR = 144; 95% CI: 106-190). This increase was similar to the nonsignificant increase reported in the original study (SMR = 135; 95% CI: 90-196). The excess was of comparable magnitude among white males and nonwhite males, although it was not significant for the latter. Detailed analysis indicated that the prostatic cancer was not likely to be related to employment at the refinery. Mortality from lymphatic and hematopoietic cancers was similar to the expected mortality. Mortality from overall leukemia was as expected and detailed analyses by specific cell type showed no increase. An increase in mortality occurred from non-Hodgkin's lymphoma among male workers (SMR = 132; 95% CI: 74-217). The increase was not statistically significant and unlikely to be associated with refinery employment. Mortality from multiple myeloma among male employees was lower than expected (SMR = 74; 95% CI: 20-190). Mortality from asbestos-related diseases (pulmonary fibrosis, lung cancer, malignant mesothelioma) was also lower than expected among male workers. No cause-specific mortality was found to be associated with duration of employment at the refinery, including several causes which have been reported to be elevated in previous studies. The findings of this updated study indicate, as in the previous report, the generally favorable mortality experience of Paulsboro refinery workers.}, } @article {pmid8816862, year = {1996}, author = {Mossman, BT and Kamp, DW and Weitzman, SA}, title = {Mechanisms of carcinogenesis and clinical features of asbestos-associated cancers.}, journal = {Cancer investigation}, volume = {14}, number = {5}, pages = {466-480}, doi = {10.3109/07357909609018904}, pmid = {8816862}, issn = {0735-7907}, mesh = {Asbestos/*adverse effects ; Genes, p53 ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Proto-Oncogenes ; }, abstract = {Exposure to asbestos, particularly members of the amphibole subgroup (crocidolite, amosite), is associated with the development of malignant mesothelioma and lung cancer. Although management of asbestos in buildings and increased regulation of asbestos in workplace settings are viable approaches to the prevention of disease, the prognosis of asbestos-associated tumors is generally dismal. Moreover, although a vast amount of information is available on the responses of cells and tissues to fibers, understanding the pathogenesis of asbestos-associated malignancies is hampered by the complexity of and differences between various fiber types. Multiple interactions between components of cigarette smoke and asbestos may be important in the development of lung cancer. In this article, the general properties of asbestos fibers will be discussed with an emphasis on chemical and physical features implicated in tumorigenesis. We will then provide a brief overview of the clinical features and treatment of cancers associated with exposure to asbestos. Finally, we will review recent experimental data providing some insight into the cellular and molecular mechanisms of carcinogenesis by asbestos.}, } @article {pmid8808046, year = {1996}, author = {Tsai, SP and Waddell, LC and Gilstrap, EL and Ransdell, JD and Ross, CE}, title = {Mortality among maintenance employees potentially exposed to asbestos in a refinery and petrochemical plant.}, journal = {American journal of industrial medicine}, volume = {29}, number = {1}, pages = {89-98}, doi = {10.1002/(SICI)1097-0274(199601)29:1<89::AID-AJIM11>3.0.CO;2-W}, pmid = {8808046}, issn = {0271-3586}, mesh = {Adult ; Asbestos/*adverse effects ; Cause of Death ; Cohort Studies ; Humans ; Male ; Mesothelioma/etiology/*mortality ; Neoplasms/etiology/*mortality ; Occupational Diseases/etiology/*mortality ; *Petroleum ; Time Factors ; }, abstract = {This paper reports the mortality experience from 1948 to 1989 of 2,504 maintenance employees who had a minimum of one year of employment in jobs with potential exposure to asbestos at a Texas refinery and petrochemical plant. For the purposes of this study, "potential exposure" is equated with those jobs or crafts having the greatest direct potential proximity to, or which worked directly with, asbestos-containing materials, especially asbestos-containing thermal insulation. Approximately one-half of the study population had 10 years or longer potential exposure, and 80% had their first potential exposure before 1970. The total population exhibited significantly lower mortality for all causes, the standardized mortality ratio (SMR = 77); and for all cancer (SMR = 85), as compared to residents in the surrounding communities. Statistically significant deficits in mortality were also observed in a number of noncancerous diseases such as heart disease (SMR = 78; 95% CI = 69-88), nonmalignant respiratory disease (SMR = 70; 95% CI = 50-95), and cirrhosis of the liver (SMR = 44; 95% CI = 22-79). Mortality among employees who had 20 years or longer since their first potential exposure was also examined; the pattern of mortality was similar to that exhibited by the total cohort, with a slight increase in the SMR for most of the causes. The only statistically significant excess of mortality found was a fourfold increase in mesothelioma (5 observed and 1.2 expected deaths) the SMR was 428 (95% CI = 139-996) for the total cohort and was 469 (95% CI = 152-1093) for those who had 20 years or more since first potential exposure. In contrast to asbestos industry worker studies, mortality for lung cancer was substantially lower than the general population (SMR = 81; 95% CI = 63-103). The observed number of deaths for cancer of the larynx was virtually the same as expected (3 observed vs. 2.8 expected). This study also showed decreased mortality for cancers of gastrointestinal organs such as the esophagus (SMR = 78), stomach (SMR = 63), large intestine (SMR = 91), rectum (SMR = 55), or pancreas (SMR = 90)--cancers that have been reported to be elevated in studies of various industry workers directly exposed to asbestos.}, } @article {pmid8806096, year = {1996}, author = {Pass, HI and Mew, DJ}, title = {In vitro and in vivo studies of mesothelioma.}, journal = {Journal of cellular biochemistry. Supplement}, volume = {24}, number = {}, pages = {142-151}, doi = {10.1002/jcb.240630509}, pmid = {8806096}, issn = {0733-1959}, mesh = {Animals ; Asbestos/adverse effects ; Chromosome Aberrations ; Culture Media ; Cytokines/biosynthesis/genetics ; DNA, Neoplasm/genetics ; Gene Amplification ; Genes, p53 ; Growth Substances/genetics ; Humans ; Mesothelioma/etiology/genetics/*pathology ; Mice ; Mice, Nude ; Neoplasm Proteins/biosynthesis/genetics ; Neoplasm Transplantation ; Oncogenes ; Pleural Neoplasms/etiology/genetics/*pathology ; Transplantation, Heterologous ; Tumor Cells, Cultured/drug effects/transplantation ; }, abstract = {Pleural mesothelioma is an asbestos-related malignancy characterized by progressive local growth, late metastases, and median survivals between 8 and 18 months. It is only recently that the in vitro and in vivo characteristics of the malignancy has been investigated. These investigations have been aided by the development of cell lines from patients with the disease, as well as lines developed from asbestos-exposed animals. Nude mouse models constructed with subcutaneous, intraabdominal, or intrathoracic innoculation of cultured cell lines or fresh tumor have been used for evaluating response to innovative therapies. Karyotyping has been performed on a number of cell lines and multiple abnormalities involving many chromosomes have been identified. Aneuploidy is commonly seen, along with reported non-random patterns of chromosomal aberrations. The role of tumor suppressor genes, including p53 is controversial. Multiple growth factors including PDGF are being investigated for a possible paracrine/autocrine loop, and PDGF receptors seem to be differentially expressed in mesothelioma cells compared to normal mesothelial cells. The role of cytokines in the pathophysiology of the disease, secreted either by the tumor cells themselves or by monocyte/macrophages in the local tumor environment, remains to be defined.}, } @article {pmid8791130, year = {1996}, author = {Pass, HI and Kennedy, RC and Carbone, M}, title = {Evidence for and implications of SV40-like sequences in human mesotheliomas.}, journal = {Important advances in oncology}, volume = {}, number = {}, pages = {89-108}, pmid = {8791130}, issn = {0883-5896}, mesh = {Adult ; Animals ; Antibodies, Viral/blood ; Antigens, Polyomavirus Transforming/genetics/immunology/physiology ; Asbestos/adverse effects ; Asbestosis/complications ; Brain Neoplasms/virology ; Cell Transformation, Viral ; Child ; Cocarcinogenesis ; Cricetinae ; DNA, Neoplasm/genetics ; DNA, Viral/analysis ; Drug Contamination ; Follow-Up Studies ; Genes, Viral ; Humans ; Immunotherapy ; Macaca ; Mesocricetus ; Mesothelioma/epidemiology/etiology/genetics/therapy/*virology ; Mice ; Middle Aged ; Neoplasms, Experimental/virology ; Oncogenes ; Papillomavirus Infections/transmission ; Pleural Neoplasms/epidemiology/etiology/genetics/therapy/*virology ; Poliovirus Vaccine, Inactivated/adverse effects ; Polyomavirus/genetics/isolation & purification/*pathogenicity ; Simian virus 40/*genetics/immunology/pathogenicity/physiology ; Smoking/adverse effects ; Species Specificity ; Tumor Virus Infections/transmission ; Virus Replication ; }, } @article {pmid8732113, year = {1996}, author = {Zhang, D and Zhang, R and Zhang, D}, title = {[Diagnosis and treatment of pleural mesothelioma: a report of 40 cases].}, journal = {Zhonghua zhong liu za zhi [Chinese journal of oncology]}, volume = {18}, number = {1}, pages = {48-50}, pmid = {8732113}, issn = {0253-3766}, mesh = {Adolescent ; Adult ; Aged ; Combined Modality Therapy ; Female ; Humans ; Male ; Mesothelioma/*diagnosis/*surgery ; Middle Aged ; Pleural Neoplasms/*diagnosis/*surgery ; }, abstract = {Forty patients with pleural mesothelioma confirmed pathologically including 2 benign and 38 malignant lesions are reported. In the 38 malignant mesotheliomas, 12 were histopathologically defined while the rest were unclassified. In this series, 33 surgical resections and 3 thoracotomy biopsies were carried out, whereas 4 patients were not operated. In 36 thoracotomies, there was one death with an operative mortality of 2.8% (1/36). Of 33 surgical resections, 10 (31%) received combined therapy. Of the 3 thoracotomy biopsy cases, postoperative irradiation was given to one, irradiation plus chemotherapy to the second and no treatment to the third. In 4 who were not operated, one died without treatment, two accepted chemotherapy and the fourth was treated with irradiation plus chemotherapy. Only two (5%) of these 40 patients had history of exposure to asbestos. The pre- and intra-operative diagnostic conformity rate was 50%. Ten patients were lost from follow-up. The longest survival was twelve years and one month. The authors sum-up their 31-year (1963-1994) experience of this disease and discuss the occupational factors in etiology, clinical diagnosis, treatment options and the significance of pathological types on prognosis of pleural mesothelioma.}, } @article {pmid8678594, year = {1996}, author = {Pellice Vilalta, C and Cosme Giménez, M and Casalots Serramia, J}, title = {[Neoplasms of the tunica of the testis. Report of 5 cases (3 mesothelial tumors and 2 fibrous pseudo-tumors)].}, journal = {Archivos espanoles de urologia}, volume = {49}, number = {1}, pages = {12-16}, pmid = {8678594}, issn = {0004-0614}, mesh = {Aged ; Diagnosis, Differential ; Humans ; Male ; Mesothelioma/*pathology ; Middle Aged ; Testicular Neoplasms/*pathology ; }, abstract = {OBJECTIVES: The problems arising from tumors of the tunica vaginalis testis are reviewed and the differential diagnosis of this uncommon tumor type is discussed.

MATERIAL AND METHODS: Five cases of benign tumor of the tunica vaginalis testis that had been incidentally discovered during hydrocelectomy are described. The patients were evaluated two and five years postoperatively, with no evidence of recurrence or presence of tumor at other sites of the serosa.

RESULTS: The tumors did not compromise the gonad and were treated by simple excision of the hydrocele sac.

CONCLUSIONS: The association of this condition with hydroceles is underscored. The true incidence of exposure to asbestos in the pathogenesis of this tumor type cannot be elucidated from the cases described herein or those in the literature.}, } @article {pmid8657007, year = {1996}, author = {Krajewska, B and Lutz, W and Piłacik, B}, title = {[Exposure to asbestos and levels of selected tumor biomarkers].}, journal = {Medycyna pracy}, volume = {47}, number = {2}, pages = {89-96}, pmid = {8657007}, issn = {0465-5893}, mesh = {Adult ; Asbestos/*adverse effects ; Biomarkers, Tumor/*analysis ; Carcinoembryonic Antigen/*analysis ; *Environmental Monitoring ; Humans ; *Occupational Exposure ; Peptides/*analysis ; Risk Factors ; Tissue Polypeptide Antigen ; }, abstract = {Occupational exposure to asbestos, a recognised carcinogen, poses a risk for such diseases as asbestosis, lung cancer and mesothelioma. It is thought that asbestos fibres may damage microphages which undergo neoplastic transformation as well as fibroblast, while partial phagocytosis may generate free oxygenic radicals which induce cellular peroxidase and damage macromolecules. A search for cellular changes or changes in cellular metabolism products, present in biological fluids, in order to detect early stages of a neoplastic process is an important factor in the prophylaxis of workers exposed to asbestos. Neoplastic biomarkers such as tissue polypeptide antigen (TPA) or carcinoembryonic antigen (CEA) are now used for this purpose. The aim of the work was to identify workers exposed to asbestos in the population, especially high risk groups neoplastic diseases and to evaluate the usefulness of TPA and CEA determinations. The study covered a group of asbestos exposed workers (n = 4000 and the control group of workers (n = 135) nonexposed to any toxic factor at work. Age, exposure time, smoking habits and workpost characteristics were taken into consideration in the analysis of the results. It was revealed that in 38 persons exposed to asbestos, TPA values were above the concentration limit set on the basis of studies carried out in the control group, and elevated CEA values applied to 13 persons. Significant differences between groups under study were found in the proportion of pathological TPA values. Such a relationship was not observed in regard to CEA values. In the exposed group the results also indicated an evident effect of age and exposure time on the number of persons with TPA values above concentration limit. There is a growing tendency in those changes but only in regard to TPA values. The effect of smoking on the frequency of pathological TPA values was also clear-cut in workers exposed to asbestos. Taking into account three types of employment: blue collar workers, white collar workers and other personnel, the analysis indicated significant differences in TPA values between blue collar workers and other personnel; and between white collar workers and other personnel. This means a similar percentage of pathological TPA values in the group of blue collar and white collar workers. The study carried out allowed to identify persons exposed to asbestos who should be covered with targeted medical care. They also proved that TPA biomarker is better than CEA one for this kind of studies.}, } @article {pmid8656999, year = {1996}, author = {Woźniak, H and Wiecek, E and Bielichowska-Cybula, G}, title = {[Exposure to dust mixtures containing free crystalline silica and mineral fibers].}, journal = {Medycyna pracy}, volume = {47}, number = {2}, pages = {151-157}, pmid = {8656999}, issn = {0465-5893}, mesh = {Dust/adverse effects/*analysis ; *Environmental Monitoring ; Humans ; Maximum Allowable Concentration ; Mineral Fibers/adverse effects/*analysis ; Mining ; Neoplasms/chemically induced/prevention & control ; *Occupational Exposure ; Poland ; Risk ; Silicon Dioxide/adverse effects/*analysis ; }, abstract = {Exposure to dust mixture containing at the same time respirable mineral fibres and free crystalline silica may occur in Poland in mines and in the Lower Silesia plants processing mineral raw materials as well as in all plants which use asbestos products and MMMF. Workposts where thermal insulation is exchange with possible phase transformations during operations under conditions of high temperature, expose particularly complex problems. In the work environment of this kind, dust concentration of free crystalline silica becomes important but not sufficient criterion for evaluating working conditions and it may be misleading. A range of studies indispensable for the proper evaluation of exposure to dust, covering together with measurement of dust and SiO2 concentrations, determination of the mineral composition of dust, was developed. It was also found that the acceptable level of risk for neoplastic disease, namely 10(-3) can be attained in the work environment only if the concentration ranges from 0.05 to 0.1 f/cm3, that is equal to 20% of MAC value which is now binding in Poland. Cancer risk (lung cancer and mesothelioma jointly) during a 20-year exposure to concentrations equal to present MAC values should be estimated as about 10(-2) what indicates that risk is too high and it is necessary to diminish MAC values for asbestos dust.}, } @article {pmid8610021, year = {1996}, author = {Mirabella, F}, title = {[Peritoneal mesothelioma and abdominal hernias].}, journal = {Minerva medica}, volume = {87}, number = {1-2}, pages = {21-24}, pmid = {8610021}, issn = {0026-4806}, mesh = {Female ; Hernia, Inguinal/etiology/pathology ; Hernia, Ventral/etiology/*pathology ; Humans ; Male ; Mesothelioma/complications/*pathology ; Peritoneal Neoplasms/complications/*pathology ; }, abstract = {In a review of 720 cases of peritoneal mesothelioma described in Medical Literature, there have been 361 patients for whom the diagnosis has been confirmed by necropsy, 294 by bioptic laparotomy and another 65, where there is no precise information on the method of histopathological diagnosis. Exposure to asbestos can be observed in 55% of the cases studied from the 1960's onwards. As for pathogenesis, amongst other irritant stimuli, it is noteworthy that abdominal hernias provoke mild but chronic reactions on peritoneal serosa. These hernias are to be found in at least 40 of the subjects affected by peritoneal mesothelioma. Reported sites: Inguinal in 28 cases; umbilical in 3 cases; diaphragmatic hiatus in 5 cases; in one case, the site has not been stated. In many cases, hernias may occur as the result of an increase in the endoabdominal pressure caused by ascites or they can be symptomatic of a metastasis of a peritoneal mesothelioma which has spread in a pre-established hernial sac; there are, however, clear examples of primitive, malignant, mesothelial neoplasia of the hernial sac, which can spread throughout the peritoneal cavity months or even years later.}, } @article {pmid8576480, year = {1996}, author = {Raizon, A and Schwartz, A and Hix, W and Rockoff, SD}, title = {Calcification as a sign of sarcomatous degeneration of malignant pleural mesotheliomas: a new CT finding.}, journal = {Journal of computer assisted tomography}, volume = {20}, number = {1}, pages = {42-44}, doi = {10.1097/00004728-199601000-00009}, pmid = {8576480}, issn = {0363-8715}, mesh = {Aged ; Asbestos/adverse effects ; Calcinosis/*diagnostic imaging ; Humans ; Male ; Mesothelioma/*diagnostic imaging/pathology ; Neoplasms, Multiple Primary/*diagnostic imaging/pathology ; Occupational Diseases/diagnostic imaging ; Occupational Exposure ; Osteosarcoma/*diagnostic imaging/pathology ; Pleural Effusion/diagnostic imaging ; Pleural Neoplasms/*diagnostic imaging/pathology ; Radiographic Image Enhancement ; *Tomography, X-Ray Computed ; }, abstract = {We present two cases demonstrating, on CT examination, heavily calcified mass lesions associated with malignant pleural mesothelioma in workers occupationally exposed to asbestos. These masses proved to be osteogenic sarcomatous degeneration within mesotheliomas. The observation of dense calcification within a pleural mass should raise a suspicion of osteosarcomatous degeneration if it is seen in conjunction with other classic signs of malignant pleural mesothelioma.}, } @article {pmid8542156, year = {1996}, author = {Boutin, C and Dumortier, P and Rey, F and Viallat, JR and De Vuyst, P}, title = {Black spots concentrate oncogenic asbestos fibers in the parietal pleura. Thoracoscopic and mineralogic study.}, journal = {American journal of respiratory and critical care medicine}, volume = {153}, number = {1}, pages = {444-449}, doi = {10.1164/ajrccm.153.1.8542156}, pmid = {8542156}, issn = {1073-449X}, mesh = {Adenocarcinoma/*pathology ; Adult ; Aged ; Aged, 80 and over ; *Asbestos ; Asbestos, Amphibole ; Asbestos, Serpentine ; Asbestosis/*pathology ; Female ; Humans ; Lung/pathology ; Lung Neoplasms/pathology ; Male ; Mesothelioma/*pathology ; Microscopy, Electron, Scanning ; Middle Aged ; Mineral Fibers ; Occupations ; Pleura/*pathology ; Pleural Neoplasms/*pathology ; Thoracoscopy ; }, abstract = {Epidemiologic and pathologic data demonstrate that malignant mesothelioma occurs preferentially after exposure to long amphibole asbestos fibers. However, mineralogic studies have rarely detected such fibers in the parietal pleura. We hypothesized that the distribution of asbestos fibers in the pleura was heterogeneous and that they might concentrate in certain areas, as does coal dust in patients showing anthracotic "black spots" of the parietal pleura during thoracoscopy. We collected thoracoscopic biopsy samples from these black spots and from normal areas of the parietal pleura and lung from 14 subjects (eight with and six without asbestos exposure). Asbestos content was determined by transmission electron microscopy. In exposed subjects, mean fiber concentrations were 12.4 +/- 9.8 x 10(6) fibers/g of dry tissue in lung, 4.1 +/- 1.9 in black spots, and 0.5 +/- 0.2 in normal pleura. In unexposed patients, concentrations were 0, 0.3 +/- 0.1, and 0, respectively. Amphiboles outnumbered chrysotile in all samples. A total of 22.5% of fibers were > or = 5 microns in length in black spots. A histologic similarity of these black spots with milky spots is suggested by conventional and electron microscopy. We conclude that the distribution of asbestos fibers is heterogeneous in the parietal pleura. Indeed, the fibers concentrate in black spots, where they can reach high concentrations. These findings could explain why the parietal pleura is the target organ for mesothelioma and plaques.}, } @article {pmid8545879, year = {1995}, author = {Penn, I}, title = {Sarcomas in organ allograft recipients.}, journal = {Transplantation}, volume = {60}, number = {12}, pages = {1485-1491}, doi = {10.1097/00007890-199560120-00020}, pmid = {8545879}, issn = {0041-1337}, mesh = {Humans ; Organ Transplantation/*adverse effects ; Racial Groups ; Registries ; Sarcoma/ethnology/*etiology/physiopathology ; }, abstract = {In a review of 8724 de novo malignancies that occurred in 8191 organ allograft recipients sarcomas were 7.4% of cancers. Kaposi's sarcoma (KS) made up 5.7%, and other sarcomas (OS) 1.7% a much higher proportion than in the general population. KS was most common in Arab, black, Italian, Jewish, or Greek patients. In 60% of patients with KS the lesions were confined to the skin and/or oropharynx while 40% involved internal organs and/or lymph nodes. Complete remissions following various treatments occurred in 53% of the former group and 27% of the latter. In both groups 32% and 60% of remissions, respectively, occurred when the only treatment was reduction or cessation of immunosuppressive therapy. However, this treatment caused impaired function or allograft loss from rejection in 22 of 34 kidney recipients. Recurrent KS occurred in 5% of patients in remission when immunosuppressive therapy was resumed. Nine of 114 patients (8%) tested for human immunodeficiency virus were positive. Most OS arose in internal organs or soft tissues. The major types were fibrous histiocytoma (20 patients), leiomyosarcoma (15), fibrosarcoma (12), rhabdomyosarcoma (9), hemangiosarcoma (8), undifferentiated sarcoma (7) and mesothelioma (6). Several unusual features were noted. Remarkably, 10 of 105 (10%) sarcomas occurred adjacent to or in a renal (6) or hepatic (4) allograft. Leiomyosarcomas are rare in children, yet 5 of 15 (33%) occurred in pediatric patients. Three hemangiosarcomas occurred in forearms at sites of arteriovenous fistulas used for pretransplant hemodialysis access. One leiomyosarcoma and one fibrosarcoma occurred in previously irradiated areas. One patient with mesothelioma had a history of asbestos exposure and two others had possible exposure.}, } @article {pmid8834957, year = {1995}, author = {Ross, D and McDonald, JC}, title = {Occupational and geographical factors in the epidemiology of malignant mesothelioma.}, journal = {Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace}, volume = {50}, number = {6}, pages = {459-463}, pmid = {8834957}, issn = {1122-0643}, mesh = {Adult ; Asbestos/*adverse effects ; Female ; Humans ; Incidence ; Lung Neoplasms/*epidemiology/etiology ; Male ; Mesothelioma/*epidemiology/etiology ; Occupational Diseases/*epidemiology/etiology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*epidemiology/etiology ; Risk Factors ; Sex Factors ; Time Factors ; }, abstract = {In most industrialised countries mortality from malignant mesothelioma has risen steeply since about 1950 and is likely to go on doing so well into the next century. This increase, which has lagged behind the level of asbestos use by some 30 or more years, is most evident in men but less clear in women. Amphibole asbestos fibre types, crocidolite in particular, carry the greatest risk and chrysotile the least. Studies in chrysotile miners and millers, in whom the overall frequency of mesothelioma is low suggest the risk is mainly determined by the presence of contamination with amphibole fibres in the tremolite series. There is wide variation in mesothelioma incidence geographically and occupationally. Regions with the highest rates are those where crocidolite is mined; within countries, dockyard areas are most affected, probably because of amphibole use for insulation in naval ships. Occupations at high risk, apart from crocidolite miners and millers, include shipyard and insulation workers and those employed in construction trades. Data on exposure-response are scanty although occupational cohort studies suggest that risk is related to both duration and intensity of exposure. More specific confirmation of an exposure-response relationship has been obtained from lung fibre analysis in a limited number of case-referent studies.}, } @article {pmid8666112, year = {1995}, author = {De Vuyst, P and Dumortier, P and Swaen, GM and Pairon, JC and Brochard, P}, title = {Respiratory health effects of man-made vitreous (mineral) fibres.}, journal = {The European respiratory journal}, volume = {8}, number = {12}, pages = {2149-2173}, doi = {10.1183/09031936.95.08122149}, pmid = {8666112}, issn = {0903-1936}, mesh = {Air Pollutants, Occupational/*toxicity ; Animals ; Humans ; Lung Diseases/diagnosis/*etiology ; Lung Neoplasms/diagnosis/etiology/mortality ; Mesothelioma/diagnosis/etiology/mortality ; Mineral Fibers/analysis/classification/*toxicity ; Occupational Diseases/etiology ; Pleural Diseases/diagnosis/etiology ; Pneumoconiosis/diagnosis/etiology ; Smoking ; }, abstract = {The group of man-made mineral or vitreous fibres (MMMFs or MMVFs) includes glass wool, rock wool, slag wool, glass filaments and microfibres, and refractory ceramic fibres (RCFs). Experimental observations have provided evidence that some types of MMVF are bioactive under certain conditions. The critical role of size parameters has been demonstrated in cellular and animal experiments, when intact fibres are in direct contact with the target cells. It is, however, difficult to extrapolate the results from these studies to humans since they bypass inhalation, deposition, clearance and translocation mechanisms. Inhalation studies are more realistic, but show differences between animal species regarding their sensibility to tumour induction by fibres. Fibre biopersistence is an important factor, as suggested by recent inhalation studies, which demonstrate positive results with RCF for fibrosis, lung tumours and mesothelioma. There is no firm evidence that exposure to glass-, rock- and slag wool is associated with lung fibrosis, pleural lesions, or nonspecific respiratory disease in humans. Exposure to RCF could enhance the effects of smoking in causing airways obstruction. An elevated standard mortality ratio for lung cancer has been demonstrated in cohorts of workers exposed to MMVF, especially in the early technological phase of mineral (rock slag) wool production. During that period, several carcinogenic agents (arsenic, asbestos, polycyclic aromatic hydrocarbons (PAH)) were also present at the workplace and quantitative data about smoking and fibre levels are lacking. It is not possible from these data to determine whether the risk of lung cancer is due to the MMVFs themselves. No increased risk of mesothelioma has been demonstrated in the cohorts of workers exposed to glass-, slag- or rock wool. There are in fact insufficient epidemiological data available concerning neoplastic diseases in RCF production workers because of the small size of the workforce and the relatively recent industrial production.}, } @article {pmid8635025, year = {1995}, author = {Shin, DM and Fossella, FV and Umsawasdi, T and Murphy, WK and Chasen, MH and Walsh, G and Komaki, R and McMurtrey, MJ and Hong, WK}, title = {Prospective study of combination chemotherapy with cyclophosphamide, doxorubicin, and cisplatin for unresectable or metastatic malignant pleural mesothelioma.}, journal = {Cancer}, volume = {76}, number = {11}, pages = {2230-2236}, doi = {10.1002/1097-0142(19951201)76:11<2230::aid-cncr2820761108>3.0.co;2-2}, pmid = {8635025}, issn = {0008-543X}, mesh = {Adult ; Aged ; Agranulocytosis/chemically induced ; Antibiotics, Antineoplastic/*administration & dosage/adverse effects ; Antineoplastic Agents/*administration & dosage/adverse effects ; Antineoplastic Agents, Alkylating/*administration & dosage/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage/adverse effects/*therapeutic use ; Cisplatin/*administration & dosage/adverse effects ; Cyclophosphamide/*administration & dosage/adverse effects ; Disease Progression ; Disease-Free Survival ; Doxorubicin/*administration & dosage/adverse effects ; Drug Administration Schedule ; Female ; Fever/chemically induced ; Humans ; Male ; Mesothelioma/*drug therapy/secondary ; Middle Aged ; Nausea/chemically induced ; Neutropenia/chemically induced ; Pleural Neoplasms/*drug therapy ; Prospective Studies ; Remission Induction ; Survival Rate ; Vomiting/chemically induced ; }, abstract = {BACKGROUND: This study was designed to determine the efficacy and side effects of a combination of cyclophosphamide (C), doxorubicin (D), and cisplatin (P) in patients with inoperable, unresectable, or metastatic malignant pleural mesothelioma.

METHODS: Twenty-three patients with unresectable or metastatic malignant pleural mesothelioma were entered onto the study. The median age was 62 years (range, 42-74 years); there were 20 males and 3 females; the median performance status was 1 (Zubrod's scale). The histologic types included epithelial (14 patients), sarcomatoid (4 patients), unclassified (4 patients), and mixed type (1 patient). Twenty patients were known to have been exposed to asbestos and 3 were not. All patients were treated with the following starting dose of chemotherapy: a cycle comprised of C, 500 mg/m2 intravenously, day 1; D, 50 mg/m2 intravenously, day 1; and P, 80 mg/m2 intravenously, day 1 every 3 weeks. The cisplatin dose was reduced to 50 mg/m2 for the subsequent courses. For the assessment of tumor response, all patients had computed tomography scans of the chest after each three cycles of chemotherapy.

RESULTS: Overall, 7 of 23 patients (30%) had partial responses (durations of responses [weeks]: 158+, 91+, 70+, 41+, 40, 39, 25), three had minor responses, and 14 had stable or progressive disease. One partial responder later underwent surgical resection and no viable tumors cells were found in the pathologic specimen. All patients have stopped treatment, and eight are still alive. The most common side effect was granulocytopenia (grade 4, 52%; grade 3, 17%). Other hematologic side effects were modest. Nonhematologic side effects included mild to moderate nausea and vomiting, neutropenic fever (three patients), peripheral neuropathy (one patient), and congestive heart failure (one patient). The overall median duration of survival was 60 weeks.

CONCLUSION: Combination chemotherapy with CDP was well tolerated and had significant activity against unresectable or metastatic malignant pleural mesothelioma. The median duration of responses was 60 weeks; however, the survival rate was far from satisfactory. Continued development of new approaches including the biologic understanding of tumor development and testing new agents is warranted.}, } @article {pmid8522310, year = {1995}, author = {Peralta Soler, A and Knudsen, KA and Jaurand, MC and Johnson, KR and Wheelock, MJ and Klein-Szanto, AJ and Salazar, H}, title = {The differential expression of N-cadherin and E-cadherin distinguishes pleural mesotheliomas from lung adenocarcinomas.}, journal = {Human pathology}, volume = {26}, number = {12}, pages = {1363-1369}, doi = {10.1016/0046-8177(95)90302-x}, pmid = {8522310}, issn = {0046-8177}, support = {GM 51188/GM/NIGMS NIH HHS/United States ; }, mesh = {Adenocarcinoma/chemistry/*pathology ; Antibodies, Monoclonal/chemistry ; Cadherins/*immunology ; Cross Reactions ; Cytoskeletal Proteins/immunology ; Diagnosis, Differential ; Humans ; Lung Neoplasms/chemistry/*pathology ; Mesothelioma/chemistry/*pathology ; Pleural Neoplasms/chemistry/*pathology ; *Trans-Activators ; alpha Catenin ; beta Catenin ; }, abstract = {Malignant mesotheliomas are highly aggressive tumors that develop most frequently in the pleura of patients chronically exposed to asbestos. The distinction between malignant mesotheliomas and tumors of epithelial origin, particularly peripheral lung adenocarcinoma, can be difficult despite the use of immunocytochemical markers and other diagnostic tools. During embryonic development the cadherin cell-cell adhesion molecules participate in the segregation of cells into different tissues. As a result of complex mechanisms of tissue selectivity, N-cadherin is expressed by the developing pleural mesothelial cells and E-cadherin is expressed by the epithelial cells of the lung. Thus, we postulated that N-cadherin could be used as a marker of mesothelial cells and mesothelial tumors, in contrast to adenocarcinomas of the lung that are tumors of epithelial origin. We studied the expression of N-cadherin, E-cadherin and two cadherin-associated proteins, alpha-catenin and beta-catenin, in 19 pleural mesotheliomas, 16 lung adenocarcinomas and in 2 mesothelioma cell lines using specific monoclonal antibodies and immunohistochemical methods. Our results show that all mesotheliomas express high levels of N-cadherin, regardless of their histological type, in contrast to lung adenocarcinomas which expressed E-cadherin but no N-cadherin. The cadherin-associated proteins, alpha-catenin and beta-catenin, were present in both mesotheliomas and adenocarcinomas. Our results show that pleural mesotheliomas can be distinguished from lung adenocarcinomas based on the differential expression of N-cadherin and E-cadherin, using specific monoclonal antibodies and immunocytochemistry.}, } @article {pmid7479897, year = {1995}, author = {Bianchi, AB and Mitsunaga, SI and Cheng, JQ and Klein, WM and Jhanwar, SC and Seizinger, B and Kley, N and Klein-Szanto, AJ and Testa, JR}, title = {High frequency of inactivating mutations in the neurofibromatosis type 2 gene (NF2) in primary malignant mesotheliomas.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {92}, number = {24}, pages = {10854-10858}, pmid = {7479897}, issn = {0027-8424}, support = {CA-06927/CA/NCI NIH HHS/United States ; CA-45745/CA/NCI NIH HHS/United States ; }, mesh = {Base Sequence ; Carrier Proteins/genetics ; Chromosomes, Human, Pair 22 ; Cyclin-Dependent Kinase Inhibitor p16 ; *Genes, Neurofibromatosis 2 ; Humans ; Mesothelioma/*genetics ; Molecular Sequence Data ; Pleural Neoplasms/*genetics ; Point Mutation ; Polymorphism, Single-Stranded Conformational ; Sequence Deletion ; }, abstract = {Malignant mesotheliomas (MMs) are aggressive tumors that develop most frequently in the pleura of patients exposed to asbestos. In contrast to many other cancers, relatively few molecular alterations have been described in MMs. The most frequent numerical cytogenetic abnormality in MMs is loss of chromosome 22. The neurofibromatosis type 2 gene (NF2) is a tumor suppressor gene assigned to chromosome 22q which plays an important role in the development of familial and spontaneous tumors of neuroectodermal origin. Although MMs have a different histogenic derivation, the frequent abnormalities of chromosome 22 warranted an investigation of the NF2 gene in these tumors. Both cDNAs from 15 MM cell lines and genomic DNAs from 7 matched primary tumors were analyzed for mutations within the NF2 coding region. NF2 mutations predicting either interstitial in-frame deletions or truncation of the NF2-encoded protein (merlin) were detected in eight cell lines (53%), six of which were confirmed in primary tumor DNAs. In two samples that showed NF2 gene transcript alterations, no genomic DNA mutations were detected, suggesting that aberrant splicing may constitute an additional mechanism for merlin inactivation. These findings implicate NF2 in the oncogenesis of primary MMs and provide evidence that this gene can be involved in the development of tumors other than nervous system neoplasms characteristic of the NF2 disorder. In addition, unlike NF2-related tumors, MM derives from the mesoderm; malignancies of this origin have not previously been associated with frequent alterations of the NF2 gene.}, } @article {pmid7479890, year = {1995}, author = {Knudson, A}, title = {Asbestos and mesothelioma: genetic lessons from a tragedy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {92}, number = {24}, pages = {10819-10820}, pmid = {7479890}, issn = {0027-8424}, mesh = {Asbestosis/*genetics ; Cell Division ; Chromosome Aberrations/*pathology ; Chromosome Disorders ; Genes, Neurofibromatosis 2 ; Humans ; Mesothelioma/*genetics ; Peritoneal Neoplasms/*genetics ; Pleural Neoplasms/*genetics ; }, } @article {pmid8583723, year = {1995}, author = {Matsuzawa, K and Hamada, K and Tokuyama, T and Yoneda, T and Narita, N and Sawabata, A and Iioka, S and Imai, S and Sakaguchi, Y and Miyataka, K}, title = {[A case of desmoplastic malignant mesothelioma].}, journal = {Nihon Kyobu Shikkan Gakkai zasshi}, volume = {33}, number = {11}, pages = {1288-1292}, pmid = {8583723}, issn = {0301-1542}, mesh = {Adult ; Asbestos/adverse effects ; Humans ; Lung Neoplasms/etiology/*pathology ; Male ; Mesothelioma/etiology/*pathology ; Occupational Diseases/etiology/*pathology ; *Occupational Exposure ; }, abstract = {A 43-year-old man was admitted to Nara Medical University Hospital because of right-sided chest pain. Computed tomographic examination revealed a right pleural effusion and diffuse pleural thickening. Malignant mesothelioma was diagnosed from the results of a percutaneous pleural biopsy, and the patient then underwent right pleuro-pneumonectomy. The resected specimen was examined by light and electron microscopy, which revealed scattered sarcoma-like malignant cells with some epithelial differentiation, in abundant extracellular collagen with storiform derangement. Therefore, desmoplastic malignant mesothelioma (mixed type) was diagnosed. This is a rare histological subgroup of malignant mesotheliomas. The patient died 2 months after the operation, due to multiple and rapidly growing metastases. After lung tissue was dissolved, ferruginous (asbestos) bodies were counted, and the results were consistent with occupational exposure to asbestos (413 asbestos bodies per 5 g of lung tissue).}, } @article {pmid8535500, year = {1995}, author = {Coggon, D and Inskip, H and Winter, P and Pannett, B}, title = {Differences in occupational mortality from pleural cancer, peritoneal cancer, and asbestosis.}, journal = {Occupational and environmental medicine}, volume = {52}, number = {11}, pages = {775-777}, pmid = {8535500}, issn = {1351-0711}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Asbestosis/*mortality ; Carcinogens/adverse effects ; England/epidemiology ; Humans ; Male ; Mesothelioma/etiology/*mortality ; Middle Aged ; Occupational Exposure/adverse effects/*statistics & numerical data ; Peritoneal Neoplasms/etiology/*mortality ; Pleural Neoplasms/etiology/*mortality ; Prevalence ; Wales/epidemiology ; }, abstract = {OBJECTIVE: To assess whether the increased risk of disease related to asbestos in occupations from the construction and engineering industries applies equally to pleural cancer, peritoneal cancer, and asbestosis.

METHODS: Analysis was based on deaths among men aged 20-74 in England and Wales during 1979-80 and 1982-90. (n = 1,656,096). Information about cause of death and the last full time occupation of decedents was derived from death certificates. Proportional mortality ratios (PMRs) by occupation were calculated for each of pleural cancer, peritoneal cancer, and asbestosis.

RESULTS: Altogether, 2848 deaths were attributed to cancer of the pleura, 362 to cancer of the peritoneum, and 281 to asbestosis. When occupations were ranked according to PMRs from these diseases, striking differences were found. The category of construction workers which included laggers had the highest mortality from peritoneal cancer (PMR 990, 64 deaths), but a PMR of only 160 (77 deaths) for pleural cancer. In contrast, several occupations with much higher mortality from pleural tumours had no excess of peritoneal cancer. PMRs for asbestosis related more closely to those for peritoneal than pleural cancer.

CONCLUSIONS: These findings suggest that the exposure-response relations for diseases related to asbestos are not all linear, and that risks of pleural mesothelioma may be underestimated by simple extrapolation from observations in cohorts with heavy exposure.}, } @article {pmid8520817, year = {1995}, author = {Mesía, R and Pallares, C and Mendoza, L and Bellet, M and Vega, M and León, C and López López, JJ}, title = {[Malignant pleural mesothelioma: clinical characteristics, prognostic factors and treatment].}, journal = {Archivos de bronconeumologia}, volume = {31}, number = {9}, pages = {455-459}, doi = {10.1016/s0300-2896(15)30865-6}, pmid = {8520817}, issn = {0300-2896}, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Data Interpretation, Statistical ; Female ; Humans ; Karnofsky Performance Status ; Male ; Mesothelioma/*diagnosis/mortality/therapy ; Middle Aged ; Palliative Care ; Pleural Neoplasms/*diagnosis/mortality/therapy ; Prognosis ; Time Factors ; }, abstract = {Malignant pleural mesothelioma soon leads to death no matter what type of treatment is provided. We discuss the clinical signs, prognostic factors and treatment given in 41 cases managed over the past 13 years in our oncology department. 32% had been exposed to asbestos, 61% were 60 years old or younger, 71% had a Karnofsky's index > or = 80% and 63% were stage I (Butchart). The first symptom leading to diagnosis was pain in 66% and mean time between first symptom and diagnosis was 3 months. Thirty patients never experienced full remission of disease: 15 were treated with palliative chemotherapy (CHT), 1 with palliative radiotherapy (RT), 5 with partial pleurectomy (PP) plus RT and/or CHT. Nine were given symptomatic treatment only. Only 11 (27%) patients experienced full remission after treatment: 7 had had extrapleural pneumonectomy, 2 had been given CHT and RT series and 4 had undergone PP with or without RT and/or CHT follow-up. Only 3 of these patients were still alive with no relapse more than 1 year later. Mean survival was 8 months. Univariate analysis revealed that the prognostic factors influencing survival were age and Karnofsky's index. Patients initially treated with surgery had a higher rate of survival. In conclusion, only Karnofsky's index and age were prognostic factors in our series. The better survival of patients initially treated surgically is probably related to prior screening.}, } @article {pmid7586195, year = {1995}, author = {Yegles, M and Janson, X and Dong, HY and Renier, A and Jaurand, MC}, title = {Role of fibre characteristics on cytotoxicity and induction of anaphase/telophase aberrations in rat pleural mesothelial cells in vitro: correlations with in vivo animal findings.}, journal = {Carcinogenesis}, volume = {16}, number = {11}, pages = {2751-2758}, doi = {10.1093/carcin/16.11.2751}, pmid = {7586195}, issn = {0143-3334}, mesh = {Anaphase ; Aneuploidy ; Animals ; Asbestos/*toxicity ; Asbestos, Amosite/toxicity ; Asbestos, Crocidolite/toxicity ; Cell Survival ; Cells, Cultured ; *Chromosome Aberrations ; Epithelium/ultrastructure ; Pleura/*ultrastructure ; Rats ; Telophase ; }, abstract = {Thirteen samples of natural fibres and five samples of man-made fibres (MMF) were tested to determine their cytotoxicity and ability to produce chromosome missegregation in cultures in rat pleural mesothelial cells (RPMC). The natural samples included attapulgite, two amphiboles (amosite and crocidolite); seven consisted of chrysotile from various origins and three were obtained after chemical treatment of chrysotile. MMF included three refractory ceramic fibres (RCF) and two vitreous fibres (MMVF). All fibre samples were characterized by electron microscopic measurement of the fibre dimensions. Cytotoxicity was assayed on the basis of determination of mitochondrial integrity and chromosome missegregation by light microscopy examination of anaphases/telophases. The carcinogenic potency of 10 natural samples has been previously investigated using intrapleural inoculation in rats. It was therefore possible to establish correlations between in vitro and in vivo data obtained with the same set of samples. The various samples of chrysotile produced different in vitro effects, in agreement with the dispersion of response also observed in vivo. Cytotoxicity appears to be dependent on both fibre length and fibre diameter, as the longest or thickest fibres were the most toxic. The production of abnormal anaphases/telophases appears to depend on the presence of fibres of selected size, such as those previously defined by Stanton et al. (L > 8 micrograms; D < or = 0.25 microns); a threshold values was determined below which no abnormal anaphases/telophases were detected. This non-observable effect level was estimated to be 2.5 x 10(5) 'Stanton' fibres per cm2. There was no correlation between cytotoxicity and mesothelioma induction; in contrast, a correlation was found between the ability of a sample to produce chromosome missegregation in vitro and mesothelioma in vivo.}, } @article {pmid7565276, year = {1995}, author = {Kilpatrick, DJ}, title = {Mesothelioma: is asbestos exposure the only cause?.}, journal = {The Medical journal of Australia}, volume = {163}, number = {7}, pages = {392}, pmid = {7565276}, issn = {0025-729X}, mesh = {Asbestos/*adverse effects ; Environmental Exposure/*adverse effects ; Female ; Humans ; Male ; Mesothelioma/*chemically induced/virology ; }, } @article {pmid9166476, year = {1995}, author = {Penno, MB and Askin, FB and Ma, H and Carbone, M and Vargas, MP and Pass, HI}, title = {High CD44 expression on human mesotheliomas mediates association with hyaluronan.}, journal = {The cancer journal from Scientific American}, volume = {1}, number = {3}, pages = {196-203}, pmid = {9166476}, issn = {1081-4442}, support = {P50 CA058184/CA/NCI NIH HHS/United States ; P50-CA58184/CA/NCI NIH HHS/United States ; }, mesh = {Antibodies, Monoclonal/chemistry/immunology ; Blotting, Western ; Cell Adhesion/physiology ; Cell Line, Tumor ; Humans ; Hyaluronan Receptors/*biosynthesis/immunology ; Hyaluronic Acid/*metabolism ; Immunohistochemistry ; Mesothelioma/immunology/*metabolism/pathology ; Pleural Neoplasms/immunology/*metabolism/pathology ; }, abstract = {PURPOSE: Malignant pleural mesothelioma is a rare malignancy with major environmental implications regarding passive asbestos exposure. We have conducted an immunohistochemical and functional study to address three questions: (1) What is the representation of CD44 on tumor cells as detected by immunohistochemistry? (2) Do cultured cell lines derived from malignant pleural mesothelioma tissue express the same CD44 phenotypes as the original tumors, and can they serve as a model for the study of CD44 in mesotheliomas? (3) What is the functional status of the CD44 expressed on mesotheliomas, with regard to hyaluronan anchorage?

MATERIALS AND METHODS: Thirty-seven samples of pleural mesothelioma were obtained from patients entered on phase I/II protocols conducted in the Surgery Branch of the National Cancer Institute since 1991. The diagnosis was confirmed in all 37 patients by means of a battery of immunohistochemical tests for markers differentiating malignant pleural mesothelioma from adenocarcinoma. Tumor-positive lymph nodes and distant metastases were also examined in six of the patients. Cell lines, established from tumor tissue of six of the patients described above, were used in these experiments. Four (H2596, H2461, H2373, H2452) were derived from primary solid tumors and two (HP-1 and HP-3) were derived from effusions.

RESULTS: Immunohistochemical staining with a monoclonal antibody (H4C4) that recognizes a constant region of human CD44 demonstrated that 34 (92%) of the malignant pleural mesotheliomas examined expressed CD44 on 50% to 100% of their cells. The extent of CD44 expression was apparently related to histologic subtype with the highest expression seen in epithelioid mesotheliomas and the least in sarcomatoid tumors. Tumor cell lines established from the primary tumors or effusions of six of the malignant pleural mesothelioma patients showed high expression of the hematopoietic form of CD44. Four of these cell lines exhibited strong attachment to hyaluronan in an in vitro attachment assay, indicating that their CD44 was functional with respect to hyaluronan anchorage. Hyaluronan attachment was specific in that it could be abolished by preincubation with epitope-specific anti-CD44 antibodies or soluble substrate or by hyaluronidase treatment of attachment surfaces.

CONCLUSIONS: We conclude that CD44 is highly expressed on human mesotheliomas, that cell lines adequately represent tumor expression, and that CD44 mediates association with hyaluronan, a major component of pleural fluid.}, } @article {pmid8713204, year = {1995}, author = {Musk, AW and de Klerk, NH and Eccles, JL and Hansen, J and Shilkin, KB}, title = {Malignant mesothelioma in Pilbara Aborigines.}, journal = {Australian journal of public health}, volume = {19}, number = {5}, pages = {520-522}, doi = {10.1111/j.1753-6405.1995.tb00421.x}, pmid = {8713204}, issn = {1035-7319}, mesh = {Adult ; Aged ; Asbestos, Crocidolite/*adverse effects ; Carcinogens/*adverse effects ; Female ; Humans ; Lung Neoplasms/diagnosis/epidemiology/*ethnology ; Male ; Mesothelioma/diagnosis/epidemiology/*ethnology ; Middle Aged ; Mining ; *Native Hawaiian or Other Pacific Islander ; Occupational Exposure/adverse effects ; Western Australia/epidemiology ; }, abstract = {Malignant mesothelioma occurred in a female Aborigine after environmental exposure to asbestos. All known cases of the disease in Aborigines in Western Australia were reviewed; all occurred in Pilbara residents. Most were exposed while involved in the transport of asbestos from the Wittenoom crocidolite operation. Based on recent estimates of the size of the Aboriginal population in the Pilbara region, their incidence of this disease (250 per million for ages 15 and over) is one of the highest population-based rates recorded.}, } @article {pmid8622811, year = {1995}, author = {Pentimone, F and Moruzzo, D and Siuti, E and del Corso, L}, title = {[Malignant peritoneal mesothelioma: its relation to asbestos].}, journal = {Minerva medica}, volume = {86}, number = {10}, pages = {439-443}, pmid = {8622811}, issn = {0026-4806}, mesh = {Aged ; Asbestos/*adverse effects ; Fatal Outcome ; Humans ; Magnetic Resonance Imaging ; Male ; Mesothelioma/*chemically induced/diagnosis/pathology ; Middle Aged ; Occupational Exposure ; Peritoneal Neoplasms/*chemically induced/diagnosis/pathology ; Tomography, X-Ray Computed ; }, abstract = {Chronic exposure to asbestos can induce malignant peritoneal mesothelioma (PMM) without pulmonary or pleural involvement (PIMM). The localization to the peritoneum depends on the different susceptibility of the two mesotheliums and, perhaps, on the length of asbestos fibers which can facilitate their direct translocation.}, } @article {pmid8526406, year = {1995}, author = {Rossiter, CE and Chase, JR}, title = {Statistical analysis of results of carcinogenicity studies of synthetic vitreous fibres at Research and Consulting Company, Geneva.}, journal = {The Annals of occupational hygiene}, volume = {39}, number = {5}, pages = {759-769}, doi = {10.1016/0003-4878(95)00054-i}, pmid = {8526406}, issn = {0003-4878}, mesh = {Animals ; *Carcinogenicity Tests ; Ceramics ; Cricetinae ; Kaolin ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Mineral Fibers/*toxicity ; Rats ; Rats, Inbred F344 ; }, abstract = {Five inhalation studies of synthetic vitreous fibres have recently investigated experimental tumorigenic responses to four different refractory ceramic fibres (RCF), two fibre glasses, one stone (rock) wool and one slag wool. Except for one RCF, the source materials were typical commercial products. Three studies included positive control groups exposed to chrysotile or crocidolite asbestos. The studies were conducted using state-of-the-art technologies for fibre size separation, fibre lofting and nose-only inhalation exposure. The target average fibre size was 20 microns long by 1 micron diameter. Hamsters exposed to a kaolin RCF yielded a mesothelioma rate of 38%, but no lung cancers. There were no tumours among the chrysotile-exposed hamsters. At the highest dose of 30 mg m-3 in rat studies, the commercial RCF all produced significant numbers of lung tumours, and some mesotheliomas. The fourth RCF, which had been heat-treated to simulate an after-service fibre, did not produce a significant excess of lung cancers, but did produce one mesothelioma. A rat multi-dose experiment with three lower doses of the kaolin RCF yielded one mesothelioma among 379 rats, but no excess of lung tumours. The overall dose-response relation for lung cancer did not appear to be linear, consistent with the possibility of a threshold close to the Maximum Tolerated Dose. No insulation wool (glass, stone or slag) exposure group had a lung tumour rate that differed statistically significantly from the tumour rate for the respective concurrent control groups, sham-exposed to filtered air. There was no significant difference in the total tumour rates between the four insulation wool groups and the control animals, and no significant dose-response relation above the respective sham-exposed control tumour rates. The total lung tumour rates for rats in both chrysotile and crocidolite exposure groups were significantly raised. One animal in each asbestos-exposed group developed a mesothelioma, whereas no air control or insulation wool-exposed animal did so.}, } @article {pmid8526402, year = {1995}, author = {Rödelsperger, K and Woitowitz, HJ}, title = {Airborne fibre concentrations and lung burden compared to the tumour response in rats and humans exposed to asbestos.}, journal = {The Annals of occupational hygiene}, volume = {39}, number = {5}, pages = {715-725}, pmid = {8526402}, issn = {0003-4878}, mesh = {Animals ; *Asbestos ; Asbestos, Serpentine ; Body Burden ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Mineral Fibers ; *Mining ; Occupational Diseases/*etiology ; Occupational Exposure ; Rats ; }, abstract = {The excess risk of tumours exposed to asbestos were previously compared with the results of rat inhalation experiments. It could be demonstrated that humans at the workplace suffer from a tumour risk at fibre concentrations which are 300 times lower than those needed in the rat inhalation model to produce the same risk. However, the estimation of human risk was based on the study of workers at a chrysotile textile factory, whereas animal experimental results were related to exposure to amphiboles. Since for this comparison the risk of cancer due to exposure to amosite or crocidolite fibres at the workplace is of interest, quantitative exposure-response relationships for lung cancer and mesothelioma for the white workforce of South African amosite and crocidolite mines were discussed. On comparing the risk of lung cancer in this study with the risk of lung cancer for chrysotile textile workers, it can be concluded, that the risk of lung cancer and mesothelioma from crocidolite and amosite was higher than in the chrysotile textile factory. It could be also demonstrated, on the basis of a study of the lung burden of mesothelioma cases and of controls, that a significantly increased odds ratio of about 5 was established at amphibole concentrations of between 0.1 and 0.2 f micrograms-1 dry lung (WHO fibres longer than 5 microns from TEM analysis). On the other hand, carcinogenic response was observed at a fibre concentration 6000 times higher in animal inhalation experiments with crocidolite asbestos (SEM analysis of WHO fibres). As a result of these findings, it has been concluded that inhalation studies in rats are not sufficiently sensitive for the detection of hazards and risks to humans exposed to man-made fibres.}, } @article {pmid8526395, year = {1995}, author = {Hesterberg, TW and Miiller, WC and Thevenaz, P and Anderson, R}, title = {Chronic inhalation studies of man-made vitreous fibres: characterization of fibres in the exposure aerosol and lungs.}, journal = {The Annals of occupational hygiene}, volume = {39}, number = {5}, pages = {637-653}, doi = {10.1016/0003-4878(94)00091-e}, pmid = {8526395}, issn = {0003-4878}, mesh = {Aerosols ; Animals ; Cricetinae ; Inflammation ; Lung Neoplasms/*etiology ; Male ; *Mineral Fibers ; Pulmonary Fibrosis/*etiology ; Rats ; Rats, Inbred F344 ; }, abstract = {Inhalation studies were conducted to determine the chronic biological effects in rodents of respirable fractions of different man-made vitreous fibres (MMVFs), including refractory ceramic fibre (RCF), fibrous glass, rock (stone) wool and slag wool. Animals were exposed nose-only, 6 h per day, 5 days per week, for 18 months (hamsters) or 24 months (rats). Exposure to 10 mg m-3 of crocidolite or chrysotile asbestos induced pulmonary fibrosis, lung tumours and mesothelioma in rats, thus validating the inhalation model with known human carcinogenic fibres. Exposure of rats to 30 mg m-3 of refractory ceramic fibres (RCF) also resulted in pulmonary fibrosis as well as significant increases in lung tumours and mesothelioma. In hamsters, 30 mg m-3 of RCF induced a 41% incidence of mesotheliomas. Exposure of rats to 30 mg m-3 of fibre glasses (MMVF 10 or 11) or of slag wool (MMVF 22) was associated with an inflammatory response, but no mesotheliomas or significant increase in the lung tumours were observed. Rock wool (stone wool: MMVF 21) at the same exposure level resulted in minimal lung fibrosis, but no mesotheliomas or significant increase in the lung tumours were observed. Fibre numbers (WHO fibres) and dimensions in the aerosols and lungs of exposed animals were comparable in this series of inhalation studies. Differences in lung fibre burdens and lung clearance rates could not explain the differences observed in the toxicologic effects of the MMVFs. These findings indicate that dose, dimension and durability may not be the only determinants of fibre toxicity. Chemical composition and the surface physico-chemical properties of the fibres may also play an important role.}, } @article {pmid7560092, year = {1995}, author = {Boylan, AM and Sanan, DA and Sheppard, D and Broaddus, VC}, title = {Vitronectin enhances internalization of crocidolite asbestos by rabbit pleural mesothelial cells via the integrin alpha v beta 5.}, journal = {The Journal of clinical investigation}, volume = {96}, number = {4}, pages = {1987-2001}, pmid = {7560092}, issn = {0021-9738}, support = {HL-47412/HL/NHLBI NIH HHS/United States ; HL/A-133259/HL/NHLBI NIH HHS/United States ; R01 ESO6331/ES/NIEHS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Asbestos, Crocidolite/*metabolism ; Cells, Cultured ; Epithelium/metabolism ; Fluorescence ; Integrins/*physiology ; Molecular Sequence Data ; Oligopeptides/pharmacology ; Pleura/*metabolism ; Rabbits ; Receptors, Vitronectin/physiology ; Vitronectin/*pharmacology ; }, abstract = {The mechanism by which pleural mesothelial cells, the likely progenitor cells of asbestos-induced mesothelioma, recognize and internalize crocidolite asbestos is unknown. Because incubation of asbestos fibers with serum increases their association with cells, we asked whether a protein coat on asbestos increased internalization of fibers via specific cellular receptors. Coating crocidolite with citronectin, but not with fibronectin or other proteins, increased fiber internalization by rabbit pleural mesothelial cells, as measured by a new technique using fluorescence confocal microscopy. Receptors for vitronectin, alpha v beta 3 and alpha v beta 5, were identified on mesothelial cells. Inhibiting vitronectin receptors by plating cells on a vitronectin substrate or incubating cells with excess soluble vitronectin reduced internalization of vitronectin-coated crocidolite. Inhibition of alpha v beta 5, but not alpha v beta 3, with blocking antibodies similarly reduced internalization. In addition, alpha v beta 5, but not alpha v beta 3, showed immunocytochemical colocalization with fibers. Of biologic relevance, coating crocidolite with serum also increased internalization via alpha v beta 5, an effect dependent on the vitronectin in serum. We conclude that pleural mesothelial cells recognize and internalize vitronectin- and serum-coated asbestos via the integrin alpha v beta 5. Since integrins initiate some of the same signaling pathways as does asbestos, our findings may provide insights into the mechanisms of asbestos-induced biologic effects.}, } @article {pmid7500972, year = {1995}, author = {Frank, AL}, title = {Medical and public health approaches to asbestos disease.}, journal = {The Mount Sinai journal of medicine, New York}, volume = {62}, number = {5}, pages = {401-405}, pmid = {7500972}, issn = {0027-2507}, mesh = {*Asbestosis ; Environmental Exposure ; Humans ; Pneumoconiosis ; Public Health ; Smoking/adverse effects ; }, abstract = {Asbestos is known to cause a wide range of nonmalignant and malignant disease among occupationally and environmentally exposed individuals. Lung cancer and mesothelioma are of special importance. X-rays are evaluated utilizing the ILO classification, and the clinical signs and symptoms of many chronic lung diseases may occur. The fibrous nature of asbestos appears to be important, and fiber size plays a role in carcinogenic outcome. Because of the significant legal and public health implications of exposure, it appears that purposeful obfuscation of asbestos science has taken place. There are also worldwide efforts to shift patterns of use and manufacturing, leading to a wider dissemination of death and disease, especially when coupled with spreading tobacco usage.}, } @article {pmid7565249, year = {1995}, author = {Gun, RT}, title = {Mesothelioma: is asbestos exposure the only cause?.}, journal = {The Medical journal of Australia}, volume = {163}, number = {6}, pages = {334-335}, pmid = {7565249}, issn = {0025-729X}, mesh = {Asbestos/*adverse effects ; Causality ; Humans ; Mesothelioma/*etiology ; }, } @article {pmid8684301, year = {1995}, author = {Mollo, F and Magnani, C}, title = {European multicentric case control study on risk for mesothelioma after non-occupational (domestic and environmental) exposure to asbestos.}, journal = {La Medicina del lavoro}, volume = {86}, number = {5}, pages = {496-500}, pmid = {8684301}, issn = {0025-7818}, mesh = {Asbestos/*adverse effects ; Case-Control Studies ; Environmental Exposure ; Female ; Heart Neoplasms/diagnosis/*etiology/pathology ; Humans ; Male ; Mesothelioma/diagnosis/*etiology/pathology ; Occupational Exposure ; Occupational Health ; Pericardium/pathology ; Pleura/pathology ; Pleural Neoplasms/diagnosis/*etiology/pathology ; Surveys and Questionnaires ; }, abstract = {The paper presents the European multicentric case-control study on risk for mesothelioma after non-occupational (domestic and environmental) exposure to asbestos. The study includes eight centres in seven European countries (Belgium, Denmark, Greece, Italy, Spain, Sweden and Switzerland). It is focused on the measurement of mesothelioma risk in relation to low intensity exposure to asbestos and to exposure to MMMF and other agents. It includes incident cases of pleural malignant mesothelioma (histologically diagnosed and verified) and a random sample of the population.}, } @article {pmid8684300, year = {1995}, author = {Frank, AL}, title = {Asbestos mineralogic analysis as indicator of carcinogenic risk.}, journal = {La Medicina del lavoro}, volume = {86}, number = {5}, pages = {490-495}, pmid = {8684300}, issn = {0025-7818}, mesh = {Asbestos/*adverse effects/*analysis ; Asbestos, Amphibole/adverse effects/analysis ; Asbestos, Serpentine/adverse effects/analysis ; Humans ; Lung/chemistry ; Mesothelioma/*etiology ; Microscopy, Electron ; Microscopy, Electron, Scanning ; Microscopy, Polarization ; Mineral Fibers/*analysis ; Pleura/chemistry ; Risk Factors ; Sputum/chemistry ; X-Ray Diffraction ; }, abstract = {Asbestos fibers can be found in several tissues and fluids, by different techniques, but up to now there is not a standardised approach. Chrysotile seems to be removed from the lung with greater ease than the amphiboles, but it is more frequently found in pleural tissues. Human and animal studies agree in documenting that chrysotile and amphiboles produce mesotheliomas, even if these studies rarely add much to the understanding of mechanisms of asbestos-related diseases. Further of asbestos-related diseases. Further studies are needed with standardized materials and techniques to better understand these mechanisms and to determine which individuals may be at highest risk for the development of disease.}, } @article {pmid8684299, year = {1995}, author = {Pinto, C and Soffritti, M and Maltoni, C}, title = {Ignored occupational risks of asbestos mesotheliomas.}, journal = {La Medicina del lavoro}, volume = {86}, number = {5}, pages = {484-489}, pmid = {8684299}, issn = {0025-7818}, mesh = {Adolescent ; Adult ; Aged ; Asbestos/*adverse effects ; Humans ; Male ; Mesothelioma/*etiology ; Middle Aged ; *Occupational Exposure ; Occupations ; Pleural Neoplasms/*etiology ; Risk Factors ; Time Factors ; }, abstract = {Nine cases of asbestos mesothelioma following usually ignored asbestos exposure were reported. In these cases the asbestos exposure has been traced following a thorough medical inquiry within the hospital. Such a type of inquiry would reduce the number of mesotheliomas due to unknown causes or considered spontaneous. The role of the hospitals as a primary source of epidemiological information is stressed.}, } @article {pmid8684298, year = {1995}, author = {Maltoni, C and Pinto, C and Valenti, D and Carnuccio, R and Amaducci, E and Minardi, F}, title = {Mesotheliomas following exposure to asbestos used in sugar refineries: report of 12 Italian cases.}, journal = {La Medicina del lavoro}, volume = {86}, number = {5}, pages = {478-483}, pmid = {8684298}, issn = {0025-7818}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Female ; *Food-Processing Industry ; Humans ; Italy/epidemiology ; Male ; Mesothelioma/*etiology/mortality/pathology ; Middle Aged ; *Occupational Exposure ; Pleura/pathology ; Pleural Neoplasms/*etiology/mortality/pathology ; Risk Factors ; *Sucrose ; Time Factors ; }, abstract = {Twelve Italian cases of mesothelioma (all the cases but one from the Emilia Romagna Region), following exposure to asbestos used in sugar refinery plants, are reported. Eleven cases arose in workers occupationally exposed, and one in the daughter of an exposed worker, following family contact. Eleven of the cases were pleural and one peritoneal. In the 11 cases following occupational exposure the average latency time was 36.0 (range 23-48) years, and the average age at onset was 63.4 years. In the case which followed family contact, the latency time and the age of the onset were 37 years. This represents the largest series of cases of mesothelioma due to the asbestos present in sugar refinery plants reported to date in the scientific literature. While these cases demonstrate the risk of asbestos mesothelioma in the sugar refinery industry, they in no way give the dimension of the pathological effects of asbestos (and man-made mineral fibres) used in this industry. To assess this risk further research is suggested.}, } @article {pmid8684297, year = {1995}, author = {Maltoni, C and Pinto, C and Carnuccio, R and Valenti, D and Lodi, P and Amaducci, E}, title = {Mesotheliomas following exposure to asbestos used in railroads: 130 Italian cases.}, journal = {La Medicina del lavoro}, volume = {86}, number = {5}, pages = {461-477}, pmid = {8684297}, issn = {0025-7818}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Female ; Heart Neoplasms/*etiology ; Humans ; Italy ; Lung Neoplasms/*etiology ; Male ; Mesothelioma/*etiology ; Middle Aged ; *Occupational Exposure ; Occupations ; Pericardium ; Peritoneal Neoplasms/*etiology ; Pleural Neoplasms/*etiology ; *Railroads ; Risk Factors ; Time Factors ; }, abstract = {The available knowledge on the oncogenic risks of asbestos, the data on the uses of asbestos in railroads, with particular regard to the Italian State Railroads (Ferrovie dello Stato = FS), and the groups at risk due to the exposure to asbestos used in railroads were briefly reviewed. The available data on the pathological effects of such exposure, and particularly on the onset of mesotheliomas among machinists and other railroad workers, were also summarized. One hundred and thirty cases of mesothelioma (122 pleural, 1 pericardial, 6 peritoneal and 1 pleuro-peritoneal), related to the exposure to asbestos used in railroads, observed in various Italian regions, were reported. Fifty-three of these cases (among which 49 reported in the Emilia Romagna Region) were submitted to a detailed study at the Bologna Institute of Oncology. Seventy-seven cases of mesothelioma occurred among occupationally exposed FS workers, in particular machinists; 45 cases occurred among rolling-stock machinists and workers engaged in the repair and demolition of the rails of workshops not belonging to the FS; 3 cases occurred among travelling workers of rolling-stock, not belonging to the FS; and 5 cases were found in family members (1 daughter, 3 wives and 1 sister) of railroad workers. This series of cases, together with similar data from the literature, proves the existence of an actual health risk due to asbestos used in railroads, and indicates its gravity. On the basis of the available data, the following steps are considered necessary: the promotion of systematic epidemiological investigations, the adoption of preventive measures, the performance of medical oncological surveillance, and the automatic compensation for tumours following the exposure to the asbestos used in railroads.}, } @article {pmid8684296, year = {1995}, author = {Frank, AL}, title = {The use of asbestos in Japan and China and malignancy related findings.}, journal = {La Medicina del lavoro}, volume = {86}, number = {5}, pages = {457-460}, pmid = {8684296}, issn = {0025-7818}, mesh = {Animals ; Asbestos/*adverse effects ; Asbestosis/epidemiology/*etiology ; China/epidemiology ; Environmental Exposure ; Female ; Humans ; Japan/epidemiology ; Lung Neoplasms/epidemiology/*etiology ; Male ; Mesothelioma/epidemiology/*etiology ; Occupational Exposure ; Occupations ; Pleural Neoplasms/epidemiology/*etiology ; Research ; Risk Factors ; }, abstract = {Asbestos use in industrialized countries is generally being curtailed, with the exception of Japan which, even if it is not a major producer, is now the world's largest user, and this use is still increasing. On the contrary, China is one of the major producers at world levels. The author refers data from the literature dealing with epidemiological, and also experimental, studies performed in these two countries, which confirm that asbestos produces mesotheliomas in man and laboratory animals. The author underlines the possibility of demonstrating, through epidemiological studies, differences with respect to western countries, possibly related to different life styles and genetic and racial influences, and proposes some categories at risk, for either environmental or occupational reasons, which are particularly interesting for this type of study.}, } @article {pmid8684295, year = {1995}, author = {Richter, ED and Berdugo, M and Laster, R and Westin, JB and Fischbein, A}, title = {Chrysotile and crocidolite asbestos in Israel: uses, exposures and risks.}, journal = {La Medicina del lavoro}, volume = {86}, number = {5}, pages = {449-456}, pmid = {8684295}, issn = {0025-7818}, mesh = {Adolescent ; Adult ; Asbestos, Crocidolite/*adverse effects ; Asbestos, Serpentine/*adverse effects ; Asbestosis/*etiology ; Child ; Environmental Exposure ; Female ; Humans ; Israel/epidemiology ; Lung Neoplasms/epidemiology/*etiology ; Male ; Mesothelioma/epidemiology/*etiology ; Occupational Exposure ; Occupations ; Risk Factors ; Smoking/adverse effects ; }, abstract = {Importation of raw asbestos (90% chrysotile; 10% crocidolite) for manufacture of cement products and other uses, including friction materials and spraying, had dropped to under 3000 tons by 1993 from a peak of 10,000 tons per annum in the late 1970s. Drops in use, manufacture, persons exposed in manufacture and measured exposure levels followed heightened public concern over the carcinogenic effects of asbestos products, despite a relatively high worker exposure standard of 400,000 f/m3. The atypically low ratio of reported deaths from lung cancer compared to mesothelioma in asbestos cement workers up to 1992 (1:2.5) is suggested to be a consequence of low baseline risks for lung cancer mortality in Israel and dropping smoking levels. Exposure to asbestos use and asbestos in place remain, but total risk should drop after 2010 if imports continue to drop. These projections may be altered by trade between Israel and its neighbors following peace agreements. Reductions in risk will have resulted from reduction in exposure brought about by reductions in manufacture and use.}, } @article {pmid8684294, year = {1995}, author = {Rösler, JA and Woitowitz, HJ}, title = {Recent data on cancer due to asbestos in Germany.}, journal = {La Medicina del lavoro}, volume = {86}, number = {5}, pages = {440-448}, pmid = {8684294}, issn = {0025-7818}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Cohort Studies ; Data Interpretation, Statistical ; Female ; Follow-Up Studies ; Germany/epidemiology ; Germany, West/epidemiology ; Humans ; Lung Neoplasms/epidemiology/*etiology ; Male ; Mesothelioma/epidemiology/*etiology ; Middle Aged ; *Occupational Exposure ; Occupations ; Peritoneal Neoplasms/epidemiology/*etiology ; Pleural Neoplasms/epidemiology/*etiology ; Registries ; Risk Factors ; Smoking/adverse effects ; Time Factors ; }, abstract = {The Authors evaluate the risk of lung cancer and mesothelioma among asbestos workers in Germany. 3,988 workers (3,372 male and 616 female) were included in the study, which took into consideration the branch of the asbestos industry in which they had worked, the duration of their employment and also their smoking habits. At the end of the 12 year follow-up, 3,315 workers were alive and 673 dead. The analysis of cause of death showed an increased risk of dying from lung cancer and pleural and peritoneal mesothelioma, in men as well as in women. The risk was shown to be greatest among workers in the asbestos textile industry and among insulators. A probable multiplicative effect of asbestos exposure and smoking on lung cancer causation was noted.}, } @article {pmid8684293, year = {1995}, author = {Englund, A}, title = {Recent data on cancer due to asbestos in Sweden.}, journal = {La Medicina del lavoro}, volume = {86}, number = {5}, pages = {435-439}, pmid = {8684293}, issn = {0025-7818}, mesh = {Asbestos/*adverse effects ; Cohort Studies ; Female ; Humans ; Lung Neoplasms/epidemiology/*etiology ; Male ; Mesothelioma/epidemiology/*etiology ; *Occupational Exposure ; Occupations ; Pleural Neoplasms/epidemiology/*etiology ; Registries ; Risk Factors ; Sex Factors ; Sweden/epidemiology ; }, abstract = {Asbestos exposure in Sweden rapidly grew in the '50s and '60s, and then began to drop at the beginning of the '70s. The number of pleural mesotheliomas due to this exposure increased to some 80 a year during the second half of the '80s, and is rapidly increasing. The jobs with the highest risk are the wood and pulp industry, plumbing, shipbuilding, and, most of all, railroad manufacturing and sugar refineries. Data dealing with peritoneal mesotheliomas are more uncertain, and possibly misleading. As far as lung cancer incidence is concerned, it remains high in plumbers and insulators, while it declined to the expected levels in the other categories of exposed workers.}, } @article {pmid8684292, year = {1995}, author = {Huuskonen, MS and Karjalainen, A and Tossavainen, A and Rantanen, J}, title = {Asbestos and cancer in Finland.}, journal = {La Medicina del lavoro}, volume = {86}, number = {5}, pages = {426-434}, pmid = {8684292}, issn = {0025-7818}, mesh = {Age Factors ; Aged ; Asbestos/*adverse effects ; Asbestos, Amosite/adverse effects ; Asbestos, Amphibole/adverse effects ; Asbestos, Crocidolite/adverse effects ; Asbestos, Serpentine/adverse effects ; Asbestosis/*epidemiology/prevention & control ; Female ; Finland/epidemiology ; Forecasting ; Humans ; Lung Neoplasms/epidemiology/*etiology ; Male ; Mesothelioma/epidemiology/*etiology ; Middle Aged ; Occupational Health ; Occupations ; Peritoneal Neoplasms/epidemiology/*etiology ; Pleural Neoplasms/epidemiology/*etiology ; }, abstract = {Primary prevention carried out today can reduce the disease incidence in the future decades. The present disease panorama is the consequence of past asbestos exposure mainly before the 1970s. The peak incidence of asbestos-induced diseases will be reached around 2010 in Finland. The number of asbestos-related premature deaths is at present annually about 150 which exceeds the figure of fatal work accidents. Asbestos-related cancer will increase still for 15-20 years and reach its maximum, about 300 cases, in 2010, and will start to decrease after that. More than 20,000 asbestos-exposed workers have participated in the medical screening and follow-up. The termination of exposure, antismoking campaigns, improved diagnostics and careful attention to compensation issues, as well as other potentials for prevention, were the central issue of the Asbestos Program of the Finnish Institute of Occupational Health. An important objective of research work is to improve early diagnostics, and thereby treatment prospects, in case of asbestos-induced cancers.}, } @article {pmid8684290, year = {1995}, author = {Nicholson, WJ and Raffn, E}, title = {Recent data on cancer due to asbestos in the U.S.A. and Denmark.}, journal = {La Medicina del lavoro}, volume = {86}, number = {5}, pages = {393-410}, pmid = {8684290}, issn = {0025-7818}, mesh = {Asbestos/*adverse effects ; Asbestos, Amosite/adverse effects ; Asbestos, Amphibole/adverse effects ; Asbestos, Crocidolite/adverse effects ; Asbestos, Serpentine/adverse effects ; Carcinoma, Bronchogenic/*epidemiology/etiology ; Cohort Studies ; Denmark/epidemiology ; Female ; Humans ; Lung Neoplasms/*epidemiology/etiology ; Male ; Mesothelioma/*epidemiology/etiology ; Models, Statistical ; Occupational Exposure ; Occupations ; Risk Factors ; Time Factors ; United States/epidemiology ; }, abstract = {The Authors present data, from the USA and Denmark, dealing with the carcinogenicity of chrysotile. This review considers epidemiological studies on the incidence of bronchogenic carcinoma and mesothelioma in populations exposed to commercial chrysotile and to mixtures of chrysotile and commercial amphiboles, with which the chrysotile is often contaminated. The analyses demonstrate that the risk of lung cancer is similar for chrysotile, amosite and crocidolite on a fiber exposure basis. Chrysotile and amosite appear to produce equal mesothelioma risks. The risk of mesothelioma is four to ten times greater for crocidolite.}, } @article {pmid8684289, year = {1995}, author = {Zampi, G and Comin, CE and Dini, S}, title = {Mesothelioma as a risk indicator of asbestos exposure: the role of the pathologist.}, journal = {La Medicina del lavoro}, volume = {86}, number = {5}, pages = {389-392}, pmid = {8684289}, issn = {0025-7818}, mesh = {Asbestosis/*diagnosis/pathology ; Biomarkers ; Diagnosis, Differential ; Histocytochemistry ; Humans ; Immunohistochemistry ; Mesothelioma/diagnosis/*pathology ; Microscopy, Electron ; *Occupational Exposure ; Pleura/pathology ; Pleural Neoplasms/diagnosis/*pathology ; Risk Factors ; }, abstract = {Malignant mesothelioma is an uncommon tumour, which has become an important epidemiological marker for exposure to asbestos. This tumour is characterised by a wide range of microscopic features which may be classified in three histologic patterns: epithelial, mesenchimal and mixed or biphasic. Histochemical staining is often necessary to distinguish mesothelioma from carcinoma. As regards immunohistochemistry, only the use of a combination of antibodies significantly decreases the risk of false-negative results. Analytic electron microscopy techniques may also be useful, permitting the evaluation of the cumulative fiber burden in the target organ.}, } @article {pmid8645115, year = {1995}, author = {Curin, K and Sarić, M}, title = {Cancer of the lung, pleura, larynx and pharynx in an area with an asbestos-cement plant.}, journal = {Arhiv za higijenu rada i toksikologiju}, volume = {46}, number = {3}, pages = {289-300}, pmid = {8645115}, issn = {0004-1254}, mesh = {Air Pollutants, Occupational/*adverse effects ; Alcohol Drinking ; Asbestos/*adverse effects ; *Carcinogens ; Croatia/epidemiology ; Female ; Humans ; Laryngeal Neoplasms/epidemiology/*etiology ; Lung Neoplasms/epidemiology/*etiology ; Male ; Pharyngeal Neoplasms/epidemiology/*etiology ; Pleural Neoplasms/epidemiology/*etiology ; Smoking/adverse effects ; }, abstract = {Data on persons who died of cancer of the respiratory tract and pharynx in a Croatian coastal area with an asbestos-cement industry were collected and analysed for the period 1970-1990. Cancer mortality data were obtained from the Cancer Registry of Croatia. By the poll method, additional data on occupation, life style (smoking, alcohol drinking), length of residence in the area, educational level and cancer mortality among the relatives were obtained. The results of the investigation showed that the mortality rates for the lung, larynx and pharynx cancers, standardized according to age, were lower in the study area than expected (data for Croatia). Standardized mortality rates for mesothelioma were higher in the area under study for both sexes (except for women in the rural part of the area) than in Croatia. Within the study area the highest mortality rates for follow-up cancers were registered in the settlement where the asbestos-cement plant was located. Some settlements in two municipalities within the area also had higher mortality rates caused by these tumours in comparison with the rest of the study area or Croatia as a whole. In the evaluation of the obtained findings possible uneven distribution of emissions from the asbestos-cement plant caused by prevailing wind and air stream direction were considered.}, } @article {pmid7590386, year = {1995}, author = {Shterengartz, RIa and Boiarchuk, IF and Dorfman, AA and Siriachenko, SS}, title = {[Sanitary-hygienic regulations of the utilization of asbestos production waste in railway facilities].}, journal = {Gigiena i sanitariia}, volume = {}, number = {5}, pages = {55-57}, pmid = {7590386}, issn = {0016-9900}, mesh = {Adult ; Age Factors ; Asbestos/*adverse effects ; Asbestosis/*etiology/prevention & control ; Dust ; Female ; Humans ; Lung Neoplasms/*etiology/prevention & control ; Male ; Maximum Allowable Concentration ; Mesothelioma/*etiology/prevention & control ; Middle Aged ; *Occupational Exposure ; *Railroads ; Sanitation/*standards ; Time Factors ; }, abstract = {The hazards of utilizing the asbestos production wastes in railway construction are analyzed. An increased risk of cancer development was observed only in groups exposed to asbestos in concentrations surpassing the maximal permissible level, as shown by mortality records. The authors come to a conclusion that the use of asbestos waste is permissible only on condition of strict adherence to sanitary regulations.}, } @article {pmid7485191, year = {1995}, author = {Dell, L and Teta, MJ}, title = {Mortality among workers at a plastics manufacturing and research and development facility: 1946-1988.}, journal = {American journal of industrial medicine}, volume = {28}, number = {3}, pages = {373-384}, doi = {10.1002/ajim.4700280307}, pmid = {7485191}, issn = {0271-3586}, mesh = {Adolescent ; Adult ; Cause of Death ; Cohort Studies ; Humans ; Leukemia/chemically induced/mortality ; Male ; Mesothelioma/chemically induced/mortality ; Middle Aged ; Neoplasms/chemically induced/*mortality ; Occupational Diseases/chemically induced/*mortality ; Pancreatic Neoplasms/chemically induced/mortality ; *Plastics ; Pleural Neoplasms/chemically induced/mortality ; Time Factors ; }, abstract = {Mortality through 1988 was studied for 5,932 male employees who worked between January 1, 1946 and December 31, 1967 at a New Jersey plastics manufacturing and research and development facility. The cohort was followed for an average of 32 years and included 1,859 deaths. Potential exposures included asbestos, formaldehyde, and polyvinyl chloride (PVC). Mortality rates for the cohort were compared to both U.S. and state mortality rates, and analyses were also performed by lagging duration of employment. Based on U.S. rates, mortality among hourly males (n = 3,853) from all cancers was similar to expected [standardized mortality ratio (SMR), 102; 95% confidence interval (CI), 92-114]. Excess mortality among hourly workers was seen for pancreatic cancer (SMR, 146; 95% CI, 95-216) and "malignancies of other parts of the respiratory system" (SMR, 373; 95% CI, 121-870). The latter excess was due entirely to five deaths from pleural mesothelioma. There were no deaths identified due to nasal cavity or nasopharyngeal cancers, or angiosarcoma of the liver. Mortality from leukemia among research and development workers (n = 1,421) was significantly elevated (SMR, 265; 95% CI, 115-524) and related to assignment to process development. This study verifies the excess of pancreatic cancer among workers at the facility seen in earlier studies and observes excesses of mesothelioma due to asbestos exposure and leukemia in process development workers.}, } @article {pmid7627973, year = {1995}, author = {Rutten, AA and Bermudez, E and Stewart, W and Everitt, JI and Walker, CL}, title = {Expression of insulin-like growth factor II in spontaneously immortalized rat mesothelial and spontaneous mesothelioma cells: a potential autocrine role of insulin-like growth factor II.}, journal = {Cancer research}, volume = {55}, number = {16}, pages = {3634-3639}, pmid = {7627973}, issn = {0008-5472}, mesh = {Animals ; Cell Division ; Cells, Cultured ; Epithelial Cells ; Epithelium/*metabolism ; Gene Expression ; Insulin-Like Growth Factor I/metabolism ; Insulin-Like Growth Factor II/*metabolism ; Male ; Mesothelioma/*metabolism/pathology ; RNA, Messenger/genetics ; RNA, Neoplasm/genetics ; Rats ; Rats, Inbred F344 ; Receptor, IGF Type 1/metabolism ; Receptor, IGF Type 2/metabolism ; Tumor Cells, Cultured ; }, abstract = {Insulin-like growth factors (IGFs) are polypeptides that play an important role in cellular proliferation and differentiation. The present study examines the role of IGFs in the growth of mesothelial cells. Cell lines derived from normal rat mesothelium as well as lines derived from spontaneous rat mesotheliomas were found to express RNA transcripts for IGF-II. In contrast, cell lines derived from asbestos-induced rat mesotheliomas did not express this growth factor. All cell lines expressed receptors for IGF-I and IGF-II, as well as insulin receptors. Coexpression of IGF-II and its cognate receptor suggested that IGF-II was acting as an autocrine growth factor in the spontaneously immortalized cells and the cells derived from the spontaneous tumors. The biological activity of IGF-II secreted by the cell lines into conditioned medium could be neutralized using an IGF-II-specific antibody. Growth was inhibited in a dose-dependent manner; at the highest antibody concentration used (100 micrograms anti-IGF-II/ml), cell growth was decreased to 47% of control values. This inhibition was partially reversible by treatment of the cultures with IGF-II (91% of the control). These data suggest that IGF-II expression may be involved in the spontaneous alteration of rat mesothelial cells and may function as an autocrine or paracrine growth factor to modulate the growth of these cells in vitro and in vivo. Ubiquitous expression of IGF-II by cells that have not been exposed to asbestos and the lack of IGF-II expression by asbestos-transformed cells suggest that the mechanisms of changes in growth factor expression differ in mesothelial cells transformed by different pathways.}, } @article {pmid8625125, year = {1995}, author = {Shannon, VR and Nesbitt, JC and Libshitz, HI}, title = {Malignant pleural mesothelioma after radiation therapy for breast cancer. A report of two additional patients.}, journal = {Cancer}, volume = {76}, number = {3}, pages = {437-441}, doi = {10.1002/1097-0142(19950801)76:3<437::aid-cncr2820760314>3.0.co;2-a}, pmid = {8625125}, issn = {0008-543X}, mesh = {Aged ; Breast Neoplasms/*radiotherapy ; Female ; Humans ; Mesothelioma/diagnostic imaging/*etiology/pathology ; *Neoplasms, Radiation-Induced/diagnostic imaging/pathology ; Pleural Neoplasms/diagnostic imaging/*etiology/pathology ; Radiography ; Radiotherapy/*adverse effects ; Retrospective Studies ; }, abstract = {BACKGROUND: Malignant pleural mesotheliomas (MPMs) are rare tumors that usually have a fatal outcome. The association of these tumors with asbestos exposure is well established. Induction of malignant mesothelioma by nonasbestos-related causes also has been reported in the literature, although the number of documented cases is extremely small. Two additional patients with malignant pleural mesothelioma many years after radiotherapy for breast cancer are reported.

METHODS: The observations as reported in the literature on the involvement of radiation in the development of MPMs are reviewed and compared with the authors' clinical experience. In a retrospective random review, 1000 patients who received thoracic irradiation at M. D. Anderson Cancer Center were studied for histologic and radiographic evidence of MPM. The selection criteria included the development of a unilateral pleural effusion years after successful treatment with thoracic irradiation for a proven malignancy. Patients with a history compatible with asbestos exposure were excluded from the review.

RESULTS: There have been only three previous cases of documented MPM associated with thoracic irradiation reported in the English literature. A review of the experience at our institution has demonstrated three patients with radiation-induced MPM. One patient has been reported elsewhere. Details of the other two patients are discussed in this paper.

CONCLUSIONS: Nonasbestos-related causes of MPMs are rare. The additional two patients lend added support to the association between thoracic irradiation and the development of MPM. The development of a unilateral pleural effusion occurring years after successful treatment of a proven malignancy with thoracic irradiation should alert the clinician to the possibility of MPM.}, } @article {pmid8625124, year = {1995}, author = {Zhou, J and Iwasa, Y and Konishi, I and Kan, N and Kannagi, R and Kobashi, Y and Kim, YC and Yamabe, H}, title = {Papillary serous carcinoma of the peritoneum in women. A clinicopathologic and immunohistochemical study.}, journal = {Cancer}, volume = {76}, number = {3}, pages = {429-436}, doi = {10.1002/1097-0142(19950801)76:3<429::aid-cncr2820760313>3.0.co;2-8}, pmid = {8625124}, issn = {0008-543X}, mesh = {Adult ; Aged ; Cystadenocarcinoma, Papillary/chemistry/diagnosis/*pathology ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; Mesothelioma/chemistry/diagnosis/pathology ; Middle Aged ; Ovarian Neoplasms/chemistry/pathology ; Peritoneal Neoplasms/chemistry/*pathology ; }, abstract = {BACKGROUND: Papillary serous carcinoma of the peritoneum (PSCP) is a primary peritoneal tumor in women that histologically resembles papillary serous carcinoma of the ovary (PSCO). Recognition of PSCP as an entity is controversial, as is the histogenesis, histopathologic differential diagnosis, and treatment.

METHODS: Ten cases of PSCP retrieved from the pathology files of 4 hospitals in Kyoto and Nara, Japan, were studied clinicopathologically and immunohistochemically.

RESULTS: Patient ages at presentation ranged from 40 to 74 years (median, 56 years). All patients were Asian (Japanese). None of the patients had a history of asbestos exposure. Most of the patients had abdominal swelling, ascites with positive cytology, and elevated serum CA125. At surgery, omental tumors with dissemination to the abdominal and pelvic peritoneum were found in all patients. The histology was similar to that of Grade 2 to 3 PSCO. Immunohistochemical studies using a panel of monoclonal antibodies against carbohydrates showed that Lewis Y is a good marker, in addition to S-100, placental alkaline phosphatase, CA125, and CD15 for separating PSCP from malignant mesothelioma (MM). With cytoreductive surgery and cisplatin-based combination chemotherapy and in some cases adoptive immunotherapy and radiation, a median survival of 27 months and a 5-year survival rate of 27% were attained. One patient with Grade 3 tumor has survived for more than 6 years after surgery.

CONCLUSIONS: (1) Papillary serous carcinoma of the peritoneum is a definite clinicopathologic entity; (2) immunohistochemistry is a useful tool for distinguishing PSCP from MM; (3) cytoreductive surgery and cisplatin-based combination chemotherapy with other adjunct therapies such as immunotherapy and radiation may improve patient survival in PSCP.}, } @article {pmid8553007, year = {1995}, author = {Wong, O}, title = {Pleural mesothelioma in oil refinery workers.}, journal = {Scandinavian journal of work, environment & health}, volume = {21}, number = {4}, pages = {301-309}, doi = {10.5271/sjweh.1365}, pmid = {8553007}, issn = {0355-3140}, mesh = {Adult ; Age Distribution ; Aged ; Asbestos/adverse effects ; *Chemical Industry ; Cohort Studies ; Humans ; Incidence ; Italy/epidemiology ; Lung Neoplasms/epidemiology/etiology ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Occupational Diseases/*epidemiology ; Occupational Exposure/adverse effects ; Pleural Neoplasms/*epidemiology ; Reproducibility of Results ; Risk Factors ; Survival Rate ; }, } @article {pmid8552999, year = {1995}, author = {Rogers, A and Nevill, M}, title = {Occupational and environmental mesotheliomas due to crocidolite mining activities in Wittenoom, Western Australia.}, journal = {Scandinavian journal of work, environment & health}, volume = {21}, number = {4}, pages = {259-264}, doi = {10.5271/sjweh.35}, pmid = {8552999}, issn = {0355-3140}, mesh = {Adolescent ; Adult ; Asbestos, Crocidolite/*adverse effects ; Asbestosis/*epidemiology/etiology ; Child ; Environmental Exposure/adverse effects ; Female ; Humans ; Incidence ; Lung Neoplasms/*epidemiology/etiology ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Mining ; Occupational Diseases/*epidemiology/etiology ; Occupational Exposure/*adverse effects ; Registries ; Risk Assessment ; Western Australia/epidemiology ; }, abstract = {OBJECTIVES: The aim of the study was to review existing cases, calculate rates, and predict future numbers of occupational and environmental mesotheliomas from Wittenoom.

METHODS: On the basis of information contained in occupational and environmental histories, Wittenoom cases were extracted from national records collected since 1979. Occupational and residential population estimates were obtained from company and government records. The proportional latency method was used to predict the numbers of mesotheliomas prior to and after the data collection phase. Airborne fiber monitoring was used to calculate risk due to current levels of contamination in the mine and town environments.

RESULTS: During 1979-1994, Wittenoom cases (N = 176) comprised approximately 6% of the mesothelioma cases recorded in Australia. Of these 122 were employed directly in the mining and milling activities, another 18 were involved in the transport of raw fiber or tailings, and 34 were town residents or visitors. Due to past exposures, additional occupational (N = 301) and environmental (N = 83) cases can be expected. Dependent on residential time, existing levels of contamination may result in a risk of between < 1 to 57 per million of the population.

CONCLUSIONS: Latency effects will result in considerable numbers of mesotheliomas appearing over the next 10-20 years in Wittenoom. The cessation of mining activities and major clean up of the town will result in reduced mesothelioma cases.}, } @article {pmid8532693, year = {1995}, author = {Srebro, SH and Roggli, VL and Samsa, GP}, title = {Malignant mesothelioma associated with low pulmonary tissue asbestos burdens: a light and scanning electron microscopic analysis of 18 cases.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {8}, number = {6}, pages = {614-621}, pmid = {8532693}, issn = {0893-3952}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects/analysis ; Female ; Humans ; Lung/*chemistry ; Lung Neoplasms/chemistry/*etiology/pathology ; Male ; Mesothelioma/chemistry/*etiology/pathology ; Microscopy, Electron, Scanning ; Middle Aged ; Mineral Fibers/analysis ; Retrospective Studies ; }, abstract = {Most malignant mesothelioma cases are associated with pulmonary asbestos body (AB) counts significantly greater than those of the general population. However, the question remains whether malignant mesothelioma cases associated with "normal" AB counts (i.e., indistinguishable from the general population) represent background incidence levels or are, actually, asbestos related. We performed AB counts (by light microscopy) and mineral fiber analysis (by scanning electron microscopy) in 18 mesothelioma cases with AB counts within our normal range (0 to 20 AB/G wet lung) and in 19 "control" cases. Our study demonstrated that approximately one-third (6 of 18) of the mesothelioma cases have asbestos fiber burdens greater than 95% of the control levels. These results suggest that these six mesothelioma cases may be asbestos related despite AB counts similar to those of the general population. An asbestos etiology was suggested in three additional cases, but too few amphibole fibers were identified in these cases to be certain of a value above background. The remaining nine cases showed no evidence of an asbestos etiology. Electron microscopic analysis of pulmonary mineral fibers may be required to differentiate asbestos-related mesotheliomas from non-asbestos-related cases when AB counts are within the range of background values.}, } @article {pmid8528480, year = {1995}, author = {Donington, JS and Mew, DJ and Pass, HI}, title = {Malignant pleural mesothelioma: newer aspects of carcinogenesis, molecular genetics, and prospects for future therapies.}, journal = {Surgical oncology}, volume = {4}, number = {4}, pages = {175-185}, doi = {10.1016/s0960-7404(10)80034-9}, pmid = {8528480}, issn = {0960-7404}, mesh = {Asbestosis/complications ; Base Sequence ; Chromosome Aberrations/etiology ; Chromosome Disorders ; Cytokines/metabolism ; DNA Damage ; Genes, Tumor Suppressor ; Genetic Therapy ; Humans ; *Mesothelioma/etiology/genetics/metabolism/therapy/virology ; Molecular Sequence Data ; *Pleural Neoplasms/etiology/genetics/metabolism/therapy/virology ; Reactive Oxygen Species/metabolism ; Simian virus 40/genetics ; }, abstract = {Malignant pleural mesothelioma (MPM) is an asbestos-related disease which, although rare, is having a major social impact, and is, for the majority of cases, an incurable illness. There has been a surge of information regarding data on mesothelial transformation, mesothelioma molecular genetics and somatic gene therapy for this disease. This report summarizes the most recent investigations attempting to characterize the behaviour, on a cellular and molecular level, of MPM, with an emphasis on data from investigations performed at the National Cancer Institute with our collaborators.}, } @article {pmid7662930, year = {1995}, author = {Ross, DJ and Sallie, BA and McDonald, JC}, title = {SWORD '94: surveillance of work-related and occupational respiratory disease in the UK.}, journal = {Occupational medicine (Oxford, England)}, volume = {45}, number = {4}, pages = {175-178}, doi = {10.1093/occmed/45.4.175}, pmid = {7662930}, issn = {0962-7480}, mesh = {Adult ; Aged ; Asthma/epidemiology ; Female ; Follow-Up Studies ; Humans ; Lung Diseases/*epidemiology ; Male ; Mesothelioma/epidemiology ; Middle Aged ; Occupational Diseases/*epidemiology ; Population Surveillance ; United Kingdom/epidemiology ; }, abstract = {Chest and occupational physicians participating in SWORD are estimated to have seen some 3300 cases of work-related respiratory disease in 1994, similar to the totals for 1992-1993. Occupational asthma was the single most frequent diagnosis (941 cases), but asbestos exposure was considered the cause in 1529 cases of diseases of long latency. Large-scale follow-up studies showed (i) that most patients with occupational asthma failed to recover and that half had left their employer, and (ii) that many patients had long-term respiratory illness including asthma following inhalation accidents. Over the six years of the scheme there have been slight changes in attributed agents for occupational asthma and in the frequency of various diagnoses; for example, there has been a gradual reduction in reports of pneumoconiosis. A decline with birth cohort in the proportion of mesotheliomas in men employed in shipyards is shown, with some evidence of a compensatory trend in construction trades.}, } @article {pmid7570451, year = {1995}, author = {Hughes, P and McGavin, CR}, title = {Pleural mesothelioma with non-Hodgkin's lymphoma.}, journal = {Thorax}, volume = {50}, number = {8}, pages = {915}, pmid = {7570451}, issn = {0040-6376}, mesh = {Asbestos/*adverse effects ; Humans ; *Leukemia, Lymphocytic, Chronic, B-Cell/*etiology ; Male ; *Mesothelioma ; Middle Aged ; Neoplasms, Multiple Primary/*etiology ; *Pleural Neoplasms ; *Stomach Neoplasms/*etiology ; }, } @article {pmid7542832, year = {1995}, author = {Stey, C and Landolt-Weber, U and Vetter, W and Sauter, C and Marincek, B}, title = {Malignant peritoneal mesothelioma after Thorotrast exposure.}, journal = {American journal of clinical oncology}, volume = {18}, number = {4}, pages = {313-317}, doi = {10.1097/00000421-199508000-00009}, pmid = {7542832}, issn = {0277-3732}, mesh = {Adenocarcinoma/diagnosis ; Ascites/etiology/pathology ; Bleomycin/administration & dosage/adverse effects/*therapeutic use ; Combined Modality Therapy ; Diagnosis, Differential ; Drainage ; Humans ; Injections, Intraperitoneal ; Male ; Mesothelioma/*chemically induced/diagnosis/secondary/*therapy ; Middle Aged ; Peritoneal Neoplasms/*chemically induced/diagnosis/*therapy ; Pleural Effusion, Malignant/etiology/pathology ; Pleurodesis ; Thorium Dioxide/*adverse effects ; Tomography, X-Ray Computed ; }, abstract = {A case of a malignant peritoneal mesothelioma in a 63-year-old male patient with a history of exposure to Thorotrast in 1945 is presented. There was no history of exposure to asbestos. The clinical manifestation was a serosal effusion, which required weekly ascites puncture until therapy with intraperitoneal bleomycin was initiated. The latter treatment led to a significant reduction of ascites without any influence on tumor progression. Unfortunately, intraperitoneal bleomycin was accompanied by pulmonary toxicity, but at a higher total dose than known for intravenous administration. Three years after diagnosis the patient is still alive, without relapse of ascites production after bleomycin had to be stopped. Considering the risk of pulmonary fibrosis with high-dose intraperitoneal bleomycin and the lack of efficacy on tumor reduction, bleomycin seems to offer no advantage with respect to cisplatin.}, } @article {pmid7616885, year = {1995}, author = {Leigh, J}, title = {Mesothelioma: is asbestos exposure the only cause?.}, journal = {The Medical journal of Australia}, volume = {163}, number = {2}, pages = {105-106}, pmid = {7616885}, issn = {0025-729X}, mesh = {Asbestos/*adverse effects ; Environmental Exposure ; Female ; Humans ; Lung Neoplasms/*etiology ; Male ; Mesothelioma/*etiology ; }, } @article {pmid7606714, year = {1995}, author = {Hirvonen, A and Pelin, K and Tammilehto, L and Karjalainen, A and Mattson, K and Linnainmaa, K}, title = {Inherited GSTM1 and NAT2 defects as concurrent risk modifiers in asbestos-related human malignant mesothelioma.}, journal = {Cancer research}, volume = {55}, number = {14}, pages = {2981-2983}, pmid = {7606714}, issn = {0008-5472}, mesh = {Adult ; Aged ; Arylamine N-Acetyltransferase/*genetics ; Asbestos/*adverse effects ; *Cocarcinogenesis ; Evaluation Studies as Topic ; Female ; Genes, Regulator ; Genotype ; Glutathione Transferase/*genetics ; Humans ; Isoenzymes/*genetics ; Male ; Mesothelioma/enzymology/*etiology/*genetics ; Middle Aged ; Polymorphism, Genetic/genetics ; Risk Factors ; }, abstract = {Besides asbestos exposure, the factors that determine susceptibility to malignant mesothelioma are unknown. We evaluated the risk of GSTM1 null genotype and slow acetylation-associated NAT2 genotype for malignant mesothelioma in relation to asbestos exposure. Both the GSTM1 null genotype and the NAT2 slow acetylator genotype placed individuals at about 2-fold increased risk of developing malignant mesothelioma [odds ratio (OR) = 1.8, 95% confidence interval (CI) = 1.0-3.5 and OR = 2.1, 95% CI = 1.1-4.1, for the GSTM1 and NAT2 genes, respectively]. When the patients were divided into low/moderate and high exposure groups according to their asbestos exposure histories, the effect of the at-risk genotypes was mostly attributable to the high exposure groups (OR = 2.3, 95% CI = 1.0-5.6 and OR = 3.7, 95% CI = 1.3-10.2, for the GSTM1 and NAT2 genes, respectively). The individuals with combined GSTM1 and NAT2 defects had about a 4-fold risk of developing malignant mesothelioma compared to those with the GSTM1 gene and NAT2 fast acetylator genotype (OR = 3.6; 95% CI = 1.3-9.6). Moreover, the risk among subjects highly exposed to asbestos with the double at-risk genotype was more than 7-fold greater compared to those with the more beneficial genotypes of both GSTM1 and NAT2 genes (OR = 7.4; 95% CI = 1.6-34.0).}, } @article {pmid9363074, year = {1995}, author = {Hillerdal, G}, title = {Pleural malignancies including mesothelioma.}, journal = {Current opinion in pulmonary medicine}, volume = {1}, number = {4}, pages = {339-343}, pmid = {9363074}, issn = {1070-5287}, mesh = {*Asbestosis ; Humans ; *Mesothelioma ; Pleural Effusion, Malignant ; *Pleural Neoplasms ; Pleurodesis ; }, abstract = {Malignant mesothelioma is caused almost exclusively by occupational exposure to asbestos. During the past few years, however, increasing evidence has mounted that background exposure to asbestos could be sufficient to cause mesothelioma. Treatment of malignant mesothelioma remains a big problem. Some new approaches are on their way, and the most exciting ones are local immunotherapy in very early cases. Some success has been reported with local interferon treatment. As for treatment of metastatic pleural disease, the main purpose is symptomatic relief of dyspnea caused by fluid accumulation. The best way to achieve a lasting palliation is pleurodesis, and the most common way to do this, is by chemical means. The drug of choice in the United States has for many years been tetracycline, but since injectable tetracycline is no longer available, some substitute must be found. The substance that will "win" is not yet clear, but the two leading contestants are talc and doxycycline. Bleomycin also has its supporters, and a dark horse is quinacrine, which although not easily available in the United States, has been used in many European centers for decades.}, } @article {pmid7793480, year = {1995}, author = {Jones, MA and Young, RH and Scully, RE}, title = {Malignant mesothelioma of the tunica vaginalis. A clinicopathologic analysis of 11 cases with review of the literature.}, journal = {The American journal of surgical pathology}, volume = {19}, number = {7}, pages = {815-825}, doi = {10.1097/00000478-199507000-00010}, pmid = {7793480}, issn = {0147-5185}, mesh = {Adult ; Aged ; Child ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Mesothelioma/metabolism/*pathology/therapy ; Middle Aged ; Vaginal Neoplasms/metabolism/*pathology/therapy ; }, abstract = {Eleven malignant mesotheliomas of the testicular tunica vaginalis occurred in patients aged 12 to 76 (mean, 54.1) years. Hydrocele, with or without an associated mass, or appreciation of a paratesticular mass accounted for the clinical presentation. One patient had a history of asbestos exposure. Grossly, the tumors typically presented as multiple nodules studding a hydrocele sac, frequently associated with a mass infiltrating the spermatic cord or adjacent testis. Microscopically, five tumors were epithelial and six biphasic, with the typical architectural and cytologic features of mesothelioma. Mixtures of papillary, tubular, and solid patterns predominated in the epithelial areas; interlacing fascicles of spindle cells with scanty stroma characterized the sarcomatous components. All eight of the tumors that were stained for keratin (AE1/AE3) were positive, four of five for epithelial membrane antigen, and four of five for vimentin. Seven of seven tumors were carcinoembryonic antigen negative and five of five B72.3, Leu-M1, and Ber-Ep4 negative. Follow-up ranging from 1 to 15 (mean, 4.3) years was available for seven patients. Three died of disease after 4, 4, and 3 years, and three are alive with disease 2, 2, and 15 years after diagnosis. Two of the latter three patients had extensive local recurrences, one 15 years after the diagnosis of a well-differentiated papillary mesothelioma, the other 2 years following treatment with hydrocelectomy only. One patient who has been followed for only 1 year has no evidence of disease. This series emphasizes a number of important features of testicular mesothelioma; (a) a wide age range with occasional occurrence at a young age, (b) a wide morphologic spectrum with regard to degree of differentiation, and (c) an aggressive natural history with a potential for late recurrence or metastasis of even well-differentiated tumors, suggesting the need for initial aggressive surgical treatment.}, } @article {pmid7670617, year = {1995}, author = {Glass, LR and Brown, RC and Hoskins, JA}, title = {Health effects of refractory ceramic fibres: scientific issues and policy considerations.}, journal = {Occupational and environmental medicine}, volume = {52}, number = {7}, pages = {433-440}, pmid = {7670617}, issn = {1351-0711}, mesh = {Adenocarcinoma/etiology ; Adenoma/etiology ; Aluminum Silicates/*adverse effects/chemistry ; Animals ; Carcinogenicity Tests ; Case-Control Studies ; *Ceramics ; Cohort Studies ; Cricetinae ; Humans ; Longitudinal Studies ; Mesothelioma/etiology ; Occupational Exposure/adverse effects ; Pulmonary Fibrosis/etiology ; Rats ; Respiratory Function Tests ; }, abstract = {OBJECTIVES: To review the scientific literature on the health effects of refractory ceramic fibres (RCFs). The adverse effects of exposure to asbestos has led to concern about the potential for other fibrous materials to cause diseases. For this reason the human populations most heavily exposed to synthetic mineral fibres have been examined for any adverse effects and many types of fibre have been studied in animal experiments. One type of man made vitreous fibres (MMVFs), refractory ceramic fibres (RCFs), are principally used in thermal insulation at high temperatures--up to 1400 degrees C. As manufactured RCFs exist in a glassy, non-crystalline (sometimes called amorphous) state, they have various compositions, physical properties, and sized fibres.

METHODS: All reports on the health effects of RCFs available up to the end of 1994 have been examined and the scientific literature reviewed although all publications have not necessarily been referenced.

CONCLUSIONS: In recent inhalation experiments conducted with both rats and hamsters at the Research and Consulting Company, Geneva, at the highest dose tested (30 mg/m3) there was an increased incidence of tumours in both species. Lower doses were only examined in the rat and at these doses there was no significant excess of lung tumours. Epidemiological investigations of workers engaged in the manufacture of ceramic fibres have shown a small excess of pleural plaques. This phenomenon is being further investigated but could be due to confounding exposures. The populations available for study are small and their exposures fairly short, but it is considered prudent that they should remain under surveillance for some time to come. This is despite the fact that present exposures in the ceramic fibre industry are low (< 1 f/ml) and are being reduced.}, } @article {pmid7573074, year = {1995}, author = {Finkelstein, MM}, title = {Potential pitfall in using cumulative exposure in exposure-response relationships: demonstration and discussion.}, journal = {American journal of industrial medicine}, volume = {28}, number = {1}, pages = {41-47}, doi = {10.1002/ajim.4700280104}, pmid = {7573074}, issn = {0271-3586}, mesh = {Asbestos/adverse effects ; Case-Control Studies ; *Dose-Response Relationship, Drug ; Humans ; Logistic Models ; Lung Neoplasms/chemically induced/epidemiology ; Male ; Mesothelioma/chemically induced/epidemiology ; Occupational Exposure/*statistics & numerical data ; Peritoneal Neoplasms/chemically induced/epidemiology ; Random Allocation ; Reproducibility of Results ; *Research Design ; Risk Assessment ; Time Factors ; }, abstract = {Cumulative exposure is frequently used as a measure of exposure in the quantitative analysis of epidemiologic studies. It is recognized that the imposed symmetry between duration and intensity of exposure is a potential problem with this measure, but it is less widely recognized that the finding of an exposure-response relationship, using cumulative exposure as the exposure metric, does not necessarily imply that exposures were accurately or even consistently estimated. This report describes a simulation study drawn from a nested case-control analysis of mesothelioma in a cohort of asbestos cement workers. Intensity of exposure in the range of 0.1-40 fibers/ml was randomly assigned to subjects. Logistic regression analysis demonstrated that there was no association between mesothelioma risk and the randomly assigned intensity of exposure. However, in 171 (86%) of 200 trials, mesothelioma risk was significantly associated with cumulative exposure, even though intensity of exposure remained randomly assigned. A strong exposure-response relationship might thus be misleading. One would be more confident about quantitative risk assessment when there are a large number of independent studies available for analysis.}, } @article {pmid7573071, year = {1995}, author = {Huuskonen, MS and Koskinen, K and Tossavainen, A and Karjalainen, A and Rinne, JP and Rantanen, J}, title = {Finnish Institute of Occupational Health Asbestos Program 1987-1992.}, journal = {American journal of industrial medicine}, volume = {28}, number = {1}, pages = {123-142}, doi = {10.1002/ajim.4700280111}, pmid = {7573071}, issn = {0271-3586}, mesh = {Asbestosis/epidemiology/*prevention & control ; Environmental Monitoring ; Epidemiological Monitoring ; Finland/epidemiology ; Health Plan Implementation ; Health Policy ; Humans ; Lung Neoplasms/etiology/prevention & control ; Mass Screening ; Mesothelioma/etiology/prevention & control ; National Health Programs/*organization & administration ; *Occupational Health/legislation & jurisprudence ; Population Surveillance ; Research ; }, abstract = {In 1987-1992, the Finnish Institute of Occupational Health (FIOH) implemented a nationwide asbestos program aimed at preventing asbestos-related risks in good cooperation with governmental authorities, industry, trade unions, the health care and insurance systems, and mass media. The goals were to minimize all exposure to asbestos, identify people exposed at work, and improve the diagnostics of asbestos diseases, especially cancers. The program entailed several concrete actions and extensive dissemination of information, training, services, and scientific research. As proposed by the State Asbestos Committee, new use of asbestos products was banned and strict regulations were applied to renovation and inspection of old buildings. The screening study of asbestos-induced diseases included 18,943 current and retired workers from house building, shipyard, and asbestos industries. Pleural and parenchymal changes were found in 4,133 persons (22%), who were referred to further clinical examinations as suspected cases of an occupational disease. It was estimated that past exposure of asbestos among the Finnish population of 5 million causes > 150 mesotheliomas and lung cancers annually, totalling > 2,000 asbestos-induced cancer deaths by the year 2010. Although several major control actions were made or started during the program, the bulk of the preventive work still lies ahead.}, } @article {pmid7500899, year = {1995}, author = {Carnevale, F and Chellini, E}, title = {[The diffusion of information on the carcinogenicity of asbestos in the Italian scientific community before 1965].}, journal = {La Medicina del lavoro}, volume = {86}, number = {4}, pages = {295-302}, pmid = {7500899}, issn = {0025-7818}, mesh = {Asbestos/adverse effects/*history ; Asbestosis/complications/history ; Carcinogens/adverse effects/*history ; History, 20th Century ; Humans ; Information Services/*history ; Italy ; Lung Neoplasms/etiology/history ; Publishing/history ; }, abstract = {The spreading of information on asbestos carcinogenicity within the Italian scientific community before 1965. The paper deals with the development of recognition of asbestos carcinogenicity within the Italian scientific community. This development was difficult in Italy as in other countries. Articles and other papers in handbooks and congress proceedings, by Italian authors, published in the period 1934-1965, were considered. The first cases of lung cancer in Italian workers exposed to asbestos were observed in 1955-56, the first cases of malignant mesothelioma in 1965. The cases observed were very few, but knowledge on asbestos carcinogenicity became widespread within the Italian scientific community during the fifties (from 1953 on wards) with the publication of several handbooks of occupational medicine.}, } @article {pmid7793754, year = {1995}, author = {Roggli, VL}, title = {Malignant mesothelioma and duration of asbestos exposure: correlation with tissue mineral fibre content.}, journal = {The Annals of occupational hygiene}, volume = {39}, number = {3}, pages = {363-374}, doi = {10.1016/0003-4878(95)00006-z}, pmid = {7793754}, issn = {0003-4878}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects/analysis ; Female ; Humans ; Lung/ultrastructure ; Male ; Mesothelioma/*etiology ; Middle Aged ; Occupational Exposure/*adverse effects/analysis ; Time Factors ; }, abstract = {Among 441 cases of malignant mesothelioma in the author's files, there were 324 for whom reliable information was available regarding the duration of exposure to asbestos. Included were 298 pleural and 26 peritoneal mesotheliomas. The mean duration of exposure to asbestos was 23 +/- 14 years for all cases, and was not different for the pleural and peritoneal groups. Lung tissue was available for analysis of mineral fibre content in 94 cases. Linear regression analysis showed a significant correlation between duration of exposure and asbestos bodies per gramme of wet lung as determined by light microscopy, and between duration of exposure and total uncoated fibres (5 microns or greater in length) as well as commercial amphibole fibres per gramme as determined by scanning electron microscopy (P < 0.05). Individuals with direct exposures had on average higher asbestos contents than patients with indirect exposures. Furthermore, for each duration of exposure, shipyard workers had on average higher asbestos contents than non-shipyard workers (P < 0.05). Mesotheliomas are associated with a wide range of durations of exposure to asbestos and pulmonary asbestos burdens, and there is a rough correlation between duration of exposure and pulmonary commercial amphibole content.}, } @article {pmid7781415, year = {1995}, author = {Aisner, J}, title = {Current approach to malignant mesothelioma of the pleura.}, journal = {Chest}, volume = {107}, number = {6 Suppl}, pages = {332S-344S}, doi = {10.1378/chest.107.6_supplement.332s}, pmid = {7781415}, issn = {0012-3692}, mesh = {Antineoplastic Agents/therapeutic use ; Asbestos/adverse effects ; Combined Modality Therapy ; Humans ; Mesothelioma/etiology/pathology/surgery/*therapy ; Neoplasm Staging ; Pleura/surgery ; Pleural Neoplasms/etiology/pathology/surgery/*therapy ; Pneumonectomy ; }, abstract = {Malignant mesothelioma of the pleura occurs primarily in individuals who were exposed to asbestos either in the workplace or home. The incidence of malignant mesothelioma is rising and, reflective of the malignancy's long latency period, is expected to continue to increase into the next century. Current treatment measures, including surgery, radiation therapy, chemotherapy, intrapleural therapy, and combined-modality therapies, have had varying impacts on survival. This paper explores current trends in the treatment of malignant pleural mesothelioma.}, } @article {pmid7662082, year = {1995}, author = {Kraus, T and Heinritz, H and Raithel, HJ and Waldfahrer, F and Iro, H and Lehnert, G}, title = {[Asbestos dust-induced laryngeal carcinoma--a new occupational disease? Current scientific knowledge and social health regulations].}, journal = {Laryngo- rhino- otologie}, volume = {74}, number = {6}, pages = {371-374}, doi = {10.1055/s-2007-997760}, pmid = {7662082}, issn = {0935-8943}, mesh = {Aged ; Asbestosis/*etiology/prevention & control ; Dust/adverse effects ; Eligibility Determination/legislation & jurisprudence ; Expert Testimony/*legislation & jurisprudence ; Female ; Germany ; Humans ; Laryngeal Neoplasms/*etiology/prevention & control ; Male ; Middle Aged ; Occupational Exposure/*adverse effects ; Risk Factors ; Workers' Compensation/*legislation & jurisprudence ; }, abstract = {According to the current regulations pertaining to occupational diseases lung cancer and mesothelioma can be compensated as asbestos-related malignomas under certain circumstances. For several years there has been controversial discussion as to whether laryngeal carcinomas can also be caused by occupational asbestos exposure and should therefore be added to the list of occupational diseases. Critical evaluation of the available scientific knowledge with the scope of currently applicable regulations does not warrant adding asbestos-related laryngeal carcinomas to the list of occupational diseases at present. Further investigations are urgently necessary and may possibly bring new insights.}, } @article {pmid7627311, year = {1995}, author = {Magnani, C and Terracini, B and Ivaldi, C and Botta, M and Mancini, A and Andrion, A}, title = {Pleural malignant mesothelioma and non-occupational exposure to asbestos in Casale Monferrato, Italy.}, journal = {Occupational and environmental medicine}, volume = {52}, number = {6}, pages = {362-367}, pmid = {7627311}, issn = {1351-0711}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Female ; Humans ; Incidence ; Italy/epidemiology ; Male ; Mesothelioma/epidemiology/*etiology ; Middle Aged ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/epidemiology/*etiology ; Retrospective Studies ; Sex Factors ; }, abstract = {OBJECTIVES: To assess and quantify the occurrence of pleural malignant mesotheliomas in people who neither experienced occupational exposure to asbestos nor were married to (or known to live with) workers exposed to asbestos in the workplace. The study was conducted in the area of the local health authority of Casale Monferrato, in north western Italy, where a large factory that produced asbestos cement was active up to 1985. No other major activities related to asbestos have ever been present in the area.

METHODS: A retrospective survey covering the period 1980 to 1991 identified 126 incident pleural malignant mesotheliomas histologically diagnosed among residents in the local health authority (population at the 1981 census 98,000). Submission of 83 of 95 cases diagnosed during 1980-9 for revision by a panel of five expert pathologists led to the exclusion of 21. The 31 cases diagnosed in 1990-1 were not submitted for revision. For 64 of the 105 retained cases, information derived from different sources (rosters of the employees in the asbestos cement factory dated back to 1907, list of their spouses, clinical records) did not suggest occupational or paraoccupational exposure to asbestos.

RESULTS: Incidence excludes cases for which there was some suggestion of occupational or paraoccupational exposure to asbestos. Incidence of histologically confirmed malignant mesothelioma among residents in the local health authority (annual x 100,000; age adjusted) was 4.2 in men and 2.3 in women (based on 26 and 18 cases respectively). In both sexes, rates in 1985-9 were higher than in the previous quinquennium. Corresponding estimates for 1990-1 (based on unrevised diagnoses) suggest similar rates in men and women.

CONCLUSION: Rate ratios which are four to six times those measured by conventional Italian cancer registries can hardly be totally explained by bias produced by lack of recognition of occupational or paraoccupational exposure. The problem of proving this type of negative data is common to other circumstances of alleged cancer clusters of environmental (non occupational) origin.}, } @article {pmid7605169, year = {1995}, author = {Lee, RJ and Florida, RG and Stewart, IM}, title = {Asbestos contamination in paraffin tissue blocks.}, journal = {Archives of pathology & laboratory medicine}, volume = {119}, number = {6}, pages = {528-532}, pmid = {7605169}, issn = {0003-9985}, mesh = {Asbestos/*analysis ; Humans ; Mesothelioma/pathology ; Microscopy, Electron ; Omentum/pathology ; Paraffin/analysis ; *Paraffin Embedding ; Peritoneum/pathology ; Reproducibility of Results ; }, abstract = {Electron microscopic analyses of tissue samples embedded in paraffin are routinely performed as a means of validating (establishing) the asbestos exposure of persons diagnosed with mesothelioma, a rare form of cancer often identified as being caused by exposure to asbestos. During analysis of tissue samples claimed to contain asbestos, we observed asbestos contamination in the paraffin of the tissue block. To investigate the extent to which such contamination is prevalent in tissue block samples, we obtained and analyzed samples of paraffin blocks from hospitals in six major cities and found them to contain measurable concentrations of asbestos. Whether this asbestos contamination originated in the virgin wax or was a result of processing has not been established. This result, which has not been previously reported, raises significant concerns about the validity of analyses for asbestos in tissue embedded in paraffin. In particular, diagnoses in which the presence of asbestos in tissue samples is taken as being indicative of past asbestos exposure, especially for those cases in which no known exposure has occurred, and studies purporting to show migration of asbestos to other organs in the body following inhalation or ingestion of asbestos require critical reevaluation. The need for reevaluation is particularly acute if appropriate control blanks were not evaluated as part of the studies.}, } @article {pmid7551944, year = {1995}, author = {Rusch, VW}, title = {Clinical features and current treatment of diffuse malignant pleural mesothelioma.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {12 Suppl 2}, number = {}, pages = {S127-46}, doi = {10.1016/s0169-5002(10)80011-x}, pmid = {7551944}, issn = {0169-5002}, mesh = {Antineoplastic Agents/therapeutic use ; Asbestos/adverse effects ; Clinical Trials as Topic ; Combined Modality Therapy ; Humans ; Immunotherapy ; Lymphatic Metastasis ; Mesothelioma/diagnosis/epidemiology/*physiopathology/*therapy ; Neoplasm Staging ; Pleural Neoplasms/diagnosis/epidemiology/*physiopathology/*therapy ; Radiotherapy/methods ; Risk Factors ; Tomography, X-Ray Computed ; }, abstract = {Malignant pleural mesothelioma is an uncommon cancer for which the major risk factor is prior asbestos exposure. During the past decade, there has been progress in the diagnosis, staging and biology of mesothelioma. Treatment remains controversial and ranges from supportive care alone to aggressive multimodality therapy. Prospective clinical trials in carefully staged patients are needed to determine what approaches to treatment may confer a survival benefit.}, } @article {pmid7479364, year = {1995}, author = {Grellner, W and Staak, M}, title = {Multiple skeletal muscle metastases from malignant pleural mesothelioma.}, journal = {Pathology, research and practice}, volume = {191}, number = {5}, pages = {456-60; discussion 461-2}, doi = {10.1016/S0344-0338(11)80732-6}, pmid = {7479364}, issn = {0344-0338}, mesh = {Asbestos/analysis ; Asbestosis/metabolism/pathology ; Humans ; Male ; Mesothelioma/chemistry/*pathology ; Middle Aged ; Muscle, Skeletal/chemistry/*pathology ; Pleural Neoplasms/chemistry/*pathology ; Soft Tissue Neoplasms/chemistry/*pathology/*secondary ; }, abstract = {A 54-year-old male patient (occupational asbestos exposure over 27 years) died 2 years and 4 months after the diagnosis of malignant pleural mesothelioma of the right side, despite twice undergoing pleurectomy and radiotherapy. The autopsy revealed a locally advanced pleural mesothelioma of both sides involving the pericardium, heart, right diaphragm, liver and peritoneum. Disseminated metastases in numerous lymph nodes and a hematogenous metastatic spread into both lungs, the thyroid gland, peritoneum and skeletal musculature were found. The left temporal muscle and proximal limb skeletal muscles of the right upper arm and both thighs exhibited multiple metastases measuring up to 7 cm in diameter. Microscopically, a biphasic type of mesothelioma was detected. To our knowledge this is the first extensive case report on muscle metastases in malignant mesothelioma. Reviewing the literature, it is thought that in the presented case the long survival time of the patient and his protracted preterminal immobility could have contributed to the unusual formation of multiple skeletal muscle metastases.}, } @article {pmid7743507, year = {1995}, author = {Janssen, YM and Heintz, NH and Mossman, BT}, title = {Induction of c-fos and c-jun proto-oncogene expression by asbestos is ameliorated by N-acetyl-L-cysteine in mesothelial cells.}, journal = {Cancer research}, volume = {55}, number = {10}, pages = {2085-2089}, pmid = {7743507}, issn = {0008-5472}, support = {ES 06499/ES/NIEHS NIH HHS/United States ; HL 39469/HL/NHLBI NIH HHS/United States ; }, mesh = {Acetylcysteine/*pharmacology ; Asbestos, Crocidolite/*pharmacology ; Buthionine Sulfoximine ; Genes, fos ; Genes, jun ; Glutathione/*metabolism ; Humans ; Methionine Sulfoximine/analogs & derivatives/pharmacology ; Proto-Oncogene Mas ; Proto-Oncogene Proteins c-fos/*biosynthesis/drug effects ; Proto-Oncogene Proteins c-jun/*biosynthesis/drug effects ; RNA, Messenger/biosynthesis ; Superoxide Dismutase/metabolism ; }, abstract = {Asbestos fibers cause dose-dependent, persistent increases in mRNA levels of c-jun and c-fos proto-oncogenes in rat pleural mesothelial (RPM) cells, the progenitor cells of asbestos-induced mesothelioma (N. Heintz, Y. M. W. Janssen, and B. T. Mossman. Proc. Natl. Acad. Sci. USA, 90: 3299-3303, 1993). Here we report that addition of N-acetyl-L-cysteine decreases asbestos-mediated induction of c-fos and c-jun mRNA levels in a dose-dependent fashion. Exposure of RPM cells to asbestos causes depletion of total cellular glutathione, a response that can be abolished by pretreatment with N-acetyl-L-cysteine. Pretreatment of cells with buthionine sulfoximine, an agent which diminishes glutathione pools, increases the magnitude of induction of c-fos and c-jun mRNA by asbestos. To determine whether asbestos-induced effects on proto-oncogene expression could be attributed to extracellular generation of active oxygen species (AOS), RPM cells were exposed to H2O2 or xanthine and xanthine oxidase, a generating system of AOS. These oxidant stresses did not decrease cellular glutathione levels nor alter mRNA levels of c-fos or c-jun. However, increased mRNA levels of manganese-containing superoxide dismutase and heme oxygenase were observed, indicating that RPM cells respond to AOS by increased expression of genes encoding antioxidant enzymes. These data indicate that the signaling pathways leading to c-fos/c-jun proto-oncogene induction by asbestos are not triggered directly by formation of extracellular AOS. However, intracellular thiol levels appear to influence the expression of c-fos and c-jun, suggesting a redox-sensitive component in the signaling cascade which modulates gene expression of c-fos and c-jun by asbestos.}, } @article {pmid7739316, year = {1995}, author = {Weill, H and Hughes, JM}, title = {Mesothelioma.}, journal = {Lancet (London, England)}, volume = {345}, number = {8959}, pages = {1234}, pmid = {7739316}, issn = {0140-6736}, mesh = {Asbestos/*adverse effects ; Humans ; Mesothelioma/chemically induced/*epidemiology ; Occupational Diseases/chemically induced/epidemiology ; Occupational Exposure/*statistics & numerical data ; United Kingdom/epidemiology ; United States/epidemiology ; }, } @article {pmid7739315, year = {1995}, author = {Damhuis, RA and Planteydt, HT}, title = {Mesothelioma.}, journal = {Lancet (London, England)}, volume = {345}, number = {8959}, pages = {1233-1234}, pmid = {7739315}, issn = {0140-6736}, mesh = {Asbestos/*adverse effects ; Humans ; Incidence ; Lung Neoplasms/chemically induced/*epidemiology ; Mesothelioma/chemically induced/*epidemiology ; Netherlands/epidemiology ; Occupational Diseases/chemically induced/*epidemiology ; United Kingdom/epidemiology ; }, } @article {pmid7605458, year = {1995}, author = {De Vos Irvine, H}, title = {Mesothelioma.}, journal = {Lancet (London, England)}, volume = {345}, number = {8959}, pages = {1233}, pmid = {7605458}, issn = {0140-6736}, mesh = {Asbestos/*adverse effects ; Humans ; Lung Diseases/chemically induced/*epidemiology ; Mesothelioma/chemically induced/*epidemiology ; Occupational Diseases/chemically induced/*epidemiology ; Scotland/epidemiology ; }, } @article {pmid7742009, year = {1995}, author = {Fitzpatrick, DR and Peroni, DJ and Bielefeldt-Ohmann, H}, title = {The role of growth factors and cytokines in the tumorigenesis and immunobiology of malignant mesothelioma.}, journal = {American journal of respiratory cell and molecular biology}, volume = {12}, number = {5}, pages = {455-460}, doi = {10.1165/ajrcmb.12.5.7742009}, pmid = {7742009}, issn = {1044-1549}, mesh = {Cytokines/*physiology ; Growth Substances/*physiology ; Humans ; Interleukin-6/physiology ; Mesothelioma/pathology/*physiopathology ; Platelet-Derived Growth Factor/physiology ; Pleural Neoplasms/pathology/*physiopathology ; Receptors, Cytokine/physiology ; Transforming Growth Factor beta/physiology ; }, abstract = {Malignant mesothelioma (MM) is an asbestos-associated cancer that is increasing in incidence worldwide and is refractory to conventional therapy. MM cells are potent sources of a number of cytokines, some of which have recently been shown to be directly involved in the aggressive growth and spread of MM tumors. Emerging data also suggest involvement of MM-derived cytokines in systemic paraneoplastic syndromes including immunosuppression, thrombocytosis, cachexia, amyloidosis, and hypoglycemia. Additional characterization of the expression of cytokines and cytokine receptors in situ in MM tumors may provide a more complete picture of the autocrine and paracrine processes which occur in MM. Improved therapy of MM, particularly cytokine-based approaches, is likely to benefit from further elucidation of the patterns and regulation of cytokine expression associated with MM tumors.}, } @article {pmid7665001, year = {1995}, author = {Warheit, DB and Driscoll, KE and Oberdoerster, G and Walker, C and Kuschner, M and Hesterberg, TW}, title = {Contemporary issues in fiber toxicology.}, journal = {Fundamental and applied toxicology : official journal of the Society of Toxicology}, volume = {25}, number = {2}, pages = {171-183}, doi = {10.1006/faat.1995.1053}, pmid = {7665001}, issn = {0272-0590}, mesh = {Administration, Inhalation ; Animals ; Asbestos/adverse effects/chemistry/*toxicity ; Carbon/adverse effects/*toxicity ; *Carbon Compounds, Inorganic ; Cytokines/metabolism ; Disease Models, Animal ; *Glass ; Humans ; Inflammation/etiology ; Lung/*pathology ; Lung Neoplasms/*etiology/pathology ; Macrophages, Alveolar/physiology ; Mesothelioma/*etiology/pathology ; Microscopy, Electron, Scanning ; Silicon Compounds/adverse effects/*toxicity ; }, } @article {pmid7613813, year = {1995}, author = {Huncharek, M and Klassen, M and Christiani, D}, title = {Mesothelioma of the tunica vaginalis testis with possible occupational asbestos exposure.}, journal = {British journal of urology}, volume = {75}, number = {5}, pages = {679-680}, doi = {10.1111/j.1464-410x.1995.tb07437.x}, pmid = {7613813}, issn = {0007-1331}, mesh = {Asbestos/adverse effects ; Humans ; Male ; Mesothelioma/*pathology ; Middle Aged ; Occupational Diseases/*pathology ; Occupational Exposure/adverse effects ; Testicular Neoplasms/*pathology ; }, } @article {pmid7580104, year = {1995}, author = {Sturm, W and Menze, B and Krause, J and Thriene, B}, title = {Asbestos-related diseases and asbestos types used in the former GDR.}, journal = {Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie}, volume = {47}, number = {2-3}, pages = {173-178}, doi = {10.1016/S0940-2993(11)80310-6}, pmid = {7580104}, issn = {0940-2993}, mesh = {Asbestos/*adverse effects/chemistry ; Asbestos, Amphibole/adverse effects ; Asbestos, Serpentine/adverse effects ; Asbestosis/*epidemiology ; Carcinogens/adverse effects ; Germany, East/epidemiology ; Humans ; Laryngeal Neoplasms/chemically induced/epidemiology ; Lung Neoplasms/chemically induced/epidemiology ; Mesothelioma/chemically induced/epidemiology ; Occupational Diseases/*chemically induced/epidemiology ; }, abstract = {In the period from 1960 to 1990 about 1.4 million tonnes of asbestos were imported by the former German Democratic Republic (GDR) and mainly processed into asbestos-cement products for the building industry. The production was concentrated in the former counties of Magdeburg and Dresden. In the past, asbestos was primarily used as insulation and fire prevention material, etc. in the large-scale chemical industry. Chrysotile was predominantly imported from the former Soviet Union, partly from Canada. Very small amounts of amphiboles came from Mozambique, but they were not processed in the counties of Magdeburg and Halle. In the German Federal State of Saxony-Anhalt, approx. 600 asbestoses, almost 2,700 pleural changes caused by asbestos, 843 asbestos-induced mesotheliomas and 787 bronchial and laryngeal carcinomas caused by asbestos were recorded in the period from 1960 to 1990. A considerable percentage of the mesotheliomas are solely due to exposure to chrysotile asbestos.}, } @article {pmid7565290, year = {1995}, author = {Albin, M and Shefer, I and Magnani, C and Krstev, S}, title = {Asbestos and cancer.}, journal = {La Medicina del lavoro}, volume = {86}, number = {3}, pages = {259-262}, pmid = {7565290}, issn = {0025-7818}, mesh = {Asbestos/*adverse effects ; Case-Control Studies ; Europe/epidemiology ; Female ; Humans ; Incidence ; Lung Neoplasms/*epidemiology/*etiology ; Male ; Mesothelioma/*epidemiology/*etiology ; Occupational Diseases/*epidemiology ; *Occupational Exposure ; Risk Factors ; Sex Factors ; Smoking/adverse effects ; }, } @article {pmid7746180, year = {1995}, author = {Glasziou, P}, title = {Non-asbestos-related mesothelioma: chance, bias, or a real phenomenon?.}, journal = {The Medical journal of Australia}, volume = {162}, number = {8}, pages = {431-432}, doi = {10.5694/j.1326-5377.1995.tb139976.x}, pmid = {7746180}, issn = {0025-729X}, mesh = {Asbestos/*adverse effects ; Bias ; Confounding Factors, Epidemiologic ; Female ; Humans ; Male ; Mesothelioma/*etiology ; Occupational Exposure/*adverse effects ; }, } @article {pmid7746179, year = {1995}, author = {Gun, RT}, title = {Mesothelioma: is asbestos exposure the only cause?.}, journal = {The Medical journal of Australia}, volume = {162}, number = {8}, pages = {429-431}, pmid = {7746179}, issn = {0025-729X}, mesh = {*Asbestos/adverse effects ; Case-Control Studies ; Female ; Humans ; Incidence ; Male ; Mesothelioma/epidemiology/*etiology ; Middle Aged ; Occupational Exposure/adverse effects/*analysis ; Poisson Distribution ; Risk Factors ; Sex Factors ; }, abstract = {BACKGROUND: Although a causal association between mesothelioma and occupational exposure to asbestos is beyond dispute, nearly all population-based studies of mesothelioma have found some proportion of cases with no history of asbestos exposure.

DATA: Incidences of mesothelioma in men and women not occupationally exposed to asbestos for the period 1980-1985 were generated from: (i) estimates of occupational exposure to asbestos in the general male population, obtained from population-based controls in a case-control study of incident cancer in South Australia; and (ii) National Mesothelioma Surveillance Program data. The incidence in men not occupationally exposed was 8.5 per 1,000,000 person-years, compared with 2.6 per 1,000,000 person-years in women, a difference of 5.9 per 1,000,000 person-years (90% confidence interval, 4.8-7.2).

CONCLUSION: Mesothelioma without a history of asbestos exposure may be caused by asbestos in the general environment, but this fails to explain why such cases occur more commonly in men. Alternative explanations include the existence of another independent cause of mesothelioma, or of a co-factor which, combined with "environmental" levels of asbestos exposure, constitutes a sufficient cause. Such a risk factor is likely to be occupational, in which case mesothelioma may be expected to occur even after occupational asbestos exposures have been eliminated.}, } @article {pmid7793430, year = {1995}, author = {Schepers, GW}, title = {Chronology of asbestos cancer discoveries: experimental studies of the Saranac Laboratory.}, journal = {American journal of industrial medicine}, volume = {27}, number = {4}, pages = {593-606}, doi = {10.1002/ajim.4700270413}, pmid = {7793430}, issn = {0271-3586}, mesh = {Animals ; Asbestos/adverse effects/*history ; Asbestos, Serpentine/adverse effects ; History, 20th Century ; Humans ; Lung Neoplasms/etiology/*history/pathology ; Medical Oncology/history ; Mesothelioma/etiology/*history/pathology ; Neoplasms, Experimental/*history ; United States ; }, abstract = {This commentary challenges a recently published perception that Dr. Le Roy Upson Gardner had not actually discovered in 1942 that inhaled chrysotile fibers could induce malignant neoplasia in mice. The handwritten laboratory notes and some of Dr. Gardner's slides have recently been found. They verify that the tumors he saw in the mice included truly malignant neoplasms. Gardner had by then also accumulated 11 cases of human lung cancer (two mesotheliomas) derived from Quebec asbestos miners and millers. An inhalation study designed by Dr. Gardner and conducted between 1951 and 1954, using cancer-insusceptible mice, yielded neoplasia risk ratio of 5.7 compared with control animals. The studies also showed that the primary effect of chrysotile is to cause epithelial proliferation in alveoli adjacent to bronchioles. Chrysotile type asbestos bodies were shown to remain only transiently ferruginous, but even though invisible in direct light they can be visualized at high magnification through use of phase contrast and polarized light micrography.}, } @article {pmid7793429, year = {1995}, author = {Dufresne, A and Harrigan, M and Massé, S and Bégin, R}, title = {Fibers in lung tissues of mesothelioma cases among miners and millers of the township of Asbestos, Quebec.}, journal = {American journal of industrial medicine}, volume = {27}, number = {4}, pages = {581-592}, doi = {10.1002/ajim.4700270412}, pmid = {7793429}, issn = {0271-3586}, mesh = {Aged ; Asbestos/*adverse effects/analysis ; Asbestos, Amosite/analysis ; Asbestos, Amphibole/analysis ; Asbestos, Crocidolite/analysis ; Asbestos, Serpentine/analysis ; Culture Techniques ; Humans ; Lung Neoplasms/chemistry/etiology/*pathology ; Male ; Mesothelioma/chemistry/etiology/*pathology ; Middle Aged ; Mining ; Occupational Diseases/etiology/*pathology ; Quebec ; Textile Industry ; }, abstract = {Twenty cases of mesothelioma among miners of the township of Asbestos, Quebec, Canada, have been reported. To further explore the mineral characteristics of various fibrous material, we studied the fibrous inorganic content of postmortem lung tissues of 12 of 20 available cases. In each case, we measured concentrations of chrysotile, amosite, crocidolite, tremolite, talc-anthophyllite, and other fibrous minerals. The average diameter, length, and length-to-diameter ratio of each type of fiber were also calculated. For total fibers > 5 microns, we found > 1,000 asbestos fibers per mg tissue (f/mg) in all cases; tremolite was above 1,000 f/mg in 8 cases, chrysotile in 6 cases, crocidolite in 4 cases, and talc anthophyllite in 5 cases. Among cases with asbestos fibers, the tremolite count was highest in 7 cases, chrysotile in 3 cases, and crocidolite in 2 cases. The geometric mean concentrations of fibers > or = 5 microns were in the following decreasing order: tremolite > crocidolite > chrysotile > other fibers > talc-anthophyllite > amosite. For total fibers < 5 microns, we found > 1,000 fibers per mg tissue (f/mg) in all cases; tremolite was above 1,000 f/mg in 12 cases, chrysotile in 8 cases, crocidolite in 7 cases, and talc-anthophyllite in 6 cases. Tremolite was highest in 8 cases, chrysotile in 2 cases, and crocidolite and amosite in 2 cases. The geometric mean concentrations of fibers < 5 microns were in the following decreasing order: tremolite > other fibers > chrysotile > crocidolite > talc-anthophyllite > amosite. We conclude, on the basis of the lung burden analyses of 12 mesothelioma cases from the Asbestos township of Quebec, that the imported amphibole (crocidolite and amosite) were the dominant fibers retained in the lung tissue in 2/12 cases. In 10/12 cases, fibers from the mine site (chrysotile and tremolite) were found at highest counts; tremolite was clearly the highest in 6, chrysotile in 2, and 2 cases had about the same counts for tremolite and chrysotile. If a relation of fiber burden-causality of mesothelioma is accepted, mesothelioma would be likely caused by amphibole contamination of the plant in 2/12 cases and by the mineral fibers (tremolite and chrysotile) from the mine site in the 10 other cases.}, } @article {pmid7793428, year = {1995}, author = {Andersson, E and Torén, K}, title = {Pleural mesotheliomas are underreported as occupational cancer in Sweden.}, journal = {American journal of industrial medicine}, volume = {27}, number = {4}, pages = {577-580}, doi = {10.1002/ajim.4700270411}, pmid = {7793428}, issn = {0271-3586}, mesh = {Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Female ; Humans ; Lung Neoplasms/*epidemiology/etiology ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Diseases/*epidemiology/etiology ; Pleural Neoplasms/*epidemiology/etiology ; Registries/statistics & numerical data ; Sex Distribution ; Sweden/epidemiology ; }, abstract = {The aim of this study was to estimate to what degree malignant pleural mesotheliomas were reported as occupational cancers. The study included all malignant pleural mesotheliomas (n = 210) found in the Cancer Registry 1980-1989 from four Swedish counties. Whether or not a case was reported as occupational cancer was found in the Swedish Register of Reported Occupational Diseases. To evaluate the presence of exposure histories, the chest department files for 58 mesotheliomas from one county were reviewed. The reporting was low, with only 75 mesotheliomas (36%) reported. All the cases were men, and for the men, the reporting frequency was 42%. The reporting was significantly lower for the last part of the decade than for the first part. The reporting frequency decreased with age. In the review of the chest department files, an exposure history was found in 93% of the reported cases and in 47% of the unreported cases. It is concluded that physicians must give more priority to exposure histories in patients with pleural mesotheliomas.}, } @article {pmid7793427, year = {1995}, author = {Crosignani, P and Forastiere, F and Petrelli, G and Merler, E and Chellini, E and Pupp, N and Donelli, S and Magarotto, G and Rotondo, E and Perucci, C}, title = {Malignant mesothelioma in thermoelectric power plant workers in Italy.}, journal = {American journal of industrial medicine}, volume = {27}, number = {4}, pages = {573-576}, doi = {10.1002/ajim.4700270410}, pmid = {7793427}, issn = {0271-3586}, mesh = {Aged ; Asbestos/*adverse effects ; Cohort Studies ; Humans ; Italy/epidemiology ; Lung Neoplasms/epidemiology/*etiology ; Male ; Mesothelioma/epidemiology/*etiology ; Middle Aged ; Occupational Diseases/epidemiology/*etiology ; *Power Plants ; }, abstract = {Asbestos has been widely used in Italian thermoelectric power plants and instances of exposure to workers have been documented in a variety of jobs. Preventive measures were put into effect only in the late 1970s. We report here on four mesothelioma cases among workers of three Italian power plants where cohort studies were carried out, and on three additional cases recorded by a systematic survey carried out on this neoplasm in Tuscany. When the data of the cohorts sources are merged, a significant excess of lung cancer is also evident. Even without a quantitative assessment of exposure, this report shows the importance of asbestos risk in thermal power plants. The risk appears not to be restricted to any particular category of workers.}, } @article {pmid7793421, year = {1995}, author = {Stern, F and Schulte, P and Sweeney, MH and Fingerhut, M and Vossenas, P and Burkhardt, G and Kornak, MF}, title = {Proportionate mortality among construction laborers.}, journal = {American journal of industrial medicine}, volume = {27}, number = {4}, pages = {485-509}, doi = {10.1002/ajim.4700270404}, pmid = {7793421}, issn = {0271-3586}, mesh = {Accidents, Occupational/*mortality ; Adult ; Age Distribution ; Cause of Death ; Confidence Intervals ; Construction Materials ; Female ; Hazardous Substances ; Humans ; Incidence ; Labor Unions ; Male ; Neoplasms/epidemiology/*mortality ; Occupational Diseases/epidemiology/*mortality ; Risk Factors ; Sex Distribution ; United States/epidemiology ; }, abstract = {This report presents the results of proportionate mortality ratio (PMR) analyses and proportionate cancer mortality ratio (PCMR) analyses among the 11,685 members of the Laborers' International Union of North America (LIUNA), who died between 1985-1988, using U.S. proportionate mortality rates as the comparison population. Statistically significant elevated mortality risks were observed for all malignant neoplasms (N = 3285, PMR = 1.13, CI = 1.09-1.17), as well as for site-specific neoplasms of the lung (N = 1208, PCMR = 1.06, CI = 1.00-1.12), stomach (N = 170, PCMR = 1.44, CI = 1.23-1.68), and thyroid gland (N = 10, PCMR = 2.24, CI = 1.07-4.12). The PCMRs for these malignant neoplasms were elevated among both white and non-white males, regardless of length of union membership, in most 10-year categories of age at death above 40 and for the three largest LIUNA regions examined. The study also observed 20 mesothelioma deaths, which indicated that some LIUNA members had been previously exposed to asbestos. Statistically significant elevated risks were also observed for deaths from transportation injuries (N = 448, PMR = 1.37, CI = 1.25-1.51), falls (N = 85, PMR = 1.34, CI = 1.07-1.66), and other types of injuries (N = 245, PMR = 1.61, CI = 1.42-1.83). The deaths due to injuries were most often observed among those members who had the shortest amount of time within the union, were younger, and first entered the union after 1955. This is the first study that has examined the general mortality experience limited to construction laborers only (Bureau of Census code 869).}, } @article {pmid7664867, year = {1995}, author = {Garlepp, MJ and Leong, CC}, title = {Biological and immunological aspects of malignant mesothelioma.}, journal = {The European respiratory journal}, volume = {8}, number = {4}, pages = {643-650}, pmid = {7664867}, issn = {0903-1936}, mesh = {Animals ; Asbestos/adverse effects ; Gene Transfer Techniques ; Genes, Tumor Suppressor ; Growth Substances/metabolism ; Humans ; Lymphocyte Activation ; *Mesothelioma/genetics/immunology ; Oncogenes ; *Peritoneal Neoplasms/genetics/immunology ; *Pleural Neoplasms/genetics/immunology ; T-Lymphocytes ; Transfection ; Tumor Cells, Cultured ; }, abstract = {Malignant mesothelioma (MM) is an aggressive tumour, which is strongly associated with previous asbestos exposure and is resistant to all conventional anticancer therapies. An understanding of the biological properties of MM may provide insights into useful therapeutic strategies, and MM cell lines and animal models have been major contributors to our current knowledge of this tumour. Although karyotypic abnormalities are frequent, there is no clear evidence of a mesothelioma-specific chromosomal aberration. Similarly, there is no evidence of activation or over-expression of a known oncogene, or of the inactivation of currently identified tumour suppressor genes. A number of growth factors, including platelet derived growth factors A and B (PDGF-A and -B), insulin-like growth factor I and transforming growth factor-beta (TGF-beta), and some of their receptors, have been reported to be expressed by MM cells, and each has the potential to play a role as a growth stimulant for MM or to modify immune responses to the tumour. Some data support an autocrine role for PDGF-A. MM cell lines are susceptible to lysis by a variety of immune effector cells, and their growth can often be inhibited by cytokines. The possibility of stimulating an immune response to MM by genetic manipulation of the tumour cells has been investigated using a murine model. The data so far suggest that transfection of allogeneic class I major histocompatibility complex genes or syngeneic class II genes alone is unlikely to induce protective immunity.(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid7597255, year = {1995}, author = {Berman, DW and Crump, KS and Chatfield, EJ and Davis, JM and Jones, AD}, title = {The sizes, shapes, and mineralogy of asbestos structures that induce lung tumors or mesothelioma in AF/HAN rats following inhalation.}, journal = {Risk analysis : an official publication of the Society for Risk Analysis}, volume = {15}, number = {2}, pages = {181-195}, doi = {10.1111/j.1539-6924.1995.tb00312.x}, pmid = {7597255}, issn = {0272-4332}, mesh = {Administration, Inhalation ; Animals ; Asbestos/*adverse effects/*chemistry/classification ; Asbestos, Amosite/adverse effects/chemistry ; Asbestos, Crocidolite/adverse effects/chemistry ; Asbestos, Serpentine/adverse effects/chemistry ; Dust/adverse effects ; Environmental Exposure/adverse effects ; Incidence ; Information Systems ; Likelihood Functions ; Lung Neoplasms/*etiology ; Male ; Mesothelioma/*etiology ; Microscopy, Electron ; Multivariate Analysis ; Rats ; Rats, Inbred Strains ; Risk Factors ; Surface Properties ; }, abstract = {Data from inhalation studies in which AF/HAN rats were exposed to nine different types of asbestos dusts (in 13 separate experiments) are employed in a statistical analysis to determine if a measure of asbestos exposure (expressed as concentrations of structures with defined sizes, shapes and mineralogy) can be identified that satisfactorily predicts the observed lung tumor or mesothelioma incidence in the experiments. Due to limitations in the characterization of asbestos structures in the original studies, new exposure measures were developed from samples of the original dusts that were re-generated and analyzed by transmission electron microscopy using a direct transfer technique. This analysis provided detailed information on the mineralogy (i.e., chrysotile, amosite, crocidolite or tremolite), type (i.e., fiber, bundle, cluster, or matrix), size (length and width) and complexity (i.e., number of identifiable components of a cluster or matrix) of each individual structure. No univariate measure of exposure was found to provide an adequate description of the lung tumor responses observed among the inhalation studies, although the measure most highly correlated with tumor incidence is the concentration of structures > or = 20 microns in length. Multivariate measures of exposure were identified that do adequately describe the lung tumor responses. Structures contributing to lung tumor risk appear to be long (> or = 5 microns) thin (0.4 microns) fibers and bundles, with a possible contribution by long and very thick (> or = 5 microns) complex clusters and matrices. Potency appears to increase with increasing length, with structures longer than 40 microns being about 500 times more potent than structures between 5 and 40 microns in length. Structures < 5 microns in length do not appear to make any contribution to lung tumor risk. This analysis did not find a difference in the potency of chrysotile and amphibole toward the induction of lung tumors. However, mineralogy appears to be important in the induction of mesothelioma with chrysotile being less potent than amphibole.}, } @article {pmid7896462, year = {1995}, author = {Damhuis, RA and Planteydt, HT}, title = {Trends in incidence of pleural mesothelioma in the Rotterdam area.}, journal = {International journal of cancer}, volume = {60}, number = {6}, pages = {883}, doi = {10.1002/ijc.2910600627}, pmid = {7896462}, issn = {0020-7136}, mesh = {Aged ; Asbestos/*adverse effects ; Female ; Humans ; Incidence ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Netherlands/epidemiology ; Pleural Neoplasms/*epidemiology/etiology ; }, } @article {pmid7892557, year = {1995}, author = {Seaton, A}, title = {[Asbestos: past, present and future].}, journal = {Schweizerische medizinische Wochenschrift}, volume = {125}, number = {10}, pages = {453-457}, pmid = {7892557}, issn = {0036-7672}, mesh = {Asbestos/*adverse effects ; Asbestosis/*etiology ; Construction Materials/adverse effects ; *Environmental Exposure ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/etiology ; Occupational Exposure ; Risk Factors ; }, abstract = {Owing to its particular properties asbestos has been widely used for the production of insulating material, for fire proofing, and for strengthening to other materials such as cements and plastics, and thus the story of this mineral was one of progressive commercial success until the middle of this century. However, serious health hazards were realized early: around the turn of the century a progressive form of diffuse fibrosis (asbestosis) in asbestos workers was observed and in 1950 an excess risk of lung cancer, while in 1960 the causal relationship between asbestos and mesothelioma were confirmed. In view of the known potential risks of asbestos and its widespread use in the building industry, more recently asbestos has caused considerable public concern and anxiety. Based on numerous experimental and epidemiological observations, present knowledge of the pathogenic effects of asbestos is sufficient for a number of broad conclusions to be drawn. (1) The amphibole types of asbestos are too dangerous for use as industrial material, and should be banned. (2) Chrysotile can probably be used safely if there is strict control of the workers' dust exposure. (3) It is very unlikely that the general public is at any measurable risk from asbestos in buildings. Exceptions are people working regularly on maintenance tasks involving removing or cutting of asbestos in buildings; such people are properly classified as asbestos workers and should be protected accordingly.(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid7776771, year = {1995}, author = {Peto, J and Hodgson, JT and Matthews, FE and Jones, JR}, title = {Continuing increase in mesothelioma mortality in Britain.}, journal = {Lancet (London, England)}, volume = {345}, number = {8949}, pages = {535-539}, doi = {10.1016/s0140-6736(95)90462-x}, pmid = {7776771}, issn = {0140-6736}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Cohort Studies ; Death Certificates ; Female ; Forecasting ; Humans ; Male ; Mesothelioma/diagnosis/etiology/*mortality ; Middle Aged ; Mortality/trends ; Occupational Exposure/adverse effects ; Occupations ; Peritoneal Neoplasms/diagnosis/etiology/mortality ; Pleural Neoplasms/diagnosis/etiology/mortality ; Risk ; United Kingdom/epidemiology ; }, abstract = {Mesothelioma is closely related to exposure to asbestos, and mesothelioma mortality can be taken as an index of past exposure to asbestos in the population. We analysed mesothelioma mortality since 1968 to assess the current state of the mesothelioma epidemic, and to predict its future course. We found that rates of mesothelioma in men formed a clear pattern defined by age and date of birth. Rates rose steeply with age showing a very similar pattern in all five-year birth cohorts. By date of birth, rates increased from mid-1893 to mid-1948, and then fell. Relative to the 1943-48 cohort, the risk for the 1948-53 cohort is 0.79 and for the 1953-58 cohort 0.48. Despite these falls, if the age profile of rates for these cohorts follows the pattern of past cohorts, their predicted lifetime mesothelioma risks will be 1.3%, 1.0%, and 0.6%. Combining projections for all cohorts results in a peak of annual male mesothelioma deaths in about the year 2020 of between 2700 and 3300 deaths. If diagnostic trend is responsible for a 20% growth in recorded cases every 5 years--an extreme but arguable case--and if this trend has now ceased, the peak of annual male deaths will be reduced to 1300, reached around the year 2010. Analysis of occupations recorded on death certificates indicate that building workers, especially plumbers and gas fitters, carpenters and electricians are the largest high-risk group. These data indicate that mesothelioma deaths will continue to increase for at least 15 and more likely 25 years. For the worst affected cohorts--men born in the 1940s--mesothelioma may account for around 1% of all deaths. Asbestos exposure at work in construction and building maintenance will account for a large proportion of these deaths, and it is important that such workers should be aware of the risks and take appropriate precautions.}, } @article {pmid9101229, year = {1995}, author = {Kinnula, VL and Raivio, KO and Linnainmaa, K and Ekman, A and Klockars, M}, title = {Neutrophil and asbestos fiber-induced cytotoxicity in cultured human mesothelial and bronchial epithelial cells.}, journal = {Free radical biology & medicine}, volume = {18}, number = {3}, pages = {391-399}, doi = {10.1016/0891-5849(94)00149-e}, pmid = {9101229}, issn = {0891-5849}, mesh = {Adenine Nucleotides/metabolism ; Antioxidants/pharmacology ; Asbestos, Amosite/*toxicity ; Bronchi/cytology/drug effects/metabolism ; Cell Death/drug effects ; Cell Line, Transformed ; Epithelial Cells ; Epithelium/drug effects/metabolism ; Free Radicals/metabolism ; Humans ; Hydrogen Peroxide/toxicity ; Inflammation/etiology ; L-Lactate Dehydrogenase/metabolism ; Luminescent Measurements ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Neutrophils/*drug effects/metabolism ; Pleura/cytology/drug effects/metabolism ; Reactive Oxygen Species/metabolism ; }, abstract = {This study investigates reactive oxygen species generation and oxidant-related cytotoxicity induced by amosite asbestos fibers and polymorphonuclear leucocytes (PMNs) in human mesothelial cells and human bronchial epithelial cells in vitro. Transformed human pleural mesothelial cells (MET 5A) and bronchial epithelial cells (BEAS 2B) were treated with amosite (2 micrograms/cm2) for 48 h. After 24 h of incubation, the cells were exposed for 1 h to nonactivated or amosite (50 micrograms) activated PMNs, washed, and incubated for another 23 h. Reactive oxygen species generation by the PMNs and the target cells was measured by chemiluminescence. Cell injury was assessed by cellular adenine nucleotide depletion, extracellular release of nucleotides, and lactate dehydrogenase (LDH). Amosite-activated (but also to a lesser degree nonactivated) PMNs released substantial amounts of reactive oxygen metabolites, whereas the chemiluminescence of amosite-exposed mesothelial cells and epithelial cells did not differ from the background. Amosite treatment (48 h) of the target cells did not change intracellular adenine nucleotides (ATP, ADP, AMP) or nucleotide catabolite products (xanthine, hypoxanthine, and uric acid). When the target cells were exposed to nonactivated PMNs, significant adenine nucleotide depletion and nucleotide catabolite accumulation was observed in mesothelial cells only. In separate experiments, when the target cells were exposed to amosite-activated PMNs, the target cell injury was further potentiated compared with the amosite treatment alone or exposure to nonactivated PMNs. In conclusion, this study suggests the importance of inflammatory cell-derived free radicals in the development of amosite-induced mesothelial cell injury.}, } @article {pmid7789485, year = {1995}, author = {Shijubo, N and Honda, Y and Fujishima, T and Takahashi, H and Kodama, T and Kuroki, Y and Akino, T and Abe, S}, title = {Lung surfactant protein-A and carcinoembryonic antigen in pleural effusions due to lung adenocarcinoma and malignant mesothelioma.}, journal = {The European respiratory journal}, volume = {8}, number = {3}, pages = {403-406}, doi = {10.1183/09031936.95.08030403}, pmid = {7789485}, issn = {0903-1936}, mesh = {Adenocarcinoma/complications/*diagnosis ; Asbestos/adverse effects ; Biomarkers, Tumor/*analysis ; Carcinoembryonic Antigen/*analysis ; Diagnosis, Differential ; Enzyme-Linked Immunosorbent Assay ; Glycoproteins/*analysis ; Humans ; Lung Neoplasms/complications/*diagnosis ; Mesothelioma/complications/*diagnosis ; Pleural Effusion, Malignant/*chemistry/etiology ; Proteolipids/*analysis ; Pulmonary Surfactant-Associated Protein A ; Pulmonary Surfactant-Associated Proteins ; Pulmonary Surfactants/*analysis ; }, abstract = {Lung surfactant protein-A (SP-A) is a major phospholipid-associated glycoprotein in surfactant, and is a useful immunohistochemical marker for lung adenocarcinoma. Carcinoembryonic antigen (CEA) has not been immunohistochemically detected in mesothelioma. In pleural effusions due to malignant mesothelioma, very low concentrations of SP-A and CEA can be expected. We studied the value of combined determinations of CEA and SP-A in pleural fluid to distinguish between lung adenocarcinoma and mesothelioma. SP-A and CEA concentrations were measured in pleural effusions from 78 patients with lung adenocarcinoma and 10 with malignant mesothelioma. SP-A concentrations in pleural effusions due to lung adenocarcinoma and mesothelioma were 516 +/- 140 and 16.9 +/- 3.6 ng.ml-1 (mean +/- SEM), respectively. CEA concentrations in pleural effusions due to lung adenocarcinoma and mesothelioma were 239 +/- 92.4 and 1.7 +/- 0.3 ng.ml-1, respectively. SP-A values did not exceed 100 ng.ml-1 in any of 10 mesotheliomas, whilst in 37 of 78 lung adenocarcinomas they did. CEA values did not exceed 10 ng.ml-1 in any of 10 mesotheliomas, whilst in 53 of 78 lung adenocarcinomas they did. Increased values of SP-A and/or CEA were found in pleural effusions from 67 of 78 lung adenocarcinomas. It is concluded that a combination of CEA and SP-A assays in pleural effusions will be helpful for discriminating lung adenocarcinoma from mesothelioma.}, } @article {pmid7768228, year = {1995}, author = {Dopp, E and Saedler, J and Stopper, H and Weiss, DG and Schiffmann, D}, title = {Mitotic disturbances and micronucleus induction in Syrian hamster embryo fibroblast cells caused by asbestos fibers.}, journal = {Environmental health perspectives}, volume = {103}, number = {3}, pages = {268-271}, pmid = {7768228}, issn = {0091-6765}, mesh = {Animals ; Asbestos/*adverse effects ; Cells, Cultured ; Cricetinae ; Fibroblasts ; Mesocricetus ; *Micronuclei, Chromosome-Defective ; Micronucleus Tests ; *Mitosis ; Time Factors ; }, abstract = {Asbestos and other mineral fibers have long been known to induce lung cancer and mesothelioma. However, the primary mechanisms of fiber-induced carcinogenesis still remain unclear. We investigated the occurrence of mitotic disturbances induced by asbestos (amosite, crocidolite, chrysotile) in an in vitro approach using Syrian hamster embryo (SHE) fibroblast cells. The following endpoints were investigated: micronucleus formation as a result of mitotic disturbances and characterization of the induced micronucleus population by kinetochore staining and visualization of the spindle apparatus. Supravital UV-microscopy was used to analyze changes in interphase chromatin structure, impaired chromatid separation, and blocked cytokinesis. All three asbestos fiber types induced a high frequency of micronucleus formation in SHE cells (> 200/2000 cells) in a dose-dependent manner (0.1-5.0 micrograms/cm2), with a maximum between 48 hr and 66 hr exposure time. At higher concentrations (more than 5.0 micrograms/cm2) the micronucleus formation decreased again as a result of increased toxicity. Kinetochore staining of micronuclei revealed that 48 +/- 2% of asbestos-induced micronuclei reacted positively with CREST (antikinetochore) serum. Furthermore, spindle apparatus deformations occurred in cells with disturbed metaphases and anaphases, while the spindle fiber morphology appeared unchanged. Our results show that asbestos fibers may cause both loss and breakage of chromosomes in the absence of direct interaction with spindle fibers.}, } @article {pmid7747748, year = {1995}, author = {Upton, AC and Shaikh, RA}, title = {Asbestos exposures in public and commercial buildings.}, journal = {American journal of industrial medicine}, volume = {27}, number = {3}, pages = {433-7; discussion 439-41}, doi = {10.1002/ajim.4700270311}, pmid = {7747748}, issn = {0271-3586}, mesh = {Animals ; Asbestos/*adverse effects ; Child ; *Construction Materials ; *Environmental Exposure ; Female ; Humans ; Lung Neoplasms/etiology ; Male ; Mesothelioma/etiology ; *Public Health ; Risk Factors ; }, } @article {pmid7742058, year = {1995}, author = {Romero Arauzo, MJ and Taxonera Samsó, C and Ciriza de los Ríos, C and Díez Ordoñez, MZ and Díaz-Rubio, M and Lopez Asenjo, JA}, title = {[Recurrent ascites in peritoneal mesothelioma. Its diagnostic and therapeutic management].}, journal = {Revista espanola de enfermedades digestivas}, volume = {87}, number = {3}, pages = {263-266}, pmid = {7742058}, issn = {1130-0108}, mesh = {Adenocarcinoma/diagnosis ; Ascites/*diagnosis/etiology/therapy ; Combined Modality Therapy ; Diagnosis, Differential ; Humans ; Male ; Mesothelioma/complications/*diagnosis/therapy ; Middle Aged ; Neoplasms, Unknown Primary/diagnosis ; Peritoneal Neoplasms/complications/*diagnosis/therapy ; Recurrence ; }, abstract = {Peritoneal mesothelioma is an uncommon neoplasm often related to previous asbestos exposure. It is necessary to exclude other secondary peritoneal neoplasm. The application of immunohistochemical analysis in the biopsy sample is important for establishing an accurate diagnosis. We report the case of a peritoneal mesothelioma that started as a haemorrhagic ascites. After laparotomy, the initial diagnosis was peritoneal carcinomatosis from adenocarcinoma of unknown origin. The diagnosis was obtained by using immunohistochemical analysis: vimentin and keratine antibodies were positive and leu M1, antibodies were negative. The interest of our case resides in the difficulty for obtaining the diagnosis and the complicate management of refractory ascites. Our patient required intraperitoneal 5-fluorouracil for controlling the ascites.}, } @article {pmid7619198, year = {1995}, author = {Schneider, J and Woitowitz, HJ}, title = {[Asbestos-related mesotheliomas in housewives from indoor air pollution].}, journal = {Zentralblatt fur Hygiene und Umweltmedizin = International journal of hygiene and environmental medicine}, volume = {196}, number = {6}, pages = {495-503}, pmid = {7619198}, issn = {0934-8859}, mesh = {Aged ; *Air Pollution, Indoor ; Asbestos/*adverse effects ; Clothing ; Female ; *Household Work ; Humans ; Male ; Mesothelioma/*etiology ; Middle Aged ; *Women ; }, abstract = {We report five cases of pleural mesothelioma in housewives, that are attributed to inhalative household-contact with asbestos. An occupational history of asbestos exposure could not be revealed. A causal relationship between the fatal disease and the inhalative house-hold-contact with asbestos was established based on the cleaning of asbestos contaminated work-clothes of the husbands.}, } @article {pmid7584666, year = {1995}, author = {Bielefeldt-Ohmann, H and Fitzpatrick, DR and Marzo, AL and Jarnicki, AG and Musk, AW and Robinson, BW}, title = {Potential for interferon-alpha-based therapy in mesothelioma: assessment in a murine model.}, journal = {Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research}, volume = {15}, number = {3}, pages = {213-223}, doi = {10.1089/jir.1995.15.213}, pmid = {7584666}, issn = {1079-9907}, mesh = {Adjuvants, Immunologic/therapeutic use ; Animals ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Carotenoids/administration & dosage/therapeutic use ; Eflornithine/administration & dosage/therapeutic use ; Female ; Interferon Type I/administration & dosage/*therapeutic use ; Lymphocytes, Tumor-Infiltrating/drug effects/immunology ; Macrophages/drug effects/immunology ; Mesothelioma/genetics/immunology/*therapy ; Mice ; Mice, Inbred CBA ; Mice, Inbred Strains ; RNA, Messenger/biosynthesis ; Recombinant Proteins ; Transforming Growth Factor beta/metabolism ; Tumor Cells, Cultured ; beta Carotene ; }, abstract = {Malignant mesothelioma is an aggressive tumor, usually induced by asbestos exposure, that has a poor prognosis and is unresponsive to conventional therapy. The present study was aimed at assessing the potential for interferon-alpha (IFN-alpha)-based therapies in a murine model for malignant mesothelioma. The effect of recombinant human IFN-alpha B/D on tumor growth, alone and in combination with either of two immunomodulatory and antiproliferative agents beta-carotene or alpha-difluoromethylornithine (DFMO), was assessed. The data suggest that IFN-alpha treatment is most efficacious when commenced early in tumor development. Combination of IFN-alpha with either DFMO or dietary beta-carotene supplementation improved the effect of an otherwise suboptimal IFN-alpha therapy regimen. Both IFN-alpha and beta-carotene had in vivo stimulatory effects on immune cells, perhaps indirectly by inhibiting TGF-beta generation. The immunomodulatory effects may contribute, at least in part, to the positive antitumor and clinical activities of the treatments in this model.}, } @article {pmid7547118, year = {1995}, author = {Pitrelli, N and Di Bartolomeo, N and Grossi, S and Innocenti, P and Pizzicannella, G}, title = {[Peritoneal mesothelioma].}, journal = {Il Giornale di chirurgia}, volume = {16}, number = {3}, pages = {100-102}, pmid = {7547118}, issn = {0391-9005}, mesh = {Diagnosis, Differential ; Humans ; Male ; *Mesothelioma/diagnosis/pathology ; Middle Aged ; *Peritoneal Neoplasms/diagnosis/pathology ; Peritoneum/pathology ; }, abstract = {Peritoneal mesothelioma is a quite rare tumor with an incidence of one or two cases per million inhabitants; approximately in the 30-45% of the cases diagnosed it is associated with the corresponding pleural mesothelioma. A predisposing factor is a previous occupational exposure to materials containing asbestos. Clinical symptomatology and instrumental findings may be confusing. Diagnosis is often possible only after direct vision and histologic examination during laparoscopy or laparotomy but it is always tardy, whereas therapy is still unsuccessful. Surgical excision and radiotherapy are less effective than intraperitoneal chemotherapy which seems to lengthen the average survival rate.}, } @article {pmid7900131, year = {1995}, author = {Mowé, G and Tellnes, G and Andersen, A}, title = {[Malignant pleural mesothelioma in Norway 1960-1992].}, journal = {Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke}, volume = {115}, number = {6}, pages = {706-709}, pmid = {7900131}, issn = {0029-2001}, mesh = {Adult ; Disease Notification ; Female ; Humans ; Incidence ; Male ; Mesothelioma/*epidemiology ; Norway/epidemiology ; Occupational Diseases/*epidemiology ; Pleural Neoplasms/*epidemiology ; Registries ; }, abstract = {The incidence of malignant pleural mesothelioma among men in Norway increased about eightfold from 1960 to 1992. A similar rise in incidence has been observed in many countries with large consumption of asbestos during the last 50 years. The causal relationship between malignant mesothelioma and previous exposure to asbestos is well established. The investigation shows incomplete notification to the Labour Inspection as compared with the number of cases recorded by the Cancer Registry. Patients may therefore lose compensation both from the National Insurance Administration and as authorized by the new Occupational Injury Insurance Act of 1990. Asbestos was prohibited in Norway in 1985. Owing to the long latency time, about 30-40 years, the rise in incidence will probably continue for the next 20 years or more. Strict preventive precautions are important in order to prevent a "third wave" of asbestos-related diseases in the future.}, } @article {pmid7710525, year = {1995}, author = {McDonald, JC and McDonald, AD}, title = {Chrysotile, tremolite, and mesothelioma.}, journal = {Science (New York, N.Y.)}, volume = {267}, number = {5199}, pages = {776-777}, doi = {10.1126/science.267.5199.776-a}, pmid = {7710525}, issn = {0036-8075}, mesh = {Asbestos, Amphibole/*adverse effects ; Asbestos, Serpentine/*adverse effects ; Cohort Studies ; Humans ; Lung Neoplasms/*etiology ; Male ; Mesothelioma/*etiology ; *Mining ; Occupational Diseases/*etiology ; Occupational Exposure ; Quebec ; Time Factors ; }, } @article {pmid7756687, year = {1995}, author = {Hand, A and Pelin, K and Mattson, K and Linnainmaa, K}, title = {Interferon (IFN)-alpha and IFN-gamma in combination with methotrexate: in vitro sensitivity studies in four human mesothelioma cell lines.}, journal = {Anti-cancer drugs}, volume = {6}, number = {1}, pages = {77-82}, doi = {10.1097/00001813-199502000-00009}, pmid = {7756687}, issn = {0959-4973}, mesh = {Drug Interactions ; Humans ; Intercalating Agents/pharmacology ; Interferon-alpha/*pharmacology ; Interferon-beta/pharmacology ; Interferon-gamma/pharmacology ; Mesothelioma/drug therapy/pathology/*therapy ; Methotrexate/pharmacology ; Mitoxantrone/pharmacology ; Recombinant Proteins ; Tumor Cells, Cultured/drug effects ; }, abstract = {Mesothelioma is a malignant tumor of the serous surfaces in the thorax and abdomen, which has proved exceptionally resistant to treatment. A recent phase II trial of a high-dose methotrexate regime on 63 Norwegian patients has, however, achieved a response rate of 37%. Some responses have also been achieved using interferon (IFN)-gamma administered intrapleurally or recombinant (r) IFN-alpha administered subcutaneously. Our earlier in vitro sensitivity studies of mesothelioma cell lines showed that IFN augments the response to chemotherapeutic agents in mesothelioma. The aim of this study was to assess the response of four mesothelioma cell lines, derived from diffuse asbestos-related pleural malignant mesothelioma, to methotrexate alone and in combination with recombinant IFN-alpha and IFN-gamma. Anti-proliferative effects were assayed by vital dye exclusion. A combination of IFN-alpha and IFN-gamma consistently augmented the response of the cell lines to methotrexate, by as much as 75% for one cell line, although the response to the individual IFNs was variable. We were also able to compare the effects of natural IFN-beta with those of IFN-alpha and IFN-gamma. The IFN-beta sensitivity profile for each of the four cell lines was similar to that of IFN-alpha. In two cell lines, the combination of IFN-beta and IFN-gamma produced a similar effect to the IFN-alpha and IFN-gamma combination.}, } @article {pmid7724503, year = {1995}, author = {Schneider, J and Grossgarten, K and Woitowitz, HJ}, title = {[Fatal pleural mesothelioma diseases caused by familial household contacts with asbestos fiber dust].}, journal = {Pneumologie (Stuttgart, Germany)}, volume = {49}, number = {2}, pages = {55-59}, pmid = {7724503}, issn = {0934-8387}, mesh = {Adult ; Aged ; Air Pollution, Indoor/*adverse effects ; Fatal Outcome ; Female ; Follow-Up Studies ; Humans ; Male ; Mesothelioma/*pathology ; Middle Aged ; Occupational Diseases/*pathology ; Occupational Exposure/*adverse effects ; Pleura/pathology ; Pleural Neoplasms/*pathology ; }, abstract = {The case histories of a family are described where 3 out of 4 developed asbestos-related diseases. Only the husband had direct occupational exposure handling blue-asbestos materials while working in a producing insulating factory in 1950-59. He died of pulmonary asbestosis as an occupational disease. His wife and his son died of asbestos related mesothelioma. Detailed exposure history revealed exposure to asbestos by laundering her husband's contaminated working clothes. His son was exposed to asbestos during childhood by helping his mother laundering the father's working clothes and in addition by visiting his father's working place regularly. The significance of nonoccupational exposure to asbestos is emphasized as a causative factor in the development of malignant mesothelioma.}, } @article {pmid7704388, year = {1995}, author = {Ferrer Sancho, J}, title = {[Study of pleural minerals].}, journal = {Archivos de bronconeumologia}, volume = {31}, number = {2}, pages = {49-50}, pmid = {7704388}, issn = {0300-2896}, mesh = {Asbestos/analysis ; Biopsy ; Humans ; Mesothelioma/diagnosis/pathology ; Microscopy, Electron ; Minerals/*analysis ; Pleura/*chemistry ; Pleural Effusion/etiology ; Pleural Neoplasms/diagnosis/pathology ; Pneumoconiosis/diagnosis/pathology ; Silicates/analysis ; Silicon Dioxide/analysis ; X-Ray Diffraction ; }, } @article {pmid7655961, year = {1995}, author = {Honda, Y and Delzell, E and Cole, P}, title = {An updated study of mortality among workers at a petroleum manufacturing plant.}, journal = {Journal of occupational and environmental medicine}, volume = {37}, number = {2}, pages = {194-200}, doi = {10.1097/00043764-199502000-00020}, pmid = {7655961}, issn = {1076-2752}, mesh = {Adult ; Aged ; Air Pollutants, Occupational/*adverse effects ; *Cause of Death ; Cohort Studies ; Follow-Up Studies ; Humans ; Leukemia/*chemically induced/mortality ; Male ; Middle Aged ; Occupational Diseases/*chemically induced/mortality ; Petroleum/*adverse effects ; Primary Myelofibrosis/chemically induced/mortality ; Risk Factors ; }, abstract = {This study evaluated mortality among 9796 white male workers at a petroleum-manufacturing plant. The main purpose was to examine recent patterns in leukemia mortality, for which an increase had been reported in an earlier investigation. Compared to U.S. white men, the cohort had an excess of leukemia in 1940-1979 (38 observed/23 expected; standardized mortality ratio = 168; 95% confidence interval = 119-230). In the 1980s, there was a deficit of leukemia (8 observed/14 expected; standardized mortality ratio = 55; 95% confidence interval = 24-108). However, this was balanced by an excess of myelofibrosis and myelodysplasia (4 observed, < 1 expected). These results indicate that any occupational leukemogenic exposures at the plant have been reduced to a point at which they are insufficient to cause leukemia. Hourly workers also had an excess of deaths from mesothelioma in the 1980s (8 observed, about 2.5 expected), possibly because of exposure to asbestos in the past.}, } @article {pmid7530596, year = {1995}, author = {Walker, C and Everitt, J and Ferriola, PC and Stewart, W and Mangum, J and Bermudez, E}, title = {Autocrine growth stimulation by transforming growth factor alpha in asbestos-transformed rat mesothelial cells.}, journal = {Cancer research}, volume = {55}, number = {3}, pages = {530-536}, pmid = {7530596}, issn = {0008-5472}, mesh = {Animals ; Asbestos, Crocidolite/*toxicity ; Blotting, Northern ; Cell Division/drug effects ; Cell Line ; Cell Line, Transformed ; Epidermal Growth Factor/metabolism ; ErbB Receptors/*metabolism ; Mesothelioma/chemically induced/*pathology ; Peritoneal Neoplasms/chemically induced/*pathology ; Phosphoproteins/isolation & purification/metabolism ; Phosphotyrosine ; Radioimmunoassay ; Rats ; Transforming Growth Factor alpha/*biosynthesis/*pharmacology/physiology ; Tumor Cells, Cultured ; Tyrosine/analogs & derivatives/analysis ; }, abstract = {Although the association between asbestos exposure and mesothelioma development has been established for decades, very little is known regarding the molecular mechanism(s) by which asbestos fibers induce this disease. In this series of experiments, the potential for transforming growth factor alpha (TGF-alpha) to act as an autocrine growth factor in transformed mesothelial cells was examined in rats, a model system frequently used to assess the tumorigenic potential of fibrous particulates. Both asbestos-transformed cells and spontaneously transformed cells expressed functional EGF receptors, although only the asbestos-transformed cells expressed TGF-alpha. Expression of TGF-alpha transcripts was correlated with secretion of picogram amounts of growth factor into conditioned medium by the asbestos-transformed cells. In addition, whereas TGF-alpha inhibited the growth of spontaneously transformed mesothelial cells, it stimulated the growth of asbestos-transformed cells. Neutralizing antibody that recognized TGF-alpha secreted by the asbestos-transformed cells was able to inhibit the growth of these cells. Taken together, these data indicate that TGF-alpha acts as an autocrine growth factor for asbestos-transformed rat mesothelial cells. Therefore, in asbestos-transformed mesothelial cells, altered production and responsiveness to TGF-alpha distinguish these cells from spontaneously transformed mesothelial cells. These data suggest that differences in mesothelioma etiology may be reflected in differences in the molecular alterations present in these tumors.}, } @article {pmid8868201, year = {1995}, author = {Szeszenia-Dabrowska, N and Szymczak, W and Wilczyńska, U}, title = {[Assessment of lung cancer risk due to environmental asbestos dust exposure in the general population].}, journal = {Przeglad epidemiologiczny}, volume = {49}, number = {4}, pages = {407-416}, pmid = {8868201}, issn = {0033-2100}, mesh = {Air Pollutants/*adverse effects ; Asbestos/*adverse effects ; Dust/*adverse effects ; Environmental Monitoring ; Epidemiological Monitoring ; Female ; Humans ; Lung Neoplasms/epidemiology/*etiology ; Male ; Mesothelioma/epidemiology/etiology ; Middle Aged ; *Models, Statistical ; Occupational Exposure ; Pleural Neoplasms/epidemiology/etiology ; Poland/epidemiology ; Population Surveillance ; Risk ; Survival Rate ; }, abstract = {Assessment of lung cancer risk due to environmental asbestos dust exposure in the general population was based on the model of risk extrapolation from the occupational (in asbestos-cement plant) to the environmental concentrations. 24-h determinations of asbestos fibre concentrations in the air varied considerably, from 0.4 f/l to 4.6 f/l. The lung cancer risk due to environmental exposure of the general population to asbestos dust has been estimated to be 22 cases p.a. This seems to be very low, considering that the total number of deaths from lung cancer in Poland in 1992 was about 17.5 thousand. The environmental asbestos exposures and their health effects are limited mainly to the areas located in the vicinity of asbestos plants and are attributable primarily to improper utilization of the plant wastes (for example as the surface of local roads and sports grounds at schools) and their unathorized disposal. The incidence of pleural mesothelioma among the inhabitants of those areas seems to be endemic. The endemic character of pleural mesothelioma occurrence has been recently revealed in the vicinity of one of major Polish asbestos and cement plant.}, } @article {pmid8868200, year = {1995}, author = {Szymczak, W and Szeszenia-Dabrowska, N and Wilczyńska, U}, title = {[Assessment of cancer risk in the general population of Poland due to asbestos exposure. I. Basis of methodology].}, journal = {Przeglad epidemiologiczny}, volume = {49}, number = {4}, pages = {399-406}, pmid = {8868200}, issn = {0033-2100}, mesh = {Aged ; Asbestos/*adverse effects ; Environmental Monitoring ; Environmental Pollutants/*adverse effects ; Epidemiological Monitoring ; Female ; Humans ; Male ; Mesothelioma/epidemiology/etiology ; *Models, Statistical ; Peritoneal Neoplasms/*epidemiology/etiology ; Poland/epidemiology ; Respiratory Tract Neoplasms/*epidemiology/etiology ; Risk ; }, abstract = {Two mathematical models facilitating calculation of cancer risk in people exposed to asbestos dust in the communal environment are discussed. The first helps determine a dose-response relationships when lung cancer is the exposure effect whereas the second permits calculating the probability of pleural or peritoneal mesotheliomas induction based on the level of asbestos exposure. In the case of lung cancer, the exposure is measured as a cummulated dose which equals to a product of an average concentration of asbestos fibres in 1 ml of the air multiplied by duration of exposure (in years). Thus determined relationship between asbestos exposure and the risk involved is a linear function. The effect of smoking, which undoubtedly accounts for lung cancer induction, is an element of the assessment in this model. The relationship between the risk of mesothelioma and exposure level, which is a non-linear function, is associated with the duration of exposure (in years) and the number of years since first asbestos exposure, however, it is not related to the age of person when first exposure occured or smoking habit. It may assumed that, in the case of environmental exposures, the level of exposure could be measured by the duration of exposure to a determined concentration (the exposure starts at birth to be continued throughout the whole lifetime until death). The models presented allow forecasting cancer risk based on the adopted level and duration of exposure to asbestos dust.}, } @article {pmid8866793, year = {1995}, author = {Dopp, E and Nebe, B and Hahnel, C and Papp, T and Alonso, B and Simkó, M and Schiffmann, D}, title = {Mineral fibers induce apoptosis in Syrian hamster embryo fibroblasts.}, journal = {Pathobiology : journal of immunopathology, molecular and cellular biology}, volume = {63}, number = {4}, pages = {213-221}, doi = {10.1159/000163954}, pmid = {8866793}, issn = {1015-2008}, mesh = {Animals ; Apoptosis/*drug effects ; Asbestos, Amosite/toxicity ; Asbestos, Crocidolite/toxicity ; Asbestos, Serpentine/toxicity ; Calcium Sulfate/toxicity ; Cells, Cultured ; Ceramics/toxicity ; Cricetinae ; Embryo, Mammalian/drug effects ; Fibroblasts/*drug effects ; Mesocricetus ; Mineral Fibers/*toxicity ; }, abstract = {It is known that asbestos and other mineral fibers induce lung cancer and mesothelioma. However, the primary mechanisms of fiber-induced carcinogenesis still remain to be elucidated. Previous studies, including our own, have shown that asbestos causes specific mitotic disturbances, micronucleus formation and typical changes in chromatin structure resembling those of apoptosis. This effect has been considered as programmed cell death removing damaged or pre-cancerous cells. We investigated the induction of apoptosis by asbestos (amosite, crocidolite, chrysotile) and ceramic fibers. The typical ladder pattern of DNA fragments was identified by means of gel electrophoresis, the intracellular calcium concentration was measured and flow cytometry analyses were carried out to determine the percentage of apoptotic cells. The different fibers showed different potencies for the induction of apoptosis in Syrian hamster embryo (SHE) cells. Depending on the type of fiber applied 3-33% of cells underwent apoptosis. Chrysotile proved to be the most potent inducer of apoptosis compared to the other fibers. In addition, an increase intracellular calcium level was observed in apoptotic SHE cells. Chrysotile induced apoptosis after a considerably longer exposure time (66-72 h) than cisplatin (24 h). In view of these findings we hypothesize that chrysotile induces apoptosis resulting from long-term changes in intracellular regulation pathways.}, } @article {pmid7741473, year = {1995}, author = {Berthet, B and Guieu, C and Blanc, AP and Palayodan, A and Chamlian, A and Assadourian, R}, title = {[Prolonged survival in peritoneal mesotheliomas. Apropos of a case].}, journal = {Annales de chirurgie}, volume = {49}, number = {1}, pages = {76-77}, pmid = {7741473}, issn = {0003-3944}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Combined Modality Therapy ; Fatal Outcome ; Humans ; Male ; Mesothelioma/drug therapy/*mortality/surgery ; Middle Aged ; Peritoneal Neoplasms/drug therapy/*mortality/surgery ; Time Factors ; }, abstract = {A case of peritoneal mesothelioma discovered during laparotomy for ascites is reported. A long-term survival of 5 years was observed with combined treatment: surgery and chemotherapy. Peritoneal mesothelioma is a rare neoplasm often related to asbestos exposure and its prognosis is poor. No laboratory test other than histologic examination is specific for the diagnosis. Combined treatment with radiotherapy and chemotherapy seems to improve the survival rate.}, } @article {pmid7699966, year = {1995}, author = {Tokuyama, T and Yoneda, T and Hamada, K and Yoshikawa, M and Fu, A and Tomoda, K and Nakaya, M and Narita, N and Tamura, M and Kitamura, K}, title = {[Diagnostic value of tissue polypeptide antigen in pleural effusions with malignant pleural mesothelioma].}, journal = {Nihon Kyobu Shikkan Gakkai zasshi}, volume = {33}, number = {1}, pages = {39-43}, pmid = {7699966}, issn = {0301-1542}, mesh = {Adult ; Aged ; Antigens, Neoplasm/*analysis ; Biomarkers, Tumor/*analysis ; Female ; Humans ; Male ; Mesothelioma/*diagnosis/immunology ; Middle Aged ; Peptides/*analysis ; Pleural Effusion, Malignant/*immunology ; Pleural Neoplasms/*diagnosis/immunology ; Predictive Value of Tests ; Tissue Polypeptide Antigen ; }, abstract = {There are no known tumor makers of malignant pleural mesothelioma. We measured the concentration of TPA in the pleural effusions from patients with malignant pleural mesothelioma and from patients with other pleural diseases, evaluate its clinical usefulness. The concentration of TPA was more than 7,000 U/l (mean: 18,600 +/- 9,867 U/l, n = 5) in all patients with malignant pleural mesothelioma, but it was less than 4,000 U/l in those with benign asbestos pleurisy and other benign pleural effusion (benign asbestos pleurisy 1,598 +/- 570, n = 5: p < 0.01, tuberculous pleurisy 1.37 +/- 759, n = 11: p < 0.01, others 2,497 +/- 2,152 n = 3: p < 0.05). The concentration of TPA in the pleural effusions was not significantly different between malignant pleural mesothelioma and lung cancer (12,287 +/- 17,070 U/l). However, in all patients with lung cancer and high TPA concentrations, cytologically malignant cells were detected in the pleural effusions. TPA was high in all five patients with malignant pleural mesothelioma, but cytologically malignant cells were detected in only one patient. Only in malignant pleural mesothelioma (not in other benign disease or in lung cancer) was the concentration of TPA more than 4,000 U/l, and no evidence of malignancy was obtained by cytological methods. These findings suggest that assessing TPA in the pleural effusion might contribute to the diagnosis of malignant pleural mesothelioma.}, } @article {pmid7641709, year = {1995}, author = {Both, K and Turner, DR and Henderson, DW}, title = {Loss of heterozygosity in asbestos-induced mutations in a human mesothelioma cell line.}, journal = {Environmental and molecular mutagenesis}, volume = {26}, number = {1}, pages = {67-71}, doi = {10.1002/em.2850260110}, pmid = {7641709}, issn = {0893-6692}, mesh = {Asbestos, Crocidolite/*toxicity ; Cell Line ; Cell Survival/drug effects ; *Chromosome Deletion ; Dose-Response Relationship, Drug ; HLA-A Antigens/genetics ; Humans ; Lymphocytes/*drug effects/pathology ; Mesothelioma ; *Mutagenesis ; Mutagens/*toxicity ; Tumor Cells, Cultured ; }, abstract = {The relationship between occupational or environmental exposure to asbestos and the development of mesothelioma, typically after prolonged latency, has been accepted as one of cause and effect. Most studies have concluded that asbestos is not mutagenic to mammalian cells in vitro. We have studied the potential of crocidolite asbestos to induce mutations in a stable mesothelioma cell line, using a mutation assay that measures mutation at the autosomal HLA-A locus and permits clonal growth of mutant cells. The mesothelioma cell line chosen is more akin to the in vivo target cells of asbestos than human peripheral blood lymphocytes used in previous studies. Exposure of mesothelioma cells in culture to both 200 micrograms/ml and 50 micrograms/ml crocidolite for 72 hr did not result in a statistically significant difference in the mutation frequency (MF) in the HLA-A assay when compared to the spontaneous MF in these cells. Mutations in the mesothelioma cells were classified according to their molecular basis. Notwithstanding the lack of statistically significant change in overall MF, molecular analysis of mutants obtained following exposure of mesothelioma cells to crocidolite demonstrated a statistically significant increase in the class of mutations arising from loss of heterozygosity (LOH) events involving the selection locus (HLA-A) and more distal loci. Mutations following exposure to 200 micrograms/ml and 50 micrograms/ml crocidolite showed a greater frequency of LOH than did spontaneous mutants (P < 0.01 and P < 0.001, respectively). These results correlate with those obtained in an earlier study using lymphocytes. The mesothelioma cell-based assay may be useful in detecting the mutagenicity of other asbestiform fibers and man-made fibers.}, } @article {pmid7565036, year = {1995}, author = {Melero, M and Lloveras, J and Waisman, H and Elsner, B and Baldessari, E}, title = {[Malignant peritoneal mesothelioma. An infrequent cause of prolonged fever syndrome and leucocytosis in a young adult].}, journal = {Medicina}, volume = {55}, number = {1}, pages = {48-50}, pmid = {7565036}, issn = {0025-7680}, mesh = {Adult ; Diagnosis, Differential ; Fever/*etiology ; Humans ; Leukocytosis/*etiology ; Male ; Mesothelioma/complications/*diagnosis/pathology ; Peritoneal Neoplasms/complications/*diagnosis/pathology ; }, abstract = {Peritoneal mesothelioma is a rare neoplasia usually associated with exposure to asbestos. The incidence in the population not in contact with asbestos is of one per million per year. The disease is most common in males over the age of 40, with signs and symptoms of neoplasic disease together with abdominal pain and ascitis with or without a palpable abdominal mass. We report the case of a young male without a history of exposure to asbestos who presented with prolonged fever, leukocytosis and a septated peritoneal exudate. With a presumptive diagnosis of peritoneal tuberculosis, the patient received empirical antituberculosis treatment. Because the clinical picture persisted and microbiological studies remained negative, a second exploratory laparotomy was performed which demonstrated the presence of a malignant epithelial peritoneal mesothelioma.}, } @article {pmid7553671, year = {1995}, author = {Delfino, RJ and Anton-Culver, H and Saltzstein, SL}, title = {Gender-related differences in the distribution of thoracic versus abdominal malignant mesothelioma.}, journal = {Cancer detection and prevention}, volume = {19}, number = {4}, pages = {301-307}, pmid = {7553671}, issn = {0361-090X}, mesh = {Abdominal Neoplasms/*epidemiology ; California/epidemiology ; Female ; Humans ; Incidence ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Retrospective Studies ; Sex Distribution ; Sex Factors ; Thoracic Neoplasms/*epidemiology ; }, abstract = {The relationship between malignant mesothelioma (MM) and asbestos is well established, but the determinants of host factor susceptibility of MM are not. This study probes susceptibility issues by examining gender-related differences in the distribution of 417 thoracic and 42 abdominal cases of MM from 1988-1989 California Cancer Registry databases. The age-adjusted incidence rate ratio (IRR) for male/female thoracic MM was 6.9 (95% confidence interval [CI]; 5.0-9.6) consistent with greater occupational exposure among men. However, the IRR for male/female abdominal MM was 1.5 (95% CI: 0.6-3.6). Also, average age of onset for thoracic MM was greater than for abdominal MM. Thus, some abdominal MMs may be due to nonoccupational asbestos exposure, occurring over a lifetime, interacting with host factor susceptibility. This study gives impetus to research regarding the importance of host factors and nonoccupational asbestos exposure in the etiology of malignant mesothelioma.}, } @article {pmid7501891, year = {1995}, author = {Goldberg, P and Luce, D and Billon-Galland, MA and Quénel, P and Salomon-Nekiriai, C and Nicolau, J and Brochard, P and Goldberg, M}, title = {[Potential role of environmental and domestic exposure to tremolite in pleural cancer in New Caledonia].}, journal = {Revue d'epidemiologie et de sante publique}, volume = {43}, number = {5}, pages = {444-450}, pmid = {7501891}, issn = {0398-7620}, mesh = {Air Pollutants/analysis ; Asbestos, Amphibole/*adverse effects/analysis ; Construction Materials/analysis ; Environmental Exposure/*adverse effects/analysis ; Female ; *Housing ; Humans ; Male ; Middle Aged ; New Caledonia/epidemiology ; Pleural Neoplasms/*chemically induced/epidemiology/pathology ; Population Surveillance ; Risk Factors ; }, abstract = {A previous study of respiratory cancers in New Caledonia (1978-1987) showed an excess risk of pleural cancer in this South Pacific French Territory, leading to the identification of an environmental pollution. In some villages, the residents use for their houses a whitewash made from a rock derived from local outcroppings. Analysis of samples of rock and whitewash showed that they consisted of tremolite asbestos. High levels of tremolite were detected in airborne samples collected in these villages and in biological specimens of patients with pulmonary cancer or mesothelioma; the concentrations of fibers are up to 78,000 fibers per litre of air and 44 millions of fibers per gramme of dry tissue. Besides the whitewash, the environmental exposure to tremolite fibers could also be associated with certain occupations. A case control study under process will allow the estimation of respiratory cancer risks associated with the exposure to tremolite.}, } @article {pmid7483973, year = {1995}, author = {Watteeuw, G and D'Hondt, A and Tannouri, F and Recloux, P and Hubert, C}, title = {Malignant peritoneal mesothelioma. Case report and review of the literature.}, journal = {Acta clinica Belgica}, volume = {50}, number = {4}, pages = {222-226}, doi = {10.1080/17843286.1995.11718450}, pmid = {7483973}, issn = {1784-3286}, mesh = {Asbestos/*adverse effects ; Humans ; Male ; Mesothelioma/diagnosis/*etiology/pathology ; Middle Aged ; Occupational Exposure ; Peritoneal Neoplasms/diagnosis/*etiology/pathology ; }, abstract = {We describe a peritoneal mesothelioma. There are many aspecific symptoms. Professional exposure is found in only fifty percent of cases. The histological diagnosis is often difficult. The survival period is short because of the absence of curative treatment.}, } @article {pmid7481047, year = {1995}, author = {Chailleux, E and Pioche, D and Chopra, S and Dabouis, G and Germaud, P and De Lajartre, AY and De Lajartre, M}, title = {[Epidemiology of malignant pleural mesothelioma in the Nantes-Saint Nazaire region. Course in 1956-1992].}, journal = {Revue des maladies respiratoires}, volume = {12}, number = {4}, pages = {353-357}, pmid = {7481047}, issn = {0761-8425}, mesh = {Age Factors ; Aged ; Asbestos/*adverse effects ; Cohort Studies ; Female ; France/epidemiology ; Humans ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; *Occupational Exposure ; Pleural Neoplasms/*epidemiology ; Retrospective Studies ; Sex Factors ; }, abstract = {The aim of this study was to estimate the evolution of the incidence of mesothelioma in the Loire-Atlantique department since 1956 and to register all the cases diagnosed between 1985 and 1992 and to complete the data of earlier studies carried out between 1956 and 1984. The cases were indexed from the files of the pathology department and also from demographic and occupational data concerning the patients which had been gathered retrospectively from an inquiry of patients attached either to private physicians or to a hospital service. From 1956 to 1984 there were 125 cases (119 men, 6 women) who had been diagnosed; 92 cases were registered between 1985 and 1992 (79 men and 13 women). An increase in the annual number of cases was significant. The incidence during the period 1985-1992 was 10.9 per million inhabitants (men 19.4, women 3) against 8.7 (men 17.2, women 0.8) for the period 1975 to 1984 and 2.6 (men 5.2, women 0.2) for the period 1956-1974. The mean age of the subjects at the time of diagnosis rose during the period studied (59.2 +/- 9.4 between 1956-1974 to 63.1 +/- 11.9 between 1975-1984 and 67.0 +/- 9.7 between 1985-1992). Occupational exposure to asbestos was certain or probable in 85 per cent of cases with a median duration of exposure of 25 years (range 2 months to 48 years) with a median interval between the first exposure to diagnosis of 44 years (range 10-70 years). The industrial sector most often implicated was naval construction (127 cases).(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid7997031, year = {1994}, author = {Luce, D and Brochard, P and Quénel, P and Salomon-Nekiriai, C and Goldberg, P and Billon-Galland, MA and Goldberg, M}, title = {Malignant pleural mesothelioma associated with exposure to tremolite.}, journal = {Lancet (London, England)}, volume = {344}, number = {8939-8940}, pages = {1777}, doi = {10.1016/s0140-6736(94)92919-x}, pmid = {7997031}, issn = {0140-6736}, mesh = {Adult ; Asbestos, Amphibole/*adverse effects ; Environmental Exposure ; Female ; Humans ; Male ; Mesothelioma/*etiology ; Middle Aged ; Paint/adverse effects ; Pleural Neoplasms/*etiology ; }, } @article {pmid8001022, year = {1994}, author = {Bielefeldt-Ohmann, H and Fitzpatrick, DR and Marzo, AL and Jarnicki, AG and Himbeck, RP and Davis, MR and Manning, LS and Robinson, BW}, title = {Patho- and immunobiology of malignant mesothelioma: characterisation of tumour infiltrating leucocytes and cytokine production in a murine model.}, journal = {Cancer immunology, immunotherapy : CII}, volume = {39}, number = {6}, pages = {347-359}, pmid = {8001022}, issn = {0340-7004}, mesh = {Animals ; Antigens, CD/analysis ; Cytokines/*biosynthesis ; Female ; Immunophenotyping ; Lymphocytes, Tumor-Infiltrating/*immunology ; Macrophages/pathology ; Mesothelioma/*immunology/pathology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred CBA ; Transforming Growth Factor beta/physiology ; }, abstract = {Malignant mesothelioma (MM) is an aggressive, uniformly fatal serosal tumour, usually associated with asbestos exposure, for which there currently is no effective treatment. In order to gain insight into the mechanism(s) whereby MM might escape immune surveillance, a murine model for MM was used (a) to characterise the tumour-infiltrating lymphocytes (TIL) and macrophages (TIM) phenotypically, (b) to examine systemic immune recognition of MM, and (c) to examine the possible influence of tumour-derived cytokines on systemic and local pathobiological manifestations of MM. A profound down-regulation of lymphocyte surface markers, known to be involved in T cell activation, was found in TIL. Likewise, although TIM were present in large numbers, their expression of MHC class II antigen and integrins was weak or absent, suggestive of altered functional activity. Significant amounts of cytokines, in particular transforming growth factor beta, interleukin-6 (IL-6), IL-1 and tumour necrosis factor were produced during the course of MM tumour development-directly by the MM cells and/or indirectly in response to tumour growth. These factors may contribute both to derangement of antitumour effector mechanisms and to the clinical and pathological manifestations of the disease.}, } @article {pmid7892832, year = {1994}, author = {Srebro, SH and Roggli, VL}, title = {Asbestos-related disease associated with exposure to asbestiform tremolite.}, journal = {American journal of industrial medicine}, volume = {26}, number = {6}, pages = {809-819}, doi = {10.1002/ajim.4700260610}, pmid = {7892832}, issn = {0271-3586}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Asbestos, Amphibole/*adverse effects ; Asbestosis/etiology/pathology ; Environmental Exposure/*adverse effects ; Female ; Humans ; Lung Neoplasms/*etiology/pathology ; Male ; Mesothelioma/*etiology/pathology ; Middle Aged ; Occupational Exposure/*adverse effects ; }, abstract = {Tremolite is nearly ubiquitous and represents the most common amphibole fiber in the lungs of urbanites. Tremolite asbestos is not mined or used commercially but is a frequent contaminant of chrysotile asbestos, vermiculite, and talc. Therefore, individuals exposed to these materials or to end-products containing these materials may be exposed to tremolite. We have had the opportunity to do asbestos body counts and mineral fiber analysis on pulmonary tissue from five mesothelioma cases and two asbestosis cases with pulmonary tremolite burdens greater than background levels. There were no uncoated amosite or crocidolite fibers detected in any of these cases. Three patients were occupationally exposed to chrysotile asbestos; two patients had environmental exposures (one to vermiculite and one to chrysotile and talc) and one was a household contact of a shipyard worker. The tremolite burdens for the asbestosis cases were one to two orders of magnitude greater than those for the mesothelioma cases. Our study confirms the relationship between tremolite exposure and the development of asbestos-associated diseases. Furthermore, the finding of relatively modest elevations of tremolite content in some of our mesothelioma cases suggests that, at least for some susceptible individuals, moderate exposures to tremolite-contaminated dust can produce malignant pleural mesothelioma.}, } @article {pmid7878567, year = {1994}, author = {Tondini, M and Rocco, G and Travaglini, M and Rossi, G and Buscemi, A and de Fazio, L}, title = {Pleural mesothelioma associated with non-Hodgkin's lymphoma.}, journal = {Thorax}, volume = {49}, number = {12}, pages = {1269-1270}, pmid = {7878567}, issn = {0040-6376}, mesh = {Asbestosis/*complications/pathology ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/*etiology/pathology ; Male ; Mesothelioma/*etiology/pathology ; Middle Aged ; Neoplasms, Multiple Primary/*etiology/pathology ; Pleural Neoplasms/*etiology/pathology ; }, abstract = {Occupational exposure to asbestos has been associated with an increased incidence of lung and gastric cancers, mesotheliomas, and myelolymphoid malignancies. A new observation of a patient with indirect exposure to asbestos who developed mesothelioma and plasmacytoid lymphocytic non-Hodgkin's lymphoma is described. This report and the previously described stimulation of B lymphocytes by asbestos suggests that the association of mesothelioma with lymphoid and plasma cell malignancies is not merely a coincidence.}, } @article {pmid7849863, year = {1994}, author = {Spirtas, R and Heineman, EF and Bernstein, L and Beebe, GW and Keehn, RJ and Stark, A and Harlow, BL and Benichou, J}, title = {Malignant mesothelioma: attributable risk of asbestos exposure.}, journal = {Occupational and environmental medicine}, volume = {51}, number = {12}, pages = {804-811}, pmid = {7849863}, issn = {1351-0711}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Case-Control Studies ; Cause of Death ; Female ; Humans ; Industry ; Male ; Mesothelioma/*etiology/mortality/pathology ; Middle Aged ; Occupational Diseases/etiology/mortality/pathology ; Peritoneal Neoplasms/*etiology/mortality/pathology ; Pleural Neoplasms/*etiology/mortality/pathology ; Risk Factors ; }, abstract = {OBJECTIVES: To evaluate a case-control study of malignant mesothelioma through patterns of exposure to asbestos based upon information from telephone interviews with next of kin.

METHODS: Potential cases, identified from medical files and death certificates, included all people diagnosed with malignant mesothelioma and registered during 1975-1980 by the Los Angeles County Cancer Surveillance Program, the New York State Cancer Registry (excluding New York City), and 39 large Veterans Administration hospitals. Cases whose diagnosis was confirmed in a special pathology review as definite or probable mesothelioma (n = 208) were included in the analysis. Controls (n = 533) had died of other causes, excluding cancer, respiratory disease, suicide, or violence. Direct exposure to asbestos was determined from responses to three types of questions: specific queries as to any exposure to asbestos; occupational or non-vocational participation in any of nine specific activities thought to entail exposure to asbestos; and analysis of life-time work histories. Indirect exposures were assessed through residential histories and reported contact with family members exposed to asbestos.

RESULTS: Among men with pleural mesothelioma the attributable risk (AR) for exposure to asbestos was 88% (95% confidence interval (95% CI) 76-95%). For men, the AR of peritoneal cancer was 58% (95% CI 20-89%). For women (both sites combined), the AR was 23% (95% CI 3-72%). The large differences in AR by sex are compatible with the explanations: a lower background incidence rate in women, lower exposure to asbestos, and greater misclassification among women.

CONCLUSIONS: Most of the pleural and peritoneal mesotheliomas in the men studied were attributable to exposure to asbestos. The situation in women was less definitive.}, } @article {pmid7849861, year = {1994}, author = {Lippmann, M}, title = {Deposition and retention of inhaled fibres: effects on incidence of lung cancer and mesothelioma.}, journal = {Occupational and environmental medicine}, volume = {51}, number = {12}, pages = {793-798}, pmid = {7849861}, issn = {1351-0711}, support = {ES00260/ES/NIEHS NIH HHS/United States ; ES00881/ES/NIEHS NIH HHS/United States ; }, mesh = {Asbestos/*adverse effects ; Asbestos, Amosite/adverse effects ; Asbestos, Serpentine/adverse effects ; Humans ; Incidence ; Lung Neoplasms/*epidemiology/etiology ; Mesothelioma/*epidemiology/etiology ; }, abstract = {A review of the literature on chronic inhalation studies in which rats were exposed to mineral fibres at known fibre number concentrations was undertaken to examine the specific roles of fibre length and composition on the incidences of both lung cancer and mesothelioma. For lung cancer, the percentage of lung tumours (y) could be described by a relation of the form y = a + bf + cf2, where f is the concentration of fibre numbers and a, b, and c are fitted constants. The correlation coefficients for the fitted curves were 0.76 for > 5 microns f/ml, 0.84 for > 10 microns f/ml, and 0.85 for > 20 microns f/ml. These seemed to be independent of fibre type. It has been shown that brief inhalation exposures to chrysotile fibre produces highly concentrated fibre deposits on bifurcations of alveolar ducts, and that many of these fibres are phagocytosed by the underlying type II epithelial cells within a few hours. Churg has shown that both chrysotile and amphibole fibres retained in the lungs of former miners and millers do not clear much with the years since last exposure. Thus, lung tumours may be caused by that small fraction of the inhaled fibres that are retained in the interstitium below small airway bifurcations where clearance processes are ineffective. By contrast, for mesothelioma, the (low) tumour yields seemed to be highly dependent upon fibre type. Combining the data from various studies by fibre type, the percentage of mesotheliomas was 0.6% for Zimbabwe (Rhodesian) chrysotile, 2.5% for the various amphiboles as a group, and 4.7% for Quebec (Canadian) chrysotile. This difference, together with the fact that Zimbabwe chrysotile has 2 to 3 orders of magnitude less than tremolite than Quebec chrysotile, provides support for the hypothesis that the mesotheliomas that have occurred among chrysotile miners and millers could be largely due to their exposures to tremolite fibres. The chrysotile fibres may be insufficiently biopersistent because if dissolution during translocation from their sites of deposition to sites where more durable fibres can influence the transformation or progression to mesothelioma.}, } @article {pmid7845956, year = {1994}, author = {Baur, X and Marczynski, B and Rozynek, P and Voss, B}, title = {[Bronchopulmonary precancerous conditions and tumors--risk groups from the occupational medicine viewpoint].}, journal = {Pneumologie (Stuttgart, Germany)}, volume = {48}, number = {12}, pages = {825-834}, pmid = {7845956}, issn = {0934-8387}, mesh = {Carcinoma, Bronchogenic/*etiology/pathology/prevention & control ; Humans ; Lung/pathology ; Lung Neoplasms/*etiology/pathology/prevention & control ; Occupational Diseases/*etiology/pathology/prevention & control ; Occupational Exposure/adverse effects ; Precancerous Conditions/*etiology/pathology/prevention & control ; Risk Factors ; }, abstract = {Risk groups with regard to bronchopulmonary precancerous and tumor diseases of occupational origin can be deduced from current occupational disease statistics. Most prominent are those working with asbestos. Each year about 250 asbestos-associated bronchial carcinomas and 400 mesotheliomas are recognized and compensated; the tendency is increasing. Because of the long latency time, the frequency peak will probably be reached in about 15 years in spite of the prohibition of asbestos usage. The second place is probably taken by malignomas among the underground uranium mine workers in Thuringia and Saxony (SDAG Wismut). Next come bronchial carcinomas with silicosis (carcinoma in scar tissue) after exposure to chromium(VI) and arsenic compounds as well as various other chemicals and metals. Dose-activity relationships are significant for all occupational carcinogenic agents, as there are also often syncancerogenic influences (especially smoking). From the data on previous loading, high risk groups, for example, among the insulation workers exposed to asbestos or uranium miners in the so-called "wild years", can be defined. A suitable screening method for the detection of bronchopulmonary tumors in the early stages has not yet been established. Medical checkups for the respective risk groups concentrate on the early X-ray detection of circular foci. As shown by recent studies, cytological sputum diagnosis, (fluorescence) bronchoscopy, and BAL cytology must be employed much more frequently in the high risk groups so that the prognostically more favorable stages of preneoplasm and carcinoma in situ can be detected and possibly treated curatively. These procedures are currently reaching a considerably higher sensitivity with the help of modern molecular biology techniques (e.g. detection of tumor-associated genetic changes and gene products). This contributes to an improvement in surveillance examinations with increasing detection of the curable early forms of tumors. However, only the further development of primary prevention, i.e. the greatest possible minimization or, if possible, total elimination of contact with carcinogenic agents and the consequent control of occupational protection will lead to a drastic reduction in the occupational risk of cancer.}, } @article {pmid7724853, year = {1994}, author = {McConnell, EE}, title = {Synthetic vitreous fibers--inhalation studies.}, journal = {Regulatory toxicology and pharmacology : RTP}, volume = {20}, number = {3 Pt 2}, pages = {S22-34}, pmid = {7724853}, issn = {0273-2300}, mesh = {Administration, Inhalation ; Air Pollutants, Occupational/administration & dosage/*toxicity ; Animals ; Carcinogens/toxicity ; Ceramics/*toxicity ; Cricetinae ; *Glass ; Rats ; }, abstract = {Synthetic vitreous fibers (SVFs), often referred to as "man-made vitreous fibers," are a class of materials that have their major uses for insulation against heat and sound. The original fibers are produced by melting various types of rock, clay, etc. and then blowing or extruding them into fibers of particular properties. During production and use small fractions of airborne fibers can be generated. Because of this a series of state-of-the-art inhalation studies was initiated to study the possible health hazards presented by the four major types of vitreous materials [two types of insulation glass wool, rock wool, slag wool, and four types of refractory ceramic fibers (RCF)] found in the workplace or to which the general public may be exposed. Rats and hamsters (30 mg/m3 kaolin-based RCF only) were exposed by nose-only inhalation to 3, 16, or 30 mg/m3 for 6 hr/day, 5 days/week, for 18 (hamsters) or 24 (rats) months and were held for lifetime observation (until approximately 20% survival) to study the chronic toxicity and potential carcinogenic activity of these classes of SVFs. Chrysotile or crocidolite asbestos served as positive controls. All of the fibers stimulated an inflammatory response characterized by an increase in the number of pulmonary macrophages at the level of the terminal bronchioles and proximal alveoli. RCF produced interstitial fibrosis in the walls of the proximal alveoli as early as 3 months and rock wool by 12 months. The only fiber which showed carcinogenic activity was RCF which produced a dose-related increase in both primary lung neoplasms (rats only) and mesotheliomas (rats and hamsters).}, } @article {pmid7705288, year = {1994}, author = {Moyer, VD and Cistulli, CA and Vaslet, CA and Kane, AB}, title = {Oxygen radicals and asbestos carcinogenesis.}, journal = {Environmental health perspectives}, volume = {102 Suppl 10}, number = {Suppl 10}, pages = {131-136}, pmid = {7705288}, issn = {0091-6765}, support = {R01 ES03721/ES/NIEHS NIH HHS/United States ; R01 ES05712/ES/NIEHS NIH HHS/United States ; T32 ES07272/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; *Asbestos/pharmacology ; DNA Damage ; Humans ; Mesothelioma/*etiology ; Reactive Oxygen Species/*metabolism ; }, abstract = {Asbestos fibers have been shown to generate reactive oxygen species using a variety of in vitro assays. It is hypothesized that these highly reactive metabolites mediate the development of malignant mesothelioma induced by asbestos fibers. DNA is a potential target of oxidant attack. Adaptive responses to oxidant injury have been described during exposure of mesothelial cells to asbestos fibers in vitro. Failure of these adaptive responses may lead to genetic instability and alterations in oncogenes and tumor suppressor genes that confer a proliferative advantage to emerging neoplastic mesothelial cells.}, } @article {pmid7602840, year = {1994}, author = {Kishimoto, T}, title = {[Relationship between asbestos exposure and malignant pleural mesothelioma: occurrence near the old Japanese naval shipyard].}, journal = {Nihon Kyobu Shikkan Gakkai zasshi}, volume = {32 Suppl}, number = {}, pages = {250-256}, pmid = {7602840}, issn = {0301-1542}, mesh = {Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Female ; Humans ; Japan/epidemiology ; Male ; Mesothelioma/epidemiology/*etiology ; Middle Aged ; Occupational Diseases/epidemiology/*etiology ; *Occupational Exposure ; Pleural Neoplasms/epidemiology/*etiology ; Time Factors ; }, abstract = {Kure City, Hiroshima Prefecture, was the site of a Japanese naval shipyard before World War II, and commercial ships were built there after the War. Large amounts of asbestos were used in this area primarily for shipbuilding, from before the war to around 1975. Probably due to exposure to asbestos, the incidence of malignant pleural mesothelioma is high in this city. Of the 31 patients with this disease, 27 were men. Patients over 60 years of age constituted a high percentage of the total and 28 had a history of asbestos exposure: 12 in the Japanese naval shipyard and 12 in the commercial shipyards. The average period of asbestos exposure for these 28 patients was 20 years. Malignant pleural mesothelioma developed more than 40 years after the first exposure to asbestos. Many asbestos particles and fibers were detected in the lungs and tumors of these patients. Most of the asbestos fibers detected were crocidolites or amosites. Considering that the amount of asbestos used in Japanese has been higher than in any other country, the incidence of malignant pleural mesothelioma may be expected to increase in this country. Countermeasures are now advisable.}, } @article {pmid7946382, year = {1994}, author = {Janssen, YM and Heintz, NH and Marsh, JP and Borm, PJ and Mossman, BT}, title = {Induction of c-fos and c-jun proto-oncogenes in target cells of the lung and pleura by carcinogenic fibers.}, journal = {American journal of respiratory cell and molecular biology}, volume = {11}, number = {5}, pages = {522-530}, doi = {10.1165/ajrcmb.11.5.7946382}, pmid = {7946382}, issn = {1044-1549}, support = {R01ES06499/ES/NIEHS NIH HHS/United States ; R01HL39469/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Asbestos, Crocidolite/*toxicity ; Asbestos, Serpentine/*toxicity ; Cell Division ; Ceramics/toxicity ; Cricetinae ; Epithelial Cells ; Gene Expression Regulation/drug effects ; *Genes, fos ; *Genes, jun ; Glass ; Hydrogen Peroxide/toxicity ; Ornithine Decarboxylase/metabolism ; Pleura/cytology/*drug effects ; Proto-Oncogene Mas ; RNA, Messenger/biosynthesis ; Rats ; Trachea/*drug effects ; Zeolites/toxicity ; }, abstract = {To study mechanisms of cell proliferation by asbestos and nonasbestos fibers, we examined the effects of these agents on the mRNA levels of c-fos and c-jun and ornithine decarboxylase (ODC) in hamster tracheal epithelial (HTE) cells and rat pleural mesothelial (RPM) cells, the progenitor cells of bronchogenic carcinoma and mesothelioma, respectively. In comparison with crocidolite asbestos, increases in c-jun mRNA were less striking in HTE cells after exposure to man-made vitreous fiber-10 (MMVF-10) or refractory ceramic fiber-1 (RCF-1). No c-fos mRNA was detected in HTE cells after exposure to particulates, but exposure of HTE cells to H2O2 caused striking increases in c-fos and c-jun, which preceded increases in ODC mRNA. Increases in ODC mRNA were also observed in HTE cells after exposure to nonasbestos fibers, whereas only crocidolite asbestos caused elevations in ODC mRNA in RPM cells. In RPM cells, crocidolite and chrysotile asbestos caused increases in mRNA levels of both c-fos and c-jun. No increases in proto-oncogene induction were observed using MMVF-10 or RCF-1 at nontoxic concentrations (< or = 5 micrograms/cm2 dish). Moreover, erionite, a fiber extremely potent in the causation of mesothelioma in humans, caused more dramatic elevations in c-fos and c-jun. Nonfibrous particles (riebeckite, polystyrene beads) did not alter proto-oncogene expression in these cell types, suggesting that the fibrous geometry of particulates is critical in the induction of c-fos and c-jun.}, } @article {pmid7946379, year = {1994}, author = {Gerwin, BI}, title = {Asbestos and the mesothelial cell: a molecular trail to mitogenic stimuli and suppressor gene suspects.}, journal = {American journal of respiratory cell and molecular biology}, volume = {11}, number = {5}, pages = {507-508}, doi = {10.1165/ajrcmb.11.5.7946379}, pmid = {7946379}, issn = {1044-1549}, mesh = {Animals ; Asbestos/*toxicity ; Cell Transformation, Neoplastic/*chemically induced ; *Epithelial Cells ; Epithelium/drug effects/metabolism ; Genes, Tumor Suppressor/*physiology ; Humans ; Mesothelioma/*etiology ; }, } @article {pmid7654906, year = {1994}, author = {Pérez de Oteyza, C and Torres León, JM and Menéndez Martínez, MA and Pastor Gómez, JM and García de Salazar, I and Ramírez García, JR}, title = {[Peritoneal mesothelioma: long-course ascites as the only clinical manifestation].}, journal = {Anales de medicina interna (Madrid, Spain : 1984)}, volume = {11}, number = {11}, pages = {551-552}, pmid = {7654906}, issn = {0212-7199}, mesh = {Ascites/*etiology ; Chronic Disease ; Female ; Humans ; Mesothelioma/*complications/pathology ; Middle Aged ; Peritoneal Neoplasms/*complications/pathology ; }, abstract = {The mesothelioma is a rare tumor, especially in its peritoneal location (20%). Most of these cases are related to an exposition to asbestos long time age. We present a patient with long-evolution ascites and without any other clinical manifestations. The study of the ascitic fluid, the imaging techniques and the peritoneoscopy did not allow the diagnosis in the first place. Only after one year of follow-up and when the patient recalled, in a directed interrogation, her occupational contact with asbestos thirty years age, the diagnosis could be established.}, } @article {pmid7882947, year = {1994}, author = {Gibbs, AR and Gardner, MJ and Pooley, FD and Griffiths, DM and Blight, B and Wagner, JC}, title = {Fiber levels and disease in workers from a factory predominantly using amosite.}, journal = {Environmental health perspectives}, volume = {102 Suppl 5}, number = {Suppl 5}, pages = {261-263}, pmid = {7882947}, issn = {0091-6765}, mesh = {Asbestos, Amosite/*adverse effects/metabolism ; Asbestosis/etiology ; Humans ; Lung Diseases/*etiology/metabolism ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Occupational Diseases/*etiology/metabolism ; Pulmonary Fibrosis/*etiology/metabolism ; }, abstract = {The Cape Boards Plant at Uxbridge produced insulation board containing amosite asbestos between 1947 and 1973 with only small amounts of chrysotile. After 1973 only amosite was used. In this study we examined lung samples from 48 workers who had been employed at the plant and who had come to autopsy. The study investigated the fiber levels against the lung pathology including amount of interstitial fibrosis and numbers of ferruginous bodies. The degree of interstitial fibrosis and number of asbestos bodies were graded and the tissues were analyzed by transmission electron microscopy and energy dispersive X-ray analysis and the fibers counted and typed. The 48 cases included 5 mesotheliomas and 14 lung cancers. The mineral analysis results were dominated by the amosite fiber levels. The amounts of chrysotile were relatively small. There were higher levels in lung cancer cases than mesotheliomas and higher levels in mesothelioma cases than those who had died from nonasbestos related diseases. Analysis of the lung tissues showed a consistent pattern of high amosite levels, which confirms the impression that amosite was the predominant form of asbestos used and also indicates that the factory had been a very dusty one.}, } @article {pmid7882945, year = {1994}, author = {Tossavainen, A and Karjalainen, A and Karhunen, PJ}, title = {Retention of asbestos fibers in the human body.}, journal = {Environmental health perspectives}, volume = {102 Suppl 5}, number = {Suppl 5}, pages = {253-255}, pmid = {7882945}, issn = {0091-6765}, mesh = {Adult ; Aged ; Asbestos, Amphibole/*pharmacokinetics ; Asbestos, Crocidolite/*pharmacokinetics ; Body Burden ; Humans ; Lung Neoplasms/etiology/metabolism ; Male ; Mesothelioma/etiology/metabolism ; Metabolic Clearance Rate ; Middle Aged ; Occupational Diseases/etiology/metabolism ; Occupational Exposure ; Retrospective Studies ; }, abstract = {The number, type, and size of retained asbestos fibers were measured by scanning electron microscopy (SEM) in lung tissues of 10 workers who had died from lung cancer or mesothelioma. The levels were 190-3000 x 10(6) fibers/g of dry tissue in three crocidolite sprayers, 6-39 x 10(6) fibers/g of dry tissue in two asbestos product workers and 13-280 x 10(6) fibers/g of dry tissue in five insulators exposed to anthophyllite. The duration of past exposure corresponding to the limit of 1 million fibers/g of dry tissue was 1 to 2 days in spraying, 3 to 10 days at the production plant and 1 to 4 months in insulation work. No long-term clearance of amphibole fibers, > 5 microns in length, could be demonstrated. In one of the sprayers the fiber concentrations of lung parenchyma, visceral and parietal pleura, hilar lymph nodes, and kidney cortex were orders of magnitude higher than in a series of unselected autopsies. The size and aspect ratio of crocidolite fibers in various tissues were similar, indicating that the translocation processes are rather unselective in respect to fiber dimensions.}, } @article {pmid7882942, year = {1994}, author = {Nolan, RP and Langer, AM and Addison, J}, title = {Lung content analysis of cases occupationally exposed to chrysotile asbestos.}, journal = {Environmental health perspectives}, volume = {102 Suppl 5}, number = {Suppl 5}, pages = {245-250}, pmid = {7882942}, issn = {0091-6765}, mesh = {Asbestos, Serpentine/*metabolism ; Humans ; Lung/*metabolism ; Lung Neoplasms/*metabolism ; Male ; Mesothelioma/*metabolism ; Middle Aged ; *Occupational Exposure ; Particle Size ; Reference Values ; Specimen Handling ; }, abstract = {The lung contents of six workers who had been occupationally exposed to chrysotile asbestos were examined. Five were lung cancer cases from Quebec, Canada. The sixth, an American worker who had developed pleural mesothelioma, was particularly interesting, with the lung content strikingly distinct from the Canadian cases; chrysotile, the predominant fiber in his lung, was present at a concentration 300 times that of the average total fiber content in the Canadian cases. The fiber length distribution of the chrysotile recovered from the U.S. mesothelioma case was indistinguishable from that of chrysotile specimens known to produce mesotheliomas in rats. It was also found that the characteristics of the calcium-magnesium-iron silicate fibers present in all six cases were not readily comparable to tremolite asbestos specimens known to induce mesotheliomas in animals.}, } @article {pmid7882932, year = {1994}, author = {Kogan, FM and Nikitina, OV}, title = {Solubility of chrysotile asbestos and basalt fibers in relation to their fibrogenic and carcinogenic action.}, journal = {Environmental health perspectives}, volume = {102 Suppl 5}, number = {Suppl 5}, pages = {205-206}, pmid = {7882932}, issn = {0091-6765}, mesh = {Animals ; Asbestos, Serpentine/adverse effects/*chemistry ; Carcinogens, Environmental/*adverse effects ; Fibrosis ; Minerals/adverse effects/*chemistry ; Rats ; Silicates/adverse effects/*chemistry ; Solubility ; }, abstract = {Fiber length and persistence are thought to be determinants for the development of toxic, fibrogenic, and carcinogenic effects of fibrous dusts. When the solubilities of chrysotile asbestos (CA) and basalt fibers (BF) were compared by measuring the loss of silica and magnesium in Leineweber's solution, CA was shown to be the more soluble. In a 6-month inhalation experiment, chrysotile at a mean concentration of 25 mg/m3 had a higher clearance rate than other comparable dusts. In acute toxicity studies, chrysotile and basalt fibers were administered intraperitoneally. At a dose of 1.7 g/kg body weight of CA, one third of the animals died. A dose of 2.7 g/kg body weight killed all the animals. With BF, even at a dose of 10 g/kg body weight all the animals survived. When the two fibers were administered over a 6-month period, either intratracheally or by inhalation, fibrotic lesions were more common in the group that received CA. Intraperitoneal administration of CA led to three times as many deaths from peritoneal mesothelioma as administration of BF. It appears, therefore, that in spite of its higher solubility and lower persistence, CA was the more toxic, fibrogenic and carcinogenic fiber, which gives rise to the hypothesis that the surface chemistry of the fibers is the determinant for biological activity.}, } @article {pmid7882917, year = {1994}, author = {Hesterberg, TW and Miiller, WC and Mast, R and McConnell, EE and Bernstein, DM and Anderson, R}, title = {Relationship between lung biopersistence and biological effects of man-made vitreous fibers after chronic inhalation in rats.}, journal = {Environmental health perspectives}, volume = {102 Suppl 5}, number = {Suppl 5}, pages = {133-137}, pmid = {7882917}, issn = {0091-6765}, mesh = {Administration, Inhalation ; Animals ; Asbestos, Serpentine ; Body Burden ; Ceramics ; *Glass ; Lung/*metabolism/pathology ; Male ; Rats ; Rats, Inbred F344 ; Time Factors ; World Health Organization ; }, abstract = {This article describes the relationship between fiber biopersistence and the chronic toxicity of different chemical compositions of man-made vitreous fibers (MMVF) in the lung. Rats were exposed in "nose-only" inhalation chambers, 6 hr/day, 5 days/week, for 24 months to aerosol concentrations of 30 mg/m3 containing comparable fiber numbers and similar dimensions of fibrous glass (FG) or refractory ceramic fiber (RCF). Interim sacrifices were performed periodically to monitor fiber number and dimensions in the lung and the progression of pulmonary alterations. At each interim sacrifice, three to six recovery animals were removed from each exposure group and held until two years to determine the biopersistence of fibers after different exposure times. Fibers were recovered from the ashed lungs, counted, and measured using optical and scanning electron microscopy (SEM). Fiber chemistry was assessed in 91-week recovery lungs using energy dispersive spectroscopy (EDS) analysis. RCF induced lung fibrosis and an elevation in lung tumors and pleural mesotheliomas. FG exposure resulted in no lung fibrosis, no statistically significant increase in the lung tumor incidence, and no mesotheliomas. After two years of continuous exposure, the number of World Health Organization fibers per milligram dry lung recovered from RCF and FG exposed lungs was comparable. EDS analysis of recovery lungs showed that most of the alkalis and alkaline earths had leached from the FG fibers over time. A slight change in RCF chemistry was observed. These findings indicate that the change in the chemical composition of fibers may be an important determinant of the chronic toxicity of MMVFs.}, } @article {pmid7834080, year = {1994}, author = {Watanabe, M and Kimura, N and Kato, M and Iwami, D and Takahashi, M and Nagura, H}, title = {An autopsy case of malignant mesothelioma associated with asbestosis.}, journal = {Pathology international}, volume = {44}, number = {10-11}, pages = {785-792}, doi = {10.1111/j.1440-1827.1994.tb02927.x}, pmid = {7834080}, issn = {1320-5463}, mesh = {Aged ; Asbestosis/complications/*pathology ; Humans ; Male ; Mesothelioma/etiology/*pathology ; Pleural Neoplasms/etiology/*pathology ; }, abstract = {An autopsy case of malignant mesothelioma with asbestosis caused by asbestos exposure for 17 years is reported. Autopsy revealed that mesothelioma spread extensively in all serosal tissues including pleura, pericardium, diaphragm, peritoneum and tunica vaginalis testis. Histopathologically, most of the tumor showed an epithelial form, but sarcomatous and microcystic patterns were also observed. The tumor cells had abundant glycogen and hyaluronic acid and, immunohistochemically, they were positive for cytokeratin, vimentin and epithelial membrane antigen (EMA). Long, slender microvilli were characteristically observed in these tumor cells. All of these data were compatible with malignant mesothelioma. Procollagen type I (procol.l) immunostaining was performed to reveal the mesenchymal character of mesothelioma. Both epithelial-type cells and sarcomatous-type cells showed positive staining for procol.l, although the latter showed stronger immunoreactivity. Immunostaining for procol.l was found to be one of the useful tools for distinguishing mesothelioma from adenocarcinoma. Using an extraction method for asbestos fibers, asbestos bodies were found in many tissues including lymph nodes, liver, small intestine, spleen, kidney, testis and pleura, in addition to lung parenchyma. Although multiple tumor metastases from an undetermined primary site is not ruled out, 'multifocal tumorigenesis' is suspected from the widespread deposit of asbestos fibers.}, } @article {pmid7827380, year = {1994}, author = {Seki, H and Matsumoto, K and Ohmura, K and Fukushi, Y and Fujita, T and Kiriyama, H and Takada, H and Kamii, K and Terada, H and Mori, Y}, title = {Malignant pleural mesothelioma presenting as achalasia.}, journal = {Internal medicine (Tokyo, Japan)}, volume = {33}, number = {10}, pages = {624-627}, doi = {10.2169/internalmedicine.33.624}, pmid = {7827380}, issn = {0918-2918}, mesh = {Aged ; Asbestosis/*complications ; Esophageal Achalasia/*etiology ; Humans ; Male ; Mesothelioma/*complications/diagnosis/etiology ; Pleura/pathology ; Pleural Neoplasms/*complications/diagnosis/etiology ; }, abstract = {A 65-year-old man with an occupational history of asbestos exposure developed dysphagia and vomiting. Clinical examinations at onset revealed a dilated esophagus with smooth narrowing at the gastroesophageal junction and no apparent tumor in and around the esophagus. Achalasia was suspected. Dysphagia progressed gradually and examinations performed three months after the onset disclosed a tumor in the pleural and the peritoneal cavities. At laparotomy, the tumor extended from the pleural cavity into the peritoneal cavity. Histological examination of the biopsied specimen demonstrated malignant mesothelioma. We report the first case of malignant pleural mesothelioma presenting as achalasia.}, } @article {pmid7810554, year = {1994}, author = {Infante, PF and Schuman, LD and Dement, J and Huff, J}, title = {Fibrous glass and cancer.}, journal = {American journal of industrial medicine}, volume = {26}, number = {4}, pages = {559-584}, doi = {10.1002/ajim.4700260413}, pmid = {7810554}, issn = {0271-3586}, mesh = {Administration, Inhalation ; Animals ; Case-Control Studies ; Cricetinae ; Data Interpretation, Statistical ; Female ; *Glass ; Guinea Pigs ; Humans ; Injections, Intraperitoneal ; Lung Neoplasms/epidemiology/*etiology ; Male ; Mesocricetus ; Mesothelioma/epidemiology/*etiology ; Neoplasms, Experimental ; Occupational Exposure/standards ; Papio ; Rats ; Rats, Wistar ; Research Design ; Risk Management ; }, abstract = {Some argue that fibrous glass (glass wool) should not be considered as a likely human carcinogen and hence should not be listed in the Seventh Annual Report on Carcinogens (ARC) prepared by the National Toxicology Program (NTP) and mandated by the U.S. Congress. In examining this issue, data from both laboratory experiments (animal studies) and epidemiologic studies (human data) are reviewed with the results evaluated according to the criteria established by the International Agency for Research on Cancer (IARC) and adopted in slightly modified form by the NTP for classifying substances as human carcinogens or likely human carcinogens. From our comprehensive review of the available information, we conclude that fibrous glass materials are carcinogenic, and in view of the NTP and IARC definitions should be listed in the ARC. Our review then examines the carcinogenic potency of glass fibers to humans in comparison with asbestos fibers and concludes that on a fiber-per-fiber basis, glass fibers may be as potent or even more potent than asbestos. The implications of these findings are then presented for regulatory purposes in the occupational setting.}, } @article {pmid7810543, year = {1994}, author = {Dement, JM and Brown, DP and Okun, A}, title = {Follow-up study of chrysotile asbestos textile workers: cohort mortality and case-control analyses.}, journal = {American journal of industrial medicine}, volume = {26}, number = {4}, pages = {431-447}, doi = {10.1002/ajim.4700260402}, pmid = {7810543}, issn = {0271-3586}, mesh = {Black or African American/statistics & numerical data ; Aged ; Asbestos, Serpentine/*adverse effects ; Case-Control Studies ; Cause of Death ; Female ; Follow-Up Studies ; Humans ; Logistic Models ; Lung Diseases, Obstructive/mortality ; Lung Neoplasms/ethnology/*mortality ; Male ; Mesothelioma/mortality ; Middle Aged ; Occupational Diseases/ethnology/*mortality ; Odds Ratio ; Pneumoconiosis/mortality ; Sex Distribution ; Smoking/adverse effects ; South Carolina/epidemiology ; Textile Industry/*statistics & numerical data ; Time Factors ; White People/statistics & numerical data ; }, abstract = {Previous studies of mortality among white males employed in a Charleston, South Carolina asbestos textile plant using chrysotile demonstrated significant excess mortality due to asbestos-related disease and a steep exposure-response relationship for lung cancer. This cohort was further studied by adding 15 years of follow-up and including mortality among white female and black male workers. Nested case-control analyses were undertaken to further explore possible differences in lung cancer risk by textile operation as well as possible confounding by mineral oil exposures. Preliminary data for white males have been previously published. White males experienced statistically significant excess mortality due to lung cancer (standardized mortality ratio [SMR] = 2.30; confidence interval [CI] = 1.88-2.79), all causes (SMR = 1.48; CI = 1.38-158), all cancers (SMR = 1.50; CI = 1.29-1.72), diabetes mellitus (SMR = 2.05; CI = 1.18-3.33), heart disease (SMR = 1.41; CI = 1.26-1.58), cerebrovascular disease (SMR = 1.50; CI = 1.08-2.02), pneumoconiosis and other respiratory diseases (SMR = 4.10; CI = 3.10-5.31), and accidents (SMR = 1.49; CI = 1.15-1.91). Among white females, statistically significant excesses occurred for lung cancer (SMR = 2.75; CI = 2.06-3.61), all causes (SMR = 1.21; CI = 1.11-1.32), pneumoconiosis and other respiratory diseases (SMR = 2.40; CI = 1.53-3.60), and other respiratory cancers (SMR = 14.98; CI = 4.08-38.7). Among the total cohort of black males, the only statistically significant excess observed was for pneumoconiosis (SMR = 2.19; CI = 1.23-3.62). Based on historical exposure measurements at the plant, there was a positive exposure-response relationship for both lung cancer and pneumoconiosis. Data for the entire cohort demonstrate an increase in the lung cancer relative risk of 2-3% for each fiber/cc-year of cumulative chrysotile exposure. This relationship was more consistent for the white male workers. The excess risk for lung cancer among white males and females appeared to occur at cumulative exposures lower than those for black males. Possible reasons for the lesser lung cancer risk among black males include less smoking and differences in airborne fiber characteristics experienced by black males as a result of plant job placement patterns. The case-control analysis found employment in preparation and carding operations (where most of the black males worked) to be associated with a slightly reduced lung cancer risk, although not statistically significant, whereas spinning and twisting employment was associated with a statistically significant increased lung cancer risk compared to other plant operations.(ABSTRACT TRUNCATED AT 400 WORDS)}, } @article {pmid8087335, year = {1994}, author = {Churg, A and Vedal, S}, title = {Fiber burden and patterns of asbestos-related disease in workers with heavy mixed amosite and chrysotile exposure.}, journal = {American journal of respiratory and critical care medicine}, volume = {150}, number = {3}, pages = {663-669}, doi = {10.1164/ajrccm.150.3.8087335}, pmid = {8087335}, issn = {1073-449X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos, Amosite/*adverse effects/analysis ; Asbestos, Amphibole/adverse effects/analysis ; Asbestos, Serpentine/*adverse effects/analysis ; Asbestosis/epidemiology/etiology/*pathology ; British Columbia/epidemiology ; Construction Materials/adverse effects ; Female ; Humans ; Lung/chemistry/ultrastructure ; Male ; Middle Aged ; Northwestern United States/epidemiology ; Occupational Exposure/*adverse effects/statistics & numerical data ; Regression Analysis ; Ships ; Time Factors ; }, abstract = {To attempt to determine the mineralogic factors that relate to the appearance of specific types of asbestos-related disease in workers with heavy mixed exposure to amphiboles and chrysotile, we analyzed the pulmonary asbestos fiber burden in a series of 144 shipyard workers and insulators from the Pacific Northwest. Amosite was found in all lungs, and tremolite and chrysotile in most lungs, but the vast majority of fibers were amosite. Tremolite and chrysotile concentrations were significantly correlated, indicating that the tremolite originated from chrysotile products, but no correlation was found between tremolite or chrysotile concentration and amosite concentration. Time since last exposure was correlated with decreasing amosite concentration and the calculated clearance half time was about 20 yr. In a multiple regression analysis that accounted for the presence of more than one disease in many subjects, a high concentration of amosite fibers was correlated with the presence of airway fibrosis and asbestosis, whereas subjects with mesothelioma, lung cancer, pleural plaques, or no asbestos-related disease had about the same, much lower, amosite concentration. No relationship was found between the concentration of chrysotile or tremolite and any disease. Analysis of fiber size measures (length, width, aspect ratio, surface, mass) showed that pleural plaques were strongly associated with high aspect ratio amosite fibers and suggested that mesotheliomas were associated with low aspect ratio amosite fibers.(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid7935323, year = {1994}, author = {Dorai, T and Kobayashi, H and Holland, JF and Ohnuma, T}, title = {Modulation of platelet-derived growth factor-beta mRNA expression and cell growth in a human mesothelioma cell line by a hammerhead ribozyme.}, journal = {Molecular pharmacology}, volume = {46}, number = {3}, pages = {437-444}, pmid = {7935323}, issn = {0026-895X}, mesh = {Animals ; Asbestos/adverse effects ; Base Sequence ; Cell Division/drug effects ; Cloning, Molecular ; Gene Expression/*drug effects/genetics ; Humans ; Mesothelioma/chemically induced/*genetics/metabolism/pathology ; Mice ; Mice, Nude ; Molecular Sequence Data ; Platelet-Derived Growth Factor/*genetics ; Polymerase Chain Reaction ; RNA, Catalytic/biosynthesis/genetics/*pharmacology ; RNA, Messenger/*biosynthesis ; Receptors, Platelet-Derived Growth Factor/genetics/metabolism ; Ribonucleases/chemistry ; Signal Transduction/drug effects/genetics ; Tumor Cells, Cultured ; }, abstract = {Malignant mesothelioma in humans is a rare disease, but it has recently received much public attention and concern because of its strong relationship to exposure to asbestos. We have found overexpression of the gene for platelet-derived growth factor (PDGF)-beta in several mesothelioma xenografts in nude mice. Because some mesothelioma cell lines such as VAMT-1 overexpress PDGF-beta and PDGF-beta receptors, it was considered that an autocrine loop involving PDGF-beta and its receptor may contribute to the malignant phenotype of these cells. To investigate this possibility we have developed a hammerhead ribozyme against PDGF-beta mRNA. This c-sis ribozyme was able to cleave an artificial PDGF-beta RNA substrate in a cell-free system. Transduction of this ribozyme, with the aid of a constitutive expression vector, in the VAMT-1 cell line led to a decrease in the PDGF-beta mRNA level. The ribozyme expressed in these cells was functional in cleaving the artificial RNA substrate in vitro. Ribonuclease protection assays using the ribozyme and whole PDGF-beta mRNA showed that this ribozyme was capable of cleaving the whole mRNA in vivo. Transfectant clones containing the wild-type ribozyme showed decreased cell growth, in parallel with the decreases in PDGF-beta expression. The disabled ribozyme was inactive in the cleavage reaction in vitro and in decreasing the cell growth rate in vivo. Our data indicate that in some mesothelioma cells the PDGF-beta autocrine loop may be functional and transduction of the PDGF-beta ribozyme leads to a significant reduction of cell growth. The c-sis ribozyme may be applicable in the treatment of patients with malignant mesothelioma.}, } @article {pmid7823215, year = {1994}, author = {Demers, RY and Burns, PB and Swanson, GM}, title = {Construction occupations, asbestos exposure, and cancer of the colon and rectum.}, journal = {Journal of occupational medicine. : official publication of the Industrial Medical Association}, volume = {36}, number = {9}, pages = {1027-1031}, pmid = {7823215}, issn = {0096-1736}, mesh = {Adult ; Asbestos/*adverse effects ; Cocarcinogenesis ; Colorectal Neoplasms/epidemiology/*etiology ; Construction Materials/*adverse effects ; Female ; Humans ; Male ; Mesothelioma/epidemiology/etiology ; Middle Aged ; Occupational Diseases/epidemiology/etiology ; Occupational Exposure/*adverse effects ; Odds Ratio ; Pleural Neoplasms/epidemiology/etiology ; Population Surveillance ; Risk Factors ; Smoking/adverse effects ; }, abstract = {Colorectal cancer affects more than 157,000 Americans annually. Occupational risk from exposure to asbestos dust has been implicated, leading us to explore further the possible association between colorectal cancer and asbestos. Two hundred sixty-one cases of colon and rectal cancer and 183 control cases were identified within a large, population-based case-control study conducted in southeast Michigan. Employment in occupations historically known to involve heavy exposure to asbestos was used as a surrogate for asbestos exposure. Cancers of the colon showed reduced odds ratios. Our findings differ substantially from those of the previous studies showing elevated risk. Further study is needed to address the same question, with specified asbestos exposure assessment and control for potentially significant confounders such as physical activity and diet.}, } @article {pmid7805824, year = {1994}, author = {Merler, E and Brizzi, S}, title = {Compensation of occupational diseases and particularly of asbestos-related diseases among the European Community (EEC) countries.}, journal = {Epidemiologia e prevenzione}, volume = {18}, number = {60}, pages = {170-179}, pmid = {7805824}, issn = {1120-9763}, mesh = {*Asbestosis ; Europe ; *European Union ; Humans ; Italy ; Male ; *Mesothelioma ; *Occupational Diseases ; *Pleural Neoplasms ; *Workers' Compensation ; }, abstract = {The aim of the paper is to present some of the characteristics of the compensation systems in EEC countries and to focus on the compensation of asbestos-related diseases: for each country the diseases admitted for compensation, the date of introduction into the schedule, the number of compensations awarded and a comparison between compensations for mesothelioma and mortality are presented. The data have been collected in 1990-91 by asking for information to the Compensation Institutes. The results suggest that the objective of harmonisation of the compensation systems among European countries is far from being achieved and needs re-vitalisation. The gap between knowledge and public health action has been considerable in the compensation of asbestos-related diseases, especially in the compensation of cancers. The results confirm, therefore, from a different perspective the validity of considering asbestos as a case study in public health. Finally, the Authors stress the serious situation in Italy with respect to updating the list of prescribed diseases as epidemiological data are available and to compensating occupationally related asbestos diseases.}, } @article {pmid8059765, year = {1994}, author = {Wacholder, S and Benichou, J and Heineman, EF and Hartge, P and Hoover, RN}, title = {Attributable risk: advantages of a broad definition of exposure.}, journal = {American journal of epidemiology}, volume = {140}, number = {4}, pages = {303-309}, doi = {10.1093/oxfordjournals.aje.a117252}, pmid = {8059765}, issn = {0002-9262}, mesh = {Asbestos/*adverse effects ; Bias ; Case-Control Studies ; Humans ; Likelihood Functions ; Mesothelioma/*chemically induced/classification/*epidemiology ; Occupational Exposure/*classification ; Odds Ratio ; Risk Factors ; }, abstract = {Classification of exposure into two levels--one consisting exclusively of unexposed individuals and the other consisting of exposed and perhaps unexposed ones--yields an unbiased estimate of attributable risk when misclassification is nondifferential. The authors advocate, therefore, the use of a broad definition of exposure when estimating attributable risk. Based on this idea, they justify a simple and robust method for estimating the overall attributable risk from several exposures that is based on a division of subjects into two groups, a baseline consisting of those unexposed to all exposures and everyone else.}, } @article {pmid8042566, year = {1994}, author = {Hawkins, R}, title = {Types of asbestos fibers and disease-causing potential.}, journal = {American family physician}, volume = {50}, number = {2}, pages = {308; author reply 308, 310}, pmid = {8042566}, issn = {0002-838X}, mesh = {Asbestos/*adverse effects ; Environmental Exposure ; Humans ; Mesothelioma/*etiology ; Quebec ; United States ; }, } @article {pmid8042565, year = {1994}, author = {Huncharek, M}, title = {Types of asbestos fibers and disease-causing potential.}, journal = {American family physician}, volume = {50}, number = {2}, pages = {306-8; author reply 308, 310}, pmid = {8042565}, issn = {0002-838X}, mesh = {Animals ; Asbestos, Amphibole/*adverse effects ; Environmental Exposure ; Humans ; Mesothelioma/*etiology ; Particle Size ; }, } @article {pmid8035736, year = {1994}, author = {Joseph, MR}, title = {Asbestos-related diseases.}, journal = {The Medical journal of Australia}, volume = {161}, number = {3}, pages = {228-229}, pmid = {8035736}, issn = {0025-729X}, mesh = {Asbestos/*adverse effects ; Asbestosis/epidemiology/*etiology ; Australia/epidemiology ; Female ; Humans ; Incidence ; Male ; Mesothelioma/epidemiology/*etiology ; Occupational Exposure/*adverse effects/analysis ; }, } @article {pmid7978987, year = {1994}, author = {Lippmann, M}, title = {Workshop on the health risks associated with chrysotile asbestos: a brief review.}, journal = {The Annals of occupational hygiene}, volume = {38}, number = {4}, pages = {639-642}, doi = {10.1093/annhyg/38.4.639}, pmid = {7978987}, issn = {0003-4878}, mesh = {Animals ; Asbestos, Serpentine/metabolism/*toxicity ; *Asbestosis ; Humans ; Lung/metabolism ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Mining ; *Occupational Exposure ; Pleural Neoplasms/*etiology ; Rats ; Research ; Textile Industry ; Time Factors ; }, } @article {pmid7978986, year = {1994}, author = {Woitowitz, HJ and Rödelsperger, K}, title = {Mesothelioma among car mechanics?.}, journal = {The Annals of occupational hygiene}, volume = {38}, number = {4}, pages = {635-638}, doi = {10.1093/annhyg/38.4.635}, pmid = {7978986}, issn = {0003-4878}, mesh = {Asbestos, Amphibole/analysis ; Asbestos, Serpentine/analysis ; *Automobiles ; Dust/analysis ; Humans ; Lung/chemistry ; Mesothelioma/*epidemiology ; Minerals/analysis ; *Occupations ; Pleural Neoplasms/*epidemiology ; Risk Factors ; Time Factors ; }, } @article {pmid7978985, year = {1994}, author = {Churg, A}, title = {Deposition and clearance of chrysotile asbestos.}, journal = {The Annals of occupational hygiene}, volume = {38}, number = {4}, pages = {625-33, 424-5}, doi = {10.1093/annhyg/38.4.625}, pmid = {7978985}, issn = {0003-4878}, mesh = {Animals ; Asbestos, Amosite/metabolism ; Asbestos, Amphibole/metabolism ; Asbestos, Crocidolite/metabolism ; Asbestos, Serpentine/*metabolism ; Asbestosis/metabolism ; Guinea Pigs ; Humans ; Lung/*metabolism ; Mesothelioma/metabolism ; Mining ; Occupational Exposure ; Pleura/metabolism ; Pleural Neoplasms/metabolism ; Textile Industry ; Time Factors ; }, abstract = {Studies of human lungs indicate that, for virtually all types of exposure, the relative proportion of amphibole asbestos retained in the lung far exceeds the proportion in the original dust and, conversely, the relative proportion of chrysotile is far less than that in the original dust. Although amphiboles appear to accumulate in lung in proportion to exposure and chrysotile does not, failure of chrysotile deposition is probably not the reason for the disproportionate retention of amphibole fibres. The available data suggest that chrysotile is deposited in the parenchyma but is cleared extremely rapidly, with the vast bulk of fibres removed from human lungs within weeks to months after inhalation; by comparison, amphibole clearance half-lives are of the order of years to decades. The mechanisms of preferential chrysotile clearance remain uncertain, but fragmentation of chrysotile into short fibres, possibly accompanied by extremely rapid dissolution of such fibres, appears to be important in this process. Chrysotile fibres do penetrate to the periphery of the lung, so that differences in mesothelial pathogenicity of chrysotile and amphiboles in regard to mesothelioma are not caused by failure of chrysotile to reach the pleura. The theory that the tremolite contaminant rather than the chrysotile itself is the cause of 'chrysotile-induced' disease (especially mesothelioma) is consistent with the available human data, but the contrary ideas that disease is caused either by the total transient burden of inhaled chrysotile fibres or by a small, sequestered, long-retained fraction of chrysotile fibres still need to be excluded.}, } @article {pmid7978984, year = {1994}, author = {Mossman, BT}, title = {Carcinogenesis and related cell and tissue responses to asbestos: a review.}, journal = {The Annals of occupational hygiene}, volume = {38}, number = {4}, pages = {617-24, 423}, doi = {10.1093/annhyg/38.4.617}, pmid = {7978984}, issn = {0003-4878}, mesh = {Animals ; Asbestos, Serpentine/*toxicity ; *Carcinogens ; Cell Division ; Cells, Cultured ; *Chromosome Aberrations ; Cricetinae ; Cricetulus ; Epithelial Cells ; Humans ; Lung/cytology ; Lung Neoplasms/*etiology/pathology ; Mesothelioma/*etiology/pathology ; Mice ; Pleura/cytology ; Pleural Neoplasms/*etiology/pathology ; Rats ; Smoking ; }, abstract = {A review of the literature reveals that chrysotile asbestos has a mulitiplicity of effects on cells and tissues which can provide a framework for assessment of its role(s) in initiation, promotion, or as a co-carcinogen which acts in concert with chemical carcinogens found in cigarette smoke in the development of lung cancer. Several caveats important in the interpretation of these data include the general lack of dose-response protocols both for in vivo and for in vitro studies as well as the absence, in many studies, of minerals which are appropriate positive or negative controls based on epidemiological data in man. Other factors which may account for disparities in results between studies include the use of different preparations of chrysotile fibres with distinct chemical and physical compositions and different cell types and species. Whether chrysotile is an initiator of lung cancer or mesothelioma in human cells is unclear, as evidence of chromosomal aberrations in human bronchial epithelial cells are for the most part negative (Kodoma et al., 1993; see Mossman, B., this Workshop): only one study employing pleural mesothelial cells from four individuals, two of whom exhibited chromosomal abnormalities before exposure to asbestos, has documented chromosomal changes with chrysotile, crocidolite and amosite asbestos, and this study did not use a non-pathogenic dust as a negative control. Studies using human lymphocytes show chromosomal changes after exposure to latex beads or chrysotile at equal weight concentrations (Korkina et al., 1992; see Mossman, B., this Workshop). Lastly, although both chrysotile and crocidolite asbestos demonstrated dose-dependent increase in aberrant anaphases in an SV40 T antigen-transformed human mesothelial cell line (Pelin et al., 1992, see Mossman, B., this Workshop), erionite, a potent mesotheliomagenic fibre in rodents and humans, caused no aberrations in this bioassay. Several studies have been performed to determine the interactions of chrysotile with rodent cells or isolated bacterial DNA. Results in a number of bioassays have been positive, but chrysotile is less potent on a fibre number comparative basis than crocidolite and no-observed-effect-levels (NOELs) have been observed in several systems. Cell proliferation by asbestos may be a more relevant phenomenon to tumour development and promotion, and the ability of chrysotile to stimulate cell proliferation, using a number of biomarkers, has been demonstrated both in vitro and after inhalation by rats.(ABSTRACT TRUNCATED AT 400 WORDS)}, } @article {pmid7978982, year = {1994}, author = {Pott, F}, title = {Asbestos use and carcinogenicity in Germany and a comparison with animal studies.}, journal = {The Annals of occupational hygiene}, volume = {38}, number = {4}, pages = {589-600, 420}, doi = {10.1093/annhyg/38.4.589}, pmid = {7978982}, issn = {0003-4878}, mesh = {Animals ; Asbestos/*adverse effects ; Asbestos, Amphibole/adverse effects ; Asbestos, Crocidolite/adverse effects ; Asbestos, Serpentine/adverse effects ; Case-Control Studies ; Germany, East ; Germany, West ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Multicenter Studies as Topic ; *Occupational Exposure ; Pleural Neoplasms/*etiology ; Rats ; Rats, Wistar ; Time Factors ; }, abstract = {The centralized structure of economic affairs in the former German Democratic Republic (East Germany) and the isolation from the free market led to the situation that imported asbestos was almost exclusively chrysotile. More than 90% came from the Kiembay mining area in the Ural Mountains, and about 7% was long-fibre chrysotile from Canada. Sturm and co-workers detected 1082 mesothelioma cases from 1960 to 1990 in the counties of Magdeburg and Halle. In 843 of these cases an exposure to asbestos was evident. Seventy-two cases were exposed to chrysotile only. Suspected exposure to amphiboles imported before World War II or to fibre contained in talc could not be substantiated. Up to now, there have been no analyses of lung fibre burdens from such cases. Reviewing the carcinogenicity studies in rats performed by inhalation or intra-cavitary injection of chrysotile, amosite and crocidolite fibres, the results give no clear indication of a lower carcinogenic potency per chrysotile fibre than per amphibole fibre if equal fibre numbers and fibre sizes are applied, although the chrysotile content of the lungs is relatively low. Also the mesothelioma rates after inhalation exposure to extremely high concentrations of the different asbestos fibre types are similar for chrysotile and the amphiboles and in the region of 5%. Compared with the asbestos-related cancer rates in chrysotile textile workers, rats have to be exposed to a more than 100-fold higher fibre concentration than humans to induce the same lung tumour incidence.}, } @article {pmid7978981, year = {1994}, author = {Davis, JM}, title = {Other diseases in animals.}, journal = {The Annals of occupational hygiene}, volume = {38}, number = {4}, pages = {581-7, 420}, doi = {10.1093/annhyg/38.4.581}, pmid = {7978981}, issn = {0003-4878}, mesh = {Administration, Inhalation ; Animals ; Asbestos, Amosite/administration & dosage/adverse effects ; Asbestos, Amphibole/adverse effects ; Asbestos, Serpentine/administration & dosage/*adverse effects ; Asbestosis/*veterinary ; Cricetinae ; Dust/adverse effects ; Injections ; Laryngeal Neoplasms/etiology/veterinary ; Lung Neoplasms/etiology/*veterinary ; Mesothelioma/etiology/*veterinary ; Pleural Neoplasms/etiology/*veterinary ; Pulmonary Fibrosis/etiology/veterinary ; Rats ; }, abstract = {Experimental inhalation in a number of studies has demonstrated that chrysotile asbestos can cause pulmonary fibrosis and both benign and malignant pulmonary tumours, two lesions which are associated in that the studies reporting high tumour rates also found high levels of asbestosis. One comparison reported that animals with malignant tumours had approximately twice the amount of fibrosis in the lung parenchyma as those of similar age without tumours. Many studies have examined the pathogenicity of asbestos administered by ingestion and most of these included chrysotile asbestos: the results have been universally negative apart from one study with amosite that contained no control animals and is best discarded. Only one inhalation study has reported an examination of the larynxes of animals: this found no pathological changes. In many studies, tumours other than the lung had been listed, but significant numbers of kidney tumours have never been recorded. Injection studies inducing mesothelioma have indicated that fibre geometry is important with long thin fibres (> 8 microns in length and < 0.25 microns in diameter) being the most carcinogenic. This has been difficult to confirm for inhaled fibres although fibres less than 5 microns in length appear to cause neither fibrosis nor pulmonary tumours. Similar results have been found with amosite for fibres up to 10-15 microns although longer fibres do produce these conditions. It is suggested that to produce pulmonary fibrosis and neoplasia fibres may need to be longer than 20 microns. Chrysotile has been shown in many studies to be removed from lung tissue much more rapidly than amphibole fibres.(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid7978979, year = {1994}, author = {Hillerdal, G}, title = {The human evidence: parenchymal and pleural changes.}, journal = {The Annals of occupational hygiene}, volume = {38}, number = {4}, pages = {561-7, 417}, doi = {10.1093/annhyg/38.4.561}, pmid = {7978979}, issn = {0003-4878}, mesh = {Asbestos, Serpentine/*adverse effects ; *Asbestosis/diagnostic imaging/pathology ; Humans ; Lung/diagnostic imaging/*pathology ; *Occupational Exposure ; Occupations ; Pleura/diagnostic imaging/*pathology ; Prognosis ; Radiography ; Risk Factors ; Smoking ; }, abstract = {Asbestos inhalation can cause fibrotic reactions both in the lung parenchyma and in the pleura. The incidence and relative proportions of these lesions in any cohort will be dependent on: (1) the time factor: both asbestosis and pleural plaques are progressive diseases and the longer the time from exposure, the more the changes; (2) the dose-response: the more intense the exposure, the earlier and the more advanced is the asbestosis. However, pleural plaques are only moderately dependent on the exposure level and will occur after approximately 30 years in most persons who develop them, even after fairly low exposure; (3) the early lesions are difficult to diagnose radiologically and are prone to overdiagnosis. Considerable caution is necessary when evaluating results if only such lesions are reported. It is generally accepted that the occurrence of radiological asbestosis is a risk factor, particularly for bronchial carcinoma. However, pleural plaques have been considered to be relatively harmless. Recent data have indicated, however, that they can be indicators of sufficient exposure to increase the risk of other asbestos-related diseases, including lung cancer and mesothelioma.}, } @article {pmid7978977, year = {1994}, author = {Elmes, P}, title = {Mesotheliomas and chrysotile.}, journal = {The Annals of occupational hygiene}, volume = {38}, number = {4}, pages = {547-53, 415}, doi = {10.1093/annhyg/38.4.547}, pmid = {7978977}, issn = {0003-4878}, mesh = {Animals ; Asbestos, Amphibole/adverse effects ; Asbestos, Serpentine/*adverse effects ; Humans ; Industry ; Mesothelioma/*etiology ; Mining ; Occupational Exposure ; Pleural Neoplasms/*etiology ; Risk Factors ; Rodentia ; Time Factors ; }, abstract = {Mesotheliomas are rare. While most are reported to be associated with exposure to durable fibres, a proportion are not caused by the inhalation of fibres at all. Reports of individual cases and studies of small groups are unreliable as evidence of cause because: (a) diagnosis is often unreliable; (b) even if chrysotile fibres are found in lung tissues, the mesothelioma may still be spontaneous. Present knowledge has not progressed much since 1964 when the absence of cases of mesothelioma in amosite and chrysotile miners in South Africa and the very low incidence in Canadian mines was known but not believed. Now we know this information was correct. The significance of low-level amphibole exposures in predominantly chrysotile mixes was not appreciated until studies of fibres in lungs using electron microscopy showed the high lung burden of amphibole fibres in the 1970s and 1980s. The effect of these findings is to make most European and U.S.A. factory cohorts inappropriate for the evaluation of chrysotile mesothelioma risk. Reviewing the current evidence published and unpublished, it seems likely that chrysotile uncontaminated by tremolite may not have caused any mesotheliomas even at high cumulative life-time exposures. Information on the mesothelioma risk among chrysotile user populations using fibres not containing tremolite is badly needed.}, } @article {pmid7978976, year = {1994}, author = {Berry, G}, title = {Mortality and cancer incidence of workers exposed to chrysotile asbestos in the friction-products industry.}, journal = {The Annals of occupational hygiene}, volume = {38}, number = {4}, pages = {539-46, 413}, doi = {10.1093/annhyg/38.4.539}, pmid = {7978976}, issn = {0003-4878}, mesh = {Asbestos, Serpentine/*adverse effects ; Connecticut ; Friction ; Humans ; Industry ; Lung Neoplasms/*epidemiology/mortality ; Male ; Mesothelioma/*epidemiology/mortality ; *Occupational Exposure ; Ontario ; Pleural Neoplasms/*epidemiology/mortality ; Risk Factors ; Time Factors ; United Kingdom ; }, abstract = {Three studies provide data on this topic. The largest was at the Ferodo factory in the U.K. There was no evidence of an overall excess in mortality from all causes, and in particular no increase in mortality due to lung cancer. Also, there was no evidence of any dose-response effect for lung cancer. There were 13 mesotheliomas but for 10 of these there had been exposure to crocidolite whilst working on a special contract that only a small minority of the workforce were involved in. Another one had worked in an asbestos-cement factory for 20 years. This left two mesotheliomas, one unconfirmed, for which the only known exposure was to chrysotile asbestos. The second study was of a plant in Connecticut. There was a significant increase in mortality due to respiratory cancer, but this excess was greatest in those with less than 1 year's exposure and was unrelated to cumulative exposure. No mesotheliomas occurred. The third study was of two factories in Ontario manufacturing automotive components. There was a non-significant increase in lung cancer mortality but the majority of these had not worked in the departments where asbestos was used. There were two unconfirmed mesotheliomas, one of whom had worked with friction materials. In conclusion, the three studies show that, if there are any effects on mortality due to working in the manufacture of friction materials, these effects must be small.}, } @article {pmid7978975, year = {1994}, author = {Weill, H}, title = {Biological effects: asbestos-cement manufacturing.}, journal = {The Annals of occupational hygiene}, volume = {38}, number = {4}, pages = {533-8, 413}, doi = {10.1093/annhyg/38.4.533}, pmid = {7978975}, issn = {0003-4878}, mesh = {Asbestos/*adverse effects ; *Asbestosis ; Construction Materials/*adverse effects ; Humans ; Louisiana ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; *Occupational Exposure ; Pleural Neoplasms/*etiology ; Prospective Studies ; Risk Factors ; Time Factors ; }, abstract = {Fourteen cohorts of asbestos-cement workers have been studied. These studies have demonstrated exposure-response relationships for lung cancer, mesothelioma and asbestosis. For lung cancer, relatively consistent results have been observed, with risk two-fold or less in 13 of the 14 cohorts. Among New Orleans workers, excess risk was restricted to those with X-ray evidence of asbestosis. Workers employed at least 21 years but without X-ray abnormalities, experienced no elevated risk, while those with small opacities (1/0 or higher) had substantially elevated risk (SMR > 400). Exposures in these two groups had been similar. These results suggest that asbestosis may be a necessary precursor for asbestos-induced lung cancer; if so, then the no-threshold model for lung cancer risk is inappropriate since there is general agreement that very low exposures will not result in radiologically detectable lung fibrosis. Further data on this potential link are needed. As in other industries, mesothelioma risk was strongly related to amphibole exposure, especially to crocidolite in asbestos-cement pipe manufacture. A cluster of cases has recently been reported in a family amosite-cement business. Among New Orleans workers, risk of asbestosis was related to cumulative exposure but there was little evidence of risk below 30 f ml-1-years. Progression of asbestosis in these workers was slow, related to past cumulative exposure and not related to lung function decline. Asbestosis risk is therefore not likely to develop in workers under current controlled exposure conditions.}, } @article {pmid7978974, year = {1994}, author = {Dement, JM and Brown, DP}, title = {Lung cancer mortality among asbestos textile workers: a review and update.}, journal = {The Annals of occupational hygiene}, volume = {38}, number = {4}, pages = {525-32, 412}, doi = {10.1093/annhyg/38.4.525}, pmid = {7978974}, issn = {0003-4878}, mesh = {*Asbestos, Serpentine ; *Asbestosis ; Cardiovascular Diseases/epidemiology/mortality ; Humans ; Lung Neoplasms/*epidemiology/mortality ; Male ; Mesothelioma/epidemiology/mortality ; *Occupational Exposure ; Pleural Neoplasms/epidemiology/mortality ; Risk Factors ; South Carolina/epidemiology ; *Textile Industry ; Time Factors ; }, abstract = {In an update of the mortality of the cohort of 1200 South Carolina textile workers, of whom almost half died, there were 185 excess deaths (SMR = 1.44), which included 71 cardiovascular diseases (SMR = 1.37), 43 non-malignant respiratory diseases (SMR = 2.25) and 41 lung cancers (SMR = 2.25). Only two definite mesotheliomas were observed. Other possible cases may have occurred but no confirmatory pathology was available. Strong exposure-response relationships have been found for lung cancer and for non-malignant respiratory diseases. The data suggest a doubling of the lung cancer risk at an exposure of approximately 30 fibre years. Mortality from pneumoconiosis and other respiratory diseases was elevated at even the lowest cumulative exposure category (< 2 f ml-1 years). A nested case-control analysis failed to demonstrate a significant role for mineral oil exposure in the etiology of lung cancer. Differences in airborne fibre sizes may be important in explaining different lung cancer and pneumoconiosis risks in various industries. In particular, the data on airborne fibres in textile manufacturing industries suggested 11-27% were longer than 5 microns compared to 2-5% for mining and milling.}, } @article {pmid7978973, year = {1994}, author = {Liddell, D}, title = {Cancer mortality in chrysotile mining and milling: exposure-response.}, journal = {The Annals of occupational hygiene}, volume = {38}, number = {4}, pages = {519-23, 412}, doi = {10.1093/annhyg/38.4.519}, pmid = {7978973}, issn = {0003-4878}, mesh = {Asbestos, Serpentine/*adverse effects ; *Asbestosis ; Humans ; Italy/epidemiology ; Laryngeal Neoplasms/epidemiology/etiology/mortality ; Lung Neoplasms/epidemiology/etiology/mortality ; Male ; *Mining ; Neoplasms/*epidemiology/etiology/mortality ; *Occupational Exposure ; Quebec/epidemiology ; Risk Factors ; Smoking ; Stomach Neoplasms/epidemiology/etiology/mortality ; *Textile Industry ; Time Factors ; }, abstract = {New material was presented from pending publications arising from the follow-up to 1988 of the Quebec cohort of over 10,000 chrysotile miners and millers born 1891-1920. In reviewing these and previous findings, the following conclusions were drawn; they are supported, insofar as this is possible, by the only other relevant information, that from Balangero, in Northern Italy. There is strong evidence that the risk of lung cancer as a result of exposure to chrysotile at concentrations of less than 15 million particles per cubic foot is vanishingly small. At higher concentrations, the relative risk of lung cancer is elevated, but less so in smokers of 20 or more cigarettes a day than in others. The magnitude of this risk cannot be evaluated with any certainty, but this is unimportant as these higher concentrations (above about 50 f ml-1) are well outside the range of experience nowadays. There is no evidence that the risk of laryngeal cancer or of stomach cancer are adversely affected by exposure to chrysotile. Nor is there evidence of increased risks of other abdominal malignancies or of kidney cancer among chrysotile miners and millers. The risk of mesothelioma in chrysotile miners and millers is very low compared with the risks in populations exposed to amphiboles or to mixtures of fibres including even small proportions of amphiboles.}, } @article {pmid7978972, year = {1994}, author = {Case, BW}, title = {Biological indicators of chrysotile exposure.}, journal = {The Annals of occupational hygiene}, volume = {38}, number = {4}, pages = {503-18, 410-1}, doi = {10.1093/annhyg/38.4.503}, pmid = {7978972}, issn = {0003-4878}, mesh = {Asbestos, Serpentine/adverse effects/*analysis ; *Asbestosis/pathology ; Autopsy ; Biopsy ; Bronchoalveolar Lavage Fluid ; *Environmental Exposure ; Humans ; Lung/*chemistry/pathology ; Lung Neoplasms/etiology ; Male ; Mesothelioma/etiology ; Mining ; *Occupational Exposure ; Pleural Neoplasms/etiology ; Sputum/chemistry ; }, abstract = {Chrysotile asbestos is retained in lung tissue, where it may be used as a marker of exposure. Studies include analysis of sputum and bronchoalveolar lavage fluid, but principally lung parenchyma from autopsy or surgically resected specimens. Asbestos bodies form on chrysotile fibres but are generally not a good indicator of human exposure to chrysotile because of their greater probability of formation on amphiboles. Chrysotile fibre analyses in lung have advantages and limitations. Chrysotile concentration is related to the level of environmental and occupational exposure, but in the latter situation owing to deposition, fibre alteration and clearance cumulative exposure and interval between end-exposure and death clearly affect results. Autopsy case series are biased toward increased proportions of asbestos-related diseases as compared to epidemiological cohort data. Analytical problems include potential contamination by chrysotile at autopsy, from fixatives, from post-fixative processing and in the analytical laboratory itself. These may have greatest effect in studies of individuals with low exposure, for tissue other than lung, and for short chrysotile fibres. Selection of control subjects should be contemporaneous with that of cases, and control subjects should fully reflect the hospital population at the time of case death. Limited data are available on fibre analysis in pleural tissue. More are needed. Issues requiring attention include avoidance of contamination, selection of controls, and sample site selection (parietal pleura, or tumour or plaque). For mesothelioma, two case-control studies of lung fibre burden show the principal relationship to be with long amphiboles, but some methodological problems exist. Lung cancer shows no such fibre-type differences. Asbestosis seems to be associated with long-fibre chrysotile and tremolite in one study and short fibres in others. Overall, lung retained dose is a useful indicator of chrysotile exposure if used cautiously in inference, and is very useful in the evaluation of historical exposures and industrial hygiene data in epidemiological studies.}, } @article {pmid7978969, year = {1994}, author = {Gibbs, GW}, title = {The assessment of exposure in terms of fibres.}, journal = {The Annals of occupational hygiene}, volume = {38}, number = {4}, pages = {477-87, 409-10}, doi = {10.1093/annhyg/38.4.477}, pmid = {7978969}, issn = {0003-4878}, mesh = {*Asbestos, Serpentine/adverse effects ; *Asbestosis ; Canada ; Dust ; Environmental Monitoring ; Humans ; Lung Neoplasms/etiology ; Mining ; *Occupational Exposure/analysis ; Textile Industry ; United Kingdom ; United States ; }, abstract = {The membrane filter (MF) method for evaluating asbestos fibre concentrations was introduced in the 1960s. Before that time the midget impinger (MI) was used in North America, while the long running (LRTP) and regular thermal precipitator (TP) were used in the U.K. All studies from which estimates of long-term health risks can be derived (i.e. those with individual cumulative lifetime exposure estimates) were based on the now obsolete methods. The reliability of converting these indices of exposure to MF equivalent concentrations was reviewed. It was concluded that no overall single factor could be derived for the Quebec mining and milling industry. However, it has been possible to derive conversion factors at the individual mill and work area level. Applying these in one Quebec mortality study analysis based on all jobs held by persons in the cohort gave an overall MF/MI ratio of 3.6. An examination of the confidence intervals surrounding the Quebec data, ratios derived for other chrysotile mines by other investigators, and measurements of fibre concentrations in the 1970s suggest that this was probably not unreasonable. Side-by-side and other measurements were used to convert MI concentrations in the U.S. textile industry to MF fibre concentrations. While conversions involve considerable uncertainty, independent measurements of fibres in the lung tissues of workers from the U.S. textile plant and Quebec mills show that in lungs the ratios of the concentrations of chrysotile to those of tremolite are quite consistent with the ratio of assessed exposures to these fibres in the two industries. There is an apparently higher risk of mesothelioma in one Quebec mining area (Thetford Mines) than in another (Asbestos). A high concentration of fibrous tremolite has been found in the lungs of workers in Thetford. A method of evaluating the extent to which mesothelioma risk in the chrysotile mining industry might be explained by tremolite exposures was proposed. The slope of the lung cancer dose-response relationship for the textile industry is approximately 50 times that for the mining and milling industry. Available data on the length distributions of fibres from Quebec mines and mills (up to 5% > 5 microns) and the Charleston textile plant (up to 21% > 5 microns) and some marginal indication of longer fibres in tissues from Charleston workers suggest that further work specifically addressing differences in the size distributions of long fibres in these industries is needed.}, } @article {pmid7978965, year = {1994}, author = {Langer, AM and Nolan, RP}, title = {Chrysotile: its occurrence and properties as variables controlling biological effects.}, journal = {The Annals of occupational hygiene}, volume = {38}, number = {4}, pages = {427-51, 407}, doi = {10.1093/annhyg/38.4.427}, pmid = {7978965}, issn = {0003-4878}, mesh = {Asbestos, Amphibole ; *Asbestos, Serpentine/adverse effects ; *Asbestosis ; Humans ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Pleural Neoplasms/etiology ; Research ; Surface Properties ; Trace Elements ; }, abstract = {Chrysotile formation arises through serpentinization of ultramafics and silicified dolomitic limestones. Rock types tend to control the trace metal content and both the nature and amounts of admixed minerals in the ore, such as fibrous brucite (nemalite) and tremolite. Some associated minerals and trace metals are thought to play a role in biological potential. Tremolite, one of the important associated minerals, may occur with different morphological forms, called habits. These habits range from asbestiform (tremolite asbestos) to common blocky or non-fibrous form (tremolite cleavage fragments). The latter is most common in nature. Tremolite in chrysotile ore varies in habit and concentration, both factors determining the degree of risk following inhalation. Tremolite fibre is thought to be important in relation to the occurrence of mesothelioma. Chrysotile fibrils may vary in diameter. Dust clouds generated following manipulation vary in fibre number and surface area. Chrysotile fibres exhibit a range of physical characteristics. The fibre may be non-flexible ('stiff') and low in tensile strength ('brittle'), and may lack an ability to curl. This fibre, referred to as 'harsh', sheds water more quickly than its curly, flexible 'soft' variety. The behaviour of the harsh fibres is more amphibole-like and their splintery nature suggests an enhanced inhalation potential. Slip fibre ore from Canada tends to contain more fibrous brucite (nemalite) than cross-fibre ore in the same mine. Industrial manipulation, which includes chemical treatment, heating and milling, may impart new surface properties to chrysotile dusts. Biological potential may be enhanced (opening of fibre bundles) or reduced (disruption of surface bonds and lessened ability to interact with organic moieties). Leaching of magnesium from chrysotile occurs at a pH less than about 10. Chrysotile has been demonstrated to lose magnesium in vivo and undergo clearance from the lung. The biological potential of magnesium-depleted chrysotile is much reduced, or even eliminated. Reduction of mesothelioma-inducing and cytotoxic potential has been observed and quantified experimentally. Use of chrysotile products in high-temperature environments may heat the mineral to the point where it undergoes alteration of properties, especially by dehydroxylation. Chrysotile ore may vary in properties and associated minerals: it may form aerosols with different size distributions, especially fibre/fibril diameters and surface areas; it may be associated with varying quantities of tremolite (with differing habits); it may be manipulated both industrially and environmentally to yield surfaces with different properties and, hence, differing biological potentials. Chrysotile's properties may vary from place to place and among different user industries.}, } @article {pmid7954042, year = {1994}, author = {Chen, YM and Perng, RP and Huang, MH}, title = {Pleural and pericardial mesothelioma in a general teaching hospital during the last fourteen years.}, journal = {Zhonghua yi xue za zhi = Chinese medical journal; Free China ed}, volume = {54}, number = {2}, pages = {100-104}, pmid = {7954042}, issn = {0578-1337}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Female ; Heart Neoplasms/etiology/*pathology ; Hospitals, Teaching ; Humans ; Male ; Mesothelioma/etiology/*pathology ; Middle Aged ; *Pericardium ; Pleural Neoplasms/etiology/*pathology ; Retrospective Studies ; }, abstract = {BACKGROUND: Mesothelioma is not common in Taiwan; its clinical manifestations and biological behavior in the Chinese patients have thus rarely been discussed.

METHODS: The chart records of mesothelioma patients collected from 1979 to 1992 in Veterans General Hospital-Taipei were retrospectively reviewed.

RESULTS: Sixteen thoracic mesotheliomas were diagnosed in 15 patients, including 5 benign fibrous mesotheliomas, 1 malignant pericardial mesothelioma and 10 malignant pleural mesotheliomas. One patient suffered from benign fibrous mesothelioma initially, and the disease transformed into malignant mesothelioma 5 years later. Symptoms of benign fibrous mesothelioma were nonspecific and all 5 cases occurred in lower pleural cavities. One case presented with repeated hypoglycemic coma and the initial diagnosis was hepatoma. History of asbestos exposure probably occurred in 3 of 10 malignant pleural mesotheliomas. The median survival of malignant pleural mesothelioma after onset of symptoms was 14 months. Survival seemed better in epithelial type and those who received surgical treatment of malignant mesothelioma.

CONCLUSIONS: The symptoms of mesothelioma were nonspecific. Benign fibrous mesothelioma should be considered in patients with palpable liver and hypoglycemic symptoms. Malignant transformation can occur in benign fibrous mesothelioma. Survival of malignant mesothelioma seems better in epithelial type and in those who received surgical treatment.}, } @article {pmid7953481, year = {1994}, author = {Pass, HI}, title = {Contemporary approaches in the investigation and treatment of malignant pleural mesothelioma.}, journal = {Chest surgery clinics of North America}, volume = {4}, number = {3}, pages = {497-515}, pmid = {7953481}, issn = {1052-3359}, mesh = {Asbestos/adverse effects ; Combined Modality Therapy ; Humans ; Mesothelioma/*etiology/genetics/*therapy ; Pleural Neoplasms/*etiology/genetics/*therapy ; }, abstract = {The cellular and molecular biology of mesothelioma is a complicated, multifactorial, incompletely understood process of carcinogenesis. Normal mesothelial cells can be transformed into a malignant phenotype by multiple factors, usually asbestos. Several tumor suppressor genes may be lost, and several oncogenes can be activated. A local environment of inflammation with associated release of cytokines may promote deregulated cell growth. The release of immunosuppressive substances such as nitric oxide may contribute to this process. The interaction of asbestos and viral DNA incorporation is unclear but warrants further investigation. In the majority of mesothelioma patients, present standard therapies have little effect on survival. Clinical trials studying a variety of innovative treatment strategies are being performed at centers with a significant referral base for the disease. Future treatments, however, must be based on understanding of the biology of mesothelioma.}, } @article {pmid7953476, year = {1994}, author = {Hammar, SP}, title = {The pathology of benign and malignant pleural disease.}, journal = {Chest surgery clinics of North America}, volume = {4}, number = {3}, pages = {405-430}, pmid = {7953476}, issn = {1052-3359}, mesh = {Diagnosis, Differential ; Humans ; Mesothelioma/pathology ; Pleural Diseases/microbiology/*pathology ; Pleural Effusion/pathology ; Pleural Neoplasms/*pathology/secondary ; }, abstract = {A wide spectrum of diseases involve the pleura. Many of these occur as complications of other disease processes, such as infectious pneumonitis, although a pleural effusion or a pleuritis also can be the primary manifestation of a disease. The most common primary neoplasm involving the pleura is a mesothelioma. It is of interest because of its causation by asbestos and because of its wide spectrum of histologic variability. Metastatic tumors also frequently involve the pleura but may not necessarily be biopsied. One type of metastatic neoplasm involving the pleura that may be extremely difficult to differentiate from an epithelial mesothelioma is a pseudomesotheliomatous carcinoma. In most instances, malignant neoplasms can be diagnosed accurately and distinguished from one another by ancillary techniques, such as immunohistochemistry and electron microscopy.}, } @article {pmid7807270, year = {1994}, author = {Rösler, JA and Woitowitz, HJ and Lange, HJ and Woitowitz, RH and Ulm, K and Rödelsperger, K}, title = {Mortality rates in a female cohort following asbestos exposure in Germany.}, journal = {Journal of occupational medicine. : official publication of the Industrial Medical Association}, volume = {36}, number = {8}, pages = {889-893}, pmid = {7807270}, issn = {0096-1736}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Cause of Death ; Female ; Germany/epidemiology ; Humans ; Lung Neoplasms/chemically induced/mortality ; Mesothelioma/chemically induced/mortality ; Middle Aged ; Neoplasms/*chemically induced/*mortality ; Occupational Diseases/*chemically induced/*mortality ; Occupational Exposure ; Prospective Studies ; Women's Health ; Women, Working ; }, abstract = {A cohort study was conducted of 616 German female workers with a history of exposure to asbestos. Standardized proportionate mortality analysis was done except for mesothelioma, for which proportionate mortality was computed based on best evident cause of death. Mortality from lung cancer was increased three times over expected value. Death rates due to mesothelioma were 340 times higher than in the general population. Female mortality rates surpassed those observed in men twofold for lung cancer and fourfold for mesothelioma. In comparison with published data from international cohort studies, the observed mortality for mesothelioma in our female cohort appeared higher than that previously reported. German women with a history of asbestos exposure are considered a high-risk group for developing mesothelioma and lung cancer. They should be a target group for intervention strategies (eg, chemoprevention, smoking cessation, early cancer detection).}, } @article {pmid8208519, year = {1994}, author = {Tansan, S and Emri, S and Selçuk, T and Koç, Y and Hesketh, P and Heeren, T and McCaffrey, RP and Bariş, YI}, title = {Treatment of malignant pleural mesothelioma with cisplatin, mitomycin C and alpha interferon.}, journal = {Oncology}, volume = {51}, number = {4}, pages = {348-351}, doi = {10.1159/000227363}, pmid = {8208519}, issn = {0030-2414}, mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Asbestos/adverse effects ; Cisplatin/administration & dosage ; Drug Administration Schedule ; Environmental Exposure/adverse effects ; Female ; Humans ; Interferon-alpha/administration & dosage/adverse effects ; Male ; Mesothelioma/etiology/mortality/*therapy ; Middle Aged ; Mitomycin/administration & dosage ; Pleural Neoplasms/etiology/mortality/*therapy ; Survival Rate ; Treatment Outcome ; }, abstract = {From October 1990 to September 1991, 20 consecutive patients with histologically proven malignant pleural mesothelioma (MPM), secondary to environmental exposure to asbestos or erionite, were treated with cisplatin, mitomycin C and alpha interferon (cisplatin 50 mg/m2 i.v. on day 1 of a 21-day cycle; mitomycin C 10 mg/m2 i.v. day 1 of cycles 1,3 and 5; alpha-2b-interferon 10 x 10(6) units i.m., 4 h prior to cisplatin and 10 x 10(6) units i.v. immediately prior to cisplatin day 1 of each cycle). Eighty-two treatment cycles were administered to 19 evaluable patients. Two patients attained a partial response. Eleven patients had stable disease and 6 had disease progression. Toxicities included interferon-related fever and flu-like symptoms, and vomiting. Actuarial median survival was 15 months. Three patients are alive at 20+, 21+ and 27+ months. We conclude that while the addition of alpha interferon to cisplatin and mitomycin C did not result in an objective response higher than previously reported with the cytotoxic agents alone, the trend towards an improvement in median survival as compared to a well-matched historical group suggests some benefit from the inclusion of interferon.}, } @article {pmid7947012, year = {1994}, author = {Niggli, FK and Gray, TJ and Raafat, F and Stevens, MC}, title = {Spectrum of peritoneal mesothelioma in childhood: clinical and histopathologic features, including DNA cytometry.}, journal = {Pediatric hematology and oncology}, volume = {11}, number = {4}, pages = {399-408}, doi = {10.3109/08880019409140539}, pmid = {7947012}, issn = {0888-0018}, mesh = {Adolescent ; Child, Preschool ; DNA, Neoplasm/*analysis ; Female ; Flow Cytometry ; Humans ; Infant ; Male ; Mesothelioma/chemistry/genetics/*pathology ; Peritoneal Neoplasms/chemistry/genetics/*pathology ; }, abstract = {Different types of peritoneal mesothelioma (PM) occur in children and adults. All these share certain histopathologic features but differ in other aspects, such as age of occurrence, site and sex predominance, etiology, and biologic behavior. The article describes four patients, two with cystic PM (one of whom had multiple recurrences) and two with malignant PM (one of whom had pleural metastases). These cases illustrate the variable behavior of this tumor in childhood and highlight the difficulties encountered in diagnosis and treatment. Three different groups of mesothelioma are recognized: a classic, asbestos-related, malignant mesothelioma of adults, typically occurring in the pleural cavity; a multicystic mesothelioma, predominantly affecting the pelvic peritoneum of young women and associated with a good prognosis; and mesotheliomas in children, which are not associated with asbestos exposure and have an unpredictable biologic behavior requiring individual treatment strategies. In the patients studied, DNA index measured by flow cytometry showed a difference between the cystic (aneuploid) and malignant (diploid) tumors. The proliferative rate (S phase) of the tumor was low in all four cases.}, } @article {pmid7918819, year = {1994}, author = {Sinks, T and Goodman, MT and Kolonel, LN and Anderson, B}, title = {A case-control study of mesothelioma and employment in the Hawaii sugarcane industry.}, journal = {Epidemiology (Cambridge, Mass.)}, volume = {5}, number = {4}, pages = {466-468}, doi = {10.1097/00001648-199407000-00015}, pmid = {7918819}, issn = {1044-3983}, mesh = {Agricultural Workers' Diseases/*epidemiology ; Case-Control Studies ; Hawaii/epidemiology ; Humans ; Mesothelioma/*epidemiology ; Occupational Diseases/*epidemiology ; Occupational Exposure ; Respiratory Tract Neoplasms/*epidemiology ; *Silicon Dioxide ; }, abstract = {We conducted a case-control study of 93 mesothelioma cases and 281 cancer controls to determine whether sugarcane workers exposed to biogenic silica fibers were at increased risk of mesothelioma. We found no important excess risk of mesothelioma in sugarcane workers [odds ratio (OR) = 1.3; 95% confidence interval (CI) = 0.4-3.8] when we excluded all control subjects with cancer of sites suspected of being associated with asbestos exposure. We could not identify any sugarcane workers who developed mesothelioma and worked in jobs where high exposure levels of biogenic silica fibers have been measured. We did confirm that mesothelioma risk in Hawaii is associated with probable occupational asbestos exposure. Work at the Pearl Harbor Naval Shipyard was associated with a 10-fold increase in mesothelioma when we excluded controls with cancer of sites related to asbestos exposure (OR = 10.1; 95% CI = 2.6-56.6). Work in the medical industry was also associated with an unexpected increased risk for mesothelioma (OR = 4.2; 95% CI = 1.2-15.5).}, } @article {pmid8005068, year = {1994}, author = {Barth, J and Uebelhoer, M}, title = {[Mechanisms of asbestos-induced diseases of the lungs and pleura].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {119}, number = {24}, pages = {886-891}, doi = {10.1055/s-2008-1058776}, pmid = {8005068}, issn = {0012-0472}, mesh = {Asbestosis/complications/*etiology ; Carcinoma, Bronchogenic/etiology ; Humans ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Pleural Diseases/*etiology ; Pleural Neoplasms/etiology ; }, } @article {pmid8209879, year = {1994}, author = {Homa, DM and Garabrant, DH and Gillespie, BW}, title = {A meta-analysis of colorectal cancer and asbestos exposure.}, journal = {American journal of epidemiology}, volume = {139}, number = {12}, pages = {1210-1222}, doi = {10.1093/oxfordjournals.aje.a116967}, pmid = {8209879}, issn = {0002-9262}, support = {K07-CA01291/CA/NCI NIH HHS/United States ; R25-CA57716/CA/NCI NIH HHS/United States ; T15-OH07207/OH/NIOSH CDC HHS/United States ; }, mesh = {Asbestos/*adverse effects/analysis ; Cohort Studies ; Colonic Neoplasms/chemically induced/*mortality ; Dust/analysis ; Female ; Humans ; Lung Neoplasms/mortality ; Male ; Occupational Diseases/chemically induced/*mortality ; Occupational Exposure/*adverse effects/analysis ; Poisson Distribution ; Rectal Neoplasms/chemically induced/*mortality ; Regression Analysis ; }, abstract = {A meta-analysis of the relation between asbestos exposure and colorectal cancer mortality was conducted, using published reports of 20 asbestos-exposed cohorts. Summary standardized mortality ratios (SMRs) for colorectal cancer were examined in relation to asbestos type and estimates of dust exposure (as direct estimators of asbestos exposure) and in relation to lung cancer SMR and the proportion of all deaths due to mesothelioma (as proxy estimators of asbestos exposure). An elevated summary SMR was observed in cohorts exposed to amphibole asbestos (summary SMR = 1.47; 95% confidence interval (CI) 1.09-2.00), but not in cohorts exposed to serpentine asbestos (summary SMR = 1.04; 95% CI 0.81-1.33) or in cohorts exposed to both serpentine and amphibole asbestos (summary SMR = 1.03; 95% CI 0.74-1.42). Cohorts having a lung cancer SMR greater than 2.00 had a summary SMR of 1.51 (95% CI 1.29-1.76), and cohorts in which more than 1% of all deaths were attributed to mesothelioma had a summary SMR of 1.24 (95% CI 0.94-1.64). After stratifying the cohorts based on mortality due to all cancers excluding those known or suspected to be associated with asbestos exposure, lung cancer mortality was not clearly associated with colorectal cancer mortality, suggesting that the crude association between these factors may be due to misdiagnosis of lung cancer as other types of cancer in the reported causes of death. These results suggest that exposure to amphibole asbestos may be associated with colorectal cancer, but these findings may reflect an artifact of miscertification of cause of death. The results also suggest that serpentine asbestos is not associated with colorectal cancer.}, } @article {pmid8205524, year = {1994}, author = {Walker, C and Rutten, F and Yuan, X and Pass, H and Mew, DM and Everitt, J}, title = {Wilms' tumor suppressor gene expression in rat and human mesothelioma.}, journal = {Cancer research}, volume = {54}, number = {12}, pages = {3101-3106}, pmid = {8205524}, issn = {0008-5472}, support = {NIEHS ES 06658-01/ES/NIEHS NIH HHS/United States ; }, mesh = {Aged ; Alternative Splicing ; Animals ; Asbestos/adverse effects ; Base Sequence ; Cell Transformation, Neoplastic/genetics ; Exons ; Gene Expression ; *Genes, Wilms Tumor ; Humans ; Male ; Mesothelioma/chemically induced/*genetics ; Middle Aged ; Molecular Sequence Data ; Organ Specificity ; Rats ; Testis/physiology ; }, abstract = {Induction of mesothelioma in the rat is an important animal model for assessing the carcinogenic potential of fibers and for understanding the molecular basis underlying the development of these tumors. Mesotheliomas and nephroblastoma (Wilms' tumor) have many developmental, biochemical, and histological similarities; however, the expression of the Wilms' tumor suppressor gene, WT-1, has not been well characterized in the rat, and its expression pattern in rat or human mesothelioma has not been described. We report that WT-1 transcripts (3.2 kilobases) could be detected by Northern analysis in adult rat testis, spleen, kidney, lung, heart, and glomerular mesangial cells. Normal adult mesothelial cells also expressed this gene. Rat mesothelioma cell lines expressed WT-1 transcripts of 3.2 kilobases and an additional 2.8-kilobase transcript, previously only reported to be expressed in the testis. Normal and transformed rat mesothelial cells expressed all four of the WT-1 splice variants, except testis, which only expressed WT-1 splice variants containing exon 5. Seven of seven human mesothelioma cell lines examined also expressed WT-1 transcripts, suggesting that expression of this gene may be useful in the diagnosis of these tumors.}, } @article {pmid7927012, year = {1994}, author = {Roguin, A and Ben-Shahar, M and Ben-Dror, G and Cohen, I and Hazani, E}, title = {[Malignant mesothelioma in families of asbestos workers].}, journal = {Harefuah}, volume = {126}, number = {12}, pages = {702-4, 764}, pmid = {7927012}, issn = {0017-7768}, mesh = {Adult ; Aged ; Air Pollutants, Occupational ; Asbestos/*adverse effects ; Clothing ; Environmental Exposure/*adverse effects ; *Family Health ; Female ; Humans ; Laundering ; Male ; Mesothelioma/*etiology ; Pleural Neoplasms/*etiology ; }, abstract = {Malignant mesothelioma is primarily an occupational disease of asbestos workers. While there is usually a latent period of 20-40 years between exposure and appearance of the tumor, the duration of exposure may be as short as a single month. Rarely, it may appear in family members and others living with asbestos workers who might be exposed to asbestos from work clothes during laundering, or from fibers on the skin or hair of the asbestos worker. Attention should therefore be paid to those with nonoccupational contact with asbestos. We report 2 cases of pleural mesothelioma in families of asbestos workers. In both cases the laundering of work clothes was done at home. The first was a 33-year-old man; during his childhood his father worked with asbestos boards for 5 years. The second was a 76-year-old woman whose husband worked in an asbestos factory for 32 years, up to 18 years before diagnosis.}, } @article {pmid8202946, year = {1994}, author = {Sturm, W and Menze, B and Krause, J and Thriene, B}, title = {Use of asbestos, health risks and induced occupational diseases in the former East Germany.}, journal = {Toxicology letters}, volume = {72}, number = {1-3}, pages = {317-324}, doi = {10.1016/0378-4274(94)90043-4}, pmid = {8202946}, issn = {0378-4274}, mesh = {Asbestos/*adverse effects ; Asbestos, Serpentine/adverse effects ; Bronchial Neoplasms/chemically induced/epidemiology ; Environmental Pollution/adverse effects ; Germany, East/epidemiology ; Humans ; Laryngeal Neoplasms/chemically induced/epidemiology ; Mesothelioma/chemically induced/epidemiology ; Neoplasms/*chemically induced/*epidemiology ; Occupational Diseases/*chemically induced/*epidemiology ; Risk Factors ; }, abstract = {In the period from 1960 to 1990 about 1.4 million tons of asbestos were imported and mainly processed into asbestos-cement products for the building industry. The production was concentrated in the former countries of Magdeburg and Dresden. In the past asbestos was primarily used as insulation and fire prevention material, etc. in the large-scale chemical industry. The asbestos was imported from the former Soviet Union, smaller amounts came from Canada. In the German Federal State of Saxony-Anhalt, approximately 600 asbestoses, almost 2700 pleural changes caused by asbestos, 843 asbestos-induced mesotheliomas and 787 bronchial and laryngeal carcinomas were recorded in the period from 1960 to 1990. A considerable percentage of the mesotheliomas are solely due to exposure to chrysotile asbestos.}, } @article {pmid8202944, year = {1994}, author = {Donaldson, K}, title = {Biological activity of respirable industrial fibres treated to mimic residence in the lung.}, journal = {Toxicology letters}, volume = {72}, number = {1-3}, pages = {299-305}, doi = {10.1016/0378-4274(94)90041-8}, pmid = {8202944}, issn = {0378-4274}, mesh = {Administration, Inhalation ; Animals ; Asbestos, Amosite/chemistry/*pharmacokinetics/*toxicity ; Ceramics/chemistry/*pharmacokinetics/*toxicity ; Drug Evaluation, Preclinical/methods ; Dust ; Hydrogen-Ion Concentration ; *Industry ; Lung/*metabolism ; Mice ; Mice, Inbred C57BL ; Peritoneal Cavity ; Peritonitis/*chemically induced/*metabolism ; Sensitivity and Specificity ; Solubility ; }, abstract = {The durability of fibres in the lung environment after deposition could be a key factor in determining whether they accumulate to a sufficient tissue dose to cause pathological change. There is a shortage of information on the relative durabilities of respirable industrial fibres of various types. We describe a strategy for assessing the ability of different fibre types to persist in the lung milieu and to retain their biological activity. This is particularly important for the development of mesothelioma, where the long latent time that characterises this disease would be expected to exclude, from culpability, fibres that are not durable. We have combined a pre-treatment step in pH 5.0 or 7.0 with an assay that relies on the ability of fibres to damage the mesothelium. The long-term aim is to assess the impact that treatment in various pH solutions has on (a) fibre size/number, (b) loss of key elements, (c) the ability to damage the mesothelium. Such information should enable us to better predict the potential of fibres to cause mesothelioma.}, } @article {pmid8183577, year = {1994}, author = {Carbone, M and Pass, HI and Rizzo, P and Marinetti, M and Di Muzio, M and Mew, DJ and Levine, AS and Procopio, A}, title = {Simian virus 40-like DNA sequences in human pleural mesothelioma.}, journal = {Oncogene}, volume = {9}, number = {6}, pages = {1781-1790}, pmid = {8183577}, issn = {0950-9232}, mesh = {Adult ; Aged ; Antigens, Polyomavirus Transforming/analysis ; Asbestos/adverse effects ; Base Sequence ; DNA, Viral/*analysis/chemistry ; Female ; Humans ; Male ; Mesothelioma/diagnosis/etiology/*microbiology ; Middle Aged ; Molecular Sequence Data ; Pleural Neoplasms/diagnosis/etiology/*microbiology ; Polymerase Chain Reaction ; Simian virus 40/*genetics/immunology ; Viral Proteins/analysis ; }, abstract = {Mesotheliomas are pleural, pericardial, or peritoneal neoplasms frequently associated with asbestos exposure, and it is estimated that over the next twenty years up to 80,000 new cases are expected in the USA alone. We found simian virus 40-like DNA sequences in 29 of 48 mesotheliomas studied (60%) and demonstrated simian virus large-T antigen expression in 13 of 16 specimens. The matching lung samples did not contain simian virus 40-like sequences; however, they contained asbestos. These findings are to our knowledge the first demonstration of a physical link between DNA virus-like sequences and human mesothelioma. We suggest that a simian virus 40-like virus may act independently or as a co-carcinogen with asbestos. Moreover, the selective large T antigen expression by mesothelioma and not by the surrounding pulmonary parenchyma may have both diagnostic and therapeutic implications.}, } @article {pmid8044235, year = {1994}, author = {Meurman, LO and Pukkala, E and Hakama, M}, title = {Incidence of cancer among anthophyllite asbestos miners in Finland.}, journal = {Occupational and environmental medicine}, volume = {51}, number = {6}, pages = {421-425}, pmid = {8044235}, issn = {1351-0711}, mesh = {Asbestos, Amphibole/*adverse effects ; Chi-Square Distribution ; Cohort Studies ; Female ; Finland/epidemiology ; Follow-Up Studies ; Humans ; Incidence ; Male ; *Mining ; Neoplasms/*epidemiology/etiology ; Occupational Diseases/*epidemiology/etiology ; *Occupational Exposure ; Risk Factors ; }, abstract = {A cohort of 736 male and 167 female workers of two anthophyllite mines in Finland was followed up through the Finnish Cancer Registry for cancer in 1953-91. Compared with the total cancer incidence of the east Finnish population, the men had a raised risk of total cancer (standardised incidence ratio (SIR) 1.7; 95% confidence interval (95% CI) 1.4-1.9), mainly attributable to an excess in lung cancer (SIR 2.8; 95% CI 2.2-3.6). The risk of lung cancer was somewhat higher among workers classified as heavily exposed (SIR 3.2; 95% CI 2.4-4.1) than among those moderately exposed (SIR 2.3; 95% CI 1.5-3.6) and the risk increased with increasing smoking and with increasing time of work with exposure. There were four cases of mesothelioma v 0.1 expected, all in men who smoked and had had a long and heavy asbestos exposure. Among women, a non-significant excess in total cancer (SIR 1.5; 95% CI 0.9-2.4) was found in the subgroup with heavy exposure to asbestos. Anthophyllite asbestos seems to have high potency in the carcinogenesis of lung cancer and low potency in carcinogenesis of mesothelioma in comparison with the other types of asbestos.}, } @article {pmid8013954, year = {1994}, author = {Andrion, A and Bosia, S and Paoletti, L and Feyles, E and Lanfranco, C and Bellis, D and Mollo, F}, title = {Malignant peritoneal mesothelioma in a 17-year-old boy with evidence of previous exposure to chrysotile and tremolite asbestos.}, journal = {Human pathology}, volume = {25}, number = {6}, pages = {617-622}, doi = {10.1016/0046-8177(94)90230-5}, pmid = {8013954}, issn = {0046-8177}, mesh = {Adolescent ; Asbestos, Amphibole/*adverse effects ; Asbestos, Serpentine/*adverse effects ; Autopsy ; Humans ; Male ; Mesothelioma/*etiology/pathology ; Peritoneal Neoplasms/*etiology/pathology ; }, abstract = {We describe a case of malignant peritoneal mesothelioma arising in a 17-year-old boy. The diagnosis was based on a comprehensive study including light microscopy, histochemistry, immunohistochemistry, evaluation of the clinical course, and autopsy examination. Analytical transmission electron microscopy showed a concentration of 510,000 asbestos fibers/g dry lung tissue. The fibers were represented by chrysotile (62%) and tremolite (38%) asbestos. About 40% of the total fibers were longer than 5 microns. The presence of tremolite fibers was probably due to environmental exposure to contaminated cosmetic talc. This is the first reported case of pathologically proven exposure to asbestos dust in malignant mesothelioma of childhood and adolescence.}, } @article {pmid7973494, year = {1994}, author = {Gennaro, V and Ceppi, M and Boffetta, P and Fontana, V and Perrotta, A}, title = {Pleural mesothelioma and asbestos exposure among Italian oil refinery workers.}, journal = {Scandinavian journal of work, environment & health}, volume = {20}, number = {3}, pages = {213-215}, doi = {10.5271/sjweh.1406}, pmid = {7973494}, issn = {0355-3140}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Cohort Studies ; Humans ; Italy/epidemiology ; Lung Neoplasms/etiology/*mortality ; Male ; Mesothelioma/etiology/*mortality ; Middle Aged ; Occupational Exposure/*adverse effects ; Risk Factors ; }, abstract = {OBJECTIVES: The association between asbestos exposure and risk of mesothelioma was studied among workers from two oil refineries located in the northern Italian cities of Genoa and La Spezia, given that previous cohort analyses revealed two clusters of mesotheliomas and that international cohort studies have so far not reported an excess of this neoplasm among oil refinery workers.

METHODS: Men (N = 2300) who had been employed between 1914 and 1988 in two oil refineries located in northern Italy were studied. The follow-up covered the mortality of 639 white-collar and 1661 blue-collar from 1950 to 1991.

RESULTS: Among the cases, the median duration of employment was 14.5 years, and the median time since first employment was 27.5 years. The job titles of the 10 men with pleural mesothelioma were maintenance worker (seven men), electrician (one man) and unspecified blue-collar worker (two men). Blue-collar workers experienced a significantly increased risk of pleural neoplasms, five deaths in each plant, in respect to both the provincial [standardized mortality ratio (SMR) 266] and national (SMR 1663) reference populations. The SMR, based on eight deaths, was 320 for workers with more than 10 years of employment and 20 years since first exposure.

CONCLUSIONS: The results uphold the notion that exposure to asbestos in oil refineries causes pleural mesotheliomas. This is the first study to find an excess of pleural mesotheliomas among oil refinery workers exposed to asbestos.}, } @article {pmid7925187, year = {1994}, author = {Ellouk, SA and Jaurand, MC}, title = {Review of animal/in vitro data on biological effects of man-made fibers.}, journal = {Environmental health perspectives}, volume = {102 Suppl 2}, number = {Suppl 2}, pages = {47-61}, pmid = {7925187}, issn = {0091-6765}, mesh = {Administration, Inhalation ; Animals ; Carcinogens/*toxicity ; Ceramics/toxicity ; Construction Materials/*toxicity ; Glass ; In Vitro Techniques ; Injections ; Injections, Intraperitoneal ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Pleural Neoplasms/etiology ; Trachea ; }, abstract = {This paper reviews the investigations with man-made fibers (MMF). Insulation woods: glasswool (GW), rockwool (RW), slagwool (SW), glass microfibers (GMF), glass filaments (GFiI), and refractory ceramic fibers (RCF) have been used in experimental animals and in in vitro cell systems. A large heterogeneous number of fibers, methods of fiber preparation, size selection, aerosolization, fiber size, and fiber burden measurement were noted, rendering difficult a comparison between results. By inhalation, RCF and asbestos used as positive controls produced a significant tumor increase. In some studies, a low tumor yield was found after inhalation of insulation wools; when all inhalation data were gathered, a significant tumor increase was found with GW. However, it is difficult to draw definitive conclusions on the potential of other fiber types because, in addition to the different compositions of the fibers, differences in fiber number and sizes existed, especially in comparison with asbestos. Moreover, experiments using inoculation, especially by the intraperitoneal route revealed a carcinogenic potential of all fibers types but GFiI and SW. In these two groups a small number of animals has been investigated and the fiber characteristics were sometimes irrelevant. So far, a relationship between the carcinogenic potency and fiber dimensions has been established. Other fiber parameters may be of importance (surface chemistry, biopersistence, fiber structure, for example) but further investigations are necessary to determine the correlations between these parameters and tumor incidence. In vitro experiments have emphasized the fiber characteristics identified in vivo as playing a role in the carcinogenic potency and should be developed as a better approach of the mechanistic effects of MMF.}, } @article {pmid8204662, year = {1994}, author = {Lee, MM and Green, FH and Schoel, WM and Schürch, S}, title = {Cell-substrate adhesion and metastatic potential of cultured mesothelioma cells induced by asbestos.}, journal = {Biochimica et biophysica acta}, volume = {1226}, number = {2}, pages = {151-162}, doi = {10.1016/0925-4439(94)90023-x}, pmid = {8204662}, issn = {0006-3002}, mesh = {Animals ; Asbestos/*toxicity ; Cell Adhesion/*drug effects ; Cell Division ; DNA, Neoplasm/biosynthesis ; Fibronectins ; Glass ; Laminin ; Male ; Mesothelioma/*pathology/ultrastructure ; Neoplasm Metastasis ; Rats ; Rats, Inbred F344 ; Tumor Cells, Cultured/ultrastructure ; }, abstract = {Cell-substrate adhesion was quantified for two cultured mesothelioma cell lines (epitheliomatous and sarcomatous) on glass, fibronectin and laminin substrates. Interference reflection microscopy (IRM) was used to image the adhesion patterns of cells and a grey level analysis was employed to quantify adhesion. Sarcomatous cells demonstrated marked adhesion to glass and fibronectin-coated substrates but not to laminin-coated substrate, with the greatest adhesion occurring on the fibronectin-coated surface. This adhesion was accompanied by cytoplasmic spreading. By contrast, epitheliomatous cells showed little tendency to adhere to any of the substrates and only showed significant spreading when in contact with the laminin substrate (P < 0.01). A bioassay was used to determine the metastatic potential of each of the cell lines. Via the intravenous route, the sarcomatous cells killed the host rats in 24.7 +/- 1.5 (S.D.) days compared to 27.3 +/- 0.9 (S.D.) days for the epitheliomatous cells (P < 0.01). After subcutaneous inoculation of tumour cells, the sarcomatous cells killed the host rats in 54.7 +/- 0.7 (S.D.) days compared to 48.5 +/- 0.5 (S.D.) days for the epitheliomatous cells (P < 0.01). We conclude that the results of the metastasis bioassays were consistent with the predicted behavior of these cell lines based on their ability to adhere to substrates in the in vitro adhesion assays.}, } @article {pmid8593835, year = {1994}, author = {Mossman, BT}, title = {Asbestos: facts and fiction.}, journal = {Environmental health perspectives}, volume = {102}, number = {5}, pages = {424-425}, pmid = {8593835}, issn = {0091-6765}, mesh = {Animals ; Asbestos/*adverse effects/classification ; Databases, Factual ; Environmental Health ; Humans ; Mesothelioma/etiology ; Public Opinion ; }, } @article {pmid8199683, year = {1994}, author = {Nokso-Koivisto, P and Pukkala, E}, title = {Past exposure to asbestos and combustion products and incidence of cancer among Finnish locomotive drivers.}, journal = {Occupational and environmental medicine}, volume = {51}, number = {5}, pages = {330-334}, pmid = {8199683}, issn = {1351-0711}, mesh = {Asbestos/*adverse effects ; Benzo(a)pyrene/adverse effects ; Coal/adverse effects ; Cohort Studies ; Creosote/adverse effects ; Dust/adverse effects ; Finland/epidemiology ; Humans ; Incidence ; Industry ; Male ; Neoplasms/*epidemiology/etiology ; Occupational Diseases/*epidemiology/etiology ; Occupational Exposure/*adverse effects ; Railroads ; Risk Factors ; Time Factors ; }, abstract = {Locomotive drivers in the steam engine era were exposed to asbestos during their vocational training for two years while training in workshops. Later in their career they had exposure to coal and diesel combustion products. To assess the level of earlier exposure historical working conditions were reconstructed and hygienic conditions were measured. The average exposure to asbestos (mainly anthophylline) fibres > 5 microns was 5.0 fibres/cm3. Incidence of cancer in a cohort of 8391 members of the Finnish Locomotive Drivers' Association, 1953-91, was analysed. The incidence of lung cancer and also total cancer was below the national average, probably due to the low prevalence of smoking among the drivers in the steam engine era. A four-fold risk of mesothelioma was found, most likely caused by exposure to asbestos. Also the observed 1.5-fold incidence of non-melanoma skin cancer and 1.7-fold risk of cancer of the oral cavity and pharynx may be related to occupation.}, } @article {pmid7513500, year = {1994}, author = {Nascimento, AG and Keeney, GL and Fletcher, CD}, title = {Deciduoid peritoneal mesothelioma. An unusual phenotype affecting young females.}, journal = {The American journal of surgical pathology}, volume = {18}, number = {5}, pages = {439-445}, pmid = {7513500}, issn = {0147-5185}, mesh = {Adult ; Decidua/*pathology ; Diagnosis, Differential ; Female ; Humans ; Keratins/metabolism ; Mesothelioma/genetics/metabolism/*pathology ; Microscopy, Electron ; Peritoneal Neoplasms/genetics/metabolism/*pathology ; Phenotype ; }, abstract = {Two cases of malignant peritoneal mesothelioma are reported. These tumors affected young women and displayed an unusual histopathologic pattern that closely simulated exuberant, ectopic decidual reaction or at least a malignant counterpart thereof. The importance of the differential diagnosis from decidual reaction is emphasized because decidua-like mesothelioma appears to be a highly malignant neoplasm. The cause of this lesion is unknown; and, considering the young age of the patients and the failure to demonstrate hormone receptors in the neoplastic cells, it is unlikely that asbestos exposure or hormonal imbalance played any role in the development of the disease.}, } @article {pmid8199666, year = {1994}, author = {Pairon, JC and Orlowski, E and Iwatsubo, Y and Billon-Galland, MA and Dufour, G and Chamming's, S and Archambault, C and Bignon, J and Brochard, P}, title = {Pleural mesothelioma and exposure to asbestos: evaluation from work histories and analysis of asbestos bodies in bronchoalveolar lavage fluid or lung tissue in 131 patients.}, journal = {Occupational and environmental medicine}, volume = {51}, number = {4}, pages = {244-249}, pmid = {8199666}, issn = {1351-0711}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects/analysis ; Bronchoalveolar Lavage Fluid/chemistry ; Case-Control Studies ; Dust/adverse effects ; Female ; Humans ; Industry ; Lung/chemistry ; Male ; Mesothelioma/*etiology ; Middle Aged ; Occupational Diseases/*etiology ; Occupational Exposure/*adverse effects ; Paris ; Pleural Neoplasms/*etiology ; Time Factors ; }, abstract = {Exposure to asbestos was evaluated in 131 patients with pleural malignant mesothelioma in the Paris area between 1986 and 1992 using data from a detailed specific questionnaire and light microscopy analysis of the retention of asbestos bodies in bronchoalveolar lavage fluid or lung tissue. Probable or definite exposure to significant levels of asbestos dust was identified in only 48 (36.6%) subjects, and significant asbestos body counts (above 1 asbestos body/ml in bronchoalveolar lavage fluid or 1000 asbestos bodies/g of dry lung tissue) were found in only 45 (34.3%) subjects. Overall 50 subjects had experienced exposure to only low levels of asbestos or no exposure at all and showed no significant retention of asbestos bodies in the biological sample analysed. Previous studies have shown that light microscopy may be useful in the identification of subjects with previous exposure to asbestos. In this study, apart from cases with obvious exposure to asbestos, a large group of subjects seemed to have a history of exposure or lung retention of asbestos bodies suggestive of very low levels of cumulative exposure, similar to those described in the general population.}, } @article {pmid8149491, year = {1994}, author = {Adachi, S and Yoshida, S and Kawamura, K and Takahashi, M and Uchida, H and Odagiri, Y and Takemoto, K}, title = {Inductions of oxidative DNA damage and mesothelioma by crocidolite, with special reference to the presence of iron inside and outside of asbestos fiber.}, journal = {Carcinogenesis}, volume = {15}, number = {4}, pages = {753-758}, doi = {10.1093/carcin/15.4.753}, pmid = {8149491}, issn = {0143-3334}, mesh = {Animals ; Asbestos, Crocidolite/*chemistry ; DNA/chemistry ; *DNA Damage ; Deoxyguanosine/chemistry ; Female ; Ferric Compounds/toxicity ; Iron/chemistry ; Mesothelioma/*chemically induced ; Oxidation-Reduction ; Rats ; Rats, Inbred F344 ; Reactive Oxygen Species/toxicity ; }, abstract = {Inductions of oxidative DNA damage (oh8dG) in vitro and peritoneal mesothelioma in rats (F344, female) were compared between crocidolite (CR) and de-ironized crocidolite [DCR, washed by HCl and ethylenediamine tetraacetic acid (EDTA)] to verify the hypothesis that reactive oxygen species contribute to carcinogenesis, focusing on the role of iron present inside or outside of the CR. The yield of oh8dG was 14.6 oh8dG/10(5)dG in CR and 30.2 in DCR under simple incubation with DNA. In the incubation systems added several chemicals and H2O2, DCR induced higher levels of oh8dG than CR. Especially, the addition of Fe2O3 and H2O2 to DCR increased oh8dG in DNA depending on the Fe2O3 concentration, however, this tendency was not observed in the same system of CR. Surprisingly, 7 out of 10 rats died within 2 days after the injection of 10 mg of Fe2O3 following the DCR injection (5 mg/rat), showing necroses of hepatocytes from the surface of each lobe where CR and Fe2O3 particles had been deposited together. There was no death in other groups of rats. One year after the i.p. injection of CR (5 mg/rat, single injection), mesotheliomas were found in all rats administered DCR and Fe2O3 (2 mg/rat, once a week, for 35 weeks), in 4 rats of DCR alone (n = 10), in 5 rats of CR alone (n = 10) and in none of the rats administered Fe2O3 alone (n = 10). Therefore, present results indicate that the induction of oxidative DNA damage changed even when the same type of asbestos was washed by chemical treatment, and Fe2O3 promoted the development of mesothelioma which was induced by DCR.}, } @article {pmid8137206, year = {1994}, author = {Sakai, K and Hisanaga, N and Huang, J and Shibata, E and Ono, Y and Aoki, T and Takagi, H and Ando, T and Yokoi, T and Takeuchi, Y}, title = {Asbestos and nonasbestos fiber content in lung tissue of Japanese patients with malignant mesothelioma.}, journal = {Cancer}, volume = {73}, number = {7}, pages = {1825-1835}, doi = {10.1002/1097-0142(19940401)73:7<1825::aid-cncr2820730709>3.0.co;2-m}, pmid = {8137206}, issn = {0008-543X}, mesh = {Adult ; Aged ; Aluminum Silicates/analysis ; Asbestos/*analysis/classification ; Asbestos, Amosite/analysis ; Asbestos, Amphibole/analysis ; Asbestos, Crocidolite/analysis ; Asbestos, Serpentine/analysis ; Case-Control Studies ; Electron Probe Microanalysis ; Female ; Humans ; Lung/*chemistry/pathology ; Male ; Mesothelioma/*chemistry/pathology ; Microscopy, Electron ; Middle Aged ; Occupational Exposure ; Pleural Neoplasms/*chemistry/pathology ; Silicates/analysis ; }, abstract = {BACKGROUND: Pulmonary fiber content of both asbestos and nonasbestos types were evaluated in Japanese patients with malignant pleural mesotheliomas.

METHODS: Pulmonary fiber content was analyzed in 16 patients and 16 case-matched control subjects by transmission electron microscopy with energy-dispersive X-ray analysis using a low-temperature ashing procedure.

RESULTS: The geometric mean content of total asbestos was significantly higher in the patients (22.0 x 10(6) fibers/g dry lung) than in the control subjects (2.24 x 10(6) fibers/g dry lung) (P < 0.01). When the asbestos content was analyzed by fiber type, the geometric means were also consistently and significantly higher among the patients compared with the control subjects (P < 0.01). Results were as follows: (1) amosite: patients 3.94 times 10(6) versus control subjects 0.23 x 10(6); (2) crocidolite: patients 3.56 times 10(6) versus control subjects 0.35 times 10(6); (3) total amphiboles: patients 16.0 times 10(6) versus control subjects 0.77 times 10(6); and (4) chrysotile: patients 3.76 times 10(6) versus control subjects 1.01 times 10(6). However, when individual total asbestos content was considered, 7 of the 16 patients (44%) had levels lower than the highest value noted among the control subjects. Pulmonary fiber content of patients and control subjects also revealed the presence of nonasbestos fibers. The geometric mean of nonasbestos fibers was significantly higher in the patients (87.3 x 10(6)) than in control subjects (33.8 x 10(6)) (P < 0.01). The major type of nonasbestos fibers in both groups was aluminum silicates. The mean of ratios of nonasbestos fiber contents to total asbestos contents in the patients and control subjects was 7.0 and 17.3, respectively.

CONCLUSIONS: The results were mainly in agreement with the findings of earlier investigations, but fiber content of both chrysotile and nonasbestos fiber as well as those of amphibole asbestos were significantly higher in the patients than in the control subjects.}, } @article {pmid8079137, year = {1994}, author = {Huncharek, M}, title = {Pleural mesothelioma in a cigarette filter factory worker.}, journal = {Scandinavian journal of work, environment & health}, volume = {20}, number = {2}, pages = {146-147}, doi = {10.5271/sjweh.1418}, pmid = {8079137}, issn = {0355-3140}, mesh = {Asbestos/*adverse effects ; Fatal Outcome ; Female ; Humans ; *Industry ; Mesothelioma/*chemically induced/diagnostic imaging ; Middle Aged ; Occupational Diseases/*chemically induced/diagnostic imaging ; *Occupational Exposure ; *Plants, Toxic ; Pleural Neoplasms/*chemically induced/diagnostic imaging ; Radiography ; *Nicotiana ; }, abstract = {The incidence of pleural mesothelioma is increasing. Over the past two decades many new occupational and nonoccupational risk groups have been identified. This paper reports a case of pleural mesothelioma in an office worker employed in a cigarette filter factory. Both secondary occupational and domestic asbestos exposure may have occurred. Only one prior report describes the potential asbestos health risks of this occupational group.}, } @article {pmid8034521, year = {1994}, author = {Ruckert, R and Schwarz, H}, title = {[Localized pleural mesothelioma].}, journal = {Helvetica chirurgica acta}, volume = {60}, number = {4}, pages = {475-481}, pmid = {8034521}, issn = {0018-0181}, mesh = {Aged ; Biopsy ; Diagnosis, Differential ; Female ; Humans ; Mesothelioma/mortality/pathology/*surgery ; Pleura/pathology ; Pleural Neoplasms/mortality/pathology/*surgery ; Survival Rate ; }, abstract = {About 500 cases of localized pleural mesothelioma are known from the literature. These benign or malignant tumors arise most frequently from the visceral pleura, rarely from the pericardium. They are not associated with asbestos. Correct diagnosis is rarely made preoperatively. Resection is the treatment of choice and can be curatively even in the malignant type. Clinical, radiological and pathological findings, therapy and prognosis are described.}, } @article {pmid8010303, year = {1994}, author = {Roggli, VL and Pratt, PC and Brody, AR}, title = {Fiber potency vs. importance.}, journal = {American journal of industrial medicine}, volume = {25}, number = {4}, pages = {611-612}, doi = {10.1002/ajim.4700250417}, pmid = {8010303}, issn = {0271-3586}, mesh = {Asbestos/*adverse effects/classification ; Asbestos, Amosite/adverse effects ; Asbestos, Amphibole/adverse effects ; Asbestos, Crocidolite/adverse effects ; Asbestos, Serpentine/adverse effects ; Asbestosis/complications/*etiology ; Humans ; Mesothelioma/*etiology ; Pleural Neoplasms/*etiology ; Risk Factors ; }, } @article {pmid8010302, year = {1994}, author = {Hughes, JM and Weill, H}, title = {Potency versus importance in fiber pathogenicity.}, journal = {American journal of industrial medicine}, volume = {25}, number = {4}, pages = {609-610}, doi = {10.1002/ajim.4700250416}, pmid = {8010302}, issn = {0271-3586}, mesh = {Asbestos/*adverse effects/classification ; Asbestos, Amosite/adverse effects ; Asbestos, Crocidolite/adverse effects ; Asbestos, Serpentine/adverse effects ; Asbestosis/complications/*etiology ; Humans ; Mesothelioma/*etiology ; Pleural Neoplasms/*etiology ; Risk Factors ; }, } @article {pmid7511353, year = {1994}, author = {Crotty, TB and Myers, JL and Katzenstein, AL and Tazelaar, HD and Swensen, SJ and Churg, A}, title = {Localized malignant mesothelioma. A clinicopathologic and flow cytometric study.}, journal = {The American journal of surgical pathology}, volume = {18}, number = {4}, pages = {357-363}, pmid = {7511353}, issn = {0147-5185}, mesh = {Adult ; Aged ; Aneuploidy ; Asbestos/adverse effects ; DNA, Neoplasm/analysis ; Female ; Flow Cytometry ; Humans ; Immunohistochemistry ; Keratins/analysis ; Male ; Membrane Glycoproteins/analysis ; Mesothelioma/chemistry/etiology/*pathology ; Middle Aged ; Mucin-1 ; Pleural Neoplasms/chemistry/etiology/*pathology ; }, abstract = {Six examples of malignant mesothelioma appearing as a localized pleural mass are described. There were four women and two men, ranging in age from 42 to 76 years. A history of asbestos exposure was obtained from three patients. The tumors ranged in size from 2.8 to 10 cm. Two were pedunculated and four were sessile with broad-based pleural attachments. Histologically, three tumors were purely epithelioid and three were biphasic. Immunohistochemical stains in all six cases were positive for cytokeratin and negative for carcinoembryonic antigen. Five were also positive for epithelial membrane antigen. Five were negative for Leu-M1, while one showed focal staining in a peripheral membrane pattern. Electron microscopy in two purely epithelioid tumors showed long, thin microvilli, well-developed desmosomes, and numerous tonofilaments. Flow cytometry showed an aneuploid DNA content in four tumors and a diploid content in one. Flow cytometry in five cases identified a DNA aneuploid cell population in four tumors and a diploid population in one. Three patients showed signs of local recurrences 4, 7, and 18 months after excision and died of their disease 12, 10, and 24 months after diagnosis, respectively. Three patients are well with no evidence of disease 8, 24, and 96 months after diagnosis. These findings indicate that malignant mesotheliomas of the pleura may rarely appear as a localized mass. The biologic behavior of such tumors is difficult to predict, but some patients survive disease-free for a long time after surgical excision.}, } @article {pmid8160663, year = {1994}, author = {Ribak, J}, title = {Inconsistencies and delays in asbestos evaluations.}, journal = {American journal of industrial medicine}, volume = {25}, number = {3}, pages = {455-456}, doi = {10.1002/ajim.4700250313}, pmid = {8160663}, issn = {0271-3586}, mesh = {Asbestos/adverse effects/*history ; History, 20th Century ; Humans ; Lung Neoplasms/etiology/*history ; Mesothelioma/etiology/history ; Occupational Diseases/etiology/*history ; Occupational Exposure/history ; }, } @article {pmid8130852, year = {1994}, author = {Karjalainen, A and Meurman, LO and Pukkala, E}, title = {Four cases of mesothelioma among Finnish anthophyllite miners.}, journal = {Occupational and environmental medicine}, volume = {51}, number = {3}, pages = {212-215}, pmid = {8130852}, issn = {1351-0711}, mesh = {Aged ; Asbestos, Amphibole/*adverse effects ; Finland/epidemiology ; Humans ; Male ; Mesothelioma/etiology/*mortality ; Middle Aged ; *Mining ; Occupational Diseases/etiology/*mortality ; *Occupational Exposure ; Time Factors ; }, abstract = {Four cases of mesothelioma in a cohort of 999 Finnish anthophyllite miners and millers are described. Three deaths were due to pleural mesothelioma and one to peritoneal mesothelioma among the total of 503 male deaths up to 1991. All four patients with mesothelioma had had long term (13 to 31 years) exposure in anthophyllite mining and milling. The latency time from the onset of employment until diagnosis was 39 to 58 years. All four patients were smokers or ex-smokers and had asbestosis. In three of the cases the pulmonary fibre concentration and fibre type were analysed by transmission electron microscopy. High concentrations (270 to 1100 million fibres/g dry tissue) of anthophyllite fibres were detected. The anthophyllite fibres were thicker and had lower aspect ratios than the values reported for crocidolite fibres retained in the lungs of patients with mesothelioma.}, } @article {pmid8072444, year = {1994}, author = {Magnani, C and Comba, P and Di Paola, M}, title = {[Pleural mesotheliomas in the Po River valley near Pavia; mortality, incidence and the correlations with an asbestos cement plant].}, journal = {La Medicina del lavoro}, volume = {85}, number = {2}, pages = {157-160}, pmid = {8072444}, issn = {0025-7818}, mesh = {Asbestos/*adverse effects ; Confidence Intervals ; Construction Materials/*adverse effects ; Female ; Humans ; Incidence ; Italy/epidemiology ; Male ; Mesothelioma/epidemiology/etiology/*mortality ; Pleural Neoplasms/epidemiology/etiology/*mortality ; Sex Distribution ; }, abstract = {A spatial cluster of pleural mesothelioma cases was detected in Broni, in the Province of Pavia (northwestern Italy). Eighteen deaths due to malignant pleural neoplasms were observed in the years 1980-87 (SMR: 556; 95% confidence interval: 329-878) and the incidence of pleural mesothelioma in 1980-89 was 9.1 cases per 100,000 person-years among men and 4.3 cases among women. These findings are discussed with reference to the presence in Broni of a plant manufacturing asbestos cement products.}, } @article {pmid8070777, year = {1994}, author = {Yang, J and Luo, S and Liu, X}, title = {[Relationship between effect of sodium selenite on blocking mesothelioma induced by crocidolite and level of serum lipid peroxidation in rats].}, journal = {Hua xi yi ke da xue xue bao = Journal of West China University of Medical Sciences = Huaxi yike daxue xuebao}, volume = {25}, number = {1}, pages = {66-69}, pmid = {8070777}, issn = {0257-7712}, mesh = {Animals ; Asbestos, Crocidolite ; Female ; Lipid Peroxides/blood ; Male ; Mesothelioma/chemically induced/*prevention & control ; Pleural Neoplasms/chemically induced/*prevention & control ; Rats ; Rats, Wistar ; Sodium Selenite/*therapeutic use ; }, abstract = {This paper reports the relationship between the effect of sodium selenite on blocking mesothelioma induced by crocidolite and the level of serum lipid peroxidation in rats. The result showed that sodium selenite solution (5ppm) might not only block and slow down the formation and growth of mesothelioma but also prevent peroxidation produced by crocidolite. The incidence of mesothelioma and the content of LPO in the Se group were lower than those in the positive control group in different periods (0-430 days and 0-530 days respectively). The survival time (341 days) of the first case of mesothelioma and the death peak period (530-630 days) in the Se group were longer than those (237 days and 430-530 days respectively) in the positive group. There was a good correlation between the change of G value in the Se group and the change of G value in the positive control group in different experimental periods (r = 0.9991). These results will provide scientific bases for recognizing the mechanism of mesothelioma and for furthering the practice in the people exposed to asbestos.}, } @article {pmid7941551, year = {1994}, author = {Kotela, I and Blady-Kotela, A}, title = {[Incidence of mesothelioma among asbestos plant workers].}, journal = {Wiadomosci lekarskie (Warsaw, Poland : 1960)}, volume = {47}, number = {5-6}, pages = {161-163}, pmid = {7941551}, issn = {0043-5147}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; *Chemical Industry ; Dust/adverse effects ; Environmental Exposure/*adverse effects ; Humans ; Incidence ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Diseases/*epidemiology/etiology ; Pleural Neoplasms/*epidemiology/etiology ; Poland/epidemiology ; }, abstract = {Pleural mesothelioma is a very rare neoplasm. Its aetiology is connected with exposure to asbestos dust. In the paper 12 cases are presented of pleural mesothelioma out of 34 cases of lung cancer diagnosed in Asbestos-Cement Factory workers and in persons living in the vicinity of this plant. The attention is paid to the increase of incidence of pleural mesothelioma and health risk connected with it for the population of that region, caused by the production of the plant.}, } @article {pmid7510036, year = {1994}, author = {Ohshima, H and Bartsch, H}, title = {Chronic infections and inflammatory processes as cancer risk factors: possible role of nitric oxide in carcinogenesis.}, journal = {Mutation research}, volume = {305}, number = {2}, pages = {253-264}, doi = {10.1016/0027-5107(94)90245-3}, pmid = {7510036}, issn = {0027-5107}, mesh = {Bacterial Infections/complications/epidemiology ; Chronic Disease/*epidemiology ; Free Radicals ; Helicobacter Infections/chemically induced/epidemiology ; Helicobacter pylori ; Humans ; Inflammation/*epidemiology/physiopathology ; Models, Biological ; Neoplasms/*epidemiology/etiology ; Nitric Oxide/*metabolism ; Parasitic Diseases/complications/epidemiology ; Risk Factors ; Virus Diseases/complications/epidemiology ; }, abstract = {Infection by bacteria, parasites or viruses and tissue inflammation such as gastritis, hepatitis and colitis are recognized risk factors for human cancers at various sites. Nitric oxide (NO) and other oxygen radicals produced in infected and inflamed tissues could contribute to the process of carcinogenesis by different mechanisms, which are discussed on the basis of authors' studies on liver fluke infection and cholangiocarcinoma development. A similar mechanism could apply to other suspected and known cancer-causing agents including Helicobacter pylori infection (stomach cancer) or asbestos exposure (lung mesothelioma). Studies on the type of tissue and DNA damage produced by NO and by other reactive oxygen species are shedding new light on the molecular mechanisms by which chronic inflammatory processes may initiate or enhance carcinogenesis in humans.}, } @article {pmid8152111, year = {1994}, author = {Miura, H and Takabe, K and Akabane, H and Kimula, Y}, title = {[Asbestos-related pleural effusion].}, journal = {Ryoikibetsu shokogun shirizu}, volume = {}, number = {3}, pages = {742-745}, pmid = {8152111}, mesh = {Asbestos/*adverse effects ; Asbestosis/complications ; Humans ; Mesothelioma/complications ; Pleural Effusion/*etiology ; }, } @article {pmid8147397, year = {1994}, author = {Tarchi, M and Orsi, D and Comba, P and De Santis, M and Pirastu, R and Battista, G and Valiani, M}, title = {Cohort mortality study of rock salt workers in Italy.}, journal = {American journal of industrial medicine}, volume = {25}, number = {2}, pages = {251-256}, doi = {10.1002/ajim.4700250211}, pmid = {8147397}, issn = {0271-3586}, mesh = {Adult ; Aged ; Cause of Death ; Cohort Studies ; Female ; Humans ; Italy/epidemiology ; Male ; Middle Aged ; *Mining ; *Mortality ; Neoplasms/mortality ; Occupational Diseases/mortality ; Retrospective Studies ; Risk Factors ; Sodium Chloride ; }, abstract = {A cohort mortality study of rock salt workers was carried out in Volterra, Italy. The occupational risk factors identified during environmental hygiene surveys were high noise levels and exposure to dusts and to chrysotile asbestos. The cohort consists of 487 subjects (367 males and 120 females) employed in the mine between 1/1/1965 and 12/31/1989. At the end of follow-up, 387 individuals were alive (295 males and 92 females), and 100 were decreased (72 males and 28 females). For two decedents, the cause of death was unknown. Regional rates were used for the computation of standardized mortality ratios (SMRs). In the entire cohort, observed mortality for all causes was similar to expected (SMR = 98, 100 obs); SMR for all cancer was 127 (41 obs); for lung cancer, the SMR was 146 (10 obs). Two cases of pleural mesothelioma, both in males, resulted in a statistically significant elevation of this cause (SMR = 741, 90% confidence interval (CI) 131-2,332). Two malignant brain tumors were detected (SMR 328, 90% CI 58-1,032); one of these was identified as a secondary neoplasm with consideration of additional clinical information. Among males, mortality for all cancers was significantly increased (SMR = 140, 90% CI 106-192). The observed mortality for malignant tumors of the digestive and the respiratory systems was higher than expected. In women, two cases of malignant ovarian cancer were observed vs. 0.42 expected on the basis of the regional rates. Increased mortality from lung and pleural tumors was consistent with the exposure to asbestos, which has also been shown to play a role in the development of ovarian tumors. The main limitations of this study were the small number of subjects and the definition of exposure solely in terms of duration of employment. Further studies of rock salt workers are needed to elucidate our findings.}, } @article {pmid7802534, year = {1994}, author = {Loire, R and Tabib, A}, title = {[Malignant mesothelioma of the pericardium. An anatomo-clinical study of 10 cases].}, journal = {Archives des maladies du coeur et des vaisseaux}, volume = {87}, number = {2}, pages = {255-262}, pmid = {7802534}, issn = {0003-9683}, mesh = {Aged ; Aged, 80 and over ; Asbestosis/complications ; Diagnostic Imaging ; Female ; Heart Neoplasms/*diagnosis/therapy ; Humans ; Male ; Mesothelioma/*diagnosis/therapy ; Middle Aged ; Pericardiectomy ; *Pericardium ; }, abstract = {Ten pericardial mesotheliomas (8 of which had associated unilateral pleural involvement) were observed over a 22 year period in subjects over 50 years of age. The diagnosis was only confirmed several months after the presenting symptoms (shortness of breath, chest pain), usually by histological studies of pericardial biopsies performed during construction of a pleuro-pericardial window because of tamponade or of pleural biopsy in cases of pleuro-pericardial disease. There is no specific diagnostic feature and even modern imaging methods are unable to distinguish mesothelioma from pericardial tuberculosis. In 7 cases, there were large haemorrhagic pericardial effusions. At present, there is no effective treatment for mesothelioma and the physician's goal is to make the patient's short survival time as comfortable as possible with respect to the severe pain and recurrent pleuro-pericardial effusions. The pericardial mesothelioma is rare (less than 1% compared with 96% pleural and 3% peritoneal localisations) and possibly related to exposure to asbestos, at least in those cases with associated pleural involvement. The authors underline the utility of histological analysis of the utility of histological analysis of the pericardium if only to establish the diagnosis of mesothelioma and to enable administration of curative treatment of other pathologies (tuberculosis, malignant lymphoma) with identical clinical presentations.}, } @article {pmid8521546, year = {1994}, author = {Cipollone, G and Montini, F and Lattanzio, G and Errichi, BM}, title = {[Peritoneal mesothelioma as a rare case of acute abdomen. Review of the literature].}, journal = {Chirurgia italiana}, volume = {46}, number = {6}, pages = {73-79}, pmid = {8521546}, issn = {0009-4773}, mesh = {Abdomen, Acute/*etiology ; Aged ; Humans ; Male ; Mesothelioma/*complications/diagnosis/therapy ; Peritoneal Neoplasms/*complications/diagnosis/therapy ; }, abstract = {Peritoneal mesothelioma is a rare neoplasm with generic and non-specific symptoms. In some cases it is associated with various and particular clinical syndromes. These findings make it so insidious that the diagnosis is rarely make the preoperative course. Usually, there has been previous exposure to asbestos, during even if other causes are reported. Rarely, a peritoneal mesothelioma appears with signs and symptoms suggestive of acute abdomen, such as the present case. On admission the patient presented clinical features apparently requiring emergency surgery. In fact, at laparotomy, the tumour, arising from the mesenterium, had perforated the peritoneal cavity and communicated with the digiunal lumen, causing a septic hemoperitoneum. A radical resection was performed and the continuity of the intestinal tract was restored through an end-to-end entero-anastomosis. The patient, with a history of exposure to asbestos, was alive four years later. But over the last twelve months diffuse metastasis has occurred in the lung and liver, and there was no response to systemic chemotherapy. This case may be considered singular of the clinical syndrome, the long-term survival and the circumscribed aspect of the tumour. Through a review of the literature, the features of the present diagnostic procedure are underlined and the importance of multidisciplinary treatment as the best approach to peritoneal mesothelioma is emphasized.}, } @article {pmid8275722, year = {1994}, author = {Hillerdal, G}, title = {Pleural plaques and risk for bronchial carcinoma and mesothelioma. A prospective study.}, journal = {Chest}, volume = {105}, number = {1}, pages = {144-150}, doi = {10.1378/chest.105.1.144}, pmid = {8275722}, issn = {0012-3692}, mesh = {Adolescent ; Adult ; Aged ; Asbestos ; Asbestosis/diagnostic imaging/epidemiology ; Carcinoma, Bronchogenic/*epidemiology ; Cohort Studies ; Follow-Up Studies ; Humans ; Incidence ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Occupational Exposure/statistics & numerical data ; Pleural Diseases/diagnostic imaging/*epidemiology ; Prospective Studies ; Radiography ; Risk Factors ; Smoking/epidemiology ; Sweden/epidemiology ; Time Factors ; }, abstract = {From the general population in the county of Uppsala, Sweden, 1,596 men with pleural plaques fulfilling strict radiologic criteria were identified from 1963 until June 1985. The men have been followed prospectively for 16,369 person-years. The number of mesotheliomas and bronchial carcinomas was compared with the age- and year-specific expected incidence from the official cancer registry of Sweden. Fifty bronchial carcinomas occurred, while 32.1 were expected after correction for smoking habits, a difference which was statistically significant. Patients with radiologic asbestosis were overrepresented among those with bronchial carcinoma. The risk for patients with pleural plaques without asbestosis was increased 1.4 times, which was statistically significant. There were 9 mesotheliomas, while only 0.8 were expected. The mean latency time from first exposure to diagnosis of bronchial cancer was 44.1 years and for mesothelioma was 48.1 years. Thus, pleural plaques on the chest roentgenogram indicate significant exposure to asbestos, with an increased risk for mesothelioma and possibly also for bronchial carcinoma. Any person found to have plaques on chest roentgenogram should be informed of them and should be persuaded to stop smoking.}, } @article {pmid8198827, year = {1994}, author = {Marczynski, B and Czuppon, AB and Marek, W and Reichel, G and Baur, X}, title = {Increased incidence of DNA double-strand breaks and anti-ds DNA antibodies in blood of workers occupationally exposed to asbestos.}, journal = {Human & experimental toxicology}, volume = {13}, number = {1}, pages = {3-9}, doi = {10.1177/096032719401300102}, pmid = {8198827}, issn = {0960-3271}, mesh = {Adult ; Aged ; Antibodies, Antinuclear/*blood ; Asbestos/*adverse effects ; DNA/analysis/*drug effects ; *DNA Damage ; Densitometry ; Electrophoresis, Gel, Pulsed-Field ; Humans ; Leukocytes/drug effects/metabolism ; Male ; Middle Aged ; Occupational Exposure/*analysis ; }, abstract = {Asbestos, proven to be carcinogenic in humans and animals, is reported to have no genotoxic effect. Asbestos workers have an increased risk of lung cancer, mesothelioma, and other tumours. Earlier findings showed that crocidolite can induce DNA strand breaks in cultured rat embryo cells as assessed by nick translation. We investigated DNA double-strand breaks in white blood cells (WBC) of ten workers occupationally exposed to asbestos. According to our results, obtained with neutral filter elution, individuals who had been exposed to asbestos fibres showed two to four times more DNA double-strand breaks (dsb) in white blood cells than ten non-exposed persons. The induced DNA fragments are of about 250 kb (compared to chromosomal DNA of Saccharomyces cerevisiae standard marker). Using additionally the chromosomal DNA protective method of agarose-plugs, DNA fragments in the range of 200 to 1000 kb have been found in the white blood cells of the same ten workers occupationally exposed to asbestos. In the white blood cells of non-exposed subjects no DNA fragments could be detected with this method. Compared to 51 non-exposed persons, elevated anti-ds DNA antibody concentrations were found in ten workers occupationally exposed to asbestos. The fact that workers occupationally exposed to asbestos have distinctly more double-strand breaks and anti-ds DNA antibodies could mean that an increased incidence of DNA-fragments may be an important indicator in the chronic effect of asbestos-associated carcinogenesis. Apparently, the chronic effects of asbestos observed here do not seem to be identical with that of previously reported acute in vitro effects.}, } @article {pmid8161898, year = {1994}, author = {Smith, TR}, title = {Malignant peritoneal mesothelioma: marked variability of CT findings.}, journal = {Abdominal imaging}, volume = {19}, number = {1}, pages = {27-29}, pmid = {8161898}, issn = {0942-8925}, mesh = {Aged ; Aged, 80 and over ; Ascites/etiology ; Female ; Humans ; Male ; Mesothelioma/complications/*diagnostic imaging ; Middle Aged ; Peritoneal Neoplasms/complications/*diagnostic imaging ; Tomography, X-Ray Computed ; }, abstract = {Three pathologically proven cases of malignant peritoneal mesothelioma (MPM) are shown with markedly different computed tomographic (CT) appearances. The first presented as a large enhancing pancreatic mass, a second with diffuse solid large intraperitoneal masses enveloping bowel and mesentery, and a third with predominance of ascites and small peritoneal nodules. In only one patient was there a history of possible asbestos exposure. The CT findings, pathology, and differential diagnosis of MPM are discussed.}, } @article {pmid8138558, year = {1994}, author = {Hartmann, CA and Schütze, H}, title = {Mesothelioma-like tumors of the pleura: a review of 72 autopsy cases.}, journal = {Journal of cancer research and clinical oncology}, volume = {120}, number = {6}, pages = {331-347}, pmid = {8138558}, issn = {0171-5216}, mesh = {Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Autopsy ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; Male ; Mesothelioma/*pathology/secondary ; Middle Aged ; Neoplasm Metastasis ; Neoplasms, Unknown Primary/pathology ; Pleural Neoplasms/*pathology/secondary ; Retrospective Studies ; Sex Distribution ; }, abstract = {The 72 mesothelioma-like tumors of the pleura (MLTP) found among 33 500 autopsy cases collected over more than 30 years are reviewed. MLTP have a worse prognosis than the 106 cases of pleural mesothelioma autopsied in our institutes with regard to survival time and metastatic spread. In MLTP, adenocarcinomas predominate with a wide range of histological and cytological variation and prominent development of connective tissue having its origin in the periphery of the lung. These intrapulmonary primary tumors often fulfill the criteria of pulmonary scar cancer. Etiologically, there is no correlation between the origin of this tumor and smoking or exposure to asbestos. The absence of mucus formation and glandular differentiation, together with the presence of spindle-shaped carcinoma components and strong mesothelial or stroma proliferation, can make the differential diagnosis between this tumor type and mesothelioma difficult. Immunohistological investigations were performed on 11 cases with antibodies against intermediate filament proteins, vascular endothelium, collagen IV, macrophage antigens, carcinoembryonic antigen (CEA), LeuM1, and the antibody BerEP4. Our investigation shows that a battery of several tumor markers, such as antibodies against LeuM1, CEA, and the antibody BerEP4, as well as staining with periodic acid/Schiff/diastase discriminate primary from secondary pleural neoplasms, whilst intermediate filament proteins alone are of little diagnostic value.}, } @article {pmid8131096, year = {1994}, author = {Huncharek, M}, title = {Asbestos and cancer: epidemiological and public health controversies.}, journal = {Cancer investigation}, volume = {12}, number = {2}, pages = {214-222}, doi = {10.3109/07357909409024876}, pmid = {8131096}, issn = {0735-7907}, mesh = {Air Pollutants ; Animals ; Asbestos/*adverse effects ; Construction Materials ; Environmental Exposure/*adverse effects ; Humans ; Lung Neoplasms/epidemiology/*etiology ; Mesothelioma/*etiology ; Risk Factors ; }, abstract = {This paper discusses many of the currently controversial issues surrounding asbestos health effects and their relationship to cancer risk assessment and risk management. The major conclusions reached from this analysis are: (1) All asbestos fiber types are carcinogenic and pose a threat to human health. Therefore, all fiber types should be regulated similarly. (2) The health risks associated with indoor asbestos exposure are uncertain. Available data show that some groups, such as building maintenance personnel (among others), may contract asbestos-related diseases secondary to indoor exposure. Clearly, additional research is needed to accurately determine the extent and nature of disease risk under these conditions. (3) Controlled use has proved an elusive goal. Limited information from underdeveloped countries parallels the experience of Western industrialized nations. Efforts by the Canadian government to establish markets for asbestos in these areas should be opposed. (4) Finally, asbestos-related cancer risk is no longer confined to asbestos industry workers. Asbestos-related mesothelioma has been documented in a wide variety of occupational and nonoccupational settings, highlighting the need for continued surveillance to minimize potential health risks.}, } @article {pmid8117151, year = {1994}, author = {Murai, Y and Kitagawa, M and Yasuda, M and Okada, E and Koizumi, F and Miwa, A}, title = {Asbestos fiber analysis in seven asbestosis cases.}, journal = {Archives of environmental health}, volume = {49}, number = {1}, pages = {67-72}, doi = {10.1080/00039896.1994.9934418}, pmid = {8117151}, issn = {0003-9896}, mesh = {Adult ; Aged ; Asbestos/adverse effects/*isolation & purification ; Asbestosis/etiology/*physiopathology ; Female ; Humans ; Lung/*physiopathology ; Male ; Middle Aged ; *Occupational Exposure ; Smoking/adverse effects ; }, abstract = {Asbestos bodies and fibers deposited in the lungs of seven asbestosis cases were counted after tissue digestion. The types and sizes of 100 asbestos fibers for each case were also analyzed. Asbestos bodies were counted with an optical microscope at 100x magnification, and asbestos fibers were counted with a transmission electron microscope (TEM) at 2000x magnification. Most asbestos fibers detected with TEM were longer than 3 microns (92.5%) and thicker than 0.1 microns (92.3%). Short fibers less than 2 microns--both chrysotile and amphiboles, as well as long, thin fibers less than 0.06 microns--would be missed at 2000x (TEM). An average of 1.37 (0.081-5.5) x 10(6) asbestos bodies and 164.8 (0.55-610) x 10(6) asbestos fibers per 5 g wet (0.88 g dry) lung tissue were found, and these values are higher than what was reported in mesothelioma cases without asbestosis that were reported previously. More than 13 (average = 266.2) asbestos bodies were found in a 4-micron-thick tissue section (average area = 3.24 cm2). One asbestos body in a section equaled approximately 5,000 per 5 g wet lung tissue. The intensity of fibrosis was minimal in one case, mild in four, moderate and severe in one each, and the intensity was correlated with the number of asbestos bodies and fibers. The fibrosis in the severe case may have been intensified by repeated infection. Crocidolite fibers were found most frequently (84.7%), were thin, and had a high aspect ratio by our counting rules. Crocidolite with a high aspect ratio may be most fibrogenic in the lung.}, } @article {pmid8088896, year = {1994}, author = {Aravindan, KP and Rajeevan, K and Jose, L}, title = {Malignant mesothelioma of the pleura in a young shipyard worker.}, journal = {Indian journal of pathology & microbiology}, volume = {37}, number = {1}, pages = {113-115}, pmid = {8088896}, issn = {0377-4929}, mesh = {Adult ; Asbestos/*adverse effects ; Humans ; Male ; Mesothelioma/*pathology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*pathology ; *Ships ; }, } @article {pmid8061543, year = {1994}, author = {Thomason, R and Schlegel, W and Lucca, M and Cummings, S and Lee, S}, title = {Primary malignant mesothelioma of the pericardium. Case report and literature review.}, journal = {Texas Heart Institute journal}, volume = {21}, number = {2}, pages = {170-174}, pmid = {8061543}, issn = {0730-2347}, mesh = {Adult ; Female ; Heart Neoplasms/diagnosis/*epidemiology/surgery ; Humans ; Mesothelioma/diagnosis/*epidemiology/surgery ; Pericardium/*pathology ; }, abstract = {Pericardial mesothelioma is a highly lethal and fortunately rare cardiac neoplasm. We present the clinical and pathologic features of a primary sarcomatoid mesothelioma. To better understand the clinical, radiographic, and pathologic features of this entity, we reviewed 27 cases described in the English literature from 1972 through 1992, which, together with our case, provided a total of 28 cases. Findings of the review include a male-female ratio of 2:1, a wide age range (12 to 77 years; mean, 47 years), and documented asbestos exposure in 4 of 28 (14%) patients. Commonly used imaging studies do not appear to offer great sensitivity, for a mass was detected by echocardiography in only 2 of 16 (12%) patients and by computed tomography in 4 of 9 (44%). Pathologic findings revealed a diffuse growth pattern in most cases (18 of 25, or 72%), together with an equal distribution between the biphasic, epithelioid, and sarcomatoid variants. Effusion cytology revealed malignant cells in only 2 of 10 (20%) cases. With or without therapy, prognosis was uniformly poor, since 24 of 27 patients were dead of the disease at the time the reports were published.}, } @article {pmid7990627, year = {1994}, author = {Vorpahl, U and Buhr, J and Bohle, RM and Berghäuser, KH and Henneking, K}, title = {[Localized benign pleural mesothelioma].}, journal = {Langenbecks Archiv fur Chirurgie}, volume = {379}, number = {5}, pages = {307-309}, pmid = {7990627}, issn = {0023-8236}, mesh = {Female ; Humans ; Mesothelioma/diagnostic imaging/pathology/*surgery ; Middle Aged ; Pleura/pathology ; Pleural Neoplasms/diagnostic imaging/pathology/*surgery ; Thoracotomy ; Tomography, X-Ray Computed ; }, abstract = {Benign mesothelioma of the pleura is a very rare tumor. The cells responsible originate from either the mesothelium or the submesothelium. This is why such tumors are described in the literature as fibroma of the pleura, mesothelial fibroma, localized fibrous mesothelioma and monophasic spindle cell tumor. Their growth, is very slow taking several years or even decades. In contrast to the more common malignant mesothelioma of the pleura, it is not related to asbestos exposure. This report deals with a 47-year-old woman patient with a giant benign mesothelioma of the pleura in the region of the right thorax, which was completely removed by thoracotomy.}, } @article {pmid7927845, year = {1994}, author = {Giaroli, C and Belli, S and Bruno, C and Candela, S and Grignoli, M and Minisci, S and Poletti, R and Riccò, G and Vecchi, G and Venturi, G}, title = {Mortality study of asbestos cement workers.}, journal = {International archives of occupational and environmental health}, volume = {66}, number = {1}, pages = {7-11}, pmid = {7927845}, issn = {0340-0131}, mesh = {Asbestos/*adverse effects ; Asbestosis/*mortality ; *Cause of Death ; Cohort Studies ; Construction Materials/*adverse effects ; Follow-Up Studies ; Humans ; Italy/epidemiology ; Life Tables ; Lung Neoplasms/*mortality ; Mesothelioma/*mortality ; Neoplasms/mortality ; Pleural Neoplasms/*mortality ; }, abstract = {The present study describes cause-specific mortality of asbestos cement workers in the Emilia Romagna region of Italy. The cohort included workers in ten factories, most of which started operating between 1955 and 1965. Asbestos, mainly chrysotile, constituted 10%-20% of the dry component of the mixture. Crocidolite range between 5% and 50% of total asbestos. Asbestos concentrations up to 44 ff/cc were reported prior to 1975, while in recent years they have usually been below 0-1 ff/cc. The cohort included 3341 workers who had at some time been employed in the ten factories under study. Their mortality experience was compared with that of the population resident in Emilia Romagna. Vital status was ascertained at 1989. Seventy-three subjects were lost to follow-up (2.2%). Mortality from all causes and from all types of cancer was increased in the cohort. Malignant neoplasms of the respiratory tract showed a significant increase (SMR: 134; 90% confidence interval: 101-175; 40 observed) due to lung cancer (SMR: 124; 90% confidence interval: 91-166; 33 observed) and neoplasms of the pleura, mediastinum, and other parts of the respiratory tract (SMR: 602; 90% confidence interval 237-1267; 5 observed). The discrepancy between observed and expected mortality mainly concerned subjects with at least 20 years of employment in the factories. Five more cases of histologically confirmed mesothelioma occurred after the end of follow-up.}, } @article {pmid7832417, year = {1994}, author = {Bianchi, C}, title = {[Malignant mesothelioma: various key aspects].}, journal = {Annali dell'Istituto superiore di sanita}, volume = {30}, number = {2}, pages = {253-256}, pmid = {7832417}, issn = {0021-2571}, mesh = {Asbestos/*adverse effects ; Humans ; Lung Neoplasms/diagnosis/*etiology/prevention & control ; Mesothelioma/diagnosis/*etiology/prevention & control ; }, abstract = {Mesothelioma deserves particular attention for various reasons: 1) a dramatic increase in the incidence of this tumor has been observed in various countries; 2) diagnosis is not rarely problematic; 3) asbestos-related mesothelioma represents a nearly unique model in human cancerogenesis. Latency periods (defined as intervals between first exposure to asbestos and death) differ from one occupational category to another. These differences seem to depend not only on the intensity of the exposure, but also on other unidentified factors. The study of the mechanisms influencing the length of latency periods could open a way in preventing mesothelioma.}, } @article {pmid7708941, year = {1994}, author = {Sarić, M and Vujović, M}, title = {Malignant tumors in an area with an asbestos processing plant.}, journal = {Public health reviews}, volume = {22}, number = {3-4}, pages = {293-303}, pmid = {7708941}, issn = {0301-0422}, mesh = {Adult ; Air Movements ; *Air Pollutants ; Asbestos/*adverse effects ; Cohort Studies ; Croatia/epidemiology ; Environmental Monitoring ; Epidemiological Monitoring ; Female ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; Neoplasms/epidemiology/*etiology ; }, abstract = {Incidence rate of malignant tumors of the lung/bronchus, pleura, larynx, pharynx, and peritoneum during the period 1974 to 1987 was studied in a Croatian coastal area with an asbestos processing plant which started to operate in 1954. The study area covers 169 km2 with 11,270 inhabitants: 5590 men and 5710 women (average number during the study period). The calculated number of inhabitants aged 35 and older was 4639 (41.1%), 11.5% were aged 60 or older, and the average age was 32 years. Over the observed 14-year period there were 51 cases of malignant tumors, 40 in men and 11 in women: lung/bronchus cancer, 36-29 men and 7 women; mesothelioma, 5-2 men and 3 women; laryngeal cancer, 5 men; pharyngeal cancer, 4-3 men and 1 women; and peritoneal cancer, 1 man. The results of the study showed that the incidence of lung/bronchus cancer in the studied population was half that in Croatia. There were also fewer malignant tumors of the pharynx and peritoneum in this area than in Croatia. On the other hand, the incidence of primary tumors of the pleura was more than 5 times as high and of laryngeal tumors more than 2 times as high as in Croatia. Evaluation of the data showed that distance from the source of emissions was not crucial for the development of tumors. The incidence of the tumors in the town with the asbestos factory was the lowest. Among and within different towns/villages the tumor incidence varied; in some the observed rate was higher than the expected rate. A more detailed analysis indicated a possible influence of the relief and prevailing wind direction on the environmental contamination with asbestos from the emissions source and consequently on an uneven distribution of the tumor incidence among separate settlements in the area under study.}, } @article {pmid7701214, year = {1994}, author = {Brousse, D and Sonneville, A}, title = {[Pleural fibroma: a case of a patient exposed to tungsten carbide and asbestos].}, journal = {Revue de pneumologie clinique}, volume = {50}, number = {6}, pages = {333-337}, pmid = {7701214}, issn = {0761-8417}, mesh = {Asbestos/*adverse effects ; Humans ; Male ; Mesothelioma/*etiology/pathology ; Middle Aged ; Pleural Neoplasms/*etiology/pathology ; Tungsten Compounds/*adverse effects ; }, abstract = {We report here a case of localized fibrous pleural mesothelioma diagnosed in a sixty-year old patient, who had been exposed to tungsten carbide and asbestos dust for almost twenty years. He first consulted because of enduring lateral chest pains combined with progressive and increasing dyspnea on exertion. The initial diagnosis, after both pulmonary radiograph and computerised tomography, was confirmed by a histology which revealed fusiform cells of fibroblastic origin. After simple and total excision of the tumor, symptoms improved.}, } @article {pmid7659001, year = {1994}, author = {Olmedo, G and Poleri, C and Rojas, O and Abdala, O}, title = {[Rounded atelectasis: another pulmonary pseudotumor].}, journal = {Medicina}, volume = {54}, number = {6}, pages = {641-645}, pmid = {7659001}, issn = {0025-7680}, mesh = {Biopsy, Needle ; Humans ; Male ; Middle Aged ; Pulmonary Atelectasis/diagnostic imaging/*pathology ; Tomography, X-Ray Computed ; }, abstract = {Rounded atelectasis or Blesovsky's syndrome (also called pleuroma, folded lung or shrinking pleuritis with atelectasis) is the association of plaque-like pleural fibrosis with a folding visceral pleura and nodular atelectasis of the underlying lung. It can mimic a peripheral lung tumor or a mesothelioma. Radiography and computed tomography (CT) show a characteristic opacity with a comet-tail sign. The pathogenesis in some of the cases is considered to be secondary to pleural effusions and in others to a contraction of a focus of pleural fibrosis, not associated with effusion. In many cases, there was a history of asbestos exposure. We report the case of a 44-year-old, man who had smoked and worked with materials containing asbestos. He referred thoracic pain of 6 months duration and dyspnea. An X-ray of the chest (Fig. 1, 2) and a CT scan (Fig. 3) revealed a round peripheral mass in the left lower lobe. A fine needle aspiration biopsy of the lung was performed revealing clusters of large atypical cells with abundant cytoplasm. A thoracotomy was decided upon and no frozen section was requested. Gross examination of the resected lobe (Fig. 4) demonstrated a 2.5 cm white, irregular, firm and retracting pleural plaque. On sectioning, a peculiar folding of the visceral pleura delimited by anthracotic pigmentation was noted below the fibrotic plaque. The folding extended perpendicularly deep into the parenchyma. It was possible to separate the folding and liberate the underlying parenchyma, which was firm, fibrotic and atelectatic. No tumor was found anywhere within the lobe.(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid7555762, year = {1994}, author = {Leino, T and Karjalainen, A and Anttila, S}, title = {[Asbestos-associated cancer as an occupational disease].}, journal = {Duodecim; laaketieteellinen aikakauskirja}, volume = {110}, number = {18}, pages = {1713-1717}, pmid = {7555762}, issn = {0012-7183}, mesh = {Aged ; Asbestosis/*complications ; Finland ; Humans ; Lung Neoplasms/economics/*etiology ; Male ; Mesothelioma/economics/*etiology ; Middle Aged ; Workers' Compensation ; }, } @article {pmid8311096, year = {1993}, author = {Webster, I and Goldstein, B and Coetzee, FS and van Sittert, GC}, title = {Malignant mesothelioma induced in baboons by inhalation of amosite asbestos.}, journal = {American journal of industrial medicine}, volume = {24}, number = {6}, pages = {659-666}, doi = {10.1002/ajim.4700240602}, pmid = {8311096}, issn = {0271-3586}, mesh = {Animals ; Asbestos, Amosite/*adverse effects ; Atmosphere Exposure Chambers ; Dust ; Environmental Exposure ; Male ; Mesothelioma/*etiology/pathology ; Papio ; Peritoneal Neoplasms/*etiology/pathology ; Pleural Neoplasms/*etiology/pathology ; }, abstract = {Ten out of 12 South African baboons (Papio ursinus) survived exposure to amosite asbestos dust for periods ranging from 242 days to 898 days at an aerosol level ranging between 1,100 and 1,200 fibers per milliliter. After exposure, they were kept under observation until they died; the total residence time of amosite varied from 1.2-10.2 years. All underwent detailed postmortem necropsy examinations. All baboons had asbestosis. Five of the baboons developed malignant diffuse mesothelioma; three peritoneal, and two pleural with peritoneal invasion. These results indicate that amosite is highly carcinogenic. Since it is difficult to accomplish follow-up of persons exposed to amosite asbestos because of the geographic location of the amosite mines and mills in South Africa (a majority of the workers being migrant laborers from countries bordering on the Transvaal), it is therefore probable that cases of peritoneal mesothelioma have been missed. If human beings are likely to react to amosite as do baboons, epidemiological follow-up should include identification of abdominal as well as thoracic neoplasms.}, } @article {pmid8280640, year = {1993}, author = {Danielsen, TE and Langård, S and Andersen, A and Knudsen, O}, title = {Incidence of cancer among welders of mild steel and other shipyard workers.}, journal = {British journal of industrial medicine}, volume = {50}, number = {12}, pages = {1097-1103}, pmid = {8280640}, issn = {0007-1072}, mesh = {Adolescent ; Adult ; Age Distribution ; Aged ; Asbestos/adverse effects ; Cohort Studies ; Humans ; Incidence ; Lung Neoplasms/*epidemiology ; Male ; Middle Aged ; Neoplasms/epidemiology ; Norway/epidemiology ; Occupational Diseases/*epidemiology ; *Ships ; Smoking/adverse effects ; Time Factors ; *Welding ; }, abstract = {The incidence of cancer among 4571 shipyard workers with first employment between 1940 and 1979, including 623 welders of mild steel, was investigated in a historical cohort study. The loss to follow up was 1.1%. The total number of deaths was 1078 (974.5 expected) and there were 408 cases of cancer v 361.3 expected. Sixty five cases of lung cancer were found v 46.3 expected based on the national rates for males. Four pleural mesotheliomas had occurred (1.2 expected), none among the welders. An excess of lung cancers was found among the welders (nine cases v 3.6 expected). There were six cases of lung cancer v 1.6 expected in a high exposure group of 255 welders. A survey of the smoking habits as of 1984 indicated 10%-20% more daily smokers among the shipyard production workers than among Norwegian males. Exposure to smoking and asbestos were confounding variables in this study.}, } @article {pmid8280638, year = {1993}, author = {McDonald, JC and Liddell, FD and Dufresne, A and McDonald, AD}, title = {The 1891-1920 birth cohort of Quebec chrysotile miners and millers: mortality 1976-88.}, journal = {British journal of industrial medicine}, volume = {50}, number = {12}, pages = {1073-1081}, pmid = {8280638}, issn = {0007-1072}, mesh = {Aged ; Aged, 80 and over ; *Asbestos, Serpentine ; Asbestosis/*mortality ; Cause of Death ; Cohort Studies ; Humans ; Lung Neoplasms/mortality ; Male ; Mesothelioma/mortality ; Middle Aged ; *Mining ; *Occupational Exposure ; Quebec/epidemiology ; Smoking/mortality ; Time Factors ; }, abstract = {A cohort of some 11,000 men born 1891-1920 and employed for at least one month in the chrysotile mines and mills of Quebec, was established in 1966 and has been followed ever since. Of the 5351 men surviving into 1976, only 16 could not be traced; 2508 were still alive in 1989, and 2827 had died; by the end of 1992 a further 698 were known to have died, giving an overall mortality of almost 80%. This paper presents the results of analysis of mortality for the period 1976 to 1988 inclusive, obtained by the subject-years method, with Quebec mortality for reference. In many respects the standardised mortality ratios (SMRs) 20 years or more after first employment were similar to those for the period 1951-75--namely, all causes 1.07 (1951-75, 1.09); heart disease 1.02 (1.04); cerebrovascular disease 1.06 (1.07); external causes 1.17 (1.17). The SMR for lung cancer, however, rose from 1.25 to 1.39 and deaths from mesothelioma increased from eight (10 before review) to 25; deaths from respiratory tuberculosis fell from 57 to five. Among men whose exposure by age 55 was at least 300 million particles per cubic foot x years (mpcf.y), the SMR (all causes) was elevated in the two main mining regions, Asbestos and Thetford Mines, and for the small factory in Asbestos; so were the SMRs for lung cancer, ischaemic heart disease, cerebrovascular disease, and respiratory disease other than pneumoconiosis. Except for lung cancer, however, there was little convincing evidence of gradients over four classes of exposure, divided at 30, 100, and 300 mpcf.y. Over seven narrower categories of exposure up to 300 mpcf.y the SMR for lung cancer fluctuated around 1.27 with no indication of trend, but increased steeply above that level. Mortality form pneumoconiosis was strongly related to exposure, and the trend for mesothelioma was not dissimilar. Mortality generally was related systematically to cigarette smoking habit, recorded in life from 99% of survivors into 1976; smokers of 20 or more cigarettes a day had the highest SMRs not only for lung cancer but also for all causes, cancer of the stomach, pancreas, and larynx, and ischaemic heart disease. For lung cancer SMRs increased fivefold with smoking, but the increase with dust exposure was comparatively slight for non-smokers, lower again for ex-smokers, and negligible for smokers of at least 20 cigarettes a day; thus the asbestos-smoking interaction was less than multiplicative. Of the 33 deaths from mesothelioma in the cohort to date, 28 were in miners and millers and five were in employees of a small asbestos products factory where commercial amphiboles had also been used. Preliminary analysis also suggest that the risk of mesothelioma was higher in the mines and mills at Thetford Mines than in those at Asbestos. More detailed studies of these differences and of exposure-response relations for lung cancer are under way.}, } @article {pmid8249778, year = {1993}, author = {Lordi, GM and Reichman, LB}, title = {Pulmonary complications of asbestos exposure.}, journal = {American family physician}, volume = {48}, number = {8}, pages = {1471-1477}, pmid = {8249778}, issn = {0002-838X}, mesh = {*Asbestos ; *Asbestosis/diagnosis/epidemiology/etiology/pathology ; Biopsy ; Humans ; *Lung Neoplasms/diagnosis/epidemiology/etiology/pathology ; Medical History Taking ; *Mesothelioma/diagnosis/epidemiology/etiology/pathology ; *Occupational Diseases/chemically induced/diagnosis/epidemiology/pathology ; *Pleural Neoplasms/diagnosis/epidemiology/etiology/pathology ; Public Health ; Respiratory Sounds ; Risk Factors ; Smoking/adverse effects ; Time Factors ; Vital Capacity ; }, abstract = {Except for benign pleural effusion, asbestos-related pulmonary complications, including asbestosis, malignant mesothelioma and bronchogenic carcinoma, usually occur more than 20 years after exposure. Pleural plaques and pleural thickening serve as markers for asbestos exposure, but they are not associated with an increased risk of malignancy. Clinical criteria for the diagnosis of asbestosis include a reliable history of asbestos exposure, an appropriate interval between exposure and disease detection, radiographic evidence of pulmonary fibrosis, decreased vital capacity and diffusing capacity, and bilateral posterior inspiratory crackles. A lung biopsy is indicated only to rule out other causes of interstitial lung disease. A history of dyspnea, pleuritic chest pain, fatigue, weight loss and pleural effusion in a former asbestos worker is suggestive of mesothelioma. Cigarette smoking greatly increases the risk of lung cancer in asbestos workers.}, } @article {pmid8124311, year = {1993}, author = {Nardini, S}, title = {Asbestos and malignant mesothelioma.}, journal = {Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace}, volume = {48}, number = {6}, pages = {676}, pmid = {8124311}, issn = {1122-0643}, mesh = {Asbestos/*adverse effects ; Female ; Humans ; Lung Neoplasms/etiology ; Male ; Mesothelioma/*etiology ; Pleural Neoplasms/etiology ; }, } @article {pmid8113917, year = {1993}, author = {Schuman, LD and Infante, PF}, title = {Synthetic mineral fibers.}, journal = {Journal of occupational medicine. : official publication of the Industrial Medical Association}, volume = {35}, number = {12}, pages = {1173-1177}, pmid = {8113917}, issn = {0096-1736}, mesh = {Air Pollutants, Occupational/*toxicity ; Animals ; Asbestos/*toxicity ; Calcium Compounds/*toxicity ; Cricetinae ; *Glass ; Lung Neoplasms/*etiology ; Maximum Allowable Concentration ; Mesothelioma/*etiology ; Pleural Neoplasms/*etiology ; Rats ; Risk Factors ; Silicates/*toxicity ; }, } @article {pmid8255110, year = {1993}, author = {}, title = {[Mortality from pleural mesothelioma in the province of Barcelona].}, journal = {Medicina clinica}, volume = {101}, number = {15}, pages = {565-569}, pmid = {8255110}, issn = {0025-7753}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Child ; Child, Preschool ; Environmental Exposure/adverse effects ; Female ; Humans ; Infant ; Male ; Mesothelioma/etiology/*mortality ; Middle Aged ; Occupational Exposure/adverse effects ; Pleural Neoplasms/etiology/*mortality ; Spain/epidemiology ; }, abstract = {BACKGROUND: Pleural mesothelioma is a tumor of low incidence whose relation with the exposure to asbestos has been widely demonstrated. This exposure is generally occupational, but may also be domestic and there is the possibility of environmental exposure.

METHODS: By death certifications all the cases of death by pleural mesothelioma residing in the province of Barcelona from 1983-1990 have been identified. The rates of direct or indirect mortality (standardized by age and sex) (cause of standard mortality) for all the municipalities of the province with some case of mesothelioma over the period studied were calculated. The geographic localization of the companies using asbestos in the province of Barcelona has been obtained, being classified into 6 groups according to the productive subsector to which they belong.

RESULTS: The rate of mortality per 100,000 inhabitants from 1983-1990 was 0.83 for males and 0.47 for females. The calculation of the cause of standard mortality for the municipalities of the province has shown an statistically significant increase in the risk of pleural mesothelioma for El Prat de Llobregat (ratio of standard mortality: 355.1) and Cerdanyola (ratio of standard mortality 313.9) where the companies producing fibrocement are located.

CONCLUSIONS: Part of the cases of pleural mesothelioma in the province of Barcelona may not be due to direct occupational exposure; thus there may be important domestic and/or environmental exposure.}, } @article {pmid8242873, year = {1993}, author = {Carthew, P and Edwards, RE and Dorman, BM and Brown, RC and Hoskins, JA and Simpson, CF}, title = {A reappraisal of the carcinogenicity of surface modified asbestos fibres.}, journal = {Carcinogenesis}, volume = {14}, number = {11}, pages = {2413-2414}, doi = {10.1093/carcin/14.11.2413}, pmid = {8242873}, issn = {0143-3334}, mesh = {Animals ; Asbestos, Amosite/*toxicity ; Male ; Mesothelioma/*chemically induced/pathology ; Pleural Neoplasms/*chemically induced/pathology ; Rats ; Rats, Wistar ; Silanes/*toxicity ; Time Factors ; }, abstract = {A previous study using intrapleural administration of surface-modified amosite asbestos showed a difference in the number of pleural mesotheliomas induced with C18-hydrocarbon derivatised fibres compared to native amosite asbestos. The study has been repeated with larger groups of animals (30) under specific pathogen free conditions, resulting in an increase in the mean animal survival time for both fibre-treated groups. Under these conditions there was no significant difference between the numbers of pleural mesotheliomas induced by C18 hydrocarbon-modified amosite asbestos and native amosite asbestos. The major difference between the two studies was the mean time to death from tumour of rats exposed to fibres. The C18 amosite treated rats in the first study may not have had a mean survival time long enough to allow mesotheliomas to develop.}, } @article {pmid8237983, year = {1993}, author = {Andersen, A and Glattre, E and Johansen, BV}, title = {Incidence of cancer among lighthouse keepers exposed to asbestos in drinking water.}, journal = {American journal of epidemiology}, volume = {138}, number = {9}, pages = {682-687}, doi = {10.1093/oxfordjournals.aje.a116905}, pmid = {8237983}, issn = {0002-9262}, mesh = {Asbestos/*adverse effects ; Cohort Studies ; Follow-Up Studies ; Gastrointestinal Neoplasms/chemically induced/*epidemiology ; Humans ; Incidence ; Male ; Norway/epidemiology ; Occupational Diseases/chemically induced/*epidemiology ; Occupational Exposure/adverse effects ; *Water Supply ; }, abstract = {The study population comprises 690 Norwegian male lighthouse keepers whose water supply came from cisterns that received rain water off asbestos-cement-tiled roofs. The asbestos-cement tiles were installed in the late 1950s, and two decades later the fiber content in the tap water was analyzed. The fiber content ranged from 1,760 to 71,350 million fibers per liter, which is significantly higher than measured in any other Norwegian public water supply. During the follow-up period, 1960-1991, no statistically significant excess risk was found for any type of cancer in the group with a latency period of 20 years or more, except for stomach cancer (11 observed cases vs. 4.57 expected, standardized incidence ratio = 241, 95% confidence interval 120-431). No cases of malignant mesothelioma were found. The study is limited by lack of knowledge as to when the tiles began to deteriorate and, thus, the magnitude of total exposure as well as by the inability to control for such potential confounding factors as diet.}, } @article {pmid7694791, year = {1993}, author = {Hansteen, IL and Hilt, B and Lien, JT and Skaug, V and Haugen, A}, title = {Karyotypic changes in the preclinical and subsequent stages of malignant mesothelioma: a case report.}, journal = {Cancer genetics and cytogenetics}, volume = {70}, number = {2}, pages = {94-98}, doi = {10.1016/0165-4608(93)90174-k}, pmid = {7694791}, issn = {0165-4608}, mesh = {Aged ; Animals ; *Chromosome Aberrations ; Chromosome Banding ; Female ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Karyotyping ; Keratins/biosynthesis ; Male ; Mesothelioma/*genetics/metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Pleural Effusion, Malignant/*genetics ; Polyploidy ; Tumor Cells, Cultured ; }, abstract = {The karyotypic evolution was evaluated in cells from recurring pleural effusions in a patient previously exposed to asbestos. Pleural malignant mesothelioma (MM) was diagnosed 4 years after the first cytogenetic examination. The primary cytogenetic changes consisted of loss of chromosomes 1p,14,21, Y, both 22, and derivative chromosomes involving 1, 2, and 14. The modal chromosome number was 44. Sixty-seven percent of the cells had a normal karyotype. After 4 years of spontaneous remission, only 6% of the cells had a normal karyotype, 42% had the same karyotypic changes as found previously, whereas 52% had additional derivative chromosomes involving chromosomes 1, 3, 5, 7, 8, and 12, trisomy 7, 7p, and 11, and partial or whole monosomy 3, 8, and 9. The chromosomal changes are in agreement with the main findings in previous reports. The karyotype remained quite stable for 7 months in vitro. After 23 months in culture, all the cells were near-triploid. Cells established in culture were cytokeratin positive. All derivative and marker chromosomes identified in the cultured cells had previously been observed in direct preparations from the pleural effusions. We conclude that chromosomes 1, 14, 21, and 22 may be involved in the preclinical stage of development of asbestos-induced mesothelioma, whereas the later chromosomal changes may be related to progression of the tumor.}, } @article {pmid8250061, year = {1993}, author = {Burkhart, G and Schulte, PA and Robinson, C and Sieber, WK and Vossenas, P and Ringen, K}, title = {Job tasks, potential exposures, and health risks of laborers employed in the construction industry.}, journal = {American journal of industrial medicine}, volume = {24}, number = {4}, pages = {413-425}, doi = {10.1002/ajim.4700240407}, pmid = {8250061}, issn = {0271-3586}, mesh = {Facility Design and Construction/statistics & numerical data ; Humans ; Industry/*statistics & numerical data ; Occupational Diseases/*epidemiology/mortality ; Occupational Health/*statistics & numerical data ; Risk Factors ; Task Performance and Analysis ; United States/epidemiology ; }, abstract = {Construction laborers have some of the highest death rates of any occupation in the United States. There has been very little systematic research focused exclusively on "laborers" as opposed to other workers in the construction industry. We reviewed the English language literature and various data bases describing the occupational tasks, exposures, and work-related health risks of construction laborers. The sources of information included 1) occupational mortality surveillance data collected by the states of California and Washington and the National Institute for Occupational Safety and Health (NIOSH); 2) National Occupational Exposure Survey; 3) national fatality data; 4) cancer registry data; and 5) case reports of specific causes of morbidity. While the literature reported that construction laborers have increased risk for mesothelioma, on-the-job trauma, acute lead poisoning, musculoskeletal injury, and dermatitis, the work relatedness of excess risks for all-cause mortality, cirrhosis, cerebrovascular disease, chronic obstructive pulmonary disease, ischemic heart disease, and leukemia is less clear. Furthermore, while laborers are known to be potentially exposed to asbestos, noise, and lead, and the NIOSH Job Exposure Matrix describes other potential hazardous exposures, little research has characterized other possible exposures and no research has been found that describes the exposures associated with specific job tasks. More advanced study designs are needed that include a better understanding of the job tasks and exposures to construction laborers, in order to evaluate specific exposure-disease relationships and to develop intervention programs aimed at reducing the rate of work-related diseases.}, } @article {pmid8218088, year = {1993}, author = {Sproat, CP and Brown, AE and Lindley, RP}, title = {Oral metastasis in malignant pleural mesothelioma.}, journal = {The British journal of oral & maxillofacial surgery}, volume = {31}, number = {5}, pages = {316-317}, doi = {10.1016/0266-4356(93)90069-9}, pmid = {8218088}, issn = {0266-4356}, mesh = {Asbestos/adverse effects ; Fatal Outcome ; Humans ; Male ; Mandibular Neoplasms/*secondary ; Mesothelioma/*secondary ; Middle Aged ; Pleural Neoplasms/etiology/*pathology ; }, abstract = {A case is reported of a 48-year-old man with malignant sarcomatous pleural mesothelioma, who presented with a secondary deposit in the mandibular alveolus. We believe that this is the first reported case of this nature.}, } @article {pmid8217849, year = {1993}, author = {de Klerk, NH and Musk, AW and Cookson, WO and Glancy, JJ and Hobbs, MS}, title = {Radiographic abnormalities and mortality in subjects with exposure to crocidolite.}, journal = {British journal of industrial medicine}, volume = {50}, number = {10}, pages = {902-906}, pmid = {8217849}, issn = {0007-1072}, mesh = {Asbestos, Crocidolite/*adverse effects ; Asbestosis/mortality ; Cause of Death ; Cohort Studies ; Humans ; Male ; Mesothelioma/mortality ; Neoplasms/mortality ; Occupational Diseases/diagnostic imaging/mortality ; Occupational Exposure/*adverse effects ; Pleura/*diagnostic imaging ; Pleural Diseases/*diagnostic imaging/mortality ; Radiography ; Random Allocation ; Western Australia/epidemiology ; }, abstract = {Plain chest radiographs from a one in six random sample of the workforce of the asbestos industry at Wittenoom, Western Australia between 1943 and 1966 have been classified for degree of profusion and pleural thickening by two independent observers according to the 1980 UICC-ILO Classification of Radiographs for the pneumoconioses to clarify the effect of degree of radiological abnormality on survival. A total of 1106 subjects were selected. Each subject's age, cumulative exposure to crocidolite, and time since first exposure were determined from employment records, the results of a survey of airborne concentrations of fibres > 5 mu in length conducted in 1966, and an exposure rating by an industrial hygienist and an ex-manager of the mine and mill at Wittenoom. By the end of 1986 193 subjects had died. Conditional logistic regression was used to model the relative risk of death in five separate case-control analyses in which the outcomes were deaths from: (1) all causes, (2) malignant mesothelioma, (3) lung cancer, (4) asbestosis, and (5) other causes excluding cancer and asbestosis. Up to 20 controls per case were randomly chosen from all men of the same age who were not known to have died before the date of death of the index case. After adjustment for exposure and time since first exposure, there were significant and independent effects of radiographic profusion and pleural thickening on all cause mortality. The effect of profusion was largely a result of the effect on mortality from malignant mesothelioma and asbestosis but not lung cancer. The effect of pleural thickening was greatest on mortality from other causes, mainly ischaemic heart disease. This study has shown that degree of radiographic abnormality has an independent effect on mortality from malignant mesothelioma, asbestosis, and all causes even after allowing for the effects of age, degree of exposure, and time since first exposure.}, } @article {pmid8217848, year = {1993}, author = {Yano, E and Tanaka, K and Funaki, M and Maeda, K and Matsunaga, C and Yamaoka, K}, title = {Effect of smoking on pleural thickening in asbestos workers.}, journal = {British journal of industrial medicine}, volume = {50}, number = {10}, pages = {898-901}, pmid = {8217848}, issn = {0007-1072}, mesh = {Aged ; *Asbestos ; Humans ; Male ; Middle Aged ; Occupational Diseases/*etiology/pathology ; *Occupational Exposure ; Pleura/pathology ; Pleural Diseases/*etiology/pathology ; Smoking/*adverse effects/pathology ; }, abstract = {It is well known that an interaction exists between smoking and exposure to asbestos in the occurrence of lung cancer, whereas occurrence of malignant mesothelioma has not been related to smoking. In the case of pleural thickening related to asbestos, there is a disagreement in previous studies as to the effect of smoking. This could be because the diagnosis of pleural changes has a subjective element. Taking this into account, in the present work the maximum width of the pleura was used as an index of pleural changes. Study subjects were 134 asbestos workers of a brake manufacturing company who had received medical checks in 1978 and in 1990. The maximum width of the pleura on the chest x ray films of the workers was measured by two examiners who did not know the year of examination or smoking state of the worker. A general linear model was applied to analyse the effects of smoking, the year of examination, age, and duration of exposure to asbestos. The difference between maximum widths measured in 1978 and 1990 suggested chronological progression. The increase in width during the 12 years, however, did not differ significantly between smokers and nonsmokers. This suggests that smoking does not significantly increase pleural thickening in asbestos workers.}, } @article {pmid8189372, year = {1993}, author = {Wong, O and Foliart, DE}, title = {Epidemiological factors of cancer in Louisiana.}, journal = {Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer}, volume = {12}, number = {4}, pages = {171-183}, pmid = {8189372}, issn = {0731-8898}, mesh = {Case-Control Studies ; Cohort Studies ; Diet/adverse effects ; Humans ; Louisiana/epidemiology ; Lung Neoplasms/epidemiology/mortality ; Neoplasms/*epidemiology/mortality ; Occupational Exposure/adverse effects ; Risk Factors ; Smoking/epidemiology ; Water Supply ; }, abstract = {Certain Louisiana cancer rates are higher than the national averages. This review evaluates the existing epidemiologic literature pertaining to risk factors for cancer in Louisiana. Population-based case-control studies have identified smoking as the most important contributor to lung cancer in Louisiana. Nutritional factors have been found to impart a modest increase in lung, pancreas, and stomach cancer risk. Occupational epidemiologic studies have revealed exposure to asbestos in the cement, shipbuilding, and related industries as a significant risk factor for mesothelioma and lung cancer. Sugarcane farming has been found to increase the risk of lung cancer among sugarcane farmers who smoke, and the risk of mesothelioma among sugarcane farmers in general. Occupations with exposure to microwave and radio frequency electromagnetic radiation have been associated with an increased risk of brain cancer. An increased risk of laryngeal cancer has been observed among workers exposed to sulfuric acid at a Baton Rouge isopropyl alcohol plant. Except for the laryngeal cancer finding, data from occupational cohort studies of refinery/chemical workers revealed no significant excess in cancer of all sites, cancer of the lung, or any other cancer. Relevant epidemiologic data also revealed no increased cancer risk associated with potential exposures to industrial emissions among residents in communities adjacent to petrochemical facilities.}, } @article {pmid8106851, year = {1993}, author = {Kohyama, N and Kyono, H and Yokoyama, K and Sera, Y}, title = {Evaluation of low-level asbestos exposure by transbronchial lung biopsy with analytical electron microscopy.}, journal = {Journal of electron microscopy}, volume = {42}, number = {5}, pages = {315-327}, pmid = {8106851}, issn = {0022-0744}, mesh = {Adult ; Aged ; Asbestos/*adverse effects/*analysis ; Asbestosis/diagnosis/etiology ; Biopsy ; Dust/adverse effects ; Electron Probe Microanalysis/*methods ; Environmental Monitoring ; Female ; Humans ; Lung/*chemistry/*ultrastructure ; Lung Neoplasms/diagnosis/etiology ; Male ; Mesothelioma/diagnosis/etiology ; Microscopy, Electron ; Middle Aged ; Occupational Diseases/diagnosis/etiology ; Occupational Exposure ; Pneumoconiosis/diagnosis/etiology ; }, abstract = {To improve diagnostic sensitivity for detecting low-level asbestos exposure (AEx) in patients, a new method was developed using an analytical transmission electron microscope (ATEM) for specimens of transbronchial lung biopsy (TBLB). The TBLB specimens from 28 patients were examined and the results were: 1) In cases with long-term AEx, the present method detected a large amount of asbestos fibers (AF) as well as asbestos bodies (AB) showing a good agreement with the results of light microscope (LM) which detected definite amounts of ferruginous bodies (FB). 2) In cases with short-term or suspected AEx, the LM failed to detect FB in some cases, but an appreciable amount of AF was detected using the present method, and AEx was disclosed through a second close interview. 3) Neither AB nor AF were detected in most of the cases without any dust exposure. Although small amounts of chrysotile fibers were observed in some cases, this might simply reflect the exposure level of urban dwellers. These results show that the ATEM applied to the TBLB specimens promises to confirm low-level AEx in such small specimens even if the patients were unaware of their past AEx.}, } @article {pmid8375935, year = {1993}, author = {Zeng, L and Buard, A and Monnet, I and Boutin, C and Fleury, J and Saint-Etienne, L and Brochard, P and Bignon, J and Jaurand, MC}, title = {In vitro effects of recombinant human interferon gamma on human mesothelioma cell lines.}, journal = {International journal of cancer}, volume = {55}, number = {3}, pages = {515-520}, doi = {10.1002/ijc.2910550331}, pmid = {8375935}, issn = {0020-7136}, mesh = {Aged ; Aged, 80 and over ; Animals ; Cell Division/drug effects ; Drug Screening Assays, Antitumor ; Female ; Humans ; Interferon-gamma/*pharmacology ; Male ; Mesothelioma/*pathology/therapy ; Mice ; Mice, Nude ; Middle Aged ; Pleural Neoplasms/*pathology/therapy ; Recombinant Proteins ; Tumor Cells, Cultured ; }, abstract = {Malignant mesothelioma is a tumor arising from serous surfaces and often related to asbestos exposure. Malignant mesothelioma is resistant to various forms of therapy. Radiotherapy, surgery or chemotherapy only slightly improve prognosis. IFN-gamma produces complete or partial responses in stage-I patients with malignant mesothelioma. The in vitro biological effect of IFN-gamma on malignant mesothelioma cells remains poorly elucidated. In the present study, 32 well-characterized human mesothelioma cell lines (HMCL) were treated with r-hu IFN-gamma at 4 doses and cell growth was determined by a colorimetric method (MTT assay). Among the 32 HMCLs tested, II exhibited significant cell-growth inhibition; 16 were insensitive to r-hu IFN-gamma, and 5 were slightly inhibited. The sensitive cell lines were strongly inhibited by r-hu IFN-gamma. Our results show that HMCL exhibit a large range of responses to r-hu IFN-gamma, some of which can be compared with those obtained in vivo in humans.}, } @article {pmid8398870, year = {1993}, author = {Magnani, C and Terracini, B and Ivaldi, C and Botta, M and Budel, P and Mancini, A and Zanetti, R}, title = {A cohort study on mortality among wives of workers in the asbestos cement industry in Casale Monferrato, Italy.}, journal = {British journal of industrial medicine}, volume = {50}, number = {9}, pages = {779-784}, pmid = {8398870}, issn = {0007-1072}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Cause of Death ; Cohort Studies ; Environmental Exposure/*adverse effects ; *Family ; Female ; Follow-Up Studies ; Humans ; Italy/epidemiology ; Lung Neoplasms/etiology ; Male ; Mesothelioma/etiology ; Middle Aged ; Neoplasms/*mortality ; Occupational Exposure ; Pleural Neoplasms/etiology ; Retrospective Studies ; }, abstract = {The study investigates mortality from cancer and other diseases in a cohort of wives of asbestos cement workers in Casale Monferrato (northwest Italy). After the exclusion of women with an occupational record in the asbestos cement industry, the cohort comprised 1964 women. Their domestic exposure was estimated according to their husbands' periods of employment in the plant: 1740 had a period of domestic exposure whereas the remaining 224 married an asbestos cement worker only after he definitely stopped his activity in the asbestos cement plant; these have, therefore, been considered as unexposed. The cohort of wives was constructed entirely through official records in the town offices and is both exhaustive and unaffected by recall bias. At the end of follow up (1988) 1669 women were alive, 270 were dead and 25 (1.2%) were untraced. Main mortality analyses were only up to age 79 to reduce the misclassification of causes of death. Expected mortality was based on local rates. Mortality analyses were limited to the period 1965-88 due to the availability of local rates: in that period 210 deaths occurred among women with domestic exposure v 229.1 expected. There were four deaths from pleural tumours (one diagnosed as mesothelioma at necropsis) and six from lung cancer v. 0.5 and 4.0 expected respectively. Two further cases of mesothelioma were diagnosed by histological examination after the end of follow up. None of the three wives with histologically diagnosed mesothelioma had been engaged in industrial activities. Corresponding information for the other three cases could not be traced.}, } @article {pmid8398869, year = {1993}, author = {Newhouse, ML and Thompson, H}, title = {Mesothelioma of pleura and peritoneum following exposure to asbestos in the London area. 1965.}, journal = {British journal of industrial medicine}, volume = {50}, number = {9}, pages = {769-778}, pmid = {8398869}, issn = {0007-1072}, mesh = {Asbestos/*adverse effects ; History, 20th Century ; Humans ; Mesothelioma/*history ; Occupational Diseases/*history ; Peritoneal Neoplasms/*history ; Pleural Neoplasms/*history ; }, } @article {pmid8394641, year = {1993}, author = {Sahin, AA and Cöplü, L and Selçuk, ZT and Eryilmaz, M and Emri, S and Akhan, O and Bariş, YI}, title = {Malignant pleural mesothelioma caused by environmental exposure to asbestos or erionite in rural Turkey: CT findings in 84 patients.}, journal = {AJR. American journal of roentgenology}, volume = {161}, number = {3}, pages = {533-537}, doi = {10.2214/ajr.161.3.8394641}, pmid = {8394641}, issn = {0361-803X}, mesh = {Adult ; Aged ; Aluminum Silicates/*adverse effects ; Asbestos/*adverse effects ; *Asbestos, Amphibole ; Environmental Exposure ; Female ; Humans ; Male ; Mesothelioma/*diagnostic imaging/*etiology ; Middle Aged ; Pleura/diagnostic imaging ; Pleural Neoplasms/*diagnostic imaging/*etiology ; Radiography, Thoracic ; Retrospective Studies ; Silicic Acid/*adverse effects ; *Tomography, X-Ray Computed ; Turkey ; Zeolites ; }, abstract = {OBJECTIVE: Malignant pleural mesothelioma in rural Turkey frequently results from environmental exposure to tremolite asbestos or fibrous zeolite (erionite). The aim of this study was to determine the CT features of malignant pleural mesothelioma in patients exposed to asbestos or erionite.

MATERIALS AND METHODS: The CT scans of 84 patients with proved malignant pleural mesothelioma were retrospectively evaluated. Twenty patients (24%) had been exposed to erionite and 64 patients (76%) had been exposed to asbestos. The CT scans were interpreted by seven observers who did not know the clinical or pathologic findings.

RESULTS: CT scans showed either unilateral pleural thickening or pleural nodules/masses in all patients. Pleural nodules were present in 25 patients (30%) and pleural masses in 44 patients (52%). Pleural effusion was found in 61 patients (73%), mediastinal pleural involvement in 78 (93%), pleural calcifications in 52 (62%), involvement of the interlobar fissures in 64 (76%), and volume contraction in 61 (73%). Reduced size of the hemithorax was significantly correlated with chest wall involvement. On the basis of CT findings, the preassigned staging was changed in 21 patients (25%), including 44% of the patients with disease that had been classified as stage I. CT findings were not significantly different between the patients exposed to erionite and those exposed to asbestos.

CONCLUSION: The most common CT findings in cases of malignant pleural mesothelioma were unilateral pleural thickening or pleural nodules/masses with or without effusion. CT provided valuable information on the extent of the disease, which was important for staging. Although the CT features are not pathognomonic, they provide valuable clues to the diagnosis in patients who have been exposed to mineral fibers.}, } @article {pmid8377505, year = {1993}, author = {Qua, JC and Rao, UN and Takita, H}, title = {Malignant pleural mesothelioma: a clinicopathological study.}, journal = {Journal of surgical oncology}, volume = {54}, number = {1}, pages = {47-50}, doi = {10.1002/jso.2930540113}, pmid = {8377505}, issn = {0022-4790}, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Combined Modality Therapy ; Female ; Humans ; Incidence ; Lymphatic Metastasis ; Male ; Mesothelioma/diagnosis/*epidemiology/mortality/therapy ; Middle Aged ; New York/epidemiology ; Pleural Neoplasms/diagnosis/*epidemiology/mortality/therapy ; Retrospective Studies ; Sex Factors ; }, abstract = {In this paper the results of a retrospective review of 58 patients with malignant pleural mesothelioma treated at our Institute are reported. There were 50 males and 8 females; the mean age was 56.3 years (range: 13-77). History of asbestos exposure was ascertained in 25 patients (43%). The most common finding in chest X-ray was pleural effusion which was seen in 47/58 patients on presentation. The cytological examination of pleural effusion was most of the time nondiagnostic. Pleural biopsy was needed for the correct diagnosis. Pathologically, 26 patients (44.8%) had epithelial type, 24 patients (41.4%) had mixed type, and 8 patients (13.8%) had fibrous or sarcomatous type of pleural mesothelioma. Most of the patients on presentation had Stage I disease by Butchart's classification. The overall survival time ranged from 1 month to as long as 17 years with a median of 12.5 months. The mean survival of patients who received nonsurgical therapies was 7-13.4 months. Thirteen patients were treated surgically: three patients survived over 5 years, but the median survival was 15 months. Six patients received no treatment, and the median survival was seven months.}, } @article {pmid8275990, year = {1993}, author = {Sekhon, HS and Keeling, B and Churg, A}, title = {Rat pleural mesothelial cells show damage after exposure to external but not internal cigarette smoke.}, journal = {Environmental health perspectives}, volume = {101}, number = {4}, pages = {326-330}, pmid = {8275990}, issn = {0091-6765}, mesh = {Animals ; Epithelium/pathology ; Female ; Hydrogen Peroxide/adverse effects ; Pleura/metabolism/*pathology ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species/*adverse effects ; Smoking/*adverse effects ; Tobacco Smoke Pollution/*adverse effects ; Trypan Blue/metabolism ; }, abstract = {The combination of cigarette smoke and high-level occupational asbestos exposure produces a synergistic increase in the incidence of lung cancer; however, smoking does not affect the incidence of mesothelioma. Here we present the results of tests of two theories that have been proposed to explain this phenomenon; namely, that pleural mesothelial cells are resistant to cigarette smoke-induced damage and that the pleural connective tissue acts as a barrier that prevents smoke from reaching the mesothelial cells. To test these hypotheses, excised whole rat lung preparations were exposed to either internal (intratracheal) or external (pleural surface) smoke. For comparison, additional excised lung preparations were exposed to solutions of hydrogen peroxide either externally or intratracheally. Mesothelial cells exposed to external smoke showed widespread, dose-dependent uptake of Trypan blue. Mesothelial cells did not take up Trypan blue after exposure to internal smoke. Bronchial epithelial cells exposed to internal smoke did show uptake, but to a lesser degree than externally exposed mesothelial cells. Examination by scanning and transmission electron microscopy showed that internal smoke did not affect mesothelial cell ultrastructure, whereas external smoke produced obvious mesothelial cell damage and mesothelial cell detachment. Catalase and deferoxamine, scavengers of active oxygen species, provided protection against smoke-induced mesothelial cell injury, but inactivated catalase did not. External hydrogen peroxide produced a very similar, dose-dependent pattern of Trypan blue uptake and ultrastructural changes. Intratracheal hydrogen peroxide also damaged mesothelial cells, but the extent of damage was always less than with comparable concentrations of external hydrogen peroxide.(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid8114650, year = {1993}, author = {Paoletti, L and Falchi, M and Batisti, D and Zappa, M and Chellini, E and Biancalani, M}, title = {Characterization of asbestos fibers in pleural tissue from 21 cases of mesothelioma.}, journal = {La Medicina del lavoro}, volume = {84}, number = {5}, pages = {373-378}, pmid = {8114650}, issn = {0025-7818}, mesh = {Adult ; Aged ; Asbestos/*analysis ; Female ; Humans ; Male ; Mesothelioma/*chemistry ; Middle Aged ; *Occupational Diseases ; *Occupational Exposure ; Pleural Neoplasms/*chemistry ; }, abstract = {Pleural biopsies from 21 patients with pleural mesothelioma and different asbestos exposure were analyzed by means of analytical electron microscopy with the aim of investigating the presence, quantity, types and sizes of asbestos fibers in pleural tissue. The majority of fibers found consisted of ultrathin (< 0.3 micron) and short (< 5 microns) fibers regardless of asbestos types and subject exposure. Concentrations appeared to be poorly related to the estimated exposure level. Fiber dimensions appeared to be the most important characteristic which determined their translocation in the pleural region.}, } @article {pmid8398854, year = {1993}, author = {Mossman, BT}, title = {Mechanisms of asbestos carcinogenesis and toxicity: the amphibole hypothesis revisited.}, journal = {British journal of industrial medicine}, volume = {50}, number = {8}, pages = {673-676}, pmid = {8398854}, issn = {0007-1072}, support = {HL 14212/HL/NHLBI NIH HHS/United States ; HL 39469/HL/NHLBI NIH HHS/United States ; }, mesh = {Asbestos, Amphibole/*adverse effects ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Occupational Exposure/*adverse effects ; }, } @article {pmid8394779, year = {1993}, author = {Linnainmaa, K and Pelin, K and Vanhala, E and Tuomi, T and Piccoli, C and Fitzgerald, DJ and Yamasaki, H}, title = {Gap junctional intercellular communication of primary and asbestos-associated malignant human mesothelial cells.}, journal = {Carcinogenesis}, volume = {14}, number = {8}, pages = {1597-1602}, doi = {10.1093/carcin/14.8.1597}, pmid = {8394779}, issn = {0143-3334}, support = {R01 CA40-534/CA/NCI NIH HHS/United States ; }, mesh = {Asbestos/*adverse effects ; Cell Communication/*drug effects/*physiology ; Cells, Cultured ; Connexins ; Epithelial Cells ; Epithelium/drug effects/physiology ; Gene Expression/drug effects/genetics ; Humans ; Intercellular Junctions/*drug effects/*physiology ; Membrane Proteins/genetics ; Mesothelioma/etiology/genetics/*pathology ; Pleural Neoplasms/etiology/genetics/*pathology ; Tetradecanoylphorbol Acetate/toxicity ; Tumor Cells, Cultured ; }, abstract = {We examined gap junctional intercellular communication (GJIC) of primary human mesothelial cells and cell lines of asbestos-associated human pleural mesotheliomas, and the effect of asbestos and other mineral fibres on these cells. In homologous cultures, the GJIC capacity of six out of seven tumour cell lines was markedly less than for primary mesothelial cells. This defect in GJIC appeared not to be at the expression level of mRNA and protein of the gene encoding the 43 kDa gap junction protein. In heterologous cocultures of tumour cells and primary mesothelial cells, however, 80-90% of the tumour cell/normal cell contacts were functional. Exposure of primary mesothelial cells to TPA, a phorbol ester tumour promoter, resulted in marked inhibition of GJIC, being an action common to numerous tumour promoters. Such an effect though was not observed with the carcinogenic mesothelioma-inducing mineral fibres chrysotile and amosite, neither with glass wool. These results suggest that a permanent defect in GJIC capacity is a common feature of human mesothelioma cells, but how mineral fibres are involved in the process of mesotheliomagenesis is still unclear.}, } @article {pmid8393329, year = {1993}, author = {Yegles, M and Saint-Etienne, L and Renier, A and Janson, X and Jaurand, MC}, title = {Induction of metaphase and anaphase/telophase abnormalities by asbestos fibers in rat pleural mesothelial cells in vitro.}, journal = {American journal of respiratory cell and molecular biology}, volume = {9}, number = {2}, pages = {186-191}, doi = {10.1165/ajrcmb/9.2.186}, pmid = {8393329}, issn = {1044-1549}, mesh = {Anaphase/drug effects ; Aneuploidy ; Animals ; Asbestos/*toxicity ; Asbestos, Crocidolite ; Cell Cycle/*drug effects ; Cells, Cultured ; Chromosome Aberrations ; Epithelial Cells ; Epithelium/drug effects ; Metaphase/drug effects ; Mutagens/*toxicity ; Pleura/cytology/*drug effects ; Rats ; Telophase/drug effects ; Titanium/toxicity ; }, abstract = {The cytogenetic effects of asbestos fibers on rat pleural mesothelial cells were studied in vitro. Crocidolite UICC significantly enhanced aneuploidy and produced few structural chromosome aberrations, whereas anatase, an isomorphic particle, induced no numerical or structural changes. Mitomycin C (300 nM) produced a tenfold increase in abnormal anaphases compared with controls. Asbestos produced anaphase/telophase abnormalities in a concentration-dependent manner. The majority of the abnormalities involved lagging chromosomes. Crocidolite UICC induced abnormalities at a dose of 7.0 micrograms/cm2, whereas Canadian chrysotile did so at 1.0 to 2.0 micrograms/cm2. When the response was assessed by the number of long and thin fibers per cm2 (length > 8 microns; diameter < or = 0.25 microns), crocidolite UICC produced more abnormalities than Canadian chrysotile at all concentrations. On a per-weight basis, these findings differ from those obtained after intrapleural inoculation, as crocidolite induced more mesotheliomas than chrysotile; however, on a per-fiber basis, the in vitro and in vivo effects were similar. These results show that anaphase/telophase analysis is sensitive and complementary to metaphase analysis, and suggest that asbestos might produce cell transformation by inducing chromosome missegregation and aneuploidy.}, } @article {pmid8372302, year = {1993}, author = {Nassiopoulos, K and Rostan, O and Petropoulos, P}, title = {[Pleural mesothelioma. Review of 3 cases and role of thoracoscopy].}, journal = {Revue medicale de la Suisse romande}, volume = {113}, number = {8}, pages = {603-606}, pmid = {8372302}, issn = {0035-3655}, mesh = {Biopsy ; Humans ; Male ; Mesothelioma/diagnosis/*pathology/surgery ; Middle Aged ; Pleural Neoplasms/diagnosis/*pathology/surgery ; *Thoracoscopy ; }, abstract = {Pleural mesotheliomas are uncommon tumors that can be classified as localized fibrous or diffuse malignant. The frequency in the general population is low and, as it concern the diffuse malignant type, exposure to asbestos, significantly increases the incidence. The most common symptoms are chest pain, short of breath and cough and the roentgenological findings are solitary or multiple pleural nodular lesions. The fibrous type can be excised and recurrence rarely occurs, but the malignant type does not respond either to chemotherapy or to radiotherapy and surgical measures offer only palliation. Thoracoscopy is a possibility of surgical excision in a case of localized mesothelioma and in case of diffuse type it contributes to the diagnostic yield, the open surgical procedures to be considered only in functionally operable patients.}, } @article {pmid8213850, year = {1993}, author = {Dodson, RF and O'Sullivan, M and Corn, C}, title = {Technique dependent variations in asbestos burden as illustrated in a case of nonoccupational exposed mesothelioma.}, journal = {American journal of industrial medicine}, volume = {24}, number = {2}, pages = {235-240}, doi = {10.1002/ajim.4700240210}, pmid = {8213850}, issn = {0271-3586}, mesh = {Asbestos/*adverse effects ; Body Burden ; Humans ; Male ; Mesothelioma/*etiology ; Middle Aged ; Peritoneal Neoplasms/*etiology ; }, } @article {pmid8213843, year = {1993}, author = {Bianchi, C and Brollo, A and Ramani, L and Zuch, C}, title = {Asbestos-related mesothelioma in Monfalcone, Italy.}, journal = {American journal of industrial medicine}, volume = {24}, number = {2}, pages = {149-160}, doi = {10.1002/ajim.4700240203}, pmid = {8213843}, issn = {0271-3586}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Female ; Humans ; Italy/epidemiology ; Male ; Mesothelioma/epidemiology/*etiology ; Middle Aged ; Occupational Diseases/epidemiology/*etiology ; Peritoneal Neoplasms/epidemiology/*etiology ; Pleural Neoplasms/epidemiology/*etiology ; Prospective Studies ; Ships ; }, abstract = {The Monfalcone area, in northeastern Italy, is a small industrial territory (population about 60,000), with a large shipyard. Between October 1979 and April 1992, ninety-two malignant mesotheliomas were diagnosed at the Monfalcone Hospital. The series included 84 men and 8 women, aged 42 to 89 years (median age 68 years). There were 89 pleural and 3 peritoneal tumors. Seventy patients (69 men and 1 woman) had worked in the shipyards; six were seamen, and four insulators. Five men had been exposed to asbestos in various industries; six women had histories of domestic exposure, and one woman had a history of possible environmental exposure. The latency periods (intervals between first exposure to asbestos and diagnosis of the tumor) ranged from 20 to 65 years (median 52 years). Latency periods among insulators were significantly lower than among shipyard workers, as well as lower than among the other categories (p < 0.01). Lung asbestos bodies were isolated after chemical digestion in 73 cases at necropsy, and in two cases at surgery. In necropsy cases, asbestos body burdens ranged between 100 and 10,000,000 bodies per gram of dried tissue (median 11,000). Pleural plaques were observed at necropsy in 62 out of 73 cases, and in two cases at surgery. In the time period we considered, the annual incidence rates for pleural mesothelioma were very high among male Monfalcone residents, being 189 per 100,000 among people aged 75 years or more. On the basis of occupational data and of objective signs (lung asbestos bodies, pleural plaques), all the cases of the present series but one (that with possible environmental exposure) were considered as asbestos-related. The role of co-factors in the development of asbestos-related mesothelioma is suggested.}, } @article {pmid8369700, year = {1993}, author = {Mayall, FG}, title = {The hazards of asbestos. Inaccurate diagnoses distort results.}, journal = {BMJ (Clinical research ed.)}, volume = {307}, number = {6898}, pages = {258-259}, pmid = {8369700}, issn = {0959-8138}, mesh = {Asbestos/*adverse effects ; Diagnostic Errors ; Humans ; Lung Neoplasms/*diagnosis/pathology ; Mesothelioma/diagnosis/pathology ; Occupational Diseases/*diagnosis ; }, } @article {pmid8319172, year = {1993}, author = {De Pangher Manzini, V and Brollo, A and Franceschi, S and De Matthaeis, M and Talamini, R and Bianchi, C}, title = {Prognostic factors of malignant mesothelioma of the pleura.}, journal = {Cancer}, volume = {72}, number = {2}, pages = {410-417}, doi = {10.1002/1097-0142(19930715)72:2<410::aid-cncr2820720216>3.0.co;2-g}, pmid = {8319172}, issn = {0008-543X}, mesh = {Adult ; Aged ; Female ; Humans ; Italy ; Male ; Mesothelioma/*mortality ; Middle Aged ; Multivariate Analysis ; Pleural Neoplasms/*mortality ; Prognosis ; Time Factors ; }, abstract = {BACKGROUND: Pleural mesothelioma is a rare condition with a poor prognosis. The area of Monfalcone, North East Italy, provided a unique opportunity to study the disease because of its past heavy exposure to asbestos in local harbors and shipyards and its high necropsy rates.

METHODS: The effects of various patient and tumor characteristics on survival were evaluated in 80 patients (73 males and 7 females; median age, 69) of histologically or cytologically confirmed malignant mesothelioma of the pleura. These patients were examined between October 1979 and October 1991 at the General Hospital of Monfalcone in the Friuli-Venezia Giulia region. Substantial exposures to asbestos were identified in 79 patients.

RESULTS: Median survival rate was 13 months (range, 2-44 months), and overall 2- and 5-year survival rates were 23% and 0%, respectively. The factors that exerted a significant favorable influence on survival were as follows: (1) age younger than 65; (2) performance status less than or equal to one; (3) lack of less than or equal to 10% weight loss at any time; (4) Stages I and II; (5) epithelial or mixed histologic type; and (6) presence of pleural fluid with mesothelial cells but without neoplastic cells. When these factors were introduced in a Cox proportional hazard model, age, stage, and histologic type were the only independent prognostic factors. The increased hazards for patients, ages 65-74 (as compared to < 65), and for patients with sarcomatous histologic type (as compared to epithelial type) were 2.6 (95% confidence interval [CI], 1.2-5.7) and 4.5 (95% CI, 1.6-12.8).

CONCLUSIONS: Survival rate in 24 untreated patients (median, 10 months) and 56 patients variously treated (median, 15 months) did not differ significantly. The availability of large portions of tumor specimens for histologic examinations in 77 of 80 patients, chiefly from high necropsy rate, strengthens the value of the present analysis of prognostic factors.}, } @article {pmid8415588, year = {1993}, author = {Cagle, PT and Wessels, R and Greenberg, SD}, title = {Concurrent mesothelioma and adenocarcinoma of the lung in a patient with asbestosis.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {6}, number = {4}, pages = {438-441}, pmid = {8415588}, issn = {0893-3952}, mesh = {Adenocarcinoma/chemistry/etiology/*pathology ; Asbestosis/*complications ; Humans ; Lung Neoplasms/chemistry/etiology/*pathology ; Male ; Mesothelioma/chemistry/etiology/*pathology ; Middle Aged ; Neoplasms, Multiple Primary/chemistry/etiology/*pathology ; }, abstract = {We report the apparently unique simultaneous development of a mesothelioma and an adenocarcinoma of the lung in a patient with asbestosis. Pathologists should be aware that very rarely these two malignancies may occur concurrently, an event with potential prognostic, therapeutic, and medical-legal implications for the patient and his family. Although occupational asbestos exposure is well recognized as a risk factor in the development of both mesothelioma and lung carcinoma, this case report emphasizes the rarity of the synchronous occurrence of these tumors in asbestos exposed individuals suggesting that the mechanism by which asbestos fibers induce lung carcinoma is different from that by which they induce mesothelioma.}, } @article {pmid8391235, year = {1993}, author = {Churg, A and Wright, JL and Vedal, S}, title = {Fiber burden and patterns of asbestos-related disease in chrysotile miners and millers.}, journal = {The American review of respiratory disease}, volume = {148}, number = {1}, pages = {25-31}, doi = {10.1164/ajrccm/148.1.25}, pmid = {8391235}, issn = {0003-0805}, mesh = {Aged ; Asbestos/*adverse effects ; *Asbestos, Amphibole ; Asbestos, Serpentine ; Asbestosis/epidemiology/etiology/*pathology ; Humans ; Lung/ultrastructure ; Lung Neoplasms/epidemiology/etiology/ultrastructure ; Mesothelioma/epidemiology/etiology/ultrastructure ; Microscopy, Electron ; Middle Aged ; *Mining/statistics & numerical data ; Particle Size ; Pleural Diseases/epidemiology/etiology/pathology ; Pulmonary Fibrosis/epidemiology/etiology/pathology ; Quebec/epidemiology ; Regression Analysis ; Silicic Acid/adverse effects ; }, abstract = {To examine how fiber type, fiber concentration, and fiber size correlate with the presence of asbestos-related disease in workers with heavy chrysotile exposure, we used analytic electron microscopy to determine the fiber content of the lungs of 94 long-term chrysotile miners and millers from the region of Thetford Mines, Quebec. Mesothelioma, airway fibrosis, and asbestosis were strongly associated with a high tremolite fiber concentration, whereas pleural plaques and carcinoma of the lung showed no relationship to tremolite burden. Similar patterns were seen for chrysotile concentration, but further analysis suggested that the apparent effect of chrysotile probably was due to the high correlation (r = 0.70) between chrysotile and tremolite concentration rather than to an independent effect of chrysotile. Increased tremolite-chrysotile ratio was marginally associated with the presence of pleural plaques but not with any other disease. Very high correlations (r > 0.90) between the concentrations of fibers longer or shorter than 8 microns prevented assessment of the effects of long compared with short fibers. Pleural plaques were very strongly associated with higher mean tremolite fiber aspect ratios, but no differences in mean fiber size (length, width, aspect ratio, surface area, and mass) were seen for any other disease. Total fiber size measures (total fiber length/g and others) showed differences similar to fiber concentration for mesothelioma, airways fibrosis, and asbestosis, but no one measure was clearly better than another or better than fiber concentration. We conclude that, in this population of heavily exposed chrysotile miners and millers, the presence of airways fibrosis and asbestosis and, probably, mesothelioma reflects high tremolite burden.(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid8376182, year = {1993}, author = {Deitmer, T and Borsch-Galetke, E}, title = {[Nose and paranasal sinus malignancies with reference to occupational medicine aspects. A case study].}, journal = {HNO}, volume = {41}, number = {7}, pages = {352-355}, pmid = {8376182}, issn = {0017-6192}, mesh = {Asbestos/*adverse effects ; Asbestosis/etiology ; Dust/adverse effects ; Female ; Humans ; Male ; Nose Neoplasms/*etiology ; Occupational Diseases/*etiology ; Occupational Exposure/*adverse effects ; Paranasal Sinus Neoplasms/*etiology ; Risk Factors ; Wood ; }, abstract = {Asbestos is a well known inhalant cancerogenic substance, causing not only mesothelioma but also cancer of the respiratory mucosa of the bronchi. Exposure can also cause non-malignant alterations of the pleura or lung, which can be assessed radiologically. Since asbestos can also induce malignant tumors of the nose and sinuses, we identified 50 patients from the files of the ENT Department Münster and tried to complete questionnaires concerning occupation and occupational hazards using informations from insurance companies as well as at least one chest x-ray. This material could be obtained in 19 patients. Nine of the 19 patients had x-ray findings that could be associated with asbestos exposure, but in none of these 9 cases was massive occupational exposure to asbestos probable. In only two of the nine cases was definite occupational exposure to asbestos not able to be excluded. A control group was not established, since statistical calculations of significance would have been problematic in a number of the 19 patients even if a control group did exist. From the questionnaires we have found an unexpected incidence of dusty workplaces (as seen with textile workers, wood-dust workers, cement workers, quarrymen and millers). A correlation between various types of sinonasal tumors and asbestos exposure could not be made.}, } @article {pmid8364782, year = {1993}, author = {Pan, ST and Ho, WL and Yang, MD}, title = {Malignant peritoneal mesothelioma: a case report.}, journal = {Zhonghua yi xue za zhi = Chinese medical journal; Free China ed}, volume = {52}, number = {1}, pages = {53-57}, pmid = {8364782}, issn = {0578-1337}, mesh = {Carcinoembryonic Antigen/analysis ; Humans ; Male ; Membrane Glycoproteins/analysis ; Mesothelioma/*pathology/therapy/ultrastructure ; Microscopy, Electron ; Middle Aged ; Mucin-1 ; Peritoneal Neoplasms/*pathology/therapy/ultrastructure ; }, abstract = {Malignant peritoneal mesothelioma is a rare disease, not previously reported in Taiwan. The reported case concerns a 64-year-old veteran who had suffered from abdominal pain and distension for several days. After exploratory laparotomy, segmental resection of the small intestine, excised a mesenteric mass. A characteristic biphasic pattern resulting from the admixture of gland-like area and a sarcomatous stroma presented in the histologic section. A series of histochemical, immunohistochemical and ultrastructural studies proved this to be a malignant peritoneal mesothelioma. The patient died after a course of post-operative chemotherapy. History of asbestos exposure, with which the tumor is usually intimately associated, could not be traced with certainty. Poor prognosis is the rule of the disease; almost all patients die within two years of diagnosis. An effective therapeutic modality is still unavailable. Here the clinical and pathologic characteristics of the tumor are described, with a brief review and discussion of the pathogenesis as well as the obscured therapeutic problem.}, } @article {pmid8120568, year = {1993}, author = {Wroński, M and Burt, M}, title = {Cerebral metastases in pleural mesothelioma: case report and review of the literature.}, journal = {Journal of neuro-oncology}, volume = {17}, number = {1}, pages = {21-26}, pmid = {8120568}, issn = {0167-594X}, mesh = {Brain Neoplasms/*secondary ; Female ; Humans ; Mesothelioma/*secondary ; Middle Aged ; Pleural Neoplasms/*pathology ; }, abstract = {A case of malignant mesothelioma metastatic to the brain is described. A 52-year old woman, with no known exposure to asbestos, presented with a biphasic mesothelioma of the left parietal pleura. Following resection, the thorax was irradiated with 4000 cGy, and all symptoms subsided. Three months later, a left temporal lobe tumor was diagnosed and subsequently resected. Despite neurological improvement, she died 10 days post-operatively from constrictive pericardial disease. The authors have reviewed the 54 reported cases of brain metastases from mesothelioma and have noted that the histologic appearance of brain metastases from mesothelioma may be similar to glioblastoma multiforme. Because brain metastasis from mesothelioma is rare, procedures to clarify the nature of the tumor should be performed.}, } @article {pmid8390408, year = {1993}, author = {Hansen, J and de Klerk, NH and Eccles, JL and Musk, AW and Hobbs, MS}, title = {Malignant mesothelioma after environmental exposure to blue asbestos.}, journal = {International journal of cancer}, volume = {54}, number = {4}, pages = {578-581}, doi = {10.1002/ijc.2910540410}, pmid = {8390408}, issn = {0020-7136}, mesh = {Adolescent ; Adult ; Aged ; Asbestos/*adverse effects ; Asbestos, Crocidolite ; Child ; Child, Preschool ; Demography ; Environmental Exposure/*adverse effects ; Family ; Female ; Humans ; Longitudinal Studies ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupations ; Retrospective Studies ; Western Australia/epidemiology ; }, abstract = {To determine the magnitude of the population at risk from non-occupational exposure to crocidolite at Wittenoom, Western Australia (WA), a cohort of 4,890 residents who never worked for the mining company Australian Blue Asbestos (ABA) has been assembled from all 18,553 available records: the local school register, hospital attendances, the WA electoral roll, birth certificates, workers who answered a mailed questionnaire in 1979, participants in a cancer-prevention programme using vitamin-A dietary supplements, and other sources. The majority of subjects were relatives and friends of ABA employees, and nearly half the cohort were either born at Wittenoom or first went there as children under 10 years of age. As most residents were at Wittenoom when the mine and mill were in operation during the period 1943 to 1966, 82% were first exposed to crocidolite 20 or more years ago. The proportion of other workers (i.e., not employed by ABA) and their families increased once the mining operations ceased. To date, 24 cases of mesothelioma have been reported in this cohort: 9 males and 15 females. Time from first exposure to diagnosis ranged from 23 to 44 years and residence in Wittenoom ranged from 6 weeks to 11 years.}, } @article {pmid7686399, year = {1993}, author = {Lee, MM and Green, FH and Demetrick, DJ and Jiang X, X and Schürch, S}, title = {A study of surface property changes in rat mesothelial cells induced by asbestos using aqueous two-phase polymer solutions.}, journal = {Biochimica et biophysica acta}, volume = {1181}, number = {3}, pages = {223-232}, doi = {10.1016/0925-4439(93)90025-v}, pmid = {7686399}, issn = {0006-3002}, mesh = {Animals ; Asbestos/administration & dosage/*toxicity ; Cell Adhesion ; Cell Transformation, Neoplastic/chemistry/*ultrastructure ; Dextrans ; Epithelium/chemistry/ultrastructure ; Male ; Mesothelioma/chemistry/*etiology/ultrastructure ; Microscopy, Electron, Scanning ; Peritoneal Neoplasms/chemistry/*etiology/ultrastructure ; Polyethylene Glycols ; Rats ; Rats, Inbred F344 ; Surface Properties ; Thermodynamics ; Tumor Cells, Cultured ; }, abstract = {Intraperitoneal (i.p.) injection of crocidolite asbestos was used to induce mesotheliomas in rats. The morphological changes of the mesothelial cells were studied by light and electron microscopy and by cytologic examination of peritoneal washings. After injection, the asbestos fibres stimulated an acute inflammatory response and were rapidly phagocytosed by the mesothelial cells and incorporated into the submesothelial tissues. At 7 days, the normal microvillous surface of the mesothelium was replaced with a syncytium of proliferating mesothelial cells showing extensive loss of microvilli. Nine months or so later, multifocal mesothelial tumours arose within the peritoneal cavity. The surface thermodynamic properties of normal, asbestos-stimulated mesothelial cells and of mesothelial tumour cells in culture were studied using an aqueous two-phase system containing 4% Dextran T-2000 and 4% poly (ethylene glycol) (PEG) w/w. After asbestos stimulation, there was a significant (P < 0.01) increase in contact angle between the dextran-rich phase and the mesothelial cell surface. These changes were even greater for the mesothelial tumours. The results indicate that the work of adhesion for asbestos-stimulated mesothelial cells and mesothelial tumours is lower than in normal tissue. These findings may be relevant to the process of tumour spread in the serosal cavities and to the development of distant metastases.}, } @article {pmid8518676, year = {1993}, author = {De Vos Irvine, H and Lamont, DW and Hole, DJ and Gillis, CR}, title = {Asbestos and lung cancer in Glasgow and the west of Scotland.}, journal = {BMJ (Clinical research ed.)}, volume = {306}, number = {6891}, pages = {1503-1506}, pmid = {8518676}, issn = {0959-8138}, mesh = {Asbestos/*adverse effects ; Humans ; Incidence ; Lung Neoplasms/epidemiology/*etiology ; Male ; Mesothelioma/epidemiology ; Occupational Diseases/*etiology ; Occupational Exposure ; Risk Factors ; Scotland/epidemiology ; }, abstract = {OBJECTIVE: To quantify the relation between lung cancer and exposure to asbestos in men in west Scotland and to estimate the proportion of lung cancer which may be attributed to exposure to asbestos.

DESIGN: An ecological correlation study of the incidence of lung cancer in men and past asbestos exposure. The unit of analysis was the postcode sector. Correction was made for past cigarette smoking, air pollution, and deprivation.

SETTING: The region covered by the west of Scotland cancer registry, containing 2.72 million people and including Glasgow and the lower reaches of the River Clyde, where shipbuilding was once a major industry.

SUBJECTS: All men diagnosed with lung cancer between 1975 and 1984 whose residence at the time of registration was within the west of Scotland.

MAIN OUTCOME MEASURE: The population attributable risk for asbestos related lung cancer.

RESULTS: An estimated 5.7% (95% confidence interval 2.3 to 9.1%) of all lung cancers in men registered in the west of Scotland during the period 1975-84 were asbestos related, amounting to 1081 cases.

CONCLUSIONS: A considerable proportion of cases of lung cancer in men in Glasgow and the west of Scotland from 1975 to 1984 were asbestos related. Most of these may not have been considered for compensation by the Department of Social Security. Given the very small annual number of recorded cases of asbestosis this condition is probably not a prerequisite for the development of asbestos related lung cancer. A heightened awareness of the increasing incidence of asbestos related neoplasms and their more thorough investigation are recommended.}, } @article {pmid8503542, year = {1993}, author = {Bresnitz, EA and Gilman, MJ and Gracely, EJ and Airoldi, J and Vogel, E and Gefter, W}, title = {Asbestos-related radiographic abnormalities in elevator construction workers.}, journal = {The American review of respiratory disease}, volume = {147}, number = {6 Pt 1}, pages = {1341-1344}, doi = {10.1164/ajrccm/147.6_Pt_1.1341}, pmid = {8503542}, issn = {0003-0805}, support = {1K07 HL-02100-01A2/HL/NHLBI NIH HHS/United States ; }, mesh = {Analysis of Variance ; Asbestosis/*diagnostic imaging/epidemiology/physiopathology ; Chronic Disease ; *Elevators and Escalators/statistics & numerical data ; Humans ; Lung/*diagnostic imaging/physiopathology ; Male ; Middle Aged ; Philadelphia/epidemiology ; Radiography ; Respiratory Function Tests/statistics & numerical data ; Retrospective Studies ; Surveys and Questionnaires ; }, abstract = {Elevator construction workers are exposed to asbestos dust during construction and refurbishment work on older buildings. We screened a cohort of workers, all with greater than 20 yr of employment in the industry, with clinical examinations, chest radiography ("B" reader interpretations), and routine spirometry. Twenty of the 91 workers (22%) had evidence of pleural disease, but none of them had an interstitial process consistent with asbestosis. Of those with pleural thickening, 15 had bilateral circumscribed plaques and five had unilateral plaque formation. There were no cases of diffuse pleural thickening, benign pleural effusions, or mesothelioma identified in our cohort. The difference in the mean body mass index of those with pleural abnormalities (29.18 +/- 3.95) and those without (27.7 +/- 3.86) was not statistically significant (p = 0.135). We conclude that elevator construction workers have an increased risk for the development of asbestos-related pleural disease.}, } @article {pmid8404097, year = {1993}, author = {Papiris, SA and Maniati, MA and Sakellariou, K and Gosios, C and Kontogiannis, D and Constantopoulos, SH}, title = {Round atelectasis and Metsovo lung.}, journal = {Chest}, volume = {103}, number = {6}, pages = {1759-1762}, doi = {10.1378/chest.103.6.1759}, pmid = {8404097}, issn = {0012-3692}, mesh = {Aged ; Asbestosis/*complications/diagnostic imaging ; Environmental Exposure ; Female ; Greece ; Humans ; Male ; Middle Aged ; Pulmonary Atelectasis/diagnostic imaging/*etiology ; Radiography ; Retrospective Studies ; }, abstract = {Round (helical) atelectasis is one of the benign sequelae of occupational asbestos exposure. Environmental asbestos exposure does not differ from occupational in its pleural manifestations, but to our knowledge, round atelectasis has not been reported yet. In the present study, we present the clinical and radiologic findings of five individuals with round atelectasis. They were all born in the Metsovo area, northwest Greece, where environmental exposure to asbestos (tremolite) has been documented. All five had negative evaluation for malignancy. In addition, they have been followed up for one to four years and four of them are in good health, thus confirming round atelectasis as a benign, nonpremalignant condition. The fifth patient died of malignant pleural mesothelioma two years later, while the previously detected round atelectasis remained unchanged. We therefore consider that his mesothelioma was not related to the round atelectasis, although both were certainly related to the same environmental asbestos exposure.}, } @article {pmid8328475, year = {1993}, author = {Hiroshima, K and Murai, Y and Suzuki, Y and Goldstein, B and Webster, I}, title = {Characterization of asbestos fibers in lungs and mesotheliomatous tissues of baboons following long-term inhalation.}, journal = {American journal of industrial medicine}, volume = {23}, number = {6}, pages = {883-901}, doi = {10.1002/ajim.4700230606}, pmid = {8328475}, issn = {0271-3586}, support = {ES00928/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Asbestos/adverse effects/*analysis ; Asbestosis/complications/*pathology ; Atmosphere Exposure Chambers ; Body Burden ; Lung/chemistry/*pathology ; Mesothelioma/chemistry/etiology/*pathology ; Papio ; Peritoneal Neoplasms/chemistry/etiology/*pathology ; Pleural Neoplasms/chemistry/etiology/*pathology ; }, abstract = {Changes in the dimensions of inhaled asbestos fibers in the lung and translocation of intrapulmonary asbestos fibers into mesothelial tissues were investigated in 17 baboons (5 exposed to amosite, 4 to chrysotile, 5 to crocidolite, and 3 unexposed). The animals received different cumulative doses of asbestos by inhalation, followed by varying recovery periods (0-69 months). All asbestos types induced pulmonary asbestosis with severity directly related to the cumulative dose. There were a larger number of asbestos bodies in the lung of the amphibole-exposed animals than in those exposed to chrysotile. A tissue burden study, using transmission electron microscopy on 25-microns paraffin sections, ashed in a low-temperature asher, was performed. Intrapulmonary amosite fibers were shorter in geometric mean length compared with a standard amosite sample (UICC) (3.3 microns). In explanation, it was considered that long fibers might not be able to reach the lower respiratory tract and/or long fibers might be fragmented into shorter fibers. Further, in the amosite-exposed group, the mean length of intrapulmonary fibers increased with the extension of recovery period, suggesting that shorter fibers had been cleared from the lung. The chrysotile standard sample (UICC) had a shorter geometric mean length (1.1 microns) than amosite. The mean length of intrapulmonary chrysotile did not noticeably change with the extension of inhalation and recovery periods; however, the mean width decreased with the extension of these periods. This finding strongly suggested that separation of thick chrysotile fibers had occurred in the lung. The crocidolite standard sample (Transvaal) had a shorter geometric mean length (1.4 microns) than amosite.(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid8244299, year = {1993}, author = {Wang, C and Luo, S and Liu, X}, title = {[Pathologic observation of 298 rat mesotheliomas induced by asbestos].}, journal = {Hua xi yi ke da xue xue bao = Journal of West China University of Medical Sciences = Huaxi yike daxue xuebao}, volume = {24}, number = {2}, pages = {182-186}, pmid = {8244299}, issn = {0257-7712}, mesh = {Animals ; Asbestos ; Asbestos, Crocidolite/*adverse effects ; Asbestos, Serpentine/*adverse effects ; Mesothelioma/etiology/*pathology ; Pleural Neoplasms/etiology/*pathology ; Rats ; Rats, Wistar ; }, abstract = {Two hundred and ninety eight rat mesotheliomas induced by chrysotile or crocidolite were studies. The results demonstrated that tumor masses were scattered extensively. The appearance of tumor was polymorphous. According to the microscopic features, the 298 cases of mesothelioma could be histologically classified into three types, i.e. epithelial type, fibrous type and mixed cell type. The malignant mesothelioma is characteristic of its polymorphism and the clear cancernation of mesothelial cells.}, } @article {pmid8344608, year = {1993}, author = {Tamir, G and Sandbank, J and Rubin, M and Antebi, E}, title = {[Malignant peritoneal mesothelioma].}, journal = {Harefuah}, volume = {124}, number = {10}, pages = {613-6, 667}, pmid = {8344608}, issn = {0017-7768}, mesh = {Aged ; Combined Modality Therapy ; Humans ; Male ; *Mesothelioma/diagnosis/pathology/therapy ; *Peritoneal Neoplasms/diagnosis/pathology/therapy ; }, abstract = {Public attention has recently been devoted worldwide to malignant mesotheliomas and their relation to exposure to industrial materials, especially asbestos and its products. The more common form of the disease is the pleural type, while the peritoneal variant is rare, with an estimated incidence of less than 1:1,000,000 new cases per year. In contrast to the pleural type, the relationship of malignant peritoneal mesothelioma to exposure to asbestos is unclear. The differential diagnosis, based on clinical appearance and imaging techniques, is broad and the diagnosis is inconclusive, so that the diagnosis must be confirmed by histologic examination. Treatment is a combination of surgery, chemotherapy and irradiation. Contrary to occasional reports, the malignancy is fatal, death occurring within a few months of diagnosis. We present a 65-year-old man in whom malignant peritoneal mesothelioma was diagnosed. The presenting symptoms were a large abdominal mass involving the colon, and ascites. He died 5 months after the diagnosis was made.}, } @article {pmid8498359, year = {1993}, author = {Wylie, AG and Bailey, KF and Kelse, JW and Lee, RJ}, title = {The importance of width in asbestos fiber carcinogenicity and its implications for public policy.}, journal = {American Industrial Hygiene Association journal}, volume = {54}, number = {5}, pages = {239-252}, doi = {10.1080/15298669391354621}, pmid = {8498359}, issn = {0002-8894}, mesh = {Animals ; Asbestos/*adverse effects ; Carcinogenicity Tests ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; National Institute for Occupational Safety and Health, U.S. ; Particle Size ; *Public Policy ; United States ; }, abstract = {Evidence from human epidemiology, experimental animal implantation and inoculation studies, and lung burden studies show that fibers with widths greater than 1 micron are not implicated in the occurrence of lung cancer or mesothelioma. Furthermore, it is generally believed that certain fibers thinner than a few tenths of a micrometer must be abundant in a fiber population in order for them to be a causative agent for mesothelioma. These conclusions are fully consistent with the mineralogical characteristics of asbestos fibers, which, as fibrils, have widths of less than 1 micron and, as bundles, easily dissagregate into fibrils. Furthermore, the biological behavior of various habits of tremolite shows a clear dose-response relationship and provides evidence for a threshold between fiber width and tumor experience in animals. Public policy in regulating mineral fibers should incorporate this knowledge by altering the existing federal asbestos fiber definitions to reflect it.}, } @article {pmid8490544, year = {1993}, author = {Bianchi, C and Brollo, A and Zuch, C}, title = {Asbestos-related familial mesothelioma.}, journal = {European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP)}, volume = {2}, number = {3}, pages = {247-250}, doi = {10.1097/00008469-199305000-00009}, pmid = {8490544}, issn = {0959-8278}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Family Health ; Female ; Humans ; Lung Neoplasms/*etiology/*genetics ; Male ; Mesothelioma/*etiology/*genetics ; Middle Aged ; *Occupational Exposure ; }, abstract = {Familial mesotheliomas are reported in four pairs of patients. The group includes six men and two women, aged between 44 and 84 years. A blood relation (father-son) existed in two pairs only. All the present patients had histories of exposure to asbestos; in five cases exposure had occurred in the shipyards. Familial mesothelioma could represent a useful model for investigating genetic-environmental interactions.}, } @article {pmid8487573, year = {1993}, author = {Lewis, RJ}, title = {Mesothelioma: an incurable, nonsurgically treatable disease.}, journal = {The Journal of thoracic and cardiovascular surgery}, volume = {105}, number = {5}, pages = {943-944}, pmid = {8487573}, issn = {0022-5223}, mesh = {Asbestos/*adverse effects ; Humans ; *Mesothelioma ; *Pleural Neoplasms ; *Pneumonectomy ; }, } @article {pmid8392408, year = {1993}, author = {Kamino, K and Ernst, H and Mohr, U}, title = {Additional atypical malignant mesothelioma after intraperitoneal injection of mineral fibres in rats.}, journal = {Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie}, volume = {45}, number = {2-3}, pages = {65-66}, doi = {10.1016/S0940-2993(11)80461-6}, pmid = {8392408}, issn = {0940-2993}, mesh = {Animals ; Asbestos/*adverse effects ; Asbestos, Crocidolite ; Hyaluronic Acid/analysis ; Male ; Mesothelioma/*etiology/pathology ; Peritoneal Neoplasms/*etiology/pathology ; Rats ; Rats, Wistar ; }, } @article {pmid8390950, year = {1993}, author = {Hesterberg, TW and Miiller, WC and McConnell, EE and Chevalier, J and Hadley, JG and Bernstein, DM and Thevenaz, P and Anderson, R}, title = {Chronic inhalation toxicity of size-separated glass fibers in Fischer 344 rats.}, journal = {Fundamental and applied toxicology : official journal of the Society of Toxicology}, volume = {20}, number = {4}, pages = {464-476}, doi = {10.1006/faat.1993.1057}, pmid = {8390950}, issn = {0272-0590}, mesh = {Aerosols ; Animals ; Asbestos/toxicity ; Asbestos, Serpentine ; Body Burden ; Ceramics/toxicity ; *Glass ; Lung Diseases/*chemically induced/pathology ; Lung Neoplasms/chemically induced ; Male ; Particle Size ; Pulmonary Fibrosis/pathology ; Rats ; Rats, Inbred F344 ; }, abstract = {This study was initiated to determine the chronic biological effects in Fisher 344 rats of inhaled size-separated respirable fractions of fibrous glass (FG) having compositions representative of common building insulation wools. Rats were exposed using nose-only inhalation chambers, 6 hr/day, 5 days/week, for 24 months to three concentrations (3, 16, and 30 mg/m3) of two different compositions of FG (designated MMVF 10 and MMVF 11), or to filtered air (negative control). Fibrous glass findings were compared to those from a concurrent inhalation study of chrysotile asbestos and refractory ceramic fiber (RCF). The FGs used in this study were size selected to be largely respirable in the rat and the aerosol generation technique did not alter the dimensions of the fibers. Interim euthanizations took place at 3- to 6-month intervals to monitor progression of pulmonary changes. Fibers were recovered from digested lung tissue for determination of changes in fiber number and morphology. In animals exposed to 30 mg/m3 of MMVF 10 or MMVF 11, 4.2 +/- 0.9 x 10(5) and 6.4 +/- 3.1 x 10(5) fibers/mg dry lung tissue, respectively, were recovered after 24 months of exposure. Exposure to chrysotile asbestos (10 mg/m3) and to a lesser extent RCF (30 mg/m3) resulted in pulmonary fibrosis as well as mesothelioma and significant increases in lung tumors. FG exposure was associated with a nonspecific inflammatory response (macrophage response) in the lungs that did not appear to progress after 6-12 months of exposure. These cellular changes are reversible and are similar to the effects observed after inhalation of an inert dust. No lung fibrosis was observed in the FG-exposed animals. Further, FG exposure resulted in no mesotheliomas and no statistically significant increase in lung tumor incidence when compared to that of the negative control group. These findings, along with previous inhalation studies, suggest that respirable fibrous glass does not represent a significant hazard for fibrotic or neoplastic lung disease in humans.}, } @article {pmid8350778, year = {1993}, author = {Saebø, A and Elgjo, K and Lassen, J}, title = {Could development of malignant mesothelioma be induced by Yersinia enterocolitica infection?.}, journal = {Medical hypotheses}, volume = {40}, number = {5}, pages = {275-277}, doi = {10.1016/0306-9877(93)90005-b}, pmid = {8350778}, issn = {0306-9877}, mesh = {Adult ; Female ; Humans ; Mesothelioma/*etiology/pathology ; Middle Aged ; Models, Biological ; Pleural Neoplasms/*etiology/pathology ; Yersinia Infections/*complications/immunology ; *Yersinia enterocolitica ; }, abstract = {Two out of 458 hospitalized patients with Yersinia enterocolitica infection developed malignant mesothelioma of pleura viz. pericard; both died after a few months. Malignant mesothelioma of the pleura is commonly related to asbestos exposure, whereas pericardiac mesothelioma is an extremely uncommon neoplasm. The possible promotion of malignant mesothelioma by the Yersinia enterocolitica infection should not be disregarded, as the infection may launch chronic immunological reactions resembling those observed among asbestos workers.}, } @article {pmid8331837, year = {1993}, author = {Kumagai, S and Nakachi, S and Kurumatani, N and Nakagiri, S and Kataoka, A}, title = {[Estimation of asbestos exposure among workers repairing asbestos cement pipes used for conduits].}, journal = {Sangyo igaku. Japanese journal of industrial health}, volume = {35}, number = {3}, pages = {178-187}, doi = {10.1539/joh1959.35.178}, pmid = {8331837}, issn = {0047-1879}, mesh = {Adult ; Air Pollutants, Occupational/*analysis ; Asbestos/adverse effects/*analysis ; Humans ; Lung Neoplasms/etiology ; Male ; Mesothelioma/etiology ; *Occupational Exposure ; Risk ; Sewage ; }, abstract = {Asbestos cement pipes (ACPs) containing 15 to 20% chrysotile or crocidolite have been used for underground conduits. Even today 16.2% of all conduits in Japan are ACPs, though the production of ACPs was suspended in 1985. When such a conduit is accidentally damaged the workers belonging to the Waterworks Bureau of a local government cut off the damaged conduit using a high-speed disk cutter and replace it with a new conduit. This operation develops a cloud of dust and the workers involved run the risk of asbestos exposure. It was the aim of the present study to estimate asbestos exposure levels among these workers. First, in the experiment, we established the typical working conditions and requested an experienced worker to cut an ACP using a high-speed disc cutter in a hole dug in the ground as he routinely does. The experiment was repeated three times. During a bout of each experiment, dust was sampled at several points both inside and outside the hole. Second, a self-administered questionnaire survey was conducted to obtain information from the workers regarding their working conditions in cutting ACPs. The subjects of the survey were 1,048 men belonging to conduit repair sections of the Waterworks Bureau of 119 local governments. The results obtained can be summarized as follows. 1) Each bout of cutting ACPs required about five minutes. The concentration of asbestos fibers longer than 5 microns with 3:1 aspect ratio ranged from 48 to 170 fibers/ml (92 fibers/ml on an average) inside and 1.7 to 15 fibers/ml outside the hole. The concentration inside the hole exceeded the ceiling limit (10 fibers/ml) recommended for asbestos by the Japanese Association of Industrial Health. A concentration of 92 fibers/ml is equivalent to 0.96 fibers/ml as 8-h time-weighted average. 2) The number of subjects with experience of cutting ACPs was 849 (81.0%). The average length of service in conduit repair section was 14.2 yr. Based on the information obtained from each subject regarding the average working days per yr for each decade from 1946, the cumulative days to date expended in cutting ACPs was estimated to average 235 d, that is, 17 d per yr. Only 18.1% of the subjects used a protective respiratory device.(ABSTRACT TRUNCATED AT 400 WORDS)}, } @article {pmid8317897, year = {1993}, author = {Fusco, V and Ardizzoni, A and Merlo, F and Cinquegrana, A and Faravelli, B and De Palma, M and Chessa, L and Nicolò, G and Serra, M and Capaccio, A}, title = {Malignant pleural mesothelioma. Multivariate analysis of prognostic factors on 113 patients.}, journal = {Anticancer research}, volume = {13}, number = {3}, pages = {683-689}, pmid = {8317897}, issn = {0250-7005}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Environmental Exposure/adverse effects ; Humans ; Italy/epidemiology ; Mesothelioma/*mortality/pathology/therapy ; Middle Aged ; Multivariate Analysis ; Pleural Neoplasms/*mortality/pathology/therapy ; Prognosis ; Sex Factors ; Survival Analysis ; }, abstract = {We report on clinical features of 113 cases of pathologically confirmed Malignant Pleural Mesothelioma, observed in Genoa (Italy) between 1979 and 1985. Overall median survival was 10 months. Among the pretreatment variables studied (age, sex, asbestos exposure, pathological type, chest pain and dyspnea at the time of diagnosis), the only one of prognostic value in the univariate analysis was the histological subtype: median survivals were 12, 7 and 4 months for the patients in the epithelial, mixed, and fibrosarcomatous groups, respectively (p = 0.0012). A multivariate analysis confirmed the independent predictive power of the histotype (p = 0.0022). A review of literature data concerning prognostic factors in Malignant Pleural Mesothelioma is presented.}, } @article {pmid8252173, year = {1993}, author = {Ameille, J and Norès, JM and Bernard, N and Rémy, JM}, title = {Renal adenocarcinoma and exposure to asbestos.}, journal = {The European journal of medicine}, volume = {2}, number = {5}, pages = {317-318}, pmid = {8252173}, issn = {1165-0478}, mesh = {Adenocarcinoma, Clear Cell/*etiology ; Asbestos/*adverse effects ; Humans ; Kidney Neoplasms/*etiology ; Male ; Mesothelioma/etiology ; Middle Aged ; Neoplasms, Multiple Primary/*etiology ; Occupational Diseases/*etiology ; Pleural Neoplasms/etiology ; }, } @article {pmid8233654, year = {1993}, author = {Mirabella, F}, title = {[Pericardial mesothelioma. Evolution and update in the last decade].}, journal = {Pathologica}, volume = {85}, number = {1097}, pages = {377-386}, pmid = {8233654}, issn = {0031-2983}, mesh = {Asbestos/adverse effects ; Coronary Disease/etiology ; Female ; Heart Neoplasms/complications/*epidemiology/etiology ; Humans ; Male ; Mesothelioma/complications/*epidemiology/etiology ; Middle Aged ; Pericardium ; }, abstract = {Pericardial mesothelioma: epidemiological updating on the last decade. In the last decade, 109 cases of primitive malignant pericardial mesothelioma, histologically proved and reported in world medical literature have been added to the 206 cases described in a previous article. This illness, although rare, has been found more frequently in Japan (25 subjects) and in USSR (21 subjects). From the table in annex, the following points emerge: a) On average, pericardial mesothelioma tends to develop in fairly young people (compared to pleural or peritoneal mesothelioma). b) There is more proof that asbestos has an harmful effect on pericardial serosa. c) The most frequent clinical diagnoses refer mainly to acute pericarditis, constrictive pericarditis, cardiac tamponade and sometimes to various types of coronary heart disease, which autoptical examination reveals to be due to the presence of an external compression of the coronary arteries by pericardial mesothelioma. d) This illness, perhaps because of greater research and improved diagnostical means seems to be increasing when compared to the previous period (although this does not appear to be the case in our country).}, } @article {pmid8386370, year = {1993}, author = {Heintz, NH and Janssen, YM and Mossman, BT}, title = {Persistent induction of c-fos and c-jun expression by asbestos.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {90}, number = {8}, pages = {3299-3303}, pmid = {8386370}, issn = {0027-8424}, support = {HL14212/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Asbestos/*pharmacology/*toxicity ; Asbestos, Crocidolite ; Asbestos, Serpentine ; Blotting, Northern ; Cell Division/drug effects ; Cell Transformation, Neoplastic ; Cells, Cultured ; Cricetinae ; Dose-Response Relationship, Drug ; Epithelial Cells ; Epithelium/drug effects/physiology ; Gene Expression/drug effects ; Genes, fos/*drug effects ; Genes, jun/*drug effects ; Kinetics ; Models, Biological ; Pleura/cytology/*drug effects/physiology ; Proto-Oncogene Proteins c-fos/*biosynthesis/genetics ; Proto-Oncogene Proteins c-jun/*biosynthesis/genetics/metabolism ; RNA, Messenger/*metabolism ; Rats ; Rats, Inbred F344 ; Trachea/cytology/*drug effects/physiology ; }, abstract = {To investigate the mechanisms of asbestos-induced carcinogenesis, expression of c-fos and c-jun protooncogenes was examined in rat pleural mesothelial cells and hamster tracheal epithelial cells after exposure to crocidolite or chrysotile asbestos. In contrast to phorbol 12-myristate 13-acetate, which induces rapid and transient increases in c-fos and c-jun mRNA, asbestos causes 2- to 5-fold increases in c-fos and c-jun mRNA that persist for at least 24 hr in mesothelial cells. The induction of c-fos and c-jun mRNA by asbestos in mesothelial cells is dose-dependent and is most pronounced with crocidolite, the type of asbestos most pathogenic in the causation of pleural mesothelioma. Induction of c-jun gene expression by asbestos occurs in tracheal epithelial cells but is not accompanied by a corresponding induction of c-fos gene expression. In both cell types, asbestos induces increases in protein factors that bind specifically to the DNA sites that mediate gene expression by the AP-1 family of transcription factors. The persistent induction of AP-1 transcription factors by asbestos suggests a model of asbestos-induced carcinogenesis involving chronic stimulation of cell proliferation through activation of the early response gene pathway that includes c-jun and/or c-fos.}, } @article {pmid8514283, year = {1993}, author = {Mayall, FG and Goddard, H and Gibbs, AR}, title = {The frequency of p53 immunostaining in asbestos-associated mesotheliomas and non-asbestos-associated mesotheliomas.}, journal = {Histopathology}, volume = {22}, number = {4}, pages = {383-386}, doi = {10.1111/j.1365-2559.1993.tb00140.x}, pmid = {8514283}, issn = {0309-0167}, mesh = {Asbestos/*adverse effects ; Humans ; Immunohistochemistry ; Lung Neoplasms/chemically induced/metabolism/*pathology ; Mesothelioma/chemically induced/metabolism/*pathology ; Occupational Diseases/chemically induced/metabolism/*pathology ; Tumor Suppressor Protein p53/*analysis ; }, abstract = {It has been suggested that asbestos might have an important role in the development of p53 mutations in mesotheliomas. The objective of this study was to examine asbestos-associated mesotheliomas and non-asbestos-associated mesotheliomas to establish whether the frequency of p53 immunostaining and, by implication, p53 gene mutation is related to asbestos exposure. Immunopositivity for p53 was found in seven (44%) of the 16 mesotheliomas examined. The frequency was approximately the same in both the asbestos-associated mesotheliomas and the non-asbestos-associated mesotheliomas. It is concluded that the frequency of p53 immunostaining in mesotheliomas and, by implication, the frequency of p53 gene mutation is probably not related to asbestos exposure.}, } @article {pmid8511746, year = {1993}, author = {Krishna, J and Haqqani, MT}, title = {Liposarcomatous differentiation in diffuse pleural mesothelioma.}, journal = {Thorax}, volume = {48}, number = {4}, pages = {409-410}, pmid = {8511746}, issn = {0040-6376}, mesh = {Aged ; Asbestosis/pathology ; Female ; Humans ; Liposarcoma/*pathology ; Mesothelioma/*pathology ; Pleura/*pathology ; Pleural Neoplasms/*pathology ; }, abstract = {A case history is presented of a woman who died eight hours after hospital admission with severe breathlessness. At necropsy the right lung was encased in a thickened pleura with a large tumour. Histological examination of the tumour showed pleural mesothelioma with liposarcomatous differentiation. The lungs showed changes of asbestosis and the asbestos fibre count was significantly raised. Liposarcomatous differentiation in pleural mesothelioma has not been reported previously.}, } @article {pmid8480769, year = {1993}, author = {Roggli, VL and Pratt, PC and Brody, AR}, title = {Asbestos fiber type in malignant mesothelioma: an analytical scanning electron microscopic study of 94 cases.}, journal = {American journal of industrial medicine}, volume = {23}, number = {4}, pages = {605-614}, doi = {10.1002/ajim.4700230408}, pmid = {8480769}, issn = {0271-3586}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/analysis/*chemistry ; Electron Probe Microanalysis ; Female ; Humans ; Lung/chemistry/ultrastructure ; Lung Neoplasms/*chemistry/pathology ; Male ; Mesothelioma/*chemistry/pathology ; Middle Aged ; }, abstract = {Although the association between asbestos exposure and malignant mesothelioma is indisputable, controversy continues regarding the relative contribution of the various types of asbestos fibers to the development of mesothelioma. We examined the types of asbestos fibers recovered from lung parenchyma in more than 90 cases of malignant mesothelioma from the United States, using an analytical scanning electron microscope. Almost half of the patients were former asbestos insulators or shipyard workers. The fibers were recovered from lung tissues obtained at autopsy or surgical resection by means of a sodium hypochlorite digestion procedure. Amosite asbestos was identified in 81% of the cases and accounted for 58% of all fibers 5 microns or greater in length. Tremolite/actinolite/anthophyllite were identified in 55% of the cases and accounted for 10% of all fiber types. Chrysotile was identified in 21% of the cases and accounted for 3% of fibers exceeding 5 microns in length. Crocidolite was found in 16% of the cases and accounted for 3% of fibers exceeding 5 microns in length. Nonasbestos mineral fibers (commonly found in the lungs of the general population) were observed in 71% of the cases and accounted for 25% of all fibers 5 microns or greater in length. The findings in this study are at odds with the assertion that crocidolite asbestos is responsible for most mesotheliomas in the United States.}, } @article {pmid8462328, year = {1993}, author = {Antman, KH}, title = {Natural history and epidemiology of malignant mesothelioma.}, journal = {Chest}, volume = {103}, number = {4 Suppl}, pages = {373S-376S}, doi = {10.1378/chest.103.4_supplement.373s}, pmid = {8462328}, issn = {0012-3692}, mesh = {Asbestos/*adverse effects ; Combined Modality Therapy ; Female ; Humans ; *Lung Neoplasms/diagnosis/epidemiology/etiology/therapy ; Male ; *Mesothelioma/diagnosis/epidemiology/etiology/therapy ; Prognosis ; Risk Factors ; }, abstract = {Asbestos exposure constitutes the primary cause of pleural and peritoneal mesothelioma in humans. Risk relates to the duration and intensity of exposure. Thus, those exposed at younger ages are at higher lifetime risk. Families of asbestos workers exposed to asbestos on hair and clothing as well as to asbestos items brought home from the workplace are also at risk, as are employees working in the same vicinity as asbestos workers. The public health significance of exposure from asbestos in public and private buildings remains controversial. Malignant mesothelioma is difficult to diagnose and carries a poor prognosis. Chemotherapy with single or multiple agents has thus far been disappointing, but doxorubicin and cisplatin or mitomycin and cisplatin are probably most active with response rates in measurable disease of 25%. Palliative radiotherapy is also problematic since differences between tumor cytotoxicity and pulmonary tolerance are small and radiation pneumonitis may significantly impair quality of life.}, } @article {pmid8131480, year = {1993}, author = {Behling, CA and Wolf, PL and Haghighi, P}, title = {AIDS and malignant mesothelioma--is there a connection?.}, journal = {Chest}, volume = {103}, number = {4}, pages = {1268-1269}, doi = {10.1378/chest.103.4.1268}, pmid = {8131480}, issn = {0012-3692}, mesh = {Acquired Immunodeficiency Syndrome/*complications ; Adult ; Humans ; Lung/pathology ; Male ; Mesothelioma/*complications/pathology ; Pleural Neoplasms/*complications/pathology ; }, abstract = {A 35-year-old male homosexual, a former intravenous drug abuser, was found to be human immunodeficiency virus (HIV) positive in 1984. He developed AIDS in 1987 and began treatment with zidovudine in 1989. One year later he developed left apical pleural blebs, a pneumothorax and an exudative pleural effusion. A malignant mesothelioma developed at the pleural blebs in the left apex. He was treated with adriamycin but rapid progression of the malignancy occurred and he died three months later. At autopsy, a malignant mesothelioma, causing respiratory failure and death, was found. The patient had no exposure to asbestos and asbestosis was not present at autopsy. We postulate that the development of malignant mesothelioma was probably related to HIV immune suppression or HIV and/or cytomegalovirus or zidovudine and is a complication of AIDS similar to the development of other malignant neoplasms in patients with AIDS.}, } @article {pmid8497827, year = {1993}, author = {Dawson, A and Gibbs, AR and Pooley, FD and Griffiths, DM and Hoy, J}, title = {Malignant mesothelioma in women.}, journal = {Thorax}, volume = {48}, number = {3}, pages = {269-274}, pmid = {8497827}, issn = {0040-6376}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Female ; Humans ; Mesothelioma/complications/*epidemiology/pathology ; Middle Aged ; Occupational Exposure/adverse effects ; Peritoneal Neoplasms/pathology ; Pleural Neoplasms/pathology ; Pulmonary Fibrosis/complications ; Sex Factors ; }, abstract = {BACKGROUND: Malignant mesothelioma reportedly shows different epidemiology and pathology in females, and a proportion are believed to arise spontaneously.

METHODS: One hundred and seventy seven cases of malignant mesothelioma in females were reviewed, examined by histochemistry and immunohistochemistry, assessed for asbestosis and lung fibre burden by transmission electron microscopy with energy dispersive x ray analysis, and compared with 31 female controls.

RESULTS: Two of one hundred and three cases tested for carcinoembryonic antigen were positive and were excluded from further analysis. Tumour cases showed increased amphibole burdens; in those in whom exposure information was known, 74 (80%) of 93 patients had a history of exposure to asbestos. Seventy two (47%) of 152 patients had lung fibrosis. Tumour site and histological type were little different from those reported in adult males. Mixed type histological pattern, lung fibrosis, and peritoneal site were associated with heavier lung asbestos burdens, but not exclusively. Thirty five (30%) of 117 patients had amphibole burdens of less than 2 x 10(6) fibres/g; the sites affected and the histological pattern of tumours in this group were similar to those in cases with amphibole fibre counts of > or = 2 x 10(6)/g lung. A higher lung amphibole burden than the mean burden in control females was found in 115 (98%) of 117 patients tested.

CONCLUSIONS: The pathology of malignant mesothelioma appears to be similar in women and in men, and in cases associated and unassociated with asbestos.}, } @article {pmid8472817, year = {1993}, author = {Jaurand, MC and Bignon, J}, title = {Focus on mesothelioma and the mesothelial cell.}, journal = {The European respiratory journal}, volume = {6}, number = {3}, pages = {319-321}, pmid = {8472817}, issn = {0903-1936}, mesh = {Animals ; Asbestos/adverse effects ; Diagnosis, Differential ; Epithelial Cells ; Humans ; Incidence ; Male ; *Mesothelioma/diagnosis/epidemiology/therapy ; Mice ; Occupational Diseases/epidemiology ; Prognosis ; }, } @article {pmid8428109, year = {1993}, author = {Saitoh, K and Muto, H and Hachiya, N and Takizawa, Y}, title = {Asbestos body and fiber concentrations in pathological autopsy tissues of patients with malignant peritoneal mesothelioma.}, journal = {Bulletin of environmental contamination and toxicology}, volume = {50}, number = {3}, pages = {325-332}, pmid = {8428109}, issn = {0007-4861}, mesh = {Adult ; Asbestos/adverse effects/*isolation & purification ; Case-Control Studies ; Female ; Humans ; Intestine, Large/*pathology ; Lung/*pathology ; Male ; Mesothelioma/etiology/*pathology ; Microscopy, Electron, Scanning ; Middle Aged ; *Omentum ; Peritoneal Neoplasms/etiology/*pathology ; }, } @article {pmid8384961, year = {1993}, author = {Yesner, R}, title = {Pathogenesis and pathology.}, journal = {Clinics in chest medicine}, volume = {14}, number = {1}, pages = {17-30}, pmid = {8384961}, issn = {0272-5231}, mesh = {Adenocarcinoma/etiology/pathology ; Asbestos/*adverse effects ; Carcinoma, Non-Small-Cell Lung/pathology ; Carcinoma, Small Cell/pathology ; Carcinoma, Squamous Cell/etiology/pathology ; Female ; Humans ; Lung Neoplasms/*etiology/genetics/pathology ; Male ; Mesothelioma/pathology ; Oncogenes/*genetics ; Radon/*adverse effects ; Smoking/*adverse effects ; }, abstract = {Pathogenesis consists of a discussion of the role of oncogenes and suppressor genes on small-cell lung cancer and non-small-cell lung cancer as well as the external factors of smoking (active and passive), asbestos, and radon. Pathology consists of discussion of squamous cell lung cancer, adenocarcinoma and bronchoalveolar carcinoma, large cell carcinoma (including giant cell and clear cell variants), and neuroendocrine tumors. Mesotheliomas are discussed as is the role of monoclonal antibodies in diagnosis.}, } @article {pmid8381434, year = {1993}, author = {Resnick, D and Freedman, NJ and Xu, S and Krieger, M}, title = {Secreted extracellular domains of macrophage scavenger receptors form elongated trimers which specifically bind crocidolite asbestos.}, journal = {The Journal of biological chemistry}, volume = {268}, number = {5}, pages = {3538-3545}, pmid = {8381434}, issn = {0021-9258}, support = {HL41484/HL/NHLBI NIH HHS/United States ; }, mesh = {Amidohydrolases ; Animals ; Asbestos/*metabolism ; Asbestos, Crocidolite ; Base Sequence ; CHO Cells ; Cattle ; Cell Line ; Chromatography, Gel ; Cricetinae ; Macromolecular Substances ; Macrophages/*immunology ; *Membrane Proteins ; Molecular Sequence Data ; Molecular Weight ; Oligodeoxyribonucleotides ; Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase ; Polymerase Chain Reaction ; Protein Binding ; Protein Structure, Secondary ; Receptors, Immunologic/*genetics/isolation & purification/*metabolism ; *Receptors, Lipoprotein ; Receptors, Scavenger ; Recombinant Proteins/isolation & purification/metabolism ; Scavenger Receptors, Class B ; Transfection ; }, abstract = {Macrophage scavenger receptors, which have been implicated in the development of atherosclerosis and other macrophage-mediated events, are trimeric integral membrane glycoproteins whose extracellular domains have been predicted to include alpha-helical coiled-coil, collagenous and globular structures. To elucidate further the structural and functional properties of these receptors, we generated transfected Chinese hamster ovary cells which express secreted extracellular domains of the type I and type II bovine scavenger receptors and developed a solid-phase bead-binding assay to assess their ligand-binding properties. The secreted receptors exhibited the distinctive high-affinity, broad polyanionic ligand-binding specificity and the pH dependence of binding which characterize the membrane-anchored cell-surface forms of the receptors. Both the type I and type II secreted receptors were trimeric glycoproteins comprising disulfide-linked dimers and noncovalently associated monomers. Gel filtration and glycerol-gradient centrifugation established that the type II trimers were highly elongated and did not associate into higher order oligomers at the low concentrations used in these experiments. Crocilodite asbestos, which is phagocytosed by alveolar macrophages and can cause asbestosis and mesothelioma, bound efficiently to secreted type I receptors and less well to the type II receptors. This binding was specific in that it was competed by a variety of well established scavenger receptor ligands but not by negative controls. These studies have identified a new type of insoluble scavenger receptor ligand, and have raised the possibility that scavenger receptors may play a role in mediating the physiological and pathological interactions of inspired particles with alveolar macrophages.}, } @article {pmid8460968, year = {1993}, author = {Driscoll, TR and Baker, GJ and Daniels, S and Lee, J and Thompson, R and Ferguson, DA and Leigh, J}, title = {Clinical aspects of malignant mesothelioma in Australia.}, journal = {Australian and New Zealand journal of medicine}, volume = {23}, number = {1}, pages = {19-25}, doi = {10.1111/j.1445-5994.1993.tb00532.x}, pmid = {8460968}, issn = {0004-8291}, mesh = {Aged ; Asbestos/adverse effects ; Australia/epidemiology ; Female ; Humans ; Male ; *Mesothelioma/diagnosis/epidemiology/etiology/secondary ; Middle Aged ; Registries ; Survival Analysis ; *Thoracic Neoplasms/diagnosis/epidemiology/etiology ; }, abstract = {Australia is currently experiencing an epidemic of malignant mesothelioma. The clinical aspects of malignant mesothelioma were investigated in 295 Australian patients as part of a national study of the disease. Most patients were male (91%), with the mean age at diagnosis being 64 years. The predominant cell type was epithelial (38%) and the majority of primary tumours arose from the pleura (94%). Mean survival was poor (17.6 months from first symptom; 11.8 months from diagnosis). Patients with a pleural primary tumour were more likely to present with dyspnoea, chest pain and cough; to have a pleural effusion diagnosed radiologically; and to have metastatic spread. Patients with a peritoneal primary tumour were more likely to present with weight loss, loss of appetite, abdominal pain and ascites; to have radiologic evidence of asbestos exposure; and to have spread along a needle track created during a diagnostic tap. A minority of patients had past thoracic conditions, or radiologic findings, specifically related to previous asbestos exposure. About one fifth of patients had no known asbestos exposure. Forty-one per cent of subjects received some form of chemotherapy, radiotherapy and/or surgery, but no formal disease staging had been documented for any patient. Proper controlled trials of secondary and tertiary treatments in malignant mesothelioma are now needed.}, } @article {pmid8443784, year = {1993}, author = {Lenz, SP and Green, FH and Murphy, PG and Lee, M and Hart, DA}, title = {Expression of plasminogen activator and plasminogen activator inhibitor by rat mesothelioma induced by asbestos.}, journal = {Cancer letters}, volume = {68}, number = {2-3}, pages = {119-127}, doi = {10.1016/0304-3835(93)90137-x}, pmid = {8443784}, issn = {0304-3835}, mesh = {Animals ; Asbestos ; Cell Adhesion ; Cell Division ; Chromatography ; Culture Media, Conditioned ; Isoelectric Focusing ; Mesothelioma/etiology/*metabolism ; Plasminogen Activators/*metabolism ; Plasminogen Inactivators/*metabolism ; Rats ; Rats, Inbred F344 ; Tumor Cells, Cultured ; }, abstract = {We have investigated the expression of plasminogen activators (PAs) and PA inhibitors (PAIs) by an asbestos-induced mesothelioma. Using zymographic, immunological and biochemical techniques it was demonstrated that cell lines derived from the tumor express high levels of PAI and low levels of a UK-like PA. Adherent and partially non-adherent variants of the mesothelioma expressed indistinguishable amounts of PAI and UK. Based on partial biochemical characterization, the PAI secreted by the mesothelioma cells was a set of PAIs which consisted of PAI-1 in addition to other species. These observations indicate that the difference in growth phenotype of the adherent and partially non-adherent lines was not due to detectable differences in PA and PAI expression.}, } @article {pmid8421723, year = {1993}, author = {Müller, NL}, title = {Imaging of the pleura.}, journal = {Radiology}, volume = {186}, number = {2}, pages = {297-309}, doi = {10.1148/radiology.186.2.8421723}, pmid = {8421723}, issn = {0033-8419}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Carcinoma, Bronchogenic/diagnosis ; Diagnosis, Differential ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Mesothelioma/diagnosis/diagnostic imaging ; Middle Aged ; Pleura/pathology ; Pleural Diseases/*diagnosis/diagnostic imaging ; Pleural Effusion/diagnosis/diagnostic imaging/therapy ; Pleural Neoplasms/diagnosis/etiology ; Tomography, X-Ray Computed ; Ultrasonography ; }, } @article {pmid8486752, year = {1993}, author = {Huncharek, M}, title = {Exporting asbestos: disease and policy in the developing world.}, journal = {Journal of public health policy}, volume = {14}, number = {1}, pages = {51-65}, pmid = {8486752}, issn = {0197-5897}, mesh = {*Asbestos/adverse effects ; Developing Countries ; *Health Policy ; Humans ; *Industry ; }, abstract = {The health effects of asbestos are well known, with lung cancer, mesothelioma and asbestosis recognized as the most common causes of mortality and morbidity among exposed populations. Recognition of these hazards coupled with an explosion of litigation against asbestos manufacturers brought by injured workers has resulted in declining markets for this commodity in the U.S. and other Western democracies. With Western markets for asbestos decreasing, the developing world has become the target of asbestos exporters in an attempt to revitalize an industry in decline. This paper discusses the trends in worldwide asbestos markets over the last two decades and the serious health implications of policies directed at establishing viable markets for this commodity in developing nations.}, } @article {pmid8460596, year = {1993}, author = {Fujii, Y and Masuda, M and Hirokawa, M and Matsushita, K and Asakura, S}, title = {[A case of benign mesothelioma of the tunica vaginalis testis].}, journal = {Hinyokika kiyo. Acta urologica Japonica}, volume = {39}, number = {1}, pages = {89-92}, pmid = {8460596}, issn = {0018-1994}, mesh = {Diagnosis, Differential ; Humans ; Male ; Mesothelioma/*diagnosis/surgery ; Middle Aged ; Orchiectomy ; Testicular Neoplasms/*diagnosis/surgery ; }, abstract = {A case of benign mesothelioma of the tunica vaginalis testis is described. A 56-year-old man with no history of asbestos exposure presented with a swelling of the left scrotal content. A physical examination revealed a hydrocele and an induration on the left epididymal head. A cytological examination of the hydrocele fluid demonstrated clusters of mesothelial cells without evidence of malignancy (class III). Left inguinal orchiectomy was performed because a 15 mm papillary pedunculated tumor was seen on the surface of the tunica vaginalis. A microscopic examination showed the papillary and glandular structures composed of cuboidal cells with no cytologic atypia, which were consistent with benign mesothelioma. The patient remains well and free of recurrent disease 10 years after operation.}, } @article {pmid8451494, year = {1993}, author = {Ameille, J and Bernard, N and Nores, JM and Capron, F and Rémy, JM}, title = {[Pleural mesothelioma and renal adenocarcinoma simultaneously discovered in a subject exposed to asbestos].}, journal = {Revue des maladies respiratoires}, volume = {10}, number = {1}, pages = {42-43}, pmid = {8451494}, issn = {0761-8425}, mesh = {Adenocarcinoma/chemically induced/complications/*diagnostic imaging ; Asbestos/*adverse effects ; Humans ; Kidney Neoplasms/chemically induced/complications/*diagnostic imaging ; Male ; Mesothelioma/chemically induced/complications/*diagnostic imaging ; Middle Aged ; *Occupational Exposure ; Pleural Neoplasms/chemically induced/complications/*diagnostic imaging ; Radiography ; Smoking/adverse effects ; }, abstract = {We report a case of pleural mesothelioma and renal adenocarcinoma, discovered simultaneously in a patient aged sixty, who had had occupational exposure to asbestos between the ages of fourteen and twenty-eight. The contribution of asbestos in the occurrence of these malignant tumours is discussed in relation to the information contained in the literature.}, } @article {pmid8398278, year = {1993}, author = {Damhuis, RA and van Gelder, T}, title = {Malignant mesothelioma in the Rotterdam area, 1987-1989.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {29A}, number = {10}, pages = {1478-1479}, doi = {10.1016/0959-8049(93)90024-a}, pmid = {8398278}, issn = {0959-8049}, mesh = {Adolescent ; Adult ; Aged ; Asbestos/adverse effects ; Child ; Child, Preschool ; Engineering ; Female ; Humans ; Incidence ; Infant ; Infant, Newborn ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Netherlands/epidemiology ; Occupational Diseases/etiology ; Pleural Neoplasms/*epidemiology ; Ships ; }, abstract = {Malignant mesothelioma is commonly regarded as a rare disease. This, however, does not apply to the Rotterdam area. Registry data show an age-standardised incidence rate (per 100,000 per year, world standard population) of pleural cancer in men of 6.2 for the period 1987-1989. This is substantially higher than thus far reported by other cancer registries. Similar observations may be expected in other areas with shipbuilding or asbestos industries.}, } @article {pmid8333711, year = {1993}, author = {Sans, N and Cnudde, F and Cnudde, F and Chevallier, J and Mathieu, S and Giron, J and Railhac, JJ}, title = {[A rare peritoneal tumor: malignant mesothelioma].}, journal = {Annales de radiologie}, volume = {36}, number = {2}, pages = {118-124}, pmid = {8333711}, issn = {0003-4185}, mesh = {Aged ; Diagnosis, Differential ; Female ; Humans ; Mesothelioma/*diagnosis/diagnostic imaging/surgery ; Peritoneal Neoplasms/*diagnosis/diagnostic imaging/surgery ; Tomography, X-Ray Computed ; Ultrasonography ; }, abstract = {A peritoneal mesothelioma is described. The diagnosis was established by histological study. The clinical and radiological presentation are nonspecific. Contact with asbestos fibers is rarely reported and not obtained in this case. The clinical, radiological, histological presentations and therapeutic aspects are discussed.}, } @article {pmid8279191, year = {1993}, author = {Gurtner, F and Minder, CE}, title = {[Cancer mortality according to occupation: implications for prevention].}, journal = {Sozial- und Praventivmedizin}, volume = {38 Suppl 2}, number = {}, pages = {S137-9}, pmid = {8279191}, issn = {0303-8408}, mesh = {Aged ; Construction Materials/adverse effects ; Humans ; Interior Design and Furnishings ; Male ; Mesothelioma/etiology/*mortality ; Middle Aged ; Occupational Diseases/*mortality/prevention & control ; Paranasal Sinus Neoplasms/etiology/*mortality ; Pleural Neoplasms/etiology/*mortality ; Switzerland/epidemiology ; Wood ; }, abstract = {The implications for the prevention of cancer and for health promotion at work is illustrated with two examples from an analysis of cancer mortality by occupation of Swiss men, 1979-1982. The classical approach of industrial medicine to the reduction of pollutants via legislative, technical and informative measures is applied in the case of sinonasal carcinoma and pleural mesothelioma that is increased with furniture-makers. The fact that a comparable cancer mortality pattern linked to miscellaneous factors like smoking, asbestos, cement dust, alcohol, chemicals, nutrition etc. is observed for the various jobs of the building industry, requires an extensive health promotion effort uniting industrial medicine with organizational and individual approaches.}, } @article {pmid8256032, year = {1993}, author = {Harf, R and Laval, I and Davezies, P and Prost, G}, title = {[Unrecognized occupational risk of pleural mesothelioma. The example of the Rhône-Alps region].}, journal = {Revue des maladies respiratoires}, volume = {10}, number = {5}, pages = {453-458}, pmid = {8256032}, issn = {0761-8425}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Female ; France/epidemiology ; Humans ; Incidence ; Male ; Mesothelioma/diagnosis/*epidemiology/*etiology ; Middle Aged ; Occupational Diseases/diagnosis/*epidemiology/*etiology ; Occupational Exposure ; Occupational Medicine ; Pleural Neoplasms/diagnosis/*epidemiology/*etiology ; Time Factors ; Workers' Compensation ; }, abstract = {A retrospective study of pleural mesothelioma diagnosed between 1980 and 1988 in the Rhône-Alpes région allowed to identify 224 cases. From the 187 patients in which occupational history was available 105 (56%) had been exposed to asbestos at work and 44 had been recognised as occupation disease and compensated. These data illustrate that the real incidence of the disease is largely underestimated and that legal procedure for occupational disease recognition is highly deficient.}, } @article {pmid8235025, year = {1993}, author = {Rey, F and Viallat, JR and Boutin, C and Farisse, P and Billon-Galland, MA and Hereng, P and Dumortier, P and De Vuyst, P}, title = {[Environmental mesotheliomas in northeast Corsica].}, journal = {Revue des maladies respiratoires}, volume = {10}, number = {4}, pages = {339-345}, pmid = {8235025}, issn = {0761-8425}, mesh = {Adult ; Aged ; Aged, 80 and over ; Air Pollutants/analysis ; Animals ; *Asbestos/analysis ; Asbestos, Amphibole/analysis ; Asbestos, Serpentine/analysis ; Bronchoalveolar Lavage Fluid/chemistry ; Dog Diseases/*chemically induced/diagnosis/*epidemiology ; Dogs ; *Environmental Exposure ; Female ; France/epidemiology ; Goat Diseases/*chemically induced/diagnosis/*epidemiology ; Goats ; Humans ; Incidence ; Male ; Mesothelioma/diagnosis/*epidemiology/*etiology/pathology/veterinary ; Middle Aged ; *Mining ; Occupations ; Pleural Neoplasms/diagnosis/*epidemiology/*etiology/pathology/veterinary ; *Population Surveillance ; Retrospective Studies ; Risk Factors ; Survival Rate ; Thoracoscopy ; }, abstract = {Since 1980, we have collected fourteen cases of mesothelioma induced by environmental exposure to asbestos, going back to childhood in patients from north-east Corsica, in a region which was remote from the asbestos mine of Canari. There were eight men and six women with a mean age of 69.5 +/- 4 years. Six patients presented with bilateral calcified pleural plaques as evidence of environmental exposure. The mineral analysis carried out on five patients (four had thoracoscopies and one an alveolar lavage), showed a moderate deposit of chrysotile (0.3 to 3.4 x 10(6) fibres per gram of dry tissue), and elevated level of tremolite (1.4 to 62 x 10(6) fibres/g). The ambient dosage of asbestos has confirmed the existence of environmental pollution by chrysotile fibres and above all by tremolite. In addition, the same type of fibres have been identified in the parietal pleural of animals subjected to the same risk. In this region, the risk is estimated, on the basis of our results, as 10 cases of mesothelioma per 100,000 inhabitants per year.}, } @article {pmid8219898, year = {1993}, author = {Woźniak, H and Wiecek, E and Stetkiewicz, J and Wyszyńska, K}, title = {Experimental carcinogenicity and mutagenicity of non-asbestos natural fibres--preliminary report.}, journal = {Polish journal of occupational medicine and environmental health}, volume = {6}, number = {1}, pages = {55-60}, pmid = {8219898}, issn = {0867-8383}, mesh = {Animals ; Asbestos, Serpentine/*toxicity ; Carcinogenicity Tests ; Carcinogens/*toxicity ; Dust ; Female ; Male ; Mice ; Mice, Inbred BALB C ; Mutagenicity Tests ; Rats ; Rats, Wistar ; Sister Chromatid Exchange ; }, abstract = {The aim of this investigation was to quantify the carcinogenic and mutagenic activity of antigorite occurring in the form of admixtures in different mineral raw materials (serpentinite, magnesite, dolomite and nickel ore). The carcinogenicity of dusts was evaluated after intraperitoneal injections of 5 mg (mice) or 20 mg (rats) of dust suspended in saline. A pathomorphological examination was performed in all the dead animals. For two raw materials--serpentinite and nickel ore--their mutagenic potency was investigated (SCE test was used in this study). Results obtained in the experiments on animals (rats and mice) showed that the biological aggressiveness of the mineral raw materials tested was associated with the content of antigorite fibres. Particularly the frequency of mesothelioma (5-85%) was related to the number of antigorite fibres longer than 5 microns. Both of the investigated raw materials (serpentinite and nickel ore) were mutagenic in the SCE test.}, } @article {pmid8216837, year = {1993}, author = {Branchaud, RM and Garant, LJ and Kane, AB}, title = {Pathogenesis of mesothelial reactions to asbestos fibers. Monocyte recruitment and macrophage activation.}, journal = {Pathobiology : journal of immunopathology, molecular and cellular biology}, volume = {61}, number = {3-4}, pages = {154-163}, doi = {10.1159/000163784}, pmid = {8216837}, issn = {1015-2008}, support = {K04 ES 00127/ES/NIEHS NIH HHS/United States ; R01 ES 03721/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; *Asbestos ; Asbestosis/*pathology ; Cell Adhesion ; Cell Movement ; Cells, Cultured ; Disease Models, Animal ; In Vitro Techniques ; Injections, Intraperitoneal ; Lectins/metabolism ; Macrophage Activation ; Macrophages/*cytology ; Male ; Mice ; Mice, Inbred C57BL ; Microscopy, Electron, Scanning ; Monocytes/cytology ; Peritoneal Cavity/cytology ; Phagocytosis ; *Plant Lectins ; Silicon Dioxide/administration & dosage ; Titanium/administration & dosage ; }, abstract = {Exposure to asbestos fibers leads to a variety of mesothelial reactions: pleural effusions, fibrotic pleural plaques, and malignant mesotheliomas. An animal model was developed to reproduce these lesions in C57B1/6 mice using weekly intraperitoneal injections of asbestos fibers. After exposure to asbestos fibers, monocytes were recruited into the abdominal cavity and acquired the characteristics of inflammatory or nonspecifically activated macrophages. Nontoxic titanium dioxide or toxic silica particles did not produce activation of the free peritoneal macrophage population. Aggregates of asbestos fibers were found on the diaphragm and other peritoneal surfaces within only 24 h after a single injection. Macrophage recruitment to these sites peaked between 3 and 5 days, while activated macrophages persisted up to 14 days. Recruitment and activation of macrophages by repeated exposures to asbestos fibers may contribute to chronic damage of the mesothelial lining caused by these mineral fibers.}, } @article {pmid8132389, year = {1993}, author = {Fletcher, AC and Engholm, G and Englund, A}, title = {The risk of lung cancer from asbestos among Swedish construction workers: self-reported exposure and a job exposure matrix compared.}, journal = {International journal of epidemiology}, volume = {22 Suppl 2}, number = {}, pages = {S29-35}, doi = {10.1093/ije/22.supplement_2.s29}, pmid = {8132389}, issn = {0300-5771}, mesh = {Asbestos/*adverse effects ; Case-Control Studies ; Construction Materials/*adverse effects ; Epidemiologic Methods ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/etiology ; *Occupational Exposure ; Pleural Neoplasms/etiology ; Risk Factors ; Sensitivity and Specificity ; Sweden/epidemiology ; }, abstract = {A total of 719 lung cancers were identified in a follow-up of 135,000 Swedish construction workers interviewed during 1971-1974 by occupational health nurses as part of a routine health check-up. These were analysed in a matched case-control study nested within this cohort, to compare different methods of characterizing exposure to asbestos. Self-reported exposure was contrasted with a job exposure matrix (JEM) of five levels of exposure intensity, applied to the job at the time of health check-up. Smoking adjusted odds ratios were computed and the JEM performed better than self-reported exposure, in being able to discriminate high risk subgroups. The same pattern was evident in a parallel analysis of 41 mesotheliomas. However both measures appeared subject to misclassification, and the question put seemed to pick up the use of asbestos cement products more effectively than asbestos insulation products. It is concluded that a simple JEM can be more reliable than a simple question, but that both should be much more detailed, to take account of different types of asbestos exposure and their variation over time.}, } @article {pmid8110978, year = {1993}, author = {Matsuo, T and Ito, H and Anami, M and Ikeda, T and Nishihata, S}, title = {Malignant peritoneal mesothelioma with squamous metaplasia.}, journal = {Cytopathology : official journal of the British Society for Clinical Cytology}, volume = {4}, number = {6}, pages = {373-378}, doi = {10.1111/j.1365-2303.1993.tb00117.x}, pmid = {8110978}, issn = {0956-5507}, mesh = {Adult ; Asbestos/adverse effects ; Carcinoma, Squamous Cell/etiology/*pathology ; Humans ; Immunohistochemistry ; Male ; Mesothelioma/etiology/*pathology ; Peritoneal Neoplasms/etiology/*pathology ; }, } @article {pmid8107699, year = {1993}, author = {Churg, A}, title = {Asbestos-related disease in the workplace and the environment: controversial issues.}, journal = {Monographs in pathology}, volume = {}, number = {36}, pages = {54-77}, pmid = {8107699}, issn = {0077-0922}, mesh = {Asbestos/adverse effects/chemistry ; Asbestos, Amphibole/adverse effects ; Asbestos, Serpentine/adverse effects ; *Asbestosis/diagnosis ; Diagnosis, Differential ; Environmental Exposure ; Humans ; Lung Neoplasms/chemically induced ; Mesothelioma/chemically induced ; }, abstract = {Asbestos-related diseases continue to be sources of controversy for epidemiologist, clinician, and pathologist. Most investigators agree that the different fiber types behave differently in the lung, with chrysotile being rapidly removed, and amphibole persisting. These differences in biologic behavior probably account for the much greater disease potential of amphibole (amosite and crocidolite) compared with chrysotile asbestos, particularly in regard to mesothelioma induction in man. Asbestosis is defined as diffuse interstitial fibrosis of the lung caused by asbestos exposure, and this is the only condition to which the term asbestosis should be applied. The classical pathologic diagnostic criteria for asbestosis, namely the presence of diffuse interstitial fibrosis resembling usual interstitial pneumonia, and asbestos bodies visible in ordinary tissue sections, have proved to withstand the test of time. Cases without asbestos bodies visible in routine or iron-stained tissue sections almost never turn out to be asbestosis. It should be remembered that workers with asbestos exposure develop all of the interstitial lung diseases to which the remainder of the populace is subject; some of these conditions are treatable and should not be misdiagnosed as asbestosis, which is not treatable. There is strong epidemiologic and pathologic evidence that the only association of asbestos exposure and lung cancer is the association of asbestosis and lung cancer. Thus, a lung cancer should only be attributed to asbestos exposure when asbestosis is present on clinical or pathologic grounds. The histologic type and location of the tumor are irrelevant in this regard. Analytical electron microscopy indicates that chrysotile asbestos does induce mesothelioma in man, but that extremely high levels of retained fibers, levels as high as those seen in cases of asbestosis, are required for this event to occur. The weight of the evidence suggests that exposure of the general population to the very low levels of chrysotile that are found in some public building (levels not greatly different from ambient air) will never produce mesothelioma, asbestosis, or lung cancer because these diseases all appear to require quite high-level occupational chrysotile exposure. Even if one accepts the ideas (probably wrong) that any level of asbestos exposure carries a risk of cancer, and that mathematical extrapolation of risk from high-level occupational exposure to low-level building exposure is scientifically valid, the calculated risks are much smaller than real everyday risks such as driving to work. Thus, exposure to asbestos at environmental levels appears to produce no real dangers to health.}, } @article {pmid8075928, year = {1993}, author = {Pylev, LN and Stadnikova, NM and Kleĭmenova, EV}, title = {[Intermittent effect of asbestos dust and pleural carcinogenesis in rats].}, journal = {Meditsina truda i promyshlennaia ekologiia}, volume = {}, number = {1}, pages = {15-17}, pmid = {8075928}, issn = {1026-9428}, mesh = {Animals ; Asbestos/administration & dosage/*toxicity ; Drug Administration Schedule ; *Dust ; Female ; Male ; Mesothelioma/epidemiology/*etiology ; Models, Biological ; Pleural Neoplasms/epidemiology/*etiology ; Rats ; Rats, Wistar ; Time Factors ; }, abstract = {Frequent intrapleural injections of the asbestos dust induce in rats more mesotheliomae tht the rare ones in the same and large doses.}, } @article {pmid7580350, year = {1993}, author = {Renke, W and Rosik, E}, title = {Distant health effects of using asbestos in shipyards and in co-operating plants.}, journal = {Bulletin of the Institute of Maritime and Tropical Medicine in Gdynia}, volume = {44-45}, number = {1-4}, pages = {5-11}, pmid = {7580350}, issn = {0324-8542}, mesh = {Adult ; Asbestos/*adverse effects ; Asbestosis/epidemiology ; Bronchitis/epidemiology/etiology ; Chronic Disease ; Female ; Humans ; Incidence ; Longitudinal Studies ; Male ; Neoplasms/epidemiology/etiology ; Occupational Diseases/*epidemiology/etiology ; Poland/epidemiology ; *Ships ; Smoking/adverse effects/epidemiology ; }, abstract = {A survey was conducted during a 15-years period (1981-1994) among a group of workers employed in shipyards and in cooperating plants, who were exposed to asbestos. In a group of 681 people surveyed a growing incidence of asbestosis of the lung was revealed: from 3.9% in 1981 to 17.9% in 1994. Since 1990, 19 persons have been found to have malignant neoplasms, in that number in 9 cases the location of neoplasm was evidently associated with the effects of the asbestos dust (3 mesotheliomas of the pleura and 6 bronchial cancers of the lungs). The smoking habit was probably a contributing factor in the occurrence of these diseases.}, } @article {pmid7458474, year = {1981}, author = {Lewis, RJ and Sisler, GE and Mackenzie, JW}, title = {Diffuse, mixed malignant pleural mesothelioma.}, journal = {The Annals of thoracic surgery}, volume = {31}, number = {1}, pages = {53-60}, doi = {10.1016/s0003-4975(10)61316-1}, pmid = {7458474}, issn = {0003-4975}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Asbestosis/diagnosis ; Female ; Humans ; Male ; Mesothelioma/*diagnosis/etiology/therapy ; Methods ; Middle Aged ; Pleural Effusion/cytology ; Pleural Neoplasms/*diagnosis/etiology/therapy ; Prognosis ; Thoracoscopy ; }, abstract = {Forty-six patients with diffuse, mixed malignant pleural mesothelioma were treated between January, 1970, and May, 1979. All had a history of exposure to asbestos. The diagnosis was established by thoracentesis in 3 patients, thoracoscopy in 28, thoracotomy in 5, and minithoracotomy in 9. Mediastinoscopy was performed in 31 patients and bronchoscopy in 32. Mediastinoscopy was positive in only 1 patient, and in no patient was bronchoscopy positive. Ten patients received no definitive therapy and survived an average of 9.1 months (1 lived for 16 months). Thirty-one patients received chemotherapy and survived an average of 9.6 months, the 2 longest survivors each lived for 24 months. Five patients appeared to have early disease and therefore underwent thoracotomy. In only 2 of these patients did resection of all gross disease appear possible. One patient with incomplete removal is still alive after 9 months. The other 4 are all dead, having survived an average of only 6.75 months. We believe that pleural mesothelioma should be considered an unresectable neoplasm because of its multicentric origin and its diffusely invasive nature, and that attempts at partial or complete resection are not indicated. Until prospective, controlled studies demonstrate otherwise, patients with diffuse, mixed malignant mesothelioma should have the most benign surgical procedure necessary to establish a diagnosis.}, } @article {pmid7448712, year = {1980}, author = {Selikoff, IJ and Hammond, EC and Seidman, H}, title = {Latency of asbestos disease among insulation workers in the United States and Canada.}, journal = {Cancer}, volume = {46}, number = {12}, pages = {2736-2740}, doi = {10.1002/1097-0142(19801215)46:12<2736::aid-cncr2820461233>3.0.co;2-l}, pmid = {7448712}, issn = {0008-543X}, support = {ES00928/ES/NIEHS NIH HHS/United States ; OH00320/OH/NIOSH CDC HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Asbestos/adverse effects ; Asbestosis/*epidemiology/mortality ; Canada ; Humans ; Lung Neoplasms/etiology ; Male ; Mesothelioma/etiology ; Middle Aged ; Occupational Diseases/*epidemiology ; Peritoneal Neoplasms/etiology ; Pleural Neoplasms/etiology ; Time Factors ; United States ; }, abstract = {Two thousand two hundred seventy-one deaths were recorded among 17,800 asbestos insulation workers observed from January 1, 1967-December 31, 1976. There was little increase in cancer deaths or of asbestosis in less than 15-19 years from onset of employment. In general, though, the period of clinical latency was 2-4 decades or more and there were important differences among the several asbestos-associated diseases. Lung cancer peaked at about 30-35 years from onset and asbestosis at 40-45 years. Each tended to decline in incidence afterwards. Pleural and peritoneal mesothelioma reached their highest incidence later than lung cancer, but the incidence did not decline. In studies of effects of asbestos exposure, it appears advantageous to observe for at least 35-40 years or more from onset of exposure and to analyze the experience in duration-from-onset categories. If this is not possible, only the very limited early effects will be identified and the full import of the exposure may not be appreciated.}, } @article {pmid7472312, year = {1980}, author = {Kahn, EI and Rohl, A and Barrett, EW and Suzuki, Y}, title = {Primary pericardial mesothelioma following exposure to asbestos.}, journal = {Environmental research}, volume = {23}, number = {2}, pages = {270-281}, doi = {10.1016/0013-9351(80)90061-4}, pmid = {7472312}, issn = {0013-9351}, mesh = {Asbestos/*adverse effects ; Heart Neoplasms/*etiology/pathology ; Humans ; Male ; Mesothelioma/*etiology/pathology ; Pericardium ; }, } @article {pmid7471040, year = {1980}, author = {Tagnon, I and Blot, WJ and Stroube, RB and Day, NE and Morris, LE and Peace, BB and Fraumeni, JF}, title = {Mesothelioma associated with the shipbuilding industry in coastal Virginia.}, journal = {Cancer research}, volume = {40}, number = {11}, pages = {3875-3879}, pmid = {7471040}, issn = {0008-5472}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Humans ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Occupational Diseases/*epidemiology ; Ships ; Smoking ; Virginia ; }, abstract = {A case-control study was undertaken to clarify reasons for a four-fold increased incidence of mesothelioma discovered among white males in coastal Tidewater, Va., from 1972 to 1978. Sixty-one cases were identified. Interviews with next of kin revealed that the excess was linked to employment in area shipyards. Three-fourths of the cases had been employed in the shipbuilding industry, nearly all beginning employment prior to 1950. Most were career employees, but an increased risk was also found among those who worked only temporarily, mainly during World War II, and were reportedly exposed to asbestos. More of the cases than controls were pipecoverers or pipefitters, but cases were reported to work in a variety of shipyard trades. Few of the mesothelioma cases were heavy smokers, a trend that may be related in part to the competing risks for fatal diseases caused by the interactions of smoking and asbestos exposure. Information obtained by interview for five of the six white females diagnosed with mesothelioma revealed that the husband of four had been employed in the shipbuilding industry.}, } @article {pmid7459217, year = {1980}, author = {Brown, DG and Wagner, JC and Wagner, MM}, title = {Failure to demonstrate tumour-associated transplantation antigens on asbestos-induced mesotheliomas in rats.}, journal = {British journal of cancer}, volume = {42}, number = {5}, pages = {797-801}, pmid = {7459217}, issn = {0007-0920}, mesh = {Animals ; Antigens, Neoplasm/*analysis ; *Asbestos ; Female ; Graft Survival ; Histocompatibility Antigens/*analysis ; Male ; Mesothelioma/etiology/*immunology ; Neoplasm Transplantation ; Neoplasms, Experimental/etiology/immunology ; Rats ; Rats, Inbred Strains ; Transplantation, Isogeneic ; }, } @article {pmid7448133, year = {1980}, author = {Ophus, EM and Mowé, G and Osen, KK and Gylseth, B}, title = {Scanning electron microscopy and x-ray microanalysis of mineral deposits in lungs of a patient with pleural mesothelioma.}, journal = {British journal of industrial medicine}, volume = {37}, number = {4}, pages = {375-381}, pmid = {7448133}, issn = {0007-1072}, mesh = {Adult ; Asbestos/analysis ; Electron Probe Microanalysis ; Humans ; Lung/analysis/*ultrastructure ; Male ; Mesothelioma/analysis/*ultrastructure ; Microscopy, Electron, Scanning ; Occupational Diseases/metabolism/*pathology ; Pleural Neoplasms/analysis/*ultrastructure ; }, abstract = {Scanning electron microscopy of lung tissue, ashed at low temperature, and obtained from an insulation worker who had died of pleural mesothelioma, showed the presence of numerous inorganic particles and fibres. A regional variation in fibre concentration in different tissue samples was found, and the size distribution of naked fibres and asbestos bodies was determined. By energy dispersive x-ray microanalysis the fibres were identified mainly as amphibole asbestos. This method also showed the presence of particles containing titanium and of fragments of diatom shells. Despite a mean concentration of 33 x 10(6) fibres per gram of dry tissue no significant lung fibrosis was found.}, } @article {pmid7465255, year = {1980}, author = {Griffiths, MH and Riddell, RJ and Xipell, JM}, title = {Malignant mesothelioma: a review of 35 cases with diagnosis and prognosis.}, journal = {Pathology}, volume = {12}, number = {4}, pages = {591-603}, doi = {10.3109/00313028009086812}, pmid = {7465255}, issn = {0031-3025}, mesh = {Adult ; Aged ; Female ; Heart Neoplasms/diagnosis/pathology ; Humans ; Male ; Mesothelioma/*diagnosis/pathology ; Middle Aged ; Peritoneal Neoplasms/diagnosis/pathology ; Pleural Neoplasms/diagnosis/pathology ; Prognosis ; }, abstract = {Twenty-five men and 10 women with malignant mesothelioma seen at the Austin Hospital between 1965 and 1978 were reviewed. The patients ranged in age from 34 to 79 yr. Prognosis was poor but was somewhat better for patients with epithelioid tumours than for patients with fibrous mesotheliomas and biphasic tumours. A history of occupational exposure to asbestos was obtained in the majority of patients, the latent period being from 18 to 52 yr. Ten patients had no history of asbestos exposure. The pathological diagnosis was established on tissue obtained at open biopsy in 22 cases and at post mortem in 11. Needle biopsy provided a diagnosis in only 2 cases. Cytology suggested a diagnosis of mesothelioma in 1 case. Gross pathology in general conformed with a diffuse confluent-nodular serosal tumor. A right sided preponderance was found in pleural tumours, and metastases were found rather more frequently than is usually reported. Histological features were distinctive in the majority of cases provided that sufficient material was examined. Recognition of coexisting patterns was often more helpful in making the diagnosis than any one single feature. Histochemical reactions are useful in distinguishing mesothelioma from mucin-secreting adenocarcinoma. In a majority of cases the histology and histochemistry were not characteristic and the diagnosis depended on the clinical features and the absence of another primary source of tumour.}, } @article {pmid7442145, year = {1980}, author = {McCullagh, SF}, title = {Amosite as a cause of lung cancer and mesothelioma in humans.}, journal = {The Journal of the Society of Occupational Medicine}, volume = {30}, number = {4}, pages = {153-156}, doi = {10.1093/occmed/30.4.153}, pmid = {7442145}, issn = {0301-0023}, mesh = {Asbestos/*adverse effects ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; }, } @article {pmid7445156, year = {1980}, author = {Christensen, JB and Rehfeld, E}, title = {[Mesothelioma in a gardener briefly exposed to asbestos].}, journal = {Ugeskrift for laeger}, volume = {142}, number = {38}, pages = {2510}, pmid = {7445156}, issn = {0041-5782}, mesh = {Asbestos/*adverse effects ; Humans ; Male ; Mesothelioma/*chemically induced ; Middle Aged ; Occupational Diseases/chemically induced ; Pleural Neoplasms/*chemically induced ; }, } @article {pmid7463518, year = {1980}, author = {Huuskonen, MS}, title = {Asbestos and cancer in Finland.}, journal = {Journal of toxicology and environmental health}, volume = {6}, number = {5-6}, pages = {1261-1265}, doi = {10.1080/15287398009529945}, pmid = {7463518}, issn = {0098-4108}, mesh = {Asbestos/*adverse effects ; Finland ; Humans ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Neoplasms/*etiology ; Occupational Diseases/etiology ; Sputum/cytology ; }, abstract = {Cancer mortality of men with diagnosed asbestosis was studied in Finland. Of the 174 men registered as having asbestosis, 56 had died before 1977, whereas the number of expected deaths based on the Finnish male population was only 23.4. The respective figures for lung cancer were 19 observed and 2.1 expected. The mean age of these 19 lung cancer patients was 57.8 yr, and lung cancer was the cause of death (underlying cause) in 35% of all diseased men with asbestosis. The proportion of lung cancer mortality from all deaths among Finnish men 55-64 yr old is 10.8%, which is clearly lower than that among the men with asbestosis. No excess of other malignancies was found in Finland among workers with asbestosis.}, } @article {pmid7463500, year = {1980}, author = {Norseth, T}, title = {Asbestos and metals as carcinogens.}, journal = {Journal of toxicology and environmental health}, volume = {6}, number = {5-6}, pages = {1021-1028}, doi = {10.1080/15287398009529924}, pmid = {7463500}, issn = {0098-4108}, mesh = {Animals ; Arsenic/toxicity ; Asbestos/*toxicity ; *Carcinogens ; Chromium/toxicity ; Chromosome Aberrations ; Glucose/metabolism ; Hemolysis/drug effects ; Humans ; Lung Neoplasms/etiology ; Metals/*toxicity ; Nickel/toxicity ; }, abstract = {Increased incidences of lung carcinoma and pleural mesothelioma in humans exposed to asbestos have been irrefutably established. Different forms of asbestos may have different tumorigenic activities, depending on surface properties, durability, and size of the fibers. A number of metals, such as nickel, chromium, and arsenic, are known to be carcinogenic to humans; for beryllium and cadmium the epidemiologic evidence is less extensive. All these metals also induce genetic toxicity in vitro. For chromium the molecular mechanism of metal tumorigenesis has been extensively investigated; the hexavalent form is generally a much more potent mutagen than is chromium (III). Solubility seems to be necessary for the genotoxicity of nickel. At present it cannot be concluded that all metals act by the same carcinogenic mechanism, even though direct modification of DNA seems to be the common experimental finding.}, } @article {pmid7447497, year = {1980}, author = {Sheers, G and Coles, RM}, title = {Mesothelioma risks in a naval dockyard.}, journal = {Archives of environmental health}, volume = {35}, number = {5}, pages = {276-282}, pmid = {7447497}, issn = {0003-9896}, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Asbestos/poisoning ; Dust ; Humans ; Male ; Mesothelioma/*etiology ; Middle Aged ; Occupational Diseases/*etiology ; Peritoneal Neoplasms/*etiology ; Pleural Neoplasms/*etiology ; Risk ; Time Factors ; }, abstract = {There have been 108 deaths from mesothelioma of the pleura or peritoneum in Plymouth and the immediate neighborhood as of mid-1978. Ninety-six deaths have been associated with work at the Devonport Dockyard, 53 of which represented men employed at the dockyard in 1966. Occupational mesothelioma rates were similar to those recorded in London asbestos textile workers. Above average rates in this study were observed in laggers, boilermakers, painters, welders and burners, and shipwrights. In addition to mesothelioma in other men with neighborhood exposure at work, cases have occurred in men whose only exposure has been to the environment within the walls of the dockyard, outside ships and workshops where asbestos has been handled. No case has been seen in indoor office workers. There is no evidence of any increase in risk to the population of Plymouth outside the dockyard.}, } @article {pmid7444823, year = {1980}, author = {Yazicioglu, S and Ilçayto, R and Balci, K and Sayli, BS and Yorulmaz, B}, title = {Pleural calcification, pleural mesotheliomas, and bronchial cancers caused by tremolite dust.}, journal = {Thorax}, volume = {35}, number = {8}, pages = {564-569}, pmid = {7444823}, issn = {0040-6376}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Calcinosis/*epidemiology ; Carcinoma, Bronchogenic/*epidemiology ; Environmental Exposure ; Female ; Humans ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Paint/adverse effects ; Pleural Diseases/*epidemiology ; Pleural Neoplasms/*epidemiology ; Pulmonary Fibrosis/epidemiology ; Turkey ; }, abstract = {Around the town of Cermik in south-east Turkey there are many deposits of asbestiform minerals, some of which are used to make whitewash or stucco. A sample of 7000 of the population revealed 461 (6.5%) with pleural thickening and calcification, of whom 103 (1.47% of the total) had evidence of interstitial pulmonary fibrosis. Forty-one patients with respiratory cancer were admitted to the Diyarbakir Chest Hospital from around Cermik and from a comparable area of equal population (but without asbestos deposits) in 1977-8. Of these 23 were mesotheliomas, 22 coming from around Cermik. In addition, 11 of the 18 primary bronchial cancers came from around Cermik. A similar excess of mesothelioma and bronchial cancer had been admitted from the Cermik area in previous years. The whitewash or stucco material has been shown to contain fibrous tremolite and non-fibrous antigorite/lizardite, chlorite, and talc. A lung biopsy of a patient from Cermik contained large numbers of tremolite fibres, both free and forming asbestos bodies. There were only occasional chrysotile fibres.}, } @article {pmid7444822, year = {1980}, author = {Elmes, PC}, title = {Mesotheliomas, minerals, and man-made mineral fibres.}, journal = {Thorax}, volume = {35}, number = {8}, pages = {561-563}, pmid = {7444822}, issn = {0040-6376}, mesh = {Air Pollutants ; Asbestos/*adverse effects ; Environmental Exposure ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Mining ; Occupational Diseases/etiology ; Pleural Neoplasms/etiology ; Time Factors ; }, } @article {pmid7441085, year = {1980}, author = {Smith, WE and Hubert, DD and Sobel, HJ and Peters, ET and Doerfler, TE}, title = {Health of experimental animals drinking water with and without amosite asbestos and other mineral particles.}, journal = {Journal of environmental pathology and toxicology}, volume = {3}, number = {5-6}, pages = {277-300}, pmid = {7441085}, issn = {0146-4779}, mesh = {Animals ; Asbestos/*toxicity ; Body Weight/drug effects ; Cricetinae ; Female ; Male ; Mesocricetus ; Minerals/*toxicity ; Neoplasms, Experimental/chemically induced/pathology ; Particle Size ; *Water Supply ; }, abstract = {In view of diseases associated with inhalation of asbestos fibers, interest attaches to the question of whether risks are presented by ingestion of asbestos or mineralogically related fibrous-shaped particles reported in drinking water supplies. Experimental animals (hamsters) were maintained on filtered drinking water with and without addition of mineral particles. A peritoneal mesothelioma, pulmonary carcinoma and two early squamous cell carcinomas of the forestomach were found in hamsters so exposed to a preparation of amosite asbestos. These tumors could not be specifically attributed to amosite, but they show that hamsters of the strain used were capable of developing tumors of particular interest in this experiment. No deleterious health effects and no tumors related to treatment were found in hamsters exposed to milled taconite ore containing fibrous-shaped particles of cummingtonite/grunerite, mineralogically related to amosite but in shorter lengths more comparable in size to fibers associated with drinking water supplies.}, } @article {pmid2176805, year = {1990}, author = {Piolatto, G and Negri, E and La Vecchia, C and Pira, E and Decarli, A and Peto, J}, title = {An update of cancer mortality among chrysotile asbestos miners in Balangero, northern Italy.}, journal = {British journal of industrial medicine}, volume = {47}, number = {12}, pages = {810-814}, pmid = {2176805}, issn = {0007-1072}, mesh = {Alcohol Drinking/adverse effects ; Asbestos/*adverse effects ; Asbestos, Serpentine ; Cause of Death ; Cohort Studies ; Humans ; Italy/epidemiology ; Laryngeal Neoplasms/etiology/mortality ; Male ; *Mining ; Mouth Neoplasms/mortality ; Neoplasms/*mortality ; Occupational Diseases/*mortality ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/mortality ; Time Factors ; }, abstract = {The mortality experience of a cohort of chrysotile miners employed since 1946 in Balangero, northern Italy was updated to the end of 1987 giving a total of 427 deaths out of 27,010 man-years at risk. A substantial excess mortality for all causes (standardised mortality ratio (SMR) = 149) was found, mainly because of high rates for some alcohol related deaths (hepatic cirrhosis, accidents). For mortality from cancer, however, the number of observed deaths (82) was close to that expected (76.2). The SMR was raised for oral cancer (SMR 231 based on six deaths), cancer of the larynx (SMR 267 based on eight deaths), and pleura (SMR 667 based on two deaths), although the excess only reached statistical significance for cancer of the larynx. Rates were not increased for lung, stomach, or any other type of cancer. No consistent association was seen with duration or cumulative dust exposure (fibre-years) for oral cancer, but the greatest risks for laryngeal and pleural cancer were in the highest category of duration and degree of exposure to fibres. Although part of the excess mortality from laryngeal cancer is probably attributable to high alcohol consumption in this group of workers, the data suggest that exposure to chrysotile asbestos (or to the fibre balangeroite that accounts for 0.2-0.5% of total mass in the mine) is associated with some, however moderate, excess risk of laryngeal cancer and pleural mesothelioma. The absence of excess mortality from lung cancer in this cohort is difficult to interpret.}, } @article {pmid2151850, year = {1990}, author = {Gruber, UF}, title = {Asbestos-related benign disease and cancer: symptoms and treatment.}, journal = {Anti-cancer drugs}, volume = {1}, number = {2}, pages = {187-197}, doi = {10.1097/00001813-199012000-00012}, pmid = {2151850}, issn = {0959-4973}, mesh = {Aged ; Asbestos/*adverse effects ; Asbestosis/complications/epidemiology/*etiology ; Callosities/etiology ; Humans ; Lung Neoplasms/epidemiology/etiology ; Male ; Mesothelioma/epidemiology/etiology ; Middle Aged ; Neoplasms/epidemiology/*etiology ; Warts/etiology ; }, abstract = {Long lasting occupational exposure to asbestos dust may cause skin corns, benign pleural effusion, hyaline plaques of the parietal pleura, diffuse thickening of the pulmonary pleura, and asbestosis, i.e. diffuse interstitial pulmonary fibrosis. Malignant disorders include lung cancer and mesothelioma of the pleura, peritoneum and pericardium. In general, many years elapse from first exposure to the appearance of symptoms. Almost all these diseases are the result of dusty working conditions more than 20 years ago. In spite of the fact that the general public is invariably exposed to small amounts of the material, asbestos is not a public health problem. Even living in a building containing sprayed asbestos is calculated to produce a lifetime risk of death which is negligible. There is no evidence to indicate that ingested asbestos fibres represent a major health problem.}, } @article {pmid2151326, year = {1990}, author = {Bruno, C and De Santis, M and Comba, P and Bagnato, R}, title = {[Mortality in malignant tumors of the peritoneum in Italy: search for correlations with exposure to asbestos].}, journal = {Epidemiologia e prevenzione}, volume = {12}, number = {45}, pages = {39-47}, pmid = {2151326}, issn = {1120-9763}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Female ; Humans ; Italy ; Male ; Mesothelioma/etiology/*mortality ; Middle Aged ; Occupational Diseases/*mortality ; Peritoneal Neoplasms/etiology/*mortality ; }, abstract = {In the years 1981-85, 2438 malignant neoplasms of peritoneum occurred in Italy: the crude mortality rate was 0.86 X 10(-5) per year. The standardized mortality rates of Italian provinces ranged from 0.20 to 1.86 X 10(-5) per year. Some degree of misclassification can affect the ascertainment of peritoneal tumors as a death cause. In some of the Provinces with the highest mortality rates dockyards or asbestos-cement industries are located (e.g. Genova, La Spezia; Alessandria); in other Provinces the presence of industries involving an important use of asbestos could not be ruled out.}, } @article {pmid2149468, year = {1990}, author = {Skov, T and Mikkelsen, S and Svane, O and Lynge, E}, title = {Reporting of occupational cancer in Denmark.}, journal = {Scandinavian journal of work, environment & health}, volume = {16}, number = {6}, pages = {401-405}, doi = {10.5271/sjweh.1770}, pmid = {2149468}, issn = {0355-3140}, mesh = {Adenocarcinoma/*epidemiology ; Adult ; Aged ; Denmark/epidemiology ; Female ; Humans ; Male ; Medical Records/standards ; Mesothelioma/*epidemiology ; Middle Aged ; National Health Programs ; Nose Neoplasms/*epidemiology ; Occupational Diseases/*epidemiology ; Occupational Exposure ; Occupational Medicine/legislation & jurisprudence/standards ; Pleural Neoplasms/*epidemiology ; Workers' Compensation ; }, abstract = {Many patients with occupational diseases fail to obtain compensation because their disease is not recognized as occupational and reported to the authorities. The present study examined the reporting of pleural mesotheliomas and sinonasal adenocarcinomas--cancers with well-known associations with occupational exposures to asbestos and wood dust--in Denmark in 1983-1987. The estimated underreporting was around 50%. Examination of the medical records of patients who had not been reported in 1986-1987 revealed that in most cases the medical records did not contain sufficiently detailed information about occupational exposures. It was recommended that a formal screening interview be carried out whenever a diagnosis is made of a potential occupational cancer. Medical associations may play a major role by issuing guidelines addressing occupational diseases within the fields of their expertise.}, } @article {pmid2097820, year = {1990}, author = {Finkelstein, MM}, title = {The exposure-response relationship for mesothelioma among asbestos-cement factory workers.}, journal = {Toxicology and industrial health}, volume = {6}, number = {6}, pages = {623-627}, pmid = {2097820}, issn = {0748-2337}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Australia/epidemiology ; Case-Control Studies ; Humans ; Male ; Mesothelioma/epidemiology/*etiology/mortality ; Middle Aged ; Occupational Exposure ; Ontario/epidemiology ; Peritoneal Neoplasms/epidemiology/*etiology/mortality ; Pleural Neoplasms/epidemiology/*etiology/mortality ; Risk ; Time Factors ; }, abstract = {Forty-five deaths from mesothelioma have occurred among production workers in an asbestos-cement factory. This analysis examines the fit of the cubic residence time model to the incidence of mesothelioma using a case-control method proposed by de Klerk and colleagues. The cubic residence time model was found to provide a good description of the data.}, } @article {pmid2256205, year = {1990}, author = {Lange, P and Balk-Møller, S}, title = {[Asbestos-induced lung diseases].}, journal = {Ugeskrift for laeger}, volume = {152}, number = {47}, pages = {3520-3524}, pmid = {2256205}, issn = {0041-5782}, mesh = {Asbestosis/*etiology ; Carcinoma, Bronchogenic/*chemically induced ; Denmark ; Humans ; Lung Diseases/*chemically induced ; Lung Neoplasms/*chemically induced ; Mesothelioma/etiology ; Occupational Diseases/*etiology ; Occupational Exposure ; Pleural Diseases/etiology ; Pleural Effusion/etiology ; Pleural Neoplasms/*chemically induced ; }, abstract = {Asbestos fibres have potent cancerogenic and fibrogenic properties and may lead to development of cancer and fibrosis in the lung parenchyma and pleura. The Danish Ministry of Employment has established rules which should prevent development of disease when working with asbestos in future but, on account of the very long latent period between exposure and development of asbestos-related disease, these conditions will still occur during the next 30-40 years. Primarily, the more benign pleural plaques will be concerned but serious disease such as bronchial carcinoma and pleural mesothelioma will occur in the future. When patients are encountered who present symptoms or objective/paraclinical findings which are compatible with disease produced by asbestos, it is important to remember that exposure to asbestos may be many decades ago and, particularly where the malignant conditions are concerned, exposure need not have been particularly massive or prolonged. All cases where asbestos-related disease is suspected should be notified to the insurance administration.}, } @article {pmid2233438, year = {1990}, author = {Nielsen, C and Hansen, IM}, title = {Sarcomatous mesothelioma of the pleura with cerebral metastases.}, journal = {The Medical journal of Australia}, volume = {153}, number = {10}, pages = {625-626}, doi = {10.5694/j.1326-5377.1990.tb126277.x}, pmid = {2233438}, issn = {0025-729X}, mesh = {Adult ; Biopsy ; Brain Neoplasms/diagnostic imaging/epidemiology/*secondary ; Female ; Humans ; Incidence ; Mesothelioma/*complications/diagnostic imaging/pathology ; Pleural Neoplasms/*complications/diagnostic imaging/pathology ; Tomography, X-Ray Computed ; }, abstract = {A case of sarcomatous pleural mesothelioma in a 22-year-old woman is presented. There was no history of occupational exposure to asbestos. Twenty months after the first symptoms occurred the patient noticed weakness in the right arm. A computed tomography scan of the brain showed multiple metastases. The patient died 10 days later.}, } @article {pmid2247791, year = {1990}, author = {Reid, G and Kielkowski, D and Steyn, SD and Botha, K}, title = {Mortality of an asbestos-exposed birth cohort. A pilot study.}, journal = {South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde}, volume = {78}, number = {10}, pages = {584-586}, pmid = {2247791}, issn = {0256-9574}, mesh = {Aged ; Asbestos/*adverse effects ; Cohort Studies ; Environmental Exposure ; Female ; Humans ; Male ; Mesothelioma/*mortality ; Middle Aged ; Pilot Projects ; South Africa/epidemiology ; }, abstract = {A pilot study on the health effects of environmental exposure to asbestos (in particular the development of mesothelioma) is almost complete. This is a record linkage study, using birth and death records as the primary sources of data. The vital status and, if applicable, the cause of death was examined for each of the 1227 members of the 'pilot' cohort (birth years 1932-1936). Preliminary results are presented. Eighty-seven per cent (399) of the white cohort members have been traced and the vital status of each has been determined. Sixty-six whites have died, 6 from mesothelioma. It is almost impossible to trace the black and coloured cohort members and the main study, covering the years of birth 1917-1936, may have to be restricted to whites.}, } @article {pmid2147399, year = {1990}, author = {Arblaster, L and Hatton, P and Schweiger, MS and Renvoize, ER and Howel, D}, title = {Asbestos diseases and compensation.}, journal = {BMJ (Clinical research ed.)}, volume = {301}, number = {6760}, pages = {1101}, pmid = {2147399}, issn = {0959-8138}, mesh = {Asbestos/*adverse effects ; Female ; Humans ; Male ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; United Kingdom ; *Workers' Compensation ; }, } @article {pmid2274692, year = {1990}, author = {Langer, AM and Nolan, RP}, title = {Pleural mesothelioma after asbestos exposure.}, journal = {Respiratory medicine}, volume = {84}, number = {6}, pages = {509-510}, doi = {10.1016/s0954-6111(08)80119-9}, pmid = {2274692}, issn = {0954-6111}, mesh = {Asbestos/*adverse effects ; Construction Materials/*adverse effects ; Female ; Humans ; Mesothelioma/*etiology ; Occupational Exposure/adverse effects ; Pleural Neoplasms/*etiology ; }, } @article {pmid2245193, year = {1990}, author = {Arblaster, L and Renvoize, E and Hatton, P and Schweiger, M}, title = {Asbestos: a chronology of its origins and health effects.}, journal = {British journal of industrial medicine}, volume = {47}, number = {11}, pages = {790}, doi = {10.1136/oem.47.11.790}, pmid = {2245193}, issn = {0007-1072}, mesh = {Asbestosis/*history ; History, 20th Century ; Humans ; Lung Neoplasms/history ; Male ; Mesothelioma/history ; Occupational Diseases/*history ; }, } @article {pmid2245188, year = {1990}, author = {Meijers, JM and Planteydt, HT and Slangen, JJ and Swaen, GM and van Vliet, C and Sturmans, F}, title = {Trends and geographical patterns of pleural mesotheliomas in the Netherlands 1970-87.}, journal = {British journal of industrial medicine}, volume = {47}, number = {11}, pages = {775-781}, pmid = {2245188}, issn = {0007-1072}, mesh = {Adult ; Age Factors ; Aged ; Asbestos/adverse effects ; Demography ; Female ; Humans ; Male ; Mesothelioma/*epidemiology/etiology/mortality ; Middle Aged ; Netherlands/epidemiology ; Occupational Diseases/*epidemiology ; Pleural Neoplasms/*epidemiology/etiology/mortality ; Sex Factors ; }, abstract = {The sex and age related trends and geographical distribution of asbestos related mortality from pleural mesothelioma in the Netherlands between 1970 and 1987 were investigated. Deaths from pleural malignancies recorded by the Dutch Central Bureau of Statistics (CBS) were used and death rates were age adjusted per year by the indirect method. Standardised mortality ratios (SMRs) were computed for 43 regions over the period 1979-86. For men, total mortality increased from 10.8 per million in the period 1970-8 to 20.9 per million during 1979-87. The highest mortality occurred in the group aged between 65 and 74 with 147.7 per million in 1987. The death rate for the group aged between 55 and 64 was 96.5 per million in 1987. For women, total death rates for pleural mesothelioma showed a moderate increase from 2.5 per million in the period 1970-8 to 3.6 per million during 1979-87. The highest mortality occurred in the group aged over 65, fluctuating around 10-15 per million. For men and women under 45 mortality was very low and presented no upward trend. The geographical distribution over the country for the period 1979-86 showed a pattern with a clear concentration of deaths from mesothelioma in men, in conurbations with many harbours, shipyards, and heavy industry near the river mouths and along the North Sea Coast.}, } @article {pmid2241560, year = {1990}, author = {Asensio, JA and Goldblatt, P and Thomford, NR}, title = {Primary malignant peritoneal mesothelioma. A report of seven cases and a review of the literature.}, journal = {Archives of surgery (Chicago, Ill. : 1960)}, volume = {125}, number = {11}, pages = {1477-1481}, doi = {10.1001/archsurg.1990.01410230071012}, pmid = {2241560}, issn = {0004-0010}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; *Mesothelioma/diagnosis/pathology/surgery ; Middle Aged ; *Peritoneal Neoplasms/diagnosis/pathology/surgery ; }, abstract = {Mesothelioma of the peritoneum is a rare malignant neoplasm easily mistaken by both surgeon and pathologist for one of the more common neoplasms of the abdomen. Review of our records from metropolitan-area hospitals for the past 15 years identified seven patients with primary peritoneal mesotheliomas. Their diagnosis, management, and survival is analyzed. We report a case of an extended survivor (7 years) and one of a long-term survivor (15 years), as well as what we believe to be the only case in the literature presenting with a coexistent malignant neoplasm. Prevention of this commonly fatal neoplasm is linked to avoiding occupational exposure to asbestos; long-term survival for a few patients may be achieved with correct identification of the neoplasm and aggressive management. This report includes a review of the literature.}, } @article {pmid2173948, year = {1990}, author = {Albin, M and Johansson, L and Pooley, FD and Jakobsson, K and Attewell, R and Mitha, R}, title = {Mineral fibres, fibrosis, and asbestos bodies in lung tissue from deceased asbestos cement workers.}, journal = {British journal of industrial medicine}, volume = {47}, number = {11}, pages = {767-774}, pmid = {2173948}, issn = {0007-1072}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Asbestos, Amphibole ; Asbestos, Serpentine ; *Construction Materials ; Humans ; Lung/*ultrastructure ; Mesothelioma/etiology/*pathology ; Middle Aged ; Occupational Diseases/etiology/*pathology ; Pulmonary Fibrosis/etiology/*pathology ; Silicic Acid/adverse effects ; Silicon Dioxide/adverse effects ; }, abstract = {Lung tissue from 76 deceased asbestos cement workers (seven with mesothelioma) exposed to chrysotile asbestos and small amounts of amphiboles, has been studied by transmission electron microscopy, together with lung tissue from 96 controls. The exposed workers with mesothelioma had a significantly higher total content of asbestos fibre in the lungs than those without mesothelioma, who in turn, had higher concentrations than the controls (medians 189, 50, and 29 x 10(6) fibres/g (f/g]. Chrysotile was the major type of fibre. The differences were most pronounced for the amphibole fibres (62, 4.7, and 0.15 f/g), especially crocidolite (54, 1.8 and less than 0.001 f/g), but were evident also for tremolite (2.9, less than 0.001, and less than 0.001 f/g) and anthophyllite (1.7, less than 0.001, and less than 0.001 f/g). For amosite, there was no statistically significant difference between lungs from workers with and without mesothelioma; the lungs of workers had, however, higher concentrations than the controls. Strong correlations were found between duration of exposure and content of amphibole fibres in the lungs. Asbestos bodies, counted by light microscopy, were significantly correlated with the amphibole but not with the chrysotile contents. Fibrosis was correlated with the tremolite but not the chrysotile content in lungs from both exposed workers and controls. Overall, similar results were obtained using fibre counts and estimates of mass.}, } @article {pmid2120965, year = {1990}, author = {Kawashima, A and Libshitz, HI}, title = {Malignant pleural mesothelioma: CT manifestations in 50 cases.}, journal = {AJR. American journal of roentgenology}, volume = {155}, number = {5}, pages = {965-969}, doi = {10.2214/ajr.155.5.2120965}, pmid = {2120965}, issn = {0361-803X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Lymphatic Metastasis ; Male ; Mesothelioma/*diagnostic imaging/secondary ; Middle Aged ; Neoplasm Invasiveness ; Pleural Neoplasms/*diagnostic imaging ; *Tomography, X-Ray Computed ; }, abstract = {Malignant pleural mesothelioma, a rare and usually fatal neoplasm that is associated with asbestos exposure, is being encountered with increasing frequency. Pretreatment CT findings from 50 patients with malignant pleural mesothelioma are illustrated. Pleural thickening was found in 46 (92%) of the 50 patients, thickening of the pleural surfaces of the interlobar fissures in 43 (86%), pleural calcifications in 10 (20%), and pleural effusions in 37 (74%). The volume of the involved hemithorax varied appreciably. Contractions of the involved hemithorax was noted in 21 (42%) of 50 patients and contralateral mediastinal shift in seven (14%). Disease beyond the parietal pleura was found in the chest wall (nine patients), mediastinum, lymph nodes, and diaphragm.}, } @article {pmid2173188, year = {1990}, author = {Otte, KE and Sigsgaard, TI and Kjaerulff, J}, title = {[Massive exposure to asbestos and malignant mesothelioma, familial accumulation].}, journal = {Ugeskrift for laeger}, volume = {152}, number = {41}, pages = {3013-3014}, pmid = {2173188}, issn = {0041-5782}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Asbestos, Amosite ; Environmental Exposure ; Female ; Humans ; Male ; Mesothelioma/etiology/*genetics ; Middle Aged ; Pleural Neoplasms/etiology/*genetics ; }, abstract = {In a family with a remarkable aggregation of malignant mesothelioma the father, mother, and a son all died of the condition, whereas two other sons and a daughter were unaffected. From 1944 to 1961 the family produced a material that was used to fix screws in drilled holes and consisted of amosite, gypsum, and sand. This was produced in the basement of their villa and was described as being a dusty job. The father died in 1984 aged 74, the son in 1985 aged 45, and the mother in 1987 aged 79. It is concluded that there is a high risk of malignant mesothelioma after massive exposure to amosite and the risk and latency period are independent of age during the exposure.}, } @article {pmid2289567, year = {1990}, author = {Martensson, G}, title = {Diagnosing malignant pleural mesothelioma.}, journal = {The European respiratory journal}, volume = {3}, number = {9}, pages = {985-986}, pmid = {2289567}, issn = {0903-1936}, mesh = {Asbestos/adverse effects ; Biopsy ; Carcinoembryonic Antigen/analysis ; Humans ; Mesothelioma/*diagnosis/pathology ; Microscopy, Electron ; Pleura/pathology ; Pleural Neoplasms/*diagnosis/pathology ; }, } @article {pmid2287593, year = {1990}, author = {Kamiya, M and Eimoto, T}, title = {Malignant mesothelioma of the tunica vaginalis.}, journal = {Pathology, research and practice}, volume = {186}, number = {5}, pages = {680-4; discussion 685-6}, doi = {10.1016/S0344-0338(11)80233-5}, pmid = {2287593}, issn = {0344-0338}, mesh = {Adult ; *Epididymis ; Humans ; Immunohistochemistry ; Male ; Mesothelioma/metabolism/*pathology ; *Serous Membrane ; Testicular Neoplasms/metabolism/*pathology ; }, abstract = {A case of a malignant mesothelioma of the tunica vaginalis is presented. The patient with an intrascrotal mass was a 32-year-old Japanese male who had no history of asbestos exposure. The tumor was located on the surface of the right testis and was composed of columnar to polygonal cells with glandular and papillary structures. It showed many mitoses and focal invasion of the tunica albuginea. The tumor cells contained alcian blue- and Hale's colloidal iron-positive, hyaluronidase-digestible materials. Immunohistochemical stains for cytokeratin and vimentin were positive, while those for carcinoembryonic antigen, epithelial membrane antigen, Leu-M1, and factor VIII-related antigen were negative. The systemic examinations revealed no other tumors. Based on these findings the tumor was diagnosed as malignant mesothelioma of the tunica vaginalis. The differential diagnosis is discussed under the histologic, histochemical, and immunohistochemical points of view and the previous literature is reviewed.}, } @article {pmid2281888, year = {1990}, author = {McDonald, JC and Case, BW and Enterline, PE and Henderson, V and McDonald, AD and Plourde, M and Sébastien, P}, title = {Lung dust analysis in the assessment of past exposure of man-made mineral fibre workers.}, journal = {The Annals of occupational hygiene}, volume = {34}, number = {5}, pages = {427-441}, doi = {10.1093/annhyg/34.5.427}, pmid = {2281888}, issn = {0003-4878}, mesh = {Cohort Studies ; Dust/*adverse effects/analysis ; Humans ; Lung Diseases/epidemiology/mortality/*pathology ; Minerals/*adverse effects/analysis ; Occupational Diseases/epidemiology/mortality/*pathology ; United States/epidemiology ; }, abstract = {In the cohort of American MMMF workers reported by ENTERLINE et al. [Ann. occup. Hyg. 31, 625-656 (1987)] autopsies were recorded in 652 (13.5%) of 4840 deaths. Lung tissue samples were sought from all pathologists and obtained in 145 (22.2%), together with similar samples from 124 matched referents. Lung fibre counts by phase contrast microscopy were 60% higher (P less than 0.05) in workers than referents. Electron microscopy (ATEM) also showed more fibres of all kinds--MMMF, asbestos and other--but no convincing excess of any one type. Lung samples of only 26% of workers contained any MMMF, almost all siliceous in nature and in low concentration. There were too few cases of lung cancer (19) for any useful conclusion; however, in the plant with the highest lung cancer SMR (200), and a probable mesothelioma, amosite at greater than 1.0 fibres per micrograms (f micrograms-1) was found in four of six workers but in none of their matched referents. Although our findings contribute little to the interpretation of the results obtained by ENTERLINE et al. they indicate the potential value of tissue analyses in monitoring epidemiological studies of MMMF exposure.}, } @article {pmid2170048, year = {1990}, author = {Brown, RC and Carthew, P and Hoskins, JA and Sara, E and Simpson, CF}, title = {Surface modification can affect the carcinogenicity of asbestos.}, journal = {Carcinogenesis}, volume = {11}, number = {10}, pages = {1883-1885}, doi = {10.1093/carcin/11.10.1883}, pmid = {2170048}, issn = {0143-3334}, mesh = {Animals ; Asbestos/chemistry/pharmacology/*toxicity ; Asbestos, Amosite ; Carcinogenicity Tests ; Carcinogens/*toxicity ; Cell Line ; Cell Survival/drug effects ; Mesothelioma/*chemically induced/pathology ; Rats ; Reference Values ; Surface Properties ; }, abstract = {A sample of amosite asbestos was modified by effectively adding C8 and C18 hydrocarbon chains to the fibre surfaces. The altered fibres interacted less readily with cells in vitro and were less cytotoxic. In whole animals the number of mesotheliomas produced by the C8 material was the same as that with the parent material but the tumours occurred earlier. The C18 derivatized fibre was markedly less active in the production of tumours. This is the first report demonstrating that similar size fibres with differing surfaces have different pathogenic properties.}, } @article {pmid2218349, year = {1990}, author = {Boutin, C and Viallat, JR and Rey, F and Astoul, P and Seitz, B}, title = {[Diagnosis and prognosis of malignant mesothelioma].}, journal = {La Revue du praticien}, volume = {40}, number = {20}, pages = {1846-1850}, pmid = {2218349}, issn = {0035-2640}, mesh = {Adult ; Asbestos/adverse effects ; Biopsy, Needle ; Female ; Humans ; Male ; Mesothelioma/chemically induced/*diagnosis/radiotherapy ; Middle Aged ; Neoplasm Staging ; Pleural Neoplasms/chemically induced/*diagnosis/radiotherapy ; Prognosis ; Thoracoscopy ; }, abstract = {The early diagnosis of mesothelioma rests on very common clinical evidence, including pleuritis of recent onset, history of contact with asbestos, chest pain, often moderate loss of weight and slight changes in old pleural fluid cytology, 24% for Adams' needle biopsy and 93% for thoracoscopy, where the only negative results are obtained in patients with adhesive pleuritis. Prognosis depends on several factors, the most favourable ones being the histological type of the lesion (epithelial or mixed), the fact that it is limited to the parietal or diaphragmatic pleural and, on the patient's side and accessorily: female sex, lack of exposure to asbestos, age under 50, good general condition and absence of chest pain.}, } @article {pmid2218348, year = {1990}, author = {Viallat, JR and Farisse, P and Rey, F and Boutin, C}, title = {[Epidemiology and etiology of mesothelioma].}, journal = {La Revue du praticien}, volume = {40}, number = {20}, pages = {1842-1845}, pmid = {2218348}, issn = {0035-2640}, mesh = {Asbestos/*adverse effects ; Dose-Response Relationship, Drug ; Female ; Humans ; Male ; Mesothelioma/chemically induced/*epidemiology/etiology ; Pleural Neoplasms/chemically induced/*epidemiology/etiology ; Risk Factors ; }, abstract = {The early diagnosis of mesothelioma rests on very common clinical evidence, including pleuritis of recent onset, history of contact with asbestos chest pain, often moderate loss of weight and slight changes in old pleural images. The sensitivity of formal diagnostic examinations is 23 p. 100 for pleural fluid cytology, 24 p. 100 Adams' needle biopsy and 93 p. 100 for thoracoscopy, where the only negative results are obtained in patients with adhesive pleuritis. Prognosis depends on several factors, the most favourable ones being the histological type of the lesion (epithelial or mixed), the fact that it is limited to the parietal or diaphragmatic pleura and, on the patient's side and accessorily: female sex, lack of exposure to asbestos, age under 50, good general condition and absence of chest pain.}, } @article {pmid2218345, year = {1990}, author = {Jaurand, MC and Bernaudin, JF and Bignon, J}, title = {[The mesothelial cells].}, journal = {La Revue du praticien}, volume = {40}, number = {20}, pages = {1823-1828}, pmid = {2218345}, issn = {0035-2640}, mesh = {Animals ; Asbestos/adverse effects ; Cell Transformation, Neoplastic/pathology ; Fibrosis/physiopathology ; Humans ; Mesothelioma/chemically induced/genetics/*physiopathology ; Pleura/*pathology/physiopathology ; Pleural Neoplasms/chemically induced/genetics/*physiopathology ; Rats ; }, abstract = {Mesothelial cells are described in situ at the surface of the pleura. Their functions are discussed, in relation with the inflammatory response to different agents (infectious agents, mineral fibres...) and with the carcinogenic transformation, particularly in relation to asbestos exposure. The mechanisms of fibrogenesis, either symphysis or pleural plaques, are not clearly understood. The numerous studies now in progress on the different steps and mechanisms of mesothelial transformation and mesothelioma genesis are summarized focusing on the most recent cytogenetic and molecular biology findings.}, } @article {pmid2284446, year = {1990}, author = {Briceño, CE and Bértoli, F and Echavarría, A}, title = {[Diffuse malignant mesothelioma. Presentation of 10 cases and review of the literature].}, journal = {Revista medica de Panama}, volume = {15}, number = {3}, pages = {168-175}, pmid = {2284446}, issn = {0379-1629}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Mesothelioma/*pathology ; Middle Aged ; Pleural Effusion, Malignant/*pathology ; }, abstract = {The authors study ten cases of malignant diffuse mesothelioma diagnosed histologically in the CH-Dr-AAM-CSS. Of the ten cases eight were men and two women, from 22 to 73 years of age. No evidence of exposure to asbestos was elicited by the nature of their occupation or their place of residence. The clinical findings in all cases is similar to those found in this type of disease. The radiologic findings were limited: pleural effusion, pulmonary fibrosis, and pulmonary mass. To make a definitive diagnosis it was necessary to use an invasive procedure. Examination of sputum, bronchial washings and endobronchial biopsies did not contribute to the diagnosis. The cytological examination of pleural and ascitic fluid resulted in a diagnosis of malignancy. In four cases the diagnosis was made by closed pleural biopsy; in five other cases it was necessary to obtain specimens by thoracotomy. In the last case the diagnosis was made at autopsy. The authors reviewed the original slides and additional slides from the paraffin blocks of the biopsies and of the autopsy. The diagnoses made by the pathologists were listed according to the classification of the AFIP (1).}, } @article {pmid2234739, year = {1990}, author = {Gee, JB and Mossman, BT}, title = {Asbestos warrants care, management but society must resist urge to panic.}, journal = {Occupational health & safety (Waco, Tex.)}, volume = {59}, number = {10}, pages = {25}, pmid = {2234739}, issn = {0362-4064}, mesh = {*Asbestos ; *Attitude to Health ; Child ; *Environmental Exposure ; Humans ; Lung Neoplasms/etiology/prevention & control ; Mesothelioma/etiology/prevention & control ; Public Opinion ; }, } @article {pmid2231193, year = {1990}, author = {Dazzi, H and Thatcher, N and Hasleton, PS and Chatterjee, AK and Lawson, RA}, title = {DNA analysis by flow cytometry in malignant pleural mesothelioma: relationship to histology and survival.}, journal = {The Journal of pathology}, volume = {162}, number = {1}, pages = {51-55}, doi = {10.1002/path.1711620110}, pmid = {2231193}, issn = {0022-3417}, mesh = {Aged ; Asbestos/adverse effects ; DNA, Neoplasm/*analysis ; Female ; Flow Cytometry ; Humans ; Male ; Mesothelioma/*genetics/mortality/pathology ; Middle Aged ; Pleural Neoplasms/*genetics/mortality/pathology ; *Ploidies ; Retrospective Studies ; }, abstract = {In a retrospective study of 70 patients with malignant pleural mesothelioma, 168 formalin-fixed, paraffin-embedded tumour specimens were examined for DNA content by flow cytometry. In 20 patients where two or more blocks of the same tumour were available, there was considerable agreement between ploidy status and S-phase percentage in the different specimens. There were no significant differences for survival for patients who had been exposed to asbestos and those in whom no exposure could be elicited, nor for aneuploid and diploid tumours. The S-phase content was examined for different areas of the same tumour and the percentages were largely in agreement. However, those patients who had tumours with an S-phase percentage greater than the median (6 per cent) had a significantly shorter survival than those with tumours of lower S-phase percentage. Differences in DNA content and other cell cycle parameters were not associated with the histological subtypes.}, } @article {pmid2218970, year = {1990}, author = {Gibbs, AR}, title = {Role of asbestos and other fibres in the development of diffuse malignant mesothelioma.}, journal = {Thorax}, volume = {45}, number = {9}, pages = {649-654}, pmid = {2218970}, issn = {0040-6376}, mesh = {Animals ; Asbestos/*adverse effects ; Disease Models, Animal ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; Rats ; }, } @article {pmid2207033, year = {1990}, author = {Gibbs, AR and Griffiths, DM and Pooley, FD and Jones, JS}, title = {Comparison of fibre types and size distributions in lung tissues of paraoccupational and occupational cases of malignant mesothelioma.}, journal = {British journal of industrial medicine}, volume = {47}, number = {9}, pages = {621-626}, pmid = {2207033}, issn = {0007-1072}, mesh = {Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Female ; Humans ; Lung/pathology ; Lung Neoplasms/*etiology/pathology ; Male ; Mesothelioma/*etiology/pathology ; Middle Aged ; Occupational Diseases/*etiology/pathology ; Respiratory Protective Devices ; }, abstract = {The results of analysis of mineral fibres in lung tissues from 10 paraoccupational cases of malignant mesothelioma were compared with analysis obtained from seven cases of malignant mesotheliomas that had developed in gas mask workers. Nine of the paraoccupational cases were considered to have developed their tumours because of exposure to asbestos on their husbands' working clothes and one cancer developed in the daughter of a man who had died of asbestosis. The gas mask workers had direct exposure to asbestos while working in a factory that produced military gas masks. The results of mineral fibre analysis in the paraoccupational cases were variable; six showed high crocidolite concentrations, seven raised amosite concentrations and two normal concentrations of all types of asbestos fibre measured. Chrysotile was raised in one case but crocidolite and amosite were also increased. The gas mask workers showed a consistent pattern with high crocidolite concentrations and normal or low concentrations of chrysotile and amosite. Fibre lengths for chrysotile were similar in both groups and predominantly less than 5 microns. Crocidolite fibres tended to be longer in the gas mask workers than in the paraoccupational group and longer than chrysotile in both groups. Amosite fibres tended to be more variable in width than those of chrysotile or crocidolite.}, } @article {pmid2207031, year = {1990}, author = {Albin, M and Jakobsson, K and Attewell, R and Johansson, L and Welinder, H}, title = {Mortality and cancer morbidity in cohorts of asbestos cement workers and referents.}, journal = {British journal of industrial medicine}, volume = {47}, number = {9}, pages = {602-610}, pmid = {2207031}, issn = {0007-1072}, mesh = {Asbestos/*adverse effects ; Cohort Studies ; Colorectal Neoplasms/etiology/mortality ; Humans ; Lung Diseases/etiology/*mortality ; Lung Neoplasms/etiology/mortality ; Male ; Mesothelioma/etiology/mortality ; Neoplasms/etiology/*mortality ; Occupational Diseases/etiology/*mortality ; Pleural Neoplasms/mortality ; Risk ; Sweden/epidemiology ; Time Factors ; }, abstract = {Total and cause specific mortality and cancer morbidity were studied among 1929 asbestos cement workers with an estimated median cumulative exposure of 2.3 fibre (f)-years/ml (median intensity 1.2 f/ml, predominantly chrysotile). A local reference cohort of 1233 industrial workers and non-case referents from the exposed cohort were used for comparisons. The risk for pleural mesothelioma was significantly increased (13 cases out of 592 deaths in workers with at least 20 years latency). No case of peritoneal mesothelioma was found. A significant dose response relation was found for cumulative exposure 40 years or more before the diagnosis, with a multiplicative relative risk (RR) of 1.9 for each f-year/ml. No relation was found with duration of exposure when latency was accounted for. There was a significant overrisk in non-malignant respiratory disease (RR = 2.6). The overall risks for respiratory cancer, excluding mesothelioma, and for gastrointestinal cancer were not significantly increased. Surprisingly, colorectal cancer displayed a clear relation with cumulative dose, with an estimated increase of 1.6% in the incidence density ratio for each f-year/ml (but not with duration of exposure).}, } @article {pmid2171325, year = {1990}, author = {Huncharek, M}, title = {Brake mechanics, asbestos, and disease risk.}, journal = {The American journal of forensic medicine and pathology}, volume = {11}, number = {3}, pages = {236-240}, doi = {10.1097/00000433-199009000-00012}, pmid = {2171325}, issn = {0195-7910}, mesh = {Asbestos/*adverse effects ; Asbestos, Serpentine ; Asbestosis/epidemiology/etiology ; *Automobiles ; Humans ; Lung Neoplasms/epidemiology/etiology ; Male ; Mesothelioma/epidemiology/etiology ; Occupational Diseases/epidemiology/*etiology ; *Occupational Exposure ; Risk Factors ; }, abstract = {Health risks posed by inhalable asbestos fibers are known to exist in a variety of industrial and nonindustrial settings. Although early studies described an increased risk of asbestosis, lung cancer, and mesothelioma in asbestos-industry workers, subsequent research revealed the existence of a potential asbestos-related health hazard in nonasbestos industries such as the textile and railroad industries. Brake mechanics and garage workers constitute a large work force with potential exposures to levels of asbestos capable of producing disease. Unfortunately, the health risk faced by these workers has received little attention. This article briefly discusses currently available information on the asbestos health risks of workers in this setting, and highlights the need for further investigations of this occupational group.}, } @article {pmid2169860, year = {1990}, author = {Neuberger, M and Kundi, M}, title = {Individual asbestos exposure: smoking and mortality--a cohort study in the asbestos cement industry.}, journal = {British journal of industrial medicine}, volume = {47}, number = {9}, pages = {615-620}, pmid = {2169860}, issn = {0007-1072}, mesh = {Asbestos/*adverse effects ; Asbestos, Crocidolite ; Asbestos, Serpentine ; Austria/epidemiology ; Cohort Studies ; Dust/adverse effects ; Humans ; Life Tables ; Lung Neoplasms/etiology/*mortality ; Male ; Mesothelioma/etiology/*mortality ; Occupational Diseases/etiology/*mortality ; Occupational Exposure ; Prospective Studies ; Risk ; *Smoking ; Time Factors ; }, abstract = {A historical prospective cohort study comprised all persons employed from 1950 to 1981 for at least three years in the oldest asbestos cement factory in the world. From 2816 persons eligible for the study, record based estimates and measurements of dust and fibres and histories of smoking based on interviews were used to calculate individual exposures over time. After observation of 51,218 person-years and registration of 540 deaths, underlying causes of death for this cohort were compared with those for the regional population on the basis of death certificates. Deaths from lung cancer in asbestos cement workers were higher (standard mortality ratio (SMR) 1.7), but after adjustment for age and sex specific smoking habits this was not significant (SMR 1.04). The study had a probability of greater than 92% of detecting a smoking adjusted SMR of 1.5 or more. Using the best available evidence (including necropsy records) 52 deaths were assigned to lung cancer and five to mesothelioma. Life table analyses confirmed the predominant influence of smoking on lung cancer. Mesothelioma was associated with the use of crocidolite in pipe production. From present working conditions with much lower concentrations of chrysotile and no crocidolite no more occupational cancers are expected in the asbestos cement industry.}, } @article {pmid2168090, year = {1990}, author = {McDonald, JC and McDonald, AD}, title = {Asbestos and carcinogenicity.}, journal = {Science (New York, N.Y.)}, volume = {249}, number = {4971}, pages = {844}, doi = {10.1126/science.2168090}, pmid = {2168090}, issn = {0036-8075}, mesh = {Asbestos/*adverse effects ; Asbestos, Serpentine ; Cohort Studies ; Humans ; Mesothelioma/*etiology ; Mining ; Occupational Diseases/*etiology ; }, } @article {pmid2272328, year = {1990}, author = {Lippmann, M}, title = {Effects of fiber characteristics on lung deposition, retention, and disease.}, journal = {Environmental health perspectives}, volume = {88}, number = {}, pages = {311-317}, pmid = {2272328}, issn = {0091-6765}, support = {CA 13343/CA/NCI NIH HHS/United States ; ES-00260/ES/NIEHS NIH HHS/United States ; ES-00881/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Asbestos/adverse effects ; Asbestosis/etiology ; Humans ; Lung Diseases/*etiology ; Minerals/*adverse effects/chemistry/metabolism ; Particle Size ; Respiratory System/metabolism ; }, abstract = {There is abundant epidemiologic evidence that asbestos fibers can cause lung fibrosis (asbestosis), bronchial cancer, and mesothelioma in humans, as well as limited evidence for such effects in workers exposed to slag and rockwool fibers. Epidemiological evidence for human disease from inhalation exposures to conventional fibrous glass is negative. While health concerns based on the morphological and toxicological similarities between man-made fibers and asbestos are warranted, it is important to note that most of the toxicological evidence for glass fiber toxicity in laboratory animals is based on nonphysiological exposures such as intratracheal instillation or intraperitoneal injection of fiber suspensions. Man-made fibers have produced lung fibrosis and mesotheliomas in such tests, albeit at much lower yields than asbestos. For all durable mineral fibers, critical length limits must be exceeded to warrant concern about chronic toxicity; i.e., 2 microns for asbestosis, 5 microns for mesothelioma, and 10 microns for lung cancer. Fiber width must be less than 0.1 microns for mesothelioma, and larger than this limit for asbestosis and lung cancer. The human health risks for most fibrous glass products are either low or negligible for a variety of reasons. First, most commercial fibrous glass products have mean fiber diameters of approximately 7.5 microns, which results in mean aero-dynamic diameters approximately 22 microns. Thus, most glass fibers, even if dispersed into the air, do not penetrate into the lung to any great extent. Second, the small fraction of smaller diameter fibers that do penetrate into the lungs are not persistent within the lungs for most fibrous glass products due to mechanical breakage into shorter lengths and overall dissolution.(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid2272326, year = {1990}, author = {Roggli, VL}, title = {Human disease consequences of fiber exposures: a review of human lung pathology and fiber burden data.}, journal = {Environmental health perspectives}, volume = {88}, number = {}, pages = {295-303}, pmid = {2272326}, issn = {0091-6765}, mesh = {Asbestos/adverse effects ; Asbestosis/etiology/pathology ; Humans ; Lung Diseases/*etiology/pathology ; Lung Neoplasms/etiology/pathology ; Mesothelioma/etiology/pathology ; Minerals/*adverse effects ; Pleural Diseases/etiology/pathology ; }, abstract = {Inhalation of asbestos fibers results in a variety of neoplastic and nonneoplastic diseases of the respiratory tract. Some of these diseases, such as asbestosis, generally occur after prolonged and intensive exposure to asbestos, whereas others, such as pleural mesothelioma, may occur following brief exposures. Inhalation of nonasbestiform mineral fibers can occur as well, and these fibers can be recovered from human lung tissue. Thus, there has been considerable interest in the relationship between mineral fiber content of the lung and various pathologic changes. Techniques for fiber analysis of human tissues have not been standardized, and consequently results may differ appreciably from one laboratory to another. In all reported series, extremely high fiber burdens are found in the lungs of individuals with asbestosis. Although there is a correlation between the tissue concentration of asbestos fibers and the severity of pulmonary fibrosis, further studies of the mineralogic correlates of fiber-induced pulmonary fibrosis are needed. Mesothelioma may occur with fiber burdens considerably less than those necessary to produce asbestosis. More information is needed regarding the migration of fibers to the pleura and the numbers, types, and dimensions of fibers that accumulate at that site. Patients with asbestosis have a markedly increased risk for lung cancer, but the risk of lung cancer attributable to asbestos in exposed workers without asbestosis who also smoke is controversial. Combined epidemiologic-mineralogic studies of a well-defined cohort are needed to resolve this issue. In addition, more information is needed regarding the potential role of nonasbestos mineral fibers in the pathogenesis of lung cancer.}, } @article {pmid2272325, year = {1990}, author = {Merchant, JA}, title = {Human epidemiology: a review of fiber type and characteristics in the development of malignant and nonmalignant disease.}, journal = {Environmental health perspectives}, volume = {88}, number = {}, pages = {287-293}, pmid = {2272325}, issn = {0091-6765}, mesh = {Asbestos/*adverse effects ; Asbestosis/epidemiology/etiology ; Humans ; Lung Neoplasms/epidemiology/etiology ; Mesothelioma/epidemiology/etiology ; Minerals/*adverse effects ; Neoplasms/epidemiology/*etiology ; Pleural Diseases/epidemiology/etiology ; Respiratory Tract Diseases/epidemiology/*etiology ; Silicon/adverse effects ; }, abstract = {Consideration of the human epidemiology of diseases arising from exposure to naturally occurring and man-made mineral fibers encompasses the several forms of asbestos (chrysotile, crocidolite, amosite, anthophyllite, tremolite-actinolite), other naturally occurring silicates (talc, sepiolite, erionite, attapulgite, vermiculite, and wollastonite), and man-made mineral fibers (glass continuous filament, glass/rock/slag insulation wools, ceramic and other refractory fibers, and glass microfibers). The diseases arising from exposures to some of these fibers include pleural thickening (plaques, diffuse pleural thickening, and calcification), pulmonary fibrosis, lung cancers, mesothelioma of the pleura and peritoneum, and other cancers). Risk factors important in assessing these diseases include assessment of latency, duration of exposure, cumulative exposure, fiber origin and characteristics (length and diameter), other possible confounding occupational or environmental exposures, and smoking. Methodological issues commonly presenting problems in evaluation of these data include assessment of the adequacy of environmental exposures, particularly in regard to fiber identification, distribution, and concentration over the duration of exposure, and the adequacy of study design to detect health effects (disease frequency, latency, and cohort size). Research priorities include further assessment and standardization of pleural thickening relative to fiber exposure, uniform mesothelioma surveillance, further epidemiological assessment of certain silicate and man-made mineral fiber cohorts with emphasis given to assessment of tremolite and small diameter glass and ceramic fibers. Further assessment of possible health risks of the general public should await improved definition of relevant fiber exposure in ambient air.}, } @article {pmid2243458, year = {1990}, author = {Kishimoto, T}, title = {[Respiratory malignancies induced by asbestos exposure and evaluation of cases with typical pleural malignant mesothelioma and lung cancer with asbestosis].}, journal = {Nihon Kyobu Shikkan Gakkai zasshi}, volume = {28}, number = {8}, pages = {1078-1084}, pmid = {2243458}, issn = {0301-1542}, mesh = {Aged ; Asbestosis/*complications/pathology ; Humans ; Lung/*pathology ; Lung Neoplasms/*etiology/pathology ; Male ; Mesothelioma/*etiology/pathology ; Middle Aged ; }, abstract = {Asbestos exposure induces lung fibrosis, i.e. asbestosis, and furthermore, pathological changes of pleura, i.e. asbestos pleurisy of pleural plaque. Generally, asbestosis is induced by massive exposure to asbestos and pleural changes are induced by low dose exposure to asbestos. The most important diseases which are induced by asbestos exposure are malignancies, especially malignant mesothelioma and lung cancer. Two cases, one malignant mesothelioma, the other lung cancer with asbestosis induced by asbestos exposure received almost the same dose of asbestos, as estimated from the period of asbestos exposure and occupational history and the same kind of asbestos (crocidolite) and had a smoking history. We do not know which elements may induce malignancies under asbestos exposure. Recently, some reports described that asbestos mediated the transformation of genes and this action induced malignancies. We should extend our study to the gene problem in cases of malignant mesothelioma and lung cancer induced by asbestos exposure.}, } @article {pmid2168201, year = {1990}, author = {Reger, R and Morgan, WK}, title = {On talc, tremolite, and tergiversation.}, journal = {British journal of industrial medicine}, volume = {47}, number = {8}, pages = {505-507}, pmid = {2168201}, issn = {0007-1072}, mesh = {Aged ; Asbestos/adverse effects ; *Asbestos, Amphibole ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/etiology ; Middle Aged ; Occupational Diseases/*etiology ; Silicic Acid/*adverse effects ; Silicon Dioxide/*adverse effects ; Talc/*adverse effects ; }, } @article {pmid2090351, year = {1990}, author = {}, title = {[An analysis of 310 cases of pleural mesothelioma].}, journal = {Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases}, volume = {13}, number = {4}, pages = {216-20, 254-5}, pmid = {2090351}, issn = {1001-0939}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Female ; Humans ; Male ; *Mesothelioma/diagnosis/etiology/therapy ; Middle Aged ; *Pleural Neoplasms/diagnosis/etiology/therapy ; }, abstract = {The analysis of 310 cases of pleural mesothelioma collected from 53 hospitals in 22 provinces in China is presented. There were 200 male and 110 female patients, and the median of their age was 44.2 years (5-83), with a mean 45.2 years. Only 9 cases (2.9%) with definite history of asbestos exposure. The most common symptoms at onset of disease were chest pain, short of breath and cough, but it was fever at clinical presentation in 10.2%, and arthralgia in 3.2% of patients. Pleural effusion was seen in 60.3% of patients, while 3/4 were bloody. The most common roentgenological findings were solitary or multiple pleural nodular lesions. There were 86 cases (27.7%) diagnosed as solitary type, and the others diffuse type. Histologically, there were 32.5% as epithelial type and 53.4% as fibrotic type, and 14.1% as mixed type, two cellular components could be seen simultaneously or sequentially during the course of disease. Follow-up of 154 cases received surgery, chemotherapy and irradiation, revealed that 37(24%) survived more than 3 years, the longest being 22 years after treatment. The possible relationship between asbestos exposure and pleural mesothelioma in China, clinical features, criteria of diagnosis and treatment are discussed.}, } @article {pmid2399229, year = {1990}, author = {Konetzke, GW and Beck, B and Mehnert, WH}, title = {[Occupational and non-occupational effects of asbestos].}, journal = {Pneumologie (Stuttgart, Germany)}, volume = {44}, number = {7}, pages = {858-861}, pmid = {2399229}, issn = {0934-8387}, mesh = {Air Pollutants, Occupational/*adverse effects ; Asbestos/*adverse effects ; Asbestosis/*epidemiology ; Cross-Sectional Studies ; Dust/*adverse effects ; Female ; Germany, East/epidemiology ; Humans ; Incidence ; Male ; Mesothelioma/*epidemiology ; Peritoneal Neoplasms/*epidemiology ; Pleural Neoplasms/*epidemiology ; Risk Factors ; }, abstract = {Forty-eight cases of mesothelioma from the National Cancer Register, and 19 cases of pleural plaques were investigated for non-occupational exposure to asbestos, and compared with results obtained in earlier studies on occupational asbestos-induced lesions. The results of the investigation confirmed reports in the literature indicating that even in the non-occupational area, asbestos represents a non-negligible risk, in particular for diseases of the lungs. Individual causes proved to be the cleaning by members of the family of working clothes contaminated with asbestos in 46% of the cases, followed by the use of asbestos-containing materials in the household (20.9%) or in connection with leisure activities (14.9%). In addition, exposure to asbestos fibre emissions of people living close to an asbestos-processing plant were observed. Recognition of the condition as an occupation-related disease is not possible. The consequence to be drawn from these data is that, in accordance with present regulations, the use of asbestos-free materials in the home and in the area of leisure activities must be promoted. In this way, such lesions can be avoided in the future.}, } @article {pmid2373539, year = {1990}, author = {Desai, DC and Swaroop, VS and Mohandas, KM and Dhir, V and Nagral, A and Krishnamurthy, S}, title = {Primary peritoneal mesothelioma.}, journal = {Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology}, volume = {9}, number = {3}, pages = {241}, pmid = {2373539}, issn = {0254-8860}, mesh = {Asbestos/*adverse effects ; Humans ; Male ; Mesothelioma/*etiology ; Middle Aged ; Occupational Diseases/*etiology ; Peritoneal Neoplasms/*etiology ; Time Factors ; }, abstract = {A patient with primary peritoneal mesothelioma who had occupational exposure to asbestos 30 years ago is reported. The disease was progressive and the patient died 12 months after the diagnosis.}, } @article {pmid2357680, year = {1990}, author = {Hagemeijer, A and Versnel, MA and Van Drunen, E and Moret, M and Bouts, MJ and van der Kwast, TH and Hoogsteden, HC}, title = {Cytogenetic analysis of malignant mesothelioma.}, journal = {Cancer genetics and cytogenetics}, volume = {47}, number = {1}, pages = {1-28}, doi = {10.1016/0165-4608(90)90258-c}, pmid = {2357680}, issn = {0165-4608}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; *Chromosome Aberrations ; Chromosome Banding ; Female ; Genetic Markers ; Humans ; Karyotyping ; Male ; Mesothelioma/etiology/*genetics/mortality/pathology ; Middle Aged ; Pleural Neoplasms/etiology/*genetics/mortality/pathology ; Ploidies ; }, abstract = {Cytogenetic analyses of 40 confirmed malignant mesotheliomas (MMs) are reported. Pleural effusion cells were studied in 90% of the cases by direct method or after culture or both. Biopsy and ascites fluid were also analyzed in some patients. A normal karyotype was found in nine cases, and complex karyotypic abnormalities were observed in 30 cases. In one case, analyzable metaphases were not obtained. The chromosomal changes were all complex and heterogeneous; no consistent presumably specific abnormality was detected. Nevertheless, two main patterns of nonrandom abnormalities were observed: 1) loss of chromosomes 4 and 22, 9p, and 3p in the most of the abnormal cases and corresponding to a hypodiploid and/or hypotetraploid modal chromosome number; and 2) gain of chromosomes 7, 5, and 20 with deletion or rearrangement of 3p as well in the hyperdiploid cases, which were a minority in our series. These findings are discussed in view of other reported cytogenetic studies of MM, asbestos exposure, and possible mechanisms of malignant transformation.}, } @article {pmid2232322, year = {1990}, author = {Morinaga, K and Hara, I and Yasui, I and Yokoyama, K and Sera, Y}, title = {[Twenty years' follow-up study of asbestos workers].}, journal = {Sangyo igaku. Japanese journal of industrial health}, volume = {32}, number = {4}, pages = {265-268}, doi = {10.1539/joh1959.32.265}, pmid = {2232322}, issn = {0047-1879}, mesh = {Adult ; Age Factors ; Asbestosis/*epidemiology/mortality ; Cohort Studies ; Female ; Humans ; Japan/epidemiology ; Lung Neoplasms/*epidemiology/mortality ; Male ; Middle Aged ; Occupational Diseases/*epidemiology/mortality ; *Occupational Exposure ; Risk ; Sex Factors ; Survival Rate ; Time Factors ; }, abstract = {This report describes a cohort study conducted on workers who were employed in a factory mainly manufacturing asbestos yarn and cloth and were followed from 1964 to 1981. A total of 208 workers (73 males and 135 females) could be traced and 15 deaths were observed by the end of 1983. Among them, three had lung cancer and its relative risk was 6.8 (p less than 0.05) computed based on the age, sex and year specific death rates of Osaka Prefecture. One case of peritoneal mesothelioma was also found. The period from first asbestos exposure to death of these four cases of asbestos-related malignancies was more than 25 yr. In the analysis of the employees who had more than 1 yr of exposure to asbestos and those who had already been engaged in this factory at the beginning of the observation, the relative risk of lung cancer was 8.1 and 13.6, respectively.}, } @article {pmid2217155, year = {1990}, author = {Roggli, VL and Benning, TL}, title = {Asbestos bodies in pulmonary hilar lymph nodes.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {3}, number = {4}, pages = {513-517}, pmid = {2217155}, issn = {0893-3952}, mesh = {Aged ; Asbestos/*adverse effects ; Asbestosis/etiology/pathology ; Female ; Humans ; Lung Neoplasms/etiology/pathology ; Lymph Nodes/*pathology ; Male ; Mesothelioma/etiology/pathology ; Microscopy, Electron, Scanning ; Middle Aged ; Pleural Neoplasms/etiology/pathology ; }, abstract = {Asbestos bodies (AB) have long been recognized in light microscopic (LM) sections of pulmonary hilar lymph nodes (LN) from patients with asbestos-related diseases, but the presence of AB on LM has not been correlated with the lung AB burden. The purpose of the present study was to determine whether AB in histologic sections of LN are indicative of heavy lung asbestos burdens. Twenty cases (17 with asbestosis, 15 with carcinoma of the lung, and two with malignant pleural mesothelioma) with at least one AB on a hilar LN section were identified. Bleach digestion of lung tissue in 15 cases demonstrated a median of 24,000 AB/g by LM and 44,000 AB/g by scanning electron microscopy. Digestion of hilar nodes demonstrated 21,800, 15,500, and 3,200 AB/g by LM in three cases which had lung burdens of 22,000, 481,000, and 5470 AB/g, respectively. A fourth LN specimen contained 322,000 AB/g in a case with no lung available to digest. Mean AB lengths in the LN in three cases were 48, 45, and 27 microns. Fourteen control cases of men over 50 without known asbestos exposure or asbestos-related disease had no AB in LN sections even after staining for iron. Among fourteen patients with parietal pleural plaques and an elevated lung asbestos body content, AB were observed in iron-stained LN sections in only two cases. These two patients had 3240 and 610 AB/g lung tissue, respectively (normal range 0 to 20 AB/g). We conclude that the finding of AB on a histologic section of hilar LN is generally indicative of a heavy lung AB burden.(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid2377094, year = {1990}, author = {Ferguson, D}, title = {Low-level asbestos--the priorities are wrong.}, journal = {The Medical journal of Australia}, volume = {152}, number = {12}, pages = {617-618}, doi = {10.5694/j.1326-5377.1990.tb125412.x}, pmid = {2377094}, issn = {0025-729X}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Australia ; Female ; Humans ; Lung Neoplasms/*chemically induced/epidemiology ; Male ; Mesothelioma/*chemically induced/epidemiology ; Middle Aged ; Occupational Diseases/*chemically induced/epidemiology ; }, } @article {pmid2143221, year = {1990}, author = {Smith, AH and Handley, MA and Wood, R}, title = {Epidemiological evidence indicates asbestos causes laryngeal cancer.}, journal = {Journal of occupational medicine. : official publication of the Industrial Medical Association}, volume = {32}, number = {6}, pages = {499-507}, doi = {10.1097/00043764-199006000-00005}, pmid = {2143221}, issn = {0096-1736}, mesh = {Alcoholic Beverages/*adverse effects ; Asbestos/*adverse effects ; Environmental Exposure ; Epidemiologic Factors ; Humans ; Laryngeal Neoplasms/epidemiology/*etiology ; Mesothelioma/epidemiology/*etiology ; Meta-Analysis as Topic ; Research Design/standards ; Smoking/*adverse effects ; }, abstract = {A variety of opinions have been expressed in the literature concerning asbestos and laryngeal cancer. This paper presents an analysis of epidemiological studies based on criteria that prioritized the most heavily exposed cohorts. Emphasis was given to the six cohorts or subcohorts with lung cancer relative risk estimates of 2 or more. The two groups of workers with the highest lung cancer relative risk estimates (4.06 and 3.28) both gave strong support for a causal association of asbestos and laryngeal cancer, with relative risk estimates of 1.91 (90% confidence limits 1.00 to 3.34) and 3.75 (90% confidence limits 1.01 to 9.68), respectively. Confounding with cigarette smoking or alcohol consumption does not explain the findings. Case-control studies gave mixed results, but generally supported the hypothesis. It was concluded that asbestos is a probable cause of laryngeal cancer in view of the reasonable consistency of the studies, the strength of the association in key studies, the evidence for dose-response relationships, and the biological plausibility for asbestos being a cause of laryngeal cancer.}, } @article {pmid2393241, year = {1990}, author = {Chia, SE and Lee, HS}, title = {Malignant mesothelioma in a clerk working in an asbestos factory.}, journal = {Annals of the Academy of Medicine, Singapore}, volume = {19}, number = {3}, pages = {380-381}, pmid = {2393241}, issn = {0304-4602}, mesh = {Air Pollutants, Occupational/analysis ; Asbestos/*adverse effects ; Humans ; Lung Neoplasms/diagnosis/*etiology ; Male ; Mesothelioma/*etiology ; Middle Aged ; Occupational Diseases/*etiology ; Singapore ; }, abstract = {Mesothelioma is a rare cancer which is associated with asbestos exposure. Generally most medical professionals are aware of this. However, not many of them may realise that individuals could develop asbestos related mesothelioma as a result of 'bystander' exposure. We report here a case of asbestos related pleural mesothelioma in a clerk who was not directly exposed to asbestos. The patient presented with signs and symptoms of a massive right pleural effusion. The diagnosis of a malignant diffuse pleural mesothelioma was made only after the pleural tissue (obtained during the thoracotomy) was sent for histology. Patient was started on chemotherapy but he succumbed to the disease and died ten months after the onset of the first symptoms. The risk of developing mesothelioma among individuals who are not directly working with asbestos is discussed in this report.}, } @article {pmid2102724, year = {1990}, author = {Gutiérrez-Rave Pecero, VM and Luque Márquez, R and Andrada Becerra, E and Creagh Cerquera, R and Suárez García, E and Pujol de la Llave, E}, title = {[Peritoneal mesothelioma: the importance of ultrastructural study. A report of 2 cases and a review of the Spanish literature].}, journal = {Anales de medicina interna (Madrid, Spain : 1984)}, volume = {7}, number = {5}, pages = {261-264}, pmid = {2102724}, issn = {0212-7199}, mesh = {Aged ; Anemia, Hemolytic, Autoimmune/diagnosis/etiology/pathology ; Biopsy ; Female ; Humans ; Mesothelioma/complications/diagnosis/*ultrastructure ; Middle Aged ; Peritoneal Neoplasms/complications/diagnosis/*ultrastructure ; Peritoneum/pathology ; }, abstract = {Two cases of peritoneal mesothelioma (PM), with ultrastructural study, of females who lived in a rural area without asbestos exposition history are described and the Spanish literature reviewed. We highlight the association with severe autoimmune hemolytic anemia, due to the presence of cold agglutinins, in one patient without relationship to drugs or concomitant diseases. We focus on the need for thorough and multiple biopsies through laparoscopy to avoid false negative. We believe that there are no totally specific morphological data on mesothelioma, which means that the initial study is based on optical microscopy performed with hematoxylin-eosin and PAS-diastase stain using the electronic microscopy to confirm the diagnosis.}, } @article {pmid2235715, year = {1990}, author = {Szeszenia-Dabrowska, N}, title = {[Health hazards of occupational exposure to asbestos dust].}, journal = {Polski tygodnik lekarski (Warsaw, Poland : 1960)}, volume = {45}, number = {14-15}, pages = {309-312}, pmid = {2235715}, issn = {0032-3756}, mesh = {Air Pollutants, Occupational/*adverse effects ; Asbestos/*adverse effects ; Asbestosis/*etiology ; Dust/adverse effects ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Peritoneal Neoplasms/*etiology ; Pleural Neoplasms/*etiology ; }, } @article {pmid2337536, year = {1990}, author = {Lerman, Y and Finkelstein, A and Levo, Y and Tupilsky, M and Baratz, M and Solomon, A and Sackstein, G}, title = {Asbestos related health hazards among power plant workers.}, journal = {British journal of industrial medicine}, volume = {47}, number = {4}, pages = {281-282}, pmid = {2337536}, issn = {0007-1072}, mesh = {Aged ; Asbestos/*adverse effects ; Humans ; Male ; Mesothelioma/*etiology/pathology ; Middle Aged ; Occupational Diseases/*etiology/pathology ; Pleural Effusion/etiology ; Pleural Neoplasms/*etiology/pathology ; *Power Plants ; }, } @article {pmid2323006, year = {1990}, author = {Pelin-Enlund, K and Husgafvel-Pursiainen, K and Tammilehto, L and Klockars, M and Jantunen, K and Gerwin, BI and Harris, CC and Tuomi, T and Vanhala, E and Mattson, K}, title = {Asbestos-related malignant mesothelioma: growth, cytology, tumorigenicity and consistent chromosome findings in cell lines from five patients.}, journal = {Carcinogenesis}, volume = {11}, number = {4}, pages = {673-681}, doi = {10.1093/carcin/11.4.673}, pmid = {2323006}, issn = {0143-3334}, mesh = {Adult ; Animals ; Asbestos/*adverse effects ; Carcinogenicity Tests ; Cell Division ; Histocytochemistry ; Humans ; Karyotyping ; Male ; Mesothelioma/etiology/genetics/metabolism/*pathology ; Mice ; Mice, Nude ; Microscopy, Electron, Scanning ; Middle Aged ; Pleural Neoplasms/etiology/genetics/metabolism/*pathology ; Tumor Cells, Cultured ; }, abstract = {Seven mesothelioma cell lines were established from clinical specimens from five patients with asbestos-related malignant pleural mesothelioma. The cells in culture show either epithelial or mixed epithelial/fibrosarcomatous growth with an average doubling time of 30 h. Giant multinucleated cells are common in all the cell lines, as well as long thin microvilli on the cell surfaces. All cell lines were cytokeratin positive and they stained negatively for monocyte-macrophage markers. All seven cell lines and one long-term tissue culture from a sixth mesothelioma patient were characterized cytogenetically. Karyotype analyses revealed complex structural and numerical abnormalities, primarily involving chromosome 1, 4, 5, 6, 7, 8, 9, 11, 12, 13 and 22. An excess of chromosome material of the short arm of chromosome 5 was seen consistently in six cell lines and in the long-term culture. In cell lines from four patients, changes in chromosome 13, mainly monosomy 13, were observed. The marker chromosomes observed in the early passages were conserved and few additional changes appeared in later passages. Six of the cell lines tested for tumorigenicity in athymic nude mice were weakly positive.}, } @article {pmid2139990, year = {1990}, author = {Hartmann, W}, title = {[Expert assessment of asbestos-induced lung damage].}, journal = {Versicherungsmedizin}, volume = {42}, number = {2}, pages = {49-52}, pmid = {2139990}, issn = {0933-4548}, mesh = {Asbestosis/*diagnosis ; Disability Evaluation ; Expert Testimony/*legislation & jurisprudence ; Humans ; Lung Neoplasms/*diagnosis ; Occupational Diseases/*diagnosis ; Workers' Compensation/*legislation & jurisprudence ; }, abstract = {Asbestos is a mineral of special technical properties and therefore used in many products all over the world. The inhalation of asbestos causes chronic inflammation of lung--the asbestosis--and pleura--pleuraplaques and pleuritis--and is responsible for mesothelioma and lung cancer. Under normal conditions the diagnosis asbestosis is easy because of the typical x-ray findings and the history of intensive exposure of asbestos. In rare conditions the history of exposure is uncertain and the diagnosis might be difficult. The expected anuity depends on the loss of lung-function. First we find a restrictive ventilatory disorder i.e. a reduction in VC and compliance. Later after progress of the disease the gasexchange is impaired. In case of mesothelioma or lungcancer the person is generally expected to be unable to work.}, } @article {pmid2156140, year = {1990}, author = {Berry, G and de Klerk, NH}, title = {Crocidolite and mesothelioma.}, journal = {The Medical journal of Australia}, volume = {152}, number = {6}, pages = {330-331}, pmid = {2156140}, issn = {0025-729X}, mesh = {Asbestos/*adverse effects ; Asbestos, Crocidolite ; Asbestosis/complications/epidemiology ; Australia/epidemiology ; Humans ; Incidence ; Lung Neoplasms/*epidemiology ; Mesothelioma/*epidemiology/mortality ; *Models, Statistical ; Risk ; Survival Rate ; }, } @article {pmid2306689, year = {1990}, author = {Kane, MJ and Chahinian, AP and Holland, JF}, title = {Malignant mesothelioma in young adults.}, journal = {Cancer}, volume = {65}, number = {6}, pages = {1449-1455}, doi = {10.1002/1097-0142(19900315)65:6<1449::aid-cncr2820650633>3.0.co;2-0}, pmid = {2306689}, issn = {0008-543X}, mesh = {Adult ; Female ; Humans ; Lung Neoplasms/diagnosis/*epidemiology/etiology ; Male ; Mesothelioma/diagnosis/*epidemiology/etiology ; }, abstract = {Ten cases of malignant mesothelioma presenting in patients 40 years old or younger at diagnosis were reviewed. Seven cases had a documented history of asbestos exposure of which five were household exposures. The median age at first exposure to asbestos was 10 years and the median duration of exposure was 120 months. The median latency period (time between initial asbestos exposure and diagnosis of malignant mesothelioma) was 19 years. The median interval from initial symptoms to definitive diagnosis was 5.5 months. The case history of each patient is presented. A significant delay in diagnosis in this age group compared with an age-unrestricted series is noted. The significance of nonoccupational exposure to asbestos is emphasized as a probable causative factor in the development of malignant mesothelioma. In addition, a possible genetic predisposition is briefly discussed.}, } @article {pmid2201808, year = {1990}, author = {Nagata, K and Sawai, S and Kishida, K and Watanabe, Y and Suehiro, I}, title = {[A case of malignant peritoneal mesothelioma diagnosed by ascitic fluid aspiration with a 28-year history of asbestos exposure].}, journal = {Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology}, volume = {87}, number = {3}, pages = {884-889}, pmid = {2201808}, issn = {0446-6586}, mesh = {Asbestos/*adverse effects ; Ascitic Fluid/*pathology ; Biopsy, Needle ; Environmental Exposure ; Humans ; Male ; Mesothelioma/diagnosis/*etiology/pathology ; Middle Aged ; Peritoneal Neoplasms/diagnosis/*etiology/pathology ; }, } @article {pmid2192481, year = {1990}, author = {Wheeler, CS}, title = {Exposure to man-made mineral fibers: a summary of current animal data.}, journal = {Toxicology and industrial health}, volume = {6}, number = {2}, pages = {293-307}, pmid = {2192481}, issn = {0748-2337}, mesh = {Air Pollutants/toxicity ; Animals ; Carcinogens ; Lung/metabolism ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Minerals/pharmacokinetics/*toxicity ; Particle Size ; }, abstract = {The inhalation of asbestos fibers (crocidolite, chrysotile and amosite) has been implicated in the development of a number of lung disorders including lung cancer, asbestosis, and mesothelioma. The mechanism responsible for these effects is not well characterized but is generally thought to be related to the fibrous nature of these materials. Therefore, concerns have also been raised as to the potential health impact of other fibrous materials including man-made mineral fibers. Man-made mineral fibers are being used as substitutes for asbestos in a wide range of products. However, relatively little data are available on the potential health impact of these fibrous materials. Epidemiology and clinical studies have served as an important source of information on the effect of various environmental pollutants, but have not been sufficient to date to fully address the potential health impact of man-made mineral fibers. This is due in part to the relatively recent introduction of a number of these materials, the long latency period before the onset of clinical symptoms, and in general, the lower exposure levels associated with these materials. Therefore, a number of animal studies have been performed to predict or confirm the toxicity of various man-made mineral fibers in humans. Both fibrosis and mesothelioma have been induced in experimental animals exposed to man-made mineral fibers although no disease has been consistently observed in occupationally exposed workers.2+ While little is known about the mechanism of this response, information from animal and cell culture experiments indicate that dose, fiber dimension, and fiber durability are the most important factors in determining the biological activity of these materials.(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid2192478, year = {1990}, author = {Lippmann, M}, title = {Man-made mineral fibers (MMMF): human exposures and health risk assessment.}, journal = {Toxicology and industrial health}, volume = {6}, number = {2}, pages = {225-246}, pmid = {2192478}, issn = {0748-2337}, support = {CA 13343/CA/NCI NIH HHS/United States ; ES-00260/ES/NIEHS NIH HHS/United States ; ES-00881/ES/NIEHS NIH HHS/United States ; }, mesh = {Air Pollutants, Occupational/analysis/toxicity ; Animals ; Environmental Exposure ; Glass ; Humans ; Lung/drug effects/metabolism ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Minerals/metabolism/*toxicity ; Particle Size ; Pulmonary Fibrosis/etiology ; Risk Factors ; }, abstract = {MMMF are made by spraying or extruding molten glass, furnace slag, or mineral rock. Health concerns are based on the morphological and toxicological similarities between MMMF and asbestos, and the well-documented evidence that asbestos fibers can cause lung fibrosis (asbestosis), bronchial cancer, and mesothelioma in humans. Epidemiological evidence for human disease from inhalation exposures to fibrous glass is largely negative. Some positive associations have been reported for slag and rockwools. Most of the toxicological evidence for MMMF toxicity in laboratory animals is based on non-physiological exposures such as intratracheal instillation or intraperitoneal injection of fiber suspensions. The risks for lung fibrosis, lung cancer, and mesothelioma for industrial exposures to most fibrous glass products are either low or negligible for a variety of reasons. First, most commercial fibrous glass products have mean fiber diameters of approximately 7.5 microns, which results in mean aerodynamic diameters greater than 22 microns. Thus, most glass fibers, even if dispersed into the air, do not penetrate into the lung to any great extent. Second, the small fraction of smaller diameter fibers which do penetrate into the lungs are not persistent within the lungs for most fibrous glass products, due to mechanical breakage into shorter lengths and dissolution. Dissolution is most rapid for the smaller diameters (less than 0.1 micron) capable of producing mesothelioma. The greater hazards for slag and rockwools, in comparison to conventional fibrous glass, appear to be related to their smaller diameters and greater durability within the lungs.}, } @article {pmid2164196, year = {1990}, author = {Ozesmi, M and Hillerdal, G and Krause, F}, title = {[Knowledge of carcinogenic and immunologic findings caused by the zeolite fiber erionite].}, journal = {Pneumologie (Stuttgart, Germany)}, volume = {44 Suppl 1}, number = {}, pages = {335-336}, pmid = {2164196}, issn = {0934-8387}, mesh = {Aluminum Silicates/*adverse effects ; Animals ; Cell Transformation, Neoplastic/pathology ; Dust/*adverse effects ; Female ; Humans ; Immunologic Deficiency Syndromes/*pathology ; Lung/pathology ; Lung Neoplasms/*pathology ; Male ; Mesothelioma/*pathology ; Pleura/pathology ; Pleural Neoplasms/*pathology ; Rats ; Rats, Inbred Strains ; Zeolites ; }, abstract = {Prompted by the unusually high death rate from cancer of the lungs, in 1975 in the Middle-Anatolian village of Karain, later in two other villages, X-ray screening investigations were carried out. These revealed pleural mesotheliomas similar to those seen following exposure to asbestos, although no asbestos was found neither in the village itself or in its immediate surroundings. Minerological tests and examinations of the lungs of the deceased, together with animal experiments involving dust obtained from the village itself, performed in 1980, demonstrated that erionite, a fibrous zeolite is responsible for tumour lesions in the lungs and pleura. Early stages of this tumour located in the pleura were also found in a group of Karain inhabitants working in Sweden. On the basis of the examination results, an immune deficiency that did not correlate with age, sex or duration of exposure was found, and thus cannot readily be classified as an epiphenomenon. Since fibrous zeolites are frequently employed in industry, industrial hygiene and occupational medical consequences need to be drawn.}, } @article {pmid2161274, year = {1990}, author = {Fang, D}, title = {[A study on the tumorigenic process of mesothelioma induced by intrapleural injection of crocidolite in rats].}, journal = {Zhonghua yi xue za zhi}, volume = {70}, number = {2}, pages = {88-90, 8}, pmid = {2161274}, issn = {0376-2491}, mesh = {Animals ; Asbestos/adverse effects ; Asbestos, Crocidolite ; Female ; Injections ; Male ; Mesothelioma/etiology/*pathology ; Pleura/pathology ; Pleural Neoplasms/etiology/*pathology ; Precancerous Conditions/etiology/*pathology ; Rats ; Rats, Inbred Strains ; }, abstract = {90 Wistar strain rats were used in this experiment, 56 rats (Group A) were injected intrapleurally with crocidolite fibers suspended in physiological (NaCl) solution. Another 34 rats (Group B), serving as controls, were injected with the same volume of mere NaCl solution. The rats were killed 1, 3, 6, 9, 12, 14 and 16 months respectively after injection. The results showed that the rats of Group B only exhibited reactive proliferation of mesothelial cells caused by inflammation. In Group A, there appeared 9 cases of mesothelioma. The tumorigenic stages of mesothelioma include three processes: (1). reactive proliferation: the mesothelial cells became cuboid. (2). precancerous changes: the atypical proliferation of stratified, nodular or papillary mesothelial cells and of the cell elements around asbestos granulomas. (3). the occurrence of mesothelioma. Ultrastructural observation revealed that in mesothelioma tissue mesenchymal cells directly or indirectly (via transitional cells) differentiated cinto epithelioid cells. The mesenchymal cells may also become fibroblastoid cells. These findings suggest that mesothelioma originates from mesenchymal cells.}, } @article {pmid2156241, year = {1990}, author = {Friemann, J and Müller, KM and Pott, F}, title = {Mesothelial proliferation due to asbestos and man-made fibres. Experimental studies on rat omentum.}, journal = {Pathology, research and practice}, volume = {186}, number = {1}, pages = {117-123}, doi = {10.1016/S0344-0338(11)81019-8}, pmid = {2156241}, issn = {0344-0338}, mesh = {Animals ; Asbestos/administration & dosage/*adverse effects ; Carcinogenicity Tests ; Cell Division/drug effects ; Dose-Response Relationship, Drug ; Female ; Fibrosis ; Injections, Intraperitoneal ; Mesothelioma/*etiology/pathology ; Omentum/*pathology ; Peritoneal Neoplasms/*etiology/pathology ; Polymers/administration & dosage/*adverse effects ; Rats ; Rats, Inbred Strains ; Silicon Dioxide/administration & dosage/*adverse effects ; }, abstract = {The intraperitoneal test in rats has proven to be an appropriate method controlling fibrogenicity and carcinogenicity of asbestos fibres and other fibrous dusts. We analyzed the reaction patterns of mesothelial cover layer to different natural mineral fibres (crocidolite, chrysotile, actinolite, erionite, wollastonite) and man-made mineral and synthetic fibres (glass fibres 104/475, polypropylene, aramide fibres). The injection of doses between 0.01 and 100 mg dust suspended in saline solution led to a continued repairing proliferation of submesothelial connective tissue cells and focal submesothelial fibrosis. These changes were never observed after application of granular dusts as mine dust and quartz. After 15 to 28 months we often found an association of fibrosis and local reactive hyperplasia of partly atypical proliferation of rat omentum mesothelium. These changes were also demonstrated in cases without macroscopically visible tumors. In later stages the underlying fibrosis was often infiltrated and dissolved by mesotheliomas.}, } @article {pmid2155636, year = {1990}, author = {Hill, RJ and Edwards, RE and Carthew, P}, title = {Early changes in the pleural mesothelium following intrapleural inoculation of the mineral fibre erionite and the subsequent development of mesotheliomas.}, journal = {Journal of experimental pathology (Oxford, England)}, volume = {71}, number = {1}, pages = {105-118}, pmid = {2155636}, issn = {0958-4625}, mesh = {Aluminum Silicates/*adverse effects ; Animals ; Dose-Response Relationship, Drug ; Epithelium/pathology ; Male ; Mesothelioma/*etiology/pathology ; Pleura/*pathology ; Pleural Neoplasms/*etiology/pathology ; Pleurisy/etiology/pathology ; Rats ; Zeolites ; }, abstract = {Changes in the pleura of rat lungs after intrapleural inoculation of the fibrous zeolite, erionite, have been examined from the earliest stages of reaction through to the eventual development of mesotheliomas. The initial changes involve haemorrhaging and pleural inflammation and proliferation with localized destruction of the elastic membrane under the visceral pleura. This allows cell proliferation into the lung parenchyma with fibres being able to penetrate into the lung. The chronic stimulation of the pleura by erionite eventually leads to the development of mesotheliomas which are invasive or compressing. The tumours are derived from the epithelial cells of the mesothelium (as shown by cytokeratin staining) or the subserosal cells beneath the mesothelium. Both types of mesothelioma can be invasive and some show an unusual property of 'tracking' along the blood vessels in the parenchyma as they invade. In dose-response terms for mesothelioma formation, erionite is over 200 times more tumourogenic than crocidolite (blue) asbestos.}, } @article {pmid2153537, year = {1990}, author = {Schneider, T and Skotte, J}, title = {Fiber exposure reassessed with the new indices.}, journal = {Environmental research}, volume = {51}, number = {1}, pages = {108-116}, doi = {10.1016/s0013-9351(05)80187-2}, pmid = {2153537}, issn = {0013-9351}, mesh = {Asbestos/*analysis ; Asbestos, Amosite ; Asbestos, Crocidolite ; Asbestos, Serpentine ; Asbestosis/etiology ; *Environmental Exposure ; Environmental Monitoring/*methods ; Humans ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Microscopy, Electron ; Microscopy, Phase-Contrast ; Minerals/analysis ; Risk Factors ; }, abstract = {The concentration of airborne fibers longer than 5 microns, thinner than 3 microns, and with an aspect ratio exceeding 3 as counted by phase contrast optical microscopy is the most widely used fiber exposure index. Recently, more adequate, specific exposure indices for asbestosis, lung cancer, and mesothelioma risk have been suggested by Lippmann (1988, Environ. Res., 46, 86-106). The consequences of using these indices are examined on the basis of calculations for a broad range of theoretical and published size distributions. Optical microscopy appears to be a good predictor of the exposure indices for asbestosis and for lung cancer after scaling. Only fibers longer than about 3 microns need to be counted in a transmission electron microscope. The lung cancer index still cannot explain the large differences of risk among chrysotile exposures. Both the mesothelioma exposure index and the ratio mesothelioma to lung cancer index ranks in order of increasing risk: wollastonite, glass and mineral wool, amosite, glass microfibers, chrysotile, and crocidolite. Amosite is thus not ranked according to epidemiological evidence. Detailed size information should be made available so that the size criteria can be adjusted. It may still prove necessary to use fiber type specific concentration limits.}, } @article {pmid2153315, year = {1990}, author = {Mossman, BT and Bignon, J and Corn, M and Seaton, A and Gee, JB}, title = {Asbestos: scientific developments and implications for public policy.}, journal = {Science (New York, N.Y.)}, volume = {247}, number = {4940}, pages = {294-301}, doi = {10.1126/science.2153315}, pmid = {2153315}, issn = {0036-8075}, support = {R01 CA33501/CA/NCI NIH HHS/United States ; R01 ES03878/ES/NIEHS NIH HHS/United States ; R01 HL39469/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Asbestos/*adverse effects ; Asbestos, Amphibole ; Asbestos, Serpentine ; Asbestosis ; Chemical Phenomena ; Chemistry, Physical ; Disease Models, Animal ; Humans ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Molecular Structure ; Occupational Diseases/etiology ; *Public Policy ; Pulmonary Fibrosis/etiology ; Risk Factors ; Silicon Dioxide/adverse effects ; Smoking/adverse effects ; United States ; }, abstract = {Asbestos is a commercial term for a group of fibrous minerals often associated with the development of pulmonary interstitial fibrosis (asbestosis), lung cancer, and malignant mesothelioma in occupationally exposed individuals. The pathogenicity of different forms of asbestos varies--long, thin amphibole fibers are most pathogenic, particularly in the induction of mesothelioma. Available data do not support the concept that low-level exposure to asbestos is a health hazard in buildings and schools. The concentration of asbestos fibers in air, type of asbestos, and size of fibers must be considered in evaluation of potential health risks.}, } @article {pmid2295052, year = {1990}, author = {Daya, D and McCaughey, WT}, title = {Well-differentiated papillary mesothelioma of the peritoneum. A clinicopathologic study of 22 cases.}, journal = {Cancer}, volume = {65}, number = {2}, pages = {292-296}, doi = {10.1002/1097-0142(19900115)65:2<292::aid-cncr2820650218>3.0.co;2-w}, pmid = {2295052}, issn = {0008-543X}, mesh = {Adult ; Aged ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Male ; Mesothelioma/*pathology/therapy ; Middle Aged ; Peritoneal Neoplasms/*pathology/therapy ; Prognosis ; }, abstract = {Twenty-two cases of well-differentiated papillary mesothelioma of the peritoneum (WDPMP) are described. Eighteen of the 22 patients were women. The peritoneal tumor was usually multifocal. Many of the tumors appear to be indolent or inactive and for practical purposes are benign. However, a few patients receiving adjuvant therapy have died under circumstances that make it difficult to determine whether the tumor was responsible for the death. It is suggested that adjuvant therapy be withheld from patients with WDPMP, unless there is clear evidence of progression. The cause of these rare tumors is not apparent, although three patients had had possible exposure to asbestos and two were sisters.}, } @article {pmid2379849, year = {1990}, author = {Pylev, LN and Kurliandskiĭ, BA and Nevzorova, NI and Kulagina, TF}, title = {[Possibilities of the use of the dose-response relationship in the prognostication of MPEL of carcinogenic aerosols (for instance, asbestos)].}, journal = {Gigiena truda i professional'nye zabolevaniia}, volume = {}, number = {5}, pages = {35-39}, pmid = {2379849}, issn = {0016-9919}, mesh = {Aerosols ; Animals ; Asbestos/administration & dosage/*adverse effects ; Cricetinae ; Dose-Response Relationship, Drug ; Female ; Injections ; Lung Neoplasms/*etiology ; Male ; Mesocricetus ; Mesothelioma/*etiology ; Pleura ; Pleural Neoplasms/*etiology ; Rats ; Time Factors ; Trachea ; }, } @article {pmid2325392, year = {1990}, author = {Gillis, CR and Hole, DJ and Lamont, DW}, title = {Incidence of mesothelioma in Glasgow 1981-1984.}, journal = {The Journal of the Society of Occupational Medicine}, volume = {40}, number = {1}, pages = {5-10}, doi = {10.1093/occmed/40.1.5}, pmid = {2325392}, issn = {0301-0023}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestosis/epidemiology ; Female ; Humans ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Risk Factors ; Scotland/epidemiology ; Ships ; }, abstract = {Considerable public concern exists about the effects of exposure to asbestos both at the workplace and in the general environment. In addition, the recording of mesothelioma in health registers is questionable both in terms of accuracy and completeness. This paper compares nine different sources of data for mesothelioma in an attempt to establish the true incidence of the disease in the geographical area of the Greater Glasgow Health Board between 1981 and 1984. Although 113 cases were identified, no single source identified more than 86 per cent of this total, thus presenting a case for a special mesothelioma register. A questionnaire-based study of the occupational exposures and residential histories of the cases was also carried out. It confirmed the findings of similar studies in that mesothelioma occurs predominantly in those exposed by reason of their occupation. No relationship with place of residence was apparent independent of occupation.}, } @article {pmid2316372, year = {1990}, author = {Horie, A and Hiraoka, K and Yamamoto, O and Haratake, J and Tsuchiya, T and Sugimoto, H}, title = {An autopsy case of peritoneal malignant mesothelioma in a radiation technologist.}, journal = {Acta pathologica japonica}, volume = {40}, number = {1}, pages = {57-62}, doi = {10.1111/j.1440-1827.1990.tb01529.x}, pmid = {2316372}, issn = {0001-6632}, mesh = {Autopsy ; Humans ; Male ; Mesothelioma/etiology/*pathology/ultrastructure ; Microscopy, Electron ; Middle Aged ; Neoplasms, Radiation-Induced/pathology/ultrastructure ; Occupational Diseases/etiology/*pathology ; Peritoneal Cavity/pathology/radiation effects ; Peritoneal Neoplasms/etiology/*pathology/ultrastructure ; Radiation Injuries ; }, abstract = {A case of peritoneal malignant mesothelioma in a radiation technologist, who had worked in this field for 34 years, is reported. Histopathologically, a biopsy specimen from the retroperitoneal tumor revealed a biphasic type of malignant mesothelioma. Electron microscopy disclosed that the tumor cells contained prominent microvilli, basal laminae adjacent to the stroma, junctional complexes, desmosomes, tonofilaments, clusters of glycogen granules, well developed rough endoplasmic reticulum (RER), confronting cisternae showing direct continuity with the RER and membrane-bound granules suggestive of secretory activity. No increased amount of asbestos was detected in autopsied lung material or the peritoneal mesothelioma. The estimated cumulative dose of occupational irradiation was calculated to be about 40 to 50 rad at most. Irradiation was discussed in relation to the etiology of the peritoneal mesothelioma.}, } @article {pmid2315277, year = {1990}, author = {Rüttner, JR and Wälchli, P and Vogt, P and Christen, B}, title = {[Asbestos types, lung dust analysis, exposure and latency time of malignant mesotheliomas in German Switzerland].}, journal = {Der Pathologe}, volume = {11}, number = {1}, pages = {25-30}, pmid = {2315277}, issn = {0172-8113}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects/classification ; Asbestosis/*pathology ; Dust/*adverse effects ; Female ; Follow-Up Studies ; Humans ; Male ; Mesothelioma/*pathology ; Middle Aged ; Peritoneal Neoplasms/*pathology ; Peritoneum/pathology ; Pleura/pathology ; Pleural Neoplasms/*pathology ; Risk Factors ; }, } @article {pmid2310711, year = {1990}, author = {Huncharek, M and Muscat, J}, title = {Pleural mesothelioma in a non-shipyard electrician.}, journal = {British journal of industrial medicine}, volume = {47}, number = {1}, pages = {68}, pmid = {2310711}, issn = {0007-1072}, mesh = {Adult ; Asbestos/*adverse effects ; *Electricity ; Humans ; Male ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; Pleural Neoplasms/*etiology ; }, } @article {pmid2274714, year = {1990}, author = {Corrin, B and Addis, BJ}, title = {Histopathology of the pleura.}, journal = {Respiration; international review of thoracic diseases}, volume = {57}, number = {3}, pages = {160-175}, doi = {10.1159/000195839}, pmid = {2274714}, issn = {0025-7931}, mesh = {Humans ; Pleura/*pathology/physiopathology ; Pleural Diseases/*pathology ; Pleural Neoplasms/pathology ; }, abstract = {This review attempts to provide up to date information on structure/function relationships of the pleura and on the pathology of pleural effusions, pneumothorax, pleural repair, pleural infections, pleural involvement in systemic connective tissue disorders, non-malignant asbestos-induced pleural disease, mesothelioma and other pleural tumours.}, } @article {pmid2264653, year = {1990}, author = {Seidman, H and Selikoff, IJ}, title = {Decline in death rates among asbestos insulation workers 1967-1986 associated with diminution of work exposure to asbestos.}, journal = {Annals of the New York Academy of Sciences}, volume = {609}, number = {}, pages = {300-17; discussion 317-8}, doi = {10.1111/j.1749-6632.1990.tb32077.x}, pmid = {2264653}, issn = {0077-8923}, mesh = {Adolescent ; Adult ; Aged ; Asbestos/*adverse effects ; Asbestosis/mortality ; Canada/epidemiology ; Cause of Death ; Cohort Studies ; Environmental Exposure ; Humans ; Lung Neoplasms/mortality ; Mesothelioma/mortality ; Middle Aged ; Mortality/trends ; Occupational Diseases/etiology/*mortality/prevention & control ; Peritoneal Neoplasms/mortality ; United States/epidemiology ; }, } @article {pmid2237087, year = {1990}, author = {Rusch, VW}, title = {Diagnosis and treatment of pleural mesothelioma.}, journal = {Seminars in surgical oncology}, volume = {6}, number = {5}, pages = {279-285}, doi = {10.1002/ssu.2980060510}, pmid = {2237087}, issn = {8756-0437}, mesh = {Combined Modality Therapy ; Humans ; Mesothelioma/mortality/pathology/*therapy ; Neoplasm Staging ; Pleural Neoplasms/mortality/pathology/*therapy ; }, abstract = {Pleural mesotheliomas are uncommon tumors. They can be broadly classified as localized and diffuse. The localized form is a non-epithelial neoplasm that occurs as commonly in women as in men and is not related to asbestos exposure. It is usually asymptomatic, and is occasionally associated with paraneoplastic syndromes. Localized mesotheliomas arise more frequently from the visceral than from the parietal or mediastinal pleura. The long-term outcome of these tumors is determined mainly by their clinical presentation, and by whether or not they can be completely resected. Diffuse pleural mesotheliomas are invariably malignant. They are clearly related to asbestos exposure, and are far more common in men than in women. Histologically, they are completely or partially epithelial tumors. Diffuse mesotheliomas present with dyspnea, chest pain, and weight loss and are not associated with paraneoplastic syndromes. Distinguishing malignant mesothelioma from metastatic adenocarcinoma can be difficult and usually requires a large tissue biopsy on which immunohistochemistry and electron microscopy can be performed. The management of diffuse malignant mesothelioma remains controversial. Treatment appears to prolong survival which ranges from 6 to 12 months with supportive care alone. Surgical resection, either with extrapleural pneumonectomy or by pleurectomy/decortications remains the mainstay of treatment because of the relative ineffectiveness of radiation and chemotherapy. Surgical resection alone, however, is inadequate, so most current treatment regimens combine operation with radiation and/or chemotherapy. Even with aggressive multimodality treatment, the median survival currently ranges from 18 to 24 months. A better understanding of prognostic factors, a better staging system, and innovative treatment strategies are desperately needed in this disease.}, } @article {pmid2236871, year = {1990}, author = {McDonald, JC}, title = {Cancer risks due to asbestos and man-made fibres.}, journal = {Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer}, volume = {120}, number = {}, pages = {122-131}, doi = {10.1007/978-3-642-84068-5_9}, pmid = {2236871}, issn = {0080-0015}, mesh = {Asbestos/*adverse effects ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; Prevalence ; Risk Factors ; *Textiles ; }, } @article {pmid2218292, year = {1990}, author = {Larrouy, C and Tandjaoui-Lambiotte, H and Mellat, M and Fabre, C and Defrejacques, C and Adotti, F and Piquet, J}, title = {[Environmental interstitial pneumonia caused by asbestos. Study of a Turkish family exposed to tremolite].}, journal = {Revue de pneumologie clinique}, volume = {46}, number = {2}, pages = {78-82}, pmid = {2218292}, issn = {0761-8417}, mesh = {Asbestos/*adverse effects ; *Asbestos, Amphibole ; Bronchoalveolar Lavage Fluid/chemistry ; Environmental Exposure ; Female ; Humans ; Middle Aged ; Pedigree ; Pulmonary Fibrosis/diagnostic imaging/*etiology/genetics ; Silicic Acid/adverse effects ; Tomography, X-Ray Computed ; Turkey ; }, abstract = {Environmental exposure to asbestos, as observed in Anatolia (Turkey), usually results in pleural pathology (plaques and mesothelioma). We report the case of a 50-year old woman who, until the age of 50, had lived in Eregli, central Anatolia, a region where inhalation of environmental asbestos is responsible for a high prevalence of pleural diseases. Radiology showed diffuse interstitial pneumonia without pleural involvement. Bronchoalveolar lavage brought back asbestos bodies (AB) in concentrations of 4,250 per millilitre. All were made of tremolite, a non-commercial variety of asbestos. The patient's family was investigated by chest radiography and search for AB in sputum. The husband, who came from the same town as his wife and had been exposed until the age of 45, had the classical response with bilateral pleural thickening but no parenchymal abnormalities; 2 AB were found in his sputum. The 3 sons, exposed for 10, 13 and 20 years respectively, had normal radiograms and no AB in their sputum, except for the older (3 AB) who had been exposed for 20 years. These cases illustrate the importance of environmental exposure to asbestos which may produce lesions similar to those observed in industrial exposure. Only mineralogical examinations can determine whether the asbestos is environmental or industrial.}, } @article {pmid2203959, year = {1990}, author = {Brown, RC and Hoskins, JA and Miller, K and Mossman, BT}, title = {Pathogenetic mechanisms of asbestos and other mineral fibres.}, journal = {Molecular aspects of medicine}, volume = {11}, number = {5}, pages = {325-349}, doi = {10.1016/0098-2997(90)90002-j}, pmid = {2203959}, issn = {0098-2997}, support = {R0I HL3969/HL/NHLBI NIH HHS/United States ; SCOR 14212/SC/NCI NIH HHS/United States ; }, mesh = {Asbestos/*adverse effects ; Chemical Phenomena ; Chemistry ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Molecular Conformation ; Pulmonary Fibrosis/*etiology ; }, } @article {pmid2175726, year = {1990}, author = {Nikitina, OV and Troitskaia, NA and Kogan, FM and Velichkovskiĭ, BT and Blokhin, VA and Kuznetsova, ZM and Vanchugova, NN}, title = {[Hygienic aspects of the production of asbestos substitutes].}, journal = {Gigiena truda i professional'nye zabolevaniia}, volume = {}, number = {9}, pages = {30-34}, pmid = {2175726}, issn = {0016-9919}, mesh = {Asbestos/*adverse effects ; Asbestos, Serpentine ; Carbon/*adverse effects ; Carbon Fiber ; Dust/adverse effects ; Humans ; Microclimate ; Minerals/*adverse effects ; Occupational Diseases/*etiology/prevention & control ; *Silicates ; Silicon Dioxide/*adverse effects ; }, abstract = {Due to the high level aggressiveness of asbestos, more attempts have been made in the recent years to replace asbestos by other artificial mineral fibres. In this connection, the labour conditions were studied in the basalt and carbon fibres processing sites. The major occupational hazards of these sites included basalt and carbon fibres dusts, heating microclimate in some working zones and physical overload. An intratracheal experiment revealed a lower degree of fibrinogenicity of the basalt and carbon fibres as compared to chrysotile asbestos. The number of the induced mesothelioma in the intraperitoneal introduction of basalt and carbon fibres was markedly lower than in case with chrysotile asbestos. Hygienically, asbestos should be replaced wherever possible, and the dust control measures should by no means be inferior to those with asbestos.}, } @article {pmid2158231, year = {1990}, author = {Churg, A and Green, F}, title = {Re: Mesothelioma in railroad machinists.}, journal = {American journal of industrial medicine}, volume = {17}, number = {4}, pages = {523-530}, doi = {10.1002/ajim.4700170410}, pmid = {2158231}, issn = {0271-3586}, mesh = {Asbestos/*adverse effects ; Asbestos, Serpentine ; Asbestosis/*etiology ; Humans ; Mesothelioma/*etiology ; Pleural Neoplasms/*etiology ; *Railroads ; Risk Factors ; }, } @article {pmid2155646, year = {1990}, author = {Otte, KE and Sigsgaard, TI and Kjaerulff, J}, title = {Malignant mesothelioma: clustering in a family producing asbestos cement in their home.}, journal = {British journal of industrial medicine}, volume = {47}, number = {1}, pages = {10-13}, pmid = {2155646}, issn = {0007-1072}, mesh = {Aged ; Asbestos/*adverse effects ; Asbestos, Amosite ; Cluster Analysis ; Denmark ; *Family ; *Family Health ; Female ; Humans ; Male ; Mesothelioma/*etiology ; Middle Aged ; Occupational Diseases/*etiology ; Peritoneal Neoplasms/*etiology ; Pleural Neoplasms/*etiology ; }, abstract = {In a family with a remarkable aggregation of malignant mesothelioma the father, mother, and a son all died of the condition, whereas two other sons and a daughter were unaffected. From 1944 to 1961 the family produced a material that was used to fix screws in drilled holes and consisted of amosite, gypsum, and sand. It was produced in the basement of their villa and was described as being a dusty job. The father died in 1984 aged 74, the son in 1985 aged 45, and the mother in 1987 aged 79. It is concluded that there is a high risk of malignant mesothelioma after massive exposure to amosite and the risk and latency period are independent of age during the exposure.}, } @article {pmid2139623, year = {1990}, author = {Iatsenko, AS and Kogan, FM}, title = {[Occupational morbidity and mortality in malignant neoplasms among persons professionally exposed to asbestos dust].}, journal = {Gigiena truda i professional'nye zabolevaniia}, volume = {}, number = {2}, pages = {10-12}, pmid = {2139623}, issn = {0016-9919}, mesh = {Air Pollutants, Occupational/*adverse effects ; Asbestos/*adverse effects ; Cohort Studies ; Dust/adverse effects ; Female ; Humans ; Lung Neoplasms/*epidemiology/etiology/mortality ; Male ; Mesothelioma/*epidemiology/etiology/mortality ; Pleural Neoplasms/*epidemiology/etiology/mortality ; Russia ; }, abstract = {Asbestos fibres discharged as a result of machine processing of brakes, are characterized by a lowered biological activity due to the fixation layer which covers them. This has been confirmed through occupational diseases' analysis and new data on malignant neoplasms epidemiology among workers engaged in machine processing of asbestos-moulded machine parts. General mortality caused by malignant neoplasms in these groups higher than in the control group, although statistically is not significant. This necessitates further epidemiologic studies to be performed at similar plants.}, } @article {pmid2132039, year = {1990}, author = {Vayre, P and Guntz, M and Jost, JL and Koulibaly, M and Chomette, G}, title = {[Peritoneal mesothelioma].}, journal = {Chirurgie; memoires de l'Academie de chirurgie}, volume = {116}, number = {10}, pages = {866-872}, pmid = {2132039}, issn = {0001-4001}, mesh = {Adolescent ; Adult ; Aged ; Female ; Humans ; Male ; *Mesothelioma/diagnosis/pathology/therapy ; Middle Aged ; *Peritoneal Neoplasms/diagnosis/pathology/therapy ; }, abstract = {On the basis of 5 personal cases with illustrations and a review of the literature, the authors emphasize the clinicopathological features of peritoneal mesotheliomas, rare primary tumors for which the histological diagnosis is often difficult. The classical evidence by contact with asbestos fibers is obtained in every second case only. The tumor is often associated with a pleural lesion. Ultrasound and CT currently aid in the diagnosis, usually in a context of extensive ascites. The prognosis is poor. For technical reasons, surgical exeresis most often remains partial in the diffuse forms. Chemotherapy is rarely effective.}, } @article {pmid2593905, year = {1989}, author = {de Klerk, NH and Armstrong, BK and Musk, AW and Hobbs, MS}, title = {Predictions of future cases of asbestos-related disease among former miners and millers of crocidolite in Western Australia.}, journal = {The Medical journal of Australia}, volume = {151}, number = {11-12}, pages = {616-620}, doi = {10.5694/j.1326-5377.1989.tb139629.x}, pmid = {2593905}, issn = {0025-729X}, mesh = {Adult ; Asbestosis/*epidemiology/mortality ; Cohort Studies ; Female ; Forecasting ; Humans ; Lung Neoplasms/*epidemiology/mortality ; Male ; Mesothelioma/*epidemiology/mortality ; Middle Aged ; Western Australia ; }, abstract = {In a cohort of 6502 male and 410 female former workers from the crocidolite (blue asbestos) mining and milling works at Wittenoom, Western Australia, there were 94 cases of malignant mesothelioma (12 cases of peritoneal mesothelioma), 141 cases of lung cancer and 356 successful compensation claims for asbestosis to the end of 1986. After adjusting for measured covariate effects by means of proportional hazards regression analysis, smooth curves were fitted to the resulting "underlying" incidence rates for malignant mesothelioma, lung cancer and asbestosis, separately, and for mortality of any cause. By the use of these curves and individual risk estimates, predictions have been made of the future incidence of these diseases to the year 2020. With the assumption that all subjects who were not known to be dead or departed overseas still were alive at December 31, 1986, and excluding persons of more than 85 years of age, the number of new cases of mesothelioma is expected to rise to a peak of around 25 cases per year in 2010, with an expected total number of 692 cases of mesothelioma (95% confidence interval [CI], 394-990 cases) between 1987 and 2020. A total of 2898 deaths (95% CI, 2284-3511 deaths) of any cause is expected in the same period. New cases of lung cancer and asbestosis are expected to continue at roughly the current rates of eight and 17 cases per year, respectively, before declining after the year 2000, leading to totals of 183 cases (95% CI, 34-335 cases) and 482 cases (95% CI, 236-728 cases), respectively, being expected by the year 2020. Predictions that were based on the censoring of subjects at the date that they last were known to be alive resulted in slightly higher, but probably less accurate, estimates.}, } @article {pmid2635002, year = {1989}, author = {Kilpatrick, DJ}, title = {Pleural mesothelioma in a lift mechanic.}, journal = {British journal of industrial medicine}, volume = {46}, number = {12}, pages = {894}, doi = {10.1136/oem.46.12.894}, pmid = {2635002}, issn = {0007-1072}, mesh = {Asbestos/*adverse effects ; Humans ; Male ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; Pleural Neoplasms/*etiology ; }, } @article {pmid2617262, year = {1989}, author = {Schüler, G and Rüttner, JR}, title = {Mesothelioma among Swiss furniture workers.}, journal = {Scandinavian journal of work, environment & health}, volume = {15}, number = {6}, pages = {440-442}, doi = {10.5271/sjweh.1827}, pmid = {2617262}, issn = {0355-3140}, mesh = {Asbestos/*adverse effects ; Humans ; Interior Design and Furnishings ; Mesothelioma/*chemically induced/epidemiology ; Occupational Diseases/*chemically induced/epidemiology ; Pleural Neoplasms/*chemically induced/epidemiology ; Switzerland/epidemiology ; }, } @article {pmid2617261, year = {1989}, author = {Merler, E and Ricci, P}, title = {Re: "Malignant Pleural Mesothelioma Among Swiss Furniture Workers: A New High-Risk Group" by CE Minder, J.P Vader. Scand J work Environ Health 1988;14:252-6.}, journal = {Scandinavian journal of work, environment & health}, volume = {15}, number = {6}, pages = {439-440}, doi = {10.5271/sjweh.1828}, pmid = {2617261}, issn = {0355-3140}, mesh = {Asbestos/adverse effects ; Humans ; Interior Design and Furnishings ; Male ; Mesothelioma/*chemically induced ; Occupational Diseases/*chemically induced ; Pleural Neoplasms/*chemically induced ; Risk Factors ; Switzerland ; }, } @article {pmid2617255, year = {1989}, author = {Melkild, A and Langård, S and Andersen, A and Tønnessen, JN}, title = {Incidence of cancer among welders and other workers in a Norwegian shipyard.}, journal = {Scandinavian journal of work, environment & health}, volume = {15}, number = {6}, pages = {387-394}, doi = {10.5271/sjweh.1834}, pmid = {2617255}, issn = {0355-3140}, mesh = {Air Pollutants, Occupational/adverse effects ; Asbestos/adverse effects ; Female ; Humans ; Lung Neoplasms/chemically induced/*epidemiology ; Male ; Mesothelioma/chemically induced/*epidemiology ; Norway/epidemiology ; Occupational Diseases/chemically induced/*epidemiology ; Ships ; Urinary Bladder Neoplasms/chemically induced/*epidemiology ; Welding ; }, abstract = {The incidence of cancer among 4778 male shipyard workers, including 783 mild steel welders, was investigated in a historical cohort study. The workers had been employed for at least three months between 1 January 1946 and 31 March 1977. The incidence of cancer was observed from 1 January 1953 through 1986. The loss during follow-up was only 0.9%. There were 53 observed cases of lung cancer in the whole cohort versus 31.3 expected on the basis of the national rates for men. There was an increased incidence of lung cancer among the welders, with seven observed cases versus 3.2 expected. Twenty-two cases of bladder cancer were observed versus 15.2 expected. Two malignant mesotheliomas had occurred (0.7 expected). Smoking was likely to be a confounder in the present study. Due to concomitant exposure to asbestos, the results are inconclusive concerning the possible relationship between exposure to welding fumes and lung cancer.}, } @article {pmid2552314, year = {1989}, author = {Talcott, JA and Thurber, WA and Kantor, AF and Gaensler, EA and Danahy, JF and Antman, KH and Li, FP}, title = {Asbestos-associated diseases in a cohort of cigarette-filter workers.}, journal = {The New England journal of medicine}, volume = {321}, number = {18}, pages = {1220-1223}, doi = {10.1056/NEJM198911023211803}, pmid = {2552314}, issn = {0028-4793}, support = {1F32CA08242/CA/NCI NIH HHS/United States ; HL1173/HL/NHLBI NIH HHS/United States ; }, mesh = {Asbestos/*poisoning ; Asbestos, Crocidolite ; Asbestosis/epidemiology/*etiology/mortality ; Cohort Studies ; Humans ; Lung Neoplasms/epidemiology/etiology ; Male ; Massachusetts/epidemiology ; Mesothelioma/epidemiology/etiology ; Occupational Diseases/epidemiology/etiology ; Plants, Toxic ; Nicotiana ; }, abstract = {To estimate the effects on health of occupational exposure to crocidolite, a highly toxic form of asbestos, we studied a cohort of 33 men who worked in 1953 in a Massachusetts factory that manufactured cigarette filters containing crocidolite fibers from 1951 to 1957. Twenty-eight of the men have died, as compared with 8.3 deaths expected. This increased mortality was attributable to asbestos-associated diseases. Fifteen deaths were caused by cancer, as compared with 1.8 expected (relative risk, 8.2; 95 percent confidence interval, 4.6 to 13.4), including eight from lung cancer, five from malignant mesothelioma, and two from other types of cancer. There were seven deaths from nonmalignant respiratory disease, as compared with 0.5 expected (relative risk, 14.7; 95 percent confidence interval, 5.9 to 30.3), of which five were due primarily to asbestosis. In contrast, the mortality rates from cardiovascular diseases and all other causes were not increased. Four of the five living workers have pulmonary asbestosis; three of them have recently diagnosed cancers, including two additional lung cancers. We conclude that the extremely high morbidity and mortality in these workers were caused by intense exposure to crocidolite asbestos fibers.}, } @article {pmid2688171, year = {1989}, author = {Rüegger, M}, title = {[Occupationally-induced pneumopathies].}, journal = {Therapeutische Umschau. Revue therapeutique}, volume = {46}, number = {11}, pages = {789-795}, pmid = {2688171}, issn = {0040-5930}, mesh = {Alveolitis, Extrinsic Allergic/etiology ; Asthma/etiology ; Humans ; Lung Diseases/*etiology ; Occupational Diseases/*etiology ; Pneumoconiosis/etiology ; }, abstract = {Today chronic obstructive airways diseases rank amongst the most important occupational pneumopathies in Switzerland. As far as asthma is concerned, the baker's (flour) and the spray painter's (Isocyanates) types are the most important. Despite their frequent occurrence the two forms of asthma seem to differ in their pathogenetic mechanisms. Due to technical precautions another type of occupational pneumopathology namely pneumoconiosis was considerably reduced. Among asbestos induced diseases the cases of asbestosis are decreasing. However, there still are quite a lot of events of malignant mesotheliomas actually heading the list of occupational malignomas. The most numerous asbestos induced disturbances, however, are pleural plaques which seem to be of no considerable importance. Another group of occupational lung disorders is that of hypersensitivity pneumonitis (extrinsic allergic alveolitis), among which the "farmer's lung" and in more industrial settings the "humidifier lung" are most frequently seen. For the diagnosis and evaluation of occupational pneumopathies work related symptoms and individual work place exposure are of decisive importance.}, } @article {pmid2687807, year = {1989}, author = {Knudsen, N and Block, K and Schulman, S}, title = {Malignant pleural mesothelioma.}, journal = {Oncology nursing forum}, volume = {16}, number = {6}, pages = {845-851}, pmid = {2687807}, issn = {0190-535X}, support = {CA 34408/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Mesothelioma/etiology/*nursing/therapy ; Pleural Neoplasms/etiology/*nursing/therapy ; Risk Factors ; }, abstract = {Malignant pleural mesotheliomas are tumors originating in the serosal lining of the pleural cavities. Although these are relatively rare tumors, an increasing number of cases are anticipated over the next decade. Patients with these tumors, which are almost invariably fatal, usually have an interval of less than two years between the onset of symptoms and death. There is a well established link between mesothelioma and asbestos exposure. Treatment includes surgery, chemotherapy, and radiotherapy. This article explores the epidemiology and etiology of the disease, offers a summary of current treatment options, and discusses nursing strategies.}, } @article {pmid2618661, year = {1989}, author = {Fukuda, T and Ishikawa, H and Ohnishi, Y and Tachikawa, S and Oguma, F and Kasuya, S and Sakashita, I}, title = {Malignant spindle cell tumor of the pericardium. Evidence of sarcomatous mesothelioma with aberrant antigen expression.}, journal = {Acta pathologica japonica}, volume = {39}, number = {11}, pages = {750-754}, pmid = {2618661}, issn = {0001-6632}, mesh = {Female ; Heart Neoplasms/analysis/*pathology/ultrastructure ; Humans ; Immunohistochemistry ; Mesothelioma/analysis/*pathology/ultrastructure ; Middle Aged ; Pericardium/analysis/*pathology ; }, abstract = {A case of malignant spindle cell tumor occurring in the pericardium is presented. The tumor arose from the pericardium of a 51-year-old Japanese woman with no history of exposure to asbestos. The tumor extended into the pericardial and left pleural cavities. The primary and metastatic tumors consisted of fusiform cells with frequent mitoses. Ultrastructurally, the tumor cells possessed a discontinuous external lamina, cytoplasmic processes, microfilaments and desmosomal intercellular junctions. Immunohistochemical examination showed that most tumor cells were positive for Leu 7, and several for S-100 and glial fibrillary acidic protein. Unexpectedly, most of the tumor cells also expressed keratin. These findings favor a diagnosis of sarcomatous mesothelioma with aberrant antigenic expression or heterogeneous differentiation of neoplastic cells.}, } @article {pmid2611743, year = {1989}, author = {Egedahl, RD and Olsen, GW and Coppock, E and Young, ML and Arnold, IM}, title = {An historical prospective mortality study of the Sarnia Division of Dow Chemical Canada Inc., Sarnia, Ontario (1950-1984).}, journal = {Canadian journal of public health = Revue canadienne de sante publique}, volume = {80}, number = {6}, pages = {441-446}, pmid = {2611743}, issn = {0008-4263}, mesh = {Adult ; Canada ; *Cause of Death ; *Chemical Industry ; Healthy Worker Effect ; Humans ; Information Systems ; Male ; Middle Aged ; Occupational Diseases/epidemiology/*mortality ; Prospective Studies ; }, abstract = {We examined the mortality experience of 3,479 male Dow Canada employees who were employed at Sarnia Division for at least 12 continuous months during the years 1945 through 1983, utilizing the Canadian Mortality Data Base maintained by Statistics Canada, covering 1950-1984. We analyzed cause-specific mortality using male, age and calendar-year-adjusted death rates for Canada and Ontario. Total mortality was significantly below expectation whether the entire follow-up period (240 observed vs. 366.9 expected) or a 15-year latency period (171 observed vs. 290.4 expected) was considered. Statistically significant fewer observed deaths were found for all respiratory cancer, cancer of the bronchus and lung, circulatory disease, ischemic heart disease, cerebrovascular disease, digestive disease, cirrhosis and other liver disease and deaths due to accidents, poisonings and violence. The observation of three deaths due to mesothelioma, a rare cancer often associated with asbestos exposure, was a significant finding as was a statistically significant elevation of observed deaths in the category "other forms of heart disease".}, } @article {pmid2608642, year = {1989}, author = {Schildge, J and Kaiser, D and Henss, H and Fiebig, H and Ortlieb, H}, title = {[Prognostic factors in diffuse malignant mesothelioma of the pleura].}, journal = {Pneumologie (Stuttgart, Germany)}, volume = {43}, number = {11}, pages = {660-664}, pmid = {2608642}, issn = {0934-8387}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Mesothelioma/*pathology ; Middle Aged ; Neoplasm Staging ; Pleural Neoplasms/*pathology ; Prognosis ; }, abstract = {Diffuse malignant pleural mesothelioma (DMM) is associated with a very poor prognosis and is only partially accessible to treatment. On the basis of a retrospective analysis, we made an attempt to identify possible factors that influence the prognosis. Between 1964 and 1986, 84 evaluable patients were treated: the ratio of male to female patients was 4.3:1, their average age being 58.5 +/- 11.9 (range: 21-82 years). The tumour types included 50% epithelial, 38% biphasic, and 12% mesenchymal tumours. The classification in accordance with the suggestions of Butchart revealed: I 10%, II 89%, III 0%, IV 1%. In 32% of the patients, treatment was purely symptomatic, in 42% a palliative surgical procedure with decortication of the tumour and tumour-pleurectomy was performed, while in 26% the palliative procedure was followed by adjuvant chemotherapy using doxorubicin and cisplatin. The median survival for the patients overall was 253 days. Parameters that were found not to correlate with the prognosis were: age, sex, exposure to asbestos, use of tobacco, pleural effusion, and growth behaviour in the thymus aplastic nude mouse. A significant influence was found for the histological type of the tumour and therapy administered, epithelial and biphasic tumour forms, as also surgical and combined surgical/chemotherapeutic treatment resulting in a more prolonged survival. On the basis of these results, surgical therapy should always be employed, despite the fact that there is almost always no curative option; postoperative adjuvant therapy is capable of further improving the prognosis.}, } @article {pmid2606200, year = {1989}, author = {van Gelder, T and Hoogsteden, HC and Versnel, MA and van Hezik, EJ and Vandenbroucke, JP and Planteydt, HT}, title = {Malignant pleural mesothelioma in the southwestern part of The Netherlands.}, journal = {The European respiratory journal}, volume = {2}, number = {10}, pages = {981-984}, pmid = {2606200}, issn = {0903-1936}, mesh = {Aged ; Asbestos/*adverse effects ; Female ; Humans ; Male ; Mesothelioma/*epidemiology/etiology ; Netherlands/epidemiology ; Occupational Diseases/*epidemiology/etiology ; Pleural Neoplasms/*epidemiology/etiology ; Time Factors ; }, abstract = {This report is the result of an analysis of the medical records of 124 patients presenting with a malignant pleural mesothelioma. Information about asbestos exposure was available in 104 of them, which appeared to be positive in 95 (91%). The median duration of exposure was 34 yrs. The median latent period was 41 yrs. The median survival was 11 months while different ways of treatment could not prolong survival. The most common radiologic findings were pleural effusions, while in some patients contralateral effusions or pleural thickening was found. Pleural plaques or asbestosis were seen in a minority of the patients. In this series a relatively high percentage of mixed type mesotheliomas was found (56%). Large biopsies will often show both epithelial and connective tissue type elements. Concerning diagnostic procedures we recommend beginning with cytology of pleural fluid, which can easily be obtained together with an Abrams biopsy. If this does not give a definite diagnosis thoracoscopy or thoracotomy will be indicated.}, } @article {pmid2803935, year = {1989}, author = {Tiainen, M and Tammilehto, L and Rautonen, J and Tuomi, T and Mattson, K and Knuutila, S}, title = {Chromosomal abnormalities and their correlations with asbestos exposure and survival in patients with mesothelioma.}, journal = {British journal of cancer}, volume = {60}, number = {4}, pages = {618-626}, pmid = {2803935}, issn = {0007-0920}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; *Chromosome Aberrations ; *Chromosome Disorders ; Environmental Exposure ; Female ; Humans ; Karyotyping ; Male ; Mesothelioma/etiology/*genetics/mortality ; Middle Aged ; Pleural Neoplasms/etiology/*genetics/mortality ; }, abstract = {Cytogenetic findings of our 30 previously reported and eight new patients with malignant pleural mesothelioma were summarised and correlated with asbestos fibre burden in lung tissue and survival. Successful cytogenetic analyses were performed on cells obtained from the tumours and/or pleural effusions of 34 of the 38 patients. Clonal chromosomal abnormalities were detected in 25 patients, 19 of them studied before treatment. Nine patients, seven of them studied before treatment, had normal karyotypes and/or non-clonal chromosomal abnormalities. Most of the karyotypic findings in the patients with clonal abnormalities were complex and heterogeneous, and no chromosome aberration specific to mesothelioma could be demonstrated. The following numerical abnormalities in decreasing order of frequency were preferentially present in karyotypic changes: -22, +7, -1, -3, -9, +11 and -14 (-/+ denoting partial or total loss or gain). Translocations and deletions involving a breakpoint at 1p11-p22 were the most frequent structural aberrations. Statistically significant correlations were found between high content of asbestos fibres in lung tissue and partial or total losses of chromosomes 1 and 4, and a breakpoint at 1p11-p22 (P = 0.0001, P = 0.003, P = 0.009, respectively). The number of copies of chromosome 7 short arms was inversely correlated with survival (P = 0.02). In this study no diagnostic cytogenetic markers of mesothelioma were found, instead the copy number of chromosome 7 short arms turned out to be a possible prognostic factor in malignant mesothelioma.}, } @article {pmid2792062, year = {1989}, author = {Warnock, ML}, title = {Lung asbestos burden in shipyard and construction workers with mesothelioma: comparison with burdens in subjects with asbestosis or lung cancer.}, journal = {Environmental research}, volume = {50}, number = {1}, pages = {68-85}, doi = {10.1016/s0013-9351(89)80049-0}, pmid = {2792062}, issn = {0013-9351}, mesh = {Aged ; Aged, 80 and over ; Asbestos/*adverse effects/analysis ; Asbestosis/*etiology/pathology ; Autopsy ; Construction Materials/adverse effects/analysis ; Female ; Humans ; Lung/analysis/pathology ; Lung Neoplasms/*etiology/pathology ; Male ; Mesothelioma/*etiology/pathology ; Middle Aged ; Naval Medicine ; Occupational Diseases/chemically induced ; }, abstract = {Although mesothelioma is generally considered to be caused by asbestos, epidemiologic studies indicate that some cases have another cause. In order to determine whether pulmonary asbestos burden can be used to define asbestos-related mesotheliomas, asbestos burden was quantified in 27 shipyard or construction workers with diffuse malignant mesothelioma of the pleura or peritoneum and a history of asbestos exposure. Their burden was significantly greater than the burden found in 19 unexposed men (P less than 0.001). The burdens were also compared to those of previously reported subjects with asbestosis or lung cancer. The median concentration for total amphibole fibers (2.7 million/g dry lung) in subjects with mesothelioma did not differ significantly from our previously reported median values for 14 subjects with asbestosis (1.3 million/g dry lung) or for 60 asbestos workers with lung cancer (1.3 million/g dry lung). Fiber size distribution for amosite, the most prevalent fiber type, was similar in all three subject groups. Fifteen of 25 (60%) subjects with mesothelioma had mild asbestosis. Asbestos body (AB) concentrations were greater than or equal to 1900/g dry lung, and total amphibole fiber concentrations were greater than or equal to 390,000/g dry lung. Counts of ABs greater than or equal to 0.5/cm2 in histologic sections always signified both of these concentrations in extracts. Thus, histologic sections showing greater than or equal to 0.5 ABs/cm2 or extracts containing asbestos body or amphibole fiber concentrations of at least 1900 or 390,000/g dry lung, respectively, will confirm an asbestos-related mesothelioma.}, } @article {pmid2788546, year = {1989}, author = {Manning, LS and Bowman, RV and Davis, MR and Musk, AW and Robinson, BW}, title = {Indomethacin augments lymphokine-activated killer cell generation by patients with malignant mesothelioma.}, journal = {Clinical immunology and immunopathology}, volume = {53}, number = {1}, pages = {68-77}, doi = {10.1016/0090-1229(89)90102-5}, pmid = {2788546}, issn = {0090-1229}, mesh = {Asbestos/*adverse effects ; Cytotoxicity, Immunologic/*drug effects ; Drug Synergism ; Environmental Exposure ; Humans ; Indomethacin/*pharmacology ; Interleukin-2/pharmacology ; Killer Cells, Natural/*drug effects/immunology ; Mesothelioma/etiology/*immunology/pathology ; Occupational Diseases/*immunology/pathology ; Pleural Neoplasms/etiology/*immunology/pathology ; Prostaglandins/biosynthesis ; Tumor Cells, Cultured ; }, abstract = {Human malignant mesothelioma (MM) cells are resistant to natural killer (NK) cell lysis but susceptible to lysis by lymphokine-activated killer (LAK) cells from control individuals. The present study was performed to determine the capacity of patients with MM (n = 22) and individuals occupationally exposed to asbestos (the major population at risk of developing this disease, n = 52) to generate LAK cells capable of effectively lysing human mesothelioma cells. Compared to controls (n = 20), both patient groups demonstrated significantly depressed LAK cell activity against mesothelioma tumor cell targets (55 +/- 3% lysis by controls vs 34 +/- 3% lysis by patients with MM, P less than 0.005; and 45 +/- 3% lysis by asbestos-exposed individuals, P less than 0.025). Addition of 10 micrograms/ml indomethacin during LAK cell generation restored normal LAK cell activity for patients with MM (52 +/- 6% lysis of cultured human MM cells, P = NS compared to controls), suggesting that the defective cytolytic cell function observed in some patients with MM is a result of prostaglandin-induced immunosuppression. The ability of indomethacin to restore suppressed LAK cell activity in patients with MM suggests that the concomitant use of this agent in ex vivo LAK cell generation and in patients undergoing interleukin/LAK cell therapy may be beneficial.}, } @article {pmid2602612, year = {1989}, author = {Pascual, MA and Povar, J and Muñoz, JR and Cabeza, FJ and Portoles, A and Casado, JL and Loren, B and Ibarra, F}, title = {[Pericardial mesothelioma: apropos of a case].}, journal = {Revista espanola de cardiologia}, volume = {42}, number = {8}, pages = {559-561}, pmid = {2602612}, issn = {0300-8932}, mesh = {Heart Neoplasms/*diagnosis ; Humans ; Male ; Mesothelioma/*diagnosis ; Middle Aged ; Pericardium ; }, abstract = {We report a case of primary pericardial malignant mesothelioma in a 53-year old male with no asbestos previous exposure. The first clinical sign was a massive pericardial effusion causing hemodynamic disturbances. CT confirmed the initial ecochardiographic diagnosis. The patient underwent pericardiocentesis which improved his hemodynamic status as well as showed malignant cellularity in the liquid examination. Surgical treatment, including pericardiectomy and tumor resection, together with chemotherapy restored normal hemodynamics, the patient being now asymptomatic. We want to emphasize the rarity of this tumor and its insidious clinical presentation even leading to hemodynamic impairment, as well as the great value of echocardiography and CT in its diagnosis, although, in some cases, thoracotomy has been the only valid diagnostic procedure.}, } @article {pmid2531313, year = {1989}, author = {Schmolz, G}, title = {[The carcinogenic effect of asbestos].}, journal = {Das Offentliche Gesundheitswesen}, volume = {51}, number = {10}, pages = {614-620}, pmid = {2531313}, issn = {0029-8573}, mesh = {Air Pollutants/*adverse effects ; Asbestos/*adverse effects ; Germany, West ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Peritoneal Neoplasms/*etiology ; Pleural Neoplasms/*etiology ; Risk Factors ; }, abstract = {There is a causal correlation between the inhaled dose of asbestos at the working place, the occurrence of asbestosis, and a 5-fold increased mortality rate of lung cancer. Mesothelioma, which appears to be very rare among the general population, is a specific sign of exposure to asbestos fibres. Malignant tumours of the urinary bladder, the gastro-intestinal tract, the larynx and the oesophagus in workers may also be ascribed to the specific exposure in some cases. After a brief outline of the epidemiology of these diseases the carcinogenic effects of asbestos on the cellular and subcellular level are described. It can be shown from most recent literature that asbestos fibres can also trigger epigenetic and genotoxic effects. Numeric mutation of chromosomes, damage of the plasma membrane, and a modification of the immune system are most significant. In the presence of PAH, asbestos acts as a cocarcinogen. Asbestos fibres are positive in the cellular transformation test. Due to its initiating and promoting effects, asbestos proves to be a complete carcinogen. Obviously, asbestos fulfils the criteria of the modern theory of carcinogenesis as a multicausal and multistep process.}, } @article {pmid2813193, year = {1989}, author = {Brinkmann, OA and Müller, KM}, title = {What's new in intraperitoneal test on Kevlar (asbestos substitute)?.}, journal = {Pathology, research and practice}, volume = {185}, number = {3}, pages = {412-417}, doi = {10.1016/S0344-0338(89)80027-5}, pmid = {2813193}, issn = {0344-0338}, mesh = {Animals ; Granuloma/chemically induced/pathology ; Microscopy, Electron, Scanning ; Peritoneal Cavity/*pathology ; Peritoneal Diseases/chemically induced/pathology ; Polymers ; Rats ; Rats, Inbred Strains ; }, abstract = {The intraperitoneal test is a suitable experimental method for studying the different patterns of morphological reaction to foreign body substances of various kinds and concentrations as well as their transport within and elimination from the organism, Kevlar fibres are synthetic aromatic polyamid (aramid) fibres which, investigated by means of the intraperitoneal test in Wistar rats, show distinct pathogenetic reaction patterns: 1. In the early stage after application, the formation of multinucleated giant cells with phagocytosis of the amber-coloured Kevlar fibres, and an inflammatory reaction are foremost features. 2. The typical feature of the second stage is the development of granulomas with central necrosis indicating the cytotoxic nature of Kevlar fibres. 3. The third stage is dominated by the mesenchymal activation with capsular structures of collagenous fibres. Besides granulomatous foci, a slight submesothelial fibrosis is observed. 4. Fragments of Kevlar fibres are drained through lymphatic pathways and stored in lymph nodes where they lead to inflammatory reactions. 5. The reactive granulomatous changes in the greater omentum of rats are accompanied by proliferative mesothelial changes which, in one cases, even led to the development of a multilocular mesothelioma.}, } @article {pmid2585907, year = {1989}, author = {Shibata, M and Oki, Y and Iwata, M and Ogasawara, B and Watanabe, H and Noda, Y and Takagi, K and Imaizumi, M}, title = {[A case of malignant pleural mesothelioma with infectious bronchogenic cyst].}, journal = {Nihon Kyobu Shikkan Gakkai zasshi}, volume = {27}, number = {9}, pages = {1100-1105}, pmid = {2585907}, issn = {0301-1542}, mesh = {Bronchogenic Cyst/*complications ; Humans ; Male ; Mesothelioma/*complications/diagnosis ; Middle Aged ; Pleural Neoplasms/*complications/diagnosis ; }, abstract = {A 47-year-old man was admitted with a cough on January 4, 1986. A chest X-ray film showed a mass shadow in the left lower lung, which was revealed to be a bronchogenic cyst by CT scanning and ultrasonography. Thoracotomy was performed on March 3, 1986 because cytologic tests on the fluid in the cyst suggested malignancy. A cyst, two tumors on the diaphragm and pleural thickening were revealed. Microscopic examination showed a benign bronchogenic cyst and a mixed-type malignant mesothelioma. In spite of chemotherapy (ADR, Cis-DPP, 5-fluorouracil) and immunotherapy (OK-432, PSK), the pleural thickening progressed, as was demonstrated by CT scanning and ultrasonography. Although cardiac tamponade due to invasion by the malignant mesothelioma developed, this was improved by cardiocentesis. The patient died of pneumonia on March 28, 1987. We studied the concentration of mineral fibers in lung and tumor tissues of this case by Energy Dispersive X-ray Analyser because asbestos or non-asbestos inorganic fibers might cause malignant mesothelioma. This case of malignant pleural mesothelioma accompanied by a bronchogenic cyst is very rare.}, } @article {pmid2553393, year = {1989}, author = {Churg, A and Wiggs, B}, title = {The distribution of amosite asbestos fibers in the lungs of workers with mesothelioma or carcinoma.}, journal = {Experimental lung research}, volume = {15}, number = {5}, pages = {771-783}, doi = {10.3109/01902148909062860}, pmid = {2553393}, issn = {0190-2148}, mesh = {Aged ; Asbestos/*analysis ; Asbestos, Amosite ; Carcinoma/*analysis ; Humans ; Lung Neoplasms/*analysis ; Mesothelioma/*analysis ; Middle Aged ; Smoking ; Tissue Distribution ; }, abstract = {We have previously shown that there are differences in the sizes of fibers of amosite asbestos in different parts of the lung in workers with relatively high asbestos exposure and malignant pleural mesothelioma. To determine whether this distribution pattern is specific to cases of mesothelioma, we compared the fiber distribution in the lungs of 20 cases of mesothelioma and 10 cases of carcinoma of the lung. The two test groups were statistically identical in terms of age, and exposure period, and overall both groups had very similar mean fiber concentrations and mean fiber sizes. When individual sampling sites within the lung were considered, neither group showed preferential fiber concentration in any area. However, there were definite differences in the intrapulmonary fiber size distribution both within and between the two groups: Cases of mesothelioma showed accumulation of lung fibers in the peripheral upper lobe with shorter central upper lobe fibers. The lung cancer cases demonstrated a reverse pattern, with shorter fibers in the peripheral compared to central upper lobe, but accumulations of long fibers in the peripheral lower lobe. Fiber surfaces and masses showed similar differences among sample sites. We conclude that (1) there is no evidence for fiber concentration variations in different portions of the lung; (2) there is strong evidence for variations in fiber sizes in different portions of the lung, and these differences are most clearly related to fiber length, surface area, and mass; (3) contrary to data from experimental animals, there are no clear gravitational effects on fiber distribution in humans; and (4) there are reproducible differences in intrapulmonary fiber size distribution between mesothelioma and lung cancer cases. These differences may be a manifestation of individual handling of mineral particles because of structural variations in individual lungs.}, } @article {pmid2766251, year = {1989}, author = {Olofsson, K and Mark, J}, title = {Specificity of asbestos-induced chromosomal aberrations in short-term cultured human mesothelial cells.}, journal = {Cancer genetics and cytogenetics}, volume = {41}, number = {1}, pages = {33-39}, doi = {10.1016/0165-4608(89)90105-2}, pmid = {2766251}, issn = {0165-4608}, mesh = {Asbestos/*adverse effects ; Cells, Cultured ; *Chromosome Aberrations ; Chromosome Banding ; Humans ; Karyotyping ; Mesothelioma/*etiology/genetics ; Pleural Neoplasms/*etiology/genetics ; }, abstract = {Short-term cultured normal human mesothelial cells were exposed for 48 hours to three different asbestos compounds, crocidiolite, chrysotile, and amosite. In the concentration used (0.01 mg/ml) all three asbestiform minerals caused, within a few days, a significant increase of cells showing numerical and/or structural abnormalities. The abnormalities were analyzed in detail using banding techniques. The results were compared with the cytogenetic observations in 52 published cases of mesotheliomas. This comparison revealed only a few similarities as regards numerical deviations. The structural rearrangements in asbestos-exposed cultures, however, in many instances involved chromosome types and chromosome regions preferentially affected in mesotheliomas.}, } @article {pmid2751042, year = {1989}, author = {Andrion, A and Mazzucco, G and Bernardi, P and Mollo, F}, title = {Sarcomatous tumor of the chest wall with osteochondroid differentiation. Evidence of mesothelial origin.}, journal = {The American journal of surgical pathology}, volume = {13}, number = {8}, pages = {707-712}, doi = {10.1097/00000478-198908000-00010}, pmid = {2751042}, issn = {0147-5185}, mesh = {Asbestos/adverse effects ; Female ; Humans ; Immunohistochemistry ; Mesothelioma/analysis/etiology/*pathology ; Middle Aged ; Occupational Diseases/etiology/pathology ; Pleural Neoplasms/analysis/etiology/*pathology ; Sarcoma/analysis/etiology/*pathology ; }, abstract = {We describe a case of sarcomatous tumor of the chest wall with differentiation toward bone and cartilage that was observed in an asbestos-exposed worker. Although the mesothelial nature of the tumor was at first considered, it was not proven. Later, the tumor was shown to be a mesothelioma using a panel of pertinent antibodies that included a recently described anti-mesothelial cell marker. In addition, asbestos bodies were found in association with the sarcoma cells. Our findings indicate that whenever physicians encounter any type of primary sarcomatoid tumor involving serous membranes, the possibility of malignant mesothelioma should be regarded a priori.}, } @article {pmid2701739, year = {1989}, author = {Landa, L and Fianchini, A and Gesuelli, GC and Catalini, GB and Fonti, M}, title = {[Role of surgery in the treatment of pleural mesothelioma].}, journal = {Chirurgia italiana}, volume = {41}, number = {4-6}, pages = {192-206}, pmid = {2701739}, issn = {0009-4773}, mesh = {Aged ; Asbestos/adverse effects ; Biopsy ; Clinical Protocols ; Female ; Humans ; Male ; Mesothelioma/diagnostic imaging/etiology/pathology/*surgery ; Middle Aged ; Neoplasm Invasiveness ; Occupational Diseases/diagnostic imaging/etiology/pathology/*surgery ; Pleural Neoplasms/diagnostic imaging/etiology/pathology/*surgery ; Radiography ; }, abstract = {The authors present a review of the cases of pleural mesothelioma diagnosed and treated in the Institute of Special Surgical Pathology of the University of Ancona. They confirm the causative role of asbestos in the aetiology of this disease and indicate that the surgical approach is the best diagnostic means available via open biopsy and that the only curative procedure is pleuropneumonectomy. Such surgery, however, is confined to patients properly studied according to the scheme proposed by Butchart, namely stage I patients in excellent physical condition.}, } @article {pmid2669306, year = {1989}, author = {Tyagi, G and Munn, CS and Kiser, LC and Wetzner, SM and Tarabulcy, E}, title = {Malignant mesothelioma of tunica vaginalis testis.}, journal = {Urology}, volume = {34}, number = {2}, pages = {102-104}, doi = {10.1016/0090-4295(89)90174-x}, pmid = {2669306}, issn = {0090-4295}, mesh = {Aged ; Asbestos/adverse effects ; Environmental Exposure ; Humans ; Male ; Mesothelioma/*diagnosis/diagnostic imaging/etiology ; Scrotum/pathology ; Serous Membrane/pathology ; Testicular Neoplasms/*diagnosis/diagnostic imaging/etiology ; Tomography, X-Ray Computed ; Ultrasonography ; }, abstract = {Malignant mesothelioma of the tunica vaginalis is rare, but sometimes curable. It is similar to malignant mesothelioma of the peritoneum and of the pleura, and is likewise associated with asbestos exposure. We report a case, with correlative computed tomography, ultrasound, and gross pathology images that demonstrate tiny tumor implants studding the vaginalis testis. The literature is reviewed.}, } @article {pmid2666592, year = {1989}, author = {Ruffie, P and Feld, R and Minkin, S and Cormier, Y and Boutan-Laroze, A and Ginsberg, R and Ayoub, J and Shepherd, FA and Evans, WK and Figueredo, A}, title = {Diffuse malignant mesothelioma of the pleura in Ontario and Quebec: a retrospective study of 332 patients.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {7}, number = {8}, pages = {1157-1168}, doi = {10.1200/JCO.1989.7.8.1157}, pmid = {2666592}, issn = {0732-183X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos ; Environmental Exposure ; Female ; Humans ; Male ; Mesothelioma/diagnosis/*epidemiology/mortality/therapy ; Middle Aged ; Multicenter Studies as Topic ; Ontario ; Pleural Neoplasms/diagnosis/*epidemiology/mortality/therapy ; Prognosis ; Quebec ; Retrospective Studies ; }, abstract = {Three-hundred thirty-two cases of pleural diffuse malignant mesothelioma (DMM) seen at large centers in Ontario and Quebec from 1965 to 1984 were reviewed retrospectively. Previous asbestos exposure was found in 44% of patients. Diagnosis was most often made by exploratory thoracotomy; pleural biopsy or cytology were rarely contributory. The delay in diagnosis was often long (median time, 3.5 months) and thrombocytosis (platelets greater than or equal to 400,000/microL) was common (41% of cases). The median survival (MS) was only 9 months. Eleven clinical variables were analyzed for prognostic significance. The three most important prognostic factors using a univariate analysis were stage, weight loss, and histologic type. For 118 patients with complete data, multivariate analysis showed that the stage of disease, high platelet count, and asbestos exposure were the most important prognostic factors. There was no cure of DMM, and we did not find any drastic differences in survival among groups of patients subjected to the different therapeutic measures. Radical surgery and radiotherapy were ineffective and we confirmed the low response rate to chemotherapeutic agents. This large retrospective trial can serve as a baseline for future studies in this field. In particular, it provides the basis for appropriate stratification variables to be used in future therapeutic trials.}, } @article {pmid2550048, year = {1989}, author = {de Klerk, NH and Armstrong, BK and Musk, AW and Hobbs, MS}, title = {Cancer mortality in relation to measures of occupational exposure to crocidolite at Wittenoom Gorge in Western Australia.}, journal = {British journal of industrial medicine}, volume = {46}, number = {8}, pages = {529-536}, pmid = {2550048}, issn = {0007-1072}, mesh = {Asbestos/*adverse effects ; Asbestos, Crocidolite ; Cohort Studies ; Humans ; Lung Neoplasms/etiology/*mortality ; Mesothelioma/etiology/*mortality ; Mining ; Occupational Diseases/etiology/*mortality ; Pleural Neoplasms/etiology/*mortality ; Risk Factors ; Stomach Neoplasms/etiology/*mortality ; Time Factors ; Western Australia ; }, abstract = {The separate and combined effects of duration and intensity of exposure to crocidolite on mortality from lung cancer, malignant mesothelioma, and stomach cancer were examined in 6506 male former crocidolite miners and millers at Wittenoom Gorge, Western Australia. Each subject who had died from lung cancer (92), mesothelioma (31), or stomach cancer (17) was matched with up to 20 control subjects of the same age who were not known to have died before the index subject. Relations of dose and time of exposure to crocidolite to risk of death were modelled by conditional logistic regression. For lung cancer, the best fitting multiplicative model was one which estimated a relative risk (RR) of 1.12 (95% CI 1.04-1.20) per year of exposure and 1.01 (95% CI 1.00-1.01) per fibre/ml. This was statistically indistinguishable from an additive model showing an increase in RR of 0.01045 (95% CI 0.008-0.020) per f/ml year. For mesothelioma the best fitting model appeared to be one estimating a RR of 24.9 (95% CI 3.51-1.77) per log year since first exposed and a RR of 10.5 (95% CI 3.12-35.1) if exposed for longer than six months. This was not distinguishable statistically from a model that showed mortality increasing as the fourth power of time since first exposed less the fourth power of time since last exposed. The effect of intensity of exposure on the RR for mesothelioma was only slight. There was no consistent effect of any measure of exposure to crocidolite on death from stomach cancer.}, } @article {pmid2781528, year = {1989}, author = {Wojtukiewicz, MZ and Zacharski, LR and Memoli, VA and Kisiel, W and Kudryk, BJ and Rousseau, SM and Stump, DC}, title = {Absence of components of coagulation and fibrinolysis pathways in situ in mesothelioma.}, journal = {Thrombosis research}, volume = {55}, number = {2}, pages = {279-284}, doi = {10.1016/0049-3848(89)90445-3}, pmid = {2781528}, issn = {0049-3848}, support = {HL21465/HL/NHLBI NIH HHS/United States ; HL35058/HL/NHLBI NIH HHS/United States ; HL35246/HL/NHLBI NIH HHS/United States ; }, mesh = {Asbestos/adverse effects ; Blood Coagulation Factors/*analysis ; *Fibrinolysis ; Humans ; Immunohistochemistry ; Mesothelioma/*blood ; Models, Biological ; Pleural Neoplasms/*blood ; }, } @article {pmid2545323, year = {1989}, author = {Finkelstein, MM}, title = {Mortality rates among employees potentially exposed to chrysotile asbestos at two automotive parts factories.}, journal = {CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne}, volume = {141}, number = {2}, pages = {125-130}, pmid = {2545323}, issn = {0820-3946}, mesh = {Adult ; Asbestos/*adverse effects ; Asbestos, Serpentine ; Asbestosis/*mortality ; *Automobiles ; Cause of Death ; Cohort Studies ; Female ; Follow-Up Studies ; Humans ; *Industry ; Male ; Neoplasms/mortality ; Ontario ; Risk Factors ; Time Factors ; }, abstract = {A study of the mortality rates among 1657 employees at two Ontario automotive parts factories that manufactured friction materials containing chrysotile asbestos was initiated in response to the workers' concerns about the effects of asbestos on their health. A total of 1194 men and 258 women had had their first potential exposure at least 10 years before the end of the study period; 563 of the men and 138 of the women had had such an exposure at least 20 years before the end of the study period. A significantly increased rate of death from laryngeal cancer and an elevated rate of death from lung cancer were observed in a cohort analysis. One or two deaths might have been due to pleural mesothelioma. There was no increase in the rate of death from gastrointestinal cancer or from nonmalignant respiratory disease. Case-control analysis showed no association between the risk of laryngeal or lung cancer and the total duration of employment (a surrogate for the extent of ambient exposure to asbestos or other workplace toxic substances) or employment in departments where asbestos had been used. An association between risk of death and occupational exposure is uncertain.}, } @article {pmid2810965, year = {1989}, author = {Umeki, S and Kawai, S and Hino, J and Adachi, M and Yagi, S and Soejima, R}, title = {[Prognostic factors in cases of diffuse malignant pleural mesothelioma].}, journal = {Nihon Kyobu Shikkan Gakkai zasshi}, volume = {27}, number = {7}, pages = {768-776}, pmid = {2810965}, issn = {0301-1542}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Mesothelioma/*diagnosis/mortality ; Middle Aged ; Pleural Neoplasms/*diagnosis/mortality ; Prognosis ; Survival Rate ; }, abstract = {Among 56 cases of diffuse malignant pleural mesothelioma (including three cases from our institute and 53 reported in Japan from 1978 to 1987), we investigated several prognostic factors, such as age, sex, exposure to asbestos, smoking history, symptom duration, tuberculin skin test, localization of the lesion, pleural effusion, histologic type, metastasis, treatment and some laboratory data, concerning periods from the appearance of symptoms to death. In our series, exposure to asbestos, smoking history, localization of the lesion, pleural effusion and histologic type have no influence on the median survival from symptoms. However, the median survival from symptoms was significantly shorter in males, subjects more than 49 years of age, those having symptoms less than 6 months, those with a negative tuberculin skin test, or those with metastasis of the tumor compared with females, subjects less than 50 years of age, those having symptoms more than 6 months, those with a positive tuberculin skin test, or those without metastasis of the tumor, respectively. In subjects receiving surgery, anticancer chemotherapy, or no treatment, the fifty percent survival period was about 16, 9, or 6 months, respectively. There were, however, no significant relationships between the median survival from symptoms and the Brinkmann smoking index, or the median survival from symptoms and period of asbestos exposure.}, } @article {pmid2765424, year = {1989}, author = {Huncharek, M and Muscat, J and Capotorto, J}, title = {Pleural mesothelioma in a lift mechanic.}, journal = {British journal of industrial medicine}, volume = {46}, number = {7}, pages = {500-501}, pmid = {2765424}, issn = {0007-1072}, mesh = {Asbestos/*adverse effects ; Humans ; Male ; Mesothelioma/*chemically induced/pathology ; Middle Aged ; Occupational Diseases/*chemically induced/pathology ; Pleura/pathology ; Pleural Neoplasms/*chemically induced/pathology ; }, } @article {pmid2661172, year = {1989}, author = {Aisner, J}, title = {Therapeutic approach to malignant mesothelioma.}, journal = {Chest}, volume = {96}, number = {1 Suppl}, pages = {95S-97S}, doi = {10.1378/chest.96.1_supplement.95s}, pmid = {2661172}, issn = {0012-3692}, mesh = {Asbestos/*adverse effects ; Combined Modality Therapy ; Humans ; Mesothelioma/*therapy ; Pleural Neoplasms/*therapy ; }, } @article {pmid2577816, year = {1989}, author = {Vetere, C}, title = {[Health program for an effective primary prevention of carcinoma of the lung].}, journal = {Archivio Monaldi per le malattie del torace}, volume = {44}, number = {4-6}, pages = {937-950}, pmid = {2577816}, issn = {1120-0391}, mesh = {Air Pollution/adverse effects ; Asbestos/adverse effects ; Health Education ; Humans ; Italy ; Lung Neoplasms/etiology/*prevention & control ; Mesothelioma/etiology/prevention & control ; Preventive Medicine/legislation & jurisprudence/*organization & administration ; Program Development ; Smoking/adverse effects ; }, } @article {pmid2544379, year = {1989}, author = {Craighead, JE}, title = {The epidemiology and pathogenesis of malignant mesothelioma.}, journal = {Chest}, volume = {96}, number = {1 Suppl}, pages = {92S-93S}, doi = {10.1378/chest.96.1_supplement.92s}, pmid = {2544379}, issn = {0012-3692}, mesh = {Asbestos/*adverse effects ; Asbestos, Amphibole ; Humans ; *Mesothelioma/epidemiology/etiology ; *Pleural Neoplasms/epidemiology/etiology ; Silicon Dioxide/adverse effects ; }, } @article {pmid2659987, year = {1989}, author = {Mossman, BT and Gee, JB}, title = {Asbestos-related diseases.}, journal = {The New England journal of medicine}, volume = {320}, number = {26}, pages = {1721-1730}, doi = {10.1056/NEJM198906293202604}, pmid = {2659987}, issn = {0028-4793}, mesh = {Asbestos/*adverse effects ; Asbestosis ; Environmental Exposure ; Humans ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Pleural Diseases/etiology ; }, } @article {pmid2733039, year = {1989}, author = {Reddel, RR and Malan-Shibley, L and Gerwin, BI and Metcalf, RA and Harris, CC}, title = {Tumorigenicity of human mesothelial cell line transfected with EJ-ras oncogene.}, journal = {Journal of the National Cancer Institute}, volume = {81}, number = {12}, pages = {945-948}, doi = {10.1093/jnci/81.12.945}, pmid = {2733039}, issn = {0027-8874}, mesh = {Animals ; Cell Line, Transformed ; Cell Transformation, Neoplastic/*genetics ; Drug Resistance/genetics ; Gentamicins/pharmacology ; Humans ; Mesothelioma/*genetics/pathology ; Mice ; Mice, Nude ; Neoplasm Transplantation ; *Oncogenes ; Transfection ; }, abstract = {We performed this study to determine whether human mesothelial cells are capable of undergoing neoplastic change in vitro and to observe their interaction with the activated c-Ha-ras (HRAS1) oncogene EJ-ras, which has a role in the development of many malignant human tumors. Mesothelial cells are presumed to be the progenitor cells of malignant mesothelioma, a cancer strongly correlated with asbestos exposure. Previously, we established a non-tumorigenic cell line, MeT-5A, from normal human mesothelial cells after transfection with a plasmid containing the simian virus 40 (SV40) early-region genes. In the present study, we performed transfection of a plasmid containing the EJ-ras gene and the neomycin-resistance gene into these cells and selected a population resistant to G418, a neomycin analogue. Cells from this cell line formed rapidly growing sc tumors in NIH Swiss athymic nude mice, but untransfected with the vector DNA and selected for G418 resistance formed no tumors. The tumors formed by EJ-ras-transfected cells were established in vitro, and cells from these tumor cell lines exhibited a characteristic altered morphology. The cells had the same isoenzyme phenotype as the parent cells, and they expressed the mutant EJ-ras p21 protein. This first demonstration of malignant transformation of human mesothelial cells in vitro may permit molecular analysis of mesothelial carcinogenesis.}, } @article {pmid2804773, year = {1989}, author = {Kuo, HP and Shieh, WB and Chiang, YC and Tasi, YH and Lan, RS and Lee, CH}, title = {Pleural mesothelioma--analysis of 12 cases in Chang-Gung Memorial Hospital.}, journal = {Changgeng yi xue za zhi}, volume = {12}, number = {2}, pages = {89-101}, pmid = {2804773}, mesh = {Adenocarcinoma/pathology ; Adolescent ; Adult ; Aged ; Diagnosis, Differential ; Female ; Humans ; Male ; Mesothelioma/*diagnosis/pathology ; Middle Aged ; Pleural Neoplasms/*diagnosis/pathology ; Prognosis ; }, abstract = {Twelve cases of pathologically proved pleural mesothelioma collected from 1983 to 1987 were analyzed retrospectively. There were 9 males, and 3 females, aged 14-76 year-old (mean 54 year-old). Eight cases were malignant mesothelioma. Four cases were benign mesothelioma. The male to female ratio in malignant tumor was 1 to 7; in benign tumor it was 1 to 1. The mean age in malignant mesothelioma was 45 year-old, and in benign mesothelioma it was 58. Of the 8 cases with malignant mesothelioma, there were 2 cases (25%) of fibrous type, 1 case (12.5%) of epithelial type, and 5 cases (62.5%) of mixed type. Asbestos exposure history was not evident in our series. Definitive diagnosis was obtained in 10 cases by thoracotomy (83%). Two cases of malignant mesothelioma were verified by pleural biopsy. The diagnostic yield is 40% for pleural biopsy, and 100% for thoracotomy. Bronchoscopic examination, percutaneous biopsy, and pleural effusion analysis were useless in making a definitive diagnosis and distinguishing from metastatic adenocarcinoma in our opinions.}, } @article {pmid2749671, year = {1989}, author = {Borgersen, A and Ostensen, H and Hanoa, R}, title = {[Occupational pneumoconiosis and x-ray check-ups performed by the National Board of Occupational Protection].}, journal = {Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke}, volume = {109}, number = {17-18}, pages = {1887-1890}, pmid = {2749671}, issn = {0029-2001}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Norway ; Pneumoconiosis/diagnostic imaging/*etiology/prevention & control ; Radiography ; }, abstract = {In Norway the Directorate of Labour Inspection's pneumoconiosis panel consists of two radiologists. Pneumoconioses are notifiable diseases, and doctors are required by law to notify suspected and confirmed cases to the Directorate of Labour Inspection. Chest films are sent to the Directorate. The pneumoconiosis panel reads and classifies the cases according to ILO-standards. During a 9 months' period, 177 chest films were examined, 162 of which were from persons exposed mainly to asbestos. In this group of 162, 96 persons had parietal pleural plaques only, and 21 or 17% had pleuropulmonary asbestosis with visceral pleural thickening from which fibrous streaks radiated into the lung. Ten persons had pulmonary asbestosis alone or combined with pleural plaques. This group included one mesothelioma. The notification form used by the doctors demands adequate information on occupational history and exposures. More specific information would facilitate the work of the panel.}, } @article {pmid2567424, year = {1989}, author = {Weinberg, ED}, title = {Iron, asbestos, and carcinogenicity.}, journal = {Lancet (London, England)}, volume = {1}, number = {8651}, pages = {1399-1400}, doi = {10.1016/s0140-6736(89)92857-2}, pmid = {2567424}, issn = {0140-6736}, mesh = {Asbestos/*adverse effects/classification ; Humans ; Iron/*adverse effects ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; }, } @article {pmid2749656, year = {1989}, author = {Skaug, V and Mowé, G and Skogstad, A}, title = {[Health damage caused by asbestos and other mineral fibers].}, journal = {Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke}, volume = {109}, number = {16}, pages = {1786-1789}, pmid = {2749656}, issn = {0029-2001}, mesh = {Asbestos/*adverse effects ; Humans ; Lung Diseases/*etiology ; Minerals/*adverse effects ; Norway ; Occupational Diseases/*etiology ; Risk Factors ; }, abstract = {Occupational exposure to asbestos is associated with malignant tumors in the lung and malignant mesothelioma in the pleura and peritoneum. Tumors at other sites have also been reported. The benign asbestos-related disorders are asbestosis and pleural fibrosis, effusion and plaques. Chronic bronchitis may be associated with previous asbestos exposure. Fiber dimensions and durability are main factors for carcinogenicity. For practical reasons, long and thin fibers like asbestos should be considered carcinogenic. The diagnosis of asbestos-related disease is based upon information on occupational exposure. Analysis of lung fiber burden supports information given by the occupational history and gives valuable information on dose-response and dose-effect relationships. Building materials with good maintainance of the surfaces do not release asbestos fibers, whereas materials subject to mechanical stress should be replaced by nonasbestos-containing materials to avoid the stipulated very low increase in cancer risk.}, } @article {pmid2767845, year = {1989}, author = {Zwi, AB and Reid, G and Landau, SP and Kielkowski, D and Sitas, P and Becklake, MR}, title = {Mesothelioma in South Africa, 1976-84: incidence and case characteristics.}, journal = {International journal of epidemiology}, volume = {18}, number = {2}, pages = {320-329}, doi = {10.1093/ije/18.2.320}, pmid = {2767845}, issn = {0300-5771}, mesh = {Aged ; Asbestos ; Female ; Humans ; Male ; Mesothelioma/analysis/*epidemiology/ethnology ; Middle Aged ; Mining ; Occupational Diseases/*epidemiology/ethnology ; South Africa ; }, abstract = {Malignant mesothelioma is a rare tumour known to be associated with prior exposure to asbestos. Previous studies have described the occupational and clinical features of cases of mesothelioma in the Republic of South Africa (RSA) but none has set out to determine incidence of this disease. To estimate incidence, a case register was compiled for 1976-84 by contacting all medical practitioners and institutions likely to have seen cases of mesothelioma in this period; demographic, diagnostic and exposure details were sought. Cases were accepted if they provided evidence of histological diagnosis of mesothelioma. Fifty-two per cent of 1347 cases identified were in whites, 31% in blacks, 16% in coloureds and 1% in Asians. Seventy-three per cent of cases occurred in males. The majority of whites were aged 51-70 years, while the majority in other race groups were aged 41-60 years. The ratio of only pleural to only peritoneal mesothelioma was 11:1, although there were marked differences by race. Eighty-five per cent of males with exposure information available had prior exposure to asbestos, mostly occupational. A similar proportion of women had contact with asbestos but mostly through other types of exposure. Standardized incidence rates per million population aged 15 years and over were calculated for sex-race subgroups and were highest in white males (32.9 per million per year, 95% Cl 22.7-46.4), coloured males (24.8 per million per year, 95% Cl 16.2-36.9) and coloured females (13.9 per million per year, 95% Cl 7.7-23.5). These incidence rates are amongst the highest ever reported for a national population. Age-specific standardized incidence rates were highest in white males (over 100 per million per year in men over 55 years). Reasons for the differing rates by population group are likely to include differential access to health services. More rigorous control of asbestos exposure in the RSA is recommended.}, } @article {pmid2763260, year = {1989}, author = {Hulks, G and Thomas, JS and Waclawski, E}, title = {Malignant pleural mesothelioma in western Glasgow 1980-6.}, journal = {Thorax}, volume = {44}, number = {6}, pages = {496-500}, pmid = {2763260}, issn = {0040-6376}, mesh = {Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Female ; Humans ; Male ; Mesothelioma/etiology/*pathology ; Middle Aged ; Pleural Neoplasms/etiology/*pathology ; Prognosis ; Scotland ; }, abstract = {This study reviews all histologically proved cases of malignant pleural mesothelioma seen in the western district of Glasgow during 1980-6. Sixty eight cases were identified (three female) with an age range at presentation of 48-85 (mean 68.9) years. Asbestos exposure was identified in 54 (80%) of the patients, most of whom had been shipyard workers. Pain and dyspnoea were the most common presenting symptoms. Pleural effusion was found in 57 (84%) of the patients, in a ratio of 2.6 right:left. The median survival was only 30 weeks from the time of presentation. Prognosis was significantly better for those presenting with dyspnoea than for those with pain (median survival 44 v 22 weeks). Postmortem examination was performed in 40 cases and metastatic disease found in more than three quarters. There was no significant difference between the incidence of the various tumour cell types or any relation between cell type and survival or the incidence of metastatic disease. A substantial increase in cases of malignant pleural mesothelioma has been found in an area of already high incidence. The use of rigorous histological criteria to determine histological cell type has shown that this previously valued variable is of no discriminatory value with regard to disease activity or survival.}, } @article {pmid2656113, year = {1989}, author = {Dunn, MM}, title = {Asbestos and the lung.}, journal = {Chest}, volume = {95}, number = {6}, pages = {1304-1308}, doi = {10.1378/chest.95.6.1304}, pmid = {2656113}, issn = {0012-3692}, mesh = {Aged ; Asbestos/*adverse effects ; Asbestosis/*etiology/physiopathology ; Carcinoma, Bronchogenic/etiology ; Humans ; Lung Neoplasms/etiology ; Male ; Mesothelioma/etiology ; Pleural Diseases/etiology ; Pleural Neoplasms/etiology ; Prognosis ; Smoking/adverse effects ; }, } @article {pmid2533562, year = {1989}, author = {Neri, S and Iaia, TE and Battista, G and Roselli, MG}, title = {[Sentinel events in occupational medicine: the example of Local Health Unit No. 1 of the Tuscany region].}, journal = {Epidemiologia e prevenzione}, volume = {11}, number = {39}, pages = {29-34}, pmid = {2533562}, issn = {1120-9763}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Cause of Death ; Death Certificates ; Female ; *Health Status Indicators ; Humans ; Italy ; Male ; Middle Aged ; Occupational Diseases/*mortality ; }, abstract = {In order to apply the "sentinel health event" methodology we reviewed the certificates of 4541 deaths occurred in the period 1/01/83-31/12/88 in the USL 1 (Lunigiana) in the Tuscany Region. The histories of 6 work accidents, 6 cases of pleural mesothelioma, and 2 cases of sinunasal cancers have been collected by means of personal interviews and investigation at various workplaces. It should be noted that a case of sinunasal cancer was discovered in a farmer who used lead arsenate as an insecticidal. Furthermore the wife of a shipyard worker died of pleural mesothelioma. The death of a shipyard worker caused by pleural mesothelioma, provoked the critical review of the other workers of the same company who were also exposed to asbestos. Moreover, 73 deaths were recorded as due to silicosis; among them, 29 occurred in quartzite quarrymen. In addition, among 153 total cases of lung cancer, 9 were found to be associated with silicosis.}, } @article {pmid2716574, year = {1989}, author = {Orr, KB}, title = {The rising epidemic of malignant mesothelioma.}, journal = {The Medical journal of Australia}, volume = {150}, number = {10}, pages = {607}, pmid = {2716574}, issn = {0025-729X}, mesh = {Asbestos/*adverse effects ; *Disease Outbreaks ; Humans ; Lung Neoplasms/*epidemiology ; Mesothelioma/*epidemiology ; Pleural Neoplasms/*epidemiology ; }, } @article {pmid2751937, year = {1989}, author = {Huncharek, M and Capotorto, JV and Muscat, J}, title = {Domestic asbestos exposure, lung fibre burden, and pleural mesothelioma in a housewife.}, journal = {British journal of industrial medicine}, volume = {46}, number = {5}, pages = {354-355}, pmid = {2751937}, issn = {0007-1072}, mesh = {Aged ; Asbestos/*adverse effects ; Body Burden ; Clothing ; Environmental Exposure ; Female ; Humans ; Lung/*pathology ; Mesothelioma/*etiology/pathology ; Pleural Neoplasms/*etiology/pathology ; }, } @article {pmid2727359, year = {1989}, author = {Lynch, DA and Gamsu, G and Aberle, DR}, title = {Conventional and high resolution computed tomography in the diagnosis of asbestos-related diseases.}, journal = {Radiographics : a review publication of the Radiological Society of North America, Inc}, volume = {9}, number = {3}, pages = {523-551}, doi = {10.1148/radiographics.9.3.2727359}, pmid = {2727359}, issn = {0271-5333}, mesh = {Asbestosis/*diagnostic imaging ; Carcinoma, Bronchogenic/*diagnostic imaging ; Humans ; Lung Neoplasms/*diagnostic imaging ; Mesothelioma/*diagnostic imaging ; Pleural Diseases/*diagnostic imaging ; *Tomography, X-Ray Computed/methods ; }, abstract = {High resolution CT (HRCT) can image the fine structures of the lung parenchyma and the pleura. Analysis of supine and prone HRCT scans in 300 patients with asbestos exposure shows that asbestosis is characterized the following findings; (1) parenchymal bands, (2) increased interlobular septa, (3) increased intralobular core structures, (4) subpleural lines, and (5) dependent opacity. Pleural disease is well displayed on HRCT scans. Correlated studies with whole lung sections confirm the HRCT findings. Masses in asbestosis may be benign or malignant, and CT helps in their differentiation. HRCT correlates well with radiographic and clinical criteria for asbestosis and is more sensitive than either in detecting abnormalities.}, } @article {pmid2667990, year = {1989}, author = {Barrett, JC and Lamb, PW and Wiseman, RW}, title = {Multiple mechanisms for the carcinogenic effects of asbestos and other mineral fibers.}, journal = {Environmental health perspectives}, volume = {81}, number = {}, pages = {81-89}, pmid = {2667990}, issn = {0091-6765}, mesh = {Animals ; Asbestos/adverse effects/*toxicity ; *Carcinogens ; Carcinoma, Bronchogenic/etiology ; Cell Transformation, Neoplastic/etiology/genetics ; Cocarcinogenesis ; Humans ; Lung Neoplasms/etiology/genetics ; Mesothelioma/etiology/genetics ; Particle Size ; }, abstract = {Asbestos and other mineral fibers are carcinogenic to humans and animals but differ from many carcinogens in that they do not induce gene mutations. An understanding of these interesting human carcinogens, therefore, is an important problem in cancer research. Asbestos and other fibers induce predominantly two types of cancers: mesotheliomas and bronchogenic carcinomas. Fiber size is an important factor in the carcinogenic activity of these substances as has been shown for mesothelioma induction. For bronchogenic carcinomas, but not for mesotheliomas, a synergistic effect of asbestos exposure and cigarette smoke has been observed in humans. The mechanisms by which fibers alone versus fibers in concert with other carcinogens induce cancers are probably distinct. In addition to fiber dimensions, fiber durability and surface properties of fibers are important properties affecting carcinogenicity. Evidence exists that asbestos is a complete carcinogen, an initiator and a promoter. Multiple mechanisms must be operative to explain the diverse effects of mineral fibers. Although asbestos is inactive as a gene mutagen, there is now clear evidence that it induces chromosomal mutations (aneuploidy and aberrations) in a wide variety of mammalian cells including mesothelial cells. Asbestos also induces transformation of cells in culture including mesothelial cells and fibroblasts. A mechanism for cell transformation, which is dependent on fiber dimension, has been proposed. The fibers are phagocytized by the cells and accumulate in the perinuclear region of the cells. When the cell undergoes mitosis, the physical presence of the fibers interferes with chromosome segregation and results in anaphase abnormalities. The transformed cells show aneuploidy and other chromosome abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid2660312, year = {1989}, author = {Delclos, GL and Buffler, PA and Greenberg, SD and Key, MM and Perrotta, DM and Alexander, C and Wilson, RK}, title = {Asbestos-associated disease: a review.}, journal = {Texas medicine}, volume = {85}, number = {5}, pages = {50-59}, pmid = {2660312}, issn = {0040-4470}, mesh = {Asbestosis/*diagnosis ; Humans ; Lung Diseases, Obstructive/diagnosis ; Lung Neoplasms/diagnosis ; Mesothelioma/diagnosis ; Pleura/pathology ; Pleural Neoplasms/diagnosis ; }, abstract = {Asbestos and its potential for adversely affecting health remain a source of concern to several sectors of society. Since it rarely occurs in the absence of occupational exposure to asbestos, and because it is potentially preventable, asbestosis was recently defined as a reportable occupational disease in Texas. An overview of the cardinal characteristics of the asbestos minerals and their associated health effects is presented. The role of the primary physician in diagnosis and counseling of individuals with asbestos-associated diseases is addressed.}, } @article {pmid2556736, year = {1989}, author = {Stein, RC and Kitajewska, JY and Kirkham, JB and Tait, N and Sinha, G and Rudd, RM}, title = {Pleural mesothelioma resulting from exposure to amosite asbestos in a building.}, journal = {Respiratory medicine}, volume = {83}, number = {3}, pages = {237-239}, doi = {10.1016/s0954-6111(89)80038-1}, pmid = {2556736}, issn = {0954-6111}, mesh = {Asbestos/*adverse effects/isolation & purification ; Asbestos, Amosite ; Electron Probe Microanalysis ; *Environmental Exposure ; Female ; Humans ; Microscopy, Electron ; Middle Aged ; Pleura/analysis/ultrastructure ; Pleural Neoplasms/analysis/*etiology/ultrastructure ; }, } @article {pmid2541616, year = {1989}, author = {Ke, Y and Reddel, RR and Gerwin, BI and Reddel, HK and Somers, AN and McMenamin, MG and LaVeck, MA and Stahel, RA and Lechner, JF and Harris, CC}, title = {Establishment of a human in vitro mesothelial cell model system for investigating mechanisms of asbestos-induced mesothelioma.}, journal = {The American journal of pathology}, volume = {134}, number = {5}, pages = {979-991}, pmid = {2541616}, issn = {0002-9440}, mesh = {Animals ; Antigens, Polyomavirus Transforming/analysis ; Asbestos/*adverse effects/pharmacology ; Asbestos, Amosite ; Carcinogenicity Tests ; Cell Survival ; Cell Transformation, Neoplastic ; Cell Transformation, Viral ; Cells, Cultured ; Glycoproteins/genetics ; Growth Substances/pharmacology ; Humans ; Karyotyping ; Mesothelioma/etiology/genetics/*pathology ; Mice ; Mice, Nude ; Plasmids ; Plasminogen Activators/antagonists & inhibitors ; Plasminogen Inactivators ; Pleural Neoplasms/etiology/genetics/*pathology ; RNA, Messenger/analysis ; Simian virus 40/immunology/physiology ; Transfection ; }, abstract = {Normal human mesothelial (NHM) cells were transfected with a plasmid containing SV40 early region DNA. Individual colonies of transformed cells from several donors were subcultured for periods of 5 to 6 months and 60 to 70 population doublings (PDs) before senescence, in contrast to a culture lifespan of approximately 1 month and 15 PDs for NHM cells. One such culture, designated MeT-5A, escaped senescence and has been passaged continuously for more than 2 years. These cells had a single integrated copy of SV40 early region DNA in their genome, expressed SV40 large T antigen, and exhibited features of mesothelial cells including sensitivity to the cytotoxic effects of asbestos fibers. One year after injection subcutaneously or intraperitoneally in athymic nude mice, these cells remain nontumorigenic, and therefore are a potential model system for in vitro fiber carcinogenesis studies.}, } @article {pmid2497107, year = {1989}, author = {Lechner, JF and LaVeck, MA and Gerwin, BI and Matis, EA}, title = {Differential responses to growth factors by normal human mesothelial cultures from individual donors.}, journal = {Journal of cellular physiology}, volume = {139}, number = {2}, pages = {295-300}, doi = {10.1002/jcp.1041390211}, pmid = {2497107}, issn = {0021-9541}, mesh = {Adult ; Cell Division/drug effects ; DNA/biosynthesis ; Epidermal Growth Factor/pharmacology ; *Epithelial Cells ; Epithelium/drug effects ; Growth Substances/*pharmacology ; Humans ; Interferon-gamma/pharmacology ; Interleukin-2/pharmacology ; }, abstract = {A significant interindividual variation in the growth rates is found in normal cultured human mesothelial (NHM) cells derived from different donors. This variation is observed when the mesothelial cells are incubated in medium containing serum and when the potencies of several separate growth factors are measured by using defined media. Depending on the donor, gamma-interferon and interleukin-2 can be toxic, have no effect, or stimulate the growth rate of NHM cells. Cultured NHM cells can be induced to multiply by growth factors that are released by activated macrophages. Thus, interindividual variation in NHM cell growth control could play a role in the pathogenesis of mesothelioma for a person exposed to asbestos.}, } @article {pmid2564999, year = {1989}, author = {Li, FP and Dreyfus, MG and Antman, KH}, title = {Asbestos-contaminated nappies and familial mesothelioma.}, journal = {Lancet (London, England)}, volume = {1}, number = {8643}, pages = {909-910}, doi = {10.1016/s0140-6736(89)92916-4}, pmid = {2564999}, issn = {0140-6736}, mesh = {Adult ; Asbestos/*adverse effects ; Environmental Exposure ; Family Health ; Humans ; *Infant Care ; Male ; Mesothelioma/*etiology ; Middle Aged ; Pleural Neoplasms/*etiology ; Time Factors ; }, } @article {pmid2924262, year = {1989}, author = {McDonald, JC and Armstrong, B and Case, B and Doell, D and McCaughey, WT and McDonald, AD and Sébastien, P}, title = {Mesothelioma and asbestos fiber type. Evidence from lung tissue analyses.}, journal = {Cancer}, volume = {63}, number = {8}, pages = {1544-1547}, doi = {10.1002/1097-0142(19890415)63:8<1544::aid-cncr2820630815>3.0.co;2-g}, pmid = {2924262}, issn = {0008-543X}, mesh = {Asbestos/adverse effects/*analysis ; Canada ; Female ; Humans ; Lung Neoplasms/epidemiology/*etiology/pathology ; Male ; Mesothelioma/epidemiology/*etiology/pathology ; Sex Factors ; }, abstract = {Lung tissue samples from 78 cases from autopsy of mesothelioma in Canada, 1980 through 1984, and from matched referents were examined by optical and analytical transmission electron microscopic study. Concentrations of amosite, crocidolite, and tremolite fibers, and of typical asbestos bodies discriminated sharply between cases and referents. The distributions of chrysotile and anthophyllite/talc fibers and of all other natural and man-made inorganic fibers (greater than or equal to 8 microns) in the two series were quite similar. Relative risk was related to the concentration of long (greater than or equal to 8 microns) amphibole fibers with no additional information provided by shorter fibers. The proportion of long fibers was much higher for amphiboles than chrysotile and, except for chrysotile, systematically higher in cases than referents. Amphibole asbestos fibers could explain most mesothelioma cases in Canada and other inorganic fibers, including chrysotile, very few. Fibrous tremolite, contaminant of many industrial minerals including chrysotile, probably explained most cases in the Quebec mining region and perhaps 20% elsewhere.}, } @article {pmid2725943, year = {1989}, author = {Piffer, S and Zeni, G and Aldovini, D and Polla, E and Peterlongo, P}, title = {[Diagnosis and prognosis of malignant mesothelioma. A description of 8 clinical cases].}, journal = {Minerva medica}, volume = {80}, number = {4}, pages = {405-410}, pmid = {2725943}, issn = {0026-4806}, mesh = {Adult ; Female ; Humans ; Immunohistochemistry ; Italy ; Male ; Mesothelioma/*diagnosis/mortality/pathology ; Middle Aged ; Peritoneal Neoplasms/*diagnosis/mortality/pathology ; Peritoneum/pathology ; Pleura/pathology ; Pleural Neoplasms/*diagnosis/mortality/pathology ; Prognosis ; Retrospective Studies ; }, abstract = {A retrospective study of patients at the Trento S. Chiara Hospital in the period 1982-86 showed up 8 cases of malignant mesothelioma (7 pleural and 1 peritoneal). The histology was re-examined for each case and clinical records was also looked at so as to identify onset symptomatology, diagnostic procedures and treatment. A standard questionnaire given to patients or close relations revealed previous exposure to asbestos in 2 of 3 males and in none of the 5 females. There was also a significant delay in formulation of correct diagnosis, attributable on the hand to the nonspecificity of the symptomatology of onset and on the other to the inadequacy of currently available clinical and radiological procedures. Only histology with the aid of immunocytochemical procedures was able to pinpoint correct diagnosis, in life. The ineffectiveness of conventional therapies and the poor overall prognosis for these patients is confirmed.}, } @article {pmid2650654, year = {1989}, author = {Lin-Chu, M and Lee, YJ and Ho, MY}, title = {Malignant mesothelioma in infancy.}, journal = {Archives of pathology & laboratory medicine}, volume = {113}, number = {4}, pages = {409-411}, pmid = {2650654}, issn = {0003-9985}, mesh = {Adenocarcinoma/diagnosis ; Child, Preschool ; Diagnosis, Differential ; Female ; Humans ; Infant ; Male ; Mesothelioma/diagnosis/*pathology ; Pleural Neoplasms/diagnosis/*pathology ; }, abstract = {Malignant mesothelioma in infancy has rarely been reported in the literature. A 19-month-old female infant with massive malignant epithelial mesothelioma of the pleura underwent postmortem examination. Histochemical study confirmed the diagnosis by revealing acid mucosubstance in the tumor, which was removed by hyaluronidase. The tumor cell had clear cytoplasm that was positive for periodic acid-Schiff staining, which could be totally abolished by diastase. This correlated well with the electron microscopic finding that there had been massive accumulation of glycogen in the cytoplasm. There was no information about environmental exposure to asbestos.}, } @article {pmid2549614, year = {1989}, author = {Ribak, J and Seidman, H and Selikoff, IJ}, title = {Amosite mesothelioma in a cohort of asbestos workers.}, journal = {Scandinavian journal of work, environment & health}, volume = {15}, number = {2}, pages = {106-110}, doi = {10.5271/sjweh.1877}, pmid = {2549614}, issn = {0355-3140}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Asbestos, Amosite ; Humans ; Male ; Mesothelioma/*chemically induced/mortality ; Middle Aged ; New Jersey ; Occupational Diseases/*chemically induced/mortality ; Peritoneal Neoplasms/*chemically induced/mortality ; Pleural Neoplasms/*chemically induced/mortality ; }, abstract = {A cohort of 820 asbestos workers with a short duration of exposure to amosite between 1941 and 1945 was followed. These men were alive five years after starting work and were observed until 1988. Seventeen cases of malignant mesothelioma (eight pleural, nine peritoneal) were found. The mean age at the onset of exposure was 33 years for men with pleural mesothelioma and 30 years for those with peritoneal mesothelioma. Chest pain was the main symptom in pleural mesothelioma and abdominal pain in peritoneal mesothelioma. Open lung biopsy was the most useful diagnostic approach for pleural mesothelioma, whereas for peritoneal mesothelioma it was exploratory laparotomy. Pleural patients died of pulmonary insufficiency, and peritoneal patients of wasting and inanition. In both groups the death certificate diagnosis was less accurate than the clinical diagnosis at death. The mean survival was 12.5 months from first symptom to death for the pleural group and 5.4 months for the peritoneal group.}, } @article {pmid2467835, year = {1989}, author = {Branchaud, RM and MacDonald, JL and Kane, AB}, title = {Induction of angiogenesis by intraperitoneal injection of asbestos fibers.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {3}, number = {6}, pages = {1747-1752}, doi = {10.1096/fasebj.3.6.2467835}, pmid = {2467835}, issn = {0892-6638}, support = {K04 ES 00127/ES/NIEHS NIH HHS/United States ; R01 ES 03721/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; *Asbestos ; Asbestos, Crocidolite ; Asbestos, Serpentine ; DNA/biosynthesis ; Endothelium, Vascular/metabolism ; Fibroblasts/pathology ; Macrophages/pathology ; Mesothelioma/*etiology/pathology ; Mice ; Mice, Inbred C57BL ; Neovascularization, Pathologic/*pathology ; Peritoneum/*blood supply/pathology ; }, abstract = {Tumors and activated macrophages release angiogenic factors that stimulate migration and proliferation of capillaries. We studied the development of angiogenesis before the appearance of mesotheliomas in C57B1/6 mice. Weekly i.p. injections of crocidolite asbestos fibers produced mesotheliomas after 30-50 wk. The initial histologic response to asbestos fibers was a nodular lesion on the peritoneal lining composed of clusters of fibers, activated macrophages, and proliferating mesenchymal cells. The earliest visible evidence of angiogenesis was seen surrounding 7% of these lesions 14 days after a single injection of 200 micrograms of crocidolite asbestos fibers. After six weekly injections, 30% of the lesions containing asbestos fibers were surrounded by a capillary network radiating toward the center of the lesion. Other mineral fibers, including chrysotile asbestos and fiberglass, also induced angiogenesis after six weekly injections. In contrast, only 8% of the lesions containing short asbestos fibers (90.6% less than or equal to 2.0 microns) and 9% of the lesions containing silica particles showed evidence of angiogenesis. We conclude that tumorigenic mineral fibers induce angiogenesis in the peritoneal lining, whereas nontumorigenic mineral particles or short asbestos fibers are less effective. Ingrowth of new blood vessels around clusters of asbestos fibers may facilitate the later emergence of mesotheliomas at these sites.}, } @article {pmid2656445, year = {1989}, author = {Reichel, G}, title = {[Asbestos-induced bronchopulmonary diseases].}, journal = {Fortschritte der Medizin}, volume = {107}, number = {9}, pages = {205-209}, pmid = {2656445}, issn = {0015-8178}, mesh = {Asbestos/*adverse effects ; Asbestosis/*etiology ; Humans ; Lung Diseases/*etiology ; Risk Factors ; }, abstract = {Asbestos is a collective term for fibrous crystalline silicate minerals, which can be used to produce technically useful fibers. The various types of asbestos, such as chrysotile, crocidolite and amosite, may induce not only fibrotic changes in the pleura and lungs, but also carcinomas and mesotheliomas. The increasing industrial use of asbestos has led to a marked increase in bronchopulmonary diseases, which can be shown to be caused by occupational exposure to fine asbestos dust. In this overview, the pathological anatomy, differential diagnosis and occupational-medical assessment of the various conditions induced by asbestos are discussed.}, } @article {pmid2716620, year = {1989}, author = {Musk, AW and Dolin, PJ and Armstrong, BK and Ford, JM and de Klerk, NH and Hobbs, MS}, title = {The incidence of malignant mesothelioma in Australia, 1947-1980.}, journal = {The Medical journal of Australia}, volume = {150}, number = {5}, pages = {242-3, 246}, doi = {10.5694/j.1326-5377.1989.tb136455.x}, pmid = {2716620}, issn = {0025-729X}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Australia ; Female ; Humans ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Peritoneal Neoplasms/*epidemiology ; Pleural Neoplasms/*epidemiology ; }, abstract = {Details of patients with malignant mesothelioma that was diagnosed in Australia before 1981 were obtained by searching all possible sources throughout Australia as far into the past as possible and up to and including 1980. The earliest patient with mesothelioma who was identified was diagnosed in Victoria in 1947. By 1980, 535 (81%) men and 123 (19%) women had been diagnosed with the disease; only 14 persons were aged less than 35 years at the time of diagnosis (the youngest person was 15 years of age). The incidence rate in subjects who were 35 years or older at diagnosis was less than 1.0 cases per million person-years until 1964-1968, and then it rose progressively to 15.5 cases per million person-years in 1979-1980. The highest rate (69.7 cases per million person-years) was observed in 65- to 74-year-old men in 1979-1980. The incidence rate in Western Australia was greater than were the rates in other states of Australia after the mid 1960s. Pleural mesotheliomas accounted for 88% of cases in which the site of the tumour was known; peritoneal mesotheliomas accounted for 10% of such cases and "other" sites for 2% of such cases. In 6% of cases the site was not specified. The exposure to asbestos was stated as "definite" in 59% of the cases with a recorded history of exposure: 8% of all the cases in the study had been exposed to crocidolite (blue asbestos) from Wittenoom Gorge in Western Australia. The age at diagnosis of patients with known exposure to asbestos was similar to that in those without known exposure. The increases in the incidence of malignant mesothelioma in Australia follow the published trends in the production and use of the amphibole varieties of asbestos in this country after a lag period of between 20 and 30 years.}, } @article {pmid2716617, year = {1989}, author = {Ferguson, D}, title = {Malignant mesothelioma--the rising epidemic.}, journal = {The Medical journal of Australia}, volume = {150}, number = {5}, pages = {233-235}, doi = {10.5694/j.1326-5377.1989.tb136452.x}, pmid = {2716617}, issn = {0025-729X}, mesh = {Adult ; Asbestos/*adverse effects ; Australia ; *Disease Outbreaks ; *Environmental Exposure ; Female ; Humans ; Male ; Mesothelioma/*epidemiology/etiology ; Occupational Diseases/epidemiology ; Pleural Neoplasms/epidemiology/etiology ; }, } @article {pmid2920599, year = {1989}, author = {Lie, JT}, title = {Sudden death as the initial manifestation of diffuse pleural mesothelioma.}, journal = {Chest}, volume = {95}, number = {3}, pages = {682-684}, doi = {10.1378/chest.95.3.682}, pmid = {2920599}, issn = {0012-3692}, mesh = {Adult ; Death, Sudden/*etiology ; Humans ; Male ; Mesothelioma/*diagnosis/diagnostic imaging/pathology ; Pleural Neoplasms/*diagnosis/diagnostic imaging/pathology ; Prognosis ; Radiography ; }, abstract = {Malignant mesotheliomas are generally considered pathognomonic of asbestos exposure. The prognosis of mesothelioma varies with clinical staging of the disease. The overall survival of patients from the time of diagnosis is six to 16 months. Although patients with malignant mesotheliomas often have nonspecific symptoms and signs, occult diffuse pleural mesothelioma is uncommon, and one that occurs in a patient with no evidence of asbestos exposure must be exceedingly rare. Sudden death as the initial manifestation of pleural mesothelioma, to our knowledge, has not been previously reported in the literature. One such unusual case is documented here.}, } @article {pmid2815414, year = {1989}, author = {De Guire, L and Armstrong, B and Case, B and Cyr, D}, title = {[Could the Quebec Tumor Registry be used to identify risks of occupational cancers?].}, journal = {L'union medicale du Canada}, volume = {118}, number = {2}, pages = {65-71}, pmid = {2815414}, issn = {0041-6959}, mesh = {Adolescent ; Adult ; Aged ; Female ; Humans ; Male ; Mesothelioma/epidemiology ; Middle Aged ; Neoplasms/*epidemiology ; Occupational Diseases/*epidemiology ; Quebec/epidemiology ; *Registries ; Reproducibility of Results ; Risk Factors ; }, abstract = {Many countries have used their tumor registries to conduct studies on cancer and occupation. In the past, the Quebec Tumor Registry (QTR) has collected information on occupation of cases. The form currently in use has a space to include this information but it is not mandatory to do so. Among male cases of naso-sinusal, pleural and ocular cancer, diagnosed between 1975 and 1979, and aged 16 to 64, 72% had information on occupation. The occupation registered at the QTR and the occupation given by the case himself during epidemiological studies on bladder cancer and leukemia are respectively the same in 64% and 69% of cases. The association between mesothelioma and work in asbestos related industries was not found in the present study. Explanations and recommendations are given.}, } @article {pmid2770618, year = {1989}, author = {Facchini, U and Branzaglia, P and Marcazzan, MG and Camnasio, M and Riboldi, L and Bertazzi, PA}, title = {[Mortality caused by pleural mesothelioma in the 1979-1983 lustre in Italy regarding provinces and single local health districts].}, journal = {La Medicina del lavoro}, volume = {80}, number = {2}, pages = {148-154}, pmid = {2770618}, issn = {0025-7818}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Catchment Area, Health ; *Cause of Death ; Female ; Humans ; Italy ; Male ; Mesothelioma/etiology/*mortality ; Middle Aged ; Occupational Diseases/etiology/*mortality ; Pleural Neoplasms/etiology/*mortality ; }, abstract = {The geographic distribution of deaths from pleural mesothelioma in Italian provinces was analysed over the five-year period 1979-1983. In the provinces where the mortality rates were markedly higher than the national average, a further analysis was made on the data referred to the local health districts (USSL) of each province. It was thus possible, in some cases, to identify small, high risk areas which corresponded, as expected, to the location of large factories or shipyards using asbestos.}, } @article {pmid2770615, year = {1989}, author = {Maltoni, C and Pinto, C and Dominici, R}, title = {[Mesotheliomas among mechanics of the railways in Italy: a current problem].}, journal = {La Medicina del lavoro}, volume = {80}, number = {2}, pages = {103-110}, pmid = {2770615}, issn = {0025-7818}, mesh = {Asbestos/*adverse effects ; Cause of Death ; Humans ; Italy ; Mesothelioma/epidemiology/*etiology/mortality ; Occupational Diseases/epidemiology/*etiology/mortality ; Occupations ; Pleural Neoplasms/epidemiology/*etiology/mortality ; *Railroads ; }, abstract = {Asbestos has been used on rolling stock of the Italian Railways since the 1940's. From the 1950's to the 1970's it was used on a massive scale for the insulation of passenger carriages (up to more than 800 kg per carriage). About 10 years ago, a programme was began to remove asbestos from rolling stock and replace it with glass fibre. We must consider as exposed to the carcinogenic effects of asbestos all mechanics who, during the past years, worked at the Major Repair Workshops (MRW), at the Locomotive Depots (LD) of the State Railways, or in other state or private factories where railway rolling stock insulated with asbestos was built, checked, repaired or demolished, or where asbestos removal operations took place. It has been estimated that the total number of mechanics potentially exposed to asbestos since 1950 in the MRWs alone amounts to more than 25,000. There are about 750 workers presently employed at the Bologna MRW and it has been estimated that the entire cohort of this MRW from the beginning of the 1950's includes about 3,000 people (in excess). In 1986 the Bologna Institute of Oncology reported 6 cases of pleural mesothelioma at the Bologna MRW and 1 at the Rimini MRW. This was the first report of pleural mesotheliomas among railway mechanics in Italy. From 1986 up to the present, other cases of pleural mesothelioma have been recorded among mechanics working on railway rolling stock in the MRW's and in the LD's of the State Railways and in other factories.(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid2649672, year = {1989}, author = {Rudd, R}, title = {Malignant mesothelioma.}, journal = {Journal of the Royal Society of Medicine}, volume = {82}, number = {3}, pages = {126-129}, pmid = {2649672}, issn = {0141-0768}, mesh = {Animals ; Asbestos/adverse effects ; Humans ; *Mesothelioma/etiology/pathology ; }, } @article {pmid2646880, year = {1989}, author = {Davenport, J}, title = {Pleural mesothelioma.}, journal = {American family physician}, volume = {39}, number = {3}, pages = {151-154}, pmid = {2646880}, issn = {0002-838X}, mesh = {Aged ; Asbestos/adverse effects ; Humans ; Male ; Mesothelioma/*diagnosis/epidemiology/etiology ; Occupational Diseases/epidemiology/etiology ; Pleural Neoplasms/*diagnosis/epidemiology/etiology ; }, abstract = {The incidence of pleural mesothelioma will probably increase into the next century. A complete occupational history should include an inquiry about asbestos exposure, especially in patients with chest pain or dyspnea. The latency period between exposure and mesothelioma is as long as 50 years. In some patients, early diagnosis leads to a chance of cure. In most cases, however, there is no cure. Accurate diagnosis and a frank discussion of prognosis will allow patients to prepare for death.}, } @article {pmid2546067, year = {1989}, author = {Jagirdar, J and Frydman, C and Sakurai, H and Dumitrescu, O}, title = {Mesothelial papillary proliferation of the pleura associated with radiation therapy: does it have a role in the pathogenesis of mesothelioma?.}, journal = {The Mount Sinai journal of medicine, New York}, volume = {56}, number = {2}, pages = {147-149}, pmid = {2546067}, issn = {0027-2507}, mesh = {Aged ; Carcinoma, Non-Small-Cell Lung/radiotherapy ; Epithelium/pathology/radiation effects ; Humans ; Hyperplasia ; Lung Neoplasms/radiotherapy ; Male ; Mesothelioma/*etiology ; Neoplasm Metastasis ; Neoplasms, Radiation-Induced/*etiology ; Pleura/*pathology/radiation effects ; }, abstract = {Diffuse papillary proliferation of mesothelial cells in the pleura mimicking metastatic carcinoma was seen four weeks following radiation therapy for a Pancoast tumor. Such papillary proliferations are not observed incidentally and are envisioned to occur during asbestos-induced carcinogenesis. We postulate that similar papillary lesions may serve as a link in the pathogenesis of radiation-induced mesotheliomas.}, } @article {pmid2539183, year = {1989}, author = {Newhouse, ML and Sullivan, KR}, title = {A mortality study of workers manufacturing friction materials: 1941-86.}, journal = {British journal of industrial medicine}, volume = {46}, number = {3}, pages = {176-179}, pmid = {2539183}, issn = {0007-1072}, mesh = {Asbestos/*adverse effects ; Asbestos, Serpentine ; Asbestosis/mortality ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/mortality ; Male ; Mesothelioma/mortality ; Occupational Diseases/*mortality ; Pleural Neoplasms/mortality ; Respiratory Tract Diseases/mortality ; Time Factors ; }, abstract = {The mortality of workers employed at a factory producing friction materials has been studied from 1941 to 1986, extending a previous study by seven years. Apart from two periods before 1944, when crocidolite asbestos was used on one particular contract, only chrysotile asbestos has been used. Thirteen deaths were attributed to mesothelioma and of these, 11 were of subjects who had known contact with crocidolite asbestos. Of the remaining two, in one instance the diagnosis is uncertain and in the other the occupational history of the subject is not well established. There was no excess of deaths from lung cancer or other asbestos related tumours, or from chronic respiratory disease. After 1950 hygienic control was progressively improved and from 1970 levels of asbestos in air have not exceeded 0.5-1.0 f/ml. It is concluded that with good environmental control chrysotile asbestos may be used in manufacture without causing excess mortality.}, } @article {pmid2532380, year = {1989}, author = {Britton, M}, title = {Compensation for asbestos-related diseases--the U.K. model.}, journal = {Respiratory medicine}, volume = {83}, number = {2}, pages = {95-102}, doi = {10.1016/s0954-6111(89)80221-5}, pmid = {2532380}, issn = {0954-6111}, mesh = {Asbestos/*adverse effects ; Asbestosis/diagnosis/pathology ; Humans ; Insurance Claim Reporting ; Jurisprudence ; Lung Neoplasms/etiology/pathology ; Mesothelioma/diagnosis/etiology ; Occupational Diseases/*etiology ; Pleural Diseases/etiology/pathology ; United Kingdom ; *Workers' Compensation ; }, } @article {pmid2927705, year = {1989}, author = {Foresti, V and Villa, A and Scolari, N and Parisio, E}, title = {[Is malignant mesothelioma of the pleura only an occupational disease?].}, journal = {Minerva medica}, volume = {80}, number = {2}, pages = {145-148}, pmid = {2927705}, issn = {0026-4806}, mesh = {Aged ; Asbestos/adverse effects ; Environmental Pollution/adverse effects ; Female ; Humans ; Italy ; Male ; Mesothelioma/*diagnosis/etiology ; Middle Aged ; Occupational Diseases/*diagnosis/etiology ; Pleural Neoplasms/*diagnosis/etiology ; Retrospective Studies ; Risk Factors ; Smoking/adverse effects ; }, abstract = {Ten cases of pleural malignant mesothelioma identified histologically at the Department of General Medicine in May 1983-June 1987, are examined in this paper. Occupational risk factors and clinical features are discussed. Only one patient (10%) was subjected to occupational risk of asbestos exposure (as a smith) while the other nine patients showed a negative anamnesis for direct or indirect asbestos exposure. However, one of these patients was a tram-driver. The patients' mean age was 69 years old. 7 patients were males. 7 patients were born in an industrialized urban environment, 3 were born in an agricultural environment: all had been living in Milan for many years. Pleural fluid cytology was only useful in the diagnosis of 2 cases. This study suggests that pleural malignant mesothelioma is a neoplasm which also affects people not exposed to asbestos at work and that its frequency is increasing. The most probable cause is environmental contamination by asbestos of urban industrialized areas. Thus, it is necessary to eliminate this mineral from all manufacturing processes in which asbestos is not indispensable.}, } @article {pmid2923830, year = {1989}, author = {Raffn, E and Lynge, E and Juel, K and Korsgaard, B}, title = {Incidence of cancer and mortality among employees in the asbestos cement industry in Denmark.}, journal = {British journal of industrial medicine}, volume = {46}, number = {2}, pages = {90-96}, pmid = {2923830}, issn = {0007-1072}, mesh = {Asbestos/*adverse effects ; Cohort Studies ; Denmark ; Female ; Humans ; Lung Neoplasms/epidemiology/etiology ; Male ; Neoplasms/*epidemiology/etiology/mortality ; Occupational Diseases/*epidemiology/etiology/mortality ; }, abstract = {In a cohort study of the incidence of cancer and mortality among 7996 men and 584 women employed in the Danish asbestos cement industry between 1928 and 1984 over 99% were traced. Chrysotile asbestos was the only fibre type used until 1946, when amosite and (in 1952) crocidolite were also introduced. Chrysotile constituted 89%, amosite 10%, and crocidolite 1% of the asbestos used. During the first 25 years of manufacture the exposure levels were high, especially in areas where the asbestos was handled dry. Measurements from 1948 indicate that the fibre levels may have ranged from 100 to 1600 times over the present Danish threshold limit value of 0.5 fibre/ml. In 1973 more than 41% of personal samples were higher than 2 f/ml. About 76% of the workforce left the factory within five years of starting employment. A total of 1346 deaths and 612 cases of cancer were observed in the cohort between 1943 and 1984. Among employed men the overall mortality (O/E 1.18; 95% CI 1.12-1.25), cancer mortality (O/E 1.32; 95% CI 1.19-1.46), and overall incidence of cancer (O/E 1.22; 95% CI 1.12-1.32) were significantly increased compared with all Danish men. This was not so among employed women. For men, significant excess risks were found for cancer of the lung (O/E 1.80; 95% CI 1.54-2.10), pleura (O/E 5.46; 95% CI 2.62-10.05), mediastinum (O/E 5.00; 95% CI 1.01-14.61), stomach (O/E 1.43; 95% CI 1.03-1.93), and other male genital organs (O/E 3.03; 95% CI 1.11-6.60). The mortality was significantly increased for men for non-malignant pulmonary diseases (O/E 1.63; 95% CI 1.33-1.98). Among the group of asbestos cement workers with first employment 1928-40 an excess risk of laryngeal cancer was found (O/E 5.50;95% CI 1.77-12.82). A total of 12 cases of pleural and one of peritoneal mesotheliomas was observed when the original notification forms were reviewed for all patients with cancer in the cohort.}, } @article {pmid2922588, year = {1989}, author = {Hansen, ES}, title = {Mortality of auto mechanics. A ten-year follow-up.}, journal = {Scandinavian journal of work, environment & health}, volume = {15}, number = {1}, pages = {43-46}, doi = {10.5271/sjweh.1883}, pmid = {2922588}, issn = {0355-3140}, mesh = {Adolescent ; Adult ; Aged ; *Automobiles ; Cardiovascular Diseases/mortality ; Cohort Studies ; Coronary Disease/etiology/*mortality ; Denmark ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Neoplasms/etiology/*mortality ; Occupational Diseases/etiology/*mortality ; }, abstract = {This study was set up to investigate whether work in car repair workshops is associated with an increased risk of ischemic heart disease and specific malignant neoplasms. For this purpose, a cohort of auto mechanics has been followed through 10 years with regard to cause-specific mortality. Comparisons were made with another cohort of skilled male workers who were not exposed to asbestos or petrochemical substances. The auto mechanics' mortality was increased for ischemic heart disease [standardized mortality ratio (SMR) 121, 95% confidence interval (95% CI) 102-145], other cardiovascular diseases (SMR 112, 95% CI 82-150), cancer (SMR 115, 95% CI 97-136), other diseases (SMR 119, 95% CI 94-149), and external causes (SMR 131, 95% CI 113-153). For specific cancer sites, increases were seen for pancreatic cancer, urinary cancer outside the bladder, and pleural mesothelioma.}, } @article {pmid2914699, year = {1989}, author = {Hammar, SP and Bockus, D and Remington, F and Freidman, S and LaZerte, G}, title = {Familial mesothelioma: a report of two families.}, journal = {Human pathology}, volume = {20}, number = {2}, pages = {107-112}, doi = {10.1016/0046-8177(89)90173-1}, pmid = {2914699}, issn = {0046-8177}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Environmental Exposure ; Humans ; Lung Neoplasms/chemically induced/genetics/*pathology ; Male ; Mesothelioma/chemically induced/genetics/*pathology ; Middle Aged ; Pedigree ; Peritoneal Neoplasms/chemically induced/genetics/*pathology ; Retroperitoneal Neoplasms/chemically induced/genetics/*pathology ; }, abstract = {Five reports of familial mesothelioma in which mesotheliomas occurred in two or more family members have been recorded in the medical literature. In this report, we describe two examples of familial mesothelioma. In one family, three brothers who worked in the asbestos insulation industry developed mesothelioma. In the second family, the father, who was occupationally exposed to asbestos, died from a tubulopapillary peritoneal mesothelioma 11 years before his son died from an identical histologic type of peritoneal mesothelioma. Our report, as with those previously recorded, suggests that genetic factors may be important in the genesis of some mesotheliomas.}, } @article {pmid2914565, year = {1989}, author = {Kishimoto, T and Okada, K and Sato, T and Ono, T and Ito, H}, title = {Evaluation of the pleural malignant mesothelioma patients with the relation of asbestos exposure.}, journal = {Environmental research}, volume = {48}, number = {1}, pages = {42-48}, doi = {10.1016/s0013-9351(89)80083-0}, pmid = {2914565}, issn = {0013-9351}, mesh = {Aged ; Asbestos/*adverse effects ; Female ; Humans ; Male ; Mesothelioma/*etiology ; Middle Aged ; Occupational Diseases/etiology ; Pleural Neoplasms/*etiology ; }, abstract = {There has been a recent increase in the number of patients with malignant mesothelioma in parts of Japan where Naval shipyards were located during World War II. This can be attributed to asbestos exposure during work in the shipyard. We have studied eight patients who were seen between 1984 and 1986 in Kure Kyosai Hospital. All had a history of asbestos exposure, seven in a Naval shipyard. In these seven cases, the latent period between exposure and the appearance of mesothelioma was 43-49 years. Quantification of asbestos bodies in the lung indicated a high concentration in all patients, giving further weight to the concept that asbestos is an etiologic factor in the genesis of mesothelioma. The major types of asbestos fibers were crocidolite and amosite. The study of structural features of these two types may provide a clue to the pathogenesis of the disease.}, } @article {pmid2717559, year = {1989}, author = {Boutin, C}, title = {Thoracoscopy in malignant mesothelioma.}, journal = {Pneumologie (Stuttgart, Germany)}, volume = {43}, number = {2}, pages = {61-65}, pmid = {2717559}, issn = {0934-8387}, mesh = {Biopsy ; Humans ; Mesothelioma/*diagnosis ; Neoplasm Staging ; Pleura/pathology ; Pleural Neoplasms/*diagnosis ; *Thoracoscopy ; }, abstract = {Thoracoscopy is a suitable diagnostic method in malignant mesothelioma, since it enables simultaneously histopathological diagnosis, identification of asbestos fibres, staging of tumour spread, and pleurodesis therapy.}, } @article {pmid2920147, year = {1989}, author = {Huncharek, M and Muscat, J and Capotorto, JV}, title = {Pleural mesothelioma in a brake mechanic.}, journal = {British journal of industrial medicine}, volume = {46}, number = {1}, pages = {69-71}, pmid = {2920147}, issn = {0007-1072}, mesh = {Asbestos/*adverse effects ; *Automobiles ; Humans ; Male ; Mesothelioma/*etiology ; Middle Aged ; Occupational Diseases/*etiology ; Pleural Neoplasms/*etiology ; }, } @article {pmid2818230, year = {1989}, author = {Kheĭtov, LK}, title = {[Further comment on mesotheliomas].}, journal = {Arkhiv patologii}, volume = {51}, number = {8}, pages = {62-65}, pmid = {2818230}, issn = {0004-1955}, mesh = {Diagnosis, Differential ; Female ; Heart Neoplasms/diagnosis/*pathology ; Humans ; Lymphatic Metastasis ; Male ; Mesothelioma/diagnosis/*pathology ; Middle Aged ; Pericardium/pathology ; }, abstract = {11 cases of malignant mesothelioma (0.153%) were among 7184 autopsies in Tambov Bureau of Pathology from 1978 to 1987. There were 4 cases of pleural mesothelioma (0.055%), 5 cases of pericardial mesothelioma (0.069%), one case of peritoneal mesothelioma and one case of a simultaneous involvement of the peritoneum, pleura and pericardium. Two cases of malignant epithelioid mesothelioma of the pericardium are described, which characterized by a diffuse growth along both surfaces of the pericardium with the accumulation in its cavity of two litres of hemorrhagic liquid. In the case of a 50-year-old man who had a contact with asbestos the tumour grew into the coronary artery resulting in clinical symptoms and morphology of the myocardial infarction. Metastases were found in the anterior mediastinal lymph nodes only. In the second case-that of a 48-year-old women--there were metastases in the regional lymph nodes, pleura, the lung and liver.}, } @article {pmid2784625, year = {1989}, author = {Hessel, PA and Sluis-Cremer, GK}, title = {X-ray findings, lung function, and respiratory symptoms in black South African vermiculite workers.}, journal = {American journal of industrial medicine}, volume = {15}, number = {1}, pages = {21-29}, doi = {10.1002/ajim.4700150104}, pmid = {2784625}, issn = {0271-3586}, mesh = {Adult ; Asbestosis/diagnostic imaging/epidemiology/physiopathology ; Cross-Sectional Studies ; Forced Expiratory Volume/methods/statistics & numerical data ; Humans ; Lung/*physiopathology ; Male ; Mining ; Pneumoconiosis/diagnostic imaging/epidemiology/*physiopathology ; Radiography ; Smoking/adverse effects ; South Africa ; Time Factors ; Vital Capacity ; }, abstract = {Health effects have been documented among American vermiculite workers who mined and processed vermiculite contaminated with amphibole asbestos, viz., tremolite-actinolite. Workers mining and processing South Africa vermiculite (N = 172), which contains very little asbestos, underwent x-ray examination and lung function testing and completed a respiratory symptom questionnaire. The vermiculite workers were compared with other workers involved in the mining or refining of copper. Only two of the vermiculite workers showed evidence of small opacities of 1/0 or more (according to the ILO 1980 classification); lung function was comparable with the other groups of workers, and there was no excess of respiratory symptoms among the vermiculite workers. It is concluded that workers exposed to vermiculite that is minimally contaminated with asbestos are probably not at risk for pneumoconiosis, lung function impairment, or respiratory symptoms. It is likely that the health effects observed in other studies of vermiculite workers are the result of concomitant asbestos exposure. A risk of mesothelioma caused by the fiber content of the vermiculite cannot be excluded by this study.}, } @article {pmid2782316, year = {1989}, author = {Finkelstein, MM}, title = {Mortality among employees of an Ontario factory that manufactured construction materials using chrysotile asbestos and coal tar pitch.}, journal = {American journal of industrial medicine}, volume = {16}, number = {3}, pages = {281-287}, doi = {10.1002/ajim.4700160306}, pmid = {2782316}, issn = {0271-3586}, mesh = {Adult ; Asbestos/*adverse effects ; Coal Tar/*adverse effects ; Cohort Studies ; Genital Neoplasms, Male/etiology/*mortality ; Humans ; Lung Neoplasms/etiology/*mortality ; Male ; Mesothelioma/etiology/*mortality ; Middle Aged ; Occupational Diseases/*mortality ; Ontario ; }, abstract = {This paper describes mortality in a cohort of 324 men exposed to chrysotile asbestos and coal tar pitch used in the manufacture of electrical conduit pipe from a mixture of newsprint, bentonite, and asbestos. One death in a factory worker was attributed to pleural mesothelioma, and long-term employees experienced an increased risk of lung cancer (Standardized Mortality Ratio (SMR) 221; six deaths) and non-malignant respiratory disease (SMR 215; four deaths). In a case-control analysis, men whose jobs involved adding asbestos to the mix of raw materials were found to have a risk of lung cancer sevenfold higher (lower 95% confidence limit: 2.3) than men who had never worked at this job. Exposure to coal tar pitch is presumed to be responsible for the death of one worker from squamous cell carcinoma of the scrotum.}, } @article {pmid2782313, year = {1989}, author = {Tuomi, T and Segerberg-Konttinen, M and Tammilehto, L and Tossavainen, A and Vanhala, E}, title = {Mineral fiber concentration in lung tissue of mesothelioma patients in Finland.}, journal = {American journal of industrial medicine}, volume = {16}, number = {3}, pages = {247-254}, doi = {10.1002/ajim.4700160303}, pmid = {2782313}, issn = {0271-3586}, mesh = {Adolescent ; Adult ; Aged ; Asbestos/adverse effects/*isolation & purification ; Environmental Exposure ; Finland ; Humans ; Lung/*analysis ; Male ; Mesothelioma/etiology/*pathology ; Microscopy, Electron, Scanning ; Middle Aged ; Occupations ; }, abstract = {The mineral fibers in lung tissue samples of 19 mesothelioma patients and 15 randomly selected autopsy cases were analyzed using low-temperature ashing, scanning electron microscopy (SEM) and x-ray microanalysis. The fiber concentration ranged from 0.5 to 370 million fibers per gram of dry tissue in the mesothelioma group and from less than 0.01 to 3.2 million fibers per gram of dry tissue in the autopsy group. In 80% of the mesothelioma patients and in 20% of the autopsy cases, the fiber concentration exceeded 1 million fibers per gram of dry tissue. Amphibole asbestos fibers predominated in both groups, and only a few chrysotile fibers were found. In the lungs of six mesothelioma patients, anthophyllite was the main fiber type. The overall analytical precision of sample preparation and fiber counting with SEM was 22%.}, } @article {pmid2744843, year = {1989}, author = {Commins, BT}, title = {Estimations of risk from environmental asbestos in perspective.}, journal = {IARC scientific publications}, volume = {}, number = {90}, pages = {476-485}, pmid = {2744843}, issn = {0300-5038}, mesh = {Air Pollutants/*adverse effects/analysis ; Asbestos/*adverse effects/analysis ; Gastrointestinal Neoplasms/etiology ; Humans ; Lung Diseases/epidemiology/etiology ; Lung Neoplasms/*etiology ; Occupational Diseases/etiology ; Risk ; Water Pollutants, Chemical/adverse effects ; }, abstract = {Because very recent data on asbestos in the environment are available, some fairly firm conclusions can now be drawn regarding current exposure to asbestos fibres. If account is taken of occupational exposure data (where past exposure levels were very high indeed, leading to a very significant risk to workers at the time), it is possible to make some reasoned estimates of the risk from ambient air. In the past, there was considerable confusion regarding the degree of risk for both occupational and environmental conditions. In estimating the risk, account needs to be taken, in particular, of the fact that: (a) occupational exposures in the past were frequently higher than reported; (b) asbestosis (a disease only associated with very heavy occupational exposures) would seem to be mechanistically involved in the development of lung cancer associated with asbestos exposure; (c) chrysotile asbestos is now the commonest form of fibre used unlike in the past, when greater quantities of crocidolite and amosite were used, the latter types being much more closely associated with mesothelioma than chrysotile; (d) overall levels of asbestos in environmental ambient air are lower than they used to be; (e) ingested asbestos seems to be associated with a negligible degree of risk as indicated by animal and human studies. The estimated values of risk provided here are smaller than those published some years ago but are similar to those given in very recent key publications. The level of environmental lifetime risk from exposure to airborne asbestos would appear to be about 1 in 100,000 or even lower. Such a level of risk is exceedingly low, and bearing in mind the criteria of both WHO and the Royal Society of London, it would appear to represent an acceptable 'rare-event' extremely low-level risk, like the cancer risk from the cosmic radiation adsorbed when flying across the Atlantic or from eating charcoal broiled meat, or the risk of being killed by lightning.}, } @article {pmid2744842, year = {1989}, author = {Hughes, JM and Weill, H}, title = {Development and use of asbestos risk estimates.}, journal = {IARC scientific publications}, volume = {}, number = {90}, pages = {471-475}, pmid = {2744842}, issn = {0300-5038}, mesh = {Adult ; Asbestos/*adverse effects ; Child ; Environmental Exposure ; Female ; Humans ; Lung Neoplasms/*etiology ; Male ; Mesothelioma/*etiology ; Risk ; Schools ; Smoking/adverse effects ; }, abstract = {Several groups of researchers, at the request of government agencies in various countries, have reviewed the literature on the health effects of asbestos exposure and derived quantitative estimates of the risks from such exposures. Because of differences in the area of responsibility of the different agencies, these estimates have inevitably been based on different assumptions concerning exposure (concentration, number of years of exposure, initial age, and number of hours per week). The lifetime cancer risk estimates derived in 6 reports are compared here, after adjustment to a common set of exposure assumptions appropriate for students attending schools containing asbestos products. Estimates are found to be reasonably similar, remaining differences being primarily due to differences in assumptions concerning parameter values of the models and the background risk of lung cancer. The various administrative processes used by the US agencies are also compared, and recommendations made for US government agencies involved in the derivation of risk estimates for exposures of general public concern.}, } @article {pmid2744838, year = {1989}, author = {McDonald, JC and Sébastien, P and McDonald, AD and Case, B}, title = {Epidemiological observations on mesothelioma and their implications for non-occupational exposure.}, journal = {IARC scientific publications}, volume = {}, number = {90}, pages = {420-427}, pmid = {2744838}, issn = {0300-5038}, mesh = {Air Pollutants/*adverse effects/analysis ; Asbestos/adverse effects/analysis ; Dust/analysis ; Female ; Hazardous Substances/*adverse effects/analysis ; Humans ; Lung/analysis ; Male ; Mesothelioma/*epidemiology/etiology/mortality ; Mining ; Particle Size ; Pleural Neoplasms/*epidemiology/etiology/mortality ; }, } @article {pmid2729290, year = {1989}, author = {McDonald, C and McDonald, A}, title = {Mesothelioma in railroad workers.}, journal = {American journal of industrial medicine}, volume = {15}, number = {4}, pages = {487-490}, doi = {10.1002/ajim.4700150414}, pmid = {2729290}, issn = {0271-3586}, mesh = {Asbestos/*adverse effects ; Cohort Studies ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; *Railroads ; }, } @article {pmid2729289, year = {1989}, author = {Finkelstein, MM}, title = {Mortality among employees of an Ontario factory manufacturing insulation materials from amosite asbestos.}, journal = {American journal of industrial medicine}, volume = {15}, number = {4}, pages = {477-481}, doi = {10.1002/ajim.4700150411}, pmid = {2729289}, issn = {0271-3586}, mesh = {Asbestosis/epidemiology/*mortality ; Cohort Studies ; Health Status Indicators ; Humans ; Male ; *Occupational Medicine ; Ontario ; Quality Control ; }, abstract = {The mortality of workers from an Ontario factory manufacturing amosite asbestos insulation materials under poorly controlled environmental conditions is reported here. Seven (58%) of 12 deaths among exposed workers 10 or more years after first exposure were due to malignancies; four (25%) were from lung cancer, and there were two deaths from peritoneal mesothelioma. Those dying from mesothelioma were 47 and 49 years of age. Three (25%) of 12 deaths were from respiratory disease, two were attributed to asbestosis (in men 42 and 53 years of ages), and one to pneumonia in a 54-year-old male.}, } @article {pmid2699035, year = {1989}, author = {Cooper, SP and Fraire, AE and Buffler, PA and Greenberg, SD and Langston, C}, title = {Epidemiologic aspects of childhood mesothelioma.}, journal = {Pathology and immunopathology research}, volume = {8}, number = {5-6}, pages = {276-286}, doi = {10.1159/000157156}, pmid = {2699035}, issn = {0257-2761}, mesh = {Adolescent ; Asbestos/adverse effects ; Child ; Child, Preschool ; Cohort Studies ; Death Certificates ; Diagnostic Errors ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Mesothelioma/diagnosis/*epidemiology/etiology/pathology ; Texas/epidemiology ; United States/epidemiology ; }, abstract = {Our calculation provides the first population-based incidence rate of childhood mesothelioma in the United States. Based on these data and on our pathology review, we conclude that mesothelioma occurs rarely in children and that this diagnosis is difficult to establish. A more systematic approach to identifying mesothelioma cases in children, as well as adults, will be facilitated by increasing state surveillance of cancer incidence and by the proposed addition of a unique code for mesothelioma in the Tenth Revision of the ICD. There is a critical need for histopathological verification of mesothelioma cases. The increased use of a uniform, reproducible histopathologic classification and mesothelioma panels should address this problem. A thorough microscopic study of individual cases needs to be supplemented by a careful assessment of the clinical findings and environmental factors. The available data thus far do not support an association between childhood mesothelioma and asbestos exposure. However, the ubiquitous nature of asbestos exposures, the known association of asbestos with adult mesothelioma, the unreliability of the diagnosis, and the lack of adequate data regarding asbestos exposures, all indicate that asbestos involvement cannot be categorically ruled out, especially in older children with the potential for a longer duration of exposure and a plausible induction period. Mesothelioma in children, as well as in adults, is likely to have a multifactorial etiology. Radiation, prenatal medications, and genetic factors are all possible etiologic agents in childhood mesothelioma. In addition, other, as of yet unspecified environmental factors may play a role in this disease. When cases are diagnosed, the physician should inquire about the history of exposure to asbestos or other hazardous materials in the patient's environment, prior radiation exposure, medication exposure pre- and postnatally, prior cancer diagnoses, and a family history of cancer. An interdisciplinary approach, combining the diagnostic skills of the pathologist and the analytic skills of the epidemiologist, will be of value and of special relevance in the study of mesotheliomas.}, } @article {pmid2690716, year = {1989}, author = {Timbrell, V}, title = {Review of the significance of fibre size in fibre-related lung disease: a centrifuge cell for preparing accurate microscope-evaluation specimens from slurries used in inoculation studies.}, journal = {The Annals of occupational hygiene}, volume = {33}, number = {4}, pages = {483-505}, doi = {10.1093/annhyg/33.4.483}, pmid = {2690716}, issn = {0003-4878}, mesh = {Animals ; Centrifugation/instrumentation ; Lung Diseases/*etiology ; Mesothelioma/*etiology ; Minerals/*analysis/toxicity ; Particle Size ; }, abstract = {Intratracheal, intrapleural and intraperitoneal inoculation studies in animals are widely used for identifying important factors in the pathogenicity of fine fibrous particles and estimating the potential of new materials to produce human pulmonary disease. Evidence on the significance of fibre size is reviewed, with emphasis on direct data derived from airborne fibres in asbestos mines and fibres retained in the mineworkers' lungs. This evidence indicates a need in mesothelioma-related inoculation experiments for means of measuring fibres down to 0.01 microns in diameter. A test cell, developed for preparing microscope-evaluation specimens from injection slurries, has a sector-shaped sedimentation chamber and is used in a swing-rotor centrifuge. To minimize re-formation of aggregates that are dispersed by shearing forces during sedimentation, a sample of the slurry is diluted beforehand to a degree indicated by the length of the longest fibres seen in the light microscope. Fibres and other particles are collected as a uniform deposit on a collodion film enveloping a microscope cover-glass. Current techniques are used to prepare specimens from films for light microscopy, scanning electron microscopy and the transmission electron microscopy which is so necessary for measurement of very fine fibres. Applications of the cell to fibre samples from other sources are outlined.}, } @article {pmid2672801, year = {1989}, author = {Smith, AH and Shearn, VI and Wood, R}, title = {Asbestos and kidney cancer: the evidence supports a causal association.}, journal = {American journal of industrial medicine}, volume = {16}, number = {2}, pages = {159-166}, doi = {10.1002/ajim.4700160207}, pmid = {2672801}, issn = {0271-3586}, mesh = {Animals ; Asbestos/*adverse effects ; Cohort Studies ; Female ; Humans ; Italy ; Kidney Neoplasms/*etiology ; Male ; Occupational Diseases/*etiology ; United States ; }, abstract = {The role of asbestos in the etiology of lung cancer and of mesothelioma of the pleura and peritoneum has been well documented. The evidence for a causal association between asbestos and other human cancers is not as extensive but suggests that asbestos may be carcinogenic at several different sites. This paper is concerned specifically with a possible causal association between asbestos and human kidney cancer. A review of the evidence to date indicates that only three human studies have sufficient statistical power to detect an excess mortality from kidney cancer among workers exposed to asbestos. All three were occupational cohort studies, and two of these gave strong direct evidence for such an excess; a study of U.S. insulators (kidney cancer SMR = 2.22, 90% CI 1.44-3.30), and a study of U.S. asbestos products company workers (kidney cancer SMR = 2.76, 90% CI 1.29-5.18). The third study, of Italian shipyard workers, reported excess mortality from "cancers of the kidney, urinary bladder, and other urinary organs" (SMR = 1.98, 90% CI 1.42-2.70). Further support for a causal association includes studies finding asbestos fibers in human kidneys and urine, as well as reports of kidney tumors in two animal bioassays. It is concluded that asbestos should be regarded as a probable cause of human kidney cancer.}, } @article {pmid2663717, year = {1989}, author = {Gardner, MJ and Saracci, R}, title = {Effects on health of non-occupational exposure to airborne mineral fibres.}, journal = {IARC scientific publications}, volume = {}, number = {90}, pages = {375-397}, pmid = {2663717}, issn = {0300-5038}, mesh = {Air Pollutants/*adverse effects ; Asbestos/adverse effects ; Epidemiologic Methods ; Hazardous Substances/*adverse effects ; Humans ; Lung Neoplasms/*epidemiology/mortality ; Mesothelioma/*epidemiology ; Minerals/*adverse effects ; Pleural Neoplasms/*epidemiology ; }, abstract = {The most prominent potential marker of disease-related non-occupational exposure to mineral fibres is mesothelioma. Although many cases of mesothelioma have resulted from occupational exposure to asbestos, some have been associated with para-occupational domestic and/or neighbourhood exposure and have been reported in case series, case-control studies and a cohort study among non-occupationally exposed subjects. However, little information is available on mesothelioma as a direct consequence of general environmental asbestos exposure. Such cases of mesothelioma related to non-occupational exposure to asbestos as have occurred to date are likely to have resulted from past exposures much higher than those prevailing at the present time (in the developed countries); numbers will therefore probably decrease in the future. Very high rates of mesothelioma have been reported as a result of exposure to erionite. No studies are available on the effects of non-occupational exposure to man-made mineral fibres but, among occupationally exposed workers, a risk of mesothelioma is not apparent. There are suggestions of raised lung cancer rates among household contacts of asbestos workers and among individuals exposed to erionite. Non-malignant parenchymal and pleural abnormalities have been observed in subjects exposed non-occupationally to asbestos and erionite, but these are not necessarily associated with malignant lesions. Quantitative risk estimates of adverse effects on health have not been derived from these studies, essentially because of the absence of fibre exposure measurements.}, } @article {pmid2663716, year = {1989}, author = {Davis, JM}, title = {Mineral fibre carcinogenesis: experimental data relating to the importance of fibre type, size, deposition, dissolution and migration.}, journal = {IARC scientific publications}, volume = {}, number = {90}, pages = {33-45}, pmid = {2663716}, issn = {0300-5038}, mesh = {Animals ; Asbestos/*adverse effects/analysis ; Carcinogens, Environmental/*adverse effects ; Dust/adverse effects ; Humans ; Lung/analysis ; Neoplasms/*etiology ; Particle Size ; }, abstract = {Fibre type, fibre size, deposition, dissolution and migration are all factors of importance in mineral fibre carcinogenesis. These factors are, however, so interrelated that only fibre size can be considered on its own to any extent. When dusts are injected into the pleural or peritoneal cavities, the most carcinogenic samples, producing the most mesotheliomas, are those containing the most long, thin fibres. When very short fibre samples of both amosite and chrysotile recently became available for comparison with long fibre preparations of the same materials, short fibres were found to be much less fibrogenic and carcinogenic than long fibres. The same studies provided important information on fibre deposition and dissolution. Short fibre samples of both asbestos varieties penetrated to the pulmonary parenchyma more easily than long ones but, after deposition, short fibres were cleared more quickly. Very much less chrysotile was present in lung tissue at the end of one year's dusting and clearance during the following 6 months was very much faster. The long fibre chrysotile, which would be expected to be resistant to mechanical clearance, was removed from the lungs much more quickly than short fibre amosite, which was easily phagocytosed by macrophages. This indicates that rapid chrysotile removal from lung tissue is due at least in part to fibre dissolution. The phenomenon of chrysotile dissolution probably explains why this asbestos type has been shown to be extremely carcinogenic in rats but seems less carcinogenic than the amphiboles in humans. Fibres may remain in lung tissue for the 1-2 years necessary to cause tumours in rats but this is too short a time for the much longer lived humans. Only very few fibres penetrate the walls of the gut following massive asbestos ingestion, although a few of these can subsequently be found disseminated to other organs. Fibres are disseminated to other organs much more effectively after inhalation. One area where fibre dissemination has been suggested as being very important is that of transport from the lung tissue to the pleural cavity, but in rats, direct fibre penetration to the pleura occurs very rarely and the exact mechanism by which inhaled fibres reach the sites where they can produce mesotheliomas remains one of the most important subjects for future research.}, } @article {pmid2649425, year = {1989}, author = {Montizaan, GK and Knaap, AG and Van der Heijden, CA}, title = {Asbestos: toxicology and risk assessment for the general population in The Netherlands.}, journal = {Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association}, volume = {27}, number = {1}, pages = {53-63}, doi = {10.1016/0278-6915(89)90093-8}, pmid = {2649425}, issn = {0278-6915}, mesh = {Asbestos/*toxicity ; *Health Surveys ; Humans ; Netherlands ; Risk Factors ; }, abstract = {Within the scope of the preparation of Integrated Criteria Documents for priority compounds in The Netherlands, the possible health effects of oral and inhalatory exposure to asbestos for the general population were evaluated. It was concluded from the results of experiments in animals that exposure to asbestos by the oral route is not carcinogenic and is not expected to present a health risk to the general population. Inhaled asbestos, however, is distinctly carcinogenic to man, giving rise to lung tumours, and mesotheliomas of the pleura and peritoneum. Chrysotile asbestos appears to be less potent in inducing mesotheliomas than the amphiboles, but all types of asbestos appear to have a similar potency for inducing lung cancer. The risk of mesothelioma is not expected to be influenced by smoking, whereas the risk of lung cancer is expected to be ten times higher in smokers than in non-smokers exposed to the same asbestos concentrations. Risk-assessment models for the inhalatory route, for the general population, are based on linear non-threshold extrapolation of occupational exposure to much lower environmental concentrations. These models give only a rough approximation of the risk of environmental exposure to asbestos. In accordance with the Air Quality Guidelines of the World Health Organization (World Health Organization, 1987), it was estimated that an extra risk of lung cancer of one in 10(6) (in the general population, with 30% smokers) may be presented by lifetime exposure to asbestos fibres longer than 5 microns, measured by electron microscopy, at concentrations of 100-1000/m3. It was further estimated that an extra risk of mesothelioma of one in 10(6) may be presented by lifetime exposure to 10-100 amphibole fibres/m3 or to a range of 100-10000 chrysotile fibres/m3 (fibres longer than 5 microns). From the current asbestos concentrations, the risk of mesothelioma for the general population in The Netherlands appears to be negligible; the extra risk of lung cancer is expected to be higher than 1 in 10(6) near asbestos sources, whereas it appears to be negligible in background areas and in most large cities and industrial areas. However, it must be borne in mind that the validity of the risk figures given is difficult to judge.}, } @article {pmid2643716, year = {1989}, author = {Gamsu, G and Aberle, DR and Lynch, D}, title = {Computed tomography in the diagnosis of asbestos-related thoracic disease.}, journal = {Journal of thoracic imaging}, volume = {4}, number = {1}, pages = {61-67}, doi = {10.1097/00005382-198901000-00012}, pmid = {2643716}, issn = {0883-5993}, mesh = {Asbestosis/*diagnostic imaging ; Humans ; Lung Neoplasms/*diagnostic imaging ; Mesothelioma/*diagnostic imaging ; Pleural Diseases/*diagnostic imaging ; *Tomography, X-Ray Computed ; }, abstract = {High-resolution computed tomography (HRCT) has improved the radiologist's ability to detect and potentially quantify the abnormalities of asbestos exposure. It has proved to be more sensitive than chest radiography for detecting pleural plaques and for discriminating between pleural fibrosis and extrapleural fat. HRCT is also more sensitive than chest radiography or conventional CT for detecting parenchymal abnormalities in asbestos-exposed persons. The HRCT findings that correlate with other parameters of asbestosis include (1) septal and centrilobular thickening, (2) parenchymal fibrous bands, (3) honeycomb patterns, (4) subpleural density persisting in the prone position, and (5) subpleural curvilinear lines that persist in the prone position. CT has an important role in evaluating benign and malignant lung and pleural masses in asbestosis.}, } @article {pmid2620245, year = {1989}, author = {Kishimoto, T and Sato, T and Ono, T and Okada, K and Masuda, Y and Ito, H}, title = {Malignant mesotheliomas in Kure City, Japan: the relationship of asbestos exposure.}, journal = {Cancer investigation}, volume = {7}, number = {5}, pages = {407-410}, doi = {10.3109/07357908909041370}, pmid = {2620245}, issn = {0735-7907}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Environmental Exposure ; Female ; Humans ; Japan ; Male ; Mesothelioma/*etiology ; Middle Aged ; Occupational Diseases/*etiology ; Pleural Neoplasms/*etiology ; }, abstract = {Eighteen patients with malignant mesothelioma were seen at Kure Mutual Aid Hospital over a 10-year period. According to occupational history, chest x-ray manifestations, and evidence of asbestos bodies in the tissue, 13 of these cases were definitely thought to be due to exposure to asbestos as a result of two or three of these items testing positive. Kure City is one of the major ship-building cities in Japan since the 1920s. Most of the 18 patients worked in ship building before and during World War II. Malignant mesothelioma appeared about 40 years after their first exposure to asbestos. In western countries, most malignant mesotheliomas are thought to be induced by exposure to asbestos fibers (1,2). Consequently, there has been a serious effort to deal with this problem recently, including lowering rate of exposure. In Japan, however, there have been few reports that asbestos fibers caused malignant mesothelioma (3). This report suggests that an increased incidence of malignant mesotheliomas in a specific area of Japan may also be due to exposure to asbestos fibers.}, } @article {pmid2612745, year = {1989}, author = {van Gelder, T and Hoogsteden, HC and Versnel, MA and de Beer, PH and Vandenbroucke, JP and Planteydt, HT}, title = {Malignant peritoneal mesothelioma: a series of 19 cases.}, journal = {Digestion}, volume = {43}, number = {4}, pages = {222-227}, doi = {10.1159/000199880}, pmid = {2612745}, issn = {0012-2823}, mesh = {Adult ; Age Factors ; Aged ; Asbestos/*adverse effects ; Ascites/pathology ; Biopsy ; Body Weight ; Environmental Exposure ; Humans ; Laparotomy ; Male ; *Mesothelioma/chemically induced/diagnosis/mortality/therapy ; Middle Aged ; Netherlands ; *Peritoneal Neoplasms/chemically induced/diagnosis/mortality/therapy ; Retrospective Studies ; Time Factors ; }, abstract = {The clinical data, diagnostic procedures and survival are reported in 19 cases diagnosed as malignant peritoneal mesothelioma. All patients were men and 74% had an occupational exposure to asbestos, whereas in 26% no information about asbestos exposure was available. The median interval between asbestos exposure and the diagnosis appeared to be 44.7 years (range 18-49 years). The most common presenting symptoms were abdominal pain, weight loss and dysphagia. Most patients presented with a large amount of ascites. In the majority of patients no therapy except pain relief was given and the median survival from the time of diagnosis was 6 months (range: 0-29 months). Some patients received surgery or chemotherapy, which however did not prolong survival. Only in 2 patients survival exceeded 1 year, although these patients did not receive therapy. The autopsy findings of some patients showed that there were positive abdominal lymph nodes in 2 of them, while in no case positive thoracic lymph nodes were found. The relative short survival period from the time of the first diagnosis in contrast to malignant pleural mesotheliomas is probably the reason for the absence of distant metastases. In this series only in a minority of patients cytology of the ascites was positive and often a laparotomy had to be done. Since cytologic specimens are often negative, we suggest that in patients suspected of a malignant peritoneal mesothelioma, laparoscopy with directed biopsies is the diagnostic procedure of first choice.}, } @article {pmid2610210, year = {1989}, author = {Shepherd, KE and Oliver, LC and Kazemi, H}, title = {Diffuse malignant pleural mesothelioma in an urban hospital: clinical spectrum and trend in incidence over time.}, journal = {American journal of industrial medicine}, volume = {16}, number = {4}, pages = {373-383}, doi = {10.1002/ajim.4700160405}, pmid = {2610210}, issn = {0271-3586}, support = {1 ROIES 03301/ES/NIEHS NIH HHS/United States ; }, mesh = {Asbestos/*adverse effects ; Environmental Exposure ; Female ; Humans ; Male ; Massachusetts ; Mesothelioma/diagnosis/*epidemiology/etiology ; Pleural Neoplasms/diagnosis/*epidemiology/etiology ; Retrospective Studies ; }, abstract = {This retrospective analysis reviews the clinical experience of a major urban referral hospital with diffuse malignant pleural mesothelioma during the 14-year period from 1973 through 1986. Seventy-five cases of definite or equivocal mesothelioma were identified. There were four cases of primary malignant peritoneal mesothelioma, seven cases of benign fibrous mesothelioma, and 64 cases of diffuse malignant pleural mesothelioma. In 43 cases (67%) of diffuse malignant pleural mesothelioma, there was historic evidence of asbestos exposure. In 21 cases (33%), there was no known history of asbestos exposure. An increase in annual incidence of diffuse malignant pleural mesothelioma was observed over the study period, from three cases in 1973 to ten cases in 1986. Despite greater awareness of this disease, the diagnosis remains a difficult one to establish given the nonspecific symptoms, signs and radiographic appearance, variable histologic appearance, and poor diagnostic sensitivity and specificity of thoracentesis and closed pleural biopsy. Thoracotomy, thoracoscopy, and CT-guided needle biopsies gave higher yields and are the diagnostic measures of choice when diffuse malignant pleural mesothelioma is suspected.}, } @article {pmid2595107, year = {1989}, author = {Zerva, LV and Constantopoulos, SH and Moutsopoulos, HM}, title = {Humoral immunity alterations after environmental asbestos exposure.}, journal = {Respiration; international review of thoracic diseases}, volume = {55}, number = {4}, pages = {237-241}, doi = {10.1159/000195740}, pmid = {2595107}, issn = {0025-7931}, mesh = {Adult ; Aged ; Antibodies/*analysis ; Antibodies, Antinuclear/analysis ; Antibody Formation ; Asbestos/*adverse effects ; Asbestosis/etiology/*immunology ; C-Reactive Protein/analysis ; Complement System Proteins/analysis ; Environmental Pollutants/*adverse effects ; Female ; Greece ; Humans ; Immunoglobulins/analysis ; Male ; Middle Aged ; }, abstract = {The inhabitants of Metsovo in northwestern Greece have been environmentally exposed to asbestos from childhood because they had been using a tremolite-containing material for whitewash, without knowing its consistency. As a result, they have a very high incidence of calcified pleural plaques and malignant pleural mesothelioma but no pulmonary fibrosis. In the present study we examined certain aspects of the humoral immunity in the serum of 109 individuals: levels of immunoglobulins, C-reactive protein and complement components, as well as the presence of antinuclear antibodies, rheumatoid factor, antibodies to extractable nuclear antigens, to ds-DNA and to cardiolipin. Our results show that, compared to controls, those exposed to asbestos have increased IgG and C3 levels. Those with pleural plaques have, in addition, increased IgA levels and an increased incidence of antinuclear antibodies. The results of the study suggest that nonoccupational asbestos exposure affects humoral immunity. The presence of pleural plaques accentuates this effect.}, } @article {pmid2547573, year = {1989}, author = {Vasil'eva, LA and Pylev, LN and Vezentsev, AI and Smolikov, AA}, title = {[Carcinogenic activity of synthetic chrysotile asbestos with various fiber sizes and chemical composition].}, journal = {Eksperimental'naia onkologiia}, volume = {11}, number = {4}, pages = {26-29}, pmid = {2547573}, issn = {0204-3564}, mesh = {Animals ; Asbestos/*toxicity ; Asbestos, Serpentine ; Carcinogens/*toxicity ; Chemical Phenomena ; Chemistry ; Female ; Male ; Neoplasms, Experimental/chemically induced/epidemiology ; Particle Size ; Rats ; Risk Factors ; Structure-Activity Relationship ; }, abstract = {Synthetic Mg-chrysotiles (analogous to natural ones by chemical composition) with fine short, thick short and fine long fibres under intrapleural injections (20 mg thrice) induced mesotheliomas in noninbred rats in 3.3, 0 and 12% of rats, respectively. Ni- and Co-chrysotiles with fine and short fibres caused such tumours in 7.6 and 30.2%, Co-chrysotile with plate-like fibres induced tumours in 26.8%. The role of chemical structure and particle sizes have been discussed.}, } @article {pmid2545618, year = {1989}, author = {Berry, G and Rogers, AJ and Pooley, FD}, title = {Mesotheliomas--asbestos exposure and lung burden.}, journal = {IARC scientific publications}, volume = {}, number = {90}, pages = {486-496}, pmid = {2545618}, issn = {0300-5038}, mesh = {Air Pollutants/adverse effects/*analysis ; Asbestos/adverse effects/*analysis ; Asbestos, Amosite ; Asbestos, Amphibole ; Asbestos, Crocidolite ; Australia ; Humans ; Lung/*analysis ; Mesothelioma/*etiology ; North America ; Silicon Dioxide/analysis ; Tissue Distribution ; United Kingdom ; }, abstract = {The assessment of asbestos fibres in the lungs at post mortem in groups of mesotheliomas, groups occupationally exposed to asbestos, and controls has shown that all these groups contain significant levels of asbestos as a lung burden. The amounts in each group are dependent on the degree of past exposure, being highest in those cases with a known or extrapolated occupational exposure, less in those cases with recorded neighbourhood or environmental exposure, and less again in those cases with no evidence of exposure to asbestos and in controls. Relative risk estimates and the use of models developed for occupational situations do not provide good estimates of the relevance of environmental fibres in producing mesotheliomas in the general population. This may be the result of differences between the groups in their time periods of exposure and long-term elimination of asbestos from the lungs. The number of mesotheliomas that might be due to low-level environmental exposure to asbestos cannot be determined from lung contents alone, but an assessment based on detailed occupational histories from the Australian Mesothelioma Surveillance Program show that the problem is not one of great importance when compared with other public health issues.}, } @article {pmid2545617, year = {1989}, author = {Wagner, JC and Newhouse, ML and Corrin, B and Rossiter, CE and Griffiths, DM}, title = {Correlation between lung fibre content and disease in East London asbestos factory workers.}, journal = {IARC scientific publications}, volume = {}, number = {90}, pages = {444-448}, pmid = {2545617}, issn = {0300-5038}, mesh = {Aluminum Silicates/analysis ; Asbestos/adverse effects/*analysis ; Asbestos, Amosite ; Asbestos, Crocidolite ; Asbestos, Serpentine ; Asbestosis/pathology ; Female ; Humans ; London ; Lung/*analysis ; Lung Diseases/*etiology/mortality ; Lung Neoplasms/analysis ; Male ; Mesothelioma/analysis ; Middle Aged ; Occupational Diseases/*etiology ; Pleural Neoplasms/analysis ; }, abstract = {The lungs from 36 former workers at an East London asbestos factory dying of asbestos-related disease were compared with lung tissue from 56 matched control patients operated on in East London for carcinoma of the lung. The severity of asbestosis and the presence of pulmonary carcinoma or mesothelioma of the pleura or peritoneum were correlated with an asbestos exposure index and with the type and amount of mineral fibre of the lungs. Asbestosis was associated with far heavier fibre burdens than mesothelioma. Moderate or severe asbestosis was more common among those with carcinoma of the lung than in those with mesothelial tumours. Crocidolite and amosite asbestos were strongly associated with asbestosis, carcinoma of the lung and mesothelial tumours, whereas no such correlation was evident with chrysotile or mullite. It is suggested that greater emphasis should be placed on the biological differences between amphibole and serpentine asbestos fibre.}, } @article {pmid2545616, year = {1989}, author = {Morinaga, K and Kohyama, N and Yokoyama, K and Yasui, Y and Hara, I and Sasaki, M and Suzuki, Y and Sera, Y}, title = {Asbestos fibre content of lungs with mesotheliomas in Osaka, Japan: a preliminary report.}, journal = {IARC scientific publications}, volume = {}, number = {90}, pages = {438-443}, pmid = {2545616}, issn = {0300-5038}, mesh = {Asbestos/*analysis ; Asbestos, Amphibole ; Asbestos, Serpentine ; Female ; Heart Neoplasms/analysis ; Humans ; Lung/*analysis ; Male ; Mesothelioma/*analysis ; Mining ; Occupational Diseases/metabolism ; Particle Size ; Peritoneal Neoplasms/analysis ; Pleural Neoplasms/analysis ; Silicon Dioxide/analysis ; }, abstract = {That crocidolite and amosite are both associated with the development of mesothelioma is now well established, but earlier studies have failed to find an excess of chrysotile in lungs with mesotheliomas as compared with the amounts in lungs of unaffected controls. In an attempt to clarify the importance of fibre type in tissue, an examination of a series of mesotheliomas is being undertaken in Osaka, Japan. A total of 23 mesotheliomas and 5 rejected cases reviewed by the Osaka Mesothelioma Panel were examined for the types of asbestos and semiquantitative fibre content by means of a transmission electron microscope equipped with energy-dispersive X-ray analyser. Asbestos fibres were detected in 19 of the 23 mesotheliomas (21 pleura, 1 pericardium, 1 peritoneum; 19 males, 4 females). Amphibole fibres were found in 13 cases. Five pleural and one peritoneal mesothelioma were found to have only chrysotile fibres. One female pleural mesothelioma with neighbourhood exposure had short chrysotile fibres. Among the 5 rejected cases, only one case with occupational exposure had both chrysotile and amosite fibres. A group of 17 controls were also examined and asbestos fibres were found in 5. Our data, while not definitive, suggest that mesotheliomas can be induced in humans, not only by crocidolite and amosite, but also by chrysotile, though possibly to a lesser extent.}, } @article {pmid2545615, year = {1989}, author = {McConnochie, K and Simonato, L and Mavrides, P and Christofides, P and Mitha, R and Griffiths, DM and Wagner, JC}, title = {Mesothelioma in Cyprus.}, journal = {IARC scientific publications}, volume = {}, number = {90}, pages = {411-419}, pmid = {2545615}, issn = {0300-5038}, mesh = {Air Pollutants/*adverse effects/analysis ; Animals ; Asbestos/*adverse effects/analysis ; *Asbestos, Amphibole ; Asbestos, Crocidolite ; Asbestos, Serpentine ; Cyprus ; Humans ; Lung/analysis ; Mesothelioma/diagnostic imaging/epidemiology/*etiology ; Mining ; Pleural Neoplasms/diagnostic imaging/epidemiology/*etiology ; Radiography ; Sheep ; Silicic Acid/analysis ; }, abstract = {For many years, the main source of asbestos in Cyprus was thought to be the chrysotile mine in the central mountains. When a woman, who had no connection with the mine, developed mesothelioma, it was surprising to discover tremolite asbestos bodies within her lung. However, further studies have shown that tremolite occurs as a contaminant within the chrysotile ore body. In this study we have shown that both chrysotile and tremolite can be found in domestic and environmental samples throughout the mountain region; in particular, numerous fine fibres of both materials are present in stucco. Preliminary radiological studies have shown pleural disease in the village population and 5 out of 13 known cases of mesothelioma have arisen in persons unconnected with the mine. This suggests an environmental contribution to asbestos-related disease on the island.}, } @article {pmid2545611, year = {1989}, author = {Churg, A and Wright, JL}, title = {Fibre content of lung in amphibole- and chrysotile-induced mesothelioma: implications for environmental exposure.}, journal = {IARC scientific publications}, volume = {}, number = {90}, pages = {314-318}, pmid = {2545611}, issn = {0300-5038}, mesh = {Aged ; Asbestos/adverse effects/*analysis ; Asbestos, Amphibole ; Asbestos, Serpentine ; Asbestosis/pathology ; Humans ; Lung/*analysis ; Lung Neoplasms/*etiology/pathology ; Mesothelioma/*etiology/pathology ; Middle Aged ; Occupational Diseases/etiology/pathology ; Silicon Dioxide/adverse effects/*analysis ; }, abstract = {Using 9 pairs of exposure-period-matched shipyard and insulation workers (amphibole exposure) and chrysotile-industry workers (chrysotile exposure) with mesothelioma, and an additional 9 pairs of workers with asbestosis, we found that the chrysotile workers with mesothelioma had 400 times the median lung fibre burden of the shipyard and insulation workers with mesothelioma. Mesothelioma in the chrysotile workers was associated with a 3 times greater median fibre burden than asbestosis, whereas in the shipyard and insulation workers mesothelioma was associated with only 1/35 the median amphibole burden seen in cases of asbestosis. In the chrysotile workers, the tremolite:chrysotile ratio and the mean fibre sizes were the same for both mesothelioma and asbestosis cases. These data suggest that total fibre load is crucial to the induction of mesothelioma by chrysotile, and that this phenomenon requires, on average, as high a fibre burden as induction of asbestosis by chrysotile. By contrast, for amphibole exposure, mesothelioma appears at a much lower fibre burden than asbestosis. The fibre types appear to differ by at least two orders of magnitude in their potential for inducing mesothelioma. Estimates of risk from environmental exposure must take these differences into account.}, } @article {pmid2545610, year = {1989}, author = {Gibbs, AR and Jones, JS and Pooley, FD and Griffiths, DM and Wagner, JC}, title = {Non-occupational malignant mesotheliomas.}, journal = {IARC scientific publications}, volume = {}, number = {90}, pages = {219-228}, pmid = {2545610}, issn = {0300-5038}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*analysis ; Asbestos, Amphibole ; Asbestos, Serpentine ; Female ; Humans ; Lung/*analysis ; Male ; Mesothelioma/*analysis/etiology/ultrastructure ; Middle Aged ; Pleural Neoplasms/*analysis/etiology/ultrastructure ; Silicon Dioxide/analysis ; }, abstract = {The mineral content of the lungs from 84 cases of malignant pleural mesothelioma was estimated by electron microscopy and energy-dispersive X-ray analysis. These cases were chosen because the history of asbestos exposure was absent, indirect or ill-defined. The occupational exposures were classified according to the method of Zielhuis, and the results indicated that this classification is unnecessarily complicated. The chrysotile counts in the lungs from these mesothelioma cases were similar to those in controls and in a previous series of mesotheliomas in which the majority had had direct exposure to asbestos. Amphibole counts were intermediate between those in controls and in the previous series of mesotheliomas with direct asbestos exposure. These findings confirm those of previous studies indicating that amphiboles are more important than chrysotile in the causation of malignant mesothelioma. The results confirm that some mesotheliomas develop in the absence of asbestos exposure.}, } @article {pmid2545606, year = {1989}, author = {Renier, A and Fleury, J and Monchaux, G and Nebut, M and Bignon, J and Jaurand, MC}, title = {Toxicity of an attapulgite sample studied in vivo and in vitro.}, journal = {IARC scientific publications}, volume = {}, number = {90}, pages = {180-184}, pmid = {2545606}, issn = {0300-5038}, mesh = {Animals ; Asbestos/toxicity ; Asbestos, Serpentine ; *Carcinogens ; Cells, Cultured ; DNA Replication/drug effects ; Magnesium/*toxicity ; *Magnesium Compounds ; Male ; Mesothelioma/etiology ; Particle Size ; Pleura/drug effects ; Pleural Neoplasms/etiology ; Rats ; Rats, Inbred Strains ; Silicon/*toxicity ; *Silicon Compounds ; }, abstract = {Conflicting data are found in the literature concerning the carcinogenic potency of attapulgite. We tested the carcinogenic potency of French attapulgite in rats, and compared it with 2 chrysotile samples: Rhodesian UICC (Ch A) and short Canadian fibres (Ch C). The mean length of the fibres was 0.77 micron (attapulgite), 3.21 microns (Ch A) and 1.25 microns (Ch C). The mean diameter was 0.06 micron in the 3 samples. The particles (20 mg) in saline were inoculated into the pleural cavity of Sprague-Dawley rats allowed to survive for their full lifespan. The incidence rates of mesothelioma were: 0% (saline controls), 0% (attapulgite), 19% (ChC) and 48% (Ch A). In vitro studies were carried out using cultures of rat pleural mesothelial cells (RPMC). Attapulgite and Ch C did not modify cell growth except at high doses of 10 micrograms/cm2. Unscheduled DNA synthesis (UDS) was detected using [3H]thymidine incorporation in confluent RPMC (GoG1 arrested) and a scintillation method. UDS was stimulated with either Ch A or Ch C at doses ranging from 2 to 10 micrograms/cm2. In contrast, attapulgite did not significantly enhance [3H]thymidine incorporation at doses ranging from 2 to 20 micrograms/cm2. The results show that the attapulgite tested here had no carcinogenic potency. The in vivo and in vitro reactivity of the fibres used in this experiment might perhaps be related to the fibre size; however, other parameters may also be important.}, } @article {pmid2545605, year = {1989}, author = {Palekar, LD and Eyre, JF and Coffin, DL}, title = {Transplantation and chromosomal analysis of cell lines derived from mesotheliomas induced in rats with erionite and UICC chrysotile asbestos.}, journal = {IARC scientific publications}, volume = {}, number = {90}, pages = {167-172}, pmid = {2545605}, issn = {0300-5038}, mesh = {Aluminum Silicates/*toxicity ; Animals ; Asbestos/*toxicity ; Asbestos, Serpentine ; Chromosome Aberrations/etiology ; Chromosome Disorders ; Karyotyping ; Male ; Mesothelioma/etiology/*genetics/pathology ; Neoplasm Transplantation ; Ploidies ; Rats ; Rats, Inbred F344 ; Tumor Cells, Cultured ; Zeolites ; }, abstract = {The histological lesions, chromosomal characteristics and transplantability of 6 erionite-induced and 7 UICC chrysotile-induced rat mesotheliomas are compared. The tumours were of 4 types: tubulopapillary, fibrosarcomatous, mixed fibrosarcomatous and tubulopapillary, and mixed fibrosarcomatous and chondrosarcomatous. Cell lines derived from these tumours displayed heterogeneous chromosome anomalies, but none were unique either to chrysotile or erionite treatment. Six of 7 erionite-induced and 4 of 6 UICC chrysotile-induced tumours had various anomalies of chromosome No. 1. When 7 cell lines were transplanted into syngeneic rats, all produced tumours that were pathologically similar to the original tumour, regardless of the route of injection. Cytogenetically, the cell lines derived from tumours after intrapleural transplantation resembled the injected cell line. The cytogenetic analysis of the cell lines derived from the tumours after subcutaneous transplantation is in progress. The induction period for transplanted tumours was 28-80 days.}, } @article {pmid2545604, year = {1989}, author = {Monchaux, G and Chameaud, J and Morlier, JP and Janson, X and Morin, M and Bignon, J}, title = {Translocation of subcutaneously injected chrysotile fibres: potential cocarcinogenic effect on lung cancer induced in rats by inhalation of radon and its daughters.}, journal = {IARC scientific publications}, volume = {}, number = {90}, pages = {161-166}, pmid = {2545604}, issn = {0300-5038}, mesh = {Administration, Inhalation ; Animals ; Asbestos/administration & dosage/metabolism/*toxicity ; Asbestos, Serpentine ; *Cocarcinogenesis ; Injections, Subcutaneous ; Lung/metabolism ; Lung Neoplasms/*etiology ; Lymph Nodes/metabolism ; Male ; Neoplasms, Radiation-Induced/etiology ; Particle Size ; Radon/*toxicity ; Rats ; Rats, Inbred Strains ; Tissue Distribution ; }, abstract = {Exposure to radon 222 and its daughters has been shown to induce lung cancer in rats. The cocarcinogenic effect of intrapleurally injected mineral fibres in rats which have previously inhaled radon has also been established. The aim of this work was to establish whether a similar process could be induced at a distance from the lungs by subcutaneous injection of chrysotile fibres. Three groups of animals were used: (1) 109 rats which inhaled radon only (dose: 1600 working-level months (WLM]; (2) 109 rats given a subcutaneous injection in the sacrococcygeal region of 20 mg of chrysotile fibres after inhalation of the same dose of radon; and (3) 105 rats injected with fibres only. No mesotheliomas occurred in any of the 3 groups. The incidence of lung cancer was 55% in group 2, 49% in group 1 and 1% in group 3. Statistical analysis using Pike's model showed that the carcinogenic insult was slightly higher in group 2 than in group 1. Electron microscopy analysis of fibre translocation from the injection site showed that less than 1% of injected fibres migrated to the regional lymph-nodes and only about 0.01% to the lungs. After injection, the mean length of the fibres recovered in lung parenchyma increased with time, suggesting that short fibres are cleared by pulmonary macrophages whereas long fibres are trapped in the alveolar walls. Although the high tumour incidence observed in group 1 might have masked the cocarcinogenic effect induced by the fibres, it is possible that this effect can occur only at short distances.(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid2545601, year = {1989}, author = {Pezerat, H and Zalma, R and Guignard, J and Jaurand, MC}, title = {Production of oxygen radicals by the reduction of oxygen arising from the surface activity of mineral fibres.}, journal = {IARC scientific publications}, volume = {}, number = {90}, pages = {100-111}, pmid = {2545601}, issn = {0300-5038}, mesh = {*Asbestos ; Asbestos, Serpentine ; Free Radicals ; *Minerals ; Oxidation-Reduction ; *Oxygen ; Surface Properties ; }, abstract = {According to certain hypotheses, the production of oxygen radicals within the biological medium (the phenomenon of oxidative stress) may play an important role in fibrosis and in certain steps of carcinogenesis. The mineral fibres of various materials are capable of participating in this phenomenon, owing to the reducing nature of their surface activity, so that OH. radicals can be produced from oxygen in 3 steps. The surface activity of inorganic materials which are insoluble or only very slightly soluble is due to the presence of electron donor active sites, generally linked to Fe2+ ions found in the neighbourhood of the surface. In biological systems, these sites may emerge on the surface as a result of the partial dissolution of the particle, the action of a biological reducing agent, the phenomenon of deposition on the surfaces or cation exchange. We have explored the reducing properties of the surfaces of a certain number of mineral fibres, in aqueous buffer medium, by electron paramagnetic resonance (EPR) measurement of the adduct with the radical-trapping agent 5,5'-dimethyl-l-pyrrolidine-N-oxide (DMPO), produced from the radicals initially formed (OH. or R.). We have found certain fibres to be highly effective in producing radicals from dissolved oxygen (Canadian chrysotile, nemalite, freshly ground amphiboles) while others have little effect. The reducing activity of certain fibres may be markedly increased by prior treatment in the presence of a ferrous salt (as in the case of erionite) or by the addition of glutathione to the reaction medium (as in the case of UICC crocidolite). It is suggested that the carcinogenic activity of certain inorganic materials at the pulmonary level is the result of their surface reducing properties. These reducing properties may either be present at the time of inhalation or acquired in the biological medium. This hypothesis is not in conflict with the observation of the role of the dimensional characteristics of fibres in mesothelioma.}, } @article {pmid2545547, year = {1989}, author = {Nikitina, OV and Kogan, FM and Vanchugova, NN and Frash, VN}, title = {[Comparative carcinogenic properties of basalt fiber and chrysotile-asbestos].}, journal = {Gigiena truda i professional'nye zabolevaniia}, volume = {}, number = {4}, pages = {7-11}, pmid = {2545547}, issn = {0016-9919}, mesh = {Animals ; Asbestos/*adverse effects ; Asbestos, Serpentine ; Mesothelioma/*etiology ; Minerals/*adverse effects ; Peritoneal Neoplasms/*etiology ; Rats ; Risk Factors ; *Silicates ; Silicon Dioxide/*adverse effects ; }, abstract = {In order to eliminate asbestos adverse effect on workers' health it was necessary to use mineral rayon, primarily basalt fibre, instead of asbestos. During a chronic experiment on animals the oncogenicity of 2 kinds of basalt fibre was studied compared to chrysotile asbestos. The dust dose of 25 mg was twice administered by intraperitonial route. All types of dust induced the onset of intraperitonial mesotheliomas but neoplasm rates were significantly lower in the groups exposed to basalt fibre. There was no credible data on the differences between the groups exposed to various types of basalt fibre. Since the latter produced some oncogenic effect, it was necessary to develop a complex of antidust measures, fully corresponding to the measures adopted for carcinogenic dusts.}, } @article {pmid2544391, year = {1989}, author = {Vasil'eva, LA and Pylev, LN and Kiianenko, VV and Nikolaĭshvili, AA}, title = {[Carcinogenic properties of silicon carbide whiskers].}, journal = {Eksperimental'naia onkologiia}, volume = {11}, number = {2}, pages = {13-15}, pmid = {2544391}, issn = {0204-3564}, mesh = {Animals ; Asbestos/toxicity ; Asbestos, Serpentine ; Carbon/*toxicity ; *Carbon Compounds, Inorganic ; Crystallization ; Female ; Male ; Neoplasms, Experimental/*chemically induced/epidemiology/pathology ; Particle Size ; Rats ; Risk Factors ; Silicon/*toxicity ; *Silicon Compounds ; }, abstract = {In experiments with intrapleural injections of silicon carbide whiskers (20 mg X 3, with one month interval) to random-inbred rats their carcinogenic activity close to that of chrysotile B UICC has been established. The pleural mesotheliomas were induced in 47.7 and 34.1% of rats, respectively.}, } @article {pmid2543218, year = {1989}, author = {Higgins, I}, title = {Relative risk of mesothelioma among railroad machinists exposed to chrysotile.}, journal = {American journal of industrial medicine}, volume = {15}, number = {4}, pages = {483-486}, doi = {10.1002/ajim.4700150412}, pmid = {2543218}, issn = {0271-3586}, mesh = {Asbestos/*adverse effects ; Asbestos, Serpentine ; Cohort Studies ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; *Railroads ; Risk Factors ; }, } @article {pmid2539874, year = {1989}, author = {Fleury-Feith, J and Nebut, M and Saint-Etienne, L and Laurent, P and Pinchon, MC and Kheuang, L and Renier, A and Jaurand, MC}, title = {Occurrence and morphology of tumors induced in nude mice transplanted with chrysotile-transformed rat pleural mesothelial cells.}, journal = {Biology of the cell}, volume = {65}, number = {1}, pages = {45-50}, pmid = {2539874}, issn = {0248-4900}, mesh = {Animals ; *Asbestos ; Asbestos, Serpentine ; Cell Transformation, Neoplastic ; Cells, Cultured ; Mesothelioma/*etiology/pathology/ultrastructure ; Mice ; Mice, Nude ; Microscopy, Electron ; Neoplasm Transplantation ; Pleura/*pathology ; Pleural Neoplasms/*etiology/pathology/ultrastructure ; Rats ; Transplantation, Heterologous ; }, abstract = {Rat pleural mesothelial cells treated in vitro with chrysotile fibers have been successfully transplanted into nude mice. Three cultures (1 untreated, 2 treated) were injected at passage 75; a fourth culture was obtained from a mesothelioma induced in rat by chrysotile fibers. Overall, tumors grew in each series, but the delay between cell injection and tumor formation was 22 wk with untreated cells whereas only 1 or 2 wk were needed with treated cells, and 1 wk with cells from in vivo-induced mesothelioma. Pathological study by light and electron microscopy of tumors is reported here and showed the mesothelial nature of the cells. Comparison between the ultrastructure of the injected cells and tumor cells indicated that the morphology of injected cells was retained in tumors even if the delay in tumor formation was long. These results suggest that this model is useful for investigating mesothelial cell transformation resulting from in vitro or in vivo exposure to certain carcinogens.}, } @article {pmid2539016, year = {1989}, author = {Ohlson, CG}, title = {Is chrysotile a significant risk factor for mesothelioma?.}, journal = {American journal of industrial medicine}, volume = {15}, number = {3}, pages = {351-356}, doi = {10.1002/ajim.4700150311}, pmid = {2539016}, issn = {0271-3586}, mesh = {Asbestos/*adverse effects ; Asbestos, Serpentine ; Humans ; Lung Neoplasms/*etiology ; Male ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; *Railroads ; Risk Factors ; }, } @article {pmid2531545, year = {1989}, author = {Finkelstein, MM}, title = {Analysis of mortality patterns and workers' compensation awards among asbestos insulation workers in Ontario.}, journal = {American journal of industrial medicine}, volume = {16}, number = {5}, pages = {523-528}, doi = {10.1002/ajim.4700160505}, pmid = {2531545}, issn = {0271-3586}, mesh = {Asbestos/*adverse effects ; Asbestosis/etiology/*mortality ; Humans ; Insurance Claim Review ; Male ; Neoplasms/etiology/*mortality ; Ontario ; *Workers' Compensation ; }, abstract = {Mortality and workers' compensation patterns were studied among 1,064 Ontario asbestos insulation workers. A proportional mortality analysis of 153 asbestos worker deaths found increased mortality from malignant diseases (65 deaths observed; 35.1 expected), cancers of the lungs and pleura (32 deaths observed; 11.5 expected), peritoneal mesothelioma (4 deaths), and respiratory diseases (14 deaths observed; 7.9 expected). Despite the publicity given to asbestos-associated diseases, dependents of many men potentially eligible for workers compensation awards have not received pensions because claims were not filed. These findings suggest that much occupationally related disease is not being recognized in Ontario.}, } @article {pmid2465565, year = {1989}, author = {Lange, S}, title = {[Radiologic diagnosis and therapy of pleural mesothelioma].}, journal = {Rontgen-Blatter; Zeitschrift fur Rontgen-Technik und medizinisch-wissenschaftliche Photographie}, volume = {42}, number = {1}, pages = {28-30}, pmid = {2465565}, issn = {0300-8592}, mesh = {Asbestosis/epidemiology ; Germany, West ; Humans ; *Mesothelioma/diagnostic imaging/epidemiology/radiotherapy ; Palliative Care ; *Pleural Neoplasms/diagnostic imaging/epidemiology/radiotherapy ; Radiography ; }, abstract = {In Germany pleural mesothelioma occurs annually in 100-200 patients who had usually been working in the asbestos industry. In 100 mesotheliomas, evaluated radiologically, 61 presented pleural effusions and 82 a pleural tumour. This may result in retracting the hemithorax. Radiotherapy has a palliative goal. Applying 40 Gy may reduce pain and may inhibit fluid production. The irradiated volume should, if possible, spare lung tissue, which necessitates careful treatment planning.}, } @article {pmid3273138, year = {1988}, author = {Albin, M and Johansson, L and Pooley, FD and Jakobsson, K and Attewell, R and Welinder, H}, title = {Mineral fibres, fibrosis, and asbestos bodies in lung tissue from deceased asbestos-cement workers.}, journal = {Arhiv za higijenu rada i toksikologiju}, volume = {39}, number = {4}, pages = {447-453}, pmid = {3273138}, issn = {0004-1254}, mesh = {Asbestos/adverse effects/analysis ; Asbestosis/*pathology ; Humans ; Lung/analysis/*pathology ; Lung Neoplasms/analysis/etiology ; Mesothelioma/analysis/etiology ; Minerals/*analysis ; }, } @article {pmid3273136, year = {1988}, author = {Järvholm, B and Sandén, A}, title = {Asbestos-associated diseases in Swedish shipyard workers.}, journal = {Arhiv za higijenu rada i toksikologiju}, volume = {39}, number = {4}, pages = {437-440}, pmid = {3273136}, issn = {0004-1254}, mesh = {Asbestos/*adverse effects ; Asbestosis/epidemiology/*etiology ; Humans ; Lung Neoplasms/epidemiology/etiology ; Male ; Mesothelioma/epidemiology/etiology ; Pleural Diseases/epidemiology/etiology ; *Ships ; Sweden/epidemiology ; }, } @article {pmid3273134, year = {1988}, author = {Järvholm, B}, title = {Asbestos-associated diseases in Sweden--a general view.}, journal = {Arhiv za higijenu rada i toksikologiju}, volume = {39}, number = {4}, pages = {429-432}, pmid = {3273134}, issn = {0004-1254}, mesh = {Asbestos/*adverse effects ; Asbestosis/*epidemiology ; Environmental Monitoring ; Epidemiological Monitoring ; Humans ; Mesothelioma/epidemiology/etiology ; Pleural Diseases/epidemiology/etiology ; Pleural Neoplasms/epidemiology/etiology ; Sex Factors ; Sweden/epidemiology ; }, } @article {pmid3243527, year = {1988}, author = {Yang, GH and Tan, YS and Liu, XZ and Luo, SQ}, title = {[Ultrastructural and immunohistochemical study of mesothelioma induced by asbestos in rat].}, journal = {Hua xi yi ke da xue xue bao = Journal of West China University of Medical Sciences = Huaxi yike daxue xuebao}, volume = {19}, number = {4}, pages = {337-341}, pmid = {3243527}, issn = {0257-7712}, mesh = {Animals ; Asbestos ; Immunohistochemistry ; Mesothelioma/etiology/*ultrastructure ; Microscopy, Electron ; Pleural Neoplasms/*etiology/*ultrastructure ; Rats ; Rats, Inbred Strains ; }, } @article {pmid3219308, year = {1988}, author = {Bariş, YI and Artvinli, M and Sahin, AA and Bilir, N and Kalyoncu, F and Sebastien, P}, title = {Non-occupational asbestos related chest diseases in a small Anatolian village.}, journal = {British journal of industrial medicine}, volume = {45}, number = {12}, pages = {841-842}, pmid = {3219308}, issn = {0007-1072}, mesh = {Adult ; Asbestos/*adverse effects ; *Asbestos, Amphibole ; Asbestosis/etiology ; Environmental Exposure ; Female ; Hodgkin Disease/etiology ; Humans ; Male ; Mesothelioma/*etiology ; Middle Aged ; Pleural Neoplasms/*etiology ; Rural Population ; Silicic Acid/adverse effects ; Stomach Neoplasms/etiology ; Turkey ; }, } @article {pmid3059081, year = {1988}, author = {Pisani, RJ and Colby, TV and Williams, DE}, title = {Malignant mesothelioma of the pleura.}, journal = {Mayo Clinic proceedings}, volume = {63}, number = {12}, pages = {1234-1244}, doi = {10.1016/s0025-6196(12)65411-1}, pmid = {3059081}, issn = {0025-6196}, mesh = {Adenocarcinoma/pathology ; Combined Modality Therapy ; Diagnosis, Differential ; Humans ; Mesothelioma/*diagnosis/pathology/therapy ; Pleural Neoplasms/*diagnosis/pathology/therapy ; Prognosis ; }, abstract = {Malignant mesothelioma of the pleura most commonly occurs in persons with a heavy occupational exposure to asbestos. Some patients, however, have no such history of exposure. Clinical features include initial complaints of nonpleuritic chest pain and dyspnea. The most frequent roentgenographic finding is a unilateral pleural effusion. Thrombocytosis and elevated erythrocyte sedimentation rates are common. Pleural effusions are typically exudates, are often hemorrhagic, and are usually insufficient for diagnosing mesothelioma based on cytology alone. Even pleural biopsy may not produce enough tissue to enable the pathologist to make a firm diagnosis. Thoracotomy and open biopsy will confirm the diagnosis in most cases. Pathologic distinction from metastatic adenocarcinoma may be difficult even after the use of special stains and electron microscopy. Clinical deterioration is primarily attributable to local spread of tumor. Several factors seem to predict prolonged survival: (1) epithelial histologic subtype, (2) performance score, (3) age of the patient at the time of diagnosis, and (4) absence of chest pain. Surgical treatment, chemotherapy, and irradiation, alone or in combination, have been used for malignant mesothelioma. Except for the palliative effect of irradiation, most treatment protocols have not altered the dismal median survival of approximately 11 months seen in untreated patients with malignant mesothelioma.}, } @article {pmid2851315, year = {1988}, author = {Baris, YI and Bilir, N and Artvinli, M and Sahin, AA and Kalyoncu, F and Sebastien, P}, title = {An epidemiological study in an Anatolian village environmentally exposed to tremolite asbestos.}, journal = {British journal of industrial medicine}, volume = {45}, number = {12}, pages = {838-840}, pmid = {2851315}, issn = {0007-1072}, mesh = {Adult ; Asbestos/*adverse effects ; *Asbestos, Amphibole ; Environmental Exposure ; Female ; Humans ; Lung Diseases/*epidemiology ; Male ; Mesothelioma/etiology ; Pleural Diseases/*epidemiology ; Pleural Neoplasms/etiology ; Rural Population ; Silicic Acid/*adverse effects ; Silicon Dioxide/*adverse effects ; Turkey ; }, } @article {pmid3206498, year = {1988}, author = {Solheim, O and Finnanger, AM and Stenwig, AE and Børmer, OP}, title = {[Treatment of diffuse malignant mesothelioma of the pleura].}, journal = {Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke}, volume = {108}, number = {33}, pages = {3091-3093}, pmid = {3206498}, issn = {0029-2001}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Female ; Humans ; Male ; Mesothelioma/*drug therapy/etiology/pathology ; Methotrexate/*administration & dosage ; Middle Aged ; Occupational Diseases/drug therapy ; Pleural Neoplasms/*drug therapy/etiology/pathology ; }, } @article {pmid3060730, year = {1988}, author = {Burdorf, A and Swuste, P and van der Maas, P}, title = {[Asbestos and health: from patient presentation to recognition of occupational diseases in The Netherlands].}, journal = {Nederlands tijdschrift voor geneeskunde}, volume = {132}, number = {47}, pages = {2162-2167}, pmid = {3060730}, issn = {0028-2162}, mesh = {Asbestosis/complications/*epidemiology ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Netherlands ; Occupational Diseases/diagnosis/epidemiology ; Registries ; }, } @article {pmid3180061, year = {1988}, author = {Libbus, BL and Craighead, JE}, title = {Chromosomal translocations with specific breakpoints in asbestos-induced rat mesotheliomas.}, journal = {Cancer research}, volume = {48}, number = {22}, pages = {6455-6461}, pmid = {3180061}, issn = {0008-5472}, support = {2R01-CA36993/CA/NCI NIH HHS/United States ; }, mesh = {Aneuploidy ; Animals ; Asbestos/*toxicity ; Female ; Gene Rearrangement ; Mesothelioma/etiology/*genetics ; Rats ; Rats, Inbred F344 ; *Translocation, Genetic ; X Chromosome ; }, abstract = {Cytogenetic analysis was conducted on cells of 15 rat mesotheliomas induced in rats by the i.p. inoculation of crocidolite or chrysotile asbestos. These tumor cells were diploid, triploid, or tetraploid. All tumor lines exhibited aneuploidy and marker chromosomes. Loss of at least one copy of the X chromosome was observed in each of the tumors analyzed, and loss of copies of chromosomes 8, 16, 20, or 18 characterized at least six of the tumors. Translocations were observed in 12 tumors, with six chromosome rearrangements present in at least two different tumors. However, the breakpoints were not always identical. On the other hand, translocations involving chromosomes 5, 10, and 13 exhibited repeated breakage at the same loci. Such specific and repetitive translocations may be involved in the process of asbestos-induced tumor development.}, } @article {pmid3054139, year = {1988}, author = {Scatarige, JC and Stitik, FP}, title = {Induction of thoracic malignancy in inorganic dust pneumoconiosis.}, journal = {Journal of thoracic imaging}, volume = {3}, number = {4}, pages = {67-79}, doi = {10.1097/00005382-198810000-00010}, pmid = {3054139}, issn = {0883-5993}, mesh = {Asbestos/adverse effects ; Asbestosis/complications/diagnostic imaging ; Humans ; Lung Neoplasms/diagnostic imaging/*etiology ; Mesothelioma/diagnostic imaging/*etiology ; Occupational Diseases/diagnostic imaging/*etiology ; Pneumoconiosis/*complications ; Radiography ; Silicosis/complications ; }, abstract = {Pulmonary carcinoma is now the leading cause of death due to cancer in men and women. Aside from cigarette smoking, occupational exposure to carcinogens is the most important cause of lung cancer, accounting for up to one third of all cases. The following article is a review of occupationally induced thoracic neoplasms with an emphasis on those related to the inhalation of inorganic dust. After introducing some basic terms, describing the research methods, and reviewing the process of carcinogenesis, current information on the relationship between exposure to asbestos, synthetic mineral fibers, silica, and other nonfibrous mineral dusts and the development of lung cancer and malignant mesothelioma of the pleura will be presented. The goal of this article is to provide the practicing radiologist with knowledge and insight into this difficult area.}, } @article {pmid2848570, year = {1988}, author = {Davis, JM and Jones, AD}, title = {Comparisons of the pathogenicity of long and short fibres of chrysotile asbestos in rats.}, journal = {British journal of experimental pathology}, volume = {69}, number = {5}, pages = {717-737}, pmid = {2848570}, issn = {0007-1021}, mesh = {Animals ; Asbestos/administration & dosage/analysis/*toxicity ; Asbestos, Serpentine ; Asbestosis/*etiology/pathology ; Dust ; Lung/analysis/pathology ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Pulmonary Fibrosis/pathology ; Rats ; Rats, Inbred Strains ; Time Factors ; }, abstract = {Long-term inhalation and intraperitoneal injection studies were undertaken with laboratory rats treated with a specially prepared short-fibre sample of Canadian chrysotile asbestos. This was compared, at an equal mass dose, to dust generated from the same chrysotile batch so as to contain the highest possible number of long fibres. The long-fibre cloud contained roughly five times more fibres greater than 5 micron in length as seen by phase contrast optical microscopy (PCOM). For increasing lengths, the ratio between the dust clouds increased progressively, reaching over 80: 1 for fibres greater than 30 microns in length. Rats treated with long-fibre chrysotile developed six times more advanced interstitial fibrosis (asbestosis) than animals treated with short-fibre chrysotile and three times more pulmonary tumours. At the end of the 12-month dusting period, three times more short chrysotile than long had been retained in the rat lung tissues. During the following 6 months, however, the short-fibre chrysotile was removed from the lungs much more rapidly than the long. Following intraperitoneal injection at a mass dose of 25mg of dust, both long and short chrysotile produced mesotheliomas in more than 90% of rats. At a dose level of 2.5mg of dust, the short-fibre chrysotile produced mesotheliomas in only one-third as many rats as the long-fibre dust which still produced mesotheliomas in more than 90% of animals injected. At a dose level of 0.25mg of dust, the short-fibre chrysotile produced no mesotheliomas while the long-fibre chrysotile still produced these tumours in 66% of rats. In the two highest doses, where short-fibre chrysotile produced mesotheliomas, the mean tumour induction period was significantly longer than for tumours produced by long chrysotile.}, } @article {pmid3411690, year = {1988}, author = {Prescott, S and Taylor, RE and Sclare, G and Busuttil, A}, title = {Malignant mesothelioma of the tunica vaginalis testis: a case report.}, journal = {The Journal of urology}, volume = {140}, number = {3}, pages = {623-624}, doi = {10.1016/s0022-5347(17)41741-1}, pmid = {3411690}, issn = {0022-5347}, mesh = {Humans ; Male ; *Mesothelioma/pathology/therapy ; Middle Aged ; *Testicular Neoplasms/pathology/therapy ; }, abstract = {We report a case of malignant mesothelioma of the testicular tunica vaginalis. A preceding hydrocele showed mesothelial hyperplasia of its lining. The tumor was treated surgically as well as with a combination of radiotherapy and chemotherapy but it progressed, resulting in death within 21 months from the diagnosis. The relationship of the tumor to mesothelial hyperplasia and to previous exposure to asbestos is discussed.}, } @article {pmid3409725, year = {1988}, author = {Kishimoto, T and Okada, K}, title = {The relationship between lung cancer and asbestos exposure.}, journal = {Chest}, volume = {94}, number = {3}, pages = {486-490}, doi = {10.1378/chest.94.3.486}, pmid = {3409725}, issn = {0012-3692}, mesh = {Asbestos/*adverse effects/analysis ; Female ; Humans ; Japan ; Lung/analysis/ultrastructure ; Lung Neoplasms/epidemiology/*etiology/pathology ; Male ; Occupational Diseases/epidemiology/etiology/pathology ; }, abstract = {This study supports the theory that asbestos exposure may be implicated in a recent upsurge of terminal lung cancer cases in Kure, Japan. The number of asbestos bodies found in the lung during autopsy of 158 subjects from 1984 to 1986 suggests that 70.4 percent of the 51 diagnosed lung cancer cases could be attributed to asbestos exposure. Of the 107 subjects in whom death was not caused by cancer, 38.4 percent had significant asbestos exposure. Types of asbestos bodies found in diagnosed lung cancer cases were analyzed using scanning electron microscopy and x-ray analyzer. Chrysotile was the most widely found component, but amphiboles such as crocidolite and amosite also were detected. Residents of Kure had high exposure to the inhalation of asbestos bodies, possibly related to the upsurge in lung cancer deaths. In our earlier report, asbestos exposure was implicated in the increased incidence of malignant mesothelioma in Kure, an active Japanese ship-building port since the 1920s. Our current findings indicate that asbestos exposure may be a pathogenic factor in lung cancer in world seaports where asbestos exposure has been prevalent.}, } @article {pmid3228908, year = {1988}, author = {Zhang, P}, title = {[Pathological investigation of asbestosis complicated by mesothelioma: report of 4 cases].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {17}, number = {3}, pages = {182-184}, pmid = {3228908}, issn = {0529-5807}, mesh = {Aged ; Asbestos/analysis ; Asbestosis/complications/*pathology ; Female ; Humans ; Male ; Mesothelioma/etiology/*pathology ; Middle Aged ; Pleura/analysis ; Pleural Neoplasms/etiology/*pathology ; }, } @article {pmid3179241, year = {1988}, author = {Järvholm, B and Brisman, J}, title = {Asbestos associated tumours in car mechanics.}, journal = {British journal of industrial medicine}, volume = {45}, number = {9}, pages = {645-646}, doi = {10.1136/oem.45.9.645}, pmid = {3179241}, issn = {0007-1072}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; *Automobiles ; Humans ; Lung Neoplasms/epidemiology/*etiology ; Male ; Mesothelioma/epidemiology/*etiology ; Middle Aged ; Occupational Diseases/epidemiology/*etiology ; }, } @article {pmid2846033, year = {1988}, author = {McDonald, JC and McDonald, AD and Sébastien, P and Moy, K}, title = {Health of vermiculite miners exposed to trace amounts of fibrous tremolite.}, journal = {British journal of industrial medicine}, volume = {45}, number = {9}, pages = {630-634}, pmid = {2846033}, issn = {0007-1072}, mesh = {Aluminum Silicates/*adverse effects ; *Asbestos, Amphibole ; Canada ; Cohort Studies ; Humans ; Lung Neoplasms/epidemiology/etiology/mortality ; Mesothelioma/epidemiology/mortality ; *Mining ; Occupational Diseases/*epidemiology/etiology/mortality ; Pulmonary Fibrosis/epidemiology/etiology/mortality ; Silicic Acid/*adverse effects ; Silicon Dioxide/*adverse effects ; }, abstract = {A small cohort of 194 men with low exposure to fibrous tremolite (mean 0.75 f/ml y) in the mining and milling of vermiculite in South Carolina experienced 51 deaths 15 years or more from first employment. The SMR (all causes) was 1.17 reflecting excess deaths from circulatory disease. There were four deaths from lung cancer and 3.31 expected (SMR 1.21, 95% CI 0.33-3.09). Three of the four deaths were in the lowest exposure category (less than 1 f/ml y); no death was attributed to mesothelioma or pneumoconiosis. These findings contrast with those in Montana where the vermiculite ore was heavily contaminated with fibrous tremolite. A radiographic survey of 86 current and recent South Carolina employees found four with small parenchymal opacities (greater than or equal to 1/0) and seven with pleural thickening. These proportions were not higher than in a non-exposed group and much lower than had been observed in Montana. Examination of sputum from 76 current employees showed that only two specimens contained typical ferruginous bodies, confirming low cumulative fibre exposure. Any possible adverse effects of work with vermiculite, minimally contaminated with fibrous or non-fibrous tremolite, were thus beyond the limits of detection in this workforce.}, } @article {pmid3293765, year = {1988}, author = {Fraire, AE and Cooper, S and Greenberg, SD and Buffler, P and Langston, C}, title = {Mesothelioma of childhood.}, journal = {Cancer}, volume = {62}, number = {4}, pages = {838-847}, doi = {10.1002/1097-0142(19880815)62:4<838::aid-cncr2820620433>3.0.co;2-9}, pmid = {3293765}, issn = {0008-543X}, mesh = {Adolescent ; Child ; Child, Preschool ; Female ; Global Health ; Humans ; Infant ; Male ; Mesothelioma/mortality/*pathology ; Peritoneal Neoplasms/mortality/*pathology ; Pleural Neoplasms/mortality/*pathology ; }, abstract = {Malignant mesothelioma (MM) of childhood is a rare but important neoplasm. Eighty children with a previous diagnosis of MM were identified. Four of the 80 children had exposure to known risk factors (two had history of exposure to asbestos, one had received radiation therapy, and one had been exposed in utero to isoniazid). Tissue slides were available for independent and joint review by a panel of three pathologists in 22 of the cases. Ten were accepted as MM, nine were reclassified as other malignancies, and three were considered tumors of uncertain nature. Six of the ten children with MM were boys, and four were girls. Eight had pleural tumors, and two had peritoneal tumors. Four died at 7, 8, 18, and 48 months after diagnosis; three remained alive at 19, 20, and 59 months; and three had no follow-up. This review suggests that MM of childhood is a valid entity with a grave prognosis. The tissue diagnosis is difficult and is best made by a panel of pathologists. The available evidence does not support a causal relationship between MM and asbestos, radiation, or isoniazid.}, } @article {pmid2840193, year = {1988}, author = {Kishimoto, T and Ono, T and Okada, K}, title = {Acute myelocytic leukemia after exposure to asbestos.}, journal = {Cancer}, volume = {62}, number = {4}, pages = {787-790}, doi = {10.1002/1097-0142(19880815)62:4<787::aid-cncr2820620424>3.0.co;2-8}, pmid = {2840193}, issn = {0008-543X}, mesh = {Aged ; Asbestos/*adverse effects ; Asbestos, Crocidolite ; Bone Marrow/ultrastructure ; Environmental Exposure ; Humans ; Leukemia, Myeloid, Acute/*etiology/pathology ; Lung/ultrastructure ; Lung Neoplasms/pathology ; Male ; Microscopy, Electron, Scanning ; Middle Aged ; }, abstract = {While the carcinogenicity of asbestos has been established in malignant mesotheliomas and lung cancers, and has recently been suspected in several other types of cancer, asbestos has not been implicated in the pathogenesis of acute leukemias. This article includes two cases of acute myelocytic leukemia in individuals with a long history of exposure to asbestos. Significant numbers of asbestos bodies were detected in specimens of their lungs and bone marrow. In addition, the kind of asbestos in both organs was crocidolite, which is implicated in carcinogenesis. No asbestos bodies were detected in the bone marrow specimens from a control group consisting of ten patients with lung cancer with similar occupational histories. The role of asbestos exposure in the development of leukemia requires further study.}, } @article {pmid3046649, year = {1988}, author = {Davis, JM and McDonald, JC}, title = {Low level exposure to asbestos: is there a cancer risk?.}, journal = {British journal of industrial medicine}, volume = {45}, number = {8}, pages = {505-508}, pmid = {3046649}, issn = {0007-1072}, mesh = {Animals ; Asbestos/administration & dosage/*adverse effects ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; }, } @article {pmid2837591, year = {1988}, author = {Langer, AM and Nolan, RP and Constantopoulos, SH}, title = {Endemic pleural calcification and mesothelioma.}, journal = {JAMA}, volume = {260}, number = {3}, pages = {339-340}, pmid = {2837591}, issn = {0098-7484}, mesh = {*Asbestos, Amphibole ; Calcinosis/*etiology ; Greece ; Humans ; Mesothelioma/*etiology ; Paint/adverse effects ; Pleural Diseases/*etiology ; Silicic Acid/*adverse effects ; Silicon Dioxide/*adverse effects ; }, } @article {pmid3398519, year = {1988}, author = {Morrow, JD}, title = {Asbestos and lung disease.}, journal = {Journal of the Tennessee Medical Association}, volume = {81}, number = {7}, pages = {449-450}, pmid = {3398519}, issn = {0040-3318}, mesh = {Asbestos/*adverse effects ; Humans ; Lung Neoplasms/diagnostic imaging/*etiology ; Male ; Mesothelioma/diagnostic imaging/*etiology ; Middle Aged ; Radiography ; }, } @article {pmid3395586, year = {1988}, author = {Huncharek, M and Smith, K and Milatou, R}, title = {Malignant pleural mesothelioma in a nuclear engineer.}, journal = {British journal of industrial medicine}, volume = {45}, number = {7}, pages = {498-499}, pmid = {3395586}, issn = {0007-1072}, mesh = {Asbestos/*adverse effects ; Engineering ; Humans ; Male ; Mesothelioma/*etiology ; Middle Aged ; Nuclear Reactors ; Occupational Diseases/*etiology ; Pleural Neoplasms/*etiology ; }, } @article {pmid3062345, year = {1988}, author = {Konietzko, N}, title = {[Asbestos and the lung. II].}, journal = {Medizinische Klinik (Munich, Germany : 1983)}, volume = {83}, number = {13-14}, pages = {449-455}, pmid = {3062345}, issn = {0723-5003}, mesh = {Asbestosis/*pathology ; Humans ; Lung/*pathology ; Mesothelioma/pathology ; Pleura/*pathology ; Pleural Neoplasms/pathology ; }, } @article {pmid3367951, year = {1988}, author = {Driscoll, RJ and Mulligan, WJ and Schultz, D and Candelaria, A}, title = {Malignant mesothelioma. A cluster in a native American pueblo.}, journal = {The New England journal of medicine}, volume = {318}, number = {22}, pages = {1437-1438}, doi = {10.1056/NEJM198806023182205}, pmid = {3367951}, issn = {0028-4793}, mesh = {Asbestos/analysis ; Culture ; Environmental Pollutants/analysis ; Humans ; *Indians, North American ; Mesothelioma/*epidemiology/etiology ; New Mexico ; Space-Time Clustering ; }, } @article {pmid3393849, year = {1988}, author = {Jones, RD and Smith, DM and Thomas, PG}, title = {Mesothelioma in Great Britain in 1968-1983.}, journal = {Scandinavian journal of work, environment & health}, volume = {14}, number = {3}, pages = {145-152}, doi = {10.5271/sjweh.1938}, pmid = {3393849}, issn = {0355-3140}, mesh = {Adult ; Age Factors ; Aged ; Computers ; Female ; Humans ; Male ; Mesothelioma/*mortality ; Middle Aged ; Peritoneal Neoplasms/mortality ; Pleural Neoplasms/mortality ; Registries ; Sex Factors ; United Kingdom ; }, abstract = {The British mesothelioma register records deaths in Great Britain when the word "mesothelioma" is on the death certificate. In 1968-1983 the mesothelioma deaths among men increased from 114 to 467, while those among women increased from 38 to 90. In 1983 the crude mesothelioma death rates were 17.5 per million and 3.2 per million for the men and women, respectively. The Northern region had the highest crude rates. At the county level, the highest crude deaths rates in 1976-1983 were recorded for the men in Devon and for the women in Lancashire. Marked differences occurred in the ratio of deaths among men to deaths among women for mesothelioma of the pleura (4.6:1) and for mesothelioma of the peritoneum (2:1). The age-specific death rates for men and women diverged markedly for pleural mesothelioma but not for peritoneal mesothelioma. Trends in the use of asbestos and in age- and sex-specific death rates suggest that the annual number of mesothelioma deaths will continue to increase, possibly until the turn of the century. This increase will be concentrated among the men as the main asbestos exposure of women occurred during the war and the annual deaths due to this exposure may have already peaked.}, } @article {pmid3375957, year = {1988}, author = {Faber, LP}, title = {Surgical treatment of asbestos-related disease of the chest.}, journal = {The Surgical clinics of North America}, volume = {68}, number = {3}, pages = {525-543}, doi = {10.1016/s0039-6109(16)44532-9}, pmid = {3375957}, issn = {0039-6109}, mesh = {Asbestos/*adverse effects ; Humans ; Lung Diseases/diagnostic imaging/etiology/*surgery ; Lung Neoplasms/diagnostic imaging/etiology/surgery/therapy ; Mesothelioma/diagnostic imaging/etiology/surgery/therapy ; Methods ; Pleural Diseases/diagnostic imaging/etiology/therapy ; Radiography ; }, abstract = {Thoracic surgeons are asked to evaluate various diseases related to asbestos, including benign pleural plaques, malignant mesothelioma, and lung cancer. The benign localized mesothelioma is usually considered in the differential diagnosis of pleural tumors, but it is not related to asbestos exposure. Benign pleural plaques can be diagnosed by history and radiologic studies, and surgery offers no therapeutic benefit. Diffuse malignant mesothelioma is currently an incurable tumor, but pleurectomy can afford some palliation. Extrapleural pneumonectomy can be accomplished with an acceptable mortality, but long-term results do not justify its routine use. Lung cancer in those exposed to asbestos fibers is treated no differently than when it occurs in the general population.}, } @article {pmid3293193, year = {1988}, author = {Pelnar, PV}, title = {Further evidence of nonasbestos-related mesothelioma. A review of the literature.}, journal = {Scandinavian journal of work, environment & health}, volume = {14}, number = {3}, pages = {141-144}, doi = {10.5271/sjweh.1939}, pmid = {3293193}, issn = {0355-3140}, mesh = {Animals ; Humans ; Mesothelioma/*etiology ; }, abstract = {Asbestos is not the only cause of malignant mesothelioma. An updated review of the literature is presented with reports on mesothelioma with unknown causes (spontaneous cases) in animals and humans and on mesothelioma in man in association with exposure to erionite-zeolite, exposure to ionizing radiation, and chronic inflammation and in animals in association with biological (viral), chemical, physicochemical, and physical agents.}, } @article {pmid3286241, year = {1988}, author = {Lippmann, M}, title = {Asbestos exposure indices.}, journal = {Environmental research}, volume = {46}, number = {1}, pages = {86-106}, doi = {10.1016/s0013-9351(88)80061-6}, pmid = {3286241}, issn = {0013-9351}, support = {CA 13343/CA/NCI NIH HHS/United States ; ES 00260/ES/NIEHS NIH HHS/United States ; ES 00881/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Asbestos/pharmacokinetics/*toxicity ; Asbestosis/etiology ; Environmental Exposure ; Humans ; Lung/metabolism ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Particle Size ; }, abstract = {The ability of inhaled asbestos to produce asbestosis, lung cancer, and mesothelioma in both humans and animals is well established, and asbestos exposures in the occupational and general community environment are recognized as significant hazards. However, it has not been possible to establish realistic and credible dose-response relationships, primarily because of our inability to define which constituents of the aerosols produce or initiate the pathological responses. It is generally acknowledged that the responses are associated with the fibers rather than the nonfibrous silicate mineral of the same chemical composition. Available data from experimental studies in animals exposed by injection and inhalation to fibers of defined size distributions are reviewed, alone with data from studies of fiber distributions in lungs of exposed humans in relation to the effects associated with the retained fibers. It is concluded that asbestosis is most closely related to the surface area of retained fibers, that mesothelioma is most closely associated with numbers of fibers longer than approximately 5 microns and thinner than approximately 0.1 micron, and that lung cancer is most closely associated with fibers longer than approximately 10 microns and thicker than approximately 0.15 micron. The implications of these conclusions on methods for fiber sampling and analyses are discussed.}, } @article {pmid2839650, year = {1988}, author = {Cooper, WC and Wong, O and Graebner, R}, title = {Mortality of workers in two Minnesota taconite mining and milling operations.}, journal = {Journal of occupational medicine. : official publication of the Industrial Medical Association}, volume = {30}, number = {6}, pages = {506-511}, pmid = {2839650}, issn = {0096-1736}, mesh = {Asbestos ; Asbestos, Amphibole ; Follow-Up Studies ; Humans ; *Iron ; Male ; *Minerals ; *Mining ; Minnesota ; Mortality ; Occupational Diseases/*mortality ; Risk Factors ; *Silicates ; Silicon Dioxide ; Time Factors ; }, abstract = {Mortality during the years 1947 to 1983 was studied in 3,444 men employed for at least 3 months in Minnesota taconite mining operations during the years 1947 to 1958. During 86,307 person-years of observation, there were 801 deaths for a standardized mortality ratio (SMR) of 88 (US white male rates) or 98 (Minnesota rates). The 41 deaths from respiratory cancer were fewer than expected, the SMR being 61 (P less than or equal to .01) (US rates) and 85 (Minnesota rates). There were 25 respiratory cancers 20 or more years after first taconite employment, for an SMR of 57 (P less than or equal to .01) (US rates). SMRs for colon cancer, kidney cancer, and lymphopoietic cancer were elevated, but below the level of statistical significance. There was one death from pleural mesothelioma, 11 years after first taconite employment, in a man with long prior employment as a locomotive operator. The pattern of deaths did not suggest asbestos-related disease in taconite miners and millers.}, } @article {pmid2453184, year = {1988}, author = {Plaus, WJ}, title = {Peritoneal mesothelioma.}, journal = {Archives of surgery (Chicago, Ill. : 1960)}, volume = {123}, number = {6}, pages = {763-766}, doi = {10.1001/archsurg.1988.01400300109019}, pmid = {2453184}, issn = {0004-0010}, mesh = {Adult ; Aged ; Antineoplastic Agents/therapeutic use ; Asbestosis/complications ; Ascites/complications/surgery ; Combined Modality Therapy ; Diagnosis, Differential ; Female ; Humans ; Laparoscopy ; Male ; Mesothelioma/blood supply/*diagnosis/therapy/ultrastructure ; Microscopy, Electron ; Middle Aged ; Palliative Care ; Peritoneal Neoplasms/blood supply/*diagnosis/therapy/ultrastructure ; Peritoneovenous Shunt/adverse effects ; }, abstract = {Peritoneal mesothelioma is a rare neoplasm often related to previous asbestos exposure. In 14 cases the diagnosis before surgery was virtually impossible, as patients presented with vague abdominal complaints and nonspecific physical examination findings. Laboratory testing (including computed tomography) was of no added diagnostic help. Widespread peritoneal neoplastic growth was the common finding at laparotomy. The tumor was grossly indistinguishable from other types of abdominal carcinomatosis. Electron microscopy proved to be the diagnostic tool of choice. Routine histologic techniques often gave nondiagnostic results. Intraperitoneal asbestos fibers were not observed. Treatment with radiation, chemotherapy, or both produced a 50% partial response rate, but survival was not affected. Malignant ascites was effectively palliated without complication in two of three patients with peritoneovenous shunting. An unusual case occurred in which histologic material from a second-look laparotomy documented complete response to a new regimen of intraperitoneal chemotherapy.}, } @article {pmid3131367, year = {1988}, author = {Berger, H}, title = {Of asbestosis, smoking, and mesothelioma.}, journal = {Hospital practice (Office ed.)}, volume = {23}, number = {5A}, pages = {17}, pmid = {3131367}, issn = {8750-2836}, mesh = {Air Pollutants, Occupational/*adverse effects ; Asbestos/*adverse effects ; Humans ; Mesothelioma/*etiology ; Smoking/*adverse effects ; }, } @article {pmid2966891, year = {1988}, author = {Taylor, PP}, title = {Malignant mesothelioma.}, journal = {The Medical journal of Australia}, volume = {148}, number = {10}, pages = {542}, doi = {10.5694/j.1326-5377.1988.tb99481.x}, pmid = {2966891}, issn = {0025-729X}, mesh = {Asbestos/*adverse effects ; Australia ; Humans ; Male ; Mesothelioma/*economics ; Middle Aged ; Peritoneal Neoplasms/*economics ; *Workers' Compensation ; }, } @article {pmid3359447, year = {1988}, author = {Schiffman, MH and Pickle, LW and Fontham, E and Zahm, SH and Falk, R and Mele, J and Correa, P and Fraumeni, JF}, title = {Case-control study of diet and mesothelioma in Louisiana.}, journal = {Cancer research}, volume = {48}, number = {10}, pages = {2911-2915}, pmid = {3359447}, issn = {0008-5472}, support = {N01-CP-61003/CP/NCI NIH HHS/United States ; N01-CP-91023/CP/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; *Diet ; Female ; Humans ; Louisiana ; Male ; Mesothelioma/*etiology ; Middle Aged ; Occupations ; Peritoneal Neoplasms/*etiology ; Pleural Neoplasms/*etiology ; Risk Factors ; Vegetables ; }, abstract = {Data were analyzed from a case-control interview study of malignant mesothelioma in Louisiana, which gathered information on usual diet and on lifetime occupational exposure to asbestos. Thirty-seven patients with malignant mesothelioma of the pleura (n = 32) or peritoneum (n = 5) were matched to controls according to age, sex, race, and factors related to case ascertainment (hospital and date of diagnosis, or parish and date of death). Twenty-one of the 37 cases were judged by masked occupational review to have been exposed to asbestos (57%), compared to seven of 37 controls (19%). Seven additional cases and 10 additional controls had occupational histories suggestive of asbestos exposure. With regard to usual diet before illness, cases reported less frequent consumption of homegrown produce (p = 0.005), cruciferous vegetables (p = 0.005), and all vegetables combined (p = 0.09) than did the controls. An estimate of usual carotene intake was also significantly lower in cases (p = 0.03). Dose-dependent reductions in risk were seen with increasing consumption of vegetables, especially cruciferous vegetables (p for trend = 0.013). These associations were not explained by differences in asbestos exposure as measured by the occupational review. The results indicate that consumption of vegetables or some vegetable-related constituent may have a protective effect on developing mesothelioma.}, } @article {pmid3282640, year = {1988}, author = {Gilks, B and Hegedus, C and Freeman, H and Fratkin, L and Churg, A}, title = {Malignant peritoneal mesothelioma after remote abdominal radiation.}, journal = {Cancer}, volume = {61}, number = {10}, pages = {2019-2021}, doi = {10.1002/1097-0142(19880515)61:10<2019::aid-cncr2820611015>3.0.co;2-k}, pmid = {3282640}, issn = {0008-543X}, mesh = {Combined Modality Therapy ; Dysgerminoma/*radiotherapy/surgery ; Female ; Humans ; Male ; Mesothelioma/*etiology ; Neoplasms, Multiple Primary/*etiology ; Neoplasms, Radiation-Induced/*etiology ; Orchiectomy ; Peritoneal Neoplasms/*etiology ; Radiotherapy/*adverse effects ; Radiotherapy Dosage ; Testicular Neoplasms/*radiotherapy/surgery ; }, abstract = {Peritoneal mesothelioma in a 61-year-old man, occurred 26 years after abdominal radiotherapy for a testicular seminoma. The patient had no history of asbestos exposure. After asbestos, radiation is the second most frequent defined cause of mesothelioma in North America, but the number of well-documented cases is small; this case represents only the fifth example of peritoneal mesothelioma after therapeutic irradiation of the abdomen.}, } @article {pmid3383800, year = {1988}, author = {Luther, R and Wetzer, K and Kühne, W and Spormann, H and Böttger, W}, title = {Asbestos-induced pleural diseases--thoracoscopic aspects.}, journal = {Endoscopy}, volume = {20}, number = {3}, pages = {104-106}, doi = {10.1055/s-2007-1018148}, pmid = {3383800}, issn = {0013-726X}, mesh = {Aged ; Asbestos/*adverse effects ; Asbestosis/pathology ; Diagnosis, Differential ; Humans ; Male ; Mesothelioma/etiology/pathology ; Middle Aged ; Pleural Diseases/etiology/*pathology ; Pleural Neoplasms/etiology/pathology ; Pleurisy/etiology/pathology ; Thoracoscopy ; }, abstract = {The endoscopic morphology of asbestos-induced pleural disease is demonstrated by typical thoracoscopic findings. Among 627 thoracoscopies, lesions induced by exposure to asbestos were found in 9.9% (50 malignant mesotheliomas of the pleura, 10 pleural hyalinoses, 2 asbestos pleurisies). This comparatively high percentage is indicative of the pathogenic relevance of asbestos in the pleuropulmonary region. In addition to describing the diffuse malignant mesotheliomas of the pleura, reference is made in the discussion to the possible occurrence of benign localized fibromatous mesotheliomas that are not clearly related to asbestos exposure.}, } @article {pmid3378009, year = {1988}, author = {Wagner, JC and Newhouse, ML and Corrin, B and Rossiter, CE and Griffiths, DM}, title = {Correlation between fibre content of the lung and disease in east London asbestos factory workers.}, journal = {British journal of industrial medicine}, volume = {45}, number = {5}, pages = {305-308}, pmid = {3378009}, issn = {0007-1072}, mesh = {Asbestosis/complications/*pathology ; Female ; Humans ; London ; Lung/*pathology ; Lung Neoplasms/etiology ; Male ; Mesothelioma/etiology ; Middle Aged ; Peritoneal Neoplasms/etiology ; Pleural Neoplasms/etiology ; }, abstract = {The lungs from 36 past workers at an east London asbestos factory who had died from asbestos related disease were compared with lung tissue from 56 matched control patients being operated on in east London for carcinoma of the lung, correlating the severity of asbestosis and the presence of pulmonary carcinoma or mesothelioma of the pleura or peritoneum with an asbestos exposure index and type and amount of mineral fibre in the lungs. Asbestosis was associated with far heavier fibre burdens than mesothelioma. There was also a striking difference in the degree of asbestosis between the subjects with mesothelioma and those with carcinoma of the lung, the asbestosis being more severe in the latter. A further finding was that crocidolite and amosite were strongly associated with asbestosis, carcinoma of the lung complicating asbestosis, and mesothelioma, whereas no such correlation was evident with chrysotile or mullite. It is suggested that more emphasis should be placed on the biological differences between amphibole and serpentine asbestos fibre.}, } @article {pmid3378008, year = {1988}, author = {Lilienfeld, DE and Mandel, JS and Coin, P and Schuman, LM}, title = {Projection of asbestos related diseases in the United States, 1985-2009. I. Cancer.}, journal = {British journal of industrial medicine}, volume = {45}, number = {5}, pages = {283-291}, pmid = {3378008}, issn = {0007-1072}, support = {ES00161/ES/NIEHS NIH HHS/United States ; }, mesh = {Asbestos/*adverse effects ; Forecasting ; Gastrointestinal Neoplasms/etiology/mortality ; Humans ; Lung Neoplasms/etiology/*mortality ; Mesothelioma/etiology/*mortality ; Occupational Diseases/etiology/*mortality ; United States ; }, abstract = {Projections of asbestos associated cancer mortality in the United States during the 25 year period 1985-2009 were made based on previously published estimates. These estimates were reviewed for malignant mesothelioma, lung cancer, and gastrointestinal cancers. Particular attention was given to the assumptions used in the original derivation of the estimates. For malignant mesothelioma mortality, previous estimates ranged from 15,500 to 300,000. Using recently published data from the Surveillance, Epidemiology, and End Results project, coupled with the previously published estimates, projected asbestos related malignant mesothelioma mortality in the United States for the period 1985-2009 was estimated to be 21,500. For lung cancer, previous estimates were reviewed, particularly with regard to the ratio of deaths from lung cancer to deaths from malignant mesothelioma. Using these ratios, a range of projected deaths was established and a median of those estimates used as a project, which was 76,700 such deaths in the United States between 1985 and 2009. Gastrointestinal cancer mortality has been projected by only three investigators. A median of those estimates (33,000) was used. In conclusion it is estimated that 131,200 deaths from asbestos associated cancer will occur in the United States between 1985 and 2009.}, } @article {pmid3175139, year = {1988}, author = {Bombí, JA and Xaubet, A and Letang, E and Ribalta, T and Picado, C and Agustí Vidal, A and Sánchez-Lloret, J and Cardesa, A}, title = {[Clinicopathological study of 23 pleural malignant mesotheliomas].}, journal = {Revista clinica espanola}, volume = {182}, number = {9}, pages = {464-470}, pmid = {3175139}, issn = {0014-2565}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Combined Modality Therapy ; Female ; Humans ; Male ; Mesothelioma/classification/diagnosis/*pathology/therapy ; Middle Aged ; Pleural Effusion/etiology ; Pleural Neoplasms/diagnosis/*pathology/therapy ; Prognosis ; Retrospective Studies ; }, } @article {pmid3067983, year = {1988}, author = {Talcott, JA and Antman, KH}, title = {Asbestos-related malignancy.}, journal = {Current problems in cancer}, volume = {12}, number = {3}, pages = {135-178}, doi = {10.1016/s0147-0272(88)80005-9}, pmid = {3067983}, issn = {0147-0272}, mesh = {Asbestos/*adverse effects ; Environmental Exposure/legislation & jurisprudence ; Humans ; *Lung Neoplasms/etiology ; *Mesothelioma/etiology ; Neoplasms/*etiology ; }, abstract = {Asbestos-associated malignancies have received significant attention in the lay and medical literature because of the increasing frequency of two asbestos-associated tumors, lung carcinoma and mesothelioma; the wide distribution of asbestos; its status as a prototype environmental carcinogen; and the many recent legal compensation proceedings, for which medical testimony has been required. The understanding of asbestos-associated carcinogenesis has increased through study of animal models, human epidemiology, and, recently, the application of modern molecular biological techniques. However, the detailed mechanisms of carcinogenesis remain unknown. A wide variety of malignancies have been associated with asbestos, although the strongest evidence for a causal association is confined to lung cancer and mesothelioma. Epidemiological studies have provided evidence that both the type of asbestos fiber and the industry in which the exposure occurs may affect the rates of asbestos-associated cancers. It has been shown that asbestos exerts a carcinogenic effect independent of exposure to cigarette smoking that, for lung cancers, is synergistically enhanced by smoking. Other questions remain controversial, such as whether pulmonary fibrosis necessarily precedes asbestos-associated lung cancer and whether some threshold level of exposure to asbestos (including low-dose exposures that may occur in asbestos-associated public buildings) may be safe. Mesothelioma, the most closely asbestos-associated malignancy, has a dismal natural history and has been highly resistant to therapy. However, investigational multi-modality therapy may offer benefit to some patients. A description of the processes through which compensation claims for asbestos-associated malignancies are evaluated illustrates for physicians the legal system's approach to possible injury from toxic substances. The differences between scientific and legal reasoning about the causes of diseases with long latency, especially when they are imputed to toxic exposures are substantial, and may impede the application of toxicological evidence to legal disputes.}, } @article {pmid3356487, year = {1988}, author = {Spirtas, R and Connelly, RR and Tucker, MA}, title = {Survival patterns for malignant mesothelioma: the SEER experience.}, journal = {International journal of cancer}, volume = {41}, number = {4}, pages = {525-530}, doi = {10.1002/ijc.2910410409}, pmid = {3356487}, issn = {0020-7136}, mesh = {Adult ; Age Factors ; Aged ; Asbestos/toxicity ; Female ; Humans ; Male ; Mesothelioma/etiology/*mortality/therapy ; Middle Aged ; Sex Factors ; }, abstract = {Statistical analyses of 1,475 histologically confirmed cases of malignant mesothelioma ascertained through the Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute for the years 1973-1984 showed age at diagnosis, sex, stage of disease, type of treatment, and geographic area of residence to be important predictors of patient survival, although type of treatment may be confounded with prognostic factors (patients selected for surgical treatment tended to have better performance status than other patients). Women below the age of 50 had an unusually long survival, even after adjustment for the effects of other variables in the model. A relatively large proportion of female cases had site of disease designated as peritoneum, but site was not a significant prognostic factor. These results suggest that age, gender and stage of disease should be carefully considered in designing and analyzing clinical trials for persons with mesothelioma. Survival was shorter in the 4 SEER registries which had shipbuilding as a major industry than in the others with less potential asbestos exposure, offering weak support for the hypothesis that asbestos-exposed cases of mesothelioma have worse survival experience than other cases.}, } @article {pmid3348994, year = {1988}, author = {Ribak, J and Lilis, R and Suzuki, Y and Penner, L and Selikoff, IJ}, title = {Malignant mesothelioma in a cohort of asbestos insulation workers: clinical presentation, diagnosis, and causes of death.}, journal = {British journal of industrial medicine}, volume = {45}, number = {3}, pages = {182-187}, pmid = {3348994}, issn = {0007-1072}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Cause of Death ; Humans ; Male ; Mesothelioma/*diagnosis/mortality ; Middle Aged ; Occupational Diseases/*diagnosis/mortality ; Peritoneal Neoplasms/*diagnosis/mortality ; Pleural Neoplasms/*diagnosis/mortality ; Prospective Studies ; }, abstract = {Malignant mesothelioma has been rare in the general population. In recent decades its incidence has risen dramatically, parallel to the increasing use of asbestos in industry since 1930. Altogether 17,800 asbestos insulation workers, members of the International Association of Heat and Frost Insulators and Asbestos Workers (AFL-CIO-CLC) in the United States and Canada, were enrolled for prospective study on 1 January 1967 and followed up to the present. Every death that occurs is investigated by our laboratory. One hundred and seventy five deaths from mesothelioma occurred among the 2221 men who died in 1967-76 and 181 more such deaths in the next eight years. Altogether, 356 workers had died of malignant mesothelioma (pleural or peritoneal) by 1984. Diagnosis of mesothelioma was accepted only after all available clinical, radiological, and pathological material was reviewed by our laboratory and histopathological confirmation by the pathology unit made in each case. One hundred and thirty four workers died of pleural and 222 of peritoneal mesothelioma. Age at onset of exposure, age at onset of the disease, and age at death were similar in both groups of patients. Significant difference was noted only in the time elapsed from onset of exposure to the development of first symptoms, which was longer in the group with peritoneal mesothelioma. Shortness of breath, either new or recently increased, and chest pain were the most frequent presenting symptoms in the group with pleural mesothelioma; abdominal pain and distension were frequent in the patients with peritoneal mesothelioma. Pleural effusion or ascites were found in most patients. The most effective approach to the diagnosis of malignant pleural mesothelioma in these cases was by open lung biopsy; exploratory laparotomy was best for diagnosing peritoneal mesothelioma. Patients with pleural mesothelioma died principally from pulmonary insufficiency whereas those with peritoneal mesothelioma succumbed after a period of pronounced wasting.}, } @article {pmid3341358, year = {1988}, author = {Teta, MJ and Ott, MG}, title = {A mortality study of a research, engineering, and metal fabrication facility in western New York State.}, journal = {American journal of epidemiology}, volume = {127}, number = {3}, pages = {540-551}, doi = {10.1093/oxfordjournals.aje.a114829}, pmid = {3341358}, issn = {0002-9262}, mesh = {Actuarial Analysis ; Asbestos/adverse effects ; Carbon Tetrachloride Poisoning/mortality ; Cardiovascular Diseases/etiology/mortality ; Humans ; Liver Cirrhosis/etiology/mortality ; Male ; *Metallurgy ; *Mortality ; Neoplasms/etiology/mortality ; New York ; Occupational Diseases/etiology/*mortality ; Radioactive Pollutants/adverse effects ; }, abstract = {The mortality experience of 8,146 male employees of a research, engineering, and metal fabrication facility in Tonawanda, New York state was examined from 1946 to 1981. Potential workplace exposures included welding fumes, cutting oils, asbestos, organic solvents, and environmental ionizing radiation, as the result of disposal of wastes during the Manhattan Project of World War II. External comparisons with the US male population were supplemented by regional comparisons. For the total cohort, deficits were observed for all causes of death (standardized mortality ratio (SMR) = 87) and most non-cancer causes. The observed number of cancer deaths was close to expected (SMR = 99). There was an excess of connective and soft tissue cancer deaths, most notably in hourly employees hired prior to 1946. Among all hourly employees, there was an excess of respiratory cancer, which did not appear to be associated with length of employment. Mesothelioma was recorded as the cause of death for three decedents, two of whom were hourly employees who worked in production areas with high potential for asbestos exposure. The standardized mortality ratio for cirrhosis of the liver was elevated among long-term hourly employees hired prior to 1946. The roles of carbon tetrachloride exposure in the 1940s and alcohol consumption are discussed as possible contributory risk factors for the cirrhosis findings. The data do not provide evidence of radiation-induced cancers within this employee population.}, } @article {pmid2830081, year = {1988}, author = {Churg, A}, title = {Chrysotile, tremolite, and malignant mesothelioma in man.}, journal = {Chest}, volume = {93}, number = {3}, pages = {621-628}, doi = {10.1378/chest.93.3.621}, pmid = {2830081}, issn = {0012-3692}, mesh = {Asbestos/*adverse effects ; *Asbestos, Amphibole ; Asbestos, Serpentine ; Dose-Response Relationship, Drug ; Humans ; Lung Neoplasms/*chemically induced/epidemiology ; Mesothelioma/*chemically induced/epidemiology ; Mining ; Occupational Diseases/*chemically induced/epidemiology ; Particle Size ; Risk Factors ; Silicic Acid/*adverse effects ; Silicon Dioxide/*adverse effects ; Textile Industry ; }, abstract = {The question of whether chrysotile asbestos ever causes mesothelioma in man has become a major public and occupational health issue. Review of the literature suggests that only 53 acceptable cases of chrysotile-induced mesothelioma have ever been reported; of these, 41 cases have occurred in individuals exposed to chrysotile mine dust, all of it naturally contaminated with tremolite. Ten cases have occurred in secondary industry workers, but here the suspicion of amosite or crocidolite contamination is high. Analysis of lung asbestos content indicates that induction of mesothelioma by chrysotile requires, on average, as great a lung fiber burden as induction of asbestosis by chrysotile, whereas amphibole (amosite or crocidolite)-induced mesotheliomas appear at a several hundred-fold smaller lung burden. Tremolite alone has definitely produced mesothelioma in man, particularly when exposure has been to long, high aspect ratio, fibers. Analysis of tremolite:chrysotile fiber ratios in human lung suggests that some, but not all tremolite is removed in milling chrysotile ores. The low incidence of mesothelioma in secondary chrysotile users may reflect the small amount of tremolite left in the product. These observations indicate that although chrysotile asbestos can produce mesothelioma in man, the total number of such cases is small and the required doses extremely large. The data are consistent with the idea that mesotheliomas seen in chrysotile miners and some secondary industry workers are produced by the tremolite contained in the chrysotile ore, but that the short length and low aspect ratio of the tremolite make its carcinogenicity quite low. However, these data are very indirect, and a role for the chrysotile fiber itself is still possible.}, } @article {pmid3277382, year = {1988}, author = {Craighead, JE}, title = {1987 H. P. Smith award lecture. Eyes for the epidemiologist: the pathologist's role in shaping our understanding of the asbestos-associated diseases.}, journal = {American journal of clinical pathology}, volume = {89}, number = {2}, pages = {281-287}, doi = {10.1093/ajcp/89.2.281}, pmid = {3277382}, issn = {0002-9173}, mesh = {Asbestos/*adverse effects/history ; Asbestosis/chemically induced/history/pathology ; *Awards and Prizes ; Carcinoma, Bronchogenic/etiology/pathology ; England ; Epidemiology/history ; Germany ; History, 19th Century ; History, 20th Century ; Humans ; Lung Neoplasms/etiology/pathology ; Mesothelioma/chemically induced/pathology ; Pathology/history ; United States ; }, abstract = {Asbestosis was first recognized as an entity at autopsy by a pathologist in 1900. Pathologists also discovered the unique relationship of mesothelioma and bronchogenic carcinoma with exposure to asbestos. The observations of preceding pathologists have provided insights that have served as the basis for epidemiologic studies associating asbestos with disease in humans.}, } @article {pmid2826831, year = {1988}, author = {}, title = {Endemic pleural calcification and mesothelioma.}, journal = {JAMA}, volume = {259}, number = {4}, pages = {520}, pmid = {2826831}, issn = {0098-7484}, mesh = {Asbestos/*adverse effects ; *Asbestos, Amphibole ; Calcinosis/*epidemiology ; Environmental Exposure ; Humans ; Mesothelioma/*etiology ; Pleural Diseases/*epidemiology ; Pleural Neoplasms/*etiology ; Silicic Acid/*adverse effects ; Silicon Dioxide/*adverse effects ; }, } @article {pmid3336327, year = {1988}, author = {Barnes, R}, title = {Notification of malignant mesotheliomas.}, journal = {The Medical journal of Australia}, volume = {148}, number = {2}, pages = {106-107}, doi = {10.5694/j.1326-5377.1988.tb104543.x}, pmid = {3336327}, issn = {0025-729X}, mesh = {Asbestos/adverse effects ; Australia ; Humans ; *Lung Neoplasms ; *Mesothelioma ; *Occupational Diseases ; *Registries ; }, } @article {pmid3389368, year = {1988}, author = {Michaels, D and Zoloth, S}, title = {Asbestos disease in sheet metal workers: proportional mortality update.}, journal = {American journal of industrial medicine}, volume = {13}, number = {6}, pages = {731-734}, doi = {10.1002/ajim.4700130612}, pmid = {3389368}, issn = {0271-3586}, mesh = {Actuarial Analysis ; Asbestos/*adverse effects ; Humans ; Lung Neoplasms/etiology/*mortality ; Male ; Mesothelioma/etiology/*mortality ; *Metallurgy ; Neoplasms/etiology/*mortality ; New York City ; Occupational Diseases/etiology/*mortality ; }, abstract = {This paper, updating the findings of an earlier study, provides additional evidence that sheet metal workers in the construction trades are at increased risk for asbestos-related disease. A proportional analysis of cause of death among 331 New York sheet metal workers found a significantly elevated PMR for lung cancer (PMR = 186). In addition, there were six deaths attributable to mesothelioma (three classified as lung cancer deaths) and three death certificates mentioned asbestosis or pulmonary fibrosis, although none of these three deaths were attributed to these diseases.}, } @article {pmid3376945, year = {1988}, author = {Järvholm, B and Malker, H and Malker, B and Ericsson, J and Sällsten, G}, title = {Pleural mesotheliomas and asbestos exposure in the pulp and paper industries: a new risk group identified by linkage of official registers.}, journal = {American journal of industrial medicine}, volume = {13}, number = {5}, pages = {561-567}, doi = {10.1002/ajim.4700130504}, pmid = {3376945}, issn = {0271-3586}, mesh = {Asbestos/*adverse effects ; Environmental Exposure ; Female ; Humans ; *Industry ; Male ; Mesothelioma/*etiology/pathology ; *Paper ; Pleural Neoplasms/*etiology/pathology ; Registries ; Risk Factors ; Sweden ; }, abstract = {Analysis of data obtained by linking the 1960 Swedish Census and the Swedish Cancer Registry has demonstrated an increased risk of pleural mesothelioma among pulp and paper workers. The present study was undertaken with the aim of revealing possible environmental risk factors. The work histories of the 25 cases identified earlier were reviewed. "Certain" or "probable" exposure to asbestos was found among 70% of these workers. The study illustrates how linkage of official registers can be used to identify new risk environments and encourage the establishment of preventive measures.}, } @article {pmid3335148, year = {1988}, author = {Chailleux, E and Dabouis, G and Pioche, D and de Lajartre, M and de Lajartre, AY and Rembeaux, A and Germaud, P}, title = {Prognostic factors in diffuse malignant pleural mesothelioma. A study of 167 patients.}, journal = {Chest}, volume = {93}, number = {1}, pages = {159-162}, doi = {10.1378/chest.93.1.159}, pmid = {3335148}, issn = {0012-3692}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Mesothelioma/mortality/*pathology/therapy ; Middle Aged ; Pleural Neoplasms/mortality/*pathology/therapy ; Prognosis ; }, abstract = {The existence of large shipyards accounts for the particular frequency of pleural mesothelioma in the Nantes-St. Nazaire region of France. From 1955 to 1985, 167 cases were diagnosed. Occupational exposure to asbestos was involved in 131 cases (88 percent). There was a great predominance of epithelial types (135) over mixed (25) and fibrosarcomatous (7) types. Survival, estimated by the actuarial method, was 54 percent at one year from first symptoms and 39 percent from histologic diagnosis. No subject was alive four years after diagnosis. Histologic type and asbestos exposure had no predictive value in our series. Survival was longer in patients under 60 years of age and when mesothelioma originated on the left side. Overall, treated patients had significantly longer survival than untreated patients. However, there was no significant difference in survival with respect to the type of treatment given: surgery, chemotherapy, talc poudrage or their combination.}, } @article {pmid3334988, year = {1988}, author = {Popescu, NC and Chahinian, AP and DiPaolo, JA}, title = {Nonrandom chromosome alterations in human malignant mesothelioma.}, journal = {Cancer research}, volume = {48}, number = {1}, pages = {142-147}, pmid = {3334988}, issn = {0008-5472}, support = {CA 36283/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; *Chromosome Aberrations ; Chromosome Deletion ; Chromosomes, Human, Pair 1 ; Chromosomes, Human, Pair 3 ; Chromosomes, Human, Pair 7 ; Female ; Humans ; Male ; Mesothelioma/*genetics ; Middle Aged ; Proto-Oncogenes ; Tumor Cells, Cultured ; }, abstract = {Malignant mesothelioma (MM) is a neoplasm closely associated with asbestos exposure, which has been implicated in 70-80% of the cases. In this study, nine MM (two fresh surgical specimens, two permanent cell lines, and five xenografts in nude mice) were examined cytogenetically. Six patients had a known history of asbestos exposure. Seven MM were chromosomally abnormal, the majority having complex structural alterations affecting different chromosomes, whereas two fresh surgical specimens had a normal chromosome constitution. Alterations of chromosome 3 were detected in seven cases and changes involving chromosomes 1 and 7 were observed in six cases. The breakpoints of translocations and deletions on chromosome 1 involved several bands; however, 50% of the breakpoints were near the locations of Blym, L-myc, and ski protooncogenes. Forty % of the breaks on chromosome 7 involved bands q11.1-11.2 and 20% were at q22, the location of the met protooncogene. Nonrandom changes on chromosome 3 were interstitial or terminal deletions, and translocations involving the region p14-21. The deleted 3p segment was identifiable as part of a chromosome translocation in one MM and was apparently lost in the other six. The deletions involving 3p are either spontaneous or asbestos-induced lesions at vulnerable genomic sites and are the most common and nonrandom chromosome alterations observed. Possibly 3p abnormalities are causally related to the development of this malignancy.}, } @article {pmid3147172, year = {1988}, author = {Navrátil, M and Morávková, K and Gafronová, M and Hruska, F}, title = {The fate of people with pleural hyalinosis (plaques): relationship to direct and indirect asbestos exposure.}, journal = {Czechoslovak medicine}, volume = {11}, number = {3}, pages = {146-156}, pmid = {3147172}, issn = {0139-9179}, mesh = {Aged ; Air Pollutants, Occupational ; Asbestosis/complications/*diagnostic imaging/mortality/pathology ; Cause of Death ; Environmental Exposure ; Female ; Follow-Up Studies ; Humans ; Male ; Pleura/*diagnostic imaging/pathology ; Radiography ; }, abstract = {A follow-up study of persons with pleural plaques was concluded in 1984. The first cohort was made up of employees and retired workers with direct absestos exposure in an asbestos factory (AZ factory) producing heat-resistant textiles, friction engine parts and heat-resistant boards. The raw material was imported chrysotile and small amounts of crocidolite. The follow-up was started in the 1950s. Our second cohort comprised residents selected by radiographic screening in a vast area surrounding the AZ factory who had had indirect asbestos exposure by airborn asbestos fibres. The follow-up period began in the 1970s. A control group consisted of employees and retired workers of a railway repair shop, without exposure to asbestos dust and within a corresponding age bracket. At the time of assessing our results, most of the subjects assigned to all the three groups were no longer alive so we were able to analyse data regarding their life and death. Hyalinosis complicata and pleural mesothelioma (peritoneal mesothelioma in one case) were present and resulted in death only in those with direct asbestos exposure. While lung cancer was among the causes of death in both cohorts with exposure as well as in the control group, its prevalence in the group with direct exposure was significantly higher than in the control group. By contrast, "other neoplasia" was found both in the control group and in exposed persons without any specific prevalence.}, } @article {pmid3076934, year = {1988}, author = {Weill, H and Hughes, JM}, title = {Asbestos health effects: resolving the scientific uncertainties.}, journal = {Postgraduate medical journal}, volume = {64 Suppl 4}, number = {}, pages = {48-55}, pmid = {3076934}, issn = {0032-5473}, mesh = {Asbestos/*adverse effects ; Asbestosis ; Humans ; Lung Neoplasms/etiology ; Male ; Mesothelioma/etiology ; Occupational Diseases/etiology ; }, } @article {pmid3068933, year = {1988}, author = {Kühne, W and Schultz, M}, title = {[Asbestos-induced malignant tumors].}, journal = {Zentralblatt fur allgemeine Pathologie u. pathologische Anatomie}, volume = {134}, number = {8}, pages = {703-712}, pmid = {3068933}, issn = {0044-4030}, mesh = {Asbestos/*adverse effects ; Carcinoma, Bronchogenic/*etiology ; Gastrointestinal Neoplasms/etiology ; Humans ; Lung Neoplasms/etiology ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; Peritoneal Neoplasms/etiology ; Pleural Neoplasms/etiology ; Respiratory Tract Neoplasms/*etiology ; }, abstract = {Asbestos had been increasingly used in many applications across numerous industries on account of its particular material properties, including resistance to heat and fire as well as to aggressive chemicals, high mechanical strength, insulation capacity, other physical parameters, and for its low price. World wide asbestos production and processing thus went up from 50 tons to 5.5 million tons per annum, in about 100 years. Widespread application of asbestos as well as of asbestos-containing materials and workpieces together with the understanding that asbestos for its fibrogenicity is capable of causing pulmonary and pleural asbestoses constitute a major challenge for thorough elucidation of related occupational diseases and their relationship with asbestos. This demand is additionally supported in urgency by the cancerogenicity of asbestos potentially leading to malignant diffuse mesotheliomas, bronchial carcinomas, and, obviously, other tumors. In the context of malignant mesotheliomas, emphasis has to be laid on characteristic morphological features, biological behaviours, and asbestos-related aetiology. As bronchial carcinomas have several aetiological backgrounds, answers will have to be found to the questions for which of them may have been fully or partially caused by asbestos and which have not. No differentiation has so far been feasible, in this context, by tumour morphology, including histological typing. After all, when it comes to malignant tumours of other organs, additional epidemiological as well as pathologico-anatomic efforts will have to be made to find out, if and where a given case of tumour growth has coincided with exposure to asbestos.}, } @article {pmid3064250, year = {1988}, author = {Chailleux, E and Rembeaux, A and de Lajartre, AY and Delumeau, J}, title = {[Benign pleural pathology of asbestos].}, journal = {Revue de pneumologie clinique}, volume = {44}, number = {4}, pages = {166-180}, pmid = {3064250}, issn = {0761-8417}, mesh = {*Asbestosis/diagnosis/epidemiology/etiology ; France ; Humans ; Legislation, Medical ; Occupational Diseases/etiology ; *Pleural Diseases/diagnosis/epidemiology/etiology ; Prognosis ; Pulmonary Atelectasis/etiology ; Pulmonary Fibrosis/etiology ; Respiratory Function Tests ; }, abstract = {The most frequent benign lesions of the pleura created by asbestos are fibro-hyaline plaques, i.e. thick areas of collagen located on the parietal pleura and gradually becoming calcified. Less common is benign pleural effusion the cause of which is not always easy to determine. To these must be added an extensive pleural fibrosis with functional repercussions that are not negligible, and round pseudotumoral atelectasias. These pleural asbestos-induced lesions are often observed after a low intensity exposure, but they appear as a rule after more than 20 years of latency. While they betray a previous exposure to asbestos, they also raise the problem of possible asbestos-induced lung cancer and mesothelioma.}, } @article {pmid2852472, year = {1988}, author = {Sluis-Cremer, GK}, title = {Linking chrysotile asbestos with mesothelioma.}, journal = {American journal of industrial medicine}, volume = {14}, number = {5}, pages = {631-632}, doi = {10.1002/ajim.4700140514}, pmid = {2852472}, issn = {0271-3586}, mesh = {Asbestos/*adverse effects ; *Asbestos, Amphibole ; Asbestos, Serpentine ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; Silicic Acid/adverse effects ; }, } @article {pmid2852471, year = {1988}, author = {Davis, JM}, title = {On the statement by Jacques Dunnigan.}, journal = {American journal of industrial medicine}, volume = {14}, number = {5}, pages = {629-630}, doi = {10.1002/ajim.4700140513}, pmid = {2852471}, issn = {0271-3586}, mesh = {Asbestos/*adverse effects ; Asbestos, Serpentine ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; }, } @article {pmid2852470, year = {1988}, author = {Lilienfeld, DE}, title = {Obfuscation: a reply to Dr. Dunnigan.}, journal = {American journal of industrial medicine}, volume = {14}, number = {5}, pages = {625-628}, doi = {10.1002/ajim.4700140512}, pmid = {2852470}, issn = {0271-3586}, mesh = {Asbestos/*adverse effects ; Asbestos, Serpentine ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; }, } @article {pmid2849874, year = {1988}, author = {McDonald, JC}, title = {Tremolite, other amphiboles, and mesothelioma.}, journal = {American journal of industrial medicine}, volume = {14}, number = {2}, pages = {247-249}, doi = {10.1002/ajim.4700140223}, pmid = {2849874}, issn = {0271-3586}, mesh = {Asbestos, Amphibole ; Asbestosis/*etiology ; Humans ; Mesothelioma/*etiology ; Pleural Neoplasms/*etiology ; Risk Factors ; Silicic Acid/*adverse effects ; Silicon Dioxide/*adverse effects ; }, } @article {pmid2849873, year = {1988}, author = {Roggli, VL and Pratt, PC}, title = {Amphiboles and chrysotile asbestos exposure.}, journal = {American journal of industrial medicine}, volume = {14}, number = {2}, pages = {245-246}, doi = {10.1002/ajim.4700140222}, pmid = {2849873}, issn = {0271-3586}, mesh = {Asbestos/*adverse effects ; Asbestos, Amphibole ; Asbestos, Serpentine ; Asbestosis/*etiology ; Humans ; Mesothelioma/*etiology ; Pleural Neoplasms/*etiology ; Risk Factors ; Silicon Dioxide/*adverse effects ; }, } @article {pmid2849872, year = {1988}, author = {Craighead, JM}, title = {Response to Dr. Dunnigan's commentary. The role of chrysotile in the pathogenesis of mesothelioma.}, journal = {American journal of industrial medicine}, volume = {14}, number = {2}, pages = {241-243}, doi = {10.1002/ajim.4700140221}, pmid = {2849872}, issn = {0271-3586}, mesh = {Animals ; Asbestos/*adverse effects ; Asbestos, Serpentine ; Asbestosis/*etiology ; Humans ; Mesothelioma/*etiology ; Pleural Neoplasms/*etiology ; Risk Factors ; }, } @article {pmid2849871, year = {1988}, author = {Becklake, MR}, title = {On Dr. Dunnigan's commentary linking chrysotile asbestos with mesothelioma.}, journal = {American journal of industrial medicine}, volume = {14}, number = {2}, pages = {239-240}, doi = {10.1002/ajim.4700140220}, pmid = {2849871}, issn = {0271-3586}, mesh = {Asbestos/*adverse effects ; Asbestos, Serpentine ; Asbestosis/*etiology ; Humans ; Mesothelioma/*etiology ; Pleural Neoplasms/*etiology ; Risk Factors ; }, } @article {pmid2849870, year = {1988}, author = {Churg, A}, title = {Reply to Dr. Dunnigan. Chrysotile as a mesothelial carcinogen in man.}, journal = {American journal of industrial medicine}, volume = {14}, number = {2}, pages = {235-238}, doi = {10.1002/ajim.4700140219}, pmid = {2849870}, issn = {0271-3586}, mesh = {Asbestos/*adverse effects ; Asbestos, Serpentine ; Asbestosis/*etiology ; Humans ; Mesothelioma/*etiology ; Pleural Neoplasms/*etiology ; Risk Factors ; }, } @article {pmid2849869, year = {1988}, author = {Dunnigan, J}, title = {Linking chrysotile asbestos with mesothelioma.}, journal = {American journal of industrial medicine}, volume = {14}, number = {2}, pages = {205-209}, doi = {10.1002/ajim.4700140211}, pmid = {2849869}, issn = {0271-3586}, mesh = {Asbestos/*adverse effects ; Asbestos, Serpentine ; Asbestosis/*pathology ; Humans ; Lung/pathology ; Lung Neoplasms/*pathology ; Male ; Mesothelioma/*pathology ; Pleura/pathology ; Pleural Neoplasms/*pathology ; }, } @article {pmid2839879, year = {1988}, author = {Fasske, E}, title = {Experimental lung tumors following specific intrabronchial application of chrysotile asbestos. Longitudinal light and electron microscopic investigations in rats.}, journal = {Respiration; international review of thoracic diseases}, volume = {53}, number = {2}, pages = {111-127}, doi = {10.1159/000195403}, pmid = {2839879}, issn = {0025-7931}, mesh = {Adenocarcinoma/*etiology/ultrastructure ; Animals ; Asbestos/*toxicity ; Asbestos, Serpentine ; Benzo(a)pyrene/toxicity ; Female ; Lung/*ultrastructure ; Lung Neoplasms/*etiology/ultrastructure ; Male ; Mesothelioma/*etiology/ultrastructure ; Microscopy, Electron ; Pleural Neoplasms/*etiology/ultrastructure ; Rats ; Rats, Inbred Strains ; Time Factors ; }, abstract = {Longitudinal light and electron microscopy investigations were previously carried out on Wistar rats to study the pathogenesis of pulmonary fibrosis due to asbestos. In the present study, the genesis of pulmonary carcinomas and pleural mesotheliomas have been investigated by light and electron microscopy on the same model after intrabronchial instillation of chrysotile B and benz(a)pyrene, as well as a combination of the two carcinogens. A single instillation of 1 mg chrysotile B with a fiber length between 0.05 and 0.2 micron in 0.1 ml tricaprylin by means of a polyvinyl catheter into the right lower lobe of the lung of 70 anesthetized 6-week-old Wistar rats caused pulmonary carcinomas or malignant pleural mesotheliomas in 18 animals (24%). The tumors occur at intervals between 12 and 31 months after the asbestos application. By electron microscopy, small asbestos fragments can be detected under the pleural mesothelium at the earliest 1 year after the intrabronchial application of chrysotile. A single combined instillation of 1 mg chrysotile and 0.5 mg benz(a)pyrene does not increase the tumor incidence. With simultaneous administration of these two substances, however, lung tumors arise very much earlier than in instillation of only one of the carcinogens. Thus, an adenocarcinoma was found in the lungs after 4.5 months, and a pleural mesothelioma was already found after 7.7 months. The intrabronchial instillation of benz(a)pyrene alone causes fewer lung tumors (tumor incidence 10%, interval between 13 and 33 months).}, } @article {pmid2839093, year = {1988}, author = {Minardi, F and Maltoni, C}, title = {Results of recent experimental research on the carcinogenicity of natural and modified asbestos.}, journal = {Annals of the New York Academy of Sciences}, volume = {534}, number = {}, pages = {754-761}, doi = {10.1111/j.1749-6632.1988.tb30164.x}, pmid = {2839093}, issn = {0077-8923}, mesh = {Administration, Inhalation ; Animals ; *Asbestos ; Asbestos, Serpentine ; Biological Assay ; Female ; Male ; Mesothelioma/etiology ; Mice ; Mutagenicity Tests ; Pleural Neoplasms/etiology ; Rats ; Rats, Inbred Strains ; }, abstract = {Long-term experimental bioassays were carried out on natural asbestos of different types and origin (crocidolite, chrysotile, amosite, antophyllite), on asbestos cement, and on industrially modified chrysotiles. The materials were tested on Sprague-Dawley rats by intraperitoneal and intrapleural injection. The experiments were carried out with highly standardized procedures on all materials to enable comparative evaluation of the results. The data presented confirm that asbestos of different types produces peritoneal and pleural mesotheliomas, show that asbestos cement is also mesotheliomatogenic, and demonstrate that the peritoneum is more responsive than the pleura. Furthermore, evidence is provided that the mesotheliomatogenic effects of different types of asbestos vary with the types and origin of the minerals, and that physical and chemical modifications of the natural chrysotile can lower its carcinogenic effect.}, } @article {pmid2839031, year = {1988}, author = {Mancuso, TF}, title = {Relative risk of mesothelioma among railroad machinists exposed to chrysotile.}, journal = {American journal of industrial medicine}, volume = {13}, number = {6}, pages = {639-657}, doi = {10.1002/ajim.4700130604}, pmid = {2839031}, issn = {0271-3586}, mesh = {Asbestos/*adverse effects ; Asbestos, Serpentine ; Epidemiologic Methods ; Humans ; Male ; Mesothelioma/*etiology/mortality ; Occupational Diseases/*etiology/mortality ; *Railroads ; Risk ; United States ; }, abstract = {This study challenges the assertion of low relative risk of chrysotile in the causation of mesothelioma. Data are provided on the time period use of various types of asbestos in the United States and in insulation materials. The focus of the study is on mesothelioma among railroad machinists employed in the steam locomotive era who were exposed to chrysotile. Within a cohort of machinists alive January 1, 1945, a sub-cohort method was applied to all successive machinists hired in each of the respective years (1920-1929) followed through 1986. The total cohort was 181 and the number of deaths 156, with 14 mesotheliomas identified among 41 cancer deaths. The findings demonstrated an extremely high relative risk for machinists exposed to chrysotile for the induction of mesothelioma in the individual year of hire cohorts. A similar observation was noted for other crafts hired in the same time period. One mesothelioma occurred for every 13 machinists hired in the succeeding years (1920-1929) and constituted 34% of all cancer deaths. It is concluded that chrysotile is far more hazardous in the induction of mesotheliomas and that the asbestos cancer risk in the steam locomotive eras was much higher than had been previously estimated.}, } @article {pmid2829959, year = {1988}, author = {Armstrong, BK and de Klerk, NH and Musk, AW and Hobbs, MS}, title = {Mortality in miners and millers of crocidolite in Western Australia.}, journal = {British journal of industrial medicine}, volume = {45}, number = {1}, pages = {5-13}, pmid = {2829959}, issn = {0007-1072}, mesh = {Adult ; Asbestos/adverse effects ; Asbestos, Crocidolite ; Asbestosis/*mortality ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; *Mining ; Pleural Neoplasms/mortality ; Western Australia ; }, abstract = {It is known that 6505 men and 411 women were employed in the mining and milling of crocidolite at Wittenoom in the Pilbara region of Western Australia between 1943 and 1966. Employment was usually brief (median duration four months) and exposure intense (median estimated cumulative exposure 6 fibres/cc years). The vital status of 73% of the men and 58% of the women employed in the industry was known at 31 December 1980, providing 95 264 person-years of follow up with 820 deaths in men and 4914 person-years with 23 deaths in women. The standardised mortality ratio (SMR) for all causes in men was 1.53 (95% confidence interval 1.43 to 1.64). Statistically significant excess death rates were observed in men for neoplasms, particularly malignant mesothelioma (32 deaths), neoplasms of the trachea, bronchus, and lung (SMR 2.64), and neoplasms of the stomach (SMR 1.90); respiratory diseases, particularly pneumoconiosis (SMR 25.5); infections, particularly tuberculosis (SMR 4.09); mental disorders particularly alcoholism (SMR 4.87); digestive diseases, particularly peptic ulceration (SMR 2.46) and cirrhosis of the liver (SMR 3.94); and injuries and poisonings, particularly non-transport accidents (SMR 2.36). The excess mortality from pneumoconiosis, malignant mesothelioma, and respiratory cancers, but not stomach neoplasms, was dependent on time since first exposure and cumulative exposure. There was no increase in mortality from laryngeal cancer (SMR 1.09) or neoplasms other than those listed. The SMR for all causes in women was 1.47 (95% confidence interval 0.98-2.21) and for neoplasms 1.99; there was one death from malignant pleural mesothelioma.}, } @article {pmid2458647, year = {1988}, author = {Henderson, DW and Attwood, HD and Constance, TJ and Shilkin, KB and Steele, RH}, title = {Lymphohistiocytoid mesothelioma: a rare lymphomatoid variant of predominantly sarcomatoid mesothelioma.}, journal = {Ultrastructural pathology}, volume = {12}, number = {4}, pages = {367-384}, doi = {10.3109/01913128809064207}, pmid = {2458647}, issn = {0191-3123}, mesh = {Aged ; Asbestos/adverse effects ; Diagnosis, Differential ; Environmental Exposure ; Humans ; Immunohistochemistry ; Lymphoma/immunology/*pathology/ultrastructure ; Male ; Mesothelioma/classification/immunology/*pathology/ultrastructure ; Microscopy, Electron ; Middle Aged ; Pleural Neoplasms/immunology/*pathology/ultrastructure ; Staining and Labeling ; T-Lymphocytes ; }, abstract = {Of 394 "definite" mesotheliomas entered in the Australian Mesothelioma Surveillance Program, three bore a striking resemblance to malignant lymphoma by conventional light microscopy, and each was misinterpreted at some stage as lymphoma. The lymphoma-like morphology was a combined result of intense lymphoplasmacytic infiltration and the histiocytoid appearances of the underlying neoplastic cell population. Immunocytochemical analysis demonstrated cytokeratins coexpressed with vimentin within the tumor cells, whereas immunoreactivity for leukocyte common antigen was confined to the smaller lymphoid cells. Electron microscopy of two cases revealed a polymorphous population of fibrohistiocytic cells resembling those typical of malignant fibrous histiocytoma, admixed with lymphocytes and plasma cells, but sporadic cells expressed mesothelial properties in the form of sinuous villiform processes, intracytoplasmic neolumina lined by microvilli, and intermediate filaments that were aggregated into tonofilament bundles in some cells. The ultrastructural appearances, the localization of the tumors to the pleura, with effusion, and absence of anterior mediastinal mass lesions facilitated exclusion of lymphocyte-rich thymoma. In addition, a history of prior occupational exposure to asbestos was elicited in each instance. There was no apparent response to radiotherapy or chemotherapy, and the patients died at 4, 5, and 8 months after presentation. Our observations suggest that immunocytochemical or ultrastructural evaluation is mandatory for accurate diagnosis of all pleura-based lymphomatoid lesions with a mixed large and small cell pattern.}, } @article {pmid3689066, year = {1987}, author = {Wolf, KM and Piotrowski, ZH and Engel, JD and Bekeris, LG and Palacios, E and Fisher, KA}, title = {Malignant mesothelioma with occupational and environmental asbestos exposure in an Illinois community hospital.}, journal = {Archives of internal medicine}, volume = {147}, number = {12}, pages = {2145-2149}, pmid = {3689066}, issn = {0003-9926}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Environmental Exposure ; Epidemiologic Methods ; Female ; *Hospitals, Community ; Humans ; Male ; Mesothelioma/*chemically induced/pathology ; Middle Aged ; Peritoneal Neoplasms/*chemically induced/pathology ; Pleural Neoplasms/*chemically induced/pathology ; }, abstract = {Clinical, radiologic, pathologic, and epidemiologic data on 32 patients with diffuse malignant mesothelioma (DMM) diagnosed between 1968 and 1984 at a 427-bed community hospital in Berwyn, Ill, were reviewed. Independent pathologists' review of light microscopy, supported by electron microscopy, immunoperoxidase staining, or autopsy, confirmed 29 pleural and three peritoneal DMMs. Clinical and radiologic characteristics were similar to those in published case series. Median age at diagnosis was 67 years, and median survival after diagnosis, seven months. Fourteen patients were women. Exposure histories were obtained through 22 interviews supplemented by hospital charts and death certificates. Thirty patients (94%) had a history of asbestos exposure through work (15 [47%]) and/or residence near an asbestos facility (27 [84%]). Medical records and death certificates underreported asbestos exposure and DMM.}, } @article {pmid3444934, year = {1987}, author = {Mauskopf, JA}, title = {Projections of cancer risks attributable to future exposure to asbestos.}, journal = {Risk analysis : an official publication of the Society for Risk Analysis}, volume = {7}, number = {4}, pages = {477-486}, doi = {10.1111/j.1539-6924.1987.tb00484.x}, pmid = {3444934}, issn = {0272-4332}, mesh = {Actuarial Analysis ; Asbestos/*adverse effects ; Humans ; Lung Neoplasms/*epidemiology ; Mesothelioma/*epidemiology ; Models, Theoretical ; Neoplasms/*epidemiology ; Occupational Diseases/*epidemiology ; Risk Factors ; United States ; }, abstract = {To assess the maximum possible impact of further government regulation of asbestos exposure, projections were made of the use of asbestos in nine product categories for the years 1985-2000. A life table risk assessment model was then developed to estimate the excess cases of cancer and lost person-years of life likely to occur among those occupationally and nonoccupationally exposed to the nine asbestos product categories manufactured in 1985-2000. These estimates were made under the assumption that government regulation remains at its 1985 level. Use of asbestos in the nine product categories was predicted to decline in all cases except for friction products. The risk assessment results show that, although the cancer risks from future exposure to asbestos are significantly less than those from past exposures, in the absence of more stringent regulations, a health risk remains.}, } @article {pmid3321468, year = {1987}, author = {Pendergrass, HP and Snell, JD and Carroll, FE}, title = {Diseases related to asbestos exposure: historical perspective.}, journal = {Southern medical journal}, volume = {80}, number = {12}, pages = {1546-1552}, doi = {10.1097/00007611-198712000-00015}, pmid = {3321468}, issn = {0038-4348}, mesh = {Asbestos/*adverse effects ; Asbestosis/*diagnostic imaging/history ; Carcinoma, Bronchogenic/etiology ; History, 20th Century ; Humans ; Lung Diseases, Obstructive/etiology ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Pleural Diseases/diagnostic imaging ; Pulmonary Emphysema/etiology ; Pulmonary Heart Disease/etiology ; Radiography ; }, abstract = {Our goal in this brief and limited historical summary of asbestos-related diseases has been to bring the clinician up to date with the current status of this important medical and public health issue. The references will provide an information source for those who require more comprehensive knowledge.}, } @article {pmid2827488, year = {1987}, author = {Craighead, JE and Akley, NJ and Gould, LB and Libbus, BL}, title = {Characteristics of tumors and tumor cells cultured from experimental asbestos-induced mesotheliomas in rats.}, journal = {The American journal of pathology}, volume = {129}, number = {3}, pages = {448-462}, pmid = {2827488}, issn = {0002-9440}, support = {1 R01 CA 36993/CA/NCI NIH HHS/United States ; }, mesh = {Abdominal Neoplasms/chemically induced/genetics/*pathology ; Animals ; Asbestos/*pharmacology ; Asbestos, Crocidolite ; Asbestos, Serpentine ; Cell Division ; Chromosomes/ultrastructure ; Female ; Mesothelioma/chemically induced/genetics/*pathology ; Microscopy, Electron ; Microscopy, Electron, Scanning ; Neoplasms, Experimental/chemically induced ; Rats ; Rats, Inbred F344 ; Tumor Cells, Cultured ; }, abstract = {Mesotheliomas developed in rats in the abdominal cavity 6-23 months after peritoneal introduction of chrysotile and crocidolite asbestos. The tumors were strikingly similar to those occurring in man both with regard to histologic features and growth patterns. The authors have cultured cells from these tumors and established epithelial lines with a variety of karyologic features and doubling times shorter than those of normal mesothelial cells. Lines of diploid or near-diploid tumor cells required serum in the medium to replicate, whereas most aneuploid cell lines were maintained in a serum-free medium. In serum-free medium, the aneuploid line monolayers produced anchorage-independent excrescent masses of cells which "bud" and float free. These spheroids, which strikingly resemble the papillary structures in human mesotheliomas, are composed of mesothelial-like cells that produce hyaluronic acid and have a rich complement of intermediate filaments, predominantly cytokeratins. Aneuploid cells also replicated in soft agar with high efficiency, whereas the diploid and near-diploid cells did not. All but one cultured cell line, regardless of karyotype, produced tumors after subcutaneous or intraperitoneal inoculation (or both). Aneuploid cells caused lung tumors sporadically when introduced intravenously. Comparative analysis of the nuclear DNA of primary tumors and cultured cells demonstrated a high degree of chromosomal instability and selection among cells during early passage in vitro.}, } @article {pmid3689712, year = {1987}, author = {Ho, SF and Lee, HP and Phoon, WH}, title = {Malignant mesothelioma in Singapore.}, journal = {British journal of industrial medicine}, volume = {44}, number = {11}, pages = {788-789}, pmid = {3689712}, issn = {0007-1072}, mesh = {Adult ; Asbestos/adverse effects ; Humans ; Male ; Mesothelioma/*etiology ; Middle Aged ; Neoplasms/*etiology ; Occupational Diseases/*etiology ; Peritoneal Neoplasms/etiology ; Pleural Neoplasms/etiology ; Singapore ; }, } @article {pmid2959164, year = {1987}, author = {Schwartz, E and Landrigan, P}, title = {Use of court records for supplementing occupational disease surveillance.}, journal = {American journal of public health}, volume = {77}, number = {11}, pages = {1457-1458}, pmid = {2959164}, issn = {0090-0036}, mesh = {Asbestosis/*epidemiology/mortality ; Death Certificates ; Epidemiologic Methods ; Humans ; Jurisprudence ; Mesothelioma/*epidemiology/mortality ; New Hampshire ; Occupational Diseases/*epidemiology/mortality ; Workers' Compensation ; }, abstract = {To conduct surveillance of occupationally related health events, the New Hampshire Division of Public Health Services analyzes death certificates and workers' compensation claims. In an effort to bolster these limited data sources, a previously unrecognized data-set comprised of court records was explored. Court records obtained from the Federal District Court proved to be a readily accessible and detailed source of information for identifying suspected cases of asbestos-related disease and potential sources of asbestos exposure.}, } @article {pmid2443239, year = {1987}, author = {Mackay, AM and Tracy, RP and Craighead, JE}, title = {Intermediate filament proteins in asbestos-induced mesotheliomas of the rat.}, journal = {Cancer research}, volume = {47}, number = {20}, pages = {5461-5468}, pmid = {2443239}, issn = {0008-5472}, support = {R01-36993//PHS HHS/United States ; R23-40936//PHS HHS/United States ; }, mesh = {Animals ; *Asbestos ; Asbestos, Serpentine ; Electrophoresis, Polyacrylamide Gel ; Female ; Immunosorbent Techniques ; Intermediate Filament Proteins/*analysis ; Keratins/analysis ; Mesothelioma/analysis/*etiology ; Molecular Weight ; Peritoneal Neoplasms/analysis/*etiology ; Rats ; Rats, Inbred F344 ; Vimentin/analysis ; }, abstract = {Abdominal diffuse malignant mesotheliomas develop in rats administered asbestos by the intraperitoneal route. A latency period of 6 to 24 months precedes tumor development; the biological and morphological features of these tumors resemble mesotheliomas in humans. Using one- and two-dimensional gel electrophoresis and immunoblotting, rat mesotheliomas (n = 24) were shown to express two classes of intermediate filament (IF) proteins. The tumors contained both vimentin and at least one of six keratins (p40, Mr 40,000; Dm, Mr 50,000; p53, Mr 53,000; Bm, Mr 53,000; Cm, Mr 54,000; Am, Mr 54,000). Vimentin predominated in 15 of 16 tumors exhibiting either sarcomatous or mixed (epithelial and mesenchymal) appearance. One of eight mixed lesions and six of eight epithelial tumors had a complement of IF proteins in which cytokeratins predominated. A similar pattern has been reported in mesotheliomas in humans (Blobel et al., Am. J. Pathol. 121: 235, 1985). Epithelial tumors often contain comparable amounts of vimentin and low molecular weight cytokeratins, while vimentin is the most actively expressed IF protein in sarcomatous tumors. Thus, tumors induced by asbestos in the rat peritoneum express IF proteins in a manner that resembles human mesotheliomas, supporting the notion that these lesions are appropriate models of human mesothelioma.}, } @article {pmid3676121, year = {1987}, author = {Kogan, FM and Vanchugova, NN and Frasch, VN}, title = {Possibility of inducing glandular stomach cancer in rats exposed to asbestos.}, journal = {British journal of industrial medicine}, volume = {44}, number = {10}, pages = {682-686}, pmid = {3676121}, issn = {0007-1072}, mesh = {Abdominal Neoplasms/etiology ; Adenocarcinoma/etiology ; Adenoma/etiology ; Animals ; Asbestos/*toxicity ; Carcinosarcoma/etiology ; Intestinal Neoplasms/etiology ; Mesothelioma/etiology ; Rats ; Stomach Neoplasms/*etiology ; }, abstract = {The possibility of glandular stomach cancer being induced was studied in 75 random bred white rats exposed to chrysotile asbestos. A perforated polyethylene capsule containing 100 mg asbestos and filler (beef fat and natural wax mixture 1:1) was introduced in an artificial bag placed on the greater curvature of the stomach. A capsule containing filler only was introduced in a similar way in 40 control rats. In the following 25 months, 18 tumors of the stomach and abdominal cavity were found in the rats treated with asbestos (eight adenomas, two adenocarcinomas, one carcinosarcoma, one forestomach cancer, one intestinal adenocarcinoma, two peritoneal mesotheliomas, and three abdominal lymphoreticulosarcomas.) Among the control rats no such tumors were found. The results of the experiment are discussed in connection with epidemiological data on stomach cancer in asbestos workers.}, } @article {pmid2821313, year = {1987}, author = {Jaurand, MC and Fleury, J and Monchaux, G and Nebut, M and Bignon, J}, title = {Pleural carcinogenic potency of mineral fibers (asbestos, attapulgite) and their cytotoxicity on cultured cells.}, journal = {Journal of the National Cancer Institute}, volume = {79}, number = {4}, pages = {797-804}, pmid = {2821313}, issn = {0027-8874}, mesh = {Animals ; *Asbestos ; Asbestos, Serpentine ; Cell Survival/drug effects ; Cells, Cultured ; Macrophages/metabolism ; *Magnesium ; *Magnesium Compounds ; Male ; Mesothelioma/etiology ; Particle Size ; Pleural Neoplasms/*etiology ; Pulmonary Alveoli/pathology ; Rats ; Rats, Inbred Strains ; *Silicon ; *Silicon Compounds ; }, abstract = {The carcinogenicity of several samples of mineral fibers was tested following injection of 20 mg in the pleural cavity of noninbred Sprague-Dawley rats. Three samples of chrysotile asbestos (mean length: 3.2, 2.1, and 1.2 micron) induced mesotheliomas at a rate of 48, 52, and 19%, respectively. The first sample was acid leached prior to intrapleural injection; in that group, the percentage of mesotheliomas was reduced to 25%. Treatment with amosite and crocidolite resulted in the occurrence of 57 and 56% of mesotheliomas. Acid-treatment of amphiboles did not significantly modify the percentage of mesotheliomas. When the Stanton's fiber dimensions were taken into consideration to correlate with mesothelioma incidence, the observed number of mesotheliomas in the chrysotile-treated animals was much lower than that expected, suggesting that other fiber parameters (chemistry, physicochemistry) play a role in the carcinogenicity. Attapulgite fibers (mean length: 0.77 micron) did not induce tumor, and the mean survival time was of the same order as that observed in the control groups. The injection of quartz resulted in no mesothelioma but did result in 6 malignant histiocytic lymphomas (17%) and 2 malignant schwannomas (6%). In vitro experiments did not show strong correlation between cytotoxicity and the carcinogenic potency of these minerals, but the qualitative cellular responses might give some indications on the fiber's potency. In addition, the in vitro effects of the fibers seem to be modulated by their size.}, } @article {pmid3499174, year = {1987}, author = {Hilt, B}, title = {Non-malignant asbestos diseases in workers in an electrochemical plant.}, journal = {British journal of industrial medicine}, volume = {44}, number = {9}, pages = {621-626}, pmid = {3499174}, issn = {0007-1072}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestosis/diagnostic imaging/*epidemiology ; *Chemical Industry ; Cross-Sectional Studies ; Humans ; Male ; Middle Aged ; Norway ; Radiography ; Smoking/adverse effects ; }, abstract = {The prevalence of non-malignant asbestos related disorders was studied in a group of men who had been subjected to different levels of asbestos exposure when working at an electrochemical plant producing nitric acid sometime between 1928 and 1970. There were 153 men eligible for an initial clinical examination in 1979-80 and that group has been followed up to 1985. Among the cohort members the "accumulated prevalence" of lung fibrosis alone or in combination with pleural plaques and of "pleural plaques only" was 24.2% and 24.8% respectively. The subgroup with the heaviest exposure had a total prevalence of asbestos related disorders of 82.5%. Only study subjects with lung fibrosis had statistically significant increased prevalences of respiratory symptoms. All subgroups from the study population, however, had mean spirometric values under the age, height, and smoking specific predicted means. Subjects with heavy asbestos exposure and current smoking had a prevalence of three or more respiratory symptoms of 28.8% compared with 5.6% among lightly exposed never smokers. Pleural crepitations at chest auscultation were more prevalent among subjects with radiologically visible asbestos related disorders than among study subjects with normal chest x ray films. During the follow up from 1980 to 1985, three cases of lung cancer, two of pleural malignant mesothelioma, and one of stomach cancer were found among the cohort members.}, } @article {pmid2820232, year = {1987}, author = {Moalli, PA and MacDonald, JL and Goodglick, LA and Kane, AB}, title = {Acute injury and regeneration of the mesothelium in response to asbestos fibers.}, journal = {The American journal of pathology}, volume = {128}, number = {3}, pages = {426-445}, pmid = {2820232}, issn = {0002-9440}, support = {KO4 ES 00127/ES/NIEHS NIH HHS/United States ; R01 ES 03189/ES/NIEHS NIH HHS/United States ; R01 ES 03721/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Asbestos/analysis/*toxicity ; Asbestos, Crocidolite ; Diaphragm/pathology ; Epithelium/analysis/pathology ; Inflammation/etiology ; Lymphatic System/pathology ; Male ; Mesothelioma/*etiology/pathology ; Mice ; Mice, Inbred C57BL ; Microscopy, Electron, Scanning ; Microvilli/pathology ; Peritoneal Cavity/pathology ; Silicon Dioxide/toxicity ; }, abstract = {The mesothelium is a target of the toxic and carcinogenic effects of asbestos fibers. Fibers greater than 8 mu in length and less than 0.25 mu in diameter have been found to be highly tumorigenic in rodents, while shorter asbestos fibers or spherical mineral particles have not been shown to produce mesotheliomas. For investigation of early mesothelial reactions associated with the development of mesotheliomas, C57BL/6 mice were given intraperitoneal injections of 200 micrograms of short or long crocidolite asbestos fibers, toxic silica particles, or nontoxic titanium dioxide particles. At intervals between 3 hours and 21 days after a single injection, the mesothelial surface of the diaphragm was examined by stereomicroscopy, scanning electron microscopy, and autoradiography. Within 6 hours after injection of asbestos fibers, mesothelial cells in the lacunar regions of the diaphragm retracted opening stomata 10.7 +/- 2.3 mu in diameter leading to the submesothelial lymphatic plexus. Short asbestos fibers (90.6% less than or equal to 2 mu in length), silica, or titanium dioxide particles (less than or equal to 5 mu in diameter) were cleared through these stomata without provoking an inflammatory reaction or mesothelial injury. In contrast, long asbestos fibers (60.3% greater than or equal to 2 mu in length) were trapped at the lymphatic stomata in the lacunar regions on the peritoneal surface of the diaphragm. At these sites, an intense inflammatory reaction developed with accumulation of activated macrophages and a 5.5-fold increase in albumin recovered in the peritoneal lavage fluid after 3 days. As early as 12 hours after injection of long asbestos fibers, the adjacent mesothelial cells were unable to exclude trypan blue and lost their surface microvilli, developed blebs, and detached. Recovery of lactate dehydrogenase activity in the peritoneal lavage fluid was increased 5.8-fold after 3 days and returned to normal levels after 14 days. Regenerating mesothelial cells appeared at the periphery of asbestos fiber clusters 3 days after injection. Maximal incorporation of 3H-thymidine by mesothelial cells occurred after 7 days, followed by partial restoration of the mesothelial lining after 14-21 days. As late as 6 months after a single injection of crocidolite asbestos fibers, clusters of fibers remained in the lacunar regions, partially covered by mesothelium but surrounded by macrophages and regenerating mesothelial cells. The anatomic distribution and size of lymphatic stomata on the peritoneal surface of the diaphragm account for the selective accumulation of long asbestos fibers in these regions.(ABSTRACT TRUNCATED AT 400 WORDS)}, } @article {pmid3657627, year = {1987}, author = {Ferguson, DA and Berry, G and Jelihovsky, T and Andreas, SB and Rogers, AJ and Fung, SC and Grimwood, A and Thompson, R}, title = {The Australian Mesothelioma Surveillance Program 1979-1985.}, journal = {The Medical journal of Australia}, volume = {147}, number = {4}, pages = {166-172}, doi = {10.5694/j.1326-5377.1987.tb133348.x}, pmid = {3657627}, issn = {0025-729X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Australia ; Female ; Humans ; Lung Neoplasms/*epidemiology/etiology ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Diseases/*epidemiology/etiology ; Registries ; }, abstract = {The Australian Mesothelioma Surveillance Program was planned in 1977 in order to improve diagnostic criteria, to monitor the incidence of the disease, to develop methods of counting lung fibres, and to explore occupational and other associations of mesothelioma. This paper presents a preliminary analysis of data that were collected between January 1, 1980 and December 31, 1985 on the pathological findings and the work and environmental history of 858 cases of mesothelioma. The annual incidence rate of mesothelioma in Australia was 15 per million population who were aged 20 years and over. This is more than the incidence rate of mesothelioma in any other country for which data are available. However, uncertainty over diagnostic criteria and the degree of ascertainment of cases places doubt on the validity of such comparisons. In 69% of cases, a history of work with or other exposure to asbestos was obtained. Due to the long interval between the first exposure to asbestos and the provisional diagnosis of a mesothelioma (up to 60 years), more than three-quarters of the 456 exposed cases first contacted asbestos in the years of its heavy use between 1930 and 1959. This article analyses cases by the industry and the occupation in which exposure to asbestos first occurred.}, } @article {pmid3657624, year = {1987}, author = {Rossiter, CE}, title = {Asbestos blues.}, journal = {The Medical journal of Australia}, volume = {147}, number = {4}, pages = {162-163}, doi = {10.5694/j.1326-5377.1987.tb133345.x}, pmid = {3657624}, issn = {0025-729X}, mesh = {Asbestos/*adverse effects ; Australia ; Humans ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Occupational Diseases/etiology ; }, } @article {pmid3594370, year = {1987}, author = {Suzuki, Y and Chahinian, AP and Ohnuma, T}, title = {Comparative studies of human malignant mesothelioma in vivo, in xenografts in nude mice, and in vitro. Cell origin of malignant mesothelioma.}, journal = {Cancer}, volume = {60}, number = {3}, pages = {334-344}, doi = {10.1002/1097-0142(19870801)60:3<334::aid-cncr2820600310>3.0.co;2-#}, pmid = {3594370}, issn = {0008-543X}, support = {CA36283/CA/NCI NIH HHS/United States ; ES00928/ES/NIEHS NIH HHS/United States ; }, mesh = {Aged ; Animals ; Antigens, Neoplasm/analysis ; Asbestos ; Cell Differentiation ; Cell Line ; Female ; Histocytochemistry ; Humans ; Male ; Mesothelioma/*pathology ; Mice ; Mice, Nude ; Microscopy, Electron ; Middle Aged ; }, abstract = {Several decades ago, it was reported that normal and malignant mesothelial cells were transformed into distinct cell types (epithelial to fibrous and fibrous to epithelial) when transferred to in vitro conditions. Those tissue culture data are still cited as evidence supporting that the mesothelial cell has multipotentiality of differentiation and the mesothelial cell is a sole precursor of malignant mesothelioma cells. Six cell lines of heterotransplanted human malignant mesothelioma in nude mice and one cell line of subcultured human malignant mesothelioma in vitro have been established. To establish the validity of the classic concept of multipotentiality of malignant mesothelioma, we studied malignant mesothelioma cells of the seven cases using in vivo cultures, xenografts in nude mice and an in vitro tissue culture, utilizing histology, histochemistry, immunocytochemistry and electron microscopy. The nature of the original malignant mesothelioma cells was clearly shown to be well preserved in both the heterotransplanted and subcultured cells. Data did not support earlier hypotheses that mesothelial cells are capable of differentiating into distinct cell lines. The mesothelial cell and the submesothelial connective tissue cells are the precursors of the neoplastic cells in malignant mesothelioma.}, } @article {pmid3694954, year = {1987}, author = {Kishimoto, T and Okada, K and Sato, T and Ono, T and Ito, H}, title = {[Evaluation of the relation between pleural malignant mesothelioma and asbestos exposure].}, journal = {Nihon Kyobu Shikkan Gakkai zasshi}, volume = {25}, number = {7}, pages = {752-756}, pmid = {3694954}, issn = {0301-1542}, mesh = {Aged ; Asbestos/*adverse effects ; Environmental Exposure ; Female ; Humans ; Lung/pathology ; Male ; Mesothelioma/*etiology/pathology ; Middle Aged ; Pleural Neoplasms/*etiology/pathology ; }, } @article {pmid3683276, year = {1987}, author = {Paci, E and Buiatti, E and Zappa, M and Di Natale, M and Vannucchi, G and Dini, S and Biancalani, M}, title = {[Asbestos pollution in the Prato textile cycle: epidemiologic evidence].}, journal = {La Medicina del lavoro}, volume = {78}, number = {4}, pages = {283-292}, pmid = {3683276}, issn = {0025-7818}, mesh = {Adult ; Aged ; Air Pollutants, Occupational/analysis ; Asbestos/*adverse effects ; Female ; Humans ; Italy ; Lung Neoplasms/*epidemiology/etiology ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Diseases/*epidemiology/etiology ; Occupations ; *Textile Industry ; }, } @article {pmid3474447, year = {1987}, author = {Enterline, PE and Henderson, VL}, title = {Geographic patterns for pleural mesothelioma deaths in the United States, 1968-81.}, journal = {Journal of the National Cancer Institute}, volume = {79}, number = {1}, pages = {31-37}, pmid = {3474447}, issn = {0027-8874}, mesh = {Age Factors ; Aged ; Asbestos/adverse effects ; Demography ; Female ; Humans ; Male ; Mesothelioma/etiology/*mortality ; Middle Aged ; Pleural Neoplasms/etiology/*mortality ; Sex Factors ; Ships ; United States ; }, abstract = {Deaths and death rates for mesothelioma of the pleura are presented by age, sex, and geographic area for the United States for the years 1968-81. Death rates increased with age and in every age group were roughly three times higher for males than for females. Over the period 1968-81, death rates increased for males aged 65 years or more, whereas death rates in other age-sex groupings remained fairly constant or declined slightly. It is known that asbestos is highly related to mesothelioma, and the increase in death rates among older males could be due to asbestos. Conversely, the fact that death rates in younger males and in females have not been increasing suggests some kind of background level not strongly related to the use of asbestos. When the geographic distribution of death rates was examined by state, there was considerable geographic variation with some clustering. High death rates for males appeared for the Northeastern States and along the Pacific Coast, and for Illinois, Florida, Wyoming, and Colorado. Females shared this geographic pattern to some extent. When death rates were examined by county, a relationship was seen between pleural mesothelioma deaths among males and the presence of asbestos products plants and shipbuilding facilities. Excessive death rates in some counties and states did not appear to be related to asbestos exposure. Although the similarity in geographic patterns of mortality for males and females suggests a common etiology, the trends in mortality suggest different etiologies. There may be important causes of pleural mesothelioma yet to be identified.}, } @article {pmid3606969, year = {1987}, author = {Lilis, R and Ribak, J and Suzuki, Y and Penner, L and Bernstein, N and Selikoff, IJ}, title = {Non-malignant chest x ray changes in patients with mesothelioma in a large cohort of asbestos insulation workers.}, journal = {British journal of industrial medicine}, volume = {44}, number = {6}, pages = {402-406}, pmid = {3606969}, issn = {0007-1072}, mesh = {Asbestos/*adverse effects ; Fibrosis ; Humans ; Mesothelioma/*diagnostic imaging/etiology ; Occupational Diseases/*diagnostic imaging/etiology ; Peritoneal Neoplasms/*diagnostic imaging/etiology ; Peritoneum/diagnostic imaging/pathology ; Pleura/diagnostic imaging/pathology ; Pleural Neoplasms/*diagnostic imaging/etiology ; Precancerous Conditions/*diagnostic imaging ; Pulmonary Fibrosis/diagnostic imaging/etiology ; Radiography ; }, abstract = {To assess the prevalence of non-malignant chest x ray abnormalities in cases of mesothelioma 184 cases of mesothelioma (72 pleural and 112 peritoneal) which had occurred in a cohort of asbestos insulation workers followed up since 1967 were studied. Chest x ray films of satisfactory quality, on which the presence or absence of non-malignant radiological changes indicating interstitial pulmonary fibrosis or pleural fibrosis or both, could be assessed with a high degree of certainty were available. In some cases (20% for pleural mesothelioma, 11.6% for peritoneal mesothelioma) non-malignant radiological changes were not radiologically detectable. Parenchymal interstitial fibrosis (small irregular opacities) only was found in a proportion of cases (25.4% of pleural mesotheliomas, 12.5% of peritoneal mesotheliomas). Pleural fibrosis only was detected in 17% of cases of pleural mesothelioma and 27% of cases of peritoneal mesothelioma. Most patients had both parenchymal and pleural fibrosis. Although these results tend to indicate that in peritoneal mesothelioma the proportion of pleural fibrosis is significantly higher, these findings might have been due to the fact that in most cases of pleural mesothelioma non-malignant changes were interpreted in one hemithorax only. In 46 cases (21 pleural, 25 peritoneal) in which sufficient lung tissue was available histopathology of lung parenchyma indicated the presence of interstitial fibrosis; in 20 (43.5%) of these the chest x ray film had been read as negative. Thus the absence of radiologically detectable small opacities on the chest x ray film does not exclude the existence of interstitial pulmonary fibrosis in cases of mesothelioma among insulation workers. With lower levels of exposure (such as in family contacts of asbestos workers) it is conceivable that mesothelioma might occur in the absence of interstitial pulmonary fibrosis.}, } @article {pmid3606968, year = {1987}, author = {Enterline, PE and Hartley, J and Henderson, V}, title = {Asbestos and cancer: a cohort followed up to death.}, journal = {British journal of industrial medicine}, volume = {44}, number = {6}, pages = {396-401}, pmid = {3606968}, issn = {0007-1072}, mesh = {Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Follow-Up Studies ; Humans ; Male ; Mesothelioma/etiology/mortality ; Middle Aged ; Neoplasms/etiology/*mortality ; Occupational Diseases/etiology/*mortality ; Peritoneal Neoplasms/etiology/mortality ; Pleural Neoplasms/etiology/mortality ; Respiratory Tract Neoplasms/etiology/mortality ; Risk ; United States ; }, abstract = {The mortality experience of 1074 white men who retired from a United States asbestos company during the period 1941-67 and who were exposed to asbestos working as production and maintenance employees for the company is reported to the end of 1980 when 88% of this cohort was known to be dead. As noted in earlier reports the mortality for respiratory and gastrointestinal cancer was raised. A more detailed examination of causes of death shows that the excess in gastrointestinal cancer was largely due to a statistically significant excess in stomach cancer. A statistically significant excess was also noted for kidney cancer, cancer of the eye, and non-malignant respiratory disease. Eight deaths from malignant mesothelioma were observed, two of which were peritoneal. Asbestos exposures for these mesothelioma cases were low relative to other members of the cohort. Continuing follow up of this cohort shows a dose response relation for respiratory cancer that has become increasingly linear. Standardised mortality ratios peaked 10 to 15 years after retirement and were relatively constant at around 250 in each five year interval starting in 1950. This excess might have been detected as early as 1960 but certainly by 1965. The mortality experience of this cohort reflects the ultimate effects of asbestos since nearly all of the cohort has now died.}, } @article {pmid3473246, year = {1987}, author = {Connelly, RR and Spirtas, R and Myers, MH and Percy, CL and Fraumeni, JF}, title = {Demographic patterns for mesothelioma in the United States.}, journal = {Journal of the National Cancer Institute}, volume = {78}, number = {6}, pages = {1053-1060}, pmid = {3473246}, issn = {0027-8874}, mesh = {Adolescent ; Adult ; Aged ; Female ; Humans ; Male ; Mesothelioma/*epidemiology/mortality ; Middle Aged ; Peritoneal Neoplasms/*epidemiology/mortality ; Pleural Neoplasms/*epidemiology ; Sex Factors ; Time Factors ; United States ; }, abstract = {Incidence rates for pleural and peritoneal mesotheliomas in about 10% of the U.S. population were examined by various demographic characteristics based on 1973-84 data from the Surveillance, Epidemiology, and End Results Program. Although pleural mesothelioma was more common than peritoneal mesothelioma, both are rare diseases in this country. Pleural mesothelioma incidence rates among white males increased over time and were highest in seaboard areas where shipyards have been located (Seattle, San Francisco-Oakland, Hawaii). The significant secular change was attributed to both period (date of diagnosis) and cohort (date of birth) effects. Pleural mesothelioma incidence rates among white males were nearly 50% higher in the 1980-84 period compared to those in 1975-79; the cohort effect rose to a peak for the 1905-9 birth cohort and then declined. These effects probably reflect changes in asbestos exposure patterns in the past and more recent changes in clinical awareness and coding rules for mesothelioma. Geographic analysis of U.S. death certificates for pleural cancer among white males and females dying during 1968-78 indicated that mortality rates were significantly elevated in several areas that have had asbestos-manufacturing plants or shipyards. Analyses of mortality rates must be viewed with caution, since mesothelioma is considerably underreported on death certificates.}, } @article {pmid3036684, year = {1987}, author = {Craighead, JE}, title = {Current pathogenetic concepts of diffuse malignant mesothelioma.}, journal = {Human pathology}, volume = {18}, number = {6}, pages = {544-557}, doi = {10.1016/s0046-8177(87)80354-4}, pmid = {3036684}, issn = {0046-8177}, mesh = {Animals ; Asbestos/metabolism ; Asbestos, Amphibole ; Asbestos, Serpentine ; Epidemiologic Methods ; Foreign Bodies/complications ; Humans ; Mesothelioma/*chemically induced/pathology ; Neoplasms, Experimental/etiology ; Neoplastic Stem Cells/pathology ; Peritoneal Neoplasms/chemically induced ; Pleural Neoplasms/*chemically induced/pathology ; Precancerous Conditions/chemically induced ; Silicon Dioxide ; }, } @article {pmid3035848, year = {1987}, author = {Topov, J and Kolev, K}, title = {Cytology of experimental mesotheliomas induced with crocidolite asbestos.}, journal = {Acta cytologica}, volume = {31}, number = {3}, pages = {369-373}, pmid = {3035848}, issn = {0001-5547}, mesh = {Animals ; Asbestos/*adverse effects ; Asbestos, Crocidolite ; Ascitic Fluid/cytology/pathology ; Cell Nucleus/analysis ; Cell Transformation, Neoplastic ; Female ; Histocytochemistry ; Mesothelioma/*chemically induced/pathology ; Mitosis/drug effects ; Neoplasms, Experimental/*chemically induced/pathology ; Pleural Effusion/pathology ; Rats ; Rats, Inbred Strains ; }, abstract = {The cellular features of 12 pleural and 5 peritoneal effusions, derived from experimental mesotheliomas induced with crocidolite asbestos in white rats, are described. The fluids were obtained 11 to 18 months after the introduction of asbestos into the body cavity. The morphologic characteristics of the cytoplasm, nuclei and nucleoli in the neoplastic mesothelial cells were studied using the Pappenheim, periodic acid-Schiff and Smetana stains. Nearly all effusions examined contained numerous normal and abnormal mitoses. Cell configurations suggestive of amitotic divisions were also observed. The study of the morphologic features of mesothelial cells in effusions in experimental asbestos-induced mesotheliomas may contribute to the understanding of the neoplastic transformation of the mesothelium.}, } @article {pmid2821642, year = {1987}, author = {McConnochie, K and Simonato, L and Mavrides, P and Christofides, P and Pooley, FD and Wagner, JC}, title = {Mesothelioma in Cyprus: the role of tremolite.}, journal = {Thorax}, volume = {42}, number = {5}, pages = {342-347}, pmid = {2821642}, issn = {0040-6376}, mesh = {Aged ; *Asbestos, Amphibole ; Cyprus ; Dust/analysis ; Female ; Humans ; Lung/analysis ; Lung Neoplasms/*etiology ; Male ; Mesothelioma/*etiology ; Middle Aged ; Silicic Acid/*adverse effects/analysis ; Silicon Dioxide/*adverse effects ; }, abstract = {There is a chrysotile mine in the central mountains of Cyprus but no other appreciable source of industrial asbestos. Hence the island was thought to offer ideal conditions to seek pure chrysotile induced mesothelioma. The first reported case was a village woman whose lung tissue contained amphibole asbestos fibres, which were later identified as tremolite. This began a search for the origin of her exposure to asbestos. Our studies have shown that tremolite is widespread, being found, along with chrysotile, in domestic and environmental dust samples. Other cases of mesothelioma have been diagnosed, and the pattern of their distribution suggests that the mine is not the major source of disease. Exposure to tremolite is equally, if not more, important.}, } @article {pmid2882352, year = {1987}, author = {Langer, AM and Nolan, RP and Constantopoulos, SH and Moutsopoulos, HM}, title = {Association of Metsovo lung and pleural mesothelioma with exposure to tremolite-containing whitewash.}, journal = {Lancet (London, England)}, volume = {1}, number = {8539}, pages = {965-967}, doi = {10.1016/s0140-6736(87)90305-9}, pmid = {2882352}, issn = {0140-6736}, support = {ES 00928/ES/NIEHS NIH HHS/United States ; OH 01905/OH/NIOSH CDC HHS/United States ; }, mesh = {Adult ; Aged ; *Asbestos, Amphibole ; Calcinosis/epidemiology/*etiology ; Environmental Exposure ; Female ; Greece ; Humans ; Lung Diseases/epidemiology/*etiology ; Male ; Mesothelioma/epidemiology/*etiology ; Middle Aged ; Paint/analysis ; Pleural Neoplasms/epidemiology/*etiology ; Silicic Acid/*adverse effects/analysis ; Silicon Dioxide/*adverse effects ; X-Ray Diffraction ; }, abstract = {Pleural thickening, bilateral pleural hyalinised plaques, and restrictive lung function are found among inhabitants of four small villages in northwestern Greece. Transbronchial biopsy samples from patients with disease contained tremolite fibres. Malignant pleural mesothelioma has now been reported in these villages and accounts for approximately 1% of the total mortality from 1981 to 1985. The principal whitewash once used in this area is predominantly asbestiform tremolite. The fibre is identical in every respect to fibres found in the lung tissues of people with Metsovo lung. The membrane activity of this tremolite is greater than that of the commercially used asbestiform amphiboles amosite and crocidolite. This measure of cytotoxicity lends further support to the hypothesis that this fibre is the agent of Metsovo lung and mesothelioma.}, } @article {pmid3611919, year = {1987}, author = {Kishimoto, T and Ono, T and Okada, K}, title = {[Evaluation of 15 malignant mesothelioma patients from the aspect of clinical findings and pathology--relationship between asbestos and malignant mesothelioma].}, journal = {Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine}, volume = {76}, number = {4}, pages = {586-587}, doi = {10.2169/naika.76.586}, pmid = {3611919}, issn = {0021-5384}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Female ; Humans ; Male ; Mesothelioma/*etiology/pathology ; Middle Aged ; Occupational Diseases/*etiology/pathology ; Peritoneal Neoplasms/*etiology/pathology ; Pleural Neoplasms/*etiology/pathology ; }, } @article {pmid3565948, year = {1987}, author = {Huncharek, M}, title = {Asbestos-related mesothelioma risk among railroad workers.}, journal = {The American review of respiratory disease}, volume = {135}, number = {4}, pages = {983-984}, doi = {10.1164/arrd.1987.135.4.983b}, pmid = {3565948}, issn = {0003-0805}, mesh = {Asbestos/*adverse effects ; Female ; Humans ; Male ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; Pleural Neoplasms/*etiology ; *Railroads ; Risk ; }, } @article {pmid3303386, year = {1987}, author = {Rosenstock, L and Hudson, LD}, title = {The pleural manifestations of asbestos exposure.}, journal = {Occupational medicine (Philadelphia, Pa.)}, volume = {2}, number = {2}, pages = {383-407}, pmid = {3303386}, issn = {0885-114X}, mesh = {Asbestosis/*pathology ; Diagnosis, Differential ; Humans ; Mesothelioma/pathology ; Pleura/pathology ; Pleural Diseases/*pathology ; Pleural Neoplasms/pathology ; Tomography, X-Ray Computed ; }, abstract = {Pleural abnormalities are the most common disease manifestations of asbestos exposure and have both clinical and epidemiologic implications. Benign pleural processes include pleural thickening, which can be discrete (plaques) or diffuse, rounded atelectasis (pseudotumor), and benign exudative asbestos effusions. Asbestos is the most significant cause of diffuse malignant mesothelioma. Most patients with discrete pleural thickening have normal pulmonary function. Patients with extensive pleural involvement, however, can have significant restrictive impairment with no or only minimal interstitial disease. For any given radiological grade of parenchymal disease, pulmonary function is more impaired when pleural thickening is present. The presence of typical pleural changes can serve as a reliable marker for asbestos exposure in epidemiologic studies. Individuals with pleural plaques are more likely to develop parenchymal involvement than similarly exposed workers without pleural disease. Once present, pleural changes are likely to progress even in the absence of further exposure.}, } @article {pmid3032602, year = {1987}, author = {Keast, D and Sheppard, NP and Papadimitriou, JM}, title = {Some biological properties of respirable iron ore dust.}, journal = {Environmental research}, volume = {42}, number = {2}, pages = {455-468}, doi = {10.1016/s0013-9351(87)80213-x}, pmid = {3032602}, issn = {0013-9351}, mesh = {Animals ; Asbestos/toxicity ; Asbestos, Crocidolite ; Dust/*adverse effects ; Female ; Iron/*toxicity ; Leukemia, Experimental/etiology ; Lung/pathology ; Mice ; Mice, Inbred C57BL ; Neoplasms, Experimental/etiology ; Rats ; Rats, Inbred Strains ; }, abstract = {The respirable fraction of an ore dust from the North-West of Western Australia was tested for biological properties by inhalation and intrapleural implantation trials using rats and mice. Pulmonary histology indicated significant levels of interstitial pneumonia occasionally associated with bronchopneumonia, bronchiectasis, emphysema, and lung collapse over that found in age-matched control animals. While there was a significant increase of the incidence of tumors in general in WAG inbred rats up to 2 years following dust exposure, this did not persist into old age. No mesotheliomas were induced by any treatments associated with iron ore dust, although the rats were shown to be susceptible to crocidolite asbestos-induced mesothelioma. In the mouse models, tumors which are normally seen only in aged animals were induced with a significant number of bronchial adenomas being recorded following intrapleural implantation of dust into inbred BALB/c mice. Leukemia/lymphoma associated with murine leukemia virus was increased following dust inhalation by inbred C57BL mice.}, } @article {pmid3032232, year = {1987}, author = {Huncharek, M}, title = {Chrysotile asbestos exposure and mesothelioma.}, journal = {British journal of industrial medicine}, volume = {44}, number = {4}, pages = {287-288}, pmid = {3032232}, issn = {0007-1072}, mesh = {Aged ; Asbestos/*adverse effects ; Asbestos, Serpentine ; Humans ; Mesothelioma/*chemically induced ; Middle Aged ; Pleural Neoplasms/*chemically induced ; }, } @article {pmid3820469, year = {1987}, author = {Garrahan, K}, title = {Mesothelioma: has patient had contact with even small amount of asbestos?.}, journal = {JAMA}, volume = {257}, number = {12}, pages = {1569-1570}, pmid = {3820469}, issn = {0098-7484}, mesh = {Asbestos/*adverse effects ; *Construction Materials ; Humans ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; }, } @article {pmid3828242, year = {1987}, author = {Hughes, JM and Weill, H and Hammad, YY}, title = {Mortality of workers employed in two asbestos cement manufacturing plants.}, journal = {British journal of industrial medicine}, volume = {44}, number = {3}, pages = {161-174}, pmid = {3828242}, issn = {0007-1072}, support = {HL-15092/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; Asbestos/*adverse effects ; *Construction Materials ; Humans ; Louisiana ; Lung Neoplasms/etiology/*mortality ; Male ; Mesothelioma/etiology/*mortality ; Occupational Diseases/etiology/*mortality ; Risk ; }, abstract = {In a study of the mortality experience of 6931 employees of two New Orleans asbestos cement products manufacturing plants over 95% were traced. Chrysotile was the primary fibre used in both plants. Plant 1 also used small amounts of amosite and, later, crocidolite irregularly whereas plant 2 used crocidolite steadily in pipe production. Previously reported exposure concentration estimates were revised, based on additional air sampling data and re-evaluation of these data. Workers in the two plants had similar duration of employment (overall, a mean of 3.8 years) and estimated exposure concentration (a mean of 7.6 million particles per cubic foot (mppcf)). Mortality was similar for these plants and comparable with Louisiana rates for all causes combined, nonmalignant causes, and primary cancers of specified sites other than lung. Short term workers from both plants showed raised and similar risk of lung cancer, but risk among longer term workers differed--for example, for workers employed over one year there was no excess in plant 1 (16 observed, 17.2 expected) but a significant excess in plant 2 (52 observed, 28.9 expected, p less than 0.001). After excluding short term workers, risk of lung cancer in plant 2 showed a significant trend with estimated cumulative asbestos exposure; using a conversion of 1.4 fibres/ml = 1 mppcf, the slope of the line was 0.0076. The slope for plant 1 was 0.0003. Among all workers (the 6931, plus 167 early employees) ten mesotheliomas had occurred up to 1984: two from plant 1, eight from plant 2. In plant 2 a case-control analysis found a relation between risk of mesothelioma and duration of employment (p less than 0.01) and proportion of time spent in the pipe area (p less than 0.01), thus adding to the evidence of a greater risk of mesothelioma from crocidolite than chrysotile asbestos. A review of the mortality findings of eight cohorts of asbestos cement workers is presented.}, } @article {pmid3583673, year = {1987}, author = {Howell, F and Clancy, L and Kelly, P and Callinan, I and Healy, T}, title = {Mesothelioma in the Republic of Ireland: a review in the context of new E.E.C. legislation.}, journal = {Irish medical journal}, volume = {80}, number = {3}, pages = {89-91}, pmid = {3583673}, issn = {0332-3102}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Humans ; Ireland ; Legislation, Medical ; Male ; Mesothelioma/*etiology ; Middle Aged ; Occupational Diseases/*etiology ; Pleural Neoplasms/*etiology ; }, } @article {pmid3549129, year = {1987}, author = {Bolen, JW}, title = {Tumors of serosal tissue origin.}, journal = {Clinics in laboratory medicine}, volume = {7}, number = {1}, pages = {31-50}, pmid = {3549129}, issn = {0272-2712}, mesh = {Asbestos/adverse effects ; Epithelium/pathology ; Humans ; Immunoenzyme Techniques ; Mesothelioma/diagnosis/etiology/*ultrastructure ; Microscopy, Electron ; Peritoneal Neoplasms/etiology/ultrastructure ; Pleural Neoplasms/etiology/ultrastructure ; Serous Membrane/pathology ; }, abstract = {Primary serosal neoplasms demonstrate a wide spectrum of growth patterns and biologic aggressiveness. The adenomatoid tumor is uniformly benign, whereas the diffuse malignant mesothelioma pursues a downhill clinical course, rapidly leading to fatality. The cystic peritoneal mesothelioma occupies an intermediate position characterized by persistent and/or recurrent disease but without progression to death. The distinction of an epithelial mesothelioma from metastatic adenocarcinoma remains a challenging problem. In the vast majority of cases, this can be accomplished by combining routine histochemistry, immunocytochemistry, and electron microscopy. The absence of epithelial mucins and nonreactivity with antibodies to CEA strongly favor mesothelioma. Ultrastructurally observed long, thin, sinuous surface microvilli without a glycocalix, well-developed desmosomes, and abundant tonofilaments add further support for a primary serosal neoplasm. The sarcomatoid mesothelioma can easily be confused with a chest-wall sarcoma. Despite lacking ultrastructural evidence of "epithelial" differentiation, immunocytochemical studies demonstrate cytokeratin. This distinguishes the sarcomatoid mesothelioma from most soft-tissue sarcomas. There remains a small number of cases, particularly those in the "poorly differentiated" or "transitional" category, in which the distinction between mesothelioma and metastatic carcinoma remains difficult. In this situation, it is imperative that all the clinical information be closely reviewed and a diligent search for a primary site be carried out. There are many parallels between reactive and neoplastic serosal tissue. The desmoplastic/sarcomatoid mesothelioma morphologically and immunocytochemically resembles the reactive multipotential subserosal cell (MSC) of injured serosal tissue, whereas the adenomatoid tumor, cystic peritoneal mesothelioma, and epithelial mesothelioma resemble surface mesothelium. The poorly differentiated mesothelioma resembles a stage of maturation between the two extremes, and thus the term "transitional" mesothelioma is suggested. The localized fibrous tumor of the pleura is unique among all other serosal neoplasms in its failure to express cytokeratin. It more closely resembles the unspecialized connective tissue fibroblast of normal serosal tissue, and thus may be more analogous to a soft-tissue tumor than to the remaining mesothelial-derived neoplasms.}, } @article {pmid3310070, year = {1987}, author = {Bateman, ED and Benatar, SR}, title = {Asbestos-induced diseases: clinical perspectives.}, journal = {The Quarterly journal of medicine}, volume = {62}, number = {239}, pages = {183-194}, pmid = {3310070}, issn = {0033-5622}, mesh = {Asbestos/*adverse effects ; Asbestosis/*etiology ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Pleural Diseases/etiology ; }, } @article {pmid2956635, year = {1987}, author = {Siskind, FB}, title = {The cost of compensating asbestos victims under the Occupational Disease Compensation Act of 1983.}, journal = {Risk analysis : an official publication of the Society for Risk Analysis}, volume = {7}, number = {1}, pages = {59-69}, doi = {10.1111/j.1539-6924.1987.tb00969.x}, pmid = {2956635}, issn = {0272-4332}, mesh = {Asbestosis/complications/*economics/mortality ; Costs and Cost Analysis ; Disability Evaluation ; Gastrointestinal Neoplasms/economics/etiology/mortality ; Humans ; Lung Neoplasms/economics/etiology/mortality ; Mesothelioma/economics/etiology/mortality ; United States ; Workers' Compensation/*economics/legislation & jurisprudence ; }, abstract = {The potentially huge financial liability due to asbestos product suits and the resulting filings for reorganization in bankruptcy by Manville, UNR Industries, Inc., and Amatex, has become a major public policy concern. In response to the problem several bills have been introduced in the Congress to provide compensation for asbestos (and other occupational disease) victims. This paper estimates the cost of compensating asbestos victims under the provisions of the "Occupational Disease Compensation Act of 1983," introduced by Congressman George Miller. Utilizing fatality projections from studies by Enterline, Selikoff, and Walker, and assumptions regarding likely claims filing and success rates, duration and degree of disability, and medical expenses, first year costs for this legislation are estimated to range from a low of $131 million to a high of $ billion. Present value cost estimates at a 2% real discount rate range from $3 billion to $56 billion. The paper also estimates the impact of possible modifications to the compensation provisions of the legislation. Reducing medical payments by the amount received from medicare would lower costs by 3-4%. Providing survivors with a 3-year lump sum benefit rather than a 5-year lump sum payment would save 20-25% as would offsetting the 5-year lump sum by expected social security old age and disability benefits. Combining all of these changes would reduce costs by almost 50%.}, } @article {pmid2950605, year = {1987}, author = {Becklake, MR}, title = {Control of asbestos-related disease in the RSA.}, journal = {South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde}, volume = {71}, number = {4}, pages = {208-210}, pmid = {2950605}, issn = {0256-9574}, mesh = {Asbestos/*adverse effects ; Asbestosis/*prevention & control ; Environmental Exposure ; Environmental Monitoring ; Humans ; Legislation as Topic ; Lung Neoplasms/*prevention & control ; Maximum Allowable Concentration ; Mesothelioma/*prevention & control ; South Africa ; Workers' Compensation ; }, } @article {pmid2880203, year = {1987}, author = {Talcott, J and Thurber, W and Gaensler, E and Antman, K and Li, FP}, title = {Mesothelioma in manufacturers of asbestos-containing cigarette filters.}, journal = {Lancet (London, England)}, volume = {1}, number = {8529}, pages = {392}, doi = {10.1016/s0140-6736(87)91773-9}, pmid = {2880203}, issn = {0140-6736}, mesh = {Air Pollutants, Occupational/*adverse effects ; Asbestos/*adverse effects ; Asbestos, Crocidolite ; Humans ; Male ; Mesothelioma/*etiology ; Middle Aged ; Occupational Diseases/*etiology ; Peritoneal Neoplasms/*etiology ; *Plants, Toxic ; *Nicotiana ; }, } @article {pmid3808809, year = {1987}, author = {}, title = {American Academy of Pediatrics Committee on Environmental Hazards: Asbestos exposure in schools.}, journal = {Pediatrics}, volume = {79}, number = {2}, pages = {301-305}, pmid = {3808809}, issn = {0031-4005}, mesh = {Asbestos/*adverse effects ; Asbestosis/etiology ; Child ; *Environmental Exposure ; Humans ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Risk ; *Schools ; United States ; United States Environmental Protection Agency ; }, } @article {pmid3802946, year = {1987}, author = {Kim, SB and Varkey, B and Choi, H}, title = {Diagnosis of malignant pleural mesothelioma by axillary lymph node biopsy.}, journal = {Chest}, volume = {91}, number = {2}, pages = {279-281}, doi = {10.1378/chest.91.2.279}, pmid = {3802946}, issn = {0012-3692}, mesh = {Axilla ; Biopsy ; Humans ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Male ; Mesothelioma/*pathology ; Middle Aged ; Pleural Neoplasms/*pathology ; }, abstract = {Diffuse malignant mesothelioma was diagnosed by axillary lymph node biopsy in a patient with brief asbestos exposure and extensive pleural masses. The clinical, radiographic and pathologic findings of this case are reported and lymph node involvement in DMM is briefly discussed.}, } @article {pmid3433233, year = {1987}, author = {Coutts, II and Gilson, JC and Kerr, IH and Parkes, WR and Turner-Warwick, M}, title = {Mortality in cases of asbestosis diagnosed by a pneumoconiosis medical panel.}, journal = {Thorax}, volume = {42}, number = {2}, pages = {111-116}, pmid = {3433233}, issn = {0040-6376}, mesh = {Adult ; Aged ; Asbestosis/complications/*mortality ; Follow-Up Studies ; Humans ; Lung Neoplasms/etiology/*mortality ; Male ; Mesothelioma/etiology/*mortality ; Middle Aged ; Respiration Disorders/etiology/*mortality ; Time Factors ; }, abstract = {One hundred and fifty five male cases of asbestosis certified by the London Pneumoconiosis Medical Panel during 1968-74 were followed up during 1978-9, 4-11 (mean 7.5) years after certification. Fifty nine patients had died, 23 (39%) from lung cancer, 6 (10%) from mesothelioma, and 11 (19%) from other respiratory causes. The number of observed deaths was 2.25 times greater than expected and 7.4 times greater than expected for lung cancer. Adenocarcinoma was the commonest histological type but other cell types were also increased. Finger clubbing (p less than 0.01) and percentage of predicted FEV1 (p less than 0.01) were of value in predicting death, but increasing profusion of small opacities greater than 1/0 (ILO/U-C international classification of radiographs of pneumoconiosis, 1971), duration of exposure to asbestos, time from first exposure to asbestos, and percentage of predicted vital capacity and transfer factor did not predict death.}, } @article {pmid3796694, year = {1987}, author = {}, title = {Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 4-1987. A 50-year-old man with recurrent pleuropulmonary abnormalities.}, journal = {The New England journal of medicine}, volume = {316}, number = {4}, pages = {198-208}, doi = {10.1056/NEJM198701223160407}, pmid = {3796694}, issn = {0028-4793}, mesh = {Asbestos/analysis ; Asbestosis/diagnosis ; Environmental Exposure ; Humans ; Lung/analysis ; Lung Neoplasms/pathology ; Male ; Mediastinal Neoplasms/pathology ; Mesothelioma/diagnosis/*pathology ; Middle Aged ; Neoplasm Invasiveness ; Pericardium/pathology ; Pleural Effusion/diagnosis/etiology ; Pleural Neoplasms/diagnosis/*pathology ; }, } @article {pmid3808555, year = {1987}, author = {Spain, W and Mayer, D}, title = {Policies have been confusing, but asbestos awareness improves. Interview by Sheri Hagen Poore.}, journal = {Occupational health & safety (Waco, Tex.)}, volume = {56}, number = {1}, pages = {44-51}, pmid = {3808555}, issn = {0362-4064}, mesh = {*Asbestos/adverse effects ; Asbestosis/etiology ; Decontamination ; England ; *Facility Regulation and Control ; Health Policy ; Humans ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Schools ; United States ; United States Environmental Protection Agency ; United States Occupational Safety and Health Administration ; }, } @article {pmid3687219, year = {1987}, author = {Gubéran, E and Usel, M}, title = {[Risk of cancer in locations containing asbestos: myth or reality?].}, journal = {Sozial- und Praventivmedizin}, volume = {32}, number = {4-5}, pages = {246-248}, pmid = {3687219}, issn = {0303-8408}, mesh = {Adult ; Asbestosis/*mortality ; Humans ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; Middle Aged ; Pleural Neoplasms/*mortality ; Risk Factors ; Switzerland ; }, abstract = {The risk of cancer induced by asbestos is proportional to the 'dose' inhaled (level X duration of exposure). Airborne asbestos fibre concentrations in buildings with sprayed asbestos insulation are very low. The estimation of life-long risk of cancer for people working continuously in this kind of buildings was made according to the Hughes and Weill's model. The lung cancer and mesothelioma mortality increase, attributable to asbestos, would be less than 0.1%, which means less than one death by century for all employees working in these buildings, in Switzerland. On the other hand, maintenance employees lying electric cables, pipes, etc., inside the asbestos-containing sprayed insulation, or workers transforming or pulling down these buildings, may be exposed to high asbestos fibre levels and should wear protective equipment.}, } @article {pmid3667856, year = {1987}, author = {Crump, KS and Allen, BC and Howe, RB and Crockett, PW}, title = {Time-related factors in quantitative risk assessment.}, journal = {Journal of chronic diseases}, volume = {40 Suppl 2}, number = {}, pages = {101S-111S}, doi = {10.1016/s0021-9681(87)80013-9}, pmid = {3667856}, issn = {0021-9681}, mesh = {Actuarial Analysis ; Age Factors ; Asbestos/adverse effects ; Benzene/adverse effects ; Humans ; Leukemia/mortality ; Mesothelioma/mortality ; Models, Biological ; Neoplasms/*mortality ; Occupational Diseases/mortality ; Risk ; Time Factors ; }, abstract = {In regulatory or decision-making contexts related to carcinogenic hazards, one would like to know the extra risks associated with various levels, durations, and ages of exposure to a carcinogen. To supply that information, quantitative risk assessments are required that make extrapolations on variables related to dose levels, timing of exposure, and age. Quantitative models that express age-specific mortality rates as functions of the exposure pattern and that allow such extrapolations to be made are presented. The uncertainty inherently associated with those extrapolations is discussed and is found to be exacerbated by small data sets and inadequate data availability. Specific examples are provided that involve asbestos-induced mesothelioma and leukemia caused by benzene exposure.}, } @article {pmid3659577, year = {1987}, author = {Constantopoulos, SH and Malamou-Mitsi, VD and Goudevenos, JA and Papathanasiou, MP and Pavlidis, NA and Papadimitriou, CS}, title = {High incidence of malignant pleural mesothelioma in neighbouring villages of Northwestern Greece.}, journal = {Respiration; international review of thoracic diseases}, volume = {51}, number = {4}, pages = {266-271}, doi = {10.1159/000195212}, pmid = {3659577}, issn = {0025-7931}, mesh = {Adult ; Asbestos/poisoning ; Female ; Greece ; Humans ; Male ; Mesothelioma/*epidemiology/etiology/mortality ; Middle Aged ; Pleura/pathology ; Pleural Neoplasms/*epidemiology/etiology/mortality ; Soil Pollutants/poisoning ; Space-Time Clustering ; }, abstract = {Between 1981 and 1985 seven patients from three villages of the Metsovo area in Northwestern Greece (population 5000) developed malignant pleural mesothelioma (MPM). The diagnosis was made with pleural biopsy and pleural fluid cytology. Six of these patients have died 18-24 months after the first symptoms (usually dyspnea on exertion) and 1 is still alive after 24 months. Seven MPMs in 5,000 in five years is about 280 times the expected incidence of 1/1,000,000/year. In the same area, endemic pleural calcifications linked to nonoccupational asbestos exposure have recently been reported, but none of our patients with MPM had pleural calcifications. The combination of MPM and pleural plaques in such a high frequency in the same area strongly suggests asbestos fiber as a common etiologic agent. On the other hand, the fact that the combination of MPM and pleural plaques did not occur in the same individuals, suggests a different response to this common offending agent.}, } @article {pmid3653990, year = {1987}, author = {Sandén, A and Järvholm, B}, title = {Cancer morbidity in Swedish shipyard workers 1978-1983.}, journal = {International archives of occupational and environmental health}, volume = {59}, number = {5}, pages = {455-462}, pmid = {3653990}, issn = {0340-0131}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Humans ; Male ; Middle Aged ; Neoplasms/diagnostic imaging/*epidemiology/mortality ; Occupational Diseases/diagnostic imaging/*epidemiology/mortality ; Pleura/diagnostic imaging ; Radiography ; *Ships ; Sweden ; }, abstract = {The cancer morbidity in 3787 shipyard workers was studied between 1978 and 1983. In these shipyards the use of asbestos was abandoned in 1972. The overall cancer morbidity was found to be similar to that of the male population of the same city, but there were four cases of mesothelioma. There were 11 cases of lung cancer, as opposed to 9.8 expected cases. Men with both heavy and long exposure to asbestos had no increased risk of lung cancer. The occurrence of pleural plaques was not associated with the risk of developing cancer.}, } @article {pmid3619589, year = {1987}, author = {Topov, J and Kolev, K}, title = {Unusual microscopic forms of experimental mesotheliomas.}, journal = {Archiv fur Geschwulstforschung}, volume = {57}, number = {3}, pages = {181-186}, pmid = {3619589}, issn = {0003-911X}, mesh = {Animals ; Asbestos ; Humans ; Mesothelioma/etiology/*pathology/ultrastructure ; Microscopy, Electron ; Peritoneal Neoplasms/etiology/*pathology/ultrastructure ; Pleural Neoplasms/etiology/*pathology/ultrastructure ; Rats ; }, abstract = {A lightmicroscopic study is made on 36 pleural and 68 peritoneal experimental mesotheliomas induced in white rats by intrapleural and intraperitoneal introduction of asbestos dust. The experimental tumors were compared with 10 spontaneous human mesotheliomas (8 pleural and 2 peritoneal mesotheliomas). The analysis revealed 4 types of morphologically specific experimental mesotheliomas, which could not be referred to the classifications used. In this group are included: a) large cell alveolar, b) small cell alveolar; c) adenocystic; d) with squamous metaplasia and keratinization. The observed unusual experimental lightmicroscopic forms of mesotheliomas support the opinion for great plastic abilities of mesothelium, and the presence of squamous metaplasia with keratinization may be a reason for considering it as a variant of epithelium.}, } @article {pmid3602591, year = {1987}, author = {Strankinga, WF and Sperber, M and Kaiser, MC and Stam, J}, title = {Accuracy of diagnostic procedures in the initial evaluation and follow-up of mesothelioma patients.}, journal = {Respiration; international review of thoracic diseases}, volume = {51}, number = {3}, pages = {179-187}, doi = {10.1159/000195200}, pmid = {3602591}, issn = {0025-7931}, mesh = {Asbestos/adverse effects ; Female ; Follow-Up Studies ; Humans ; Magnetic Resonance Spectroscopy ; Male ; Mesothelioma/*diagnosis/etiology/mortality ; Pleural Effusion/etiology ; Pleural Neoplasms/*diagnosis/etiology/mortality ; Tomography, X-Ray Computed ; }, abstract = {The present study contains the review of 30 patients with malignant mesothelioma of the pleura, examined and treated at our institution. In an attempt to compare various methods of diagnosis in this entity, emphasis was laid on specific abilities and limitation of investigations such as pleural biopsy, pleural fluid cytology, diagnostic thoracoscopy and thoracotomy and radiological studies including computed tomography and magnetic resonance imaging. Clinical management problems encountered in this neoplasm are also discussed.}, } @article {pmid3599573, year = {1987}, author = {Kishimoto, T and Okada, K and Sato, T and Ono, T and Masuda, Y and Ito, H}, title = {[A case of malignant mesothelioma caused by exposure to asbestos].}, journal = {Nihon Kyobu Shikkan Gakkai zasshi}, volume = {25}, number = {1}, pages = {125-129}, pmid = {3599573}, issn = {0301-1542}, mesh = {Aged ; Asbestos/*adverse effects ; Humans ; Lung Neoplasms/*etiology/pathology ; Male ; Mesothelioma/*etiology/pathology ; Occupational Diseases/*etiology/pathology ; Radiography, Thoracic ; Time Factors ; }, } @article {pmid3578286, year = {1987}, author = {Paci, E and Buiatti, E and Geddes, M}, title = {A case-referent study of lung tumors in non-asbestos textile workers.}, journal = {American journal of industrial medicine}, volume = {11}, number = {3}, pages = {267-273}, doi = {10.1002/ajim.4700110304}, pmid = {3578286}, issn = {0271-3586}, mesh = {Aged ; Asbestos/adverse effects ; Epidemiologic Methods ; Humans ; Italy ; Lung Neoplasms/epidemiology/*etiology ; Male ; Middle Aged ; Occupational Diseases/epidemiology/*etiology ; Risk ; *Textile Industry ; Time Factors ; }, abstract = {A case series in the Province of Florence showed an increased risk of mesothelioma in textile workers (nonasbestos) and a survey of working conditions confirmed potential exposure to asbestos. In order to investigate the risk in textile workers, including some specific job titles, a case-referent study on lung tumors was carried out. The lung cancer cases included 441 males with histologically confirmed primary lung cancer during the period 1980-1983. Referents included 1,075 males selected from two hospitals and matched for age, sex, and smoking habits. Those who had "ever worked" in the textile industry showed an adjusted odds ratio of 1.52 (95% C.I. 1-2.25) compared with other "industrial workers." This moderately increased risk is maintained in selected jobs in the textile industry. An analysis of the modifying effect of time factors showed an increased risk in the period of 15-35 years from the date of first employment in the industry. The results support the hypothesis that a probable risk of lung cancer in textile workers in the Prato area was related to asbestos exposure.}, } @article {pmid3578285, year = {1987}, author = {Quinn, MM and Kriebel, D and Buiatti, E and Paci, E and Sini, S and Vannucchi, G and Zappa, M}, title = {An asbestos hazard in the reprocessed textile industry.}, journal = {American journal of industrial medicine}, volume = {11}, number = {3}, pages = {255-266}, doi = {10.1002/ajim.4700110303}, pmid = {3578285}, issn = {0271-3586}, support = {2507RR05446-24/RR/NCRR NIH HHS/United States ; N01-C0-65341//PHS HHS/United States ; }, mesh = {Asbestos/*adverse effects ; Humans ; Italy ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Occupational Diseases/*etiology ; *Textile Industry ; }, abstract = {Epidemiologic studies have identified an excess risk of lung cancer and mesothelioma among workers in the reprocessed textile industry in Prato, Italy. These studies suggested that there may have been asbestos hazard in this industry although exposure was not known to exist. An industrial hygiene investigation was conducted to determine whether there was previous or current asbestos exposure in the industry. Walk-through surveys, environmental sampling, process documentation, and management and worker interviews were conducted in 13 textile reprocessing establishments. Polypropylene bags that once contained asbestos were found in 2 of the 13. Asbestos bags were cut open and used to cover bales of rags which were then distributed throughout the world. Workers were exposed to asbestos while handling the bags which were contaminated with chrysotile, amosite, and crocidolite. Additional sources of asbestos exposure that may have existed in the past in the industry are also discussed.}, } @article {pmid3578284, year = {1987}, author = {Paci, E and Dini, S and Buiatti, E and Seniori Costantini, A and Lenzi, S and Zappa, M}, title = {Malignant mesothelioma in non-asbestos textile workers in Florence.}, journal = {American journal of industrial medicine}, volume = {11}, number = {3}, pages = {249-254}, doi = {10.1002/ajim.4700110302}, pmid = {3578284}, issn = {0271-3586}, mesh = {Aged ; Asbestos/adverse effects ; Female ; Humans ; Italy ; Male ; Mesothelioma/*etiology ; Middle Aged ; Occupational Diseases/*etiology ; *Textile Industry ; }, abstract = {By means of a review of histological diagnosis in the Pathology Department of the University of Florence, suspected cases of malignant mesothelioma, diagnosed in the period 1979-1984, were identified. Study of histological specimens permitted the selection of 13 cases of malignant mesothelioma resident in the Province of Florence. To these cases, referents were matched for age, sex, and year of hospital admission, with residence weighted for the general population of the Province. Both cases and referents (or their next of kin) completed an occupational questionnaire detailing possible occupational exposures. Out of the 13 cases of mesothelioma, 6 were textile workers and 5 of these were "rag-sorters". There were only 5 textile workers among the 52 controls. No asbestos cloth production plants have been in operation in the area from which the cases and referents are derived. Possible sources of exposure to asbestos in the textile industry of this area are discussed.}, } @article {pmid3427974, year = {1987}, author = {Turk, J and Kenda, M and Janezic, A and Kranjec, I and Rakovec, P and Cijan, A and Gasparac, A and Jezernik, J and Gracnar, R}, title = {Pericardial mesothelioma.}, journal = {Cor et vasa}, volume = {29}, number = {5}, pages = {392-394}, pmid = {3427974}, issn = {0010-8650}, mesh = {Adult ; Heart Neoplasms/*diagnosis ; Humans ; Male ; Mesothelioma/*diagnosis/surgery ; *Pericardium/pathology ; }, abstract = {The case of a 44-year old man, never exposed to asbestos, who died from a pericardial mesothelioma is described. The diagnosis was made by surgical examination. Two weak transient episodes of amelioration, the first accomplished with pronison administration and the other one by radiotherapy, were registered.}, } @article {pmid3305596, year = {1987}, author = {Chang, SN and White, LE and Scott, WD}, title = {Assessing asbestos exposure potential in nonindustrial settings.}, journal = {Journal of community health}, volume = {12}, number = {2-3}, pages = {176-184}, pmid = {3305596}, issn = {0094-5145}, mesh = {Air Pollution/*analysis/prevention & control ; Asbestos/*analysis ; Environmental Exposure ; Microscopy, Electron ; Microscopy, Phase-Contrast ; }, abstract = {The presence of asbestos containing materials (ACM) in office and commercial buildings is a significant environmental problem. Asbestosis, mesothelioma and lung cancer have been linked with industrial exposure to airborne asbestos. The extensive use of asbestos products in buildings has raised concerns about the widespread exposure of the general public to asbestos in nonoccupational settings. The presence of asbestos in a building does not necessarily mean that significant exposure of the occupants of the building has occurred, but it is important that the asbestos be monitored regularly to ensure that fibers do not become airborne. If ACM are contained within a matrix and not disturbed, exposure is unlikely. However, if the asbestos becomes friable (crumbling) or if building maintenance, repair, renovation or other activities disturb ACM, airborne asbestos fibers may be a source of exposure to the occupants of the building. Currently, asbestos exposure assessment is conducted by a phase contrast light microscope (PCM) technique. Due to its inherent limitation in resolution and the generic counting rules used, analysis by the PCM method underestimates the airborne asbestos fiber concentration as compared to analysis by transmission electron microscopy (TEM). It is important that the air monitoring results analyzed by PCM be interpreted carefully in conjunction with a survey by a professional to judge the physical condition of the ACM in buildings. Exposure levels to airborne asbestos fibers vary from day to day and depend on the physical condition of the material involved and the type of operating and maintenance program in place.(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid3124509, year = {1987}, author = {Karlinger, K and Gere, J and Németh, L and Galgóczy, G}, title = {Abdominal mesothelioma induced by occupational asbestos exposure.}, journal = {Acta morphologica Hungarica}, volume = {35}, number = {1-2}, pages = {71-76}, pmid = {3124509}, issn = {0236-5391}, mesh = {Asbestos/*adverse effects ; Asbestosis/pathology ; Humans ; Male ; Mesothelioma/*etiology/pathology ; Middle Aged ; Occupational Diseases/*etiology/pathology ; Peritoneal Neoplasms/*etiology/pathology ; Pulmonary Fibrosis/diagnostic imaging/etiology ; Radiography ; }, abstract = {Asbestos bodies were demonstrated within an abdominal mesothelioma, proving the tumour-inductive role of asbestos fibres. Asbestos fibres were also found earlier in a case of bile duct carcinoma (17).}, } @article {pmid3099726, year = {1987}, author = {Yousem, SA and Hochholzer, L}, title = {Malignant mesotheliomas with osseous and cartilaginous differentiation.}, journal = {Archives of pathology & laboratory medicine}, volume = {111}, number = {1}, pages = {62-66}, pmid = {3099726}, issn = {0003-9985}, mesh = {Aged ; Cartilage/*pathology ; Female ; Humans ; Male ; Mesothelioma/diagnostic imaging/*pathology ; Middle Aged ; *Ossification, Heterotopic ; Pleural Neoplasms/diagnostic imaging/*pathology ; Radiography ; }, abstract = {This report describes ten examples of diffuse pleural tumors felt to represent malignant mesotheliomas with osseous and cartilaginous differentiation. Typically, the patients involved were elderly whites who presented with chest pain, bloody pleural effusions, and diffuse and nodular pleural disease on chest roentgenograms. An asbestos-exposure history was indicated in six of the ten patients. Seven cases were malignant fibrous mesotheliomas, and three were biphasic mesotheliomas. Results of immunoperoxidase studies for cytoplasmic keratin were positive in three of six cases of malignant fibrous mesothelioma.}, } @article {pmid3028136, year = {1987}, author = {Amandus, HE and Wheeler, R}, title = {The morbidity and mortality of vermiculite miners and millers exposed to tremolite-actinolite: Part II. Mortality.}, journal = {American journal of industrial medicine}, volume = {11}, number = {1}, pages = {15-26}, doi = {10.1002/ajim.4700110103}, pmid = {3028136}, issn = {0271-3586}, mesh = {*Aluminum Silicates ; *Asbestos, Amphibole ; Humans ; Lung Neoplasms/etiology ; Male ; Mesothelioma/etiology ; Minerals/*adverse effects ; *Mining ; Montana ; Occupational Diseases/etiology/*mortality ; Silicon Dioxide/*adverse effects ; Smoking ; Time Factors ; }, abstract = {The vermiculite ore and concentrate of a mine and mill located near Libby, Montana was found to be contaminated with a fiber of the tremolite/acetinolite series. A study was conducted to estimate the exposure-response relationship for mortality for 575 men who had been hired prior to 1970 and employed at least 1 year at the Montana site. Individual cumulative fiber exposure (fiber-years) was calculated. Results indicated that mortality from nonmalignant respiratory disease (NMRD) and lung cancer was significantly increased compared to the U.S. white male population. For those workers more than 20 years since hire, the standard mortality rate (SMR) for lung cancer (ICDA 162-163) was 84.7, 225.1, 109.3, and 671.3 for less than 50, 50-99, 100-399, and more than 399 fiber-years respectively. Corresponding results for NMRD (ICDA 460-519) were 327.8, 283.5, 0, and 278.4. Based on a linear model for greater than 20 years since hire, the estimated percentage increase in lung cancer mortality risk was 0.6% for each fiber-year of exposure. At 5 fiber-years, the estimated percentage was 2.9% from an unrestricted (nonthreshold) linear model and 0.6% from a survival model.}, } @article {pmid2884870, year = {1987}, author = {Churg, A and Wiggs, B}, title = {Accumulation of long asbestos fibers in the peripheral upper lobe in cases of malignant mesothelioma.}, journal = {American journal of industrial medicine}, volume = {11}, number = {5}, pages = {563-569}, doi = {10.1002/ajim.4700110508}, pmid = {2884870}, issn = {0271-3586}, mesh = {Asbestos/metabolism/*poisoning ; Asbestos, Amosite ; Humans ; Lung/metabolism/pathology ; Lung Neoplasms/*etiology/metabolism/ultrastructure ; Male ; Mesothelioma/*etiology/metabolism/ultrastructure ; Occupational Diseases/*etiology/metabolism/pathology ; Particle Size ; }, abstract = {Animal studies suggest that mesothelioma is most effectively induced by fibers longer than 8 mu. However, studies of asbestos fibers recovered from human lungs in cases of mesothelioma indicate that, at least in large-scale samples, relatively few fibers meet this size criterion, perhaps implying that the animal data do not apply to man. Since asbestos concentration in lung is known to be extremely inhomogeneous, it is also possible that long fibers may selectively accumulate in specific sites, such as under the pleura. To examine this possibility, we selected ten cases of mesothelioma that contained relatively large amounts of amosite asbestos and extracted fibers from an 0.5-cm-thick strip of subpleural tissue and an area 3-cm deep to the subpleural sample for upper and lower lobes. Amosite fibers were identified and sized by electron microscopic techniques. Fibers in the peripheral upper lobe were significantly longer, broader, and of higher aspect ratio than those in the central upper lobe. The lower lobe showed a reverse pattern, with longer fibers and broader fibers in the central sample. These data indicate that the two lobes behave differently in regard to fiber size, with selective accumulation of long fibers in the peripheral upper lobe, but not in the peripheral lower lobe. Whether these differences reflect differences in initial deposition of fibers within the lung, or, more likely, specific redistribution of fibers, is unclear, but in either case, accumulation of long fibers immediately under the upper lobe pleura may be important in the genesis of mesothelioma.}, } @article {pmid2835925, year = {1987}, author = {Smith, DM and Ortiz, LW and Archuleta, RF and Johnson, NF}, title = {Long-term health effects in hamsters and rats exposed chronically to man-made vitreous fibres.}, journal = {The Annals of occupational hygiene}, volume = {31}, number = {4B}, pages = {731-754}, doi = {10.1093/annhyg/31.4b.731}, pmid = {2835925}, issn = {0003-4878}, mesh = {Abdominal Neoplasms/etiology ; Animals ; Asbestos/toxicity ; Asbestos, Crocidolite ; Ceramics/toxicity ; Cricetinae ; Female ; Glass/administration & dosage/*toxicity ; Lung Neoplasms/etiology ; Male ; Mesocricetus ; Mesothelioma/etiology ; Minerals/toxicity ; Rats ; Rats, Inbred Strains ; Time Factors ; }, } @article {pmid2825103, year = {1987}, author = {Roggli, VL and Kolbeck, J and Sanfilippo, F and Shelburne, JD}, title = {Pathology of human mesothelioma. Etiologic and diagnostic considerations.}, journal = {Pathology annual}, volume = {22 Pt 2}, number = {}, pages = {91-131}, pmid = {2825103}, issn = {0079-0184}, mesh = {Aluminum Silicates/adverse effects ; Animals ; Asbestos/adverse effects ; Diagnosis, Differential ; Histocytochemistry ; Humans ; Immunoenzyme Techniques ; Mesothelioma/etiology/*pathology ; Microscopy, Electron ; Neoplasms, Radiation-Induced ; Peritoneal Neoplasms/etiology/*pathology ; Pleural Neoplasms/etiology/*pathology ; Zeolites ; }, } @article {pmid2441238, year = {1987}, author = {Bianchi, C and Brollo, A and Bittesini, L and Ramani, L}, title = {[Hyaline plaques of the pleura and domestic exposure to asbestos].}, journal = {La Medicina del lavoro}, volume = {78}, number = {1}, pages = {44-49}, pmid = {2441238}, issn = {0025-7818}, mesh = {Aged ; Asbestosis/etiology/genetics/*pathology ; Autopsy ; Clothing ; Environmental Exposure ; Female ; Household Work ; Humans ; *Hyalin ; Male ; Mesothelioma/etiology ; Middle Aged ; Pleura/*pathology ; Pleural Neoplasms/etiology ; Risk ; }, } @article {pmid3830113, year = {1986}, author = {Omenn, GS and Merchant, J and Boatman, E and Dement, JM and Kuschner, M and Nicholson, W and Peto, J and Rosenstock, L}, title = {Contribution of environmental fibers to respiratory cancer.}, journal = {Environmental health perspectives}, volume = {70}, number = {}, pages = {51-56}, pmid = {3830113}, issn = {0091-6765}, mesh = {*Air Pollutants ; Asbestos ; Construction Materials ; Humans ; Lung Neoplasms/*etiology ; Microclimate ; Respiratory Tract Neoplasms/*etiology ; Risk ; }, abstract = {This article reviews studies of the carcinogenicity of mineral fibers, notably asbestos, and presents seven major recommendations for further research. Mineral fibers represent the greatest cause--after cigarette smoke--of respiratory cancer due to air pollutants. Past asbestos exposure may currently account for 2000 mesothelioma deaths per year and 4000 to 6000 lung cancer deaths per year. All major commercial types of asbestos (crocidolite, amosite, and chrysotile) can cause each of the major asbestos-related respiratory diseases. Lung cancers in asbestos-exposed individuals probably do not have a different distribution of histological types from that of non-asbestos-related lung cancers. Nonoccupational exposures are likely to be associated with malignant disease outcomes qualitatively similar to those associated with occupational exposures. Further investigations of fibers are needed to characterize the relationships among physicochemical properties, patterns of migration and clearance, dose, and adverse health effects. Transmission electron microscopy has been found to be the preferred method of analysis of environmental fibers. Relations among time factors (e.g., age at first exposure), dose, and risk for adverse health effects require analyses of existing and new epidemiologic studies of exposed cohorts. Concomitant exposure, behavioral factors, and host factors affecting susceptibility to asbestos should be identified.}, } @article {pmid3810935, year = {1986}, author = {Olsen, JH and Andersson, M}, title = {[Asbestos-induced cancer in Denmark].}, journal = {Ugeskrift for laeger}, volume = {148}, number = {49}, pages = {3328-3333}, pmid = {3810935}, issn = {0041-5782}, mesh = {Asbestos/*adverse effects ; Denmark ; Female ; Humans ; Male ; Mesothelioma/*chemically induced/epidemiology ; Pleural Neoplasms/*chemically induced/epidemiology ; Risk ; }, } @article {pmid3026434, year = {1986}, author = {Ozesmi, M and Karlsson-Parra, A and Hillerdal, G and Forsum, U}, title = {Phenotypic characterisation of peripheral blood lymphoid cells in people exposed to fibrous zeolite.}, journal = {British journal of industrial medicine}, volume = {43}, number = {12}, pages = {830-833}, pmid = {3026434}, issn = {0007-1072}, mesh = {Adult ; Aluminum Silicates/*adverse effects ; Environmental Exposure ; Female ; Humans ; Leukocyte Count ; Lymphocytes/*pathology ; Male ; Mesothelioma/*etiology/pathology ; Middle Aged ; Phenotype ; T-Lymphocytes, Helper-Inducer/pathology ; T-Lymphocytes, Regulatory/pathology ; Zeolites ; }, abstract = {Among inhabitants of the village of Karain in Turkey there is an extremely high incidence of malignant mesothelioma, most probably due to exposure to erionite, which is a fibrous zeolite and similar in appearance and properties to asbestos. This mineral may be found in the dust in the village. To characterise possible disturbances in the immune system of people exposed to fibrous zeolite, a phenotypic characterisation of lymphoid cells in the peripheral blood of 74 immigrants to Sweden from Karain was performed. Compared with normal controls, the mean percentages of Leu 4+ cells (Pan-T) and Leu 3a+ cells ("helper/inducer" T cells) were significantly decreased, whereas the mean percentage of Leu 2a+ cells ("suppressor/cytotoxic" T cells) was normal, leading to a significant reduction of the Leu 3a/Leu 2a subset ratio. The percentage of B cells (Leu 12+ cells) was significantly increased, whereas the percentages of both HLA-DR+ and HLA-DQ+ cells were normal. The percentage of natural killer cells (NK) and killer (K) cells as defined by the monoclonal anti-Leu 7 and anti-Leu 11b were also normal. These findings indicate that exposure to fibrous zeolite causes a numerical imbalance between the two phenotypically different T cell subsets similar to that seen in asbestos exposed individuals.}, } @article {pmid2431665, year = {1986}, author = {DaValle, MJ and Faber, LP and Kittle, CF and Jensik, RJ}, title = {Extrapleural pneumonectomy for diffuse, malignant mesothelioma.}, journal = {The Annals of thoracic surgery}, volume = {42}, number = {6}, pages = {612-618}, doi = {10.1016/s0003-4975(10)64593-6}, pmid = {2431665}, issn = {0003-4975}, mesh = {Actuarial Analysis ; Adult ; Aged ; Diaphragm/surgery ; Female ; Humans ; Male ; Mesothelioma/*mortality/*surgery ; Middle Aged ; Palliative Care/methods ; Pericardium/surgery ; Pleura/*surgery ; Pleural Neoplasms/mortality/*surgery ; Pneumonectomy/*methods/mortality ; Polyethylene Terephthalates ; Postoperative Care/methods ; Prostheses and Implants ; }, abstract = {Extrapleural pneumonectomy for malignant mesothelioma is a radical procedure that entails en bloc removal of the parietal pleura, lung, pericardium, and diaphragm. Minimal tumor remains after this procedure; palliation and occasional long-term survival may be achieved in properly selected patients. Extrapleural pneumonectomy for diffuse, malignant mesothelioma was done in 33 patients (27 male and 6 female) with 18 procedures on the left side and 15 on the right. There was a history of exposure to asbestos in 16 (48%) of the patients. Histological classification revealed that 20 tumors were epithelial, 10 were mixed, and 3 were sarcomatous. Good palliation, defined as survival for 24 months with a return to fairly normal activities, was obtained in 8 patients (24%) and survival for 36 months was achieved in 5 patients. Three patients died of the disease at 59 months, 60 months, and 82 months. There were 3 operative deaths (9.1%), and serious postoperative complications occurred in 8 patients (24%). Postoperative adjunctive therapy consisting of chemotherapy or irradiation or both was given to approximately one-half of the patients. These findings indicate that extrapleural pneumonectomy for malignant mesothelioma can be done with an acceptable morbidity and mortality. Palliation is achieved in 24% of patients, and there may be an occasional long-term survivor.}, } @article {pmid3775370, year = {1986}, author = {Aroesty, J and Wolf, K}, title = {Risk from exposure to asbestos.}, journal = {Science (New York, N.Y.)}, volume = {234}, number = {4779}, pages = {923}, doi = {10.1126/science.3775370}, pmid = {3775370}, issn = {0036-8075}, mesh = {Asbestos/*adverse effects ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Risk ; }, } @article {pmid3024695, year = {1986}, author = {Gardner, MJ and Winter, PD and Pannett, B and Powell, CA}, title = {Follow up study of workers manufacturing chrysotile asbestos cement products.}, journal = {British journal of industrial medicine}, volume = {43}, number = {11}, pages = {726-732}, pmid = {3024695}, issn = {0007-1072}, mesh = {Asbestos/*adverse effects ; Asbestos, Serpentine ; Construction Materials/*adverse effects ; England ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/mortality ; Male ; Neoplasms/mortality ; Occupational Diseases/etiology/*mortality ; }, abstract = {A cohort study has been carried out of 2167 subjects employed between 1941 and 1983 at an asbestos cement factory in England. The production process incorporated the use of chrysotile asbestos fibre only, except for a small amount of amosite during four months in 1976. Measured airborne fibre concentrations available since 1970 from personal samplers showed mean levels below 1 fibre/ml, although higher levels had probably occurred previously in certain areas of the factory. No excess of lung cancer was observed in the mortality follow up by comparison with either national or local death rates, and analyses of subgroups of the workforce by job, exposure level, duration of employment, duration since entry, or calendar years of employment gave no real suggestion of an asbestos related excess for this cause of death. There was one death from pleural mesothelioma and one with asbestosis mentioned as an associated cause on the death certificate, but neither is thought to be linked to asbestos exposure at this factory. Other suggested asbestos related cancers, such as laryngeal and gastrointestinal, did not show raised risks. Although the durations of exposure were short in this study, the findings are consistent with two other studies of workers exposed to low concentrations of chrysotile fibre in the manufacture of asbestos cement products which reported no excess mortality.}, } @article {pmid3752702, year = {1986}, author = {Schenker, MB and Garshick, E and Muñoz, A and Woskie, SR and Speizer, FE}, title = {A population-based case-control study of mesothelioma deaths among U.S. railroad workers.}, journal = {The American review of respiratory disease}, volume = {134}, number = {3}, pages = {461-465}, doi = {10.1164/arrd.1986.134.3.461}, pmid = {3752702}, issn = {0003-0805}, support = {ES-05157/ES/NIEHS NIH HHS/United States ; HL-07427/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Humans ; Male ; Mesothelioma/etiology/*mortality ; Middle Aged ; Occupational Diseases/etiology/*mortality ; Time Factors ; United States ; }, abstract = {We have completed a case-control analysis of mesothelioma deaths among current and retired U.S. railroad employees. Cause-specific death certificates were obtained for 87% of 15,059 deaths reported by the railroad retirement board, and 20 mesotheliomas were identified according to death certificate diagnosis. A 10:1 matched analysis with railroad workers dying of nonmalignant, nonaccidental causes yielded a very strong association with prior railroad work in jobs with potential asbestos exposure (odds ratio = 7.2, 95% lower confidence limit = 3.3). Consideration of railroad occupations with regular asbestos exposures (e.g., skilled trades, steam locomotive repair) yielded an odds ratio of 21.4 (95% lower confidence limit = 8.7), but the occupations with potential intermittent exposure (e.g., engineers, firemen, carmen) yielded a nonsignificant odds ratio of 2.3 (95% lower confidence limit = 0.5). Applying mesothelioma mortality rates from this study to the population of U.S. railroad workers at risk yields an estimate of 416 cases of mesothelioma occurring among U.S. railroad workers between 1981 and 2000.}, } @article {pmid3021597, year = {1986}, author = {Kogan, FM and Berzin, SA}, title = {[Incidence of pleural mesothelioma after exposure to chrysotile and asbestos dust].}, journal = {Gigiena truda i professional'nye zabolevaniia}, volume = {}, number = {9}, pages = {9-12}, pmid = {3021597}, issn = {0016-9919}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Asbestos, Serpentine ; Dust/adverse effects ; Humans ; Mesothelioma/*etiology ; Middle Aged ; Pleural Neoplasms/*etiology ; }, } @article {pmid3020957, year = {1986}, author = {Corn, M}, title = {Asbestos and disease: an industrial hygienist's perspective.}, journal = {American Industrial Hygiene Association journal}, volume = {47}, number = {9}, pages = {515-523}, doi = {10.1080/15298668691390151}, pmid = {3020957}, issn = {0002-8894}, mesh = {Air Pollutants, Occupational/adverse effects ; Asbestos/*adverse effects ; Asbestos, Serpentine ; Asbestosis/*etiology ; Dust/adverse effects ; Humans ; Lung Neoplasms/etiology ; Maximum Allowable Concentration ; Mesothelioma/etiology ; Pleural Neoplasms/etiology ; Risk ; }, abstract = {I have traced a personal thirty year journey of involvement with asbestos in the workplace and the nonoccupational environment, one still in progress, in an attempt to extract selected lessons for the industrial hygienist. Lessons for other professions, namely medicine, law and management have been studiously avoided in the interests of the scope of this presentation and permissible time. There are certainly numerous other lessons to contemplate. The movement of asbestos from the occupational to the nonoccupational environment is a case study that will undoubtedly be followed in the future by other potentially toxic materials. We must determine our position as a profession with regard to the tools we utilize, the procedures we follow, and our understanding of our moral and legal obligations to prepare for the often scientifically and technically unsupportable positions assumed by others, including governmental agencies, in their zeal to bring about change. We must discourage the opportunistic distortion of professional practices in these matters, and must issue well considered statements as a profession, statements relevant to the way these matters are addressed by society. We have a responsibility to lend perspective to these issues, to not permit understandably emotional responses to documented past severe health effects in other areas, such as the case of asbestos in the workplace, to carry over into conditions of very low exposures in the public domain. We must remind people of the relevance of dose-response and toxicological principles to assessment of risk.(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid2948455, year = {1986}, author = {Contreras Rodríguez, R and Rebollar Pliego, L and Trevethan Cravioto, S and Medina Mora, O}, title = {[Primary mesothelioma of the pericardium. Report of 2 cases and review of the literature].}, journal = {Archivos del Instituto de Cardiologia de Mexico}, volume = {56}, number = {5}, pages = {403-411}, pmid = {2948455}, issn = {0020-3785}, mesh = {Adult ; Female ; Heart Neoplasms/*diagnosis/pathology ; Humans ; Mesothelioma/*diagnosis/pathology ; Middle Aged ; Myocardium/pathology ; *Pericardium ; }, abstract = {We described two adult females with primary pericardial mesothelioma. There was not history of asbestos exposure. The clinical picture suggested pericardial constriction, with predominantly right sided heart failure. Anatomically; one case was of a nodular type, being the other diffuse. On histology both cases were of the fibrous type. The second case was less differentiated; it perforated the right atrial wall creating an intracavitary mass. A review of the literature is made.}, } @article {pmid3783520, year = {1986}, author = {Karunaharan, T}, title = {Malignant mesothelioma of the tunica vaginalis in an asbestos worker.}, journal = {Journal of the Royal College of Surgeons of Edinburgh}, volume = {31}, number = {4}, pages = {253-254}, pmid = {3783520}, issn = {0035-8835}, mesh = {Adult ; Asbestos/*adverse effects ; Humans ; Male ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; Testicular Neoplasms/*etiology ; }, } @article {pmid3758755, year = {1986}, author = {Pylev, LN and Kulagina, TF and Vasil'eva, LA and Piatina, GP and Uzunov, P}, title = {[Evaluation of the carcinogenicity of the respirable dust of Bulgarian anthophyllite asbestos].}, journal = {Gigiena truda i professional'nye zabolevaniia}, volume = {}, number = {8}, pages = {54-56}, pmid = {3758755}, issn = {0016-9919}, mesh = {Animals ; Asbestos/*toxicity ; *Asbestos, Amphibole ; Bulgaria ; Dust/*adverse effects ; Female ; Male ; Mesothelioma/*chemically induced ; Pleural Neoplasms/*chemically induced ; Rats ; }, } @article {pmid3091826, year = {1986}, author = {Lemesch, C and Katz, L and Steinitz, R}, title = {Mesothelioma in Israel (1973-1982).}, journal = {Journal of the Royal Society of Health}, volume = {106}, number = {4}, pages = {141-142}, doi = {10.1177/146642408610600407}, pmid = {3091826}, issn = {0264-0325}, mesh = {Adolescent ; Adult ; Aged ; Asbestos/*adverse effects ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Infant, Newborn ; Israel ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Occupational Diseases/*epidemiology ; }, } @article {pmid3017091, year = {1986}, author = {Austin, MB and Fechner, RE and Roggli, VL}, title = {Pleural malignant mesothelioma following Wilms' tumor.}, journal = {American journal of clinical pathology}, volume = {86}, number = {2}, pages = {227-230}, doi = {10.1093/ajcp/86.2.227}, pmid = {3017091}, issn = {0002-9173}, mesh = {Adult ; Female ; Humans ; Kidney Neoplasms/*complications/pathology ; Mesothelioma/*etiology/pathology ; Neoplasms, Multiple Primary/*pathology ; Pleural Neoplasms/*etiology/pathology ; Wilms Tumor/*complications/pathology ; }, abstract = {A 28-year-old woman had a left pleural malignant mesothelioma develop, which resulted in her death. At age four, she had undergone a left nephrectomy for Wilms' tumor and had received radiation therapy to the left renal fossa and to the right lung, the latter for a presumed diagnosis of metastatic tumor. Asbestos body counts of digested lung tissue were within the normal range. This is the fourth reported case of malignant mesothelioma following Wilms' tumor and is the first to provide quantitative analysis of asbestos in the lung.}, } @article {pmid3790419, year = {1986}, author = {Ribak, J and Herman, A and Selikoff, IJ}, title = {Electrolyte changes in mesothelioma.}, journal = {British journal of diseases of the chest}, volume = {80}, number = {3}, pages = {280-282}, doi = {10.1016/0007-0971(86)90064-1}, pmid = {3790419}, issn = {0007-0971}, mesh = {Asbestosis/blood ; Chlorides/blood ; Electrolytes/*blood ; Humans ; Male ; Mesothelioma/*blood ; Occupational Diseases/*blood ; Peritoneal Neoplasms/*blood ; Pleural Neoplasms/*blood ; Potassium/blood ; Sodium/blood ; }, abstract = {Little has been reported concerning electrolyte changes among patients with mesothelioma. Two studies have suggested that hyponatraemia is particularly common among them and should lead to suspicion of inappropriate secretion of antidiuretic hormone in those patients (Perks et al. 1979; Siafakas et al. 1984). We reviewed serum electrolyte changes in three groups of patients: 48 cases of pleural mesothelioma, 89 of peritoneal mesothelioma, associated with asbestos exposure, and 149 of asbestosis. Five of 48 (10.4%) patients with pleural mesothelioma, 17 of 89 (19.1%) with peritoneal mesothelioma, and 23 of 149 (15.4%) patients with asbestosis without mesothelioma, had hyponatraemia. No statistically significant difference among the groups was found. These findings do not support the proposal that hyponatraemia is unusually common when mesothelioma is present, at least not among patients whose neoplasms are related to asbestos exposure.}, } @article {pmid3784180, year = {1986}, author = {Shishido, S and Iwai, K and Sanada, H and Tsukagoshi, K and Yamada, H and Mori, J and Kawabata, Y and Sato, M}, title = {[A case of malignant pleural mesothelioma showing a lower lung field mass shadow in a construction worker using asbestos].}, journal = {Nihon Kyobu Shikkan Gakkai zasshi}, volume = {24}, number = {7}, pages = {810-816}, pmid = {3784180}, issn = {0301-1542}, mesh = {Asbestos/*adverse effects ; Humans ; Male ; Mesothelioma/*diagnostic imaging/etiology ; Middle Aged ; Occupational Diseases/*diagnostic imaging/etiology ; Pleural Neoplasms/*diagnostic imaging/etiology ; Radiography ; }, } @article {pmid3731743, year = {1986}, author = {Chandler, KW}, title = {Asbestos-related pleuropulmonary disorders.}, journal = {Comprehensive therapy}, volume = {12}, number = {7}, pages = {45-54}, pmid = {3731743}, issn = {0098-8243}, mesh = {Asbestos/*adverse effects ; Asbestosis/*pathology ; Carcinoma, Bronchogenic/etiology ; Humans ; Lung Diseases/diagnostic imaging/*etiology ; Lung Neoplasms/etiology ; Mesothelioma/etiology/pathology ; Pleura/diagnostic imaging/pathology ; Pleural Diseases/diagnostic imaging/*etiology/pathology ; Pleural Effusion/etiology ; Pleural Neoplasms/etiology ; Pulmonary Atelectasis/etiology/pathology ; Tomography, X-Ray Computed ; }, } @article {pmid3532578, year = {1986}, author = {Huncharek, M}, title = {The biomedical and epidemiological characteristics of asbestos-related diseases: a review.}, journal = {The Yale journal of biology and medicine}, volume = {59}, number = {4}, pages = {435-451}, pmid = {3532578}, issn = {0044-0086}, mesh = {Animals ; Asbestos/*adverse effects/history ; Asbestosis/etiology ; Epidemiologic Methods ; Gastrointestinal Neoplasms/etiology ; History, 20th Century ; History, Ancient ; Humans ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Neoplasms, Experimental/etiology ; }, abstract = {The purpose of this paper is to provide the reader with an overview of the biomedical and epidemiological characteristics of asbestos-related disease based upon currently available information. Epidemiological and experimental data developed over the past 20 years have greatly added to our knowledge of the biological effects of asbestos, particularly in relation to clinical disease. This information has substantially strengthened the evidence linking asbestos to specific health effects. Lung cancer and mesothelioma are clearly the most important asbestos-related causes of death among exposed individuals, although the accumulated data is suggestive of the existence of an excess risk of gastrointestinal and a variety of other neoplasms. Animal studies confirm the human epidemiological results and indicate that all commercially available fiber types are capable of producing lung cancer and mesothelioma. Experimental implantation and injection studies also show that the carcinogenicity of mineral fibers (including asbestos) is directly related to their dimensionality and not their chemical composition. Although the asbestos-related medical and scientific literature is voluminous, many issues related to the biological activity of asbestos fibers are as yet unresolved. Due to experimental and analytical limitations, questions concerning risk at low-level exposure, dose-response relationships, and individual susceptibility remain problematic.}, } @article {pmid3453179, year = {1986}, author = {Krousel, T and Garcas, N and Rothschild, H}, title = {Familial clustering of mesothelioma: a report on three affected persons in one family.}, journal = {American journal of preventive medicine}, volume = {2}, number = {4}, pages = {186-188}, pmid = {3453179}, issn = {0749-3797}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Female ; Humans ; Lung Neoplasms/etiology/*genetics ; Mesothelioma/etiology/*genetics ; Middle Aged ; Pedigree ; }, abstract = {Pleural mesothelioma developed in at least three members of a family of first-degree relatives. Only one member had probable direct asbestos exposure. An analysis of these cases and their circumstances leads us to suspect that a latent genetic susceptibility may be present in this cancer-prone family.}, } @article {pmid3090605, year = {1986}, author = {Lilienfeld, DE and Gunderson, PD}, title = {The "missing cases" of pleural malignant mesothelioma in Minnesota, 1979-81: preliminary report.}, journal = {Public health reports (Washington, D.C. : 1974)}, volume = {101}, number = {4}, pages = {395-399}, pmid = {3090605}, issn = {0033-3549}, mesh = {Aged ; Asbestos/adverse effects ; *Death Certificates ; Diagnostic Errors ; Epidemiologic Methods ; Female ; Humans ; Male ; Mesothelioma/epidemiology/etiology/*mortality ; Middle Aged ; Minnesota ; }, abstract = {Malignant mesothelioma is a sentinel neoplasm for population exposure to asbestiform fibers. Public health officials may be alerted to temporal or spatial clustering of malignant mesothelioma through analyses of vital records, such as death certificates. Hence, the maintenance of the integrity of the vital statistics system, particularly the cause of death statement on the death certificate, is very important. The report by a northeastern Minnesota radiologist in January 1985 of an elevated prevalence of pleural plaques (related to asbestiform fiber exposure) to the Minnesota Department of Health resulted in an investigation of pleural malignant mesothelioma mortality trends in that area and in three other similar areas in the State. In that study, we noted that in several instances malignant mesothelioma (either intrathoracic or unspecified site) was listed on the death certificate in such a manner as to imply that the neoplasm was either a lung cancer or a malignancy of an unspecified site. The effect of this misclassification is to underestimate the mortality from malignant mesothelioma by fourfold to eightfold. Given the importance of malignant mesothelioma as a proxy for past asbestos exposure, it is necessary to determine the extent of such misclassification for all deaths in the United States.}, } @article {pmid3015180, year = {1986}, author = {Kelsey, KT and Yano, E and Liber, HL and Little, JB}, title = {The in vitro genetic effects of fibrous erionite and crocidolite asbestos.}, journal = {British journal of cancer}, volume = {54}, number = {1}, pages = {107-114}, pmid = {3015180}, issn = {0007-0920}, support = {CA-09078/CA/NCI NIH HHS/United States ; ES-00002/ES/NIEHS NIH HHS/United States ; ES-07069/ES/NIEHS NIH HHS/United States ; }, mesh = {Aluminum Silicates/*toxicity ; Animals ; Asbestos/*toxicity ; Asbestos, Crocidolite ; Chromosome Aberrations ; Cricetinae ; Cricetulus ; Dose-Response Relationship, Drug ; Fibroblasts/drug effects ; Mutation/drug effects ; Polyploidy ; Sister Chromatid Exchange/*drug effects ; Zeolites ; }, abstract = {Epidemiologic evidence has recently identified an association between an endemic outbreak of pleural and peritoneal mesothelioma in the Urgup region of Turkey and exposure to zeolite fibres. This malignancy is usually associated with exposure to asbestos dusts whose mineralogical characteristics differ from those of zeolites. The present study further defines the in vitro biologic activity of erionite, a common zeolite fibre found in the Urgup region of Turkey. Both erionite and crocidolite asbestos fibres were clastogenic in synchronous Chinese hamster ovary (CHO) fibroblasts. Both fibres also altered CHO ploidy. Erionite, unlike crocidolite or Min-U-Sil quartz, caused a slight increase in sister chromatid exchanges in synchronous CHO cells. Neither erionite nor crocidolite was mutagenic in a human lymphoblastoid cell line. Erionite fibres thus produced in vitro cytogenic changes similar to those caused by asbestiform mineral dusts and, like asbestos fibres, did not induce mutations in human lymphoblastoid cells.}, } @article {pmid3013278, year = {1986}, author = {McDonald, JC and McDonald, AD and Armstrong, B and Sebastien, P}, title = {Cohort study of mortality of vermiculite miners exposed to tremolite.}, journal = {British journal of industrial medicine}, volume = {43}, number = {7}, pages = {436-444}, pmid = {3013278}, issn = {0007-1072}, mesh = {*Aluminum Silicates ; *Asbestos, Amphibole ; Follow-Up Studies ; Humans ; Male ; *Mining ; Montana ; Occupational Diseases/*chemically induced/mortality ; Respiratory Tract Diseases/chemically induced ; Respiratory Tract Neoplasms/chemically induced ; Silicic Acid/*adverse effects ; Silicon Dioxide/*adverse effects ; }, abstract = {A cohort of 406 men employed before 1963 for at least one year in a vermiculite mine in Montana was followed up until July 1983. The vermiculite ore as fed to the mill contained 4-6% of amphibole fibre in the tremolite series. Vital status was established in all but one of the 406 and death certificates were obtained and coded for 163 of the 165 men who died. Compared with white men in the United States, the cohort experienced excess mortality from all causes (SMR 1.17), respiratory cancer (SMR 2.45), non-malignant respiratory disease (SMR 2.55), and accidents (SMR 2.14). Four deaths were from malignant mesothelioma (proportional mortality 2.4%). Compared with Montana death rates, the SMR for respiratory cancer was somewhat higher (3.03). Man-year analyses of respiratory cancer and estimated cumulative exposure gave a relation that did not depart significantly from linearity. The results of this and case-referent analyses indicate an increased risk of mortality from respiratory cancer in this cohort of about 1% for each fibre year of exposure. In relation to estimated exposure the mortality experienced by the cohort from both lung cancer and mesothelial tumours was higher than in chrysotile mining.}, } @article {pmid3718883, year = {1986}, author = {Wagner, JC and Moncrieff, CB and Coles, R and Griffiths, DM and Munday, DE}, title = {Correlation between fibre content of the lungs and disease in naval dockyard workers.}, journal = {British journal of industrial medicine}, volume = {43}, number = {6}, pages = {391-395}, pmid = {3718883}, issn = {0007-1072}, mesh = {Aged ; Asbestos/*adverse effects/analysis ; England ; Humans ; Lung/analysis/ultrastructure ; Lung Diseases/*etiology/mortality/pathology ; Male ; Middle Aged ; *Military Personnel ; Naval Medicine ; Occupational Diseases/*etiology ; }, abstract = {In the period 1966-82 lungs from 333 workers who had been employed at a Royal Naval dockyard were referred to the MRC Pneumoconiosis Unit where they were investigated for the severity of asbestosis, the presence of tumours, and an assessment of mineral fibre content and the type and amount of mineral present. The occupational exposure to mineral dust has been coded for 189 of these cases. There is good correlation between the severity of asbestosis and the coded exposures, electron microscopic mineral fibre count, and the fibre count as seen under the light microscope. The information collected showed that mesotheliomas occurred in those who had had minimal or slight asbestosis, by contrast with the pulmonary carcinomas found in those with moderate to severe asbestosis. The amphibole (crocidolite and amosite) lung content correlated with severity of asbestosis.}, } @article {pmid3531828, year = {1986}, author = {McCaughey, WT}, title = {Neoplastic asbestos-induced disease.}, journal = {The Mount Sinai journal of medicine, New York}, volume = {53}, number = {6}, pages = {416-420}, pmid = {3531828}, issn = {0027-2507}, mesh = {Asbestos/*adverse effects ; Humans ; Lung Neoplasms/etiology/pathology ; Mesothelioma/etiology/pathology ; Neoplasms/*etiology ; }, } @article {pmid3297003, year = {1986}, author = {Davies, CN}, title = {Diseases associated with the inhalation of asbestos dust.}, journal = {Arhiv za higijenu rada i toksikologiju}, volume = {37}, number = {2}, pages = {253-274}, pmid = {3297003}, issn = {0004-1254}, mesh = {Air Pollutants, Occupational/analysis ; Asbestos/*adverse effects/analysis ; *Asbestosis ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; Pleural Neoplasms/*etiology ; }, } @article {pmid2872911, year = {1986}, author = {Davis, JM and Addison, J and Bolton, RE and Donaldson, K and Jones, AD and Smith, T}, title = {The pathogenicity of long versus short fibre samples of amosite asbestos administered to rats by inhalation and intraperitoneal injection.}, journal = {British journal of experimental pathology}, volume = {67}, number = {3}, pages = {415-430}, pmid = {2872911}, issn = {0007-1021}, mesh = {Animals ; Asbestos/*toxicity ; Asbestos, Amosite ; Bronchi/ultrastructure ; Granulation Tissue/ultrastructure ; Lung/ultrastructure ; Lung Neoplasms/etiology ; Macrophages/ultrastructure ; Male ; Microscopy, Electron ; Pulmonary Fibrosis/*etiology/pathology ; Rats ; Rats, Inbred Strains ; }, abstract = {For many years it has been accepted that fibre dimensions are the most important factor in the development of asbestos related disease with long fibres being more dangerous than short for all types of asbestos. This information has been derived from in vitro experiments and injection or implantation experiments since the kilogramme quantities of specially prepared dusts that are necessary for long term inhalation have not been available. The present study has taken advantage of the availability of a sample of amosite produced so that almost all fibres were less than 5 micron in length. The effects of this dust were compared to dust prepared from raw amosite that contained a very high proportion of long fibres. Previous data from studies with UICC amosite, which was intermediate in length, were also available for comparison. At the end of 12 months of dust inhalation, significantly more short fibre amosite was present in the lung tissue compared to the long but while the long fibre dust caused the development of widespread pulmonary fibrosis, no fibrosis at all was found in animals treated with short fibre. One third of animals treated with long fibre dust developed pulmonary tumours or mesotheliomas but no pulmonary neoplasms were found in animals treated with short fibre dust. Following intraperitoneal injection, the long fibre amosite produced mesotheliomas in 95% of animals with a mean induction period of approximately 500 days. With short fibre dust, only a single mesothelioma developed after 837 days. In previous inhalation studies with UICC amosite, relatively little pulmonary fibrosis had developed and only two benign pulmonary tumours. This would suggest that to produce a significant carcinogenic response in rat lung tissue amosite fibres must be longer than those in the UICC preparation. Following the injection of UICC amosite, however, mesotheliomas developed in the same proportion of animals and with the same mean induction period as with long fibre dust. From this it would appear that while very short fibres exhibit little carcinogenicity to either lung or mesothelial tissues, mesotheliomas can be produced by dust preparations consisting of shorter fibres than are needed to produce tumours.}, } @article {pmid3006905, year = {1986}, author = {Wagner, JC}, title = {Mesothelioma and mineral fibers.}, journal = {Cancer}, volume = {57}, number = {10}, pages = {1905-1911}, doi = {10.1002/1097-0142(19860515)57:10<1905::aid-cncr2820571003>3.0.co;2-j}, pmid = {3006905}, issn = {0008-543X}, mesh = {Aluminum Silicates/adverse effects ; Asbestos/*adverse effects ; *Asbestos, Amphibole ; Asbestos, Serpentine ; Environmental Exposure ; Female ; Humans ; Male ; Mesothelioma/*etiology ; Middle Aged ; Minerals/*adverse effects ; Occupational Diseases/etiology ; Peritoneal Neoplasms/etiology ; Pleural Neoplasms/*etiology ; Time Factors ; Zeolites ; }, } @article {pmid2871356, year = {1986}, author = {Berry, CL and Jones, TJ}, title = {Early-onset, asbestos-associated mesothelioma?.}, journal = {Lancet (London, England)}, volume = {1}, number = {8489}, pages = {1094}, doi = {10.1016/s0140-6736(86)91355-3}, pmid = {2871356}, issn = {0140-6736}, mesh = {Asbestos/*adverse effects ; Humans ; Lung Neoplasms/*etiology/pathology ; Male ; Mesothelioma/*etiology/pathology ; Time Factors ; }, } @article {pmid3706090, year = {1986}, author = {DeLuca, SA and Rhea, JT}, title = {Pleural mesothelioma.}, journal = {American family physician}, volume = {33}, number = {5}, pages = {103-104}, pmid = {3706090}, issn = {0002-838X}, mesh = {Asbestos/*adverse effects ; Humans ; Mesothelioma/*diagnostic imaging/etiology ; Pleural Neoplasms/*diagnostic imaging/etiology ; Radiography ; }, } @article {pmid2424930, year = {1986}, author = {Lew, F and Tsang, P and Holland, JF and Warner, N and Selikoff, IJ and Bekesi, JG}, title = {High frequency of immune dysfunctions in asbestos workers and in patients with malignant mesothelioma.}, journal = {Journal of clinical immunology}, volume = {6}, number = {3}, pages = {225-233}, pmid = {2424930}, issn = {0271-9142}, support = {5-P30-CA 23102/CA/NCI NIH HHS/United States ; CA-15936-04/CA/NCI NIH HHS/United States ; }, mesh = {*Asbestos/adverse effects ; Cell Line ; Cytotoxicity, Immunologic ; Flow Cytometry ; Humans ; *Immunity, Cellular ; Interferons/immunology ; Killer Cells, Natural/immunology ; Leukemia, Myeloid ; Mesothelioma/*immunology ; Phenotype ; Recombinant Proteins/immunology ; T-Lymphocytes/classification/*immunology ; T-Lymphocytes, Helper-Inducer/immunology ; }, abstract = {We have examined the primary immune responses, the numbers of total T (T11+) cells, T-helper (T4+) cells, T-suppressor (T8+) cells, and natural killer (NK) (Leu7+) cells, in 118 healthy control subjects and compared the data to those obtained from 20 patients with clinically diagnosed malignant mesothelioma and 375 long-term asbestos workers without neoplasia. The absolute numbers of total T (T11+) and T-helper (T4+) cells were normal in asbestos workers without neoplasia but were significantly reduced in patients with mesothelioma. T-suppressor (T8+) cells, on the other hand, remained unchanged in the patients but were significantly elevated among the asbestos workers. This resulted in a marked reduction in T-helper (Th) to T-suppressor (Ts) ratios in mesothelioma patients and in asbestos workers. Seventy percent of the mesothelioma patients (14 of 20) had significantly depressed NK-cell activity which could be augmented but not normalized by coincubation in patients' peripheral blood lymphocytes (PBL) with interferon (IFN). Among the asbestos workers three distinctive subgroups could be identified: heightened (H-NK), normal (N-NK), and low (L-NK) NK activity. The NK activity of the L-NK group could be stimulated but not normalized by coincubation with IFN, a finding closely resembling that in malignant mesothelioma patients. Phenotyping of the circulating NK cells revealed a unique Leu7+ subset in increased numbers with a brightly fluorescent property in stable mesothelioma patients with relatively stable or slowly progressive disease and in more than 30% of the asbestos workers.(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid3082913, year = {1986}, author = {Victor, LD and Talamonti, WJ}, title = {Asbestos lung disease.}, journal = {Hospital practice (Office ed.)}, volume = {21}, number = {4}, pages = {257-268}, pmid = {3082913}, issn = {8750-2836}, mesh = {Asbestosis/*diagnosis/etiology/pathology ; Environmental Exposure ; Humans ; Lung/diagnostic imaging/pathology ; Lung Neoplasms/chemically induced/diagnosis/pathology ; Mesothelioma/chemically induced/diagnosis/pathology ; Pulmonary Fibrosis/chemically induced/diagnosis/pathology ; Radiography ; }, } @article {pmid3956307, year = {1986}, author = {}, title = {Asbestos related disease.}, journal = {Chest}, volume = {89}, number = {4 Suppl}, pages = {366S-368S}, doi = {10.1378/chest.89.4.366s}, pmid = {3956307}, issn = {0012-3692}, mesh = {Asbestos/*adverse effects ; Asbestosis/*diagnostic imaging ; Humans ; Mesothelioma/*etiology ; Pleural Diseases/diagnostic imaging/*etiology ; Pleural Neoplasms/diagnostic imaging/*etiology ; Radiography ; }, } @article {pmid3716518, year = {1986}, author = {Luther, R and Preisler, J and Bärsch, J}, title = {[Asbestos carcinogenesis from clinical and hypothetical viewpoints].}, journal = {Zeitschrift fur die gesamte innere Medizin und ihre Grenzgebiete}, volume = {41}, number = {7}, pages = {211-214}, pmid = {3716518}, issn = {0044-2542}, mesh = {Adult ; Asbestos/*adverse effects ; Biopsy ; Female ; Humans ; Lung Neoplasms/pathology ; Lymph Nodes/pathology ; Mesothelioma/*pathology ; Neoplasm Recurrence, Local/pathology ; Occupational Diseases/pathology ; Pleura/pathology ; Pleural Neoplasms/*pathology ; Risk ; }, abstract = {On the basis of a case of mesothelioma of the pleura in a 28-year-old female who among our patients had the longest survival time after establishment of the diagnosis (31 months) the authors adopt a definite attitude to the problems of asbestosis. It can be regarded as ascertained that after asbest exposition a systemic contamination of the organism occurs. Apart from the inhalative intake further possibilities of the asbest fibre incorporation and the elimination are referred to. As to the cancerogenesis of asbest-induced malignomas the existing theories appear at present still insufficient; analogies to Virchow's irritation theory are possible in the serosa tumours.}, } @article {pmid2870260, year = {1986}, author = {Elmes, P and Browne, K}, title = {Mesothelioma shortly after brief exposure to asbestos.}, journal = {Lancet (London, England)}, volume = {1}, number = {8483}, pages = {746}, doi = {10.1016/s0140-6736(86)91145-1}, pmid = {2870260}, issn = {0140-6736}, mesh = {Asbestos/*adverse effects ; Humans ; Lung Neoplasms/*etiology ; Male ; Mesothelioma/*etiology ; Time Factors ; }, } @article {pmid3956392, year = {1986}, author = {Woitowitz, HJ and Lange, HJ and Rödelsperger, K and Ulm, K and Giesen, T and Woitowitz, RH and Pache, L}, title = {[Occupational cancer study of asbestos: possibilities and limits of epidemiologic studies on the causes of death in West Germany].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {111}, number = {13}, pages = {490-499}, doi = {10.1055/s-2008-1068478}, pmid = {3956392}, issn = {0012-0472}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Female ; Germany, West ; Humans ; Lung Neoplasms/chemically induced/mortality ; Male ; Mesothelioma/chemically induced/mortality ; Middle Aged ; Neoplasms/*chemically induced/mortality ; Occupational Diseases/*chemically induced/mortality ; Risk ; Sex Factors ; Smoking ; Time Factors ; }, abstract = {The study is based on 3990 men and women exposed to asbestos dust for at least three years at their place of work, and prospectively and epidemiologically examined since 1 January, 1977. By 31 December, 1983, 336 had been registered as having died. Calculation of standard mortality rates indicates that the incidence of malignant tumour as cause of death was much higher than in the general population of the FRG, that of fatal mesothelioma about 100 times as high. Standard mortality rate for lung cancer was increased by 48% and 175%, respectively, depending on whether exposure to asbestos dust had ended after (subgroup I) or before (subgroup II) 1 January, 1972. Proportional mortality rate of 43% of tumours at all locations, with about 14% lung cancer and about 9% fatal mesothelioma cases in subgroup II, approaches the internationally recognized frequency of asbestos-associated tumours.}, } @article {pmid3947577, year = {1986}, author = {Hodgson, JT and Jones, RD}, title = {Mortality of asbestos workers in England and Wales 1971-81.}, journal = {British journal of industrial medicine}, volume = {43}, number = {3}, pages = {158-164}, pmid = {3947577}, issn = {0007-1072}, mesh = {Adolescent ; Adult ; Asbestos/*adverse effects ; Asbestosis/mortality ; England ; Gastrointestinal Neoplasms/mortality ; Humans ; Lung Neoplasms/mortality ; Male ; Mesothelioma/mortality ; Middle Aged ; Occupational Diseases/*mortality ; Smoking ; Time Factors ; Wales ; }, abstract = {A national study of British asbestos workers is briefly described and the mortality experience of 31 150 male asbestos workers in England and Wales who had been medically examined at least once as part of that survey is presented. The survey population is divided into workers with occupational exposure to asbestos before the inception of the 1969 Asbestos Regulations and those who worked with asbestos only after 1969. Of the 1128 who had died, 897 had worked before 1969; 34 of the death certificates received for these men mentioned mesothelioma and for another nine asbestosis was reported in the absence of mesothelioma or lung cancer. A statistically significant excess of lung cancer (SMR 136) was found. For the post-1969 workers, one case of asbestosis and one case of mesothelioma were reported, but further investigation of these cases showed probable occupational exposure to asbestos many years before 1969. The time from first exposure for this section of the population is too short to exclude an excess of asbestos related disease. The most noticeable excess of asbestos related disease was seen among the insulation workers who had more than twice (SMR 256) the expected number of deaths from lung cancer, and for whom almost 10% of all death certificates mentioned mesothelioma. No excess of any alimentary tract cancer was found and the population showed a significant deficit of large bowel cancer mortality (SMR 54).}, } @article {pmid3746069, year = {1986}, author = {Ebihara, I}, title = {[A case of malignant peritoneal mesothelioma following asbestos exposure].}, journal = {Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine}, volume = {75}, number = {3}, pages = {400-405}, doi = {10.2169/naika.75.400}, pmid = {3746069}, issn = {0021-5384}, mesh = {Asbestos/*adverse effects ; Humans ; Lung/pathology ; Male ; Mesothelioma/*etiology ; Middle Aged ; Occupational Diseases/*etiology ; Peritoneal Neoplasms/*etiology ; Peritoneum/pathology ; }, } @article {pmid3715773, year = {1986}, author = {Wagner, JC and Pooley, FD}, title = {Mineral fibres and mesothelioma.}, journal = {Thorax}, volume = {41}, number = {3}, pages = {161-166}, pmid = {3715773}, issn = {0040-6376}, mesh = {Asbestos/*adverse effects ; Environmental Exposure ; Humans ; Mesothelioma/*etiology ; Minerals/*adverse effects ; Peritoneal Neoplasms/etiology ; Pleural Neoplasms/etiology ; }, } @article {pmid3699199, year = {1986}, author = {Kestner, JF}, title = {Asbestos associated disease of the lung and pleura.}, journal = {Delaware medical journal}, volume = {58}, number = {3}, pages = {161-173}, pmid = {3699199}, issn = {0011-7781}, mesh = {Adenocarcinoma/*diagnosis ; Asbestosis/*diagnosis ; Humans ; Lung Neoplasms/*diagnosis ; Male ; Mesothelioma/*diagnosis ; Middle Aged ; Pleural Neoplasms/*diagnosis ; }, } @article {pmid2942032, year = {1986}, author = {Simonsen, J}, title = {Pseudomesotheliomatous carcinoma of the lung with asbestos exposure.}, journal = {The American journal of forensic medicine and pathology}, volume = {7}, number = {1}, pages = {49-51}, doi = {10.1097/00000433-198603000-00010}, pmid = {2942032}, issn = {0195-7910}, mesh = {Aged ; Asbestos/*adverse effects ; Carcinoma/*pathology ; Diagnosis, Differential ; Humans ; Lung Neoplasms/chemically induced/*pathology ; Male ; Mesothelioma/chemically induced/*pathology ; Occupational Diseases/chemically induced ; Workers' Compensation ; }, abstract = {A case of peripheral lung carcinoma clinically and anatomically simulating a malignant mesothelioma in a man who had been exposed to silicium as well as asbestos during more than 20 years of employment in industry is presented. Results of the microscopic examination of routine, stained sections were inconclusive and the importance of demonstrating mucin in the neoplastic cells by use of special staining is emphasized.}, } @article {pmid2868350, year = {1986}, author = {Booth, SJ and Weaver, EJ}, title = {Malignant pleural mesothelioma five years after domestic exposure to blue asbestos.}, journal = {Lancet (London, England)}, volume = {1}, number = {8478}, pages = {435}, doi = {10.1016/s0140-6736(86)92385-8}, pmid = {2868350}, issn = {0140-6736}, mesh = {Adult ; Asbestos/*adverse effects ; Construction Materials/*adverse effects ; Humans ; Male ; Mesothelioma/*etiology ; Pleural Neoplasms/*etiology ; Time Factors ; }, } @article {pmid3962388, year = {1986}, author = {Kolev, K and Usunov, P and Wlasov, W}, title = {[Experimental asbestos-induced mesotheliomas--character and peculiarities].}, journal = {Zeitschrift fur die gesamte Hygiene und ihre Grenzgebiete}, volume = {32}, number = {2}, pages = {89-90}, pmid = {3962388}, issn = {0049-8610}, mesh = {Animals ; Asbestosis/*pathology ; Mesothelioma/*pathology ; Peritoneal Neoplasms/*pathology ; Peritoneum/pathology ; Pleura/pathology ; Pleural Neoplasms/*pathology ; Rats ; }, } @article {pmid3957626, year = {1986}, author = {Bianchi, C and Bittesini, L and Brollo, A}, title = {Asbestos exposure and Alzheimer disease.}, journal = {Italian journal of neurological sciences}, volume = {7}, number = {1}, pages = {145-151}, pmid = {3957626}, issn = {0392-0461}, mesh = {Aged ; Alzheimer Disease/*chemically induced/complications/pathology/psychology ; Asbestos/*adverse effects ; Asbestosis/complications/pathology ; Cerebral Cortex/pathology ; Environmental Exposure ; Hippocampus/pathology ; Humans ; Lung/pathology ; Male ; Memory Disorders/complications ; Mesothelioma/complications/pathology ; Pleural Neoplasms/complications/pathology ; }, abstract = {10 cases in which an asbestos-related disease (malignant pleural mesothelioma or asbestosis) was associated with severe Alzheimer type lesions in the brain are reported. The patients, all males aged between 67 and 78 years, had been occupationally exposed to asbestos in the shipbuilding industry. The hypothesis that asbestos is a favoring factor in the genesis of Alzheimer disease is discussed.}, } @article {pmid3004552, year = {1986}, author = {Davis, JM and Addison, J and Bolton, RE and Donaldson, K and Jones, AD}, title = {Inhalation and injection studies in rats using dust samples from chrysotile asbestos prepared by a wet dispersion process.}, journal = {British journal of experimental pathology}, volume = {67}, number = {1}, pages = {113-129}, pmid = {3004552}, issn = {0007-1021}, mesh = {Animals ; Asbestos/*toxicity ; Asbestos, Serpentine ; Dust ; Lung/ultrastructure ; Lung Neoplasms/etiology/pathology/ultrastructure ; Mesothelioma/etiology ; Pulmonary Fibrosis/etiology/pathology ; Rats ; Rats, Inbred Strains ; Respiration ; }, abstract = {Long term inhalation studies and intraperitoneal injection studies in rats were undertaken with a series of chrysotile asbestos dusts. Three dust samples were generated from chrysotile modified by the wet dispersion process (WDC) and one was from unmodified chrysotile. Following a 1 year inhalation period, all the chrysotile samples proved extremely fibrogenic and carcinogenic and there were no significant differences between the WDC dusts and normal chrysotile. In all experimental groups approximately 25% of animals developed pulmonary carcinomas and in the oldest rats advanced interstitial fibrosis occupied on average 10% of all lung tissue. In the injection studies all the dust samples produced mesotheliomas in over 90% of animals. Very little chrysotile remained in the lungs of the animals that survived longest following dust inhalation and what there was was present as individual chrysotile fibrils. It is suggested that chrysotile is potentially the most harmful variety of asbestos as shown in these and other animal studies but that it is removed from lung tissue quite rapidly. In the long lived human species this may mean that except where exposure levels are very high and of long duration, chrysotile should be less hazardous than other asbestos types.}, } @article {pmid3002780, year = {1986}, author = {Bolton, RE and Addison, J and Davis, JM and Donaldson, K and Jones, AD and Miller, BG and Wright, A}, title = {Effects of the inhalation of dusts from calcium silicate insulation materials in laboratory rats.}, journal = {Environmental research}, volume = {39}, number = {1}, pages = {26-43}, doi = {10.1016/s0013-9351(86)80005-6}, pmid = {3002780}, issn = {0013-9351}, mesh = {Animals ; Body Weight ; *Calcium Compounds ; Construction Materials/*adverse effects ; Dust/*adverse effects/analysis ; Injections, Intraperitoneal ; Lung/metabolism/pathology ; Lymph Nodes/pathology ; Macrophages/pathology ; Male ; Neoplasms, Experimental/etiology/pathology ; Pulmonary Fibrosis/etiology/pathology ; Rats ; *Silicates ; Silicic Acid/metabolism/*toxicity ; Silicon Dioxide/*toxicity ; }, abstract = {The effects of respirable dust from three commercially produced calcium silicate insulation materials were examined in laboratory rats by long-term inhalation and injection techniques. These calcium silicate products have been used as replacements for asbestos in the insulation of the engine rooms of ships, and the particle size distribution of the dust clouds generated for the experimental study closely matched those found in ships during the installation of this type of material. One year of exposure to a dust cloud of 10 mg/m3 of respirable dust had no discernible effect on the length of survival of treated animals compared to controls. No pulmonary lesions were found that appeared associated with the inhalation of calcium silicate per se, but one sample did contain significant amounts of quartz and this did produce a few small pulmonary nodules. While two small pulmonary neoplasms, one malignant and one benign, were found in dusted animals, neither was the cause of death, and the incidence was not significantly different from the control group where no tumors were found. One peritoneal mesothelioma was found in an animal from one of the inhalation groups, but this was considered to be a spontaneous tumor as none of over 100 animals injected intraperitoneally with 25 mg of calcium silicate developed these tumors. While the white blood cell count of dusted animals, compared to controls, was significantly raised in all treated groups at the end of the dusting period, these figures were within the published normal ranges for laboratory rats. It was concluded that the three tested calcium silicate products were harmless to the rats of this species at the doses tested.}, } @article {pmid3002778, year = {1986}, author = {Dumas, L and Pagé, M}, title = {Growth changes of 3T3 cells in the presence of mineral fibers.}, journal = {Environmental research}, volume = {39}, number = {1}, pages = {199-204}, doi = {10.1016/s0013-9351(86)80022-6}, pmid = {3002778}, issn = {0013-9351}, mesh = {Animals ; Asbestos/*toxicity ; Asbestos, Serpentine ; *Cell Division ; Cell Line ; Fibroblasts/cytology ; Mice ; }, abstract = {The relationship between exposure to asbestos fibers and the development of mesothelioma or bronchial carcinoma prompted many countries to ban its use from commercial products. The biological mechanism by which asbestos induces or promotes mesothelioma or carcinoma is still unknown. In order to study the influence of fibers on the cell surface, 3T3 fibroblasts were cultured in the presence of various mineral fibers. The acute cytotoxicity produced by mineral fibers was evaluated by the trypan blue dye exclusion method; growth of 3T3 cells was measured as well as the maximum cell density at saturation. We found that growth of 3T3 cells was slower in the presence of chrysotile while light microscopy revealed an increased cellular chromogenicity and a modification of the cell-cell arrangement in the presence of this fiber. We describe an assay in which chrysotile causes an increase in the maximum cell density at saturation.}, } @article {pmid3524008, year = {1986}, author = {Michalczak, W}, title = {[Cumulative effects of smoking and exposure to asbestos on the development of various neoplasms].}, journal = {Wiadomosci lekarskie (Warsaw, Poland : 1960)}, volume = {39}, number = {2}, pages = {97-100}, pmid = {3524008}, issn = {0043-5147}, mesh = {Asbestos/*adverse effects ; *Cocarcinogenesis ; Dust/adverse effects ; Humans ; Mesothelioma/etiology ; Mouth Neoplasms/etiology ; Occupational Diseases/etiology ; Peritoneal Neoplasms/etiology ; Pleural Neoplasms/etiology ; Risk ; *Smoking ; }, } @article {pmid3957437, year = {1986}, author = {Woitowitz, HJ and Lange, HJ and Beierl, L and Rathgeb, M and Schmidt, K and Ulm, K and Giesen, T and Woitowitz, RH and Pache, L and Rödelsperger, K}, title = {Mortality rates in the Federal Republic of Germany following previous occupational exposure to asbestos dust.}, journal = {International archives of occupational and environmental health}, volume = {57}, number = {3}, pages = {161-171}, pmid = {3957437}, issn = {0340-0131}, mesh = {Asbestos/*adverse effects ; Environmental Exposure ; Female ; Germany, West ; Humans ; Lung Neoplasms/epidemiology ; Male ; Mesothelioma/epidemiology ; Mortality ; Neoplasms/epidemiology ; Peritoneal Neoplasms/epidemiology ; Pleural Neoplasms/epidemiology ; Prospective Studies ; }, abstract = {In 1972, a procedure was introduced by the Industrial Injuries Insurance Institutes (Berufsgenossenschaften) of the Federal Republic of Germany, which is to be used by the special occupational health service for employees exposed to asbestos dust. Since 1 January 1972, occupational health examinations are performed when exposure to asbestos dust has been of at least 3 years' duration. On 1 January 1977, a prospective cohort study was started with employees formerly exposed to asbestos dust whilst working for companies manufacturing or using asbestos. Data on these persons are collected in the Central Register of Employees Exposed to Asbestos Dust of the Industrial Injuries Insurance Institutes. A total of 3,070 male and female employees in whom asbestos exposure terminated after 1 January 1972 formed subcohort I of the study. For comparison, 665 persons whose exposure terminated before 1 January 1972 served as subcohort II. In addition to several other inclusion criteria, each individual's permission was required before personal data could be evaluated. Of the subjects in the two subcohorts, 185 and 71, respectively, had died by 31 December 1982. Tumours were more frequently than this cause of death is expected in the general population. In addition to a high incidence of mesothelioma, the standard mortality rate was especially increased for lung cancer. The proportional mortality rates of about 40% for tumours of all sites (with about 17% lung cancer and 8% mesothelioma) especially in subcohort II, seemed to be comparable to the international figures for epidemiological mortality.}, } @article {pmid3947558, year = {1986}, author = {Roggli, VL and Pratt, PC and Brody, AR}, title = {Asbestos content of lung tissue in asbestos associated diseases: a study of 110 cases.}, journal = {British journal of industrial medicine}, volume = {43}, number = {1}, pages = {18-28}, pmid = {3947558}, issn = {0007-1072}, mesh = {Aged ; Asbestos/adverse effects/*analysis ; Asbestosis/etiology/*pathology ; Female ; Humans ; Lung/*analysis ; Lung Neoplasms/etiology/*pathology ; Male ; Mesothelioma/etiology/*pathology ; Middle Aged ; Occupational Diseases/etiology ; Pleural Diseases/etiology/*pathology ; Pulmonary Fibrosis/pathology ; }, abstract = {Diseases associated with asbestos exposure include asbestosis, malignant mesothelioma, carcinoma of the lung, and parietal pleural plaques. In this study the asbestos content of lung tissue was examined in groups of cases representing each of these diseases and in several cases with non-occupational idiopathic pulmonary fibrosis. Asbestos bodies (AB), which are the hallmark of asbestos exposure, were present in the lungs of virtually everyone in the general population and present at increased levels in individuals with asbestos associated diseases. The highest numbers of AB occurred in individuals with asbestosis, all of whom had levels greater than or equal to 2000 ABs/g wet lung tissue. Every case with a content of 100,000 ABs/g or higher had asbestosis. Intermediate levels occurred in individuals with malignant mesothelioma and the lowest levels in patients with parietal pleural plaques. There was no overlap between the asbestos content of lung tissue from patients with asbestosis and those with idiopathic pulmonary fibrosis. Lung cancer was present in half the patients with asbestosis, and the distribution of histological patterns did not differ from that in patients with lung cancer without asbestosis. The asbestos body content in patients with lung cancer was highly variable. Control cases had values within our previously established normal range (0-20 ABs/g). There was a significant correlation (p less than 0.001) between AB counted by light microscope and AB and uncoated fibres counted by scanning electron microscopy. The previous observation that the vast majority of asbestos bodies isolated from human tissues have an amphibole core was confirmed.}, } @article {pmid3942156, year = {1986}, author = {Kaye, JA and Wang, AM and Joachim, CL and Seltzer, SE and Cibas, E and Skarin, A and Antman, KH}, title = {Malignant mesothelioma with brain metastases.}, journal = {The American journal of medicine}, volume = {80}, number = {1}, pages = {95-97}, doi = {10.1016/0002-9343(86)90054-9}, pmid = {3942156}, issn = {0002-9343}, mesh = {Brain/pathology ; Brain Neoplasms/diagnostic imaging/pathology/*secondary ; Humans ; Male ; Mesothelioma/diagnostic imaging/pathology/*secondary ; Middle Aged ; Pleural Neoplasms/*pathology ; Tomography, X-Ray Computed ; }, abstract = {Although malignant mesothelioma is known to spread hematogenously, brain metastases are rare. In the patient presented herein, multiple unilateral symptomatic central nervous system metastases developed that were diagnosed by computed tomography and documented at autopsy. Since malignant mesothelioma is occurring more frequently in the population at risk (asbestos workers), this complication may be observed more commonly in the future.}, } @article {pmid3823518, year = {1986}, author = {Berlin, A and Hunter, WJ and van der Venne, MT}, title = {[Epidemiology and prevention of occupational health hazards within the European Community].}, journal = {Revue d'epidemiologie et de sante publique}, volume = {34}, number = {4-5}, pages = {261-265}, pmid = {3823518}, issn = {0398-7620}, mesh = {Asbestosis/prevention & control ; Environmental Monitoring ; European Union ; Humans ; Lung Neoplasms/prevention & control ; Mesothelioma/prevention & control ; Nickel/adverse effects ; Occupational Diseases/chemically induced/etiology/*prevention & control ; Pleural Neoplasms/prevention & control ; Poison Control Centers/standards ; Risk ; Safety ; }, abstract = {Since 1978 the European Community has had an action programme on safety and health at work covering all 120 million workers in the Community. On the basis of this programme, directives (instruments of Community legislations) have been adopted by the Council of Ministers and new directives are being drafted. The aim of these directives is to improve safety at work and to protect the health of workers from mechanical, physical, chemical and biological hazards. The drafting of proposals by the Commission for presentation to the Council necessitates detailed and critical examination of the scientific data available, such as epidemiological studies, statistical data and the results of experiments. Epidemiological studies of cases of mesothelioma have led us to propose more stringent limit values for crocidolite than for other asbestos fibres in the air at the place of work. At present, in order to gain a clearer idea of the carcinogenicity of the various compounds of nickel, efforts are being made to collate and update all the epidemiological studies conducted on this subject throughout the world. Finally, particular attention is being paid to the opportunities provided by the anti-poison centres for developing clinical toxicology and epidemiology.}, } @article {pmid3822558, year = {1986}, author = {Pizzolitto, S and Barillari, B and De Cesare, M}, title = {[Diffuse malignant mesothelioma of the peritoneum and exposure to asbestos].}, journal = {Pathologica}, volume = {78}, number = {1053}, pages = {57-70}, pmid = {3822558}, issn = {0031-2983}, mesh = {Asbestosis/*complications/pathology ; Humans ; Male ; Mesothelioma/etiology/*pathology ; Middle Aged ; Peritoneal Neoplasms/etiology/*pathology ; }, } @article {pmid3765920, year = {1986}, author = {Thorn, L}, title = {[Peritoneal mesothelioma in asbestosis].}, journal = {Zentralblatt fur allgemeine Pathologie u. pathologische Anatomie}, volume = {131}, number = {6}, pages = {547-552}, pmid = {3765920}, issn = {0044-4030}, mesh = {Asbestos/adverse effects ; Asbestosis/*complications/pathology ; Humans ; Lung/pathology ; Lymph Nodes/pathology ; Male ; Mesothelioma/etiology/*pathology ; Middle Aged ; Peritoneal Neoplasms/etiology/*pathology ; }, abstract = {The clinical and pathoanatomical findings from a 46 year old man with peritoneal mesothelioma in pulmonary asbestosis are described. The tumor arose 13 years after termination of a 10 year professional exposure to asbestos dust. The findings of asbestos bodies in the hilar and tracheobronchial lymph nodes is interpreted as evidence for transport of asbestos bodies in the lymphatic vessels from the lungs to the peritoneal cavity. In the case in question, numerous histological slides showed no asbestos bodies in the tumor tissue itself. The pathogenesis of mesotheliomas following exposure to asbestos is discussed.}, } @article {pmid3757882, year = {1986}, author = {Vasil'eva, LA and Pylev, LN and Rovenskiĭ, IuA}, title = {[Study of precancerous changes in the rat pleural mesothelium following exposure to asbestos using scanning electron microscopy].}, journal = {Eksperimental'naia onkologiia}, volume = {8}, number = {4}, pages = {34-37}, pmid = {3757882}, issn = {0204-3564}, mesh = {Animals ; Asbestos/*adverse effects ; Mesothelioma/*etiology/ultrastructure ; Microscopy, Electron, Scanning ; Pleural Neoplasms/*etiology/ultrastructure ; Precancerous Conditions/*etiology/ultrastructure ; Rats ; }, abstract = {Rat pleural mesothelium was studied 16 to 22 months after intrapleural inoculation of chrysotile-asbestos. Irregular diffuse hyperplasia and focal solid and papillary pretumoral lesions were found. The morphological picture of these lesions in SEM and light microscopy have been discussed.}, } @article {pmid3742509, year = {1986}, author = {Frank, AL}, title = {Asbestos as an air pollutant and synergism with smoking.}, journal = {Cancer detection and prevention}, volume = {9}, number = {3-4}, pages = {337-341}, pmid = {3742509}, issn = {0361-090X}, mesh = {Air Pollutants/*adverse effects ; Air Pollutants, Occupational/adverse effects ; Asbestos/*adverse effects ; Female ; Humans ; Lung Neoplasms/*etiology ; Male ; Mesothelioma/*etiology ; Risk ; *Smoking ; }, abstract = {For many years the health consequences of asbestos exposure, including an overall mortality experience of approximately 50% from cancer among occupationally exposed individuals, have been well documented worldwide. Less well appreciated are the lessons to be learned from data available concerning outdoor asbestos air pollution and, of perhaps greater concern, the risks in certain indoor environments contaminated by this useful mineral. The biologically complex issue of carcinogenic synergism has been clearly demonstrated for cigarette smoking, asbestos-exposed individuals. Prevention of cancer among those exposed to asbestos not only requires efforts to minimize such exposure, but also requires strong antismoking measures among those exposed.}, } @article {pmid3740068, year = {1986}, author = {Cantor, KP and Sontag, JM and Heid, MF}, title = {Patterns of mortality among plumbers and pipefitters.}, journal = {American journal of industrial medicine}, volume = {10}, number = {1}, pages = {73-89}, doi = {10.1002/ajim.4700100109}, pmid = {3740068}, issn = {0271-3586}, mesh = {Adult ; Aged ; California ; Emphysema/mortality ; Humans ; Liver Cirrhosis/mortality ; Mesothelioma/mortality ; Middle Aged ; Neoplasms/mortality ; Occupational Diseases/*mortality ; Rheumatic Heart Disease/mortality ; *Sanitary Engineering ; }, abstract = {A proportionate mortality ratio (PMR) study was undertaken of 7,121 members and retirees of the United Association of Plumbers and Pipefitters in California who died in 1960-79. The PMR for all malignant neoplasms was 1.24, with a major contribution from lung cancers (PMR = 1.41). Lung cancer PMRs were consistently elevated, through the 20-year study period, across the pipe trades and within different birth cohorts. Sixteen mesothelioma deaths occurred, suggesting asbestos as a risk factor. PMRs for malignancies of the stomach, kidney, brain, and lymphopoietic system were also elevated, especially among plumbers. Chronic rheumatic heart disease, emphysema, liver cirrhosis, and all external causes of death were the major non-cancer causes with significantly elevated PMRs. There were significant deficits in diabetes mellitus, all pneumonia, chronic nephritis, and vascular lesions of the central nervous system (CNS). PMRs for successive birth cohorts among all study subjects revealed decreasing emphysema risk, suggesting previous reduction of a risk factor for this disease. Among plumbers, PMRs for death due to several non-respiratory malignancies showed an increasing trend with recency of birth cohort.}, } @article {pmid3720814, year = {1986}, author = {Gruber, UF}, title = {What every surgeon should know regarding asbestos-related disease.}, journal = {European surgical research. Europaische chirurgische Forschung. Recherches chirurgicales europeennes}, volume = {18}, number = {3-4}, pages = {207-212}, doi = {10.1159/000128527}, pmid = {3720814}, issn = {0014-312X}, mesh = {Asbestos/*adverse effects ; Asbestosis/pathology ; Humans ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Peritoneal Neoplasms/etiology ; Pleural Diseases/etiology ; Pleural Neoplasms/etiology ; }, abstract = {Long-lasting occupational exposure to asbestos dust may cause pleural disease, asbestosis, bronchogenic carcinoma and mesothelioma. Many years elapse from first exposure to the appearance of symptoms. Almost all these diseases are the result of dusty working conditions 20-40 years ago. The pathological sequelae are usually irreversible and can progress after exposure ceases. There is no satisfactory treatment. Prevention is the only practical way. In spite of the fact that the general public is invariably exposed to small amounts of the material, asbestos is not a public health problem. Exemptions are the buildings not properly cared for containing sprayed asbestos. But even living in such buildings is calculated to produce a negligible risk of death. Asbestos-related diseases occur where long-lasting inhalation of high amounts of fine asbestos dust has occurred. There is no evidence to indicate that ingested asbestos fibers represent a major health problem. Industry is now replacing asbestos in many products by other fibers. Natural and synthetic organic materials used in fiber cement products are unable to reach the alveoli. They are not cancerogenic and there is no reason to believe that such fibers cause chronic pulmonary disease.}, } @article {pmid3720479, year = {1986}, author = {Whitaker, D and Sterrett, G and Shilkin, K and Walters, M}, title = {Malignant mesothelioma cells in sputum.}, journal = {Diagnostic cytopathology}, volume = {2}, number = {1}, pages = {21-24}, doi = {10.1002/dc.2840020106}, pmid = {3720479}, issn = {8755-1039}, mesh = {Aged ; Asbestos/adverse effects ; Female ; Humans ; Male ; Mesothelioma/diagnosis/*pathology ; Sputum/*cytology ; }, abstract = {In five patients with malignant mesothelioma of pleura, malignant cells, presumably derived from intrapulmonary deposits, were found in sputum specimens. The cells presented mainly as papillary aggregates of epithelial-like cells, in most cases without specific identifiable mesothelial cell features. In one patient, the specimen was received early in the diagnostic work-up and led to a strong consideration of the diagnosis of adenocarcinoma. In the remainder, the finding was incidental, occurring after the diagnosis of mesothelioma had been established. The cases are reported to draw attention to this phenomenon, previously unreported in the cytologic literature, and to emphasize that the finding of malignant cells in sputum does not preclude the diagnosis of malignant mesothelioma.}, } @article {pmid3717172, year = {1986}, author = {Teirstein, AS and Chahinian, P and Goldsmith, SJ and Sorek, M}, title = {Gallium scanning in differentiating malignant from benign asbestos-related pleural disease.}, journal = {American journal of industrial medicine}, volume = {9}, number = {5}, pages = {487-494}, doi = {10.1002/ajim.4700090509}, pmid = {3717172}, issn = {0271-3586}, mesh = {Asbestosis/*diagnostic imaging ; Diagnosis, Differential ; *Gallium Radioisotopes ; Humans ; Mesothelioma/*diagnostic imaging ; Pleural Diseases/diagnostic imaging ; Pleural Neoplasms/*diagnostic imaging ; Radionuclide Imaging ; }, abstract = {In order to assess the utility of 67gallium citrate in delineating malignant pleural mesothelioma from benign asbestos-related pleural disease, 49 patients with malignant mesothelioma and 16 with benign asbestos-related pleural disease were studied. Seven patients with malignant mesothelioma had no history of asbestos exposure, while the remaining 58 patients were exposed. Forty-three of the 49 patients (88%) with malignant mesothelioma had a positive 67gallium scan including 36 of the 42 (86%) patients with asbestos exposure and all 7 patients without a history of asbestos exposure. Three of 16 patients (19%) with benign asbestos-related pleural disease had a positive scan. 67Gallium radionuclide imaging is nonspecific but may be valuable in noninvasive monitoring of asbestos-exposed populations, which have a high risk for the late development of benign and/or malignant pleural disease.}, } @article {pmid3706307, year = {1986}, author = {Mowé, G and Gylseth, B}, title = {Occupational exposure and regional variation of malignant mesothelioma in Norway, 1970-79.}, journal = {American journal of industrial medicine}, volume = {9}, number = {4}, pages = {323-332}, doi = {10.1002/ajim.4700090403}, pmid = {3706307}, issn = {0271-3586}, mesh = {Adult ; Age Factors ; Aged ; *Asbestos ; *Environmental Exposure ; Female ; Humans ; Lung/pathology ; Male ; Mesothelioma/epidemiology/*etiology/pathology ; Middle Aged ; Norway ; Occupational Diseases/epidemiology/*etiology/pathology ; Registries ; Sex Factors ; }, abstract = {This investigation is based on a study of 117 men and 24 women with malignant mesothelioma registered by the Cancer Registry of Norway, 1970-79. The age-adjusted incidence rate in men for each county varied from 1.7 to 13.3 per million per year. Eighty-two percent of the men revealed possible occupational asbestos exposure. They were evenly distributed between counties with high and low mesothelioma incidence. Only 17% of the women had possible occupational asbestos exposure. Total lung fiber concentration was analyzed with scanning electron microscopy in 65 men and 13 women. The median lung fiber concentration in men was 2.4 million per gram of dried tissue (range less than 0.4-490), in women 1.0 million per gram (range less than 0.4-41), and in male controls less than 0.4 million per gram (range less than 0.4-4.8). The median year of first exposure was 1937 (range 1909-60) for men from counties with a high incidence rate and 1945 (range 1938-59) for men from counties with a low incidence rate. The counties with a high compared to a low incidence rate of malignant mesothelioma, 1970-79, showed an apparent difference in the percentage of population employed in industry in 1946. The regional variation in the incidence of malignant mesothelioma in men is mainly attributable to the proportion of population exposed to asbestos in industry per county prior the 1950s and the time since exposure started.(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid3704398, year = {1986}, author = {Kunnert, JE and Christmann, D and Marescaux, J and Weill-Bousson, M and Pasquali, JL and Storck, D}, title = {[Malignant diffuse peritoneal mesothelioma: clinical and therapeutic aspects. Apropos of a case with gelatinous ascites].}, journal = {La Revue de medecine interne}, volume = {7}, number = {1}, pages = {78-84}, doi = {10.1016/s0248-8663(86)80088-1}, pmid = {3704398}, issn = {0248-8663}, mesh = {Ascites/etiology ; Environmental Exposure ; Humans ; Male ; Mesothelioma/*diagnosis/etiology/pathology/therapy ; Middle Aged ; Peritoneal Neoplasms/*diagnosis/etiology/pathology/therapy ; }, abstract = {Peritoneal mesothelioma ranks second in frequency after pleural mesothelioma. A well-established clinical entity since 1960, mesothelioma is increasingly frequent due to improvements in diagnostic methods and to the fairly wide industrial use of asbestos, a well-known carcinogenic substance for mesothelial cells. The diagnosis of malignant peritoneal mesothelioma rests on a corpus of convergent data. Treatment consists of surgery combined with radiotherapy and chemotherapy. The mean survival from the time of diagnosis is 8-10 months.}, } @article {pmid3542255, year = {1986}, author = {Antman, KH}, title = {Asbestos-related malignancy.}, journal = {Critical reviews in oncology/hematology}, volume = {6}, number = {3}, pages = {287-309}, doi = {10.1016/s1040-8428(86)80059-2}, pmid = {3542255}, issn = {1040-8428}, mesh = {Asbestos/*toxicity ; Asbestosis/complications ; Gastrointestinal Neoplasms/chemically induced ; Head and Neck Neoplasms/chemically induced ; Humans ; Lung Neoplasms/chemically induced ; Lymphoproliferative Disorders/chemically induced ; Mesothelioma/*chemically induced/pathology/therapy ; Neoplasms/*chemically induced ; Pleural Neoplasms/chemically induced/pathology/therapy ; Risk ; Smoking ; }, abstract = {Due to the known association with asbestos exposure, malignant mesothelioma has assumed an importance out of proportion to its incidence in the American population (2.2 per million). Patients present with chest pain, shortness of breath, or both. The initial chest X-ray generally reveals a large unilateral pleural effusion. A large piece of tissue obtained via open biopsy is usually required for histologic diagnosis. Investigational approaches include multiple needle biopsies obtained for electron microscopy, as well as for immunoperoxidase staining for keratin and CEA. The tumor characteristically remains localized until late in its course. The treatment of mesothelioma remains unsatisfactory. However, anecdotes report long-term disease-free survival after intensive treatment. Palliation with a response rate of up to 30% to various chemotherapeutic regimens has been reported by a number of investigators.}, } @article {pmid3510581, year = {1986}, author = {Hughes, JM and Weill, H}, title = {Asbestos exposure--quantitative assessment of risk.}, journal = {The American review of respiratory disease}, volume = {133}, number = {1}, pages = {5-13}, doi = {10.1164/arrd.1986.133.1.5}, pmid = {3510581}, issn = {0003-0805}, support = {HL-15092/HL/NHLBI NIH HHS/United States ; }, mesh = {*Asbestos ; Asbestosis/*complications/epidemiology ; Dose-Response Relationship, Drug ; Environmental Exposure ; Humans ; Lung Neoplasms/epidemiology/*etiology ; Mesothelioma/epidemiology/*etiology ; Risk ; Schools ; }, abstract = {Methods for deriving quantitative estimates of asbestos-associated health risks are reviewed and their numerous assumptions and uncertainties described. These methods involve extrapolation of risks observed at past relatively high asbestos concentration levels down to usually much lower concentration levels of interest today--in some cases, orders of magnitude lower. These models are used to calculate estimates of the potential risk to workers manufacturing asbestos products and to students enrolled in schools containing asbestos products. The potential risk to workers exposed for 40 yr to 0.5 fibers per milliliter (f/ml) of mixed asbestos fiber type (a permissible workplace exposure limit under consideration by the Occupational Safety and Health Administration (OSHA)) are estimated as 82 lifetime excess cancers per 10,000 exposed. The risk to students exposed to an average asbestos concentration of 0.001 f/ml of mixed asbestos fiber types for an average enrollment period of 6 school years is estimated as 5 lifetime excess cancers per one million exposed. If the school exposure is to chrysotile asbestos only, then the estimated risk is 1.5 lifetime excess cancers per million. Risks from other causes are presented for comparison; e.g., annual rates (per million) of 10 deaths from high school football, 14 from bicycling (10-14 yr of age), 5 to 20 for whooping cough vaccination. Decisions concerning asbestos products require participation of all parties involved and should only be made after a scientifically defensible estimate of the associated risk has been obtained. In many cases to date, such decisions have been made without adequate consideration of the level of risk or the cost-effectiveness of attempts to lower the potential risk.}, } @article {pmid3017103, year = {1986}, author = {Magee, F and Wright, JL and Chan, N and Lawson, L and Churg, A}, title = {Malignant mesothelioma caused by childhood exposure to long-fiber low aspect ratio tremolite.}, journal = {American journal of industrial medicine}, volume = {9}, number = {6}, pages = {529-533}, doi = {10.1002/ajim.4700090604}, pmid = {3017103}, issn = {0271-3586}, mesh = {Adult ; *Asbestos, Amphibole ; Biopsy ; Humans ; Male ; Mesothelioma/*etiology/pathology ; Microscopy, Electron ; Pleura/pathology ; Pleural Neoplasms/*etiology/pathology ; Silicic Acid/*adverse effects ; Silicon Dioxide/*adverse effects ; }, abstract = {A 41-year-old man was found to have a malignant mesothelioma of the pleura. During childhood in Corsica, he had been exposed at home to chrysotile ore from the Canari mine. Analysis of lung mineral content revealed background levels of chrysotile but an elevated level of tremolite and actinolite asbestos. The latter had a geometric mean length of 3.7 microns, a value considerably longer than we have found for tremolite and actinolite from Quebec chrysotile miners but roughly the same as the mean length of amosite and crocidolite in workers with occupational amphibole exposure. No tremolite or actinolite fibers of length greater than 8 microns microns and width less than 0.25 micron were observed. The mean aspect ratio of the tremolite and actinolite fibers was 7, a value similar to that found in chrysotile miners with mesothelioma but considerably less than the mean aspect ratio of amosite and crocidolite from those with occupational exposure. These data suggest that long-fiber tremolite is a potential mesothelial carcinogen in humans, and that fiber length is more important than fiber aspect ratio in this regard.}, } @article {pmid3008552, year = {1986}, author = {Churg, A and Wiggs, B}, title = {Fiber size and number in workers exposed to processed chrysotile asbestos, chrysotile miners, and the general population.}, journal = {American journal of industrial medicine}, volume = {9}, number = {2}, pages = {143-152}, doi = {10.1002/ajim.4700090205}, pmid = {3008552}, issn = {0271-3586}, mesh = {Air Pollutants, Occupational/*analysis ; Asbestos/*analysis ; *Asbestos, Amphibole ; Asbestos, Serpentine ; Autopsy ; Humans ; Lung/*pathology ; Male ; Middle Aged ; *Mining ; Silicic Acid/analysis ; }, abstract = {We analyzed chrysotile and chrysotile-associated amphibole (largely tremolite) asbestos fibers in 21 workers exposed to various types of processed (milled) chrysotile ore, 20 long-term chrysotile miners, and 20 members of the general population (controls). Significantly greater amounts of both chrysotile and tremolite were found in processed-ore workers and miners than in controls. On average, the mean fiber lengths and aspect ratios for the mining and processed-ore-exposed workers were similar and were significantly greater than the values seen in the controls; within the processed-ore group, there was a marked variation in these parameters, and some workers appeared to be exposed to fairly long, thin fibers. It was found empirically that the fiber size data, and to a lesser extent the concentration data, could be used to classify workers accurately into those with processed-ore exposure and controls. We conclude that fiber sizes in the lungs of processed-ore-exposed workers are similar to those of chrysotile miners and are considerably longer than those found in the general population; some processed-ore workers have longer fibers which might be responsible for higher disease incidences in certain working groups; tremolite accompanies chrysotile in a variable proportion of workers exposed to processed chrysotile products and might be important in the genesis of mesothelioma in such workers; and mineralogic analysis will usually detect exposure even when chrysotile has largely disappeared from lung tissue.}, } @article {pmid3001398, year = {1986}, author = {Hoch-Ligeti, C and Restrepo, C and Stewart, HL}, title = {Comparative pathology of cardiac neoplasms in humans and in laboratory rodents: a review.}, journal = {Journal of the National Cancer Institute}, volume = {76}, number = {1}, pages = {127-142}, pmid = {3001398}, issn = {0027-8874}, mesh = {Animals ; Animals, Laboratory ; Cricetinae ; Fibroma/pathology ; Fibrosarcoma/pathology ; Guinea Pigs ; Heart Neoplasms/*pathology/veterinary ; Hemangioendothelioma/pathology ; Hemangioma/pathology ; Histiocytoma, Benign Fibrous/pathology ; Humans ; Leukemia/pathology ; Lymphoma/pathology ; Lymphoma, Large B-Cell, Diffuse/pathology ; Lymphoma, Non-Hodgkin/pathology ; Mesenchymoma/pathology ; Mesothelioma/pathology ; Mice ; Muridae ; Myxoma/pathology ; Myxosarcoma/pathology ; Neurilemmoma/pathology ; Neurofibroma/pathology ; Osteosarcoma/pathology ; Papilloma/pathology ; Rats ; Rhabdomyoma/pathology ; Rhabdomyosarcoma/pathology ; Rodent Diseases/*pathology ; }, abstract = {This review deals with the frequency, heredity, and morphology of 19 different histologic types of cardiac tumors that may affect humans, rat, mouse, guinea pig, and mastomys. Chemicals, durable fibrous materials, viruses, and probably irradiation have induced cardiac tumors in rodents. Apart from the involvement of asbestos in the induction of pericardial mesothelioma, no carcinogens have been identified in induction or promotion of cardiac tumors in humans. A hereditary tendency for the occurrence of myxoma and aortic paraganglioma has been indicated in humans as well as strain-specific heredity for rhabdomyoma in the guinea pig and for atriocaval node tumor in the rat.}, } @article {pmid2941025, year = {1986}, author = {Weill, H and Hughes, JM}, title = {Asbestos as a public health risk: disease and policy.}, journal = {Annual review of public health}, volume = {7}, number = {}, pages = {171-192}, doi = {10.1146/annurev.pu.07.050186.001131}, pmid = {2941025}, issn = {0163-7525}, support = {HL-15092/HL/NHLBI NIH HHS/United States ; }, mesh = {Asbestos/*adverse effects ; Asbestosis/*epidemiology/prevention & control ; Construction Materials/adverse effects ; Environmental Exposure ; *Health Policy ; Humans ; Lung Neoplasms/*epidemiology/prevention & control ; Mesothelioma/*epidemiology/prevention & control ; Occupational Diseases/*epidemiology/prevention & control ; Risk ; Time Factors ; United States ; United States Occupational Safety and Health Administration ; Workers' Compensation ; }, } @article {pmid2880502, year = {1986}, author = {Seidman, H and Selikoff, IJ and Gelb, SK}, title = {Mortality experience of amosite asbestos factory workers: dose-response relationships 5 to 40 years after onset of short-term work exposure.}, journal = {American journal of industrial medicine}, volume = {10}, number = {5-6}, pages = {479-514}, doi = {10.1002/ajim.4700100506}, pmid = {2880502}, issn = {0271-3586}, mesh = {Adult ; Asbestos/*adverse effects ; Asbestos, Amosite ; Colonic Neoplasms/etiology/mortality ; Dose-Response Relationship, Drug ; Humans ; Lung Diseases/etiology/mortality ; Lung Neoplasms/etiology/mortality ; Male ; Mesothelioma/etiology/mortality ; Middle Aged ; New Jersey ; Occupational Diseases/etiology/*mortality ; Rectal Neoplasms/etiology/mortality ; Risk ; Time Factors ; }, abstract = {A cohort of 820 men in a Paterson, New Jersey, amosite asbestos factory which began work during 1941-1945 was observed from 5 to 40 years after start of work. Most of the cohort had limited duration of work experience (days, weeks, months), though some men worked for several years until the factory closed in 1954. With white males of New Jersey as the control population, Standardized Mortality Ratios (SMRs) of 500 are evident for the cohort for lung cancer and for noninfectious pulmonary diseases (including asbestosis), while being almost 300 for total cancer and about 170 for all causes of death. A statistically significant SMR of almost 200 is seen for colon-rectum cancer. Mesothelioma incidence initially shows a strong relationship with advancing time since onset of exposure and then tails off. The main concern of the study is with dose-response patterns. Response is measured by the mortality for relevant causes of death, while the direct asbestos dosage was measured in two ways. One way was the length of time worked in the factory and the other was the individual's accumulated fiber exposure, calculated by multiplying the aforementioned length of time worked by the estimated fiber exposures associated with the particular job that the worker had in the factory. Whichever measure of dosage is used, it was found that, in general, the lower the dose, the longer it took for adverse mortality to become evident and, also, the smaller the magnitude of that adverse mortality.}, } @article {pmid4096142, year = {1985}, author = {Beck, EG and Schmidt, P}, title = {Epidemiological investigations of decreased employees of the asbestos cement industry in the Federal Republic of Germany.}, journal = {Zentralblatt fur Bakteriologie, Mikrobiologie und Hygiene. 1. Abt. Originale B, Hygiene}, volume = {181}, number = {3-5}, pages = {207-215}, pmid = {4096142}, issn = {0174-3015}, mesh = {Aged ; Arteriosclerosis/mortality ; Asbestosis/*mortality ; Dust/adverse effects ; Epidemiologic Methods ; Germany, West ; Humans ; Hypertension/mortality ; Lung Neoplasms/mortality ; Mesothelioma/mortality ; Pleural Neoplasms/mortality ; Pulmonary Emphysema/mortality ; Risk ; }, abstract = {An epidemiological study of the causes of death was performed covering the entire German asbestos cement industry (10 plants). Of 376 workers who had died in the period of 1 January 1976 - 31 December 1980 and who had been employed for a minimum of 10 years, 314 were included; 307 of these were men. Special consideration was given to the asbestos-related diseases asbestosis, asbestosis in combination with lung cancer, and mesothelioma of the pleura or peritoneum. The relationship between lung cancer with asbestosis and lung cancer without asbestosis is nearly 1:1. From this the conclusion can be drawn that a causal relationship between asbestos exposure and lung cancer can be assumed in only half of the lung cancer cases. This is, however, an upper approximation, since 15 cases of lung cancer were found which is 1/3 less than the expected number in comparison with the normal population. This documents the relatively small excess (SPMR = 1.2) of all cases of lung cancer detected in the asbestos cement industry as compared to the expected lung cancer cases not due to asbestos.}, } @article {pmid3914621, year = {1985}, author = {Prentice, RL and Omenn, GS and Goodman, GE and Chu, J and Henderson, MM and Feigl, P and Kleinman, GD and Thomas, DB and Hutchinson, ML and Lund, B}, title = {Rationale and design of cancer chemoprevention studies in Seattle.}, journal = {National Cancer Institute monograph}, volume = {69}, number = {}, pages = {249-258}, pmid = {3914621}, issn = {0083-1921}, mesh = {Asbestosis/complications ; Clinical Trials as Topic ; Female ; Humans ; Lung Neoplasms/etiology/prevention & control ; Male ; Neoplasms/*prevention & control ; Random Allocation ; Research Design ; Retinoids/*therapeutic use ; Smoking ; Tretinoin/therapeutic use ; Uterine Cervical Dysplasia/pathology ; Uterine Cervical Neoplasms/prevention & control ; Washington ; }, abstract = {Three cancer prevention trials are currently in their early phases at The Fred Hutchinson Cancer Research Center, the University of Washington School of Public Health and Community Medicine, and the Swedish Hospital. All 3 studies are randomized and placebo controlled. One large-scale study involves the daily administration of retinoids to persons with asbestos-related lung disease in an attempt toward reduction of their high risk for bronchogenic carcinomas and mesotheliomas. A second study involves administration of the same agents to long-term heavy smokers; a substantial feasibility and toxicity pilot study will precede a full-scale prevention trial. In the third trial, folic acid administration is evaluated in relation to the progression and regression of cervical dysplasia among women with abnormal Pap smears. We report here the rationale and the design for these 3 studies.}, } @article {pmid3905307, year = {1985}, author = {Levine, DS}, title = {Does asbestos exposure cause gastrointestinal cancer?.}, journal = {Digestive diseases and sciences}, volume = {30}, number = {12}, pages = {1189-1198}, pmid = {3905307}, issn = {0163-2116}, support = {1PO1 AM32971-01/AM/NIADDK NIH HHS/United States ; AM07113-09/AM/NIADDK NIH HHS/United States ; }, mesh = {Adult ; Animals ; Asbestos/*adverse effects/analysis ; Cells, Cultured ; Epidemiologic Methods ; Gastrointestinal Neoplasms/*etiology ; Humans ; Male ; Occupational Diseases/*etiology ; Particle Size ; Phagocytosis ; Risk ; Water Supply ; }, abstract = {The relationship between asbestos exposure and gastrointestinal malignancies is unlike the well-established correlation between occupational asbestos exposure and the subsequent development of pleuropulmonary neoplasms and mesotheliomas. Cohort studies on occupationally exposed workers suggest an association between asbestos and gastrointestinal cancer, but evaluation of dose-response, tissue analysis, animal experiment, and cell culture data yield inconsistent conclusions. No simplistic cause-effect relationship can be ascribed to asbestos at the present time, and the answer to the question, "Does asbestos exposure cause cancer?" must await the results of additional studies.}, } @article {pmid3010925, year = {1985}, author = {Cookson, WO and De Klerk, NH and Musk, AW and Glancy, JJ and Armstrong, BK and Hobbs, MS}, title = {Benign and malignant pleural effusions in former Wittenoom crocidolite millers and miners.}, journal = {Australian and New Zealand journal of medicine}, volume = {15}, number = {6}, pages = {731-737}, pmid = {3010925}, issn = {0004-8291}, mesh = {Adult ; *Asbestos ; Asbestos, Crocidolite ; Asbestosis/*diagnosis ; Diagnosis, Differential ; Humans ; Male ; Mass Chest X-Ray ; Mesothelioma/*diagnosis ; *Mining ; Pleura/pathology ; Pleural Effusion/*diagnosis/diagnostic imaging/etiology ; Pleural Neoplasms/*diagnosis ; Regression Analysis ; Time Factors ; }, abstract = {Serial plain chest radiographs taken between 1943 and 1982 for 280 claimants for compensation for asbestosis and 32 claimants for malignant pleural mesothelioma from the Wittenoom asbestos industry were reviewed by two observers to identify diffuse pleural thickening and pleural effusion. A pleural effusion which appeared and resolved within two years without radiographic or clinical evidence of underlying malignancy, infection or cardiac failure was seen in 15 cases by reader 1 and 24 cases by reader 2. Eighteen cases of effusion, determined from clinical records to be caused by malignant pleural mesothelioma, were seen by reader 1 and 20 by reader 2. The latent periods between commencing work and the first radiograph showing effusion were much shorter for subjects with benign asbestos pleural effusion than for subjects with effusion due to malignant pleural mesothelioma, although there was considerable overlap in the range. The longest latent period for benign asbestos pleural effusion was 22 years and the shortest period for effusion due to malignant pleural mesothelioma was 12 years. The latent period for benign asbestos pleural effusion was inversely related to total cumulative exposure, whereas that for effusion due to malignant pleural mesothelioma was significantly shorter for subjects who had worked in the mill than for those who had worked in the mine. A long latent period and a history of working in the mill were significant discriminators for a malignant as opposed to a benign basis for an effusion. The appearance of a benign asbestos pleural effusion appeared to be a risk factor for the severity of subsequent diffuse pleural thickening.(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid2417365, year = {1985}, author = {Otto, H}, title = {Pathology of pleural mesothelioma.}, journal = {The Thoracic and cardiovascular surgeon}, volume = {33}, number = {6}, pages = {332-334}, doi = {10.1055/s-2007-1014160}, pmid = {2417365}, issn = {0171-6425}, mesh = {Asbestos/adverse effects ; Asbestosis/etiology ; Humans ; Mesothelioma/etiology/*pathology ; Occupational Diseases/etiology ; Pleural Neoplasms/etiology/*pathology ; Risk ; }, abstract = {Macroscopic and microscopic details of benign and malignant mesotheliomas are discussed in connection with indications for localization and frequency. Of special significance are malignant mesotheliomas of the pleura and the peritoneum resulting from exposure to asbestos which had often taken place several decades earlier. It is especially important to objectify the exposure to asbestos by means of histological and pulmonary dust investigations in those cases where the occupational anamnesis is vague or questionable.}, } @article {pmid4061248, year = {1985}, author = {DiGregorio, GJ and Kotyuk, BL}, title = {Toxicology of asbestos.}, journal = {American family physician}, volume = {32}, number = {5}, pages = {201-204}, pmid = {4061248}, issn = {0002-838X}, mesh = {Adenocarcinoma/etiology ; Asbestos/*adverse effects/metabolism ; *Asbestosis/pathology/physiopathology ; Humans ; Kinetics ; Lung Neoplasms/etiology ; Mesothelioma/etiology/pathology ; Neoplasms/*etiology ; Peritoneal Neoplasms/etiology/pathology ; Pleura/pathology ; Pleural Neoplasms/etiology/pathology ; }, } @article {pmid3834296, year = {1985}, author = {Chiappino, G and Riboldi, L and Todaro, A and Schulz, L}, title = {[Study on mesothelioma in Lombardy from 1978 to 1982].}, journal = {La Medicina del lavoro}, volume = {76}, number = {6}, pages = {454-465}, pmid = {3834296}, issn = {0025-7818}, mesh = {Asbestos/adverse effects ; Environmental Exposure ; Female ; Humans ; Italy ; Male ; Mesothelioma/*epidemiology/etiology ; Peritoneal Neoplasms/*epidemiology/etiology ; Pleural Neoplasms/*epidemiology/etiology ; }, } @article {pmid4060030, year = {1985}, author = {Falkson, CI}, title = {Mesothelioma or ovarian carcinoma? A case report.}, journal = {South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde}, volume = {68}, number = {9}, pages = {676-677}, pmid = {4060030}, issn = {0256-9574}, mesh = {Carcinoma, Papillary/*diagnosis ; Diagnosis, Differential ; Female ; Humans ; Mesothelioma/*diagnosis ; Middle Aged ; Ovarian Neoplasms/*diagnosis ; }, abstract = {Ovarian carcinomas and malignant mesotheliomas are related neoplasms. Embryologically both are derived from coelomic epithelial cells and both can be related to asbestos exposure. Furthermore, histological differentiation between these two tumours can be confusing. However, distinguishing between these tumours is important because their treatment and prognosis are not the same. Ovarian carcinomas respond to chemotherapy with rates from 40% to 75%; malignant mesotheliomas are not sensitive to chemotherapy and response rates are poor.}, } @article {pmid4085437, year = {1985}, author = {McDonald, JC}, title = {Health implications of environmental exposure to asbestos.}, journal = {Environmental health perspectives}, volume = {62}, number = {}, pages = {319-328}, pmid = {4085437}, issn = {0091-6765}, mesh = {Asbestos/*adverse effects ; Drinking ; *Environmental Exposure ; Female ; Health Surveys ; Housing ; Humans ; Lung Neoplasms/etiology ; Male ; Mesothelioma/etiology ; Microclimate ; Mining ; Neoplasms/*etiology/mortality ; Registries ; Risk ; Sex Factors ; United States ; Water Supply ; }, abstract = {The health impact of environmental pollution resulting from the industrial use of asbestos can be assessed in three ways. First, there are the direct epidemiological surveys. These indicate that domestic exposure has been responsible for cases of mesothelioma and possibly lung cancer and radiological changes in family contacts of asbestos workers. Exposure in the neighborhood of crocidolite mines and factories has also resulted in cases of mesothelioma but no similar evidence exists for chrysotile or amosite. Neither air nor water pollution has been directly incriminated as a cause of either respiratory or digestive malignancies. Second, a few attempts have been made to extrapolate from exposure response findings in industrial cohorts. For several reasons, even for lung cancer, this approach is dubious: the observed gradients have a 100-fold range in slope; the equivalences of dust, fiber and gravimetric measures are largely guesswork; and the carcinogenic potential of mineral fibers, particularly for the pleura, varies enormously with fiber type and/or dimensions. No adequate exposure-response observations have been made for mesothelioma. A third approach makes use of the differing incidence of mesothelioma in men and women. Data from several countries indicate that, until the 1950s (i.e., 30-40 years after significant industrial use of asbestos began), the rates were similar in both sexes. Since then, the incidence in males has risen steeply--in the U.S. and U.K. at about 10% per annum. In females, on the other hand, there has been little or no convincing increase. These data suggest that the "background" level of mesothelioma in both sexes is and has been about 2 per million per annum and that--as at least some mesothelioma cases in females are directly or indirectly attributable to occupational exposure--there is little room left for any contribution from the general environment. It is recommended that mesothelioma surveillance, backed by appropriate epidemiological inquiries, offers an effective method of monitoring the health impact of asbestos air pollution.}, } @article {pmid4076793, year = {1985}, author = {Pylev, LN and Kulagina, TF and Kogan, FM}, title = {[Role of zirconium and citric acid complex in the development of asbestos-induced pleural blastoma].}, journal = {Gigiena truda i professional'nye zabolevaniia}, volume = {}, number = {10}, pages = {53-55}, pmid = {4076793}, issn = {0016-9919}, mesh = {Animals ; Asbestosis/*complications ; Citrates/*adverse effects ; Citric Acid ; *Cocarcinogenesis ; Female ; Male ; Mesothelioma/*etiology ; Pleural Neoplasms/*etiology ; Rats ; Zirconium/*adverse effects ; }, } @article {pmid4073386, year = {1985}, author = {Kotin, P}, title = {Asbestosis.}, journal = {The Alabama journal of medical sciences}, volume = {22}, number = {4}, pages = {388-391}, pmid = {4073386}, issn = {0002-4252}, mesh = {Asbestos/adverse effects ; Asbestosis/*etiology/pathology ; Humans ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Respiratory System/pathology ; }, } @article {pmid4070164, year = {1985}, author = {Paur, R and Woitowitz, HJ and Rödelsperger, K and John, H}, title = {[Pleural mesothelioma following asbestos exposure during brake repairs in the automobile trade: case report].}, journal = {Praxis und Klinik der Pneumologie}, volume = {39}, number = {10}, pages = {362-366}, pmid = {4070164}, issn = {0342-7498}, mesh = {Adult ; Asbestosis/*etiology ; Automobiles ; Humans ; Male ; Mesothelioma/*etiology ; Middle Aged ; Pleural Neoplasms/*etiology ; }, } @article {pmid4042277, year = {1985}, author = {Feron, VJ and Scherrenberg, PM and Immel, HR and Spit, BJ}, title = {Pulmonary response of hamsters to fibrous glass: chronic effects of repeated intratracheal instillation with or without benzo[a]pyrene.}, journal = {Carcinogenesis}, volume = {6}, number = {10}, pages = {1495-1499}, doi = {10.1093/carcin/6.10.1495}, pmid = {4042277}, issn = {0143-3334}, mesh = {Animals ; Asbestos ; Benzo(a)pyrene/*pharmacology ; Cricetinae ; *Glass ; Granuloma/etiology/pathology ; Lung/*drug effects ; Male ; Mesocricetus ; Silicosis/*etiology/pathology ; Time Factors ; }, abstract = {Syrian golden hamsters were given intratracheal instillations of glass fibres with or without benzo[a]pyrene suspended in saline, once a fortnight for 52 weeks. The experiment was terminated at week 85. 'Silicotic granulomas' consisting of tightly packed, iron-positive macrophages filled with glass fibres and surrounded by a layer of alveolar epithelial cells were the predominant pulmonary lesion. No mesotheliomas or other tumours of the respiratory tract were observed in hamsters treated with glass fibres alone. There was no indication that glass fibres enhanced the development of respiratory tract tumours induced by benzo[a]pyrene. In hamsters similarly exposed to crocidolite fibres with or without benzo[a]pyrene no mesotheliomas or other respiratory tract tumours were observed either. An explanation for the absence of pulmonary tumours might be that repeated administration of fibres over a period of 52 weeks entails an acute pulmonary reaction after each administration with the implication that the fibres cannot settle down well enough to be able to induce tumours. Another possible explanation is the relatively short duration of the experimental period.}, } @article {pmid2862294, year = {1985}, author = {Fischbein, A and Langer, AM and Rohl, AN}, title = {Asbestos-associated diseases: lessons from the past for the future.}, journal = {JAMA}, volume = {254}, number = {10}, pages = {1309-1310}, pmid = {2862294}, issn = {0098-7484}, mesh = {Asbestos/*adverse effects ; Asbestos, Amosite ; Humans ; Male ; Mesothelioma/*etiology ; Pleural Neoplasms/*etiology ; }, } @article {pmid4033487, year = {1985}, author = {Xu, Z and Armstrong, BK and Blundson, BJ and Rogers, JM and Musk, AW and Shilkin, KB}, title = {Trends in mortality from malignant mesothelioma of the pleura, and production and use of asbestos in Australia.}, journal = {The Medical journal of Australia}, volume = {143}, number = {5}, pages = {185-187}, pmid = {4033487}, issn = {0025-729X}, mesh = {Adult ; Asbestos/*adverse effects ; Australia ; Commerce ; Female ; Humans ; Industry ; Male ; Mesothelioma/etiology/*mortality ; Pleural Neoplasms/etiology/*mortality ; Sex Factors ; Time Factors ; }, abstract = {Annual mortality from malignant mesothelioma of the pleura (MMP) in Australia (as represented by ICD8 codes 163.0 and 212.4, and ICD9 codes 163 and 212.4) increased in men aged 30 years and older from about 0.5/100 000 in 1968-1970 to 2.1/100 000 in 1983. Corresponding rates in women varied from 0.1/100 000 to 0.2/100 000 between 1968 and 1980, then rose to 0.3/100 000 in 1983. The rise in MMP mortality in men probably corresponds to the increasing use of asbestos, particularly amosite, in Australia during and after World War II. That production and importation of amosite and crocidolite in Australia reached a peak in 1958 may mean that peak mortality from MMP will not be reached until the 1990s (allowing a 35-year lag period). Substantial increases in importation and later production, of chrysotile in the 1950s, 1960s and 1970s may lead to increases in the incidence of other asbestos-related cancers, not reflected in trends in the incidence of MMP.}, } @article {pmid4029409, year = {1985}, author = {Abratt, RP and Willcox, PA and Casserley, RD and Uys, CJ}, title = {Mesothelioma--short latent period after industrial asbestos exposure and prolonged survival.}, journal = {European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology}, volume = {11}, number = {3}, pages = {279-282}, pmid = {4029409}, issn = {0748-7983}, mesh = {Adult ; Air Pollutants, Occupational/adverse effects ; Asbestos/*adverse effects ; Humans ; Lymphatic Metastasis/pathology ; Male ; Mesothelioma/*etiology/pathology ; Peritoneal Neoplasms/*etiology/pathology ; Peritoneum/pathology ; Pleura/pathology ; Pleural Effusion/etiology ; Pleural Neoplasms/pathology/*secondary ; Radiography, Thoracic ; }, } @article {pmid4016698, year = {1985}, author = {Mowé, G and Gylseth, B and Hartveit, F and Skaug, V}, title = {Fiber concentration in lung tissue of patients with malignant mesothelioma. A case-control study.}, journal = {Cancer}, volume = {56}, number = {5}, pages = {1089-1093}, doi = {10.1002/1097-0142(19850901)56:5<1089::aid-cncr2820560522>3.0.co;2-y}, pmid = {4016698}, issn = {0008-543X}, mesh = {Adult ; Aged ; Asbestos/*adverse effects/analysis ; Female ; Humans ; Lung/*analysis ; Male ; Mesothelioma/*etiology/metabolism ; Middle Aged ; Norway ; Occupational Diseases/*etiology/metabolism ; Pleural Neoplasms/*etiology/metabolism ; Probability ; Risk ; }, abstract = {The risk of malignant mesothelioma associated with low-level asbestos exposure is an important unresolved issue today. We have analyzed the asbestos fiber concentration in lung tissue from 14 cases of malignant mesothelioma and 28 case-matched controls by scanning electron microscopy. The cases represent 86% of all mesotheliomas recorded by the Cancer Registry of Norway from the county of Hordaland between 1970 and 1979. Based on 1 million fibers per g of dried tissue as an indicator of cumulated asbestos exposure, the odds ratio (relative risk) was 8.5 (95% confidence limits, 2.3-31.1). Assuming that the risk of malignant mesothelioma is related to mineral fiber concentration in lung tissue, it is concluded that a fiber concentration exceeding 1 million fibers per g of dried tissue is associated with an increased risk of malignant mesothelioma. Furthermore, the results are consistent with a no-threshold response.}, } @article {pmid4016758, year = {1985}, author = {Kolonel, LN and Yoshizawa, CN and Hirohata, T and Myers, BC}, title = {Cancer occurrence in shipyard workers exposed to asbestos in Hawaii.}, journal = {Cancer research}, volume = {45}, number = {8}, pages = {3924-3928}, pmid = {4016758}, issn = {0008-5472}, support = {1 NO1 CA 15655/CA/NCI NIH HHS/United States ; N01 CN 53511/CN/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Hawaii ; Humans ; Male ; Mesothelioma/epidemiology ; Middle Aged ; Neoplasms/*epidemiology ; Occupational Diseases/*epidemiology ; Risk ; *Ships ; Smoking ; Time Factors ; }, abstract = {Because large numbers of persons were employed in United States shipyards during World War II, the long-term risks for cancer associated with asbestos exposure in this setting are of great concern. We report here on the mortality findings after up to 29 years of follow-up on a retrospective cohort of 7971 male Pearl Harbor Naval Shipyard workers, which included more than 3000 men whose employment period spanned the World War II years. Compared with the general population of Hawaii, workers in the shipyard cohort had no increase in total mortality or in total cancer mortality irrespective of the duration of their exposure. However, the risk ratio for lung cancer among workers with at least 15 years of asbestos exposure was 1.4 overall (95% confidence interval, 1.0 to 2.0) and 1.7 for those with a latency interval of 30 or more years (95% confidence interval, 1.0 to 2.5). In addition, seven mesotheliomas occurred between 1977 and 1982 in a subset of the cohort, consisting of 7029 Hawaii residents who are being followed prospectively for cancer incidence. This represented an incidence of 67.3 per million men per year, compared with a rate of 5.8 for the state as a whole. These results suggest that the long-term relative increase in risk for mesothelioma may be even greater than that for bronchogenic carcinoma in this and other cohorts of United States shipyard workers exposed to asbestos.}, } @article {pmid4016012, year = {1985}, author = {McDonald, AD and McDonald, JC}, title = {Mesothelioma and asbestos fibre type.}, journal = {British journal of industrial medicine}, volume = {42}, number = {8}, pages = {567-568}, pmid = {4016012}, issn = {0007-1072}, mesh = {Asbestos/*adverse effects ; Female ; Humans ; Male ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; }, } @article {pmid4016008, year = {1985}, author = {Solomon, SJ and Fischbein, A and Sharma, OK and Borek, E}, title = {Modified nucleosides in asbestos workers at high risk of malignant disease: results of a preliminary study applying discriminant analysis.}, journal = {British journal of industrial medicine}, volume = {42}, number = {8}, pages = {560-562}, pmid = {4016008}, issn = {0007-1072}, mesh = {Adult ; Asbestos/*adverse effects ; Humans ; Male ; Mesothelioma/diagnosis/etiology ; Middle Aged ; Nucleosides/*urine ; Occupational Diseases/*diagnosis/etiology ; Pilot Projects ; Precancerous Conditions/*diagnosis/etiology ; Risk ; }, abstract = {Patients with asbestos related malignant mesothelioma excrete high levels of modified nucleosides in their urine. The purpose of the present report was to explore further the usefulness of measuring these breakdown products of transfer RNA (tRNA) in male asbestos insulation workers who are at high neoplastic risk but without clinical signs of malignancy. Modified nucleoside levels (psi, m'A, m'I, m2G, and ac4C) were used as discriminator variables in a computer generated discriminant function in which 96% of the controls and 95% of the insulation workers were correctly classified. It was also found, using a similar multiple regression model, that 10 of 13 were correctly classified as having normal chest radiographs and 27 of 30 asbestos exposed subjects as exhibiting alterations in either the parenchyma, pleura, or both. The results suggest that measuring modified nucleosides levels in the urine of asbestos exposed workers, and perhaps others exposed to carcinogenic agents, has the potential for identifying, through multivariate statistical techniques, individuals who are at high neoplastic risk.}, } @article {pmid2988741, year = {1985}, author = {Anderson, KA and Hurley, WC and Hurley, BT and Ohrt, DW}, title = {Malignant pleural mesothelioma following radiotherapy in a 16-year-old boy.}, journal = {Cancer}, volume = {56}, number = {2}, pages = {273-276}, doi = {10.1002/1097-0142(19850715)56:2<273::aid-cncr2820560212>3.0.co;2-0}, pmid = {2988741}, issn = {0008-543X}, mesh = {Adolescent ; Humans ; Kidney Neoplasms/radiotherapy ; Lung Neoplasms/prevention & control/radiotherapy ; Male ; Mesothelioma/*etiology/surgery/ultrastructure ; Pleural Neoplasms/*etiology/surgery/ultrastructure ; Radiotherapy/*adverse effects ; Time Factors ; Wilms Tumor/radiotherapy ; }, abstract = {A case of diffuse, epithelioid mesothelioma of the right pleura in a 16-year-old boy is presented. Though a history of previous exposure to asbestos could not be elicited, the patient did receive pulmonary irradiation for metastatic Wilms' tumor at the age of 2 years. The authors believe that the development of his mesothelioma was causally related to his prior radiotherapy.}, } @article {pmid4079109, year = {1985}, author = {Nishijo, M and Momonoya, I and Teranishi, H and Kasuya, M and Kitagawa, M}, title = {[A case of mesothelioma in a part-time farmer exposed to asbestos].}, journal = {Sangyo igaku. Japanese journal of industrial health}, volume = {27}, number = {4}, pages = {258-259}, doi = {10.1539/joh1959.27.258}, pmid = {4079109}, issn = {0047-1879}, mesh = {Agriculture ; Asbestos/*adverse effects ; Humans ; Male ; Mesothelioma/*etiology ; Middle Aged ; Occupational Diseases/*etiology ; Pleural Neoplasms/*etiology ; }, } @article {pmid4015250, year = {1985}, author = {Gaensler, EA and McLoud, TC and Carrington, CB}, title = {Thoracic surgical problems in asbestos-related disorders.}, journal = {The Annals of thoracic surgery}, volume = {40}, number = {1}, pages = {82-96}, doi = {10.1016/s0003-4975(10)61179-4}, pmid = {4015250}, issn = {0003-4975}, support = {HL 1173/HL/NHLBI NIH HHS/United States ; HL 19717/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Asbestosis/surgery ; Carcinoma, Bronchogenic/surgery ; Female ; Follow-Up Studies ; Humans ; Lung Diseases/diagnostic imaging/etiology/*surgery ; Lung Neoplasms/surgery ; Male ; Mesothelioma/surgery ; Middle Aged ; Pleural Diseases/diagnostic imaging/etiology/*surgery ; Pleural Effusion/surgery ; Pleural Neoplasms/surgery ; *Population Surveillance ; Pulmonary Fibrosis/surgery ; Radiography ; Recurrence ; Time Factors ; United States ; }, abstract = {Among 1,577 persons with asbestos exposure followed up from 3 to 30 years, 113 had thoracic surgical procedures for asbestos-related disorders. Twenty-six individuals suspected of having asbestosis with atypical features underwent open-lung biopsy; a different disease was revealed in 14. Most of the 29 patients with mesothelioma had a small thoracotomy for diagnosis only; chemotherapy in half of them proved entirely ineffective. Experience with 23 patients with bronchogenic carcinoma did not differ from that in persons not exposed to asbestos. Problems of causal relationship are discussed. Most of the 68 individuals with benign asbestos pleural effusion had no symptoms, but because of recurrence, 15 were operated on for decortication or for possible mesothelioma. Hyaline plaques often were mistaken for lung, rib, or diaphragmatic tumors, and sometimes mesothelioma was suspected. Operative intervention in the 24 patients with plaques could have been avoided by obtaining a more detailed occupational history and reviewing previous chest roentgenograms, which invariably showed identical or smaller plaques from 2 to 17 years earlier.}, } @article {pmid3836085, year = {1985}, author = {Greenberg, SD}, title = {Cytopathology of asbestos-associated pulmonary disease.}, journal = {Diagnostic cytopathology}, volume = {1}, number = {3}, pages = {177-182}, doi = {10.1002/dc.2840010304}, pmid = {3836085}, issn = {8755-1039}, support = {HL-29542/HL/NHLBI NIH HHS/United States ; }, mesh = {Asbestos/*adverse effects/analysis ; Asbestosis/pathology ; Bronchi/pathology ; Carcinoma/pathology ; Cytodiagnosis ; Humans ; Lung Diseases/etiology/*pathology ; Lung Neoplasms/*pathology ; Mesothelioma/pathology ; Sputum/cytology ; }, abstract = {The goal of this investigation was to determine the practical role of cytopathology in the clinical and laboratory diagnosis of asbestos-related pulmonary diseases. For this purpose, sputum, bronchial washings, lung tissues, and pleural fluids were obtained from asbestos workers and controls. The asbestos-associated pulmonary diseases studied were: (1) asbestosis, (2) carcinoma, and (3) mesothelioma. The cytology smears were prepared with both Papanicolaou and iron stains. Lung tissues were digested by the Chlorox (5.25% sodium hypochlorite solution) technique for quantitation of asbestos bodies. Asbestos bodies within the sputum were found to be highly specific markers for past asbestos exposure, indicating a heavy residual pulmonary asbestos load (greater than 900 asbestos bodies/g wet lung weight). Asbestos bodies in sputum were also found to have a highly significant relationship (P less than 0.001) with the degree of accompanying atypia of bronchial epithelial cells. Bronchial washings appeared to be more sensitive than sputum for the detection of asbestos bodies. Asbestos bodies were not found within the pleural fluids of malignant mesotheliomas. It is concluded that sputum cytology screening represents a practical, noninvasive, and inexpensive approach to the diagnosis and study of asbestos exposure.}, } @article {pmid2990524, year = {1985}, author = {Cookson, WO and Musk, AW and Glancy, JJ and de Klerk, NH and Yin, R and Mele, R and Carr, NG and Armstrong, BK and Hobbs, MS}, title = {Compensation, radiographic changes, and survival in applicants for asbestosis compensation.}, journal = {British journal of industrial medicine}, volume = {42}, number = {7}, pages = {461-468}, pmid = {2990524}, issn = {0007-1072}, mesh = {Asbestos/adverse effects ; Asbestos, Crocidolite ; Asbestosis/diagnostic imaging/*mortality ; Australia ; Disability Evaluation ; Humans ; Male ; Radiography ; Time Factors ; *Workers' Compensation ; }, abstract = {The survival of 354 claimants for compensation for pulmonary asbestosis among former workers of the Wittenoom crocidolite mine and mill in Western Australia has been examined. There were 118 deaths up to December 1982. The median time between start of work and claim for compensation was 17 years. The standardised mortality ratio (SMR) for deaths from all causes was 2.65 (p less than 0.0001). The SMR for pneumoconiosis was 177.2 (p less than 0.0001), bronchitis and emphysema 2.6 (p = 0.04), tuberculosis 44.6 (p less than 0.0001), respiratory cancer (including five deaths from malignant pleural mesothelioma) 6.4 (p less than 0.0001), gastrointestinal cancer 1.6 (p = 0.22), all other cancers 1.6 (p = 0.17), heart disease 1.4 (p = 0.07), and all other causes 2.18 (p = 0.004). Plain chest radiographs taken within two years of claiming compensation were found for 238 subjects and were categorised independently by two observers according to the International Labour Organisation criteria without knowledge of exposure or compensation details. Profusion of radiographic opacities, age at claiming compensation, work in the Wittenoom mill, and degree of disability awarded by the pneumoconiosis medical board were significant predictors of survival, but total estimated exposure to asbestos was not. Radiographic profusion and degree of disability were, however, predictable by total exposure. The median survival from claim for compensation was 17 years in subjects with ILO category 1 pneumoconiosis, 12 years in category 2, and three years in category 3.}, } @article {pmid4003623, year = {1985}, author = {Kilburn, KH and Lilis, R and Anderson, HA and Boylen, CT and Einstein, HE and Johnson, SJ and Warshaw, R}, title = {Asbestos disease in family contacts of shipyard workers.}, journal = {American journal of public health}, volume = {75}, number = {6}, pages = {615-617}, pmid = {4003623}, issn = {0090-0036}, mesh = {Adolescent ; Adult ; Asbestos/adverse effects ; Asbestosis/diagnostic imaging/epidemiology/*etiology ; California ; Environmental Exposure ; *Family ; Female ; Humans ; Male ; Michigan ; Middle Aged ; Radiography ; Risk ; Surveys and Questionnaires ; Time Factors ; }, abstract = {Radiologic signs of pulmonary asbestos disease were found in 11.3 per cent of 274 wives of shipyard workers who were 20 or more years from initial hiring-on in shipyards in Los Angeles County. Asbestosis was also found in 7.6 per cent of 79 sons and 2.1 per cent of 140 daughters of these workers. The wives, sons, and daughters were without occupational exposure. Comparable radiographic signs were not found in comparison groups. It is probable that asbestos exposure in the household places these family members at risk for mesothelioma and lung cancer.}, } @article {pmid2987952, year = {1985}, author = {Lechner, JF and Tokiwa, T and LaVeck, M and Benedict, WF and Banks-Schlegel, S and Yeager, H and Banerjee, A and Harris, CC}, title = {Asbestos-associated chromosomal changes in human mesothelial cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {82}, number = {11}, pages = {3884-3888}, pmid = {2987952}, issn = {0027-8424}, mesh = {Asbestos/*toxicity ; Asbestos, Serpentine ; *Chromosomes, Human ; Humans ; Karyotyping ; Lung/*ultrastructure ; Lung Neoplasms/genetics/*ultrastructure ; Mesothelioma/genetics/*ultrastructure ; Microscopy, Electron, Scanning ; Phagocytosis ; *Pleural Effusion ; }, abstract = {Replicative cultures of human pleural mesothelial cells were established from noncancerous adult donors. The cells exhibited normal mesothelial cell characteristics including keratin, hyaluronic acid mucin, and long branched microvilli, and they retained the normal human karyotype until senescence. The mesothelial cells were 10 and 100 times more sensitive to the cytotoxic effects of asbestos fibers than normal human bronchial epithelial or fibroblastic cells, respectively. In addition, cultures of mesothelial cells that survived two cytotoxic exposures of amosite fibers were aneuploid with consistent specific chromosomal losses indicative of clonal origin. These aneuploid cells exhibit both altered growth control properties and a population doubling potential of greater than 50 divisions beyond the culture life span (30 doublings) of the control cells.}, } @article {pmid4047149, year = {1985}, author = {Seidman, H}, title = {Age at exposure versus years of exposure.}, journal = {National Cancer Institute monograph}, volume = {67}, number = {}, pages = {205-209}, pmid = {4047149}, issn = {0083-1921}, mesh = {Adult ; *Age Factors ; Aged ; Asbestos/adverse effects ; Female ; Humans ; Lung Neoplasms/mortality ; Male ; Mesothelioma/epidemiology ; Middle Aged ; Neoplasms/*epidemiology ; Pleural Neoplasms/epidemiology ; Prospective Studies ; Risk ; Smoking ; Statistics as Topic ; Time Factors ; }, abstract = {The pattern of incidence rates according to age for many forms of cancer has been found to be in reasonable accord with the equation or some modification of it: It = btk, where It is the incidence rate at age t, and b and k are constants. An alternative equation postulates that the risk of cancer is determined not by the age of a person but by the length of time exposed to a carcinogenic agent: It = b(t-w)k, where t-w represents the "effective exposure" between first exposure and clinical evidence of cancer. Mesothelioma rates in asbestos insulation workers were strongly related to time from onset of exposure regardless of age at first exposure. However, the same pattern was not evident for lung cancer mortality in the same workers compared with blue collar worker controls from the American Cancer Society Cancer Prevention Study I. Lung cancer mortality by attained rates and by duration of smoking were shown for current smokers of cigarettes only for the Cancer Society study, classified by age at which they started smoking. Lung cancer results were also given for men who never smoked regularly.}, } @article {pmid4047139, year = {1985}, author = {Nicholson, WJ}, title = {Selection factors in cohort studies.}, journal = {National Cancer Institute monograph}, volume = {67}, number = {}, pages = {111-115}, pmid = {4047139}, issn = {0083-1921}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Female ; Humans ; Leukemia, Radiation-Induced/*epidemiology ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Occupational Diseases/*epidemiology ; Prospective Studies ; Risk ; Statistics as Topic ; }, abstract = {Cohort studies play an important role in the quantitation of cancer risk among occupationally exposed individuals. Properly conducted cohort studies can develop important data on the age, time, and exposure dependence of cancer risk. Such information allows identification of possible selection effects which may be present and allows generalization of risk estimates to other exposure circumstances.}, } @article {pmid4029785, year = {1985}, author = {Ben-Dror, G and Suprun, H and Shkolnik, T}, title = {[Peritoneal mesotheliomas and exposure to asbestos].}, journal = {Harefuah}, volume = {108}, number = {9}, pages = {435-437}, pmid = {4029785}, issn = {0017-7768}, mesh = {Adult ; Asbestos/*adverse effects ; Ascites/diagnosis ; Humans ; Male ; Mesothelioma/*diagnosis/etiology/pathology ; Middle Aged ; Occupational Diseases/*etiology ; Peritoneal Neoplasms/*diagnosis/etiology/pathology ; }, } @article {pmid4000580, year = {1985}, author = {Ewing, WM and Spain, WH and Clay, EM and Bosserman, FC}, title = {Variety of asbestos uses requires many different substitute materials.}, journal = {Occupational health & safety (Waco, Tex.)}, volume = {54}, number = {5}, pages = {42-47}, pmid = {4000580}, issn = {0362-4064}, mesh = {Asbestos/*adverse effects ; Asbestosis/*prevention & control ; Construction Materials/adverse effects ; Humans ; Lung Neoplasms/prevention & control ; Mesothelioma/prevention & control ; }, } @article {pmid3994913, year = {1985}, author = {Andersson, M and Olsen, JH}, title = {Trend and distribution of mesothelioma in Denmark.}, journal = {British journal of cancer}, volume = {51}, number = {5}, pages = {699-705}, pmid = {3994913}, issn = {0007-0920}, mesh = {Adult ; Aged ; Denmark ; Female ; Humans ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Peritoneal Neoplasms/epidemiology ; Pleural Neoplasms/epidemiology ; Residence Characteristics ; Risk ; Sex Factors ; }, abstract = {The time trend and the distribution of malignant mesothelioma in Denmark are described on the basis of all notifications of cancer cases to the Danish Cancer Registry during the period 1943-1980. The age and sex adjusted incidence rates of pleural as well as peritoneal mesothelioma are increasing with time and reached in the latest 3-year registration period 1978-1980 a remarkably high total incidence of 14.7 cases per million men and 7.0 cases per million women. Towards the end of the observation period, however, the rate of increase was stagnating and for the younger age-groups even a fall in incidence of this malignancy was noted, perhaps reflecting the introduction of compulsory hygienic precautions in the handling of asbestos in Denmark. The incidence and time trend of peritoneal mesothelioma was similar among males and females while pleural mesothelioma was three times more common among males compared with females and showed an increase in incidence 15 years previous to females. For pleural mesothelioma in men notified through the 10-year period 1968, 1977, a significant excess was associated with residence in areas with high degrees of urbanization and in ship building towns.}, } @article {pmid3845816, year = {1985}, author = {Finkelstein, MM}, title = {A study of dose-response relationships for asbestos associated disease.}, journal = {British journal of industrial medicine}, volume = {42}, number = {5}, pages = {319-325}, pmid = {3845816}, issn = {0007-1072}, mesh = {Adolescent ; Adult ; Asbestos/*adverse effects ; Calcium Hydroxide ; Canada ; Chemical Industry ; Dose-Response Relationship, Drug ; Humans ; Lung Diseases/*etiology ; Lung Neoplasms/etiology ; Male ; Mesothelioma/etiology ; Models, Biological ; Occupational Diseases/*etiology ; Risk ; Smoking ; }, abstract = {The risk of an asbestos worker developing small irregular opacities on the chest radiograph is related to cumulative exposure to asbestos dust, latency, and smoking habit. In this study the use of residence-time weighted exposure as a "dose metric" was explored in a cohort of asbestos cement workers. It was found that this parameter, which incorporates both exposure concentration and latency, is useful for modelling the risk of small opacities and might also be useful for modelling the risk of mesothelioma.}, } @article {pmid2988806, year = {1985}, author = {Davis, JM and Addison, J and Bolton, RE and Donaldson, K and Jones, AD and Miller, BG}, title = {Inhalation studies on the effects of tremolite and brucite dust in rats.}, journal = {Carcinogenesis}, volume = {6}, number = {5}, pages = {667-674}, doi = {10.1093/carcin/6.5.667}, pmid = {2988806}, issn = {0143-3334}, mesh = {Air Pollutants, Occupational/toxicity ; Animals ; Asbestos/analysis ; *Asbestos, Amphibole ; Asbestos, Serpentine ; Body Burden ; Dust/*adverse effects ; Injections, Intraperitoneal ; Lung/pathology ; Lung Neoplasms/chemically induced ; Magnesium/*toxicity ; Magnesium Hydroxide/*toxicity ; Male ; Microscopy, Electron, Scanning ; Rats ; Rats, Inbred Strains ; Silicic Acid/*toxicity ; Silicon Dioxide/*toxicity ; }, abstract = {Samples of commercially used asbestos, especially chrysotile, are frequently contaminated by small amounts of other fibrous minerals. Among these are tremolite and brucite although pure tremolite is also produced commercially in relatively small quantities. In order to determine how harmful commercially exploited tremolite might be in comparison with other asbestos types and to explore the possibility that small amounts of tremolite and brucite as contaminants could significantly affect the pathogenicity of industrially used chrysotile, long-term animal inhalation and injection studies using rats were undertaken with what were considered to be mineralogically pure samples of these minerals. Rats treated with tremolite developed very high levels of pulmonary fibrosis as well as 16 carcinomas and two mesotheliomas in a group of 39 animals. Tremolite thus proved to be the most dangerous mineral that we have studied. Animals treated with 'brucite' developed moderate levels of pulmonary fibrosis and two carcinomas. Both tremolite and brucite produced mesotheliomas in greater than 90% of animals following i.p. injection. However, it was found that the supposedly pure brucite in fact contained 10% chrysotile, a level of contamination that could well have been responsible for the pathological changes found in both inhalation and intraperitoneal injection studies. The greatest care should be exercised by industry in handling tremolite or materials contaminated with it.}, } @article {pmid2986668, year = {1985}, author = {Wagner, JC and Skidmore, JW and Hill, RJ and Griffiths, DM}, title = {Erionite exposure and mesotheliomas in rats.}, journal = {British journal of cancer}, volume = {51}, number = {5}, pages = {727-730}, pmid = {2986668}, issn = {0007-0920}, mesh = {Aluminum Silicates/*toxicity ; Animals ; Asbestos/toxicity ; Asbestos, Crocidolite ; Asbestos, Serpentine ; Female ; Male ; Mesothelioma/*chemically induced ; Pleural Neoplasms/chemically induced ; Rats ; Rats, Inbred F344 ; Zeolites ; }, abstract = {Epidemiological and environmental surveys in the Cappadocian region of Turkey have linked the high incidence of pleural and peritoneal mesothelioma in the occupants of some villages with the zeolite fibres released from the locally occurring volcanic tuff. In view of the low ambient fibre concentrations and the extraordinary incidence of mesothelioma a study to test the hypothesis of high biological activity for the zeolite fibres was required. Experimental studies using both intrapleural inoculation and inhalation techniques have been undertaken with the erionite from this region and from Oregon in the United States. Additionally a non-fibrous zeolite from Japan and a synthetic non-fibrous zeolite of similar chemical composition to erionite have been included in the experiments. In these studies the samples from Oregon and Turkey produced a very high incidence of tumours. All the rats inoculated intrapleurally with Oregon erionite and almost all those inoculated with the Turkish fibre died with a mesothelioma. Inhalation of the Oregon erionite induced a similar effect. No other dusts we have investigated have produced this high incidence of tumours particularly following inhalation. These studies demonstrate that we now have a valuable new fibre for experimental study and a possible hazard to man in regions other then Turkey.}, } @article {pmid2864630, year = {1985}, author = {Chiappino, G}, title = {[Effects of low-level exposure to asbestos in man].}, journal = {La Medicina del lavoro}, volume = {76}, number = {3}, pages = {179-191}, pmid = {2864630}, issn = {0025-7818}, mesh = {Air Pollution ; Alcohol Drinking ; Asbestos/*adverse effects ; Asbestos, Amosite ; Asbestos, Crocidolite ; Asbestosis/*etiology ; Child ; Environmental Exposure ; Female ; Humans ; Laryngeal Neoplasms/etiology ; Lung Neoplasms/etiology ; Male ; Mesothelioma/etiology ; Occupational Diseases/etiology ; Peritoneal Neoplasms/etiology ; Pleural Neoplasms/etiology ; Risk ; Smoking ; }, } @article {pmid4001663, year = {1985}, author = {Vande Weyer, R and De Vuyst, P}, title = {[The pathology of asbestos in Belgium].}, journal = {Revue medicale de Bruxelles}, volume = {6}, number = {4}, pages = {295-297}, pmid = {4001663}, issn = {0035-3639}, mesh = {Asbestosis/complications/*epidemiology ; Belgium ; Humans ; Lung/pathology ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Occupational Diseases/complications/*epidemiology ; }, } @article {pmid2983751, year = {1985}, author = {Alies-Patin, AM and Valleron, AJ}, title = {Mortality of workers in a French asbestos cement factory 1940-82.}, journal = {British journal of industrial medicine}, volume = {42}, number = {4}, pages = {219-225}, pmid = {2983751}, issn = {0007-1072}, mesh = {Adolescent ; Adult ; Aged ; Asbestos/*adverse effects ; Asbestos, Crocidolite ; Asbestos, Serpentine ; Calcium Hydroxide/adverse effects ; *Chemical Industry ; Child ; France ; Humans ; Lung Neoplasms/mortality ; Male ; Mesothelioma/mortality ; Middle Aged ; Neoplasms/*mortality ; Occupational Diseases/*mortality ; Risk ; Time Factors ; }, abstract = {The mortality of a complete cohort of 1506 French asbestos cement workers employed for at least five years is related to the time elapsed since first exposure. The mortality from all causes (analysed by the "man-years method") has been found to be above normal only in those subjects employed for more than 20 years, with more than 35 years of follow up. Standardised mortality ratios for cancers of all sites (ICD 140-209) and pulmonary cancer (ICD 162-163.0) have been assessed in subjects whose first exposure dates go back more than 20 years. Mortalities from cancer of all sites and from pulmonary cancer have been detected in excess in workers employed for more than 20 years and originally hired when aged 25 or under.}, } @article {pmid3967191, year = {1985}, author = {Efremidis, AP and Waxman, JS and Chahinian, AP}, title = {Association of lymphocytic neoplasia and mesothelioma.}, journal = {Cancer}, volume = {55}, number = {5}, pages = {1056-1059}, doi = {10.1002/1097-0142(19850301)55:5<1056::aid-cncr2820550522>3.0.co;2-v}, pmid = {3967191}, issn = {0008-543X}, mesh = {Aged ; Asbestos/*adverse effects ; Humans ; Leukemia, Lymphoid/complications/*etiology ; Lymphoma/complications/*etiology ; Male ; Mesothelioma/complications/*etiology ; Middle Aged ; Neoplasms, Multiple Primary/etiology ; Pleural Neoplasms/complications/*etiology ; }, abstract = {Two lymphocytic neoplasms, chronic lymphocytic leukemia and poorly differentiated lymphoma, were detected in two patients who had nonoccupational exposure to asbestos. Both had a pleural mesothelioma subsequent to their initial presentation with lymphocytic neoplasm. Recent reports have suggested a possible association between asbestos exposure and lymphoproliferative neoplasms. Chronic antigenic stimulation by asbestos could predispose one to the immunoproliferative disorders seen in these patients. The possible significance of this relationship is discussed for future consideration.}, } @article {pmid3891207, year = {1985}, author = {Antman, KH and Corson, JM}, title = {Benign and malignant pleural mesothelioma.}, journal = {Clinics in chest medicine}, volume = {6}, number = {1}, pages = {127-140}, pmid = {3891207}, issn = {0272-5231}, mesh = {Adult ; Antineoplastic Agents/therapeutic use ; Asbestos/adverse effects ; Child, Preschool ; Combined Modality Therapy ; Humans ; *Mesothelioma/diagnosis/epidemiology/etiology/pathology/therapy ; Pleura/pathology/surgery ; Pleural Effusion/therapy ; *Pleural Neoplasms/diagnosis/epidemiology/etiology/pathology/therapy ; Radiotherapy Dosage ; Risk ; }, abstract = {Malignant mesotheliomas have assumed an importance in the medical and lay literature out of proportion to their incidence in the American population, chiefly due to the known association of pleural mesothelioma with asbestos exposure. Data from the Connecticut tumor registry suggest that this tumor is increasing in incidence. Based on exposures between 1940 and approximately 1970, when industrial precautions were first instituted, epidemiologists estimate that the number of new cases of mesothelioma will peak sometime in the 1990s and that mesothelioma will thereafter become less common. These models generally assume that asbestos exposures after 1970 will be insignificant. While industrial levels that are legal today will almost certainly prevent the development of severe asbestosis in most workers, unfortunately a threshold of exposure below which there is no risk of mesothelioma has not been documented. Asbestos continues to be used in floor and ceiling tiles, in automobile brake linings, and in a variety of other products. At the present time, construction workers who maintain or remove asbestos constitute one of a number of groups with continued exposure. The diagnosis of a malignant pleural mesothelioma is not difficult provided that the physicians caring for such a patient consider mesothelioma in the differential diagnosis. Patients present with chest pain or shortness of breath, or both, and the initial chest x-ray film most often reveals a large unilateral pleural effusion. The tumor characteristically remains localized until late in its course, and thus extensive workup at the time of diagnosis is seldom required. Generally, a large piece of tissue obtained via an open biopsy is required for adequate histologic diagnosis. Investigational approaches include taking numerous needle biopsies with samples sent for electron microscopy as well as for immunoperoxidase staining for keratin and CEA. The treatment of this disease remains unsatisfactory. Occasional patients have remained disease-free for periods in excess of 5 years after intensive treatment, however. The conclusion that mesothelioma is untreatable is clearly untenable since palliation and a response rate of 30 per cent to various chemotherapeutic regimens have been reported by a number of investigators. While many authors have advocated supportive care alone because "current treatments have not demonstrated increased survival," we believe patients with mesothelioma should be offered investigational therapy.(ABSTRACT TRUNCATED AT 400 WORDS)}, } @article {pmid3871564, year = {1985}, author = {Armas, RR and Goldsmith, SJ}, title = {Gallium scanning in peritoneal mesothelioma.}, journal = {AJR. American journal of roentgenology}, volume = {144}, number = {3}, pages = {563-565}, doi = {10.2214/ajr.144.3.563}, pmid = {3871564}, issn = {0361-803X}, mesh = {Adult ; Female ; *Gallium Radioisotopes ; Humans ; Male ; Mesothelioma/*diagnostic imaging ; Middle Aged ; Peritoneal Neoplasms/*diagnostic imaging ; Radionuclide Imaging ; }, abstract = {Gallium scans in seven cases of pathologically proven primary peritoneal mesothelioma were reviewed and correlated with clinical, radiologic, and surgical findings. Although five patients gave a history of asbestos exposure, only two showed chest film findings typical of asbestosis. Most had abdominal discomfort, ascites, and abdominal masses. Five of the seven had positive gallium scans; three showed a large single focus of uptake and two showed diffuse abdominal uptake. Although these patterns correspond to the two main gross pathologic types described in peritoneal mesothelioma, there was not complete agreement with clinical, radiographic, and surgical findings, and the focal pattern tended to underestimate the extent of the disease. Although gallium uptake can be seen in a variety of other neoplastic and inflammatory conditions, it may be useful in the diagnosis and follow-up of peritoneal mesothelioma.}, } @article {pmid3156981, year = {1985}, author = {Chase, GR and Kotin, P and Crump, K and Mitchell, RS}, title = {Evaluation for compensation of asbestos-exposed individuals. II. Apportionment of risk for lung cancer and mesothelioma.}, journal = {Journal of occupational medicine. : official publication of the Industrial Medical Association}, volume = {27}, number = {3}, pages = {189-198}, pmid = {3156981}, issn = {0096-1736}, mesh = {Adolescent ; Adult ; Aged ; Asbestos/*adverse effects ; Biometry ; Humans ; Lung Neoplasms/epidemiology/etiology ; Male ; Mesothelioma/epidemiology/etiology ; Middle Aged ; Occupational Diseases/epidemiology/*etiology ; Risk ; Smoking ; Time Factors ; *Workers' Compensation ; }, abstract = {The incidence of lung cancer in the cigarette smoking population occupationally exposed to asbestos is inordinately high. A method for apportioning risk to these two agents has been developed. It utilizes degree of asbestos and smoking exposures; the time interval from onset and, where applicable, termination of both exposures; the time interval to diagnosis of lung cancer; and morphologic, physiologic, and radiological evidence of pulmonary fibrosis.}, } @article {pmid2989120, year = {1985}, author = {Kulagina, TF and Pylev, LN}, title = {[Morphological assessment of pleural tumors induced in rats by Dzhetygara chrysotile asbestos and lizardite].}, journal = {Gigiena truda i professional'nye zabolevaniia}, volume = {}, number = {3}, pages = {27-29}, pmid = {2989120}, issn = {0016-9919}, mesh = {Animals ; Asbestos/*toxicity ; Asbestos, Serpentine ; Dust/adverse effects ; Female ; Kazakhstan ; Male ; Mesothelioma/*etiology/pathology ; Pleural Neoplasms/*etiology/pathology ; Rats ; }, } @article {pmid3984378, year = {1985}, author = {De Kraay, WH}, title = {Malignant mesothelioma.}, journal = {Wisconsin medical journal}, volume = {84}, number = {2}, pages = {32-34}, pmid = {3984378}, issn = {0043-6542}, mesh = {Aged ; Asbestos/*adverse effects ; Female ; Humans ; Lung Neoplasms/*diagnosis ; Male ; Mesothelioma/*diagnosis ; Middle Aged ; Occupational Diseases/*diagnosis ; Pleural Neoplasms/*diagnosis ; }, } @article {pmid3967217, year = {1985}, author = {Lynch, HT and Katz, D and Markvicka, SE}, title = {Familial mesothelioma: review and family study.}, journal = {Cancer genetics and cytogenetics}, volume = {15}, number = {1-2}, pages = {25-35}, doi = {10.1016/0165-4608(85)90128-1}, pmid = {3967217}, issn = {0165-4608}, mesh = {Aged ; Asbestos ; Female ; Humans ; Male ; Mesothelioma/etiology/*genetics/pathology ; Middle Aged ; Occupational Diseases/genetics ; Pedigree ; }, abstract = {To date, with few exceptions, primary attention to the etiology of malignant mesothelioma has been focused on environmental factors. However, several reports of familial aggregations of mesothelioma strongly support the supposition that host factors, in concert with environmental exposure, particularly asbestos, may contribute etiologically to an as yet unknown fraction of occurrences of this disease. However, in evaluation of familial mesothelioma, it is important to consider the possibility of household exposure to asbestos. We report a family in which two brothers with prolonged occupational asbestos exposure manifested malignant pleural mesotheliomas of similar histology.}, } @article {pmid3965116, year = {1985}, author = {Churg, A}, title = {Malignant mesothelioma in British Columbia in 1982.}, journal = {Cancer}, volume = {55}, number = {3}, pages = {672-674}, doi = {10.1002/1097-0142(19850201)55:3<672::aid-cncr2820550333>3.0.co;2-z}, pmid = {3965116}, issn = {0008-543X}, mesh = {Asbestos/analysis ; British Columbia ; Female ; Humans ; Male ; Mesothelioma/analysis/*epidemiology ; Occupations ; Peritoneal Neoplasms/*epidemiology ; Pleural Neoplasms/analysis/*epidemiology ; }, abstract = {All cases newly diagnosed by a pathologist in 1982 in British Columbia as a malignant mesothelioma of the pleura or peritoneum were reviewed. In men there were 17 cases (incidence rate, 17.0/million/year), and in women 2 cases (1.9/million/year). A history of asbestos exposure (largely in shipyards, construction, or insulation work) was obtained for 14 of 15 men, and 0 of 1 woman. Mineralogic analysis of lung on 6 of the men confirmed that the tumor was associated in every instance with exposure to amosite and crocidolite asbestos; some patients also had elevated levels of tremolite asbestos, presumably reflecting exposure to a chrysotile asbestos product. No unusual levels of asbestos were found in the lungs of the one woman studied. These data show that the incidence rate of mesothelioma in British Columbia has increased nearly six times for men compared to the period 1969 to 1975, but has remained roughly unchanged for women. Almost all of the cases in men in this series could be linked to asbestos exposure.}, } @article {pmid2981541, year = {1985}, author = {Brown, DG and Johnson, NF and Wagner, MM}, title = {Multipotential behaviour of cloned rat mesothelioma cells with epithelial phenotype.}, journal = {British journal of cancer}, volume = {51}, number = {2}, pages = {245-252}, pmid = {2981541}, issn = {0007-0920}, mesh = {Animals ; Asbestos ; Asbestos, Crocidolite ; Cell Adhesion ; Cell Line ; Female ; Mesothelioma/etiology/pathology/*ultrastructure ; Microscopy, Electron ; Neoplastic Stem Cells/ultrastructure ; Rats ; Rats, Inbred Strains ; }, abstract = {Reference cultures derived from a transplantable rat mesothelioma were obtained by cloning cells three times in soft agar. Each line, designated "CARM-Lines", was selected on the basis of their epithelial or fibroblastic phenotype, and their uniform morphology. Three epithelial lines were used for more detailed in vitro studies comparing morphological and biological criteria at early and late passages. All three lines exhibited both epithelial and fibroblastic elements after 10-14 passages in vitro, demonstrating that the dimorphic histology of these tumours could be derived from a single aberrant cell. Morphology and growth characteristics of these cells were density-dependent. Anchorage dependent and independent clonogenic assays did not correlate. Anchorage dependent colony formation was the only parameter which differed markedly from the original parent line in the assays described. In vivo evidence of chondrogenesis and attempted ossification support the concept of a multipotential cell contributing to the diverse primary tumour morphology by cellular modulation or differentiation.}, } @article {pmid4081475, year = {1985}, author = {Molina, C and Perdrizet, S and Cheminat, JC and Maillet, J and Bedu, M and Caillaud, D}, title = {[Lessons from a long-term survey on the effects of massive occupational exposure to asbestos. The AMISOL affair 10 years later].}, journal = {Revue de pneumologie clinique}, volume = {41}, number = {4}, pages = {225-232}, pmid = {4081475}, issn = {0761-8417}, mesh = {Asbestosis/diagnostic imaging/*epidemiology/physiopathology ; Follow-Up Studies ; France ; Humans ; Lung/diagnostic imaging ; Radiography ; Risk ; Textile Industry ; Time Factors ; }, abstract = {For the past 10 years the authors have followed up a cohort of workers who had been massively exposed to dust in an asbestos textile factory which closed down in 1974. They report on the difficulties of all kinds they encountered during this epidemiological survey. The most original result is that they were able to establish that the radiological and functional manifestations of asbestosis pursue their course after the subjects have ceased to be exposed. Another important point is the early development of lesions in peripheral bronchioles, detected by volume-flow loops. The authors insist on the psycho-social problems at the site of work or in daily life which arise from the use of asbestos or of fibres with similar properties. Social protection, at present well organized, should suppress the risk of asbestosis in Western countries. However, a number of problems remain to be solved, notably those concerning the long-term risk of pleural mesothelioma, the mode of action of the fibers and the immune reactions they induce, and the economic and social consequences of a hypothetical ban on asbestos--a material very difficult to replace. This study embodies, in miniature, all the problems of society associated with asbestos during this second half of the XX th century.}, } @article {pmid4062141, year = {1985}, author = {Douvier, JJ and Vergeret, J and Taytard, A and Brottier, E and Domblides, P and Dubos, F and Freour, P}, title = {[Bromocriptine in Parkinson's disease: pleuropulmonary toxicity].}, journal = {Annales de medecine interne}, volume = {136}, number = {5}, pages = {416-418}, pmid = {4062141}, issn = {0003-410X}, mesh = {Bromocriptine/*adverse effects ; Humans ; Male ; Middle Aged ; Parkinson Disease/*drug therapy ; Pleural Diseases/*chemically induced/diagnosis ; Pulmonary Fibrosis/*chemically induced/diagnosis ; }, abstract = {The authors report a case of pleuro-pulmonary fibrosis after 9 months of high dose bromocriptine therapy for the treatment of Parkinson's disease. When the drug was stopped there was a significant improvement of the clinical state with complete regression of chest pain and dyspnea of effort. The major inflammatory biological syndrome disappeared completely. Chest X-rays showed partial improvement with signs of pleural pneumonitis. The results of ventilatory and respiratory function tests stabilised. After one year follow-up, the causal relationship of this iatrogenic pathology has therefore been established. The initial diagnostic problems are stressed, particularly with respect to malignant disease (mesothelioma) when there has been exposure to asbestos, as in our case. The early stages must be carefully looked for so as to prevent fibrosing complications. The presence of immune complexes in our case could indicate immuno-allergic mechanism.}, } @article {pmid4012013, year = {1985}, author = {Dongay, G and Levade, M and Lauque, D and Carles, P and Bollinelli, R}, title = {[Computerized tomography of pleuropulmonary pathology due to asbestos].}, journal = {Revue des maladies respiratoires}, volume = {2}, number = {1}, pages = {31-36}, pmid = {4012013}, issn = {0761-8425}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Asbestosis/*diagnostic imaging ; Female ; Humans ; Male ; Mesothelioma/*diagnostic imaging/etiology ; Middle Aged ; Pleural Neoplasms/*diagnostic imaging/etiology ; *Tomography, X-Ray Computed ; }, abstract = {28 patients presenting with proven pleuro-pulmonary pathology due to asbestos underwent conventional radiography and also computed tomography (TDM). It is evident that TDM was more sensitive in detecting the presence of pleural plaques which were either hidden or invisible on standard radiographs. False parietal images were often eliminated. With a mesothelioma it can guide the biopsy approach and by visualising contra-lateral plaques that the origin is asbestos. It should enable irregular plaques to be monitored more easily.}, } @article {pmid4002674, year = {1985}, author = {Topov, Ia and Kolev, K}, title = {[Ultrastructure of asbestos-induced mesotheliomas].}, journal = {Voprosy onkologii}, volume = {31}, number = {4}, pages = {75-78}, pmid = {4002674}, issn = {0507-3758}, mesh = {Animals ; Asbestos/*toxicity ; Female ; Mesothelioma/etiology/*ultrastructure ; Microscopy, Electron ; Peritoneal Neoplasms/etiology/*ultrastructure ; Pleural Neoplasms/etiology/*ultrastructure ; Rats ; Rats, Inbred Strains ; }, abstract = {Experimental mesotheliomas induced in albino rats by treatment with isometric crocidolite asbestos were studied by light and electron microscopy. The cellular structure of different types of neoplasms was examined. The ultrastructural investigation was carried out using both freshly-resected materials and those recovered from paraffin blocks. The characteristic features of nuclei and cytoplasm are described with special attention being given to cytoplasmic organelles. On the basis of morphological light and electron microscopic study the authors discuss the histogenesis of different types of mesotheliomas. An attempt is being made to establish the origin of fibromatous mesotheliomas and to improve the available classifications.}, } @article {pmid3994811, year = {1985}, author = {Davis, DL and Mandula, B}, title = {Airborne asbestos and public health.}, journal = {Annual review of public health}, volume = {6}, number = {}, pages = {195-221}, doi = {10.1146/annurev.pu.06.050185.001211}, pmid = {3994811}, issn = {0163-7525}, mesh = {Air Pollutants/*adverse effects ; Asbestos/*adverse effects ; Asbestosis/*etiology/mortality/prevention & control ; Dose-Response Relationship, Drug ; Dust/*adverse effects ; Gastrointestinal Neoplasms/etiology ; Humans ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Risk ; }, } @article {pmid3993648, year = {1985}, author = {Zoloth, S and Michaels, D}, title = {Asbestos disease in sheet metal workers: the results of a proportional mortality analysis.}, journal = {American journal of industrial medicine}, volume = {7}, number = {4}, pages = {315-321}, doi = {10.1002/ajim.4700070407}, pmid = {3993648}, issn = {0271-3586}, mesh = {Aged ; Asbestos/*adverse effects ; Colonic Neoplasms/etiology/*mortality ; Humans ; Lung Neoplasms/etiology/*mortality ; Male ; Mesothelioma/etiology/mortality ; *Metallurgy ; Occupational Diseases/etiology/*mortality ; Rectal Neoplasms/etiology/*mortality ; Regression Analysis ; }, abstract = {The results of a proportional mortality analysis of a cohort of sheet metal workers who have only intermittent exposure to asbestos demonstrates a significant excess of cancer at the three sites most frequently associated with asbestos: lung, colon and rectum, and the mesothelium. No excess nonmalignant respiratory disease was detected. These data strongly suggest that significant asbestos-related disease is present in populations with secondary exposure to asbestos and emphasize the importance of considering possible asbestos-related disease when treating patients with a history of employment in the construction industry.}, } @article {pmid3975384, year = {1985}, author = {Otto, H and Bohlig, H}, title = {[Morphology and roentgenology of asbestosis].}, journal = {Der Radiologe}, volume = {25}, number = {1}, pages = {9-21}, pmid = {3975384}, issn = {0033-832X}, mesh = {Asbestosis/*diagnostic imaging/pathology ; Carcinoma, Bronchogenic/diagnostic imaging ; Humans ; Lung/pathology ; Lung Neoplasms/diagnostic imaging ; Mesothelioma/diagnostic imaging ; Pleural Diseases/diagnostic imaging ; Radiography ; Risk ; Smoking ; }, abstract = {The different sequelae of lung and pleura resulting from the inhalation of asbestos dust are discussed in detail, taking into consideration the improvements in dust-control measures. The use of Lung Dust Separation and Investigation and Radiological Classification of Pneumoconioses (ILO 1980) with regard to diagnostics is critically reviewed. Certain problems of compensation for asbestos-induced neoplasms are pointed out with special reference to the regulations of the Federal Republic of Germany.}, } @article {pmid3973571, year = {1985}, author = {Morse, RH}, title = {A difficult chest pain.}, journal = {The Journal of the Louisiana State Medical Society : official organ of the Louisiana State Medical Society}, volume = {137}, number = {1}, pages = {17-8, 20}, pmid = {3973571}, issn = {0024-6921}, mesh = {Asbestos/adverse effects ; Humans ; Male ; Mesothelioma/*diagnosis ; Middle Aged ; *Pain ; Thoracic Neoplasms/*diagnosis ; *Thorax ; }, } @article {pmid3966966, year = {1985}, author = {Gardner, MJ and Jones, RD and Pippard, EC and Saitoh, N}, title = {Mesothelioma of the peritoneum during 1967-82 in England and Wales.}, journal = {British journal of cancer}, volume = {51}, number = {1}, pages = {121-126}, pmid = {3966966}, issn = {0007-0920}, mesh = {Adult ; Age Factors ; Aged ; Asbestos/adverse effects ; England ; Female ; Humans ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Diseases/etiology ; Peritoneal Neoplasms/*epidemiology/etiology ; Sex Factors ; Wales ; }, abstract = {The time-trend and geographical distribution of mesothelioma of the peritoneum during the years 1967-82 in England and Wales have been studied from the Mesothelioma Register held by the Medical Division of the Health and Safety Executive. Over the 16-year period the annual number of cases registered rose from about 15-20 to about 30-50. Although the number occurring in men was double that in women, the trend was similar for both sexes. There is likely to be some further increase before any improvement due to the recent diminished usage of asbestos is seen. Local Authority areas with raised rates have been identified, and the geographical pattern is similar to that of the distribution of the asbestos-using industry in the past. In both sexes there are high registration rates on the east side of London but, in contrast to mesothelioma of the pleura, a concentration of cases among men in the major ports where shipbuilding and ship repairing were carried out is not so apparent.}, } @article {pmid3965021, year = {1985}, author = {Finkelstein, M}, title = {On the relative toxicity of asbestos fibres.}, journal = {British journal of industrial medicine}, volume = {42}, number = {1}, pages = {69-70}, pmid = {3965021}, issn = {0007-1072}, mesh = {Asbestos/*adverse effects ; Humans ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; }, } @article {pmid3965014, year = {1985}, author = {Newhouse, ML and Berry, G and Wagner, JC}, title = {Mortality of factory workers in east London 1933-80.}, journal = {British journal of industrial medicine}, volume = {42}, number = {1}, pages = {4-11}, pmid = {3965014}, issn = {0007-1072}, mesh = {Adult ; Age Factors ; Asbestos/*adverse effects ; Asbestosis/mortality ; Female ; Follow-Up Studies ; Gastrointestinal Neoplasms/etiology/mortality ; Humans ; London ; Lung Neoplasms/etiology/mortality/pathology ; Male ; Mesothelioma/etiology/mortality ; Middle Aged ; Neoplasms/etiology/mortality ; Occupational Diseases/etiology/*mortality ; Sex Factors ; }, abstract = {The mortality of 3000 male factory workers, 1400 laggers, and 700 women factory workers in east London has been studied. The men were first employed between 1933 and 1964, the women between 1936 and 1942. Textiles were produced until the late 1950s as well as other asbestos products. Laggers were employed on contract in increasing numbers in later years. Crocidolite asbestos was used until the late 1950s as well as asmosite and chrysotile. Exposure of workers was graded according to the job into two categories, low/moderate and severe, and subdivided by duration of employment up to two years or longer. Mesothelial tumours accounted for 7.5% of the total mortality in men, and 9% in women with their longer follow up period. Lung cancer accounted for 20% of deaths in men and 14% in women. Both mesothelial tumours and lung cancer showed a dose response relationship. Histopathological examination of a series of predominantly postmortem specimens showed 22% of adenocarcinomas of lung among men and 21% in women. There was an excess of gastrointestinal tumours but no dose response relationship could be shown. Among severely exposed male factory workers there was an excess of deaths from cancer of the larynx and among severely exposed women of carcinoma of the breast and ovary. Twenty four deaths (2%) were due to asbestosis. There is an indication that the incidence of mesothelial tumours is declining but a further period of observation is required for confirmation.}, } @article {pmid3965010, year = {1985}, author = {Berry, G and Newhouse, ML and Antonis, P}, title = {Combined effect of asbestos and smoking on mortality from lung cancer and mesothelioma in factory workers.}, journal = {British journal of industrial medicine}, volume = {42}, number = {1}, pages = {12-18}, pmid = {3965010}, issn = {0007-1072}, mesh = {Adolescent ; Adult ; Aged ; Asbestos/*adverse effects ; Female ; Follow-Up Studies ; Humans ; London ; Lung Neoplasms/etiology/*mortality ; Male ; Mesothelioma/etiology/*mortality ; Middle Aged ; Occupational Diseases/etiology/*mortality ; Prospective Studies ; Retrospective Studies ; *Smoking ; }, abstract = {The mortality of over 1250 male and 420 female asbestos factory workers was observed over the period 1971-80. Smoking habits were obtained from the subjects in 1971 before the start of the follow up period. Mortality due to lung cancer and to mesothelioma was related to smoking habits. After allowing for the effect of smoking on lung cancer the relative risk due to asbestos was highest for those who had never smoked, lowest for current smokers, and intermediate for ex-smokers; the trend was statistically significant (p less than 0.05). There was no significant association between smoking and deaths due to mesothelioma. Data from several studies are reviewed, and although overall non-smokers have a relative risk of lung cancer due to asbestos that is 1.8 times that of smokers, there is some uncertainty on the accuracy of this figure because of possible biases and sampling variation. Overall the evidence is that mesothelioma risk is independent of smoking.}, } @article {pmid3896651, year = {1985}, author = {Raptopoulos, V}, title = {Peritoneal mesothelioma.}, journal = {Critical reviews in diagnostic imaging}, volume = {24}, number = {4}, pages = {293-328}, pmid = {3896651}, issn = {1040-8371}, mesh = {Adult ; Asbestos/adverse effects ; Diagnosis, Differential ; Female ; Gallium Radioisotopes ; Humans ; Male ; Mesothelioma/*diagnosis/etiology/therapy ; Middle Aged ; Neoplasm Metastasis ; Peritoneal Neoplasms/*diagnosis/etiology/therapy ; Physical Examination ; Pleural Neoplasms/diagnosis ; Tomography, X-Ray Computed ; Ultrasonography ; }, abstract = {The definitive diagnosis of peritoneal mesothelioma and its differentiation from metastatic peritoneal carcinomatosis may be difficult because of the clinical, macroscopic, and microscopic variability of the tumor. To this purpose, a combination of criteria, including the clinical picture, the gross pathologic findings, the exclusion of other primary neoplasms, and the microscopic findings, must be taken into consideration. Conventionally, these criteria may be established only after surgical exploration and extensive sampling. Our experience with patients with peritoneal mesothelioma and metastatic peritoneal carcinomatosis, as well as a review of the recent imaging literature, shows excellent correlation between computed tomography or ultrasound and the operative or autopsy findings. These imaging modalities showed soft-tissue masses or nodules; thickened omentum ("omental cake"), peritoneum, mesentery, and bowel wall; pleural plaques; and usually disproportionally small, if any, ascites. The latter two observations may be useful in differentiating mesothelioma from carcinomatosis macroscopically. Furthermore, fine-needle aspiration biopsy, after performing wide sampling of the tumors in different locations under ultrasonic or computed tomographic guidance, produced diagnostic cytologic specimens. Thus, the need for exploratory surgery may be alleviated, and the diagnosis of peritoneal mesothelioma may be made prospectively and relatively noninvasively with the use of computed tomography or ultrasound and fine-needle aspiration biopsy. Since epidemiologic studies predict increasing incidence of this neoplasm, especially among asbestos workers, it is suggested that these techniques be seriously considered as screening methods for high-risk populations.}, } @article {pmid3891228, year = {1985}, author = {Vallyathan, V and Green, FH}, title = {The role of analytical techniques in the diagnosis of asbestos-associated disease.}, journal = {Critical reviews in clinical laboratory sciences}, volume = {22}, number = {1}, pages = {1-42}, doi = {10.1080/10408368509176814}, pmid = {3891228}, issn = {1040-8363}, mesh = {Asbestos/*adverse effects/analysis ; Asbestosis/*diagnosis/pathology ; Carcinoma, Bronchogenic/pathology ; Environmental Exposure ; Humans ; Lung Diseases/pathology ; Lung Neoplasms/pathology ; Mesothelioma/pathology ; Microscopy, Electron ; Microscopy, Electron, Scanning ; Spectrometry, X-Ray Emission ; }, abstract = {There is increasing concern over the adverse health effects resulting from asbestos exposure. The mineralogy of asbestos and the pathology of asbestos-associated diseases is briefly reviewed. Techniques for tissue sampling, histopathological diagnostic criteria and the role of light microscopy (LM), scanning electron microscopy (SEM), transmission electron microscopy (TEM), selected area electron diffraction (SAED), and X-ray diffractometry (XRD)--in the identification and quantitation of asbestos bodies and fibers in the lung tissue samples--are discussed. The value of a systematic quantitative approach is emphasized in order to differentiate the dose relationships and disease patterns.}, } @article {pmid3882332, year = {1985}, author = {Lee, KP}, title = {Lung response to particulates with emphasis on asbestos and other fibrous dusts.}, journal = {Critical reviews in toxicology}, volume = {14}, number = {1}, pages = {33-86}, doi = {10.3109/10408448509023764}, pmid = {3882332}, issn = {1040-8444}, mesh = {Animals ; Asbestos/*adverse effects ; Asbestosis/metabolism/pathology ; Dust/*adverse effects ; Glass ; Humans ; Intubation, Intratracheal ; Lung/metabolism/*pathology ; Lung Neoplasms/etiology/pathology ; Mesothelioma/etiology/pathology ; Particle Size ; Pleura/drug effects ; Protein Biosynthesis ; }, abstract = {Many theories have been proposed to explain asbestosis and asbestos-related pulmonary disease. However, none of the theories give a completely plausible explanation for the pathogenesis. Recently, attention has been drawn to a theory that the fibrogenicity or carcinogenicity of fibrous dust particles is related to fiber diameter and length rather than to chemical properties. This theory may help partially elucidate the disease process but is still far from solving the enigma of pulmonary fibrosis or carcinogenesis. The theory cannot explain the absence of these pathological effects among fiberglass workers or experimental animals exposed by inhalation (even though mesotheliomas are induced by intrapleural implantation and fiber dimension-related fibrogenicity is demonstrated by intratracheal injection). Little information regarding the pulmonary response to manmade fibrous particles is available in animals following inhalation exposure. Attempts should be made to confirm the absence of adverse effects using animal inhalation experiments even though to this point there is no conclusive evidence that either lung cancer or pulmonary diseases can be produced among employees in manmade fiber industries. A new research trend seems concentrated on testing the durability of asbestos or manmade fibers. This is based on the concept that biological effects of fibrous particles are the result of relative durability and that particles which can be fragmented or shortened may be less pathogenic. In the last two decades, considerable understanding about pulmonary fibrosis and carcinogenesis of asbestos has been achieved by clinical and animal experiments. In vitro tests including cytotoxicity, hemolysis, immunology, and enzyme biochemistry have provided important information on the interrelationships among these various biological effects of asbestos.}, } @article {pmid3855488, year = {1985}, author = {Malker, HS and McLaughlin, JK and Malker, BK and Stone, BJ and Weiner, JA and Erickson, JL and Blot, WJ}, title = {Occupational risks for pleural mesothelioma in Sweden, 1961-79.}, journal = {Journal of the National Cancer Institute}, volume = {74}, number = {1}, pages = {61-66}, pmid = {3855488}, issn = {0027-8874}, mesh = {Female ; Humans ; Male ; Mesothelioma/*epidemiology ; *Occupations ; Pleural Neoplasms/*epidemiology ; Risk ; Sweden ; }, abstract = {From national population-based registries linking cancer incidence from 1961 to 1979 with 1960 census data on industry and occupation for all employed individuals in Sweden, a systematic assessment was made of pleural mesothelioma occurrence according to occupational and industrial classifications. There were 318 cases of pleural mesothelioma recorded during the 19-year follow-up period among males employed in 1960, with significant variation by industrial and occupational categorizations. The observed number of pleural mesotheliomas for men employed in the sugar refining, cellulose, wood and pulp, shipbuilding, and railroad equipment manufacturing industries was more than three times the number expected. Occupations with at least twofold excess of mesotheliomas included the craftsman categories of plumbers, mechanics and repairmen, electricians, painters, tire makers, and stationary equipment operators. Our findings are consistent with available data relating mesothelioma to occupational asbestos exposure in other countries, although unexpected associations were found that deserve further epidemiologic study.}, } @article {pmid3832198, year = {1985}, author = {de Vuyst, P and Dumortier, P and Vande Weyer, R and Walravens, C and Rocmans, P and Ketelbant, P and Yernault, JC}, title = {[The diagnostic value of asbestos bodies in mesotheliomas].}, journal = {Revue des maladies respiratoires}, volume = {2}, number = {5}, pages = {295-299}, pmid = {3832198}, issn = {0761-8425}, mesh = {Adult ; Aged ; Asbestos/adverse effects/*analysis ; Asbestosis/diagnosis ; Bronchi/metabolism ; Exudates and Transudates/analysis ; Humans ; Male ; Mesothelioma/*etiology ; Middle Aged ; Peritoneal Neoplasms/etiology ; Pleural Neoplasms/*etiology ; Pulmonary Alveoli/metabolism ; Therapeutic Irrigation ; }, abstract = {The exposure of asbestos was studied in 31 cases of mesothelioma from case histories and by microscopic mineralogical analysis of the broncho-alveolar lavage fluid (BAL) (31 cases) and of pulmonary tissue (5 cases). When definite exposure had occurred the lavage contained asbestos bodies in every case, except one patient with severe airflow obstruction. The most positive lavages, probably reflecting exposure to industrial amphiboles, were found in patients presenting with radiological evidence of asbestosis. Two patients had positive lavages 50 years after exposure had ceased. The lavage confirmed exposure in 6 out of 11 suspected cases and revealed contamination by asbestos in a further 4 cases, in a group of 6 not known to have been exposed. In 19.3% of cases there was a low concentration of asbestos bodies (less than 1AB/ml of BAL), comparable to what is found in 16.2% of controls from an urban population. An analysis of lung tissue confirmed massive exposure (greater than 20 000 AB/g) in two cases and in particular revealed a significant dust load (greater than 250 AB/g) in patients presenting with a weak positive BAL. Thus it seems that all the positive results should be taken into account. Of the 31 cases, 8 had a BAL without asbestos bodies. These were either mesotheliomas not linked to the inhalation of asbestos, or were the result of false negatives on account of artefacts related either to the BAL technique itself or linked to the technique of mineral analysis. Indeed the microscopic counts of asbestos bodies probably underestimate certain exposures, notably environmental exposure to chrysotile.}, } @article {pmid3000174, year = {1985}, author = {Hilt, B and Langård, S and Andersen, A and Rosenberg, J}, title = {Asbestos exposure, smoking habits, and cancer incidence among production and maintenance workers in an electrochemical plant.}, journal = {American journal of industrial medicine}, volume = {8}, number = {6}, pages = {565-577}, doi = {10.1002/ajim.4700080608}, pmid = {3000174}, issn = {0271-3586}, mesh = {Asbestos/*adverse effects ; Dose-Response Relationship, Drug ; Environmental Exposure ; Humans ; Lung Neoplasms/*etiology ; Male ; Nitrates ; Nitric Acid ; Occupational Diseases/*etiology ; Smoking ; Time Factors ; }, abstract = {The incidence of cancer was studied in a cohort of 287 men who were exposed to asbestos at a nitric acid production plant from 1928 onwards. During the observation period from 1953 through 1980 all cancer cases among the cohort members were identified in The Cancer Registry. For the whole cohort 42 cases of cancer were observed versus 30.6 expected. The figures for cancer of the lungs and pleura combined were 17 observed versus 3.7 expected. The corresponding figures for a heavily exposed subcohort were 11 observed and 1.2 expected. In that group there was also an increased incidence of colon cancer with 3 cases observed against 0.8 cases expected. Within the whole cohort four cases of pleural and one case of peritoneal malignant mesothelioma were found. There was also an increased incidence of malignant melanoma of the skin with 3 cases observed against 0.6 expected. For cancer cases that were registered as of unknown origin there were 7 cases observed and 1.4 expected. There was no increased rate ratio for cancer at any site before 20 years after the first asbestos exposure. The smoking habits of all cohort members were recorded and the relative rates for lung cancer were calculated in relation to smoking habits. In common with previous studies the results indicate a multiplicative model for the interaction between asbestos exposure and smoking in regard to lung cancer risk.}, } @article {pmid2932634, year = {1985}, author = {Craighead, JE and Juliano, EB}, title = {Asbestos-associated disease: can the issues be resolved in the courtroom?.}, journal = {Monographs in pathology}, volume = {}, number = {26}, pages = {211-221}, pmid = {2932634}, issn = {0077-0922}, mesh = {*Asbestosis ; Carcinoma, Bronchogenic/chemically induced ; Humans ; *Jurisprudence ; Lung Neoplasms/*chemically induced ; Mesothelioma/chemically induced ; Time Factors ; Workers' Compensation ; }, } @article {pmid6512935, year = {1984}, author = {Craighead, JE}, title = {Asbestos. An environmental reality.}, journal = {JAMA}, volume = {252}, number = {23}, pages = {3292-3293}, doi = {10.1001/jama.252.23.3292}, pmid = {6512935}, issn = {0098-7484}, mesh = {Asbestos/*adverse effects/analysis ; Humans ; Lung/analysis ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; United States ; Urban Health ; }, } @article {pmid6100140, year = {1984}, author = {Hillerdal, G}, title = {Pleural changes and exposure to fibrous minerals.}, journal = {Scandinavian journal of work, environment & health}, volume = {10}, number = {6 Spec No}, pages = {473-479}, doi = {10.5271/sjweh.2320}, pmid = {6100140}, issn = {0355-3140}, mesh = {Aluminum Silicates/toxicity ; Asbestos/toxicity ; Asbestos, Crocidolite ; Asbestosis/diagnostic imaging/epidemiology ; Finland ; Humans ; Mesothelioma/diagnostic imaging/epidemiology ; Pleural Diseases/diagnostic imaging/epidemiology ; Pleural Neoplasms/diagnostic imaging/epidemiology ; Pneumoconiosis/diagnostic imaging/*epidemiology ; Radiography ; Risk ; Sweden ; Turkey ; Zeolites ; }, abstract = {The pleura is a main target for various reactions related to asbestos exposure. However there are great radiological and clinical differences between the various reactions, and there is also increasing evidence that they have different prognoses. The main reactions are pleural plaques on the one hand and acute pleurisy and diffuse pleural fibrosis on the other. In a population with a low mesothelioma risk, the anthophyllite-exposed population of Northern Karelia in Finland, there are very few reactions of the second type, while plaques are very common. In Turkey, where the exposure is to erionite, the mesothelioma level is extremely high, and reactions of type two are very common in the exposed population. Thus it seems that careful discrimination of the various pleural changes can have prognostic value. There are also indications that plaques do not have any relation to a disturbed immunologic system, while pleurisy and diffuse pleurisy have.}, } @article {pmid6095707, year = {1984}, author = {Churg, A and Wiggs, B and Depaoli, L and Kampe, B and Stevens, B}, title = {Lung asbestos content in chrysotile workers with mesothelioma.}, journal = {The American review of respiratory disease}, volume = {130}, number = {6}, pages = {1042-1045}, doi = {10.1164/arrd.1984.130.6.1042}, pmid = {6095707}, issn = {0003-0805}, mesh = {Aged ; Asbestos/*adverse effects/*metabolism ; *Asbestos, Amphibole ; Asbestos, Serpentine ; Humans ; Lung/*metabolism ; Lung Neoplasms/chemically induced/*metabolism ; Male ; Mesothelioma/chemically induced/*metabolism ; Middle Aged ; Minerals/metabolism ; Occupational Diseases/chemically induced/*metabolism ; }, abstract = {The role of chrysotile asbestos in the genesis of mesotheliomas in humans is disputed. We analyzed the asbestos content of the lung in 6 long-term chrysotile miners and millers who had pleural mesotheliomas. In five patients, only chrysotile ore components (chrysotile and tremolite/actinolite/anthophyllite types of amphibole asbestos) were found, while the sixth patient presented both chrysotile ore components and amosite, a type of asbestos that is not derived from the mining process. The mean number of fibers/g dry lung for the 5 patients with mesothelioma containing only chrysotile ore components was higher (chrysotile 64 X 10(6) and tremolite group 540 X 10(6] than in a group of long-term chrysotile miner control subjects who had no asbestos-related disease (chrysotile 23 X 10(6), tremolite group 58 X 10(6], but some patients with mesothelioma had fiber burdens near the mean of the control range. Fiber sizes and aspect ratios in the mesothelioma group were approximately the same as those in the control subjects, and analysis of fiber distribution failed to show any preferential localization in the periphery of the lung. However, the concentration ratio of tremolite in the lungs of the mesothelioma cases compared to the control cases was 9.3, while the ratio of chrysotile was only 2.8. Our findings provide strong evidence that chrysotile mine dust (chrysotile and amphibole components) can produce mesotheliomas in humans; the greater relative amounts of tremolite group amphiboles present in the patients with mesothelioma raise the possibility that these fibers may be important in the pathogenesis of the tumors.}, } @article {pmid6492343, year = {1984}, author = {}, title = {A physician's guide to asbestos-related diseases. Council on Scientific Affairs.}, journal = {JAMA}, volume = {252}, number = {18}, pages = {2593-2597}, pmid = {6492343}, issn = {0098-7484}, mesh = {Asbestos/*adverse effects ; Asbestosis/*diagnosis/etiology/pathology ; Biopsy ; Carcinoma, Bronchogenic/etiology ; Diagnosis, Differential ; Dose-Response Relationship, Drug ; Environmental Exposure ; Humans ; Lung Neoplasms/diagnosis/etiology ; Mesothelioma/diagnosis/etiology ; Pleura/drug effects ; Pulmonary Fibrosis/diagnosis ; Smoking ; Time Factors ; }, } @article {pmid6437470, year = {1984}, author = {Davies, D}, title = {Are all mesotheliomas due to asbestos?.}, journal = {British medical journal (Clinical research ed.)}, volume = {289}, number = {6453}, pages = {1164-1165}, pmid = {6437470}, issn = {0267-0623}, mesh = {Adult ; Asbestos/*adverse effects ; Child ; Humans ; Mesothelioma/*etiology ; Pleural Neoplasms/*etiology ; Time Factors ; }, } @article {pmid6543973, year = {1984}, author = {Gavelli, G and Zompatori, M and Bernasconi, A and Galleri, C and Canini, R}, title = {[Radiologic diagnosis in malignant pleural mesothelioma].}, journal = {La Radiologia medica}, volume = {70}, number = {11}, pages = {830-836}, pmid = {6543973}, issn = {0033-8362}, mesh = {Asbestosis/complications ; Biopsy ; Diagnosis, Differential ; Female ; Humans ; Lymphatic Metastasis ; Male ; Mesothelioma/*diagnostic imaging/etiology/pathology ; Middle Aged ; Pleural Neoplasms/*diagnostic imaging/etiology/pathology ; Tomography, X-Ray Computed ; }, abstract = {The authors summarize clinical findings and radiological aspects of pleural malignant mesothelioma. This tumor, previously uncommon, is now observed with increasing frequency in developed countries (pathogenetic relationship with asbestos fibers inhalation is proved). Common and uncommon findings are described and 8 new cases are presented. Differential diagnosis between malignant mesothelioma and other primary or secondary pleural tumors is difficult and always requires a confirmation by multiple biopsies and/or thoracotomy. The usefulness of CT study in the accurate staging of mesothelioma is particularly emphasized. In this field CT may completely replace the conventional tomography.}, } @article {pmid6498717, year = {1984}, author = {Morrison, HI and Band, PR and Gallagher, R and Spinelli, J and Wigle, DT}, title = {Recent trends in incidence rates of pleural mesothelioma in British Columbia.}, journal = {Canadian Medical Association journal}, volume = {131}, number = {9}, pages = {1069-1071}, pmid = {6498717}, issn = {0008-4409}, mesh = {Adult ; Age Factors ; Aged ; British Columbia ; Female ; Humans ; Male ; Mesothelioma/*epidemiology/mortality ; Middle Aged ; Occupational Diseases/epidemiology ; Pleural Neoplasms/*epidemiology/mortality ; Sex Factors ; Time Factors ; }, abstract = {A total of 64 cases of pleural mesothelioma were reported in British Columbia between 1973 and 1980, 54 in males and 10 in females. There was a significant (p less than 0.05) increase in the incidence among males. The overall incidence rates were 4.9 and 0.9 per million person-years for males and females respectively. The age distribution of the cases was roughly exponential up to age 70 years. Almost all of the cases were clustered in Cowichan Valley, Capital and Greater Vancouver counties, where there was a high level of shipbuilding activity 30 to 40 years ago. The increased incidence in males may be related to this activity, which involved exposure to asbestos.}, } @article {pmid6498114, year = {1984}, author = {Wright, WE and Sherwin, RP}, title = {Histological types of malignant mesothelioma and asbestos exposure.}, journal = {British journal of industrial medicine}, volume = {41}, number = {4}, pages = {514-517}, pmid = {6498114}, issn = {0007-1072}, support = {P0-1 CA17054/CA/NCI NIH HHS/United States ; }, mesh = {Asbestos/*adverse effects ; Female ; Humans ; Male ; Mesothelioma/*etiology/pathology ; Occupational Diseases/*etiology/pathology ; Peritoneal Neoplasms/*etiology/pathology ; Pleural Neoplasms/*etiology/pathology ; }, abstract = {The Los Angeles County Cancer Surveillance Program abstracts hospital pathology records on almost all cases of cancer occurring in the county. Those cases of pleural and peritoneal mesothelioma that occurred between 1972 and 1978 were identified. Occupational histories were obtained from interviews, and the histopathology of the tumours was reviewed by a member of a mesothelioma reference panel who was unaware of the exposure histories. The relation of asbestos exposure to the three histological types of mesothelioma (epithelial, mesenchymal, and mixed) was studied among the 29 cases for whom occupational histories were available and who were also considered to have histopathology consistent with mesothelioma. The proportion of cases exposed to asbestos was high for both the epithelial (11/17, 65%) and mixed histological types (6/11, 55%). The single case of mesothelioma classified as a mesenchymal type was also exposed to asbestos. Cases who had worked in shipyards were represented in each of the three groups. In cases who had worked in asbestos production and manufacture an exclusively epithelial type of tumour was observed. In cases who had worked as insulators or in heating trades the histological type was predominantly (3/4) mixed. These data do not support the hypothesis that any specific histological type of mesothelioma is especially related to asbestos exposure.}, } @article {pmid6390772, year = {1984}, author = {Davis, JM}, title = {The pathology of asbestos related disease.}, journal = {Thorax}, volume = {39}, number = {11}, pages = {801-808}, pmid = {6390772}, issn = {0040-6376}, mesh = {Asbestos/*adverse effects/analysis ; Asbestosis/diagnosis/etiology/*pathology ; Body Burden ; Environmental Exposure ; Humans ; Lung/analysis/*pathology ; Mesothelioma/diagnosis/pathology ; Microscopy, Electron ; Microscopy, Phase-Contrast ; Pleural Neoplasms/diagnosis ; }, } @article {pmid6093850, year = {1984}, author = {Edwards, RE and Wagner, MM and Moncrieff, CB}, title = {Cell population and histochemistry of asbestos related lesions of rat pleural cavity after injection of various inorganic dusts.}, journal = {British journal of industrial medicine}, volume = {41}, number = {4}, pages = {506-513}, pmid = {6093850}, issn = {0007-1072}, mesh = {Animals ; Asbestos/*toxicity ; Cell Count ; Female ; Granuloma/enzymology/etiology/*pathology ; Male ; Mesothelioma/etiology/*pathology ; Pleura/drug effects/*pathology ; Pleural Diseases/enzymology/etiology/*pathology ; Pleural Neoplasms/pathology ; Rats ; Rats, Inbred Strains ; Silicon Dioxide/toxicity ; }, abstract = {Rats injected intrapleurally with either crocidolite or chrysotile asbestos or silica or saline, were killed at intervals up to 2 years of age. The pleural cavities were washed out immediately after death and the washing used for enumerating cells. In addition tissue from granulomas and mesotheliomas was sectioned and stained for lysosomal enzymes. The total cellular response to silica found in the washout showed a pronounced increase when compared with either asbestos dust or controls; crocidolite gave a decreased response in an early group of the individual cells studied. The most important finding was a decrease in the number of mast cells found to be associated with the injection of both types of fibres. Crocidolite induced granulomas showed the presence of lysosomal enzymes and non-specific esterase in mononuclear cells and giant cells, even two years after injection. With chrysotile, giant cells were only present up to three to four months, and few positively staining cells were noted after 18 months. While the response of cells in the pleural cavity does not differ greatly between the two types of fibres, that in the granulomas highlights the longer lasting action of crocidolite.}, } @article {pmid6523093, year = {1984}, author = {Mowé, G and Gylseth, B and Hartveit, F and Skaug, V}, title = {Occupational asbestos exposure, lung-fiber concentration and latency time in malignant mesothelioma.}, journal = {Scandinavian journal of work, environment & health}, volume = {10}, number = {5}, pages = {293-298}, doi = {10.5271/sjweh.2326}, pmid = {6523093}, issn = {0355-3140}, mesh = {Aged ; Asbestos/*adverse effects/analysis ; Humans ; Lung/*ultrastructure ; Lung Neoplasms/*etiology/mortality ; Male ; Mesothelioma/*etiology/mortality ; Middle Aged ; Occupational Diseases/*etiology/mortality ; Time Factors ; }, abstract = {Mineral fiber concentration in lung tissue was analyzed by scanning electron microscopy in 73 males with malignant mesothelioma and in 36 referents who died of cardio- or cerebrovascular diseases. The investigation showed apparent differences in the median lung-fiber concentration between occupational groups with different levels of asbestos exposure, as judged from their occupational history. Thus the mineral fiber content in human lung tissue provides a useful indicator of cumulative asbestos exposure. There was also a statistically significant difference between the median lung-fiber concentration among mesothelioma cases with unlikely or unknown occupational asbestos exposure and the reference group. The latency times in 42 of the cases with definite or probable occupational asbestos exposure showed a log-normal distribution with a median of 37 years and a range of 19-68 years. No statistically significant correlation was found between the logarithm of the latency time and the logarithm of the lung-fiber concentration.}, } @article {pmid6504438, year = {1984}, author = {Polakoff, PL}, title = {Have we really stopped exposing workers to asbestos?.}, journal = {Occupational health & safety (Waco, Tex.)}, volume = {53}, number = {9}, pages = {61-62}, pmid = {6504438}, issn = {0362-4064}, mesh = {Asbestos/*adverse effects ; Asbestosis/etiology/*prevention & control ; Environmental Exposure ; Humans ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; United States ; }, } @article {pmid6393580, year = {1984}, author = {Zerbino, DD and Dmitruk, IM}, title = {[Etiology, pathogenesis and clinico-morphological characteristics of mesotheliomas (a review of the literature)].}, journal = {Vrachebnoe delo}, volume = {}, number = {10}, pages = {4-8}, pmid = {6393580}, issn = {0049-6804}, mesh = {Adolescent ; Adult ; Asbestos/adverse effects ; Asbestosis/complications ; Connective Tissue/pathology ; Epithelium/pathology ; Female ; Heart Neoplasms/epidemiology/etiology/pathology ; Humans ; Industrial Waste/adverse effects ; Male ; Mesothelioma/epidemiology/*etiology/pathology ; Middle Aged ; Occupational Diseases/epidemiology/etiology/pathology ; Pericardium ; Peritoneal Neoplasms/epidemiology/etiology/pathology ; Pleural Neoplasms/epidemiology/*etiology/pathology ; }, } @article {pmid6098009, year = {1984}, author = {Ohlson, CG and Klaesson, B and Hogstedt, C}, title = {Mortality among asbestos-exposed workers in a railroad workshop.}, journal = {Scandinavian journal of work, environment & health}, volume = {10}, number = {5}, pages = {283-291}, doi = {10.5271/sjweh.2329}, pmid = {6098009}, issn = {0355-3140}, mesh = {Aged ; Asbestos/*adverse effects ; Asbestos, Amphibole ; Asbestos, Serpentine ; Humans ; Lung Neoplasms/etiology ; Male ; Neoplasms/mortality ; Occupational Diseases/etiology/*mortality ; *Railroads ; Risk ; Silicon Dioxide/adverse effects ; Smoking ; Time Factors ; }, abstract = {The mortality experience of a cohort of 3 297 railroad maintenance shopworkers exposed to asbestos was investigated. The study period was 1951-1980, and the vital status was assessed for 99.6% of the men. Individual estimates of cumulative asbestos exposure were based on detailed records on work tasks and divisions. Dust measurements were scanty in earlier decades, and estimates of average fiber levels were therefore based on information on the amount and kind of asbestos used, job descriptions, and interviews with older workers. The overall mortality was lower than expected from the national death rates (standardized mortality ratio = 82). The mortality from lung cancer increased as cumulative exposure increased in consistent dose-response relationships. Employment times of less than 30 years in workplaces with moderate levels of mainly chrysotile asbestos was not associated with any apparent increase in the risk of lung cancer. A subgroup exposed for more than 30 years in workplaces repairing steam engines, where amphiboles were used as well, had a standardized mortality ratio of 192 for lung cancer. This figure may be an underestimation due to healthy worker selection and fewer smokers than normal. The "true" standardized mortality ratio was estimated to be about 300. Five cases of mesothelioma were observed.}, } @article {pmid6092048, year = {1984}, author = {Suzuki, Y and Kohyama, N}, title = {Malignant mesothelioma induced by asbestos and zeolite in the mouse peritoneal cavity.}, journal = {Environmental research}, volume = {35}, number = {1}, pages = {277-292}, doi = {10.1016/0013-9351(84)90136-1}, pmid = {6092048}, issn = {0013-9351}, support = {CA 24311/CA/NCI NIH HHS/United States ; CA 29432/CA/NCI NIH HHS/United States ; }, mesh = {*Aluminum Silicates ; Animals ; *Asbestos ; Asbestos, Amosite ; Asbestos, Serpentine ; Male ; Mesothelioma/*etiology/pathology ; Mice ; Mice, Inbred BALB C ; Neoplasms, Multiple Primary/etiology ; Peritoneal Neoplasms/*etiology/pathology ; Plasmacytoma/etiology ; Zeolites ; }, abstract = {The carcinogenicity of asbestos (amosite and chrysotile) and zeolite (fibrous erionite, mordenite, and synthetic zeolite 4A) were studied in the peritoneum of 586 BALB/C male mice after a single intraperitoneal or intraabdominal wall injection. As controls, 182 mice treated with and without saline solution were used. Both asbestos types and fibrous erionite frequently produced malignant peritoneal tumors after long latency; tumors developed in 93 of 394 animals (23.6%) treated with asbestos or fibrous erionite 7 months or more after administration. All of the induced peritoneal tumors were intimately associated with marked peritoneal fibrosis, in which asbestos or erionite fibers were regularly detected. Histopathologically, 83 (73 fibrous, 9 biphasic, and 1 epithelial) of 93 were consistent with malignant mesotheliomas. Other tumors consisted of 6 plasmacytomas, 1 histiocytoma, 1 liposarcoma, 1 osteosarcoma, and 1 adenocarcinoma of the pancreas. Two of the cases of mesotheliomas were associated with plasmacytoma. In many instances, the primary site of the mesotheliomas seemed to be multiple, the favorite sites being the omentum, mesentery, serosae of the gastrointestinal and genital organs, the diaphragm, the capsule of the liver and spleen, and the abdominal wall peritoneum. In these cases, asbestos or erionite-tissue burden followed by fibrosis was frequently observed. In addition to the 93 peritoneal tumors, 3 extraperitoneal tumors (1 fibrosarcoma and 2 rhabdomyosarcomas) were induced by amosite which was probably accidentally injected into the extraperitoneal connective tissue and the striated muscle tissue of the abdominal wall, respectively. These three tumors were also intimately associated with focal fibrosis in which amosite fibers were detected. Among the three different types of zeolite, only fibrous erionite showed striking carcinogenicity and marked fibrogenicity. The erionite-induced mesotheliomas were similar to those induced by asbestos in exhibiting long latency, in gross appearance, in histology, and in close association with fibrosis. Long-term persistence of asbestos or fibrous erionite around progenitor cells of the induced tumors and the consequent fibrosis seemed to be an important precondition of the malignant transformation of the progenitor cells.}, } @article {pmid6089062, year = {1984}, author = {Howard, JK}, title = {Relative cancer risks from exposure to different asbestos fibre types.}, journal = {The New Zealand medical journal}, volume = {97}, number = {764}, pages = {646-649}, pmid = {6089062}, issn = {0028-8446}, mesh = {Asbestos/*adverse effects ; Asbestos, Amosite ; Asbestos, Crocidolite ; Asbestos, Serpentine ; Canada ; Humans ; Lung Neoplasms/*etiology ; Maximum Allowable Concentration ; Mesothelioma/*etiology ; New Zealand ; Occupational Diseases/*etiology ; Risk ; South Africa ; United Kingdom ; United States ; }, } @article {pmid6484764, year = {1984}, author = {Solomons, K}, title = {Malignant mesothelioma--clinical and epidemiological features. A report of 80 cases.}, journal = {South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde}, volume = {66}, number = {11}, pages = {407-412}, pmid = {6484764}, issn = {0256-9574}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Female ; Humans ; Lung Neoplasms/*epidemiology/etiology ; Male ; Mediastinal Neoplasms/epidemiology/etiology ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Diseases/*epidemiology/etiology ; Prognosis ; Retrospective Studies ; South Africa ; Thoracic Neoplasms/epidemiology/etiology ; }, abstract = {The clinical and epidemiological features of 80 cases of malignant mesothelioma (as proved by examination of biopsy specimens) referred to the clinic at the National Centre for Occupational Health between January 1977 and June 1983 are reviewed. There was a positive history of asbestos exposure in 89% of cases. The mean survival time from diagnosis to death was 8,6 months and from the onset of symptoms to death 13,6 months. Survival time was unaffected by stage of the tumour, treatment, histological features, smoking status, presenting symptoms, presence or absence of effusion and asbestosis, side of the lesion, source of exposure and lag period from first exposure to diagnosis. The duration of survival was significantly affected by age at diagnosis, duration of asbestos exposure and the number, rather than the type, of treatment regimens used. Caution is advocated in interpreting these data since the number of cases was small and the study design was retrospective. A reference group of 546 cases notified over the same period was drawn from the records of the South African Asbestos Tumour Reference Panel. The incompleteness of national mesothelioma incidence data was noted, and an incidence figure of 7,2 per million per year was calculated from the best-available data for South Africa. This figure is an underestimate because not all diagnosed cases are reflected and, more important, significant numbers of cases are never diagnosed. The extent to which the compensation machinery functions is mentioned.}, } @article {pmid6331632, year = {1984}, author = {Peterson, JT and Greenberg, SD and Buffler, PA}, title = {Non-asbestos-related malignant mesothelioma. A review.}, journal = {Cancer}, volume = {54}, number = {5}, pages = {951-960}, doi = {10.1002/1097-0142(19840901)54:5<951::aid-cncr2820540536>3.0.co;2-a}, pmid = {6331632}, issn = {0008-543X}, mesh = {Aluminum Silicates/adverse effects ; Animals ; Asbestos/*adverse effects ; Avian Leukosis Virus ; Beryllium/adverse effects ; Carcinogens ; Chickens ; Cocarcinogenesis ; Disease Susceptibility ; Dust/adverse effects ; Female ; Humans ; Inflammation ; Male ; Mesothelioma/chemically induced/*etiology ; Metallurgy ; Mice ; Neoplasms, Radiation-Induced ; Nickel/adverse effects ; Occupational Diseases/chemically induced/etiology ; Peritoneal Neoplasms/chemically induced/*etiology ; Pleural Neoplasms/chemically induced/*etiology ; Rats ; Silicon Dioxide/adverse effects ; Smoking ; Zeolites ; }, abstract = {Malignant mesothelioma is an uncommon, but increasingly important, neoplasm. The existing English-language medical literature concerning non-asbestos-related malignant mesotheliomas was reviewed for evidence of other agents associated with the induction of malignant mesothelioma. Both animal and human data were reviewed. In most reviews of malignant mesothelioma, there are a significant proportion of cases without documented asbestos exposure (range, 0% to 87%). Furthermore, there are several fairly well-documented agents other than asbestos that induce malignant mesothelioma in animals, and strong evidence exists that such is the case in man. In reviews of malignant mesothelioma, the percentage of cases with asbestos exposure varies, but a significant number are apparently not asbestos related. It is believed that sufficient evidence exists to suggest that non-asbestos agents can induce malignant mesotheliomas in man, and additional epidemiologic studies in this area are needed.}, } @article {pmid6474389, year = {1984}, author = {Hillerdal, G and Zitting, A and van Assendelft, AH and Kuusela, T}, title = {Rarity of mineral fibre pleurisy among persons exposed to Finnish anthophyllite and with low risk of mesothelioma.}, journal = {Thorax}, volume = {39}, number = {8}, pages = {608-611}, pmid = {6474389}, issn = {0040-6376}, mesh = {Adolescent ; Adult ; Asbestos/*adverse effects ; *Asbestos, Amphibole ; Female ; Finland ; Humans ; Male ; Mesothelioma/etiology ; Middle Aged ; Pleural Neoplasms/etiology ; Pleurisy/*etiology ; Risk ; Turkey ; }, abstract = {Endemic pleural plaques are reported from many parts of the world. In Central Europe and in Finland no connection with malignant mesotheliomas has been found, whereas this tumour is often encountered in areas in Turkey where endemic plaques also occur. There seem, however, to be differences in the radiological appearances found in these areas. In the present study chest radiographs of 317 persons with pleural plaques from the endemic area of Finland were scrutinized. It was found that 4.7% showed a blunted costophrenic angle unilaterally and 0.9% bilaterally. The prevalence of sequelae of pleurisy is statistically very highly significantly lower than in people with pleural plaques in Turkey. As the risk of mesothelioma appears to be low in Finland, the results are in accordance with the hypothesis that the risk of mesothelioma in a given population is higher if in that population there is a high incidence of benign asbestos pleurisy.}, } @article {pmid6738440, year = {1984}, author = {Gandevia, B}, title = {Mesothelioma.}, journal = {The Medical journal of Australia}, volume = {141}, number = {2}, pages = {80}, pmid = {6738440}, issn = {0025-729X}, mesh = {Asbestos/adverse effects ; Australia ; Humans ; Mesothelioma/*epidemiology/etiology ; Occupational Diseases/epidemiology/etiology ; Wales ; }, } @article {pmid6330509, year = {1984}, author = {Armstrong, BK and Musk, AW and Baker, JE and Hunt, JM and Newall, CC and Henzell, HR and Blunsdon, BS and Clarke-Hundley, MD and Woodward, SD and Hobbs, MS}, title = {Epidemiology of malignant mesothelioma in Western Australia.}, journal = {The Medical journal of Australia}, volume = {141}, number = {2}, pages = {86-88}, pmid = {6330509}, issn = {0025-729X}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Asbestos, Crocidolite ; Australia ; Female ; Humans ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Diseases/epidemiology/etiology ; Peritoneal Neoplasms/*epidemiology/etiology ; Pleural Neoplasms/*epidemiology/etiology ; Time Factors ; }, abstract = {Crocidolite was mined and milled at Wittenoom Gorge in Western Australia from 1943 to 1966. Between 1960-1964 and 1980-1982, the estimated incidence of malignant mesothelioma in Western Australia rose from 0.6/100 000 in men and less than 0.1/100 000 in women, aged 35 years or older, to 6.6/100 000 in men and 0.7/100 000 in women in this age group. Overall, 97 (70%) of 138 patients with malignant mesothelioma had definite or probable exposure to asbestos; 76 of these (55%) to Western Australian crocidolite. Of the latter 76 patients, 56 had worked in the mine or mill at Wittenoom and 4 had non-occupational exposure in the Wittenoom area; the remaining 16 had been exposed to crocidolite elsewhere in the State. There were only 4 (3%) patients with malignant peritoneal mesothelioma, of whom three had been exposed to crocidolite.}, } @article {pmid6327010, year = {1984}, author = {Antman, KH and Ruxer, RL and Aisner, J and Vawter, G}, title = {Mesothelioma following Wilms' tumor in childhood.}, journal = {Cancer}, volume = {54}, number = {2}, pages = {367-369}, doi = {10.1002/1097-0142(19840715)54:2<367::aid-cncr2820540232>3.0.co;2-y}, pmid = {6327010}, issn = {0008-543X}, mesh = {Adult ; Child ; Combined Modality Therapy ; Humans ; Kidney Neoplasms/*radiotherapy ; Male ; Mesothelioma/*etiology/pathology ; Neoplasms, Radiation-Induced/*pathology ; Pleural Neoplasms/*etiology/pathology ; Triethylenemelamine/therapeutic use ; Wilms Tumor/*radiotherapy ; }, abstract = {A high percentage of children with Wilms' tumor are cured with multimodal treatment. A small percentage of these children will develop second tumors, perhaps related to a genetic predisposition to neoplasia or possibly secondary to the treatment utilized for Wilms' tumor. Malignant mesothelioma has been associated with contact with asbestos but has also been reported after radiation exposure. Two patients are reported who developed malignant mesothelioma of the pleura after treatment for Wilms' tumor in childhood. Both received orthovoltage radiation; one patient also received triethylenemelamine (TEM), an alkylating agent closely related to nitrogen mustard, for 5 years. Factors in the development of second tumors are discussed.}, } @article {pmid6428677, year = {1984}, author = {Browne, K and Goffe, T}, title = {Mesothelioma due to domestic exposure to asbestos.}, journal = {British medical journal (Clinical research ed.)}, volume = {289}, number = {6437}, pages = {110-111}, pmid = {6428677}, issn = {0267-0623}, mesh = {Asbestos/*adverse effects ; Female ; Humans ; Mesothelioma/*etiology ; Pleural Neoplasms/*etiology ; }, } @article {pmid6727012, year = {1984}, author = {Fischbein, A and Rohl, AN}, title = {Pleural mesothelioma and neighborhood asbestos exposure. Findings from microchemical analysis of lung tissue.}, journal = {JAMA}, volume = {252}, number = {1}, pages = {86-87}, pmid = {6727012}, issn = {0098-7484}, mesh = {Asbestos/*adverse effects/analysis ; Environmental Exposure ; Humans ; Lung/analysis ; Male ; Mesothelioma/analysis/*etiology ; Middle Aged ; Pleural Neoplasms/analysis/*etiology ; }, } @article {pmid6379132, year = {1984}, author = {Whitaker, D and Shilkin, KB}, title = {Diagnosis of pleural malignant mesothelioma in life--a practical approach.}, journal = {The Journal of pathology}, volume = {143}, number = {3}, pages = {147-175}, doi = {10.1002/path.1711430303}, pmid = {6379132}, issn = {0022-3417}, mesh = {Adenocarcinoma/pathology/secondary ; Biopsy, Needle ; Cell Aggregation ; Diagnosis, Differential ; Fibroblasts/pathology ; Humans ; Lymphocytes/pathology ; Mesothelioma/*diagnosis/pathology ; Methods ; Microscopy, Electron ; Pleural Effusion ; Pleural Neoplasms/*diagnosis/pathology/secondary ; }, abstract = {This review documents a practical approach to the pathological diagnosis of pleural malignant mesothelioma based on the closed needle biopsy and effusion cytology, thus avoiding the need to resort to open surgery. Tissue diagnosis is often difficult, and the pathologist's opinion may be influenced by a consideration of three factors: the clinical setting; the adequacy and availability of specimens; and the criteria for assessment and interpretation of these. The level of confidence with which a tissue diagnosis of mesothelioma can be established using limited material depends on there being an appropriate clinical background including a history of asbestos exposure. Without this, the diagnosis should be a qualified or tentative one. For an adequate tissue sample to be obtained, the closed needle biopsy procedure is best performed by an experienced operator. All aspirated pleural effusions should be forwarded for cytological evaluation. In addition to conventional morphological studies, adequate samples permit ancillary tests to be carried out. A combined interpretive approach utilizing both histopathology and cytology is recommended in order to increase the accuracy of the diagnosis.}, } @article {pmid6475155, year = {1984}, author = {Bittersohl, G}, title = {[Epidemiology of sequelae of asbestos dust inhalation in the chemical industry].}, journal = {Zeitschrift fur die gesamte Hygiene und ihre Grenzgebiete}, volume = {30}, number = {6}, pages = {319-320}, pmid = {6475155}, issn = {0049-8610}, mesh = {Asbestosis/*epidemiology ; Carcinoma, Bronchogenic/epidemiology ; Chemical Industry ; Dust/*adverse effects ; Germany, East ; Humans ; Lung Neoplasms/*epidemiology ; Mesothelioma/epidemiology ; }, } @article {pmid6329002, year = {1984}, author = {Churg, A and Wiggs, B}, title = {Fiber size and number in amphibole asbestos-induced mesothelioma.}, journal = {The American journal of pathology}, volume = {115}, number = {3}, pages = {437-442}, pmid = {6329002}, issn = {0002-9440}, mesh = {Aged ; Asbestos/adverse effects/*analysis ; Asbestos, Amosite ; Asbestos, Amphibole ; Asbestos, Crocidolite ; Female ; Humans ; Lung/analysis ; Male ; Mesothelioma/*analysis/etiology ; Middle Aged ; Occupational Diseases/etiology/*metabolism ; Particle Size ; Pleural Neoplasms/*analysis/etiology ; Silicon Dioxide/adverse effects/*analysis ; }, abstract = {Numbers and sizes of fibers from the lungs of 10 patients who had an amphibole asbestos-induced malignant pleural mesothelioma were analyzed. Amosite was found in 10 lungs and crocidolite in 9; the average ratio of amosite to crocidolite was approximately 14:1. In the 8 patients who were not long-time asbestos insulators , the mean number of amosite fibers was 2.3 X 10(6) fibers/g dry lung, and of crocidolite fibers, 0.2 X 10(6)/g; these values represent an approximately 250-fold increase over those found in the general population. Crocidolite fibers were significantly narrower than amosite fibers (mean width, 0.13 versus 0.23 mu), were significantly shorter (mean length, 4.0 versus 5.8 mu), and had a significantly higher mean aspect (length to width) ratio (48 versus 34). Aspect ratios in general increased with increasing fiber length and decreasing fiber width, but the highest values were found for thin amosite fibers at about 13 mu in length, and thin crocidolite fibers at 8 or 15-17 mu in length. Comparison with data from other asbestos-exposed populations indicates that mesothelioma can be induced by relatively small numbers of amphibole fibers and also indicates that amosite is an effective mesothelial carcinogen in humans. Comparison of these data with epidemiologic and experimental predictions of carcinogenic size ranges for mesothelioma induction implies that either the carcinogenic size range is much broader than has been claimed (in particular, fibers considerably shorter than 8 mu and broader than 0.05 mu can produce mesothelioma), or, alternately, that extraordinarily small absolute numbers of fibers in certain size ranges can induce tumors in humans.}, } @article {pmid6204669, year = {1984}, author = {Johnson, NF and Edwards, RE and Munday, DE and Rowe, N and Wagner, JC}, title = {Pluripotential nature of mesotheliomata induced by inhalation of erionite in rats.}, journal = {British journal of experimental pathology}, volume = {65}, number = {3}, pages = {377-388}, pmid = {6204669}, issn = {0007-1021}, mesh = {Aluminum Silicates/*toxicity ; Animals ; Keratins/analysis ; Mesothelioma/analysis/*etiology/ultrastructure ; Microscopy, Electron ; Phosphopyruvate Hydratase/analysis ; Pleural Neoplasms/analysis/*etiology/ultrastructure ; Rats ; Zeolites ; }, abstract = {Mesotheliomata can be induced more rapidly and more frequently by inhalation of erionite than by asbestos inhalation. Erionite-induced tumours have in general a similar ultrastructural appearance to inoculum-induced pleural and peritoneal mesotheliomata. Unusual features of these tumours were the presence of dense-cored vesicles and cells staining positively for neuron-specific enolase which indicated the presence of endocrine cells. In addition, one tumour showed differentiation towards bone-forming cells. The expression of both epithelial and mesodermal characteristics demonstrates the pluripotential nature of mesothelial cells under certain circumstances.}, } @article {pmid6735320, year = {1984}, author = {Heitz, M and Herzog, H}, title = {[Lung diseases in the elderly. Pathogenetic significance of pollutants and environmental factors].}, journal = {Fortschritte der Medizin}, volume = {102}, number = {17}, pages = {477-482}, pmid = {6735320}, issn = {0015-8178}, mesh = {Age Factors ; Aged ; Air Pollution/*adverse effects ; Asbestos/adverse effects ; Bronchitis/etiology ; Environmental Pollutants/*adverse effects ; Humans ; Lung Diseases/*etiology ; Lung Diseases, Obstructive/therapy ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Oxygen Inhalation Therapy ; Pulmonary Emphysema/etiology ; Tobacco Smoke Pollution/adverse effects ; }, abstract = {In the elderly pneumoconioses due to anorganic or organic dusts are not very common. The incidence of mesothelioma is increasing also in the elderly population. Mesothelioma has become the most frequent occupational malignancy. There is also evidence that mesothelioma can be produced by other fibers than asbestos particles. The paper discusses further the effect of passive smoking, where there is new evidence that passive-smokers are exposed to a higher risk for bronchial cancer than non-smokers. The interactions between smoking and air pollution and morbidity of chronic bronchitis are illustrated. New aspects of pathogenesis and pathophysiology of chronic obstructive lung disease and pulmonary emphysema due to smoking as the most frequent environmental lung disease in the elderly are further discussed. A brief overview of the therapeutical approach to chronic obstructive lung disease including new forms of treatment of cor pulmonale is finally given.}, } @article {pmid6726298, year = {1984}, author = {Antman, K and Cohen, S and Dimitrov, NV and Green, M and Muggia, F}, title = {Malignant mesothelioma of the tunica vaginalis testis.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {2}, number = {5}, pages = {447-451}, doi = {10.1200/JCO.1984.2.5.447}, pmid = {6726298}, issn = {0732-183X}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Castration ; Combined Modality Therapy ; Humans ; Laparotomy ; Male ; Mesothelioma/etiology/radiotherapy/*surgery ; Middle Aged ; Neoplasm Recurrence, Local ; Testicular Neoplasms/etiology/radiotherapy/*surgery ; Time Factors ; Wounds, Nonpenetrating/complications ; }, abstract = {Eighteen patients with malignant mesothelioma of the tunica vaginalis testis have been previously reported. These and the six patients reported here are reviewed for natural history and response to treatment. This tumor should be considered in men of any age with scrotal masses that include a hydrocele. Staging procedures should include computerized tomography scanning of the chest and abdomen. Inguinal orchiectomy appears to be the optimal primary surgical approach. Intraabdominal disease found at diagnostic laparotomy may be effectively treated by surgery and/or abdominal radiotherapy. Clinical features such as a long asymptomatic interval from initial presentation to clinical recurrence were observed and are also worthy of emphasis. Thus, serial follow-up is advised. Upon recurrence, treatment remains unsatisfactory but some responsiveness to chemotherapy has been noted. Doxorubicin-containing regimens were administered to five patients with measurable pulmonary nodules resulting in two partial regressions by standard criteria.}, } @article {pmid6494110, year = {1984}, author = {Richter, ED and Tulchinsky, T and Goldsmith, JR and Yaffe, Y}, title = {Asbestos-exposed populations: prevention, care, and compensation.}, journal = {Preventive medicine}, volume = {13}, number = {3}, pages = {286-298}, doi = {10.1016/0091-7435(84)90085-9}, pmid = {6494110}, issn = {0091-7435}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Asbestosis/prevention & control ; Female ; *Health Policy ; Humans ; Israel ; Lung Neoplasms/etiology ; Male ; Maximum Allowable Concentration ; Mesothelioma/etiology ; Middle Aged ; Occupational Diseases/economics/*etiology/prevention & control ; Risk ; Smoking Prevention ; }, abstract = {In Israel, the prevention and care of asbestos-associated diseases with latency periods of one to four decades (asbestosis, mesothelioma, increased frequency of cancer of the lung and other sites) are not satisfactory, and new national policies are required. Such policies have three major goals: (a) elimination or reduction of exposure to asbestos dust; (b) measures to promote cessation or drastic reduction of cigarette smoking among those currently or formerly exposed; and (c) equitable compensation for the consequences of past exposures. The practical elements of a program to achieve these three goals include (a) exposure standards and control technology; (b) identification of sources, routes, and levels of exposure and groups at risk; (c) compensation and job security; (d) medical monitoring and follow-up; (e) smoking cessation; (f) selective substitution of other substances for asbestos; and (g) establishment of a panel for policy supervision and the overseeing of compensation programs. Delay in implementation risks higher death rates for asbestosis and cancer among previously exposed workers, greater exposure among current workers, loss of experienced workers from the work force, and unnecessary hardship for families not adequately compensated.}, } @article {pmid6326794, year = {1984}, author = {McDonald, AD and Fry, JS and Woolley, AJ and McDonald, JC}, title = {Dust exposure and mortality in an American chrysotile asbestos friction products plant.}, journal = {British journal of industrial medicine}, volume = {41}, number = {2}, pages = {151-157}, pmid = {6326794}, issn = {0007-1072}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Asbestos, Amphibole ; Asbestos, Serpentine ; Asbestosis/mortality ; Connecticut ; Environmental Exposure ; Humans ; Lung Neoplasms/etiology/mortality ; Male ; Mesothelioma/etiology/mortality ; Middle Aged ; Occupational Diseases/*mortality ; Pennsylvania ; Pneumoconiosis/mortality ; Silicon Dioxide/adverse effects ; South Carolina ; Textile Industry ; }, abstract = {Cohort studies in three American asbestos factories were undertaken to investigate the effect of fibre type and manufacturing process on lung cancer, mesothelioma, and asbestosis. Reports have been published on a chrysotile textile plant in South Carolina and a mainly textile plant in Pennsylvania, which also used amphiboles. In the third plant in Connecticut friction products and packings were made from chrysotile only. In a cohort of 3641 men employed for one month or more, 1938-58, 3513 (96.5%) were traced, 1267 (36%) had died, and death certificates were obtained for 1228 (96.9%). Individual exposures were estimated (in mcpf . years) from impinger measurements. Life table analyses using Connecticut mortality rates gave an SMR for all causes of 108.5 (USA 107.9). The SMR (all causes) for men who had worked for less than a year was 129.9 and for those who had worked for a year or more, 101.2. The equivalent SMRs for respiratory cancer were 167.4 and 136.7 respectively. Excluding men who had worked for less than a year, there was possible evidence of some increase in risk of lung cancer with increasing exposure, supported also by a "log-rank" (case-control) analysis, of the same order as that observed in chrysotile mining and milling. These findings may be compared with chrysotile textile manufacture where the risk of lung cancer was some 50-fold greater. It is suggested that the differences in risk are perhaps related to the higher proportion of submicroscopic fibres in textile manufacture that may result from the traumatic carding , spinning, and weaving processes. No case of mesothelioma was found, consistent with a much lower risk of this tumour with chrysotile than with amphiboles. Twelve deaths (nine in men with very short and low asbestos exposure) were given ICD code 523 (pneumoconiosis); all but two were ascribed to anthracosilicosis or silicosis and none to asbestosis.}, } @article {pmid6326627, year = {1984}, author = {Finkelstein, MM}, title = {Mortality among employees of an Ontario asbestos-cement factory.}, journal = {The American review of respiratory disease}, volume = {129}, number = {5}, pages = {754-761}, doi = {10.1164/arrd.1984.129.5.754}, pmid = {6326627}, issn = {0003-0805}, mesh = {Adenocarcinoma/etiology/mortality ; Adult ; Aged ; Asbestos/*adverse effects ; Carcinoma, Small Cell/etiology/mortality ; Carcinoma, Squamous Cell/etiology/mortality ; Construction Materials/adverse effects ; Epidemiologic Methods ; Gastrointestinal Neoplasms/etiology/mortality ; Humans ; Lung Neoplasms/etiology/*mortality ; Male ; Mesothelioma/etiology/*mortality ; Middle Aged ; Occupational Diseases/etiology/*mortality ; Ontario ; Risk ; Time Factors ; }, abstract = {Mortality among 535 asbestos-exposed and 205 nonexposed employees of an asbestos-cement factory was investigated. In the period beyond 20 yr from first exposure, the exposed workers had standardized mortality ratios of 175 for all causes of death, 370 for all malignancies, 480 for lung cancer, 240 for gastrointestinal cancers, and 17 deaths from mesothelioma; the factory control subjects had mortality rates similar to the general population. The cell-type distribution of the lung cancers was similar to that occurring in middle-aged smokers. Cumulative fiber exposures were calculated for the production workers, and mortality rates for the asbestos-associated malignancies were found to have significant trends with exposure. Exposure-related lung cancer risks were noted, with a large margin of uncertainty, to be similar to those observed in an American study of manmade mineral fiber workers.}, } @article {pmid6324999, year = {1984}, author = {Hesterberg, TW and Barrett, JC}, title = {Dependence of asbestos- and mineral dust-induced transformation of mammalian cells in culture on fiber dimension.}, journal = {Cancer research}, volume = {44}, number = {5}, pages = {2170-2180}, pmid = {6324999}, issn = {0008-5472}, mesh = {Animals ; Asbestos/*adverse effects ; Asbestos, Crocidolite ; Asbestos, Serpentine ; Cell Transformation, Neoplastic/*etiology ; Cells, Cultured ; Cricetinae ; Dose-Response Relationship, Drug ; Dust/*adverse effects ; Embryo, Mammalian ; Glass ; Mesocricetus ; Microscopy, Electron ; Minerals/*adverse effects ; Quartz/adverse effects ; }, abstract = {The abilities of chrysotile and crocidolite asbestos, glass fibers of differing dimensions, and nonfibrous mineral particulates to induce morphological transformation of Syrian hamster embryo cells in culture were compared. Chrysotile and crocidolite asbestos induced morphologically transformed colonies which were indistinguishable from transformed colonies observed following treatment with known chemical carcinogens. A linear, dose-dependent increase in the frequency of transformed colonies was observed. The slope of the dose-response curve on a log-log scale was approximately 1, which is consistent with a one-hit mechanism for their induction. The transforming potency of chrysotile asbestos was decreased by milling of the fibers but not by extraction with an organic solvent. Chrysotile asbestos was nearly twice as potent in inducing morphological transformation as crocidolite asbestos. Glass fibers were also very active in this assay. Thin glass fibers with an average diameter of 0.1 to 0.2 micrometer were as active as asbestos. In contrast, two nonfibrous particulates, alpha-quartz and Min-U-Sil, were inactive over the same concentration range used for the fibrous dusts; however, both were active at higher doses. The effect of varying fiber dimension on induction of morphological transformation was examined with glass fibers. When compared on a per-weight basis, thick glass fibers [average diameter, 0.8 plus/minus 0.06 micrometer (S.E.)] were 20-fold less potent than thin fibers [average diameter, 0.13 plus/minus 0.005 micrometer] in inducing cell transformation. When the average fiber length of thin glass fibers was reduced from 9.5 to 1.7 micrometer by milling the fibers in a mortar and pestle, a 10-fold decrease in transforming activity resulted. When the average fiber length was reduced to 0.95 micrometer, transforming ability was totally absent. The cytotoxic potencies of the various mineral dusts correlated with their transforming potencies. The varying abilities of the mineral dusts to induce cell transformation in vitro are similar to their abilities to induce mesotheliomas in vivo. Thus, this system provides a unique model for studying the mechanism of mineral fiber tumorigenesis and for comparing the relative risks of mineral dusts.}, } @article {pmid6708871, year = {1984}, author = {Barnes, R and Rogers, AJ}, title = {Unexpected occupational exposure to asbestos.}, journal = {The Medical journal of Australia}, volume = {140}, number = {8}, pages = {488-490}, doi = {10.5694/j.1326-5377.1984.tb108170.x}, pmid = {6708871}, issn = {0025-729X}, mesh = {Adult ; Asbestosis/diagnosis/*etiology ; Female ; Humans ; Mesothelioma/diagnosis/*etiology ; Pleural Neoplasms/diagnosis/*etiology ; Talc/*adverse effects ; }, abstract = {A 44-year-old woman with mesothelioma of the pleura presented for possible compensation to the Workers' Compensation (Dust Diseases) Board of New South Wales. No obvious asbestos exposure could be obtained from examination of the occupational history, yet examination of lung tissue revealed the presence of elevated levels of brown asbestos (amosite).}, } @article {pmid6708860, year = {1984}, author = {Ng, TK}, title = {Talc and mesothelioma.}, journal = {The Medical journal of Australia}, volume = {140}, number = {8}, pages = {452-453}, doi = {10.5694/j.1326-5377.1984.tb108157.x}, pmid = {6708860}, issn = {0025-729X}, mesh = {Asbestos/*adverse effects ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; Talc/*adverse effects ; }, } @article {pmid6723827, year = {1984}, author = {Mårtensson, G and Larsson, S and Zettergren, L}, title = {Malignant mesothelioma in two pairs of siblings: is there a hereditary predisposing factor?.}, journal = {European journal of respiratory diseases}, volume = {65}, number = {3}, pages = {179-184}, pmid = {6723827}, issn = {0106-4339}, mesh = {Aged ; Asbestos/adverse effects ; *Diseases in Twins ; Humans ; Male ; Mesothelioma/etiology/*genetics/pathology ; Middle Aged ; Pleural Neoplasms/etiology/*genetics/pathology ; Smoking ; }, abstract = {Two pairs of siblings with malignant pleural mesothelioma are reported. One sister and brother experienced slight household asbestos exposure during childhood. Two identical-twin brothers were occupationally exposed to asbestos for only 8 years. The occurrence of this rare neoplasm in 2 pairs of siblings indicates that a hereditary predisposing factor may exist.}, } @article {pmid6723826, year = {1984}, author = {Mårtensson, G and Hagmar, B and Zettergren, L}, title = {Diagnosis and prognosis in malignant pleural mesothelioma: a prospective study.}, journal = {European journal of respiratory diseases}, volume = {65}, number = {3}, pages = {169-178}, pmid = {6723826}, issn = {0106-4339}, mesh = {Aged ; Asbestos/adverse effects ; Biopsy, Needle ; Cytodiagnosis ; Environmental Exposure ; Female ; Humans ; Hyaluronic Acid/analysis ; Male ; Mesothelioma/*diagnosis/etiology/pathology ; Middle Aged ; Pleural Neoplasms/*diagnosis/etiology/pathology ; Prognosis ; Prospective Studies ; Sex Ratio ; Smoking ; Thoracoscopy ; Time Factors ; }, abstract = {In a prospective study of 336 consecutive patients with long-term pleural effusions, 32 cases of malignant mesothelioma were found. Microscopic examination of pleural tissue specimens, preferably selected at thoracoscopy, proved superior to pleural fluid analysis as an aid to correct diagnosis. The epithelial proved to be the most common type of malignant mesothelioma. As an example of the mesothelial cells' multipotent ability, malignant cells were seen transforming into fat-like cells with lipid-containing vacuoles. In the fibrous tumour type, cytological examination of pleural fluid revealed only normal cells. Cells with malignant features were seen in fluid samples from epithelial and biphasic tumour types. The malignant cells often formed tubuli-like aggregates which could be mistaken for adenocarcinoma. Hyaluronic acid was more frequently detected in tissue specimens than in the pleural fluid samples. The morphological type and the patient's age had an impact on the survival time, whereas sex and extensive surgical treatment seemed less important.}, } @article {pmid6723825, year = {1984}, author = {Dunnill, MS}, title = {Pleural mesothelioma.}, journal = {European journal of respiratory diseases}, volume = {65}, number = {3}, pages = {159-161}, pmid = {6723825}, issn = {0106-4339}, mesh = {Asbestos/adverse effects ; Humans ; Mesothelioma/etiology/*pathology ; Pleural Neoplasms/etiology/*pathology ; }, } @article {pmid6324841, year = {1984}, author = {Wagner, JC and Griffiths, DM and Hill, RJ}, title = {The effect of fibre size on the in vivo activity of UICC crocidolite.}, journal = {British journal of cancer}, volume = {49}, number = {4}, pages = {453-458}, pmid = {6324841}, issn = {0007-0920}, mesh = {Animals ; Asbestos/*toxicity ; Asbestos, Crocidolite ; Female ; Granuloma/etiology ; Male ; Mesothelioma/*etiology ; Microscopy, Electron ; Particle Size ; Pleural Diseases/etiology ; Pleural Neoplasms/*etiology ; Rats ; Rats, Inbred F344 ; Time Factors ; }, abstract = {Standard (UICC) crocidolite was subjected to ball milling to reduce the length of the fibre. These milled materials and the original standard sample were injected into the pleural cavity of rats to determine their ability to induce mesothelioma. Previous in vitro work on the same materials had suggested that biological activity was related to fibres greater than 6.5 microns in length and that the material milled for 4 and 8 h did not contain fibres in this range and was biologically inactive. The results of the animal work, however, did not follow this pattern; mesotheliomas occurred in rats in all treatment groups including the 4 and 8 h milled samples. Examination of the tissues and the dust recovered from them showed the presence of fibres greater than the suggested threshold. Attention is drawn to the problems associated with drawing conclusions from size distributions and in vitro studies without considering in vivo mechanisms.}, } @article {pmid6093677, year = {1984}, author = {McDonald, JC}, title = {Mineral fibres and cancer.}, journal = {Annals of the Academy of Medicine, Singapore}, volume = {13}, number = {2 Suppl}, pages = {345-352}, pmid = {6093677}, issn = {0304-4602}, mesh = {Asbestos/*adverse effects ; Asbestos, Amphibole ; Asbestos, Serpentine ; Asbestosis/*etiology ; Cocarcinogenesis ; Dust/adverse effects ; Humans ; Industry ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Pleural Diseases/etiology ; Pulmonary Fibrosis/etiology ; Silicon Dioxide/adverse effects ; }, abstract = {A synthesis is presented of the salient findings to date from laboratory and epidemiological research, on the health effects of asbestos and other natural and man-made mineral fibres. Experimental evidence suggests that all mineral fibres are capable of causing fibrosis and malignancy, with chrysotile at least as pathogenic as other fibres. However, penetration, retention and phagocytosis are affected by size and shape and reactivity and durability by physico-chemical properties. Thus it is not surprising that in man the results of exposure vary considerably with fibre type and industrial process. A considerable body of evidence suggests that chrysotile has seldom, if ever, caused peritoneal mesothelioma and that the great majority of pleural mesotheliomas are also attributable to crocidolite or amosite. Without more reliable information on intensity and duration of exposure by fibre type, the epidemiological evidence on this point cannot be wholly conclusive. There are stronger grounds from a limited number of cohort studies for believing that in relation to estimated exposure, the risk of lung cancer has been much higher in textile plants than in fibre production or in the manufacture of friction products, with asbestos-cement plants somewhere in between. The data on man-made fibre production remains equivocal. It is concluded that attempts to regulate asbestos without regard for fibre type, although perhaps adequate for lung cancer and fibrosis, may do little to reduce the risk of mesothelioma. The search for safe fibre substitutes for asbestos will remain difficult until the parameters of pathogenicity are better understood.}, } @article {pmid6583581, year = {1984}, author = {Cooke, KR}, title = {Deaths from asbestos-related diseases.}, journal = {The New Zealand medical journal}, volume = {97}, number = {752}, pages = {202}, pmid = {6583581}, issn = {0028-8446}, mesh = {Asbestosis/*mortality ; Humans ; Lung Neoplasms/*mortality ; Mesothelioma/*mortality ; New Zealand ; }, } @article {pmid6697895, year = {1984}, author = {Woitowitz, HJ and Paur, R and Breuer, G and Rödelsperger, K}, title = {[Mesothelioma as an index tumor of the occupational hazard of asbestos dust].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {109}, number = {10}, pages = {363-368}, doi = {10.1055/s-2008-1069196}, pmid = {6697895}, issn = {0012-0472}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Female ; Humans ; Male ; Mesothelioma/*etiology/pathology ; Middle Aged ; *Occupational Diseases/*etiology ; Peritoneal Neoplasms/*etiology/pathology ; Pleural Neoplasms/*etiology/pathology ; Time Factors ; }, abstract = {Mesothelioma arises from the cover epithelia of the serous body cavities and is a most malignant and fatal tumour. Since 1978 42 cases of diffusely growing mesothelioma have been observed. An extreme difference in the expected frequency of mesothelioma among previously severely asbestos-dust-exposed persons and the rest of the population is characteristic. Accordingly, death from mesothelioma does not only show a predominantly high occupational asbestos-dust-risk association but also to environmental exposition by neighborhood and household contact. Thus in production and use of asbestos-containing products a risk must be expected. Due to the great likelihood of asbestos-induced mesothelioma in the individual case it is justified to consider this tumour as signal for asbestos exposition decades ago. In the German Federal Republic "pleural and peritoneal mesothelioma caused by asbestos" is a notifiable occupational disease since 1977. Each diagnosis of mesothelioma initiates the suspicion and thus the medical duty of notification of an occupational disease. Following the large increase of asbestos consumption in the GFR over the last 30 years an increase of medically confirmed mesotheliomas can be expected.}, } @article {pmid6725448, year = {1984}, author = {Dubost, C and Charbonnier, JY and Assens, P and Garin, B and Jeunehomme, G and Lavergne, A and Abelanet, R and Le Charpentier, Y}, title = {[Giant fibroma of the pleura. Apropos of 2 cases].}, journal = {Journal de chirurgie}, volume = {121}, number = {3}, pages = {175-181}, pmid = {6725448}, issn = {0021-7697}, mesh = {Adult ; Female ; Fibroma/diagnosis/diagnostic imaging/*pathology ; Humans ; Middle Aged ; Pleural Neoplasms/diagnosis/diagnostic imaging/*pathology ; Radiography ; }, abstract = {Two cases are reported of giant pleural fibroma (2.9 and 4.2 kg), of slow growth (both had been present for 17 years), developing in the parietal pleura in a 56-year-old woman and in the triangular ligament of a 35-year-old man respectively, and treated by surgical excision. Findings in these cases and data on those reported in the literature indicate the principal pathologic and clinical characteristics of these very rare benign tumors of the pleura: onset in the absent of any history of exposure to dust (asbestos); usually fortuitous discovery; suggestive radiological appearances (calcification in some cases) that are not pathognomonic however; differentiation from fibrous mesothelioma by the microscopic or particularly gross pathologic appearance; treatment exclusively surgical and of variable difficulty according to the size of and especially the structures related to the tumor, with the need for careful preoperative screening.}, } @article {pmid6698701, year = {1984}, author = {Acheson, ED and Gardner, MJ and Winter, PD and Bennett, C}, title = {Cancer in a factory using amosite asbestos.}, journal = {International journal of epidemiology}, volume = {13}, number = {1}, pages = {3-10}, doi = {10.1093/ije/13.1.3}, pmid = {6698701}, issn = {0300-5771}, mesh = {Adult ; Asbestos/*adverse effects ; Epidemiologic Methods ; Humans ; London ; Lung Neoplasms/mortality ; Male ; Middle Aged ; Neoplasms/epidemiology/*etiology/mortality ; Occupational Diseases/epidemiology/*etiology/mortality ; Smoking ; }, abstract = {The paper describes the mortality experience of 5969 men employed in a factory where insulation board was manufactured using amosite asbestos from 1947 to 1979. 422 (7%) of the men were known to have died by the end of 1980. Among the 4820 men engaged in the manufacture of insulation board a doubling of the risk of lung cancer has occurred (57 deaths observed; 29 deaths expected). An excess is present both in men who entered the factory before and after 1960. Among the 2461 for whom smoking information is available a detectable excess risk is limited to current smokers exposed to higher levels of asbestos. Apart from five deaths from mesothelioma no statistically large or significant excesses of mortality from cancers of other sites have occurred, but further follow-up of the cohort is in progress. Nine deaths from asbestosis have been recorded. The results are discussed in the light of other studies of the effects of exposure to amosite asbestos.}, } @article {pmid6583973, year = {1984}, author = {Whitaker, D and Shilkin, KB and Walters, MN}, title = {Cytologic and tissue culture characteristics of asbestos-induced mesothelioma in rats.}, journal = {Acta cytologica}, volume = {28}, number = {2}, pages = {185-189}, pmid = {6583973}, issn = {0001-5547}, mesh = {Animals ; Asbestos/*adverse effects ; Cell Aggregation ; Cells, Cultured/ultrastructure ; Collagen/analysis ; Cytoskeleton/ultrastructure ; Intercellular Junctions/ultrastructure ; Male ; Mesothelioma/analysis/etiology/*pathology ; Microvilli/ultrastructure ; Pleural Effusion ; Pleural Neoplasms/etiology/*pathology ; Rats ; Rats, Inbred Strains ; }, abstract = {Mesotheliomas were induced in rats by the intrapleural injection of Western Australia crocidolite asbestos. Over a two-year period, 10 of 18 animals in which implants were established developed mesotheliomas, for a 56% success rate. Histologically, most mesotheliomas were biphasic although predominantly spindle celled. Pleural fluid was examined in five of these malignant cases: three had a papillary epithelial picture, one had mainly anaplastic cells, and one contained predominantly spindle-shaped cells. Three types of cell aggregates occurred: classical collagen-containing papillary clusters, spindle-cell aggregates and cystlike spheres. These last structures corresponded to microcystic or adenomatoid growth present in four mesotheliomas. Two of the effusions were cultured successfully; the growth pattern was typically mesothelial, with in vitro production of collagen. Ultrastructurally, long, slender microvilli, cell junctions and intermediate filaments confirmed the mesothelial nature of these asbestos-induced rat malignancies.}, } @article {pmid6424168, year = {1984}, author = {Holstein, EC and Deuschle, KW and Bosch, S and Fischer, E and Rohl, AN and Selikoff, IJ}, title = {Port Allegany Asbestos Health Program: a community response to a public health problem.}, journal = {Public health reports (Washington, D.C. : 1974)}, volume = {99}, number = {2}, pages = {193-199}, pmid = {6424168}, issn = {0033-3549}, mesh = {Asbestos/*adverse effects ; Community Health Services/*organization & administration ; Environmental Exposure ; Goals ; Health Promotion/methods/*organization & administration ; Humans ; Pennsylvania ; Public Health ; }, abstract = {The Port Allegany Asbestos Health Program (PAAHP) is a unique, community-run program that resulted from the successful cooperative efforts of a labor union, a corporation, community health care providers, and a medical school. PAAHP's goal is to develop a permanent community health organization that will use the most advanced existing knowledge to mitigate the adverse health effects anticipated as a result of the use of amosite asbestos in a Port Allegany, Pa. factory. All 1,188 persons employed by the factory during the years 1964-72 and the 3,000-4,000 persons in household contact with them are eligible for the program. PAAHP's major services are intensive medical surveillance, smoking cessation assistance, health education for participants, and continuing education for area physicians about asbestos-related diseases. One of the program's policies is not to disturb the usual patterns of medical care. If further testing or treatment is needed, patients are referred to their usual personal physicians. PAAHP does not provide ordinary medical care or medical insurance. Across the nation, the number of workers estimated to have been exposed to asbestos is more than 20 million, and their household contacts are estimated to be about three to four times that number. Adverse health effects resulting from asbestos exposure include elevated risk of lung cancer, mesothelioma, gastrointestinal tumors, and asbestosis. The problem requires the development of public health solutions. PAAHP has demonstrated the feasibility of a community-based model as one useful approach.}, } @article {pmid6692252, year = {1984}, author = {Vogelzang, NJ and Schultz, SM and Iannucci, AM and Kennedy, BJ}, title = {Malignant mesothelioma. The University of Minnesota experience.}, journal = {Cancer}, volume = {53}, number = {3}, pages = {377-383}, doi = {10.1002/1097-0142(19840201)53:3<377::aid-cncr2820530302>3.0.co;2-b}, pmid = {6692252}, issn = {0008-543X}, support = {CA-19527/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Doxorubicin/therapeutic use ; Female ; Humans ; Male ; Mesothelioma/*epidemiology/etiology/therapy ; Middle Aged ; Minnesota ; *Pericardium ; Peritoneal Neoplasms/*epidemiology/etiology/therapy ; Pleural Neoplasms/*epidemiology/etiology/therapy ; Prognosis ; Smoking ; }, abstract = {Between 1950 and 1981, 31 patients with mesothelioma were treated at the University of Minnesota. An average of 0.2 to 0.6 patients were seen per year between 1950 and 1970, and since 1970 there has been an average of 1.4 to 2.4 patients per year. Twenty-seven of the 28 patients with malignant mesothelioma are known or presumed dead. Mesotheliomas occurred in all areas of Minnesota, and 28.6% of the patients had a definite history of asbestos exposure. This was also a probable cause of the disease in an additional 25% of patients. The clinical findings and course of the disease were similar to other series. The median survival of all patients was eight months. Doxorubicin-treated patients survived a median of 16 months (range, 2-36 months). Malignant mesothelioma is being increasingly recognized in Minnesota and has a grim prognosis in spite of doxorubicin therapy.}, } @article {pmid6691935, year = {1984}, author = {Wright, WE and Sherwin, RP and Dickson, EA and Bernstein, L and Fromm, JB and Henderson, BE}, title = {Malignant mesothelioma: incidence, asbestos exposure, and reclassification of histopathology.}, journal = {British journal of industrial medicine}, volume = {41}, number = {1}, pages = {39-45}, pmid = {6691935}, issn = {0007-1072}, support = {P0-1 CA17054/CA/NCI NIH HHS/United States ; }, mesh = {Asbestos/*adverse effects ; California ; Diagnostic Errors ; Female ; Humans ; Male ; Mesothelioma/epidemiology/etiology/*pathology ; Occupational Diseases/epidemiology/etiology/*pathology ; Peritoneal Neoplasms/epidemiology/etiology/*pathology ; Pleural Neoplasms/epidemiology/etiology/*pathology ; Time Factors ; }, abstract = {The Los Angeles County Cancer Surveillance Program abstracts records on almost all cases of cancer occurring in the county. In a study of those cases of pleural and peritoneal malignant mesothelioma (MM) that occurred from 1972 to 1979 occupational histories were obtained during interviews, and histopathology of the tumours was reviewed and classified by a member of a mesothelioma reference panel who was unaware of the exposure histories. About half the cases reviewed had likely exposure to asbestos at work. The greatest proportion of cases designated as MM by the pathologist occurred among individuals likely to have had the heaviest exposure of asbestos (42%). No upward trend of incidence over time was apparent among cases designated as MM. The age adjusted incidence rates for designated MM were lower than in other studies. The well recognised interobserver variability in diagnosing MM apparently produces raised estimates of incidence and an overestimate of trends of incidence. The interobserver variability may result from different awareness of MM occurrence, a lack of precise histopathological criteria for the diagnosis, or the influence of a history of exposure to asbestos on the interpretation. A history of exposure to asbestos may bias interpretation of histopathology and should not be used to make the histological diagnosis.}, } @article {pmid6368466, year = {1984}, author = {Richter, ED}, title = {Asbestos exposure in Israel: findings, issues and needs.}, journal = {Israel journal of medical sciences}, volume = {20}, number = {2}, pages = {89-97}, pmid = {6368466}, issn = {0021-2180}, mesh = {Asbestos/*poisoning ; Asbestosis/*etiology/physiopathology ; Environmental Exposure ; Female ; *Health Services Needs and Demand ; *Health Services Research ; Humans ; Israel ; Lung Neoplasms/*etiology/physiopathology ; Male ; Maximum Allowable Concentration ; Mesothelioma/*etiology/physiopathology ; }, abstract = {In Israel, since the 1950s, at least several thousand workers, their wives and children, and possibly many others, have been or still may be exposed to hazardous amounts of airborne asbestos fibers. These are found both in asbestos-based industries (asbestos cement, textiles and brake linings) and trades with asbestos exposure (construction, shipyard repair, boiler maintenance, insulation work). These people are at increased risk for disability or illness, or for premature death from asbestosis, from lung cancer, from exacerbation of preexisting respiratory disease (especially if they smoke), from mesothelioma, from gastrointestinal cancer, and from other malignancies. Although there has been progress, much still has to be done in the areas of legislation, standard setting, exposure control, technology, surveillance, smoking cessation, and medical care and follow-up. Compensation is needed to care for those workers currently or previously exposed, as well as for their families and others at risk. A national policy for protecting and caring for those formerly or currently exposed is indicated by the review of the situation in Israel.}, } @article {pmid6723346, year = {1984}, author = {Wechsler, RJ and Rao, VM and Steiner, RM}, title = {The radiology of thoracic malignant mesothelioma.}, journal = {Critical reviews in diagnostic imaging}, volume = {20}, number = {4}, pages = {283-310}, pmid = {6723346}, issn = {1040-8371}, mesh = {Asbestosis/complications ; Humans ; Mesothelioma/diagnosis/*diagnostic imaging/epidemiology/etiology/pathology/therapy ; Pleural Effusion ; Pleural Neoplasms/diagnosis/*diagnostic imaging/epidemiology/etiology/pathology/therapy ; Tomography, X-Ray Computed ; United States ; }, abstract = {Formerly considered to be rare, primary malignant mesothelioma of the pleura has become a frequently diagnosed tumor during the last 30 years because of a more specific diagnostic criteria and because of its relationship with asbestos exposure. The radiologic findings associated with malignant mesothelioma of the pleura are not patho- neumonic but are characteristic and include a unilateral pleural effusion, unilateral pleural thickening, rib destruction and infra diaphragmatic spread, pulmonary nodules and masses and in distant metastases. These findings are in addition to the associated changes related to asbestos exposure. A review of the clinical records and radiographs of 26 patients with proven malignant mesothelioma studied at our institution serves as the basis for this review. The differential diagnosis radiologic findings and the relationship between these changes and the pathology clinical picture and the prognosis in this important disease entity is discussed.}, } @article {pmid6719076, year = {1984}, author = {Pillgram-Larsen, J and Urdal, L and Smith-Meyer, R and Birkeland, S}, title = {Malignant pleural mesothelioma. A clinical review of 19 patients.}, journal = {Scandinavian journal of thoracic and cardiovascular surgery}, volume = {18}, number = {1}, pages = {69-73}, doi = {10.3109/14017438409099387}, pmid = {6719076}, issn = {0036-5580}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Combined Modality Therapy ; Female ; Humans ; Male ; *Mesothelioma/diagnosis/etiology/therapy ; Middle Aged ; *Pleural Neoplasms/diagnosis/etiology/therapy ; Retrospective Studies ; }, abstract = {A retrospective study is presented of 19 patients with pleural mesothelioma diagnosed over an 18-year period (1964-1981). Two patients are alive after observation for 12 and 16 months. In 16 fatal cases the post-diagnosis survival time was 1-113 (median 17) months. One patient was lost to follow-up after 6 months. The male: female ratio was 5.3:1. The disease was most commonly detected in persons in their sixties and seventies. Pain and dyspnoea, the most common of the presenting symptoms, occurred in half of the patients. Weight loss and malaise were reported by six patients. Mesothelioma was most common on the right side, but often spread to the left, infiltrating the pericardium and the diaphragm. Metastases to abdominal organs were found in five of the eight autopsies, and in three other patients there were clinical signs of abdominal spread. Thoracotomy was performed in 12 patients, in one of whom radical removal of the tumor was attempted, but the patient died of recurrent tumor. Radiotherapy and cytostatic medication had no demonstrable effect on survival. Pleural effusion developed in all cases and all had roentgenologically demonstrated changes. Exposure to asbestos was documented in 6 of the 19 cases. In three asymptomatic patients the mesothelioma was incidentally revealed by routine X-ray examination, and these patients had significantly longer survival than the others. One of these tumors, however, had a relatively benign histologic appearance. Frequent X-ray examination of risk groups seems to offer the only prospect of improving management by earlier diagnosis.}, } @article {pmid6714106, year = {1984}, author = {Huuskonen, MS and Järvisalo, J and Koskinen, H and Nickels, J and Pasanen, J and Tossavainen, A}, title = {[Fiber minerals causing disease].}, journal = {Duodecim; laaketieteellinen aikakauskirja}, volume = {100}, number = {4}, pages = {197-205}, pmid = {6714106}, issn = {0012-7183}, mesh = {Asbestos/*adverse effects ; Asbestosis/etiology ; Finland ; Humans ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Occupational Diseases/*etiology ; }, } @article {pmid6488216, year = {1984}, author = {Fischbein, A and Sharma, OK and Solomon, S and Buschman, F and Apell, G and Kohn, M and Selikoff, IJ and Bekesi, JG and Borek, E}, title = {Transfer RNA breakdown products in the urine of asbestos workers.}, journal = {Cancer detection and prevention}, volume = {7}, number = {4}, pages = {247-252}, pmid = {6488216}, issn = {0361-090X}, mesh = {Adult ; Aged ; Asbestos/*toxicity ; Humans ; Male ; Mesothelioma/etiology ; Middle Aged ; Occupational Diseases/*etiology ; Pneumoconiosis/urine ; RNA, Transfer/*urine ; Reference Values ; Ribonucleosides/*urine ; Risk ; }, abstract = {Patients with malignant mesothelioma, a neoplasia strongly associated with previous asbestos exposure, excrete in the urine high levels of modified purines, pyrimidines, and their ribosides, breakdown products of transfer RNA. The urinary excretion levels of modified nucleosides were measured in 47 male insulation workers with long term exposure to asbestos and, therefore, at high neoplastic risk. The nucleoside levels of 44 male control subjects were used for comparison. Asbestos-related radiographic changes were found in 70% of the exposed individuals. An increasing severity of radiographic alterations was associated with a greater frequency of elevated nucleoside clusters, especially in m'A, m'I, m'G, and m2(2)G. Duration since onset of exposure was directly related to pseudouridine, m'I, and m2(2)G. Though cigarette smoking contributes to the development of asbestos-related lung cancer, data are presented that support the hypothesis that asbestos exposure is the more important factor related to the elevated values of nucleosides. It was concluded, therefore, that measuring nucleoside levels in populations at high risk of developing certain kinds of cancer may provide a useful diagnostic tool for detecting "preclinical" biochemical changes that may be predictive of future neoplastic manifestations.}, } @article {pmid6485695, year = {1984}, author = {Chachati, A and Hoyoux, P and Smoliar, V}, title = {Peritoneal mesothelioma: case report and review of the literature.}, journal = {Acta clinica Belgica}, volume = {39}, number = {3}, pages = {141-147}, doi = {10.1080/22953337.1984.11718998}, pmid = {6485695}, issn = {1784-3286}, mesh = {Aged ; Asbestos/adverse effects ; Humans ; Lung Neoplasms/secondary ; Male ; Mesothelioma/etiology/*pathology/secondary ; Peritoneal Neoplasms/etiology/*pathology ; }, } @article {pmid6484259, year = {1984}, author = {Le Gales, C}, title = {[Model for evaluation of occupational mortality related to asbestos (the case of the asbestos industry in France between 1950 and 1980)].}, journal = {Revue d'epidemiologie et de sante publique}, volume = {32}, number = {2}, pages = {122-133}, pmid = {6484259}, issn = {0398-7620}, mesh = {Adolescent ; Adult ; Age Factors ; Asbestosis/*mortality ; *Epidemiologic Methods ; France ; Humans ; Lung Neoplasms/*mortality ; Mathematics ; Mesothelioma/*mortality ; Middle Aged ; Models, Theoretical ; Occupations ; Risk ; Socioeconomic Factors ; }, abstract = {This article presents an evaluation model of the mortality attributed to asbestos occupational exposure. French workers exposed at least ten years between 1950 and 1979 constitute the population studied. Exposure-risk relations are used to estimate mortality from lung cancer, mesothelioma, or asbestosis, and the associated reduction of life expectancy among 76 groups (about 18,500 workers) defined by their level of asbestos exposure. The most important results are presented and discussed as are the main hypotheses regarding historical exposure parameters.}, } @article {pmid6484258, year = {1984}, author = {Le Gales, C and Oudiz, A}, title = {[Methodologic contribution to determining maximum occupational exposure levels for asbestos. Exposure-risk relation and economic criteria].}, journal = {Revue d'epidemiologie et de sante publique}, volume = {32}, number = {2}, pages = {113-121}, pmid = {6484258}, issn = {0398-7620}, mesh = {*Asbestos/adverse effects ; Asbestosis/economics/mortality/*prevention & control ; Female ; Humans ; Male ; Maximum Allowable Concentration ; Mesothelioma/etiology/mortality ; Socioeconomic Factors ; }, abstract = {It is not easy to set exposure limits for industrial carcinogens when only biological and epidemiological criteria are used. Hence, criteria should also include relevant social and economical considerations. This paper, using asbestos exposure as an example, explains how the economic aspects of prevention may be taken into account. The methodology includes three stages: use of the exposure-risk models in order to estimate the residual health effects associated with asbestos, according to various exposure limits, evaluation of costs of preventive measures required by these exposure limits, discussion of the exposure limits--a synthesis of the two preceding stages.}, } @article {pmid6463348, year = {1984}, author = {Taillandier, J and Faux, N and Manigand, G and Lemaigre, G and Zilhardt, P and Jagueux, M}, title = {[Diffuse bone metastases revealing pleural mesothelioma. Case report].}, journal = {Revue des maladies respiratoires}, volume = {1}, number = {1}, pages = {37-41}, pmid = {6463348}, issn = {0761-8425}, mesh = {Aged ; Asbestos ; Bone Neoplasms/*secondary ; Environmental Exposure ; Humans ; Male ; Mesothelioma/*pathology ; Pleural Neoplasms/*pathology ; Spinal Neoplasms/secondary ; }, abstract = {A 76 year old man, presenting with symptoms of general malaise alone, had a marrow biopsy which showed and undifferentiated carcinoma. A subsequent autopsy revealed a multi-nodular pleural mesothelioma, which was not seen radiologically, presumably because of the small size of the nodule. There were bilateral adrenal metastases and diffuse bony metastases involving the marrow. An occupational contact with asbestos was retrospectively confirmed. It is rare that a pleural mesothelioma does not exhibit thoracic signs and very uncommon that bony metastases should give the diagnosis in such a tumour.}, } @article {pmid6420020, year = {1984}, author = {Selikoff, IJ and Churg, J and Hammond, EC}, title = {Classics in Oncology: Asbestos exposure and neoplasia.}, journal = {CA: a cancer journal for clinicians}, volume = {34}, number = {1}, pages = {48-56}, doi = {10.3322/canjclin.34.1.48}, pmid = {6420020}, issn = {0007-9235}, mesh = {Adult ; Aged ; Asbestos/*adverse effects/history ; Epidemiologic Methods ; History, 20th Century ; Humans ; Male ; Middle Aged ; Respiratory Tract Neoplasms/*epidemiology/etiology/mortality ; Risk ; Time Factors ; United States ; }, abstract = {Building trades insulation workers have relatively light, intermittent exposure to asbestos. Of 632 insulation workers, who entered the trade before 1943 and were traced through 1962, 45 died of cancer of the lung or pleura, whereas only 6.6 such deaths were expected. Three of the pleural tumors were mesotheliomas; there was also one peritoneal mesothelioma. Four mesotheliomas in a total of 255 deaths is an exceedingly high incidence for such a rare tumor. In addition, an unexpectedly large number of men died of cancer of the stomach, colon, or rectum (29 compared with 9.4 expected). Other cancers were not increased; 20.5 were expected, and 21 occurred. Twelve men died of asbestosis.}, } @article {pmid6378527, year = {1984}, author = {Gefter, WB and Epstein, DM and Miller, WT}, title = {Radiographic evaluation of asbestos-related chest disorders.}, journal = {Critical reviews in diagnostic imaging}, volume = {21}, number = {2}, pages = {133-181}, pmid = {6378527}, issn = {1040-8371}, mesh = {Asbestos/*adverse effects ; Asbestosis/diagnostic imaging ; Carcinoma, Bronchogenic/diagnostic imaging/etiology ; Esophageal Neoplasms/diagnostic imaging/etiology ; Humans ; Lung Neoplasms/diagnostic imaging/etiology ; Mesothelioma/diagnostic imaging/etiology ; Occupational Diseases/*diagnostic imaging/etiology ; Pleural Diseases/*diagnostic imaging/etiology ; Pleural Effusion ; Pleural Neoplasms/diagnostic imaging/etiology ; Pulmonary Atelectasis/diagnostic imaging/etiology ; *Radiography, Thoracic ; }, abstract = {This paper reviews the radiographic, clinical, pathologic, and epidemiological features of pleural and pulmonary parenchymal disorders which have been related to asbestos exposure. In particular, the following are discussed: (1) pleural plaques--radiographic detection by plain films and computed tomography, normal and abnormal densities which may mimic plaques, the 1980 ILO U/C classification, recent epidemiological data on plaques including their relationship to carcinoma and mesothelioma; (2) diffuse pleural thickening; (3) benign asbestos pleural effusions; (4) mesothelioma--emphasizing recent advances in diagnosis, staging, therapy, and prognosis; (5) parenchymal fibrosis--pathogenesis, relationship to fiber exposure, plaques, and carcinoma; (6) bronchogenic carcinoma; (7) rounded atelectasis--recent observations on its association with pleural thickening. A role of radiology in medicolegal aspects of asbestos-related disease is briefly examined.}, } @article {pmid6326648, year = {1984}, author = {Rogers, AJ}, title = {Determination of mineral fibre in human lung tissue by light microscopy and transmission electron microscopy.}, journal = {The Annals of occupational hygiene}, volume = {28}, number = {1}, pages = {1-12}, doi = {10.1093/annhyg/28.1.1}, pmid = {6326648}, issn = {0003-4878}, mesh = {Adult ; Aged ; Asbestos/*analysis ; Asbestos, Amosite ; Asbestos, Crocidolite ; Asbestos, Serpentine ; Australia ; Humans ; Lung/*analysis ; Lung Neoplasms/analysis ; Male ; Mesothelioma/analysis ; Microscopy, Electron ; Middle Aged ; }, } @article {pmid6326567, year = {1984}, author = {Scansetti, G and Mollo, F and Tiberi, G and Andrion, A and Piolatto, G}, title = {Pleural mesothelioma after a short interval from first exposure in the wine filter industry.}, journal = {American journal of industrial medicine}, volume = {5}, number = {4}, pages = {335-339}, doi = {10.1002/ajim.4700050410}, pmid = {6326567}, issn = {0271-3586}, mesh = {Asbestos/*adverse effects ; Asbestos, Serpentine ; Humans ; Male ; Mesothelioma/*etiology ; Middle Aged ; Occupational Diseases/*etiology ; Pleural Neoplasms/*etiology ; *Wine ; }, abstract = {Pleural mesotheliomas are usually reported after a long interval has passed since first exposure to asbestos. We, however, describe a case observed after a latent period of only 7.5 years in a worker exposed in a factory manufacturing auxiliary products for wine treatment, including chrysotile asbestos filters. The exposure to asbestos lasted 3-4 months per year, during which airborne fiber concentrations ranged from 1 to 4 ff/cc in the patient's workplace. Due to the characteristics of the manufacturing process, the asbestos fibers were very thin in diameter. The patient also suffered from nasal breathing impairment. An examination of the literature showed that asbestos-related mesotheliomas have been reported, albeit rarely, after less than 10 years from onset of exposure. Therefore, it is believed that this case should be related to past exposure to asbestos.}, } @article {pmid6321301, year = {1984}, author = {Kolev, K and Topov, Ia}, title = {[Morphological characteristics of experimental peritoneal and pleural mesotheliomas caused by crocidolite asbestos].}, journal = {Gigiena truda i professional'nye zabolevaniia}, volume = {}, number = {1}, pages = {31-34}, pmid = {6321301}, issn = {0016-9919}, mesh = {Animals ; Asbestos/*adverse effects ; Asbestos, Crocidolite ; Female ; Mesothelioma/*etiology/pathology ; Peritoneal Neoplasms/*etiology/pathology ; Pleural Neoplasms/*etiology/pathology ; Rats ; Rats, Inbred Strains ; }, } @article {pmid6239041, year = {1984}, author = {Rosenstock, L}, title = {Occupational cancer: clinical interpretation and application of scientific evidence.}, journal = {Journal of toxicology. Clinical toxicology}, volume = {22}, number = {3}, pages = {261-282}, doi = {10.3109/15563658408992559}, pmid = {6239041}, issn = {0731-3810}, mesh = {Aged ; Air Pollutants, Occupational/adverse effects ; Asbestos/adverse effects ; Benzene/poisoning ; Epidemiologic Methods ; Humans ; Leukemia, Myeloid, Acute/chemically induced ; Lung Neoplasms/etiology ; Male ; Mesothelioma/etiology ; Middle Aged ; Neoplasms/*etiology ; Occupational Diseases/*etiology ; *Occupations ; *Smoking ; Workers' Compensation ; }, abstract = {Maintaining an awareness that workplace factors may contribute to occupational cancer is one of the most formidable obstacles in early clinical recognition. This early recognition provides an opportunity for a practicing physician to make an important contribution to new knowledge in the field. Another important reason for the physician to have a high index of suspicion of cancers being related to workplace exposures has to do with compensation benefits which may accrue to the injured worker. The physician's role in the compensation system is critical both in providing medical opinion, which is material to the final decision, and because in many states it is the physician who starts the time clock for the statute of limitations. Three case examples are used to illustrate the importance of clinical recognition by an alert physician: 1) mesothelioma and labor; 2) lung cancer in a plumber who smokes and one who does not smoke; 3) leukemia in a rubber industry worker. Given the inherent preventable nature of occupational cancers, it is hoped that society will assist in searching for these important links.}, } @article {pmid6231722, year = {1984}, author = {Mowé, G and Gylseth, B}, title = {Medico-legal aspects of malignant mesothelioma.}, journal = {Scandinavian journal of social medicine}, volume = {12}, number = {1}, pages = {15-23}, doi = {10.1177/140349488401200104}, pmid = {6231722}, issn = {0300-8037}, mesh = {Aged ; Asbestos/*adverse effects/analysis ; Female ; Humans ; Lung Neoplasms/analysis/etiology ; Male ; Mesothelioma/analysis/*etiology ; Norway ; Occupational Diseases/*etiology ; Social Security/*legislation & jurisprudence ; Time Factors ; Workers' Compensation/legislation & jurisprudence ; }, abstract = {The object of this investigation was to discuss medico-legal aspects of malignant mesothelioma in relation to social insurance legislation for occupational injuries and diseases in Norway. During the period 1960-79 the Cancer Registry of Norway recorded a total of 155 men and 35 women with malignant mesothelioma. However, only 21 men and no women were notified to the National Insurance Institution as occupational disease cases before 31 December 1979, in spite of the well established causal association between occupational asbestos exposure and the disease. The investigation is based on these 21 patients. The long latency period from first asbestos exposure until appearance of the disease and the short survival were evident in this study. Furthermore, the legislation and provisions for occupational injuries and diseases in Norway are obviously intended for occupational accidents, and consequently the legal assessment of patients with malignant mesothelioma was complicated. For those notified, the delay in notification was considerable, and only 50% were notified before death. Delay in the claim procedure was also substantial, and few patients survived the claim procedure period. The decisions were not consistent, particularly decisions regarding "the year of injury" and appeared to have been more restrictive during recent years. One of the 21 cases was not accepted as occupational disease, because domestic exposure was considered more probable than occupational exposure.}, } @article {pmid6230471, year = {1984}, author = {Naka, H and Naka, A}, title = {[Clinicopathological study on 100 Japanese patients with peritoneal mesothelioma in Japan].}, journal = {Gan no rinsho. Japan journal of cancer clinics}, volume = {30}, number = {1}, pages = {1-10}, pmid = {6230471}, issn = {0021-4949}, mesh = {Adult ; Age Factors ; Aged ; Female ; Humans ; Japan ; Laparoscopy ; Lymphatic Metastasis ; Male ; Mesothelioma/diagnosis/epidemiology/*pathology ; Middle Aged ; Neoplasm Metastasis ; Peritoneal Neoplasms/diagnosis/epidemiology/*pathology ; Prognosis ; Sex Factors ; }, abstract = {We report a clinicopathological study on 100 japanese patients with peritoneal mesothelioma encountered between 1911 and 1982. Fifty-six were males and 44 were females, they ranged in age from 10 months to 83 years. As the inducement materials, asbestos was reported in 5 and thorium in 2 patients. Clinical symptoms were abdominal distension in 56 and abdominal pain in 50 patients. Thrombocytosis and hypoglycemia were observed in 7 and 3 patients, respectively. Macroscopically, the peritoneal mesothelioma was localized in 7, diffuse in 86 and not described in 7 patients. The pathological classification was benign in 5 and malignant in 77 cases. According to Stout's classification, the peritoneal mesothelioma was tubular in 43 mixed in 25 and fibrous type in 11 cases. Based on our findings we suggest that peritoneal mesotheliomas are on the increase in Japan.}, } @article {pmid6140594, year = {1983}, author = {Steineck, G and Carstensen, J and Wiklund, K and Eklund, G}, title = {Mesothelioma among sugar refinery workers.}, journal = {Lancet (London, England)}, volume = {2}, number = {8365-66}, pages = {1503}, doi = {10.1016/s0140-6736(83)90851-6}, pmid = {6140594}, issn = {0140-6736}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Carbohydrates ; Humans ; Male ; Mesothelioma/*etiology ; Middle Aged ; *Occupational Diseases ; Pleural Neoplasms/*etiology ; }, } @article {pmid6140525, year = {1983}, author = {Clarke, GD and Newman, RH and O'Neill, CH and Parry, DW}, title = {Exposure to asbestos versus organic fibrous dusts.}, journal = {Lancet (London, England)}, volume = {2}, number = {8364}, pages = {1423-1424}, doi = {10.1016/s0140-6736(83)90957-1}, pmid = {6140525}, issn = {0140-6736}, mesh = {Asbestos/*adverse effects ; Dust/*adverse effects ; Environmental Exposure ; Humans ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; *Plants, Edible ; }, } @article {pmid6228860, year = {1983}, author = {Vacherot, B and Rossert, J and Conso, F and Fouret, P and Touboul, J}, title = {[Myeloproliferative syndrome followed by mesothelioma after exposure to asbestos].}, journal = {Presse medicale (Paris, France : 1983)}, volume = {12}, number = {44}, pages = {2824}, pmid = {6228860}, issn = {0755-4982}, mesh = {Aged ; Asbestos/*adverse effects ; Humans ; Male ; Mesothelioma/*etiology ; Myeloproliferative Disorders/*etiology ; Pleural Neoplasms/*etiology ; }, } @article {pmid6671533, year = {1983}, author = {Kolev, K}, title = {[Hygienic significance of submicroscopic fractions of asbestos dust in occupational and domestic environments].}, journal = {Gigiena i sanitariia}, volume = {}, number = {12}, pages = {50-51}, pmid = {6671533}, issn = {0016-9900}, mesh = {Air Pollutants/*adverse effects ; Air Pollutants, Occupational/*adverse effects ; Animals ; *Asbestos ; Mesothelioma/etiology ; Neoplasms/etiology ; Occupational Diseases/*etiology ; Particle Size ; Rats ; Rats, Inbred Strains ; }, } @article {pmid6668297, year = {1983}, author = {Nichols, DM and Johnson, MA}, title = {Calcification in a pleural mesothelioma.}, journal = {Journal of the Canadian Association of Radiologists}, volume = {34}, number = {4}, pages = {311-313}, pmid = {6668297}, issn = {0008-2902}, mesh = {Asbestosis/complications ; Calcinosis/*diagnostic imaging/etiology ; Humans ; Kidney Failure, Chronic/complications ; Male ; Mesothelioma/complications/*diagnostic imaging ; Middle Aged ; Pleural Neoplasms/complications/*diagnostic imaging ; Tomography, X-Ray Computed ; }, abstract = {Extensive calcification in a rapidly growing malignant mixed mesothelioma of the pleura was observed on plain radiography and computed tomography of the chest in a patient with a long history of asbestos exposure and chronic renal failure.}, } @article {pmid6641667, year = {1983}, author = {Glickman, LT and Domanski, LM and Maguire, TG and Dubielzig, RR and Churg, A}, title = {Mesothelioma in pet dogs associated with exposure of their owners to asbestos.}, journal = {Environmental research}, volume = {32}, number = {2}, pages = {305-313}, doi = {10.1016/0013-9351(83)90114-7}, pmid = {6641667}, issn = {0013-9351}, support = {RR05464/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; *Animals, Domestic ; Asbestos/*adverse effects ; Dog Diseases/*etiology ; Dogs ; Environmental Exposure ; Female ; Humans ; Male ; Mesothelioma/diagnosis/etiology/*veterinary ; Occupations ; Risk ; }, abstract = {Pet dogs with spontaneous mesothelioma were used to identify environmental exposures that might increase their owner's risk of asbestos-related disease. These animals share man's domicile environment, yet do not indulge in activities (e.g., smoking, working) which confound interpretation of epidemiologic studies. Eighteen histologically confirmed canine mesotheliomas were diagnosed at the Veterinary Hospital of the University of Pennsylvania, Philadelphia, from April 1977 to December 1981. Sixteen owners of cases and 32 owners of age, breed, and sex-matched controls were interviewed to determine their occupation and medical history and their dog's medical history, life style, diet, and exposure to asbestos. An asbestos-related occupation or hobby of a household member and use of flea repellents on the dog were significantly associated with mesothelioma. In addition, there was a trend indicating an increased risk of mesothelioma with an urban residence. Lung tissue from three dogs with mesothelioma and one dog with squamous cell carcinoma of the lung had higher levels of chrysotile asbestos fibers than lung tissue from control dogs. These findings indicate that well-designed epidemiological studies of spontaneous tumors in pet animals may provide insight into the role of environmental factors in human cancers and serve as a valuable sentinel model to identify environmental health hazards for humans.}, } @article {pmid6668488, year = {1983}, author = {Antman, KH and Corson, JM and Li, FP and Greenberger, J and Sytkowski, A and Henson, DE and Weinstein, L}, title = {Malignant mesothelioma following radiation exposure.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {1}, number = {11}, pages = {695-700}, doi = {10.1200/JCO.1983.1.11.695}, pmid = {6668488}, issn = {0732-183X}, mesh = {Adenocarcinoma/pathology/radiotherapy ; Adult ; Breast Neoplasms/pathology/radiotherapy ; Dysgerminoma/pathology/radiotherapy ; Female ; Fibrosarcoma/pathology/radiotherapy ; Humans ; Male ; Mesothelioma/*etiology/pathology ; Middle Aged ; Neoplasms, Radiation-Induced/*pathology ; Ovarian Neoplasms/pathology/radiotherapy ; Peritoneal Neoplasms/*etiology/pathology ; Pleural Neoplasms/*etiology/pathology ; Teratoma/pathology/radiotherapy ; Testicular Neoplasms/pathology/radiotherapy ; Time Factors ; }, abstract = {Mesothelioma developed in proximity to the field of therapeutic radiation administered 10-31 years previously in four patients. In three, mesothelioma arose within the site of prior therapeutic radiation for another cancer. Mesothelioma in the fourth patient developed adjacent to the site of cosmetic radiation to a thyroidectomy scar. None of these four patients recalled an asbestos exposure or had evidence of asbestosis on chest roentgenogram. Lung tissue in one patient was negative for ferruginous bodies, a finding considered to indicate no significant asbestos exposure. Five other patients with radiation-associated mesothelioma have been reported previously, suggesting that radiation is an uncommon cause of human mesothelioma. Problems in the diagnosis of radiation-associated mesotheliomas are considered.}, } @article {pmid6662096, year = {1983}, author = {Sigurdson, EE}, title = {Observations of cancer incidence surveillance in Duluth, Minnesota.}, journal = {Environmental health perspectives}, volume = {53}, number = {}, pages = {61-67}, pmid = {6662096}, issn = {0091-6765}, mesh = {Adult ; Asbestos/*adverse effects ; Female ; Humans ; Male ; Mesothelioma/epidemiology ; Minnesota ; Neoplasms/*epidemiology ; Population Surveillance ; Risk ; Time Factors ; *Water Supply ; }, abstract = {In 1973, amphibole asbestos fibers were discovered in the municipal water supply of Duluth, Minnesota. The entire city population of approximately 100,000 was exposed from the late 1950s through 1976 at levels of 1-65 million fibers per liter of water. Because of previous epidemiologic studies that linked mesothelioma, lung and gastrointestinal cancers to occupational exposure to asbestos, surveillance of cancer incidence in residents of Duluth was initiated to determine the health effect from ingestion of asbestos. The methodology of the Third National Cancer Survey (TNCS) and SEER Program was used. Duluth 1969-1971 rates were compared with TNCS rates for the cities of Minneapolis and St. Paul during 1969-1971; Duluth rates during 1974-1976 are compared with Duluth 1969-1971; Duluth rates during 1979-1980 are compared with Duluth 1969-1971 and with Iowa SEER; and a table of the occurrence of malignant mesothelioma is presented. Statistically significant excesses are observed in several primary sites in Duluth residents. However, lung cancer in Duluth females is the only primary site considered also of biological significance. The mesothelioma incidence rate is no more than expected. This paper also describes the problems of long-term surveillance of exposed populations considered at risk of environment cancer, the need for improved study methodologies and the use of federal records for follow up of exposed individuals.}, } @article {pmid6647189, year = {1983}, author = {Harrison, RN and Hibberd, SC and Dadds, JH}, title = {Malignant pleural mesothelioma at St Mary's Hospital, Portsmouth--a review of 29 fatal cases.}, journal = {Postgraduate medical journal}, volume = {59}, number = {697}, pages = {712-716}, pmid = {6647189}, issn = {0032-5473}, mesh = {Aged ; Asbestos/adverse effects ; Environmental Exposure ; Female ; Humans ; Male ; Mesothelioma/*etiology/pathology ; Middle Aged ; Pleural Neoplasms/*etiology/pathology ; Retrospective Studies ; }, abstract = {The clinical details are presented of 29 fatal cases of pleural mesothelioma in the majority of which there was a history of exposure to asbestos during dockyard work in Portsmouth. Chest pain, breathlessness and weight loss dominated the clinical picture. Analgesia and repeated pleural aspirations provided temporary relief but symptoms invariably progressed. The mean survival time was 39 weeks. Only one patient survived longer than 2 years from hospital presentation. At autopsy, extensive local spread was usual but a high proportion of patients also had metastases at distant sites.}, } @article {pmid6628014, year = {1983}, author = {Weill, H}, title = {Asbestos-associated diseases. Science, public policy, and litigation.}, journal = {Chest}, volume = {84}, number = {5}, pages = {601-608}, doi = {10.1378/chest.84.5.601}, pmid = {6628014}, issn = {0012-3692}, mesh = {Asbestos/*adverse effects ; Asbestosis/economics/prevention & control ; Humans ; Legislation as Topic ; Lung Neoplasms/economics/prevention & control ; Mesothelioma/economics/prevention & control ; Occupational Diseases/economics/*prevention & control ; Pleural Diseases/economics/prevention & control ; *Public Policy ; United States ; }, } @article {pmid6605761, year = {1983}, author = {Wagner, MM and Darke, C and Coles, RM and Evans, CC}, title = {HLA-A and B antigen frequencies and mesothelioma in relation to asbestos exposure.}, journal = {British journal of cancer}, volume = {48}, number = {5}, pages = {727-730}, pmid = {6605761}, issn = {0007-0920}, mesh = {Aged ; Asbestos/adverse effects ; Asbestosis/*immunology ; HLA Antigens/*analysis ; HLA-A Antigens ; HLA-A11 Antigen ; HLA-A2 Antigen ; HLA-B Antigens ; HLA-B8 Antigen ; Humans ; Male ; Mesothelioma/*immunology ; Occupational Diseases/*immunology ; Pleural Neoplasms/*immunology ; }, } @article {pmid6313034, year = {1983}, author = {Gylseth, B and Mowé, G and Wannag, A}, title = {Fibre type and concentration in the lungs of workers in an asbestos cement factory.}, journal = {British journal of industrial medicine}, volume = {40}, number = {4}, pages = {375-379}, pmid = {6313034}, issn = {0007-1072}, mesh = {Aged ; Asbestos/adverse effects/*analysis ; Asbestos, Amosite ; Asbestos, Amphibole ; Asbestos, Crocidolite ; Asbestos, Serpentine ; Carcinoma, Bronchogenic/etiology ; Humans ; Lung/*analysis ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Middle Aged ; Occupational Diseases/*etiology ; Pleural Neoplasms/etiology ; Silicon Dioxide/analysis ; }, abstract = {The predominant asbestos fibre type used in the production of asbestos cement is chrysotile. The use of asbestos in relation to fibre type in a Norwegian asbestos cement plant during 1942-80 was 91.7% chrysotile, 3.1% amosite, 4.1% crocidolite, and 1.1% anthophyllite respectively. Electron microscopy and x ray microanalysis of lung tissue samples of asbestos cement workers who had died of malignant pleural mesothelioma or bronchogenic carcinoma showed a completely inverse ratio with regard to fibre type. The percentage of chrysotile asbestos in lung tissue varied between 0% and 9% whereas the corresponding numbers for the amphiboles were 76% and 99%. These differences are discussed with respect to the behaviour of different fibre types in the human body and to the occurrence of malignant mesothelioma in this asbestos cement factory.}, } @article {pmid6313033, year = {1983}, author = {McDonald, AD and Fry, JS and Woolley, AJ and McDonald, JC}, title = {Dust exposure and mortality in an American factory using chrysotile, amosite, and crocidolite in mainly textile manufacture.}, journal = {British journal of industrial medicine}, volume = {40}, number = {4}, pages = {368-374}, pmid = {6313033}, issn = {0007-1072}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Asbestos, Amosite ; Asbestos, Crocidolite ; Asbestos, Serpentine ; Asbestosis/etiology/mortality ; Dust/adverse effects ; Humans ; Lung Neoplasms/etiology/mortality ; Male ; Mesothelioma/etiology/mortality ; Middle Aged ; Occupational Diseases/etiology/*mortality ; *Textile Industry ; }, abstract = {This report describes the second in a series of three parallel cohort studies of asbestos factories in South Carolina, Pennsylvania, and Connecticut to assess the effects of mineral fibre type and industrial process on mortality from malignant mesothelioma, respiratory cancer, and asbestosis. In the present plant (in Pennsylvania) mainly chrysotile, with some amosite and a small amount of crocidolite, were used primarily in textile manufacture. Of a cohort of 4137 men comprising all those employed 1938-59 for at least a month, 97% were traced. By the end of 1974, 1400 (35%) had died, 74 from asbestosis and 70 from lung cancer. Mesothelioma was mentioned on the certificate in 14 deaths mostly coded to other causes. All these deaths occurred after 1959, and there were indications that additional cases of mesothelioma may have gone unrecognised, especially before that date. The exposure for each man was estimated in terms of duration and dust concentration in millions of dust particles per cubic foot (mpcf) from available measurements. Analyses were made both by life table and case referent methods. The standardised mortality ratio for respiratory cancer for the whole cohort was 105.0, but the risk rose linearly from 66.9 for men with less than 10 mpcf.y to 416.1 for those with 80 mpcf.y or more. Lines fitted to relative risks derived from SMRs in this and the textile plant studied in South Carolina were almost identical in slope. This was confirmed by case referent analysis. These findings support the conclusion from the South Carolina study that the risk of lung cancer in textile processing is very much greater than in chrysotile production and probably than in the friction products industry. The much greater risk of mesothelioma from exposure to processes in which even quite small quantities of amphiboles were used was also confirmed.}, } @article {pmid6313032, year = {1983}, author = {McDonald, AD and Fry, JS and Woolley, AJ and McDonald, J}, title = {Dust exposure and mortality in an American chrysotile textile plant.}, journal = {British journal of industrial medicine}, volume = {40}, number = {4}, pages = {361-367}, pmid = {6313032}, issn = {0007-1072}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Asbestos, Serpentine ; Asbestosis/etiology/mortality ; Dust/adverse effects ; Humans ; Lung Neoplasms/etiology/mortality ; Male ; Mesothelioma/etiology/mortality ; Middle Aged ; Occupational Diseases/etiology/*mortality ; *Textile Industry ; Time Factors ; }, abstract = {Three parallel cohort studies of asbestos factory workers were undertaken to investigate the effects of mineral fibre type and industrial process on malignant mesothelioma, respiratory cancer, and asbestosis. This report describes the mortality of a cohort of 2543 men, defined as all those employed for at least a month from 1938 to 1958 in a textile plant in South Carolina in which chrysotile was the only type of asbestos used. Of these, 863 men (34%) had died before 31 December 1977, one from malignant mesothelioma. Twenty one deaths were ascribed to asbestosis and 66 to cancer of the lung. Compared with the number expected from South Carolina, there was an excess of 30 deaths from respiratory cancer (ICD 160-164) in men 20 or more years after first employment (SMR 199.5). In men employed five years or more, no SMRs for this category rose above 300. Individual exposures were estimated (in mpcf X years) from recorded environmental measurements. Life table analyses and "log-rank" (case-control) analyses both showed a steep linear exposure-response that was some 50-fold greater at similar accumulated dust exposures than in Canadian chrysotile mining and milling. These findings agree closely with those from another study in this plant and confirm that mesothelioma is rarely associated with chrysotile exposure. Cigarette smoking habits did not greatly differ between the textile workers and the Canadian miners and millers. The far greater risk of lung cancer in the textile industry, if not attributable to other identified cocarcinogens, may be related to major differences in the size distribution of fibres in the submicroscopic range which are not detected by the usual fibre or particle counting procedures.}, } @article {pmid6648853, year = {1983}, author = {Law, MR and Ward, FG and Hodson, ME and Heard, BE}, title = {Evidence for longer survival of patients with pleural mesothelioma without asbestos exposure.}, journal = {Thorax}, volume = {38}, number = {10}, pages = {744-746}, pmid = {6648853}, issn = {0040-6376}, mesh = {Adult ; Aged ; Asbestos/*adverse effects/analysis ; Environmental Exposure ; Female ; Humans ; Lung/analysis ; Male ; Mesothelioma/etiology/*mortality ; Middle Aged ; Pleural Neoplasms/etiology/*mortality ; Time Factors ; }, abstract = {In a group of 23 patients with histologically confirmed malignant mesothelioma of the pleura who could not recall exposure to asbestos dust, survival was significantly longer than in a group of 83 patients with known exposure. Asbestos bodies were found by a quantitative method significantly less frequently in the unexposed than in the exposed group. The longer survival of patients without known exposure could not be correlated with any significant difference in the histological cell types of the tumours from those of exposed patients. In the 83 patients with known exposure survival did not relate to duration of exposure. Consequently, although the tumours of patients unable to recall exposure may be caused by unrecognised environmental contamination with asbestos dust, the longer survival of these patients would suggest a different aetiology.}, } @article {pmid6645416, year = {1983}, author = {Browne, K}, title = {The epidemiology of mesothelioma.}, journal = {The Journal of the Society of Occupational Medicine}, volume = {33}, number = {4}, pages = {190-194}, doi = {10.1093/occmed/33.4.190}, pmid = {6645416}, issn = {0301-0023}, mesh = {Adolescent ; Adult ; Asbestos/*adverse effects ; Child ; *Epidemiologic Methods ; Female ; Humans ; Male ; Mesothelioma/*etiology ; Middle Aged ; Risk ; }, } @article {pmid6631560, year = {1983}, author = {Teta, MJ and Lewinsohn, HC and Meigs, JW and Vidone, RA and Mowad, LZ and Flannery, JT}, title = {Mesothelioma in Connecticut, 1955-1977. Occupational and geographic associations.}, journal = {Journal of occupational medicine. : official publication of the Industrial Medical Association}, volume = {25}, number = {10}, pages = {749-756}, pmid = {6631560}, issn = {0096-1736}, support = {N01-CP-33235/CP/NCI NIH HHS/United States ; N01-CP-61002/CP/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Connecticut ; Female ; Humans ; Job Description ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Diseases/*epidemiology/etiology ; Peritoneal Neoplasms/epidemiology/etiology ; Pleural Neoplasms/*epidemiology/etiology ; Population Surveillance ; Risk ; }, abstract = {All cases of malignant mesothelioma (201) and other primary malignant pleural tumors (19) reported to the Connecticut Tumor Registry from 1955 through 1977 were studied in an attempt to identify high-risk jobs, industries and geographic locations and to estimate the risk attributable to asbestos exposure in the workplace. Data were obtained from hospital records, death certificates and city directories for cases, case spouses and a random sample (604) of Connecticut decedents (1955-1975). Three cases involved histories of work in asbestos products manufacture, but there was no evidence of residential risk in that geographic area. Relative risk (RR) for carpenters and cabinetmakers was 2.25 (p less than .05); for plumbers and pipefitters, 3.87 (p less than .05); and for persons "ever employed" in the rubber industry, 5.08 (p less than .01). Occupational exposure was indicated in 85% of the cases; attributable risk (AR) was 36%. Risk increased with greater exposure and older age. AR was 81% in men aged 70 to 89 years at diagnosis. Reduction of unnecessary occupational asbestos exposure remains the highest public health priority.}, } @article {pmid6631557, year = {1983}, author = {McMillan, GH}, title = {The health of welders in naval dockyards. The risk of asbestos-related diseases occurring in welders.}, journal = {Journal of occupational medicine. : official publication of the Industrial Medical Association}, volume = {25}, number = {10}, pages = {727-730}, doi = {10.1097/00043764-198310000-00011}, pmid = {6631557}, issn = {0096-1736}, mesh = {Asbestos/*adverse effects ; England ; Humans ; Male ; Mesothelioma/epidemiology/etiology ; *Naval Medicine ; Occupational Diseases/epidemiology/*etiology ; Pleural Diseases/epidemiology/etiology ; Pleural Neoplasms/epidemiology/etiology ; Pulmonary Fibrosis/diagnostic imaging/epidemiology/etiology ; Radiography, Thoracic ; Risk ; Smoking ; *Welding ; }, abstract = {Welders employed in Her Majesty's Dockyards before the late 1960s are likely to have been exposed to asbestos dust at work. Several studies have been made to assess the risk of their developing asbestos-related pulmonary parenchymal fibrosis, pleural fibrosis and mesothelioma. Potential exposures and their possible effects are described.}, } @article {pmid6622324, year = {1983}, author = {Varkey, B}, title = {Asbestos exposure. An update on pleuropulmonary hazards.}, journal = {Postgraduate medicine}, volume = {74}, number = {4}, pages = {93-9, 102-3}, doi = {10.1080/00325481.1983.11698456}, pmid = {6622324}, issn = {0032-5481}, mesh = {Aged ; Asbestos/*adverse effects ; Asbestosis/*etiology ; Carcinoma, Bronchogenic/etiology ; Humans ; Lung Diseases/*etiology ; Lung Neoplasms/etiology ; Male ; Mesothelioma/etiology ; Middle Aged ; Pleural Diseases/*etiology ; Pleural Neoplasms/etiology ; }, abstract = {Asbestos exposure is causally related to the development of asbestosis, bronchogenic carcinoma, malignant mesothelioma, and nonmalignant pleural disorders. Clinical and roentgenographic manifestations of asbestosis mimic other diffuse fibrotic lung diseases. However, a concomitant finding of pleural plaques strongly suggests the diagnosis. The manifestations of bronchogenic carcinoma related to asbestos exposure are varied and do not differ from those unrelated to asbestos exposure. Malignant mesothelioma signals previous asbestos exposure. Nonmalignant pleural disorders may not cause any symptoms but should alert the physician to other concurrent or potential asbestos-related diseases. To diagnose asbestos-related diseases, physicians should bear in mind the long latent period and should take a careful, comprehensive occupational and environmental history. Cigarette smoking markedly increases the risk for development of bronchogenic carcinoma in asbestos workers and increases the mortality due to asbestosis.}, } @article {pmid6614951, year = {1983}, author = {Ordóñez, NG and Smith, JL}, title = {Peritoneal malignant mesothelioma with multiple distant skin metastases.}, journal = {Archives of dermatology}, volume = {119}, number = {10}, pages = {827-830}, doi = {10.1001/archderm.1983.01650340037016}, pmid = {6614951}, issn = {0003-987X}, mesh = {Asbestos/adverse effects ; Humans ; Male ; *Mesothelioma/pathology ; Middle Aged ; *Peritoneal Neoplasms/pathology ; Skin Neoplasms/pathology/*secondary ; }, abstract = {Metastases in multiple distant sites, including the skin, developed in a 54-year-old man with diffuse malignant abdominal mesothelioma. To our knowledge, this represents the first reported case of cutaneous metastasis arising from malignant mesothelioma. Recent advances in diagnostic techniques, such as electron microscopy, may be helpful in differentiating this condition from metastatic adenocarcinoma.}, } @article {pmid6357260, year = {1983}, author = {Hillerdal, G}, title = {Malignant mesothelioma 1982: review of 4710 published cases.}, journal = {British journal of diseases of the chest}, volume = {77}, number = {4}, pages = {321-343}, pmid = {6357260}, issn = {0007-0971}, mesh = {Adolescent ; Adult ; Aged ; Asbestos/adverse effects ; Child ; Child, Preschool ; Female ; Heart Neoplasms/pathology ; Humans ; Infant ; Male ; Mesothelioma/diagnosis/etiology/*pathology ; Middle Aged ; Pericardium/pathology ; Peritoneal Neoplasms/pathology ; Pleural Neoplasms/pathology/therapy ; Prognosis ; Testicular Neoplasms/pathology ; }, } @article {pmid6352461, year = {1983}, author = {Greenberg, SD}, title = {Recent advances in pulmonary cytopathology.}, journal = {Human pathology}, volume = {14}, number = {10}, pages = {901-912}, doi = {10.1016/s0046-8177(83)80165-8}, pmid = {6352461}, issn = {0046-8177}, support = {CA-27313/CA/NCI NIH HHS/United States ; }, mesh = {Asbestos/adverse effects ; Biopsy, Needle ; Bronchoscopy ; Carcinoma, Bronchogenic/pathology ; Computers ; Female ; Humans ; Leukocytes/classification ; Lung Diseases/diagnosis/*pathology ; Lung Neoplasms/*pathology/secondary/surgery ; Macrophages/cytology ; Male ; Mesothelioma/pathology ; Metaplasia/pathology ; Middle Aged ; Pleural Effusion ; Pleural Neoplasms/diagnosis/etiology/pathology ; Pulmonary Alveoli/cytology ; Smoking ; Sputum/cytology ; }, abstract = {During the past five years, advances in pulmonary cytopathology have made possible the achievement of several goals, including the diagnosis of pneumonias in immunocompromised hosts, the detection and localization of occult lung cancers in high-risk cigarette smokers, the diagnosis of lesions of the lungs and chest wall by fine-needle aspiration, and the detection of asbestos exposure by sputum cytologic studies. Significant progress has also been made in the application of cell image analysis to the detection of premalignant bronchial epithelial cells in sputum. For the most part, these advances are based on such well-known cytologic procedures as the preparation of thin and evenly distributed smears, prompt fixation, properly controlled and monitored Papanicolaou staining, and thorough screening of slides. Such diligence in laboratory techniques remains the backbone of excellence in pulmonary cytopathology. Cytologic findings should be interpreted with the clinical features of each case in mind, for the practice of pulmonary cytopathology remains an art as well as a science.}, } @article {pmid6235434, year = {1983}, author = {Barnes, R}, title = {Compensable asbestos-related disease in New South Wales.}, journal = {The Medical journal of Australia}, volume = {2}, number = {5}, pages = {221-224}, doi = {10.5694/j.1326-5377.1983.tb122428.x}, pmid = {6235434}, issn = {0025-729X}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Asbestosis/diagnosis/mortality ; Australia ; Carcinoma, Bronchogenic/etiology/mortality ; Humans ; Lung Neoplasms/etiology/mortality ; Mesothelioma/etiology/mortality ; Middle Aged ; Occupational Diseases/*etiology/mortality ; Peritoneal Neoplasms/etiology/mortality ; Pleural Neoplasms/etiology/mortality ; Retrospective Studies ; Smoking ; *Workers' Compensation ; }, } @article {pmid6884101, year = {1983}, author = {Churg, A}, title = {Current issues in the pathologic and mineralogic diagnosis of asbestos-induced disease.}, journal = {Chest}, volume = {84}, number = {3}, pages = {275-280}, doi = {10.1378/chest.84.3.275}, pmid = {6884101}, issn = {0012-3692}, mesh = {Asbestos/analysis/classification ; Asbestosis/complications/*pathology ; Bronchi/analysis ; Environmental Exposure ; Humans ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Pleural Effusion/etiology ; }, } @article {pmid6651349, year = {1983}, author = {Browne, K}, title = {Asbestos-related mesothelioma: epidemiological evidence for asbestos as a promoter.}, journal = {Archives of environmental health}, volume = {38}, number = {5}, pages = {261-266}, doi = {10.1080/00039896.1983.10544004}, pmid = {6651349}, issn = {0003-9896}, mesh = {Asbestos/*adverse effects ; England ; Epidemiologic Methods ; Family ; Female ; Humans ; Lung Neoplasms/*epidemiology/etiology ; Male ; Mesothelioma/*epidemiology/etiology ; Occupational Diseases/*epidemiology/etiology ; Time Factors ; }, abstract = {A series of 144 cases of mesothelioma among asbestos workers indicated important divergences from the epidemiological pattern shown to exist for asbestos-related lung cancer. Consideration of exposure duration and intensity and the latent period between first exposure and death suggests that asbestos does not act as a complete carcinogen, but as a promoter. A threshold seems probable for both duration and intensity of exposure in the induction of mesothelioma. This threshold may, in part, be related to the passage of fibers from the lungs to the pleura or peritoneum, and would, in any case, be masked in lung cancer by the retention of asbestos in the lungs. Reported cases of mesothelioma in immediate family members indicate the existence of an additional factor in mesothelioma induction, acting earlier in life than the first asbestos exposure.}, } @article {pmid6647226, year = {1983}, author = {Newhouse, ML}, title = {Asbestos-related diseases.}, journal = {The Practitioner}, volume = {227}, number = {1383}, pages = {1399-1411}, pmid = {6647226}, issn = {0032-6518}, mesh = {Asbestos/*adverse effects ; Asbestosis/diagnosis ; Environmental Exposure ; Female ; Humans ; Lung Neoplasms/mortality ; Mesothelioma/mortality ; Occupational Diseases/*etiology ; }, } @article {pmid6641663, year = {1983}, author = {Stevens, RH and Cole, DA and Cheng, HF and Hodge, JA and Will, LA}, title = {Cell-mediated cytotoxicity expressed by lymphoid cells from rats with asbestos-induced peritoneal mesothelioma towards rat fetal cell.}, journal = {Environmental health perspectives}, volume = {51}, number = {}, pages = {91-96}, pmid = {6641663}, issn = {0091-6765}, support = {R01-ES02352-03/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Asbestos/*toxicity ; Cell Survival/drug effects ; Cells, Cultured ; Charcoal ; Cytotoxicity, Immunologic/*drug effects ; Female ; Fetus/immunology ; Immunity, Cellular/drug effects ; Lymphocytes/*immunology ; Male ; Mesothelioma/etiology/*immunology ; Pregnancy ; Rats ; Rats, Inbred F344 ; }, abstract = {Cell-mediated immunity (CMI) directed towards rat fetal cells was evaluated in Fischer F344 young inbred male rats having asbestos-induced peritoneal mesothelioma. The tumors were induced by exposure to Canadian chrysotile B fibers and the CMI delineated by the injury and destruction brought about to 6- to 10-day-old primary fetal cell cultures by the so-called educated peripheral blood lymphoid-cells (PBLC) obtained from the cancer-bearing rats. A significant cytotoxicity was found to be expressed by the PBLCs, suggesting that during the development of mesothelioma, a cellular retrodifferentiation occurs, thereby educating the effectors to recognize a common determinant existing in both the tumor and fetal cells. Educated PBLCs were produced from rats having endodermal tissue cancers (adenocarcinomas of the small bowel, colon and pancreas) and were found to also be cytotoxic to the fetal cultures, yet no injury was apparently inflicted upon cultured mesothelioma target cells by these effectors. These results suggested that the tumor education was specific and that probably a unique and different fetal component was being recognized by the effector cells obtained from the rats with lesions arising either in the mesodermal or endodermal tissue. Further support for this concept was the failure of an antibody, specific to an oncofetal protein existing in endodermal lesions, to apparently recognize any common oncogenic proteins in the mesothelioma. Preliminary studies have also been accomplished which suggests the existence of natural killing immune responses existing to the mesothelioma target cells.(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid6636462, year = {1983}, author = {Harbison, ML and Godleski, JJ}, title = {Malignant mesothelioma in urban dogs.}, journal = {Veterinary pathology}, volume = {20}, number = {5}, pages = {531-540}, doi = {10.1177/030098588302000504}, pmid = {6636462}, issn = {0300-9858}, support = {5T32 RR07000/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Dog Diseases/*pathology ; Dogs ; Female ; Heart Neoplasms/pathology/*veterinary ; Lung/pathology ; Male ; Mesothelioma/pathology/*veterinary ; Pericardium/pathology ; Peritoneal Neoplasms/pathology/*veterinary ; Pleural Neoplasms/pathology/*veterinary ; }, abstract = {Clinical and postmortem materials from six dogs with a diagnosis of malignant mesothelioma were studied retrospectively. The dogs were urban pets with clinical signs of malignant effusions. Two mesotheliomas were pleural, one pericardial, and one peritoneal. Both pleura and pericardium were involved in one dog, and the pleura and peritoneum in another. On gross examination at necropsy, diffuse granular or velvety plaques covering mesothelial surfaces were found in all dogs; firm discrete pleural nodules also were present in two dogs. Neither distant metastases nor areas of deep lung invasion were found. The tumors varied histologically, but the most common type was epithelial with a papillary pattern. Ultrastructurally, the neoplastic cells had prominent surface microvilli, numerous desmosomes, and tonofilaments. Lung tissue from these dogs and from control dogs was evaluated for the presence of ferruginous bodies. Asbestos bodies were found in three of five dogs with mesotheliomas but rarely were found in control dogs. As a group, the mesothelioma cases had significantly more asbestos bodies and total ferruginous bodies than controls. The clinical and morphologic appearance of canine mesothelioma is similar to human mesothelioma and also may be associated with exposure to airborne fibers.}, } @article {pmid6630749, year = {1983}, author = {Hartford, WH}, title = {Asbestos exposure.}, journal = {Journal of the Air Pollution Control Association}, volume = {33}, number = {9}, pages = {820}, pmid = {6630749}, issn = {0002-2470}, mesh = {Asbestos/*adverse effects ; Environmental Exposure ; Female ; Humans ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology ; }, } @article {pmid6316591, year = {1983}, author = {Lam, WK and Kung, TM and Ma, PL and So, SY and Mok, CK}, title = {First report of asbestos-related diseases in Hong Kong.}, journal = {Tropical and geographical medicine}, volume = {35}, number = {3}, pages = {225-229}, pmid = {6316591}, issn = {0041-3232}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Asbestosis/*etiology ; Carcinoma, Small Cell/*etiology ; Hong Kong ; Humans ; Lung Neoplasms/*etiology ; Male ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; Pleural Neoplasms/*etiology ; }, abstract = {There has been no report of malignant mesothelioma or asbestosis in Hong Kong despite the rapid growth of industry in the past few decades. Three patients with malignant pleural mesothelioma and one patient with asbestosis and small cell carcinoma of the lung are reported. All four patients were Chinese in Hong Kong and had a history of occupational exposure to asbestos. Although there is no mining of asbestos in Hong Kong, her rapid industrialization in the past few decades has led to a large population of asbestos-exposed workers in industry. The average annual consumption of crude asbestos (import minus re-export) has grown ten-fold in the past decade to 1.090 tonnes in 1978-79, and the number of workers handling asbestos products was estimated to be 20.000 in 1979. The problem of asbestos related diseases has however been little considered and further epidemiologic studies are warranted.}, } @article {pmid6316498, year = {1983}, author = {Spurny, KR}, title = {Natural fibrous zeolites and their carcinogenicity-a review.}, journal = {The Science of the total environment}, volume = {30}, number = {}, pages = {147-166}, doi = {10.1016/0048-9697(83)90008-6}, pmid = {6316498}, issn = {0048-9697}, mesh = {Aluminum Silicates/*adverse effects/analysis ; Animals ; Humans ; Mesothelioma/analysis/epidemiology/*etiology ; Pleural Neoplasms/analysis/epidemiology/*etiology ; Rats ; Soil/analysis ; Turkey ; Zeolites ; }, abstract = {More than 50 cases of pleural mesothelioma have been reported during the period 1974-1978 in a relatively small area of Turkey, centered in and around the villages of Karain and Tuzköy, in the province of Cappadocia. The area of Karain and Tuzköy is covered with volcanic tuffs, in which asbestos, glass and zeolite fibers were detected. The inhaled dusts of these fibrous materials might be the cause of the high mesothelioma rate. The most important publications on this problem are reviewed and the results of our own examinations are discussed.}, } @article {pmid6315385, year = {1983}, author = {Bignon, J and Jaurand, MC}, title = {Biological in vitro and in vivo responses of chrysotile versus amphiboles.}, journal = {Environmental health perspectives}, volume = {51}, number = {}, pages = {73-80}, pmid = {6315385}, issn = {0091-6765}, mesh = {Animals ; Asbestos/*toxicity ; Asbestos, Amphibole ; Asbestos, Serpentine ; Carcinogens ; Erythrocytes/drug effects ; Humans ; In Vitro Techniques ; Macrophages/drug effects ; Silicon Dioxide/*toxicity ; Subcellular Fractions/drug effects ; }, abstract = {Although all commercial forms of asbestos have been demonstrated to be carcinogenic in animals, so far epidemiological data are controversial concerning what asbestos types are the most carcinogenic and fibrogenic in humans. In order to understand the early cellular events induced by fibrous particles, different in vitro studies (hemolysis, release of enzymes by macrophages, assays on cell culture systems) have been carried out in several laboratories; most of these studies have shown that cell and subcellular in vitro responses were different depending on fiber types: chrysotile versus amphiboles. This presentation compares the results of different laboratories with our data obtained by using a model which modifies the chemistry of the fibers by acid treatment. The acid-leached chrysotile and acid-treated amphibole fibers showed different biological responses in several in vitro systems used in comparison to unleached fibers. These differences in the in vitro reactivity were related to the chemical state of the fibers and might explain the differences in their effects in animals after intrapleural injection as assessed by the percentage of mesothelioma, the latency period, the survival time and the degree of pleural fibrosis. The carcinogenic effect of the fibers is discussed in relation of their in vitro inflammatory or cytotoxic responses.}, } @article {pmid6315378, year = {1983}, author = {Gormley, IP and Bolton, RE and Brown, GM and Davis, JM and Wright, A}, title = {Some observations on the in vitro cytotoxicity of chrysotile prepared by the wet dispersion process.}, journal = {Environmental health perspectives}, volume = {51}, number = {}, pages = {35-39}, pmid = {6315378}, issn = {0091-6765}, mesh = {Animals ; Asbestos/*toxicity ; Asbestos, Serpentine ; Cell Line ; Cell Survival/*drug effects ; Cricetinae ; Cricetulus ; Cytological Techniques ; Dust/adverse effects ; Humans ; Male ; Mesothelioma/etiology ; Mice ; Rats ; }, abstract = {Samples of the chrysotile taken during and after treatment by the wet dispersion process have been tested for their cytotoxic effect in vitro and the results compared with both a UICC chrysotile A sample and a dust prepared from a standard chrysotile textile yarn. Results were obtained from three different in vitro assay systems utilizing P388D1, V79-4 and A549 cells. A sample which still contained the wetting agent used in the wet dispersion process failed to show activity in any of these assays. The other samples, however, were all active with those dusts obtained by milling the final product and by sampling the air of the factory consistently proving significantly more cytotoxic than the standard chrysotile controls. Preliminary results from a parallel in vivo study suggest that these samples are also more active in producing mesotheliomas in rats.}, } @article {pmid6315359, year = {1983}, author = {Pigott, GH and Pinto, PJ}, title = {Effects of nonfibrous minerals in the V79-4 cytotoxicity test.}, journal = {Environmental health perspectives}, volume = {51}, number = {}, pages = {173-179}, pmid = {6315359}, issn = {0091-6765}, mesh = {Aluminum Silicates/toxicity ; Animals ; Asbestos/toxicity ; Asbestos, Crocidolite ; Calcium Carbonate/toxicity ; Cell Line ; Cell Survival/*drug effects ; Cricetinae ; Cricetulus ; Dust/adverse effects ; Lung ; Minerals/*toxicity ; Silicon Dioxide/toxicity ; }, abstract = {The use of the V79-4 system as a primary screen for fiber carcinogenicity is dependent on the observed correlation between cytotoxicity of the test material in the system and mesothelioma following intrapleural injection in animals. This correlation has been established for relatively pure samples of fibrous minerals. The wider application of the system as a screen for industrial dusts may depend on the ability of the system to show an unequivocal response to small yet significant percentages of fibrous dust in the presence of a large excess of nonfibrous material. Some materials tested, including platy minerals, show a response in the test which, while clearly less than that from UICC asbestos samples, could be construed as a positive result. Some, though not all, of these minerals show a nonlinear dose response in the test. This anomalous dose response may aid in the identification of some false positive results but the variety of responses to nonfibrous minerals places a limit on the predictive value of the test mixtures. Results obtained from mixtures of "standard" dust samples suggest this limit is reached at or above 10% fibrous content. Such levels would be significant in terms of human exposure. Extension of the concentration range tested does not improve the predictive value of the test.}, } @article {pmid6315358, year = {1983}, author = {Joseph, LB and Stephens, RE and Ottolenghi, AC and Lipetz, PD and Newman, HA}, title = {Morphological transformation in vitro of normal human fibroblasts by chrysotile.}, journal = {Environmental health perspectives}, volume = {51}, number = {}, pages = {17-22}, pmid = {6315358}, issn = {0091-6765}, mesh = {Asbestos/*toxicity ; Asbestos, Serpentine ; Cell Nucleolus/drug effects/ultrastructure ; Cell Nucleus/drug effects/ultrastructure ; Cells, Cultured ; Cytoplasm/drug effects ; Cytoplasmic Granules/drug effects/ultrastructure ; Fibroblasts/*drug effects/ultrastructure ; Humans ; }, abstract = {Pathologic response of tissue to asbestos in vivo gives rise to fibromatoma, granuloma and mesothelioma. We are attempting to develop a model system in vitro using human cells in order to investigate the possible mechanisms responsible for these pathologies. Within the first 12 hr of exposure to chrysotile, the fibroblasts showed distinctive morphological changes. Cells appeared elongated with occasional vacuolated nuclei and granular cytoplasm. Cells showed no other obvious morphological changes by light microscopy and were serially passaged at confluence. The cells with vacuolated nuclei were successfully serially passaged. Binucleated cells were first observed 48 hr after passaging. As time in culture increased (3 days to 2 weeks) many cells lost their distinctive bipolar properties and developed "stress striations" and multiple vacuoles in the cytoplasm. Multinucleated giant cells (2-11 nuclei/cell) with lobate nucleoli became more numerous. With increasing passages, the confluent cell density decreased and cell size increased. Cells usually had condensed nucleoli and had lost all control of directional growth. Preliminary indications suggest that these in vitro morphological transformations are due--at least in part--to a lack of control over cytokinesis.}, } @article {pmid6312580, year = {1983}, author = {Fredy, M}, title = {[Asbestos and the environment].}, journal = {La semaine des hopitaux : organe fonde par l'Association d'enseignement medical des hopitaux de Paris}, volume = {59}, number = {29-30}, pages = {2100-2102}, pmid = {6312580}, mesh = {Air Pollutants, Occupational/adverse effects/analysis ; Asbestos/*adverse effects ; *Carcinogens, Environmental ; Humans ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Occupational Diseases/*etiology ; Peritoneal Neoplasms/etiology ; Pleural Neoplasms/etiology ; }, } @article {pmid6863663, year = {1983}, author = {Grant, DC and Seltzer, SE and Antman, KH and Finberg, HJ and Koster, K}, title = {Computed tomography of malignant pleural mesothelioma.}, journal = {Journal of computer assisted tomography}, volume = {7}, number = {4}, pages = {626-632}, doi = {10.1097/00004728-198308000-00009}, pmid = {6863663}, issn = {0363-8715}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Humans ; Male ; Mesothelioma/*diagnostic imaging/etiology ; Middle Aged ; Neoplasm Staging ; Occupational Diseases/*diagnostic imaging ; Pleural Neoplasms/*diagnostic imaging/etiology ; *Tomography, X-Ray Computed ; }, abstract = {We tabulated the computed tomographic (CT) findings in 14 consecutive patients who had proven malignant pleural mesotheliomas and were studied over a 3-year period. We also staged the disease in these patients, all of whom were men, aged 40-75 years (mean, 59), and had been exposed to asbestos at work. Common presenting symptoms were shortness of breath or chest pain. Pleural thickening was found on the side of the tumor in all of the patients, characterized as nodular and circumferential (6/14 cases), plaque-like (4/14), or strictly nodular (4/14) in appearance. In addition, 86% of the patients demonstrated contralateral pleural thickening, but these lesions did not prove to be tumor deposits. Other common CT findings in the involved hemithorax included: pleural effusions (79% of cases), lung parenchymal disease (79%), decreased hemithorax size (62%), and pleural calcification (50%). Before the chest scans were performed, 13 patients were felt to have Stage I disease and one to have Stage IV. The CT information revised these opinions: four of the Stage I patients were assigned to Stage II (on the basis of chest wall involvement or enlarged hilar/mediastinal lymph nodes). Therapy was altered in these four cases. In two patients pericardial thickening was seen, but it was not possible to determine if this was due to tumor involvement. We conclude that CT can identify several abnormalities that are commonly associated with mesotheliomas. By demonstrating lesions not detectable on conventional imaging studies, CT may alter staging and therapy in many patients with this disease.}, } @article {pmid6134954, year = {1983}, author = {Archer, VE and Rom, WN}, title = {Trends in mortality of diffuse malignant mesothelioma of pleura.}, journal = {Lancet (London, England)}, volume = {2}, number = {8341}, pages = {112-113}, doi = {10.1016/s0140-6736(83)90104-6}, pmid = {6134954}, issn = {0140-6736}, mesh = {Asbestos/*adverse effects ; Forecasting ; Humans ; Mesothelioma/*mortality ; Pleural Neoplasms/*mortality ; United States ; }, } @article {pmid6886517, year = {1983}, author = {Dark, DS and Pingleton, SK}, title = {Asbestosis and asbestos-related disease.}, journal = {The Journal of the Kansas Medical Society}, volume = {84}, number = {7}, pages = {392-6, 413}, pmid = {6886517}, issn = {0022-8699}, mesh = {Asbestos/*adverse effects ; Asbestosis/*diagnosis ; Carcinoma, Bronchogenic/etiology ; Female ; Humans ; Lung Neoplasms/etiology ; Mesothelioma/diagnosis/*etiology ; Pleural Neoplasms/diagnosis/*etiology ; }, } @article {pmid6664318, year = {1983}, author = {Biava, PM and Fiorito, A and Canciani, L and Bovenzi, M}, title = {[Epidemiology of pleural mesothelioma in the Province of Trieste: the role of occupational exposure to asbestos].}, journal = {La Medicina del lavoro}, volume = {74}, number = {4}, pages = {260-265}, pmid = {6664318}, issn = {0025-7818}, mesh = {Aged ; Asbestos/adverse effects ; Female ; Humans ; Italy ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Diseases/*epidemiology ; Pleural Neoplasms/*epidemiology/etiology ; }, } @article {pmid6344612, year = {1983}, author = {Kagan, E and Jacobson, RJ}, title = {Lymphoid and plasma cell malignancies: asbestos-related disorders of long latency.}, journal = {American journal of clinical pathology}, volume = {80}, number = {1}, pages = {14-20}, doi = {10.1093/ajcp/80.1.14}, pmid = {6344612}, issn = {0002-9173}, mesh = {Aged ; Asbestos/*adverse effects ; Environmental Exposure ; Humans ; Immunoglobulin A/isolation & purification ; Immunoglobulin G/isolation & purification ; Leukemia, Lymphoid/blood/*pathology ; Lymphoma, Large B-Cell, Diffuse/*pathology ; Male ; Middle Aged ; Multiple Myeloma/immunology/*pathology ; Occupational Diseases/etiology/*pathology ; Time Factors ; }, abstract = {We have identified 13 asbestos workers with lymphoplasmacytic neoplasms: six with chronic lymphocytic leukemia, four with IgG myeloma, two with IgA myeloma, and one with histiocytic lymphoma. The subjects' occupations were varied, but all had experienced protracted asbestos exposure (ranging from 3-37 years). Tumor latency periods were similar to other known asbestos-related malignancies and ranged from 16-41 years. Stigmata of asbestos-related pulmonary disease were evident in 12 subjects. Malignant pleural mesotheliomas co-existed with IgG myelomas in two individuals, an association which seems unlikely to be fortuitous. It has been speculated previously that asbestos may be a lymphoid system carcinogen. Our findings strongly support this view and indicate that patients presenting de novo with lymphoproliferative neoplasms should be investigated for previous occupational or environmental exposure to asbestos.}, } @article {pmid6884940, year = {1983}, author = {Höhn, D and Bassey, L and Höhn, BS}, title = {[Pleural mesothelioma. Problems, therapy and results].}, journal = {Fortschritte der Medizin}, volume = {101}, number = {23}, pages = {1091-1096}, pmid = {6884940}, issn = {0015-8178}, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Antineoplastic Agents/therapeutic use ; Female ; Germany, West ; Humans ; Male ; Mesothelioma/diagnosis/*epidemiology/therapy ; Middle Aged ; Pleura/surgery ; Pleural Neoplasms/diagnosis/*epidemiology/therapy ; Prognosis ; Radioisotope Teletherapy ; Sex Factors ; }, abstract = {Pleural mesothelioma caused by asbestos is listed as an occupational disease in the Federal Republic of Germany since 1977. Cases of diffuse pleural mesothelioma must always be suspected to be caused by asbestos. The examination of dust particles in the lung can give a final answer to the question whether asbestos plays an important role in the etiology of a certain case or not. Clinical findings, therapy, and prognosis of pleural mesothelioma are demonstrated by the review of 17 cases of malignant and 3 cases of benign tumors. One case with extraordinary long survival time (still living after 3 years) after probatory thoracotomy only, shows that prognosis even in diffuse pleural mesothelioma must not necessarily always be that bad as generally considered.}, } @article {pmid6879497, year = {1983}, author = {Hillerdal, G and Baris, YI}, title = {Radiological study of pleural changes in relation to mesothelioma in Turkey.}, journal = {Thorax}, volume = {38}, number = {6}, pages = {443-448}, pmid = {6879497}, issn = {0040-6376}, mesh = {Adult ; Asbestos/adverse effects ; Female ; Humans ; Male ; Mesothelioma/*diagnostic imaging/epidemiology/etiology ; Minerals/adverse effects ; Pleura/*diagnostic imaging ; Pleural Neoplasms/*diagnostic imaging/epidemiology/etiology ; Radiography ; Turkey ; }, abstract = {In some villages in central Turkey pleural changes occur as a result of environmental exposure to mineral fibres. In most cases the fibre is asbestos but in some cases the non-asbestos fibre erionite, a zeolite, is responsible. The incidence of malignant mesothelioma is much higher in "erionite villages" than in "asbestos villages" despite similar frequencies of pleural changes. In this study chest radiographs from 466 people from asbestos villages, 549 from erionite villages, and 382 controls were compared. The frequency of pleural calcification was about the same in the two groups of villages studied, but the minor fissures were visible to a greater degree in erionite cases. In people from erionite villages "atypical" pleural calcification, due to calcification of the visceral rather than the parietal pleura, was more common. These differences may indicate that the fibres have different lengths and diameters.}, } @article {pmid6871531, year = {1983}, author = {Edge, JR}, title = {Mesothelioma.}, journal = {British journal of hospital medicine}, volume = {29}, number = {6}, pages = {521-530, 535-6}, pmid = {6871531}, issn = {0007-1064}, mesh = {Air Pollutants, Occupational/adverse effects ; Asbestos/adverse effects ; Humans ; Mesothelioma/*diagnosis/etiology/therapy ; Occupational Diseases/*diagnosis/etiology/therapy ; Pleura/diagnostic imaging/pathology ; Pleural Effusion/cytology ; Pleural Neoplasms/*diagnosis/etiology/therapy ; Radiography ; }, } @article {pmid6850607, year = {1983}, author = {Fischbein, A and Sharma, OK and Selikoff, IJ and Borek, E}, title = {Urinary excretion of modified nucleosides in patients with malignant mesothelioma.}, journal = {Cancer research}, volume = {43}, number = {6}, pages = {2971-2974}, pmid = {6850607}, issn = {0008-5472}, support = {ES 00928/ES/NIEHS NIH HHS/United States ; }, mesh = {Adult ; Age Factors ; Aged ; Female ; Humans ; Male ; Mesothelioma/*urine ; Middle Aged ; Nucleosides/*urine ; RNA, Transfer/urine ; Sex Factors ; }, abstract = {Transfer RNA is the most complex biomacromolecule in both structure and function. The complexity of its structure is caused by a large variety of enzymes which add modifying groups to the four bases after the primary synthesis. The most abundant of these enzymes are the transfer RNA methylases, which add methyl groups at various positions in the macromolecule. These methylating enzymes were found to be, without exception, aberrantly hyperactive in every malignant tumor examined. In turn, every malignant tumor contains a few transfer RNAs that are different in structure from the transfer RNAs in the normal tissue. Again, there is no exception. These are the first qualitatively different biochemical components of every malignant cell, not more or less but different transfer RNAs. The late Alexander Gutman observed that cancer patients excrete in their urine elevated levels of certain methylated bases. From the structure of these bases and our knowledge of their method of synthesis, it became apparent that most of them come from the breakdown of transfer RNA. Their elevation in the urine stems from an extraordinarily high rate of turnover of transfer RNAs in tumor tissue. Highly sophisticated, sensitive methods of analysis were developed for the determination of the modified nucleosides in the urine of cancer patients. When related to the creatinine level of the urine, some of the modified nucleosides and products derived from them were elevated in a large variety of tumors. Perhaps more importantly, it was found that these elevated levels return to normal after effective chemotherapy. Thus, these markers may also be useful in monitoring the effectiveness of therapy. We report here initial studies on the detection of cancer in asbestos workers and possible premalignant conditions in workers with asbestosis.}, } @article {pmid6668506, year = {1983}, author = {Antman, KH and Pomfret, EA and Aisner, J and MacIntyre, J and Osteen, RT and Greenberger, JS}, title = {Peritoneal mesothelioma: natural history and response to chemotherapy.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {1}, number = {6}, pages = {386-391}, doi = {10.1200/JCO.1983.1.6.386}, pmid = {6668506}, issn = {0732-183X}, mesh = {Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Asbestos/adverse effects ; Biopsy ; Blood Coagulation Disorders/chemically induced ; Combined Modality Therapy ; Female ; Humans ; Laparotomy ; Male ; Mesothelioma/etiology/*therapy ; Middle Aged ; Peritoneal Neoplasms/etiology/*therapy ; Retrospective Studies ; Time Factors ; }, abstract = {Twenty-three patients with malignant peritoneal mesothelioma seen at the Dana Farber Cancer Institute and the University of Maryland Cancer Center from 1968 to 1982 were studied to assess the natural history of the disease and the efficacy of current treatment. Asbestos exposure was reported by 57%. Of 18 patients receiving a doxorubicin-containing regimen, 14 had measurable or evaluable disease. One complete response, four partial responses and one regression (in a patient with evaluable but not measurable disease) were observed, ranging in duration from 6 to 36 months. A single patient remains disease free for more than 36 months after subsequent radiotherapy. Significant clotting abnormalities (including disseminated intravascular coagulation, massive thrombosis, fatal pulmonary emboli, Coombs-positive hemolytic anemia, and phlebitis) occurred in 22% of the patients. Trends toward decreased survival were observed for smokers, patients presenting with ascites, and those with stage II-IV disease.}, } @article {pmid6602490, year = {1983}, author = {Reuter, K and Raptopoulos, V and Reale, F and Krolikowski, FJ and D'Orsi, CJ and Graham, S and Smith, EH}, title = {Diagnosis of peritoneal mesothelioma: computed tomography, sonography, and fine-needle aspiration biopsy.}, journal = {AJR. American journal of roentgenology}, volume = {140}, number = {6}, pages = {1189-1194}, doi = {10.2214/ajr.140.6.1189}, pmid = {6602490}, issn = {0361-803X}, mesh = {Aged ; Asbestosis/complications ; *Biopsy, Needle ; Diagnosis, Differential ; Female ; Humans ; Laparotomy ; Male ; Mesothelioma/*diagnosis/pathology/surgery ; Middle Aged ; Neoplasm Metastasis/diagnosis ; Peritoneal Neoplasms/*diagnosis/pathology/surgery ; Prospective Studies ; *Tomography, X-Ray Computed ; *Ultrasonography ; }, abstract = {The diagnosis of peritoneal mesothelioma was made prospectively and noninvasively in four patients with the use of sonography, computed tomography, and sonographically guided fine-needle aspiration biopsy. The imaging methods revealed information similar to the operative findings, with clear superiority of computed tomography over sonography. These noninvasive methods may be used as screening tools, especially among groups or in regional areas with a high risk for asbestos exposure. The findings included soft-tissue masses with invariable involvement of the omentum; small intraperitoneal nodules; thickened peritoneum, mesentery, and bowel wall; pleural plaques; and usually minimal, if any, ascites. Since the differential diagnosis from peritoneal carcinomatosis may be difficult, sonographically (or CT) guided aspiration biopsy is needed to produce diagnostic cytologic specimens. The use of this type of biopsy should obviate surgical exploration.}, } @article {pmid6854431, year = {1983}, author = {Walker, AM and Loughlin, JE and Friedlander, ER and Rothman, KJ and Dreyer, NA}, title = {Projections of asbestos-related disease 1980-2009.}, journal = {Journal of occupational medicine. : official publication of the Industrial Medical Association}, volume = {25}, number = {5}, pages = {409-425}, pmid = {6854431}, issn = {0096-1736}, mesh = {Asbestos/*adverse effects ; Asbestosis/*epidemiology/etiology ; Canada ; Epidemiologic Methods ; Female ; Humans ; Lung Neoplasms/*epidemiology/etiology ; Male ; Mesothelioma/*epidemiology/etiology ; Risk ; United States ; }, abstract = {Approximately 19,000 cases of mesothelioma and 55,000 cases of lung cancer will arise in U.S. men with histories of nontrivial occupational exposure to asbestos. There are approximately 65,000 U.S. men now alive with clinically diagnosable asbestosis. These estimates are based, in the case of the cancer, on estimates of the effective number of asbestos-exposed workers required to produce the current national incidence of mesothelioma. The asbestosis estimates are based on a number of rough measures relating the prevalence of asbestosis to the incidence of mesothelioma, the incidence of compensable asbestosis in other countries, the prevalence of and mortality from pneumoconioses generally, and the number of workers heavily exposed to asbestos.}, } @article {pmid6830709, year = {1983}, author = {Finkelstein, MM}, title = {Mortality among long-term employees of an Ontario asbestos-cement factory.}, journal = {British journal of industrial medicine}, volume = {40}, number = {2}, pages = {138-144}, pmid = {6830709}, issn = {0007-1072}, mesh = {Adult ; Aged ; Asbestosis/*mortality ; Construction Materials ; Humans ; Lung Neoplasms/mortality ; Male ; Mesothelioma/mortality ; Middle Aged ; Ontario ; Time Factors ; }, abstract = {Mortality was studied among a group of 328 employees of an Ontario asbestos-cement factory who had been hired before 1960 and who had been employed for a minimum of nine years. The group of 87 men who had worked in the rock wool/fibre glass operations, or who had been otherwise minimally exposed to asbestos, had mortality rates similar to those of the general Ontario population, while the group of asbestos-exposed employees had all-cause mortality rates double those of the Ontario population, mortality rates due to malignancies five times higher than expected, and deaths attributed to lung cancer eight times more frequent than expected. According to the best evidence available, 10 of 58 deaths among the production workers were due to malignant mesothelioma and 20 to lung cancer. The men dying of mesothelioma were younger than the men dying of lung cancer with mean ages at death of 51 and 64 years respectively. An exposure model was constructed on the basis of the available air sampling data, and individual exposure histories were calculated. These exposure histories were used to investigate the exposure-response relationships for asbestos-associated malignancies.}, } @article {pmid6406317, year = {1983}, author = {Lochner, B and Loddenkemper, R and Claussen, C and Wegener, OH}, title = {[Thoracoscopic and computer tomographic findings in pleural mesotheliomas].}, journal = {RoFo : Fortschritte auf dem Gebiete der Rontgenstrahlen und der Nuklearmedizin}, volume = {138}, number = {5}, pages = {570-576}, doi = {10.1055/s-2008-1055788}, pmid = {6406317}, issn = {1438-9029}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Mesothelioma/*diagnosis/diagnostic imaging ; Middle Aged ; Pleural Effusion/diagnostic imaging ; Pleural Neoplasms/*diagnosis/diagnostic imaging ; *Thoracoscopy ; *Tomography, X-Ray Computed ; }, abstract = {The computer tomographic findings in fifteen patients with histologically confirmed malignant pleural mesotheliomas were analysed. The results were compared with the findings on thoracoscopy and on conventional radiography. On CT, the tumour was not obscured by pleural effusion and the differential diagnosis of masses in the chest wall becomes narrower. Signs of asbestos exposure can be recognised at an early stage. Once the diagnosis has been confirmed histologically, CT demonstrates the tumour clearly. Involvement of the pericardium and mediastinum can be diagnosed with considerable certainty and involvement of the pleura may be assumed if there is an effusion. CT is an advance in the diagnosis of these rare tumours; it aids in arriving at a prognosis and in formulating treatment.}, } @article {pmid6303378, year = {1983}, author = {Poole, A and Brown, RC and Turver, CJ and Skidmore, JW and Griffiths, DM}, title = {In vitro genotoxic activities of fibrous erionite.}, journal = {British journal of cancer}, volume = {47}, number = {5}, pages = {697-705}, pmid = {6303378}, issn = {0007-0920}, mesh = {Aluminum Silicates/*pharmacology ; Animals ; Autoradiography ; Cell Transformation, Neoplastic/*drug effects ; Cells, Cultured ; DNA/biosynthesis ; DNA Repair/*drug effects ; Embryo, Mammalian ; Fibroblasts/drug effects/metabolism ; Humans ; Lung/drug effects/metabolism ; Mice ; Mice, Inbred C3H ; Microscopy, Electron ; Zeolites ; }, abstract = {A high incidence of mesothelioma has been reported from some villages in Cappadocia, Turkey. This type of cancer is usually associated with the inhalation of asbestos, but on the basis of the most prevalent fibre in the dust from these villages, the Turkish outbreak has been attributed to the inhalation of zeolite fibres. A counter hypothesis, based on the detection of very small quantities of chrysotile and tremolite in strata samples and human lung tissue, postulates a significant role of these minerals as one of several factors contributing to pleural disease. A respirable fraction of erionite, (from Oregon, USA, but with similar characteristics to the fibres found in Turkey), has some in vitro genotoxic properties associated with many conventional carcinogens. In this study these fibres caused an increase in morphological transformation and unscheduled DNA repair synthesis (UDS) in C3H10T1/2 cells and UDS in the human lung cell line--A549. It is therefore suggested that exposure to fibrous erionite alone may be sufficient to cause the high incidence of pleural tumours observed in Turkey.}, } @article {pmid6299326, year = {1983}, author = {Browne, K and Smither, WJ}, title = {Asbestos-related mesothelioma: factors discriminating between pleural and peritoneal sites.}, journal = {British journal of industrial medicine}, volume = {40}, number = {2}, pages = {145-152}, pmid = {6299326}, issn = {0007-1072}, mesh = {Asbestos/*adverse effects ; Asbestos, Crocidolite ; Female ; Humans ; Male ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; Peritoneal Neoplasms/*etiology ; Pleural Neoplasms/*etiology ; Time Factors ; }, abstract = {Up to the end of 1980, 144 confirmed cases of mesothelioma were identified among employees of an organisation using asbestos in manufacturing and insulation. The primary site was peritoneal in 74 cases, pleural in 66, and undetermined in four. All employees had been exposed to amphibole asbestos, and evidence from different factories confirmed the predominant role of crocidolite in the production of mesothelioma. The ratio of pleural to peritoneal sites showed a continuous change when related to the year of first exposure, varying from 5:1 pleural to peritoneal before 1921 to 1:3 after 1950. The strong temporal relationship appeared to reflect progressive dust suppression, including the non-fibrous dusts present in insulation materials and perhaps also the degree to which the fibres had been opened. Other predisposing factors were related to the degree of individual exposure, the peritoneal site being associated preferentially with longer and heavier exposures.}, } @article {pmid6863756, year = {1983}, author = {Enterline, PE}, title = {Cancer produced by nonoccupational asbestos exposure in the United States.}, journal = {Journal of the Air Pollution Control Association}, volume = {33}, number = {4}, pages = {318-322}, doi = {10.1080/00022470.1983.10465580}, pmid = {6863756}, issn = {0002-2470}, mesh = {Air Pollutants/*poisoning ; Asbestos/*poisoning ; Environmental Exposure ; Female ; Humans ; Lung Neoplasms/epidemiology/*etiology/mortality ; Male ; Mesothelioma/epidemiology/*etiology/mortality ; United States ; }, } @article {pmid6367302, year = {1983}, author = {Grimm, HG}, title = {[Findings in the bronchopulmonary system of workers employed in the industrial production and processing of synthetic mineral fibers].}, journal = {Zentralblatt fur Bakteriologie, Mikrobiologie und Hygiene. 1. Abt. Originale B, Hygiene}, volume = {177}, number = {3-4}, pages = {188-236}, pmid = {6367302}, issn = {0174-3015}, mesh = {Adult ; Age Factors ; Aged ; Bronchitis/epidemiology ; Chronic Disease ; Dust/*adverse effects ; Female ; Glass/*adverse effects ; Humans ; Lung Neoplasms/epidemiology ; Male ; Middle Aged ; Minerals/*adverse effects ; Occupational Diseases/*epidemiology ; Pneumoconiosis/epidemiology ; Respiratory Tract Diseases/*epidemiology ; Risk ; Smoking ; Time Factors ; }, abstract = {This paper reports on the evaluation of 21 epidemiological studies concerning investigations in the Man-Made Mineral Fibers (MMF) industries. First conditions of exposure were described. Concentrations of respirable fibers at the production and further treatment of MMF in older plants were in average about a few fibers per cm3, today in most cases remarkable below 1 fiber/cm3. In the old factories also there has been an exposure with very fine fibers with a diameter below 1 micron and this is comparable from its amount with the conditions nowadays. About 55000 workers exposed to MMF were investigated, most of them handling glass fibers. Several thousands of this workforce had a duration of exposure of 20 years or more and a latency time of 30 years or more. No case of mesothelioma was found. A most of the identified cases of pneumoconiosis could be attached to a prior or a concomitant exposure to silica if the occupational exposure was carefully examined. At the recent time there is no wellfounded suspicion that pneumoconiosis is caused by the exposure in the MMF-industries. A few authors supposed, that unspecific structural changes of the lung as occuring also in a greater amount in dependency of smoking habits and age are found more frequently among the employees of this industry than among the common population. Neither the workers with such unspecific structural changes of the lung nor the other members of the workforces had prejudices of lung function. At present time a risk due to MMF to get sick with cancer of the bronchopulmonic system, especially with lung cancer can neither be proved nor be excluded. The epidemiological studies carried out until now were not capable to point out a possibly existing risk in such a ordner of magnitude. It is uncertain if it will be feasable to prove such a risk by using more subtilized methods. This depends at one side on the possibility of clearing up and registering the confounding risk factors. On the other side it must be considered, that the exposure with fibrous dusts even in the old MMF-factories was very much lower than the exposure in the asbestos-industry. It is indispensable to take into account the most important confounding risk factors (smoking habits, preexposure and concomitant exposure with dangerous working materials) in further epidemiological investigations.}, } @article {pmid6316484, year = {1983}, author = {Huuskonen, MS and Järvisalo, J and Koskinen, H and Nickels, J and Räsänen, J and Asp, S}, title = {Preliminary results from a cohort of workers exposed to wollastonite in a Finish limestone quarry.}, journal = {Scandinavian journal of work, environment & health}, volume = {9}, number = {2 Spec No}, pages = {169-175}, doi = {10.5271/sjweh.2438}, pmid = {6316484}, issn = {0355-3140}, mesh = {Adult ; Aged ; Antibodies, Antinuclear/immunology ; *Calcium Compounds ; Female ; Finland ; Follow-Up Studies ; Humans ; Male ; Mesothelioma/diagnosis ; Middle Aged ; Neoplasms/mortality ; Occupational Diseases/*immunology/mortality ; Peptidyl-Dipeptidase A/blood ; Pulmonary Fibrosis/epidemiology/immunology ; Retroperitoneal Neoplasms/diagnosis ; Rheumatoid Factor/immunology ; *Silicates ; Silicic Acid/adverse effects/*immunology ; Silicon Dioxide/*immunology ; }, abstract = {Wollastonite metasilicate fibers are rather similar in form, length, and diameter, but mineralogically different, to amphibole asbestos fibers. We have studied immunologic findings from 46 men exposed to wollastonite at a limestone quarry for at least 10 years. These workers showed a higher prevalence of positive serum rheumatoid factors than blood donors did. This finding resembles the one detected among asbestos workers. The group of wollastonite workers with radiological signs of pulmonary fibrosis had activities of serum angiotensin-converting enzyme that were similar to those of wollastonite workers without fibrosis. A mortality study of 238 quarry workers with 5,769 person-years was, as expected, nonpositive. It was interesting that one woman with 20 years of exposure to wollastonite and with no other known exposure to fibers revealed a malignant retroperitoneal mesenchymal tumor 30 years after the initial exposure. This kind of very rare tumor is difficult to distinguish from mesothelioma. However, this is only one case, and it is impossible to draw any definite conclusions.}, } @article {pmid6844893, year = {1983}, author = {Rüttner, JR}, title = {[Malignant mesothelioma and asbestos].}, journal = {Schweizerische medizinische Wochenschrift}, volume = {113}, number = {10}, pages = {346-351}, pmid = {6844893}, issn = {0036-7672}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Environmental Exposure ; Humans ; Mesothelioma/epidemiology/*etiology ; Middle Aged ; Pleural Neoplasms/epidemiology/*etiology ; Switzerland ; }, abstract = {Malignant mesothelioma is a rare neoplasm of rapidly lethal course arising primarily in the pleura and less often in the peritoneum. In the majority of cases the disease is closely related to occupational exposure to asbestos. The latency period, calculated from the first contact with asbestos to the appearance of mesothelioma, is generally in the order of 20 years or more irrespective of the duration of exposure. A causal relationship can be established with certainty only by a careful history and positive tissue analysis for the presence of asbestos. The author's own series of 48 pleural mesotheliomas comprises 39 cases involving occupational exposure to asbestos, 6 others with asbestos demonstrable in pulmonary tissue but no discernible source in the history, and 3 where no relation to asbestos could be established at all. Although a dose-response relation may be assumed for asbestos as for all other carcinogens, the lack of data on asbestos dust concentrations at former places of work rendered determination of the minimal noxious dose difficult or impossible. It also remains unclear whether the various asbestos types, such as chrysotile and amphiboles, differ in pathogenic effect. It is hoped that careful registration and continuing study of mesotheliomas will shed further light on their relationship to asbestos and on the possible hazards of the mineral to the general population.}, } @article {pmid6837538, year = {1983}, author = {Ehrenreich, T and Selikoff, IJ}, title = {Diseases associated with asbestos exposure. Diagnostic perspectives in forensic pathology.}, journal = {The American journal of forensic medicine and pathology}, volume = {4}, number = {1}, pages = {63-72}, doi = {10.1097/00000433-198303000-00007}, pmid = {6837538}, issn = {0195-7910}, mesh = {Asbestos/*adverse effects ; *Environmental Exposure ; Forensic Medicine ; Humans ; Lung Neoplasms/*diagnosis/etiology/pathology ; Mesothelioma/*diagnosis/etiology/pathology ; Pleural Diseases/*diagnosis/etiology/pathology ; Pleural Neoplasms/*diagnosis/etiology/pathology ; }, abstract = {Asbestos, a fibrous mineral, has unique physical and chemical properties, including resistance to heat, acids, and other chemicals; flexibility; and great tensile strength. The fibers subdivide into unit fibrils of molecular dimensions, resulting in a vast mineral surface area which has a direct bearing on its unusual features and its numerous applications. Its biological effects, which include fibrogenesis and carcinogenesis, may be related to the cellular reaction, to its large specific surface, or to the size and shape of the fibers. Its oncogenic action may be multiplied by other carcinogens, principally cigarette smoking. There is clinical, pathologic, and epidemiologic evidence that exposure to asbestos, following a long latent period, constitutes an important health hazard. Direct occupational exposure, followed by a long lapsed period after the initial exposure, is associated with pleural plaques and pleural effusion, pulmonary parenchymal fibrosis (asbestosis), pulmonary carcinoma, pleural and peritoneal mesothelioma, and other neoplasms. Indirect exposure may also entail an increased risk of lung disease or mesothelioma or both. Medicolegal investigation of suspected cases includes a lifetime occupational history, clinical history including smoking habits, radiological findings, clinical evidence of asbestosis, and may require detection of asbestos tissue burden.}, } @article {pmid6679617, year = {1983}, author = {Baba, K}, title = {Indications of an increase of occupational pleural mesothelioma in Japan.}, journal = {Journal of UOEH}, volume = {5}, number = {1}, pages = {3-15}, doi = {10.7888/juoeh.5.3}, pmid = {6679617}, issn = {0387-821X}, mesh = {Adult ; Aged ; Asbestosis/complications ; Female ; Humans ; Industry ; Japan ; Male ; Mesothelioma/complications/*epidemiology ; Middle Aged ; Occupational Diseases/*epidemiology ; Pleural Neoplasms/complications/*epidemiology ; }, abstract = {In order to obtain an epidemiological picture of occupational pleural malignant mesotheliomas in Japan, the author surveyed the Annual of Pathological Autopsy Cases (published by the Japanese Pathological Society) from 1974 through 1980. Two hundred and twenty-two malignant mesotheliomas (0.114% of all autopsy cases) were found in that period. One hundred and forty-five cases (0.074%) of them were of pleural origin. Until 1977, there were no pleural malignant mesotheliomas associated with asbestosis, but there were one in 1978, three in 1979 and two in 1980. Two of them were housewives and the others were a ship builder, a welder, a ceramist and a steel factory worker. Two lived in Sakae City, and the others in Kure City, Kaizuka City, Nagasaki City and Kanagawa Prefecture, where large shipyards are located. Compared to the Western countries, there is a time lag of 10 to 20 years in the increase of consumption of asbestos in Japan, where the increase has occurred rapidly after World War II. The epidemiological picture obtained by this study clearly states that the number of occupational pleural malignant mesotheliomas began to increase in the past few years in Japan.}, } @article {pmid6346786, year = {1983}, author = {Nishimoto, Y and Ohno, T and Saito, K}, title = {Pseudomesotheliomatous carcinoma of the lung with histochemical and immunohistochemical study.}, journal = {Acta pathologica japonica}, volume = {33}, number = {2}, pages = {415-423}, doi = {10.1111/j.1440-1827.1983.tb01428.x}, pmid = {6346786}, issn = {0001-6632}, mesh = {Carcinoembryonic Antigen/analysis ; Histocytochemistry ; Humans ; Hyaluronic Acid/analysis ; Immunoenzyme Techniques ; Lung/pathology ; Lung Neoplasms/analysis/*pathology ; Male ; Mesothelioma/analysis/*pathology ; Middle Aged ; Periodic Acid-Schiff Reaction ; }, abstract = {An autopsy case of pseudomesotheliomatous carcinoma of the right lung in a 56-year-old man occupationally exposed to stone dust is presented. From open biopsy specimens in which polyhedral epithelium-like cells appeared arranged in nests, sheets, and trabecula without apparent tubular pattern, a malignant pleural mesothelioma was suspected. At autopsy, the right pleural cavity was obliterated by the tumor mass which covered the collapsed pulmonary parenchyma and was clearly demarcated from it. The gross appearance of the tumor was similar to that of malignant pleural mesothelioma. Histologically, marked interstitial fibrosis of the subpleural parenchyma of both lungs was observed, and the tumor tissue was interspersed in the parenchyma adjacent to the tumor mass. The tumor showed both intracytoplasmic and intercellular positive materials with colloidal iron, alcian blue (pH 2.5), and toluidine blue stains, which entirely disappeared after streptomyces hyaluronidase digestion. A small amount of intracytoplasmic PAS-positive material resistant to diastase digestion was also observed. Immunohistochemical staining for carcinoembryonic antigen, which is said to be negative in malignant pleural mesothelioma, was positive intracellularly. There were no histologic findings indicating asbestos exposure. From these findings, the authors made a diagnosis of poorly differentiated adenocarcinoma, which was characterized by the production of hyaluronic acid.}, } @article {pmid6848876, year = {1983}, author = {Goodman, LR}, title = {Radiology of asbestos disease.}, journal = {JAMA}, volume = {249}, number = {5}, pages = {644-646}, pmid = {6848876}, issn = {0098-7484}, mesh = {Asbestosis/*diagnostic imaging ; Diagnosis, Differential ; Humans ; Lung Neoplasms/diagnostic imaging ; Mesothelioma/diagnostic imaging ; Radiography, Thoracic ; Tomography, X-Ray Computed ; }, } @article {pmid6297532, year = {1983}, author = {Berry, G and Newhouse, ML}, title = {Mortality of workers manufacturing friction materials using asbestos.}, journal = {British journal of industrial medicine}, volume = {40}, number = {1}, pages = {1-7}, pmid = {6297532}, issn = {0007-1072}, mesh = {Adult ; Asbestos/*adverse effects ; Asbestos, Serpentine ; Female ; Gastrointestinal Neoplasms/mortality ; Humans ; Lung Neoplasms/mortality ; Male ; Mesothelioma/etiology/*mortality ; Middle Aged ; Neoplasms/etiology/*mortality ; Occupational Diseases/etiology/*mortality ; Pleural Neoplasms/mortality ; United Kingdom ; }, abstract = {A mortality (1942-80) study was carried out on 13460 workers of a factory producing friction materials. The only type of asbestos used was chrysotile, except during two well-defined periods before 1945 when crocidolite was used, and over 99% of the population was traced. Compared with national death rates there were no detectable excesses of deaths due to lung cancer, gastrointestinal cancer, or other cancers; 11 deaths were due to pleural mesothelioma. A case-control study was carried out on deaths due to mesothelioma; this showed that eight workers had been exposed to crocidolite and another was possibly exposed intermittently to crocidolite. The other two had been employed for most of their working lives outside the factory, and their mesotheliomas could not be definitely attributed to exposure to chrysotile. Limiting the study to cases and controls who had exposure to 5 fibres/ml of chrysotile asbestos it was found that five of the six cases compared with two of the 10 controls had also been exposed to crocidolite. The probability (1:36) of this occurring were there no association with crocidolite is most unlikely. A case-control study was also carried out on deaths due to lung cancer and gastrointestinal cancer to investigate the dose-response relationships between these tumours and exposure to chrysotile. Measured and estimated fibre concentrations were available for the different jobs over the period of the study. No dose-response relationships were observed, but the exposures were low with only 5% of men accumulating 100 fibre-years/ml. The experience at this factory over a 40-year period showed that chrysotile asbestos was processed with no detectable excess mortality.}, } @article {pmid6869375, year = {1983}, author = {Mancuso, TF}, title = {Mesothelioma among machinists in railroad and other industries.}, journal = {American journal of industrial medicine}, volume = {4}, number = {4}, pages = {501-513}, doi = {10.1002/ajim.4700040404}, pmid = {6869375}, issn = {0271-3586}, mesh = {Aged ; Asbestos/toxicity ; Humans ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Occupational Diseases/*epidemiology ; Pleural Neoplasms/*epidemiology ; *Railroads ; Time Factors ; United States ; }, abstract = {The first phase of the exploration of occupation-related cancer among machinists was a retrospective review of deaths among members of the International Association of Machinists and Aerospace Workers in 1973, in which mesotheliomas were identified in workers in railroad and other industries. The second phase of the study initiated in 1982 was the establishment of a cohort study of machinists, employed for railroad company A, who were alive in January 1954. The cohort consisted of 197 machinists who had been employed by the same railroad prior to 1935 and observed to 1982. Causes of death were identified for 132 of the cohort. There were 18 alive and 47 not traced. Among the 29 cancer deaths, there were nine mesotheliomas and one endothelioma of the pleura. Additional retrospective surveys of deaths among members of the railroad lodges of the international union, together with the cohort study, identified a total of 42 mesotheliomas, two endotheliomas of the pleura, and two cancers of the pleura among former railroad machinists. Among the machinists employed in other industries, 16 mesotheliomas and six cancers of the pleura were identified. For decades, machinists, by the nature of their craft, have had a high risk of occupation-related cancer due to asbestos exposure.}, } @article {pmid6866894, year = {1983}, author = {Irisson, M and Velardocchio, JM and Viallat, JR and Boutin, C}, title = {[Clinical aspects and course of 38 cases of malignant pleural mesothelioma observed in the Marseilles region].}, journal = {Le Poumon et le coeur}, volume = {39}, number = {1}, pages = {5-11}, pmid = {6866894}, issn = {0032-5821}, mesh = {Adult ; Aged ; Asbestosis/complications ; Biopsy, Needle ; Cytodiagnosis ; Female ; Humans ; Male ; Mesothelioma/*diagnosis/epidemiology/pathology ; Middle Aged ; Neoplasm Metastasis ; Pleural Neoplasms/*diagnosis/epidemiology/pathology ; Thoracoscopy ; }, abstract = {Epithelial or mixed mesotheliomas were detected in 38 patients in the region of Marseilles over a period of 9 years. Though an occupational element was involved in 80% of cases, no history of contact with asbestos could be obtained in certain of the patients. Confirmation of diagnosis requires wide pleural biopsies, because of the high level of false negatives and false positives from cytology and pleural needle biopsy. Hyaluronic acid levels are significant only when they are markedly enhanced. Local and regional tumor spread provides an aid to prognosis, but authentic metastases, with further worsening of prognosis, were detected in more than 75% of patients while still alive. Nodules appeared along the course of punctures of drainage tubes or in thoracotomy scars in 56% of cases, and appear to be a very frequent and characteristic feature of mesothelioma. Their therapy involves preventive irradiation.}, } @article {pmid6846340, year = {1983}, author = {Lebovits, AH and Chahinian, AP and Holland, JC}, title = {Exposure to asbestos: psychological responses of mesothelioma patients.}, journal = {American journal of industrial medicine}, volume = {4}, number = {3}, pages = {459-466}, doi = {10.1002/ajim.4700040306}, pmid = {6846340}, issn = {0271-3586}, support = {1R01-ES02578/ES/NIEHS NIH HHS/United States ; }, mesh = {*Asbestos ; Environmental Exposure ; Female ; Humans ; Male ; Mesothelioma/*etiology/psychology ; Middle Aged ; Risk ; *Smoking ; }, abstract = {Thirty-eight patients with a diagnosis of malignant mesothelioma participated in a semi-structured interview to evaluate asbestos exposure, acquisition of increased risk information, and retrospective reporting of cognitive and behavioral reactions (particularly smoking behavior) to risk information. Twenty-eight patients (74%) had direct occupational contact with asbestos, and six patients (16%) reported indirect nonoccupational exposure to asbestos. Only two (10%) of the directly exposed patients acquired risk information from professional sources prior to diagnosis of mesothelioma. The most frequently reported reaction to learning of increased risk of cancer was a denial of the risk by minimizing personal exposure. Few patients reported being concerned about the information of increased risk. Smoking behavior did not change as a result of risk information, nor was there any increase in visits to physicians. Guidelines for psychosocial management of at-risk groups are recommended.}, } @article {pmid6844696, year = {1983}, author = {Borek, E and Sharma, OK and Waalkes, TP}, title = {New applications of urinary nucleoside markers.}, journal = {Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer}, volume = {84}, number = {}, pages = {301-316}, doi = {10.1007/978-3-642-81947-6_23}, pmid = {6844696}, issn = {0080-0015}, mesh = {Adult ; Aging ; Burkitt Lymphoma/urine ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Methylation ; Neoplasms/*urine ; Nucleosides/*urine ; RNA, Neoplasm/metabolism ; RNA, Transfer/metabolism ; Reference Values ; Sex Factors ; }, abstract = {In order to extend the usefulness of the quantitation of urinary nucleoside markers, studies were undertaken to explore the adaptability of such determinations for early detection in cancer-prone populations such as asbestos workers. Another study was aimed at exploring the usefulness of therapy in individual patients. During these studies, two heretofore unknown phenomena serendipitously emerged which expand the versatility of the marker determinations: (a) radiation damage in animals and humans causes an excretion of urinary BAIB which from preliminary studies appears to be proportional to the irradiation burden, and (b) lead poisoning in the human also produces BAIB excretion. Some of the practical uses of these determinations are self-evident. Among 13 asbestos workers without clinical symptoms, eight were found to have significant elevations of the marker levels. Nine asbestos workers with diagnosed mesothelioma all excreted two or more markers at high levels. Some of the psi levels were the highest seen. Currently the diagnosis of mesothelioma is difficult and painful, requiring a rib resection; however, an asbestos worker with such elevations--provided small cell carcinoma of the lung is ruled out--can be seriously suspected of having mesothelioma. In a study of the usefulness of the markers in following therapy of trophoblastic disease, these markers were determined in women with incipient invasive hydatidiform mole. After curettage, the nucleoside markers indicated absence of residual disease but the usual marker, HCG, was still markedly elevated. The women were followed up for 2 years and were found to remain symptom-free. Therefore the source of the nucleoside markers is cleared more rapidly than that of HCG.}, } @article {pmid6674859, year = {1983}, author = {Warnock, ML and Kuwahara, TJ and Wolery, G}, title = {The relation of asbestos burden to asbestosis and lung cancer.}, journal = {Pathology annual}, volume = {18 Pt 2}, number = {}, pages = {109-145}, pmid = {6674859}, issn = {0079-0184}, support = {ES02117/ES/NIEHS NIH HHS/United States ; }, mesh = {Adenocarcinoma/etiology/pathology ; Adult ; Aged ; Asbestos/adverse effects/*analysis ; Asbestosis/etiology/*pathology ; Bronchi/pathology ; Carcinoma/pathology ; Dust/analysis ; Female ; Humans ; Lung/analysis/pathology ; Lung Diseases/etiology/pathology ; Lung Neoplasms/etiology/*pathology ; Male ; Mesothelioma/etiology/pathology ; Middle Aged ; Pulmonary Fibrosis/etiology/pathology ; }, } @article {pmid6672219, year = {1983}, author = {Gough, M}, title = {Sources and interpretation of asbestos exposure data.}, journal = {Journal of toxicology. Clinical toxicology}, volume = {21}, number = {1-2}, pages = {211-235}, doi = {10.3109/15563658308990418}, pmid = {6672219}, issn = {0731-3810}, mesh = {Asbestos/*toxicity ; Environmental Exposure ; Female ; Humans ; Lung Neoplasms/etiology ; Male ; Mesothelioma/etiology/mortality ; Risk ; }, } @article {pmid6671361, year = {1983}, author = {Becklake, MR}, title = {Occupational lung disease--past record and future trend using the asbestos case as an example.}, journal = {Clinical and investigative medicine. Medecine clinique et experimentale}, volume = {6}, number = {4}, pages = {305-317}, pmid = {6671361}, issn = {0147-958X}, mesh = {Asbestos/*toxicity ; Epidemiology ; Humans ; Lung Diseases/*etiology ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Occupational Diseases/*etiology ; Pleural Diseases/etiology ; Pulmonary Fibrosis/etiology ; Tobacco Use Disorder/complications ; }, abstract = {Knowledge and understanding of the occupational lung diseases in the post World War II era has come from clarification of the underlying disease mechanisms (attributable to spectacular developments in the laboratory sciences in particular physiology) and from epidemiologic studies clarifying their relationship to occupational exposure. In the case of exposure to asbestos, the risk for all the serious asbestos-related pulmonary diseases (fibrosis of the lungs and pleura, as well as cancer of these organs) has been shown to increase with increasing exposure. However, it is evident that there are considerable differences in risk between workforces, differences believed to be the consequence of differences in the physical (i.e. size) as well as chemical characteristics of the dust clouds to which the different work forces are exposed. Two key questions as yet unanswered are the risk at low level exposure, and the critical characteristics of fibers, physical and/or chemical, which determine pathogenicity. Answers to these questions will determine the future role of this mineral in our society.}, } @article {pmid6624744, year = {1983}, author = {Sepulveda, MJ and Merchant, JA}, title = {Roentgenographic evidence of asbestos exposure in a select population of railroad workers.}, journal = {American journal of industrial medicine}, volume = {4}, number = {5}, pages = {631-639}, doi = {10.1002/ajim.4700040504}, pmid = {6624744}, issn = {0271-3586}, mesh = {Aged ; Asbestosis/*diagnostic imaging/etiology ; Humans ; Lung/diagnostic imaging ; Mesothelioma/*diagnostic imaging/etiology ; Middle Aged ; Occupational Diseases/*diagnostic imaging/etiology ; Pleural Neoplasms/*diagnostic imaging/etiology ; Radiography ; *Railroads ; Risk ; Smoking ; }, abstract = {A volunteer population of 266 current and former railroad workers was examined with posteroanterior and oblique chest roentgenograms, and a comprehensive occupational smoking history. Seventy-five percent of participants were over the age of 60, and 80% had fewer than 10 years of railroad-related asbestos exposure. Roentgenographic evidence of asbestosis was found in only six workers (2%), whereas 20% had one or more pleural changes. Radiological abnormalities were related to latency period, age, and occupation, but not to smoking habit. While selection factors qualify the results of this study, the findings support the exposure and suggest a past and future history of asbestos mortality and morbidity among steam era railway workers.}, } @article {pmid6613538, year = {1983}, author = {Schwechheimer, K and Butzengeiger, M}, title = {Brain metastases in malignant fibrous mesothelioma. Case report and review of the literature.}, journal = {Acta neuropathologica}, volume = {60}, number = {3-4}, pages = {301-304}, pmid = {6613538}, issn = {0001-6322}, mesh = {Aged ; Brain Neoplasms/pathology/*secondary ; Humans ; Male ; Mesothelioma/pathology/*secondary ; Pleural Neoplasms/pathology ; }, abstract = {A malignant fibrous mesothelioma is reported in a man of 70, arising from the left pleura with widespread metastases in the regional lymph nodes, diaphragm, chest wall, adrenal glands, and brain. Asbestos bodies were not found. Histologically, the primary tumor consisted of interlacing bundles of spindle-shaped malignant cells with a considerable number of mitoses. In the brain two large metastases occurred. Macroscopically, the occipital metastasis looked like an intracranial hemorrhage. Microscopically, the metastases mimicked the pattern of a glioblastoma multiforme. The present case is discussed against the background of the pertinent literature.}, } @article {pmid6605550, year = {1983}, author = {Riani Costa, JL and Ferreira, YM and Mendes, R}, title = {[Asbestos and disease: introduction to the problem in Brazil].}, journal = {AMB : revista da Associacao Medica Brasileira}, volume = {29}, number = {1-2}, pages = {18-21}, pmid = {6605550}, issn = {0102-843X}, mesh = {Asbestos/*adverse effects ; Asbestosis/*etiology ; Brazil ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; *Mining ; Pleural Neoplasms/*etiology ; }, } @article {pmid6347054, year = {1983}, author = {Mossman, B and Light, W and Wei, E}, title = {Asbestos: mechanisms of toxicity and carcinogenicity in the respiratory tract.}, journal = {Annual review of pharmacology and toxicology}, volume = {23}, number = {}, pages = {595-615}, doi = {10.1146/annurev.pa.23.040183.003115}, pmid = {6347054}, issn = {0362-1642}, mesh = {Animals ; Asbestos/*adverse effects/analysis/toxicity ; Cell Membrane/physiology ; Erythrocytes/ultrastructure ; Hemolysis ; Humans ; Mesothelioma/*etiology ; Neoplasms, Experimental/etiology ; Polycyclic Compounds/*toxicity ; Respiratory Tract Neoplasms/*etiology ; }, } @article {pmid6303618, year = {1983}, author = {Bignon, J and Monchaux, G and Chameaud, J and Jaurand, MC and Lafuma, J and Masse, R}, title = {Incidence of various types of thoracic malignancy induced in rats by intrapleural injection of 2 mg of various mineral dusts after inhalation of 222Ra.}, journal = {Carcinogenesis}, volume = {4}, number = {5}, pages = {621-628}, doi = {10.1093/carcin/4.5.621}, pmid = {6303618}, issn = {0143-3334}, mesh = {Animals ; Asbestos/*toxicity ; Bronchial Neoplasms/etiology ; Carcinoma/etiology ; *Cocarcinogenesis ; Lung Neoplasms/*etiology ; Male ; Mesothelioma/etiology ; Pleural Neoplasms/etiology ; Quartz/toxicity ; Radon/*adverse effects ; Rats ; Silicon Dioxide/toxicity ; }, abstract = {After inhalation of 222Ra at equilibrium with radon daughters, male Sprague-Dawley rats were inoculated intrapleurally with 2 mg of unleached or acid-leached asbestos fibres or glass fibres or quartz. The additive co-carcinogenic effects of this type of insult were demonstrated by the increased incidence of malignant thoracic tumours. In rats given mineral materials, bronchopulmonary carcinomas and mixed carcinomas were observed, as well as typical mesotheliomas and combined pulmonary pleural tumours, whereas in control rats inhaling radon alone, only bronchopulmonary carcinomas occurred. No significant differences in tumour incidence were observed between the groups of animals given the different types of dusts, but statistically significant differences were noted in survival times, according to the histological type of tumour. The co-carcinogenic effects of an insult of the pleura by mineral dusts following inhalation of radon are discussed in relation to a possible tumour-promoting effect by these agents.}, } @article {pmid6299515, year = {1983}, author = {Katada, H and Higashiguchi, R and Maruyama, H and Emi, Y and Yokose, Y and Takahashi, S and Mikami, R and Konishi, Y}, title = {Effects of chrysotile asbestos on lung and pleural carcinogenesis of N-bis(2-hydroxypropyl)nitrosamine in rats.}, journal = {Cancer letters}, volume = {17}, number = {3}, pages = {313-320}, doi = {10.1016/0304-3835(83)90169-6}, pmid = {6299515}, issn = {0304-3835}, mesh = {Animals ; Asbestos/*toxicity ; Asbestos, Serpentine ; Carcinogens/*toxicity ; Drug Interactions ; Lung/drug effects/*pathology ; Lung Neoplasms/*chemically induced/pathology ; Male ; Neoplasms, Experimental/pathology ; Nitrosamines/*toxicity ; Pleura/drug effects/*pathology ; Pleural Neoplasms/*chemically induced/pathology ; Rats ; Rats, Inbred Strains ; }, abstract = {The effects of chrysotile asbestos on lung and pleural carcinogenesis by N-bis(2-hydroxypropyl)nitrosamine (DHPN) in male Wistar rats were studied. Chrysotile, 30 mg per rat, was injected into the left pleural cavity and 3 g/kg body wt. DHPN was injected once into the abdominal cavity. Lung tumors (adenoma, adenocarcinoma, squamous cell carcinoma, and combined carcinoma) occurred at the highest incidence (100%). Adenocarcinoma was seen in 4 of 11 (36%) rats killed at 35 weeks and in 6 of 12 (50%) rats killed at 52 weeks, squamous cell carcinoma occurred in 1 of 11 (9%) rats killed at 35 weeks and 3 of 12 (25%) rats killed at 52 weeks, and mixed carcinoma was seen in 1 of 12 (8%) rats killed at 52 weeks, which received chrysotile and DHPN. Adenocarcinoma was seen in 9 of 11 (82%) rats which received DHPN only and killed at 52 weeks. Mesotheliomas were seen in 2 of 11 (18%) rats, killed at 35 weeks, and 3 of 12 (25%) rats, killed at 52 weeks, which received chrysotile and DHPN. Hyaline thickening of the pleura was seen in 100% of rats receiving chrysotile. Mesothelial cell hyperplasia and adenomatous and/or fibromatous growth of the mesothelium were seen in the pleura on both sides, ranging from 36% to 50% and 31% to 64% in rats receiving chrysotile and DHPN, respectively. Asbestos bodies were seen in the pleura on both sides and in the lung.}, } @article {pmid7181238, year = {1982}, author = {De Vuyst, P and Jedwab, J and Dumortier, P and Vandermoten, G and Vande Weyer, R and Yernault, JC}, title = {Asbestos bodies in bronchoalveolar lavage.}, journal = {The American review of respiratory disease}, volume = {126}, number = {6}, pages = {972-976}, doi = {10.1164/arrd.1982.126.6.972}, pmid = {7181238}, issn = {0003-0805}, mesh = {Adult ; Aged ; Asbestos/*isolation & purification ; Asbestosis/*diagnosis ; Bronchi/analysis/pathology ; Bronchoscopy ; Fiber Optic Technology/instrumentation ; Humans ; Male ; Middle Aged ; Pulmonary Alveoli/analysis/pathology ; Risk ; Therapeutic Irrigation ; }, abstract = {Asbestos bodies (AB) were counted in bronchoalveolar lavage (BAL) fluid from 62 patients with suspected asbestos related diseases, 2 patients with known exposure to asbestos but without related disease, and 40 control subjects. BAL fluid contained AB in all patients with obvious exposure (28 of 28), including the 2 without related disease, in most patients with suspected exposure (26 of 28), as well as in 5 of 8 patients without known exposure but with suspicion of asbestos related disease (mesothelioma or pleural plaques). Among the 40 control subjects, the results in 5 were positive but to a low degree (less than 1 AB/ml of fluid). Quantitative analysis correlated with the type of disease: AB counts were higher in patients with interstitial lung disease than in those with benign (p less than 0.02) or malignant (p less than 0.01) pleural disease. Only 9 of 13 patients with mesothelioma had a positive lavage. In conclusion, the finding of AB in BAL fluid correlates with the occupational risk and can disclose unknown exposure better than a questionnaire, but a positive lavage is not a proof of disease. Quantitative differences in AB counts suggest a different pathogenesis for pleural and parenchymal disease.}, } @article {pmid7139536, year = {1982}, author = {Roggli, VL and McGavran, MH and Subach, J and Sybers, HD and Greenberg, SD}, title = {Pulmonary asbestos body counts and electron probe analysis of asbestos body cores in patients with mesothelioma: a study of 25 cases.}, journal = {Cancer}, volume = {50}, number = {11}, pages = {2423-2432}, doi = {10.1002/1097-0142(19821201)50:11<2423::aid-cncr2820501130>3.0.co;2-i}, pmid = {7139536}, issn = {0008-543X}, mesh = {Adult ; Aged ; Asbestos/adverse effects/*analysis ; Electron Probe Microanalysis/methods ; Female ; Humans ; Male ; Mesothelioma/*etiology/ultrastructure ; Microscopy, Electron ; Middle Aged ; Peritoneal Neoplasms/etiology ; Pleural Neoplasms/etiology ; }, abstract = {Malignant mesotheliomas of the pleura and peritoneum are well-recognized risks of asbestos exposure. We determined the asbestos body content of the lungs from 24 cases of malignant mesothelioma (19 pleural, five peritoneal) and compared such to the content of lungs from 50 consecutive adult autopsies and four cases of overt asbestosis using a Clorox-digestion concentration technique. The cores of 90 asbestos bodies were examined by energy dispersive x-ray analysis and compared with similar data from 120 standard asbestos fibers and 20 fiberglass fibers. The malignant mesothelioma patients had asbestos body counts intermediate between those of the general population and those of patients with asbestosis, although some of the mesothelioma cases overlapped with the general population. These latter cases often lacked an identifiable occupational exposure to asbestos. EDXA studies demonstrated an amphibole core in 88 of the 90 asbestos bodies (amosite or crocidolite in 80 of 88, anthophyllite or tremolite in eight of 88), and chrysotile in two instances.}, } @article {pmid6762088, year = {1982}, author = {Ehrenreich, T and Espinosa, T and Langer, AM and Rohl, AN and Daum, SM}, title = {Asbestos-related diseases. Algorithm for forensic pathological diagnosis.}, journal = {The American journal of forensic medicine and pathology}, volume = {3}, number = {4}, pages = {315-321}, doi = {10.1097/00000433-198212000-00007}, pmid = {6762088}, issn = {0195-7910}, mesh = {Asbestos/*adverse effects/analysis ; Asbestosis/diagnosis ; Histological Techniques ; Humans ; Jurisprudence ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Occupational Diseases/*diagnosis/etiology ; }, abstract = {The pathological diagnosis and proof of asbestos causation in environmental-occupational diseases is based on a spectrum of increasingly sophisticated determinations with greater confidence in detection of asbestos bodies and fibers. These include the following: pathology (histology) and/or thick smears of lung, microincineration, bulk chemical digestion, and electron beam instruments. The requisites of medical and forensic asbestos causation differ, and do not always require the full range of these analytical techniques. The need and significance of some of these determinations, as expressed in number of asbestos bodies and fibers, may be related in many cases to the evidence of asbestosis; to the gross and microscopic pathological findings (asbestosis, lung carcinoma, mesothelioma); the exposure history (type, duration, intensity, and period of latency); and nature of the asbestos mineral. An algorithm for the forensic pathological diagnosis of asbestosis and of asbestos-related diseases is proposed.}, } @article {pmid6761970, year = {1982}, author = {Rom, WN and Lockey, JE}, title = {Diffuse malignant mesothelioma: a review.}, journal = {The Western journal of medicine}, volume = {137}, number = {6}, pages = {548-554}, pmid = {6761970}, issn = {0093-0415}, mesh = {Animals ; Asbestosis/*complications ; Humans ; Mesothelioma/diagnosis/*etiology ; Occupational Diseases/*etiology ; Occupations ; Pleural Neoplasms/diagnosis/*etiology ; Risk ; }, abstract = {Diffuse malignant mesothelioma is a signal tumor of asbestos exposure. Mesothelioma incidence has been steadily rising during the past two decades, reflecting the increases in asbestos use during and following World War II. The onset of the disease follows exposure by 25 to 40 years. The dose-response relationship appears to be much lower than that for asbestosis or lung cancer-it is not known whether current levels of exposure will entail a risk for disease 30 years hence. There is no synergistic or additive interaction with smoking for this tumor. Current knowledge indicates that pleural plaques, per se, do not increase the risk for this tumor beyond that of the previous asbestos exposure alone. Durable fibers with high aspect ratios, especially amphiboles, are associated with experimental tumor induction. Treatment modalities including surgical procedures and chemotherapy with doxorubicin and 5-azacytidine offer prospects for palliation.}, } @article {pmid6127563, year = {1982}, author = {Langer, AM and McCaughey, WT}, title = {Mesothelioma in a brake repair worker.}, journal = {Lancet (London, England)}, volume = {2}, number = {8307}, pages = {1101-1103}, doi = {10.1016/s0140-6736(82)90027-7}, pmid = {6127563}, issn = {0140-6736}, support = {ES00928/ES/NIEHS NIH HHS/United States ; }, mesh = {Asbestos/*adverse effects ; Asbestos, Serpentine ; *Automobiles ; Humans ; Male ; Mesothelioma/*etiology ; Middle Aged ; Occupational Diseases/*etiology ; Occupations ; Pleural Neoplasms/*etiology ; }, } @article {pmid7178029, year = {1982}, author = {Schlegel, H}, title = {[Danger to health from asbestos].}, journal = {Schweizerische Rundschau fur Medizin Praxis = Revue suisse de medecine Praxis}, volume = {71}, number = {45}, pages = {1763-1765}, pmid = {7178029}, issn = {1013-2058}, mesh = {Asbestos/*adverse effects ; Asbestosis/*etiology ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; Smoking ; }, } @article {pmid6291580, year = {1982}, author = {Acheson, ED and Gardner, MJ and Pippard, EC and Grime, LP}, title = {Mortality of two groups of women who manufactured gas masks from chrysotile and crocidolite asbestos: a 40-year follow-up.}, journal = {British journal of industrial medicine}, volume = {39}, number = {4}, pages = {344-348}, pmid = {6291580}, issn = {0007-1072}, mesh = {Asbestos/adverse effects ; Asbestos, Crocidolite ; Asbestos, Serpentine ; Asbestosis/*complications ; England ; Female ; Humans ; Lung Neoplasms/etiology/*mortality ; Mesothelioma/etiology/mortality ; Occupational Diseases/etiology/*mortality ; Ovarian Neoplasms/etiology/*mortality ; Respiratory Protective Devices ; Time Factors ; }, abstract = {Two groups of women were exposed to asbestos while manufacturing gas masks in Lancashire before and during the second world war. One group (in Blackburn) is believed to have been concerned almost exclusively with the manufacture of civilian respirators (containing chrysotile) while the other (in Leyland) made respirators for the armed Forces (containing crocidolite) and a much smaller number of civilian respirators. Excess mortality ascribed to lung cancer and ovarian cancer were found at the second factory (statistically significant at the 1% level) but not at the first. Mesothelioma was mentioned on the death certificates of five women who had worked in Leyland and one woman in Blackburn.}, } @article {pmid6897166, year = {1982}, author = {Craighead, JE and Abraham, JL and Churg, A and Green, FH and Kleinerman, J and Pratt, PC and Seemayer, TA and Vallyathan, V and Weill, H}, title = {The pathology of asbestos-associated diseases of the lungs and pleural cavities: diagnostic criteria and proposed grading schema. Report of the Pneumoconiosis Committee of the College of American Pathologists and the National Institute for Occupational Safety and Health.}, journal = {Archives of pathology & laboratory medicine}, volume = {106}, number = {11}, pages = {544-596}, pmid = {6897166}, issn = {0003-9985}, mesh = {Asbestos/*adverse effects ; Asbestosis/diagnosis/diagnostic imaging/*pathology/physiopathology ; Biopsy ; Humans ; Lung/diagnostic imaging/*pathology/physiopathology ; Lung Diseases/diagnosis/*pathology ; Lung Neoplasms/pathology ; Mesothelioma/pathology ; Peritoneal Neoplasms/pathology ; Pleura/*pathology ; Pleural Diseases/diagnosis/*pathology ; Pleural Neoplasms/pathology ; Radiography ; Sputum ; Therapeutic Irrigation ; }, } @article {pmid7158050, year = {1982}, author = {Schlegel, H and Kempf, E}, title = {[Mesothelioma following occupational contact with asbestos].}, journal = {Sozial- und Praventivmedizin}, volume = {27}, number = {5}, pages = {220-222}, pmid = {7158050}, issn = {0303-8408}, mesh = {Asbestos/*adverse effects ; Bronchial Neoplasms/etiology ; Humans ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; Pleural Neoplasms/etiology ; Registries ; Switzerland ; }, abstract = {From 1975 onwards, mesothelioma is by far the most often seen occupational tumour in Switzerland (about 70%). Between 1969 and 1982, there have been 49 cases registered by the SUVA (Schweizerische Unfallversicherungsanstalt, i.e. Swiss National Accident Insurance Fund). 10 together with asbestosis. Of the first 30 cases, the primary tumour only once was in the peritoneum, in all other cases the tumour always could be located in the pleura. The causative asbestos exposure was found in the production of asbestos cement (9), in the construction and reparation of waggons (6), in the insulation work at chemical plants (5) and in several other industrial work conditions (10). The average exposure time was 21 years. The average interval from exposure to diagnosis 35 years. The survival time after diagnosis about 1 year. Technical prevention consists in substitution of asbestos or elimination of respirable dust (or at least reduction below the TLV). Medical prevention: periodic fitness tests and follow up examinations. New cases should be communicated to the mesothelioma-register in Zurich and to the SUVA, for clarification of the industrial origin.}, } @article {pmid6980698, year = {1982}, author = {Dimitrov, NV and Egner, J and Balcueva, E and Suhrland, LG}, title = {High-dose methotrexate with citrovorum factor and vincristine in the treatment of malignant mesothelioma.}, journal = {Cancer}, volume = {50}, number = {7}, pages = {1245-1247}, doi = {10.1002/1097-0142(19821001)50:7<1245::aid-cncr2820500704>3.0.co;2-h}, pmid = {6980698}, issn = {0008-543X}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Drug Evaluation ; Drug Therapy, Combination ; Female ; Humans ; Leucovorin/administration & dosage ; Leukopenia/chemically induced ; Male ; Mesothelioma/*drug therapy/etiology/surgery ; Methotrexate/*administration & dosage/adverse effects ; Middle Aged ; Peritoneal Neoplasms/drug therapy ; Pleural Neoplasms/drug therapy ; Time Factors ; Vincristine/administration & dosage ; }, abstract = {The incidence of malignant mesothelioma has increased greatly in the last 40 years. Current and recent past exposure to asbestos is expected to substantially increase this incidence. We report nine cases of malignant mesothelioma which temporarily responded to treatment with high-dose methotrexate-citrovorum rescue and vincristine. Further clinical trials of high-dose methotrexate with citrovorum rescue appear indicated in this disease.}, } @article {pmid6291926, year = {1982}, author = {Kolev, K}, title = {Experimentally induced mesothelioma in white rats in response to intraperitoneal administration of amorphous crocidolite asbestos: preliminary report.}, journal = {Environmental research}, volume = {29}, number = {1}, pages = {123-133}, doi = {10.1016/0013-9351(82)90013-5}, pmid = {6291926}, issn = {0013-9351}, mesh = {Abdominal Neoplasms/*etiology/pathology ; Animals ; Asbestos/administration & dosage/*adverse effects ; Asbestos, Crocidolite ; Female ; Mesothelioma/*etiology/pathology ; Neoplasms, Experimental/chemically induced ; Particle Size ; Peritoneal Cavity ; Rats ; Rats, Inbred Strains ; }, } @article {pmid6297656, year = {1982}, author = {Wagner, JC and Berry, G and Pooley, FD}, title = {Mesotheliomas and asbestos type in asbestos textile workers: a study of lung contents.}, journal = {British medical journal (Clinical research ed.)}, volume = {285}, number = {6342}, pages = {603-606}, pmid = {6297656}, issn = {0267-0623}, mesh = {Aged ; Asbestos/adverse effects/*analysis ; Asbestos, Crocidolite ; Asbestos, Serpentine ; Female ; Humans ; Lung/*analysis ; Lung Neoplasms/*analysis/etiology ; Male ; Mesothelioma/*analysis/etiology ; Middle Aged ; Occupational Diseases/*pathology ; Pleural Neoplasms/etiology ; *Textile Industry ; }, abstract = {The asbestos contents of the lungs of former employees of an asbestos textile factory were determined at necropsy using a transmission electron microscope. Those who had died of mesothelioma were compared with a matched sample of those who had died of other causes. The predominant fibre processed in the factory was chrysotile, but crocidolite had also been used. The lung content was consistent with the known exposure to chrysotile, but the crocidolite content was also high, being about 300 times that of the general population of the United Kingdom. The lungs of those with mesothelioma did not contain more of either chrysotile or crocidolite than the lungs of the controls, so no particular type of asbestos could be implicated in causing the mesotheliomas. The evidence of substantial exposure to crocidolite means that the mesotheliomas that occurred in this factory could not be attributed with any certainty to the exposure to chrysotile.}, } @article {pmid7150478, year = {1982}, author = {Wagner, JC and Johnson, NF and Brown, DG and Wagner, MM}, title = {Histology and ultrastructure of serially transplanted rat mesotheliomas.}, journal = {British journal of cancer}, volume = {46}, number = {2}, pages = {294-299}, pmid = {7150478}, issn = {0007-0920}, mesh = {Animals ; Asbestos ; Cell Differentiation ; Female ; Male ; Mesothelioma/etiology/*pathology/ultrastructure ; Microscopy, Electron ; Neoplasm Transplantation ; Neoplasms, Experimental/pathology ; Pleural Neoplasms/etiology/*pathology/ultrastructure ; Rats ; }, } @article {pmid7093155, year = {1982}, author = {Thomas, HF and Benjamin, IT and Elwood, PC and Sweetnam, PM}, title = {Further follow-up study of workers from an asbestos cement factory.}, journal = {British journal of industrial medicine}, volume = {39}, number = {3}, pages = {273-276}, pmid = {7093155}, issn = {0007-1072}, mesh = {Asbestos/*adverse effects ; Female ; Follow-Up Studies ; Gastrointestinal Neoplasms/mortality ; Humans ; Lung Neoplasms/mortality ; Male ; Neoplasms/etiology/mortality ; Occupational Diseases/etiology/*mortality ; Pleural Neoplasms/mortality ; Wales ; }, abstract = {A further follow-up traced 1970 workers employed at an asbestos cement factory for at least six months between 1936 and 1977. At the beginning of this period some crocidolite was used in the factory but by the end of 1936 chrysotile had become the only type of asbestos in use. Only 378 women were employed during the period concerned, and of the 30 who had died, none had a cause of death that is generally associated with exposure to asbestos. The mortality experience of the men was examined separately for all workers, all workers alive after 15 or more years after first exposure, and a smaller group of workers who were employed in 1935-6 and may have been exposed to crocidolite. In none of the three groups was there an appreciably raised standardised mortality ratio (SMR) for the causes of death investigated. These were: all causes, all neoplasms, cancers of the lung and pleura, and cancers of the gastrointestinal tract. An excess of lung cancers noted in the first follow-up study in 1964 was not found in this study. Two pleural mesotheliomas were identified but in both cases the men had worked at the factory before 1936 and therefore had been exposed to crocidolite. No cancers of the larynx were found.}, } @article {pmid7049025, year = {1982}, author = {Becklake, MR}, title = {Asbestos-related diseases of the lungs and pleura: current clinical issues.}, journal = {The American review of respiratory disease}, volume = {126}, number = {2}, pages = {187-194}, doi = {10.1164/arrd.1982.126.2.187}, pmid = {7049025}, issn = {0003-0805}, mesh = {Asbestos/*adverse effects ; Asbestosis/etiology ; Bronchitis/etiology ; Dust/analysis ; Environmental Exposure ; Humans ; Lung/analysis ; Lung Diseases/*etiology ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Pleural Diseases/*etiology ; Pulmonary Fibrosis/etiology ; Risk ; }, } @article {pmid7083145, year = {1982}, author = {Cramer, DW and Welch, WR and Scully, RE and Wojciechowski, CA}, title = {Ovarian cancer and talc: a case-control study.}, journal = {Cancer}, volume = {50}, number = {2}, pages = {372-376}, doi = {10.1002/1097-0142(19820715)50:2<372::aid-cncr2820500235>3.0.co;2-s}, pmid = {7083145}, issn = {0008-543X}, support = {5-RO1 CA24209/CA/NCI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Boston ; Contraceptive Devices/adverse effects ; Female ; Humans ; Menopause ; Middle Aged ; Ovarian Neoplasms/epidemiology/*etiology ; Parity ; Pelvis/surgery ; Risk ; Talc/*adverse effects ; }, abstract = {Opportunities for genital exposure to talc were assessed in 215 white females with epithelial ovarian cancers and in 215 control women from the general population matched by age, race, and residence. Ninety-two (42.8%) cases regularly used talc either as a dusting powder on the perineum or on sanitary napkins compared with 61 (28.4%) controls. Adjusted for parity and menopausal status, this difference yielded a relative risk of 1.92 (P less than 0.003) for ovarian cancer associated with these practices. Women who had regularly engaged in both practices had an adjusted relative risk of 3.28 (P less than 0.001) compared to women with neither exposure. This provides some support for an association between talc and ovarian cancer hypothesized because of the similarity of ovarian cancer to mesotheliomas and the chemical relation of talc to asbestos, a known cause of mesotheliomas. The authors also investigated opportunities for potential talc exposure from rubber products such as condoms or diaphragms or from pelvic surgery. No significant differences were noted between cases and controls in these exposures, although the intensity of talc exposure from these sources was likely affected by variables not assessed in this study.}, } @article {pmid7088037, year = {1982}, author = {}, title = {Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 27-1982. Pleural thickening in a man with rheumatoid arthritis and exposure to asbestos.}, journal = {The New England journal of medicine}, volume = {307}, number = {2}, pages = {104-112}, doi = {10.1056/NEJM198207083070208}, pmid = {7088037}, issn = {0028-4793}, mesh = {Arthritis, Rheumatoid/*pathology ; Asbestosis/diagnosis/*pathology ; Diagnosis, Differential ; Humans ; Lung/pathology ; Lung Neoplasms/diagnosis ; Male ; Mesothelioma/diagnosis ; Middle Aged ; Pleura/pathology ; Pleurisy/diagnosis/*pathology ; Pulmonary Fibrosis/diagnosis/*pathology ; }, } @article {pmid7104200, year = {1982}, author = {Gardner, MJ and Acheson, ED and Winter, PD}, title = {Mortality from mesothelioma of the pleura during 1968-78 in England and Wales.}, journal = {British journal of cancer}, volume = {46}, number = {1}, pages = {81-88}, pmid = {7104200}, issn = {0007-0920}, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Asbestos/adverse effects ; England ; Female ; Humans ; Male ; Mesothelioma/etiology/*mortality ; Middle Aged ; Occupational Diseases/etiology/*mortality ; Pleural Neoplasms/etiology/*mortality ; Sex Factors ; Time Factors ; Wales ; }, abstract = {The geographical distribution of mortality from mesothelioma of the pleura during the years 1968-78 in England and Wales has been studied using extracts from the death records held by the Office of Population Censuses and Surveys. Using the national death rate as standard, Local Authority areas with raised mortality are identified. The patterns are somewhat different for each sex. In men the high-mortality areas are mainly the major ports where shipbuilding and repairing have been concentrated, whereas in women areas where gas masks are manufactured are predominant. In both sexes there are also high death rates on the eastern side of London. Nearly all the areas of high mortality are known to have had a major asbestos-using industry in the past. Over the 11-year period the annual number of deaths from pleural mesothelioma rose by approximately 75%. This marked increase was virtually confined to men, in whom the number of deaths had reached almost 200 per annum by 1978. The indications are that the effect of past high exposures, in particular to amphibole asbestos, have not yet reached a peak in terms of mortality. On the other hand imports and usage of amphiboles, particularly crocidolite, have decreased rapidly since the mid-1960s, and dust levels in the working environment have improved even more radically.}, } @article {pmid6294491, year = {1982}, author = {Rivolta, G and Todaro, A and Chiappino, G}, title = {[Carcinogenesis of mineral fibers: state of the art].}, journal = {La Medicina del lavoro}, volume = {73}, number = {4}, pages = {383-393}, pmid = {6294491}, issn = {0025-7818}, mesh = {Aluminum Silicates/adverse effects ; Animals ; Asbestos/adverse effects ; *Cocarcinogenesis ; Drug Synergism ; Environmental Exposure ; Epidemiologic Methods ; Glass ; Humans ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Minerals/*adverse effects ; Smoking ; Time Factors ; Zeolites ; }, } @article {pmid6290964, year = {1982}, author = {Henderson, DW}, title = {Asbestos-related pleuropulmonary diseases: asbestosis, mesothelioma and lung cancer.}, journal = {Pathology}, volume = {14}, number = {3}, pages = {239-243}, doi = {10.3109/00313028209061370}, pmid = {6290964}, issn = {0031-3025}, mesh = {Adenocarcinoma, Mucinous/analysis/pathology ; Asbestosis/*pathology ; Environmental Exposure ; Histocytochemistry ; Humans ; Lung Neoplasms/*pathology ; Mesothelioma/analysis/*pathology ; Pleural Neoplasms/*pathology ; Smoking ; Urban Population ; }, } @article {pmid7078593, year = {1982}, author = {Becklake, MR}, title = {Exposure to asbestos and human disease.}, journal = {The New England journal of medicine}, volume = {306}, number = {24}, pages = {1480-1482}, doi = {10.1056/NEJM198206173062409}, pmid = {7078593}, issn = {0028-4793}, mesh = {Asbestos/*adverse effects ; Asbestosis/etiology ; Environmental Pollutants/adverse effects ; Humans ; Mesothelioma/etiology ; Pleural Neoplasms/etiology ; }, } @article {pmid7043267, year = {1982}, author = {Craighead, JE and Mossman, BT}, title = {The pathogenesis of asbestos-associated diseases.}, journal = {The New England journal of medicine}, volume = {306}, number = {24}, pages = {1446-1455}, doi = {10.1056/NEJM198206173062403}, pmid = {7043267}, issn = {0028-4793}, mesh = {Air Pollution/analysis ; Asbestos/*adverse effects/analysis/metabolism ; Asbestosis/etiology ; Carcinoma, Bronchogenic/etiology ; Gastrointestinal Neoplasms/etiology ; Humans ; Lung/metabolism ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Microscopy, Electron, Scanning ; Occupational Medicine ; Peritoneal Neoplasms/etiology ; Pleural Diseases/etiology ; Pleural Neoplasms/etiology ; Smoking ; Water Pollution/analysis ; }, } @article {pmid7106077, year = {1982}, author = {Cole, DA and Stevens, RH and Will, LA}, title = {Identification of carcinogens by measurement of cell-mediated immunity. III. Immunity to asbestos-induced rat peritoneal mesothelioma.}, journal = {Environmental research}, volume = {28}, number = {1}, pages = {77-83}, doi = {10.1016/0013-9351(82)90155-4}, pmid = {7106077}, issn = {0013-9351}, support = {1R01-ESCA-02352-02/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; *Asbestos ; Cells, Cultured ; *Cytotoxicity, Immunologic ; Intestinal Neoplasms/immunology ; Lymphocytes/immunology ; Male ; Mesothelioma/etiology/*immunology ; Neoplasms, Experimental/etiology ; Pancreatic Neoplasms/immunology ; Peritoneal Neoplasms/etiology/*immunology ; Rats ; Rats, Inbred F344 ; }, } @article {pmid7106076, year = {1982}, author = {Stevens, RH and Cole, DA}, title = {Identification of carcinogens by measurements of cell-mediated immunity. II. Assay specificity.}, journal = {Environmental research}, volume = {28}, number = {1}, pages = {67-76}, doi = {10.1016/0013-9351(82)90154-2}, pmid = {7106076}, issn = {0013-9351}, support = {1R01-ESCA-02352-02/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Asbestos ; Carcinogens, Environmental/*pharmacology ; Colonic Neoplasms/immunology ; Cytotoxicity, Immunologic/*drug effects ; Intestinal Neoplasms/immunology ; Male ; Mesothelioma/immunology ; Neoplasms, Experimental/chemically induced/*immunology ; Neoplasms, Radiation-Induced/immunology ; Pancreatic Neoplasms/immunology ; Rats ; }, } @article {pmid7091938, year = {1982}, author = {Chahinian, AP and Pajak, TF and Holland, JF and Norton, L and Ambinder, RM and Mandel, EM}, title = {Diffuse malignant mesothelioma. Prospective evaluation of 69 patients.}, journal = {Annals of internal medicine}, volume = {96}, number = {6 Pt 1}, pages = {746-755}, doi = {10.7326/0003-4819-96-6-746}, pmid = {7091938}, issn = {0003-4819}, mesh = {Adult ; Aged ; Antineoplastic Agents/therapeutic use ; Asbestos/adverse effects ; Environmental Exposure ; Female ; Humans ; Male ; Mesothelioma/etiology/mortality/*pathology/therapy ; Middle Aged ; Peritoneal Neoplasms/pathology ; Pleural Neoplasms/pathology ; Prospective Studies ; }, abstract = {From 1974 to 1980, 69 patients with ith diffuse malignant mesothelioma were prospectively evaluated. The initial site of involvement was the pleura in 57 patients and the peritoneum in 12. Previous asbestos exposure was found in 53 patients (77%), with a shorter period of latency for peritoneal (mean, 28 years) than for ith pleural mesothelioma (mean, 35 years) than for pleural mesothelioma (mean, 35 years). Other associated exposure or diseases included talc, mica, familial Mediterranean fever, and diffuse lymphocytic lymphoma (one patient each). Thrombocytosis was common, as were thromboembolic episodes. Survival was significantly better for patients with an epithelial subtype, with pleural versus peritoneal mesothelioma, and for those under 65 years of age. Surgery was never curative, but its extent was correlated with survival and earlier diagnosis. Results of chemotherapy with doxorubicin and 5-azacytidine yielded a somewhat better survival rate than a combined program with doxorubicin and radiotherapy. Survival after chemotherapy was correlated with performance status, response to chemotherapy, and extent of previous surgery.}, } @article {pmid7074556, year = {1982}, author = {Brenner, J and Sordillo, PP and Magill, GB and Golbey, RB}, title = {Malignant mesothelioma of the pleura: review of 123 patients.}, journal = {Cancer}, volume = {49}, number = {11}, pages = {2431-2435}, doi = {10.1002/1097-0142(19820601)49:11<2431::aid-cncr2820491134>3.0.co;2-w}, pmid = {7074556}, issn = {0008-543X}, mesh = {Adolescent ; Female ; Humans ; Lymphatic Metastasis ; Male ; Mesothelioma/*diagnosis/pathology/surgery ; Middle Aged ; Neoplasm Metastasis ; Pleural Neoplasms/*diagnosis/pathology/surgery ; }, abstract = {One-hundred-twenty-three cases of malignant pleural mesothelioma were reviewed. Exposure to asbestos or to other industrial dusts or chemicals was an important etiologic factor with 24% of patients relating such a history. A history of prior irradiation or previous lung disease was also occasionally noted. Diagnosis was most often made by exploratory thoracotomy, with pleural biopsy or cytology rarely helpful. Except for nine patients, tumor was confined to the chest at the time of diagnosis, but in 33 of the remaining 114 patients, spread to the abdomen or distant metastasis was seen during the course of disease. Surgery and radiotherapy were ineffective in preventing local recurrence. There were only three major responses to chemotherapy in 111 trials. Median survival was 12 months, and only seven patients (5.6%) lived more than five years. Patients with epithelial mesothelioma and Stage I disease had the most favorable prognosis.}, } @article {pmid6291146, year = {1982}, author = {Boman, G and Schubert, V and Svane, B and Westerholm, P and Bolinder, E and Rohl, AN and Fischbein, A}, title = {Malignant mesothelioma in Turkish immigrants residing in Sweden.}, journal = {Scandinavian journal of work, environment & health}, volume = {8}, number = {2}, pages = {108-112}, doi = {10.5271/sjweh.2489}, pmid = {6291146}, issn = {0355-3140}, support = {ES-00928/ES/NIEHS NIH HHS/United States ; }, mesh = {Adult ; Aluminum Silicates/adverse effects ; Asbestos/adverse effects ; Humans ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Pleural Neoplasms/*epidemiology/etiology ; Sweden ; Turkey/ethnology ; Zeolites ; }, abstract = {Mesothelioma is a rare neoplasm in the general population, but it is strongly associated with previous asbestos exposure. The endemic occurrence of this disease in two villages in central Turkey has raised the question of whether the inhalation of naturally occurring zeolite dust may also be a factor in the development of mesothelioma. During the past few years a large portion of the inhabitants of one of the two villages of concern has immigrated to Sweden. This report presents three cases of malignant pleural mesothelioma and the results of a chest radiographic survey among these immigrants. Mineralogical analysis of lung tissue specimens from two of the cases revealed the presence of both zeolite and asbestos minerals and therefore suggested a synergistic effect involving both types of minerals. The importance of close medical surveillance of this high-risk population is emphasized, as is the possibility that similar cases appear in other countries because of increased migration.}, } @article {pmid6287988, year = {1982}, author = {Musk, AW and Woodward, SD}, title = {Conventional treatment and its effect on survival of malignant pleural mesothelioma in Western Australia.}, journal = {Australian and New Zealand journal of medicine}, volume = {12}, number = {3}, pages = {229-232}, doi = {10.1111/j.1445-5994.1982.tb02466.x}, pmid = {6287988}, issn = {0004-8291}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Asbestos, Crocidolite ; Australia ; Environmental Exposure ; Female ; Humans ; Male ; Mesothelioma/etiology/*mortality/therapy ; Middle Aged ; Pleural Neoplasms/etiology/*mortality/therapy ; Retrospective Studies ; Smoking ; }, abstract = {Analysis of the survival of all 81 cases of pathologically confirmed malignant pleural mesothelioma in Western Australia between January 1957 and December 1980 has revealed a median survival from diagnosis of 5.1 months (mean 7.8 months). The average time between presentation and diagnosis was 3.4 months. Survival was better in younger subjects and subjects selected for surgery but was unrelated to sex, symptoms at onset, history of asbestos exposure, tumour morphology, therapy other than surgery or year of presentation. The selection of subjects at earlier clinical stages for surgical intervention is considered to account for their longer survival. The outlook for patients with this disease remains poor and there is still no optimism for future advances in therapy.}, } @article {pmid6122981, year = {1982}, author = {}, title = {Mysterious pleural effusions.}, journal = {Lancet (London, England)}, volume = {1}, number = {8283}, pages = {1226}, pmid = {6122981}, issn = {0140-6736}, mesh = {Asbestos/adverse effects ; Diagnosis, Differential ; Humans ; Mesothelioma/diagnosis ; Pleural Effusion/diagnosis/*etiology ; Pleural Neoplasms/diagnosis ; }, } @article {pmid7077245, year = {1982}, author = {Gladfelter, T}, title = {Malignant mesothelioma: an occupation disease.}, journal = {The Journal of family practice}, volume = {14}, number = {5}, pages = {827, 830-2, 837, passim}, pmid = {7077245}, issn = {0094-3509}, mesh = {Asbestos/adverse effects ; Family Practice ; Humans ; Lung Neoplasms/*etiology/physiopathology ; Male ; Mesothelioma/*etiology/physiopathology ; Middle Aged ; Occupational Diseases/*etiology/physiopathology ; }, } @article {pmid6284070, year = {1982}, author = {Artvinli, M and Baris, YI}, title = {Environmental fiber-induced pleuro-pulmonary diseases in an Anatolian village: an epidemiologic study.}, journal = {Archives of environmental health}, volume = {37}, number = {3}, pages = {177-181}, doi = {10.1080/00039896.1982.10667559}, pmid = {6284070}, issn = {0003-9896}, mesh = {Adult ; Aged ; Aluminum Silicates/*poisoning ; Environmental Exposure ; Epidemiologic Methods ; Female ; Humans ; Lung Diseases/diagnostic imaging/*epidemiology/etiology ; Lung Neoplasms/diagnostic imaging/epidemiology/etiology ; Male ; Mesothelioma/diagnostic imaging/epidemiology/etiology ; Middle Aged ; Neoplasms/mortality ; Pleural Diseases/diagnostic imaging/*epidemiology/etiology ; Radiography ; Smoking ; Turkey ; Zeolites ; }, abstract = {This study was designed to determine the prevalence of pleural mesothelioma and other malignancies in the Anatolian village of Tuzköy, where neither asbestos nor any environmental carcinogen has been detected. Another village (Kizilköy) located 12 km from Tuzköy was selected as a control. Three hundred twelve subjects from Tuzköy who were at least 25 yr of age and 95 subjects from Kizilköy were studied. Analysis of X-rays of the Tuzköy group revealed that subjects had calcified pleural plaques (17%), pleural thickening (10.5%), obscured costophrenic angles (15%), and diffuse interstitial pulmonary fibrosis (12.1%). Sixty-seven deaths were records in Tuzköy during the previous 3 yr, 41 of which resulted from malignant diseases. There were no X-ray abnormalities or deaths resulting from malignancies in the control group. Because of the high incidence of mesothelioma and lung cancer which usually results from asbestos exposure, the presence of asbestos in Tuzköy was investigated, but none was detected in spite to Tuzköy's volcanic location. Nevertheless, zeolite, an asbestiform mineral, was detected in the stones of buildings and in the village soil, as well as in the lung and pleura of the patients during biopsy. Thus, this mineral was considered to be responsible for the fiber-induced pleuro-pulmonary diseases in Tuzköy. No zeolite was found in the soil and stones of the control village.}, } @article {pmid6280847, year = {1982}, author = {Rothschild, H and Buechner, H and Welsh, R and Vial, LJ and Weinberg, R}, title = {Histologic typing of lung cancer in Louisiana.}, journal = {Cancer}, volume = {49}, number = {9}, pages = {1874-1877}, doi = {10.1002/1097-0142(19820501)49:9<1874::aid-cncr2820490921>3.0.co;2-q}, pmid = {6280847}, issn = {0008-543X}, mesh = {Adenocarcinoma/mortality/*pathology ; Aged ; Carcinoma, Small Cell/mortality/*pathology ; Carcinoma, Squamous Cell/mortality/*pathology ; Female ; Humans ; Louisiana ; Lung Neoplasms/mortality/*pathology ; Male ; Middle Aged ; Retrospective Studies ; }, abstract = {To determine whether histologic patterns differed in the high- and low-lung cancer mortality parishes (counties) of Louisiana and whether the findings in the state differed from those in other parts of the United states, we studied the available histopathologic materials for 272 persons of the 815 who died of lung cancer in ten southern, nonurban Louisiana parishes during a seven-year period from 1971-1977. Squamous-cell carcinoma and small-cell anaplastic carcinoma were the most common tumor types, closely followed in frequency by adenocarcinoma, confirming reports by other investigators of a change during the past decade in the prevalence of various histopathologic types of lung cancer. The distribution of histopathologic types was not different for high- and low-mortality parishes but differed significantly from other areas of the U. S. Three persons had diagnoses consistent with pleural mesothelioma. Occupational histories obtained from relatives showed that one of those persons was a homemaker and the other two were sugarcane farmers with no discernable exposure to asbestos.}, } @article {pmid7071597, year = {1982}, author = {Rohl, AN and Langer, AM and Moncure, G and Selikoff, IJ and Fischbein, A}, title = {Endemic pleural disease associated with exposure to mixed fibrous dust in Turkey.}, journal = {Science (New York, N.Y.)}, volume = {216}, number = {4545}, pages = {518-520}, doi = {10.1126/science.7071597}, pmid = {7071597}, issn = {0036-8075}, mesh = {Dust ; Environmental Exposure ; Humans ; Lung Diseases/*chemically induced ; Lung Neoplasms/*chemically induced/epidemiology ; Mesothelioma/*chemically induced/epidemiology ; Turkey ; }, abstract = {Pleural mesothelioma, lung cancer, pleural calcification and fibrosis, and interstitial parenchymal fibrosis have been observed among inhabitants of several villages in south-central Turkey. Earlier reports have stated that environmental and lung tissue samples from this area contained the fibrous zeolite mineral erionite, and this mineral has generally been assumed to be the agent responsible for these endemic pathological conditions in the absence of asbestos outcroppings and usage. Several different kinds of asbestos minerals in addition to erionite have now been found in environmental samples taken from the villages where these diseases occur. The lung tissues of mesothelioma patients from these villages contain both fibrous zeolites and asbestos minerals.}, } @article {pmid7044686, year = {1982}, author = {Whitaker, D and Papadimitriou, JM and Walters, MN}, title = {The mesothelium and its reactions: a review.}, journal = {Critical reviews in toxicology}, volume = {10}, number = {2}, pages = {81-144}, doi = {10.3109/10408448209041321}, pmid = {7044686}, issn = {1040-8444}, mesh = {Biological Transport ; Cell Division ; Cells, Cultured ; Endothelium/cytology/immunology/metabolism/*physiology/ultrastructure ; Humans ; Inflammation/physiopathology ; Intercellular Junctions ; Mesothelioma/physiopathology ; Wound Healing ; }, abstract = {The origins, nature, and reactions of the mesothelium have intrigued investigators for over 100 years. Recently, the use of sophisticated techniques has clarified earlier impressions of its development, structure, and function. The structure of mesothelium reflects its functional properties, its long slender microvilli entrapping a layer of glycosoaminoglycans, providing a frictionless free surface between the parietal and visceral serosa. Transport requirements are met by various surface modifications and both inter- and intra-cellular mechanisms occur. The presence of stomatal openings in the mesothelial membrane has been established, and they may have a major role to play in the movement of cells to and from the serosal cavities. In addition, mesothelial cells can respond to situations of increased functional demand and during the course of inflammation, the mesothelium's fibrinolytic properties are of major importance in preventing the formation of adhesions and the enhancement of healing. Of all the unanswered questions the most significant is the nature, localization, and potentialities of mesothelial precursors. A mesodermal origin is readily acknowledged, but the healing process of damaged mesothelium is less clear. It seems probable that "mature" mesothelium is one source of cell renewal, but mesenchymal cells located in the submesothelial serosa are also strong contenders. Neoplastic mesothelium can adopt a spectrum of histological appearances, reflecting its mesodermal origins. In fact, overacceptance of this concept has erroneously led to the classification of other neoplasms arising in the serosal area as mesotheliomas. Although the ocogenic sequence is still obscure, asbestos is recognized as the major etiologic agent in malignant mesotheliomas. In 1955, Hartwell described differing impressions of the peritoneum as seen through the eyes of an anatomist, an histologist, and a surgeon. In this review on the mesothelium we have attempted to unravel some of its complexities as viewed by embryologists, electronmicroscopists, cell biologists, pathologists, and oncologists.}, } @article {pmid6281166, year = {1982}, author = {Churg, A}, title = {Fiber counting and analysis in the diagnosis of asbestos-related disease.}, journal = {Human pathology}, volume = {13}, number = {4}, pages = {381-392}, doi = {10.1016/s0046-8177(82)80227-x}, pmid = {6281166}, issn = {0046-8177}, support = {ES02117/ES/NIEHS NIH HHS/United States ; }, mesh = {Asbestos/*analysis ; Asbestos, Amphibole ; Asbestos, Crocidolite ; Asbestos, Serpentine ; Asbestosis/metabolism/*pathology ; Environmental Exposure ; Humans ; Lung/analysis/*ultrastructure ; Lung Neoplasms/ultrastructure ; Pleural Neoplasms/ultrastructure ; Silicon Dioxide/analysis ; }, abstract = {Analysis of numbers and types of asbestos fibers present in lung tissue may provide insights into the pathogenesis of asbestos-induced disease, as well as diagnostic information concerning the relationship of a given lesion to asbestos exposure. This type of analysis requires extraction of fibers and asbestos bodies from lung tissue, preferably by means of a digestion-and-concentration technique, and examination with a combination of electron optical techniques, including electron diffraction and energy-dispersive x-ray spectroscopy. The combination permits definitive identification of asbestos fibers. Asbestos bodies have been shown to contain asbestos no matter what population they are found in, but they appear to be of value in ascertaining unusual exposure only when present in very large numbers. Numbers of asbestos bodies markedly underestimate total numbers of fibers present in lung. In patients from the general population, the mean number of asbestos fibers is about 1 X 10(6)/g dry lung; of this number, more than 80 per cent are fibers of chrysotile less than 5 microns long. Patients in the general population who have pleural plaques have about the same total number of fibers, but their lungs contain about a 50-fold increase in long thin amphibole fibers of commercial origin. Patients who have asbestosis and most patients who have mesothelioma have 100 to 200 X 10(6) fibers/g dry lung; the grade of asbestosis appears to be related to total fiber content. Occasional patients may develop mesotheliomas with much smaller fiber burdens. Both benign and malignant pleural diseases appear to be closely related to the presence of long thin amphibole fibers. Analysis of pulmonary fiber burden suggest that asbestos-related disease is not merely a matter of total numbers of fibers present, but that factors such as fiber type and size are equally important.}, } @article {pmid7101223, year = {1982}, author = {Stovin, PG and Partridge, P}, title = {Pulmonary asbestos and dust content in East Anglia.}, journal = {Thorax}, volume = {37}, number = {3}, pages = {185-192}, pmid = {7101223}, issn = {0040-6376}, mesh = {Adenocarcinoma/pathology ; Adult ; Aged ; Asbestos/*analysis ; Carcinoma, Squamous Cell/pathology ; Dust/*analysis ; England ; Environmental Exposure ; Female ; Humans ; Lung/*chemistry/pathology ; Lung Diseases/*pathology ; Lung Neoplasms/*pathology ; Male ; Mesothelioma/*pathology ; Middle Aged ; }, abstract = {Measurements were made of the asbestos fibre and dust content of samples from 96 surgically excised lungs; 42 necropsies on patients with lung cancer, 11 necropsies on patients with non-pulmonary malignancies, and 59 necropsies on patients without any malignant disease. The patients' ages ranged from 45 to 74 years at the time of study. None of the patients had asbestosis. The distribution of fibres and dust content of the lungs showed a log-normal distribution. There was no significant difference in fibre counts or dust content between men and women, and between lung cancer and non-cancer patients. The only group with an association with a high asbestos fibre count was four necropsy cases of pleural mesothelioma. There was no significant relationship between asbestos fibre count and dust content of the lung. The present data suggest that asbestos fibre counts below 100,000 per gram of dried lung are not related to specific asbestos disease, although in the surgical cases who were closely questioned on their residential and occupational histories most of those with fibre counts above 30,000 per gram dried lung had had occasions of definite or very likely asbestos exposure.}, } @article {pmid6280741, year = {1982}, author = {Wagner, JC and Chamberlain, M and Brown, RC and Berry, G and Pooley, FD and Davies, R and Griffiths, DM}, title = {Biological effects of tremolite.}, journal = {British journal of cancer}, volume = {45}, number = {3}, pages = {352-360}, pmid = {6280741}, issn = {0007-0920}, mesh = {Animals ; *Asbestos, Amphibole ; Cell Line ; Cricetinae ; Cricetulus ; Dust ; Female ; Humans ; Lung Neoplasms/*etiology ; Macrophages/enzymology ; Male ; Mesothelioma/*etiology ; Mice ; Mutagenicity Tests ; Neoplasms, Experimental/etiology ; Particle Size ; Rats ; Rats, Inbred Strains ; Silicic Acid/*adverse effects ; Silicon Dioxide/*adverse effects ; }, abstract = {Tremolite is an amphibole which has been implicated in a variety of disease patterns in different parts of the world. It occurs in a number of phases, which are chemically identical but have specific physical characteristics. In an attempt to clarify the epidemiological findings, tremolite fibres of 3 specific forms--A, B and C--were characterized and studied for biological activity by: (i) in vivo intrapleural injection of rats (2 separate experiments--1 with poor survival). (ii) in vitro enzyme release from mouse peritoneal macrophages (iii) in vitro giant-cell formation in A549 cultures (iv) in vitro cytotoxicity for V79-4 cells. Sample C, which contained more long thin fibres than A and B, was alone in producing mesotheliomas. C, but not A or B, induced LDH and B-glucuronidase enzyme release, and induced giant cells. A was not cytotoxic, B moderately cytotoxic and C as highly cytotoxic as UICC crocidolite. The in vivo studies were marred by being split between 2 experiments, of which the second had poor survival. We are aware of the weakness of our in vivo data, but as Tremolite C was being considered for commercial use on the European market we felt it timely to submit our findings for publication.}, } @article {pmid7079703, year = {1982}, author = {Bignon, J and Brochard, P and Sebastien, P}, title = {[Asbestos pathology: clinical aspects epidemiological data and prevention].}, journal = {Schweizerische medizinische Wochenschrift}, volume = {112}, number = {6}, pages = {177-185}, pmid = {7079703}, issn = {0036-7672}, mesh = {Air Pollution ; Asbestosis/complications/*pathology ; Carcinogens ; France ; Humans ; Iron/adverse effects ; Legislation as Topic ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; }, abstract = {The word "asbestos" is used to designate the main commercial types of asbestos (chrysotile, crocidolite, amosite) but there exist numerous asbestiform fibrous minerals, which are commercially valueless but widespread at the surface of the earth. Among them zeolite has already created health hazards in Turkey. Measurement of fibres in air and in tissues can contribute to a better knowledge of lung and body fibre burden associated with diseases. Among fibre-related diseases, studies have recently focused on clinical, epidemiological and pathogenic aspects of pleural fibrosis and lung or pleural cancer. At present the roles of the different types of fibres in the genesis of these diseases remain controverted. However, tobacco smoke associated with inhaled asbestos fibres provokes a multiplied risk of lung cancer. Regarding asbestos there exist regulations in most industrial countries designed to protect workers and diminish environmental pollution.}, } @article {pmid7054563, year = {1982}, author = {Epler, GR and McLoud, TC and Gaensler, EA}, title = {Prevalence and incidence of benign asbestos pleural effusion in a working population.}, journal = {JAMA}, volume = {247}, number = {5}, pages = {617-622}, pmid = {7054563}, issn = {0098-7484}, support = {HL 1173/HL/NHLBI NIH HHS/United States ; HL 19717/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; Asbestos/*adverse effects ; Dose-Response Relationship, Drug ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Occupational Diseases/*epidemiology/etiology ; Occupations ; Pleural Effusion/diagnostic imaging/*epidemiology/etiology ; Radiography ; Time Factors ; }, abstract = {Benign asbestos effusion was defined by (1) exposure to asbestos, (2) confirmation by roentgenograms or thoracenteses, (3) no other disease related to pleural effusion, and (4) no malignant tumor within three years. There were 34 benign effusions among 1,135 exposed workers compared with no otherwise unexplained effusions among 717 control subjects. Prevalence was dose related with 7.0%, 3.7%, and 0.2% effusions with severe (III), indirect (II), and peripheral (I) exposure, respectively. The latency period was shorter than for other asbestos-related disorders. Benign effusion was the most common asbestos-related abnormality during the first 20 years after exposure. Incidence studies showed 9.2 effusions per 1,000 person-years for level III exposure, 3.9 for level II, and 0.7 for level I. Most effusions were small; 28.6% recurred, and 66% were asymptomatic. There was one mesothelioma six years after effusion. Asbestos exposure should be carefully searched for in patients with "idiopathic" pleural effusion.}, } @article {pmid7068247, year = {1982}, author = {}, title = {Criteria for the diagnosis of asbestosis and considerations in the attribution of lung cancer and mesothelioma to asbestos exposure. Prepared by the Medical Advisory Panel to the Asbestos International Association.}, journal = {International archives of occupational and environmental health}, volume = {49}, number = {3-4}, pages = {357-361}, doi = {10.1007/BF00377945}, pmid = {7068247}, issn = {0340-0131}, mesh = {Asbestos ; Asbestosis/*diagnosis/etiology ; Environmental Exposure ; Humans ; Lung Neoplasms/*diagnosis/etiology ; Male ; Mesothelioma/*diagnosis/etiology ; }, } @article {pmid7066222, year = {1982}, author = {Morgan, A and Holmes, A}, title = {Concentrations and characteristics of amphibole fibres in the lungs of workers exposed to crocidolite in the British gas-mask factories, and elsewhere, during the second world war.}, journal = {British journal of industrial medicine}, volume = {39}, number = {1}, pages = {62-69}, pmid = {7066222}, issn = {0007-1072}, mesh = {Aged ; Asbestos/adverse effects/*analysis ; Australia ; England ; Female ; Humans ; Lung/*analysis/ultrastructure ; Male ; Mesothelioma/etiology ; Microscopy, Electron ; Middle Aged ; Mining ; Occupational Diseases/etiology ; Particle Size ; *Protective Devices ; *Respiratory Protective Devices ; }, abstract = {Concentrations and length distributions of uncoated and coated amphibole fibres in the lungs of 27 workers at the Leyland, Nottingham, and Blackburn gas-mask factories were measured after death with the light microscope using the membrane filter technique. Measurements were also made on a worker exposed to crocidolite at the Chemical Defence Experimental Establishment, Porton, and on three miners from the Wittenoom mine in Western Australia where the crocidolite used in the manufacture of military respirators is reputed to have originated. In selected cases, fibre concentrations and dimensions were also measured with the electron microscope. All but two subjects died with a mesothelial tumour. Fibre concentrations ranged from 7 x 10(4) to almost 10(9) fibres/g dry weight. There appeared to be no relation between latent period and fibre concentration. The significance of the wide range of fibre concentrations which was associated with the development of mesothelial tumours is discussed and also the relation between the relative frequency and dimensions of uncoated and coated fibres.}, } @article {pmid7066220, year = {1982}, author = {McMillan, GH and Rossiter, CE}, title = {Development of radiological and clinical evidence of parenchymal fibrosis in men with non-malignant asbestos-related pleural lesions.}, journal = {British journal of industrial medicine}, volume = {39}, number = {1}, pages = {54-59}, pmid = {7066220}, issn = {0007-1072}, mesh = {Asbestos/*adverse effects ; Asbestosis/diagnostic imaging/*etiology ; England ; Follow-Up Studies ; Humans ; Male ; Occupational Diseases/*complications/diagnostic imaging/etiology ; Pleural Diseases/*complications/diagnostic imaging/etiology ; Radiography ; Smoking ; }, abstract = {After assessment of radiographs taken in 1966, 201 men employed at HM Dockyard, Devonport, were judged to have pleural abnormalities due to exposure to asbestos but to be free from small opacities (ILO U/C 1971 category 1/1 or more), mesothelioma, or bronchial carcinoma. By 1976, 32 of these men had died. Of the survivors, 155 were re-examined to determine the attack rates of parenchymal fibrosis or malignant disease, or both. In 1976, 16 (10.3%) of the survivors had radiographs showing small opacities of category 1/1 or more. When additional clinical criteria had to be satisfied before a diagnosis of parenchymal fibrosis was made the attack rate in the survivors was 4.5%. These attack rates were substantially higher than those observed in a sample of men with no initial pleural abnormality but were unrelated to age, smoking habit, occupation, duration of exposure to asbestos, or type of pleural abnormality. The number of cases of malignant disease was too small to allow any reliable conclusions.}, } @article {pmid7066218, year = {1982}, author = {Wignall, BK and Fox, AJ}, title = {Mortality of female gas mask assemblers.}, journal = {British journal of industrial medicine}, volume = {39}, number = {1}, pages = {34-38}, pmid = {7066218}, issn = {0007-1072}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; England ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/etiology/mortality ; Mesothelioma/etiology/mortality ; Middle Aged ; Neoplasms/etiology/*mortality ; Occupational Diseases/etiology/*mortality ; Prospective Studies ; *Protective Devices ; *Respiratory Protective Devices ; }, abstract = {A 30-year follow-up study of the mortality of 500 women employed in manufacturing gas masks during the second world war showed a pronounced excess of deaths from mesothelioma and lung cancer. Although these women were subject only to short periods of exposure, greater excesses were found for those exposed for between one and five years than for those exposed for under one year. Even in the latter group, however, five deaths from lung cancer and four deaths from mesothelioma were recorded compared with 1.5 deaths and 0.1 deaths expected (p approximately equal to 0.02). An excess of deaths from cancer of the ovary was also found, and this appeared to be related to exposure to asbestos.}, } @article {pmid6952073, year = {1982}, author = {Jackson, DV and Marshall, RB and Albertson, DA and Slatkoff, ML}, title = {Malignant pleural mesothelioma: difficulties in diagnosis.}, journal = {North Carolina medical journal}, volume = {43}, number = {2}, pages = {118-119}, pmid = {6952073}, issn = {0029-2559}, support = {CA 2472001A1/CA/NCI NIH HHS/United States ; }, mesh = {Asbestos/adverse effects ; Humans ; Lung Neoplasms/*diagnosis/ultrastructure ; Male ; Mesothelioma/*diagnosis/etiology/ultrastructure ; Middle Aged ; }, } @article {pmid7181279, year = {1982}, author = {Wagner, JC and Pooley, FD and Berry, G and Seal, RM and Munday, DE and Morgan, J and Clark, NJ}, title = {A pathological and mineralogical study of asbestos-related deaths in the United Kingdom in 1977.}, journal = {The Annals of occupational hygiene}, volume = {26}, number = {1-4}, pages = {423-431}, pmid = {7181279}, issn = {0003-4878}, mesh = {Asbestos/*analysis ; Asbestosis/*metabolism ; Humans ; Lung/*analysis ; Lung Neoplasms/*analysis ; Mesothelioma/*analysis ; }, } @article {pmid7171091, year = {1982}, author = {Goldsmith, JR}, title = {Asbestos as a systemic carcinogen: the evidence from eleven cohorts.}, journal = {American journal of industrial medicine}, volume = {3}, number = {3}, pages = {341-348}, doi = {10.1002/ajim.4700030309}, pmid = {7171091}, issn = {0271-3586}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Female ; Humans ; Male ; Middle Aged ; Neoplasms/*chemically induced/immunology ; Occupational Diseases/*chemically induced ; }, abstract = {Most known occupational carcinogens are site-specific, which implies that they are "complete" carcinogens with both "initiating" and "promoting" properties (Berenblum's terminology). Excess cancer at gastrointestinal sites among cohorts occupationally exposed to asbestos has been interpreted as reflecting additional site-specific effects, although excess at other sites has also been observed in some studies. The hypothesis that excess cancer at gastrointestinal sites cannot be distinguished from excess cancer at all nonpulmonary sites is tested by data from New York-New Jersey insulation workers working in 1943; similar workers employed after 1943; U.S.-Canadian insulation workers; London factory workers, male and female; Quebec miners and millers; retired U.S. factory workers; U.S. shipyard insulators; Italian shipyard workers in Genoa; Amosite factory workers; and U.S. factory workers. Excluding lung cancer and mesothelioma, observed-expected ratios for nonpulmonary cancer mortality range from 0.97 to 2.78, and do not differ significantly from gastrointestinal ratios. A dose-response gradient is observed for both ratios, when dose is estimated from lung cancer ratios, or in some studies, measured exposures. Site-specificity is unlikely for nonpulmonary cancer associated with asbestos exposure more than 20 years previously. Systemic carcinogenesis may be an example of promotion or impairment by asbestos of some cancer defense mechanism; immunological mechanisms have been suggested by Turner-Warwick and Parkes. Prospective studies are indicated.}, } @article {pmid7171087, year = {1982}, author = {Nicholson, WJ and Perkel, G and Selikoff, IJ}, title = {Occupational exposure to asbestos: population at risk and projected mortality--1980-2030.}, journal = {American journal of industrial medicine}, volume = {3}, number = {3}, pages = {259-311}, doi = {10.1002/ajim.4700030305}, pmid = {7171087}, issn = {0271-3586}, support = {ES00928/ES/NIEHS NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Asbestos/*adverse effects ; Humans ; Intestinal Neoplasms/mortality ; Lung Neoplasms/epidemiology/etiology/*mortality ; Male ; Mesothelioma/epidemiology/mortality ; Middle Aged ; Occupational Diseases/epidemiology/*mortality ; Risk ; Time Factors ; United States ; }, abstract = {Estimates have been made of the numbers of cancers that are projected to result from past exposures to asbestos in a number of occupations and industries. From 1940 through 1979, 27,500,000 individuals had potential asbestos exposure at work. Of these, 18,800,000 had exposure in excess of that equivalent to two months employment in primary manufacturing or as an insulator (greater than 2-3 f-yr/ml). 21,000,000 of the 27,500,000 and 14,100,000 of the 18,800,000 are estimated to have been alive on January 1, 1980. It is further estimated that approximately 8,200 asbestos-related cancer deaths are now occurring annually. This will rise to about 9,700 annually by the year 2000. Thereafter, the mortality rate from past exposure will decrease, but still remain substantial for another three decades.}, } @article {pmid7171067, year = {1982}, author = {Dobiás, J}, title = {Pathology of pulmonary asbestosis in asbestos--exposed industrial workers in the Czech Socialist Republic.}, journal = {Acta Universitatis Carolinae. Medica}, volume = {28}, number = {3-4}, pages = {169-236}, pmid = {7171067}, issn = {0001-7116}, mesh = {Adult ; Aged ; Animals ; Asbestos/adverse effects ; Asbestosis/complications/epidemiology/etiology/*pathology ; Czechoslovakia ; Female ; Humans ; Lung/*pathology ; Lung Neoplasms/complications/pathology ; Male ; Mesothelioma/complications/pathology ; Middle Aged ; Pleura/pathology ; Pulmonary Fibrosis/etiology ; }, } @article {pmid7168449, year = {1982}, author = {Hirsch, A and Brochard, P and De Cremoux, H and Erkan, L and Sebastien, P and Di Menza, L and Bignon, J}, title = {Features of asbestos-exposed and unexposed mesothelioma.}, journal = {American journal of industrial medicine}, volume = {3}, number = {4}, pages = {413-422}, doi = {10.1002/ajim.4700030407}, pmid = {7168449}, issn = {0271-3586}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Epidemiologic Methods ; Female ; France ; Humans ; Male ; Mesothelioma/diagnosis/*etiology ; Middle Aged ; Peritoneal Neoplasms/diagnosis/*etiology ; Pleural Neoplasms/diagnosis/*etiology ; Probability ; }, abstract = {Thirty-six histologically confirmed cases of pleural and peritoneal mesothelioma have been observed in a chest unit over a period of 53 months. The past asbestos exposure was assessed by a standardized questionnaire in all cases and the asbestos lung burden was determined by means of mineralogical analysis of lung-related biological specimens (sputum, bronchoalveolar lavage fluid, lung tissues) in 28 cases. The results of these two methods were found in good agreement. Past asbestos exposure has been definitely implicated in 17 cases and definitely eliminated in 10 cases. The results were inconclusive in other cases. The group with definite past asbestos exposure was different from the nonasbestos-exposed group by clinical, biological, pathological, and prognosis features that were analyzed. In cases without past asbestos exposure there were no other possible causative agents. Younger age and similar incidence in men and women suggest an environmental or natural disease.}, } @article {pmid7137171, year = {1982}, author = {Beck, B and Konetzke, G and Ludwig, V and Röthig, W and Sturm, W}, title = {Malignant pericardial mesotheliomas and asbestos exposure: a case report.}, journal = {American journal of industrial medicine}, volume = {3}, number = {2}, pages = {149-159}, doi = {10.1002/ajim.4700030205}, pmid = {7137171}, issn = {0271-3586}, mesh = {Aged ; Asbestos/*adverse effects ; Heart Neoplasms/*etiology/pathology ; Humans ; Male ; Mesothelioma/*etiology/pathology ; Middle Aged ; Occupational Diseases/*etiology/pathology ; *Pericardium ; }, abstract = {Three cases of malignant pericardial mesotheliomas are presented with evidence of occupational asbestos exposure. Examination results are compared with findings from experimental and epidemiological research on biological effects of asbestos dust. There are sufficient indications that time-limited effects of asbestos dust established either by measurements or assessment of the amount of concentration after a latency of more than 20 years are apt to result in the development of mesotheliomas of the pleura and peritoneum and, moreover, the pericardium. It is suggested that malignant pericardial mesothelioma also be recognized as another form of occupational disease caused by asbestos dust.}, } @article {pmid7100857, year = {1982}, author = {McDonald, AD and Fry, JS}, title = {Mesothelioma and the fiber type in three American asbestos factories - preliminary report.}, journal = {Scandinavian journal of work, environment & health}, volume = {8 Suppl 1}, number = {}, pages = {53-58}, pmid = {7100857}, issn = {0355-3140}, mesh = {Asbestos/*adverse effects ; Death Certificates ; Epidemiologic Methods ; Female ; Humans ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; Occupational Diseases/etiology/*mortality ; United States ; }, abstract = {Preliminary findings are reported from three cohort studies in two asbestos factories (A and B) where chrysotile only was processed and a third (C) where chrysotile, amosite, and crocidolite were used. A total of 10,763 men and 3,118 women has been studied, of whom 97% and 89%, respectively, have been traced and 36% and 16% have died. Death certificates have so far been obtained and coded for 89% of the deaths. The standardized mortality ratios (SMRs) for persons employed less than a year varied greatly between plants. For men employed at least 1 a, an SMR of 129 for all causes and one of 285 for respiratory cancer were found in the chrysotile textile plant (A). The experience of respiratory cancer in this textile plant appears much worse in relation to fiber exposure levels than that observed in chrysotile mines and mills. Other findings in the three plants await clarification by analyses of exposure-response relationships. Among 2,341 deaths from the two chrysotile factories there has been one mesothelioma (0.4 per 1,000); among 1,429 deaths at factory C, which used mixed fibers, there have been 18 (12.6 per 1,000). This finding supports much other evidence that amphiboles are mainly responsible for mesothelioma, whereas chrysotile has little or no mesothelioma-producing potential.}, } @article {pmid7059455, year = {1982}, author = {Peto, J and Seidman, H and Selikoff, IJ}, title = {Mesothelioma mortality in asbestos workers: implications for models of carcinogenesis and risk assessment.}, journal = {British journal of cancer}, volume = {45}, number = {1}, pages = {124-135}, pmid = {7059455}, issn = {0007-0920}, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Asbestos/*adverse effects ; Humans ; Male ; Mesothelioma/etiology/*mortality ; Middle Aged ; *Models, Biological ; North America ; Occupational Diseases/etiology/*mortality ; Peritoneal Neoplasms/etiology/*mortality ; Pleural Neoplasms/etiology/*mortality ; Risk ; Time Factors ; }, abstract = {Mesothelioma death rates in asbestos workers appear to be proportional to the 3rd or 4th power of time from first exposure under a wide range of conditions of exposure for both pleural and peritoneal tumours, though the peritoneal:pleural ratio depends on fibre dimension and type. Age at first exposure has little or no influence, however, which supports the "multi-stage" model of carcinogenesis under which the increase in most cancer incidence rates with age is due to a constant incidence of genetic or epigenetic accidents, rather than to progressive generalized changes in regulatory or immune function. These relationships provide a simple basis for risk assessment, and support the suggestion that mesotheliomas may constitute a high proportion of cancer deaths resulting from early exposure to asbestos.}, } @article {pmid7053810, year = {1982}, author = {Japko, L and Horta, AA and Schreiber, K and Mitsudo, S and Karwa, GL and Singh, G and Koss, LG}, title = {Malignant mesothelioma of the tunica vaginalis testis: report of first case with preoperative diagnosis.}, journal = {Cancer}, volume = {49}, number = {1}, pages = {119-127}, doi = {10.1002/1097-0142(19820101)49:1<119::aid-cncr2820490123>3.0.co;2-u}, pmid = {7053810}, issn = {0008-543X}, support = {5 RO1 CA-27081-02/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Antigens, Neoplasm/analysis ; Biopsy, Needle ; Desmosomes/ultrastructure ; Humans ; Male ; Mesothelioma/etiology/*pathology/ultrastructure ; Microscopy, Electron ; Microvilli/ultrastructure ; Testicular Hydrocele/immunology/*pathology ; Testicular Neoplasms/etiology/*pathology ; }, abstract = {The cytologic, histologic and ultrastructural features of a malignant carcinomatous mesothelioma of the tunica vaginalis testis in a 30-year old patient are described. This is the first such case with preoperative diagnosis by cytologic examination of hydrocele fluid and the second with documented history of exposure to asbestos. The identity of the tumor was confirmed by a positive immunoperoxidase reaction directed against mesothelial cells. A review of the previously described ten cases is presented.}, } @article {pmid6962080, year = {1982}, author = {Huuskonen, MS}, title = {Asbestos and cancer.}, journal = {European journal of respiratory diseases. Supplement}, volume = {123}, number = {}, pages = {145-152}, pmid = {6962080}, issn = {0106-4347}, mesh = {*Asbestosis ; Dose-Response Relationship, Drug ; Gastrointestinal Neoplasms/etiology ; Humans ; Laryngeal Neoplasms/etiology ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Neoplasms/*etiology ; Smoking ; Time Factors ; }, } @article {pmid6953786, year = {1982}, author = {Seidman, H and Selikoff, IJ and Hammond, EC}, title = {Mortality of brain tumors among asbestos insulation workers in the United States and Canada.}, journal = {Annals of the New York Academy of Sciences}, volume = {381}, number = {}, pages = {160-171}, doi = {10.1111/j.1749-6632.1982.tb50380.x}, pmid = {6953786}, issn = {0077-8923}, support = {ES 00928/ES/NIEHS NIH HHS/United States ; }, mesh = {Adult ; Aged ; *Asbestos ; Brain Neoplasms/etiology/*mortality ; Canada ; Dust ; Humans ; *Industry ; Male ; Middle Aged ; Occupational Diseases/etiology/*mortality ; United States ; }, abstract = {Death resulting from brain tumors among workers in the petrochemical industry have called attention to the possibility that these neoplasms may be the result of occupational exposure to carcinogens. We have examined the experience of a cohort of 17,800 insulation workers known to be at significant increased risk of cancer at a number of sites (lung, mesothelioma, gastrointestinal, oral cavity, pharyngeal, larynx, renal) to ascertain whether their asbestos exposure also increased their risk of brain tumors. From 1967 to 1979, there were 24 deaths from primary brain tumors in this cohort, somewhat more than were anticipated (18.0 such deaths were expected based on U.S. general population data, and 20.5 if smoking was taken into account). The excess was not "statistically significant" at the 5% level although this does not rule out the possibility of an etiological association. It was of interest that the observed excess was concentrated (about twice expected) among insulators in the younger ages (those under 50) and during the early period after onset of work (15-24 years), in contrast with age distribution and latency in other asbestos-associated neoplasms. This may have relevance to theoretical concerns about questions of initiation and promotion in the etiology of cancer, particularly with regard to brain tumors.}, } @article {pmid6304601, year = {1982}, author = {Churg, A and Golden, J}, title = {Current problems in the pathology of asbestos--related disease.}, journal = {Pathology annual}, volume = {17 Pt 2}, number = {}, pages = {33-66}, pmid = {6304601}, issn = {0079-0184}, support = {ES02117/ES/NIEHS NIH HHS/United States ; }, mesh = {Asbestos/*adverse effects/analysis ; Asbestosis/*pathology ; Carcinoma, Small Cell/pathology ; Carcinoma, Squamous Cell/pathology ; Female ; Humans ; Lung Neoplasms/etiology/*pathology ; Male ; Mesothelioma/etiology/pathology ; Pleural Diseases/etiology/*pathology ; }, } @article {pmid6295251, year = {1982}, author = {Newhouse, ML and Berry, G and Skidmore, JW}, title = {A mortality study of workers manufacturing friction materials with chrysotile asbestos.}, journal = {The Annals of occupational hygiene}, volume = {26}, number = {1-4}, pages = {899-909}, pmid = {6295251}, issn = {0003-4878}, mesh = {Aged ; Asbestos/*adverse effects ; Asbestos, Serpentine ; Female ; Humans ; Male ; Mesothelioma/mortality ; Middle Aged ; *Mortality ; Neoplasms/mortality ; Occupational Diseases/etiology/*mortality ; Pleural Neoplasms/mortality ; }, } @article {pmid6295247, year = {1982}, author = {Bolton, RE and Davis, JM and Donaldson, K and Wright, A}, title = {Variations in the carcinogenicity of mineral fibres.}, journal = {The Annals of occupational hygiene}, volume = {26}, number = {1-4}, pages = {569-582}, pmid = {6295247}, issn = {0003-4878}, mesh = {Animals ; Asbestos/*adverse effects ; Asbestos, Amosite ; Asbestos, Serpentine ; Dust/*adverse effects ; Male ; Mesothelioma/*etiology ; Neoplasms, Experimental/etiology ; Peritoneal Neoplasms/*etiology ; Rats ; Rats, Inbred Strains ; }, } @article {pmid6295245, year = {1982}, author = {McDonald, AD and McDonald, JC and Pooley, FD}, title = {Mineral fibre content of lung in mesothelial tumours in North America.}, journal = {The Annals of occupational hygiene}, volume = {26}, number = {1-4}, pages = {417-422}, pmid = {6295245}, issn = {0003-4878}, mesh = {Asbestos/*analysis ; Asbestos, Serpentine ; Female ; Humans ; Lung/*analysis ; Male ; Mesothelioma/*analysis ; Minerals/*analysis ; Occupational Diseases/metabolism ; Peritoneal Neoplasms/analysis ; Pleural Neoplasms/analysis ; }, } @article {pmid6118770, year = {1981}, author = {Acheson, ED and Bennett, C and Gardner, MJ and Winter, PD}, title = {Mesothelioma in a factory using amosite and chrysotile asbestos.}, journal = {Lancet (London, England)}, volume = {2}, number = {8260-61}, pages = {1403-1406}, doi = {10.1016/s0140-6736(81)92813-0}, pmid = {6118770}, issn = {0140-6736}, mesh = {Adult ; Asbestos/*adverse effects ; Asbestos, Amosite ; Asbestos, Serpentine ; Humans ; Male ; Mesothelioma/*etiology/mortality ; Middle Aged ; Peritoneal Neoplasms/*etiology/mortality ; Pleural Neoplasms/*etiology/mortality ; Time Factors ; }, } @article {pmid6118766, year = {1981}, author = {}, title = {Amosite asbestos and mesothelioma.}, journal = {Lancet (London, England)}, volume = {2}, number = {8260-61}, pages = {1397-1398}, pmid = {6118766}, issn = {0140-6736}, mesh = {Animals ; Asbestos/*adverse effects ; Asbestos, Amosite ; Asbestos, Serpentine ; Humans ; Male ; Mesothelioma/*etiology/mortality ; Peritoneal Neoplasms/*etiology ; Pleural Neoplasms/*etiology ; }, } @article {pmid7336367, year = {1981}, author = {Robinson, BW and Musk, AW}, title = {Benign asbestos pleural effusion: diagnosis and course.}, journal = {Thorax}, volume = {36}, number = {12}, pages = {896-900}, pmid = {7336367}, issn = {0040-6376}, mesh = {Asbestos/*adverse effects ; Humans ; Male ; Middle Aged ; Occupational Diseases/diagnosis/*etiology ; Pleural Effusion/diagnosis/*etiology ; Prognosis ; Retrospective Studies ; }, abstract = {We have reviewed 22 patients with benign asbestos pleural effusion seen over a 17-year period. The mean duration of exposure to asbestos was 5.5 years and the mean interval between exposure and presentation was 16.3 years. In five the effusion was asymptomatic. Fever was uncommon but in 15 of 21 patients the ESR was elevated. Leucocytosis was noted in seven of 20 patients. Autoantibodies were rarely detected. The pleural fluid was usually blood-stained and the volume aspirated was rarely larger than 500 ml. Pleural biopsies revealed established pleural fibrosis and/or inflammatory infiltration with fibrinous exudate and mesothelial and fibroblastic proliferation. A positive mantoux test was noted in eight of 12 patients but there was no other evidence of tuberculosis. The mean duration to spontaneous resolution of the effusion was 4.3 months. During a follow-up period of 28.1 years from initial exposure to asbestos (mean 22.8 years) and up to 17.2 years from initial presentation with a pleural effusion (mean 6.3 years) seven patients had a single recurrence and only one patient had multiple pleural effusions. Only three patients experienced persistent pleural pain. It was not possible to predict the likelihood of recurrence of an effusion or the persistence of pleural pain from the data at presentation. No patient subsequently developed mesothelioma or other neoplasm.}, } @article {pmid6947851, year = {1981}, author = {Selikoff, IJ}, title = {Household risks with inorganic fibers.}, journal = {Bulletin of the New York Academy of Medicine}, volume = {57}, number = {10}, pages = {947-961}, pmid = {6947851}, issn = {0028-7091}, mesh = {Adult ; Age Factors ; *Asbestos ; Asbestosis/complications/etiology ; *Environmental Pollutants ; Epidemiologic Methods ; Female ; Humans ; Intestinal Neoplasms/etiology ; Male ; Mesothelioma/etiology ; Middle Aged ; Pleural Neoplasms/etiology ; United States ; }, } @article {pmid7029102, year = {1981}, author = {Harington, JS}, title = {Fiber carcinogenesis: epidemiologic observations and the Stanton hypothesis.}, journal = {Journal of the National Cancer Institute}, volume = {67}, number = {5}, pages = {977-989}, pmid = {7029102}, issn = {0027-8874}, mesh = {Analysis of Variance ; Animals ; Asbestos/adverse effects ; Environmental Exposure ; Humans ; Injections ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Minerals/*adverse effects ; *Models, Biological ; Neoplasms, Experimental/etiology ; Occupational Diseases/etiology ; Particle Size ; Pleural Neoplasms/etiology ; Rats ; South Africa ; Turkey ; }, } @article {pmid6918119, year = {1981}, author = {Brochard, P and Ameille, J}, title = {[Pathology relating to the inhalation of asbestos].}, journal = {Soins; la revue de reference infirmiere}, volume = {26}, number = {22}, pages = {31-36}, pmid = {6918119}, issn = {0038-0814}, mesh = {Asbestos/*adverse effects ; Asbestosis/*diagnosis/etiology ; Bronchial Neoplasms/etiology ; Humans ; Mesothelioma/*etiology ; Pleural Neoplasms/*etiology ; }, } @article {pmid6170430, year = {1981}, author = {Holiat, SM and Smith, WE and Hubert, DD and Davis, S}, title = {Chemotherapeutic trials with hamster mesothelioma 10-24: responses to azacitidine, aziridinylbenzoquinone, cisplatin, and PCNU.}, journal = {Cancer treatment reports}, volume = {65}, number = {11-12}, pages = {1113-1115}, pmid = {6170430}, issn = {0361-5960}, mesh = {Animals ; Antineoplastic Agents/*administration & dosage ; Azacitidine/*administration & dosage ; Aziridines/*administration & dosage ; Azirines/*administration & dosage ; *Benzoquinones ; Cisplatin/administration & dosage ; Cricetinae ; Cyclohexenes ; Drug Administration Schedule ; Drug Evaluation, Preclinical ; Male ; Mesocricetus ; Mesothelioma/*drug therapy ; Mustard Compounds/administration & dosage ; Neoplasm Transplantation ; Neoplasms, Experimental/drug therapy ; Nitrosourea Compounds/*administration & dosage ; Time Factors ; }, abstract = {Asbestos-induced peritoneal mesothelioma 10-24 serially transplanted in Syrian golden hamsters was used to test responses to seven drugs as single agents. Compared to saline-treated controls, the average survival time increased 51%-85% with azactitidine, 42%-60% with aziridinylbenzoquinone, 43% with cisplatin, and 35%-45% with PCNU. No cures were achieved. Therapeutic responses were not observed with dactinomycin, dianhydroxyanthracenedione, or DTIC.}, } @article {pmid6273705, year = {1981}, author = {Sommer, T and Kantartzis, M and Garcia, M and Schubert, GE}, title = {[Pleural metastases can simulate a mesothelioma].}, journal = {Medizinische Klinik}, volume = {76}, number = {22}, pages = {626-629}, pmid = {6273705}, issn = {0025-8458}, mesh = {Adenocarcinoma, Mucinous/diagnosis/pathology/*secondary ; Adult ; Diagnosis, Differential ; Humans ; Male ; Mesothelioma/*diagnosis ; Pleura/pathology ; Pleural Neoplasms/diagnosis/pathology/*secondary ; Stomach/pathology ; Stomach Neoplasms/*diagnosis/pathology ; }, abstract = {We are reporting about an inoperable cell carcinoma of the stomach, which exclusively caused thoracal pains due to metastases into a pleural thickening. First this symptomatology with thoracal pains and recurring pleural effusions was thought to be a pleural mesothelioma. Only the immediate histological examination of the tissue showed the origin of the tumor. Although cancer of stomach appears very commonly, this tumor is often diagnosed too late and in most cases it is already inoperable. Even nowadays more than 75% of the patients with a cancer of the stomach die of their metastases, although diagnosis and therapy have been developed. - Pleural mesotheliomas are rare; nevertheless the possibility of a mesothelioma in connection with all pleural effusions of a vague genesis should be considered. The exposure to asbestos strengthens the suspicion that this tumor is existing. In connection with a pleural mesothelioma an indurative pleurisy, a primary cancer of the lung and - like in our case - pleural metastases of a primary cancer of another site have to be differentiated.}, } @article {pmid7306467, year = {1981}, author = {Dorward, AJ and Stack, BH}, title = {Diffuse malignant pleural mesothelioma in Glasgow.}, journal = {British journal of diseases of the chest}, volume = {75}, number = {4}, pages = {397-402}, doi = {10.1016/0007-0971(81)90027-9}, pmid = {7306467}, issn = {0007-0971}, mesh = {Aged ; Asbestos/adverse effects ; Female ; Humans ; Male ; Mesothelioma/*epidemiology/etiology/pathology ; Middle Aged ; Occupational Diseases/epidemiology ; Pleural Neoplasms/*epidemiology/etiology/pathology ; Prognosis ; Retrospective Studies ; Scotland ; }, abstract = {Thirty-two patients seen in one area between 1974 and 1980 with a diagnosis of malignant pleural mesothelioma are reviewed retrospectively. Asbestos contact, often in the shipyards, was found in 80%. The average age at diagnosis was 64 years and chest pain or breathlessness were the most common initial symptoms. Radiology usually confirmed a pleural effusion, but rarely also showed pleural plaques or asbestosis. The most useful diagnostic investigation was pleural biopsy, with a 59% success rate. Post mortem examinations showed widespread infiltration of adjacent tissues in many, with haematogenous metastases in 52%. Prognosis was poor, with an average survival of 40 weeks from presentation. No treatment improved life expectancy. Thoracotomy was followed by painful chest wall masses. The incidence of mesothelioma in our area is six times higher than in the rest of Scotland. As the disease has a long latent period between asbestos exposure and appearance, it will be many years before this rate is significantly reduced.}, } @article {pmid7292052, year = {1981}, author = {Sasser, WF and Bari, WA}, title = {Surgical and pathologic aspects of asbestosis.}, journal = {Southern medical journal}, volume = {74}, number = {10}, pages = {1178-9, 1185}, doi = {10.1097/00007611-198110000-00005}, pmid = {7292052}, issn = {0038-4348}, mesh = {Adenocarcinoma/etiology/*pathology ; Aged ; Asbestosis/diagnostic imaging/*pathology ; Humans ; Lung Neoplasms/etiology/*pathology ; Male ; Mesothelioma/etiology/pathology ; Middle Aged ; Radiography ; Smoking ; }, abstract = {We studied 12 patients with occupational exposure to asbestos to evaluate the pulmonary diseases that result from protracted exposure to this fibrogenic and oncogenic fiber. The spectrum of diseases includes diffuse interstitial fibrosis, bronchogenic carcinoma, and malignant mesothelioma. Cigarette smoking is found to be a cocarcinogen with asbestos. Because of the impairment of pulmonary function in these patients, surgery plays a limited role in their management.}, } @article {pmid7280715, year = {1981}, author = {Antman, KH}, title = {Clinical presentation and natural history of benign and malignant mesothelioma.}, journal = {Seminars in oncology}, volume = {8}, number = {3}, pages = {313-320}, pmid = {7280715}, issn = {0093-7754}, support = {CA09172/CA/NCI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Asbestos/adverse effects ; Child ; Environmental Exposure ; Female ; Heart Neoplasms/diagnosis/pathology ; Humans ; Male ; Mesothelioma/*diagnosis/*pathology ; Middle Aged ; Pericardium/pathology ; Peritoneal Neoplasms/diagnosis/pathology ; Pleural Effusion/pathology ; Pleural Neoplasms/diagnosis/pathology ; Prognosis ; }, } @article {pmid7280713, year = {1981}, author = {Solomon, A}, title = {The radiology of asbestos-related diseases with special reference to diffuse mesothelioma.}, journal = {Seminars in oncology}, volume = {8}, number = {3}, pages = {290-301}, pmid = {7280713}, issn = {0093-7754}, mesh = {Adult ; Asbestos/adverse effects ; Asbestosis/*diagnostic imaging ; Calcinosis/diagnostic imaging ; Environmental Exposure ; Female ; Humans ; Lung Neoplasms/diagnostic imaging ; Male ; Mesothelioma/*diagnostic imaging ; Pleura/diagnostic imaging ; Pleural Diseases/diagnostic imaging ; Pleural Effusion/diagnostic imaging ; Pleural Neoplasms/*diagnostic imaging ; Radiography ; }, } @article {pmid7280712, year = {1981}, author = {Gupta, PK and Frost, JK}, title = {Cytologic changes associated with asbestos exposure.}, journal = {Seminars in oncology}, volume = {8}, number = {3}, pages = {283-289}, pmid = {7280712}, issn = {0093-7754}, support = {NIH-NO1-CB-92172/CB/NCI NIH HHS/United States ; NIH-NO1-CN-45037/CN/NCI NIH HHS/United States ; }, mesh = {Asbestos/*adverse effects ; Asbestosis/etiology/*pathology ; Bronchi/pathology ; Bronchial Neoplasms/*pathology ; Environmental Exposure ; Humans ; Iron/analysis ; Lung/pathology ; Lung Neoplasms/*pathology ; Male ; Mesothelioma/*pathology ; Metalloproteins/analysis ; Metaplasia ; Smoking ; Sputum ; }, } @article {pmid7280710, year = {1981}, author = {Kagan, E}, title = {The alveolar macrophage: immune derangement and asbestos-related malignancy.}, journal = {Seminars in oncology}, volume = {8}, number = {3}, pages = {258-267}, pmid = {7280710}, issn = {0093-7754}, mesh = {Animals ; Asbestos/*adverse effects ; Asbestosis/*immunology ; Carcinoma, Bronchogenic/etiology/immunology ; Humans ; Immunity, Cellular ; Leukemia/etiology/immunology ; Lung Neoplasms/etiology/*immunology ; Lymphocyte Activation ; Macrophages/*immunology ; Mesothelioma/etiology/immunology ; Phagocytosis ; Pulmonary Alveoli/*immunology ; Rats ; }, } @article {pmid7280709, year = {1981}, author = {Newhouse, M}, title = {Epidemiology of asbestos-related tumors.}, journal = {Seminars in oncology}, volume = {8}, number = {3}, pages = {250-257}, pmid = {7280709}, issn = {0093-7754}, mesh = {Asbestos/*adverse effects ; Female ; Follow-Up Studies ; Gastrointestinal Neoplasms/*epidemiology/etiology ; Humans ; Laryngeal Neoplasms/*epidemiology/etiology ; Lung Neoplasms/*epidemiology/etiology ; Male ; Mesothelioma/*epidemiology/etiology ; Occupational Diseases/*epidemiology ; Sex Factors ; Smoking ; Time Factors ; }, abstract = {Epidemiologic evidence has helped in defining and measuring the risks of asbestos exposure. Further investigations are required to confirm the differing carcinogenicity of the various types of asbestos and related fibers. The evidence relating crocidolite asbestos to malignancy is not universally accepted. Most standards for concentrations of asbestos in the air are currently being adopted and the proposed British standard is about to be reduced to 1 fiber per milliliter for chrysotile asbestos, 0.5 fiber per milliliter for amosite and is to remain at 0.2 fiber per milliliter for crocidolite asbestos. 37 Careful prospective studies are still required in order to evaluate the efficacy of these standards in the prevention of asbestos related diseases. In addition, further epidemiologic studies are necessary to determine the relationship between asbestos exposure, particularly the low level exposure, and its potential cocarcinogenic role with other carcinogens in the evolution of the wide spectrum of human malignancy.}, } @article {pmid7280708, year = {1981}, author = {Pooley, FD}, title = {Mineralogy of asbestos: the physical and chemical properties of the dusts they form.}, journal = {Seminars in oncology}, volume = {8}, number = {3}, pages = {243-249}, pmid = {7280708}, issn = {0093-7754}, mesh = {Animals ; *Asbestos/adverse effects ; Chemical Phenomena ; Chemistry ; Crystallography ; Dust ; Humans ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Particle Size ; Rats ; }, } @article {pmid7280707, year = {1981}, author = {}, title = {Asbestos-related neoplasms.}, journal = {Seminars in oncology}, volume = {8}, number = {3}, pages = {241-346}, pmid = {7280707}, issn = {0093-7754}, mesh = {Animals ; Asbestos/*adverse effects ; Asbestosis/*complications ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; }, } @article {pmid7280706, year = {1981}, author = {Aisner, J and Wiernik, PH}, title = {Asbestos-related neoplasms. Introduction.}, journal = {Seminars in oncology}, volume = {8}, number = {3}, pages = {241-242}, pmid = {7280706}, issn = {0093-7754}, mesh = {Asbestos/*adverse effects ; Asbestosis/*complications ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; }, } @article {pmid7314258, year = {1981}, author = {Bianchi, C and Brollo, A and Miniussi, C and Bittesini, L}, title = {Asbestos exposure in the Monfalcone area. A social and pathological study of 100 autopsy cases.}, journal = {Tumori}, volume = {67}, number = {4}, pages = {279-282}, doi = {10.1177/030089168106700403}, pmid = {7314258}, issn = {0300-8916}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Asbestosis/*etiology ; Autopsy ; Female ; Humans ; Italy ; Male ; Mesothelioma/*etiology ; Middle Aged ; Occupations ; Pleural Neoplasms/*etiology ; Risk ; Ships ; }, abstract = {Monfalcone is a coastal town with important shipyards. In the present investigation hyalin pleural plaques, lung asbestos bodies, and occupational history were studied in 100 consecutive autopsy cases, collected at the hospital of Monfalcone. Pleural plaques were observed in 72% of males and in 33% of females. Asbestos bodies were found after chemical digestion of pulmonary tissue in 94 cases, and an approximate estimation of their amount showed high or very high numbers in 39 cases. Occupational history, obtained from patients' relatives, was suggestive of occupational asbestos exposure in 60 cases, with 37 subjects having worked in the shipyards. Thirteen other patients had had a probable domestic exposure to asbestos. The severity of asbestos exposure in the Monfalcone area is emphasized.}, } @article {pmid6789635, year = {1981}, author = {Alexander, E and Clark, RA and Colley, DP and Mitchell, SE}, title = {CT of malignant pleural mesothelioma.}, journal = {AJR. American journal of roentgenology}, volume = {137}, number = {2}, pages = {287-291}, doi = {10.2214/ajr.137.2.287}, pmid = {6789635}, issn = {0361-803X}, mesh = {Aged ; Asbestos ; Environmental Exposure ; Female ; Humans ; Male ; Mediastinal Neoplasms/diagnostic imaging ; Mesothelioma/*diagnostic imaging ; Middle Aged ; Pleural Effusion/diagnostic imaging ; Pleural Neoplasms/*diagnostic imaging ; *Tomography, X-Ray Computed ; }, abstract = {Malignant pleural mesothelioma is a rare tumor. Although the chest film findings of pleural mesothelioma are well described, there are few descriptions of the findings of computed tomography (CT). This report describes the CT findings in five cases of pleural mesothelioma. In each case the CT showed an extensive, irregular, pleural-based mass surrounding the lung, spreading into the fissures, and extending into the mediastinum. In two cases there was also extension into the contralateral chest, and in one case each there was extension into the abdomen and chest wall. In each case the chest radiographs underestimated the extent of disease, when compared to CT. When an irregular, pleural-based mass involving most of the hemithorax is identified on CT, the diagnosis of mesothelioma can be suggested and at the same time the extent of the tumor may be evaluated. This is important because the diagnosis of mesothelioma is difficult and because treatment and prognosis may depend on the extent of the disease.}, } @article {pmid7312436, year = {1981}, author = {Bianchi, C and Brollo, A and Bittesini, L}, title = {[Mesothelioma caused by asbestos in the Monfalcone area].}, journal = {Pathologica}, volume = {73}, number = {1026}, pages = {649-655}, pmid = {7312436}, issn = {0031-2983}, mesh = {Aged ; Asbestosis/*complications ; Female ; Humans ; Italy ; Leukemia, Lymphoid/*etiology ; Male ; Mesothelioma/complications/*etiology ; Middle Aged ; Occupational Diseases/*epidemiology ; Pleural Neoplasms/*etiology ; }, } @article {pmid6786728, year = {1981}, author = {Iozzo, RV and Goldes, JA and Chen, WJ and Wight, TN}, title = {Glycosaminoglycans of pleural mesothelioma: a possible biochemical variant containing chondroitin sulfate.}, journal = {Cancer}, volume = {48}, number = {1}, pages = {89-97}, doi = {10.1002/1097-0142(19810701)48:1<89::aid-cncr2820480118>3.0.co;2-b}, pmid = {6786728}, issn = {0008-543X}, support = {ES-00677/ES/NIEHS NIH HHS/United States ; HL-07312/HL/NHLBI NIH HHS/United States ; }, mesh = {Aged ; Asbestos/analysis ; Chondroitin Sulfates/metabolism ; Glycosaminoglycans/*metabolism ; Humans ; Hyaluronic Acid/metabolism ; Lung/metabolism ; Lung Neoplasms/metabolism ; Male ; Mesothelioma/*metabolism/pathology ; Pleural Neoplasms/*metabolism/pathology ; }, abstract = {Glycosaminoglycans of a malignant pleural mesothelioma have been characterized histochemically and biochemically and compared with those of normal lung, pleural plaque, lung carcinoma, and other connective tissue neoplasms. Chondroitin sulfate constituted the major glycosaminoglycan (approximately 80% of total) present in the pleural mesothelioma while hyaluronic acid was present in only trace amounts (approximately 3% of total). In particular chondroitin 6-sulfate was the predominant isomer, constituting 80% of the total chondroitin sulfate. Control tissue exhibited different proportions of glycosaminoglycans and none of them contained as high an absolute concentration of chondroitin sulfate as the mesothelioma. These findings differ from previous reports demonstrating increased concentration of hyaluronic acid in mesothelioma and suggest the possible existence of a biochemically different form of this neoplasm.}, } @article {pmid6454455, year = {1981}, author = {Britton, MG and Hughes, DT and Phillips, TJ}, title = {A guide to compensation for asbestos-related diseases.}, journal = {British medical journal (Clinical research ed.)}, volume = {282}, number = {6282}, pages = {2107-2111}, pmid = {6454455}, issn = {0267-0623}, mesh = {Asbestos/*adverse effects ; Asbestosis/economics ; Death ; Humans ; Lung Neoplasms/economics/etiology ; Male ; Mesothelioma/economics/etiology ; Occupational Diseases/*economics ; United Kingdom ; *Workers' Compensation ; }, } @article {pmid7233304, year = {1981}, author = {Cochrane, JC and Webster, I}, title = {Mesothelioma in relaxation to asbestos fibre exposure.}, journal = {South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde}, volume = {59}, number = {24}, pages = {848}, pmid = {7233304}, issn = {0256-9574}, mesh = {Asbestos/*adverse effects ; Humans ; Lung Neoplasms/etiology ; Male ; Medical History Taking ; Mesothelioma/*etiology ; Middle Aged ; }, } @article {pmid7313614, year = {1981}, author = {Gylseth, B and Mowé, G and Skaug, V and Wannag, A}, title = {Inorganic fibers in lung tissue from patients with pleural plaques or malignant mesothelioma.}, journal = {Scandinavian journal of work, environment & health}, volume = {7}, number = {2}, pages = {109-113}, doi = {10.5271/sjweh.2559}, pmid = {7313614}, issn = {0355-3140}, mesh = {Adult ; Aged ; Aging ; Asbestos/*analysis ; Female ; Humans ; Lung/*pathology ; Lung Neoplasms/*pathology ; Male ; Mesothelioma/*pathology ; Middle Aged ; Occupational Diseases/pathology ; Pleural Diseases/*pathology ; Sex Factors ; }, abstract = {The concentration of inorganic fibers in the lungs of patients with malignant mesothelioma and pleural plaques has been compared to that of patients without cancer or chronic respiratory diseases. The fiber concentrations have been determined by scanning electron microscopy and given as number of fibers per gram of dried tissue. A statistically significant difference in inorganic fiber content was found between the different groups.}, } @article {pmid7260861, year = {1981}, author = {Briselli, M and Mark, EJ and Dickersin, GR}, title = {Solitary fibrous tumors of the pleura: eight new cases and review of 360 cases in the literature.}, journal = {Cancer}, volume = {47}, number = {11}, pages = {2678-2689}, doi = {10.1002/1097-0142(19810601)47:11<2678::aid-cncr2820471126>3.0.co;2-9}, pmid = {7260861}, issn = {0008-543X}, mesh = {Adult ; Aged ; Cell Nucleus/ultrastructure ; Cough/diagnosis ; Dyspnea/diagnosis ; Female ; Fibroblasts/ultrastructure ; Humans ; Male ; Mesothelioma/*diagnosis/ultrastructure ; Microscopy, Electron ; Middle Aged ; Mitosis ; Osteoarthropathy, Secondary Hypertrophic/diagnosis ; Pleural Neoplasms/*diagnosis/ultrastructure ; Prognosis ; }, abstract = {Three-hundred-sixty cases of solitary fibrous tumor of the pleura from the literature are analyzed, and eight new cases are described. Of patients reported on prior to 1972, 72% had symptoms due to the tumor at the time of diagnosis, but only 54% of patients reported on since then were symptomatic. This probably reflects earlier diagnosis as a result of increased use of chest radiographs in asymptomatic populations. Cough, chest pain, dyspnea, and/or pulmonary osteoarthropathy are each found in at least one-third of patients who have symptoms. Approximately 80% of solitary fibrous tumors of the pleura originate in the visceral and 20% in the parietal pleura. In the literature and in this experience these tumors are on the whole circumscribed. The range in size from 1-36 cm with a mean of 6 cm. Many are pedunculated on pleural-based pedicles that contain hypertrophic arteries and veins. Histologic examination of the tumor usually discloses cellular areas alternating with hyalinized and/or necrotic areas. Spindle-shaped cells typically have minimal nuclear pleomorphism and rare or absent mitoses. Numerous thin-walled vessels constitute an additional feature of large tumors. Electron microscopical examination reveals features of both fibroblasts and mesothelial cells. Solitary fibrous tumors behave in a benign fashion in 88% of cases after surgical resection. In 12% of the cases the tumor is responsible for the patient's death because of its extensive intrathoracic growth, by virtue of either late diagnosis or unresectable recurrence. No single histologic feature allows a definite prognosis. The best indicator of a good prognosis is the presence of a pedicle supporting the tumor. Also favorable in circumscription of the tumor without invasion of lung, mediastinum, or chest wall. Nuclear pleomorphism and a high mitotic rate are seen in larger tumors but do not necessarily indicate a poor prognosis if the tumor is circumscribed. Solitary fibrous tumors of the pleura are not associated with asbestos.}, } @article {pmid7232722, year = {1981}, author = {Mintzer, RA and Gore, RM and Vogelzang, RL and Holz, S}, title = {Rounded atelectasis and its association with asbestos-induced pleural disease.}, journal = {Radiology}, volume = {139}, number = {3}, pages = {567-570}, doi = {10.1148/radiology.139.3.7232722}, pmid = {7232722}, issn = {0033-8419}, mesh = {Aged ; Asbestos/*adverse effects ; Diagnosis, Differential ; Humans ; Male ; Middle Aged ; Pleural Diseases/complications/diagnostic imaging/*etiology ; Pulmonary Atelectasis/*diagnostic imaging/etiology ; Radiography ; }, abstract = {Rounded atelectasis (RA) is an unusual form of peripheral lobar collapse which may present as a juxtapleural mass simulating a pulmonary neoplasm. Seven cases of RA were recently encountered in patients with asbestos-induced pleural disease. Since asbestos exposure is associated with mesothelioma, bronchogenic carcinoma, and other tumors, differentiation of RA from these neoplasms is essential in avoiding unnecessary thoracotomy. The radiographic features of RA are sufficiently characteristic, so that in the presence of chronic pleural thickening due to asbestos exposure, the diagnosis can be made with assurance and further work-up avoided.}, } @article {pmid6894526, year = {1981}, author = {Warren, S and Brown, CE and Chute, RN and Federman, M}, title = {Mesothelioma relative to asbestos, radiation, and methylcholanthrene.}, journal = {Archives of pathology & laboratory medicine}, volume = {105}, number = {6}, pages = {305-312}, pmid = {6894526}, issn = {0003-9985}, mesh = {Animals ; *Asbestos ; Asbestosis/complications ; Female ; Lung Neoplasms/etiology ; Lymphocytes/pathology ; Macrophages/pathology ; Male ; Mesothelioma/complications/*etiology ; Methylcholanthrene ; Neoplasms, Radiation-Induced/*etiology ; Neutrophils/pathology ; Rats ; X-Rays ; }, abstract = {The carcinogenicity of chrysotile asbestos fibers (Canadian and Rhodesian) for the mesothelium of pleura and peritoneum of NEDH rats was explored by injection of 2 mg of asbestos fibers suspended in saline intratracheally, intrapleurally, or intraperitoneally, with or without ancillary radiation treatment (1,000 rad to the whole body of parabiont rats or 2,000 rad to the right thorax of single rats), or alternatively, by injection of asbestos plus 1 mg of 3-methylcholanthrene. A highly significant incidence of mesothelioma (3.8%) was noted in 159 rats treated with asbestos alone, as compared with 0.1% in 1,417 control rats. Additional treatment with radiation or 3-methylcholanthrene increased this incidence to 11.8% and 25.5%, respectively, the latter increase alone being significant at the .01 level of probability.}, } @article {pmid7254106, year = {1981}, author = {Young, I and West, S and Jackson, J and Cantrell, P}, title = {Prevalence of asbestos related lung disease among employees in non-asbestos industries.}, journal = {The Medical journal of Australia}, volume = {1}, number = {9}, pages = {464-467}, doi = {10.5694/j.1326-5377.1981.tb135736.x}, pmid = {7254106}, issn = {0025-729X}, mesh = {Adult ; Age Factors ; Aged ; Asbestos/*adverse effects ; Asbestosis/epidemiology ; Australia ; Humans ; Lung Diseases/*etiology ; Male ; Middle Aged ; Occupational Diseases/*epidemiology/etiology ; Pleural Diseases/epidemiology/etiology ; Respiratory Function Tests ; }, abstract = {Employees from two non-asbestos industries wee examined to assess the prevalence of asbestos-related lung disease. Of the 214 employees, one suffered from a malignant mesothelioma of the pleura and in 13 (6.1%), pleural plaques were diagnosed radiologically. the plaques were symptomless and not associated with any disturbance in respiratory function. The sole source of asbestos fibre in one factory was the asbestos insulation surrounding steam and hot water pipes similar to that found throughout industry. Exposure occurred as the result of the way in which this insulation has been handled routinely in industry by people who have commonly been unaware either of their exposure or of its significance. In the second factory there was the possibility of additional exposure originating from a neighbouring industry that was a major consumer of asbestos. The results suggest that maintenance workers may be particularly at risk and that the presence of pleural plaques may be under-reported in the absence of a history of asbestos exposure to direct attention towards them. The presence of pleural plaques has important consequences for the individual and for others who have shared the work environment.}, } @article {pmid6112395, year = {1981}, author = {Baris, YI and Saracci, R and Simonato, L and Skidmore, JW and Artvinli, M}, title = {Malignant mesothelioma and radiological chest abnormalities in two villages in Central Turkey. An epidemiological and environmental investigation.}, journal = {Lancet (London, England)}, volume = {1}, number = {8227}, pages = {984-987}, doi = {10.1016/s0140-6736(81)91742-6}, pmid = {6112395}, issn = {0140-6736}, mesh = {Adolescent ; Adult ; Aged ; Aluminum Silicates/*adverse effects ; Asbestos ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Pleura/*diagnostic imaging ; Pleural Neoplasms/*epidemiology/etiology ; Radiography ; Rural Health ; Turkey ; }, abstract = {A comparative epidemiological and environmental study in two neighbouring villages, Karain and Karlin, in Central Turkey showed an excess adult mortality, shortening of life expectancy, and an excess of pleural radiological abnormalities in Karain. This supports an earlier report of an endemic of pleural mesothelioma in the village. Concentrations of airborne respirable fibres were uniformly very low in Karlik and higher in some of the air samples from Karain, the fibres being similar in composition to those of erionite-a mineral of the zeolite family and the major contributor to the Karain clouds. This is compatible with the hypothesis of a causal association between endemic mesothelioma and inhalation of erionite fibres, but the fibre concentrations in all samples are so low as to leave in question the aetiological role of erionite. In addition to their local importance these results may have relevance for the wider scientific and public-health issue of long-term inhalation of mineral fibres at low concentrations.}, } @article {pmid7257347, year = {1981}, author = {Taylor, RA and Johnson, LP}, title = {Mesothelioma: current perspectives.}, journal = {The Western journal of medicine}, volume = {134}, number = {5}, pages = {379-383}, pmid = {7257347}, issn = {0093-0415}, mesh = {Asbestos/adverse effects ; Female ; Humans ; Male ; Mesothelioma/*diagnosis/epidemiology/etiology ; Middle Aged ; Peritoneal Neoplasms/*diagnosis/epidemiology/etiology ; Pleural Neoplasms/*diagnosis/epidemiology/etiology ; Washington ; }, abstract = {Thirty patients with the diagnosis of mesothelioma were admitted to the Swedish Hospital Medical Center, Seattle, from 1975 to 1979. Of these, 26 had pleural and 4 had peritoneal mesothelioma. In 20 of the patients with pleural mesothelioma, the diagnosis had been made by open thoractomy and in only one by needle biopsy of the pleura. The average survival of the patients with pleural tumors from time of diagnosis was 15 months, and two are alive at three and eight months, respectively, one of whom had an apparent solitary benign mesothelioma. The average survival of those with peritoneal mesothelioma was ten months, although one has survived six years. There were 17 patients with a known history of exposure to asbestos, 14 while working in shipyards. Because of the relatively high incidence of this previously rare tumor in the Puget Sound, Washington, area, and the generally dismal results of therapy, better methods of diagnosis including thoracoscopy and a more systematic approach to treatment are recommended.}, } @article {pmid7236537, year = {1981}, author = {Berry, G}, title = {Mortality of workers certified by pneumoconiosis medical panels as having asbestosis.}, journal = {British journal of industrial medicine}, volume = {38}, number = {2}, pages = {130-137}, pmid = {7236537}, issn = {0007-1072}, mesh = {Adult ; Age Factors ; Aged ; Asbestosis/*mortality ; Disability Evaluation ; Female ; Follow-Up Studies ; Humans ; Life Expectancy ; London ; Lung Neoplasms/mortality ; Male ; Mesothelioma/mortality ; Middle Aged ; Occupational Diseases/mortality ; Wales ; }, abstract = {A mortality study has been carried out at the London, Cardiff, or Swansea Pneumoconiosis Medical Panels between 1952 and 1976 on people certified as suffering from asbestosis. The main analysis was of 665 men, 283 of whom had died. Of the deaths, 39% were from lung cancer, 9% mesothelioma, and 20% asbestosis. The observed mortality was compared with expectation based on the death rates for England and Wales. For all causes the observed number of deaths was 2.6 times expectation and for lung cancer 9.1 times expectation. After 10 years from first certification half of the men had died compared with an expectation of one in four. The excess death rates were apparent in the first year after certification and were still operating after 10 years on those who survived until then. The main factor influencing the mortality was the clinical state of the men at the time of certification, as indicated by the percentage disability awarded; the excess lung cancer rate and the mesothelioma and asbestosis rates all increased with percentage disability. Those awarded only 10% or 20% benefit were still at risk from all the three asbestos-related causes. For a man certified at age 55 it was estimated that his life expectation would be reduced by 3, 5, 8, or 12 years according to whether his rate of disablement benefit was 10%, 20%, 30% or 40% , or 50% or more respectively.}, } @article {pmid7030603, year = {1981}, author = {Casey, KR and Rom, WN and Moatamed, F}, title = {Asbestos-related diseases.}, journal = {Clinics in chest medicine}, volume = {2}, number = {2}, pages = {179-202}, pmid = {7030603}, issn = {0272-5231}, mesh = {Asbestos/*adverse effects ; Asbestosis/diagnosis/etiology/immunology ; Carcinoma, Bronchogenic/etiology ; Humans ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Occupational Diseases/*etiology ; Peritoneal Neoplasms/etiology ; Pleural Diseases/etiology ; Pleural Neoplasms/etiology ; }, } @article {pmid6262566, year = {1981}, author = {Sebastien, P and Gaudichet, A and Bignon, J and Baris, YI}, title = {Zeolite bodies in human lungs from Turkey.}, journal = {Laboratory investigation; a journal of technical methods and pathology}, volume = {44}, number = {5}, pages = {420-425}, pmid = {6262566}, issn = {0023-6837}, mesh = {Aluminum Silicates/*analysis ; Asbestosis/*pathology ; Humans ; Lung Neoplasms/*pathology ; Mesothelioma/*pathology ; Microscopy, Electron/methods ; Turkey/ethnology ; Zeolites ; }, abstract = {It is thought that the extremely high occurrence of malignant pleural mesothelioma in the two Turkish villages of Karain and Tusköy could be related to environmental zeolite fibers. Mineral fibers were assessed in lung samples from two cases of malignant pleural mesothelioma in Tusköy, using the light microscope and the analytical transmission electron microscope. Zeolite (erionite) fibers and ferruginous bodies, formed around zeolite fibers (zeolite bodies), were frequently encountered in these samples. Under the light microscope, zeolite bodies were morphologically identical to typical asbestos bodies. To document the zeolite exposure in this area of Turkey, it is suggested that a biologic monitoring study be performed in villages in which mesotheliomas occur and in control villages, by testing for the presence of zeolite bodies in sputum.}, } @article {pmid7207561, year = {1981}, author = {Roggli, VL}, title = {Pericardial mesothelioma after exposure to asbestos.}, journal = {The New England journal of medicine}, volume = {304}, number = {17}, pages = {1045}, doi = {10.1056/nejm198104233041718}, pmid = {7207561}, issn = {0028-4793}, mesh = {Asbestos/*adverse effects ; Environmental Exposure ; Heart Neoplasms/*etiology ; Humans ; Male ; Mesothelioma/*etiology ; Middle Aged ; *Pericardium ; }, } @article {pmid7226093, year = {1981}, author = {Humphrey, EW and Ewing, SL and Wrigley, JV and Northrup, WF and Kersten, TE and Mayer, JE and Varco, RL}, title = {The production of malignant tumors of the lung and pleura in dogs from intratracheal asbestos instillation and cigarette smoking.}, journal = {Cancer}, volume = {47}, number = {8}, pages = {1994-1999}, doi = {10.1002/1097-0142(19810415)47:8<1994::aid-cncr2820470816>3.0.co;2-c}, pmid = {7226093}, issn = {0008-543X}, mesh = {Adenocarcinoma/etiology/pathology ; Animals ; *Asbestos ; Dogs ; Lung Neoplasms/*etiology ; Male ; Mesothelioma/etiology/pathology ; Neoplasms, Experimental/etiology/pathology ; Pleural Neoplasms/*etiology/pathology ; Pulmonary Fibrosis/etiology/pathology ; *Smoking ; Time Factors ; }, abstract = {Nine dogs were given early intratracheal instillations of crocidolite asbestos for periods up to three years. The maximum dose totalled 66 mg/kg. In addition, seven of these dogs smoked nine cigarettes per day, five days per week for six years. A malignant pleural and/or peritoneal mesothelioma developed in six of these dogs, and adenocarcinoma of the lung developed in four, one of which had areas of squamous differentiation. The first animal died of a malignant tumor six years after the onset of exposure, and the last animal died eight years after the onset.}, } @article {pmid7258177, year = {1981}, author = {Brenner, J and Sordillo, PP and Magill, GB and Golbey, RB}, title = {Malignant peritoneal mesothelioma: review of 25 patients.}, journal = {The American journal of gastroenterology}, volume = {75}, number = {4}, pages = {311-313}, pmid = {7258177}, issn = {0002-9270}, mesh = {Adolescent ; Adult ; Aged ; Female ; Hormones, Ectopic/biosynthesis ; Humans ; Male ; *Mesothelioma ; Middle Aged ; *Peritoneal Neoplasms ; Prognosis ; }, abstract = {Twenty-five patients with malignant peritoneal mesothelioma have been seen in Memorial Hospital since 1950. None of them had a history of exposure to asbestos and no clear etiologic factor could be determined in any of the patients. Two patients had signs of ectopic hormone production. The tumors tended to be locally invasive but distant hematogenous metastases were not seen in any of the patients. Surgery was not effective, as most patients had extensive intra-abdominal disease at the time of laparotomy. There were four long-term survivors. All of them were treated with external radiotherapy and 32P instillation after surgery. The response to chemotherapy was poor except for one partial response to combined therapy with adriamycin and radiation. Most patients died of extensive abdominal disease with a median survival of only 12 months.}, } @article {pmid7235119, year = {1981}, author = {Foyle, A and Al-Jabi, M and McCaughey, WT}, title = {Papillary peritoneal tumors in women.}, journal = {The American journal of surgical pathology}, volume = {5}, number = {3}, pages = {241-249}, doi = {10.1097/00000478-198104000-00004}, pmid = {7235119}, issn = {0147-5185}, mesh = {Adult ; Aged ; Diagnosis, Differential ; Female ; Humans ; Hyperplasia ; Mesoderm/pathology ; Mesothelioma/diagnosis/pathology ; Middle Aged ; Peritoneal Neoplasms/*pathology/secondary ; }, abstract = {Twenty-five peritoneal tumors in women are described. All were partly or entirely of papillary or tubulopapillary structure and multifocal. Eight were unusually well-differentiated mesotheliomas. This appearance was associated with indolent behavior. In 10 cases the growth closely resembled serous papillary carcinoma, including the frequent presence of psammoma bodies, but the ovaries were free of primary tumor. The latter group of tumors progress rapidly and are thought to be derived from extraovarian mesothelium with müllerian potential. Four further cases showed some resemblance to ovarian papillary carcinoma. Only three tumors in the entire series (12%) closely resembled papillary or tubulopapillary diffuse malignant mesothelioma of the type that occurs in the pleural cavities in both sexes. The histopathologic spectrum of papillary tumors of peritoneum in women is extensive, and mesothelial tumors of the type known to be associated with asbestos are rare.}, } @article {pmid6938842, year = {1981}, author = {Vianna, NJ and Maslowsky, J and Roberts, S and Spellman, G and Patton, RB}, title = {Malignant mesothelioma; epidemiologic patterns in New York State.}, journal = {New York state journal of medicine}, volume = {81}, number = {5}, pages = {735-738}, pmid = {6938842}, issn = {0028-7628}, mesh = {Asbestos/adverse effects ; Female ; Humans ; Male ; Mesothelioma/*epidemiology/etiology ; New York ; Occupations ; Peritoneal Neoplasms/*epidemiology/etiology ; Pleural Neoplasms/*epidemiology/etiology ; Sex Ratio ; Talc/adverse effects ; }, } @article {pmid7314084, year = {1981}, author = {Sera, Y and Kang, KY}, title = {Asbestos and cancer in the Sennan District of Osaka.}, journal = {The Tohoku journal of experimental medicine}, volume = {133}, number = {3}, pages = {313-320}, doi = {10.1620/tjem.133.313}, pmid = {7314084}, issn = {0040-8727}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Asbestosis/epidemiology ; Female ; Humans ; Japan ; Lung Neoplasms/etiology ; Male ; Middle Aged ; Neoplasms/epidemiology/*etiology ; Occupational Diseases/*epidemiology ; Silicosis/epidemiology ; Stomach Neoplasms/etiology ; Textiles ; }, abstract = {The cancer incidence among asbestos workers in the Sennan District and its surrounding of Osaka Prefecture, Japan, and the results of a mass survey in the above area since 1957 were evaluated from view points of epidemiology. During the period from 1953 to 1979, 107 patients with asbestosis were admitted to this Hospital. Twenty-six (24%) of them died of various carcinoma; 21 had lung cancer, 2 pleural mesothelioma and 3 had stomach cancer. Respiratory insufficiency due to pulmonary asbestosis was responsible for 41 deaths (38%). by a cohort survey of the 297 asbestos workers in the same district, 4 cases of lung cancer, and 3 cases of gastric cancer were detected and cases of cohort survey were followed up for 19 years. Fifty-seven (10%) of 556 cases of silicosis and 14 (11%) of 125 cases of pneumoconiosis other than silicosis or asbestosis were found to have lung cancer, but no mesothelioma. These results indicate that lung cancer and mesothelioma are associated more frequently with asbestosis than with non-asbestos pneumoconiosis (p less than 0.001 as tested by chi2-test). The standardized mortality ratio of lung and stomach cancer among the inhabitants of the Sennan District was calculated based on the statistics during the period of 10 years (1968-1977). the ratio of observed death to expected death of both cancers was smaller than 1.1, and there was no significant increase of death of lung and stomach cancer, although the risk of lung cancer tended to increase among male inhabitants. Discussions were made on the problems related to asbestos industry.}, } @article {pmid6101235, year = {1981}, author = {Churg, AM and Warnock, ML}, title = {Asbestos and other ferruginous bodies: their formation and clinical significance.}, journal = {The American journal of pathology}, volume = {102}, number = {3}, pages = {447-456}, pmid = {6101235}, issn = {0002-9440}, support = {ES02117-02S1/ES/NIEHS NIH HHS/United States ; }, mesh = {Asbestos/*analysis ; *Dust ; Epidemiologic Methods ; Female ; Gastrointestinal Neoplasms/etiology ; Humans ; Iron/analysis ; Lung Neoplasms/etiology ; Male ; Mesothelioma/etiology ; Metalloproteins/*analysis ; Minerals ; Occupational Diseases/etiology ; Particle Size ; Talc/adverse effects/analysis ; }, abstract = {Analyses of asbestos bodies from the general population have confirmed that these structures, like asbestos bodies from the lungs of asbestos workers, contain an asbestos core. In members of the general population this core is almost always an amphibole, whereas asbestos workers may have bodies formed on either amphibole or chrysotile. Most adults have a few bodies, and increasing numbers are seen in blue collar workers and others who handle small amounts of the fiber, with the highest levels being seen in asbestos workers. In men with minimal or extensive occupational exposure, asbestos bodies are formed on the commercial fibers, amosite and crocidolite, whereas women also form a significant number of bodies on the noncommercial fibers, anthophyllite and tremolite. These findings suggest that women may be exposed to specific asbestos-containing products, eg, cosmetic talc. The commercial fibers found in women and white collar men probably reflect atmospheric pollution with asbestos. At the highest levels of exposure, numbers of asbestos bodies correlate in a general way with the presence of asbestosis, although no precise value has been determined above which asbestosis is always found. In persons with much lower or environmental exposure, there does not appear to be any correlation between numbers of bodies and disease, in particular between numbers of bodies and carcinoma of the lung or gastrointestinal tract. The situation for mesothelioma is uncertain.}, } @article {pmid6781599, year = {1981}, author = {Gloag, D}, title = {Asbestos fibres and the environment.}, journal = {British medical journal (Clinical research ed.)}, volume = {282}, number = {6264}, pages = {623-626}, pmid = {6781599}, issn = {0267-0623}, mesh = {Air Pollution ; Asbestos/*adverse effects ; Environmental Exposure ; Food Contamination ; Humans ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Public Health ; Public Policy ; Water Pollution ; }, } @article {pmid7226014, year = {1981}, author = {Smith, WE and Hubert, DD and Holiat, SM and Sobel, HJ and Davis, S}, title = {An experimental model for treatment of mesothelioma.}, journal = {Cancer}, volume = {47}, number = {4}, pages = {658-663}, doi = {10.1002/1097-0142(19810215)47:4<658::aid-cncr2820470407>3.0.co;2-s}, pmid = {7226014}, issn = {0008-543X}, mesh = {Animals ; Asbestos/adverse effects ; Body Weight ; Cricetinae ; Cyclophosphamide/*therapeutic use ; Disease Models, Animal ; Doxorubicin/*therapeutic use ; Fluorouracil/*therapeutic use ; Male ; Mesothelioma/*drug therapy/etiology ; Neoplasm Transplantation ; Neoplasms, Experimental/drug therapy/etiology ; Peritoneal Neoplasms/*drug therapy/etiology ; }, abstract = {A peritoneal mesothelioma was induced by asbestos in a hamster, and was established in serial transfer to new hosts by injection of peritoneal effusion containing tumor cells. Biologically and histopathologically, this tumor is similar to its human counterpart. Three drugs were tested for efficacy using this model. Survival time was used as the only parameter of response and was compared with survival time of controls. Survival time increased 25 to 50% after short regimens of doxorubicin or 5-fluorouracil. Survival time increased up to 308% after long-continued treatments with cyclophosphamide. No cures were achieved.}, } @article {pmid6780123, year = {1981}, author = {Gloag, D}, title = {Asbestos--can it be used safely?.}, journal = {British medical journal (Clinical research ed.)}, volume = {282}, number = {6263}, pages = {551-553}, pmid = {6780123}, issn = {0267-0623}, mesh = {Asbestos/*adverse effects ; Environmental Exposure ; Humans ; Industry ; Lung Neoplasms/*etiology ; Maximum Allowable Concentration ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; Risk ; }, } @article {pmid7234680, year = {1981}, author = {Friedrichs, KH and Otto, H}, title = {Fibers in human lung dust samples: a scanning electron microscope study.}, journal = {American Industrial Hygiene Association journal}, volume = {42}, number = {2}, pages = {150-156}, doi = {10.1080/15298668191419497}, pmid = {7234680}, issn = {0002-8894}, mesh = {Asbestos/*analysis ; Dust/*analysis ; Humans ; Lung/*analysis ; Lung Neoplasms/ultrastructure ; Mesothelioma/ultrastructure ; Microscopy, Electron, Scanning ; Occupational Diseases/pathology ; Particle Size ; }, abstract = {Since 1977, mesothelioma has been admitted as an occupational disease in the Federal Republic of Germany, if a previous exposure to asbestos at the working place can be proven. In practical work of pathologists the question arises as to how to proceed in the assessment of necropsy cases of mesothelioma, if the patient's occupational history is unknown. In this study, 100 necropsy cases of different exposure were examined by scanning electron microscopy. Concentration and length of fibers were used as criteria to distinguish between spontaneous and occupationally caused cases of mesothelioma. Calculation of the counting results showed that a distinction between the two groups is reliable when fibers greater than 5 micron in length are counted.}, } @article {pmid7221309, year = {1981}, author = {Vande Weyer, R}, title = {[Asbestos lung pathology in Belgium (author's transl)].}, journal = {Revue medicale de Bruxelles}, volume = {2}, number = {2}, pages = {69-81}, pmid = {7221309}, issn = {0035-3639}, mesh = {Asbestos/*adverse effects ; Asbestosis/*epidemiology/etiology ; Belgium ; Bronchial Neoplasms/etiology ; Humans ; Mesothelioma/etiology ; Pleural Diseases/etiology ; Pleural Neoplasms/etiology ; }, } @article {pmid7349783, year = {1981}, author = {Taba, AH}, title = {Problems of occupational carcinogenesis in developing countries.}, journal = {Cancer detection and prevention}, volume = {4}, number = {1-4}, pages = {25-30}, pmid = {7349783}, issn = {0361-090X}, mesh = {Carcinogens, Environmental ; Developing Countries ; Health Education ; Humans ; Maximum Allowable Concentration ; Neoplasms/*etiology/prevention & control ; Occupational Diseases/*etiology/prevention & control ; Physical Examination ; }, abstract = {An overview of published information on occupational cancer and recorded ongoing occupational cancer research in developing countries is presented. The main cancers reported, of possible occupational origin, are skin carcinoma, leukemia due to exposure to benzene, asbestos-caused mesothelioma, vinyl chloride-induced hepatic angiosarcoma, carcinoma of bilharzial urinary bladder, stomach cancer reportedly associated with nitrogen fertilizers, lung cancer of nickel smelters, and nasopharyngeal and pulmonary carcinoma in workers exposed to the dust of hard wood. The difficulties of developing efficient occupational cancer prevention are discussed. Some options are analyzed regarding legislative, technological, environmental, medical, administrative, and educational cancer control applicable under conditions of developing countries.}, } @article {pmid7349775, year = {1981}, author = {Lebovits, AH and Chahinian, AP and Gorzynski, JG and Holland, JC}, title = {Psychological aspects of asbestos-related mesothelioma and knowledge of high risk for cancer.}, journal = {Cancer detection and prevention}, volume = {4}, number = {1-4}, pages = {181-184}, pmid = {7349775}, issn = {0361-090X}, mesh = {Asbestos/*toxicity ; Health Education ; Humans ; Lung Neoplasms/etiology/*psychology ; Mesothelioma/etiology/*psychology ; Middle Aged ; Occupational Diseases/psychology ; Risk ; }, abstract = {Ten patients with a diagnosis of malignant mesothelioma were assessed for history of asbestos exposure, acquisition of and reactions to risk information, smoking behavior, and feelings about their disease and the asbestos industry. Mean age was 59 years; median span of time from diagnosis to interview was 10 months. Only two of seven patients with direct occupational asbestos exposure acquired risk information from a professional source. Lack of concern and denial are the reactions reported most frequently to risk information. Behavioral findings support the reported attitudinal reactions. None of the eight smokers in the sample stopped smoking after receiving increased risk information. Not a single patient increased his visits to a physician. Patients commonly expressed feelings of of being unlucky in reactions to the disease. Seven of the ten patients denied any feelings of anger toward the asbestos industry. These preliminary findings suggest the need for better information and education of high risk individuals.}, } @article {pmid7349771, year = {1981}, author = {Lee, PN}, title = {Assessing the risks of cancer.}, journal = {Cancer detection and prevention}, volume = {4}, number = {1-4}, pages = {15-23}, pmid = {7349771}, issn = {0361-090X}, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Animals ; Asbestos/toxicity ; Child ; Child, Preschool ; Dietary Fats/adverse effects ; Energy Intake ; Female ; Humans ; Infant ; Infant, Newborn ; Life Expectancy ; Male ; Mesothelioma/chemically induced ; Middle Aged ; Neoplasms/*etiology ; Occupational Diseases/chemically induced ; Risk ; }, abstract = {Recent claims that there is a growing epidemic of cancer caused by chemical and physical agents in the environment are shown to be weakly based. After smoking and diagnostic changes have been taken into account, trends in cancer mortality rates are not suggestive of any marked increases due to occupational factors. Estimates indicating that past occupational exposure to asbestos will cause large increases in cancer rates are shown to be markedly in error. Evidence that nutritional factors are likely to be much more important than occupational factors is summarized.}, } @article {pmid7349037, year = {1981}, author = {Woitowitz, HJ and Beierl, L and Rathgeb, M and Schmidt, K and Rödelsperger, K and Greven, U and Woitowitz, RH and Lange, HJ and Ulm, K}, title = {Asbestos-related diseases in the Federal Republic of Germany.}, journal = {American journal of industrial medicine}, volume = {2}, number = {1}, pages = {71-78}, doi = {10.1002/ajim.4700020112}, pmid = {7349037}, issn = {0271-3586}, mesh = {Adult ; Age Factors ; Aged ; Asbestosis/*epidemiology ; Germany, West ; Humans ; Lung Neoplasms/epidemiology ; Mesothelioma/epidemiology ; Middle Aged ; Risk ; Time Factors ; }, abstract = {Until recently, in the Federal Republic of Germany there has been a lack of epidemiological data on asbestos-related tumors. Only the numbers of occupational diseases accepted for compensation by the German industrial injuries insurance institutes (Berufsgenossenschaften) can be stated. These show, for 1979, 94 cases of asbestosis, 21 cases of asbestosis associated with lung cancer, and 34 cases of mesothelioma. Since 1972 employees exposed to asbestos dust have been included in a central register by the industrial injuries insurance institutes and are medically examined periodically. By December 31, 1979, 28,476 persons were registered. Of those, 6,582 were still being followed medically, although they were no longer working with asbestos dust exposure. In January 1, 1977, a prospective epidemiological study was started with these people who were formerly exposed to asbestos dust. Up to December 31, 1980, altogether 2,944 people were enrolled in the study. Besides several other enrollment criteria, the individual's permission was required to evaluate his personal data. Of the people enrolled, 85 had died by December 31, 1980. Even if five questionable cases of lung cancer are excluded (n = 80), the observed rates of about 43% tumours of all sites, with 15% lung cancer and 6% mesothelioma, seem to be comparable to the international epidemiological mortality pattern.}, } @article {pmid7337538, year = {1981}, author = {Konetzke, GW and Beck, B}, title = {[Risk factor asbestos (author's transl)].}, journal = {Archiv fur Geschwulstforschung}, volume = {51}, number = {7}, pages = {567-574}, pmid = {7337538}, issn = {0003-911X}, mesh = {Adolescent ; Adult ; Asbestos/*adverse effects ; Child ; Child, Preschool ; Humans ; Infant ; Mesothelioma/etiology ; Middle Aged ; Neoplasms/*etiology ; Occupational Diseases/*etiology ; Registries ; Risk ; }, abstract = {In the G.D.R. asbestos is used at a large industrial scale. The material is of interest for oncologists and industrial hygienists due to its fibrogenic and cancerogenic potencies. Both carcinomas of the respiratory organs and the rare malignant mesotheliomas are accepted as occupational diseases due to asbestos. In a retrospective study 915 cases of malignant mesotheliomas covered by the National Cancer Registry over a period of 6 years--all histologically established--were analysed. 36.7% originated from occupational handling of asbestos, 0.8% by non-occupational asbestos contacts. In another 9.1% of the cases asbestos may have been the underlying cause. 33.7% have had no asbestos contact; for 19.7% the data available were insufficient. Among the asbestos-containing materials used packing and insulating materials were prevailing in 47.7%, asbestos-containing talc in 19.6%. In 6.9% of the cases mesothelioma affection was due to wearing fire protective clothing. Different duration of exposure and especially long latency periods demonstrates difficulties interpreting the results concerning the relation between working conditions and illness. Primary (technical) prevention by reduction of asbestos dust emission, limited use of asbestos and lifelong monitoring of asbestos workers are necessary to reduce the tumour risk.}, } @article {pmid7329125, year = {1981}, author = {Argouarch, LP and Borel, B and Justum, AM and Davy, A and Verwaerde, JC and Valla, A}, title = {[Primary mesothelioma of the peritoneum and exposure to asbestos. Apropos of 6 cases].}, journal = {Medecine & chirurgie digestives}, volume = {10}, number = {7}, pages = {583-586}, pmid = {7329125}, issn = {0047-6412}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Female ; Humans ; Male ; Mesothelioma/diagnosis/*etiology ; Middle Aged ; Peritoneal Neoplasms/diagnosis/*etiology ; }, } @article {pmid7312760, year = {1981}, author = {Scarbonchi, J and Boutin, C and Cargnino, P and Scarbonchi-Efimieff, T}, title = {[Intrapleural talc in malignant pleural effusions (author's transl)].}, journal = {Le Poumon et le coeur}, volume = {37}, number = {5}, pages = {283-289}, pmid = {7312760}, issn = {0032-5821}, mesh = {Aged ; Female ; Humans ; Male ; Mesothelioma/complications ; Middle Aged ; Pleura ; Pleural Neoplasms/complications/secondary ; Pleurisy/etiology/*therapy ; Talc/administration & dosage/*therapeutic use ; }, abstract = {Intrapleural talc poudrage was carried out at the end of thoracoscopy in 77 patients after complete aspiration of fluid with uniform insufflation over the whole surface area of the pleura of 4 to 5 ml of pure talc, asbestos free. A continuous suction drain was left in place for 3 to 6 days. Amongst these patients, there were 57 cases of pleural effusion due to metastases and 20 mesotheliomas. A satisfactory result was obtained in 70 patients (91%). There were 7 failures. Fourteen mesotheliomas in which talc was used were compared with 14 further cases operated upon by pleurectomy. Both series were compared retrospectively in terms of age, sex, exposure to asbestos, histological type and the interval between the first symptom and treatment. In the talc series, there were 11 excellent results, 2 moderate and 1 nil. In the operated series there were 10 excellent results, 1 nil and 3 postoperative deaths. Survival of the patients was 395 +/- 55 days after the application of talc and 315 +/- 65 days after pleurectomy. There was thus a slight benefit in favour of the talc technique but this was not statistically significant. A figure of approximately 90% of satisfactory results is found in other series of the use of intrapleural talc published. This technique is thus effective and free of danger, and may be used in malignant effusions when techniques of local instillation of various substances and systemic chemotherapy have failed.}, } @article {pmid7312754, year = {1981}, author = {Martensson, G}, title = {Thoracoscopy in the diagnosis of malignant mesothelioma.}, journal = {Le Poumon et le coeur}, volume = {37}, number = {4}, pages = {249-251}, pmid = {7312754}, issn = {0032-5821}, mesh = {Asbestos/adverse effects ; Female ; Humans ; Hyaluronic Acid/analysis ; Male ; Mesothelioma/*diagnosis/etiology/metabolism ; Pleural Effusion/analysis ; Pleural Neoplasms/diagnosis/etiology ; *Thoracoscopy ; }, abstract = {Among 325 patients (95 women and 230 men) admitted to hospital for pleural effusion, 28 cases of malignant mesothelioma were found. In 22 of the 28 patients thoracoscopy was used to determine the course of the effusions. Thoracoscopy revealed the correct diagnosis in 19 of the 22 patients and thus gave far better results than cytological examination or hyaluronic acid determination on the pleural fluid.}, } @article {pmid7281500, year = {1981}, author = {Boon, ME and Posthuma, HS and Ruiter, DJ and von Andel, JG}, title = {Secreting peritoneal mesothelioma. Report of a case with cytological, ultrastructural, morphometric and histological studies.}, journal = {Virchows Archiv. A, Pathological anatomy and histology}, volume = {392}, number = {1}, pages = {33-44}, pmid = {7281500}, issn = {0340-1227}, mesh = {Adult ; Cell Differentiation ; Female ; Humans ; Mesothelioma/*metabolism/ultrastructure ; Microscopy, Electron ; Peritoneal Neoplasms/*metabolism/ultrastructure ; Pleural Neoplasms/secondary ; Prognosis ; }, abstract = {A 29 year old woman, living in an area with a high level of asbestos exposure, developed the clinical features of peritoneal mesothelioma. The quantitative cytological features differed from those of other mesotheliomas described in the literature in that the tumor cells had a large amount of vacuolated cytoplasm and an extremely low N/C ratio, resulting in a "benign" appearance. The ultrastructural study provided evidence for the production and accumulation of secretory products (mucolipids) by the tumor cells. Treatment with chemotherapy and radiation resulted in temporary remission, lasting for 20 months. However the patient then developed pulmonary involvement of the carcinomatosa a form and pleural tumors. The cytological pattern and the morphometric features of the metastatic floating malignant mesothelial cells in the pleural fluid closely resembled those of the primary peritoneal tumor. This case appears to be an example of secretory peritoneal mesothelioma with a bad prognosis, not withstanding the well-differentiated appearance of the tumor cells.}, } @article {pmid7220098, year = {1981}, author = {Chambers, HM and Henderson, DW}, title = {Test and teach. Number twenty-seven. Diagnosis: malignant pleural mesothelioma.}, journal = {Pathology}, volume = {13}, number = {1}, pages = {8-9, 159-61}, doi = {10.3109/00313028109086824}, pmid = {7220098}, issn = {0031-3025}, mesh = {Adult ; Asbestos/adverse effects ; Female ; Humans ; Male ; Mesothelioma/*diagnosis/pathology ; Neoplasm Invasiveness ; Pleura/pathology ; Pleural Neoplasms/*diagnosis ; }, } @article {pmid7032390, year = {1981}, author = {Davis, JM}, title = {The biological effects of mineral fibres.}, journal = {The Annals of occupational hygiene}, volume = {24}, number = {2}, pages = {227-234}, doi = {10.1093/annhyg/24.2.227}, pmid = {7032390}, issn = {0003-4878}, mesh = {Animals ; Asbestos/*adverse effects ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Particle Size ; }, } @article {pmid6790917, year = {1981}, author = {Brenner, J and Sordillo, PP and Magill, GB}, title = {Malignant mesothelioma in children: report of seven cases and review of the literature.}, journal = {Medical and pediatric oncology}, volume = {9}, number = {4}, pages = {367-373}, doi = {10.1002/mpo.2950090409}, pmid = {6790917}, issn = {0098-1532}, mesh = {Adolescent ; Brain Neoplasms/secondary ; Child ; Child, Preschool ; Female ; Humans ; Lung Neoplasms/surgery ; Male ; Mesothelioma/drug therapy/*pathology ; Methotrexate/therapeutic use ; Nitrogen Mustard Compounds/therapeutic use ; Pericardium/surgery ; Peritoneal Neoplasms/*pathology ; Pleural Neoplasms/*pathology ; Remission, Spontaneous ; Thiotepa/therapeutic use ; }, abstract = {Seven children with malignant mesothelioma have been seen at Memorial Hospital since 1953. In six, the origin was at the pleura and in one at the peritoneum. None of the patients related a history of exposure to asbestos. Two patients lived more than five years. The other five patients died within two years of the diagnosis. Distant metastases were seen in four of the patients, including three who had metastases to brain. Surgery or radiotherapy were not effective in controlling the disease in most of the patients. One patient had a complete response to a combination of Adriamycin, cyclophosphamide, and vincristine and has remained free of disease for 5 1/2 years. The seven cases are reviewed, as are the other 42 cases of malignant mesothelioma in children reported in the literature.}, } @article {pmid6453847, year = {1981}, author = {Myers, J}, title = {The social context of occupational disease: asbestos and South Africa.}, journal = {International journal of health services : planning, administration, evaluation}, volume = {11}, number = {2}, pages = {227-245}, doi = {10.2190/7WE1-WPCB-XYUT-PKBE}, pmid = {6453847}, issn = {0020-7314}, mesh = {Asbestos/*adverse effects ; Asbestosis/etiology ; Humans ; Labor Unions ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Mining/*economics ; Occupational Diseases/*economics/etiology ; Socioeconomic Factors ; South Africa ; United Kingdom ; Workers' Compensation ; }, abstract = {General issues of industrial health are raised in relation to the production of asbestos and asbestos-related diseases in South Africa., A historical analysis of these diseases and their control in Britain demonstrates some general problems of occupational diseases with long incubation periods and their implications for capital and labor. In order to understand the role of the research establishment, an attempt is made to situate the state in the conflict between capital and labor. The terms and weapons of this ideological arena are investigated. The South African situation is then discussed. Its evident weaknesses--the lack of statutory limits on exposure, capital's responsibility for monitoring exposure and health, the inefficiency of the state inspection, and the meagerness and racial disparities in compensation--are related to the weakness of organized labor. These weaknesses are linked to the movement of certain industrial processes, finally acknowledged as unsafe by most academic research, away from the developed countries. In these countries, the strength of labor and environmental organizations has caused a decline in capitalist productivity.}, } @article {pmid6268324, year = {1981}, author = {Monchaux, G and Bignon, J and Jaurand, MC and Lafuma, J and Sebastien, P and Masse, R and Hirsch, A and Goni, J}, title = {Mesotheliomas in rats following inoculation with acid-leached chrysotile asbestos and other mineral fibres.}, journal = {Carcinogenesis}, volume = {2}, number = {3}, pages = {229-236}, doi = {10.1093/carcin/2.3.229}, pmid = {6268324}, issn = {0143-3334}, mesh = {Animals ; Asbestos/*toxicity ; Asbestos, Serpentine ; Chemical Phenomena ; Chemistry ; Kinetics ; Male ; Mesothelioma/*etiology ; Minerals/*toxicity ; Neoplasms, Experimental/etiology ; Particle Size ; Rats ; }, abstract = {The carcinogenicity of untreated UICC chrysotile A, of acid (oxalic and hydrochloric)-leached UICC chrysotile A, of crocidolite and of JM 104 glass fibres has been studied by intrapleural injection into rats. This experiment, carried out on 304 animals, demonstrated that when more than 80% of the Mg had been leached from chrysotile fibres by either hydrochloric or oxalic acid, the proportion of pleural mesotheliomas was either nil or dramatically lower than that obtained with untreated chrysotile. The carcinogenic effect of crocidolite was higher than that of 43.7% oxalic acid-leached chrysotile. The proportion of mesotheliomas observed in animals injected with JM 104 glass fibres was similar to that in animals injected with fibres from which 63.8% had been leached with oxalic acid. These results indicate that with regard to the induction of pleural carcinogenicity by chrysotile fibres, not only size characteristics but also parameters such as chemical composition and physiochemical properties must intervene.}, } @article {pmid6266001, year = {1981}, author = {Inoue, A and Kawasaki, M and Kubo, H and Nakamura, N and Okumura, T and Ochiai, Y}, title = {[A case of malignant diffuse mesothelioma, bronchiolo-alveolar carcinoma and asbestosis occurred 30 years after exposure to asbestos (author's transl)].}, journal = {Kokyu to junkan. Respiration & circulation}, volume = {29}, number = {1}, pages = {93-99}, pmid = {6266001}, issn = {0452-3458}, mesh = {Adenocarcinoma, Bronchiolo-Alveolar/*etiology ; Asbestosis/*etiology ; Female ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Middle Aged ; Time Factors ; }, } @article {pmid7207653, year = {1980}, author = {Laros, CD}, title = {[Asbestos: report of the symposium of the same name held in memory of Prof. J. Swieringa].}, journal = {Nederlands tijdschrift voor geneeskunde}, volume = {124}, number = {52}, pages = {2224-2228}, pmid = {7207653}, issn = {0028-2162}, mesh = {Asbestos/*adverse effects ; Asbestosis/complications/*etiology/prevention & control ; Bronchial Neoplasms/etiology ; Gastrointestinal Neoplasms/etiology ; Humans ; Mesothelioma/etiology ; Pleural Neoplasms/etiology ; }, } @article {pmid7417959, year = {1980}, author = {McDonald, AD and McDonald, JC}, title = {Malignant mesothelioma in North America.}, journal = {Cancer}, volume = {46}, number = {7}, pages = {1650-1656}, doi = {10.1002/1097-0142(19801001)46:7<1650::aid-cncr2820460726>3.0.co;2-y}, pmid = {7417959}, issn = {0008-543X}, mesh = {Adolescent ; Adult ; Aged ; Asbestos/adverse effects ; Canada ; Female ; Humans ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Diseases/etiology ; Risk ; Sex Factors ; United States ; }, abstract = {Ascertainment, through 7,400 pathologists, of all fatal malignant mesothelial tumors in Canada (1960-75) and the U.S.A. (1972) gave a total of 668 cases (272 in 1972). In Canada, the annual number of male cases rose from about 17 in 1966 to 25 in 1972 but the number of female cases remained fairly steady at a much lower level. The annual incidence in North America in 1972 was estimated at 2.8 per million males and 0.7 per million females aged 15 years and over. Occupational histories were obtained "blind" for 480 of the 557 cases through 1972, and their matched controls; relative risks were as follows: insulation work, 46.0 asbestos production and manufacture, 6.1, heating trades (other than insulation) 4.4. For nearly half the male cases and for about 5% of female cases, the tumor could be attributed to occupational exposure to asbestos, of which a fifth were in shipyards. No indication was found of other possible causes (including man-made mineral fibers, tobacco smoking, or residence near zeolite deposits). Four subjects were men who had been employed in Quebec chrysotile mines and 3 were children of employees, but no other subject had lived in the mining area. The findings remain consistent with a much greater mesothelioma-producing potential for crocidolite and amosite than for chrysotile; however, further studies of factory workers exposed to chrysotile only are needed to confirm this. Mineral fiber analysis of lung tissue from patients and controls is in progress.}, } @article {pmid6931936, year = {1980}, author = {Blot, WJ and Morris, LE and Stroube, R and Tagnon, I and Fraumeni, JF}, title = {Lung and laryngeal cancers in relation to shipyard employment in coastal Virginia.}, journal = {Journal of the National Cancer Institute}, volume = {65}, number = {3}, pages = {571-575}, pmid = {6931936}, issn = {0027-8874}, mesh = {Adult ; Aged ; Asbestos/*toxicity ; Humans ; Laryngeal Neoplasms/*mortality ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; Middle Aged ; Occupational Diseases/*mortality ; Risk ; Ships ; *Smoking ; Virginia ; }, } @article {pmid6931931, year = {1980}, author = {Selikoff, IJ and Seidman, H and Hammond, EC}, title = {Mortality effects of cigarette smoking among amosite asbestos factory workers.}, journal = {Journal of the National Cancer Institute}, volume = {65}, number = {3}, pages = {507-513}, pmid = {6931931}, issn = {0027-8874}, mesh = {Adult ; Aged ; Air Pollutants/*toxicity ; Air Pollutants, Occupational/*toxicity ; Asbestos/*toxicity ; Dust ; Humans ; Lung Neoplasms/etiology/mortality ; Male ; Mesothelioma/mortality ; Middle Aged ; Neoplasms/etiology ; Pleural Neoplasms/mortality ; Prospective Studies ; Risk ; *Smoking ; }, } @article {pmid7426479, year = {1980}, author = {Arul, KJ and Holt, PF}, title = {Clearance of asbestos bodies from the lung: a personal view.}, journal = {British journal of industrial medicine}, volume = {37}, number = {3}, pages = {273-277}, pmid = {7426479}, issn = {0007-1072}, mesh = {Adult ; Aged ; Asbestos/adverse effects/*metabolism ; Female ; Hemosiderin/metabolism ; Humans ; Lung/*metabolism/ultrastructure ; Lung Neoplasms/etiology/*metabolism/ultrastructure ; Male ; Mesothelioma/etiology/*metabolism/ultrastructure ; Microscopy, Electron ; Middle Aged ; Occupational Diseases/etiology/*metabolism/pathology ; }, abstract = {In histological sections asbestos bodies in human lungs may be either transparent, yellow, strongly Perls-positive structures as described in published reports, or opaque, black structures, the ferroprotein coating having been converted into haemosiderin. The transparent asbestos bodies fragment into segments; the black asbestos bodies disintegrate into a mass of haemosiderin granules that accumulate as dense deposits, particularly near to blood vessels. The presence of haemosiderin granules indicates that asbestos bodies have broken down. When a patient has died with a mesothelioma there is little evidence of phagocytic activity in many areas of the lung. When exposure to asbestos ceased many years before a mesothelioma developed there may be few recognisable asbestos bodies remaining in the lung.}, } @article {pmid7053009, year = {1980}, author = {Anyanwu, CH and Udekwu, FA}, title = {Clinical aspects of pulmonary and pleural carcinoma in Nigeria.}, journal = {Medical journal of Zambia}, volume = {14}, number = {5}, pages = {83-89}, pmid = {7053009}, issn = {0047-651X}, mesh = {Adolescent ; Adult ; Aged ; Child, Preschool ; Female ; Humans ; Lung Neoplasms/etiology/*pathology/secondary/therapy ; Male ; Middle Aged ; Pleural Neoplasms/etiology/*pathology/secondary/therapy ; Smoking ; }, abstract = {Carcinoma of the lung may not be uncommon in Nigeria and other parts of tropical Africa. Twenty-seven cases of pulmonary and pleural carcinoma seen at UNTH Enugu, are reviewed; 20 were primary and 7 were secondary. The 20 patients with primary carcinoma were aged 35-75 years (mean 51.8 years); there were 14 males and 6 females. Cigarette smoking was the possible aetiological factor in 10 cases while exposure to asbestos products was elicited in a case of mesothelioma. Massive pleura effusion was present in 60% of cases. Different histological cell types were represented but squamous cell and adenocarcinoma were predominating. Resection could be achieved in only 3 cases. Mean survival period was 103.5 days for the primary carcinoma, and 80.8 days for the secondary carcinomas. With increasing industrialisation, atmospheric pollution and cigarette smoking in Nigeria, the incidence and problems of bronchopulmonary carcinoma would be expected to rise.}, } @article {pmid6155613, year = {1980}, author = {Antman, KH}, title = {Current concepts: malignant mesothelioma.}, journal = {The New England journal of medicine}, volume = {303}, number = {4}, pages = {200-202}, doi = {10.1056/NEJM198007243030407}, pmid = {6155613}, issn = {0028-4793}, mesh = {Adult ; Aged ; Alkylating Agents/therapeutic use ; Asbestos/toxicity ; Doxorubicin/therapeutic use ; Humans ; *Mesothelioma/diagnosis/epidemiology/pathology/therapy ; Middle Aged ; Occupational Diseases/epidemiology ; Palliative Care ; Peritoneal Neoplasms/pathology ; Pleura/surgery ; Pleural Neoplasms/pathology ; Pneumonectomy ; Prognosis ; Thoracic Surgery ; }, } @article {pmid7415839, year = {1980}, author = {Okumura, T and Okada, M and Tsuji, M and Inoue, A and Ochiai, Y}, title = {Mesothelioma with lung cancer complicating asbestosis.}, journal = {Acta pathologica japonica}, volume = {30}, number = {4}, pages = {579-590}, doi = {10.1111/j.1440-1827.1980.tb01353.x}, pmid = {7415839}, issn = {0001-6632}, mesh = {Asbestosis/*complications ; Female ; Humans ; Lung Neoplasms/*etiology/ultrastructure ; Mesothelioma/*etiology/ultrastructure ; Middle Aged ; }, abstract = {The patient had been employed in an asbestos factory for four years from the age of 16. Five years ago, she complained of sputum and cough, and she was treated for chronic bronchitis. From March, 1977, when she was 53 years old, hydrothorax and ascites increased, her weight decreased and she was hospitalized for cachexia. The clinical diagnosis of malignant diffuse mesothelioma was made on the presence of atypical cells in the effusions. Atypical cells showed a positive colloidal iron staining test and positive hyaluronidase digestion test. Asbestos bodies were found in the sputum. The patient died on February 1978. Postmortem confirmed asbestosia and mesothelioma which was scattered over the pleura, pericardial sac, diaphragma, peritoneum and pancreas. In addition, bronchiolo-alveolar cell type lung cancer was found localized in the lower lobe of the left lung. The electron beam diffraction disclosed the asbestos as amosite (brown asbestos).}, } @article {pmid7416594, year = {1980}, author = {Clark, TC and Harrington, VA and Asta, J and Morgan, WK and Sargent, EN}, title = {Respiratory effects of exposure to dust in taconite mining and processing.}, journal = {The American review of respiratory disease}, volume = {121}, number = {6}, pages = {959-966}, doi = {10.1164/arrd.1980.121.6.959}, pmid = {7416594}, issn = {0003-0805}, mesh = {Adult ; *Dust ; Environmental Exposure ; Humans ; Iron/*toxicity ; Lung/diagnostic imaging ; Male ; Middle Aged ; Minerals/*toxicity ; *Mining ; Occupational Diseases/*etiology ; Radiography ; Respiratory Function Tests ; Respiratory Tract Diseases/*etiology ; *Silicates ; Silicosis/etiology ; Smoking ; Time Factors ; }, abstract = {Taconite is a low-grade iron ore consisting of iron, quartz, and numerous silicates. Taconite from the eastern tip of the Mesabi Iron Range contains the amphibole silicate cummingtonite-grunerite, which is a mineral relative of amosite asbestos. In the present study, data were collected from 249 men with 20 or more years of exposure to taconite dust and 86 men without history of intimate exposure to taconite dust. Bronchitic symptoms and impairment of expiratory flow correlated significantly with history of cigarette smoking, but not with exposure to dust. Chest radiographs revealed three cases of possible silicosis. No case of definite interstitial fibrosis, ill-defined diaphragm, pleural calcification, or mesothelioma was found. We conclude that (1) cigarette smoking is significantly correlated with bronchitic symptoms and impairment of expiratory flow; (2) taconite workers are at risk of silicosis; (3) if dust containing cummingtonite-grunerite has biologic activity comparable to that of dust from asbestos, it is not evident after 20 years of low-level exposure.}, } @article {pmid7412036, year = {1980}, author = {Hasegawa, H and Kikuchi, F and Goto, T and Ueda, A and Matsushita, K and Oyagi, S}, title = {[A case of malignant pleural mesothelioma with calcified diaphragmatic pleural plaques following asbestos exposure (author's transl)].}, journal = {Nihon Kyobu Shikkan Gakkai zasshi}, volume = {18}, number = {6}, pages = {417-421}, pmid = {7412036}, issn = {0301-1542}, mesh = {Asbestosis/*complications ; Calcinosis/*etiology ; Humans ; Male ; Mesothelioma/*etiology ; Middle Aged ; Pleural Neoplasms/*etiology ; }, } @article {pmid7001808, year = {1980}, author = {Brand, G and Brand, I}, title = {[Investigations and review of literature relating to carcinogenesis. I. Communication: Cancer from asbestos, schistosomiasis, and cicatrization (author's transl)].}, journal = {Zentralblatt fur Bakteriologie, Mikrobiologie und Hygiene. 1. Abt. Originale B, Hygiene}, volume = {171}, number = {1}, pages = {1-17}, pmid = {7001808}, issn = {0174-3015}, support = {CA 10712/CA/NCI NIH HHS/United States ; ES 02101/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Asbestos/*adverse effects ; Asbestosis/complications ; Cicatrix/*complications ; Disease Models, Animal ; Guinea Pigs ; Humans ; Lung Neoplasms/etiology ; Mice ; Neoplasms/*etiology ; Precancerous Conditions ; Rats ; Schistosomiasis/*complications ; Smoking ; Tuberculosis, Pulmonary/complications ; }, abstract = {This review covers the following aspects: Cancer associated with asbestos and other fibers: Epidemiology. - Cancer types and location (mesothelioma; bronchogenic carcinoma; cancer of the upper respiratory tract; abdominal cancer). - Experimental asbestos cancer. - Other kinds of fibers and cancer (wool and cotton; glass; talc; others). - Cancer determining or influencing factors (individual predisposition; species susceptibility; type of material; shape and size of fibers; smoking). - Preneoplastic signs in man (fibrosis; ferruginous bodies; pleural plaques; milky spots). - Preneoplastic development in animals. - Fiber effects on cell cultures (macrophages; fibroblasts). Cancer associated with schistosomiasis: Epidemiology. - Patient age and cancer latency. - Pathology. - Foreign body reaction and preneoplastic development. Scar cancer. Foreign body cancer: In man. - Experimental (species differences in susceptibility; individual genetic differences in tumor incidence and latency; influence of sex, age, nutrition; tumor histopathology and ultrastructure; tumor growth, invasiveness, metastases, transplantability, immunology; search for tumor viruses). - Properties of foreign body materials in relation to tumorigenicity (chemical and physical properties; size and shape; surface properties; porosity). - Investigations and findings concerning the origin of foreign body sarcomas (the foreign body reaction; search for foci of tumor origin; an analytical method; monoclonal tumor origin; heterogenicity of carcinogenic events; surface dependency; identification of originator cells; time and location of the emergence of tumor originator cells; the carcinogenic initiation event; surface-independent and dependent preneoplastic maturation; the carcinogenic role of the foreign body). - Earlier hypotheses and theories in the light of new experimental findings. The results of experimental foreign body tumorigenesis in relation to foreign body-, asbestos-, schistosomiasis-, and scar-cancer in man. (Common factors of promotion; differences regarding induction mechanisms, cells of origin, latencies, frequencies; immune defense). Consequences for prevention: Asbestos cancer. - Fiber cancer. - Schistosomiasis cancer. - Foreign body cancer (assessing the peril in man; testing of materials for carcinogenicity; recommendations).}, } @article {pmid6252922, year = {1980}, author = {Wagner, JC and Hill, RJ and Berry, G and Wagner, MM}, title = {Treatments affecting the rate of asbestos-induced mesotheliomas.}, journal = {British journal of cancer}, volume = {41}, number = {6}, pages = {918-922}, pmid = {6252922}, issn = {0007-0920}, mesh = {Animals ; *Asbestos ; BCG Vaccine ; Carrageenan/therapeutic use ; Mesothelioma/etiology/*prevention & control ; Neoplasms, Experimental/etiology/prevention & control ; Pleural Neoplasms/etiology/*prevention & control ; Rats ; Silicon Dioxide/therapeutic use ; Talc/therapeutic use ; }, abstract = {256 Wistar rats received a single injection into the right pleural cavity of UICC crocidolite in order to induce mesotheliomas. They were then given right intrapleural injectons of BCG, crystalline silica, talc, carrageenan or saline (as a control). There was no significant change in the mesothelioma rate in the rats exposed to BCG, silica or talc, but there was a 3-fold increase in mesothelioma incidence in the group injected with carrageenan.}, } @article {pmid7383193, year = {1980}, author = {Ouderkerk, J and Roepke, WJ and Hohmann, FR and Hulst, SG}, title = {[2 patients with peritoneal mesothelioma].}, journal = {Nederlands tijdschrift voor geneeskunde}, volume = {124}, number = {20}, pages = {783-786}, pmid = {7383193}, issn = {0028-2162}, mesh = {Aged ; Asbestos/*adverse effects ; Humans ; Male ; Mesothelioma/etiology/*pathology ; Middle Aged ; Occupational Diseases/etiology ; Peritoneal Neoplasms/etiology/*pathology ; Time Factors ; }, } @article {pmid7428261, year = {1980}, author = {Young, JR and Reddy, ER}, title = {Peritoneal mesothelioma.}, journal = {Clinical radiology}, volume = {31}, number = {3}, pages = {243-247}, doi = {10.1016/s0009-9260(80)80208-x}, pmid = {7428261}, issn = {0009-9260}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Female ; Humans ; Intestines/diagnostic imaging ; Male ; Mesothelioma/*diagnostic imaging ; Middle Aged ; Occupational Diseases/diagnostic imaging/etiology ; Peritoneal Neoplasms/*diagnostic imaging ; Radiography ; }, abstract = {The clinical and radiological features of peritoneal mesothelioma in four patients with an industrial history of asbestos exposure are described. The radiological features of intestinal obstruction, soft tissue masses and displacement and infiltration of bowel are stressed. A normal chest radiograph does not exclude the diagnosis. More sensitive diagnostic imaging and perhaps the use of laparoscopy may help to improve the accuracy of pre-mortem diagnosis.}, } @article {pmid7426462, year = {1980}, author = {Axelsson, G and Rylander, R and Schmidt, A}, title = {Mortality and incidence of tumours among ferrochromium workers.}, journal = {British journal of industrial medicine}, volume = {37}, number = {2}, pages = {121-127}, pmid = {7426462}, issn = {0007-1072}, mesh = {Adolescent ; Adult ; Aged ; Chromium/*adverse effects ; Humans ; Male ; Middle Aged ; Neoplasms/chemically induced/epidemiology/*mortality ; Occupational Diseases/chemically induced/epidemiology/*mortality ; Respiratory Tract Neoplasms/chemically induced/epidemiology/mortality ; Sweden ; Time Factors ; }, abstract = {An investigation was carried out to determine the cause of death and the incidence of tumours among 1932 workers in a ferrochromium plant in Sweden. The workers had been exposed mainly to metallic and trivalent chromium (Cr[3+]); hexavalent chromium (Cr[6+]) was also present in certain working operations. The population was defined as all men employed at the plant for at least one year during 1930-75, and were classified according to their occupation within the industry. The causes of death were initially obtained from parish registers. For deaths occuring between 1951 and 1975, death certificates were collected from the National Central Bureau of Statistics. Data on the incidence of cancer during 1958-75 were obtained from the Swedish National Cancer Registry. Expected death rates and incidence of tumours were calculated, based on the rates for the county in which the factory was situated. The total number of deaths from tumours was less than expected (69 versus 76·7). Five cases of respiratory cancer were found, against an expected 7·2. Among maintenance workers, an increased death rate from all tumours and an increased number of respiratory tumours were found. Two of the latter were mesotheliomas and could be connected with asbestos exposure. No increase was found for respiratory tumours among the heavily exposed workers at the arc-furnaces; one case of mesothelioma was found in this group.}, } @article {pmid7379488, year = {1980}, author = {Murphy, R}, title = {Asbestos related disease: difficulties in diagnosing occupationally related illness.}, journal = {Comprehensive therapy}, volume = {6}, number = {5}, pages = {6-13}, pmid = {7379488}, issn = {0098-8243}, mesh = {Asbestos/*toxicity ; Asbestosis/*diagnosis/diagnostic imaging ; Diagnosis, Differential ; Diffusion ; Dyspnea/etiology ; Heart Failure/diagnosis ; Humans ; Lung/diagnostic imaging/pathology ; Lung Neoplasms/etiology ; Mesothelioma/epidemiology/etiology ; Pleural Diseases/diagnosis/etiology ; Pulmonary Fibrosis/etiology ; Radiography ; Smoking/complications ; United States ; Vital Capacity ; }, } @article {pmid7379039, year = {1980}, author = {Risberg, B and Nickels, J and Wågermark, J}, title = {Familial clustering of malignant mesothelioma.}, journal = {Cancer}, volume = {45}, number = {9}, pages = {2422-2427}, doi = {10.1002/1097-0142(19800501)45:9<2422::aid-cncr2820450930>3.0.co;2-z}, pmid = {7379039}, issn = {0008-543X}, mesh = {*Asbestos ; Environmental Exposure ; Female ; Humans ; Lung Neoplasms/etiology/*genetics/pathology ; Male ; Mesothelioma/etiology/*genetics/pathology ; Microscopy, Electron ; Middle Aged ; Pedigree ; Peritoneal Neoplasms/genetics ; *Smoking ; }, abstract = {A family with a remarkable aggregation of malignant mesothelioma is described. The father, 3 brothers, and a sister all died of the condition. The family and epidemiologic histories are reviewed. Random occupational asbestos exposure in the building industry probably occurred in 4 of the 5 cases. All of the patients were smokers. There is a low incidence of malignant mesothelioma in the area where they resided. These observations suggest that over and above the smoking and asbestos exposure, heredity may be an important predisposing factor in the genesis of this tumor.}, } @article {pmid6103109, year = {1980}, author = {Acheson, ED and Gardner, MJ}, title = {Possible synergism between chrysotile and amphibole asbestos.}, journal = {Lancet (London, England)}, volume = {1}, number = {8170}, pages = {706}, pmid = {6103109}, issn = {0140-6736}, mesh = {Asbestos/*adverse effects ; Asbestos, Amphibole ; Asbestos, Serpentine ; Drug Synergism ; Humans ; Mesothelioma/*etiology ; Pleural Neoplasms/*etiology ; Silicon Dioxide/*adverse effects ; }, } @article {pmid6244076, year = {1980}, author = {Donham, KJ and Berg, JW and Will, LA and Leininger, JR}, title = {The effects of long-term ingestion of asbestos on the colon of F344 rats.}, journal = {Cancer}, volume = {45}, number = {5 Suppl}, pages = {1073-1084}, doi = {10.1002/1097-0142(19800315)45:5+<1073::aid-cncr2820451308>3.0.co;2-w}, pmid = {6244076}, issn = {0008-543X}, mesh = {Adenocarcinoma/etiology ; Adenoma/etiology ; Animals ; Asbestos/metabolism/*toxicity ; Colon/metabolism ; Colonic Neoplasms/*etiology ; Cyclic AMP/metabolism ; Cyclic GMP/metabolism ; Dietary Fiber ; Female ; Male ; Mesothelioma/etiology ; Neoplasms, Experimental/etiology ; Rats ; Rats, Inbred F344 ; Time Factors ; }, abstract = {Weanling F344 rats, which were fed a diet containing 10% chrysotile (B), were studied over their life-time to determine the effects of ingested asbestos on the colon. Control groups consisted of rats fed a diet containing a 10% nonnutritive cellulose or a standard laboratory rat diet. The pathological findings in the colons of 501 rats (189 on asbestos diet, 197 on fiber control diet, and 115 on standard control diet), are reported here. Epithelial tumors of the colon (eight adenocarcinomas and one adenoma) were found in nine of the rats on study. Four of the tumors were in asbestos-fed rats, two tumors were found in the non-nutritive cellulose controls, and three tumors were found in the standard laboratory rat diet controls. The probability (based on actuarial analysis) of developing adenoma or adenocarcinomas during the 32 months of the study were 7.4% for the asbestos-fed group, 3.5% for the fiber control diet and 4.0% on the standard control diet. In addition, one malignant mesothelioma of the type induced by intraperitoneally administered asbestos was found in the asbestos-fed group. Non-neoplastic lesions of the colon were also evaluated. The cumulative risk for development of any colon-associated lesion (non-neoplastic plus neoplastic lesions) was greatest for asbestos-fed rats (17.9%), compared to 13.6% for those fed the fiber control diet and 8.2% for those fed the standard control diet. The colon tissue levels of adenosine, 3'-5'-cyclic monophosphate (cAMP) were significantly lower in the animals fed asbestos compared to the control diets. Chrysotile fibers were seen by electronmicroscopy (e.m.) in six of ten ashed colon specimens of rats fed the asbestos diet. Although the differences in numbers of tumors between the animals fed asbestos and the controls were not statistically significant at the 5% level, we felt that the combination of observations including 1) evidence of increased probability of asbestos-fed animals to develop colon lesions in general; 2) evidence of a special type of mesothelioma in rats fed asbestos; 3) evidence for a cell regulator defect (lowered cAMP levels) in colon tissues of animals fed asbestos; and 4) evidence for asbestos fiber penetration of the colonic mucosa (e.m. studies) suggest that ingested asbestos is not inert in the colon.}, } @article {pmid7428580, year = {1980}, author = {Zhang, Z}, title = {[Pleural mesothelioma and asbestos (author's transl)].}, journal = {Zhonghua jie he he hu xi xi ji bing za zhi = Chinese journal of tuberculosis and respiratory diseases}, volume = {3}, number = {1}, pages = {52-54}, pmid = {7428580}, issn = {0253-2689}, mesh = {Adolescent ; Adult ; Aged ; Asbestosis/*complications ; Female ; Humans ; Male ; Mesothelioma/*etiology ; Pleural Neoplasms/*etiology ; }, } @article {pmid7361805, year = {1980}, author = {Antman, KH and Blum, RH and Greenberger, JS and Flowerdew, G and Skarin, AT and Canellos, GP}, title = {Multimodality therapy for malignant mesothelioma based on a study of natural history.}, journal = {The American journal of medicine}, volume = {68}, number = {3}, pages = {356-362}, doi = {10.1016/0002-9343(80)90103-5}, pmid = {7361805}, issn = {0002-9343}, mesh = {Aged ; Antineoplastic Agents/administration & dosage ; Asbestos ; Doxorubicin/administration & dosage ; Drug Therapy, Combination ; Environmental Exposure ; Female ; Humans ; Male ; Mesothelioma/diagnosis/mortality/*therapy ; Middle Aged ; Peritoneal Neoplasms/diagnosis/mortality/*therapy ; Pleural Neoplasms/diagnosis/mortality/*therapy ; Prognosis ; Radiotherapy Dosage ; Smoking ; }, } @article {pmid6993044, year = {1980}, author = {Pierce, R and Turner-Warwick, M}, title = {Skin tests with tuberculin (PPD) Candida albicans and Trichophyton spp. in cryptogenic fibrosing alveolitis and asbestos related lung disease.}, journal = {Clinical allergy}, volume = {10}, number = {2}, pages = {229-237}, doi = {10.1111/j.1365-2222.1980.tb02101.x}, pmid = {6993044}, issn = {0009-9090}, mesh = {Adolescent ; Adult ; Aged ; Asbestosis/*immunology ; Candida albicans/immunology ; Humans ; Hypersensitivity, Delayed/immunology ; *Immunity, Cellular ; Lung Diseases/immunology ; Lung Neoplasms/immunology ; Mesothelioma/immunology ; Middle Aged ; Prospective Studies ; Pulmonary Fibrosis/*immunology ; Skin Tests ; Trichophyton/immunology ; Tuberculin Test ; }, abstract = {Delayed skin hypersensitivity responses were elicited in patients with cryptogenic fibrosing alveolitis (CFA) (twenty-eight), asbestosis (eight), mesothelioma (eight) and a "control" group, having miscellaneous lung diseases not normally believed to be associated with T cell deficiency (twenty). Three antigens, Candida albicans, trichophyton and purified protein derivative (PPD) in a range of doses were used. There was no evidence of impaired cellular immunity in CFA or in mesothelioma, indeed there was a significantly increased frequency of reactions to PPD in both of these conditions (P less than 0.05 and P less than 0.01 respectively). There was, however, a trend of decreased responsiveness in the group with asbestosis. The dosage regimen used rarely gave completely negative results (only one of thirty-two completed tests), and may provide a basis for a simple and standard regimen for screening patients suspected of having defective T cell responses.}, } @article {pmid7374543, year = {1980}, author = {Ferguson, D and Ng, T}, title = {Australian mesothelioma register.}, journal = {The Medical journal of Australia}, volume = {1}, number = {4}, pages = {150-152}, doi = {10.5694/j.1326-5377.1980.tb134730.x}, pmid = {7374543}, issn = {0025-729X}, mesh = {Asbestos/adverse effects ; Australia ; Environmental Exposure ; Humans ; Medical History Taking ; Medical Records ; *Mesothelioma/etiology ; Organization and Administration ; *Registries ; }, } @article {pmid7374542, year = {1980}, author = {Ferguson, D and Ng, T}, title = {Mesothelioma--ignorance is not bliss.}, journal = {The Medical journal of Australia}, volume = {1}, number = {4}, pages = {150}, pmid = {7374542}, issn = {0025-729X}, mesh = {Asbestos/adverse effects ; Australia ; Humans ; *Mesothelioma/etiology ; *Registries ; }, } @article {pmid7389690, year = {1980}, author = {Lipkin, LE}, title = {Cellular effects of asbestos and other fibers: correlations with in vivo induction of pleural sarcoma.}, journal = {Environmental health perspectives}, volume = {34}, number = {}, pages = {91-102}, pmid = {7389690}, issn = {0091-6765}, mesh = {Aluminum/toxicity ; *Aluminum Hydroxide ; Aluminum Oxide/toxicity ; Animals ; Asbestos/*toxicity ; Carbonates/toxicity ; Cell Count ; Cell Line ; Glass ; Macrophages/cytology/*drug effects ; Mice ; Pleural Neoplasms/*etiology ; Sarcoma/*etiology ; Titanium/toxicity ; }, abstract = {The phenomenon of fiber-induced cytotoxicity to P388D1 macrophagelike cells has been demonstrated to parallel (thus far without exception) the probability that the fiber will induce a pleural sarcoma (mesothelioma) in rats. This startling parallel in both cases seems to be essentially independent of the chemical nature of the fiber and correlates best with the presence of fibers greater than 8 micrometers in length and fibers with diameters in the range 0.5 to 1.0 micrometer (Stanton Hypothesis). In both systems evidence has been produced which cast strong doubts on any role played by absorbed (or adherent) impurities. The existence of multiple physical forms of the same chemical moiety (aluminum oxide, dihydroxy-sodium aluminum carbonate, borosilicate glass, etc.,) provides additional test material for the chemical independence corollary. The similar, cytotoxic or sarcomatogenous behavior of chemically different materials (e.g. amosite, chrysotile, aluminum oxide) exhibits the necessary converse argument. As long as the fiber size-shape dependency effect was limited to whole animal phenomena, such as tumor induction, one could make implicitly what were essentially statistical or probabilistic inferences involving transport and/or distribution of fibers to account for the physical effect. The demonstration of strict parallelism at the cellular level in vitro suggests the possibility that in the case of durable fiber toxicology we are dealing with a form of cell-solid interaction in which physical properties for which we have as yet no known receptors play a prominent role.}, } @article {pmid7389687, year = {1980}, author = {Frank, AL}, title = {Clinical observations following asbestos exposure.}, journal = {Environmental health perspectives}, volume = {34}, number = {}, pages = {27-30}, pmid = {7389687}, issn = {0091-6765}, mesh = {Asbestos/*adverse effects ; Asbestosis/diagnosis ; Humans ; Neoplasms/diagnosis/etiology ; Occupational Diseases/diagnosis/etiology ; }, abstract = {There is a spectrum of clinical entities following occupational exposure to asbestos. Methods of evaluation for these problems are reviewed. Nonmalignant clinical conditions include asbestos warts, asbestos bodies, parenchymal fibrosis (asbestosis), pleural fibrosis and calcification, and benign asbestotic pleural effusion. Asbestosis, though a benign process, is a significant cause of death. Malignant conditions associated with asbestos exposure include lung cancer, accounting for about 20% of all deaths among insulation workers and significantly related to cigarette smoking. The lung cancers tend to occur more frequently in the lower lobes and are more peripheral. Pleural and peritoneal mesothelioma and some excesses in gastrointestinal cancers are found with asbestos exposure, although these are not related to cigarette smoking. Increased rates of malignancy first become significant after 20 years from onset of exposure and are also related to duration of exposure. Difficulties with the use of death certificate data are reviewed.}, } @article {pmid7370190, year = {1980}, author = {Morgan, A and Holmes, A}, title = {Concentrations and dimensions of coated and uncoated asbestos fibres in the human lung.}, journal = {British journal of industrial medicine}, volume = {37}, number = {1}, pages = {25-32}, pmid = {7370190}, issn = {0007-1072}, mesh = {Adult ; Aged ; Asbestos/*analysis ; Female ; Humans ; Lung/*analysis/ultrastructure ; Lung Neoplasms/analysis/ultrastructure ; Male ; Mesothelioma/analysis/ultrastructure ; Microscopy, Electron ; Middle Aged ; Occupational Diseases/metabolism/pathology ; Particle Size ; }, abstract = {Concentrations and length distributions of uncoated and coated amphibole-type fibres in samples of human lung taken at necropsy were measured by optical microscopy using the membrane filter technique that enables fibres with diameters down to about 0.2 micron to be detected. The subjects included 10 who died with mesothelial tumours, three with lung cancer, and eight of other causes. Measurements of fibre concentrations are compared with those of other workers. It can be deduced from the length distributions that fibres less than 5 microns long are cleared from the lung more efficiently than longer ones. The clearance of short fibres appears to be inhibited in subjects with asbestosis, however. The length distributions of uncoated and coated fibres were dissimilar. In general, few fibres less than 10 microns in length were coated and few greater than 40 microns in length were uncoated. The probability of a fibre of given length, however, becoming coated varied considerably from subject to subject. Possible reasons for this are discussed.}, } @article {pmid7370189, year = {1980}, author = {McDonald, JC and Liddell, FD and Gibbs, GW and Eyssen, GE and McDonald, AD}, title = {Dust exposure and mortality in chrysotile mining, 1910-75.}, journal = {British journal of industrial medicine}, volume = {37}, number = {1}, pages = {11-24}, pmid = {7370189}, issn = {0007-1072}, mesh = {Accidents ; Aged ; Asbestos/*adverse effects ; Asbestosis/mortality ; Cerebrovascular Disorders/mortality ; *Dust ; Employment ; Environmental Exposure ; Female ; Follow-Up Studies ; Heart Diseases/mortality ; Humans ; Lung Neoplasms/mortality ; Male ; Middle Aged ; *Mining ; Neoplasms/mortality ; Occupational Diseases/*mortality ; Quebec ; Respiration Disorders/mortality ; Smoking/complications ; Time Factors ; }, abstract = {We report a further follow-up of a birth cohort of 11 379 workers exposed to chrysotile. The cohort consisted of 10 939 men and 440 women, born 1891-1920, who had worked for at least a month in the mines and mills of Asbestos and Thetford Mines in Quebec. For all subjects, length of service and estimates of accumulated dust exposure were obtained, with a smoking history for the vast majority. Three methods of analysis, two based on the "man-years" methods, the other a "case-and-multiple-controls" approach, gave results consistent with one another and with previous analyses. By the end of 1975, 4463 men and 84 women had died. Among men, the overall excess mortality, 1926-75 was 2% at Asbestos and 10% at Thetford Mines, much the dustier region. The women, mostly employed at Asbestos, had a standardised mortality ratio (SMR) all causes, 1936-75) of 0.90. Analysis of deaths 20 years or more after first employment showed that in men with short service (less than five years) there was no discernible correlation with dust exposure. Among men employed at least 20 years, there were clear excesses in those exposed to the heaviest dust concentrations. Reanalysis in terms of exposure to age 45 showed definite and consistent trends for SMRs for total mortality, for lung cancer, and for pneumoconiosis to be higher the heavier the exposure. The response to increasing dose was effectively linear for lung cancer and for pneumoconiosis. Lung cancer deaths occurred in non-smokers, and showed a greater increase of incidence with increasing exposure than did lung cancer in smokers, but there was insufficient evidence to distinguish between multiplicative and additive risk models. There were no excess deaths from laryngeal cancer, but a clear association with smoking. Ten men and one woman died from pleural mesothelioma. If the only subjects studied had been the 1904 men with at least 20 years' employment in the lower dust concentrations, averaging 6.6 million particles per cubic foot (or about 20 fibres/cc), excess mortality would not have been considered statistically significant, except for pneumoconiosis. The inability of such a large epidemiological survey to detect increased risk at what, today, are considered unacceptable dust concentrations, and the consequent importance of exposure-response models are therefore emphasised.}, } @article {pmid7353405, year = {1980}, author = {Auerbach, O and Conston, AS and Garfinkel, L and Parks, VR and Kaslow, HD and Hammond, EC}, title = {Presence of asbestos bodies in organs other than the lung.}, journal = {Chest}, volume = {77}, number = {2}, pages = {133-137}, doi = {10.1378/chest.77.2.133}, pmid = {7353405}, issn = {0012-3692}, mesh = {Aged ; Asbestos/*metabolism ; Asbestosis/metabolism ; Environmental Exposure ; Female ; Histocytochemistry ; Humans ; Kidney/metabolism ; Lung/*metabolism ; Male ; Middle Aged ; Myocardium/metabolism ; Occupations ; Pancreas/metabolism ; Spleen/metabolism ; Tissue Distribution ; }, abstract = {This study was designed to test the hypothesis that subjects with many asbestos bodies in their lungs at autopsy would also have asbestos bodies in various other organs. The subjects included 19 cases with diagnosis of asbestosis at death (two of these had mesothelioma, five had lung cancer) and 18 with pleural plaques but not asbestosis. Occupational histories were obtained from relatives. In subjects occupationally exposed to asbestos, large numbers of asbestos bodies were found in the lungs, and in most of these, asbestos bodies were found in many of the other organs examined. In the 18 cases with only pleural plaques found at autopsy, considerably fewer asbestos bodies were found in the lungs. The number of other organs with one or more asbestos bodies ranged from 32 percent to 62 percent of the sites examined. The findings seem to confirm the hypothesis of the study.}, } @article {pmid6993202, year = {1980}, author = {Kannerstein, M and Churg, J}, title = {Mesothelioma in man and experimental animals.}, journal = {Environmental health perspectives}, volume = {34}, number = {}, pages = {31-36}, pmid = {6993202}, issn = {0091-6765}, mesh = {Animals ; Asbestos/*adverse effects ; Disease Models, Animal ; Humans ; Lung/pathology ; Mesothelioma/diagnosis/*etiology/pathology ; Particle Size ; Peritoneal Neoplasms/diagnosis/etiology ; Pleural Neoplasms/diagnosis/etiology ; }, abstract = {Asbestos has been established as the cause of most cases of diffuse malignant mesothelioma occurring in the industrialized world. The morphology of mesothelioma may be complex, and the employment of chemical, histochemical and ultrastructural studies are often helpful in identification. Diagnostic difficulties may to some degree blur the extent of its prevalence and reliance on exposure history may not reveal its association with asbestos. Reference panels can be useful in assessing the former and analysis of lung tissue asbestos content may help to clarify the latter, especially in the low dose range. Electron microscopy may prove to be of assistance in this respect, possibly with particular attention to the peripheral areas of the lung. Animal experimentation has supported epidemiologic conclusions and revealed the phenomenon of fiber carcinogenesis. The morphology of mesothelioma in experimental animals is very similar to that in humans, including ultrastructural and biochemical features.}, } @article {pmid6993197, year = {1980}, author = {Lemen, RA and Dement, JM and Wagoner, JK}, title = {Epidemiology of asbestos-related diseases.}, journal = {Environmental health perspectives}, volume = {34}, number = {}, pages = {1-11}, pmid = {6993197}, issn = {0091-6765}, mesh = {Asbestos/*adverse effects/classification ; Asbestosis/epidemiology ; Environmental Exposure ; Humans ; Lung Neoplasms/epidemiology/etiology ; Mesothelioma/epidemiology/etiology ; Occupational Diseases/epidemiology/etiology ; Peritoneal Neoplasms/epidemiology/etiology ; Pleural Neoplasms/epidemiology/etiology ; Respiratory Tract Diseases/epidemiology/*etiology ; Smoking/complications ; }, abstract = {This paper is intended to give the reader an overview of the epidemiology of asbestos-related diseases and is restricted to primarily occupational exposure studies. However, some mention of nonoccupational exposures are made because of their direct relationship to a worker or to a secondary occupational source. Over 100 epidemiological studies are reviewed, dating back to the first case of asbestos-associated disease reported by Montague Murray in 1906. The studies are divided by specific fiber type and by specific disease outcomes and the interaction of asbestos and cigarette smoking is discussed in great detail.}, } @article {pmid7350360, year = {1980}, author = {Elliott, J}, title = {Experts cite paralysis of asbestos exposure control efforts.}, journal = {JAMA}, volume = {243}, number = {3}, pages = {211-3, 219}, doi = {10.1001/jama.243.3.211}, pmid = {7350360}, issn = {0098-7484}, mesh = {Asbestos/*adverse effects ; Asbestosis/*etiology ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/drug therapy/*etiology ; Peritoneal Neoplasms/etiology ; Pleural Neoplasms/etiology ; }, } @article {pmid7426112, year = {1980}, author = {Carton, B and Kauffer, E}, title = {The metrology of asbestos.}, journal = {Atmospheric environment}, volume = {14}, number = {10}, pages = {1181-1196}, doi = {10.1016/0004-6981(80)90183-3}, pmid = {7426112}, issn = {0004-6981}, mesh = {Air Pollutants/*analysis ; Air Pollutants, Occupational/*analysis ; Asbestos/*analysis/toxicity ; Digestive System Neoplasms/etiology ; Humans ; Lung Neoplasms/etiology ; Maximum Allowable Concentration ; Mesothelioma/etiology ; }, } @article {pmid7421277, year = {1980}, author = {Karakousis, CP and Seddiq, M and Moore, R}, title = {Malignant mesotheliomas and chemotherapy.}, journal = {Journal of surgical oncology}, volume = {15}, number = {2}, pages = {181-185}, doi = {10.1002/jso.2930150209}, pmid = {7421277}, issn = {0022-4790}, mesh = {Adult ; Aged ; Antineoplastic Agents/*administration & dosage ; Asbestos/adverse effects ; Cyclophosphamide/administration & dosage ; Dacarbazine/administration & dosage ; Doxorubicin/administration & dosage ; Drug Therapy, Combination ; Female ; Humans ; Male ; Mesothelioma/*drug therapy/etiology ; Middle Aged ; Peritoneal Neoplasms/*drug therapy/etiology ; Pleural Neoplasms/*drug therapy/etiology ; Prognosis ; Vincristine/administration & dosage ; }, abstract = {Of 77 patients with mesotheliomas, 63.6% had pleural involvement, 31.2% had peritoneal involvement, and 5.2% had involvement at other sites. The presenting symptoms varied with the location of the primary. Surgery and irradiation did not appear to influence the course of the diffuse type. Of 41 patients given systemic chemotherapy, three patients had complete response and four had greater than 50% objective response (median survival 42.5 months); 18 patients had stabilization (median 12.8 months), and 16 showed no response (median 4.5 months). The difference in survival between responders and non-responders was statistically significant (P < 0.001). Of 16 patients who received secondary chemotherapy, four had complete response (median survival 17.5 months), six had stabilization (median 10.5 months), and six had no response (median 2.5 months). Chemotherapy appears moderately effective in the treatment of mesotheliomas.}, } @article {pmid7414103, year = {1980}, author = {Epler, GR and Fitz Gerald, MX and Gaensler, EA and Carrington, CB}, title = {Asbestos-related disease from household exposure.}, journal = {Respiration; international review of thoracic diseases}, volume = {39}, number = {4}, pages = {229-240}, doi = {10.1159/000194221}, pmid = {7414103}, issn = {0025-7931}, support = {HL-07035/HL/NHLBI NIH HHS/United States ; HL-1173/HL/NHLBI NIH HHS/United States ; HL-19717/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; Asbestos/*adverse effects ; Asbestosis/*etiology/genetics ; Calcinosis/*etiology ; Environmental Exposure ; Female ; Humans ; Lung Neoplasms/*etiology ; Male ; Mesothelioma/*etiology ; Middle Aged ; Pleural Effusion/*etiology ; }, abstract = {The importance of nonoccupational asbestos exposure has been emphasized recently. To illustrate this problem, we report 4 persons with asbestos-related disease from household exposure. There were 2 wives of asbestos workers, who cleaned their husbands' work clothes. One developed a mesothelioma and the other plaques, calcification, benign asbestos pleural effusion and subpleural parenchymal fibrosis. 2 men were exposed as children while playing in a cellar room which was also used for their father's muffler repair business. At ages 27 and 33, they had pleural and diaphragmatic calcifications.}, } @article {pmid7392647, year = {1980}, author = {Edstrom, LE and Dawson, PJ and Kohler, J and DeMeester, TR}, title = {Malignant mesothelioma: a metastasis to the face.}, journal = {Journal of surgical oncology}, volume = {14}, number = {3}, pages = {251-254}, doi = {10.1002/jso.2930140310}, pmid = {7392647}, issn = {0022-4790}, mesh = {Facial Neoplasms/*secondary ; Humans ; Male ; Mesothelioma/mortality/pathology/*secondary/therapy ; Middle Aged ; Pleural Neoplasms/pathology ; }, abstract = {Malignant mesothelioma can be a confusing disease, resembling either carcinoma or sarcoma. Although it usually causes death rapidly by local and regional spread, distant metastases may be seen more frequently as more effective therapy controls local disease and prolongs life. Our patient's local and then regional mesothelioma was controlled by aggressive treatment, which allowed him nearly two years of productive life before a metastasis to the right infraorbital region occurred. He died shortly thereafter with widesspread metastases. This is the first reported case of mesothelioma metastatic to the face. This case also emphasizes the association of malignant mesothelioma with asbestos exposure, and points out advances in pathologic techniques that aid in the diagnosis of the disease.}, } @article {pmid7389191, year = {1980}, author = {Campbell, MJ and Wagner, MM and Scott, MP and Brown, DG}, title = {Sequential immunological studies in an asbestos-exposed population. II. Factors affecting lymphocyte function.}, journal = {Clinical and experimental immunology}, volume = {39}, number = {1}, pages = {176-182}, pmid = {7389191}, issn = {0009-9104}, mesh = {Aging ; Antibody-Dependent Cell Cytotoxicity ; Asbestos/*adverse effects ; DNA/biosynthesis ; Humans ; Lung Neoplasms/etiology/immunology ; Lymphocyte Activation ; Lymphocytes/*immunology ; Male ; Mesothelioma/etiology/immunology ; Middle Aged ; Occupational Diseases/immunology ; *Occupational Medicine ; Phytohemagglutinins ; Pokeweed Mitogens ; Pulmonary Fibrosis/etiology/immunology ; Smoking/complications ; }, abstract = {As part of an immunological study being carried out on a population exposed to asbestos the effect of two mitogens, phytohaemagglutinin (PHA) and pokeweed mitogen (PWM) on lymphocyte transformation has been assessed on three separate occasions for each mitogen. Both mitogens were assayed using foetal calf (FCS) or autologous serum (AS). Those men with pulmonary fibrosis (as measured by the presence of small opacities on X-ray) had a decrease (P less than 0.05) using PHA (FCS) when compared with those men with normal chest X-rays. Allowance has had to be made for the significant decline with age for both PHA (FCS and AS) transformation. There is a significant increase in PHA (FCS) and PWM (FCS) in ex-smokers and a further increase in smokers. These trends were consistent (at a lower level of significance) from survey to survey. There was no interaction between X-ray category and smoking. The lymphocyte antibody dependent cytotoxic test was measured on four occasions; the only observable effect was a non-significant increase in relation to smoking.}, } @article {pmid7375884, year = {1980}, author = {Vejlsted, H and Hansen, BF}, title = {Pleural mesothelioma.}, journal = {Scandinavian journal of thoracic and cardiovascular surgery}, volume = {14}, number = {1}, pages = {119-122}, doi = {10.3109/14017438009109866}, pmid = {7375884}, issn = {0036-5580}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; *Mesothelioma/diagnosis/pathology/therapy ; Middle Aged ; *Pleural Neoplasms/diagnosis/pathology/therapy ; }, abstract = {The difficulties in diagnosing pleural mesothelioma, both clinically and histopathologically, are documented by our experiences with this rare tumour during an 18-year-period. A rising incidence of pleural mesothelioma is reported in the literature, which is suspected to be caused by the increasing use of asbestos. This increase is not represented in a non-industrialized area. The heterogenous treatment reported in cases of malignant pleural mesothelioma illustrates the poor results achieved hitherto. Now treatment with either combination chemotherapy or radioactive drugs is recommended.}, } @article {pmid7239663, year = {1980}, author = {Gormley, IP and Wright, A and Collings, P and Davis, JM}, title = {The cytotoxicity of UICC and modified asbestos fibres in vitro.}, journal = {IARC scientific publications}, volume = {}, number = {30}, pages = {427-434}, pmid = {7239663}, issn = {0300-5038}, mesh = {Animals ; Asbestos/*pharmacology/standards ; Cell Line ; Cell Survival ; Erythrocytes/*pathology ; Hemolysis ; Macrophages/*pathology ; Microscopy, Electron ; *Particle Size ; Sheep ; }, abstract = {Samples of asbestos were tested for their potential to damage P388D1 cells and erythrocytes. The results obtained using the two systems were generally in agreement, with the amphibole being less cytotoxic and haemolytic than the chrysotile samples. Fibre length distributions for the chrysotile samples were relatively similar, so that, for this material, cytotoxicity and fibre length could not be correlated. However, some relationship was seen with amosite samples. Although there was agreement in some cases between cytotoxicity in vitro and the numbers of mesotheliomas produced in rats during a separate study using the same dusts, this relationship was not obvious for many of the samples tested.}, } @article {pmid7239661, year = {1980}, author = {Butler, EB and Johnson, NF}, title = {The use of electron microscopy in the diagnosis of diffuse mesotheliomas using human pleural effusions.}, journal = {IARC scientific publications}, volume = {}, number = {30}, pages = {409-418}, pmid = {7239661}, issn = {0300-5038}, mesh = {Adenocarcinoma/ultrastructure ; Animals ; Asbestos/*administration & dosage ; Carcinoma, Squamous Cell/ultrastructure ; Diagnosis, Differential ; Injections ; Mesothelioma/etiology/*ultrastructure ; Microscopy, Electron, Scanning ; *Pleural Effusion ; Pleural Neoplasms/etiology/*ultrastructure ; Rats ; }, abstract = {Transmission electron microscopy has been found to be of greater value than scanning electron microscopy in the differential diagnosis of mesothelial reaction, malignant mesothelioma and metastatic carcinoma. It is possible to remove identified cells from slides for transmission electron microscopy, and this is particularly valuable when an urgent diagnosis is required.}, } @article {pmid7239660, year = {1980}, author = {Beck, EG}, title = {Experimental pathology -- in vitro studies -- related to asbestos and other mineral fibres.}, journal = {IARC scientific publications}, volume = {}, number = {30}, pages = {385-400}, pmid = {7239660}, issn = {0300-5038}, mesh = {Animals ; Asbestos/*adverse effects ; Cell Division ; Cell Membrane Permeability ; Cell Survival ; Cells, Cultured ; Chlorocebus aethiops ; Cricetinae ; Erythrocyte Membrane/pathology ; Glass ; Guinea Pigs ; Hemolysis ; Macrophages/metabolism/*pathology/ultrastructure ; Mice ; Particle Size ; Rats ; }, abstract = {Current studies on the biologically relevant characteristics of inhalable fibres are described, including the papers presented in this session. The various cell systems used in in vitro tests, i.e., diploid and permanent proliferating and nonproliferating cells, are listed, as are the different endpoints of these tests. It is shown that use of in vitro tests complements the use of animal experimentation. Opinions on the nature of the acute toxic effects of asbestos fibres on macrophages differ; however, the dependence of toxicity on fibre length has been demonstrated in this system. These data show that the effects of mineral fibres in vitro give an indication of their potential fibrogenicity in vivo. Other cell culture systems, reported in papers in this session, include hamster lung fibroblasts, rat pleural mesothelial cells and mesothelioma cells. Experiments in which fibre geometry is altered, e.g., by acid treatment, indicate that it is an important factor in cytotoxicity; the haemolytic effect of fibres, however, appears to depend on their chemical composition. Thus, a combined physical-chemical effect would appear to be involved. In vitro testing has also made possible investigation of immunological and chromosomal changes due to inhalation of asbestos fibres. The practical use of findings made in vitro is also summarized.}, } @article {pmid7239658, year = {1980}, author = {Wagner, JC and Berry, G and Skidmore, JW and Pooley, FD}, title = {The comparative effects of three chrysotiles by injection and inhalation in rats.}, journal = {IARC scientific publications}, volume = {}, number = {30}, pages = {363-372}, pmid = {7239658}, issn = {0300-5038}, mesh = {Animals ; Asbestos/*administration & dosage ; Female ; Inhalation ; Injections ; Lung Neoplasms/etiology ; Male ; Mesothelioma/*etiology ; Particle Size ; Pleural Neoplasms/*etiology ; Pulmonary Fibrosis/etiology ; Rats ; Talc/administration & dosage ; Time Factors ; }, abstract = {Three samples of chrysotile, UICC Canadian chrysotile, a grade 7 Canadian chrysotile and a super fine sample (SFA) also from a Canadian mine, were compared in animal experiments using rats of the Wistar strain. All the materials contained impurities. The average length and diameter of the fibres contained in the UICC chrysotile cloud were less than for the other two chrysotiles, but the higher fibre count meant that the UICC cloud contained more fibres of all lengths. In the first experiment, groups of 48 rats were injected intrapleurally with 20 mg of respirable dust. Mesotheliomas occurred with all samples; 18 with SFA, 13 with grade 7, and five with UICC chrysotile. In the second experiment, rats were exposed to a respirable cloud of about 1 mg/m3 for 35 hours a week. Groups of 48 rats were exposed for three months, 24 for six months and 24 for 12 months. Malignant lung tumours occurred with all the dusts; 10 with UICC chrysotile, 4 with SFA, and 1 with grade 7. However, only one of these tumours, obtained with SFA, was a mesothelioma.}, } @article {pmid7239656, year = {1980}, author = {Smith, WE and Hubert, DD and Sobel, HJ}, title = {Dimensions of fibres in relation to biological activity.}, journal = {IARC scientific publications}, volume = {}, number = {30}, pages = {357-360}, pmid = {7239656}, issn = {0300-5038}, mesh = {Animals ; Asbestos/*administration & dosage/adverse effects/standards ; Cricetinae ; Diet ; Evaluation Studies as Topic ; Female ; *Glass ; Inhalation ; Injections ; Male ; Mesocricetus ; *Particle Size ; Thoracic Neoplasms/*etiology ; Time Factors ; }, abstract = {Intrathoracic tumours were induced in Syrian golden hamsters given intrapleural injections of chrysotile, tremolite or glass fibres; but the carcinogenicity of these materials was reduced or disappeared with reductions in fibre size. After lifetime administration of UICC amosite in drinking-water, a peritoneal mesothelioma, a pulmonary carcinoma and two early squamous-cell carcinomas of the forestomach were found in 4 of 180 hamsters. No tumours related to treatment were found in animals exposed to fibre-shaped particles of cummingtonite/grunerite, mineralogically related to amosite but of shorter length.}, } @article {pmid7239655, year = {1980}, author = {Bossard, E and Stolkin, I and Spycher, MA and Ruttner, JR}, title = {Quantification and particle size distribution of inhaled fibres in the lung.}, journal = {IARC scientific publications}, volume = {}, number = {30}, pages = {35-41}, pmid = {7239655}, issn = {0300-5038}, mesh = {Adult ; Aged ; Air Pollutants, Occupational ; Asbestos/*adverse effects/analysis ; Asbestosis/etiology/pathology ; Female ; Humans ; Inhalation ; Lung/analysis/*pathology ; Male ; Mesothelioma/etiology/pathology ; Middle Aged ; *Particle Size ; Silicosis/etiology/pathology ; }, abstract = {The number and size distribution of fibres in the lungs of 11 asbestos-exposed and 10 nonexposed individuals were determined. For fibre isolation, low-temperature incineration of lung tissue was used. The mean numbers of fibres per gram of dry lung, based on light microscopy, were 141.9 X 10(6) and 1.5 X 10(6) in the asbestos-exposed and nonexposed lungs, respectively. The fibre length found most frequently ranged between 3-5 micrometers in both groups. Asbestos, either chrysotile or amphibole, was found only in the group occupationally exposed to asbestos. No correlation between number of fibres and lung pathology could be established.}, } @article {pmid7239654, year = {1980}, author = {Pylev, LN}, title = {Pretumorous lesions and lung and pleural tumours induced by asbestos in rats, Syrian golden hamsters and Macaca mulatta (rhesus) monkeys.}, journal = {IARC scientific publications}, volume = {}, number = {30}, pages = {343-355}, pmid = {7239654}, issn = {0300-5038}, mesh = {Adenocarcinoma/etiology/pathology ; Animals ; Asbestos/*administration & dosage ; Cricetinae ; Hyperplasia ; Injections ; Lung Neoplasms/*etiology/pathology ; Macaca mulatta ; Mesocricetus ; Mesothelioma/etiology/pathology ; Pleural Neoplasms/*etiology/pathology ; Precancerous Conditions/*etiology/pathology ; Rats ; }, abstract = {Asbestos samples were injected into the right pleural cavity of random-bred rats (20 mg thrice monthly). Milled commercial chrysotile induced pleural mesotheliomas in 65.5%, its dust in 46.3%, milled synthetic chrysotile in 2.4%, milled commercial magnesia-arphvedsonite in 77.1%, milled commercial anthophyllite in 41.4%, its dust in 64.9% and milled synthetic hydroxyamphibole in 54.5%. Intratracheal injections (10 mg twice monthly) of milled commercial chrysotile into Syrian golden hamsters induced lung tumours in 63% (malignant in 44.4%, benign in 18.5%), synthetic chrysotile in 23% (malignant in 7.7%, benign in 15.3%), commercial magnesia-arphvedsonite (5 mg twice monthly) in 80.8% (malignant in 46.2%, benign in 34.6%) and synthetic hydroxyamphibole (5 mg twice monthly) in 63.4% (malignant in 19.2%, benign in 44.2%). Benzo[a]pyrene adsorbed or added to asbestos dust stimulated asbestos-induced lung carcinogenesis in rats but had no influence on pleural carcinogenesis. Pretumorous lesions were found in lung tissue and in pleural mesothelium in all experiments in rats, hamsters and monkeys after instillations of asbestos into the lungs and pleural cavity. The morphological picture of the pretumorous lesions and tumours was similar in all experiments. Diffuse and focal hyperplasia and proliferation of epithelium-like and fibroblast-like mesothelial cells were observed. Benign (adenoma-like, fibrous) and malignant (carcinoma-like, sarcoma-like, mixed) mesotheliomas were also found.}, } @article {pmid7239653, year = {1980}, author = {Pott, F and Huth, F and Spurny, K}, title = {Tumour induction after intraperitoneal injection of fibrous dusts.}, journal = {IARC scientific publications}, volume = {}, number = {30}, pages = {337-342}, pmid = {7239653}, issn = {0300-5038}, mesh = {Abdominal Neoplasms/*etiology/pathology ; Age Factors ; Animals ; Asbestos/administration & dosage/analysis/metabolism ; Asbestosis/complications ; Cricetinae ; Diaphragm/analysis ; Dust ; Female ; *Glass/analysis ; Injections ; Mesothelioma/*etiology/pathology ; Rabbits ; Rats ; Spleen/analysis ; }, abstract = {I.p. injection of glass fibres to rats of different strains resulted partly in different tumour rates. Young rats showed more marked coalescence and earlier growth of tumours but also earlier mortality without tumours, as compared with older rats. Haemorrhagic ascites from tumour-bearing rats induced tumours after i.p. injection. Tumours were also obtained after i.p. injection of fibres in European hamsters and rabbits, but these species are less susceptible than rats. Histological studies in rats show that fibrosis is not an absolute requirement for the development of a fibre-induced mesothelioma. After intratracheal instillation of either crocidolite or glass fibres in European hamsters, the respective fibres showed up in the diaphragm and in the spleen.}, } @article {pmid7239650, year = {1980}, author = {Lafuma, J and Morin, M and Poncy, JL and Masse, R and Hirsch, A and Bignon, J and Monchaux, G}, title = {Mesothelioma induced by intrapleural injection of different types of fibres in rats; synergistic effect of other carcinogens.}, journal = {IARC scientific publications}, volume = {}, number = {30}, pages = {311-320}, pmid = {7239650}, issn = {0300-5038}, mesh = {Animals ; Asbestos/administration & dosage/*adverse effects ; Glass ; Injections ; Lung Neoplasms/etiology ; Mesothelioma/*etiology ; Neutrons ; Pleural Neoplasms/*etiology ; Radon/adverse effects ; Rats ; Time Factors ; }, abstract = {Intrapleural injections of 20 mg of various mineral fibres were made to rats. Three types of fibres (chrysotile, crocidolite and glass fibres) were untreated; other chrysotile fibres were leached to different degrees. The results show that chrysotile is the most toxic of the three: animals died sooner and presented mesotheliomas earlier. With increased leaching, toxicity and carcinogenic effect decreased. Crocidolite is less toxic than untreated chrysotile but later produces as many mesotheliomas; with glass fibres, some mesotheliomas are observed. Small groups of animals were exposed to two types of irradiation before intrapleural injection of 2 mg of chrysotile. Whole-body irradiation was delivered to a third group of animals which were given asbestos-contaminated food. The paper analyses the synergistic action of these two insults.}, } @article {pmid7239644, year = {1980}, author = {Wassermann, M and Wassermann, D and Steinitz, R and Katz, L and Lemesch, C}, title = {Mesothelioma in children.}, journal = {IARC scientific publications}, volume = {}, number = {30}, pages = {253-257}, pmid = {7239644}, issn = {0300-5038}, mesh = {Adolescent ; Animals ; Asbestos/administration & dosage/*adverse effects ; Child ; Child, Preschool ; Dust ; Environmental Exposure ; Female ; Fetus ; Humans ; Injections, Intravenous ; Male ; Mesothelioma/epidemiology/*etiology ; Peritoneal Neoplasms/epidemiology/*etiology ; Pleural Neoplasms/epidemiology/*etiology ; Pregnancy ; Sheep ; Time Factors ; }, abstract = {A literature review of mesothelioma in children is presented. The role of nonoccupational exposure to asbestos fibres in the etiology of mesothelioma, and the relatively short latent period of the disease in children are discussed. The transplacental transfer of asbestos fibres and the physiology of the immunological system during intrauterine life and infancy may explain some of the differences between mesotheliomas in children and those in adults.}, } @article {pmid7239643, year = {1980}, author = {Wagner, MM}, title = {Immunology and asbestos.}, journal = {IARC scientific publications}, volume = {}, number = {30}, pages = {247-251}, pmid = {7239643}, issn = {0300-5038}, mesh = {Asbestos/adverse effects/*immunology ; Humans ; Leukocyte Count ; Longitudinal Studies ; Lymphocytes/immunology ; Male ; Monocytes/immunology ; Occupational Diseases/diagnostic imaging/etiology/*immunology ; Pulmonary Fibrosis/diagnostic imaging/etiology/*immunology ; Radiography ; Rosette Formation ; }, abstract = {A population exposed to asbestos while working in a dockyard has been studied longitudinally. Immunological tests using markers for subsets of lymphocytes and monocytes were employed. Evidence is presented that suggests that those with progressing pulmonary fibrosis may be pinpointed. From animal experimental work in relation to mesothelioma, it is suggested that macrophages may play a role in the control of this tumour.}, } @article {pmid7239642, year = {1980}, author = {Sebastien, P and Janson, X and Gaudichet, A and Hirsch, A and Bignon, J}, title = {Asbestos retention in human respiratory tissues: comparative measurements in lung parenchyma and in parietal pleura.}, journal = {IARC scientific publications}, volume = {}, number = {30}, pages = {237-246}, pmid = {7239642}, issn = {0300-5038}, mesh = {Adult ; Aged ; Air Pollutants, Occupational ; Asbestos/*analysis ; Environmental Exposure ; Female ; Humans ; Lung/*analysis/pathology ; Lung Neoplasms/pathology ; Male ; Mesothelioma/pathology ; Microscopy, Electron, Scanning ; Middle Aged ; Particle Size ; Pleura/*analysis/pathology ; Pleural Effusion/pathology ; Pulmonary Fibrosis/pathology ; }, abstract = {Asbestos fibres in respiratory tissues from 29 cases diversely exposed to asbestos dusts have been characterized, sized and counted using a transmission electron microscope. Comparison of data obtained by measurement of fibres in lung parenchyma and in parietal pleura samples showed the following: -- In each case, the proportion of chrysotile fibres (as opposed to amphiboles) was higher in parietal pleura than in lung parenchyma. (The proportion of chrysotile in pleura was greater than 90% in 30 of the 40 samples.) -- Fibres encountered in parietal pleura were shorter than those in the parenchyma. -- There was no evident correlation between numerical concentrations of fibres in lung parenchyma and those in parietal pleura. This study has shown that characteristics of asbestos retention in parietal pleura cannot be derived from measurements in lung parenchyma. On the basis of the cases analysed here, who were exposed to mixed types of asbestos dust, chrysotile seems to be the asbestos type retained almost exclusively in parietal pleural tissues. These findings might be taken into account when assessing the risk of pleural diseases (especially mesothelioma) attributable to each type of asbestos fibre.}, } @article {pmid7239638, year = {1980}, author = {Lopez-Areal Del Amo, L}, title = {Diseases associated with asbestos in Spain.}, journal = {IARC scientific publications}, volume = {}, number = {30}, pages = {201-206}, pmid = {7239638}, issn = {0300-5038}, mesh = {Adult ; Asbestos/*adverse effects ; Asbestosis/*epidemiology/etiology ; Bronchial Neoplasms/epidemiology/etiology ; Environmental Exposure ; Humans ; Middle Aged ; Pleura/pathology ; Spain ; Textile Industry ; }, abstract = {In Spain, imported asbestos of all types is processed into fibre-cement and textile and friction materials, involving about 9000 workers. The author describes his studies in a small textile firm in Bilbao manufacturing textile and cardboard asbestos products from chrysotile and, until 1970, crocidolite. No mesotheliomas were found, but asbestosis, bronchial cancer and pleural changes were seen. Other studies carried out in Spain are described also.}, } @article {pmid7239637, year = {1980}, author = {Jones, JS and Pooley, FD and Clark, NJ and Owen, WG and Roberts, GH and Smith, PG and Wagner, JC and Berry, G and Pollock, DJ}, title = {The pathology and mineral content of lungs in cases of mesothelioma in the United Kingdom in 1976.}, journal = {IARC scientific publications}, volume = {}, number = {30}, pages = {187-199}, pmid = {7239637}, issn = {0300-5038}, mesh = {Adult ; Aged ; Air Pollutants, Occupational ; Asbestos/*adverse effects/analysis/classification ; Dust ; Female ; Health Surveys ; Humans ; Lung/analysis/*pathology ; Male ; Mesothelioma/*epidemiology/etiology/pathology ; Middle Aged ; Peritoneal Neoplasms/epidemiology/pathology ; Pleural Neoplasms/epidemiology/pathology ; Probability ; United Kingdom ; }, abstract = {A study was made of 93 cases of mesothelioma who died in 1976 in the United Kingdom. Lung tissue was available for mineral fibre analysis from 86 of these cases, and also from 29 cases of cerebrovascular disease and 27 cases of bronchial carcinoma, matched for place of death, age and sex with the mesothelioma cases. It was observed that: (1) mesothelioma patients had more amphibole fibres in their lungs than did control cases; (2) chrysotile fibres were not present in greater numbers in the mesothelioma patients than in the control cases; (3) four of the mesothelioma cases had no amphibole fibres in their lungs; two of these had chrysotile fibres, and the other two had no asbestos fibres; and (4) 30 cases of mesothelioma had no chrysotile fibres in their lungs.}, } @article {pmid7239636, year = {1980}, author = {Bignon, J and Sebastien, P and Gaudichet, A and Jaurand, MC}, title = {Biological effects of attapulgite.}, journal = {IARC scientific publications}, volume = {}, number = {30}, pages = {163-181}, pmid = {7239636}, issn = {0300-5038}, mesh = {Adult ; Air Pollutants, Occupational ; Animals ; Drug Contamination ; Female ; France ; Humans ; Inhalation ; Injections, Intraperitoneal ; Mesothelioma/etiology ; Microscopy, Electron, Scanning ; Minerals/administration & dosage/*adverse effects/analysis ; Particle Size ; Rats ; Spain ; }, abstract = {Some clay minerals occur naturally in a fibrous or lath-like crystal state as attapulgite and sepiolite. Because of their sorptive and colloidal properties, attapulgite and sepiolite have numerous industrial applications, mainly as additives in oil-drilling muds, in chemical fertilizers, pesticides, paints, adhesive products, bleaching agents, cosmetic compounds and phytosanitary products. World consumption of each is over one million tons annually. Acid-treated attapulgite is used in the composition of certain drugs used for the treatment of gastrointestinal diseases. Such drugs available commercially in France were analysed for their mineral content by transmission electron microscopy and found to contain attapulgite fibres [mean length: 0.9 micrometers (0.1-3.6); mean diameter: 0.05 micrometers (0.01-0.5)]. The haemolytic activities of a Spanish attapulgite sample and of three samples of drugs sold in France were greater or similar to that of UICC chrysotile asbestos. Attapulgite fibres were encountered in large quantities in the lung washing fluid of a patient suffering from lung fibrosis who had been exposed recently for three years during the processing of attapulgite material. Attapulgite fibres were also found in a urine sample from a patient who had ingested 6-9 g/day of an attapulgite drug for six months.}, } @article {pmid7228346, year = {1980}, author = {Baris, Y}, title = {The clinical and radiological aspects of 185 cases of malignant pleural mesothelioma.}, journal = {IARC scientific publications}, volume = {}, number = {30}, pages = {937-947}, pmid = {7228346}, issn = {0300-5038}, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Asbestos ; Environmental Exposure ; Female ; Humans ; Male ; Mesothelioma/diagnostic imaging/*epidemiology/etiology ; Middle Aged ; Pleural Neoplasms/diagnostic imaging/*epidemiology/etiology ; Radiography ; Sex Factors ; Smoking ; Socioeconomic Factors ; Turkey ; }, abstract = {One hundred and eight-five cases of environmentally-caused malignant pleural mesothelioma were analysed for clinical and radiological pictures. The first group consisted of 122 subjects from villages with asbestos deposits. The second group consisted of 63 patients from the Cappadocia region where there are no asbestos deposits but where zeolite occurs. The mean age at death and the age range of the patients were lower than those of patients with occupationally-caused mesothelioma. This can be explained by the fact that exposure to mineral fibres in Turkey begins immediately after birth. The mode of onset was insidious chest pain, and the mean interval before reaching hospital was six months. The average duration of illness from the onset of symptoms to death was nearly 18 months. The most common clinical findings were evidence of pleural effusion and thickening. Bronchial breathing, tumour extension to the chest wall and frozen chest were also observed. Horner's syndrome was recorded in seven cases, and hypoglycaemia features in two. Pleural effusions and thickening, nodular and lobular lesions in the pleura, calcified pleural plaques with pleural lesions and hydropneumothorax were the radiological manifestations of malignant pleural mesothelioma. Three patients with mesothelioma were being followed up after a diagnosis of asbestos-caused pleurisy.}, } @article {pmid7228341, year = {1980}, author = {Leineweber, JP}, title = {Dust chemistry and physics: mineral and vitreous fibres.}, journal = {IARC scientific publications}, volume = {}, number = {30}, pages = {881-900}, pmid = {7228341}, issn = {0300-5038}, mesh = {Biological Availability ; Chemical Phenomena ; Chemistry ; *Dust ; *Glass ; Humans ; Mesothelioma/etiology ; Microscopy, Electron, Scanning ; *Minerals ; Occupational Diseases/etiology ; Particle Size ; Physical Phenomena ; Physics ; }, abstract = {Increasing attention is currently being addressed to the many aspects of biological effects of fibres other than asbestos. In part, this interest has been generated by the work of Drs Stanton, Pott and others. The demonstration that durable fibres, of almost any composition, which satisfy certain dimensional requirements can induce tumours when implanted into the pleural or peritoneal cavities of mammals has generated concern over effects analogous to those of asbestos in man. Recent data from Turkey have suggested that fibrous zeolites can also produce mesothelioma in man. The chemical and physical properties of relevant, naturally occurring, as well as man-made mineral fibres are discussed. Particular emphasis is laid on those properties that are believed to be significant determinants of biological activity.}, } @article {pmid7228339, year = {1980}, author = {Peto, J}, title = {Lung cancer mortality in relation to measured dust levels in an asbestos textile factory.}, journal = {IARC scientific publications}, volume = {}, number = {30}, pages = {829-836}, pmid = {7228339}, issn = {0300-5038}, mesh = {Aged ; Asbestos/*analysis ; Dust/*analysis ; Follow-Up Studies ; Humans ; Lung Diseases/mortality ; Lung Neoplasms/etiology/*mortality ; Male ; Mesothelioma/mortality ; Middle Aged ; Occupational Diseases/etiology/mortality ; Textile Industry ; Time Factors ; United Kingdom ; }, abstract = {A cohort of 255 men who entered this factory since the beginning of 1951, when routine dust sampling weas initiated, have been followed up to the end of 1978. Eight (1.62 expected) died of lung cancer over 20 years after first exposure (P less than 0.001). Earlier estimates of dust levels hve been revised to correspond to modern counting methods, and the average cumulative exposure of this cohort is now estimated to have been 200-300 fibres/ml-years. No deaths have yet been attributed to asbestosis, but a separate study of this group has reported that 10 of these men have been certified as asbestotic. An earlier analysis of lung cancer, mesothelioma and asbestosis incidence in men employed prior to 1951 suggested a dose-response relationship for lung cancer in relation to static sampler dust measurements that was probably approximately correct, but it is not clear whether personal sampling wound give similar results.}, } @article {pmid7228337, year = {1980}, author = {Mikheev, MI}, title = {Biological effects of asbestos in relation to control of occupational exposure.}, journal = {IARC scientific publications}, volume = {}, number = {30}, pages = {819-821}, pmid = {7228337}, issn = {0300-5038}, mesh = {Asbestos/adverse effects/*toxicity ; Humans ; Maximum Allowable Concentration ; Mesothelioma/etiology/*prevention & control ; Occupational Diseases/prevention & control ; }, abstract = {The health risks of asbestos exposure and the adequacy of measures to limit the biological effects of exposure are discussed. The toxicological properties of asbestos are considered, and it is postulated that a nonthreshold approach could be used to establish an appropriate permissible level of occupational exposure to the substance.}, } @article {pmid7228334, year = {1980}, author = {Hunter, WJ and Recht, P}, title = {Scientific aspects of the work of the Commission of the European Communities on Asbestos.}, journal = {IARC scientific publications}, volume = {}, number = {30}, pages = {775-782}, pmid = {7228334}, issn = {0300-5038}, mesh = {Air Pollutants, Occupational/analysis ; Asbestos/*adverse effects/analysis ; Asbestosis/etiology/*prevention & control ; Europe ; Humans ; Lung/analysis ; Mesothelioma/etiology/*prevention & control ; Organizations/standards ; }, abstract = {The Commission of the European Communities has been carrying out scientific investigations on asbestos for some years. The principal activity has been the regular meetings of two European Communities panels of scientific consultants concerned primarily with the pathology of the asbestos-related diseases, asbestosis and mesothelioma. In addition, the Commission has carried out a number of comparative studies on the measurement of asbestos in various media, using both gravimetric and microscopic techniques.}, } @article {pmid7228329, year = {1980}, author = {Talent, JM and Harrison, WO and Solomon, A and Webster, I}, title = {A survey of black mineworkers of the Cape crocidolite mines.}, journal = {IARC scientific publications}, volume = {}, number = {30}, pages = {723-729}, pmid = {7228329}, issn = {0300-5038}, mesh = {*Black or African American ; *Asbestos ; Asbestosis/*epidemiology/etiology ; Black People ; Follow-Up Studies ; Humans ; Mesothelioma/*epidemiology/etiology ; Mining ; Pleural Neoplasms/*epidemiology/etiology ; South Africa ; Time Factors ; }, abstract = {Between 1974-1978, a study group 970 mineworkers exposed from before July 1962 only to Cape crocidolite were traced: 755 were alive and 215 dead. Of those still alive, 66.1% showed no radiological abnormalities of the chest; 8.9% had irregular small opacities only; 17.7% had pleural abnormalities only; and 7.3% had both. Five pleural mesotheliomas were found in living ex-workers; although only one was reported in those who had died, this was considered to be an underestimate. The incidences of pleural mesotheliomas in ex-employees of the mining industry outside of the study group are also described.}, } @article {pmid7228328, year = {1980}, author = {Rossiter, CE and Coles, RM}, title = {HM Dockyard, Devonport: 1947 mortality study.}, journal = {IARC scientific publications}, volume = {}, number = {30}, pages = {713-721}, pmid = {7228328}, issn = {0300-5038}, mesh = {Aged ; *Asbestos ; Asbestosis/etiology/*mortality ; Follow-Up Studies ; Humans ; Life Expectancy ; Male ; Mesothelioma/etiology/*mortality ; Middle Aged ; Occupational Diseases/etiology/mortality ; Pulmonary Fibrosis/etiology/*mortality ; Ships ; Wales ; }, abstract = {To investigate the effect of occupational exposure to asbestos on mortality, names of all 6292 men born on or after 1 January 1910 and employed as industrial workers in the RN Dockyard, Devonport on 1 January 1947 were submitted to the Office of Population Censuses and Surveys for tracing. Follow-up continued until the end of 1978: over 99% were traced; 3% emigrated; and there were 1043 (17%) deaths. On the basis of the mortality in England and Wales for each five years of age and each five calendar years, the standardized mortality ratio (SMR) was 96. Adjusting the rates for the lower mortality in south-west England, the SMR was 104. No relation was found between SMR and date of birth, and there was only a very slight excess among those more heavily exposed to asbestos. Thirty-one men died with mesothelioma and a further 14 with asbestosis or pulmonary fibrosis. The circulatory disease death rate was slightly raised (SMR = 118), but no more than might have been expected for manual workers. Asbestos-related deaths accounted for at least 4% of all deaths, but probably not many more.}, } @article {pmid7228327, year = {1980}, author = {Peto, J}, title = {The incidence of pleural mesothelioma in chrysotile asbestos textile workers.}, journal = {IARC scientific publications}, volume = {}, number = {30}, pages = {703-711}, pmid = {7228327}, issn = {0300-5038}, mesh = {Adult ; Age Factors ; Aged ; *Asbestos ; England ; Female ; Humans ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Diseases/epidemiology/etiology ; Pleural Neoplasms/*epidemiology/etiology ; Risk ; Textile Industry ; Time Factors ; }, abstract = {Analysis of the incidence of pleural mesothelioma in asbestos textile workers in relation to age, time since first exposure, intensity of exposure and period of observation indicates that age per se is largely irrelevant; that is, the incidence 30 years after first exposure appears to be much the same irrespective of age at first exposure. This has been shown to be true in animal experiments and has been suggested on theoretical grounds for certain human cancers; it explains the evolution of lung cancer rates in relation to changing smoking habits but has not been demonstrated directly by human data. These results also suggest that mesothelioma incidence may not have been much underestimated in the past, which would imply that the recent marked increase in recorded rates is largely real and not merely a diagnostic artefact. The risk does not appear to have been much higher among men who were initially very heavily exposed. One possible explanation of this surprising observation is that chrysotile is eliminated, or ceases to be biologically active, more quickly than other types of asbestos.}, } @article {pmid7228326, year = {1980}, author = {Perdrizet, S and Bignon, J and Di Menza, L and Nebut, M}, title = {French mesothelioma register: critical appraisal of the registered data.}, journal = {IARC scientific publications}, volume = {}, number = {30}, pages = {697-701}, pmid = {7228326}, issn = {0300-5038}, mesh = {Asbestos/*adverse effects ; Evaluation Studies as Topic ; France ; Humans ; Mesothelioma/epidemiology/*etiology ; *Registries/standards ; }, abstract = {The French mesothelioma register has three objectives. The first, collection of morbidity data could not be achieved since the data collected are not exhaustive. The second, the collection of histological material for establishing diagnostic criteria, has provided interesting data; and the third, etiological research, may constitute the basis for well-defined studies.}, } @article {pmid7228324, year = {1980}, author = {McDonald, AD}, title = {Mineral fibre content of lung in mesothelial tumours: preliminary report.}, journal = {IARC scientific publications}, volume = {}, number = {30}, pages = {681-685}, pmid = {7228324}, issn = {0300-5038}, mesh = {Asbestos/*adverse effects/analysis ; Female ; Humans ; Lung/analysis ; Lung Neoplasms/etiology/*mortality/secondary ; Male ; Mesothelioma/etiology/*mortality ; North America ; Occupational Diseases/etiology/mortality ; }, abstract = {A survey was made, through pathologists, of all 274 fatal cases of primary malignant mesothelioma in North America in 1972. For each case, a control with pulmonary metastases from a primary tumour other than lung cancer was matched for sex and age. Relatives and friends of both cases and controls were interviewed; and specimens of lung tissue were obtained for 100 case-control pairs and analysed 'blind' by electron microscopy and X-ray energy dispersion analysis. This report describes the preliminary results of the analyses of asbestos fibres in the first 37 case-control pairs: chrysotile fibres were far more prevalent than amphiboles, but equal quantities were found in cases and controls. There was, however, a clear excess of amosite fibres in male cases as compared with controls.}, } @article {pmid7228323, year = {1980}, author = {McDonald, AD}, title = {Malignant mesothelioma in Quebec.}, journal = {IARC scientific publications}, volume = {}, number = {30}, pages = {673-680}, pmid = {7228323}, issn = {0300-5038}, mesh = {*Asbestos ; Female ; Humans ; Male ; Mesothelioma/etiology/*mortality ; Mining ; Occupational Diseases/etiology/mortality ; Peritoneal Neoplasms/etiology/mortality ; Pleural Neoplasms/etiology/mortality ; Quebec ; Risk ; }, abstract = {All known, fatal cases of mesothelioma in the period 1960-1978 in the Province of Quebec are reviewed, because much of the world's chrysotile has been produced there and because there is also exposure to other types of asbestos. Of the 254 mesotheliomas registered, 181 were in males and 73 in females; occupational and residential histories were obtained for 91% of men and 86% of women. About 40% of male cases were probably attributable to occupational asbestos exposure; only 5.4% of females cases had been exposed occupationally. Intervals between first employment and death from mesothelioma were longer for miners and millers than for manufacturing workers: exposures of chrysotile miners and millers were mainly long and fairly low, while many factory workers had had short exposures. All tumours in miners and millers were pleural, while in factory workers, eight were peritoneal and two pleural and peritoneal. The evidence from this survey supports the view that the risk of mesothelioma after exposure to crocidolite is many times greater than that after chrysotile.}, } @article {pmid7228322, year = {1980}, author = {Liddell, FD}, title = {Validation of the UICC/Cincinnati classification of radiographs in terms of prediction of mortality of asbestos workers.}, journal = {IARC scientific publications}, volume = {}, number = {30}, pages = {667-671}, pmid = {7228322}, issn = {0300-5038}, mesh = {Asbestos ; Asbestosis/*diagnostic imaging/mortality ; Humans ; Lung Neoplasms/*diagnostic imaging/mortality ; Male ; Mesothelioma/*diagnostic imaging/mortality ; Middle Aged ; Occupational Diseases/diagnostic imaging/mortality ; Prognosis ; Quebec ; Radiography ; Technology, Radiologic ; }, abstract = {The mortality of 4559 Quebec chrysotile workers has been related to the findings from their last routine chest X-ray while still employed. In those 84 lung cancer cases who were X-rayed less than 10 years before their death, over two-thirds had 'less-than-normal' films; the abnormality was not specific, except for 'large opacities'. The three men who died from mesothelioma within about a year of X-ray were 'less-than-normal'. The findings of the completed project validated convincingly the 1967 UICC/Cincinnati classification.}, } @article {pmid7228320, year = {1980}, author = {Lewinsohn, HC and Meigs, JW and Teta, MJ and Flannery, JT}, title = {The influence of occupational and environmental asbestos exposure on the incidence of malignant mesothelioma in Connecticut.}, journal = {IARC scientific publications}, volume = {}, number = {30}, pages = {655-660}, pmid = {7228320}, issn = {0300-5038}, support = {N01 CP 33235/CP/NCI NIH HHS/United States ; N01 CP 61002/CP/NCI NIH HHS/United States ; }, mesh = {Age Factors ; Asbestos/*adverse effects ; Connecticut ; Environmental Exposure ; Female ; Humans ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Diseases/epidemiology/etiology ; Pleural Neoplasms/*epidemiology/etiology ; Registries ; Sex Factors ; Time Factors ; }, abstract = {Medical, occupational and demographic data were collected for 229 cases of malignant mesothelioma and 38 other pleural tumours, their spouses, and 605 controls. Methods were developed for classifying subjects into probable asbestos exposure categories. Although disease incidence rates exhibited a rapid increase from 1955 to 1977, there remains a serious question of diagnostic reliability. A case review is being undertaken.}, } @article {pmid7228319, year = {1980}, author = {Jones, JS and Smith, PG and Pooley, FD and Berry, G and Sawle, GW and Madeley, RJ and Wignall, BK and Aggarwal, A}, title = {The consequences of exposure to asbestos dust in a wartime gas-mask factory.}, journal = {IARC scientific publications}, volume = {}, number = {30}, pages = {637-653}, pmid = {7228319}, issn = {0300-5038}, mesh = {Asbestos/*adverse effects/analysis ; Bronchial Neoplasms/epidemiology ; England ; Female ; Humans ; Lung/analysis ; Male ; Mesothelioma/etiology/*mortality ; Middle Aged ; Occupational Diseases/mortality ; Peritoneal Neoplasms/mortality ; Pleural Neoplasms/mortality ; Time Factors ; }, abstract = {This further study of wartime gas-mask workers who were exposed to asbestos dust has shown that among those who worked with crocidolite there is a considerable excess of cases of mesothelioma, a more modest excess of bronchial carcinoma, but no excess of any other type of malignant disease. A dose-response relationship is established in the mesothelioma and bronchial carcinoma patients. It is not possible to base any conclusions on the limited data available for the small number of people exposed to chrysotile for a maximum period of five months. We believe that the identification and measurement of fibres in autoptic lung tissue from patients with accurately known occupational histories of asbestos dust exposure is useful, and a similar study on a population exclusively exposed to chrysotile would be of considerable interest.}, } @article {pmid7228317, year = {1980}, author = {Hobbs, MS and Woodward, SD and Murphy, B and Musk, AW and Elder, JE}, title = {The incidence of pneumoconiosis, mesothelioma and other respiratory cancer in men engaged in mining and milling crocidolite in Western Australia.}, journal = {IARC scientific publications}, volume = {}, number = {30}, pages = {615-625}, pmid = {7228317}, issn = {0300-5038}, mesh = {Asbestos ; Asbestosis/*epidemiology/mortality ; Australia ; Humans ; Male ; Mesothelioma/*epidemiology/etiology/mortality ; Mining ; Occupational Diseases/epidemiology/mortality ; Respiratory Tract Neoplasms/*epidemiology/etiology/mortality ; Time Factors ; }, abstract = {Previous employees of a mining company, engaged in mining of crocidolite at Wittenoom Gorge in Western Australia between 1943 and 1966, have been traced to determine their incidence of asbestos-related diseases. Of 6200 male employees, 220 (3.5%) have developed pneumoconiosis and 26 have developed pleural mesothelioma. No cases of peritoneal mesothelioma have been identified. Prior to 1978, 60 men had died from respiratory cancer other than mesothelioma, compared with 38.25 expected from the mortality experience of all Western Australian males. The incidence of pneumoconiosis and mesothelioma and the mortality from other respiratory cancer all increased with duration of employment, interval from first employment, and level of occupational exposure, indicating a strong relationship between intensity of asbestos exposure and these diseases. The mortality ratio for respiratory cancer, excluding mesothelioma (1.57), was nearly twice that for all nonrespiratory causes of death, suggesting a two-fold increase in mortality from respiratory cancer compared with all Western Australian males. Variation of mortality from respiratory cancer by duration of employment and occupational exposure suggests that at least 30% of respiratory cancer deaths other than mesothelioma may be due to asbestos exposure. The major part of this excess is accounted for by respiratory cancer occurring in men with previously diagnosed pneumoconiosis.}, } @article {pmid7228315, year = {1980}, author = {McDonald, JC}, title = {Asbestos-related disease: an epidemiological review.}, journal = {IARC scientific publications}, volume = {}, number = {30}, pages = {587-601}, pmid = {7228315}, issn = {0300-5038}, mesh = {Asbestos/*adverse effects ; Asbestosis/etiology ; Epidemiologic Methods ; Humans ; Lung Diseases/epidemiology/*etiology ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Mining ; North America ; Occupational Diseases/epidemiology/etiology ; United Kingdom ; }, } @article {pmid7228311, year = {1980}, author = {Ruffie, P and Hirsch, A}, title = {A review of the treatment of diffuse malignant pleural mesothelioma.}, journal = {IARC scientific publications}, volume = {}, number = {30}, pages = {553-557}, pmid = {7228311}, issn = {0300-5038}, mesh = {Asbestos/*adverse effects ; Humans ; Mesothelioma/etiology/*therapy ; Occupational Diseases/etiology/therapy ; Pleural Neoplasms/etiology/*therapy ; Prognosis ; Time Factors ; }, abstract = {When the disease is diagnosed early, pleurectomy or intrapleural inoculation of colloidal radioactive compounds may be effective. However, most mesotheliomas are already diffuse by the time they are diagnosed; and no treatment has been shown to be effective. Metastatic involvement of the chest wall results from any surgical procedure; however, pain may be controlled by pleurectomy and/or external-beam radiotherapy. Of the chemotherapeutic agents tested, doxorubicin appears to be the most promising. Large, cooperative, controlled trials are needed to evaluate the usefulness of one or a combination of the treatment methods described.}, } @article {pmid7228304, year = {1980}, author = {Bohlig, H and Hain, E}, title = {Clinical and radiological observations on asbestos-related pathology.}, journal = {IARC scientific publications}, volume = {}, number = {30}, pages = {497-506}, pmid = {7228304}, issn = {0300-5038}, mesh = {Adult ; Asbestos/*adverse effects ; *Dust ; Environmental Exposure ; Female ; Germany, West ; Humans ; Lung Diseases/*diagnostic imaging/etiology ; Male ; Pleura/diagnostic imaging/pathology ; Pleural Diseases/*diagnostic imaging/etiology ; *Population Surveillance ; Radiography ; }, abstract = {The papers in this session, which are summarized briefly, do not cover the wide range of radiological and clinical problems resulting from inhalation of asbestos dust. Pleural effusions are found in persons exposed occupationally to asbestos, even in the absence of asbestosis, but they are difficult to attribute to such exposure. Asbestosis of the lung shows no striking symptoms and can also be diagnosed only after all other possibilities have been excluded. There are no convincing or striking morphological peculiarities that suggest that an 'asbestos lung cancer' exists. Mesotheliomas of the pleura and of the peritoneum are usually resistant to therapy of any kind, although several possibilities are discussed. Radiological surveillance is presented as being still the most effective and reliable method for medical surveillance of asbestos workers. Circumscribed pleural thickening is benign but a good indicator of exposure to mineral dusts. Diffuse pleural thickening occurs frequently in nonexposed groups and cannot, therefore, be used as an indication of exposure; however, it cannot yet be ruled out as being significant epidemiologically.}, } @article {pmid7221169, year = {1980}, author = {Baris, YI}, title = {[Claude Bernard-Horner's syndrome due to malignant pleural mesothelioma (author's transl)].}, journal = {Revue francaise des maladies respiratoires}, volume = {8}, number = {5}, pages = {349-350}, pmid = {7221169}, issn = {0301-0279}, mesh = {Adult ; Asbestos/adverse effects ; Environmental Exposure ; Female ; Horner Syndrome/*etiology ; Humans ; Male ; Mesothelioma/*complications/etiology ; Middle Aged ; Pleural Neoplasms/*complications/etiology ; }, abstract = {Seven cases of Claude Bernard-Horner's syndrome due to malignant pleural mesothelioma are described. All the patients were middle aged farmers and lived in the rural part of Central Anatolia. Two of them lived in Karain and had been exposed to inhale erionite type zeolite fibres. Hence the other five subjects lived in asbestos deposit areas. Pleural effusion, pleural thickening and nodular pleural lesions were the radiological findings. Rib erosion was found in one case. All the patients had tissue diagnosis by pleural punch biopsy, thoracoscopy or thoracotomy.}, } @article {pmid7187068, year = {1980}, author = {Meyniard, O and Boissonnas, A and Laisne, MJ and Laroche, C and Abelanet, R}, title = {[Chronic pneumonia caused by paraffin oil and pleural modifications: mesothelial hyperplasia and mesothelioma].}, journal = {Revue francaise des maladies respiratoires}, volume = {8}, number = {3}, pages = {259-263}, pmid = {7187068}, issn = {0301-0279}, mesh = {Aged ; Chronic Disease ; Female ; Humans ; Hyperplasia/*chemically induced ; Mesothelioma/*chemically induced ; Oils/*adverse effects ; Paraffin/*adverse effects ; Pleura/*drug effects/pathology ; Pleural Effusion/*complications ; Pneumonia, Aspiration/*chemically induced ; Pneumonia, Lipid/*chemically induced/complications/pathology ; }, abstract = {A 82 years old woman with no past history of cardiac or pulmonary disease or asbestos exposure, but with chronic administration of paraffin oil as laxative, had lipid pneumonia and a primary neoplasic pleural effusion. From the reported case, the authors discuss the possible part of mineral oil as pleural carcinogenic factor (mesothelioma).}, } @article {pmid7016757, year = {1980}, author = {Kannerstein, M}, title = {Recent advances and perspectives relevant to the pathology of asbestos-related diseases in man.}, journal = {IARC scientific publications}, volume = {}, number = {30}, pages = {149-162}, pmid = {7016757}, issn = {0300-5038}, support = {ES-00238/ES/NIEHS NIH HHS/United States ; }, mesh = {Asbestos/*adverse effects/analysis ; Asbestosis/immunology/pathology ; Cocarcinogenesis ; Humans ; Lung Neoplasms/pathology ; Mesothelioma/pathology ; Microscopy, Electron, Scanning ; Peritoneal Neoplasms/pathology ; Pleural Neoplasms/pathology ; Pulmonary Fibrosis/etiology ; Smoking ; }, abstract = {It is apparent that progress is being made in the diagnosis of mesothelioma on the basis of morphological studies. It is also obvious that in almost every area uncertainties and deficiencies still exist. The significance of fibrous substances other than asbestos in the etiology of the various lesions is a field to be explored. The role of pulmonary fibrosis in the pathogenesis of carcinoma of the lung in those exposed to asbestos remains ill-defined. Morphological study of mesothelioma variants and imitators must continue. The accumulation of further ultrastructural data is desirable. Attempts should be made to clarify certain ambiguities in histochemical features. Recently devised staining methods and chemical, immunochemical and immunological diagnostic techniques must be further tried to establish their reliability. The utility of mesothelioma diagnostic panels seems fairly widely accepted, but persistent efforts to reconcile observer variation and to reduce subjectivity are necessary. The pursuit of immunological testing has both theoretical and practical importance. A method for the detection of susceptible persons has long been sought. The value of electron microscopy in the investigation of fibres in relation to carcinogenesis is manifest. Data is accumulating regarding fibre quantity, type and dimensions in relation to the various related lesions. The predominant role of amphiboles in the formation of asbestos bodies appears to be established. Further studies of regional distribution of fibres with their types and sizes in the lung and pleura would seem essential. Whether this will alter the concepts of the significance of exposure as indicated by analysis of the parenchymal component alone is an important question.}, } @article {pmid6453085, year = {1980}, author = {Tait, N}, title = {The effect of differing concepts of the criteria that should be used for the diagnosis of asbestos disease.}, journal = {IARC scientific publications}, volume = {}, number = {30}, pages = {855-859}, pmid = {6453085}, issn = {0300-5038}, mesh = {Asbestosis/economics/*epidemiology/mortality ; Disability Evaluation ; Humans ; Maximum Allowable Concentration ; Mesothelioma/economics/epidemiology/mortality ; Occupational Diseases/economics/etiology/*prevention & control ; Registries ; United Kingdom ; *Workers' Compensation ; }, abstract = {The work of the Society for the Prevention of Asbestosis and Industrial Disease suggests that arbitrary rules, operated for the purpose of deciding which cases may benefit from employment insurance schemes, are adding to the recognized problems connected with the diagnosis of asbestos disease. As a result, statistics are unrealistic and do not include cases which show not only that workers in th asbestos manufacturing industry are at risk, but that asbestos, including chrysotile, affects the health of the community.}, } @article {pmid6266568, year = {1980}, author = {Wagner, JC and Berry, G and Pooley, FD}, title = {Carcinogenesis and mineral fibres.}, journal = {British medical bulletin}, volume = {36}, number = {1}, pages = {53-56}, doi = {10.1093/oxfordjournals.bmb.a071614}, pmid = {6266568}, issn = {0007-1420}, mesh = {Animals ; Asbestos/*adverse effects ; Dose-Response Relationship, Drug ; Glass ; Humans ; Lung Neoplasms/epidemiology/etiology ; Male ; Mesothelioma/epidemiology/etiology ; Minerals/*adverse effects ; Neoplasms/*etiology ; Occupational Diseases/epidemiology ; Rats ; Silicon Dioxide/adverse effects ; United Kingdom ; United States ; }, } @article {pmid4470952, year = {1974}, author = {Smither, WJ}, title = {Asbestos in the workplace and the community.}, journal = {Environmental health perspectives}, volume = {9}, number = {}, pages = {327-329}, pmid = {4470952}, issn = {0091-6765}, mesh = {Air Pollutants ; Air Pollutants, Occupational ; *Asbestos ; Dust ; England ; Environmental Exposure ; Female ; Humans ; Male ; Mesothelioma/*mortality ; Peritoneal Neoplasms/*mortality ; Pleural Neoplasms/*mortality ; }, abstract = {Information developed by Newhouse in a survey of an asbestos factory in London suggests that the risk of mesothelial tumors is strongly related to both the degree and the length of exposure to asbestos dust.}, } @article {pmid4470949, year = {1974}, author = {Churg, J}, title = {Peritoneal mesothelioma.}, journal = {Environmental health perspectives}, volume = {9}, number = {}, pages = {317-318}, pmid = {4470949}, issn = {0091-6765}, mesh = {Asbestos/adverse effects ; Diagnosis, Differential ; Environmental Exposure ; Humans ; *Mesothelioma/diagnosis/etiology ; *Peritoneal Neoplasms/diagnosis/etiology ; }, } @article {pmid4470947, year = {1974}, author = {Selikoff, IJ}, title = {Epidemiology of gastrointestinal cancer.}, journal = {Environmental health perspectives}, volume = {9}, number = {}, pages = {299-305}, pmid = {4470947}, issn = {0091-6765}, mesh = {Asbestos/adverse effects ; Asbestosis/mortality ; Carcinoma, Bronchogenic/mortality ; Environmental Exposure ; Gastrointestinal Neoplasms/*epidemiology/etiology/mortality ; Humans ; Lung Neoplasms/mortality ; Male ; Mesothelioma/mortality ; Pleural Neoplasms/mortality ; Smoking ; United States ; }, abstract = {Some 99,000 new cases of cancer of the colon are expected next year, an incidence rate higher than that for both cancer of the lung and cancer of the breast. Evidence from geographic pathology suggests that some environmental factors play a strong role in its etiology. Data obtained in the 1959 survey of one million people by the American Cancer Society and followed since, has failed to show correlation with any of the large number of factors listed. It is suggested that the etiology is one of multiple factors. The synergistic effect of exposure to asbestos and cigarette smoking in the production of bronchogenic carcinoma is demonstrated by data on cohorts of insulation workers. There was also a modest increase in the number of deaths from gastrointestinal cancer in asbestos workers, but smoking did not seem to act in synergistic fashion at that site, except perhaps in the esophagus. Deaths from cancer occurred almost entirely after a period of 20 years or more from initial exposure. The death rate from cancer tended to increase with duration of exposure, but a distinct rise over the expected was seen in those who had been exposed less than one year to amosite dust.}, } @article {pmid4470945, year = {1974}, author = {Heppleston, AG}, title = {Correlation between the tissue response and asbestos fiber content.}, journal = {Environmental health perspectives}, volume = {9}, number = {}, pages = {295-296}, pmid = {4470945}, issn = {0091-6765}, mesh = {Asbestos/*analysis ; Asbestosis/metabolism/*pathology ; Humans ; Lung/analysis/pathology ; Pulmonary Fibrosis/metabolism/*pathology ; }, abstract = {Asbestos fiber concentration increases in proportion to the degree of pulmonary fibrosis as far as the moderate grade. No such correlation occurs with severe asbestosis, nor with the morphological form which the fibrosis assumes, and here secondary factors may be concerned. Electron microscopy suggests that optically visible fibers constitute a reasonably constant proportion of the total irrespective of the pathological reaction. Light microscopy may thus afford a guide to the total asbestos concentration. Finally, the development of mesothelioma, whether of the pleura or the peritoneum, appears to be unrelated to the concentration of coated or uncoated asbestos fibers residing in the lung.}, } @article {pmid4470936, year = {1974}, author = {Webster, I}, title = {The ingestion of asbestos fibers.}, journal = {Environmental health perspectives}, volume = {9}, number = {}, pages = {199-202}, pmid = {4470936}, issn = {0091-6765}, mesh = {Animals ; *Asbestos/analysis ; Diet ; *Digestive System/analysis ; Feces/analysis ; Gastrointestinal Neoplasms ; Humans ; Intestinal Mucosa/analysis ; Iron/analysis ; Macrophages/analysis ; Mesothelioma ; Papio ; Peritoneal Neoplasms ; Sewage ; Water Pollution, Chemical ; Water Supply ; }, abstract = {Feeding of baboons with crocidolite showed small numbers of asbestos needles 0.5-1 mum in ashed tissue of the gut wall, which probably came from iron-containing macrophages. It is suggested that pleural plaques and hyaline nodules in the peritoneum represent a hypersensitivity reaction to ferritin protein coating on asbestos fibers. In South Africa only a few peritoneal mesotheliomas come from the asbestos areas, and the incidence of gastrointestinal carcinomas is no greater than normal. Intrapleural and intraperitoneal injection produces unrealistic situations. Calcium salts are deposited on asbestos cement pipes from hard water and organic material from soft water. It is difficult to envisage asbestos contamination of the water so reticulated.}, } @article {pmid4470929, year = {1974}, author = {Bignon, J and Sebastien, P and Jaurand, MC and Hem, B}, title = {Microfiltration method for quantitative study of fibrous particles in biological specimens.}, journal = {Environmental health perspectives}, volume = {9}, number = {}, pages = {155-160}, pmid = {4470929}, issn = {0091-6765}, mesh = {Adult ; Aged ; Asbestos/*analysis ; Asbestosis/diagnosis ; Carcinoma/analysis ; Diagnosis, Differential ; Environmental Exposure ; Gastric Juice/*analysis ; Humans ; Lung/*analysis ; Lung Neoplasms/analysis ; Male ; Mesothelioma/analysis ; Middle Aged ; Occupations ; Pleural Neoplasms/analysis ; Pulmonary Fibrosis/metabolism ; Sputum/*analysis ; *Ultrafiltration ; }, abstract = {Counting coated and uncoated inorganic fibers in sputum has been used to investigate the level of environmental or occupational asbestos exposure and the concentration of fibrous dusts in human lung. Inorganic fibers in sputum were counted by light microscopy after chemical digestion and microfiltration processing. The same method was used for processing gastric juice and lung tissue. There were no ferruginous bodies (FB) in sputum from 49 patients without any asbestos exposure. The study of sputum from 125 patients with various asbestos exposure pointed out a high correlation between the number of FB in sputum and the level of asbestos exposure. These 125 patients were classified into three groups according to the type of their asbestos occupational hazard: group I, raw asbestos workers; group II, workers manufacturing asbestos products; group III, workers with mixed industrial dust exposure. For these three groups, the mean number of FB in sputum was 100, 10, and 1, respectively. The comparison of the FB content of sputum and lung parenchyma showed the absence of FB in sputum when the concentration of FB in lung parenchyma was under 1000/cm(3) of lung parenchyma; above this concentration the number of FB in sputum was in good correlation with fiber concentration in lung parenchyma. A preliminary study with the use of gastric juice showed that gastric juice is a less sensitive sample for evaluating fiber concentration in lung. The microfiltration method for the counting of uncoated fibers gave results as accurate as those in the centrifugation method.}, } @article {pmid4470928, year = {1974}, author = {Le Bouffant, L}, title = {Investigation and analysis of asbestos fibers and accompanying minerals in biological materials.}, journal = {Environmental health perspectives}, volume = {9}, number = {}, pages = {149-153}, doi = {10.1289/ehp.749149}, pmid = {4470928}, issn = {0091-6765}, mesh = {Asbestos/*analysis ; Hot Temperature ; Humans ; Hydrochloric Acid ; Lung/chemistry ; Mesothelioma/*chemistry ; Microscopy, Electron ; Minerals/*analysis ; Pleura/chemistry ; Pleural Neoplasms/*chemistry ; X-Ray Diffraction ; }, abstract = {A method is described for isolating asbestos fibers contained in biological tissues. It consists in incinerating the biological material in activated oxygen at 150 degrees C, and attacking the ash by 1N HC1 for 18 hr. The residue is then filtered on a membrane covered with a carbon film. Electron microscope examination of the deposit makes it possible to determine fiber concentrations when the weight or volume of primary material is known, and to make size analyses. By x-ray diffraction, the mineralogical nature of the asbestos is determined by comparison with an aluminum reference diagram. For x-ray diffraction, a micromethod is used, with an ash sample of about 10 mug. These techniques are used for identifying and counting asbestos fibers in small fragments of lungs or other organs. It was found that asbestos fibers generally go along with other minerals which may be abundant. Most fibers found in lung are less than 5 mum long. Counts on lungs of asbestos workers give concentrations often greater than 10(7) particles per gram of dry tissue. The evolution of inhaled chrysotile seems to be different from that of amphiboles. In the case of pleural mesothelioma, a comparison of fibers within the tumor with fibers in the adjacent parenchyma shows only slight differences in the particle sizes, but marked differences in their nature, with a chrysotile enrichment in the pleural zone. Pleural plaques were analyzed in the same way. After decalcification, many small sized asbestos fibers were found. The same technique is now being used for determining ingested particles. A great number of observations concerning fiber counts, their nature and sizes, and the presence of various clays minerals will be necessary to establish the role of the different factors in the formation of lesions caused by the inhalation or the ingestion of asbestos fibers.}, } @article {pmid4470927, year = {1974}, author = {Fondimare, A and Desbordes, J}, title = {Asbestos bodies and fibers in lung tissues.}, journal = {Environmental health perspectives}, volume = {9}, number = {}, pages = {147-148}, doi = {10.1289/ehp.749147}, pmid = {4470927}, issn = {0091-6765}, mesh = {Asbestos/*analysis ; Asbestosis/metabolism ; Humans ; Lung/*analysis ; Mesothelioma/analysis ; Microscopy, Electron ; Pleura/analysis ; Pleural Neoplasms/analysis ; }, abstract = {It is suggested that the ratio of asbestos bodies observable by light microscopy to asbestos fibers counted by electron microscopy be examined in a series of cases of asbestosis of varying severity. If the ratio is reasonably constant an estimate of fiber content could be made from the more easily conducted count of asbestos bodies by light microscopy.}, } @article {pmid4377876, year = {1974}, author = {Pott, F and Huth, F and Friedrichs, KH}, title = {Tumorigenic effect of fibrous dusts in experimental animals.}, journal = {Environmental health perspectives}, volume = {9}, number = {}, pages = {313-315}, pmid = {4377876}, issn = {0091-6765}, mesh = {Abdominal Neoplasms/*etiology ; Animals ; Asbestos/adverse effects ; Calcium/adverse effects ; *Dust ; Glass ; Injections, Intraperitoneal ; Mesothelioma/*etiology ; Rats ; Silicon Dioxide/adverse effects ; Sulfates ; Talc/adverse effects ; }, abstract = {Fibrous dusts (chrysotile, glass fibers, nemalite, palygorscite, and gypsum) and granular dusts (actinolite, biotite, hematite, pectolite, sanidine, and talcum) were injected intraperitoneally into rats. The fibrous dusts (other than gypsum) resulted in a high incidence of mesothelioma (30 - 67%). Gypsum produced only 5% and granular dusts none at all. It is suggested that the fibrous shape leads to a high multiplication rate of cells and predisposes to tumor formation. Fibrosis, in the other hand, does not so predispose. Milled chrysotile with 99.8% fibers than 5 mum in length are carcinogenic in our experience. The carcinogenicity of glass fibers in our experiments may have significance for occupational situations.}, } @article {pmid4377872, year = {1974}, author = {Holt, PF}, title = {Small animals in the study of pathological effects of asbestos.}, journal = {Environmental health perspectives}, volume = {9}, number = {}, pages = {205-211}, pmid = {4377872}, issn = {0091-6765}, mesh = {Animals ; Asbestos/*adverse effects/metabolism ; Carbon/adverse effects ; Dust ; Guinea Pigs ; Lung/metabolism ; Lymph Nodes/metabolism ; Macrophages/metabolism ; Neoplasms/etiology ; Phagocytosis ; Pulmonary Fibrosis/etiology ; Silicon Dioxide/adverse effects ; }, abstract = {The main pathological effects attributed to asbestos are carcinogenesis and fibrogenesis. Statistical studies have shown that asbestos workers may expect a higher morbidity not only from cancer of the lung and mesothelioma but also from cancer at other sites. Carcinomas have been reported in animals following the injection of asbestos, but the production of carcinomas by inhaled asbestos is less easy to demonstrate; most examples of experimental carcinogenesis with asbestos have been produced in rats. Rats and man react differently to asbestos in that rats do not produce asbestos bodies. The fibrosis that follows inhalation of asbestos has been frequently described, but studies with specific pathogen free animals have shown that, like the fibrosis that may follow the inhalation of silica dust, gross fibrosis involving the production of abnormal amount of collagen probably requires the intervention of infection as well as asbestos. Because of the difficulties encountered in the direct investigation of carcinogenesis and fibrogenesis resulting from the inhalation of asbestos, attention has been directed to the mechanisms by which the lung is able to protect itself against these fibrous dusts. While non-fibrous dusts and short fibers can be ingested by macrophages and removed via the bronchus, the long fibers that may also reach the alveolar regions may not be removed by this mechanism. The probability that a fiber may reach the alveoli depends largely on the fiber diameter and only to a small extent on the fiber length, so that, for example, fibers 100 mum long may reach the alveoli of a guinea pig. These long fibers may become coated with a ferroprotein derived from hemoglobin to form an asbestos body and, after morphological changes, the asbestos body may be broken up, the fragments ingested by macrophages and dissolved. The lung is thus cleared of asbestos. In the guinea pig lung, consolidated areas from which the asbestos has disappeared shows signs of return to normal. THIS CLEARANCE MECHANISM IS INHIBITED BY OTHER FACTORS: quartz dust may almost completely inhibit asbestos body formation; tobacco smoke has a considerable effect, and even very heavy loads of carbon may act similarly. The normal lung appears able to efficiently eliminate small loads of both nonfibrous and fibrous dust, including the carcinogenic asbestos fibers. The capacity is not unlimited, however, and when the load is heavy there is a much greater probability that fibers will not be detoxicated. In addition, other factors such as silica dust and tobacco smoke may remove the protective mechanism in the lungs.}, } @article {pmid4422307, year = {1974}, author = {Polednak, AP}, title = {Latency periods in neoplastic diseases.}, journal = {American journal of epidemiology}, volume = {100}, number = {5}, pages = {354-356}, doi = {10.1093/oxfordjournals.aje.a112045}, pmid = {4422307}, issn = {0002-9262}, mesh = {Age Factors ; Air Pollution ; Asbestos/poisoning ; Carcinogens ; Cell Transformation, Neoplastic ; Coitus ; DNA ; Environmental Exposure ; Female ; Genetic Code ; Humans ; Infections ; Lung Diseases/complications ; Lung Neoplasms/etiology ; Male ; Mesothelioma/chemically induced ; *Models, Biological ; Neoplasms/*etiology/genetics ; Smoking/complications ; Time Factors ; Uterine Cervical Neoplasms/etiology ; }, } @article {pmid4377581, year = {1974}, author = {Cooper, D}, title = {Malignant mesothelioma invading the spinal canal.}, journal = {Postgraduate medical journal}, volume = {50}, number = {589}, pages = {718-723}, pmid = {4377581}, issn = {0032-5473}, mesh = {Adenocarcinoma, Bronchiolo-Alveolar/pathology ; Aged ; Humans ; Lung Neoplasms/*pathology ; Male ; Mesothelioma/*pathology ; Neoplasm Metastasis ; Paraplegia/etiology ; Pleural Neoplasms/complications/*pathology ; Spinal Cord Neoplasms/*pathology ; }, abstract = {A case of diffuse malignant pleural mesothelioma presenting as acute paraplegia is described. Autopsy revealed the presence of metastatic tumour within the spinal cord. An alveolar cell carcinoma coexisting with the mesothelioma and giving a distinct histological pattern was also present. There was no histological evidence of asbestos exposure.}, } @article {pmid4548573, year = {1974}, author = {Bamler, KJ and Maassen, W}, title = {[The percentage of benign and malign pleura-tumors among the patients of a clinic of lung surgery with special consideration of the malign pleuramesothelioma and its radical treatment, including results of a diaphragma substitution of preserved dura mater (author's transl)].}, journal = {Thoraxchirurgie, vaskulare Chirurgie}, volume = {22}, number = {5}, pages = {386-391}, doi = {10.1055/s-0028-1102794}, pmid = {4548573}, issn = {0040-6384}, mesh = {Aged ; Asbestos ; Diaphragm/*surgery ; Dura Mater/*transplantation ; Female ; Follow-Up Studies ; Hemangiopericytoma ; Humans ; Male ; Mesothelioma/complications/diagnostic imaging/pathology/*surgery ; Methods ; Middle Aged ; Pleural Effusion/complications/diagnostic imaging ; Pleural Neoplasms/complications/diagnostic imaging/pathology/*surgery ; Pneumonectomy ; Radiography ; Transplantation, Homologous ; }, } @article {pmid4455505, year = {1974}, author = {Reeves, AL and Puro, HE and Smith, RG}, title = {Inhalation carcinogenesis from various forms of asbestos.}, journal = {Environmental research}, volume = {8}, number = {2}, pages = {178-202}, doi = {10.1016/0013-9351(74)90050-4}, pmid = {4455505}, issn = {0013-9351}, mesh = {Animals ; *Asbestos ; Atmosphere Exposure Chambers ; Bronchial Neoplasms/chemically induced ; *Carcinogens ; Carcinoma, Papillary/chemically induced ; Carcinoma, Squamous Cell/chemically induced ; Dust ; Environmental Exposure ; Female ; Fibrosarcoma/chemically induced ; Gerbillinae ; Guinea Pigs ; Lung Neoplasms/chemically induced ; Male ; Mesothelioma/chemically induced ; Mice ; Pleural Neoplasms/chemically induced ; Rabbits ; Rats ; Respiratory Tract Neoplasms/*chemically induced ; Species Specificity ; }, } @article {pmid4497349, year = {1974}, author = {Fokkens, W}, title = {[Cancer as an occupational disease].}, journal = {Tijdschrift voor ziekenverpleging}, volume = {27}, number = {33}, pages = {871-881}, pmid = {4497349}, mesh = {Asbestos/poisoning ; *Carcinogens ; Environmental Exposure ; Female ; Hemangiosarcoma/chemically induced ; Humans ; Leukemia/chemically induced ; Liver Neoplasms/chemically induced ; Lung Neoplasms/chemically induced ; Male ; Mesothelioma/chemically induced ; Neoplasms/*chemically induced ; Occupational Diseases/*chemically induced ; Paranasal Sinus Neoplasms/chemically induced ; Scrotum ; Urogenital Neoplasms/chemically induced ; }, } @article {pmid4142974, year = {1974}, author = {}, title = {Editorial: Biological effects of asbestos.}, journal = {Lancet (London, England)}, volume = {2}, number = {7882}, pages = {706}, pmid = {4142974}, issn = {0140-6736}, mesh = {Animals ; Asbestos/*adverse effects ; Asbestosis/etiology ; Bronchial Neoplasms/chemically induced ; Humans ; Mesothelioma/chemically induced ; Occupational Diseases/chemically induced ; }, } @article {pmid4852731, year = {1974}, author = {Lillington, GA and Jamplis, RW and Differding, JR}, title = {Letter: Conjugal malignant mesothelioma.}, journal = {The New England journal of medicine}, volume = {291}, number = {11}, pages = {583-584}, doi = {10.1056/NEJM197409122911117}, pmid = {4852731}, issn = {0028-4793}, mesh = {Asbestos/adverse effects ; Environmental Exposure ; Female ; Humans ; Male ; Mesothelioma/*genetics ; Middle Aged ; Occupational Diseases ; Pleural Neoplasms/*genetics ; }, } @article {pmid4419487, year = {1974}, author = {Timbrell, V}, title = {Proceedings: The physicist's approach to asbestos cancers.}, journal = {Clinical science and molecular medicine}, volume = {47}, number = {3}, pages = {12P}, doi = {10.1042/cs047012p}, pmid = {4419487}, issn = {0301-0538}, mesh = {Asbestos/*adverse effects ; Asbestosis/etiology ; Humans ; Injections ; Lung Neoplasms/chemically induced ; Mesothelioma/chemically induced ; Neoplasms/*chemically induced ; Particle Size ; }, } @article {pmid4419326, year = {1974}, author = {Gilson, JC}, title = {Proceedings: Biological effects of asbestos. Unanswered questions posed by epidemiological studies.}, journal = {Clinical science and molecular medicine}, volume = {47}, number = {3}, pages = {11P}, doi = {10.1042/cs047011pa}, pmid = {4419326}, issn = {0301-0538}, mesh = {Asbestos/*adverse effects ; Asbestosis/*epidemiology ; Environmental Exposure ; Humans ; Mesothelioma/chemically induced ; Neoplasms/chemically induced ; Occupational Diseases/chemically induced ; }, } @article {pmid4419325, year = {1974}, author = {Wagner, JC}, title = {Proceedings: Biological effects of asbestos. Experimental and future studies.}, journal = {Clinical science and molecular medicine}, volume = {47}, number = {3}, pages = {12P}, pmid = {4419325}, issn = {0301-0538}, mesh = {Animals ; Asbestos/adverse effects ; *Asbestosis ; Lung Neoplasms/chemically induced ; Mesothelioma/chemically induced ; Rats ; }, } @article {pmid4835180, year = {1974}, author = {Gross, P}, title = {Is short-fibered asbestos dust a biological hazard?.}, journal = {Archives of environmental health}, volume = {29}, number = {2}, pages = {115-117}, doi = {10.1080/00039896.1974.10666544}, pmid = {4835180}, issn = {0003-9896}, mesh = {Animals ; Asbestos/administration & dosage/*toxicity ; Asbestosis/etiology ; Cricetinae ; Dust ; Environmental Exposure ; Fibrosarcoma/chemically induced ; Gastrointestinal Neoplasms/chemically induced ; Guinea Pigs ; Humans ; Injections, Intraperitoneal ; Male ; Mesothelioma/chemically induced ; Methods ; Neoplasms/chemically induced ; Occupational Diseases/chemically induced ; Particle Size ; Peritoneal Neoplasms/chemically induced ; Pleural Neoplasms/chemically induced ; Pulmonary Fibrosis/chemically induced ; Rats ; }, } @article {pmid4280028, year = {1974}, author = {Gasson, EE}, title = {Asbestos in industry. 1.}, journal = {Occupational health; a journal for occupational health nurses}, volume = {26}, number = {8}, pages = {298-306}, pmid = {4280028}, issn = {0029-7917}, mesh = {*Asbestos ; Asbestosis ; Callosities/chemically induced ; Environmental Exposure ; Humans ; Lung Neoplasms/chemically induced ; Mesothelioma/chemically induced ; *Occupational Medicine ; Peritoneal Neoplasms/chemically induced ; Pleural Neoplasms/chemically induced ; }, } @article {pmid4607166, year = {1974}, author = {McCullagh, SF}, title = {The biological effects of asbestos.}, journal = {The Medical journal of Australia}, volume = {2}, number = {2}, pages = {45-49}, pmid = {4607166}, issn = {0025-729X}, mesh = {Animals ; Asbestos/*adverse effects/standards/toxicity ; Asbestosis/diagnosis/diagnostic imaging/etiology ; Environmental Exposure ; Environmental Health ; Female ; Humans ; Lung Neoplasms/chemically induced ; Male ; Mesothelioma/chemically induced ; Mice ; Pleural Diseases/etiology ; Radiography ; Rats ; Smoking/complications ; United Kingdom ; United States ; Urban Population ; }, } @article {pmid4602756, year = {1974}, author = {Sarrazin, W}, title = {[Health hazards due to inhalation of asbestos fibres (author's transl)].}, journal = {Praxis der Pneumologie}, volume = {28}, number = {7}, pages = {370-388}, pmid = {4602756}, issn = {0032-7069}, mesh = {Adult ; Asbestos/*adverse effects ; Asbestosis/etiology ; Automobile Driving ; Dust ; Environmental Exposure ; Environmental Health ; Environmental Pollution ; Germany, West ; Humans ; Industry ; Legislation, Medical ; Lung Neoplasms/chemically induced ; Male ; Mesothelioma/chemically induced ; Mining ; Occupations ; }, } @article {pmid4601063, year = {1974}, author = {Rom, WN and Palmer, PE}, title = {The spectrum of asbestos-related diseases.}, journal = {The Western journal of medicine}, volume = {121}, number = {1}, pages = {10-21}, pmid = {4601063}, issn = {0093-0415}, mesh = {Asbestos/adverse effects ; *Asbestosis/complications/diagnostic imaging/epidemiology/pathology/physiopathology/prevention & control ; Calcinosis/complications/etiology ; Canada ; Carcinogens ; Environmental Pollution ; Humans ; Lung/pathology ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Occupational Medicine ; Pleural Diseases/etiology ; Pleural Neoplasms/etiology ; Radiography ; South Africa ; Spirometry ; United States ; Zimbabwe ; }, abstract = {Diseases caused by exposure to asbestos are prime examples of environmentally-related illnesses. Asbestos produces asbestosis from large exposures over short latent periods; it acts as a carcinogen from small exposures over long latent periods; and it induces mesothelioma with minute exposures. Its presence as the magic mineral is ubiquitous in our modern society.}, } @article {pmid4444447, year = {1974}, author = {Jones, JS}, title = {Pathological and environmental aspects of asbestos-associated diseases.}, journal = {Medicine, science, and the law}, volume = {14}, number = {3}, pages = {152-158}, doi = {10.1177/002580247401400303}, pmid = {4444447}, issn = {0025-8024}, mesh = {Asbestos/*adverse effects ; Asbestosis/*etiology ; Environmental Exposure ; Humans ; Lung Neoplasms/*chemically induced ; Mesothelioma/*chemically induced ; Peritoneal Neoplasms/*chemically induced ; Pleural Neoplasms/*chemically induced ; }, } @article {pmid4441940, year = {1974}, author = {Leménager, J and Bénard, Y and Lalaude, J}, title = {[Pleural pathology of asbestos].}, journal = {Les Cahiers de medecine}, volume = {15}, number = {6}, pages = {289-296}, pmid = {4441940}, issn = {0010-0978}, mesh = {Asbestosis/*complications ; Environmental Exposure ; Humans ; Mesothelioma/*etiology ; Pleura/pathology ; Pleural Neoplasms/*etiology ; }, } @article {pmid4369664, year = {1974}, author = {Moigneteau, C and Guillement, JM and Gontier, F}, title = {[Respiratory diseases caused by asbestos].}, journal = {La semaine des hopitaux : organe fonde par l'Association d'enseignement medical des hopitaux de Paris}, volume = {50}, number = {27}, pages = {1905-1908}, pmid = {4369664}, mesh = {Asbestosis/*complications ; Bronchial Diseases/*etiology ; Calcinosis/etiology ; Humans ; Mesothelioma/etiology ; Pleural Diseases/*etiology ; Pleural Neoplasms/etiology ; Pleurisy/etiology ; Pulmonary Fibrosis/etiology ; }, } @article {pmid4834411, year = {1974}, author = {Davis, JM}, title = {Histogenesis and fine structure of peritoneal tumors produced in animals by injections of asbestos.}, journal = {Journal of the National Cancer Institute}, volume = {52}, number = {6}, pages = {1823-1837}, doi = {10.1093/jnci/52.6.1823}, pmid = {4834411}, issn = {0027-8874}, mesh = {Animals ; *Asbestos ; *Carcinogens ; Cell Membrane ; Collagen/analysis ; Connective Tissue Cells ; Cytoplasm ; Diaphragm/pathology ; Epithelial Cells ; Mesothelioma/*chemically induced/pathology ; Mice ; Mice, Inbred BALB C ; Microscopy, Electron ; Neoplasms, Experimental/chemically induced/pathology ; Peritoneal Neoplasms/*chemically induced/pathology ; Reticulin/analysis ; }, } @article {pmid4831474, year = {1974}, author = {Zielhuisen, RL and Versteeg, JP}, title = {[Information on the etiology of occupational diseases].}, journal = {Nederlands tijdschrift voor geneeskunde}, volume = {118}, number = {22}, pages = {825-828}, pmid = {4831474}, issn = {0028-2162}, mesh = {Adult ; Aged ; Asbestos ; Female ; Humans ; Male ; Mesothelioma/etiology ; Middle Aged ; Occupational Diseases/*etiology ; Pleural Neoplasms/etiology ; }, } @article {pmid4851473, year = {1974}, author = {Lewinsohn, HC}, title = {Early malignant changes in pleural plaques due to asbestos exposure: a case report.}, journal = {British journal of diseases of the chest}, volume = {68}, number = {2}, pages = {121-127}, doi = {10.1016/0007-0971(74)90024-2}, pmid = {4851473}, issn = {0007-0971}, mesh = {Asbestos/*poisoning ; Asbestosis/complications/pathology ; Autopsy ; Bronchitis/complications ; Chronic Disease ; Environmental Exposure ; Humans ; Hypertension, Pulmonary/complications ; Male ; Mesothelioma/*chemically induced/pathology ; Middle Aged ; Pleura/pathology ; Pleural Neoplasms/*chemically induced/pathology ; Pneumoconiosis/diagnosis ; }, } @article {pmid4835804, year = {1974}, author = {McLachlan, MS and Wagner, JC}, title = {Radiological diagnosis of crocidolite induced pleural mesotheliomata in the rat.}, journal = {British journal of experimental pathology}, volume = {55}, number = {2}, pages = {164-168}, pmid = {4835804}, issn = {0007-1021}, mesh = {Animals ; Asbestos ; Asbestosis/complications ; Female ; Injections ; Male ; Mesothelioma/chemically induced/*diagnostic imaging/pathology ; Pleural Neoplasms/chemically induced/*diagnostic imaging/pathology ; Radiography ; Time Factors ; }, abstract = {Crocidolite asbestos dust was inoculated intrapleurally in 36 rats. Chest radiographs were obtained up to 120 weeks after inoculation. Radiological and pathological observations were compared. In 3 animals, in which mesotheliomata were suspected radiologically, no evidence of malignancy was observed on histological examination. A radiological diagnosis suggesting probable or definite malignancy was made in all 7 animals with histologically proven mesotheliomata.}, } @article {pmid4830768, year = {1974}, author = {Greenberg, M and Davies, TA}, title = {Mesothelioma register 1967-68.}, journal = {British journal of industrial medicine}, volume = {31}, number = {2}, pages = {91-104}, pmid = {4830768}, issn = {0007-1072}, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Asbestos ; Asbestosis/complications ; Child ; Child, Preschool ; England ; Environmental Exposure ; Female ; Humans ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Diseases/epidemiology ; Peritoneal Neoplasms/epidemiology ; Pleural Neoplasms/epidemiology ; Registries ; Scotland ; Sex Factors ; Wales ; }, abstract = {Greenberg, M., and Lloyd Davies, T. A. (1974).British Journal of Industrial Medicine,31, 91-104. Mesothelioma Register 1967-68. A register of mesothelioma cases is maintained by the Department of Employment, Medical Services Division (now Employment Medical Advisory Service). This paper describes an investigation of 413 notifications to the Register in 1967-68 from England and Wales and Scotland. Cases were regarded as `definite' when histological confirmation of diagnosis had been obtained, either by hospital pathologists, or by the UICC Panel of Pathologists, to whom pathological material was submitted whenever possible. Two hundred and forty-six cases were accepted as `definite' and 76 cases were regarded as `definitely not' mesothelioma. The remainder were classified as `undecided' or `insufficient pathological material'. Thirty-five of the 76 cases definitely not mesothelioma had nevertheless been so described on death certificates. The investigation carried out covers clinical aspects, survival, and evidence of exposure to asbestos. Twelve per cent of definite mesotheliomata were of peritoneal origin. The age range was 21 to 87 years, but, in general, mesothelioma occured at an earlier age than `carcinoma of bronchus and lung' or `all malignant tumours' in the Registrar General's statistical mortality tables. Concomitant asbestosis and the finding of asbestos bodies or pleural plaques occured as frequently in those cases classified as definitely not mesothelioma as in confirmed cases. Occupational exposure to asbestos was found in 68% of definite cases, apparently significantly more frequently than in those definitely not mesothelioma, but there was observer bias. The interval between the first exposure and death from mesothelioma exceeded 25 years in 85% of cases but was only three and a half years in one case. The duration of exposure varied widely: in 12% of cases it was under five years. The type of asbestos could be ascertained in so few cases that it was impossible to asses the rôle of crocidolite in aetiology. There were 38 definite cases in which no history of any exposure to asbestos could be obtained. Definite mesotheliomata showed marked clustering in areas where there is substantial industrial use of asbestos. Whether this should be interpreted as evidence of causation or an effect of heightened awareness in these areas cannot be deduced from this study. Evidence is quoted suggesting that the observed annual incidence of approximately 120 definite mesotheliomata in England, Scotland, and Wales may considerably understate the true prevalence.}, } @article {pmid4830762, year = {1974}, author = {Meurman, LO and Kiviluoto, R and Hakama, M}, title = {Mortality and morbidity among the working population of anthophyllite asbestos miners in Finland.}, journal = {British journal of industrial medicine}, volume = {31}, number = {2}, pages = {105-112}, pmid = {4830762}, issn = {0007-1072}, mesh = {Adolescent ; Adult ; Aged ; *Asbestos ; Asbestosis/epidemiology ; Cough/epidemiology ; Dyspnea/epidemiology ; Finland ; Gastrointestinal Neoplasms/epidemiology ; Humans ; Lung Neoplasms/epidemiology ; Male ; Mesothelioma/epidemiology ; Middle Aged ; *Mining ; Occupational Diseases/*epidemiology/mortality ; Smoking/epidemiology ; Tuberculosis, Pulmonary/epidemiology ; }, abstract = {Meurman, L. O., Kiviluoto, R., and Hakama, M. (1974).British Journal of Industrial Medicine,31, 105-112. Mortality and morbidity among the working population of anthophyllite asbestos miners in Finland. A study has been made in Finland of the effects of anthophyllite asbestos on mortality and morbidity of 1 092 asbestos workers first employed at two mines between 1936 and 1969; 95% of workers were traced, 248 of whom had died. A similar number of age-sex-matched controls was selected from a township 60 km from the mines. The causes of death included an excess due to lung cancer and asbestosis, but cancers of the digestive system occurred in equal frequency, and neither the cases nor controls had any confirmed mesotheliomas. Assuming a multiplicative effect of asbestos and smoking, the relative risk of lung cancer was 17 for an asbestos worker who smokes in terms of a non-exposed non-smoker. The corresponding figures were 12 for a smoker without asbestos exposure and 1·4 for an asbestos worker who did not smoke. More heavy smokers were found among the asbestos workers than among the controls. A threefold excess of dyspnoea and a twofold excess of cough were recorded for the asbestos workers compared with the controls after adjustment for smoking.}, } @article {pmid4826587, year = {1974}, author = {Shabad, LM and Pylev, LN and Krivosheeva, LV and Kulagina, TF and Nemenko, BA}, title = {Experimental studies on asbestos carcinogenicity.}, journal = {Journal of the National Cancer Institute}, volume = {52}, number = {4}, pages = {1175-1187}, doi = {10.1093/jnci/52.4.1175}, pmid = {4826587}, issn = {0027-8874}, mesh = {Animals ; Asbestos/analysis/*toxicity ; Benzopyrenes/analysis/toxicity ; *Carcinogens ; Carcinoma/*chemically induced ; Female ; Injections ; Lung/drug effects ; Lung Neoplasms/*chemically induced/pathology ; Male ; Mesothelioma/*chemically induced/pathology ; Neoplasm Transplantation ; Neoplasms, Experimental/chemically induced ; Precancerous Conditions/*chemically induced ; Rats ; Sarcoma/*chemically induced ; Sarcoma, Experimental/chemically induced ; Transplantation, Homologous ; USSR ; }, } @article {pmid4827597, year = {1974}, author = {Bianchi, C and Pegan, M and Carluccio, L}, title = {[Frequency of pulmonary asbestos bodies in autopsy material in Trieste. I].}, journal = {Minerva medica}, volume = {65}, number = {21}, pages = {1141-1143}, pmid = {4827597}, issn = {0026-4806}, mesh = {Aged ; *Asbestos ; Asbestosis/*complications/epidemiology/pathology ; Autopsy ; Female ; *Foreign Bodies ; Humans ; Italy ; *Lung/pathology ; Male ; Mesothelioma/complications ; Middle Aged ; Pleural Neoplasms/complications ; }, } @article {pmid4838100, year = {1974}, author = {Fondimare, A and Desbordes, J and Perrotey, J and Tayot, J and Ernoult, JL}, title = {[Semi-quantitative study of asbestos dust in 14 cases of pleural mesothelioma].}, journal = {Archives d'anatomie pathologique}, volume = {22}, number = {1}, pages = {55-60}, pmid = {4838100}, issn = {0003-9608}, mesh = {Asbestos/*isolation & purification ; Asbestosis/complications ; Autopsy ; Humans ; Lung/*pathology ; Mesothelioma/complications/*pathology ; Microscopy, Electron ; Pleural Neoplasms/complications/*pathology ; }, } @article {pmid4364384, year = {1974}, author = {Wagner, JC and Berry, G and Skidmore, JW and Timbrell, V}, title = {The effects of the inhalation of asbestos in rats.}, journal = {British journal of cancer}, volume = {29}, number = {3}, pages = {252-269}, pmid = {4364384}, issn = {0007-0920}, mesh = {Adenocarcinoma/etiology ; Adenocarcinoma, Bronchiolo-Alveolar/etiology ; Adenoma/etiology ; Animals ; Asbestosis/*complications/pathology ; Carcinoma, Squamous Cell/etiology ; Dose-Response Relationship, Drug ; Dust ; Environmental Exposure ; Female ; Histocytochemistry ; Lung Neoplasms/*etiology/pathology ; Mammary Neoplasms, Experimental/etiology ; Mesothelioma/etiology ; Microscopy, Electron ; Neoplasm Metastasis ; Neoplasms, Experimental/etiology ; Rats ; Time Factors ; }, abstract = {Two experiments in which SPF Wistar rats were exposed by inhalation to dust clouds of the UICC standard reference samples for periods of between one day and 2 years are described. All the samples of asbestos produced asbestosis which continued to progress after removal from exposure but only a little fibrosis was observed in control rats. Lung tumours, ranging in severity from adenomata to squamous carcinomata, were produced by all samples but in the controls there were only a few adenomata and none of the more serious tumours. Of the 20 tumours which metastasized, 16 occurred after exposure to one or other of the 2 chrysotile samples. In addition, a total of 11 mesotheliomata occurred, 4 of which were with crocidolite and 4 with Canadian chrysotile. Two of the mesotheliomata occurred with only one day's exposure to asbestos. There was a positive association between asbestosis and lung tumours.}, } @article {pmid4809914, year = {1974}, author = {McDonald, JC and Becklake, MR and Gibbs, GW and McDonald, AD and Rossiter, CE}, title = {The health of chrysotile asbestos mine and mill workers of Quebec.}, journal = {Archives of environmental health}, volume = {28}, number = {2}, pages = {61-68}, doi = {10.1080/00039896.1974.10666438}, pmid = {4809914}, issn = {0003-9896}, mesh = {Adult ; Aged ; Asbestos/*toxicity ; Asbestosis/diagnostic imaging/etiology/mortality ; Bronchitis/chemically induced ; Cough/chemically induced ; Dust ; Environmental Exposure ; Female ; Gastrointestinal Neoplasms/chemically induced ; Humans ; Male ; Mesothelioma/chemically induced ; Middle Aged ; *Mining ; Mortality ; Occupational Diseases/*chemically induced ; Quebec ; Radiography ; Respiration/drug effects ; Respiratory Function Tests ; Respiratory Tract Neoplasms/chemically induced ; Smoking/complications ; }, } @article {pmid4478226, year = {1974}, author = {Anspach, M}, title = {[Extrathoracic asbestos cancer].}, journal = {Radiobiologia, radiotherapia}, volume = {15}, number = {2}, pages = {253-257}, pmid = {4478226}, issn = {0033-8184}, mesh = {Asbestosis/*complications ; Carcinoma, Bronchogenic/etiology ; Colonic Neoplasms/etiology ; Environmental Exposure ; Female ; Gastrointestinal Neoplasms/*etiology ; Humans ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Ovarian Neoplasms/*etiology ; Peritoneal Neoplasms/etiology ; Rectal Neoplasms/etiology ; Stomach Neoplasms/etiology ; }, } @article {pmid4460418, year = {1974}, author = {Sturm, W}, title = {[Pleural mesotheliomas and asbestos exposure (author's transl)].}, journal = {Zeitschrift fur Erkrankungen der Atmungsorgane}, volume = {141}, number = {1}, pages = {24-30}, pmid = {4460418}, issn = {0303-657X}, mesh = {Adult ; Aged ; Air Pollution ; Asbestos/*adverse effects ; Asbestosis/*complications ; Environmental Exposure ; Female ; Humans ; Male ; Mesothelioma/complications/*etiology ; Middle Aged ; Pleural Neoplasms/complications/*etiology ; }, } @article {pmid4439815, year = {1974}, author = {Pylev, LN}, title = {[Carcinogenic activity of chrysotile asbestos administered intrapleurally to rats].}, journal = {Voprosy onkologii}, volume = {20}, number = {4}, pages = {47-53}, pmid = {4439815}, issn = {0507-3758}, mesh = {Animals ; Asbestos/administration & dosage/*pharmacology ; Carcinogens/administration & dosage/*pharmacology ; Dust ; Female ; Lung/drug effects/pathology ; Lung Neoplasms/chemically induced/pathology ; Male ; Mesothelioma/chemically induced/pathology ; Particle Size ; Pleura/drug effects/pathology ; Pleural Neoplasms/chemically induced/pathology ; Rats ; }, } @article {pmid4129635, year = {1973}, author = {Navrátil, M and Dobiás, J}, title = {Development of pleural hyalinosis in long term studies of persons exposed to asbestos dust.}, journal = {Environmental research}, volume = {6}, number = {4}, pages = {455-472}, doi = {10.1016/0013-9351(73)90059-5}, pmid = {4129635}, issn = {0013-9351}, mesh = {Age Factors ; Aged ; *Asbestos ; Asbestosis/complications/mortality ; Carcinoma, Bronchogenic/mortality ; Dust ; Environmental Exposure ; Female ; Follow-Up Studies ; Humans ; *Hyalin ; Lung Neoplasms/mortality ; Male ; Mesothelioma/mortality ; Middle Aged ; Pleural Diseases/*chemically induced/complications/diagnostic imaging/mortality/pathology ; Radiography ; Time Factors ; }, } @article {pmid4758419, year = {1973}, author = {}, title = {Editorial: Asbestos hazard.}, journal = {British medical journal}, volume = {4}, number = {5888}, pages = {312-313}, pmid = {4758419}, issn = {0007-1447}, mesh = {Air Pollution ; Asbestosis/*epidemiology ; Environmental Exposure ; Humans ; Lung Neoplasms/chemically induced ; Mesothelioma/chemically induced ; Occupational Diseases ; Pulmonary Fibrosis/chemically induced ; United Kingdom ; }, } @article {pmid4798692, year = {1973}, author = {Gobbato, F and Ferri, R}, title = {[Epidemiologic study on pleural mesothelioma in the Trieste area].}, journal = {Lavoro umano}, volume = {25}, number = {6}, pages = {161-171}, pmid = {4798692}, issn = {0023-9127}, mesh = {Aged ; Asbestos/adverse effects ; Asbestosis/complications ; Environmental Exposure ; Female ; Humans ; Italy ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Diseases/*epidemiology/etiology ; Pleural Neoplasms/*epidemiology/etiology ; }, } @article {pmid4787992, year = {1973}, author = {Jackson, JW and Bennett, MH}, title = {Chest wall tumour following iodized talc pleurodesis.}, journal = {Thorax}, volume = {28}, number = {6}, pages = {788-793}, pmid = {4787992}, issn = {0040-6376}, mesh = {Adenocarcinoma/*chemically induced/diagnostic imaging/pathology ; Adult ; Autopsy ; Carcinoma, Squamous Cell/*chemically induced/diagnostic imaging/pathology ; Humans ; Male ; Pleural Diseases/chemically induced ; Pneumothorax/drug therapy ; Radiography ; Sclerosis/chemically induced ; Talc/*adverse effects/therapeutic use ; Thoracic Neoplasms/*chemically induced/diagnostic imaging/pathology ; Tomography ; }, abstract = {Jackson, J. W., and Bennett, M. H. (1973).Thorax, 28, 788-793. Chest wall tumour following iodized talc pleurodesis. A man of 37 had an iodized talc pleurodesis carried out for recurrent spontaneous pneumothorax. There was no history of industrial exposure to asbestos. Two years later he presented with pain in the right chest and radiographs at that time showed some localized pleural thickening at the site of the thoracoscopy cannulation for introduction of talc. A provisional diagnosis of talc granuloma, chemical abscess or tumour was made and exploratory thoracotomy revealed a tumour involving the chest wall, lung, and pleura which, on histological examination, showed adenocarcinoma of varying degrees of differentiation and in some parts also presenting a more squamoid appearance. Numerous doubly refractile talc particles were intimately associated with the tumour and fibrous tissue. Shortly after excision the patient developed evidence of systemic dissemination of the disease and died four months later. The possibility of this tumour being induced by the talc is discussed. A brief review is made of the various forms of talc used in surgery over the past 40 years and attention is drawn to the significance of the proportion of asbestos mineral which is present in talc as mined in various parts of the world. We do not consider that this is a case of mesothelioma of the pleura.}, } @article {pmid4766195, year = {1973}, author = {Ashcroft, T}, title = {Epidemiological and quantitative relationships between mesothelioma and asbestos on Tyneside.}, journal = {Journal of clinical pathology}, volume = {26}, number = {11}, pages = {832-840}, pmid = {4766195}, issn = {0021-9746}, mesh = {Adult ; Aged ; *Asbestos ; Asbestosis/complications ; Autopsy ; England ; *Environmental Exposure ; Female ; Humans ; Lung/pathology ; Male ; Mesothelioma/complications/*epidemiology/pathology ; Middle Aged ; Occupational Diseases/*epidemiology/pathology ; Occupations ; Peritoneal Neoplasms/complications/*epidemiology/pathology ; Pleural Neoplasms/complications/*epidemiology/pathology ; Time Factors ; }, abstract = {Thirty-five necropsied cases of diffuse malignant mesothelioma of pleura and six cases of mesothelioma of peritoneum are reported. Occupational histories from 40 cases showed that 32 cases (80%) were definitely exposed to asbestos; six cases (15%) were probably exposed and two (5%) had no known exposure. The mean latent interval was 34 years. Occupational histories of 56 control patients matched in pairs for age and sex with 28 of the mesothelioma cases revealed definite exposure to asbestos in 12 controls (21%), probable exposure in 11 (20%), and no evidence of exposure in 33 (59%). The difference in incidence of exposure between mesotheliomas and controls is statistically highly significant. Six-micron histological sections of lung, available in 39 mesothelioma cases, contained coated asbestos fibres in 36 cases (92%). Sixteen cases of mesothelioma showing fibres were free of asbestosis; asbestosis was slight in 14 cases, moderately severe in five cases, and severe in one case. The incidence of asbestos bodies in sections from mesothelioma cases was significantly higher than in a previously reported series of routine necropsies examined by lung smear. Counts of coated and uncoated asbestos fibres were performed on samples of lung tissue from 33 mesothelioma cases. No fibres were identified in one case and only occasional coated fibres in a second case. The remainder gave counts ranging from 154 thousand to 684 million fibres per gram dry weight. Uncoated fibres were invariably present and usually comprised 50 to 80% of the count. No relationship was found between total fibre count and the latent period of the mesothelioma. Fibre counts were also performed on lung samples from 18 smear-positive and 30 smear-negative routine necropsies. Cases with numerous coated fibres in the smear gave total fibre counts similar to those of mesothelioma cases without asbestosis. Routine cases with only one fibre in the smear usually yielded only occasional fibres on analysis. Coated and uncoated fibres were found in 13 out of 30 smear-negative cases, indicating a true incidence of 56% of exposure to asbestos in the whole necropsy series. When compared with the mesothelioma series the difference in incidence of fibres remains statistically significant. The data suggest that, on Tyneside, exposure to asbestos sufficient to cause an appreciable risk of developing mesothelioma has usually occurred through occupational exposure rather than by general environmental pollution by asbestos.}, } @article {pmid4750338, year = {1973}, author = {Borow, M and Conston, A and Livornese, L and Schalet, N}, title = {Mesothelioma following exposure to asbestos: a review of 72 cases.}, journal = {Chest}, volume = {64}, number = {5}, pages = {641-646}, doi = {10.1378/chest.64.5.641}, pmid = {4750338}, issn = {0012-3692}, mesh = {Adult ; Antineoplastic Agents/therapeutic use ; *Asbestos ; Asbestosis/complications ; Environmental Exposure ; Female ; Humans ; Lung Neoplasms/diagnosis/diagnostic imaging/drug therapy/*etiology/mortality/radiotherapy ; Male ; Mesothelioma/diagnosis/diagnostic imaging/drug therapy/*etiology/mortality/radiotherapy ; Middle Aged ; Occupational Medicine ; Peritoneal Neoplasms/etiology ; Pleural Neoplasms/etiology ; Radiography ; Time Factors ; }, } @article {pmid4584933, year = {1973}, author = {Eckardt, RE}, title = {Recent developments in industrial carcinogens.}, journal = {Journal of occupational medicine. : official publication of the Industrial Medical Association}, volume = {15}, number = {11}, pages = {904-907}, pmid = {4584933}, issn = {0096-1736}, mesh = {Amines ; Animals ; Arsenic Poisoning ; Asbestos/poisoning ; Benzene/poisoning ; *Carcinogens ; Coal/poisoning ; Humans ; Leukemia/chemically induced ; Lung Neoplasms/chemically induced ; Mesothelioma/chemically induced ; Methyl Chloride ; Methyl Ethers ; Naphthalenes ; Neoplasms/*chemically induced ; Neoplasms, Radiation-Induced ; Nose Neoplasms/etiology ; Occupational Diseases/*chemically induced ; Peritoneal Neoplasms/chemically induced ; Radon/poisoning ; Schistosomiasis/complications ; Skin Neoplasms/chemically induced ; Smoking/complications ; Sulfur Dioxide/poisoning ; Uranium/poisoning ; Urinary Bladder Neoplasms/chemically induced/etiology ; }, } @article {pmid4355264, year = {1973}, author = {Gross, P and Harley, RA}, title = {Asbestos-induced intrathoracic tissue reactions.}, journal = {Archives of pathology}, volume = {96}, number = {4}, pages = {245-250}, pmid = {4355264}, issn = {0363-0153}, mesh = {Animals ; *Asbestos ; Collagen ; Cricetinae ; *Dust ; Granulation Tissue/pathology ; Heating ; Hyperplasia/pathology ; Lung Neoplasms/*etiology/pathology ; Male ; Mesothelioma/etiology/pathology ; Neoplasms, Experimental/etiology ; Neoplasms, Muscle Tissue/etiology/pathology ; Pleural Neoplasms/etiology/pathology ; Rats ; Rhabdomyosarcoma/etiology ; Sarcoma/etiology/pathology ; Thoracic Neoplasms/*etiology/pathology ; Time Factors ; }, } @article {pmid4131846, year = {1973}, author = {Parkes, WR}, title = {Asbestos-related disorders.}, journal = {British journal of diseases of the chest}, volume = {67}, number = {4}, pages = {261-300}, doi = {10.1016/s0007-0971(73)80001-4}, pmid = {4131846}, issn = {0007-0971}, mesh = {Asbestos ; Asbestosis/*complications/diagnostic imaging/pathology/prevention & control ; Calcinosis/complications ; Environmental Exposure ; Female ; Humans ; Hyalin ; Lung/pathology ; Lung Neoplasms/complications/pathology ; Male ; Mesothelioma/complications ; Neoplasm Metastasis ; Occupational Diseases ; Pleural Diseases/pathology ; Pleural Effusion/etiology ; Pleural Neoplasms/etiology ; Prognosis ; Pulmonary Fibrosis/etiology ; Radiography ; Respiratory Function Tests ; Sputum ; }, } @article {pmid4745080, year = {1973}, author = {Engelbrecht, FM and Burger, BF}, title = {Biological effect of asbestos dust on the peritoneal viscera of rats.}, journal = {South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde}, volume = {47}, number = {38}, pages = {1746-1750}, pmid = {4745080}, issn = {0256-9574}, mesh = {Animals ; Asbestos/*toxicity ; Female ; Injections, Intraperitoneal ; Mesothelioma/*chemically induced/pathology ; Neoplasms, Experimental/chemically induced/pathology ; Peritoneal Neoplasms/*chemically induced/pathology ; Peritoneum/pathology ; Rats ; }, } @article {pmid4742473, year = {1973}, author = {McDonald, AD and McDonald, JC}, title = {Epidemiologic surveillance of mesothelioma in Canada.}, journal = {Canadian Medical Association journal}, volume = {109}, number = {5}, pages = {359-362}, pmid = {4742473}, issn = {0008-4409}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Autopsy ; Biopsy ; Canada ; Epidemiologic Methods ; Female ; Humans ; Male ; Mesothelioma/chemically induced/*epidemiology/etiology/mortality/pathology ; Middle Aged ; Occupational Diseases/epidemiology ; Peritoneal Neoplasms/chemically induced/*epidemiology/etiology/mortality/pathology ; Pleural Neoplasms/chemically induced/*epidemiology/etiology/mortality/pathology ; Smoking/complications ; }, abstract = {The number of fatal malignant mesotheliomas was ascertained for the period 1960-70 by contacting all pathologists in Canada. The annual incidence was steady between 1966 and 1970 at 1.4 per million population. Of 71 cases registered in 1968-70 and not previously reported, 66% were pleural, 24% peritoneal and the remainder in both sites; 45% of tumours were in women. The diagnosis of mesothelioma was approved by the Canadian Mesothelioma Panel in 59%. Sixty-nine cases were successfully investigated epidemiologically. A history of definite or probable occupational asbestos exposure was found in 30% of male cases compared with 11% of controls, but in none of the female cases or controls. However, among cases, four women and one man had had domestic exposure to dusty clothing of an asbestos worker. Most of the excess occupational exposure was in the manufacture of asbestos products or insulation and little in mining or milling. No case other than those occupationally or domestically exposed had lived within 20 miles of asbestos mines or mills.}, } @article {pmid4802402, year = {1973}, author = {Newhouse, ML}, title = {Asbestos in the work place and the community.}, journal = {The Annals of occupational hygiene}, volume = {16}, number = {2}, pages = {97-107}, doi = {10.1093/annhyg/16.2.97}, pmid = {4802402}, issn = {0003-4878}, mesh = {Asbestos/*adverse effects/analysis ; Dose-Response Relationship, Drug ; *Environmental Exposure ; Female ; Follow-Up Studies ; Humans ; Male ; Mesothelioma/chemically induced ; Mortality ; Neoplasms/chemically induced ; Occupational Diseases/*chemically induced ; }, } @article {pmid4354178, year = {1973}, author = {Wagner, JC and Berry, G and Timbrell, V}, title = {Mesotheliomata in rats after inoculation with asbestos and other materials.}, journal = {British journal of cancer}, volume = {28}, number = {2}, pages = {173-185}, pmid = {4354178}, issn = {0007-0920}, mesh = {Aluminum/toxicity ; Animals ; Asbestos/*toxicity ; Barium Sulfate/toxicity ; Glass/toxicity ; Mesothelioma/*chemically induced/mortality ; Methods ; Microscopy, Electron ; Neoplasms, Experimental/chemically induced ; Rats ; Silicon Dioxide/toxicity ; Time Factors ; }, abstract = {Four experiments in which SPF Wistar rats were inoculated intrapleurally with asbestos or other materials are described. Mesotheliomata were observed in a considerable proportion of animals with all the samples of asbestos used and with a sample of brucite. A few were produced with synthetic aluminium silicate fibres and single ones with barium sulphate, glass powder and aluminium oxide. The risk of developing a mesothelioma at a given time after injection was approximately proportional to the dose. Of the UICC standard reference samples, crocidolite was the most carcinogenic and removal of the oils by benzene extraction did not alter the carcinogenicity of these samples. Chemical properties also seem unlikely to be the main factor producing mesotheliomata but the results support the hypothesis that the finer fibres are the more carcinogenic, and this is additional to the known aerodynamic advantage which the finer fibres have in penetrating to the periphery of the lung.}, } @article {pmid4779700, year = {1973}, author = {Hägerstrand, I and Seifert, B}, title = {Asbestos bodies and pleural plaques in human lungs at necropsy.}, journal = {Acta pathologica et microbiologica Scandinavica. Section A, Pathology}, volume = {81}, number = {4}, pages = {457-460}, doi = {10.1111/j.1699-0463.1973.tb00492.x}, pmid = {4779700}, issn = {0365-4184}, mesh = {Adult ; Aged ; Asbestos/*analysis ; Asbestosis/epidemiology/*pathology ; Autopsy ; Female ; Functional Laterality ; Humans ; Lung/*pathology ; Lung Neoplasms/pathology ; Male ; Mesothelioma/pathology ; Middle Aged ; Occupations ; Pleural Diseases/epidemiology/*pathology ; Sex Factors ; Sweden ; }, } @article {pmid4779697, year = {1973}, author = {Pooley, FD}, title = {Asbestos fibre in the lung and mesothelioma. A re-examination of the Malmö material.}, journal = {Acta pathologica et microbiologica Scandinavica. Section A, Pathology}, volume = {81}, number = {4}, pages = {390-400}, doi = {10.1111/j.1699-0463.1973.tb00485.x}, pmid = {4779697}, issn = {0365-4184}, mesh = {Asbestos/*analysis ; Asbestosis/complications/*pathology ; Autopsy ; Humans ; Lung/*pathology ; Mesothelioma/complications/*pathology ; Microscopy, Electron, Scanning ; Peritoneal Neoplasms/complications/*pathology ; Pleural Neoplasms/complications/*pathology ; }, } @article {pmid4713751, year = {1973}, author = {Bianchi, C and Di Bonito, L and Grandi, G and Furlan, L}, title = {[Occupational exposure to asbestos in 20 cases of diffuse mesothelioma of the pleura].}, journal = {Minerva medica}, volume = {64}, number = {32}, pages = {1724-1727}, pmid = {4713751}, issn = {0026-4806}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Autopsy ; Environmental Exposure ; Environmental Pollution ; Humans ; Male ; Mesothelioma/*chemically induced/pathology ; Middle Aged ; Occupational Diseases/*chemically induced/pathology ; Pleural Neoplasms/*chemically induced/pathology ; Seasons ; }, } @article {pmid4729288, year = {1973}, author = {Smith, WE}, title = {Asbestos, talc and nitrites in relation to gastric cancer.}, journal = {American Industrial Hygiene Association journal}, volume = {34}, number = {5}, pages = {227-228}, doi = {10.1080/0002889738506838}, pmid = {4729288}, issn = {0002-8894}, mesh = {Animals ; Asbestos/*toxicity ; Chile ; Cricetinae ; Diet ; Injections ; Japan ; Mesothelioma/chemically induced ; Nitrites/*toxicity ; Pleural Neoplasms/chemically induced ; Stomach Neoplasms/*chemically induced/epidemiology ; Talc/*toxicity ; }, } @article {pmid4121234, year = {1973}, author = {}, title = {Asbestos leads to lung cancer leads to mesothelioma.}, journal = {Lancet (London, England)}, volume = {1}, number = {7807}, pages = {815-816}, pmid = {4121234}, issn = {0140-6736}, mesh = {Asbestos/*adverse effects ; Asbestosis/complications/etiology ; Environmental Exposure ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Occupational Diseases ; Time Factors ; }, } @article {pmid4121226, year = {1973}, author = {Maroudas, NG and O'Neill, CH and Stanton, MF}, title = {Fibroblast anchorage in carcinogenesis by fibres.}, journal = {Lancet (London, England)}, volume = {1}, number = {7807}, pages = {807-809}, doi = {10.1016/s0140-6736(73)90604-1}, pmid = {4121226}, issn = {0140-6736}, mesh = {Animals ; Asbestos/*adverse effects ; Cells, Cultured ; *Fibroblasts ; Foreign Bodies/complications ; Humans ; Hyperplasia/etiology ; Lung Neoplasms/etiology ; Mesothelioma/*etiology ; Methods ; Particle Size ; Peritoneal Neoplasms/etiology ; Phagocytosis ; Pleural Neoplasms/etiology ; Rats ; }, } @article {pmid4775396, year = {1973}, author = {}, title = {Biological effects of asbestos. Report of the Advisory Committee on Asbestos Cancers to the director of the international agency for research on cancer.}, journal = {The Annals of occupational hygiene}, volume = {16}, number = {1}, pages = {9-17}, pmid = {4775396}, issn = {0003-4878}, mesh = {*Asbestos ; Asbestosis/pathology ; Humans ; International Cooperation ; Lung Neoplasms/pathology ; Mesothelioma/pathology ; Neoplasms/*chemically induced ; Research ; }, } @article {pmid4706052, year = {1973}, author = {McDonald, AD and Magner, D and Eyssen, G}, title = {Primary malignant mesothelial tumors in Canada, 1960-1968. A pathologic review by the Mesothelioma Panel of the Canadian Tumor Reference Centre.}, journal = {Cancer}, volume = {31}, number = {4}, pages = {869-876}, doi = {10.1002/1097-0142(197304)31:4<869::aid-cncr2820310416>3.0.co;2-s}, pmid = {4706052}, issn = {0008-543X}, mesh = {Asbestos ; Canada ; Female ; Humans ; Male ; Mesothelioma/chemically induced/*epidemiology/pathology ; Microscopy, Electron ; Occupational Diseases/chemically induced ; Peritoneal Neoplasms/chemically induced/*epidemiology/pathology ; Pleura/pathology ; Pleural Neoplasms/chemically induced/*epidemiology/pathology ; Registries ; }, } @article {pmid4703088, year = {1973}, author = {Hunter, B and Thomson, C}, title = {Evaluation of the tumorigenic potential of vermiculite by intrapleural injection in rats.}, journal = {British journal of industrial medicine}, volume = {30}, number = {2}, pages = {167-173}, pmid = {4703088}, issn = {0007-1072}, mesh = {Adenocarcinoma/pathology ; Adenoma/pathology ; Animals ; Asbestos ; Body Weight ; *Carcinogens ; Chemical and Drug Induced Liver Injury ; Female ; Granuloma/pathology ; Injections ; Kidney Diseases/chemically induced ; Lung Diseases/chemically induced/pathology ; Lung Neoplasms/pathology ; Mesothelioma/chemically induced/pathology ; Minerals/administration & dosage/*toxicity ; Pleura ; Rats ; Sarcoma/pathology ; }, abstract = {Hunter, B., and Thomson, C. (1973).British Journal of Industrial Medicine,30, 167-173. Evaluation of the tumorigenic potential of vermiculite by intrapleural injection in rats. Vermiculite, the geological name for a group of hydrated laminar minerals, has industrial application in areas previously restricted to the use of asbestos. In this assessment of its tumorigenicity, Rhodesian chrysotile asbestos or vermiculite was injected into the pleural cavity of rats. Mesotheliomata developed in 48% of the rats treated with asbestos. No tumours occurred which were associated with the vermiculite injections.}, } @article {pmid4577339, year = {1973}, author = {Gilson, JC}, title = {Asbestos cancer: past and future hazards.}, journal = {Proceedings of the Royal Society of Medicine}, volume = {66}, number = {4}, pages = {395-403}, pmid = {4577339}, issn = {0035-9157}, mesh = {Asbestos/*adverse effects/history ; Asbestosis/complications/diagnostic imaging ; Dust ; Female ; History, 19th Century ; History, 20th Century ; Humans ; Lung Neoplasms/chemically induced ; Male ; Mesothelioma/chemically induced/epidemiology ; Neoplasms/*chemically induced/prevention & control ; Occupational Diseases ; Occupational Medicine ; Quebec ; Radiography ; Refuse Disposal ; Sex Factors ; Smoking/complications ; United Kingdom ; United States ; }, } @article {pmid4574040, year = {1973}, author = {}, title = {Report of the Advisory Committee on Asbestos Cancers to the Director of the International Agency for Research on Cancer.}, journal = {British journal of industrial medicine}, volume = {30}, number = {2}, pages = {180-186}, pmid = {4574040}, issn = {0007-1072}, mesh = {Animals ; Asbestos/*adverse effects/toxicity ; Asbestosis/pathology ; Clinical Trials as Topic ; Humans ; International Cooperation ; Lung Neoplasms/chemically induced/pathology ; Mesothelioma/chemically induced/pathology ; Neoplasms/*chemically induced/epidemiology/pathology ; Research ; }, abstract = {In 1964 the Geographical Pathology Committee of the International Union against Cancer (UICC) set up a working group on asbestos and cancer and later issued a Report and Recommendations (1965). A further meeting was held at the International Agency for Research on Cancer (IARC), Lyon, France, on 5 and 6 October 1972. This was organized jointly with the Medical Research Council Pneumoconiosis Research Unit. The report and recommendations given here will also be published by IARC in 1973, together with the complete proceedings of the meeting. The Committee consisted of three panels—Epidemiology, Pathology, and Physics and Chemistry.}, } @article {pmid4689512, year = {1973}, author = {Shin, ML and Firminger, HI}, title = {Acute and chronic effects of intraperitoneal injection of two types of asbestos in rats with a study of the histopathogenesis and ultrastructure of resulting mesotheliomas.}, journal = {The American journal of pathology}, volume = {70}, number = {3}, pages = {291-313}, pmid = {4689512}, issn = {0002-9440}, mesh = {Animals ; Asbestos/*toxicity ; Blood Protein Electrophoresis ; Granuloma/*chemically induced/pathology ; Histocytochemistry ; Hyaluronic Acid/biosynthesis ; Injections, Intraperitoneal ; Male ; Mesothelioma/*chemically induced/metabolism/pathology ; Microscopy, Electron ; Neoplasm Metastasis ; Neoplasms, Experimental ; Peritoneal Neoplasms/*chemically induced/classification/pathology ; Peritoneum/pathology ; Peritonitis/*chemically induced/pathology ; Rats ; Time Factors ; }, abstract = {Malignant mesotheliomas were induced in the rat peritoneum by a single injection of chrysotile or crocidolite asbestos fibers. The immediate toxicity of the fibers was noted in both groups of animals, producing approximately 40% mortality, within 8 days after the injection associated with acute peritonities. Tissue reactions to these two types of asbestos were significantly different. Crocidolite fibers were easily seen by light microscopy, in the tissue sections throughout the period of study, and they produced foreign-body giant cell granulomas. However, giant cells were not seen in chrysotile granulomas, and the asbestos fibers were only seen by electron microscopic study. They appeared to be coated by a protein-like substance. During earlier stages of tumorigenesis, the epithelioid and/or mixed cell type mesotheliomas seemed to have no specific relationship to granulomas, but pure spindle cell tumors were seen to develop in close relationship to granulomas, and they appear to be fibrosarcomas. Electron microscopic and histochemical methods were used to define the morphologic characteristics of the tumor cells. The formation of hyaluronic acid was found in cells of the epithelioid type, contrasted with extracellular accumulation in the spindle cell tumors.}, } @article {pmid4686513, year = {1973}, author = {Nizze, H}, title = {Exposure to asbestos and the genesis of pleural plaques and neoplasia.}, journal = {Archives of pathology}, volume = {95}, number = {3}, pages = {213-214}, pmid = {4686513}, issn = {0363-0153}, mesh = {Asbestosis/*complications ; Carcinoma, Bronchogenic/etiology ; Gastrointestinal Neoplasms/etiology ; Humans ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Neoplasms/*etiology ; Pleural Diseases/*etiology ; Pleural Neoplasms/etiology ; }, } @article {pmid4573359, year = {1973}, author = {Ashcroft, T and Heppleston, AG}, title = {The optical and electron microscopic determination of pulmonary asbestos fibre concentration and its relation to the human pathological reaction.}, journal = {Journal of clinical pathology}, volume = {26}, number = {3}, pages = {224-234}, pmid = {4573359}, issn = {0021-9746}, mesh = {Asbestos/*analysis/isolation & purification ; Asbestosis/complications/*pathology ; Centrifugation ; Humans ; Inflammation ; Lung/*analysis/pathology ; Lung Neoplasms/classification ; Mesothelioma/complications ; Methods ; Microscopy, Electron ; Microscopy, Phase-Contrast ; Pulmonary Fibrosis/pathology ; }, abstract = {The quantitative extraction of asbestos fibres from asbestotic lung by alkali digestion has been refined by maceration of the tissue without prior drying, the minimum use of centrifugation, and the adoption of phase contrast microscopy. Preliminary experiments suggested that, using this technique, asbestos fibre counts were accurate to within at least +/- 20% and in most instances to within +/- 10%. The method was used to assess asbestos concentrations in lung tissue showing various degrees and forms of fibrosis. The results, as determined by light microscopy, indicated that uncoated fibres generally outnumbered coated fibres. In mild and moderate asbestosis there was a progressive increase in concentration of asbestos fibres, both coated and uncoated, with increasing severity of fibrosis, whereas in severe asbestosis no correlation existed between the fibre concentration and the form or the extent of the pathological reaction. It is suggested that the severe fibrosis results from the supervention of non-specific inflammatory processes. Asbestos fibre diameter distributions, gauged by electron microscopy, were fairly constant irrespective of the degree of fibrosis. Optically visible fibres constituted between 12 and 30% of the total, so that an optical count may be said to give an approximate indication of the total asbestos concentration and, so far as asbestosis is concerned, may well serve for comparative purposes. The relation between asbestos and neoplasia will, however, require identification and quantitation of particular types of the mineral by microanalytical techniques.}, } @article {pmid4571333, year = {1973}, author = {Kleinfeld, M}, title = {Biologic response to kind and amount of asbestos.}, journal = {Journal of occupational medicine. : official publication of the Industrial Medical Association}, volume = {15}, number = {3}, pages = {296-300}, pmid = {4571333}, issn = {0096-1736}, mesh = {Animals ; Asbestos/*adverse effects/toxicity ; Asbestosis/etiology ; Calcinosis/chemically induced ; Carcinoma, Bronchogenic/chemically induced ; Dust ; Environmental Exposure ; Gastrointestinal Neoplasms/mortality ; Humans ; Lung Neoplasms/chemically induced/mortality ; Mesothelioma/chemically induced ; Occupational Diseases/chemically induced ; Peritoneal Neoplasms/chemically induced/mortality ; Pleural Neoplasms/chemically induced/mortality ; Pulmonary Fibrosis/chemically induced ; Respiratory Tract Diseases/mortality ; South Africa ; Thoracic Neoplasms/chemically induced ; Trace Elements/adverse effects ; United States ; }, } @article {pmid4684243, year = {1973}, author = {Webster, I}, title = {Asbestos and malignancy.}, journal = {South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde}, volume = {47}, number = {5}, pages = {165-171}, pmid = {4684243}, issn = {0256-9574}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Asbestosis/pathology ; Environmental Exposure ; Humans ; Male ; Mesothelioma/*chemically induced/epidemiology/pathology ; Middle Aged ; Minerals ; Mining ; Occupational Diseases/chemically induced/epidemiology ; Pleura/pathology ; Pleural Neoplasms/*chemically induced/epidemiology/pathology ; Pulmonary Alveoli/pathology ; South Africa ; }, } @article {pmid4684241, year = {1973}, author = {}, title = {The dangers of asbestos.}, journal = {South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde}, volume = {47}, number = {5}, pages = {161-162}, pmid = {4684241}, issn = {0256-9574}, mesh = {Asbestos/*adverse effects ; Environmental Pollution/prevention & control ; Humans ; Mesothelioma/*chemically induced ; Pleural Neoplasms/*chemically induced ; }, } @article {pmid4685429, year = {1973}, author = {Blejer, HP and Arlon, R}, title = {Talc: a possible occupational and environmental carcinogen.}, journal = {Journal of occupational medicine. : official publication of the Industrial Medical Association}, volume = {15}, number = {2}, pages = {92-97}, pmid = {4685429}, issn = {0096-1736}, mesh = {Asbestos/adverse effects/analysis ; Asbestosis/chemically induced ; *Carcinogens ; Carcinoma, Bronchogenic/chemically induced ; Environmental Exposure ; *Environmental Health ; Food Contamination/analysis ; Food-Processing Industry ; Gastrointestinal Neoplasms/chemically induced ; Humans ; Lung Neoplasms/chemically induced ; Maximum Allowable Concentration ; Mesothelioma/chemically induced ; Occupational Diseases/*chemically induced ; Occupational Medicine ; Oryza/analysis ; Peritoneal Neoplasms/chemically induced ; Pleural Neoplasms/chemically induced ; Pulmonary Fibrosis/chemically induced ; Talc/*adverse effects/analysis ; United States ; }, } @article {pmid4690352, year = {1973}, author = {}, title = {Asbestos as an industrial health hazard.}, journal = {The Medical journal of Australia}, volume = {1}, number = {3}, pages = {92}, doi = {10.5694/j.1326-5377.1973.tb119649.x}, pmid = {4690352}, issn = {0025-729X}, mesh = {Asbestos/*adverse effects ; Humans ; Lung Neoplasms/*chemically induced ; Mesothelioma/*chemically induced ; Occupational Diseases/*chemically induced ; Peritoneal Neoplasms/*chemically induced ; Pleural Neoplasms/*chemically induced ; }, } @article {pmid4763405, year = {1973}, author = {Zeedijk, HB}, title = {[Electron microscopic studies of asbestos bodies and asbestos fibers in the lung of a patient with mesothelioma].}, journal = {Mikrochimica acta}, volume = {}, number = {6}, pages = {977-984}, pmid = {4763405}, issn = {0026-3672}, mesh = {Asbestos/*analysis ; Humans ; Lung Neoplasms/*pathology ; Mesothelioma/*pathology ; Microscopy, Electron ; }, } @article {pmid4685301, year = {1973}, author = {Knox, EG}, title = {Computer simulation of industrial hazards.}, journal = {British journal of industrial medicine}, volume = {30}, number = {1}, pages = {54-63}, pmid = {4685301}, issn = {0007-1072}, mesh = {Adult ; Age Factors ; Aged ; Asbestosis/mortality ; *Computers ; Dose-Response Relationship, Drug ; Employment ; Environmental Exposure ; Female ; Humans ; Intestinal Neoplasms/mortality ; Life Expectancy ; Lung Neoplasms/mortality ; Male ; Mesothelioma/mortality ; Middle Aged ; *Models, Biological ; *Occupational Diseases/epidemiology/mortality ; Personnel Management ; Retirement ; Time Factors ; }, abstract = {Knox, E. G. (1973).Brit. J. industr. Med.,30, 54-63. Computer simulation of industrial hazards. A computer simulation system for a range of industrial hazards provided for model experiments which manipulated (a) the sub-structure of an exposed population in terms of age-distributions and levels of exposure, (b) the nature of the dose/response relationship, (c) the latent interval and its variability, (d) normal life-table expectations, and (e) employment turnover rates. The development of the system led to clarification of terms and concepts with ambiguous current usages, notably in relation to latency. Distinction is made between the notions of `biological' and `observable' latent intervals. Hypothetical exercises with the model tested its technical validity and at the same time demonstrated in quantitative terms the relationships between `biological' and `observable' latent intervals, employment turnover rates, total mortalities, and the distribution of illnesses and death between those currently employed in the exposing industry, those employed elsewhere, and those retired. Prospects of success for personnel engineering techniques, which manipulate age-distributions of exposed work people in relation to diseases with long latent intervals, were examined. Published asbestos cancer data were used as a basis for specific model fitting and resulted in a numerical formulation of the exposure/response relationships. Severe exposure results in an increment of risk of death of about 0·02 unit per person per annum for those exposed for around six years, but with higher rates for shorter exposures and lower rates for longer ones. The mean biological latent interval was about 25 years with a coefficient of variation of about 25%. These suppositions explained a range of published data comprehensively and at the same time predicted that (a) persons exposed at severe levels for a working lifetime of 50 years have a 40% risk of dying from asbestos cancer, and (b) industrial populations with moderate to high turnover rates effect a form of extended dose sharing, and non-linearity of the exposure/response relationship results in substantially more deaths than would be the case if the turnover rate were lower.}, } @article {pmid4582363, year = {1973}, author = {Scheuer, E and Huth, F and Pott, F}, title = {[Studies of morphology of rat tumors induced by intraperitoneal injection of asbestos dusts].}, journal = {Archiv fur Geschwulstforschung}, volume = {41}, number = {2}, pages = {120-136}, pmid = {4582363}, issn = {0003-911X}, mesh = {Adenocarcinoma/chemically induced/pathology ; Animals ; Asbestos ; Benzopyrenes ; Dust ; Female ; Fibrosarcoma/chemically induced/pathology ; Injections, Intraperitoneal ; Lymphoma, Large B-Cell, Diffuse/chemically induced/pathology ; Mesothelioma/chemically induced/pathology ; Neoplasms, Experimental/chemically induced/*pathology ; Rats ; Sarcoma, Experimental/chemically induced/pathology ; Time Factors ; }, } @article {pmid4651614, year = {1972}, author = {Sluis-Cremer, GK and Webster, I}, title = {Acute pleurisy in asbestos exposed persons.}, journal = {Environmental research}, volume = {5}, number = {4}, pages = {380-392}, doi = {10.1016/0013-9351(72)90040-0}, pmid = {4651614}, issn = {0013-9351}, mesh = {Acute Disease ; Adult ; Asbestos ; Asbestosis/*complications/pathology ; Biopsy, Needle ; Environmental Exposure ; Humans ; Male ; Mesothelioma/complications/pathology ; Middle Aged ; Pleural Effusion/etiology ; Pleural Neoplasms/complications/pathology ; Pleurisy/*etiology/pathology ; }, } @article {pmid4646196, year = {1972}, author = {Botham, SK and Holt, PF}, title = {The effects of inhaled crocidolites from Transvaal and North-west Cape mines on the lungs of rats and guinea-pigs.}, journal = {British journal of experimental pathology}, volume = {53}, number = {6}, pages = {612-620}, pmid = {4646196}, issn = {0007-1021}, mesh = {Animals ; Asbestos/administration & dosage/*toxicity ; Asbestosis/*pathology ; Bronchi/pathology ; Collagen ; Disease Models, Animal ; Dust ; Guinea Pigs ; Lung/*pathology ; Lung Neoplasms/chemically induced ; Male ; Mesothelioma/chemically induced ; Microscopy, Electron ; Rats ; South Africa ; }, abstract = {A group of guinea-pigs and another of rats were successively placed for 400 hours in an atmosphere containing a high concentration of North-west Cape (NWC) crocidolite fibres. A further group of guinea-pigs inhaled Transvaal (TVL) crocidolite for an equal time. Guinea-pigs that inhaled NWC crocidolite were substantially outlived by animals of the other 2 groups, of which the longest survivors were 2 guinea-pigs. No mesotheliomata were found but in all the lungs cellular proliferation of the septa caused a reduction in alveolar space. Giant cells were common and asbestos bodies developed in guinea-pigs, but in rats only a very few, atypical asbestos bodies were seen, and giant cells were rare. All lungs contained uncoated fibres, long fibres (occasionally exceeding 50 μm) being seen in subpleural regions in older animals and in peribronchiolar accumulations. NWC fibres reached the muscular coats of larger bronchioles of guinea-pigs sooner than TVL crocidolite. Proliferation of bronchiolar epithelium was produced in guinea-pigs and 2 rats by NWC crocidolite, but not by TVL crocidolite. Guinea-pigs dying over 3 months and rats over 18 months after inhalation of NWC crocidolite had several small emphysematous regions at the lung periphery, but only one small area was seen in each of the last 2 guinea-pigs that inhaled TVL fibres. Thus, NWC crocidolite produced greater disruption of the respiratory surfaces. Severe lung fibrosis was not seen, although fine collagen strands were found in interalveolar septa of animals dying at over 5 months after dusting began. Dense subpleural areas of collagen produced by TVL crocidolite were, however, found in the 4 oldest guinea-pigs. Inhalation of these 2 crocidolites results in different pathological responses, although no difference in distribution in the lung were found to explain differences in survival time, bronchiolar epithelial proliferation or subpleural collagen formation.}, } @article {pmid4264451, year = {1972}, author = {Barnes, R}, title = {Asbestos and malignant disease.}, journal = {The Medical journal of Australia}, volume = {2}, number = {20}, pages = {1107-1112}, doi = {10.5694/j.1326-5377.1972.tb103753.x}, pmid = {4264451}, issn = {0025-729X}, mesh = {Adult ; Asbestos/adverse effects ; Asbestosis/complications ; Carcinoma, Bronchogenic/*chemically induced/diagnostic imaging ; Humans ; Lung Neoplasms/*chemically induced/diagnostic imaging ; Male ; Mesothelioma/*chemically induced/diagnostic imaging ; Middle Aged ; Occupational Diseases/*chemically induced ; Pleural Neoplasms/*chemically induced/diagnostic imaging ; Radiography ; Smoking/complications ; Workers' Compensation ; }, } @article {pmid5083060, year = {1972}, author = {Grundy, GW and Miller, RW}, title = {Malignant mesothelioma in childhood. Report of 13 cases.}, journal = {Cancer}, volume = {30}, number = {5}, pages = {1216-1218}, doi = {10.1002/1097-0142(197211)30:5<1216::aid-cncr2820300511>3.0.co;2-5}, pmid = {5083060}, issn = {0008-543X}, mesh = {Adolescent ; Asbestos ; Child ; Child, Preschool ; Environmental Exposure ; Female ; Humans ; Male ; Mesothelioma/etiology/*mortality ; Peritoneal Neoplasms/etiology/mortality ; Pleural Neoplasms/etiology/*mortality ; }, } @article {pmid4636663, year = {1972}, author = {Rubino, GF and Scansetti, G and Donna, A and Palestro, G}, title = {Epidemiology of pleural mesothelioma in North-western Italy (Piedmont).}, journal = {British journal of industrial medicine}, volume = {29}, number = {4}, pages = {436-442}, pmid = {4636663}, issn = {0007-1072}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Asbestosis/epidemiology ; Female ; Humans ; Italy ; Male ; Mesothelioma/*epidemiology/pathology ; Middle Aged ; Occupational Diseases/*epidemiology ; Pleural Neoplasms/*epidemiology/pathology ; }, abstract = {Rubino, G. F., Scansetti, G., Donna, A., and Palestro, G. (1972).Brit. J. industr. Med.,29, 436-442. Epidemiology of pleural mesothelioma in North-western Italy (Piedmont). Fifty-four cases of mesothelioma of the pleura admitted to the Chest Surgery Centre or to the Department of Medicine of the University of Turin from 1960 to 1970 are reported. Thoracotomy was performed in 22. In the other 32 the diagnosis was based on the clinical, radiographic, and cytological findings and on the results of biopsy. In 50 cases (18 women and 32 men), the majority of whom had always or mostly lived in Piedmont, it was possible to ascertain the family history, previous residence, and occupation, mainly with the aid of information given by the patient's relatives. A similar investigation was made by the same interviewers into 50 other patients of the same sex and age admitted to the same institutions, using an identical technique. In the group with mesothelioma (only two of whom survived more than two years after the diagnosis had been made) occupational exposure to asbestos was demonstrated unequivocally in five men. Three other patients, including one woman, had lived with persons employed in the asbestos industry (16%). Exposure for occupational reasons seemed very likely in another patient, who had been a fireman in the Turin Arsenal for 40 years. One man in the control group had worked for two years in a cement-asbestos manufacturing company (2%). A re-appraisal of the histological sections and examination of new preparations made in the 22 cases operated on was done in the Department of Pathological Anatomy of the University of Turin, also with the purpose of confirming the diagnosis. This re-appraisal revealed the presence of asbestos bodies in the mesothelioma in one case, a woman who had never been exposed to asbestos for occupational or domestic reasons but who had always lived in one of the two regions of the Province of Turin with the highest number of asbestos industries.}, } @article {pmid4506886, year = {1972}, author = {Adelman, H and Berkson, P and Sackler, JP}, title = {Partial intestinal obstruction due to peritoneal mesothelioma in chronic asbestos exposure.}, journal = {New York state journal of medicine}, volume = {72}, number = {18}, pages = {2332-2334}, pmid = {4506886}, issn = {0028-7628}, mesh = {Asbestosis/*complications ; Environmental Exposure ; Humans ; Intestinal Obstruction/*etiology ; Male ; Mesothelioma/*complications/etiology ; Middle Aged ; Occupational Diseases/*complications ; Peritoneal Neoplasms/*complications/etiology ; }, } @article {pmid5050439, year = {1972}, author = {Magner, D and McDonald, AD}, title = {Malignant mesothelial tumors - histologic type and asbestos exposure.}, journal = {The New England journal of medicine}, volume = {287}, number = {11}, pages = {570-571}, pmid = {5050439}, issn = {0028-4793}, mesh = {Asbestos/*adverse effects ; Asbestosis/complications ; Environmental Exposure ; Female ; Humans ; Male ; Mesothelioma/chemically induced/classification/*pathology ; Occupational Diseases/pathology ; Peritoneal Neoplasms/classification/etiology/*pathology ; Pleural Neoplasms/classification/etiology/pathology ; }, } @article {pmid4115357, year = {1972}, author = {Berry, G and Newhouse, ML and Turok, M}, title = {Combined effect of asbestos exposure and smoking on mortality from lung cancer in factory workers.}, journal = {Lancet (London, England)}, volume = {2}, number = {7775}, pages = {476-478}, doi = {10.1016/s0140-6736(72)91867-3}, pmid = {4115357}, issn = {0140-6736}, mesh = {Asbestos/*adverse effects ; Asbestosis/complications ; Carcinoma, Bronchogenic/etiology/*mortality ; Drug Synergism ; Environmental Exposure ; Female ; Humans ; Lung Neoplasms/etiology/*mortality ; Male ; Mesothelioma/etiology/*mortality ; Nicotine/adverse effects ; Occupational Diseases ; Sex Factors ; Smoking/*complications ; }, } @article {pmid5048236, year = {1972}, author = {Selikoff, IJ and Hammond, EC and Churg, J}, title = {Carcinogenicity of amosite asbestos.}, journal = {Archives of environmental health}, volume = {25}, number = {3}, pages = {183-186}, doi = {10.1080/00039896.1972.10666158}, pmid = {5048236}, issn = {0003-9896}, mesh = {Adult ; Aged ; Asbestos/*toxicity ; Asbestosis/etiology/mortality ; *Carcinogens ; Environmental Exposure ; Humans ; Lung Neoplasms/chemically induced/mortality ; Male ; Mesothelioma/chemically induced/mortality ; Middle Aged ; Neoplasms/*chemically induced/mortality ; Occupational Diseases/*chemically induced ; Peritoneal Neoplasms/chemically induced ; Pleural Neoplasms/chemically induced ; United States ; }, } @article {pmid4564964, year = {1972}, author = {Bohlig, H and Dalquen, P and Hain, E}, title = {[Epidemiology of asbestos-induced diseases].}, journal = {Der Internist}, volume = {13}, number = {8}, pages = {318-325}, pmid = {4564964}, issn = {0020-9554}, mesh = {Asbestos/*adverse effects ; Asbestosis/*epidemiology ; Bronchial Neoplasms/chemically induced ; Carcinogens ; Environmental Exposure ; Female ; Germany, West ; Humans ; Intestinal Neoplasms/chemically induced ; Lipidoses/chemically induced ; Lung Neoplasms/epidemiology ; Male ; Mesothelioma/chemically induced/epidemiology ; Peritoneal Neoplasms/chemically induced ; Pleural Diseases/chemically induced ; Pleural Neoplasms/chemically induced ; Stomach Neoplasms/chemically induced ; Time Factors ; Tracheal Neoplasms/chemically induced ; Warts/chemically induced ; }, } @article {pmid4563250, year = {1972}, author = {}, title = {Mainly good news about asbestos.}, journal = {Food and cosmetics toxicology}, volume = {10}, number = {4}, pages = {574-578}, pmid = {4563250}, issn = {0015-6264}, mesh = {Animals ; *Asbestos/adverse effects ; Asbestosis/pathology ; Guinea Pigs ; Humans ; Ireland ; Lung Neoplasms/chemically induced/pathology ; Macrophages ; Mesothelioma/chemically induced/epidemiology/pathology ; Mice ; Phagocytosis ; Quebec ; Rats ; South Africa ; Stomach Neoplasms/chemically induced ; Time Factors ; }, } @article {pmid5044599, year = {1972}, author = {Harries, PG and Mackenzie, FA and Sheers, G and Kemp, JH and Oliver, TP and Wright, DS}, title = {Radiological survey of men exposed to asbestos in naval dockyards.}, journal = {British journal of industrial medicine}, volume = {29}, number = {3}, pages = {274-279}, pmid = {5044599}, issn = {0007-1072}, mesh = {Asbestosis/complications/diagnostic imaging/*epidemiology ; England ; Humans ; Lung Diseases/diagnostic imaging/*etiology ; Male ; Mesothelioma/etiology ; Middle Aged ; Naval Medicine ; Pleural Diseases/diagnostic imaging/*etiology ; Pleural Neoplasms/etiology ; Radiography ; Time Factors ; }, abstract = {Harries, P. G., Mackenzie, F. A. F., Sheers, G., Kemp, J. H., Oliver, T. P., and Wright, D. S. (1972).Brit. J. industr. Med.,29, 274-279. Radiological survey of men exposed to asbestos in naval dockyards. Asbestos related abnormalities were found in 3% of a 10% sample population in radiological surveys of the naval dockyards at Portsmouth, Chatham, and Rosyth. The prevalence of these abnormalities was related to the type of occupation and duration of exposure to asbestos. The results confirm the findings of an earlier survey at Devonport dockyard. No association between smoking, or the amount smoked, and the incidence of parenchymal or pleural disease due to asbestos was detected. Pleural abnormalities were found 10 times more frequently than parenchymal disease, and concern is felt over the uncertainty of the prognosis in men with pleural abnormalities, especially as 37 men have developed pleural mesothelioma at Devonport since 1965. More work is required to establish the true significance of pleural abnormalities caused by asbestos and to explore possible methods of treatment.}, } @article {pmid5033276, year = {1972}, author = {Selikoff, IJ and Nicholson, WJ and Langer, AM}, title = {Asbestos air pollution.}, journal = {Archives of environmental health}, volume = {25}, number = {1}, pages = {1-13}, doi = {10.1080/00039896.1972.10666125}, pmid = {5033276}, issn = {0003-9896}, mesh = {*Air Pollution ; *Asbestos/analysis ; Asbestosis/pathology ; Environmental Exposure ; Humans ; Lung/analysis/pathology ; Lung Neoplasms/chemically induced/pathology ; Mesothelioma/chemically induced/pathology ; Microscopy, Electron ; New York City ; }, } @article {pmid5043407, year = {1972}, author = {Wagner, JC}, title = {Significance of asbestos in lung tissue.}, journal = {Journal of clinical pathology}, volume = {25}, number = {6}, pages = {557}, doi = {10.1136/jcp.25.6.557-a}, pmid = {5043407}, issn = {0021-9746}, mesh = {*Asbestos ; Humans ; Lung Neoplasms/*chemically induced ; Mesothelioma/chemically induced ; Peritoneal Neoplasms/chemically induced ; Pleural Neoplasms/chemically induced ; }, } @article {pmid4664965, year = {1972}, author = {Pott, F and Huth, F and Friedrichs, KH}, title = {[Tumors of rats after i.p. injection of powdered chrysotile and benzo(a)pyrene].}, journal = {Zentralblatt fur Bakteriologie, Parasitenkunde, Infektionskrankheiten und Hygiene. Erste Abteilung Originale. Reihe B: Hygiene, praventive Medizin}, volume = {155}, number = {5}, pages = {463-469}, pmid = {4664965}, mesh = {Abdominal Neoplasms/*chemically induced ; Animals ; *Asbestos/administration & dosage ; *Benzopyrenes ; Carcinogens ; Dust ; Female ; Fibrosarcoma/chemically induced ; Industrial Waste ; Injections, Intraperitoneal ; Mesothelioma/chemically induced ; Rats ; Sarcoma/chemically induced ; }, } @article {pmid4557184, year = {1972}, author = {Nizze, H}, title = {[Asbestos and its hazards to man].}, journal = {Das Deutsche Gesundheitswesen}, volume = {27}, number = {20}, pages = {913-918}, pmid = {4557184}, issn = {0012-0219}, mesh = {*Asbestos ; *Asbestosis/complications/epidemiology/etiology/pathology ; Bronchial Neoplasms/etiology ; Dust ; Environmental Exposure ; Humans ; Lung/pathology ; Mesothelioma/etiology ; Pleural Neoplasms/etiology ; Respiration ; }, } @article {pmid4657953, year = {1972}, author = {Wagner, JC and Bogovski, P and Higginson, J}, title = {The role of international research in occupational cancer.}, journal = {La Medicina del lavoro}, volume = {63}, number = {5}, pages = {213-220}, pmid = {4657953}, issn = {0025-7818}, mesh = {Asbestos/adverse effects ; Asbestosis/*complications ; Bronchial Neoplasms/*etiology ; Humans ; Mesothelioma/etiology ; *Occupational Diseases ; Research ; }, } @article {pmid5070470, year = {1972}, author = {}, title = {Asbestos and health.}, journal = {Royal Society of Health journal}, volume = {92}, number = {2}, pages = {55-56}, doi = {10.1177/146642407209200202}, pmid = {5070470}, issn = {0035-9130}, mesh = {Asbestosis/complications/*epidemiology/prevention & control ; Humans ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; United Kingdom ; }, } @article {pmid5044507, year = {1972}, author = {Wagner, JC}, title = {Current opinions on the asbestos cancer problem.}, journal = {The Annals of occupational hygiene}, volume = {15}, number = {1}, pages = {61-65}, doi = {10.1093/annhyg/15.1.61}, pmid = {5044507}, issn = {0003-4878}, mesh = {Asbestos/*adverse effects ; Asbestosis/complications ; Carcinogens ; Humans ; Lung Neoplasms/*chemically induced/complications/mortality ; Mesothelioma/chemically induced/mortality ; Occupational Diseases/*chemically induced ; Occupational Medicine ; Pleural Neoplasms/chemically induced ; }, } @article {pmid5021995, year = {1972}, author = {Pooley, FD}, title = {Electron microscope characteristics of inhaled chrysotile asbestos fibre.}, journal = {British journal of industrial medicine}, volume = {29}, number = {2}, pages = {146-153}, pmid = {5021995}, issn = {0007-1072}, mesh = {Alkalies ; *Asbestos ; Asbestosis/*pathology ; Crystallography ; Dust ; Environmental Exposure ; Humans ; Lung/*pathology ; Mesothelioma/*pathology ; Microscopy, Electron ; *Occupational Medicine ; Rural Population ; Urban Population ; }, abstract = {Pooley, F. D. (1972).Brit. J. industr. Med.,29, 146-153. Electron microscope characteristics of inhaled chrysotile asbestos fibre. Specimens from 300 lungs have been examined under the electron microscope to determine the morphology and diffraction characteristics of any chrysotile asbestos they contained. In 120 cases, material was prepared by alkali digestion and the residual dust was examined. In all cases standard 6-micron histological slides were partially ashed before the residue was transferred to the electron microscope grids. Of the 300 specimens examined, 20 came from men with prolonged industrial exposure to chrysotile, 87 from cases of mesothelioma, and the remainder from control groups drawn from rural and industrial populations. Chrysotile fibres were readily identified by the characteristic polycrystalline diffraction pattern. The hollow appearance of the single fibres and their shape and arrangement also help in the identification. Specimens from men without industrial exposure contained either single short fibres or aggregates scattered throughout the lungs. In specimens from industrially exposed men, fibres were very numerous and found as strands of single fibres mainly grouped together in discrete locations. Ferruginous bodies were found rarely and only on straight fibre bundles of over several micrometers in length.}, } @article {pmid5021994, year = {1972}, author = {Fletcher, DE}, title = {A mortality study of shipyard workers with pleural plaques.}, journal = {British journal of industrial medicine}, volume = {29}, number = {2}, pages = {142-145}, pmid = {5021994}, issn = {0007-1072}, mesh = {Adult ; Aged ; *Asbestos ; Asbestosis/diagnostic imaging ; Bronchial Neoplasms/mortality ; England ; Environmental Exposure ; Humans ; Male ; Mass Chest X-Ray ; Mesothelioma/mortality ; Middle Aged ; *Mortality ; *Occupational Medicine ; Pleural Diseases/diagnostic imaging ; Pulmonary Fibrosis/diagnostic imaging ; Retrospective Studies ; Ships ; }, abstract = {Fletcher, D. E. (1972).Brit. J. industr. Med.,29, 142-145. A mortality study of shipyard workers with pleural plaques. Mild asbestos effects are seen frequently in shipyard workers. It is known that exposure of this type may be associated with mesothelioma, but it is not generally thought that an increased bronchial carcinoma risk exists unless there is pulmonary fibrosis. A number of cases of both types of malignant disease were seen in the Barrow hospitals, associated with pleural plaques. In view of this a retrospective survey was carried out. All routine administrative chest films taken in the works clinic between 1960 and 1970 were reviewed, together with the films of the 1962 mass radiography session, and 408 men were found to have evidence of pleural plaques. The men were followed up from the year of diagnosis until 1970 and 65 men died in this period. A similar control group of 404 men was chosen and 56 of them died. Both groups were compared with the expected mortality of Barrow men of the same age groups. There were 16 bronchial carcinomas in the plaque series compared with an expected figure of 6·74 (P = 0·0047), while in the control series there were 7 bronchial carcinomas compared with 5·61 expected (P = 0·516). Three mesotheliomas occurred in the plaque series (P = 0·0002).}, } @article {pmid5021993, year = {1972}, author = {Newhouse, ML and Berry, G and Wagner, JC and Turok, ME}, title = {A study of the mortality of female asbestos workers.}, journal = {British journal of industrial medicine}, volume = {29}, number = {2}, pages = {134-141}, pmid = {5021993}, issn = {0007-1072}, mesh = {Adult ; Age Factors ; *Asbestos ; Autopsy ; Environmental Exposure ; Female ; Humans ; Lung Neoplasms/mortality ; Mesothelioma/mortality ; *Mortality ; *Occupational Medicine ; Peritoneal Neoplasms/mortality ; Pleural Neoplasms/mortality ; Respiratory Tract Diseases/mortality ; Smoking ; *Textile Industry ; Time Factors ; United Kingdom ; }, abstract = {Newhouse, M. L., Berry, G., Wagner, J. C., and Turok, M. E. (1972).Brit. J. industr. Med.,29, 134-141. A study of the mortality of female asbestos workers. A cohort study of over 900 women employed at an asbestos factory making both textiles and insulation materials is described. It extends the information about asbestos-related disease at this factory which was previously available only for male workers. The cohort was defined as all the women who started employment at the factory between 1936 and 1942 and the main analysis was of mortality up to the end of 1968. This analysis was made in relation to job, length of exposure, and age at first exposure. Compared with national rates there was excess overall mortality among those who worked in jobs with low to moderate exposure partly accounted for by deaths from cancer. In the group with severe exposure, who had worked in the factory for less than two years, there was an excess of cancer of the lung and pleura. However, the most marked increased mortality was in those with severe exposure who had worked for more than two years in the factory; in this group there were excess deaths from cancer of the lung and pleura, from other cancers, and from respiratory diseases. There were no significant trends of excess mortality with age at first exposure. The smoking habits of some of the deceased women were obtained and the indications were that the proportion of smokers in the cohort was higher than the national rate. This could account for some of the excess mortality but the trend of this excess with exposure indicated the role of asbestos. Necropsy reports and/or histological material were obtained for 43% of those who had died. Three deaths registered as cancer of the pleura were identified as pleural mesothelial tumours; in all there were 11 mesotheliomas, six of pleural and five of peritoneal origin.}, } @article {pmid4551098, year = {1972}, author = {Woitowitz, HJ}, title = {[Importance of asbestos for industrial medicine and ecology].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {97}, number = {9}, pages = {346-351}, doi = {10.1055/s-0028-1107355}, pmid = {4551098}, issn = {0012-0472}, mesh = {Adult ; Air Pollution ; *Asbestos ; Asbestosis/complications/epidemiology ; *Ecology ; Environmental Exposure ; Germany, West ; Humans ; Lung Diseases, Obstructive/etiology ; Male ; Mesothelioma/chemically induced ; Middle Aged ; *Occupational Medicine ; Pleural Neoplasms/chemically induced ; Respiratory Function Tests ; Time Factors ; }, } @article {pmid5058974, year = {1972}, author = {Stanton, MF and Wrench, C}, title = {Mechanisms of mesothelioma induction with asbestos and fibrous glass.}, journal = {Journal of the National Cancer Institute}, volume = {48}, number = {3}, pages = {797-821}, pmid = {5058974}, issn = {0027-8874}, mesh = {Animals ; *Asbestos ; *Carcinogens ; Female ; *Glass ; Mesothelioma/*chemically induced/mortality/pathology ; Neoplasms, Experimental ; Nickel ; Pleural Diseases/chemically induced ; Pleural Neoplasms/*chemically induced/pathology ; Rats ; Silicon ; Stainless Steel ; }, } @article {pmid5050128, year = {1972}, author = {Gontier, F}, title = {[Asbestos dust, pleural calcifications and ship-building].}, journal = {Archives des maladies professionnelles de medecine du travail et de securite sociale}, volume = {23}, number = {3}, pages = {124-126}, pmid = {5050128}, issn = {0003-9691}, mesh = {Age Factors ; *Asbestosis/complications/diagnostic imaging ; *Calcinosis ; Humans ; Mesothelioma/etiology ; Middle Aged ; *Occupational Diseases ; *Pleural Diseases/diagnostic imaging ; Radiography ; }, } @article {pmid5042742, year = {1972}, author = {Pylev, LN}, title = {[Morphologic changes in the lungs of rats induced by intratracheal administration of chrysothyl-asbestos, alone and mixed with benz(alpha)pyrene].}, journal = {Voprosy onkologii}, volume = {18}, number = {6}, pages = {40-45}, pmid = {5042742}, issn = {0507-3758}, mesh = {Animals ; Asbestos/*toxicity ; *Benzopyrenes ; Bronchi/pathology ; *Drug Synergism ; Epithelium ; Hyperplasia ; Lung Diseases/chemically induced/pathology ; Lung Neoplasms/*chemically induced ; Mesothelioma/*chemically induced/pathology ; Neoplasm Metastasis ; Neoplasms, Experimental/*chemically induced ; Papilloma/*chemically induced ; Pleural Neoplasms/*chemically induced/pathology ; Precancerous Conditions/*chemically induced/pathology ; Rats ; }, } @article {pmid4664794, year = {1972}, author = {Wagner, JC}, title = {The significance of asbestos in tissue.}, journal = {Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer}, volume = {39}, number = {}, pages = {37-46}, pmid = {4664794}, issn = {0080-0015}, mesh = {Adenoma/*chemically induced ; Animals ; *Asbestos/administration & dosage ; Asbestosis/etiology ; Carcinoma, Squamous Cell/chemically induced ; Dose-Response Relationship, Drug ; Dust ; Environmental Exposure ; Injections ; Lung ; Lung Neoplasms/*chemically induced ; Mesothelioma/*chemically induced ; Oils ; Particle Size ; Peritoneal Neoplasms/chemically induced ; Pleural Neoplasms/chemically induced ; Rats ; Respiration ; Structure-Activity Relationship ; Time Factors ; }, } @article {pmid4640028, year = {1972}, author = {Knappmann, J}, title = {[Observations made at post mortem examination in 251 cases of mesothelioma in Hamburg (1958-1968)].}, journal = {Pneumonologie. Pneumonology}, volume = {148}, number = {1}, pages = {60-65}, pmid = {4640028}, issn = {0033-4073}, mesh = {Abdominal Neoplasms/*pathology ; Age Factors ; Asbestos ; Autopsy ; Bronchial Neoplasms/mortality ; Germany, West ; Humans ; Lymphatic Metastasis ; Mesothelioma/chemically induced/epidemiology/mortality/*pathology ; Neoplasm Metastasis ; Pleural Neoplasms ; Retrospective Studies ; Thoracic Neoplasms/epidemiology/*pathology ; }, } @article {pmid4335431, year = {1972}, author = {Stössel, HG and Dalquen, P and Carstens, U}, title = {[Pleural mesotheliomas in dockers].}, journal = {Fortschritte auf dem Gebiete der Rontgenstrahlen und der Nuklearmedizin}, volume = {116}, number = {1}, pages = {41-45}, pmid = {4335431}, issn = {0015-8151}, mesh = {Asbestos/*adverse effects ; Asbestosis/*complications ; Germany, West ; Humans ; Male ; Mesothelioma/*chemically induced/diagnosis/epidemiology ; Pleural Neoplasms/*chemically induced/diagnosis/epidemiology ; }, } @article {pmid5135107, year = {1971}, author = {Finlayson, A and McEwen, J and Mair, A}, title = {Home interviews with relatives of deceased persons: a means of obtaining histories of exposure to a hazardous substance.}, journal = {Scottish medical journal}, volume = {16}, number = {12}, pages = {509-512}, doi = {10.1177/003693307101601205}, pmid = {5135107}, issn = {0036-9330}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Environmental Exposure ; Family ; Female ; Humans ; Male ; *Medical History Taking ; Mesothelioma/epidemiology/*etiology ; Middle Aged ; Occupational Diseases/etiology ; Population Surveillance ; Respiratory Tract Neoplasms/epidemiology/*etiology ; Retrospective Studies ; Scotland ; }, } @article {pmid5126187, year = {1971}, author = {Oels, HC and Harrison, EG and Carr, DT and Bernatz, PE}, title = {Diffuse malignant mesothelioma of the pleura: a review of 37 cases.}, journal = {Chest}, volume = {60}, number = {6}, pages = {564-570}, doi = {10.1378/chest.60.6.564}, pmid = {5126187}, issn = {0012-3692}, mesh = {Adult ; Aged ; Asbestos ; Asbestosis/pathology ; Beryllium ; Environmental Exposure ; Female ; Humans ; Male ; Mesothelioma/etiology/mortality/*pathology ; Middle Aged ; Occupational Diseases/etiology ; Pleural Neoplasms/etiology/mortality/*pathology ; Pulmonary Fibrosis/pathology ; United States ; }, } @article {pmid5145770, year = {1971}, author = {Bittersohl, G and Ose, H}, title = {[Epidemiology of pleural mesothelioma].}, journal = {Zeitschrift fur die gesamte Hygiene und ihre Grenzgebiete}, volume = {17}, number = {11}, pages = {861-864}, pmid = {5145770}, issn = {0049-8610}, mesh = {Adult ; Age Factors ; Aged ; Asbestos/poisoning ; Germany, East ; Humans ; Male ; Mesothelioma/*chemically induced/epidemiology ; Middle Aged ; Occupational Diseases/epidemiology ; Pleural Neoplasms/*chemically induced/epidemiology ; }, } @article {pmid5159405, year = {1971}, author = {Milne, JE}, title = {Developmental changes in asbestos bodies and their significance.}, journal = {The Transactions of the Society of Occupational Medicine}, volume = {21}, number = {4}, pages = {118-121}, doi = {10.1093/occmed/21.4.118}, pmid = {5159405}, issn = {0037-9972}, mesh = {Asbestosis/*pathology ; Humans ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Microscopy, Electron ; Phagocytosis ; Sputum ; }, } @article {pmid5136837, year = {1971}, author = {Cralley, LJ}, title = {Electromotive phenomenon in metal and mineral particulate exposures: relevance to exposure to asbestos and occurrence of cancer.}, journal = {American Industrial Hygiene Association journal}, volume = {32}, number = {10}, pages = {653-661}, doi = {10.1080/0002889718506520}, pmid = {5136837}, issn = {0002-8894}, mesh = {Air Pollution ; Aluminum/analysis ; Animals ; *Asbestos/analysis/metabolism ; Carcinogens ; Chemical Phenomena ; Chemistry, Physical ; Chromium/analysis ; Cobalt/analysis ; Cricetinae ; Dust/analysis ; Environmental Exposure ; Humans ; Lung Neoplasms/chemically induced ; Manganese/analysis ; Mesothelioma/chemically induced ; *Metals/metabolism ; *Minerals/metabolism ; Mining ; Neoplasms/*chemically induced ; Nickel/analysis ; Occupational Diseases/*chemically induced ; Occupational Medicine ; Pleural Neoplasms/chemically induced ; Rats ; Textile Industry ; }, } @article {pmid5094056, year = {1971}, author = {Murphy, RL and Levine, BW and al-Bazzaz, FJ and Lynch, JJ and Burgess, WA}, title = {Floor tile installation as a source of asbestos exposure.}, journal = {The American review of respiratory disease}, volume = {104}, number = {4}, pages = {576-580}, doi = {10.1164/arrd.1971.104.4.576}, pmid = {5094056}, issn = {0003-0805}, mesh = {Adult ; Asbestosis/*etiology ; Biopsy ; Blood Glucose/analysis ; Calcinosis/etiology ; Dyspnea/etiology ; Environmental Exposure ; Erythrocyte Count ; Hemoptysis/etiology ; Histocytochemistry ; Humans ; Leukocyte Count ; Lung/diagnostic imaging ; Lung Neoplasms/etiology ; Male ; Mesothelioma/etiology ; Middle Aged ; Monocytes/analysis ; Pleural Effusion/pathology ; Pulmonary Diffusing Capacity ; Radiography ; Vital Capacity ; }, } @article {pmid5569319, year = {1971}, author = {Mackenzie, FA}, title = {The radiological investigation of the early manifestations of exposure to asbestos dust.}, journal = {Proceedings of the Royal Society of Medicine}, volume = {64}, number = {8}, pages = {834-837}, pmid = {5569319}, issn = {0035-9157}, mesh = {Asbestosis/*diagnostic imaging/epidemiology ; England ; Humans ; Male ; Mass Chest X-Ray ; Mesothelioma/diagnostic imaging ; Methods ; Naval Medicine ; Pleural Effusion/diagnostic imaging ; Pleural Neoplasms/diagnostic imaging ; Pulmonary Fibrosis/diagnostic imaging ; Technology, Radiologic ; }, } @article {pmid5569318, year = {1971}, author = {Lawther, PJ}, title = {Asbestos: some nonradiological aspects.}, journal = {Proceedings of the Royal Society of Medicine}, volume = {64}, number = {8}, pages = {833-834}, pmid = {5569318}, issn = {0035-9157}, mesh = {*Air Pollution ; *Asbestos/analysis ; Asbestosis/etiology/pathology/prevention & control ; Carcinogens/analysis ; Environmental Exposure ; Humans ; Lung/pathology ; Lung Neoplasms/*chemically induced ; Mesothelioma/chemically induced ; Pleural Neoplasms/chemically induced ; }, } @article {pmid4933176, year = {1971}, author = {Harrington, JS}, title = {Asbestos and mesothelioma in man.}, journal = {Nature}, volume = {232}, number = {5305}, pages = {54-55}, doi = {10.1038/232054a0}, pmid = {4933176}, issn = {0028-0836}, mesh = {Animals ; Asbestos/adverse effects ; Asbestosis/*complications ; Environmental Exposure ; Humans ; *Lung Neoplasms ; Mesothelioma/*chemically induced/epidemiology ; Mining ; Precancerous Conditions ; Rats ; South Africa ; }, } @article {pmid5571854, year = {1971}, author = {Gold, C}, title = {Asbestos in tumours.}, journal = {Journal of clinical pathology}, volume = {24}, number = {5}, pages = {481}, doi = {10.1136/jcp.24.5.481-d}, pmid = {5571854}, issn = {0021-9746}, mesh = {Animals ; Asbestos/adverse effects/*analysis ; Carcinoma, Bronchogenic/chemically induced ; Humans ; Lung Neoplasms/chemically induced ; Mesothelioma/chemically induced ; Neoplasms/chemically induced/*metabolism ; }, } @article {pmid5580634, year = {1971}, author = {Scheidemandel, V and Eisenstadt, HB and Gaensler, EA}, title = {Asbestos and mesothelioma.}, journal = {Annals of internal medicine}, volume = {74}, number = {6}, pages = {1014-1015}, doi = {10.7326/0003-4819-74-6-1014_2}, pmid = {5580634}, issn = {0003-4819}, mesh = {Asbestosis/*complications ; Environmental Exposure ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Pleural Effusion/*etiology ; }, } @article {pmid5574010, year = {1971}, author = {McDonald, JC and McDonald, AD and Gibbs, GW and Siemiatycki, J and Rossiter, CE}, title = {Mortality in the chrysotile asbestos mines and mills of Quebec.}, journal = {Archives of environmental health}, volume = {22}, number = {6}, pages = {677-686}, doi = {10.1080/00039896.1971.10665923}, pmid = {5574010}, issn = {0003-9896}, mesh = {Age Factors ; Aged ; Asbestos/*adverse effects ; Bronchial Neoplasms/epidemiology/*mortality ; Cardiovascular Diseases/epidemiology/mortality ; Dust/analysis ; Environmental Exposure ; Female ; Health Surveys ; Humans ; Lung Neoplasms/epidemiology/*mortality ; Male ; Mesothelioma/*mortality ; Middle Aged ; *Mining ; *Occupational Medicine ; Pneumoconiosis/epidemiology ; Quebec ; Registries ; Respiratory Tract Diseases/epidemiology/*mortality ; Retrospective Studies ; Time Factors ; Tracheal Neoplasms/epidemiology/*mortality ; }, } @article {pmid5089877, year = {1971}, author = {Champion, P}, title = {Two cases of malignant mesothelioma after exposure to asbestos.}, journal = {The American review of respiratory disease}, volume = {103}, number = {6}, pages = {821-826}, doi = {10.1164/arrd.1971.103.6.821}, pmid = {5089877}, issn = {0003-0805}, mesh = {Adult ; Asbestosis/*complications/diagnostic imaging/genetics ; Environmental Exposure ; Humans ; Lung Neoplasms/diagnostic imaging/*etiology ; Male ; Mesothelioma/diagnostic imaging/*etiology ; Radiography ; Smoking/complications ; }, } @article {pmid5556121, year = {1971}, author = {Roberts, GH}, title = {The pathology of parietal pleural plaques.}, journal = {Journal of clinical pathology}, volume = {24}, number = {4}, pages = {348-353}, pmid = {5556121}, issn = {0021-9746}, mesh = {Aged ; Asbestos/analysis ; Asbestosis/*pathology ; Humans ; Lung/analysis/pathology ; Male ; Mesothelioma/pathology ; Middle Aged ; Pleura/*pathology ; Pleural Neoplasms/pathology ; }, abstract = {The incidence, morbid anatomy, histology, and relationship of hyaline pleural plaques to exposure to asbestos has been studied. Plaques were found in 12.3% of 334 hospital necropsies (in an urban population in Glasgow, 41 cases). In 85.3% (35 cases) asbestos bodies were found in the lungs. There is evidence of a dose-response relationship between the number of asbestos bodies found in the lungs and the presence of pleural plaques. The selective distribution of plaques within the pleural cavities suggests that mechanical factors play a part in their localization. Histological examination contributed little to understanding the mechanism of plaque formation; that asbestos bodies have been detected in only a few cases suggest that their presence in the parietal pleura is not essential to plaque formation. The suggested mechanisms of plaque formation are discussed.}, } @article {pmid5157850, year = {1971}, author = {Wagner, JC}, title = {Asbestos cancers.}, journal = {Journal of the National Cancer Institute}, volume = {46}, number = {5}, pages = {V-IX}, pmid = {5157850}, issn = {0027-8874}, mesh = {Africa, Southern ; Asbestos/*adverse effects/classification ; Asbestosis/chemically induced/epidemiology ; Canada ; Humans ; Lung Neoplasms/*chemically induced ; Mesothelioma/chemically induced/epidemiology ; United States ; }, } @article {pmid5087573, year = {1971}, author = {Holmes, A and Morgan, A and Sandalls, J}, title = {Determination of iron, chromium, cobalt, nickel, and scandium in asbestos by neutron activation analysis.}, journal = {American Industrial Hygiene Association journal}, volume = {32}, number = {5}, pages = {281-286}, doi = {10.1080/0002889718506461}, pmid = {5087573}, issn = {0002-8894}, mesh = {Activation Analysis ; Asbestos/*analysis ; Asbestosis/complications ; Canada ; Chromium/*analysis ; Cobalt/*analysis ; Finland ; Humans ; Iron/*analysis ; Mesothelioma/etiology ; Mining ; Nickel/*analysis ; Pleural Neoplasms/etiology ; Scandium/*analysis ; South Africa ; Spectrometry, Gamma ; Trace Elements/analysis ; Zimbabwe ; }, } @article {pmid5572879, year = {1971}, author = {James, SA}, title = {Asbestosis.}, journal = {Radiography}, volume = {37}, number = {436}, pages = {81-85}, pmid = {5572879}, issn = {0033-8281}, mesh = {Adult ; Asbestos ; Asbestosis/complications/diagnosis/*diagnostic imaging ; Humans ; Male ; Mesothelioma/diagnostic imaging ; Middle Aged ; Mining ; Occupational Medicine ; Pleural Diseases/diagnostic imaging ; Pleural Neoplasms/diagnostic imaging ; Pulmonary Fibrosis/diagnostic imaging ; Radiography, Thoracic ; }, } @article {pmid4934612, year = {1971}, author = {}, title = {Asbestos: questions still unanswered.}, journal = {Food and cosmetics toxicology}, volume = {9}, number = {2}, pages = {281-284}, pmid = {4934612}, issn = {0015-6264}, mesh = {Animals ; Asbestos/*adverse effects ; Asbestosis/pathology ; Bronchial Neoplasms/chemically induced ; Hemolysis/drug effects ; Humans ; Lung/pathology ; Lung Neoplasms/chemically induced/pathology ; Mesothelioma/chemically induced ; Mining ; Occupational Diseases/*chemically induced ; Pleural Neoplasms/chemically induced ; Rats ; }, } @article {pmid5087349, year = {1971}, author = {Davis, JM}, title = {Epithelial outgrowths from lung tissue following intrapleural injection of asbestos dust in experimental animals.}, journal = {International journal of cancer}, volume = {7}, number = {2}, pages = {238-248}, doi = {10.1002/ijc.2910070207}, pmid = {5087349}, issn = {0020-7136}, mesh = {Animals ; *Asbestos ; Cell Transformation, Neoplastic ; Epithelium/pathology ; Granuloma/*chemically induced/pathology ; Guinea Pigs ; Lung/pathology ; Lung Neoplasms/*chemically induced/pathology ; Mesothelioma/*chemically induced/pathology ; Mice ; Microscopy, Electron ; Neoplasms, Experimental/chemically induced ; Pleural Neoplasms/*chemically induced/diagnosis/pathology ; Rats ; }, } @article {pmid5581686, year = {1971}, author = {}, title = {Asbestos and health, 1971.}, journal = {Royal Society of Health journal}, volume = {91}, number = {3}, pages = {55-56}, doi = {10.1177/146642407109100202}, pmid = {5581686}, issn = {0035-9130}, mesh = {Asbestos/*adverse effects ; Asbestosis/complications/prevention & control ; Humans ; Lung Neoplasms/chemically induced ; Mesothelioma/chemically induced ; Occupational Diseases/chemically induced ; Pleural Neoplasms/chemically induced ; Public Health Administration ; United Kingdom ; }, } @article {pmid5545226, year = {1971}, author = {Gaensler, EA and Kaplan, AI}, title = {Asbestos pleural effusion.}, journal = {Annals of internal medicine}, volume = {74}, number = {2}, pages = {178-191}, doi = {10.7326/0003-4819-74-2-178}, pmid = {5545226}, issn = {0003-4819}, mesh = {Adult ; Asbestosis/*complications/pathology/surgery ; Chronic Disease ; Diagnosis, Differential ; Follow-Up Studies ; Humans ; Lung/pathology ; Male ; Mesothelioma/etiology ; Middle Aged ; Pleura/pathology ; Pleural Effusion/diagnosis/*etiology/pathology/surgery ; Pulmonary Fibrosis/etiology ; Respiratory Function Tests ; }, } @article {pmid5542932, year = {1971}, author = {Lulenski, GC and Pifarré, R and Neville, WE}, title = {Rapid growth of a pleural mesothelioma.}, journal = {Chest}, volume = {59}, number = {2}, pages = {230-232}, doi = {10.1378/chest.59.2.230}, pmid = {5542932}, issn = {0012-3692}, mesh = {Asbestos/adverse effects ; Autopsy ; }, } @article {pmid5543628, year = {1971}, author = {Stumphius, J}, title = {Epidemiology of mesothelioma on Walcheren Island.}, journal = {British journal of industrial medicine}, volume = {28}, number = {1}, pages = {59-66}, pmid = {5543628}, issn = {0007-1072}, mesh = {Asbestos/*analysis ; }, abstract = {Stumphius, J. (1971). Brit. J. industr. Med., 28, 59-66. Epidemiology of mesothelioma on Walcheren Island. The chance finding of asbestos bodies without `asbestosis' in the lungs of a shipyard worker who had not worked directly with asbestos led to this investigation into the relationship between asbestos bodies in the sputum, occupation, and mesothelioma in the shipyard at Vlissingen on Walcheren Island. Examination of the sputum from a sample of 277 shipyard workers from various occupation groups (excluding insulation workers and others known to work continuously with asbestos) showed `asbestos' bodies to be present in 60%. The frequency varied from 39% in workers with no obvious exposure to asbestos dust to 100% among those with slight but definite exposure. By repeating the analysis using the occupations 5 to 10 years previously it was found that many of the workers currently employed in occupations not exposed to asbestos who had asbestos bodies in their sputum had been exposed in the past. Between 1962 and 1968, 25 cases of mesothelioma were discovered on Walcheren; of these, 22 cases had been employed in the shipyard at some time and their actual job was known in all but one case. The shipyard employs approximately 3 000 men so that the attack rate for mesothelioma was approximately 100 per 100 000 males per year. For Dutch provinces with heavy industry the rate is 1·0 per 100 000 per year. For the different occupational categories within the shipyard the rates varied from approximately 50 for `clean work' to 280 for men with some exposure to asbestos dust. Asbestos insulation workers were not included in the study and no cases of mesothelioma came from that occupational group.}, } @article {pmid5147638, year = {1971}, author = {Solheim, OP and Mathisen, O}, title = {[Mesothelioma and asbestos].}, journal = {Nordisk hygienisk tidskrift}, volume = {52}, number = {2}, pages = {53-59}, pmid = {5147638}, issn = {0029-1374}, mesh = {Adolescent ; Adult ; Aged ; Asbestos/*adverse effects ; Autopsy ; Female ; Humans ; Male ; Mesothelioma/*chemically induced/pathology ; Middle Aged ; Occupational Diseases ; Thoracic Neoplasms/*chemically induced/pathology ; Urinary Bladder Neoplasms/chemically induced ; }, } @article {pmid5145711, year = {1971}, author = {McEwen, J and Finlayson, A and Mair, A and Gibson, AA}, title = {Asbestos and mesothelioma in Scotland. An epidemiological study.}, journal = {Internationales Archiv fur Arbeitsmedizin}, volume = {28}, number = {4}, pages = {301-311}, pmid = {5145711}, issn = {0020-5923}, mesh = {Age Factors ; Asbestosis/*complications/epidemiology ; Environmental Exposure ; Female ; Humans ; Male ; Mesothelioma/*epidemiology/etiology ; Peritoneal Neoplasms/*epidemiology/etiology ; Pleural Neoplasms/*epidemiology/etiology ; Retrospective Studies ; Scotland ; Sex Factors ; }, } @article {pmid5101273, year = {1971}, author = {Whitwell, F and Rawcliffe, RM}, title = {Diffuse malignant pleural mesothelioma and asbestos exposure.}, journal = {Thorax}, volume = {26}, number = {1}, pages = {6-22}, pmid = {5101273}, issn = {0040-6376}, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Asbestosis/*complications/pathology ; Autopsy ; Humans ; }, abstract = {Pleural mesothelioma has been diagnosed in 52 patients in three hospitals on Merseyside between 1955 and 1970, 60% being diagnosed from operation specimens and the rest from postmortem tissues. Necropsies eventually held on nearly half the operation cases confirmed the diagnosis, giving a necropsy rate of 70% for the series. The morbid anatomy conformed to earlier descriptions except that widespread metastases were much commoner than has usually been described. Histological findings agreed with previous accounts of the tumour, except that, in our hands, special acid mucopolysaccharide staining was less reliable than Southgate's mucicarmine, which was of value in differential diagnosis. Association with asbestos was confirmed from industrial histories in 80% of cases, the commonest industries involved being shipbuilding and repairing in men and sackware repairing in women. Lungs of industrial mesothelioma cases showed basal asbestosis in 17% and excessive asbestos bodies in almost all the rest. Quantitative comparison of asbestos bodies in lung smears from mesothelioma cases compared with lung smears from other Merseyside adults showed much higher counts in the mesothelioma cases. The interval from first exposure to asbestos until appearance of mesothelioma ranged between 13 and 63 years, with a mean of 42 years. We think the incidence of mesothelioma will continue to rise with the increased use of asbestos until about 40 years after adequate protective measures have been taken.}, } @article {pmid5485174, year = {1970}, author = {McEwen, J and Finlayson, A and Mair, A and Gibson, AA}, title = {Mesothelioma in Scotland.}, journal = {British medical journal}, volume = {4}, number = {5735}, pages = {575-578}, pmid = {5485174}, issn = {0007-1447}, mesh = {Adult ; Aged ; Asbestos ; Biopsy ; Environmental Exposure ; Female ; Humans ; Male ; Mesothelioma/*epidemiology/pathology ; Middle Aged ; Occupations ; Peritoneal Neoplasms/*epidemiology/pathology ; Pleural Neoplasms/*epidemiology/pathology ; Retrospective Studies ; Scotland ; Smoking ; United Kingdom ; }, abstract = {In a retrospective study of the incidence of mesothelioma in Scotland for 1950-67 80 cases were traced from pathological reports and biopsy material of malignant tumours invading the pleura and peritoneum. These cases were matched with two sets of controls. Detailed histories of residence, occupation, and degree of exposure to asbestos confirmed that the incidence of mesothelioma in Scotland is similar to that in other parts of Britain.}, } @article {pmid5495964, year = {1970}, author = {Doll, R}, title = {Practical steps towards the prevention of bronchial carcinoma.}, journal = {Scottish medical journal}, volume = {15}, number = {12}, pages = {433-447}, doi = {10.1177/003693307001501202}, pmid = {5495964}, issn = {0036-9330}, mesh = {Adult ; Aged ; Air Pollution ; Arsenic/adverse effects ; Asbestos/adverse effects ; Asbestosis/complications ; Bronchial Neoplasms/chemically induced/epidemiology/etiology/mortality/*prevention & control ; Chromium/adverse effects ; Coal Tar/adverse effects ; Female ; Humans ; Lung Neoplasms/etiology/mortality ; Male ; Mesothelioma/etiology ; Middle Aged ; Mustard Compounds/adverse effects ; Nickel/adverse effects ; Occupational Diseases/etiology ; Radiation Injuries ; Smoking/complications ; United Kingdom ; }, } @article {pmid5489824, year = {1970}, author = {Solomon, A}, title = {Radiological features of diffuse mesothelioma.}, journal = {Environmental research}, volume = {3}, number = {4}, pages = {330-338}, doi = {10.1016/0013-9351(70)90026-5}, pmid = {5489824}, issn = {0013-9351}, mesh = {Asbestos/adverse effects ; Asbestosis/*complications ; Calcinosis/complications ; Environmental Exposure ; Female ; Humans ; Male ; Mesothelioma/*diagnostic imaging/etiology ; Mining ; Pleural Diseases/*complications ; Pleural Effusion/complications ; Pleural Neoplasms/*diagnostic imaging/etiology ; Pulmonary Fibrosis/complications ; Radiography ; Retrospective Studies ; South Africa ; }, } @article {pmid5533004, year = {1970}, author = {Roberts, GH}, title = {Diffuse pleural mesothelioma. A clinical and pathological study.}, journal = {British journal of diseases of the chest}, volume = {64}, number = {4}, pages = {201-211}, doi = {10.1016/s0007-0971(70)80016-x}, pmid = {5533004}, issn = {0007-0971}, mesh = {Adult ; Age Factors ; Aged ; Asbestos/adverse effects ; Asbestosis/complications ; Humans ; }, } @article {pmid5506612, year = {1970}, author = {McDonald, AD and Harper, A and McDonald, JC and el-Attar, OA}, title = {Epidemiology of primary malignant mesothelial tumors in Canada.}, journal = {Cancer}, volume = {26}, number = {4}, pages = {914-919}, doi = {10.1002/1097-0142(197010)26:4<914::aid-cncr2820260427>3.0.co;2-h}, pmid = {5506612}, issn = {0008-543X}, mesh = {Adolescent ; Adult ; Aged ; Asbestos/adverse effects ; Asbestosis/complications ; Autopsy ; Canada ; Child ; Child, Preschool ; Copper/adverse effects ; Female ; Heart Neoplasms/*epidemiology ; Humans ; Infant ; Lung Neoplasms/*epidemiology/etiology ; Male ; Mesothelioma/chemically induced/*epidemiology/etiology ; Middle Aged ; Nickel/adverse effects ; Occupational Diseases/chemically induced ; Peritoneal Neoplasms/*epidemiology ; Rubber/adverse effects ; Smoking/complications ; Surveys and Questionnaires ; Time Factors ; Wood/adverse effects ; }, } @article {pmid5483042, year = {1970}, author = {Hitchcock, HT}, title = {Mesothelioma of the pleura.}, journal = {Irish journal of medical science}, volume = {3}, number = {10}, pages = {453-456}, doi = {10.1007/BF02958985}, pmid = {5483042}, issn = {0021-1265}, mesh = {Adult ; Asbestos ; Humans ; Male ; Mesothelioma/*diagnosis ; Pleural Effusion/etiology ; Pleural Neoplasms/*diagnosis ; }, } @article {pmid5471312, year = {1970}, author = {Roberts, GH and Irvine, RW}, title = {Peritoneal mesothelioma. A report of 4 cases.}, journal = {The British journal of surgery}, volume = {57}, number = {9}, pages = {645-650}, doi = {10.1002/bjs.1800570903}, pmid = {5471312}, issn = {0007-1323}, mesh = {Abdomen ; Aged ; Asbestos ; Ascitic Fluid/cytology ; Biopsy ; Diagnosis, Differential ; Female ; Humans ; Liver/pathology ; Male ; Mesothelioma/*diagnosis/pathology ; Middle Aged ; Pain ; Peritoneal Cavity/pathology ; Peritoneal Neoplasms/*diagnosis/pathology ; }, } @article {pmid5421356, year = {1970}, author = {}, title = {[Pleural tumors].}, journal = {Les Cahiers de medecine}, volume = {11}, number = {6}, pages = {537-538}, pmid = {5421356}, issn = {0010-0978}, mesh = {Animals ; Asbestos ; Asbestosis/*complications ; Humans ; *Mesothelioma ; *Pleural Neoplasms ; }, } @article {pmid5422873, year = {1970}, author = {Avril, J and Champeix, J}, title = {[Results of exposure to asbestos in France].}, journal = {Archives des maladies professionnelles de medecine du travail et de securite sociale}, volume = {31}, number = {4}, pages = {197-200}, pmid = {5422873}, issn = {0003-9691}, mesh = {Asbestos/poisoning ; Asbestosis/*epidemiology ; Carcinoma, Bronchogenic/epidemiology ; France ; Humans ; Male ; Mesothelioma/epidemiology ; Occupational Diseases/*epidemiology ; Pleural Neoplasms/epidemiology ; }, } @article {pmid4911964, year = {1970}, author = {}, title = {Keen surveillance of asbestos still necessary.}, journal = {Food and cosmetics toxicology}, volume = {8}, number = {2}, pages = {207-210}, pmid = {4911964}, issn = {0015-6264}, mesh = {Animals ; Asbestos/*adverse effects/toxicity ; Asbestosis/etiology ; Cricetinae ; Humans ; Lung Neoplasms/chemically induced ; Mesothelioma/chemically induced ; Occupational Diseases ; Thrombosis/chemically induced ; }, } @article {pmid5490000, year = {1970}, author = {Dalquen, P and Hinz, I and Dabbert, AF}, title = {[Pleural plaques, asbestosis and exposure to asbestos. An epidemiological study from the Hamburg area].}, journal = {Pneumonologie. Pneumonology}, volume = {143}, number = {1}, pages = {23-42}, pmid = {5490000}, issn = {0033-4073}, mesh = {Adult ; Asbestosis/*epidemiology ; Dust ; Environmental Exposure ; Female ; Germany, West ; Humans ; Male ; Mesothelioma/complications/etiology ; Pleural Diseases/complications/diagnostic imaging/*epidemiology/etiology ; Pleural Neoplasms/complications/etiology ; Pulmonary Fibrosis/etiology ; Radiography ; Time Factors ; }, } @article {pmid5415904, year = {1970}, author = {Glage, E}, title = {[Malignant pleural mesothelioma of a female adult following exposure to asbestos in childhood].}, journal = {Praxis der Pneumologie}, volume = {24}, number = {1}, pages = {39-45}, pmid = {5415904}, issn = {0032-7069}, mesh = {Asbestosis/*complications ; Environmental Exposure ; Female ; Humans ; Mesothelioma/diagnostic imaging/*etiology/pathology ; Middle Aged ; Pleural Neoplasms/diagnostic imaging/*etiology/pathology ; Radiography ; }, } @article {pmid5387404, year = {1969}, author = {Henderson, WJ and Harse, J and Griffiths, K}, title = {A replication technique for the identification of asbestos fibres in mesotheliomas.}, journal = {European journal of cancer}, volume = {5}, number = {6}, pages = {621-624}, doi = {10.1016/0014-2964(69)90011-5}, pmid = {5387404}, issn = {0014-2964}, mesh = {Adult ; Aged ; Asbestos/*analysis ; Humans ; Male ; Mesothelioma/*pathology ; Methods ; Microscopy, Electron ; Middle Aged ; Pleura/pathology ; Pleural Neoplasms/*pathology ; }, } @article {pmid5373733, year = {1969}, author = {Longley, EO}, title = {The many faces of asbestos disease.}, journal = {The Medical journal of Australia}, volume = {2}, number = {21}, pages = {1063-1066}, doi = {10.5694/j.1326-5377.1969.tb107599.x}, pmid = {5373733}, issn = {0025-729X}, mesh = {Asbestos/adverse effects ; *Asbestosis ; Dust ; Environmental Exposure ; Female ; Humans ; Lung Neoplasms/etiology ; Male ; Mesothelioma/etiology ; Peritoneal Neoplasms/etiology ; Pleural Neoplasms/etiology ; }, } @article {pmid5348651, year = {1969}, author = {Milne, J}, title = {Fifteen cases of pleural mesothelioma associated with occupational exposure to asbestos in Victoria.}, journal = {The Medical journal of Australia}, volume = {2}, number = {14}, pages = {669-673}, doi = {10.5694/j.1326-5377.1969.tb107341.x}, pmid = {5348651}, issn = {0025-729X}, mesh = {Asbestos/*adverse effects ; Australia ; Environmental Exposure ; Female ; Humans ; Lung/pathology ; Male ; Mesothelioma/*etiology ; Occupational Diseases/*etiology/pathology ; Pleural Neoplasms/*etiology ; Time Factors ; }, } @article {pmid5346828, year = {1969}, author = {Newhouse, ML and Wagner, JC}, title = {Validation of death certificates in asbestos workers.}, journal = {British journal of industrial medicine}, volume = {26}, number = {4}, pages = {302-307}, pmid = {5346828}, issn = {0007-1072}, mesh = {Asbestos/adverse effects ; Asbestosis/*mortality/pathology ; Bronchial Neoplasms/pathology ; *Death Certificates ; Humans ; Intestinal Neoplasms/mortality ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/pathology ; Occupational Diseases/*mortality ; Peritoneal Neoplasms/mortality ; Pleural Neoplasms/mortality ; }, abstract = {Newhouse, M. L., and Wagner, J. C. (1969).Brit. J. industr. Med.,26, 302-307. Validation of death certificates in asbestos workers. The Registrar General has supplied the certified cause of death of 436 past workers in an asbestos factory. An attempt was made to follow up the 301 (69%) deaths which had occurred in hospital or had been the subject of an inquest or coroner's post-mortem examination. Necropsy reports were obtained for 158 (52%) of this group and histological material was reviewed in 84 (28%). The additional information, particularly that obtained from review of the histology, led to the revision and extension of the diagnosis suggested by the certified cause of death in a number of cases. The incidence of carcinoma of the bronchus had not been grossly underestimated, four additional tumours of this type were identified by scrutiny of the necropsy reports, and a further four by review of histological sections. The incidence of mesothelial tumours was underestimated, endothelioma or mesothelioma was the certified cause of death in four of the series, and a further 15 mesotheliomata were identified by review of histological material. Five patients with pleural mesotheliomata had been certified as dying of carcinoma of the lung or pleura. Ten deaths from peritoneal mesotheliomata had been attributed either to carcinomatosis without mention of a primary tumour or to cancer of the gastro-intestinal tract. Lung sections were submitted for review in 67 of the series; some degree of asbestosis was found in all but seven. Asbestosis graded as either moderate or severe was found in all the confirmed cases of carcinoma of the lung.}, } @article {pmid4900291, year = {1969}, author = {Wright, GW}, title = {Asbestos and health in 1969.}, journal = {The American review of respiratory disease}, volume = {100}, number = {4}, pages = {467-479}, doi = {10.1164/arrd.1969.100.4.467}, pmid = {4900291}, issn = {0003-0805}, mesh = {Air Pollution ; Asbestosis/*complications ; Carcinoma, Bronchogenic/*etiology ; Environmental Exposure ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/etiology ; Occupational Diseases ; Pulmonary Fibrosis/*etiology ; Talc ; }, } @article {pmid5360334, year = {1969}, author = {Berry, G and Wagner, JC}, title = {The application of a mathematical model describing the times of occurrence of mesotheliomas in rats following inoculation with asbestos.}, journal = {British journal of cancer}, volume = {23}, number = {3}, pages = {582-586}, pmid = {5360334}, issn = {0007-0920}, mesh = {Animals ; *Asbestos ; Injections ; Mesothelioma/*chemically induced/mortality ; *Models, Theoretical ; Neoplasms, Experimental/chemically induced ; Probability ; Rats ; }, } @article {pmid5360333, year = {1969}, author = {Wagner, JC and Berry, G}, title = {Mesotheliomas in rats following inoculation with asbestos.}, journal = {British journal of cancer}, volume = {23}, number = {3}, pages = {567-581}, pmid = {5360333}, issn = {0007-0920}, mesh = {Animals ; *Asbestos ; Female ; Injections ; Male ; Mesothelioma/*chemically induced/mortality/pathology ; Neoplasms, Experimental/chemically induced/pathology ; Rats ; }, } @article {pmid5352134, year = {1969}, author = {Dalquen, P and Dabbert, AF and Hinz, I}, title = {[Epidemiology of pleural mesotheliomas. Preliminary report on 119 clinical cases from the Hamburg area].}, journal = {Praxis der Pneumologie}, volume = {23}, number = {8}, pages = {547-558}, pmid = {5352134}, issn = {0032-7069}, mesh = {Adult ; Age Factors ; Aged ; *Asbestos ; Environmental Exposure ; Female ; Germany, West ; Humans ; Male ; Mesothelioma/chemically induced/*epidemiology ; Middle Aged ; Occupational Diseases/chemically induced ; Pleural Neoplasms/chemically induced/*epidemiology ; Sex Factors ; }, } @article {pmid5798645, year = {1969}, author = {Gold, C}, title = {Asbestos levels in human lungs.}, journal = {Journal of clinical pathology}, volume = {22}, number = {4}, pages = {507}, doi = {10.1136/jcp.22.4.507-b}, pmid = {5798645}, issn = {0021-9746}, mesh = {Asbestos/analysis ; Asbestosis/*pathology ; Bronchial Neoplasms/chemically induced ; Humans ; Lung/*analysis ; Lung Neoplasms/chemically induced ; Mesothelioma/chemically induced ; Minerals/*analysis ; }, } @article {pmid4980245, year = {1969}, author = {Le Bouffant, L and Daniel-Moussard, H and Durif, S and Martin, JC and Normand, C and Policard, A}, title = {[Research and characterization of asbestos particles in pleural mesotheliomas].}, journal = {Comptes rendus hebdomadaires des seances de l'Academie des sciences. Serie D: Sciences naturelles}, volume = {268}, number = {18}, pages = {2269-2274}, pmid = {4980245}, mesh = {Bronchial Neoplasms/chemically induced ; Chemical Phenomena ; Chemistry, Physical ; Electrons ; Lung Neoplasms/chemically induced ; Mesothelioma/*chemically induced ; Microscopy, Electron ; Pleural Neoplasms/*chemically induced ; X-Ray Diffraction ; }, } @article {pmid4910204, year = {1969}, author = {Dimov, D and Beritić, T}, title = {[Asbestos bodies in the lungs of urban population].}, journal = {Lijecnicki vjesnik}, volume = {91}, number = {9}, pages = {1003-1006}, pmid = {4910204}, issn = {0024-3477}, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Air Pollution ; *Asbestos/analysis ; Asbestosis/*diagnosis ; Environmental Exposure ; Ethnicity ; Female ; Humans ; Lung Neoplasms/epidemiology ; Male ; Mesothelioma/epidemiology ; Middle Aged ; Neoplasms/epidemiology ; Occupational Diseases/epidemiology ; Peritoneal Neoplasms/complications ; Pleural Neoplasms/complications ; Rural Population ; Sex Factors ; *Urban Population ; }, } @article {pmid5732325, year = {1968}, author = {}, title = {Getting to grips with asbestos.}, journal = {Food and cosmetics toxicology}, volume = {6}, number = {5}, pages = {657-659}, pmid = {5732325}, issn = {0015-6264}, mesh = {Animals ; Asbestos/toxicity ; Asbestosis/*chemically induced ; Environmental Exposure ; Guinea Pigs ; Humans ; Lung Neoplasms/chemically induced ; Mesothelioma/chemically induced ; Minerals/*toxicity ; Occupational Diseases/*chemically induced ; Rabbits ; }, } @article {pmid5732308, year = {1968}, author = {Roe, FJ}, title = {Experimental asbestos carcinogenesis.}, journal = {Food and cosmetics toxicology}, volume = {6}, number = {5}, pages = {566-568}, doi = {10.1016/0015-6264(68)90290-3}, pmid = {5732308}, issn = {0015-6264}, mesh = {Animals ; Asbestos ; Asbestosis/chemically induced ; Female ; Mesothelioma/*chemically induced ; Mice ; *Minerals ; Neoplasms, Experimental/chemically induced ; Sarcoma, Experimental/*chemically induced ; }, } @article {pmid5701835, year = {1968}, author = {Mortimer, RH and Campbell, CB}, title = {Asbestos exposure and pleural mesotheliomas.}, journal = {The Medical journal of Australia}, volume = {2}, number = {17}, pages = {720-722}, doi = {10.5694/j.1326-5377.1968.tb83135.x}, pmid = {5701835}, issn = {0025-729X}, mesh = {Asbestosis/*complications ; Humans ; Lung/pathology ; Male ; Mesothelioma/diagnosis/*etiology ; Middle Aged ; Pleural Neoplasms/diagnosis/*etiology ; }, } @article {pmid5723351, year = {1968}, author = {Knox, JF and Holmes, S and Doll, R and Hill, ID}, title = {Mortality from lung cancer and other causes among workers in an asbestos textile factory.}, journal = {British journal of industrial medicine}, volume = {25}, number = {4}, pages = {293-303}, pmid = {5723351}, issn = {0007-1072}, mesh = {Adult ; Age Factors ; Aged ; Asbestosis/*complications/mortality ; Bronchial Neoplasms/mortality ; Cardiovascular Diseases/mortality ; Dust ; Environmental Exposure ; Female ; Humans ; Lung Neoplasms/etiology/*mortality ; Male ; Mesothelioma/mortality ; Middle Aged ; Minerals ; Occupational Diseases/*mortality ; Respiratory Tract Diseases/mortality ; *Textile Industry ; Time Factors ; }, abstract = {An account is given of work in an asbestos textile factory and of the steps taken to reduce exposure to dust since the introduction of the Asbestos Industry Regulations in 1931. Measurements of the amount of dust to which men were exposed in the scheduled areas have been made by various methods since 1951, but the data obtained by these methods are not directly comparable. Measurements made since 1960 show that the mean yearly dust level has been fairly constant from year to year and has varied from place to place between 1 and 8 particles (5 to 100 microns long and at least three times as long as they were wide) per c.c. of air. Chrysotile was used predominantly in the factory, but small amounts of crocidolite were also processed at all relevant periods. Death rates have been recorded for all the 256 men who were employed for at least 20 years in the scheduled areas since the first man completed 20 years' exposure in 1916, and for the 538 men and 220 women who were employed for at least 10 years in the scheduled areas but were never employed in these areas before 1933. The results show a substantially increased mortality for men who were exposed for 10 or more years before 1933 (48 deaths from all causes against 17·1 expected). The increased mortality among these men can be accounted for by an increased mortality from cancer of the lung (12 deaths against 1·2 expected) and from diseases of the respiratory and circulatory systems associated with asbestosis. Men employed before 1933, but for less than 10 years, showed an increased mortality from lung cancer (5 deaths against 2·6 expected), but no significant increase from other causes. Men and women who were exposed only since January 1, 1933, have had a mortality experience close to the national average. Analysis of the trends in mortality shows (1) a decrease in mortality from lung cancer and other deaths associated with asbestosis with reduction in length of employment before 1933, and (2) an increase in mortality from lung cancer and other deaths without asbestosis with age. Twenty-three cases of lung cancer occurred in men who had been employed in the scheduled areas for at least 20 years. One was regarded as a pleural mesothelioma and the rest (approximately 18 in excess of expected) appear to have been ordinary bronchial carcinomas. Four other mesotheliomas have been diagnosed since 1963, all in men and women with less than 10 years' exposure, one with only seven months' exposure, and one in a man who had been employed in the scheduled areas only since 1937. The results provide grounds for believing that the occupational hazard of bronchial carcinoma has been largely eliminated, but the data are insufficient to estimate the extent of the risk which may remain.}, } @article {pmid5721712, year = {1968}, author = {Stumphius, J and Meyer, PB}, title = {Asbestos bodies and mesothelioma.}, journal = {The Annals of occupational hygiene}, volume = {11}, number = {4}, pages = {283-293}, doi = {10.1093/annhyg/11.4.283}, pmid = {5721712}, issn = {0003-4878}, mesh = {Asbestosis/*complications/pathology ; Humans ; Iron/poisoning ; Lung/pathology ; Male ; Mesothelioma/*chemically induced ; Microscopy, Electron ; Middle Aged ; Minerals/*poisoning ; Occupational Diseases ; Sputum/cytology ; }, } @article {pmid5667990, year = {1968}, author = {Sheers, G and Templeton, AR}, title = {Effects of asbestos in dockyard workers.}, journal = {British medical journal}, volume = {3}, number = {5618}, pages = {574-579}, pmid = {5667990}, issn = {0007-1447}, mesh = {Adolescent ; Adult ; Aged ; Asbestosis/diagnostic imaging/*epidemiology ; Carcinoma, Bronchogenic/epidemiology ; England ; Environmental Exposure ; Humans ; Male ; Mass Chest X-Ray ; Mesothelioma/epidemiology ; Middle Aged ; Occupational Diseases/epidemiology ; Pleural Diseases/epidemiology ; Pleural Neoplasms/epidemiology ; Pulmonary Fibrosis/epidemiology/etiology ; Time Factors ; Tuberculosis, Pulmonary/epidemiology ; }, abstract = {The prevalence of pleural and pulmonary abnormalities attributed to asbestos among 15,000 workers in a naval dockyard has been studied by means of a one-in-ten sample. Ninety-four per cent. of the men in the sample were examined. Of these, 3% had experienced continuous occupational exposure to asbestos and half of the remainder (representing approximately 6,800 men) had been exposed intermittently. The prevalence of pleural fibrosis ranged from 28% in continuously exposed workers to 1.9% in those with least exposure.Most cases of pulmonary fibrosis occurred in laggers and sprayers who had been continuously exposed for between 15 and 20 years. Pulmonary fibrosis was also seen in a variety of intermittently exposed trades, and had been preceded by extensive pleural thickening in some cases. Ten cases of pleural mesothelioma have occurred in the last three years and a large number of men appear to be potentially at risk.}, } @article {pmid5692054, year = {1968}, author = {Selikoff, IJ and Hammond, EC}, title = {Environmental epidemiology. 3. Community effects of nonoccupational environmental asbestos exposure.}, journal = {American journal of public health and the nation's health}, volume = {58}, number = {9}, pages = {1658-1666}, pmid = {5692054}, issn = {0002-9572}, mesh = {Adult ; *Air Pollution ; Asbestosis/*epidemiology/mortality/pathology ; Bronchial Neoplasms/etiology ; Bulgaria ; Canada ; Environment ; Environmental Exposure ; Female ; Finland ; Humans ; Male ; Mesothelioma/etiology ; Middle Aged ; New York City ; Northern Ireland ; Pleural Diseases/etiology ; South Africa ; United States ; }, } @article {pmid4916464, year = {1968}, author = {Meurman, LO}, title = {Pleural fibrocalcific plaques and asbestos exposure.}, journal = {Environmental research}, volume = {2}, number = {1}, pages = {30-46}, doi = {10.1016/0013-9351(68)90004-2}, pmid = {4916464}, issn = {0013-9351}, mesh = {Aged ; Asbestosis/*complications ; Calcinosis/*complications/etiology/pathology ; Humans ; Male ; Mesothelioma/complications ; Pleural Diseases/*complications/etiology/pathology ; Pulmonary Fibrosis ; Radiography, Thoracic ; }, } @article {pmid5666799, year = {1968}, author = {}, title = {Cancer and asbestos.}, journal = {British medical journal}, volume = {3}, number = {5616}, pages = {448-449}, pmid = {5666799}, issn = {0007-1447}, mesh = {Asbestosis/mortality/pathology ; Bronchial Neoplasms/*chemically induced ; Humans ; Male ; Mesothelioma/*chemically induced ; Middle Aged ; *Minerals ; Occupational Diseases/chemically induced ; }, } @article {pmid5671141, year = {1968}, author = {Bohlig, H}, title = {[Occupational and environmental hazards caused by asbestos].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {93}, number = {32}, pages = {1529-1531}, doi = {10.1055/s-0028-1110779}, pmid = {5671141}, issn = {0012-0472}, mesh = {Adult ; *Asbestosis/complications/diagnostic imaging ; Environmental Exposure ; Humans ; Lung/pathology ; Lung Neoplasms/etiology ; Male ; Mesothelioma/etiology ; Middle Aged ; Occupations ; Radiography ; }, } @article {pmid5721263, year = {1968}, author = {Royall, HJ}, title = {The health of the public and asbestos usage.}, journal = {The Royal Institute of Public Health and Hygiene journal}, volume = {31}, number = {4}, pages = {126-146}, pmid = {5721263}, mesh = {Adult ; Aged ; Asbestosis/*complications ; Environmental Exposure ; Female ; Humans ; Lung Neoplasms/*chemically induced ; Male ; Mesothelioma/*chemically induced ; Middle Aged ; Minerals/*toxicity ; Occupational Diseases/chemically induced ; }, } @article {pmid5694679, year = {1968}, author = {Godwin, MC and Jagatic, G}, title = {Asbestos and mesothelioma.}, journal = {JAMA}, volume = {204}, number = {11}, pages = {1009}, pmid = {5694679}, issn = {0098-7484}, mesh = {Animals ; *Asbestosis ; Humans ; Mesothelioma/*etiology ; Mice ; Occupational Diseases ; Rats ; }, } @article {pmid5648686, year = {1968}, author = {}, title = {Asbestos and neoplasia.}, journal = {South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde}, volume = {42}, number = {14}, pages = {325-326}, pmid = {5648686}, issn = {0256-9574}, mesh = {*Asbestosis ; Environmental Exposure ; Humans ; Mesothelioma/*chemically induced ; Neoplasms/*chemically induced ; *Occupational Diseases ; }, } @article {pmid5654330, year = {1968}, author = {}, title = {Hygiene standards for chrysotile asbestos dust.}, journal = {The Annals of occupational hygiene}, volume = {11}, number = {2}, pages = {47-69}, pmid = {5654330}, issn = {0003-4878}, mesh = {Air Pollution/*prevention & control ; Asbestosis/*prevention & control ; Dust/analysis ; Environmental Exposure ; Humans ; Lung Neoplasms/prevention & control ; Male ; Mesothelioma/prevention & control ; Physical Examination ; United Kingdom ; }, } @article {pmid5654326, year = {1968}, author = {Harries, PG}, title = {Asbestos hazards in naval dockyards.}, journal = {The Annals of occupational hygiene}, volume = {11}, number = {2}, pages = {135-145}, doi = {10.1093/annhyg/11.2.135}, pmid = {5654326}, issn = {0003-4878}, mesh = {Asbestosis/*prevention & control ; Dust/*analysis ; Environmental Exposure ; Humans ; Lung Neoplasms/prevention & control ; Male ; Mesothelioma/prevention & control ; United Kingdom ; }, } @article {pmid5637778, year = {1968}, author = {Castleman, B}, title = {Asbestos bodies in peritoneum.}, journal = {The New England journal of medicine}, volume = {278}, number = {11}, pages = {630}, pmid = {5637778}, issn = {0028-4793}, mesh = {*Asbestosis ; Humans ; Mesothelioma/pathology ; Peritoneal Neoplasms/pathology ; *Peritoneum ; }, } @article {pmid5637777, year = {1968}, author = {Levine, H}, title = {Asbestos bodies in peritoneum.}, journal = {The New England journal of medicine}, volume = {278}, number = {11}, pages = {630}, doi = {10.1056/NEJM196803142781126}, pmid = {5637777}, issn = {0028-4793}, mesh = {*Asbestosis ; Humans ; Mesothelioma/pathology ; Peritoneal Neoplasms/pathology ; *Peritoneum ; }, } @article {pmid5637571, year = {1968}, author = {Ashcroft, T}, title = {Asbestos bodies in routine necropsies on Tyneside: a pathological and social study.}, journal = {British medical journal}, volume = {1}, number = {5592}, pages = {614-618}, pmid = {5637571}, issn = {0007-1447}, mesh = {Adolescent ; Adult ; Aged ; Asbestosis/pathology ; England ; Female ; Humans ; Lung/*pathology ; Male ; Mesothelioma/pathology ; Middle Aged ; Minerals/*poisoning ; Occupational Diseases/pathology ; Socioeconomic Factors ; }, } @article {pmid4169796, year = {1968}, author = {}, title = {Pleural mesothelioma in an asbestos worker.}, journal = {Lancet (London, England)}, volume = {1}, number = {7540}, pages = {469}, pmid = {4169796}, issn = {0140-6736}, mesh = {Humans ; Jurisprudence ; Male ; Mesothelioma/etiology/*pathology ; Middle Aged ; *Minerals ; Occupational Diseases ; Pleural Neoplasms/etiology/*pathology ; }, } @article {pmid5650053, year = {1968}, author = {Polliack, A and Sacks, MI}, title = {Prevalence of asbestos bodies in basal lung smears.}, journal = {Israel journal of medical sciences}, volume = {4}, number = {2}, pages = {223-226}, pmid = {5650053}, issn = {0021-2180}, mesh = {*Air Pollution ; Asbestosis/*pathology ; Environmental Exposure ; Female ; Humans ; Jews ; Lung/*pathology ; Male ; Mesothelioma/etiology ; }, } @article {pmid5696358, year = {1968}, author = {Desbordes, J and Tayot, J and Dousset, G}, title = {[Reflections on the carcinogenic effect of asbestos].}, journal = {Le Poumon et le coeur}, volume = {24}, number = {5}, pages = {607-623}, pmid = {5696358}, issn = {0032-5821}, mesh = {Asbestosis/*complications ; Bronchial Neoplasms/*etiology ; Environmental Exposure ; Humans ; Mesothelioma/*etiology ; *Occupational Diseases ; Pleural Neoplasms/*etiology ; Time Factors ; }, } @article {pmid5696355, year = {1968}, author = {Planteydt, HT}, title = {[Mesothelioma and asbestos bodies in the expectoration of workers in a naval dockyard].}, journal = {Le Poumon et le coeur}, volume = {24}, number = {5}, pages = {545-548}, pmid = {5696355}, issn = {0032-5821}, mesh = {Asbestosis/*complications ; Environmental Exposure ; Humans ; Male ; Mesothelioma/*etiology ; Occupational Diseases/*complications ; Pleural Neoplasms/*etiology ; }, } @article {pmid5696354, year = {1968}, author = {Basset, F}, title = {[Asbestos bodies in the pleura of patients dying of diffuse pleural mesothelioma].}, journal = {Le Poumon et le coeur}, volume = {24}, number = {5}, pages = {537-543}, pmid = {5696354}, issn = {0032-5821}, mesh = {Asbestosis/*complications ; Humans ; Mesothelioma/*etiology/pathology ; Pleural Neoplasms/*etiology/pathology ; }, } @article {pmid5661522, year = {1968}, author = {Hägerstrand, I and Meurman, L and Odlund, B}, title = {Asbestos bodies in the lungs and mesothelioma. A retrospective examination of a ten-year-autopsy material.}, journal = {Acta pathologica et microbiologica Scandinavica}, volume = {72}, number = {2}, pages = {177-191}, pmid = {5661522}, issn = {0365-5555}, mesh = {Adolescent ; Adult ; Aged ; Asbestosis/*complications/pathology ; Female ; Humans ; Lung/pathology ; Male ; Mesothelioma/complications/epidemiology/*pathology ; Middle Aged ; Neoplasm Metastasis/epidemiology ; Occupations ; Peritoneal Neoplasms/complications/epidemiology/*pathology ; Pleural Neoplasms/complications/epidemiology/*pathology ; }, } @article {pmid5661213, year = {1968}, author = {Rusby, NL}, title = {Pleural manifestations following the inhalation of asbestos in relation to malignant change.}, journal = {Journal of the Royal Naval Medical Service}, volume = {54}, number = {2}, pages = {142-148}, pmid = {5661213}, issn = {0035-9033}, mesh = {Aged ; Asbestosis/*complications ; Environmental Exposure ; Female ; Humans ; Male ; Mesothelioma/*etiology ; Middle Aged ; Peritoneal Neoplasms/etiology ; Pleural Diseases/*complications ; Pleural Neoplasms/*etiology ; }, } @article {pmid5582282, year = {1967}, author = {Roe, FJ and Carter, RL and Walters, MA and Harington, JS}, title = {The pathological effects of subcutaneous injections of asbestos fibres in mice: migration of fibres to submesothelial tissues and induction of mesotheliomata.}, journal = {International journal of cancer}, volume = {2}, number = {6}, pages = {628-638}, doi = {10.1002/ijc.2910020624}, pmid = {5582282}, issn = {0020-7136}, mesh = {Animals ; Female ; Injections, Subcutaneous ; Mesothelioma/*chemically induced ; Mice ; Minerals/*pharmacology ; Sarcoma, Experimental/chemically induced ; Serous Membrane/*pathology ; }, } @article {pmid5628974, year = {1967}, author = {Graham, J and Graham, R}, title = {Ovarian cancer and asbestos.}, journal = {Environmental research}, volume = {1}, number = {2}, pages = {115-128}, doi = {10.1016/0013-9351(67)90008-4}, pmid = {5628974}, issn = {0013-9351}, mesh = {Animals ; Asbestosis/complications ; Carcinoma/pathology ; Cricetinae ; Environmental Exposure ; Epithelium/pathology ; Female ; Foreign Bodies/pathology ; Guinea Pigs ; Humans ; Mesothelioma/chemically induced ; Mice ; Minerals/*adverse effects ; Neoplasms, Experimental ; Ovarian Neoplasms/*chemically induced/pathology ; Ovary/pathology ; Rabbits ; }, } @article {pmid6035084, year = {1967}, author = {Gross, P and DeTreville, RT and Tolker, EB and Kaschak, M and Babyak, MA}, title = {Experimental asbestosis. The development of lung cancer in rats with pulmonary deposits of chrysotile asbestos dust.}, journal = {Archives of environmental health}, volume = {15}, number = {3}, pages = {343-355}, doi = {10.1080/00039896.1967.10664930}, pmid = {6035084}, issn = {0003-9896}, mesh = {Adenocarcinoma/chemically induced ; Animals ; Asbestosis/*complications ; Carcinoma, Squamous Cell/chemically induced ; Caustics ; Chromium ; Cobalt ; Dust ; Fibrosarcoma/chemically induced ; Lead ; Lung/pathology ; Lung Neoplasms/*chemically induced/mortality ; Male ; Mesothelioma/chemically induced ; Metaplasia/chemically induced ; Minerals ; Nickel ; Papilloma/chemically induced ; Rats ; }, } @article {pmid4864688, year = {1967}, author = {Norwood, WD and Fuqua, PA and Mancuso, TF}, title = {Asbestos--an environmental health hazard.}, journal = {Northwest medicine}, volume = {66}, number = {9}, pages = {821-828}, pmid = {4864688}, issn = {0029-3385}, mesh = {Asbestosis/*complications ; Humans ; Lung Neoplasms/etiology ; Male ; Mesothelioma/etiology ; Middle Aged ; Pulmonary Fibrosis/etiology ; }, } @article {pmid6051099, year = {1967}, author = {Harington, JS and Roe, FJ and Walters, M}, title = {Studies of the mode of action of asbestos as a carcinogen.}, journal = {South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde}, volume = {41}, number = {32}, pages = {800-804}, pmid = {6051099}, issn = {0256-9574}, mesh = {Animals ; Asbestosis/complications ; Lung Neoplasms/*chemically induced ; Mesothelioma/*chemically induced ; Mice ; Minerals ; Neoplasms, Experimental ; Oils/adverse effects ; Pleural Neoplasms/*chemically induced ; Rats ; South Africa ; }, } @article {pmid5631751, year = {1967}, author = {Cuthbert, J}, title = {[The hazards of asbestos for the community].}, journal = {Munchener medizinische Wochenschrift (1950)}, volume = {109}, number = {25}, pages = {1369-1372}, pmid = {5631751}, issn = {0027-2973}, mesh = {*Asbestosis ; Humans ; Lung Neoplasms ; Mesothelioma ; *Occupational Diseases ; Pulmonary Fibrosis ; }, } @article {pmid4165161, year = {1967}, author = {}, title = {Control of the asbestos hazard.}, journal = {Lancet (London, England)}, volume = {1}, number = {7503}, pages = {1311-1312}, pmid = {4165161}, issn = {0140-6736}, mesh = {Asbestosis/*prevention & control ; Humans ; *Legislation as Topic ; Mesothelioma/chemically induced ; United Kingdom ; }, } @article {pmid6024480, year = {1967}, author = {Lieben, J and Pistawka, H}, title = {Mesothelioma and asbestos exposure.}, journal = {Archives of environmental health}, volume = {14}, number = {4}, pages = {559-563}, doi = {10.1080/00039896.1967.10664792}, pmid = {6024480}, issn = {0003-9896}, mesh = {Adult ; Aged ; Asbestosis/*complications ; Female ; Humans ; Male ; Mesothelioma/*etiology ; Middle Aged ; Occupational Diseases/*complications ; Pennsylvania ; Peritoneal Neoplasms/*etiology ; Pleural Neoplasms/*etiology ; }, } @article {pmid5981209, year = {1966}, author = {Bohlig, H}, title = {[Disease symptoms after asbestos dust inhalation].}, journal = {Zentralblatt fur Arbeitsmedizin und Arbeitsschutz}, volume = {16}, number = {12}, pages = {353-355}, pmid = {5981209}, issn = {0044-4049}, mesh = {Asbestosis/*complications/mortality ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; }, } @article {pmid5992311, year = {1966}, author = {Tayot, J and Desbordes, J and Ernoult, JL and Potoine, B}, title = {[Pleural mesothelioma and asbestos].}, journal = {Journal francais de medecine et chirurgie thoraciques}, volume = {20}, number = {7}, pages = {757-773}, pmid = {5992311}, issn = {0021-8324}, mesh = {Asbestosis/*complications ; Female ; Humans ; Middle Aged ; Pleural Neoplasms/*etiology ; Sarcoma/*etiology ; }, } @article {pmid5912329, year = {1966}, author = {O'Donnell, WM and Mann, RH and Grosh, JL}, title = {Asbestos, an extrinsic factor in the pathogenesis of bronchogenic carcinoma and mesothelioma.}, journal = {Cancer}, volume = {19}, number = {8}, pages = {1143-1148}, doi = {10.1002/1097-0142(196608)19:8<1143::aid-cncr2820190815>3.0.co;2-5}, pmid = {5912329}, issn = {0008-543X}, mesh = {Adult ; Aged ; Carcinoma, Bronchogenic/*etiology ; Carcinoma, Squamous Cell/*etiology ; Female ; Humans ; Male ; Mesothelioma/*etiology ; Middle Aged ; Textile Industry ; }, } @article {pmid5988284, year = {1966}, author = {Thomson, JG and Graves, WM}, title = {Asbestos as an urban air contaminant.}, journal = {Archives of pathology}, volume = {81}, number = {5}, pages = {458-464}, pmid = {5988284}, issn = {0363-0153}, mesh = {Adolescent ; Adult ; Aged ; *Air Pollution ; *Asbestosis ; Female ; Humans ; Male ; Mesothelioma/etiology ; Middle Aged ; Occupational Medicine ; Peritoneal Neoplasms/etiology ; Pleural Neoplasms/etiology ; }, } @article {pmid5902378, year = {1966}, author = {Hill, ID and Doll, R and Knox, JF}, title = {Mortality among asbestos workers.}, journal = {Proceedings of the Royal Society of Medicine}, volume = {59}, number = {1}, pages = {59-60}, pmid = {5902378}, issn = {0035-9157}, mesh = {Adult ; Asbestosis/*complications ; England ; Female ; Humans ; Lung Neoplasms/*etiology ; Male ; Mesothelioma/etiology ; Mortality ; Pleural Neoplasms/etiology ; }, } @article {pmid5902377, year = {1966}, author = {Smither, WJ}, title = {Asbestos, asbestosis and mesothelioma of the pleura.}, journal = {Proceedings of the Royal Society of Medicine}, volume = {59}, number = {1}, pages = {57-59}, pmid = {5902377}, issn = {0035-9157}, mesh = {Abdominal Neoplasms/etiology ; Asbestosis/*complications/diagnosis/*epidemiology ; Humans ; Mesothelioma/*etiology ; Pleural Neoplasms/*etiology ; }, } @article {pmid5219881, year = {1965}, author = {McCaughey, WT}, title = {Asbestos and neoplasia: diffuse mesothelial tumors. Criteria for diagnosis of diffuse mesothelial tumors.}, journal = {Annals of the New York Academy of Sciences}, volume = {132}, number = {1}, pages = {603-613}, doi = {10.1111/j.1749-6632.1965.tb41140.x}, pmid = {5219881}, issn = {0077-8923}, mesh = {Asbestosis/*complications ; Humans ; In Vitro Techniques ; Mesothelioma/diagnosis/*pathology ; Pleural Neoplasms/diagnosis/*pathology ; }, } @article {pmid5219584, year = {1965}, author = {}, title = {Report and recommendations of the working group on asbestos and cancer; convened under the auspices of the Geographical Pathology Section of the International Union against Cancer.}, journal = {Annals of the New York Academy of Sciences}, volume = {132}, number = {1}, pages = {706-721}, pmid = {5219584}, issn = {0077-8923}, mesh = {Asbestosis/epidemiology/pathology/*prevention & control ; Epidemiologic Methods ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Peritoneal Neoplasms/*etiology ; Pleural Neoplasms/*etiology ; }, } @article {pmid5219583, year = {1965}, author = {Gilson, JC}, title = {Problems and perspectives: the changing hazards of exposure to asbestos.}, journal = {Annals of the New York Academy of Sciences}, volume = {132}, number = {1}, pages = {696-705}, doi = {10.1111/j.1749-6632.1965.tb41148.x}, pmid = {5219583}, issn = {0077-8923}, mesh = {Asbestosis/complications/*epidemiology ; Bronchial Neoplasms/etiology ; Humans ; Mesothelioma/etiology ; Peritoneal Neoplasms/etiology ; Pleural Neoplasms/etiology ; }, } @article {pmid5219582, year = {1965}, author = {Wagner, JC}, title = {The sequelae of exposure to asbestos dust.}, journal = {Annals of the New York Academy of Sciences}, volume = {132}, number = {1}, pages = {691-695}, doi = {10.1111/j.1749-6632.1965.tb41147.x}, pmid = {5219582}, issn = {0077-8923}, mesh = {Animals ; Asbestosis/complications/etiology/*pathology ; Humans ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Peritoneal Neoplasms/etiology ; Pleural Neoplasms/etiology ; }, } @article {pmid5219580, year = {1965}, author = {Owen, WG}, title = {Mesothelial tumors and exposure to asbestos dust.}, journal = {Annals of the New York Academy of Sciences}, volume = {132}, number = {1}, pages = {674-679}, doi = {10.1111/j.1749-6632.1965.tb41144.x}, pmid = {5219580}, issn = {0077-8923}, mesh = {Adult ; Aged ; Asbestosis/*complications ; Female ; Humans ; In Vitro Techniques ; Male ; Mesothelioma/*etiology ; Middle Aged ; Peritoneal Neoplasms/*etiology ; Pleural Neoplasms/*etiology ; }, } @article {pmid5219579, year = {1965}, author = {Hourihane, DO}, title = {A biopsy series of mesotheliomata, and attempts to identify asbestos within some of the tumors.}, journal = {Annals of the New York Academy of Sciences}, volume = {132}, number = {1}, pages = {647-673}, doi = {10.1111/j.1749-6632.1965.tb41143.x}, pmid = {5219579}, issn = {0077-8923}, mesh = {Asbestosis/*complications ; Biopsy ; Humans ; In Vitro Techniques ; Mesothelioma/*pathology ; *Minerals ; Peritoneal Neoplasms/*pathology ; Pleural Neoplasms/*pathology ; }, } @article {pmid5219574, year = {1965}, author = {Elmes, PC and Wade, OL}, title = {Relationship between exposure to asbestos and pleural malignancy in Belfast.}, journal = {Annals of the New York Academy of Sciences}, volume = {132}, number = {1}, pages = {549-557}, doi = {10.1111/j.1749-6632.1965.tb41135.x}, pmid = {5219574}, issn = {0077-8923}, mesh = {Adult ; Aged ; Asbestosis/*complications ; Humans ; Male ; Mesothelioma/*etiology ; Middle Aged ; Mortality ; Northern Ireland ; Pleural Neoplasms/*epidemiology ; }, } @article {pmid5219568, year = {1965}, author = {Smith, WE and Miller, L and Elsasser, RE and Hubert, DD}, title = {Tests for carcinogenicity of asbestos.}, journal = {Annals of the New York Academy of Sciences}, volume = {132}, number = {1}, pages = {456-488}, doi = {10.1111/j.1749-6632.1965.tb41127.x}, pmid = {5219568}, issn = {0077-8923}, mesh = {Animals ; Asbestosis/complications ; *Carcinogens ; Cricetinae ; In Vitro Techniques ; Injections ; Male ; Mesothelioma/*etiology ; Minerals/*adverse effects ; Neoplasms, Experimental/etiology ; Pleura/pathology ; Pleural Diseases/etiology ; Pleural Neoplasms/*etiology ; Tissue Adhesions/etiology ; Trachea ; }, } @article {pmid5219566, year = {1965}, author = {Harington, JS and Roe, FJ}, title = {Studies of carcinogenesis of asbestos fibers and their natural oils.}, journal = {Annals of the New York Academy of Sciences}, volume = {132}, number = {1}, pages = {439-450}, doi = {10.1111/j.1749-6632.1965.tb41125.x}, pmid = {5219566}, issn = {0077-8923}, mesh = {Animals ; Asbestosis/*complications/*pathology ; *Carcinogens ; Chemical Phenomena ; Chemistry ; Humans ; Iron/adverse effects ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Metals/adverse effects ; Mice ; Minerals/*adverse effects ; Oils ; Pleural Neoplasms/*etiology ; Rats ; }, } @article {pmid4222863, year = {1965}, author = {Churg, J and Rosen, SH and Moolten, S}, title = {Histological characteristics of mesothelioma associated with asbestos.}, journal = {Annals of the New York Academy of Sciences}, volume = {132}, number = {1}, pages = {614-622}, doi = {10.1111/j.1749-6632.1965.tb41141.x}, pmid = {4222863}, issn = {0077-8923}, mesh = {Asbestosis/*complications ; Chemical Phenomena ; Chemistry ; *Glycosaminoglycans ; Humans ; In Vitro Techniques ; Mesothelioma/*pathology ; Peritoneal Neoplasms/*pathology ; Pleural Neoplasms/*pathology ; }, } @article {pmid5836565, year = {1965}, author = {Newhouse, ML and Thompson, H}, title = {Mesothelioma of pleura and peritoneum following exposure to asbestos in the London area.}, journal = {British journal of industrial medicine}, volume = {22}, number = {4}, pages = {261-269}, pmid = {5836565}, issn = {0007-1072}, mesh = {Adult ; Aged ; Asbestosis/*complications ; England ; Female ; Humans ; Male ; Mesothelioma/*etiology ; Middle Aged ; Mortality ; Occupational Diseases ; Peritoneal Neoplasms/*etiology ; Pleural Neoplasms/*etiology ; }, abstract = {A series of 83 patients from the London Hospital with a diagnosis of mesothelioma confirmed by necropsy or biopsy has been studied for possible exposure to asbestos. The series consisted of 41 men and 42 women; 27 of the patients had peritoneal and 56 pleural tumours. The earliest death recorded was in 1917, but only 10 of the series died before 1950 and 40 (48%) between 1960 and 1964. In 76 of the series full occupational and residential histories were obtained. Forty (52·6%) gave a history of occupational or domestic (living in the same house as an asbestos worker) exposure to asbestos compared with nine (11·8%) out of 76 patients from the same hospital suffering from other diseases (p < 0·001). None of the 17 suspected cases of mesothelioma, rejected on pathological grounds, was found to have had any exposure to asbestos. There was also evidence that neighbourhood exposures may be important. Among those with no evidence of occupational or domestic exposures, 30·6% of the mesothelioma patients and 7·6% of the in-patients with other diseases lived within half a mile of an asbestos factory (p < 0·01). Out of the 31 patients with occupational exposures only 10 were in jobs scheduled under the Asbestos Regulations of 1931. The interval between first exposure and the development of the terminal illness of mesothelioma ranged between 16 and 55 years. In 47 patients in the mesothelioma series, lung tissue or sputum was available for examination. In 30 (62·5%), either asbestosis or asbestos bodies were present.}, } @article {pmid5832253, year = {1965}, author = {}, title = {Working Group on Asbestos and Cancer. Report and recommendations of the Working Group convened under the auspices of the Geographical Pathology Committee of the International Union against Cancer.}, journal = {Archives of environmental health}, volume = {11}, number = {2}, pages = {221-229}, pmid = {5832253}, issn = {0003-9896}, mesh = {Animals ; Asbestosis/*complications/pathology/prevention & control ; Chemistry Techniques, Analytical ; Classification ; Cytodiagnosis ; Histocytochemistry ; Humans ; In Vitro Techniques ; Lung Neoplasms/*etiology ; Mesothelioma/diagnosis/*etiology/pathology ; Neoplasms, Experimental ; Occupational Medicine ; Peritoneal Neoplasms/*etiology ; Physical Phenomena ; Physics ; Pleural Neoplasms/*etiology ; Radiography, Thoracic ; }, } @article {pmid4286110, year = {1965}, author = {Hardy, HL}, title = {Asbestos-related disease.}, journal = {Transactions of the Association of American Physicians}, volume = {78}, number = {}, pages = {204-217}, pmid = {4286110}, issn = {0066-9458}, mesh = {Adenocarcinoma/etiology ; *Asbestosis ; Female ; Humans ; In Vitro Techniques ; Lung Diseases/*pathology ; Lung Neoplasms/*etiology ; Male ; Mesothelioma/*etiology ; Middle Aged ; Silicon Dioxide/*adverse effects ; }, } @article {pmid1451080, year = {1992}, author = {Sridhar, KS and Doria, R and Raub, WA and Thurer, RJ and Saldana, M}, title = {New strategies are needed in diffuse malignant mesothelioma.}, journal = {Cancer}, volume = {70}, number = {12}, pages = {2969-2979}, doi = {10.1002/1097-0142(19921215)70:12<2969::aid-cncr2820701239>3.0.co;2-a}, pmid = {1451080}, issn = {0008-543X}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Mesothelioma/drug therapy/mortality/*therapy ; Middle Aged ; Multicenter Studies as Topic ; Prognosis ; }, abstract = {BACKGROUND: Medical records of 50 patients with malignant mesothelioma were reviewed to determine the clinical features and factors influencing survival.

METHODS: Charts of all patients whose conditions were diagnosed as malignant mesothelioma were abstracted and analyzed by statistical software.

RESULTS: The male-to-female ratio was 4:1. The age distribution was younger than 45 years of age, 10%; 45-54 years of age, 12%; 55-64 years of age, 37%; 65-74 years of age, 33%; and 75 years of age or older, 8%. Both mean and median ages were 58 years. Among the 32 patients in whom asbestos exposure was recorded, 24 had documented exposure. The sites were pleura, 73%; peritoneum, 20%; and both, 6%. The histologic types were epithelial, 51%; sarcomatous, 10%; mixed, 15%; and not specified, 24%. The stage at presentation was Stage I, 37%; II, 39%; III, 12%; IV, 6%; and unknown, 6%. The common symptoms in pleural disease were dyspnea and pain; in peritoneal disease, abdominal distension and pain were common. The median time from first symptom to diagnosis was 3 months (range, 0-23 months). The median survival after the appearance of symptoms, the diagnosis, and the treatment were 13, 10, and 8 months, respectively.

CONCLUSIONS: The survival was independent of age, sex, and smoking behavior. It was longer in patients with earlier-stage disease, a good performance status, a longer duration of symptoms, an absence of pain, and who were treated with combined surgery and chemotherapy. Chemotherapy using anthracyclines yielded more remissions (9 of 21) than that using nonanthracyclines (0 of 13). The remission rate after primary chemotherapy with anthracyclines (7 of 16) may be higher than in recurrent tumor (2 of 14). In future trials, stratification into primary chemotherapy and chemotherapy of recurrent cancer is suggested. There is a need for multitechnique trials incorporating primary chemotherapy.}, } @article {pmid1459729, year = {1992}, author = {Davis, MR and Manning, LS and Whitaker, D and Garlepp, MJ and Robinson, BW}, title = {Establishment of a murine model of malignant mesothelioma.}, journal = {International journal of cancer}, volume = {52}, number = {6}, pages = {881-886}, doi = {10.1002/ijc.2910520609}, pmid = {1459729}, issn = {0020-7136}, mesh = {Animals ; Asbestos ; Cell Division ; Disease Models, Animal ; Female ; Fluorescent Antibody Technique ; H-2 Antigens/analysis ; Mesothelioma/etiology/immunology/*pathology/ultrastructure ; Mice ; Mice, Inbred BALB C ; Mice, Inbred CBA ; Tumor Cells, Cultured ; }, abstract = {Malignant mesothelioma (MM) is an aggressive tumour of the serosal cavities which is associated with previous asbestos exposure and is generally found to be resistant to conventional forms of therapy. Adequate scientific and clinical assessment of this disease has been severely limited by the relatively low incidence of mesothelioma and the lack of representative cell lines and animal models. The purpose of this study was to develop an asbestos-induced murine model of MM both as an in vivo-passaged malignancy and as in vitro-established cell lines. Such a model system would be invaluable for use in the study of various cellular, molecular and genetic aspects of the disease, and for the pre-clinical evaluation of potential therapeutic agents. BALB/c and CBA mice were injected intraperitoneally with crocidolite asbestos. Seven to 25 months after exposure, 35% of the mice developed mesothelioma (5 BALB/c, 9 CBA), as determined by standard cytological and histological parameters. From these primary tumours, 12 continuously growing cell lines (5 BALB/c, 7 CBA) were established in culture. All have been confirmed as mesothelioma by cytological and ultrastructural (electron microscopy) analyses. These lines have been in culture for 7 to 24 months and have achieved passages above 32 (range 32 to 106). As in the human disease, the murine mesothelioma lines vary in their morphology and growth rates (doubling times ranging from 14 to 30 hr). All cell lines produced tumours when injected into syngeneic mice.}, } @article {pmid1472439, year = {1992}, author = {Al Jarad, N and Uthayakumar, S and Buckland, EJ and Green, TS and Ord, J and Newland, AC and Rudd, RM}, title = {The histocompatibility antigen in asbestos related disease.}, journal = {British journal of industrial medicine}, volume = {49}, number = {12}, pages = {826-831}, pmid = {1472439}, issn = {0007-1072}, mesh = {Adult ; Aged ; Antibodies, Antinuclear/analysis ; Asbestosis/*immunology ; Female ; Histocompatibility Antigens Class I/*analysis/genetics ; Histocompatibility Antigens Class II/*analysis/genetics ; Humans ; Male ; Middle Aged ; Rheumatoid Factor/analysis ; }, abstract = {Thirty nine phenotypes of human leucocyte antigens (HLA)-A-B-DR and DQ were obtained from 99 asbestos workers (one woman and 98 men). Presence or absence of antinuclear antibodies and rheumatoid factor was determined in 91 of them. Workers were divided into five groups: asbestos workers with no apparent disease (AW; n = 17), diffuse benign pleural disease (PD; n = 31), asbestosis (AS; n = 24), asbestosis with lung cancer (AS-CA; n = 14), and mesothelioma (M; n = 13). Compared with AW, several trends of differences of HLA antigen prevalence were found in patients with asbestos related disease, but these did not achieve statistical significance when p was corrected (pcorr) by number of analyses undertaken. Analysis of the results obtained in previous studies together with the results of this study showed that compared with AW, AS patients had decreased prevalence of HLA-DR5 (pcorr < 0.02). Reasons for the differences in results of previous studies and statistical methods commonly used to compare prevalences of HLA antigen are discussed.}, } @article {pmid1456576, year = {1992}, author = {Constantopoulos, SH and Dalavanga, YA and Sakellariou, K and Goudevenos, J and Kotoulas, OB}, title = {Lymphocytic alveolitis and pleural calcifications in nonoccupational asbestos exposure. Protection against neoplasia?.}, journal = {The American review of respiratory disease}, volume = {146}, number = {6}, pages = {1565-1570}, doi = {10.1164/ajrccm/146.6.1565}, pmid = {1456576}, issn = {0003-0805}, mesh = {Asbestos/*adverse effects ; Bronchoalveolar Lavage Fluid/pathology ; Bronchoscopy ; Calcinosis/diagnostic imaging/etiology/*pathology ; Environmental Exposure ; Female ; Humans ; Lung Neoplasms/*etiology/pathology ; Lymphocytes/*pathology ; Male ; Middle Aged ; Paint/adverse effects ; Pleural Diseases/diagnostic imaging/etiology/*pathology ; Pleural Neoplasms/*etiology ; Pulmonary Fibrosis/diagnostic imaging/*etiology/pathology ; Radiography ; }, abstract = {Inhabitants of the Metsovo area in Northwest Greece (population, 4,000) have been exposed to asbestos through the use of whitewash containing tremolite. This has resulted in endemic pleural calcifications (PCs) and increased incidence of malignant pleural mesothelioma (MPM). In order to evaluate the lung response to the fiber, bronchoalveolar lavage (BAL) was performed in 25 Metsovites; 14 with PCs, three with PCs and neoplasia, five without PCs, and three without PCs but with established neoplasia. There were no differences between the four groups with regard to age or exposure. Twelve Metsovites had lymphocytic alveolitis (BAL lymphocytes > 15%). Eleven belonged to the group with PCs and one belonged to the group without PCs. None of those with neoplasia had alveolitis. The lymphocytes were mainly helper T-cells, and activation markers were more frequent among those with PCs. We have previously reported on the relative absence of PCs in Metsovites with malignant pleural mesothelioma. This observation and the results of the present study suggest that lymphocytic alveolitis correlates with pleural calcifications, whereas both are rarely present in patients with neoplasia.}, } @article {pmid1288739, year = {1992}, author = {Hand, AM and Husgafvel-Pursiainen, K and Pelin, K and Vallas, M and Suitiala, T and Ekman, A and Mattson, M and Mattson, K and Linnainmaa, K}, title = {Interferon-alpha and -gamma in combination with chemotherapeutic drugs: in vitro sensitivity studies in four human mesothelioma cell lines.}, journal = {Anti-cancer drugs}, volume = {3}, number = {6}, pages = {687-694}, doi = {10.1097/00001813-199212000-00020}, pmid = {1288739}, issn = {0959-4973}, mesh = {Antineoplastic Agents/*pharmacology ; Cell Survival/drug effects ; Cisplatin/pharmacology ; DNA, Neoplasm/drug effects/metabolism ; Drug Screening Assays, Antitumor ; Female ; Humans ; Interferon Type I/*pharmacology ; Interferon-gamma/*pharmacology ; Mesothelioma/*pathology ; Pregnancy ; Recombinant Proteins ; Tumor Cells, Cultured/drug effects ; }, abstract = {Mesothelioma is a tumor of the serous surfaces in the thorax and abdomen. This tumor has proved to be exceptionally resistant to treatment, although a variety of multi-modality therapies have been tried. We have used four human mesothelioma cell lines, originating from diffuse asbestos-related malignant (pleural) mesothelioma, to assess in vitro sensitivity to five chemotherapeutic drugs, to recombinant human interferon (IFN)-alpha and -gamma and to combined immuno-chemotherapy. The cytotoxic effects were assayed by vital dye exclusion. The drugs tested were etoposide, cisplatin, mitoxantrone, 4-epirubicin and vindesine. The combinations tested were etoposide+cisplatin, and etoposide+cisplatin+mitoxantrone. All the drugs and combinations were also tested with recombinant human (rHu) IFN-alpha 2C (rHuIFN-alpha), rHuIFN-gamma, and rHuIFN-alpha+rHuIFN-gamma. The cell lines were most sensitive to mitoxantrone, 4-epirubicin and vindesine (TC50 < or = 0.001 micrograms/ml), and least sensitive to etoposide and cisplatin (TC50 > or = 0.1 micrograms/ml) used singly. There was no improvement in sensitivity when the drugs were combined. To further investigate the lack of response to cisplatin treatment, we examined the binding of cisplatin to the mesothelioma cell DNA. The tumor cell DNA bound markedly less cisplatin than human fetal fibroblast DNA. Three cell lines were tested with rHuIFN-alpha and rHuIFN-gamma on their own or rHuIFN-alpha+rHuIFN-gamma. They were consistently sensitive to rHuIFN-alpha, but the sensitivity to rHuIFN-gamma varied with the cell lines. Finally, we tested two cell lines with the drugs singly and in combination, together with 0.01 micrograms/ml each of rHuIFN-alpha and rHuIFN-gamma.(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid1462468, year = {1992}, author = {Jensen, BN and Viskum, K}, title = {[Primary malignant pleural neoplasms. Diagnostic code 163.09].}, journal = {Ugeskrift for laeger}, volume = {154}, number = {49}, pages = {3504-3506}, pmid = {1462468}, issn = {0041-5782}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Female ; Humans ; Male ; Mesothelioma/*diagnosis/etiology/pathology ; Middle Aged ; Occupational Diseases/diagnosis/etiology/pathology ; Pleural Neoplasms/*diagnosis/etiology/pathology ; }, abstract = {The code 163.09 indicates a primary malignant pleural neoplasma-malignant mesothelioma. We have reinvestigated 173 patients, who were discharged from a department of pulmonary medicine with this code number during a 8 1/2 year period. A revision during which repeated biopsies, course of the disease and, in some cases, autopsy were considered, revealed that 63 were confirmed as having a malignant mesothelioma, 94 had neoplastic disease secondary to malignancy elsewhere, 13 had benign changes and in three cases the records were missing. Malignant mesothelioma entitles the patient to compensation if he has worked with asbestos. An occupational history was present in 94% of those suffering from mesothelioma and in 71% of the remaining patients. Among patients with mesothelioma a history of asbestos exposure was obtained in 44%, a history of no exposure in 22% and no specific mention of asbestos in 34%. In the group of patients who did not have mesothelioma 14% had known exposure to asbestos, eight none and in 78% no specific information concerning asbestos was available. Twenty-three of the 63 patients with mesothelioma had been notified to the workmens' compensation board. Retrospectively, we found that 12 more patients should have been notified. Eight patients who did not fulfil the criteria for malignant mesothelioma had erroneously been notified to the board for compensation. We find that code 163.09 frequently has been used as a working diagnosis, which could not invariably be substantiated. Although malignant mesothelioma had been suspected, previous history concerning asbestos exposure was often incomplete or absent. A correct occupational history and aggressive bioptical procedures are essential in all cases where malignant mesothelioma is suspected.(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid1414807, year = {1992}, author = {Patz, EF and Shaffer, K and Piwnica-Worms, DR and Jochelson, M and Sarin, M and Sugarbaker, DJ and Pugatch, RD}, title = {Malignant pleural mesothelioma: value of CT and MR imaging in predicting resectability.}, journal = {AJR. American journal of roentgenology}, volume = {159}, number = {5}, pages = {961-966}, doi = {10.2214/ajr.159.5.1414807}, pmid = {1414807}, issn = {0361-803X}, mesh = {Asbestos/adverse effects ; Environmental Exposure ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Mesothelioma/*diagnosis/epidemiology/surgery ; Middle Aged ; Pleural Neoplasms/*diagnosis/epidemiology/surgery ; Pneumonectomy ; Predictive Value of Tests ; Sensitivity and Specificity ; Tomography, X-Ray Computed ; }, abstract = {OBJECTIVE: Our objective was to determine if CT or MR imaging findings could be used to accurately predict resectability in patients with biopsy-proved malignant pleural mesotheliomas.

SUBJECTS AND METHODS: CT and MR findings in 41 consecutive patients with malignant mesotheliomas who were referred to the thoracic surgery clinic for extrapleural pneumonectomy were studied by thoracic radiologists before surgery. Review of radiologic studies focused on local invasion of three separate regions: the diaphragm, chest wall, and mediastinum. Results of all imaging examinations were carefully correlated with intraoperative, gross, and microscopic pathologic findings.

RESULTS: After radiologic and clinical evaluation, 34 patients (83%) had thoracotomy; 24 of these had tumors that were resectable. The sensitivity was high (> 90%) for both CT and MR in each region. Specificity, however, was low, probably because of the small number of patients with unresectable tumors.

CONCLUSION: CT and MR provided similar information on resectability in most cases. Sensitivity was high for both procedures. Because CT is more widely available and used, we suggest it as the initial study when determining resectability. In difficult cases, important complementary anatomic information can be derived from MR images obtained before surgical intervention.}, } @article {pmid1484440, year = {1992}, author = {Kishimoto, T and Sato, T}, title = {[Two cases of malignant mesothelioma controlled by pleurectomy].}, journal = {Nihon Kyobu Shikkan Gakkai zasshi}, volume = {30}, number = {11}, pages = {1996-2001}, pmid = {1484440}, issn = {0301-1542}, mesh = {Aged ; Asbestos/adverse effects ; Biopsy ; Humans ; Male ; Mesothelioma/etiology/pathology/*surgery ; Middle Aged ; Occupational Exposure ; Pleura/pathology/*surgery ; Pleural Effusion, Malignant/pathology/surgery ; Pleural Neoplasms/etiology/pathology/*surgery ; }, abstract = {Open biopsy and pleurectomy were performed in 2 cases of asbestos exposure with bloody pleural effusion. Pathological examination revealed marked proliferation of fibrous tissue containing tumor cells. The tumor was diagnosed as malignant pleural mesothelioma on the basis of histochemical staining and transmission electron microscopy. Almost complete excision of tumor tissue was performed, and malignant mesothelioma had not relapsed 10 and 12 months after the operation. We recommend open biopsy and pleurectomy for cases of exposure with bloody and intractable pleural effusion.}, } @article {pmid1410312, year = {1992}, author = {Wechsler, RJ and Steiner, RM and Conant, EF}, title = {Occupationally induced neoplasms of the lung and pleura.}, journal = {Radiologic clinics of North America}, volume = {30}, number = {6}, pages = {1245-1268}, pmid = {1410312}, issn = {0033-8389}, mesh = {Humans ; Lung/diagnostic imaging ; Lung Neoplasms/diagnostic imaging/*etiology ; Mesothelioma/diagnostic imaging/etiology ; *Occupational Diseases/diagnostic imaging ; Pleura/diagnostic imaging ; Pleural Neoplasms/diagnostic imaging/*etiology ; Radiography ; }, abstract = {The relationship between asbestos and mesothelioma has been well delineated in the past. The epidemiologic, clinical, radiologic, and pathologic features of mesothelioma are discussed with reference to the diagnostic evaluation of asbestos-exposed patients. The extensive epidemiologic data correlating asbestos, tobacco smoke, and induction of lung carcinoma are also reviewed. These data provide a model for evaluation of other occupationally induced lung carcinogens such as organic and metallic industrial inhalants.}, } @article {pmid1410307, year = {1992}, author = {McLoud, TC}, title = {Conventional radiography in the diagnosis of asbestos-related disease.}, journal = {Radiologic clinics of North America}, volume = {30}, number = {6}, pages = {1177-1189}, pmid = {1410307}, issn = {0033-8389}, mesh = {Asbestos/*adverse effects ; Asbestosis/*diagnostic imaging ; Carcinoma, Bronchogenic/diagnostic imaging/etiology ; Humans ; Lung/diagnostic imaging ; Lung Neoplasms/*diagnostic imaging/etiology ; Mesothelioma/diagnostic imaging/etiology ; Occupational Diseases/*diagnostic imaging/etiology ; Pleura/diagnostic imaging ; Radiography ; }, abstract = {Standard chest radiography, despite its limitations, remains an important means of evaluating the asbestos-exposed worker. Because of its wide availability, low radiation dose, and low cost, it will continue to be the standard imaging procedure for the screening of asbestos-exposed populations.}, } @article {pmid1361144, year = {1992}, author = {Carthew, P and Hill, RJ and Edwards, RE and Lee, PN}, title = {Intrapleural administration of fibres induces mesothelioma in rats in the same relative order of hazard as occurs in man after exposure.}, journal = {Human & experimental toxicology}, volume = {11}, number = {6}, pages = {530-534}, doi = {10.1177/096032719201100615}, pmid = {1361144}, issn = {0960-3271}, mesh = {Animals ; Asbestos/administration & dosage/*toxicity ; Carcinogens/administration & dosage/*toxicity ; Dose-Response Relationship, Drug ; Female ; Injections, Intraperitoneal ; Male ; Mesothelioma/*etiology ; Rats ; Rats, Wistar ; }, abstract = {1. The dose-response data for the induction of mesothelioma, in rats, by the intrapleural administration of the fibrous zeolite, erionite, has been compared to the published data for the crocidolite and chrysotile forms of asbestos. Erionite is more than two orders of magnitude more carcinogenic than either of the two forms of asbestos examined. 2. The relative sensitivity of the intrapleural and intraperitoneal routes of injection were also examined. The sensitivity of the intraperitoneal over the intrapleural route of administration was considerably greater for all the forms of asbestos examined but not for erionite. 3. The relationship for different fibres, between the number of fibres required to give animals mesothelioma, at the 50% or 10% observable tumour effect level (OTEL) was examined, and a ranking of relative carcinogenicity was made. 4. This showed that the data derived from the dose responses obtained by the intrapleural administration of fibres to rats ranked the relative carcinogenicity of erionite, crocidolite and chrysotile in accord with the known clinical mesothelioma induction in man after exposure to these fibres. Examination of the carcinogenicity ranking from data derived from intraperitoneal injections of fibres was not in accord with the known clinical mesothelioma induction in man for the various asbestos types examined.}, } @article {pmid1330349, year = {1992}, author = {Maples, KR and Johnson, NF}, title = {Fiber-induced hydroxyl radical formation: correlation with mesothelioma induction in rats and humans.}, journal = {Carcinogenesis}, volume = {13}, number = {11}, pages = {2035-2039}, doi = {10.1093/carcin/13.11.2035}, pmid = {1330349}, issn = {0143-3334}, mesh = {Aluminum Silicates/toxicity ; Animals ; Asbestos/*toxicity ; Chromatography, High Pressure Liquid ; Electrochemistry ; Glass ; Humans ; Hydrogen Peroxide/metabolism ; Hydroxides/*metabolism ; Hydroxyl Radical ; Mesothelioma/*etiology ; Rats ; Wool ; Zeolites ; }, abstract = {As part of a program to study the effects of inhaled fibers, we characterized the capacity of various fibers to initiate hydroxyl radical (.OH) formation from hydrogen peroxide in a non-cellular system. We studied five natural fibers (erionite, crocidolite, amosite, anthophyllite and chrysotile) and two man-made fibers (JM code 100 glass fibers and glass wool). The fibers were incubated for 5 min at 37 degrees C with hydrogen peroxide and salicylic acid in pH 7.0 aqueous solutions. The salicylate reacted with any .OH formed in these mixtures to produce stable addition products. The amount of .OH addition products formed during the incubations was determined by the salicylate assay which uses HPLC with electrochemical detection. Erionite, JM code 100 and glass wool were the most effective initiators of .OH formation, followed, in order, by crocidolite, amosite and chrysotile. When the capacity of the natural fibers to initiate .OH formation was plotted versus either the values for tumor rates of rats that received pleural inoculations of fibers or the literature values for the human mesothelioma mortality rates, positive correlations (r2 > or = 0.896) were found. Similar correlations with man-made fibers were not found. No positive correlation could be made between .OH formation capacity versus the tumor rates of rats that received peritoneal injections of either type of fibers.}, } @article {pmid1305384, year = {1992}, author = {Pontone, P and Crescenzi, A and el Osta, K and Petruzziello, L and Petruzziello, F and de Anna, L and La Torre, F}, title = {[Malignant peritoneal mesothelioma: apropos a new case].}, journal = {Annali italiani di chirurgia}, volume = {63}, number = {6}, pages = {807-10; discussion 810-1}, pmid = {1305384}, issn = {0003-469X}, mesh = {Adult ; Humans ; Lymph Nodes/pathology ; Male ; Mesothelioma/*pathology/surgery ; Omentum/pathology ; Peritoneal Neoplasms/*pathology/surgery ; }, abstract = {Prognosis for patients with malignant peritoneal mesothelioma is very poor, and most patients are beyond cure by the time the diagnosis has been made. The pathogenesis of this uncommon neoplasm seems to be related to asbestos and radiation exposure. The authors report a case of diffuse peritoneal mesothelioma in a 33-year-old man. Since the patient complained of aspecific symptoms and both biochemical and "imaging" studies did not provide useful informations for a definitive diagnosis, an exploratory laparotomy was performed. Intraoperative histological findings demonstrated the presence of a malignant peritoneal mesothelioma which had spread all over the omentum; considering the inoperability assessment of this case, the operation was completed and the patient was dismissed with an adjuvant chemo-therapy. Five weeks later the patient died.}, } @article {pmid1281957, year = {1992}, author = {Suzuki, Y}, title = {Diagnostic criteria for human diffuse malignant mesothelioma.}, journal = {Acta pathologica japonica}, volume = {42}, number = {11}, pages = {767-786}, doi = {10.1111/j.1440-1827.1992.tb01878.x}, pmid = {1281957}, issn = {0001-6632}, support = {ES 978/ES/NIEHS NIH HHS/United States ; }, mesh = {Carcinoembryonic Antigen/analysis ; Humans ; Hyaluronic Acid/*analysis ; Immunohistochemistry ; Keratins/analysis ; Membrane Glycoproteins/analysis ; Mesothelioma/*chemistry/*pathology/ultrastructure ; Microscopy, Electron ; Mucin-1 ; Mucins/*analysis ; Peritoneal Neoplasms/*chemistry/*pathology/ultrastructure ; Pleural Neoplasms/*chemistry/*pathology/ultrastructure ; }, abstract = {Diffuse malignant mesothelioma is a rare tumor in the general population, yet is unique in that it is caused almost exclusively by exposure to asbestos with long-term latency (15 years and over). Pathologists are required to provide a reliable diagnosis of the tumor for clinicians who are responsible for the treatment of affected patients. Pathological diagnosis of diffuse malignant mesothelioma is not always easy; however, it has improved over the last few decades. Currently, comprehensive analysis, including gross appearance, histology, histochemistry, immunocytochemistry and electron microscopy is recommended as the best approach to an accurate diagnosis of diffuse malignant mesothelioma.}, } @article {pmid1464547, year = {1992}, author = {Biermann, CW and Gasser, TC and Rutishauser, G}, title = {[Malignant mesothelioma of the tunica vaginalis testis].}, journal = {Helvetica chirurgica acta}, volume = {59}, number = {3}, pages = {501-502}, pmid = {1464547}, issn = {0018-0181}, mesh = {Aged ; Aged, 80 and over ; Humans ; Male ; Mesothelioma/pathology/*surgery ; Postoperative Complications/pathology/surgery ; Reoperation ; Testicular Hydrocele/pathology/surgery ; Testicular Neoplasms/pathology/*surgery ; Testis/pathology ; }, abstract = {Malignant mesothelioma of the tunica vaginalis testis is an extremely rare tumor, with only 37 cases previously described in the literature. Treatment consists of inguinal orchiectomy with close follow-up [1]. Asbestos exposure, trauma and hydrocele have been implicated as risk factors. We describe a patient's history and the pathological findings as well as the management according to preceding reports in the literature.}, } @article {pmid1426229, year = {1992}, author = {Giersiepen, K and Rösler, J and Woitowitz, HJ}, title = {Risk of lung cancer and mesothelioma after cessation of asbestos exposure.}, journal = {The European respiratory journal}, volume = {5}, number = {9}, pages = {1161-1162}, pmid = {1426229}, issn = {0903-1936}, mesh = {Asbestos/*adverse effects ; Cohort Studies ; Humans ; Lung Neoplasms/*epidemiology/etiology ; Male ; Mesothelioma/*epidemiology/etiology ; Occupational Diseases/*epidemiology/etiology ; Occupational Exposure ; Pleural Neoplasms/*epidemiology/etiology ; Sweden/epidemiology ; Time Factors ; }, } @article {pmid1419863, year = {1992}, author = {Ribak, J and Selikoff, IJ}, title = {Survival of asbestos insulation workers with mesothelioma.}, journal = {British journal of industrial medicine}, volume = {49}, number = {10}, pages = {732-735}, pmid = {1419863}, issn = {0007-1072}, mesh = {Age Factors ; Aged ; Asbestos/*adverse effects ; Humans ; Mesothelioma/*mortality ; Middle Aged ; Occupational Diseases/*mortality ; Occupational Exposure ; Peritoneal Neoplasms/*mortality ; Pleural Neoplasms/*mortality ; Prospective Studies ; Risk Factors ; Time Factors ; United States/epidemiology ; }, abstract = {Malignant mesothelioma is a lethal disease. It is rare in the general population; however, workers exposed to asbestos suffer significant burdens of the neoplasm. The survival time of 457 consecutive fatal cases of pleural and peritoneal mesothelioma that occurred among 17,800 asbestos insulation workers observed prospectively from 1 January 1967 to 1 January 1987 was studied. Mean survival time from initial presentation of the disease to death was 11.4 months for the pleural mesothelioma patients compared with 7.4 months for the peritoneal group. This difference was statistically significant. Mean survival time from diagnosis to death was shorter for both groups of patients: 8.4 months for pleural mesothelioma v 5.8 months for the peritoneal cases. In conclusion, survival time in mesothelioma patients is short; most die within a year from the onset of the initial symptoms. No effective therapy is yet available.}, } @article {pmid1395779, year = {1992}, author = {Turner, JF and Gronbeck, C and Stacy, C}, title = {Solitary pulmonary nodule in a patient without asbestos exposure.}, journal = {Chest}, volume = {102}, number = {4}, pages = {1267-1268}, doi = {10.1378/chest.102.4.1267}, pmid = {1395779}, issn = {0012-3692}, mesh = {Aged ; Female ; Humans ; Lung Neoplasms/*diagnostic imaging ; Mesothelioma/*diagnostic imaging ; Radiography ; Solitary Pulmonary Nodule/*diagnostic imaging ; }, } @article {pmid1515995, year = {1992}, author = {Dawson, A and Gibbs, A and Browne, K and Pooley, F and Griffiths, M}, title = {Familial mesothelioma. Details of 17 cases with histopathologic findings and mineral analysis.}, journal = {Cancer}, volume = {70}, number = {5}, pages = {1183-1187}, doi = {10.1002/1097-0142(19920901)70:5<1183::aid-cncr2820700526>3.0.co;2-o}, pmid = {1515995}, issn = {0008-543X}, mesh = {Aged ; Asbestos/adverse effects/analysis/pharmacokinetics ; Body Burden ; Family Health ; Female ; Humans ; Lung/chemistry/metabolism ; Lung Neoplasms/etiology/*genetics/pathology ; Male ; Mesothelioma/etiology/*genetics/pathology ; Microscopy, Electron ; Middle Aged ; Minerals/*analysis ; }, abstract = {Nine new cases of mesothelioma clustering in four families are described, and additional information is provided on four previously reported families. All of the members of these families had some exposure to asbestos. Diagnoses were confirmed histologically, and the relevance of the histologic pattern is discussed after the literature review. The lung mineral fiber burden was quantified in patients by transmission electron microscopic examination and energy-dispersive x-ray analysis, and this confirmed significant exposure to amphibole asbestos in all patients. Evidence supporting an increased incidence of mesothelioma in family members is discussed.}, } @article {pmid1470029, year = {1992}, author = {Athanasiou, K and Constantopoulos, SH and Rivedal, E and Fitzgerald, DJ and Yamasaki, H}, title = {Metsovo-tremolite asbestos fibres: in vitro effects on mutation, chromosome aberration, cell transformation and intercellular communication.}, journal = {Mutagenesis}, volume = {7}, number = {5}, pages = {343-347}, doi = {10.1093/mutage/7.5.343}, pmid = {1470029}, issn = {0267-8357}, support = {R01 CA40534/CA/NCI NIH HHS/United States ; }, mesh = {Aneuploidy ; Animals ; Asbestos/adverse effects/pharmacology/*toxicity ; *Asbestos, Amphibole ; Cell Communication/*drug effects ; Cell Line ; Cell Transformation, Neoplastic/*chemically induced ; *Chromosome Aberrations ; Cricetinae ; Cricetulus ; Greece ; Humans ; Incidence ; Mesocricetus ; Mesothelioma/epidemiology/etiology ; Micronucleus Tests ; *Mutagenesis ; Mutagenicity Tests ; Pleural Neoplasms/epidemiology/etiology ; Salmonella typhimurium/drug effects ; Silicic Acid/adverse effects/pharmacology/*toxicity ; }, abstract = {Samples of Metsovo-tremolite asbestos, previously found to be the causative agent of endemic pleural calcification and an increased level of malignant pleural mesothelioma in a rural area of north-western Greece (Metsovo area), were tested in various in vitro toxicity test systems. It was found that asbestos fibres of this type were strong inducers of micronuclei and numerical chromosomal abnormalities while they induced low levels of chromosomal aberrations in mammalian cells in culture. Furthermore, this type of asbestos can induce a low level of in vitro transformation of Syrian hamster embryo cells. The fibres had no effect on gap-junctional cell-cell communication (followed by the dye-transfer method) and did not induce any mutations in the Salmonella typhimurium strain TA102 which is known to be sensitive to the action of various oxidative agents. These results support the hypothesis generated from studies on other types of asbestos that such fibres induce tumours by causing chromosomal mutations.}, } @article {pmid1464814, year = {1992}, author = {Zalay, Z and Nemeth, L and Sugar, J}, title = {Screening and pathological diagnosis of asbestosis and mesothelioma: a review.}, journal = {Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer}, volume = {11}, number = {5-6}, pages = {317-321}, pmid = {1464814}, issn = {0731-8898}, mesh = {Asbestosis/complications/epidemiology/*pathology ; Biomarkers, Tumor/analysis ; Carcinoembryonic Antigen/analysis ; Chromosome Aberrations/diagnosis ; Chromosome Disorders ; Humans ; Hungary/epidemiology ; Mass Screening/*methods ; Mesothelioma/epidemiology/etiology/genetics/*pathology ; }, abstract = {X-ray screenings of workers employed in asbestos manufacturing in Hungary revealed 255 cases of asbestosis and 3 cases of malignant mesothelioma. The pathological diagnosis of asbestosis is not very difficult. The diagnosis of mesothelioma, however, is fraught with problems. To identify mesothelioma we use histochemical reactions with PAS diastase digestion and immunohistochemical reactions for cytokeratin, vimentin, and CEA. The PAS and CEA reactions are negative but the vimentin and cytokeratin are positive in mesothelioma. Cytogenetic and molecular genetic studies may contribute to the better understanding of the pathogenesis and, thus, open new perspectives in our understanding of mesotheliomas.}, } @article {pmid1464811, year = {1992}, author = {Moran, EM}, title = {Epidemiological factors of cancer in California.}, journal = {Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer}, volume = {11}, number = {5-6}, pages = {303-307}, pmid = {1464811}, issn = {0731-8898}, mesh = {Acquired Immunodeficiency Syndrome/complications ; Air Pollution/adverse effects ; Asbestos ; Asia/ethnology ; Black People ; California/epidemiology ; Female ; Hispanic or Latino ; Humans ; Life Style ; Male ; Neoplasms/*ethnology/etiology ; Occupations ; Water Supply ; White People ; Black or African American ; }, abstract = {California has 12% of the U.S. population. In 1991, the newly diagnosed cancer cases in California represented 10% of all new cancer cases in the country, and the yearly toll was 10% of all cancer deaths. Relative to all new cancer cases in the U.S., California had 10, 9.8, 9.8, and 9.3% of breast, lung, prostate, and colorectal cancers, respectively. Because of its large population and cancer incidence, the epidemiology of cancer in California is of particular interest. Epidemiological factors reviewed in this article include ethnicity, lifestyle, occupation, and environmental conditions. Ethnic factors: There is an increased incidence of cervical and gallbladder cancer among Hispanic women, and of stomach cancer in Hispanic men and women. In U.S.-born Chinese men, the most prevalent cancers are those of the lung and colon, which is also seen in American white men. In U.S.-born Chinese women, there is an upward displacement of breast cancer incidence. In U.S.-born Japanese men and women, the mortality rate is closer to that of American whites. Life-style: Members of the Mormon Church and Seventh-Day Adventists have only 50% of the U.S. standardized mortality rate for cancer associated with smoking. Increased coffee consumption has been found to be associated with increased occurrence of colon and bladder cancer; alcohol use has been reported to have a positive association with colorectal cancer. The large AIDS population in San Francisco has a 144-fold odds ratio of Kaposi's sarcoma and a fivefold odds ratio of lymphoma when compared with the general U.S. population. Occupational factors: An increased incidence of mesothelioma in asbestos workers, of gastric cancer, skin cancer, and lymphoma in men working in dusty environments, and of astrocytoma in individuals with prolonged exposure to low-frequency electric and magnetic fields has been recorded. Environmental factors: The drinking-water pool in northern California is contaminated with asbestos of the serpentine type, which is associated with mesothelioma of the peritoneum and carcinoma of the lung, gallbladder, and pancreas. Petrochemical fumes in the heavily industrialized San Francisco Bay area have not been associated with an increased occurrence of cancer. No significant incidence in cancer has been noted in the counties surrounding the nuclear power plant at San Onofre during 18 years of close observation.}, } @article {pmid1325339, year = {1992}, author = {Selçuk, ZT and Cöplü, L and Emri, S and Kalyoncu, AF and Sahin, AA and Bariş, YI}, title = {Malignant pleural mesothelioma due to environmental mineral fiber exposure in Turkey. Analysis of 135 cases.}, journal = {Chest}, volume = {102}, number = {3}, pages = {790-796}, doi = {10.1378/chest.102.3.790}, pmid = {1325339}, issn = {0012-3692}, mesh = {Actuarial Analysis ; Aluminum Silicates/*adverse effects ; Asbestos/*adverse effects ; Environmental Exposure ; Female ; Humans ; Male ; Mesothelioma/diagnosis/*etiology/mortality ; Middle Aged ; Pleural Neoplasms/diagnosis/*etiology/mortality ; Prognosis ; Sex Factors ; Turkey/epidemiology ; Zeolites ; }, abstract = {We reviewed data from 135 patients with environment-associated malignant pleural mesothelioma (MPM) from the Central Anatolian region of Turkey. The most significant factors suggesting the diagnosis of MPM were the village where the patient resided and the typical presenting symptoms and signs of unilateral exudative pleural effusion associated with nonpleuritic chest pain. Computed tomography and ultrasonography were very useful for evaluating the extension of the tumor in the thoracic and abdominal cavities and chest wall. The tissue diagnosis was established by either thoracoscopy (39 percent) or pleural biopsy (39 percent) in the majority of the cases. The median survival after diagnosis was 13.52 months for erionite-associated MPM and 21.56 months for asbestos-associated MPM. The actuarial survival curves for the fibrous minerals were significantly different for survival computed both from onset of the symptoms and after diagnosis. Medical or surgical treatment or both did not change the outcome of the disease.}, } @article {pmid1515354, year = {1992}, author = {Cazzadori, A and Malesani, F and Romeo, L}, title = {Malignant pleural mesothelioma caused by non-occupational childhood exposure to asbestos.}, journal = {British journal of industrial medicine}, volume = {49}, number = {8}, pages = {599}, pmid = {1515354}, issn = {0007-1072}, mesh = {Adult ; Asbestos/*adverse effects ; *Environmental Exposure ; Female ; Humans ; Mesothelioma/*etiology ; Pleural Neoplasms/*etiology ; }, } @article {pmid1509283, year = {1992}, author = {Vogelzang, NJ}, title = {Malignant mesothelioma: diagnostic and management strategies for 1992.}, journal = {Seminars in oncology}, volume = {19}, number = {4 Suppl 11}, pages = {64-71}, pmid = {1509283}, issn = {0093-7754}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Mesothelioma/diagnosis/pathology/*therapy ; Middle Aged ; }, abstract = {Malignant mesothelioma of the pleural and peritoneal surfaces is epidemiologically linked to crocidolite, a long, thin, and rigid form of asbestos whose use has been dramatically curtailed within the past 20 to 25 years. The incidence of disease may have peaked around 1984 and may now be declining. The highest incidence of disease occurs in elderly white men (greater than or equal to 75 years old). The histology of mesothelioma is classically biphasic, with both epithelioid and sarcomatous areas present. Independent pathologic review can be useful, and a variety of special stains should be used, if diagnosis is unclear. Electron microscopy and serum carcinoembryonic antigen levels are also useful. Surgical treatments have been difficult, but 3-year survival rates range from 15% to 36%. Unfortunately, only about 20% of all diagnosed patients are candidates for aggressive surgical approaches. Radiotherapy likewise has been disappointing, although occasionally useful. Lastly, 13 single-agent chemotherapy trials conducted on 302 patients using 10 different commercially available drugs have failed to identify a consistently effective agent. Combination chemotherapy has also not proven effective and, therefore innovative new approaches are needed.}, } @article {pmid1428808, year = {1992}, author = {Tulchinsky, TH and Ginsberg, GM and Shihab, S and Goldberg, E and Laster, R}, title = {Mesothelioma mortality among former asbestos-cement workers in Israel, 1953-90.}, journal = {Israel journal of medical sciences}, volume = {28}, number = {8-9}, pages = {543-547}, pmid = {1428808}, issn = {0021-2180}, mesh = {Adolescent ; Adult ; Asbestos/*adverse effects ; Cohort Studies ; Humans ; Israel/epidemiology ; Male ; Mesothelioma/etiology/*mortality ; Middle Aged ; Occupational Diseases/etiology/*mortality ; }, abstract = {Asbestos workers have long been recognized as a high risk group for the development of mesothelioma and other cancers. In this study we collated from a variety of sources 26 mesothelioma deaths that occurred between 1978 and 1990 among a cohort of some 4,441 former workers from an asbestos-cement plant in northern Israel. Since the expected number of deaths for this number of Israeli males in this age-group over this period is 0.12 cases, the risk of this disease was more than 223 times the national rate, age and sex adjusted [standardized mortality ratio (SMR) = 22,351, P < 0.001]. The mean years of exposure of persons who died from mesothelioma was 16.2 (SE 2.5). The mean latency period for mesothelioma cases from onset of exposure to death was 25.6 years (SE 1.3). Additional follow-up systems are needed to ensure complete reporting of asbestos-related diseases, including epidemiologic follow-up of asbestos-exposed workers after cessation of their work, with regular analysis of death and cancer registry data for high risk groups. Asbestos-related cancer is an important element in cancer epidemiology that requires further development in Israel. Studies of former workers, their families and of persons who worked or attended school adjacent to the asbestos-cement factory, as well as follow-up of other former worker groups exposed to asbestos are recommended.}, } @article {pmid1325180, year = {1992}, author = {Sluis-Cremer, GK and Liddell, FD and Logan, WP and Bezuidenhout, BN}, title = {The mortality of amphibole miners in South Africa, 1946-80.}, journal = {British journal of industrial medicine}, volume = {49}, number = {8}, pages = {566-575}, pmid = {1325180}, issn = {0007-1072}, mesh = {Asbestos/*adverse effects ; Asbestos, Amosite ; Asbestos, Crocidolite ; Cause of Death ; Cohort Studies ; Humans ; Incidence ; Lung Neoplasms/mortality ; Male ; Mesothelioma/mortality ; *Mining ; Neoplasms/mortality ; Occupational Diseases/*mortality ; Risk Factors ; South Africa/epidemiology ; Survival Analysis ; }, abstract = {A cohort was established in 1981 of all 7317 white male employees in the amosite and crocidolite mines in South Africa whose names had appeared in the personnel records (initiated between 1945 and 1955) of the major companies. Some of the men had been employed as early as 1925, but only 8% had had more than 10 years of service. Three subcohorts were defined: 3212 men whose only exposure to asbestos was to amosite; 3430 exposed to crocidolite; and 675 to both amphiboles. No deaths or losses to view occurred before 1946, and 5925 men (81%) were known to be alive at the end of 1980. Losses to view numbered 167 (2%), and there had been 1225 deaths (17%), an excess of 331 over the number of deaths expected on the basis of the mortality of all white South African males. The fibre related excesses were of mesothelioma, lung cancer, and other respiratory diseases, but there were other excesses perhaps mainly related to socioeconomic factors including lifestyle. When cause of death was determined according to "best evidence" (after study of clinical, radiological, biopsy, and necropsy reports in conjunction with the death certificate), there were 30 deaths due to mesothelioma (22 pleural, six peritoneal, two other) and 65 due to cancer of trachea, bronchus, and lung. Various analyses of these deaths showed that crocidolite had higher toxicity than amosite for lung cancer and this was most pronounced for mesothelioma; there can now be no question that crocidolite is far more dangerous than amosite at least in so far as mesothelioma is concerned. Nevertheless, crocidolite induced mesothelioma appeared only in men who had been exposed for long periods, at least 12 months, but on average about 15 years.}, } @article {pmid1323425, year = {1992}, author = {Gabrielson, EW and Van der Meeren, A and Reddel, RR and Reddel, H and Gerwin, BI and Harris, CC}, title = {Human mesothelioma cells and asbestos-exposed mesothelial cells are selectively resistant to amosite toxicity: a possible mechanism for tumor promotion by asbestos.}, journal = {Carcinogenesis}, volume = {13}, number = {8}, pages = {1359-1363}, doi = {10.1093/carcin/13.8.1359}, pmid = {1323425}, issn = {0143-3334}, mesh = {Asbestos/*toxicity ; Asbestos, Amosite ; Cells, Cultured ; Colony-Forming Units Assay ; DNA Replication/drug effects ; Dose-Response Relationship, Drug ; Epithelium/drug effects ; Humans ; Hydrogen Peroxide/toxicity ; Lethal Dose 50 ; Lung Neoplasms/*chemically induced/pathology ; Mesothelioma/*chemically induced/pathology ; Silicon Dioxide/toxicity ; Tumor Cells, Cultured ; }, abstract = {To determine if asbestos exposure could contribute to mesothelial cell carcinogenesis by selection and/or expansion of an initiated cell population, we compared normal human pleural mesothelial cells to either human mesothelioma cell lines or mesothelial cells transfected with cancer-related genes for sensitivity to amosite fibers in vitro. Neither normal nor mesothelioma cells were directly stimulated to replicate or increase DNA synthesis by any of the asbestos exposure conditions tested. The potential selective effect of asbestos exposure was demonstrated by a differential sensitivity of normal mesothelial cells and mesothelioma cells to amosite: for example, up to 20-fold higher concentrations of amosite fibers were required to inhibit replication of mesothelioma cell lines than normal mesothelial cells. In addition, a significant resistance (4-fold) to amosite toxicity was observed for SV40 immortalized mesothelial cell lines that had previously been selected in vitro for resistance to asbestos. SV40 immortalized cells that have become tumorigenic after transfection with either Ha-ras or PDGF A-chain genes were not significantly more resistant to the cytotoxic effects of amosite than primary normal cells, and the primary cells were equally sensitive to amosite as mesothelial cells that were only immortalized by SV40. The sensitivity of normal mesothelial cells to asbestos does not appear to be simply a result of general fragility of the mesothelial cells, since similar levels of hydrogen peroxide and silica were cytotoxic for normal mesothelial cells and mesothelioma cell lines. Because mesothelioma cells have a greater resistance to asbestos cytotoxicity than normal mesothelial cells, we hypothesize that a differential resistance to cell killing by asbestos fibers in vivo may result in a selective expansion of an initiated or transformed cell population and thus contribute to the carcinogenesis process. Since tumorigenicity and asbestos resistance occur independently of one another in genetically altered mesothelial cell lines, genotypic and phenotypic alterations that lead to tumorigenic conversion may not be the same changes that provide resistance to cell killing by asbestos.}, } @article {pmid1619688, year = {1992}, author = {Schneiderman, MA}, title = {Asbestos-related cancer.}, journal = {Journal of the National Cancer Institute}, volume = {84}, number = {14}, pages = {1125}, doi = {10.1093/jnci/84.14.1125}, pmid = {1619688}, issn = {0027-8874}, mesh = {Asbestos/*adverse effects ; Humans ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Neoplasms/*etiology ; Occupational Exposure ; Risk Factors ; }, } @article {pmid1461190, year = {1992}, author = {Sichletidis, L and Daskalopoulou, E and Tsarou, V and Pnevmatikos, I and Chloros, D and Vamvalis, C}, title = {Five cases of pleural mesothelioma with endemic pleural calcifications in a rural area in Greece.}, journal = {La Medicina del lavoro}, volume = {83}, number = {4}, pages = {326-329}, pmid = {1461190}, issn = {0025-7818}, mesh = {Aged ; Asbestos/*adverse effects ; Calcinosis/diagnostic imaging/*etiology ; Greece ; Humans ; Male ; Mesothelioma/diagnostic imaging/*etiology ; Middle Aged ; Pleural Diseases/diagnostic imaging/*etiology ; Pleural Neoplasms/diagnostic imaging/*etiology ; Radiography ; }, abstract = {The authors describe 5 cases of pleural mesothelioma in a rural population of Macedonia, Greece. This population had been covered by an X-ray study over a 3-year period to detect pleural calcifications compatible with asbestos exposure. The study revealed a 24.2% prevalence of pleural plaques among the inhabitants aged over 40 years of 7 rural villages. High contents of asbestos (chrysotile and tremolite)--up to 90% by volume--were found in the material that was used for whitewashing the houses up to 1935. Even now, environmental concentrations of 0.01 fibres/ml were recorded in the houses. The prevalence of pleural mesothelioma in this rural population is high compared to the general population. A possible explanation of the phenomenon may be a cumulative environmental exposure to asbestos which, even though presumably within the acceptable limits for occupational exposure, lasted over a much longer time period, in terms of both daily exposure and total duration.}, } @article {pmid1446251, year = {1992}, author = {Renier, A and Yegles, M and Buard, A and Dong, H and Kheuang, L and Saint-Etienne, L and Laurent, P and Jaurand, MC}, title = {Use of mesothelial cell cultures to assess the carcinogenic potency of mineral or man made fibers.}, journal = {Cell biology and toxicology}, volume = {8}, number = {3}, pages = {133-139}, pmid = {1446251}, issn = {0742-2091}, mesh = {Animals ; Asbestos/toxicity ; Carcinogenicity Tests ; Carcinogens/*toxicity ; Cells, Cultured ; Epithelium/drug effects ; Minerals/*toxicity ; Models, Biological ; }, abstract = {Natural mineral fibers may produce pulmonary cancers and mesothelioma. In contrast with lung cancer, the incidence of fiber-induced mesothelioma is not enhanced in smokers compared to non smokers. It is therefore of special interest to use mesothelial cells to study the toxicity of natural or man made mineral fibers. Several years ago, we have developed a method to culture rat pleural mesothelial cells (RPMC). We have first studied the effects of asbestos fibers by the application of in vitro tests formerly developed to determine the genotoxicity and transforming potency of soluble xenobiotics. Moreover, we have determined whether RPMC expressed cytochromes P450 known to metabolize polycyclic aromatic hydrocarbons. This paper reviews the results obtained so far. It has been found that asbestos fibers produced a cell transformation and a genotoxicity characterized by the formation of aneuploid cells, abnormal anaphases, chromosomal aberrations and DNA repair (UDS). In addition, RPMC expressed different forms of cytochromes P450. It is nowadays suggested that the tumorigenic potency of asbestos fibers may be related to the fiber dimensions, to their surface properties and in vivo biopersistence; this term involves the fiber solubility in biological medium and the fiber epuration from the lung by clearance mechanisms. Experiments are now in progress to determine whether the in vitro effects are dependent on the fiber parameters suggested as playing a role in the carcinogenic potency.}, } @article {pmid1606035, year = {1992}, author = {Rogers, A}, title = {Prediction of mesothelioma, lung cancer, and asbestosis in former Wittenoom asbestos workers.}, journal = {British journal of industrial medicine}, volume = {49}, number = {6}, pages = {451-452}, pmid = {1606035}, issn = {0007-1072}, mesh = {Asbestosis/*epidemiology ; Australia/epidemiology ; Forecasting/methods ; Humans ; Lung Neoplasms/*epidemiology ; Mesothelioma/*epidemiology ; }, } @article {pmid1604390, year = {1992}, author = {Westerfield, BT}, title = {Asbestos-related lung disease.}, journal = {Southern medical journal}, volume = {85}, number = {6}, pages = {616-620}, doi = {10.1097/00007611-199206000-00009}, pmid = {1604390}, issn = {0038-4348}, mesh = {Asbestos/*adverse effects ; Environmental Exposure ; Humans ; Lung Diseases/*etiology ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Pleural Diseases/*etiology ; Risk Factors ; }, abstract = {Asbestos is a versatile fibrous mineral that can cause lung disease and death. Asbestosis, benign pleural disease, lung cancer, and mesothelioma can all result from inhaling asbestos. The history of disease and exposure risks are discussed. The difficult assessment of risk and the long latency period for development of disease demand evaluation and regular surveillance of asbestos-exposed workers.}, } @article {pmid1571901, year = {1992}, author = {Huncharek, M}, title = {Changing risk groups for malignant mesothelioma.}, journal = {Cancer}, volume = {69}, number = {11}, pages = {2704-2711}, doi = {10.1002/1097-0142(19920601)69:11<2704::aid-cncr2820691113>3.0.co;2-f}, pmid = {1571901}, issn = {0008-543X}, mesh = {Asbestos/*adverse effects ; Humans ; Mesothelioma/*epidemiology/etiology ; *Occupational Exposure ; *Occupations ; }, abstract = {Although malignant mesothelioma is a relatively rare tumor, its incidence is rising. Much of the increase is attributable to widespread exposure to asbestos in past decades in asbestos-related industries. In recent years, it has become increasingly clear that mesothelioma risk is no longer confined to workers in the asbestos industry. This article reports a variety of recently identified "risk groups" and highlights the need for increased surveillance of these groups to document the occurrence of asbestos-related malignancy and the institution of measures for disease prevention.}, } @article {pmid1519873, year = {1992}, author = {McDonald, JC and Sébastien, P and Case, B and McDonald, AD and Dufresne, A}, title = {Ferruginous body counts in sputum as an index of past exposure to mineral fibres.}, journal = {The Annals of occupational hygiene}, volume = {36}, number = {3}, pages = {271-282}, doi = {10.1093/annhyg/36.3.271}, pmid = {1519873}, issn = {0003-4878}, mesh = {Adult ; Analysis of Variance ; Asbestos/*analysis ; Asbestosis/*diagnosis ; Case-Control Studies ; Cell Count ; Cohort Studies ; Cross-Sectional Studies ; Humans ; Lung Neoplasms/*diagnosis ; Macrophages ; Mesothelioma/*diagnosis ; Metalloproteins/*analysis ; Middle Aged ; Minerals/analysis ; Occupational Diseases/*diagnosis ; Occupational Exposure/*analysis ; Sputum/*chemistry ; }, abstract = {Previous work by our group among vermiculite miners exposed to fibrous tremolite demonstrated that asbestos body counts in sputum closely reflected intensity and duration of past exposure. In the present project sputum samples from nearly 600 volunteers from 11 cohorts of workers exposed to asbestos and other mineral fibres were found to contain much lower numbers of asbestos bodies than had been observed in vermiculite workers and these counts did not reliably reflect past levels of exposure. No evidence was found that occupational exposure to man-made mineral fibres led to any ferruginous body formation. Asbestos body counts appeared to differentiate between mesothelioma cases and controls and between levels of radiological asbestosis, but in both comparisons, based on small numbers, the power of discrimination was low. Substantial variation was found both in asbestos body and in macrophage counts in daily sampling of vermiculite workers but it was not sufficient to invalidate comparison between groups for epidemiological study. In individual subjects, however, little reliance can be put on results from a single sputum sample, particularly if negative.}, } @article {pmid1511551, year = {1992}, author = {Gaensler, EA}, title = {Asbestos exposure in buildings.}, journal = {Clinics in chest medicine}, volume = {13}, number = {2}, pages = {231-242}, pmid = {1511551}, issn = {0272-5231}, support = {HL 1173/HL/NHLBI NIH HHS/United States ; }, mesh = {Air Pollution, Indoor/*adverse effects/analysis ; Asbestos/*adverse effects ; Asbestosis/*etiology ; Construction Materials/*adverse effects/analysis/economics/standards ; Cost-Benefit Analysis ; *Environmental Exposure ; Humans ; Lung Neoplasms/*etiology ; Risk Factors ; }, abstract = {Asbestos-related diseases are dose-related. Among these, asbestosis has occurred only with the heavy exposures of the past, is a disappearing disease, and is of no concern with the very small exposures from building occupancy. A possibly increased incidence of lung cancer has been included in risk analysis, but probably is also related to high exposure in that both epidemiologic and experimental data suggest a link between the process of alveolar inflammation and fibrogenesis and carcinogenesis. The major concern has been mesothelioma in that it has occurred with much lower household and neighborhood exposure. Additionally, anxiety concerning buildings with ACM has been heightened by finding of friable asbestos in about 20% of public buildings, discovery of environmental asbestos fibers and asbestos bodies in autopsies, and demonstration of a linear relationship between exposure and lung cancer risk in occupational groups, inviting extrapolation to a much lower dose. Legislative and regulatory mandates, promotional activities of abatement companies, adverse court decisions placing the onus of repairs on asbestos manufacturers, and a "pandemic of mediagenic disease" all have contributed to panic among building owners, school boards, insurers, and others. In that there is neither clinical nor epidemiologic support for asbestos-related disease from building occupancy, risk estimates have been based on extrapolation from past experience with generally high-dose occupational exposure. However, only a few epidemiologic studies have contained quantitative estimates of exposure, and these have been measured in terms of all particles, with conversion to asbestos fibers uncertain and the fiber type and dimension largely unknown. To these uncertainties must be added the unproved assumption of a linear dose-response down to very low levels of exposure with no threshold. At the other end of the scale extrapolation has required measurements of present building exposure, and these have been revised downward as methods for collection and analysis have improved. Risk estimates in this country and abroad have assumed exposure to 0.001 f/mL, with indicated lifetime risks for cancer ranging from about 2 to 20 per 1 million students. However, these estimates have assumed mixed fiber exposure whereas most building exposure comes from chrysotile, which is much less toxic than the amphiboles.(ABSTRACT TRUNCATED AT 400 WORDS)}, } @article {pmid1452154, year = {1992}, author = {Wang, C and Luo, S and Liu, X}, title = {[Observation of the morphological genesis of pleural mesothelioma induced by asbestos in rats].}, journal = {Hua xi yi ke da xue xue bao = Journal of West China University of Medical Sciences = Huaxi yike daxue xuebao}, volume = {23}, number = {2}, pages = {181-184}, pmid = {1452154}, issn = {0257-7712}, mesh = {Animals ; Asbestos/*adverse effects ; Epithelium/pathology ; Hyperplasia/pathology ; Mesothelioma/*pathology ; Pleura/pathology ; Pleural Neoplasms/*pathology ; Rats ; Rats, Wistar ; }, abstract = {In order to observe the lesions of pleural mesothelia caused by asbestos, we injected asbestos fiber into the pleural cavity of Wistar rats. The result showed that there Was an obvious process for the morphological genesis of mesothelioma. Simple hyperplasia and stratified pleomorphic hyperplasia of mesothelial cells were found on the 30th and 106th day after the injection of asbestos fiber, respectively. The benign and malignant mesotheliomas were noted on the 300th day. Meanwhile, a two-way differentiation may be observed in the process of mesothelial hyperplasia.}, } @article {pmid1317792, year = {1992}, author = {Adachi, S and Kawamura, K and Kimura, K and Takemoto, K}, title = {Tumor incidence was not related to the thickness of visceral pleural in female Syrian hamsters intratracheally administered amphibole asbestos or manmade fibers.}, journal = {Environmental research}, volume = {58}, number = {1}, pages = {55-65}, doi = {10.1016/s0013-9351(05)80204-x}, pmid = {1317792}, issn = {0013-9351}, mesh = {Adenoma/chemically induced ; Animals ; Asbestos/*toxicity ; Asbestos, Amosite ; Asbestos, Amphibole ; Asbestos, Crocidolite ; Calcium Sulfate/toxicity ; Carbon/toxicity ; Cricetinae ; Female ; Glass ; Lung Neoplasms/*chemically induced ; Magnesium Sulfate/toxicity ; Mesocricetus ; Mesothelioma/chemically induced ; Pleura/*pathology ; Pleural Neoplasms/*chemically induced ; Silicon Dioxide/*toxicity ; Titanium/toxicity ; }, abstract = {Histological observations were performed on female Syrian hamsters 2 years after the intratracheal administration of amphibole asbestos, amosite, and crocidolite to evaluate the tumorigenicity of six types of fine manmade fibers (reported previously). A mesothelioma and a lung tumor were induced in 20 animals administered amosite, but no tumors were found in the crocidolite group. Because this incidence is not higher than that of manmade fibers, such as basic magnesium sulfate fiber [9 tumor-bearing hamsters in 20 hamsters (9/20)], metaphosphate fiber (5/20), calcium sulfate fiber (3/20), and fiberglass (2/20), it is suggested that some types of manmade fibers have a greater ability than asbestos to induce tumors. Moreover, as a specific observation in manmade fiber groups, tumors were induced at intracelial organs rather than at the pleural cavity. On the other hand, the average thickness of visceral pleura was higher in all asbestos and manmade fiber groups than in the control (2.9 microns), for instance, 36.95 microns in potassium titanate fiber group, 15.90 microns crocidolite group, 13.00 microns basic magnesium sulfate fiber group, and 10.45 microns in the rockwool group. Although both pleural thickening and mesothelioma are known as peculiar lesions in asbestos-exposed people, it might also be suggested that these lesions could be induced by different mechanisms from the result that there was no relation between the pleural thickening and mesothelioma incidence in hamsters.}, } @article {pmid1568184, year = {1992}, author = {Kishimoto, T}, title = {Intensity of exposure to asbestos in metropolitan Kure City as estimated by autopsied cases.}, journal = {Cancer}, volume = {69}, number = {10}, pages = {2598-2602}, doi = {10.1002/1097-0142(19920515)69:10<2598::aid-cncr2820691033>3.0.co;2-x}, pmid = {1568184}, issn = {0008-543X}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Asbestos/analysis ; Autopsy ; Environmental Monitoring/*methods ; Female ; Humans ; Japan ; Lung/*chemistry ; Lung Neoplasms/chemistry ; Male ; Mesothelioma/chemistry ; Middle Aged ; }, abstract = {In this study, the intensity of exposure to asbestos was evaluated in the residents of Kure City, the site of the Japanese naval shipyard, Kure. The number of asbestos bodies was counted in 728 autopsied cases from those treated surgically in Kure Kyosai Hospital. Five grams of lung tissue was lysed, and the number of asbestos bodies was counted with the use of light microscopic examination. By this method, the number of asbestos bodies detected in men was significantly higher than that in women. There was a peak between 60 and 70 years of age. The number of asbestos bodies in exposed cadavers in Kure City exceeded greatly that found in other districts of Japan. By this criterion, 58 of 109 patients with lung cancer had asbestos exposure, and 39 had a high exposure to asbestos. All 13 patients with malignant mesothelioma had a high exposure to asbestos. Excess asbestos exposure also was found in a large proportion of patients with gastric cancer, colon cancer, and acute leukemia. The crocidolite type of asbestos was detected frequently in patients of malignant mesothelioma or leukemia, and the chrysotile form was found in those with lung cancer.}, } @article {pmid1630045, year = {1992}, author = {Kishimoto, T}, title = {[Distribution of ferruginous bodies in the lung in cases of malignant pleural mesothelioma with definite occupational history of asbestos exposure].}, journal = {Nihon Kyobu Shikkan Gakkai zasshi}, volume = {30}, number = {5}, pages = {821-826}, pmid = {1630045}, issn = {0301-1542}, mesh = {Aged ; Asbestos/*adverse effects ; Female ; Humans ; Male ; Mesothelioma/*chemistry/etiology ; Metalloproteins/*metabolism ; Middle Aged ; *Occupational Exposure ; Pleural Neoplasms/*chemistry/etiology ; }, abstract = {The distribution of ferruginous bodies in the lung in cases of malignant pleural mesothelioma with definite occupational history of asbestos exposure was examined, and the length of ferruginous bodies and the kinds of asbestos fibers were also evaluated. Ferruginous bodies were most numerous in the upper lobes, especially in S1, and were least numerous in the lower lobes. On the other hand, the longest ferruginous bodies were detected in the lower lobes. Amosite and crocidolite (amphibole groups) were found in almost all cases of malignant pleural mesothelioma, but chrysotile was found in only one case. The longer fiber length of asbestos in the amphibole group was considered to be important in the carcinogenicity of malignant mesothelioma, since almost all cases of malignant mesothelioma originated from the lower pleura.}, } @article {pmid1619796, year = {1992}, author = {Koike, S}, title = {[Health effects of non-occupational exposure to asbestos].}, journal = {Sangyo igaku. Japanese journal of industrial health}, volume = {34}, number = {3}, pages = {205-215}, doi = {10.1539/joh1959.34.205}, pmid = {1619796}, issn = {0047-1879}, mesh = {Air Pollution, Indoor ; Asbestos/*adverse effects ; Automobiles ; *Environmental Exposure ; *Environmental Health ; Environmental Pollutants/adverse effects ; Housing ; Humans ; Lung Diseases/*etiology ; Mesothelioma/*etiology ; }, abstract = {Mesothelioma has occurred in a relative large number not only among miners but also among non-occupationally exposed persons living in the northwestern region of Cape State of South Africa, where crocidolite is mined and transported. The long-term residents of Thetford Mines in Quebec Province, Canada, who have never engaged in mining and milling of chrysolite have not shown an excess mortality of respiratory diseases. Tremolite in soil is responsible for mesothelioma among residents of certain geologic regions such as Cyprus, Corcica, northwestern Greece and Turkey. An increased prevalence of malignant mesothelioma has been reported among residents of three Turkish villages due to exposure to erionite fibers having a high carcinogenic potency. Mesothelioma has infrequently developed in wives who were exposed while washing the work clothes of their husbands contaminated with asbestos, especially amphiboles. The levels of airborne asbestos in public buildings and schools in the U.S.A. and England having walls and ceilings constructed with asbestos containing materials are approximately 1/100 of the permissible concentration of 0.2 f/cm3. The estimated risk from asbestos exposure in schools and buildings is lower than the level of other risks in other society. During the work of removing asbestos from buildings the asbestos concentration is remarkably increased and this persists for many weeks thereafter. The level of asbestos fibers released from brake linings of motor vehicles is higher along roads with heavy traffic, at intersections, and near toll booths than elsewhere. The concentration of asbestos fibers released from motor vehicles is generally low and not of the level to induce mesothelioma.}, } @article {pmid1609162, year = {1992}, author = {Hyers, TM and Ohar, JM and Crim, C}, title = {Clinical controversies in asbestos-induced lung diseases.}, journal = {Seminars in diagnostic pathology}, volume = {9}, number = {2}, pages = {97-101}, pmid = {1609162}, issn = {0740-2570}, mesh = {Airway Obstruction/etiology ; Asbestos/*adverse effects ; Asbestosis/*diagnosis ; Carcinoma, Bronchogenic/*etiology ; Humans ; Lung Diseases/*etiology ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Pleural Diseases/complications ; }, abstract = {Asbestos is a heterogeneous mineral fiber with considerable heat resistance and sound-abatement properties. It is relatively easily mined and processed and has been applied in a number of forms to ships and buildings. Unfortunately, respirable asbestos fibers have significant pathologic effects on the human lung and other organs. These effects can result in characteristic pleuropulmonary diseases, which become manifest after a latency period of 10 to 40 years from first exposure. This brief review will outline some major current controversies in the clinical approach to evaluation of asbestos-induced lung diseases.}, } @article {pmid1609161, year = {1992}, author = {Bedrossian, CW}, title = {Asbestos-related diseases: a historical and mineralogic perspective.}, journal = {Seminars in diagnostic pathology}, volume = {9}, number = {2}, pages = {91-96}, pmid = {1609161}, issn = {0740-2570}, mesh = {Asbestos/adverse effects/chemistry/*history ; Asbestosis/etiology ; Environmental Exposure/adverse effects/*history ; History, 16th Century ; History, 19th Century ; History, 20th Century ; History, Ancient ; History, Medieval ; Humans ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Mining ; }, } @article {pmid1609158, year = {1992}, author = {Roggli, VL}, title = {Quantitative and analytical studies in the diagnosis of mesothelioma.}, journal = {Seminars in diagnostic pathology}, volume = {9}, number = {2}, pages = {162-168}, pmid = {1609158}, issn = {0740-2570}, mesh = {Asbestos/adverse effects/*analysis ; Environmental Exposure/adverse effects ; Humans ; Mesothelioma/*diagnosis/etiology ; Microscopy, Electron ; Occupational Exposure/adverse effects ; Pleural Neoplasms/*diagnosis/etiology ; }, abstract = {The vast majority of patients with malignant mesothelioma of the pleura or peritoneum have an abnormal tissue asbestos content as assessed by digestion techniques. These procedures allow for the quantification of asbestos bodies, as well as numbers and types of mineral fibers. In general, analyses of mineral fiber content correlate well with occupational exposure history. Such analyses are useful for the identification of asbestos-related mesotheliomas and separation from those due to other causes.}, } @article {pmid1609155, year = {1992}, author = {Bedrossian, CW and Bonsib, S and Moran, C}, title = {Differential diagnosis between mesothelioma and adenocarcinoma: a multimodal approach based on ultrastructure and immunocytochemistry.}, journal = {Seminars in diagnostic pathology}, volume = {9}, number = {2}, pages = {124-140}, pmid = {1609155}, issn = {0740-2570}, mesh = {Adenocarcinoma/*pathology/ultrastructure ; Asbestos/adverse effects ; Diagnosis, Differential ; Environmental Exposure/adverse effects ; Epithelial Cells ; Epithelium/ultrastructure ; Humans ; Hyperplasia/diagnosis ; Immunohistochemistry ; Lung Neoplasms/immunology/*pathology/ultrastructure ; Mesothelioma/immunology/*pathology/ultrastructure ; Microscopy, Electron ; }, abstract = {Most compensations for asbestos-related deaths secondary to cancer center around mesothelioma and bronchogenic carcinoma. The differential diagnosis between mesothelioma and adenocarcinoma is a common and troublesome one, necessitating the correlation between clinical history, radiographic findings, and pathologic examination of tissues and cells. We describe a multimodal approach based on the use of routine and special stains, immunocytochemistry, and electron microscopy for distinguishing between mesothelioma and adenocarcinoma. Once a malignant diagnosis is arrived at by careful pathological examination, the tumor is classified as mesothelioma if mesothelial cells are identified as the constituent cells of the neoplasm. Mesothelial cells are recognized by (1) their main ultrastructural features: slender and elongated microvilli, abundant intermediate filaments, and lacking secretory granules; and (2) their characteristic immunocytochemical reactivity: positivity for cytokeratin, EMA, and vimentin, and negativity for carcinoembryonic antigen (CEA), B72-3, Leu-M1, and other gland-cell markers. A variety of methods have been attempted in an effort to distinguish between reactive and malignant mesothelial cells. In practice, however, such distinction depends more on experience and expertise than in any fool-proof ancillary tests. A number of these tests are discussed along with the illustration of classical and unusual examples of mesothelioma and other pleural tumors.}, } @article {pmid1609154, year = {1992}, author = {Koss, M and Travis, W and Moran, C and Hochholzer, L}, title = {Pseudomesotheliomatous adenocarcinoma: a reappraisal.}, journal = {Seminars in diagnostic pathology}, volume = {9}, number = {2}, pages = {117-123}, pmid = {1609154}, issn = {0740-2570}, mesh = {Adenocarcinoma/mortality/*pathology/therapy ; Aged ; Diagnosis, Differential ; Female ; Humans ; Male ; Mesothelioma/*pathology ; Middle Aged ; Neoplasm Metastasis ; Pleural Neoplasms/mortality/*pathology/therapy ; Sex Factors ; Smoking ; }, abstract = {Adenocarcinomas of or in lung that clinically and pathologically mimic diffuse pleural mesotheliomas are rare. We reviewed selected clinical and pathologic features of 15 autopsy/surgical cases previously reported in the medical literature and of 15 additional cases from the files of the Armed Forces Institute of Pathology (AFIP). Ninety percent of the patients were men. The median age was 61 years. Sixty-three percent of the patients smoked, 17% of them had possible or definite occupational exposure to asbestos, and one patient had microscopically proven asbestosis. Most patients had chest pain, shortness of breath, or cough, and had unilateral pleural effusion in the chest x-ray. At thoracotomy or at autopsy, numerous nodules, plaques, or a continuous rind of tumor was present over the pleural surface. Microscopically, the tumors showed simplified glands, nests, cords, papillary, tubulopapillary or biphasic patterns of growth. The neoplasms contained mucin that stained with diastase-predigested periodic acid-Schiff (PAS), mucicarmine, and alcian blue (with or without hyaluronidase predigestion). All patients died with/of tumor, with a mean survival of 4.7 months for those reported in the medical literature and of 7 months for those in the AFIP files. These adenocarcinomas therefore mimic pleural mesothelioma not only in their clinical and gross and microscopic appearance, but also in their prognosis.}, } @article {pmid1556763, year = {1992}, author = {Reynolds, T}, title = {Asbestos-linked cancer rates up less than predicted.}, journal = {Journal of the National Cancer Institute}, volume = {84}, number = {8}, pages = {560-562}, pmid = {1556763}, issn = {0027-8874}, mesh = {Asbestos/*adverse effects ; Humans ; Mesothelioma/*epidemiology/etiology ; Occupational Diseases/*epidemiology/etiology ; Ships ; United States/epidemiology ; }, } @article {pmid1609299, year = {1992}, author = {Miller, WT and Gefter, WB and Miller, WT}, title = {Asbestos-related chest diseases: plain radiographic findings.}, journal = {Seminars in roentgenology}, volume = {27}, number = {2}, pages = {102-120}, doi = {10.1016/0037-198x(92)90053-5}, pmid = {1609299}, issn = {0037-198X}, mesh = {Asbestos/*adverse effects ; Asbestosis/etiology ; Humans ; Lung Diseases/diagnostic imaging/*etiology ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Pleural Diseases/diagnostic imaging/*etiology ; Pleural Neoplasms/etiology ; Pulmonary Atelectasis/etiology ; Radiography ; }, abstract = {In summary, there are a wide range of pulmonary manifestations seen in asbestos-exposed individuals from pleural and parenchymal fibrosis to pleural and parenchymal malignancy. The chest roentgenogram has assumed an important role in the detection and surveillance of asbestos-related pleural and parenchymal changes.}, } @article {pmid1610769, year = {1992}, author = {Schultz, M and Kühne, W}, title = {[The problems of early diagnosis of diffuse malignant mesothelioma from the pathologo-anatomic view].}, journal = {Zentralblatt fur Pathologie}, volume = {138}, number = {2}, pages = {85-90}, pmid = {1610769}, issn = {0863-4106}, mesh = {Animals ; Diagnosis, Differential ; Humans ; Mesothelioma/diagnosis/*pathology ; Pleural Neoplasms/*diagnosis/pathology ; }, abstract = {An account is given in this paper of particular problems associated with early detection of mesotheliomatous alterations and differential diagnosis for their distinction from reactive mesothelial cell proliferations. Reference is made, in that context, to pathologico-anatomic experience obtained from postmortem and biopsy samples of human malignant mesotheliomas and animal experiments, following exposure to various asbestos-containing dusts. Diagnoses, such as "premesotheliomatous alteration" or "early mesothelioma", in other words, differentiation between benign and malignant, consequently, appear to be unjustified.}, } @article {pmid1609305, year = {1992}, author = {Jones, RN}, title = {Asbestos exposures and thoracic neoplasms.}, journal = {Seminars in roentgenology}, volume = {27}, number = {2}, pages = {94-101}, doi = {10.1016/0037-198x(92)90052-4}, pmid = {1609305}, issn = {0037-198X}, mesh = {Asbestos/*adverse effects ; Asbestosis/etiology ; Humans ; Lung Neoplasms/diagnostic imaging/*etiology ; Mesothelioma/etiology ; Pleural Neoplasms/etiology ; Radiography ; Risk Factors ; Thoracic Neoplasms/*etiology ; Time Factors ; }, } @article {pmid1591306, year = {1992}, author = {Ruffie, P}, title = {Pleural mesothelioma.}, journal = {Current opinion in oncology}, volume = {4}, number = {2}, pages = {334-341}, doi = {10.1097/00001622-199204000-00015}, pmid = {1591306}, issn = {1040-8746}, mesh = {Animals ; Flow Cytometry ; Humans ; *Mesothelioma/etiology/pathology/therapy ; *Pleural Neoplasms/etiology/pathology/therapy ; Tomography, X-Ray Computed ; }, abstract = {Diffuse pleural malignant mesothelioma (DMM) is an uncommon tumor in the general population, but its incidence can be very high in persons exposed to asbestos. There has been controversy about the role of the different fiber types and their responsibility for causing DMM, particularly with chrysotile. Distinguishing between DMM and peripheral adenocarcinoma with pleural involvement is a frequent diagnostic problem. Immunohistochemical markers (positive for vimentin and negative for carcinoembryonic antigen and Leu M1) and electronmicroscopy aid in the diagnosis. Therapeutic results remain poor, and cure of DMM is rare. Local treatments such as surgery or radiation therapy are technically difficult because of the extent of disease. DMM continues to be a chemoresistant tumor. Because DMM is rare, study of this tumor has been hampered by the limited number of available patients in any given institution. Therefore, animal models or representative human malignant mesothelioma cell lines are needed for a dual investigation: first of the basic biology of this disease and second for a preclinical evaluation of chemotherapeutic agents and recombinant anticancer cytokines alone or in combination. Ongoing trials confirm that DMM is resistant to standard forms of therapy, but mesothelial cells are susceptible to immune effector cells and cytokines in in vitro and in vivo models. Thus, recombinant interferon-alpha, -beta, and -gamma have been used for both local and systemic treatment, as has interleukin-2 with and without autologous lymphokine-activated killer cells. In addition, substantial experimental evidence suggests synergy between cytotoxic drugs and cytokines.}, } @article {pmid1577967, year = {1992}, author = {Wilson, GE and Hasleton, PS and Chatterjee, AK}, title = {Desmoplastic malignant mesothelioma: a review of 17 cases.}, journal = {Journal of clinical pathology}, volume = {45}, number = {4}, pages = {295-298}, pmid = {1577967}, issn = {0021-9746}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Collagen/analysis ; Female ; Humans ; Male ; Mesothelioma/chemistry/etiology/*pathology ; Middle Aged ; Neoplasm Invasiveness ; Pleural Neoplasms/chemistry/etiology/*pathology ; }, abstract = {AIMS: To identify the histological features of desmoplastic mesothelioma, and to determine its incidence and prognosis.

METHODS: Two hundred and fifty five cases of malignant mesothelioma were examined over seven years (1982-9) to identify the desmoplastic variant. Sections were cut at 5 microns and stained with haemotoxylin and eosin and with CAM 5.2 (Dakopatts). Asbestos fibre counts were carried out by light microscopy in 14 cases using the potash digestion method.

RESULTS: Seventeen cases were identified as desmoplastic mesothelioma giving an incidence of 6.6%. In 11 cases the cell type in more cellular areas was sarcomatous and in six others it was biphasic. The mean survival time from onset of symptoms to death was 5.8 months for the sarcomatous variant and 6.8 months for the biphasic variant. Twelve of 16 patients had had previous occupational exposure to asbestos, ranging from five months to 43 years. The diagnosis of desmoplastic mesothelioma was only accepted if acellular connective tissue comprised 50% or more of the tumour bulk. Also seen was collagen necrosis, anastomosing bands of often hyalinised collagen with a prominent storiform pattern, and where cellular detail was present there were hyperchromatic nuclei.

CONCLUSIONS: Desmoplastic mesothelioma is a rare variant of malignant mesothelioma with a storiform collagen pattern, collagen necrosis, bland acellular collagen and focal cytological features of malignancy. Though rare, it is important to recognise this variant and distinguish it from a pleural plaque, nonspecific reactive pleural fibrosis, pleurisy, rheumatoid disease, or, rarely, spindle cell sarcomas.}, } @article {pmid1571274, year = {1992}, author = {Pigott, GH and Ishmael, J}, title = {The effects of intrapleural injections of alumina and aluminosilicate (ceramic) fibres.}, journal = {International journal of experimental pathology}, volume = {73}, number = {2}, pages = {137-146}, pmid = {1571274}, issn = {0959-9673}, mesh = {Aluminum Oxide/*toxicity ; Aluminum Silicates/*toxicity ; Animals ; Asbestos/toxicity ; Female ; Hot Temperature ; Male ; Mesothelioma/chemically induced ; Peritoneal Neoplasms/chemically induced ; Pleural Neoplasms/*chemically induced/etiology ; Rats ; Rats, Inbred Strains ; }, abstract = {Groups of rats, 24 male and 24 female, approximately 8 weeks old, were dosed by a single intrapleural injection with a saline suspension of refractory alumina fibres (Saffil fibres ICI plc) either as manufactured or after extensive thermal ageing; or one of two aluminosilicate ('ceramic') fibres with different diameter distributions. Similar groups were dosed with a suspension of UICC chrysotile A asbestos or saline solution to serve as positive and negative controls respectively. Rats were maintained to 85% mortality and all decedents and terminal sacrifices were closely examined for the presence of mesothelioma. Malignant mesothelioma was diagnosed in ten rats, seven dosed with asbestos and three dosed with aluminosilicate fibre B. No mesothelioma was detected in any rat dosed with Saffil fibres or aluminosilicate fibre A or in negative controls. The results support the predicted inert nature of Saffil alumina fibres and provide further evidence for the importance of fibre dimension in the induction of mesothelioma. The implication of the results for inhalation exposures is discussed.}, } @article {pmid1553915, year = {1992}, author = {Goetz, SP and Robinson, RA and Landas, SK}, title = {Extraskeletal myxoid chondrosarcoma of the pleura. Report of a case clinically simulating mesothelioma.}, journal = {American journal of clinical pathology}, volume = {97}, number = {4}, pages = {498-502}, doi = {10.1093/ajcp/97.4.498}, pmid = {1553915}, issn = {0002-9173}, mesh = {Aged ; Chondrosarcoma/*diagnosis/pathology ; Diagnosis, Differential ; Humans ; Immunoenzyme Techniques ; Male ; Mesothelioma/*diagnosis ; Microscopy, Electron ; Pleural Neoplasms/*diagnosis/pathology ; }, abstract = {A primary extraskeletal myxoid chondrosarcoma of the pleura that clinically mimicked a malignant mesothelioma in a 66-year-old man with a history of asbestos exposure is described. Although exceedingly rare in this location, the characteristic histologic features, immunohistochemical reactivities, and ultrastructural features support the diagnosis of extraskeletal myxoid chondrosarcoma. Many ferruginous (asbestos) bodies consistent with the exposure history were found in the lung tissue sections and confirmed by energy-dispersive spectrometry. This case demonstrates an unusual pleural primary neoplasm associated with asbestos.}, } @article {pmid1313399, year = {1992}, author = {Van der Meeren, A and Fleury, J and Nebut, M and Monchaux, G and Janson, X and Jaurand, MC}, title = {Mesothelioma in rats following intrapleural injection of chrysotile and phosphorylated chrysotile (chrysophosphate).}, journal = {International journal of cancer}, volume = {50}, number = {6}, pages = {937-942}, doi = {10.1002/ijc.2910500620}, pmid = {1313399}, issn = {0020-7136}, mesh = {Animals ; Asbestos/*toxicity ; Asbestos, Serpentine ; Carcinogens/*toxicity ; Male ; Mesothelioma/*chemically induced/pathology ; Phosphorus/*toxicity ; Phosphorylation ; Pleural Neoplasms/*chemically induced/pathology ; Rats ; Rats, Inbred Strains ; }, abstract = {Pathological effects of asbestos are probably dependent on the size and surface properties of the fibers. Surface-modified chrysotile fibers were injected into the pleural cavity of rats to investigate the potency of the fiber to induce mesothelioma. Chrysotile fibers were modified by a phosphorylation process, resulting in the presence of phosphorus at the fiber surface. Phosphorylated samples were characterized by enhanced durability and reduced affinity for biological macromolecules. Five samples were tested: 1 untreated and 4 phosphorylated. ChrP1, ChrP2 and ChrP3 corresponded to phosphorylated samples obtained by first, second and third passages through an Alpine classifier; Pm was defibrillated ChrP1. The number of fibers per microgram and the size distribution were determined by transmission electron microscopy and classified in 4 size groups. Groups of 35 rats were inoculated with 20 mg of fibers suspended in 0.9% NaCl solution. No mesothelioma was found in the saline controls. All fiber samples were proficient in producing mesothelioma; the percentages were different between groups and untreated chrysotile but not significantly so. The differences may be explained on the basis of the number of fibers injected which were greater than 8 microns in length and less than 0.25 microns in diameter. The findings of a proficiency of long fibers to produce mesothelioma, previously reported by others for glass fibers, could be applied to chrysotile.}, } @article {pmid1313398, year = {1992}, author = {Brandt-Rauf, PW and Smith, S and Hemminki, K and Koskinen, H and Vainio, H and Niman, H and Ford, J}, title = {Serum oncoproteins and growth factors in asbestosis and silicosis patients.}, journal = {International journal of cancer}, volume = {50}, number = {6}, pages = {881-885}, doi = {10.1002/ijc.2910500610}, pmid = {1313398}, issn = {0020-7136}, support = {OH00076/OH/NIOSH CDC HHS/United States ; }, mesh = {Aged ; Amino Acid Sequence ; Antibodies, Monoclonal ; Asbestos/adverse effects ; Asbestosis/*blood/complications ; Biomarkers, Tumor/*blood ; Cohort Studies ; Female ; Growth Substances/*blood ; Humans ; Male ; Molecular Sequence Data ; Neoplasms/etiology ; Occupational Exposure ; Oncogene Proteins/*blood ; Peptides/immunology ; Proto-Oncogene Proteins p21(ras)/analysis ; Risk Factors ; Silicon Dioxide/adverse effects ; Silicosis/*blood/complications ; }, abstract = {Levels of 9 different oncoproteins and growth factors were assayed by immunoblotting with monoclonal antibodies in 91 serum samples collected between March 1983 and August 1987 from 46 pneumoconiosis patients (36 asbestosis, 10 silicosis) at high risk for the development of cancer. Follow-up of these patients through June 1991 showed that 18 had developed cancer (11 lung, 2 pleural mesothelioma, 2 transitional-cell carcinomas of the urinary bladder, 1 osteosarcoma, 1 non-Hodgkin's lymphoma, 1 adenocarcinoma of the gallbladder). Increased serum levels of ras oncogene-related protein (p21) were found in 7 of the 18 patients who developed cancer (5 lung, 2 pleural mesothelioma) versus 2 of the 28 patients without cancer, a statistically significant difference (p = 0.012). In addition, 6 of the 7 p21-positive cancer cases had positive serum samples prior to clinical diagnosis of disease (average = 16.3 months, range = 3-26 months prior to diagnosis), suggesting that elevated serum p21 levels may be a useful marker for earlier detection in a significant percentage of respiratory malignancies. Finally, elevated serum levels of PDGF-related protein were detected significantly more frequently in advanced pneumoconiosis cases (ILO radiographic classification of 2/1 or greater) than in less advanced cases (80% vs. 41.9%; p = 0.016), and there was a tendency for these PDGF-positive patients to have progression of their disease (68.2% vs. 41.7%; p = 0.065), suggesting that elevated serum PDGF levels may be a marker for the development of severe and progressive pneumoconioses.}, } @article {pmid1572439, year = {1992}, author = {Sandén, A and Järvholm, B and Larsson, S and Thiringer, G}, title = {The risk of lung cancer and mesothelioma after cessation of asbestos exposure: a prospective cohort study of shipyard workers.}, journal = {The European respiratory journal}, volume = {5}, number = {3}, pages = {281-285}, pmid = {1572439}, issn = {0903-1936}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Asbestosis/epidemiology ; Humans ; Lung Neoplasms/epidemiology/*etiology ; Male ; Mesothelioma/epidemiology/*etiology ; Middle Aged ; Naval Medicine/*statistics & numerical data ; Occupational Diseases/epidemiology/*etiology ; Pleural Neoplasms/epidemiology/*etiology ; Prospective Studies ; Risk Factors ; *Ships ; Smoking/adverse effects/epidemiology ; Sweden/epidemiology ; Time Factors ; }, abstract = {A prospective cohort study of 3,893 shipyard workers, mainly exposed to chrysotile, indicated no increased risk of lung cancer 7-15 yrs after exposure to asbestos had ceased. The shipyard workers, however, had an increased risk of pleural mesotheliomas with 11 observed cases versus 1.5 expected. An explanation for these observations may be that asbestos may have different carcinogenic mechanisms in causing lung cancer and mesothelioma. A non-increased risk of lung cancer some years after exposure to asbestos has stopped is in accordance with asbestos acting as a promotor. The high risk of mesothelioma, on the other hand, may indicate that asbestos acts as a complete carcinogen in developing this disease.}, } @article {pmid1548893, year = {1992}, author = {Kini, U and Shariff, S and Thomas, JA}, title = {Primary pleural mesotheliomas in south India: a 25-year study.}, journal = {Journal of surgical oncology}, volume = {49}, number = {3}, pages = {196-201}, doi = {10.1002/jso.2930490313}, pmid = {1548893}, issn = {0022-4790}, mesh = {Adult ; Aged ; Biopsy ; Female ; Follow-Up Studies ; Humans ; India/epidemiology ; Male ; Mesothelioma/chemistry/*diagnosis/epidemiology/pathology ; Middle Aged ; Pleural Neoplasms/chemistry/*diagnosis/epidemiology/pathology ; Prevalence ; }, abstract = {In this report from South India, 15 patients with primary pleural mesothelioma have been diagnosed in the 25-year period 1, April 1966 through 31, March 1991, representing 0.02% of 76,239 biopsies received. The patients were mainly male with a mean age of 46.5 years. All except two had lived in urban Bangalore. None had been exposed to asbestos. The presentation clinically was peculiar, being continuous pricking pain, breathlessness, and cough with sputum. Physical and roentgenogram examination showed massive pleural effusion with irregular pleural thickening. Thoracotomy findings showed a distinct sessile nodularity with many slit-like spaces. Histologically, 14 were epithelial type mesotheliomas and 1 was a sarcomatous type. While the epithelial type neoplasms showed patchy squamoid differentiation, all showed mucin production. The CEA was always observed in areas of moderate differentiation. Spread occurred centrifugally to local structures on the same side as the lesion.}, } @article {pmid1397402, year = {1992}, author = {Himelstein, A}, title = {Malignant mesothelioma.}, journal = {Delaware medical journal}, volume = {64}, number = {3}, pages = {193-201}, pmid = {1397402}, issn = {0011-7781}, mesh = {Asbestos/*adverse effects ; Combined Modality Therapy ; Humans ; *Lung Neoplasms/chemically induced/diagnosis/therapy ; Male ; *Mesothelioma/chemically induced/diagnosis/therapy ; Middle Aged ; }, } @article {pmid1392518, year = {1992}, author = {Rittinghausen, S and Ernst, H and Muhle, H and Mohr, U}, title = {Atypical malignant mesotheliomas with osseous and cartilaginous differentiation after intraperitoneal injection of various types of mineral fibres in rats.}, journal = {Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie}, volume = {44}, number = {1}, pages = {55-58}, doi = {10.1016/S0940-2993(11)80138-7}, pmid = {1392518}, issn = {0940-2993}, mesh = {Abdominal Neoplasms/etiology/*pathology ; Animals ; Bone and Bones/drug effects/*pathology ; Cartilage/drug effects/*pathology ; Cell Differentiation/drug effects ; Female ; Injections, Intraperitoneal ; Mesothelioma/etiology/*pathology/secondary ; Minerals/*administration & dosage ; Rats ; Rats, Wistar ; }, abstract = {The histopathological appearance of malignant mesotheliomas with osseous and cartilaginous differentiation is described in detail. Bone and cartilage occurred in mixed and sarcomatoid mesotheliomas which were induced by intraperitoneal injection of various types of asbestos fibres (asbestos cement, crocidolite, UICC-amosite, UICC-chrysotile B, Calidria-chrysotile). Bone or cartilage were found in 32.7% of mixed mesothelioma and in 12.8% of sarcomatoid mesotheliomas.}, } @article {pmid1737433, year = {1992}, author = {Guest, PJ and Reznek, RH and Selleslag, D and Geraghty, R and Slevin, M}, title = {Peritoneal mesothelioma: the role of computed tomography in diagnosis and follow up.}, journal = {Clinical radiology}, volume = {45}, number = {2}, pages = {79-84}, doi = {10.1016/s0009-9260(05)80059-5}, pmid = {1737433}, issn = {0009-9260}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Ascites/diagnostic imaging ; Evaluation Studies as Topic ; Female ; Follow-Up Studies ; Humans ; Male ; Mesothelioma/*diagnostic imaging/etiology/pathology ; Middle Aged ; Occupational Diseases/etiology ; Omentum/diagnostic imaging ; Peritoneal Neoplasms/*diagnostic imaging/etiology/pathology ; *Tomography, X-Ray Computed ; }, abstract = {Computed tomography (CT) was performed on 15 patients with proven peritoneal mesothelioma. Eight of these patients underwent follow-up CT. It was found that a discrete and measurable mass is unusual in comparison with the common occurrence of ascites and that therefore CT has little role in quantifying the disease. Ascites is usually a prominent feature. Other features (e.g. omental infiltration) were evaluated and these could be used to assess disease progression.}, } @article {pmid1565787, year = {1992}, author = {Gartenschläger, M}, title = {[Asbestosis accompanied by primary peritoneal mesothelioma].}, journal = {Der Radiologe}, volume = {32}, number = {2}, pages = {83-86}, pmid = {1565787}, issn = {0033-832X}, mesh = {Asbestosis/*complications ; Female ; Humans ; Mesothelioma/diagnostic imaging/*etiology ; Middle Aged ; Peritoneal Neoplasms/diagnostic imaging/*etiology ; Tomography, X-Ray Computed ; }, abstract = {Diffuse, continuous abdominal pain and weight loss of 10 kg in 3 months were observed in a 57-year-old female patient. A CT examination of the abdomen was requested to rule out a malignant gynecological tumor. The CT study, however, showed a small amount of ascites and a thick sheet-like mass covering the internal anterior abdominal wall. On the basis of these CT findings, a peritoneal mesothelioma was suspected, which was confirmed by diagnostic laparotomy. The patient's history revealed exposure to asbestos at work from 21 to 24 years of age. The following signs of asbestosis and asbestos-related pleural disease were observed in the chest X-ray film: small opacities in the lower zones of both lungs, diffuse pleural thickening, a plaque on the right diaphragm, and small bilateral pleural effusions. In cases of suspected occupational illness such as that presented here, each physician concerned including the radiologist involved in the diagnosis, is required to advise the social insurance institution responsible.}, } @article {pmid1463974, year = {1992}, author = {Pluygers, E and Baldewyns, P and Minette, P and Beauduin, M and Gourdin, P and Robinet, P}, title = {Biomarker assessments in asbestos-exposed workers as indicators for selective prevention of mesothelioma or bronchogenic carcinoma: rationale and practical implementations.}, journal = {European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP)}, volume = {1}, number = {2}, pages = {129-138}, doi = {10.1097/00008469-199202000-00005}, pmid = {1463974}, issn = {0959-8278}, mesh = {Acetylcysteine/therapeutic use ; Antigens, Neoplasm/blood ; Asbestos/*adverse effects ; Ascorbic Acid/therapeutic use ; Biomarkers, Tumor/*blood ; Carcinoembryonic Antigen/blood ; Carcinoma, Bronchogenic/blood/*prevention & control ; Carotenoids/blood/therapeutic use ; Cohort Studies ; Ferritins/blood ; Humans ; Hyaluronic Acid/blood ; Longitudinal Studies ; Lung Neoplasms/blood/*prevention & control ; Male ; Mesothelioma/blood/*prevention & control ; Middle Aged ; Occupational Diseases/blood/*prevention & control ; *Occupational Exposure ; Peptides/blood ; Riboflavin/therapeutic use ; Selenium/blood/therapeutic use ; Tissue Polypeptide Antigen ; Vitamin A/blood ; Vitamin E/blood/therapeutic use ; beta Carotene ; }, abstract = {In the first part of this study we have shown how the serum levels of four selected tumour markers, namely tissue polypeptide antigen (TPA), carcino-embryonic antigen (CEA), hyaluronic acid (HA) and ferritin, display patterns characteristic of mesothelioma (M) or bronchogenic carcinoma (BC) in asbestos-exposed workers, and we hypothesize that the differences in marker patterns correspond to differences in carcinogenesis mechanisms. In a preliminary study, we found these specific marker patterns in 5/19 exposed workers of whom only one demonstrated any radiological signs of disease. Thus these specific marker patterns may be early events, occurring long (possibly years) before the classical radiological signs of exposure to asbestos. Accordingly they afford an optimal opportunity for prevention which should be adapted to the carcinogenesis mechanism as it is revealed by the marker pattern; it is aimed at antagonizing free radical carcinogenesis in all persons with TPA levels in excess of 100 U/l or Ferritin in excess of 400 ng/ml, and at inhibiting chemical carcinogenesis in those having elevated CEA levels (over 3 ng/ml). The mechanisms involved in these inhibitory processes are described and discussed, as well as the practical implementations that proceed from them. A prevention trial is now being started among 300 active and retired workers of an asbestos-cement works in northern France; the design of the study is presented. This prevention programme should be maintained over many years and holds a strong potential for reducing the untoward effects of exposure to asbestos.}, } @article {pmid1311197, year = {1992}, author = {Calisti, R and De Giuli, P and Ghione, GL}, title = {An update of cancer mortality among chrysotile asbestos miners in Balangero, northern Italy.}, journal = {British journal of industrial medicine}, volume = {49}, number = {2}, pages = {144}, pmid = {1311197}, issn = {0007-1072}, mesh = {Aged ; Asbestos/*adverse effects ; Asbestos, Serpentine ; Humans ; Italy ; Male ; Mesothelioma/*etiology ; *Mining ; Pleural Neoplasms/*etiology ; }, } @article {pmid1309438, year = {1992}, author = {Walker, C and Bermudez, E and Stewart, W and Bonner, J and Molloy, CJ and Everitt, J}, title = {Characterization of platelet-derived growth factor and platelet-derived growth factor receptor expression in asbestos-induced rat mesothelioma.}, journal = {Cancer research}, volume = {52}, number = {2}, pages = {301-306}, pmid = {1309438}, issn = {0008-5472}, mesh = {Animals ; Asbestos ; Blotting, Northern ; Blotting, Western ; Gene Expression ; Mesothelioma/genetics/*metabolism ; Platelet-Derived Growth Factor/*metabolism ; RNA, Messenger/genetics ; RNA, Neoplasm/genetics ; Rats ; Receptors, Cell Surface/*metabolism ; Receptors, Platelet-Derived Growth Factor ; Tumor Cells, Cultured ; }, abstract = {Although altered expression of platelet-derived growth factor (PDGF) is a hallmark of human mesothelioma, expression of PDGF receptors has not been characterized in this cell type. In addition, the expression of this growth factor and its cognate receptor in rodent mesothelioma has not been investigated. In this study, examination of transformed mesothelial cells derived from asbestos-induced rat mesotheliomas revealed that these cells expressed high affinity PDGF receptors (Kd = 0.5 nM) and receptor number was 1.6 x 10(5)/cell. Western analysis using antibodies specific for either the alpha-type or beta-type PDGF receptor and Northern analysis using probes specific for alpha- and beta-type receptor RNA transcripts indicated that these cells expressed beta-type PDGF receptors but that alpha-type receptors could not be detected. However, when the mesothelioma-derived cells were examined for the expression of PDGF, no expression of this growth factor could be detected. The transformed cells expressed no detectable A- or B-chain PDGF RNA transcripts; and using a competitive enzyme immunoassay specific for isoforms containing the B chain of PDGF and a sandwich enzyme-linked immunosorbent assay specific for A-chain-containing isoforms, neither AA, nor AB, nor BB isoforms of this growth factor could be detected in medium conditioned by these cells. The absence of alterations in PDGF expression in rat mesothelioma, in contrast to the data for the human disease, suggests that the production of this growth factor by transformed mesothelial cells may be species specific.}, } @article {pmid1729111, year = {1992}, author = {Kishimoto, T}, title = {Cancer due to asbestos exposure.}, journal = {Chest}, volume = {101}, number = {1}, pages = {58-63}, doi = {10.1378/chest.101.1.58}, pmid = {1729111}, issn = {0012-3692}, mesh = {Acute Disease ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Colonic Neoplasms/etiology/pathology ; Female ; Humans ; Leukemia/etiology/pathology ; Lung/pathology ; Lung Neoplasms/etiology/pathology ; Male ; Mesothelioma/etiology/pathology ; Middle Aged ; Neoplasms/*etiology/pathology ; Neoplasms, Multiple Primary/etiology/pathology ; Occupational Diseases/*etiology/pathology ; Occupational Exposure ; }, abstract = {To determine the relationship between malignancies and asbestos exposure, the number of asbestos bodies in wet lung tissue was counted by light microscopy according to the modified method of Smith and Naylor, and occupational histories were examined. The results revealed that 17 (89 percent) of 19 malignant mesotheliomas, 39 (38 percent) of 104 lung cancers, 23 (37 percent) of 62 gastric cancers, and 13 (28 percent) of 45 colon cancers were shown to be cases with asbestos exposure. These values were significantly higher than those of noncancerous cases (200 cases). It is of interest that five out of ten cases of leukemia were related to asbestos exposure. Nearly all multiple cancers including lung and gastric cancer in this study were also cases with asbestos exposure. Additional research should be conducted on the carcinogenicity of asbestos for multiple cancers.}, } @article {pmid1621694, year = {1992}, author = {Rapiti, E and Turi, E and Forastiere, F and Borgia, P and Comba, P and Perucci, CA and Axelson, O}, title = {A mortality cohort study of seamen in Italy.}, journal = {American journal of industrial medicine}, volume = {21}, number = {6}, pages = {863-872}, doi = {10.1002/ajim.4700210609}, pmid = {1621694}, issn = {0271-3586}, mesh = {Adolescent ; Adult ; Aged ; Cause of Death ; Cohort Studies ; Humans ; Italy/epidemiology ; Life Tables ; Lung Neoplasms/mortality ; Male ; Middle Aged ; *Naval Medicine ; Occupational Diseases/*mortality ; }, abstract = {A total of 2,208 male subjects, enrolled as merchant marine seamen at the Civitavecchia (Italy) harbor from 1936 to 1975 were followed up through 1989 in order to evaluate their mortality experience. Available information about the number of sailings made it possible to divide subjects into two subgroups: 948 workers with at least one sailing (cohort A) and 1,260 with no reported sailing (cohort B). Fewer than expected overall deaths were observed in both cohorts (cohort A: SMR = 0.83; cohort B: SMR = 0.81), mainly due to a lower mortality from circulatory, respiratory, and digestive diseases. Lung cancer deaths were significantly increased in cohort A (O = 30, SMR = 1.71, 95% CI = 1.15-2.44), whereas no excess was observed in cohort B (O = 6, SMR = 0.57, 95% CI = 0.21-1.26). Among subjects employed aboard ship, a trend in SMRs for lung cancer increasing with duration of employment was observed. Furthermore, three neoplasms of other parts of the respiratory system (including one mesothelioma) were detected in cohort A (SMR = 5.87), and one in cohort B. The study substantiates an increased risk of respiratory cancer among subjects with an occupational history of sailing; past exposure to asbestos and to other environmental carcinogens aboard could be implicated.}, } @article {pmid1620713, year = {1992}, author = {Kane, AB}, title = {Animal models of mesothelioma induced by mineral fibers: implications for human risk assessment.}, journal = {Progress in clinical and biological research}, volume = {374}, number = {}, pages = {37-50}, pmid = {1620713}, issn = {0361-7742}, support = {R01 ES 03189/ES/NIEHS NIH HHS/United States ; R01 ES 03721/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Asbestos/*adverse effects ; Humans ; Lung Neoplasms/*etiology ; Mice ; Occupational Exposure ; Risk Factors ; }, } @article {pmid1609814, year = {1992}, author = {Dodoli, D and Del Nevo, M and Fiumalbi, C and Iaia, TE and Cristaudo, A and Comba, P and Viti, C and Battista, G}, title = {Environmental household exposures to asbestos and occurrence of pleural mesothelioma.}, journal = {American journal of industrial medicine}, volume = {21}, number = {5}, pages = {681-687}, doi = {10.1002/ajim.4700210508}, pmid = {1609814}, issn = {0271-3586}, mesh = {Asbestos/*adverse effects ; Environmental Exposure/*adverse effects ; Female ; Humans ; Incidence ; Italy/epidemiology ; Male ; Mesothelioma/epidemiology/*etiology ; Pleural Neoplasms/epidemiology/*etiology ; }, abstract = {We reviewed the certificates of 39,650 deaths which occurred in the period 1975-1988 in Leghorn and of 45,900 in La Spezia (Italy) in the period 1958-1988. In total 262 cases have been recorded as pleural mesothelioma. The main occupational exposures occurred in the shipbuilding industry. Regarding non-occupational exposures to asbestos, 13 cases of mesothelioma were found in women who had washed the work clothes of their relatives at home; we also found other domestic uses of asbestos which were rarely or never discussed previously in the literature: six cases might be explained by the installation of fireproof or non-conductive materials in the domestic environment. These exposures probably are more frequent than realized until now.}, } @article {pmid1606507, year = {1992}, author = {Boutin, C and Rey, F and Gouvernet, J}, title = {[Malignant mesothelioma: prognostic factors in a series of 125 patients studied from 1973 to 1987].}, journal = {Bulletin de l'Academie nationale de medecine}, volume = {176}, number = {1}, pages = {105-14; discussion 115-7}, pmid = {1606507}, issn = {0001-4079}, mesh = {Aged ; Female ; Humans ; Male ; Mesothelioma/*pathology ; Middle Aged ; Pleural Neoplasms/*pathology ; Prognosis ; Thoracoscopy ; }, abstract = {A continuous series of 125 patients hospitalized between 1973 and 1987 with pleural malignant mesothelioma were the subjects of this stepwise analysis. A diagnostic thoracoscopy was carried out in every patient and the histopathological diagnosis confirmed by the French Mesothelioma Panel of Pathologists. The main characteristics of the patients were: mean age 64 +/- 1 year, 104 male, 21 female; previous asbestos exposure was present in 98. The histopathological type was epithelial in 90, mixed in 22, fibrosarcomatous in 13. The endoscopic aspect was analysed in the same manner from the beginning as follows: involvement of the parietal, diaphragmatic or visceral pleura; extension of the tumor into the pleural cavity, macroscopic aspects of the lesions. According to the Butchart's classification 56 patients were at stage I, 61 at stage II, 3 at stage III, 5 at stage IV. A multivariate analysis (Cox model) showed that the best prognostic factor is the stage I which can be divided in 2 subtypes: exclusive involvement of the parietal and diaphragmatic pleura without invasion of the visceral pleura: stage IA (median survival 31.2 months). It is 6.75 months as soon as the visceral pleura is invaded (stade IB).}, } @article {pmid1585954, year = {1992}, author = {Myers, JE}, title = {Merchant Marine is not such a strange place for asbestos exposure.}, journal = {American journal of industrial medicine}, volume = {21}, number = {3}, pages = {457}, doi = {10.1002/ajim.4700210319}, pmid = {1585954}, issn = {0271-3586}, mesh = {Asbestos/*adverse effects ; Humans ; Male ; Mesothelioma/*etiology ; *Military Personnel ; Occupational Exposure/*adverse effects ; }, } @article {pmid1580262, year = {1992}, author = {Chellini, E and Fornaciai, G and Merler, E and Paci, E and Costantini, AS and Silvestri, S and Zappa, M and Buiatti, E}, title = {Pleural malignant mesothelioma in Tuscany, Italy (1970-1988): II. Identification of occupational exposure to asbestos.}, journal = {American journal of industrial medicine}, volume = {21}, number = {4}, pages = {577-585}, doi = {10.1002/ajim.4700210413}, pmid = {1580262}, issn = {0271-3586}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Asbestos/adverse effects ; Female ; Humans ; Italy/epidemiology ; Male ; Mesothelioma/chemically induced/*epidemiology ; Middle Aged ; *Occupational Exposure ; Pleural Neoplasms/chemically induced/*epidemiology ; }, abstract = {Following the finding of an unexpected cluster of mesotheliomas in textile workers, a surveillance system of malignant mesotheliomas was implemented in the region of Tuscany, Italy. This article reports on the investigation of 124 cases of mesothelioma diagnosed and reviewed by the Institutes of Morbid Anatomy and Histopathology at the Universities of Florence, Pisa, and Siena between 1970 and 1988. A complete occupational and asbestos exposure history was assessed through a semi-structured questionnaire directly administered to resident cases of Tuscany or, if deceased, to their closest living relatives, for a total of 100 interviews. The hypothesis of past occupational asbestos exposure was verified and documented. Seventy-two cases have been classified as occupationally exposed to asbestos; four were classified in the category of "possible domestic" exposure to asbestos. For two others, the role of other risk factors was stressed, and for 22 cases, either no asbestos exposure was found or the available data were not adequate to define it. The present study allowed identification of some unknown or scarcely known occupational asbestos exposures in the study area.}, } @article {pmid1536158, year = {1992}, author = {Walker, C and Everitt, J and Barrett, JC}, title = {Possible cellular and molecular mechanisms for asbestos carcinogenicity.}, journal = {American journal of industrial medicine}, volume = {21}, number = {2}, pages = {253-273}, doi = {10.1002/ajim.4700210214}, pmid = {1536158}, issn = {0271-3586}, mesh = {Animals ; Asbestos/*adverse effects/metabolism ; Carcinoma, Bronchogenic/*etiology/genetics ; Cell Transformation, Neoplastic/chemically induced/genetics ; Chromosome Aberrations/chemically induced ; Chromosome Disorders ; Cricetinae ; Growth Substances/metabolism ; Humans ; Mesocricetus ; Mesothelioma/*etiology/genetics ; Mutation ; Oxidants/metabolism ; Rats ; Smoking/adverse effects/metabolism ; }, abstract = {Asbestos fibers may exert their carcinogenic effects on mesothelial cells and bronchial epithelial cells by direct and indirect mechanisms. Direct effects can occur following the physical interaction of fibers with target cells or by the generation of free radicals from the fiber surface; indirect effects, following the interaction of fibers with inflammatory cells can result in the production of cellular mediators such as cytokines and various reactive oxygen species. As a result, target cells may be induced to proliferate and/or sustain genetic alterations, which lead to tumor development.}, } @article {pmid1519631, year = {1992}, author = {Schepers, GW}, title = {Re: "Changing attitudes and opinions: asbestos and cancer 1934-1965".}, journal = {American journal of industrial medicine}, volume = {22}, number = {3}, pages = {461-466}, doi = {10.1002/ajim.4700220323}, pmid = {1519631}, issn = {0271-3586}, mesh = {Asbestos/adverse effects/*history ; Asbestosis/complications/*history ; Attitude to Health ; Canada ; England ; History, 20th Century ; Humans ; Lung Neoplasms/etiology/*history ; Mesothelioma/etiology/*history ; Occupational Health/history/legislation & jurisprudence ; Pleural Neoplasms/etiology/*history ; Research ; Risk Factors ; South Africa ; United States ; }, } @article {pmid1519626, year = {1992}, author = {Bignon, J}, title = {How are we going to change our attitudes and opinions regarding asbestos and cancer in the next 20 years?.}, journal = {American journal of industrial medicine}, volume = {22}, number = {3}, pages = {443-446}, doi = {10.1002/ajim.4700220318}, pmid = {1519626}, issn = {0271-3586}, mesh = {Asbestos/*adverse effects ; *Attitude to Health ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Pleural Neoplasms/*etiology ; Risk Factors ; }, } @article {pmid1519624, year = {1992}, author = {Keane, J}, title = {Re: "Changing attitudes and opinions regarding asbestos and cancer 1934-1965".}, journal = {American journal of industrial medicine}, volume = {22}, number = {3}, pages = {429-433}, doi = {10.1002/ajim.4700220315}, pmid = {1519624}, issn = {0271-3586}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Asbestosis/*history ; Attitude to Health ; Chicago ; History, 20th Century ; Humans ; Lung Neoplasms/etiology/*history ; Mesothelioma/etiology/*history ; Middle Aged ; Peritoneal Neoplasms/etiology/*history ; Pleural Neoplasms/etiology/*history ; Research ; }, } @article {pmid1499621, year = {1992}, author = {Serio, G and Ceppi, M and Fonte, A and Martinazzi, M}, title = {Malignant mesothelioma of the testicular tunica vaginalis.}, journal = {European urology}, volume = {21}, number = {2}, pages = {174-176}, doi = {10.1159/000474830}, pmid = {1499621}, issn = {0302-2838}, mesh = {Aged ; Asbestos/*adverse effects ; Humans ; Immunoenzyme Techniques ; Male ; Mesothelioma/chemistry/etiology/*pathology ; Occupational Exposure ; Testicular Neoplasms/chemistry/etiology/*pathology ; Testis/*pathology ; }, abstract = {The histological, histochemical and immunohistochemical features of a malignant mesothelioma of the tunica vaginalis testis in a 69-year-old patient are described. The mesothelial derivation of the tumor was confirmed using a panel of selected antibodies. Malignant mesothelioma of the testicular tunica vaginalis is a rare tumor that must be considered so that appropriate treatment can be instituted.}, } @article {pmid1493265, year = {1992}, author = {Müller, KM}, title = {[Mesothelioma of the pleura--pathological anatomy].}, journal = {Langenbecks Archiv fur Chirurgie. Supplement. Kongressband. Deutsche Gesellschaft fur Chirurgie. Kongress}, volume = {}, number = {}, pages = {164-172}, pmid = {1493265}, issn = {0942-2854}, mesh = {Asbestosis/pathology ; Cell Transformation, Neoplastic/pathology ; Humans ; Mesothelioma/*pathology ; Pleura/pathology ; Pleural Neoplasms/*pathology ; }, abstract = {The examination of the pathology of diffuse malignant mesotheliomas (DMM) is based upon the analysis of 600 pleural tumours of the German Mesothelioma Panel in Bochum. Macroscopically there is a characteristic feature of the tumour growth, often restricted to the pleura, with preference of the basal pleural parts even in advanced stages. The highly variable growth pattern of the tumour phenotype contains parts of epithelial cells (42%), sarcoma-like cells (18%), and biphasic patterns (27%) as revealed by microscopy. Secondary pleural carcinosis are much more frequent (10 x) as diffuse malignant mesotheliomas but may mimic the DMM. Since there is no specific tumour marker for DMM available, additional immunohistochemical staining using different monoclonal antibodies directed against cytokeratins and epithelial antigens are recommended especially for examinations of small biopsies. The morphological security cheque follows the criteria of the European Mesothelioma Panel and is subdivided into 5 groups: A, assured mesothelioma; B, possible mesothelioma; C, probable mesothelioma; D, possibly no mesothelioma; E, certainly no mesothelioma. In the Bochum panel the incidence of A and B is 66%, of C, 6% and of D and E, 28%. In addition to the histomorphological examinations, in dust analysis of nontumourous lung tissue an augmented asbestos charge has been found in approximately 90% of all cases. The significance of asbestos fibers as an essential cause of the pleural mesothelioma could be underlined by our own animal experiments. After instillation of asbestos fibers into the right lung, a transpleural transport of fibers was observed with preneoplastic lesions and transformation of multipotent subserosal cells.}, } @article {pmid1489362, year = {1992}, author = {Gee, JB}, title = {Asbestos: the turbulent interface between science and policy.}, journal = {CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne}, volume = {146}, number = {1}, pages = {14-15}, pmid = {1489362}, issn = {0820-3946}, mesh = {Asbestosis/*complications ; Clinical Trials as Topic ; *Health Policy ; Humans ; Lung Neoplasms/*etiology ; Maximum Allowable Concentration ; Mesothelioma/*etiology ; Research Design ; }, } @article {pmid1442787, year = {1992}, author = {Giarelli, L and Bianchi, C and Grandi, G}, title = {Malignant mesothelioma of the pleura in Trieste, Italy.}, journal = {American journal of industrial medicine}, volume = {22}, number = {4}, pages = {521-530}, doi = {10.1002/ajim.4700220407}, pmid = {1442787}, issn = {0271-3586}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestosis/mortality/pathology ; Autopsy/statistics & numerical data ; Cross-Sectional Studies ; Female ; Follow-Up Studies ; Humans ; Incidence ; Italy/epidemiology ; Male ; Mesothelioma/*mortality/pathology ; Middle Aged ; Occupational Diseases/*mortality/pathology ; Occupational Exposure/adverse effects/*statistics & numerical data ; Occupations/statistics & numerical data ; Pleural Neoplasms/*mortality/pathology ; Risk Factors ; }, abstract = {One hundred and seventy malignant pleural mesotheliomas seen at necropsy at the Institute of Pathological Anatomy of the Trieste University during the period 1968-1987 were reviewed. The series included 153 men and 17 women, aged between 33 and 92 years (median 70 years). Lifetime work histories were obtained from the patients' relatives by personal or telephone interviews in 162 cases. A majority of the male subjects had been employed in "naval" work, 99 people having worked in the ship-building industry, 19 in the navy and merchant marine, and 7 in docks. A variety of trades appeared in the remaining histories. Work histories were indicative of occupational exposure to asbestos in 150 cases. A further 5 patients with negative or insufficient data showed asbestos bodies in routine lung sections and 5 women had a history of domestic exposure. A majority of the patients had had their first exposure before 1950. The intervals between first exposure and death ranged from 14 to 71 years (median 48 years).}, } @article {pmid1442785, year = {1992}, author = {Selikoff, IJ}, title = {Influence of age at death on accuracy of death certificate disease diagnosis: findings in 475 consecutive deaths of mesothelioma among asbestos insulation workers and asbestos factory workers.}, journal = {American journal of industrial medicine}, volume = {22}, number = {4}, pages = {505-510}, doi = {10.1002/ajim.4700220405}, pmid = {1442785}, issn = {0271-3586}, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Asbestosis/complications/*mortality ; Canada/epidemiology ; *Cause of Death ; *Death Certificates ; Humans ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; Middle Aged ; Occupational Diseases/*mortality ; Peritoneal Neoplasms/*mortality ; Pleural Neoplasms/*mortality ; Risk Factors ; United States/epidemiology ; }, } @article {pmid1442784, year = {1992}, author = {Selikoff, IJ}, title = {Death certificates in epidemiological studies, including occupational hazards: inaccuracies in occupational categories.}, journal = {American journal of industrial medicine}, volume = {22}, number = {4}, pages = {493-504}, doi = {10.1002/ajim.4700220404}, pmid = {1442784}, issn = {0271-3586}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asbestosis/*mortality ; Canada/epidemiology ; *Cause of Death ; Cohort Studies ; *Death Certificates ; Follow-Up Studies ; Humans ; Lung Neoplasms/mortality ; Male ; Mesothelioma/mortality ; Middle Aged ; Neoplasms/*mortality ; Occupational Diseases/classification/*mortality ; Occupational Exposure/adverse effects/*statistics & numerical data ; Occupations/*classification/statistics & numerical data ; Peritoneal Neoplasms/mortality ; Pleural Neoplasms/mortality ; Risk Factors ; Survival Analysis ; United States/epidemiology ; }, abstract = {We compared death certificates for asbestos-associated diseases (mesothelioma, lung cancer, asbestosis) in two asbestos workers' cohorts. One (insulation workers) had current or recent employment and a strong, continuing union support system which gave them much information about the effects of asbestos exposure. The second cohort, asbestos factory workers, had no such advantage. The factory had closed almost 30 years before, and its workers had dispersed into many areas of the state and nation. Accuracy of medical diagnosis was comparable in the two groups, but occupational listings were not. Three-quarters of the insulators' death certificates told of asbestos work, while virtually none of the factory workers' certificates provided such information, even for deaths of mesothelioma and asbestosis. The data indicate that disease categories, based on medical and pathological diagnoses, at least for asbestos-associated disease, tend to be accurate. Attempts to identify groups at risk by sorting occupational categories can give variable results, good for those with current exposures, much less satisfactory for those with long-past occupational exposures.}, } @article {pmid1442783, year = {1992}, author = {Selikoff, IJ and Seidman, H}, title = {Use of death certificates in epidemiological studies, including occupational hazards: variations in discordance of different asbestos-associated diseases on best evidence ascertainment.}, journal = {American journal of industrial medicine}, volume = {22}, number = {4}, pages = {481-492}, doi = {10.1002/ajim.4700220403}, pmid = {1442783}, issn = {0271-3586}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asbestosis/complications/*mortality ; Canada/epidemiology ; *Cause of Death ; Cohort Studies ; *Death Certificates ; Gastrointestinal Neoplasms/mortality ; Humans ; Kidney Neoplasms/mortality ; Lung Neoplasms/mortality ; Mesothelioma/mortality ; Middle Aged ; Neoplasms/*mortality ; Occupational Diseases/*mortality ; Occupational Exposure/adverse effects/*statistics & numerical data ; Pleural Neoplasms/mortality ; Prospective Studies ; Risk Factors ; Survival Analysis ; United States/epidemiology ; }, abstract = {There is extensive information on discordance in general between accuracy of medical diagnoses on death certificate categorization of cause of death and available clinical and histopathological data. This is as true for occupational disease as for other conditions. But occupational illnesses bear a special problem. Discordance is not equal across the board--it may vary with each occupationally related disease, and no single formula can be applied. It may be high for angiosarcoma and low for acute hydrogen sulfide poisoning, low for bladder cancer, high for unsuspected methyl mercury poisoning. We have found that for one agent--asbestos--there were different rates of discordance for different asbestos-related diseases (e.g., lung cancer, mesothelioma, asbestosis, kidney cancer) among 4,951 deaths studied prospectively from 1967 to 1986. Caution is therefore required before accepting generalizations concerning (unstudied) discordance in occupational mortality studies, and in their use in risk assessment models.}, } @article {pmid1439223, year = {1992}, author = {Tammilehto, L and Maasilta, P and Kostiainen, S and Appelqvist, P and Holsti, LR and Mattson, K}, title = {Diagnosis and prognostic factors in malignant pleural mesothelioma: a retrospective analysis of sixty-five patients.}, journal = {Respiration; international review of thoracic diseases}, volume = {59}, number = {3}, pages = {129-135}, doi = {10.1159/000196043}, pmid = {1439223}, issn = {0025-7931}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Mesothelioma/*diagnosis/mortality/pathology/secondary/therapy ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Pleural Neoplasms/*diagnosis/mortality/pathology/therapy ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Survival Rate ; }, abstract = {This report is an analysis of the medical records of 83 patients registered between 1960 and 1980 at Helsinki University Central Hospital as having malignant pleural mesothelioma. 65 of 83 patients had histologically confirmed malignant mesothelioma, and are the focus of this analysis. The remaining 18 (22%) patients were excluded because malignant mesothelioma was only confirmed cytologically, or because the primary tumor was not a mesothelioma. The ratio of men to women was 2:1.30 of 65 (46%) patients were not known or not likely to have been exposed to asbestos. The main symptoms at presentation were dyspnea, cough, chest pain, fatigue and weight loss. The median survival from diagnosis was 12 months, and from the onset of symptoms 18 months. Clinical stage and performance status were significant prognostic factors. Hematogenous metastases were present at autopsy in most cases. Disease and performance status therefore need to be well established and documented in clinical trials involving mesothelioma.}, } @article {pmid1415291, year = {1992}, author = {Huuskonen, MS and Tossavainen, A}, title = {Fifty-year experience in diagnosing asbestos-related cancers in Finland: progress and detours.}, journal = {American journal of industrial medicine}, volume = {22}, number = {2}, pages = {259-261}, doi = {10.1002/ajim.4700220211}, pmid = {1415291}, issn = {0271-3586}, mesh = {Asbestos/adverse effects ; Asbestosis/*history ; Finland ; History, 20th Century ; Humans ; Lung Neoplasms/*history ; Mesothelioma/history ; Occupational Diseases/history ; }, } @article {pmid1415286, year = {1992}, author = {Murai, Y and Kitagawa, M}, title = {Asbestos fiber analysis in 27 malignant mesothelioma cases.}, journal = {American journal of industrial medicine}, volume = {22}, number = {2}, pages = {193-207}, doi = {10.1002/ajim.4700220206}, pmid = {1415286}, issn = {0271-3586}, mesh = {Adult ; Aged ; Asbestos/*analysis ; Electron Probe Microanalysis ; Female ; Humans ; Male ; Mesothelioma/chemistry/*pathology ; Middle Aged ; Peritoneal Neoplasms/chemistry/*pathology ; Pleural Neoplasms/chemistry/*pathology ; }, abstract = {The asbestos body counts per 5 gm wet lung tissue in 27 (23 pleural and 4 peritoneal) malignant mesothelioma cases derived from 19 autopsy and 8 surgical cases were, according to our own criteria, low level exposure in 13 cases (48.2%), moderate level exposure in 2 cases (7.4%), and high level exposure in 12 cases (44.4%). In our previous study on 235 consecutive autopsy cases, the low level exposure was considered to be environmental, the moderate level was secondary or blue collar, and the high level was occupational. In the present study, about half of the cases examined (44.4%, high level exposure) are closely related to some occupational asbestos exposure and the other half (48.2%) to environmental exposure. The type and size of asbestos fibers from the 12 cases of high level exposure were analyzed and the characteristics were compared with those of cases of low level exposure without lung cancer or mesothelioma. Most fibers analyzed (98%) were longer than 5 microns and thicker than 0.10 micron by our counting rules. In the control group, predominant fibers were tremolite or actinolite. In all the 11 pleural mesothelioma cases, the content of amosite fibers was significantly higher than in the controls. In one case of peritoneal mesothelioma, incipient asbestosis was found and the predominant fibers were crocidolite. It is suggested that the presence of amosite and crocidolite is linked to mesothelioma. The mean lengths of amosite and crocidolite, as detected by our resolution capabilities, were 36.0 and 20.9 microns, and the mean diameters were 0.51 and 0.27 micron, respectively. Both amosite and crocidolite fibers had high aspect ratios (94.2 and 115.4).}, } @article {pmid1411371, year = {1992}, author = {Huuskonen, MS}, title = {Screening for occupational cancer.}, journal = {Scandinavian journal of work, environment & health}, volume = {18 Suppl 1}, number = {}, pages = {110-114}, pmid = {1411371}, issn = {0355-3140}, mesh = {Asbestos/adverse effects ; Finland ; Humans ; Lung Neoplasms/etiology/*prevention & control ; *Mass Screening ; Mesothelioma/etiology/*prevention & control ; Occupational Diseases/etiology/*prevention & control ; Pleural Neoplasms/etiology/*prevention & control ; Precancerous Conditions/etiology/*prevention & control ; }, abstract = {The main strategy for preventing occupational cancer is an environmentally based approach or primary prevention. However, it should be combined with screening, early diagnosis, and treatment. This review discusses screening for occupational cancer but not from the point of view of medical screening. Instead it focuses on asbestos exposure and asbestos-related cancer in Finland and the role screening plays in the current Finnish asbestos program. For example it is the feeling in Finland that screening is a very effective way of preventing further occupational exposure to asbestos and of organizing antismoking campaigns. An individually oriented strategy in cancer prevention should include the modification of exposures by behavioral change, the monitoring of early effects of exposures, and health examinations. The termination of exposure, antismoking campaigns, improved diagnostics, and careful attention to compensation issues combined with the study of other opportunities for prevention are seen as the key issues in screening.}, } @article {pmid1387761, year = {1992}, author = {Morgan, RW}, title = {Attitudes about asbestos and lung cancer.}, journal = {American journal of industrial medicine}, volume = {22}, number = {3}, pages = {437-441}, doi = {10.1002/ajim.4700220317}, pmid = {1387761}, issn = {0271-3586}, mesh = {Asbestos/*adverse effects ; Asbestosis/epidemiology ; Attitude to Health ; Humans ; Lung Neoplasms/epidemiology/*etiology ; Mesothelioma/epidemiology/*etiology ; Meta-Analysis as Topic ; Research ; Risk Factors ; Smoking/adverse effects ; }, } @article {pmid1337830, year = {1992}, author = {Kishimoto, T}, title = {Coexistence of a malignant fibrous histiocytoma and asbestos exposure. Brief report.}, journal = {Pathobiology : journal of immunopathology, molecular and cellular biology}, volume = {60}, number = {6}, pages = {332-334}, doi = {10.1159/000163745}, pmid = {1337830}, issn = {1015-2008}, mesh = {Asbestos/*adverse effects/analysis ; Histiocytoma, Benign Fibrous/chemistry/*etiology/pathology ; Humans ; Lung/chemistry/diagnostic imaging/pathology ; Lung Neoplasms/chemistry/*etiology/pathology ; Male ; Middle Aged ; Occupational Diseases/etiology/pathology ; Radiography ; }, abstract = {A 59-year-old male died of malignant fibrous histiocytoma. He had a history of asbestos exposure as a shipfitter in the Japanese Naval Shipyard and other shipyards for 45 years. Numerous asbestos bodies were detected in the autopsied lung and within the lesion. X-ray analysis of the asbestos fibers showed them to be crocidolite, a type of asbestos fiber commonly seen in association with mesothelioma and other types of cancer. This case adds malignant fibrous histiocytoma to the growing number of tumors that can be attributed etiologically to asbestos exposure.}, } @article {pmid1334373, year = {1992}, author = {Harington, JS}, title = {Mesothelioma among workers in the Québec chrysotile mining and milling industry.}, journal = {American journal of industrial medicine}, volume = {22}, number = {6}, pages = {925-926}, doi = {10.1002/ajim.4700220612}, pmid = {1334373}, issn = {0271-3586}, mesh = {Asbestos/*adverse effects ; Asbestos, Serpentine ; Humans ; Mesothelioma/*mortality ; *Mining ; Occupational Diseases/*mortality ; Quebec/epidemiology ; Survival Rate ; }, } @article {pmid1332468, year = {1992}, author = {Levin, JL and Stocks, JM and Shepherd, JR and Fagan, MF and Dodson, RF}, title = {Asbestos exposures: known and underrecognized sources.}, journal = {American journal of industrial medicine}, volume = {22}, number = {4}, pages = {607-608}, doi = {10.1002/ajim.4700220415}, pmid = {1332468}, issn = {0271-3586}, mesh = {Asbestos/*adverse effects ; Asbestos, Serpentine ; Asbestosis/*etiology ; Humans ; *Laundering ; Mesothelioma/*etiology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*etiology ; *Welding ; }, } @article {pmid1332466, year = {1992}, author = {Bégin, R and Gauthier, JJ and Desmeules, M and Ostiguy, G}, title = {Work-related mesothelioma in Québec, 1967-1990.}, journal = {American journal of industrial medicine}, volume = {22}, number = {4}, pages = {531-542}, doi = {10.1002/ajim.4700220408}, pmid = {1332466}, issn = {0271-3586}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Asbestos, Serpentine ; Asbestosis/mortality/pathology ; Biopsy ; Cross-Sectional Studies ; Humans ; Incidence ; Male ; Mesothelioma/*epidemiology/pathology ; Middle Aged ; Mining/statistics & numerical data ; Occupational Diseases/*epidemiology/pathology ; Occupational Exposure/adverse effects/*statistics & numerical data ; Pleura/pathology ; Pleural Neoplasms/*epidemiology/pathology ; Quebec/epidemiology ; Risk Factors ; }, abstract = {Prior surveys of malignant mesothelioma in Québec have noted that almost all the excess in occupational exposure related mesothelioma was in the manufacture and industrial application of asbestos rather than in the mining and milling operations. To evaluate the current status of malignant pleural mesothelioma in the Québec workforce, we reviewed all cases of pleural mesothelioma seen and accepted by the Québec Workman's Compensation Board (CSST) for work related compensation of industrial disease. We identified 120 cases, 7 of whom were females. They were of an average age of 59 +/- 8.5 yrs (sd) (range 42-84); they were exposed to asbestos dust in the workplace for an average of 26 +/- 14.3 yrs (range 0.5-50). The cases were subdivided into 3 groups according to workplace asbestos exposures. There were 49 cases originating in the mines and mills of the Québec Eastern Township region (primary industry, group 1), 50 cases from the manufacture and industrial application sector (secondary industry, group 2), and 21 cases from industries where asbestos was not a major work material, often an "incidental" material (tertiary industry, group 3). Group 1 was of an average age of 62 +/- 8 years, exposed to asbestos dust 31 +/- 14 years and the distribution of exposure time was as follows: 15% cases with < or = 10 year-exposure and 77% > or = 25 year-exposure. In group 2, the age was significantly lower at 57 +/- 9 years; the exposure time was also significantly lower at 22 +/- 14 years, and the distribution of exposure time differed from the above (29% cases with < or = 10 year-exposure and 48% > or = 25 year-exposure). In group 3, the average age was 58 +/- 7 years, the exposure time was also significantly lower at 28 +/- 12 years and the distribution of exposure time differed from the above (33% cases with < or = 10 year-exposure and 62% > or = 25 year-exposure). Analyses of the yearly incidence of new cases in each group documented the general incremental trend in all groups, with the sharpest rises in group 3. In the mining towns of Thetford and Asbestos, the incidence of mesothelioma was proportional to the workforce, thus suggesting that the tremolite air contamination, which is 7.5 x higher in Thetford, may not be a significant determinant of the disease in these workers.(ABSTRACT TRUNCATED AT 400 WORDS)}, } @article {pmid1329506, year = {1992}, author = {Friedrichs, KH and Brockmann, M and Fischer, M and Wick, G}, title = {Electron microscopy analysis of mineral fibers in human lung tissue.}, journal = {American journal of industrial medicine}, volume = {22}, number = {1}, pages = {49-58}, doi = {10.1002/ajim.4700220105}, pmid = {1329506}, issn = {0271-3586}, mesh = {Analysis of Variance ; Asbestos/analysis ; Asbestos, Amphibole ; Asbestos, Serpentine ; Asbestosis/metabolism ; Electron Probe Microanalysis ; Environmental Pollutants/analysis ; Humans ; Lung/*chemistry ; Lung Neoplasms/chemistry ; Mesothelioma/chemistry ; Minerals/*analysis ; Silicon Dioxide/analysis ; }, abstract = {In the present study, lung samples from 126 autopsied cases were examined to determine the content of mineral fibers using analytical transmission electron microscopy (ATEM). The cases were divided into four groups (22 lungs of persons exposed to ambient environmental pollution, 32 cases of mesothelioma, 38 cases of primary lung cancer, and 34 asbestosis cases, 13 of these with additional pleural plaques). Fibers were counted, measured, and mineralogically identified using a combination of X-ray microanalysis and electron diffraction of the non-oriented fiber. Concentration of fibrous particles (defined as particles above 1 micron in length with roughly parallel long sides and an aspect ratio of 5:1 and greater) was calculated as fibers 10(6)/g dry lung weight. The concentration of chrysotile was found to be similar throughout the groups except for two cases in the asbestosis group with comparably high numbers of chrysotile. However, a remarkable difference for amphiboles could be observed between the groups. Asbestos bodies were mostly found in the asbestosis group. There was a rather good correlation between numbers of amphibole fibers and asbestos bodies, with an average ratio of 10:1. For comparison purposes between occupationally exposed/non-exposed individuals, a transition was found in the concentration range of 3-10(7) asbestos fibers/g dried lung weight.}, } @article {pmid1328810, year = {1992}, author = {Woźniak, H and Wiecek, E and Stetkiewicz, J and Lao, I and Krajnow, A and Roszkowicz, A}, title = {[Asbestos substitutes and their biological effects. 3. Carcinogenic effects of synthetic amphiboles in animal experiments].}, journal = {Medycyna pracy}, volume = {43}, number = {3}, pages = {257-266}, pmid = {1328810}, issn = {0465-5893}, mesh = {Animals ; Asbestos/administration & dosage/*adverse effects ; Asbestos, Crocidolite ; Asbestos, Serpentine ; Cobalt/administration & dosage/*adverse effects ; *Disease Models, Animal ; Female ; Injections, Intraperitoneal ; Magnesium/administration & dosage/*adverse effects ; Male ; Mesothelioma/chemically induced/*etiology ; Nickel/administration & dosage/*adverse effects ; Peritoneal Neoplasms/chemically induced/*etiology ; Rats ; Rats, Wistar ; }, abstract = {This work presents the results of the test performed on rats to evaluate the carcinogenic effect of 4 synthetic amphiboles compared to that of the natural amphibole--crocidolite. The dose of the magnesium amphibole (Na2Mg6Si8(OH)2) administered to the animals contained 240 x 10(6) respirable fibres; the corresponding value for the nickel amphibole (Na2Ni6Si8O22(OH)2) was 339 x 10(6), for the cobalt amphibole (Na2Co6Si8O22(OH)2)--1000 x 16(6) for the geranium amphibole (Na2Mg6Ge8(OH)2)--250 x 10(6), and of the natural crocidolite amphibole (Na2Fe2Fe3Si8O22(OH)2) x 380 x 10(6) respirable fibres. The control animals (rats) received physiological NaCl solution. The number of peritoneal mesotheliomas following single intraperitoneal administration of 20 mg of the dust was adapted to be the measure of the carcinogenic activity of the dust. 3 synthetic (magnesium, cobalt and nickel) amphiboles and crocidolite caused development of malignant peritoneal mesothelioma in 11.1% to 71% rats. The results show that there is a relationship between the chemical composition of the synthetic amphiboles and their carcinogenic effect. Out of 4 investigated synthetic amphiboles, the magnesium amphibole, which contained magnesium and silicon, displayed most severe carcinogenic effect. The synthetic amphiboles containing either silicon and cobalt or silicon and nickel displayed 8.3 and 6.2 times weaker ability to induce peritoneal mesothelioma.}, } @article {pmid1328809, year = {1992}, author = {Wiecek, E and Szczepaniak, M and Bielichowska-Cybula, G and Woźniak, H}, title = {[Asbestos substitutes and their biological effects. 2. Synthetic amphiboles--their physico-chemical characteristics].}, journal = {Medycyna pracy}, volume = {43}, number = {3}, pages = {251-256}, pmid = {1328809}, issn = {0465-5893}, mesh = {Asbestos/*adverse effects/analysis ; Asbestos, Crocidolite ; Asbestosis/*etiology ; Cobalt/*adverse effects/analysis ; Humans ; Lung Neoplasms/chemically induced/*etiology ; Magnesium/*adverse effects/analysis ; Mesothelioma/chemically induced/*etiology ; Microscopy, Electron ; Nickel/*adverse effects/analysis ; Particle Size ; X-Ray Diffraction ; }, abstract = {Metal content in the chemical structure of asbestos and man-made mineral fibres can affect their carcinogenic properties. As the chemical composition (metal content) of man-made silicate substitutes for asbestos can be varied almost at will in the process of their manufacture, the search for potentially least carcinogenic silicates appears to be of utmost importance. This paper presents diffractometric characteristics, dimensional analysis and morphology data for 4 synthetic amphibole fibres with chemical compositions differing from that of natural crocidolite amphibole. Those included the following synthetic amphiboles: Na2Mg6Ge8O22(OH)2; Na2Ni6Si8O22(OH)2; Na2Mg6Si8O22(OH)2; Na2Co6Si8O22(OH)2. The studied amphiboles differed in fibre length and diameter. The magnesium amphibole contained the longest (6.03 microns) fibres, and the nickel amphibole contained the shortest (2.7 microns) fibres, resembling those of crocidolite. The highest content (54.7%) of respirable fibres was found in the magnesium amphibole, and the lowest (15.9%) in the natural crocidolite. The authors suggest that the detected differences in the physical and chemical characteristics of the synthetic amphiboles may affect their biological properties.}, } @article {pmid1325175, year = {1992}, author = {Tammilehto, L and Tuomi, T and Tiainen, M and Rautonen, J and Knuutila, S and Pyrhönen, S and Mattson, K}, title = {Malignant mesothelioma: clinical characteristics, asbestos mineralogy and chromosomal abnormalities of 41 patients.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {28A}, number = {8-9}, pages = {1373-1379}, doi = {10.1016/0959-8049(92)90523-5}, pmid = {1325175}, issn = {0959-8049}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Asbestos, Amosite ; *Asbestos, Amphibole ; Asbestos, Crocidolite ; *Chromosome Aberrations ; *Chromosome Disorders ; *Chromosomes, Human, Pair 7 ; Female ; Humans ; Karyotyping ; Male ; Mesothelioma/*genetics/mortality/pathology ; Middle Aged ; Pleural Neoplasms/*genetics/mortality/pathology ; Prognosis ; Sex Factors ; }, abstract = {The clinical characteristics and the results of mineral fibre and cytogenetic analyses were coordinated prospectively for 41 patients with confirmed malignant pleural mesothelioma. A correlation was found between high total fibre concentration, and partial or total loss of chromosomes 1, 4 and 9 and chromosomal rearrangements involving a breakpoint at 1p11-p22. There was also a correlation between crocidolite/amosite as the main fibre type and partial or total loss of chromosomes 1, 3 and 4 and chromosomal rearrangements involving del (3p). Positive prognostic factors were female gender, low total fibre concentration (less than 10(6) fibres per g dried lung tissue), anthophyllite as the main fibre type and normal chromosome 7. In addition, we found 4 patients with malignant mesothelioma who had been exposed mainly to anthophyllite fibres (total lung fibre concentrations of 1.2, 0.4, 0.2 and 0.1 x 10(6) fibres per g dried lung tissue). This would seem to indicate that there may be a carcinogenic role for anthophyllite.}, } @article {pmid1324961, year = {1992}, author = {Luo Sugiong, Q and Liu Xueze, Z and Wang Chaojun, J}, title = {An investigation of crocidolite contamination and experimental study in southwestern China.}, journal = {Journal of hygiene, epidemiology, microbiology, and immunology}, volume = {36}, number = {2}, pages = {223-224}, pmid = {1324961}, issn = {0022-1732}, mesh = {Adult ; Aged ; Animals ; Asbestos/chemistry/*toxicity ; Asbestos, Crocidolite ; Asbestosis/*epidemiology ; China/epidemiology ; Female ; Humans ; Lung Neoplasms/chemically induced ; Male ; Mesothelioma/chemically induced ; Middle Aged ; Prevalence ; Rats ; Risk Factors ; }, } @article {pmid1323229, year = {1992}, author = {Merler, E and Chellini, E}, title = {[Epidemiology of primary tumors of the pleura].}, journal = {Annali dell'Istituto superiore di sanita}, volume = {28}, number = {1}, pages = {133-146}, pmid = {1323229}, issn = {0021-2571}, mesh = {Asbestos/adverse effects ; Asbestos, Amosite ; Asbestos, Crocidolite ; Asbestos, Serpentine ; Asbestosis/complications/epidemiology ; Construction Materials/statistics & numerical data ; Europe/epidemiology ; Female ; Humans ; Italy/epidemiology ; Lung Neoplasms/epidemiology/etiology ; Male ; Mesothelioma/*epidemiology/etiology ; Occupational Diseases/epidemiology/etiology ; Pleural Neoplasms/*epidemiology/etiology ; Prevalence ; Risk Factors ; }, abstract = {The authors briefly reviewed the literature concerning the risk factors for primary pleural tumors in humans. The results from the most relevant studies emphasize the fact that the large majority of mesotheliomas are associated with exposure to asbestos or asbestiform fibers. Exposure to asbestos is mainly through industrial use, and mesotheliomas result from occupational, para-occupational, or environmental exposure. Fibers of crocidolite, amosite, and chrysotile appear to be, in descending order, more carcinogenic for pleural tissues. The authors summarize the available data on consumption of asbestos and asbestos-based products in Italy. The chrysotile-asbestos mine in Balangero (Piedmont) stimulated the industrial production of asbestos-cement; asbestos has been largely sprayed among shipyards and user for insulating railroad coaches and carriages. Italy had the greatest consumption of crocidolite in Europe, which was not banned until 1986. The authors discuss the major findings derived from descriptive epidemiological data presented in previous papers dealing with this issue. In addition, standardized mortality rates of primary pleural tumors for European countries are shown. A clearly increasing trend for mortality is observed in Italy, which has also the provinces with the highest mortality rates in Europe. Among Italian provinces, the mortality rates are consistent with the number of asbestosis cases receiving workman's compensation. The authors present the results of both cohort and case-control analytical studies performed in Italy, and provide suggestions for further research.}, } @article {pmid1316720, year = {1992}, author = {Wong, O}, title = {Chrysotile asbestos, mesothelioma, and garage mechanics.}, journal = {American journal of industrial medicine}, volume = {21}, number = {3}, pages = {449-455}, doi = {10.1002/ajim.4700210317}, pmid = {1316720}, issn = {0271-3586}, mesh = {Asbestos/*adverse effects ; Asbestos, Serpentine ; *Automobiles ; Humans ; Mesothelioma/epidemiology/*etiology ; Occupational Diseases/*etiology ; }, } @article {pmid1316719, year = {1992}, author = {Kern, DG and Hanley, KT and Roggli, VL}, title = {Malignant mesothelioma in the jewelry industry.}, journal = {American journal of industrial medicine}, volume = {21}, number = {3}, pages = {409-416}, doi = {10.1002/ajim.4700210313}, pmid = {1316719}, issn = {0271-3586}, mesh = {Air Pollutants, Occupational/analysis ; Asbestos/*adverse effects ; Asbestos, Amosite ; Asbestos, Serpentine ; Humans ; Lung Neoplasms/*chemically induced/pathology ; Male ; Mesothelioma/*chemically induced/pathology ; Middle Aged ; Occupational Diseases/*chemically induced/pathology ; }, abstract = {We conducted a clinical, environmental, pathologic, and mineral lung burden investigation of a 61-year-old man with malignant mesothelioma. For 35 years, up until three weeks prior to pneumonectomy, the patient made asbestos soldering forms at a costume jewelry production facility. Only chrysotile asbestos was used at the plant during the last decade of the patient's employment, and recent environmental sampling of the work-place identified no other asbestos fiber type. Anticipating that the patient would add to the very small number of cases of mesothelioma attributable solely to chrysotile, we found instead that the patient's lung tissue contained large numbers of both coated and uncoated amosite asbestos fibers but, surprisingly, no chrysotile. We subsequently learned that a distributor of both chrysotile and amosite supplied the company during the first 25 years the patient was fabricating soldering forms. The findings underscore the futility of estimating environmental exposure to chrysotile on the basis of fiber counts in lung tissue. Although we previously described non-neoplastic asbestos-related disease among patients engaged in similar work, this case, to the best of our knowledge, represents the first report of mesothelioma in the commercial jewelry industry. As such, it prompted us to initiate a public health campaign to replace asbestos soldering forms in this industry with readily available, safer alternatives.}, } @article {pmid1311147, year = {1992}, author = {Tuomi, T}, title = {Fibrous minerals in the lungs of mesothelioma patients: comparison between data on SEM, TEM, and personal interview information.}, journal = {American journal of industrial medicine}, volume = {21}, number = {2}, pages = {155-162}, doi = {10.1002/ajim.4700210205}, pmid = {1311147}, issn = {0271-3586}, mesh = {Adult ; Aged ; Asbestos/adverse effects/*classification/isolation & purification ; Asbestos, Amosite ; *Asbestos, Amphibole ; Asbestos, Crocidolite ; Female ; Finland ; Humans ; Male ; Mesothelioma/*etiology ; Microscopy, Electron ; Microscopy, Electron, Scanning ; Middle Aged ; Occupational Diseases/*etiology ; }, abstract = {To determine and compare the fiber types and size distributions in the lung tissue of mesothelioma patients in Finland, samples from 29 patients with known work history were analyzed with transmission electron microscopy (TEM) and X-ray microanalysis. Compared with the earlier results using scanning electron microscopy (SEM), the fiber concentrations were about three times as high and ranged from 0.1 million to 5,200 million fibers per gram of dry tissue. In 15 patients (52%), crocidolite/amosite were the dominating fiber types, representing more than 70% of all fibers. Anthophyllite asbestos was the most prevalent fiber type in eight patients (28%), and it was found in the samples of 13 patients (45%). One-half of the anthophyllite fibers were longer than 5 microns, whereas other fiber types were somewhat smaller.}, } @article {pmid1809178, year = {1991}, author = {Finkelstein, MM}, title = {Analysis of the exposure-response relationship for mesothelioma among asbestos-cement factory workers.}, journal = {Annals of the New York Academy of Sciences}, volume = {643}, number = {}, pages = {85-89}, doi = {10.1111/j.1749-6632.1991.tb24447.x}, pmid = {1809178}, issn = {0077-8923}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Cohort Studies ; Dose-Response Relationship, Drug ; Humans ; Lung Neoplasms/*epidemiology/etiology ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Diseases/*epidemiology/etiology ; Ontario ; Risk Factors ; }, } @article {pmid1809169, year = {1991}, author = {Anderson, HA and Hanrahan, LP and Schirmer, J and Higgins, D and Sarow, P}, title = {Mesothelioma among employees with likely contact with in-place asbestos-containing building materials.}, journal = {Annals of the New York Academy of Sciences}, volume = {643}, number = {}, pages = {550-572}, doi = {10.1111/j.1749-6632.1991.tb24506.x}, pmid = {1809169}, issn = {0077-8923}, support = {U53-CCU500801//PHS HHS/United States ; U60-CCU502984//PHS HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Air Pollution, Indoor/*adverse effects ; Asbestos/*adverse effects ; Construction Materials/*adverse effects ; Death Certificates ; Female ; Humans ; Maintenance ; Male ; Mesothelioma/*epidemiology/etiology/mortality ; Middle Aged ; Peritoneal Neoplasms/*epidemiology/etiology/mortality ; Pleural Neoplasms/*epidemiology/etiology/mortality ; Registries ; *Schools ; Wisconsin ; }, abstract = {The occurrence of mesothelioma is a sentinel event in occupational and environmental disease. A mesothelioma surveillance system was established utilizing existing computerized Wisconsin vital statistics data maintained since 1959 and a Cancer Reporting System (CRS) established in 1978. Review of the death certificate listing of usual occupation and industry from 487 mesothelioma deaths in Wisconsin from 1959 to 1989 led to the investigation of 41 persons with likely exposure to inplace asbestos-containing building materials (ACBM): 12 school teachers, 10 school maintenance employees, 7 public building maintenance workers, 5 private building maintenance workers, and 7 commercial and factory workers performing maintenance activities. For 10 (34%) of the 29 maintenance workers the only source of asbestos exposure identified was their maintenance work. For five (17%) histories indicated some prior employment in occupations and industries with probable asbestos exposures. Opportunities for indirect occupational exposure were identified for ten who had been employed in the residential construction industry. One maintenance worker was exposed to asbestos in the household and another had neighborhood exposure. For 9 (75%) of the school teachers, the only identifiable potential source of asbestos exposure was derived from in-place ACBM in schools. One teacher had spent a season in the merchant marine aboard an iron ore-hauling ship and 2 had worked in the residential construction industry. Two of the teachers were sisters, and in two instances, two teachers had taught in the same school facility. We conclude that individuals occupationally exposed to in-place ACBM are at risk for the subsequent development of mesothelioma.}, } @article {pmid1809164, year = {1991}, author = {Roggli, VL and Longo, WE}, title = {Mineral fiber content of lung tissue in patients with environmental exposures: household contacts vs. building occupants.}, journal = {Annals of the New York Academy of Sciences}, volume = {643}, number = {}, pages = {511-518}, doi = {10.1111/j.1749-6632.1991.tb24501.x}, pmid = {1809164}, issn = {0077-8923}, mesh = {Adult ; Aged ; Air Pollution, Indoor/*adverse effects ; Asbestos/*adverse effects ; Environmental Exposure ; Family ; Female ; Humans ; Male ; Mesothelioma/*etiology/pathology ; Middle Aged ; Peritoneal Neoplasms/*etiology/pathology ; Pleural Neoplasms/*etiology/pathology ; }, abstract = {Analysis of tissue mineral fiber content in patients with environmental exposures has seldom been reported in the past. Our studies of six household contacts of asbestos workers indicate that these individuals often have pulmonary asbestos concentrations similar to some occupationally exposed individuals. In contrast, our studies of four occupants of buildings with asbestos-containing materials indicate that these individuals often have pulmonary asbestos burdens indistinguishable from the general nonoccupationally exposed population. However, one such building occupant exposed for many years and who later developed pleural mesothelioma was studied in detail, and it was concluded that her exposure as a teacher's aide in a school building containing acoustical plaster was the likely cause of her mesothelioma.}, } @article {pmid1809162, year = {1991}, author = {Case, BW}, title = {Health effects of tremolite. Now and in the future.}, journal = {Annals of the New York Academy of Sciences}, volume = {643}, number = {}, pages = {491-504}, doi = {10.1111/j.1749-6632.1991.tb24498.x}, pmid = {1809162}, issn = {0077-8923}, mesh = {Animals ; *Asbestos, Amphibole ; *Carcinogens ; Humans ; Lung Neoplasms/*chemically induced/epidemiology ; Mesothelioma/*chemically induced/epidemiology ; *Mining ; Occupational Diseases/*chemically induced/epidemiology ; Particle Size ; Silicic Acid/*toxicity ; }, abstract = {Although tremolite asbestos has been well characterized since 1916, appreciation of its role in disease induction is relatively recent. It has always been understood that the morphology of tremolite is complex, and part of the slowness in recognizing it as a hazard has been definitional in nature. Reduced to simple terms the questions are, when is tremolite "asbestos-like," when is it an innocuous amorphous particle, do these forms occur together, with what confidence can they be separated for regulatory purposes, and what is the spectrum of disease potential for varying exposure? A brake on regulation is partially due to a convergence of opinion of unlikely and unintentional allies: industries producing tremolite-containing materials and some epidemiologists resisting attribution of risk to tremolite on the grounds that its known effects--pleural plaques, asbestosis, lung cancer and mesothelioma--are principally due to chrysotile, which is often contaminated with fibrous tremolite. The latter group concentrate their skepticism on internal-dose biomarker studies associating lung tremolite content with mesothelioma (but not so clearly with lung cancer or asbestosis). They ignore the basic carcinogenic quality of fibrous tremolite, shown in both animal and epidemiological studies. Evidence from the Quebec chrysotile/tremolite mining districts suggests that very low concentrations of tremolite in ambient air can be translated into high concentrations in lung, even in those without occupational exposure. Disease incidence, especially for mesothelioma, seems also to be associated with tremolite air and lung content. The risk associated with tremolite has been demonstrated in Corsica, Cyprus, the United States, and Canada. Of particular importance is an apparent increase in the proportion of mesothelioma risk attributable to tremolite, since the fibers heretofore most responsible for that disease--commercial amphiboles--have been or are being severely regulated or completely eliminated in production and use. Further, amosite and crocidolite, while still a concern, form a small fraction of "asbestos-in-place": most of this material is chrysotile and we do not really know to what degree it is contaminated with tremolite. The available evidence suggests that bulk analysis or airborne fiber analysis will not answer this question, and perhaps only animal bioaccumulation assay is sufficient. Until we know more, it seems prudent for public health to avoid dispersing chrysotile/tremolite into the environment, and, where we can, to regulate all tremolite "fibers" conservatively.}, } @article {pmid1809161, year = {1991}, author = {Davis, JM and Addison, J and McIntosh, C and Miller, BG and Niven, K}, title = {Variations in the carcinogenicity of tremolite dust samples of differing morphology.}, journal = {Annals of the New York Academy of Sciences}, volume = {643}, number = {}, pages = {473-490}, doi = {10.1111/j.1749-6632.1991.tb24497.x}, pmid = {1809161}, issn = {0077-8923}, mesh = {Animals ; *Asbestos, Amphibole ; *Carcinogens ; Dust ; Injections, Intraperitoneal ; Mesothelioma/*etiology ; Particle Size ; Peritoneal Neoplasms/*etiology ; Rats ; Silicic Acid/analysis/*toxicity ; }, abstract = {Six samples of tremolite of different morphological type were prepared as dusts of respirable size and used in intraperitoneal injection studies in rats. Three "asbestiform" tremolites produced mesotheliomas in almost all animals, although with significantly different tumor-induction periods. A brittle type of fibrous tremolite which, when manipulated to prepare "respirable dust," produced a sample with relatively few asbestiform fibers remaining nonetheless produced tumors in 70% of rats. Two samples of nonfibrous tremolite produced respirable dust samples containing numerous elongated fragments with aspect ratios greater than 3:1, which therefore fitted the definition of respirable fibers. Both these samples produced relatively few tumors, although one had more long "fibers" than did the brittle tremolite that produced 70% of tumors. This study has therefore demonstrated that different morphologic forms of tremolite produce dusts with very different carcinogenic potential. Carcinogenicity does not depend simply on the number of elongated particles injected, and we need to develop methods of distinguishing carcinogenic tremolite fibers from relatively innocuous tremolite dusts, with similar numbers of elongated particles of similar aspect ratios.}, } @article {pmid1809160, year = {1991}, author = {Harington, JS}, title = {The carcinogenicity of chrysotile asbestos.}, journal = {Annals of the New York Academy of Sciences}, volume = {643}, number = {}, pages = {465-472}, doi = {10.1111/j.1749-6632.1991.tb24496.x}, pmid = {1809160}, issn = {0077-8923}, mesh = {Animals ; Asbestos/*toxicity ; Carcinogens/*toxicity ; Cells, Cultured ; Environmental Exposure ; Humans ; Lung Neoplasms/epidemiology/*etiology ; Mesothelioma/epidemiology/*etiology ; }, abstract = {In in vitro test systems, chrysotile is markedly toxic, causes chromosomal aberrations, and is capable of inducing morphological and preneoplastic transformation. In carefully designed animal experiments, chrysotile produces lung cancer and mesothelioma as effectively as do the amphiboles tested. Human population studies do not refute these experimental results. Chrysotile asbestos is carcinogenic to humans, especially for the induction of lung cancer and mesothelioma in exposed populations. For cancers of other sites, with the exception of laryngeal and possibly gastrointestinal cancer, the evidence for association with exposure to all forms of asbestos, including chrysotile, is not yet adequate for evaluation.}, } @article {pmid1809159, year = {1991}, author = {Lilienfeld, DE}, title = {Asbestos-associated pleural mesothelioma in school teachers: a discussion of four cases.}, journal = {Annals of the New York Academy of Sciences}, volume = {643}, number = {}, pages = {454-458}, doi = {10.1111/j.1749-6632.1991.tb24494.x}, pmid = {1809159}, issn = {0077-8923}, support = {K08-ES00161/ES/NIEHS NIH HHS/United States ; P01-ES00928/ES/NIEHS NIH HHS/United States ; }, mesh = {Adult ; Air Pollution, Indoor/*adverse effects ; Asbestos/*adverse effects/isolation & purification ; Female ; Humans ; Male ; Mesothelioma/*etiology/physiopathology ; Middle Aged ; Pleural Neoplasms/*etiology/physiopathology ; *Schools ; Teaching ; }, abstract = {The causal relationship between malignant mesothelioma and exposure to asbestos is well established. In part as a result of that association, much public attention has focused on asbestos abatement in buildings, such as public schools, in which that asbestos was used as a construction material. The present communication is a report of four cases of malignant mesothelioma in school teachers whose only apparent exposure to asbestos was in the schools in which they taught. The concerns raised by this report are also discussed.}, } @article {pmid1809157, year = {1991}, author = {Viallat, JR and Boutin, C and Steinbauer, J and Gaudichet, A and Dufour, G}, title = {Pleural effects of environmental asbestos pollution in Corsica.}, journal = {Annals of the New York Academy of Sciences}, volume = {643}, number = {}, pages = {438-443}, doi = {10.1111/j.1749-6632.1991.tb24491.x}, pmid = {1809157}, issn = {0077-8923}, mesh = {Aged ; Aged, 80 and over ; Air Pollutants/*adverse effects ; Asbestos/*adverse effects/isolation & purification ; Female ; France ; Humans ; Male ; Mesothelioma/*epidemiology/etiology/pathology ; Middle Aged ; Occupational Diseases/*epidemiology/etiology ; Pleural Diseases/diagnostic imaging/*epidemiology/etiology ; Pleural Neoplasms/*epidemiology/etiology/pathology ; Radiography ; }, } @article {pmid1809153, year = {1991}, author = {Woitowitz, HJ}, title = {Aspects of asbestos exposure in place in the Federal Republic of Germany.}, journal = {Annals of the New York Academy of Sciences}, volume = {643}, number = {}, pages = {407-411}, doi = {10.1111/j.1749-6632.1991.tb24486.x}, pmid = {1809153}, issn = {0077-8923}, mesh = {Asbestos/*adverse effects/isolation & purification ; Body Burden ; Female ; Germany, West ; Humans ; Lung Neoplasms/*epidemiology/etiology/pathology ; Male ; Mesothelioma/*epidemiology/etiology/pathology ; Occupational Diseases/*epidemiology/etiology ; }, } @article {pmid1809152, year = {1991}, author = {Rüttner, JR}, title = {Mesothelioma in Swiss railroad workers.}, journal = {Annals of the New York Academy of Sciences}, volume = {643}, number = {}, pages = {404-406}, doi = {10.1111/j.1749-6632.1991.tb24485.x}, pmid = {1809152}, issn = {0077-8923}, mesh = {Asbestos/*adverse effects ; Dust ; Female ; Humans ; Male ; Mesothelioma/*epidemiology/etiology ; Occupational Diseases/*epidemiology/etiology ; Peritoneal Neoplasms/*epidemiology/etiology ; Pleural Neoplasms/*epidemiology/etiology ; *Railroads ; Switzerland ; }, } @article {pmid1809149, year = {1991}, author = {Mehlman, MA}, title = {Dangerous and cancer-causing properties of products and chemicals in the oil-refining and petrochemical industries. Part IX: Asbestos exposure and analysis of exposures.}, journal = {Annals of the New York Academy of Sciences}, volume = {643}, number = {}, pages = {368-389}, doi = {10.1111/j.1749-6632.1991.tb24482.x}, pmid = {1809149}, issn = {0077-8923}, mesh = {Asbestos/*adverse effects ; Asbestosis/epidemiology/*etiology ; Humans ; Lung Neoplasms/epidemiology/etiology ; Mesothelioma/epidemiology/etiology ; Occupational Diseases/epidemiology/*etiology ; *Petroleum ; United States ; }, } @article {pmid1809148, year = {1991}, author = {Maltoni, C and Pinto, C and Mobiglia, A}, title = {Mesotheliomas due to asbestos used in railroads in Italy.}, journal = {Annals of the New York Academy of Sciences}, volume = {643}, number = {}, pages = {347-367}, doi = {10.1111/j.1749-6632.1991.tb24481.x}, pmid = {1809148}, issn = {0077-8923}, mesh = {Epidemiologic Methods ; Humans ; Italy ; Lung Neoplasms/epidemiology/*etiology/mortality ; Mesothelioma/epidemiology/*etiology/mortality ; Occupational Diseases/epidemiology/*etiology/mortality ; *Railroads ; Risk Factors ; }, abstract = {The available knowledge of the oncogenic risks of asbestos, the presentation of some data on the uses of asbestos in railroads, with particular regard to the Italian State Railroads (Ferrovie dello Stato = FS), and the identification of groups at risk because of exposure to asbestos used in railroads are briefly reviewed. The available data in the literature on the pathologic effects of such exposure, and in particular on the onset of mesotheliomas among machinists and other railroad workers, are also summarized. Eighty-three cases, in various Italian regions, of mesothelioma (78 pleural, 4, peritoneal, and 1 pericardial) are reported that are related to the exposure to asbestos used in railroads. Twenty-six of these cases (among which 25 were reported in the Emilia-Romagna region) were submitted to a detailed study at the Bologna Institute of Oncology. Forty-nine cases of mesothelioma occurred among FS workers, in particular machinists; 29 cases occurred among machinists of rolling-stock workshops not belonging to the FS; 3 cases occurred among travelling workers of rolling-stock not belonging to the FS; 2 cases were found in members of the family (a daughter and a wife) of FS workers. This series of cases, together with similar data from the literature, proves the existence and gravity of an actual health risk due to asbestos used in the railroads. On the basis of the available data, the following steps are considered necessary: the adoption of preventive measures, the performance of medical oncological surveillance, the promotion of systematic epidemiologic investigations, and, finally, the placement of greater emphasis on basic research, aimed at generating information on the biological events taking place during the incubation period of the tumors. This information, hopefully, could be used to reduce the biological effect of exposure, and therefore for controlling the neoplastic process before onset of the disease in those who, having been exposed, although healthy, are potentially at risk.}, } @article {pmid1809147, year = {1991}, author = {Mancuso, TF}, title = {Mesotheliomas among railroad workers in the United States.}, journal = {Annals of the New York Academy of Sciences}, volume = {643}, number = {}, pages = {333-346}, doi = {10.1111/j.1749-6632.1991.tb24480.x}, pmid = {1809147}, issn = {0077-8923}, mesh = {Adult ; Asbestos/adverse effects ; Cause of Death ; Cohort Studies ; Humans ; Lung Neoplasms/*epidemiology/etiology/mortality ; Male ; Mesothelioma/*epidemiology/etiology/mortality ; Occupational Diseases/*epidemiology/etiology/mortality ; *Railroads ; United States ; }, } @article {pmid1809146, year = {1991}, author = {Greenberg, M}, title = {Cancer mortality in merchant seamen.}, journal = {Annals of the New York Academy of Sciences}, volume = {643}, number = {}, pages = {321-332}, doi = {10.1111/j.1749-6632.1991.tb24479.x}, pmid = {1809146}, issn = {0077-8923}, mesh = {Adolescent ; Adult ; Aged ; Asbestos/adverse effects ; Cause of Death ; Female ; Humans ; Lung Neoplasms/etiology/mortality ; Male ; Mesothelioma/etiology/mortality ; Middle Aged ; Naval Medicine ; Neoplasms/epidemiology/etiology/*mortality ; Registries ; Risk Factors ; *Ships ; United Kingdom ; }, abstract = {Cancer mortality excess has been reported repeatedly over the past hundred years to occur in merchant seamen. More recently lung cancer has been found to account for some of this excess and the question of the contribution made by cigarette smoking raised. In the one study where there was some information on smoking habit, it did not appear that cigarettes would have accounted for all the excess cancer observed. In other mortality studies, where excess cancer mortality was observed, the other cigarette-linked causes of death were not prominent. In a preliminary mortality analysis of a small population of merchant seamen, two cases of malignant mesothelioma have so far been identified, and in a national mesothelioma register 28 cases have been reported in seamen: both instances constitute abnormal occurrences. The presence of substantial amounts of asbestos-containing materials in naval construction which are continuously subjected to vibration and intermittently disturbed during servicing, and the detection of radiological stigmata consistent with asbestos exposure, add plausibility to the hypothesis that occupational asbestos exposure contributes to the apparent excess cancer mortality in merchant seamen. Methodologic deficiencies in epidemiologic studies reported to date make for uncertainty. Properly designed studies will be needed to quantify disease excess and to identify potentially causal associations. Even in the absence of such data it would be prudent to contain the asbestos currently installed and to promote smoking cessation programs.}, } @article {pmid1809141, year = {1991}, author = {Landrigan, PJ}, title = {A population of children at risk of exposure to asbestos in place.}, journal = {Annals of the New York Academy of Sciences}, volume = {643}, number = {}, pages = {283-286}, doi = {10.1111/j.1749-6632.1991.tb24473.x}, pmid = {1809141}, issn = {0077-8923}, mesh = {Air Pollution, Indoor/*adverse effects ; Asbestos/*adverse effects ; Child ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Risk Factors ; *Schools ; }, } @article {pmid1809139, year = {1991}, author = {Kohyama, N and Suzuki, Y}, title = {Analysis of asbestos fibers in lung parenchyma, pleural plaques, and mesothelioma tissues of North American insulation workers.}, journal = {Annals of the New York Academy of Sciences}, volume = {643}, number = {}, pages = {27-52}, doi = {10.1111/j.1749-6632.1991.tb24442.x}, pmid = {1809139}, issn = {0077-8923}, support = {ES00928/ES/NIEHS NIH HHS/United States ; }, mesh = {Adult ; Asbestos/*isolation & purification ; Asbestosis/etiology/*pathology ; Body Burden ; Construction Materials ; Humans ; Lung Neoplasms/etiology/*pathology ; Male ; Mesothelioma/etiology/*pathology ; North America ; Occupational Diseases/etiology/*pathology ; Pleura/*pathology ; Time Factors ; }, abstract = {Asbestos fibers and ferruginous bodies (FBs) in lung parenchyma, lung cancer tissues, pleural plaques, and pleural and peritoneal mesothelioma tissues from 13 North American insulation workers were analyzed and quantified using an analytical transmission electron microscope and a polarized microscope. Diseases from which these workers suffered included asbestosis, lung cancer, and mesothelioma. They had been occupationally exposed to materials containing chrysotile and amosite; their pathological diagnoses, occupational and cigarette smoking histories, and clinical summaries have been reported. Large numbers of FBs were found in the lungs and small numbers found in extrapulmonary sites. Most of the FBs had cores of amosite fibers. In all instances, lung parenchyma and lung cancer tissues showed chrysotile and amosite fibers in high concentrations (63.1 x 10(6) and 150.2 x 10(6) fibers/g dry tissue as mean values, respectively). Crocidolite fibers were seen in seven of the 13 cases, but in much smaller numbers. Other amphiboles were rarely found. In pleural plaques and in pleural and peritoneal mesothelioma tissues, amosite fibers were markedly fewer in number, whereas chrysotile fibers were seen in similar numbers as in the lungs. No significant differences in the size distribution of asbestos fibers were seen in the different sites. However, the mean widths of chrysotile fibers were thinner than those of amosite fibers. These results strongly suggest that translocation of inhaled asbestos fibers from the lung to other tissues, such as the pleura and the peritoneum, occurs frequently, and that chrysotile may be more actively translocated from the lung, compared to amosite or amphibole asbestos. The likelihood of translocation seems to be strongly related to the thinness of the fibers. Translocated chrysotile fibers may play an important role in the induction of either malignant mesothelioma and/or hyaline plaques, since the asbestos fibers detected in both these sites were mainly chrysotile.}, } @article {pmid1809138, year = {1991}, author = {Jaurand, MC}, title = {Observations on the carcinogenicity of asbestos fibers.}, journal = {Annals of the New York Academy of Sciences}, volume = {643}, number = {}, pages = {258-270}, doi = {10.1111/j.1749-6632.1991.tb24470.x}, pmid = {1809138}, issn = {0077-8923}, mesh = {Animals ; Asbestos/*toxicity ; *Carcinogens ; Lung Neoplasms/*etiology/metabolism ; Magnesium/metabolism ; Mesothelioma/*etiology/metabolism ; Particle Size ; }, abstract = {This paper summarizes animal experiments and in vitro data carried out to study the oncogenic effects of asbestos fibers on mesothelial cells. An interpretation of the results is made in light of current statements on the carcinogenicity of asbestos fibers. Experimental results appear to show that the carcinogenicity of mineral fibers is a complex, multiparametric phenomenon. Chromosomal mutations and possibly oxygen derivatives are involved in the genesis of the fiber-induced neoplastic process and may be the result of the intrinsic fiber properties, size, and physicochemistry. The role of fiber solubility is discussed; it is suggested that additional experiments are necessary for a better understanding of the importance of solubility in the concept of biopersistence.}, } @article {pmid1809134, year = {1991}, author = {Suzuki, Y}, title = {Comparability of mesothelioma in humans and in experimental animal studies.}, journal = {Annals of the New York Academy of Sciences}, volume = {643}, number = {}, pages = {219-222}, doi = {10.1111/j.1749-6632.1991.tb24465.x}, pmid = {1809134}, issn = {0077-8923}, mesh = {Animals ; Asbestos/*adverse effects ; Body Burden ; Humans ; Lung Neoplasms/*etiology/pathology ; Mesothelioma/*etiology/pathology ; }, } @article {pmid1809133, year = {1991}, author = {Pott, F}, title = {Neoplastic findings in experimental asbestos studies and conclusions for fiber carcinogenesis in humans.}, journal = {Annals of the New York Academy of Sciences}, volume = {643}, number = {}, pages = {205-218}, doi = {10.1111/j.1749-6632.1991.tb24464.x}, pmid = {1809133}, issn = {0077-8923}, mesh = {Administration, Inhalation ; Animals ; Asbestos/*toxicity ; Body Burden ; *Carcinogens ; Humans ; Injections, Intraperitoneal ; Lung Neoplasms/*etiology/pathology ; Mesothelioma/*etiology/pathology ; }, } @article {pmid1809132, year = {1991}, author = {Mark, EJ and Yokoi, T}, title = {Absence of evidence for a significant background incidence of diffuse malignant mesothelioma apart from asbestos exposure.}, journal = {Annals of the New York Academy of Sciences}, volume = {643}, number = {}, pages = {196-204}, doi = {10.1111/j.1749-6632.1991.tb24463.x}, pmid = {1809132}, issn = {0077-8923}, mesh = {Asbestos/adverse effects ; Humans ; Lung Neoplasms/*epidemiology/etiology/pathology ; Mesothelioma/*epidemiology/etiology/pathology ; Retrospective Studies ; }, abstract = {The incidence of diffuse malignant mesothelioma is rising. Physicians can diagnose a disease only when they know that it exists, so one explanation for the rise in incidence is more widespread appreciation of the clinical and pathological features of the disease. Modern pathology has ascribed specific requirements for the diagnosis of diffuse malignant mesothelioma. A priori one cannot assume that these requirements have increased the likelihood of the diagnosis because the requirements also can serve to exclude the diagnosis depending on the findings. Most cases of diffuse malignant mesothelioma are suspected by macroscopic and routine microscopic techniques that have been available since the last part of the nineteenth century. Although single reported instances of some pulmonary diseases have survived from the nineteenth century, pathologists did not identify enough cases to convincingly establish the existence of diffuse malignant mesothelioma of the pleura as an entity until the 1930s or 1940s. One must conclude that the background level of diffuse malignant mesothelioma in Europe and in the United States prior to 1930 was extremely low. No case was detected at the Massachusetts General Hospital until 1946.}, } @article {pmid1809131, year = {1991}, author = {Sluis-Cremer, GK}, title = {Asbestos disease at low exposures after long residence times.}, journal = {Annals of the New York Academy of Sciences}, volume = {643}, number = {}, pages = {182-193}, doi = {10.1111/j.1749-6632.1991.tb24461.x}, pmid = {1809131}, issn = {0077-8923}, mesh = {Adult ; Asbestosis/diagnostic imaging/epidemiology/*etiology ; Carcinoma, Bronchogenic/etiology/mortality ; Epidemiologic Methods ; Follow-Up Studies ; Humans ; Lung Neoplasms/etiology/mortality ; Male ; Mesothelioma/etiology/mortality ; *Mining ; Occupational Diseases/epidemiology/*etiology ; Radiography ; Smoking/adverse effects ; South Africa ; Time Factors ; }, } @article {pmid1808384, year = {1991}, author = {Kishimoto, T}, title = {[A case of benign localized mesothelioma with occupational history of asbestos exposure].}, journal = {Nihon Kyobu Shikkan Gakkai zasshi}, volume = {29}, number = {12}, pages = {1603-1607}, pmid = {1808384}, issn = {0301-1542}, mesh = {Aged ; Asbestos/*adverse effects ; Diagnosis, Differential ; Humans ; Lung Neoplasms/*etiology/pathology ; Male ; Mesothelioma/*etiology/pathology ; *Occupational Exposure ; }, abstract = {A case of localized mesothelioma with a history of asbestos exposure is reported. A significant number of ferruginous bodies were detected in the lung of autopsy. The tumor mainly consisted of which did not show mitosis. The tumor stained weakly with cytokeratin and vimentin. Thus, this tumor was very difficult to differentiate from malignant mesothelioma. Clinical symptoms such as pulmonary osteoarthropathy, hypoglycemia, and very slow growth are important characteristics in the diagnosis of localized benign mesothelioma.}, } @article {pmid1801838, year = {1991}, author = {Friedrichs, KH and Teschler, H and Wick, G and Konietzko, N and Costabel, U}, title = {[Asbestos content in bronchoalveolar lavage fluid].}, journal = {Zentralblatt fur Hygiene und Umweltmedizin = International journal of hygiene and environmental medicine}, volume = {192}, number = {4}, pages = {336-343}, pmid = {1801838}, issn = {0934-8859}, mesh = {Asbestos/*analysis ; Bronchoalveolar Lavage Fluid/*chemistry ; Humans ; Microscopy, Electron ; *Occupational Exposure ; Regression Analysis ; }, abstract = {The concentration and size distribution of bronchoalveolar lavage (BAL) asbestos fibers (AF) longer than 2 microns was determined by analytical transmission electron microscopy (TEM). The concentration of asbestos bodies (AB) was measured by TEM and light microscopy (LM). The study group consisted of 110 patients. 27 patients had no occupational asbestos exposure, 44 patients had occupational exposure to asbestos but no asbestos related disease and 39 patients had asbestos related diseases, either asbestosis (n = 34) or malignant mesothelioma of the pleura (n = 5) following long time asbestos exposure at the working place. Occupational asbestos exposure was reflected by increased asbestos fiber concentration in the BAL samples. Mean fiber concentration and size was different between the groups, but the scatter was large.}, } @article {pmid1788534, year = {1991}, author = {Tuomi, T and Huuskonen, MS and Virtamo, M and Tossavainen, A and Tammilehto, L and Mattson, K and Lahdensuo, A and Mattila, J and Karhunen, P and Liippo, K}, title = {Relative risk of mesothelioma associated with different levels of exposure to asbestos.}, journal = {Scandinavian journal of work, environment & health}, volume = {17}, number = {6}, pages = {404-408}, doi = {10.5271/sjweh.1686}, pmid = {1788534}, issn = {0355-3140}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Asbestosis/*pathology ; Cell Transformation, Neoplastic/pathology ; Humans ; Lung/pathology ; Lung Diseases/pathology ; Lung Neoplasms/*pathology ; Male ; Mesothelioma/*pathology ; Microscopy, Electron ; Middle Aged ; *Occupational Exposure ; Risk Factors ; Sarcoidosis/pathology ; Smoking/adverse effects/pathology ; }, abstract = {The relative risk of mesothelioma associated with different levels of exposure to asbestos was evaluated. The exposure was assessed from work histories of 51 mesothelioma cases and 51 sarcoidosis referents. The lung fiber concentration of the mesothelioma patients was compared with that of two reference groups (13 random autopsy cases and 43 male lung cancer patients). When the categories definite and probable were used as an estimated probability of occupational exposure, an odds ratio of 17.7 [90% confidence interval (90% CI) 3.4-253] and 3.0 (90% CI 0.9-10.6), respectively, was obtained. A lung fiber concentration of greater than 1 million fibers/g of dry tissue as an indicator of accumulated exposure gave an odds ratio of 14.4 (90% CI 2.5-178) for the men in comparison with the autopsy cases and 3.1 (90% CI, 1.3-7.5) in comparison with the lung cancer patients. Elevated risk of mesothelioma was shown to be associated with a lung fiber concentration of greater than 1 million fibers/g of dry tissue.}, } @article {pmid1663385, year = {1991}, author = {Berry, G}, title = {Prediction of mesothelioma, lung cancer, and asbestosis in former Wittenoom asbestos workers.}, journal = {British journal of industrial medicine}, volume = {48}, number = {12}, pages = {793-802}, pmid = {1663385}, issn = {0007-1072}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Asbestos, Crocidolite ; Asbestosis/*mortality ; Cause of Death ; Female ; Forecasting/methods ; Humans ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; Middle Aged ; *Mining ; Time Factors ; Western Australia/epidemiology ; }, abstract = {Projections have been made of the number of mesotheliomas, lung cancers, and cases of asbestosis that might occur over the period 1987 to 2020 in former workers at the Wittenoom crocidolite asbestos mine in Western Australia. Predictions were based on the observed mortality to the end of 1986 and modelling of the mesothelioma rate. Elimination of crocidolite from the lungs was included in the model. Between the years 1987 and 2020 it is predicted that between 250 and 680 deaths will occur due to mesothelioma. This wide range is due to uncertainty on the functional form of the relation between mesothelioma rate and time, and insufficient data to estimate the elimination rate of crocidolite from the lungs. The most likely range is the lower half of this total range--that is, between 250 and 500. It is predicted that between 340 and 465 deaths will occur due to lung cancer. About 45% of these deaths would be attributable to exposure to asbestos. It is estimated that currently there are up to 200 cases of undiagnosed asbestosis. Of these about 50 will die of lung cancer or mesothelioma and are therefore also included in the figures above. Up to 60 former workers may develop the first signs of asbestosis in the future but any such cases are likely to progress to more serious disease at a much slower rate than the cases that have already been identified.}, } @article {pmid1950982, year = {1991}, author = {Demers, R}, title = {Overview of radon, lead and asbestos exposure.}, journal = {American family physician}, volume = {44}, number = {5 Suppl}, pages = {51S-52S, 55S-61S}, pmid = {1950982}, issn = {0002-838X}, mesh = {Adult ; Asbestos/*adverse effects ; Child ; Environmental Exposure/*adverse effects ; Humans ; Lead/*adverse effects ; Lung Diseases/etiology ; Occupational Diseases/etiology ; Radon/*adverse effects ; }, abstract = {Reducing the incidence of diseases caused by exposure to radon, lead and asbestos is a major public health challenge. Radon gas, which usually enters a home through the foundation, can cause lung cancer. Exposure to lead through paint, auto emissions and other sources can cause neurologic deficits, as well as anemia, abnormal vitamin D metabolism, nephropathy, hypertension and reproductive abnormalities. Asbestos, which is used in a vast number of products, is primarily associated with parenchymal asbestosis, pleural fibrosis, mesothelioma and lung cancer. The family physician can play a pivotal role in providing information about hazardous exposure, sources of exposure, epidemiology and disease prevention.}, } @article {pmid1766579, year = {1991}, author = {Mirabella, F}, title = {[Malignant mesothelioma of the tunica vaginalis of the testis. Here again asbestos?].}, journal = {Minerva medica}, volume = {82}, number = {11}, pages = {765-770}, pmid = {1766579}, issn = {0026-4806}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Humans ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Testicular Neoplasms/*epidemiology/etiology ; }, abstract = {Malignant mesothelioma of the tunica vaginalis testis is a fairly rare disease, but it seems to have become more common in the last few years, according to epidemiological data. At least 45 cases have been reported in medical literature, 29 of which originating from Anglo-Saxon countries. Asbestos is the aetiological factor that is becoming more apparent also in this location of mesothelioma. From Fligiel's first case to the latest published by Tyagi, there have been 11 established cases of exposure to asbestos, which is equivalent of at least 31.5% among those affected by the illness. In many cases, furthermore, this noxious substance has not even been investigated.}, } @article {pmid1659443, year = {1991}, author = {Gibbs, AR and Stephens, M and Griffiths, DM and Blight, BJ and Pooley, FD}, title = {Fibre distribution in the lungs and pleura of subjects with asbestos related diffuse pleural fibrosis.}, journal = {British journal of industrial medicine}, volume = {48}, number = {11}, pages = {762-770}, pmid = {1659443}, issn = {0007-1072}, mesh = {Aged ; Aged, 80 and over ; Asbestos/adverse effects/*analysis ; Asbestos, Amosite ; Asbestos, Crocidolite ; Asbestos, Serpentine ; Fibrosis ; Humans ; Lung/*chemistry ; Male ; Middle Aged ; Occupational Diseases/*etiology ; Pleura/*chemistry/pathology ; }, abstract = {The lungs from 13 cases of diffuse pleural fibrosis associated with a history of exposure to asbestos were examined. Samples were taken from the visceral pleura and central and subpleural zones of the lungs for histopathological and mineralogical studies. The fibre type, size, and number were estimated for each of these regions by transmission electron microscopy and energy dispersive x ray analysis. Amphibole fibre counts were raised when compared with a non-occupationally exposed group and matched those seen in cases of pleural plaques, mild asbestosis, and mesothelioma. A wide case to case variation of distribution was seen. No significant difference was apparent between central and subpleural zones, whereas low asbestos counts were found in the pleura; these were mainly short chrysotile fibres. Within the lungs more (45%) of the longer (greater than 4 microns) and thinner (less than 0.25 micron) amphibole fibres were retained in keeping with other studies implicating such fibre profiles in the pathogenesis of asbestos related disease.}, } @article {pmid1681294, year = {1991}, author = {Browne, K}, title = {Environmental asbestos.}, journal = {Lancet (London, England)}, volume = {338}, number = {8772}, pages = {949}, doi = {10.1016/0140-6736(91)91818-f}, pmid = {1681294}, issn = {0140-6736}, mesh = {Asbestos/*adverse effects ; *Environmental Exposure ; Humans ; Italy ; Mesothelioma/*etiology ; *Occupational Exposure ; Pleural Neoplasms/*etiology ; }, } @article {pmid1931726, year = {1991}, author = {Becker, N and Chang-Claude, J and Frentzel-Beyme, R}, title = {Risk of cancer for arc welders in the Federal Republic of Germany: results of a second follow up (1983-8).}, journal = {British journal of industrial medicine}, volume = {48}, number = {10}, pages = {675-683}, pmid = {1931726}, issn = {0007-1072}, mesh = {Follow-Up Studies ; Germany, West ; Humans ; Male ; Neoplasms/*etiology/mortality ; Occupational Diseases/*etiology/mortality ; Occupational Exposure ; Risk Factors ; Smoking/adverse effects ; Time Factors ; *Welding ; }, abstract = {An extended follow up of 1221 chromium and nickel exposed welders in the Federal Republic of Germany confirmed an increased relative risk of 1.6 for all cancers compared with an internal reference group of 1694 turners. In an external comparison an excess of deaths from malignant tumours compared with that expected from the national mortality rates was found (standardised mortality ratio (SMR) = 109), which was clearly related to both time since first exposure and duration of exposure. Mortality from lung cancer was increased among welders (SMR = 113) but also among turners (SMR = 108). The difference remained when the subgroups were compared according to smoking information. A large excess of mesothelioma as a cause of death could be attributed to exposure to asbestos. The significantly increased SMR seen for urogenital tumours and "other or unspecified tumours" showed, however, an inverse relation with time since first exposure. This and other inconsistencies in the analysis by type of welding do not permit conclusive statements. Thus a further extension of follow up seems warranted.}, } @article {pmid1913660, year = {1991}, author = {Cote, RJ and Jhanwar, SC and Novick, S and Pellicer, A}, title = {Genetic alterations of the p53 gene are a feature of malignant mesotheliomas.}, journal = {Cancer research}, volume = {51}, number = {19}, pages = {5410-5416}, pmid = {1913660}, issn = {0008-5472}, support = {CA-50434/CA/NCI NIH HHS/United States ; }, mesh = {Blotting, Northern ; Blotting, Southern ; Cell Line ; Chromosome Aberrations ; Chromosomes, Human, Pair 17 ; DNA/analysis ; Gene Amplification ; Genes, p53/*genetics ; Humans ; Karyotyping ; Mesothelioma/*genetics ; *Mutation ; RNA, Messenger/biosynthesis ; Transcription, Genetic ; }, abstract = {A putative tumor suppressor gene, p53, has been shown to be altered in a variety of human tumor types. The primary mechanism of p53 inactivation is believed to be mutation of one allele followed by loss of the second allele. Malignant mesothelioma is a tumor that has been highly associated with exposure to asbestos fibers, which are known to cause chromosomal abnormalities in mesothelial cells. We have examined four mesothelioma cell lines for genetic abnormalities in p53. Cytogenetic analysis revealed that two of the four tumors had abnormalities (numerical and/or structural) of chromosome 17 (the locus of the p53 gene). Restriction fragment length polymorphism analysis using a chromosome 17p-specific probe (pYNZ22) revealed that two tumors had loss of heterozygosity in the region of 17p13. The relative level of p53 mRNA expression was examined by Northern analysis, with one tumor showing negligible expression of p53 mRNA. The complementary DNA of p53 was generated from the three tumors showing detectable mRNA expression, and the region between codons 70 and 319 was amplified by the polymerase chain reaction and sequenced. DNA single-base substitutions were detected in two of the tumor cell lines, each resulting in amino acid substitutions. One tumor had an arginine to histidine substitution at position 175, and one tumor had a glycine to aspartic acid substitution at position 245. The observed mutations took place in regions of high cross-species sequence homology, indicating that these regions may be functionally important. The correlation of chromosomal loss in 17p on the cytogenetic and molecular level along with p53 mRNA expression and DNA sequence data indicate that genetic alterations in p53 could be a feature of malignant mesotheliomas and may reveal an important role of asbestos fibers in tumor suppressor gene inactivation.}, } @article {pmid1842686, year = {1991}, author = {Pluygers, E and Baldewyns, P and Minette, P and Beauduin, M and Gourdin, P and Robinet, P}, title = {Biomarker assessments in asbestos-exposed workers as indicators for selective prevention of mesothelioma or bronchogenic carcinoma: rationale and practical implementations.}, journal = {European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP)}, volume = {1}, number = {1}, pages = {57-68}, doi = {10.1097/00008469-199110000-00011}, pmid = {1842686}, issn = {0959-8278}, mesh = {Antigens, Neoplasm/blood ; Antigens, Tumor-Associated, Carbohydrate/blood ; Asbestos/*adverse effects ; Asbestosis/blood ; Biomarkers, Tumor/*blood ; Carcinoembryonic Antigen/blood ; Carcinoma, Bronchogenic/*blood/*prevention & control ; Ferritins/blood ; Humans ; Hyaluronic Acid/blood ; Lung Neoplasms/*blood/*prevention & control ; Mesothelioma/*blood/*prevention & control ; Occupational Diseases/*blood/*prevention & control ; *Occupational Exposure ; Peptides/blood ; Phosphopyruvate Hydratase/blood ; Tissue Polypeptide Antigen ; }, abstract = {Asbestos-associated malignancies are one of the major industrial hazards of recent decades and will continue to be so until beyond the end of the century. It has been estimated that, in the United States alone, there will be 131,200 cancer deaths as a result of asbestos exposure. At present the early lesions are detected radiologically, by which time intervention is no longer effective. The aim of this study was to test the value of a battery of serum biomarkers in the early detection of malignancy and in distinguishing between the early stages of mesothelioma and bronchogenic carcinoma. Many of the biomarkers had no discriminating value but on the basis of four such markers (namely TPA, CEA, HA and ferritin) it has been possible to distinguish between the late stages of the two malignancies and asbestosis. The results are discussed in terms of their possible application to the detection of early pre-malignant lesions in a screened population of asbestos-exposed persons, with the aim of attempting to prevent cancer death in such early detected cases.}, } @article {pmid1743578, year = {1991}, author = {Grossgarten, K and Woitowitz, HJ}, title = {[Fatal peritoneal mesothelioma disease in women caused by asbestos exposure at the work place].}, journal = {Der Gynakologe}, volume = {24}, number = {5}, pages = {261-264}, pmid = {1743578}, issn = {0017-5994}, mesh = {Asbestos/*adverse effects ; Diagnosis, Differential ; Female ; Humans ; Mesothelioma/diagnosis/etiology/*mortality ; *Occupational Exposure ; Occupational Medicine ; Ovarian Neoplasms/diagnosis/pathology ; Peritoneal Neoplasms/etiology/*mortality/secondary ; }, } @article {pmid1742204, year = {1991}, author = {Davis, JM and Jones, AD and Miller, BG}, title = {Experimental studies in rats on the effects of asbestos inhalation coupled with the inhalation of titanium dioxide or quartz.}, journal = {International journal of experimental pathology}, volume = {72}, number = {5}, pages = {501-525}, pmid = {1742204}, issn = {0959-9673}, mesh = {Animals ; Asbestos/*toxicity ; Asbestosis/pathology ; Dust ; Environmental Exposure ; Lung/pathology ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Pulmonary Fibrosis/*etiology/pathology ; Quartz/*toxicity ; Rats ; Time Factors ; Titanium/*toxicity ; }, abstract = {Rats were exposed for 1 year, with a 2-year follow-up, to dust clouds consisting of a mixture of amosite or chrysotile asbestos with either titanium dioxide or quartz. The addition of titanium dioxide to asbestos did not increase levels of pulmonary fibrosis above the amounts produced by chrysotile or amosite alone. Quartz, however, greatly increased fibrosis above that produced by the asbestos types alone. Both particulate dusts caused an increase in the numbers of pulmonary tumours and mesotheliomas compared to asbestos alone but while tumours in animals treated with asbestos and quartz tended to occur earlier than tumours with asbestos alone, in animals treated with dusts containing titanium dioxide, tumour production occurred later than with asbestos alone. In animals treated with mixtures of asbestos and quartz, there was evidence of increased transport of fibres across the visceral pleural surface and this may be associated with the finding of a higher proportion of pleural mesotheliomas than previously reported in experimental inhalation studies from any laboratory using the main asbestos varieties. The presence of particulate dusts made little difference to the amounts of amosite fibre retained in the lung tissue but, with chrysotile, titanium dioxide appeared to increase retention while quartz reduced it.}, } @article {pmid1749207, year = {1991}, author = {Turk, J and Kenda, M and Kranjec, I}, title = {Primary malignant pericardial mesothelioma.}, journal = {Klinische Wochenschrift}, volume = {69}, number = {14}, pages = {674-678}, pmid = {1749207}, issn = {0023-2173}, mesh = {Adult ; Aged ; Cardiac Tamponade/diagnosis/pathology ; Echocardiography ; *Electrocardiography ; Humans ; Male ; Mediastinal Neoplasms/*diagnosis/pathology ; Mesothelioma/*diagnosis/pathology ; Myocardium/pathology ; Pericardial Effusion/diagnosis/pathology ; Pericarditis/diagnosis/pathology ; *Pericardium/pathology ; }, abstract = {Malignant primary tumors of the pericardium are rare. The authors present two male patients, aged 44 and 67 years, not exposed to asbestos, who died from pericardial mesothelioma. Repeated evacuation of fluid from the pericardium due to cardiac tamponade failed to reveal the cause of pericarditis. In one case, the diagnosis was made on surgical exploration, and in the other, at autopsy. A significant difference between benign and malignant pericardial effusion was observed. In cases of pericardial mesothelioma, symptoms of epicardial involvement cannot be attributed solely to the hindered inflow and cardiac tamponade, but also to congestive heart failure due to myocardial infiltration. In one patient, temporary improvement was achieved, first by pronisone therapy and then by radiotherapy.}, } @article {pmid1679496, year = {1991}, author = {Reid, AS and Causton, BE and Jones, JS and Ellis, IO}, title = {Malignant mesothelioma after exposure to asbestos in dental practice.}, journal = {Lancet (London, England)}, volume = {338}, number = {8768}, pages = {696}, doi = {10.1016/0140-6736(91)91273-w}, pmid = {1679496}, issn = {0140-6736}, mesh = {Asbestos/*adverse effects ; Asbestos, Crocidolite ; Dental Casting Technique/*adverse effects ; Humans ; Lung Neoplasms/*etiology ; Male ; Mesothelioma/*etiology ; Middle Aged ; Occupational Diseases/*etiology ; Periodontal Dressings/adverse effects ; }, } @article {pmid1836508, year = {1991}, author = {Kishimoto, T}, title = {[The distribution of various type of oncogenes products in the tumor tissue of malignant mesothelioma].}, journal = {Nihon Kyobu Shikkan Gakkai zasshi}, volume = {29}, number = {9}, pages = {1168-1173}, pmid = {1836508}, issn = {0301-1542}, mesh = {Aged ; Asbestos/*adverse effects ; Humans ; Immunoenzyme Techniques ; Lung Neoplasms/*genetics/metabolism ; Male ; Mesothelioma/*genetics/metabolism ; Middle Aged ; Oncogene Proteins/*metabolism ; *Proto-Oncogenes ; }, abstract = {The distribution of various oncogenes in the tumor tissues of 8 cases of malignant mesothelioma related to asbestos exposure was evaluated by monoclonal antibodies against oncogenes. There was no staining for K-ras, H-ras and erb-B in all cases and C-abl slightly stained in only one case of a biphasic type of tumor. On the other hand, C-myc positively stained in epithelioid type and the epitheloidal portion of the biphasic type of tumors. C-neu, C-fos and N-myc positively stained in almost all cases. Of these 9 oncogenes, C-neu was most frequently stained in all cases. These results suggest that C-myc, N-myc, C-neu and C-fos oncogenes may have some role in the appearance of malignant mesothelioma related to asbestos exposure.}, } @article {pmid1782687, year = {1991}, author = {Tan, XM}, title = {[Pathologic study of pleural and peritoneal mesotheliomas of rats induced by asbestos].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {20}, number = {3}, pages = {187-189}, pmid = {1782687}, issn = {0529-5807}, mesh = {Adenocarcinoma/pathology ; Animals ; *Asbestos ; Diagnosis, Differential ; Humans ; Immunohistochemistry ; Mesothelioma/etiology/*pathology ; Peritoneal Neoplasms/etiology/*pathology ; Pleural Neoplasms/etiology/*pathology ; Rats ; }, abstract = {Forty-six cases of mesotheliomas of rats induced by asbestos, 2 cases of human mesotheliomas and 10 cases of adenocarcinomas were studied by light microscopy, electron microscopy, histochemical and immunohistochemical staining. The results indicated that mesothelioma probably originates from the multipotential subserosal cell which has the features of myofibroblast. In addition to the epithelial, fibrous and mixed types of mesothelioma classified by WHO, poorly differentiated type of mesothelioma can also be found in rats. Electron microscopy, histochemical and immunohistochemical staining are very helpful in differentiating mesotheliomas from adenocarcinomas.}, } @article {pmid1750402, year = {1991}, author = {Boglioli, LR and Taff, ML and Spitz, WU and Gordon, RE}, title = {Sudden death of an elderly man with multiple malignant neoplasms.}, journal = {The American journal of forensic medicine and pathology}, volume = {12}, number = {3}, pages = {265-271}, doi = {10.1097/00000433-199109000-00020}, pmid = {1750402}, issn = {0195-7910}, mesh = {Adenocarcinoma/complications/*pathology ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Colonic Neoplasms/complications/pathology ; Coronary Disease/complications/mortality ; Death, Sudden/*etiology ; Diagnosis, Differential ; Humans ; Male ; Mesothelioma/complications/etiology/*pathology ; Neoplasms, Multiple Primary/complications/*pathology ; Pleural Neoplasms/complications/etiology/*pathology ; Prostatic Neoplasms/complications/pathology ; }, abstract = {With the lengthening of the human life span, cancer has become an increasingly important medical problem for the aged. It is not uncommon to find multiple primary neoplasms in elderly individuals. We recently investigated the death of an elderly man who had died suddenly and had three incidental malignant neoplasms, including a pleural mesothelioma, first diagnosed at autopsy. The importance of performing a complete medicolegal autopsy for epidemiological and statistical purposes is emphasized.}, } @article {pmid2065276, year = {1991}, author = {Chahinian, AP and Kirschner, PA and Gordon, RE and Szrajer, L and Holland, JF}, title = {Usefulness of the nude mouse model in mesothelioma based on a direct patient-xenograft comparison.}, journal = {Cancer}, volume = {68}, number = {3}, pages = {558-560}, doi = {10.1002/1097-0142(19910801)68:3<558::aid-cncr2820680319>3.0.co;2-i}, pmid = {2065276}, issn = {0008-543X}, support = {CA-36283/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Asbestos/adverse effects ; Cisplatin/administration & dosage ; *Disease Models, Animal ; Humans ; Male ; Mesothelioma/*drug therapy/pathology/surgery ; Mice ; *Mice, Nude ; Middle Aged ; Mitomycins/administration & dosage ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasm Transplantation ; Pleural Neoplasms/*drug therapy/pathology/surgery ; }, abstract = {A patient with malignant mesothelioma experienced tumor recurrence 3 months after pleuropneumonectomy. Samples of the tumor were transplanted into nude mice to assess chemosensitivity. There was close concordance between the results in xenografts and the clinical outcome in this patient. Both mitomycin and to a lesser extent cisplatin were effective as single agents against the nude mouse xenografts, and the combination of these two drugs produced a complete response both in the patient and in the xenografts. The patient survived 18 months from onset of chemotherapy and 24 months from diagnosis. The duration of clinical complete response to chemotherapy was 14 months, despite the fact that mitomycin, the most effective agent against the xenografts, was discontinued after only two cycles because the patient developed pulmonary toxicity. This direct patient-xenograft correlation further validates the usefulness of the nude mouse model in the search for effective therapies for malignant mesothelioma, a tumor characterized by frequent refractoriness to most available agents.}, } @article {pmid1953539, year = {1991}, author = {Musk, AW and Dewar, J and Shilkin, KB and Whitaker, D}, title = {Miliary spread of malignant pleural mesothelioma without a clinically identifiable pleural tumour.}, journal = {Australian and New Zealand journal of medicine}, volume = {21}, number = {4}, pages = {460-462}, doi = {10.1111/j.1445-5994.1991.tb01355.x}, pmid = {1953539}, issn = {0004-8291}, mesh = {Adult ; Humans ; Lymph Nodes/pathology ; Lymphatic Metastasis/pathology ; Male ; Mesothelioma/diagnostic imaging/pathology/*secondary ; Pleural Neoplasms/diagnostic imaging/*pathology ; Radiography ; }, abstract = {A 44-year-old man with past minor exposure to blue asbestos presented with supraclavicular lymphadenopathy and miliary shadowing on his chest radiograph. Cytology and electronmicroscopy on material obtained by fine needle aspiration from his cervical lymph node revealed malignant mesothelioma. Malignant mesothelioma cells were also present in bronchoalveolar lavage fluid and on transbronchial lung biopsy. At autopsy the right pleural cavity was studded with small tumour nodules. This case demonstrates that malignant mesothelioma may present as metastatic disease and without evidence on conventional investigations of a primary pleural tumour.}, } @article {pmid1947241, year = {1991}, author = {Brown, RC and Davis, JM and Douglas, D and Gruber, UF and Hoskins, JA and Ilgren, EB and Johnson, NF and Rossiter, CE and Wagner, JC}, title = {Carcinogenicity of the insulation wools: reassessment of the IARC evaluation.}, journal = {Regulatory toxicology and pharmacology : RTP}, volume = {14}, number = {1}, pages = {12-23}, doi = {10.1016/0273-2300(91)90048-z}, pmid = {1947241}, issn = {0273-2300}, mesh = {Animals ; Carcinogens/*toxicity ; *Glass ; Humans ; Neoplasms/chemically induced/epidemiology ; Neoplasms, Experimental/chemically induced/pathology ; }, abstract = {In assessing the health evidence concerning man-made mineral fibers, the chemical composition, surface activity, durability, and size of fibers have to be taken into account. Special-purpose fine glass fibers need to be separated from the insulation wools (glass, rock, and slag wool). The epidemiological evidence is sufficient to conclude that there has been no mesothelioma risk to workers producing or using glass wool, rock wool, or slag wool. The epidemiological studies have been large and powerful, and they show no evidence of a cause-effect relationship between lung cancer and exposure to glass wool, rock wool, or slag wool fibers. There is some evidence of a small cancer hazard attached to the manufacturing process in slag wool plants 20 to 50 years ago, when asbestos was used in some products and other carcinogenic substances were present. However, this hazard is not associated with any index of exposure to slag wool itself. Animal inhalation studies of ordinary insulation wools also show that there is no evidence of hazard associated with exposure to these relatively coarse, soluble fibers. The evidence of carcinogenicity is limited to experiments with special-purpose fine durable glass fibers or experimental fibers, and only when these fibers are injected directly into the pleural or peritoneal cavity. Multiple chronic inhalation studies of these same special-purpose fine glass fibers have not produced evidence of carcinogenicity. It is suggested that the present IARC evaluation of the carcinogenic risk of insulation wools should be revised to Category 3: not classifiable as to carcinogenicity to humans.}, } @article {pmid1892768, year = {1991}, author = {Paci, E and Zappa, M and Paoletti, L and Buiatti, E and Chellini, E and Merler, E and Seniori Costantini, A}, title = {Further evidence of an excess of risk of pleural malignant mesothelioma in textile workers in Prato (Italy).}, journal = {British journal of cancer}, volume = {64}, number = {2}, pages = {377-378}, pmid = {1892768}, issn = {0007-0920}, mesh = {Asbestos/adverse effects ; Female ; Humans ; Italy ; Male ; Mesothelioma/*epidemiology ; Pleural Neoplasms/*epidemiology ; Textile Industry ; }, } @article {pmid1855220, year = {1991}, author = {Funaki, K and Everitt, J and Bermudez, E and Walker, C}, title = {Trisomy of rat chromosome 1 associated with mesothelial cell transformation.}, journal = {Cancer research}, volume = {51}, number = {15}, pages = {4059-4066}, pmid = {1855220}, issn = {0008-5472}, mesh = {Animals ; Cell Line ; Cell Transformation, Neoplastic/*genetics ; Chromosomes/physiology ; Epithelial Cells ; Epithelium/physiology ; Karyotyping ; Mesothelioma/genetics ; Pleura/cytology/physiology ; Rats ; *Trisomy ; Tumor Cells, Cultured ; }, abstract = {Identification of specific chromosomal aberrations in transformed mesothelial cells is an important step in elucidating the mechanism of transformation of these cells which are targets for occupational and environmental carcinogens, such as asbestos fibers. Cytogenetic analysis of normal rat mesothelial cell lines revealed that at late passage (p20-p34), trisomy of chromosome 1 was present in greater than 80% of the cells in four spontaneously immortalized lines examined, whereas at early passage (p8-p10), only 15-44% of the cells had trisomy 1. Trisomy of chromosome 1 had increased in the population as a function of passage, suggesting that cells with trisomy 1 had a selective growth advantage under in vitro culture conditions and that this alteration was associated with transformation. A commercially available rat mesothelial cell line (4/4 RM4, ATCC), was also found to have a duplication of a portion of the long arm of chromosome 1. To determine if chromosome 1 alterations have relevance to the transformed phenotype in vivo, a neoplastic cell line was established from a spontaneous rat mesothelioma. At passage 15, trisomy of chromosome 1 was observed in 26% of the metaphases in this line. However, when these cells were injected into nude mice, 99% of the cells from the resulting tumor contained an additional copy of chromosome 1. Therefore, trisomy 1 also conferred a selective growth advantage in vivo and/or was associated with the malignant subpopulation in the tumor derived cell line. These studies suggest that chromosome 1 contains a gene(s) involved in transformation of rat mesothelial cells.}, } @article {pmid1676096, year = {1991}, author = {Magnani, C and Borgo, G and Betta, GP and Botta, M and Ivaldi, C and Mollo, F and Scelzi, M and Terracini, B}, title = {Mesothelioma and non-occupational environmental exposure to asbestos.}, journal = {Lancet (London, England)}, volume = {338}, number = {8758}, pages = {50}, doi = {10.1016/0140-6736(91)90034-m}, pmid = {1676096}, issn = {0140-6736}, mesh = {Asbestos/*adverse effects ; *Environmental Exposure ; Female ; Humans ; Italy/epidemiology ; Male ; Mesothelioma/epidemiology/*etiology ; Pleural Neoplasms/epidemiology/*etiology ; }, } @article {pmid1942646, year = {1991}, author = {Inase, N and Takayama, S and Nakayama, M and Miura, H and Kimula, Y}, title = {Pleural mesothelioma after neighborhood exposure to asbestos during childhood.}, journal = {Japanese journal of medicine}, volume = {30}, number = {4}, pages = {343-345}, doi = {10.2169/internalmedicine1962.30.343}, pmid = {1942646}, issn = {0021-5120}, mesh = {Adult ; Asbestos/*adverse effects ; Environmental Exposure ; Female ; Humans ; Mesothelioma/*etiology/pathology ; Pleural Neoplasms/*etiology/pathology ; }, abstract = {A 38-year-old woman with pleural mesothelioma who had a history of neighborhood asbestos exposure during her childhood was demonstrated. She had no known history of occupational asbestos exposure. This is the first case of mesothelioma with neighborhood asbestos exposure reported in Japan. Previously-reported cases of mesothelioma with neighborhood asbestos exposure in the English language literature were reviewed.}, } @article {pmid1890486, year = {1991}, author = {Sandén, A and Järvholm, B}, title = {A study of possible predictors of mesothelioma in shipyard workers exposed to asbestos.}, journal = {Journal of occupational medicine. : official publication of the Industrial Medical Association}, volume = {33}, number = {7}, pages = {770-773}, pmid = {1890486}, issn = {0096-1736}, mesh = {Adult ; Aged ; Asbestosis/diagnosis/epidemiology/*etiology ; Cohort Studies ; Cross-Sectional Studies ; Follow-Up Studies ; Forced Expiratory Volume ; Humans ; Incidence ; Male ; Mesothelioma/diagnosis/epidemiology/*etiology ; Middle Aged ; Occupational Diseases/diagnosis/epidemiology/*etiology ; Pleural Neoplasms/diagnosis/epidemiology/*etiology ; Prospective Studies ; Risk Factors ; *Ships ; Smoking/adverse effects ; Sweden/epidemiology ; Vital Capacity ; }, abstract = {In a prospective cohort study of 3893 shipyard workers, we estimated the value of medical monitoring, including chest radiograph, spirometry, and questions about smoking habits, asbestos exposure, and respiratory symptoms, as predictors of the risk of developing mesothelioma. There was no strong association between different exposure parameters and risk of mesothelioma. Impaired lung function and smoking were not predictors of risk of mesothelioma. Pleural plaque was not found to be associated with an increased risk of mesothelioma. Respiratory symptoms were of low value as predictors of risk of mesothelioma. Thus, traditional methods in health monitoring seem to be of low value in identifying persons with a high risk of mesothelioma in populations exposed to asbestos.}, } @article {pmid1721749, year = {1991}, author = {Weidner, N}, title = {Malignant mesothelioma of peritoneum.}, journal = {Ultrastructural pathology}, volume = {15}, number = {4-5}, pages = {515-520}, doi = {10.3109/01913129109016258}, pmid = {1721749}, issn = {0191-3123}, mesh = {Cell Transformation, Neoplastic/pathology/ultrastructure ; Humans ; Immunohistochemistry ; Keratins/analysis ; Male ; Mesothelioma/chemistry/*pathology/ultrastructure ; Microscopy, Electron ; Middle Aged ; Peritoneal Neoplasms/chemistry/*pathology/ultrastructure ; }, abstract = {A 57-year-old man with malaise, ascites, and abdominal pain was found to have a peritoneum studied with numerous, small nodular tumor masses. Light microscopy revealed an anaplastic malignant tumor of uncertain differentiation. Mucin stains were negative. Electron microscopy revealed pleomorphic tumor cells with diffusely distributed cytoplasmic tonofilaments and well-developed true desmosomes. No long, thin, branching microvilli were present, yet tumor cells were strongly positive for both callus keratin (polyclonal) and monoclonal cytokeratin (AE1/3) in a diffuse cytoplasmic distribution (a pattern corresponding to the diffuse cytoplasmic tonofilaments). Tumor cells were negative for Leu-M1 and carcinoembryonic antigen. The findings were most consistent with malignant mesothelioma, and additional questioning, after tissue diagnosis, revealed a work history of asbestos exposure.}, } @article {pmid1646682, year = {1991}, author = {Leigh, J and Rogers, AJ and Ferguson, DA and Mulder, HB and Ackad, M and Thompson, R}, title = {Lung asbestos fiber content and mesothelioma cell type, site, and survival.}, journal = {Cancer}, volume = {68}, number = {1}, pages = {135-141}, doi = {10.1002/1097-0142(19910701)68:1<135::aid-cncr2820680125>3.0.co;2-s}, pmid = {1646682}, issn = {0008-543X}, mesh = {Asbestos/*analysis ; Asbestos, Amosite ; Asbestos, Crocidolite ; Asbestos, Serpentine ; Humans ; Lung/*chemistry/ultrastructure ; Mesothelioma/mortality/*pathology ; Peritoneal Neoplasms/mortality/*pathology ; Pleural Neoplasms/mortality/*pathology ; Survival Rate ; }, abstract = {All ascertainable cases of malignant mesothelioma in Australia were notified to a national surveillance program in the period January 1, 1980 to December 31, 1985. There were 854 cases obtained and 823 confirmed on clinical (77) or histologic (746) ground. Tumor site was known in 759 cases (685 pleural and 74 peritoneal). Lung fiber content analyses by light microscopy and analytic transmission electron microscopy with energy-dispersive x-ray analysis were done on 226 cases in which postmortem material was available, using the method of Rogers. Cell type was determined by a five-member expert panel of pathologists appointed by the Royal College of Pathologists of Australasia. There was a statistically significant trend between lung fiber content (fibers/g dry lung) and cell type from epithelial (low fiber content) through mixed to sarcomatous (high fiber content). This trend was most apparent for total uncoated fibers (chi-square = 6.8, df = 1, P less than 0.01) and crocidolite (chi-square = 6.7, df = 1, P less than 0.01). Lung fiber content also was associated with tumor site; higher lung fiber content being associated with peritoneal tumors. This relationship was significant for all fiber content measures except chrysotile and was independent of the fiber content-cell type relationship (log-linear analysis). Survival from time of provisional diagnosis was significantly longer for epithelial (mean, 13 months; standard deviation [SD], 12.8) and mixed (mean, 10.2 months; SD, 8.7) types than sarcomatous cell types (mean, 5.8 months; SD, 6.5; P less than 0.0001, by analysis of variance on log10 survival time). Survival time was significantly greater for pleural tumors (mean, 11.4 months; SD, 13.4) than peritoneal tumors (mean, 8.6 months; SD, 12.5) (P less than 0.005, by Student's t test on log10 survival time).}, } @article {pmid2064981, year = {1991}, author = {Castleman, BI}, title = {Asbestos and cancer: history and public policy.}, journal = {British journal of industrial medicine}, volume = {48}, number = {6}, pages = {427-432}, pmid = {2064981}, issn = {0007-1072}, mesh = {Asbestos/*adverse effects ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; Occupational Exposure ; Public Policy ; }, } @article {pmid2064978, year = {1991}, author = {Wagner, JC}, title = {The discovery of the association between blue asbestos and mesotheliomas and the aftermath.}, journal = {British journal of industrial medicine}, volume = {48}, number = {6}, pages = {399-403}, pmid = {2064978}, issn = {0007-1072}, mesh = {Asbestos/*adverse effects ; Female ; History, 20th Century ; Humans ; Lung Neoplasms/*etiology/history ; Male ; Mesothelioma/*etiology/history ; Occupational Diseases/*etiology/history ; Occupational Health/history ; Risk Factors ; South Africa ; }, abstract = {As this is the 30th anniversary of the publication of our paper "Diffuse pleural mesotheliomas and asbestos exposure in the north west Cape Province," and 1 December 1990 is the first anniversary of John Gilson's death, I think it is appropriate to subunit this paper. It covers the background of the discovery of the series of mesotheliomas in the north western region of the Cape Province, and the subsequent publication, which has become the most cited paper in industrial medicine. It was John Gilson who directed the next phase, which substantiated this discovery. He clarified the situation in his summary of the report to the director of the International Agency for Research in Cancer in 1972. This I have quoted in full and have had the temerity to update to 1990. I am sure that many will want to elaborate these views, and I hope that they will submit their opinions to this journal.}, } @article {pmid1924208, year = {1991}, author = {Brockmann, M}, title = {[Asbestos-associated lung and pleural diseases--pathological anatomy].}, journal = {Pneumologie (Stuttgart, Germany)}, volume = {45}, number = {6}, pages = {422-428}, pmid = {1924208}, issn = {0934-8387}, mesh = {Asbestosis/classification/*pathology ; Humans ; Lung/*pathology ; Lung Neoplasms/etiology/pathology ; Mesothelioma/classification/pathology ; Pleura/*pathology ; Pleural Neoplasms/etiology/pathology ; }, } @article {pmid1924207, year = {1991}, author = {Konietzko, N}, title = {[Asbestos-induced pleuropulmonary diseases].}, journal = {Pneumologie (Stuttgart, Germany)}, volume = {45}, number = {6}, pages = {417-421}, pmid = {1924207}, issn = {0934-8387}, mesh = {Asbestosis/*physiopathology ; Bronchial Neoplasms/etiology ; Carcinogens ; Humans ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; *Occupational Exposure ; Pleural Diseases/etiology ; Pleural Neoplasms/etiology ; Pleurisy/etiology ; }, } @article {pmid1876895, year = {1991}, author = {Aggarwal, P and Wali, JP and Agarwal, J}, title = {Pericardial mesothelioma presenting as a mediastinal mass.}, journal = {Singapore medical journal}, volume = {32}, number = {3}, pages = {185-186}, pmid = {1876895}, issn = {0037-5675}, mesh = {Adult ; Diagnosis, Differential ; Heart Neoplasms/*diagnosis ; Humans ; Male ; Mediastinal Cyst/*diagnosis ; Mesothelioma/*diagnosis ; *Pericardium ; Tomography Scanners, X-Ray Computed ; }, abstract = {A case of malignant mesothelioma of the pericardium, who presented with an anterior mediastinal mass, is reported. Such a presentation of the pericardial mesothelioma is distinctly rare. As in most of the other reported cases, our patient also did not have any exposure to asbestos. The diagnosis in the present case was established after surgery. Most of the cases reported in the literature, were diagnosed only at postmortem. The treatment of choice is surgical resection of the tumour. The prognosis of pericardial mesothelioma is poor and till now, only two long survivals have been reported.}, } @article {pmid1843255, year = {1991}, author = {Davis, JM and Bolton, RE and Miller, BG and Niven, K}, title = {Mesothelioma dose response following intraperitoneal injection of mineral fibres.}, journal = {International journal of experimental pathology}, volume = {72}, number = {3}, pages = {263-274}, pmid = {1843255}, issn = {0959-9673}, mesh = {Animals ; Asbestos/administration & dosage/classification/*toxicity ; Dose-Response Relationship, Drug ; Injections, Intraperitoneal ; Mesothelioma/*etiology ; Particle Size ; Peritoneal Neoplasms/*etiology ; Proportional Hazards Models ; Rats ; Risk ; }, abstract = {The relationship between injected dose and the development of peritoneal mesotheliomas has been examined in rats using the UTCC standard reference samples of chrysotile, crocidolite and amosite as well as a sample of fibrous erionite from Oregon. Doses injected into the peritoneal cavity ranged from 0.005 to 25 mg and with each dust a clear dose response was found. The proportion of animals developing tumours increased with the amount of dust injected while the tumour induction period was reduced. When times to death from mesothelioma were analysed using standard hazard models, erionite was the most carcinogenic dust by mass followed by chrysotile, amosite and crocidolite. The hazard slopes for erionite, chrysotile and crocidolite, over the range of doses examined, were parallel while the slope for amosite was shallower. The relative hazards for the various dust types were also examined with dose expressed as the number of injected fibres in a range of sizes as measured by SEM. No combination of fibre dimensions was found at which the hazard for the four dust types was equal although when dose was expressed as the number of long fibres injected (> 8 microns in length) the hazard slopes for chrysotile, crocidolite and amosite were relatively close. The hazard level of erionite remained well above the other dust types regardless of how the dose was expressed.}, } @article {pmid1710103, year = {1991}, author = {Falconieri, G and Grandi, G and DiBonito, L and Bonifacio-Gori, D and Giarelli, L}, title = {Intracranial metastases from malignant pleural mesothelioma. Report of three autopsy cases and review of the literature.}, journal = {Archives of pathology & laboratory medicine}, volume = {115}, number = {6}, pages = {591-595}, pmid = {1710103}, issn = {0003-9985}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Brain Neoplasms/*secondary ; Female ; Humans ; Keratins/analysis ; Male ; Mesothelioma/chemistry/etiology/*pathology ; Middle Aged ; Neoplasm Metastasis ; Pleural Neoplasms/chemistry/etiology/*pathology ; Vimentin/analysis ; }, abstract = {We report three cases of brain metastases from malignant pleural mesothelioma that were seen at autopsy. We present a summarized review of 15 similar reports that were previously published. Our study included three aged male patients with a long occupational history of heavy asbestos exposure. In two patients, the metastases were discovered incidentally at autopsy, and there were no neurologic symptoms referred to before death. In the other patient, who had clinically occult mesothelioma, the intracranial tumor was discovered ante mortem: in this patient, the clinical features, as well as a computed tomographic scan, suggested a primary tumor of the brain. Interestingly, the histologic features of the latter case that were seen at autopsy depicted a spindle cell tumor that focally exhibited pseudopalisading, necrosis, vascular buds, which deceptively recalled a glioblastoma. All the three cases shared a basic sarcomatous pattern of malignant pleural mesothelioma in both primary and metastatic tumors. The immunohistochemical profile was consistent with such interpretation. It was concluded that metastases to the brain from malignant pleural mesothelioma, although rare, are not exceptional even if their clinical relevance is not prominent. They are seen concomitantly with high-grade tumors, and by mimicking a primary tumor on a clinical, instrumental, and histologic ground, they may occasionally represent a potential source of diagnostic pitfall.}, } @article {pmid2043801, year = {1991}, author = {Morgan, WK}, title = {Mesothelioma and exposure to asbestos.}, journal = {BMJ (Clinical research ed.)}, volume = {302}, number = {6785}, pages = {1153}, pmid = {2043801}, issn = {0959-8138}, mesh = {Asbestos/*adverse effects ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Risk Factors ; }, } @article {pmid2039746, year = {1991}, author = {Fischbein, A and Luo, JC and Pinkston, GR}, title = {Asbestosis, laryngeal carcinoma, and malignant peritoneal mesothelioma in an insulation worker.}, journal = {British journal of industrial medicine}, volume = {48}, number = {5}, pages = {338-341}, pmid = {2039746}, issn = {0007-1072}, mesh = {Aged ; Alcohol Drinking/adverse effects ; Asbestos/adverse effects ; Asbestosis/*complications ; Carcinoma, Squamous Cell/*complications/etiology ; Humans ; Laryngeal Neoplasms/*complications/etiology ; Male ; Mesothelioma/*complications/etiology ; Neoplasms, Multiple Primary/*complications ; Occupational Exposure ; Peritoneal Neoplasms/*complications/etiology ; Smoking/adverse effects ; }, abstract = {Asbestos associated diseases consist of both benign and malignant conditions. A rare constellation of asbestosis, laryngeal carcinoma, and malignant peritoneal mesothelioma occurring in a patient with long term occupational exposure to airborne asbestos fibres is presented. The observation illustrates the powerful disease-causing potential of occupational exposure to asbestos. A brief discussion of multiple primary neoplasms associated with exposure to asbestos is also presented.}, } @article {pmid2039741, year = {1991}, author = {Meredith, SK and Taylor, VM and McDonald, JC}, title = {Occupational respiratory disease in the United Kingdom 1989: a report to the British Thoracic Society and the Society of Occupational Medicine by the SWORD project group.}, journal = {British journal of industrial medicine}, volume = {48}, number = {5}, pages = {292-298}, pmid = {2039741}, issn = {0007-1072}, mesh = {Acute Disease ; Adult ; Asthma/epidemiology/etiology ; Data Collection/methods ; Female ; Humans ; Incidence ; Lung Diseases/epidemiology/etiology ; Male ; Middle Aged ; Occupational Diseases/*epidemiology ; Population Surveillance ; Respiratory Tract Diseases/*epidemiology ; Societies, Medical ; United Kingdom/epidemiology ; }, abstract = {A voluntary scheme for the surveillance of work related and occupational respiratory disease (SWORD) was established in January 1989 with help from the British Thoracic Society and the Society of Occupational Medicine and support from the Health and Safety Executive. Three hundred and fifty four chest physicians representing 90% of the chest clinics in the United Kingdom and 361 occupational physicians submit reports regularly of newly diagnosed cases of work related respiratory illness with information on age, sex, residence, occupation, and suspected causal agent. In 1989 2101 cases were notified, of which frequent diagnoses were asthma (26%), mesothelioma (16%), pneumoconiosis (15%), benign pleural disease (11%), and allergic alveolitis (6%). Incidence rates calculated against denominators from the Labour Force Survey showed very large differences between occupational groups, especially for asthma and asbestos related diseases. Substantial regional variation in the incidence of asthma was not explained by the geographical distribution of high risk industries and was probably due to differing levels of ascertainment. The results imply that the true frequency of acute occupational respiratory disease in the United Kingdom may have been three times greater than that reported.}, } @article {pmid2019171, year = {1991}, author = {Constantopoulos, SH and Theodoracopoulos, P and Dascalopoulos, G and Saratzis, N and Sideris, K}, title = {Metsovo lung outside Metsovo. Endemic pleural calcifications in the ophiolite belts of Greece.}, journal = {Chest}, volume = {99}, number = {5}, pages = {1158-1161}, doi = {10.1378/chest.99.5.1158}, pmid = {2019171}, issn = {0012-3692}, mesh = {Aged ; Asbestos/*adverse effects ; *Asbestos, Amphibole ; Asbestosis/*epidemiology ; Calcinosis/*epidemiology ; *Environmental Exposure ; Greece/epidemiology ; Humans ; Incidence ; Mesothelioma/epidemiology ; Middle Aged ; Pleural Diseases/*epidemiology ; Pleural Neoplasms/epidemiology ; Silicic Acid/adverse effects ; Soil ; }, abstract = {Endemic PCs and high incidence of malignant mesothelioma from household use of asbestos have been reported in Metsovo in northwestern Greece ("Metsovo lung"). In the present study, we present similar findings in six more areas of Greece. Like Metsovo, all these areas are located within ophiolite belts. Like Metsovo, material similar to "Metsovo whitewash" has been used for various domestic uses. Asbestos fibers (chrysotile, antigorite and tremolite) were found in three of the six areas. Also, in two, MPM has been diagnosed. These findings suggest that "Metsovo lung" occurs in several areas of Greece and has similar etiology and epidemiology.}, } @article {pmid2015590, year = {1991}, author = {Muscat, JE and Wynder, EL}, title = {Cigarette smoking, asbestos exposure, and malignant mesothelioma.}, journal = {Cancer research}, volume = {51}, number = {9}, pages = {2263-2267}, pmid = {2015590}, issn = {0008-5472}, support = {CA 17613/CA/NCI NIH HHS/United States ; CA32617/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Case-Control Studies ; Female ; Humans ; Male ; Mesothelioma/epidemiology/*etiology ; Middle Aged ; Occupational Diseases/epidemiology/*etiology ; Peritoneal Neoplasms/epidemiology/*etiology ; Pleural Neoplasms/epidemiology/*etiology ; Risk Factors ; Smoking/*adverse effects ; }, abstract = {In a hospital-based case-control study of 124 (105 male and 19 female) histologically confirmed malignant mesothelioma cases and age- and sex-matched controls, the role of cigarette smoking and the risk of asbestos exposure was investigated. Exposure to asbestos for at least 1 year was likely for 78% of male cases and 16% of female cases, and 90% of males were possibly exposed. Male cases worked predominantly in the ship-building industry, construction, or insulation trades. Elevated risks were found for males employed in asbestos-related industries [odds ratio (OR) 8.1; 95% confidence interval (CI) 4.9-13.5], e.g., shipyards (OR 82.9, 95% CI 25.5-269.1), construction/maintenance (OR 8.3, 95% CI 4.6-14.8), and other asbestos-related jobs (OR 3.2, 95% CI 1.4-7.2), and for males who self-reported exposure to asbestos or insulation (OR 50.9, 95% CI 21.7-119.8). A statistically significant trend was found for the risk of mesothelioma with increasing years employed in non-shipyard asbestos-related occupations. Among women, only one case worked in an asbestos-related industry and two reported domestic contact with asbestos. No association between cigarette smoking and mesothelioma was found for either men or women. We also report the occurrence of mesothelioma in occupations which have not been previously reported.}, } @article {pmid2013045, year = {1991}, author = {Hillerdal, G and Lindqvist, U and Engström-Laurent, A}, title = {Hyaluronan in pleural effusions and in serum.}, journal = {Cancer}, volume = {67}, number = {9}, pages = {2410-2414}, doi = {10.1002/1097-0142(19910501)67:9<2410::aid-cncr2820670933>3.0.co;2-d}, pmid = {2013045}, issn = {0008-543X}, mesh = {Aged ; Biomarkers, Tumor/analysis ; Exudates and Transudates/*metabolism ; Female ; Heart Diseases/complications ; Humans ; Hyaluronic Acid/*analysis ; Male ; Mesothelioma/complications/*metabolism ; Middle Aged ; Neoplasm Metastasis ; Pleural Effusion/blood/etiology/*metabolism ; Pleural Neoplasms/complications/*metabolism/secondary ; }, abstract = {It has been suggested that a high level of hyaluronan (hyaluronic acid, HYA) in pleural fluid is an indicator of malignant mesothelioma. In 78 consecutive patients with pleural effusion of various causes the HYA concentration was measured in pleural fluid samples and in serum. Nine patients had malignant pleural mesothelioma, and in three of them the HYA level in pleural fluid was 100 mg/l or more. In 42 patients with effusions due to metastatic malignancy, the mean HYA in the pleural fluid was 75 mg/l, and in five the HYA level was above 100 mg/l. Cardiac insufficiency caused the effusion in 11 patients, of whom two had a level above 100 mg/l in pleural fluid. Four patients had a serologically confirmed viral infection and had HYA levels in pleural fluid of 8, 157, 335, and 554 mg/l, respectively. One patient had postinfectious effusion with an HYA level in pleural exudate of 748 mg/l, the highest in this investigation. Two patients had benign asbestos pleural effusions, and both had high pleural HYA levels (256 and 490 mg/l, respectively). The serum HYA values were much lower than in the pleural fluid, namely from 15 to 480 micrograms/l; the levels were independent of the levels in the pleural fluid. Thus, a high level of HYA in pleural fluid is not specific for mesothelioma but can occur in other malignant or benign diseases, and a low level does not exclude mesothelioma.}, } @article {pmid2024254, year = {1991}, author = {Orn, S and Odden, S and Osnes, M}, title = {[Familial clustering of asbestos-related diseases].}, journal = {Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke}, volume = {111}, number = {9}, pages = {1099-1101}, pmid = {2024254}, issn = {0029-2001}, mesh = {Aged ; Asbestos/*adverse effects ; Asbestosis/*etiology/genetics ; Carcinoma, Bronchogenic/*chemically induced/genetics ; Environmental Exposure ; Female ; Humans ; Lung Neoplasms/*chemically induced/genetics ; Male ; Mesothelioma/*chemically induced/genetics ; Middle Aged ; Norway ; Occupational Exposure ; Peritoneal Neoplasms/*chemically induced/genetics ; }, abstract = {This article describes the case histories of four individuals in the same family, all of whom developed asbestos-related disease. Special emphasis is placed upon the case of a woman, who after seemingly minimal exposure to asbestos, in the form of cleaning her husband's working clothes, developed a malignant mesothelioma. The incidence of asbestos-related disease has increased steadily over the past ten years. This probably reflects the extensive use of asbestos in Norway since World War II, and the long latency period of the disease. The authors recommend obtaining an in-depth history of exposure when asbestos-related disease is suspected.}, } @article {pmid2069994, year = {1991}, author = {Ruffie, PA}, title = {Pleural mesothelioma.}, journal = {Current opinion in oncology}, volume = {3}, number = {2}, pages = {328-334}, doi = {10.1097/00001622-199104000-00014}, pmid = {2069994}, issn = {1040-8746}, mesh = {Humans ; *Mesothelioma/etiology/pathology/therapy ; *Pleural Neoplasms/etiology/pathology/therapy ; }, abstract = {Pleural mesotheliomas are uncommon tumors that can be classified as localized or diffuse. Diffuse pleural mesotheliomas are invariably malignant. Although the frequency is low in the general population, it is more common in persons with a heavy occupational exposure to asbestos, and is considered as a signal tumor to asbestos exposure with medicolegal consequences. Mesothelioma incidence has been steadily rising during the past two decades, reflecting the increase in asbestos exposure during and following World War II. Clinical features include initial complaints of nonpleuritic chest pain and dyspnea. Distinguishing malignant mesothelioma from metastatic adenocarcinoma can be difficult, and can require large tissue biopsy with special stains and electron microscopy. The median survival of about 9 to 12 months confirms the poor outcome of pleural mesothelioma. The clinical deterioration is primarily attributable to locoregional spread of tumors, but metastasis is not rare. Several factors seem to have a prognostic value: performance status, stage, platelet count, age, histologic subtype, and asbestos exposure. In spite of the different therapeutic modalities such as surgery, radiotherapy, and chemotherapy used alone or in combination, the median survival is fairly different from survival among untreated patients. Because of the uncommon occurrence of this tumor and the existence of several different prognostic categories, a cooperative effort will be necessary for future therapeutic trials. If these active new therapies are identified, it would be useful to compare them to a best supportive care regimen in order to demonstrate an advantage of the treatment.}, } @article {pmid2025587, year = {1991}, author = {Hughes, JM and Weill, H}, title = {Asbestosis as a precursor of asbestos related lung cancer: results of a prospective mortality study.}, journal = {British journal of industrial medicine}, volume = {48}, number = {4}, pages = {229-233}, pmid = {2025587}, issn = {0007-1072}, mesh = {Adult ; Aged ; Asbestosis/*complications/diagnostic imaging/mortality ; Cohort Studies ; Humans ; Incidence ; Louisiana/epidemiology ; Lung/diagnostic imaging ; Lung Neoplasms/diagnostic imaging/epidemiology/*etiology/mortality ; Male ; Mesothelioma/mortality ; Middle Aged ; Prospective Studies ; Radiography ; Risk Factors ; Smoking/adverse effects ; }, abstract = {A prospective mortality study of 839 men employed in the manufacture of asbestos cement products in 1969 examined lung cancer risk in relation to lung fibrosis seen on chest x ray film, controlling for age, smoking, and exposure to asbestos. Twenty or more years after hire, no excess of lung cancer was found among workers without radiographically detectable lung fibrosis, even among long term workers (greater than or equal to 21.5 years); nor was there a trend in risk by level of cumulative exposure to asbestos among such workers. By contrast, employees with small opacities (greater than or equal to 1/0; ILO classification) experienced a significantly raised risk of lung cancer (nine observed deaths v 2.1 expected), even though their exposures to asbestos were similar to the exposures of long term workers without opacities. In this population, excess risk of lung cancer was restricted to workers with x ray film evidence of asbestosis, a finding consistent with the view that asbestos is a lung carcinogen because of its fibrogenicity.}, } @article {pmid1958874, year = {1991}, author = {Morinaga, K and Hanai, A and Fujimoto, I and Ohtsuka, J and Matsumura, T and Sakato, J and Hara, I and Yokoyama, K and Sera, Y}, title = {[A retrospective cohort study of workers in small asbestos industries in south Osaka].}, journal = {[Nihon koshu eisei zasshi] Japanese journal of public health}, volume = {38}, number = {4}, pages = {267-271}, pmid = {1958874}, issn = {0546-1766}, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Asbestosis/*mortality ; Cohort Studies ; Female ; Follow-Up Studies ; Humans ; Japan/epidemiology ; Lung Neoplasms/*mortality ; Male ; Middle Aged ; *Physical Examination ; Retrospective Studies ; Sex Factors ; }, abstract = {A retrospective cohort study was carried out on asbestos workers who had received health examinations in 1972 to 1974 conducted by the Osaka Health Center. The subjects, total of 789 (329 males, 460 females) were followed-up for 10 years (Jan. 1, 1975-Dec. 31, 1984). There were sixty-one deaths in the cohort--4 tuberculosis, 12 malignant neoplasms (4 stomach cancers, 8 respiratory cancers including one case of pleural mesothelioma), 18 circulatory diseases, 24 respiratory diseases, and 3 other causes of death. Standardized mortality ratio (SMR) was calculated age and sex-specific death rates for the general population in Osaka between 1975-79 and 1980-84. SMR for all causes of death, stomach cancer, respiratory cancer, circulatory diseases, and respiratory diseases were 1.15, 3.29, 0.75, 3.88, 0.93 and 8.63 respectively. Respiratory cancer and respiratory diseases showed statistically significant (p less than 0.01) excess death with a mean death age of 59 and 56 years old respectively.}, } @article {pmid1876592, year = {1991}, author = {Woitowitz, HJ and Grossgarten, K}, title = {[Pleural mesothelioma: etiology and practical consequences].}, journal = {Pneumologie (Stuttgart, Germany)}, volume = {45}, number = {4}, pages = {153-158}, pmid = {1876592}, issn = {0934-8387}, mesh = {Asbestos/*adverse effects ; Asbestosis/complications ; Dust/*adverse effects ; Humans ; Occupational Diseases/*etiology ; Pleural Neoplasms/*etiology ; Risk Factors ; }, abstract = {In the course of the past few decades there has been a heavy world-wide increase in the incidence of mesotheliomas among the industrialised nations. A characteristic feature of this is an extremely great difference in respect of the expected incidence of the tumour between persons who had been in contact--even though a long time back--with asbestos fibre dust, or who worked or resided near sources of asbestos emission, or who had contact with asbestos fibres in their household, on the one hand, and with the rest of the population on the other. Hence, pleuromesothelioma is not only a tumour signalling the risk brought about by the presence of asbestos or of zeolites in the environment, it is also so to say the environmental tumour par excellence. Among the members of those artisan professions where products containing asbestos are being employed, pleuromesotheliomas have been a far more frequent source of professionally conditioned cancer than among the workers of the asbestos industry proper. Since the latency period is as a rule 30 years, the physician must go back scrupulously 20 to 60 years in the patient's previous history to find out whether there had been an exposure to asbestos at any time that would induce tumour formation, the more so since a mere couple of weeks' exposure can be enough to induce a tumour so many years later. On account of the pleurotropy of inhaled asbestos fibres, pointers to an asbestosis of the lungs and/or pleura should be followed up on-target. Further practical consequences are discussed.}, } @article {pmid1865600, year = {1991}, author = {Nakazawa, H and Kurosawa, H and Nakayama, K and Tsuburaya, T and Watanabe, H and Hayashi, M and Matsuoka, T and Shimura, S}, title = {[A case of malignant pleural mesothelioma presenting as pneumothorax].}, journal = {Nihon Kyobu Shikkan Gakkai zasshi}, volume = {29}, number = {4}, pages = {477-481}, pmid = {1865600}, issn = {0301-1542}, mesh = {Diagnosis, Differential ; Female ; Humans ; Mesothelioma/complications/*diagnosis ; Middle Aged ; Pleural Effusion/*diagnosis/etiology ; Pleural Neoplasms/complications/*diagnosis ; Pneumothorax/*diagnosis/etiology ; Radiography, Thoracic ; Tomography, X-Ray Computed ; }, abstract = {The patient was a 51-year-old woman who had no history of asbestos exposure and showed left pneumothorax with a small amount of pleural effusion. On admission to our hospital, she showed clinical and laboratory data similar to that of spontaneous pneumothorax except for a high concentration of hyaluronic acid in pleural fluid. After treatment of pneumothorax, pleural effusion appeared to decrease on chest X-ray. After 3 months, however, pleural effusion again increased, in spite of the improvement of pneumothorax. The patient received open lung biopsy and the histological examination showed mixed type malignant pleural mesothelioma.}, } @article {pmid1852926, year = {1991}, author = {Ilgren, EB and Wagner, JC}, title = {Background incidence of mesothelioma: animal and human evidence.}, journal = {Regulatory toxicology and pharmacology : RTP}, volume = {13}, number = {2}, pages = {133-149}, doi = {10.1016/0273-2300(91)90018-q}, pmid = {1852926}, issn = {0273-2300}, mesh = {Animals ; Asbestos/toxicity ; Humans ; Lung Neoplasms/epidemiology/etiology ; Mesothelioma/*epidemiology/etiology ; }, abstract = {Evidence is presented showing that mesotheliomas can have causes other than exposure to asbestos dust, in both experimental animals and humans. In experimental animals, for example, results from two major experimental laboratories suggest that at least 10% may be taken for background incidence, whereas a third laboratory suggests that the experimental group must have a rate exceeding 30% "Background" also includes mesotheliomas found in association with nonfibrous and fibrous nonasbestiform agents. Mesotheliomas in humans can be broadly classified in a manner similar to those of experimental animals: (1) spontaneously occurring, (2) those with a latent period less than 10 years, (3) childhood mesotheliomas, (4) familial cases, (5) cases before the 20th century, (6) mineralogically negative mesotheliomas, and (7) mesotheliomas caused by nonasbestiform agents. The importance of the acceptance of these "background" cases lies in the fact that a basis is provided for the study of the incidence of disease associated with various types of asbestos.}, } @article {pmid1852925, year = {1991}, author = {Ilgren, EB and Browne, K}, title = {Asbestos-related mesothelioma: evidence for a threshold in animals and humans.}, journal = {Regulatory toxicology and pharmacology : RTP}, volume = {13}, number = {2}, pages = {116-132}, doi = {10.1016/0273-2300(91)90017-p}, pmid = {1852925}, issn = {0273-2300}, mesh = {Animals ; Asbestos/*toxicity ; Carcinogenicity Tests ; Humans ; Mesothelioma/*etiology ; }, abstract = {A threshold for mesothelioma for the major asbestos fiber types becomes not only plausible but also very likely in view of the existence of a distinct background incidence of spontaneously occurring and non-asbestos-related mesotheliomas; the high occupational doses associated with the appearance of mesotheliomas in humans; and the large number of "tumorigenic" fibers required to produce significant numbers of mesotheliomas in animals. Even when the duration of exposure associated with the appearance of mesotheliomas in humans has been brief, the exposure itself has been intense. The review of the relevant animal and human literature cited herein supports the concept of mesothelioma threshold.}, } @article {pmid1848472, year = {1991}, author = {Rogers, AJ and Leigh, J and Berry, G and Ferguson, DA and Mulder, HB and Ackad, M}, title = {Relationship between lung asbestos fiber type and concentration and relative risk of mesothelioma. A case-control study.}, journal = {Cancer}, volume = {67}, number = {7}, pages = {1912-1920}, doi = {10.1002/1097-0142(19910401)67:7<1912::aid-cncr2820670716>3.0.co;2-y}, pmid = {1848472}, issn = {0008-543X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects/*analysis ; Asbestos, Amosite ; Asbestos, Crocidolite ; Asbestos, Serpentine ; Case-Control Studies ; Female ; Humans ; Male ; Mesothelioma/*etiology ; Middle Aged ; Particle Size ; }, abstract = {Lung tissue from 221 definite and probable cases of malignant mesothelioma reported to the Australian Mesothelioma Surveillance Program from January 1980 through December 1985 and from an age-sex frequency matched control series of 359 postmortem cases were examined by light microscopic (LM) and analytical transmission electron microscopic (TEM) analysis and energy dispersive x-ray analysis (EDAX). Concentrations of total fibers (coated and uncoated) (LM), crocidolite, amosite, chrysotile, and unidentified amphibole (TEM) (fibers/g dry lung tissue) were measured. Fiber concentrations less than 10 microns in length and greater than or equal to 10 microns in length were separately quantified. By comparing cases (221) and controls (359 LM, 103 TEM), odds ratios for increasing fiber concentrations compared with less than 15,000 fibers/g (LM) and less than 200,000 fibers/g (TEM) (the respective detection limits) were calculated. Univariate analyses showed statistically significant dose-response relationships between odds ratio and fiber concentration for all fiber concentration measures. The relationship between log(odds ratio) and log(fiber concentration) was linear. Multiple logistic regression analysis showed that a model containing crocidolite greater than or equal to 10 microns, amosite less than 10 microns, and chrysotile less than 10 microns as explanatory variables best described the data. The odds ratios for a X10 increase in fiber concentration (fibers/micrograms) were as follows: crocidolite greater than or equal to 10 microns, 29.4 (95% confidence interval [CI], 3.6 to 241); chrysotile less than 10 microns, 15.7 (95% CI, 6.1 to 40); amosite less than 10 microns, 2.3 (95% CI, 1.0 to 5.3). An additive risk model gave similar results. In a subgroup of cases and controls with only chrysotile in the lungs, a significant trend in odds ratio with increasing fiber content was found.}, } @article {pmid2067137, year = {1991}, author = {Yoshimura, H and Takemoto, K}, title = {[Effect of cigarette smoking and/or N-bis(2-hydroxypropyl)nitrosamine (DHPN) on the development of lung and pleural tumors in rats induced by administration of asbestos].}, journal = {Sangyo igaku. Japanese journal of industrial health}, volume = {33}, number = {2}, pages = {81-93}, doi = {10.1539/joh1959.33.81}, pmid = {2067137}, issn = {0047-1879}, mesh = {Adenocarcinoma/etiology ; Animals ; Asbestosis/*complications ; *Carcinogens ; *Cocarcinogenesis ; Lung Neoplasms/*etiology ; Male ; Mesothelioma/etiology ; Nitrosamines/*toxicity ; Pleural Neoplasms/*etiology ; Rats ; Rats, Inbred Strains ; Smoking/*adverse effects ; }, abstract = {Occupationally induced lung cancer and mesothelioma have long been attributed to asbestos and moreover, several epidemiological studies have indicated a co-carcinogenic effect of cigarette smoking on the incidence of lung cancer in asbestos workers. The aim of the present study was to investigate the co-carcinogenic effects of asbestos and other carcinogens with emphasis placed on determining the effects of cigarette smoking on the incidence of asbestos induced carcinomas. Doses of 15 mg of chrysotile asbestos were administered intratracheally to Wistar rats alone and in conjunction with N-bis(hydroxypropyl)nitrosamine (DHPN) and/or cigarette smoking. DHPN at dose of 1 g/kg/B.W. was injected three times intraperitoneally, and the subject animals were exposed to smoke from 10 cigarettes per day, six days a week, for their entire life span. As a result, lung carcinomas were induced in one out of the 31 rats receiving only asbestos. Lung tumors were induced at a much higher incidence in the groups receiving DHPN alone and in conjunction with asbestos: of the 37 rats treated with DHPN alone 19 (51.4%) developed lung tumors, whereas those receiving asbestos as well showed an incidence of 68.4% (23/38) of carcinomas. The development of lung carcinomas (including adenocarcinomas, epidermoid carcinomas, anaplastic carcinomas, and combined carcinomas) was seen in 8 (21.6%) out of the 37 rats receiving DHPN alone and in 23 (60.5%) out of the 38 rats receiving asbestos as well. The incidence of lung carcinoma was significantly increased in combined treatment with asbestos than DHPN alone. In the group receiving asbestos in combination with cigarette smoke, 4 (13.8%) out of the 29 rats developed lung carcinomas, but these carcinomas were more common than in the group receiving only asbestos. Moreover, in the group administered asbestos, DHPN and smoking combined, lung tumors developed in 18 (62.1%) out of the 29, 15 (51.7%) of which proved to be malignant. Mesothelioma (pleura) was induced in three groups in the following combinations: DHPN plus asbestos, 8/38 (21.1%); smoking plus asbestos, 2/29 (6.9%); and smoking, DHPN and asbestos, 4/29 (13.8%). These tumors were extensively located, that is, on the parietal pleura, visceral pleura, epicardium and diaphragm surface. However, mesothelioma was not induced by asbestos alone nor by DHPN alone. Carcinogenicity of asbestos for pleural tumors was significantly promoted by combined treatment with DHPN to an extent greater than DHPN alone. It should be noted that asbestos plus smoking resulted in a higher incidence of mesothelioma than asbestos alone.(ABSTRACT TRUNCATED AT 400 WORDS)}, } @article {pmid2028689, year = {1991}, author = {Leiman, G}, title = {Asbestos bodies in fine needle aspirates of lung masses. Markers of underlying pathology.}, journal = {Acta cytologica}, volume = {35}, number = {2}, pages = {171-174}, pmid = {2028689}, issn = {0001-5547}, mesh = {Asbestosis/diagnosis/*pathology ; Biopsy, Needle/methods ; Lung/*pathology ; Lung Diseases/diagnosis/*pathology ; Lung Neoplasms/diagnosis/*pathology ; Retrospective Studies ; }, abstract = {Analysis of 52 transthoracic-mass aspirates that contained asbestos bodies (ABs) showed the mass to be due to pathology other than (or superimposed upon) asbestosis in every case. Malignancy accounted for 30 masses, all of which were carcinomas except for one mesothelioma. The remaining 22 lesions were benign, with tuberculosis or lung abscesses accounting for the majority. Fine needle aspiration (FNA) detection of the pathology (benign or malignant) associated with ABs was diminished, probably due to asbestos-induced fibrosis. Other diagnostic methods, including bronchial studies, mediastinoscopy and even exploratory thoracotomy, were required to document 20% of the neoplasms and 50% of the benign lesions. The results of this series support the view that ABs in FNA specimens from localized or dominant parenchymal lung masses are significant markers of underlying pathology, whether or not cellular evidence of that pathology is observed in the aspirated material.}, } @article {pmid2015204, year = {1991}, author = {Simonato, L and Fletcher, AC and Andersen, A and Anderson, K and Becker, N and Chang-Claude, J and Ferro, G and Gérin, M and Gray, CN and Hansen, KS}, title = {A historical prospective study of European stainless steel, mild steel, and shipyard welders.}, journal = {British journal of industrial medicine}, volume = {48}, number = {3}, pages = {145-154}, pmid = {2015204}, issn = {0007-1072}, mesh = {Europe/epidemiology ; Humans ; Incidence ; Lung Neoplasms/etiology/mortality ; Male ; Neoplasms/epidemiology/etiology/*mortality ; Occupational Diseases/etiology/*mortality ; Occupational Exposure/*adverse effects ; Prospective Studies ; *Stainless Steel ; Steel ; *Welding ; }, abstract = {A multicentre cohort of 11,092 male welders from 135 companies located in nine European countries has been assembled with the aim of investigating the relation of potential cancer risk, lung cancer in particular, with occupational exposure. The observation period and the criteria for inclusion of welders varied from country to country. Follow up was successful for 96.9% of the cohort and observed numbers of deaths (and for some countries incident cancer cases) were compared with expected numbers calculated from national reference rates. Mortality and cancer incidence ratios were analysed by cause category, time since first exposure, duration of employment, and estimated cumulative dose to total fumes, chromium (Cr), Cr VI, and nickel (Ni). Overall a statistically significant excess was reported for mortality from lung cancer (116 observed v 86.81 expected deaths, SMR = 134). When analysed by type of welding an increasing pattern with time since first exposure was present for both mild steel and stainless steel welders, which was more noticeable for the subcohort of predominantly stainless steel welders. No clear relation was apparent between mortality from lung cancer and duration of exposure to or estimated cumulative dose of Ni or Cr. Whereas the patterns of lung cancer mortality in these results suggest that the risk of lung cancer is higher for stainless steel than mild steel welders the different level of risk for these two categories of welding exposure cannot be quantified with precision. The report of five deaths from pleural mesothelioma unrelated to the type of welding draws attention to the risk of exposure to asbestos in welding activities.}, } @article {pmid2009740, year = {1991}, author = {Aberle, DR and Balmes, JR}, title = {Computed tomography of asbestos-related pulmonary parenchymal and pleural diseases.}, journal = {Clinics in chest medicine}, volume = {12}, number = {1}, pages = {115-131}, pmid = {2009740}, issn = {0272-5231}, mesh = {Asbestosis/*diagnostic imaging ; Humans ; *Image Processing, Computer-Assisted ; Lung/*diagnostic imaging ; Lung Neoplasms/*diagnostic imaging/etiology ; Mesothelioma/*diagnostic imaging/etiology ; Pleural Diseases/diagnostic imaging/etiology ; Pleural Neoplasms/*diagnostic imaging/etiology ; *Tomography, X-Ray Computed/methods ; }, abstract = {Computed tomography has acquired an increasingly central role in the evaluation of asbestos-exposed individuals. The advantages of increased contrast resolution and axial image display have extended our ability to interrogate areas of the pulmonary parenchyma and pleura that are inadequately seen on chest radiographs. The additional information to be gained from CT evaluation must be balanced by the additional expense and time required, particularly in view of the large numbers of asbestos-exposed individuals who will undergo screening over the coming decades. Ideally, imaging strategies that include CT should emphasize those problematic situations in which additional information will serve a differential or diagnostic function, alter the management or habits of the individuals, modify the working environment, or improve our understanding of asbestos-induced diseases. The chest radiograph is the mainstay in the imaging evaluation of asbestos-exposed individuals, providing an inexpensive and rapid appraisal of the presence of both focal and diffuse abnormalities of the pleura and lung parenchyma. Conventional (whole-thorax) CT may be an important adjunct in the following situations: (1) to clarify the presence of pleural thickening, particularly in distinguishing pleural disease from normal extrapleural soft tissues; (2) to stage and determine tumor extent in malignant pleural mesothelioma; (3) to identify optimal sites for biopsy of suspicious pleural changes; and (4) to detect and characterize lung cancers or other focal masses that may be obscured by extensive pleural or parenchymal fibrosis. Limited HRCT studies are roughly competitive in time and cost with four-view radiographic examinations. There is growing evidence that HRCT can detect interstitial disease in advance of conventional clinical or radiographic studies. However, the application of limited HRCT for large-scale screening is controversial. This issue will be resolved as we gain greater understanding of the specificity of HRCT and establish guidelines for standardizing the technique and image interpretation. At present, limited HRCT scans can supplement the evaluation of subjects in whom there is equivocal parenchymal or pleural disease on radiographs or unexplained abnormalities on pulmonary function tests. In individuals with significant pleural disease, HRCT can effectively define the presence and extent of interstitial fibrosis. In individuals with combined cigarette smoking-asbestos exposure in whom symptoms or functional abnormalities are present, HRCT may play a central role in distinguishing emphysematous lung destruction from the peripheral interstitial changes of asbestosis.}, } @article {pmid1848247, year = {1991}, author = {Erzen, C and Eryilmaz, M and Kalyoncu, F and Bilir, N and Sahin, A and Baris, YI}, title = {CT findings in malignant pleural mesothelioma related to nonoccupational exposure to asbestos and fibrous zeolite (erionite).}, journal = {Journal of computer assisted tomography}, volume = {15}, number = {2}, pages = {256-260}, doi = {10.1097/00004728-199103000-00012}, pmid = {1848247}, issn = {0363-8715}, mesh = {Aluminum Silicates/*adverse effects ; Asbestos/*adverse effects ; Environmental Exposure ; Humans ; Mesothelioma/*diagnostic imaging/etiology ; Neoplasm Staging ; Neoplasms, Multiple Primary/diagnostic imaging ; Pleural Effusion/diagnostic imaging ; Pleural Neoplasms/*diagnostic imaging/etiology ; Pulmonary Fibrosis/diagnostic imaging ; *Tomography, X-Ray Computed ; Zeolites ; }, abstract = {Endemic malignant pleural mesothelioma (MPM) in Turkey is related to two mineral fibers, tremolite asbestos and fibrous zeolite (erionite). Thirteen cases of MPM from the Cappadocian area, where the soil is rich in erionite, and 29 cases of MPM, from villages whose occupants have high asbestos exposure, were examined by CT. The CT findings of the two groups of MPM were compared with respect to the configuration of the pleural lesions, stage of disease, fissural involvement, pleural effusion, presence of calcified pleural plaques, and chronic fibrosing pleuritis. In erionite-related MPM the pleural lesions were flat and smooth in 69.1%; in asbestos-related MPM the lesions were nodular in 55.1%. Stage IV disease, calcified pleural plaques, and chronic fibrosing pleuritis were more common in the erionite-related MPM. The rest of the findings were similar in both groups. The early radiological diagnosis of erionite-related MPM may be even more difficult because of the similarity of the pleural lesions to chronic fibrosing pleuritis.}, } @article {pmid1770874, year = {1991}, author = {Gaffuri, E and Maranelli, G}, title = {[The prospects for the appearance of pleural mesothelioma in Italy].}, journal = {La Medicina del lavoro}, volume = {82}, number = {2}, pages = {155-159}, pmid = {1770874}, issn = {0025-7818}, mesh = {Asbestos/adverse effects ; Humans ; Italy/epidemiology ; Mesothelioma/*epidemiology/etiology/mortality ; Pleural Neoplasms/*epidemiology/etiology/mortality ; Sex Factors ; }, abstract = {The mortality data of Italian males and females due to malignant tumour of the pleura, collected over a period of 7 years, from 1976 to 1985, showed a continuous, rectilinear type, increase. The increase in the quantity of asbestos that was processed from 1945 to 1979 was also rectilinear. On the basis of the well known relationship between asbestos and mortality due to mesothelioma, an extremely high correlation coefficient was obtained between quantity of asbestos processed per year and number of deaths due to malignant tumour of the pleura 25 years later. Extrapolating to the year 2000 on the basis of this relationship, it can be foreseen that at that time the deaths due to malignant tumour of the pleura in Italy will be about 1200 per year. It is recommended to apply a correction factor to this figure in order to obtain the number of true cases of mesothelioma, which are probably about 70% of the deaths attributed to tumour of the pleura.}, } @article {pmid1998610, year = {1991}, author = {Browne, K}, title = {Asbestos related malignancy and the Cairns hypothesis.}, journal = {British journal of industrial medicine}, volume = {48}, number = {2}, pages = {73-76}, pmid = {1998610}, issn = {0007-1072}, mesh = {Asbestosis/*etiology ; Cell Division/physiology ; Humans ; Inflammation/*complications ; Lung Neoplasms/*etiology ; Macrophages/physiology ; Mesothelioma/*etiology ; Models, Biological ; Occupational Exposure/adverse effects ; Stem Cells/physiology ; Time Factors ; }, } @article {pmid1998603, year = {1991}, author = {Fatma, N and Jain, AK and Rahman, Q}, title = {Frequency of sister chromatid exchange and chromosomal aberrations in asbestos cement workers.}, journal = {British journal of industrial medicine}, volume = {48}, number = {2}, pages = {103-105}, pmid = {1998603}, issn = {0007-1072}, mesh = {Adult ; Asbestos/*adverse effects ; Asbestosis/epidemiology ; *Chemical Industry ; *Chromosome Aberrations ; Humans ; Incidence ; Occupational Exposure/*adverse effects ; Risk Factors ; *Sister Chromatid Exchange ; Smoking/adverse effects ; }, abstract = {Exposure to asbestos minerals has been associated with a wide variety of adverse health effects including lung cancer, pleural mesothelioma, and cancer of other organs. It was shown previously that asbestos samples collected from a local asbestos factory enhanced sister chromatid exchanges (SCEs) and chromosomal aberrations in vitro using human lymphocytes. In the present study, 22 workers from the same factory and 12 controls were further investigated. Controls were matched for age, sex, and socioeconomic state. The peripheral blood lymphocytes were cultured and harvested at 48 hours for studies of chromosomal aberrations and at 72 hours for SCE frequency determinations. Asbestos workers had a raised mean SCE rate and increased numbers of chromosomal aberrations compared with a control population. Most of the chromosomal aberrations were chromatid gap and break types.}, } @article {pmid1990961, year = {1991}, author = {Rom, WN and Travis, WD and Brody, AR}, title = {Cellular and molecular basis of the asbestos-related diseases.}, journal = {The American review of respiratory disease}, volume = {143}, number = {2}, pages = {408-422}, doi = {10.1164/ajrccm/143.2.408}, pmid = {1990961}, issn = {0003-0805}, mesh = {Animals ; Asbestos/adverse effects/pharmacokinetics ; Asbestosis/*pathology/physiopathology ; Bronchoalveolar Lavage Fluid/pathology ; Fibrosis ; Humans ; Immune System/physiopathology ; Killer Cells, Natural/physiology ; Lung/metabolism/pathology ; Lung Neoplasms/chemically induced ; Mesothelioma/chemically induced/pathology ; Microscopy, Electron ; Microscopy, Electron, Scanning ; Pleura/pathology ; }, abstract = {Asbestosis is an inflammatory and fibrotic process of the alveolar structures mediated, at least in part, by cytokines released by "activated" alveolar macrophages. The process of phagocytosis and "activation" of alveolar macrophages is poorly understood. Are all macrophages activated or only subpopulations? Which cytokines are up-regulated? How does the local milieu modulate profibrotic and antifibrotic mediators? Is protein release accompanied by up-regulation of gene transcription? Is there an ordered sequence of cytokine activity? What roles do neutrophils and lymphocytes play? How can disease progression best be quantified absent further exposure? Answers to these questions are important to direct rational strategies at interdicting the fibrotic process. The question of cancer and asbestos is more vexing. The processes of inflammation, fibrosis, and carcinogenesis appear to be closely intertwined. For example, proto-oncogenes such as c-sis (PDGF B-chain) are up-regulated in activated alveolar macrophages from fibrotic lungs; these and possibly others may play an important role in asbestos carcinogenesis. Second, asbestos can transfect DNA into cells. Furthermore, DNA can adhere to asbestos fibers, and these fibers are capable of direct transmigration into cells. The questions of the mechanisms of cigarette smoke cocarcinogenicity and latency remain. Lastly, if the bronchial epithelium is highly metaplastic throughout from cigarette smoking, what triggers a single (or several) nidus of cells to transform into carcinoma? Malignant mesothelioma poses the most challenging questions because of association with brief asbestos exposure by history. Mesothelial cells are susceptible to minute environmental manipulations, and changes occur after exposure to all fiber types. Yet epidemiologic studies point toward long amphiboles as having greater mesothelioma risk. To test this hypothesis, experimental data must be generated differentiating tumorigenesis risk from short, chrysotile fibers that can migrate to the parietal pleura from the associations of long amphiboles persisting in lung tissue. Despite the future decreasing numbers of clinical cases of asbestos-related disease, solving the important mechanistic questions remaining will contribute significantly to our understanding of fibrosis and cancer.}, } @article {pmid1703129, year = {1991}, author = {Manning, LS and Whitaker, D and Murch, AR and Garlepp, MJ and Davis, MR and Musk, AW and Robinson, BW}, title = {Establishment and characterization of five human malignant mesothelioma cell lines derived from pleural effusions.}, journal = {International journal of cancer}, volume = {47}, number = {2}, pages = {285-290}, doi = {10.1002/ijc.2910470219}, pmid = {1703129}, issn = {0020-7136}, mesh = {Adult ; Asbestos/adverse effects ; Carcinoembryonic Antigen/analysis ; Cell Division ; Cytoplasm/pathology ; Glycogen/metabolism ; Humans ; Karyotyping ; Keratins/analysis ; Male ; Membrane Glycoproteins/analysis ; Mesothelioma/chemistry/genetics/*pathology ; Microscopy, Electron ; Middle Aged ; Mucin-1 ; Pleural Effusion/*pathology ; Polymorphism, Restriction Fragment Length ; *Tumor Cells, Cultured ; Vacuoles/pathology ; }, abstract = {Malignant mesothelioma (MM) is an aggressive tumour of the serosal cavities which is associated with exposure to asbestos. Studies of this tumour have been limited by a paucity of well-characterized human MM cell lines. In this study, 5 human MM cell lines were established from pleural effusions of patients with this malignancy. All 5 patients were males with known crocidolite asbestos exposure, who had received no treatment for their disease and in whom the diagnosis was confirmed by cytology, histology and electron microscopy (EM). These lines have been in culture from 11 to 25 months, and all of them for more than 18 passages. The appearance of the cells in culture was extremely varied; in 3 of the lines they were spindle-shaped with few vacuoles (JU77, LO68 and ONE58); in 1 line they had a thick, stellate shape with vacuoles (NO36) and in 1 they were very pleomorphic in both shape and size with irregular membranes and numerous vacuoles [DeH128 (M)]. Upon reaching confluence, cells in 3 of the 5 lines assumed the cobblestone-like pattern characteristic of epithelial-type cells, whereas in the other 2 (LO68 and ONE58) they remained spindle-shaped. All 5 lines demonstrated a loss of contact inhibition (i.e., piling) at confluence. Minimum doubling times varied significantly from 18 hr (JU77) to more than 30 hr [DeH128 (M)]. Cytological examination showed characteristic mesothelial/mesothelioma morphology, and epithelial membrane antigen (EMA) and cytokeratin were demonstrated in cells from all 5 lines. These cells lacked CEA and epithelial mucin. The presence of cell junctions, glycogen and numerous long, thin, branching microvilli was readily demonstrable by EM. All lines had abnormal karyotypes, with the modal chromosome number varying from 40 to 80. Variable chromosome numbers, numerous structural rearrangements and unrecognizable marker chromosomes were readily observed; however, the only consistent change seen was del 6q21 in 4 of the 5 lines. The establishment of these 5 cultured human MM cell lines now provides an opportunity for comparative study of several aspects of the biology of MM in vitro as well as screening new treatment modalities.}, } @article {pmid1996167, year = {1991}, author = {Meijers, JM and Planteydt, HT and Slangen, JJ and Swaen, GM and van Vliet, C and Sturmans, F}, title = {[Course and distribution of mortality of pleural mesothelioma in The Netherlands, 1970-1987].}, journal = {Nederlands tijdschrift voor geneeskunde}, volume = {135}, number = {3}, pages = {93-98}, pmid = {1996167}, issn = {0028-2162}, mesh = {Adult ; Aged ; Demography ; Female ; Humans ; Male ; Mesothelioma/*epidemiology/mortality ; Middle Aged ; Netherlands/epidemiology ; Occupations ; Pleural Neoplasms/*epidemiology/mortality ; Prognosis ; Regression Analysis ; }, abstract = {In this article the sex- and age-specific trends and geographical distribution of asbestos related pleural mesothelioma mortality in the Netherlands between 1970 and 1987 are investigated. For men total mortality increased from 10.8 per million during 1970-1978 to 20.9 per million during 1979-1987. The highest mortality occurred with 147.7 per million in 1987 in the age group between 65 and 74 years. Mortality rates for the age group between 55 and 64 years amounted to 96.5 per million in 1987. The geographical distribution over the country showed a strong concentration of male mesothelioma cases in the regions with many harbours, shipyards and heavy industries round Amsterdam, IJmuiden, Rotterdam, Dordrecht and Walcheren. Using linear regression techniques, it was calculated that several thousands new mesothelioma cases will occur in the Netherlands during the next two decades. A significant decrease in mesothelioma mortality can not be expected before 2010.}, } @article {pmid2053581, year = {1991}, author = {Varouchakis, G and Velonakis, EG and Amfilochiou, S and Trichopoulos, D}, title = {Asbestos in strange places: two case reports of mesothelioma among merchant seamen.}, journal = {American journal of industrial medicine}, volume = {19}, number = {5}, pages = {673-676}, doi = {10.1002/ajim.4700190511}, pmid = {2053581}, issn = {0271-3586}, mesh = {Aged ; Asbestos/*adverse effects ; Humans ; Male ; Mesothelioma/*etiology ; Naval Medicine ; Occupational Diseases/*etiology ; }, } @article {pmid2031775, year = {1991}, author = {de Cuenca Morón, B and Moreno Sánchez, D and Belda Serna, A and Solís Herruzo, JA}, title = {[Diffuse peritoneal mesothelioma. Apropos 2 cases and a review of the literature].}, journal = {Revista espanola de enfermedades digestivas}, volume = {79}, number = {1}, pages = {55-59}, pmid = {2031775}, issn = {1130-0108}, mesh = {Aged ; Biopsy ; Female ; Humans ; Laparotomy ; Male ; Mesothelioma/*diagnosis/pathology ; Middle Aged ; Peritoneal Neoplasms/*diagnosis/pathology ; Peritoneum/pathology ; }, abstract = {Two cases of diffuse peritoneal mesothelioma are reported. They were not associated with asbestos exposure and they presented as fever of unknown origin and ascitic syndrome, respectively. The literature is reviewed.}, } @article {pmid1993160, year = {1991}, author = {Tuomi, T and Huuskonen, MS and Tammilehto, L and Vanhala, E and Virtamo, M}, title = {Occupational exposure to asbestos as evaluated from work histories and analysis of lung tissues from patients with mesothelioma.}, journal = {British journal of industrial medicine}, volume = {48}, number = {1}, pages = {48-52}, pmid = {1993160}, issn = {0007-1072}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Employment/statistics & numerical data ; Female ; Humans ; Lung/*pathology ; Lung Neoplasms/*etiology/pathology ; Male ; Mesothelioma/*etiology/pathology ; Middle Aged ; Occupational Diseases/*etiology/pathology ; Occupational Exposure/*adverse effects/statistics & numerical data ; }, abstract = {The past occupational exposure to asbestos of 23 patients with mesothelioma (21 men and two women) has been evaluated by a personal interview of their work history and by determination of the fibre burden in their lung tissue with scanning electron microscopy (SEM) and x ray microanalysis. According to the work history, nine patients (39%) had definitely been or probably been exposed to asbestos, six patients (26%) had had possible exposures, and eight patients (35%) unlikely or unknown exposure to asbestos. The two female patients were in the unknown exposure category. The fibre concentrations in the patients' lung tissue ranged from less than 0.1 million to 370 million fibres (f) per g dry tissue. Concentrations of over one million f per g dry tissue were found in 15 patients (65%). The lung fibre concentrations of all nine male office workers analysed for reference were less than one million f per g dry tissue. Seventy eight per cent of the patients with mesothelioma had at least possible exposure according to their history of work or concentrations of more than one million f per g dry tissue.}, } @article {pmid1951372, year = {1991}, author = {Hilt, B and Andersen, A and Rosenberg, J and Langård, S}, title = {Cancer incidence among asbestos-exposed chemical industry workers: an extended observation period.}, journal = {American journal of industrial medicine}, volume = {20}, number = {2}, pages = {261-264}, doi = {10.1002/ajim.4700200211}, pmid = {1951372}, issn = {0271-3586}, mesh = {Asbestos/*adverse effects ; *Chemical Industry ; Cohort Studies ; Environmental Exposure/*adverse effects ; Follow-Up Studies ; Humans ; Lung Neoplasms/epidemiology/etiology ; Neoplasms/*epidemiology/etiology ; Norway/epidemiology ; Registries ; }, abstract = {A previous study on the incidence of cancer in a cohort of 286 asbestos-exposed electrochemical industry workers observed from 1953 through 1980 has been extended with another 8 years of follow-up. The incidence of cancer was derived from the Cancer Registry of Norway, and the expected figures were calculated by a life table method. During the extended follow-up period from 1981 through 1988, among the cohort members there were 12 new cancer cases versus 14.2 expected (SIR 85, 95% CI 44-158). In a lightly exposed sub-cohort, the extended follow-up revealed 4 cases of lung cancer or pleural mesothelioma (ICD, 7th revision 162-163) versus 1.6 cases expected (SIR 256, 95% CI71-654). In a heavily exposed sub-cohort, the corresponding figures were 3 and 0.5 (SIR 588, 95% CI 118-1,725).}, } @article {pmid1928116, year = {1991}, author = {Newhouse, ML}, title = {Mesothelioma in the London area.}, journal = {American journal of industrial medicine}, volume = {20}, number = {3}, pages = {411-413}, doi = {10.1002/ajim.4700200313}, pmid = {1928116}, issn = {0271-3586}, mesh = {Asbestos/adverse effects ; Environmental Exposure/adverse effects ; History, 20th Century ; Humans ; London ; Mesothelioma/*history ; Occupational Diseases/*history ; }, } @article {pmid1928113, year = {1991}, author = {Cicioni, C and London, SJ and Garabrant, DH and Bernstein, L and Phillips, K and Peters, JM}, title = {Occupational asbestos exposure and mesothelioma risk in Los Angeles County: application of an occupational hazard survey job-exposure matrix.}, journal = {American journal of industrial medicine}, volume = {20}, number = {3}, pages = {371-379}, doi = {10.1002/ajim.4700200309}, pmid = {1928113}, issn = {0271-3586}, support = {CA 01291/CA/NCI NIH HHS/United States ; CA17054/CA/NCI NIH HHS/United States ; IT15 OH07214/OH/NIOSH CDC HHS/United States ; }, mesh = {Adolescent ; Adult ; Asbestos/*adverse effects ; Case-Control Studies ; Humans ; Los Angeles ; Lung Neoplasms/etiology ; Male ; Mesothelioma/*etiology ; Middle Aged ; National Institute for Occupational Safety and Health, U.S. ; Occupational Diseases/*etiology ; Occupational Exposure/*adverse effects ; Odds Ratio ; Population Surveillance ; Registries ; Risk Factors ; United States ; }, abstract = {We evaluated the newly available National Institute for Occupational Safety and Health (NIOSH) National Occupational Hazard Survey (NOHS) job exposure matrix (JEM) by considering mesothelioma risk from asbestos exposure. We applied this system (NOHS-JEM) to the Los Angeles County Cancer Surveillance Program (CSP) to see how many cancer cases could be assigned asbestos exposure and how asbestos exposure affected mesothelioma risk. Using the same CSP data, our "experts" classified asbestos exposure simply by occupation and industry. Both exposure classifications were divided into low and high; the NOHS-JEM by the number of exposed people per couplet, and ours by judgements of intensity. Odds ratios (OR) for mesothelioma risk for low and high asbestos exposure for the NOHS-JEM were 2.0 (95% C.I. 1.2-3.4) and 2.5 (95% C.I. 1.2-4.8). For ours, corresponding risks were 1.6 (95% C.I. 1.1-2.4) and 6.3 (95% C.I. 2.5-15.1). Our system was able to assign more cases to couplets then the NOHS-JEM (35,895 to 22,369). Three limitations of the NOHS-JEM were that many occupation-industry couplets were not classified at all, many couplets associated with past asbestos exposure (before the 1972-1974 NOHS survey) were not classified as asbestos exposure, and no assessment of intensity was made. These limitations may apply to other exposures and should be carefully considered before the NOHS-JEM is applied to other case-control studies.}, } @article {pmid1921345, year = {1991}, author = {Ribak, J and Lilis, R and Suzuki, Y and Penner, L and Selikoff, IJ}, title = {Death certificate categorization of malignant pleural and peritoneal mesothelioma in a cohort of asbestos insulation workers.}, journal = {The Journal of the Society of Occupational Medicine}, volume = {41}, number = {3}, pages = {137-139}, doi = {10.1093/occmed/41.3.137}, pmid = {1921345}, issn = {0301-0023}, mesh = {Asbestos/*adverse effects ; Cohort Studies ; *Death Certificates ; Humans ; Mesothelioma/*diagnosis ; Occupational Diseases/*diagnosis/etiology ; Peritoneal Neoplasms/*diagnosis ; Pleural Neoplasms/*diagnosis ; }, abstract = {Accuracy of diagnosis of malignant mesothelioma (pleural and peritoneal) was studied in a cohort of asbestos insulation workers in the United States and Canada. Initial clinical diagnosis, clinical diagnosis at death and death certificate diagnosis were compared with the diagnosis of malignant mesothelioma ascertained by full data review at the Division of Environmental and Occupational Medicine, Mount Sinai Medical Center, New York ('best evidence'). In both groups the death certificate diagnosis was somewhat less frequently accurate than clinical diagnosis at death. Knowledge of the patients' occupational history by the attending physician and its relation to accuracy of diagnosis of malignant mesothelioma is considered.}, } @article {pmid1885300, year = {1991}, author = {Flechsig, R}, title = {Peritoneal mesothelioma--how a good occupational case history can best be used.}, journal = {Industrial health}, volume = {29}, number = {2}, pages = {73-76}, doi = {10.2486/indhealth.29.73}, pmid = {1885300}, issn = {0019-8366}, mesh = {Adolescent ; Adult ; Asbestos/adverse effects ; Child ; Female ; Humans ; Male ; Medical History Taking/*methods ; Mesothelioma/*diagnosis ; Middle Aged ; Occupational Diseases/*diagnosis ; Peritoneal Neoplasms/*diagnosis ; }, } @article {pmid1882849, year = {1991}, author = {Suzuki, Y and Kohyama, N}, title = {Translocation of inhaled asbestos fibers from the lung to other tissues.}, journal = {American journal of industrial medicine}, volume = {19}, number = {6}, pages = {701-704}, doi = {10.1002/ajim.4700190603}, pmid = {1882849}, issn = {0271-3586}, mesh = {Adolescent ; Adult ; Asbestos/*analysis ; Asbestosis/*metabolism ; *Foreign-Body Migration ; Humans ; Lung/chemistry ; Male ; Mesothelioma/*metabolism ; Peritoneal Neoplasms/*metabolism ; Peritoneum/pathology ; Pleura/chemistry ; Pleural Neoplasms/*metabolism ; }, abstract = {To investigate translocation of asbestos fibers, tissue samples from 13 North American insulators were examined, using electron microscopy. Of the two major types of asbestos, chrysotile and amosite, chrysotile was found to be much more active in the translocation than amosite, being the fiber mainly detected in mesotheliomas and hyaline plaques.}, } @article {pmid1853357, year = {1991}, author = {Sluis-Cremer, GK}, title = {Asbestos disease at low exposure after long residence time in amphibole miners.}, journal = {Toxicology and industrial health}, volume = {7}, number = {1-2}, pages = {89-95}, doi = {10.1177/074823379100700106}, pmid = {1853357}, issn = {0748-2337}, mesh = {Asbestos/*adverse effects ; Asbestosis/epidemiology/etiology ; Autopsy ; Bronchial Neoplasms/epidemiology/etiology ; Humans ; Male ; Mesothelioma/epidemiology/etiology ; *Mining ; Occupational Diseases/epidemiology/*etiology ; Retrospective Studies ; Time Factors ; }, abstract = {Short reports of several studies carried out in South Africa which have a bearing on the health effects of low exposures to asbestos are presented. It is stressed that the findings refer solely to amphibole asbestos. Average fiber exposure of 1 or less or a cumulative exposure of less than 2-5 fibers/ml years is associated with the development of asbestosis increasing in frequency with residence time.}, } @article {pmid1853354, year = {1991}, author = {Mehlman, MA}, title = {Dangerous and cancer-causing properties of products and chemicals in the oil refining and petrochemical industry: Part V--Asbestos-caused cancers and exposure of workers in the oil refining industry.}, journal = {Toxicology and industrial health}, volume = {7}, number = {1-2}, pages = {53-71}, doi = {10.1177/074823379100700103}, pmid = {1853354}, issn = {0748-2337}, mesh = {Asbestos/*adverse effects/history ; *Chemical Industry ; History, 19th Century ; History, 20th Century ; History, Ancient ; Humans ; Neoplasms/*etiology ; Occupational Diseases/*etiology/history ; *Petroleum ; Risk Factors ; United States/epidemiology ; }, abstract = {In the oil refining and petrochemical industries exposure to cancer-causing asbestos particles, especially during equipment repair and maintenance, is very high. Up to 90% of workers in the oil refining industry had direct and/or indirect contact with asbestos, and more than half of this contact occurred without the use of any kind of precaution, thus these workers are in high risk of developing lung cancer and mesothelioma, both fatal diseases. The hazards include: inadequate health and safety training for both company personnel and workers, failure to inform about the dangers and diseases (cancers) resulting from exposure to asbestos; excessive use of large numbers of untrained and uninformed contract workers; lack of use of protective equipment; and archaeological approaches and responses to repairing asbestos breaks and replacement of asbestos in oil refining facilities. For a better understanding of practices and policies in the oil refining industry, refer to Rachel Scott's Muscle and Blood, in particular the chapter "Oil" (E.P. Dutton, New York, 1974), as well as to an editorial which appeared in the Oil and Gas Journal, April, 1968.}, } @article {pmid1853352, year = {1991}, author = {Maltoni, C and Pinto, C and Mobiglia, A}, title = {Mesotheliomas following exposure to asbestos used in railroads: the Italian cases.}, journal = {Toxicology and industrial health}, volume = {7}, number = {1-2}, pages = {1-45}, doi = {10.1177/074823379100700101}, pmid = {1853352}, issn = {0748-2337}, mesh = {Adult ; Asbestos/*adverse effects ; Humans ; Italy/epidemiology ; Mesothelioma/epidemiology/*etiology ; Occupational Diseases/epidemiology/*etiology ; *Railroads ; Retrospective Studies ; Risk Factors ; }, abstract = {The available knowledge on the oncogenic risks of asbestos, the data on the uses of asbestos in railroads, with particular regard to the Italian State Railroads (Ferrovie dello Stato = FS), and the groups at risk due to the exposure to asbestos used in railroads were briefly reviewed. The available data on the pathological effects of such exposure, and in particular on the onset of mesotheliomas among machinists and other railroad workers, were also summarized. Eighty-five cases of mesothelioma (80 pleural, 4 peritoneal, and 1 pericardial), related to the exposure to asbestos used in railroads, observed in various Italian regions, were then reported. Twenty-eight of these cases (among which 27 reported in the Emilia-Romagna Region) were submitted to a detailed study at the Bologna Institute of Oncology. Fifty cases of mesothelioma occurred among FS workers, in particular machinists; 30 cases occurred among machinists of rolling-stock workshops not belonging to the FS; 3 cases occurred among travelling workers of rolling-stock not belonging to the FS; and 2 cases were found in family members (a daughter and a wife) of FS workers. This series of cases, together with similar data from the literature, proves the existence of an actually health risk due to asbestos used in railroads, and indicates its gravity. On the basis of the available data, the following steps are considered necessary: the adoption of preventive measures, the performance of medical oncological surveillance, the promotion of systematic epidemiological investigations, and, finally, more emphasis on basic research, aimed at generating information on the biological events taking place during the incubation period of the tumors, to be used for reducing the effect of exposure, and therefore for contrasting the onset of the disease in those who, having been exposed, although healthy, are potentially at high risk.}, } @article {pmid1852099, year = {1991}, author = {Woitowitz, HJ and Rödelsperger, K}, title = {Chrysotile asbestos and mesothelioma.}, journal = {American journal of industrial medicine}, volume = {19}, number = {4}, pages = {551-553}, doi = {10.1002/ajim.4700190413}, pmid = {1852099}, issn = {0271-3586}, mesh = {Asbestos/*adverse effects ; Asbestos, Serpentine ; Humans ; Incidence ; Lung Neoplasms/epidemiology/*etiology ; Mesothelioma/epidemiology/*etiology ; Occupational Diseases/epidemiology/*etiology ; }, } @article {pmid1847001, year = {1991}, author = {Cullen, MR and Baloyi, RS}, title = {Chrysotile asbestos and health in Zimbabwe: I. Analysis of miners and millers compensated for asbestos-related diseases since independence (1980).}, journal = {American journal of industrial medicine}, volume = {19}, number = {2}, pages = {161-169}, doi = {10.1002/ajim.4700190204}, pmid = {1847001}, issn = {0271-3586}, mesh = {Asbestos ; Asbestos, Serpentine ; Asbestosis/*epidemiology ; Humans ; Male ; *Mining ; Occupational Exposure ; Risk Factors ; Workers' Compensation ; Zimbabwe/epidemiology ; }, abstract = {Data on the health effects caused by locally mined chrysotile asbestos in Zimbabwe have been very limited. The prevailing local view has been that risk is minimal. In this report we critically reassess the cases of 51 individuals with asbestos exposure who have been compensated by the Central Pneumoconiosis Bureau since independence in 1980. Results demonstrate that the major health risks of exposure reported elsewhere--morbid asbestosis, nonmalignant pleural disease, malignant mesothelioma, and lung cancer--all occur in Zimbabwe, at least among workers in the asbestos mines and mills. It is concluded that further investigation and control measures in the industry are warranted.}, } @article {pmid1846329, year = {1991}, author = {Manning, LS and Davis, MR and Robinson, BW}, title = {Asbestos fibres inhibit the in vitro activity of lymphokine-activated killer (LAK) cells from healthy individuals and patients with malignant mesothelioma.}, journal = {Clinical and experimental immunology}, volume = {83}, number = {1}, pages = {85-91}, pmid = {1846329}, issn = {0009-9104}, mesh = {Asbestos/*toxicity ; Asbestos, Amosite ; Asbestos, Crocidolite ; Asbestos, Serpentine ; Cell Survival/drug effects ; Cytotoxicity Tests, Immunologic ; Female ; Humans ; In Vitro Techniques ; Interleukin-2/immunology ; Killer Cells, Lymphokine-Activated/*drug effects ; Killer Cells, Natural/drug effects ; Male ; Mesothelioma/*immunology ; Tumor Cells, Cultured ; }, abstract = {Asbestos exposure is associated with an increased incidence of several malignancies, including malignant mesothelioma (MM). This study evaluates the relationship between asbestos exposure and the in vitro generation and function of LAK cells, an immune effector cell population with powerful lytic activity against MM cells. Both serpentine (chrysotile) and amphibole (amosite and crocidolite) forms of asbestos fibres suppress LAK cell generation, viability (by 5-11%, P less than 0.02) and cell recovery (by 13-15%, P less than 0.02). However, the LAK cells generated in the presence of the amphiboles were as effective as unexposed cells in lysing both standard tumour cell targets (K562, 56.4% lysis versus 61.5%, respectively, P greater than 0.5; NS; Daudi, 60.5% lysis versus 64.5% P greater than 0.5; NS), and MM tumour cell targets (mean of three MM cell lines 48.3% versus 46.3%, P greater than 0.5; NS), whereas the function of LAK cells generated in the presence of chrysotile was significantly reduced against three out of the five tumour cell targets tested (P less than 0.03). In the presence of asbestos fibres, LAK cell function was reduced against all five tumour cell targets (P less than 0.01), irrespective of whether the cell donors were healthy individuals or patients with MM. NK cell activity was also suppressed (P less than 0.01). The serpentine form of asbestos, chrysotile, was significantly more suppressive of both effector cell functions than either of the amphiboles (P less than 0.01). These findings suggest that asbestos exposure may suppress the function and in some instances the generation of immune effector cell mechanisms, thereby increasing the risk of disease and malignancy.}, } @article {pmid1843649, year = {1991}, author = {Szturmowicz, M and Vertun-Baranowska, B and Rowińska-Zakrzewska, E and Szymańska, D}, title = {[Incidence of pleural mesotheliomas in Poland (preliminary report)].}, journal = {Pneumonologia i alergologia polska}, volume = {59}, number = {9-10}, pages = {55-61}, pmid = {1843649}, issn = {0867-7077}, mesh = {Adolescent ; Adult ; Aged ; Female ; Humans ; Incidence ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Pleural Neoplasms/*epidemiology ; Poland/epidemiology ; }, abstract = {Mesothelioma is a rare malignancy, difficult to diagnose and rarely found in a population not exposed to asbestos. In the immediate past incidence rates of this disease have increased due to extensive use of this mineral in the industry of the 1950's. The aim of this study was to assess the incidence of mesotheliomas basing on results of a questionnaire posted in 1987 to all pneumonology clinics, oncological departments in Poland, and data from the Central Oncological Register from the years 1970-1985. Incidence of this malignant disease was 1-2 cases per 1,000,000 of general population during the years 1970-1985 and did not rise in 1986. Regional differences were observed, in some areas the incidence rate was 5-6 per 1,000,000. Data from the Occupational Medicine Institute disclosed in these regions more extensive industrial use of this mineral. The authors have also concluded that "at-life" diagnosis of mesothelioma rises, mainly due to the use of open pleural biopsy.}, } @article {pmid1826191, year = {1991}, author = {Morgan, RW}, title = {Re: Meta-analysis of asbestos and gastrointestinal cancer.}, journal = {American journal of industrial medicine}, volume = {19}, number = {3}, pages = {407-411}, doi = {10.1002/ajim.4700190315}, pmid = {1826191}, issn = {0271-3586}, mesh = {Asbestos/*adverse effects ; Diagnosis, Differential ; Gastrointestinal Neoplasms/*epidemiology ; Humans ; Incidence ; Lung Neoplasms/diagnosis/etiology ; Mesothelioma/diagnosis/etiology ; Meta-Analysis as Topic ; }, } @article {pmid1808450, year = {1991}, author = {Szeszenia-Dabrowska, N and Wilczyńska, U and Kaczmarek, T and Szymczak, W}, title = {[Evaluation of the cancer risk among men exposed to occupational asbestos dust based on cohort studies].}, journal = {Medycyna pracy}, volume = {42}, number = {6}, pages = {419-419}, pmid = {1808450}, issn = {0465-5893}, mesh = {Air Pollutants, Occupational/*adverse effects ; Asbestos/administration & dosage/*adverse effects ; Asbestosis/*complications/epidemiology/mortality ; Cohort Studies ; Digestive System Neoplasms/epidemiology/*etiology/mortality ; Dust/adverse effects ; Humans ; Male ; Occupational Diseases/epidemiology/*etiology/mortality ; Occupational Exposure ; Poland/epidemiology ; Respiratory Tract Neoplasms/epidemiology/*etiology/mortality ; Risk Factors ; Time Factors ; }, abstract = {The results of the study of a cohort of 2403 men occupationally exposed to chrysotile asbestos dust during the manufacture of various asbestos products have been reported. The study covered the period 1945-1985. Cohort availability was 91%. Risk estimates were based on SMR and SRR calculated by the man-year method. The general Polish male population served for the reference. The analysis was performed for sub-cohorts selected according to the period of employment in the plant, taking into account the dust dose and the age at the moment of the beginning of employment under exposed conditions. A significantly increased risk of pulmonary carcinoma (SMR: 238.0-211.0) and of gastric carcinoma (SMR: 197.9-238.5) was found in men exposed to high doses of the asbestos dust (above 50 mg/m3 x years). No statistically significant increases in the mortality rates either from cancer in general or from the cancer varieties specified above were detected in men exposed to low doses of dust. One case of death from pleural mesothelioma was reported.}, } @article {pmid1799843, year = {1991}, author = {Grahl, KO and Kunzelmann, F}, title = {[Asbestosis in the thoracic roentgen image].}, journal = {Bildgebung = Imaging}, volume = {58 Suppl 1}, number = {}, pages = {30-32}, pmid = {1799843}, issn = {1012-5655}, mesh = {Asbestosis/*diagnostic imaging ; Calcinosis/diagnostic imaging ; Carcinoma, Bronchogenic/diagnostic imaging ; Humans ; Lung Neoplasms/diagnostic imaging ; Mesothelioma/diagnostic imaging ; Pleura/diagnostic imaging ; Pleural Neoplasms/diagnostic imaging ; Radiography ; }, abstract = {Asbestos is a silicate fiber that may cause asbestosis 20-30 years after exposition. Asbestosis is characterized by pulmonary fibrosis, thickening of the pleura and calcified pleuraplaques. In addition, asbestosis may lead to bronchial carcinoma or mesothelioma. As patients are rarely referred to rule out asbestosis, and chest films are obtained for other clinical questions, it is important for the radiologist to recognize the typical plain film findings. These typical signs are illustrated in the following manuscript.}, } @article {pmid1793113, year = {1991}, author = {Huncharek, M}, title = {Occult asbestos exposure.}, journal = {American journal of industrial medicine}, volume = {20}, number = {5}, pages = {713-714}, doi = {10.1002/ajim.4700200515}, pmid = {1793113}, issn = {0271-3586}, mesh = {Air Pollutants, Occupational/adverse effects/analysis ; Asbestos/*adverse effects/analysis ; Humans ; Male ; Mesothelioma/*chemically induced ; Middle Aged ; Occupational Diseases/*chemically induced ; Pleural Neoplasms/*chemically induced ; Risk Factors ; *Teaching ; }, } @article {pmid1793109, year = {1991}, author = {Enterline, PE}, title = {Changing attitudes and opinions regarding asbestos and cancer 1934-1965.}, journal = {American journal of industrial medicine}, volume = {20}, number = {5}, pages = {685-700}, doi = {10.1002/ajim.4700200511}, pmid = {1793109}, issn = {0271-3586}, mesh = {Asbestos/*adverse effects ; Asbestosis/complications/etiology/history ; *Health Knowledge, Attitudes, Practice ; History, 20th Century ; Humans ; Lung Neoplasms/epidemiology/etiology/*history ; Mesothelioma/epidemiology/etiology/*history ; Occupational Diseases/epidemiology/etiology/*history ; Publishing ; Risk Factors ; United States ; }, abstract = {Literature published in the years 1934-1965 was reviewed to determine attitudes and opinions of scientists as to whether asbestos is a cause of cancer. In Germany, the issue was decided in 1943 when the government decreed that lung cancer, when associated with asbestosis (of any degree), was an occupational disease. In the United States, however, there was no consensus on the issue until 1964. Opinions of scientists over a 22 year period are shown and the contributions of various cultural, social, economic and political factors to these opinions are discussed. A lack of experimental and epidemiological evidence played a major role in delaying a consensus. Other important factors included a rejection of science conducted outside of the U.S. during this period, particularly a rejection of German scientific thought during and after WWII, and a rejection of clinical evidence in favor of epidemiological investigations. Individual writers rarely changed their minds on the subject of asbestos as a cause of cancer.}, } @article {pmid1793106, year = {1991}, author = {Leigh, J and Corvalán, CF and Grimwood, A and Berry, G and Ferguson, DA and Thompson, R}, title = {The incidence of malignant mesothelioma in Australia 1982-1988.}, journal = {American journal of industrial medicine}, volume = {20}, number = {5}, pages = {643-655}, doi = {10.1002/ajim.4700200507}, pmid = {1793106}, issn = {0271-3586}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Australia/epidemiology ; Female ; Humans ; Incidence ; Male ; Mesothelioma/chemically induced/*epidemiology ; Middle Aged ; Occupational Diseases/chemically induced/*epidemiology ; Peritoneal Neoplasms/chemically induced/*epidemiology ; Pleural Neoplasms/chemically induced/*epidemiology ; }, abstract = {From 1980 to 1985, the Australian Mesothelioma Surveillance Program, and since 1986, the Australian Mesothelioma Register, have been collecting data on all cases of malignant mesothelioma that could be ascertained in Australia. Incidence rates were calculated on 854 Program and 696 Register cases (total 1271) diagnosed in Australia between January 1, 1982 and December 31, 1988. Australia has one of the highest national rates of mesothelioma in the world (15.8 cases per million of population aged 20 years and older), and the rate is rising. The rate is far higher in males (28.3) than females (3.3). The Western Australian rate (28.9) is the highest among the states, as may be expected because of the crocidolite mine at Wittenoom; however, the largest numbers of cases occur in the more populous and industrial New South Wales. The high incidence rate, its expected continuing increase, and absence of a history of exposure to asbestos in approximately 28% of cases, demand consideration of potential environmental factors other than asbestos in the causation of this tumor, as well as continued surveillance.}, } @article {pmid1793104, year = {1991}, author = {Selikoff, IJ and Seidman, H}, title = {Evaluation of selection bias in a cross-sectional survey.}, journal = {American journal of industrial medicine}, volume = {20}, number = {5}, pages = {615-627}, doi = {10.1002/ajim.4700200505}, pmid = {1793104}, issn = {0271-3586}, mesh = {Asbestos/adverse effects ; Asbestosis/*epidemiology/etiology/mortality ; *Cohort Studies ; *Cross-Sectional Studies ; Health Status ; Humans ; Lung Diseases/chemically induced/*epidemiology/mortality ; Male ; Occupational Diseases/*epidemiology/mortality ; Prospective Studies ; *Selection Bias ; United States/epidemiology ; }, abstract = {Selection bias is inherent in all occupational cohorts. Selection bias at entry has long been known and is commonly referred to as a "healthy worker effect." Less well appreciated is selection during the life of a cohort resulting from life-style factors (e.g., cigarette smoking); aging with accompanying chronic diseases, economic and demographic circumstances; and diseases that might result from exposures suffered by the cohort being studied, that influence whether individuals remain in a trade. These factors weigh differently at different times. Thus, at any point in time, "surviving" members of a cohort reflect an amalgam of selection factors. When such groups are studied in cross-sectional surveys there can be uncertainty whether clinical, radiological and physiological findings are necessarily representative for the trade or occupation as a whole. We analyzed the results of a large clinical field survey of long-term asbestos insulation workers to investigate whether the non-participants differed substantially from those who were examined. Five thousand three hundred and fifty-five (5,355) men, of an initial cohort of 17,800 established January 1, 1967, had reached 30 or more years from onset of their work by July 1, 1981. All were invited to come for examination. Two thousand and seventy-seven (2,077) came, and 3,278 did not. We questioned a sample of 1,393 non-responders to see why they failed to appear. The answers did not give evidence of significant health-related selection influence. Sickness only infrequently kept them away. We then followed both groups--those examined and those not examined--to the end of 1987 for their mortality experience. There was no great difference. The non-responders had somewhat fewer deaths overall and proportionately fewer of asbestos-associated cancers, such as mesothelioma and lung cancer. The results indicated that, in this cohort, there did not seem to be health-related selection bias that determined whether or not cohort members responded to invitations for examinations.}, } @article {pmid1755586, year = {1991}, author = {Vetrugno, T and Comba, P and Savelli, D and Belli, S and Magnani, C}, title = {[Epidemiologic surveillance of pleural mesothelioma in Italy].}, journal = {Annali dell'Istituto superiore di sanita}, volume = {27}, number = {2}, pages = {319-324}, pmid = {1755586}, issn = {0021-2571}, mesh = {Asbestos/adverse effects ; Australia/epidemiology ; Environmental Exposure ; Europe/epidemiology ; Humans ; Incidence ; Italy/epidemiology ; Mesothelioma/*epidemiology/etiology/mortality ; Occupational Diseases/epidemiology/etiology/mortality ; Occupational Exposure ; Pleural Neoplasms/*epidemiology/etiology/mortality ; *Population Surveillance ; Quebec/epidemiology ; Registries ; South Africa/epidemiology ; }, abstract = {A collaborative study has been performed in order to detect cases of pleural mesothelioma diagnosed or treated in Italy in the years 1984-88. Cases have been notified to ISS by 88 centres (clinics of thoracic surgery and respiratory diseases, oncologic centres, institutes of pathology), active in 14 Italian regions. Altogether, 575 cases (415 males and 160 females) have been included in the study. Information on occupation and/or on non occupational exposure to asbestos was available for 65% of the subjects, and the occurrence of definite or possible exposure to asbestos was estimated for 58% of them.}, } @article {pmid1745856, year = {1991}, author = {Huncharek, M and Muscat, J}, title = {Metastatic laryngeal carcinoma mimicking pleural mesothelioma.}, journal = {Respiration; international review of thoracic diseases}, volume = {58}, number = {3-4}, pages = {204-206}, doi = {10.1159/000195927}, pmid = {1745856}, issn = {0025-7931}, mesh = {Aged ; Asbestos/adverse effects ; Carcinoma, Squamous Cell/diagnosis/*secondary ; Diagnosis, Differential ; Humans ; Laryngeal Neoplasms/*diagnosis ; Male ; Mesothelioma/*diagnosis/etiology ; Occupational Diseases/diagnosis/etiology ; Pleural Neoplasms/diagnosis/etiology/*secondary ; }, abstract = {We describe an unusual case of metastatic poorly differentiated laryngeal carcinoma to the pleura resembling pleural mesothelioma in a patient with a positive history of exposure to asbestos. This case not only describes an unusual presentation of metastatic laryngeal carcinoma, but also highlights the need for special pathological techniques to distinguish nonmesothelial tumors from primary pleural mesotheliomas.}, } @article {pmid1669200, year = {1991}, author = {Stadnikova, NM and Kleĭmenova, EV and Grankina, EP and Pylev, LN}, title = {[The sodium selenite inhibition of asbestos-induced carcinogenesis in Wistar rats].}, journal = {Voprosy onkologii}, volume = {37}, number = {11-12}, pages = {1077-1081}, pmid = {1669200}, issn = {0507-3758}, mesh = {Animals ; Asbestos, Serpentine/administration & dosage/*toxicity ; Chi-Square Distribution ; Drug Evaluation, Preclinical ; Dust/adverse effects ; Female ; Male ; Pleural Neoplasms/*chemically induced/mortality/*prevention & control ; Rats ; Rats, Wistar ; Sodium Selenite/*administration & dosage ; }, abstract = {Sodium selenite given in drinking water in a 4 ppm solution during the whole experiment was found to significantly inhibit pleural carcinogenesis induced in Wistar rats by intrapleural injection of chrysotile-asbestos powder (20 mg three times, monthly, in 0.5 ml of physiologic saline). Mesothelioma of the pleura was induced in 20.5%. However, chrysotile alone induced tumor in 43.8%. Sodium selenite failed to influence carcinogenesis in other sites. Possible mechanisms of sodium selenite action are discussed.}, } @article {pmid1667980, year = {1991}, author = {Vasilewa, LA and Pylev, LN and Woźniak, H and Wiecek, E}, title = {Biological activity of synthetic amphibole asbestos.}, journal = {Polish journal of occupational medicine and environmental health}, volume = {4}, number = {1}, pages = {33-41}, pmid = {1667980}, issn = {0867-8383}, mesh = {Animals ; Asbestos/*toxicity ; Asbestos, Amphibole ; Carcinogens ; Chemical Phenomena ; Chemistry ; Mesothelioma/*etiology ; Neoplasms, Experimental/etiology ; Pleural Neoplasms/*etiology ; Rats ; Silicon Dioxide/*toxicity ; }, abstract = {The carcinogenic and fibrogenic activity of four samples of synthetic amphibole asbestos with different chemical structure was examined in white rats. Pleural mesotheliomas were found: in 11 out of 27 rats (37.8%) treated with magnesium asbestos; in 4 out of 24 animals (6.7%) for nickel asbestos; 13 out of 22 (59.1%) for cobalt asbestos; and in the experiment with asbestos where germanium was substituted for silicon pleural mesotheliomas were observed in 2 out of 55 rats (3.6%). No tumours of this kind were found in the control group. As revealed by the study results, all the examined samples of synthetic amphibole asbestos exhibited carcinogenic potentials. Correlation between the carcinogenic and fibrogenic activity could also be observed. The replacement of silicon with germanium produced considerable decrease in the carcinogenic and fibrogenic potentials of asbestos.}, } @article {pmid2077201, year = {1990}, author = {Hiraoka, T and Kiyota, S and Shima, K and Kinuwaki, E and Kimura, T and Fukuda, K and Shimazu, K and Teshima, Y and Izumi, K and Fukuda, Y}, title = {[Analysis of pleural plaque found at lung cancer screening examination].}, journal = {Nihon Kyobu Shikkan Gakkai zasshi}, volume = {28}, number = {12}, pages = {1566-1573}, pmid = {2077201}, issn = {0301-1542}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; *Environmental Exposure ; Humans ; Japan/epidemiology ; Lung Neoplasms/*prevention & control ; *Mass Screening ; Middle Aged ; Pleural Diseases/diagnostic imaging/*epidemiology/etiology ; Radiography ; }, abstract = {In the screening test of lung cancer, we found that there was a high prevalence of cases with pleural plaque recognized by chest X-ray film in inhabitants living in A town in Kumamoto Prefecture. We detected abnormal pleural plaque in 148 (41.5%) of 357 cases received lung cancer screening. These pleural plaques resulted in pleural thickening and calcification. Two or three mines of serpentine and an asbestos factory existed in this region from 1883 until 1970. Although twelve cases had a history of factory work, none had fibrous changes in the lung fields on chest X-ray films. It was considered that the pleural plaque probably resulted from exposure to low doses of asbestos in the atmosphere or contact with asbestos workers in their homes. The incidence of lung cancer in this region was not higher than that in other regions in Kumamoto Prefecture. There were no cases of malignant mesothelioma in our hospital during the past eleven years.}, } @article {pmid1965775, year = {1990}, author = {Luo, SQ and Liu, XE and Wang, CJ}, title = {Gross classification of 175 cases of rat pleural mesothelioma induced by chrysotile.}, journal = {Biomedical and environmental sciences : BES}, volume = {3}, number = {4}, pages = {378-383}, pmid = {1965775}, issn = {0895-3988}, mesh = {Animals ; Asbestos/*toxicity ; Asbestos, Serpentine ; Mesothelioma/classification/*etiology/pathology ; Pleural Neoplasms/classification/*etiology/pathology ; Rats ; }, abstract = {This paper reports an analysis of the gross pathologic classification of 175 cases of rat pleural mesothelioma induced by chrysotile. The mesotheliomas were divided into diffuse and localized types, and further into four subtypes according to the form of the tumors (massive, nodule, plaque, and mixed). Diffuse pleural mesothelioma accounted for 58.9% of the tumors and occurred mainly as the nodular type. Among the localized type (41.1%) the massive subtype was most prevalent.}, } @article {pmid1965774, year = {1990}, author = {Liu, XZ and Luo, SQ and Wang, CJ}, title = {The carcinogenicity of several species of asbestos produced in China.}, journal = {Biomedical and environmental sciences : BES}, volume = {3}, number = {4}, pages = {373-377}, pmid = {1965774}, issn = {0895-3988}, mesh = {Animals ; Asbestos/*toxicity ; Asbestos, Crocidolite ; Carcinogenicity Tests ; *Carcinogens ; Mesothelioma/*etiology ; Rats ; Rats, Inbred Strains ; }, abstract = {Cases of pleural mesothelioma induced by five species of chrysotile and three species of crocidolite from China in rats are compared. The rate of induction in the chrysotile group (43.1%) was slightly lower than that in the crocidolite group (56.7%). The survival time of the first case of mesothelioma in the chrysotile group was 408 days and in the crocidolite group 377 days. The major histological types of mesothelioma induced by chrysotile were epithelial and mixed, but the major type in the crocidolite group was fibrous. The extent of differentiation in all mesotheliomas, mainly intermediate and low, was nearly the same.}, } @article {pmid1974862, year = {1990}, author = {Bermudez, E and Everitt, J and Walker, C}, title = {Expression of growth factor and growth factor receptor RNA in rat pleural mesothelial cells in culture.}, journal = {Experimental cell research}, volume = {190}, number = {1}, pages = {91-98}, doi = {10.1016/0014-4827(90)90148-4}, pmid = {1974862}, issn = {0014-4827}, mesh = {Animals ; Cell Division/physiology ; Cell Separation ; Epithelial Cells ; ErbB Receptors/genetics ; Fibroblast Growth Factors/genetics ; Gene Expression Regulation ; Growth Substances/*genetics ; Humans ; In Vitro Techniques ; Platelet-Derived Growth Factor/genetics ; Pleura/*cytology ; Poly A/analysis ; RNA, Messenger/analysis ; Rats ; Rats, Inbred F344 ; Receptor, Insulin/genetics ; Receptors, Cell Surface/*genetics ; Receptors, Platelet-Derived Growth Factor ; Transforming Growth Factors/genetics ; }, abstract = {Mineral fiber-induced pleural mesothelioma in the rat is a suitable model for asbestos-induced mesothelioma in humans. A proposed mechanism for the genesis of mesotheliomas is the initiation of an autocrine pathway leading to unregulated growth of the mesothelium. To understand if changes in the expression of mRNA of critical growth factors and receptors occur in target mesothelial cells, it is first necessary to characterize the pattern of expression of these genes in normal mesothelial cells. Rat mesothelial cells were isolated from the parietal pleura and strains of these cells were propagated in vitro. The cells were diploid, had epithelial gross morphology and ultrastructure, and coexpressed keratins and vimentin. Northern blot analysis demonstrated that the cells expressed transforming growth factor beta 1 and fibroblast growth factor. Transcripts for transforming growth factor alpha, platelet-derived growth factor A-chain, and platelet-derived growth factor B-chain were not detected. Receptors for platelet-derived growth factor, epidermal growth factor, and insulin were detected. Although normal mesothelial cells express receptors for these growth factors, no production of their corresponding ligands by these cells could be detected, suggesting that autocrine stimulation of growth via the production of such factors may be specific to transformed mesothelial cells.}, } @article {pmid1700353, year = {1990}, author = {Hasse, J}, title = {[New challenges in thoracic surgery as exemplified in asbestos exposure and mesothelioma treatment].}, journal = {Das Offentliche Gesundheitswesen}, volume = {52}, number = {8-9}, pages = {512-518}, pmid = {1700353}, issn = {0029-8573}, mesh = {Aged ; Asbestosis/*complications ; Female ; Humans ; Male ; Mesothelioma/diagnosis/etiology/*surgery ; Middle Aged ; Palliative Care ; Pleura/surgery ; Pleural Neoplasms/diagnosis/etiology/*surgery ; Pneumonectomy ; Thoracoscopy ; Thoracotomy ; }, abstract = {The increasing production and use of asbestos has induced a steadily increasing incidence of malignant mesothelioma. Diagnostic difficulties persist and the disease may remain undiagnosed in spite of multiple fluid aspirations and percutaneous needle biopsies. Thoracic surgery efficiently contributes to the diagnostic yield by thoracoscopy and, with unilateral disease, in functionally operable patients, preferably by diagnostic thoracotomy. In suitable patients this can be extended to either palliative tumour pleurectomy or total pleuro-pneumonectomy en bloc with resection of the pericardium and the diaphragm. The primary mortality of this procedure has dropped from formerly thirty to now well below 10% for both types of resection. Along with any kind of thoracotomy a lung biopsy should be performed for search of asbestos bodies in the parenchyma. This will facilitate not only the differential diagnosis but also the answer to the question of aetiology in support of the patients' and their families' claim for compensation to be paid. Unfortunately, although surgery has advantages compared to chemo- or radiotherapy and improves the quality of life, it fails to achieve cure except in a few favourable cases.}, } @article {pmid1696007, year = {1990}, author = {Steinetz, C and Clarke, R and Jacobs, GH and Abdul-Karim, FW and Petrelli, M and Tomashefski, JF}, title = {Localized fibrous tumors of the pleura: correlation of histopathological, immunohistochemical and ultrastructural features.}, journal = {Pathology, research and practice}, volume = {186}, number = {3}, pages = {344-357}, doi = {10.1016/S0344-0338(11)80293-1}, pmid = {1696007}, issn = {0344-0338}, mesh = {Actins/metabolism ; Adult ; Aged ; Asbestos/analysis ; Cell Transformation, Neoplastic/metabolism/pathology/ultrastructure ; Desmin/metabolism ; Factor VIII/metabolism ; Female ; Humans ; Immunohistochemistry ; Keratins/metabolism ; Lung/analysis/pathology ; Lung Diseases/pathology ; Male ; Membrane Glycoproteins/metabolism ; Mesoderm/metabolism/pathology/ultrastructure ; Mesothelioma/metabolism/*pathology/ultrastructure ; Microscopy, Electron ; Middle Aged ; Mucin-1 ; Pleural Neoplasms/metabolism/*pathology/ultrastructure ; Vimentin/metabolism ; }, abstract = {The histogenesis of localized fibrous tumor of the pleura (LFTP) is controversial. We studied 12 LFTP's by light microscopy; by immunohistochemical staining for cytokeratin (CK), vimentin, muscle-specific actin, desmin, S-100 protein, epithelial membrane antigen (EMA) and factor VIII; by electron microscopy in 6 tumors; and by lung digestion for asbestos bodies in 4 cases. Three histologic patterns occurred in combination: 1) collagenous, 2) cellular and 3) hypocellular/myxoid. Hemangiopericytoma-like foci were prominent in the cellular areas of 9 tumors. Unusual features included diffuse small cells in 3 tumors, microcystic foci in 2, macrocystic areas in 5 and tumor giant cells in 4 tumors. Neoplastic cells in all patterns stained positively for vimentin and actin in 9 and 4 tumors, respectively, and were negative for all other markers. CK and EMA were identified in mesothelial and epithelial invaginations only. Ultrastructurally, neoplastic cells demonstrated intercellular junctions, intermediate or thin filaments, dense bodies and rough endoplasmic reticulum. Basal lamina was focally present in 5 tumors, while tonofilaments, desmosomes and short microvilli were observed in one case. Our results support the conclusion that LFTP is a neoplasm of the multipotential subserosal cell, and usually expresses mesenchymal (fibroblastic/myofibroblastic) differentiation. Coexpression of mesothelial features is rare. Lung asbestos body quantitation in 4 patients suggests that there is no association between LFTP and asbestos exposure.}, } @article {pmid1966004, year = {1990}, author = {Liu, XZ and Luo, SQ and Wang, ZM and Wang, MZ and Zhan, CL}, title = {An investigation of crocidolite contamination and mesothelioma in a rural area of China.}, journal = {Biomedical and environmental sciences : BES}, volume = {3}, number = {2}, pages = {156-165}, pmid = {1966004}, issn = {0895-3988}, mesh = {Asbestos/*adverse effects/analysis ; Asbestos, Crocidolite ; Carcinogens, Environmental/*adverse effects/analysis ; China/epidemiology ; Cohort Studies ; Humans ; Mesothelioma/epidemiology/*etiology/pathology/prevention & control ; Pleural Neoplasms/epidemiology/*etiology/pathology/prevention & control ; Retrospective Studies ; *Rural Health ; }, abstract = {Crocidolite was found to be ubiquitous in a county in southwestern China. It had been widely used in the making of road pavement, stoves, wall paint, etc. The environmental levels of the asbestos fibers were determined. Of the 2175 local residents examined, 16 had asbestosis and 232 had pleural plaques. These clinical manifestations were noted mainly in patients over 50 years of age.}, } @article {pmid1690413, year = {1990}, author = {Walz, R and Koch, HK}, title = {Malignant pleural mesothelioma: some aspects of epidemiology, differential diagnosis and prognosis. Histological and immunohistochemical evaluation and follow-up of mesotheliomas diagnosed from 1964 to January 1985.}, journal = {Pathology, research and practice}, volume = {186}, number = {1}, pages = {124-134}, doi = {10.1016/S0344-0338(11)81020-4}, pmid = {1690413}, issn = {0344-0338}, mesh = {Adult ; Age Factors ; Aged ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Humans ; Incidence ; Male ; Mesothelioma/epidemiology/*pathology ; Middle Aged ; Pleural Neoplasms/epidemiology/*pathology ; Staining and Labeling ; Survival Analysis ; }, abstract = {64 diffuse pleural mesotheliomas diagnosed between 1964 and January 1985 at the Institute of Pathology of the University of Freiburg were analyzed. Since 1980 an increase from one case to 10 cases per year has been observed. The tumor was 3 to 4 times more frequent in men than in women. The age distribution showed a peak between the age of 50 and 60. In 26 cases evidence of exposure to asbestos was detected. In one patient radiotherapy of Hodgkin's disease may have been of etiological significance. The median survival time was 13 months. The five-year survival rate was only 4%. Histologic reevaluation was only possible in cases diagnosed after 1975. Of 43 cases thus evaluated 26 were pure mesothelial, 15 biphasic and 2 of the spindle-cell subtype. A median survival time of 23 months for pure mesothelial mesothelioma in comparison to 13 months for the biphasic mesothelioma indicated a better prognosis for pure mesothelial mesothelioma. Although no other primary tumors were detected, in 10 cases the differential diagnosis of adenocarcinoma had to be considered, and in 3 cases tumors of non-epithelial origin had to be excluded. 35 of 43 mesothelioma were CEA-negative, 38 out of 43 cytokeratin-positive, and 33 out of 43 were EMA-positive. Factor-VIII-related antigen was not demonstrated. 12 of 43 mesotheliomas showed PAS-positive staining, 29 of 43 were stained with Alcian blue. 7 of these 29 showed a positive digestion with hyaluronidase. Although CEA may not be negative in every mesothelioma, this marker seems to be a valid tool for the differential diagnosis of adenocarcinoma. In order to safeguard against a mistaken diagnosis of pleural mesothelioma, the exclusion of other tumors is always indispensable.}, } @article {pmid1670293, year = {1990}, author = {Huuskonen, MS}, title = {[Diseases caused by asbestos today].}, journal = {Duodecim; laaketieteellinen aikakauskirja}, volume = {106}, number = {10}, pages = {787-789}, pmid = {1670293}, issn = {0012-7183}, mesh = {Asbestos/*adverse effects ; Asbestosis/etiology ; Finland/epidemiology ; Humans ; Lung Neoplasms/epidemiology/etiology ; Mesothelioma/epidemiology/etiology ; Pleural Diseases/etiology ; }, } @article {pmid548972, year = {1979}, author = {Lob, M}, title = {[Asbestos-related diseases (author's transl)].}, journal = {Schweizerische Rundschau fur Medizin Praxis = Revue suisse de medecine Praxis}, volume = {68}, number = {52}, pages = {1717-1723}, pmid = {548972}, issn = {1013-2058}, mesh = {Adult ; Asbestosis/*complications ; Environmental Pollution/prevention & control ; Humans ; Lung Neoplasms/*chemically induced ; Mesothelioma/*chemically induced ; Switzerland ; }, } @article {pmid540105, year = {1979}, author = {Davis, JM}, title = {The histopathology and ultrastructure of pleural mesotheliomas produced in the rat by injections of crocidolite asbestos.}, journal = {British journal of experimental pathology}, volume = {60}, number = {6}, pages = {642-652}, pmid = {540105}, issn = {0007-1021}, mesh = {Animals ; Asbestos/*toxicity ; Mesothelioma/etiology/*ultrastructure ; Microscopy, Electron ; Pleural Neoplasms/etiology/*ultrastructure ; Rats ; }, abstract = {Primary tumours of the pleural cavity were produced in rats by the intrapleural injection of crocidolite asbestos. Their histological structure as seen with both light and electron microscopy was very variable and tumours frequently contained elements of both connective-tissue and epithelial type. In some instances the connective-tissue elements predominated from the start and the earliest tumour nodules consisted mainly of pleomorphic connective-tissue cells with only a few layers of cells more nearly epithelial in type on the surface. This pattern was largely retained when tumour nodules increased in size and coalesced, but in the deeper layers of advanced tumours the pleomorphic connective-tissue pattern was often replaced by a more uniform spindle-cell form. Other tumours were more predominantly epithelial in type, showing either a papillary pattern with rounded epithelial cells growing in solid columns, or a vesicular form in which large tissue spaces, often intracellular, were lined by very thin layers of extended cell cytoplasm. Whereas early tumours showed only one histological pattern, the more advanced stages often exhibited areas of all 3, so that there seemed to be some degree of histological mutability. The spindle-cell areas of advanced tumours frequently showed evidence of direct invasion of the surrounding tissue but this was never seen with the epithelial forms of rat mesothelioma.}, } @article {pmid233434, year = {1979}, author = {Baris, I and Artvinli, M and Sahin, A and Savas, T and Erkan, ML}, title = {[Occurrence of pleural mesothelioma. Chronic fibrosing pleurisy and calcified pleural plaques in Turkey in relation with environmental pollution by mineral fibers (author's transl)].}, journal = {Revue francaise des maladies respiratoires}, volume = {7}, number = {7}, pages = {687-694}, pmid = {233434}, issn = {0301-0279}, mesh = {Air Pollutants/*adverse effects ; Aluminum Silicates/adverse effects ; Asbestos/adverse effects ; Humans ; Mesothelioma/*epidemiology/etiology ; Minerals/*adverse effects ; Pleural Diseases/*epidemiology/etiology ; Pleural Neoplasms/*epidemiology/etiology ; Pleurisy/*epidemiology/etiology ; Turkey ; Zeolites ; }, abstract = {The incidence of pleural mesothelioma (PM), chronic fibrosing pleurisy (CFP) and calcified pleural plaques (CPP) has been studied in Anatolia (Turkey) in relation with environmental pollution by mineral fibers: 1) In central Anatolia, where asbestos deposits have been described, the frequency of CFP and CPP was in the range 2-25%; several cases of PM have been encountered. 2) One area (Cappadoce) is free of asbestos, but contains another kind of mineral fiber: zeolite. In this area, an outbreak of PM has been described in some villages. Among the 600 inhabitants of Karain, 28 cases of PM occurred for the period January 1975-June 1979.}, } @article {pmid91808, year = {1979}, author = {McDonald, G and McDonald, A}, title = {Age and latency in mesothelioma.}, journal = {Lancet (London, England)}, volume = {2}, number = {8151}, pages = {1074}, doi = {10.1016/s0140-6736(79)92468-1}, pmid = {91808}, issn = {0140-6736}, mesh = {Adult ; Age Factors ; Aged ; Asbestos/adverse effects ; Canada ; Female ; Humans ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; Middle Aged ; Occupational Diseases/*mortality ; United States ; }, } @article {pmid316753, year = {1979}, author = {Wagner, MM and Campbell, MJ and Edwards, RE}, title = {Sequential immunological studies on an asbestos-exposed population. I. Factors affecting peripheral blood leucocytes and T lymphocytes.}, journal = {Clinical and experimental immunology}, volume = {38}, number = {2}, pages = {323-331}, pmid = {316753}, issn = {0009-9104}, mesh = {Adult ; Aging ; Asbestos/*pharmacology ; Bronchitis/blood ; Chronic Disease ; Circadian Rhythm ; Esterases ; Humans ; Leukocyte Count ; Leukocytes/drug effects/*immunology ; Lymphocytes/enzymology ; Male ; Mesothelioma/blood ; Middle Aged ; Pleura/pathology ; Pleural Diseases/blood ; Respiratory Function Tests ; Rhinitis, Allergic, Seasonal/blood ; Rosette Formation ; Smoking ; T-Lymphocytes/drug effects/*immunology ; X-Rays ; }, abstract = {Peripheral blood leucocyte counts, and E binding rosettes were measured on 138 men on five separate occasions. Little effect was seen from age, or length of asbestos exposure. Overall the most marked effect was that obtained from smoking. Most relevant was an increase in percentage of E-rosettes read after 1 1/2 hrs, which was obtained in the group of those with radiological evidence of fibrosis who smoked. Restricted to subjects with small opacities, those who smoke have a significantly higher (P less than 0.05) percentage E 1 1/2 hr rosettes than those who do not smoke. (Percentage E rosettes read overnight remained unaltered by smoking or X-ray). This increase was found on each occasion that it was measured. Since the absolute number of T lymphocytes rosetting at 1 1/2 hr did not increase, it is suggested that there is either no stimulation of the central pool of T lymphocytes or a decrease in the absolute number of T lymphocytes which could only rosette overnight.}, } @article {pmid90947, year = {1979}, author = {Chovil, A and Stewart, C}, title = {Latency period for mesothelioma.}, journal = {Lancet (London, England)}, volume = {2}, number = {8147}, pages = {853}, doi = {10.1016/s0140-6736(79)92205-0}, pmid = {90947}, issn = {0140-6736}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Middle Aged ; Occupational Diseases/*etiology ; Time Factors ; }, } @article {pmid114796, year = {1979}, author = {}, title = {[How dangerous is asbestos dust?].}, journal = {MMW, Munchener medizinische Wochenschrift}, volume = {121}, number = {39}, pages = {1236-1237}, pmid = {114796}, issn = {0341-3098}, mesh = {Asbestos/*adverse effects ; Asbestosis/etiology ; Dust ; Humans ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Occupational Diseases ; }, } @article {pmid518322, year = {1979}, author = {Kovac-Stojkovski, S}, title = {[Exposure to asbestos and pleural mesothelioma].}, journal = {Arhiv za higijenu rada i toksikologiju}, volume = {30}, number = {3}, pages = {267-291}, pmid = {518322}, issn = {0004-1254}, mesh = {Adolescent ; Adult ; Aged ; Asbestos/*adverse effects ; Environmental Exposure ; Female ; Humans ; Male ; Mesothelioma/epidemiology/*etiology ; Middle Aged ; Occupational Diseases/epidemiology/etiology ; Pleural Neoplasms/epidemiology/*etiology ; }, } @article {pmid476600, year = {1979}, author = {Stock, RJ and Fu, YS and Carter, JR}, title = {Malignant peritoneal mesothelioma following radiotherapy for seminoma of the testis.}, journal = {Cancer}, volume = {44}, number = {3}, pages = {914-919}, doi = {10.1002/1097-0142(197909)44:3<914::aid-cncr2820440319>3.0.co;2-b}, pmid = {476600}, issn = {0008-543X}, mesh = {Dysgerminoma/*radiotherapy ; Humans ; Male ; Mesothelioma/diagnosis/*etiology ; Microscopy, Electron ; Middle Aged ; Neoplasms, Multiple Primary/diagnosis/*etiology ; *Neoplasms, Radiation-Induced/diagnosis ; Peritoneal Neoplasms/diagnosis/*etiology ; Testicular Neoplasms/*radiotherapy ; Time Factors ; }, abstract = {The difficulties encountered in establishing a diagnosis of a malignant peritoneal mesothelioma are emphasized in a patient who developed the lesion 16 years after radiation therapy for a seminoma of the testis. Historically, histologically, electron microscopically, and by microincineration, there was no evidence of asbestos exposure. We believe that present lesion may be a consequence of prior radiation therapy.}, } @article {pmid467106, year = {1979}, author = {Becklake, MR}, title = {Environmental exposure to asbestos: A factor in the rising rate of cancer in the industrialized world?.}, journal = {Chest}, volume = {76}, number = {3}, pages = {245-247}, doi = {10.1378/chest.76.3.245}, pmid = {467106}, issn = {0012-3692}, mesh = {Asbestos/*adverse effects ; Environmental Pollutants/*adverse effects ; Gastrointestinal Neoplasms/chemically induced ; Humans ; Lung Neoplasms/*chemically induced ; Mesothelioma/*chemically induced ; Occupational Diseases/chemically induced ; Smoking/complications ; }, } @article {pmid89403, year = {1979}, author = {Longo, DL and Young, RC}, title = {Cosmetic talc and ovarian cancer.}, journal = {Lancet (London, England)}, volume = {2}, number = {8138}, pages = {349-351}, doi = {10.1016/s0140-6736(79)90357-x}, pmid = {89403}, issn = {0140-6736}, mesh = {Adult ; Animals ; Asbestos/adverse effects ; Carcinogens ; Cosmetics/*adverse effects ; Cricetinae ; Female ; Guinea Pigs ; Humans ; Mesothelioma/*etiology ; Mice ; Middle Aged ; Occupational Diseases/etiology ; Ovarian Neoplasms/*etiology ; Rabbits ; Rats ; Talc/*adverse effects ; United States ; }, } @article {pmid500777, year = {1979}, author = {Rubino, GF and Piolatto, G and Newhouse, ML and Scansetti, G and Aresini, GA and Murray, R}, title = {Mortality of chrysotile asbestos workers at the Balangero Mine, Northern Italy.}, journal = {British journal of industrial medicine}, volume = {36}, number = {3}, pages = {187-194}, pmid = {500777}, issn = {0007-1072}, mesh = {Asbestos/*adverse effects ; Asbestosis/mortality ; Humans ; Italy ; Laryngeal Neoplasms/mortality ; Lung Neoplasms/mortality ; Male ; *Mining ; Occupational Diseases/etiology/*mortality ; Smoking/complications ; }, abstract = {The mortality from 1946 to 1975 of over 900 North Italian chrysotile asbestos workers first employed between 1930 and 1965 has been studied. Nine deaths were certified as attributable to asbestosis, and eleven to lung cancer. One death was attributed to mesothelioma of pleura but this diagnosis was not supported by histological examination. Comparison with the national figures for all Italy did not reveal an excess of deaths from lung cancer but during the last quinquennium of observation, the SMR for lung cancer rose to 206. Simulation experiments enabled a dust index in fibre/years to be attached to each man in the cohort. All but two of the deaths from lung cancer occurred in the higher exposure group. The relative risk of lung cancer in this group was 2.89. The eleven workers who died from lung cancer were all cigarette smokers. A further period of observation is required to monitor the mortality of the surviving workers.}, } @article {pmid313709, year = {1979}, author = {Kagan, E and Jacobson, RJ and Yeung, KY and Haidak, DJ and Nachnani, GH}, title = {Asbestos-associated neoplasms of B cell lineage.}, journal = {The American journal of medicine}, volume = {67}, number = {2}, pages = {325-330}, doi = {10.1016/0002-9343(79)90408-x}, pmid = {313709}, issn = {0002-9343}, mesh = {Aged ; Asbestos/*adverse effects ; Asbestosis/*complications ; B-Lymphocytes/*immunology ; Environmental Exposure ; Humans ; Immunity, Cellular ; Immunoglobulin A/analysis ; Immunoglobulin G/analysis ; Leukemia, Lymphoid/*etiology ; Male ; Mesothelioma/etiology ; Middle Aged ; Multiple Myeloma/*etiology ; Pleural Neoplasms/etiology ; }, abstract = {Three different neoplasms of B cell lineage, chronic lymphocytic leukemia, immunoglobulin A (IgA) myeloma and immunoglobulin G (IgG) myeloma were detected in three patients who had heavy occupational exposure to asbestos dust. Two of the patients had coexistent pulmonary asbestosis, whereas the third patient had a pleural mesothelioma subsequent to his initial presentation with myeloma. Defective cell-mediated immunity and hyperactivity of B cell function have previously been noted in patients with asbestosis. We suggest the possibility that these asbestos-related immunologic derangements may predispose to the development of immunoproliferative and lymphoproliferative neoplasms, since such tumors have been observed in a variety of other settings, characterized by protracted hyperactivity of the immune system.}, } @article {pmid227674, year = {1979}, author = {Stevens, RH and Will, LA and Cole, DA and Meek, ES and Frank, CW and Donham, KJ}, title = {Cyclic nucleotide concentrations in asbestos-induced rat peritoneal mesothelioma.}, journal = {Environmental research}, volume = {19}, number = {2}, pages = {442-448}, doi = {10.1016/0013-9351(79)90069-0}, pmid = {227674}, issn = {0013-9351}, mesh = {Animals ; *Asbestos ; Cyclic AMP/*metabolism ; Cyclic GMP/*metabolism ; Male ; Mesothelioma/etiology/*metabolism/pathology ; Neoplasms, Experimental/metabolism ; Peritoneal Neoplasms/etiology/*metabolism/pathology ; Rats ; }, } @article {pmid482244, year = {1979}, author = {Wagner, JC}, title = {Diseases associated with exposure to asbestos dusts.}, journal = {The Practitioner}, volume = {223}, number = {1333}, pages = {28-33}, pmid = {482244}, issn = {0032-6518}, mesh = {Asbestos/*adverse effects ; Asbestosis/etiology ; Environmental Exposure ; Female ; Humans ; Lung Diseases/*etiology ; Lung Neoplasms/epidemiology/etiology ; Male ; Mesothelioma/epidemiology/etiology ; Occupational Diseases/*etiology ; Peritoneal Neoplasms/etiology ; Pleural Diseases/etiology ; Pleural Neoplasms/etiology ; United Kingdom ; }, } @article {pmid475466, year = {1979}, author = {Acheson, ED and Gardner, MJ}, title = {Mesothelioma and exposure to mixtures of chrysotile and amphibole asbestos.}, journal = {Archives of environmental health}, volume = {34}, number = {4}, pages = {240-242}, doi = {10.1080/00039896.1979.10667406}, pmid = {475466}, issn = {0003-9896}, mesh = {*Asbestos/classification ; Environmental Exposure ; Humans ; Lung Neoplasms/*chemically induced ; Mesothelioma/*chemically induced ; Structure-Activity Relationship ; }, abstract = {This paper provides a new analysis of previously published work and draws attention to the possibility that mixtures of amphiboles and chrysotile appear more commonly in the lungs of mesothelioma patients compared to controls than do either of the main types of fiber alone. The possibility that these results may indicate a synergistic interaction between chrysotile and the amphiboles is discussed in the light of the epidemiological data.}, } @article {pmid463903, year = {1979}, author = {}, title = {Fever, hepatic lesions and ascites.}, journal = {The American journal of medicine}, volume = {67}, number = {1}, pages = {105-112}, doi = {10.1016/0002-9343(79)90080-9}, pmid = {463903}, issn = {0002-9343}, mesh = {Asbestos/adverse effects ; Humans ; Male ; Mesothelioma/etiology/*pathology ; Middle Aged ; Occupational Diseases/etiology ; Peritoneal Neoplasms/etiology/*pathology ; }, } @article {pmid286826, year = {1979}, author = {Artvinli, M and Bariş, YI}, title = {Malignant mesotheliomas in a small village in the Anatolian region of Turkey: an epidemiologic study.}, journal = {Journal of the National Cancer Institute}, volume = {63}, number = {1}, pages = {17-22}, pmid = {286826}, issn = {0027-8874}, mesh = {Adult ; Age Factors ; Aged ; Asbestos/adverse effects ; Female ; Humans ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Pleural Neoplasms/*epidemiology ; Sex Factors ; Smoking/epidemiology ; Turkey ; }, abstract = {An epidemiologic and cause-related study was done in Tuzköy, a small village in the city of Nevşehir, in the Anatolian region of Turkey. The neighboring village of Kizilböy was used as a control. People 25 years of age or older were studied: 312 persons (145 males and 167 females) from Tuzköy and 95 persons (45 males and 50 females) from the control village. The annual incidence of malignant pleural mesothelioma (MPM) was found to be 6.5 cases (22 cases per 10,000 people) in Tuzköy. Several other respiratory disorders were detected as well. Although no type of asbestos could be found in Tuzköy and its vicinity, the asbestiform mineral zeolite was found in soil samples from the roads and fields of Tuzköy, in its building stones, and in lung tissues of the villagers. Chest X-rays revealed no cases of MPM or other respiratory abnormalities in the control group. No zeolite could be found in the control village. Therefore, zeolite was thought to be the cause of MPM and the other respiratory disorders in Tuzköy.}, } @article {pmid468415, year = {1979}, author = {Kanazawa, K and Roe, FJ and Yamamoto, T}, title = {Milky spots (Taches laiteuses) as structures which trap asbestos in mesothelial layers and their significance in the pathogenesis of mesothelial neoplasia.}, journal = {International journal of cancer}, volume = {23}, number = {6}, pages = {858-865}, doi = {10.1002/ijc.2910230619}, pmid = {468415}, issn = {0020-7136}, mesh = {Animals ; *Asbestos ; Carcinogens ; Female ; Injections, Intravenous ; Injections, Subcutaneous ; Mesothelioma/blood supply/*etiology/ultrastructure ; Mice ; Mice, Inbred CBA ; Neoplasms, Experimental/blood supply/etiology/ultrastructure ; }, abstract = {The UICC standard sample of asbestos, crocidolite, was injected subcutaneously into the flanks of CBA/lac mice. Asbestos fibres were found in milky spots in the serosal cavities more than 442 days after the injection, in the form of either naked fibres or asbestos bodies. Milky spots were the only structure in which asbestos fibres were observed in the mesothelial layer. The fact that asbestos fibres were found in the liver, spleen, kidney, brain, etc., in addition to milky spots, suggested that they were transported by the blood stream throughout the body. This assumption was confirmed by the similar distribution of asbestos after intravenous administration. The vascular and cellular structure of milky spots is such that they are particularly likely to trap blood-borne asbestos fibres. Hyperplastic changes were observed in milky spots after both subcutaneous and intravenous administration of asbestos in mice. The possible involvement of milky spots in the genesis of tumors of the mesothelium following exposure of animals to asbestos is discussed.}, } @article {pmid223995, year = {1979}, author = {Kanazawa, K and Yamamoto, T and Yuasa, Y}, title = {Enhancement by asbestos of oncogenesis by Moloney murine sarcoma virus in CBA mice.}, journal = {International journal of cancer}, volume = {23}, number = {6}, pages = {866-874}, doi = {10.1002/ijc.2910230620}, pmid = {223995}, issn = {0020-7136}, mesh = {Animals ; *Asbestos/administration & dosage ; Carcinogens ; Injections, Intraperitoneal ; Leukemia, Experimental/*immunology ; Mesothelioma/*etiology/immunology/pathology ; Mice ; Mice, Inbred CBA ; Moloney murine leukemia virus/immunology ; Neoplasms, Experimental/etiology/immunology/pathology ; Sarcoma Viruses, Murine/immunology ; Sarcoma, Experimental/*immunology ; }, abstract = {Five micrograms of finely ground crocidolite asbestos (UICC standard sample) were injected intraperitoneally into 3-week-old CBA mice, together with 10(5) FFU of Moloney murine sarcoma virus. Altogether 44 out of 61 mice (72.1%) so treated developed palpable intraperitoneal tumours, and half of these died of such tumours within 100 days. The same amount of quartz and carbon similarly administered gave lower tumour incidences, namely, 19.4% (3.2% fatal) and 11.9% (1.5% fatal) respectively. Only 1 out of 59 mice inoculated with the virus alone developed a palpable intraperitoneal tumour, and this regressed spontaneously within 10 days of its first appearance. No tumours were encountered in mice treated with either asbestos, quartz or carbon alone. All the neoplasms had the appearance, under the light microscope, of anaplastic sarcomas. Most of them were confined to the serosal surface of the abdominal cavity, although invasion of underlying tissues was observed in some of the animals that died. Electron microscopical examination of tumours revealed the presence of C-type particles budding off from cellular surface. Some neoplastic cells showed characteristic features of mesothelial lining cells. The role of milky spots (taches laiteuses) in oncogenesis by asbestos and virus, especially in the induction of mesothelioma, is discussed.}, } @article {pmid493705, year = {1979}, author = {Bignon, J and Sébastien, P and Di Menza, L and Nebut, M and Payan, H}, title = {[French mesothelioma register 1965-1978 (author's transl)].}, journal = {Revue francaise des maladies respiratoires}, volume = {7}, number = {3}, pages = {223-241}, pmid = {493705}, issn = {0301-0279}, mesh = {Adult ; Age Factors ; Aged ; *Air Pollutants ; *Air Pollutants, Occupational ; *Asbestos ; Diagnosis, Differential ; Environmental Exposure ; Epidemiologic Methods ; Female ; France ; Heart Neoplasms/*epidemiology/mortality/pathology ; Humans ; Male ; Mesothelioma/*epidemiology/mortality/pathology ; Middle Aged ; Peritoneal Neoplasms/*epidemiology/mortality/pathology ; Pleura/pathology ; Pleural Neoplasms/*epidemiology/mortality/pathology ; *Registries ; Sex Factors ; }, abstract = {A mesothelioma register was initiated in France in 1975 to record pathologists, cases diagnosed since 1965. These cases have been accepted as definite mesothelioma after histological reexamination by the mesothelioma panel. Histories of asbestos exposure have been recorded using a standardized questionnaire. Among 699 cases reported, 296 were confirmed and 79 excluded by the panel. Twenty per cent of cases were females. Tumour was located in the pleura in 96% of cases. Age at death was lower for the mesothelioma group than for the general population. A linear increase of annual incidence since 1965 has been observed. Mapping of cases showed irregular distribution with areas without any case. Distribution of cases according to asbestos exposure was the following: definite occupational history 50%, definite non-occupational 3%, possible occupational 31%, undiscovered 16%. Distribution of cases according to the latency period showed a two peaks-curve, median being 36 years. The obvious under-reporting of cases and the absence of control group greatly affected the validity of some results.}, } @article {pmid452903, year = {1979}, author = {Kawai, T}, title = {Histopathological studies on experimentally induced pulmonary, pleural and peritoneal neoplasms in mice by intraperitoneal injection of chrysotile asbestos and N-methyl-N-nitrosourethane.}, journal = {Acta pathologica japonica}, volume = {29}, number = {3}, pages = {421-433}, doi = {10.1111/j.1440-1827.1979.tb00199.x}, pmid = {452903}, issn = {0001-6632}, mesh = {Adenocarcinoma/chemically induced/pathology ; Animals ; Asbestos/administration & dosage/*adverse effects ; Female ; Injections, Intraperitoneal ; Lung Neoplasms/chemically induced/etiology/*pathology ; Male ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Neoplasms, Experimental/chemically induced/etiology/pathology ; *Nitrosomethylurethane/administration & dosage ; Peritoneal Neoplasms/chemically induced/etiology/*pathology ; Pleural Neoplasms/chemically induced/etiology/*pathology ; Sarcoma, Experimental/etiology/pathology ; Transplantation, Homologous ; *Urethane/analogs & derivatives ; }, abstract = {The cocarcinogenic effects of asbestos are presented. In lung carcinomas induced in mice, the number of carcinomas and the time of detection of the first carcinoma per tumor-bearing animals were greater and faster in the group with chrysotile plus MNU than either chrysotile or MNU alone. This suggested that chrysotile asbestos had a promoting or cocarcinogenic effect on some carcinogens in the respiratory tract. In the group treated with chryotile alone, a tumor was found in the right pleural cavity at 15 months. This tumor microscopically was similar to the biphasic form of the human diffuse mesothelioma. Microvilli, basement membrane, and junctional apparatus were seen by electron microscope, but other cytoplasmic organelles of the tumor cells were relatively scanty. Two peritoneal tumors developed in gastric and intestinal serosa at 11 and 12 months. Light and electron microscopic studies suggested that the tumors were probably myosarcomas or fibrosarcoms.}, } @article {pmid377270, year = {1979}, author = {Worth, G and Worth, H}, title = {[Diseases due to the inhalation of asbestos dust].}, journal = {Praxis und Klinik der Pneumologie}, volume = {33}, number = {5}, pages = {701-725}, pmid = {377270}, issn = {0342-7498}, mesh = {Asbestos/analysis ; *Asbestosis/complications/diagnostic imaging/etiology ; Dust ; Environmental Health ; Humans ; Lung/diagnostic imaging/pathology ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Microscopy, Electron, Scanning ; Neoplasms/etiology ; Pneumoconiosis/classification ; Radiography ; Tuberculosis, Pulmonary/complications ; }, } @article {pmid389621, year = {1979}, author = {Lee, DH and Selikoff, IJ}, title = {Historical background to the asbestos problem.}, journal = {Environmental research}, volume = {18}, number = {2}, pages = {300-314}, doi = {10.1016/0013-9351(79)90107-5}, pmid = {389621}, issn = {0013-9351}, mesh = {Asbestos/adverse effects/*history ; Asbestosis/epidemiology/etiology/*history ; Canada ; Carcinoma, Bronchogenic/epidemiology ; Finland ; History, 15th Century ; History, 16th Century ; History, 17th Century ; History, 18th Century ; History, 19th Century ; History, 20th Century ; History, Ancient ; History, Medieval ; Humans ; Industry ; Italy ; Mesothelioma/epidemiology ; Pleural Diseases/complications/epidemiology ; Pleural Neoplasms/epidemiology ; Pulmonary Fibrosis/complications/epidemiology ; South Africa ; USSR ; United States ; }, } @article {pmid494698, year = {1979}, author = {Beck, B and Irmscher, G}, title = {[Extrathoracic mesothelioma by inhalation of asbestos dust (author's transl)].}, journal = {Zeitschrift fur Erkrankungen der Atmungsorgane}, volume = {152}, number = {3}, pages = {282-293}, pmid = {494698}, issn = {0303-657X}, mesh = {Asbestos/*adverse effects ; Berlin ; Female ; Humans ; Male ; Maximum Allowable Concentration ; Mesothelioma/diagnosis/epidemiology/*etiology ; Occupational Diseases/*etiology ; Peritoneal Neoplasms/diagnosis/epidemiology/*etiology ; }, abstract = {Report on 22 cases of malign peritoneal mesothelioma, their occupational, epidemiological, differentialdiagnostic, and oncologic aspects being discussed. For expert opinion the special criteria for acknowledging a peritoneal mesothelioma as an occupational disease are formulated (time and level to asbestos exposition, presence of pulmonary asbestosis and/or asbestos needles, latency time of about 20 years, and malignancy of the very often diffuse peritoneal mesothelioma).}, } @article {pmid465302, year = {1979}, author = {Wagner, MM}, title = {Thymectomy and asbestos-induced mesotheliomas in rats.}, journal = {British journal of cancer}, volume = {39}, number = {3}, pages = {337-341}, pmid = {465302}, issn = {0007-0920}, mesh = {Animals ; Animals, Newborn ; Asbestos/*toxicity ; Female ; Lung Neoplasms/*etiology ; Male ; Mesothelioma/*etiology ; Rats ; *Thymectomy ; Time Factors ; }, } @article {pmid490461, year = {1979}, author = {Delumeau, J and Crochet, D and Petitier, H and Loire, JM and Devineau, L and Herzog, B}, title = {[The value of Mackenzie and Harries's technique in detecting pleural thickenings: results of a systematic study in 64 patients exposed to the risk of asbestosis (author's transl)].}, journal = {Journal de radiologie}, volume = {60}, number = {2}, pages = {101-104}, pmid = {490461}, issn = {0221-0363}, mesh = {Aged ; Asbestosis/*diagnostic imaging ; Calcinosis/diagnostic imaging ; Humans ; Lung/diagnostic imaging ; Methods ; Middle Aged ; Occupational Diseases/diagnostic imaging ; Pleural Diseases/*diagnostic imaging ; Radiography ; }, abstract = {The authors stress the difficulty of detecting pleural thickenings due to asbestos by radiography, before the late stage when calcification appears. Using Mackenzie and Harries's technique, they radiographed 64 subjects working in the naval shipbuilding yard in Nantes, who had previously been examined by radiophotography. Their results confirmed the superiority of the 45 degrees oblique incidence for demonstrating patches of pleural thickening in those areas where they occur most frequently. The value of this early detection is purely social and occupational at the present time, as it cannot be used to give a prognosis as to the possible appearance of a more serious lesion such as mesotheliomas.}, } @article {pmid555440, year = {1979}, author = {Huuskonen, MS}, title = {[Health hazards of asbestos].}, journal = {Duodecim; laaketieteellinen aikakauskirja}, volume = {95}, number = {18}, pages = {1116-1118}, pmid = {555440}, issn = {0012-7183}, mesh = {Asbestos/*adverse effects ; Asbestosis/complications ; Humans ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Stomach Neoplasms/etiology ; }, } @article {pmid498729, year = {1979}, author = {}, title = {Asbestos exposure: a desk reference for communicators. National Cancer Institute.}, journal = {Clinical toxicology}, volume = {14}, number = {5}, pages = {607-618}, doi = {10.3109/15563657908992472}, pmid = {498729}, issn = {0009-9309}, mesh = {Asbestos/*poisoning ; Asbestosis/complications ; Communication ; Government Agencies ; Humans ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; *Occupational Diseases ; Risk ; Smoking/complications ; United States ; }, } @article {pmid459514, year = {1979}, author = {Mischler, NE and Chuprevich, T and Johnson, RO and Tormey, DC}, title = {Malignant mesothelioma presenting in the pleura and peritoneum.}, journal = {Journal of surgical oncology}, volume = {11}, number = {3}, pages = {185-191}, doi = {10.1002/jso.2930110302}, pmid = {459514}, issn = {0022-4790}, mesh = {Adult ; Dacarbazine/administration & dosage ; Doxorubicin/administration & dosage ; Drug Therapy, Combination ; Humans ; Male ; Mesothelioma/*diagnosis/drug therapy ; Peritoneal Neoplasms/*diagnosis/drug therapy ; Pleural Neoplasms/*diagnosis/drug therapy ; Tomography, X-Ray Computed ; }, abstract = {Malignant mesothelioma presenting in the pleura and peritoneum is described in a middle-aged man. The patient lacked significant asbestos exposure which is not unexpected from both the clinical literature and animal inhalation tumor data. Computerized axial tomographic correlation is provided. Partial remission was achieved with the administration of adriamycin and DTIC.}, } @article {pmid435375, year = {1979}, author = {Elmes, P}, title = {Asbestosis and mesothelioma [proceedings].}, journal = {British journal of diseases of the chest}, volume = {73}, number = {1}, pages = {50-51}, pmid = {435375}, issn = {0007-0971}, mesh = {Adult ; Asbestos/adverse effects ; Asbestosis/etiology ; Female ; Humans ; Lung Neoplasms/*etiology ; Male ; Mesothelioma/*etiology ; Northern Ireland ; Occupational Diseases/etiology ; }, } @article {pmid434717, year = {1979}, author = {Emonot, A and Marquet, M and Baril, A and Berardj, and Braillon, }, title = {[Epidemiology of asbestos-induced mesotheliomas in inhabitants of the Saint-Etienne area. Apropos of 35 cases].}, journal = {Annales de medecine interne}, volume = {130}, number = {2}, pages = {71-74}, pmid = {434717}, issn = {0003-410X}, mesh = {Air Pollutants/analysis ; Asbestos/*adverse effects/analysis ; Follow-Up Studies ; France ; Humans ; Mesothelioma/epidemiology/*etiology/pathology ; Pleural Neoplasms/epidemiology/*etiology/pathology ; }, abstract = {The 35 cases reviewed in this study provided evidence that apart from occupational dust hazards there could be a risk of asbestos dust contamination which is not related to working conditions but occurs through urban and industrial pollution.}, } @article {pmid423543, year = {1979}, author = {Pigott, GH and Ishmael, J}, title = {Toxicological assessment of potential hazards from new inorganic fibres.}, journal = {The Journal of the Society of Occupational Medicine}, volume = {29}, number = {1}, pages = {20-21}, doi = {10.1093/occmed/29.1.20}, pmid = {423543}, issn = {0301-0023}, mesh = {Aluminum/*toxicity ; Aluminum Oxide/*toxicity ; Animals ; Asbestos/*toxicity ; Lung/drug effects ; Lung Neoplasms/chemically induced ; Mesothelioma/chemically induced ; Rats ; }, } @article {pmid378818, year = {1979}, author = {Newhouse, ML}, title = {The asbestos industry and statutory control of its hazards.}, journal = {IARC scientific publications}, volume = {}, number = {25}, pages = {59-70}, pmid = {378818}, mesh = {Asbestos/standards ; Asbestosis/history/*prevention & control ; History, 20th Century ; Humans ; *Legislation as Topic ; Lung Neoplasms/etiology ; Maximum Allowable Concentration ; Mesothelioma/etiology ; United Kingdom ; United States ; }, abstract = {The difficulties of balancing the possible hazards of asbestos against its useful properties, the cost of control measures and the availability of adequate substitutes are described. The history of the asbestos industry, of recognition of the association between asbestos and respiratory disease and of the develpment of control regulations in the UK are outlined. The present provisions for inspection of work places, for medical services to workers and for environmental control within and outside the workplace have been reviewed and a Health and Safety Commission set up to implement them; their work is described. Although the regulations are being implemented, however, public anxiety has increased. Justification for such anxiety comes from reports of still-existing hazards and from the fact that the current standard was established on faulty grounds. Three studies are described which indicate that a dose-response relationship may exist in relation to the carcinogenicity of asbestos; however, there is still not enough evidence to set standards. Further studies have shown that the different types of asbestos incur different degrees of risk. The UK Asbestos Standards are thus undergoing revision, this time in consultation not only with physicians and hygienists, but also with members of industry, trades union members, academics and local authorities.}, } @article {pmid316663, year = {1979}, author = {Gregor, A and Parkes, RW and du Bois, R and Turner-Warwick, M}, title = {Radiographic progression of asbestosis: preliminary report.}, journal = {Annals of the New York Academy of Sciences}, volume = {330}, number = {}, pages = {147-156}, doi = {10.1111/j.1749-6632.1979.tb18715.x}, pmid = {316663}, issn = {0077-8923}, mesh = {Antibodies, Antinuclear/analysis ; Asbestosis/*diagnostic imaging/immunology/mortality ; Epidemiologic Methods ; Humans ; London ; Lung Neoplasms/mortality ; Mesothelioma/mortality ; Middle Aged ; Occupational Diseases/mortality ; Peritoneal Neoplasms/mortality ; Pleural Neoplasms/mortality ; Radiography ; Time Factors ; }, abstract = {In a collaborative study with the Pneumoconiosis Medical Panel, 232 asbestos workers were seen between 1967 and 1975. During this time, 50 of the 232 (21.5%) workers dies, 33 (13.8%) from respiratory disease probably related to asbestos exposure [10 (4.3%) pleural mesothelioma, three (1.3%) peritoneal mesothelioma, 10 (4.3%) asbestosis, 10 (4.3%) carcinoma of the lung]. Of the 182 survirors, 119 were recalled for other studies, and follow-up data were obtained as additional information at the same time, over a 1--7 year period. Paired radiographs were read, and 21 patients (17.6%) had worsened. As expected, the frequency of progression increased with a longer follow-up time, so that about one third of the subjects displayed progression after a minimum follow-up of 6 years. Ten of 73 patients (13.6%) had progressed in 3 years or less and may be defined as rapid progressors. No particular clinical feature distinguished clearly between progressors and nonprogressors, but there was a trend toward a greater frequency and higher titer of ANA among the progressors in this group. There was also a higher frequency of progression in those who were initially classified radiographically as 1/1 of 1/2 than in those with other initial radiographic appearances. This pilot study is now forming the basis for a larger, longer-term comprehensive survey.}, } @article {pmid294225, year = {1979}, author = {Selikoff, IJ and Hammond, EC and Seidman, H}, title = {Mortality experience of insulation workers in the United States and Canada, 1943--1976.}, journal = {Annals of the New York Academy of Sciences}, volume = {330}, number = {}, pages = {91-116}, doi = {10.1111/j.1749-6632.1979.tb18711.x}, pmid = {294225}, issn = {0077-8923}, mesh = {Adolescent ; Adult ; Aged ; Asbestos/*adverse effects ; Asbestosis/mortality ; Canada ; Epidemiologic Methods ; Gastrointestinal Neoplasms/mortality ; Humans ; Lung Neoplasms/mortality ; Male ; Mesothelioma/mortality ; Middle Aged ; Neoplasms/mortality ; Neoplasms, Multiple Primary/mortality ; Occupational Diseases/etiology/*mortality ; United States ; }, } @article {pmid294224, year = {1979}, author = {Davis, JM}, title = {The use of animal models for studies on asbestos bioeffects.}, journal = {Annals of the New York Academy of Sciences}, volume = {330}, number = {}, pages = {795-798}, doi = {10.1111/j.1749-6632.1979.tb18785.x}, pmid = {294224}, issn = {0077-8923}, mesh = {Animals ; Asbestos/*adverse effects ; Asbestosis/*etiology ; Cats ; Cricetinae ; Disease Models, Animal ; Guinea Pigs ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Mice ; Neoplasms, Experimental/etiology ; Particle Size ; Pulmonary Fibrosis/etiology ; Rabbits ; Rats ; }, } @article {pmid294223, year = {1979}, author = {Frank, AL}, title = {Public health significance of smoking-asbestos interactions.}, journal = {Annals of the New York Academy of Sciences}, volume = {330}, number = {}, pages = {791-794}, doi = {10.1111/j.1749-6632.1979.tb18784.x}, pmid = {294223}, issn = {0077-8923}, mesh = {Asbestos/*adverse effects ; Asbestosis/mortality ; Epidemiologic Methods ; Humans ; Lung Neoplasms/*etiology/mortality ; Male ; Mesothelioma/mortality ; Neoplasms/mortality ; Occupational Diseases/*mortality ; Public Health ; Smoking/*complications ; United States ; }, } @article {pmid294215, year = {1979}, author = {Pooley, FD and Clark, N}, title = {Fiber dimensions and aspect ratio of crocidolite, chrysotile and amosite particles detected in lung tissue specimens.}, journal = {Annals of the New York Academy of Sciences}, volume = {330}, number = {}, pages = {711-716}, doi = {10.1111/j.1749-6632.1979.tb18775.x}, pmid = {294215}, issn = {0077-8923}, mesh = {Asbestos/*isolation & purification ; Asbestosis/*metabolism ; Humans ; Lung/*analysis ; Mesothelioma/*analysis ; Minerals/isolation & purification ; Particle Size ; }, abstract = {Chrysotile, amosite and crocidolite fibers detected in autopsy tissue specimens from cases of mesothelioma and controls have been characterized by particle length, diameter and aspect ratio using a transmission electron microscope. The pooled information from such specimens reveals that the fibers of each mineral type detected in biological material have very different physical characteristics although in all samples fibers less than 5 microns in length are predominant by number while fibers over 25 microns in length are found very infrequently. Chrysotile fibers on average appear as the shortest fibers with the most fine diameter distribution, amosite fibers are on average the longest with the most coarse diameter distribution, crocidolite fibers on average have dimensions which are intermediate between both chrysotile and amosite. The percentage number of fibers of chrysotile, amosite and crocidolite detected with an aspect ratio less than or equal to 10 were 31.7%, 24.2% and 18.5% respectively.}, } @article {pmid294211, year = {1979}, author = {Nicholson, WJ and Swoszowski, EJ and Rohl, AN and Todaro, JD and Adams, A}, title = {Asbestos contamination in United States schools from use of asbestos surfacing materials.}, journal = {Annals of the New York Academy of Sciences}, volume = {330}, number = {}, pages = {587-596}, doi = {10.1111/j.1749-6632.1979.tb18763.x}, pmid = {294211}, issn = {0077-8923}, mesh = {Air Pollutants/*analysis ; Asbestos/adverse effects/*analysis ; Asbestosis/etiology ; Humans ; Mesothelioma/etiology ; *Schools ; United States ; }, } @article {pmid294204, year = {1979}, author = {Newhouse, ML and Berry, G}, title = {Patterns of mortality in asbestos factory workers in London.}, journal = {Annals of the New York Academy of Sciences}, volume = {330}, number = {}, pages = {53-60}, doi = {10.1111/j.1749-6632.1979.tb18709.x}, pmid = {294204}, issn = {0077-8923}, mesh = {Asbestos/*adverse effects ; Asbestosis/mortality ; Epidemiologic Methods ; Female ; Gastrointestinal Neoplasms/mortality ; Humans ; London ; Lung Neoplasms/mortality ; Male ; Mesothelioma/mortality ; Neoplasms/mortality ; Occupational Diseases/*mortality ; Pleural Neoplasms/mortality ; Smoking ; }, } @article {pmid294197, year = {1979}, author = {Planteydt, HT}, title = {Netherlands mesothelioma register.}, journal = {Annals of the New York Academy of Sciences}, volume = {330}, number = {}, pages = {467-471}, doi = {10.1111/j.1749-6632.1979.tb18748.x}, pmid = {294197}, issn = {0077-8923}, mesh = {Aged ; Asbestos/*adverse effects ; Epidemiologic Methods ; Female ; Humans ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Netherlands ; Occupational Diseases/*epidemiology ; Peritoneal Neoplasms/*epidemiology ; Pleural Neoplasms/*epidemiology ; *Registries ; }, } @article {pmid294196, year = {1979}, author = {Bignon, J and Sebastien, P and Di Menza, L and Payan, H}, title = {French mesothelioma register.}, journal = {Annals of the New York Academy of Sciences}, volume = {330}, number = {}, pages = {455-466}, doi = {10.1111/j.1749-6632.1979.tb18747.x}, pmid = {294196}, issn = {0077-8923}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Epidemiologic Methods ; Female ; France ; Humans ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Diseases/*epidemiology ; Peritoneal Neoplasms/*epidemiology/etiology ; Pleural Neoplasms/*epidemiology/etiology ; *Registries ; Surveys and Questionnaires ; }, abstract = {A total of 197 definite cases of mesothelioma (mainly of the pleura) have been reported by pathologists to the French Mesothelioma Register for the period 1965--78. A moderate linear increase in the annual incidence of mesothelioma cases since 1965 was noted. In men and women over the ages of 47 and 41 years, respectively, the annual death rate was higher in those with mesothelioma than in those of the general population. The proportions of mesothelioma patients who had experienced occupational, para-occupational, and unknown asbestos exposures were 77%, 3%, and 20% respectively. The number of cases reported to the register is obviously an underestimate of the true number of mesothelima cases in France, because such cases are not reported to the register systematically. Mesothelioma registers cannot provide information about dose-response relationships; however, with good management of the register, such relationships could be obtained, since a good assessment of dose can be accomplished by biologic monitoring.}, } @article {pmid294195, year = {1979}, author = {McDonald, AD}, title = {Mesothelioma registries in identifying asbestos hazards.}, journal = {Annals of the New York Academy of Sciences}, volume = {330}, number = {}, pages = {441-454}, doi = {10.1111/j.1749-6632.1979.tb18746.x}, pmid = {294195}, issn = {0077-8923}, mesh = {Adolescent ; Adult ; Aged ; Asbestos/*adverse effects ; Epidemiologic Methods ; Female ; Housing ; Humans ; Male ; Mesothelioma/epidemiology/*etiology ; Middle Aged ; Mining ; Occupational Diseases/*epidemiology ; *Registries ; }, } @article {pmid294193, year = {1979}, author = {Bariş, YI and Artvinli, M and Sahin, AA}, title = {Environmental mesothelioma in Turkey.}, journal = {Annals of the New York Academy of Sciences}, volume = {330}, number = {}, pages = {423-432}, doi = {10.1111/j.1749-6632.1979.tb18744.x}, pmid = {294193}, issn = {0077-8923}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Epidemiologic Methods ; Female ; Humans ; Male ; Mesothelioma/*etiology/genetics/mortality ; Middle Aged ; Pleural Diseases/etiology ; Pleural Neoplasms/*etiology/genetics/mortality ; Pleurisy/etiology ; Turkey ; }, } @article {pmid294189, year = {1979}, author = {Wright, GW}, title = {What to do about the asbestos currently in ships and industry?.}, journal = {Annals of the New York Academy of Sciences}, volume = {330}, number = {}, pages = {383-386}, doi = {10.1111/j.1749-6632.1979.tb18740.x}, pmid = {294189}, issn = {0077-8923}, mesh = {Asbestos/*adverse effects ; Humans ; Mesothelioma/prevention & control ; Occupational Diseases/*prevention & control ; Occupational Medicine ; *Ships ; }, } @article {pmid294184, year = {1979}, author = {de Lajartre, M and de Lajartre, AY}, title = {Mesothelioma on the coast of Brittany, France.}, journal = {Annals of the New York Academy of Sciences}, volume = {330}, number = {}, pages = {323-332}, doi = {10.1111/j.1749-6632.1979.tb18735.x}, pmid = {294184}, issn = {0077-8923}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Epidemiologic Methods ; Female ; France ; Humans ; Male ; Mesothelioma/diagnosis/*epidemiology/etiology ; Middle Aged ; Occupational Diseases/*epidemiology ; Pleural Neoplasms/diagnosis/*epidemiology/etiology ; *Ships ; Time Factors ; }, } @article {pmid294183, year = {1979}, author = {Stumphius, J}, title = {Mesothelioma incidence in a Dutch shipyard.}, journal = {Annals of the New York Academy of Sciences}, volume = {330}, number = {}, pages = {317-322}, doi = {10.1111/j.1749-6632.1979.tb18734.x}, pmid = {294183}, issn = {0077-8923}, mesh = {Asbestos/*adverse effects ; Epidemiologic Methods ; Humans ; Mesothelioma/*epidemiology/etiology ; Netherlands ; Occupational Diseases/*epidemiology ; *Ships ; }, abstract = {On Walcheren Island (the Netherlands), 25 cases of mesothelioma were diagnosed from 1962 to 1968. In 22 cases, there had been an occupational association with Royal Schelde, the shipyard in Vlissingen. A relationship with exposure to asbestos, frequently used in shipbuilding in the past, could be demonstrated. Further observations showed the expected increase of mesothelioma cases in Royal Schelde workers. In 1974, the number of cases totaled 42; in 1978, the number rose to 57. In addition, five more recent cases have not yet been confirmed histologically, but the clinical symptoms are unmistakable. In seven of 12 mesothelioma cases on Walcheren Island that had no association with Royal Schelde, asbestos exposure in the occupational history could also be traced. Finally, a few facts are mentioned about the recent Dutch Asbestos Act.}, } @article {pmid294180, year = {1979}, author = {Selikoff, IJ and Lilis, R and Nicholson, WJ}, title = {Asbestos disease in United States shipyards.}, journal = {Annals of the New York Academy of Sciences}, volume = {330}, number = {}, pages = {295-311}, doi = {10.1111/j.1749-6632.1979.tb18732.x}, pmid = {294180}, issn = {0077-8923}, mesh = {Adult ; Asbestos/*adverse effects ; Asbestosis/*mortality ; Epidemiologic Methods ; Female ; Humans ; Lung Neoplasms/mortality ; Male ; Mesothelioma/mortality ; Middle Aged ; Occupational Diseases/mortality ; Risk ; *Ships ; United States ; }, } @article {pmid294178, year = {1979}, author = {Sheers, G}, title = {Asbestos-associated disease in employees of Devonport Dockyard.}, journal = {Annals of the New York Academy of Sciences}, volume = {330}, number = {}, pages = {281-287}, doi = {10.1111/j.1749-6632.1979.tb18730.x}, pmid = {294178}, issn = {0077-8923}, mesh = {Adult ; Asbestos/*adverse effects ; Asbestosis/epidemiology ; England ; Epidemiologic Methods ; Humans ; Lung Neoplasms/etiology ; Male ; Mesothelioma/etiology ; Middle Aged ; Occupational Diseases/*epidemiology ; Pleural Diseases/etiology ; Pulmonary Fibrosis/etiology ; *Ships ; Smoking/complications ; }, } @article {pmid294170, year = {1979}, author = {Robock, K}, title = {Based on available data, can we project an acceptable standard for industrial use of asbestos? Absolutely.}, journal = {Annals of the New York Academy of Sciences}, volume = {330}, number = {}, pages = {205-210}, doi = {10.1111/j.1749-6632.1979.tb18721.x}, pmid = {294170}, issn = {0077-8923}, mesh = {Animals ; Asbestos/*adverse effects ; Humans ; Maximum Allowable Concentration ; Mesothelioma/prevention & control ; Neoplasms, Experimental/etiology ; Occupational Diseases/*prevention & control ; Risk ; }, } @article {pmid294169, year = {1979}, author = {Peto, J}, title = {Dose-response relationships for asbestos-related disease: implications for hygiene standards. Part II. Mortality.}, journal = {Annals of the New York Academy of Sciences}, volume = {330}, number = {}, pages = {195-203}, doi = {10.1111/j.1749-6632.1979.tb18720.x}, pmid = {294169}, issn = {0077-8923}, mesh = {Adult ; Age Factors ; Aged ; Asbestos/*adverse effects ; Environmental Exposure ; Epidemiologic Methods ; Humans ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; Middle Aged ; Occupational Diseases/*mortality/prevention & control ; Peritoneal Neoplasms/mortality ; Pleural Neoplasms/mortality ; Statistics as Topic ; Time Factors ; }, } @article {pmid294163, year = {1979}, author = {Lilis, R and Daum, S and Anderson, H and Sirota, M and Andrews, G and Selikoff, IJ}, title = {Asbestos disease in maintenance workers of the chemical industry.}, journal = {Annals of the New York Academy of Sciences}, volume = {330}, number = {}, pages = {127-135}, doi = {10.1111/j.1749-6632.1979.tb18713.x}, pmid = {294163}, issn = {0077-8923}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Asbestosis/diagnosis/epidemiology/*etiology ; *Chemical Industry ; Epidemiologic Methods ; Female ; Humans ; Male ; Middle Aged ; New Jersey ; Pleural Diseases/etiology ; Pulmonary Fibrosis/etiology ; Respiratory Function Tests ; }, abstract = {In several large groups of workers employed in chemical plants, chest x-ray abnormalities (small irregular opacities and/or pleural changes) of the type known to be induced by asbestos were found in a proportion of those examined. A cross-sectional study of maintenance workers in a large chemical plant was undertaken to evaluate the prevalence of asbestosis; 185 workers were examined. Radiologic evidence of parenchymal interstitial fibrosis was found in 24% of those examined; in 10% of workers, parenchymal fibrosis was the only abnormality. Pleural fibrosis and/or calcification was found in the absence of parenchymal fibrosis in 14% of cases; in another 14% of workers, both parenchymal and pleural abnormalities were detected. The prevalence was significantly higher in those employed 20 or more years. Pleural abnormalities were more prevalent than were parenchymal changes. The increased risk of lung cancer and mesothelioma remains to be studied.}, } @article {pmid294162, year = {1979}, author = {Henderson, VL and Enterline, PE}, title = {Asbestos exposure: factors associated with excess cancer and respiratory disease mortality.}, journal = {Annals of the New York Academy of Sciences}, volume = {330}, number = {}, pages = {117-126}, doi = {10.1111/j.1749-6632.1979.tb18712.x}, pmid = {294162}, issn = {0077-8923}, mesh = {Aged ; Asbestos/*adverse effects ; Asbestosis/*mortality ; Epidemiologic Methods ; Humans ; Male ; Mesothelioma/mortality ; Middle Aged ; Occupational Diseases/etiology/*mortality ; Pulmonary Fibrosis/mortality ; Respiratory Tract Neoplasms/*mortality ; Time Factors ; United States ; }, abstract = {A cohort of 1075 men who completed their working lifetimes with an asbestos company, worked at a facility in the United States, and retired with a company pension during the period 1941--67 was updated for deaths through 1973. The average length of employment was 25 years, and all had been exposed to asbestos dust. Respiratory cancer and pneumoconiosis-pulmonary fibrosis mortalities were examined in relation to cumulative dust exposure and to other factors after taking into account cumulative dust exposure. Men who worked in the production of asbestos cement pipe exhibited a higher risk of respiratory cancer, as did men with some crocidolite asbestos exposure. Because these two groups overlap, we could not be certain that crocidolite asbestos was responsible for the increased risk. Men working in general plant maintenance displayed a striking lack of deaths due to pneumoconiosis-pulmonary fibrosis, as compared with production workers and with maintenance personnel assigned to specific departments. Five mesothelioma deaths were observed at age 65 and over. Three of these deaths occurred during the period 1970--3.}, } @article {pmid294161, year = {1979}, author = {Nicholson, WJ and Selikoff, IJ and Seidman, H and Lilis, R and Formby, P}, title = {Long-term mortality experience of chrysotile miners and millers in Thetford Mines, Quebec.}, journal = {Annals of the New York Academy of Sciences}, volume = {330}, number = {}, pages = {11-21}, doi = {10.1111/j.1749-6632.1979.tb18705.x}, pmid = {294161}, issn = {0077-8923}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Asbestosis/mortality ; Epidemiologic Methods ; Humans ; Lung Neoplasms/mortality ; Male ; Mesothelioma/mortality ; Middle Aged ; *Mining ; Neoplasms/mortality ; Occupational Diseases/etiology/*mortality ; Quebec ; Risk ; }, abstract = {Among a cohort of 544 men with at least 20 years of employment in chrysotile mining and milling at Thetford Mines, Canada, 16% of the deaths were from lung cancer and 15% from asbestosis. The excess over expected deaths from these causes account for 43 of 178 deaths in the group. The risk of death of asbestosis, at equal times fron onset of exposure, is very similar in miners and millers, factory workmen and insulators. The ratio of observed to expected deaths from lung cancer is similar in the miners and millers and factory workers, but higher in insulators. The risk of death of mesothelioma in miners and millers is decidedly less than the other two groups. The exact causes of the reduced risk in this category are not yet completely clarified.}, } @article {pmid294160, year = {1979}, author = {McDonald, JC and Liddell, FD}, title = {Mortality in Canadian miners and millers exposed to chrysotile.}, journal = {Annals of the New York Academy of Sciences}, volume = {330}, number = {}, pages = {1-9}, doi = {10.1111/j.1749-6632.1979.tb18704.x}, pmid = {294160}, issn = {0077-8923}, mesh = {Aged ; Asbestos/*adverse effects ; Canada ; Epidemiologic Methods ; Female ; Humans ; Male ; Mesothelioma/mortality ; Middle Aged ; *Mining ; Occupational Diseases/etiology/*mortality ; Respiratory Tract Neoplasms/mortality ; Risk ; Smoking/complications ; Time Factors ; }, } @article {pmid230775, year = {1979}, author = {Heppleston, AG}, title = {Silica and asbestos: contrasts in tissue response.}, journal = {Annals of the New York Academy of Sciences}, volume = {330}, number = {}, pages = {725-744}, doi = {10.1111/j.1749-6632.1979.tb18777.x}, pmid = {230775}, issn = {0077-8923}, mesh = {Animals ; Asbestos/*adverse effects ; Asbestosis/*pathology ; Cell Survival/drug effects ; Chick Embryo ; Fibroblasts/metabolism ; Guinea Pigs ; Humans ; Hydroxyproline/biosynthesis ; Lipid Metabolism ; Lung/*drug effects ; Lung Neoplasms/etiology ; Macrophages/drug effects ; Mesothelioma/etiology ; Pulmonary Fibrosis/pathology ; Rats ; Silicon Dioxide/*adverse effects ; Silicosis/*pathology ; }, } @article {pmid749422, year = {1978}, author = {Neuberger, M and Gründorfer, W and Haider, M and Königshofer, R and Müller, HW and Raber, A and Riedmüller, G and Schwaighofer, B}, title = {[Endemic pleural plaques and environmental factors (author's transl)].}, journal = {Zentralblatt fur Bakteriologie, Parasitenkunde, Infektionskrankheiten und Hygiene. Erste Abteilung Originale. Reihe B: Hygiene, Betriebshygiene, praventive Medizin}, volume = {167}, number = {5-6}, pages = {391-404}, pmid = {749422}, mesh = {Asbestos/adverse effects ; Asbestosis/diagnosis ; Austria ; Environmental Pollution ; Humans ; Occupational Diseases ; Pleural Diseases/diagnostic imaging/*epidemiology ; Radiography ; }, abstract = {In an agricultural town in Burgenland (Austria) we found an increased prevalence of pleural plaques. These calcifying thickenings of the pleura are related to minimal asbestos exposure such as is mesothelioma, but they cannot be regarded as a precancerosis. The increased occurrence of pleural plaques in this town of nearly 3500 inhabitants (in which during 1916 to 1945 asbestos was mined) we first found at the chest x-ray archives of a pulmologic hospital, then by mass radiography and blind comparison with control groups. A photofluoroscopy of 300 persons yielded 16 cases with definite pleural plaques (5.3%) among which were 4 cases with suspected asbestosis and another 14 cases with uncertain pleural plaques (4.7%). The 600 control persons showed no such radiological changes. Interviews wich persons detected for pleural plaques at mass radiography gave no indication that they had occupational asbestos exposure. But asbestos was detected in the soil of vineyards and in the dust of the houses. Asbestos was also detectable in the atmospheric dust by x-ray diffraction and scanning electron microscopic techniques.}, } @article {pmid739508, year = {1978}, author = {Whitwell, F}, title = {Problems in the pathology of disease caused by asbestos.}, journal = {Journal of the Royal Society of Medicine}, volume = {71}, number = {12}, pages = {919-922}, pmid = {739508}, issn = {0141-0768}, mesh = {Asbestosis/*pathology ; Autopsy ; Humans ; Lung/pathology ; Lung Neoplasms/pathology ; Mesothelioma/pathology ; Pleural Neoplasms/pathology ; }, } @article {pmid739507, year = {1978}, author = {Galloway, RW}, title = {Awkward mediolegal problems in asbestos-induced disease. Problem radiographs.}, journal = {Journal of the Royal Society of Medicine}, volume = {71}, number = {12}, pages = {916-919}, doi = {10.1177/014107687807101215}, pmid = {739507}, issn = {0141-0768}, mesh = {Asbestosis/*diagnostic imaging ; Diagnosis, Differential ; Female ; Humans ; Lung Neoplasms/diagnostic imaging ; Male ; Mesothelioma/diagnostic imaging ; Middle Aged ; Pleural Neoplasms/diagnostic imaging ; Pulmonary Fibrosis/diagnostic imaging ; Radiography ; }, } @article {pmid739506, year = {1978}, author = {Elmes, PC}, title = {Risk factors in asbestos exposure.}, journal = {Journal of the Royal Society of Medicine}, volume = {71}, number = {12}, pages = {914-916}, pmid = {739506}, issn = {0141-0768}, mesh = {Asbestos/*adverse effects ; Asbestosis/etiology ; Humans ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Occupational Diseases/etiology ; Risk ; Time Factors ; }, } @article {pmid725038, year = {1978}, author = {Banner, MP and Gohel, VK}, title = {Peritoneal mesothelioma.}, journal = {Radiology}, volume = {129}, number = {3}, pages = {637-640}, doi = {10.1148/129.3.637}, pmid = {725038}, issn = {0033-8419}, mesh = {Adult ; Aged ; Diagnosis, Differential ; Female ; Humans ; Male ; Mesothelioma/*diagnostic imaging/pathology ; Middle Aged ; Peritoneal Neoplasms/*diagnostic imaging/pathology ; Radiography ; }, abstract = {Five cases of malignant peritoneal mesothelioma are reported. Its radiographic manifestations consisted of a desmoplastic mesenteric process with or without a localized mass displacing gastrointestinal structures. Appreciation of the nature of this tumor permits pathologic-radiologic correlation and an understanding of the radiographic changes. Though numerous conditions may produce similar findings, combining a history of asbestos exposure or chest radiograph findings of asbestosis with gastrointestinal findings of desomplasia should narrow the diagnostic possibilities.}, } @article {pmid318525, year = {1978}, author = {Wehner, AP and Dagle, GE and Cannon, WC and Buschbom, RL}, title = {Asbestos cement dust inhalation by hamsters.}, journal = {Environmental research}, volume = {17}, number = {3}, pages = {367-389}, doi = {10.1016/0013-9351(78)90041-5}, pmid = {318525}, issn = {0013-9351}, mesh = {Aerosols ; Animals ; Asbestos/*toxicity ; Body Weight ; Cricetinae ; *Dust ; Environmental Exposure ; Lung/drug effects/*pathology ; Male ; Particle Size ; Pulmonary Fibrosis/*etiology ; }, abstract = {Two groups of 96 male Syrian golden hamsters were exposed to respirable asbestos cement aerosol at concentrations of approximately 1 and approximately 10 micrograms/liter, respectively, 3 hours/day, 5 days/week. Average fiber counts ranged from 5 to about 120 fibers/cm3. Each group was randomly divided into six subgroups of 16 animals. The first subgroup was sacrificed after 3 months of exposure, the second after 6 months, and the third after 15 months. The fourth subgroup was withdrawn from exposure after 3 months, observed for an additional 3 months, and then sacrificed. The fifth and sixth subgroups were withdrawn after 3 and 6 months of exposure, respectively, and maintained for observation up to the 15-month exposure point of the third subgroup at which time all surviving animals were sacrificed. All other experimental procedures were similar to those delineated in a previous publication describing the development of an animal model, techniques, and an exposure system for asbestos cement dust inhalation (A. P. Wehner, G. E. Dagle, and W. C. Cannon, 1978, Environ. Res. 16, 393-407). The asbestos cement exposures had no significant effect on body weight and mortality of the animals. Higher aerosol concentration and longer exposure times increased the number of macrophages and ferruginous bodies found in the lungs of the exposed animals. Recovery periods had no effect on the incidence of macrophages and ferruginous bodies. The incidence of very slight to slight fibrosis in the animals sacrificed after 15 months of exposure shows a significant (P less than 0.01) trend when the untreated control group and the 1 and 10 microgram/liter dose level groups are compared, indicating a dose-response relationship. Development of minimal fibrosis continued in animals withdrawn from exposure. No primary carcinomas of the lung and respiratory tract and no mesotheliomas were found.}, } @article {pmid233818, year = {1978}, author = {McDonald, AD and McDonald, JC}, title = {Mesothelioma after crocidolite exposure during gas mask manufacture.}, journal = {Environmental research}, volume = {17}, number = {3}, pages = {340-346}, doi = {10.1016/0013-9351(78)90038-5}, pmid = {233818}, issn = {0013-9351}, mesh = {Asbestos/*toxicity ; Asbestos, Crocidolite ; Asbestos, Serpentine ; Canada ; *Environmental Exposure ; Female ; Humans ; Industry ; Lung Neoplasms/*etiology ; Male ; Mesothelioma/*etiology ; Mining ; Respiratory Protective Devices ; }, abstract = {Of 199 persons employed in the manufacture and handling of Canadian military gas mask canisters containing pure crocidolite, 1939 to 1942, by the end of 1975, 56 had died, 120 were still alive, and 23 could not be traced. Nine (16%) of the deaths were probably due to malignant mesothelioma, six involving the peritoneum. The risk of mesothelioma after crocidolite exposure appears to be many times greater than that after chrysotile.}, } @article {pmid715745, year = {1978}, author = {Melbostad, E}, title = {[Asbestos exposure---asbestos damage. A brief review].}, journal = {Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke}, volume = {98}, number = {31}, pages = {1563-1564}, pmid = {715745}, issn = {0029-2001}, mesh = {Asbestos/*adverse effects ; Asbestosis/etiology ; Environmental Exposure ; Humans ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Pleural Diseases/etiology ; Smoking/complications ; Time Factors ; }, } @article {pmid710281, year = {1978}, author = {Eck, H and Berg-Schlosser, V}, title = {[On the aetiology of malignant pericardial mesothelioma (author's transl)].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {103}, number = {44}, pages = {1751-1753}, doi = {10.1055/s-0028-1129337}, pmid = {710281}, issn = {0012-0472}, mesh = {Aged ; Asbestosis/complications ; Autopsy ; Female ; Heart Neoplasms/*etiology/pathology ; Humans ; Male ; Mesothelioma/*etiology/pathology ; Middle Aged ; *Pericardium ; }, abstract = {Two cases of malignant pericardial mesothelioma are described. Morphologically they corresponded to the epithelial or fibrous type, respectively. In one patient, an old-metal dealer, an increased number of asbestos bodies were found in the lung parenchyma and phase-microscopy demonstrated increased asbestos needles in the lung parenchyma. Since, beyond a certain fibre size, asbestos can induce bronchial carcinoma as well as pleural or peritoneal mesothelioma, it is likely that the pericardial mesothelioma had a similar aetiology.}, } @article {pmid741520, year = {1978}, author = {Bianchi, C and Grandi, G and Di Bonito, L}, title = {Diffuse pleural mesothelioma in Trieste. A survey based on autopsy cases.}, journal = {Tumori}, volume = {64}, number = {6}, pages = {565-570}, doi = {10.1177/030089167806400602}, pmid = {741520}, issn = {0300-8916}, mesh = {Aged ; Asbestos/adverse effects ; Epidemiologic Methods ; Female ; Humans ; Italy ; Male ; Mesothelioma/etiology/*mortality ; Middle Aged ; Occupational Diseases/etiology ; Pleural Neoplasms/etiology/*mortality ; }, abstract = {Records of necropsies performed at the Institute of Pathological Anatomy and Histology of the University of Trieste during the period December 1 1971-December 31 1977 have been reviewed. Cases with a necropsy diagnosis of pleural tumor or lung sarcoma were reexamined. Twenty-six cases were accepted as definite diffuse pleural mesothelioma. Occupational history was indicative of asbestos exposure in 22 cases, with 12 patients having worked in shipyards. The high incidence of diffuse pleural mesothelioma in the Province of Trieste is emphasized.}, } @article {pmid740605, year = {1978}, author = {Lee, WR}, title = {Advances in occupational health.}, journal = {The Practitioner}, volume = {221}, number = {1324}, pages = {581-585}, pmid = {740605}, issn = {0032-6518}, mesh = {Air Conditioning ; Alveolitis, Extrinsic Allergic/etiology ; Asbestos/adverse effects ; Asbestosis/etiology ; Carcinogens ; Humans ; Legislation as Topic ; Mesothelioma/etiology ; Occupational Diseases/*prevention & control ; Radiation Protection/standards ; United Kingdom ; }, } @article {pmid707524, year = {1978}, author = {Hasan, FM and Nash, G and Kazemi, H}, title = {Asbestos exposure and related neoplasia. The 28 year experience of a major urban hospital.}, journal = {The American journal of medicine}, volume = {65}, number = {4}, pages = {649-654}, doi = {10.1016/0002-9343(78)90853-7}, pmid = {707524}, issn = {0002-9343}, mesh = {Adenocarcinoma/complications ; Adult ; Aged ; Asbestos/*adverse effects ; Asbestosis/complications/diagnosis ; Humans ; Lung Neoplasms/complications/*etiology ; Mesothelioma/complications/*etiology ; Middle Aged ; Occupational Diseases/*etiology ; Occupations ; }, abstract = {In a retrospective study of 49 cases of asbestosis, a steady increase in the frequency of diagnosis of asbestosis and asbestos-related neoplasia is documented from a major urban hospital since 1960. Although in the majority of cases the subjects were exposed to asbestos in a neighboring shipyard, in 20 per cent of the cases, asbestos exposure was in industries not related to shipbuilding, reflecting its widespread use. This selective population of patients with asbestosis more often than not had an associated neoplasm. The most likely accompanying tumor was pleural mesothelioma, and among cell types of lung cancer, adenocarcinoma was notably frequent.}, } @article {pmid359267, year = {1978}, author = {Aisner, J and Wiernik, PH}, title = {Malignant mesothelioma. Current status and future prospects.}, journal = {Chest}, volume = {74}, number = {4}, pages = {438-444}, doi = {10.1378/chest.74.4.438}, pmid = {359267}, issn = {0012-3692}, mesh = {Air Pollutants, Occupational/adverse effects ; Animals ; Antineoplastic Agents/therapeutic use ; Asbestos/adverse effects ; Carcinogens, Environmental ; Drug Evaluation ; Drug Therapy, Combination ; Forecasting ; Humans ; *Mesothelioma/diagnosis/mortality/therapy ; *Pleural Neoplasms/diagnosis/mortality/therapy ; Prognosis ; Radioisotopes/therapeutic use ; Smoking/complications ; Time Factors ; }, } @article {pmid309354, year = {1978}, author = {Fischbein, A and Suzuki, Y and Selikoff, IJ and Bekesi, JG}, title = {Unexpected longevity of a patient with malignant pleural mesothelioma: report of a case.}, journal = {Cancer}, volume = {42}, number = {4}, pages = {1999-2004}, doi = {10.1002/1097-0142(197810)42:4<1999::aid-cncr2820420447>3.0.co;2-y}, pmid = {309354}, issn = {0008-543X}, mesh = {B-Lymphocytes/immunology ; Humans ; Lymphocyte Activation ; Male ; Mesothelioma/diagnosis/immunology/*pathology ; Middle Aged ; Mitogens/pharmacology ; Pleural Neoplasms/diagnosis/immunology/*pathology ; T-Lymphocytes/immunology ; Time Factors ; }, abstract = {A 53-year-old male with untreated malignant pleural mesothelioma and with seven years survival time since the appearance of clinical symptoms is reported. Histopathological and immunological findings were at variance with those usually seen with mesothelioma. Both lymphocyte surface markers and lymphocyte function values were found to be within normal range; in contrast, in eleven mesothelioma patients who progressed and died, both numerical and functional defects in T and B lymphocytes were seen. There was potential for neighborhood asbestos exposure.}, } @article {pmid81715, year = {1978}, author = {Chahinian, AP and Suzuki, Y and Mandel, EM and Holland, JF}, title = {Diffuse pulmonary malignant mesothelioma: response to doxorubicin and 5-azacytidine.}, journal = {Cancer}, volume = {42}, number = {4}, pages = {1687-1691}, doi = {10.1002/1097-0142(197810)42:4<1687::aid-cncr2820420405>3.0.co;2-n}, pmid = {81715}, issn = {0008-543X}, mesh = {Azacitidine/*administration & dosage ; Doxorubicin/*administration & dosage ; Drug Therapy, Combination ; Humans ; Infusions, Parenteral ; Lung Neoplasms/*drug therapy/pathology ; Male ; Mesothelioma/*drug therapy/pathology ; Middle Aged ; Remission, Spontaneous ; }, abstract = {A 46-year-old patient who developed a right pleural mesothelioma 18 years after asbestos exposure was found to have diffuse reticular nodular infiltrates in both lungs. Lung biopsy by fiberoptic bronchoscopy revealed alveolar and interstitial spread of the neoplastic cells. A dramatic clinical and radiologic response occurred after treatment with a combination of doxorubicin (Adriamycin) and 5-Azacytidine.}, } @article {pmid79885, year = {1978}, author = {McCullagh, SF}, title = {Non-occupational exposure to asbestos and malignant mesothelioma.}, journal = {Lancet (London, England)}, volume = {2}, number = {8088}, pages = {521-522}, doi = {10.1016/s0140-6736(78)92240-7}, pmid = {79885}, issn = {0140-6736}, mesh = {Asbestos/*adverse effects ; Environmental Exposure ; Humans ; Mesothelioma/*etiology ; }, } @article {pmid357181, year = {1978}, author = {Anderson, HA and Selikoff, IJ}, title = {Pleural reactions to environmental agents.}, journal = {Federation proceedings}, volume = {37}, number = {11}, pages = {2496-2500}, pmid = {357181}, issn = {0014-9446}, mesh = {Air Pollutants/*adverse effects ; Asbestos/adverse effects ; Humans ; Occupational Diseases/diagnostic imaging ; Pleural Diseases/diagnostic imaging/*etiology ; Radiography ; }, abstract = {In the past, pleural disease has been uncommon, generally limited to infection derived from underlying pulmonary involvement or the result of local neoplastic invasion or hematogenous metastases. The deep, protected location of the lung's mesothelial surface provides insufficient defense against environmentally derived very fine biologically active inorganic particles, and a new set of abnormalities--pleural plaques, fibrosis, unique calcification, malignancy (mesothelioma), benign asbestotic effusion--have introduced problems of pathogenesis, diagnosis, management, and therapy. These changes are becoming frequent among individuals who were exposed to asbestos more than 20 years ago. Occupational exposure (direct and indirect), and in some cases environmental exposure (household contacts of asbestos-exposed workers and factory neighborhood residents), have been associated with higher prevalence of radiographically evident pleural abnormalities. What effects such changes will have on morbidity and mortality rates is incompletely understood.}, } @article {pmid698613, year = {1978}, author = {Jefferys, DB and Vale, JA}, title = {Malignant mesothelioma and gas-mask assemblers.}, journal = {British medical journal}, volume = {2}, number = {6137}, pages = {607}, pmid = {698613}, issn = {0007-1447}, mesh = {Aged ; Asbestos/*adverse effects ; Female ; Humans ; Male ; Mesothelioma/*etiology ; Middle Aged ; Occupational Diseases/*chemically induced ; Pleural Neoplasms ; Respiratory Protective Devices ; }, } @article {pmid715610, year = {1978}, author = {Cochrane, JC and Webster, I}, title = {Mesothelioma in relation to asbestos fibre exposure. A review of 70 serial cases.}, journal = {South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde}, volume = {54}, number = {7}, pages = {279-281}, pmid = {715610}, issn = {0256-9574}, mesh = {Asbestos/*adverse effects ; Female ; Humans ; Male ; Medical History Taking ; Mesothelioma/*epidemiology/etiology ; Occupational Diseases ; Pleural Neoplasms/*epidemiology/etiology ; South Africa ; }, abstract = {Seventy consecutive patients suffering form mesothelioma of the pleura were referred to the National Research Institute for Occupational Diseases. In only 1 case was it not possible to elicit a history of significant exposure to asbestos dust. An occupational and environmental history must be taken by a knowledgeable person before it is possible to conclude that there has been no asbestos exposure.}, } @article {pmid660896, year = {1978}, author = {Li, FP and Lokich, J and Lapey, J and Neptune, WB and Wilkins, EW}, title = {Familial mesothelioma after intense asbestos exposure at home.}, journal = {JAMA}, volume = {240}, number = {5}, pages = {467}, pmid = {660896}, issn = {0098-7484}, mesh = {Adult ; Asbestos/*adverse effects ; Environmental Exposure ; Female ; Humans ; Lung Neoplasms/etiology ; Male ; Mesothelioma/etiology/*genetics ; Middle Aged ; Occupational Diseases/etiology ; Pedigree ; Pleural Neoplasms/etiology/*genetics ; }, } @article {pmid697191, year = {1978}, author = {Churg, A and Warnock, ML and Bensch, KG}, title = {Malignant mesothelioma arising after direct application of asbestos and fiber glass to the pericardium.}, journal = {The American review of respiratory disease}, volume = {118}, number = {2}, pages = {419-424}, doi = {10.1164/arrd.1978.118.2.419}, pmid = {697191}, issn = {0003-0805}, mesh = {Angina Pectoris/therapy ; Asbestos/*administration & dosage/adverse effects/therapeutic use ; *Glass ; Heart Neoplasms/*etiology/pathology ; Humans ; Male ; Mesothelioma/*etiology/pathology ; Middle Aged ; Neoplasm Metastasis ; *Pericardium/pathology ; Pleura/pathology ; *Pleural Neoplasms/pathology ; }, abstract = {A case of mesothelioma, apparently arising in the pericardium, is reported in a patient who, 15 years previously, had been treated for angina pectoris by dusting of the pericardial cavity with a mixture of fibrous dusts. At autopsy, transparent fibers and ferruginous bodies were present within the pericardium. Electron diffraction and microprobe analysis indicated that approximately two thirds of the fibers were tremolite and anthophyllite asbestos, and the remainder, fiber glass. Development of mesothelioma in laboratory animals has been reported after intrapleural deposition of asbestos and other fibers, but in humans, the link between exposure to asbestos and mesothelioma has always been based on epidemiologic data and the retrospective finding of asbestos in tissues. To our knowledge, this is the first example of a malignant mesothelioma in a human associated with direct mesothelial contact with fibrous dusts.}, } @article {pmid671123, year = {1978}, author = {Hinds, MW}, title = {Mesothelioma in the United States. Incidence in the 1970's.}, journal = {Journal of occupational medicine. : official publication of the Industrial Medical Association}, volume = {20}, number = {7}, pages = {469-471}, doi = {10.1097/00043764-197807000-00007}, pmid = {671123}, issn = {0096-1736}, mesh = {Adolescent ; Adult ; Aged ; Asbestosis/complications ; Child ; Female ; Geography ; Humans ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; United States ; }, abstract = {Mesothelioma is a rare neoplasm, the occurrence of which has been clearly related to asbestos exposure. Data recently collected by population based cancer registries in Washington, Hawaii, New Mexico, Connecticut, Michigan, Utah, Louisiana and Iowa were obtained for the determination of mesothelioma incidence rates. These registries represent a total population of over 16 million persons. Crude incidence rates were found to range from 3.0 to 7.1 per million per year. Age specific incidence rates showed a steady increase from the third through the eighth decade, with a more rapid increase for males than females. Sex specific incidence rates, age adjusted to the 1970 U.S. population, were found to range from 4.4 to 11.1 per million per year for males and from 1.2 to 3.8 per million per year for females. The highest rates for both males and females were found in the New Orleans area of Louisiana and the Puget Sound area of Washington state, both with significant shipbuilding activity.}, } @article {pmid353235, year = {1978}, author = {Levine, RJ}, title = {How the industrial physician can reduce mortality from asbestos-related diseases.}, journal = {Journal of occupational medicine. : official publication of the Industrial Medical Association}, volume = {20}, number = {7}, pages = {464-468}, doi = {10.1097/00043764-197807000-00006}, pmid = {353235}, issn = {0096-1736}, mesh = {Asbestosis/*complications ; Gastrointestinal Neoplasms/etiology/mortality/prevention & control ; Humans ; Lung Neoplasms/*etiology/mortality/prevention & control ; Neoplasms/*etiology/mortality/prevention & control ; Occupational Diseases/mortality/prevention & control ; Occupational Medicine ; Smoking ; }, abstract = {Risk indicators for asbestos-related diseases (cancers of the lung, larynx, and alimentary tract; mesothelioma; and asbestosis) and methods of early detection are reviewed and evaluated. The best medical means of reducing mortality from these diseases is to recognize particularly susceptible persons during a preemployment examination and to recommend that they not be hired for jobs involving asbestos exposure. Workers necessarily exposed to asbestos should be enrolled in a medical screening program and urged not to smoke.}, } @article {pmid668515, year = {1978}, author = {Ferlinz, R and Endres, P}, title = {[Asbestos and mesothelioma].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {103}, number = {26}, pages = {1055-1056}, doi = {10.1055/s-0028-1104813}, pmid = {668515}, issn = {0012-0472}, mesh = {Asbestos/*adverse effects ; Bronchial Neoplasms/chemically induced ; Dose-Response Relationship, Drug ; Humans ; Mesothelioma/*chemically induced ; Peritoneal Neoplasms/chemically induced ; Pleural Neoplasms/*chemically induced ; Time Factors ; }, } @article {pmid650814, year = {1978}, author = {}, title = {NIH research findings: Recent studies show workers exposed to asbestos years ago are at a greater risk for some diseases.}, journal = {JAMA}, volume = {239}, number = {23}, pages = {2431-2432}, pmid = {650814}, issn = {0098-7484}, mesh = {Air Pollutants, Occupational ; Asbestos/*adverse effects ; Female ; Humans ; Lung Neoplasms/etiology ; Male ; Mesothelioma/etiology ; Occupational Diseases/*etiology ; Risk ; Smoking/complications ; Time Factors ; United States ; }, } @article {pmid652675, year = {1978}, author = {Varkey, B and Kumar, UN}, title = {Asbestos-related diseases of lung and pleura: clinical picture and illustrative cases.}, journal = {Postgraduate medicine}, volume = {63}, number = {6}, pages = {48-66}, doi = {10.1080/00325481.1978.11714855}, pmid = {652675}, issn = {0032-5481}, mesh = {Aged ; Asbestos/*adverse effects ; Asbestosis/diagnosis ; Carcinoma, Bronchogenic/etiology ; Humans ; Lung Diseases/*etiology ; Lung Neoplasms/etiology ; Male ; Mesothelioma/etiology ; Middle Aged ; Occupational Diseases/etiology ; Pleural Diseases/*etiology ; Pleural Effusion/etiology ; Pleural Neoplasms/etiology ; }, abstract = {Exposure to asbestos may occur in any of a large number of occupations, and the latent period from exposure to appearance of clinical or roentgenologic evidence of related disease of the lung or pleura, or both, may be more than 20 years. A complete occupational history is therefore of paramount importance in the detection of asbestos-related diseases. Illustrative cases highlight the features of benign and malignant diseases of the lung and pleura for which a causal relationship to asbestos exposure is probable or established.}, } @article {pmid77365, year = {1978}, author = {Vianna, NJ and Polan, AK}, title = {Non-occupational exposure to asbestos and malignant mesothelioma in females.}, journal = {Lancet (London, England)}, volume = {1}, number = {8073}, pages = {1061-1063}, doi = {10.1016/s0140-6736(78)90911-x}, pmid = {77365}, issn = {0140-6736}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Environmental Exposure ; Female ; Humans ; Interpersonal Relations ; Male ; Mesothelioma/*etiology/genetics ; Middle Aged ; New York ; Occupations ; Peritoneal Neoplasms/*etiology/genetics ; Pleural Neoplasms/*etiology/genetics ; Risk ; }, abstract = {A study of the occupational histories of 52 females with malignant mesothelioma and certain of their relatives, carried out to measure the risk of this disorder attributable to indirect asbestos exposure, showed that a significantly greater number of husbands and fathers of cases than of controls worked in asbestos-related industries, and the relative risk for this factor was 10. The frequency of parental cancer, especially gastrointestinal malignancy, was also significantly greater for cases than for their controls. This raises the possibility of a genetic predisposition to malignant mesothelioma.}, } @article {pmid658962, year = {1978}, author = {Chen, WJ and Mottet, NK}, title = {Malignant mesothelioma with minimal asbestos exposure.}, journal = {Human pathology}, volume = {9}, number = {3}, pages = {253-258}, doi = {10.1016/s0046-8177(78)80083-5}, pmid = {658962}, issn = {0046-8177}, mesh = {Asbestos/isolation & purification ; Asbestosis/*pathology ; Humans ; Lung/pathology ; Lung Neoplasms/*pathology ; Male ; Mesothelioma/*pathology ; Middle Aged ; }, abstract = {The association of malignant mesothelioma and asbestos fibers is well established. The minimal exposure that may produce the tumor is not known. The present report documents the minimal exposure by thorough examination of occupational history and personal hobbies, and counting of the number of asbestos fibers in the lungs. The evidence for the elemental composition of asbestos fibers by electron probe (EDAX) is also presented.}, } @article {pmid656299, year = {1978}, author = {Davis, JM and Beckett, ST and Bolton, RE and Collings, P and Middleton, AP}, title = {Mass and number of fibres in the pathogenesis of asbestos-related lung disease in rats.}, journal = {British journal of cancer}, volume = {37}, number = {5}, pages = {673-688}, pmid = {656299}, issn = {0007-0920}, mesh = {Animals ; *Asbestos ; Lung/pathology ; Lung Neoplasms/etiology/*pathology ; Mesothelioma/etiology ; Neoplasms, Experimental/etiology/pathology ; Pulmonary Fibrosis/etiology/*pathology ; Rats ; }, abstract = {Five groups of rats were treated by inhalation for 12 months, with the U.I.C.C. preparations of the 3 main commercially used asbestos types, chrysotile, crocidolite and amosite. The experiment was designed so that the effects of both fibre mass and fibre number could be examined. The results indicated that chrysotile dust caused far more lung fibrosis than either amphibole type even when the fibre numbers in the dust clouds were similar. All malignant pulmonary neoplasms found during this study occurred in animals treated with chrysotile. The fibre-number calculations used for the generation of dust clouds were evaluated using the parameters recommended by the Health and Safety Executive in 1976, by which all fibres over 5 microgram long are counted using a phase-contrast light microscopy. When fibre-length distributions were calculated using a scanning electron microscope, however, it was found that the chrysotile clouds used in this study contained many more fibres over 20 microgram long than either of the amphibole clouds. The results, therefore, support previous suggestions that long asbestos fibres are more dangerous than short. They also indicate that neither a single mass standard, nor the present fibre-number standards are satisfactory.}, } @article {pmid668660, year = {1978}, author = {Thomson, R and Kilroe-Smith, TA and Webster, I}, title = {The effect of asbestos-associated metal ions on the binding of benzo(a)pyrene to macromolecules in vitro.}, journal = {Environmental research}, volume = {15}, number = {2}, pages = {309-319}, doi = {10.1016/0013-9351(78)90106-8}, pmid = {668660}, issn = {0013-9351}, mesh = {Animals ; *Asbestos ; Benzopyrenes/*metabolism ; DNA/*metabolism ; Humans ; In Vitro Techniques ; Male ; Mesothelioma/etiology ; Metals/metabolism/*pharmacology ; Microsomes, Liver/metabolism ; Mining ; Neoplasms/etiology ; Protein Biosynthesis ; Rats ; Smoking ; Trace Elements/metabolism ; }, } @article {pmid663877, year = {1978}, author = {Baris, YI and Sahin, AA and Ozesmi, M and Kerse, I and Ozen, E and Kolacan, B and Altinörs, M and Göktepeli, A}, title = {An outbreak of pleural mesothelioma and chronic fibrosing pleurisy in the village of Karain/Urgüp in Anatolia.}, journal = {Thorax}, volume = {33}, number = {2}, pages = {181-192}, pmid = {663877}, issn = {0040-6376}, mesh = {Adult ; Age Factors ; Aged ; Asbestos/analysis ; Chronic Disease ; Disease Outbreaks/*epidemiology ; Environment ; Female ; Humans ; Male ; Mesothelioma/*epidemiology/ultrastructure ; Microscopy, Electron ; Middle Aged ; Pleural Neoplasms/*epidemiology/ultrastructure ; Pleurisy/*epidemiology/pathology ; Soil/analysis ; Turkey ; Water Supply/analysis ; }, abstract = {The 575 inhabitants of the remote Anatolian village of Karain suffered 11 deaths from pleural mesothelioma in 1975/76 and there were five cases of fibrosing pleurisy. In the previous five years there had been 25 cases of mesothelioma. Calcified pleural plaques were common on survey radiography. Asbestos does not occur in the local soil or rock, nor is it handled in the village, but a few fibres were found in the water. Fibres were also found in the pleural tissue of two of five cases examined. Inhabitants of the neighbouring villages are free of mesothelioma.}, } @article {pmid634196, year = {1978}, author = {Weicksel, P}, title = {[Asbestos fibre dust, an actual hazard (author's transl)].}, journal = {Medizinische Klinik}, volume = {73}, number = {10}, pages = {351-356}, pmid = {634196}, issn = {0025-8458}, mesh = {Air Pollution ; Asbestos/*adverse effects ; Asbestosis/*complications/diagnostic imaging ; *Dust ; Electrocardiography ; Environmental Exposure ; Germany, West ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/etiology ; Occupational Diseases ; Radiography ; Radionuclide Imaging ; }, abstract = {Late results concerning the effects of fibre dust in the human lungs have enormously raised the actuality of fibronous and cancerous reactions of airborne asbestos fibres. The hithero experiences with diseases, resultant from airborne asbestos fibres (asbestoses, cancer, and mesothelioma) are looked on and discussed with respect to 2 asbestos diseases out of the office of the author. Special attention is given to the asbestos-caused mesothelioma which has also been affiliated in the 7th decree of diseases resulting from the work (Berufskrankheitenverordnung) on the 1.1. 1977. Own experiences resulting as well from preventive control examinations as from special collectives of patients (workers in asbestos contaminated surroudnings and smokers) are discussed with respect to restrictive or obstructive ventilation problems. Finally some examples of asbestos free materials wich could be used substiutionarily are quoted.}, } @article {pmid76030, year = {1978}, author = {Peto, J}, title = {The hygiene standard for chrysotile asbestos.}, journal = {Lancet (London, England)}, volume = {1}, number = {8062}, pages = {484-489}, doi = {10.1016/s0140-6736(78)90145-9}, pmid = {76030}, issn = {0140-6736}, mesh = {Asbestos/*toxicity ; Asbestosis/epidemiology/*mortality ; England ; Humans ; Male ; Maximum Allowable Concentration ; Mesothelioma/etiology/mortality ; *Mining ; Models, Biological ; Occupational Medicine/*standards ; Respiratory Tract Neoplasms/epidemiology/etiology/mortality ; }, abstract = {Previous studies, including the analysis on which the current 2 fibres/cm3 hygiene standard is based, may have underestimated the risk of morbidity or mortality following exposure to low levels of asbestos dust. Accurate dose-response data at levels below 2 fibres/cm3 are unlikely to be available for the foreseeable future, and the biologically plausible assumption that excess cancer mortality is approximately proportional to dust level should be provisionally accepted. It may be reasonable, however, to postulate a safe threshold for mortality from asbestosis. If excess mortality from asbestos-related disease is proportional to dust level for each cause, approximately 10% of male asbestos workers might, under certain assumptions, eventually die of asbestos-induced disease after 50 years' exposure at 2 fibres/cm3. Peritoneal mesothelioma is usually due to crocidolite (blue asbestos) or other amphiboles, but exposure to chrysotile (white asbestos) alone may lead to a substantial risk of pleural mesothelioma. These predictions are based on rather small numbers in a single factory, and further studies in other working environments are required. Fibre counts based on optical microscopy are likely to be less relevant than total counts by electron microscopy, and excess mortality is virtually confined to men first exposed more than 20 years ago, when little or no accurate data on dust levels were collected.}, } @article {pmid417776, year = {1978}, author = {Selikoff, IJ and Hammond, EC}, title = {Asbestos-associated disease in United States shipyards.}, journal = {CA: a cancer journal for clinicians}, volume = {28}, number = {2}, pages = {87-99}, doi = {10.3322/canjclin.28.2.87}, pmid = {417776}, issn = {0007-9235}, mesh = {Asbestos/*toxicity ; Asbestosis/etiology ; Environmental Exposure ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Occupational Diseases/*etiology ; *Ships ; }, } @article {pmid276234, year = {1978}, author = {Whitaker, D and Shilkin, KB}, title = {The cytology of malignant mesothelioma in Western Australia.}, journal = {Acta cytologica}, volume = {22}, number = {2}, pages = {67-70}, pmid = {276234}, issn = {0001-5547}, mesh = {Asbestos/adverse effects ; Australia ; Cytodiagnosis ; Diagnosis, Differential ; Humans ; Mesothelioma/chemically induced/*diagnosis ; Pleural Effusion/*cytology ; Pleural Neoplasms/chemically induced/*diagnosis ; }, abstract = {The cytology of malignant mesothelioma seen in 12 patients associated with the mining of crocidolite asbestos in Western Australia is described. Two main patterns of mesothelioma were observed: the spindle cell and epithelial varieties. In the more common epithelial variety, five features were found to be of particular value in making a cytologic diagnosis. These include the finding of cell aggregates, multinucleation, the presence of brush-like borders, the close apposition of cell borders, and a characteristic cytoplasm. A diagnosis of malignant mesothelioma may be established by cytologic examination of effusions. The awareness of the possible occurrence of such a primary malignant neoplasm with the features outlined may be helpful in this regard.}, } @article {pmid648028, year = {1978}, author = {Haslam, PL and Lukoszek, A and Merchant, JA and Turner-Warwick, M}, title = {Lymphocyte responses to phytohaemagglutinin in patients with asbestosis and pleural mesothelioma.}, journal = {Clinical and experimental immunology}, volume = {31}, number = {2}, pages = {178-188}, pmid = {648028}, issn = {0009-9104}, mesh = {Adult ; Aged ; Asbestosis/*immunology ; Female ; Humans ; Hypersensitivity, Delayed ; Lectins ; Lung Neoplasms/immunology ; Lymphocyte Activation ; Lymphocytes/*immunology ; Male ; Mesothelioma/*immunology ; Middle Aged ; Pleural Neoplasms/*immunology ; }, abstract = {Quantitative impairment of lymphocyte responses to phytohaemagglutinin (PHA) has been demonstrated in six (21%) out of twenty-eight patients with asbestos-associated pulmonary fibrosis, in comparison with a group of unexposed normal controls. The impairment tended to occur in patients with fairly severe fibrosis, comparatively short duration of exposure to asbestos dust and with increases in serum immunoglobulin levels. One patient with asbestosis and an associated bronchial carcinoma also had depressed lymphocyte responses to PHA. These findings suggest a relationship between defective T-lymphocyte function and the fibrotic response in asbestosis. Whether it is also linked with the development of lung cancer, occurring either before or at a pre-clinical stage of tumour growth, and is of value in identifying patients especially at risk should now be explored in longitudinal studies. However, eight out of ten patients with asbestos-associated pleural mesothelioma and without lung fibrosis showed no evidence of impaired cellular immunity, either by in vitro testing with PHA or by vivo delayed hypersensitivity skin testing, indicating that impaired T-lymphocyte function is unlikely to be a common finding in all types of asbestos-associated malignancy.}, } @article {pmid644536, year = {1978}, author = {Edge, JR and Choudhury, SL}, title = {Malignant mesothelioma of the pleura in Barrow-in-Furness.}, journal = {Thorax}, volume = {33}, number = {1}, pages = {26-30}, pmid = {644536}, issn = {0040-6376}, mesh = {Adult ; Aged ; Asbestos/analysis ; Asbestosis/complications ; Female ; Humans ; Lung/analysis/pathology ; Male ; Mesothelioma/*diagnosis/etiology/pathology ; Middle Aged ; Neoplasm Metastasis ; Occupational Diseases/etiology ; Pleural Neoplasms/*diagnosis/etiology/pathology ; Ships ; }, abstract = {Ffty cases of malignant pleural mesothelioma (47 men and 3 women) have been diagnosed during the period 1966-76 in Barrow-in-Furness, all of them histologically proved and accepted by the Pneumoconiosis Panel. At the time of writing only three survive. There was a history of industrial exposure to asbestos in all 47 men, who had worked in various trades in the shipyard, as had one of the women. One of the women was married to a shipyard plumber, who may have brought home asbestos dust on his clothes. Only one patient, a housewife, aged 28 at diagnosis, had no known asbestos contact. The asbestos content of the lungs has been measured in the last 20 cases, in 18 of whom it was found to be substantially greater than the accepted levels for the general population. In a small number studied by electron microscopy, the predominant fibre was crocidolite. A positive histological diagnosis was achieved in 39 subjects during life in the expectation of securing industrial compensation, but, in spite of this, less than half of the dependants are currently receiving payments. Metastases, though never clinically apparent, were frequent at necropsy.}, } @article {pmid745588, year = {1978}, author = {Perry, MC and Solinger, A and Farhangi, M and Luger, A}, title = {Plasmacytomas and mesothelioma.}, journal = {Medical and pediatric oncology}, volume = {5}, number = {1}, pages = {205-212}, doi = {10.1002/mpo.2950050128}, pmid = {745588}, issn = {0098-1532}, mesh = {Asbestos ; Carcinogens, Environmental ; Humans ; Male ; Mesothelioma/*complications/pathology ; Middle Aged ; Neoplasms, Multiple Primary/*etiology ; Occupational Diseases/etiology ; Plasmacytoma/*complications/pathology ; Pleural Neoplasms/*complications/pathology ; }, abstract = {A patient is reported who developed five plasmacytomas over a four-year period and developed a pleural mesothelioma 12 years later. The relationship of these two entities is discussed and the question of a common environmental carcinogen is raised.}, } @article {pmid629592, year = {1978}, author = {Thériault, GP and Grand-Bois, L}, title = {Mesothelioma and asbestos in the Province of Quebec, 1969-1972.}, journal = {Archives of environmental health}, volume = {33}, number = {1}, pages = {15-19}, doi = {10.1080/00039896.1978.10667302}, pmid = {629592}, issn = {0003-9896}, mesh = {Asbestos/*toxicity ; Female ; Humans ; Male ; Mesothelioma/*epidemiology ; Occupations ; Peritoneal Neoplasms/epidemiology ; Pleural Neoplasms/epidemiology ; Quebec ; Sex Factors ; Smoking/epidemiology ; }, abstract = {All records of patients who died of mesothelioma in the Province of Quebec during the period 1969-1972 were collected and reviewed. Asbestos exposure in this group was compared with that in two control groups, one of persons dying of accidental causes and the other of those dying of cardiovascular disease. The mortality rate for mesothelioma was estimated at between 2.3 and 2.8 per million per year. Men were affected twice as frequently as women, this difference being related exclusively to pleural mesothelioma. The incidence in urban regions was much higher than in rural areas, and areas involved in mining showed an incidence in the expected range. Thirty-four percent of the patients with mesothelioma and only 2% of controls had histories of direct exposure to asbestos. This exposure was related to asbestos processing and not its production. No woman gave a history of occupational exposure to asbestos. It appeared that chrysotile may be less related to the production of mesothelioma than other types of asbestos fibers.}, } @article {pmid152898, year = {1978}, author = {Kannerstein, M and Churg, J and McCaughey, WT}, title = {Asbestos and mesothelioma: a review.}, journal = {Pathology annual}, volume = {13 Pt 1}, number = {}, pages = {81-129}, pmid = {152898}, issn = {0079-0184}, mesh = {Animals ; Asbestos/*adverse effects ; Asbestosis ; Diagnosis, Differential ; Environmental Exposure ; Glycosaminoglycans/analysis ; Humans ; Hyaluronic Acid/analysis ; Lung/pathology ; Lung Neoplasms/*etiology/pathology ; Mesothelioma/epidemiology/*etiology/pathology ; Occupational Diseases/etiology ; Peritoneal Neoplasms/*etiology/pathology ; Phagocytosis ; Pleural Effusion/analysis ; }, } @article {pmid77474, year = {1978}, author = {Chahinian, AP and Holland, JF}, title = {Treatment of diffuse malignant mesothelioma: a review.}, journal = {The Mount Sinai journal of medicine, New York}, volume = {45}, number = {1}, pages = {54-67}, pmid = {77474}, issn = {0027-2507}, mesh = {Asbestos/adverse effects ; Humans ; Mesothelioma/etiology/radiotherapy/surgery/*therapy ; Palliative Care ; Peritoneal Neoplasms/etiology/radiotherapy/surgery/*therapy ; Pleural Neoplasms/etiology/radiotherapy/surgery/*therapy ; Prognosis ; }, } @article {pmid73906, year = {1977}, author = {}, title = {Asbestos.}, journal = {Lancet (London, England)}, volume = {2}, number = {8050}, pages = {1211-1212}, pmid = {73906}, issn = {0140-6736}, mesh = {Asbestos/*adverse effects ; Canada ; Environmental Exposure ; Female ; Humans ; Lung Neoplasms/*chemically induced ; Male ; Mesothelioma/*chemically induced ; Occupational Diseases/*chemically induced ; United Kingdom ; United States ; }, } @article {pmid337935, year = {1977}, author = {Kannerstein, M and Churg, J and McCaughey, E and Selikoff, IJ}, title = {Pathogenic effects of asbestos.}, journal = {Archives of pathology & laboratory medicine}, volume = {101}, number = {12}, pages = {623-628}, pmid = {337935}, issn = {0003-9985}, mesh = {Adenocarcinoma/etiology ; Animals ; Asbestos/*adverse effects/pharmacology ; Asbestosis/epidemiology/etiology/pathology ; Cells/drug effects ; Humans ; In Vitro Techniques ; Lung Neoplasms/etiology ; Macrophages/physiology ; Mesothelioma/etiology ; Phagocytosis ; Pleura/pathology ; Pleural Diseases/etiology/pathology ; Respiratory Tract Diseases/*etiology ; United States ; }, abstract = {The enormous increase in the use of asbestos during this century has necessitated the intensive study of its pathogenic effects. The occurrence of pulmonary parenchymal and pleural fibrosis and an increased prevalence of pulmonary and gastrointestinal carcinoma and of pleural and peritoneal mesothelioma have been established. A relationship, also, to laryngeal carcinoma is probable. Mesothelioma has been associated with indirect occupational, domestic, and neighborhood exposure, and the possibility of a similar correlation of pulmonary carcinoma with low exposure has been suggested. Pulmonary fibrosis and pleural plaques have been demonstrated under these circumstances. The physical characteristics of the asbestos fiber appear to be the principal factors in its carcinogenic action. The ability of fine, short fibers, especially fragmented chrysotile, to reach the pleura would appear to account for many of the pathogenetic and anatomical features of asbestos-related disease.}, } @article {pmid927303, year = {1977}, author = {Weicksel, P}, title = {[Pleural and peritoneal mesothelioma].}, journal = {Medizinische Klinik}, volume = {72}, number = {47}, pages = {2005-2011}, pmid = {927303}, issn = {0025-8458}, mesh = {Asbestos/adverse effects ; England ; Germany, West ; Humans ; Mesothelioma/chemically induced/*epidemiology ; Netherlands ; Occupational Diseases/chemically induced ; Peritoneal Neoplasms/chemically induced/*epidemiology ; Pleural Neoplasms/chemically induced/*epidemiology ; }, } @article {pmid591074, year = {1977}, author = {Arul, KJ and Holt, PF}, title = {Mesothelioma possibly due to environmental exposure to asbestos in childhood.}, journal = {International archives of occupational and environmental health}, volume = {40}, number = {2}, pages = {141-143}, pmid = {591074}, issn = {0340-0131}, mesh = {Adult ; Air Pollutants/adverse effects ; Asbestos/*adverse effects ; Environmental Exposure ; Female ; Humans ; Mesothelioma/*chemically induced ; Pleural Neoplasms/*chemically induced ; Time Factors ; }, } @article {pmid921093, year = {1977}, author = {Legha, SS and Muggia, FM}, title = {Pleural mesothelioma: clinical features and therapeutic implications.}, journal = {Annals of internal medicine}, volume = {87}, number = {5}, pages = {613-621}, doi = {10.7326/0003-4819-87-5-613}, pmid = {921093}, issn = {0003-4819}, mesh = {Asbestos/toxicity ; Humans ; *Mesothelioma/diagnosis/etiology/therapy ; Pleural Effusion/analysis ; *Pleural Neoplasms/diagnosis/etiology/therapy ; }, abstract = {A detailed review of the literature was done to define the epidemiology, pathology, clinical features, and treatment of pleural mesothelioma. It appears that pleural mesothelioma accounts for approximately 400 deaths each year in the United States. Asbestos has been definitely implicated in the etiology of this disease. The common clinical features include chest pain, pleural effusion, and radiologic findings of irregular pleural thickening or pleural densities. Therapeutic modalities used in the past have included surgery, radiation therapy, and, more recently, chemotherapy. A combined modality approach to treatment appears more promising.}, } @article {pmid72256, year = {1977}, author = {Davies, D}, title = {Community exposure to asbestos.}, journal = {Lancet (London, England)}, volume = {2}, number = {8044}, pages = {924}, doi = {10.1016/s0140-6736(77)90851-0}, pmid = {72256}, issn = {0140-6736}, mesh = {*Asbestosis/complications ; England ; Environmental Exposure ; Germany, West ; Humans ; Mesothelioma/etiology ; *Pleural Diseases/complications ; }, } @article {pmid588440, year = {1977}, author = {Morgan, A and Davies, P and Wagner, JC and Berry, G and Holmes, A}, title = {The biological effects of magnesium-leached chrysotile asbestos.}, journal = {British journal of experimental pathology}, volume = {58}, number = {5}, pages = {465-473}, pmid = {588440}, issn = {0007-1021}, mesh = {Adsorption ; Animals ; *Asbestos/toxicity ; Female ; Glycoside Hydrolases/metabolism ; Hemolysis ; L-Lactate Dehydrogenase/metabolism ; Macrophages/drug effects/enzymology ; *Magnesium ; Male ; Mesothelioma/chemically induced ; Mice ; Serum Albumin ; }, abstract = {Chrysotile asbestos was leached in N hydrochloric acid for varying times to produce a range of magnesium-depleted samples. The protein adsorptive capacity, the haemolytic activity, and the capacity to cause selective release of acid hydrolases from macrophages were measured for the various samples in vitro. The carcinogenicity of the same materials was determined following intrapleural inoculation in rats. The adsorptive capacity for albumin decreased linearly with magnesium removal. The haemolytic activity also declined until about half the magnesium had been removed, after which there was little further change. The selective release of acid hydrolases from macrophages in culture increased up to the point at which half the magnesium had been removed but by 90% depletion had declined rapidly. The carcinogenicity of 50% -depleted chrysotile was similar to that of intact, but at 90% depletion the incidence of mesothelial tumours had fallen considerably. There was no evidence that the leached samples fragmented more than the unleached in vivo.}, } @article {pmid914521, year = {1977}, author = {Forck, G}, title = {[Amendment to the 7th Decree on Occupational diseases].}, journal = {Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete}, volume = {28}, number = {9}, pages = {492-494}, pmid = {914521}, issn = {0017-8470}, mesh = {Asbestos/adverse effects ; Byssinosis ; Farmer's Lung ; Germany, West ; Humans ; *Legislation, Medical ; Mesothelioma/chemically induced ; *Occupational Diseases ; Peritoneal Neoplasms/chemically induced ; Pleural Neoplasms/chemically induced ; Vascular Diseases/etiology ; Vibration/adverse effects ; }, } @article {pmid333420, year = {1977}, author = {McDonald, JC and McDonald, AD}, title = {Epidemiology of mesothelioma from estimated incidence.}, journal = {Preventive medicine}, volume = {6}, number = {3}, pages = {426-442}, doi = {10.1016/0091-7435(77)90025-1}, pmid = {333420}, issn = {0091-7435}, mesh = {Adolescent ; Adult ; Asbestos/adverse effects ; Canada ; Europe ; Female ; Heart Neoplasms/epidemiology/etiology ; Humans ; Lung Neoplasms/mortality ; Male ; Mesothelioma/*epidemiology/etiology/mortality ; Middle Aged ; Occupational Diseases/epidemiology/etiology/mortality ; Pericardium ; Peritoneal Neoplasms/epidemiology/etiology ; Pleural Neoplasms/epidemiology/etiology/mortality ; United States ; }, } @article {pmid929482, year = {1977}, author = {Whitwell, F and Scott, J and Grimshaw, M}, title = {Relationship between occupations and asbestos-fibre content of the lungs in patients with pleural mesothelioma, lung cancer, and other diseases.}, journal = {Thorax}, volume = {32}, number = {4}, pages = {377-386}, pmid = {929482}, issn = {0040-6376}, mesh = {Adult ; Aged ; Asbestos/*adverse effects/analysis ; Asbestosis/pathology ; Environmental Exposure ; Female ; Humans ; Lung/pathology ; Lung Neoplasms/*chemically induced ; Male ; Mesothelioma/*chemically induced ; Middle Aged ; Occupational Diseases/*chemically induced ; Pleural Neoplasms/*chemically induced ; }, abstract = {Whitwell, F., Scott, Jean, and Grimshaw, Myra (1977).Thorax, 32, 377-386. Relationship between occupations and asbestos-fibre content of the lungs in patients with pleural mesothelioma, lung cancer, and other diseases. The light-visible asbestos-fibre content of 300 lung specimens has been measured using a potash-digestion and phase-contrast microscopy technique, and the results have been correlated with the occupations of the patients. Among 100 pleural mesothelioma specimens were 88 where the patients had been exposed to asbestos, and in 73 of these (83%) the lung tissue contained over 100 000 asbestos fibres per gram of dried lung, and only one specimen showed less than 20 000 fibres per gram. When asbestosis was present, the lungs nearly always showed over 3 million fibres per gram. In 100 control lungs (those without industrial disease or lung cancer) there were less than 20 000 fibres per gram of dried lung in 71% of specimens. Lungs from 100 patients with lung cancer but no industrial disease contained less than 20 000 fibres per gram of dried lung in 80% of cases. Patients with parietal pleural plaques nearly all had over 20 000 fibres per gram in their lungs. The number of asbestos fibres found in the lungs was closely related to the occupations of the patients but not to their home environment. Patients who had lived near likely sources of atmospheric asbestos pollution did not have higher asbestos fibre counts than the rest of the patients. It is concluded that there is a definite dose relationship between asbestos exposure and mesothelioma formation but that' `sub-asbestosis' levels of asbestos exposure do not contribute to the formation of lung cancer in those not subjected to industrial asbestos exposure.}, } @article {pmid911687, year = {1977}, author = {Elmes, PC and Simpson, MJ}, title = {Insulation workers in Belfast. A further study of mortality due to asbestos exposure (1940-75).}, journal = {British journal of industrial medicine}, volume = {34}, number = {3}, pages = {174-180}, pmid = {911687}, issn = {0007-1072}, mesh = {Adult ; Aged ; Asbestosis/*mortality ; Bronchial Neoplasms/mortality ; Follow-Up Studies ; Humans ; Male ; Mesothelioma/mortality ; Middle Aged ; Northern Ireland ; Respiratory Tract Diseases/mortality ; Ships ; }, abstract = {A follow-up study of 162 men already working as insulators (laggers) in 1940 has been extended from 1965 to 1975. By the end of 1975 there were 40 survivors when 108 had been expected. Until 1965 there had been an overall excess of deaths; these were due to asbestosis with or without tuberculosis and to alimentary cancer, as well as to bronchial carcinoma and mesothelioma. From 1965 onwards the overall death rate among survivors is not so excessive but there is still a marked excess of deaths from bronchial cancer and mesothelioma. The continued risk of death attributable to malignancy after asbestosis had ceased to contribute directly, does not appear to be caused by any changes which occurred before 1940 in the conditions at work.}, } @article {pmid911686, year = {1977}, author = {Peto, J and Doll, R and Howard, SV and Kinlen, LJ and Lewinsohn, HC}, title = {A mortality study among workers in an English asbestos factory.}, journal = {British journal of industrial medicine}, volume = {34}, number = {3}, pages = {169-173}, pmid = {911686}, issn = {0007-1072}, mesh = {Adult ; Asbestos/*adverse effects ; England ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/chemically induced/mortality ; Male ; Mesothelioma/chemically induced/mortality ; Occupational Diseases/*mortality ; Pleural Neoplasms/chemically induced/mortality ; Respiratory Tract Diseases/mortality ; *Textile Industry ; }, abstract = {The previous report on this cohort study of workers in an asbestos textile factory (Knox et al., 1968) showed little evidence of increased mortality among workers who had entered the factory after the implementation in 1932 of the first Asbestos Industry Regulation (1931) but observed that no firm conclusions could be drawn, as little carcinogenic effect would be expected for 20 years after first exposure. A further 8 1/2 years of follow-up has revealed some asbestos-related disease in this latter group, although very much less than for employees first exposed before 1933. Among the 963 workers first exposed in 1933 or later, mortality was increased for carcinoma of the bronchus (31 deaths; 19-3 expected for all lung cancers) and non-malignant respiratory disease (35 deaths, 25-0 expected), and a further 5 deaths were attributed to pleural mesothelioma.}, } @article {pmid336069, year = {1977}, author = {Constantinidis, K}, title = {Asbestos exposure--its related disorders.}, journal = {The British journal of clinical practice}, volume = {31}, number = {7-8}, pages = {89-101}, pmid = {336069}, issn = {0007-0947}, mesh = {Animals ; Asbestos/*adverse effects ; Asbestosis/diagnostic imaging/physiopathology ; Environmental Exposure ; Humans ; Lung Neoplasms/chemically induced ; Mesothelioma/chemically induced ; Occupational Diseases/*chemically induced ; Peritoneal Neoplasms/chemically induced ; Pleural Diseases/chemically induced ; Pleural Neoplasms/chemically induced ; Radiography ; }, } @article {pmid855957, year = {1977}, author = {Hasan, FM and Nash, G and Kazemi, H}, title = {The significance of asbestos exposure in the diagnosis of mesothelioma: a 28-year experience from a major urban hospital.}, journal = {The American review of respiratory disease}, volume = {115}, number = {5}, pages = {761-768}, doi = {10.1164/arrd.1977.115.5.761}, pmid = {855957}, issn = {0003-0805}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Asbestosis/complications ; Environmental Exposure ; Female ; Humans ; Lung Neoplasms/chemically induced/*diagnosis ; Male ; Mesothelioma/chemically induced/*diagnosis ; Middle Aged ; Occupational Medicine ; Retrospective Studies ; Ships ; }, abstract = {A continued increase in the incidence of diffuse mesothelioma has been attributed to greater industrial use of asbestos but is also due in part to wider acceptance of this tumor by pathologists. In this retrospective study, the epidemiology, clinical presentation, and pathology of asbestos and non-asbestos-related mesothelioma from a major urban hospital were reviewed. Of the 36 cases of mesothelioma on file, 19 were not associated with exposure to asbestos. Although a retrospective study raises the possibility of inadequate occupational histories, the lack of history of asbestos exposure correlated with postmortem histology by light microscopy. When postmortem material was reviewed, evidence of asbestos exposure was present in all cases of mesothelioma with history of exposure to asbestos, and in no cases in which the patient denied history of asbestos exposure. Using strict histologic and histochemical criteria, the diagnosis of mesothelioma was confirmed in 8 of 9 patients with asbestos-related mesothelioma but in only 4 of 13 cases of non-asbestos-related mesothelioma. The diagnosis of diffuse methelioma is often difficult to make even wtih complete autopsy examinations. It should be entertained only with adherence to strict clinical and pathologic criteria, especially in women with no history to exposure to asbestos dust.}, } @article {pmid868753, year = {1977}, author = {Moll, KD and Tihansky, DP}, title = {Risk-benefit analysis for industrial and social needs.}, journal = {American Industrial Hygiene Association journal}, volume = {38}, number = {4}, pages = {153-161}, doi = {10.1080/0002889778507931}, pmid = {868753}, issn = {0002-8894}, mesh = {Air Pollutants/analysis ; Asbestos ; Asbestosis/complications ; Costs and Cost Analysis ; *Environmental Exposure ; Environmental Pollution/prevention & control ; Government Agencies ; Humans ; *Industry ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; Models, Theoretical ; Monitoring, Physiologic ; Respiratory Tract Diseases/etiology ; Risk ; }, abstract = {This study develops a decision method for evaluating the social acceptability of industrial controls on hazardous materials. Decisions are based on a "multiple criteria approach" that jointly considers measures such as risk-benefit tradeoff, minimum reducible health risk, maximum acceptable cost and implicit value of human life. Health risks are calculated by combining separate estimates of production and usage patterns, emissions to air and water, effectiveness of controls, pollutant dispersion and human susceptibility. Economic benefits consider employment, trade and consumer impacts, as well as direct costs of controls. The analysis focuses on asbestos as an example hazard. Relative values of hazard reduction alternatives are examined for asbestos manufacturing exhaust filters and for asbestos substitutes in brake linings. Preliminary calculations indicate risk reductions of these alternatives cannot justify their social costs.}, } @article {pmid866290, year = {1977}, author = {Woitowitz, HJ and Valentin, H}, title = {[Asbestosis and asbestos related tumours; assessment of disablement (author's transl)].}, journal = {Praxis der Pneumologie}, volume = {31}, number = {3}, pages = {153-159}, pmid = {866290}, issn = {0032-7069}, mesh = {Asbestos/*adverse effects ; Asbestosis/*diagnosis ; Humans ; Mesothelioma/*chemically induced ; Peritoneal Neoplasms/*chemically induced ; Pleural Neoplasms/*chemically induced ; Prognosis ; }, } @article {pmid845325, year = {1977}, author = {Bruckman, L and Rubino, RA and Christine, B}, title = {Asbestos and mesothelioma incidence in Connecticut.}, journal = {Journal of the Air Pollution Control Association}, volume = {27}, number = {2}, pages = {121-126}, doi = {10.1080/00022470.1977.10470400}, pmid = {845325}, issn = {0002-2470}, mesh = {Age Factors ; Air/analysis ; *Asbestos/analysis ; Connecticut ; Female ; Humans ; Male ; Mesothelioma/*epidemiology ; Occupations ; }, } @article {pmid835626, year = {1977}, author = {Kannerstein, M and Churg, J and McCaughey, WT and Hill, DP}, title = {Papillary tumors of the peritoneum in women: mesothelioma or papillary carcinoma.}, journal = {American journal of obstetrics and gynecology}, volume = {127}, number = {3}, pages = {306-314}, doi = {10.1016/0002-9378(77)90475-6}, pmid = {835626}, issn = {0002-9378}, mesh = {Adult ; Aged ; Carcinoma, Papillary/*pathology ; Child, Preschool ; Female ; Humans ; Male ; Mesothelioma/*pathology ; Middle Aged ; Neoplasm Metastasis ; Ovarian Neoplasms/pathology ; Peritoneal Neoplasms/*pathology ; }, abstract = {It has been urged recently that the surface tumors of the ovary be classified as mesotheliomas because both of these neoplasms have a common ancestry. It was suggested also that the rare extragonadal peritoneal tumor of a microscopic morphology similar to that of the ovarian tumor be considered as a mesothelioma. In the present report, objections to this classification are offered. Fifteen cases of diffuse and/or localized peritoneal tumors interpreted as papillary carcinoma arising from extraovarian tissue of Müllerian potentiality are described, and distinctions from mesothelioma are pointed out. Reasons for opposing the grouping of ovarian carcinoma or extragonadal papillary carcinoma of the peritoneum with mesothelioma include the need for categorizing the latter separately in order to monitor its association with asbestos exposure and the possibility that biological differences between these tumors may lead to the development of different modes of therapy.}, } @article {pmid929770, year = {1977}, author = {Elmes, PC}, title = {Investigation into the hazardous use of asbestos. Northern Ireland 1960-76.}, journal = {The Ulster medical journal}, volume = {46}, number = {2}, pages = {71-80}, pmid = {929770}, issn = {0041-6193}, mesh = {Aged ; Asbestos/*adverse effects ; Humans ; Mesothelioma/*chemically induced ; Middle Aged ; Northern Ireland ; Pleural Neoplasms/*chemically induced ; }, } @article {pmid909393, year = {1977}, author = {Barcat, JA and Croxatto, JO}, title = {[Malignant pleural mesotheliomas. Anatomical study and clinical description of 5 cases].}, journal = {Medicina}, volume = {37 Suppl 2}, number = {}, pages = {59-69}, pmid = {909393}, issn = {0025-7680}, mesh = {Aged ; Asbestos/adverse effects ; Biopsy ; Female ; Humans ; Male ; Mesothelioma/etiology/*pathology ; Middle Aged ; Pleural Neoplasms/etiology/*pathology ; }, } @article {pmid882486, year = {1977}, author = {Moigneteau, C and Touzeau, PY and Guillement, JM}, title = {[Asbestosic pleural calcifications and the associated pathology (study of 32 cases)].}, journal = {Le Poumon et le coeur}, volume = {33}, number = {2}, pages = {101-106}, pmid = {882486}, issn = {0032-5821}, mesh = {Aged ; Asbestosis/*complications ; Calcinosis/*etiology ; Humans ; Male ; Middle Aged ; Pleural Diseases/*etiology ; }, abstract = {The presence of calcified pleural plaques together with asbestos professional exposition is the sign of patent dust inhaling and can be related to asbestos pathology. The observations on a homogeneous group of 32 cases of asbestosic pleural calcifications are analyzed. The frequency of malignant pleural and bronchial tumours (2 pleural mesothelioma, 3 bronchial epithelioma) is classical. That there was no serious pulmonary fibrosis can be attributed to the conditions of dust inhaling. There was a relatively high frequency of pleural effusions, the benignity of which could not always be ascertained. Therefore, besides the convincing facts, the precise study of cases with calcified pleural plaques (pleural antecedents, circumstances of the discovery, evolution) could be a rough way of appreciating the frequency of benign asbestos pleurisies.}, } @article {pmid880747, year = {1977}, author = {Rom, W and Anderson, HA}, title = {Case report: malignant mesothelioma.}, journal = {Clinical notes on respiratory diseases}, volume = {16}, number = {1}, pages = {15-16}, pmid = {880747}, issn = {0009-9198}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Environmental Exposure ; Female ; Humans ; Male ; Mesothelioma/*chemically induced ; Occupational Diseases/*chemically induced ; Pleural Neoplasms/*chemically induced ; }, } @article {pmid873540, year = {1977}, author = {Selikoff, IJ}, title = {Air pollution and asbestos carcinogenesis: investigation of possible synergism.}, journal = {IARC scientific publications}, volume = {}, number = {16}, pages = {247-253}, pmid = {873540}, mesh = {Adult ; Air Pollutants/*toxicity ; Air Pollutants, Occupational/*toxicity ; *Air Pollution ; Asbestos/*toxicity ; Canada ; *Cocarcinogenesis ; Drug Synergism ; Female ; Humans ; Lung Neoplasms/etiology/mortality ; Male ; Mesothelioma/etiology/mortality ; Middle Aged ; Neoplasms/*etiology ; Prospective Studies ; Smoking/complications ; United States ; }, } @article {pmid863456, year = {1977}, author = {}, title = {IARC monographs on the evaluation of the carcinogenic risk of chemicals to man: asbestos.}, journal = {IARC monographs on the evaluation of the carcinogenic risk of chemicals to man}, volume = {14}, number = {}, pages = {1-106}, pmid = {863456}, issn = {0301-3944}, mesh = {Air Pollutants/analysis ; Animals ; *Asbestos/analysis/metabolism ; Asbestosis/etiology ; Chemical Phenomena ; Chemistry ; Dental Instruments ; Environmental Exposure ; Humans ; Industry ; Lung Neoplasms/chemically induced ; Mesothelioma/chemically induced ; Molecular Conformation ; Neoplasms/*chemically induced ; Neoplasms, Experimental/chemically induced ; Occupational Medicine ; Peritoneal Neoplasms/chemically induced ; Pleural Neoplasms/chemically induced ; Smoking/complications ; Terminology as Topic ; Trace Elements/analysis ; Water Pollutants/analysis ; }, } @article {pmid844856, year = {1977}, author = {Kannerstein, M and Churg, J}, title = {Peritoneal mesothelioma.}, journal = {Human pathology}, volume = {8}, number = {1}, pages = {83-94}, doi = {10.1016/s0046-8177(77)80067-1}, pmid = {844856}, issn = {0046-8177}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Diagnosis, Differential ; Environmental Exposure ; Female ; Humans ; Male ; Mesothelioma/chemically induced/diagnosis/*pathology ; Middle Aged ; Neoplasm Metastasis ; Peritoneal Neoplasms/chemically induced/diagnosis/*pathology ; Peritoneum/pathology ; }, abstract = {The cytohistology in 82 cases diagnosed as malignant peritoneal mesothelioma was correlated with available clinical and gross pathologic information. The cases were then evaluated as to ceratainty of diagnosis. The material had come from a large number of sources, most of it having been traced by a history of occupational exposure to asbestos. A relatively short interval of significant symptoms, with already existent diffuse peritoneal involvement and ascites, and an average survival time of less than a year characterized the group. The microscopic morphology formed a spectrum from highly characteristic, pure epithelial and mixed epithelial and sarcomatoid types, through nonspecific although relatively differentiated appearances, to pleomorphic analplatic proliferations. Local invasion and metastasis were common but much more limited than with tumors of other histogenesis showing comparable serous membrane involvement. Autopsy was of considerable exclusionary value although not in itself always determinative, and mucopolysaccharide histochemistry was occasionally decisive in diagnosis. Because of the microscopic versatlity of mesothelioma and the clinical and gross morphologic overlap with other neoplasms, all available data must be taken into consideration in arriving at a diagnosis. We believe that the dgree of certainty of diagnosis should be indicated by a succinct but reasonably explicit terminology.}, } @article {pmid842051, year = {1977}, author = {Bittersohl, G}, title = {[The problem of the asbestos induced laryngeal carcinoma].}, journal = {Zeitschrift fur die gesamte Hygiene und ihre Grenzgebiete}, volume = {23}, number = {1}, pages = {27-30}, pmid = {842051}, issn = {0049-8610}, mesh = {Asbestos/*adverse effects ; Environmental Exposure ; Germany, East ; Humans ; Laryngeal Neoplasms/*chemically induced ; Mesothelioma/*chemically induced ; Occupational Diseases/diagnosis ; }, } @article {pmid594007, year = {1977}, author = {Malauzat, C and Petit, MA and Ramaroson, J and Bourzai, M and Gaultier, G}, title = {[Asbestosis. Apropos of one case].}, journal = {Le Poumon et le coeur}, volume = {33}, number = {5}, pages = {321-330}, pmid = {594007}, issn = {0032-5821}, mesh = {Aged ; Asbestosis/*diagnosis/etiology/pathology ; Bronchial Neoplasms/etiology ; Calcinosis/etiology ; Humans ; Lung/pathology ; Lung Neoplasms/etiology ; Male ; Mesothelioma/etiology ; Pleural Neoplasms/etiology ; Pleurisy/etiology ; Pulmonary Fibrosis/etiology ; }, abstract = {Having reported a very complete observation of a patient with asbestosis, as well as silicosis, hitherto undiscovered tuberculosis and a pleural mesothelioma, the authors sum up our present knowledge on the consequences of inhaling asbestos dust. Clinical signs are numerous, benign or malignant, the risks of pleural and broncho-pulmonary cancer being greater in people exposed to asbestos. Diagnosis rests mainly on professional anamnesis and on the presence of great quantities of asbestos bodies in the sputum. Any pleural thickening on X ray should always suggest the development of a mesothelioma. As it now gives right to legal compensation, it is recommended to authentify the malignancy of the thickening by surgery.}, } @article {pmid343534, year = {1977}, author = {Langer, AM and Wolff, MS}, title = {Asbestos carcinogenesis.}, journal = {Advances in experimental medicine and biology}, volume = {91}, number = {}, pages = {29-55}, doi = {10.1007/978-1-4684-0796-9_3}, pmid = {343534}, issn = {0065-2598}, mesh = {Animals ; Asbestos/*adverse effects ; Carcinogens, Environmental ; Carcinoma, Bronchogenic/chemically induced ; Chemical Phenomena ; Chemistry ; Cocarcinogenesis ; Dose-Response Relationship, Drug ; Environmental Exposure ; Humans ; Mesothelioma/chemically induced ; Neoplasms/*chemically induced ; Occupational Diseases/chemically induced ; Particle Size ; Smoking ; Structure-Activity Relationship ; Time Factors ; }, } @article {pmid341238, year = {1977}, author = {Gross, P}, title = {The biologic response to inhaled mineral fibers: facts and fancies.}, journal = {Reviews on environmental health}, volume = {2}, number = {3}, pages = {167-175}, pmid = {341238}, issn = {0048-7554}, mesh = {Animals ; Asbestos ; *Environmental Health ; *Environmental Pollutants ; Female ; *Glass ; Humans ; Lung/pathology ; Male ; Mesothelioma/etiology ; Minerals ; Peritoneal Neoplasms/etiology ; }, } @article {pmid1019298, year = {1976}, author = {Elmes, PC}, title = {Current information on the health risk of asbestos.}, journal = {Royal Society of Health journal}, volume = {96}, number = {6}, pages = {248-252}, pmid = {1019298}, issn = {0035-9130}, mesh = {Asbestos/*adverse effects/metabolism ; Asbestosis/etiology ; Humans ; Lung/physiology ; Lung Neoplasms/chemically induced ; Mesothelioma/chemically induced ; Occupational Diseases/chemically induced ; }, } @article {pmid1076536, year = {1976}, author = {Bakdash, MB and Frydman, A}, title = {Asbestos in periodontal dressings: a possible health hazard.}, journal = {Quintessence international, dental digest}, volume = {7}, number = {10}, pages = {61-65}, pmid = {1076536}, mesh = {Asbestos/*adverse effects ; Asbestosis/*etiology ; Humans ; Mesothelioma/chemically induced ; Periodontal Dressings/*adverse effects ; }, } @article {pmid991095, year = {1976}, author = {Kovarik, JL}, title = {Primary pleural mesothelioma.}, journal = {Cancer}, volume = {38}, number = {4}, pages = {1816-1825}, doi = {10.1002/1097-0142(197610)38:4<1816::aid-cncr2820380459>3.0.co;2-x}, pmid = {991095}, issn = {0008-543X}, mesh = {Aged ; Asbestos/adverse effects ; Female ; Humans ; Male ; Mesothelioma/chemically induced/diagnosis/*pathology/therapy ; Middle Aged ; Pleural Neoplasms/chemically induced/diagnosis/*pathology/therapy ; }, abstract = {In this series of nine patients with primary pleural mesothelioma, three patients, all women, had "localized benign" tumors located in the left chest, although one had a recurrence on the right. Five patients all male, had the "diffuse malignant" type, and one woman had "multiple discrete" pleural tumors. Classification on the basis of gross appearance is useful clinically and prognostically, as reflected by the relatively benign behavior of localized pleural mesothelioma in contrast to the relentless lethal nature of the diffuse type. Although seven patients had pleural effusion, cytologic studies were of little help in establishing the diagnosis and all underwent thoracotomy. None of these patients had hypoglycemia or evidence of asbestosis, although three patients had a history of previous asbestos exposure.}, } @article {pmid981788, year = {1976}, author = {Bischoff, F and Bryson, G}, title = {Toxicologic studies of tin needles at the intrathoracic site of mice.}, journal = {Research communications in chemical pathology and pharmacology}, volume = {15}, number = {2}, pages = {331-340}, pmid = {981788}, issn = {0034-5164}, mesh = {Animals ; Carcinogens ; Female ; Injections ; Kidney/pathology ; Liver/pathology ; Mice ; Particle Size ; Thorax ; Tin/administration & dosage/isolation & purification/*toxicity ; Urinary Bladder/pathology ; }, abstract = {Male Marsh mice which received a single intrathoracic injection of 4 mg of tin needles at 3 months of age were compared with controls given isotonic saline. The form and size of most of the tin needles were similar to those of asbestos needles which produced mesotheliomas and lung neoplasms in rodents. Water and food intake was markedly reduced for 24 hrs after the injection of tin. Survival rates (followed for 19 months), pathology of the bladder, liver, and kidney, as well as local and general cancer development were not adversely associated with the tin treatment as compared with the tin treatment as compared with controls. The local reaction to the tin included giant cell phagocytosis, nodular fibroplasia, and capillary formation. The failure of the tin needles to induce local neoplasms may relate to their high density as compared with silicates and/or their lack of the unique potential of the silicate particles to stimulate avascular fibrosis.}, } @article {pmid970931, year = {1976}, author = {Reeves, AL}, title = {The carcinogenic effect of inhaled asbestos fibers.}, journal = {Annals of clinical and laboratory science}, volume = {6}, number = {5}, pages = {459-466}, pmid = {970931}, issn = {0091-7370}, mesh = {Asbestos/*adverse effects ; Asbestosis/complications ; *Carcinogens, Environmental ; Humans ; Neoplasms/etiology ; }, abstract = {Inhalation of asbestos fibers is associated with high incidence of lung cancers and pleural or peritoneal mesotheliomas in humans. All of these lesions were successfully reproduced in animal experiment, and it was shown that asbestos neoplasm may occur with or without accompanying asbestosis. Incidence of tumors from crocidolite was nearly three times as high as from chrysotile or amosite. It is possible that different carcinogenic entities are responsible for the causation of lung tumors and mesothelial tumors. Lung tumors seem to depend on the adsorptive capacity of asbestos fibers, allowing other carcinogens (heavy metals, polycyclic hydrocarbons, cigarette smoke) to attain a critical focal concentration. Mesothelial tumors, on the other hand, might arise in response to mechanical irritation by fibers which may become lodged during lymphatic spread. Tissues subject to constant respiratory movement (e.g., pleura or peritoneum) are specifically vulnerable to the latter action.}, } @article {pmid1070296, year = {1976}, author = {Das, PB and Fletcher, AG and Deodhare, SG}, title = {Mesothelioma in an agricultural community of India: a clinicopathological study.}, journal = {The Australian and New Zealand journal of surgery}, volume = {46}, number = {3}, pages = {218-226}, doi = {10.1111/j.1445-2197.1976.tb03319.x}, pmid = {1070296}, issn = {0004-8682}, mesh = {Adult ; Agricultural Workers' Diseases/*pathology ; Female ; Humans ; India ; Male ; Mesothelioma/etiology/*pathology/therapy ; Middle Aged ; Neoplasm Metastasis ; Pericardium/*pathology ; Pleura/pathology ; Pleural Neoplasms/etiology/*pathology/therapy ; }, abstract = {Mesothelioma is an uncommon neoplastic condition. Its association with asbestos exposure is well established, but it occurs even in non-industrial workers, and naturally there must be some other factors in its aetiology than asbestos exposure. In this report, five patients with primary mesothelioma, all belonging to a rural agricultural community with no chance of any asbestos exposure, have been documented. There was one common interesting observation, in that all five patients were associated with sugar-cane farming or an allied trade. Whether this observation is coincidental or has any aetiological bearing on mesothelioma needs further investigation. Its histopathological features, symptomatology, diagnosis, and treatment are discussed, with a brief review of the literature.}, } @article {pmid962998, year = {1976}, author = {Newhouse, ML and Berry, G}, title = {Predictions of mortality from mesothelial tumours in asbestos factory workers.}, journal = {British journal of industrial medicine}, volume = {33}, number = {3}, pages = {147-151}, pmid = {962998}, issn = {0007-1072}, mesh = {Asbestos/*adverse effects ; Environmental Exposure ; Female ; Follow-Up Studies ; Humans ; Male ; Mesothelioma/chemically induced/*mortality ; Occupational Diseases/chemically induced/*mortality ; Peritoneal Neoplasms/chemically induced/mortality ; Pleural Neoplasms/chemically induced/mortality ; Prognosis ; Sex Factors ; Time Factors ; }, abstract = {Using the accumulated data on deaths from mesothelial tumours among cohorts of male and female factory workers at a London asbestos textile factory, the mortality from this cause up to the year 2000 AD has been predicted. The limitations of the methods used are pointed out, but it is estimated that for men the mortality due to mesothelial tumours will be between 7% and 11% of the total mortality and somewhat higher for women. The highest number of deaths from mesothelial tumours will occur during the 1980s, thereafter the numbers will decline because of the decreasing size of the cohort resulting from general mortality.}, } @article {pmid185852, year = {1976}, author = {Pott, F and Friedrichs, KH and Huth, F}, title = {[Results of animal experiments concerning the carcinogenic effect of fibrous dusts and their interpretation with regard to the carcinogenesis in humans (author's transl)].}, journal = {Zentralblatt fur Bakteriologie, Parasitenkunde, Infektionskrankheiten und Hygiene. Erste Abteilung Originale. Reihe B: Hygiene, praventive Medizin}, volume = {162}, number = {5-6}, pages = {467-505}, pmid = {185852}, mesh = {Animals ; Asbestos/*toxicity ; Cricetinae ; *Dust ; *Glass ; Guinea Pigs ; Humans ; Magnesium Hydroxide/toxicity ; Mesothelioma/chemically induced/pathology ; Mice ; Neoplasms/*chemically induced/pathology ; Silicic Acid/*toxicity ; Silicon Dioxide/*toxicity ; }, abstract = {After reviewing the hypotheses about the pathogenesis of asbestos-induced malignant tumours we report about experimental data on animals. A high incidence of tumours (most of them mesotheliomas) was induced in rats by intraperitoneal injection of fibrous dusts (chrysotile, palygorscite, crocidolite, glass fibres, nemalite). Treatment with 8 types of granular dusts led though applicating a high dosage (50--100 mg) to neoplasms in only a small percentage of animals. After intraperitoneal application of 2 mg of chrysotile, crocidolite or glass fibres a tumour incidence in a range from 16% to 38% was observed and fibrous reaction was slight. 100 mg of milled chrysotile with relative short fibres (99.8% less than 5 mum, 99.5% less than 3 mum) caused no asbestosis, nevertheless tumours developed in 32% of the rats. Intraperitoneal injection of fibrous dusts also induced mesotheliomas in mice, however not in Syrian hamsters and guinea pigs. Our results point out that the fibrous shape of asbestos dust causes its carcinogenic effect and that furthermore other fibrous dusts can also lead to tumours. Prerequisites are an adequate measure of the fibres and their constancy in the tissue. For these two parameters no exact dates exist. It is estimated that a fibre with a diameter less than 1 mum and a length less than 3 mum exert a cancerogenic effect. Furthermore, a sequence of other factors has an importance for the dose-effect relationship of fibrous dusts. Material of the fibres plays a role in so far it defines the effect producing amount of fibres. The relevance of the results of animal experiments to man is discussed especially with regard to the cancerogenic effect of glass fibres.}, } @article {pmid1276849, year = {1976}, author = {Britton, DC}, title = {Letter: Exposure to asbestos dust.}, journal = {British medical journal}, volume = {2}, number = {6028}, pages = {175}, pmid = {1276849}, issn = {0007-1447}, mesh = {Adult ; Asbestos/*toxicity ; Humans ; Male ; Mesothelioma/*chemically induced ; Peritoneal Neoplasms/*chemically induced ; }, } @article {pmid779552, year = {1976}, author = {Becklake, MR}, title = {Asbestos-related diseases of the lung and other organs: their epidemiology and implications for clinical practice.}, journal = {The American review of respiratory disease}, volume = {114}, number = {1}, pages = {187-227}, doi = {10.1164/arrd.1976.114.1.187}, pmid = {779552}, issn = {0003-0805}, mesh = {Air Pollutants/*toxicity ; Air Pollutants, Occupational/*toxicity ; Asbestos/*toxicity ; *Asbestosis/diagnosis/pathology/physiopathology ; Dose-Response Relationship, Drug ; Gastrointestinal Neoplasms/chemically induced ; Humans ; Lung/physiopathology ; Lung Neoplasms/chemically induced ; Mesothelioma/*chemically induced ; Neoplasms/*chemically induced ; Peritoneal Neoplasms/*chemically induced ; Pleura/pathology ; Pleural Effusion/chemically induced ; Prognosis ; }, } @article {pmid788128, year = {1976}, author = {Bignon, J and Bientz, M and Sébastien, P and Bonnaud, G}, title = {[Asbestos and environment: possible risk of cancer for the general population?].}, journal = {La Revue du praticien}, volume = {26}, number = {33}, pages = {2353-2357}, pmid = {788128}, issn = {0035-2640}, mesh = {Air Pollutants ; *Asbestos ; Asbestosis/epidemiology ; *Carcinogens, Environmental ; Humans ; Lung Neoplasms/epidemiology ; Mesothelioma/epidemiology ; Pleural Neoplasms/epidemiology ; Risk ; Water Pollution, Chemical ; }, } @article {pmid1276690, year = {1976}, author = {}, title = {Editorial: Exposure to asbestos dust.}, journal = {British medical journal}, volume = {1}, number = {6022}, pages = {1361-1362}, pmid = {1276690}, issn = {0007-1447}, mesh = {Asbestos/*adverse effects ; Humans ; Legislation, Medical ; Lung Neoplasms/*chemically induced ; Mesothelioma/*chemically induced ; Occupational Diseases/*chemically induced ; United Kingdom ; }, } @article {pmid1270175, year = {1976}, author = {Embleton, MJ and Wagner, JC and Wagner, MM and Jones, JS and Sheers, G and Oldham, PD and Baldwin, RW}, title = {Assessment of cell-mediated immunity to malignant mesothelioma by microcytotoxicity tests.}, journal = {International journal of cancer}, volume = {17}, number = {5}, pages = {597-601}, doi = {10.1002/ijc.2910170507}, pmid = {1270175}, issn = {0020-7136}, mesh = {Asbestos ; Cells, Cultured ; Cytotoxicity Tests, Immunologic/methods ; Humans ; *Immunity, Cellular ; Mesothelioma/chemically induced/*immunology ; Pleural Effusion/immunology ; Pleural Neoplasms/chemically induced/*immunology ; }, abstract = {Cell cultures were established from pleural effusions of patients with pleural mesothelioma, and peripheral mononuclear effector cells were tested for cytotoxicity against these cells by means of microcytotoxicity assay. Effector cells were obtained from normal healthy donors and from persons exposed occupationally to asbestos, including apparently healthy persons, patients with benign pleural conditions and patients with malignant mesothelioma. The overall incidence of cytotoxicity was low, and there was no evidence of increased cytotoxicity in mesothelioma patients or other asbestos-exposed donors. It is concluded that little or no tumour-directed cell-mediated immunity is detectable against malignant mesothelioma by microcytotoxicity methods.}, } @article {pmid1276091, year = {1976}, author = {Milne, JE}, title = {Thirty-two cases of mesothelioma in Victoria, Australia: a retrospective survey related to occupational asbestos exposure.}, journal = {British journal of industrial medicine}, volume = {33}, number = {2}, pages = {115-122}, pmid = {1276091}, issn = {0007-1072}, mesh = {Adult ; Aged ; Asbestos/*adverse effects/analysis ; Australia ; Female ; Humans ; Lung/analysis ; Male ; Mesothelioma/*epidemiology/genetics ; Middle Aged ; Occupational Diseases/*epidemiology ; Peritoneal Neoplasms/epidemiology/genetics ; Pleural Neoplasms/*epidemiology ; Time Factors ; }, abstract = {Mesotheliomas have been reported in four states in Australia. Crocidolite has been mined and milled at Wittenoom in West Australia where five cases of mesothelioma were reported after exposure of high intensity. The 32 cases of mesothelioma reported in this paper occurred during a period of 11 years in Victoria; 29 were pleural and three peritoneal. There were 22 autopsies. End occupations were misleading in 66% of cases. Two of the three subjects with peritoneal mesothelioma were siblings, and there was no evidence of occupational or other exposure to asbestos in either. There was a significant prevalence of pulmonary asbestos bodies in the tumour series as compared with an unselected consecutive series of 200 routine autopsies (0.01 greater than P greater than 0.001). The occupational history was as effective a method of assessing 'true' asbestos exposure as the pulmonary asbestos body count. Five cases had had a duration of exposure of one year or less, but they had had heavy exposure. The latent interval before tumour development was 25 years or longer in each case. There was no known exposure to asbestos in five cases (16%). The rare association of mesothelioma with types of asbestos other than crocikolite may not exist and could be explicable on the basis of the proportion (16%) of these tumours arising randomly in the population.}, } @article {pmid1276090, year = {1976}, author = {Lumley, KP}, title = {A proportional study of cancer registrations of dockyard workers.}, journal = {British journal of industrial medicine}, volume = {33}, number = {2}, pages = {108-114}, pmid = {1276090}, issn = {0007-1072}, mesh = {Adolescent ; Adult ; Aged ; Asbestos/*adverse effects ; Environmental Exposure ; Gastrointestinal Neoplasms/epidemiology ; Humans ; Male ; Mesothelioma/epidemiology ; Middle Aged ; Neoplasms/*epidemiology ; Occupational Diseases/*epidemiology ; Pleural Neoplasms/epidemiology ; *Ships ; }, abstract = {Evidence of an occupational effect due to asbestos exposure was sought by comparing cancer registrations for dockyard workers with those for Plymouth men in the same age groups for 1960-69. The results show a significant excess of pleural tumours in the dockyard group but no significant excesses at other sites. Registrations for pleural mesothelioma were recorded for men with many dockyard occupations and the observed mean interval between first exposure to asbestos and registration for a pleural tumour (37.6 years) indicates that cases of pleural mesothelioma may be expected to occur among these workers for many years, even though crocidolite is no longer used in naval ships. A trend of increasing annual excess of stomach and gastrointestinal registrations was observed in the dockyard group. No cases of peritoneal mesothelioma were recorded but it is likely that some did occur which were diagnosed as cancers arising from other sites. This may account for some of the excess of gastrointestinal registrations.}, } @article {pmid1046057, year = {1976}, author = {Zeluff, GW and Jenkins, DE and Greenberg, SD}, title = {Asbestos--useful and dangerous.}, journal = {Heart & lung : the journal of critical care}, volume = {5}, number = {3}, pages = {482-484}, pmid = {1046057}, issn = {0147-9563}, mesh = {Aged ; Asbestos/*poisoning ; Asbestosis/*etiology ; Humans ; Male ; Mesothelioma/chemically induced ; Pleural Effusion/chemically induced ; Pleural Neoplasms/chemically induced ; Pulmonary Fibrosis/chemically induced ; }, } @article {pmid57344, year = {1976}, author = {}, title = {Editorial: Asbestos in the air.}, journal = {Lancet (London, England)}, volume = {1}, number = {7966}, pages = {944-945}, pmid = {57344}, issn = {0140-6736}, mesh = {Air Pollutants, Occupational/adverse effects ; Asbestos/adverse effects ; Asbestosis/*prevention & control ; Humans ; *Legislation as Topic ; Mesothelioma/chemically induced ; Occupational Medicine ; United Kingdom ; }, } @article {pmid1279040, year = {1976}, author = {Berry, G and Wagner, JC}, title = {Effect of age at inoculation of asbestos on occurrence of mesotheliomas in rats.}, journal = {International journal of cancer}, volume = {17}, number = {4}, pages = {477-483}, doi = {10.1002/ijc.2910170410}, pmid = {1279040}, issn = {0020-7136}, mesh = {Age Factors ; Animals ; *Asbestos/administration & dosage ; Injections ; Mesothelioma/*chemically induced/mortality/pathology ; Neoplasms, Experimental/chemically induced ; Pleural Neoplasms/*chemically induced/mortality/pathology ; Rats ; Rats, Inbred Strains ; Research Design ; }, abstract = {An experiment in which rats were injected intrapleurally with asbestos, the injection taking place at an age of either 2 or 10 months, is reported. In the former group 19 out of 48 rats developed a mesothelioma compared with 17 out of 90 in the latter group. However, by considering the two groups at equal times after injection, eliminating the effects of natural mortality and also taking into account that not all of the mesotheliomas were the cause of death, it was shown that the incidence rate of mesotheliomas was significantly higher (p less than 0.01) in the rats injected at age 10 months and the relative rate was estimated as about 4, with 95% confidence limits of 1.5 and 12. An alternative explanation that the mesotheliomas occurred in the two groups at similar rates, except that in the group injected at age 10 months they occurred on average 4 months sooner after injection, is discussed. Two other groups were also injected, one at age 17 months and the other at 22 months. In the former group two early mesotheliomas were observed, 10 and 74 days after injection, but the next was not observed until over a year later. No explanation of this finding could be suggested other than the possibility that these two tumours were not associated with the asbestos treatment.}, } @article {pmid1263545, year = {1976}, author = {Shearin, JC and Jackson, D}, title = {Malignant pleural mesothelioma. Report of 19 cases.}, journal = {The Journal of thoracic and cardiovascular surgery}, volume = {71}, number = {4}, pages = {621-627}, pmid = {1263545}, issn = {0022-5223}, mesh = {Adult ; Aged ; Antineoplastic Agents/therapeutic use ; Female ; Humans ; Male ; Mesothelioma/*diagnosis/drug therapy/surgery ; Middle Aged ; Pleural Neoplasms/*diagnosis/drug therapy/surgery ; }, abstract = {Malignant pleural mesothelioma may be composed of sarcomatous, epitheliomatous or mixed cell types. They can be differentiated from localized, benign mesothelioma. Malignant pleural mesothelioma is a rapidly fatal tumor that poses serious diagnostic and therapeutic problems. A series of 19 cases was compiled at the North Carolina Baptist Hospital, and data from these cases were compared to those of other series. The average survival time was 10 months. The most common symptoms were dyspnea, chest pain, pleural effusion, and weight loss. Three patients had a definite history of exposure to asbestos; in 6 more there was a questionable exposure. The most helpful investigative screening tool was the chest roentgenogram, in that it demonstrated an intrathoracic abnormality; however, mesothelioma could not be differentiated from inflammatory reaction or bronchogenic carcinoma with pleural effusion. Sputum cytology as well as pleural effusion cytology was only suggestive of malignancy. Bronchoscopy was not helpful. Needle biopsy yielded malignant cells in 3 of 8 patients. Exploratory thoracotomy was the most accurate means of diagnosis but was frequently followed by seeding into the incision and severe, intractable incisional pain. Therapy proved to be palliative at best. Thoracotomy did not alter the course of the disease; in fact, the production of severe incisional pain was deleterious to the patient's well-being. Cordotomy done in 3 patients brought no relief. Neither radiation therapy nor chemotherapy had a significant effect on survival time or palliation.}, } @article {pmid944540, year = {1976}, author = {Higginson, J}, title = {A hazardous society? Individual versus community responsibility in cancer prevention. Third annual Matthew B. Rosenhaus Lecture.}, journal = {American journal of public health}, volume = {66}, number = {4}, pages = {359-366}, pmid = {944540}, issn = {0090-0036}, mesh = {Asbestos/poisoning ; Environmental Exposure ; Female ; Hemangiosarcoma/chemically induced ; Humans ; Life Style ; Lung Neoplasms/chemically induced ; Male ; Mesothelioma/chemically induced ; Neoplasms/chemically induced/*etiology/prevention & control ; Occupational Diseases/chemically induced ; Risk ; Scrotum ; Smoking/complications ; Social Control, Formal ; Urogenital Neoplasms/chemically induced ; Vinyl Chloride/poisoning ; }, } @article {pmid939216, year = {1976}, author = {Harries, PG}, title = {Experience with asbestos disease and its control in Great Britain's naval dockyards.}, journal = {Environmental research}, volume = {11}, number = {2}, pages = {261-267}, doi = {10.1016/0013-9351(76)90084-0}, pmid = {939216}, issn = {0013-9351}, mesh = {Asbestos/*adverse effects ; Environmental Exposure ; Humans ; Mesothelioma/chemically induced ; Occupational Diseases/*chemically induced ; Occupational Medicine ; Pleural Neoplasms/chemically induced ; Pulmonary Fibrosis/chemically induced ; Respiratory Tract Diseases/*chemically induced/prevention & control ; *Ships ; United Kingdom ; }, } @article {pmid939215, year = {1976}, author = {Edge, JR}, title = {Asbestos related disease in Barrow-in-Furness.}, journal = {Environmental research}, volume = {11}, number = {2}, pages = {244-247}, doi = {10.1016/0013-9351(76)90082-7}, pmid = {939215}, issn = {0013-9351}, mesh = {Asbestos/*adverse effects ; Bronchial Neoplasms/chemically induced/mortality ; England ; Environmental Exposure ; Humans ; Mesothelioma/chemically induced/mortality ; Occupational Diseases/*chemically induced ; Pleural Neoplasms/chemically induced/mortality ; Respiratory Tract Diseases/*chemically induced ; Ships ; }, } @article {pmid1260666, year = {1976}, author = {Fligiel, Z and Kaneko, M}, title = {Malignant mesothelioma of the tunica vaginalis propria testis in a patient with asbestos exposure. A case report.}, journal = {Cancer}, volume = {37}, number = {3}, pages = {1478-1484}, doi = {10.1002/1097-0142(197603)37:3<1478::aid-cncr2820370333>3.0.co;2-g}, pmid = {1260666}, issn = {0008-543X}, mesh = {Aged ; *Asbestos/adverse effects ; Environmental Exposure ; Humans ; Male ; Mesothelioma/chemically induced/*pathology ; Testicular Neoplasms/chemically induced/*pathology ; }, abstract = {A case of malignant mesothelioma arising from the tunica vaginalis propria testis is described. The nature of this tumor is evidenced by in situ malignant change of the mesothelial lining as well as by extensive lymphatic and local tissue invasion. This is the first report of a malignant mesothelioma of the tunica vaginalis associated with asbestos exposure and may be epidemiologically as well as clinically important.}, } @article {pmid970689, year = {1976}, author = {Lajartre, AY and Mussini-Montpellier, J and Lenne, Y}, title = {[Anatomopathologic study of 54 cases of diffuse pleural mesothelioma found in the harbor regions of Nantes, Saint-Nazaire and Lorient].}, journal = {Annales d'anatomie pathologique}, volume = {21}, number = {2}, pages = {247-260}, pmid = {970689}, issn = {0003-3871}, mesh = {Asbestos/adverse effects ; Environmental Exposure ; France ; Humans ; Mesothelioma/chemically induced/*pathology ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Pleura/cytology ; Pleural Neoplasms/chemically induced/*pathology ; }, abstract = {The study concerned the macroscopic and microscopic examination of 54 cases of diffuse malignant mesothelioma. Four points were felt to be of interest and worthy of emphasis: --the unilateral nature of the lesions, constant in this series; --the absence of involvement of other serous surfaces; --the tumour-like appearance of the disorder in 2/3 of cases and the appearance of a simple pachy-pleuritis in 1/3; --from a histological standpoint, despite the morphological flexibility of the classically accepted mesothelial cells, the homogenicity of our group, in which tumour morphology was much more epithelial than histiocytic or connective.}, } @article {pmid970687, year = {1976}, author = {Wagner, JC}, title = {Tumours in experimental animals following exposure to asbestos dust.}, journal = {Annales d'anatomie pathologique}, volume = {21}, number = {2}, pages = {211-214}, pmid = {970687}, issn = {0003-3871}, mesh = {Adenocarcinoma/*chemically induced ; Animals ; *Asbestos ; Carcinoma, Squamous Cell/*chemically induced ; Dust ; Glass ; Mesothelioma/*chemically induced ; Neoplasms, Experimental ; Particle Size ; Pleural Neoplasms/*chemically induced ; Rats ; }, abstract = {The author summarises his research into experimental asbestos-related tumours. He notes in particular the inequality in carcinogenic power of different types of asbestos and the variations in the types of malignant tumour seen (carcinomas or mesotheliomas), according to the variety of asbestos used.}, } @article {pmid970686, year = {1976}, author = {Davis, JM}, title = {Structural variations between pleural and peritoneal mesotheliomas produced in rats by the injection of crocidolite asbestos.}, journal = {Annales d'anatomie pathologique}, volume = {21}, number = {2}, pages = {199-210}, pmid = {970686}, issn = {0003-3871}, mesh = {Adenoma ; Animals ; *Asbestos ; Connective Tissue/ultrastructure ; Connective Tissue Cells ; Epithelial Cells ; Epithelium/ultrastructure ; Mesoderm ; Mesothelioma/chemically induced/*ultrastructure ; Neoplasms, Experimental ; Papilloma ; Peritoneal Neoplasms/chemically induced/*ultrastructure ; Pleural Neoplasms/chemically induced/*ultrastructure ; Rats ; }, abstract = {The author studies the ultrastructure of pleural and peritoneal mesotheliomas caused in the rat by the intra-pleural or intra-peritoneal injection of 25 mg of crocidolite. In the peritoneum the tumour is made up chiefly of "connective" type tissue with rare "epithelial" cells. In the pleura, the "epithelial" cells predominate, constituting vast vegetating "papillomatous" zones or "adenomatous" territories. The author recalls Willis' concept, and feels that mesothelial tumours in the rat, caused by asbestos, represent one aspect of the family of mesenchymatous tumours, with their ability to behave differently according to their site.}, } @article {pmid768710, year = {1976}, author = {Taryle, DA and Lakshminarayan, S and Sahn, SA}, title = {Pleural mesotheliomas--an analysis of 18 cases and review of the literature.}, journal = {Medicine}, volume = {55}, number = {2}, pages = {153-162}, doi = {10.1097/00005792-197603000-00004}, pmid = {768710}, issn = {0025-7974}, mesh = {Adult ; Asbestos/adverse effects ; Carcinoma, Bronchogenic/diagnosis ; Diagnosis, Differential ; Female ; Humans ; Lung Neoplasms/diagnosis ; Male ; Mesothelioma/chemically induced/*diagnosis/diagnostic imaging ; Middle Aged ; Pleural Neoplasms/chemically induced/*diagnosis/diagnostic imaging ; Radiography ; }, abstract = {Eighteen cases of mesothelioma, 7 benign and 11 malignant, were analyzed retrospectively. There were 5 females with benign tumors and 10 males with the malignant variety. The mean age was 59 years in the benign group and 55 years in those with malignant tumors. Exposure to asbestos was documented in one benign and five malignant mesotheliomas. Three patients with benign lesions were asymptomatic on presentation while all 11 with malignant tumors had symptoms, chest pain and dyspnea being the most frequent. Abnormal physical findings were rarely noted in the benign group while all the malignant tumors had abnormal findings on presentation. Signs of a pleural effusion were the most common abnormal physical findings, occurring in 8 of 11 patients. Pleural effusion was the most common roentgenologic finding in malignant mesotheliomas, while a mass lesion was the presenting finding in six of seven of the benign group. Pleural effusion was a usual accompaniment of malignant tumors and was an exudate, usually hemorrhagic with leukocyte counts up to 20,000/mm3. Thoracotomy established the diagnosis in each of the five benign and seven malignant cases in which it was attempted. Pleural biopsy was diagnostic in three of six with malignant and one of two with benign tumors. Pleural fluid cytology did not yield a diagnosis in the seven instances in which it was studied. Excisional surgery was performed in five of the benign cases and all have survived one to six years. No treatment was curative of malignant mesotheliomas. Ten of the 11 with malignant tumors died from 3 to 24 months after onset of symptoms (mean 9.9 months). The clinical features of 82 benign and 160 malignant mesotheliomas from selected series in the literature are reviewed and compared with the present series. The roentgenographic features of 51 benign and 87 malignant tumors are also presented. The clinical and diagnostic features which help differentiate mesotheliomas from bronchogenic carcinomas are discussed. A careful approach to the diagnosis of malignant mesotheliomas may help avoid an unnecessary thoracotomy.}, } @article {pmid184723, year = {1976}, author = {Harington, JS}, title = {The biological effects of mineral fibres, especially asbestos, as seen from in vitro and in vivo studies.}, journal = {Annales d'anatomie pathologique}, volume = {21}, number = {2}, pages = {155-198}, pmid = {184723}, issn = {0003-3871}, mesh = {Animals ; Asbestos/antagonists & inhibitors/*pharmacology/toxicity ; Asbestosis/epidemiology ; Carcinoma, Bronchogenic/chemically induced ; Cell Membrane/drug effects ; Cells, Cultured ; Collagen/biosynthesis ; Erythrocytes/drug effects ; Hemolysis ; Humans ; Lung Neoplasms/chemically induced ; Macrophages/drug effects ; Mesothelioma/chemically induced ; Peritoneal Neoplasms/chemically induced ; Phagocytosis ; Pleural Neoplasms/chemically induced ; Polyvinylpyridine N-Oxide/pharmacology ; Sialic Acids/physiology ; Silicon Dioxide/pharmacology ; }, abstract = {Two in vitro models have been extensively used to compare the biological action of different types of asbestos fibres: the haemolytic effect and the cytotoxic one on macrophages grown in cell culture. The use of both techniques as led towards a better understanding of the chemical reactions which occur between fibres and the biological membranes of cells or intracellular organelles. Studies on the prevention of haemolysis and cytotoxicity have also been of use in explaining how asbestos acts a the cellular and molecular levels. Regarding in vivo studies, useful comparisons have been made of the fibrogenic and carcinogenic effects of different types of fibres in man and experimental animals. Both the in vitro and the in vivo aspects of the problem are discussed in some detail and an attemps is made to provide a reasonably unified concept for both.}, } @article {pmid184542, year = {1976}, author = {Moigneteau, C and Guillement, JM and Touzeau, PY and Pioche, D and Orain, L}, title = {[Effects of asbestos on respiratory pathology. 27 cases observed in 6 years in a pneumo-phthisiology department in Nantes].}, journal = {La semaine des hopitaux : organe fonde par l'Association d'enseignement medical des hopitaux de Paris}, volume = {52}, number = {8}, pages = {467-474}, pmid = {184542}, mesh = {*Asbestosis/diagnosis/diagnostic imaging ; Bronchial Neoplasms/*chemically induced ; Calcinosis/chemically induced ; Humans ; Male ; Mesothelioma/*chemically induced ; Middle Aged ; Pleural Diseases/*chemically induced ; Pleural Neoplasms/*chemically induced ; Radiography ; }, abstract = {A search for respiratory disease due to asbestos permitted the authors, during a review of 6 years' activity on a Chest Unit in Nantes, to collect 27 cases which represents 2.4% of all cases examined. They were male subjects usually aged about 60 years exposed to dust mildly but continuously during a long career as metal workers, mainly in the shipyards. Pleural involvement was constant, usually limited to characteristic pleural calcifications which were well tolerated. Two cases of asbestos pleurisy were diagnosed, but above all we noted 7 cases of mesothelioma with a very poor prognosis. It is difficult to say whether asbestos is responsible for bronchial carcinoma but we noted two cases in patients with calcifications. The authors emphasise the necessity for revision of the table of occupational diseases which does not yet include pleural disease due to asbestos.}, } @article {pmid1274266, year = {1976}, author = {Pylev, LN and Kulagina, TF}, title = {[Mechanism of the induction of asbestos mesotheliomas in the pleura of rats].}, journal = {Voprosy onkologii}, volume = {22}, number = {2}, pages = {63-68}, pmid = {1274266}, issn = {0507-3758}, mesh = {Animals ; *Asbestos ; Benzopyrenes ; Disease Models, Animal ; Female ; Male ; Mesothelioma/*chemically induced ; Pleural Neoplasms/*chemically induced ; Rats ; }, abstract = {The first group of non-bred rats was injected intrapleurally 20 mg of benzene extracted chrysotil-asbestos dust in saline; the second group of rats was injected 20 mg of the same dust but with benz(a)pyrene absorbed on it (0.4 mg). Pleural mesotheliomas were observed in 48.57% of cases in the first group and in 41.37% of cases in the second one. The difference was not significant. There was no difference in the percentage of premesotheliomatous lesions. But, in the second group tumors of other organs were found. The role of asbestos pollution by carcinogenic hydrocarbons in the genesis of lung cancer and pleural mesothelioma is discussed.}, } @article {pmid1069537, year = {1976}, author = {Selikoff, IJ}, title = {Lung cancer and mesothelioma during prospective surveillance of 1249 asbestos insulation workers, 1963-1974.}, journal = {Annals of the New York Academy of Sciences}, volume = {271}, number = {}, pages = {448-456}, doi = {10.1111/j.1749-6632.1976.tb23146.x}, pmid = {1069537}, issn = {0077-8923}, mesh = {Adult ; Aged ; *Asbestos ; Carcinoma, Bronchogenic/chemically induced ; Cocarcinogenesis ; Humans ; Lung Neoplasms/*chemically induced ; Male ; Mesothelioma/*chemically induced ; Middle Aged ; Occupational Diseases/*chemically induced ; Peritoneal Neoplasms/chemically induced ; Pleural Neoplasms/chemically induced ; Prospective Studies ; Smoking/complications ; Time Factors ; }, } @article {pmid1069498, year = {1976}, author = {Nicholson, WJ}, title = {Case study 1: asbestos--the TLV approach.}, journal = {Annals of the New York Academy of Sciences}, volume = {271}, number = {}, pages = {152-169}, doi = {10.1111/j.1749-6632.1976.tb23104.x}, pmid = {1069498}, issn = {0077-8923}, mesh = {Air Pollutants, Occupational ; Asbestos/analysis/*toxicity ; Asbestosis/prevention & control ; Canada ; *Carcinogens, Environmental ; Cocarcinogenesis ; *Environmental Health ; Gastrointestinal Neoplasms/chemically induced ; Humans ; Lung Neoplasms/chemically induced ; Male ; Maximum Allowable Concentration ; Mesothelioma/chemically induced ; Occupational Diseases/chemically induced ; Risk ; Smoking/complications ; Time Factors ; United States ; }, abstract = {A review of the control of carcinogenic exposures using the TLV approach presents a prospect of limited effectiveness. With asbestos, as with any carcinogen, no threshold is known below which no health effect may be manifest. At best, we have only limited dose-response information at levels much above those of practical concern. In the case of asbestos, current exposures can only be described crudely at any level of exposure, and health effects are only known for past high, but ill-defined, exposures. Limited information exists on the effects of synergistic interactions with other materials. The current U.S. TLV, based on data concerned with occurrence of asbestosis, has not been evaluated with regard to possible effectiveness in the prevention of asbestos cancer. Yet cancer is the heart of the asbestos-hazard problem. Finally, enforcement of the existing TLV, especially for asbestos has been limited, frequently absent, and often ineffective. Workers are exposed in many situations to levels much above the current standard. As discouraging as this picture may seem, a TLV can be useful for stimulating the development and application of engineering-control procedures. The application of these procedures, however, must be specified and mandated in future standards to lower worker exposures to the minimum commensurate with existing technology. As technology is developed that makes lower exposure levels possible in a large part of the industry, TLVs should be reduced to take advantage of that technology.}, } @article {pmid1012787, year = {1976}, author = {Bianchi, C and Grandi, G and Di Bonito, L}, title = {[Diffuse mesothelioma of the peritoneum and exposure to asbestos. (Reflections on 2 cases)].}, journal = {Pathologica}, volume = {68}, number = {975-976}, pages = {9-16}, pmid = {1012787}, issn = {0031-2983}, mesh = {Aged ; Asbestos/*adverse effects ; Humans ; Male ; Mesothelioma/*chemically induced/pathology ; Occupational Diseases/*chemically induced ; Peritoneal Neoplasms/*chemically induced/pathology ; }, } @article {pmid1002170, year = {1976}, author = {Jones, JS and Pooley, FD and Smith, PG}, title = {Factory populations exposed to crocidolite asbestos - a continuing survey.}, journal = {IARC scientific publications}, volume = {}, number = {13}, pages = {117-120}, pmid = {1002170}, mesh = {Asbestos/*adverse effects ; Female ; Humans ; Male ; Mesothelioma/*chemically induced ; Occupational Diseases ; Peritoneal Neoplasms/*chemically induced ; Pleural Neoplasms/*chemically induced ; Respiratory Protective Devices ; Time Factors ; }, } @article {pmid1002169, year = {1976}, author = {Gilson, JC}, title = {Asbestos cancers as an example of the problem of comparative risks.}, journal = {IARC scientific publications}, volume = {}, number = {13}, pages = {107-116}, pmid = {1002169}, mesh = {Accidents, Occupational ; Adolescent ; Adult ; Aged ; Animals ; Asbestos/*adverse effects ; Child ; Female ; Humans ; Lung Neoplasms/mortality ; Male ; Mesothelioma/chemically induced/mortality ; Middle Aged ; *Occupational Diseases ; Respiratory Tract Neoplasms/*chemically induced ; Smoking/complications ; }, abstract = {Major differences in excess cancer risks have occurred in the asbestos industry in the past; part of this difference is probably related tp dustiness, part to the type of fibre used. In the case of mesotheliomas there is evidence of a major effect of the fibre type in the order of risk, crocidolite greater than amosite greater than chrysotile greater than anthophyllite. Differences of risk within an industry indicate that there is a dose response relation for both bronchial cancers and mesotheliomas. Also that in some instances it has been possible to identify lightly exposed groups in which no excess risks were detectable. As these least exposed groups are likely to have had several orders of magnitude heavier exposure than the general population, the risks to the general public are likely to be negligible. Bronchial cancers in absolute numbers are the major excess risk and are highly smoking-related. Stopping cigarette smoking is likely to be of paramount importance in reducing the excess cancer risks in asbestos-exposed individuals. Cancers in other sites which may possibly be related to asbestos exposure need further study even though the magnitude of the excess risk has been small compared to the lung cancers. In my view it is now possible to use the epidemiological evidence and experimental results to predict with fair confidence the physical and chemical characters and dose of natural and man-made fibres which will not cause a significant hazard in the future.}, } @article {pmid997423, year = {1976}, author = {Pylev, LN and Kulagina, TF}, title = {[Transplantable strain of pleural mesothelioma (MSh-71) induced by asbestos in rats].}, journal = {Voprosy onkologii}, volume = {22}, number = {8}, pages = {92-95}, pmid = {997423}, issn = {0507-3758}, mesh = {Animals ; *Asbestos ; *Cell Line ; Female ; Male ; Mesothelioma/*chemically induced ; Pleural Neoplasms/*chemically induced ; Rats ; }, } @article {pmid788371, year = {1976}, author = {Beck, B and Irmscher, G}, title = {[Health hazards: asbestos--a review (author's transl)].}, journal = {Zeitschrift fur Erkrankungen der Atmungsorgane}, volume = {144}, number = {2}, pages = {107-128}, pmid = {788371}, issn = {0303-657X}, mesh = {Adolescent ; Adult ; Air Pollution ; Asbestos/*adverse effects ; Asbestosis/epidemiology/etiology ; Canada ; Environmental Health ; Environmental Pollution ; Europe ; Female ; Humans ; Industry ; Lung Neoplasms/chemically induced ; Male ; Mesothelioma/chemically induced ; Middle Aged ; Pleural Diseases/chemically induced ; South Africa ; United States ; }, abstract = {The health hazards caused by asbestos are reviewed and some conclusions are drawn. Asbestos and the materials containing a high percentage of asbestos cannot completely be substituted by other materials without dangerous health effects. It is to be expected that the use of asbestos will still increase. An important health hazard has become evident among asbestos insulation workers. But also in other branches the application of asbestos is widespread. It seems to be difficult to find substitutes meeting the same requirements for using like asbestos. Rock-wool and glass fibres are used more and more in exchange for asbestos. Registers for asbestos workers and asbestos working places are established in several countries. The main causes of death induced by asbestos among asbestos workers are asbestosis. mesothelioma and cancer. For the evaluation and assessment of cancer risk due to asbestos epidemiological studies have to be conducted. Even a short period of exposure to low quantities of asbestos fibres proves to be a health hazard causing certain diseases (diffuse pulmonary fibrosis, pleural hyalinosis, pleural calcifications, mesothelioma) after more than 20 years. For avoiding occupational disease hazards among asbestos workers the dust level on the working place has to be lowered to acceptable concentrations (maximal allowable concentrations). The identification of dust sources of asbestos, the application of practice codes for handling of asbestos, the substitution of asbestos by materials without dangerous health effects, and dust control at source are the most effective directions of hygienic practice. The health protection requires annual medical examinations of all persons exposed to airborne concentrations of asbestos.}, } @article {pmid132768, year = {1976}, author = {Pylev, LN}, title = {[A histochemical study of mesotheliomas of the pleura, induced by asbestos in rats].}, journal = {Voprosy onkologii}, volume = {22}, number = {5}, pages = {53-57}, pmid = {132768}, issn = {0507-3758}, mesh = {Animals ; *Asbestos ; Glycosaminoglycans/metabolism ; Histocytochemistry ; Hyaluronic Acid/metabolism ; Mesothelioma/chemically induced/*metabolism ; Neoplasms, Experimental ; Pleural Neoplasms/chemically induced/*metabolism ; Rats ; }, } @article {pmid63445, year = {1976}, author = {Lawther, PJ and Waller, RE}, title = {Coal fires, industrial emissions and motor vehicles as sources of environmental carcinogens.}, journal = {IARC scientific publications}, volume = {}, number = {13}, pages = {27-40}, pmid = {63445}, mesh = {Air/analysis ; *Air Pollution ; Asbestos/adverse effects ; Benzopyrenes/analysis ; *Carcinogens, Environmental ; Coal ; Fires ; Humans ; Lung Neoplasms/*etiology ; Occupational Diseases ; Smoke ; Smoking/complications ; Sulfur Dioxide/analysis ; United Kingdom ; Urban Population ; Vehicle Emissions ; }, abstract = {One of the most widely studied carcinogenic agents in the environment is the polycyclic hydrocarbon, benzo(a) pyrene. As a component of soot from the inefficient combustion of coal, its association with cancer can be traced back 200 years, but its possible relevance to lung cancer as a widely distributed air relevance to lung cancer as a widely distributed air pollutant has been investigated only during the past 25 years. Domestic coal fires have been shown to be important sources, and smaller amounts come from industrial sources and from motor vehicles. There is evidence now that the concentration of benzo (a) pyrene in large towns in Britain has decreased by a factor of about ten during the last few decades, as a result of changing heating methods and smoke control. In view of the overwhelming effect of cigarette smoking, it is difficult to determine whether the benzo(a)pyrene content of the air has had any importnat effect on the development of lung cancer, but careful analysis of trends in mortality may now throw some light on this. Among other materials with carcinogenic properties that may be dispersed into the general air, asbestos is the one that has been investigated most thoroughly. The association between exposure to asbestos and the development of lung cancer and mesothelioma of the pleura has been clearly demonstrated among people occupationally exposed to the dust, but as far as the general public is concerned, any risk may be limited to the immediate vicinity of major sources. These and other hazards demonstrated among occupational gropus serve as a warning however to maintain careful scutiny of urban air pollutants in relation to the acetiology of cancer.}, } @article {pmid1081808, year = {1975}, author = {Walters, JL and Martinez, AJ}, title = {Malignant fibrous mesothelioma. Metastatic to brain and liver.}, journal = {Acta neuropathologica}, volume = {33}, number = {2}, pages = {173-177}, pmid = {1081808}, issn = {0001-6322}, mesh = {Asbestos/analysis ; Brain Neoplasms/analysis/*pathology ; Cerebellopontine Angle ; Epithelial Cells ; Epithelium/ultrastructure ; Fibroblasts/ultrastructure ; Humans ; Liver Neoplasms/*pathology ; Male ; Mesothelioma/analysis/*pathology ; Middle Aged ; Neoplasm Metastasis/*pathology ; Pleural Neoplasms/analysis/*pathology ; Pons ; }, abstract = {A malignant fibrous mesothelioma in a 52 year old white man arising from the left parietal pleura associated with lupus erythematosus with metastases to brain and liver is reported. Asbestos bodies were found in digested pulmonary tissue but none in the primary or metastatic lesions. Light microscopic and ultrastructural studies suggest that this tumor contains mesothelial or endothelial cells, some of which revealed fibroblastic features while others disclosed epitheloid characteristics.}, } @article {pmid1195924, year = {1975}, author = {}, title = {[All mesothelioma cases in cancer registries are going to be studied].}, journal = {Lakartidningen}, volume = {72}, number = {49}, pages = {4818}, pmid = {1195924}, issn = {0023-7205}, mesh = {*Asbestos ; Mesothelioma/*chemically induced ; Occupational Diseases/*chemically induced ; Occupational Medicine ; Registries ; Sweden ; }, } @article {pmid1205629, year = {1975}, author = {Zielhuis, RL and Versteeg, JP and Planteijdt, HT}, title = {Pleura mesothelioma and exposure to asbestos. A retrospective case-control study in the Netherlands.}, journal = {International archives of occupational and environmental health}, volume = {36}, number = {1}, pages = {1-18}, pmid = {1205629}, issn = {0340-0131}, mesh = {Adult ; Aged ; Asbestos/*poisoning ; Environmental Exposure ; Female ; Humans ; Male ; Mesothelioma/*chemically induced ; Middle Aged ; Netherlands ; Occupational Diseases/*chemically induced ; Pleural Neoplasms/*chemically induced ; Retrospective Studies ; Time Factors ; }, } @article {pmid1234278, year = {1975}, author = {Planteydt, HT}, title = {Disease possibility caused by asbestos.}, journal = {Hefte zur Unfallheilkunde}, volume = {}, number = {126}, pages = {607-609}, doi = {10.1007/978-3-642-95288-3_183}, pmid = {1234278}, issn = {0085-1469}, mesh = {Asbestos/*adverse effects ; Asbestosis/complications ; Humans ; Mesothelioma/chemically induced ; Respiratory Tract Neoplasms/chemically induced ; }, } @article {pmid1234271, year = {1975}, author = {Davis, JM}, title = {The use of animal experiments in the study of asbestos bioeffects.}, journal = {Hefte zur Unfallheilkunde}, volume = {}, number = {126}, pages = {564-574}, doi = {10.1007/978-3-642-95288-3_175}, pmid = {1234271}, issn = {0085-1469}, mesh = {Animals ; Asbestos/adverse effects ; Asbestosis/*physiopathology ; Bronchial Neoplasms/etiology ; Disease Models, Animal ; Humans ; Mesothelioma/etiology ; Neoplasms/etiology ; Rats ; }, } @article {pmid1234269, year = {1975}, author = {Otto, H}, title = {[Mesothelioma and asbestos exposure].}, journal = {Hefte zur Unfallheilkunde}, volume = {}, number = {126}, pages = {555-559}, pmid = {1234269}, issn = {0085-1469}, mesh = {Asbestos/*adverse effects/analysis ; Humans ; Lung Neoplasms/*chemically induced ; Mesothelioma/*chemically induced ; Occupational Diseases/chemically induced ; }, } @article {pmid1234268, year = {1975}, author = {Planteydt, HT}, title = {Mesothelioma and asbestos in the Netherlands.}, journal = {Hefte zur Unfallheilkunde}, volume = {}, number = {126}, pages = {549-555}, doi = {10.1007/978-3-642-95288-3_172}, pmid = {1234268}, issn = {0085-1469}, mesh = {Aged ; Asbestos/*adverse effects ; Female ; Humans ; Mesothelioma/chemically induced/*epidemiology ; Middle Aged ; Netherlands ; Occupational Diseases/chemically induced/epidemiology ; Pleural Neoplasms/chemically induced/*epidemiology ; }, } @article {pmid1234267, year = {1975}, author = {Haider, M and Neuberger, M and Raber, A}, title = {[Mesothelioma cases and asbestos exposure in Austria].}, journal = {Hefte zur Unfallheilkunde}, volume = {}, number = {126}, pages = {547-549}, pmid = {1234267}, issn = {0085-1469}, mesh = {Asbestos/*adverse effects ; Austria ; Humans ; Mesothelioma/chemically induced/*epidemiology ; Occupational Diseases/epidemiology ; Respiratory Tract Neoplasms/chemically induced/*epidemiology ; }, } @article {pmid1234266, year = {1975}, author = {Newhouse, ML}, title = {Asbestos. Smoking, and lung cancer.}, journal = {Hefte zur Unfallheilkunde}, volume = {}, number = {126}, pages = {545-547}, doi = {10.1007/978-3-642-95288-3_170}, pmid = {1234266}, issn = {0085-1469}, mesh = {Asbestos/*adverse effects ; Female ; Humans ; Lung Neoplasms/*chemically induced ; Male ; Mesothelioma/*chemically induced ; Smoking/*complications ; }, } @article {pmid1234264, year = {1975}, author = {Goldstein, B and Webster, I and Harrison, WO and Talent, J}, title = {Epidemiological studies on asbestos-exposed workers in South Africa.}, journal = {Hefte zur Unfallheilkunde}, volume = {}, number = {126}, pages = {538-542}, doi = {10.1007/978-3-642-95288-3_168}, pmid = {1234264}, issn = {0085-1469}, mesh = {Asbestos/adverse effects ; Humans ; Mesothelioma/chemically induced/*epidemiology ; Mining ; Occupational Diseases/*epidemiology ; Respiratory Tract Neoplasms/chemically induced/*epidemiology ; South Africa ; }, } @article {pmid1234263, year = {1975}, author = {Hain, E}, title = {[Current results of epidemiological studies on the asbestos problem in Northern Germany].}, journal = {Hefte zur Unfallheilkunde}, volume = {}, number = {126}, pages = {536-538}, pmid = {1234263}, issn = {0085-1469}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Female ; Gastrointestinal Neoplasms/etiology ; Germany, West ; Humans ; Male ; Mesothelioma/etiology ; Middle Aged ; Neoplasms/epidemiology/*etiology ; Occupational Diseases/epidemiology ; Respiratory Tract Neoplasms/etiology ; }, } @article {pmid1234262, year = {1975}, author = {McDonald, JC and Becklake, MR}, title = {Asbestos-related disease in Canada.}, journal = {Hefte zur Unfallheilkunde}, volume = {}, number = {126}, pages = {521-535}, doi = {10.1007/978-3-642-95288-3_166}, pmid = {1234262}, issn = {0085-1469}, mesh = {Asbestos/adverse effects ; Asbestosis/*epidemiology ; Canada ; Humans ; Mesothelioma/chemically induced ; Occupational Diseases/chemically induced/*epidemiology ; Pulmonary Fibrosis/epidemiology ; Respiratory Tract Neoplasms/chemically induced ; }, } @article {pmid1234260, year = {1975}, author = {Selikoff, IJ}, title = {Epidemiologic investigations of asbestos-exposed workers in the United States.}, journal = {Hefte zur Unfallheilkunde}, volume = {}, number = {126}, pages = {512-520}, doi = {10.1007/978-3-642-95288-3_165}, pmid = {1234260}, issn = {0085-1469}, mesh = {Adult ; Asbestos/adverse effects ; Asbestosis/*epidemiology ; Environmental Exposure ; Humans ; Mesothelioma/etiology ; Middle Aged ; Neoplasms/etiology ; Occupational Diseases/etiology ; Respiratory Tract Neoplasms/etiology ; United States ; }, } @article {pmid1236243, year = {1975}, author = {Wagner, JC and Berry, G and Cooke, TJ and Hill, RJ and Pooley, FD and Skidmore, JW}, title = {Animal experiments with talc.}, journal = {Inhaled particles}, volume = {4 Pt 2}, number = {}, pages = {647-654}, pmid = {1236243}, issn = {0301-1577}, mesh = {Animals ; Female ; Italy ; Male ; Neoplasms/*etiology ; Neoplasms, Experimental/etiology ; Pneumoconiosis/*etiology ; Rats ; Talc/*toxicity ; }, abstract = {Italian talc has been tested on rats using three routes, intra-pleural inoculation, inhalation and ingestion. Groups exposed to superfine chrysotile asbestos and untreated controls were included for comparison. In all the experiments animals were allowed to live out their lives. The intra-pleural inoculation of talc produced no mesotheliomas in contrast to eighteen produced by the chrysotile asbestos. After ingestion, one leiomyosarcoma occurred with Italian talc and one with chrysotile asbestos. Whether these tumours are a consequence of the feeding is uncertain. The inhalation studies demonstrated that with equal dosage, talc can produce a similar amount of fibrosis as asbestos. However, the chrysotile exposed rats developed lung adenomas, adenomatosis and an adenocarcinoma, whereas the only lung tumour seen in animals exposed to talc was a small adenoma, which may have been an incidental finding.}, } @article {pmid1236233, year = {1975}, author = {Sebastien, P and Fondimare, A and Bignon, J and Monchaux, G and Desbordes, J and Bonnaud, G}, title = {Topographic distribution of asbestos fibres in human lung in relation to occupational and non-occupational exposure.}, journal = {Inhaled particles}, volume = {4 Pt 2}, number = {}, pages = {435-446}, pmid = {1236233}, issn = {0301-1577}, mesh = {Adult ; Aged ; Asbestos/*analysis ; Asbestosis/*pathology ; Autopsy ; Female ; Humans ; Lung/*analysis ; Male ; Middle Aged ; Pleura/analysis ; }, abstract = {A topographic study of asbestos fibre content of lung and pleura of diversely exposed cases has been carried out. For heavily exposed cases with lung fibrosis, this study has stressed the distinctive behaviour of the peripheral lower lobe in the retention of asbestos fibres in the lung. In these areas were found the smallest asbestos concentrations but the largest fibres. For cases without lung fibrosis, the results clearly demonstrated an accumulation of asbestos fibres, especially of chrysotile type, in peripheral areas. These findings are to be related to the incidence of pleural mesothelioma associated with moderate or low exposure. The small variation of fibre concentration in the pleural plaques of diversely exposed subjects is pointed out.}, } @article {pmid125920, year = {1975}, author = {Waridel, D and Lanitis, G}, title = {[Localized malignant mesethelioma of the peritoneum revealed by a parietal mass].}, journal = {Schweizerische medizinische Wochenschrift}, volume = {105}, number = {32}, pages = {1026-1030}, pmid = {125920}, issn = {0036-7672}, mesh = {Abdominal Muscles/pathology ; Adult ; Humans ; Lung Neoplasms/surgery ; Male ; Mesothelioma/*diagnosis/pathology/surgery ; Neoplasm Metastasis ; Peritoneal Neoplasms/*diagnosis/pathology/surgery ; Pleural Neoplasms/surgery ; }, abstract = {A report is presented on a rapidly evolving, fatal case of localized malignant mesothelioma of the peritoneum revealed by an abdominal wall mass. Although the tumor was at an advanced stage, a large excision of the primary mass and its metastases was attempted. On the basis of this observation the authors point out the main features of these rare tumors, the diagnostic difficulties they involve, and their possible relationship to asbestos dust exposure.}, } @article {pmid1212398, year = {1975}, author = {Wagner, JC}, title = {Proceedings: Asbestos carcinogenesis.}, journal = {British journal of cancer}, volume = {32}, number = {2}, pages = {258-259}, doi = {10.1038/bjc.1975.206}, pmid = {1212398}, issn = {0007-0920}, mesh = {Animals ; Asbestos/*adverse effects ; Lung Neoplasms/*chemically induced ; Mesothelioma/*chemically induced ; Occupational Diseases/*chemically induced ; Pleural Neoplasms/*chemically induced ; Smoking/complications ; }, } @article {pmid1155847, year = {1975}, author = {Dohner, VA and Beegle, RG and Miller, WT}, title = {Asbestos exposure and multiple primary tumors.}, journal = {The American review of respiratory disease}, volume = {112}, number = {2}, pages = {181-199}, doi = {10.1164/arrd.1975.112.2.181}, pmid = {1155847}, issn = {0003-0805}, mesh = {Adenocarcinoma/epidemiology ; Adenoma/epidemiology ; Aged ; Air Pollutants/*adverse effects ; Air Pollutants, Occupational/*adverse effects ; Asbestos/*adverse effects ; Carcinoma, Bronchogenic/epidemiology ; Carcinoma, Squamous Cell/epidemiology ; Colonic Neoplasms/epidemiology ; Environmental Exposure ; Humans ; Lung/pathology ; Lung Neoplasms/diagnostic imaging/epidemiology/pathology ; Male ; Mesothelioma/epidemiology ; Middle Aged ; Neoplasms, Multiple Primary/*epidemiology ; Occupational Diseases/*chemically induced ; Pleural Neoplasms/epidemiology ; Radiography ; Retrospective Studies ; Smoking/complications ; }, abstract = {Recently we observed 5 patients with multiple primary tumors who also had a history of occupational asbestos exposure. Two patients had a lung carcinoma and a colon carcinoma and 3 others had 2 distinct pulmonary carcinomas. Most of the attending physicians were unaware of the patient's occupational risk for asbestos exposure and the resultant health hazards. Therefore, we review the uses of asbestos and occupations at risk for asbestos exposure.}, } @article {pmid1174793, year = {1975}, author = {Chan, PS and Balfour, TW and Bourke, JB and Smith, PG}, title = {Peritoneal nesothelioma.}, journal = {The British journal of surgery}, volume = {62}, number = {7}, pages = {576-580}, doi = {10.1002/bjs.1800620720}, pmid = {1174793}, issn = {0007-1323}, mesh = {Aged ; Asbestos/adverse effects ; Cholecystitis/complications ; Humans ; Male ; Mesothelioma/complications/*diagnosis/etiology ; Middle Aged ; Peritoneal Neoplasms/*diagnosis/etiology ; }, abstract = {Two patients with primary peritoneal mesothelioma are reported. They had abdominal symptoms, no symptoms referable to the respiratory system and normal chest X-rays. There was no clinical evidence of impaired respiratory function. One of the patients had a history of brief asbestos exposure over 20 years before diagnosis. The procedure for obtaining compensation is outlined and the protean uses of, and hence possible exposure to, asbestos are noted. In screening programmes consideration should be given to both pulmonary and abdominal symptoms. Laparoscopy may have a part to play in earlier diagnosis of peritoneal mesothelioma.}, } @article {pmid1226507, year = {1975}, author = {Nurminen, M}, title = {The epidermiologic relationship between pleural mesothelioma and asbestos exposure.}, journal = {Scandinavian journal of work, environment & health}, volume = {1}, number = {2}, pages = {128-137}, doi = {10.5271/sjweh.2854}, pmid = {1226507}, issn = {0355-3140}, mesh = {Adult ; Age Factors ; Aged ; Asbestos/*poisoning ; Child, Preschool ; Environmental Exposure ; Epidemiologic Methods ; Female ; Finland ; Humans ; Male ; Mesothelioma/*chemically induced/epidemiology ; Middle Aged ; Occupational Diseases/*chemically induced/epidemiology ; Pleural Neoplasms/*chemically induced/epidemiology ; Registries ; Residence Characteristics ; Sex Factors ; }, abstract = {This paper describes an investigation of 85 notifications of either probable or possible mesothelioma to the Finnish Cancer Registry from 1953 through 1969. The investigation covers characteristic epidemiologic features and the possibility of the mesothelioma being connected with occupational or other exposure to asbestos. The incidence rate of pleural mesothelioma was estimated at 1.1 per million per year. The male/female ratio was 1.3:1, which greatly differed fsrom that for malignant neoplasms of the bronchus or lung in Finland in 1960. The mean age at dealth from mesothelioma was over 7 years lower than that for bronchial carcinoma. The ratio of the crude incidence rates for the urban and rural populations was 4.2; the corresponding ratio for cases of carcinoma oopulations was 4.2; the corresponding ratio for cases of carcinoma of the bronchus or lung was 1.2 in Finland in 1960. THE LAST OCCUPATIONS OF THE 82 DECEASED PERSONS, OBTAINED FROM THE DEATH CERTIFICATES, WERE DIVIDIED INTO THREE CATEGORIES ACCORDING TO POSSIBLE ASBESTOS EXPOSURE. Exposure was present or probable in 9 (11.0) cases, 28 (34.2 %) had a possible exposure, and in 33 (40.2 %) cases exposure was absent or unlikely. The occupation of 12 (14.6) persons was unknown. Additional information of possible exposure history was obtained by interviewing the relatives of 10 mesothelioma patients. For half of the persons a definite, although in some cases trivial, exposure to asbestos could be ascertained. For the other five persons no exposure, either occupational, neighborhood or domestic, to asbestos could be traced. The residental distribution of the 85 persons with mesothelioma revealed no clustering of cases.}, } @article {pmid1224688, year = {1975}, author = {Matzel, W and Dann, J}, title = {[Etiology and clinical diagnosis of diffuse pleural mesothelioma (author's transl)].}, journal = {Zeitschrift fur Erkrankungen der Atmungsorgane}, volume = {143}, number = {2}, pages = {97-109}, pmid = {1224688}, issn = {0303-657X}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Endoscopy ; Female ; Germany, East ; Humans ; Male ; Mesothelioma/chemically induced/*diagnosis/pathology ; Middle Aged ; Pleural Effusion/etiology ; Pleural Neoplasms/chemically induced/*diagnosis/pathology ; Punctures ; Respiratory Insufficiency/etiology ; }, abstract = {Diffuse malignant mesothelioma are no longer uncommon diseases within the geographical regions of Halle and Merseburg. These tumors are provoked by the deposition of dust particles of asbestos near the pleura. Asbestos particles are not only obtained by mining and preparation the mineral but also in its use for various purposes - in the past in shipyards mainly and now in the chemical industry as well. The period from the first absorption of these dust particles up to the manifestation of the malignoma is said to last 20-40 years approximately. At present, asbestos is contained in a remarkable great variety of products. Consequently, there is now a general danger, independently of the profession concerned. Possibilities of an exact clinical diagnosis will be discussed on the basis of the experience gained with 100 cases. Only with 17 out of 100 cases the oncogenesis was not accompanied by pleural exudation. The Female/male ratio was 1.0/4.5. 1 - the demonstration of mesothelial cell structures by the transthoracic tumour punctate. 2 - the cytological findings of the effusion cell sediment in connection with the determination of the WELTMANN coagulation band in the effusion and in the blood serum or 3 - the pleuroscopy in connection with the excision of material for cytological and histological tests. A therapeutical treatment is not known till now. Highly restricted use of asbestos is an imperative prophylactic measure.}, } @article {pmid1199211, year = {1975}, author = {Bittersohl, G}, title = {[Epidemiological studies on the incidence and latent time of asbestos-induced hyalinosis, fibrosis and mesothelioma].}, journal = {Zeitschrift fur die gesamte Hygiene und ihre Grenzgebiete}, volume = {21}, number = {5}, pages = {369-371}, pmid = {1199211}, issn = {0049-8610}, mesh = {Adult ; Asbestos/*adverse effects ; Humans ; Lung Diseases/*chemically induced ; Lung Neoplasms/*chemically induced ; Male ; Mesothelioma/*chemically induced ; Pulmonary Fibrosis/*chemically induced ; Time Factors ; }, } @article {pmid1131774, year = {1975}, author = {de Grandpré, L}, title = {[Workers' health is too precious to be a political balloon].}, journal = {Canadian Medical Association journal}, volume = {112}, number = {8}, pages = {999, 1002}, pmid = {1131774}, issn = {0008-4409}, mesh = {Asbestos/adverse effects ; Asbestosis/epidemiology/*prevention & control ; Canada ; Disability Evaluation ; Humans ; Lung Neoplasms/chemically induced ; Mesothelioma/chemically induced ; Occupational Diseases/epidemiology/*prevention & control ; Politics ; Quebec ; }, } @article {pmid1125125, year = {1975}, author = {Doniach, I and Swettenham, KV and Hathorn, MK}, title = {Prevalence of asbestos bodies in a necropsy series in East London: association with disease, occupation, and domiciliary address.}, journal = {British journal of industrial medicine}, volume = {32}, number = {1}, pages = {16-30}, pmid = {1125125}, issn = {0007-1072}, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Asbestos/*analysis ; Asbestosis/complications ; Autopsy ; Breast Neoplasms/chemically induced/epidemiology ; Bronchial Neoplasms/chemically induced/epidemiology ; Female ; Foreign Bodies ; Humans ; London ; Lung/*analysis ; Male ; Middle Aged ; Occupations ; Pleura ; Residence Characteristics ; Sex Factors ; Smoking/complications ; Stomach Neoplasms/chemically induced/epidemiology ; }, abstract = {The prevalence of asbestos bodies was measured in lung sections in a necropsy series carried out at the London Hospital (1965-66) after exclusion of all known asbestos factory workers and cases of asbestosis and of mesothelioma. Associations were sought between the presence and number of asbestos bodies with the patients' sex, domiciliary address, occupation, industry, and diseases recorded at necropsy. Asbestos bodies were present in 42% of the 216 men in the series and in 30% of the 178 women. The number of bodies in the positive cases was small in comparison with the numbers seen typically in asbestosis; thus there were less than 6 asbestos bodies per 6-75 mm-3 lung tissue in 107 of the total 145 positive cases in contrast to 1 000 or more in asbestosis. In comparison with the overall series, an increased number of asbestos body positives was present in males with carcinoma of stomach and females with carcinoma of breast. In view of this finding lung sections were counted in further post-mortem examples of these carcinomas making a total of 50 males with carcinoma stomach and 82 females with carcinoma breast. Thirty-five positive cases were found in the carcinoma stomach group as against 22-7 expected and 38 in the carcinoma breast group against 26-35 expected. There was no excess of observed over expected asbestos body positives in 51 males with carcinoma of bronchus. There was an excess of asbestos body positives (60-9%) in heavy manual workers and in both heavy and light manual male workers in the shipping (61%), electrical and engineering (56%), and transport (54%) industries. The incidence in male clerical workers was 12-8%. The incidence of asbestos body positives according to home address was highest (53% in males, 45% in females) in patients living in the industrial and cockland area due east of the hospital. The incidence fell in the less industrial areas north-east of the hospital. Consideration of possible environmental sources of the inhaled asbestos suggests that in this survey occupation, industry, and comiciliary area all play a part. The comparatively minor intensity of asbestos pollution in our positive cases showed a positive association with carcinoma of stomach and breast, possibly playing a direct pathogenic role in carcinoma of stomach. No positive association was identified with any other neoplastic disease including carcinoma of bronchus.}, } @article {pmid1096586, year = {1975}, author = {}, title = {Background documentation of evaluation of occupational exposure to airborne asbestos.}, journal = {American Industrial Hygiene Association journal}, volume = {36}, number = {2}, pages = {91-103}, doi = {10.1080/0002889758507216}, pmid = {1096586}, issn = {0002-8894}, mesh = {Air Pollution/*analysis ; Asbestos/*analysis/poisoning ; Asbestosis/etiology ; Calcinosis/chemically induced ; Carcinoma, Bronchogenic/chemically induced ; Environmental Exposure ; Evaluation Studies as Topic ; Filtration ; Humans ; Iron ; Lung Neoplasms/*chemically induced ; Maximum Allowable Concentration ; Mesothelioma/chemically induced ; Metalloproteins ; Methods ; Microscopy, Phase-Contrast ; Occupational Diseases/chemically induced ; *Occupational Medicine ; Particle Size ; Peritoneal Neoplasms/chemically induced ; Pleural Diseases/chemically induced ; Pleural Neoplasms/chemically induced ; Statistics as Topic ; }, abstract = {This review presents background information and literature documentation to supplement the "Recommended Procedures for Sampling and Counting Asbestos Fibers: Procedures for the Evaluation of Occupational Exposure to Airborne Asbestos" prepared by the joint ACGIH-AIHA Aerosol Hazards Evaluation Committee. It reviews the nature of the inhalation hazard associated with asbesots fibers, the sampling and analytic methods which have been used, and a rationale for the selection of the membrane filter sampling-optical phase microscope identification and assay methodology which is recommended.}, } @article {pmid163501, year = {1975}, author = {Engelbrecht, FM and Burger, BF}, title = {Mesothelial reaction of asbestos and other irritants after intraperitoneal injection.}, journal = {South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde}, volume = {49}, number = {3}, pages = {87-90}, pmid = {163501}, issn = {0256-9574}, mesh = {Animals ; Asbestos/*toxicity ; Cell Transformation, Neoplastic ; Centrifugation ; Female ; *Glass ; Hydrochloric Acid ; Injections, Intraperitoneal ; Iron/*toxicity ; Mesothelioma/*chemically induced/pathology ; Nitrates ; Oxides/toxicity ; Particle Size ; Peritoneal Neoplasms/*chemically induced/pathology ; Peritoneum/pathology ; Quartz/*toxicity ; Rats ; Silicon Dioxide/*toxicity ; }, abstract = {Ten groups of rats were injected intraperitoneally with one of the following suspensions; (i) standard reference crocidolite; (ii) acid-treated crocidolite (iii) crocidolite plus iron oxide; (iv) crocidolite plus silica; (v) iron oxide; (vi) silica; (vii) long fibre crocidolite; (viii) short fibre crocidolite; (ix) long fibre glass and (x) short fibre glass. Two rats from each group were killed at 45, 90, 150, 240 and 330 days respectively, and the pathology induced by the different suspensions was studied histologically at each time interval. No evidence in support of the chemical induction theory or mechanical irritation theory in the pathogenesis of peritoneal mesotheliomas could be found, although all the suspensions except iron oxide caused a reactive mesothelium.}, } @article {pmid1226869, year = {1975}, author = {Jacob, G}, title = {[Asbestos as an envoronmental carcinogen (author's transl)].}, journal = {Zeitschrift fur Erkrankungen der Atmungsorgane}, volume = {142}, number = {1}, pages = {3-17}, pmid = {1226869}, issn = {0303-657X}, mesh = {Asbestos/*adverse effects ; Asbestosis/*complications/pathology ; Bronchial Neoplasms/epidemiology/etiology ; *Carcinogens, Environmental ; Humans ; Lung/pathology ; Mesothelioma/epidemiology/etiology ; Occupational Diseases ; Occupations ; Peritoneal Neoplasms/*etiology ; Pleural Neoplasms/epidemiology/*etiology ; }, abstract = {Relations between asbestosis and bronchial carcinoma and also since a long time for diffuse malignant pelural and peritoneal mesothelioma have been ascertained for professional exposure to asbestos. On the other hand such relations can be proved statistically for non-professional environmental influence only with malignant serosa tumors. Their increased occurrence goes parallel to the hyaline (calcified) pleura-plaques, to another professional and non-professional consequence of asbestos dust inhalations. There is not enough evidence to accuse asbestos to be a carcinogen causing also other malignomas. It is sure, the number of uncontrolled persons, occupationally or nonoccupationally exposed to asbestos, is still very high. Nevertheless no increased risk of cancer, provoked by asbestos can be supposed for the public at present. For selected population groups, however, increased occurence of mesothelioma cannot be denied, at least in the past. Favorable Favorable conditions exist for the solution of problems still unsolved in asbestosis control, due to the registration of all persons exposed to asbestos dust, and due to the commitment of notifying all tumors.}, } @article {pmid1215750, year = {1975}, author = {Modave, JL and Melange, M and Macq, J and Leblanc, A and Minette, A}, title = {[Reflections on 19 cases of asbestosis discovered by chance in the population of an industrial region in the Basse-Sambre].}, journal = {Revue de l'Institut d'hygiene des mines}, volume = {30}, number = {3}, pages = {111-131}, pmid = {1215750}, issn = {0301-3901}, mesh = {Aged ; Asbestosis/diagnostic imaging/*epidemiology/pathology ; Belgium ; Environmental Exposure ; Female ; Humans ; Male ; Mesothelioma/chemically induced ; Middle Aged ; Occupational Medicine ; Pleural Neoplasms/chemically induced ; Population Surveillance ; Radiography ; }, abstract = {The authors describe 19 cases of definite or highly probable asbestosis which were observed among unselected out-patients at a hospital in the industrial area of the "Basse-Sambre". These cases were of various types and were, almost exclusively, of occupational origin. The variety and severity of the asbestosis in many of the cases justify a more thorough survey in this area. Those people who have handled and inhaled asbestos fibres at work will be examined in the first place. A radiological pulmonary survey will also be organized among the people living in the neighbourhood of factories using asbestos. Precise information about the origin, quality and characteristics of the inhaled dust as well as the intensity and duration of exposure will be obtained. Cases discovered in the survey will be investigated systematically by means of an extensive range of techniques: frontal and oblique X-rays with an appropriate kilovoltage for the detection of pleural calcifications and of the reticular thickening of the parenchyma; spirometry and measurement of the transfer factor for CO; arterial blood gases at rest and during exercise; search for ferruginous bodies in sputum; pathological studies of pulmonary and pleural tissues and of the ultrastructure of pleural tumours.}, } @article {pmid1090086, year = {1975}, author = {Pylev, LN and Iankova, GD}, title = {[Carcinogenic activity of magnesia arfvedsonite (group of amphibole asbestos minerals) administered intrapleurally to nonbred rats].}, journal = {Voprosy onkologii}, volume = {21}, number = {1}, pages = {71-76}, pmid = {1090086}, issn = {0507-3758}, mesh = {Adenofibroma/chemically induced ; Animals ; *Asbestos ; *Carcinogens ; Female ; Hyperplasia ; Lymphatic Diseases/chemically induced ; Lymphoma, Large B-Cell, Diffuse/chemically induced ; Magnesium ; Male ; Mammary Neoplasms, Experimental/chemically induced ; Mesothelioma/chemically induced/pathology ; *Minerals ; Neoplasms, Experimental/*chemically induced ; Pleura ; Pleural Neoplasms/chemically induced/pathology ; Rats ; Silicon ; Time Factors ; USSR ; }, }